Journal: Am Heart J

Sorted by: date / impact
Abstract

Days alive out of hospital in heart failure: Insights from the PARADIGM-HF and CHARM trials.

Chen Y, Lawrence J, Stockbridge N
Background
An endpoint that has received some attention in recent cardiovascular trials is \'days alive and out of hospital\' (DAOH). Percent DAOH is a natural extension of DAOH that adjusts for differences in length of follow-up. This endpoint measure incorporates mortality and morbidity together in a way that has the potential to give more insight regarding treatment effects compared to conventional time-to-event endpoints. Other advantages of this measure include the relative ease of collection and interpretation. However, research on how to analyze this measure is still limited.
Methods
We propose using the one-inflated beta model to analyze percent DAOH. This model is appropriate for highly left-skewed data with a large proportion of boundary values. Data from the Prospective Comparison of ARNI [Angiotensin Receptor-Neprilysin Inhibitor] with ACEI [Angiotensin-Converting-Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF) and Candesartan in Heart Failure Assessment of Reduction in Mortality and morbidity (CHARM) trials are used to illustrate this method.
Results
Statistically significant differences in percent DAOH were observed for PARADIGM-HF and CHARM in favor of treatment. In PARADIGM-HF, treatment with sacubitril plus valsartan increased DAOH on average by 11 days (95% CI: 1.4-20.9 days) and increased percent DAOH by 1.64% at a fixed follow-up length of 1,000 days (95% CI: 0.61%- 2.67%). For the CHARM overall program, the candesartan group has 1.79% more DAOH (95% CI: 0.91%- 2.68%).
Conclusion
DAOH, and especially percent DAOH, can enhance our understanding of treatment effects in future cardiovascular trials, and the one-inflated beta model is an appropriate choice for its analysis.

Published by Elsevier Inc.

Am Heart J: 30 Oct 2021; 241:108-119
Chen Y, Lawrence J, Stockbridge N
Am Heart J: 30 Oct 2021; 241:108-119 | PMID: 33984319
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Abstract

Coarctation of aorta is associated with left ventricular stiffness, left atrial dysfunction and pulmonary hypertension.

Egbe AC, Miranda WR, Connolly HM, Borlaug BA
Background
Brachial systolic blood pressure (BP) is the most commonly used metric for monitoring hypertension. However, recent studies suggest that brachial systolic BP underestimates left ventricle (LV) systolic load in patients with coarctation of aorta (COA). Since brachial systolic BP is used as a surrogate of arterial afterload in clinical practice, it is important to determine how well it correlates with LV remodeling and stiffness in patients with COA as compared to patients with idiopathic hypertension.
Methods
This is cross-sectional study of COA patients with hypertension (COA group) and adults with idiopathic hypertension (control group). Both groups were matched 1:1 based on age, sex, BMI and systolic BP. We hypothesized that the COA group will have higher LV systolic and diastolic stiffness, and more advanced left atrial remodeling and pulmonary hypertension. We assessed LV systolic stiffness using end-systolic elastance, and diastolic stiffness using LV stiffness constant and chamber capacitance (LV-end-diastolic volume at an end-diastolic pressure of 20mm Hg)
Results:
There were 112 patients in each group. Although both groups had similar systolic BP, the COA group had a higher end-systolic elastance (2.37 ± 0.74 vs 2.11 ± 0.54 mm Hg/mL, P= .008), higher LV stiffness constant (6.91 ± 0.81 vs 5.93 ± 0.79, P= .006) and lower LV-end-diastolic volume at an end-diastolic pressure of 20mm Hg (58 ± 9 vs 67 ± 11 mL/m2, P< .001). Additionally, the COA group had more advanced left atrial remodeling and higher pulmonary artery pressures which is corroborating evidence of high LV filling pressure.
Conclusions
COA patients have more LV stiffness and abnormal hemodynamics compared to non-COA patients with similar systolic BP, suggesting that systolic BP may underestimate LV systolic load in this population. Further studies are required to determine whether the observed LV stiffness and dysfunction translates to more cardiovascular events during follow-up, and whether adopting a stricter systolic BP target in clinical practice or changing threshold for COA intervention will lead to less LV stiffness and better clinical outcomes.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Oct 2021; 241:50-58
Egbe AC, Miranda WR, Connolly HM, Borlaug BA
Am Heart J: 30 Oct 2021; 241:50-58 | PMID: 34289342
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Abstract

Epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (The EXACT Trial): Rationale, design, and clinical considerations.

Povsic TJ, Henry TD, Ohman EM, Pepine CJ, ... Answini GA, Mokadam NA
Background
Patients with refractory angina (RA) have poor quality of life and new therapies are needed. XC001 is a novel adenoviral vector expressing multiple isoforms of vascular endothelial growth factor (VEGF) promoting an enhanced local angiogenic effect.
Methods
The Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) trial is a 6-month (with 6-month extension) phase 1/2, first-in-human, multicenter, open-label, single-arm, dose-escalation study to evaluate the safety, tolerability, and preliminary efficacy of XC001 in patients with RA. The trial will enroll 33 patients in an initial (n = 12) ascending dose-escalation phase (1 × 109, 1 × 1010, 4 × 1010, and 1 × 1011 viral particles), followed by phase 2 (n = 21) assessing the highest tolerated dose. Patients must have stable Canadian Cardiovascular Society (CCS) class II-IV angina on maximally tolerated medical therapy without options for conventional revascularization, demonstrable ischemia on stress testing, and angina limiting exercise tolerance. XC001 will be delivered directly to ischemic myocardium via surgical transthoracic epicardial access. The primary outcome is safety via adverse event monitoring through 6 months. Efficacy assessments include difference from baseline to month 6 in time to 1 mm of ST segment depression, time to angina, and total exercise duration; myocardial blood flow at rest, and stress and coronary flow reserve by positron emission tomography; quality of life; CCS functional class; and angina frequency.
Conclusions
The EXACT trial will determine whether direct intramyocardial administration of XC001 in patients with RA is safe and evaluate its effect on exercise tolerance, myocardial perfusion, angina and physical activity, informing future clinical investigation.
Clinical trial registration
NCT04125732.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Oct 2021; 241:38-49
Povsic TJ, Henry TD, Ohman EM, Pepine CJ, ... Answini GA, Mokadam NA
Am Heart J: 30 Oct 2021; 241:38-49 | PMID: 34224684
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Abstract

Impact of oral soluble guanylate cyclase stimulators in heart failure: A systematic review and Meta-analysis of randomized controlled trials.

Moghaddam N, Malhi N, Toma M
Background
Soluble guanylate cyclase (sGC) stimulators are a novel class of medications with emerging role in heart failure (HF). The aim of this study is to evaluate the efficacy and safety of oral sGC stimulators in patients with HF with reduced and preserved ejection fraction (HFrEF and HFpEF) by pooling data from all available randomized control trials (RCT).
Methods
A comprehensive search of electronic databases from 2000-2020 was performed. Seven RCTs, three HFrEF and four HFpEF studies, were identified. The follow-up duration ranged from 1 month to a median of 10.8 months. A random-effects meta-analysis was conducted to summarize the studies.
Results
The study population included 7190 patients: 5707 HFrEF and 1483 HFpEF patients. In HFrEF, oral sGC stimulators reduced the composite incidence of HF hospitalization and cardiovascular death (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78-0.97; I2 = 0%), primarily driven by lower HF hospitalization (HR 0.88, 95% CI 0.78-0.99; I2 = 0%). There was no significant reduction in all-cause death in HFrEF (HR 0.95, 95% CI 0.83-1.09; I2 = 0%). In HFpEF, there were no improvements in Kansas City Cardiomyopathy Questionnaire clinical summary scores (mean difference 0.81, 95% CI -2.16-3.77; I2 = 72%) or 6-minute walk distance (mean difference 3.34 meters, 95% CI -7.86-14.54; I2 = 28%). There was no difference in all-cause mortality in HFpEF (HR 1.94, 95% CI 0.92-4.09; I2 = 0%). Overall, oral sGC stimulators had low medication-related serious adverse events.
Conclusion
Oral sGC stimulators are well tolerated in HF and reduce the incidence of HF hospitalization but not cardiovascular death among patients with HFrEF. However, there are no apparent benefits in HFpEF.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Oct 2021; 241:74-82
Moghaddam N, Malhi N, Toma M
Am Heart J: 30 Oct 2021; 241:74-82 | PMID: 34283990
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Abstract

Atrial function in paroxysmal AF patients with and without heart failure with preserved ejection fraction: data from the AF-RISK study.

Arita VA, Santema BT, De With RR, Nguyen BO, ... Voors AA, Rienstra M
Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are two cardiovascular conditions that often coexist. Strain phases of both the left and right atria are more impaired in paroxysmal AF patients with HFpEF than those without HFpEF in spite of comparable global longitudinal strain of the left ventricle. Atrial function may differentiate paroxysmal AF patients with HFpEF from those without HFpEF.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 20 Oct 2021; epub ahead of print
Arita VA, Santema BT, De With RR, Nguyen BO, ... Voors AA, Rienstra M
Am Heart J: 20 Oct 2021; epub ahead of print | PMID: 34688651
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Abstract

Real-World Antithrombotic Treatment Variability in Patients Undergoing Peripheral Vascular Intervention: Insights from the VQI Registry.

Lee M, Ahmed ZV, Huang J, Jelani QU, ... Smolderen KG, Mena-Hurtado C
For those undergoing peripheral vascular interventions (PVI), guidelines indicate the use of dual antiplatelet therapy (DAPT) is reasonable (Class IIb), but recommendations have not reached the highest level of evidence. In the largest effort to date, we found that antithrombotic prescription was dominated by single antiplatelet therapy (SAPT) (51.4%) before PVI, which switched to DAPT (57.7%) following PVI, with some patients still remaining on no therapy (8%). High site variability in prescription rates (median odds ratio: 1.40, 95% confidence interval: 1.32, 1.48) was not much explained by patient and provider factors, revealing a need for the creation and integration of the newest trial data and for interventions at the health system or practice level to help physicians determine the optimal medical therapy following PVI.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 20 Oct 2021; epub ahead of print
Lee M, Ahmed ZV, Huang J, Jelani QU, ... Smolderen KG, Mena-Hurtado C
Am Heart J: 20 Oct 2021; epub ahead of print | PMID: 34688650
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Abstract

Cardiovascular risk factor profiles in North and South Indian and Pakistani Americans: The MASALA Study.

Reddy NK, Kaushal V, Kanaya AM, Kandula NR, Gujral UP, Shah NS
South Asians in the United States have disproportionately high burden of cardiovascular disease compared to other race/ethnic groups but are a heterogenous population, so we evaluated differences in prevalence and adjusted odds of cardiovascular risk factors including diabetes, hypertension, dyslipidemia, and obesity between North Indian, South Indian, and Pakistani immigrants in the United States in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study. Given cultural differences among residents of Indian regions, for example in dietary patterns, we categorized Indian participants as North or South Indian. In 1,018 participants (728 North Indian [47% women], 223 South Indian [43% women], 67 Pakistani [52% women]), unadjusted diabetes and obesity prevalence was highest in Pakistani participants (33% and 48%, respectively); hypertension prevalence was highest in North Indian participants (54%); dyslipidemia prevalence was highest in South Indian and Pakistani participants (55%); and South Indian participants had a higher odds of dyslipidemia (OR 1.77, 95% CI 1.27, 2.47) compared with North Indian participants in fully adjusted models. As differences in cardiovascular risk factors were observed across South Asian American subgroups, identifying the determinants of suboptimal cardiovascular health within South Asian American subgroups may help to better tailor cardiovascular disease prevention strategies.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 20 Oct 2021; epub ahead of print
Reddy NK, Kaushal V, Kanaya AM, Kandula NR, Gujral UP, Shah NS
Am Heart J: 20 Oct 2021; epub ahead of print | PMID: 34688649
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Abstract

Design and Rationale of a Phase 2 Study of NeurOtoxin (Botulinum Toxin Type A) for the PreVention of Post-Operative Atrial Fibrillation - The NOVA Study.

