Journal: J Am Heart Assoc

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Abstract

Racial Disparities in Hospitalization Among Patients Who Receive a Diagnosis of Acute Coronary Syndrome in the Emergency Department.

Islek D, Ali MK, Manatunga A, Alonso A, Vaccarino V

Background:
Timely hospitalization of patients who are diagnosed with an acute coronary syndrome (ACS) at the emergency department (ED) is a crucial step to lower the risk of ACS mortality. We examined whether there are racial and ethnic differences in the risk of being discharged home among patients who received a diagnostic code of ACS at the ED and whether having health insurance plays a role. Methods and Results We examined 51 022 910 discharge records of ED visits in Florida, New York, and Utah in the years 2008, 2011, 2014, and 2016/2017 using state-specific data from the Healthcare Cost and Utilization Project. We identified ED admissions for acute myocardial infarction or unstable angina using the International Classification of Diseases, Ninth Revision (ICD-9)/International Statistical Classification of Diseases, Tenth Revision (ICD-10) diagnostic codes. We used generalized estimating equation models to compare the risk of being discharged home across racial and ethnic groups. We used Poisson marginal structural models to estimate the mediating role of health insurance status. The proportion discharged home with a diagnostic code of ACS was 12% among Black patients, 6% among White patients, 9% among Hispanic patients, and 9% among Asian/Pacific Islander patients. The incidence risk ratio for being discharged home was 1.26 (95% CI, 1.18-1.34) in Black patients, 1.23 (95% CI, 1.15-1.32) in Hispanic patients, and 1.11 (95% CI, 0.93-1.31) in Asian/Pacific Islander patients compared with White patients. Race and ethnicity were marginally associated with discharge home via pathways not mediated by health insurance.
Conclusions:
Racial and ethnic disparities exist in the hospitalization of patients who received a diagnostic code of ACS in the ED. Possible causes need to be investigated.




J Am Heart Assoc: 21 Sep 2022:e025733; epub ahead of print
Islek D, Ali MK, Manatunga A, Alonso A, Vaccarino V
J Am Heart Assoc: 21 Sep 2022:e025733; epub ahead of print | PMID: 36129027
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Abstract

Sleep Apnea and Physical Movement During Sleep, But Not Sleep Duration, Are Independently Associated With Progression of Left Ventricular Diastolic Dysfunction: Prospective Hyogo Sleep Cardio-Autonomic Atherosclerosis Cohort Study.

Kidawara Y, Kadoya M, Morimoto A, Daimon T, ... Ishihara M, Koyama H

Background:
Although co-occurrence of sleep disorder with heart failure is known, it is not clear whether that condition is a cause or consequence of heart failure. The present study was conducted as a longitudinal examination of the predictive value of sleep parameters on progression of left ventricular diastolic dysfunction. Methods and Results Four-hundred fifty-two subjects were followed for a mean of 34.7 months. An outcome of diastolic dysfunction was defined as increase in early inflow velocity/early diastolic tissue velocity >14. Sleep apnea-hypopnea index, minimal oxygen saturation, sleep duration, and activity index (physical movement during sleep time, a potential parameter of poor sleep quality) were determined using apnomonitor and actigraphy findings, while heart rate variability was measured with a 24-hour active tracer device. Sixty-six of the patients developed diastolic dysfunction during the follow-up period, with a median time of 25 months. Kaplan-Meier analysis results revealed that those with sleep apnea classified as moderate (apnea-hypopnea index 15 to <30, P<0.01 versus none) or severe (apnea-hypopnea index ≥30, P<0.01 versus none), and with a high activity index (Q3 or Q4, P<0.01 versus Q1), but not short sleep duration (P=0.27) had a significantly greater risk for a diastolic dysfunction event. Results of multivariable Cox proportional hazards regression analysis indicated that moderate to severe sleep apnea after a follow-up period of 3 years (hazard ratio [HR], 9.26 [95% CI, 1.89-45.26], P<0.01) and high activity index (HR, 1.85 [95% CI, 1.01-3.39], P=0.04) were significantly and independently associated with future diastolic dysfunction. Moreover, significant association of high activity index with the outcome was not confounded by either minimal oxygen saturation or heart rate variability.
Conclusions:
Sleep apnea and physical movement during sleep, but not sleep duration and autonomic nervous dysfunction, are independent important predictors for progression of left ventricular diastolic dysfunction.




J Am Heart Assoc: 21 Sep 2022:e024948; epub ahead of print
Kidawara Y, Kadoya M, Morimoto A, Daimon T, ... Ishihara M, Koyama H
J Am Heart Assoc: 21 Sep 2022:e024948; epub ahead of print | PMID: 36129028
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Abstract

Comparison of Bolus Dosing of Methohexital and Propofol in Elective Direct Current Cardioversion.

Beaty EH, Fernando RJ, Jacobs ML, Winter GG, ... Bhave PD, Royster RL

Background:
Methohexital and propofol can both be used as sedation for direct current cardioversion (DCCV). However, there are limited data comparing these medications in this setting. We hypothesized that patients receiving methohexital for elective DCCV would be sedated more quickly, recover from sedation faster, and experience less adverse effects. Methods and Results This was a prospective, blinded randomized controlled trial conducted at a single academic medical center. Eligible participants were randomly assigned to receive either methohexital (0.5 mg/kg) or propofol (0.8 mg/kg) as a bolus for elective DCCV. The times from bolus of the medication to achieving a Ramsay Sedation Scale score of 5 to 6, first shock, eyes opening on command, and when the patient could state their age and name were obtained. The need for additional medication dosing, airway intervention, vital signs, and medication side effects were also recorded. Seventy patients who were randomized to receive methohexital (n=37) or propofol (n=33) were included for analysis. The average doses of methohexital and propofol were 0.51 mg/kg and 0.84 mg/kg, respectively. There were no significant differences between methohexital and propofol in the time from end of injection to loss of conscious (1.4±1.8 versus 1.1±0.5 minutes; P=0.33) or the time to first shock (1.7±1.9 versus 1.4±0.5 minutes; P=0.31). Time intervals were significantly lower for methohexital compared with propofol in the time to eyes opening on command (5.1±2.5 versus 7.8±3.7 minutes; P=0.0005) as well as at the time to the ability to answer simple questions of age and name (6.0±2.6 versus 8.6±4.0 minutes; P=0.001). The methohexital group experienced less hypotension (8.1% versus 42.4%; P<0.001) and less hypoxemia (0.0% versus 15.2%; P=0.005), had lower need for jaw thrust/chin lift (16.2% versus 42.4%; P=0.015), and had less pain on injection compared with propofol using the visual analog scale (7.2±9.7 versus 22.4±28.1; P=0.003).
Conclusions:
In this model of fixed bolus dosing, methohexital was associated with faster recovery, more stable hemodynamics, and less hypoxemia after elective DCCV compared with propofol. It can be considered as a preferred agent for sedation for DCCV. Registration URL: https://www.clinicaltrials.gov/ct; Unique identifier: NCT04187196.




J Am Heart Assoc: 21 Sep 2022:e026198; epub ahead of print
Beaty EH, Fernando RJ, Jacobs ML, Winter GG, ... Bhave PD, Royster RL
J Am Heart Assoc: 21 Sep 2022:e026198; epub ahead of print | PMID: 36129031
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Abstract

Intravenous Thrombolysis With Alteplase at 0.6 mg/kg in Patients With Ischemic Stroke Taking Direct Oral Anticoagulants.

Okada T, Yoshimoto T, Wada S, Yoshimura S, ... Takashima H, Koga M

Background:
We elucidated the safety of treatment with alteplase at 0.6 mg/kg within 24 hours for patients on direct oral anticoagulants (DOACs) before ischemic stroke onset. Methods and Results Consecutive patients with acute ischemic stroke who underwent intravenous thrombolysis using alteplase at 0.6 mg/kg from 2011 to 2021 were enrolled from our single-center prospective stroke registry. We compared outcomes between patients taking DOACs and those not taking oral anticoagulants within 48 hours of stroke onset. The primary safety outcome was the rate of symptomatic intracranial hemorrhage with a ≥4-point increase on the National Institutes of Health Stroke Scale score from baseline. The efficacy outcome was defined as 3-month modified Rankin Scale score of 0 to 2 after stroke onset. Of 915 patients with acute ischemic stroke who received intravenous thrombolysis (358 women; median age, 76 years; median National Institutes of Health Stroke Scale score, 10), 40 patients took DOACs (6 took dabigatran, 8 took rivaroxaban, 16 took apixaban, and 10 took edoxaban) within 24 hours of onset and 753 patients did not take any oral anticoagulants. The rate of symptomatic intracranial hemorrhage was comparable between patients on DOACs and those not on oral anticoagulants (2.5% versus 2.4%, P=0.95). The rate of favorable outcomes was comparable between the 2 groups (59.4% versus 58.2%, P=0.46), although the admission National Institutes of Health Stroke Scale score was higher in patients on DOACs. No significant differences showed in any intracranial hemorrhage within 36 hours or mortality at 3 months.
Conclusions:
Intravenous thrombolysis would be safely performed for patients on DOACs following the recommendations of the Japanese guidelines. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02251665.




J Am Heart Assoc: 21 Sep 2022:e025809; epub ahead of print
Okada T, Yoshimoto T, Wada S, Yoshimura S, ... Takashima H, Koga M
J Am Heart Assoc: 21 Sep 2022:e025809; epub ahead of print | PMID: 36129032
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Abstract

Lowering Uric Acid May Improve Prognosis in Patients With Hyperuricemia and Heart Failure With Preserved Ejection Fraction.

Nishino M, Egami Y, Kawanami S, Sugae H, ... Sakata Y, Osaka CardioVascular Conference (OCVC)‐Heart Failure Investigators *

Background:
An association between uric acid (UA) and cardiovascular diseases, including heart failure (HF), has been reported. However, whether UA is a causal risk factor for HF is controversial. In particular, the prognostic value of lowering UA in patients with HF with preserved ejection fraction (HFpEF) is unclear. Methods and Results We enrolled patients with HFpEF from the PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients With Heart Failure With Preserved Ejection Fraction) registry. We investigated whether UA was correlated with the composite events, including all-cause mortality and HF rehospitalization, in patients with hyperuricemia and HFpEF (UA >7.0 mg/dL). Additionally, we evaluated whether lowering UA for 1 year (≥1.0 mg/dL) in them reduced mortality or HF rehospitalization. We finally analyzed 464 patients with hyperuricemia. In multivariable Cox regression analysis, UA was an independent determinant of composite death and rehospitalization (hazard ratio [HR], 1.15 [95% CI, 1.03-1.27], P=0.015). We divided them into groups with severe and mild hyperuricemia according to median estimated value of serum UA (8.3 mg/dL). Cox proportional hazards models revealed the incidence of all-cause mortality was significantly higher in the group with severe hyperuricemia than in the group with mild hyperuricemia (HR, 1.73 [95% CI, 1.19-2.25], P=0.004). The incidence of all-cause mortality was significantly decreased in the group with lowering UA compared with the group with nonlowering UA (HR, 1.71 [95% CI, 1.02-2.86], P=0.041). The incidence of urate-lowering therapy tended to be higher in the group with lowering UA than in the group with nonlowering UA (34.9% versus 24.6%, P=0.06).
Conclusions:
UA is a predictor for the composite of all-cause death and HF rehospitalization in patients with hyperuricemia and HFpEF. In these patients, lowering UA, including the use of urate-lowering therapy, may improve prognosis.




J Am Heart Assoc: 21 Sep 2022:e026301; epub ahead of print
Nishino M, Egami Y, Kawanami S, Sugae H, ... Sakata Y, Osaka CardioVascular Conference (OCVC)‐Heart Failure Investigators *
J Am Heart Assoc: 21 Sep 2022:e026301; epub ahead of print | PMID: 36129035
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Abstract

Evaluating the Cardiovascular Risk in an Aging Population of People With HIV: The Impact of Hepatitis C Virus Coinfection.

Lang R, Humes E, Hogan B, Lee J, ... Triant VA, Althoff KN

Background:
People with HIV (PWH) are at an increased risk of cardiovascular disease (CVD) with an unknown added impact of hepatitis C virus (HCV) coinfection. We aimed to identify whether HCV coinfection increases the risk of type 1 myocardial infarction (T1MI) and if the risk differs by age. Methods and Results We used data from NA-ACCORD (North American AIDS Cohort Collaboration on Research and Design) from January 1, 2000, to December 31, 2017, PWH (aged 40-79 years) who had initiated antiretroviral therapy. The primary outcome was an adjudicated T1MI event. Those who started direct-acting HCV antivirals were censored at the time of initiation. Crude incidence rates per 1000 person-years were calculated for T1MI by calendar time. Discrete time-to-event analyses with complementary log-log models were used to estimate adjusted hazard ratios and 95% CIs for T1MI among those with and without HCV. Among 23 361 PWH, 4677 (20%) had HCV. There were 89 (1.9%) T1MIs among PWH with HCV and 314 (1.7%) among PWH without HCV. HCV was not associated with increased T1MI risk in PWH (adjusted hazard ratio, 0.98 [95% CI, 0.74-1.30]). However, the risk of T1MI increased with age and was amplified in those with HCV (adjusted hazard ratio per 10-year increase in age, 1.85 [95% CI, 1.38-2.48]) compared with those without HCV (adjusted hazard ratio per 10-year increase in age,1.30 [95% CI, 1.13-1.50]; P<0.001, test of interaction).
Conclusions:
HCV coinfection was not significantly associated with increased T1MI risk; however, the risk of T1MI with increasing age was greater in those with HCV compared with those without, and HCV status should be considered when assessing CVD risk in aging PWH.




J Am Heart Assoc: 21 Sep 2022:e026473; epub ahead of print
Lang R, Humes E, Hogan B, Lee J, ... Triant VA, Althoff KN
J Am Heart Assoc: 21 Sep 2022:e026473; epub ahead of print | PMID: 36129038
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Abstract

Association Between the Affordable Care Act Medicaid Expansion and Receipt of Cardiac Resynchronization Therapy by Race and Ethnicity.

Mwansa H, Barry I, Knapp SM, Mazimba S, ... Sweitzer NK, Breathett K

Background:
Black and Hispanic patients are less likely to receive cardiac resynchronization therapy (CRT) than White patients. Medicaid expansion has been associated with increased access to cardiovascular care among racial and ethnic groups with higher prevalence of underinsurance. It is unknown whether the Medicaid expansion was associated with increased receipt of CRT by race and ethnicity. Methods and Results Using Healthcare Cost and Utilization Project Data State Inpatient Databases from 19 states and Washington, DC, we analyzed 1061 patients from early-adopter states (Medicaid expansion by January 2014) and 745 patients from nonadopter states (no implementation 2013-2014). Estimates of change in census-adjusted rates of CRT with or without defibrillator by race and ethnicity and Medicaid adopter status 1 year before and after January 2014 were conducted using a quasi-Poisson regression model. Following the Medicaid expansion, the rate of CRT did not significantly change among Black individuals from early-adopter states (1.07 [95% CI, 0.78-1.48]) or nonadopter states (0.79 [95% CI, 0.57-1.09]). There were no significant changes in rates of CRT among Hispanic individuals from early-adopter states (0.99 [95% CI, 0.70-1.38]) or nonadopter states (1.01 [95% CI, 0.65-1.57]). There was a 34% increase in CRT rates among White individuals from early-adopter states (1.34 [95% CI, 1.05-1.70]), and no significant change among White individuals from nonadopter states (0.77 [95% CI, 0.59-1.02]). The change in CRT rates among White individuals was associated with the timing of the Medicaid implementation (P=0.003).
Conclusions:
Among states participating in Healthcare Cost and Utilization Project Data State Inpatient Databases, implementation of Medicaid expansion was associated with increase in CRT rates among White individuals residing in states that adopted the Medicaid expansion policy. Further work is needed to address disparities in CRT among Black and Hispanic patients.




J Am Heart Assoc: 21 Sep 2022:e026766; epub ahead of print
Mwansa H, Barry I, Knapp SM, Mazimba S, ... Sweitzer NK, Breathett K
J Am Heart Assoc: 21 Sep 2022:e026766; epub ahead of print | PMID: 36129039
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Abstract

Gait in Cerebral Amyloid Angiopathy.

Sharma B, Gee M, Nelles K, Cox E, ... Camicioli R, Smith EE

Background:
Gait is a complex task requiring coordinated efforts of multiple brain networks. To date, there is little evidence on whether gait is altered in cerebral amyloid angiopathy (CAA). We aimed to identify impairments in gait performance and associations between gait impairment and neuroimaging markers of CAA, cognition, and falls. Methods and Results Gait was assessed using the Zeno Walkway during preferred pace and dual task walks, and grouped into gait domains (Rhythm, Pace, Postural Control, and Variability). Participants underwent neuropsychological testing and neuroimaging. Falls and fear of falling were assessed through self-report questionnaires. Gait domain scores were standardized and analyzed using linear regression adjusting for age, sex, height, and other covariates. Participants were patients with CAA (n=29), Alzheimer disease with mild dementia (n=16), mild cognitive impairment (n=24), and normal elderly controls (n=47). CAA and Alzheimer disease had similarly impaired Rhythm, Pace, and Variability, and higher dual task cost than normal controls or mild cognitive impairment. Higher Pace score was associated with better global cognition, processing speed, and memory. Gait measures were not correlated with microbleed count or white matter hyperintensity volume. Number of falls was not associated with gait domain scores, but participants with low fear of falling had higher Pace (odds ratio [OR], 2.61 [95% CI, 1.59-4.29]) and lower Variability (OR, 1.64 [95% CI, 1.10-2.44]).
Conclusions:
CAA is associated with slower walking, abnormal rhythm, and greater gait variability than in healthy controls. Future research is needed to identify the mechanisms underlying gait impairments in CAA, and whether they predict future falls.




J Am Heart Assoc: 21 Sep 2022:e025886; epub ahead of print
Sharma B, Gee M, Nelles K, Cox E, ... Camicioli R, Smith EE
J Am Heart Assoc: 21 Sep 2022:e025886; epub ahead of print | PMID: 36129041
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Abstract

Comprehensive Cardiovascular Magnetic Resonance-Derived Myocardial Strain Analysis Provides Independent Prognostic Value in Acute Myocarditis.

Vos JL, Raafs AG, van der Velde N, Germans T, ... Heymans SRB, Nijveldt R

Background:
Late gadolinium enhancement and left ventricular (LV) ejection fraction on cardiovascular magnetic resonance (CMR) are prognostic markers, but their predictive value for incident heart failure or life-threatening arrhythmias in acute myocarditis patients is limited. CMR-derived feature tracking provides a more sensitive analysis of myocardial function and may improve risk stratification in myocarditis. In this study, the prognostic value of LV, right ventricular, and left atrial strain in acute myocarditis patients is evaluated. Methods and Results In this multicenter retrospective study, patients with CMR-proven acute myocarditis were included. The primary end point was occurrence of major adverse cardiovascular events: all-cause mortality, heart transplantation, heart failure hospitalizations, and life threatening arrhythmias. LV global longitudinal strain, global circumferential strain and global radial strain, right ventricular-global longitudinal strain and left atrial strain were measured. Unadjusted and adjusted cox proportional hazard regression analysis were performed. In total, 162 CMR-proven myocarditis patients were included (41 ± 17 years, 75% men). Mean LV ejection fraction was 51 ± 12%, and 144 (89%) patients had presence of late gadolinium enhancement. Major adverse cardiovascular events occurred in 29 (18%) patients during a follow-up of 5.5 (2.2-8.3) years. All LV strain parameters were independent predictors of outcome beyond clinical features, LV ejection fraction and late gadolinium enhancement (LV-global longitudinal strain: hazard ratio [HR] 1.07, P=0.02; LV-global circumferential strain: HR 1.15, P=0.02; LV-global radial strain: HR 0.98, P=0.03), but right ventricular or left atrial strain did not predict outcome.
Conclusions:
CMR-derived LV strain analysis provides independent prognostic value on top of clinical parameters, LV ejection fraction and late gadolinium enhancement in acute myocarditis patients, while left atrial and right ventricular strain seem to be of less importance.




J Am Heart Assoc: 21 Sep 2022:e025106; epub ahead of print
Vos JL, Raafs AG, van der Velde N, Germans T, ... Heymans SRB, Nijveldt R
J Am Heart Assoc: 21 Sep 2022:e025106; epub ahead of print | PMID: 36129042
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Abstract

Longitudinal Adherence to Diabetes Quality Indicators and Cardiac Disease: A Nationwide Population-Based Historical Cohort Study of Patients With Pharmacologically Treated Diabetes.

Abdel-Rahman N, Calderon-Margalit R, Cohen A, Elran E, ... Ben-Yehuda A, Manor O

Background:
Evidence of the cardiovascular benefits of adherence to quality indicators in diabetes care over a period of years is lacking. Methods and Results We conducted a population-based, historical cohort study of 105 656 people aged 45 to 80 with pharmacologically treated diabetes and who were free of cardiac disease in 2010. Data were retrieved from electronic medical records of the 4 Israeli health maintenance organizations. The association between level of adherence to national quality indicators (2006-2010: adherence assessment) and incidence of cardiac outcome; ischemic heart disease or heart failure (2011-2016: outcome assessment) was estimated using Cox proportional hazards models. During 529 551 person-years of follow-up, 19 246 patients experienced cardiac disease. An inverse dose-response association between the level of adherence and risk of cardiac morbidity was shown for most of the quality indicators. The associations were modified by age, with stronger associations among younger patients (<65 years). Low adherence to low-density lipoprotein cholesterol testing (≤2 years) during the first 5 years was associated with 41% increased risk of cardiac morbidity among younger patients. Patients who had uncontrolled low-density lipoprotein cholesterol in all first 5 years had hazard ratios of 1.60 (95% CI, 1.49-1.72) and 1.23 (95% CI, 1.14-1.32), among patients aged <65 and ≥65 years, respectively, compared with those who achieved target level. Patients who failed to achieve target levels of glycated hemoglobin or blood pressure had an increased risk (hazard ratios, 1.50-1.69) for cardiac outcomes.
Conclusions:
Longitudinal adherence to quality indicators in diabetes care is associated with reduced risk of cardiac morbidity. Implementation of programs that measure and enhance quality of care may improve the health outcomes of people with diabetes.




J Am Heart Assoc: 21 Sep 2022:e025603; epub ahead of print
Abdel-Rahman N, Calderon-Margalit R, Cohen A, Elran E, ... Ben-Yehuda A, Manor O
J Am Heart Assoc: 21 Sep 2022:e025603; epub ahead of print | PMID: 36129044
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Abstract

Deferral of Coronary Revascularization in Patients With Reduced Ejection Fraction Based on Physiological Assessment: Impact on Long-Term Survival.

Gallinoro E, Paolisso P, Di Gioia G, Bermpeis K, ... De Bruyne B, Barbato E

Background:
Deferring revascularization in patients with nonsignificant stenoses based on fractional flow reserve (FFR) is associated with favorable clinical outcomes up to 15 years. Whether this holds true in patients with reduced left ventricular ejection fraction is unclear. We aimed to investigate whether FFR provides adjunctive clinical benefit compared with coronary angiography in deferring revascularization of patients with intermediate coronary stenoses and reduced left ventricular ejection fraction. Methods and Results Consecutive patients with reduced left ventricular ejection fraction (≤50%) undergoing coronary angiography between 2002 and 2010 were screened. We included patients with at least 1 intermediate coronary stenosis (diameter stenosis ≥40%) in whom revascularization was deferred based either on angiography plus FFR (FFR guided) or angiography alone (angiography guided). The primary end point was the cumulative incidence of all-cause death at 10 years. The secondary end point (incidence of major adverse cardiovascular and cerebrovascular events) was a composite of all-cause death, myocardial infarction, any revascularization, and stroke. A total of 840 patients were included (206 in the FFR-guided group and 634 in the angiography-guided group). Median follow-up was 7 years (interquartile range, 3.22-11.08 years). After 1:1 propensity-score matching, baseline characteristics between the 2 groups were similar. All-cause death was significantly lower in the FFR-guided group compared with the angiography-guided group (94 [45.6%] versus 119 [57.8%]; hazard ratio [HR], 0.65 [95% CI, 0.49-0.85]; P<0.01). The rate of major adverse cardiovascular and cerebrovascular events was lower in the FFR-guided group (123 [59.7%] versus 139 [67.5%]; HR, 0.75 [95% CI, 0.59-0.95]; P=0.02).
Conclusions:
In patients with reduced left ventricular ejection fraction, deferring revascularization of intermediate coronary stenoses based on FFR is associated with a lower incidence of death and major adverse cardiovascular and cerebrovascular events at 10 years.




