Journal: Am Heart J

Sorted by: date / 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: 30 Aug 2021; 239:59-63
Barbery CE, Giczewska A, White J, Lokhnygina Y, ... Hernandez AF, Jones WS
Am Heart J: 30 Aug 2021; 239:59-63 | PMID: 33905751
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Abstract

The impact of a population-based prevention program on cardiovascular events: Findings from the heart of new Ulm project.

Sidebottom AC, Miedema MD, Benson G, Vacquier M, ... Boucher JL, Bradley SM
Background
Cardiovascular disease (CVD) and its associated risk factors are the principal drivers of mortality and healthcare costs in the United States with rural residents experiencing higher CVD death rates than their urban counterparts.
Methods
The purpose of this study was to examine incidence of major CVD events over 9 years of implementation of the Heart of New Ulm (HONU) Project, a rural population-based CVD prevention initiative. HONU interventions were delivered at individual, organizational, and community levels addressing clinical risk factors, lifestyle behaviors and environmental changes. The sample included 4,056 residents of New Ulm matched with 4,056 residents from a different community served by the same health system. The primary outcome was a composite of major CVD events (myocardial infarction, ischemic stroke, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), and CVD-related death). Secondary outcomes were the individual CVD events and procedures.
Results
The proportion of residents in New Ulm with a major CVD event (7.79%) was not significantly different than the comparison community (8.43%, P = .290). However, the total number of events did differ by community with fewer events in New Ulm than the comparison community (447 vs 530, P = .005), with 48 fewer strokes (84 vs 132, P = .001) and 42 fewer PCI procedures (147 vs 189, P = 0.019) in New Ulm. Incidence of ischemic stroke was lower in the New Ulm community (1.85 vs 2.61, P = .020) than in the comparison community. Other specific CVD events did not have significantly different incidence or frequencies between the 2 communities.
Conclusion
In HONU, the proportion of residents experiencing a CVD event was not significantly lower than a match comparison community. However, there was a significant reduction in the total number of CVD events in New Ulm, driven primarily by lower stroke, PCI, and CABG events in the intervention community.

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

Am Heart J: 30 Aug 2021; 239:38-51
Sidebottom AC, Miedema MD, Benson G, Vacquier M, ... Boucher JL, Bradley SM
Am Heart J: 30 Aug 2021; 239:38-51 | PMID: 33957104
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Abstract

Sarcopenia in cardiac surgery: Dual X-ray absorptiometry study from the McGill frailty registry.

Joshi A, Mancini R, Probst S, Abikhzer G, ... Rudski LG, Afilalo J
Background
To determine the prevalence and prognostic value of sarcopenia measured by dual x-ray absorptiometry (DXA) and physical performance tests in patients undergoing coronary artery bypass surgery or heart valve procedures.
Methods
Adults undergoing cardiac surgery were prospectively enrolled and completed a questionnaire, physical performance battery, and a DXA scan (GE Lunar) to measure appendicular muscle mass indexed to height2 (AMMI). Patients were categorized as sarcopenic based on European Working Group 2 guidelines if they had low AMMI defined as <7 kg/m2 for men or <5.5 kg/m2 for women, and low muscle strength defined as 5 chair rise time ≥15 seconds. Cox proportional hazards regression was used to test the association between sarcopenia and all-cause mortality over a median follow-up of 4.3 years.
Results
The cohort consisted of 141 patients with a mean age of 69.7 ± 10.0 years and 21% females. The prevalence rates of low AMMI, slow chair rise time, and sarcopenia (low AMMI and slow chair rise time) were 24%, 57%, 13%, respectively. The 4-year survival rate was 79% in the non-sarcopenic group as compared to 56% in the sarcopenic group (Log-rank P = 0.01). In the multivariable model, each standard deviation of decreasing AMMI and increasing chair rise time was associated with a hazard ratio for all-cause mortality of 1.84 (95% CI 1.18, 2.86) and 1.79 (95% CI 1.26, 2.54), respectively.
Conclusion
Lower-extremity muscle strength and DXA-based muscle mass are objective indicators of sarcopenia that are independently predictive of all-cause mortality in older cardiac surgery patients.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Aug 2021; 239:52-58
Joshi A, Mancini R, Probst S, Abikhzer G, ... Rudski LG, Afilalo J
Am Heart J: 30 Aug 2021; 239:52-58 | PMID: 33957101
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Abstract

Depressive hypertension: A proposed human endotype of brain/gut microbiome dysbiosis.

Stevens BR, Pepine CJ, Richards EM, Kim S, Raizada MK
Background
Hypertension (HTN) is frequently linked with depression (DEP) in adults with cardiovascular disease (CVD), yet the underlying mechanism and successful management remain elusive. We approached this knowledge gap through the lens that humans are eukaryote-prokaryote \"meta-organisms,\" such that cardiovascular disease dysregulation is a mosaic disorder involving dysbiosis of the gut. We hypothesized that patients diagnosed with hypertension plus depression harbor a unique gut microbial ecology with attending functional genomics engaged with their hosts\' gut/brain axis physiology.
Methods
Stool microbiome DNA was analyzed by whole metagenome shotgun sequencing in 54 subjects parsed into cohorts diagnosed with HTN only (N = 18), DEP only (N = 7), DEP plus HTN (DEP-HTN) (N = 8), or reference subjects with neither HTN nor DEP (N = 21). A novel battery of machine-learning multivariate analyses of de-noised data yielded effect sizes and permutational covariance-based dissimilarities that significantly differentiated the cohorts (false discovery rate (FDR)-adjusted P ≤ .05); data clustering within 95% confidence interval).
Results
Metagenomic significant differences extricated the four cohorts. Data of the cohort exhibiting DEP-HTN were germane to the interplay of central control of blood pressure concomitant with the neuropathology of depressive disorders. DEP-HTN gut bacterial community ecology was defined by co-occurrence of Eubacterium siraeum, Alistipes obesi, Holdemania filiformis, and Lachnospiraceae bacterium 1.1.57FAA with Streptococcus salivariu. The corresponding microbial functional genomics of DEP-HTN engaged pathways degrading GABA and beneficial short chain fatty acids (SCFA), and are associated with enhanced sodium absorption and inflammasome induction.
Conclusions
These data suggest a new putative endotype of hypertension, which we denote \"depressive-hypertension\" (DEP-HTN), for which we posit a model that is distinctive from either HTN alone or DEP alone. An \"endotype\" is a subtype of a heterogeneous pathophysiological mechanism. The DEP-HTN model incorporates a unique signature of microbial taxa and functional genomics with crosstalk that putatively intertwines host pathophysiology involving the gastrointestinal tract with disruptions in central control of blood pressure and mood. The DEP-HTN endotype model engages cardiology with gastroenterology and psychiatry, providing a proof-of-concept foundation to explore future treatments, diagnosis, and prevention of HTN-coupled mood disorders.

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

Am Heart J: 30 Aug 2021; 239:27-37
Stevens BR, Pepine CJ, Richards EM, Kim S, Raizada MK
Am Heart J: 30 Aug 2021; 239:27-37 | PMID: 33984318
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Abstract

Advanced heart failure patients supported with ambulatory inotropic therapy: What defines success of therapy?

Grubb CS, Truby LK, Topkara VK, Bohnen MS, ... Naka Y, Farr M
Objective
The objective of this study was to describe the profiles and outcomes of a cohort of advanced heart failure patients on ambulatory inotropic therapy (AIT).
Background
With the growing burden of patients with end-stage heart failure, AIT is an increasingly common short or long-term option, for use as bridge to heart transplant (BTT), bridge to ventricular assist device (BTVAD), bridge to decision regarding advanced therapies (BTD) or as palliative care. AIT may be preferred by some patients and physicians to facilitate hospital discharge. However, counseling patients on risks and benefits is critically important in the modern era of defibrillators, durable mechanical support and palliative care.
Methods
We retrospectively studied a cohort of 241 patients on AIT. End points included transplant, VAD implantation, weaning of inotropes, or death. The primary outcomes were survival on AIT and ability to reach intended goal if planned as BTT or BTVAD. We also evaluated recurrent heart failure hospitalizations, incidence of ventricular arrhythmias (VT/VF) and indwelling line infections. Unintended consequences of AIT, such reaching unintended end point (e.g. VAD implantation in BTT patient) or worse than expected outcome after LVAD or HT, were recorded.
Results
Mean age of the cohort was 60.7 ± 13.2 years, 71% male, with Class III-IV heart failure (56% non-ischemic). Average ejection fraction was 19.4 ± 10.2%, pre-AIT cardiac index was 1.5 ± 0.4 L/min/m2 and 24% had prior ventricular arrhythmias. Overall on-AIT 1-year survival was 83%. Hospitalizations occurred in 51.9% (125) of patients a total of 174 times for worsening heart failure, line complication or ventricular arrhythmia. In the BTT cohort, only 42% were transplanted by the end of follow-up, with a 14.8% risk of death or delisting for clinical deterioration. For the patients who were transplanted, 1-year post HT survival was 96.7%. In the BTVAD cohort, 1-year survival after LVAD was 90%, but with 61.7% of patients undergoing LVAD as INTERMACS 1-2. In the palliative care cohort, only 24.5% of patients had a formal palliative care consult prior to AIT.
Conclusions
AIT is a strategy to discharge advanced heart failure patients from the hospital. It may be useful as bridge to transplant or ventricular assist device, but may be limited by complications such as hospitalizations, infections, and ventricular arrhythmias. Of particular note, it appears more challenging to bridge to transplant on AIT in the new allocation system. It is important to clarify the goals of AIT therapy upfront and continue to counsel patients on risks and benefits of the therapy itself and potential unintended consequences. Formalized, multi-disciplinary care planning is essential to clearly define individualized patient, as well as programmatic goals of AIT.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Aug 2021; 239:11-18
Grubb CS, Truby LK, Topkara VK, Bohnen MS, ... Naka Y, Farr M
Am Heart J: 30 Aug 2021; 239:11-18 | PMID: 33984317
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Abstract

A prospective multicenter validation study for a novel angiography-derived physiological assessment software: Rationale and design of the radiographic imaging validation and evaluation for Angio-iFR (ReVEAL iFR) study.

Ono M, Serruys PW, Patel MR, Escaned J, ... Inderbitzen B, Onuma Y
Angiography-derived physiological assessment of coronary lesions has emerged as an alternative to wire-based assessment aiming at less-invasiveness and shorter procedural time as well as cost effectiveness in physiology-guided decision making. However, current available image-derived physiology software have limitations including the requirement of multiple projections and are time consuming. METHODS/
Design:
The ReVEAL iFR (Radiographic imaging Validation and EvALuation for Angio-iFR) trial is a multicenter, multicontinental, validation study which aims to validate the diagnostic accuracy of the Angio-iFR medical software device (Philips, San Diego, US) in patients undergoing angiography for Chronic Coronary Syndrome (CCS). The Angio-iFR will enable operators to predict both the iFR and FFR value within a few seconds from a single projection of cine angiography by using a lumped parameter fluid dynamics model. Approximately 440 patients with at least one de-novo 40% to 90% stenosis by visual angiographic assessment will be enrolled in the study. The primary endpoint is the sensitivity and specificity of the iFR and FFR for a given lesion compared to the corresponding invasive measures. The enrollment started in August 2019, and was completed in March 2021. SUMMARY: The Angio-iFR system has the potential of simplifying physiological evaluation of coronary stenosis compared with available systems, providing estimates of both FFR and iFR. The ReVEAL iFR study will investigate the predictive performance of the novel Angio-iFR software in CCS patients. Ultimately, based on its unique characteristics, the Angio-iFR system may contribute to improve adoption of functional coronary assessment and the workflow in the catheter laboratory.


Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Aug 2021; 239:19-26
Ono M, Serruys PW, Patel MR, Escaned J, ... Inderbitzen B, Onuma Y
Am Heart J: 30 Aug 2021; 239:19-26 | PMID: 33992606
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Abstract

Sacubitril/valsartan versus enalapril on exercise capacity in patients with heart failure with reduced ejection fraction: A randomized, double-blind, active-controlled study.

Dos Santos MR, Alves MNN, Jordão CP, Pinto CEN, ... Negrão CE, Barretto ACP
Sacubitril/valsartan reduces mortality in patients with heart failure with reduced ejection fraction (HFrEF) when compared with enalapril. However, it is unknown the effect of both treatments on exercise capacity. We compared sacubitril/valsartan versus enalapril in patients with HFrEF based on peak oxygen consumption (VO2) and 6-minute walk test (6-MWT).
Methods
We included 52 participants with HFrEF with a left ventricular ejection fraction <40% to receive either sacubitril/valsartan (target dose of 400 mg daily) or enalapril (target dose of 40 mg daily). Peak VO2 was measured by using cardiopulmonary exercise testing. Six-minute walk test was also performed.
Results
At 12 weeks, the sacubitril/valsartan (mean dose 382.6 ± 57.6 mg daily) group had increased peak VO2 of 13.1% (19.35 ± 0.99 to 21.89 ± 1.04 mL/kg/min) and enalapril (mean dose 34.4 ± 9.2 mg daily) 5.6% (18.58 ± 1.19 to 19.62 ± 1.25 mL/kg/min). However, no difference was found between groups (P = .332 interaction). At 24 weeks, peak VO2 increased 13.5% (19.35 ± 0.99 to 21.96 ± 0.98 mL/kg/min) and 12.0% (18.58 ± 1.19 to 20.82 ± 1.18 mL/kg/min) in sacubitril/valsartan (mean dose 400 ± 0 mg daily) and enalapril (mean dose 32.7 ± 11.0 mg daily), respectively. However, no differences were found between groups (P= .332 interaction). At 12 weeks, 6-MWT increased in both groups (sacubitril/valsartan: 459 ± 18 to 488 ± 17 meters [6.3%] and enalapril: 443 ± 22 to 477 ± 21 meters [7.7%]). At 24 weeks, sacubitril/valsartan increased 18.3% from baseline (543 ± 26 meters) and enalapril decreased slightly to 6.8% (473 ± 31 meters), but no differences existed between groups (P= .257 interaction).
Conclusions
Compared to enalapril, sacubitril/valsartan did not substantially improve peak VO2 or 6-MWT after 12 or 24 weeks in participants with HFrEF. (NEPRIExTol-HF Trial, ClinicalTrials.gov number, NCT03190304).

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Aug 2021; 239:1-10
Dos Santos MR, Alves MNN, Jordão CP, Pinto CEN, ... Negrão CE, Barretto ACP
Am Heart J: 30 Aug 2021; 239:1-10 | PMID: 33992607
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Abstract

Rationale and design of the intravenous iron for treatment of anemia before cardiac surgery trial.

Myles PS, Richards T, Klein A, Smith J, ... Wallace S, ANZCA Clinical Trials Network

Background:
Approximately 20% to 30% of patients awaiting cardiac surgery are anemic. Anemia increases the likelihood of requiring a red cell transfusion and is associated with increased complications, intensive care, and hospital stay following surgery. Iron deficiency is the commonest cause of anemia and preoperative intravenous (IV) iron therapy thus may improve anemia and therefore patient outcome following cardiac surgery. We have initiated the intravenous iron for treatment of anemia before cardiac surgery (ITACS) Trial to test the hypothesis that in patients with anemia awaiting elective cardiac surgery, IV iron will reduce complications, and facilitate recovery after surgery. Methods ITACS is a 1,000 patient, international randomized trial in patients with anemia undergoing elective cardiac surgery. The patients, health care providers, data collectors, and statistician are blinded to whether patients receive IV iron 1,000 mg, or placebo, at 1-26 weeks before their planned date of surgery. The primary endpoint is the number of days alive and at home up to 90 days after surgery. Results To date, ITACS has enrolled 615 patients in 30 hospitals in 9 countries. Patient mean (SD) age is 66 (12) years, 63% are male, with a mean (SD) hemoglobin at baseline of 118 (12) g/L; 40% have evidence (ferritin <100 ng/mL and/or transferrin saturation <25%) suggestive of iron deficiency. Most (59%) patients have undergone coronary artery surgery with or without valve surgery.
Conclusions:
The ITACS Trial will be the largest study yet conducted to ascertain the benefits and risks of IV iron administration in anemic patients awaiting cardiac surgery.


Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Aug 2021; 239:64-72
Myles PS, Richards T, Klein A, Smith J, ... Wallace S, ANZCA Clinical Trials Network
Am Heart J: 30 Aug 2021; 239:64-72 | PMID: 34033804
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Abstract

Batch enrollment for an artificial intelligence-guided intervention to lower neurologic events in patients with undiagnosed atrial fibrillation: rationale and design of a digital clinical trial.

Yao X, Attia ZI, Behnken EM, Walvatne K, ... Friedman PA, Noseworthy PA
Background
Clinical trials are a fundamental tool to evaluate medical interventions but are time-consuming and resource-intensive.
Objectives
To build infrastructure for digital trials to improve efficiency and generalizability and test it using a study to validate an artificial intelligence algorithm to detect atrial fibrillation (AF).
Design
We will prospectively enroll 1,000 patients who underwent an electrocardiogram for any clinical reason in routine practice, do not have a previous diagnosis of AF or atrial flutter and would be eligible for anticoagulation if AF is detected. Eligible patients will be identified using digital phenotyping algorithms, including natural language processing that runs on the electronic health records. Study invitations will be sent in batches via patient portal or letter, which will direct patients to a website to verify eligibility, learn about the study (including video-based informed consent), and consent electronically. The method aims to enroll participants representative of the general patient population, rather than a convenience sample of patients presenting to clinic. A device will be mailed to patients to continuously monitor for up to 30 days. The primary outcome is AF diagnosis and burden; secondary outcomes include patients\' experience with the trial conduct methods and the monitoring device. The enrollment, intervention, and follow-up will be conducted remotely, ie, a patient-centered site-less trial.
Summary
This is among the first wave of trials to adopt digital technologies, artificial intelligence, and other pragmatic features to create efficiencies, which will pave the way for future trials in a broad range of disease and treatment areas. Clinicaltrials.gov: NCT04208971.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Aug 2021; 239:73-79
Yao X, Attia ZI, Behnken EM, Walvatne K, ... Friedman PA, Noseworthy PA
Am Heart J: 30 Aug 2021; 239:73-79 | PMID: 34033803
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Abstract

Study design and rationale of VALOR-HCM: evaluation of mavacamten in adults with symptomatic obstructive hypertrophic cardiomyopathy who are eligible for septal reduction therapy.

Desai MY, Wolski K, Owens A, Naidu SS, ... Sehnert AJ, Nissen SE
Background
Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder which frequently leads to symptoms such as dyspnea and exercise intolerance, often due to severe dynamic left ventricular outflow tract obstruction (LVOTO). Current guideline-recommended pharmacotherapies have variable therapeutic responses to relieve LVOTO. In recent phases 2 and 3, clinical trials for symptomatic obstructive HCM (oHCM), mavacamten, a small molecule inhibitor of β-cardiac myosin has been shown to improve symptoms, exercise capacity, health status, reduce LVOTO, along with having a beneficial impact on cardiac structure and function.
Methods
VALOR-HCM is designed as a multicenter (approximately 20 centers in United States) phase 3, double-blind, placebo-controlled, randomized study. The study population consists of approximately 100 patients (≥18 years old) with symptomatic oHCM who meet 2011 American College of Cardiology/American Heart Association and/or 2014 European Society of Cardiology HCM-guideline criteria and are eligible and willing to undergo septal reduction therapy (SRT). The study duration will be up to 138 weeks, including an initial 2-week screening period, followed by16 weeks of placebo-controlled treatment, 16 weeks of active blinded treatment, 96 weeks of long-term extension, and an 8-week posttreatment follow-up visit. The primary endpoint will be a composite of the decision to proceed with SRT prior to or at Week 16 or remain guideline eligible for SRT at Week 16. Secondary efficacy endpoints will include change (from baseline to Week 16 in the mavacamten group vs placebo) in postexercise LVOT gradient, New York Heart Association class, Kansas City Cardiomyopathy Questionnaire clinical summary score, NT-proBNP, and cardiac troponin. Exploratory endpoints aim to characterize the effect of mavacamten on multiple aspects of oHCM pathophysiology.
Conclusions
In severely symptomatic drug-refractory oHCM patients meeting guideline criteria of eligibility for SRT, VALOR-HCM will primarily study if a 16-week course of mavacamten reduces or obviates the need for SRT using clinically driven endpoints.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Aug 2021; 239:80-89
Desai MY, Wolski K, Owens A, Naidu SS, ... Sehnert AJ, Nissen SE
Am Heart J: 30 Aug 2021; 239:80-89 | PMID: 34038706
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Abstract

Pre-operative atrial fibrillation and early right ventricular failure after left ventricular assist device implantation: a systematic review and meta-analysis.

