Journal: Am Heart J

Sorted by: date / impact
Abstract

Effect of permanent right internal mammary artery occlusion on right coronary artery supply: A randomized placebo-controlled clinical trial.

Bigler MR, Stoller M, Tschannen C, Grossenbacher R, Seiler C
Background
Natural, non-surgical internal mammary artery (IMA) bypasses to the coronary circulation have been shown to function as extracardiac sources of myocardial blood supply. The goal of this randomized, placebo-controlled, double blind trial was to test the efficacy of permanent right IMA (RIMA) device occlusion on right coronary artery (RCA) occlusive blood supply, and on clinical and ECG signs of myocardial ischemia.
Methods
This was a prospective superiority trial in 100 patients with chronic coronary artery disease (CAD) randomly allocated (1:1) to RIMA vascular device occlusion (verum group) or to RIMA sham procedure (placebo group). The primary study endpoint was RCA collateral flow index (CFI) as obtained during a 1-minute ostial RCA balloon occlusion at baseline before and at follow-up exam 6weeks after the trial intervention. CFI is the ratio between simultaneous mean coronary occlusive divided by mean aortic pressure both subtracted by central venous pressure. Simultaneously obtained secondary study endpoints were the registration of angina pectoris and quantitative intracoronary (i.c.) ECG ST-segment shift.
Results
CFI change during the follow-up period was +0.036±0.068 in the verum group and-0.021±0.097 in the placebo group (P=.0011). Angina pectoris during the same RCA balloon occlusions had disappeared at follow-up in 14/49 patients of the verum group, and in 4/49 patients of the placebo group (P=.0091). Simultaneous i.c. ECG ST-segment shift change revealed diminished myocardial ischemia at follow-up in the verum group, and more severe ischemia in the placebo group.
Conclusion
Permanent RIMA device occlusion augments right coronary artery supply to the effect of diminishing clinical and electrocardiographic signs of myocardial ischemia during a brief controlled coronary occlusion.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 15 Sep 2020; epub ahead of print
Bigler MR, Stoller M, Tschannen C, Grossenbacher R, Seiler C
Am Heart J: 15 Sep 2020; epub ahead of print | PMID: 32949505
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Abstract

Early rehabilitation in older patients hospitalized with acute decompensated heart failure: A retrospective cohort study.

Takada S, Kondo T, Yasunaga M, Watanabe S, ... Fukuhara S, Yamamoto Y
Background
Although hospitalized patients with acute decompensated heart failure (ADHF) have severe physical dysfunction, little data are available on the comparative effectiveness of early versus late rehabilitation. This study examined the relationship between early compared to late rehabilitation and physical function among older patients hospitalized for ADHF.
Methods
In a retrospective cohort study, independent patients aged ≥65years at baseline who were hospitalized for ADHF from 2012 to 2014 and underwent inpatient rehabilitation were identified using Emergency Department visit data and electronic medical records at two hospitals. Patients were classified into those who underwent early rehabilitation (initiated within 72hours of admission) and late rehabilitation (after 72hours). Primary outcome was length of time from admission until the patient was able to walk independently. Multivariable competing-risk regression with death as the competing event was used to adjust for potential confounding factors, and multiple imputation (MI) analysis was performed.
Results
Of 259 individuals, 30 (11.6%) commenced rehabilitation within 72hours after admission while 229 (88.4%) did so 72hours after admission. Patients who received early rehabilitation had a higher rate of unassisted walking for at least 40m by 30days after admission (hazard ratio: 8.03; 95% confidence interval: 2.15 to 29.98; P=.002 in the multivariable adjusted model) than those who received late rehabilitation. Similar findings were observed on MI analysis.
Conclusion
Early rehabilitation therapy commenced within 72hours of admission was associated with a higher rate of recovery of an activity of daily living (independent walking on a level surface).

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 17 Sep 2020; epub ahead of print
Takada S, Kondo T, Yasunaga M, Watanabe S, ... Fukuhara S, Yamamoto Y
Am Heart J: 17 Sep 2020; epub ahead of print | PMID: 32956621
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Abstract

Levothyroxine dose and risk of atrial fibrillation: a nested case-control study.

Gong IY, Atzema CL, Lega IC, Austin PC, ... Rochon PA, Lipscombe LL
Background
Contemporary data on the effect of levothyroxine dose on the occurrence of atrial fibrillation (AF) are lacking, particularly in the older population. Our objective was to determine the effect of cumulative levothyroxine exposure on risk of AF and ischemic stroke in older adults.
Methods
We conducted a population-based observational study using healthcare databases from Ontario, Canada. We identified adults aged ≥66 years without a history of AF who filled at least one levothyroxine prescription between April 1 2007 and March 31 2016. Cases were defined as cohort members who had incident AF (emergency room visit or hospitalization) between the date of first levothyroxine prescription and December 31, 2017. Index date was date of AF. Cases were matched with up to five controls without AF on the same index date. Secondary outcome was ischemic stroke. Cumulative levothyroxine exposure was estimated based on total milligrams (mg) of levothyroxine dispensed in the year prior to index date. Using nested case-control approach, we compared outcomes between older adults who received high (≥0.125 mg/day), medium (0.075-0.125 mg/day), or low (0-0.075 mg/day) cumulative levothyroxine dose. We compared outcomes between current, recent past, and remote past levothyroxine use.
Results
Of 189,672 older adults treated with levothyroxine (mean age 82 years; 72% women), 30,560 (16.1%) had an episode of AF. Compared to low levothyroxine exposure, high and medium exposure was associated with significantly increased risk of AF after adjustment for covariates (adjusted odds ratio, aOR 1.29, 95% confidence interval, CI 1.23-1.35; aOR 1.08, 95% CI 1.04-1.11; respectively). No association was observed between levothyroxine exposure and ischemic stroke. Compared with current levothyroxine use, older adults with remote levothyroxine use had lower risks of AF (aOR 0.56, 95% CI 0.52-0.59) and ischemic stroke (aOR 0.61, 95% CI 0.56-0.67).
Conclusions
Among older persons treated with levothyroxine, levothyroxine at doses above 0.075 mg/day is associated with an increased risk of AF compared to lower exposure.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 02 Oct 2020; epub ahead of print
Gong IY, Atzema CL, Lega IC, Austin PC, ... Rochon PA, Lipscombe LL
Am Heart J: 02 Oct 2020; epub ahead of print | PMID: 33022231
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Abstract

Cardiac resynchronization therapy improves the ventricular function of patients with Fontan physiology.

Joyce J, O\'Leary ET, Mah DY, Harrild DM, Rhodes J

Past studies have not detected consistent improvement in ventricular function (VFxn) following initiation of cardiac resynchronization therapy (CRT) in Fontan patients. However, these studies employed qualitative assessments of VFxn and/or quantitative assessments of VFxn that rely upon anatomic and/or geometric assumptions that may not be valid in patients with single ventricles. To address this, we used quantitative indices of global VFxn (dP/dt and the Tei index) that are not encumbered by the limitations associated with the indices used in previous studies of CRT in Fontan patients. Methods and results: Patients with Fontan physiology who had received CRT therapy from 2004-2019 were included in the study. They were compared to a concurrent group of Fontan patients who had received standard Dual-Chamber Pacemakers (DCPMs). VFxn was assessed at three time points: prior to, shortly after and late after initiation of pacemaker therapy. Prior to initiation of pacemaker therapy, VFxn of the CRT patients tended to be worse than that of the DCPM patients. For both groups, VFxn appeared to be stable or slightly improved shortly after initiation of pacemaker therapy. In the CRT group, VFxn improved significantly between early and late follow-up. In contrast, VFxn in DCPM patients tended to decline during this period. Changes in VFxn correlated with concurrent changes in New York Heart Association classification. Conclusion: Quantitative assessments of VFxn using indices not confounded by complex cardiac anatomy, segmental wall motions abnormalities or inappropriate geometric assumptions revealed that CRT in Fontan patients is associated with preservation or improvement VFxn compared to standard DCPM. Changes in VFxn correlate with concurrent changes in New York Heart Association classification.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 01 Oct 2020; epub ahead of print
Joyce J, O'Leary ET, Mah DY, Harrild DM, Rhodes J
Am Heart J: 01 Oct 2020; epub ahead of print | PMID: 33017579
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Abstract

Predictors of Fabry disease in patients with hypertrophic cardiomyopathy: How to guide the diagnostic strategy?

