Journal: JACC Heart Fail

Sorted by: date / impact
Abstract

The REDUCE FMR Trial: A Randomized Sham-Controlled Study of Percutaneous Mitral Annuloplasty in Functional Mitral Regurgitation.

Witte KK, Lipiecki J, Siminiak T, Meredith IT, ... Kaye DM, Sievert H
Objectives
This study sought to evaluate the effects of the Carillon device on mitral regurgitation severity and left ventricular remodeling.
Background
Functional mitral regurgitation (FMR) complicates heart failure with reduced ejection fraction and is associated with a poor prognosis.
Methods
In this blinded, randomized, proof-of-concept, sham-controlled trial, 120 patients receiving optimal heart failure medical therapy were assigned to a coronary sinus-based mitral annular reduction approach for FMR or sham. The pre-specified primary endpoint was change in mitral regurgitant volume at 12 months, measured by quantitative echocardiography according to an intention-to-treat analysis.
Results
Patients (69.8 ± 9.5 years of age) were randomized to either the treatment (n = 87) or the sham-controlled (n = 33) arm. There were no significant differences in baseline characteristics between the groups. In the treatment group, 73 of 87 (84%) had the device implanted. The primary endpoint was met, with a statistically significant reduction in mitral regurgitant volume in the treatment group compared to the control group (decrease of 7.1 ml/beat [95% confidence interval [CI]: -11.7 to -2.5] vs. an increase of 3.3 ml/beat [95% CI: -6.0 to 12.6], respectively; p = 0.049). Additionally, there was a significant reduction in left ventricular volumes in patients receiving the device versus those in the control group (left ventricular end-diastolic volume decrease of 10.4 ml [95% CI: -18.5 to -2.4] vs. an increase of 6.5 ml [95% CI: -5.1 to 18.2]; p = 0.03 and left ventricular end-systolic volume decrease of 6.2 ml [95% CI: -12.8 to 0.4] vs. an increase of 6.1 ml [95% CI: -1.42 to 13.6]; p = 0.04).
Conclusions
The Carillon device significantly reduced mitral regurgitant volume and left ventricular volumes in symptomatic patients with functional mitral regurgitation receiving optimal medical therapy. (Carillon Mitral Contour System for Reducing Functional Mitral Regurgitation [REDUCE FMR]; NCT02325830).

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Oct 2019; 7:945-955
Witte KK, Lipiecki J, Siminiak T, Meredith IT, ... Kaye DM, Sievert H
JACC Heart Fail: 30 Oct 2019; 7:945-955 | PMID: 31521683
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Design of a \"Lean\" Case Report Form for Heart Failure Therapeutic Development.

Psotka MA, Fiuzat M, Carson PE, Kao DP, ... O\'Connor CM, Abraham WT

The development of treatments for heart failure (HF) is challenged by burdensome clinical trials. Reducing the need for extensive data collection and increasing opportunities for data compatibility between trials may improve efficiency and reduce resource burden. The Heart Failure Collaboratory (HFC) multi-stakeholder consortium sought to create a lean case report form (CRF) for use in HF clinical trials evaluating cardiac devices. The HFC convened patients, clinicians, clinical researchers, the U.S. Food and Drug Administration (FDA), payers, industry partners, and statisticians to create a consensus core CRF. Eight recent clinical trial CRFs for the treatment of HF from 6 industry partners were analyzed. All CRF elements were systematically reviewed. Those elements deemed critical for data collection in HF clinical trials were used to construct the final, harmonized CRF. The original CRFs included 176 distinct data items covering demographics, vital signs, physical examination, medical history, laboratory and imaging testing, device therapy, medications, functional and quality of life assessment, and outcome events. The resulting, minimally inclusive CRF device contains 75 baseline data items and 6 events, with separate modular additions that can be used depending on the additional detail required for a particular intervention. The consensus electronic form is now freely available for use in clinical trials. Creation of a core CRF is important to improve clinical trial efficiency in HF device development in the United States. This living document intends to reduce clinical trial administrative burden, increase evidence integrity, and improve comparability of clinical data between trials.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Oct 2019; 7:913-921
Psotka MA, Fiuzat M, Carson PE, Kao DP, ... O'Connor CM, Abraham WT
JACC Heart Fail: 30 Oct 2019; 7:913-921 | PMID: 31401097
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

HFpEF Is the Substrate for Stroke in Obesity and Diabetes Independent of Atrial Fibrillation.

Packer M

Both obesity and type 2 diabetes are important risk factors for the development of heart failure with a preserved ejection fraction (HFpEF), and both disorders increase the risk of systemic thromboembolic events. Traditionally, the risk of stroke has been explained by the strong association of these disorders with atrial fibrillation (AF). However, adiposity and diabetes are risk factors for systemic thromboembolism, even in the absence of AF, because both can lead to the development of an inflammatory and fibrotic atrial and ventricular myopathy, the 2 major elements of HFpEF. Atrial myopathy: 1) exacerbates pulmonary venous hypertension and exertional dyspnea; 2) leads to decreased flow, thrombogenesis, and systemic thromboembolization; and 3) often clinically manifests as AF; however, the relationship between AF and thromboembolism is unclear. Atrial fibrosis predisposes to thrombus formation, even in the absence of AF, and most thromboembolic events bear a poor temporal relationship to the occurrence of AF, whereas HFpEF (and the accompanying atrial disease) predicts stroke in patients with or without AF. Furthermore, rhythm control does not reduce the risk of stroke, although it reduces the burden of AF. These observations support the primacy of atrial myopathy as a critical component of HFpEF, rather than AF, as the mediator of systemic thromboembolism in obesity or diabetes. The well-established association between AF and stroke is likely explained by the fact that AF is a biomarker of more advanced inflammatory atrial disease but not necessarily a direct causal mechanism.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 03 Nov 2019; epub ahead of print
Packer M
JACC Heart Fail: 03 Nov 2019; epub ahead of print | PMID: 31706838
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Hyperkalemia and Treatment With RAAS Inhibitors During Acute Heart Failure Hospitalizations and Their Association With Mortality.

Beusekamp JC, Tromp J, Cleland JGF, Givertz MM, ... Voors AA, van der Meer P
Objectives
This study investigated associations between incident hyperkalemia during acute heart failure (HF) hospitalizations and changes in renin-angiotensin-aldosterone system (RAAS) inhibitors.
Background
Hyperkalemia is a potential complication of RAAS inhibitors. For patients with HF, fear of hyperkalemia may lead to failure to deliver guideline-recommended doses of RAAS inhibitors.
Methods
Serum potassium concentrations were measured daily from baseline (<24 h after admission) until discharge or day 7 in 1,589 patients enrolled in the PROTECT (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function) trial. Incident hyperkalemia was defined as at least 1 episode of potassium >5.0 mEq/l. The primary outcome was all-cause mortality at 180 days.
Results
Overall, serum potassium concentrations increased from 4.3 ± 0.6 mEq/l at baseline to 4.5 ± 0.6 mEq/l at discharge or day 7 (p < 0.001). Patients developing incident hyperkalemia (n = 564; 35%) were more often taking mineralocorticoid antagonists (MRAs) therapy prior to hospitalization and were more likely to have them down-titrated during hospitalization, independent of confounders. Incident hyperkalemia was not associated with adverse outcomes. Yet, down-titration of MRAs during hospitalization was independently associated with 180-day mortality (hazard ratio [HR]: 1.73; 95% confidence interval [CI]: 1.15 to 2.60), regardless of incident hyperkalemia (p >0.10). Patients with incident hyperkalemia who were discharged with the same or increased dose of MRAs (HR: 0.52; 95% CI: 0.32 to 0.85) or angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs) (HR: 0.47; 95% CI: 0.29 to 0.77) had a lower 180-day mortality.
Conclusions
Incident hyperkalemia is common in patients hospitalized for acute HF and is not associated with adverse outcomes. Incident hyperkalemia is associated with down-titration of MRAs, but patients who maintained or increased their dose of MRAs and/or ACE inhibitors/ARB during acute HF hospitalization had better 180-day survival.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Oct 2019; 7:970-979
Beusekamp JC, Tromp J, Cleland JGF, Givertz MM, ... Voors AA, van der Meer P
JACC Heart Fail: 30 Oct 2019; 7:970-979 | PMID: 31606364
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Representativeness of a Heart Failure Trial by Race and Sex: Results From ASCEND-HF and GWTG-HF.

Greene SJ, DeVore AD, Sheng S, Fonarow GC, ... O\'Connor CM, Mentz RJ
Objectives
This study sought to determine the degree to which U.S. patients enrolled in a heart failure (HF) trial represent patients in routine U.S. clinical practice according to race and sex.
Background
Black patients and women are frequently under-represented in HF clinical trials. However, the degree to which black patients and women enrolled in trials represent such patients in routine practice is unclear.
Methods
The ASCEND-HF (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) trial randomized patients hospitalized for HF to receive nesiritide or placebo from May 2007 to August 2010 and was neutral for clinical endpoints. This analysis compared non-Hispanic white (n = 1,494) and black (n = 1,012) patients enrolled in ASCEND-HF from the U.S. versus non-Hispanic white and black patients included in a U.S. hospitalized HF registry (i.e., Get With The Guidelines-Heart Failure [GWTG-HF]) during the ASCEND-HF enrollment period and meeting trial eligibility criteria.
Results
Among 79,291 white and black registry patients, 49,063 (62%) met trial eligibility criteria (white, n = 37,883 [77.2%]; black, n = 11,180 [22.8%]). Women represented 35% and 49% of the ASCEND-HF and trial-eligible GWTG-HF cohorts, respectively. Compared with trial-enrolled patients, trial-eligible GWTG-HF patients tended to be older with higher blood pressure and higher ejection fraction. Trial-eligible patients had higher in-hospital mortality (2.3% vs. 1.3%), 30-day readmission (20.2% vs. 16.8%), and 180-day mortality (21.2% vs. 18.6%) than those enrolled in the trial (all p < 0.02), with consistent mortality findings by race and sex. After propensity score matching, mortality rates were similar; however, trial-eligible patients continued to have higher rates of 30-day readmission (23.1% vs. 17.3%; p < 0.01), driven by differences among black patients and women (all p for interaction ≤0.02).
Conclusions
Patients with HF seen in U.S. practice and eligible for the ASCEND-HF trial had worse clinical outcomes than those enrolled in the trial. After accounting for clinical characteristics, trial-eligible real-world patients continued to have higher rates of 30-day readmission, driven by differences among black patients and women. Social, behavioral, and other unmeasured factors may impair representativeness of patients enrolled in HF trials, particularly among racial/ethnic minorities and women. (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure [ASCEND-HF]; NCT00475852).