Kittipibul V, Blumer V, Hernandez GA, Fudim M, ... Chaparro S, Agarwal R
Background
Right ventricular failure (RVF) remains a major cause of morbidity and mortality after left ventricular assist device (LVAD). Atrial fibrillation (AF) is known for its deleterious effects on cardiac function and hemodynamics. The association of pre-operative AF with the risk of early post-LVAD RVF has not been well described.
Method
A comprehensive literature search was performed through April, 9 2021. Cohort studies comparing the risk of post-operative RVF and/or need for right ventricular assist device (RVAD) after LVAD in patients with or without AF were included. Pooled odds ratio (OR) with 95% confidence intervals (CI) and I2 statistic were calculated using the random-effects model.
Results
Six studies were included in the analysis. Post-operative RVF was reported in 5 studies (1,841 patients) and RVAD use was reported in 4 studies (1,355 patients). There is a non-significant trend toward a higher risk of post-operative RVF in the AF group (pooled OR=1.25, 95%CI=0.99-1.58). No significant association between AF and RVAD use is noted (pooled OR=1.17, 95%CI=0.82-1.66).
Conclusions
Pre-operative AF is not significantly associated with higher risks of post-operative RVF and RVAD use after LVAD implantation, although the trend toward higher post-operative RVF is observed in patients with pre-operative AF. Additional research using a larger study population is warranted to better understand the association of pre-operative AF and the development of post-LVAD RVF.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Aug 2021; 239:120-128
Kittipibul V, Blumer V, Hernandez GA, Fudim M, ... Chaparro S, Agarwal R
Am Heart J: 30 Aug 2021; 239:120-128 | PMID: 34038705
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Abstract

Simplifying the ISCHEMIA trial algorithm for clinical practice: Identifying left main coronary artery disease using coronary artery calcium scans.

Money JE, Muhlestein JB, Mason S, Bair TL, ... Horne BD, Anderson JL
Background
Several recent trials have evaluated invasive versus medical therapy for stable ischemic heart disease. Importantly, patients with significant left main coronary stenosis (LMCS) were excluded from these trials. In the ISCHEMIA trial, these patients were identified by a coronary CT angiogram (CCTA), which adds time, expense, and contrast exposure. We tested whether a coronary artery calcium scan (CACS), a simpler, less expensive test, could replace CCTA to exclude significant LMCS.
Methods
We hypothesized that patients with ≥50% LMCS would have a LM CACS score > 0. As a corollary, we postulated that a LM CACS = 0 would exclude patients with LMCS. To test this, we searched Intermountain Healthcare\'s electronic medical records database for all adult patients who had undergone non-contrast cardiac CT for quantitative CACS scoring prior to invasive coronary angiography (ICA). Patients aged <50 and those with a heart transplant were excluded. Cases with incomplete (qualitative) angiographic reports for LMCS and those with incomplete or discrepant LM CACS results were reviewed and reassessed blinded to CACS or ICA findings, respectively.
Results
Among 669 candidate patients with CACS followed by ICA, 36 qualifying patients were identified who had a quantitative CACS score and LMCS ≥ 50%. Their age averaged 71.8 years, and 81% were men. Angiographic LMCS averaged 72% (range 50%-99%). Median time between CACS and ICA was 6 days. Total CACS score averaged 2,383 Agatston Units (AU), range 571-6,636. LM CACS score averaged 197 AU, range 31-610. Importantly, no LMCS patient had a LM CACS score of 0 vs 57% (362/633) of non-LMCS controls (P < .00001).
Conclusions
Our results support the hypothesis that an easily administered, inexpensive, low radiation CACS can identify a large subset of patients with a very low risk of LMCS who would not have the need for routine CCTA. Using CACS to exclude LMCS may efficiently allow for safe implementation of an initial medical therapy strategy of patients with stable ischemic heart disease in clinical practice. These promising results deserve validation in larger data sets.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Aug 2021; 239:129-134
Money JE, Muhlestein JB, Mason S, Bair TL, ... Horne BD, Anderson JL
Am Heart J: 30 Aug 2021; 239:129-134 | PMID: 34051172
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Impact:
Abstract

Potential impact of the steroid hormone, vitamin D, on the vasculature.

Tintut Y, Demer LL
The role of vitamin D in the cardiovascular system is complex because it regulates expression of genes involved in diverse metabolic processes. Although referred to as a vitamin, it is more accurately considered a steroid hormone, because it is produced endogenously in the presence of ultraviolet light. It occurs as a series of sequentially activated forms, here referred to as vitamin D-hormones. A little-known phenomenon, based on pre-clinical data, is that its biodistribution and potential effects on vascular disease likely depend on whether it is derived from diet or sunlight. Diet-derived vitamin D-hormones are carried in the blood, at least in part, in chylomicrons and lipoprotein particles, including low-density lipoprotein. Since low-density lipoprotein is known to accumulate in the artery wall and atherosclerotic plaque, diet-derived vitamin D-hormones may also collect there, and possibly promote the osteochondrogenic mineralization associated with plaque. Also, little known is the fact that the body stores vitamin D-hormones in adipose tissue with a half-life on the order of months, raising doubts about whether the use of the term \"daily requirement\" is appropriate. Cardiovascular effects of vitamin D-hormones are controversial, and risk appears to increase with both low and high blood levels. Since low serum vitamin D-hormone concentration is reportedly associated with increased cardiovascular and orthopedic risk, oral supplementation is widely used, often together with calcium supplements. However, meta-analyses show that oral vitamin D-hormone supplementation does not protect against cardiovascular events, findings that are also supported by a randomized controlled trial. These considerations suggest that prevalent recommendations for vitamin D-hormone supplementation for the purpose of cardiovascular protection should be carefully reconsidered.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Aug 2021; 239:147-153
Tintut Y, Demer LL
Am Heart J: 30 Aug 2021; 239:147-153 | PMID: 34051171
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Impact:
Abstract

The association of healthcare disparities and patient-specific factors on clinical outcomes in peripheral artery disease.

Narcisse DI, Ford CB, Weissler EH, Lippmann SJ, ... Patel MR, Jones WS
Background
PAD increases the risk of cardiovascular mortality and limb loss, and disparities in treatment and outcomes have been described. However, the association of patient-specific characteristics with variation in outcomes is less well known.
Methods
Patients with PAD from Duke University Health System (DUHS) between January 1, 2015 and March 31, 2016 were identified. PAD status was confirmed through ground truth adjudication and predictive modeling using diagnosis codes, procedure codes, and other administrative data. Symptom severity, lower extremity imaging, and ankle-brachial index (ABI) were manually abstracted from the electronic health record (EHR). Data was linked to Centers for Medicare and Medicaid Services data to provide longitudinal follow up. Primary outcome was major adverse vascular events (MAVE), a composite of all-cause mortality, myocardial infarction (MI), stroke, lower extremity revascularization and amputation.
Results
Of 1,768 patients with PAD, 31.6% were asymptomatic, 41.2% had intermittent claudication (IC), and 27.3% had chronic limb-threatening ischemia (CLTI). At 1 year, patients with CLTI had higher rates of MAVE compared with asymptomatic or IC patients. CLTI and Medicaid dual eligibility were independent predictors of mortality. CLTI and Black race were associated with amputation.
Conclusions
Rates of MAVE were highest in patients with CLTI, but patients with IC or asymptomatic disease also had high rates of adverse events. Black and Medicaid dual-eligible patients were disproportionately present in the CLTI subgroup and were at higher risk of amputation and mortality, respectively. Future studies must focus on early identification of high-risk patient groups to improve outcomes in patients with PAD.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Aug 2021; 239:135-146
Narcisse DI, Ford CB, Weissler EH, Lippmann SJ, ... Patel MR, Jones WS
Am Heart J: 30 Aug 2021; 239:135-146 | PMID: 34052213
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Impact:
Abstract

Early diuretic strategies and the association with In-hospital and Post-discharge outcomes in acute heart failure.

Fudim M, Spates T, Sun JL, Kittipibul V, ... O\'Connor CM, Mentz RJ
Background
Decongestion is a primary goal during hospitalizations for decompensated heart failure (HF). However, data surrounding the preferred route and strategy of diuretic administration are limited with varying results in prior studies.
Methods
This is a retrospective analysis using patients from ASCEND-HF with a stable diuretic strategy in the first 24 hours following randomization. Patients were divided into three groups: intravenous (IV) continuous, IV bolus and oral strategy. Baseline characteristics, in-hospital outcomes, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality were compared across groups. Inverse propensity weighted modeling was used for adjustment.
Results
Among 5,738 patients with a stable diuretic regimen in the first 24 hours (80% of overall ASCEND trial), 3,944 (68.7%) patients received IV intermittent bolus administration of diuretics, 799 (13.9%) patients received IV continuous therapy and 995 (17.3%) patients with oral administration. Patients in the IV continuous group had a higher baseline creatinine (IV continuous 1.4 [1.1-1.7]; intermittent bolus 1.2 [1.0-1.6]; oral 1.2 [1.0-1.4] mg/dL; P <0.001) and high NTproBNP (IV continuous 5,216 [2,599-11,603]; intermittent bolus 4,944 [2,339-9,970]; oral 3,344 [1,570-7,077] pg/mL; P <0.001). There was no difference between IV continuous and intermittent bolus group in weight change, total urine output and change in renal function till 10 days/discharge (adjusted P >0.05 for all). There was no difference in 30 day mortality and HF readmission (adjusted OR 1.08 [95%CI: 0.74, 1.57]; P = 0.701) and 180 days mortality (adjusted OR 1.04 [95%CI: 0.75, 1.43]; P = 0.832).
Conclusion
In a large cohort of patients with decompensated HF, there were no significant differences in diuretic-related in-hospital, or post-discharge outcomes between IV continuous and intermittent bolus administration. Tailoring appropriate diuretic strategy to different states of acute HF and congestion phenotypes needs to be further investigated.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Aug 2021; 239:110-119
Fudim M, Spates T, Sun JL, Kittipibul V, ... O'Connor CM, Mentz RJ
Am Heart J: 30 Aug 2021; 239:110-119 | PMID: 34052212
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Impact:
Abstract

Catheter-based alcohol-mediated renal denervation for the treatment of uncontrolled hypertension: design of two sham-controlled, randomized, blinded trials in the absence (TARGET BP OFF-MED) and presence (TARGET BP I) of antihypertensive medications.

Mahfoud F, Weber M, Schmieder RE, Lobo MD, ... Pathak A, Kandzari DE
Background
Arterial hypertension is a common and life-threatening condition and poses a large global health burden. Device-based treatments have been developed as adjunctive or alternative therapy, to be used with or without antihypertensive medication for treating uncontrolled hypertension. The safety and feasibility of chemical renal denervation (RDN) using the Peregrine Catheter and alcohol were demonstrated in a first-in-man and open-label clinical trials, prompting the initiation of the ongoing TARGET BP OFF-MED and TARGET BP I trials.
Design
The TARGET BP trials are randomized, blinded, sham-controlled trials designed to assess the safety and efficacy of alcohol-mediated RDN for the treatment of uncontrolled hypertension in the absence of antihypertensive medications (TARGET BP OFF-MED) or in addition to prescribed antihypertensive medications (TARGET BP I). Subjects with confirmed uncontrolled hypertension and suitable renal artery anatomy are randomized (1:1) to receive either RDN using the Peregrine Kit with alcohol (0.6 mL per renal artery) infused through the Peregrine Catheter or diagnostic renal angiography only (sham procedure). TARGET BP OFF-MED completed enrollment and randomized 96 subjects. TARGET BP I will randomize approximately 300 subjects and will transition to an open-label safety cohort of approximately 300 subjects receiving RDN once the primary efficacy endpoint of the Randomized Controlled Trial (RCT) cohort has been met. Primary endpoints are change in mean 24-hour ambulatory systolic blood pressure from baseline to 8 weeks (TARGET BP OFF-MED) and 3 months (TARGET BP I) post-procedure.
Conclusion
The TARGET BP trials are the first large-scale, international, randomized trials aimed to investigate the safety and BP lowering efficacy of a novel RDN method, with perivascular alcohol delivery using the Peregrine Kit.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Aug 2021; 239:90-99
Mahfoud F, Weber M, Schmieder RE, Lobo MD, ... Pathak A, Kandzari DE
Am Heart J: 30 Aug 2021; 239:90-99 | PMID: 34052211
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Impact:
Abstract

Estimating the real-world performance of the PROMISE minimal-risk tool.

Nanna MG, Wang TY, Chiswell K, Sun JL, ... Fordyce CB, Douglas PS
Background
Stable chest pain is a common indication for cardiac catheterization. We assessed the prognostic value of the Prospective Multicenter Imaging Study for Evaluation (PROMISE) Minimal-Risk Tool in identifying patients who are at very low risk of obstructive coronary artery disease (CAD) or downstream cardiovascular adverse outcomes.
Methods
We applied the PROMISE Minimal-Risk Tool to consecutive patients without known CAD who underwent elective cardiac catheterization for stable angina from January 1, 2000 to December 31, 2014 in the Duke Databank for Cardiovascular Disease (DDCD). Patients with scores >0.46 (top decile of lowest-risk from the PROMISE cohort) were classified as low-risk. Logistic regression modeling compared likelihood of freedom from obstructive coronary artery disease on index angiography, 2-year survival, and 2-year survival free of myocardial infarction (MI) and MI/revascularization between low- and non low-risk patients. Alternative cut points to define low- risk patients were also explored.
Results
Among 6251 patients undergoing cardiac catheterization for stable chest pain, 1082 (17.3%) were low-risk per the PROMISE minimal-risk tool. Among low risk patients, obstructive coronary artery disease was observed in 14.9% and left main disease (≥ 50% Stenosis) was rare (0.9%). Compared with other patients, low risk patients had a higher likelihood of freedom from obstructive coronary disease on index catheterization (85.1% vs. 44.2%, OR 4.84, 95% CI 4.06-5.77). Low risk patients had significantly higher survival (98.2% vs. 94.4%, OR 3.18, 95% CI 1.99-5.08), MI-free survival (97.2% vs. 91.9%, OR 3.03, 95% CI 2.07-4.45), and MI/revascularization-free survival (86.2 vs. 59.9%, OR 4.19, 95% CI 3.48-5.05) at 2 years than non-low risk patients. Operating characteristics for predicting the outcomes of interest varied modestly depending on the low-risk cut-point used but the positive predictive value for 2 year freedom from death was >98% regardless.
Conclusion
The PROMISE minimal-risk tool identifies 17% of stable chest pain patients referred to cardiac catheterization as low risk. These patients have a low prevalence of obstructive CAD and better survival than non-low risk patients. While this suggests that these patients are unlikely to benefit from catheterization, further research is needed to confirm a favorable downstream prognosis with medical management alone.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Aug 2021; 239:100-109
Nanna MG, Wang TY, Chiswell K, Sun JL, ... Fordyce CB, Douglas PS
Am Heart J: 30 Aug 2021; 239:100-109 | PMID: 34077743
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Impact:
Abstract

Validity of different dose reduction criteria for apixaban.

Hawkins NM, Er L, Sandhu RK, Kaul P, ... Levin A, Andrade JG
Reduced-dose apixaban is recommended in patients fulfilling 2 of 3 criteria: age ≥80 years, body weight ≤60 kg, and serum creatinine ≥1.5 mg/dL. However, patient weight is often not available in electronic health data. We examined the validity of alternative definitions based on age and renal function alone using an observational dataset of patients with atrial fibrillation and chronic kidney disease which included weight measurements.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Jul 2021; 238:12-15
Hawkins NM, Er L, Sandhu RK, Kaul P, ... Levin A, Andrade JG
Am Heart J: 30 Jul 2021; 238:12-15 | PMID: 33762178
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Impact:
Abstract

Clinical features and outcomes in patients with cardiogenic shock complicating acute myocardial infarction: early vs recent experience with impella.

Singh H, Mehta RH, O\'Neill W, Kapur NK, ... Rosman H, Kaki A
Objectives
To compare clinical features and outcomes in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) treated in the early experience with Impella percutaneous ventricular assist device and patients treated recently.
Background
Since pre-market approval (PMA) of Impella device as treatment for AMICS, use of the device has grown considerably.
Methods
We retrospectively analyzed 649 AMICS patients treated with perioperative Impella, with 291 patients treated from 2008 to 2014 comprising the early experience cohort and 358 patients treated from 2017 to 2019 comprising the recent experience cohort. The primary end point was risk adjusted in-hospital mortality.
Results
Mean age and gender distribution of patients was similar in the two cohorts. The recent cohort had more invasive hemodynamic monitoring (64% vs 46%; P < .001) and less use of an intra-aortic balloon pump prior to Impella (15% vs 41%; P < .001). Recently treated patients were significantly more likely to receive Impella support prior to PCI (58% vs 44%; P = .005). In-hospital mortality was lower in the recent cohort (48% vs 56%; P = .043). This difference was however no longer significant after risk adjustment (adjusted OR 0.89, 95% CI 0.59-1.34, P = .59). Rates of acute kidney injury, major bleeding, and vascular complications requiring surgery were also significantly lower in the recent cohort.
Conclusions
Use of Impella for AMICS during recent years is associated with lower unadjusted in-hospital mortality, which may reflect better patient selection, earlier device implantation, and improved management algorithms. In-depth understanding of these factors may inform the development of future treatment protocols.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Jul 2021; 238:66-74
Singh H, Mehta RH, O'Neill W, Kapur NK, ... Rosman H, Kaki A
Am Heart J: 30 Jul 2021; 238:66-74 | PMID: 33848505
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Impact:
Abstract

Neighborhood education status drives racial disparities in clinical outcomes in PPCM.

Getz KD, Lewey J, Tam V, Irizarry OC, ... Aplenc R, Arany Z
Background
Peripartum cardiomyopathy (PPCM) disproportionately affects women of African ancestry. Additionally, clinical outcomes are worse in this subpopulation compared to White women with PPCM.  The extent to which socioeconomic parameters contribute to these racial disparities is not known.
Methods
We aimed to quantify the association between area-based proxies of socioeconomic status (SES) and clinical outcomes in PPCM, and to determine the potential contribution of these factors to racial disparities in outcomes. A retrospective cohort study was performed at the University of Pennsylvania Health System, a tertiary referral center serving a population with a high proportion of Black individuals. The cohort included 220 women with PPCM, 55% of whom were Black or African American. Available data included clinical and demographic characteristics as well as residential address georeferenced to US Census-derived block group measures of SES. Rates of sustained cardiac dysfunction (defined as persistent LVEF <50%, LVAD placement, transplant, or death) were compared by race and block group-level measures of SES, and a composite neighborhood concentrated disadvantage index (NDI). The contributions of area-based socioeconomic parameters to the association between race and sustained cardiac dysfunction were quantified.
Results
Black race and higher NDI were both independently associated with sustained cardiac dysfunction (relative risk [RR] 1.63, confidence interval [CI] 1.13-2.36; and RR 1.29, CI 1.08-1.53, respectively). Following multivariable adjustment, effect size for NDI remained statistically significant, but effect size for Black race did not. The impact of low neighborhood education on racial disparities in outcomes was stronger than that of low neighborhood income (explaining 45% and 0% of the association with black race, respectively). After multivariate adjustment, only low area-based education persisted as significantly correlating with sustained cardiac dysfunction (RR 1.49; CI 1.02-2.17).
Conclusions
Both Black race and NDI independently associate with adverse outcomes in women with PPCM in a single center study. Of the specific components of NDI, neighborhood low education was most strongly associated with clinical outcome and partially explained differences in race. These results suggest interventions targeting social determinants of health in disadvantaged communities may help to mitigate outcome disparities.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Jul 2021; 238:27-32
Getz KD, Lewey J, Tam V, Irizarry OC, ... Aplenc R, Arany Z
Am Heart J: 30 Jul 2021; 238:27-32 | PMID: 33857409
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Impact:
Abstract

Rationale and design of a large population study to validate software for the assessment of atrial fibrillation from data acquired by a consumer tracker or smartwatch: The Fitbit heart study.

Lubitz SA, Faranesh AZ, Atlas SJ, McManus DD, ... Pantelopoulos A, Foulkes AS
Background
Early detection of atrial fibrillation or flutter (AF) may enable prevention of downstream morbidity. Consumer wrist-worn wearable technology is capable of detecting AF by identifying irregular pulse waveforms using photoplethysmography (PPG). The validity of PPG-based software algorithms for AF detection requires prospective assessment.
Methods
The Fitbit Heart Study (NCT04380415) is a single-arm remote clinical trial examining the validity of a novel PPG-based software algorithm for detecting AF. The proprietary Fitbit algorithm examines pulse waveform intervals during analyzable periods in which participants are sufficiently stationary. Fitbit consumers with compatible wrist-worn trackers or smartwatches were invited to participate. Enrollment began May 6, 2020 and as of October 1, 2020, 455,699 participants enrolled. Participants in whom an irregular heart rhythm was detected were invited to attend a telehealth visit and eligible participants were then mailed a one-week single lead electrocardiographic (ECG) patch monitor. The primary study objective is to assess the positive predictive value of an irregular heart rhythm detection for AF during the ECG patch monitor period. Additional objectives will examine the validity of irregular pulse tachograms during subsequent heart rhythm detections, self-reported AF diagnoses and treatments, and relations between irregular heart rhythm detections and AF episode duration and time spent in AF.
Conclusions
The Fitbit Heart Study is a large-scale remote clinical trial comprising a unique software algorithm for detection of AF. The study results will provide critical insights into the use of consumer wearable technology for AF detection, and for characterizing the nature of AF episodes detected using consumer-based PPG technology.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Jul 2021; 238:16-26
Lubitz SA, Faranesh AZ, Atlas SJ, McManus DD, ... Pantelopoulos A, Foulkes AS
Am Heart J: 30 Jul 2021; 238:16-26 | PMID: 33865810
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Impact:
Abstract

Electronic health record risk score provides earlier prognostication of clinical outcomes in patients admitted to the cardiac intensive care unit.