J Am Heart Assoc: 21 Sep 2022:e026656; epub ahead of print
Gallinoro E, Paolisso P, Di Gioia G, Bermpeis K, ... De Bruyne B, Barbato E
J Am Heart Assoc: 21 Sep 2022:e026656; epub ahead of print | PMID: 36129045
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Abstract

Myocardial Work in Patients Hospitalized With COVID-19: Relation to Biomarkers, COVID-19 Severity, and All-Cause Mortality.

Olsen FJ, Lassen MCH, Skaarup KG, Christensen J, ... Remme EW, Biering-Sørensen T

Background:
COVID-19 infection has been hypothesized to affect left ventricular function; however, the underlying mechanisms and the association to clinical outcome are not understood. The global work index (GWI) is a novel echocardiographic measure of systolic function that may offer insights on cardiac dysfunction in COVID-19. We hypothesized that GWI was associated with disease severity and all-cause death in patients with COVID-19. Methods and Results In a multicenter study of patients admitted with COVID-19 (n=305), 249 underwent pressure-strain loop analyses to quantify GWI at a median time of 4 days after admission. We examined the association of GWI to cardiac biomarkers (troponin and NT-proBNP [N-terminal pro-B-type natriuretic peptide]), disease severity (oxygen requirement and CRP [C-reactive protein]), and all-cause death. Patients with elevated troponin (n=71) exhibited significantly reduced GWI (1508 versus 1707 mm Hg%; P=0.018). A curvilinear association to NT-proBNP was observed, with increasing NT-proBNP once GWI decreased below 1446 mm Hg%. Moreover, GWI was significantly associated with a higher oxygen requirement (relative increase of 6% per 100-mm Hg% decrease). No association was observed with CRP. Of the 249 patients, 37 died during follow-up (median, 58 days). In multivariable Cox regression, GWI was associated with all-cause death (hazard ratio, 1.08 [95% CI, 1.01-1.15], per 100-mm Hg% decrease), but did not increase C-statistics when added to clinical parameters.
Conclusions:
In patients admitted with COVID-19, our findings indicate that NT-proBNP and troponin may be associated with lower GWI, whereas CRP is not. GWI was independently associated with all-cause death, but did not provide prognostic information beyond readily available clinical parameters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04377035.




J Am Heart Assoc: 21 Sep 2022:e026571; epub ahead of print
Olsen FJ, Lassen MCH, Skaarup KG, Christensen J, ... Remme EW, Biering-Sørensen T
J Am Heart Assoc: 21 Sep 2022:e026571; epub ahead of print | PMID: 36129046
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Abstract

Feasibility of Quantitative Flow Ratio Virtual Stenting for Guidance of Serial Coronary Lesions Intervention.

Guan S, Gan Q, Han W, Zhai X, ... Tu S, Qu X

Background:
Coronary physiology measurement in serial coronary lesions with multiple stenoses is challenging. Therefore, we evaluated the feasibility of Murray fractal law-based quantitative flow ratio (μQFR) virtual stenting for guidance of serial coronary lesions intervention. Methods and Results Patients who underwent elective coronary angiography and had 2 serial de novo coronary lesions of 30% to 90% diameter stenosis by visual estimation were prospectively enrolled. μQFR and fractional flow reserve (FFR) were assessed after coronary angiography. In vessels with an FFR ≤0.80, the lesion with the larger pressure gradient was considered to be the primary lesion and treated firstly, followed by FFR measurement. The second lesion was stented when FFR ≤0.80. All μQFR and predicted μQFR after stenting were calculated from diagnostic coronary angiography before interventions, with the analysts masked to the FFR data. A total of 54 patients with 61 target vessels were interrogated. Percutaneous coronary intervention was performed in 44 vessels with FFR ≤0.80. After stenting the primary lesions, 14 nonprimary lesions had FFR ≤0.80 and a second drug-eluting stent was implanted. There was excellent correlation (r=0.97, P<0.001) and good agreement (mean difference: 0.00±0.03) between baseline μQFR and FFR in identifying flow-limiting lesions. Per-vessel diagnostic accuracy of μQFR on de novo lesions was 96.7% (95% CI, 88.7%-99.6%). μQFR and FFR are highly consistent (93.2%) in identifying the primary lesion requiring revascularization. After stenting the primary lesions, per-vessel diagnostic accuracy of predicted μQFR for identifying the significance of the nonprimary lesion was 90.9%. Predicted residual μQFR with virtual stenting was higher than final FFR (mean difference: 0.05±0.06).
Conclusions:
In vessels with serial coronary lesions, virtual stenting by μQFR can identify the primary flow-limiting lesion for revascularization.




J Am Heart Assoc: 21 Sep 2022:e025663; epub ahead of print
Guan S, Gan Q, Han W, Zhai X, ... Tu S, Qu X
J Am Heart Assoc: 21 Sep 2022:e025663; epub ahead of print | PMID: 36129050
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Abstract

Coronary Artery Perforations: Glasgow Natural History Study of Covered Stent Coronary Interventions (GNOCCI) Study.

Ford TJ, Adamson C, Morrow AJ, Rocchiccioli P, ... Oldroyd KG, McEntegart M

Background:
The objective of the GNOCCI (Glasgow Natural History Study of Covered Stent Coronary Interventions) Study was to report the incidence and outcomes of coronary artery perforations over an 18-year period at a single, high-volume percutaneous coronary intervention center. We considered both the temporal trends and long-term outcomes of covered stent deployment. Methods and Results We evaluated procedural and long-term clinical outcomes following coronary perforation in a cohort of 43,343 consecutive percutaneous coronary intervention procedures. Procedural major adverse cardiac events were defined as a composite of death, myocardial infarction, stroke, target vessel revascularization, or cardiac surgery within 24 hours. A total of 161 (0.37%) procedures were complicated by coronary perforation of which 57 (35%) were Ellis grade III. Incidence increased with time over the study period (r=0.73; P<0.001). Perforation severity was linearly associated with procedural mortality (median 2.9-year follow-up): Ellis I (0%), Ellis II (1.7%), Ellis III/IIIB (21%), P<0.001. Procedural major adverse cardiac events occurred in 47% of patients with Ellis III/IIIB versus 13.5% of those with Ellis I/II perforations (odds ratio, 5.8; 95% CI, 2.7-12.5; P<0.001). Covered stents were associated with an increased risk of stent thrombosis at 2.9-year follow-up (Academic Research Consortium definite or probable; 9.1% versus 0.9%; risk ratio, 10.5; 95% CI, 1.1-97; P=0.04).
Conclusions:
The incidence of coronary perforation increased between 2001 and 2019. Severe perforation was associated with higher procedural major adverse cardiac events and was an independent predictor of long-term mortality. Although covered stents are a potentially lifesaving treatment, the generation of devices used during the study period was limited by their efficacy and high risk of stent thrombosis. Registration Information Clinicaltrials.gov. Identifier: NCT03862352.




J Am Heart Assoc: 21 Sep 2022:e024492; epub ahead of print
Ford TJ, Adamson C, Morrow AJ, Rocchiccioli P, ... Oldroyd KG, McEntegart M
J Am Heart Assoc: 21 Sep 2022:e024492; epub ahead of print | PMID: 36129052
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Impact:
Abstract

Determining the Likelihood of Disease Pathogenicity Among Incidentally Identified Genetic Variants in Rare Dilated Cardiomyopathy-Associated Genes.

Yang Q, Berkman AM, Ezekian JE, Rosamilia M, ... Liu P, Landstrom AP

Background:
As utilization of clinical exome sequencing (ES) has expanded, criteria for evaluating the diagnostic weight of incidentally identified variants are critical to guide clinicians and researchers. This is particularly important in genes associated with dilated cardiomyopathy (DCM), which can cause heart failure and sudden death. We sought to compare the frequency and distribution of incidentally identified variants in DCM-associated genes between a clinical referral cohort with those in control and known case cohorts to determine the likelihood of pathogenicity among those undergoing genetic testing for non-DCM indications. Methods and Results A total of 39 rare, non-TTN DCM-associated genes were identified and evaluated from a clinical ES testing referral cohort (n=14 005, Baylor Genetic Laboratories) and compared with a DCM case cohort (n=9442) as well as a control cohort of population variants (n=141 456) derived from the gnomAD database. Variant frequencies in each cohort were compared. Signal-to-noise ratios were calculated comparing the DCM and ES cohort with the gnomAD cohort. The likely pathogenic/pathogenic variant yield in the DCM cohort (8.2%) was significantly higher than in the ES cohort (1.9%). Based on signal-to-noise and correlation analysis, incidental variants found in FLNC, RBM20, MYH6, DSP, ABCC9, JPH2, and NEXN had the greatest chance of being DCM-associated.
Conclusions:
The distribution of pathogenic variants between the ES cohort and the DCM case cohort was gene specific, and variants found in the ES cohort were similar to variants found in the control cohort. Incidentally identified variants in specific genes are more associated with DCM than others.




J Am Heart Assoc: 21 Sep 2022:e025257; epub ahead of print
Yang Q, Berkman AM, Ezekian JE, Rosamilia M, ... Liu P, Landstrom AP
J Am Heart Assoc: 21 Sep 2022:e025257; epub ahead of print | PMID: 36129056
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Impact:
Abstract

Loss of Rbl2 (Retinoblastoma-Like 2) Exacerbates Myocardial Ischemia/Reperfusion Injury.

Chen J, Xia P, Liu Y, Kogan C, Cheng Z

Background:
The postmitotic state of adult cardiomyocytes, maintained by the cell cycle repressor Rbl2 (retinoblastoma-like 2), is associated with considerable resistance to apoptosis. However, whether Rbl2 regulates cardiomyocyte apoptosis remains unknown. Methods and Results Here, we show that ablation of Rbl2 increased cardiomyocyte apoptosis following acute myocardial ischemia/reperfusion injury, leading to diminished cardiac function and exaggerated ventricular remodeling in the long term. Mechanistically, ischemia/reperfusion induced expression of the proapoptotic protein BCL2 interacting protein 3 (Bnip3), which was augmented by deletion of Rbl2. Because the Bnip3 promoter contains an adenoviral early region 2 binding factor (E2F)-binding site, we further showed that loss of Rbl2 upregulated the transcriptional activator E2F1 but downregulated the transcriptional repressor E2F4. In cultured cardiomyocytes, treatment with H2O2 markedly increased the levels of E2F1 and Bnip3, resulting in mitochondrial depolarization and apoptosis. Depletion of Rbl2 significantly augmented H2O2-induced mitochondrial damage and apoptosis in vitro.
Conclusions:
Rbl2 deficiency enhanced E2F1-mediated Bnip3 expression, resulting in aggravated cardiomyocyte apoptosis and ischemia/reperfusion injury. Our results uncover a novel antiapoptotic role for Rbl2 in cardiomyocytes, suggesting that the cell cycle machinery may directly regulate apoptosis in postmitotic cardiomyocytes. These findings may be exploited to develop new strategies to limit ischemia/reperfusion injury in the treatment of acute myocardial infarction.




J Am Heart Assoc: 21 Sep 2022:e024764; epub ahead of print
Chen J, Xia P, Liu Y, Kogan C, Cheng Z
J Am Heart Assoc: 21 Sep 2022:e024764; epub ahead of print | PMID: 36129061
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Impact:
Abstract

Insulin Resistance Is Associated With Heart Failure With Recovered Ejection Fraction in Patients Without Diabetes.

Yang CD, Pan WQ, Feng S, Quan JW, ... Zhang RY, Wang XQ

Background:
Because of advances in medical treatments, a substantial proportion of patients with heart failure (HF) have experienced recovery of ejection fraction (EF), termed HF with recovered EF (HFrecEF). Insulin resistance (IR) is prevalent in HF and tightly related with prognosis. This study investigates the relationship between IR and the incidence of HFrecEF in patients who are nondiabetic. Methods and Results A total of 262 patients with HF with reduced EF (HFrEF) who were nondiabetic were consecutively enrolled. Patients were classified into HFrecEF (follow-up EF>40% and ≥10% absolute increase) or otherwise persistent HFrEF based on repeat echocardiograms after 12 months. IR was estimated by an updated homeostasis model assessment for IR (HOMA2-IR). The median HOMA2-IR level was 1.05 (interquartile range [IQR], 0.67-1.63) in our cohort of patients with HF who were nondiabetic. During follow-up, 121 (odds ratio [OR], 46.2% [95% CI 40.2-52.2]) patients developed HFrecEF. Compared with patients with HFrEF, patients with HFrecEF had significantly lower HOMA2-IR levels (0.92 [IQR, 0.61-1.37] versus 1.14 [IQR, 0.75-1.78], P=0.007), especially in nonischemic HF. Log2-transformed HOMA2-IR was inversely correlated to improvements in EF (Pearson\'s r=-0.25, P<0.001). After multivariable adjustment, a doubling of HOMA2-IR was associated with a 42.8% decreased likelihood of HFrecEF (OR, 0.572 [95% CI, 0.385-0.827]).
Conclusions:
This study reveals that IR is independently associated with compromised development of HFrecEF in patients who are nondiabetic.




J Am Heart Assoc: 21 Sep 2022:e026184; epub ahead of print
Yang CD, Pan WQ, Feng S, Quan JW, ... Zhang RY, Wang XQ
J Am Heart Assoc: 21 Sep 2022:e026184; epub ahead of print | PMID: 36129062
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Impact:
Abstract

Outcomes Following Acute Coronary Syndrome in Patients With and Without Rheumatic Immune-Mediated Inflammatory Diseases.

Wassif H, Saad M, Desai R, Hajj-Ali RA, ... Desai M, Mentias A

Background:
Rheumatic immune mediated inflammatory diseases (IMIDs) are associated with high risk of acute coronary syndrome. The long-term prognosis of acute coronary syndrome in patients with rheumatic IMIDs is not well studied. Methods and Results We identified Medicare beneficiaries admitted with a primary diagnosis of myocardial infarction (MI) from 2014 to 2019. Outcomes of patients with MI and concomitant rheumatic IMIDs including systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, dermatomyositis, or psoriasis were compared with propensity matched control patients without rheumatic IMIDs. One-to-three propensity-score matching was done for exact age, sex, race, ST-segment-elevation MI, and non-ST-segment-elevation MI variables and greedy approach on other comorbidities. The study primary outcome was all-cause mortality. The study cohort included 1 654 862 patients with 3.6% prevalence of rheumatic IMIDs, the most common of which was rheumatoid arthritis, followed by systemic lupus erythematosus. Patients with rheumatic IMIDs were younger, more likely to be women, and more likely to present with non-ST-segment-elevation MI. Patients with rheumatic IMIDs were less likely to undergo coronary angiography, percutaneous coronary intervention or coronary artery bypass grafting. After propensity-score matching, at median follow up of 24 months (interquartile range 9-45), the risk of mortality (adjusted hazard ratio [HR], 1.15 [95% CI, 1.14-1.17]), heart failure (HR, 1.12 [95% CI 1.09-1.14]), recurrent MI (HR, 1.08 [95% CI 1.06-1.11]), and coronary reintervention (HR, 1.06 [95% CI, 1.01-1.13]) (P<0.05 for all) was higher in patients with versus without rheumatic IMIDs.
Conclusions:
Patients with MI and rheumatic IMIDs have higher risk of mortality, heart failure, recurrent MI, and need for coronary reintervention during follow-up compared with patients without rheumatic IMIDs.




J Am Heart Assoc: 14 Sep 2022:e026411; epub ahead of print
Wassif H, Saad M, Desai R, Hajj-Ali RA, ... Desai M, Mentias A
J Am Heart Assoc: 14 Sep 2022:e026411; epub ahead of print | PMID: 36102221
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Impact:
Abstract

Sulfonylurea Is Associated With Higher Risks of Ventricular Arrhythmia or Sudden Cardiac Death Compared With Metformin: A Population-Based Cohort Study.

Lee TTL, Hui JMH, Lee YHA, Satti DI, ... Cheng SH, Tse G

Background:
Commonly prescribed diabetic medications such as metformin and sulfonylurea may be associated with different arrhythmogenic risks. This study compared the risk of ventricular arrhythmia or sudden cardiac death between metformin and sulfonylurea users in patients with type 2 diabetes. Methods and Results Patients aged ≥40 years who were diagnosed with type 2 diabetes or prescribed antidiabetic agents in Hong Kong between January 1, 2009, and December 31, 2009, were included and followed up until December 31, 2019. Patients prescribed with both metformin and sulfonylurea or had prior myocardial infarction were excluded. The study outcome was a composite of ventricular arrhythmia or sudden cardiac death. Metformin users and sulfonylurea users were matched at a 1:1 ratio by propensity score matching. The matched cohort consisted of 16 596 metformin users (47.70% men; age, 68±11 years; mean follow-up, 4.92±2.55 years) and 16 596 sulfonylurea users (49.80% men; age, 70±11 years; mean follow-up, 4.93±2.55 years). Sulfonylurea was associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin hazard ratio (HR, 1.90 [95% CI, 1.73-2.08]). Such difference was consistently observed in subgroup analyses stratifying for insulin usage or known coronary heart disease.
Conclusions:
Sulfonylurea use is associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin in patients with type 2 diabetes.




J Am Heart Assoc: 14 Sep 2022:e026289; epub ahead of print
Lee TTL, Hui JMH, Lee YHA, Satti DI, ... Cheng SH, Tse G
J Am Heart Assoc: 14 Sep 2022:e026289; epub ahead of print | PMID: 36102222
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Impact:
Abstract

Enriching the American Heart Association COVID-19 Cardiovascular Disease Registry Through Linkage With External Data Sources: Rationale and Design.

Oseran AS, Sun T, Wadhera RK, Dahabreh IJ, ... Yeh RW, Kazi DS

Background:
The AHA Registry (American Heart Association COVID-19 Cardiovascular Disease Registry) captures detailed information on hospitalized patients with COVID-19. The registry, however, does not capture information on social determinants of health or long-term outcomes. Here we describe the linkage of the AHA Registry with external data sources, including fee-for-service (FFS) Medicare claims, to fill these gaps and assess the representativeness of linked registry patients to the broader Medicare FFS population hospitalized with COVID-19. Methods and Results We linked AHA Registry records of adults ≥65 years from March 2020 to September 2021 with Medicare FFS claims using a deterministic linkage algorithm and with the American Hospital Association Annual Survey, Rural Urban Commuting Area codes, and the Social Vulnerability Index using hospital and geographic identifiers. We compared linked individuals with unlinked FFS beneficiaries hospitalized with COVID-19 to assess the representativeness of the AHA Registry. A total of 10 010 (47.0%) records in the AHA Registry were successfully linked to FFS Medicare claims. Linked and unlinked FFS beneficiaries were similar with respect to mean age (78.1 versus 77.9, absolute standardized difference [ASD] 0.03); female sex (48.3% versus 50.2%, ASD 0.04); Black race (15.1% versus 12.0%, ASD 0.09); dual-eligibility status (26.1% versus 23.2%, ASD 0.07); and comorbidity burden. Linked patients were more likely to live in the northeastern United States (35.7% versus 18.2%, ASD 0.40) and urban/metropolitan areas (83.9% versus 76.8%, ASD 0.18). There were also differences in hospital-level characteristics between cohorts. However, in-hospital outcomes were similar (mortality, 23.3% versus 20.1%, ASD 0.08; home discharge, 45.5% versus 50.7%, ASD 0.10; skilled nursing facility discharge, 24.4% versus 22.2%, ASD 0.05).
Conclusions:
Linkage of the AHA Registry with external data sources such as Medicare FFS claims creates a unique and generalizable resource to evaluate long-term health outcomes after COVID-19 hospitalization.




J Am Heart Assoc: 14 Sep 2022:e7743; epub ahead of print
Oseran AS, Sun T, Wadhera RK, Dahabreh IJ, ... Yeh RW, Kazi DS
J Am Heart Assoc: 14 Sep 2022:e7743; epub ahead of print | PMID: 36102226
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Impact:
Abstract

Impact of Socioeconomic Status on Mortality and Readmission in Patients With Heart Failure With Reduced Ejection Fraction: The ARIC Study.

Mathews L, Ding N, Mok Y, Shin JI, ... Coresh J, Matsushita K

Background:
Low socioeconomic status (SES) is associated with a higher risk of heart failure (HF). The contribution of individual and neighborhood SES to the prognosis and quality of care for HF with reduced ejection fraction is not clear yet has important implications. Methods and Results We examined 728 participants of the ARIC (Atherosclerosis Risk in Communities) study (mean age, 78.2 years; 34% Black participants; 46% women) hospitalized with HF with reduced ejection fraction (ejection fraction <50%) between 2005 and 2018. We assessed associations between education, income, and area deprivation index with mortality and HF readmission using multivariable Cox models. We also evaluated the use of guideline-directed medical therapy (optimal: ≥3 of ß-blockers, mineralocorticoid receptor antagonist, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers; acceptable: at least 2) at discharge. During a median follow-up of 3.2 years, 58.7% were readmitted with HF, and 74.0% died. Low income was associated with higher mortality (hazard ratio [HR], 1.52 [95% CI, 1.14-2.04]) and readmission (HR, 1.45 [95% CI, 1.04-2.03]). Similarly, low education was associated with mortality (HR, 1.27 [95% CI, 1.01-1.59]) and readmission (HR, 1.62 [95% CI, 1.24-2.12]). The highest versus lowest area deprivation index quartile was associated with readmission (HR, 1.69 [95% CI, 1.11-2.58]) but not necessarily with mortality. The prevalence of optimal guideline-directed medical therapy and acceptable guideline-directed medical therapy was 5.5% and 54.4%, respectively, but did not significantly differ by SES.
Conclusions:
Among patients hospitalized with HF with reduced ejection fraction, low SES was independently associated with mortality and HF readmission. A targeted secondary prevention approach that focuses intensive efforts on patients with low SES will be necessary to improve outcomes of those with HF with reduced ejection fraction.




J Am Heart Assoc: 14 Sep 2022:e024057; epub ahead of print
Mathews L, Ding N, Mok Y, Shin JI, ... Coresh J, Matsushita K
J Am Heart Assoc: 14 Sep 2022:e024057; epub ahead of print | PMID: 36102228
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Impact:
Abstract

To Modify or Not to Modify: Allele-Specific Effects of 3\'UTR- Single Nucleotide Polymorphisms on Clinical Phenotype in a Long QT 1 Founder Population Segregating a Dominant-Negative Mutation.

Winbo A, Diamant UB, Persson J, Jensen SM, Rydberg A

Background:
There are conflicting reports with regard to the allele-specific gene suppression effects of single nucleotide polymorphisms (SNPs) in the 3\'untranslated region (3\'UTR) of the KCNQ1 gene in long QT syndrome type 1 (LQT1) populations. Here we assess the allele-specific effects of 3 previously published 3\'UTR-KCNQ1\'s SNPs in a LQT1 founder population segregating a dominant-negative mutation. Methods and Results Bidirectional sequencing of the KCNQ1\'s 3\'UTR was performed in the p.Y111C founder population (n=232, 147 genotype positive), with a minor allele frequency of 0.1 for SNP1 (rs2519184) and 0.6 for linked SNP2 (rs8234) and SNP3 (rs107980). Allelic phase was assessed in trios aided by haplotype data, revealing a high prevalence of derived SNP2/3 in cis with p.Y111C (89%). Allele-specific association analyses, corrected using a relatedness matrix, were performed between 3\'UTR-KCNQ1 SNP genotypes and clinical phenotypes. SNP1 in trans was associated with a significantly higher proportion of symptomatic phenotype compared with no derived SNP1 allele in trans (58% versus 32%, corrected P=0.027). SNP2/3 in cis was associated with a significantly lower proportion of symptomatic phenotype compared with no derived SNP2/3 allele in cis (32% versus 69%, corrected P=0.010).
Conclusions:
Allele-specific modifying effects on symptomatic phenotype of 3\'UTR-KCNQ1 SNPs rs2519184, rs8234, and rs107980 were seen in a LQT1 founder population segregating a dominant-negative mutation. The high prevalence of suppressive 3\'UTR-KCNQ1 SNPs segregating with the founder mutation could contribute to the previously documented low incidence of cardiac events in heterozygous carriers of the p.Y111C KCNQ1 mutation.




J Am Heart Assoc: 14 Sep 2022:e025981; epub ahead of print
Winbo A, Diamant UB, Persson J, Jensen SM, Rydberg A
J Am Heart Assoc: 14 Sep 2022:e025981; epub ahead of print | PMID: 36102229
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Impact:
Abstract

Patients With Larger Left Atrial Appendage Orifice Presented Worse Prognosis Contributed by Acute Heart Failure After Left Atrial Appendage Closure.