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Oct 2019; 7:980-992
Greene SJ, DeVore AD, Sheng S, Fonarow GC, ... O'Connor CM, Mentz RJ
JACC Heart Fail: 30 Oct 2019; 7:980-992 | PMID: 31606362
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The Future of Wearables in Heart Failure Patients.

DeVore AD, Wosik J, Hernandez AF

The adoption of mobile health (mHealth) devices is creating a unique opportunity to improve heart failure (HF) care. The rise of mHealth is driven by multiple factors including consumerism, policy changes in health care, and innovations in technology. Wearable health devices are one aspect of mHealth that may improve the delivery of HF care by allowing for medical data collection outside of a clinician\'s office or hospital. Wearable devices are externally applied and capture functional or physiological data in order to monitor and improve patients\' health. Most wearable sensors capture data continuously and may be incorporated into accessories (e.g., a watch or clothing) or may be applied as a cutaneous patch. Wearable devices are often paired with another device, such as a smartphone, to collect, interpret, or transmit data. This study assessed the potential applications of wearable devices in HF care, summarizes available data for wearables, and discusses the future of wearables for improving the health of patients with HF.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Oct 2019; 7:922-932
DeVore AD, Wosik J, Hernandez AF
JACC Heart Fail: 30 Oct 2019; 7:922-932 | PMID: 31672308
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Pregnant women with Uncorrected Congenital Heart Disease: Heart failure and mortality.

Sliwa K, Baris L, Sinning C, Zengin-Sahm E, ... Hall R, Roos-Hesselink J
Background
Globally, congenital heart disease (CHD) is an important cause of maternal morbidity and mortality in women reaching reproductive stage. There is lack of data from larger cohorts of women with uncorrected CHD.
Objectives
To study maternal and fetal outcome of women with uncorrected CHD.
Methods
An analysis of 10-year data from the ESC EORP ROPAC Registry of women with uncorrected CHD.
Results
Of a total of 5739 pregnancies in 53 countries, 3295 women had CHD, with 1059 uncorrected. Of these, 41.4 % were from emerging countries. There were marked differences in cardiac defects in uncorrected versus corrected CHD with primary shunt lesions (44.7% vs 32.4%), valvular abnormalities (33.5% vs 12.6%) and Tetralogy of Fallot/Pulmonary atresia (0.8% vs 20.3%), p<0.001. In uncorrected CHD 6.8% were in mWHO risk class IV, about 10 % had pulmonary hypertension (PH) and 3% were cyanotic prior to pregnancy. Maternal mortality and heart failure (HF) in the women with uncorrected CHD was 0.7% and 8.7%. Eisenmenger syndrome was associated with a very high risk of cardiac events (65.5%), maternal mortality (10.3%) and HF (48.3%). Coming from an emerging country was associated with higher pre-pregnancy signs of HF, PH and cyanosis (p<0.001) and worse maternal and fetal outcomes, with a threefold higher rate of hospital admissions for cardiac events and intrauterine growth retardation (p<0.001).
Conclusions
We found marked differences in cardiac conditions in pregnant women with uncorrected CHD versus corrected CHD, with a markedly worse outcome, particularly in women with Eisenmenger syndrome and from emerging countries.

Copyright © 2019. Published by Elsevier Inc.

JACC Heart Fail: 06 Sep 2019; epub ahead of print
Sliwa K, Baris L, Sinning C, Zengin-Sahm E, ... Hall R, Roos-Hesselink J
JACC Heart Fail: 06 Sep 2019; epub ahead of print | PMID: 31511192
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association Between Sacubitril/Valsartan Initiation and Health Status Outcomes in Heart Failure With Reduced Ejection Fraction.

Khariton Y, Fonarow GC, Arnold SV, Hellkamp A, ... McCague K, Spertus JA
Objectives
This study sought to describe the short-term health status benefits of angiotensin-neprilysin inhibitor (ARNI) therapy in patients with heart failure and reduced ejection fraction (HFrEF).
Background
Although therapy with sacubitril/valsartan, a neprilysin inhibitor, improved patients\' health status (compared with enalapril) at 8 months in the PARADIGM-HF (Prospective Comparison of ARNI with ACE inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study, the early impact of ARNI on patients\' symptoms, functions, and quality of life is unknown.
Methods
Health status was assessed by using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ) in 3,918 outpatients with HFrEF and left ventricular ejection fraction ≤40% across 140 U.S. centers in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry. ARNI therapy was initiated in 508 patients who were matched 1:2 to 1,016 patients who were not initiated on ARNI (no-ARNI), using a nonparsimonious time-dependent propensity score (6 sociodemographic factors, 23 clinical characteristics), prior KCCQ overall summary (KCCQ-OS) score, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker status.
Results
Multivariate linear regression demonstrated a greater mean improvement in KCCQ-OS in patients initiated on ARNI therapy (5.3 ± 19 vs. 2.5 ± 17.4, respectively; p < 0.001) over a median (interquartile range [IQR]) of 57 (32 to 104) days. The proportions of ARNI versus no-ARNI groups with ≥10-point (large) and ≥20-point (very large) improvements in KCCQ-OS were 32.7% versus 26.9%, respectively, and 20.5% versus 12.1%, respectively, consistent with numbers needed to treat of 18 and 12, respectively.
Conclusions
In routine clinical care, ARNI therapy was associated with early improvements in health status, with 20% experiencing a very large health status benefit compared with 12% who were not started on ARNI therapy. These findings support the use of ARNI to improve patients\' symptoms, functions, and quality of life.

Published by Elsevier Inc.

JACC Heart Fail: 30 Oct 2019; 7:933-941
Khariton Y, Fonarow GC, Arnold SV, Hellkamp A, ... McCague K, Spertus JA
JACC Heart Fail: 30 Oct 2019; 7:933-941 | PMID: 31521679
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prescribing Patterns of Heart Failure-Exacerbating Medications Following a Heart Failure Hospitalization.

Goyal P, Kneifati-Hayek J, Archambault A, Mehta K, ... Maurer MS, Safford MM
Objectives
This study sought to describe the patterns of heart failure (HF)-exacerbating medications used among older adults hospitalized for HF and to examine determinants of HF-exacerbating medication use.
Background
HF-exacerbating medications can potentially contribute to adverse outcomes and could represent an important target for future strategies to improve post-hospitalization outcomes.
Methods
Medicare beneficiaries ≥65 years of age with an adjudicated HF hospitalization between 2003 and 2014 were derived from the geographically diverse REGARDS (Reasons for Geographic and Racial Difference in Stroke) cohort study. Major HF-exacerbating medications, defined as those listed on the 2016 American Heart Association Scientific Statement listing medications that can precipitate or induce HF, were examined. Patterns of prescribing medications at hospital admission and at discharge were examined, as well as changes that occurred between admission and discharge; and a multivariable logistic regression analysis was conducted to identify determinants of harmful prescribing practices following HF hospitalization (defined as either the continuation of an HF-exacerbating medications or an increase in the number of HF-exacerbating medications between hospital admission and discharge).
Results
Among 558 unique individuals, 18% experienced a decrease in the number of HF-exacerbating medications between admission and discharge, 19% remained at the same number, and 12% experienced an increase. Multivariable logistic regression analysis revealed that diabetes (odds ratio [OR]: 1.80; 95% confidence interval [CI]: 1.18 to 2.75]) and small hospital size (OR: 1.93; 95% CI: 1.18 to 3.16) were the strongest, independently associated determinants of harmful prescribing practices.
Conclusions
HF-exacerbating medication regimens are often continued or started following an HF hospitalization. These findings highlight an ongoing need to develop strategies to improve safe prescribing practices in this vulnerable population.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 03 Nov 2019; epub ahead of print
Goyal P, Kneifati-Hayek J, Archambault A, Mehta K, ... Maurer MS, Safford MM
JACC Heart Fail: 03 Nov 2019; epub ahead of print | PMID: 31706836
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

A Changing Landscape of Mortality for Systemic Light Chain Amyloidosis.

Barrett CD, Dobos K, Liedtke M, Tuzovic M, ... Schrier S, Witteles RM
Objectives
The purpose of this study was to address the overall trends in mortality since the adoption of modern therapies for treatment of systemic amyloidosis, and to reconsider the prognostic significance of individual components of the current staging system.
Background
Systemic light chain (AL) amyloidosis involves deposition of immunoglobulin light chains in organs throughout the body and is known to have the highest mortality when significant cardiac involvement is present. Survival has historically been poor but may be improving as systemic therapies continue to advance. This study assesses whether recent advancements in light chain directed therapy have led to improved survival in patients with systemic AL amyloidosis.
Methods
We reviewed all cases of patients who were evaluated for a new diagnosis of AL amyloidosis at the Stanford Amyloid Center between 2009 and 2016. Patients\' stage at diagnosis was determined according to the most commonly used staging system. Clinical data, overall survival from diagnosis, and the independent influence of each component of the staging system were analyzed.
Results
At total of 194 patients were identified with a new diagnosis of systemic AL amyloidosis. Median overall survival was 59 months and 6 months for stage 3 and 4 patients, respectively. Median overall survival was not reached in stage 1 and 2 groups, as survival was >50% by the end of the study. Mean overall survival was 118 months, 76 months, 64 months, and 27 months in Stages 1, 2, 3, and 4 patients, respectively. Although N-terminal pro-B-type natriuretic peptide and troponin I concentrations had large effects on prognosis, differences in serum free light chains (dFLC) on initial staging laboratory results ≥18 mg/dl, part of the current staging system, did not contribute significantly to prognosis for values ≥5 mg/dl.
Conclusions
Survival for patients with systemic AL amyloidosis has improved for patients at all stages of disease in the present era of rapid advancements in light chain-reducing therapies. Cardiac biomarkers at diagnosis, but not baseline dFLC ≥18 mg/dl, continue to provide important prognostic information.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Oct 2019; 7:958-966
Barrett CD, Dobos K, Liedtke M, Tuzovic M, ... Schrier S, Witteles RM
JACC Heart Fail: 30 Oct 2019; 7:958-966 | PMID: 31606365
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Healthy Aging and Cardiovascular Function: Invasive Hemodynamics During Rest and Exercise in 104 Healthy Volunteers.

