Journal: J Am Heart Assoc

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<div><h4>Improvement in Blood Pressure Control in Safety Net Clinics Receiving 2 Versions of a Scalable Quality Improvement Intervention: BP MAP A Pragmatic Cluster Randomized Trial.</h4><i>Fontil V, Modrow MF, Cooper-DeHoff RM, Wozniak G, ... Carton T, Pletcher MJ</i><br /><AbstractText><br /><b>Background:</b><br/>Uncontrolled blood pressure (BP) remains a leading cause of death in the United States. The American Medical Association developed a quality improvement program to improve BP control, but it is unclear how to efficiently implement this program at scale across multiple health systems. Methods and Results We conducted BP MAP (Blood Pressure Measure Accurately, Act Rapidly, and Partner With Patients), a comparative effectiveness trial with clinic-level randomization to compare 2 scalable versions of the quality improvement program: Full Support (with support from quality improvement expert) and Self-Guided (using only online materials). Outcomes were clinic-level BP control (<140/90 mm Hg) and other BP-related process metrics calculated using electronic health record data. Difference-in-differences were used to compare changes in outcomes from baseline to 6 months, between intervention arms, and to a nonrandomized Usual Care arm composed of 18 health systems. A total of 24 safety-net clinics in 9 different health systems underwent randomization and then simultaneous implementation. BP control increased from 56.7% to 59.1% in the Full Support arm, and 62.0% to 63.1% in the Self-Guided arm, whereas BP control dropped slightly from 61.3% to 60.9% in the Usual Care arm. The between-group differences-in-differences were not statistically significant (Full Support versus Self-Guided=+1.2% [95% CI, -3.2% to 5.6%], <i>P</i>=0.59; Full Support versus Usual Care=+3.2% [-0.5% to 6.9%], <i>P</i>=0.09; Self-Guided versus Usual Care=+2.0% [-0.4% to 4.5%], <i>P</i>=0.10). <br /><b>Conclusions:</b><br/>In this randomized trial, 2 methods of implementing a quality improvement intervention in 24 safety net clinics led to modest improvements in BP control that were not statistically significant. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03818659.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e024975; epub ahead of print</small></div>
Fontil V, Modrow MF, Cooper-DeHoff RM, Wozniak G, ... Carton T, Pletcher MJ
J Am Heart Assoc: 25 Jan 2023:e024975; epub ahead of print | PMID: 36695297
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<div><h4>Association Between Duration of Transient Neurological Events and Diffusion-Weighted Brain Lesions.</h4><i>Joundi RA, Yu AYX, Smith EE, Zerna C, ... Coutts SB, SpecTRA Study Group [Link]</i><br /><AbstractText><br /><b>Background:</b><br/>The relationship between duration of transient neurological events and presence of diffusion-weighted lesions by symptom type is unclear. Methods and Results This was a substudy of SpecTRA (Spectrometry for Transient Ischemic Attack Rapid Assessment), a multicenter prospective cohort of patients with minor ischemic cerebrovascular events or stroke mimics at academic emergency departments in Canada. For this study we included patients with resolved symptoms and determined the presence of diffusion-weighted imaging (DWI) lesion on magnetic resonance imaging within 7 days. Using logistic regression, we evaluated the association between symptom duration and DWI lesion, assessing for interaction with symptom type (focal only versus nonfocal/mixed), and adjusting for age, sex, education, comorbidities, and systolic blood pressure. Of 658 patients included, a DWI lesion was present in 232 (35.1%). There was a significant interaction between symptom duration and symptom type. For those with focal-only symptoms, there was a continuous increase in DWI probability up to 24 hours in duration (ranging from ≈40% to 80% probability). In stratified analyses, the increase in probability of DWI lesion with increased duration of focal symptoms was seen in women but not men. For those with nonfocal or mixed symptoms, predicted probability of DWI lesion was ≈35% and was greater in men, but did not increase with longer duration. <br /><b>Conclusions:</b><br/>Increased duration of neurological deficits is associated with greater probability of DWI lesion in those with focal symptoms only. For individuals with nonfocal or mixed symptoms, about one-third had DWI lesions, but the probability did not increase with duration. These results may be important to improve risk stratification of transient neurological events.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e027861; epub ahead of print</small></div>
Joundi RA, Yu AYX, Smith EE, Zerna C, ... Coutts SB, SpecTRA Study Group [Link]
J Am Heart Assoc: 25 Jan 2023:e027861; epub ahead of print | PMID: 36695298
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<div><h4>High Plasma Levels of Soluble Lectin-like Oxidized Low-Density Lipoprotein Receptor-1 Are Associated With Inflammation and Cardiometabolic Risk Profiles in Pediatric Overweight and Obesity.</h4><i>Stinson SE, Jonsson AE, Andersen MK, Lund MAV, ... Holm JC, Hansen T</i><br /><AbstractText><br /><b>Background:</b><br/>Lectin-like oxidized low-density lipoprotein (ox-LDL) receptor-1 is a scavenger receptor for oxidized low-density lipoprotein. In adults, higher soluble lectin-like ox-LDL receptor-1 (sLOX-1) levels are associated with cardiovascular disease, type 2 diabetes, and obesity, but a similar link in pediatric overweight/obesity remains uncertain. Methods and Results Analyses were based on the cross-sectional HOLBAEK Study, including 4- to 19-year-olds from an obesity clinic group with body mass index >90th percentile (n=1815) and from a population-based group (n=2039). Fasting plasma levels of sLOX-1 and inflammatory markers were quantified, cardiometabolic risk profiles were assessed, and linear and logistic regression analyses were performed. Pubertal/postpubertal children and adolescents from the obesity clinic group exhibited higher sLOX-1 levels compared with the population (<i>P</i><0.001). sLOX-1 positively associated with proinflammatory cytokines, matrix metalloproteinases, body mass index SD score, waist SD score, body fat %, plasma alanine aminotransferase, serum high-sensitivity C-reactive protein, plasma low-density lipoprotein cholesterol, triglycerides, systolic and diastolic blood pressure SD score, and inversely associated with plasma high-density lipoprotein cholesterol (all <i>P</i><0.05). sLOX-1 positively associated with high alanine aminotransferase (odds ratio [OR], 1.16, <i>P</i>=4.1 E-04), insulin resistance (OR, 1.16, <i>P</i>=8.6 E-04), dyslipidemia (OR, 1.25, <i>P</i>=1.8 E-07), and hypertension (OR, 1.12, <i>P</i>=0.02). <br /><b>Conclusions:</b><br/>sLOX-1 levels were elevated during and after puberty in children and adolescents with overweight/obesity compared with population-based peers and associated with inflammatory markers and worsened cardiometabolic risk profiles. sLOX-1 may serve as an early marker of cardiometabolic risk and inflammation in pediatric overweight/obesity. Registration The HOLBAEK Study, formerly known as The Danish Childhood Obesity Biobank, ClinicalTrials.gov identifier number NCT00928473, https://clinicaltrials.gov/ct2/show/NCT00928473 (registered June 2009).</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e8145; epub ahead of print</small></div>
Stinson SE, Jonsson AE, Andersen MK, Lund MAV, ... Holm JC, Hansen T
J Am Heart Assoc: 25 Jan 2023:e8145; epub ahead of print | PMID: 36695299
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<div><h4>Phenotyping of Elderly Patients With Heart Failure Focused on Noncardiac Conditions: A Latent Class Analysis From a Multicenter Registry of Patients Hospitalized With Heart Failure.</h4><i>Nakamaru R, Shiraishi Y, Niimi N, Kohno T, ... Kohsaka S, Yoshikawa T</i><br /><AbstractText><br /><b>Background:</b><br/>The burden of noncardiovascular conditions is becoming increasingly prevalent in patients with heart failure (HF). We aimed to identify novel phenogroups incorporating noncardiovascular conditions to facilitate understanding and risk stratification in elderly patients with HF. Methods and Results Data from a total of 1881 (61.2%) patients aged ≥65 years were extracted from a prospective multicenter registry of patients hospitalized for acute HF (N=3072). We constructed subgroups of patients with HF with preserved ejection fraction (HFpEF; N=826, 43.9%) and those with non-HFpEF (N=1055, 56.1%). Latent class analysis was performed in each subgroup using 17 variables focused on noncardiovascular conditions (including comorbidities, Clinical Frailty Scale, and Geriatric Nutritional Risk Index). The latent class analysis revealed 3 distinct clinical phenogroups in both HFpEF and non-HFpEF subgroups: (1) robust physical and nutritional status (Group 1: HFpEF, 41.2%; non-HFpEF, 46.0%); (2) multimorbid patients with renal impairment (Group 2: HFpEF, 40.8%; non-HFpEF, 41.9%); and (3) malnourished patients (Group 3: HFpEF, 18.0%; non-HFpEF, 12.1%). After multivariable adjustment, compared with Group 1, patients in Groups 2 and 3 had a higher risk for all-cause death over the 1-year postdischarge period (hazard ratio [HR], 2.79 [95% CI, 1.64-4.81] and HR, 2.73 [95% CI, 1.39-5.35] in HFpEF; HR, 1.96 [95% CI, 1.22-3.14] and HR, 2.97 [95% CI, 1.64-5.38] in non-HFpEF; respectively). <br /><b>Conclusions:</b><br/>In elderly patients with HF, the phenomapping focused on incorporating noncardiovascular conditions identified 3 phenogroups, each representing distinct clinical outcomes, and the discrimination pattern was similar for both patients with HFpEF and non-HFpEF. This classification provides novel risk stratification and may aid in clinical decision making.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e027689; epub ahead of print</small></div>
Nakamaru R, Shiraishi Y, Niimi N, Kohno T, ... Kohsaka S, Yoshikawa T
J Am Heart Assoc: 25 Jan 2023:e027689; epub ahead of print | PMID: 36695300
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<div><h4>Impact of Achieving Blood Pressure Targets and High Time in Therapeutic Range on Clinical Outcomes in Patients With Atrial Fibrillation Adherent to the Atrial Fibrillation Better Care Pathway: A Report From the COOL-AF Registry.</h4><i>Krittayaphong R, Winijkul A, Methavigul K, Lip GYH</i><br /><AbstractText><br /><b>Background:</b><br/>We aimed to determine the effect of integrating Atrial Fibrillation Better Care pathway compliance in relation to achievement of systolic blood pressure (SBP) targets and good control of time in therapeutic range (TTR) on clinical outcomes in patients with atrial fibrillation. Methods and Results We prospectively enrolled patients with nonvalvular atrial fibrillation  from 27 hospitals in Thailand. All clinical outcomes were recorded. Main outcomes were the composite of all-cause death or ischemic stroke/systemic embolism (SSE), as well as secondary outcomes of all-cause death, SSE, major bleeding, intracranial hemorrhage, and heart failure. An SBP of 120 to 140 mm Hg was considered good blood pressure control. Target TTR was a TTR ≥65%. A total of 3405 patients were studied (mean age 67.8 years, 41.8% female). Full ABC pathway compliance was evident in 42.7%. For blood pressure control, 41.9% had SBP within target, whereas 35.9% of those on warfarin had TTR within target. The incidence rates of all-cause death/SSE, all-cause death, SSE, major bleeding, intracranial hemorrhage, and heart failure were 5.29, 4.21, 1.51, 2.25, 0.78, and 2.84 per 100 person-years respectively. Adjusted hazard ratios and 95% CI of Atrial Fibrillation Better Care pathway compliance for all-cause death/SSE, all-cause death, and heart failure were 0.76 (0.62-0.94), 0.79 (0.62-0.99), and 0.69 (0.51-0.94), respectively, compared with noncompliance. Patients with Atrial Fibrillation Better Care compliance and SBP within target had a better outcome or TTR within target had better outcomes. <br /><b>Conclusions:</b><br/>In COOL-AF (Cohort of Antithrombotic Use and Optimal International Normalized Ratio Level in Patients With Non-Valvular Atrial Fibrillation in Thailand), a multicenter nationwide prospective cohort of patients with atrial fibrillation, achieving SBP within target and TTR ≥ 65% has added value to Atrial Fibrillation Better Care pathway compliance in the reduction of adverse clinical outcomes in patients with atrial fibrillation.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e028463; epub ahead of print</small></div>
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<div><h4>Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function on Cardiovascular Death.</h4><i>Hong D, Lee SH, Shin D, Choi KH, ... Gwon HC, Lee JM</i><br /><AbstractText><br /><b>Background:</b><br/>Coronary microvascular dysfunction (CMD) has been considered as a possible cause of cardiac diastolic dysfunction. The current study evaluated the association between cardiac diastolic dysfunction and CMD, and their prognostic implications in patients without significant left ventricular systolic dysfunction and epicardial coronary stenosis. Methods and Results A total of 330 patients without left ventricular systolic dysfunction (ejection fraction ≥50%) and significant epicardial coronary stenosis (fractional flow reserve >0.80) were analyzed. Cardiac diastolic dysfunction was defined by echocardiographic parameters (early diastolic transmitral flow velocity/early diastolic mitral annular velocity, e\' velocity, tricuspid regurgitation velocity, and left atrial volume index). Overt CMD was defined as coronary flow reserve <2.0 and index of microcirculatory resistance ≥25 U. The primary end point was cardiovascular death or admission for heart failure during 5 years of follow-up. In patients without left ventricular systolic dysfunction and significant epicardial coronary stenosis, prevalence of cardiac diastolic dysfunction and overt CMD was 25.5% and 11.2%, respectively. Overt CMD was independently associated with cardiac diastolic dysfunction (adjusted odds ratio, 3.440 [95% CI, 1.599-7.401]; <i>P</i>=0.002). Patients with cardiac diastolic dysfunction showed significantly higher risk of the primary outcome than those without (adjusted hazard ratio [HR], 2.996 [95% CI, 1.888-4.755]; <i>P</i><0.001). Patients with overt CMD also showed significantly higher risk of the primary outcome than those without (adjusted HR, 2.939 [95% CI, 1.642-5.261]; <i>P</i><0.001). Presence of overt CMD was associated with significantly increased risk of cardiovascular death among the patients with cardiac diastolic dysfunction (43.8% versus 14.5%; <i>P</i>=0.006) but not in patients without cardiac diastolic dysfunction (interaction <i>P</i><0.001). Inclusion of overt CMD into the model with cardiac diastolic dysfunction significantly improved predictive ability for cardiovascular death or heart failure admission (conconrdance index, 0.719 versus 0.737; <i>P</i> for comparison=0.034). <br /><b>Conclusions:</b><br/>There was significant association between the presence of cardiac diastolic dysfunction and overt CMD. Both cardiac diastolic dysfunction and overt CMD were associated with increased risk of cardiovascular death or admission for heart failure. Integration of overt CMD into cardiac diastolic dysfunction showed improvement of the risk stratification in patients without significant left ventricular systolic dysfunction and epicardial coronary stenosis. Registration DIAST-CMD (Prognostic Impact of Cardiac Diastolic Function and Coronary Microvascular Function) registry; Unique identifier: NCT05058833.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e027690; epub ahead of print</small></div>
Hong D, Lee SH, Shin D, Choi KH, ... Gwon HC, Lee JM
J Am Heart Assoc: 25 Jan 2023:e027690; epub ahead of print | PMID: 36695307
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<div><h4>Cardiologic Manifestations in Omicron-Type Versus Wild-Type COVID-19: A Systematic Echocardiographic Study.</h4><i>Ghantous E, Shetrit A, Hochstadt A, Banai A, ... Banai S, Topilsky Y</i><br /><AbstractText><br /><b>Background:</b><br/>Information about the cardiac manifestations of the Omicron variant of COVID-19 is limited. We performed a systematic prospective echocardiographic evaluation of consecutive patients hospitalized with the Omicron variant of COVID-19 infection and compared them with similarly recruited patients were propensity matched with the wild-type variant. Methods and Results A total of 162 consecutive patients hospitalized with Omicron COVID-19 underwent complete echocardiographic evaluation within 24 hours of admission and were compared with propensity-matched patients with the wild-type variant (148 pairs). Echocardiography included left ventricular (LV) systolic and diastolic, right ventricular (RV), strain, and hemodynamic assessment. Echocardiographic parameters during acute infection were compared with historic exams in 62 patients with the Omicron variant and 19 patients with the wild-type variant who had a previous exam within 1 year. Of the patients, 85 (53%) had a normal echocardiogram. The most common cardiac pathology was RV dilatation and dysfunction (33%), followed by elevated LV filling pressure (E/e\' ≥14, 29%) and LV systolic dysfunction (ejection fraction <50%, 10%). Compared with the matched wild-type cohort, patients with Omicron had smaller RV end-systolic areas (9.3±4 versus 12.3±4 cm<sup>2</sup>; <i>P</i>=0.0003), improved RV function (RV fractional-area change, 53.2%±10% versus 39.7%±13% [<i>P</i><0.0001]; RV S\', 12.0±3 versus 10.7±3 cm/s [<i>P</i>=0.001]), and higher stroke volume index (35.6 versus 32.5 mL/m<sup>2</sup>; <i>P</i>=0.004), all possibly related to lower mean pulmonary pressure (34.6±12 versus 41.1±14 mm Hg; <i>P</i>=0.0001) and the pulmonary vascular resistance index (<i>P</i>=0.0003). LV systolic or diastolic parameters were mostly similar to the wild-type variant-matched cohort apart from larger LV size. However, in patients who had a previous echocardiographic exam, these LV abnormalities were recorded before acute Omicron infection, but not in the wild-type cohort. Numerous echocardiographic parameters were associated with higher in-hospital mortality (LV ejection fraction, stroke volume index, E/e\', RV S\'). <br /><b>Conclusions:</b><br/>In patients with Omicron, RV function is impaired to a lower extent compared with the wild-type variant, possibly related to the attenuated pulmonary parenchymal and/or vascular disease. LV systolic and diastolic abnormalities are as common as in the wild-type variant but were usually recorded before acute infection and probably reflect background cardiac morbidity. Numerous LV and RV abnormalities are associated with adverse outcome in patients with Omicron.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e027188; epub ahead of print</small></div>
Ghantous E, Shetrit A, Hochstadt A, Banai A, ... Banai S, Topilsky Y
J Am Heart Assoc: 25 Jan 2023:e027188; epub ahead of print | PMID: 36695308
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<div><h4>Intracranial Hemorrhage Rate and Lesion Burden in Patients With Familial Cerebral Cavernous Malformation.</h4><i>Weinsheimer S, Nelson J, Abla AA, Ko NU, ... Kim H, Brain Vascular Malformation Consortium Cerebral Cavernous Malformation Investigator Group *</i><br /><AbstractText><br /><b>Background:</b><br/>Familial cerebral cavernous alformation (CCM) is an autosomal dominant disease caused by mutations in <i>KRIT1</i>, <i>CCM2</i>, or <i>PDCD10</i>. Cases typically present with multiple lesions, strong family history, and neurological symptoms, including seizures, headaches, or other deficits. Intracranial hemorrhage (ICH) is a severe manifestation of CCM, which can lead to death or long-term neurological deficits. Few studies have reported ICH rates and risk factors in familial CCM. We report ICH rates and assess whether CCM lesion burden, a disease severity marker, is associated with risk of symptomatic ICH during follow-up in a well-characterized cohort of familial CCM cases. Methods and Results We studied 386 patients with familial CCM with follow-up data enrolled in the Brain Vascular Malformation Consortium CCM Project. We estimated symptomatic ICH rates overall and stratified by history of ICH before enrollment. CCM lesion burden (total lesion count and large lesion size) assessed at baseline enrollment was tested for association with increased risk of subsequent ICH during follow-up using Cox regression models adjusted for history of ICH before enrollment, age, sex, and family structure and stratified on recruitment site. The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without (<i>P</i>=0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10-1.71], <i>P</i>=0.006). The symptomatic ICH rate for familial CCM cases was 2.8 per 100 patient-years (95% CI, 1.9-4.1). Those with ICH before enrollment had a follow-up ICH rate of 4.5 per 100 patient-years (95% CI, 2.6-8.1) compared with 2.0 per 100 patient-years (95% CI, 1.3-3.5) in those without (<i>P</i>=0.042). Total lesion count was associated with increased risk of ICH during follow-up (hazard ratio [HR], 1.37 per doubling of total lesion count [95% CI, 1.10-1.71], <i>P</i>=0.006). <br /><b>Conclusions:</b><br/>Patients with familial CCM with prior history of an ICH event are at higher risk for rehemorrhage during follow-up. In addition, total CCM lesion burden is significantly associated with increased risk of subsequent symptomatic ICH; hence lesion burden may be an important predictor of patient outcome and aid patient risk stratification.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e027572; epub ahead of print</small></div>
Weinsheimer S, Nelson J, Abla AA, Ko NU, ... Kim H, Brain Vascular Malformation Consortium Cerebral Cavernous Malformation Investigator Group *
J Am Heart Assoc: 25 Jan 2023:e027572; epub ahead of print | PMID: 36695309
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<div><h4>Cardioprotective Actions of a Glucagon-like Peptide-1 Receptor Agonist on Hearts Donated After Circulatory Death.</h4><i>Kadowaki S, Siraj MA, Chen W, Wang J, ... Husain M, Honjo O</i><br /><AbstractText><br /><b>Background:</b><br/>Heart transplantation with a donation after circulatory death (DCD) heart is complicated by substantial organ ischemia and ischemia-reperfusion injury. Exenatide, a glucagon-like peptide-1 receptor agonist, manifests protection against cardiac ischemia-reperfusion injury in other settings. Here we evaluate the effects of exenatide on DCD hearts in juvenile pigs. Methods and Results DCD hearts with 15-minutes of global warm ischemia after circulatory arrest were reperfused ex vivo and switched to working mode. Treatment with concentration 5-nmol exenatide was given during reperfusion. DCD hearts treated with exenatide showed higher myocardial oxygen consumption (exenatide [n=7] versus controls [n=7], over 60-120 minutes of reperfusion, <i>P</i><0.001) and lower cardiac troponin-I release (27.94±11.17 versus 42.25±11.80 mmol/L, <i>P</i>=0.04) during reperfusion compared with controls. In working mode, exenatide-treated hearts showed better diastolic function (dp/dt min: -3644±620 versus -2193±610 mm Hg/s, <i>P</i><0.001; Tau: 15.62±1.78 versus 24.59±7.35 milliseconds, <i>P</i>=0.02; lateral <i>e</i>\' velocity: 11.27 ± 1.46 versus 7.19±2.96, <i>P</i>=0.01), as well as lower venous lactate levels (3.17±0.75 versus 5.17±1.44 mmol/L, <i>P</i>=0.01) compared with controls. Higher levels of activated endothelial nitric oxide synthase (phosphorylated to total endothelial nitric oxide synthase levels: 2.71±1.16 versus 1.37±0.35, <i>P</i>=0.02) with less histological evidence of endothelial damage (von Willebrand factor expression: 0.024±0.007 versus 0.331±0.302, pixel/μm, <i>P</i>=0.04) was also observed with exenatide treatment versus controls. <br /><b>Conclusions:</b><br/>Acute treatment of DCD hearts with exenatide limits myocardial and endothelial injury and improves donor cardiac function.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e027163; epub ahead of print</small></div>
Kadowaki S, Siraj MA, Chen W, Wang J, ... Husain M, Honjo O
J Am Heart Assoc: 25 Jan 2023:e027163; epub ahead of print | PMID: 36695313
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<div><h4>Body Composition and Risk of Vascular-Metabolic Mortality Risk in 113 000 Mexican Men and Women Without Prior Chronic Disease.</h4><i>Gnatiuc Friedrichs L, Wade R, Alegre-Díaz J, Ramirez-Reyes R, ... Kuri-Morales P, Tapia-Conyer R</i><br /><AbstractText><br /><b>Background:</b><br/>Body-mass index is the sum of fat mass index (FMI) and lean mass index (LMI), which vary by age, sex, and impact on disease outcomes. We investigated the separate and joint relevance of FMI and LMI with vascular-metabolic causes of death in Mexican adults. Methods and Results A total of 113 025 adults aged 35 to 74 years and free from diabetes or other chronic diseases when recruited into the Mexico City Prospective Study were followed for 19 years. Cox models estimated sex-specific death rate ratios from vascular-metabolic causes after adjustment for confounders and exclusion of the first 5 years of follow-up. To account for the strong correlation between FMI and LMI, additional models estimated rate ratios associated with \"residual FMI\" and \"residual LMI\" (ie, the residuals from linear regression analyses of FMI on LMI, or vice versa). In both sexes, higher FMI and LMI were associated with higher risks of vascular-metabolic mortality. For a given (ie, fixed) level of LMI, the rate ratio (95% CI) for vascular-metabolic mortality per 1 kg/m<sup>2</sup> higher residual FMI strengthened and was higher in women (1.52 [1.38-1.68]) than in men (1.19 [1.13-1.25]). By contrast, for a given level of FMI, higher residual LMI was inversely associated with vascular-metabolic mortality (rate ratio per 1 kg/m<sup>2</sup> 0.67 [0.56-0.80] in women and 0.94 [0.90-0.98] in men). <br /><b>Conclusions:</b><br/>In this study, higher residual FMI was more strongly associated with vascular-metabolic mortality in women than in men. Conversely, higher residual LMI was inversely associated with vascular-metabolic mortality, particularly in women.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e028263; epub ahead of print</small></div>
Gnatiuc Friedrichs L, Wade R, Alegre-Díaz J, Ramirez-Reyes R, ... Kuri-Morales P, Tapia-Conyer R
J Am Heart Assoc: 25 Jan 2023:e028263; epub ahead of print | PMID: 36695315
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<div><h4>Influence of Social Determinants of Health on Heart Failure Outcomes: A Systematic Review.</h4><i>Enard KR, Coleman AM, Yakubu RA, Butcher BC, Tao D, Hauptman PJ</i><br /><AbstractText><br /><b>Background:</b><br/>Prior research suggests an association between clinical outcomes in heart failure (HF) and social determinants of health (SDoH). Because providers should identify and address SDoH in care delivery, we evaluated how SDoH have been defined, measured, and evaluated in studies that examine HF outcomes. Methods and Results Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, databases were searched for observational or interventional studies published between 2009 and 2021 that assessed the influence of SDoH on outcomes. Selected articles were assessed for quality using a validated rating scheme. We identified 1373 unique articles for screening; 104 were selected for full-text review, and 59 met the inclusion criteria, including retrospective and prospective cohort, cross-sectional, and intervention studies. The majority examined readmissions and hospitalizations (k=33), mortality or survival (k=29), and success of medical devices and transplantation (k=8). SDoH examined most commonly included race, ethnicity, age, sex, socioeconomic status, and education or health literacy. Studies used a range of 1 to 9 SDoH as primary independent variables and 0 to 7 SDoH as controls. Multiple data sources were employed and frequently were electronic medical records linked with national surveys and disease registries. The effects of SDoH on HF outcomes were inconsistent because of the heterogeneity of data sources and SDoH constructs. <br /><b>Conclusions:</b><br/>Our systematic review reveals shortcomings in measurement and deployment of SDoH variables in HF care. Validated measures need to be prospectively and intentionally collected to facilitate appropriate analysis, reporting, and replication of data across studies and inform the design of appropriate, evidence-based interventions that can ameliorate significant HF morbidity and societal costs.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e026590; epub ahead of print</small></div>