Piccini JP, Ahlsson A, Dorian P, Gillinov MA, ... Ferguson WG, Benussi S
Background
Post-operative AF (POAF) is the most common complication following cardiac surgery, occurring in 30% to 60% of patients undergoing bypass and/or valve surgery. POAF is associated with longer intensive care unit/hospital stays, increased healthcare utilization, and increased morbidity and mortality. Injection of botulinum toxin type A into the epicardial fat pads resulted in reduction of AF in animal models, and in 2 clinical studies of cardiac surgery patients, without new safety observations.
Methods
The objective of NOVA is to assess the use of AGN-151607 (botulinum toxin type A) for prevention of POAF in cardiac surgery patients. This randomized, multi-site, placebo-controlled trial will study one-time injections of AGN-151607 125 U (25 U / fat pad) and 250 U (50 U / fat pad) or placebo during cardiac surgery in ∼330 participants. Primary endpoint: % of patients with continuous AF ≥ 30 s. Secondary endpoints include several measures of AF frequency, duration, and burden. Additional endpoints include clinically important tachycardia during AF, time to AF termination, and healthcare utilization. Primary and secondary efficacy endpoints will be assessed using continuous ECG monitoring for 30 days following surgery. All patients will be followed for up to 1 year for safety.
Conclusion
The NOVA Study will test the hypothesis that injections of AGN-151607 will reduce the incidence of POAF and associated resource utilization. If demonstrated to be safe and effective, the availability of a one-time therapy for the prevention of POAF would represent an important treatment option for patients undergoing cardiac surgery.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 19 Oct 2021; epub ahead of print
Piccini JP, Ahlsson A, Dorian P, Gillinov MA, ... Ferguson WG, Benussi S
Am Heart J: 19 Oct 2021; epub ahead of print | PMID: 34687654
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Abstract

Whole genome sequencing in transposition of the great arteries and associations with clinically relevant heart, brain and laterality genes.: WGS in transposition of the great arteries.

Blue GM, Mekel M, Das D, Troup M, ... Dunwoodie SL, Winlaw DS
Background
The most common cyanotic congenital heart disease (CHD) requiring management as a neonate is transposition of great arteries (TGA). Clinically, up to 50% of TGA patients develop some form of neurodevelopmental disability (NDD), thought to have a significant genetic component. A \'ciliopathy\' and links with laterality disorders have been proposed. This first report of whole genome sequencing (WGS) in TGA, sought to identify clinically relevant variants contributing to heart, brain and laterality defects.
Method
Initial WGS analyses on 100 TGA patients focussed on established disease genes related to CHD (n=107), NDD (n=659) and heterotaxy (n=74). Single variant as well as copy number variant analyses were conducted. Variant pathogenicity was assessed using the American College of Medical Genetics and Genomics-Association for Molecular Pathology guidelines.
Results
Fifty-five putatively damaging variants were identified in established disease genes associated with CHD, NDD and heterotaxy; however, no clinically relevant variants could be attributed to disease. Notably, case-control analyses identified significantly more predicted-damaging, silent and total variants in TGA cases than healthy controls in established CHD genes (p<0.001), NDD genes (p<0.001) as well as across the three gene panels (p<0.001).
Conclusion
We present compelling evidence that the majority of TGA is not caused by monogenic rare variants and is most likely oligogenic and/or polygenic in nature, highlighting the complex genetic architecture and multifactorial influences on this CHD sub-type and its long-term sequelae. Assessment of variant burden in key heart, brain and/or laterality genes may be required to unravel the genetic contributions to TGA and related disabilities.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 16 Oct 2021; epub ahead of print
Blue GM, Mekel M, Das D, Troup M, ... Dunwoodie SL, Winlaw DS
Am Heart J: 16 Oct 2021; epub ahead of print | PMID: 34670123
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Abstract

Distal versus conventional radial access for coronary angiography and intervention: design and rationale of DISCO RADIAL Study.

Aminian A, Sgueglia GA, Wiemer M, Gasparini GL, ... Borovicanin V, Saito S
Background
Transradial access (TRA) has become the default access method for coronary diagnostic and interventional procedures. As compared to transfemoral access, TRA has been shown to be safer, cost-effective and more patient-friendly. Radial artery occlusion (RAO) represents the most frequent complication of TRA, and precludes future coronary procedures through the radial artery, the use of the radial artery as a conduit for coronary artery bypass grafting or as arteriovenous fistula for patients on hemodialysis. Recently, distal radial access (DRA) has emerged as a promising alternative to TRA, yielding potential for minimizing the risk of RAO. However, an international multicenter randomized comparison between DRA and conventional TRA with respect to the rate of RAO is still lacking.
Trial design
DISCO RADIAL is a prospective, multicenter, open-label, randomized, controlled, superiority trial. A total of 1300 eligible patients will be randomly allocated to undergo coronary angiography and/or percutaneous coronary intervention (PCI) through DRA or TRA using the 6 Fr Glidesheath Slender sheath introducer. Extended experience with both TRA and DRA is required for operators\' eligibility and optimal evidence-based best practice to reduce RAO systematically implemented by protocol. The primary endpoint is the incidence of forearm RAO assessed by vascular ultrasound at discharge. Several important secondary endpoints will also be assessed, including access-site cross-over, hemostasis time and access-site related complications.
Summary
The DISCO RADIAL trial will provide the first large-scale multicenter randomized evidence comparing DRA to TRA in patients scheduled for coronary angiography or PCI with respect to the incidence of RAO at discharge.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 15 Oct 2021; epub ahead of print
Aminian A, Sgueglia GA, Wiemer M, Gasparini GL, ... Borovicanin V, Saito S
Am Heart J: 15 Oct 2021; epub ahead of print | PMID: 34666014
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Abstract

Incidence Rates and Predictors of Microvascular and Macrovascular Complications in Patients with Type 2 Diabetes: Results from the Longitudinal Global DISCOVER Study.

Arnold SV, Khunti K, Tang F, Chen H, ... Kosiborod M, On Behalf Of The Discover Investigators
Background
Micro- and macrovascular complications are a major cause of morbidity and mortality in people with type 2 diabetes (T2D). We sought to understand the global incidence rates and predictors of these complications.
Methods
We examined the incidence of vascular complications over 3 years of follow-up in the DISCOVER study-a global, observational study of people with T2D initiating second-line glucose-lowering therapy. Hierarchical Cox proportional hazards regression models examined factors associated with development of micro- and macrovascular complications during follow-up.
Results
Among 11,357 people with T2D from 33 countries (mean age 56.9 ± 11.7 years, T2D duration 5.7 ± 5.1 years, HbA1c 8.4 ± 1.7%), 19.0% had a microvascular complication at enrolment (most commonly neuropathy), and 13.2% had a macrovascular complication (most commonly coronary disease). Over 3 years of follow-up, 16.0% developed an incident microvascular complication, and 6.6% had an incident macrovascular complication. At the end of 3 years of follow-up, 31.5% of patients had at least one microvascular complication, and 16.6% had at least one macrovascular complication. Higher HbA1c and smoking were associated with greater risk of both incident micro- and macrovascular complications. Known macrovascular complications at baseline was the strongest predictor for development of new microvascular complications (HR 1.40, 95% CI 1.21-1.61) and new macrovascular complications (HR 3.39, 95% CI 2.84-4.06).
Conclusion
In this global study, both the prevalence and 3-year incidence of vascular complications were high in patients with relatively short T2D duration, highlighting the need for early risk-factor modification.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 15 Oct 2021; epub ahead of print
Arnold SV, Khunti K, Tang F, Chen H, ... Kosiborod M, On Behalf Of The Discover Investigators
Am Heart J: 15 Oct 2021; epub ahead of print | PMID: 34666013
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Abstract

Electrical cardioversion of atrial fibrillation and the risk of brady-arrhythmic events: Rasmussen et al: Electrical cardioversion and bradycardia.

Rasmussen PV, Blanche P, Dalgaard F, Gislason GH, ... Pallisgaard JL, Hansen ML
Background
Electrical cardioversion (ECV) is a common procedure for terminating atrial fibrillation (AF). ECV is associated with brady-arrhythmic events, however, the age-specific risks of clinically significant brady-arrhythmic events are unknown.
Methods
Using Danish nationwide registers, we identified patients with AF at their first non-emergent ECV between 2005 and 2018 and estimated their 30-day risk of brady-arrhythmic events. Moreover, factors associated with increased risks of brady-arrhythmias were identified. Absolute risks were estimated using logistic regression models fitted with natural splines as well as standardization (G-formula).
Results
We identified 20,725 eligible patients with a median age of 66 years (IQR 60-72) and most males (73%). The 30-day risks of brady-arrhythmic events after ECV were highly dependent on age with estimated risks ranging from 0.5 % (95% CI 0.2-1.7) and 1.2 % (95% CI 0.99-1.5) to 2.7 % (95% CI 2.1-3.3), and 5.1 % (95% 2.6-9.7) in patients aged 40, 65, 80, and 90 years, respectively. Factors associated with brady-arrhythmias were generally related to cardiovascular disease (e.g. ischemic heart disease, heart failure, valvular AF) or a history of syncope. We found no indications that pre-treatment with AADs conferred increased risks of brady-arrhythmic events (standardized absolute risk difference -0.25 % [95% CI -0.67 - 0.17]).
Conclusions
ECV conferred clinically relevant 30-day risks of brady-arrhythmic events, especially in older patients. AAD treatment was not found to increase the risk of brady-arrhythmias. Given the widespread use of ECV, these data should provide insights regarding the potential risks of brady-arrhythmic events.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 15 Oct 2021; epub ahead of print
Rasmussen PV, Blanche P, Dalgaard F, Gislason GH, ... Pallisgaard JL, Hansen ML
Am Heart J: 15 Oct 2021; epub ahead of print | PMID: 34666012
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Abstract

Factors Associated with Antihypertensive Monotherapy Among US Adults with Treated Hypertension and Uncontrolled Blood Pressure Overall and by Race/Ethnicity, NHANES 2013-2018.

Zheutlin AR, Derington CG, King JB, Berchie RO, ... Moran AE, Bress AP
Background
Treating hypertension with antihypertensive medications combinations, rather than one medication (i.e., monotherapy), is underused in the United States (US), particularly in certain race/ethnic groups. Identifying factors associated with monotherapy use despite uncontrolled blood pressure (BP) overall and within race/ethnic groups may elucidate intervention targets in under-treated populations.
Methods
Cross-sectional analysis of National Health and Nutrition Examination Surveys (NHANES; 2013-2014 through 2017-2018). We included participants age ≥20 years with hypertension, taking at least one antihypertensive medication, and uncontrolled BP (systolic BP [SBP] ≥140 mm Hg or diastolic BP [DBP] ≥90 mm Hg). Demographic, clinical, and healthcare-access factors associated with antihypertensive monotherapy were determined using multivariable-adjusted Poisson regression.
Results
Among 1,597 participants with hypertension and uncontrolled BP, age- and sex- adjusted prevalence of monotherapy was 42.6% overall, 45.4% among non-Hispanic White, 31.9% among non-Hispanic Black, 39.6% among Hispanic, and 50.9% among non-Hispanic Asian adults. Overall, higher SBP was associated with higher monotherapy use, while older age, having a healthcare visit in the previous year, higher BMI, and having heart failure were associated with lower monotherapy use.
Conclusion
Clinical and healthcare-access factors, including a healthcare visit within the previous year and co-morbid conditions were associated with a higher likelihood of combination antihypertensive therapy.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 14 Oct 2021; epub ahead of print
Zheutlin AR, Derington CG, King JB, Berchie RO, ... Moran AE, Bress AP
Am Heart J: 14 Oct 2021; epub ahead of print | PMID: 34662571
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Abstract

Catheter Ablation for Persistent Atrial Fibrillation: a Multicentre Randomised Trial of Pulmonary Vein Isolation (PVI) versus PVI with Posterior Left Atrial Wall Isolation (PWI) - the CAPLA Study: CAPLA: randomised trial for persistent AF.

Chieng D, Sugumar H, Ling LH, Segan L, ... Kalman JM, Kistler PM
Background
The success of pulmonary vein isolation (PVI) is reduced in persistent AF (PsAF) compared to paroxysmal AF. Adjunctive ablation strategies have failed to show consistent incremental benefit over PVI alone in randomised studies. The left atrial posterior wall is a potential source of non-PV triggers and atrial substrate which may promote the initiation and maintenance of PsAF. Adding posterior wall isolation (PWI) to PVI had shown conflicting outcomes, with earlier studies confounded by methodological limitations.
Objectives
To determine whether combining PWI with PVI significantly improves freedom from AF recurrence, compared to PVI alone, in patients with PsAF.
Methods
This is a multi-centre, prospective, international randomised clinical trial. 338 patients with symptomatic PsAF refractory to anti-arrhythmic therapy (AAD) will be randomised to either PVI alone or PVI with PWI in a 1:1 ratio. PVI involves wide antral circumferential pulmonary vein (PV) isolation, utilising contact force sensing ablation catheters. PWI involves the creation of a floor line connecting the inferior aspect of the PVs, and a roof line connecting the superior aspect of the PVs. Follow up is for a minimum of 12 months with rhythm monitoring via implantable cardiac device/ loop monitor, or frequent intermittent monitoring with an ECG device. The primary outcome is freedom from any documented atrial arrhythmia of > 30 seconds off AAD at 12 months, after a single ablation procedure.
Conclusion
This randomised study aims to determine the success and safety of adjunctive PWI to PVI in patients with persistent AF.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 03 Oct 2021; epub ahead of print
Chieng D, Sugumar H, Ling LH, Segan L, ... Kalman JM, Kistler PM
Am Heart J: 03 Oct 2021; epub ahead of print | PMID: 34619143
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Abstract

Associations between neighborhood socioeconomic cluster and hypertension, diabetes, myocardial infarction, and coronary artery disease within a cohort of cardiac catheterization patients.