Pandey A, Kraus WE, Brubaker PH, Kitzman DW
Objectives
The aim of this study was to evaluate the association between age and invasive cardiovascular hemodynamics during upright exercise among healthy adults.
Background
The marked age-related decline in maximal exercise oxygen uptake (peak VO) may contribute to the high burden of heart failure among older individuals and their greater severity of exertional symptoms. However, the mechanisms underlying this decline are not well understood.
Methods
A total of 104 healthy community-dwelling volunteers age 20 to 76 years well screened for cardiovascular disease underwent exhaustive upright exercise with brachial and pulmonary artery catheters; radionuclide ventriculography; and expired gas analysis for the measurement of peak VO, cardiac output, left ventricular stroke volume, end-diastolic volume, end-systolic volume, ejection fraction, pulmonary capillary wedge pressure, and arteriovenous oxygen difference.
Results
Over a 5.5-decade age range, there was a 40% decline in peak VO due primarily to reduced peak exercise cardiac output; peak arteriovenous oxygen difference was unaffected by age. The lower age-related exercise cardiac output was related to lower peak exercise heart rate and stroke volume. Aging was also associated with lower peak exercise ejection fraction, indicating reduced inotropic reserve. Peak exercise end-diastolic volume was lower with aging despite similar left ventricular filling pressure, suggesting age-related reduced diastolic compliance limiting the use of the Frank-Starling mechanism to compensate for reduced chronotropic and inotropic reserves. These age relationships were unaffected by sex.
Conclusions
The age-related decline in exercise capacity among healthy persons is due predominantly to cardiac mechanisms, including reduced chronotropic and inotropic reserve and possibly reduced Frank-Starling reserve. Peak exercise left ventricular filling pressure and arteriovenous oxygen difference are unchanged with healthy aging.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 03 Nov 2019; epub ahead of print
Pandey A, Kraus WE, Brubaker PH, Kitzman DW
JACC Heart Fail: 03 Nov 2019; epub ahead of print | PMID: 31706837
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Mediators of the Effects of Canagliflozin on Heart Failure in Patients With Type 2 Diabetes.

Li J, Woodward M, Perkovic V, Figtree GA, ... Matthews DR, Neal B
Objectives
The purpose of this study was to explore potential mediators of the effects of canagliflozin on heart failure in the CANVAS Program (CANagliflozin cardioVascular Assessment Study; NCT01032629 and CANagliflozin cardioVascular Assessment Study-Renal; NCT01989754).
Background
Canagliflozin reduced the risk of heart failure among patients with type 2 diabetes in the CANVAS Program. The mechanism of protection is uncertain.
Methods
The percentages of mediating effects of 19 biomarkers were determined by comparing the hazard ratios for the effect of randomized treatment from an unadjusted model and from a model adjusting for the biomarker of interest. Multivariable analyses were used to assess the joint effects of biomarkers that mediated most strongly in univariable analyses.
Results
Early changes after randomization in levels of 3 biomarkers (urinary albumin:creatinine ratio, serum bicarbonate, and serum urate) were identified as mediating the effect of canagliflozin on heart failure. Average post-randomization levels of 14 biomarkers (systolic blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol, total cholesterol, urinary albumin:creatinine ratio, weight, body mass index, gamma glutamyltransferase, hematocrit, hemoglobin concentration, serum albumin, erythrocyte concentration, serum bicarbonate, and serum urate) were identified as significant mediators. Individually, the 3 biomarkers with the largest mediating effect were erythrocyte concentration (45%), hemoglobin concentration (43%), and serum urate (40%). In a parsimonious multivariable model, erythrocyte concentration, serum urate, and urinary albumin:creatinine ratio were the 3 biomarkers that maximized cumulative mediation (102%).
Conclusions
A diverse set of potential mediators of the effect of canagliflozin on heart failure were identified. Some mediating effects were anticipated, whereas others were not. The mediators that were identified support existing and novel hypothesized mechanisms for the prevention of heart failure with sodium glucose cotransporter 2 inhibitors.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 22 Oct 2019; epub ahead of print
Li J, Woodward M, Perkovic V, Figtree GA, ... Matthews DR, Neal B
JACC Heart Fail: 22 Oct 2019; epub ahead of print | PMID: 31676303
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Machine Learning Prediction of Mortality and Hospitalization in Heart Failure with Preserved Ejection Fraction.

Angraal S, Mortazavi BJ, Gupta A, Khera R, ... Spertus JA, Krumholz HM
Objectives
This study sought to develop models for predicting mortality and heart failure (HF) hospitalization for outpatients with HF with preserved ejection fraction (HFpEF) in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial.
Background
Although risk assessment models are available for patients with HF with reduced ejection fraction, few have assessed the risks of death and hospitalization in patients with HFpEF.
Methods
The following 5 methods: logistic regression with a forward selection of variables; logistic regression with a lasso regularization for variable selection; random forest (RF); gradient descent boosting; and support vector machine, were used to train models for assessing risks of mortality and HF hospitalization through 3 years of follow-up and were validated using 5-fold cross-validation. Model discrimination and calibration were estimated using receiver-operating characteristic curves and Brier scores, respectively. The top prediction variables were assessed by using the best performing models, using the incremental improvement of each variable in 5-fold cross-validation.
Results
The RF was the best performing model with a mean C-statistic of 0.72 (95% confidence interval [CI]: 0.69 to 0.75) for predicting mortality (Brier score: 0.17), and 0.76 (95% CI: 0.71 to 0.81) for HF hospitalization (Brier score: 0.19). Blood urea nitrogen levels, body mass index, and Kansas City Cardiomyopathy Questionnaire (KCCQ) subscale scores were strongly associated with mortality, whereas hemoglobin level, blood urea nitrogen, time since previous HF hospitalization, and KCCQ scores were the most significant predictors of HF hospitalization.
Conclusions
These models predict the risks of mortality and HF hospitalization in patients with HFpEF and emphasize the importance of health status data in determining prognosis. (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist [TOPCAT]; NCT00094302).

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 04 Oct 2019; epub ahead of print
Angraal S, Mortazavi BJ, Gupta A, Khera R, ... Spertus JA, Krumholz HM
JACC Heart Fail: 04 Oct 2019; epub ahead of print | PMID: 31606361
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Diagnostic and Therapeutic Gaps in Patients With Heart Failure and Chronic Obstructive Pulmonary Disease.

Canepa M, Franssen FME, Olschewski H, Lainscak M, ... Tavazzi L, Rosenkranz S

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) coincide in a significant number of patients. Recent population-based registries suggest that spirometry is largely underused in patients with HF to diagnose comorbid COPD and that patients with COPD frequently do not receive the recommended beta-blocker (BB) treatment. This state-of-the-art review summarizes: 1) current challenges in the implementation of recommended spirometry for COPD diagnosis in patients with HF; and 2) current underuse and underdosing of BBs in patients with HF and COPD despite guideline recommendations. Open issues in the therapeutic management of patients with HF and COPD are discussed in the third section, including the use of the nonselective BB carvedilol, target BB doses in patients with HF and COPD, BB and bronchodilator management during HF hospitalization with and without COPD exacerbation, and the use of BBs in patients with COPD with right HF or free from cardiovascular disease. The whole scenario described herein advocates for a bipartisan initiative to drive immediate attention to the translation of guideline recommendations into clinical practice for patients with HF with co-occurring COPD.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Sep 2019; 7:823-833
Canepa M, Franssen FME, Olschewski H, Lainscak M, ... Tavazzi L, Rosenkranz S
JACC Heart Fail: 29 Sep 2019; 7:823-833 | PMID: 31521680
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

MRAs in Elderly HF Patients: Individual Patient-Data Meta-Analysis of RALES, EMPAHSIS-HF, and TOPCAT.

Ferreira JP, Rossello X, Eschalier R, McMurray JJV, ... Pitt B, Zannad F
Objectives
This study sought to assess the effect of MRA treatment (vs. placebo) in older patients (≥75 years of age) compared with younger patients (<75 years of age) with heart failure (HF).
Background
Mineralocorticoid receptor antagonists (MRAs) have been shown to reduce morbidity and mortality in patients with HF with reduced ejection fraction (HFrEF) and in a subset of patients with HF with preserved EF (HFpEF). Notwithstanding, MRAs are underused, especially in the elderly. Pooling the individual patient data (IPD) provided more statistical power with which to assess the efficacy and safety of MRA treatment in this subpopulation.
Methods
An IPD meta-analysis was performed using Cox proportional hazards models stratified by trial. A total of 1,756 patients (853 randomized to placebo and 903 to MRA) ≥75 years of age, along with 4,411 patients (2,242 randomized to placebo and 2,169 to MRA) <75 years of age were included. The primary outcome was a composite of death from cardiovascular causes or hospitalization for HF.
Results
The treatment groups were well balanced. Patients ≥75 years of age or older and those 80 years of age, 61% were male, 30% had diabetes, and the mean estimated glomerular filtration rate 59 ml/min. The primary outcome occurred in 331 patients (38.8%) in the placebo group versus 281 (31.1%) in the MRA group (hazard ratio: 0.74; 95% confidence interval: 0.63 to 0.86; p < 0.001; and the heterogeneity p value [heterogeneity p = Cochran\'s Q p value of treatment effect by study interaction] was 0.52). Cardiovascular death and all-cause death were also reduced by MRAs without significant between-trial or age (younger vs. older) heterogeneity. Worsening renal function and hyperkalemia occurred more frequently in patients taking MRAs (vs. placebo). Compared to younger patients, worsening renal function (but not hyperkalemia) was found more frequently in the elderly.
Conclusions
MRAs reduced morbidity and mortality in elderly patients with HF, a beneficial effect that is more marked in patients with HFrEF but homogenous across HFrEF and HFpEF. Implementation of measures that increase MRA treatment in this population are warranted.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Nov 2019; 7:1012-1021
Ferreira JP, Rossello X, Eschalier R, McMurray JJV, ... Pitt B, Zannad F
JACC Heart Fail: 29 Nov 2019; 7:1012-1021 | PMID: 31779922
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Lung Ultrasound in Acute Heart Failure: Prevalence of Pulmonary Congestion and Short- and Long-Term Outcomes.