Enard KR, Coleman AM, Yakubu RA, Butcher BC, Tao D, Hauptman PJ
J Am Heart Assoc: 25 Jan 2023:e026590; epub ahead of print | PMID: 36695317
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<div><h4>Dwarf Open Reading Frame (DWORF) Gene Therapy Ameliorated Duchenne Muscular Dystrophy Cardiomyopathy in Aged mdx Mice.</h4><i>Morales ED, Yue Y, Watkins TB, Han J, ... Babu GJ, Duan D</i><br /><AbstractText><br /><b>Background:</b><br/>Cardiomyopathy is a leading health threat in Duchenne muscular dystrophy (DMD). Cytosolic calcium upregulation is implicated in DMD cardiomyopathy. Calcium is primarily removed from the cytosol by the sarcoendoplasmic reticulum calcium ATPase (SERCA). SERCA activity is reduced in DMD. Improving SERCA function may treat DMD cardiomyopathy. Dwarf open reading frame (DWORF) is a recently discovered positive regulator for SERCA, hence, a potential therapeutic target. Methods and Results To study DWORF\'s involvement in DMD cardiomyopathy, we quantified DWORF expression in the heart of wild-type mice and the mdx model of DMD. To test DWORF gene therapy, we engineered and characterized an adeno-associated virus serotype 9-DWORF vector. To determine if this vector can mitigate DMD cardiomyopathy, we delivered it to 6-week-old mdx mice (6×10<sup>12</sup> vector genome particles/mouse) via the tail vein. Exercise capacity, heart histology, and cardiac function were examined at 18 months of age. We found DWORF expression was significantly reduced at the transcript and protein levels in mdx mice. Adeno-associated virus serotype 9-DWORF vector significantly enhanced SERCA activity. Systemic adeno-associated virus serotype 9-DWORF therapy reduced myocardial fibrosis and improved treadmill running, electrocardiography, and heart hemodynamics. <br /><b>Conclusions:</b><br/>Our data suggest that DWORF deficiency contributes to SERCA dysfunction in mdx mice and that DWORF gene therapy holds promise to treat DMD cardiomyopathy.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e027480; epub ahead of print</small></div>
Morales ED, Yue Y, Watkins TB, Han J, ... Babu GJ, Duan D
J Am Heart Assoc: 25 Jan 2023:e027480; epub ahead of print | PMID: 36695318
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<div><h4>Differential Associations of Cystatin C Versus Creatinine-Based Kidney Function With Risks of Cardiovascular Event and Mortality Among South Asian Individuals in the UK Biobank.</h4><i>Chen DC, Lees JS, Lu K, Scherzer R, ... Shlipak MG, Estrella MM</i><br /><AbstractText><br /><b>Background:</b><br/>South Asian individuals have increased cardiovascular disease and mortality risks. Reliance on creatinine- rather than cystatin C-based estimated glomerular filtration rate (eGFRcys) may underestimate the cardiovascular disease risk associated with chronic kidney disease. Methods and Results Among 7738 South Asian UK BioBank participants without prevalent heart failure (HF) or atherosclerotic cardiovascular disease, we investigated associations of 4 eGFRcys and creatinine-based estimated glomerular filtration rate categories (<45, 45-59, 60-89, and ≥90 mL/min per 1.73 m<sup>2</sup>) with risks of all-cause mortality, incident HF, and incident atherosclerotic cardiovascular disease. The mean age was 53±8 years; 4085 (53%) were women. Compared with creatinine, cystatin C identified triple the number of participants with estimated glomerular filtration <45 (n=35 versus n=113) and 6 times the number with estimated glomerular filtration 45 to 59 (n=80 versus n=481). After multivariable adjustment, the eGFRcys 45 to 59 category was associated with higher risks of mortality (hazard ratio [HR], 2.38 [95% CI, 1.55-3.65]) and incident HF (sub-HR [sHR], 1.87 [95% CI, 1.09-3.22]) versus the eGFRcys ≥90 category; the creatinine-based estimated glomerular filtration rate 45 to 59 category had no significant associations with outcomes. Of the 7623 participants with creatinine-based estimated glomerular filtration rate ≥60, 498 (6.5%) were reclassified into eGFRcys <60 categories. Participants who were reclassified as having eGFRcys <45 had higher risks of mortality (HR, 4.88 [95% CI, 2.56-9.31]), incident HF (sHR, 4.96 [95% CI, 2.21-11.16]), and incident atherosclerotic cardiovascular disease (sHR, 2.29 [95% CI, 1.14-4.61]) versus those with eGFRcys ≥90; those reclassified as having eGFRcys 45 to 59 had double the mortality risk (HR, 2.25 [95% CI, 1.45-3.51]). <br /><b>Conclusions:</b><br/>Among South Asian individuals, cystatin C identified a high-risk chronic kidney disease population that was not detected by creatinine and enhanced estimated glomerular filtration rate-based risk stratification for mortality, incident HF, and incident atherosclerotic cardiovascular disease.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e027079; epub ahead of print</small></div>
Chen DC, Lees JS, Lu K, Scherzer R, ... Shlipak MG, Estrella MM
J Am Heart Assoc: 25 Jan 2023:e027079; epub ahead of print | PMID: 36695320
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<div><h4>Trends in Incidences and Survival Rates in Pediatric In-Hospital Cardiopulmonary Resuscitation: A Korean Population-Based Study.</h4><i>Choi J, Choi AY, Park E, Moon S, Son MH, Cho J</i><br /><AbstractText><br /><b>Background:</b><br/>Although the outcome of cardiopulmonary resuscitation (CPR) is still unsatisfactory, there are few studies about temporal trends of in-hospital CPR incidence and mortality. We aimed to evaluate nationwide trends of in-hospital CPR incidence and its associated risk factors and mortality in pediatric patients using a database of the Korean National Health Insurance between 2012 and 2018. Methods and Results We excluded neonates and neonatal intensive care unit admissions. Incidence of in-hospital pediatric CPR was 0.58 per 1000 admissions (3165 CPR/5 429 471 admissions), and the associated mortality was 50.4%. Change in CPR incidence according to year was not significant in an adjusted analysis (<i>P</i>=0.234). However, CPR mortality increased significantly by 6.6% every year in an adjusted analysis (<i>P</i><0.001). Hospitals supporting pediatric critical care showed 37.7% lower odds of CPR incidence (<i>P</i><0.001) and 27.5% lower odds of mortality compared with other hospitals in the adjusted analysis (<i>P</i><0.001), and they did not show an increase in mortality (<i>P</i> for trend=0.882). <br /><b>Conclusions:</b><br/>Temporal trends of in-hospital CPR mortality worsened in Korea, and the trends differed according to subgroups. Study results highlight the need for ongoing evaluation of CPR trends and for further CPR outcome improvement among hospitalized children.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e028171; epub ahead of print</small></div>
Choi J, Choi AY, Park E, Moon S, Son MH, Cho J
J Am Heart Assoc: 25 Jan 2023:e028171; epub ahead of print | PMID: 36695322
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<div><h4>Long-Term Visit-to-Visit Glycemic Variability as a Predictor of Major Adverse Limb and Cardiovascular Events in Patients With Diabetes.</h4><i>Hsu JC, Yang YY, Chuang SL, Huang KC, Lee JK, Lin LY</i><br /><AbstractText><br /><b>Background:</b><br/>Peripheral arterial disease (PAD) is a severe complication in patients with type 2 diabetes. Glycemic variability (GV) is associated with increased risks of developing microvascular and macrovascular diseases. However, few studies have focused on the association between GV and PAD. Methods and Results This cohort study used a database maintained by the National Taiwan University Hospital, a tertiary medical center in Taiwan. For each individual, GV parameters were calculated, including fasting glucose coefficient of variability (FGCV) and hemoglobin A1c variability score (HVS). Multivariate Cox regression models were constructed to estimate the relationships between GV parameters and composite scores for major adverse limb events (MALEs) and major adverse cardiovascular events (MACEs). Between 2014 and 2019, a total of 45 436 adult patients with prevalent type 2 diabetes were enrolled for analysis, and GV was assessed during a median follow-up of 64.4 months. The average number of visits and time periods were 13.38 and 157.87 days for the HVS group and 14.27 and 146.59 days for the FGCV group, respectively. The incidence rates for cardiac mortality, PAD, and critical limb ischemia (CLI) were 5.38, 20.11, and 2.41 per 1000 person-years in the FGCV group and 5.35, 20.32, and 2.50 per 1000 person-years in HVS group, respectively. In the Cox regression model with full adjustment, the highest FGCV quartile was associated with significantly increased risks of MALEs (hazard ratio [HR], 1.57 [95% CI, 1.40-1.76]; <i>P</i><0.001) and MACEs (HR, 1.40 [95% CI, 1.25-1.56]; <i>P</i><0.001). Similarly, the highest HVS quartile was associated with significantly increased risks of MALEs (HR, 1.44 [95% CI, 1.28-1.62]; <i>P</i><0.001) and MACEs (HR, 1.28 [95% CI, 1.14-1.43]; <i>P</i><0.001). The highest FGCV and HVS quartiles were both associated with the development of PAD and CLI (FGCV: PAD [HR, 1.57; <i>P</i><0.001], CLI [HR, 2.19; <i>P</i><0.001]; HVS: PAD [HR, 1.44; <i>P</i><0.001], CLI [HR, 1.67; <i>P</i>=0.003]). The Kaplan-Meier analysis showed significantly higher risks of MALEs and MACEs with increasing GV magnitude (log-rank <i>P</i><0.001). <br /><b>Conclusions:</b><br/>Among individuals with diabetes, increased GV is independently associated with the development of MALEs, including PAD and CLI, and MACEs. The benefit of maintaining stable glycemic levels for improving clinical outcomes warrants further studies.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e025438; epub ahead of print</small></div>
Hsu JC, Yang YY, Chuang SL, Huang KC, Lee JK, Lin LY
J Am Heart Assoc: 25 Jan 2023:e025438; epub ahead of print | PMID: 36695326
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<div><h4>Stroke Recurrence Following 28 Days After First Stroke in Men and Women 2012 to 2020: Observations From the Swedish Stroke Register.</h4><i>Eriksson M, Grundberg A, Inge E, von Euler M</i><br /><AbstractText><br /><b>Background:</b><br/>Stroke incidence, care, and survival show continuous improvements in Sweden, including no or decreasing disparities between men and women. In this study, we aimed to estimate and compare the risk of stroke recurrence in men and women over time, accounting for the competing risk of death. Methods and Results We included adult patients with first-time stroke (ischemic or intracerebral hemorrhage) registered in Riksstroke (the Swedish Stroke Register), 2012 to 2020, and followed until December 2020. Stroke recurrences included new events registered in Riksstroke from 28 days after stroke. To account for the competing risk of death, we used the cumulative incidence function to estimate crude incidences, and multivariable Cox regression to estimate cause-specific hazard ratios (HRs) adjusting for differences in patients\' risk factor profiles. The study included 72 148 (53.5%) men and 62 689 (46.5%) women. We observed 10 925 stroke recurrences and 81 811 deaths following the initial 28 days after the first stroke. The cumulative incidence of stroke recurrence was 3.7% (95% CI, 3.6-3.8) after 1 year, 7.0 (95% CI, 6.8-7.1) after 3 years, and 9.1% (95% CI, 8.9-9.3) after 5 years. The incidence decreased substantially during the study period (HR, 2019-2020 versus 2012, 0.824 [95% CI, 0.759-0.894]). Overall, men had a lower risk of stroke recurrence. After adjustments for differences in patient characteristics, men had a slightly higher risk of recurrence (of any type) after an ischemic stroke (HR, 1.090 [95% CI, 1.045-1.138]) and a lower risk after hemorrhagic stroke (HR, 0.880 [95% CI, 0.781-0.991]) compared with women. <br /><b>Conclusions:</b><br/>The risk of stroke recurrence has decreased in both men and women. Women\'s higher age and other differences in risk factors partly explain their higher risk of stroke recurrence compared with men.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Jan 2023:e028222; epub ahead of print</small></div>
Eriksson M, Grundberg A, Inge E, von Euler M
J Am Heart Assoc: 23 Jan 2023:e028222; epub ahead of print | PMID: 36688356
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<div><h4>Magnetic Resonance Imaging-Derived Microvascular Perfusion Modeling to Assess Peripheral Artery Disease.</h4><i>Gimnich OA, Belousova T, Short CM, Taylor AA, ... Shah DJ, Brunner G</i><br /><AbstractText><br /><b>Background:</b><br/>Computational fluid dynamics has shown good agreement with contrast-enhanced magnetic resonance imaging measurements in cardiovascular disease applications. We have developed a biomechanical model of microvascular perfusion using contrast-enhanced magnetic resonance imaging signal intensities derived from skeletal calf muscles to study peripheral artery disease (PAD). Methods and Results The computational microvascular model was used to study skeletal calf muscle perfusion in 56 individuals (36 patients with PAD, 20 matched controls). The recruited participants underwent contrast-enhanced magnetic resonance imaging and ankle-brachial index testing at rest and after 6-minute treadmill walking. We have determined associations of microvascular model parameters including the transfer rate constant, a measure of vascular leakiness; the interstitial permeability to fluid flow which reflects the permeability of the microvasculature; porosity, a measure of the fraction of the extracellular space; the outflow filtration coefficient; and the microvascular pressure with known markers of patients with PAD. Transfer rate constant, interstitial permeability to fluid flow, and microvascular pressure were higher, whereas porosity and outflow filtration coefficient were lower in patients with PAD than those in matched controls (all <i>P</i> values ≤0.014). In pooled analyses of all participants, the model parameters (transfer rate constant, interstitial permeability to fluid flow, porosity, outflow filtration coefficient, microvascular pressure) were significantly associated with the resting and exercise ankle-brachial indexes, claudication onset time, and peak walking time (all <i>P</i> values ≤0.013). Among patients with PAD, interstitial permeability to fluid flow, and microvascular pressure were higher, while porosity and outflow filtration coefficient were lower in treadmill noncompleters compared with treadmill completers (all <i>P</i> values ≤0.001). <br /><b>Conclusions:</b><br/>Computational microvascular model parameters differed significantly between patients with PAD and matched controls. Thus, computational microvascular modeling could be of interest in studying lower extremity ischemia.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Jan 2023:e027649; epub ahead of print</small></div>
Gimnich OA, Belousova T, Short CM, Taylor AA, ... Shah DJ, Brunner G
J Am Heart Assoc: 23 Jan 2023:e027649; epub ahead of print | PMID: 36688362
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<div><h4>Real-World Disparities in Remote Follow-Up of Cardiac Implantable Electronic Devices and Impact of the COVID-19 Pandemic: A Single-Center Experience.</h4><i>Lehmann HI, Sharma K, Bhatia R, Mills T, ... Singh J, Mela T</i><br /><AbstractText><br /><b>Background:</b><br/>Remote monitoring (RM) of cardiac implantable electronic devices has been shown to improve cardiovascular morbidity and mortality. To date, no studies have investigated disparities in use and delivery of RM. This study was performed to investigate if racial and socioeconomic disparities are present in cardiac implantable electronic device RM. Methods and Results This was a retrospective observational cohort study at a single tertiary care center in the United States. Patients who received a newly implanted cardiac implantable electronic device or device upgrade between January 2017 and December 2020 were included. Patients were classified as RM positive (RM+) when they underwent at least ≥2 remote interrogations per year during follow-up. Of all eligible patients, 2520 patients were included, and 34% were women. The mean follow-up was 25 months. Mean age was 71±14 years. Pacemakers constituted 66% of implanted devices, whereas 26% were implantable cardioverter-defibrillators, and 8% were cardiac resynchronization therapy with implantable cardioverter-defibrillators. Most patients (83%) were of European American ancestry. During follow-up, 66% of patients were classified as RM+. Patients who were younger, European American, college-educated, lived in a county with higher median household income, and were active on the hospital\'s patient portals were more frequently RM+. In an adjusted regression model, RM+ remained associated with the use of the online patient portal (odds ratio [OR], 2.889 [95% CI, 2.387-3.497]), presence of an implantable cardioverter-defibrillator (OR, 1.489 [95% CI, 1.207-1.835]), advanced college degree (OR, 1.244 [95% CI, 1.014-1.527]), and lastly with European American ancestry (<i>P</i><0.05). During the years of the COVID-19 pandemic, the number of RM+ patients increased, whereas the association with ancestry and ethnicity decreased. <br /><b>Conclusions:</b><br/>Despite being offered to all patients at implantation, significant disparities were present in cardiovascular implantable electronic device RM in this cohort. Disparities were partly reversed during COVID-19. Further studies are needed to examine health center- and patient-specific factors to overcome these barriers, and to facilitate equal opportunities to participate in RM.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Jan 2023:e027500; epub ahead of print</small></div>
Lehmann HI, Sharma K, Bhatia R, Mills T, ... Singh J, Mela T
J Am Heart Assoc: 23 Jan 2023:e027500; epub ahead of print | PMID: 36688364
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<div><h4>Association of Depression and Poor Mental Health With Cardiovascular Disease and Suboptimal Cardiovascular Health Among Young Adults in the United States.</h4><i>Kwapong YA, Boakye E, Khan SS, Honigberg MC, ... Blaha MJ, Sharma G</i><br /><AbstractText><br /><b>Background:</b><br/>Depression is a nontraditional risk factor for cardiovascular disease (CVD). Data on the association of depression and poor mental health with CVD and suboptimal cardiovascular health (CVH) among young adults are limited. Methods and Results We used data from 593 616 young adults (aged 18-49 years) from the 2017 to 2020 Behavioral Risk Factor Surveillance System, a nationally representative survey of noninstitutionalized US adults. Exposures were self-reported depression and poor mental health days (PMHDs; categorized as 0, 1-13, and 14-30 days of poor mental health in the past 30 days). Outcomes were self-reported CVD (composite of myocardial infarction, angina, or stroke) and suboptimal CVH (≥2 cardiovascular risk factors: hypertension, hypercholesterolemia, overweight/obesity, smoking, diabetes, physical inactivity, and inadequate fruit and vegetable intake). Using logistic regression, we investigated the association of depression and PMHDs with CVD and suboptimal CVH, adjusting for sociodemographic factors (and cardiovascular risk factors for the CVD outcome). Of the 593 616 participants (mean age, 34.7±9.0 years), the weighted prevalence of depression was 19.6% (95% CI, 19.4-19.8), and the weighted prevalence of CVD was 2.5% (95% CI, 2.4-2.6). People with depression had higher odds of CVD than those without depression (odds ratio [OR], 2.32 [95% CI, 2.13-2.51]). There was a graded association of PMHDs with CVD. Compared with individuals with 0 PMHDs, the odds of CVD in those with 1 to 13 PMHDs and 14 to 30 PHMDs were 1.48 (95% CI, 1.34-1.62) and 2.29 (95% CI, 2.08-2.51), respectively, after adjusting for sociodemographic and cardiovascular risk factors. The associations did not differ significantly by sex or urban/rural status. Individuals with depression had higher odds of suboptimal CVH (OR, 1.79 [95% CI, 1.65-1.95]) compared with those without depression, with a similar graded relationship between PMHDs and suboptimal CVH. <br /><b>Conclusions:</b><br/>Depression and poor mental health are associated with premature CVD and suboptimal CVH among young adults. Although this association is likely bidirectional, prioritizing mental health may help reduce CVD risk and improve CVH in young adults.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Jan 2023:e028332; epub ahead of print</small></div>
Kwapong YA, Boakye E, Khan SS, Honigberg MC, ... Blaha MJ, Sharma G
J Am Heart Assoc: 23 Jan 2023:e028332; epub ahead of print | PMID: 36688365
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<div><h4>Effects of Ablation Versus Drug Therapy on Quality of Life by Sex in Atrial Fibrillation: Results From the CABANA Trial.</h4><i>Zeitler EP, Li Y, Silverstein AP, Russo AM, ... Mark DB, CABANA Investigators</i><br /><AbstractText><br /><b>Background:</b><br/>Women with atrial fibrillation (AF) demonstrate more AF-related symptoms and worse quality of life (QOL). Whether increased use of ablation in women reduces sex-related QOL differences is unknown. Sex-related outcomes for ablation versus drug therapy was a prespecified analysis in the CABANA (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) trial. Methods and Results Symptoms were assessed periodically over 60 months with the Mayo AF-Specific Symptom Inventory (MAFSI) frequency score, and QOL was assessed with the Atrial Fibrillation Effect on Quality of Life (AFEQT) summary and component scores. Women had lower baseline QOL scores than men (mean AFEQT scores 55.9 and 65.6, respectively). Ablation patients improved more than drug therapy patients with similar treatment effect by sex: AFEQT 12-month mean adjusted treatment difference in women 6.1 points (95% CI, 3.5-8.6) and men 4.9 points (95% CI, 3.0-6.9). Participants with baseline AFEQT summary scores <70 had greater QOL improvement, with a mean treatment difference at 12 months of 7.6 points for women (95% CI, 4.3-10.9) and 6.4 points for men (95% CI, 3.3-9.4). The mean adjusted difference in MAFSI frequency score between women randomized to ablation versus drug therapy at 12 months was -2.5 (95% CI, -3.4 to -1.6); for men, the difference was -1.3 (95% CI, -2.0 to -0.6). <br /><b>Conclusions:</b><br/>Compared with drug therapy for AF, ablation resulted in more QOL improvement in both sexes, primarily driven by improvements in those with lower baseline QOL. Ablation did not eliminate the AF-related QOL gap between women and men. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00911508.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Jan 2023:e027871; epub ahead of print</small></div>
Zeitler EP, Li Y, Silverstein AP, Russo AM, ... Mark DB, CABANA Investigators
J Am Heart Assoc: 23 Jan 2023:e027871; epub ahead of print | PMID: 36688367
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<div><h4>Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 Inhibition in Type 2 Diabetes: Phase 1 Results.</h4><i>Vavere AL, Sinsakul M, Ongstad EL, Yang Y, ... Gupta R, George RT</i><br /><AbstractText><br /><b>Background:</b><br/>Blockade of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a potentially attractive mechanism for lowering inflammatory and lipid risk in patients with atherosclerosis. This study aims to assess the safety, tolerability, and target engagement of MEDI6570, a high-affinity monoclonal blocking antibody to LOX-1. Methods and Results This phase 1, first-in-human, placebo-controlled study (NCT03654313) randomized 88 patients with type 2 diabetes to receive single ascending doses (10, 30, 90, 250, or 500 mg) or multiple ascending doses (90, 150, or 250 mg once monthly for 3 months) of MEDI6570 or placebo. Primary end point was safety; secondary and exploratory end points included pharmacokinetics, immunogenicity, free soluble LOX-1 levels, and change in coronary plaque volume. Mean age was 57.6/58.1 years in the single ascending doses/multiple ascending doses groups, 31.3%/62.5% were female, and mean type 2 diabetes duration was 9.7/8.7 years. Incidence of adverse events was similar among cohorts. MEDI6570 exhibited nonlinear pharmacokinetics, with terminal half-life increasing from 4.6 days (30 mg) to 11.2 days (500 mg), consistent with target-mediated drug disposition. Dose-dependent reductions in mean soluble LOX-1 levels from baseline were observed (>66% at 4 weeks and 71.61-82.96% at 10 weeks in the single ascending doses and multiple ascending doses groups, respectively). After 3 doses, MEDI6570 was associated with nonsignificant regression of noncalcified plaque volume versus placebo (-13.45 mm<sup>3</sup> versus -8.25 mm<sup>3</sup>). <br /><b>Conclusions:</b><br/>MEDI6570 was well tolerated and demonstrated dose-dependent soluble LOX-1 suppression and a pharmacokinetic profile consistent with once-monthly dosing. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT03654313.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Jan 2023:e027540; epub ahead of print</small></div>
Vavere AL, Sinsakul M, Ongstad EL, Yang Y, ... Gupta R, George RT
J Am Heart Assoc: 23 Jan 2023:e027540; epub ahead of print | PMID: 36688371
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<div><h4>Prognostic Implication of Mitral Valve Disease and Its Progression in East Asian Patients With Hypertrophic Cardiomyopathy.</h4><i>Kim DY, Seo J, Cho I, Hong GR, Ha JW, Shim CY</i><br /><AbstractText><br /><b>Background:</b><br/>Hypertrophic cardiomyopathy (HCM) is a genetic disorder affecting not only the myocardium but also the mitral valve (MV) and its apparatus. This study aimed to investigate the prognostic implication of MV disease and its progression in East Asian patients with HCM. Methods and Results We assessed MV structure and function on the indexed echocardiogram of 1185 patients with HCM (mean±SD age, 60±14 years; men, 67%) in a longitudinal HCM registry, and 667 patients who performed follow-up echocardiogram after 3 to 5 years were also analyzed. Progression of mitral regurgitation (MR) was defined as the increase of at least 1 grade. Clinical outcomes were defined as a composite of cardiovascular death, heart failure hospitalization, MV surgery or septal myectomy, and heart transplantation. Most of the entire cohort was nonobstructive type (n=1081 [91.2%]). A total of 278 patients (23.5%) showed at least mild MR on indexed echocardiogram. MR, systolic anterior motion, and mitral annular calcification were more prevalent in patients with obstructive HCM. During 7.0±4.0 years of follow-up, presence of MR was independently associated with poor clinical outcomes (hazard ratio [HR], 1.60 [95% CI, 1.07-2.40]; <i>P</i>=0.023). On follow-up echocardiogram, 67 (10.0%) patients showed MR progression, and it was independently associated with poor prognosis (HR, 2.46 [95% CI, 1.29-4.71]; <i>P</i>=0.007). <br /><b>Conclusions:</b><br/>In East Asian patients with HCM whose major type is nonobstructive, MV disease is common. MR, systolic anterior motion, and mitral annular calcification are more prevalent in patients with obstructive HCM. The presence and progression of MR are associated with a poor prognosis in patients with HCM.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 23 Jan 2023:e024792; epub ahead of print</small></div>