Ren Z, Zheng Y, Zhang J, Yang H, ... Xu Y, Zhao D

Background:
Left atrial appendage (LAA) closure (LAAC) could prevent stroke in patients with atrial fibrillation. However, LAAC may impair the compliance of the left atrium and result in poor prognosis. This study aimed to comparatively evaluate the prognosis of LAAC among patients with different sizes of LAA orifice. Methods and Results Three hundred two consecutive patients who underwent successful LAAC were included and divided into 4 groups based on LAA orifice size that was measured using transesophageal echocardiography. Clinical outcomes including thromboembolic events, major cardiocerebrovascular adverse events, and acute heart failure (AHF) were compared among 4 quartile groups and between propensity-score matched groups of large and small LAAs. Through follow-up of 39.6±8.4 months, survival of thromboembolic events was similar. Survival of major cardiocerebrovascular adverse events was significantly lower in the group with the largest LAA orifice (log-rank P<0.001), including a higher incidence of AHF with New York Heart Association class III to IV (21.4%, log-rank P=0.009). A large LAA orifice (by cutoff) could predict major cardiocerebrovascular adverse events (hazard ratio, 3.749 [95% CI, 2.074-6.779]) in most patients, except for subgroups of those aged <65 years, with paroxysmal atrial fibrillation, and/or with failed rhythm/rate control. Further compared with a propensity-score matched small-LAA group, the large-LAA orifice group still presented worse survival of AHF with New York Heart Association class III to IV (log-rank P=0.010).
Conclusions:
Patients with a larger LAA orifice presented a worse prognosis after LAAC, including a higher incidence of AHF. A large LAA orifice could predict a post-LAAC AHF event in most patients, except for young patients, patients with paroxysmal atrial fibrillation, and/or with failed rhythm/rate control. Registration URL: clinicaltrials.gov; Unique identifier: NCT04185142.




J Am Heart Assoc: 14 Sep 2022:e026309; epub ahead of print
Ren Z, Zheng Y, Zhang J, Yang H, ... Xu Y, Zhao D
J Am Heart Assoc: 14 Sep 2022:e026309; epub ahead of print | PMID: 36102232
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Impact:
Abstract

Sex Differences and Utility of Treadmill Testing in Long-QT Syndrome.

Yee LA, Han HC, Davies B, Pearman CM, ... Seifer C, Krahn AD

Background:
Diagnosis of congenital long-QT syndrome (LQTS) is complicated by phenotypic ambiguity, with a frequent normal-to-borderline resting QT interval. A 3-step algorithm based on exercise response of the corrected QT interval (QTc) was previously developed to diagnose patients with LQTS and predict subtype. This study evaluated the 3-step algorithm in a population that is more representative of the general population with LQTS with milder phenotypes and establishes sex-specific cutoffs beyond the resting QTc. Methods and Results We identified 208 LQTS likely pathogenic or pathogenic KCNQ1 or KCNH2 variant carriers in the Canadian NLQTS (National Long-QT Syndrome) Registry and 215 unaffected controls from the HiRO (Hearts in Rhythm Organization) Registry. Exercise treadmill tests were analyzed across the 5 stages of the Bruce protocol. The predictive value of exercise ECG characteristics was analyzed using receiver operating characteristic curve analysis to identify optimal cutoff values. A total of 78% of male carriers and 74% of female carriers had a resting QTc value in the normal-to-borderline range. The 4-minute recovery QTc demonstrated the best predictive value for carrier status in both sexes, with better LQTS ascertainment in female patients (area under the curve, 0.90 versus 0.82), with greater sensitivity and specificity. The optimal cutoff value for the 4-minute recovery period was 440 milliseconds for male patients and 450 milliseconds for female patients. The 1-minute recovery QTc had the best predictive value in female patients for differentiating LQTS1 versus LQTS2 (area under the curve, 0.82), and the peak exercise QTc had a marginally better predictive value in male patients for subtype with (area under the curve, 0.71). The optimal cutoff value for the 1-minute recovery period was 435 milliseconds for male patients and 455 milliseconds for femal patients.
Conclusions:
The 3-step QT exercise algorithm is a valid tool for the diagnosis of LQTS in a general population with more frequent ambiguity in phenotype. The algorithm is a simple and reliable method for the identification and prediction of the 2 major genotypes of LQTS.




J Am Heart Assoc: 14 Sep 2022:e025108; epub ahead of print
Yee LA, Han HC, Davies B, Pearman CM, ... Seifer C, Krahn AD
J Am Heart Assoc: 14 Sep 2022:e025108; epub ahead of print | PMID: 36102233
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Impact:
Abstract

Time-Dependent Risk of Cardiovascular Events Following an Exacerbation in Patients With Chronic Obstructive Pulmonary Disease: Post Hoc Analysis From the IMPACT Trial.

Dransfield MT, Criner GJ, Halpin DMG, Han MK, ... Wise R, Kunisaki KM

Background:
The association between chronic obstructive pulmonary disease exacerbations and increased cardiovascular event risk has not been adequately studied in a heterogenous population with both low and high cardiovascular risk. Methods and Results This post hoc analysis of the IMPACT (Informing the Pathway of COPD Treatment) trial (N=10 355 symptomatic patients with chronic obstructive pulmonary disease at risk of exacerbations) evaluated time-dependent risk of cardiovascular adverse events of special interest (CVAESI) following exacerbations and impact of exacerbation history, cardiovascular risk factors, and study treatment on this association. Risk (time-to-first) of CVAESI or CVAESI resulting in hospitalization or death was assessed during and 1 to 30, 31 to 90, and 91 to 365 days after resolution of moderate or severe exacerbations. CVAESI risk was compared between the period before and during/after exacerbation. CVAESI risk increased significantly during a moderate (hazard ratio [HR], 2.63 [95% CI, 2.08-3.32]) or severe (HR, 21.84 [95% CI, 17.71-26.93]) exacerbation and remained elevated for 30 days following an exacerbation (moderate: HR, 1.63 [95% CI, 1.28-2.08]; severe: HR, 1.75 [95% CI, 0.99-3.11; nonsignificant]) and decreased over time, returning to baseline by 90 days. Risk of CVAESI resulting in hospitalization or death also increased during an exacerbation (moderate: HR, 2.46 [95% CI, 1.53-3.97]; severe: HR, 41.29 [95% CI, 30.43-56.03]) and decreased in a similar time-dependent pattern. Results were consistent regardless of exacerbation history, cardiovascular risk at screening, or study treatment.
Conclusions:
Overall risk of cardiovascular events was higher during and in the 30 days following chronic obstructive pulmonary disease exacerbations, even among those with low cardiovascular risk, highlighting the need for exacerbation prevention and vigilance for cardiovascular events following exacerbations. Registration URL: https://clinicaltrials.gov/ct2/show/NCT02164513; Unique identifier: NCT02164513.




J Am Heart Assoc: 14 Sep 2022:e024350; epub ahead of print
Dransfield MT, Criner GJ, Halpin DMG, Han MK, ... Wise R, Kunisaki KM
J Am Heart Assoc: 14 Sep 2022:e024350; epub ahead of print | PMID: 36102236
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Impact:
Abstract

Modeling the Cost and Health Impacts of Diagnostic Strategies in Patients with Suspected Transthyretin Cardiac Amyloidosis.

Ge Y, Pandya A, Cuddy SAM, Singh A, Singh A, Dorbala S

Background:
Transthyretin cardiac amyloidosis (ATTR-CMP) is an increasingly recognized and treatable cause of heart failure with preserved ejection fraction. Multimodality cardiac imaging is recommended for ATTR-CMP diagnosis, but its cost-effectiveness in current clinical practice has not been well studied. Methods and Results Using a microsimulation model, we compared the cost-effectiveness of a combination of strategies involving 99mtechnetium pyrophosphate (PYP), cardiac magnetic resonance imaging, and endomyocardial biopsy for the diagnosis of ATTR-CMP. We developed a decision analytic model to project health care costs and lifetime quality-adjusted life years for symptomatic, older patients who present with congestive heart failure, with an increased left ventricular wall thickness and a 13% prevalence of ATTR-CMP. Rates of clinical events, costs, and quality-of-life values were estimated from published literature. The analysis was conducted from a US health care system perspective with health and cost outcomes discounted annually at 3%. In the base-case scenario, using a fixed tafamidis price of $16 000 annually (previously identified cost-effective price), total health care costs per person were lowest for the PYP-only strategy ($209 415) and highest for endomyocardial biopsy strategy ($215 881). Of the 7 strategies examined, the PYP-only strategy had the highest net monetary benefit using a willingness-to-pay threshold of $100 000/quality-adjusted life year. Results were sensitive to variations in model inputs for PYP and cardiac magnetic resonance imaging specificity, cost of tafamidis, and willingness-to-pay thresholds.
Conclusions:
Our model-based analyses showed that a PYP-only strategy to diagnose ATTR-CMP is the most cost-effective strategy, at willingness-to-pay threshold of $100 000/quality-adjusted life year. At higher threshold ($150 000/quality-adjusted life year), sequential tests involving PYP and cardiac magnetic resonance imaging may be considered cost effective.




J Am Heart Assoc: 14 Sep 2022:e026308; epub ahead of print
Ge Y, Pandya A, Cuddy SAM, Singh A, Singh A, Dorbala S
J Am Heart Assoc: 14 Sep 2022:e026308; epub ahead of print | PMID: 36102240
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Impact:
Abstract

Acute Impact of Fine Particulate Air Pollution on Cardiac Arrhythmias in a Population-Based Sample of Adolescents: The Penn State Child Cohort.

He F, Yanosky JD, Fernandez-Mendoza J, Chinchilli VM, ... Bixler EO, Liao D

Background:
Fine particulate (fine particles with aerodynamic diameters ≤2.5 μm [PM2.5]) exposure has been associated with a risk of cardiac arrhythmias in adults. However, the association between PM2.5 exposure and cardiac arrhythmias in adolescents remains unclear. Methods and Results To investigate the association and time course between PM2.5 exposure with cardiac arrhythmias in adolescents, we analyzed the data collected from 322 adolescents who participated in the PSCC (Penn State Child Cohort) follow-up examination. We obtained individual-level 24-hour PM2.5 concentrations with a nephelometer. Concurrent with the PM2.5 measure, we obtained 24-hour ECG data using a Holter monitor, from which cardiac arrhythmias, including premature atrial contractions and premature ventricular contractions (PVCs), were identified. PM2.5 concentration and numbers of premature atrial contractions/PVCs were summarized into 30-minute-based segments. Polynomial distributed lag models within a framework of a negative binomial model were used to assess the effect of PM2.5 concentration on numbers of premature atrial contractions and PVCs. PM2.5 exposure was associated with an acute increase in number of PVCs. Specifically, a 10 μg/m3 increase in PM2.5 concentration was associated with a 2% (95% CI, 0.4%-3.3%) increase in PVC counts 0.5 to 1.0, 1.0 to 1.5, and 1.5 to 2.0 hours after the exposure. Cumulatively, a 10 μg/m3 increment in PM2.5 was associated with a 5% (95% CI, 1%-10%) increase in PVC counts within 2 hours after exposure. PM2.5 concentration was not associated with premature atrial contraction.
Conclusions:
PM2.5 exposure was associated with an acute increased number of ventricular arrhythmias in a population-based sample of adolescents. The time course of the effect of PM2.5 on ventricular arrhythmia is within 2 hours after exposure.




J Am Heart Assoc: 14 Sep 2022:e026370; epub ahead of print
He F, Yanosky JD, Fernandez-Mendoza J, Chinchilli VM, ... Bixler EO, Liao D
J Am Heart Assoc: 14 Sep 2022:e026370; epub ahead of print | PMID: 36102241
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Impact:
Abstract

Wearable Seismocardiography-Based Assessment of Stroke Volume in Congenital Heart Disease.

Ganti VG, Gazi AH, An S, Srivatsa AV, ... Inan OT, Tandon A

Background:
Patients with congenital heart disease (CHD) are at risk for the development of low cardiac output and other physiologic derangements, which could be detected early through continuous stroke volume (SV) measurement. Unfortunately, existing SV measurement methods are limited in the clinic because of their invasiveness (eg, thermodilution), location (eg, cardiac magnetic resonance imaging), or unreliability (eg, bioimpedance). Multimodal wearable sensing, leveraging the seismocardiogram, a sternal vibration signal associated with cardiomechanical activity, offers a means to monitoring SV conveniently, affordably, and continuously. However, it has not been evaluated in a population with significant anatomical and physiological differences (ie, children with CHD) or compared against a true gold standard (ie, cardiac magnetic resonance). Here, we present the feasibility of wearable estimation of SV in a diverse CHD population (N=45 patients). Methods and Results We used our chest-worn wearable biosensor to measure baseline ECG and seismocardiogram signals from patients with CHD before and after their routine cardiovascular magnetic resonance imaging, and derived features from the measured signals, predominantly systolic time intervals, to estimate SV using ridge regression. Wearable signal features achieved acceptable SV estimation (28% error with respect to cardiovascular magnetic resonance imaging) in a held-out test set, per cardiac output measurement guidelines, with a root-mean-square error of 11.48 mL and R2 of 0.76. Additionally, we observed that using a combination of electrical and cardiomechanical features surpassed the performance of either modality alone.
Conclusions:
A convenient wearable biosensor that estimates SV enables remote monitoring of cardiac function and may potentially help identify decompensation in patients with CHD.




J Am Heart Assoc: 14 Sep 2022:e026067; epub ahead of print
Ganti VG, Gazi AH, An S, Srivatsa AV, ... Inan OT, Tandon A
J Am Heart Assoc: 14 Sep 2022:e026067; epub ahead of print | PMID: 36102243
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Impact:
Abstract

Intact Fibroblast Growth Factor 23 Regulates Chronic Kidney Disease-Induced Myocardial Fibrosis by Activating the Sonic Hedgehog Signaling Pathway.

Li L, Gan H

Background:
Clinically, myocardial fibrosis is one of the most common complications caused by chronic kidney disease (CKD). However, the potential mechanisms of CKD-induced myocardial fibrosis have not been clarified. Methods and Results In our in vivo study, a rat model of CKD with 5/6 nephrectomy was established. The CKD model was treated with the glioma 1 (Gli-1) inhibitor GANT-61, and myocardial fibrosis and serum intact fibroblast growth factor 23 levels were assessed 16 weeks after nephrectomy. Finally, we found that Gli-1 and Smoothened in the Sonic Hedgehog (Shh) signaling pathway were activated and that collagen-1 and collagen-3, which constitute the fibrotic index, were expressed in CKD myocardial tissue. After administering the Gli-1 inhibitor GANT-61, the degree of myocardial fibrosis was reduced, and Gli-1 expression was also inhibited. We also measured blood pressure, cardiac biomarkers, and other indicators in rats and performed hematoxylin-eosin staining of myocardial tissue. Furthermore, in vitro studies showed that intact fibroblast growth factor 23 promoted cardiac fibroblast proliferation and transdifferentiation into myofibroblasts by activating the Shh signaling pathway, thereby promoting cardiac fibrosis, as manifested by increased expression of the Shh, Patch 1, and Gli-1 mRNAs and Shh, Smoothened, and Gli-1 proteins in the Shh signaling pathway. The protein and mRNA levels of other fibrosis indicators, such as α-smooth muscle actin, which are also markers of transdifferentiation, collagen-1, and collagen-3, were increased.
Conclusions:
On the basis of these results, intact fibroblast growth factor 23 promotes CKD-induced myocardial fibrosis by activating the Shh signaling pathway.




J Am Heart Assoc: 14 Sep 2022:e026365; epub ahead of print
Li L, Gan H
J Am Heart Assoc: 14 Sep 2022:e026365; epub ahead of print | PMID: 36102251
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Impact:
Abstract

Health Care Usage Among Adolescents With Congenital Heart Defects at 5 Sites in the United States, 2011 to 2013.

Lui GK, Sommerhalter K, Xi Y, Botto LD, ... Soim A, Book WM

Background:
We sought to characterize health care usage for adolescents with congenital heart defects (CHDs) using population-based multisite surveillance data. Methods and Results Adolescents aged 11 to 18 years with ≥1 CHD-related diagnosis code and residing in 5 US sites were identified in clinical and administrative data sources for the years 2011 to 2013. Sites linked data on all inpatient, emergency department (ED), and outpatient visits. Multivariable log-binomial regression models including age, sex, unweighted Charlson comorbidity index, CHD severity, cardiology visits, and insurance status, were used to identify associations with inpatient, ED, and outpatient visits. Of 9626 eligible adolescents, 26.4% (n=2543) had severe CHDs and 21.4% had Charlson comorbidity index >0. At least 1 inpatient, ED, or outpatient visit was reported for 21%, 25%, and 96% of cases, respectively. Cardiology visits, cardiac imaging, cardiac procedures, and vascular procedures were reported for 38%, 73%, 10%, and 5% of cases, respectively. Inpatient, ED, and outpatient visits were consistently higher for adolescents with severe CHDs compared with nonsevere CHDs. Adolescents with severe and nonsevere CHDs had higher health care usage compared with the 2011 to 2013 general adolescent US population. Adolescents with severe CHDs versus nonsevere CHDs were twice as likely to have at least 1 inpatient visit when Charlson comorbidity index was low (Charlson comorbidity index =0). Adolescents with CHDs and public insurance, compared with private insurance, were more likely to have inpatient (adjusted prevalence ratio, 1.5 [95% CI, 1.3-1.7]) and ED (adjusted prevalence ratio, 1.6 [95% CI, 1.4-1.7]) visits.
Conclusions:
High resource usage by adolescents with CHDs indicates a substantial burden of disease, especially with public insurance, severe CHDs, and more comorbidities.




J Am Heart Assoc: 14 Sep 2022:e026172; epub ahead of print
Lui GK, Sommerhalter K, Xi Y, Botto LD, ... Soim A, Book WM
J Am Heart Assoc: 14 Sep 2022:e026172; epub ahead of print | PMID: 36102252
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Impact:
Abstract

Plasma Human Cartilage Glycoprotein-39 Is Associated With the Prognosis of Acute Ischemic Stroke.

Xu T, Zhang K, Zhong C, Zhu Z, ... Lu Y, Zhang Y

Background:
To evaluate the prognostic value of plasma YKL-40 (human cartilage glycoprotein-39) for acute ischemic stroke. Methods and Results We measured plasma YKL-40 levels in 3377 participants from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). Study outcome data on death, major disability (modified Rankin Scale score ≥3), and vascular diseases were collected at 3 months after stroke onset. The primary outcome was defined as a combination of death and major disability. During the 3-month follow-up, 828 participants (24.5%) experienced major disability or died. After multivariate adjustment, the highest YKL-40 quartile was associated with an increased risk of the primary outcome (odds ratio, 1.426 [95% CI, 1.105-1.839]; Ptrend=0.01) compared with the lowest quartile. Each SD increase in log-transformed YKL-40 level was associated with a 15.5% (95% CI, 5.6-26.3%) increased risk of the primary outcome. The multivariable-adjusted spline regression models showed a linear dose-response relationship between YKL-40 and clinical outcomes. Adding YKL-40 to a model containing conventional risk factors significantly improved the reclassification power for the primary outcome (net reclassification improvement: 15.61%, P<0.001; integrated discrimination index: 0.37%, P=0.004) and marginally significantly improved the discriminatory power for the primary outcome (area under the receiver operating characteristic curve improved by 0.003, P=0.099).
Conclusions:
A higher YKL-40 level in the acute phase of ischemic stroke was associated with an increased risk of mortality and major disability at 3 months after stroke, indicating that YKL-40 may play an important role as a prognostic marker of ischemic stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.




J Am Heart Assoc: 14 Sep 2022:e026263; epub ahead of print
Xu T, Zhang K, Zhong C, Zhu Z, ... Lu Y, Zhang Y
J Am Heart Assoc: 14 Sep 2022:e026263; epub ahead of print | PMID: 36102255
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Impact:
Abstract

Assessment of Cardiac, Vascular, and Pulmonary Pathobiology In Vivo During Acute COVID-19.

Alam SR, Vinayak S, Shah A, Doolub G, ... Chung MH, Shah ASV

Background:
Acute COVID-19-related myocardial, pulmonary, and vascular pathology and how these relate to each other remain unclear. To our knowledge, no studies have used complementary imaging techniques, including molecular imaging, to elucidate this. We used multimodality imaging and biochemical sampling in vivo to identify the pathobiology of acute COVID-19. Specifically, we investigated the presence of myocardial inflammation and its association with coronary artery disease, systemic vasculitis, and pneumonitis. Methods and Results Consecutive patients presenting with acute COVID-19 were prospectively recruited during hospital admission in this cross-sectional study. Imaging involved computed tomography coronary angiography (identified coronary disease), cardiac 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography/computed tomography (identified vascular, cardiac, and pulmonary inflammatory cell infiltration), and cardiac magnetic resonance (identified myocardial disease) alongside biomarker sampling. Of 33 patients (median age 51 years, 94% men), 24 (73%) had respiratory symptoms, with the remainder having nonspecific viral symptoms. A total of 9 patients (35%, n=9/25) had cardiac magnetic resonance-defined myocarditis. Of these patients, 53% (n=5/8) had myocardial inflammatory cell infiltration. A total of 2 patients (5%) had elevated troponin levels. Cardiac troponin concentrations were not significantly higher in patients with and without myocarditis (8.4 ng/L [interquartile range, IQR: 4.0-55.3] versus 3.5 ng/L [IQR: 2.5-5.5]; P=0.07) or myocardial cell infiltration (4.4 ng/L [IQR: 3.4-8.3] versus 3.5 ng/L [IQR: 2.8-7.2]; P=0.89). No patients had obstructive coronary artery disease or vasculitis. Pulmonary inflammation and consolidation (percentage of total lung volume) was 17% (IQR: 5%-31%) and 11% (IQR: 7%-18%), respectively. Neither were associated with the presence of myocarditis.
Conclusions:
Myocarditis was present in a third patients with acute COVID-19, and the majority had inflammatory cell infiltration. Pneumonitis was ubiquitous, but this inflammation was not associated with myocarditis. The mechanism of cardiac pathology is nonischemic and not attributable to a vasculitic process. Registration URL: https://www.isrctn.com; Unique identifier: ISRCTN12154994.




J Am Heart Assoc: 14 Sep 2022:e026399; epub ahead of print
Alam SR, Vinayak S, Shah A, Doolub G, ... Chung MH, Shah ASV
J Am Heart Assoc: 14 Sep 2022:e026399; epub ahead of print | PMID: 36102258
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Impact:
Abstract

Rates of Elective Percutaneous Coronary Intervention in England and Wales: Impact of COURAGE and ORBITA Trials.

Rashid M, Stevens C, Wijeysundera HC, Curzen N, ... Ludman PF, Mamas MA

Background:
There are limited data about how COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) and ORBITA (Objective Randomized Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) trials have impacted percutaneous coronary intervention (PCI) practices at regional or national level. We evaluated temporal trends in elective PCI rates for stable angina and, specifically, examined the impact of the COURAGE and ORBITA trials on PCI practices in England and Wales. Methods and Results We used national PCI data comprising >1.2 million patients undergoing PCI between January 2006 and December 2019. Patient demographics, procedural details, and clinical outcomes were analyzed, and temporal trends in PCI rates for stable angina were compared before and after the publication of the COURAGE and ORBITA trials. Of 1 245 802 PCI procedures, 430 248 (34.5%) were performed for stable angina. Over the study period, the number of elective PCI procedures per year (30 823 in 2006 to 34 103 in 2019) and per 100 000 population estimates (50.7 in 2006 to 58.4 in 2019) remained stable. The proportion of patients undergoing elective PCI without angina symptoms almost doubled from 5.1% to 9.7%. The incidence rate of elective PCI volume after the COURAGE trial, published in 2007, was not different from before the trial was published (incidence rate ratio, 1.06 [95% CI, 0.69-1.62]). It also remained stable after the publication of the ORBITA trial in 2017 (incidence rate ratio, 0.96 [95% CI, 0.74-1.23]).
Conclusions:
In this nationwide analysis, rates of elective PCI for stable angina remained stable over 14 years. Publication of the COURAGE and ORBITA trials had no impact on elective PCI activity.




J Am Heart Assoc: 14 Sep 2022:e025426; epub ahead of print
Rashid M, Stevens C, Wijeysundera HC, Curzen N, ... Ludman PF, Mamas MA
J Am Heart Assoc: 14 Sep 2022:e025426; epub ahead of print | PMID: 36102261
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Impact:
Abstract

Contemporary National Patterns of Eligibility and Use of Novel Lipid-Lowering Therapies in the United States.

