Journal: J Am Heart Assoc

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Abstract

Estimated Yield of Screening for Heterozygous Familial Hypercholesterolemia With and Without Genetic Testing in US Adults.

Bellows BK, Khera AV, Zhang Y, Ruiz-Negrón N, ... de Ferranti SD, Moran AE

Background:
Heterozygous familial hypercholesterolemia (FH) is a common genetic disorder causing premature cardiovascular disease. Despite this, there is no national screening program in the United States to identify individuals with FH or likely pathogenic FH genetic variants. Methods and Results The clinical characteristics and FH variant status of 49 738 UK Biobank participants were used to develop a regression model to predict the probability of having any FH variants. The regression model and modified Dutch Lipid Clinic Network criteria were applied to 39 790 adult participants (aged ≥20 years) in the National Health and Nutrition Examination Survey to estimate the yield of FH screening programs using Dutch Lipid Clinic Network clinical criteria alone (excluding genetic variant status), genetic testing alone, or combining clinical criteria with genetic testing. The regression model accurately predicted FH variant status in UK Biobank participants (observed prevalence, 0.27%; predicted, 0.26%; area under the receiver-operator characteristic curve, 0.88). In the National Health and Nutrition Examination Survey, the estimated yield per 1000 individuals screened (95% CI) was 3.7 (3.0-4.6) FH cases with the Dutch Lipid Clinic Network clinical criteria alone, 3.8 (2.7-5.1) cases with genetic testing alone, and 6.6 (5.3-8.0) cases by combining clinical criteria with genetic testing. In young adults aged 20 to 39 years, using clinical criteria alone was estimated to yield 1.3 (95% CI, 0.6-2.5) FH cases per 1000 individuals screened, which was estimated to increase to 4.2 (95% CI, 2.6-6.4) FH cases when combining clinical criteria with genetic testing.
Conclusions:
Screening for FH using a combination of clinical criteria with genetic testing may increase identification and the opportunity for early treatment of individuals with FH.




J Am Heart Assoc: 18 May 2022:e025192; epub ahead of print
Bellows BK, Khera AV, Zhang Y, Ruiz-Negrón N, ... de Ferranti SD, Moran AE
J Am Heart Assoc: 18 May 2022:e025192; epub ahead of print | PMID: 35583136
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Abstract

Temporal Trends in Adverse Pregnancy Outcomes in Birthing Individuals Aged 15 to 44 Years in the United States, 2007 to 2019.

Freaney PM, Harrington K, Molsberry R, Perak AM, ... Lloyd-Jones DM, Khan SS

Background:
Adverse pregnancy outcomes (APOs) (hypertensive disorders of pregnancy [HDP], preterm delivery [PTD], or low birth weight [LBW]) are associated adverse maternal and offspring cardiovascular outcomes. Therefore, we sought to describe nationwide temporal trends in the burden of each APO (HDP, PTD, LBW) from 2007 to 2019 to inform strategies to optimize maternal and offspring health outcomes. Methods and Results We performed a serial cross-sectional analysis of APO subtypes (HDP, PTD, LBW) from 2007 to 2019. We included maternal data from all live births that occurred in the United States using the National Center for Health Statistics Natality Files. We quantified age-standardized and age-specific rates of APOs per 1000 live births and their respective mean annual percentage change. All analyses were stratified by self-report of maternal race and ethnicity. Among 51 685 525 live births included, 15% were to non-Hispanic Black individuals, 24% Hispanic individuals, and 6% Asian individuals. Between 2007 and 2019, age standardized HDP rates approximately doubled, from 38.4 (38.2-38.6) to 77.8 (77.5-78.1) per 1000 live births. A significant inflection point was observed in 2014, with an acceleration in the rate of increase of HDP from 2007 to 2014 (+4.1% per year [3.6-4.7]) to 2014 to 2019 (+9.1% per year [8.1-10.1]). Rates of PTD and LBW increased significantly when co-occurring in the same pregnancy with HDP. Absolute rates of APOs were higher in non-Hispanic Black individuals and in older age groups. However, similar relative increases were seen across all age,racial and ethnic groups.
Conclusions:
In aggregate, APOs now complicate nearly 1 in 5 live births. Incidence of HDP has increased significantly between 2007 and 2019 and contributed to the reversal of favorable trends in PTD and LBW. Similar patterns were observed in all age groups, suggesting that increasing maternal age at pregnancy does not account for these trends. Black-White disparities persisted throughout the study period.




J Am Heart Assoc: 18 May 2022:e025050; epub ahead of print
Freaney PM, Harrington K, Molsberry R, Perak AM, ... Lloyd-Jones DM, Khan SS
J Am Heart Assoc: 18 May 2022:e025050; epub ahead of print | PMID: 35583146
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Abstract

Bidirectional Association Between Kidney Function and Atrial Fibrillation: A Population-Based Cohort Study.

van der Burgh AC, Geurts S, Ikram MA, Hoorn EJ, Kavousi M, Chaker L

Background:
Consensus lacks concerning a bidirectional association between kidney function and atrial fibrillation (AF), but this is crucial information for prevention/treatment efforts for both chronic kidney disease and AF. Therefore, we investigated the bidirectional association between kidney function and AF. Methods and Results This study was a prospective cohort study including 9228 participants (mean age, 64.9 years; 57.2% women) with information on kidney function (estimated glomerular filtration rate [eGFR] based on serum creatinine [eGFRcreat], cystatin C [eGFRcys], or both [eGFRcreat-cys], and urine albumin-to-creatinine ratio) and AF. Reduced kidney function was defined as eGFRcreat <60 mL/min per 1.73 m2. Cox proportional-hazards, logistic regression, linear mixed, and joint models were used to investigate the association of kidney function with AF and vice versa. During follow-up (median of 8.0 years), 780 events of incident AF occurred. Lower eGFRcys and eGFRcreat-cys were associated with increased AF risk (hazard ratio [HR], 1.08 [95% CI, 1.03-1.14] and HR, 1.07 [95% CI, 1.01-1.14], respectively, per 10 mL/min per 1.73 m2 eGFR decrease). For eGFRcys and eGFRcreat-cys, 10-year cumulative incidence of AF was 16% (eGFR <60) and 6% (eGFR ≥60). Prevalent AF (versus no prevalent AF) was associated with 2.85 mL/min per 1.73 m2 lower eGFRcreat and with a faster decline of eGFRcreat with age. Prevalent AF was associated with a 1.3-fold increased risk of incident reduced kidney function.
Conclusions:
Kidney function, especially eGFRcys, and AF are bidirectionally associated. There are currently no targeted prevention efforts for AF in patients with mild chronic kidney disease and vice versa. Our results could provide the first step to improve prediction/prevention of both conditions.




J Am Heart Assoc: 17 May 2022; 11:e025303
van der Burgh AC, Geurts S, Ikram MA, Hoorn EJ, Kavousi M, Chaker L
J Am Heart Assoc: 17 May 2022; 11:e025303 | PMID: 35579615
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Abstract

Stroke Risk Stratification in Patients With Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting.

Taha A, Nielsen SJ, Franzén S, Rezk M, ... Jeppsson A, Bergfeldt L

Background:
The CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke or TIA [transient ischemic attack], vascular disease, age 65 to 74 years, sex category female; 2 indicates 2 points, otherwise 1 point) scoring system is recommended to guide decisions on oral anticoagulation therapy for stroke prevention in patients with nonsurgery atrial fibrillation. A score ≥1 in men and ≥2 in women, corresponding to an annual stroke risk exceeding 1%, warrants long-term oral anticoagulation provided the bleeding risk is acceptable. However, in patients with new-onset postoperative atrial fibrillation, the optimal risk stratification method is unknown. The aim of this study was therefore to evaluate the CHA2DS2-VASc scoring system for estimating the 1-year ischemic stroke risk in patients with new-onset postoperative atrial fibrillation after coronary artery bypass grafting. Methods and Results All patients with new-onset postoperative atrial fibrillation and without oral anticoagulation after first-time isolated coronary artery bypass grafting performed in Sweden during 2007 to 2017 were eligible for this registry-based observational cohort study. The 1-year ischemic stroke rate at each step of the CHA2DS2-VASc score was estimated using a Kaplan-Meier estimator. Of the 6368 patients included (mean age, 69.9 years; 81% men), >97% were treated with antiplatelet drugs. There were 147 ischemic strokes during the first year of follow-up. The ischemic stroke rate at 1 year was 0.3%, 0.7%, and 1.5% in patients with CHA2DS2-VASc scores of 1, 2, and 3, respectively, and ≥2.3% in patients with a score ≥4. A sensitivity analysis, with the inclusion of patients on anticoagulants, was performed and supported the primary results.
Conclusions:
Patients with new-onset atrial fibrillation after coronary artery bypass grafting and a CHA2DS2-VASc score <3 have such a low 1-year risk for ischemic stroke that oral anticoagulation therapy should probably be avoided.




J Am Heart Assoc: 16 May 2022:e024703; epub ahead of print
Taha A, Nielsen SJ, Franzén S, Rezk M, ... Jeppsson A, Bergfeldt L
J Am Heart Assoc: 16 May 2022:e024703; epub ahead of print | PMID: 35574947
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Abstract

Gradual Versus Abrupt Reperfusion During Primary Percutaneous Coronary Interventions in ST-Segment-Elevation Myocardial Infarction (GUARD).

Sezer M, Escaned J, Broyd CJ, Umman B, ... van Royen N, Umman S

Background:
Intramyocardial edema and hemorrhage are key pathological mechanisms in the development of reperfusion-related microvascular damage in ST-segment-elevation myocardial infarction. These processes may be facilitated by abrupt restoration of intracoronary pressure and flow triggered by primary percutaneous coronary intervention. We investigated whether pressure-controlled reperfusion via gradual reopening of the infarct-related artery may limit microvascular injury in patients undergoing primary percutaneous coronary intervention. Methods and Results A total of 83 patients with ST-segment-elevation myocardial infarction were assessed for eligibility and 53 who did not meet inclusion criteria were excluded. The remaining 30 patients with totally occluded infarct-related artery were randomized to the pressure-controlled reperfusion with delayed stenting (PCRDS) group (n=15) or standard primary percutaneous coronary intervention with immediate stenting (IS) group (n=15) (intention-to-treat population). Data from 5 patients in each arm were unsuitable to be included in the final analysis. Finally, 20 patients undergoing primary percutaneous coronary intervention who were randomly assigned to either IS (n=10) or PCRDS (n=10) were included. In the PCRDS arm, a 1.5-mm balloon was used to achieve initial reperfusion with thrombolysis in myocardial infarction grade 3 flow and, subsequently, to control distal intracoronary pressure over a 30-minute monitoring period (MP) until stenting was performed. In both study groups, continuous assessment of coronary hemodynamics with intracoronary pressure and Doppler flow velocity was performed, with a final measurement of zero flow pressure (primary end point of the study) at the end of a 60-minute MP. There were no complications associated with IS or PCRDS. PCRDS effectively led to lower distal intracoronary pressures than IS over 30 minutes after reperfusion (71.2±9.37 mm Hg versus 90.13±12.09 mm Hg, P=0.001). Significant differences were noted between study arms in the microcirculatory response over MP. Microvascular perfusion progressively deteriorated in the IS group and at the end of MP, and hyperemic microvascular resistance was significantly higher in the IS arm as compared with the PCDRS arm (2.83±0.56 mm Hg.s.cm-1 versus 1.83±0.53 mm Hg.s.cm-1, P=0.001). The primary end point (zero flow pressure) was significantly lower in the PCRDS group than in the IS group (41.46±17.85 mm Hg versus 76.87±21.34 mm Hg, P=0.001). In the whole study group (n=20), reperfusion pressures measured at predefined stages in the early reperfusion period showed robust associations with zero flow pressure values measured at the end of the 1-hour MP (immediately after reperfusion: r=0.782, P<0.001; at the 10th minute: r=0.796, P<0.001; and at the 20th minute: r=0.702, P=0.001) and peak creatine kinase MB level (immediately after reperfusion: r=0.653, P=0.002; at the 10th minute: r=0.597, P=0.007; and at the 20th minute: r=0.538, P=0.017). Enzymatic myocardial infarction size was lower in the PCRDS group than in the IS group with peak troponin T (5395±2991 ng/mL versus 8874±1927 ng/mL, P=0.006) and creatine kinase MB (163.6±93.4 IU/L versus 542.2±227.4 IU/L, P<0.001).
Conclusions:
In patients with ST-segment-elevation myocardial infarction, pressure-controlled reperfusion of the culprit vessel by means of gradual reopening of the occluded infarct-related artery (PCRDS) led to better-preserved coronary microvascular integrity and smaller myocardial infarction size, without an increase in procedural complications, compared with IS. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02732080.




J Am Heart Assoc: 16 May 2022:e024172; epub ahead of print
Sezer M, Escaned J, Broyd CJ, Umman B, ... van Royen N, Umman S
J Am Heart Assoc: 16 May 2022:e024172; epub ahead of print | PMID: 35574948
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Abstract

Predicting Residual Angina After Chronic Total Occlusion Percutaneous Coronary Intervention: Insights from the OPEN-CTO Registry.

Butala NM, Tamez H, Secemsky EA, Grantham JA, ... Sapontis J, Yeh RW

Background:
Given that percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) is indicated primarily for symptom relief, identifying patients most likely to benefit is critically important for patient selection and shared decision-making. Therefore, we identified factors associated with residual angina frequency after CTO PCI and developed a model to predict postprocedure anginal burden. Methods and Results Among patients in the OPEN-CTO (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion Hybrid Procedures) registry, we evaluated the association between patient characteristics and residual angina frequency at 6 months, as assessed by the Seattle Angina Questionnaire Angina Frequency Scale. We then constructed a prediction model for angina status after CTO PCI using ordinal regression. Among 901 patients undergoing CTO PCI, 28% had no angina, 31% had monthly angina, 30% had weekly angina, and 12% had daily angina at baseline. Six months later, 53% of patients had a ≥20-point increase in Seattle Angina Questionnaire Angina Frequency Scale score. The final model to predict residual angina after CTO PCI included baseline angina frequency, baseline nitroglycerin use frequency, dyspnea symptoms, depressive symptoms, number of antianginal medications, PCI indication, and presence of multiple CTO lesions and had a C index of 0.78. Baseline angina frequency and nitroglycerin use frequency explained 71% of the predictive power of the model, and the relationship between model components and angina improvement at 6 months varied by baseline angina status.
Conclusions:
A 7-component OPEN-AP (OPEN-CTO Angina Prediction) score can predict angina improvement and residual angina after CTO PCI using variables commonly available before intervention. These findings have implications for appropriate patient selection and counseling for CTO PCI.




J Am Heart Assoc: 16 May 2022:e024056; epub ahead of print
Butala NM, Tamez H, Secemsky EA, Grantham JA, ... Sapontis J, Yeh RW
J Am Heart Assoc: 16 May 2022:e024056; epub ahead of print | PMID: 35574949
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Abstract

Heart Transplantation in Children With Down Syndrome.

Godown J, Fountain D, Bansal N, Ameduri R, ... Villa C, Hollander SA

Background:
Children with Down syndrome (DS) have a high risk of cardiac disease that may prompt consideration for heart transplantation (HTx). However, transplantation in patients with DS is rarely reported. This project aimed to collect and describe waitlist and post- HTx outcomes in children with DS. Methods and Results This is a retrospective case series of children with DS listed for HTx. Pediatric HTx centers were identified by their participation in 2 international registries with centers reporting HTx in a patient with DS providing detailed demographic, medical, surgical, and posttransplant outcome data for analysis. A total of 26 patients with DS were listed for HTx from 1992 to 2020 (median age, 8.5 years; 46% male). High-risk or failed repair of congenital heart disease was the most common indication for transplant (N=18, 69%). A total of 23 (88%) patients survived to transplant. All transplanted patients survived to hospital discharge with a median posttransplant length of stay of 22 days. At a median posttransplant follow-up of 2.8 years, 20 (87%) patients were alive, 2 (9%) developed posttransplant lymphoproliferative disorder, and 8 (35%) were hospitalized for infection within the first year. Waitlist and posttransplant outcomes were similar in patients with and without DS (P=non-significant for all).
Conclusions:
Waitlist and post-HTx outcomes in children with DS selected for transplant listing are comparable to pediatric HTx recipients overall. Given acceptable outcomes, the presence of DS alone should not be considered an absolute contraindication to HTx.




J Am Heart Assoc: 16 May 2022:e024883; epub ahead of print
Godown J, Fountain D, Bansal N, Ameduri R, ... Villa C, Hollander SA
J Am Heart Assoc: 16 May 2022:e024883; epub ahead of print | PMID: 35574952
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Abstract

Ultrashort Door-to-Needle Time for Intravenous Thrombolysis Is Safer and Improves Outcome in the Czech Republic: Nationwide Study 2004 to 2019.

Mikulík R, Bar M, Bělašková S, Černík D, ... Václavík D, Czech Stroke Unit Network

Background:
The benefit of intravenous thrombolysis is time dependent. It remains unclear, however, whether dramatic shortening of door-to-needle time (DNT) among different types of hospitals nationwide does not compromise safety and still improves outcome. Methods and Results Multifaceted intervention to shorten DNT was introduced at a national level, and prospectively collected data from a registry between 2004 and 2019 were analyzed. Generalized estimating equation was used to identify the association between DNT and outcomes independently from prespecified baseline variables. The primary outcome was modified Rankin score 0 to 1 at 3 months, and secondary outcomes were parenchymal hemorrhage/intracerebral hemorrhage (ICH), any ICH, and death. Of 31 316 patients treated with intravenous thrombolysis alone, 18 861 (60%) had available data: age 70±13 years, National Institutes of Health Stroke Scale at baseline (median, 8; interquartile range, 5-14), and 45% men. DNT groups 0 to 20 minutes, 21 to 40 minutes, 41 to 60 minutes, and >60 minutes had 3536 (19%), 5333 (28%), 4856 (26%), and 5136 (27%) patients. National median DNT dropped from 74 minutes in 2004 to 22 minutes in 2019. Shorter DNT had proportional benefit: it increased the odds of achieving modified Rankin score 0 to 1 and decreased the odds of parenchymal hemorrhage/ICH, any ICH, and mortality. Patients with DNT ≤20 minutes, 21 to 40 minutes, and 41 to 60 minutes as compared with DNT >60 minutes had adjusted odds ratios for modified Rankin score 0 to 1 of the following: 1.30 (95% CI, 1.12-1.51), 1.33 (95% CI, 1.15-1.54), and 1.15 (95% CI, 1.02-1.29), and for parenchymal hemorrhage/ICH: 0.57 (95% CI, 0.45-0.71), 0.76 (95% CI, 0.61-0.94), 0.83 (95% CI, 0.70-0.99), respectively.
Conclusions:
Ultrashort initiation of thrombolysis is feasible, improves outcome, and makes treatments safer because of fewer intracerebral hemorrhages. Stroke management should be optimized to initiate thrombolysis as soon as possible optimally within 20 minutes from arrival to a hospital.




J Am Heart Assoc: 16 May 2022:e023524; epub ahead of print
Mikulík R, Bar M, Bělašková S, Černík D, ... Václavík D, Czech Stroke Unit Network
J Am Heart Assoc: 16 May 2022:e023524; epub ahead of print | PMID: 35574953
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Abstract

Surgical Timing in Patients With Infective Endocarditis and With Intracranial Hemorrhage: A Systematic Review and Meta-Analysis.

Musleh R, Schlattmann P, Caldonazo T, Kirov H, ... Günther A, Diab M

Background:
Intracranial hemorrhage (ICH) is one of the main causes for lack of surgery in patients with infective endocarditis (IE), despite the presence of surgical indications. We aimed to evaluate the impact of early surgery in patients with IE and with ICH on postoperative neurological deterioration and all-cause mortality and to elucidate the risk of 30-day mortality in patients who were denied surgery. Methods and Results Three libraries (MEDLINE, EMBASE, and Cochrane Library) were assessed. The primary outcome was all-cause mortality, and the secondary outcome was neurological deterioration. Inverse variance method and random model were performed. We identified 16 studies including 355 patients. Nine studies examined the impact of surgical timing (early versus late) and were included in the meta-analysis. Only one study examined the fate of patients with IE and with ICH who were treated conservatively despite having an indication for cardiac surgery, showing higher mortality rates than those who underwent surgery (11.8% versus 2.5%). We found no significant association between early surgery, regardless of its definition, and a higher mortality (odds ratio [OR], 1.69; 95% CI, 0.95-3.02). Early surgery was associated with higher risk for neurological deterioration (OR, 2.00; 95% CI, 1.10-3.65).
Conclusions:
Cardiac surgery for IE within 30 days of ICH was not associated with higher mortality, but with an increased rate of neurological deterioration. The 30-day mortality in patients with IE and with ICH who were denied surgery has not yet been sufficiently investigated. This patient group should be analyzed in future studies in more detail.




J Am Heart Assoc: 16 May 2022:e024401; epub ahead of print
Musleh R, Schlattmann P, Caldonazo T, Kirov H, ... Günther A, Diab M
J Am Heart Assoc: 16 May 2022:e024401; epub ahead of print | PMID: 35574955
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Abstract

A Biomarker-Enhanced Model for Prediction of Acute Kidney Injury and Cardiovascular Risk Following Angiographic Procedures: CASABLANCA AKI Prediction Substudy.

Mohebi R, van Kimmenade R, McCarthy C, Gaggin H, ... Dangas G, Januzzi JL

Background:
The 2020 Acute Disease Quality Initiative Consensus provided recommendations on novel acute kidney injury biomarkers. In this study, we sought to assess the added value of novel kidney biomarkers to a clinical score in the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) study. Methods and Results We evaluated individuals undergoing coronary and/or peripheral angiography and added 4 candidate biomarkers for acute kidney injury (kidney injury molecule-1, interleukin-18, osteopontin, and cystatin C) to a previously described contrast-associated acute kidney injury (CA-AKI) risk score. Participants were categorized into integer score groups based on the risk assigned by the biomarker-enhanced CA-AKI model. Risk for incident cardiorenal outcomes during a median 3.7 years of follow-up was assessed. Of 1114 participants studied, 55 (4.94%) developed CA-AKI. In adjusted models, neither kidney injury molecule-1 nor interleukin-18 improved discrimination for CA-AKI; addition of osteopontin and cystatin C to the CA-AKI clinical model significantly increased the c-statistic from 0.69 to 0.73 (P for change <0.001) and resulted in a Net Reclassification Index of 59.4. Considering those with the lowest CA-AKI integer score as a reference, the intermediate, high-risk, and very-high-risk groups were associated with adverse cardiorenal outcomes. The corresponding hazard ratios of the very-high-risk group were 3.39 (95% CI, 2.14-5.38) for nonprocedural acute kidney injury, 5.58 (95% CI, 3.23-9.63) for incident chronic kidney disease, 6.21 (95% CI, 3.67-10.47) for myocardial infarction, and 8.94 (95% CI, 4.83-16.53) for all-cause mortality.
Conclusions:
A biomarker-enhanced risk model significantly improves the prediction of CA-AKI beyond clinical variables alone and may stratify the risk of future cardiorenal outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00842868.




J Am Heart Assoc: 16 May 2022:e025729; epub ahead of print
Mohebi R, van Kimmenade R, McCarthy C, Gaggin H, ... Dangas G, Januzzi JL
J Am Heart Assoc: 16 May 2022:e025729; epub ahead of print | PMID: 35574956
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Abstract

Concomitant Hepatorenal Dysfunction and Malnutrition in Valvular Heart Surgery: Long-Term Prognostic Implications for Death and Heart Failure.