Kim DY, Seo J, Cho I, Hong GR, Ha JW, Shim CY
J Am Heart Assoc: 23 Jan 2023:e024792; epub ahead of print | PMID: 36688372
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<div><h4>Association of Eating and Sleeping Intervals With Weight Change Over Time: The Daily24 Cohort.</h4><i>Zhao D, Guallar E, Woolf TB, Martin L, ... Clark JM, Bennett WL</i><br /><AbstractText><br /><b>Background:</b><br/>We aim to evaluate the association between meal intervals and weight trajectory among adults from a clinical cohort. Methods and Results This is a multisite prospective cohort study of adults recruited from 3 health systems. Over the 6-month study period, 547 participants downloaded and used a mobile application to record the timing of meals and sleep for at least 1 day. We obtained information on weight and comorbidities at each outpatient visit from electronic health records for up to 10  years before until 10 months after baseline. We used mixed linear regression to model weight trajectories. Mean age was 51.1 (SD 15.0) years, and body mass index was 30.8 (SD 7.8) kg/m<sup>2</sup>; 77.9% were women, and 77.5% reported White race. Mean interval from first to last meal was 11.5 (2.3) hours and was not associated with weight change. The number of meals per day was positively associated with weight change. The average difference in annual weight change (95% CI) associated with an increase of 1 daily meal was 0.28 kg (0.02-0.53). <br /><b>Conclusions:</b><br/>Number of daily meals was positively associated with weight change over 6 years. Our findings did not support the use of time-restricted eating as a strategy for long-term weight loss in a general medical population.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 18 Jan 2023:e026484; epub ahead of print</small></div>
Zhao D, Guallar E, Woolf TB, Martin L, ... Clark JM, Bennett WL
J Am Heart Assoc: 18 Jan 2023:e026484; epub ahead of print | PMID: 36651320
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<div><h4>Developmental Care for Hospitalized Infants With Complex Congenital Heart Disease: A Science Advisory From the American Heart Association.</h4><i>Lisanti AJ, Uzark KC, Harrison TM, Peterson JK, ... Jones CE, American Heart Association Pediatric Cardiovascular Nursing Committee of the Council on Cardiovascular and Stroke Nursing; Council on Lifelong Congenital Heart Disease and Heart Health in the Young; and Council on Hypertension</i><br /><AbstractText>Developmental disorders, disabilities, and delays are a common outcome for individuals with complex congenital heart disease, yet targeting early factors influencing these conditions after birth and during the neonatal hospitalization for cardiac surgery remains a critical need. The purpose of this science advisory is to (1) describe the burden of developmental disorders, disabilities, and delays for infants with complex congenital heart disease, (2) define the potential health and neurodevelopmental benefits of developmental care for infants with complex congenital heart disease, and (3) identify critical gaps in research aimed at evaluating developmental care interventions to improve neurodevelopmental outcomes in complex congenital heart disease. This call to action targets research scientists, clinicians, policymakers, government agencies, advocacy groups, and health care organization leadership to support funding and hospital-based infrastructure for developmental care in the complex congenital heart disease population. Prioritization of research on and implementation of developmental care interventions in this population should be a major focus in the next decade.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 17 Jan 2023:e7967; epub ahead of print</small></div>
Lisanti AJ, Uzark KC, Harrison TM, Peterson JK, ... Jones CE, American Heart Association Pediatric Cardiovascular Nursing Committee of the Council on Cardiovascular and Stroke Nursing; Council on Lifelong Congenital Heart Disease and Heart Health in the Young; and Council on Hypertension
J Am Heart Assoc: 17 Jan 2023:e7967; epub ahead of print | PMID: 36648070
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<div><h4>Congenital Heart Disease and Fertility: A Danish Nationwide Cohort Study Including Both Men and Women.</h4><i>Udholm LF, Arendt LH, Knudsen UB, Ramlau-Hansen CH, Hjortdal VE</i><br /><AbstractText><br /><b>Background:</b><br/>Despite an increasing number of patients with congenital heart disease (CHD) reaching reproductive age, the fertility of these patients remains undescribed. Therefore, the aim of the study was to evaluate the fertility in men and women with CHD by estimating the risk of infertility and comparing the birth rates, proportions of individuals becoming parents or remaining childless, and the number of children per parent with unaffected individuals. Methods and Results The study population consisted of individuals born between 1977 and 2000. Information on CHD, infertility, and live born children were obtained from the Danish health registries. Hazard ratios for infertility were analyzed using a Cox regression model. Differences of proportions and birth rates were calculated and compared between groups. Among 1 385 895 individuals, a total of 8679 (0.6%) were diagnosed with CHD. Men and women with simple or moderate CHD had no increased risk of infertility when compared with the reference population. Estimates for complex CHD groups were too imprecise for evaluation. Individuals with CHD were more often childless with consequently lower birth rates compared with unaffected individuals. However, those becoming parents had the same number of children as the reference population. <br /><b>Conclusions:</b><br/>Men and women with simple or moderate CHD had the same risk of infertility as the reference population. Despite patients with CHD more often being childless, those becoming parents had the same number of children as parents without CHD. The current findings increase the knowledge regarding fertility in the CHD population.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 17 Jan 2023; 12:e027409</small></div>
Udholm LF, Arendt LH, Knudsen UB, Ramlau-Hansen CH, Hjortdal VE
J Am Heart Assoc: 17 Jan 2023; 12:e027409 | PMID: 36648105
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<div><h4>Inflection Points in Blood Pressure Trajectories Preceding Hypertension Onset in Different Age Groups.</h4><i>Liu C, Zu C, Meng Q, Li R, ... Ye Z, Qin X</i><br /><AbstractText><br /><b>Background:</b><br/>Understanding the natural history of elevated blood pressure (BP) is important to determine the window for primary prevention of hypertension. The authors aimed to investigate the natural history of elevated BP and examine whether there were inflection points in BP trajectories preceding hypertension onset in Chinese adults. Methods and Results A total of 8688 participants with an average of 5 BP measurements were included from the CHNS (China Health and Nutrition Survey). In each wave, triplicate measurements on the same arm were taken, and the mean systolic BP (SBP) and diastolic BP (DBP) were used in the analysis. Hypertension onset was defined as SBP ≥140 mm Hg or DBP ≥90 mm Hg or diagnosed by physician or currently under antihypertensive treatment. The median follow-up time was 13.0 years. Overall, BP elevation with age prior to the onset of hypertension showed a nonlinear trajectory. The increased rates in both SBP and DBP were obviously faster after the inflection point than before. According to hypertension onset at age 30 to 39, 40 to 49, 50 to 59, 60 to 69, and 70 to 79 years, at the inflection point, patients were ≈29, 38, 48, 57, and 67 years, SBP levels were 112.6, 114.8, 116.8, 117.4, and 118.0 mm Hg, and DBP levels were 73.4, 75.7, 76.9, 76.2, and 73.8 mm Hg, respectively. <br /><b>Conclusions:</b><br/>There was a nonlinear trajectory of BP elevation preceding hypertension onset. The inflection points for SBP and DBP were in the range of 112 to 118 mm Hg and 73 to 77 mm Hg, respectively. Once BP levels exceeded the changing points, the level of SBP and DBP increased more rapidly.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 Jan 2023:e028472; epub ahead of print</small></div>
Liu C, Zu C, Meng Q, Li R, ... Ye Z, Qin X
J Am Heart Assoc: 16 Jan 2023:e028472; epub ahead of print | PMID: 36645073
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<div><h4>Large-Scale Metabolomics and the Incidence of Cardiovascular Disease.</h4><i>Lind L, Fall T, Ärnlöv J, Elmståhl S, Sundström J</i><br /><AbstractText><br /><b>Background:</b><br/>The study aimed to show the relationship between a large number of circulating metabolites and subsequent cardiovascular disease (CVD) and subclinical markers of CVD in the general population. Methods and Results In 2278 individuals free from CVD in the EpiHealth study (aged 45-75 years, mean age 61 years, 50% women), 790 annotated nonxenobiotic metabolites were measured by mass spectroscopy (Metabolon). The same metabolites were measured in the PIVUS (Prospective Investigation of Vasculature in Uppsala Seniors) study (n=603, all aged 80 years, 50% women), in which cardiac and carotid artery pathologies were evaluated by ultrasound. During a median follow-up of 8.6 years, 107 individuals experienced a CVD (fatal or nonfatal myocardial infarction, stroke, or heart failure) in EpiHealth. Using a false discovery rate of 0.05 for age- and sex-adjusted analyses and <i>P</i><0.05 for adjustment for traditional CVD risk factors, 37 metabolites were significantly related to incident CVD. These metabolites belonged to multiple biochemical classes, such as amino acids, lipids, and nucleotides. Top findings were dimethylglycine and N-acetylmethionine. A lasso selection of 5 metabolites improved discrimination when added on top of traditional CVD risk factors (+4.0%, <i>P</i>=0.0054). Thirty-five of the 37 metabolites were related to subclinical markers of CVD evaluated in the PIVUS study. The metabolite 1-carboxyethyltyrosine was associated with left atrial diameter as well as inversely related to both ejection fraction and the echogenicity of the carotid artery. <br /><b>Conclusions:</b><br/>Several metabolites were discovered to be associated with future CVD, as well as with subclinical markers of CVD. A selection of metabolites improved discrimination when added on top of CVD risk factors.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 Jan 2023:e026885; epub ahead of print</small></div>
Lind L, Fall T, Ärnlöv J, Elmståhl S, Sundström J
J Am Heart Assoc: 16 Jan 2023:e026885; epub ahead of print | PMID: 36645074
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<div><h4>Long-Term Outcomes and Duration of Dual Antiplatelet Therapy After Coronary Intervention With Second-Generation Drug-Eluting Stents: The Veterans Affairs Extended DAPT Study.</h4><i>Kinlay S, Young MM, Sherrod R, Gagnon DR</i><br /><AbstractText><br /><b>Background:</b><br/>Recent guidelines on dual antiplatelet therapy (DAPT) duration after percutaneous coronary intervention (PCI) balance the subsequent risks of major bleeding with ischemic events. Although generally favoring shorter DAPT duration with second-generation drug-eluting stents, the effects on long-term outcomes in the wider population are uncertain. Methods and Results We tracked all patients having PCI with second-generation drug-eluting stents in the Veterans Affairs Healthcare System between 2006 and 2016 for death, myocardial infarction, stroke, and major bleeding up to 13 years. We compared these outcomes with 4 DAPT durations of 1 to 5, 6 to 9, 10 to 12, and 13 to 18 months after the index PCI using hazard ratios (HRs) and 95% CIs from Cox proportional hazards models adjusted by inverse probability weighting. A total of 40 882 subjects with PCI were followed up for a median of 4.3 (25%-75%: 2.4-6.5) years. DAPT discontinuation was rare early after PCI (5.8% at 1-5 months and 6.3% at 6-9 months) but increased (19% and 44%) >9 months. The risk of cardiovascular and noncardiovascular death was higher (HR, 2.03-3.41) with DAPT discontinuation <9 months, likely reflecting premature cessation from factors related to early death. DAPT discontinuation after 9 months following PCI was associated with lower risks of death (HR, 0.93 [95% CI, 0.88-0.99]), cardiac death (HR, 0.79 [95% CI, 0.70-0.90]), myocardial infarction (HR, 0.75 [95% CI, 0.69-0.82]), and major bleeding (HR, 0.82 [95% CI, 0.74-0.91]). Results were similar with an index PCI for an acute coronary syndrome. <br /><b>Conclusions:</b><br/>Stopping DAPT after 9 months is associated with lower long-term risks of adverse ischemic and bleeding events and supports recent guidelines of shorter duration DAPT after PCI with second-generation drug-eluting stents.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 Jan 2023:e027055; epub ahead of print</small></div>
Kinlay S, Young MM, Sherrod R, Gagnon DR
J Am Heart Assoc: 16 Jan 2023:e027055; epub ahead of print | PMID: 36645075
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<div><h4>Heart-Brain Team Approach of Acute Myocardial Infarction Complicating Acute Stroke: Characteristics of Guideline-Recommended Coronary Revascularization and Antithrombotic Therapy and Cardiovascular and Bleeding Outcomes.</h4><i>Suzuki T, Kataoka Y, Shiozawa M, Morris K, ... Tsujita K, Noguchi T</i><br /><AbstractText><br /><b>Background:</b><br/>Acute myocardial infarction (AMI) infrequently occurs after acute stroke. The Heart-brain team approach has a potential to appropriately manage this poststroke cardiovascular complication. However, clinical outcomes of AMI complicating acute stroke (AMI-CAS) with the heart-brain team approach have not been characterized. The current study investigated cardiovascular outcomes in patients with AMI-CAS managed by a heart-brain team. Methods and Results We retrospectively analyzed 2390 patients with AMI at our institute (January 1, 2007-September 30, 2020). AMI-CAS was defined as the occurrence of AMI within 14 days after acute stroke. Major adverse cerebral/cardiovascular events (cardiac-cause death, nonfatal myocardial infarction, and nonfatal stroke) and major bleeding events were compared in subjects with  AMI-CAS and those without acute stroke. AMI-CAS was identified in 1.6% of the subjects. Most AMI-CASs (37/39=94.9%) presented ischemic stroke. Median duration of AMI from the onset of acute stroke was 2 days. Patients with AMI-CAS less frequently received primary percutaneous coronary intervention (43.6% versus 84.7%; <i>P</i><0.001) and dual-antiplatelet therapy (38.5% versus 85.7%; <i>P</i><0.001), and 33.3% of them did not receive any antithrombotic agents (versus 1.3%; <i>P</i><0.001). During the observational period (median, 2.4 years [interquartile range, 1.1-4.4 years]), patients with AMI-CAS exhibited a greater likelihood of experiencing major adverse cerebral/cardiovascular events (hazard ratio [HR], 3.47 [95% CI, 1.99-6.05]; <i>P</i><0.001) and major bleeding events (HR, 3.30 [95% CI, 1.34-8.10]; <i>P</i>=0.009). These relationships still existed even after adjusting for clinical characteristics and medication use (major adverse cerebral/cardiovascular event: HR, 1.87 [95% CI, 1.02-3.42]; <i>P</i>=0.04; major bleeding: HR, 2.67 [95% CI, 1.03-6.93]; <i>P</i>=0.04). <br /><b>Conclusions:</b><br/>Under the heart-brain team approach, AMI-CAS was still a challenging disease, reflected by less adoption of primary percutaneous coronary intervention and antithrombotic therapies, with substantially elevated cardiovascular and major bleeding risks. Our findings underscore the need for a further refined approach to mitigate their ischemic/bleeding risks.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 Jan 2023:e8140; epub ahead of print</small></div>
Suzuki T, Kataoka Y, Shiozawa M, Morris K, ... Tsujita K, Noguchi T
J Am Heart Assoc: 16 Jan 2023:e8140; epub ahead of print | PMID: 36645078
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<div><h4>Impaired Elastic Properties of the Ascending Aorta in Fetuses With Coarctation of the Aorta.</h4><i>Xu R, Zhou D, Liu Y, Yao L, ... Zhou Q, Zeng S</i><br /><AbstractText><br /><b>Background:</b><br/>Abnormal aortic elastic properties are major notable vasculopathy involved in coarctation of the aorta (CoA). However, there are no reports on aortic wall elastic characteristics in fetuses with CoA. Methods and Results Fifty-six fetuses with CoA and 56 normal controls were included in this prospective case-control study. The dimensions of the cardiac chamber, the size of the aorta, left ventricular myocardial performance indexes, and aortic elastic properties, including the global circumferential strain, fractional area change and mean longitudinal strain, were measured serially in utero. The global circumferential strain, fractional area change, and mean longitudinal strain in fetuses with CoA were smaller than those in the normal group at both the first and last examinations (18.50% versus 37.73% for global circumferential strain, 38.90% versus 57.55% for fractional area change, 6.61% versus 11.81% for mean longitudinal strain at first scan, 16.62% versus 42.05% for global circumferential strain, 36.54% versus 59.7% for fractional area change, 6.2% versus 11.46% for mean longitudinal strain at last scan, all <i>P</i><0.001). There were negative correlations between aortic elastic properties and left ventricular myocardial performance indexes in fetuses with CoA (<i>P</i><0.01). Aortic elastic properties were correlated positively with aortic isthmus size in fetuses with CoA (<i>P</i><0.01). <br /><b>Conclusions:</b><br/>Aortic strain and the fractional area change were decreased in fetuses with CoA. Impairments of these aortic elastic properties were associated with diminished heart function and aortic isthmus size in utero. Further large-scale longitudinal studies are required to confirm the potential predictive value of cardiovascular morbidity (ie, hypertension) in fetuses with CoA.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 Jan 2023:e028015; epub ahead of print</small></div>
Xu R, Zhou D, Liu Y, Yao L, ... Zhou Q, Zeng S
J Am Heart Assoc: 16 Jan 2023:e028015; epub ahead of print | PMID: 36645085
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<div><h4>Scavenger Receptors in Myocardial Infarction and Ischemia/Reperfusion Injury: The Potential for Disease Evaluation and Therapy.</h4><i>Zhang J, Ding W, Liu J, Wan J, Wang M</i><br /><AbstractText>Scavenger receptors (SRs) are a structurally heterogeneous superfamily of evolutionarily conserved receptors that are divided into classes A to J. SRs can recognize multiple ligands, such as modified lipoproteins, damage-associated molecular patterns, and pathogen-associated molecular patterns, and regulate lipid metabolism, immunity, and homeostasis. According to the literature, SRs may play a critical role in myocardial infarction and ischemia/reperfusion injury, and the soluble types of SRs may be a series of promising biomarkers for the diagnosis and prognosis of patients with acute coronary syndrome or acute myocardial infarction. In this review, we briefly summarize the structure and function of SRs and discuss the association between each SR and ischemic cardiac injury in patients and animal models in detail. A better understanding of the effect of SRs on ischemic cardiac injury will inspire novel ideas for therapeutic drug discovery and disease evaluation in patients with myocardial infarction.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 Jan 2023:e027862; epub ahead of print</small></div>
Zhang J, Ding W, Liu J, Wan J, Wang M
J Am Heart Assoc: 16 Jan 2023:e027862; epub ahead of print | PMID: 36645089
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<div><h4>Reverse Atrial Remodeling in Heart Failure With Recovered Ejection Fraction.</h4><i>Sun Y, Chen X, Zhang Y, Yu Y, ... Tse G, Liu Y</i><br /><AbstractText><br /><b>Background:</b><br/>Heart failure with recovered ejection fraction (HFrecEF) has been a newly recognized entity since 2020. However, the concept has primarily focused on left ventricular ejection fraction improvement, with less focus on the recovery of the left atrium. In this study, we investigated changes in left atrial (LA) echocardiographic indices in HFrecEF. Methods and Results An inpatient cohort with heart failure with reduced ejection fraction (HFrEF) was identified retrospectively and followed up prospectively in a single tertiary hospital. The enrolled patients were classified into HFrecEF and persistent HFrEF groups. Alternations in LA parameters by echocardiography were calculated. The primary outcome was a composite of cardiovascular death or heart failure rehospitalization. A total of 699 patients were included (HFrecEF: n=228; persistent HFrEF: n=471). Compared with persistent HFrEF, the HFrecEF group had greater reductions in LA diameter, LA transverse diameter, LA superior-inferior diameter, LA volume, and LA volume index but not in LA sphericity index. Cox regression analysis showed that the HFrecEF group experienced lower risks of prespecified end points than the persistent HFrEF group after adjusting for confounders. Additionally, 136 (59.6%) and 62 (13.0%) patients showed LA reverse remodeling (LARR) for the HFrecEF and persistent HFrEF groups, respectively. Among the HFrecEF subgroup, patients with LARR had better prognosis compared with those without LARR. Multivariate logistic analysis demonstrated that age and coronary heart disease were 2 independent negative predictors for LARR. <br /><b>Conclusions:</b><br/>In HFrecEF, both left ventricular systolic function and LA structure remodeling were improved. Patients with HFrecEF with LARR had improved clinical outcomes, indicating that the evaluation of LA size provides a useful biomarker for risk stratification of heart failure.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 Jan 2023:e8124; epub ahead of print</small></div>
Sun Y, Chen X, Zhang Y, Yu Y, ... Tse G, Liu Y
J Am Heart Assoc: 16 Jan 2023:e8124; epub ahead of print | PMID: 36645090
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<div><h4>Circulating Progenitor Cells Are Associated With Bioprosthetic Aortic Valve Deterioration: A Preliminary Study.</h4><i>Kanaji Y, Ozcan I, Toya T, Gulati R, ... Lerman LO, Lerman A</i><br /><AbstractText><br /><b>Background:</b><br/>Mechanisms underlying bioprosthetic valve deterioration are multifactorial and incompletely elucidated. Reparative circulating progenitor cells, and conversely calcification-associated osteocalcin expressing circulating progenitor cells, have been linked to native aortic valve deterioration. However, their role in bioprosthetic valve deterioration remains elusive. This study sought to evaluate the contribution of different subpopulations of circulating progenitor cells in bioprosthetic valve deterioration. Methods and Results This single-center prospective study enrolled 121 patients who had peripheral blood mononuclear cells isolated before bioprosthetic aortic valve replacement and had an echocardiographic follow-up ≥2 years after the procedure. Using flow cytometry, fresh peripheral blood mononuclear cells were analyzed for the surface markers CD34, CD133, and osteocalcin. Bioprosthetic valve deterioration was evaluated by hemodynamic valve deterioration (HVD) using echocardiography, which was defined as an elevated mean transprosthetic gradient ≥30 mm Hg or at least moderate intraprosthetic regurgitation. Sixteen patients (13.2%) developed HVD during follow-up for a median of 5.9 years. Patients with HVD showed significantly lower levels of reparative CD34<sup>+</sup>CD133<sup>+</sup> cells and higher levels of osteocalcin-positive cells than those without HVD (CD34<sup>+</sup>CD133<sup>+</sup> cells: 125 [80, 210] versus 270 [130, 420], <i>P</i>=0.002; osteocalcin-positive cells: 3060 [523, 5528] versus 670 [180, 1930], <i>P</i>=0.005 respectively). Decreased level of CD34<sup>+</sup>CD133<sup>+</sup> cells was a significant predictor of HVD (hazard ratio, 0.995 [95% CI, 0.990%-0.999%]). <br /><b>Conclusions:</b><br/>Circulating levels of CD34<sup>+</sup>CD133<sup>+</sup> cells and osteocalcin-positive cells were significantly associated with the subsequent occurrence of HVD in patients undergoing bioprosthetic aortic valve replacement. Circulating progenitor cells might play a vital role in the mechanism, risk stratification, and a potential therapeutic target for patients with bioprosthetic valve deterioration.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 Jan 2023:e027364; epub ahead of print</small></div>
Kanaji Y, Ozcan I, Toya T, Gulati R, ... Lerman LO, Lerman A
J Am Heart Assoc: 16 Jan 2023:e027364; epub ahead of print | PMID: 36645093
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<div><h4>Elevated Uric Acid Is Associated With New-Onset Atrial Fibrillation: Results From the Swedish AMORIS Cohort.</h4><i>Ding M, Viet NN, Gigante B, Lind V, Hammar N, Modig K</i><br /><AbstractText><br /><b>Background:</b><br/>The role of uric acid is gaining increasing importance in the evaluation of cardiovascular disease, but its relationship with atrial fibrillation (AF) is unclear. This study aims to investigate the association between uric acid levels and risk of new-onset AF. Methods and Results A total of 339 604 individuals 30 to 60 years of age and free from cardiovascular disease at baseline (1985-1996) in the Swedish AMORIS (Apolipoprotein-Mortality Risk) cohort were followed until December 31, 2019 for incident AF. Cox regression models were used to examine the association between uric acid and AF, adjusting for potential confounders and stratifying by incident cardiovascular disease. Over a mean follow-up of 25.9 years, 46 516 incident AF cases occurred. Compared with the lowest uric acid quartile, each of the upper 3 quartiles were associated with an increased risk of AF in a dose-response manner. Adjusted hazard ratios were 1.09 (95% CI, 1.06-1.12) for second quartile, 1.19 (95% CI, 1.16-1.23) for third quartile, and 1.45 (95% CI, 1.41-1.49) for fourth quartile. The association was similar among individuals with and without incident hypertension, diabetes, heart failure, or coronary heart disease. The dose-response pattern was further supported in a subsample of individuals with repeated measurements of uric acid. <br /><b>Conclusions:</b><br/>Elevated uric acid was associated with an increased risk of AF, not only among people with cardiovascular disease and cardiovascular risk factors but also among those without. Future investigations are needed to examine whether lowering uric acid is relevant for AF prevention.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 12 Jan 2023:e027089; epub ahead of print</small></div>
Ding M, Viet NN, Gigante B, Lind V, Hammar N, Modig K
J Am Heart Assoc: 12 Jan 2023:e027089; epub ahead of print | PMID: 36633024