Weaver AM, McGuinn LA, Neas L, Devlin RB, ... Hauser ER, Diaz-Sanchez D
Background
Neighborhood-level socioeconomic status (SES) is associated with health outcomes, including cardiovascular disease (CVD) and diabetes, but these associations are rarely studied across large, diverse populations.
Methods
We used Ward\'s Hierarchical clustering to define eight neighborhood clusters across North Carolina (NC) using 11 census-based indicators of SES, race, housing, and urbanicity and assigned 6992 cardiac catheterization patients at Duke University Hospital from 2001-2010 to clusters. We examined associations between clusters and coronary artery disease index > 23 (CAD), history of myocardial infarction (MI), hypertension, and diabetes using logistic regression adjusted for age, race, sex, body mass index, region of NC, distance to Duke University Hospital, and smoking status.
Results
Four clusters were urban, three rural, and one suburban higher-middle-SES (referent). We observed greater odds of MI in all six clusters with lower or middle-SES. Odds of CAD were elevated in the rural cluster that was low-SES and plurality Black (OR 1.16, 95% CI 0.94-1.43) and in the rural cluster that was majority American Indian (OR 1.31, 95% CI 0.91-1.90). Odds of diabetes and hypertension were elevated in two urban and one rural low- and lower-middle SES clusters with large Black populations.
Conclusions
We observed higher prevalence of CVD and diabetes in neighborhoods that were predominantly rural, low-SES, and non-White, highlighting the importance of public health and healthcare system outreach into these communities to promote cardiometabolic health and prevent and manage hypertension, diabetes and coronary artery disease.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 01 Oct 2021; epub ahead of print
Weaver AM, McGuinn LA, Neas L, Devlin RB, ... Hauser ER, Diaz-Sanchez D
Am Heart J: 01 Oct 2021; epub ahead of print | PMID: 34610283
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Impact:
Abstract

Stopping renin-angiotensin system inhibitors after hyperkalemia and risk of adverse outcomes.

Xu Y, Fu EL, Trevisan M, Jernberg T, ... Clase CM, Carrero JJ
Background
Stopping renin-angiotensin system inhibitors (RASi) after an episode of hyperkalemia is common but may involve therapeutic compromises, in that the cessation of RASi deprives patients of their beneficial cardiovascular effects.
Methods and results
Observational study from the Stockholm Creatinine Measurements (SCREAM) project including patients initiating RASi in routine care and surviving a first-detected episode of hyperkalemia (potassium >5.0 mmol/L). We used target trial emulation techniques based on cloning, censoring and weighting to compare stopping vs. continuing RASi within 6 months after hyperkalemia. Outcomes were 3-year risks of mortality, major adverse cardiovascular events (MACE, composite of cardiovascular death, myocardial infarction and stroke hospitalization) and recurrent hyperkalemia. Of 5669 new users of RASi who developed hyperkalemia (median age 72 years, 44% women), 1425 (25%) stopped RASi therapy within 6 months. Compared with continuing RASi, stopping therapy was associated with a higher 3-year risk of death (absolute risk difference 10.8%; HR 1.49, 95% CI 1.34-1.64) and MACE (risk difference 4.7%; HR 1.29, 1.14-1.45), but a lower risk of recurrent hyperkalemia (risk difference -9.5%; HR 0.76, 0.69-0.84). Results were consistent for events following potassium of >5.0 or >5.5 mmol/L, after censoring when the treatment decision was changed, across prespecified subgroups, and after adjusting for albuminuria.
Conclusion
These findings suggest that stopping RASi after hyperkalemia may be associated with a lower risk of recurrence of hyperkalemia, but higher risk of death and cardiovascular events.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 01 Oct 2021; epub ahead of print
Xu Y, Fu EL, Trevisan M, Jernberg T, ... Clase CM, Carrero JJ
Am Heart J: 01 Oct 2021; epub ahead of print | PMID: 34610282
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Impact:
Abstract

Effect of once-weekly exenatide on hospitalization for acute coronary syndrome or coronary revascularization in patients with type 2 diabetes mellitus.

Barbery CE, Giczewska A, White J, Lokhnygina Y, ... Hernandez AF, Jones WS
Cardiovascular (CV) outcome studies of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shifted the paradigm of type 2 diabetes management given their benefits regarding a reduction in major adverse CV events. However, the relationship between GLP-1 RAs and coronary revascularization remains poorly understood. In this EXSCEL post-hoc analysis, we used univariate Cox proportional models and Kaplan Meier survival analysis to evaluate the effect of once-weekly exenatide (EQW) on a composite outcome of hospitalization for acute coronary syndrome (ACS) or coronary revascularization. Similar models were utilized to evaluate the relationship between significant participant characteristics within the entire study population and the composite outcome. Of the 14,736 participants in EXSCEL with complete follow-up data, 1642 (11.1%) experienced an ACS or coronary revascularization event during a median follow-up of 3.3 years (interquartile range, 2.3-4.4). EQW had no effect on hospitalization for ACS or coronary revascularization (HR 1.00, 95% CI 0.91-1.10). Among EXSCEL participants, enrollment in Latin America (HR 0.51, 95% CI 0.43-0.60) and a history of peripheral artery disease (HR 0.79, 95% CI 0.70-0.90) were associated with a reduced risk for coronary revascularization, whereas enrollment in North America (HR 1.92, 95% CI 1.74-2.12), a history of CV disease (HR 3.24, 95% CI 2.78-3.78), and a previous myocardial infarction (HR 1.54, 95% CI 1.39-1.71) were associated with increased risk for study end points. EQW had no association with hospitalization for ACS or coronary revascularization. Participant enrollment location and CV disease burden may play a role in the variable CV efficacy of GLP-1 RAs that has been observed in trials thus far.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Sep 2021; 239:59-63
Barbery CE, Giczewska A, White J, Lokhnygina Y, ... Hernandez AF, Jones WS
Am Heart J: 29 Sep 2021; 239:59-63 | PMID: 33905751
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Impact:
Abstract

Rationale and design of the comparison of outcomes and access to care for heart failure (COACH) trial: A stepped wedge cluster randomized trial.

Lee DS, Straus SE, Austin PC, Mohamed S, ... Mak S, Ross HJ
Background
Heart failure (HF) is an ambulatory care sensitive condition and a leading reason for emergency department (ED) visits and hospitalizations. Improved decision-making and care may enhance safety and efficiency for patients presenting to the ED with acute HF.
Objectives
We will evaluate an intervention comprised of 2 complementary components: (1) the Emergency Heart Failure Mortality Risk Grade simultaneous 7- and 30-day (EHMRG30-ST) risk scores, which will inform admission-discharge decisions, and (2) a rapid outpatient follow-up (RAPID-HF) clinic for low-to-intermediate risk patients on cardiovascular readmissions or death.
Study design
Stepped wedge cluster randomized trial with cross-sectional measurement at 10 acute care hospitals in Ontario, Canada. Patients presenting during control and intervention periods are eligible if they have a primary ED diagnosis of HF. In the intervention periods, access to the EHMRG30-ST web calculator will become available to hospitals\' internet protocol (IP) addresses, and referral to the RAPID-HF clinic will be facilitated by a study nurse navigator. Patients with a high risk EHMRG30-ST score will be admitted to hospital. The RAPID-HF clinic will accept referrals for patients: (1) with low risk 7- and 30-day EHMRG30-ST scores who are discharged directly from the ED, or (2) intermediate risk patients with hospital length of stay < 72 hours. The RAPID-HF clinic, staffed by a nurse-clinician and cardiologist, will provide care during the 30-day transition after hospital separation.
Conclusion
This trial will determine whether novel risk stratification coupled with rapid ambulatory care achieves better outcomes than conventional decision-making and care for patients with HF.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 29 Sep 2021; 240:1-10
Lee DS, Straus SE, Austin PC, Mohamed S, ... Mak S, Ross HJ
Am Heart J: 29 Sep 2021; 240:1-10 | PMID: 33984316
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Impact:
Abstract

Computerized technologies informing cardiac catheterization and guiding coronary intervention.

Bajaj R, Parasa R, Ramasamy A, Makariou N, ... Baumbach A, Bourantas CV
Advances in image processing and computer hardware have enabled the development of user-friendly software which operate in real-time and can be used in the catheterization laboratory to facilitate percutaneous coronary intervention (PCI). The two dimensional-(2D) quantitative coronary angiography (QCA) systems that have traditionally been used to assess lesion severity have been replaced by 3D-QCA systems, enabling more reliable evaluation of vessel geometry and lesion dimensions. This also allows 3D reconstruction of coronary bifurcation anatomy and generation of models that can be processed by computational fluid dynamic techniques to reliably detect flow-limiting lesions. More recently, software has been introduced that has the capability of generating a digital silhouette of the coronary arteries superimposed onto X-ray angiography to facilitate wire crossing and stent placement, and potentially reduce contrast use. In parallel, methodologies have been developed that operate with an accessible interface and can process intravascular imaging data, reliably quantify lesion severity and co-register intravascular and X-ray angiographic data to comprehensively assess plaque distribution and guide PCI. The above advances are used in daily practice to improve procedural results and outcomes. This review aims to provide an overview of the developments in the field - it presents the computer-based technologies that have been designed to accurately assess lesion severity, summarizes the advantages and limitations of the systems introduced to co-register imaging data and discusses the potential value of the existing and emerging software in the catheterization laboratory.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 29 Sep 2021; 240:28-45
Bajaj R, Parasa R, Ramasamy A, Makariou N, ... Baumbach A, Bourantas CV
Am Heart J: 29 Sep 2021; 240:28-45 | PMID: 34077744
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Impact:
Abstract

Influenza Vaccination Among Adults with Cardiovascular Disease in the United States: Results from the Behavioral Risk Factor Surveillance System 2018-2019.

Pankayatselvan V, Mukamal KJ
Influenza causes significant morbidity and mortality among adults with cardiovascular disease (CVD). In nationally representative surveys of 101,210 individuals with CVD conducted in 2018 and 2019, the self-reported rate of vaccination was only 50%, with significant disparities by race and education. We advocate that cardiologists not only routinely emphasize vaccination but capitalize on the opportunity to vaccinate patients at office visits to improve overall rates of vaccination and their associated racial disparities.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 28 Sep 2021; epub ahead of print
Pankayatselvan V, Mukamal KJ
Am Heart J: 28 Sep 2021; epub ahead of print | PMID: 34599883
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Impact:
Abstract

Rationale and Design of the Small Annuli Randomized to Evolut or SAPIEN Trial (SMART Trial).

Herrmann HC, Abdel-Wahab M, Attizzani GF, Batchelor W, ... Mehran R, Tchetche D
Background
The SMall Annuli Randomized To Evolut or SAPIEN (SMART) Trial was designed to compare the performance of the two most widely available commercial transcatheter aortic valve replacement (TAVR) devices in patients with symptomatic severe native aortic stenosis with a small aortic valve annulus undergoing transfemoral TAVR. Patients with small aortic valve annuli are typically female and are often underrepresented in clinical trials.
Methods
The SMART Trial is an international, prospective, multi-center, randomized controlled, post-market trial. The trial will be conducted in approximately 700 subjects at approximately 90 sites globally. Inclusion criteria include severe aortic stenosis, aortic valve annulus area of ≤430 mm2 based on multi-detector computed tomography (MDCT), and appropriate anatomy for both the Medtronic Evolut PRO/PRO+ self-expanding (SE) and Edwards SAPIEN 3/3 Ultra balloon-expandable (BE) devices. The primary clinical outcome composite endpoint is defined as mortality, disabling stroke or heart failure rehospitalization at 12 months. The co-primary valve function composite endpoint is defined as bioprosthetic valve dysfunction (BVD) at 12 months which includes hemodynamic structural valve dysfunction (HSVD), defined as a mean gradient ≥20 mmHg, non-structural valve dysfunction (NSVD), defined as severe prothesis-patient mismatch (PPM) or ≥moderate aortic regurgitation (AR), thrombosis, endocarditis, and aortic valve re-intervention. Powered secondary endpoints will be assessed hierarchically.
Conclusions
The SMART trial will be the largest head-to-head comparative trial of transfemoral TAVR using the two most widely available contemporary TAVR devices in the setting of small aortic annuli and the largest trial to enroll primarily women.
Clinical trial registration
www.clinicaltrials.gov, NCT04722250.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 25 Sep 2021; epub ahead of print
Herrmann HC, Abdel-Wahab M, Attizzani GF, Batchelor W, ... Mehran R, Tchetche D
Am Heart J: 25 Sep 2021; epub ahead of print | PMID: 34587510
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Impact:
Abstract

Title: Temporal trends in utilization of transcatheter aortic valve replacement and patient characteristics: a nationwide study.