Kunitomo Y, Thomas A, Chouairi F, Canavan ME, ... Brennan J, Miller PE
In this observational study, we compared the prognostic ability of an electronic health record (EHR)-derived risk score, the Rothman Index (RI), automatically derived on admission, to the first 24-hour Sequential Organ Failure Assessment (SOFA) score for outcome prediction in the modern cardiac intensive care unit (CICU). We found that while the 24-hour SOFA score provided modestly superior discrimination for both in-hospital and CICU mortality, the RI upon CICU admission had better calibration for both outcomes. Given the ubiquitous nature of EHR utilization in the United States, the RI may become an important tool to rapidly risk stratify CICU patients within the ICU and improve resource allocation.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Jul 2021; 238:85-88
Kunitomo Y, Thomas A, Chouairi F, Canavan ME, ... Brennan J, Miller PE
Am Heart J: 30 Jul 2021; 238:85-88 | PMID: 33891906
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Impact:
Abstract

Effects of the PCSK9 antibody alirocumab on coronary atherosclerosis in patients with acute myocardial infarction: a serial, multivessel, intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography imaging study-Rationale and design of the PACMAN-AMI trial.

Zanchin C, Koskinas KC, Ueki Y, Losdat S, ... Windecker S, Räber L
Background
The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown.
Aims
To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI4 mm) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI.
Methods
In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI4 mm, and OCT-derived minimal FCT, will be assessed 52 weeks post randomization.
Summary
The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI.
Clinical trial registration
NCT03067844.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 Jul 2021; 238:33-44
Zanchin C, Koskinas KC, Ueki Y, Losdat S, ... Windecker S, Räber L
Am Heart J: 30 Jul 2021; 238:33-44 | PMID: 33951415
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Impact:
Abstract

Comparative effectiveness of team-based care with a clinical decision support system versus team-based care alone on cardiovascular risk reduction among patients with diabetes: Rationale and design of the D4C trial.

Shi X, He J, Lin M, Liu C, ... Yao G, Li X
Background
Diabetes has become a major public health challenge worldwide, especially in low- and middle-income countries (LMICs). Uncontrolled hyperglycemia, hypertension, and dyslipidemia major risk factors for all-cause mortality and cardiovascular disease (CVD) are common in patients with diabetes in China. We propose to compare the effectiveness of team-based care plus a clinical decision support system (CDSS) with team-based care alone on glycemic, blood pressure (BP), and lipid control, and clinical CVD reduction among patients with type-2 diabetes and at high risk for CVD.
Methods
The Diabetes Complication Control in Community Clinics (D4C) study is a cluster-randomized trial conducted among 38 community health centers in Xiamen City, China. Nineteen clinics have been randomly assigned to team-based care plus CDSS and 19 to team-based care alone. Team-based care includes primary care providers, health coaches, and diabetes specialists working collaboratively with patients to achieve shared treatment goals for CVD risk factor reduction. The CDSS integrates guideline-based treatment algorithms for glycemic, BP, and lipid control, along with a patient\'s medical history and insurance policy, to recommend treatment and follow-up plans. In phase 1, the co-primary outcomes are mean reduction in glycated hemoglobin (HbA1c), systolic BP (SBP), and low-density lipoprotein (LDL)-cholesterol over 18 months, and the proportion of patients with controlled HbA1c, SBP, and LDL-cholesterol at 18 months\' between the 2 comparison groups. In phase 2, the primary outcome is the difference in major CVD incidence (non-fatal stroke, non-fatal myocardial infarction, hospitalized heart failure, and CVD mortality) between the 2 comparison groups. Mean reduction in HbA1c, SBP, and LDL-cholesterol levels will be simultaneously modeled for a single overall treatment effect.
Conclusion
The D4C trial will generate evidence on whether a CDSS will further reduce the CVD burden among patients with diabetes beyond team-based care at community clinics. If proven effective, this implementation strategy could be scaled up within primary care settings in China and other LMICs to reduce CVD incidence and mortality among patients with diabetes.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Jul 2021; 238:45-58
Shi X, He J, Lin M, Liu C, ... Yao G, Li X
Am Heart J: 30 Jul 2021; 238:45-58 | PMID: 33957103
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Impact:
Abstract

Long-term prognostic outcomes and implication of oral anticoagulants in patients with new-onset atrial fibrillation following st-segment elevation myocardial infarction.

Madsen JM, Jacobsen MR, Sabbah M, Topal DG, ... Engstrøm T, Lønborg JT
Background
New-onset atrial fibrillation (NEW-AF) following ST-segment elevation myocardial infarction (STEMI) is a common complication, but the true prognostic impact of NEW-AF is unknown. Additionally, the optimal treatment of NEW-AF among patients with STEMI is warranted.
Methods
A large cohort of consecutive patients with STEMI treated with percutaneous coronary intervention were identified using the Eastern Danish Heart Registry from 1999-2016. Medication and end points were retrieved from Danish nationwide registries. NEW-AF was defined as a diagnosis of AF within 30 days following STEMI. Patients without a history of AF and alive after 30 days after discharge were included. Incidence rates were calculated and multivariate analyses performed to determine the association between NEW-AF and long-term mortality, incidence of ischemic stroke, re-MI, and bleeding leading to hospitalization, and the comparative effectiveness of OAC therapy on these outcomes.
Results
Of 7944 patients with STEMI, 296 (3.7%) developed NEW-AF. NEW-AF was associated with increased long-term mortality (adjusted HR 1.48, 95% CI 1.20-1.82, P<.001) and risk of bleeding leading to hospitalization (adjusted HR 1.36, 95% CI 1.00-1.85, P=.050), and non-significant increased risk of ischemic stroke (adjusted HR 1.45, 95% CI 0.96-2.19, P=.08) and re-MI (adjusted HR 1.14, 95% CI 0.86-1.52, P=.35) with a median follow-up of 5.8 years. In NEW-AF patients, 38% received OAC therapy, which was associated with reduced long-term mortality (adjusted HR 0.69, 95% CI 0.47-1.00, P=.049).
Conclusions
NEW-AF following STEMI is associated with increased long-term mortality. Treatment with OAC therapy in NEW-AF patients is associated with reduced long-term mortality.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Jul 2021; 238:89-99
Madsen JM, Jacobsen MR, Sabbah M, Topal DG, ... Engstrøm T, Lønborg JT
Am Heart J: 30 Jul 2021; 238:89-99 | PMID: 33957102
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Impact:
Abstract

Financial burden, distress, and toxicity in cardiovascular disease.

Slavin SD, Khera R, Zafar SY, Nasir K, Warraich HJ
Cardiovascular disease (CVD) is a major source of financial burden and distress, which has 3 main domains: (1) psychological distress; (2) cost-related care non-adherence or medical care deferral, and (3) tradeoffs with basic non-medical needs. We propose 4 ways to reduce financial distress in CVD: (1) policymakers can expand insurance coverage and curtail underinsurance; (2) health systems can limit expenditure on low-benefit, high-cost treatments while developing services for high-risk individuals; (3) physicians can engage in shared-decision-making for high-cost interventions, and (4) community-based initiatives can support patients with system navigation and financial coping. Avenues for research include (1) analysis of how healthcare policies affect financial burden; (2) comparative effectiveness studies examining high and low-cost strategies for CVD management; and (3) studying interventions to reduce financial burden, financial coaching, and community health worker integration.

Published by Elsevier Inc.

Am Heart J: 30 Jul 2021; 238:75-84
Slavin SD, Khera R, Zafar SY, Nasir K, Warraich HJ
Am Heart J: 30 Jul 2021; 238:75-84 | PMID: 33961830
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Impact:
Abstract

Cangrelor vs. glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention.

Yerasi C, Case BC, Chezar-Azerrad C, Forrestal BJ, ... Garcia-Garcia HM, Waksman R
Background
To date, there are no real-world studies comparing cangrelor to glycoprotein IIb/IIIa inhibitors (GPI) during percutaneous coronary intervention (PCI). Thus, we performed this study to evaluate the safety and effectiveness of cangrelor compared to GPI during PCI.
Methods
We identified patients who underwent PCI at our institution who received either cangrelor or GPI during PCI. Patients already on GPI or cangrelor prior to PCI or who received both cangrelor and GPI were excluded. Baseline demographics and clinical outcomes were extracted. Major bleeding is defined as a composite of major hematoma >4 cm, hematocrit drop >15, and gastrointestinal bleeding.
Results
A total of 2072 patients received adjunctive antiplatelet therapy during PCI (cangrelor [n=478]; GPI [n=1594]). Patients\' mean age was 61±12 years. Most (66%) presented with acute coronary syndrome. Patients who received cangrelor were older and had a higher percentage of acute coronary syndrome and lower baseline hematocrit in comparison with patients who received GPI. Procedural success was achieved in 94% of patients, with no difference between groups. Major bleeding events (1.7% vs. 5.1%, P=.001), any vascular complication rates, and hospital length of stay were significantly lower in the cangrelor group. In-hospital ischemic events did not differ between groups. On regression analysis, patients on cangrelor were noted to have significantly lower major bleeding events (OR 0.23; 95% CI, 0.09-0.59).
Conclusions
Balancing ischemic and bleeding risks with adjunctive antiplatelet drugs is of prime importance during PCI. Our real-world analysis shows that cangrelor is safe and effective when compared to GPI during PCI.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 Jul 2021; 238:59-65
Yerasi C, Case BC, Chezar-Azerrad C, Forrestal BJ, ... Garcia-Garcia HM, Waksman R
Am Heart J: 30 Jul 2021; 238:59-65 | PMID: 33961829
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Impact:
Abstract

The FULL REVASC (Ffr-gUidance for compLete non-cuLprit REVASCularization) Registry-based Randomized Clinical Trial.

Böhm F, Mogensen B, Östlund O, Engstrøm T, ... Rück A, James SK
Background
Complete revascularization in ST elevation myocardial infarction (STEMI) patients with multivessel disease has resulted in reduction in composite clinical endpoints in medium sized trials. Only one trial showed an effect on hard clinical endpoints, but the revascularization procedure was guided by angiographic evaluation of stenosis severity. Consequently, it is not clear how Fractional Flow Reserve (FFR)-guided percutaneous coronary intervention (PCI) affects hard clinical endpoints in STEMI.
Methods and results
The Ffr-gUidance for compLete non-cuLprit REVASCularization (FULL REVASC) - is a pragmatic, multicenter, international, registry-based randomized clinical trial designed to evaluate whether a strategy of FFR-guided complete revascularization of non-culprit lesions, reduces the combined primary endpoint of total mortality, non-fatal MI and unplanned revascularization. 1,545 patients were randomized to receive FFR-guided PCI during the index hospitalization or initial conservative management of non-culprit lesions. We found that in angiographically severe non-culprit lesions of 90-99% severity, 1 in 5 of these lesions were re-classified as non-flow limiting by FFR. Considering lesions of intermediate severity (70-89%), half were re-classified as non-flow limiting by FFR. The study is event driven for an estimated follow-up of at least 2.75 years to detect a 9.9%/year>7.425%/year difference (HR=0.74 at 80% power (α = .05)) for the combined primary endpoint.
Conclusion
This large randomized clinical trial is designed and powered to evaluate the effect of complete revascularization with FFR-guided PCI during index hospitalization on total mortality, non-fatal MI and unplanned revascularization following primary PCI in STEMI patients with multivessel disease. Enrollment completed in September 2019 and follow-up is ongoing.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 22 Jul 2021; epub ahead of print
Böhm F, Mogensen B, Östlund O, Engstrøm T, ... Rück A, James SK
Am Heart J: 22 Jul 2021; epub ahead of print | PMID: 34310907
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Impact:
Abstract

Implementation of a Practice Plan for the Outpatient Cardiac Evaluation of Children after Acute SARS-CoV-2 Infection and a Report of Outcomes.

Dailey-Schwartz AL, Dyal JA, Mahle WT, Oster ME
SARS-CoV-2 infection has been associated with cardiovascular disease in children, but which children need cardiac evaluation is unclear. We describe our experience evaluating 206 children for cardiac disease following SARS-CoV-2 infection (one of whom had ventricular ectopy) and propose a new guideline for management of these children. Routine cardiac screening after SARS-CoV-2 infection in children without any cardiac signs or symptoms does not appear to be high yield.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 20 Jul 2021; epub ahead of print
Dailey-Schwartz AL, Dyal JA, Mahle WT, Oster ME
Am Heart J: 20 Jul 2021; epub ahead of print | PMID: 34302751
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Impact:
Abstract

Development and outcomes of hyperkalemia in hospitalized patients: potential implications for care.

Wetmore JB, Yan H, Peng Y, Gilbertson DT, Herzog CA
Introduction
While severe hyperkalemia is commonly encountered, its manifestation in hospitalized patients and related outcomes are unclear. We aimed to examine development of hyperkalemia in hospitalized patients and associated outcomes.
Methods
Data from a county hospital electronic health record were used to assess all inpatient admissions, 2012-2016, for non-dialysis-dependent patients with ≥1 K value for development of hyperkalemia. Unadjusted odds ratios (ORs) were calculated for associations of the maximum K value with in-hospital mortality and adjusted ORs were calculated for death associated with hyperkalemia.
Results
In 47,018 individual patient hospitalizations, 1.3% had a maximum K ≥6.0 mEq/L and 4.2% <3.5 mEq/L. Fifth and 95th percentiles for maximum K values were 3.5 and 5.3 mEq/L. For high-K patients with a prior K value, the mean (SD) of the immediate pre-maximum K value was 5.0±1.0 mEq/L, and the mean difference in K values (immediate pre-maximum to maximum) was 1.5±1.1 mEq/L; mean duration between these two K tests was 10.7±14.9 hours. Compared with maximum K values 3.5-4.0 mEq/L, ORs for death were 37.1 (95% confidence intervals, 25.8-53.3) for K 6.0-<6.5, 88.6 (56.8-138.2) for K ≥7.0, and 18.9 (4.3-82.2) for K <3.0 mEq/L. In adjusted models, the OR for death for K ≥6.0 mEq/L was 4.9 (3.7-6.4).
Discussion/conclusion
Peak K values ≥6.0 mEq/L were associated with mortality. Values tended to increase rapidly, limiting opportunities for detection and treatment. Systems-based approaches to detect life-threatening hyperkalemia should be studied.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 18 Jul 2021; epub ahead of print
Wetmore JB, Yan H, Peng Y, Gilbertson DT, Herzog CA
Am Heart J: 18 Jul 2021; epub ahead of print | PMID: 34293294
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Impact:
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 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 (LA) remodeling and pulmonary hypertension. We assessed LV systolic stiffness using end-systolic elastance (Ees), and diastolic stiffness using LV stiffness constant (β) and chamber capacitance (LV-end-diastolic volume at an end-diastolic pressure of 20mmHg, LVEDVI20)
Results:
: There were 112 patients in each group. Although both groups had similar systolic BP, the COA group had a higher Ees (2.37±0.74 vs 2.11±0.54 mmHg/ml, p=0.008), higher β (6.91±0.81 vs 5.93±0.79, p=0.006) and lower LVEDVI20 (58±9 vs 67±11 ml/m2, p<0.001). Additionally, the COA group had more advanced LA 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: 17 Jul 2021; epub ahead of print
Egbe AC, Miranda WR, Connolly HM, Borlaug BA
Am Heart J: 17 Jul 2021; epub ahead of print | PMID: 34289342
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Abstract

Move more - be happier? Physical Activity and Health-Related Quality of Life in Children with Congenital Heart Disease.

Brudy L, Meyer M, Oberhoffer R, Ewert P, Müller J
Objective
This cross-sectional study aimed to determine whether there is an association between objectively assessed physical activity (PA) and health-related quality of life (HRQoL) in children with CHD.
Patients and methods
From September 2017 to January 2021, 343 children with CHD (12.1 ± 3.3 years, 135 girls) provided valid PA data after a 7-day objective PA assessment. PA was evaluated as average daily steps and moderate-to-vigorous physical activity (MVPA) minutes assessed via wearable bracelet Garmin vivofit® Jr. These children also completed the KINDL® - a 24 Likert-scaled item questionnaire assessing HRQoL in the six dimensions physical well-being, emotional well-being, self-esteem, family, friends and everyday functioning.
Results
Daily Steps (r=.166, p=.003) and daily MVPA minutes (r=.134, p=.017,) were both correlated to total KINDL® score. Furthermore, both steps and MVPA were associated with the subscales physical well-being (steps: r=.165 p=.003; MVPA: r=.129, p=.022), friends (steps: r=.210, p<.001, MVPA: r=.179, p=.001), and steps also to everyday functioning (r=.142, p=.012). Logistic regression showed each MVPA minute increase conferred to a 1% increase in reporting better HRQoL (OR: 1.009 [95% CI: 1.002 - 1.017], p=.019).
Conclusions
PA was positively associated with HRQoL in children with CHD. Patients who move more are more likely to report better HRQoL. While the magnitude of this association needs to be further understood, continuous encouragement towards more PA seems to be crucial in a holistic approach to medical aftercare in children with CHD.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 17 Jul 2021; epub ahead of print
Brudy L, Meyer M, Oberhoffer R, Ewert P, Müller J
Am Heart J: 17 Jul 2021; epub ahead of print | PMID: 34289343
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Impact:
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. Published by Elsevier Inc.

Am Heart J: 16 Jul 2021; epub ahead of print
Moghaddam N, Malhi N, Toma M
Am Heart J: 16 Jul 2021; epub ahead of print | PMID: 34283990
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Impact:
Abstract

Admission Rates During a Second COVID-19 Lockdown.

Christensen DM, Butt JH, Fosbøl E, Køber L, ... Gislason G, Phelps M
Societal lockdowns during the first wave of the COVID-19 pandemic were associated with decreased admission rates for acute cardiovascular conditions worldwide. In this nationwide Danish study of the first five weeks of a second pandemic lockdown, incidence of new-onset heart failure and atrial fibrillation remained stable, but there was a significant drop in new-onset ischemic heart disease and ischemic stroke during the fourth week of lockdown, which normalized promptly. The observed drops were lower compared to the first Danish lockdown in March 2020; thus, our data suggest that declines in acute CVD admission rates during future lockdowns are avoidable.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 14 Jul 2021; epub ahead of print
Christensen DM, Butt JH, Fosbøl E, Køber L, ... Gislason G, Phelps M
Am Heart J: 14 Jul 2021; epub ahead of print | PMID: 34274314
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Impact:
Abstract

Association of STEMI Regionalization of Care with De Facto NSTEMI Regionalization.

Montoy JCC, Shen YC, Krumholz HM, Hsia RY
The regionalization of care for ST elevation myocardial infarction (STEMI) may unintentionally concentrate patients with non-ST elevation myocardial infarction (NSTEMI) into percutaneous coronary intervention (PCI) capable hospitals. This could lead to benefits such as increased access to PCI-capable hospitals, but could cause harms such as crowding in some hospitals with decreased patient volume and revenue in others. We set out to assess whether STEMI regionalization programs concentrated patients with NSTEMI at STEMI-receiving hospitals.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 14 Jul 2021; epub ahead of print
Montoy JCC, Shen YC, Krumholz HM, Hsia RY
Am Heart J: 14 Jul 2021; epub ahead of print | PMID: 34274313
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Impact:
Abstract

Rationale and design of a digital trial using smartphones to detect subclinical atrial fibrillation in a population at risk: The eHealth-based Bavarian Alternative Detection of Atrial Fibrillation (eBRAVE-AF) trial.