Tse YK, Chandramouli C, Li HL, Yu SY, ... Lam CSP, Yiu KH

Background:
Strategies to improve long-term prediction of heart failure and death in valvular surgery are urgently needed because of an increasing number of procedures globally. This study sought to report the prevalence, changes, and prognostic implications of concomitant hepatorenal dysfunction and malnutrition in valvular surgery. Methods and Results In 909 patients undergoing valvular surgery, 3 groups were defined based on hepatorenal function (the modified model for end-stage liver disease excluding international normalized ratio score) and nutritional status (Controlling Nutritional Status score): normal hepatorenal function and nutrition (normal), hepatorenal dysfunction or malnutrition alone (mild), and concomitant hepatorenal dysfunction and malnutrition (severe). Overall, 32%, 46%, and 19% of patients were classified into normal, mild, and severe groups, respectively. Over a 4.1-year median follow-up, mild and severe groups incurred a higher risk of mortality (hazard ratio [HR], 3.17 [95% CI, 1.40-7.17] and HR, 9.30 [95% CI, 4.09-21.16], respectively), cardiovascular death (subdistribution HR, 3.29 [95% CI, 1.14-9.52] and subdistribution HR, 9.29 [95% CI, 3.09-27.99]), heart failure hospitalization (subdistribution HR, 2.11 [95% CI, 1.25-3.55] and subdistribution HR, 3.55 [95% CI, 2.04-6.16]), and adverse outcomes (HR, 2.11 [95% CI, 1.25-3.55] and HR, 3.55 [95% CI, 2.04-6.16]). Modified model for end-stage liver disease excluding international normalized ratio and controlling nutritional status scores improved the predictive ability of European System for Cardiac Operative Risk Evaluation (area under the curve: 0.80 versus 0.73, P<0.001) and Society of Thoracic Surgeons score (area under the curve: 0.79 versus 0.72, P=0.004) for all-cause mortality. One year following surgery (n=707), patients with persistent concomitant hepatorenal dysfunction and malnutrition (severe) experienced worse outcomes than those without.
Conclusions:
Concomitant hepatorenal dysfunction and malnutrition was frequent and strongly linked to heart failure and mortality in valvular surgery.




J Am Heart Assoc: 16 May 2022:e024060; epub ahead of print
Tse YK, Chandramouli C, Li HL, Yu SY, ... Lam CSP, Yiu KH
J Am Heart Assoc: 16 May 2022:e024060; epub ahead of print | PMID: 35574957
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Abstract

Feasibility, Safety, and Short-Term Outcomes of Transcatheter Patent Ductus Arteriosus Closure in Premature Infants on High-Frequency Jet Ventilation.

Shibbani K, Mohammad Nijres B, McLennan D, Bischoff AR, ... Windsor J, Aldoss O

Background:
Prolonged exposure to a hemodynamically significant patent ductus arteriosus (PDA) is associated with major morbidity, particularly in infants born at <27 weeks\' gestation. High-frequency jet ventilation (HFJV) is a standard of care at our center. There are no data about transcatheter PDA closure while on HFJV. The aim of this study was to assess the feasibility, safety, and outcomes of HFJV during transcatheter PDA closure. Methods and Results This is a retrospective cohort study of premature infants undergoing transcatheter device closure on HFJV. The primary outcome was successful device placement. Secondary outcomes included procedure time, fluoroscopy time and dose, time off unit, device complications, need for escalation in respiratory support, and 7-day survival. Subgroup comparative evaluation of patients managed with HFJV versus a small cohort of patients managed with conventional mechanical ventilation was performed. Thirty-eight patients were included in the study. Median age and median weight at PDA device closure for the HFJV cohort were 32 days (interquartile range, 25.25-42.0 days) and 1115 g (interquartile range, 885-1310 g), respectively. There was successful device placement in 100% of patients. There were no device complications noted. The time off unit and the procedure time were not significantly different between the HFJV group and the conventional ventilation group. Infants managed by HFJV had shorter median fluoroscopy times (4.5 versus 6.1 minutes; P<0.05) and no increased risk of adverse respiratory outcomes.
Conclusions:
Transcatheter PDA closure in premature infants on HFJV is a safe and effective approach that does not compromise device placement success rate and does not lead to secondary complications.




J Am Heart Assoc: 16 May 2022:e025343; epub ahead of print
Shibbani K, Mohammad Nijres B, McLennan D, Bischoff AR, ... Windsor J, Aldoss O
J Am Heart Assoc: 16 May 2022:e025343; epub ahead of print | PMID: 35574958
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Abstract

Clinical Prediction Models for Heart Failure Hospitalization in Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Razaghizad A, Oulousian E, Randhawa VK, Ferreira JP, ... Ezekowitz J, Sharma A

Background:
Clinical prediction models have been developed for hospitalization for heart failure in type 2 diabetes. However, a systematic evaluation of these models\' performance, applicability, and clinical impact is absent. Methods and Results We searched Embase, MEDLINE, Web of Science, Google Scholar, and Tufts\' clinical prediction registry through February 2021. Studies needed to report the development, validation, clinical impact, or update of a prediction model for hospitalization for heart failure in type 2 diabetes with measures of model performance and sufficient information for clinical use. Model assessment was done with the Prediction Model Risk of Bias Assessment Tool, and meta-analyses of model discrimination were performed. We included 15 model development and 3 external validation studies with data from 999 167 people with type 2 diabetes. Of the 15 models, 6 had undergone external validation and only 1 had low concern for risk of bias and applicability (Risk Equations for Complications of Type 2 Diabetes). Seven models were presented in a clinically useful manner (eg, risk score, online calculator) and 2 models were classified as the most suitable for clinical use based on study design, external validity, and point-of-care usability. These were Risk Equations for Complications of Type 2 Diabetes (meta-analyzed c-statistic, 0.76) and the Thrombolysis in Myocardial Infarction Risk Score for Heart Failure in Diabetes (meta-analyzed c-statistic, 0.78), which was the simplest model with only 5 variables. No studies reported clinical impact.
Conclusions:
Most prediction models for hospitalization for heart failure in patients with type 2 diabetes have potential concerns with risk of bias or applicability, and uncertain external validity and clinical impact. Future research is needed to address these knowledge gaps.




J Am Heart Assoc: 16 May 2022:e024833; epub ahead of print
Razaghizad A, Oulousian E, Randhawa VK, Ferreira JP, ... Ezekowitz J, Sharma A
J Am Heart Assoc: 16 May 2022:e024833; epub ahead of print | PMID: 35574959
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Abstract

Invasive Hemodynamic Predictors of Survival in Patients With Mitral Stenosis Secondary to Mitral Annular Calcification.

El Sabbagh A, Nishimura RA, Eleid MF, Pislaru SV, ... Hodge DO, Miranda WR

Background:
The aim of this study was to establish prognostic hemodynamic parameters in patients with mitral stenosis secondary to mitral annular calcification. Methods and Results A retrospective cohort of 105 patients undergoing transseptal catheterization for hemodynamic evaluation of mitral annular calcification-related mitral stenosis between 2004 and 2020 was studied. Mitral valve gradient (MVG) and mitral valve area (MVA; calculated by the Gorlin formula) were measured using direct left atrial and left ventricular pressures. The median age of the patients was 70.3 years (58.4-76.7 years), and 53.3% were women. The median MVA was 1.7 cm2 (1.3-2.3 cm2) and MVG was 7.3 mm Hg (5.3-10.3 mm Hg); left ventricular end-diastolic pressure was 17.6±28.3 mm Hg. During a median of 2.1 years (0.7-4.5 years), there were 63 deaths; 1- and 5-year survival were 76% and 40%, respectively. There was no association between left ventricular end-diastolic pressure and survival. After adjusting for age and comorbidities, both MVA (hazard ratio [HR], 0.50 per cm2; 95% CI, 0.34-0.73) and MVG (HR, 1.1 per mm Hg; 95% CI, 1.05-1.20) were independent predictors of death. Atrial fibrillation was also independently associated with mortality. When added to a combined model, MVA remained associated with death (HR, 0.51 per cm2; 95% CI, 0.33-0.79) while MVG was not.
Conclusions:
In patients with mitral annular calcification-related mitral stenosis, survival was poor. MVA and MVG were independently associated with death, but MVA was a better predictor of outcomes.




J Am Heart Assoc: 16 May 2022:e023107; epub ahead of print
El Sabbagh A, Nishimura RA, Eleid MF, Pislaru SV, ... Hodge DO, Miranda WR
J Am Heart Assoc: 16 May 2022:e023107; epub ahead of print | PMID: 35574960
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Abstract

Nitrite Generating and Depleting Capacity of the Oral Microbiome and Cardiometabolic Risk: Results from ORIGINS.

Goh CE, Bohn B, Marotz C, Molinsky R, ... Knight R, Demmer RT

Background:
The enterosalivary nitrate-nitrite-nitric oxide (NO3-NO2-NO) pathway generates NO following oral microbiota-mediated production of salivary nitrite, potentially linking the oral microbiota to reduced cardiometabolic risk. Nitrite depletion by oral bacteria may also be important for determining the net nitrite available systemically. We examine if higher abundance of oral microbial genes favoring increased oral nitrite generation and decreased nitrite depletion is associated with a better cardiometabolic profile cross-sectionally. Methods and Results This study includes 764 adults (mean [SD] age 32 [9] years, 71% women) enrolled in ORIGINS (Oral Infections, Glucose Intolerance, and Insulin Resistance Study). Microbial DNA from subgingival dental plaques underwent 16S rRNA gene sequencing; PICRUSt2 was used to estimate functional gene profiles. To represent the different components and pathways of nitrogen metabolism in bacteria, predicted gene abundances were operationalized to create summary scores by (1) bacterial nitrogen metabolic pathway or (2) biochemical product (NO2, NO, or ammonia [NH3]) formed by the action of the bacterial reductases encoded. Finally, nitrite generation-to-depletion ratios of gene abundances were created from the above summary scores. A composite cardiometabolic Z score was created from cardiometabolic risk variables, with higher scores associated with worse cardiometabolic health. We performed multivariable linear regression analysis with cardiometabolic Z score as the outcome and the gene abundance summary scores and ratios as predictor variables, adjusting for sex, age, race, and ethnicity in the simple adjusted model. A 1 SD higher NO versus NH3 summary ratio was inversely associated with a -0.10 (false discovery rate q=0.003) lower composite cardiometabolic Z score in simple adjusted models. Higher NH3 summary score (suggestive of nitrite depletion) was associated with higher cardiometabolic risk, with a 0.06 (false discovery rate q=0.04) higher composite cardiometabolic Z score.
Conclusions:
Increased net capacity for nitrite generation versus depletion by oral bacteria, assessed through a metagenome estimation approach, is associated with lower levels of cardiometabolic risk.




J Am Heart Assoc: 16 May 2022:e023038; epub ahead of print
Goh CE, Bohn B, Marotz C, Molinsky R, ... Knight R, Demmer RT
J Am Heart Assoc: 16 May 2022:e023038; epub ahead of print | PMID: 35574962
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Impact:
Abstract

Chronic Stroke Sensorimotor Impairment Is Related to Smaller Hippocampal Volumes: An ENIGMA Analysis.

Zavaliangos-Petropulu A, Lo B, Donnelly MR, Schweighofer N, ... Thompson PM, Liew SL

Background:
Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper-limb sensorimotor impairment. We investigated associations between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross-sectional T1-weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta-Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA-UE (Fugl-Meyer Assessment of Upper Extremity). Robust mixed-effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; β=0.16) but not contralesional (P=0.96; β=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; β=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; β=-0.26) and contralesional (P=0.006; β=-0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; β=-0.21) and extent of sensorimotor damage (P=0.003; β=-0.15).
Conclusions:
The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.




J Am Heart Assoc: 16 May 2022:e025109; epub ahead of print
Zavaliangos-Petropulu A, Lo B, Donnelly MR, Schweighofer N, ... Thompson PM, Liew SL
J Am Heart Assoc: 16 May 2022:e025109; epub ahead of print | PMID: 35574963
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Abstract

Sex Differences in Intracranial Atherosclerosis in Patients With Hypertension With Acute Ischemic Stroke.

Song JW, Xiao J, Cen SY, Liu X, ... Song SS, Fan Z

Background:
Studies suggest the presence of sex differences in hypertension prevalence and its associated outcomes in atherosclerosis and stroke. We hypothesized a higher intracranial atherosclerosis burden among men with hypertension and acute ischemic stroke compared with women. Methods and Results A multicenter retrospective study was performed from a prospective database identifying patients with hypertension presenting with intracranial atherosclerosis-related acute ischemic stroke and imaged with intracranial vessel wall magnetic resonance imaging. Proximal and distal plaques on vessel wall magnetic resonance imaging were scored. Negative binomial models assessed the associations between plaque-count and sex and the interaction between sex and treatment. Covariates were selected by a least absolute shrinkage and selection operator procedure. Sixty-one patients (n=42 men) were included. There were no significant differences in demographic or cardiovascular risk factors except for smoking history (P=0.002). Adjusted total and proximal plaque counts for men were 1.6 (95% CI, 1.2-2.1; P<0.01) and 1.4 (95% CI, 1.0-1.9; P=0.03) times as high as women, respectively. Female sex was more protective for proximal plaque if treated for hypertension. The risk ratio of men versus women was 1.5 (95% CI, 1.0-2.1) for treated patients. The risk ratio of men versus women was 0.7 (95% CI, 0.4-1.3) for untreated patients. The relative difference between these 2 risk ratios was 2.0 (95% CI, 1.1-3.9), which was statistically significant from the interaction test, P=0.04.
Conclusions:
Men with hypertension with acute ischemic stroke have significantly higher total and proximal plaque burdens than women. Women with hypertension on anti-hypertensive medication showed a greater reduction in proximal plaque burden than men. Further confirmation with a longitudinal cohort study is needed and may help evaluate whether different treatment guidelines for managing hypertension by sex can help reduce intracranial atherosclerosis burden and ultimately acute ischemic stroke risk.




J Am Heart Assoc: 16 May 2022:e025579; epub ahead of print
Song JW, Xiao J, Cen SY, Liu X, ... Song SS, Fan Z
J Am Heart Assoc: 16 May 2022:e025579; epub ahead of print | PMID: 35574965
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Impact:
Abstract

CENIT (Impact of Cardiac Exercise Training on Lipid Content in Coronary Atheromatous Plaques Evaluated by Near-Infrared Spectroscopy): A Randomized Trial.

Vesterbekkmo EK, Madssen E, Aamot Aksetøy IL, Follestad T, ... Wisløff U, Wiseth R

Background:
The effect of physical exercise on lipid content of coronary artery plaques is unknown. With near infrared spectroscopy we measured the effect of high intensity interval training (HIIT) on lipid content in coronary plaques in patients with stable coronary artery disease following percutaneous coronary intervention. Methods and Results In CENIT (Impact of Cardiac Exercise Training on Lipid Content in Coronary Atheromatous Plaques Evaluated by Near-Infrared Spectroscopy) 60 patients were randomized to 6 months supervised HIIT or to a control group. The primary end point was change in lipid content measured as maximum lipid core burden index at 4 mm (maxLCBI4mm). A predefined cutoff of maxLCBI4mm >100 was required for inclusion in the analysis. Forty-nine patients (HIIT=20, usual care=29) had maxLCBI4mm >100 at baseline. Change in maxLCBI4mm did not differ between groups (-1.2, 95% CI, -65.8 to 63.4, P=0.97). The estimated reduction in maxLCBI4mm was -47.7 (95% CI, -100.3 to 5.0, P=0.075) and -46.5 (95% CI, -87.5 to -5.4, P=0.027) after HIIT and in controls, respectively. A negative correlation was observed between change in peak oxygen uptake (VO2peak) and change in lipid content (Spearman\'s correlation -0.44, P=0.009). With an increase in VO2peak above 1 metabolic equivalent task, maxLCBI4mm was on average reduced by 142 (-8 to -262), whereas the change was -3.2 (154 to -255) with increased VO2peak below 1 metabolic equivalent task.
Conclusions:
Six months of HIIT following percutaneous coronary intervention did not reduce lipid content in coronary plaques compared with usual care. A moderate negative correlation between increase in VO2peak and change in lipid content generates the hypothesis that exercise with a subsequent increase in fitness may reduce lipid content in coronary atheromatous plaques. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02494947.




J Am Heart Assoc: 16 May 2022:e024705; epub ahead of print
Vesterbekkmo EK, Madssen E, Aamot Aksetøy IL, Follestad T, ... Wisløff U, Wiseth R
J Am Heart Assoc: 16 May 2022:e024705; epub ahead of print | PMID: 35574968
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Impact:
Abstract

Effect of Heart Rate on 1-Year Outcome for Patients With Acute Ischemic Stroke.

Lee KJ, Kim BJ, Han MK, Kim JT, ... Bae HJ, CRCS‐K (Clinical Research Collaboration for Stroke in Korea) Investigators

Background:
Previous literature about the effect of heart rate on poststroke outcomes is limited. We attempted to elucidate (1) whether heart rate during the acute period of ischemic stroke predicts subsequent major clinical events, (2) which heart rate parameter is best for prediction, and (3) what is the estimated heart rate cutoff point for the primary outcome. Methods and Results Eight thousand thirty-one patients with acute ischemic stroke who were hospitalized within 48 hours of onset were analyzed retrospectively. Heart rates between the 4th and 7th day after onset were collected and heart rate parameters including mean, time-weighted average, maximum, and minimum heart rate were evaluated. The primary outcome was the composite of recurrent stroke, myocardial infarction, and mortality up to 1 year after stroke onset. All heart rate parameters were associated with the primary outcome (P\'s<0.001). Maximum heart rate had the highest predictive power. The estimated cutoff point for the primary outcome was 81 beats per minute for mean heart rate and 100 beats per minute for maximum heart rate. Patients with heart rates above these cutoff points had a higher risk of the primary outcome (adjusted hazard ratio, 1.80 [95% CI, 1.57-2.06] for maximum heart rate and 1.65 [95% CI, 1.45-1.89] for mean heart rate). The associations were replicated in a separate validation dataset (N=10 000).
Conclusions:
These findings suggest that heart rate during the acute period of ischemic stroke is a predictor of major clinical events, and optimal heart rate control might be a target for preventing subsequent cardiovascular events.




J Am Heart Assoc: 10 May 2022:e025861; epub ahead of print
Lee KJ, Kim BJ, Han MK, Kim JT, ... Bae HJ, CRCS‐K (Clinical Research Collaboration for Stroke in Korea) Investigators
J Am Heart Assoc: 10 May 2022:e025861; epub ahead of print | PMID: 35535617
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Abstract

Early versus late Catheter Ablation of Atrial Fibrillation and Risk of Permanent Pacemaker Implantation in patients with underlying Sinus Node Dysfunction.

Umer Butt M, Okumus N, Jabri A, Thomas C, Tarabichi Y, Karim S

Background:
Atrial fibrillation (AF) is associated with anatomical and electrical remodeling. Some patients with AF have concomitant sick sinus syndrome (SSS) and may need permanent pacemaker (PPM) implantation. Association between catheter ablation of AF (CA) timing and need for PPM in SSS has not been assessed. Methods and Results We used pooled electronic health data to perform retrospective cross-sectional analysis of 66,595 patients with AF and SSS to assess the need of PPM implantation temporally with atrial fibrillation performed earlier within 5 years (group 1), 5-10 years (group 2), or beyond 10 years (group 3) of diagnosis. PPM implantation was lowest amongst those who had CA within 5 years of SSS diagnosis; group 1 versus group 2 (18.15 % vs 27.21 %) and group 1 versus group 3 (18.15 % vs 27.22%). Interestingly, there was no difference in risk of PPM between group 2 and group 3 (27.21 % vs 27.22 %, OR 1.00 [0.85- 1.20]).
Conclusion:
Even after controlling known risk factors that increase the need for pacemaker implantation, timing of AF ablation was the strongest predictor for need for PPM. Patients adjusted odds (aOR) of PPM was lower if patient had CA within 5 years of diagnosis as compared to later than 5 years (aOR 0.64 [0.59- 0.70]).




J Am Heart Assoc: 10 May 2022:e023333; epub ahead of print
Umer Butt M, Okumus N, Jabri A, Thomas C, Tarabichi Y, Karim S
J Am Heart Assoc: 10 May 2022:e023333; epub ahead of print | PMID: 35535620
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Impact:
Abstract

Remnant Cholesterol Predicts Risk of Cardiovascular Events in Patients With Myocardial Infarction With Nonobstructive Coronary Arteries.

Gao S, Xu H, Ma W, Yuan J, Yu M

Background:
Remnant cholesterol (RC) has been reported to promote atherosclerotic cardiovascular disease. Yet little is known regarding the RC-related residual risk in patients with myocardial infarction (MI) with nonobstructive coronary arteries. Methods and Results A total of 1179 patients with MI with nonobstructive coronary arteries were enrolled and divided according to median level of RC calculated as non-high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol. The primary end point was a composite of major adverse cardiovascular events (MACEs), including all-cause death, nonfatal MI, stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan-Meier, Cox regression, and receiver-operating characteristic analyses were used. Patients with higher median level of RC had a significantly higher incidence of MACEs (16.9% versus 11.5%; P=0.009) over the median follow-up of 41.7 months. High RC levels were significantly associated with an increased risk of MACEs after adjustment for multiple clinically relevant variables (per 1 SD increase, hazard ratio, 0.61; 95% CI, 1.12-2.31; P=0.009). Elevated RC also contributed to residual risk beyond conventional lipid parameters. Moreover, RC had an area under the curve of 0.61 for MACE prediction. When adding RC to the Thrombolysis in Myocardial Infarction risk score, the combined model yielded a significant improvement in discrimination for MACEs.
Conclusions:
Elevated RC was closely associated with poor outcomes after MI with nonobstructive coronary arteries independent of traditional risk factors, indicating the utility of RC for risk stratification and a rationale for targeted RC-lowering trials in patients with MI with nonobstructive coronary arteries.




J Am Heart Assoc: 10 May 2022:e024366; epub ahead of print
Gao S, Xu H, Ma W, Yuan J, Yu M
J Am Heart Assoc: 10 May 2022:e024366; epub ahead of print | PMID: 35535621
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Impact:
Abstract

Prior Freezing Has Minimal Impact on the Contractile Properties of Permeabilized Human Myocardium.

Milburn GN, Moonschi F, White AM, Thompson M, ... Birks EJ, Campbell KS

Background:
Experiments measuring the contractile properties of human myocardium are important for translational research but complicated by the logistical difficulties of acquiring specimens. Accordingly, many groups perform contractile assays using samples that are acquired from patients at one institution and shipped to another institution for experiments. This necessitates freezing the samples and performing subsequent assays using chemically permeabilized preparations. It is unknown how prior freezing affects the contractile function of these preparations. Methods and Results To examine the effects of freezing we measured the contractile function of never-frozen and previously frozen myocardial samples. Samples of left ventricular tissue were obtained from 7 patients who were having a ventricular assist device implanted. Half of each sample was chemically permeabilized and used immediately for contractile assays. The other half of the sample was snap frozen in liquid nitrogen and maintained at -180 °C for at least 6 months before being thawed and tested in a second series of experiments. Maximum isometric force measured in pCa 4.5 solution, passive force measured in pCa 9.0 solution, and Hill coefficients were not influenced by prior freezing (P=0.07, P=0.14, and P=0.27 respectively). pCa50 in never-frozen samples (6.11±0.04) was statistically greater (P<0.001) than that measured after prior freezing (5.99±0.04) but the magnitude of the effect was only ≈0.1 pCa units.
Conclusions:
We conclude that prior freezing has minimal impact on the contractile properties that can be measured using chemically permeabilized human myocardium.




J Am Heart Assoc: 10 May 2022:e023010; epub ahead of print
Milburn GN, Moonschi F, White AM, Thompson M, ... Birks EJ, Campbell KS
J Am Heart Assoc: 10 May 2022:e023010; epub ahead of print | PMID: 35535623
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Impact:
Abstract

Left Atrial Decompression in Pediatric Patients Supported With Extracorporeal Membrane Oxygenation for Failure to Wean From Cardiopulmonary Bypass: A Propensity-Weighted Analysis.

Sperotto F, Polito A, Amigoni A, Maschietto N, Thiagarajan RR

Background:
Left atrial (LA) decompression on extracorporeal membrane oxygenation (ECMO) can reduce left ventricular distension, allowing myocardial rest and recovery, and protect from lung injury secondary to cardiogenic pulmonary edema. However, clinical benefits remain unknown. We sought to evaluate the association between LA decompression and in-hospital adverse outcome (mortality, transplant on ECMO, or conversion to ventricular assist device) in patients who failed to wean from cardiopulmonary bypass using a propensity score to adjust for baseline differences. Methods and Results Children (aged <18 years) with biventricular physiology supported with ECMO for failure to wean from cardiopulmonary bypass after cardiac surgery from 2000 through 2016, reported to the ELSO (Extracorporeal Life Support Organization) Registry, were included. Inverse probability of treatment weighted logistic regression was used to test the association between LA decompression and in-hospital adverse outcomes. Of the 2915 patients supported with venoarterial ECMO for failure to wean from cardiopulmonary bypass, 1508 had biventricular physiology and 279 (18%) underwent LA decompression (LA+). Genetic and congenital abnormalities (P=0.001) and pulmonary hypertension (P=0.010) were less frequent and baseline arrhythmias (P=0.022) were more frequent in LA+ patients. LA+ patients had longer pre-ECMO mechanical ventilation and CBP time (P<0.001), and used aortic cross-clamp (P=0.001) more frequently. Covariates were well balanced between the propensity-weighted cohorts. In-hospital adverse outcomes occurred in 47% of LA+ patients and 51% of the others. Weighted multivariate logistic regression showed LA decompression to be protective for in-hospital adverse outcomes (adjusted odds ratio, 0.775 [95% CI, 0.644-0.932]).
Conclusions:
LA decompression independently decreased the risk of in-hospital adverse outcome in pediatric venoarterial ECMO patients who failed to wean from cardiopulmonary bypass, suggesting that these patients may benefit from LA decompression.