Platz E, Campbell RT, Claggett B, Lewis EF, ... Solomon SD, McMurray JJV
Objectives
This study sought to assess the prevalence, changes in, and prognostic importance of B-lines, a pulmonary congestion measure by using a simplified lung ultrasonography (LUS) method in acute heart failure (AHF).
Background
Pulmonary congestion is an important finding in AHF, but conventional methods for its detection are insensitive.
Methods
In a 2-site, prospective, observational study, 4-zone LUS was performed early during hospitalization for AHF (LUS1) and at discharge (LUS2). B-lines were quantified off-line, blinded to clinical findings and outcomes, by a core laboratory.
Results
Among 349 patients (median, 75 years of age; 59% men; mean ejection fraction 39%), the sum of B-lines in 4 zones ranged from 0 to 18 (LUS1). The risk of an adverse in-hospital event increased with rising number of B-lines on LUS1: the odds ratio for each B-line tertile was 1.82 (95% confidence interval [CI]: 1.14 to 2.88; p = 0.011). B-line count decreased from a median of 6 (LUS1) to 4 (LUS2; p < 0.001) over 6 days (median). In 132 patients with LUS2 images, the risk of HF hospitalization or all-cause death was greater in patients with a higher number of B-lines at discharge. This relationship was stronger closer to discharge: unadjusted hazard ratio (HR) at 60 days was 3.30 (95% CI: 1.52 to 7.17; p = 0.002); 2.94 at 90 days (95% CI: 1.46 to 5.93; p = 0.003); and 2.01 at 180 days (95% CI: 1.11 to 3.64; p = 0.021). The association between number of B-lines and short- and long-term outcomes persisted after adjusting for important clinical variables, including N-terminal pro-B-type natriuretic peptide.
Conclusions
Pulmonary congestion using a simplified 4-zone LUS method was common in patients with AHF and improved with therapy. A higher number of B-lines at baseline and discharge identified patients at increased risk for adverse events.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Sep 2019; 7:849-858
Platz E, Campbell RT, Claggett B, Lewis EF, ... Solomon SD, McMurray JJV
JACC Heart Fail: 29 Sep 2019; 7:849-858 | PMID: 31582107
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Clinical Outcomes After Left Ventricular Assist Device Implantation in Older Adults: An INTERMACS Analysis.

Caraballo C, DeFilippis EM, Nakagawa S, Ravindra NG, ... Ahmad T, Topkara VK
Objectives
The purpose of this study was to examine outcomes after left ventricular assist device (LVAD) implantation in older adults (>75 years of age).
Background
An aging heart failure population together with improvements in mechanical circulatory support (MCS) technology have led to increasing LVAD implantations in older adults. However, data presenting age-specific outcomes are limited.
Methods
Adult patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) who required durable MCS between 2008 and 2017 were included. Patients were stratified by 4 age groups: <55 years of age, 55 to 64 years of age, and >75 years of age. Kaplan-Meier survival estimates were used to assess post-LVAD outcomes, with log-rank testing used to compare groups. Univariate and multivariate cox proportional hazard regression models were used to determine predictors of survival and complications.
Results
A total of 20,939 individuals received an LVAD during the study period: 7,743 (37.0%) were <55 years of age, 6,755 (32.3%) were 55 to 64 years of age, 5,418 (25.9%) were 65 to 74 years of age, and 1,023 (4.9%) were ≥75 years of age or older. After multivariate adjustment, adults ≥75 years of age had increased mortality post-LVAD implantation. Elderly patients with LVADs had a higher incidence of gastrointestinal bleeding but lower rates of device thrombosis. Compared to 84.5% of patients <55 years of age who were discharged home, only 46.8% of adults ≥75 years of age were discharged home following implantation (p < 0.001). Use of a RVAD, serum albumin level, and 6-min walk test distances were identified as predictors of outcomes in the oldest cohort.
Conclusions
Despite careful selection of older adults for LVAD implantation, age remains a significant predictor of mortality. Higher bleeding and lower clotting risk in elderly patients with LVADs support the use of a less intense antithrombotic regimen in this unique population.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Nov 2019; 7:1069-1078
Caraballo C, DeFilippis EM, Nakagawa S, Ravindra NG, ... Ahmad T, Topkara VK
JACC Heart Fail: 29 Nov 2019; 7:1069-1078 | PMID: 31779930
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Clinical Phenogroups in Heart Failure With Preserved Ejection Fraction: Detailed Phenotypes, Prognosis, and Response to Spironolactone.

Cohen JB, Schrauben SJ, Zhao L, Basso MD, ... Cappola T, Chirinos JA
Objectives
This study sought to assess if clinical phenogroups differ in comprehensive biomarker profiles, cardiac and arterial structure/function, and responses to spironolactone therapy.
Background
Previous studies identified distinct subgroups (phenogroups) of patients with heart failure with preserved ejection fraction (HFpEF).
Methods
Among Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) participants, we performed latent-class analysis to identify HFpEF phenogroups based on standard clinical features and assessed differences in multiple biomarkers measured from frozen plasma; cardiac and arterial structure/function measured with echocardiography and arterial tonometry; prognosis; and response to spironolactone.
Results
Three HFpEF phenogroups were identified. Phenogroup 1 (n = 1,214) exhibited younger age, higher prevalence of smoking, preserved functional class, and the least evidence of left ventricular (LV) hypertrophy and arterial stiffness. Phenogroup 2 (n = 1,329) was older, with normotrophic concentric LV remodeling, atrial fibrillation, left atrial enlargement, large-artery stiffening, and biomarkers of innate immunity and vascular calcification. Phenogroup 3 (n = 899) demonstrated more functional impairment, obesity, diabetes, chronic kidney disease, concentric LV hypertrophy, high renin, and biomarkers of tumor necrosis factor-alpha-mediated inflammation, liver fibrosis, and tissue remodeling. Compared with phenogroup 1, phenogroup 3 exhibited the highest risk of the primary endpoint of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest (hazard ratio [HR]: 3.44; 95% confidence interval [CI]: 2.79 to 4.24); phenogroups 2 and 3 demonstrated similar all-cause mortality (phenotype 2 HR: 2.36; 95% CI: 1.89 to 2.95; phenotype 3 HR: 2.26, 95% CI: 1.77 to 2.87). Spironolactone randomized therapy was associated with a more pronounced reduction in the risk of the primary endpoint in phenogroup 3 (HR: 0.75; 95% CI: 0.59 to 0.95; p for interaction = 0.016). Results were similar after excluding participants from Eastern Europe.
Conclusions
We identified important differences in circulating biomarkers, cardiac/arterial characteristics, prognosis, and response to spironolactone across clinical HFpEF phenogroups. These findings suggest distinct underlying mechanisms across clinically identifiable phenogroups of HFpEF that may benefit from different targeted interventions.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 07 Jan 2020; epub ahead of print
Cohen JB, Schrauben SJ, Zhao L, Basso MD, ... Cappola T, Chirinos JA
JACC Heart Fail: 07 Jan 2020; epub ahead of print | PMID: 31926856
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Advanced Heart Failure in Adults With Congenital Heart Disease.

Menachem JN, Schlendorf KH, Mazurek JA, Bichell DP, ... Book W, Lindenfeld J

As a result of improvements in care for patients with congenital heart disease (CHD), >90% of children born with CHD are expected to survive to adulthood. For those adults, heart failure (HF) is the leading cause of death. Advances in recognition of, and treatments for, these patients continue to improve. Specifically, adults with CHD are candidates for both heart transplantation and mechanical circulatory support. However, challenges remain that require investigation to improve outcomes.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 02 Dec 2019; epub ahead of print
Menachem JN, Schlendorf KH, Mazurek JA, Bichell DP, ... Book W, Lindenfeld J
JACC Heart Fail: 02 Dec 2019; epub ahead of print | PMID: 31838031
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The Hospital Readmissions Reduction Program: Nationwide Perspectives and Recommendations.

Psotka MA, Fonarow GC, Allen LA, Joynt Maddox KE, ... Yancy CW, O\'Connor CM

The mandatory federal pay-for-performance Hospital Readmissions Reduction Program (HRRP) was created to decrease 30-day hospital readmissions by instituting accountability and stimulating quality care and coordination, particularly during care transitions. The HRRP has changed the landscape of hospital readmissions and reimbursement within the United States by imposing substantial Medicare payment penalties on hospitals with higher-than-expected readmission rates. However, the HRRP has been controversial since its inception, particularly in the field of heart failure. Proponents argue that it has reduced national readmission rates, in part by raising awareness and investment in mechanisms to better assist patients during discharge and transitions; opponents contend that it unfairly penalizes hospitals for issues beyond their control, has unintended negative consequences due to incentivizing readmission over survival, that it encourages \"gaming\" the system, was not tested before implementation, and that it does not specify how hospitals can improve their performance. This paper incorporates the diverse, nuanced, and sometimes divergent interpretations presented during a multifaceted expert clinician discussion regarding the HRRP and heart failure; in cases in which consensus opinions were achieved, they are presented, including regarding potential new iterations of the HRRP for the future. Potential improvements include more comprehensive incorporation of outcomes into the HRRP measure and better risk adjustment to improve equality and fairness.

Copyright © 2019 American College of Cardiology Foundation. All rights reserved.