Azevedo O, Marques N, Reis L, Cruz I, ... Cunha D,
Background
Fabry disease (FD) is a treatable cause of hypertrophic cardiomyopathy (HCM). We aimed to determine the independent predictors of FD and to define a clinically useful strategy to discriminate FD among HCM.
Methods
Multicenter study including 780 patients with the ESC definition of HCM. FD screening was performed by enzymatic assay in males and genetic testing in females. Multivariate regression analysis identified independent predictors of FD in HCM. A discriminant function analysis defined a score based on the weighted combination of these predictors.
Results
FD was found in 37 of 780 patients with HCM (4.7%): 31 with p.F113L mutation due to a founder effect; and 6 with other variants (p.C94S; p.M96V; p.G183V; p.E203X; p.M290I; p.R356Q/p.G360R). FD prevalence in HCM adjusted for the founder effect was 0.9%. Symmetric HCM (OR 3.464, CI95% 1.151-10.430), basal inferolateral late gadolinium enhancement (LGE) (OR 10.677, CI95% 3.633-31.380), bifascicular block (OR 10.909, CI95% 2.377-50.059) and ST-segment depression (OR 4.401, CI95% 1.431-13.533) were independent predictors of FD in HCM. The score ID FABRY-HCM [-0.729 + (2.781xBifascicular block) + (0.590xST depression) + (0.831xSymmetric HCM) + (2.130xbasal inferolateral LGE)] had a negative predictive value of 95.8% for FD, with a cut-off of 1.0, meaning that, in the absence of both bifascicular block and basal inferolateral LGE, FD is a less probable cause of HCM, being more appropriate to perform HCM gene panel than targeted FD screening.
Conclusion
FD prevalence in HCM was 0.9%. Bifascicular block and basal inferolateral LGE were the most powerful predictors of FD in HCM. In their absence, HCM gene panel is the most appropriate step in etiological study of HCM.

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Am Heart J: 30 Jul 2020; 226:114-126
Azevedo O, Marques N, Reis L, Cruz I, ... Cunha D,
Am Heart J: 30 Jul 2020; 226:114-126 | PMID: 32531501
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Abstract

PROVIDE-HF primary results: Patient-reported outcomes inVestigation following initiation of drug therapy with Entresto (Sacubitril/valsartan) in heart failure.

Mentz RJ, Xu H, O\'Brien EC, Thomas L, ... Duffy CI, Hernandez AF
Background
In PARADIGM-HF, sacubitril/valsartan improved quality of life (QOL) vs. enalapril in heart failure with reduced ejection fraction (HFrEF), yet limited data are available regarding QOL changes after sacubitril/valsartan initiation in routine practice.
Methods
PROVIDE-HF was a prospective study within a national research network (PCORnet) of HFrEF outpatients recently initiated on sacubitril/valsartan vs. controls with recent ACE-I/ARB initiation/dose change. The primary endpoint was mean Kansas City Cardiomyopathy Questionnaire (KCCQ) change through 12weeks. Other endpoints included responder analyses: ≥5-point and≥20-point KCCQ increase. Adjusted QOL change was estimated after propensity score weighting.
Results
Overall, 270 patients had both baseline and 12-week KCCQ data (151 sacubitril/valsartan; 119 control). The groups had similar demographics and HF details: median EF 28% and NT-proBNP 1083pg/mL. Sacubitril/valsartan patients had larger improvements in KCCQ (mean difference+4.76; P=.027) and were more likely to have a≥5-point and≥20-point response (all P<.05). Adjusted comparisons demonstrated similar numerical improvements in the change in KCCQ (+4.55; 95% CI: -0.89, 9.99; P=.101) and likelihood of ≥5-point increase (OR 1.55; 95% CI: 0.84, 2.86; P=.16); ≥20-pt increase remained statistically significant (OR 3.79; 95% CI: 1.47, 9.73; P=.006).
Conclusions
In this prospective HFrEF study of sacubitril/valsartan initiation compared with recent ACE-I/ARB initiation/dose change, the between-group difference in the primary endpoint, mean KCCQ change at 12weeks, was not statistically significant following adjustment, but sacubitril/valsartan initiation was associated with early improvements in QOL and a higher likelihood of ≥20-pt improvement in KCCQ at 12weeks. These data add additional real-world evidence related to patient-reported outcomes following the initiation of sacubitril/valsartan in routine clinical practice.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 23 Sep 2020; epub ahead of print
Mentz RJ, Xu H, O'Brien EC, Thomas L, ... Duffy CI, Hernandez AF
Am Heart J: 23 Sep 2020; epub ahead of print | PMID: 32980364
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Abstract

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial.

Guimarães HP, de Barros E Silva PGM, Liporace IL, Sampaio RO, ... Berwanger O,
Background
The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain.
Design
RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20mg once daily (15mg in those with creatinine clearance <50mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism.
Summary
RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 08 Oct 2020; epub ahead of print
Guimarães HP, de Barros E Silva PGM, Liporace IL, Sampaio RO, ... Berwanger O,
Am Heart J: 08 Oct 2020; epub ahead of print | PMID: 33045224
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Abstract

The DANish randomized, double-blind, placebo controlled trial in patients with chronic HEART failure (DANHEART): A 2 x 2 factorial trial of hydralazine-isosorbide dinitrate in patients with chronic heart failure (H-HeFT) and metformin in patients with chronic heart failure and diabetes or prediabetes (met-HeFT).

Wiggers H, Køber L, Gislason G, Schou M, ... Mellemkjær S, Gustafsson F
Objectives
The DANHEART trial is a multicenter, randomized (1:1), parallel-group, double-blind, placebo-controlled study in chronic heart failure patients with reduced ejection fraction (HFrEF). This investigator driven study will include 1500 HFrEF patients and test in a 2 x 2 factorial design: 1) if hydralazine-isosorbide dinitrate reduces the incidence of death and hospitalization with worsening heart failure vs. placebo (H-HeFT) and 2) if metformin reduces the incidence of death, worsening heart failure, acute myocardial infarction, and stroke vs. placebo in patients with diabetes or prediabetes (Met-HeFT).
Methods
Symptomatic, optimally treated HFrEF patients with LVEF ≤40% are randomized to active vs. placebo treatment. Patients can be randomized in either both H-HeFT and Met-HeFT or to only one of these study arms. In this event-driven study, it is anticipated that 1300 patients should be included in H-HeFT and 1100 in Met-HeFT and followed for an average of 4years.
Results
As of May 2020, 296 patients have been randomized at 20 centers in Denmark.
Conclusion
The H-HeFT and Met-HeFT studies will yield new knowledge about the potential benefit and safety of two commonly prescribed drugs with limited randomized data in patients with HFrEF.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 07 Oct 2020; epub ahead of print
Wiggers H, Køber L, Gislason G, Schou M, ... Mellemkjær S, Gustafsson F
Am Heart J: 07 Oct 2020; epub ahead of print | PMID: 33039340
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Abstract

In-hospital outcomes after bariatric surgery in patients with heart failure.

Blumer V, Greene SJ, Ortiz M, Kittipibul V, ... Mentz RJ, Vest AR

Based on the largest publicly available all-payer inpatient database in the United States, this study sought to evaluate real-world outcomes after bariatric surgery among patients with heart failure.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 25 Sep 2020; epub ahead of print
Blumer V, Greene SJ, Ortiz M, Kittipibul V, ... Mentz RJ, Vest AR
Am Heart J: 25 Sep 2020; epub ahead of print | PMID: 32991845
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Abstract

Menopausal age and left ventricular remodeling by cardiac magnetic resonance imaging among 14,550 women.