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<div><h4>High Prevalence of Geriatric Conditions Among Older Adults With Cardiovascular Disease.</h4><i>Aïdoud A, Gana W, Poitau F, Debacq C, ... Angoulvant D, Fougère B</i><br /><AbstractText>As the population ages, the global cardiovascular disease burden will continue to increase, particularly among older adults. Increases in life expectancy and better cardiovascular care have significantly reshaped the epidemiology of cardiovascular disease and have created new patient profiles. The combination of older age, multiple comorbidities, polypharmacy, frailty, and adverse noncardiovascular outcomes is challenging our routine clinical practice in this field. In this review, we examine noncardiovascular factors that statistically interact in a relevant way with health status and quality of life in older people with cardiovascular disease. We focused on specific geriatric conditions (multimorbidity, polypharmacy, geriatric syndromes, and frailty) that are responsible for a major risk of functional decline and have an important impact on the overall prognosis in this patient population.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 11 Jan 2023:e026850; epub ahead of print</small></div>
Aïdoud A, Gana W, Poitau F, Debacq C, ... Angoulvant D, Fougère B
J Am Heart Assoc: 11 Jan 2023:e026850; epub ahead of print | PMID: 36628962
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<div><h4>Aortic Valve Reconstruction With Autologous Pericardium Versus a Bioprosthesis: The Ozaki Procedure in Perspective.</h4><i>Unai S, Ozaki S, Johnston DR, Saito T, ... Blackstone EH, Pettersson GB</i><br /><AbstractText><br /><b>Background:</b><br/>We assessed the Ozaki procedure, aortic valve reconstruction using autologous pericardium, with respect to its learning curve, hemodynamic performance, and durability compared with a stented bioprosthesis. Methods and Results From January 2007 to January 2016, 776 patients underwent an Ozaki procedure at Toho University Ohashi Medical Center. Learning curves, aortic regurgitation (AR), and peak gradient, assessed by serial echocardiograms, valve rereplacement, and survival were investigated. Valve performance and durability were compared with 627 1:1 propensity-matched patients receiving stented bovine pericardial valves implanted from 1982 to 2011 at Cleveland Clinic. Learning curves were observed for aortic clamp and cardiopulmonary bypass times, AR prevalence, and early mortality. Decreased aortic clamp time was observed over the first 300 cases. New surgeons performing parts of the procedure after case 400 resulted in a slight increase in aortic clamp and cardiopulmonary bypass times. Among matched patients, the Ozaki cohort had more AR than the PERIMOUNT cohort (severe AR at 1 and 6 years, 0.58% and 3.6% versus 0.45% and 1.0%, respectively; <i>P</i>[trend]=0.006), although with a steep learning curve. Peak gradient showed the opposite trend: 14 and 17 mm Hg for Ozaki and 24 and 28 mm Hg for PERIMOUNT at these times (<i>P</i>[trend]<i><</i>0.001). Freedom from rereplacement was similar (<i>P</i>=0.491). Survival of the Ozaki cohort was 85% at 6 years. <br /><b>Conclusions:</b><br/>Patients undergoing the Ozaki procedure had lower gradients but more recurrent AR than those receiving PERIMOUNT bioprostheses. Although recurrent AR is concerning, results confirm low risk and good midterm performance of the Ozaki procedure, supporting its continued use.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 11 Jan 2023:e027391; epub ahead of print</small></div>
Unai S, Ozaki S, Johnston DR, Saito T, ... Blackstone EH, Pettersson GB
J Am Heart Assoc: 11 Jan 2023:e027391; epub ahead of print | PMID: 36628965
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<div><h4>Adolescent Psychological Assets and Cardiometabolic Health Maintenance in Adulthood: Implications for Health Equity.</h4><i>Qureshi F, Guimond AJ, Tsao E, Delaney S, Boehm JK, Kubzansky LD</i><br /><AbstractText><br /><b>Background:</b><br/>Positive cardiometabolic health (CMH) is defined as meeting recommended levels of multiple cardiometabolic risk factors in the absence of manifest disease. Prior work finds that few individuals-particularly members of minoritized racial and ethnic groups-meet these criteria. This study investigated whether psychological assets help adolescents sustain CMH in adulthood and explored interactions by race and ethnicity. Methods and Results Participants were 3478 individuals in the National Longitudinal Study of Adolescent Health (49% female; 67% White, 15% Black, 11% Latinx, 6% other [Native American, Asian, or not specified]). In Wave 1 (1994-1995; mean age=16 years), data on 5 psychological assets (optimism, happiness, self-esteem, belongingness, and feeling loved) were used to create a composite asset index (range=0-5). In Waves 4 (2008; mean age=28 years) and 5 (2016-2018; mean age=38 years), CMH was defined using 7 clinically assessed biomarkers. Participants with healthy levels of ≥6 biomarkers at Waves 4 and 5 were classified as maintaining CMH over time. The prevalence of CMH maintenance was 12%. Having more psychological assets was associated with better health in adulthood (odds ratio [OR]<sub>linear trend</sub>, 1.12 [95% CI, 1.01-1.25]). Subgroup analyses found substantive associations only among Black participants (OR, 1.35 [95% CI, 1.00-1.82]). Additionally, there was some evidence that racial and ethnic disparities in CMH maintenance may be less pronounced among participants with more assets. <br /><b>Conclusions:</b><br/>Youth with more psychological assets were more likely to experience favorable CMH patterns 2 decades later. The strongest associations were observed among Black individuals. Fostering psychological assets in adolescence may help prevent cardiovascular disease and play an underappreciated role in shaping health inequities.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 11 Jan 2023:e026173; epub ahead of print</small></div>
Qureshi F, Guimond AJ, Tsao E, Delaney S, Boehm JK, Kubzansky LD
J Am Heart Assoc: 11 Jan 2023:e026173; epub ahead of print | PMID: 36628968
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<div><h4>Age-Dependent Association Between Modifiable Risk Factors and Incident Cardiovascular Disease.</h4><i>Kaneko H, Yano Y, Okada A, Itoh H, ... Yasunaga H, Komuro I</i><br /><AbstractText><br /><b>Background:</b><br/>There have been limited data examining the age-dependent relationship of wide-range risk factors with the incidence of each subtype of cardiovascular disease (CVD) event. We assessed age-related associations between modifiable risk factors and the incidence of CVD. Methods and Results We analyzed 3 027 839 participants without a CVD history enrolled in the JMDC Claims Database (mean age, 44.8±11.0 years; 57.6% men). Each participant was categorized as aged 20 to 49 years (n=2 008 559), 50 to 59 years (n=712 273), and 60 to 75 years (n=307 007). Using Cox proportional hazards models and the relative risk reduction, we identified associations between risk factors and incident CVD, consisting of myocardial infarction, angina pectoris, stroke, and heart failure (HF). We assessed whether the association of risk factors for developing CVD would be modified by age category. Over a mean follow-up of 1133 days, 6315 myocardial infarction, 56 447 angina pectoris, 28 079 stroke, and 56 369 HF events were recorded. The incidence of myocardial infarction, angina pectoris, stroke, and HF increased with age category. Hazard ratios of obesity, hypertension, and diabetes in the multivariable Cox regression analyses for myocardial infarction, angina pectoris, stroke, and HF decreased with age category. The relative risk reduction of obesity, hypertension, and diabetes for CVD events decreased with age category. For example, the relative risk reduction of hypertension for HF decreased from 59.2% in participants aged 20 to 49 years to 38.1% in those aged 60 to 75 years. <br /><b>Conclusions:</b><br/>The contribution of modifiable risk factor to the development of CVD is greater in younger compared with older individuals. Preventive efforts for risk factor modification may be more effective in younger people.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 11 Jan 2023:e027684; epub ahead of print</small></div>
Kaneko H, Yano Y, Okada A, Itoh H, ... Yasunaga H, Komuro I
J Am Heart Assoc: 11 Jan 2023:e027684; epub ahead of print | PMID: 36628975
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<div><h4>Evidence of Carotid Atherosclerosis Vulnerability Regression in Real Life From Magnetic Resonance Imaging: Results of the MAGNETIC Prospective Study.</h4><i>Catalano O, Bendotti G, Aloi TL, Bardile AF, ... Forni G, La Rovere MT</i><br /><AbstractText><br /><b>Background:</b><br/>Atherosclerosis vulnerability regression has been evidenced mostly in randomized clinical trials with intensive lipid-lowering therapy. We aimed to demonstrate vulnerability regression in real life, with a comprehensive quantitative method, in patients with asymptomatic mild to moderate carotid atherosclerosis on a secondary prevention program. Methods and Results We conducted a single-center prospective observational study (MAGNETIC [Magnetic Resonance Imaging as a Gold Standard for Noninvasive Evaluation of Atherosclerotic Involvement of Carotid Arteries]): 260 patients enrolled at a cardiac rehabilitation center were followed for 3 years with serial magnetic resonance imaging. Per section cutoffs (95th/5th percentiles) were derived from a sample of 20 consecutive magnetic resonance imaging scans: (1) lipid-rich necrotic core: 26% of vessel wall area; (2) intraplaque hemorrhage: 12% of vessel wall area; and (3) fibrous cap: (a) minimum thickness: 0.06 mm, (b) mean thickness: 0.4 mm, (c) projection length: 11 mm. Patients with baseline magnetic resonance imaging of adequate quality (n=247) were classified as high (n=63, 26%), intermediate (n=65, 26%), or low risk (n=119, 48%), if vulnerability criteria were fulfilled in ≥2 contiguous sections, in 1 or multiple noncontiguous sections, or in any section, respectively. Among high-risk patients, a conversion to any lower-risk status was found in 11 (17%; <i>P</i>=0.614) at 6 months, in 16 (25%; <i>P</i>=0.197) at 1 year, and in 19 (30%; <i>P</i>=0.009) at 3 years. Among patients showing any degree of carotid plaque vulnerability, 21 (16%; <i>P</i>=0.014) were diagnosed at low risk at 3 years. <br /><b>Conclusions:</b><br/>This study demonstrates with a quantitative approach that vulnerability regression is common in real life. A secondary prevention program can promote vulnerability regression in asymptomatic patients in the mid to long term.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 11 Jan 2023:e026469; epub ahead of print</small></div>
Catalano O, Bendotti G, Aloi TL, Bardile AF, ... Forni G, La Rovere MT
J Am Heart Assoc: 11 Jan 2023:e026469; epub ahead of print | PMID: 36628977
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<div><h4>Gaps in the Care of Pulmonary Hypertension: A Cross-Sectional Patient Simulation Study Among Practicing Cardiologists and Pulmonologists.</h4><i>de Belen E, McConnell JW, Elwing JM, Paculdo D, ... Linder J, Peabody JW</i><br /><AbstractText><br /><b>Background:</b><br/>Diagnosis of pulmonary hypertension (PH) is often delayed or missed, leading to disease progression and missed treatment opportunities. In this study, we measured variation in care provided by board-certified cardiologists and pulmonologists in simulated patients with potentially undiagnosed PH. Methods and Results In a cross-sectional study (https://www.clinicaltrials.gov, NCT04693793), 219 US practicing cardiologists and pulmonologists cared for simulated patients presenting with symptoms of chronic dyspnea and associated signs of potential PH. We scored the clinical quality-of-care decisions made in a clinical encounter against predetermined evidence-based criteria. Overall, quality-of-care scores ranged from 18% to 74%, averaging 43.2%±11.5%. PH, when present, was correctly suspected 49.1% of the time. Conversely, physicians incorrectly identified PH in 53.7% of non-PH cases. Physicians ordered 2-dimensional echocardiography in just 64.3% of cases overall. Physicians who ordered 2-dimensional echocardiography in the PH cases were significantly more likely to get the presumptive diagnosis (61.9% versus 30.7%; <i>P</i><0.001). Ordering other diagnostic work-up items showed similar results for ventilation/perfusion scan (81.5% versus 51.4%; <i>P</i>=0.005) and high-resolution computed tomography (60.4% versus 43.2%; <i>P</i>=0.001). Physicians who correctly identified PH were significantly more likely to order confirmatory right heart catheterization or refer to PH center (67.3% versus 15.8%; <i>P</i><0.001). <br /><b>Conclusions:</b><br/>A wide range of care in the clinical practice among simulated patients presenting with possible PH was found, specifically in the evaluation and plan for definitive diagnosis of patients with PH. The delay or misdiagnosis of PH is likely attributed to a low clinical suspicion, nonspecific symptoms, and underuse of key diagnostic tests. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04693793.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 11 Jan 2023:e026413; epub ahead of print</small></div>
de Belen E, McConnell JW, Elwing JM, Paculdo D, ... Linder J, Peabody JW
J Am Heart Assoc: 11 Jan 2023:e026413; epub ahead of print | PMID: 36628980
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<div><h4>In-Hospital ECG Findings, Changes in Medical Management, and Cardiovascular Outcomes in Patients With Acute Stroke or Transient Ischemic Attack.</h4><i>Olma MC, Tütüncü S, Fiessler C, Kunze C, ... Endres M, MonDAFIS Investigators [Link]</i><br /><AbstractText><br /><b>Background:</b><br/>In patients with acute ischemic stroke, little is known regarding the frequency of abnormal ECG findings other than atrial fibrillation and their association with cardiovascular outcomes. We aim to analyze the frequency and type of abnormal ECG findings, subsequent changes in medical treatment, and their association with cardiovascular outcomes in patients with acute ischemic stroke. Methods and Results In the investigator-initiated multicenter MonDAFIS (impact of standardized monitoring for detection of atrial fibrillation in ischemic stroke) study, 3465 patients with acute ischemic stroke or transient ischemic attack and without known atrial fibrillation were randomized 1:1 to receive Holter-ECG for up to 7 days in-hospital with systematic evaluation in a core cardiology laboratory (intervention group) or standard diagnostic care (control group). Outcomes included predefined abnormal ECG findings (eg, pauses, atrial fibrillation, brady-/tachycardias), medical management in the intervention group, and combined vascular end point (recurrent stroke, myocardial infarction, major bleeds, or all-cause death) and mortality at 24 months in both randomization groups. Predefined abnormal ECG findings were detected in 326 of 1693 (19.3%) patients in the intervention group. Twenty of these 326 patients (6.1%) received a pacemaker, and 62 of 326 (19.0%) patients had newly initiated or discontinued β-blocker medication. Discontinuation of β-blockers was associated with a higher death rate in the control group than in the intervention group during 24 months after enrollment (adjusted hazard ratio, 11.0 [95% CI, 2.4-50.4]; <i>P</i>=0.025 for interaction). <br /><b>Conclusions:</b><br/>Systematic in-hospital Holter ECG reveals abnormal findings in 1 of 5 patients with acute stroke, and mortality was lower at 24 months in patients with systematic ECG recording in the hospital. Further studies are needed to determine the potential impact of medical management of abnormal ECG findings. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02204267.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 11 Jan 2023:e027149; epub ahead of print</small></div>
Olma MC, Tütüncü S, Fiessler C, Kunze C, ... Endres M, MonDAFIS Investigators [Link]
J Am Heart Assoc: 11 Jan 2023:e027149; epub ahead of print | PMID: 36628982
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<div><h4>Effects of the Dietary Approaches to Stop Hypertension Diet on Change in Cardiac Biomarkers Over Time: Results From the DASH-Sodium Trial.</h4><i>Belanger MJ, Kovell LC, Turkson-Ocran RA, Mukamal KJ, ... Chang AR, Juraschek SP</i><br /><AbstractText><br /><b>Background:</b><br/>The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to reduce biomarkers of cardiovascular disease. We aimed to characterize the time course of change in biomarkers of cardiac injury (high-sensitivity cardiac troponin I), cardiac strain (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and inflammation (hs-CRP [high-sensitivity C-reactive protein]) while consuming the DASH diet. Methods and Results The DASH-Sodium trial was a randomized controlled trial of 412 adults with elevated blood pressure or hypertension. Participants were randomly assigned to 12 weeks of the DASH diet or a typical American diet. Energy intake was adjusted to maintain body weight. Measurements of high-sensitivity cardiac troponin I, NT-proBNP, and hs-CRP were performed in stored serum specimens, collected at baseline and ≈4, 8, and 12 weeks after randomization. In both the control diet and DASH diet, levels of NT-proBNP decreased; however, there was no difference between diets (<i>P</i>-trend compared with control=0.22). On the DASH diet versus control, levels of high-sensitivity cardiac troponin I decreased progressively during follow-up (<i>P-</i>trend compared with control=0.025), but a statistically significant between-diet difference in change from baseline levels was not observed until week 12 (% difference, 17.78% [95% CI, -29.51% to -4.09%]). A similar pattern was evident for hs-CRP (<i>P-</i>trend compared with control=0.01; % difference at week 12, 19.97% [95% CI, -31.94% to -5.89%]). <br /><b>Conclusions:</b><br/>In comparison with a typical American diet, the DASH diet reduced high-sensitivity cardiac troponin I and hs-CRP progressively over 12 weeks. These results suggest that the DASH diet has cumulative benefits over time on biomarkers of subclinical cardiac injury and inflammation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00000608.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 11 Jan 2023:e026684; epub ahead of print</small></div>
Belanger MJ, Kovell LC, Turkson-Ocran RA, Mukamal KJ, ... Chang AR, Juraschek SP
J Am Heart Assoc: 11 Jan 2023:e026684; epub ahead of print | PMID: 36628985
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<div><h4>Social Determinants of Cardiovascular Health: A Longitudinal Analysis of Cardiovascular Disease Mortality in US Counties From 2009 to 2018.</h4><i>Son H, Zhang D, Shen Y, Jaysing A, ... Li Y, Pagán JA</i><br /><AbstractText><br /><b>Background:</b><br/>Disparities in cardiovascular disease (CVD) outcomes persist across the United States. Social determinants of health play an important role in driving these disparities. The current study aims to identify the most important social determinants associated with CVD mortality over time in US counties. Methods and Results The authors used the Agency for Healthcare Research and Quality\'s database on social determinants of health and linked it with CVD mortality data at the county level from 2009 to 2018. The age-standardized CVD mortality rate was measured as the number of deaths per 100 000 people. Penalized generalized estimating equations were used to select social determinants associated with county-level CVD mortality. The analytic sample included 3142 counties. The penalized generalized estimating equation identified 17 key social determinants of health including rural-urban status, county\'s racial composition, income, food, and housing status. Over the 10-year period, CVD mortality declined at an annual rate of 1.08 (95% CI, 0.74-1.42) deaths per 100 000 people. Rural counties and counties with a higher percentage of Black residents had a consistently higher CVD mortality rate than urban counties and counties with a lower percentage of Black residents. The rural-urban CVD mortality gap did not change significantly over the past decade, whereas the association between the percentage of Black residents and CVD mortality showed a significant diminishing trend over time. <br /><b>Conclusions:</b><br/>County-level CVD mortality declined from 2009 through 2018. However, rural counties and counties with a higher percentage of Black residents continued to experience higher CVD mortality. Median income, food, and housing status consistently predicted higher CVD mortality.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 10 Jan 2023:e026940; epub ahead of print</small></div>
Son H, Zhang D, Shen Y, Jaysing A, ... Li Y, Pagán JA
J Am Heart Assoc: 10 Jan 2023:e026940; epub ahead of print | PMID: 36625296
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<div><h4>Independent Relevance of Different Measures of Adiposity for Carotid Intima-Media Thickness in 40 000 Adults in UK Biobank.</h4><i>Pillay P, Carter J, Taylor H, Lewington S, Clarke R</i><br /><AbstractText><br /><b>Background:</b><br/>Uncertainty persists about carotid intima-media thickness (CIMT) as a marker of subclinical atherosclerosis and the independent relevance of different measures of adiposity for CIMT. We assessed the independent relevance of general adiposity (body mass index), central adiposity (waist circumference), and body composition (fat mass index and fat-free mass index) with CIMT among adults in the United Kingdom. Methods and Results Multivariable linear regression of cross-sectional analyses of UK Biobank assessed the mean percentage difference in CIMT associated with equivalent differences in adiposity measures. To assess independent associations, body mass index and waist circumference were mutually adjusted, as were fat mass index and fat-free mass index. Among 39 367 participants (mean [SD] age 64 [8] years, 52% female, 97% White), median (interquartile range) CIMT was 0.65 (0.14) mm in women and 0.69 (0.18) mm in men. All adiposity measures were linearly and positively associated with CIMT after adjusting for confounders. Fat-free mass index was most strongly associated with CIMT after adjustment for fat mass index (% difference in CIMT: 1.23 [95% CI 0.93-1.53] women; 3.44 [3.01-3.86] men), while associations of fat mass index were attenuated after adjustment for fat-free mass index (0.28 [-0.02, 0.58] women; -0.59 [-0.99, -0.18] men). After mutual adjustment, body mass index remained positively associated with CIMT, but waist circumference was completely attenuated. <br /><b>Conclusions:</b><br/>Fat-free mass index was the adiposity measure most strongly associated with CIMT, suggesting that CIMT may reflect vascular compensatory remodeling rather than atherosclerosis. Hence, screening for subclinical atherosclerosis should evaluate carotid plaques in addition to CIMT.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 10 Jan 2023:e8051; epub ahead of print</small></div>
Pillay P, Carter J, Taylor H, Lewington S, Clarke R
J Am Heart Assoc: 10 Jan 2023:e8051; epub ahead of print | PMID: 36625300
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<div><h4>US Trends in Cholesterol Screening, Lipid Levels, and Lipid-Lowering Medication Use in US Adults, 1999 to 2018.</h4><i>Gao Y, Shah LM, Ding J, Martin SS</i><br /><AbstractText><br /><b>Background:</b><br/>Understanding current trends in cholesterol screening, lipid levels, and lipid management therapies may inform health policy and practice. Methods and Results In 50 928 US adult National Health and Nutrition Examination Survey (NHANES) participants, trends were assessed in cholesterol screening, mean levels of total cholesterol, triglycerides, low-density-lipoprotein cholesterol, and lipid-lowering medication use from 1999 through 2018. Point estimates were also calculated using the 2017 to March 2020 prepandemic data set. The age- and sex-adjusted proportion of having cholesterol screened within 5 years increased from 63.2% (95% CI, 60.0-66.3) in 1999 to 2000 to 72.5% (95% CI, 69.5-75.3) in 2017 to 2018 (<i>P</i><0.001 for linear trend). Mean total cholesterol decreased from 203.3 mg/dL (95% CI, 201.0-205.7) in 1999 to 2000 to 188.4 mg/dL in 2017 to 2018 (95% CI, 185.4-191.5) (<i>P</i><0.001 for nonlinear trend). The mean triglyceride level decreased from 121.3 mg/dL (95% CI, 116.4-126.4) in 1999 to 2000 to 91.4 mg/dL (95% CI, 88.4-94.6) in 2017 to 2018 (<i>P</i><0.001 for nonlinear trend). Low-density lipoprotein cholesterol decreased from 127.9 mg/dL (95% CI, 125.3-130.5) in 1999 to 2000 to 111.7 mg/dL (95% CI, 109.0-114.4) in 2017 to 2018 (<i>P</i><0.001 for nonlinear trend). Among statin-eligible US adults, the proportion of statin use increased from 14.9% (95% CI, 12.2-17.9) in 1999 to 2000 to 27.8% (95% CI, 23.0-33.2) in 2017 to 2018 (<i>P</i><0.001 for nonlinear trend). Statin use increased in adults with diabetes aged 40 to 75 years from 21.4% in 1999 to 2000 to 51.9% in 2017 to 2018 (<i>P</i><0.001 for overall linear trend). Statin use plateaued in all other groups. The proportions of using ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors were 3.7% (95% CI, 1.3-9.8) and 0.03% (95% CI, 0.01-0.15) in 2017 to March 2020, respectively. <br /><b>Conclusions:</b><br/>From 1999 through 2018, cholesterol screening increased while mean total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels decreased, with a modest increase in statin use and low uptake of nonstatin therapy in the US population.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 10 Jan 2023:e028205; epub ahead of print</small></div>
Gao Y, Shah LM, Ding J, Martin SS
J Am Heart Assoc: 10 Jan 2023:e028205; epub ahead of print | PMID: 36625302
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<div><h4>Prescribing Trends of Oral Anticoagulants in US Patients With Cirrhosis and Nonvalvular Atrial Fibrillation.</h4><i>Simon TG, Schneeweiss S, Singer DE, Sreedhara SK, Lin KJ</i><br /><AbstractText><br /><b>Background:</b><br/>Many patients with cirrhosis have concurrent nonvalvular atrial fibrillation (NVAF). Data are lacking regarding recent oral anticoagulant (OAC) usage trends among US patients with cirrhosis and NVAF. Methods and Results Using MarketScan claims data (2012-2019), we identified patients with cirrhosis and NVAF eligible for OACs (CHA<sub>2</sub>DS<sub>2</sub>-VASc score ≥2 [men] or ≥3 [women]). We calculated the yearly proportion of patients prescribed a direct OAC (DOAC), warfarin, or no OAC. We stratified by high-risk features (decompensated cirrhosis, thrombocytopenia, coagulopathy, chronic kidney disease, or end-stage renal disease). Among 32 487 patients (mean age=71.6 years, 38.5% women, 15.1% with decompensated cirrhosis, mean CHA<sub>2</sub>DS<sub>2</sub>-VASc=4.2), 44.6% used OACs within 180 days of NVAF diagnosis, including DOACs (20.2%) or warfarin (24.4%). Compared with OAC nonusers, OAC users were less likely to have decompensated cirrhosis (18.6% versus 10.7%), thrombocytopenia (19.5% versus 12.5%), or chronic kidney disease/end-stage renal disease (15.5% versus 14.0%). Between 2012 and 2019, warfarin use decreased by 21.0% (32.0% to 11.0%), whereas DOAC use increased by 30.6% (7.4% to 38.0%), and among all DOACs between 2012 and 2019, apixaban was the most commonly prescribed (46.1%). Warfarin use decreased and DOAC use increased in all subgroups, including in compensated and decompensated cirrhosis, thrombocytopenia, coagulopathy, chronic kidney disease/end-stage renal disease, and across CHA<sub>2</sub>DS<sub>2</sub>-VASc categories. Among OAC users (2012-2019), DOAC use increased by 58.9% (18.7% to 77.6%). Among DOAC users, the greatest proportional increase was with apixaban (61.2%; <i>P</i><0.001). <br /><b>Conclusions:</b><br/>Among US patients with cirrhosis and NVAF, DOAC use has increased substantially and surpassed warfarin, including in decompensated cirrhosis. Nevertheless, >55% of patients remain untreated, underscoring the need for clearer treatment guidance.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 10 Jan 2023:e026863; epub ahead of print</small></div>
Simon TG, Schneeweiss S, Singer DE, Sreedhara SK, Lin KJ
J Am Heart Assoc: 10 Jan 2023:e026863; epub ahead of print | PMID: 36625307