JACC Heart Fail: 04 Oct 2019; epub ahead of print
Psotka MA, Fonarow GC, Allen LA, Joynt Maddox KE, ... Yancy CW, O'Connor CM
JACC Heart Fail: 04 Oct 2019; epub ahead of print | PMID: 31606360
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Race and Sex Differences in Modifiable Risk Factors and Incident Heart Failure.

Kubicki DM, Xu M, Akwo EA, Dixon D, ... Lipworth L, Gupta DK
Objectives
The purpose of this study was to examine race- and sex-based variation in the associations between modifiable risk factors and incident heart failure (HF) among the SCCS (Southern Community Cohort Study) participants.
Background
Low-income individuals in the southeastern United States have high HF incidence rates, but relative contributions of risk factors to HF are understudied in this population.
Methods
We studied 27,078 black or white SCCS participants (mean age: 56 years, 69% black, 63% women) enrolled between 2002 and 2009, without prevalent HF, receiving Centers for Medicare and Medicaid Services. The presence of hypertension, diabetes mellitus, physical underactivity, high body mass index, smoking, high cholesterol, and poor diet was assessed at enrollment. Incident HF was ascertained using International Classification of Diseases-9th revision, codes 428.x in Centers for Medicare and Medicaid Services data through December 31, 2010. Individual risk and population attributable risk for HF for each risk factor were quantified using multivariable Cox models.
Results
During a median (25th, 75th percentile) 5.2 (3.1, 6.7) years, 4,341 (16%) participants developed HF. Hypertension and diabetes were associated with greatest HF risk, whereas hypertension contributed the greatest population attributable risk, 31.8% (95% confidence interval: 27.3 to 36.0). In black participants, only hypertension and diabetes associated with HF risk; in white participants, smoking and high body mass index also associated with HF risk. Physical underactivity was a risk factor only in white women.
Conclusions
In this high-risk, low-income cohort, contributions of risk factors to HF varied, particularly by race. To reduce the population burden of HF, interventions tailored for specific race and sex groups may be warranted.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Jan 2020; 8:122-130
Kubicki DM, Xu M, Akwo EA, Dixon D, ... Lipworth L, Gupta DK
JACC Heart Fail: 30 Jan 2020; 8:122-130 | PMID: 32000962
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Differential Regulation of ANP and BNP in Acute Decompensated Heart Failure: Deficiency of ANP.

Reginauld SH, Cannone V, Iyer S, Scott C, ... Sangaralingham SJ, Burnett JC
Objectives
This study investigated the differential regulation of circulating atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in patients with acute decompensated heart failure (ADHF) and tested the hypothesis that a relative deficiency of ANP exists in a subgroup of patients with ADHF.
Background
The endocrine heart releases the cardiac hormones ANP and BNP, which play a key role in cardiovascular (CV), renal, and metabolic homeostasis. In heart failure (HF), both plasma ANP and BNP are increased as a compensatory homeostatic response to myocardial overload.
Methods
ANP and BNP concentrations were measured in a small group of patients with ADHF (n = 112). To support this study\'s goal, a total of 129 healthy subjects were prospectively recruited to establish contemporary normal values for ANP and BNP. Plasma 3\',5\'cyclic guanosine monophosphate (cGMP), ejection fraction (EF), and body mass index (BMI) were measured in these subjects.
Results
In cases of ADHF, 74% of patients showed elevated ANP and BNP. Importantly, 26% of patients were characterized as having normal ANP (21% of this subgroup had normal ANP and elevated BNP). Cyclic GMP was lowest in the ADHF group with normal levels of ANP (p < 0.001), whereas BMI and EF were inversely related to ANP levels (p = 0.003).
Conclusions
Among a subgroup of patients hospitalized with ADHF, the presence of an ANP deficiency is consistent with a differential regulation of ANP and BNP and suggests the existence of a potentially compromised compensatory cardiac endocrine response. These findings have implications for the pathophysiology, diagnostics, and therapeutics of human HF.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Sep 2019; 7:891-898
Reginauld SH, Cannone V, Iyer S, Scott C, ... Sangaralingham SJ, Burnett JC
JACC Heart Fail: 29 Sep 2019; 7:891-898 | PMID: 31521687
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Implantable Device Measured Physical Activity With Hospitalization for Heart Failure.

Kelly JP, Ballew NG, Lin L, Hammill BG, ... Greiner MA, Atwater BD
Objectives
Evaluate the association of physical activity (PA) level and longitudinal PA trajectory with a composite heart failure hospitalization and mortality endpoint over a 5-year follow-up period following implantation.
Background
Low device measured PA early after implantation of an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) is associated with poor outcomes.
Methods
We linked daily PA data from the Boston Scientific ALTITUDE dataset of patients with ICD or CRT-D implantation to Medicare claims data. We used a joint model to investigate the association of the composite endpoint with 1) the time-varying point estimate of PA and 2) the time-varying trajectory/slope of PA during follow-up.
Results
Among 20,927 patients with median activity level 85 min/day, 14.1% and 49.6% experienced the composite endpoint at 1 and 5 years. Adjusted joint model results showed that there was a 1.13 (95% confidence interval: 1.12 to 1.13)-fold increase in the hazard of the composite endpoint for 75 min of daily PA relative to 85 min of PA; and a within-patient 10-min decrease in average daily PA over an 8-week period from 85 to 75 min was associated with a hazard ratio of 4.02 (95% confidence interval: 3.82 to 4.22) for the composite endpoint.
Conclusions
Patients with large decreases in PA have significantly higher risk of experiencing heart failure hospitalization or death. PA data from implantable devices may identify patients before clinical decompensation.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 03 Feb 2020; epub ahead of print
Kelly JP, Ballew NG, Lin L, Hammill BG, ... Greiner MA, Atwater BD
JACC Heart Fail: 03 Feb 2020; epub ahead of print | PMID: 32035894
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

CABG Improves Outcomes in Patients With Ischemic Cardiomyopathy: 10-Year Follow-Up of the STICH Trial.

Howlett JG, Stebbins A, Petrie MC, Jhund PS, ... Al-Khalidi HR,
Objectives
The authors investigated the impact of coronary artery bypass grafting (CABG) on first and recurrent hospitalization in this population.
Background
In the STICH (Surgical Treatment for Ischemic Heart Failure) trial, CABG reduced all-cause death and hospitalization in patients with and ischemic cardiomyopathy and left ventricular ejection fraction <35%.
Methods
A total of 1,212 patients were randomized (610 to CABG + optimal medical therapy [CABG] and 602 to optimal medical therapy alone [MED] alone) and followed for a median of 9.8 years. All-cause and cause-specific hospitalizations were analyzed as time-to-first-event and as recurrent event analysis.
Results
Of the 1,212 patients, 757 died (62.4%) and 732 (60.4%) were hospitalized at least once, for a total of 2,549 total all-cause hospitalizations. Most hospitalizations (66.2%) were for cardiovascular causes, of which approximately one-half (907 or 52.9%) were for heart failure. More than 70% of all hospitalizations (1,817 or 71.3%) were recurrent events. The CABG group experienced fewer all-cause hospitalizations in the time-to-first-event (349 CABG vs. 383 MED, adjusted hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.74 to 0.98; p = 0.03) and in recurrent event analyses (1,199 CABG vs. 1,350 MED, HR: 0.78, 95% CI: 0.65 to 0.94; p < 0.001). This was driven by fewer total cardiovascular (CV) hospitalizations (744 vs. 968; p < 0.001, adjusted HR: 0.66, 95% CI: 0.55 to 0.81; p = 0.001), the majority of which were due to HF (395 vs. 512; p < 0.001, adjusted HR: 0.68, 95% CI: 0.52-0.89; p = 0.005). We did not observe a difference in non-CV events.
Conclusions
CABG reduces all-cause, CV, and HF hospitalizations in time-to-first-event and recurrent event analyses. (Comparison of Surgical and Medical Treatment for Congestive Heart Failure and Coronary Artery Disease [STICH]; NCT00023595).

Copyright © 2019 American College of Cardiology Foundation. All rights reserved.

JACC Heart Fail: 29 Sep 2019; 7:878-887
Howlett JG, Stebbins A, Petrie MC, Jhund PS, ... Al-Khalidi HR,
JACC Heart Fail: 29 Sep 2019; 7:878-887 | PMID: 31521682
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Heart Failure and the Affordable Care Act: Past, Present, and Future.

Wolfe JD, Joynt Maddox KE

The Affordable Care Act (ACA) and other major health care legislative acts have had an important impact on the care of heart failure patients in the United States. The main effects of the ACA include regulation of the health insurance industry, expansion of access to health care, and health care delivery system reform, which included the creation of several alternative payment models. Particular components of the ACA, such as the elimination of annual and lifetime caps on spending, Medicaid expansion, and the individual and employer mandate, could have positive effects for heart failure patients. However, the benefits of value-based and alternative payment models such as the Hospital Readmissions Reduction Program and bundled payment programs for heart failure outcomes are less clear, and controversy exists regarding whether some of these programs may even worsen outcomes. As the population ages and the prevalence of heart failure continues to rise, this syndrome will likely remain a key clinical focus for policymakers. Therefore, heart failure clinicians should be aware of how legislation affects clinical practice and be prepared to adapt to continued changes in health policy.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Aug 2019; 7:737-745
Wolfe JD, Joynt Maddox KE
JACC Heart Fail: 30 Aug 2019; 7:737-745 | PMID: 31401094
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Health-Related Quality of Life in Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial.