Strange JE, Sindet-Pedersen C, Gislason GH, Torp-Pedersen C, ... Søndergaard L, Olesen JB
Aim
To investigate trends in the utilization of transcatheter aortic valve replacement (TAVR) and changes in the characteristics of patients undergoing first-time TAVR.
Methods
Using Danish nationwide registers, we included all patients undergoing TAVR between 2008 and 2020. To compare patient characteristics, the study population was stratified according to calendar year of procedure: 2008-2010, 2011-2013, 2014-2016, and 2017-2020.
Results
We identified 6,097 patients undergoing TAVR with year-by-year increases in TAVR penetration rate. Over time, the age of the patients remained stable (2008-2010: median age 82 year [interquartile range (IQR): 77-86] vs. 2017-2020: median age 81 years [IQR: 77-85]). Moreover, there was an increase in male patients (2008-2010: 49.9% vs 2017-2020: 57.4%) and patients with diabetes (2008-2010: 14.2% vs. 2017-2020: 19.2%). Conversely, a history of stroke (2008-2010: 15.8% vs. 2017-2020: 13.1%), previous myocardial infarction (2008-2010: 22.4% vs. 2017-2020: 10.0%), heart failure (2008-2010: 40.5% vs. 2017-2020: 25.2%), and peripheral artery disease (2008-2010: 14.8% vs. 2017-2020: 10.4) decreased among patients.
Conclusions
TAVR utilization increased markedly in the years 2008-2020. Patients undergoing TAVR had less comorbidity over time while age remained stable. Thus, despite expanding to patients at lower surgical risk, TAVR is still offered mainly to older patients.
Condensed abstract
Guidelines lists transcatheter aortic valve replacement (TAVR) for treatment of symptomatic, severe aortic stenosis in patients at increased surgical risk. However, intermediate- and low-risk TAVR trials have recently been published, but it is largely unclear whether this has changed daily clinical practice. We identified 6,097 Danish patients undergoing first-time TAVR between 2008-2020. Over time, the overall comorbidity burden decreased with most noticeable declines for history of cardiovascular comorbidities and previous cardiac interventions while the age of patients at TAVR remained stable. Thus, despite expanding to patients at lower surgical risk, TAVR is still offered mainly to elderly patients.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 25 Sep 2021; epub ahead of print
Strange JE, Sindet-Pedersen C, Gislason GH, Torp-Pedersen C, ... Søndergaard L, Olesen JB
Am Heart J: 25 Sep 2021; epub ahead of print | PMID: 34587509
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Impact:
Abstract

Rationale and Pathways Forward in the Implementation of Coronary Artery Calcium-Based Enrichment of Randomized Trials.

Cainzos-Achirica M, Anugula D, Mszar R, Grandhi G, ... Bhatt DL, Nasir K
The Food and Drug Administration recommends prognostic enrichment of randomized controlled trials (RCTs), aimed at restricting the study population to participants most likely to have events and therefore derive benefit from a given intervention. The coronary artery calcium (CAC) score is powerful discriminator of cardiovascular risk, and in this review we discuss how CAC may be used to augment widely used prognostic enrichment paradigms of RCTs of add-on therapies in primary prevention. We describe recent studies in this space, with special attention to the ability of CAC to further stratify risk among guideline-recommended candidates for add-on risk-reduction therapies. Given the potential benefits in terms of sample size, cost reduction, and overall RCT feasibility of a CAC-based enrichment strategy, we discuss approaches that may help maximize its advantages while minimizing logistical barriers and other challenges. Specifically, use of already existing CAC data to avoid the need to re-scan participants with previously documented high CAC scores, use of clinical CAC databases to facilitate the identification of potential RCT participants, and implementation of machine learning approaches to measure CAC in existing computed tomography images performed for other purposes, will most likely boost the implementation of a CAC-based enrichment paradigm in future RCTs.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 25 Sep 2021; epub ahead of print
Cainzos-Achirica M, Anugula D, Mszar R, Grandhi G, ... Bhatt DL, Nasir K
Am Heart J: 25 Sep 2021; epub ahead of print | PMID: 34587511
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Impact:
Abstract

In vivo evidence of atherosclerotic plaque erosion and healing in patients with acute coronary syndrome using serial optical coherence tomography imaging.

Yin Y, Fang C, Jiang S, Wang J, ... Dai J, Yu B
Background
The EROSION study (Effective Anti-Thrombotic Therapy Without Stenting: Intravascular Optical Coherence Tomography-Based Management in Plaque Erosion) allowed us to observe the healing process of coronary plaque erosion in vivo. The present study aimed to investigate the incidence of newly formed healed plaque and different baseline characteristics of acute coronary syndrome (ACS) patients caused by plaque erosion with or without newly formed healed plaque using optical coherence tomography (OCT).
Methods
A total of 137 ACS patients with culprit plaque erosion who underwent pre-intervention OCT imaging and received no stent implantation were enrolled. Patients were stratified according to the presence or absence of newly formed healed phenotype at 1-month (137 patients) or 1-year OCT follow-up (52 patients). Patient\'s baseline clinical, angiographic, OCT characteristics and outcomes were compared.
Results
There were 55.5% (76/137) of patients developed healed plaque at 1 month, and 69.2% (36/52) of patients developed healed plaque at 1 year. Patients with newly formed healed plaque had larger thrombus burden, and lower degree of area stenosis (AS%) at baseline than those without, and thrombus burden and AS% were predictors of plaque healing. The healing process was accompanied by the significant increase of AS% and incidence of microchannels, and greater inflammatory response. The outcomes appeared to be similar between the two groups.
Conclusions
Newly formed healed plaque was found in more than half of ACS patients with plaque erosion without stenting. Patients with newly formed healed plaque had lower luminal stenosis and larger thrombus burden. During healing process, luminal stenosis increased gradually.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 24 Sep 2021; epub ahead of print
Yin Y, Fang C, Jiang S, Wang J, ... Dai J, Yu B
Am Heart J: 24 Sep 2021; epub ahead of print | PMID: 34582778
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Impact:
Abstract

Prevalent Pharmacotherapy of United States Fontan Survivors A study utilizing data from the MarketScan Commercial and Medicaid Claims Databases.

O\'Byrne ML, Faerber JA, Katcoff H, Huang J, ... Glatz AC, Goldberg DJ
Background
Survivors of Fontan palliation are at life-long risk of thrombosis, arrhythmia, and circulatory failure. To our knowledge, no studies have evaluated current United States pharmaceutical prescription practice in this population.
Methods
A retrospective observational study evaluating the prevalent use of prescription medications in children and adolescents with hypoplastic left heart syndrome or tricuspid atresia after Fontan completion (identified using ICD9/10 codes) was performed using data contained in the MarketScan® Commercial and Medicaid databases for the years 2013 through 2018. Cardiac pharmaceuticals were divided by class. Anticoagulant agents other than platelet inhibitors, which are not uniformly a prescription medication, were also studied. Associations between increasing age and the likelihood of a filled prescription for each class of drug were evaluated. Annualized retail costs of pharmaceutical regimens were calculated.
Results
A cohort of 4056 subjects [median age 12 years (IQR: 8-16), 61% male, 60% commercial insurance] was identified. Of the cohort, 50% received no prescription medications. Angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEi/ARB) (38%), diuretics (15%), and mineralocorticoid receptor antagonists (8%) were prescribed with the highest frequency. Pulmonary vasodilators were received by 6% of subjects. Older age was associated with increased likelihood of filled prescriptions for anticoagulants (p=0.008), antiarrhythmic agents, digoxin, ACEi/ARB, and beta blockers (each p<0.0001), but also lower likelihood of filled prescriptions for pulmonary vasodilators, conventional diuretics (both p<0.0001), and mineralocorticoid receptor antagonists (p=0.02).
Conclusion
Pharmaceuticals typically used to treat heart failure and pulmonary hypertension are the most commonly prescribed medications following Fontan palliation. While the likelihood of treatment with a particular class of medication is associated with the age of the patient, determining the optimal regimen for individual patients and the population at large is an important knowledge gap for future research.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 24 Sep 2021; epub ahead of print
O'Byrne ML, Faerber JA, Katcoff H, Huang J, ... Glatz AC, Goldberg DJ
Am Heart J: 24 Sep 2021; epub ahead of print | PMID: 34582777
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Impact:
Abstract

Trends in Hospitalizations for Heart Failure, Acute Myocardial Infarction, and Stroke in the United States from 2004-2018.

Salah HM, Khan Minhas AM, Khan MS, Khan SU, ... Pandey A, Fudim M
Aim
To determine the trends in hospitalizations for heart failure (HF), acute myocardial infarction (AMI), and stroke in the United States (US).
Method and results
A retrospective analysis of the National Inpatient Sample weighted data between January 1, 2004 and December 31, 2018 which included hospitalized adults ≥18 years with a primary discharge diagnosis of HF, AMI, or stroke using International Classification of Diseases-9/10 (ICD-9/10) administrative codes. Main outcomes were hospitalization for HF, AMI, and stroke per 1000 United States adults, length of stay (LOS), and in-hospital mortality. There were 33.4 million hospitalizations for HF, AMI, and stroke, with most being for HF (48%). After the initial decline in HF hospitalizations (5.3/1000 US adults in 2004 to 4/1000 US adults in 2013, p <0.001), there was a progressive increase in HF hospitalizations between 2013 and 2018 (4.0/1000 US adults in 2014 to 4.9 hospitalizations/1000 US adults in 2018; p=0.003). Hospitalization for AMI decreased (3.1 hospitalizations/1000 US adults in 2004 to 2.5 hospitalizations/1000 US adults in 2010, p<0.001) and remained stable between 2010-2018. There was no significant change for hospitalization for stroke between 2004-2011 (2.3 hospitalizations/1000 US adults in 2004 vs. 2.3 hospitalizations per 1000 US adults in 2018, p<0.001); however, there was a small but significant increase in hospitalization for stroke after 2011 that reached 2.5 hospitalizations/1000 US adults in 2018. Adjusted LOS and In-hospital mortality decreased for HF, AMI, and stroke hospitalizations.
Conclusions
In contrast to the trend of AMI and stroke hospitalizations, a progressive increase in hospitalizations for HF has occurred since 2013. From 2004 to 2018, in-hospital mortality has decreased for HF, AMI, and stroke hospitalizations.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 24 Sep 2021; epub ahead of print
Salah HM, Khan Minhas AM, Khan MS, Khan SU, ... Pandey A, Fudim M
Am Heart J: 24 Sep 2021; epub ahead of print | PMID: 34582776
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Impact:
Abstract

Predictors of Outcome in the ISCHEMIA-CKD Trial: Anatomy versus Ischemia.

Bainey KR, Fleg JL, Hochman JS, Kunichoff DF, ... Spertus JA, Bangalore S
Background
The ISCHEMIA-CKD (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches-Chronic Kidney Disease) trial found no advantage to an invasive strategy compared to conservative management in reducing all-cause death or myocardial infarction (D/MI). However, the prognostic influence of angiographic coronary artery disease (CAD) burden and ischemia severity remains unknown in this population. We compared the relative impact of CAD extent and severity of myocardial ischemia on D/MI in patients with advanced chronic kidney disease (CKD).
Methods
Participants randomized to invasive management with available data on coronary angiography and stress testing were included. Extent of CAD was defined by the number of major epicardial vessels with ≥50% diameter stenosis by QCA. Ischemia severity was assessed by site investigators as moderate or severe using trial definitions. The primary endpoint was D/MI.
Results
Of the 388 participants, 307 (79.1%) had complete coronary angiography and stress testing data. D/MI occurred in 104/307 participants (33.9%). Extent of CAD was associated with an increased risk of D/MI (p<0.001), while ischemia severity was not (p=0.249). These relationships persisted following multivariable adjustment. Using 0-vessel disease (VD) as reference, the adjusted hazard ratio (HR) for 1VD was 1.86, 95% confidence interval (CI) 0.94-3.68, p=0.073; 2VD: HR 2.13, 95% CI 1.10-4.12, p=0.025; 3VD: HR 4.00, 95% CI 2.06-7.76, p<0.001. Using moderate ischemia as the reference, the HR for severe ischemia was 0.84, 95% CI 0.54-1.30, p=0.427.
Conclusion
Among ISCHEMIA-CKD participants randomized to the invasive strategy, extent of CAD predicted D/MI whereas severity of ischemia did not.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 24 Sep 2021; epub ahead of print
Bainey KR, Fleg JL, Hochman JS, Kunichoff DF, ... Spertus JA, Bangalore S
Am Heart J: 24 Sep 2021; epub ahead of print | PMID: 34582775
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Impact:
Abstract

Trends in Transcatheter and Surgical Aortic Valve Replacement in the United States, 2008-2018.