J Am Heart Assoc: 10 May 2022:e023963; epub ahead of print
Sperotto F, Polito A, Amigoni A, Maschietto N, Thiagarajan RR
J Am Heart Assoc: 10 May 2022:e023963; epub ahead of print | PMID: 35535596
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Impact:
Abstract

Estimated Pulse Wave Velocity Is Associated With All-Cause Mortality During 8.5 Years Follow-up in Patients Undergoing Elective Coronary Angiography.

Laugesen E, Olesen KKW, Peters CD, Buus NH, ... Botker HE, Poulsen PL

Background:
Estimated pulse wave velocity (ePWV) calculated by equations using age and blood pressure has been suggested as a new marker of mortality and cardiovascular risk. However, the prognostic potential of ePWV during long-term follow-up in patients with symptoms of stable angina remains unknown. Methods and Results In this study, ePWV was calculated in 25 066 patients without diabetes, previous myocardial infarction (MI), stroke, heart failure, or valvular disease (mean age 63.7±10.5 years, 58% male) with stable angina pectoris undergoing elective coronary angiography during 2003 to 2016. Multivariable Cox models were used to assess the association with incident all-cause mortality, MI, and stroke. Discrimination was assessed using Harrell´s C-index. During a median follow-up period of 8.5 years (interquartile range 5.5-11.3 years), 779 strokes, 1233 MIs, and 4112 deaths were recorded. ePWV was associated with all-cause mortality (hazard ratio [HR] per 1 m/s, 1.13; 95% CI, 1.05-1.21) and MI (HR per 1 m/s 1.23, 95% CI, 1.09-1.39) after adjusting for age, systolic blood pressure, body mass index, smoking, estimated glomerular filtration rate, Charlson Comorbidity Index score, antihypertensive treatment, statins, aspirin, and number of diseased coronary arteries. Compared with traditional risk factors, the adjusted model with ePWV was associated with a minor but likely not clinically relevant increase in discrimination for mortality, 76.63% with ePWV versus 76.56% without ePWV, P<0.05.
Conclusions:
In patients with stable angina pectoris, ePWV was associated with all-cause mortality and MI beyond traditional risk factors. However, the added prediction of mortality was not improved to a clinically relevant extent.




J Am Heart Assoc: 10 May 2022:e025173; epub ahead of print
Laugesen E, Olesen KKW, Peters CD, Buus NH, ... Botker HE, Poulsen PL
J Am Heart Assoc: 10 May 2022:e025173; epub ahead of print | PMID: 35535599
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Impact:
Abstract

Incidence and Prognostic Implications of Readmissions Caused by Thrombotic Events After a Heart Failure Hospitalization.

Chaudhury P, Alvarez P, Michael M, Saad M, ... Desai M, Mentias A

Background:
Readmission occurs in 1 out of 3 patients with heart failure (HF). We aimed to study the incidence and prognostic implications of rehospitalizations because of arterial thromboembolism events (ATEs) and venous thromboembolism events (VTEs) after discharge in patients with HF. Methods and Results We identified Medicare beneficiaries who were admitted with a primary diagnosis of HF from 2014 to 2019, with a hospital stay ranging between 3 and10 days, followed by discharge to home. We calculated incidence of ATEs (myocardial infarction, ischemic stroke, or systemic embolism) and VTEs (deep venous thrombosis and pulmonary embolism) up to 90 days after discharge. Out of 2 953 299 patients admitted with HF during the study period, a total of 585 353 patients met the inclusion criteria, and 36.6% were readmitted within 90 days of discharge. The incidence of readmission due ATEs, VTEs, HF, and all other reasons was 3.4%, 0.5%, 13.2%, and 19.5%, respectively. Incidence of thromboembolic events was highest within 14 days after discharge. Factors associated with ATEs included prior coronary, peripheral, or cerebrovascular disease and for VTEs included malignancy and prior liver or lung disease. ATE/VTE readmission had a 30-day mortality of 19.9%. After a median follow-up period of 25.6 months, ATE and VTE readmissions were associated with higher risk of mortality (hazard ratio, 2.76 [95% CI, 2.71-2.81] and 2.17 [95% CI, 2.08-2.27], respectively; P<0.001 for both) compared with no readmission on time-dependent Cox regression.
Conclusions:
After a HF hospitalization, 3.9% of patients were readmitted with a thromboembolic event that was associated with 2- to 3-fold greater risk of mortality in follow-up.




J Am Heart Assoc: 10 May 2022:e025342; epub ahead of print
Chaudhury P, Alvarez P, Michael M, Saad M, ... Desai M, Mentias A
J Am Heart Assoc: 10 May 2022:e025342; epub ahead of print | PMID: 35535610
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Impact:
Abstract

Myeloid Poldip2 Contributes to the Development of Pulmonary Inflammation by Regulating Neutrophil Adhesion in a Murine Model of Acute Respiratory Distress Syndrome.

Ou Z, Dolmatova E, Mandavilli R, Qu H, ... Hernandes MS, Griendling KK

Background:
Lung injury, a severe adverse outcome of lipopolysaccharide-induced acute respiratory distress syndrome, is attributed to excessive neutrophil recruitment and effector response. Poldip2 (polymerase δ-interacting protein 2) plays a critical role in regulating endothelial permeability and leukocyte recruitment in acute inflammation. Thus, we hypothesized that myeloid Poldip2 is involved in neutrophil recruitment to inflamed lungs. Methods and Results After characterizing myeloid-specific Poldip2 knockout mice, we showed that at 18 hours post-lipopolysaccharide injection, bronchoalveolar lavage from myeloid Poldip2-deficient mice contained fewer inflammatory cells (8 [4-16] versus 29 [12-57]×104/mL in wild-type mice) and a smaller percentage of neutrophils (30% [28%-34%] versus 38% [33%-41%] in wild-type mice), while the main chemoattractants for neutrophils remained unaffected. In vitro, Poldip2-deficient neutrophils responded as well as wild-type neutrophils to inflammatory stimuli with respect to neutrophil extracellular trap formation, reactive oxygen species production, and induction of cytokines. However, neutrophil adherence to a tumor necrosis factor-α stimulated endothelial monolayer was inhibited by Poldip2 depletion (225 [115-272] wild-type [myePoldip2+/+] versus 133 [62-178] myeloid-specific Poldip2 knockout [myePoldip2-/-] neutrophils) as was transmigration (1.7 [1.3-2.1] versus 1.1 [1.0-1.4] relative to baseline transmigration). To determine the underlying mechanism, we examined the surface expression of β2-integrin, its binding to soluble intercellular adhesion molecule 1, and Pyk2 phosphorylation. Surface expression of β2-integrins was not affected by Poldip2 deletion, whereas β2-integrins and Pyk2 were less activated in Poldip2-deficient neutrophils.
Conclusions:
These results suggest that myeloid Poldip2 is involved in β2-integrin activation during the inflammatory response, which in turn mediates neutrophil-to-endothelium adhesion in lipopolysaccharide-induced acute respiratory distress syndrome.




J Am Heart Assoc: 10 May 2022:e025181; epub ahead of print
Ou Z, Dolmatova E, Mandavilli R, Qu H, ... Hernandes MS, Griendling KK
J Am Heart Assoc: 10 May 2022:e025181; epub ahead of print | PMID: 35535614
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Impact:
Abstract

Sex and Race Differences in the Evaluation and Treatment of Young Adults Presenting to the Emergency Department With Chest Pain.

Banco D, Chang J, Talmor N, Wadhera P, ... Safdar B, Reynolds HR

Background:
Acute myocardial infarctions are increasingly common among young adults. We investigated sex and racial differences in the evaluation of chest pain (CP) among young adults presenting to the emergency department. Methods and Results Emergency department visits for adults aged 18 to 55 years presenting with CP were identified in the National Hospital Ambulatory Medical Care Survey 2014 to 2018, which uses stratified sampling to produce national estimates. We evaluated associations between sex, race, and CP management before and after multivariable adjustment. We identified 4152 records representing 29 730 145 visits for CP among young adults. Women were less likely than men to be triaged as emergent (19.1% versus 23.3%, respectively, P<0.001), to undergo electrocardiography (74.2% versus 78.8%, respectively, P=0.024), or to be admitted to the hospital or observation unit (12.4% versus 17.9%, respectively, P<0.001), but ordering of cardiac biomarkers was similar. After multivariable adjustment, men were seen more quickly (hazard ratio [HR], 1.15 [95% CI, 1.05-1.26]) and were more likely to be admitted (adjusted odds ratio, 1.40 [95% CI, 1.08-1.81]; P=0.011). People of color waited longer for physician evaluation (HR, 0.82 [95% CI, 0.73-0.93]; P<0.001) than White adults after multivariable adjustment, but there were no racial differences in hospital admission, triage level, electrocardiography, or cardiac biomarker testing. Acute myocardial infarction was diagnosed in 1.4% of adults in the emergency department and 6.5% of admitted adults.
Conclusions:
Women and people of color with CP waited longer to be seen by physicians, independent of clinical features. Women were independently less likely to be admitted when presenting with CP. These differences could impact downstream treatment and outcomes.




J Am Heart Assoc: 04 May 2022:e024199; epub ahead of print
Banco D, Chang J, Talmor N, Wadhera P, ... Safdar B, Reynolds HR
J Am Heart Assoc: 04 May 2022:e024199; epub ahead of print | PMID: 35506534
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Impact:
Abstract

Fractional Flow Reserve Versus Instantaneous Wave-Free Ratio in Assessment of Lesion Hemodynamic Significance and Explanation of their Discrepancies. International, Multicenter and Prospective Trial: The FiGARO Study.

Kovarnik T, Hitoshi M, Kral A, Jerabek S, ... Linhart A, FiGARO trial investigators

Background:
The FiGARO (FFR versus iFR in Assessment of Hemodynamic Lesion Significance, and an Explanation of Their Discrepancies) trial is a prospective registry searching for predictors of fractional flow reserve/instantaneous wave-free ratio (FFR/iFR) discrepancy. Methods and Results FFR/iFR were analyzed using a Verrata wire, and coronary flow reserve was analyzed using a Combomap machine (both Philips-Volcano). The risk polymorphisms for endothelial nitric oxide synthase and for heme oxygenase-1 were analyzed. In total, 1884 FFR/iFR measurements from 1564 patients were included. The FFR/iFR discrepancy occurred in 393 measurements (20.9%): FFRp (positive)/iFRn (negative) type (264 lesions, 14.0%) and FFRn/iFRp (129 lesions, 6.8%) type. Coronary flow reserve was measured in 343 lesions, correlating better with iFR (R=0.56, P<0.0001) than FFR (R=0.36, P<0.0001). The coronary flow reserve value in FFRp/iFRn lesions (2.24±0.7) was significantly higher compared with both FFRp/iFRp (1.39±0.36), and FFRn/iFRn lesions (1.8±0.64, P<0.0001). Multivariable logistic regression analysis confirmed (1) sex, age, and lesion location in the right coronary artery as predictors for FFRp/iFRn discrepancy; and (2) hemoglobin level, smoking, and renal insufficiency as predictors for FFRn/iFRp discrepancy. The FFRn/iFRp type of discrepancy was significantly more frequent in patients with both risk types of polymorphisms (endothelial nitric oxide synthaser+heme oxygenase-1r): 8 patients (24.2%) compared with FFRp/iFRn type of discrepancy: 2 patients (5.9%), P=0.03.
Conclusions:
Predictors for FFRp/iFRn discrepancy were sex, age, and location in the right coronary artery. Predictors for FFRn/iFRp were hemoglobin level, smoking, and renal insufficiency. The risk type of polymorphism in endothelial nitric oxide synthase and heme oxygenase-1 genes was more frequently found in patients with FFRn/iFRp type of discrepancy. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03033810.




J Am Heart Assoc: 03 May 2022; 11:e021490
Kovarnik T, Hitoshi M, Kral A, Jerabek S, ... Linhart A, FiGARO trial investigators
J Am Heart Assoc: 03 May 2022; 11:e021490 | PMID: 35502771
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Impact:
Abstract

Comparisons of Prehospital Delay and Related Factors Between Acute Ischemic Stroke and Acute Myocardial Infarction.

Yoon CW, Oh H, Lee J, Rha JH, ... Lee K, Bae HJ

Background:
Prehospital delay is an important contributor to poor outcomes in both acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We aimed to compare the prehospital delay and related factors between AIS and AMI. Methods and Results We identified patients with AIS and AMI who were admitted to the 11 Korean Regional Cardiocerebrovascular Centers via the emergency room between July 2016 and December 2018. Delayed arrival was defined as a prehospital delay of >3 hours, and the generalized linear mixed-effects model was applied to explore the effects of potential predictors on delayed arrival. This study included 17 895 and 8322 patients with AIS and AMI, respectively. The median value of prehospital delay was 6.05 hours in AIS and 3.00 hours in AMI. The use of emergency medical services was the key determinant of delayed arrival in both groups. Previous history, 1-person household, weekday presentation, and interhospital transfer had higher odds of delayed arrival in both groups. Age and sex had no or minimal effects on delayed arrival in AIS; however, age and female sex were associated with higher odds of delayed arrival in AMI. More severe symptoms had lower odds of delayed arrival in AIS, whereas no significant effect was observed in AMI. Off-hour presentation had higher and prehospital awareness had lower odds of delayed arrival; however, the magnitude of their effects differed quantitatively between AIS and AMI.
Conclusions:
The effects of some nonmodifiable and modifiable factors on prehospital delay differed between AIS and AMI. A differentiated strategy might be required to reduce prehospital delay.




J Am Heart Assoc: 02 May 2022:e023214; epub ahead of print
Yoon CW, Oh H, Lee J, Rha JH, ... Lee K, Bae HJ
J Am Heart Assoc: 02 May 2022:e023214; epub ahead of print | PMID: 35491981
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Abstract

IV Sotalol Use in Pediatric and Congenital Heart Patients: A Multicenter Registry Study.

Malloy-Walton LE, Von Bergen NH, Balaji S, Fischbach PS, ... Avari Silva JN, Saul JP

Background:
There is limited information regarding the clinical use and effectiveness of IV sotalol in pediatric patients and patients with congenital heart disease, including those with severe myocardial dysfunction. A multicenter registry study was designed to evaluate the safety, efficacy, and dosing of IV sotalol. Methods and Results A total of 85 patients (age 1 day-36 years) received IV sotalol, of whom 45 (53%) had additional congenital cardiac diagnoses and 4 (5%) were greater than 18 years of age. In 79 patients (93%), IV sotalol was used to treat supraventricular tachycardia and 4 (5%) received it to treat ventricular arrhythmias. Severely decreased cardiac function by echocardiography was seen before IV sotalol in 7 (9%). The average dose was 1 mg/kg (range 0.5-1.8 mg/kg/dose) over a median of 60 minutes (range 30-300 minutes). Successful arrhythmia termination occurred in 31 patients (49%, 95% CI [37%-62%]) with improvement in rhythm control defined as rate reduction permitting overdrive pacing in an additional 18 patients (30%, 95% CI [19%-41%]). Eleven patients (16%) had significant QTc prolongation to >465 milliseconds after the infusion, with 3 (4%) to >500 milliseconds. There were 2 patients (2%) for whom the infusion was terminated early.
Conclusions:
IV sotalol was safe and effective for termination or improvement of tachyarrhythmias in 79% of pediatric patients and patients with congenital heart disease, including those with severely depressed cardiac function. The most common dose, for both acute and maintenance dosing, was 1 mg/kg over ~60 minutes with rare serious complications.




J Am Heart Assoc: 02 May 2022:e024375; epub ahead of print
Malloy-Walton LE, Von Bergen NH, Balaji S, Fischbach PS, ... Avari Silva JN, Saul JP
J Am Heart Assoc: 02 May 2022:e024375; epub ahead of print | PMID: 35491986
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Impact:
Abstract

Left Atrial Remodeling and Stroke in Patients With Sinus Rhythm and Normal Ejection Fraction: ARIC-NCS.

Bianco F, De Caterina R, Chandra A, Aquila I, ... Solomon SD, Chen LY

Background:
Age-related left atrial (LA) structural and functional abnormalities may be related to subclinical cerebral infarcts (SCIs) and stroke. We evaluated the association of 3-dimensional echocardiographic LA contractility parameters with SCIs and stroke across the spectrum of tertiles of age increment in elderly patients with sinus rhythm, normal ejection fraction, and no history of atrial fibrillation. Methods and Results We enrolled 407 participants (mean age, 76±8 years; 40% men) from ARIC-NCS (Atherosclerosis Risk in Communities Neurocognitive Study) undergoing a brain magnetic resonance imaging and 3-dimensional echocardiographic examinations in 2011 to 2013. The sample was analyzed among age tertiles and subgroups: no cerebral magnetic resonance imaging-detectable infarcts (n=315), magnetic resonance imaging-diagnosed SCIs (n=58), and clinically diagnosed stroke (n=34). The frequency of SCIs significantly increased over age tertiles (P trend 0.023). LA global longitudinal strain-a 3-dimensional echocardiographic index of LA reservoir function-and E/e\' divided by LA global longitudinal strain-an index of LA stiffness-worsened across age tertiles (P trend 0.014 and 0.001, respectively), and only in the categories of SCIs (P trend <0.001 and 0.045, respectively) and stroke (P trend 0.001 and 0.011, respectively). LA global longitudinal strain was negatively associated with increased odds of SCIs (P=0.036, P=0.008, and P=0.001, respectively) and strokes (P=0.043, P=0.015, and P=0.001, respectively) over age tertiles, with a significant interaction between age tertiles (interaction P=0.043 and P=0.010, respectively). E/e\' divided by LA global longitudinal strain was positively associated with the presence of SCIs (P=0.037, P=0.007, and P=0.001, respectively) and strokes (P=0.045, P=0.007, and P=0.003, respectively) over age tertiles, with a significant interaction only for SCIs (interaction P=0.040) and not for clinical stroke.
Conclusions:
In a large cohort study of elderly patients, among participants with sinus rhythm, normal ejection fraction, and no history of atrial fibrillation, measures of worse age-related LA reservoir function and stiffness are associated with higher odds of SCIs and stroke.




J Am Heart Assoc: 02 May 2022:e024292; epub ahead of print
Bianco F, De Caterina R, Chandra A, Aquila I, ... Solomon SD, Chen LY
J Am Heart Assoc: 02 May 2022:e024292; epub ahead of print | PMID: 35491988
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Impact:
Abstract

Combined Associations of Physical Activity and Particulate Matter With Subsequent Cardiovascular Disease Risk Among 5-Year Cancer Survivors.

Choi D, Choi S, Kim KH, Kim K, ... Son JS, Park SM

Background:
The combined associations of physical activity and particulate matter (PM) with subsequent cardiovascular disease (CVD) risk is yet unclear. Methods and Results The study population consisted of 18 846 cancer survivors who survived for at least 5 years after initial cancer diagnosis from the Korean National Health Insurance Service database. Average PM levels for 4 years were determined in administrative district areas, and moderate-to-vigorous physical activity (MVPA) information was acquired from health examination questionnaires. A multivariable Cox proportional hazards model was used to evaluate the risk for CVD. Among patients with low PM with particles ≤2.5 µm (PM2.5; (19.8-25.6 μg/m3) exposure, ≥5 times per week of MVPA was associated with lower CVD risk (adjusted hazard ratio [aHR], 0.77; 95% CI, 0.60-0.99) compared with 0 times per week of MVPA. Also, a higher level of MVPA frequency was associated with lower CVD risk (P for trend=0.028) among cancer survivors who were exposed to low PM2.5 levels. In contrast, ≥5 times per week of MVPA among patients with high PM2.5 (25.8-33.8 μg/m3) exposure was not associated with lower CVD risk (aHR, 0.98; 95% CI, 0.79-1.21). Compared with patients with low PM2.5 and MVPA ≥3 times per week, low PM2.5 and MVPA ≤2 times per week (aHR, 1.26; 95% CI, 1.03-1.55), high PM2.5 and MVPA ≥3 times per week (aHR, 1.34; 95% CI, 1.07-1.67), and high PM2.5 and MVPA ≤2 times per week (aHR, 1.38; 95% CI, 1.12-1.70) was associated with higher CVD risk.
Conclusions:
Cancer survivors who engaged in MVPA ≥5 times per week benefited from lower CVD risk upon low PM2.5 exposure. High levels of PM2.5 exposure may attenuate the risk-reducing effects of MVPA on the risk of CVD.




J Am Heart Assoc: 02 May 2022:e022806; epub ahead of print
Choi D, Choi S, Kim KH, Kim K, ... Son JS, Park SM
J Am Heart Assoc: 02 May 2022:e022806; epub ahead of print | PMID: 35491990
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Impact:
Abstract

Association Between the Acidemia, Lactic Acidosis, and Shock Severity With Outcomes in Patients With Cardiogenic Shock.

Jentzer JC, Schrage B, Patel PC, Kashani KB, ... Kirchhof P, Westermann D

Background:
Lactic acidosis is associated with mortality in patients with cardiogenic shock (CS). Elevated lactate levels and systemic acidemia (low blood pH) have both been proposed as drivers of death. We, therefore, analyzed the association of both high lactate concentrations and low blood pH with 30-day mortality in patients with CS. Methods and Results This was a 2-center historical cohort study of unselected patients with CS with available data for admission lactate level or blood pH. CS severity was graded using the Society for Cardiovascular Angiography and Intervention (SCAI) shock classification. All-cause survival at 30 days was analyzed using Kaplan-Meier curves and Cox proportional-hazards analysis. There were 1814 patients with CS (mean age, 67.3 years; 68.5% men); 51.8% had myocardial infarction and 53.0% had cardiac arrest. The distribution of SCAI shock stages was B, 10.8%; C, 30.7%; D, 38.1%; and E, 18.7%. In both cohorts, higher lactate or lower pH predicted a higher risk of adjusted 30-day mortality. Patients with a lactate ≥5 mmol/L or pH <7.2 were at increased risk of adjusted 30-day mortality; patients with both lactate ≥5 mmol/L and pH <7.2 had the highest risk of adjusted 30-day mortality. Patients in SCAI shock stages C, D, and E had higher 30-day mortality in each SCAI shock stage if they had lactate ≥5 mmol/L or pH <7.2, particularly if they met both criteria.
Conclusions:
Higher lactate and lower pH predict mortality in patients with cardiogenic shock beyond standard measures of shock severity. Severe lactic acidosis may serve as a risk modifier for the SCAI shock classification. Definitions of refractory or hemometabolic shock should include high lactate levels and low blood pH.




J Am Heart Assoc: 02 May 2022:e024932; epub ahead of print
Jentzer JC, Schrage B, Patel PC, Kashani KB, ... Kirchhof P, Westermann D
J Am Heart Assoc: 02 May 2022:e024932; epub ahead of print | PMID: 35491996
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Impact:
Abstract

Obesity, Galectin-3, and Incident Heart Failure: The ARIC Study.