Chandra A, Vaduganathan M, Lewis EF, Claggett BL, ... Solomon SD,
Objectives
This study sought to describe baseline health-related quality of life (HRQL) in the PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF) trial, the largest heart failure with preserved ejection fraction (HFpEF) trial to date.
Background
There are limited data characterizing HRQL in patients with HFpEF using validated metrics.
Methods
The PARAGON-HF trial randomized symptomatic patients with HFpEF (≥45%) ≥50 years of age to either sacubitril/valsartan or valsartan. The study reports comprehensive baseline HRQL using Kansas City Cardiomyopathy Questionnaire (KCCQ) administered at randomization after active run-in period. The study then compares baseline HRQL with patients with heart failure with reduced ejection fraction (HFrEF) (≤40%) enrolled in the PARADIGM-HF (Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial. Forward multivariable stepwise regression modeling was performed separately in both trials to identify independent clinical correlates of KCCQ-Overall Summary (KCCQ-OS) score. PARADIGM-HF trial patients <50 years of age were excluded to enable comparison.
Results
In the PARAGON-HF trial, 4,735 of 4,822 patients (mean age 73 ± 8 years; 48% men) completed baseline KCCQ at randomization. Mean KCCQ-OS score was 71. Women had worse mean KCCQ-OS score than men did. Patients in the PARAGON-HF trial reported lower KCCQ scores in nearly all domains when compared with the PARADIGM-HF trial (KCCQ-OS score 71 ± 19 vs. 73 ± 19; p < 0.001). The strongest independent clinical correlates of adverse HRQL in both the PARAGON-HF and PARADIGM-HF trials were New York Heart Association functional class, female gender, lower extremity edema, body mass index, angina, dyspnea, and paroxysmal nocturnal dyspnea. After accounting for these clinical correlates of adverse HRQL that were common to both HFpEF and HFrEF patients, KCCQ-OS score did not differ significantly.
Conclusions
HRQL was largely worse in women and was similar in HFpEF and HFrEF after accounting for variation in demographics, functional status, and symptom burden. (Prospective Comparison of ARNI with ARB Global Outcomes in HFpEF [PARAGON-HF] NCT01920711; Prospective Comparison of ARNI with an ACE-Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255).

Copyright © 2019. Published by Elsevier Inc.

JACC Heart Fail: 29 Sep 2019; 7:862-874
Chandra A, Vaduganathan M, Lewis EF, Claggett BL, ... Solomon SD,
JACC Heart Fail: 29 Sep 2019; 7:862-874 | PMID: 31302043
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The Risk for Sudden Cardiac Death Among Patients Living With Heart Failure and Human Immunodeficiency Virus.

Alvi RM, Neilan AM, Tariq N, Hassan MO, ... Zanni MV, Neilan TG
Objectives
The aim of this study was to determine the incidence of sudden cardiac death (SCD) among persons living with human immunodeficiency virus infection (PHIV) with heart failure (HF), who were hospitalized for HF, and the risk factors associated with it.
Background
HF is associated with an increased risk for SCD. PHIV are at heightened risk for HF.
Methods
This was a retrospective study of 2,578 patients hospitalized with HF from a single academic center, of whom 344 were PHIV. The outcome of interest was SCD. Subgroup analyses were performed by strata of viral load (VL) and left ventricular ejection fraction (LVEF) <35%, 35% to 49%, and ≥50%.
Results
Of 2,578 patients with HF, 2,149 (86%) did not have implantable cardioverter-defibrillators; of these, there were 344 PHIV and 1,805 uninfected control subjects. Among PHIV with HF, 313 (91%) were prescribed antiretroviral therapy and 64% were virally suppressed. There were 191 SCDs over a median follow-up period of 19 months. Compared with control subjects, PHIV had a 3-fold increase in SCD (21.0% vs. 6.4%; adjusted odds ratio: 3.0; 95% confidence interval: 1.78 to 4.24). Among PHIV, cocaine use, lower LVEF, absence of beta-blocker prescription, and VL were predictors of SCD. The SCD rate among PHIV with undetectable VL was similar to the rate among uninfected subjects. Similar findings were observed by LVEF strata. Among PHIV with HF without conventional indications for an implantable cardioverter-defibrillator, the rate of SCD was 10% per year.
Conclusions
PHIV hospitalized with HF are at a markedly increased risk for SCD. SCD risk was increased in patients with lower LVEFs, lower CD4 counts, and higher VL.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Aug 2019; 7:759-767
Alvi RM, Neilan AM, Tariq N, Hassan MO, ... Zanni MV, Neilan TG
JACC Heart Fail: 30 Aug 2019; 7:759-767 | PMID: 31401096
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Ambulatory Advanced Heart Failure in Women: A Report From the REVIVAL Registry.

Stewart GC, Cascino T, Richards B, Khalatbari S, ... Aaronson KD,
Objectives
This study sought to explore clinical characteristics and outcomes in women and men with ambulatory advanced heart failure (HF).
Background
Women have been underrepresented in studies of advanced HF and have an increased mortality on the transplant waiting list and early after mechanical circulatory support (MCS). An increased understanding of the differential burden of HF between women and men is required to inform the use of mechanical circulatory support in ambulatory advanced HF patients.
Methods
REVIVAL (Registry Evaluation for Vital Information on Ventricular Assist Devices in Ambulatory Life) is a prospective, observational study of 400 outpatients with chronic systolic HF, New York Heart Association functional class II to IV, and 1 additional high-risk feature. Clinical characteristics, quality of life, and functional capacity were compared between women and men, as was a primary composite endpoint of death, durable MCS, or urgent heart transplantation at 1 year.
Results
REVIVAL enrolled 99 women (25% of the cohort) who had similar age, ejection fraction, INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profiles, medication use, and willingness to consider MCS as the men enrolled; however, women reported significantly greater limitations in quality of life with respect to physical limitation, reduced 6-min walk distance, and more frequent symptoms of depression. Nevertheless, 1-year combined risk of death, durable MCS, or urgent transplantation did not differ between women and men (24% vs. 22%; p = 0.94).
Conclusions
This study represents the largest report to date of women with ambulatory advanced HF receiving contemporary therapies. Systematic elicitation of patient-reported outcome measures uncovered an added burden of HF in women and may be an appropriate target of augmented support and intervention.

Copyright © 2019 American College of Cardiology Foundation. All rights reserved.

JACC Heart Fail: 29 Jun 2019; 7:602-611
Stewart GC, Cascino T, Richards B, Khalatbari S, ... Aaronson KD,
JACC Heart Fail: 29 Jun 2019; 7:602-611 | PMID: 31078480
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Frailty Among Older Decompensated Heart Failure Patients: Prevalence, Association With Patient-Centered Outcomes, and Efficient Detection Methods.

Pandey A, Kitzman D, Whellan DJ, Duncan PW, ... Chen H, Reeves GR
Objectives
This study sought to assess the prevalence of frailty, its associations with physical function, quality of life (QoL), cognition, and depression and to investigate more efficient methods of detection in older patients hospitalized with acute decompensated heart failure (ADHF).
Background
In contrast to the outpatient population with chronic HF, much less is known regarding frailty in older, hospitalized patients with ADHF.
Methods
Older hospitalized patients (N = 202) with ADHF underwent assessment of frailty (using Fried criteria), short physical performance battery (SPPB), 6-min walk test (6-MWT) distance, quality of life (QoL using the Kansas City Cardiomyopathy Questionnaire), cognition (using the Montreal Cognition Assessment), and depression (using the Geriatric Depression Screen [GDS]). The associations of frailty with these patient-centered outcomes were assessed by using adjusted linear regression models. Novel strategies to identify frailty were examined.
Results
A total of 50% of older, hospitalized patients with ADHF were frail, 48% were pre-frail, and 2% were non-frail. Female sex, burden of comorbidity, and prior HF hospitalization were significantly associated with higher likelihood of frailty. Frailty (vs. pre-frail status) was associated with a significantly worse SPPB score (5 ± 2.2 vs. 7 ± 2.4, respectively), 6-MWT distance (143 ± 79 m vs. 221 ± 99 m, respectively), QoL (35 ± 19 vs. 46 ± 21, respectively), and more depression (GDS score: 5.5 ± 3.5 vs. 4.2 ± 3.3, respectively) but similar cognition. These associations were unchanged after adjustment for age, sex, race, total comorbidities, and body mass index. Slow gait speed plus low physical activity signaled frailty status as well (C-statistic = 0.85).
Conclusions
Ninety-eight percent of older, hospitalized patients with ADHF are frail or pre-frail. Frailty (vs. pre-frail status) is associated with worse physical function, QoL, comorbidity, and depression. The simple 4-m walk test combined with self-reported physical activity may quickly and efficiently identify frailty in older patients with ADHF.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Nov 2019; 7:1079-1088
Pandey A, Kitzman D, Whellan DJ, Duncan PW, ... Chen H, Reeves GR
JACC Heart Fail: 29 Nov 2019; 7:1079-1088 | PMID: 31779931
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Comparative Effectiveness of Sacubitril-Valsartan Versus ACE/ARB Therapy in Heart Failure With Reduced Ejection Fraction.

Tan NY, Sangaralingham LR, Sangaralingham SJ, Yao X, Shah ND, Dunlay SM
Objectives
This paper aims to compare the effectiveness of sacubitril-valsartan and angiotensin-converting enzyme inhibitor (ACE)/angiotensin receptor blocker (ARB) in systolic heart failure (HF).
Background
Sacubitril-valsartan reduced risks of death and hospitalization for HF versus enalapril in ambulatory patients with HF and reduced ejection fraction in the PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor with Angiotensin Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in HF) trial. However, the comparative effectiveness of sacubitril-valsartan and ACE/ARB in patients treated in routine clinical practice is unclear.
Methods
We identified patients with systolic HF in a U.S. administrative claims database treated with sacubitril-valsartan or ACE/ARB from July 1, 2015, to February 2, 2018. One-to-one propensity score matching was used to balance patients on 29 clinical variables. Cox models were used to compare outcomes between treatment groups.
Results
A total of 7,893 matched pairs were included; mean (SD) follow-up was 6.3 (5.4) months. Sacubitril-valsartan was associated with lower risks of all-cause mortality or all-cause hospitalization (hazard ratio [HR]: 0.86, 95% confidence interval (CI): 0.81 to 0.91; p < 0.001), all-cause mortality (HR: 0.80, 95% CI: 0.66 to 0.97; p = 0.027), and all-cause hospitalization (HR: 0.86, 95% CI: 0.80 to 0.91; p < 0.001), but not HF hospitalization (HR: 1.07, 95% CI: 0.96 to 1.19; p = 0.26). A lower risk of the primary outcome with sacubitril-valsartan was observed in white patients (HR: 0.83, 95% CI: 0.76 to 0.90) but not black patients (21% of population, HR: 1.00, 95% CI: 0.88 to 1.15; interaction p = 0.032). No statistically significant differences in treatment response by sex or age were observed.
Conclusions
Sacubitril-valsartan was associated with lower risks of death and hospitalization compared with ACE/ARB in a heterogeneous cohort of patients with systolic HF. However, our finding that outcomes with sacubitril-valsartan and ACE/ARBs were similar in black patients warrants further evaluation.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 02 Dec 2019; epub ahead of print
Tan NY, Sangaralingham LR, Sangaralingham SJ, Yao X, Shah ND, Dunlay SM
JACC Heart Fail: 02 Dec 2019; epub ahead of print | PMID: 31838035
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Carvedilol Among Patients With Heart Failure With a Cocaine-Use Disorder.