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<div><h4>Cause-Specific Mortality of Patients With Atrial Septal Defect and Up to 50 Years of Follow-Up.</h4><i>Muroke V, Jalanko M, Haukka J, Sinisalo J</i><br /><AbstractText><br /><b>Background:</b><br/>This study aimed to evaluate the long-term mortality and cause-specific mortality of patients with atrial septal defect (ASD) in a nationwide cohort. Methods and Results All patients diagnosed with simple ASD in the hospital discharge registry from 1969 to 2019 were included in the study. Complex congenital defects were excluded. Each subject was matched with 5 controls according to sex, age, and municipality at the index time. Adjusted mortality risk ratios (MRRs) were calculated using Poisson regression models. The median follow-up time was 11.1 years. Patients with ASD had higher overall mortality during follow-up, with an adjusted MRR of 1.72 (95% CI, 1.61-1.83). Patients with closed ASDs also had higher total mortality (MRR, 1.29 [95% CI, 1.10-1.51]). However, no difference in mortality was detected if the defect was closed before the age of 30 (MRR, 1.58 [95% CI, 0.90-2.77]), and transcatheter closed defects had lower mortality than the control cohort (MRR, 0.65 [95% CI, 0.42-0.99]). Patients with ASD had significantly more deaths due to congenital malformations (MRR, 54.61 [95% CI, 34.03-87.64]), other diseases of the circulatory system (MRR, 2.90 [95% CI, 2.42-3.49]), stroke (MRR, 1.89 [95% CI, 1.52-2.33]), diseases of the endocrine (MRR, 1.88 [95% CI, 1.10-3.22]) and respiratory system (MRR, 1.71 [95% CI, 1.19-2.45]), ischemic heart disease (MRR, 1.62 [95% CI, 1.41-1.86]), and accidents (MRR, 1.41 [95% CI, 1.05-1.89]). <br /><b>Conclusions:</b><br/>Patients with ASD had higher overall mortality compared with a matched general population cohort. Increased cause-specific mortality was seen in congenital malformations, stroke, and heart diseases.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 10 Jan 2023:e027635; epub ahead of print</small></div>
Muroke V, Jalanko M, Haukka J, Sinisalo J
J Am Heart Assoc: 10 Jan 2023:e027635; epub ahead of print | PMID: 36625312
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<div><h4>Preoperative Factors Predict Memory Decline After Coronary Artery Bypass Grafting or Percutaneous Coronary Intervention in an Epidemiological Cohort of Older Adults.</h4><i>Tang AB, Diaz-Ramirez LG, Smith AK, Lee SJ, Whitlock EL</i><br /><AbstractText><br /><b>Background:</b><br/>Durable memory decline may occur in older adults after surgical (coronary artery bypass grafting [CABG]) or nonsurgical (percutaneous coronary intervention) coronary revascularization. However, it is unknown whether individual memory risk can be predicted. We reanalyzed an epidemiological cohort of older adults to predict memory decline at ≈1 year after revascularization. Methods and Results We studied Health and Retirement Study participants who underwent CABG or percutaneous coronary intervention at age ≥65 years between 1998 and 2015 and participated in ≥1 biennial postprocedure assessment. Using a memory score based on direct and proxy cognitive tests, we identified participants whose actual postprocedure memory score was 1-2 (\"mild\") or >2 (\"major\") SDs below expected postprocedure performance. We modeled probability of memory decline using logistic regression on preoperatively known factors and evaluated model discrimination and calibration. A total of 1390 participants (551 CABG, 839 percutaneous coronary intervention) underwent CABG/percutaneous coronary intervention at 75±6 years old; 40% were women. The cohort was 83% non-Hispanic White, 8.4% non-Hispanic Black, 6.4% Hispanic ethnicity, and 1.7% from other groups masked by the HRS (Health and Retirement Study) to preserve participant confidentiality. At a median of 1.1 (interquartile range, 0.6-1.6) years after procedure, 267 (19%) had mild memory decline and 88 (6.3%) had major memory decline. Factors predicting memory decline included older age, frailty, and off-pump CABG; obesity was protective. The optimism-corrected area under the receiver operator characteristic curve was 0.73 (95% CI, 0.71-0.77). A cutoff of 50% probability of memory decline identified 14% of the cohort as high risk, and was 94% specific and 30% sensitive for late memory decline. <br /><b>Conclusions:</b><br/>Preoperative factors can be used to predict late memory decline after coronary revascularization in an epidemiological cohort with high specificity.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Dec 2022:e027849; epub ahead of print</small></div>
Tang AB, Diaz-Ramirez LG, Smith AK, Lee SJ, Whitlock EL
J Am Heart Assoc: 30 Dec 2022:e027849; epub ahead of print | PMID: 36583424
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<div><h4>Treatment and Implications of Vascular Endothelial Growth Factor Inhibitor-Induced Blood Pressure Rise: A Clinical Cohort Study.</h4><i>van Dorst DCH, Kabadayi S, Oomen-de Hoop E, Danser JAH, Mathijssen RHJ, Versmissen J</i><br /><AbstractText><br /><b>Background:</b><br/>Anti-cancer vascular endothelial growth factor inhibitors (VEGFI) frequently induce a rise in blood pressure (BP). The most effective treatment of this BP rise is currently unknown, and risk factors and its association with survival remain inconclusive. Methods and Results Baseline characteristics and BP readings were retrospectively collected from oncology patients who received oral VEGFI treatment (sorafenib, sunitinib, pazopanib, regorafenib, lenvatinib, or cabozantinib). Risk factors for a clinically relevant BP rise (increase of ≥20 mm Hg in systolic BP or ≥10 mm Hg in diastolic BP) were investigated via logistic regression (relative), efficacy of antihypertensives via unpaired t-tests, and association of BP rise with survival via Cox regression analysis. In total, 162 (47%) of 343 included patients developed a clinically relevant BP rise ≥7 days after VEGFI treatment initiation. Both calcium channel blockers and renin-angiotensin system inhibitors effectively reduced systolic BP (-24.1 and -18.2 mm Hg, respectively) and diastolic BP (-12.0 and -11.0 mm Hg, respectively). Pazopanib therapy (odds ratio, 2.71 [95% CI, 1.35-5.42; <i>P</i>=0.005], compared with sorafenib) and estimated glomerular filtration rate <60 mL/min per 1.73 m<sup>2</sup> (OR, 1.75 [95% CI, 0.99-3.18, <i>P</i>=0.054]) were risk factors for a BP rise, whereas a baseline BP ≥140/90 mm Hg associated with a lower risk (OR, 0.39 [95% CI, 0.25-0.62, <i>P</i><0.001]). Only for renal cell carcinoma, BP rise was associated with a substantially improved median overall survival compared with no BP rise: 45.4 versus 20.3 months, respectively, <i>P</i>=0.003. <br /><b>Conclusions:</b><br/>The type of VEGFI, baseline BP, and baseline estimated glomerular filtration rate determine the VEGFI-induced BP rise. Both calcium channel blockers and renin-angiotensin system inhibitors are effective antihypertensive treatments. Particularly in patients with renal cell carcinoma, a BP rise is associated with improved overall survival.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Dec 2022:e028050; epub ahead of print</small></div>
van Dorst DCH, Kabadayi S, Oomen-de Hoop E, Danser JAH, Mathijssen RHJ, Versmissen J
J Am Heart Assoc: 30 Dec 2022:e028050; epub ahead of print | PMID: 36583425
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<div><h4>Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke.</h4><i>Yu D, Liang N, Zebarth J, Shen Q, ... Swardfager W, ONDRI Investigators [Link]</i><br /><AbstractText><br /><b>Background:</b><br/>Cerebral small vessel disease is associated with higher ratios of soluble-epoxide hydrolase derived linoleic acid diols (12,13-dihydroxyoctadecenoic acid [DiHOME] and 9,10-DiHOME) to their parent epoxides (12(13)-epoxyoctadecenoic acid [EpOME] and 9(10)-EpOME); however, the relationship has not yet been examined in stroke. Methods and Results Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imaging criteria. Metabolites were quantified by ultra-high-performance liquid chromatography-mass spectrometry. Volumes of stroke, lacunes, white matter hyperintensities, magnetic resonance imaging visible perivascular spaces, and free water diffusion were quantified from structural and diffusion magnetic resonance imaging (3 Tesla). Adjusted linear regression models were used for analysis. Compared with participants with large vessel stroke (n=30), participants with small vessel stroke (n=50) had a higher 12,13-DiHOME/12(13)-EpOME ratio (β=0.251, <i>P</i>=0.023). The 12,13-DiHOME/12(13)-EpOME ratio was associated with more lacunes (β=0.266, <i>P</i>=0.028) but not with large vessel stroke volumes. Ratios of 12,13-DiHOME/12(13)-EpOME and 9,10-DiHOME/9(10)-EpOME were associated with greater volumes of white matter hyperintensities (β=0.364, <i>P</i><0.001; β=0.362, <i>P</i><0.001) and white matter MRI-visible perivascular spaces (β=0.302, <i>P</i>=0.011; β=0.314, <i>P</i>=0.006). In small vessel stroke, the 12,13-DiHOME/12(13)-EpOME ratio was associated with higher white matter free water diffusion (β=0.439, <i>P</i>=0.016), which was specific to the temporal lobe in exploratory regional analyses. The 9,10-DiHOME/9(10)-EpOME ratio was associated with temporal lobe atrophy (β=-0.277, <i>P</i>=0.031). <br /><b>Conclusions:</b><br/>Linoleic acid markers of cytochrome P450/soluble-epoxide hydrolase activity were associated with small versus large vessel stroke, with small vessel disease markers consistent with blood brain barrier and neurovascular-glial disruption, and temporal lobe atrophy. The findings may indicate a novel modifiable risk factor for small vessel disease and related neurodegeneration.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Dec 2022:e026901; epub ahead of print</small></div>
Yu D, Liang N, Zebarth J, Shen Q, ... Swardfager W, ONDRI Investigators [Link]
J Am Heart Assoc: 30 Dec 2022:e026901; epub ahead of print | PMID: 36583428
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<div><h4>Vessel Patency and Associated Factors of Drug-Coated Balloon for Femoropopliteal Lesion.</h4><i>Soga Y, Takahara M, Iida O, Tomoi Y, ... Ando K, POPCORN Investigators</i><br /><AbstractText><br /><b>Background:</b><br/>Although clinical trials have reported favorable outcomes after drug-coated balloon (DCB) therapy for femoropopliteal lesions, their real-world performance and predictors have not been well evaluated. This study aimed to elucidate 1-year freedom from restenosis and to explore the associated factors after a DCB for femoropopliteal lesions in clinical settings. Methods and Results This multicenter, prospective cohort registered 3165 de novo or restenotic femoropopliteallesions (mean lesion length, 13.5±9.3 cm; chronic total occlusion, 25.9%; severe calcification, 14.6%) that underwent successful DCB (Lutonix [24.2%] and IN.PACT Admiral [75.8%]) treatment between March 2018 and December 2019. Patency was assessed at 12±2 months. The primary outcome measure was 1-year freedom from restenosis and its associated factors. Bailout stenting was performed in 3.5% of patients. The postprocedural slow flow phenomenon was observed in 3.9% of patients. During a median follow-up of 14.2 months, 811 patients experienced restenosis. The Kaplan-Meier estimate of freedom from restenosis was 84.5% at 12 months (79.7% at 14 months). Focal, tandem, diffuse, and occlusive restenosis accounted for 37.4%, 9.8%, 18.9%, and 33.9%, respectively. Freedom from target lesion revascularization was 91.5% at 12 months. Risk factors independently associated with 1-year restenosis were a history of revascularization, smaller distal reference vessel diameter, severe calcification, chronic total occlusion, low-dose DCB, and residual stenosis. <br /><b>Conclusions:</b><br/>The 1-year clinical outcomes after DCB use for femoropopliteal lesions in real-world practice was favorable. The additive risk factors were associated with a lower rate of freedom from restenosis.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Dec 2022:e025677; epub ahead of print</small></div>
Soga Y, Takahara M, Iida O, Tomoi Y, ... Ando K, POPCORN Investigators
J Am Heart Assoc: 30 Dec 2022:e025677; epub ahead of print | PMID: 36583431
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<div><h4>Left Ventricular Apical Aneurysm in Fabry Disease: Implications for Clinical Significance and Risk Stratification.</h4><i>Chang HC, Kuo L, Sung SH, Weng CY, ... Chen SA, Yu WC</i><br /><AbstractText><br /><b>Background:</b><br/>A previously underrecognized phenotype of left ventricular apical aneurysm (LVAA) has been increasingly identified in Fabry disease. This study explored LVAA\'s clinical prevalence and its prognostic implications over a long-term follow-up. Methods and Results We retrospectively analyzed 268 consecutive patients with Fabry disease at a tertiary medical center. Patients with increased left ventricular mass index were recognized as having left ventricular hypertrophy (LVH). LVAA was identified using either echocardiography or cardiovascular magnetic resonance imaging. Two patients with ischemic LVAA were excluded. The primary end point was a composite of cardiovascular events, including heart failure hospitalization, sustained ventricular tachycardia, ischemic stroke, and all-cause mortality. Of 266 enrolled patients, 105 (39.5%) had LVH (age 58.5±11.9 years, 48.6% men), and 11 (10.5%) had LVAA. Over 49.3±34.8 months of follow-up, 25 patients with LVH experienced composite events, including 9 heart failure hospitalizations, 4 sustained ventricular tachycardia, 6 ischemic strokes, and 15 mortalities. In patients with LVH, those with LVAA had a significantly higher risk of composite events and lower event-free survival than those without LVAA (8 [72.7%] versus 17 [18.1%], log-rank <i>P</i><0.001). LVAA was independently associated with an increased risk of composite events (hazard ratio, 3.59 [95% CI, 1.30-9.91]; <i>P</i>=0.01) after adjusting for age, sex, advanced heart failure, renal function, dyslipidemia, atrial fibrillation, left ventricular ejection fraction, left ventricular diastolic function, and left ventricular mass index. <br /><b>Conclusions:</b><br/>LVAA is present in approximately 10% of patients with Fabry disease and LVH. It is associated with an increased risk of adverse cardiovascular events and may necessitate aggressive treatment.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Dec 2022:e027041; epub ahead of print</small></div>
Chang HC, Kuo L, Sung SH, Weng CY, ... Chen SA, Yu WC
J Am Heart Assoc: 30 Dec 2022:e027041; epub ahead of print | PMID: 36583432
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<div><h4>Femoral Vascular Closure Devices and Bleeding, Hemostasis, and Ambulation Following Percutaneous Coronary Intervention.</h4><i>Marquis-Gravel G, Boivin-Proulx LA, Huang Z, Zelenkofske SL, ... Alexander JH, Povsic TJ</i><br /><AbstractText><br /><b>Background:</b><br/>The effectiveness of vascular closure devices (VCDs) to reduce bleeding after transfemoral percutaneous coronary intervention remains unsettled. Methods and Results Participants in the REGULATE-PCI (Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention) trial who underwent transfemoral percutaneous coronary intervention with VCD implantation were compared with those who underwent manual compression. The primary effectiveness end point was type 2, 3, or 5 Bleeding Academic Research Consortium access site bleeding at day 3. Univariate and multivariate analyses were adjusted by the inverse probability weighting method using propensity score. Time to hemostasis and time to ambulation were compared between groups. Of the 1580 patients who underwent transfemoral percutaneous coronary intervention, 1004 (63.5%) underwent VCD implantation and 576 (36.5%) had manual compression. The primary effectiveness end point occurred in 64 (6.4%) participants in the VCD group and in 38 (6.6%) participants in the manual compression group (inverse probability weighting-adjusted odds ratio, 1.02 [95% CI, 0.77-1.36]; <i>P</i>=0.89). There were statistically significant 2-way interactions between VCD use and female sex, chronic kidney disease, and use of high-potency P2Y12 inhibition (ticagrelor or prasugrel) (<i>P</i><0.05 for all) with less bleeding with VCD use in these high-risk subgroups. Median time to hemostasis and time to ambulation were shorter in the VCD versus the manual compression group (<i>P</i><0.01 for both). <br /><b>Conclusions:</b><br/>Following transfemoral percutaneous coronary intervention, VCD use is associated with a shorter time to hemostasis and time to ambulation but not less bleeding. Further study of patients with high-bleeding risk is required, including women, patients with chronic kidney disease, and those using high-potency P2Y12 inhibitors. Registration URL: https://clinicaltrials.gov/ct2/show/NCT01848106; Unique identifier: NCT01848106.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Dec 2022:e025666; epub ahead of print</small></div>
Marquis-Gravel G, Boivin-Proulx LA, Huang Z, Zelenkofske SL, ... Alexander JH, Povsic TJ
J Am Heart Assoc: 30 Dec 2022:e025666; epub ahead of print | PMID: 36583436
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<div><h4>Canagliflozin Improves Myocardial Perfusion, Fibrosis, and Function in a Swine Model of Chronic Myocardial Ischemia.</h4><i>Sabe SA, Xu CM, Sabra M, Harris DD, ... Abid MR, Sellke FW</i><br /><AbstractText><br /><b>Background:</b><br/>Sodium-glucose cotransporter-2 inhibitors are cardioprotective independent of glucose control, as demonstrated in animal models of acute myocardial ischemia and clinical trials. The functional and molecular mechanisms of these benefits in the setting of chronic myocardial ischemia are poorly defined. The purpose of this study is to determine the effects of canagliflozin therapy on myocardial perfusion, fibrosis, and function in a large animal model of chronic myocardial ischemia. Methods and Results Yorkshire swine underwent placement of an ameroid constrictor to the left circumflex artery to induce chronic myocardial ischemia. Two weeks later, pigs received either no drug (n=8) or 300 mg sodium-glucose cotransporter-2 inhibitor canagliflozin orally, daily (n=8). Treatment continued for 5 weeks, followed by hemodynamic measurements, harvest, and tissue analysis. Canagliflozin therapy was associated with increased stroke volume and stroke work and decreased left ventricular stiffness compared with controls. The canagliflozin group had improved perfusion to ischemic myocardium compared with controls, without differences in arteriolar or capillary density. Canagliflozin was associated with decreased interstitial and perivascular fibrosis in chronically ischemic tissue, with reduced Jak/STAT (Janus kinase/signal transducer and activator of transcription) signaling compared with controls. In ischemic myocardium of the canagliflozin group, there was increased expression and activation of adenosine monophosphate-activated protein kinase, decreased activation of endothelial nitric oxide synthase, and unchanged total endothelial nitric oxide synthase. Canagliflozin therapy reduced total protein oxidation and increased expression of mitochondrial antioxidant superoxide dismutase 2 compared with controls. <br /><b>Conclusions:</b><br/>In the setting of chronic myocardial ischemia, canagliflozin therapy improves myocardial function and perfusion to ischemic territory, without changes in collateralization. Attenuation of fibrosis via reduced Jak/STAT signaling, activation of adenosine monophosphate-activated protein kinase, and antioxidant signaling may contribute to these effects.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Dec 2022:e028623; epub ahead of print</small></div>
Sabe SA, Xu CM, Sabra M, Harris DD, ... Abid MR, Sellke FW
J Am Heart Assoc: 30 Dec 2022:e028623; epub ahead of print | PMID: 36583437
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<div><h4>Prediction of Deterioration of Left Ventricular Function Using 3-Dimensional Speckle-Tracking Echocardiography in Patients With Left Bundle-Branch Block.</h4><i>Kim HM, Hwang IC, Yoon YE, Park JB, ... Lim Y, Cho GY</i><br /><AbstractText><br /><b>Background:</b><br/>Previous studies have demonstrated that 2-dimensional (2D) global longitudinal strain (GLS) is associated with cardiovascular outcomes in patients with left bundle-branch block. However, the predictive value of 3-dimensional (3D) speckle-tracking echocardiography has not yet been investigated in these patients. Methods and Results The authors retrospectively identified 290 patients with left bundle-branch block who underwent echocardiography more than twice. Using speckle-tracking echocardiography, 2D-GLS, 3D-GLS, 3D-global circumferential strain, 3D global radial strain, and 3D global area strain were acquired. The association between 2D and 3D strains and the follow-up left ventricular (LV) ejection fraction (LVEF) was analyzed. The study population was divided into 2 sets: a group with preserved LVEF (baseline LVEF ≥40%) and a group with reduced LVEF (baseline LVEF <40%). After a median follow-up of 29.1 months (interquartile range, 13.1-53.0 months), 14.9% of patients progressed to LV dysfunction in the group with preserved LVEF, and 51.0% of patients showed improved LV function in the group with reduced LVEF. Multivariable analysis of 2D and 3D strains revealed that higher 2D-GLS (odds ratio [OR], 0.65 [95% CI, 0.54-0.78], <i>P</i><0.001) was highly associated with maintaining LVEF in patients with preserved LVEF. However, a lower 3D-global circumferential strain (OR, 0.61 [95% CI, 0.47-0.78], <i>P</i><0.001) showed a strong association with persistently reduced LVEF in patients with reduced LVEF. <br /><b>Conclusions:</b><br/>Although 2D-GLS showed a powerful predictive value for the deterioration of LV function in the preserved LVEF group, 3D strain, especially 3D-global circumferential strain, can be helpful to predict consistent LV dysfunction in patients with left bundle-branch block who have reduced LVEF.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Dec 2022:e026194; epub ahead of print</small></div>
Kim HM, Hwang IC, Yoon YE, Park JB, ... Lim Y, Cho GY
J Am Heart Assoc: 30 Dec 2022:e026194; epub ahead of print | PMID: 36583438
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<div><h4>New Classification for the Combined Assessment of the Fractional Excretion of Urea Nitrogen and Estimated Plasma Volume Status in Acute Heart Failure.</h4><i>Nogi K, Ueda T, Nakamura T, Nogi M, ... Watanabe M, Saito Y</i><br /><AbstractText><br /><b>Background:</b><br/>The fractional excretion of urea nitrogen (FEUN) has been used as a renal blood flow index related to cardiac output, and the estimated plasma volume status (ePVS) as a body fluid volume index. However, the usefulness of their combination in acute decompensated heart failure (HF) management is unclear. We investigated the effect of 4 hemodynamic categories according to the high and low FEUN and ePVS values at discharge on the long-term prognosis of patients with acute decompensated HF. Methods and Results Between April 2011 and December 2018, we retrospectively identified 466 patients with acute decompensated HF with FEUN and ePVS values at discharge. Primary end point was postdischarge all-cause death. Secondary end points were (1) the composite of all-cause death and HF readmission, and (2) HF readmission in a time-to-event analysis. The patients were divided into 4 groups according to the high/low FEUN (≥35%, <35%) and ePVS (>5.5%, ≤5.5%) values at discharge: high-FEUN/low-ePVS, high-FEUN/high-ePVS, low-FEUN/low-ePVS, and low-FEUN/high-ePVS groups. During a median follow-up period of 28.1 months, there were 173 all-cause deaths (37.1%), 83 cardiovascular deaths (17.8%), and 121 HF readmissions (26.0%). The Kaplan-Meier curve analysis showed that the high-FEUN/low-ePVS group had a better prognosis than the other groups (log-rank test, <i>P</i><0.001). In the multivariable Cox regression analysis, the low-FEUN/high-ePVS group had a higher mortality than the high-FEUN/low-ePVS group (hazard ratio, 2.92 [95% CIs, 1.73-4.92; <i>P</i><0.001]). <br /><b>Conclusions:</b><br/>The new classification of the 4 hemodynamic profiles using the FEUN and ePVS values may play an important role in improving outcomes in patients with stable acute decompensated HF.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Dec 2022:e025596; epub ahead of print</small></div>
Nogi K, Ueda T, Nakamura T, Nogi M, ... Watanabe M, Saito Y
J Am Heart Assoc: 30 Dec 2022:e025596; epub ahead of print | PMID: 36583422
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<div><h4>Validation of a Brief Dietary Questionnaire for Use in Clinical Practice: Mini-EAT (Eating Assessment Tool).</h4><i>Lara-Breitinger KM, Medina Inojosa JR, Li Z, Kunzova S, ... Kopecky SL, Lopez-Jimenez F</i><br /><AbstractText><br /><b>Background:</b><br/>There is a scarcity of validated rapid dietary screening tools for patient use in the clinical setting to improve health and reduce cardiovascular risk. The Healthy Eating Index (HEI) 2015 measures compliance with the 2015 to 2020 Dietary Guidelines for Americans but requires completion of an extensive diet assessment to compute, which is time consuming and impractical. The authors hypothesize that a 19-item dietary survey assessing consumption of common food groups known to affect health will be correlated with the HEI-2015 assessed by a validated food frequency questionnaire and can be further reduced without affecting validity. Methods and Results A 19-item Eating Assessment Tool (EAT) of common food groups was created through literature review and expert consensus. A cross-sectional survey was then conducted in adult participants from a preventive cardiology clinic or cardiac rehabilitation and in healthy volunteers (n=661, mean age, 36 years; 76% women). Participants completed an online 156-item food frequency questionnaire, which was used to calculate the HEI score using standard methods. The association between each EAT question and HEI group was analyzed by Kruskal-Wallis test. Linear regression models were subsequently used to identify univariable and multivariable predictors for HEI score for further reduction in the number of items. The final 9-item model of Mini-EAT was validated by 5-fold cross validation. The 19-item EAT had a strong correlation with the HEI score (<i>r</i>=0.73) and was subsequently reduced to the 9 items independently predictive of the HEI score: fruits, vegetables, whole grains, refined grains, fish or seafood, legumes/nuts/seeds, low-fat dairy, high-fat dairy, and sweets consumption, without affecting the predictive ability of the tool (<i>r</i>=0.71). <br /><b>Conclusions:</b><br/>Mini-EAT is a 9-item validated brief dietary screener that correlates well with a comprehensive food frequency questionnaire. Future studies to test the Mini-EAT\'s validity in diverse populations and for development of clinical decision support systems to capture changes over time are needed.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 30 Dec 2022:e025064; epub ahead of print</small></div>
Lara-Breitinger KM, Medina Inojosa JR, Li Z, Kunzova S, ... Kopecky SL, Lopez-Jimenez F
J Am Heart Assoc: 30 Dec 2022:e025064; epub ahead of print | PMID: 36583423