Freyer L, von Stülpnagel L, Spielbichler P, Sappler N, ... Rizas KD, Bauer A
Current guidelines recommend opportunistic screening for subclinical atrial fibrillation (AF) taking advantage of e-health-based technologies. However, the efficacy of a fully scalable e-health-based strategy for AF detection in a head-to-head comparison with routine symptom-based screening is unknown. eBRAVE-AF is an investigator-initiated, digital, prospective, randomized, siteless, open-label, cross-over study to evaluate an e-health-based strategy for detection of AF in a real-world setting. 67,488 policyholders of a large German health insurance company (Versicherungskammer Bayern, Germany) selected by age ≥ 50 years and a CHA2DS2-VASc score ≥ 1 (females ≥2) are invited to participate. Subjects with known AF or on treatment with oral anticoagulation are excluded. After obtaining electronic informed consent, at least 4,400 participants will be randomly assigned to an e-health-based screening strategy or routine symptom-based screening. The e-health-based strategy consists of repetitive one-minute photoplethysmographic (PPG) pulse wave assessments using a certified smartphone app (Preventicus Heartbeats, Preventicus, Jena, Germany), followed by a confirmatory 14-day ECG patch (CardioMem CM 100 XT, Getemed, Teltow, Germany) in case of abnormal findings. After 6 months, participants are crossed over to the other study arm. Primary endpoint is the incidence of newly diagnosed AF leading to oral anticoagulation indicated by an independent physician. Clinical follow-up will be at least 12 months. In both groups, follow-up is performed by 4-week app-based questionnaires, personal contact in case of abnormal findings, and matching with claim-based insurance data and medical reports. At time of writing enrollment is completed. First results are expected to be available in mid-2021.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 08 Jul 2021; epub ahead of print
Freyer L, von Stülpnagel L, Spielbichler P, Sappler N, ... Rizas KD, Bauer A
Am Heart J: 08 Jul 2021; epub ahead of print | PMID: 34252387
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Impact:
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: 01 Jul 2021; epub ahead of print
Povsic TJ, Henry TD, Ohman EM, Pepine CJ, ... Answini GA, Mokadam NA
Am Heart J: 01 Jul 2021; epub ahead of print | PMID: 34224684
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Impact:
Abstract

Natriuretic peptide plasma concentrations and risk of cardiovascular versus non-cardiovascular events in heart failure with reduced ejection fraction: Insights from the PARADIGM-HF and ATMOSPHERE trials.

Khan MS, Kristensen SL, Vaduganathan M, Kober L, ... McMurray JJ, Butler J
Background
N-terminal pro-B-type natriuretic peptide (NT-proBNP) plasma concentrations are independent prognostic markers in patients with heart failure and reduced ejection fraction (HFrEF). Whether a differential risk association between NT-proBNP plasma concentrations and risk of cardiovascular (CV) vs non-CV adverse events exists is not well known.
Objective
To assess if there is a differential proportional risk of CV vs non-CV adverse events by NT-proBNP plasma concentrations.
Methods
In this post hoc combined analysis of PARADIGM-HF and ATMOSPHERE trials, proportion of CV vs non-CV mortality and hospitalizations were assessed by NT-proBNP levels (<400, 400-999, 1000-1999, 2000-2999, and >3000 pg/mL) at baseline using Cox regression adjusting for traditional risk factors.
Results
A total of 14,737 patients with mean age of 62 ± 8 years (24% history of atrial fibrillation [AF]) were studied. For CV deaths, the event rates per 1000 patient-years steeply increased from 33.8 in the ≤400 pg/mL group to 142.3 in the ≥3000 pg/mL group, while the non-CV death event rates modestly increased from 9.0 to 22.7, respectively. Proportion of non-CV deaths decreased across the 5 NT-proBNP groups (21.1%, 18.4%, 17.9%, 17.4%, and 13.7% respectively). Similar trend was observed for non-CV hospitalizations (46.4%, 42.6%, 42.9%, 42.0%, and 36.9% respectively). These results remained similar when stratified according to the presence of AF at baseline and prior HF hospitalization within last 12 months.
Conclusions
The absolute CV event rates per patient years of follow-up were greater and had higher stepwise increases than non-CV event rates across a broad range of NT-proBNP plasma concentrations indicating a differential risk of CV events at varying baseline NT-proBNP values. These results have implications for future design of clinical trials.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Jun 2021; 237:45-53
Khan MS, Kristensen SL, Vaduganathan M, Kober L, ... McMurray JJ, Butler J
Am Heart J: 29 Jun 2021; 237:45-53 | PMID: 33621540
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Impact:
Abstract

Efficacy of a centralized, blended electronic, and human intervention to improve direct oral anticoagulant adherence: Smartphones to improve rivaroxaban ADHEREnce in atrial fibrillation (SmartADHERE) a randomized clinical trial.

Turakhia M, Sundaram V, Smith SN, Ding V, ... Mahaffey KW, smartADHERE Investigators
Background
Improving adherence to direct oral anticoagulants (DOAC) is challenging, and simple text messaging reminders have not been effective.
Methods
SmartADHERE was a randomized trial that tested a personalized digital and human direct oral anticoagulant adherence intervention compared to usual care. Eligibility required age ≥ 18, newly-prescribed (≤90 days) rivaroxaban for atrial fibrillation (AF), 1 of 4 at-risk criteria for nonadherence, and a smartphone. The intervention consisted of combination of a medication management smartphone app, daily app-based reminders, adaptive text messaging, and phone-based counseling for severe nonadherence. The primary outcome was the proportion of days covered by rivaroxaban (PDC) at 6 months. There were 25 U.S. sites, all cardiology and electrophysiology outpatient practices, activated for a target sample size of 378, but the study was terminated by the sponsor prior to reaching target enrollment.
Results
There were 139 participants (age 65±9.6 years, 30% female, median CHA2DS2-VASc score 3 with IQR 2 to 4, mean total medication burden 7.7±4.4). DOAC adherence was high in both arms with no difference in the primary outcome (PDC 0.86±0.25 intervention vs 0.88±0.25 control, p=0.62) or in secondary outcomes including PDC ≥ 0.80 and medication persistence. Per protocol analyses had similar results. Because of the high overall PDC, the likelihood to answer the primary hypothesis was only 51% even if target enrollment were achieved. There were no study-related adverse events.
Conclusions
The use of a centralized digital and human adherence intervention was feasible across multiple sites. Overall adherence was much higher than expected despite prescreening for at-risk individuals. SmartADHERE illustrates the challenges of trials of behavioral and technology interventions, where enrollment itself may lead to selection bias or treatment effects. Pragmatic study designs, such as cluster randomization or stepped-wedge implementation, should be considered to improve enrollment and generalizability.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 29 Jun 2021; 237:68-78
Turakhia M, Sundaram V, Smith SN, Ding V, ... Mahaffey KW, smartADHERE Investigators
Am Heart J: 29 Jun 2021; 237:68-78 | PMID: 33676886
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Impact:
Abstract

Effect of a smartphone-based intervention on secondary prevention medication prescriptions after coronary artery bypass graft surgery: The MISSION-1 randomized controlled trial.

Qu J, Du J, Rao C, Chen S, ... Zheng Z, MISSION-1 Collaborative Group
Background
Studies found that patients who underwent coronary artery bypass grafting (CABG) often fail to receive optimal evidence-based secondary prevention medications. We evaluated the effectiveness of a smartphone-based quality improvement effort on improving the prescription of medical therapies.
Methods
In this cluster-randomized controlled trial, 60 hospitals were randomized to a control arm (n = 30) or to an intervention arm using smartphone-based multifaceted quality improvement interventions (n = 30). The primary outcome was the prescription of statin. The secondary outcomes were prescription of beta-blocker, angiotensin-converting enzyme inhibitor, or angiotensin receptor blocker (ACE inhibitor or ARB), and optimal medical therapy for eligible patients.
Results
Between June 1, 2015 and September 15, 2016, a total of 10,006 CABG patients were enrolled (5,653 in 26 intervention and 4,353 in 29 control hospitals, 5 hospitals withdrew). Statin prescribing rate was 87.8% in the intervention arm and 84.4% in the control arm. We saw no evidence of an effect of intervention on statin prescribing in the intention-to-treat analysis (odds ratio [OR], 1.31; 95% confidence interval (CI), 0.68-2.54; P = .43) or in key patient subsets. The prescription rates of ACE inhibitor or ARB and optimal medical therapy were comparable between study groups, while beta-blocker was more often prescribed in the intervention arm. Post hoc analysis demonstrated a greater increase in statin prescribing rate over time in the intervention arm.
Conclusions
A smartphone-based quality improvement intervention compared with usual care did not increase statin prescribing for patients who received CABG. New studies focusing on the best practice of this technique may be warranted.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Jun 2021; 237:79-89
Qu J, Du J, Rao C, Chen S, ... Zheng Z, MISSION-1 Collaborative Group
Am Heart J: 29 Jun 2021; 237:79-89 | PMID: 33689732
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Impact:
Abstract

Comparison of Outcomes with Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS trial): Rationale and design for a multi-center randomized controlled trial.

Aminorroaya A, Tavolinejad H, Sadeghian S, Jalali A, ... Ngarmukos T, Tajdini M
Background
The cornerstone of the treatment of vasovagal syncope (VVS) is lifestyle modifications; however, some patients incur life-disturbing attacks despite compliance with these treatments which underscores the importance of pharmacological interventions.
Methods
In this open-label multi-center randomized controlled trial, we are going to randomize 1375 patients with VVS who had ≥2 syncopal episodes in the last year into three parallel arms with a 2:2:1 ratio to receive midodrine, fludrocortisone, or no medication. All patients will be recommended to drink 2 to 3 liters of fluids per day, consume 10 grams of NaCl per day, and practice counter-pressure maneuvers. In medication arms, patients will start on 5 mg of midodrine TDS or 0.05 mg of fludrocortisone BD. After one week the dosage will be up-titrated to midodrine 30 mg/day and fludrocortisone 0.2 mg/day. Patient tolerance will be the principal guide to dosage adjustments. We will follow-up the patients on 3, 6, 9, and 12 months after randomization. The primary outcome is the time to first syncopal episode. Secondary outcomes include the recurrence rate of VVS, time interval between first and second episodes, changes in quality of life (QoL), and major and minor adverse drug reactions. QoL will be examined by the 36-Item Short Form Survey questionnaire at enrollment and 12 months after randomization.
Conclusion
The COMFORTS trial is the first study that aims to make a head-to-head comparison between midodrine and fludrocortisone, against a background of lifestyle modifications for preventing recurrences of VVS and improving QoL in patients with VVS.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Jun 2021; 237:5-12
Aminorroaya A, Tavolinejad H, Sadeghian S, Jalali A, ... Ngarmukos T, Tajdini M
Am Heart J: 29 Jun 2021; 237:5-12 | PMID: 33689731
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Impact:
Abstract

Randomized comparison of early supplemental oxygen versus ambient air in patients with confirmed myocardial infarction: Sex-related outcomes from DETO2X-AMI.

Alfredsson J, James SK, Erlinge D, Herlitz J, ... Hofmann R, DETO2X-SWEDEHEART Investigators
Background
The purpose of this study is to investigate the impact of oxygen therapy on cardiovascular outcomes in relation to sex in patients with confirmed myocardial infarction (MI).
Methods
The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction trial randomized 6,629 patients to oxygen at 6 L/min for 6-12 hours or ambient air. In the present subgroup analysis including 5,010 patients (1,388 women and 3,622 men) with confirmed MI, we report the effect of supplemental oxygen on the composite of all-cause death, rehospitalization with MI, or heart failure at long-term follow-up, stratified according to sex.
Results
Event rate for the composite endpoint was 18.1% in women allocated to oxygen, compared to 21.4% in women allocated to ambient air (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.65-1.05). In men, the incidence was 13.6% in patients allocated to oxygen compared to 13.3% in patients allocated to ambient air (HR 1.03, 95% CI 0.86-1.23). No significant interaction in relation to sex was found (P= .16). Irrespective of allocated treatment, the composite endpoint occurred more often in women compared to men (19.7 vs 13.4%, HR 1.51; 95% CI, 1.30-1.75). After adjustment for age alone, there was no difference between the sexes (HR 1.06, 95% CI 0.91-1.24), which remained consistent after multivariate adjustment.
Conclusion
Oxygen therapy in normoxemic MI patients did not significantly affect all-cause mortality or rehospitalization for MI or heart failure in women or men. The observed worse outcome in women was explained by differences in baseline characteristics, especially age.

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

Am Heart J: 29 Jun 2021; 237:13-24
Alfredsson J, James SK, Erlinge D, Herlitz J, ... Hofmann R, DETO2X-SWEDEHEART Investigators
Am Heart J: 29 Jun 2021; 237:13-24 | PMID: 33689730
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Impact:
Abstract

Transcatheter aortic valve replacement in low-risk patients: 2-year results from the LRT trial.

Waksman R, Torguson R, Medranda GA, Shea C, ... Satler LF, Rogers T
Background
Previous studies from the Low Risk TAVR (LRT) trial demonstrated that transcatheter aortic valve replacement (TAVR) is safe and feasible in low-risk patients, with excellent 30-day and 1-year outcomes. The objective of this study was to report clinical outcomes and the impact of 30-day hypoattenuated leaflet thickening (HALT) on structural valve deterioration (SVD) 2 years after TAVR.
Methods
The LRT trial was the first Food and Drug Administration-approved Investigational Device Exemption trial in the United States to evaluate the safety and feasibility of TAVR in low-risk patients with symptomatic severe tricuspid aortic stenosis (AS). Valve hemodynamics and SVD by echo were recorded 30 days, 1 year, and 2 years post-TAVR.
Results
The LRT trial enrolled 200 low-risk patients to receive TAVR. Their mean age was 73.6 years and 61.5% were men. At 2-year follow-up, the mortality rate was 4.2%; the cardiovascular death rate was 1.6%. The disabling stroke rate was 1.1%, permanent pacemaker implantation rate was 8.6%, and 4 patients (2.2%) presented with endocarditis (2 between years 1 and 2). Of the 14% of TAVR subjects who had evidence of HALT at 30 days, there was no impact on valve hemodynamics, endocarditis or stroke at 2 years.
Conclusions
TAVR for low-risk patients with symptomatic severe tricuspid AS is safe at 2 years. The presence of HALT at 30 days did not impact the early hemodynamic improvements nor the durability of the valve structure.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Jun 2021; 237:25-33
Waksman R, Torguson R, Medranda GA, Shea C, ... Satler LF, Rogers T
Am Heart J: 29 Jun 2021; 237:25-33 | PMID: 33713618
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Impact:
Abstract

To Adjust or Not to Adjust: The Role of Different Covariates in Cardiovascular Observational Studies.

Etminan M, Brophy JM, Collins G, Nazemipour M, Mansournia MA
Covariate adjustment is integral to the validity of observational studies assessing causal effects. It is common practice to adjust for as many variables as possible in observational studies in the hopes of reducing confounding by other variables. However, indiscriminate adjustment for variables using standard regression models may actually lead to biased estimates. In this paper, we differentiate between confounders, mediators, colliders, and effect modifiers. We will discuss that while confounders should be adjusted for in the analysis, one should be wary of adjusting for colliders. Mediators should not be adjusted for when examining the total effect of an exposure on an outcome. Automated statistical programs should not be used to decide which variables to include in causal models. Using a case scenario in cardiology, we will demonstrate how to identify confounders, colliders, mediators and effect modifiers and the implications of adjustment or non-adjustment for each of them.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Jun 2021; 237:62-67
Etminan M, Brophy JM, Collins G, Nazemipour M, Mansournia MA
Am Heart J: 29 Jun 2021; 237:62-67 | PMID: 33722586
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Impact:
Abstract

Effectiveness of the quadrivalent high-dose influenza vaccine for prevention of cardiovascular and respiratory events in people aged 65 years and above: Rationale and design of a real-world pragmatic randomized clinical trial.

Hollingsworth R, Palmu A, Pepin S, Dupuy M, ... Samson S, De Bruijn I
Background
Influenza has been an acknowledged cause of respiratory disease for decades. However, considerable related, and often unappreciated, disease burden stems from cardiovascular complications, exacerbations of underlying medical conditions and secondary respiratory complications, with the highest burden in the elderly. This novel study combines the gold standard method of a randomized controlled trial with real-world data collection through national registries, to assess the relative effectiveness of high-dose (QIV-HD) vs standard-dose quadrivalent influenza vaccine (QIV-SD) in preventing cardio-respiratory hospitalizations in a large cohort of adults aged ≥65 years.
Methods and results
This trial (NCT04137887) is a Phase III/IV, modified double-blinded, randomized, registry-based trial, conducted by the Finnish Institute for Health and Welfare (THL). Participants (n>120 000) are being enrolled over multiple influenza seasons and randomized (1:1) to receive QIV-HD or QIV-SD. Participant follow-up is based on data collection up to 11 months post-vaccination using Finnish national health registries. The primary objective is to demonstrate the relative superior effectiveness of QIV-HD over QIV-SD in preventing cardio-respiratory hospitalizations up to 6 months post-vaccination. Safety will be assessed using automated online tools throughout the study, with causality assessed using statistical and probabilistic methods; serious adverse reactions and adverse events of special interest will be investigated individually.
Conclusion
This large, real-world, randomized study will provide valuable insight into the contribution of influenza in causing severe cardio-respiratory events, and the role of vaccination with QIV-HD in reducing these outcomes compared to the current standard of care.
Funding
Sanofi Pasteur.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 29 Jun 2021; 237:54-61
Hollingsworth R, Palmu A, Pepin S, Dupuy M, ... Samson S, De Bruijn I
Am Heart J: 29 Jun 2021; 237:54-61 | PMID: 33722585
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Impact:
Abstract

Sex disparities in patients with symptomatic severe aortic stenosis.

Lowenstern A, Sheridan P, Wang TY, Boero I, ... Peterson ED, Brennan JM
Background
We evaluated whether there is equitable distribution across sexes of treatment and outcomes for aortic valve replacement (AVR), via surgical (SAVR) or transcatheter (TAVR) methods, in symptomatic severe aortic stenosis (ssAS) patients.
Methods
Using de-identified data, we identified 43,822 patients with ssAS (2008-2016). Multivariate competing risk models were used to determine the likelihood of any AVR, while accounting for the competing risk of death. Association between sex and 1-year mortality, stratified by AVR status, was evaluated using multivariate Cox regression models with AVR as a time-dependent variable.
Results
Among patients with ssAS, 20,986 (47.9%) were female. Females were older (median age 81 vs. 78, P<0.001), more likely to have body mass index <20 (8.5% vs. 3.5%), and home oxygen use (4.4% vs. 3.4%, P<0001 for all). Overall, 12,129 (27.7%) patients underwent AVR for ssAS. Females were less likely to undergo AVR compared with males (24.1% vs. 31.0%, adjusted hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.77-0.83), but when treated, were more likely to undergo TAVR (37.9% vs. 30.9%, adjusted HR 1.21, 95% CI 1.15-1.27). Untreated females and males had similarly high rates of mortality at 1 year (31.1% vs. 31.3%, adjusted HR 0.98, 95% CI 0.94-1.03). Among those undergoing AVR, females had significantly higher mortality (10.2% vs. 9.4%, adjusted HR 1.24, 95% CI 1.10-1.41), driven by increased SAVR-associated mortality (9.0% vs. 7.6%, adjusted HR 1.43, 95% CI 1.21-1.69).
Conclusions
Treatment rates for ssAS patients remain suboptimal with disparities in female treatment.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 29 Jun 2021; 237:116-126
Lowenstern A, Sheridan P, Wang TY, Boero I, ... Peterson ED, Brennan JM
Am Heart J: 29 Jun 2021; 237:116-126 | PMID: 33722584
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Impact:
Abstract

Potent P2Y12 inhibitors versus Clopidogrel in elderly patients with acute coronary syndrome: Systematic review and meta-analysis.

Fujisaki T, Kuno T, Ando T, Briasoulis A, Takagi H, Bangalore S
Background
Potent P2Y12 inhibitors reduce cardiovascular events but increase bleeding in patients presenting with acute coronary syndrome (ACS). Elderly patients are at increased risk of bleeding and whether the benefit-risk ratio of potent P2Y12 inhibitors remains favorable is not known.
Objectives
To investigate the efficacy and safety of potent P2Y12 inhibitors versus clopidogrel in elderly patients with ACS.
Methods
PUBMED and EMBASE were searched through July 2020 for randomized control trials (RCTs) or subgroup analyses of RCTs investigating potent P2Y12 inhibitors (prasugrel or ticagrelor) or clopidogrel in elderly (age ≥ 65 years) patients with ACS. The primary outcome was major adverse cardiovascular events (MACE).
Results
Our search identified 9 RCTs with a total of 10,792 elderly patients. When compared with clopidogrel, potent P2Y12 inhibitors had similar risk of MACE (hazard ratio (HR): 0.94; 95%; confidence interval (CI) [0.85-1.06], P = .31, I2 = 9%), all-cause mortality (HR: 0.89; 95% CI [0.74-1.07], P = .22, I2 = 29%), reduced the risk of cardiovascular death (HR: 0.82; 95% CI [0.68-0.98], P = .03, I2 = 16%) but increased the risk of major bleeding (HR: 1.27; 95% CI [1.04-1.56], P = .02, I2 = 0%). In a subgroup analysis, ticagrelor reduced all-cause mortality (HR: 0.73; 95% CI [0.55-0.98]) and cardiovascular death (HR: 0.70; 95% CI [0.54-0.90]) compared with clopidogrel.
Conclusions
Among elderly patients with ACS, potent P2Y12 inhibitors reduce cardiovascular death but increase bleeding with no difference in MACE or all-cause death when compared with clopidogrel. Further RCTs are needed to refine P2Y12 inhibitor selection for elderly patients with ACS.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Jun 2021; 237:34-44
Fujisaki T, Kuno T, Ando T, Briasoulis A, Takagi H, Bangalore S
Am Heart J: 29 Jun 2021; 237:34-44 | PMID: 33737060
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Impact:
Abstract

Rationale and design of the Women\'s Ischemia Trial to Reduce Events in Nonobstructive CAD (WARRIOR) trial.