Florido R, Kwak L, Echouffo-Tcheugui JB, Zhang S, ... Ballantyne C, Ndumele CE

Background:
Laboratory data suggest obesity is linked to myocardial inflammation and fibrosis, but clinical data are limited. We aimed to examine the association of obesity with galectin-3, a biomarker of cardiac inflammation and fibrosis, and the related implications for heart failure (HF) risk. Methods and Results We evaluated 8687 participants (mean age 63 years; 21% Black) at ARIC (Atherosclerosis Risk in Communities) Visit 4 (1996-1998) who were free of heart disease. We used adjusted logistic regression to estimate the association of body mass index (BMI) categories with elevated galectin-3 (≥75th sex-specific percentile) overall and across demographic subgroups, with tests for interaction. We used Cox proportional hazards models to assess the combined associations of galectin-3 and BMI with incident HF (through December 31, 2019). Higher BMI was associated with higher odds of elevated galectin-3 (odds ratio [OR], 2.32; 95% CI, 1.88-2.86) for severe obesity ([BMI ≥35 kg/m2] versus normal weight [BMI 18.5-<25 kg/m2]). There were stronger associations of BMI with elevated galectin-3 among women versus men and White versus Black participants (both P-for-interaction <0.05). Elevated galectin-3 was similarly associated with incident HF among people with and without obesity (HR, 1.49; 95% CI, 1.18-1.88; and HR, 1.71; 95% CI, 1.38-2.11, respectively). People with severe obesity and elevated galectin-3 had >4-fold higher risk of HF (HR, 4.19; 95% CI, 2.98-5.88) than those with normal weight and galectin-3 <25th percentile.
Conclusions:
Obesity is strongly associated with elevated galectin-3. Additionally, the combination of obesity and elevated galectin-3 is associated with marked HF risk, underscoring the importance of elucidating pathways linking obesity with cardiac inflammation and fibrosis.




J Am Heart Assoc: 02 May 2022:e023238; epub ahead of print
Florido R, Kwak L, Echouffo-Tcheugui JB, Zhang S, ... Ballantyne C, Ndumele CE
J Am Heart Assoc: 02 May 2022:e023238; epub ahead of print | PMID: 35491999
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Abstract

Sex-Related Differences in Clinical Features and In-Hospital Outcomes of Type B Acute Aortic Dissection: A Registry Study.

Takahashi T, Yoshino H, Akutsu K, Shimokawa T, ... Nagao K, Takayama M

Background:
The association between female sex and poor outcomes following surgery for type A acute aortic dissection has been reported; however, sex-related differences in clinical features and in-hospital outcomes of type B acute aortic dissection, including classic aortic dissection and intramural hematoma, remain to be elucidated. Methods and Results We studied 2372 patients with type B acute aortic dissection who were enrolled in the Tokyo Acute Aortic Super-Network Registry. There were fewer and older women than men (median age [interquartile range]: 76 years [66-84 years], n=695 versus 68 years [57-77 years], n=1677; P<0.001). Women presented to the aortic centers later than men. Women had a higher proportion of intramural hematoma (63.7% versus 53.7%, P<0.001), were medically managed more frequently (90.9% versus 86.3%, P=0.002), and had less end-organ malperfusion (2.4% versus 5.7%, P<0.001) and higher in-hospital mortality (5.3% versus 2.7%, P=0.002) than men. In multivariable analysis, age (per year, odds ratio [OR], 1.06 [95% CI, 1.03-1.08]; P<0.001), hyperlipidemia (OR, 2.09 [95% CI, 1.13-3.88]; P=0.019), painlessness (OR, 2.59 [95% CI, 1.14-5.89]; P=0.023), shock/hypotension (OR, 2.93 [95% CI, 1.21-7.11]; P=0.017), non-intramural hematoma (OR, 2.31 [95% CI, 1.32-4.05]; P=0.004), aortic rupture (OR, 26.6 [95% CI, 14.1-50.0]; P<0.001), and end-organ malperfusion (OR, 4.61 [95% CI, 2.11-10.1]; P<0.001) were associated with higher in-hospital mortality, but was not female sex (OR, 1.67 [95% CI, 0.96-2.91]; P=0.072).
Conclusions:
Women affected with type B acute aortic dissection were older and had more intramural hematoma, a lower incidence of end-organ malperfusion, and higher in-hospital mortality than men. However, female sex was not associated with in-hospital mortality after multivariable adjustment.




J Am Heart Assoc: 02 May 2022:e024149; epub ahead of print
Takahashi T, Yoshino H, Akutsu K, Shimokawa T, ... Nagao K, Takayama M
J Am Heart Assoc: 02 May 2022:e024149; epub ahead of print | PMID: 35492000
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Impact:
Abstract

Fallacy of Median Door-to-ECG Time: Hidden Opportunities for STEMI Screening Improvement.

Yiadom MYAB, Gong W, Patterson BW, Baugh CW, ... Ulintz A, Liu D

Background:
ST-segment elevation myocardial infarction (STEMI) guidelines recommend screening arriving emergency department (ED) patients for an early ECG in those with symptoms concerning for myocardial ischemia. Process measures target median door-to-ECG (D2E) time of 10 minutes. Methods and Results This 3-year descriptive retrospective cohort study, including 676 ED-diagnosed patients with STEMI from 10 geographically diverse facilities across the United States, examines an alternative approach to quantifying performance: proportion of patients meeting the goal of D2E≤10 minutes. We also identified characteristics associated with D2E>10 minutes and estimated the proportion of patients with screening ECG occurring during intake, triage, and main ED care periods. We found overall median D2E was 7 minutes (IQR:4-16; range: 0-1407 minutes; range of ED medians: 5-11 minutes). Proportion of patients with D2E>10 minutes was 37.9% (ED range: 21.5%-57.1%). Patients with D2E>10 minutes, compared to those with D2E≤10 minutes, were more likely female (32.8% versus 22.6%, P=0.005), Black (23.4% versus 12.4%, P=0.005), non-English speaking (24.6% versus 19.5%, P=0.032), diabetic (40.2% versus 30.2%, P=0.010), and less frequently reported chest pain (63.3% versus 87.4%, P<0.001). ECGs were performed during ED intake in 62.1% of visits, ED triage in 25.3%, and main ED care in 12.6%.
Conclusions:
Examining D2E>10 minutes can identify opportunities to improve care for more ED patients with STEMI. Our findings suggest sex, race, language, and diabetes are associated with STEMI diagnostic delays. Moving the acquisition of ECGs completed during triage to intake could achieve the D2E≤10 minutes goal for 87.4% of ED patients with STEMI. Sophisticated screening, accounting for differential risk and diversity in STEMI presentations, may further improve timely detection.




J Am Heart Assoc: 02 May 2022:e024067; epub ahead of print
Yiadom MYAB, Gong W, Patterson BW, Baugh CW, ... Ulintz A, Liu D
J Am Heart Assoc: 02 May 2022:e024067; epub ahead of print | PMID: 35492001
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Impact:
Abstract

Age-Related Associations of Low-Density Lipoprotein Cholesterol and Atherosclerotic Cardiovascular Disease: A Nationwide Population-Based Cohort Study.

Jung HN, Kim MJ, Kim HS, Lee WJ, ... Kim YJ, Jung CH

Background:
The relationship between low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD) according to age remains undetermined. Thus, this study aimed to investigate the age-related association of LDL-C and ASCVD. Methods and Results Data from the Korean NHIS-HEALS (National Health Insurance Service-National Health Screening Cohort) were analyzed. Individuals previously diagnosed with cardiovascular disease or taking lipid-lowering drugs were excluded. Age-specific association between LDL-C and ASCVD was calculated using adjusted Cox proportional hazards models. During a median follow-up of 6.44 years for 285 119 adults, ASCVD developed in 8996 (3.2%). All age groups showed positive associations between LDL-C and ASCVD risk, mostly with statistical significance from LDL-C of 160 mg/dL onward. ASCVD risk did not differ significantly between the age groups (P for interaction=0.489). Correspondingly, subgroup analysis in type 2 diabetes exhibited no difference in the age-specific association of LDL-C and ASCVD (P for interaction=0.784).
Conclusions:
The study demonstrated that people aged ≥75 years with higher LDL-C at baseline still presented increased ASCVD risk, which was not significantly different from the younger groups. These findings support the importance of managing LDL-C for the prevention of primary ASCVD in the growing elderly population.




J Am Heart Assoc: 02 May 2022:e024637; epub ahead of print
Jung HN, Kim MJ, Kim HS, Lee WJ, ... Kim YJ, Jung CH
J Am Heart Assoc: 02 May 2022:e024637; epub ahead of print | PMID: 35492003
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Impact:
Abstract

Implementation of an Appointment-Based Cardiac Rehabilitation Approach: A Single-Center Experience.

Wright CX, Fournier S, Deng Y, Meng C, ... Oen-Hsiao JM, Dreyer RP

Background:
There has been a focus on alternative cardiac rehabilitation (CR) delivery models aimed at improving CR adherence and completion. We examined pre- and post-CR health outcomes, reasons for discharge, and predictors of completion using a patient-driven appointment-based CR approach that uses center-scheduled class start times. Methods and Results Data were used from an urban single-center CR program at Yale New Haven Health (2012-2017) that enrolled 2135 patients. We evaluated pre- and post-CR outcomes (12 weeks) using paired t tests and used a multivariable logistic regression model to examine predictors of CR completion (≥36 sessions) for the overall cardiovascular disease population. The mean age of participants was 65±12 years, 27.9% were women, and 5.1% were Black patients, and patients completed a median of 30 of 36 sessions. Patients achieved significant improvements in health outcomes, including across age and sex subgroups. The primary reason for discharge was completion of all 36 sessions of CR (46.4%). The final logistic regression model contained 12 predictors: age, sex, Black race, marital status, employment, number of physician-reported risk factors, dietary fat intake >30%, obesity, lack of exercise, benign prostatic hyperplasia, and self-reported stress and physical activity.
Conclusions:
We demonstrated that patients participating in an appointment-based CR program achieved significant improvements in health outcomes and across sex/age subgroups. In addition, older individuals were more likely to complete CR. An appointment-based approach could be a viable alternative CR method to aid in optimizing the dose-response benefit of CR for patients with cardiovascular disease.




J Am Heart Assoc: 02 May 2022:e024066; epub ahead of print
Wright CX, Fournier S, Deng Y, Meng C, ... Oen-Hsiao JM, Dreyer RP
J Am Heart Assoc: 02 May 2022:e024066; epub ahead of print | PMID: 35499969
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Impact:
Abstract

Change of Heart: The Underexplored Role of Plaque Hemorrhage in the Evaluation of Stroke of Undetermined Etiology.

Holmes DR, Alkhouli MA, Klaas JP, Brinjikji W, ... Lanzino G, Benson JC
In the evaluation of embolic strokes of undetermined source, great emphasis is often placed on cardiovascular disease, namely on atrial fibrillation. Other pathophysiologic mechanisms, however, may also be involved. Carotid artery intraplaque hemorrhage (IPH)-the presence of blood components within an atheromatous plaque-has become increasingly recognized as a possible etiologic mechanism in some cryptogenic strokes. IPH is a marker of plaque instability and is associated with ipsilateral neurologic ischemic events, even in nonstenotic carotid plaques. As recognition of carotid IPH as an etiology of embolic strokes has grown, so too has the complexity with which such patients are evaluated and treated, particularly because overlaps exist in the risk factors for atrial fibrillation and IPH. In this article, we review what is currently known about carotid IPH and how this clinical entity should be approached in the context of the evaluation of embolic strokes of undetermined source.



J Am Heart Assoc: 27 Apr 2022:e025323; epub ahead of print
Holmes DR, Alkhouli MA, Klaas JP, Brinjikji W, ... Lanzino G, Benson JC
J Am Heart Assoc: 27 Apr 2022:e025323; epub ahead of print | PMID: 35475334
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Impact:
Abstract

Association of Exposure to Abuse, Nurture, and Household Organization in Childhood With 4 Cardiovascular Disease Risks Factors Among Participants in the CARDIA Study.

Aguayo L, Chirinos DA, Heard-Garris N, Wong M, ... Seeman T, Kershaw KN

Background:
We investigated associations of childhood abuse with 4 cardiovascular disease risk factors in adulthood, and whether exposure to nurturing and household organization in childhood mitigated these associations. Methods and Results The CARDIA (Coronary Artery Risk Development in Young Adults) study (baseline examination, 1985-1986) was used to examine associations of childhood exposures (measured retrospectively at the year 15 examination) with incident obesity, type 2 diabetes, hypertension, and hyperlipidemia (assessed from baseline to year 30). Race- and sex-stratified Cox proportional hazards models were used to examine associations of exposure to childhood abuse with incident cardiovascular disease risk factors. Interaction terms between exposure to abuse and exposure to nurturing relationship and household organization were included to test for effect modifications. Exposure to occasional/frequent abuse (versus no abuse) was associated with incident type 2 diabetes among White men (hazard ratio [HR], 1.81; 95% CI, 1.06-3.08). Exposure to low versus no abuse was associated with incident hyperlipidemia among White men (HR, 1.35; 95% CI, 1.09-1.67) and White women (HR, 1.26; 95% CI, 1.01-1.56). Risks of incident hyperlipidemia were higher for White women who experienced abuse and lived in dysfunctional households (HR, 3.61; 95% CI, 1.62-8.05) or households with low levels of organization (HR, 2.05; 95% CI, 1.25-3.36) compared with White women who experienced abuse but lived in well-organized households (HR, 0.66; 95% CI, 0.41-1.06). Similar patterns were seen for Black men who lived in dysfunctional households (HR, 3.62; 95% CI, 1.29-10.12) or households with low organization (HR, 2.01; 95% CI, 1.08-3.72).
Conclusions:
We identified race- and sex-specific associations of childhood exposures with incident cardiovascular disease risk factors. The associations of household organization and dysfunction with cardiovascular disease risks merits further investigation.




J Am Heart Assoc: 27 Apr 2022:e023244; epub ahead of print
Aguayo L, Chirinos DA, Heard-Garris N, Wong M, ... Seeman T, Kershaw KN
J Am Heart Assoc: 27 Apr 2022:e023244; epub ahead of print | PMID: 35475340
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Impact:
Abstract

National Trends in Use of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists by Cardiologists and Other Specialties, 2015 to 2020.

Adhikari R, Jha K, Dardari Z, Heyward J, ... Alexander GC, Blaha MJ

Background:
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) mitigate cardiovascular risk in individuals with type 2 diabetes, but most eligible patients do not receive them. We characterized temporal trends in SGLT2i and GLP-1RA use by cardiologists compared with other groups of clinicians. Methods and Results We conducted a descriptive analysis of serial, cross-sectional data derived from IQVIA\'s National Prescription Audit, a comprehensive audit capturing ≈90% of US retail prescription dispensing and projected to population-level data, to estimate monthly SGLT2is and GLP-1RAs dispensed from January 2015 to December 2020, stratified by prescriber specialty and molecule. We also used the American Medical Association\'s Physician Masterfile to calculate average annual SGLT2is and GLP-1RAs dispensed per physician. Between January 2015 and December 2020, a total of 63.2 million SGLT2i and 63.4 million GLP-1RA prescriptions were dispensed in the United States. Monthly prescriptions from cardiologists increased 12-fold for SGLT2is (from 2228 to 25 815) and 4-fold for GLP-1RAs (from 1927 to 6981). Nonetheless, cardiologists represented only 1.5% of SGLT2i prescriptions and 0.4% of GLP-1RA prescriptions in 2020, while total use was predominated by primary care physicians/internists (57% of 2020 SGLT2is and 52% of GLP-1RAs). Endocrinologists led in terms of prescriptions dispensed per physician in 2020 (272 SGLT2is and 405 GLP-1RAs). Cardiologists, but not noncardiologists, increasingly used SGLT2is over GLP-1RAs, with accelerated uptake of empagliflozin and dapagliflozin coinciding with their landmark cardiovascular outcomes trials and subsequent US Food and Drug Administration label expansions.
Conclusions:
While use of SGLT2is and GLP-1RAs by cardiologists in the United States increased substantially over a 6-year period, cardiologists still account for a very small proportion of all use, contributing to marked undertreatment of individuals with type 2 diabetes at high cardiovascular risk.




J Am Heart Assoc: 27 Apr 2022:e023811; epub ahead of print
Adhikari R, Jha K, Dardari Z, Heyward J, ... Alexander GC, Blaha MJ
J Am Heart Assoc: 27 Apr 2022:e023811; epub ahead of print | PMID: 35475341
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Impact:
Abstract

Relationship Between Image Quality and Bias in 3D Echocardiographic Measures: Data From the SABRE (Southall and Brent Revisited) Study.

Al Saikhan L, Park C, Tillin T, Lloyd G, ... Chaturvedi N, Hughes AD

Background:
Image-quality (IQ) compromises left ventricle assessment by 3-dimensional echocardiography (3DE). Sicker/frailer patients often have suboptimal IQ, and therefore observed associations may be biased by IQ. We investigated its effect in an observational study of older people and when IQ was modified experimentally in healthy volunteers. Methods and Results 3DE feasibility by IQ was assessed in 1294 individuals who attended the second wave of the Southall and Brent Revisited study and was compared with 2-dimensional (2D)-echocardiography feasibility in 147 individuals. Upon successful analysis, means of ejection fraction (3D-EF) and global longitudinal strain (3D-GLS) (plus 2D-EF) were compared in individuals with poor versus good IQ. In 2 studies of healthy participants, 3DE-IQ was impaired by (1) intentionally poor echocardiographic technique, and (2) use of a sheet of ultrasound-attenuating material (neoprene rubber; 2-4 mm). The feasibility was 41% (529/1294) for 3DE versus 61% (89/147) for 2D-EF, P<0.0001. Among acceptable images (n=529), good IQ by the 2015 American Society of Echocardiography/European Association of Cardiovascular Imaging criteria was 33.6% (178/529) and 71.3% (377/529) for 3D-EF and 3D-GLS, respectively. Individuals with poor IQ had lower 3D-EF and 3D-GLS (absolute) than those with good IQ (3D-EF: 52.8±6.0% versus 55.7±5.7%, Mean-Δ -2.9 [-3.9, 1.8]; 3D-GLS: 18.6±3.2% versus 19.2±2.9%, Mean-Δ -0.6 [-1.1, 0.0]). In 2 experimental models of poor IQ (n=36 for both), mean differences were (-2.6 to -3.2) for 3D-EF and (-1.2 to -2.0) for 3D-GLS. Similar findings were found for other 3DE left ventricle volumes and strain parameters.
Conclusions:
3DE parameters have low feasibility and values are systematically lower in individuals with poor IQ. Although 3D-EF and 3D-GLS have potential advantages over conventional echocardiography, further technical improvements are required to improve the utility of 3DE in clinical practice.




J Am Heart Assoc: 27 Apr 2022:e019183; epub ahead of print
Al Saikhan L, Park C, Tillin T, Lloyd G, ... Chaturvedi N, Hughes AD
J Am Heart Assoc: 27 Apr 2022:e019183; epub ahead of print | PMID: 35475343
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Impact:
Abstract

Perioperative Cardiometabolic Targets and Coronary Artery Bypass Surgery Mortality in Patients With Diabetes.

Skendelas JP, Phan DK, Friedmann P, Rodriguez CJ, ... Forest SJ, Slipczuk L

Background:
Coronary artery bypass graft (CABG) surgery represents the preferred revascularization strategy for most patients with diabetes and multivessel disease. We aimed to evaluate the role of optimized, perioperative cardiometabolic targets on long-term survival in patients who underwent CABG. Methods and Results Single-institution retrospective study was conducted in patients with diabetes who underwent CABG between January 2010 and June 2018. Demographic, surgical, and cardiometabolic determinants were identified during the perioperative period. Clinical characteristics and longitudinal survival outcomes data were obtained. A total of 1534 patients with CABG were considered for analysis and 1273 met inclusion criteria. The mean age of patients was 63.3 years (95% CI, 62.7-63.8 years), and most were men (65%) and Hispanic or Latino (47%). Comorbidities included hypertension (95%) and dyslipidemia (88%). In total, 490 patients (52%) had a low-density lipoprotein cholesterol level >70 mg/dL. Furthermore, 390 patients (31%) had uncontrolled systolic blood pressure >130 mm Hg. Last, only 386 patients (29%) had a hemoglobin A1c level between 6% and 7%. At 5 years, 121 patients (10%) died. Failure to achieve goal systolic blood pressure was associated with all-cause (hazard ratio [HR], 1.573; 95% CI, 1.048-2.362 [P=0.029]) and cardiovascular (HR, 2.023; 95% CI, 1.196-3.422 [P=0.009]) mortality at 5 years post-CABG. In contrast, prescription of a statin during the perioperative interval demonstrated a protective effect for all-cause (HR, 0.484; 95% CI, 0.286-0.819 [P=0.007]) and cardiovascular (HR, 0.459; 95% CI, 0.229-0.920 [P=0.028]) mortality. There was no association between achievement of low-density lipoprotein cholesterol, triglycerides, non-high-density lipoprotein cholesterol, or hemoglobin A1c level goals and mortality risk at 5 years.
Conclusions:
Among patients with diabetes, blood pressure control and statin therapy were the most important perioperative cardiometabolic survival determinants 5 years after CABG.




J Am Heart Assoc: 27 Apr 2022:e023558; epub ahead of print
Skendelas JP, Phan DK, Friedmann P, Rodriguez CJ, ... Forest SJ, Slipczuk L
J Am Heart Assoc: 27 Apr 2022:e023558; epub ahead of print | PMID: 35475344
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Impact:
Abstract

Event Rates and Risk Factors for Recurrent Cardiovascular Events and Mortality in a Contemporary Post Acute Coronary Syndrome Population Representing 239 234 Patients During 2005 to 2018 in the United States.

Steen DL, Khan I, Andrade K, Koumas A, Giugliano RP

Background:
Patients with acute coronary syndrome (ACS) are recognized by guidelines as remaining at high risk for adverse outcomes. Evidence from contemporary, representative ACS populations in a clinical practice setting is necessary to identify subgroups and strategies for improving patient outcomes. We aimed to describe event rates and risk factors in an ACS population over prolonged follow-up for cardiovascular end points. Methods and Results We identified 239 234 patients in the Optum Research Database (57.2% men; mean [standard deviation] age, 69.2 [12.2] years) with evidence of an ACS hospitalization (index ACS) during January 1, 2005 through December 30, 2018. Subgroups were based on index ACS event (myocardial infarction/unstable angina and revascularization status) and the Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention. The 5-year event rate for the primary end point representing nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular death was 33.4% (95% CI, 33.1%-33.7%; P<0.001). The risk of experiencing the primary end point was ≈6-fold higher immediately after discharge (≈40.9% annualized risk) as compared with the period 1+ years after hospitalization (≈6.4% annualized risk). Among subgroups, the 5-year primary end point event rate was highest for myocardial infarction without revascularization and a Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention ≥4, at 47.9% (95% CI, 47.3%-48.4%; P<0.001) and 56.7% (95% CI, 55.9%-57.4%; P<0.001), respectively.
Conclusions:
Patients with ACS remain at very high risk of experiencing recurrent cardiovascular events, particularly early after discharge, with identifiable subgroups at multifold higher risk of specific clinical end points.




J Am Heart Assoc: 27 Apr 2022:e022198; epub ahead of print
Steen DL, Khan I, Andrade K, Koumas A, Giugliano RP
J Am Heart Assoc: 27 Apr 2022:e022198; epub ahead of print | PMID: 35475346
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Impact:
Abstract

Age-Dependent Relationship of Hypertension Subtypes With Incident Heart Failure.

Suzuki Y, Kaneko H, Yano Y, Okada A, ... Yasunaga H, Komuro I

Background:
The prevalence of hypertension subtypes changes with age. However, little is known regarding the age-dependent association of hypertension subtypes with incident heart failure (HF). Methods and Results We conducted an observational cohort study including 2 612 570 people (mean age, 44.0 years; 55.0% men). No participants were taking blood pressure-lowering medications or had a known history of cardiovascular disease. Participants were categorized as aged 20 to 49 years (n=1 825 756), 50 to 59 years (n=571 574), or 60 to 75 years (n=215 240). We defined stage 1 hypertension as systolic blood pressure (SBP) 130 to 139 mm Hg or diastolic blood pressure (DBP) 80 to 89 mm Hg and stage 2 hypertension as SBP ≥140 mm Hg or DBP ≥90 mm Hg. Among participants with stage 2 hypertension, isolated diastolic hypertension was defined as SBP <140 mm Hg and DBP ≥90 mm Hg, isolated systolic hypertension as SBP ≥140 mm Hg and DBP <90 mm Hg, and systolic diastolic hypertension as SBP ≥140 mm Hg and DBP ≥90 mm Hg. During a mean follow-up of 1205±934 days, 43 415 HF, 4807 myocardial infarction, 45 365 angina pectoris, 22 179 stroke, and 10 420 atrial fibrillation events occurred. Although the incidence of HF and other cardiovascular disease events increased with age, hazard ratios and relative risk reductions of each hypertension subtype for HF decreased with age. An age-dependent relationship between hypertension subtypes and incident HF was similarly observed in both men and women.
Conclusions:
The contribution of isolated diastolic hypertension, isolated systolic hypertension, and systolic diastolic hypertension to the development of HF and other cardiovascular disease events was attenuated with age, suggesting that preventive efforts for blood pressure control could provide a greater benefit in younger individuals.