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<div><h4>Shrunken Pore Syndrome: A New and More Powerful Phenotype of Renal Dysfunction Than Chronic Kidney Disease for Predicting Contrast-Associated Acute Kidney Injury.</h4><i>Zhang LW, Luo MQ, Xie XW, You ZB, ... Lin KY, Guo YS</i><br /><AbstractText><br /><b>Background:</b><br/>Shrunken pore syndrome (SPS) as a novel phenotype of renal dysfunction is characterized by a difference in renal filtration between cystatin C and creatinine. The manifestation of SPS was defined as a cystatin C-based estimated glomerular filtration rate (eGFR) <60% of the creatinine-based eGFR. SPS has been shown to be associated with the progression and adverse prognosis of various cardiovascular and renal diseases. However, the predictive value of SPS for contrast-associated acute kidney injury (CA-AKI) and long-term outcomes in patients undergoing percutaneous coronary intervention remains unclear. Methods and Results We retrospectively observed 5050 consenting patients from January 2012 to December 2018. Serum cystatin C and creatinine were measured and applied to corresponding 2012 and 2021 Chronic Kidney Disease Epidemiology Collaboration equations, respectively, to calculate the eGFR. Chronic kidney disease (CKD) was defined as a creatinine-based eGFR <60 mL/min per 1.73 m<sup>2</sup> without dialysis. CA-AKI was defined as an increase in serum creatinine ≥50% or 0.3 mg/dL within 48 hours after contrast medium exposure. Overall, 649 (12.85%) patients had SPS, and 324 (6.42%) patients developed CA-AKI. Multivariate logistic regression analysis indicated that SPS was significantly associated with CA-AKI after adjusting for potential confounding factors (odds ratio [OR], 4.17 [95% CI, 3.17-5.46]; <i>P</i><0.001). Receiver operating characteristic analysis indicated that the cystatin C-based eGFR:creatinine-based eGFR ratio had a better performance and stronger predictive power for CA-AKI than creatinine-based eGFR (area under the curve: 0.707 versus 0.562; <i>P</i><0.001). Multivariate logistic analysis revealed that compared with those without CKD and SPS simultaneously, patients with CKD and non-SPS (OR, 1.70 [95% CI, 1.11-2.55]; <i>P</i>=0.012), non-CKD and SPS (OR, 4.02 [95% CI, 2.98-5.39]; <i>P</i><0.001), and CKD and SPS (OR, 8.62 [95% CI, 4.67-15.7]; <i>P</i><0.001) had an increased risk of CA-AKI. Patients with both SPS and CKD presented the highest risk of long-term mortality compared with those without both (hazard ratio, 2.30 [95% CI, 1.38-3.86]; <i>P</i>=0.002). <br /><b>Conclusions:</b><br/>SPS is a new and more powerful phenotype of renal dysfunction for predicting CA-AKI than CKD and will bring new insights for an accurate clinical assessment of the risk of CA-AKI.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e027980; epub ahead of print</small></div>
Zhang LW, Luo MQ, Xie XW, You ZB, ... Lin KY, Guo YS
J Am Heart Assoc: 24 Dec 2022:e027980; epub ahead of print | PMID: 36565177
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<div><h4>Long-Term Clinical Outcomes in Patients With Severe Tricuspid Regurgitation.</h4><i>Nishiura N, Kitai T, Okada T, Sano M, ... Koyama T, Furukawa Y</i><br /><AbstractText><br /><b>Background:</b><br/>The natural history and optimal interventional timing in patients with isolated severe tricuspid regurgitation (TR) have not been well studied. This study aimed to investigate long-term clinical outcomes and risk factors associated with poor prognosis in patients with isolated severe TR. Methods and Results Consecutive transthoracic echocardiographic examinations in 2877 patients with isolated severe TR were retrospectively reviewed. Patients with significant left-sided valve disease or repeated examinations were excluded. Primary outcome was defined as a composite of all-cause death and hospitalization for heart failure. Among the 613 enrolled patients (mean age, 74±13 years; men, 38%), 141 died, and 62 were hospitalized for heart failure during the median follow-up period of 26.5 (interquartile range, 6.0-57.9) months. The 5-year event-free rate was 60.1%. TR pressure gradient (adjusted hazard ratio [HR], 1.03 [95% CI, 1.01-1.04]), blood urea nitrogen (adjusted HR, 1.02 [95% CI, 1.01-1.04]), left atrial volume index (adjusted HR, 1.01 [95% CI, 1.002-1.02]), and serum albumin (adjusted HR, 0.56 [95% CI, 0.36-0.95]) were identified as independent predictors of adverse events. A risk model based on the 4 clinical factors that included pulmonary hypertension (TR pressure gradient >40 mm Hg), elevated blood urea nitrogen levels (>25 mg/dL), decreased albumin levels (<3.7 g/dL), and left atrial enlargement (left atrial volume index <34 mL/m<sup>2</sup>) revealed a graded increase in the risk of adverse events (<i>P</i><0.001). <br /><b>Conclusions:</b><br/>The prognosis of isolated severe TR is not always favorable. Careful attention should be paid to patients with concomitant risk factors, such as pulmonary hypertension, elevated blood urea nitrogen levels, decreased albumin levels, and left atrial enlargement.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e025751; epub ahead of print</small></div>
Nishiura N, Kitai T, Okada T, Sano M, ... Koyama T, Furukawa Y
J Am Heart Assoc: 24 Dec 2022:e025751; epub ahead of print | PMID: 36565178
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<div><h4>Lifetime Burden of Morbidity in Patients With Isolated Congenital Ventricular Septal Defect.</h4><i>Eckerström F, Nyboe C, Redington A, Hjortdal VE</i><br /><AbstractText><br /><b>Background:</b><br/>The lifetime burden of morbidity in patients with isolated congenital ventricular septal defect (VSD) is not completely described. Methods and Results In a population-based cohort study in Denmark using nationwide medical registries, we included 8006 patients diagnosed with a congenital VSD before 2018 along with 79 568 randomly selected controls from the general Danish population matched by birth year and sex. Concomitant congenital cardiac malformations and chromosomal abnormalities were excluded. Cox proportional hazard regression, Fine and Gray competing risk regression, and Kaplan-Meier survival function were used to estimate burden of morbidity, compared with matched controls. Median follow-up was 23 years (interquartile range, 11-37 years). The hazard ratio (HR) of heart failure was high in both patients with unrepaired and surgically closed VSD when compared with their corresponding matched controls (5.4 [95% CI, 4.6-6.3] and 30.5 [95% CI, 21.8-42.7], respectively). Truncated analyses with time from birth until 1 year after VSD diagnosis (unrepaired) or surgery (surgically closed) censored revealed reduced but persisting late hazard of heart failure. Similarly, the late hazard of arrhythmias and pulmonary arterial hypertension was high irrespective of defect closure. The HR of endocarditis was 28.0 (95% CI, 19.2-40.9) in patients with unrepaired defect and 82.7 (95% CI, 37.5-183.2) in patients with surgically closed defect. The increased HR diminished after VSD surgery. In general, the incidence of morbidity among patients with unrepaired VSD accelerated after the age of 40 years. <br /><b>Conclusions:</b><br/>Patients with isolated congenital VSD carry a substantial burden of cardiovascular morbidity throughout life, irrespective of defect closure.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e027477; epub ahead of print</small></div>
Eckerström F, Nyboe C, Redington A, Hjortdal VE
J Am Heart Assoc: 24 Dec 2022:e027477; epub ahead of print | PMID: 36565179
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<div><h4>Urinary Sodium Excretion and Salt Intake Are Not Associated With Blood Pressure Variability in a White General Population.</h4><i>Zhou TL, Schütten MTJ, Kroon AA, Henry RMA, ... de Leeuw PW, Stehouwer CDA</i><br /><AbstractText><br /><b>Background:</b><br/>Salt restriction may lower blood pressure variability (BPV), but previous studies have shown inconsistent results. Therefore, we investigated in an observational study and intervention trial whether urinary sodium excretion and salt intake are associated with 24-hour BPV. Methods and Results We used data from the cross-sectional population-based Maastricht Study (n=2652; 60±8 years; 52% men) and from a randomized crossover trial (n=40; 49±11 years; 33% men). In the observational study, we measured 24-hour urinary sodium excretion and 24-hour BPV and performed linear regression adjusted for age, sex, mean blood pressure, lifestyle, and cardiovascular risk factors. In the intervention study, participants adhered to a 7-day low- and high-salt diet (50 and 250 mmol NaCl/24 h) with a washout period of 14 days, 24-hour BPV was measured during each diet. We used linear mixed models adjusted for order of diet, mean blood pressure, and body mass index. In the observational study, 24-hour urinary sodium excretion was not associated with 24-hour systolic or diastolic BPV (β, per 1 g/24 h urinary sodium excretion: 0.05 mm Hg [95% CI, -0.02 to 0.11] and 0.04 mm Hg [95% CI, -0.01 to 0.09], respectively). In the intervention trial, mean difference in 24-hour systolic and diastolic BPV between the low- and high-salt diet was not statistically significantly different (0.62 mm Hg [95% CI, -0.10 to 1.35] and 0.04 mm Hg [95% CI, -0.54 to 0.63], respectively). <br /><b>Conclusions:</b><br/>Urinary sodium excretion and salt intake are not independently associated with 24-hour BPV. These findings suggest that salt restriction is not an effective strategy to lower BPV in the White general population. Registration URL: https://clinicaltrials.gov/ct2/show/NCT02068781.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e026578; epub ahead of print</small></div>
Zhou TL, Schütten MTJ, Kroon AA, Henry RMA, ... de Leeuw PW, Stehouwer CDA
J Am Heart Assoc: 24 Dec 2022:e026578; epub ahead of print | PMID: 36565181
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<div><h4>Interaction of Blood Pressure and Glycemic Status in Developing Cardiovascular Disease: Analysis of a Nationwide Real-World Database.</h4><i>Suzuki Y, Kaneko H, Yano Y, Okada A, ... Yasunaga H, Komuro I</i><br /><AbstractText><br /><b>Background:</b><br/>Hypertension and diabetes frequently coexist. However, little is known about the interaction between high blood pressure (BP) and hyperglycemia in the development of cardiovascular disease (CVD). Methods and Results We conducted an observational cohort study that included 3 336 363 patients (median age, 43 years old; men, 57.2%). People taking BP- or glucose-lowering medications or those with prior history of CVD were excluded. We defined stage 1 hypertension as having systolic BP of 130 to 139 mm Hg or diastolic BP of 80 to 89 mm Hg and stage 2 hypertension as having systolic BP of ≥140 mm Hg or diastolic BP of ≥90 mm Hg. We defined prediabetes as having fasting plasma glucose of 100 to 125 mg/dL and diabetes as having fasting plasma glucose of ≥126 mg/dL. Over a mean follow-up period of 1185 ± 942 days, 5665 myocardial infarction, 52 475 angina pectoris, 25 436 stroke, 54 508 heart failure, and 12 932 atrial fibrillation events occurred. The BP and fasting plasma glucose categories additively increased the risk of myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. However, the relative risk of stage 1 and stage 2 hypertension developing into CVD was attenuated with deteriorating glycemic status. Similarly, the relative risk of prediabetes and diabetes developing into CVD was attenuated with increasing BP. For example, the relative risk reduction of stage 2 hypertension for heart failure was 53.5% in individuals with normal fasting plasma glucose, 46.4% in those with prediabetes, and 37.2% in those with diabetes. The robustness of our findings was confirmed using a multitude of sensitivity analyses. <br /><b>Conclusions:</b><br/>Although hypertension and hyperglycemia additively increase the risk of developing CVD, the relative contribution of hypertension to the development of CVD decreased with deteriorating glycemic status and that of hyperglycemia was attenuated with increasing BP. Our results indicate a potential interaction between hypertension and hyperglycemia in the development of CVD.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e026192; epub ahead of print</small></div>
Suzuki Y, Kaneko H, Yano Y, Okada A, ... Yasunaga H, Komuro I
J Am Heart Assoc: 24 Dec 2022:e026192; epub ahead of print | PMID: 36565182
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<div><h4>Characterization of Atrial Substrate to Predict the Success of Pulmonary Vein Isolation: The Prospective, Multicenter MASH-AF II (Multipolar Atrial Substrate High Density Mapping in Atrial Fibrillation) Study.</h4><i>Bergonti M, Spera FR, Ferrero TG, Nsahlai M, ... Rodríguez-Mañero M, Sarkozy A</i><br /><AbstractText><br /><b>Background:</b><br/>Left atrial substrate may have mechanistic relevance for ablation of atrial fibrillation (AF). We sought to analyze the relationship between low-voltage zones (LVZs), transition zones, and AF recurrence in patients undergoing pulmonary vein isolation. Methods and Results We conducted a prospective multicenter study on consecutive patients undergoing pulmonary vein isolation-only approach. LVZs and transition zones (0.5-1 mV) were analyzed offline on high-density electroanatomical maps collected before pulmonary vein isolation. Overall, 262 patients (61±11 years, 31% female) with paroxysmal (130 pts) or persistent (132 pts) AF were included. After 28 months of follow-up, 73 (28%) patients experienced recurrence. An extension of more than 5% LVZ in paroxysmal AF and more than 15% in persistent AF was associated with recurrence (hazard ratio [HR], 4.4 [95% CI, 2.0-9.8], <i>P</i><0.001 and HR, 1.9 [95% CI, 1.1-3.7], <i>P</i>=0.04, respectively). Significant association was found between LVZs and transition zones and between LVZs and left atrial volume index (LAVI) (both <i>P</i><0.001). Thirty percent of patients had significantly increased LAVI without LVZs. Eight percent of patients had LVZs despite normal LAVI. Older age, female sex, oncological history, and increased AF recurrence characterized the latter subgroup. <br /><b>Conclusions:</b><br/>In patients undergoing first pulmonary vein isolation, the impact of LVZs on outcomes occurs with lower burden in paroxysmal than persistent AF, suggesting that not all LVZs have equal prognostic implications. A proportional area of moderately decreased voltages accompanies LVZs, suggesting a continuous substrate instead of the dichotomous division of healthy or diseased tissue. LAVI generally correlates with LVZs, but a small subgroup of patients may present with disproportionate atrial remodeling, despite normal LAVI.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e027795; epub ahead of print</small></div>
Bergonti M, Spera FR, Ferrero TG, Nsahlai M, ... Rodríguez-Mañero M, Sarkozy A
J Am Heart Assoc: 24 Dec 2022:e027795; epub ahead of print | PMID: 36565183
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<div><h4>Association of Cardiovascular Health Score With Early- and Later-Onset Diabetes and With Subsequent Vascular Complications of Diabetes.</h4><i>Choi Y, Jacobs DR, Bancks MP, Lewis CE, ... Schreiner PJ, Duprez DA</i><br /><AbstractText><br /><b>Background:</b><br/>Little attention has been paid to how well the American Heart Association\'s cardiovascular health (CVH) score predicts early-onset diabetes in young adults. We investigated the association of CVH score with early- and later-onset diabetes and with subsequent complications of diabetes. <br /><b>Methods and results:</b><br/>Our sample included 4547 Black and White adults in the CARDIA (Coronary Artery Risk Development in Young Adults) study without diabetes at baseline (1985-1986; aged 18-30 years) with complete data on the CVH score at baseline, including smoking, body mass index, physical activity, diet quality, total cholesterol, blood pressure, and fasting blood glucose. Incident diabetes was determined based on fasting glucose, 2-hour postload glucose, hemoglobin A1c, or self-reported medication use throughout 8 visits for 30 years. Multinomial logistic regression was used to assess the association between CVH score and diabetes onset at age <40 years (early onset) versus age ≥40 years (later onset). Secondary analyses assessed the association between CVH score and risk of complications (coronary artery calcium, clinical cardiovascular disease, kidney function markers, diabetic retinopathy, and diabetic neuropathy) among a subsample with diabetes. We identified 116 early- and 502 later-onset incident diabetes cases. Each 1-point higher CVH score was associated with lower odds of developing early-onset (odds ratio [OR], 0.64 [95% CI, 0.58-0.71]) and later-onset diabetes (OR, 0.78 [95% CI, 0.74-0.83]). Lower estimates of diabetic complications were observed per 1-point higher CVH score: 19% for coronary artery calcification≥100, 18% for cardiovascular disease, and 14% for diabetic neuropathy. CONCLUSIONS Higher CVH score in young adulthood was associated with lower early- and later-onset diabetes as well as diabetic complications.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e027558; epub ahead of print</small></div>
Choi Y, Jacobs DR, Bancks MP, Lewis CE, ... Schreiner PJ, Duprez DA
J Am Heart Assoc: 24 Dec 2022:e027558; epub ahead of print | PMID: 36565184
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<div><h4>Epicardial Fat Volume, Cardiac Function, and Incident Heart Failure: The Rotterdam Study.</h4><i>Arshi B, Aliahmad HA, Ikram MA, Bos D, Kavousi M</i><br /><AbstractText><br /><b>Background:</b><br/>Larger epicardial fat volume (EFV) has been associated with increased risks of cardiovascular disease and atrial fibrillation. Yet, evidence on the association of EFV with cardiac function and incident heart failure (HF) remains scarce. Methods and Results We included 2103 participants (mean age, 68 years; 54.4% women) from the prospective population-based RS (Rotterdam Study) with computed tomography-based EFV and repeated echocardiography-based assessment of left ventricular (LV) systolic and diastolic function. Linear mixed effects and Cox-proportional hazard regression models, adjusted for cardiovascular risk factors, were used to assess the associations of EFV with repeated measurements of echocardiographic parameters and with incident HF. During a median follow-up of 9.7 years, 124 HF events occurred (incidence rate, 6.37 per 1000 person-years). For LV systolic function, 1-SD larger EFV was associated with 0.76 (95% CI, 0.54-0.98) mm larger LV end-diastolic dimension, 0.66 (95% CI, 0.47-0.85) mm larger LV end-systolic dimension, and 0.56% (95% CI, -0.86% to -0.27%) lower LV ejection fraction. Interactions between EFV and time were small. For LV diastolic function, 1-SD larger EFV was associated with 1.02 (95% CI, 0.78-1.27) mm larger left atrial diameter. Larger EFV was also associated with incident HF (hazard ratio per 1-SD increase in EFV, 1.34 [95% CI, 1.07-1.68] per 1-SD larger EFV). <br /><b>Conclusions:</b><br/>We report an independent association between EFV with new-onset HF in the general population. EFV seems to exert its influence on HF through different pathways contributing to deteriorations in systolic function and larger left atrial size in part, likely through mechanical restraint and hypertrophy.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e026197; epub ahead of print</small></div>
Arshi B, Aliahmad HA, Ikram MA, Bos D, Kavousi M
J Am Heart Assoc: 24 Dec 2022:e026197; epub ahead of print | PMID: 36565186
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<div><h4>Lipoprotein Subclasses Associated With High-Risk Coronary Atherosclerotic Plaque: Insights From the PROMISE Clinical Trial.</h4><i>McGarrah RW, Ferencik M, Giamberardino SN, Hoffmann U, ... Douglas PS, Shah SH</i><br /><AbstractText><br /><b>Background:</b><br/>More than half of major adverse cardiovascular events (MACE) occur in the absence of obstructive coronary artery disease and are often attributed to the rupture of high-risk coronary atherosclerotic plaque (HRP). Blood-based biomarkers that associate with imaging-defined HRP and predict MACE are lacking. <br /><b>Methods and results:</b><br/>Nuclear magnetic resonance-based lipoprotein particle profiling was performed in the biomarker substudy of the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial (N=4019) in participants who had stable symptoms suspicious for coronary artery disease. Principal components analysis was used to reduce the number of correlated lipoproteins into uncorrelated lipoprotein factors. The association of lipoprotein factors and individual lipoproteins of significantly associated factors with core laboratory determined coronary computed tomographic angiography features of HRP was determined using logistic regression models. The association of HRP-associated lipoproteins with MACE was assessed in the PROMISE trial and validated in an independent coronary angiography biorepository (CATHGEN [Catheterization Genetics]) using Cox proportional hazards models. Lipoprotein factors composed of high-density lipoprotein (HDL) subclasses were associated with HRP. In these factors, large HDL (odds ratio [OR], 0.70 [95% CI, 0.56-0.85]; <i>P</i><0.001) and medium HDL (OR, 0.84 [95% CI, 0.72-0.98]; <i>P</i>=0.028) and HDL size (OR, 0.82 [95% CI, 0.69-0.96]; <i>P</i>=0.018) were associated with HRP in multivariable models. Medium HDL was associated with MACE in PROMISE (hazard ratio [HR], 0.76 [95% CI, 0.63-0.92]; <i>P</i>=0.004), which was validated in the CATHGEN biorepository (HR, 0.91 [95% CI, 0.88-0.94]; <i>P</i><0.001). CONCLUSIONS Large and medium HDL subclasses and HDL size inversely associate with HRP features, and medium HDL subclasses inversely associate with MACE in PROMISE trial participants. These findings may aid in the risk stratification of individuals with chest pain and provide insight into the pathobiology of HRP. REGISTRATION URL: https://clinicaltrials.gov; Unique identifier: NCT01174550.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e026662; epub ahead of print</small></div>
McGarrah RW, Ferencik M, Giamberardino SN, Hoffmann U, ... Douglas PS, Shah SH
J Am Heart Assoc: 24 Dec 2022:e026662; epub ahead of print | PMID: 36565187
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<div><h4>On-Treatment Platelet Reactivity and Ischemic Outcomes in Patients With Diabetes Mellitus: Two-Year Results From ADAPT-DES.</h4><i>Shahim B, Redfors B, Stuckey TD, Liu M, ... Kirtane AJ, Stone GW</i><br /><AbstractText><br /><b>Background:</b><br/>Diabetes mellitus and high platelet reactivity (HPR) on clopidogrel are both associated with increased risk of ischemic events after percutaneous coronary intervention, but whether the HPR-associated risk of adverse ischemic events differs by diabetes mellitus status is unknown. Methods and Results ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of patients treated with coronary drug-eluting stents. HPR was defined as P2Y12 reaction units >208 by the VerifyNow point-of-care assay. Cox multivariable analysis was used to assess whether HPR-associated risk of major adverse cardiac events (MACE; cardiac death, myocardial infarction, or stent thrombosis) varied for patients with insulin-treated diabetes mellitus (ITDM), non-ITDM, and no diabetes mellitus. Diabetes mellitus and HPR were included in an interaction analysis. Of 8582 patients enrolled, 2429 (28.3%) had diabetes mellitus, of whom 998 (41.1%) had ITDM. Mean P2Y12 reaction units were higher in patients with diabetes mellitus versus without diabetes mellitus, and HPR was more frequent in patients with diabetes mellitus. HPR was associated with consistently increased 2-year rates of MACE in patients with and without diabetes mellitus (<i>P</i><sub>interaction</sub>=0.36). A significant interaction was present between HPR and non-insulin-treated diabetes mellitus versus ITDM for 2-year MACE (adjusted hazard ratio [HR] for non-ITDM, 2.28 [95% CI, 1.39-3.73] versus adjusted HR for ITDM, 1.02 [95% CI, 0.70-1.50]; <i>P</i><sub>interaction</sub>=0.01). <br /><b>Conclusions:</b><br/>HPR was more common in patients with diabetes mellitus and was associated with an increased risk of MACE in both patients with and without diabetes mellitus. In patients with diabetes mellitus, a more pronounced effect of HPR on MACE was present in lower-risk non-ITDM patients than in higher-risk patients with ITDM. Registration URL: https://clinicaltrials.gov/ct2/show/NCT00638794; Unique identifier: NCT00638794. ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents).</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e026482; epub ahead of print</small></div>
Shahim B, Redfors B, Stuckey TD, Liu M, ... Kirtane AJ, Stone GW
J Am Heart Assoc: 24 Dec 2022:e026482; epub ahead of print | PMID: 36565189
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<div><h4>Clinical Associations of Injuries Caused by Vasovagal Syncope: A Cohort Study From a Tertiary Syncope Unit.</h4><i>Tajdini M, Tavolinejad H, Aminorroaya A, Aryan Z, ... Kalhor P, Bozorgi A</i><br /><AbstractText><br /><b>Background:</b><br/>Recent research has revealed that vasovagal syncope (VVS) leads to a high incidence of injuries; however, clinical associations of injury are not well-established. We present data from an ongoing VVS cohort and aimed to determine characteristics associated with VVS-related injury. Methods and Results Between 2017 and 2020, consecutive patients ≥18 years of age presenting to a tertiary syncope unit and diagnosed with VVS were included. Clinical characteristics relevant to syncope were obtained for the index episode. The outcome was incidence of injury during VVS, documented by clinical evaluation at the syncope clinic. Among 1115 patients (mean age, 45.9 years; 48% women), 260 injuries (23%) occurred. History of VVS-related injuries (adjusted relative risk [aRR], 1.80 [95% CI, 1.42-2.29]), standing position (aRR, 1.34 [95% CI, 1.06-1.68]), and female sex (aRR, 1.30 [95% CI, 1.06-1.60]) were associated with injury, whereas recurrent VVS (aRR, 0.63 [95% CI, 0.49-0.81]) and syncope in the noon/afternoon (aRR, 0.70 [95% CI, 0.56-0.87]) and evening/night (aRR, 0.43 [95% CI, 0.33-0.57]) compared with morning hours were associated with lower risk. There was a trend for higher rates of injury with overweight/obesity (aRR, 1.23 [95% CI, 0.99-1.54]) and syncope occurring at home (aRR, 1.22 [95% CI, 0.98-1.51]). In a per-syncope analysis considering up to 3 previous episodes (n=2518, 36% traumatic), syncope at home (aRR, 1.33 [95% CI, 1.17-1.51]) and absence of prodromes (aRR, 1.34 [95% CI, 1.09-1.61]) were associated with injury. <br /><b>Conclusions:</b><br/>Patient characteristics, VVS presentations, the circumstances, and surroundings can determine the risk of injury. These associations of VVS-related injury identify at-risk individuals and high-risk situations. Future prospective studies are needed to investigate potential strategies for prevention of post-VVS injury in recurrent cases.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e027272; epub ahead of print</small></div>
Tajdini M, Tavolinejad H, Aminorroaya A, Aryan Z, ... Kalhor P, Bozorgi A
J Am Heart Assoc: 24 Dec 2022:e027272; epub ahead of print | PMID: 36565190