Clark KA, Chouairi F, Kay B, Reinhardt SW, ... Ahmad T, Desai NR
We conducted a retrospective study using the NIS database from 2008-2018 to examine the most contemporary national hospitalization trends of transcatheter (TAVR) and surgical (SAVR) aortic valve replacement regarding volume, patient and hospital demographics and economics, resource utilization, total cost of stay, and in-hospital mortality. We demonstrate that TAVR procedures have been performed on a slow by steadily diversifying patient population while volume has grown significantly, while in-hospital mortality, length of stay, discharge home, and costs have improved, whereas these metrics have generally remained stable for SAVR. These trends will likely drive continued TAVR adoption, greatly expanding the overall aortic stenosis patient population eligible for AVR.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 23 Sep 2021; epub ahead of print
Clark KA, Chouairi F, Kay B, Reinhardt SW, ... Ahmad T, Desai NR
Am Heart J: 23 Sep 2021; epub ahead of print | PMID: 34571040
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Impact:
Abstract

Impact of vomiting on P2Y12 platelet inhibition in patients with ST-elevation myocardial infarction: a pre-specified sub-analysis of the ON-TIME 3 trial.

Tavenier AH, Hermanides RS, Ottervanger JP, Belitser SV, ... van \'t Hof AWJ, ON-TIME 3 investigators
Vomiting is associated with lower levels of ticagrelor concentration and higher platelet reactivity in the early hours of ST-elevation myocardial infarction. These results support reloading with a ticagrelor loading dose and/or treatment with intravenous platelet inhibitors when patients vomit.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 17 Sep 2021; epub ahead of print
Tavenier AH, Hermanides RS, Ottervanger JP, Belitser SV, ... van 't Hof AWJ, ON-TIME 3 investigators
Am Heart J: 17 Sep 2021; epub ahead of print | PMID: 34547260
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Impact:
Abstract

THE BLEEDING RISK TREATMENT PARADOX AT THE PHYSICIAN 1 AND HOSPITAL LEVEL: IMPLICATIONS FOR REDUCING BLEEDING IN PATIENTS UNDERGOING PCI.

Amin AP, Frogge N, Kulkarni H, Ridolfi G, ... Masoudi FA, Rao SV
Background
Bleeding is a common and costly complication of percutaneous coronary intervention (PCI). Bleeding avoidance strategies (BAS) are used paradoxically less in patients at high-risk of bleeding: \"bleeding risk-treatment paradox\" (RTP). We determined whether hospitals and physicians, who do not align BAS to PCI patients\' bleeding risk (i.e., exhibit a RTP) have higher bleeding rates.
Methods
We examined 28,005 PCIs from the NCDR CathPCI Registry for 7 hospitals comprising BJC HealthCare. BAS included transradial intervention (TRI), bivalirudin (BIV), and vascular closure devices (VCDs). Patients\' predicted bleeding risk was based on NCDR CathPCI bleeding model and categorized as low (<2.0%), moderate (2.0-6.4%), or high (≥6.5%) risk tertiles. BAS use was considered risk-concordant if: at least one BAS was used for moderate risk; two BAS were used for high risk and bivalirudin or VCDs were not used for low risk. Absence of risk-concordant BAS use was defined as RTP. We analyzed inter-hospital and inter-physician variation in RTP, and the association of RTP with post-PCI bleeding.
Results
Amongst 28,005 patients undergoing PCI by 103 physicians at seven hospitals, RTP was observed in 12,035 (43%) patients. RTP was independently associated with a higher likelihood of bleeding even after adjusting for predicted bleeding risk, mortality risk and potential sources of variation (OR 1.66, 95%CI 1.44-1.92, P<0.001). A higher prevalence of RTP strongly and independently correlated with worse bleeding rates, both at the physician-level (Wilk\'s Lambda 0.9502, F-value 17.21, p<0.0001) and the hospital-level (Wilk\'s Lambda 0.9899, F-value 35.68, p<0.0001). All the results were similar in a subset of PCIs conducted since 2015 - a period more reflective of the contemporary practice.
Conclusions
Bleeding RTP is a strong, independent predictor of bleeding. It exists at the level of physicians and hospitals: those with a higher rate of RTP had worse bleeding rates. These findings not only underscore the importance of recognizing bleeding risk upfront and using BAS in a risk-aligned manner, but also inform and motivate national efforts to reduce PCI-related bleeding.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 16 Sep 2021; epub ahead of print
Amin AP, Frogge N, Kulkarni H, Ridolfi G, ... Masoudi FA, Rao SV
Am Heart J: 16 Sep 2021; epub ahead of print | PMID: 34543645
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Impact:
Abstract

Left atrial appendage occlusion vs novel oral anticoagulation for stroke prevention in atrial fibrillation: rationale and design of the multicenter randomized occlusion-AF trial.

Korsholm K, Damgaard D, Valentin JB, Packer EJS, ... Johnsen SP, Nielsen-Kudsk JE
Background
The prevalence of atrial fibrillation (AF) is increasing globally, which is a major clinical and public health concern due to the 5-fold increased risk of stroke. Oral anticoagulation with novel oral anticoagulants (NOACs) is the current primary option for stroke prevention in patients with AF, although it increases the risk of major bleeding. Patients with prior ischemic cerebrovascular events are at particularly high risk of both recurrent ischemic events and major bleeding. Left atrial appendage occlusion (LAAO) provides an alternative option for stroke prevention in high-risk patients, however, with currently limited evidence. Thus, randomized trials comparing LAAO to NOACs are needed.
Objective
The Occlusion-AF trial is designed to assess whether LAAO is non-inferior to NOAC therapy for reduction of the combined endpoint of stroke, systemic embolism, major bleeding (Bleeding Academic Research Consortium ≥ 3) and all-cause mortality in patients with AF and a recent ischemic stroke or transient ischemic attack (TIA).
Methods and analysis
Investigator-initiated multicenter, multinational, randomized open-label non-inferiority trial with blinded outcome evaluation (PROBE design). Patients with documented AF, and an ischemic stroke or TIA within 6 months will be eligible for enrollment. Major exclusion criteria are modified Rankin Scale > 3 at enrollment, glomerular filtration rate < 15 ml/min, and life-expectancy less than 2 years. A total of 750 patients will be randomized 1:1 to receive either a NOAC or LAAO using the Amplatzer Amulet (Abbott, MN, USA) or Watchman FLX (Boston Scientific, MN, USA) with subsequent life-long aspirin 75 mg daily. Follow-up will be based on in-office and telephone follow-up in combination with long-term follow-up (10 years) through national hospital discharge registries in the individual Nordic countries. The primary outcome will be a composite endpoint of stroke, systemic embolism, major bleeding (BARC ≥ 3) and all-cause mortality at 2-year follow-up.
Conclusions
The Occlusion-AF trial is designed to compare LAAO to NOAC therapy for secondary stroke prevention in AF patients with a high risk of recurrent thromboembolic events, i.e. with previous ischemic stroke or TIA, and otherwise eligible for anticoagulation. The results are expected to contribute significantly to the understanding of the effects of LAAO compared to the standard contemporary pharmacological treatment in these patients.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 16 Sep 2021; 243:28-38
Korsholm K, Damgaard D, Valentin JB, Packer EJS, ... Johnsen SP, Nielsen-Kudsk JE
Am Heart J: 16 Sep 2021; 243:28-38 | PMID: 34537184
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Impact:
Abstract

Long-term Outcomes in Patients Treated with Flecainide for Atrial Fibrillation with Stable Coronary Artery Disease.

Burnham TS, May HT, Bair TL, Anderson JA, ... Steinberg BA, Bunch TJ
Background
Class 1C antiarrhythmic drugs(AAD) have been associated with harm in patients treated for ventricular arrhythmias with a prior myocardial infarction(MI). Consensus guidelines have advocated that these drugs not be used in patients with stable coronary artery disease(CAD). However, long-term data are lacking to know if unique risks exist when these drugs are used for atrial fibrillation(AF) in patients with CAD without a prior MI.
Methods
In 24,315 patients treated with the initiation of AADs, two populations were evaluated: 1. propensity-matched AF patients with CAD were created based upon AAD class (flecainide, n=1,114, versus class-3 AAD, n=1,114); 2. AF patients who had undergone a PCI or CABG (flecainide, n=150, and class-3 AAD, n=1,453). Outcomes at three years for mortality, heart failure (HF) hospitalization, ventricular tachycardia (VT), and MACE were compared between the groups.
Results
At 3 years, mortality (9.1% vs 19.3%, p<0.0001), HF hospitalization (12.5% vs 18.3%, p<0.0001), MACE (22.9% vs 36.6%, p<0.0001), and VT (5.8% vs 8.5%, p=0.02) rates were significantly lower in the flecainide group for population 1. In population 2, adverse event rates were also lower, although not significantly, in the flecainide compared to the class-3 AAD group for mortality (20.9% vs25.8%, p=0.26), HF hospitalization (24.5% vs 26.1%, p=0.73), VT (10.9% vs 14.7%, p=0.28) and MACE (44.5% vs 49.5%, p=0.32).
Conclusions
Flecainide in select patients with stable CAD for AF has a favorable safety profile compared to class-3 AADs. These data suggest the need for prospective trials of flecainide in AF patients with CAD to determine if the current guideline-recommended exclusion is warranted.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 15 Sep 2021; epub ahead of print
Burnham TS, May HT, Bair TL, Anderson JA, ... Steinberg BA, Bunch TJ
Am Heart J: 15 Sep 2021; epub ahead of print | PMID: 34537183
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Impact:
Abstract

Rationale and Design of the Groningen Intervention Study for the Preservation of Cardiac Function with Sodium Thiosulfate after ST-segment Elevation Myocardial Infarction (GIPS-IV) Trial.

de Koning MLY, van Dorp P, Assa S, Hartman MHT, ... Lipsic E, van der Harst P
Rationale
Ischemia and subsequent reperfusion cause myocardial injury in patients presenting with ST-segment elevation myocardial infarction (STEMI). Hydrogen sulfide (H2S) reduces \"ischemia-reperfusion injury\" in various experimental animal models, but has not been evaluated in humans. This trial will examine the efficacy and safety of the H2S-donor sodium thiosulfate (STS) in patients presenting with a STEMI.
Study design
The Groningen Intervention study for the Preservation of cardiac function with STS after STEMI (GIPS-IV) trial (NCT02899364) is a double-blind, randomized, placebo-controlled, multicenter trial, which will enroll 380 patients with a first STEMI. Patients receive STS 12.5 gram intravenously or matching placebo in addition to standard care immediately at arrival at the catheterization laboratory after providing consent. A second dose is administered 6 hours later at the coronary care unit. The primary endpoint is myocardial infarct size as quantified by cardiac magnetic resonance imaging 4 months after randomization. Secondary endpoints include the effect of STS on peak CK-MB during admission and left ventricular ejection fraction and NT-proBNP levels at 4 months follow-up. Patients will be followed-up for 2 years to assess clinical endpoints.
Conclusions
The GIPS-IV trial is the first study to determine the effect of a H2S-donor on myocardial infarct size in patients presenting with STEMI.

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Am Heart J: 13 Sep 2021; epub ahead of print
de Koning MLY, van Dorp P, Assa S, Hartman MHT, ... Lipsic E, van der Harst P
Am Heart J: 13 Sep 2021; epub ahead of print | PMID: 34534493
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Impact:
Abstract

The Importance of the Design of Observational Studies in Comparative Effectiveness Research: Lessons from the GARFIELD-AF and ORBIT-AF registries.