Honigberg MC, Pirruccello JP, Aragam K, Sarma AA, ... Wood MJ, Natarajan P

The present study included 14,550 postmenopausal female participants in the UK Biobank who completed cardiac magnetic resonance imaging. Earlier age at menopause was significantly and independently associated with smaller left ventricular end-diastolic volume and smaller stroke volume, a pattern suggesting acceleration of previously described age-related left ventricular remodeling. These findings may have implications for understanding mechanisms of heart failure, specifically heart failure with preserved ejection fraction, among women with early menopause.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 19 Aug 2020; 229:138-143
Honigberg MC, Pirruccello JP, Aragam K, Sarma AA, ... Wood MJ, Natarajan P
Am Heart J: 19 Aug 2020; 229:138-143 | PMID: 32827459
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Abstract

Interobserver agreement of the anatomic and physiological classification system for adult congenital heart disease.

Lachtrupp CL, Valente AM, Gurvitz M, Landzberg MJ, Brainard SB, Opotowsky AR

The Anatomic and Physiological (AP) classification system proposed in the 2018 American College of Cardiology/American Heart Association adult congenital heart disease (ACHD) guidelines assigns 2 dimensions to each patient: anatomic class (AnatC) and physiological stage (PhyS). This approach has not been tested in practice; we assessed interrater reliability and identified sources of disagreement.
Methods
Consensus definitions for AP categories were developed with input from 4 experts. Research assistants (RAs) assigned AnatC/PhyS for patients in the Boston ACHD Biobank, a prospectively enrolled cohort of ambulatory ACHD patients ≥18 years old seen between 2012 and 2019. Two (of 4) expert reviewers then independently assigned AnatC/PhyS for 41 patients. Interrater reliability was assessed with linearly weighted kappa (κ) for agreement between (1) experts and (2) an RA and an expert. Experts examined disagreements and identified sources of variability and areas requiring clarification.
Results
Interexpert agreement for AnatC was excellent, with agreement on 38/41 (92.7%) cases and κ 0.88 [0.75, 1.01]. Agreement for PhyS was less robust, with consensus on 24/41 cases (59.5%), κ 0.57 [0.39, 0.75]. Expert-RA agreement was lower for AnatC (κ 0.77 [0.60, 0.95]), whereas PhyS was similar to interexpert agreement (κ 0.53 [0.34, 0.72]). There was ambiguity in the definitions of (1) arrhythmia status, (2) cyanotic CHD, and (3) valve disease.
Conclusions
Although AnatC can be assessed reliably, that is not true for the PhyS part of the AP classification proposed in the 2018 American College of Cardiology/American Heart Association guidelines. Reliability of PhyS would be strengthened by more precise definitions readily interpretable in clinical practice.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 26 Jul 2020; 229:92-99
Lachtrupp CL, Valente AM, Gurvitz M, Landzberg MJ, Brainard SB, Opotowsky AR
Am Heart J: 26 Jul 2020; 229:92-99 | PMID: 32947058
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Abstract

Internet search volume for chest pain during the COVID-19 pandemic.

Ciofani JL, Han D, Allahwala UK, Asrress KN, Bhindi R

During the COVID-19 pandemic there has been a reduction in hospital admissions for acute myocardial infarction. This manuscript presents the analysis of Google Trends meta-data and shows a marked spike in search volume for chest pain that is strongly correlated with COVID-19 case numbers in the United States. This raises a concern that fear of contracting COVID-19 may be leading patients to self-triage using internet searches. Research Letter. During the COVID-19 pandemic, physicians worldwide have noted reductions in hospital admissions for emergencies including acute myocardial infarction and ischemic stroke. Several explanations have been proposed including reduced air pollution, changes in diet and lifestyle, or, most worryingly, avoidance of hospitals to reduce the risk of COVID-19 infection. There is significant concern that instead of presenting to hospital, fear of COVID-19 has led patients to self-triage using internet searches. Google Trends™ is a free publicly available tool that monitors how often search items are queried over time and provides insights into public health behavior. Recommendations for the documentation of Google Trends™ analyses have previously been published and were consulted to facilitate reproducibility of the present study. We quantified searches in the United States (US) for the symptom of interest, chest pain, and the control terms toothache, abdominal pain, knee pain, heart attack and stroke (time period 1st Jan 2017 to 24th May 2020, accessed 28th May 2020, no quotation marks, no combination symbols, all query categories). Data on the number of COVID-19 cases per day in the US was retrieved from USAFacts.org, which collates data from government agencies and is used by the Centers for Disease Control and Prevention. Time-lag correlation analysis was performed using R. To assess the relationship between chest pain searches and COVID-19 caseload, data on search volume was also collected for the states with the highest and lowest numbers of COVID-19 cases. No extramural funding was used to support this work. The number of cases of COVID-19 in the US rose rapidly throughout March 2020 and during the same month the relative search frequency of the symptom chest pain, but not the control terms, nearly doubled compared to the previous three years (Figure 1A). There was a strong correlation between the number of new COVID-19 cases and Google search queries for chest pain (Pearson correlation coefficient 0.79 with 18-day time-lag) (Figure 1B). The search volume for chest pain also spiked in the states with the three highest (New York, New Jersey, Illinois), but not the three lowest (Hawaii, Montana, Alaska), COVID-19 caseloads (Figure 2). In this analysis we describe a strong correlation between the increase in COVID-19 cases and the utilization of Google for medical information. Chest pain is a common presenting symptom of life-threatening medical conditions including coronary artery disease, aortic dissection and pulmonary embolus, but is not a common symptom of COVID-19. The analysis presented here suggests that the rise in COVID-19 cases has led patients to seek medical information about their symptoms from the internet at substantially higher rates compared to the previous three years. This does not appear to be due to generally increased search volumes nor seasonal variation (Figure 1). Within the US this was observed in states with a high prevalence of COVID-19 but not states with a low prevalence (Figure 2). This was despite all analyzed states instituting stay-at-home orders, which suggests this phenomenon is not related to lockdown restrictions. This raises a significant concern that in regions where caseloads are high, fear of contracting COVID-19 may be leading patients to self-triage, potentially in lieu of presenting to hospital. The rise in search volume for \'chest pain\' but not \'heart attack\' or \'stroke\' may be explained by several hypotheses, including patients being more likely to search for symptoms rather than diagnoses, or it may reflect the reduced hospitalisations for these conditions during the COVID-19 pandemic and hence fewer patients receiving the diagnostic labels \'heart attack\' and \'stroke\'. Indeed it was recently reported that the rate of catheter laboratory activation for ST-segment elevation myocardial infarction has decreased by 38% in the US compared to the pre-COVID-19 period, and there have been similar reductions in hospital presentations for other life-threatening conditions such as acute aortic dissection. This has been accompanied by a concurrent increase in out-of-hospital cardiac arrests and, amongst patients that did present to hospital with acute myocardial infarction, increased rates of delayed presentation and complications. While COVID-19 has a mortality of approximately 1%, acute myocardial infarction in the absence of contemporary treatment has a one-month mortality of up to 50%. As lockdown regulations begin to relax worldwide there is a significant risk of a second-wave of COVID-19, and so it is critical to re-emphasize to patients that internet searches are not an alternative to professional medical attention.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 29 Sep 2020; epub ahead of print
Ciofani JL, Han D, Allahwala UK, Asrress KN, Bhindi R
Am Heart J: 29 Sep 2020; epub ahead of print | PMID: 33010246
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Abstract

Trends in first-time hospitalization, management, and short-term mortality in acute myocardial infarction-related cardiogenic shock from 2005 to 2017: A nationwide cohort study.