Shen M, Aghajani Nargesi A, Nasir K, Bhatt DL, Khera R

Background:
The emergence of PCSK9i (proprotein convertase subtilisin kexin type 9 inhibitor) and icosapent ethyl (IPE) has expanded the role of lipid-lowering therapies beyond statins. Despite recommendations by clinical practice guidelines, their national eligibility and use rates remain unclear. Methods and Results In the National Health and Nutrition Examination Survey data from 2017 to 2020, we assessed eligibility and the use of statins, PCSK9i, and IPE among US adults according to American College of Cardiology/American Heart Association guideline recommendations. Eligibility for PCSK9i and IPE were determined in the following 2 scenarios: (1) assuming existing lipid-lowering therapy as the maximum tolerated before assessing eligibility for novel therapies and (2) assessing eligibility after assuming initiation and maximal escalation of preexisting lipid-lowering therapies and accounting for expected lipid improvements. Of 2729 sampled individuals, representing 149.3 million adults, 1376 had indications for statins, representing 65.8 million or 44.0% (95% CI, 40.9%-47.2%) of adults. Current statin use was 45% of those eligible and was low across demographic groups. A total of 9.7 and 11.6 million adults would benefit from PCSK9i and IPE, respectively, based on lipid profiles and existing therapies. Assuming maximal escalation of statins and addition of ezetimibe, 4.1% (95% CI, 2.8%-5.4%) of adults or 6.1 million would benefit from PCSK9i and 6.8% (95% CI, 5.4%-8.3%) or 10.2 million from IPE.
Conclusions:
Six and 10 million individuals have clinical profiles whereby PCSK9i and IPE, respectively, would be expected to improve cardiovascular outcomes even after maximum escalation of statins and ezetimibe use, but remain undertreated with lipid-lowering therapies. Optimal use of lipid-targeted agents that include these novel agents is needed to improve population health outcomes.




J Am Heart Assoc: 14 Sep 2022:e026075; epub ahead of print
Shen M, Aghajani Nargesi A, Nasir K, Bhatt DL, Khera R
J Am Heart Assoc: 14 Sep 2022:e026075; epub ahead of print | PMID: 36102276
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Impact:
Abstract

Race, Interleukin-6, Genotype, and Cardiovascular Disease in Patients With Chronic Kidney Disease.

Barrows IR, Devalaraja M, Kakkar R, Chen J, ... Amdur RL, CRIC Study Investigators *

Background:
Differences in death rate and cardiovascular disease (CVD) between Black and White patients with chronic kidney disease is attributed to sociocultural factors, comorbidities, genetics, and inflammation. Methods and Results We examined the interaction of race, plasma IL-6 (interleukin-6), and TMPRSS6 genotype as determinants of CVD and mortality in 3031 Chronic Renal Insufficiency Cohort study participants. The primary outcomes were all-cause mortality and a composite of incident myocardial infarction, peripheral artery disease, stroke, and heart failure. During the median follow-up of 10 years, Black patients with chronic kidney disease experienced a significantly higher mortality (34% versus 26%) and CVD composite (41% versus 28%) compared with White patients. After adjustment, TMPRSS6 genotype did not associate with the outcomes. The adjusted hazard ratio for mortality (4.11 [2.48-6.80], P<0.001) and CVD composite (2.52 [1.96-3.24], P<0.001) were higher for the highest versus lowest IL-6 quintile. The adjusted hazards for death per 1-quintile increase in IL-6 in White and Black individuals were 1.53 (1.42-1.64) versus 1.29 (1.20-1.38) (P<0.001), respectively. For CVD composite they were 1.61 (1.50-1.74) versus 1.30 (1.22-1.39) (P<0.001), respectively. In Cox proportional hazard models that included IL-6, there was no longer a racial disparity for death (1.01 [0.87-1.16], P=0.92), but significant unexplained mediation remained for CVD (1.24 [1.07-1.43]; P=0.004). Path models that included IL-6, diabetes, and urine albumin to creatinine ratio were able to identify variables responsible for racial disparity in mortality and CVD.
Conclusions:
Racial differences in mortality and CVD among patients with chronic kidney disease could be explained by good-fitting path models that include selected mediator variables including diabetes and plasma IL-6.




J Am Heart Assoc: 14 Sep 2022:e025627; epub ahead of print
Barrows IR, Devalaraja M, Kakkar R, Chen J, ... Amdur RL, CRIC Study Investigators *
J Am Heart Assoc: 14 Sep 2022:e025627; epub ahead of print | PMID: 36102277
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Impact:
Abstract

Demographic and Regional Trends in Stroke-Related Mortality in Young Adults in the United States, 1999 to 2019.

Ariss RW, Minhas AMK, Lang J, Ramanathan PK, ... Alkhouli M, Nazir S

Background:
Despite improvements in the management and prevention of stroke, increasing hospitalizations for stroke and stagnant mortality rates have been described in young adults. However, there is a paucity of contemporary national mortality estimates in young adults. Methods and Results Trends in mortality related to stroke in young adults (aged 25-64 years) were assessed using the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database. Age-adjusted mortality rates per 100 000 people with associated annual percentage change were calculated. Joinpoint regression was used to assess the trends in the overall sample and different demographic (sex, race and ethnicity, and age) and geographical (state, urban-rural, and regional) subgroups. Between 1999 and 2019, a total of 566 916 stroke-related deaths occurred among young adults. After the initial decline in mortality in the overall population, age-adjusted mortality rate increased from 2013 to 2019 with an associated annual percentage change of 1.5 (95% CI, 1.1-2.0). Mortality rates were higher in men versus women and in non-Hispanic Black people versus individuals of other races and ethnicities. Non-Hispanic American Indian or Alaskan Native people had a marked increase in stroke-related mortality (annual percentage change 2010-2019: 3.3). Furthermore, rural (nonmetropolitan) counties experienced the greatest increase in mortality (annual percentage change 2012-2019: 3.1) compared with urban (metropolitan) counties.
Conclusions:
Following the initial decline in stroke-related mortality, young adults have experienced increasing mortality rates from 2013 to 2019, with considerable differences across demographic groups and regions.




J Am Heart Assoc: 08 Sep 2022:e025903; epub ahead of print
Ariss RW, Minhas AMK, Lang J, Ramanathan PK, ... Alkhouli M, Nazir S
J Am Heart Assoc: 08 Sep 2022:e025903; epub ahead of print | PMID: 36073626
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Impact:
Abstract

Heterogeneity in Cardiovascular Disease Risk Factor Prevalence Among White, African American, African Immigrant, and Afro-Caribbean Adults: Insights From the 2010-2018 National Health Interview Survey.

Baptiste DL, Turkson-Ocran RA, Ogungbe O, Koirala B, ... Dennison Himmelfarb C, Commodore-Mensah Y

Background:
In the United States, Black adults have higher rates of cardiovascular disease (CVD) risk factors than White adults. However, it is unclear how CVD risk factors compare between Black ethnic subgroups, including African Americans (AAs), African immigrants (AIs), and Afro-Caribbeans, and White people. Our objective was to examine trends in CVD risk factors among 3 Black ethnic subgroups and White adults between 2010 and 2018. Methods and Results A comparative analysis of the National Health Interview Survey was conducted among 452 997 participants, examining sociodemographic characteristics and trends in 4 self-reported CVD risk factors (hypertension, diabetes, overweight/obesity, and smoking). Generalized linear models with Poisson distribution were used to obtain predictive probabilities of the CVD risk factors. The sample included 82 635 Black (89% AAs, 5% AIs, and 6% Afro-Caribbeans) and 370 362 White adults. AIs were the youngest, most educated, and least insured group. AIs had the lowest age- and sex-adjusted prevalence of all 4 CVD risk factors. AAs had the highest prevalence of hypertension (2018: 41.9%) compared with the other groups. Overweight/obesity and diabetes prevalence increased in AAs and White adults from 2010 to 2018 (P values for trend <0.001). Smoking prevalence was highest among AAs and White adults, but decreased significantly in these groups between 2010 and 2018 (P values for trend <0.001), as compared with AIs and Afro-Caribbeans.
Conclusions:
We observed significant heterogeneity in CVD risk factors among 3 Black ethnic subgroups compared with White adults. There were disparities (among AAs) and advantages (among AIs and Afro-Caribbeans) in CVD risk factors, suggesting that race alone does not account for disparities in CVD risk factors.




J Am Heart Assoc: 08 Sep 2022:e025235; epub ahead of print
Baptiste DL, Turkson-Ocran RA, Ogungbe O, Koirala B, ... Dennison Himmelfarb C, Commodore-Mensah Y
J Am Heart Assoc: 08 Sep 2022:e025235; epub ahead of print | PMID: 36073627
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Impact:
Abstract

Differential Patterns and Outcomes of 20.6 Million Cardiovascular Emergency Department Encounters for Men and Women in the United States.

Raisi-Estabragh Z, Kobo O, Elbadawi A, Velagapudi P, ... Sun LY, Mamas MA

Background:
We describe sex-differential disease patterns and outcomes of >20.6 million cardiovascular emergency department encounters in the United States. Methods and Results We analyzed primary cardiovascular encounters from the Nationwide Emergency Department Sample between 2016 and 2018. We grouped cardiovascular diagnoses into 15 disease categories. The sample included 48.7% women; median age was 67 (interquartile range, 54-78) years. Men had greater overall baseline comorbidity burden; however, women had higher rates of obesity, hypertension, and cerebrovascular disease. For women, the most common emergency department encounters were essential hypertension (16.0%), hypertensive heart or kidney disease (14.1%), and atrial fibrillation/flutter (10.2%). For men, the most common encounters were hypertensive heart or kidney disease (14.7%), essential hypertension (10.8%), and acute myocardial infarction (10.7%). Women were more likely to present with essential hypertension, hypertensive crisis, atrial fibrillation/flutter, supraventricular tachycardia, pulmonary embolism, or ischemic stroke. Men were more likely to present with acute myocardial infarction or cardiac arrest. In logistic regression models adjusted for baseline covariates, compared with men, women with intracranial hemorrhage had higher risk of hospitalization and death. Women presenting with pulmonary embolism or deep vein thrombosis were less likely to be hospitalized. Women with aortic aneurysm/dissection had higher odds of hospitalization and death. Men were more likely to die following presentations with hypertensive heart or kidney disease, atrial fibrillation/flutter, acute myocardial infarction, or cardiac arrest.
Conclusions:
In this large nationally representative sample of cardiovascular emergency department presentations, we demonstrate significant sex differences in disease distribution, hospitalization, and death.




J Am Heart Assoc: 08 Sep 2022:e026432; epub ahead of print
Raisi-Estabragh Z, Kobo O, Elbadawi A, Velagapudi P, ... Sun LY, Mamas MA
J Am Heart Assoc: 08 Sep 2022:e026432; epub ahead of print | PMID: 36073628
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Impact:
Abstract

Disparities in Geographic Access to Cardiac Rehabilitation in Los Angeles County.

Ebinger JE, Lan R, Driver MP, Rushworth P, ... Bairey Merz CN, Cheng S

Background:
Exercise-based cardiac rehabilitation (CR) is known to reduce morbidity and mortality for patients with cardiac conditions. Sociodemographic disparities in accessing CR persist and could be related to the distance between where patients live and where CR facilities are located. Our objective is to determine the association between sociodemographic characteristics and geographic proximity to CR facilities. Methods and Results We identified actively operating CR facilities across Los Angeles County and used multivariable Poisson regression to examine the association between sociodemographic characteristics of residential proximity to the nearest CR facility. We also calculated the proportion of residents per area lacking geographic proximity to CR facilities across sociodemographic characteristics, from which we calculated prevalence ratios. We found that racial and ethnic minorities, compared with non-Hispanic White individuals, more frequently live ≥5 miles from a CR facility. The greatest geographic disparity was seen for non-Hispanic Black individuals, with a 2.73 (95% CI, 2.66-2.79) prevalence ratio of living at least 5 miles from a CR facility. Notably, the municipal region with the largest proportion of census tracts comprising mostly non-White residents (those identifying as Hispanic or a race other than White), with median annual household income <$60 000, contained no CR facilities despite ranking among the county\'s highest in population density.
Conclusions:
Racial, ethnic, and socioeconomic characteristics are significantly associated with lack of geographic proximity to a CR facility. Interventions targeting geographic as well as nongeographic factors may be needed to reduce disparities in access to exercise-based CR programs. Such interventions could increase the potential of CR to benefit patients at high risk for developing adverse cardiovascular outcomes.




J Am Heart Assoc: 08 Sep 2022:e026472; epub ahead of print
Ebinger JE, Lan R, Driver MP, Rushworth P, ... Bairey Merz CN, Cheng S
J Am Heart Assoc: 08 Sep 2022:e026472; epub ahead of print | PMID: 36073630
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Impact:
Abstract

Blood-Based Fingerprint of Cardiorespiratory Fitness and Long-Term Health Outcomes in Young Adulthood.

Shah RV, Miller P, Colangelo LA, Chernofsky A, ... Lewis GD, Nayor M

Background:
Cardiorespiratory fitness is a powerful predictor of health outcomes that is currently underused in primary prevention, especially in young adults. We sought to develop a blood-based biomarker of cardiorespiratory fitness that is easily translatable across populations. Methods and Results Maximal effort cardiopulmonary exercise testing for quantification of cardiorespiratory fitness (by peak oxygen uptake) and profiling of >200 metabolites at rest were performed in the FHS (Framingham Heart Study; 2016-2019). A metabolomic fitness score was derived/validated in the FHS and was associated with long-term outcomes in the younger CARDIA (Coronary Artery Risk Development in Young Adults) study. In the FHS (derivation, N=451; validation, N=914; age 54±8 years, 53% women, body mass index 27.7±5.3 kg/m2), we used LASSO (least absolute shrinkage and selection operator) regression to develop a multimetabolite score to predict peak oxygen uptake (correlation with peak oxygen uptake r=0.77 in derivation, 0.61 in validation; both P<0.0001). In a linear model including clinical risk factors, a ≈1-SD higher metabolomic fitness score had equivalent magnitude of association with peak oxygen uptake as a 9.2-year age increment. In the CARDIA study (N=2300, median follow-up 26.9 years, age 32±4 years, 44% women, 44% Black individuals), a 1-SD higher metabolomic fitness score was associated with a 44% lower risk for mortality (hazard ratio [HR], 0.56 [95% CI, 0.47-0.68]; P<0.0001) and 32% lower risk for cardiovascular disease (HR, 0.68 [95% CI, 0.55-0.84]; P=0.0003) in models adjusted for age, sex, and race, which remained robust with adjustment for clinical risk factors.
Conclusions:
A blood-based biomarker of cardiorespiratory fitness largely independent of traditional risk factors is associated with long-term risk of cardiovascular disease and mortality in young adults.




J Am Heart Assoc: 08 Sep 2022:e026670; epub ahead of print
Shah RV, Miller P, Colangelo LA, Chernofsky A, ... Lewis GD, Nayor M
J Am Heart Assoc: 08 Sep 2022:e026670; epub ahead of print | PMID: 36073631
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Impact:
Abstract

Racial Disparity in Referral for Catheter Ablation for Atrial Fibrillation at a Single Integrated Health System.

Duke JM, Muhammad LN, Song J, Tanaka Y, ... Khan SS, Passman RS

Background:
Guidelines recommend catheter ablation of atrial fibrillation (AFCA) as an option for rhythm control. Studies have shown that Black patients are less likely to undergo AFCA compared with White patients. We investigated whether differences in referral patterns play a role in this observed disparity. Methods and Results Using an integrated repository from the electronic medical record at Northwestern Medicine, we conducted a retrospective cohort study of outpatients with newly diagnosed atrial fibrillation. Baseline characteristics by race and ethnicity were compared. Logistic regression models adjusted for socioeconomic and health factors were constructed to determine the association between race and ethnicity and binary dependent variables including referrals and visits to general cardiology and cardiac electrophysiology (EP) and AFCA. Of 5445 patients analyzed, 4652 were non-Hispanic White (NHW) and 793 were non-Hispanic Black (NHB). In adjusted models, NHB patients initially diagnosed with atrial fibrillation in internal medicine and primary care had a significantly greater odds of referral to general cardiology; among all patients in the cohort, there was no significant difference in the odds of referral to EP between NHB and NHW patients; and there were no differences in the odds of completing a visit in general cardiology or EP. Among patients completing an EP visit, NHB patients were less likely to undergo AFCA (odds ratio, 0.63 [95% CI, 0.40-0.98], P=0.040).
Conclusions:
Similar referral rates to general cardiology and EP were observed between NHB and NHW patients. Despite this, NHB patients were less likely to undergo AFCA.




J Am Heart Assoc: 08 Sep 2022:e025831; epub ahead of print
Duke JM, Muhammad LN, Song J, Tanaka Y, ... Khan SS, Passman RS
J Am Heart Assoc: 08 Sep 2022:e025831; epub ahead of print | PMID: 36073632
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Impact:
Abstract

Effects of Nicorandil Administration on Infarct Size in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: The CHANGE Trial.

Qian G, Zhang Y, Dong W, Jiang ZC, ... Li YJ, Chen YD

Background:
Nicorandil was reported to improve microvascular dysfunction and reduce reperfusion injury when administered before primary percutaneous coronary intervention. In this multicenter, prospective, randomized, double-blind clinical trial (CHANGE [Effects of Nicorandil Administration on Infarct Size in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention]), we investigated the effects of nicorandil administration on infarct size in patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods and Results A total of 238 patients with ST-segment-elevation myocardial infarction were randomized to receive intravenous nicorandil (n=120) or placebo (n=118) before reperfusion. Patients in the nicorandil group received a 6-mg intravenous bolus of nicorandil followed by continuous infusion at a rate of 6 mg/h. Patients in the placebo group received the same dose of placebo. The predefined primary end point was infarct size on cardiac magnetic resonance (CMR) imaging performed at 5 to 7 days and 6 months after reperfusion. CMR imaging was performed in 201 patients (84%). Infarct size on CMR imaging at 5 to 7 days after reperfusion was significantly smaller in the nicorandil group compared with the placebo (control) group (26.5±17.1 g versus 32.4±19.3 g; P=0.022), and the effect remained significant on long-term CMR imaging at 6 months after reperfusion (19.5±14.4 g versus 25.7±15.4 g; P=0.008). The incidence of no-reflow/slow-flow phenomenon during primary percutaneous coronary intervention was much lower in the nicorandil group (9.2% [11/120] versus 26.3% [31/118]; P=0.001), and thus, complete ST-segment resolution was more frequently observed in the nicorandil group (90.8% [109/120] versus 78.0% [92/118]; P=0.006). Left ventricular ejection fraction on CMR imaging was significantly higher in the nicorandil group than in the placebo group at both 5 to 7 days (47.0±10.2% versus 43.3±10.0%; P=0.011) and 6 months (50.1±9.7% versus 46.4±8.5%; P=0.009) after reperfusion.
Conclusions:
In the present trial, administration of nicorandil before primary percutaneous coronary intervention led to improved myocardial perfusion grade, increased left ventricular ejection fraction, and reduced myocardial infarct size in patients with ST-segment-elevation myocardial infarction. Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03445728.




J Am Heart Assoc: 08 Sep 2022:e026232; epub ahead of print
Qian G, Zhang Y, Dong W, Jiang ZC, ... Li YJ, Chen YD
J Am Heart Assoc: 08 Sep 2022:e026232; epub ahead of print | PMID: 36073634
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Impact:
Abstract

Risk of Postdischarge Bleeding From Dual Antiplatelet Therapy After Percutaneous Coronary Intervention Among US Black and White Adults.

Heindl B, Clarkson S, Parcha V, Dillon C, ... Beasley M, Limdi N

Background:
Dual antiplatelet therapy after percutaneous coronary intervention reduces myocardial infarctions but increases bleeding. The risk of bleeding may be higher among Black patients for unknown reasons. Bleeding risk scores have not been validated among Black patients. We assessed the difference in bleeding risk between Black and White patients along with the performance of the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Anti Platelet Therapy, Patterns of Nonadherence to Antiplatelet Regimens in Stented Patients, and Academic Research Consortium for High Bleeding Risk scores among both groups. Methods and Results This was a single-center prospective study of patients who underwent percutaneous coronary intervention (2014-2019) and were followed for 1 year. The outcome was postdischarge Bleeding Academic Research Consortium 2 to 5 bleeding. Incidence rates were reported. Cox proportional hazards models measured the effect of self-reported Black race on bleeding and determined the predictors of bleeding among 19 a priori variables. The 3 risk scores were assessed among Black and White patients separately using the Harrell concordance index. Of 1529 included patients, 342 (22.4%) self-reported as being Black race. Unadjusted bleeding rates were 22.7 per 100 person-years among Black patients versus 16.3 among White patients (hazard ratio, 1.41 [95% CI, 1.00-2.00], P=0.052). Predictors of bleeding were age, glomerular filtration rate <30 mL/min per 1.73 m2, prior bleeding, ticagrelor or prasugrel use, and anticoagulant use. Among Black and White patients, respectively, the C-indexes were the following: 0.644 versus 0.600 for Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Anti Platelet Therapy (P<0.001 for both), 0.620 versus 0.612 for Patterns of Nonadherence to Antiplatelet Regimens in Stented Patients (P=0.003 and P<0.001, respectively), and 0.600 versus 0.598 for Academic Research Consortium for High Bleeding Risk (P=0.006 and P<0.001, respectively).
Conclusions:
The risk of dual antiplatelet therapy-associated postdischarge Bleeding Academic Research Consortium 2 to 5 bleeding was not significantly different between self-reported Black and White patients. Bleeding risk scores performed similarly among both groups.




J Am Heart Assoc: 08 Sep 2022:e024412; epub ahead of print
Heindl B, Clarkson S, Parcha V, Dillon C, ... Beasley M, Limdi N
J Am Heart Assoc: 08 Sep 2022:e024412; epub ahead of print | PMID: 36073636
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Impact:
Abstract

Evaluation of an Ambulatory ECG Analysis Platform Using Deep Neural Networks in Routine Clinical Practice.

Fiorina L, Maupain C, Gardella C, Manenti V, ... Bourmaud A, Marijon E

Background:
Holter analysis requires significant clinical resources to achieve a high-quality diagnosis. This study sought to assess whether an artificial intelligence (AI)-based Holter analysis platform using deep neural networks is noninferior to a conventional one used in clinical routine in detecting a major rhythm abnormality. Methods and Results A total of 1000 Holter (24-hour) recordings were collected from 3 tertiary hospitals. Recordings were independently analyzed by cardiologists for the AI-based platform and by electrophysiologists as part of clinical practice for the conventional platform. For each Holter, diagnostic performance was evaluated and compared through the analysis of the presence or absence of 5 predefined cardiac abnormalities: pauses, ventricular tachycardia, atrial fibrillation/flutter/tachycardia, high-grade atrioventricular block, and high burden of premature ventricular complex (>10%). Analysis duration was monitored. The deep neural network-based platform was noninferior to the conventional one in its ability to detect a major rhythm abnormality. There were no statistically significant differences between AI-based and classical platforms regarding the sensitivity and specificity to detect the predefined abnormalities except for atrial fibrillation and ventricular tachycardia (atrial fibrillation, 0.98 versus 0.91 and 0.98 versus 1.00; pause, 0.95 versus 1.00 and 1.00 versus 1. 00; premature ventricular contractions, 0.96 versus 0.87 and 1.00 versus 1.00; ventricular tachycardia, 0.97 versus 0.68 and 0.99 versus 1.00; atrioventricular block, 0.93 versus 0.57 and 0.99 versus 1.00). The AI-based analysis was >25% faster than the conventional one (4.4 versus 6.0 minutes; P<0.001).
Conclusions:
These preliminary findings suggest that an AI-based strategy for the analysis of Holter recordings is faster and at least as accurate as a conventional analysis by electrophysiologists.




J Am Heart Assoc: 08 Sep 2022:e026196; epub ahead of print
Fiorina L, Maupain C, Gardella C, Manenti V, ... Bourmaud A, Marijon E
J Am Heart Assoc: 08 Sep 2022:e026196; epub ahead of print | PMID: 36073638
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Impact:
Abstract

Coronary Artery Restenosis in Women by History of Preeclampsia.