Handberg EM, Merz CNB, Cooper-Dehoff RM, Wei J, ... Rogatko A, Pepine CJ
Background
Approximately half of all women with anginal symptoms and/or signs of ischemia and no obstructive coronary artery disease (INOCA) referred for coronary angiography have elevated risk for major adverse cardiac events (MACE), poor quality of life and resource consumption. Yet, guidelines focus on symptom management while clinical practice typically advocates only reassurance. Pilot studies of INOCA subjects suggest benefit with intensive medical therapy (IMT) that includes high-intensity statins and angiotensin converting enzyme inhibitors (ACE-I) or receptor blockers (ARB) to provide the rationale for a randomized pragmatic trial to limit MACE.
Methods
The Women\'s IschemiA TRial to Reduce Events In Non-ObstRuctive CAD is a multicenter, prospective, randomized, blinded outcome evaluation (PROBE design) of a pragmatic strategy of IMT vs usual care (UC) in 4,422 symptomatic women with INOCA (NCT03417388) in approximately 70 United States sites. The hypothesis is that IMT will reduce the primary outcome of first occurrence of MACE by 20% vs. UC at ∼2.5 year followup. Secondary outcomes include quality of life, time to return to \"duty\"/work, healthcare utilization, angina, cardiovascular death and individual primary outcome components over 3 years follow-up. The study utilizes web-based data capture, e-consents, single IRB and centralized pharmacy distribution of strategy medications directly to patients\' homes to reduce site and patient burden. A biorepository will collect blood samples to assess potential mechanisms.
Conclusions
The results of this trial will provide important data necessary to inform guidelines regarding how best to manage this growing and challenging population of women with INOCA.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Jun 2021; 237:90-103
Handberg EM, Merz CNB, Cooper-Dehoff RM, Wei J, ... Rogatko A, Pepine CJ
Am Heart J: 29 Jun 2021; 237:90-103 | PMID: 33745898
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Impact:
Abstract

Design and rationale of the randomized trial of comprehensive lifestyle modification, optimal pharmacological treatment and utilizing PET imaging for quantifying and managing stable coronary artery disease (the CENTURY study).

Kitkungvan D, Johnson NP, Kirkeeide R, Haynie M, ... Sdringola S, Gould KL
Background
The literature reports no randomized trial in chronic coronary artery disease (CAD) of a comprehensive management strategy integrating intense lifestyle management, maximal medical treatment to specific goals and high precision quantitative cardiac positron emission tomography (PET) for identifying high mortality risk patients needing essential invasive procedures. We hypothesize that this comprehensive strategy achieves greater risk factor reduction, lower major adverse cardiovascular events and fewer invasive procedures than standard practice.
Methods
The CENTURY Study (NCT00756379) is a randomized-controlled-trial study in patients with stable or at high risk for CAD. Patients are randomized to standard of care (Standard group) or intense comprehensive lifestyle-medical treatment to targets and PET guided interventions (Comprehensive group). Comprehensive Group patients are regularly consulted by the CENTURY team implementing diet/lifestyle/exercise program and medical treatment to target risk modification. Cardiac PET at baseline, 24-, and 60-months quantify the physiologic severity of CAD and guide interventions in the Comprehensive group while patients and referring physicians of the Standard group are blinded to PET results. The primary end-point is the CENTURY risk score reduction during 5 years follow-up. The secondary endpoint is a composite of death, non-fatal myocardial infarction, stroke, and coronary revascularization.
Conclusions
The CENTURY Study is the first study in stable CAD to test the incremental benefit of a comprehensive strategy integrating intense lifestyle modification, medical treatment to specific goals, and high-precision quantitative myocardial perfusion imaging to guide revascularization. A total of 1028 patients have been randomized, and the 5 years follow-up will conclude in 2022.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Jun 2021; 237:135-146
Kitkungvan D, Johnson NP, Kirkeeide R, Haynie M, ... Sdringola S, Gould KL
Am Heart J: 29 Jun 2021; 237:135-146 | PMID: 33762179
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Impact:
Abstract

A randomized prospective multicenter trial for stroke prevention by prophylactic surgical closure of the left atrial appendage in patients undergoing bioprosthetic aortic valve surgery--LAA-CLOSURE trial protocol.

Kiviniemi T, Bustamante-Munguira J, Olsson C, Jeppsson A, ... van Putte B, LAA-CLOSURE Investigators
Patients undergoing surgical aortic valve replacement (SAVR) are at high risk for atrial fibrillation (AF) and stroke after surgery. There is an unmet clinical need to improve stroke prevention in this patient population. The LAA-CLOSURE trial aims to assess the efficacy and safety of prophylactic surgical closure of the left atrial appendage for stroke and cardiovascular death prevention in patients undergoing bioprosthetic SAVR. This randomized, open-label, prospective multicenter trial will enroll 1,040 patients at 13 European sites. The primary endpoint is a composite of cardiovascular mortality, stroke and systemic embolism at 5 years. Secondary endpoints include cardiovascular mortality, stroke, systemic embolism, bleed fulfilling academic research consortium (BARC) criteria, hospitalization for decompensated heart failure and health economic evaluation. Sample size is based on 30% risk reduction in time to event analysis of primary endpoint. Prespecified reports include 30-day safety analysis focusing on AF occurrence and short-term outcomes and interim analyses at 1 and 3 years for primary and secondary outcomes. Additionally, substudies will be performed on the completeness of the closure using transesophageal echocardiography/cardiac computed tomography and long-term ECG recording at one year after the operation.

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

Am Heart J: 29 Jun 2021; 237:127-134
Kiviniemi T, Bustamante-Munguira J, Olsson C, Jeppsson A, ... van Putte B, LAA-CLOSURE Investigators
Am Heart J: 29 Jun 2021; 237:127-134 | PMID: 33798494
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Impact:
Abstract

Patient Characteristics, Care Patterns, and Outcomes of Atrial Fibrillation Associated Hospitalizations in Patients with Chronic Kidney Disease and End-Stage Renal Disease.

Kumar N, Xu H, Garg N, Pandey A, ... Lewis WR, Fonarow GC
Introduction
Chronic Kidney Disease (CKD) and end-stage renal disease (ESRD) are associated with poor outcomes in patients with cardiovascular disease. There is a paucity of contemporary data on in-hospital outcomes and care patterns of atrial fibrillation (AF) associated hospitalizations CKD and ESRD.
Methods
Outcomes and care patterns were evaluated in GWTG-AFIB database (Jan 2013-Dec 2018), including in-hospital mortality, use of a rhythm control strategy, and oral anticoagulation (OAC) prescription at discharge among eligible patients. Generalized logistic regression models with generalized estimating equations were used to ascertain differences in outcomes. Hospital-level variation in OAC prescription and rhythm control was also evaluated.
Results
Among 50,154 patients from 105 hospitals the median age was 70 years (interquartile range 61-79) and 47.3% were women. The prevalence of CKD was 36.0% while that of ESRD was 1.6%. Among eligible patients, discharge OAC prescription rates were 93.6% for CKD and 89.1% for ESRD. After adjustment, CKD and ESRD were associated with higher in-hospital mortality (odds ratio [OR] 3.08, 95% confidence interval [CI] 1.57-6.03 for ESRD and OR 2.02, 95% CI 1.52-2.67 for CKD), lower odds of OAC prescription at discharge (OR 0.59, 95% CI 0.44-0.79 for ESRD and OR 0.84, 95% CI 0.75-0.94 for CKD) compared with normal renal function. CKD was associated with lower utilization of rhythm control strategy (OR 0.92, 95% CI 0.87-0.98) with no significant difference between ESRD and normal renal function (OR 1.32, 95% CI 0.79-1.11). There was large hospital-level variation in OAC prescription at discharge (MOR 2.34, 95% CI 2.05-2.76) and utilization of a rhythm control strategy (MOR 2.69, 95% CI 2.34-3.21).
Conclusions
CKD/ESRD is associated with higher in-hospital mortality, less frequent rhythm control, and less OAC prescription among patients hospitalized for AF. There is wide hospital-level variation in utilization of a rhythm control strategy and OAC prescription at discharge highlighting potential opportunities to improve care and outcomes for these patients, and better define standards of care in this patient population.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 29 Jun 2021; epub ahead of print
Kumar N, Xu H, Garg N, Pandey A, ... Lewis WR, Fonarow GC
Am Heart J: 29 Jun 2021; epub ahead of print | PMID: 34216572
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Impact:
Abstract

Cardiovascular Procedural Deferral and Outcomes over COVID-19 Pandemic Phases: A Multi-Center Study.

Yong CM, Spinelli KJ, Chiu ST, Jones B, ... Heidenreich P, Gluckman TJ
Background
The COVID-19 pandemic has disrupted routine cardiovascular care, with unclear impact on procedural deferrals and associated outcomes across diverse patient populations.
Methods
Cardiovascular procedures performed at 30 hospitals across six Western states in two large, non-profit healthcare systems (Providence St. Joseph Health and Stanford Healthcare) from December 2018-June 2020 were analyzed for changes over time. Risk-adjusted in-hospital mortality was compared across pandemic phases with multivariate logistic regression.
Results
Among 36,125 procedures (69% percutaneous coronary intervention, 13% coronary artery bypass graft surgery, 10% transcatheter aortic valve replacement, and 8% surgical aortic valve replacement), weekly volumes changed in two distinct phases after the initial inflection point on February 23, 2020: an initial period of significant deferral (COVID I: March 15 to April 11) followed by recovery (COVID II: April 12 onwards). Compared to pre-COVID, COVID I patients were less likely to be female (p=0.0003), older (p<0.0001), Asian or Black (p=0.02), or Medicare insured (p<0.0001), and COVID I procedures were higher acuity (p<0.0001), but not higher complexity. In COVID II, there was a trend towards more procedural deferral in regions with a higher COVID-19 burden (p=0.05). Compared to pre-COVID, there were no differences in risk-adjusted in-hospital mortality during both COVID phases.
Conclusions
Significant decreases in cardiovascular procedural volumes occurred early in the COVID-19 pandemic, with disproportionate impacts by race, gender, and age. These findings should inform our approach to future healthcare disruptions.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 24 Jun 2021; epub ahead of print
Yong CM, Spinelli KJ, Chiu ST, Jones B, ... Heidenreich P, Gluckman TJ
Am Heart J: 24 Jun 2021; epub ahead of print | PMID: 34181910
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Impact:
Abstract

Randomized controlled trial of pErhexiline on regreSsion Of Left Ventricular hypErtrophy in patients with symptomatic Hypertrophic CardioMyopathy (RESOLVE-HCM Trial).

Ananthakrishna R, Lee SL, Foote J, Sallustio BC, ... Horowitz JD, Selvanayagam JB
Background
The presence and extent of left ventricular hypertrophy (LVH) is a major determinant of symptoms in patients with hypertrophic cardiomyopathy (HCM). There is increasing evidence to suggest that myocardial energetic impairment represents a central mechanism leading to LVH in HCM. There is currently a significant unmet need for disease-modifying therapy that regresses LVH in HCM patients. Perhexiline, a potent carnitine palmitoyl transferase-1 (CPT-1) inhibitor, improves myocardial energetics in HCM, and has the potential to reduce LVH in HCM.
Objective
The primary objective is to evaluate the effects of perhexiline treatment on the extent of LVH, in symptomatic HCM patients with at least moderate LVH.
Methods/design
RESOLVE-HCM is a prospective, multicentre double-blind placebo-controlled randomized trial enrolling symptomatic HCM patients with at least moderate LVH. Sixty patients will be randomized to receive either perhexiline or matching placebo. The primary endpoint is change in LVH, assessed utilising cardiovascular magnetic resonance (CMR) imaging, after 12-months treatment with perhexiline.
Summary
RESOLVE-HCM will provide novel information on the utility of perhexiline in regression of LVH in symptomatic HCM patients. A positive result would lead to the design of a Phase 3 clinical trial addressing long-term effects of perhexiline on risk of heart failure and mortality in HCM patients.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 23 Jun 2021; epub ahead of print
Ananthakrishna R, Lee SL, Foote J, Sallustio BC, ... Horowitz JD, Selvanayagam JB
Am Heart J: 23 Jun 2021; epub ahead of print | PMID: 34175315
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Impact:
Abstract

Relation of renal function to mid-term prognosis of stable angina patients with high- or low-dose pitavastatin treatment: REAL-CAD substudy.

Abe M, Ozaki Y, Takahashi H, Ishii M, ... Kimura T, Nagai R
Background
It has not yet been established whether higher-dose statins have beneficial effects on cardiovascular events in patients with stable coronary artery disease (CAD) and renal dysfunction.
Methods
The REAL-CAD study is a prospective, multicenter, open-label trial. As a substudy, we categorized patients by an estimated glomerular filtration rate (eGFR) as follows: eGFR ≥60 (n = 7,768); eGFR ≥45 and <60 (n = 3,176); and eGFR <45 mL/Min/1.73 m2 (n = 1,164), who were randomized to pitavastatin 4mg or 1mg therapy. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina, and was assessed by the log-rank test and Cox proportional hazards model.
Results
The baseline characteristics and medications were largely well-balanced between two groups. The magnitude of low-density lipoprotein cholesterol (LDL-C) reduction at 6 months in high- and low-dose pitavastatin groups was comparable among all eGFR categories. During a median follow-up of 3.9 years, high- compared with low-dose pitavastatin significantly reduced cardiovascular events in patients with eGFR ≥60 (hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.58-0.91; P = .006), and reduced but not significant for patients with eGFR ≥45 and <60 (HR 0.85; 95% CI, 0.63-1.14; P = .27) or eGFR <45 mL/Min/1.73 m2 (HR 0.90; 95% CI 0.62-1.33; P = .61). An interaction test of treatment by eGFR category was not significant (P value for interaction = .30).
Conclusion
Higher-dose pitavastatin therapy reduced LDL levels and cardiovascular events in stable CAD patients irrespective of eGFR level, although the effect on events appeared to be numerically lower in patients with lower eGFR.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 23 Jun 2021; 240:89-100
Abe M, Ozaki Y, Takahashi H, Ishii M, ... Kimura T, Nagai R
Am Heart J: 23 Jun 2021; 240:89-100 | PMID: 34174217
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Impact:
Abstract

Infective endocarditis and solid organ transplantation: Only worse outcomes during initial transplantation hospitalization.

Eichenberger EM, Dagher M, Sinclair MR, Maskarinec SA, Fowler VG, Federspiel JJ
Background
The epidemiology, and outcome of infective endocarditis (IE) among solid organ transplant (SOT) recipients is unknown.
Methods
We used data from the 2013-2018 Nationwide Readmissions Database (NRD). IE- and SOT-associated hospitalizations were identified using diagnosis and procedure codes. Outcomes included inpatient mortality, length of stay, and inpatient costs. Adjusted analyses were performed using weighted regression models.
Results
A total of 99,052 IE-associated hospitalizations, corresponding to a weighted national estimate of 193,164, were included for analysis. Of these, 794 (weighted n = 1,574) were associated with transplant history (SOT-IE). Mortality was not significantly different between SOT-IE and non-SOT-IE (17.2% vs. 15.8%, adjusted relative risk [aRR]: 0.86, 95% confidence interval [CI] [0.71, 1.03]), and fewer SOT-IE patients underwent valve repair or replacement than non-SOT-IE (12.5% vs. 16.2%, aRR 0.82, 95% CI [0.71, 0.95]). We then compared outcomes of patients diagnosed with IE during their index transplant hospitalization (index-SOT-IE) to patients without IE during their transplant hospitalization (index-SOT). Index-SOT-IE occurred most frequently among heart transplant recipients (45.1%), and was associated with greater mortality (27.1% vs. 2.3%, aRR 6.07, 95% CI [3.32, 11.11]).
Conclusion
Dual diagnosis of SOT and IE was associated with worse outcomes among SOT recipients during index hospitalization, but not overall among patients with IE.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 19 Jun 2021; 240:63-72
Eichenberger EM, Dagher M, Sinclair MR, Maskarinec SA, Fowler VG, Federspiel JJ
Am Heart J: 19 Jun 2021; 240:63-72 | PMID: 34157299
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Impact:
Abstract

Association between Symptoms, Affect and Heart Rhythm in Patients with Persistent or Paroxysmal Atrial Fibrillation: An Ambulatory Pilot Study.

Wheelock KM, Kratz A, Lathkar-Pradhan S, Najarian K, ... Nallamothu BK, Ghanbari H
Symptoms in atrial fibrillation are generally assumed to correspond to heart rhythm; however, patient affect - the experience of feelings, emotion or mood - is known to frequently modulate how patients report symptoms but this has not been studied in atrial fibrillation. In this study, we investigated the relationship between affect, symptoms and heart rhythm in patients with paroxysmal or persistent atrial fibrillation. We found that presence of negative affect portended reporting of more severe symptoms to the same or greater extent than heart rhythm.

Copyright © 2021 Elsevier Ltd. All rights reserved.

Am Heart J: 18 Jun 2021; epub ahead of print
Wheelock KM, Kratz A, Lathkar-Pradhan S, Najarian K, ... Nallamothu BK, Ghanbari H
Am Heart J: 18 Jun 2021; epub ahead of print | PMID: 34157300
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Impact:
Abstract

The challenge of sustainability: Long-term results from the Fifty-Fifty peer group-based intervention in cardiovascular risk factors.

Fernández-Alvira JM, Fernández-Jiménez R, de Miguel M, Santos-Beneit G, ... Robledo T, Fuster V
Background
The Fifty-Fifty trial demonstrated that a peer-group-based intervention was able to improve healthy behaviors in individuals with cardiovascular (CV) risk factors immediately post-intervention.
Objectives
To determine the long-term sustainability of a one-year peer-group-based intervention focused on CV health and behavior.
Methods
A total of 543 adults aged 25 to 50 years with at least 1 CV risk factor were screened and recruited, received initial training through workshops, and were then randomized 1:1 to a peer-group-based intervention group (IG) or a self-management control group (CG) for 12 months. At a median of 52 months from baseline, 321 participants were re-assessed (~60% retention). The primary outcome was the mean change in a composite health score related to blood pressure, exercise, weight, alimentation, and tobacco use (Fuster-BEWAT score [FBS], range 0-15). Intervention effects were assessed using linear-mixed effects models.
Results
The mean age of retained participants was 48.0 years (SD: 5.4), and 73% were female. Consistent with previous results, the change of overall FBS was significantly greater in the IG than in the CG at 12-month follow-up (between-group difference, 0.60 points; 95% CI, 0.08-1.12; P = .025). Assessment of long-term sustainability (52-month follow-up) showed that there were no between-group differences in the mean overall FBS (IG mean score, 8.52; 95% CI, 7.97-9.07 vs CG mean score, 8.51; 95% CI, 7.93-9.10; P = .972) or in the change of overall FBS from screening (IG mean change, 0.64; 95% CI, 0.00-1.28; CG mean change, 0.46; 95% CI, -0.20-1.12; P = .497).
Conclusions
A one-year peer-group-based intervention showed favorable results at immediate post-intervention but did not demonstrate significant differences between the IG and CG at 52 months. Combination of an initial training period (workshops) with the maintenance of peer-support groups or other re-intervention strategies may be required to achieve sustained effects on healthy behaviors.
Trial registration
ClinicalTrials.gov identifier NCT02367963. Registered (https://clinicaltrials.gov/show/NCT02367963).

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 17 Jun 2021; 240:81-88
Fernández-Alvira JM, Fernández-Jiménez R, de Miguel M, Santos-Beneit G, ... Robledo T, Fuster V
Am Heart J: 17 Jun 2021; 240:81-88 | PMID: 34147462
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Impact:
Abstract

Renin-angiotensin-aldosterone system inhibitors and SARS-CoV-2 infection: an analysis from the veteran\'s affairs healthcare system.