Lauridsen MD, Rørth R, Lindholm MG, Kjaergaard J, ... Køber L, Fosbøl EL
Background
Cardiogenic shock remains the leading cause of in-hospital death in acute myocardial infarction (AMI). Because of temporary changes in management of cardiogenic shock with widespread implementation of early revascularization along with increasing attention to the use of mechanical circulatory devices, complete and longitudinal data are important in this subject. The objective of this study was to examine temporal trends of first-time hospitalization, management, and short-term mortality for patients with AMI-related cardiogenic shock (AMICS).
Methods
Using nationwide medical registries, we identified patients hospitalized with first-time AMI and cardiogenic shock from January 1, 2005, through December 31, 2017. We calculated annual incidence proportions of AMICS. Thirty-day mortality was estimated with use of Kaplan-Meier estimator comparing AMICS and AMI-only patients. Multivariable Cox regression models were used to assess mortality rate ratios.
Results
We included 101,834 AMI patients of whom 7,040 (7%) had AMICS. The median age was 72 (interquartile range: 62-80) for AMICS and 69 (interquartile range: 58-79) for AMI-only patients. The gender composition was similar between AMICS and AMI-only patients (male: 64% vs 63%). The annual incidence proportion of AMICS decreased slightly over time (2005: 7.0% vs 2017: 6.1%, P for trend < .0001). In AMICS, use of coronary angiography increased between 2005 and 2017 from 48% to 71%, as did use of left ventricular assist device (1% vs 10%) and norepinephrine (30% to 70%). In contrast, use of intra-aortic balloon pump (14% vs 1%) and dopamine (34% vs 20%) decreased. Thirty-day mortality for AMICS patients was 60% (95% CI: 59-61) and substantially higher than the 8% (95% CI: 7.8-8.2) for AMI-only patients (mortality rate ratio: 11.4, 95% CI: 10.9-11.8). Over time, the mortality decreased after AMICS (2005: 68% to 2017: 57%, P for temporal change in adjusted analysis < .0001).
Conclusions
We observed a slight decrease in AMICS hospitalization over time with changing practice patterns. Thirty-day mortality was markedly higher for patients with AMICS compared with AMI only, yet our results suggest improved 30-day survival over time after AMICS.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 27 Aug 2020; 229:127-137
Lauridsen MD, Rørth R, Lindholm MG, Kjaergaard J, ... Køber L, Fosbøl EL
Am Heart J: 27 Aug 2020; 229:127-137 | PMID: 32861678
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Abstract

Physiology-guided revascularization versus optimal medical therapy of nonculprit lesions in elderly patients with myocardial infarction: Rationale and design of the FIRE trial.

Biscaglia S, Guiducci V, Santarelli A, Amat Santos I, ... Colombo A, Campo G
Background
Myocardial infarction (MI) in elderly patients is associated with unfavorable prognosis, and it is becoming an increasingly prevalent condition. The prognosis of elderly patients is equally impaired in ST-segment elevation (STE) or non-STE (NSTE), and it is markedly worsened by the common presence of multivessel disease (MVD). Given the limited evidence available for elderly patients, it has not yet been established whether, as for younger patients, a complete revascularization strategy in MI patients with MVD should be advocated. We present the design of a dedicated study that will address this research gap.
Methods and design
The FIRE trial is a prospective, randomized, international, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients aged 75 years and older, with MI (either STE or NSTE), MVD at coronary artery angiography, and a clear culprit lesion will be randomized to culprit-only treatment or to physiology-guided complete revascularization. The primary end point will be the patient-oriented composite end point of all-cause death, any MI, any stroke, and any revascularization at 1 year. The key secondary end point will be the composite of cardiovascular death and MI. Quality of life and physical performance will be evaluated as well. All components of the primary and key secondary outcome will be tested also at 3 and 5 years. The sample size for the study is 1,400 patients.
Implications
The FIRE trial will provide evidence on whether a specific revascularization strategy should be applied to elderly patients presenting MI and MVD to improve their clinical outcomes.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 17 Aug 2020; 229:100-109
Biscaglia S, Guiducci V, Santarelli A, Amat Santos I, ... Colombo A, Campo G
Am Heart J: 17 Aug 2020; 229:100-109 | PMID: 32822656
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Abstract

Cost-effectiveness of combined catheter ablation and left atrial appendage closure for symptomatic atrial fibrillation in patients with high stroke and bleeding risk.

Kawakami H, Nolan MT, Phillips K, Scuffham PA, Marwick TH
Aims
Combined catheter ablation (CA) and left atrial appendage closure (LAAC) has been proposed for management of symptomatic atrial fibrillation (AF) in patients with high stroke and bleeding risk. We assessed the cost-effectiveness of combined CA and LAAC, compared with CA and standard oral anticoagulation (OAC) in symptomatic AF.
Methods
A Markov model was developed to assess total costs, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER) among two post-CA strategies: (1) standard OAC, (2) LAAC (combined CA and LAAC procedure). The base-case used a 10-year time horizon and consisted of a hypothetical cohort of patients aged 65years with symptomatic AF, high thrombotic (CHADS-VASc=3) and bleeding risk (HAS-BLED=3), and planned for AF ablation. Values for transition probabilities, utilities, and costs were derived from the literature. Costs were converted to 2020 USD. Half-cycle correction was applied, and costs and QALYs were discounted at 3% annually. Sensitivity analyses were performed for significant variables and scenario analyses for higher embolic risk.
Results
In the base case cohort of 10,000 patients followed for 10years, total costs for the LAAC strategy were $29,027 and for OAC strategy were $27,896. The LAAC strategy was associated with 122 fewer disabling strokes and 203 fewer ICH per 10,000 patients compared with the OAC strategy. The LAAC strategy had an ICER of $11,072 USD/QALY. In sensitivity analyses, although cost-effectiveness was highly dependent on the risk of intracranial hemorrhage in the LAAC strategy and the cost of the combined procedure, LAAC was superior to OAC under the most circumstances. Scenario analyses demonstrated that the combined procedure was more cost-effective in patients with higher stroke risk.
Conclusion
In symptomatic AF patients with high stroke and bleeding risk who are planned for CA, the combined CA and LAAC procedure may be a cost-effective therapeutic option, and be more beneficial to patients with CHADS-VASc risk score≥3.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 17 Aug 2020; epub ahead of print
Kawakami H, Nolan MT, Phillips K, Scuffham PA, Marwick TH
Am Heart J: 17 Aug 2020; epub ahead of print | PMID: 32822655
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Impact:
Abstract

Implementation of Multifaceted Patient-Centered Treatment Strategies for Intensive Blood Pressure Control (IMPACTS): Rationale and design of a cluster-randomized trial.

Mills KT, Peacock E, Chen J, Zimmerman A, ... Krousel-Wood M, He J
Background
The Systolic Blood Pressure Intervention Trial (SPRINT) reported that intensive blood pressure (BP) treatment reduced cardiovascular disease and mortality compared to standard BP treatment in hypertension patients. The next important question is how to implement more intensive BP treatment in real-world clinical practice. We designed an effectiveness-implementation hybrid trial to simultaneously test the effectiveness of a multifaceted intervention for intensive BP treatment and its feasibility, fidelity, and sustainability in underserved hypertension patients.
Methods
Implementation of Multifaceted Patient-Centered Treatment Strategies for Intensive Blood Pressure Control (IMPACTS) is a cluster randomized trial conducted in 36 Federally Qualified Health Center clinics in Louisiana and Mississippi. Federally Qualified Health Center clinics were randomized to either a multifaceted intervention for intensive BP treatment, including protocol-based treatment using the SPRINT intensive BP management algorithm, dissemination of SPRINT findings, BP audit and feedback, home BP monitoring, and health coaching, or enhanced usual care. Difference in mean systolic BP change from baseline to 18 months is the primary clinical effectiveness outcome, and intervention fidelity, measured by treatment intensification and medication adherence, is the primary implementation outcome. The planned sample size of 1,260 participants (36 clinics with 35 participants each) has 90% power to detect a 5.0-mm Hg difference in systolic BP at a .05 significance level and 80% follow-up rate.
Conclusions
IMPACTS will generate critical data on the effectiveness and implementation of a multifaceted intervention for intensive BP treatment in real-world clinical practice and could directly impact the BP-related disease burden in minority and low-income populations in the United States.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 18 Aug 2020; 230:13-24
Mills KT, Peacock E, Chen J, Zimmerman A, ... Krousel-Wood M, He J
Am Heart J: 18 Aug 2020; 230:13-24 | PMID: 32827458
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Impact:
Abstract

An Electronically delivered, Patient-activation tool for Intensification of medications for Chronic Heart Failure with reduced ejection fraction: Rationale and design of the EPIC-HF trial.