Banerji D, Alvi RM, Afshar M, Tariq N, ... Groarke JD, Neilan TG
Objectives
This study sought to assess the safety of carvedilol therapy among heart failure (HF) patients with a cocaine-use disorder (CUD).
Background
Although carvedilol therapy is recommended among certain patients with HF, the safety and efficacy of carvedilol among HF patients with a CUD is unknown.
Methods
This was a single-center study of hospitalized patients with HF. Cocaine use was self-reported or defined as having a positive urine toxicology. Patients were divided by carvedilol prescription. Subgroup analyses were performed by strata of ejection fraction (EF) ≤40%, 41% to 49%, or ≥50%. Major adverse cardiovascular events (MACE) were defined as cardiovascular mortality and 30-day HF readmission.
Results
From a cohort of 2,578 patients hospitalized with HF in 2011, 503 patients with a CUD were identified, among whom 404 (80%) were prescribed carvedilol, and 99 (20%) were not. Both groups had similar characteristics; however, those prescribed carvedilol had a lower LVEF, heart rate, and N-terminal pro-B-type natriuretic peptide concentrations at admission and on discharge, and more coronary artery disease. Over a median follow-up of 19 months, there were 169 MACEs. The MACE rates were similar between the carvedilol and the non-carvedilol groups (32% vs. 38%, respectively; p = 0.16) and between those with a preserved EF (30% vs. 33%, respectively; p = 0.48) and were lower in patients with a reduced EF taking carvedilol (34% vs. 58%, respectively; p = 0.02). In a multivariate model, carvedilol therapy was associated with lower MACE among patients with HF with a CUD (hazard ratio: 0.67; 95% confidence interval; 0.481 to 0.863).
Conclusions
Our findings suggest that carvedilol therapy is safe for patients with HF with a CUD and may be effective among those with a reduced EF.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Aug 2019; 7:771-778
Banerji D, Alvi RM, Afshar M, Tariq N, ... Groarke JD, Neilan TG
JACC Heart Fail: 30 Aug 2019; 7:771-778 | PMID: 31466673
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Mineralocorticoid Receptor Antagonists, Blood Pressure, and Outcomes in Heart Failure With Reduced Ejection Fraction.

Serenelli M, Jackson A, Dewan P, Jhund PS, ... Ferreira JP, McMurray JJV
Objectives
The purpose of this study was to investigate the effects of mineralocorticoid receptor antagonists (MRAs) on systolic blood pressure (SBP) and outcomes according to baseline SBP in patients with heart failure with reduced ejection fraction (HFrEF).
Background
MRAs are greatly underused in patients with HFrEF, often because of fear of adverse events. Concern about hypotension has been raised by the demonstration that MRAs are particularly effective treatment for resistant hypertension.
Methods
The effect of MRA therapy was studied in 4,396 patients with HFrEF randomized in the RALES (Randomized Aldactone Evaluation Study) and EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure) trials.
Results
Mean SBP change from baseline to 6 months was +1.4 ± 18.1 mm Hg in the placebo group and -1.2 ± 17.9 mm Hg in the MRA group. The between-treatment difference was 2.6 (95% confidence interval [CI]: 1.5 to 3.6; p < 0.001) mm Hg. All outcomes were reduced by MRA therapy overall, with consistent effects across SBP categories (e.g., all-cause mortality, overall hazard ratio [HR] of 0.72; 95% CI: 0.64 to 0.82; p < 0.001; SBP ≤105 mm Hg; HR: 0.72; 95% CI: 0.56 to 0.94; SBP >105 to ≤115 mm Hg; HR: 0.78; 95% CI: 0.60 to 1.02; SBP >115 to ≤125 mm Hg; HR: 0.71; 95% CI: 0.53 to 0.94; SBP >125 to ≤135 mm Hg; HR: 0.79; 95% CI: 0.57 to 1.10; and SBP > 135 mm Hg; HR: 0.67; 95% CI: 0.50 to 0.90; p for interaction = 0.95). Hypotension was infrequent and not more common with MRA therapy than with placebo, overall (4.6% vs. 3.9%; p = 0.25) or in any SBP category.
Conclusions
MRA treatment had little effect on SBP in patients with HFrEF, and the clinical benefits were not modified by baseline SBP. MRA treatment infrequently caused hypotension, even when the baseline SBP was low. The treatment discontinuation rates between MRA and placebo therapy were similar. Low SBP is not a reason to withhold MRA therapy in patients with HFrEF.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 05 Jan 2020; epub ahead of print
Serenelli M, Jackson A, Dewan P, Jhund PS, ... Ferreira JP, McMurray JJV
JACC Heart Fail: 05 Jan 2020; epub ahead of print | PMID: 31926854
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Socioeconomic Factors and Clinical Outcomes Among Patients With Heart Failure in a Universal Health Care System.

Schjødt I, Johnsen SP, Strömberg A, Kristensen NR, Løgstrup BB
Objectives
This study examined the associations between socioeconomic factors (SEF), readmission, and mortality in patients with incident heart failure (HF) with reduced ejection fraction (HFrEF) in a tax-financed universal health care system.
Background
Lack of health insurance is considered a key factor in health inequality, leading to poor clinical outcomes. However, data are sparse for the association between SEF and clinical outcomes among patients with HF in countries with tax-financed health care systems.
Methods
A nationwide population-based cohort study of 17,122 patients with incident HFrEF was carried out. Associations were assessed between individual-level SEF (cohabitation status, education, and income) and all-cause, HF, and non-HF readmission and mortality within 1 to 30, 31 to 90, and 91 to 365 days, as well as hospital bed days within 1 year after HF diagnosis.
Results
Low income was associated with a higher risk of all-cause readmission (adjusted hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.08 to 1.43) and non-HF readmission (HR: 1.36; 95% CI: 1.17 to 1.58) within days 31 to 90 as well as with a higher risk of all-cause (HR: 1.27; 95% CI: 1.14 to 1.41), HF (HR: 1.26; 95% CI: 1.02 to 1.55) and non-HF readmission (HR: 1.25; 95% CI: 1.12 to 1.39) within days 91 to 365. Low-income patients also had a higher use of hospital bed days and risk of mortality during follow-up.
Conclusions
In a tax-financed universal health care system, low income was associated with a higher risk of all-cause and non-HF readmission within 1 to 12 months after HF diagnosis and with HF readmission within 3 to 12 months among patients with incident HFrEF. Low-income patients also had a higher number of hospital bed days and a higher rate of mortality during follow-up.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Aug 2019; 7:746-755
Schjødt I, Johnsen SP, Strömberg A, Kristensen NR, Løgstrup BB
JACC Heart Fail: 30 Aug 2019; 7:746-755 | PMID: 31466671
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

CORT-AHF Study: Effect on Outcomes of Systemic Corticosteroid Therapy During Early Management Acute Heart Failure.

Miró Ò, Takagi K, Gayat E, Llorens P, ... Mueller C, Mebazaa A
Objectives
This study investigated whether systemic corticosteroids (new onset) administered to patients with acute heart failure (AHF) have any association with outcomes, with differentiated analyses for patients with and without chronic obstructive pulmonary disease (COPD) as a comorbidity.
Background
Patients with undiagnosed dyspnea frequently receive corticosteroids in emergency departments while determining a final diagnosis, but their effect on the outcomes of patients with AHF without overt COPD exacerbation is unknown.
Methods
We selected patients with AHF from the EAHFE (Epidemiology of Acute Heart Failure in the Emergency Departments) registry, recording key data (new-onset corticosteroid therapy, COPD condition). Patients with and without COPD were analyzed separately. We calculated unadjusted and adjusted ratios for corticosteroid-treated compared with corticosteroid-untreated patients for 2 coprimary endpoints: 90-day all-cause mortality (from index episode) and 90-day post-discharge combined endpoint (all-cause mortality or readmission for AHF), with intermediate time-point estimations. Other secondary endpoints were calculated, and some sensitive and stratified analyses were performed.
Results
We analyzed 11,356 patients: 8,635 without COPD (841 corticosteroid-treated, 9.7%) and 2,721 with COPD (753 corticosteroid-treated, 27.7%). There were several differences between treated and untreated patients, essentially because corticosteroid-treated patients were sicker. Although unadjusted outcomes were worse in corticosteroid-treated patients, especially in patients without COPD, these differences disappeared after adjustment: hazard ratios for 90-day mortality (without/with COPD) were 0.91 (95% confidence interval (CI): 0.76 to 1.10)/0.99 (95% CI: 0.78 to 1.26), and 1.09 (95% CI: 0.93 to 1.28)/1.02 (95% CI: 0.86 to 1.21) for the post-discharge combined endpoint. Analyses of intermediate time-point coprimary endpoints and secondary outcomes rendered similar estimations. Sensitivity and stratified analysis did not significantly modify these results.
Conclusions
There is no evidence of harm related to the new onset of systemic corticosteroid therapy during an episode of AHF, either in patients with or without concomitant COPD.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Sep 2019; 7:834-845
Miró Ò, Takagi K, Gayat E, Llorens P, ... Mueller C, Mebazaa A
JACC Heart Fail: 29 Sep 2019; 7:834-845 | PMID: 31521676
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Decline in Left Ventricular Ejection Fraction Following Anthracyclines Predicts Trastuzumab Cardiotoxicity.