Sandhu AT, Kohsaka S, Lin S, Woo CY, Goldstein MK, Heidenreich PA
Background
Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are known to impact the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The association between chronic therapy with these medications and infection risk remains unclear.
Objectives
The objective was to determine the association between prior ACEI or ARB therapy and SARS-CoV-2 infection among patients with hypertension in the U.S. Veteran\'s Affairs health system.
Methods
We compared the odds of SARS-CoV-2 infection among three groups: patients treated with ACEI, treated with ARB, or treated with alternate first-line anti-hypertensives without ACEI/ARB. We excluded patients with alternate indications for ACEI or ARB therapy. We performed an augmented inverse propensity weighted analysis with adjustment for demographics, region, comorbidities, vitals, and laboratory values.
Results
Among 1,724,723 patients with treated hypertension, 659,180 were treated with ACEI, 310,651 with ARB, and 754,892 with neither. Before weighting, patients treated with ACEI or ARB were more likely to be diabetic and use more anti-hypertensives. There were 13,278 SARS-CoV-2 infections (0.8%) between February 12, 2020 and August 19, 2020. Patients treated with ACEI had lower odds of SARS-CoV-2 infection (odds ratio [OR] 0.93; 95% CI: 0.89-0.97) while those treated with ARB had similar odds (OR 1.02; 95% CI: 0.96-1.07) compared with patients treated with alternate first-line anti-hypertensives without ACEI/ARB. In falsification analyses, patients on ACEI did not have a difference in their odds of unrelated outcomes.
Conclusions
Our results suggest the safety of continuing ACEI and ARB therapy. The association between ACEI therapy and lower odds of SARS-CoV-2 infection requires further investigation.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 11 Jun 2021; 240:46-57
Sandhu AT, Kohsaka S, Lin S, Woo CY, Goldstein MK, Heidenreich PA
Am Heart J: 11 Jun 2021; 240:46-57 | PMID: 34126079
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Impact:
Abstract

Association of kidney function and atrial fibrillation progression to clinical outcomes in patients with cardiac implantable electronic devices.

Szummer K, Perino AC, Fan J, Kothari M, Turakhia MP
Background
Kidney function may promote progression of AF.
Objective
We evaluated the association of kidney function to AF progression and resultant clinical outcomes in patients with cardiac implantable electronic devices (CIED).
Methods
We performed a retrospective cohort study using national clinical data from the Veterans Health Administration linked to CIED data from the Carelink® remote monitoring data warehouse (Medtronic Inc, Mounds View, MN). All devices had atrial leads and at least 75% of remote monitoring transmission coverage. Patients were included at the date of the first AF episode lasting ≥6 minutes, and followed until the occurrence of persistent AF in the first year, defined as ≥7 consecutive days with continuous AF. We used Cox regression analyses with persistent AF as a time-varying covariate to examine the association to stroke, myocardial infarction, heart failure and death.
Results
Of, 10,323 eligible patients, 1,771 had a first CIED-detected AF (mean age 69 ± 10 years, 1.2% female). In the first year 355 (20%) developed persistent AF. Kidney function was not associated with persistent AF after multivariable adjustment including CHA2DS2-VASc variables and prior medications. Only higher age increased the risk (HR: 1.28 per 10 years; 1.07-1.52). Persistent AF was associated to higher risk of heart failure (HR: 2.27; 95% CI: 1.88-2.74) and death (HR: 1.60; 95% CI: 1.30-1.96), but not stroke (HR: 1.28; 95% CI: 0.62-2.62) or myocardial infarction (HR: 1.43; 95% CI: 0.91-2.25).
Conclusion
Kidney function was not associated to AF progression, whereas higher age was. Preventing AF progression could reduce the risk of heart failure and death.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 08 Jun 2021; epub ahead of print
Szummer K, Perino AC, Fan J, Kothari M, Turakhia MP
Am Heart J: 08 Jun 2021; epub ahead of print | PMID: 34118202
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Impact:
Abstract

Regional variation of effects of new antidiabetic medications in cardiovascular outcome trials.

Cotter G, Davison BA, Edwards C, Senger S, ... Sato N, Cohen-Solal A
Background
In international trials, glucagon-like protein-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2Is) were effective in improving cardiovascular (CV) outcomes.
Methods
We assessed the effect of GLP-1RAs and SGLT2Is treatment effect on CV endpoints by geographical region in multiple international trials using random effects weighted least squares meta-regressions.
Results
The estimated effects of both SGLT2Is and GLP-1RAs on major adverse CV events (MACE) in North America (SGLT2Is n = 12,399, HR 0.90, 95% CI 0.81-1.01; GLP-1RAs n = 12,515, HR 0.95, 95% CI 0.83- 1.09) and in Europe (SGLT2Is n = 19,435, HR 0.93, 95% CI 0.85-1.02; GLP-1RAs n = 22,812, HR 0.88, 95% CI 0.79-0.99) were numerically lower but not statistically different to the rest of the world (ROW) (SGLT2Is n = 15,127, HR 0.83, 95% CI 0.75-0.92, p-value for interaction 0.26; GLP-1RAs n = 17,494, HR 0.82, 95% CI 0.73-0.92, p-value for interaction 0.28). Effects of SGLT2Is on heart failure readmission or CV death varied significantly by region (P = 0.0094). The effect of SGLT2Is was significantly smaller in Europe (n = 18,653, HR 0.86, 95% CI 0.78-0.95) than in the ROW (n = 12,463, HR 0.68, 95% CI 0.61-0.76, P = 0.0024). The smaller effect in North America (n = 9776, HR 0.76, 95% CI 0.66-0.87) did not differ significantly from that in the ROW (P = 0.2370).
Conclusion
The effects of SGLT2Is on HF events are larger in the ROW. Further analyses and studies are needed to better elucidate the differential effects of SGLTIs and GLP-1RAs by geographical regions.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 05 Jun 2021; 240:73-80
Cotter G, Davison BA, Edwards C, Senger S, ... Sato N, Cohen-Solal A
Am Heart J: 05 Jun 2021; 240:73-80 | PMID: 34107289
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Impact:
Abstract

Mental health disorders and emergency resource use and outcomes in ventricular assist device supported patients.

Edwards JJ, Edelson JB, Katcoff H, Mondal A, ... Lin KY, Birati EY
There are limited data describing the prevalence of mental health disorders (MHDOs) in patients with ventricular assist devices (VADs), or associations between MHDOs and resource use or outcomes. We used the Nationwide Emergency Department Sample administrative database to analyze 44,041 ED encounters for VAD-supported adults from 2010 to 2017, to assess the relationship between MHDOs and outcomes in this population. MHDO diagnoses were present for 23% of encounters, and were associated with higher charges and rates of admission, but lower mortality.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 02 Jun 2021; 240:11-15
Edwards JJ, Edelson JB, Katcoff H, Mondal A, ... Lin KY, Birati EY
Am Heart J: 02 Jun 2021; 240:11-15 | PMID: 34089695
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Impact:
Abstract

Sociodemographic differences in utilization and outcomes for temporary cardiovascular mechanical support in the setting of cardiogenic shock.

Thangam M, Luke AA, Johnson DY, Amin AP, ... Huang K, Joynt Maddox KE
Background
Temporary mechanical circulatory support (MCS) devices are increasingly used in cardiogenic shock, but whether sociodemographic differences by sex, race and/or ethnicity, insurance status, and neighborhood poverty exist in the utilization of these devices is unknown.
Methods
Retrospective cross-sectional study using the National Inpatient Sample for 2012-2017. Logistic regression models were used to examine predictors of use of temporary MCS devices and for in-hospital mortality, clustering by hospital-year.
Results
Our study population included 109,327 admissions for cardiogenic shock. Overall, 14.3% of admissions received an intra-aortic balloon pump, 4.2% a percutaneous ventricular assist device, and 1.8% extracorporeal membranous oxygenation (ECMO). After adjusting for age, comorbidities, and hospital characteristics, use of temporary MCS was lower in women compared to men (adjusted odds ratio [aOR] = 0.76, P < .001), Black patients compared to white ones (aOR = 0.73, P < .001), those insured by Medicare (aOR = 0.75, P < .001), Medicaid (aOR = 0.74, P < .001), or uninsured (aOR = 0.90, P = .015) compared to privately insured, and those in the lowest income neighborhoods (aOR = 0.94, P = .003) versus other neighborhoods. Women, admissions covered by Medicare, Medicaid, or uninsured, and those from low-income neighborhoods also had higher mortality rates even after adjustment for MCS implantation.
Conclusions
There are differences in the use of temporary MCS in the setting of cardiogenic shock among specific populations within the United States. The growing use of MCS for treating cardiogenic shock highlights the need to better understand its impact on outcomes.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 30 May 2021; 236:87-96
Thangam M, Luke AA, Johnson DY, Amin AP, ... Huang K, Joynt Maddox KE
Am Heart J: 30 May 2021; 236:87-96 | PMID: 33359779
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Impact:
Abstract

Rivaroxaban versus warfarin in patients with atrial fibrillation enrolled in Latin America: Insights from ROCKET AF.

Blumer V, Rivera M, Corbalán R, Becker RC, ... Fox KAA, Patel MR
Background
ROCKET AF demonstrated the efficacy and safety of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism (SE) in patients with atrial fibrillation (AF). We examined baseline characteristics and outcomes in patients enrolled in Latin America compared with the rest of the world (ROW).
Methods
ROCKET AF enrolled 14,264 patients from 45 countries. Of these, 1,878 (13.2%) were from 7 Latin American countries. The clinical characteristics and outcomes (adjusted by baseline characteristics) of these patients were compared with 12,293 patients from the ROW. Treatment outcomes of rivaroxaban compared with warfarin were also stratified by region.
Results
The annual rate of stroke/SE was similar in those from Latin American and ROW (P= .63), but all-cause and vascular death were significantly higher than in ROW (HR 1.40, 95% CI 1.20-1.64; HR 1.38, 95% CI 1.14-1.68; P< .001). Rates of major or nonmajor clinically relevant bleeding tended to be lower in Latin America (HR 0.89, 95% CI 0.80-1.0; P= .05). Rates of stroke and/or SE were similar with rivaroxaban and warfarin in patients from Latin America and ROW (HR 0.83, 95% CI 0.54-1.29 vs HR 0.89, 95% CI 0.75-1.07; interaction P= .77).
Conclusions
Patients with AF in Latin America had similar rates of stroke and/or SE, higher rates of vascular death, and lower rates of bleeding compared with patients in the ROW. The effect of rivaroxaban compared with warfarin in Latin America was similar to the ROW. Further studies analyzing patient- and country-specific determinants of these regional differences in Latin America are warranted.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 30 May 2021; 236:4-12
Blumer V, Rivera M, Corbalán R, Becker RC, ... Fox KAA, Patel MR
Am Heart J: 30 May 2021; 236:4-12 | PMID: 33571477
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Impact:
Abstract

Cardiac transplantation outcomes in patients with amyloid cardiomyopathy.

Ohiomoba RO, Youmans QR, Ezema A, Akanyirige P, ... Yancy CW, Okwuosa IS
Objective
Amyloid cardiomyopathy (ACM) is a progressive and life-threatening disease caused by abnormal protein deposits within cardiac tissue. The most common forms of ACM are caused by immunoglobulin derived light chains (AL) and transthyretin (TTR). Orthotopic heart transplantation (OHT) remains the definitive treatment for patients with end stage heart failure. In this study, we perform a contemporary multicenter analysis evaluating post OHT survival in patients with ACM.
Methods
We conducted a multicenter analysis of 40,044 adult OHT recipients captured in the United Network for Organ Sharing (UNOS) registry from 1987-2018. Patients were characterized as ACM or non-ACM. Baseline characteristics were obtained, and summary characteristics were calculated. Outcomes of interest included post-transplant survival, infection, treated rejection, and the ability to return to work. Racial differences in OHT survival were also analyzed. Unadjusted associations between ACM and non-ACM survival were determined using the Kaplan-Meier estimations and confounding was addressed using multivariable Cox proportional hazards models.
Results
Three hundred ninety-eight patients with a diagnosis of ACM were identified of which 313 underwent heart only OHT. ACM patients were older (61 vs 53; P < .0001) and had a higher proportion of African Americans (30.7% vs 17.6%; P < .0001). Median survival for ACM was 10.2 years vs 12.5 years in non-ACM (P = .01). After adjusting for confounding, ACM patients had a higher likelihood of death post-OHT (HR 1.39 CI: 1.14, 1.70; P = .001). African American ACM patients had a higher likelihood of survival compared to White ACM patients (HR 0.51 CI 0.31-0.85; P = .01). No difference was observed in episodes of treated rejection (OR 0.63 CI 0.23, 1.78; P = .39), hospitalizations for infections (OR 1.24 CI: 0.85, 1.81; P = .26), or likelihood of returning to work for income (OR 1.23 CI: 0.84, 1.80; P = .30).
Conclusions
In this analysis of OHT in ACM, ACM was associated with a higher likelihood of post-OHT mortality. Racial differences in post-OHT were observed with African American patients with ACM having higher likelihood of survival compared to White patients with ACM. No differences were observed in episodes of treated rejection, hospitalization for infection, or likelihood to return to work for income.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 May 2021; 236:13-21
Ohiomoba RO, Youmans QR, Ezema A, Akanyirige P, ... Yancy CW, Okwuosa IS
Am Heart J: 30 May 2021; 236:13-21 | PMID: 33621542
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Impact:
Abstract

Comparison of one-month versus twelve-month dual antiplatelet therapy after implantation of drug-eluting stents guided by either intravascular ultrasound or angiography in patients with acute coronary syndrome: rationale and design of prospective, multicenter, randomized, controlled IVUS-ACS and ULTIMATE-DAPT trial.

Ge Z, Gao XF, Kan J, Kong XQ, ... Zhang JJ, Chen SL
Background
Current guidelines recommend administering dual antiplatelet therapy (DAPT) for 12 months to patients with acute coronary syndromes (ACS) and without contraindications after drug-eluting stent (DES) implantation. A recent study reported that 3 months of DAPT followed by ticagrelor monotherapy is effective and safe in ACS patients undergoing DES implantation compared with the standard duration of DAPT. However, it is unclear whether antiplatelet monotherapy with ticagrelor alone versus ticagrelor plus aspirin reduces the incidence of clinically relevant bleeding without increasing the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in ACS patients undergoing percutaneous coronary intervention (PCI) with DES implantation guided by either intravascular ultrasound (IVUS) or angiography who have completed a 1-month course of DAPT with aspirin plus ticagrelor.
Methods
The IVUS-ACS and ULTIMATE-DAPT is a prospective, multicenter, randomized, controlled trial designed to determine (1) whether IVUS-guided versus angiography-guided DES implantation in patients with ACS reduces the risk of target vessel failure (TVF) at 12 months and (2) whether ticagrelor alone versus ticagrelor plus aspirin reduces the risk of clinically relevant bleeding without increasing the risk of MACCE 1-12 months after the index PCI in ACS patients undergoing DES implantation guided by either IVUS or angiography. This study will enroll 3486 ACS patients eligible for DES implantation, as confirmed by angiographic studies. The patients who meet the inclusion criteria and none of the exclusion criteria will be randomly assigned in a 1:1 fashion to the IVUS- or angiography-guided group (first randomization). All enrolled patients will complete a 1-month course of DAPT with aspirin plus ticagrelor after the index PCI. Patients with no MACCEs or major bleeding (≥Bleeding Academic Research Consortium (BARC) 3b) within 30 days will be randomized in a 1:1 fashion to either the ticagrelor plus matching placebo (SAPT)group or ticagrelor plus aspirin (DAPT)group for an additional 11 months (second randomization). The primary endpoint of the IVUS-ACS trial is TVF at 12 months, including cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target vessel revascularization (CD-TVR). The primary superiority endpoint of the ULTIMATE-DAPT trial is clinically relevant bleeding, defined as BARC Types 2, 3, or 5 bleeding, and the primary non-inferiority endpoint of the ULTIMATE-DAPT trial is MACCE, defined as cardiac death, myocardial infarction, ischemic stroke, CD-TVR, or definite stent thrombosis occurring 1-12 months in the second randomized population.
Conclusion
The IVUS-ACS and ULTIMATE-DAPT trial is designed to test the efficacy and safety of 2 different antiplatelet strategies in ACS patients undergoing PCI with DES implantation guided by either IVUS or angiography. This study will provide novel insights into the optimal DAPT duration in ACS patients undergoing PCI and provide evidence on the clinical benefits of IVUS-guided PCI in ACS patients.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 May 2021; 236:49-58
Ge Z, Gao XF, Kan J, Kong XQ, ... Zhang JJ, Chen SL
Am Heart J: 30 May 2021; 236:49-58 | PMID: 33621541
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Impact:
Abstract

Plasma trimethylamine N-oxide (TMAO) levels predict future risk of coronary artery disease in apparently healthy individuals in the EPIC-Norfolk prospective population study.

Tang WHW, Li XS, Wu Y, Wang Z, ... Boekholdt SM, Hazen SL
Background
Recent studies show a mechanistic link between gut microbiota-dependent formation of the atherosclerosis- and thrombosis-promoting metabolite trimethylamine N-oxide (TMAO) and cardiovascular disease (CVD). The clinical utility of TMAO in apparently healthy subjects for predicting incident CVD risks is unclear.
Methods and results
In the EPIC-Norfolk community-based study, we examined baseline fasting levels of TMAO and two of its nutrient precursors, choline and betaine, in a case:control design study comparing apparently European healthy middle-aged participants who subsequently develop CVD (Cases, n = 908) vs those who did not (Controls, n = 1,273) over an ensuing average follow-up period of 8 years. In participants who developed CVD vs controls, higher plasma TMAO (3.70 [IQR 2.50-6.41]μM vs 3.25 [IQR 2.19-52,1.15]μM; P < .001) and choline levels (9.09 [IQR 7.87-10.53]μM vs 8.89 [IQR 7.66-10.13]μM; P = .001) were observed. Following adjustments for traditional risk factors, elevated TMAO (adjusted odds ratio (OR) 1.58 [95% confidence interval (CI) 1.21-2.06], P < .001) and choline levels (adjusted OR 1.31 [95%CI 1.00-1.72], P < .05) remained predictive of incident CVD development. The clinical prognostic utility of TMAO remained significant and essentially unchanged regardless of the level of cutoff chosen between 1.5 uM (10%ile) to 10.5 uM (90%ile).
Conclusion
In apparently healthy participants of the community-based middle-aged EPIC-Norfolk population, elevated plasma levels of the gut microbe-dependent metabolite TMAO, and its nutrient precursor choline, predict incident risk for CVD development independent of traditional risk factors.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 May 2021; 236:80-86
Tang WHW, Li XS, Wu Y, Wang Z, ... Boekholdt SM, Hazen SL
Am Heart J: 30 May 2021; 236:80-86 | PMID: 33626384
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Impact:
Abstract

Does study subject diversity influence cardiology research site performance?: Insights from 2 U.S. National Coronary Stent Registries.

Batchelor WB, Damluji AA, Yong C, Fiuzat M, ... O\'Connor CM, Mehran R
Background
Minorities and women are underrepresented in cardiovascular research. Whether their higher enrollment can be predicted or influences research site performance is unclear.
Methods
We evaluated 104 sites that enrolled 4,184 patients in the U.S. Platinum Diversity (PD) and Promus Element Plus (PE Plus) studies (2012 to 2016). Research sites were ranked from lowest to highest minority and female enrollment, respectively. United States Census Bureau division and core-based statistical area (CBSA) populations were determined for each site and the following study performance metrics compared across quartiles of minority and female enrollment, respectively: (1) study subject enrollment rate (SER), (2) time to first patient enrolled, (3) rate of follow-up visits not done, (4) rate of follow-up visits out of window, and (5) protocol deviation rate (PDR). Multivariable regression was used to predict SER and PDR.
Results
Minority enrollment varied by region (P = .025) and population (P = .024) with highest recruitment noted in the Pacific, West South Central, South Atlantic, Mid-Atlantic and East North Central divisions. Female enrollment bore no relationship to region (P = .67) or population (P = .40). Median SER was similar in sites withi the highest vs lowest quartile of minority enrollment (SER of 4 vs 5 patients per month, respectively, P =0.78) and highest vs. lowest female enrollment (SER of 4 vs 4, respectively, P = .21). Median PDR was lower in sites within the highest vs lowest minority enrollment (0.23 vs 0.50 PDs per patient per month, respectively, P = .01) and highest vs. lowest female enrollment (0.28 vs. 0.37 PDs per patient per month, respectively, P = .04). However, this relationship did not persist after multivariable adjustment. All other site performance metrics were comparable across quartiles of minority and female enrollment.
Conclusions
Minority, but not female enrollment, correlated with research site geographic region and surrounding population. High enrollment of minorities and women did not influence study performance metrics. These findings help inform future strategies aimed at increasing clinical trial diversity.
Trial registration
The PD and PE Plus studies are registered at www.clinicaltrials.gov under identifiers NCT02240810 and NCT01589978, respectively.
Key points
Question: Does the enrollment of more Blacks, Hispanics and women in US cardiovascular research studies influence the overall rate of study subject enrollment and/or other key study site performance metrics and can diverse enrollment be predicted?
Findings
In this pooled analysis of 104 sites that enrolled 4,184 patients in the Platinum Diversity and Promus Element Plus Post-Approval Studies, we found that the enrollment of higher proportions of underrepresented minorities and women was univariately associated with lower protocol deviation rates while having no effect on other site performance metrics. A site\'s geographic location and surrounding population predicted minority, but not female enrollment. Meaning: These findings suggest that cardiovascular research subject diversity may be predicted from site characteristics and enhanced without compromising key study performance metrics. These insights help inform future strategies aimed at improving clinical trial diversity.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 May 2021; 236:37-48
Batchelor WB, Damluji AA, Yong C, Fiuzat M, ... O'Connor CM, Mehran R
Am Heart J: 30 May 2021; 236:37-48 | PMID: 33636137
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Impact:
Abstract

Access to cardiac surgery centers for cardiac and non-cardiac hospitalizations in adolescents and adults with congenital heart defects- a descriptive case series study.