Lin A, Pehrson M, Sarno G, Fraser A, ... Pihlsgård M, Timpka S

Background:
A history of preeclampsia is associated with increased risk of coronary artery disease and experimental evidence suggests that a history of preeclampsia also increases the risk of restenosis. However, the extent to which a history of preeclampsia is associated with risk of restenosis after percutaneous coronary intervention in women is unknown. Methods and Results We included 6065 parous women aged ≤65 years with first percutaneous coronary intervention on 9452 segments 2006 to 2017, linking nationwide data on percutaneous coronary intervention and delivery history in Sweden. Main outcomes were clinical restenosis and target lesion revascularization within 2 years. We accounted for segment-, procedure-, and patient-related potential predictors of restenosis in proportional hazards regression models. Restenosis occurred in 345 segments (3.7%) and target lesion revascularization was performed on 383 patients (6.3%). A history of preeclampsia was neither significantly associated with risk of restenosis (predictor-accounted hazard ratio [HR], 0.71 [95% CI, 0.41-1.23]) nor target lesion revascularization (0.74 [95% CI, 0.51-1.07]) compared with a normotensive pregnancy history. When term and preterm preeclampsia were investigated separately, segments in women with a history of term preeclampsia had a lower risk of restenosis (predictor-accounted HR, 0.45 [95% CI, 0.21-0.94]). A history of preeclampsia was not significantly associated with death by any cause within 2 years of the index procedure (predictor-accounted HR 1.06, [95% CI, 0.62-1.80]).
Conclusions:
A history of preeclampsia was not associated with increased risk of restenosis but instead some evidence pointed to a decreased risk. To facilitate future studies and allow for replication, concomitant collection of data on pregnancy complication history and percutaneous coronary intervention outcomes in women is warranted.




J Am Heart Assoc: 08 Sep 2022:e026287; epub ahead of print
Lin A, Pehrson M, Sarno G, Fraser A, ... Pihlsgård M, Timpka S
J Am Heart Assoc: 08 Sep 2022:e026287; epub ahead of print | PMID: 36073639
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Impact:
Abstract

ANGPTL3 and Cardiovascular Outcomes in Patients With Acute Coronary Syndrome and Obstructive Sleep Apnea.

Lv Q, Jiao X, Yu H, Sun Q, ... Nie S, Qin Y

Background:
The aim of this prospective study was to determine the impact of elevated ANGPTL3 (angiopoietin-like protein 3) on cardiovascular events (CVEs) following acute coronary syndrome (ACS) in patients with or without obstructive sleep apnea (OSA). Methods and Results A total of 1174 patients with ACS underwent successful percutaneous coronary intervention were included in this prospective cohort study (NCT03362385). Patients were categorized according to the apnea-hypopnea index (≥15 events/h, OSA) and further classified by ANGPTL3 levels. We analyzed the incidence of CVEs in patients with ACS according to the status of OSA and ANGPTL3. During a median of 3.1 years of follow-up, 217 (18.48%) CVEs occurred. The patients with ACS with OSA had higher ANGPTL3 levels than those without OSA (30.4 [20.9-43.2] versus 27.80 [19.1-41.5] ng/mL; P<0.001). In all patients with ACS, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with an increased risk of CVEs with hazard ratios (HRs) of 1.555 (95% CI, 1.010-2.498) and 2.489 (95% CI 1.613-3.840), respectively. When the status of OSA or not was incorporated in stratifying factors, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with a significantly higher risk of CVEs in patients with ACS with OSA (HR, 1.916 [95% CI, 1.019-3.601] and HR, 2.692 [95% CI, 1.379-4.503]) but not without OSA. Moreover, adding ANGPTL3 to the Cox model increased C-statistic values by 0.035 and 0.029 in the OSA group and all patients with ACS, respectively, but was not statistically improved in patients with ACS without OSA.
Conclusions:
In conclusion, our study demonstrates a predictive impact of plasma ANGPTL3 on cardiovascular risk in patients with ACS, especially in patients with ACS with OSA. It might be of clinical value in refining risk stratification and tailoring treatment of patients with ACS and OSA. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03362385.




J Am Heart Assoc: 08 Sep 2022:e025955; epub ahead of print
Lv Q, Jiao X, Yu H, Sun Q, ... Nie S, Qin Y
J Am Heart Assoc: 08 Sep 2022:e025955; epub ahead of print | PMID: 36073641
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Impact:
Abstract

Housekeeping Proteins Exhibit a High Level of Expression Variability Within Control Group and Between Ischemic Human Heart Biopsies.

Colombe AS, Gerbaud P, Benitah JP, Pidoux G

Background:
Human cardiac biopsies are widely used in clinical and fundamental research to decipher molecular events that characterize cardiac physiological and pathophysiological states. One of the main approaches relies on the analysis of semiquantitative immunoblots that reveals alterations in protein expression levels occurring in diseased hearts. To maintain semiquantitative results, expression level of target proteins must be standardized. The expression of HKP (housekeeping proteins) is commonly used to this purpose. Methods and Results We evaluated the stability of HKP expression (actin, β-tubulin, GAPDH, vinculin, and calsequestrin) and total protein staining within control (coefficient of variation) and comparatively with ischemic human heart biopsies (P value). All HKP exhibited a high level of intragroup (ie, actin, β-tubulin, and GAPDH) and/or intergroup variability (ie, GAPDH, vinculin, and calsequestrin). Among all, we found total protein staining to exhibit the highest degree of stability within and between groups, which makes this reference the best to study protein expression level in human biopsies from ischemic hearts and age-matched controls. In addition, we illustrated that using an inappropriate reference protein marker misleads interpretation on SERCA2 (sarco/endoplasmic reticulum Ca2+ ATPase) and cMyBPC (cardiac myosin binding protein-C) expression level after myocardial infarction.
Conclusions:
These reemphasize the need to standardize the level of protein expression with total protein staining in comparative immunoblot studies on human samples from control and diseased hearts.




J Am Heart Assoc: 08 Sep 2022:e026292; epub ahead of print
Colombe AS, Gerbaud P, Benitah JP, Pidoux G
J Am Heart Assoc: 08 Sep 2022:e026292; epub ahead of print | PMID: 36073642
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Abstract

Fluid Volume Homeostasis in Heart Failure: A Tale of 2 Circulations.

Miller WL
Fluid volume homeostasis in health and heart failure (HF) requires a complex interaction of 2 systems, the intravascular and interstitial-lymphatic circulations. With the development of HF both the intravascular and interstitial compartments undergo variable degrees of volume remodeling which can include significant expansion. This reflects the impact of multiple pathophysiologic mechanisms on both fluid compartments which initially play a compensatory role to stabilize intravascular circulatory integrity but with progression in HF can evolve to produce the various manifestations of volume overload and clinical HF congestion. The intent of this review is to help enhance recognition of the pathophysiologic and clinical importance of the interlinked roles of these 2 circulatory systems in volume regulation and chronic HF. It would also be hoped that a better understanding of the interacting functions of the intravascular and interstitial-lymphatic fluid compartments can potentially aid development of novel management strategies particularly addressing the generally undertargeted interstitial-lymphatic system and help bring such approaches forward through a more integrated view of these 2 circulatory systems.



J Am Heart Assoc: 08 Sep 2022:e026668; epub ahead of print
Miller WL
J Am Heart Assoc: 08 Sep 2022:e026668; epub ahead of print | PMID: 36073644
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Impact:
Abstract

Left Atrial Volumes and Function, and Long-Term Incidence of Ischemic Stroke in the General Population.

Larsen BS, Olsen FJ, Andersen DM, Madsen CV, ... Sajadieh A, Biering-Sørensen T

Background:
Left atrial (LA) volumes and emptying fraction in the general population may address structural and functional aspects of atrial cardiomyopathy associated with long-term risk of ischemic stroke in the absence of atrial fibrillation or prior stroke. We investigated the association between LA volumes and function and ischemic stroke. Methods and Results In a community-based cohort, we measured LA minimal volume, LA maximal volume, and LA emptying fraction by transthoracic echocardiography. The primary end point was ischemic stroke. Participants with known atrial fibrillation or prior ischemic stroke were excluded, which resulted in 1866 participants. The mean age was 58±16 years, and 57% were women. During a median follow-up of 16.5 years (interquartile range: 11.4-16.8 years), 176 (9.4%) ischemic strokes occurred. In multivariable cause-specific regression models and competing risk models with death as a competing risk, LA emptying fraction was associated with ischemic stroke (hazard ratio [HR], 1.14 per 10% decrease [95% CI, 1.02-1.28]) and (subdistribution HR, 1.14 [95% CI, 1.01-1.29]). This association remained when adjusting for participants who developed atrial fibrillation during follow-up (HR, 1.12 per 10% decrease [95% CI, 1.00-1.26]). Indexed LA volumes were not associated with ischemic stroke in the same models. LA emptying fraction and indexed LA volumes were not associated with all-cause mortality.
Conclusions:
Lower LA emptying fraction measured by transthoracic echocardiography was associated with future ischemic stroke independently of incident atrial fibrillation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02993172.




J Am Heart Assoc: 08 Sep 2022:e027031; epub ahead of print
Larsen BS, Olsen FJ, Andersen DM, Madsen CV, ... Sajadieh A, Biering-Sørensen T
J Am Heart Assoc: 08 Sep 2022:e027031; epub ahead of print | PMID: 36073645
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Impact:
Abstract

Clinical Outcomes of Rhythm Control Strategies for Asymptomatic Atrial Fibrillation According to the Quality-of-Life Score: The CODE-AF (Comparison Study of Drugs for Symptom Control and Complication Prevention of Atrial Fibrillation) Registry.

Kim JY, Park HS, Park HW, Choi EK, ... Joung B, Park KM

Background:
Atrial fibrillation (AF) is associated with an increased risk of poor cardiovascular outcomes; appropriate rhythm control can reduce the incidence of these adverse events. Therefore, catheter ablation is recommended in symptomatic patients with AF. The aims of this study were to compare AF-related outcomes according to a baseline symptom scale score and to determine the best treatment strategy for asymptomatic patients with AF. Methods and Results This study enrolled all patients who completed a baseline Atrial Fibrillation Effect on Quality-of-Life (AFEQT) survey in a prospective observational registry. The patients were divided into 2 groups according to AFEQT score at baseline; scores ≤80 were defined as symptomatic, whereas scores >80 represented asymptomatic patients. The primary outcome was defined as a composite of hospitalization for heart failure, ischemic stroke, or cardiac death. This study included 1515 patients (mean age: 65.7±10.5 years; 998 [65.9%] men). The survival curve showed a poorer outcome in the symptomatic group compared with the asymptomatic group (log-rank P=0.04). Rhythm control led to a significantly lower risk of a composite outcome in asymptomatic patients (hazard ratio [HR], 0.47 [95% CI, 0.27-0.84], P=0.01). Rhythm control was associated with more favorable composite outcomes in the asymptomatic group with paroxysmal AF, left atrium diameter ≤50 mm, and CHA2DS2-VASc score ≥3.
Conclusions:
Symptomatic patients with AF experienced more adverse outcomes compared with asymptomatic patients. In asymptomatic patients with AF, a strategy of rhythm control improved the outcomes, especially with paroxysmal AF, smaller left atrium size, or higher stroke risk. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02786095.




J Am Heart Assoc: 08 Sep 2022:e025956; epub ahead of print
Kim JY, Park HS, Park HW, Choi EK, ... Joung B, Park KM
J Am Heart Assoc: 08 Sep 2022:e025956; epub ahead of print | PMID: 36073646
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Abstract

Heart Failure Strategically Focused Research Network: Summary of Results and Future Directions.

Felker GM, Buttrick P, Rosenzweig A, Abel ED, ... Stehlik J, Selzman CH
Heart failure remains among the most common and morbid health conditions. The Heart Failure Strategically Focused Research Network (HF SFRN) was funded by the American Heart Association to facilitate collaborative, high-impact research in the field of heart failure across the domains of basic, clinical, and population research. The Network was also charged with developing training opportunities for young investigators. Four centers were funded in 2016: Duke University, University of Colorado, University of Utah, and Massachusetts General Hospital-University of Massachusetts. This report summarizes the aims of each center and major research accomplishments, as well as training outcomes from the HF SFRN.



J Am Heart Assoc: 08 Sep 2022:e025517; epub ahead of print
Felker GM, Buttrick P, Rosenzweig A, Abel ED, ... Stehlik J, Selzman CH
J Am Heart Assoc: 08 Sep 2022:e025517; epub ahead of print | PMID: 36073647
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Impact:
Abstract

Nonadherence by Serum Drug Analyses in Resistant Hypertension: 7-Year Follow-Up of Patients Considered Adherent by Directly Observed Therapy.

Halvorsen LV, Bergland OU, Søraas CL, Larstorp ACK, ... Opdal MS, Høieggen A

Background:
Measurement of serum concentrations of drugs is a novelty found useful in detecting poor drug adherence in patients taking ≥2 antihypertensive agents. Regarding patients with treatment-resistant hypertension, we previously based our assessment on directly observed therapy. The present study aimed to investigate whether serum drug measurements in patients with resistant hypertension offer additional information regarding drug adherence, beyond that of initial assessment with directly observed therapy. Methods and Results Nineteen patients assumed to have true treatment-resistant hypertension and adherence to antihypertensive drugs based on directly observed therapy were investigated repeatedly through 7 years. Serum concentrations of antihypertensive drugs were measured by ultra-high-performance liquid chromatography-tandem mass spectrometry from blood samples taken at baseline, 6-month, 3-year, and 7-year visits. Cytochrome P450 polymorphisms, self-reported adherence and beliefs about medicine were performed as supplement investigations. Seven patients (37%) were redefined as nonadherent based on their serum concentrations during follow-up. All patients reported high adherence to medications. Nonadherent patients expressed lower necessity and higher concerns regarding intake of antihypertensive medication (P=0.003). Cytochrome P450 polymorphisms affecting metabolism of antihypertensive drugs were found in 16 patients (84%), 21% were poor metabolizers, and none were ultra-rapid metabolizers. Six of 7 patients redefined as nonadherent had cytochrome P450 polymorphisms, however, not explaining the low serum drug concentrations measured in these patients.
Conclusions:
Our data suggest that repeated measurements of serum concentrations of antihypertensive drugs revealed nonadherence in one-third of patients previously evaluated as adherent and treatment resistant by directly observed therapy, thereby improving the accuracy of adherence evaluation. Registration URL: https://www.clinicaltrials.gov; unique identifier: NCT01673516.




J Am Heart Assoc: 08 Sep 2022:e025879; epub ahead of print
Halvorsen LV, Bergland OU, Søraas CL, Larstorp ACK, ... Opdal MS, Høieggen A
J Am Heart Assoc: 08 Sep 2022:e025879; epub ahead of print | PMID: 36073648
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Impact:
Abstract

Eligibility for Posthospitalization Venous Thromboembolism Prophylaxis in Hospitalized Patients With COVID-19: A Retrospective Cohort Study.

Vaughn VM, Ratz D, McLaughlin ES, Horowitz JK, ... Kaatz S, Barnes GD

Background:
A recent randomized trial, the MICHELLE trial, demonstrated improved posthospital outcomes with a 35-day course of prophylactic rivaroxaban for patients hospitalized with COVID-19 at high risk of venous thromboembolism. We explored how often these findings may apply to an unselected clinical population of patients hospitalized with COVID-19. Methods and Results Using a 35-hospital retrospective cohort of patients hospitalized between March 7, 2020, and January 23, 2021, with COVID-19 (MI-COVID19 database), we quantified the percentage of hospitalized patients with COVID-19 who would be eligible for rivaroxaban at discharge per MICHELLE trial criteria and report clinical event rates. The main clinical outcome was derived from the MICHELLE trial and included a composite of symptomatic venous thromboembolism, pulmonary embolus-related death, nonhemorrhagic stroke, and cardiovascular death at 35 days. Multiple sensitivity analyses tested different eligibility and exclusion criteria definitions to determine the effect on eligibility for postdischarge anticoagulation prophylaxis. Of 2016 patients hospitalized with COVID-19 who survived to discharge and did not have another indication for anticoagulation, 25.9% (n=523) would be eligible for postdischarge thromboprophylaxis per the MICHELLE trial criteria (range, 2.9%-39.4% on sensitivity analysis). Of the 416 who had discharge anticoagulant data collected, only 13.2% (55/416) were actually prescribed a new anticoagulant at discharge. Of patients eligible for rivaroxaban per the MICHELLE trial, the composite clinical outcome occurred in 1.2% (6/519); similar outcome rates were 5.7% and 0.63% in the MICHELLE trial\'s control (no anticoagulation) and intervention (rivaroxaban) groups, respectively. Symptomatic venous thromboembolism events and all-cause mortality were 6.2% (32/519) and 5.66% in the MI-COVID19 and MICHELLE trial control cohorts, respectively.
Conclusions:
Across 35 hospitals in Michigan, ≈1 in 4 patients hospitalized with COVID-19 would qualify for posthospital thromboprophylaxis. With only 13% of patients actually receiving postdischarge prophylaxis, there is a potential opportunity for improvement in care.




J Am Heart Assoc: 08 Sep 2022:e025914; epub ahead of print
Vaughn VM, Ratz D, McLaughlin ES, Horowitz JK, ... Kaatz S, Barnes GD
J Am Heart Assoc: 08 Sep 2022:e025914; epub ahead of print | PMID: 36073649
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Impact:
Abstract

Impact of Socioeconomic Status and Residence Distance on Infant Heart Disease Outcomes in Canada.

Olugbuyi O, Smith C, Kaul P, Dover DC, ... Eckersley L, Hornberger LK

Background:
Socioeconomic status (SES) impacts clinical outcomes associated with severe congenital heart disease (sCHD). We examined the impact of SES and remoteness of residence (RoR) on congenital heart disease (CHD) outcomes in Canada, a jurisdiction with universal health insurance. Methods and Results All infants born in Canada (excluding Quebec) from 2008 to 2018 and hospitalized with CHD requiring intervention in the first year were identified. Neighborhood level SES income quintiles were calculated, and RoR was categorized as residing <100 km, 100 to 299 km, or >300 km from the closest of 7 cardiac surgical programs. In-hospital mortality at <1 year was the primary outcome, adjusted for preterm birth, low birth weight, and extracardiac pathology. Among 7711 infants, 4485 (58.2%) had moderate CHD (mCHD) and 3226 (41.8%) had sCHD. Overall mortality rate was 10.5%, with higher rates in sCHD than mCHD (13.3% versus 8.5%, respectively). More CHD infants were in the lowest compared with the highest SES category (27.1% versus 15.0%, respectively). The distribution of CHD across RoR categories was 52.3%, 21.3%, and 26.4% for <100 km, 100 to 299 km, and >300 km, respectively. Although SES and RoR had no impact on sCHD mortality, infants with mCHD living >300 km had a higher risk of mortality relative to those living <100 km (adjusted odds ratio [aOR], 1.43 [95% CI, 1.11-1.84]). Infants with mCHD within the lowest SES quintile and living farthest away had the highest risk for mortality (aOR, 1.74 [95% CI, 1.08-2.81]).
Conclusions:
In Canada, neither RoR nor SES had an impact on outcomes of infants with sCHD. Greater RoR, however, may contribute to higher risk of mortality among infants with mCHD.




J Am Heart Assoc: 08 Sep 2022:e026627; epub ahead of print
Olugbuyi O, Smith C, Kaul P, Dover DC, ... Eckersley L, Hornberger LK
J Am Heart Assoc: 08 Sep 2022:e026627; epub ahead of print | PMID: 36073651
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Impact:
Abstract

Body Mass Index Trajectory and Outcome Post Fontan Procedure.

Payne E, Garden F, d\'Udekem Y, McCallum Z, ... Wilson TG, Ayer J

Background:
Patients with a single ventricle who experience early life growth failure suffer high morbidity and mortality in the perisurgical period. However, long-term implications of poor infant growth, as well as associations between body mass index (BMI) and outcome in adulthood, remain unclear. We aimed to model BMI trajectories of patients with a single ventricle undergoing a Fontan procedure to determine trajectory-based differences in baseline characteristics and long-term clinical outcomes. Methods and Results We performed a retrospective analysis of medical records from patients in the Australia and New Zealand Fontan Registry receiving treatment at the Royal Children\'s Hospital, The Children\'s Hospital at Westmead, Royal Melbourne Hospital, and Royal Prince Alfred Hospital from 1981 to 2018. BMI trajectories were modeled in 496 patients using latent class growth analysis from 0 to 6 months, 6 to 60 months, and 5 to 16 years. Trajectories were compared regarding long-term incidence of severe Fontan failure (defined as mortality, heart transplantation, Fontan takedown, or New York Heart Association class III/IV heart failure). Three trajectories were found for male and female subjects at each age group-lower, middle, higher. Subjects in the lower trajectory at 0 to 6 months were more likely to have an atriopulmonary Fontan and experienced increased mortality long term. No association was found between higher BMI trajectory, current BMI, and long-term outcome.
Conclusions:
Poor growth in early life correlates with increased long-term severe Fontan failure. Delineation of distinct BMI trajectories can be used in larger and older cohorts to find optimal BMI targets for patient outcome.




J Am Heart Assoc: 08 Sep 2022:e025931; epub ahead of print
Payne E, Garden F, d'Udekem Y, McCallum Z, ... Wilson TG, Ayer J
J Am Heart Assoc: 08 Sep 2022:e025931; epub ahead of print | PMID: 36073652
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Impact:
Abstract

Sex-Based Differences in 30-Day Readmissions After Cardiac Arrest: Analysis of the Nationwide Readmissions Database.

Sobti NK, Yeo I, Cheung JW, Feldman DN, ... Wong SC, Kim LK

Background:
There are limited data on the sex-based differences in the outcome of readmission after cardiac arrest. Methods and Results Using the Nationwide Readmissions Database, we analyzed patients hospitalized with cardiac arrest between 2010 and 2015. Based on International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, we identified comorbidities, therapeutic interventions, and outcomes. Multivariable logistic regression was performed to assess the independent association between sex and outcomes. Of 835 894 patients, 44.4% (n=371 455) were women, of whom 80.7% presented with pulseless electrical activity (PEA)/asystole. Women primarily presented with PEA/asystole (80.7% versus 72.4%) and had a greater comorbidity burden than men, as assessed using the Elixhauser Comorbidity Score. Thirty-day readmission rates were higher in women than men in both PEA/asystole (20.8% versus 19.6%) and ventricular tachycardia/ventricular fibrillation arrests (19.4% versus 17.1%). Among ventricular tachycardia/ventricular fibrillation arrest survivors, women were more likely than men to be readmitted because of noncardiac causes, predominantly infectious, respiratory, and gastrointestinal illnesses. Among PEA/asystole survivors, women were at higher risk for all-cause (adjusted odds ratio [aOR], 1.07; [95% CI, 1.03-1.11]), cardiac-cause (aOR, 1.15; [95% CI, 1.06-1.25]), and noncardiac-cause (aOR, 1.13; [95% CI, 1.04-1.22]) readmission. During the index hospitalization, women were less likely than men to receive therapeutic procedures, including coronary angiography and targeted therapeutic management. While the crude case fatality rate was higher in women, in both ventricular tachycardia/ventricular fibrillation (51.8% versus 47.4%) and PEA/asystole (69.3% versus 68.5%) arrests, sex was not independently associated with increased crude case fatality after adjusting for differences in baseline characteristics.
Conclusions:
Women are at increased risk of readmission following cardiac arrest, independent of comorbidities and therapeutic interventions.




J Am Heart Assoc: 08 Sep 2022:e025779; epub ahead of print
Sobti NK, Yeo I, Cheung JW, Feldman DN, ... Wong SC, Kim LK
J Am Heart Assoc: 08 Sep 2022:e025779; epub ahead of print | PMID: 36073654
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Impact:
Abstract

Network Meta-Analysis of Randomized Trials Evaluating the Comparative Efficacy of Lipid-Lowering Therapies Added to Maximally Tolerated Statins for the Reduction of Low-Density Lipoprotein Cholesterol.

Toth PP, Bray S, Villa G, Palagashvili T, ... Stroes ESG, Worth GM

Background:
Lowering low-density lipoprotein cholesterol (LDL-C) levels decreases major cardiovascular events and is recommended for patients at elevated cardiovascular risk. However, appropriate doses of statin therapy are often insufficient to reduce LDL-C in accordance with current guidelines. In such cases, treatment could be supplemented with nonstatin lipid-lowering therapy. Methods and Results A systematic literature review and network meta-analysis were conducted on randomized controlled trials of nonstatin lipid-lowering therapy added to maximally tolerated statins, including statin-intolerant patients. The primary objective was to assess relative efficacy of nonstatin lipid-lowering therapy in reducing LDL-C levels at week 12. Secondary objectives included the following: LDL-C level reduction at week 24 and change in non-high-density lipoprotein cholesterol and apolipoprotein B at week 12. There were 48 randomized controlled trials included in the primary network meta-analysis. All nonstatin agents significantly reduced LDL-C from baseline versus placebo, regardless of background therapy. At week 12, evolocumab, 140 mg every 2 weeks (Q2W)/420 mg once a month, and alirocumab, 150 mg Q2W, were the most efficacious regimens, followed by alirocumab, 75 mg Q2W, alirocumab, 300 mg once a month, inclisiran, bempedoic acid/ezetimibe fixed-dose combination, and ezetimibe and bempedoic acid used as monotherapies. Primary end point results were generally consistent at week 24, and for other lipid end points at week 12.
Conclusions:
Evolocumab, 140 mg Q2W/420 mg once a month, and alirocumab, 150 mg Q2W, were consistently the most efficacious nonstatin regimens when added to maximally tolerated statins to lower LDL-C, non-high-density lipoprotein cholesterol, and apolipoprotein B levels and facilitate attainment of guideline-recommended risk-stratified lipoprotein levels.