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<div><h4>Predicting Arterial Thrombotic Events Following Peripheral Revascularization Using Objective Viscoelastic Data.</h4><i>Majumdar M, Hall RP, Feldman Z, Goudot G, ... Eagleton M, Dua A</i><br /><AbstractText><br /><b>Background:</b><br/>Peripheral artery disease is endemic in our globally aging population, with >200 million affected worldwide. Graft/stent thrombosis after revascularization is common and frequently results in amputation, major adverse cardiovascular events, and cardiovascular mortality. Optimizing medications to decrease thrombosis is of paramount importance; however, limited guidance exists on how to use and monitor antithrombotic therapy in this heterogeneous population. Thromboelastography with platelet mapping (TEG-PM) provides comprehensive coagulation metrics and may be integral to the next stage of patient-centered thrombophrophylaxis. This prospective study aimed to determine if TEG-PM could predict subacute graft/stent thrombosis following lower extremity revascularization, and if objective cut point values could be established to identify those high-risk patients. Methods and Results We conducted a single-center prospective observational study of patients undergoing lower extremity revascularization. Patients were followed up for the composite end point postoperative graft/stent thrombosis at 1 year. TEG-PM analysis of the time point before thrombosis in the event group was compared with the last postoperative visit in the nonevent group. Cox proportional hazards analysis examined the association of TEG-PM metrics to thrombosis. Cut point analysis explored the predictive capacity of TEG-PM metrics for those at high risk. A total of 162 patients were analyzed, of whom 30 (18.5%) experienced graft/stent thrombosis. Patients with thrombosis had significantly greater platelet aggregation (79.7±15.7 versus 58.5±26.4) and lower platelet inhibition (20.7±15.6% versus 41.1±26.6%) (all <i>P</i><0.01). Cox proportional hazards analysis revealed that for every 1% increase in platelet aggregation, the hazard of experiencing an event during the study period increased by 5% (hazard ratio, 1.05 [95% CI, 1.02-1.07]; <i>P</i><0.01). An optimal cut point of >70.8% platelet aggregation and/or <29.2% platelet inhibition identifies those at high risk of thrombosis with 87% sensitivity and 70% to 71% specificity. <br /><b>Conclusions:</b><br/>Among patients undergoing lower extremity revascularization, increased platelet reactivity was predictive of subacute postoperative graft/stent thrombosis. On the basis of the cut points of >70.8% platelet aggregation and <29.2% platelet inhibition, consideration of an alternative or augmented antithrombotic regimen for high-risk patients may decrease the risk of postoperative thrombotic events.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e027790; epub ahead of print</small></div>
Majumdar M, Hall RP, Feldman Z, Goudot G, ... Eagleton M, Dua A
J Am Heart Assoc: 24 Dec 2022:e027790; epub ahead of print | PMID: 36565191
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<div><h4>Protective Role of Endothelial Fibulin-4 in Valvulo-Arterial Integrity.</h4><i>Nguyen TAV, Lino CA, Hang HT, Alves JV, ... Yamashiro Y, Yanagisawa H</i><br /><AbstractText><br /><b>Background:</b><br/>Homeostasis of the vessel wall is cooperatively maintained by endothelial cells (ECs), smooth muscle cells, and adventitial fibroblasts. The genetic deletion of fibulin-4 (<i>Fbln4</i>) in smooth muscle cells (<i>SMKO</i>) leads to the formation of thoracic aortic aneurysms with the disruption of elastic fibers. Although <i>Fbln4</i> is expressed in the entire vessel wall, its function in ECs and relevance to the maintenance of valvulo-arterial integrity are not fully understood. Methods and Results Gene silencing of <i>FBLN4</i> was conducted on human aortic ECs to evaluate morphological changes and gene expression profile. <i>Fbln4</i> double knockout (<i>DKO</i>) mice in ECs and smooth muscle cells were generated and subjected to histological analysis, echocardiography, Western blotting, RNA sequencing, and immunostaining. An evaluation of the thoracic aortic aneurysm phenotype and screening of altered signaling pathways were performed. Knockdown of <i>FBLN4</i> in human aortic ECs induced mesenchymal cell-like changes with the upregulation of mesenchymal genes, including <i>TAGLN</i> and <i>MYL9</i>. <i>DKO</i> mice showed the exacerbation of thoracic aortic aneurysms when compared with those of <i>SMKO</i> and upregulated Thbs1, a mechanical stress-responsive molecule, throughout the aorta. <i>DKO</i> mice also showed progressive aortic valve thickening with collagen deposition from postnatal day 14, as well as turbulent flow in the ascending aorta. Furthermore, RNA sequencing and immunostaining of the aortic valve revealed the upregulation of genes involved in endothelial-to-mesenchymal transition, inflammatory response, and tissue fibrosis in <i>DKO</i> valves and the presence of activated valve interstitial cells. <br /><b>Conclusions:</b><br/>The current study uncovers the pivotal role of endothelial fibulin-4 in the maintenance of valvulo-arterial integrity, which influences thoracic aortic aneurysm progression.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e026942; epub ahead of print</small></div>
Nguyen TAV, Lino CA, Hang HT, Alves JV, ... Yamashiro Y, Yanagisawa H
J Am Heart Assoc: 24 Dec 2022:e026942; epub ahead of print | PMID: 36565192
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<div><h4>Coronary Slow Flow Is Not Diagnostic of Microvascular Dysfunction in Patients With Angina and Unobstructed Coronary Arteries.</h4><i>Dutta U, Sinha A, Demir OM, Ellis H, Rahman H, Perera D</i><br /><AbstractText><br /><b>Background:</b><br/>Guidelines recommend that coronary slow flow phenomenon (CSFP), defined as corrected thrombolysis in myocardial infarction frame count (CTFC) <mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\"><mml:semantics><mml:mrow><mml:mo>></mml:mo></mml:mrow><mml:annotation>$$ > $$</mml:annotation></mml:semantics></mml:math>27, can diagnose coronary microvascular dysfunction (CMD) in patients with angina and nonobstructed coronary arteries. CSFP has also historically been regarded as a sign of coronary endothelial dysfunction (CED). We sought to validate the utility of CTFC, as a binary classifier of CSFP and as a continuous variable, to diagnose CMD and CED. Methods and Results Patients with angina and nonobstructed coronary arteries had simultaneous coronary pressure and flow velocity measured using a dual sensor-tipped guidewire during rest, adenosine-mediated hyperemia, and intracoronary acetylcholine infusion. CMD was defined as the inability to augment coronary blood flow in response to adenosine (coronary flow reserve <2.5) and CED in response to acetylcholine (acetylcholine flow reserve ≤1.5); 152 patients underwent assessment using adenosine, of whom 82 underwent further acetylcholine testing. Forty-six patients (30%) had CSFP, associated with lower flow velocity and higher microvascular resistance as compared with controls (16.5<mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\"><mml:semantics><mml:mrow><mml:mo>±</mml:mo></mml:mrow><mml:annotation>$$ \\pm $$</mml:annotation></mml:semantics></mml:math>6.9 versus 20.2<mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\"><mml:semantics><mml:mrow><mml:mo>±</mml:mo></mml:mrow><mml:annotation>$$ \\pm $$</mml:annotation></mml:semantics></mml:math>6.9 cm/s; <i>P</i>=0.001 and 6.26<mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\"><mml:semantics><mml:mrow><mml:mo>±</mml:mo></mml:mrow><mml:annotation>$$ \\pm $$</mml:annotation></mml:semantics></mml:math>1.83 versus 5.36<mml:math xmlns:mml=\"http://www.w3.org/1998/Math/MathML\"><mml:semantics><mml:mrow><mml:mo>±</mml:mo></mml:mrow><mml:annotation>$$ \\pm $$</mml:annotation></mml:semantics></mml:math>1.83 mm Hg/cm/s; <i>P</i>=0.009, respectively). However, as a diagnostic test, CSFP had poor sensitivity and specificity for both CMD (26.7% and 65.2%) and CED (21.1% and 56.0%). Furthermore, on receiver operating characteristics analyses, CTFC could not predict CMD or CED (area under the curve, 0.41 [95% CI, 0.32%-0.50%] and 0.36 [95% CI, 0.23%-0.49%], respectively). <br /><b>Conclusions:</b><br/>In patients with angina and nonobstructed coronary arteries, CSFP and CTFC are not diagnostic of CMD or CED. Guidelines supporting the use of CTFC in the diagnosis of CMD should be revisited.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e027664; epub ahead of print</small></div>
Dutta U, Sinha A, Demir OM, Ellis H, Rahman H, Perera D
J Am Heart Assoc: 24 Dec 2022:e027664; epub ahead of print | PMID: 36565193
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<div><h4>Social Deprivation and Post-TAVR Outcomes in Ontario, Canada: A Population-Based Study.</h4><i>Patel RV, Ravindran M, Qiu F, Manoragavan R, ... Mamas MA, Wijeysundera HC</i><br /><AbstractText><br /><b>Background:</b><br/>Transcatheter aortic valve replacement (TAVR)/intervention has become the standard of care for treatment of severe aortic stenosis across the spectrum of risk. There are socioeconomic disparities in access to TAVR. The impact of these disparities on postprocedural outcomes remains unknown. Our objective was to examine the association between neighborhood-level social deprivation and post-TAVR mortality and hospital readmission. Methods and Results We conducted a population-based retrospective cohort study of all 4145 patients in Ontario, Canada, who received TAVR from April 1, 2017, to March 31, 2020. Our co-primary outcomes were 1-year postprocedure mortality and 1-year postprocedure readmission. Using Cox proportional hazards models for mortality and cause-specific competing risk hazard models for readmission, we evaluated the relationship between neighborhood-level measures of residential instability, material deprivation, and concentration of racial and ethnic groups with post-TAVR outcomes. After multivariable adjustment, we found a statistically significant relationship between residential instability and postprocedural 1-year mortality, ranging from a hazard ratio of 1.64 to a hazard ratio of 2.05. There was a significant association between the highest degree of residential instability and 1-year readmission (hazard ratio, 1.23 [95% CI, 1.01-1.49]). There was no association between material deprivation and concentration of racial and ethnic groups with post-TAVR outcomes. <br /><b>Conclusions:</b><br/>Residential instability was associated with increased risk for post-TAVR mortality, and the highest quintile of residential instability was associated with increased post-TAVR readmission. To reduce health disparities and promote an equitable health care system, further research and policy interventions will be required to identify and support economically and socially minoritized patients undergoing TAVR.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e028144; epub ahead of print</small></div>
Patel RV, Ravindran M, Qiu F, Manoragavan R, ... Mamas MA, Wijeysundera HC
J Am Heart Assoc: 24 Dec 2022:e028144; epub ahead of print | PMID: 36565194
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<div><h4>Initial Antihypertensive Regimens in Newly Treated Patients: Real World Evidence From the OneFlorida+ Clinical Research Network.</h4><i>Smith SM, Winterstein AG, Gurka MJ, Walsh MG, ... Pepine CJ, Cooper-DeHoff RM</i><br /><AbstractText><br /><b>Background:</b><br/>Knowledge of real-world antihypertensive use is limited to prevalent hypertension, limiting our understanding of how treatment evolves and its contribution to persistently poor blood pressure control. We sought to characterize antihypertensive initiation among new users. Methods and Results Using Medicaid and Medicare data from the OneFlorida+ Clinical Research Consortium, we identified new users of ≥1 first-line antihypertensives (angiotensin-converting enzyme inhibitor, calcium channel blocker, angiotensin receptor blocker, thiazide diuretic, or β-blocker) between 2013 and 2021 among adults with diagnosed hypertension, and no antihypertensive fill during the prior 12 months. We evaluated initial antihypertensive regimens by class and drug overall and across study years and examined variation in antihypertensive initiation across demographics (sex, race, and ethnicity) and comorbidity (chronic kidney disease, diabetes, and atherosclerotic cardiovascular disease). We identified 143 054 patients initiating 188 995 antihypertensives (75% monotherapy; 25% combination therapy), with mean age 59 years and 57% of whom were women. The most commonly initiated antihypertensive class overall was angiotensin-converting enzyme inhibitors (39%) followed by β-blockers (31%), calcium channel blockers (24%), thiazides (19%), and angiotensin receptor blockers (11%). With the exception of β-blockers, a single drug accounted for ≥75% of use of each class. β-blocker use decreased (35%-26%), and calcium channel blocker use increased (24%-28%) over the study period, while initiation of most other classes remained relatively stable. We also observed significant differences in antihypertensive selection across demographic and comorbidity strata. <br /><b>Conclusions:</b><br/>These findings indicate that substantial variation exists in initial antihypertensive prescribing, and there remain significant gaps between current guideline recommendations and real-world implementation in early hypertension care.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e026652; epub ahead of print</small></div>
Smith SM, Winterstein AG, Gurka MJ, Walsh MG, ... Pepine CJ, Cooper-DeHoff RM
J Am Heart Assoc: 24 Dec 2022:e026652; epub ahead of print | PMID: 36565195
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<div><h4>Proteolytic Degradation Is a Major Contributor to Bioprosthetic Heart Valve Failure.</h4><i>Kostyunin AE, Glushkova TV, Lobov AA, Ovcharenko EA, ... Barbarash LS, Kutikhin AG</i><br /><AbstractText><br /><b>Background:</b><br/>Whereas the risk factors for structural valve degeneration (SVD) of glutaraldehyde-treated bioprosthetic heart valves (BHVs) are well studied, those responsible for the failure of BHVs fixed with alternative next-generation chemicals remain largely unknown. This study aimed to investigate the reasons behind the development of SVD in ethylene glycol diglycidyl ether-treated BHVs. Methods and Results Ten ethylene glycol diglycidyl ether-treated BHVs excised because of SVD, and 5 calcified aortic valves (AVs) replaced with BHVs because of calcific AV disease were collected and their proteomic profile was deciphered. Then, BHVs and AVs were interrogated for immune cell infiltration, microbial contamination, distribution of matrix-degrading enzymes and their tissue inhibitors, lipid deposition, and calcification. In contrast with dysfunctional AVs, failing BHVs suffered from complement-driven neutrophil invasion, excessive proteolysis, unwanted coagulation, and lipid deposition. Neutrophil infiltration was triggered by an asymptomatic bacterial colonization of the prosthetic tissue. Neutrophil elastase, myeloblastin/proteinase 3, cathepsin G, and matrix metalloproteinases (MMPs; neutrophil-derived MMP-8 and plasma-derived MMP-9), were significantly overexpressed, while tissue inhibitors of metalloproteinases 1/2 were downregulated in the BHVs as compared with AVs, together indicative of unbalanced proteolysis in the failing BHVs. As opposed to other proteases, MMP-9 was mostly expressed in the disorganized prosthetic extracellular matrix, suggesting plasma-derived proteases as the primary culprit of SVD in ethylene glycol diglycidyl ether-treated BHVs. Hence, hemodynamic stress and progressive accumulation of proteases led to the extracellular matrix degeneration and dystrophic calcification, ultimately resulting in SVD. <br /><b>Conclusions:</b><br/>Neutrophil- and plasma-derived proteases are responsible for the loss of BHV mechanical competence and need to be thwarted to prevent SVD.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e028215; epub ahead of print</small></div>
Kostyunin AE, Glushkova TV, Lobov AA, Ovcharenko EA, ... Barbarash LS, Kutikhin AG
J Am Heart Assoc: 24 Dec 2022:e028215; epub ahead of print | PMID: 36565196
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<div><h4>Combination of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as a Novel Predictor of Cardiac Death in Patients With Acute Decompensated Heart Failure With Preserved Left Ventricular Ejection Fraction: A Multicenter Study.</h4><i>Tamaki S, Nagai Y, Shutta R, Masuda D, ... Sakata Y, OCVC‐Heart Failure Investigators</i><br /><AbstractText><br /><b>Background:</b><br/>Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are novel inflammation markers. Their combined usefulness for estimating the prognosis of patients with heart failure with preserved ejection fraction (HFpEF) admitted for acute decompensated heart failure remains elusive. Methods and Results We investigated 1026 patients registered in the Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction. Both NLR and PLR values were measured at the time of admission. Comorbidity burden was defined as the number of occurrences of 8 common comorbidities of HFpEF. The primary end point was cardiac death. The patients were stratified into 3 groups based on the optimal cut-off values of NLR and PLR on the receiver operating characteristic curve analysis for predicting cardiac death (low NLR and PLR, either high NLR or PLR, and both high NLR and PLR). After a median follow-up of 429 days, 195 patients died, with 85 of these deaths attributed to cardiac causes. An increased comorbidity burden was significantly associated with a higher proportion of patients with high NLR (>4.5) or PLR (>193), or both. High NLR and PLR values were independently associated with cardiac death, and a combination of both values was the strongest predictor (hazard ratio, 2.66 [95% CI, 1.51%-4.70%], <i>P</i>=0.0008). A significant difference was found in the rate of cardiac death among the 3 groups stratified by NLR and PLR values. <br /><b>Conclusions:</b><br/>The combination of NLR and PLR is useful for the prediction of postdischarge cardiac death in patients with acute HFpEF. Registration URL: ClinicalTrials.gov; Unique identifier: UMIN000021831.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e026326; epub ahead of print</small></div>
Tamaki S, Nagai Y, Shutta R, Masuda D, ... Sakata Y, OCVC‐Heart Failure Investigators
J Am Heart Assoc: 24 Dec 2022:e026326; epub ahead of print | PMID: 36565197
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<div><h4>Biomarker Concentrations and Their Temporal Changes in Patients With Myocardial Infarction and Nonobstructive Compared With Obstructive Coronary Arteries: Results From the PLATO Trial.</h4><i>Hjort M, Eggers KM, Lakic TG, Lindbäck J, ... Lindahl B, PLATO trial investigators*</i><br /><AbstractText><br /><b>Background:</b><br/>The pathobiology of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is often uncertain. Investigating biomarker concentrations and their changes may offer novel pathophysiological insights. Methods and Results In this post hoc study of the PLATO (Platelet Inhibition and Patient Outcomes) trial, concentrations of hs-cTnT (high-sensitivity cardiac troponin T), NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-CRP (high-sensitivity C-reactive protein), and GDF-15 (growth differentiation factor 15) were measured in patients with MINOCA at baseline (n=554) and at 1-month follow-up (n=107). For comparisons, biomarkers were also measured in patients with MI with obstructive (stenosis ≥50%) coronary artery disease (baseline: n=11 106; follow-up: n=2755]). Adjusted linear regression models were used to compare concentrations and their short- and long-term changes. The adjusted geometric mean ratios (GMRs) in patients with MINOCA (median age, 61 years; 50.4% women) indicated lower hs-cTnT (GMR, 0.77 [95% CI, 0.68-0.88]) but higher hs-CRP (GMR, 1.21 [95% CI, 1.08-1.37]) and GDF-15 concentrations (GMR, 1.06 [95% CI, 1.02-1.11]) at baseline compared with patients with MI with obstructive coronary artery disease, whereas NT-proBNP concentrations were similar. Temporal decreases in hs-cTnT, NT-proBNP, and hs-CRP concentrations until 1-month follow-up were more pronounced in patients with MINOCA. At follow-up, patients with MINOCA had lower concentrations of hs-cTnT (GMR, 0.71 [95% CI, 0.60-0.84]), NT-proBNP (GMR, 0.45 [95% CI, 0.36-0.56]), and hs-CRP (GMR, 0.68 [95% CI, 0.53-0.86]). One-month GDF-15 concentrations were similar between both groups with MI. <br /><b>Conclusions:</b><br/>Biomarker concentrations suggest greater initial inflammatory activity, similar degree of myocardial dysfunction, and less pronounced myocardial injury during the acute phase of MINOCA compared with MI with obstructive coronary artery disease but also faster myocardial recovery. Registration URL: http://www.clinicaltrials.gov; Unique identifier: NCT00391872.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e027466; epub ahead of print</small></div>
Hjort M, Eggers KM, Lakic TG, Lindbäck J, ... Lindahl B, PLATO trial investigators*
J Am Heart Assoc: 24 Dec 2022:e027466; epub ahead of print | PMID: 36565198
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<div><h4>Impact of Empagliflozin in Heart Failure With Reduced Ejection Fraction in Patients With Ischemic Versus Nonischemic Cause.</h4><i>Khan MS, Butler J, Anker SD, Filippatos G, ... Zannad F, Packer M</i><br /><AbstractText><br /><b>Background:</b><br/>Outcomes and treatment effects of therapy may vary according to the cause of heart failure (HF). Methods and Results In this post hoc analysis of the EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction) trial, the effect of empagliflozin on cardiovascular and renal outcomes was assessed according to the cause of HF. The cause of HF was investigator reported and stratified as ischemic or nonischemic. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs. Of the 3730 patients enrolled, 1929 (51.7%) had ischemic cause. In the placebo arm, patients with ischemic cause of HF did not have a significantly higher risk of cardiovascular mortality (HR, 1.21 [95% CI, 0.90-1.63]) and hospitalization for HF (HR, 0.90 [95% CI, 0.72-1.12]) compared with nonischemic cause. Empagliflozin compared with placebo significantly reduced the risk of cardiovascular death or hospitalization for HF in patients with ischemic and nonischemic cause (HR, 0.82 [95% CI, 0.68-0.99] for ischemic and HR, 0.67 [95% CI, 0.55-0.82] for nonischemic cause; <i>P</i> interaction=0.15). The benefit of empagliflozin on HF hospitalization, the renal composite end point, estimated glomerular filtration slope changes, and health status scores were also consistent in both groups without treatment by cause modification. <br /><b>Conclusions:</b><br/>Empagliflozin offers cardiovascular and renal benefits in patients with heart failure with reduced ejection fraction regardless of the cause of HF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e027652; epub ahead of print</small></div>
Khan MS, Butler J, Anker SD, Filippatos G, ... Zannad F, Packer M
J Am Heart Assoc: 24 Dec 2022:e027652; epub ahead of print | PMID: 36565199
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<div><h4>Ross Procedure Versus Mechanical Versus Bioprosthetic Aortic Valve Replacement: A Network Meta-Analysis.</h4><i>Yokoyama Y, Kuno T, Toyoda N, Fujisaki T, ... El-Hamamsy I, Fukuhara S</i><br /><AbstractText><br /><b>Background:</b><br/>The Ross operation appears to restore normal survival in young and middle-aged adults with aortic valve disease. However, there are limited data comparing it with conventional aortic valve replacement. Herein, we compared outcomes of the Ross procedure with mechanical and bioprosthetic aortic valve replacement (M-AVR and B-AVR, respectively). Methods and Results MEDLINE and EMBASE were searched through March 2022 to identify randomized controlled trials and propensity score-matched studies that investigated outcomes of patients aged ≥16 years undergoing the Ross procedure, M-AVR, or B-AVR. The systematic literature search identified 2 randomized controlled trials and 8 propensity score-matched studies involving a total of 4812 patients (Ross: n=1991; M-AVR: n=2019; and B-AVR: n=802). All-cause mortality was significantly lower in the Ross procedure group compared with M-AVR (hazard ratio [HR] [95% CI], 0.58 [0.35-0.97]; <i>P</i>=0.035) and B-AVR (HR [95% CI], 0.32 [0.18-0.59]; <i>P</i><0.001) groups. The reintervention rate was lower after the Ross procedure and M-AVR compared with B-AVR, whereas it was higher after the Ross procedure compared with M-AVR. Major bleeding rate was lower after the Ross procedure compared with M-AVR. Long-term stroke rate was lower following the Ross procedure compared with M-AVR and B-AVR. The rate of endocarditis was also lower after the Ross procedure compared with B-AVR. <br /><b>Conclusions:</b><br/>Improved long-term outcomes of the Ross procedure are demonstrated compared with conventional M-AVR and B-AVR options. These results highlight a need to enhance the recognition of the Ross procedure and revisit current guidelines on the optimal valve substitute for young and middle-aged patients.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e8066; epub ahead of print</small></div>
Yokoyama Y, Kuno T, Toyoda N, Fujisaki T, ... El-Hamamsy I, Fukuhara S
J Am Heart Assoc: 24 Dec 2022:e8066; epub ahead of print | PMID: 36565200
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<div><h4>Impact of Race and Ethnicity on Use and Outcomes of Septal Reduction Therapies for Obstructive Hypertrophic Cardiomyopathy.</h4><i>Patlolla SH, Schaff HV, Nishimura RA, Eleid MF, Geske JB, Ommen SR</i><br /><AbstractText><br /><b>Background:</b><br/>Information on impact of race and ethnicity on use and early outcomes of septal reduction therapies (SRTs) for obstructive hypertrophic obstructive cardiomyopathy are limited. Methods and Results Using the National Inpatient Sample from January 2012 through December 2019, we identified all adult admissions with a primary diagnosis of obstructive hypertrophic cardiomyopathy and those undergoing SRT. Predictors of receiving SRT and outcomes including in-hospital mortality, complications, and resource use were evaluated in racial and ethnic groups. Among a total of 18 895 adult admissions with obstructive hypertrophic cardiomyopathy, SRT was performed in 7255 (38.4%) admissions. Septal myectomy was performed in 4930 (26.1%), while alcohol septal ablation was performed in 2325 (12.3%). In adjusted analysis, Black patient (versus White patient adjusted odds ratio, 0.65 [95% CI, 0.57-0.73]; <i>P</i><0.001) and Hispanic patient admissions (versus White adjusted odds ratio, 0.78 [95% CI, 0.66-0.92]; <i>P</i>=0.003) were less likely to receive SRT. Among admissions undergoing SRT, in-hospital mortality was significantly higher for Hispanic (adjusted odds ratio, 3.38 [95% CI, 1.81-6.30], <i>P</i><0.001) and other racial and ethnic groups (adjusted odds ratio 2.02 [95% CI, 1.00-4.11]; <i>P</i>=0.05) compared with White patient admissions, whereas Black patient admissions had comparable mortality. Black, Hispanic, and other ethnic group patients had higher rates of SRT complications and more frequent dismissals to acute care facilities. <br /><b>Conclusions:</b><br/>Among obstructive hypertrophic cardiomyopathy hospitalizations, minoritized racial groups were less likely to receive SRT. Importantly, hospitalizations of Hispanic and other ethnic patients undergoing SRT had significantly higher in-hospital mortality and complication rates. Further studies with granular echocardiographic information to assess indications for SRT are needed to better understand these differences.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e026661; epub ahead of print</small></div>
Patlolla SH, Schaff HV, Nishimura RA, Eleid MF, Geske JB, Ommen SR
J Am Heart Assoc: 24 Dec 2022:e026661; epub ahead of print | PMID: 36565202