J Am Heart Assoc: 27 Apr 2022:e025406; epub ahead of print
Suzuki Y, Kaneko H, Yano Y, Okada A, ... Yasunaga H, Komuro I
J Am Heart Assoc: 27 Apr 2022:e025406; epub ahead of print | PMID: 35475350
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Impact:
Abstract

Mortality in Pulmonary Arterial Hypertension in the Modern Era: Early Insights From the Pulmonary Hypertension Association Registry.

Chang KY, Duval S, Badesch DB, Bull TM, ... Thenappan T, PHAR Investigators *

Background:
Current mortality data for pulmonary arterial hypertension (PAH) in the United States are based on registries that enrolled patients prior to 2010. We sought to determine mortality in PAH in the modern era using the PHAR (Pulmonary Hypertension Association Registry). Methods and Results We identified all adult patients with PAH enrolled in the PHAR between September 2015 and September 2020 (N=935). We used Kaplan-Meier survival analysis and Cox proportional hazards models to assess mortality at 1, 2, and 3 years. Patients were stratified based on disease severity by 3 validated risk scores. In treatment-naïve patients, we compared survival based on initial treatment strategy. The median age was 56 years (44-68 years), and 76% were women. Of the 935 patients, 483 (52%) were ≤6 months from PAH diagnosis. There were 121 deaths (12.9%) during a median follow-up time of 489 days (281-812 days). The 1-, 2-, and 3-year mortality was 8% (95% CI, 6%-10%), 16% (95% CI, 13%-19%), and 21% (95% CI, 17%-25%), respectively. When stratified into low-, intermediate-, and high-risk PAH, the mortality at 1, 2, and 3 years was 1%, 4% to 6%, and 7% to 11% for low risk; 7% to 8%, 11% to 16%, and 18% to 20% for intermediate risk; and 12% to 19%, 22% to 38%, and 28% to 55% for high risk, respectively. In treatment-naïve patients, initial combination therapy was associated with better 1-year survival (adjusted hazard ratio, 0.43 [95% CI, 0.19-0.95]; P=0.037).
Conclusions:
Mortality in the intermediate- and high-risk patients with PAH remains unacceptably high in the PHAR, suggesting the importance for early diagnosis, aggressive use of available therapies, and the need for better therapeutics.




J Am Heart Assoc: 27 Apr 2022:e024969; epub ahead of print
Chang KY, Duval S, Badesch DB, Bull TM, ... Thenappan T, PHAR Investigators *
J Am Heart Assoc: 27 Apr 2022:e024969; epub ahead of print | PMID: 35475351
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Impact:
Abstract

Serial Assessment of Right Ventricular Deformation in Patients With Hypoplastic Left Heart Syndrome: A Cardiovascular Magnetic Resonance Feature Tracking Study.

Kanngiesser LM, Freitag-Wolf S, Boroni Grazioli S, Gabbert DD, ... Uebing AS, Voges I

Background:
As right ventricular dysfunction is a major cause of adverse outcome in patients with hypoplastic left heart syndrome, the aim was to assess right ventricular function and deformation after Fontan completion by performing 2-dimensional cardiovascular magnetic resonance feature tracking in serial cardiovascular magnetic resonance studies. Methods and Results Cardiovascular magnetic resonance examinations of 108 patients with hypoplastic left heart syndrome (female: 31) were analyzed. Short-axis cine images were used for right ventricular volumetry. Two-dimensional cardiovascular magnetic resonance feature tracking was performed using long-axis and short-axis cine images to measure myocardial global longitudinal, circumferential, and radial strain. All patients had at least 2 cardiovascular magnetic resonance examinations after Fontan completion and 41 patients had 3 examinations. Global strain values and right ventricular ejection fraction decreased from the first to the third examination with a significant decline in global longitudinal strain from the first examination to the second examination (median, first, and third quartile: -18.8%, [-20.5;-16.5] versus -16.9%, [-19.3;-14.7]) and from the first to the third examination in 41 patients (-18.6%, [-20.9;-15.7] versus -15.8%, [-18.7;-12.6]; P-values <0.004). Right ventricular ejection fraction decreased significantly from the first to the third examination (55.4%, [49.8;59.3] versus 50.2%, [45.0;55.9]; P<0.002) and from the second to the third examination (53.8%, [47.2;58.7] versus 50.2%, [45.0;55.9]; P<0.0002).
Conclusions:
Serial assessment of cardiovascular magnetic resonance studies in patients with hypoplastic left heart syndrome after Fontan completion demonstrates a significant reduction in global strain values and right ventricular ejection fraction at follow-up. The significant reduction in global longitudinal strain between the first 2 examinations with non-significant changes in right ventricular ejection fraction suggest that global longitudinal strain measured by 2-dimensional cardiovascular magnetic resonance feature tracking might be a superior technique for the detection of changes in myocardial function.




J Am Heart Assoc: 27 Apr 2022:e025332; epub ahead of print
Kanngiesser LM, Freitag-Wolf S, Boroni Grazioli S, Gabbert DD, ... Uebing AS, Voges I
J Am Heart Assoc: 27 Apr 2022:e025332; epub ahead of print | PMID: 35475354
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Impact:
Abstract

Yield of Echocardiography in Ischemic Stroke and Patients With Transient Ischemic Attack With Established Indications for Long-Term Direct Oral Anticoagulant Therapy: A Cross-Sectional Diagnostic Cohort Study.

Meinel TR, Brignoli K, Kielkopf M, Clenin L, ... Buffle E, Jung S

Background:
We aimed to determine the diagnostic yield of transthoracic (TTE) and transesophageal echocardiography (TEE) in patients with ischemic stroke and transient ischemic attack with established indications for direct oral anticoagulants before the index event. Methods and Results This was a retrospective cohort study of consecutive patients with preceding established indications for long-term therapeutic direct oral anticoagulants presenting to a single comprehensive stroke center with ischemic stroke or transient ischemic attack. Choice of echocardiography modality was based on expert recommendations. The primary outcome was a composite of prespecified management-relevant high-risk findings adjudicated by an expert panel, based on TTE and TEE reports according to evidence-based recommendations. Explorative analyses were performed to identify biomarkers associated with the primary outcome. Of 424 patients included (median [interquartile range] age, 78 [70-84] years; 175 [41%] women; National Institutes of Health Stroke Scale, 4 [1-12]; 67% atrial fibrillation), 292 (69%) underwent echocardiography, while 132 (31%) did not. Modality was TTE in 191 (45%) and TEE in 101 (24%). Median time from index event to echocardiography was 2 (1-3) days. TTE identified 26 of 191 (14%) patients with 35 management-relevant pathologies. TEE identified 16 of 101(16%) patients with 20 management-relevant pathologies. Most management-relevant findings represented indicated coronary artery disease and valvular pathologies. In a further 3 of 191 (2%) patients with TTE and 4 of 101 (4%) patients with TEE, other relevant findings were identified. Variables associated with management-relevant high-risk pathologies included more severe stroke, diabetes, and laboratory biomarkers (NT-proBNP [N-terminal pro-B-type natriuretic peptide], C-reactive protein, d-dimer, and troponin levels).
Conclusions:
In patients with established indications for long-term direct oral anticoagulant therapy and stroke who received echocardiography, both TTE and TEE identified a relevant and similar proportion of management-relevant high-risk pathologies and predictive biomarkers could help to guide diagnostic workup in such patients.




J Am Heart Assoc: 27 Apr 2022:e024989; epub ahead of print
Meinel TR, Brignoli K, Kielkopf M, Clenin L, ... Buffle E, Jung S
J Am Heart Assoc: 27 Apr 2022:e024989; epub ahead of print | PMID: 35475357
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Impact:
Abstract

Clinical Relevance of Ischemia with Nonobstructive Coronary Arteries According to Coronary Microvascular Dysfunction.

Lee SH, Shin D, Lee JM, van de Hoef TP, ... Piek JJ, ILIAS Registry Investigators †

Background:
In the absence of obstructive coronary stenoses, abnormality of noninvasive stress tests (NIT) in patients with chronic coronary syndromes may indicate myocardial ischemia of nonobstructive coronary arteries (INOCA). The differential prognosis of INOCA according to the presence of coronary microvascular dysfunction (CMD) and incremental prognostic value of CMD with intracoronary physiologic assessment on top of NIT information remains unknown. Methods and Results From the international multicenter registry of intracoronary physiologic assessment (ILIAS [Inclusive Invasive Physiological Assessment in Angina Syndromes] registry, N=2322), stable patients with NIT and nonobstructive coronary stenoses with fractional flow reserve >0.80 were selected. INOCA was diagnosed when patients showed positive NIT results. CMD was defined as coronary flow reserve ≤2.5. According to the presence of INOCA and CMD, patients were classified into 4 groups: group 1 (no INOCA nor CMD, n=116); group 2 (only CMD, n=90); group 3 (only INOCA, n=41); and group 4 (both INOCA and CMD, n=40). The primary outcome was major adverse cardiovascular events, a composite of all-cause death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 5 years. Among 287 patients with nonobstructive coronary stenoses (fractional flow reserve=0.91±0.06), 81 patients (38.2%) were diagnosed with INOCA based on positive NIT. By intracoronary physiologic assessment, 130 patients (45.3%) had CMD. Regardless of the presence of INOCA, patients with CMD showed a significantly lower coronary flow reserve and higher hyperemic microvascular resistance compared with patients without CMD (P<0.001 for all). The cumulative incidence of major adverse cardiovascular events at 5 years were 7.4%, 21.3%, 7.7%, and 34.4% in groups 1 to 4. By documenting CMD (groups 2 and 4), intracoronary physiologic assessment identified patients at a significantly higher risk of major adverse cardiovascular events at 5 years compared with group 1 (group 2: adjusted hazard ratio [HRadjusted], 2.88; 95% CI, 1.52-7.19; P=0.024; group 4: HRadjusted, 4.00; 95% CI, 1.41-11.35; P=0.009).
Conclusions:
In stable patients with nonobstructive coronary stenoses, a diagnosis of INOCA based only on abnormal NIT did not identify patients with higher risk of long-term cardiovascular events. Incorporating intracoronary physiologic assessment to NIT information in patients with nonobstructive disease allowed identification of patient subgroups with up to 4-fold difference in long-term cardiovascular events. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04485234.




J Am Heart Assoc: 27 Apr 2022:e025171; epub ahead of print
Lee SH, Shin D, Lee JM, van de Hoef TP, ... Piek JJ, ILIAS Registry Investigators †
J Am Heart Assoc: 27 Apr 2022:e025171; epub ahead of print | PMID: 35475358
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Impact:
Abstract

Comparison of Multisystem Inflammatory Syndrome in Children-Related Myocarditis, Classic Viral Myocarditis, and COVID-19 Vaccine-Related Myocarditis in Children.

Patel T, Kelleman M, West Z, Peter A, ... Butto A, Oster ME

Background:
Although rare, classic viral myocarditis in the pediatric population is a disease that carries significant morbidity and mortality. Since 2020, myocarditis has been a common component of multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection. In 2021, myocarditis related to mRNA COVID-19 vaccines was recognized as a rare adverse event. This study aims to compare classic, MIS-C, and COVID-19 vaccine-related myocarditis with regard to clinical presentation, course, and outcomes. Methods and Results In this retrospective cohort study, we compared patients aged <21 years hospitalized at our institution with classic viral myocarditis from 2015 to 2019, MIS-C myocarditis from March 2020 to February 2021, and vaccine-related myocarditis from May 2021 to June 2021. Of 201 total participants, 43 patients had classic myocarditis, 149 had MIS-C myocarditis, and 9 had vaccine-related myocarditis. At presentation, ejection fraction was lowest for those with classic myocarditis, with ejection fraction <55% present in 58% of patients. Nearly all patients with MIS-C myocarditis (n=139, 93%) and all patients with vaccine-related myocarditis (n=9, 100%) had normal left ventricular ejection fraction at the time of discharge compared with 70% (n=30) of the classic myocarditis group (P<0.001). At 3 months after discharge, of the 21 children discharged with depressed ejection fraction, none of the 10 children with MIS-C myocarditis had residual dysfunction compared with 3 of the 11 (27%) patients in the classic myocarditis group.
Conclusions:
Compared with classic myocarditis, those with MIS-C myocarditis had better clinical outcomes, including rapid recovery of cardiac function. Patients with vaccine-related myocarditis had prompt resolution of symptoms and improvement of cardiac function.




J Am Heart Assoc: 27 Apr 2022:e024393; epub ahead of print
Patel T, Kelleman M, West Z, Peter A, ... Butto A, Oster ME
J Am Heart Assoc: 27 Apr 2022:e024393; epub ahead of print | PMID: 35475362
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Impact:
Abstract

How Do Lipoprotein(a) Concentrations Affect Clinical Outcomes for Patients With Stable Coronary Artery Disease Who Underwent Different Dual Antiplatelet Therapy After Percutaneous Coronary Intervention?

Cui K, Yin D, Zhu C, Song W, ... Feng L, Dou K

Background:
Lp(a) (lipoprotein[a]) plays an important role in predicting cardiovascular events in patients with coronary artery disease through its proatherogenic and prothrombotic effects. We hypothesized that prolonged dual antiplatelet therapy (DAPT) might be beneficial for patients undergoing percutaneous coronary intervention who had elevated Lp(a) levels. This study aimed to evaluate the effect of Lp(a) on the efficacy and safety of prolonged DAPT versus shortened DAPT in stable patients with coronary artery disease who were treated with a drug-eluting stent. Methods and Results We selected 3201 stable patients with CAD from the prospective Fuwai Percutaneous Coronary Intervention Registry, of which 2124 patients had Lp(a) ≤30 mg/dL, and 1077 patients had Lp(a) >30 mg/dL. Patients were divided into 4 groups according to Lp(a) levels and the duration of DAPT therapy (≤1 year versus >1 year). The primary end point was major adverse cardiovascular and cerebrovascular event, defined as a composite of all-cause death, myocardial infarction, or stroke. The median follow-up time was 2.5 years. Among patients with elevated Lp(a) levels, DAPT >1 year presented lower risk of major adverse cardiovascular and cerebrovascular event and definite/probable stent thrombosis compared with DAPT ≤1 year. In contrast, in patients with normal Lp(a) levels, the risks of major adverse cardiovascular and cerebrovascular event and definite/probable stent thrombosis were not significantly different between the DAPT >1 year and DAPT ≤1 year groups. Prolonged DAPT had 2.4-times higher risk of clinically relevant bleeding than shortened DAPT in patients with normal Lp(a) levels, although without statistical difference.
Conclusions:
In stable patients with coronary artery disease, who underwent percutaneous coronary intervention with a drug-eluting stent, prolonged DAPT was associated with reduced risk of cardiovascular events among those with elevated Lp(a) levels, whereas it did not show statistically significant evidence of benefit for reducing ischemic events and tended to increase clinically relevant bleeding among those with normal Lp(a) levels.




J Am Heart Assoc: 27 Apr 2022:e023578; epub ahead of print
Cui K, Yin D, Zhu C, Song W, ... Feng L, Dou K
J Am Heart Assoc: 27 Apr 2022:e023578; epub ahead of print | PMID: 35475627
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Impact:
Abstract

Ambient Air Pollution and Kawasaki Disease in Korean Children: A Study of the National Health Insurance Claim Data.

Kwon D, Choe YJ, Kim SY, Chun BC, Choe SA

Background:
Kawasaki disease (KD) is a systemic vasculitis of unknown etiology that primarily affects children under 5 years of age. Some researchers suggested a potential triggering effect of air pollution on KD, but the findings are inconsistent and limited by small sample size. We investigated the association between ambient air pollution and KD among the population of South Korea younger than 5 years using the National Health Insurance claim data between 2007 and 2019. Methods and Results We obtained the data regarding particulate matter ≤10 or 2.5 µm in diameter, nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone from 235 regulatory monitoring stations. Using a time-stratified case-crossover design, we performed conditional logistic regression to estimate odds ratios (OR) of KD according to interquartile range increases in each air pollutant concentration on the day of fever onset after adjusting for temperature and relative humidity. We identified 51 486 children treated for KD during the study period. An interquartile range increase (14.67 μg/m3) of particulate matter ≤2.5 µm was positively associated with KD at lag 1 (OR, 1.016; 95% CI, 1.004-1.029). An interquartile range increase (2.79 ppb) of sulfur dioxide concentration was associated with KD at all lag days (OR, 1.018; 95% CI, 1.002-1.034 at lag 0; OR, 1.022; 95% CI, 1.005-1.038 at lag 1; OR, 1.017; 95% CI, 1.001-1.033 at lag 2). Results were qualitatively similar in the second scenario of different fever onset, 2-pollutant model and sensitivity analyses.
Conclusions:
In a KD-focused national cohort of children, exposure to particulate matter ≤2.5 µm and sulfur dioxide was positively associated with the risk of KD. This finding supports the triggering role of ambient air pollution in the development of KD.




J Am Heart Assoc: 27 Apr 2022:e024092; epub ahead of print
Kwon D, Choe YJ, Kim SY, Chun BC, Choe SA
J Am Heart Assoc: 27 Apr 2022:e024092; epub ahead of print | PMID: 35475377
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Impact:
Abstract

Acetylsalicylic Acid Is Associated With a Lower Prevalence of Ascending Aortic Aneurysm and a Decreased Aortic Expression of Cyclooxygenase 2.

Granath C, Freiholtz D, Bredin F, Olsson C, Franco-Cereceda A, Björck HM

Background:
Acetylsalicylic acid (ASA) therapy has been associated with a reduced prevalence and growth rate of abdominal as well as intracranial aneurysms, but the relationship between ASA and ascending aortic aneurysm formation remains largely unknown. The aim of the present study was to investigate whether ASA therapy is associated with a lower prevalence of ascending aortic aneurysm in a surgical cohort. Methods and Results One thousand seven hundred patients undergoing open-heart surgery for ascending aortic aneurysm and/or aortic valve disease were studied in this retrospective cross-sectional study. Aortic dilatation was defined as an aortic root or ascending aortic diameter ≥45 mm. Medications were self-reported by the patients in a systematic questionnaire. Cyclooxygenase gene expression was measured in the intima-media portion of the ascending aorta (n=117). In a multivariable analysis, ASA was associated with a reduced prevalence of ascending aortic aneurysm (relative risk, 0.68 [95% CI, 0.48-0.95], P=0.026) in patients with tricuspid aortic valves, but not in patients with bicuspid aortic valves (relative risk, 0.93 [95% CI, 0.64-1.34], P=0.687). Intima-media cyclooxygenase expression was positively correlated with ascending aortic dimensions (P<0.001 for cyclooxygenase-1 and P=0.05 for cyclooxygenase-2). In dilated, but not nondilated tricuspid aortic valve aortic specimens, ASA was associated with significantly lower cyclooxygenase-2 levels (P=0.034).
Conclusions:
Our findings are consistent with the hypothesis that ASA treatment may attenuate ascending aortic aneurysmal growth, possibly via cyclooxygenase-2 inhibition in the ascending aortic wall and subsequent anti-inflammatory actions.




J Am Heart Assoc: 26 Apr 2022:e024346; epub ahead of print
Granath C, Freiholtz D, Bredin F, Olsson C, Franco-Cereceda A, Björck HM
J Am Heart Assoc: 26 Apr 2022:e024346; epub ahead of print | PMID: 35470674
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Impact:
Abstract

Cardiovascular Risk and Treatment Outcomes in Severe Hypercholesterolemia: A Nationwide Cohort Study.

Lee CJ, Park S, Han K, Lee SH

Background:
This study aimed to evaluate the cardiovascular risk and outcomes after lipid reduction in patients with severe hypercholesterolemia using a nationwide cohort. Methods and Results This study used the database from the National Health Insurance Service of Korea. Among individuals who underwent regular health examination and follow-up, 2 377 918 were enrolled and categorized into 3 groups with severe hypercholesterolemia according to low-density lipoprotein cholesterol (LDL-C) levels, namely, ≥260, 225 to 259, and 190 to 224 mg/dL groups, and a control group (<160 mg/dL). Risks of composite cardiovascular events (myocardial infarction, coronary revascularization, and ischemic stroke) and total mortality were compared. In statin new users, the outcomes after statin use were further analyzed according to posttreatment LDL-C levels. The prevalence of individuals with LDL-C≥190 mg/dL was 1 of 106. Adjusted hazard ratios of composite events and total mortality (median follow-up, 6.1 years) in the groups ranged up to 2.4 (log-rank P<0.0001) and 2.3 (log-rank P=0.0002), respectively, and were dependent on LDL-C levels. The risks of each event were up to 4.1-, 3.8-, and 1.9-fold higher, respectively, in these groups. The risk of composite events (median follow-up, 6.2 years) was lower after lipid lowering; particularly, the risk was lowest in the group showing LDL-C<100 mg/dL after treatment (hazard ratio, 0.56, log-rank P=0.043).
Conclusions:
Using large Korean cohort data, our study proved incrementally elevated cardiovascular risk and clinical benefit associated with LDL-C<100 mg/dL in individuals with severe hypercholesterolemia. These results support aggressive lipid lowering and provide evidence for the LDL-C target in this population.




J Am Heart Assoc: 26 Apr 2022:e024379; epub ahead of print
Lee CJ, Park S, Han K, Lee SH
J Am Heart Assoc: 26 Apr 2022:e024379; epub ahead of print | PMID: 35470675
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Impact:
Abstract

Weak Association Between Genetic Markers of Hyperuricemia and Cardiorenal Outcomes: Insights From the STANISLAS Study Cohort With a 20-Year Follow-Up.

Kanbay M, Xhaard C, Le Floch E, Dandine-Roulland C, ... Zannad F, Rossignol P

Background:
Hyperuricemia is associated with poor cardiovascular outcomes, although it is uncertain whether this relationship is causal in nature. This study aimed to: (1) assess the heritability of serum uric acid (SUA) levels, (2) conduct a genome-wide association study on SUA levels, and (3) investigate the association between certain single-nucleotide polymorphisms and target organ damage. Methods and Results The STANISLAS (Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux) study cohort is a single-center longitudinal cohort recruited between 1993 and 1995 (visit 1), with a last visit (visit 4 [V4]) performed ≈20 years apart. Serum lipid profile, SUA, urinary albumin/creatinine ratio, estimated glomerular filtration rate, 24-hour ambulatory blood pressure monitoring, transthoracic echocardiography, pulse wave velocity, and genotyping for each participant were assessed at V4. A total of 1573 participants were included at V4, among whom 1417 had available SUA data at visit 1. Genome-wide association study results highlighted multiple single-nucleotide polymorphisms on the SLC2A9 gene linked to SUA levels. Carriers of the most associated mutated SLC2A9 allele (rs16890979) had significantly lower SUA levels. Although SUA level at V4 was highly associated with diabetes, prediabetes, higher body mass index, CRP (C-reactive protein) levels, estimated glomerular filtration rate variation (visit 1-V4), carotid intima-media thickness, and pulse wave velocity, rs16890979 was only associated with higher carotid intima-media thickness.
Conclusions:
Our findings demonstrate that rs16890979, a genetic determinant of SUA levels located on the SLC2A9 gene, is associated with carotid intima-media thickness despite significant associations between SUA levels and several clinical outcomes, thereby lending support to the hypothesis of a link between SUA and cardiovascular disease.




J Am Heart Assoc: 26 Apr 2022:e023301; epub ahead of print
Kanbay M, Xhaard C, Le Floch E, Dandine-Roulland C, ... Zannad F, Rossignol P
J Am Heart Assoc: 26 Apr 2022:e023301; epub ahead of print | PMID: 35470676
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Abstract

Effect of Sacubitril/Valsartan on the Right Ventricular Function and Pulmonary Hypertension in Patients With Heart Failure With Reduced Ejection Fraction: A Systematic Review and Meta-Analysis of Observational Studies.