Venechuk GE, Khazanie P, Page RL, Knoepke CE, ... Matlock DD, Allen LA
Background
Heart failure with reduced ejection fraction (HFrEF) benefits from initiation and intensification of multiple pharmacotherapies. Unfortunately, there are major gaps in the routine use of these drugs. Without novel approaches to improve prescribing, the cumulative benefits of HFrEF treatment will be largely unrealized. Direct-to-consumer marketing and shared decision making reflect a culture where patients are increasingly involved in treatment choices, creating opportunities for prescribing interventions that engage patients.
Hypothesis
Encouraging patients to engage providers in HFrEF prescribing decisions will improve the use of guideline-directed medical therapies.
Design
The Electronically delivered, Patient-activation tool for Intensification of Chronic medications for Heart Failure with reduced ejection fraction (EPIC-HF) trial randomizes patients with HFrEF to usual care versus patient-activation tools-a 3-minute video and 1-page checklist-delivered prior to cardiology clinic visits that encourage patients to work collaboratively with their clinicians to intensify HFrEF prescribing. The study assesses the effectiveness of the EPIC-HF intervention to improve guideline-directed medical therapy in the month after its delivery while using an implementation design to also understand the reach, adoption, implementation, and maintenance of this approach within the context of real-world care delivery. Study enrollment was completed in January 2020, with a total 305 patients. Baseline data revealed significant opportunities, with <1% of patients on optimal HFrEF medical therapy.
Summary
The EPIC-HF trial assesses the implementation, effectiveness, and safety of patient engagement in HFrEF prescribing decisions. If successful, the tool can be easily disseminated and may inform similar interventions for other chronic conditions.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 27 Aug 2020; 229:144-155
Venechuk GE, Khazanie P, Page RL, Knoepke CE, ... Matlock DD, Allen LA
Am Heart J: 27 Aug 2020; 229:144-155 | PMID: 32866454
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Impact:
Abstract

Prognostic value of myocardial fibrosis on cardiac magnetic resonance imaging in patients with ischemic cardiomyopathy: A systematic review.

Chery G, Kamp N, Kosinski AS, Schmidler GS, ... Patel M, Al-Khatib SM

The use of cardiac magnetic resonance imaging (c-MRI) in risk stratification for clinical outcomes of patients with ischemic cardiomyopathy (ICM) remains low. This systematic review investigated the prognostic value of myocardial fibrosis as assessed by late gadolinium enhancement (LGE) on c-MRI in patients with ICM for ventricular tachyarrhythmia, sudden cardiac death (SCD), or all-cause mortality.
Methods
We conducted a systematic review of the electronic databases Pubmed and Embase for relevant prospective English-language studies published between January 1990 and February 2019. All included articles were prospective studies that comprised of human participants older than 18 years with ICM and a primary or secondary prevention implantable cardioverter/defibrillator (ICD); had a sample size >30 participants; had at least 6 months of follow-up; and reported on ventricular tachyarrhythmia, SCD, and all-cause mortality. A total of 90 articles related to ICM were identified and were subsequently screened independently by 2 authors. Pooled sensitivity and specificity of LGE were calculated using random-effects model.
Results
Eight studies with 1,085 participants were included in the final analysis. The mean age of patients varied from 43 to 83 years, with most patients being men. The most common comorbidities reported included history of diabetes mellitus (22%-62%), hyperlipidemia (40%-86%), and hypertension (35%-88%). The ejection fraction of each study was reported as mean or median and varied from 22% to 35%. During a follow-up that ranged from 8.5 to 65 months, there were 110 ventricular arrhythmic events reported. The pooled sensitivity and specificity of LGE for ICD therapy delivered for ventricular arrhythmias were 0.79 (95% CI: 0.66-0.87) and 0.28 (95% CI: 0.14-0.46), respectively. For all-cause mortality, the pooled sensitivity and specificity of LGE were 0.76 (95% CI: 0.40-0.93) and 0.41 (95% CI: 0.14-0.75), respectively. Although SCD was of significant interest to our review, only 1 of the studies reported on the association between LGE and SCD, leading to the subsequent exclusion of SCD from the end point analysis.
Conclusions
LGE has high prognostic value in predicting adverse outcomes in patients with ICM and may provide helpful information for clinical decision making related to SCD prevention. Our findings illustrate how LGE may improve current risk stratification, prognostication, and selection of patients with ICM for ICD therapy.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 10 Aug 2020; 229:52-60
Chery G, Kamp N, Kosinski AS, Schmidler GS, ... Patel M, Al-Khatib SM
Am Heart J: 10 Aug 2020; 229:52-60 | PMID: 32916608
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Impact:
Abstract

Timing of randomization after an acute coronary syndrome in patients with type 2 diabetes mellitus.

Elharram M, Sharma A, White W, Bakris G, ... Ferreira JP, Zannad F
Background
The timing of enrolment following an acute coronary syndrome (ACS) may influence cardiovascular (CV) outcomes and potentially treatment effect in clinical trials. Understanding the timing and type of clinical events after an ACS will allow for clinicians to better tailor evidence-based treatments to optimize therapeutic effect. Using a large contemporary trial in patients with type 2 diabetes mellitus (T2DM) post-ACS, we examined the impact of timing of enrolment on subsequent CV outcomes.
Methods
EXAMINE was a randomized trial of alogliptin versus placebo in 5,380 patients with T2DM and a recent ACS from October 2009 to March 2013. The primary outcome was a composite of CV death, nonfatal myocardial infarction (MI), or nonfatal stroke. The median follow-up was 18 months. In this post hoc analysis, we examined the occurrence of subsequent CV events by timing of enrollment divided by tertiles of time from ACS to randomization: 8-34, 35-56, and 57-141 days.
Results
Patients randomized early (compared to the latest times) had less comorbidities at baseline including a history of heart failure (HF; 24.7% vs 33.0%), prior coronary artery bypass graft (9.6% vs 15.9%), or atrial fibrillation (5.9% vs 9.4%). Despite the reduced comorbidity burden, the risk of the primary outcome was highest in patients randomized early compared to the latest time (adjusted hazard ratio 1.47; 95% CI 1.21-1.74). Similarly, patients randomized early had an increased risk of recurrent MI (adjusted hazard ratio 1.51; 95% CI 1.17-1.96) and HF hospitalization (1.49; 95% CI 1.05-2.10).
Conclusions
In a contemporary cohort of T2DM with a recent ACS, the risk for recurrent CV events including MI and HF hospitalization is elevated early after an ACS. Given the emergence of antihyperglycemic therapies that reduce the risk of MI and HF among patients with T2DM at high CV risk, future studies evaluating the initiation of these therapies in the early period following an ACS are warranted given the large burden of potentially modifiable CV events.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 05 Aug 2020; 229:40-51
Elharram M, Sharma A, White W, Bakris G, ... Ferreira JP, Zannad F
Am Heart J: 05 Aug 2020; 229:40-51 | PMID: 32916607
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Impact:
Abstract

Non-vitamin K antagonist oral anticoagulants in very elderly east Asians with atrial fibrillation: A nationwide population-based study.