J Am Heart Assoc: 08 Sep 2022:e025551; epub ahead of print
Toth PP, Bray S, Villa G, Palagashvili T, ... Stroes ESG, Worth GM
J Am Heart Assoc: 08 Sep 2022:e025551; epub ahead of print | PMID: 36073669
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Impact:
Abstract

Clinical Characteristics of Patients Undergoing Right Heart Catheterizations in Community Hospitals.

Jansen SMA, Huis In \'t Veld AE, Tolen PHCG, Jacobs W, ... de Man FS, Bogaard HJ

Background:
Recognition of precapillary pulmonary hypertension (PH) has significant implications for patient management. However, the low a priori chance to find this rare condition in community hospitals may create a barrier against performing a right heart catheterization (RHC). This could result in misclassification of PH and delayed diagnosis/treatment of precapillary PH. Therefore, we investigated patient characteristics and echocardiographic parameters associated with the decision whether to perform an RHC in patients with incident PH in 12 Dutch community hospitals. Methods and Results In total, 275 patients were included from the OPTICS (Optimizing PH Diagnostic Network in Community Hospitals) registry, a prospective cohort study with patients with incident PH; 157 patients were diagnosed with RHC (34 chronic thromboembolic PH, 38 pulmonary arterial hypertension, 81 postcapillary PH, 4 miscellaneous PH), while 118 patients were labeled as probable postcapillary PH without hemodynamic confirmation. Multivariable analysis showed that older age (>60 years), left ventricular diastolic dysfunction grade 2-3, left atrial dilatation were independently associated with the decision to not perform an RHC, while presence of prior venous thromboembolic events or pulmonary arterial hypertension-associated conditions, right atrial dilatation, and tricuspid regurgitation velocity ≥3.7 m/s favor an RHC performance.
Conclusions:
Older age and echocardiographic parameters of left heart disease were independently associated with the decision to not perform an RHC, while presence of prior venous thromboembolic events or pulmonary arterial hypertension-associated conditions, right atrial dilation, and severe PH on echocardiography favored an RHC performance. As such, especially elderly patients may be at an increased risk of diagnostic delays and missed diagnoses of treatable precapillary PH, which could lead to a worse prognosis.




J Am Heart Assoc: 05 Sep 2022:e025143; epub ahead of print
Jansen SMA, Huis In 't Veld AE, Tolen PHCG, Jacobs W, ... de Man FS, Bogaard HJ
J Am Heart Assoc: 05 Sep 2022:e025143; epub ahead of print | PMID: 36062610
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Impact:
Abstract

Sacubitril/Valsartan in Patients With Heart Failure and Concomitant End-Stage Kidney Disease.

Niu CY, Yang SF, Ou SM, Wu CH, ... Lin CC, Li SY

Background:
Heart failure with reduced ejection fraction (HFrEF) is a chronic disease with substantial mortality. Management of HFrEF has seen significant breakthrough after the launch of neprilysin inhibitor. The PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impacton Global Mortality and Morbidity in Heart Failure) trial showed that sacubitril/valsartan significantly reduces HFrEF mortality and the heart failure hospitalization rate. However, in patients with advanced kidney disease, who have the highest prevalence of heart failure, the efficacy and safety of sacubitril/valsartan remains uncertain. We aim to study the efficiency of sacubitril/valsartan in patients with end-stage kidney disease. Methods and Results Heart function was screened by echocardiogram among all patients with end-stage kidney disease in 2 hospitals. Patients with HFrEF received either sacubitril/valsartan or conventional treatment. Fifteen echocardiographic parameters were compared before and after treatment. After 1-year sacubitril/valsartan treatment, parameters of systolic (left ventricular ejection fraction 31.3% to 45.1%, P<0.0001; left ventricular end-systolic volume 95.7 to 70.1 mL, P=0.006; left ventricular internal diameter at end-systole phase 47.2 to 40.1 mm, P=0.005), and diastolic (E/A ratio 1.3 to 0.8, P=0.009; E/Med e\' ratio 25.3 to 18.8, P=0.010) function improved in patients with HFrEF and end-stage kidney disease. These parameters were unchanged in the conventional treatment group. Serum potassium did not increase in the sacubitril/valsartan group.
Conclusions:
Sacubitril/valsartan improves left ventricular systolic and diastolic function in patients with HFrEF and end-stage kidney disease.




J Am Heart Assoc: 05 Sep 2022:e026407; epub ahead of print
Niu CY, Yang SF, Ou SM, Wu CH, ... Lin CC, Li SY
J Am Heart Assoc: 05 Sep 2022:e026407; epub ahead of print | PMID: 36062622
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Impact:
Abstract

Associations of Demographic, Socioeconomic, and Cognitive Characteristics With Mobile Health Access: MESA (Multi-Ethnic Study of Atherosclerosis).

Patel RJS, Ding J, Marvel FA, Shan R, ... Post WS, Martin SS

Background:
Mobile health (mHealth) has an emerging role in the prevention of cardiovascular disease. This study evaluated possible inequities in mHealth access in older adults. Methods and Results mHealth access was assessed from 2019 to 2020 in MESA (Multi-Ethnic Study of Atherosclerosis) telephone surveys of 2796 participants aged 62 to 102 years. A multivariable logistic regression model adjusted for general health status assessed associations of mHealth access measures with relevant demographic, socioeconomic, and cognitive characteristics. There were lower odds of all access measures with older age (odds ratios [ORs], 0.37-0.59 per 10 years) and annual income <$50 000 (versus ≥$50 000 ORs, 0.55-0.62), and higher odds with higher Cognitive Abilities Screening Instrument Score (ORs, 1.22-1.29 per 5 points). Men (versus women) had higher odds of internet access (OR, 1.32 [95% CI,1.05-1.66]) and computing device ownership (OR, 1.31 [95% CI, 1.05-1.63]) but lower fitness tracker ownership odds (OR, 0.70 [95% CI, 0.49-0.89]). For internet access and computing device ownership, we saw lower odds for Hispanic participants (versus White participants OR, 0.61 [95% CI, 0.44-0.85]; OR, 0.69 [95% CI, 0.50-0.95]) and less than a high school education (versus bachelor\'s degree or higher OR, 0.27 [95% CI, 0.18-0.40]; OR, 0.32 [95% CI, 0.28-0.62]). For internet access, lower odds were seen for Black participants (versus White participants OR, 0.64 [95% CI, 0.47-0.86]) and other health insurance (versus health maintenance organization/private OR, 0.59 [95% CI, 0.47-0.74]). Chinese participants (versus White participants) had lower internet access odds (OR, 0.63 [95% CI, 0.44-0.91]) but higher computing device ownership odds (OR, 1.87 [95% CI, 1.28-2.77]).
Conclusions:
Among older-age adults, mHealth access varied by major demographic, socioeconomic, and cognitive characteristics, suggesting a digital divide. Novel mHealth interventions should consider individual access barriers. Registration URL: https://www.clinicaltrials.gov/; Unique identifier: NCT00005487.




J Am Heart Assoc: 03 Sep 2022:e024885; epub ahead of print
Patel RJS, Ding J, Marvel FA, Shan R, ... Post WS, Martin SS
J Am Heart Assoc: 03 Sep 2022:e024885; epub ahead of print | PMID: 36056720
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Impact:
Abstract

Preoperative Short-Term Restriction of Sulfur-Containing Amino Acid Intake for Prevention of Acute Kidney Injury After Cardiac Surgery: A Randomized, Controlled, Double-Blind, Translational Trial.

Osterholt T, Gloistein C, Todorova P, Becker I, ... Grundmann F, Burst V

Background:
Acute kidney injury (AKI) is a major risk factor for chronic kidney disease and increased mortality. Until now, no compelling preventive or therapeutic strategies have been identified. Dietary interventions have been proven highly effective in organ protection from ischemia reperfusion injury in mice and restricting dietary intake of sulfur-containing amino acids (SAA) seems to be instrumental in this regard. The UNICORN trial aimed to evaluate the protective impact of restricting SAA intake before cardiac surgery on incidence of AKI. Methods and Results In this single-center, randomized, controlled, double-blind trial, 115 patients were assigned to a SAA-reduced formula diet (LowS group) or a regular formula diet (control group) in a 1:1 ratio for 7 days before scheduled cardiac surgery. The primary end point was incidence of AKI within 72 hours after surgery, secondary end points included increase of serum creatinine at 24, 48, and 72 hours as well as safety parameters. Quantitative variables were analyzed with nonparametric methods, while categorical variables were evaluated by means of Chi-square or Fisher test. SAA intake in the group with SAA reduced formula diet was successfully reduced by 77% (group with SAA reduced formula diet, 7.37[6.40-7.80] mg/kg per day versus control group, 32.33 [28.92-33.60] mg/kg per day, P<0.001) leading to significantly lower serum levels of methionine. No beneficial effects of SAA restriction on the rate of AKI after surgery could be observed (group with SAA reduced formula diet, 23% versus control group, 16%; P=0.38). Likewise, no differences were recorded with respect to secondary end points (AKI during hospitalization, creatinine at 24, 48, 72 hours after surgery) as well as in subgroup analysis focusing on age, sex, body mass index and diabetes.
Conclusions:
SAA restriction was feasible in the clinical setting but was not associated with protective properties in AKI upon cardiac surgery. Registration URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03715868.




J Am Heart Assoc: 03 Sep 2022:e025229; epub ahead of print
Osterholt T, Gloistein C, Todorova P, Becker I, ... Grundmann F, Burst V
J Am Heart Assoc: 03 Sep 2022:e025229; epub ahead of print | PMID: 36056721
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Impact:
Abstract

Guideline-Recommended Time Less Than 90 Minutes From ECG to Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction Is Associated with Major Survival Benefits, Especially in Octogenarians: A Contemporary Report in 11 226 Patients from NORIC.

Larsen AI, Løland KH, Hovland S, Bleie Ø, ... Uchto M, Rotevatn S

Background:
Using contemporary data from NORIC (Norwegian Registry of Invasive Cardiology) we investigated the predictive value of patient age and time from ECG diagnosis to sheath insertion (ECG-2-sheath) in primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction (STEMI). Methods and Results Data from 11 226 patients collected from all centers offering 24/7/365 primary percutaneous coronary intervention service were explored. For patients aged <80 years the mortality rates were 5.6% and 7.6% at 30 days and 1 year, respectively. For octogenarians the corresponding rates were 15.0% and 24.2%. The Cox hazard ratio was 2.02 (1.93-2.11, P value <0.0001) per 10 years of patient age. Time from ECG-2-sheath was significantly associated with mortality with a 3.6% increase per 30 minutes of time. Using achievement of time goal <90 minutes in patients aged >80 years and mortality at 30 days, mortality was 10.5% and 17.7% for <90 or ≥90 minutes, respectively. The number needed to prevent 1 death was 39 in the whole population and 14 in the elderly. Restricted mean survival gains during median 938 days of follow-up in patients with ECG-2-sheath time <90 minutes were 24 and 76 days for patients aged <80 and ≥80 years, respectively.
Conclusions:
Time from ECG-diagnosis to sheath insertion is strongly correlated with mortality. This applies especially to octogenarians who derive the most in terms of absolute mortality reduction. Registration URL: https://helsedata.no/en/forvaltere/norwegian-institute-of-public-health/norwegian-registry-of-invasive-cardiology/.




J Am Heart Assoc: 03 Sep 2022:e024849; epub ahead of print
Larsen AI, Løland KH, Hovland S, Bleie Ø, ... Uchto M, Rotevatn S
J Am Heart Assoc: 03 Sep 2022:e024849; epub ahead of print | PMID: 36056722
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Impact:
Abstract

EmPHasis-10 Health-Related Quality of Life and Exercise Capacity in Chronic Thromboembolic Pulmonary Hypertension After Balloon Angioplasty.

Sakamoto H, Goda A, Tobita K, Takeuchi K, ... Soejima K, Satoh T

Background:
Whether pulmonary hemodynamic parameters and functional capacity are associated with quality of life in patients with chronic thromboembolic pulmonary hypertension remains unknown. This study aimed to evaluate disease-specific quality of life using the emPHasis-10 questionnaire and assess its determinants in patients with chronic thromboembolic pulmonary hypertension with normalized pulmonary hemodynamics. Methods and Results This cross-sectional study included 187 health status assessments of 143 patients with chronic thromboembolic pulmonary hypertension (median age, 68 [58-75] years; men/women, 51/136; use of home oxygen therapy, 51 patients [27%]) after balloon pulmonary angioplasty with normalized mean pulmonary artery pressure <25 mm Hg at rest. Right heart catheterization was performed, followed by assessment of 6-minute walk distance and the emPHasis-10 questionnaire. The median pulmonary artery pressure and pulmonary vascular resistance were 18 (15-21) mm Hg and 2.2 (1.7-2.9) wood units, respectively. The median emPHasis-10 score was 14 (8-24), whereas the median 6-minute walk distance was 447 (385-517) m. Univariate linear regression analysis showed that the emPHasis-10 score was associated with 6-minute walk distance (β=-0.476 [95% CI -0.604, -0.348], P<0.001) and home oxygen therapy (β=0.214 [95% CI, 0.072, 0.356], P=0.003) but not with hemodynamic parameters. Multiple regression analysis revealed that a higher emPHasis-10 score was associated with lower 6-minute walk distance (β=-0.475 [95% CI, -0.631 to -0.319], P<0.001).
Conclusions:
Health-related quality of life was associated with exercise capacity and the use of home oxygen therapy, but not with hemodynamic parameters, in patients with chronic thromboembolic pulmonary hypertension and normalized hemodynamics after balloon pulmonary angioplasty. Improvements in exercise capacity may lead to further improvements in quality of life.




J Am Heart Assoc: 03 Sep 2022:e026400; epub ahead of print
Sakamoto H, Goda A, Tobita K, Takeuchi K, ... Soejima K, Satoh T
J Am Heart Assoc: 03 Sep 2022:e026400; epub ahead of print | PMID: 36056723
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Impact:
Abstract

Factors Contributing to Sex Differences in Health-Related Quality of Life After Ischemic Stroke: BASIC (Brain Attack Surveillance in Corpus Christi) Project.

Phan HT, Reeves MJ, Gall S, Morgenstern LB, Xu Y, Lisabeth LD

Background:
Women have been reported to have worse health-related quality of life (HRQoL) following stroke than men, but uncertainty exists over the reasons for the sex difference. Methods and Results We included all ischemic strokes registered with the BASIC (Brain Attack Surveillance in Corpus Christi) project (May 2010-December 2016), a population-based stroke study, who completed a 90-day outcome interview. Information on baseline characteristics was obtained from medical records and in-person interviews. HRQoL was measured by the 12-item short-form Stroke Specific Quality of Life Scale. Multivariable Tobit regression was used to estimate the mean difference in overall HRQoL scores (range, 1-5; higher indicating better HRQoL) between sexes and to identify contributing factors to the differences. We included 1061 cases with complete data on HRQoL and covariates (median age, 67 years; 51% women). In unadjusted analyses, women had poorer overall HRQoL than men (mean difference, -0.26 [95% CI, -0.40 to -0.13]). Contributors to this difference included sociodemographic/prestroke factors (eg, age, race and ethnicity, prestroke function), risk factors/comorbidities (eg, history of stroke, Alzheimer disease/dementia), and initial stroke severity. Sociodemographic/prestroke factors explained 62% of the sex difference (mean difference, -0.08 [95% CI, -0.21 to 0.04]). In a fully adjusted model that included adjustment for all confounding factors, the sex difference was eliminated and became nonsignificant (mean difference, -0.03 [95% CI, -0.16 to 0.09]).
Conclusions:
Poorer HRQoL in women compared with men was observed and explained by the combination of sociodemographic and prestroke factors, including physical function before stroke and stroke severity. The findings suggest potential subgroups of women who might benefit from more targeted interventions before and after stroke to improve HRQoL.




J Am Heart Assoc: 03 Sep 2022:e026123; epub ahead of print
Phan HT, Reeves MJ, Gall S, Morgenstern LB, Xu Y, Lisabeth LD
J Am Heart Assoc: 03 Sep 2022:e026123; epub ahead of print | PMID: 36056724
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Impact:
Abstract

Prediction of Cardiovascular Events by Pulse Waveform Parameters: Analysis of CARTaGENE.

Desbiens LC, Fortier C, Nadeau-Fredette AC, Madore F, ... Agharazii M, Goupil R

Background:
Waveform parameters provide approximate data about aortic wave reflection. However, their association with cardiovascular events remains controversial and their role in cardiovascular prediction is unknown. Methods and Results We analyzed participants aged between 40 and 69 from the population-based CARTaGENE cohort. Baseline pulse wave analysis (central pulse pressure, augmentation index) and wave separation analysis (forward pressure, backward pressure, reflection magnitude) parameters were derived from radial artery tonometry. Associations between each parameter and major adverse atherosclerotic events (MACE; cardiovascular death, stroke, myocardial infarction) were obtained using adjusted Cox models. The incremental predictive value of each parameter compared with the 10-year atherosclerotic cardiovascular disease score alone was assessed using hazard ratios, c-index differences, continuous net reclassification indexes, and integrated discrimination indexes. From 17 561 eligible patients, 2315 patients had a MACE during a median follow-up of 10.1 years. Central pulse pressure, forward pressure, and backward pressure, but not augmentation index and reflection magnitude, were significantly associated with MACE after full adjustment. All parameters except forward pressure statistically improved MACE prediction compared with the atherosclerotic cardiovascular disease score alone. The greatest prediction improvement was seen with augmentation index and reflection magnitude but remained small in magnitude. These 2 parameters enhanced predictive performance more strongly in patients with low baseline atherosclerotic cardiovascular disease scores. Up to 5.7% of individuals were reclassified into a different risk stratum by adding waveform parameters to atherosclerotic cardiovascular disease scores.
Conclusions:
Some waveform parameters are independently associated with MACEs in a population-based cohort. Augmentation index and reflection magnitude slightly improve risk prediction, especially in patients at low cardiovascular risk.




J Am Heart Assoc: 03 Sep 2022:e026603; epub ahead of print
Desbiens LC, Fortier C, Nadeau-Fredette AC, Madore F, ... Agharazii M, Goupil R
J Am Heart Assoc: 03 Sep 2022:e026603; epub ahead of print | PMID: 36056725
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Impact:
Abstract

Government Regulation and Percutaneous Coronary Intervention Volume, Access and Outcomes: Insights From the Washington State Cardiac Care Outcomes Assessment Program.

Kataruka A, Maynard CC, Hira RS, Dean L, ... Ring ME, Doll JA

Background:
It is unclear how to geographically distribute percutaneous coronary intervention (PCI) programs to optimize patient outcomes. The Washington State Certificate of Need program seeks to balance hospital volume and patient access through regulation of elective PCI. Methods and Results We performed a retrospective cohort study of all non-Veterans Affairs hospitals with PCI programs in Washington State from 2009 to 2018. Hospitals were classified as having (1) full PCI services and surgical backup (legacy hospitals, n=17); (2) full services without surgical backup (new certificate of need [CON] hospitals, n=9); or (3) only nonelective PCI without surgical backup (myocardial infarction [MI] access hospitals, n=9). Annual median hospital-level volumes were highest at legacy hospitals (605, interquartile range, 466-780), followed by new CON, (243, interquartile range, 146-287) and MI access, (61, interquartile range, 23-145). Compared with MI access hospitals, risk-adjusted mortality for nonelective patients was lower for legacy (odds ratio [OR], 0.59 [95% CI, 0.48-0.72]) and new-CON hospitals (OR, 0.55 [95% CI, 0.45-0.65]). Legacy hospitals provided access within 60 minutes for 90% of the population; addition of new CON and MI access hospitals resulted in only an additional 1.5% of the population having access within 60 minutes.
Conclusions:
Many PCI programs in Washington State do not meet minimum volume standards despite regulation designed to consolidate elective PCI procedures. This CON strategy has resulted in a tiered system that includes low-volume centers treating high-risk patients with poor outcomes, without significant increase in geographic access. CON policies should re-evaluate the number and distribution of PCI programs.




J Am Heart Assoc: 03 Sep 2022:e025607; epub ahead of print
Kataruka A, Maynard CC, Hira RS, Dean L, ... Ring ME, Doll JA
J Am Heart Assoc: 03 Sep 2022:e025607; epub ahead of print | PMID: 36056726
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Impact:
Abstract

Mouse Model of Heart Failure With Preserved Ejection Fraction Driven by Hyperlipidemia and Enhanced Cardiac Low-Density Lipoprotein Receptor Expression.

Williams M, Capcha JMC, Irion CI, Seo G, ... Hare JM, Shehadeh LA

Background:
The pathways of diastolic dysfunction and heart failure with preserved ejection fraction driven by lipotoxicity with metabolic syndrome are incompletely understood. Thus, there is an urgent need for animal models that accurately mimic the metabolic and cardiovascular phenotypes of this phenogroup for mechanistic studies. Methods and Results Hyperlipidemia was induced in WT-129 mice by 4 weeks of biweekly poloxamer-407 intraperitoneal injections with or without a single intravenous injection of adeno-associatedvirus 9-cardiac troponin T-low-density lipoprotein receptor (n=31), or single intravenous injection with adeno-associatedvirus 9-cardiac troponin T-low-density lipoprotein receptor alone (n=10). Treatment groups were compared with untreated or placebo controls (n=37). Echocardiography, blood pressure, whole-body plethysmography, ECG telemetry, activity wheel monitoring, and biochemical and histological changes were assessed at 4 to 8 weeks. At 4 weeks, double treatment conferred diastolic dysfunction, preserved ejection fraction, and increased left ventricular wall thickness. Blood pressure and whole-body plethysmography results were normal, but respiration decreased at 8 weeks (P<0.01). ECG and activity wheel monitoring, respectively, indicated heart block and decreased exercise activity (P<0.001). Double treatment promoted elevated myocardial lipids including total cholesterol, fibrosis, increased wet/dry lung (P<0.001) and heart weight/body weight (P<0.05). Xanthelasma, ascites, and cardiac ischemia were evident in double and single (p407) groups. Sudden death occurred between 6 and 12 weeks in double and single (p407) treatment groups.
Conclusions:
We present a novel model of heart failure with preserved ejection fraction driven by dyslipidemia where mice acquire diastolic dysfunction, arrhythmia, cardiac hypertrophy, fibrosis, pulmonary congestion, exercise intolerance, and preserved ejection fraction in the absence of obesity, hypertension, kidney disease, or diabetes. The model can be applied to dissect pathways of metabolic syndrome that drive diastolic dysfunction in this lipotoxicity-mediated heart failure with preserved ejection fraction phenogroup mimic.




J Am Heart Assoc: 03 Sep 2022:e027216; epub ahead of print
Williams M, Capcha JMC, Irion CI, Seo G, ... Hare JM, Shehadeh LA
J Am Heart Assoc: 03 Sep 2022:e027216; epub ahead of print | PMID: 36056728
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Impact:
Abstract

Laboratory Test Predictors for Major Bleeding in Elderly (≥80 Years) Patients With Nonvalvular Atrial Fibrillation Treated With Edoxaban 15 mg: Sub-Analysis of the ELDERCARE-AF Trial.

Mikami T, Hirabayashi K, Okawa K, Betsuyaku T, ... Yamashita T, Okumura K

Background:
We investigated the predictors related to major bleeding events during treatment with edoxaban 15 mg in patients aged ≥80 years with nonvalvular atrial fibrillation and high bleeding risk, for whom standard oral anticoagulants are inappropriate, focusing on standard laboratory tests related to bleeding. Methods and Results This was a prespecified subanalysis of the on-treatment analysis set of the ELDERCARE-AF (Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients) trial. Major bleeding was the primary safety end point. The event rates were calculated according to prespecified characteristics at baseline. A total of 984 Japanese patients were randomly assigned to edoxaban 15 mg or placebo (n=492, each). During the study period, 20 and 11 major bleeding events occurred in the edoxaban and placebo groups, respectively. The adjusted analysis revealed that hemoglobin <12.3 g/dL (adjusted hazard ratio [aHR], 3.57 [95% CI, 1.10-11.55]) and prothrombin time ≥12.7 seconds; (aHR, 2.89 [95% CI, 1.05-8.02]) independently predicted major bleeding, while creatinine clearance <30 mL/min showed a tendency towards an increase in major bleeding (aHR, 2.68; 95% CI, 0.96-7.46). In patients treated with edoxaban lacking these 3 risk factors, no major bleeding occurred; major bleeding event rates increased with each risk factor. Patients with 3 risk factors were significantly more likely to have a major bleeding event at 11.05%/year (HR, 7.15 [95% CI, 1.92-26.71]).
Conclusions:
In elderly patients with nonvalvular atrial fibrillation with high bleeding risk, baseline hemoglobin <12.3 g/dL, prothrombin time ≥12.7 seconds, and creatinine clearance <30 mL/min may predict major bleeding during treatment with edoxaban 15 mg. Registration URL: ELDERCARE-AF https://www.clinicaltrials.gov; Unique number: NCT02801669.