Zhang J, Du L, Qin X, Guo X

Background:
Sacubitril/valsartan (S/V) demonstrated significant effects in improving left ventricular performance and remodeling in patients with heart failure with reduced ejection fraction. However, its effects on the right ventricle remain unclear. This systematic review and meta-analysis aimed to assess the impact of S/V on right ventricular function and pulmonary hypertension. Methods and Results We searched PubMed, Embase, Cochrane Library, and Web of Science from January 2010 to April 2021 for studies reporting right ventricular and pulmonary pressure indexes following S/V treatment. The quality of included studies was assessed using the Newcastle-Ottawa scale. Variables were pooled using a random-effects model to estimate weighted mean differences with 95% CIs. We identified 10 eligible studies comprising 875 patients with heart failure with reduced ejection fraction (mean age, 62.2 years; 74.0% men), all of which were observational. Significant improvements on right ventricular function and pulmonary hypertension after S/V initiation were observed, including tricuspid annular plane systolic excursion (weighted mean difference, 1.26 mm; 95% CI, 0.33-2.18 mm; P=0.008), tricuspid annular peak systolic velocity (weighted mean difference, 0.85 cm/s; 95% CI, 0.25-1.45 cm/s; P=0.005), and systolic pulmonary arterial pressure (weighted mean difference, 7.21 mm Hg; 95% CI, 5.38-9.03 mm Hg; P<0.001). Besides, S/V had a significant beneficial impact on left heart function, which was consistent with previous studies. The quadratic regression model revealed a certain correlation between tricuspid annular plane systolic excursion and left ventricular ejection fraction after excluding the inappropriate data (P=0.026).
Conclusions:
This meta-analysis verified that S/V could improve right ventricular performance and pulmonary hypertension in heart failure with reduced ejection fraction, which did not seem to be fully dependent on the reverse remodeling of left ventricle. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42021247970.




J Am Heart Assoc: 26 Apr 2022:e024449; epub ahead of print
Zhang J, Du L, Qin X, Guo X
J Am Heart Assoc: 26 Apr 2022:e024449; epub ahead of print | PMID: 35470677
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Impact:
Abstract

Assessment of Visit-to-Visit Blood Pressure Variability in Adults With Optimal Blood Pressure: A New Player in the Evaluation of Residual Cardiovascular Risk?

Liu M, Chen X, Zhang S, Lin J, ... Liao X, Zhuang X

Background:
There is a paucity of evidence regarding the association between visit-to-visit blood pressure variability and residual cardiovascular risk. We aimed to provide relevant evidence by determining whether high systolic blood pressure (SBP) variability in the optimal SBP levels still influences the risk of cardiovascular disease. Methods and Results We studied 7065 participants (aged 59.3±5.6 years; 44.3% men; and 82.9% White) in the ARIC (Atherosclerosis Risk in Communities) study with optimal SBP levels from visit 1 to visit 3. Visit-to-visit SBP variability was measured by variability independent of the mean in the primary analysis. The primary outcome was the major adverse cardiovascular event (MACE), defined as the first occurrence of all-cause mortality, coronary heart disease, stroke, and heart failure. During a median follow-up of 19.6 years, 2691 participants developed MACEs. After multivariable adjustment, the MACE risk was higher by 21% in participants with the highest SBP variability (variability independent of the mean quartile 4) compared with the lowest SBP variability participants (variability independent of the mean quartile 1) (hazard ratio, 1.21; 95% CI, 1.09-1.35). The restricted cubic spline showed that the hazard ratio for MACE was relatively linear, with a higher variability independent of the mean being associated with higher risk. These association were also found in the stratified analyses of participants with or without hypertension.
Conclusions:
In adults with optimal SBP levels, higher visit-to-visit SBP variability was significantly associated with a higher risk of MACE regardless of whether they had hypertension. Therefore, it may be necessary to further focus on the visit-to-visit SBP variability even at the guideline-recommended optimal blood pressure levels.




J Am Heart Assoc: 26 Apr 2022:e022716; epub ahead of print
Liu M, Chen X, Zhang S, Lin J, ... Liao X, Zhuang X
J Am Heart Assoc: 26 Apr 2022:e022716; epub ahead of print | PMID: 35470678
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Impact:
Abstract

Ongoing Exercise Intolerance Following COVID-19: A Magnetic Resonance-Augmented Cardiopulmonary Exercise Test Study.

Brown JT, Saigal A, Karia N, Patel RK, ... Muthurangu V, Knight DS

Background:
Ongoing exercise intolerance of unclear cause following COVID-19 infection is well recognized but poorly understood. We investigated exercise capacity in patients previously hospitalized with COVID-19 with and without self-reported exercise intolerance using magnetic resonance-augmented cardiopulmonary exercise testing. Methods and Results Sixty subjects were enrolled in this single-center prospective observational case-control study, split into 3 equally sized groups: 2 groups of age-, sex-, and comorbidity-matched previously hospitalized patients following COVID-19 without clearly identifiable postviral complications and with either self-reported reduced (COVIDreduced) or fully recovered (COVIDnormal) exercise capacity; a group of age- and sex-matched healthy controls. The COVIDreducedgroup had the lowest peak workload (79W [Interquartile range (IQR), 65-100] versus controls 104W [IQR, 86-148]; P=0.01) and shortest exercise duration (13.3±2.8 minutes versus controls 16.6±3.5 minutes; P=0.008), with no differences in these parameters between COVIDnormal patients and controls. The COVIDreduced group had: (1) the lowest peak indexed oxygen uptake (14.9 mL/minper kg [IQR, 13.1-16.2]) versus controls (22.3 mL/min per kg [IQR, 16.9-27.6]; P=0.003) and COVIDnormal patients (19.1 mL/min per kg [IQR, 15.4-23.7]; P=0.04); (2) the lowest peak indexed cardiac output (4.7±1.2 L/min per m2) versus controls (6.0±1.2 L/min per m2; P=0.004) and COVIDnormal patients (5.7±1.5 L/min per m2; P=0.02), associated with lower indexed stroke volume (SVi:COVIDreduced 39±10 mL/min per m2 versus COVIDnormal 43±7 mL/min per m2 versus controls 48±10 mL/min per m2; P=0.02). There were no differences in peak tissue oxygen extraction or biventricular ejection fractions between groups. There were no associations between COVID-19 illness severity and peak magnetic resonance-augmented cardiopulmonary exercise testing metrics. Peak indexed oxygen uptake, indexed cardiac output, and indexed stroke volume all correlated with duration from discharge to magnetic resonance-augmented cardiopulmonary exercise testing (P<0.05).
Conclusions:
Magnetic resonance-augmented cardiopulmonary exercise testing suggests failure to augment stroke volume as a potential mechanism of exercise intolerance in previously hospitalized patients with COVID-19. This is unrelated to disease severity and, reassuringly, improves with time from acute illness.




J Am Heart Assoc: 26 Apr 2022:e024207; epub ahead of print
Brown JT, Saigal A, Karia N, Patel RK, ... Muthurangu V, Knight DS
J Am Heart Assoc: 26 Apr 2022:e024207; epub ahead of print | PMID: 35470679
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Abstract

Establishment of a Dedicated Inherited Cardiomyopathy Clinic: From Challenges to Improved Patients\' Outcome.

Smith E, Thompson PD, Burke-Martindale C, Weissler-Snir A

Background:
Inherited cardiomyopathies (ICs) are relatively rare. General cardiologists have little experience in diagnosing and managing these conditions. International societies have recognized the need for dedicated IC clinics. However, only few reports on such clinics are available. Methods and Results Clinical data of patients referred to our clinic during its first 2 years for a personal or family history of (possible) IC were analyzed. A total of 207 patients from 196 families were seen; 13% of probands had their diagnosis changed. Diagnosis was most commonly altered in patients referred for possible arrhythmogenic dominant right ventricular cardiomyopathy (62.5%). A total of 90% of probands had genetic testing, of whom 27.3% harbored a likely pathogenic or pathogenic variant. Of patients with confirmed hypertrophic cardiomyopathy, 31 (28.7%) were treated for left ventricular outflow tract obstruction, including septal reduction in 13. Patients with either hypertrophic cardiomyopathy or left ventricular noncompaction and a history of atrial fibrillation were started on oral anticoagulation. Oral anticoagulation was also discussed with all patients with hypertrophic cardiomyopathy and apical aneurysm. Patients with a definite diagnosis of arrhythmogenic dominant right ventricular cardiomyopathy were started on β-blockers and given restrictive exercise prescriptions. A total of 17 patients with hypertrophic cardiomyopathy and 5 patients with likely pathogenic or likely variants in arrhythmogenic genes received primary prevention implantable cardioverter-defibrillators. No implantable cardioverter-defibrillators were warranted for arrhythmogenic dominant right ventricular cardiomyopathy. A total of 76 family members from 24 families had cascade screening, 32 of whom carried the familial variant. A total of 21 members from 13 gene-elusive families were evaluated by clinical screening, 3 of whom had positive screening.
Conclusions:
Specialized IC clinics may improve diagnosis, management, and outcomes of patients with (possible) IC and their family members.




J Am Heart Assoc: 26 Apr 2022:e024501; epub ahead of print
Smith E, Thompson PD, Burke-Martindale C, Weissler-Snir A
J Am Heart Assoc: 26 Apr 2022:e024501; epub ahead of print | PMID: 35470680
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Abstract

Stent Optimization Using Optical Coherence Tomography and Its Prognostic Implications After Percutaneous Coronary Intervention.

Rai H, Harzer F, Otsuka T, Abdelwahed YS, ... Kastrati A, Joner M

Background:
Stent underexpansion has been known to be associated with worse outcomes. We sought to define optical coherence tomography assessed optimal stent expansion index (SEI), which associates with lower incidence of follow-up major adverse cardiac events (MACEs). Methods and Results A total of 315 patients (involving 370 lesions) who underwent optical coherence tomography-aided coronary stenting were retrospectively included. SEI was calculated separately for equal halves of each stented segment using minimum stent area/mean reference lumen area ([proximal reference area+distal reference area]/2). The smaller of the 2 was considered to be the SEI of that case. Follow-up MACE was defined as a composite of all-cause death, myocardial infarction, stent thrombosis, and target lesion revascularization. Average minimum stent area was 6.02 (interquartile range, 4.65-7.92) mm2, while SEI was 0.79 (interquartile range, 0.71-0.86). Forty-seven (12.7%) incidences of MACE were recorded for 370 included lesions during a median follow-up duration of 557 (interquartile range, 323-1103) days. Receiver operating characteristic curve analysis identified 0.85 as the best SEI cutoff (<0.85) to predict follow-up MACE (area under the curve, 0.60; sensitivity, 0.85; specificity, 0.34). MACE was observed in 40 of 260 (15.4%) lesions with SEI <0.85 and in 7 of 110 (6.4%) lesions with SEI ≥0.85 (P=0.02). Least absolute shrinkage and selection operator regression identified SEI <0.85 (odds ratio, 3.55; 95% CI, 1.40-9.05; P<0.01) and coronary calcification (odds ratio, 2.47; 95% CI, 1.00-6.10; P=0.05) as independent predictors of follow-up MACE.
Conclusions:
The present study identified SEI <0.85, associated with increased incidence of MACE, as the optimal cutoff in daily practice. Along with suboptimal SEI (<0.85), coronary calcification was also found to be a significant predictor of follow-up MACE.




J Am Heart Assoc: 26 Apr 2022:e023493; epub ahead of print
Rai H, Harzer F, Otsuka T, Abdelwahed YS, ... Kastrati A, Joner M
J Am Heart Assoc: 26 Apr 2022:e023493; epub ahead of print | PMID: 35470682
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Abstract

Epidemiology and Management of ST-Segment-Elevation Myocardial Infarction in Patients With COVID-19: A Report From the American Heart Association COVID-19 Cardiovascular Disease Registry.

Bhatt AS, Varshney AS, Goodrich EL, Gong J, ... Morrow DA, Bohula EA

Background:
Early reports from the COVID-19 pandemic identified coronary thrombosis leading to ST-segment-elevation myocardial infarction (STEMI) as a complication of COVID-19 infection. However, the epidemiology of STEMI in patients with COVID-19 is not well characterized. We sought to determine the incidence, diagnostic and therapeutic approaches, and outcomes in STEMI patients hospitalized for COVID-19. Methods and Results Patients with data on presentation ECG and in-hospital myocardial infarction were identified from January 14, 2020 to November 30, 2020, from 105 sites participating in the American Heart Association COVID-19 Cardiovascular Disease Registry. Patient characteristics, resource use, and clinical outcomes were summarized and compared based on the presence or absence of STEMI. Among 15 621 COVID-19 hospitalizations, 54 (0.35%) patients experienced in-hospital STEMI. Among patients with STEMI, the majority (n=40, 74%) underwent transthoracic echocardiography, but only half (n=27, 50%) underwent coronary angiography. Half of all patients with COVID-19 and STEMI (n=27, 50%) did not undergo any form of primary reperfusion therapy. Rates of all-cause shock (47% versus 14%), cardiac arrest (22% versus 4.8%), new heart failure (17% versus 1.4%), and need for new renal replacement therapy (11% versus 4.3%) were multifold higher in patients with STEMI compared with those without STEMI (P<0.050 for all). Rates of in-hospital death were 41% in patients with STEMI, compared with 16% in those without STEMI (P<0.001).
Conclusions:
STEMI in hospitalized patients with COVID-19 is rare but associated with poor in-hospital outcomes. Rates of coronary angiography and primary reperfusion were low in this population of patients with STEMI and COVID-19. Adaptations of systems of care to ensure timely contemporary treatment for this population are needed.




J Am Heart Assoc: 26 Apr 2022:e024451; epub ahead of print
Bhatt AS, Varshney AS, Goodrich EL, Gong J, ... Morrow DA, Bohula EA
J Am Heart Assoc: 26 Apr 2022:e024451; epub ahead of print | PMID: 35470683
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Abstract

Diagnostic Yield of Genetic Testing in Young Patients With Atrioventricular Block of Unknown Cause.

Resdal Dyssekilde J, Frederiksen TC, Christiansen MK, Hasle Sørensen R, ... Nygaard M, Jensen HK

Background:
The cause of atrioventricular block (AVB) remains unknown in approximately half of young patients with the diagnosis. Although variants in several genes associated with cardiac conduction diseases have been identified, the contribution of genetic variants in younger patients with AVB is unknown. Methods and Results Using the Danish Pacemaker and Implantable Cardioverter Defibrillator (ICD) Registry, we identified all patients younger than 50 years receiving a pacemaker because of AVB in Denmark in the period from January 1, 1996 to December 31, 2015. From medical records, we identified patients with unknown cause of AVB at time of pacemaker implantation. These patients were invited to a genetic screening using a panel of 102 genes associated with inherited cardiac diseases. We identified 471 living patients with AVB of unknown cause, of whom 226 (48%) accepted participation. Median age at the time of pacemaker implantation was 39 years (interquartile range, 32-45 years), and 123 (54%) were men. We found pathogenic or likely pathogenic variants in genes associated with or possibly associated with AVB in 12 patients (5%). Most variants were found in the LMNA gene (n=5). LMNA variant carriers all had a family history of either AVB and/or sudden cardiac death.
Conclusions:
In young patients with AVB of unknown cause, we found a possible genetic cause in 1 out of 20 participating patients. Variants in the LMNA gene were most common and associated with a family history of AVB and/or sudden cardiac death, suggesting that genetic testing should be a part of the diagnostic workup in these patients to stratify risk and screen family members.




J Am Heart Assoc: 26 Apr 2022:e025643; epub ahead of print
Resdal Dyssekilde J, Frederiksen TC, Christiansen MK, Hasle Sørensen R, ... Nygaard M, Jensen HK
J Am Heart Assoc: 26 Apr 2022:e025643; epub ahead of print | PMID: 35470684
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Abstract

Platelet Function Is Associated With Dementia Risk in the Framingham Heart Study.

Ramos-Cejudo J, Johnson AD, Beiser A, Seshadri S, ... Wisniewski TM, Osorio RS

Background:
Vascular function is compromised in Alzheimer disease (AD) years before amyloid and tau pathology are detected and a substantial body of work shows abnormal platelet activation states in patients with AD. The aim of our study was to investigate whether platelet function in middle age is independently associated with future risk of AD. Methods and Results We examined associations of baseline platelet function with incident dementia risk in the community-based FHS (Framingham Heart Study) longitudinal cohorts. The association between platelet function and risk of dementia was evaluated using the cumulative incidence function and inverse probability weighted Cox proportional cause-specific hazards regression models, with adjustment for demographic and clinical covariates. Platelet aggregation response was measured by light transmission aggregometry. The final study sample included 1847 FHS participants (average age, 53.0 years; 57.5% women). During follow-up (median, 20.5 years), we observed 154 cases of incident dementia, of which 121 were AD cases. Results from weighted models indicated that platelet aggregation response to adenosine diphosphate 1.0 µmol/L was independently and positively associated with dementia risk, and it was preceded in importance only by age and hypertension. Sensitivity analyses showed associations with the same directionality for participants defined as adenosine diphosphate hyper-responders, as well as the platelet response to 0.1 µmol/L epinephrine.
Conclusions:
Our study shows individuals free of antiplatelet therapy with a higher platelet response are at higher risk of dementia in late life during a 20-year follow-up, reinforcing the role of platelet function in AD risk. This suggests that platelet phenotypes may be associated with the rate of dementia and potentially have prognostic value.




J Am Heart Assoc: 26 Apr 2022:e023918; epub ahead of print
Ramos-Cejudo J, Johnson AD, Beiser A, Seshadri S, ... Wisniewski TM, Osorio RS
J Am Heart Assoc: 26 Apr 2022:e023918; epub ahead of print | PMID: 35470685
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Abstract

Coronary Flow Variations Following Percutaneous Coronary Intervention Affect Diastolic Nonhyperemic Pressure Ratios More Than the Whole Cycle Ratios.

Aetesam-Ur-Rahman M, Zhao TX, Paques K, Oliveira J, ... West NEJ, Hoole SP

Background:
Post-percutaneous coronary intervention (PCI) fractional flow reserve ≥0.90 is an accepted marker of procedural success, and a cutoff of ≥0.95 has recently been proposed for post-PCI instantaneous wave-free ratio. However, stability of nonhyperemic pressure ratios (NHPRs) post-PCI is not well characterized, and transient reactive submaximal hyperemia post-PCI may affect their precision. We performed this study to assess stability and reproducibility of NHPRs post-PCI. Methods and Results Fifty-seven patients (age, 63.77±10.67 years; men, 71%) underwent hemodynamic assessment immediately post-PCI and then after a recovery period of 10, 20, and 30 minutes and repeated at 3 months. Manual offline analysis was performed to derive resting and hyperemic pressure indexes (Pd/Pa resting pressure gradient, mathematically derived instantaneous wave-free ratio, resting full cycle ratio, and fractional flow reserve) and microcirculatory resistances (basal microvascular resistance and index of microvascular resistance). Transient submaximal hyperemia occurring post-PCI was demonstrated by longer thermodilution time at 30 minutes compared with immediately post-PCI; mean difference of thermodilution time was 0.17 seconds (95% CI, 0.07-0.26 seconds; P=0.04). Basal microcirculatory resistance was also higher at 30 minutes than immediately post-PCI; mean difference of basal microvascular resistance was 10.89 mm Hg.s (95% CI, 2.25-19.52 mm Hg.s; P=0.04). Despite this, group analysis confirmed no significant differences in the values of resting whole cycle pressure ratios (Pd/Pa and resting full cycle ratio) as well as diastolic pressure ratios (diastolic pressure ratio and mathematically derived instantaneous wave-free ratio). Whole cardiac cycle NHPRs demonstrated the best overall stability post-PCI, and 1 in 5 repeated diastolic NHPRs crossed the clinical decision threshold.
Conclusions:
Whole cycle NHPRs demonstrate better reproducibility and clinical precision post-PCI than diastolic NHPRs, possibly because of less perturbation from predominantly diastolic reactive hyperemia and left ventricular stunning. Registration URL: https://clinicaltrials.gov/ct2/show/NCT03502083; Unique identifier: NCT03502083 and URL: https://clinicaltrials.gov/ct2/show/NCT03076476; Unique identifier: NCT03076476.




J Am Heart Assoc: 26 Apr 2022:e023554; epub ahead of print
Aetesam-Ur-Rahman M, Zhao TX, Paques K, Oliveira J, ... West NEJ, Hoole SP
J Am Heart Assoc: 26 Apr 2022:e023554; epub ahead of print | PMID: 35470686
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Abstract

Sex-Related Differences in Genetic Cardiomyopathies.

Argirò A, Ho C, Day SM, van der Velden J, ... Lakdawala NK, Olivotto I
Cardiomyopathies are a heterogeneous collection of diseases that have in common primary functional and structural abnormalities of the heart muscle, often genetically determined. The most effective categorization of cardiomyopathies is based on the presenting phenotype, with hypertrophic, dilated, arrhythmogenic, and restrictive cardiomyopathy as the prototypes. Sex modulates the prevalence, morpho-functional manifestations and clinical course of cardiomyopathies. Aspects as diverse as ion channel expression and left ventricular remodeling differ in male and female patients with myocardial disease, although the reasons for this are poorly understood. Moreover, clinical differences may also result from complex societal/environmental discrepancies between sexes that may disadvantage women. This review provides a state-of-the-art appraisal of the influence of sex on cardiomyopathies, highlighting the many gaps in knowledge and open research questions.



J Am Heart Assoc: 26 Apr 2022:e024947; epub ahead of print
Argirò A, Ho C, Day SM, van der Velden J, ... Lakdawala NK, Olivotto I
J Am Heart Assoc: 26 Apr 2022:e024947; epub ahead of print | PMID: 35470690
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Abstract

Anxiety and Depression Following Aortic Valve Replacement.

Wegermann ZK, Mack MJ, Arnold SV, Thompson CA, ... Alexander KP, Brennan JM

Background:
The aim of this study was to identify patients vulnerable for anxiety and/or depression following aortic valve replacement (AVR) and to evaluate factors that may mitigate this risk. Methods and Results This is a retrospective cohort study conducted using a claims database; 18 990 patients (1/2013-12/2018) ≥55 years of age with 6 months of pre-AVR data were identified. Anxiety and/or depression risk was compared at 3 months, 6 months, and 1 year following transcatheter aortic valve replacement or surgical AVR (SAVR) after risk adjustment using logistic regression and Cox proportional hazards models. Separate models were estimated for patients with and without surgical complications and discharge location. Patients with SAVR experienced a higher relative risk of anxiety and/or depression at 3 months (12.4% versus 8.8%; adjusted hazard ratio [HR] 1.39 [95% CI, 1.19-1.63]) and 6 months (15.6% versus 13.0%; adjusted HR, 1.24 [95% CI, 1.08-1.42]), with this difference narrowing by 12 months (20.1% versus 19.3%; adjusted HR, 1.14 [95% CI, 1.01-1.29]) after AVR. This association was most pronounced among patients discharged to home, with patients with SAVR having a higher relative risk of anxiety and/or depression. In patients who experienced operative complications, there was no difference between SAVR and transcatheter aortic valve replacement. However, among patients without operative complications, patients with SAVR had an increased risk of postoperative anxiety and/or depression at 3 months (adjusted HR, 1.47 [95% CI, 1.23-1.75]) and 6 months (adjusted HR 1.26 [95% CI, 1.08-1.46]), but not at 12 months.
Conclusions:
There is an associated reduction in the risk of new-onset anxiety and/or depression among patients undergoing transcatheter aortic valve replacement (versus SAVR), particularly in the first 3 and 6 months following treatment.




J Am Heart Assoc: 26 Apr 2022:e024377; epub ahead of print
Wegermann ZK, Mack MJ, Arnold SV, Thompson CA, ... Alexander KP, Brennan JM
J Am Heart Assoc: 26 Apr 2022:e024377; epub ahead of print | PMID: 35470691
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Impact:
Abstract

Microcirculatory Function in Nonhypertrophic and Hypertrophic Myocardium in Patients With Aortic Valve Stenosis.

Sabbah M, Olsen NT, Minkkinen M, Holmvang L, ... Lønborg J, Engstrøm T

Background:
Left ventricular hypertrophy (LVH) has often been supposed to be associated with abnormal myocardial blood flow and resistance. The aim of this study was to evaluate and quantify the physiological and pathological changes in myocardial blood flow and microcirculatory resistance in patients with and without LVH attributable to severe aortic stenosis. Methods and Results Absolute coronary blood flow and microvascular resistance were measured using a novel technique with continuous thermodilution and infusion of saline. In addition, myocardial mass was assessed with cardiac magnetic resonance imaging. Fifty-three patients with aortic valve stenosis were enrolled in the study. In 32 patients with LVH, hyperemic blood flow per gram of tissue was significantly decreased compared with 21 patients without LVH (1.26±0.48 versus 1.66±0.65 mL·min-1·g-1; P=0.018), whereas minimal resistance indexed for left ventricular mass was significantly increased in patients with LVH (63 [47-82] versus 43 [35-63] Wood Units·kg; P=0.014).
Conclusions:
Patients with LVH attributable to severe aortic stenosis had lower hyperemic blood flow per gram of myocardium and higher minimal myocardial resistance compared with patients without LVH.