Kwon S, Lee SR, Choi EK, Choe WS, ... Oh S, Lip GYH
Background
The evidence of effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) among elderly East Asians is limited.
Objectives
We aimed to describe the effectiveness and safety outcomes associated with NOACs and warfarin among elderly Koreans aged ≥80 years.
Methods
Using the Korean Health Insurance Review and Assessment service database, patients with atrial fibrillation (AF) who were naïve to index oral anticoagulant between 2015 and 2017 were included in this study (20,573 for NOACs and 4086 for warfarin). Two treatment groups were balanced using the inverse probability of treatment weighting (IPTW) method. The clinical outcomes including ischemic stroke, major bleeding including intracranial hemorrhage (ICH) and gastrointestinal bleeding (GIB), and a composite of these outcomes were evaluated.
Results
Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio 0.74 [95% confidence interval 0.62-0.89]), and composite outcome (0.78 [0.69-0.90]). NOACs showed nonsignificant trends towards to lower risks of GIB and major bleeding than warfarin. The risk of ICH of NOAC group was comparable with the warfarin group. Among NOACs, apixaban and edoxaban showed better composite outcomes than warfarin. Among the clinical outcomes, only ischemic stroke and the composite outcome had a significant interaction with age subgroups (80-89 years and ≥90 years, P-for-interaction = .097 and .040, respectively).
Conclusion
NOACs were associated with lower risks of ischemic stroke and the composite outcome (ischemic stroke and major bleeding) compared to warfarin in elderly East Asians. Physicians should be more confident in prescribing NOACs to elderly East Asians with AF.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 14 Aug 2020; 229:81-91
Kwon S, Lee SR, Choi EK, Choe WS, ... Oh S, Lip GYH
Am Heart J: 14 Aug 2020; 229:81-91 | PMID: 32927313
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Impact:
Abstract

Contribution of individual components to composite endpoints in contemporary cardiovascular randomized controlled trials.

Shaikh A, Ochani RK, Khan MS, Riaz H, ... Kalra A, Krasuski RA
Objective
Cardiovascular randomized controlled trials (RCTs) typically set composite endpoints as the primary outcome to enhance statistical power. However, influence of individual component endpoints on overall composite outcomes remains understudied.
Methods
We searched MEDLINE for RCTs published in 6 high impact journals (the Lancet, the New England Journal of Medicine, Journal of the American Medical Association, Circulation, Journal of the American College of Cardiology and the European Heart Journal) from 2011 to 2017. 2-armed, parallel-design cardiovascular RCTs which reported composite outcomes were included. All-cause or cardiovascular mortality, myocardial infarction (MI), heart failure and stroke were deemed \"hard\" endpoints, whereas hospitalization, angina, and revascularization were identified as \"soft\" endpoints. Type of outcome (primary or secondary), event rates in treatment and control groups for the composite outcome and of its components according to predefined criteria.
Results
Of the 45.8% (316/689) cardiovascular RCTs which utilized a composite outcome, 79.4% set the composite as the primary outcome. Death was the most common component (89.8%), followed by MI (66.1%). About 80% of the trials reported complete data for each component. 147 trials (46.5%) incorporated a \"soft\" endpoint as part of their composite. Death contributed the least to the estimate of effects (R change=0.005) of the composite, while revascularization contributed the most (R change=0.423).
Conclusions
Cardiovascular RCTs frequently employ composite endpoints, which include \"soft\" endpoints as components in nearly 50% of studies. Higher event rates in composite endpoints may create a misleading interpretation of treatment impact due to large contributions from endpoints with less clinical significance.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 13 Sep 2020; epub ahead of print
Shaikh A, Ochani RK, Khan MS, Riaz H, ... Kalra A, Krasuski RA
Am Heart J: 13 Sep 2020; epub ahead of print | PMID: 32941789
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Impact:
Abstract

Underuse of oral anticoagulants in privately insured patients with atrial fibrillation: A population being targeted by the IMplementation of a randomized controlled trial to imProve treatment with oral AntiCoagulanTs in patients with Atrial Fibrillation (IMPACT-AFib).

Al-Khatib SM, Pokorney SD, Al-Khalidi HR, Haynes K, ... Platt R, Granger CB
Background
Many studies showing underuse of oral anticoagulants (OACs) in patients with atrial fibrillation (AF) predated the advent of the non-vitamin K antagonist OACs. We retrospectively examined use of OACs in a large commercially insured population.
Methods
Administrative claims data from 4 research partners participating in FDA-Catalyst, a program of the Sentinel Initiative, were queried in September 2017. Patients were included if they were ≥30 years old with ≥365 days of medical/pharmacy coverage, and had ≥2 diagnosis codes for AF, a CHADS-VASc score ≥2, absence of contraindications to OAC use, and no evidence of OAC use in the 365 days before the index AF diagnosis. The main outcome measures of the current analysis were rates of OAC use in the prior 12 months of cohort identification and factors associated with non-use.
Results
A total of 197,806 AF patients met the eligibility criteria prior to assessment of OAC treatment. Of these, 179,580 (91%) patients were ≥65 years old and 73,286 (37%) patients were ≥80 years old. Half of the patients (98,903) were randomized to the early intervention arm in the IMPACT-AFib trial and constitute the cohort for this analysis. Of these, 32,295 (33%) had no evidence of OAC use in the prior 12 months. Compared with patients with evidence of OAC use in the prior 12 months, patients without OAC use were more likely to be ≥80 years old, women, and have a history of anemia (51% vs 47%) and less likely to have diabetes (41% vs 44%), history of stroke or TIA (15% vs 19%), and history of heart failure (39% vs 48%).
Conclusions
Despite a high risk of stroke, one-third of privately insured patients with AF and no obvious contraindications to an OAC were not treated with an OAC. There is an unmet need for evidence-based interventions that could lead to greater use of OACs in patients with AF at risk for stroke.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 23 Jul 2020; 229:110-117
Al-Khatib SM, Pokorney SD, Al-Khalidi HR, Haynes K, ... Platt R, Granger CB
Am Heart J: 23 Jul 2020; 229:110-117 | PMID: 32949986
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Impact:
Abstract

Geographical Affiliation with Top 10 NIH-Funded Academic Medical Centers and Differences Between Mortality from Cardiovascular Disease and Cancer.

Angraal S, Caraballo C, Kahn P, Bhatnagar A, ... Mamtani R, Ahmad T
Background
Community engagement and rapid translation of findings for the benefit of patients has been noted as a major criterion for NIH decisions regarding allocation of funds for research priorities. We aimed to examine whether the presence of top NIH-funded institutions resulted in a benefit on the cardiovascular and cancer mortality of their local population.
Methods and results
Based on the annual NIH funding of every academic medical from 1995 through 2014, the top 10 funded institutes were identified and the counties where they were located constituted the index group. The comparison group was created by matching each index county to another county which lacks an NIH-funded institute based on sociodemographic characteristics. We compared temporal trends of age-standardized cardiovascular mortality between the index counties and matched counties and states. This analysis was repeated for cancer mortality as a sensitivity analysis. From 1980 through 2014, the annual cardiovascular mortality rates declined in all counties. In the index group, the average decline in cardiovascular mortality rate was 51.5 per 100,000 population (95% CI, 46.8 to 56.2), compared to 49.7 per 100,000 population (95% CI, 45.9 to 53.5) in the matched group (P=0.27). Trends in cardiovascular mortality of the index counties were similar to the cardiovascular mortality trends of their respective states. Cancer mortality rates declined at higher rates in counties with top NIH-funded medical centers (P<0.001).
Conclusions
Cardiovascular mortality rates have decreased with no apparent incremental benefit for communities with top NIH-funded institutions, underscoring the need for an increased focus on implementation science in cardiovascular diseases.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 16 Sep 2020; epub ahead of print
Angraal S, Caraballo C, Kahn P, Bhatnagar A, ... Mamtani R, Ahmad T
Am Heart J: 16 Sep 2020; epub ahead of print | PMID: 32950462
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Impact:
Abstract

Telemedicine in myocarditis: Evolution of a mutidisciplinary \"disease unit\" at the time of COVID-19 pandemic.

Peretto G, De Luca G, Campochiaro C, Palmisano A, ... Esposito A, Sala S

Myocarditis Disease Unit (MDU) is a functional multidisciplinary network designed to offer multidisciplinary assistance to patients with myocarditis. More than 300 patients coming from the whole Country are currently followed up at a specialized multidisciplinary outpatient clinic. Following the pandemic outbreak of the SARS-CoV-2 infection in Italy, we present how the MDU rapidly evolved to a \"tele-MDU\", via a dedicated multitasking digital health platform.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 11 Aug 2020; 229:121-126
Peretto G, De Luca G, Campochiaro C, Palmisano A, ... Esposito A, Sala S
Am Heart J: 11 Aug 2020; 229:121-126 | PMID: 32957030
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Impact:
Abstract

Tobacco smoking in patients with heart failure and coronary artery disease: A 20-year experience at Duke University medical center.