Insaf TZ, Sommerhalter KM, Jaff TA, Farr SL, ... Lui GK, Van Zutphen AR
Background
Individuals with congenital heart defects (CHDs) are recommended to receive all inpatient cardiac and noncardiac care at facilities that can offer specialized care. We describe geographic accessibility to such centers in New York State and determine several factors associated with receiving care there.
Methods
We used inpatient hospitalization data from the Statewide Planning and Research Cooperative System (SPARCS) in New York State 2008-2013. In the absence of specific adult CHD care center designations during our study period, we identified pediatric/adult and adult-only cardiac surgery centers through the Cardiac Surgery Reporting System to estimate age-based specialized care. We calculated one-way drive and public transit time (in minutes) from residential address to centers using R gmapsdistance package and the Google Maps Distance Application Programming Interface (API). We calculated prevalence ratios using modified Poisson regression with model-based standard errors, fit with generalized estimating equations clustered at the hospital level and subclustered at the individual level.
Results
Individuals with CHDs were more likely to seek care at pediatric/adult or adult-only cardiac surgery centers if they had severe CHDs, private health insurance, higher severity of illness at encounter, a surgical procedure, cardiac encounter, and shorter drive time. These findings can be used to increase care receipt (especially for noncardiac care) at pediatric/adult or adult-only cardiac surgery centers, identify areas with limited access, and reduce disparities in access to specialized care among this high-risk population.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Am Heart J: 30 May 2021; 236:22-36
Insaf TZ, Sommerhalter KM, Jaff TA, Farr SL, ... Lui GK, Van Zutphen AR
Am Heart J: 30 May 2021; 236:22-36 | PMID: 33636136
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Impact:
Abstract

Total vascular resistance increases during volume-unloading in asymptomatic single ventricle patients.

Vaiyani D, Matsuo K, Kanaan U, Patel B, ... Sachdeva R, Petit CJ
Objective
While the surgical stages of single ventricle (SV) palliation serve to separate pulmonary venous and systemic venous return, and to volume-unload the SV, staged palliation also results in transition from parallel to series circulation, increasing total vascular resistance. How this transition affects pressure loading of the SV is as yet unreported.
Methods
We performed a retrospective chart review of Stage I, II, and III cardiac catheterization (CC) and echocardiographic data from 2001-2017 in all SV pts, with focus on systemic, pulmonary, and total vascular resistance (SVR, PVR, TVR respectively). Longitudinal analyses were performed with log-transformed variables. Effects of SVR-lowering medications were analyzed using Wilcoxon rank-sum testing.
Results
There were 372 total patients who underwent CC at a Stage I (median age of 4.4 months, n=310), Stage II (median age 2.7 years, n = 244), and Stage III (median age 7.3 years, n = 113). Total volume loading decreases with progression to Stage III (P< 0.001). While PVR gradually increases from Stage II to Stage III, and SVR increases from Stage I to Stage III, TVR dramatically increases with progress towards series circulation. TVR was not affected by use of systemic vasodilator therapy. TVR, PVR, SVR, and CI did not correlate with indices of SV function at Stage III.
Conclusions
TVR steadily increases with an increasing contribution from SVR over progressive stages. TVR was not affected by systemic vasodilator agents. TVR did not correlate with echo-based indices of SV function. Further studies are needed to see if modulating TVR can improve exercise tolerance and outcomes.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 May 2021; 236:69-79
Vaiyani D, Matsuo K, Kanaan U, Patel B, ... Sachdeva R, Petit CJ
Am Heart J: 30 May 2021; 236:69-79 | PMID: 33640333
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Impact:
Abstract

Rivaroxaban monotherapy versus combination therapy according to patient risk of stroke and bleeding in atrial fibrillation and stable coronary disease: AFIRE trial subanalysis.

Akao M, Yasuda S, Kaikita K, Ako J, ... Matsui K, Ogawa H
Background
In the AFIRE trial, rivaroxaban monotherapy was noninferior to combination therapy with rivaroxaban and an antiplatelet agent for thromboembolic events or death, and superior for major bleeding in patients with atrial fibrillation (AF) and stable coronary artery disease. Little is known about impacts of stroke and bleeding risks on the efficacy and safety of rivaroxaban monotherapy.
Methods
In this subanalysis of the AFIRE trial, we assessed the risk of stroke and bleeding by the CHADS2, CHA2DS2-VASc, and HAS-BLED scores. The primary efficacy end point was the composite of stroke, systemic embolism, myocardial infarction (MI), unstable angina requiring revascularization, or death from any cause. The primary safety end point was major bleeding defined by the International Society on Thrombosis and Haemostasis.
Results
Rivaroxaban monotherapy significantly reduced the primary efficacy and safety end points with no evidence of differential effects by stroke risk (CHADS2, p for interaction = 0.727 for efficacy, 0.395 for safety; CHA2DS2-VASc, p for interaction = 0.740 for efficacy, 0.265 for safety) or bleeding risk (HAS-BLED, p for interaction = 0.581 for efficacy, 0.225 for safety). There was also no evidence of statistical heterogeneity across patient risk categories for other end points; stroke or systemic embolism, ischemic stroke, hemorrhagic stroke, MI, MI or unstable angina, death from any cause, any bleeding, or net adverse clinical events.
Conclusions
The advantages of rivaroxaban monotherapy compared with those of combination therapy with respect to all prespecified end points, including thromboembolism, bleeding, and mortality were similar across patients with AF and stable coronary artery disease, irrespective of their risk for stroke and bleeding.
Clinical trial registration
UMIN Clinical Trials Registry number, UMIN000016612, and ClinicalTrials.gov number, NCT02642419.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 30 May 2021; 236:59-68
Akao M, Yasuda S, Kaikita K, Ako J, ... Matsui K, Ogawa H
Am Heart J: 30 May 2021; 236:59-68 | PMID: 33657403
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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 May 2021; 240:28-45
Bajaj R, Parasa R, Ramasamy A, Makariou N, ... Baumbach A, Bourantas CV
Am Heart J: 29 May 2021; 240:28-45 | PMID: 34077744
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Impact:
Abstract

Cardiac rehabilitation availability and characteristics in Latin America and the Caribbean: A Global Comparison.

Chacin-Suarez A, Grace SL, Anchique-Santos C, Supervia M, ... Medina-Inojosa JR, Lopez-Jimenez F
Background
This study aimed to establish availability and characteristics of cardiac rehabilitation (CR) in Latin America and the Caribbean (LAC), where cardiovascular disease is highly prevalent.
Methods
In this cross-sectional sub-analysis focusing on the 35 LAC countries, local cardiovascular societies identified CR programs globally. An online survey was administered to identified programs, assessing capacity and characteristics. CR need was computed relative to ischemic heart disease (IHD) incidence from the Global Burden of Disease study.
Results
≥1 CR program was identified in 24 LAC countries (68.5% availability; median = 3 programs/country). Data were collected in 20/24 countries (83.3%); 139/255 programs responded (54.5%), and compared to responses from 1082 programs in 111 countries. LAC density was 1 CR spot per 24 IHD patients/year (vs 18 globally). Greatest need was observed in Brazil, Dominican Republic and Mexico (all with >150,000 spots needed/year). In 62.8% (vs 37.2% globally P < .001) of CR programs, patients pay out-of-pocket for some or all of CR. CR teams were comprised of a mean of 5.0 ± 2.3 staff (vs 6.0 ± 2.8 globally; P < .001); Social workers, dietitians, kinesiologists, and nurses were significantly less common on CR teams than globally. Median number of core components offered was 8 (vs 9 globally; P < .001). Median dose of CR was 36 sessions (vs 24 globally; P < .001). Only 27 (20.9%) programs offered alternative CR models (vs 31.1% globally; P < .01).
Conclusion
In LAC countries, there is very limited CR capacity in relation to need. CR dose is high, but comprehensiveness low, which could be rectified with a more multidisciplinary team.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 27 May 2021; 240:16-27
Chacin-Suarez A, Grace SL, Anchique-Santos C, Supervia M, ... Medina-Inojosa JR, Lopez-Jimenez F
Am Heart J: 27 May 2021; 240:16-27 | PMID: 34058163
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Impact:
Abstract

Use of oral anticoagulants in patients with valvular atrial fibrillation: findings from the NCDR PINNACLE Registry.

Hess PL, Gosch KL, Jani SM, Varosy PD, ... Michael Ho P, Virani SS
Recent data suggest direct oral anticoagulants are as safe and efficacious as warfarin among select patients with valvular heart disease and atrial fibrillation (AF). However, real-world treatment patterns of AF stroke prophylaxis in the setting of valvular AF are currently unknown. Accordingly, using the prospective, ambulatory National Cardiovascular Data Registry Practice Innovation and Clinical Excellence (PINNACLE) Registry, we sought to characterize overall use, temporal trends in use, and the extent of practice-level variation in the use of any direct oral anticoagulant and warfarin among patients with valvular AF from January 1, 2013, to March 31, 2019.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 23 May 2021; 240:58-62
Hess PL, Gosch KL, Jani SM, Varosy PD, ... Michael Ho P, Virani SS
Am Heart J: 23 May 2021; 240:58-62 | PMID: 34033802
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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: 09 May 2021; epub ahead of print
Chen Y, Lawrence J, Stockbridge N
Am Heart J: 09 May 2021; epub ahead of print | PMID: 33984319
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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: 09 May 2021; 240:1-10
Lee DS, Straus SE, Austin PC, Mohamed S, ... Mak S, Ross HJ
Am Heart J: 09 May 2021; 240:1-10 | PMID: 33984316
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Impact:
Abstract

Individuals aged 1-64 years with documented congenital heart defects at healthcare encounters, five U.S. surveillance sites, 2011-2013.

Jill Glidewell M, Farr SL, Book WM, Botto L, ... Sommerhalter KM, Crume TL
Background
Many individuals born with congenital heart defects (CHD) survive to adulthood. However, population estimates of CHD beyond early childhood are limited in the U.S.
Objectives
To estimate the percentage of individuals aged 1-to-64 years at five U.S. sites with CHD documented at a healthcare encounter during a three-year period and describe their characteristics.
Methods
Sites conducted population-based surveillance of CHD among 1 to 10-year-olds (three sites) and 11 to 64-year-olds (all five sites) by linking healthcare data. Eligible cases resided in the population catchment areas and had one or more healthcare encounters during the surveillance period (January 1, 2011-December 31, 2013) with a CHD-related ICD-9-CM code. Site-specific population census estimates from the same age groups and time period were used to assess percentage of individuals in the catchment area with a CHD-related ICD-9-CM code documented at a healthcare encounter (hereafter referred to as CHD cases). Severe and non-severe CHD were based on an established mutually exclusive anatomic hierarchy.
Results
Among 42,646 CHD cases, 23.7% had severe CHD and 51.5% were male. Percentage of CHD cases among 1 to 10-year-olds, was 6.36/1,000 (range: 4.33-9.96/1,000) but varied by CHD severity [severe: 1.56/1,000 (range: 1.04-2.64/1,000); non-severe: 4.80/1,000 (range: 3.28-7.32/1,000)]. Percentage of cases across all sites in 11 to 64-year-olds was 1.47/1,000 (range: 1.02-2.18/1,000) and varied by CHD severity [severe: 0.34/1,000 (range: 0.26-0.49/1,000); non-severe: 1.13/1,000 (range: 0.76-1.69/1,000)]. Percentage of CHD cases decreased with age until 20 to 44 years and, for non-severe CHD only, increased slightly for ages 45 to 64 years.
Conclusion
CHD cases varied by site, CHD severity, and age. These findings will inform planning for the needs of this growing population.

Published by Elsevier Inc.

Am Heart J: 02 May 2021; 238:100-108
Jill Glidewell M, Farr SL, Book WM, Botto L, ... Sommerhalter KM, Crume TL
Am Heart J: 02 May 2021; 238:100-108 | PMID: 33951414
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Impact:
Abstract

Cardiovascular safety and efficacy of vadadustat for the treatment of anemia in non-dialysis-dependent CKD: Design and baseline characteristics.

Chertow GM, Pergola PE, Agarwal R, Block GA, ... Winkelmayer WC, Eckardt KU
Current clinical practice guidelines for anemia management in non-dialysis-dependent chronic kidney disease (NDD-CKD) recommend the use of erythropoiesis-stimulating agents (ESAs) as standard of care. Vadadustat, an investigational oral hypoxia-inducible factor prolyl-hydroxylase inhibitor, stimulates endogenous erythropoietin production. The PRO2TECT program comprises 2 global, Phase 3, randomized, open-label, active-controlled, sponsor-blind clinical trials to evaluate safety and efficacy of vadadustat vs darbepoetin alfa in adult patients with anemia associated with NDD-CKD. Patients recruited into the ESA-untreated NDD-CKD trial (N = 1751) had hemoglobin <10 g/dL and had not received an ESA within 8 weeks prior to inclusion in the study. Patients recruited into the ESA-treated NDD-CKD trial (N = 1725) had hemoglobin between 8 and 11 g/dL (US) or 9 and 12 g/dL (non-US) and were actively treated with an ESA for anemia associated with CKD. Trial periods in both trials include (1) correction/conversion (weeks 0-23); (2) maintenance (weeks 24-52); (3) long-term treatment (week 53 to end of treatment); and (4) safety follow-up (end-of-treatment to 4 weeks later). The primary safety endpoint is time to first adjudicated major adverse cardiovascular event, defined as all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke, pooled across both trials. The primary efficacy endpoint in each trial is change in hemoglobin from baseline to primary evaluation period (weeks 24-36), comparing vadadustat vs darbepoetin alfa treatment groups. Demographics and baseline characteristics are similar among patients in both trials and broadly representative of the NDD-CKD population. These trials will help to evaluate the safety and efficacy of vadadustat for management of anemia associated with NDD-CKD.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 29 Apr 2021; 235:1-11
Chertow GM, Pergola PE, Agarwal R, Block GA, ... Winkelmayer WC, Eckardt KU
Am Heart J: 29 Apr 2021; 235:1-11 | PMID: 33129989
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Impact:
Abstract

Impact of targeted pulmonary arterial hypertension therapy in patients with combined post- and precapillary pulmonary hypertension.

Moghaddam N, Swiston JR, Tsang MYC, Levy R, Lee L, Brunner NW
Background
Combined post- and precapillary pulmonary hypertension (CpcPH) portends poor outcomes in pulmonary hypertension related to left heart disease (PH-LHD). While recent evidence does not support the use of targeted pulmonary arterial hypertension (PAH) therapy in PH-LHD, there is a lack of clinical data on their use in CpcPH. We evaluated the outcomes in patients with CpcPH treated with PAH therapies.
Methods
Retrospectively, 50 patients meeting hemodynamic criteria of CpcPH and started on PAH-targeted drugs were identified. Fifty age- and gender-matched PAH patients were chosen as controls. We evaluated the change in 6-minute walk distance, World Health Organization functional class (FC), tricuspid annular plane systolic excursion, BNP or NT-proBNP, and pulmonary artery systolic pressure at 3, 6, 12, and 24 months of follow-up.
Results
After adjusting for age and gender, there was no improvement in World Health Organization FC in CpcPH over 2 years (odds ratio of change to FC I/II 1.01, 95% CI: 0.98-1.04). There was no significant improvement in 6-minute walk distance (β coefficient 0.21, 95% CI: -0.98 to 1.4), reduction in BNP/NT-proBNP (β coefficient -12.16, 95% CI: -30.68 to 6.37), increase in tricuspid annular plane systolic excursion (β coefficient 0.074, 95% CI: 0.010-0.139), or decrease in pulmonary artery systolic pressure (0.996, 95% CI: 0.991-1.011) in CpcPH with therapy. There was higher mortality in CpcPH compared to PAH on treatment (24% vs 4%, P = .003).
Conclusions
There were no improvements in symptoms, exercise capacity, or echocardiographic parameters with PAH-targeted therapy in CpcPH. Further studies into potential treatments benefiting this population are needed.

Copyright © 2021. Published by Elsevier Inc.

Am Heart J: 29 Apr 2021; 235:74-81
Moghaddam N, Swiston JR, Tsang MYC, Levy R, Lee L, Brunner NW
Am Heart J: 29 Apr 2021; 235:74-81 | PMID: 33422519
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Impact:
Abstract

Bleeding avoidance strategies and percutaneous coronary intervention outcomes: A 10-year observation from a Japanese Multicenter Registry.

Sawano M, Spertus JA, Masoudi FA, Rumsfeld JS, ... Fukuda K, Kohsaka S
Background
Bleeding avoidance strategies (BASs) are increasingly adopted for patients undergoing percutaneous coronary intervention (PCI) due to bleeding complications. However, their association with bleeding events outside of Western countries remains unclear. In collaboration with the National Cardiovascular Data Registry (NCDR) CathPCI registry, we aimed to assess the time trend and impact of BAS utilization among Japanese patients.
Methods
Our study included 19,656 consecutive PCI patients registered over 10 years. These patients were divided into 4-time frame groups (T1: 2008-2011, T2: 2012-2013, T3: 2014-2015, and T4: 2016-2018). BAS was defined as the use of transradial approach or vascular closure device (VCD) use after transfemoral approach (TFA). Model performance of the NCDR CathPCI bleeding model was evaluated. The degree of bleeding reduction associated with BAS adoption was estimated via multilevel mixed-effects multivariable logistic regression analysis.
Results
The NCDR CathPCI bleeding risk score demonstrated good discrimination in the Japanese population (C-statistics 0.79-0.81). The BAS adoption rate increased from 43% (T1) to 91% (T4), whereas the crude CathPCI-defined bleeding rate decreased from 10% (T1) to 7% (T4). Adjusted odds ratios for bleeding events were 0.25 (95% confidence interval, 0.14-0.45, P< .001) for those undergoing TFA with VCD in T4 and 0.26 (95% confidence interval 0.20-0.35, P< .001) for transradial approach in T4 compared to patients that received TFA without VCD in T1.
Conclusions
BAS use over the studied time frames was associated with lower risk of bleeding complications among Japanese. Nonetheless, observed bleeding rates remained higher compared to the US population.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Apr 2021; 235:113-124
Sawano M, Spertus JA, Masoudi FA, Rumsfeld JS, ... Fukuda K, Kohsaka S
Am Heart J: 29 Apr 2021; 235:113-124 | PMID: 33472053
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Impact:
Abstract

Rationale and design of the CLEAR-outcomes trial: Evaluating the effect of bempedoic acid on cardiovascular events in patients with statin intolerance.

Nicholls S, Lincoff AM, Bays HE, Cho L, ... Wolski K, Nissen SE
Although statins play a pivotal role in the prevention of atherosclerotic cardiovascular disease, many patients fail to achieve recommended lipid levels due to statin-associated muscle symptoms. Bempedoic acid is an oral pro-drug that is activated in the liver and inhibits cholesterol synthesis in hepatocytes, but is not activated in skeletal muscle which has the potential to avoid muscle-related adverse events. Accordingly, this agent effectively lowers atherogenic lipoproteins in patients who experience statin-associated muscle symptoms. However, the effects of bempedoic acid on cardiovascular morbidity and mortality have not been studied. STUDY
Design:
Cholesterol Lowering via Bempedoic acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes is a randomized, double-blind, placebo-controlled clinical trial. Included patients must have all of the following: (i) established atherosclerotic cardiovascular disease or have a high risk of developing atherosclerotic cardiovascular disease, (ii) documented statin intolerance, and (iii) an LDL-C ≥100 mg/dL on maximally-tolerated lipid-lowering therapy. The study randomized 14,014 patients to treatment with bempedoic acid 180 mg daily or matching placebo on a background of guideline-directed medical therapy. The primary outcome is a composite of the time to first cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. The trial will continue until 1620 patients experience a primary endpoint, with a minimum of 810 hard ischemic events (cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) and minimum treatment duration of 36 months and a projected median treatment exposure of 42 months.
Conclusions:
CLEAR Outcomes will determine whether bempedoic acid 180 mg daily reduces the incidence of adverse cardiovascular events in high vascular risk patients with documented statin intolerance and elevated LDL-C levels.


Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 29 Apr 2021; 235:104-112
Nicholls S, Lincoff AM, Bays HE, Cho L, ... Wolski K, Nissen SE
Am Heart J: 29 Apr 2021; 235:104-112 | PMID: 33470195
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Impact:
Abstract

Edoxaban versus warfarin in patients with atrial fibrillation in relation to the risk of stroke: A secondary analysis of the ENGAGE AF-TIMI 48 study.

de Groot JR, Ruff CT, Murphy SA, Hamershock RA, ... Antman EM, Giugliano RP
Introduction
The efficacy and safety of the oral factor Xa inhibitor edoxaban compared to warfarin stratified by CHA2DS2VASc scores have not been described.
Methods
The ENGAGE AF-TIMI 48 trial randomized patients with atrial fibrillation to once-daily edoxaban or warfarin. We classified patients based on CHA2DS2VASc score and compared pharmacokinetics (edoxaban concentration), pharmacodynamics (anti-factor Xa [FXa] with edoxaban, time-in-therapeutic range for warfarin), efficacy (stroke or systemic embolism [SSE]), safety (major bleeding [MB], intracranial hemorrhage), and cardiovascular mortality, for the approved edoxaban regimen vs warfarin.
Results
The distribution CHA2DS2VASc score were:≤3, N = 4159 (29.6%); 4, N = 4066 (28.9%); 5, N = 3165 (22.5%); and ≥6, N = 2681 (19.1%). Increasing rates of SSE (1.05 to 2.99%/year) and MB (2.27 to 4.66%/year) were observed in the warfarin arm as the CHA2DS2VASc score increased. The hazard ratios per unit increase of CHA2DS2VASc score were 1.29 (1.21-1.38) and 1.26 (1.17-1.36) for SSE, and 1.20 (1.13-1.27) and 1.19 (1.12-1.27) for MB, with warfarin and edoxaban, respectively. Time-in-therapeutic range in warfarin-treated patients was similar and high (median 68%-69%) across CHA2DS2VASc scores, whereas edoxaban trough concentration, exogenous anti-FXa activity and %inhibition of endogenous FXa were higher at increasing CHA2DS2VASc scores. Edoxaban reduced SSE, MB, intracranial hemorrhage, and cardiovascular mortality vs warfarin to a similar degree across the range of CHA2DS2VASc scores (P-int = 0.90, 0.96, 0.21, and 0.37, respectively). Because of higher event rates the number of events prevented with edoxaban tended to be greater in patients with higher CHA2DS2VASc scores.
Conclusion
The benefit and safety of edoxaban versus warfarin is maintained across CHA2DS2VASc scores. While the relative risk reductions remain similar, edoxaban provides incrementally larger absolute reductions in outcomes over warfarin in patients with higher CHA2DS2VASc scores.

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

Am Heart J: 29 Apr 2021; 235:132-139
de Groot JR, Ruff CT, Murphy SA, Hamershock RA, ... Antman EM, Giugliano RP
Am Heart J: 29 Apr 2021; 235:132-139 | PMID: 33493453
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Impact:
Abstract

Red blood cell transfusion threshold and mortality in cardiac intensive care unit patients.

Jentzer JC, Lawler PR, Katz JN, Wiley BM, ... Barsness GW, Kor DJ
Background
The benefit of red blood cell (RBC) transfusion in anemic critically-ill patients with cardiovascular disease is uncertain, as is the optimal threshold at which RBC transfusion should be considered. We sought to examine the association between RBC transfusion and mortality stratified by nadir Hgb level and admission diagnosis among cardiac intensive care unit (CICU) patients.
Methods
Retrospective single-center cohort of 11,754 CICU patients admitted between 2007 and 2018. The association between RBC transfusion and hospital mortality at each nadir Hgb (<8 g/dL, 8-9.9 g/dL, ≥10 g/dL) was assessed using multivariable logistic regression adjusted for the propensity to receive RBC transfusion.
Results
The study population had a mean age of 68±15 years, including 38% females; 1,134 (11.4%) received RBC transfusion. Admission diagnoses included: acute coronary syndrome , 42%; heart failure, 50%; cardiac arrest , 12%; and cardiogenic shock , 12%. Patients who received RBC transfusion had higher crude hospital mortality (19% vs. 8%, P<.001). RBC transfusion was associated with lower adjusted hospital mortality in patients with nadir Hgb <8 g/dL after propensity adjustment, including subgroups with acute coronary syndrome, cardiac arrest, or cardiogenic shock (all P <.01). RBC transfusion was not associated with lower adjusted hospital mortality in any subgroup of patients with nadir Hgb ≥8 g/dL.
Conclusions
These observational data suggest the use of a Hgb threshold <8 g/dL for RBC transfusion in most CICU patients, although we could not exclude a potential benefit of RBC transfusion at a nadir Hgb of 8 to 9.9 g/dL; we did not observe any benefit from RBC transfusion at a nadir Hgb ≥10 g/dL.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Apr 2021; 235:24-35
Jentzer JC, Lawler PR, Katz JN, Wiley BM, ... Barsness GW, Kor DJ
Am Heart J: 29 Apr 2021; 235:24-35 | PMID: 33497698
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Impact:
Abstract

Variation in use and dosing escalation of renin angiotensin system, mineralocorticoid receptor antagonist, angiotensin receptor neprilysin inhibitor and beta-blocker therapies in heart failure and reduced ejection fraction: Association of comorbidities.

Albert NM, Tyson RJ, Hill CL, DeVore AD, ... Thomas L, Fonarow GC
Background
In patients with heart failure and reduced ejection fraction (HFrEF), angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), or angiotensin receptor neprilysin inhibitor (ARNI), mineralocorticoid receptor antagonists (MRA), and beta-blockers (βB) are underutilized. It is unknown if patients with and without comorbidities have similar ACEi/ARB/ARNI, MRA, and βB prescription patterns.
Methods
Baseline data from the CHAMP-HF (Change the Management of Patients with Heart Failure) registry were categorized by history of atrial fibrillation, asthma/chronic lung disease, obstructive sleep apnea, and depression. Using multivariate hierarchical logistic models, associations of ACEi/ARB/ARNI, MRA and βB medication use and dose by comorbidities were assessed after adjusting for patient characteristics.
Results
Of 4,815 HFrEF patients from 152 CHAMP-HF sites, ACEi/ARB/ARNI use was lower in patients with more comorbidities, and generally, MRA use was low and βB use was high. In adjusted analyses, patients with HFrEF and comorbid obstructive sleep apnea, vs. without, were more likely to be prescribed ARNI (OR [95% CI]: 1.25 [1.00, 1.55]); P = .047 and MRA (1.31 [1.11, 1.55]); P = .002 and less likely to be prescribed ACEi (0.74 [0.63, 0.88]); P < .001. Patients with atrial fibrillation, vs. without, were less likely to receive ACEi/ARB (0.82 [0.71, 0.95]); P = .006 and any study medication (0.81 [0.67, 0.97]); P = .020. Comorbid lung disease and history of depression were not associated with HFrEF prescriptions.
Conclusions
Renin-angiotensin-aldosterone blockade therapy prescription and dose varied by comorbidity status, but βB therapy did not. In quality efforts, leaders need to consider use and dosing of prescriptions in light of prevalent comorbidities.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Apr 2021; 235:82-96
Albert NM, Tyson RJ, Hill CL, DeVore AD, ... Thomas L, Fonarow GC
Am Heart J: 29 Apr 2021; 235:82-96 | PMID: 33497697
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Impact:
Abstract

Periodontal Disease, Atrial Fibrillation and Stroke.

Sen S, Redd K, Trivedi T, Moss K, ... Beck J, Offenbacher S
Background
We recently described the association between periodontal disease (PD) and stroke risk.
Purpose
The purpose of this study was to test the association between PD, dental care utilization and incident atrial fibrillation (AF), as well as AF as a mediator to PD- stroke association.
Methods
In dental cohort of the Atherosclerosis Risk in Communities Study (ARIC), participants without prior AF underwent full-mouth periodontal measurements. PD was defined on an ordinal scale as healthy (referent), mild, moderate and severe. In ARIC main cohort, participants were classified as regular or episodic dental care users. These patients were followed for AF, over 17 years. Cox proportional hazards models adjusted for AF risk factors were used to study relationships between PD severity, dental care utilization and AF. Mediation analysis was used to test if AF mediated the PD- stroke association.
Results
In dental ARIC cohort, 5,958 were assessed without prior AF, 754 were found to have AF. Severe PD was associated with AF on both univariable (crude HR, 1.54; 95% CI, 1.26-1.87) and multivariable (adjusted HR, 1.31, 95% CI, 1.06-1.62) analyses. Mediation analysis suggested AF mediates the association between PD and stroke. In the main ARIC cohort, 9,666 participants without prior AF were assessed for dental care use, 1558 were found to have AF. Compared with episodic users, regular users had a lower risk for AF on univariable (crude HR, 0.82, 95% CI, 0.74-0.90) and multivariable (adjusted HR, 0.88, 95% CI, 0.78-0.99) analyses.
Conclusions
PD is associated with AF. The association may explain the PD-stroke risk. Regular users had a lower risk of incident AF compared with episodic users.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Apr 2021; 235:36-43
Sen S, Redd K, Trivedi T, Moss K, ... Beck J, Offenbacher S
Am Heart J: 29 Apr 2021; 235:36-43 | PMID: 33503409
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Impact:
Abstract

Impact of insurance status on ICD implantation practice patterns: Insights from the NCDR ICD registry.

Ahmed I, Merchant FM, Curtis JP, Parzynski CS, Lampert R
Background
Whether insurance status influences practice patterns in implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT) defibrillators, when indicated, is not known.
Methods and results
We analyzed the NCDR ICD Registry to evaluate associations of insurance status with guidelines-based receipt of CRT, as well as device-type, complication rates, and use of optimal medical therapy defined by guidelines. Among 798,028 patients with de novo ICD implants, we included only patients < 65 years (those older have Medicare) and excluded those admitted before 2006 (n=1,835) or with insurance coverage other than Medicare, Medicaid or private insurance (n=25,695) leaving 286,556 for analysis. Inverse probability of treatment weighting was used to control for imbalances between groups. Mean age was 53 years, 29% were female. Patients with private insurance and Medicare were more likely to receive CRT-D when indicated (79.6%, OR 1.19 95% CI 1.09-1.28, P <.001 and 78.5%, OR 1.11 95% CI 1.01-1.21 P = .03, respectively) compared to the uninsured (76.7%). The uninsured were also more likely than other groups to receive a single-chamber device. Complication rates did not differ. Uninsured patients were, however, more likely to receive optimal medical therapy, particularly in the subgroup receiving the implant for primary prevention.
Conclusions
In propensity-weighted analysis, uninsured patients are less likely to receive CRT when indicated but more likely to be receiving optimal medical therapy at discharge. Reasons for differences in device implantation practices based on insurance status require further study.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Apr 2021; 235:44-53
Ahmed I, Merchant FM, Curtis JP, Parzynski CS, Lampert R
Am Heart J: 29 Apr 2021; 235:44-53 | PMID: 33503408
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Impact:
Abstract

Prevalence of ideal cardiovascular health in young adults: A birth cohort from southern Brazil.

Oliveira RS, Schneider BC, Callo-Quinte G, Oliveira IO, ... Wehrmeister FC, Menezes AMB
Background
Ideal cardiovascular health (ICH) aims at primordial prevention of cardiovascular diseases in the population. However, there is a lack of research describing ICH in youth from middle-income countries. The aims of this study were to describe the prevalence of ICH at 18- and 22-year-old and to investigate the influence of socioeconomic status.
Methods
The sample consisted of participants from the Pelotas 1993 birth-cohort followed-up at 18- (n = 4,106) and 22-year-old (n = 3,810). Ideal metrics were created for diet, smoking, body mass index, physical activity, blood pressure, total cholesterol, and blood glucose. The presence of 4 or more ideal metrics was defined as ICH. Socioeconomic status was obtained using wealth quintiles calculated with factor analysis based on analysis based on the ownership of household and education. The impact of socioeconomic status on ICH metrics was statistically measured using the slope index of inequality.
Results
The prevalence of ICH was 84.5% (95% confidence interval [CI] = 82.7-86.2%) and 84.1% (82.3-85.8%) at 18-year-old and decreased to 61.1% (58.4-63.7%) and 68.7% (66.2-71.2%) at 22-years old, for male and female, respectively. Socioeconomic status influenced ICH and its components differently in males and females. Wealthiest females had ICH prevalence 19 percentage points (pp) (11-27 pp) higher compared to the poorest, whereas poorest males had ICH prevalence 12 pp (1-21 pp) higher compared to the wealthiest. Longitudinal decreases in ICH components were mostly present in the poorest females.
Conclusions
In middle-income countries, the prevalence of ICH is high at 18-year-old and decreases in a 4-year follow-up. Socioeconomic status influences differently individuals\' ICH between sexes. Efforts are needed to maintain ICH in youth and different strategies may be required between the social status.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Apr 2021; 235:65-73
Oliveira RS, Schneider BC, Callo-Quinte G, Oliveira IO, ... Wehrmeister FC, Menezes AMB
Am Heart J: 29 Apr 2021; 235:65-73 | PMID: 33508220
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Impact:
Abstract

Interventional cardiologists\' perceptions of percutaneous coronary intervention quality measurement and feedback.

Prabhu KM, Don C, Sayre GG, Kearney KE, ... Au DH, Doll JA
Background
Interventional cardiologists receive feedback on their clinical care from a variety of sources including registry-based quality measures, case conferences, and informal peer interactions. However, the impact of this feedback on clinical care is unclear.
Methods
We interviewed interventional cardiologists regarding the use of feedback to improve their care of percutaneous coronary intervention (PCI) patients. Interviews were assessed with template analysis using deductive and inductive techniques.
Results
Among 20 interventional cardiologists from private, academic, and Department of Veterans Affairs practice, 85% were male, 75% performed at least 100 PCIs annually, and 55% were in practice for 5 years or more. All reported receiving feedback on their practice, including formal quality measures and peer learning activities. Many respondents were critical of quality measure reporting, citing lack of trust in outcomes measures and poor applicability to clinical care. Some respondents reported the use of process measures such as contrast volume and fluoroscopy time for benchmarking their performance. Case conferences and informal peer feedback were perceived as timelier and more impactful on clinical care. Respondents identified facilitators of successful feedback interventions including transparent processes, respectful and reciprocal peer relationships, and integration of feedback into collective goals. Hierarchy and competitive environments inhibited useful feedback.
Conclusions
Despite substantial resources dedicated to performance measurement and feedback for PCI, interventional cardiologists perceive existing quality measures to be of only modest value for improving clinical care. Catherization laboratories should seek to integrate quality measures into a holistic quality program that emphasizes peer learning, collective goals and mutual respect.

Published by Elsevier Inc.

Am Heart J: 29 Apr 2021; 235:97-103
Prabhu KM, Don C, Sayre GG, Kearney KE, ... Au DH, Doll JA
Am Heart J: 29 Apr 2021; 235:97-103 | PMID: 33567319
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Impact:
Abstract

Percutaneous coronary intervention in patients with stable coronary artery disease and left ventricular systolic dysfunction: insights from the VA CART program.

Brophy TJ, Warsavage TJ, Hebbe AL, Plomondon ME, ... Gutierrez JA, Swaminathan RV
Background
Revascularization of ischemic cardiomyopathy by coronary artery bypass grafting has been shown to improve survival among patients with left ventricular ejection fraction (LVEF) ≤35%, but the role of percutaneous coronary intervention (PCI) in this context is incompletely described. This study sought to evaluate the effect of PCI on mortality and hospitalization among patients with stable coronary artery disease and reduced left ventricular ejection fraction.
Methods
We performed a retrospective analysis comparing PCI with medical therapy among patients with ischemic cardiomyopathy in the Veterans Affairs Health Administration. Patients with angiographic evidence of 1 or more epicardial stenoses amenable to PCI and LVEF ≤35% were included in the analysis. Outcome data were determined by VA and non-VA data sources on mortality and hospital admission.
Results
From 2008 through 2015, a study sample of 4,628 patients was identified, of which 1,322 patients underwent ad hoc PCI. Patients were followed to a maximum of 3 years. Propensity score weighted landmark analysis was used to evaluate the primary and secondary outcomes. The primary outcome of all-cause mortality was significantly lower in the PCI cohort compared with medical therapy (21.6% vs 30.0%, P <.001). The secondary outcome of all-cause rehospitalization or death was also lower in the PCI cohort (76.5% vs 83.8%, P <.001).
Conclusions
In this retrospective analysis of patients with ischemic cardiomyopathy with coronary artery disease amenable to PCI and LVEF ≤35%, revascularization by PCI was associated with decreased all-cause mortality and decreased all-cause death or rehospitalization.

Published by Elsevier Inc.

Am Heart J: 29 Apr 2021; 235:149-157
Brophy TJ, Warsavage TJ, Hebbe AL, Plomondon ME, ... Gutierrez JA, Swaminathan RV
Am Heart J: 29 Apr 2021; 235:149-157 | PMID: 33567318
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Abstract

Association between ambient air pollution and county-level cardiovascular mortality in the United States by social deprivation index.

Bevan GH, Freedman DA, Lee EK, Rajagopalan S, Al-Kindi SG
Background
Air pollution and socioeconomic status have both been strongly associated with cardiovascular (CV) outcomes. We sought to determine if socioeconomic status modifies the risk association between fine particulate matter air pollution (PM2.5) and CV mortality.
Methods
We linked county-level age-adjusted CV mortality data from Multiple Cause of Death files (2000-2016, ICD10: I00-I99) with 2015 Social Deprivation Index (SDI), a validated estimate of socioeconomic status, and modelled spatial and temporal mean annual PM2.5 exposures (2012-2018). Higher SDI suggests greater deprivation and lower socioeconomic status. Associations between PM2.5 and age adjusted CV mortality were estimated using linear models.
Results
A total of 5,769,315 cardiovascular deaths from 2012-2018 across 3106 United States counties were analyzed. Both PM2.5 (β (SE) 7.584 (0.938), P < .001) and SDI scores (β (SE) 0.591 (0.140), P < .001) were independently associated with age-adjusted CV mortality (R2 = 0.341). The association between PM2.5 and CV mortality were stronger among counties with highest SDI, P value for interaction = .012.
Conclusion
Social deprivation and PM2.5 exposures were independently associated with county level age-adjusted CV mortality. The associations between PM2.5 and CV mortality were stronger in counties with high vs low social deprivation. SDI and PM2.5 represent potential targets to reduce CV mortality disparities and interventions to reduce PM2.5 exposure may be most impactful in communities of low socioeconomic status.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Apr 2021; 235:125-131
Bevan GH, Freedman DA, Lee EK, Rajagopalan S, Al-Kindi SG
Am Heart J: 29 Apr 2021; 235:125-131 | PMID: 33592167
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Abstract

Biodegradable polymer sirolimus-eluting stents vs durable polymer everolimus-eluting stents in patients undergoing percutaneous coronary intervention: A meta-analysis of individual patient data from 5 randomized trials.

Pilgrim T, Rothenbühler M, Siontis GC, Kandzari DE, ... Waksman R, Windecker S
Background
Newest generation drug-eluting stents combine biodegradable polymers with ultrathin stent platforms in order to minimize vessel injury and inflammatory response. Evidence from randomized controlled trials suggested that differences in stent design translate into differences in clinical outcome. The aim of the present study was to evaluate the safety and efficacy of ultrathin strut, biodegradable polymer sirolimus eluting stents (BP SES) compared with thin strut, durable polymer everolimus-eluting stents (DP EES) among patients undergoing percutaneous coronary intervention (PCI).
Methods
We pooled individual participant data from 5 randomized trials (NCT01356888, NCT01939249, NCT02389946, NCT01443104, NCT02579031) including a total of 5,780 patients, and performed a one-stage meta-analysis using a mixed effects Cox regression model.
Results
At a median duration of follow-up of 739 days (interquartile range 365-1,806 days), target-lesion failure occurred in 337 (10.3%) and 304 (12.2%) patients treated with BP SES and DP EES (HR 0.86, 95%CI 0.71-1.06, P = .16). There were no significant differences between BP SES and DP EES with regards to cardiac death (111 (3.4%) vs 102 (4.1%); HR 1.05, 95%CI 0.80-1.37, P = .73), target-vessel myocardial infarction (136 (4.1%) vs 126 (5.0%), HR 0.79, 95%CI 0.62-1.01, P = .061), and clinically-driven target-lesion revascularization (163 (5.0%) vs 147 (5.9%); HR 0.94, 95%CI 0.75-1.18, P = .61). The effect was consistent across major subgroups. In a landmark analysis, there was no significant interaction between treatment effect and timing of events.
Conclusions
In this patient-level meta-analysis of 5 randomized controlled trials, BP SES were associated with a similar risk of target-lesion failure compared with DP EES among patients undergoing PCI.
Study registration
PROSPERO registry (CRD42018109098).

Copyright © 2021 Elsevier Inc. All rights reserved.

Am Heart J: 29 Apr 2021; 235:140-148
Pilgrim T, Rothenbühler M, Siontis GC, Kandzari DE, ... Waksman R, Windecker S
Am Heart J: 29 Apr 2021; 235:140-148 | PMID: 33609498
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This program is still in alpha version.