J Am Heart Assoc: 26 Apr 2022:e025381; epub ahead of print
Sabbah M, Olsen NT, Minkkinen M, Holmvang L, ... Lønborg J, Engstrøm T
J Am Heart Assoc: 26 Apr 2022:e025381; epub ahead of print | PMID: 35470693
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Impact:
Abstract

Incremental Prognosis by Left Atrial Functional Assessment: The Left Atrial Coupling Index in Patients With Floppy Mitral Valves.

Essayagh B, Benfari G, Antoine C, Maalouf J, ... Michelena HI, Enriquez-Sarano M

Background:
Emerging data suggest important prognostic value to left atrial (LA) characteristics, but the independent impact of LA function on outcome remains unsubstantiated. Thus, we aimed to define the incremental prognostic value of LA coupling index (LACI), coupling volumetric and mechanical LA characteristics and calculated as the ratio of left atrial volume index to tissue Doppler imaging a\', in a large cohort of patients with isolated floppy mitral valve. Methods and Results All consecutive 4792 patients (61±16 years, 48% women) with isolated floppy mitral valve in sinus rhythm diagnosed at Mayo Clinic from 2003 to 2011, comprehensively characterized and with prospectively measured left atrial volume index and tissue Doppler imaging a\' in routine practice, were enrolled, and their long-term survival analyzed. Overall, LACI was 5.8±3.7 and was <5 in 2422 versus ≥5 in 2370 patients. LACI was independently higher with older age, more mitral regurgitation (no 3.8±2.3, mild 5.1±3.0, moderate 6.5±3.8, and severe 7.8±4.3), and with diastolic (higher E/e\') and systolic (higher end-systolic dimension) left ventricular dysfunction (all P≤0.0001). At diagnosis, higher LACI was associated with more severe presentation (more dyspnea, more severe functional tricuspid regurgitation, and elevated pulmonary artery pressure, all P≤0.0001) independently of age, sex, comorbidity index, ventricular function, and mitral regurgitation severity. During 7.0±3.0 years follow-up, 1146 patients underwent mitral valve surgery (94% repair, 6% replacement), and 880 died, 780 under medical management. In spline curve analysis, LACI ≥5 was identified as the threshold for excess mortality, with much reduced 10-year survival under medical management (60±2% versus 85±1% for LACI <5, P<0.0001), even after comprehensive adjustment (adjusted hazard ratio, 1.30 [95% CI, 1.10-1.53] for LACI ≥5; P=0.002). Association of LACI ≥5 with higher mortality persisted, stratifying by mitral regurgitation severity of LA enlargement grade (all P<0.001) and after propensity-score matching (P=0.02). Multiple statistical methods confirmed the significant incremental predictive power of LACI over left atrial volume index (all P<0.0001).
Conclusions:
LA functional assessment by LACI in routine practice is achievable in a large number of patients with floppy mitral valve using conventional Doppler echocardiographic measurements. Higher LACI is associated with worse clinical presentation, but irrespective of baseline characteristics, LACI is strongly, independently, and incrementally determinant of outcome, demonstrating the crucial importance of LA functional response to mitral valve disease.




J Am Heart Assoc: 26 Apr 2022:e024814; epub ahead of print
Essayagh B, Benfari G, Antoine C, Maalouf J, ... Michelena HI, Enriquez-Sarano M
J Am Heart Assoc: 26 Apr 2022:e024814; epub ahead of print | PMID: 35470696
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Impact:
Abstract

Plasma Total Homocysteine Level Is Related to Unfavorable Outcomes in Ischemic Stroke With Atrial Fibrillation.

Nam KW, Kim CK, Yu S, Oh K, ... Hwang YH, Seo WK

Background:
Unlike patients with stroke caused by other mechanisms, the effect of elevated plasma total homocysteine (tHcy) on the prognosis of patients with both ischemic stroke and atrial fibrillation (AF) is unknown. This study aimed to evaluate the association between tHcy level and the functional outcome of patients with AF-related stroke. Methods and Results We included consecutive patients with AF-related stroke between 2013 and 2015 from the registry of a real-world prospective cohort from 11 large centers in South Korea. A 3-month modified Rankin Scale score ≥3 was considered an unfavorable outcome. Since tHcy is strongly affected by renal function, we performed a subgroup analysis according to the presence of renal dysfunction. A total of 910 patients with AF-related stroke were evaluated (mean age, 73 years; male sex, 56.0%). The mean tHcy level was 11.98±8.81 μmol/L. In multivariable analysis, the tHcy level (adjusted odds ratio, 1.04; 95% CI, 1.01-1.07, per 1 μmol/L) remained significantly associated with unfavorable outcomes. In the subgroup analysis based on renal function, tHcy values above the cutoff point (≥14.60 μmol/L) showed a close association with the unfavorable outcome only in the normal renal function group (adjusted odds ratio, 3.10; 95% CI, 1.60-6.01). In patients with renal dysfunction, tHcy was not significantly associated with the prognosis of AF-related stroke.
Conclusions:
A higher plasma tHcy level was associated with unfavorable outcomes in patients with AF-related stroke. This positive association may vary according to renal function but needs to be verified in further studies.




J Am Heart Assoc: 26 Apr 2022:e022138; epub ahead of print
Nam KW, Kim CK, Yu S, Oh K, ... Hwang YH, Seo WK
J Am Heart Assoc: 26 Apr 2022:e022138; epub ahead of print | PMID: 35470699
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Impact:
Abstract

Psychological Distress in Adults With Congenital Heart Disease Over the COVID-19 Pandemic.

Janzen ML, LeComte K, Sathananthan G, Wang J, ... Chakrabarti S, Grewal J

Background:
This study sought to better understand the experiences of adults with congenital heart disease throughout the pandemic. Objectives were to determine (1) psychological distress before and throughout the pandemic; (2) changes in day-to-day functioning; and (3) the percentage of adults with congenital heart disease who experienced COVID-19 related symptoms, underwent testing, and tested positive. Methods and Results This was a cross-sectional study paired with retrospective chart review. A web-based survey was distributed to patients between December 2020 and January 2021. Patients reported on psychological distress across 5 categories (Screening Tool for Psychological Distress; depression, anxiety, stress, anger, and lack of social support), whether they experienced symptoms of COVID-19 and/or sought testing, and changes to their work and social behavior. Five hundred seventy-nine survey responses were received, of which 555 were linked to clinical data. Patients were aged 45±15 years. The proportion of patients reporting above-threshold values for all Screening Tool for Psychological Distress items significantly increased during the early pandemic compared with before the pandemic. Stress returned to baseline in December 2020/January 2021, whereas all others remained elevated. Psychological distress decreased with age, and women reported persistently elevated stress and anxiety compared with men during the pandemic. A consistent trend was not observed with regard to American College of Cardiology/American Heart Association anatomic and physiologic classification. Fifty (9%) patients lost employment because of a COVID-19-related reason. COVID-19 symptoms were reported by 145 (25%) patients, 182 (31%) sought testing, and 10 (2%) tested positive.
Conclusions:
A substantial proportion of adults with congenital heart disease reported clinically significant psychological distress during the pandemic.




J Am Heart Assoc: 26 Apr 2022:e023516; epub ahead of print
Janzen ML, LeComte K, Sathananthan G, Wang J, ... Chakrabarti S, Grewal J
J Am Heart Assoc: 26 Apr 2022:e023516; epub ahead of print | PMID: 35470701
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Impact:
Abstract

Association of Accelerometer-Measured Sedentary Accumulation Patterns With Incident Cardiovascular Disease, Cancer, and All-Cause Mortality.

Dempsey PC, Strain T, Winkler EAH, Westgate K, ... Brage S, Wijndaele K

Background:
Emerging evidence suggests accruing sedentary behavior (SB) in relatively more prolonged periods may convey additional cardiometabolic risks, but few studies have examined prospective outcomes. We examined the association of SB accumulation patterns with incident cardiovascular disease (CVD), cancer, and all-cause mortality (ACM). Methods and Results Data were from 7671 EPIC-Norfolk (European Prospective Investigation Into Cancer and Nutrition-Norfolk) cohort middle- to older-aged adults who wore accelerometers on the right hip for 4 to 7 days. Cox proportional hazards regression modeled associations between 2 measures of SB accumulation and incident CVD, cancer, and ACM. These were usual SB bout duration (the midpoint of each individual\'s SB accumulation curve, fitted using nonlinear regression) and alpha (hybrid measure of bout frequency and duration, with higher values indicating relatively shorter bouts and fewer long bouts). Models were adjusted for potential confounders, then further for 24-hour time-use compositions. During mean follow-up time of 6.4 years, 339 ACM, 1106 CVD, and 516 cancer events occurred. Elevated rates of incident cancer and ACM were seen with more prolonged SB accumulation (lower alpha, higher usual SB bout duration) but not CVD. For usual SB bout duration and alpha, respectively, the confounder-adjusted hazard ratios per SD of the exposure were 1.12 (95% CI, 1.02-1.23) and 0.88 (95% CI, 0.79-0.98) with incident cancer and 1.16 (95% CI, 1.07-1.26) and 0.80 (95% CI, 0.72-0.89) with ACM (all P<0.05). Further adjustment for 24-hour time use weakened associations with ACM for usual bout duration (hazard ratio, 1.06; 95% CI, 0.97-1.16; P=0.209) and partially for alpha (hazard ratio, 0.87; 95% CI, 0.77-0.99; P=0.029).
Conclusions:
Accruing SB in longer bout durations was associated with higher rates of incident cancer and ACM but not with incident CVD, with some evidence of direct SB accumulation effects independent of 24-hour time use. Findings provide some support for considering SB accumulation as an adjunct target of messaging to \"sit less and move more.\"




J Am Heart Assoc: 26 Apr 2022:e023845; epub ahead of print
Dempsey PC, Strain T, Winkler EAH, Westgate K, ... Brage S, Wijndaele K
J Am Heart Assoc: 26 Apr 2022:e023845; epub ahead of print | PMID: 35470706
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Impact:
Abstract

Heart Failure and Patient-Reported Outcomes in Adults With Congenital Heart Disease from 15 Countries.

Lu CW, Wang JK, Yang HL, Kovacs AH, ... APPROACH‐IS consortium, the International Society for Adult Congenital Heart Disease (ISACHD) *

Background:
Heart failure (HF) is the leading cause of mortality and associated with significant morbidity in adults with congenital heart disease. We sought to assess the association between HF and patient-report outcomes in adults with congenital heart disease. Methods and Results As part of the APPROACH-IS (Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease-International Study), we collected data on HF status and patient-reported outcomes in 3959 patients from 15 countries across 5 continents. Patient-report outcomes were: perceived health status (12-item Short Form Health Survey), quality of life (Linear Analogue Scale and Satisfaction with Life Scale), sense of coherence-13, psychological distress (Hospital Anxiety and Depression Scale), and illness perception (Brief Illness Perception Questionnaire). In this sample, 137 (3.5%) had HF at the time of investigation, 298 (7.5%) had a history of HF, and 3524 (89.0%) had no current or past episode of HF. Patients with current or past HF were older and had a higher prevalence of complex congenital heart disease, arrhythmias, implantable cardioverter-defibrillators, other clinical comorbidities, and mood disorders than those who never had HF. Patients with HF had worse physical functioning, mental functioning, quality of life, satisfaction with life, sense of coherence, depressive symptoms, and illness perception scores. Magnitudes of differences were large for physical functioning and illness perception and moderate for mental functioning, quality of life, and depressive symptoms.
Conclusions:
HF in adults with congenital heart disease is associated with poorer patient-reported outcomes, with large effect sizes for physical functioning and illness perception. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT02150603.




J Am Heart Assoc: 26 Apr 2022:e024993; epub ahead of print
Lu CW, Wang JK, Yang HL, Kovacs AH, ... APPROACH‐IS consortium, the International Society for Adult Congenital Heart Disease (ISACHD) *
J Am Heart Assoc: 26 Apr 2022:e024993; epub ahead of print | PMID: 35470715
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Impact:
Abstract

Engaging Families in Adult Cardiovascular Care: A Scientific Statement From the American Heart Association.

Goldfarb MJ, Bechtel C, Capers Q, de Velasco A, ... Gulati M, American Heart Association Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Cardiovascular Radiology and Intervention; Council on Hypertension; Council on the Kidney in Cardiovascular Disease; and Council on Lifestyle and Cardiometabolic Health
Family engagement empowers family members to become active partners in care delivery. Family members increasingly expect and wish to participate in care and be involved in the decision-making process. The goal of engaging families in care is to improve the care experience to achieve better outcomes for both patients and family members. There is emerging evidence that engaging family members in care improves person- and family-important outcomes. Engaging families in adult cardiovascular care involves a paradigm shift in the current organization and delivery of both acute and chronic cardiac care. Many cardiovascular health care professionals have limited awareness of the role and potential benefits of family engagement in care. Additionally, many fail to identify opportunities to engage family members. There is currently little guidance on family engagement in any aspect of cardiovascular care. The objective of this statement is to inform health care professionals and stakeholders about the importance of family engagement in cardiovascular care. This scientific statement will describe the rationale for engaging families in adult cardiovascular care, outline opportunities and challenges, highlight knowledge gaps, and provide suggestions to cardiovascular clinicians on how to integrate family members into the health care team.



J Am Heart Assoc: 21 Apr 2022:e025859; epub ahead of print
Goldfarb MJ, Bechtel C, Capers Q, de Velasco A, ... Gulati M, American Heart Association Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Lifelong Congenital Heart Disease and Heart Health in the Young; Council on Cardiovascular Radiology and Intervention; Council on Hypertension; Council on the Kidney in Cardiovascular Disease; and Council on Lifestyle and Cardiometabolic Health
J Am Heart Assoc: 21 Apr 2022:e025859; epub ahead of print | PMID: 35446109
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Impact:
Abstract

Mediterranean-Style Diet and Risk of Preeclampsia by Race in the Boston Birth Cohort.

Minhas AS, Hong X, Wang G, Rhee DK, ... Wang X, Mueller NT

Background:
Preeclampsia is a major cause of maternal and fetal morbidity and mortality. Given its large public health burden, there is a need to identify modifiable factors that can be targeted for preeclampsia prevention. In this study, we examined whether a Mediterranean-style diet is protective for preeclampsia in a large cohort of racially and ethnically diverse, urban, low-income women. Methods and Results We used data from the Boston Birth Cohort. Maternal sociodemographic and dietary data were obtained via interview and food frequency questionnaire within 24 to 72 hours postpartum, respectively. Additional clinical information, including physician diagnoses of preexisting conditions and preeclampsia, were extracted from medical records. We derived a Mediterranean-style diet score from the food frequency questionnaire and performed logistic regression to examine the association of the Mediterranean-style diet score with preeclampsia. Of 8507 women in the sample, 848 developed preeclampsia. 47% were Black, 28% were Hispanic, and the remaining were White/Other. After multivariable adjustment, greatest adherence with MSD was associated with lower preeclampsia odds (adjusted odds ratio comparing tertile 3 to tertile 1, 0.78; 95% CI, 0.64-0.96). A subgroup analysis of Black women demonstrated a similar benefit with an adjusted odds ratio comparing tertile 3 to tertile 1 of 0.74 (95% CI, 0.76-0.96).
Conclusions:
Self-report of higher adherence to a Mediterranean-style diet is associated with lower preeclampsia odds, and benefit of this diet is present among Black women as well.




J Am Heart Assoc: 20 Apr 2022:e022589; epub ahead of print
Minhas AS, Hong X, Wang G, Rhee DK, ... Wang X, Mueller NT
J Am Heart Assoc: 20 Apr 2022:e022589; epub ahead of print | PMID: 35441523
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Impact:
Abstract

Need for Better and Broader Training in Cardio-Obstetrics: A National Survey of Cardiologists, Cardiovascular Team Members, and Cardiology Fellows in Training.

Bello NA, Agrawal A, Davis MB, Harrington CM, ... Walsh MN, Park K

Background:
Team-based models of cardio-obstetrics care have been developed to address the increasing rate of maternal mortality from cardiovascular diseases. Cardiovascular clinician and trainee knowledge and comfort with this topic, and the extent of implementation of an interdisciplinary approach to cardio-obstetrics, are unknown. Methods and Results We aimed to assess the current state of cardio-obstetrics knowledge, practices, and services provided by US cardiovascular clinicians and trainees. A survey developed in conjunction with the American College of Cardiology was circulated to a representative sample of cardiologists (N=311), cardiovascular team members (N=51), and fellows in training (N=139) from June 18, 2020, to July 29, 2020. Knowledge and attitudes about the provision of cardiovascular care to pregnant patients and the prevalence and composition of cardio-obstetrics teams were assessed. The widest knowledge gaps on the care of pregnant compared with nonpregnant patients were reported for medication safety (42%), acute coronary syndromes (39%), aortopathies (40%), and valvular heart disease (30%). Most respondents (76%) lack access to a dedicated cardio-obstetrics team, and only 29% of practicing cardiologists received cardio-obstetrics didactics during training. One third of fellows in training reported seeing pregnant women 0 to 1 time per year, and 12% of fellows in training report formal training in cardio-obstetrics.
Conclusions:
Formalized training in cardio-obstetrics is uncommon, and limited access to multidisciplinary cardio-obstetrics teams and large knowledge gaps exist among cardiovascular clinicians. Augmentation of cardio-obstetrics education across career stages is needed to reduce these deficits. These survey results are an initial step toward developing a standard expectation for clinicians\' training in cardio-obstetrics.




J Am Heart Assoc: 18 Apr 2022:e024229; epub ahead of print
Bello NA, Agrawal A, Davis MB, Harrington CM, ... Walsh MN, Park K
J Am Heart Assoc: 18 Apr 2022:e024229; epub ahead of print | PMID: 35435011
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Impact:
Abstract

Tissue Sodium in Patients With Early Stage Hypertension: A Randomized Controlled Trial.

Alsouqi A, Deger SM, Sahinoz M, Mambungu C, ... Harrison DG, Ikizler TA

Background:
Sodium (Na+) stored in skin and muscle tissue is associated with essential hypertension. Sodium magnetic resonance imaging is a validated method of quantifying tissue stores of Na+. In this study, we evaluated tissue Na+ in patients with elevated blood pressure or stage I hypertension in response to diuretic therapy or low Na+ diet. Methods and Results In a double-blinded, placebo-controlled trial, patients with systolic blood pressure 120 to 139 mm Hg were randomized to low sodium diet (<2 g of sodium), chlorthalidone, spironolactone, or placebo for 8 weeks. Muscle and skin Na+ using sodium magnetic resonance imaging and pulse wave velocity were assessed at the beginning and end of the study. Ninety-eight patients were enrolled to undergo baseline measurements and 54 completed randomization. Median baseline muscle and skin Na+ in 98 patients were 16.4 mmol/L (14.9, 18.9) and 13.1 mmol/L (11.1, 16.1), respectively. After 8 weeks, muscle Na+ increased in the diet and chlorthalidone arms compared with placebo. Skin sodium was decreased only in the diet arm compared with placebo. These associations remained significant after adjustment for age, sex, body mass index, systolic blood pressure, and urinary sodium. No changes were observed in pulse wave velocity among the different groups when compared with placebo.
Conclusions:
Diuretic therapy for 8 weeks did not decrease muscle or skin sodium or improve pulse wave velocity in patients with elevated blood pressure or stage I hypertension. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02236520.




J Am Heart Assoc: 18 Apr 2022:e022723; epub ahead of print
Alsouqi A, Deger SM, Sahinoz M, Mambungu C, ... Harrison DG, Ikizler TA
J Am Heart Assoc: 18 Apr 2022:e022723; epub ahead of print | PMID: 35435017
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Impact:
Abstract

Atrial Electrical Remodeling in Mice With Cardiac-Specific Overexpression of Angiotensin II Type 1 Receptor.

Demers J, Ton AT, Huynh F, Thibault S, ... Nemer M, Fiset C

Background:
Elevated angiotensin II levels are thought to play an important role in atrial electrical and structural remodeling associated with atrial fibrillation. However, the mechanisms by which this remodeling occurs are still unclear. Accordingly, we explored the effects of angiotensin II on atrial remodeling using transgenic mice overexpressing angiotensin II type 1 receptor (AT1R) specifically in cardiomyocytes. Methods and Results Voltage-clamp techniques, surface ECG, programmed electrical stimulations along with quantitative polymerase chain reaction, Western blot, and Picrosirius red staining were used to compare the atrial phenotype of AT1R mice and their controls at 50 days and 6 months. Atrial cell capacitance and fibrosis were increased only in AT1R mice at 6 months, indicating the presence of structural remodeling. Ca2+ (ICaL) and K+ currents were not altered by AT1R overexpression (AT1R at 50 days). However, ICaL density and CaV1.2 messenger RNA expression were reduced by structural remodeling (AT1R at 6 months). Conversely, Na+ current (INa) was reduced (-65%) by AT1R overexpression (AT1R at 50 days) and the presence of structural remodeling (AT1R at 6 months) yields no further effect. The reduced INa density was not explained by lower NaV1.5 expression but was rather associated with an increase in sarcolemmal protein kinase C alpha expression in the atria, suggesting that chronic AT1R activation reduced INa through protein kinase C alpha activation. Furthermore, connexin 40 expression was reduced in AT1R mice at 50 days and 6 months. These changes were associated with delayed atrial conduction time, as evidenced by prolonged P-wave duration.
Conclusions:
Chronic AT1R activation leads to slower atrial conduction caused by reduced INa density and connexin 40 expression.




J Am Heart Assoc: 18 Apr 2022:e023974; epub ahead of print
Demers J, Ton AT, Huynh F, Thibault S, ... Nemer M, Fiset C
J Am Heart Assoc: 18 Apr 2022:e023974; epub ahead of print | PMID: 35435021
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Impact:
Abstract

Pregnancy and Progression of Cardiomyopathy in Women With LMNA Genotype-Positive.

Castrini AI, Skjølsvik E, Estensen ME, Almaas VM, ... Lakdawala NK, Haugaa KH

Background:
We aimed to assess the association between number of pregnancies and long-term progression of cardiac dysfunction, arrhythmias, and event-free survival in women with pathogenic or likely pathogenic variants of gene encoding for Lamin A/C proteins ( LMNA+). Methods and Results We retrospectively included consecutive women with LMNA+ and recorded pregnancy data. We collected echocardiographic data, occurrence of atrial fibrillation, atrioventricular block, sustained ventricular arrhythmias, and implantation of cardiac electronic devices (implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator). We analyzed retrospectively complications during pregnancy and the peripartum period. We included 89 women with LMNA+ (28% probands, age 41±16 years), of which 60 had experienced pregnancy. Follow-up time was 5 [interquartile range, 3-9] years. We analyzed 452 repeated echocardiographic examinations. Number of pregnancies was not associated with increased long-term risk of atrial fibrillation, atrioventricular block, sustained ventricular arrhythmias, or implantable cardioverter defibrillator/cardiac resynchronization therapy defibrillator implantation. Women with previous pregnancy and nulliparous women had a similar annual deterioration of left ventricular ejection fraction (-0.5/year versus -0.3/year, P=0.37) and similar increase of left ventricular end-diastolic diameter (0.1/year versus 0.2/year, P=0.09). Number of pregnancies did not decrease survival free from death, left ventricular assist device, or need for cardiac transplantation. Arrhythmias occurred during 9% of pregnancies. No increase in maternal and fetal complications was observed.
Conclusions:
In our cohort of women with LMNA+, pregnancy did not seem associated with long-term adverse disease progression or event-free survival. Likewise, women with LMNA+ generally well-tolerated pregnancy, with a small proportion of patients experiencing arrhythmias.




J Am Heart Assoc: 18 Apr 2022:e024960; epub ahead of print
Castrini AI, Skjølsvik E, Estensen ME, Almaas VM, ... Lakdawala NK, Haugaa KH
J Am Heart Assoc: 18 Apr 2022:e024960; epub ahead of print | PMID: 35434999
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Impact:
Abstract

Relationship Between Age at Menopause, Obesity, and Incident Heart Failure: The Atherosclerosis Risk in Communities Study.