Grubb AF, Pumill CA, Greene SJ, Wu A, Chiswell K, Mentz RJ

Smoking is associated with incident heart failure (HF), yet limited data are available exploring the association between smoking status and long-term outcomes in HF with reduced vs. preserved ejection fraction (i.e., HFrEF vs. HFpEF).
Methods
We performed a retrospective analysis of HF patients undergoing coronary angiography from 1990-2010. Patients with coronary artery disease (CAD) and HF were stratified by EF (< 50% vs. ≥50%), smoking status (prior/current vs. never smoker), and level of smoking (light/moderate vs. heavy). Time-from-catheterization-to-event was examined using Cox proportional hazard modeling for all-cause mortality (ACM), ACM/myocardial infarction/stroke (MACE), and ACM/HF hospitalization with testing for interaction by HF-type (HFrEF vs. HFpEF).
Results
Of 14,406 patients with CAD and HF, 85% (n=12,326) had HFrEF and 15% (n=2080) had HFpEF. At catheterization, 61% of HFrEF and 57% of HFpEF patients had a smoking history. After adjustment, there was a significant interaction between HF-type and the association between smoking status and MACE (interaction P=.009). Smoking history was associated with increased risk for MACE in patients with HFrEF (adjusted hazard ratio [HR] 1.18 [1.12-1.24]), but not HFpEF (HR 1.01 [0.90-1.12]). Active smokers had increased mortality following adjustment compared to former smokers regardless of HF-type (HFrEF HR 1.19 [1.06-1.32], HFpEF HR 1.30 [1.02-1.64], interaction P=.50). Heavy smokers trended towards increased risk of adverse outcomes versus light/moderate smokers; these findings were consistent across HF-type (interaction P>.12).
Conclusion
Smoking history was independently associated with worse outcomes in HFrEF but not HFpEF. Regardless of HF-type, current smokers had higher risk than former smokers.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 23 Sep 2020; epub ahead of print
Grubb AF, Pumill CA, Greene SJ, Wu A, Chiswell K, Mentz RJ
Am Heart J: 23 Sep 2020; epub ahead of print | PMID: 32980363
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Impact:
Abstract

Ultra-low-dose quadruple combination blood pressure lowering therapy in patients with hypertension: The QUARTET randomized controlled trial protocol.

Chow CK, Atkins ER, Billot L, Chalmers J, ... Webster R, Rodgers A

High blood pressure is the leading cause of preventable morbidity and mortality globally. Many patients remain on single-drug treatment with poor control although guidelines recognize that most require combination therapy for blood pressure control. Our hypothesis is that a single-pill combination of four blood pressure- lowering agents each at a quarter dose may provide a simple, safe and effective blood pressure lowering solution which may also improve long term-adherence. The QUARTET (Quadruple UltrA-low-dose tReaTment for hypErTension) double-blind, active controlled, randomized clinical trial will examine whether ultra-low-dose quadruple combination therapy is more effective than guideline recommended standard care, in lowering blood pressure. QUARTET will enroll 650 participants with high blood pressure, either on no treatment or on monotherapy. Participants will be randomized 1:1 and allocated to intervention therapy of a single pill (quadpill) containing irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg and bisoprolol 2.5 mg or to control therapy of a single identical appearing pill containing irbesartan 150 mg. In both arms step up therapy of open-label amlodipine 5mg will be provided if BP is >140/90 at 6weeks. The primary outcome is the difference between groups in the change from baseline in mean unattended automated office systolic blood pressure at 12weeks follow-up. The primary outcome and some secondary outcomes will be assessed at 12weeks, there is an optional 12months extension phase to assess longer term efficacy and tolerability. Our secondary aims are to assess if this approach is safe, has fewer adverse effects and better tolerability compared to standard care control. QUARTET will therefore provide evidence for the effectiveness and safety of a new paradigm in the management of high blood pressure.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 01 Oct 2020; epub ahead of print
Chow CK, Atkins ER, Billot L, Chalmers J, ... Webster R, Rodgers A
Am Heart J: 01 Oct 2020; epub ahead of print | PMID: 33017580
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Impact:
Abstract

Design and Rationale of the XIENCE Short DAPT Clinical Program: an Assessment of the Safety of 3-month or 1-month DAPT in Patients at High Bleeding Risk Undergoing PCI with an Everolimus-Eluting Stent.

Valgimigli M, Cao D, Makkar RR, Bangalore S, ... Wang J, Mehran R

Dual antiplatelet therapy (DAPT) is key for the prevention of recurrent ischemic events after percutaneous coronary intervention (PCI), however, it increases the risk of bleeding complications. While new generation drug-eluting stents have been shown superior to bare-metal stents after a short DAPT course, the optimal DAPT duration in patients at high bleeding risk (HBR) remains to be determined. TRIAL Design: The XIENCE Short DAPT program consists of three prospective, single-arm studies (XIENCE 90, XIENCE 28 Global and XIENCE 28 USA) investigating 3- or 1-month DAPT durations in HBR patients undergoing PCI with the XIENCE stent. The XIENCE 90 study is being conducted in the US and enrolled 2047 subjects who discontinued DAPT at 3months if they were free from myocardial infarction (MI), repeat coronary revascularization, stroke, or stent thrombosis. The XIENCE 28 program includes the USA study, enrolling 642 patients in US and Canada, and the Global study, enrolling 963 patients in Europe and Asia. In XIENCE 28, patients were to discontinue DAPT at 1month post-PCI if event-free. The primary hypothesis for both XIENCE 90 and XIENCE 28 is that a short DAPT regimen will be non-inferior to a conventional DAPT duration with respect to the composite of all-cause death or MI. Patients enrolled in the prospective multicenter post-market XIENCE V USA study will be used as historical control group in a stratified propensity-adjusted analysis. Conclusions: The XIENCE Short DAPT Program will provide insights into the safety and efficacy of two abbreviated DAPT regimens of 3- and 1-month duration in a large cohort of HBR patients undergoing PCI with the XIENCE stent.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 04 Oct 2020; epub ahead of print
Valgimigli M, Cao D, Makkar RR, Bangalore S, ... Wang J, Mehran R
Am Heart J: 04 Oct 2020; epub ahead of print | PMID: 33031789
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Impact:
Abstract

Association between intensive care unit utilization for patients with non-ST segment elevation myocardial infarction and patient experience.

Fanaroff AC, Chen AY, van Diepen S, Mylod D, Peterson ED, Wang TY

Routine intensive care unit (ICU) utilization for patients with initially stable non-ST segment elevation myocardial infarction is not associated with improved short- or long-term patient outcomes; however, the association with patient experience has not been reported. Using Hospital Consumer Assessment of Healthcare Providers and Systems patient survey data linked to ICU use data from the National Cardiovascular Data Registry, we found no association between hospital-level ICU utilization and metrics of patient experience, including communication, staff responsiveness, and overall satisfaction.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 08 Oct 2020; epub ahead of print
Fanaroff AC, Chen AY, van Diepen S, Mylod D, Peterson ED, Wang TY
Am Heart J: 08 Oct 2020; epub ahead of print | PMID: 33045223
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Impact:
Abstract

Rationale and design of ApoA-I event reducing in ischemic syndromes II (AEGIS-II): A phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group study to investigate the efficacy and safety of CSL112 in subjects after acute myocardial infarction.