Farjat AE, Virdone S, Thomas LE, Kakkar AK, Pieper KS, Piccini JP
Randomized controlled trials (RCTs) are considered the gold standard for estimating the effectiveness of a treatment. However, in many instances they are impractical to conduct because of time limitations, cost restrictions, or ethical reasons. As a consequence, non-randomized observational studies have an important role in comparative effectiveness and safety research since they can address issues that would not be possible using conventional RCT methodology. Observational studies can be strategically designed to reduce the risk of potential sources of bias by emulating the design principles of an equivalent but ideal randomized trial - the target trial - that would answer the research question of interest. In this article, we review some of the necessary components of observational studies required for valid causal inference within the framework of target trial emulation, so as to avoid common methodological pitfalls of study design. We discuss the assumptions of consistency, time-zero specification, exchangeability and positivity. To illustrate these concepts in a context where existing knowledge is well-established through clinical trials, we evaluate and compare the treatment effects of vitamin K antagonists (VKA) against no VKA (No VKA) on the treatment of atrial fibrillation (AF) from two real-world observational studies, namely the GARFIELD-AF and ORBIT-AF registries. Results are compared with those of published RCTs.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 12 Sep 2021; epub ahead of print
Farjat AE, Virdone S, Thomas LE, Kakkar AK, Pieper KS, Piccini JP
Am Heart J: 12 Sep 2021; epub ahead of print | PMID: 34529945
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Impact:
Abstract

Effect of intensive versus limited monitoring on clinical trial conduct and outcomes: A randomized trial.

Butala NM, Song Y, Shen C, Cohen DJ, Yeh RW
Background
Regulatory agencies have endorsed more limited approaches to clinical trial site monitoring. However, the impact of different monitoring strategies on trial conduct and outcomes is unclear.
Methods
We conducted a patient-level block randomized controlled trial evaluating the effect of intensive versus limited monitoring on cardiovascular clinical trial conduct and outcomes nested within the CoreValve Continued Access and Expanded Use Studies. Intensive monitoring included complete source data verification of all critical datapoints whereas limited monitoring included automated data checks only. This study\'s endpoints included clinical trial outcome ascertainment as well as monitoring action items, protocol deviations, and adverse event ascertainment.
Results
A total of 2708 patients underwent transcatheter aortic valve replacement (TAVR) and were randomized to either intensive monitoring (n=1354) or limited monitoring (n=1354). Monitoring action items were more common with intensive monitoring (52% vs 15%; p<0.001), but there was no difference in the percentage of patients with any protocol deviation (91.6% vs 90.4%; p=0.314). The reported incidence of trial outcomes between intensive and limited monitoring was similar for mortality (30 days: 4.8% vs. 5.5%, p=0.442; 1 year: 20.3% vs 21.3%, p=0.473) and stroke (30 days: 2.8% vs 2.4%, p=0.458), as well as most secondary trial outcomes with the exception of bleeding (intensive: 36.3% vs limited: 32.0% at 30 days, p=0.019). There was a higher reported incidence of cardiac adverse events reported in the intensive monitoring group at 1 year (76.7% vs 72.4%; p=0.019).
Conclusion
Tailored limited monitoring strategies can be implemented without influencing the integrity of TAVR trial outcomes.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 12 Sep 2021; epub ahead of print
Butala NM, Song Y, Shen C, Cohen DJ, Yeh RW
Am Heart J: 12 Sep 2021; epub ahead of print | PMID: 34529944
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Impact:
Abstract

A global perspective of racial differences and outcomes in patients presenting with acute heart failure.

Tromp J, Ouwerkerk W, Cleland JGF, Chandramouli C, ... Filippatos G, Lam CS
Important racial differences in characteristics, treatment, and outcomes of patients with acute heart failure (AHF) have been described. The objective of this analysis of the International Registry to assess medical Practice with longitudinal observation for Treatment of Heart Failure (REPORT-HF) registry was to investigate racial differences in patients with AHF according to country income level.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 09 Sep 2021; 243:11-14
Tromp J, Ouwerkerk W, Cleland JGF, Chandramouli C, ... Filippatos G, Lam CS
Am Heart J: 09 Sep 2021; 243:11-14 | PMID: 34516969
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Impact:
Abstract

Performance of the ESC 0/2h-algorithm using high-sensitivity cardiac troponin I in the early diagnosis of myocardial infarction.

Koechlin L, Boeddinghaus J, Nestelberger T, Lopez-Ayala P, ... Mueller C, APACE investigators
The 2020 guidelines of the European Society of Cardiology (ESC) recommend a novel ESC 0/2h-algorithm as the preferred alternative to the ESC 0/1h-algorithm in the early triage for rule-out and/or rule-in of Non-ST-segment-elevation myocardial infarction (NSTEMI). The aim was to prospectively validate the performance of the ESC 0/2h-algorithm using the high-sensitivity cardiac troponin I (hs-cTnI) assay (ARCHITECT) in an international, multicenter diagnostic study enrolling patients presenting with acute chest discomfort to the emergency department.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 08 Sep 2021; 242:132-137
Koechlin L, Boeddinghaus J, Nestelberger T, Lopez-Ayala P, ... Mueller C, APACE investigators
Am Heart J: 08 Sep 2021; 242:132-137 | PMID: 34508692
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Impact:
Abstract

Initial rhythm control with cryoballoon ablation vs drug therapy: Impact on quality of life and symptoms.

Pavlovic N, Chierchia GB, Velagic V, Hermida JS, ... Kuniss M, Cryo-FIRST Investigators
Background
Cryoballoon ablation (CBA) as a first-line rhythm control strategy is superior to antiarrhythmic drugs (AADs) for preventing atrial fibrillation (AF) recurrence; the impact of first-line CBA on quality of life (QoL) and symptoms has not been well characterized.
Methods
Patients aged 18 to 75 with symptomatic paroxysmal AF naïve to rhythm control therapy were randomized (1:1) to CBA (Arctic Front Advance, Medtronic) or AAD (Class I or III). Symptoms and QoL were assessed at baseline, 1, 3, 6, 9, and 12 months using the EHRA classification and Atrial Fibrillation Effect on QualiTy-of-Life (AFEQT) and SF-36v2 questionnaires. Symptomatic palpitations were evaluated via patient diary.
Results
Overall, 107 patients were randomized to CBA and 111 to AAD; crossovers occurred in 9%. Larger improvements in the AFEQT summary, subscale and treatment satisfaction scores were observed at 12 months with CBA vs AAD (all P <0.05). At 12 months, the mean adjusted difference in the AFEQT summary score was 9.9 points higher in the CBA group (95% CI: 5.5 -14.2, P <0.001). Clinically important improvements in the SF-36 physical and mental component scores were observed at 12 months in both groups, with no significant between group differences at this timepoint. In the CBA vs AAD group, larger improvements in EHRA class were observed at 6, 9 and 12 months (P <0.05) and the incidence rate of symptomatic palpitations was lower (4.6 vs 15.2 days/year post-blanking; IRR: 0.30, P <0.001).
Conclusions
In patients with symptomatic AF, first-line CBA was superior to AAD for improving AF-specific QoL and symptoms.
Trial registration
ClinicalTrials.gov number: NCT01803438.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 07 Sep 2021; 242:103-114
Pavlovic N, Chierchia GB, Velagic V, Hermida JS, ... Kuniss M, Cryo-FIRST Investigators
Am Heart J: 07 Sep 2021; 242:103-114 | PMID: 34508694
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Impact:
Abstract

Inhibition of p38 MAP Kinase in Patients with ST-Elevation Myocardial Infarction - Findings from the LATITUDE TIMI 60 Trial.

Cavender MA, O\'Donoghue M, Abbate A, Aylward P, ... Sabatine MS, Morrow DA
Background
p38 mitogen activated kinase (MAPK) mediates the response to pro-inflammatory cytokines following myocardial infarction (MI) and is inhibited by losmapimod.
Methods
LATITUDE-TIMI 60 (ClinicalTrials.gov NCT02145468) randomized patients with MI to losmapimod or placebo for 12 weeks (24 weeks total follow-up). In this pre-specified analysis, we examined outcomes based on MI type [ST-segment elevation MI (STEMI) (865, 25%) and non-STEMI (2624, 75%)].
Results
In patients with STEMI, inflammation, measured by hs-CRP, was significantly attenuated with losmapimod at 48 hours (p<0.001) and week 12 (p=0.01). Losmapimod lowered NT-proBNP in patients with STEMI at 48 hours (p=0.04) and week 12 (p=0.02). The effects of losmapimod on CV death (CVD), MI, or severe recurrent ischemia requiring urgent coronary artery revascularization at 24 weeks [MACE] differed in patients with STEMI (7.0% vs. 10.8%; HR 0.65, 95%CI 0.41-1.03; p=0.06) and NSTEMI (11.4% vs. 8.5%; HR 1.30, 95%CI 1.02-1.66; p=0.04; p[int]=0.009). CVD or HHF among patients with STEMI were 5.6% (losmapimod) and 8.3% (placebo) (HR 0.66; 95%CI 0.40-1.11; p=0.12) and in NSTEMI were 4.8% (losmapimod) and 4.4% (placebo) (HR 1.09; 95%CI 0.76-1.56) in patients with NSTEMI.
Conclusions
Patients with STEMI treated with losmapimod had an attenuated inflammatory response. Our collective findings raise the hypothesis that mitigating the inflammatory response may result in different outcomes in patients with STEMI and NSTEMI. While the difference in outcomes is exploratory, these findings do support separate examination of patients with STEMI and NSTEMI and increased emphasis on heart failure in future investigation of modulators of inflammation in MI.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 07 Sep 2021; epub ahead of print
Cavender MA, O'Donoghue M, Abbate A, Aylward P, ... Sabatine MS, Morrow DA
Am Heart J: 07 Sep 2021; epub ahead of print | PMID: 34508693
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Impact:
Abstract

Population health management of low-density lipoprotein cholesterol via a remote, algorithmic, navigator-executed program.

Plutzky J, Benson MD, Chaney K, Bui TV, ... MacRae CA, Scirica BM
Background
Implementation of guideline-directed cholesterol management remains low despite definitive evidence establishing such measures reduce cardiovascular (CV) events, especially in high atherosclerotic CV disease (ASCVD) risk patients. Modern electronic resources now exist that may help improve health care delivery. While electronic medical records (EMR) allow for population health screening, the potential for coupling EMR screening to remotely delivered algorithmic population-based management has been less studied as a way of overcoming barriers to optimal cholesterol management.
Methods
In an academically affiliated healthcare system, using EMR screening, we sought to identify 1,000 high ASCVD risk patients not meeting guideline-directed low-density lipoprotein-cholesterol (LDL-C) goals within specific system-affiliated primary care practices. Contacted patients received cholesterol education and were offered a remote, guideline-directed, algorithmic cholesterol management program executed by trained but non-licensed \"navigators\" under professional supervision. Navigators used telephone, proprietary software and internet resources to facilitate algorithm-driven, guideline-based medication initiation/titration, and laboratory testing until patients achieved LDL-C goals or exited the program. As a clinical effectiveness program for cholesterol guideline implementation, comparison was made to those contacted patients who declined program-based medication management, and received education only, along with their usual care.
Results
1021 patients falling into guideline-defined high ASCVD risk groups warranting statin therapy (ASCVD, type 2 diabetes, LDL ≥ 190 mg/dL, calculated 10-year ASCVD risk ≥7.5%) and not achieving guideline-defined target LDL-C levels and/or therapy were identified and contacted. Among the 698 such patients who opted for program medication management, significant LDL-C reductions occurred in the total cohort (mean -65.4 mg/dL, 45% decrease), and each high ASCVD risk subgroup: ASCVD (-57.2 mg/dL, -48.0%); diabetes mellitus (-53.1 mg/dL, -40.0%); severe hypercholesterolemia (-76.3 mg/dL, -45.7%); elevated ASCVD 10-year risk (-62.8 mg/dL, -41.1%) (P<0.001 for all), without any significant complications. Among 20% of participants with reported statin intolerance, average LDL-C decreased from baseline 143 mg/dL to 85 mg/dL using mainly statins and ezetimibe, with limited PCSK9 inhibitor use. In comparison, eligible high ASCVD risk patients who were contacted but opted for education only, a 17% LDL-C decrease occurred over a similar timeframe, with 80% remaining with an LDL-C over 100 mg/dL.
Conclusions
A remote, algorithm-driven, navigator-executed cholesterol management program successfully identified high ASCVD risk undertreated patients using EMR screening and was associated with significantly improved guideline-directed LDL-C control, supporting this approach as a novel strategy for improving health care access and delivery.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 02 Sep 2021; 243:15-27
Plutzky J, Benson MD, Chaney K, Bui TV, ... MacRae CA, Scirica BM
Am Heart J: 02 Sep 2021; 243:15-27 | PMID: 34481756
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Impact:
Abstract

Reducing disparities in adverse pregnancy outcomes in the United States.