Ebong IA, Wilson MD, Appiah D, Michos ED, ... Chang P, Bertoni AG

Background:
The mechanisms linking menopausal age and heart failure (HF) incidence are controversial. We investigated for heterogeneity by obesity on the relationship between menopausal age and HF incidence. Methods and Results Using postmenopausal women who attended the Atherosclerosis Risk in Communities Study Visit 4, we estimated hazard ratios of incident HF associated with menopausal age using Cox proportional hazards models, testing for effect modification by obesity and adjusting for HF risk factors. Women were categorized by menopausal age: <45 years, 45 to 49 years, 50 to 54 years, and ≥55 years. Among 4441 postmenopausal women, aged 63.5±5.5 years, there were 903 incident HF events over a mean follow-up of 16.5 years. The attributable risk of generalized and central obesity for HF incidence was greatest among women who experienced menopause at age ≥55 years: 11.09/1000 person-years and 7.38/1000 person-years, respectively. There were significant interactions of menopausal age with body mass index and waist circumference for HF incidence, Pinteraction 0.02 and 0.001, respectively. The hazard ratios of incident HF for a SD increase in body mass index was elevated in women with menopausal age <45 years [1.39 (1.05-1.84)]; 45-49 years [1.33, (1.06-1.67)]; and ≥55 years [2.02, (1.41-2.89)]. The hazard ratio of incident HF for a SD increase in waist circumference was elevated only in women with menopausal age ≥55 years [2.93, (1.85-4.65)].
Conclusions:
As obesity worsened, the risk of developing HF became significantly greater when compared with women with lower body mass index and waist circumference, particularly among those who had experienced menopause at age ≥55 years.




J Am Heart Assoc: 13 Apr 2022:e024461; epub ahead of print
Ebong IA, Wilson MD, Appiah D, Michos ED, ... Chang P, Bertoni AG
J Am Heart Assoc: 13 Apr 2022:e024461; epub ahead of print | PMID: 35416049
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Impact:
Abstract

Association Between Perioperative Adverse Cardiac Events and Mortality During One-Year Follow-Up After Noncardiac Surgery.

Oh AR, Park J, Lee JH, Kim H, ... Sung JD, Lee SH

Background:
Cardiac complications are associated with perioperative mortality, but perioperative adverse cardiac events (PACEs) that are associated with long-term mortality have not been clearly defined. We identified PACE as a composite of myocardial infarction, coronary revascularization, congestive heart failure, arrhythmic attack, acute pulmonary embolism, cardiac arrest, or stroke during the 30-day postoperative period and we compared mortality according to PACE occurrence. Methods and Results From January 2011 to June 2019, a total of 203 787 consecutive adult patients underwent noncardiac surgery at our institution. After excluding those with 30-day mortality, mortality during a 1-year follow-up was compared. Machine learning with the extreme gradient boosting algorithm was also used to evaluate whether PACE was associated with 1-year mortality. After excluding 1203 patients with 30-day mortality, 202 584 patients were divided into 7994 (3.9%) patients with PACE and 194 590 (96.1%) without PACE. After an adjustment, the mortality was higher in the PACE group (2.1% versus 7.7%; hazard ratio [HR], 1.90; 95% CI, 1.74-2.09; P<0.001). Results were similar for 7839 pairs of propensity-score-matched patients (4.9% versus 7.9%; HR, 1.64; 95% CI, 1.44-1.87; P<0.001). PACE was significantly associated with mortality in the extreme gradient boostingmodel.
Conclusions:
PACE as a composite outcome was associated with 1-year mortality. Further studies are needed for PACE to be accepted as an end point in clinical studies of noncardiac surgery.




J Am Heart Assoc: 12 Apr 2022:e024325; epub ahead of print
Oh AR, Park J, Lee JH, Kim H, ... Sung JD, Lee SH
J Am Heart Assoc: 12 Apr 2022:e024325; epub ahead of print | PMID: 35411778
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Impact:
Abstract

Seizing the Window of Opportunity Within 1 Year Postpartum: Early Cardiovascular Screening.

Ackerman-Banks CM, Grechukhina O, Spatz E, Lundsberg L, ... Perley L, Lipkind HS

Background:
Our objective was to assess new chronic hypertension 6 to 12 months postpartum for those with hypertensive disorder of pregnancy (HDP) compared with normotensive participants. Methods and Results We performed a prospective cohort study of participants with singleton gestations and no known preexisting medical conditions who were diagnosed with HDP compared with normotensive women with no pregnancy complications (non-HDP). Participants underwent cardiovascular risk assessment 6 to 12 months after delivery. Primary outcome was onset of new chronic hypertension at 6 to 12 months postpartum. We also examined lipid values, metabolic syndrome, prediabetes, diabetes, and 30-year cardiovascular disease (CVD) risk. Multivariable logistic regression was performed to assess the association between HDP and odds of a postpartum diagnosis of chronic hypertension while adjusting for parity, body mass index, insurance, and family history of CVD. There were 58 participants in the HDP group and 51 participants in the non-HDP group. Baseline characteristics between groups were not statistically different. Participants in the HDP group had 4-fold adjusted odds of developing a new diagnosis of chronic hypertension 6 to 12 months after delivery, compared with those in the non-HDP group (adjusted odds ratio, 4.60 [95% CI, 1.65-12.81]), when adjusting for body mass index, parity, family history of CVD, and insurance. Of the HDP group, 58.6% (n=34) developed new chronic hypertension. Participants in the HDP group had increased estimated 30-year CVD risk and were more likely to have metabolic syndrome, a higher fasting blood glucose, and higher low-density lipoprotein cholesterol.
Conclusions:
Participants without known underlying medical conditions who develop HDP have 4-fold increased odds of new diagnosis of chronic hypertension by 6 to 12 months postpartum as well as increased 30-year CVD risk scores. Implementation of multidisciplinary care models focused on CVD screening, patient education, and lifestyle interventions during the first year postpartum may serve as an effective primary prevention strategy for the development of CVD.




J Am Heart Assoc: 12 Apr 2022:e024443; epub ahead of print
Ackerman-Banks CM, Grechukhina O, Spatz E, Lundsberg L, ... Perley L, Lipkind HS
J Am Heart Assoc: 12 Apr 2022:e024443; epub ahead of print | PMID: 35411781
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Impact:
Abstract

Cost-Effectiveness of Monitoring Patients Post-Stroke With Mobile ECG During the Hospital Stay.

Gao L, Moodie M, Freedman B, Lam C, ... Liu X, Yan B

Background:
The effectiveness of a nurse-led in-hospital monitoring protocol with mobile ECG (iECG) was investigated for detecting atrial fibrillation in patients post-ischemic stroke or post-transient ischemic attack. The study aimed to assess the cost-effectiveness of using iECG during the initial hospital stay compared with standard 24-hour Holter monitoring. Methods and Results A Markov microsimulation model was constructed to simulate the lifetime health outcomes and costs. The rate of atrial fibrillation detection in iECG and Holter monitoring during the in-hospital phase and characteristics of modeled population (ie, age, sex, CHA2DS2-VASc) were informed by patient-level data. Costs related to recurrent stroke, stroke management, medications (new oral anticoagulants), and rehabilitation were included. The cost-effectiveness analysis outcome was calculated as an incremental cost per quality-adjusted life-year gained. As results, monitoring patients with iECG post-stroke during the index hospitalization was associated with marginally higher costs (A$31 196) and greater benefits (6.70 quality-adjusted life-years) compared with 24-hour Holter surveillance (A$31 095 and 6.66 quality-adjusted life-years) over a 20-year time horizon, with an incremental cost-effectiveness ratio of $3013/ quality-adjusted life-years. Monitoring patients with iECG also contributed to lower recurrence of stroke and stroke-related deaths (140 recurrent strokes and 20 deaths avoided per 10 000 patients). The probabilistic sensitivity analyses suggested iECG is highly likely to be a cost-effective intervention (100% probability).
Conclusions:
A nurse-led iECG monitoring protocol during the acute hospital stay was found to improve the rate of atrial fibrillation detection and contributed to slightly increased costs and improved health outcomes. Using iECG to monitor patients post-stroke during initial hospitalization is recommended to complement routine care.




J Am Heart Assoc: 12 Apr 2022:e022735; epub ahead of print
Gao L, Moodie M, Freedman B, Lam C, ... Liu X, Yan B
J Am Heart Assoc: 12 Apr 2022:e022735; epub ahead of print | PMID: 35411782
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Impact:
Abstract

Establishing a National Cardiovascular Disease Surveillance System in the United States Using Electronic Health Record Data: Key Strengths and Limitations.

Williams BA, Voyce S, Sidney S, Roger VL, ... Chamberlain AM, Benziger CP
Cardiovascular disease surveillance involves quantifying the evolving population-level burden of cardiovascular outcomes and risk factors as a data-driven initial step followed by the implementation of interventional strategies designed to alleviate this burden in the target population. Despite widespread acknowledgement of its potential value, a national surveillance system dedicated specifically to cardiovascular disease does not currently exist in the United States. Routinely collected health care data such as from electronic health records (EHRs) are a possible means of achieving national surveillance. Accordingly, this article elaborates on some key strengths and limitations of using EHR data for establishing a national cardiovascular disease surveillance system. Key strengths discussed include the: (1) ubiquity of EHRs and consequent ability to create a more \"national\" surveillance system, (2) existence of a common data infrastructure underlying the health care enterprise with respect to data domains and the nomenclature by which these data are expressed, (3) longitudinal length and detail that define EHR data when individuals repeatedly patronize a health care organization, and (4) breadth of outcomes capable of being surveilled with EHRs. Key limitations discussed include the: (1) incomplete ascertainment of health information related to health care-seeking behavior and the disconnect of health care data generated at separate health care organizations, (2) suspect data quality resulting from the default information-gathering processes within the clinical enterprise, (3) questionable ability to surveil patients through EHRs in the absence of documented interactions, and (4) the challenge in interpreting temporal trends in health metrics, which can be obscured by changing clinical and administrative processes.



J Am Heart Assoc: 12 Apr 2022:e024409; epub ahead of print
Williams BA, Voyce S, Sidney S, Roger VL, ... Chamberlain AM, Benziger CP
J Am Heart Assoc: 12 Apr 2022:e024409; epub ahead of print | PMID: 35411783
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Impact:
Abstract

Nomogram for Postoperative Headache in Adult Patients Undergoing Elective Cardiac Surgery.

Wang D, Le S, Wu J, Xie F, ... Du X, Huang X

Background:
Postoperative headache (POH) is frequent after cardiac surgery; however, few studies on risk factors for POH exist. The aims of the current study were to explore risk factors related to POH after elective cardiac surgery and to establish a predictive system. Methods and Results Adult patients undergoing elective open-heart surgery under cardiopulmonary bypass from 2016 to 2020 in 4 cardiac centers were retrospectively included. Two thirds of the patients were randomly allocated to a training set and one third to a validation set. Predictors for POH were selected by univariate and multivariate analysis. POH developed in 3154 of the 13 440 included patients (23.5%) and the overall mortality rate was 2.3%. Eight independent risk factors for POH after elective cardiac surgery were identified, including female sex, younger age, smoking history, chronic headache history, hypertension, lower left ventricular ejection fraction, longer cardiopulmonary bypass time, and more intraoperative transfusion of red blood cells. A nomogram based on the multivariate model was constructed, with reasonable calibration and discrimination, and was well validated. Decision curve analysis revealed good clinical utility. Finally, 3 risk intervals were divided to better facilitate clinical application.
Conclusions:
A nomogram model for POH after elective cardiac surgery was developed and validated using 8 predictors, which may have potential application value in clinical risk assessment, decision-making, and individualized treatment associated with POH.




J Am Heart Assoc: 12 Apr 2022:e023837; epub ahead of print
Wang D, Le S, Wu J, Xie F, ... Du X, Huang X
J Am Heart Assoc: 12 Apr 2022:e023837; epub ahead of print | PMID: 35411784
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Abstract

Financial Incentives for Transcatheter Aortic Valve Implantation in Ontario, Canada: A Cost-Utility Analysis.

Peel JK, Neves Miranda R, Naimark D, Woodward G, ... Madan M, Wijeysundera HC

Background:
Transcatheter aortic valve implantation (TAVI) is a minimally invasive therapy for patients with severe aortic stenosis, which has become standard of care. The objective of this study was to determine the maximum cost-effective investment in TAVI care that should be made at a health system level to meet quality indicator goals. Methods and Results We performed a cost-utility analysis using probabilistic patient-level simulation of TAVI care from the Ontario, Canada, Ministry of Health perspective. Costs and health utilities were accrued over a 2-year time horizon. We created 4 hypothetical strategies that represented TAVI care meeting ≥1 quality indicator targets, (1) reduced wait times, (2) reduced hospital length of stay, (3) reduced pacemaker use, and (4) combined strategy, and compared these with current TAVI care. Per-person costs, quality-adjusted life years, and clinical outcomes were estimated by the model. Using these, incremental net monetary benefits were calculated for each strategy at different cost-effectiveness thresholds between $0 and $100 000 per quality-adjusted life year. Clinical improvements over the current practice were estimated with all comparator strategies. In Ontario, achieving quality indicator benchmarks could avoid ≈26 wait-list deaths and 200 wait-list hospitalizations annually. Compared with current TAVI care, the incremental net monetary benefit for this strategy varied from $10 765 (±$8721) and $17 221 (±$8977). This would translate to an annual investment of between ≈$14 to ≈$22 million by the Ontario Ministry of Health to incentivize these performance measures being cost-effective.
Conclusions:
This study has quantified the modest annual investment required and substantial clinical benefit of meeting improvement goals in TAVI care.




J Am Heart Assoc: 12 Apr 2022:e025085; epub ahead of print
Peel JK, Neves Miranda R, Naimark D, Woodward G, ... Madan M, Wijeysundera HC
J Am Heart Assoc: 12 Apr 2022:e025085; epub ahead of print | PMID: 35411786
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Abstract

Health Care Use of Cardiac Specialty Care in Children With Muscular Dystrophy in the United States.

Mejia EJ, Lin KY, Okunowo O, Iacobellis KA, ... Griffis H, Edelson JB

Background:
Duchenne and Becker muscular dystrophy are progressive disorders associated with cardiac mortality. Guidelines recommend routine surveillance; we assess cardiac resource use and identify gaps in care delivery. Methods and Results Male patients, aged 1 to 18 years, with Duchenne and Becker muscular dystrophy between January 2013 and December 2017 were identified in the IBM MarketScan Research Database. The cohort was divided into <10 and 10 to 18 years of age. The primary outcome was rate of annual health care resource per person year. Resource use was assessed for place of service, cardiac testing, and medications. Adjusted incidence rate ratios (IRRs) were estimated using a Poisson regression model. Medication use was measured by proportion of days covered. There were 1386 patients with a median follow-up time of 3.0 years (interquartile range, 1.9-4.7 years). Patients in the 10 to 18 years group had only 0.40 (95% CI, 0.35-0.45) cardiology visits per person year and 0.66 (95% CI, 0.62-0.70) echocardiography/magnetic resonance imaging per person year. Older patients had higher rates of inpatient admissions (IRR, 1.46; 95% CI, 1.03-2.09), outpatient cardiology visits (IRR, 2.0; 95% CI, 1.66-2.40), cardiac imaging (IRR, 1.59; 95% CI, 1.40-1.80), and Holter monitoring (IRR, 3.33; 95% CI, 2.35-4.73). A proportion of days covered >80% for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was observed in 13.6% (419/3083) of total person years among patients in the 10 to 18 years group.
Conclusions:
Children 10 to 18 years of age have higher rates of cardiac resource use compared with those <10 years of age. However, rates in both age groups fall short of guidelines. Opportunities exist to identify barriers to resource use and optimize cardiac care for patients with Duchenne and Becker muscular dystrophy.




J Am Heart Assoc: 12 Apr 2022:e024722; epub ahead of print
Mejia EJ, Lin KY, Okunowo O, Iacobellis KA, ... Griffis H, Edelson JB
J Am Heart Assoc: 12 Apr 2022:e024722; epub ahead of print | PMID: 35411787
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Abstract

Contextualizing National Policies Regulating Access to Low-Dose Aspirin in America and Europe Using the Full Report of a Transatlantic Patient Survey of Aspirin in Preventive Cardiology.

Jacobsen AP, Lim ZL, Chang B, Lambeth KD, ... Martin SS, McEvoy JW

Background:
Aspirin is widely administered to prevent cardiovascular disease (CVD). However, appropriate use of aspirin depends on patient understanding of its risks, benefits, and indications, especially where aspirin is available over the counter (OTC). Methods and Results We did a survey of patient-reported 10-year cardiovascular risk; aspirin therapy status; form of aspirin access (OTC versus prescription); and knowledge of the risks, benefits, and role of aspirin in CVD prevention. Consecutive adults aged ≥50 years with ≥1 cardiovascular risk factor attending outpatient clinics in America and Europe were recruited. We also systematically reviewed national policies regulating access to low-dose aspirin for CVD prevention. At each site, 150 responses were obtained (300 total). Mean±SD age was 65±10 years, 40% were women, and 41% were secondary prevention patients. More than half of the participants at both sites did not know (1) their own level of 10-year CVD risk, (2) the expected magnitude of reduction in CVD risk with aspirin, or (3) aspirin\'s bleeding risks. Only 62% of all participants reported that aspirin was routinely indicated for secondary prevention, whereas 47% believed it was routinely indicated for primary prevention (P=0.048). In America, 83.5% participants obtained aspirin OTC compared with 2.5% in Europe (P<0.001). Finally, our review of European national policies found only 2 countries where low-dose aspirin was available OTC.
Conclusions:
Many patients have poor insight into their objectively calculated 10-year cardiovascular risk and do not know the risks, benefits, and role of aspirin in CVD prevention. Aspirin is mainly obtained OTC in America in contrast to Europe, where most countries restrict access to low-dose aspirin.




J Am Heart Assoc: 12 Apr 2022:e023995; epub ahead of print
Jacobsen AP, Lim ZL, Chang B, Lambeth KD, ... Martin SS, McEvoy JW
J Am Heart Assoc: 12 Apr 2022:e023995; epub ahead of print | PMID: 35411788
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Abstract

Antiatherosclerotic Effects of CSL112 Mediated by Enhanced Cholesterol Efflux Capacity.

Kingwell BA, Nicholls SJ, Velkoska E, Didichenko SA, ... Korjian S, Gibson CM
Approximately 12% of patients with acute myocardial infarction (AMI) experience a recurrent major adverse cardiovascular event within 1 year of their primary event, with most occurring within the first 90 days. Thus, there is a need for new therapeutic approaches that address this 90-day post-AMI high-risk period. The formation and eventual rupture of atherosclerotic plaque that leads to AMI is elicited by the accumulation of cholesterol within the arterial intima. Cholesterol efflux, a mechanism by which cholesterol is removed from plaque, is predominantly mediated by apolipoprotein A-I, which is rapidly lipidated to form high-density lipoprotein in the circulation and has atheroprotective properties. In this review, we outline how cholesterol efflux dysfunction leads to atherosclerosis and vulnerable plaque formation, including inflammatory cell recruitment, foam cell formation, the development of a lipid/necrotic core, and degradation of the fibrous cap. CSL112, a human plasma-derived apolipoprotein A-I, is in phase 3 of clinical development and aims to reduce the risk of recurrent cardiovascular events in patients with AMI in the first 90 days after the index event by increasing cholesterol efflux. We summarize evidence from preclinical and clinical studies suggesting that restoration of cholesterol efflux by CSL112 can stabilize plaque by several anti-inflammatory/immune-regulatory processes. These effects occur rapidly and could stabilize vulnerable plaques in patients who have recently experienced an AMI, thereby reducing the risk of recurrent major adverse cardiovascular events in the high-risk early post-AMI period.



J Am Heart Assoc: 12 Apr 2022:e024754; epub ahead of print
Kingwell BA, Nicholls SJ, Velkoska E, Didichenko SA, ... Korjian S, Gibson CM
J Am Heart Assoc: 12 Apr 2022:e024754; epub ahead of print | PMID: 35411789
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Abstract

Evaluating the Coronary Artery Disease Consortium Model and the Coronary Artery Calcium Score in Predicting Obstructive Coronary Artery Disease in a Symptomatic Mixed Asian Cohort.

Baskaran L, Neo YP, Lee JK, Yoon YE, ... Bittencourt MS, Shaw LJ

Background:
The utility of a given pretest probability score in predicting obstructive coronary artery disease (CAD) is population dependent. Previous studies investigating the additive value of coronary artery calcium (CAC) on pretest probability scores were predominantly limited to Western populations. This retrospective study seeks to evaluate the CAD Consortium (CAD2) model in a mixed Asian cohort within Singapore with stable chest pain and to evaluate the incremental value of CAC in predicting obstructive CAD. Methods and Results Patients who underwent cardiac computed tomography and had chest pain were included. The CAD2 clinical model comprised of age, sex, symptom typicality, diabetes, hypertension, hyperlipidemia, and smoking status and was compared with the CAD2 extended model that added CAC to assess the incremental value of CAC scoring, as well as to the corresponding locally calibrated local assessment of the heart models. A total of 522 patients were analyzed (mean age 54±11 years, 43.1% female). The CAD2 clinical model obtained an area under the curve of 0.718 (95% CI, 0.668-0.767). The inclusion of CAC score improved the area under the curve to 0.896 (95% CI, 0.867-0.925) in the CAD2 models and from 0.767 (95% CI, 0.721-0.814) to 0.926 (95% CI, 0.900-0.951) in the local assessment of the heart models. The locally calibrated local assessment of the heart models showed better discriminative performance than the corresponding CAD2 models (P<0.05 for all).
Conclusions:
The CAD2 model was validated in a symptomatic mixed Asian cohort and local calibration further improved performance. CAC scoring provided significant incremental value in predicting obstructive CAD.




J Am Heart Assoc: 12 Apr 2022:e022697; epub ahead of print
Baskaran L, Neo YP, Lee JK, Yoon YE, ... Bittencourt MS, Shaw LJ
J Am Heart Assoc: 12 Apr 2022:e022697; epub ahead of print | PMID: 35411790
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Abstract

Prevalence and Outcomes of Bicuspid Aortic Valve in Patients With Aneurysmal Sub-Arachnoid Hemorrhage: A Prospective Neurology Registry Report.

Vallabhajosyula S, Yang LT, Thomas SC, Maleszewski JJ, ... Rabinstein AA, Michelena HI

Background:
Intracranial aneurysms are reported in 6%-10% of patients with bicuspid aortic valve (BAV), and routine intracranial aneurysm surveillance has been advocated by some. We assessed the prevalence and features of the most important patient-outcome: aneurysmal sub-arachnoid hemorrhage (aSAH), as compared with controls without aSAH, and tricuspid aortic valve (TAV) with aSAH. Methods and Results Adult patients with accurate diagnosis of aSAH and at least one echocardiogram between 2000 and 2019 were identified from a consecutive prospectively maintained registry of aSAH admissions. Controls without a diagnosis of SAH were age- and sex-matched. BAV prevalence was confirmed echocardiographically. Severity of aSAH was categorized using modified Fisher and World Federation of Neurological Scale. Neurologic outcome was assessed using modified Rankin score. A total 488 aSAH cases and 990 controls were identified and BAV status was confirmed. Prevalence of BAV in patients with aSAH was 1.2% (6/488) versus 3.5% (35/990) in controls, P=0.01. BAV+aSAH were noted to be younger than TAV+aSAH (56±11 versus 68±14; P=0.03) with smaller aneurysms (5±2 versus 7±4; P=0.31). The severity of aSAH was lesser in BAV+aSAH than TAV (modified Fisher grade>2 50% versus 74%; P=0.19, World Federation of Neurological Scale grade>3 17% versus 36%; P=0.43). BAV+aSAH had less severe neurologic disability (modified Rankin score 3%-6 33% versus 49% in TAV; P=0.44) and comparable in-hospital mortality rates (P=0.93). BAV had lower odds for aSAH on multivariate analysis (odds ratio 0.23[CI 0.08-0.65]; P=0.01).
Conclusions:
Prevalence of BAV was 3 times lower in the aSAH registry than in controls without aSAH. BAV+aSAH had clinically smaller aneurysms, clinically smaller bleeds, and better neurologic outcome as compared with TAV+aSAH, which needs to be confirmed in larger studies. These findings argue against routine surveillance for intracranial aneurysms in patients with BAV without aortic coarctation.




J Am Heart Assoc: 12 Apr 2022:e022339; epub ahead of print
Vallabhajosyula S, Yang LT, Thomas SC, Maleszewski JJ, ... Rabinstein AA, Michelena HI
J Am Heart Assoc: 12 Apr 2022:e022339; epub ahead of print | PMID: 35411791
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Impact:
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