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<div><h4>Cardiovascular Risk Factors and Risk of Alzheimer Disease and Mortality: A Latent Class Approach.</h4><i>Ruthirakuhan M, Cogo-Moreira H, Swardfager W, Herrmann N, Lanctot KL, Black SE</i><br /><AbstractText><br /><b>Background:</b><br/>Cardiovascular risk factors co-occur with one another, and little is known about the extent of their clustering and risk of Alzheimer disease (AD). We identify groups of cardiovascular risk factors in cognitively normal individuals and investigate between-group differences in incident AD and death. Methods and Results Cognitively normal individuals were recruited from the National Alzheimer\'s Coordinator Center. A latent class analysis was conducted with hypertension, hypercholesterolemia, heart condition, stroke, smoking history, diabetes, and high body mass index. Between-group differences in the incidence of AD, mortality, and mortality-adjusted AD were investigated. This study included 12 412 cognitively normal individuals (average follow-up, 65 months). Three groups were identified: (1) low probabilities of cardiovascular risk factors (reference; N=5398 [43%]), (2) hypertension and hypercholesterolemia (vascular-dominant; N=5721 [46%]), and (3) hypertension, hypercholesterolemia, diabetes, and high body mass index (vascular-metabolic; N=1293 [10%]). Both vascular groups were significantly older, had more men, were slightly less educated, and were slightly more cognitively impaired than the reference group (all <i>P</i><0.05). However, only the vascular-metabolic group had a significantly younger age of death compared with the reference group (84.3 versus 88.7 years, <i>P</i><0.001). Only the vascular-dominant group had a greater incidence of AD (odds ratio [OR], 1.30; <i>P</i><0.001) compared with the reference group. Mortality was greater in the vascular-dominant (OR, 3.26; <i>P</i><0.001) and vascular-metabolic groups (OR, 1.84; <i>P</i>=0.02). Mortality-adjusted AD was greater in the vascular-dominant (OR, 1.54; <i>P</i>=0.02) and vascular-metabolic groups (OR, 1.46; <i>P</i>=0.04). <br /><b>Conclusions:</b><br/>Three distinct cardiovascular risk factor groups were identified in cognitively normal elderly individuals. Only the vascular-dominant group was associated with a greater incidence of AD. Selective mortality may contribute to the attenuated association between the vascular-metabolic group and incident AD.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e025724; epub ahead of print</small></div>
Ruthirakuhan M, Cogo-Moreira H, Swardfager W, Herrmann N, Lanctot KL, Black SE
J Am Heart Assoc: 24 Dec 2022:e025724; epub ahead of print | PMID: 36565204
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<div><h4>Disparate Cardiovascular Hospitalization Trends Among Young and Middle-Aged Adults Within and Across Race and Ethnicity Groups in Four States in the United States.</h4><i>Akhabue E, Rua M, Gandhi P, Kim JH, Cantor JC, Setoguchi S</i><br /><AbstractText><br /><b>Background:</b><br/>Inpatient hospitalizations for cardiovascular disease (CVD) decreased nationally in the past decade. However, data are lacking on whether national declines represent trends within and across race and ethnicity populations from different US regions. Methods and Results Using State Inpatient Databases, Census Bureau and Behavioral Risk Factor Surveillance System data for Florida, Kentucky, New Jersey, and North Carolina, we identified all CVD hospitalizations and population characteristics for adults aged 18 to 64 years between January 1, 2009 and December 31, 2018. We calculated yearly CVD hospitalization rates for each state for the overall population, by sex, race, and ethnicity. We modeled yearly trends in age-adjusted CVD hospitalization rate in each state using negative binomial regression. State base populations were similar by age (mean age: 40-42 years) and sex (50%-51% female) throughout the study period. There were 314 973 and 288 843 total CVD hospitalizations among the 4 states in 2009 and 2018, respectively. Crude hospitalization rates declined in all states (age 18-44 years NJ: -33.4%; KY: -17.0%; FL: -11.9%; NC: -11.2%; age 45-64 years NJ: -29.8%; KY: -20.3%; FL: -12.2%; NC: -11.6%) over the study period. In age-adjusted models, overall hospitalization rates declined significantly in NJ -2.5%/y (95% CI, -2.9 to -2.1) and in KY -1.6%/y (-1.9 to -1.2) with no significant declining trend in FL and NC. Similar findings were present by sex. Among non-Hispanic White populations, mean yearly decline in hospitalization rate was significant in all states except FL, with the greatest declines in NJ (-3.8%/y [-4.4 to -3.2], <i>P</i> values for state-year interaction <0.0001). By contrast, a significant declining trend was present for non-Hispanic Black and Hispanic populations only in NJ (<i>P</i> values for state-year interaction <0.001). We found similar differences in trend between states in sensitivity analyses incorporating additional demographic and comorbid characteristics. <br /><b>Conclusions:</b><br/>Decreases in CVD hospitalization rates in the past decade among nonelderly adults varied considerably by state and appeared largely driven by declines among non-Hispanic White populations. Overall declines did not represent divergent trends between states within non-Hispanic Black and Hispanic populations. Recognition of differences not just between but also within race and ethnicity populations should inform national and local policy initiatives aimed at reducing disparities in CVD outcomes.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e7978; epub ahead of print</small></div>
Akhabue E, Rua M, Gandhi P, Kim JH, Cantor JC, Setoguchi S
J Am Heart Assoc: 24 Dec 2022:e7978; epub ahead of print | PMID: 36565205
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<div><h4>Occult Diastolic Dysfunction and Adverse Clinical Outcomes in Adolescents and Young Adults With Fontan Circulation.</h4><i>Peck D, Averin K, Khoury P, Veldhuis G, ... Veldtman G, Goldstein BH</i><br /><AbstractText><br /><b>Background:</b><br/>In Fontan circulation, diastolic dysfunction portends a worse clinical outcome but may be concealed during routine assessment. Invasive evaluation with rapid volume expansion (RVE) can identify patients with occult diastolic dysfunction (ODD). We sought to evaluate the association between ODD and adverse clinical outcomes at medium-term follow-up. Methods and Results We conducted a single-center observational study of patients with Fontan circulation who underwent clinical catheterization with RVE from 2012 to 2017. ODD was defined as post-RVE end-diastolic pressure ≥15 mm Hg. A composite adverse clinical outcome included mortality, cardiac transplant, ventricular assist device, plastic bronchitis, protein-losing enteropathy, arrhythmia, stroke/thrombus, or cardiac-related hospital admission. Proportional hazards regression was used to compare the ODD-positive and ODD-negative groups for risk of the composite adverse clinical outcome. Eighty-nine patients with Fontan circulation (47% female patients) were included at a median age of 14 years. ODD was identified in 31%. Fontan duration was longer in the ODD group (<i>P</i>=0.001). The composite adverse clinical outcome occurred more frequently in the ODD group (52 versus 26%, <i>P</i>=0.03) during a median follow-up duration of 2.9 years after catheterization. ODD (hazard ratio [HR], 2.68 [95% CI, 1.28-5.66]; <i>P</i>=0.02) and Fontan duration (HR, 1.07 [95% CI, 1.02-1.12]; <i>P</i>=0.003) were associated with the composite adverse clinical outcome. When stratified by Fontan duration, ODD remained significantly associated with the hazard of adverse clinical outcomes in patients with a Fontan duration ≥10 years (HR, 2.57 [95% CI, 1.03-6.57]; <i>P</i>=0.04). <br /><b>Conclusions:</b><br/>Cardiac catheterization with rapid volume expansion reveals a significant incidence of ODD, which relates to Fontan duration. ODD is associated with an increased hazard of adverse clinical outcomes during medium-term follow-up, especially in patients with longer Fontan duration. ODD may portend a worse prognosis in Fontan circulation.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e026508; epub ahead of print</small></div>
Peck D, Averin K, Khoury P, Veldhuis G, ... Veldtman G, Goldstein BH
J Am Heart Assoc: 24 Dec 2022:e026508; epub ahead of print | PMID: 36565206
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<div><h4>Lipid-Lowering Trials Are Not Representative of Patients Managed in Clinical Practice: A Systematic Review and Meta-Analysis of Exclusion Criteria.</h4><i>Aeschbacher-Germann M, Kaiser N, Speierer A, Blum MR, ... Rodondi N, Moutzouri E</i><br /><AbstractText><br /><b>Background:</b><br/>Randomized clinical trials (RCTs) might not be representative of the real-world population because of unreasonable exclusion criteria. We sought to determine which groups of patients are excluded from RCTs that included lipid-lowering therapy. Methods and Results We retrieved all trials from the Cholesterol Treatment Trialists Collaboration and systematically searched for large (≥1000 participants) lipid-lowering therapy RCTs, defined as statins, ezetimibe, and PCSK9 inhibitors. We predefined groups: older adults (>70 or >75 years), women, non-Whites, chronic kidney failure, heart failure, immunosuppression, cancer, dementia, treated thyroid disease, chronic obstructive pulmonary disease, mental illness, atrial fibrillation, multimorbidity (≥2 chronic diseases), and polypharmacy. We counted the number of RCTs excluding patients of the predefined groups and meta-analyzed the prevalence of included patients to obtain pooled estimates with a random-effects model. We included 42 RCTs (298 605 patients). Eighty-one percent of trials excluded patients with severe and 76% those with moderate kidney failure. Seventy-one percent of trials excluded groups of women, 64% excluded patients with moderate to severe heart failure, 64% those with immunosuppressant conditions, 48% those with cancer, 29% those with dementia, and 29% of trials excluded older adults. The pooled prevalence for patients >70 years of age was 25% (95% CI, 0%-49%), 11% (3%-18%) for >75 years of age, and 51% (38%-63%) for multimorbidity. <br /><b>Conclusions:</b><br/>The majority of lipid-lowering therapy trials excluded patients with common diseases, such as moderate-to-severe kidney disease or heart failure or with immunosuppression. Underrepresenting certain populations, including women and older adults, might lead to limited transportability of study results and uncertainty on possible side-effects and efficacy in these groups. Future trials should promote diversity in the recruitment strategies and improve equity in cardiovascular research. Registration URL: ClinicalTrials.gov; Unique Identifier: CRD42021253909.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e026551; epub ahead of print</small></div>
Aeschbacher-Germann M, Kaiser N, Speierer A, Blum MR, ... Rodondi N, Moutzouri E
J Am Heart Assoc: 24 Dec 2022:e026551; epub ahead of print | PMID: 36565207
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<div><h4>Association of Incidentally Discovered Covert Cerebrovascular Disease Identified Using Natural Language Processing and Future Dementia.</h4><i>Kent DM, Leung LY, Zhou Y, Luetmer PH, ... Liu H, Chen W</i><br /><AbstractText><br /><b>Background:</b><br/>Covert cerebrovascular disease (CCD) has been shown to be associated with dementia in population-based studies with magnetic resonance imaging (MRI) screening, but dementia risk associated with incidentally discovered CCD is not known. Methods and Results Individuals aged ≥50 years enrolled in the Kaiser Permanente Southern California health system receiving head computed tomography (CT) or MRI for nonstroke indications from 2009 to 2019, without prior ischemic stroke/transient ischemic attack, dementia/Alzheimer disease, or visit reason/scan indication suggestive of cognitive decline or stroke were included. Natural language processing identified incidentally discovered covert brain infarction (id-CBI) and white matter disease (id-WMD) on the neuroimage report; white matter disease was characterized as mild, moderate, severe, or undetermined. We estimated risk of dementia associated with id-CBI and id-WMD. Among 241 050 qualified individuals, natural language processing identified 69 931 (29.0%) with id-WMD and 11 328 (4.7%) with id-CBI. Dementia incidence rates (per 1000 person-years) were 23.5 (95% CI, 22.9-24.0) for patients with id-WMD, 29.4 (95% CI, 27.9-31.0) with id-CBI, and 6.0 (95% CI, 5.8-6.2) without id-CCD. The association of id-WMD with future dementia was stronger in younger (aged <70 years) versus older (aged ≥70 years) patients and for CT- versus MRI-discovered lesions. For patients with versus without id-WMD on CT, the adjusted HR was 2.87 (95% CI, 2.58-3.19) for older and 1.87 (95% CI, 1.79-1.95) for younger patients. For patients with versus without id-WMD on MRI, the adjusted HR for dementia risk was 2.28 (95% CI, 1.99-2.62) for older and 1.48 (95% CI, 1.32-1.66) for younger patients. The adjusted HR for id-CBI was 2.02 (95% CI, 1.70-2.41) for older and 1.22 (95% CI, 1.15-1.30) for younger patients for either modality. Dementia risk was strongly correlated with id-WMD severity; adjusted HRs compared with patients who were negative for id-WMD by MRI ranged from 1.41 (95% CI, 1.25-1.60) for those with mild disease on MRI to 4.11 (95% CI, 3.58-4.72) for those with severe disease on CT. <br /><b>Conclusions:</b><br/>Incidentally discovered CCD is common and associated with a high risk of dementia, representing an opportunity for prevention. The association is strengthened when discovered at younger age, by increasing id-WMD severity, and when id-WMD is detected by CT scan rather than MRI.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 24 Dec 2022:e027672; epub ahead of print</small></div>
Kent DM, Leung LY, Zhou Y, Luetmer PH, ... Liu H, Chen W
J Am Heart Assoc: 24 Dec 2022:e027672; epub ahead of print | PMID: 36565208
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<div><h4>Coffee and Green Tea Consumption and Cardiovascular Disease Mortality Among People With and Without Hypertension.</h4><i>Teramoto M, Yamagishi K, Muraki I, Tamakoshi A, Iso H</i><br /><AbstractText><br /><b>Background:</b><br/>This study was conducted to examine the impacts of coffee and green tea consumption on cardiovascular disease (CVD) mortality among people with severe hypertension. Methods and Results In the JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk), 18 609 participants (6574 men and 12 035 women) aged 40 to 79 years at baseline who completed a lifestyle, diet, and medical history questionnaire, and health examinations, were followed up until 2009. We classified the participants into four blood pressure (BP) categories: optimal and normal BP, high-normal BP, grade 1 hypertension, and grade 2-3 hypertension. A Cox proportional hazard model was used to calculate the multivariable hazard ratios with 95% CIs of CVD mortality. During the 18.9 years of median follow-up, a total of 842 CVD deaths were documented. Coffee consumption was associated with an increased risk of CVD mortality among people with grade 2-3 hypertension; the multivariable hazard ratios (95% CI) of CVD mortality were 0.98 (0.67-1.43) for <1 cup/day, 0.74 (0.37-1.46) for 1 cup/day, and 2.05 (1.17-3.59) for ≥2 cups/day, compared with non-coffee drinkers. Such associations were not found among people with optimal and normal, high-normal BP, and grade 1 hypertension. Green tea consumption was not associated with an increased risk of CVD across any BP categories. <br /><b>Conclusions:</b><br/>Heavy coffee consumption was associated with an increased risk of CVD mortality among people with severe hypertension, but not people without hypertension and with grade 1 hypertension. In contrast, green tea consumption was not associated with an increased risk of CVD mortality across all categories of BP.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 21 Dec 2022:e026477; epub ahead of print</small></div>
Teramoto M, Yamagishi K, Muraki I, Tamakoshi A, Iso H
J Am Heart Assoc: 21 Dec 2022:e026477; epub ahead of print | PMID: 36542728
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<div><h4>Emergency Medical Services Stroke Care Performance Variability in Michigan: Analysis of a Statewide Linked Stroke Registry.</h4><i>Oostema JA, Nickles A, Luo Z, Reeves MJ</i><br /><AbstractText><br /><b>Background:</b><br/>Emergency medical services (EMS) compliance with recommended prehospital care for patients with acute stroke is inconsistent; however, sources of variability in compliance are not well understood. The current analysis utilizes a linkage between a statewide stroke registry and EMS information system data to explore patient and EMS agency-level contributions to variability in prehospital care. Methods and Results This is a retrospective analysis of a cohort of confirmed stroke cases transported by EMS to hospitals participating in a statewide stroke registry. Using EMS information system data, the authors quantified EMS compliance with 6 performance measures derived from national guidelines for prehospital stroke care: prehospital stroke scale performance, glucose check, stroke recognition, on-scene time ≤15 minutes, time last known well documentation, and hospital prenotification. Multilevel multivariable logistic regression analysis was then used to examine associations between patient-level demographic and clinical characteristics and EMS compliance while accounting for and quantifying the variation attributable to agency of transport and recipient hospital. Over an 18-month period, EMS and stroke registry records were linked for 5707 EMS-transported stroke cases. Compliance ranged from 24% of cases for last known well documentation to 82% for documentation of a glucose check. The other measures were documented in approximately half of cases. Older age, higher National Institutes of Health Stroke Scale, and earlier presentation were associated with more compliant prehospital care. EMS agencies accounted for more than half of the variation in EMS prehospital stroke scale documentation and last known well documentation and 27% of variation in glucose check but <10% of stroke recognition and prenotification variability. <br /><b>Conclusions:</b><br/>EMS stroke care remains highly variable across different performance measures and EMS agencies. EMS agency and electronic medical record type are important sources of variability in compliance with key prehospital performance metrics for stroke.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 20 Dec 2022:e026834; epub ahead of print</small></div>
Oostema JA, Nickles A, Luo Z, Reeves MJ
J Am Heart Assoc: 20 Dec 2022:e026834; epub ahead of print | PMID: 36537345
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Abstract
<div><h4>Interleukin-29 Accelerates Vascular Calcification via JAK2/STAT3/BMP2 Signaling.</h4><i>Hao N, Zhou Z, Zhang F, Li Y, ... Li C, Wang F</i><br /><AbstractText><br /><b>Background:</b><br/>Vascular calcification (VC), associated with enhanced cardiovascular morbidity and mortality, is characterized by the osteogenic transdifferentiation of vascular smooth muscle cells. Inflammation promotes VC initiation and progression. Interleukin (IL)-29, a newly discovered member of type III interferon, has recently been implicated in the pathogenesis of autoimmune diseases. Here we evaluated the role of IL-29 in the VC process and underlying inflammatory mechanisms. Methods and Results The mRNA expression of IL-29 was significantly increased and positively associated with an increase in BMP2 (bone morphogenetic protein 2) mRNA level in calcified carotid arteries from patients with coronary artery disease or chronic kidney disease. IL-29 and BMP2 proteins are colocalized in human calcified arteries. IL-29 binding to its specific receptor IL-28Rα (IL-28 receptor α) (IL-29/IL-28Rα) inhibited the proliferation of rat vascular smooth muscle cells without altering cell apoptosis or migration. IL-29 promoted the calcification of rat vascular smooth muscle cells and their osteogenic transdifferentiation in vitro as well as the rat aortic ring calcification ex vivo, induced by the calcification medium or osteogenic medium. The procalcification effect of IL-29 was reduced by pharmacological inhibition of IL-29/IL-28Rα binding as well as suppression of janus kinase 2/signal transducer and activator of transcription pathway activation, accompanied by decreased BMP2 expression in the cultured rat vascular smooth muscle cells. <br /><b>Conclusions:</b><br/>These results suggest an important role of IL-29 in VC development, at least partly, via activating the janus kinase 2/signal transducer and activator of transcription 3 signaling. Inhibition of IL-29 or its specific receptor, IL-28Rα, may provide a novel strategy to reduce VC in patients with vascular diseases.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 20 Dec 2022:e027222; epub ahead of print</small></div>
Hao N, Zhou Z, Zhang F, Li Y, ... Li C, Wang F
J Am Heart Assoc: 20 Dec 2022:e027222; epub ahead of print | PMID: 36537334
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Abstract
<div><h4>PVECs-Derived Exosomal microRNAs Regulate PASMCs via FoxM1 Signaling in IUGR-induced Pulmonary Hypertension.</h4><i>Luo X, Hang C, Zhang Z, Le K, ... Zhong Y, Du L</i><br /><AbstractText><br /><b>Background:</b><br/>Intrauterine growth restriction (IUGR) is closely related to systemic or pulmonary hypertension (PH) in adulthood. Aberrant crosstalk between pulmonary vascular endothelial cells (PVECs) and pulmonary arterial smooth muscle cells (PASMCs) that is mediated by exosomes plays an essential role in the progression of PH. FoxM1 (Forkhead box M1) is a key transcription factor that governs many important biological processes. Methods and Results IUGR-induced PH rat models were established. Transwell plates were used to coculture PVECs and PASMCs. Exosomes were isolated from PVEC-derived medium, and a microRNA (miRNA) screening was proceeded to identify effects of IUGR on small RNAs enclosed within exosomes. Dual-Luciferase assay was performed to validate the predicted binding sites of miRNAs on FoxM1 3\' untranslated region. FoxM1 inhibitor thiostrepton was used in IUGR-induced PH rats. In this study, we found that FoxM1 expression was remarkably increased in IUGR-induced PH, and PASMCs were regulated by PVECs through FoxM1 signaling in a non-contact way. An miRNA screening showed that miR-214-3p, miR-326-3p, and miR-125b-2-3p were downregulated in PVEC-derived exosomes of the IUGR group, which were associated with overexpression of FoxM1 and more significant proliferation and migration of PASMCs. Dual-Luciferase assay demonstrated that the 3 miRNAs directly targeted FoxM1 3\' untranslated region. FoxM1 inhibition blocked the PVECs-PASMCs crosstalk and reversed the abnormal functions of PASMCs. In vivo, treatment with thiostrepton significantly reduced the severity of PH. <br /><b>Conclusions:</b><br/>Transmission of exosomal miRNAs from PVECs regulated the functions of PASMCs via FoxM1 signaling, and FoxM1 may serve as a potential therapeutic target in IUGR-induced PH.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 19 Dec 2022:e027177; epub ahead of print</small></div>
Luo X, Hang C, Zhang Z, Le K, ... Zhong Y, Du L
J Am Heart Assoc: 19 Dec 2022:e027177; epub ahead of print | PMID: 36533591
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<div><h4>Predictors of Adverse Prognosis in Patients With Acute Coronary Syndrome Caused by Plaque Erosion With a Nonstent Strategy.</h4><i>Yin Y, Lei F, Fang C, Jiang S, ... Dai J, Yu B</i><br /><AbstractText><br /><b>Background:</b><br/>The EROSION (Effective Anti-Thrombotic Therapy Without Stenting: Intravascular Optical Coherence Tomography-Based Management in Plaque Erosion) study demonstrated that antithrombotic therapy without stenting was safe and feasible in selected patients with acute coronary syndrome caused by plaque erosion. However, the factors related to the prognosis of these patients are not clear. This study aimed to explore the predictors of an adverse prognosis of a nonstent strategy in a larger sample size. Methods and Results A total of 252 (55 patients were from the EROSION study) patients with acute coronary syndrome with plaque erosion who met the inclusion criteria of the EROSION study and completed clinical follow-up were enrolled. Patients were divided into 2 groups according to the occurrence of major adverse cardiovascular events (MACE), which were defined as the composite of cardiac death, recurrent myocardial infarction, ischemia-driven target lesion revascularization, rehospitalization because of unstable or progressive angina, major bleeding, and stroke. Among 232 patients with acute coronary syndrome included in the final analysis, 50 patients (21.6%) developed MACE at a median follow-up of 2.9 years. Compared with patients without MACE, patients with MACE were older and had a higher degree of percentage of area stenosis (72.2%±9.4% versus 64.2%±15.7%, <i>P</i><0.001) and thrombus burden (24.4%±10.4% versus 20.4%±10.9%, <i>P</i>=0.010) at baseline. Multivariate Cox regression analysis confirmed that age, percentage of area stenosis, and thrombus burden were predictors of MACE. The best cutoff values of predictors were age ≥60 years, percentage of area stenosis ≥63.5%, and thrombus burden ≥18.5%, respectively, and when they were all present, the rate of MACE rose to 57.7%. <br /><b>Conclusions:</b><br/>The nonstent treatment strategy of patients with acute coronary syndrome caused by plaque erosion was heterogeneous, and patients aged ≥60 years, percentage of area stenosis ≥63.5%, and thrombus burden ≥18.5% may predict a worse clinical outcome.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 19 Dec 2022:e026414; epub ahead of print</small></div>
Yin Y, Lei F, Fang C, Jiang S, ... Dai J, Yu B
J Am Heart Assoc: 19 Dec 2022:e026414; epub ahead of print | PMID: 36533592
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<div><h4>Depression and Anxiety Are Associated With Cardiovascular Health in Young Adults.</h4><i>Patterson SL, Marcus M, Goetz M, Vaccarino V, Gooding HC</i><br /><AbstractText><br /><b>Background:</b><br/>Cardiovascular health (CVH) declines in young adulthood, and mood disorders commonly emerge during this life stage. This study examined the association between depression, anxiety, and CVH metrics among young adults. Methods and Results We conducted a cross-sectional analysis of participants aged 18 to 34 years who completed the Emory Healthy Aging Study Health History Questionnaire (n=875). We classified participants as having poor, intermediate, or ideal levels of the 8 CVH metrics using definitions set forth by the American Heart Association with adaptions when necessary. We defined depression and anxiety as absent, mild, or moderate to severe using standard cutoffs for Patient Health Questionnaire and General Anxiety Disorder scales. We used multivariable regression to examine the association between depression and anxiety and CVH, adjusting for age, sex, race and ethnicity, income, and education. The mean participant age was 28.3 years, and the majority identified as women (724; 82.7%); 129 (14.7%) participants had moderate to severe anxiety, and 128 (14.6%) participants had moderate to severe depression. Compared with those without anxiety, participants with moderate to severe anxiety were less likely to meet ideal levels of physical activity (adjusted prevalence ratio [aPR], 0.60 [95% CI, 0.44-0.82]), smoking (aPR, 0.90 [95% CI, 0.82-0.99]), and body mass index (aPR, 0.79 [95% CI, 0.66-0.95]). Participants with moderate to severe depression were less likely than those without depression to meet ideal levels of physical activity (aPR, 0.48 [95% CI, 0.34-0.69]), body mass index (aPR, 0.75 [95% CI, 0.61-0.91]), sleep (aPR, 0.79 [95% CI, 0.66-0.94]), and blood pressure (aPR, 0.92 [95% CI, 0.86-0.99]). <br /><b>Conclusions:</b><br/>Anxiety and depression are associated with less ideal CVH in young adults. Interventions targeting CVH behaviors such as physical activity, diet, and sleep may improve both mood and CVH.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 19 Dec 2022:e027610; epub ahead of print</small></div>
Patterson SL, Marcus M, Goetz M, Vaccarino V, Gooding HC
J Am Heart Assoc: 19 Dec 2022:e027610; epub ahead of print | PMID: 36533593
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