Shah LM, Varma B, Nasir K, Walsh MN, ... Mehta LS, Sharma G
There is growing evidence that rural and racial disparities and social determinants of health (SDOH) impact adverse pregnancy outcomes (APOs) and overall maternal mortality in the United States. These APOs, such as preeclampsia, preterm birth, and intrauterine growth restriction, are in-turn associated with increased risk of future cardiovascular disease (CVD) later in life. Importantly, SDOH such as socioeconomic disadvantages, poor health literacy, transportation barriers, lack of access to adequate health care, food insecurity, and psychosocial stressors have cascading effects on APOs and downstream cardiovascular health. These SDOH are also deeply intertwined with and compounded by existing racial and rural disparities. Pregnancy thus provides a unique opportunity to identify at-risk women from a social determinants perspective, and provide early interventions to optimize long-term CVD and mitigate cardiovascular health disparities. Addressing the challenges posed by these disparities requires a multi-pronged approach and involves national, regional, and individual level solutions. Eliminating disparities will necessitate a nationwide obligation to ensure health care equity via enhanced health insurance coverage, resource investment, and public and clinician accountability.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 01 Sep 2021; 242:92-102
Shah LM, Varma B, Nasir K, Walsh MN, ... Mehta LS, Sharma G
Am Heart J: 01 Sep 2021; 242:92-102 | PMID: 34481757
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Impact:
Abstract

Medically Ill hospitalized Patients for COVID-19 THrombosis Extended ProphyLaxis with rivaroxaban ThErapy: Rationale and Design of the MICHELLE Trial.

Ramacciotti E, Agati LB, Calderaro D, Volpiani GG, ... Spyropoulos AC, Lopes RD
Background
The devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis.
Design
This study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35 ± 4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 ± 4 posthospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria.
Summary
The MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice.1.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 31 Aug 2021; 242:115-122
Ramacciotti E, Agati LB, Calderaro D, Volpiani GG, ... Spyropoulos AC, Lopes RD
Am Heart J: 31 Aug 2021; 242:115-122 | PMID: 34480880
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Impact:
Abstract

Increased risk of ischemic stroke and systemic embolism in hyperthyroidism-related atrial fibrillation: A nationwide cohort study.

Kim K, Yang PS, Jang E, Yu HT, ... Lip GYH, Joung B
Background
We aimed to evaluate the long-term risk of ischemic stroke/systemic embolism of hyperthyroidism-related AF.
Methods
This retrospective population-based cohort study included records of 1,034,099 atrial fibrillation patients between 2005 and 2016 from the Korean National Health Insurance Service database. After exclusion, we identified 615,724 oral anticoagulation-naïve patients aged ≥18 years with new-onset non-valvular atrial fibrillation, of whom 20,773 had hyperthyroidism-related atrial fibrillation. After 3:1 propensity score matching, ischemic stroke and systemic embolism occurrences were compared between hyperthyroidism-related and non-hyperthyroidism-related (\"nonthyroidal\") atrial fibrillation patients.
Results
After exclusion, we identified 615,724 oral anticoagulation-naïve AF patients of whom 20,773 had hyperthyroidism-related AF. Median follow-up duration was 5.9 years. Hyperthyroidism-related AF patients had significantly higher risks of ischemic stroke and systemic embolism than nonthyroidal AF patients (1.83 vs 1.62 per 100-person year, hazard ratio[HR], 1.13; 95% confidence interval[CI], 1.07 to 1.19; P < 0.001). This risk was 36% higher in hyperthyroidism-related than in nonthyroidal AF patients within 1 year of atrial fibrillation diagnosis (3.65 vs 2.67 per 100-person year, HR, 1.36; 95% CI, 1.24 - 1.50; P < 0.001). This difference was also observed in the CHA2DS2-VASc score subgroup analysis. The risk of ischemic stroke and systemic embolism significantly decreased in patients treated for hyperthyroidism (HR, 0.64; 95% CI, 0.58 to 0.70; P < 0.001).
Conclusions
Hyperthyroidism-related AF patients have high risks of ischemic stroke and systemic embolism like nonthyroidal AF, especially when initially diagnosed. This risk is reduced by treating hyperthyroidism.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 31 Aug 2021; 242:123-131
Kim K, Yang PS, Jang E, Yu HT, ... Lip GYH, Joung B
Am Heart J: 31 Aug 2021; 242:123-131 | PMID: 34480879
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Impact:
Abstract

Relationship of ejection fraction and natriuretic peptide trajectories in heart failure with baseline reduced and mid-range ejection fraction.

Bilchick KC, Stafford P, Laja O, Elumogo C, ... Breathett K, Mazimba S
Background
The prognostic importance of trajectories of neurohormones relative to left ventricular function over time in heart failure with reduced and mid-range EF (HFrEF and HFmrEF) is poorly defined.
Objective
To evaluate left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP) trajectories in HFrEF and HFmrEF.
Methods
Analyses of LVEF and BNP trajectories after incident HF admissions presenting with abnormal LV systolic function were performed using 3 methods: a Cox proportional hazards model with time-varying covariates, a dual longitudinal-survival model with shared random effects, and an unsupervised analysis to capture 3 discrete trajectories for each parameter.
Results
Among 1,158 patients (68.9 ± 13.0 years, 53.3% female), both time-varying LVEF measurements (P=.001) and log-transformed BNP measurements (p-values=2 × 10-16) were independently associated with survival during 6 years after covariate adjustment. In the dual longitudinal/survival model, both LVEF and BNP trajectories again were independently associated with survival (P<.0001 in each model); however, LVEF was more dynamic than BNP (P <.0001 for time covariate in LVEF longitudinal model versus P=.88 for the time covariate in BNP longitudinal model). In the unsupervised analysis, 3 discrete LVEF trajectories (dividing the cohort into approximately thirds) and 3 discrete BNP trajectories were identified. Discrete LVEF and BNP trajectories had independent prognostic value in Kaplan-Meier analyses (P<.0001), and substantial membership variability across BNP and LVEF trajectories was noted.
Conclusion
Although LVEF trajectories have greater temporal variation, BNP trajectories provide additive prognostication and an even stronger association with survival times in heart failure patients with abnormal LV systolic function.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 24 Aug 2021; 243:1-10
Bilchick KC, Stafford P, Laja O, Elumogo C, ... Breathett K, Mazimba S
Am Heart J: 24 Aug 2021; 243:1-10 | PMID: 34453882
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Impact:
Abstract

Cardiovascular and major bleeding outcomes with antiplatelet and direct oral anticoagulants in patients with acute coronary syndrome and atrial fibrillation: A population-based analysis.

Dawwas GK, Barnes GD, Dietrich E, Cuker A, ... Genuardi MV, Lewis JD
Background
Direct oral anticoagulants (DOACs) are replacing warfarin for stroke prevention in patients with atrial fibrillation (AF).
Objective
To assess the effectiveness and safety of concomitant treatment with antiplatelet-DOAC compared to antiplatelet-warfarin in patients with acute coronary syndrome (ACS) and AF.
Design
Retrospective propensity score-matched cohort study using United States-based commercial healthcare database from January 2016 to June 2019.
Participants
New-users of antiplatelet-DOAC and antiplatelet-warfarin who initiated the combined therapy within 30 days following incident ACS diagnosis.
Measurements
Primary study outcomes were recurrent cardiovascular diseases (CVD) (ie, a composite of stroke and myocardial infarction) and major bleeding events identified via discharge diagnoses. We controlled for potential confounders via propensity score matching (PSM). We generated marginal hazard ratios (HRs) via Cox proportional hazards regression using a robust variance estimator while adjusting for calendar time.
Results
After PSM, a total of 2,472 persons were included (1,236 users of antiplatelet-DOAC and 1,236 users of antiplatelet-warfarin). The use of antiplatelet-DOAC (vs. antiplatelet-warfarin) was associated with a reduced rate of recurrent CVD (adjusted HR 0.72, 95% confidence interval [CI], 0.56-0.92) and major bleeding events (adjusted HR, 0.49, 95% CI 0.33-0.72).
Limitations
Residual confounding.
Conclusions
In real-world data of AF patients with concurrent ACS, the use of antiplatelet-DOAC following ACS diagnosis was associated with a lower rate of recurrent CVD and major bleeding events compared with antiplatelet-warfarin. These findings highlight a potential promising role for DOACs in patients with ACS and AF requiring combined antiplatelet therapy.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 23 Aug 2021; 242:71-81
Dawwas GK, Barnes GD, Dietrich E, Cuker A, ... Genuardi MV, Lewis JD
Am Heart J: 23 Aug 2021; 242:71-81 | PMID: 34450051
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Impact:
Abstract

Sex-based difference in fractional flow reserve and its impact on clinical outcomes.

Alkhalil M, Thomas G, Spence MS, Owens C, McKavanagh P
Background
Obesity is a real public health problem and is of growing concern. People are resorting to surgical or endoscopic means to fight against overweight and obesity. In recent years, there has been a marked increase in the use of these means and in particular the insertion of a gastric balloon which seems to present less risk than surgical methods. Renal complications from intragastric balloon placement are extremely rare. We report here the case of compression of the left renal vein revealed by lumbar pain and hematuria in an overweight 39-year-old woman who benefited from the balloon gastric placement one month before symptoms. The scanner made the diagnosis and showed a good evolution after the withdrawal of the balloon.
Methods
This was a prespecified and retrospective analysis of all consecutive patients who underwent FFR assessment for intermediate coronary lesions between January 2014 and December 2015. The primary endpoint was defined as the 1-year composite of cardiac death, vessel-related myocardial infarction, and clinically-driven target vessel revascularization.
Results
In 1554 lesions (23% in women), FFR was lower in men [0.83 ±0.09 vs 0.85 ±0.08, P = .004] driven by LAD values (for LAD P < .001, LCx or RCA P> .40). In proximal lesions (PLs), FFR was lower in men [0.83 ±0.10 vs 0.85 ±0.08, P = .004] with comparable values in non-PLs [0.84 ±0.09 vs 0.85 ±0.08, P = .36]. In PLs, the primary endpoint was higher in women [HR(adjusted) 3.18 (1.08-9.37), P = .035] with comparable outcomes in non-PLs (P = .032 for interaction). In deferred lesions, the primary endpoint was higher in women [HR(adjusted) 2.73 (1.10-6.74), P = .03] with no differences in revascularized lesions across sex (P = .02 for interaction). Results were consistent when using propensity score matching analysis.
Conclusions
There is a sex-based difference in FFR, particularly in stenoses subtending large myocardium, and more evident in deferred lesions.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 23 Aug 2021; 242:24-32
Alkhalil M, Thomas G, Spence MS, Owens C, McKavanagh P
Am Heart J: 23 Aug 2021; 242:24-32 | PMID: 34450050
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Impact:
Abstract

Atrial fibrillation burden and cognitive decline in elderly patients undergoing continuous monitoring.

Bonnesen MP, Diederichsen SZ, Isaksen JL, Frederiksen KS, ... Brandes A, Svendsen JH
Aims
To study the relationship between subclinical atrial fibrillation (AF) and changes in cognitive function in a large cohort of individuals with stroke risk factors.
Methods
Individuals with no prior AF diagnosis but with risk factors for stroke were recruited to undergo annual cognitive assessment with the Montreal Cognitive Assessment (MoCA) along with implantable loop recorder (ILR) monitoring for AF for 3 years. If AF episodes lasting ≥6 minutes were detected, oral anticoagulation (OAC) treatment was initiated.
Results
A total of 1194 participants (55.2 % men, mean age 74.5 (±3.9)) had a combined duration of heart rhythm monitoring of ≈1.3 million days. Among these, 339 participants (28.3%) had adjudicated AF, with a median AF burden of 0.072% (0.02, 0.39), and 324 (96%) initiated OAC. When stratifying the participants into AF burden groups (No AF, AFlow (AF burden <0.25%), and AFhigh, (AF burden >0.25%)), only participants in the AFlow group had a decrease in MoCA score over time (P = .03), although this was not significant after adjustment for stroke risk factors. A subgroup analysis of 175 participants (14.6%) with a MoCA <26 at 3 years found no association to AF diagnosis or burden.
Conclusions
In a high-risk population, subclinical AF detected by continuous monitoring and subsequently treated with OAC was not associated with a significant change in MoCA score over a 3-year period.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 20 Aug 2021; 242:15-23
Bonnesen MP, Diederichsen SZ, Isaksen JL, Frederiksen KS, ... Brandes A, Svendsen JH
Am Heart J: 20 Aug 2021; 242:15-23 | PMID: 34428441
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Impact:
Abstract

Text messages for primary prevention of cardiovascular disease: The TextMe2 randomized clinical trial.