J Am Heart Assoc: 03 Sep 2022:e024970; epub ahead of print
Mikami T, Hirabayashi K, Okawa K, Betsuyaku T, ... Yamashita T, Okumura K
J Am Heart Assoc: 03 Sep 2022:e024970; epub ahead of print | PMID: 36056729
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Impact:
Abstract

Stroke-Heart Syndrome: Recent Advances and Challenges.

Scheitz JF, Sposato LA, Schulz-Menger J, Nolte CH, Backs J, Endres M
After ischemic stroke, there is a significant burden of cardiovascular complications, both in the acute and chronic phase. Severe adverse cardiac events occur in 10% to 20% of patients within the first few days after stroke and comprise a continuum of cardiac changes ranging from acute myocardial injury and coronary syndromes to heart failure or arrhythmia. Recently, the term stroke-heart syndrome was introduced to provide an integrated conceptual framework that summarizes neurocardiogenic mechanisms that lead to these cardiac events after stroke. New findings from experimental and clinical studies have further refined our understanding of the clinical manifestations, pathophysiology, and potential long-term consequences of the stroke-heart syndrome. Local cerebral and systemic mediators, which mainly involve autonomic dysfunction and increased inflammation, may lead to altered cardiomyocyte metabolism, dysregulation of (tissue-resident) leukocyte populations, and (micro-) vascular changes. However, at the individual patient level, it remains challenging to differentiate between comorbid cardiovascular conditions and stroke-induced heart injury. Therefore, further research activities led by joint teams of basic and clinical researchers with backgrounds in both cardiology and neurology are needed to identify the most relevant therapeutic targets that can be tested in clinical trials.



J Am Heart Assoc: 03 Sep 2022:e026528; epub ahead of print
Scheitz JF, Sposato LA, Schulz-Menger J, Nolte CH, Backs J, Endres M
J Am Heart Assoc: 03 Sep 2022:e026528; epub ahead of print | PMID: 36056731
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Impact:
Abstract

Bereavement and Prognosis After a First Acute Myocardial Infarction: A Swedish Register-Based Cohort Study.

Wei D, Janszky I, Ljung R, Fang F, Li J, László KD

Background:
Despite accumulating evidence suggesting that bereavement is associated with increased risks of cardiovascular morbidity and mortality, the association between bereavement and prognosis after acute myocardial infarction (AMI) has not been well documented. We investigated the association by using Swedish register data.
Methods and results:
We studied 266 651 patients with a first AMI included in the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) quality register from 1991 to 2018. We obtained information on bereavement (ie, death of a partner, child, grandchild, sibling, or parent), on primary (nonfatal recurrent AMI and death attributed to ischemic heart disease) and secondary outcomes (total mortality, heart failure, and stroke) and on covariates from several national registers. The association was analyzed using Poisson regression. The bereaved patients had a slightly increased risk of the primary outcome; the corresponding risk ratio (RR) was 1.02 (95% CI, 1.00-1.04). An increased risk was noted any time bereavement occurred, except if the loss was in the year after the first AMI. The association was strongest for the loss of a partner, followed by the loss of a child, grandchild, sibling, or parent. We also observed increased risks for total mortality (RR, 1.14 [95% CI, 1.12-1.16]), heart failure (RR, 1.05 [95% CI, 1.02-1.08]), and stroke (RR, 1.09 [95% CI, 1.05-1.13]) following bereavement. CONCLUSIONS Bereavement was associated with an increased risk of poor prognosis after a first AMI. The association varied by the relationship to the deceased.




J Am Heart Assoc: 03 Sep 2022:e027143; epub ahead of print
Wei D, Janszky I, Ljung R, Fang F, Li J, László KD
J Am Heart Assoc: 03 Sep 2022:e027143; epub ahead of print | PMID: 36056733
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Abstract

Patent Ductus Arteriosus: A Contemporary Perspective for the Pediatric and Adult Cardiac Care Provider.

Backes CH, Hill KD, Shelton EL, Slaughter JL, ... Benitz WE, Garg V
The burden of patent ductus arteriosus (PDA) continues to be significant. In view of marked differences in preterm infants versus more mature, term counterparts (viewed on a continuum with adolescent and adult patients), mechanisms regulating ductal patency, genetic contributions, clinical consequences, and diagnostic and treatment thresholds are discussed separately, when appropriate. Among both preterm infants and older children and adults, a range of hemodynamic profiles highlighting the markedly variable consequences of the PDA are provided. In most contemporary settings, transcatheter closure is preferable over surgical ligation, but data on longer-term outcomes, particularly among preterm infants, are lacking. The present review provides recommendations to identify gaps in PDA diagnosis, management, and treatment on which subsequent research can be developed. Ultimately, the combination of refined diagnostic thresholds and expanded treatment options provides the best opportunities to address the burden of PDA. Although fundamental gaps remain unanswered, the present review provides pediatric and adult cardiac care providers with a contemporary framework in PDA care to support the practice of evidence-based medicine.



J Am Heart Assoc: 03 Sep 2022:e025784; epub ahead of print
Backes CH, Hill KD, Shelton EL, Slaughter JL, ... Benitz WE, Garg V
J Am Heart Assoc: 03 Sep 2022:e025784; epub ahead of print | PMID: 36056734
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Abstract

Global Burden, Regional Differences, Trends, and Health Consequences of Medication Nonadherence for Hypertension During 2010 to 2020: A Meta-Analysis Involving 27 Million Patients.

Lee EKP, Poon P, Yip BHK, Bo Y, ... Wong MCS, Wong SYS

Background:
Nonadherence to antihypertensive medications is the leading cause of poor blood pressure control and thereby cardiovascular diseases and mortality worldwide. Methods and Results We investigated the global epidemiology, regional differences, and trend of antihypertensive medication nonadherence via a systematic review and meta-analyses of data from 2010 to 2020. Multiple medical databases and clinicaltrials.gov were searched for articles. Observational studies reporting the proportion of patients with anti-hypertensive medication nonadherence were included. The proportion of nonadherence, publication year, year of first recruitment, country, and health outcomes attributable to antihypertensive medication nonadherence were extracted. Two reviewers screened abstracts and full texts, classified countries according to levels of income and locations, and extracted data. The Joanna Briggs Institute prevalence critical appraisal tool was used to rate the included studies. Prevalence meta-analyses were conducted using a fixed-effects model, and trends in prevalence were analyzed using meta-regression. The certainty of evidence concerning the effect of health consequences of nonadherence was rated according to Grading of Recommendations, Assessment, Development and Evaluations. A total of 161 studies were included. Subject to different detection methods, the global prevalence of anti-hypertensive medication nonadherence was 27% to 40%. Nonadherence was more prevalent in low- to middle-income countries than in high-income countries, and in non-Western countries than in Western countries. No significant trend in prevalence was detected between 2010 and 2020. Patients with antihypertensive medication nonadherence had suboptimal blood pressure control, complications from hypertension, all-cause hospitalization, and all-cause mortality.
Conclusions:
While high prevalence of anti-hypertensive medication nonadherence was detected worldwide, higher prevalence was detected in low- to middle-income and non-Western countries. Interventions are urgently required, especially in these regions. Current evidence is limited by high heterogeneity. Registration URL: www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021259860.




J Am Heart Assoc: 03 Sep 2022:e026582; epub ahead of print
Lee EKP, Poon P, Yip BHK, Bo Y, ... Wong MCS, Wong SYS
J Am Heart Assoc: 03 Sep 2022:e026582; epub ahead of print | PMID: 36056737
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Abstract

Incidence and Predictors of Adverse Events Among Initially Stable ST-Elevation Myocardial Infarction Patients Following Primary Percutaneous Coronary Intervention.

Amon J, Wong GC, Lee T, Singer J, ... van Diepen S, Fordyce CB

Background:
Cardiac intensive care units were originally created in the prerevascularization era for the early recognition of ventricular arrhythmias following a myocardial infarction. Many patients with stable ST-segment-elevation myocardial infarction (STEMI) are still routinely triaged to cardiac intensive care units after a primary percutaneous coronary intervention (pPCI), independent of clinical risk or the provision of critical care therapies. The aim of this study was to determine factors associated with in-hospital adverse events in a hemodynamically stable, postreperfusion population of patients with STEMI. Methods and Results Between April 2012 and November 2019, 2101 consecutive patients with STEMI who received pPCI in the Vancouver Coastal Health Authority were evaluated. Patients were stratified into those with and without subsequent adverse events, which were defined as cardiogenic shock, in-hospital cardiac arrest, stroke, re-infarction, and death. Multivariable logistic regression models were used to determine predictors of adverse events. After excluding patients presenting with cardiac arrest, cardiogenic shock, or heart failure, the final analysis cohort comprised 1770 stable patients with STEMI who had received pPCI. A total of 94 (5.3%) patients developed at least one adverse event: cardiogenic shock 55 (3.1%), in-hospital cardiac arrest 42 (2.4%), death 28 (1.6%), stroke 21 (1.2%), and re-infarction 5 (0.3%). Univariable predictors of adverse events were older age, female sex, prior stroke, chronic kidney disease, and atrial fibrillation. There was no significant difference in reperfusion times between those with and without adverse events. Following multivariable adjustment, moderate to severe chronic kidney disease (creatinine clearance <44 mL/min; 13% of cohort) was associated with adverse events (odds ratio 2.24 [95% CI, 1.12-4.48]) independent of reperfusion time, age, sex, smoking status, hypertension, diabetes, and prior myocardial infarction/PCI/coronary artery bypass grafting.
Conclusions:
Only 1 in 20 initially stable patients with STEMI receiving pPCI developed an in-hospital adverse event. Moderate to severe chronic kidney disease independently predicted the risk of future adverse events. These results indicate that the majority of patients with STEMI who receive pPCI may not require routine admission to a cardiac intensive care unit following reperfusion.




J Am Heart Assoc: 03 Sep 2022:e025572; epub ahead of print
Amon J, Wong GC, Lee T, Singer J, ... van Diepen S, Fordyce CB
J Am Heart Assoc: 03 Sep 2022:e025572; epub ahead of print | PMID: 36056738
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Abstract

Alert-Triggered Patient Education Versus Nurse Feedback for Nonadministered Venous Thromboembolism Prophylaxis Doses: A Cluster-Randomized Controlled Trial.

Haut ER, Owodunni OP, Wang J, Shaffer DL, ... Streiff MB, Lau BD

Background:
Many hospitalized patients are not administered prescribed doses of pharmacologic venous thromboembolism prophylaxis. Methods and Results In this cluster-randomized controlled trial, all adult non-intensive care units (10 medical, 6 surgical) in 1 academic hospital were randomized to either a real-time, electronic alert-triggered, patient-centered education bundle intervention or nurse feedback intervention to evaluate their effectiveness for reducing nonadministration of venous thromboembolism prophylaxis. Primary outcome was the proportion of nonadministered doses of prescribed pharmacologic prophylaxis. Secondary outcomes were proportions of nonadministered doses stratified by nonadministration reasons (patient refusal, other). To test our primary hypothesis that both interventions would reduce nonadministration, we compared outcomes pre- versus postintervention within each cohort. Secondary hypotheses were tested comparing the effectiveness between cohorts. Of 11 098 patient visits, overall dose nonadministration declined significantly after the interventions (13.4% versus 9.2%; odds ratio [OR], 0.64 [95% CI, 0.57-0.71]). Nonadministration decreased significantly (P<0.001) in both arms: patient-centered education bundle, 12.2% versus 7.4% (OR, 0.56 [95% CI, 0.48-0.66]), and nurse feedback, 14.7% versus 11.2% (OR, 0.72 [95% CI, 0.62-0.84]). Patient refusal decreased significantly in both arms: patient-centered education bundle, 7.3% versus 3.7% (OR, 0.46 [95% CI, 0.37-0.58]), and nurse feedback, 9.5% versus 7.1% (OR, 0.71 [95% CI, 0.59-0.86]). No differential effect occurred on medical versus surgical units. The patient-centered education bundle was significantly more effective in reducing all nonadministered (P=0.03) and refused doses (P=0.003) compared with nurse feedback (OR, 1.28 [95% CI, 1.0-1.61]; P=0.03 for interaction).
Conclusions:
Information technology strategies like the alert-triggered, targeted patient-centered education bundle, and nurse-focused audit and feedback can improve venous thromboembolism prophylaxis administration. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03367364.




J Am Heart Assoc: 01 Sep 2022:e027119; epub ahead of print
Haut ER, Owodunni OP, Wang J, Shaffer DL, ... Streiff MB, Lau BD
J Am Heart Assoc: 01 Sep 2022:e027119; epub ahead of print | PMID: 36047732
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Impact:
Abstract

Physical Function and Subsequent Risk of Cardiovascular Events in Older Adults: The Atherosclerosis Risk in Communities Study.

Hu X, Mok Y, Ding N, Sullivan KJ, ... Palta P, Matsushita K

Background:
Reduced physical function, a representative phenotype of aging, has been associated with cardiovascular disease (CVD). However, few studies have comprehensively investigated its association with composite and individual CVD outcomes in community-dwelling older adults and its predictive value for CVD beyond traditional risk factors. Methods and Results We studied 5570 participants (mean age 75 [SD 5] years, female 58%, Black 22%) at visit 5 (2011-2013) of the ARIC (Atherosclerosis Risk in Communities) study. Physical function was evaluated with the Short Physical Performance Battery (SPPB), which incorporates a walk test, chair stands, and balance tests. The SPPB score was modeled categorically (low [0-6], intermediate [7-9], and high [10-12]) and continuously. We assessed the associations of SPPB score with subsequent composite (coronary heart disease, stroke, or heart failure) and individual CVD outcomes (components within composite outcome) using multivariable Cox models adjusting for major CVD risk factors and history of CVD. We also evaluated improvement in C-statistics by adding SPPB to traditional CVD risk factors in the Pooled Cohort Equation. Among the study participants, 13% had low, 30% intermediate, and 57% high SPPB scores. During a median follow-up of 7.0 (interquartile interval 5.3-7.8) years, there were 930 composite CVD events (386 coronary heart disease, 251 stroke, and 529 heart failure cases). The hazard ratios of composite CVD in low and intermediate versus high SPPB score were 1.47 (95% CI, 1.20-1.79) and 1.25 (95% CI, 1.07-1.46), respectively, after adjusting for potential confounders. Continuous SPPB score demonstrated independent associations with each CVD outcome. The associations were largely consistent across subgroups (including participants with prevalent CVD at baseline). The addition of SPPB to traditional CVD risk factors significantly improved the C-statistics of CVD outcomes (eg, ΔC-statistic 0.019 [95% CI, 0.011-0.027] for composite CVD).
Conclusions:
Reduced physical function was independently associated with the risk of composite and individual CVD outcomes and improved their risk prediction beyond traditional risk factors in community-dwelling older adults. Although confirmatory studies are needed, our results suggest the potential usefulness of SPPB for classifying CVD risk in older adults.




J Am Heart Assoc: 31 Aug 2022:e025780; epub ahead of print
Hu X, Mok Y, Ding N, Sullivan KJ, ... Palta P, Matsushita K
J Am Heart Assoc: 31 Aug 2022:e025780; epub ahead of print | PMID: 36043511
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Abstract

Shift Work and the Risk of Cardiometabolic Multimorbidity Among Patients With Hypertension: A Prospective Cohort Study of UK Biobank.

Yang L, Luo Y, He L, Yin J, ... Cheng X, Bai Y

Background:
Although the association between shift work and individual cardiometabolic diseases has been well studied, its role in the progression to cardiometabolic multimorbidity (CMM) remains unclear. In this study, we investigate the association between shift work and the incidence of CMM in patients with hypertension. Methods and Results This study is a population-based and prospective cohort study on 36 939 UK Biobank participants. We used competing risk models to examine the association between shift work and the risk of CMM, which was defined as coexistence of hypertension and diabetes, coronary heart disease, or stroke in our study. We also investigated the association between the frequency and duration of shift work and CMM risks. In addition, we conducted a cross-classification analysis with the combination of frequency and duration of shift work, chronotype and sleep duration as the exposure metrics. During a median follow-up of 11.6 years, a total of 5935 participants developed CMM. We found that usually/always night shift workers were associated with a 16% higher risk of CMM compared with day workers (hazard ratio [HR], 1.16 [95% CI, 1.02-1.31]). We also found that a higher frequency of night shifts (>10/month) was associated with increased risk of CMM (HR, 1.19 [95% CI, 1.06-1.34]) that was more pronounced for >10/month in combination with a morning chronotype or <7 hours or >8 hours of sleep duration (HR, 1.26 [95% CI, 1.02-1.56]; HR, 1.43 [95% CI, 1.19-1.72], respectively).
Conclusions:
We find that night shift work is associated with higher CMM risk in patients with hypertension.




J Am Heart Assoc: 29 Aug 2022:e025936; epub ahead of print
Yang L, Luo Y, He L, Yin J, ... Cheng X, Bai Y
J Am Heart Assoc: 29 Aug 2022:e025936; epub ahead of print | PMID: 36036170
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Impact:
Abstract

ECG T-Wave Morphologic Variations Predict Ventricular Arrhythmic Risk in Low- and Moderate-Risk Populations.

Ramírez J, Kiviniemi A, van Duijvenboden S, Tinker A, ... Orini M, Munroe PB

Background:
Early identification of individuals at risk of sudden cardiac death (SCD) remains a major challenge. The ECG is a simple, common test, with potential for large-scale application. We developed and tested the predictive value of a novel index quantifying T-wave morphologic variations with respect to a normal reference (TMV), which only requires one beat and a single-lead ECG. Methods and Results We obtained reference T-wave morphologies from 23 962 participants in the UK Biobank study. With Cox models, we determined the association between TMV and life-threatening ventricular arrhythmia in an independent data set from UK Biobank study without a history of cardiovascular events (N=51 794; median follow-up of 122 months) and SCD in patients with coronary artery disease from ARTEMIS (N=1872; median follow-up of 60 months). In UK Biobank study, 220 (0.4%) individuals developed life-threatening ventricular arrhythmias. TMV was significantly associated with life-threatening ventricular arrhythmias (hazard ratio [HR] of 1.13 per SD increase [95% CI, 1.03-1.24]; P=0.009). In ARTEMIS, 34 (1.8%) individuals reached the primary end point. Patients with TMV ≥5 had an HR for SCD of 2.86 (95% CI, 1.40-5.84; P=0.004) with respect to those with TMV <5, independently from QRS duration, corrected QT interval, and left ventricular ejection fraction. TMV was not significantly associated with death from a cause other than SCD.
Conclusions:
TMV identifies individuals at life-threatening ventricular arrhythmia and SCD risk using a single-beat single-lead ECG, enabling inexpensive, quick, and safe risk assessment in large populations.




J Am Heart Assoc: 29 Aug 2022:e025897; epub ahead of print
Ramírez J, Kiviniemi A, van Duijvenboden S, Tinker A, ... Orini M, Munroe PB
J Am Heart Assoc: 29 Aug 2022:e025897; epub ahead of print | PMID: 36036209
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Abstract

Incidence, Characteristics, and Outcomes of Ventricular Fibrillation Complicating Acute Myocardial Infarction in Women Admitted Alive in the Hospital.

Weizman O, Marijon E, Narayanan K, Boveda S, ... Danchin N, FAST‐MI Program Investigators

Background:
Little data are available in women presenting with ventricular fibrillation (VF) in the setting of acute myocardial infarction (AMI). We assessed frequency, predictors of VF, and outcomes, with a special focus on women compared with men. Methods and Results Data were analyzed from the FAST-MI (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction) program, which prospectively included 14 406 patients admitted to French cardiac intensive care units ≤48 hours from AMI onset between 1995 and 2015 (mean age, 66±14 years; 72% men; mean left ventricular ejection fraction, 52±12%; 59% with ST-segment-elevation myocardial infarction). A total of 359 patients developed VF during AMI, including 81 women (2.0% of 4091 women) and 278 men (2.7% of 10 315 men, P=0.02). ST-segment-elevation myocardial infarction (odds ratio [OR], 2.29 [95% CI, 1.75-2.99]; P<0.001) was independently associated with the onset of VF during AMI. In contrast, female sex (OR, 0.73 [95% CI, 0.56-0.95]; P=0.02), hypertension (OR, 0.75 [95% CI, 0.60-0.94]; P=0.01), and prior myocardial infarction (OR, 0.69 [95% CI, 0.50-0.96]; P=0.03) were protective factors. Women were less likely to have cardiac intervention than men (percutaneous coronary intervention during hospitalization 48.1% versus 66.9%, respectively; P=0.04) with a higher 1-year mortality in women compared with men (50.6% versus 37.4%, respectively; P=0.03), including increased in-hospital mortality (42.0% versus 32.7%, respectively; P=0.12). After adjustment, female sex was no longer associated with a worse 1-year mortality (adjusted hazard ratio, 1.10 [95% CI, 0.75-1.61]; P=0.63).
Conclusions:
Women have lower risk of developing VF during AMI compared with men. However, they are less likely to receive cardiac interventions than men, possibly contributing to missed opportunities of improved outcomes.




J Am Heart Assoc: 26 Aug 2022:e025959; epub ahead of print
Weizman O, Marijon E, Narayanan K, Boveda S, ... Danchin N, FAST‐MI Program Investigators
J Am Heart Assoc: 26 Aug 2022:e025959; epub ahead of print | PMID: 36017613
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Impact:
Abstract

Role of Renin-Angiotensin-Aldosterone System Inhibition in Patients Undergoing Carotid Revascularization.

Elsayed N, Unkart J, Abdelgawwad M, Naazie I, Lawrence PF, Malas MB

Background:
Previous data suggest that using renin-angiotensin-aldosterone system inhibitors (RAASIs) improves survival in patients with cardiovascular diseases. We sought to investigate the association of different patterns of use of RAASIs on perioperative and 1-year outcomes following carotid revascularization. Methods and Results We investigated patients undergoing carotid revascularization, either with carotid endarterectomy or transfemoral carotid artery stenting, in the VQI (Vascular Quality Initiative) VISION (Vascular Implant Surveillance and Interventional Outcomes Network) data set between 2003 and 2018. We divided our cohort into 3 groups: (1) no history of RAASI intake, (2) preoperative intake only, and (3) continuous pre- and postoperative intake. The final cohort included 73 174 patients; 44.4% had no intake, 50% had continuous intake, and 5.6% had only preoperative intake. Compared with continuous intake, preoperative and no intake were associated with higher odds of postoperative stroke (odds ratio [OR], 1.7 [95% CI, 1.5-1.9]; P<0.001; OR, 1.1 [95% CI, 1.03-1.2]; P=0.010); death (OR, 4.8 [95% CI, 3.8-6.1]; P<0.001; OR, 1.9 [95% CI, 1.6-2.2]; P<0.001); and stroke/death (OR, 2.05 [95% CI, 1.8-2.3]; P<0.001; OR, 1.2 [95% CI, 1.1-1.3]; P<0.001), respectively. At 1 year, preoperative and no intake were associated with higher odds of stroke (hazard ratio [HR], 1.4 [95% CI, 1.3-1.6]; P<0.001; HR, 1.15, [95% CI, 1.08-1.2]; P<0.001); death (HR, 1.7 [95% CI, 1.5-1.9]; P<0.001; HR, 1.3 [95% CI, 1.2-1.4]; P<0.001); and stroke/death (HR, 1.5 [95% CI, 1.4-1.7]; P<0.001; HR, 1.2 [95% CI, 1.17-1.3]; P<0.001), respectively.
Conclusions:
Compared with subjects discontinuing or never starting RAASIs, use of RAASIs before and after carotid revascularization was associated with a short-term stroke and mortality benefit. Future clinical trials examining prescribing patterns of RAASIs should aim to clarify the timing and potential to maximize the protective effects of RAASIs in high-risk vascular patients.