Gibson CM, Kastelein JJP, Phillips AT, Aylward PE, ... Ridker P, Mehran R

Acute myocardial infarction (AMI) patients remain at high risk for recurrent events. Cholesterol efflux, mediated by apolipoprotein A-I (apoA-I), removes excess cholesterol from atherosclerotic plaque and transports it to the liver for excretion. Impaired cholesterol efflux is associated with higher cardiovascular (CV) event rates among both patients with stable coronary artery disease (CAD) and recent myocardial infarction (MI). CSL112, a novel intravenous formulation of apoA-I (Human) derived from human plasma, increases cholesterol efflux capacity. AEGIS-II is a phase 3, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial investigating the efficacy and safety of CSL112 compared to placebo among high-risk AMI participants. Eligibility criteria include age≥18years with type 1 (spontaneous) MI, evidence of multivessel CAD, and presence of diabetes requiring pharmacotherapy, or≥2 of the following: age≥65years, prior MI or peripheral artery disease. A target sample of 17,400 participants will be randomized 1:1 to receive 4 weekly infusions of CSL112 6g or placebo, initiated prior to or on the day of discharge and within 5days of first medical contact. The primary outcome is the time to first occurrence of the composite of CV death, MI, or stroke through 90days. Key secondary outcomes include the total number of hospitalizations for coronary, cerebral, or peripheral ischemia through 90days, and time to first occurrence of the composite primary outcome through 180 and 365days. AEGIS-II will be the first trial to formally test whether enhancing cholesterol efflux can reduce the rate of recurrent major adverse CV events.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 12 Oct 2020; epub ahead of print
Gibson CM, Kastelein JJP, Phillips AT, Aylward PE, ... Ridker P, Mehran R
Am Heart J: 12 Oct 2020; epub ahead of print | PMID: 33065120
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Impact:
Abstract

National trends and 30-day readmission rates for next-day-discharge TAVR: An analysis from the Nationwide readmissions database, 2012-2016.

Yerasi C, Tripathi B, Wang Y, Forrestal BJ, ... Rogers T, Waksman R
Background
Transcatheter aortic valve replacement (TAVR) has evolved toward a minimalist approach, resulting in shorter hospital stays. Real-world trends of next-day discharge (NDD) TAVR are unknown. This study aimed to evaluate underlying trends and readmissions of NDD-TAVR.
Methods
This study was derived from the Nationwide Readmissions Database (NRD) from 2012 to 2016. International Classification of Diseases, Ninth and Tenth revisions, codes were used to identify patients. Any discharge within 1day of admission was identified as NDD. NDD-TAVR trends over the years were analyzed, and any admissions within 30days were considered readmissions. A hierarchical logistic regression model was used to identify predictors of readmission.
Results
Of 49,742 TAVR procedures, 3104 were NDD. The percentage of NDD-TAVR increased from 1.5% (46/3051) in 2012 to 12.2% (2393/19,613) in 2016. However, the 30-day readmission rate remained the same over the years (8.6%). The patients\' mean age was 80.3±8.4years. Major readmission causes were heart-failure exacerbation (16%), infections (9%), and procedural complications (8%). In 2016, there were significantly higher late conduction disorder and gastrointestinal bleeding readmission rates than in 2012-2015. Significant predictors of readmission were anemia, baseline conduction disease, cardiac arrhythmias, heart failure, chronic kidney disease, chronic obstructive pulmonary disease, neoplastic disorders, and discharge to facility.
Conclusions
The percentage of NDD-TAVR increased over the years; however, readmission rates remained the same, with a higher rate of conduction abnormality-related hospitalizations in 2016. Careful discharge planning that includes identification of baseline factors that predict readmission and knowledge of etiologies may further prevent 30-day readmissions.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 18 Oct 2020; epub ahead of print
Yerasi C, Tripathi B, Wang Y, Forrestal BJ, ... Rogers T, Waksman R
Am Heart J: 18 Oct 2020; epub ahead of print | PMID: 33091365
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Abstract

Lipid temporal trends in Normal weight youth.

Zachariah JP, Shittu T, Wang Y
Background
Atherosclerosis begins in youth, partly driven by excess weight(EW) and abnormal lipids. Despite pediatric obesity worsening, lipids improved.Given the relation between EW and abnormal lipids, changes in normal weight (NW) youth may be relevant. We examined the proportions and temporal trendsof youth with abnormal lipids who were NW versus EW.
Methods and results
Analysis was done from National Health and Nutrition Examination Surveys (NHANES)1988-2016. Data was extracted for 10-20year olds measured with anthropometrics and lab testing to determine proportions of NW versus EW with total cholesterol(TC) >190 mg/dL, high density lipoprotein cholesterol (HDL-C) <40 mg/dL, and calculated non-HDL-C>145mg/dL (N=14,785). In survey-weighted regression analysis, a weight-status interaction term was used to examine effect modification in the lipid temporal trend. Over time, EW prevalence increased while dyslipidemia decreased (trend p value <.001 for both). For the pooled sample, EW more than doubled the risk of each lipid disorder(P<.0001 for each). However for each abnormal lipid, 26-63% were NW. As the temporal trend in abnormal lipids declined, the proportion with abnormal lipids who were NW also declined. On regression analysis, temporal declines in NW and EW differed for HDL-C.
Conclusions
NW constituted more than a quarter to half of youth with abnormal lipids. Over time, youth with abnormal lipids were less often NW. The novel observation that a high proportion of youth with abnormal lipids who are NW is relevant to debates on universal lipid screening, the focus on weight reduction in youth lipid management, and conventional wisdom in cardiometabolic health.

Copyright © 2020 Elsevier Inc. All rights reserved.

Am Heart J: 19 Oct 2020; epub ahead of print
Zachariah JP, Shittu T, Wang Y
Am Heart J: 19 Oct 2020; epub ahead of print | PMID: 33096104
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Abstract

Statins and atherosclerotic cardiovascular outcomes in patients on incident dialysis and with atherosclerotic heart disease.

Shavadia JS, Wilson J, Edmonston D, Platt A, ... Pendergast J, Scialla JJ
Background
Statins failed to reduce cardiovascular (CV) events in trials of patients on dialysis. However, trial populations used criteria that often excluded those with atherosclerotic heart disease (ASHD), in whom statins have the greatest benefit, and included outcome composites with high rates of non-atherosclerotic CV events that may not be modified by statins. Here, we study whether statin use associates with lower atherosclerotic CV risk among patients with known ASHD on dialysis, including in those likely to receive a kidney transplant, a group excluded within trials, but with lower competing mortality risks.
Methods
Using data from the United States Renal Data System including Medicare claims, we identified adults initiating dialysis with ASHD. We matched statin users 1:1 to statin nonusers with propensity scores incorporating hard matches for age and kidney transplant listing status. Using Cox models, we evaluated associations of statin use with the primary composite of fatal/non-fatal myocardial infarction and stroke (including within pre-specified subgroups of younger age (<50years) and waitlisting status); secondary outcomes included all-cause mortality, and composite of all-cause mortality, non-fatal myocardial infarction or stroke.
Results
Of 197,716 patients with ASHD, 47,562 (24%) were consistent statin users from which we created 46,186 matched pairs. Over a median 662days, statin users had similar risk of fatal/non-fatal myocardial infarction or stroke overall (HR 1.00, 95% CI 0.97, 1.02), or in subgroups [age<50years (HR=1.05, 95% CI 0.95, 1.17); waitlisted for kidney transplant (HR 0.99, 95% CI 0.97, 1.02)]. Statin use was modestly associated with lower all-cause mortality (HR 0.96, 95% CI 0.94, 0.98; E-value =1.21) and similarly, a modest lower composite risk of all-cause mortality, non-fatal myocardial infarction or stroke over the first two years (HR 0.90, 95% CI 0.88, 0.91), but attenuated thereafter (HR 0.98, 95% CI 0.96, 1.01).
Conclusions
Our large observational analyses are consistent with trials in more selected populations and suggest that statins may not meaningfully reduce atherosclerotic CV events even among incident dialysis patients with established ASHD and those likely to receive kidney transplants.

Copyright © 2020. Published by Elsevier Inc.

Am Heart J: 19 Oct 2020; epub ahead of print
Shavadia JS, Wilson J, Edmonston D, Platt A, ... Pendergast J, Scialla JJ
Am Heart J: 19 Oct 2020; epub ahead of print | PMID: 33096103
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This program is still in alpha version.