Klimis H, Thiagalingam A, McIntyre D, Marschner S, Von Huben A, Chow CK
Background
Primary prevention guidelines emphasize the importance of lifestyle modification, but many at high-risk have suboptimal cardiovascular risk factor (CVRF) control. Text message support may improve control, but the evidence is sparse. Our objective was to determine the impact of text messages on multiple CVRFs in a moderate-high risk primary prevention cohort.
Methods
This study was a single-blind randomized clinical trial comparing semi-personalized text message-based support to standard care. A random sample of adults with 10-year absolute cardiovascular risk score ≥10% and without coronary heart disease, referred from February 2019 to January 2020, were recruited from an outpatient cardiology clinic in a large tertiary hospital in Sydney, Australia. Patients were randomized 1:1 to intervention or control. Intervention participants received 4 texts per week over 6 months, and standard care, with content covering: diet, physical activity, smoking, general cardiovascular health, and medication adherence. Controls received standard care only. Content was semipersonalized (smoking status, vegetarian or not-vegetarian, physical ability, taking medications or not) and delivered randomly using automated software. The primary outcome was the difference in the proportion of patients who have ≥3 uncontrolled CVRFs (out of: low-density lipoprotein cholesterol >2.0 mmol/L, blood pressure >140/90 mm Hg, body mass index ≥25 kg/m2, physical inactivity, current smoker) at 6 months adjusted for baseline. Secondary outcomes included differences in biomedical and behavioral CVRFs.
Results
Among 295 eligible participants, 246 (mean age, 58.6 ± 10.7 years; 39.4% female) were randomized to intervention (n = 124) or control (n = 122). At 6 months, there was no significant difference in the proportion of patients with ≥3 uncontrolled CVRFs (adjusted relative risk [RR] 0.98; 95% confidence interval [CI] 0.75-1.29; P = .88). Intervention participants were less likely to be physically inactive (adjusted RR 0.72; 95% CI 0.57-0.92; P = .01), but there were no significant changes in other single CVRFs. More intervention participants reduced the number of uncontrolled CVRFs at 6-months from baseline than controls (86% vs 75%; RR 1.15; 95% CI 1.00-1.32; P = .04).
Conclusions
In moderate-high cardiovascular risk primary prevention, text message-based support did not significantly reduce the proportion of patients with ≥3 uncontrolled CVRFs. However, the program did motivate behavior change and significantly improved cardiovascular risk factor control overall. Larger multicenter studies are needed.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 20 Aug 2021; 242:33-44
Klimis H, Thiagalingam A, McIntyre D, Marschner S, Von Huben A, Chow CK
Am Heart J: 20 Aug 2021; 242:33-44 | PMID: 34428440
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Abstract

The NHLBI Study on Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC): Design and Objectives: Design and Rationale of the MUSIC Study.

Truong DT, Trachtenberg FL, Pearson GD, Dionne A, ... Taylor M, Newburger JW
Background
The Long-terM OUtcomes after the Multisystem Inflammatory Syndrome In Children (MUSIC) study aims to characterize the frequency and time course of acute and long-term cardiac and non-cardiac sequelae in MIS-C, which are currently poorly understood.
Methods
This multicenter observational cohort study will enroll at least 600 patients <21 years old who meet the Centers for Disease Control and Prevention case definition of MIS-C across multiple North American centers over 2 years. The study will collect detailed hospital and follow-up data for up to 5 years, and optional genetic testing. Cardiac imaging at specific time points includes standardized echocardiographic assessment (all participants) and cardiac magnetic resonance imaging (CMR) in those with left ventricular ejection fraction (LVEF) <45% during the acute illness. The primary outcomes are the worst LVEF and the highest coronary artery z-score of the left anterior descending or right coronary artery. Other outcomes include occurrence and course of non-cardiac organ dysfunction, inflammation, and major medical events. Independent adjudication of cases will classify participants as definite, possible, or not MIS-C. Analysis of the outcomes will include descriptive statistics and regression analysis with stratification by definite or possible MIS-C. The MUSIC study will provide phenotypic data to support basic and translational research studies.
Conclusions
The MUSIC study, with the largest cohort of MIS-C patients and the longest follow-up period to date, will make an important contribution to our understanding of the acute cardiac and non-cardiac manifestations of MIS-C and the long-term effects of this public health emergency.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 17 Aug 2021; epub ahead of print
Truong DT, Trachtenberg FL, Pearson GD, Dionne A, ... Taylor M, Newburger JW
Am Heart J: 17 Aug 2021; epub ahead of print | PMID: 34418362
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Abstract

Patient evaluation of a virtual visit program for adults with congenital heart disease.

Krishnamurthy Y, Pagliaro JA, Grady CB, Katz N, Bunn D, Bhatt AB
Background
Improved longevity for adults with congenital heart disease (ACHD) necessitates regular, longitudinal care for this population. Telemedicine has emerged as a strategy to increase access to subspecialty care. We evaluated patient experience with a virtual visit program in the pre-COVID era to identify patient-centered benefits and limitations.
Methods
We enrolled patients for 30-minute synchronous videoconferencing virtual visits at our institution between October 2013 and March 2019. All patients were Massachusetts residents. Patients were surveyed and their characteristics were abstracted from electronic medical records.
Results
A total of 264 virtual visits were conducted among 174 patients with a median age of 40 years. Patients traveled a median of 70 miles for in-person visits. Many visits were to review patient data (47%), and most individuals had moderate complexity CHD (45%). Patients reported very high satisfaction with a median visit rating of 10. Patients mostly preferred virtual visits when considering convenience and cost. No difference in preference to in-person visits was reported when considering sharing private information, confidence that concerns would be addressed, and overall visit quality. In-person visits were still preferred for personal connections and showing a physical problem.
Conclusion
We find that patients are highly satisfied with virtual visits. ACHD programs should consider blended virtual and in-person care. Long-term regulatory provisions will further improve care through the expansion of telemedicine in the post-COVID era.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 13 Aug 2021; 242:138-145
Krishnamurthy Y, Pagliaro JA, Grady CB, Katz N, Bunn D, Bhatt AB
Am Heart J: 13 Aug 2021; 242:138-145 | PMID: 34400141
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Abstract

Cardiac pathology 6 months after hospitalization for COVID-19 and association with the acute disease severity.

Myhre PL, Heck SL, Skranes JB, Prebensen C, ... Lyngbakken MN, Omland T
Background
Coronavirus disease 2019 (COVID-19) may cause myocardial injury and myocarditis, and reports of persistent cardiac pathology after COVID-19 have raised concerns of long-term cardiac consequences. We aimed to assess the presence of abnormal cardiovascular resonance imaging (CMR) findings in patients recovered from moderate-to-severe COVID-19, and its association with markers of disease severity in the acute phase.
Methods
Fifty-eight (49%) survivors from the prospective COVID MECH study, underwent CMR median 175 [IQR 105-217] days after COVID-19 hospitalization. Abnormal CMR was defined as left ventricular ejection fraction (LVEF) <50% or myocardial scar by late gadolinium enhancement. CMR indices were compared to healthy controls (n = 32), and to circulating biomarkers measured during the index hospitalization.
Results
Abnormal CMR was present in 12 (21%) patients, of whom 3 were classified with major pathology (scar and LVEF <50% or LVEF <40%). There was no difference in the need of mechanical ventilation, length of hospital stay, and vital signs between patients with vs without abnormal CMR after 6 months. Severe acute respiratory syndrome coronavirus 2 viremia and concentrations of inflammatory biomarkers during the index hospitalization were not associated with persistent CMR pathology. Cardiac troponin T and N-terminal pro-B-type natriuretic peptide concentrations on admission, were higher in patients with CMR pathology, but these associations were not significant after adjusting for demographics and established cardiovascular disease.
Conclusions
CMR pathology 6 months after moderate-to-severe COVID-19 was present in 21% of patients and did not correlate with severity of the disease. Cardiovascular biomarkers during COVID-19 were higher in patients with CMR pathology, but with no significant association after adjusting for confounders.
Trial registration
COVID MECH Study ClinicalTrials.gov Identifier: NCT04314232.

Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

Am Heart J: 12 Aug 2021; 242:61-70
Myhre PL, Heck SL, Skranes JB, Prebensen C, ... Lyngbakken MN, Omland T
Am Heart J: 12 Aug 2021; 242:61-70 | PMID: 34400140
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Abstract

Cardiovascular risk and outcomes in symptomatic patients with suspected coronary artery disease and non coronary vascular disease: A report from the PROMISE trial.

Vemulapalli S, Stebbins A, Jones WS, Gutierrez JA, ... Hoffmann U, Douglas PS
Background
Non-coronary vascular disease (NCVD) is associated with adverse cardiovascular events. Little is known about physician risk assessment, prevalence of coronary artery disease (CAD), cardiac catheterization, and the performance of the atherosclerotic cardiovascular disease (ASCVD) risk score in patients with NCVD.
Methods
Retrospective analysis of outpatients with angina and no known CAD from the PROMISE trial. NCVD included carotid artery stenosis ≥50%, or history of stroke or peripheral artery disease. Multivariable models of physician estimates of the probability of obstructive CAD, prevalence of non-obstructive and obstructive CAD, referral to cardiac catheterization, and all-cause death/myocardial infarction/unstable angina were performed.
Results
Among 10,001 patients in the PROMISE trial, 379 (3.8%) patients had NCVD. Only 8.5% of participants with NCVD were categorized as high-risk for obstructive CAD by physicians, though 15.5% (25/161) had obstructive CAD in those randomized to coronary computed tomography (CTA). NCVD was independently associated with non-obstructive (aOR = 1.58; 95% CI 1.18-2.61; P = .006) but not obstructive CAD by CTA. Adjusted referral to cardiac catheterization was similar with and without NCVD (aOR 1.04; 95% CI 0.88-1.94, P = .19). NCVD was associated with an increased risk of all-cause death/MI/UA (aOR 2.03; 95% CI 1.37-3.01, P < .001). There was no interaction between NCVD status and ASCVD risk score.
Conclusions
Among patients with NCVD and angina, NCVD had increased adjusted risks of CAD and adverse outcomes which were not well described by ASCVD risk score and were underrecognized by physicians. Increased awareness and better risk stratification tools for patients with NCVD may be necessary to recognize the associated CV risk and optimize diagnostic testing and therapies.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 08 Aug 2021; 242:82-91
Vemulapalli S, Stebbins A, Jones WS, Gutierrez JA, ... Hoffmann U, Douglas PS
Am Heart J: 08 Aug 2021; 242:82-91 | PMID: 34384742
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Abstract

Younger patients with chronic limb threatening ischemia face more frequent amputations.

Weissler EH, Ford CB, Patel MR, Goodney P, ... Long C, Jones WS
Introduction
Amputations among younger patients with chronic limb threatening ischemia (CLTI) may carry higher personal and societal costs, but younger patients are often not included in CLTI research because of dataset limitations. We aimed to characterize and compare outcomes between younger (<65 years old) and older patients with CLTI.
Methods
This retrospective cohort study identified patients with CLTI between July 1, 2014 and December 31, 2017 in the MarketScan commercial claims database, a proprietary set of claims for over 50 million patients with private insurance in the United States. The primary outcome was major adverse limb events (MALE); secondary outcomes included amputations, major adverse cardiovascular events, and statin prescription fills.
Results
The study cohort included 64,663 people with CLTI, of whom 25,595 (39.6%) were <65 years old. Younger patients were more likely to have diabetes mellitus (54.1% versus 49.9%, P<.001) but less likely to have other comorbidities. A higher proportion of younger patients suffered MALE (31.7% versus 30.2%, P=.002), specifically amputation (11.5% versus 9.3%, P<.001). After adjustment, age <65 years old was associated with a 24% increased risk of amputation (HRadj 1.24, 95%CI 1.18-1.32, P<.001) and a 10% increased risk of MALE (HRadj 1.10, 95%CI 1.07-1.14, P<.001).
Conclusions
A significant proportion of commercially insured patients with CLTI are under the age of 65, and younger patients have worse limb-related outcomes. These findings highlight the importance of aggressively treating risk factors for atherosclerosis and intentionally including younger patients with CLTI in future analyses to better understand their disease patterns and outcomes.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 07 Aug 2021; 242:6-14
Weissler EH, Ford CB, Patel MR, Goodney P, ... Long C, Jones WS
Am Heart J: 07 Aug 2021; 242:6-14 | PMID: 34371002
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This program is still in alpha version.