J Am Heart Assoc: 24 Aug 2022:e025034; epub ahead of print
Elsayed N, Unkart J, Abdelgawwad M, Naazie I, Lawrence PF, Malas MB
J Am Heart Assoc: 24 Aug 2022:e025034; epub ahead of print | PMID: 36000412
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Abstract

Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Valve Replacement or Repair.

Mentias A, Saad M, Michael M, Nakhla S, ... Desai MY, Kapadia S

Background:
We sought to examine outcomes of direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation with valve repair/replacement. Methods and Results Two atrial fibrillation cohorts from Medicare were identified from 2015 to 2019. They comprised patients who underwent surgical or transcatheter mitral valve repair (MV repair cohort) and surgical aortic or mitral bioprosthetic or transcatheter aortic valve replacement (bioprosthetic cohort). Each cohort was divided into warfarin and DOACs (apixaban, rivaroxaban, and dabigatran) groups. Study outcomes included mortality, stroke, and major bleeding. Inverse probability weighting was used for adjustment between the 2 groups in each cohort. The MV repair cohort included 1178 patients. After a median of 468 days, DOACs were associated with lower risk of mortality (hazard ratio [HR], 0.67 [95% CI, 0.55-0.82], P<0.001), ischemic stroke (HR, 0.72 [95% CI, 0.52-1.00], P=0.05) and bleeding (HR, 0.79 [95% CI, 0.63-0.99], P=0.04) compared with warfarin. The bioprosthetic cohort included 8089 patients. After a median follow-up of 413 days, DOACs were associated with similar risk of mortality (adjusted HR, 0.93 [95% CI, 0.86-1.01], P=0.08), higher risk of ischemic stroke (adjusted HR, 1.27 [95% CI, 1.13-1.43], P<0.001), and lower risk of bleeding (adjusted HR, 0.86 [95% CI, 0.80-0.93], P<0.001) compared with warfarin.
Conclusions:
In patients with atrial fibrillation, DOACs are associated with similar mortality, lower bleeding, but higher stroke with bioprosthetic valve replacement and lower risk of all 3 outcomes with MV repair compared with warfarin.




J Am Heart Assoc: 24 Aug 2022:e026666; epub ahead of print
Mentias A, Saad M, Michael M, Nakhla S, ... Desai MY, Kapadia S
J Am Heart Assoc: 24 Aug 2022:e026666; epub ahead of print | PMID: 36000413
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Impact:
Abstract

Use and Out-of-Pocket Cost of Sacubitril-Valsartan in Patients With Heart Failure.

Shore S, Basu T, Kamdar N, Brady P, ... Chopra V, Nallamothu BK

Background:
Current guidelines recommend use of sacubitril-valsartan in patients with heart failure with reduced ejection fraction (HFrEF). Early data suggested low uptake of sacubitril-valsartan, but contemporary data on real-world use and their associated cost are limited. Methods and Results This was a retrospective study of individuals enrolled in Optum Clinformatics, a national insurance claims data set from 2016 to 2018. We included all adult patients with HFrEF with 2 outpatient encounters or 1 inpatient encounter with an International Classification of Diseases, Tenth Revision (ICD-10), diagnosis of HFrEF and 6 months of continuous enrollment, also receiving β-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers within 6 months of HFrEF diagnosis. We included 70 245 patients with HFrEF, and 5217 patients (7.4%) received sacubitril-valsartan prescriptions. Patients receiving care through a cardiologist compared with a primary care physician alone were more likely to receive sacubitril-valsartan (odds ratio, 1.61 [95% CI, 1.52-1.71]). Monthly out-of-pocket (OOP) cost for sacubitril-valsartan, compared with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, was higher for both commercially insured patients (mean, $69 versus $6.74) and Medicare Advantage (mean, $62 versus $2.52). For patients with commercial insurance, OOP cost was lower in 2016 than in 2018. For patients with Medicare Advantage, there was a significant geographic variation in the OOP costs across the country, ranging from $31 to $68 per month across different regions, holding all other patient-related factors constant.
Conclusions:
Sacubitril-valsartan use was infrequent among patients with HFrEF. Patients receiving care with a cardiologist were more likely to receive sacubitril-valsartan. OOP costs remain high, potentially limiting use. Significant geographic variation in OOP costs, unexplained by patient factors, was noted.




J Am Heart Assoc: 24 Aug 2022:e023950; epub ahead of print
Shore S, Basu T, Kamdar N, Brady P, ... Chopra V, Nallamothu BK
J Am Heart Assoc: 24 Aug 2022:e023950; epub ahead of print | PMID: 36000415
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Abstract

Coronary Artery Disease and Heart Failure With Preserved Ejection Fraction: The ARIC Study.

John JE, Claggett B, Skali H, Solomon SD, ... Chang PP, Shah AM

Background:
Whether coronary artery disease (CAD) is a significant risk factor for heart failure (HF) with preserved ejection fraction (HFpEF) is unclear. Methods and Results Among 9902 participants in the ARIC (Atherosclerosis Risk in Communities) study, we assessed the association of incident CAD with subsequent incident HFpEF (left ventricular ejection fraction [≥50%]) and HF with reduced ejection fraction (HFrEF; left ventricular ejection fraction <50%) using survival models with time-updated variables. We also assessed the extent to which echocardiographic correlates of prevalent CAD account for the relationship between CAD and incident HFpEF. Over 13-year follow-up, incident CAD developed in 892 participants and 178 subsequently developed HF (86 HFrEF, 71 HFpEF). Incident HFrEF and HFpEF risk were both greatest early after the CAD event. At >1 year post-CAD event, adjusted incidence of HFrEF and HFpEF were similar (7.2 [95% CI, 5.2-10.0] and 6.7 [4.8-9.2] per 1000 person-years, respectively) and CAD remained predictive of both (HFrEF: hazard ratio, 2.76 [95% CI, 1.99-3.84]; HFpEF: 1.85 [1.35-2.54]) after adjusting for demographics and common comorbidities. Among 4779 HF-free participants at Visit 5 (2011-2013), the 490 with prevalent CAD had lower left ventricular ejection fraction and higher left ventricular mass index, E/e\', and left atrial volume index (all P<0.01). The association of prevalent CAD with incident HFpEF post-Visit 5 was not significant after adjusting for echocardiographic measures, with the greatest attenuation observed for left ventricular diastolic function.
Conclusions:
CAD is a significant risk factor for incident HFpEF after adjustment for demographics and common comorbidities. This relationship is partially accounted for by echocardiographic alterations, particularly left ventricular diastolic function.




J Am Heart Assoc: 24 Aug 2022:e021660; epub ahead of print
John JE, Claggett B, Skali H, Solomon SD, ... Chang PP, Shah AM
J Am Heart Assoc: 24 Aug 2022:e021660; epub ahead of print | PMID: 36000416
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Impact:
Abstract

Characteristics, Predictors, and Outcomes of Early mTOR Inhibitor Use After Heart Transplantation: Insights From the UNOS Database.

Kampaktsis PN, Doulamis IP, Asleh R, Makri E, ... Duque ER, Briasoulis A

Background:
The clinical characteristics of mTOR (mammalian target of rapamycin) inhibitors use in heart transplant recipients and their outcomes have not been well described. Methods and Results We compared patients who received mTOR inhibitors within the first 2 years after heart transplantation to patients who did not by inquiring the United Network for Organ Sharing (UNOS) database between 2010 and 2018. The primary end point was all-cause mortality with retransplantation as a competing event. Rejection, malignancy, hospitalization for infection, and renal transplantation were secondary end points. There were 1619 (9%) and 15 686 (81%) mTOR inhibitors+ and mTOR inhibitors- patients, respectively. Body mass index, induction, cardiac allograft vasculopathy, calculated panel reactive antibody, and fewer days in 1A status were independently associated with mTOR inhibitors+ status. Over a follow-up of 10.4 years, there was no difference in all-cause mortality after adjusting for donor and recipient characteristics (adjusted subdistribution hazard ratio, 1.03 [0.90-1.19]; P=0.66). mTOR inhibitors+ were independently associated with increased risk for rejection (odds ratio [OR], 1.43 [1.11-1.83]; P=0.005) and basal skin cancer (OR, 1.35 [1.19-1.51]; P=0.012) but not for infection or renal transplantation.
Conclusions:
mTOR inhibitors are used in <10% patients in the first 2 years after heart transplantation and are noninferior to contemporary immunosuppression regimens in terms of all-cause mortality, infection, malignancy, or renal transplantation. They are associated with risk for rejection.




J Am Heart Assoc: 24 Aug 2022:e025507; epub ahead of print
Kampaktsis PN, Doulamis IP, Asleh R, Makri E, ... Duque ER, Briasoulis A
J Am Heart Assoc: 24 Aug 2022:e025507; epub ahead of print | PMID: 36000418
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Abstract

Outcomes of Patients Hospitalized With Cardiovascular Implantable Electronic Device-Related Infective Endocarditis, Prosthetic Valve Endocarditis, and Native Valve Endocarditis: A Nationwide Study, 2003 to 2017.

Khaloo P, Uzomah UA, Shaqdan A, Ledesma PA, ... Ptaszek LM, Ruskin JN

Background:
Most published reports describing outcomes of patients with cardiovascular implantable electronic device-related infective endocarditis (CIED-IE) are single-center studies with small patient sample sizes. The goal of this study was to utilize population-based data to assess trends in CIED-IE hospitalization and to compare outcomes between patients hospitalized with CIED-IE, prosthetic valve endocarditis (PVE), and native valve endocarditis (NVE). Methods and Results A query of the National (Nationwide) Inpatient Sample (NIS) database between 2003 and 2017 identified 646 325 patients hospitalized with infective endocarditis in the United States of whom 585 974 (90%) had NVE, 27 257 (4.2%) had CIED-IE, and 26 111 (4%) had PVE. There was a 509% increase in CIED-IE hospitalizations in the United States from 2003 to 2017 (P trend<0.001). In-hospital mortality and length of stay associated with CIED-IE decreased during the study period from 15% and 20 days in 2003 to 9.7% and 19 days in 2017 (P trend=0.032 and 0.018, respectively). The in-hospital mortality rate was lower in patients hospitalized with CIED-IE (9.2%) than in patients with PVE (12%) and NVE (12%). Length of stay was longest in the CIED-IE group (17 compared with 14 days for both NVE and PVE). Hospital costs were highest for the CIED-IE group ($56 000 compared with $37 000 in NVE and $45 000 in PVE).
Conclusions:
Despite the fact that the number of comorbidities per patient with CIED-IE increased during the study period, mortality rate and hospital length of stay decreased. The mortality rate was significantly lower for patients with CIED-IE than for patients with NVE and PVE. Patients with CIED-IE had the longest lengths of stay and highest hospital costs.




J Am Heart Assoc: 24 Aug 2022:e025600; epub ahead of print
Khaloo P, Uzomah UA, Shaqdan A, Ledesma PA, ... Ptaszek LM, Ruskin JN
J Am Heart Assoc: 24 Aug 2022:e025600; epub ahead of print | PMID: 36000421
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Abstract

Inflammatory Role of Milk Fat Globule-Epidermal Growth Factor VIII in Age-Associated Arterial Remodeling.

Ni L, Liu L, Zhu W, Telljohann R, ... Lakatta EG, Wang M

Background:
Age-associated aortic remodeling includes a marked increase in intimal medial thickness (IMT), associated with signs of inflammation. Although aortic wall milk fat globule-epidermal growth factor VIII (MFG-E8) increases with age, and is associated with aortic inflammation, it is not known whether MFG-E8 is required for the age-associated increase in aortic IMT. Here, we tested whether MFG-E8 is required for the age-associated increase in aortic IMT. Methods and Results To determine the role of MFG-E8 in the age-associated increase of IMT, we compared aortic remodeling in adult (20-week) and aged (96-week) MFG-E8 (-/-) knockout and age matched wild-type (WT) littermate mice. The average aortic IMT increased with age in the WT from 50±10 to 70±20 μm (P<0.0001) but did not significantly increase with age in MFG-E8 knockout mice. Because angiotensin II signaling is implicated as a driver of age-associated increase in IMT, we infused 30-week-old MFG-E8 knockout and age-matched littermate WT mice with angiotensin II or saline via osmotic mini-pumps to determine whether MFG-E8 is required for angiotensin II-induced aortic remodeling. (1) In WT mice, angiotensin II infusion substantially increased IMT, elastic lamina degradation, collagen deposition, and the proliferation of vascular smooth muscle cells; in contrast, these effects were significantly reduced in MFG-E8 KO mice; (2) On a molecular level, angiotensin II treatment significantly increased the activation and expression of matrix metalloproteinase type 2, transforming growth factor beta 1, and its downstream signaling molecule phosphorylated mother against decapentaplegic homolog 2, and collagen type I production in WT mice; however, in the MFG-E8 knockout mice, these molecular effects were significantly reduced; and (3) in WT mice, angiotensin II increased levels of aortic inflammatory markers phosphorylated nuclear factor-kappa beta p65, monocyte chemoattractant protein 1, tumor necrosis factor alpha, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 molecular expression, while in contrast, these inflammatory markers did not change in knockout mice.
Conclusions:
Thus, MFG-E8 is required for both age-associated proinflammatory aortic remodeling and also for the angiotensin II-dependent induction in younger mice of an aortic inflammatory phenotype observed in advanced age. Targeting MFG-E8 would be a novel molecular approach to curb adverse arterial remodeling.




J Am Heart Assoc: 24 Aug 2022:e022574; epub ahead of print
Ni L, Liu L, Zhu W, Telljohann R, ... Lakatta EG, Wang M
J Am Heart Assoc: 24 Aug 2022:e022574; epub ahead of print | PMID: 36000422
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Abstract

Gut Microbiota and Coronary Plaque Characteristics.

Nakajima A, Mitomo S, Yuki H, Araki M, ... Nakamura S, Jang IK

Background:
The relationship between gut microbiota and in vivo coronary plaque characteristics has not been reported. This study was conducted to investigate the relationship between gut microbiota and coronary plaque characteristics in patients with coronary artery disease. Methods and Results Patients who underwent both optical coherence tomography and intravascular ultrasound imaging and provided stool and blood specimens were included. The composition of gut microbiota was evaluated using 16S rRNA sequencing. A total of 55 patients were included. At the genus level, 2 bacteria were associated with the presence of thin-cap fibroatheroma, and 9 bacteria were associated with smaller fibrous cap thickness. Among them, some bacteria had significant associations with inflammatory/prothrombotic biomarkers. Dysgonomonas had a positive correlation with interleukin-6, Paraprevotella had a positive correlation with fibrinogen and negative correlation with high-density lipoprotein cholesterol, Succinatimonas had positive correlations with fibrinogen and homocysteine, and Bacillus had positive correlations with fibrinogen and high-sensitivity C-reactive protein. In addition, Paraprevotella, Succinatimonas, and Bacillus were also associated with greater plaque volume. Ten bacteria were associated with larger fibrous cap thickness. Some were associated with protective biomarker changes; Anaerostipes had negative correlations with trimethylamine N-oxide, tumor necrosis factor α, and interleukin-6, and Dielma had negative correlations with trimethylamine N-oxide, white blood cells, plasminogen activator inhibitor-1, and homocysteine, and a positive correlation with high-density lipoprotein cholesterol.
Conclusions:
Bacteria that were associated with vulnerable coronary plaque phenotype and greater plaque burden were identified. These bacteria were also associated with elevated inflammatory or prothrombotic biomarkers. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000041692.




J Am Heart Assoc: 24 Aug 2022:e026036; epub ahead of print
Nakajima A, Mitomo S, Yuki H, Araki M, ... Nakamura S, Jang IK
J Am Heart Assoc: 24 Aug 2022:e026036; epub ahead of print | PMID: 36000423
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Abstract

Renin-Angiotensin System Inhibitors in Patients With COVID-19: A Meta-Analysis of Randomized Controlled Trials Led by the International Society of Hypertension.

Gnanenthiran SR, Borghi C, Burger D, Caramelli B, ... Schutte AE, COVID‐METARASI Consortium

Background:
Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis to assess the safety and efficacy of RASi in adults with COVID-19. Methods and Results MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID-19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all-cause mortality at ≤30 days. A total of 14 randomized controlled trials met the inclusion criteria and enrolled 1838 participants (aged 59 years, 58% men, mean follow-up 26 days). Of the trials, 11 contributed data. We found no effect of RASi versus control on all-cause mortality (7.2% versus 7.5%; relative risk [RR], 0.95; [95% CI, 0.69-1.30]) either overall or in subgroups defined by COVID-19 severity or trial type. Network meta-analysis identified no difference between angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers. RASi users had a nonsignificant reduction in acute myocardial infarction (2.1% versus 3.6%; RR, 0.59; [95% CI, 0.33-1.06]), but increased risk of acute kidney injury (7.0% versus 3.6%; RR, 1.82; [95% CI, 1.05-3.16]), in trials that initiated and continued RASi. There was no increase in need for dialysis or differences in congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, or mechanical ventilation.
Conclusions:
This meta-analysis of randomized controlled trials evaluating angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers versus control in patients with COVID-19 found no difference in all-cause mortality, a borderline decrease in myocardial infarction, and an increased risk of acute kidney injury with RASi. Our findings provide strong evidence that RASi can be used safely in patients with COVID-19.




J Am Heart Assoc: 24 Aug 2022:e026143; epub ahead of print
Gnanenthiran SR, Borghi C, Burger D, Caramelli B, ... Schutte AE, COVID‐METARASI Consortium
J Am Heart Assoc: 24 Aug 2022:e026143; epub ahead of print | PMID: 36000426
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Abstract

Clinical Outcomes of Percutaneous Coronary Intervention for Bifurcation Lesions According to Medina Classification.

Mohamed MO, Lamellas P, Roguin A, Oemrawsingh RM, ... Mamas MA, e‐Ultimaster investigators

Background:
Coronary bifurcation lesions (CBLs) are frequently encountered in clinical practice and are associated with worse outcomes after percutaneous coronary intervention. However, there are limited data around the prognostic impact of different CBL distributions. Methods and Results All CBL percutaneous coronary intervention procedures from the prospective e-Ultimaster (Prospective, Single-Arm, Multi Centre Observations Ultimaster Des Registry) multicenter international registry were analyzed according to CBL distribution as defined by the Medina classification. Cox proportional hazards models were used to compare the hazard ratio (HR) of the primary outcome, 1-year target lesion failure (composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target lesion revascularization), and its individual components between Medina subtypes using Medina 1.0.0 as the reference category. A total of 4003 CBL procedures were included. The most prevalent Medina subtypes were 1.1.1 (35.5%) and 1.1.0 (26.8%), whereas the least prevalent was 0.0.1 (3.5%). Overall, there were no significant differences in patient and procedural characteristics among Medina subtypes. Only Medina 1.1.1 and 0.0.1 subtypes were associated with increased target lesion failure (HR, 2.6 [95% CI, 1.3-5.5] and HR, 4.0 [95% CI, 1.6-9.0], respectively) at 1 year, compared with Medina 1.0.0, prompted by clinically driven target lesion revascularization (HR, 3.1 [95% CI, 1.1-8.6] and HR, 4.6 [95% CI, 1.3-16.0], respectively) as well as cardiac death in Medina 0.0.1 (HR, 4.7 [95% CI, 1.0-21.6]). No differences in secondary outcomes were observed between Medina subtypes.
Conclusions:
In a large multicenter registry analysis of coronary bifurcation percutaneous coronary intervention procedures, we demonstrate prognostic differences in 1-year outcomes between different CBL distributions, with Medina 1.1.1 and 0.0.1 subtypes associated with an increased risk of target lesion failure.




J Am Heart Assoc: 24 Aug 2022:e025459; epub ahead of print
Mohamed MO, Lamellas P, Roguin A, Oemrawsingh RM, ... Mamas MA, e‐Ultimaster investigators
J Am Heart Assoc: 24 Aug 2022:e025459; epub ahead of print | PMID: 36000428
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Abstract

Association of In-Hospital Hemoglobin Drop With Decreased Myocardial Salvage and Increased Long-Term Mortality in Patients With Acute ST-Segment-Elevation Myocardial Infarction.

Dutsch A, Graesser C, Voll F, Novacek S, ... Kessler T, Sager HB

Background:
Anemia and blood loss occur often in patients with ST-segment-elevation myocardial infarction (STEMI). In-hospital hemoglobin drop is associated with 1-year mortality in patients with acute coronary syndrome. However, data on the effect of hemoglobin reduction on myocardial salvage and long-term outcomes are scarce. We investigated the impact of in-hospital hemoglobin drop on myocardial salvage and 5-year mortality in patients with STEMI treated with primary percutaneous coronary intervention. Methods and Results In-hospital hemoglobin drop was defined as a decrease in hemoglobin levels from admission and nadir hemoglobin values. Patients were categorized as having the following: no drop, minimal drop (<3 g/dL), minor drop (≥3 to <5 g/dL), and major drop (≥5 g/dL). Myocardial area at risk and infarct size were measured using serial single-photon emission computerized tomography imaging. The co-primary outcomes were myocardial salvage and 5-year all-cause mortality. Of 1204 patients, 1169 (97.1%) showed a hemoglobin drop during hospitalization: minimal, minor, and major drop occurred in 894 (74.3%), 214 (17.8%), and 61 (5.1%) patients, respectively. Myocardial salvage was reduced in patients with minimal (median, 0.53 [interquartile range, 0.27-0.83]), minor (median, 0.40 [interquartile range, 0.18-0.62]), and major (median, 0.40 [interquartile range, 0.14-0.77]) drop compared with patients without drop (median, 0.70 [interquartile range, 0.44-1.0], P<0.001). After adjusting for covariates, hemoglobin drop remained an independent correlate of poor myocardial salvage. A drop of ≥3 g/dL was associated with reduced left ventricular function at 6 months and with increased mortality at 5-year follow-up after STEMI.
Conclusions:
In patients with STEMI undergoing primary percutaneous coronary intervention, in-hospital hemoglobin drop was associated with reduced myocardial salvage, left ventricular function, and increased long-term mortality.




J Am Heart Assoc: 24 Aug 2022:e024857; epub ahead of print
Dutsch A, Graesser C, Voll F, Novacek S, ... Kessler T, Sager HB
J Am Heart Assoc: 24 Aug 2022:e024857; epub ahead of print | PMID: 36000430
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Abstract

Religiosity/Spirituality and Cardiovascular Health: The American Heart Association Life\'s Simple 7 in African Americans of the Jackson Heart Study.

Brewer LC, Bowie J, Slusser JP, Scott CG, ... Patten CA, Sims M

Background:
Religiosity/spirituality is a major coping mechanism for African Americans, but no prior studies have analyzed its association with the American Heart Association Life\'s Simple 7 (LS7) indicators in this group. Methods and Results This cross-sectional study using Jackson Heart Study (JHS) data examined relationships between religiosity (religious attendance, private prayer, religious coping) and spirituality (theistic, nontheistic, total) with LS7 individual components (eg, physical activity, diet, smoking, blood pressure) and composite score among African Americans. Multivariable logistic regression assessed the odds of achieving intermediate/ideal (versus poor) LS7 levels adjusted for sociodemographic, behavioral, and biomedical factors. Among the 2967 participants (mean [SD] age=54.0 [12.3] years; 65.7% women), higher religious attendance was associated with increased likelihood (reported as odds ratio [95% CI]) of achieving intermediate/ideal levels of physical activity (1.16 [1.06-1.26]), diet (1.10 [1.01-1.20]), smoking (1.50 [1.34-1.68]), blood pressure (1.12 [1.01-1.24]), and LS7 composite score (1.15 [1.06-1.26]). Private prayer was associated with increased odds of achieving intermediate/ideal levels for diet (1.12 [1.03-1.22]) and smoking (1.24 [1.12-1.39]). Religious coping was associated with increased odds of achieving intermediate/ideal levels of physical activity (1.18 [1.08-1.28]), diet (1.10 [1.01-1.20]), smoking (1.32 [1.18-1.48]), and LS7 composite score (1.14 [1.04-1.24]). Total spirituality was associated with increased odds of achieving intermediate/ideal levels of physical activity (1.11 [1.02-1.21]) and smoking (1.36 [1.21-1.53]).
Conclusions:
Higher levels of religiosity/spirituality were associated with intermediate/ideal cardiovascular health across multiple LS7 indicators. Reinforcement of religiosity/spirituality in lifestyle interventions may decrease overall cardiovascular disease risk among African Americans.




J Am Heart Assoc: 24 Aug 2022:e024974; epub ahead of print
Brewer LC, Bowie J, Slusser JP, Scott CG, ... Patten CA, Sims M
J Am Heart Assoc: 24 Aug 2022:e024974; epub ahead of print | PMID: 36000432
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