Goel S, Liu J, Guo H, Barry W, ... Kohonen-Corish M, Beith J
Objectives
The aim of CATS (Cardiotoxicity of Adjuvant Trastuzumab Study) was to prospectively assess clinical, biochemical, and genomic predictors of trastuzumab-related cardiotoxicity (TRC).
Background
Cardiac dysfunction is a common adverse effect of trastuzumab. Studies to identify predictive biomarkers for TRC have enrolled heterogeneous populations and yielded mixed results.
Methods
A total of 222 patients with early-stage human epidermal growth factor receptor 2-positive breast cancer scheduled to receive adjuvant anthracyclines followed by 12 months of trastuzumab were prospectively recruited from 17 centers. Left ventricular ejection fraction (LVEF), troponin T, and N-terminal prohormone of brain natriuretic peptide were measured at baseline, post-anthracycline, and every 3 months during trastuzumab. Germline single-nucleotide polymorphisms in ERBB2, FCGR2A, and FCGR3A were analyzed. TRC was defined as symptomatic heart failure; cardiac death, arrhythmia, or infarction; a decrease in LVEF of >15% from baseline; or a decrease in LVEF of >10% to <50%.
Results
TRC occurred in 18 of 217 subjects (8.3%). Lower pre-anthracycline LVEF and greater interval decline in LVEF from pre- to post-anthracycline were each associated with TRC on multivariate analyses (odds ratio: 3.9 [p = 0.0001] and 7.9 [p < 0.0001] for a 5% absolute change in LVEF). Higher post-anthracycline N-terminal prohormone of brain natriuretic peptide level was associated with TRC on univariate but not multivariate analyses. There were no associations between troponin T or ERBB2/FGCR polymorphisms and TRC. Baseline LVEF and LVEF change post-anthracycline were used to generate a \"low-risk TRC score\" to identify patients with low TRC incidence.
Conclusions
Low baseline LVEF and greater LVEF decline post-anthracycline were both independent predictors of TRC. The other biomarkers did not further improve the ability to predict TRC. (Cardiotoxicity of Adjuvant Trastuzumab [CATS]; NCT00858039).

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Aug 2019; 7:795-804
Goel S, Liu J, Guo H, Barry W, ... Kohonen-Corish M, Beith J
JACC Heart Fail: 30 Aug 2019; 7:795-804 | PMID: 31401102
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of Age on Comorbidities and Outcomes in Heart Failure With Reduced Ejection Fraction.

Regan JA, Kitzman DW, Leifer ES, Kraus WE, ... O\'Connor CM, Mentz RJ
Objectives
This study sought to determine whether age modifies the impact of key comorbidities on clinical outcomes for patients with heart failure with reduced ejection fraction (HFrEF).
Background
Comorbidities impact outcomes in HFrEF. However, the effect of age on the impact of comorbidities on prognosis is not clearly understood.
Methods
Cox proportional hazards models were used assessed interactions between age and comorbidities on the primary composite endpoint (all-cause mortality or hospitalization) and secondary endpoints in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) multicenter trial of 2,331 patients with HFrEF.
Results
Age did not significantly modify the effect of any comorbidity on the primary endpoint. However, age significantly modified the effect of body mass index (BMI) on all-cause mortality (interaction p = 0.02). Among patients ≥70 years of age, there was a U-shaped relationship between BMI and 1-year mortality, where BMI of 20 kg/m corresponded to 17.6%; a BMI of 30 kg/m corresponded to 7.0%; and a BMI of 40 kg/m corresponded to 11%. For patients <60 years of age, mortality increased nonsignificantly from 3.2% to 3.7% with increasing BMI. Age also modified the effect of depressive symptoms on all-cause mortality (interaction p = 0.03). Among patients ≥70 years of age, a 1-year mortality rate significantly increased from 7.8% for a Beck Depression Inventory (BDI) score of 5% to 15.6% for BDI of 20. For patients <60 years of age, mortality was nonsignificantly related to BDI. Cumulative comorbidity scores were stronger predictors than age for mortality/hospitalization.
Conclusions
In chronic HFrEF, age markedly altered the impact of BMI and depressive symptoms on all-cause mortality, with much higher risk in older patients, but was not as strong a predictor of mortality/hospitalizations as cumulative comorbidity score. (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training [HF-ACTION]; NCT00047437).

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Nov 2019; 7:1056-1065
Regan JA, Kitzman DW, Leifer ES, Kraus WE, ... O'Connor CM, Mentz RJ
JACC Heart Fail: 29 Nov 2019; 7:1056-1065 | PMID: 31779928
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Circulating Neprilysin in Patients With Heart Failure and Preserved Ejection Fraction.

Lyle MA, Iyer SR, Redfield MM, Reddy YNV, ... Burnett JC, Pereira NL
Background
In heart failure with reduced ejection fraction (HFrEF), elevated soluble neprilysin (sNEP) levels are associated with an increased risk of cardiovascular death, and its inhibition with sacubitril/valsartan has improved survival.
Objectives
This study sought to determine the relevance of sNEP as a biomarker in heart failure with preserved ejection fraction (HFpEF) and to compare circulating sNEP levels in HFpEF patients with normal controls.
Methods
A case-control study was performed in 242 symptomatic HFpEF patients previously enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) and Nitrates\'s Effect on Activity Tolerance in Heart Failure With Preserved Ejection (NEAT-HFpEF) clinical trials and 891 asymptomatic subjects without HF or diastolic dysfunction (confirmed by NT-proBNP levels <200 pg/ml and echocardiography) who were enrolled in the Prevalence of Asymptomatic Left Ventricular Dysfunction study. sNEP was measured using a sandwich enzyme-linked immunosorbent assay (ELISA) in all subjects.
Results
Overall, sNEP levels were lower in HFpEF compared with controls (3.5 ng/ml; confidence interval [CI]: 2.5 to 4.8 vs. 8.5 ng/ml; CI: 7.2 to 10.0; p < 0.001). After adjusting for age, gender, body mass index (BMI), and smoking history, mean sNEP levels were also lower in HFpEF compared with controls (4.0 ng/ml [CI: 2.7 to 5.4] vs. 8.2 ng/ml [CI: 6.8 to 9.7]; p = 0.002). The cohorts were propensity matched based on age, BMI, diabetes, hypertension, smoking history, and renal function, and sNEP levels remained lower in HFpEF compared with controls (median 2.4 ng/ml [interquartile range: 0.6 to 27.7] vs. 4.9 ng/ml [interquartile range: 1.2 to 42.2]; p = 0.02).
Conclusions
Patients with HFpEF on average have significantly lower circulating sNEP levels compared with controls. These findings challenge our current understanding of the complex biology of circulating sNEP in HFpEF.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 06 Aug 2019; epub ahead of print
Lyle MA, Iyer SR, Redfield MM, Reddy YNV, ... Burnett JC, Pereira NL
JACC Heart Fail: 06 Aug 2019; epub ahead of print | PMID: 31392960
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Diastolic Determinants of Excess Mortality in Heart Failure With Reduced Ejection Fraction.

Benfari G, Miller WL, Antoine C, Rossi A, ... Thapa P, Enriquez-Sarano M
Objectives
The objective of this study was to determine short- and long-term excess mortality associated with diastolic echocardiographic measures (primarily E/e\' ratio) in patients with HF with reduced ejection fraction.
Background
In patients with heart failure (HF), Doppler echocardiography diastolic alterations are frequently but not convincingly linked to survival. Consequently, they are not included in risk-score algorithms or substantially mentioned in HF guidelines.
Methods
Consecutive patients with HF Stage B to C, diagnosed between 2003 and 2011, with ejection fraction <50%, Doppler diastolic characterization, complete clinical evaluation, and estimated pulmonary pressure, were analyzed. Outcome measure was mortality under medical management.
Results
The 12,421 eligible patients were 69 ± 14 years of age, 32% were women, 72% had Stage C HF, with ejection fraction 36 ± 10% and E/e\' ratio of 17 ± 9. During median follow-up 4.0 (1.1 to 7.0) years, 1-year and 5-year mortality were 17 ± 0.4% and 42 ± 0.5%. E/e\' ratio >20 was linked to elevated 1-year mortality (adjusted odds ratio: 1.45 [95% confidence interval (CI): 1.16 to 1.83]; p = 0.001). Long-term E/e\' ratios >20 and >14 to 20 were associated with reduced survival (adjusted hazard ratio: 1.21 [95% CI: 1.07 to 1.37]; p = 0.003, and adjusted hazard ratio: 1.15 [95% CI: 1.02 to 1.29]; p = 0.02), independent of all HF characteristics and in all patients\' subsets, including HF Stage B and Stage C. Guideline-based diastolic-grade algorithm also independently predicted mortality (p < 0.0001) but was definable less frequently (70%).
Conclusions
In reduced ejection fraction HF, diastolic Doppler alterations entail considerable mortality independent of all presentation characteristics. Elevated E/e\' ratio, associated with worse HF at diagnosis, is also, independent of presentation, linked to substantial short-term reduced survival and long-term sustained excess mortality and should be incorporated into HF risk assessment.

Copyright © 2019. Published by Elsevier Inc.

JACC Heart Fail: 30 Aug 2019; 7:808-817
Benfari G, Miller WL, Antoine C, Rossi A, ... Thapa P, Enriquez-Sarano M
JACC Heart Fail: 30 Aug 2019; 7:808-817 | PMID: 31401099
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Imaging, Biomarker, and Clinical Predictors of Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction.

Aimo A, Gaggin HK, Barison A, Emdin M, Januzzi JL

In response to injury, hemodynamic changes, or neurohormonal activation, the heart undergoes a series of structural and functional changes that have been termed cardiac remodeling. Remodeling is defined as changes in cardiac geometry and/or function over time and can be measured in terms of changes in cardiac chamber dimensions, wall thickness, volumes, mass, and ejection fraction at serial imaging examinations. As to cardiac chambers, left ventricular (LV) remodeling has been best studied in patients with heart failure with reduced ejection fraction. Although LV remodeling may compensate for abnormal hemodynamic parameters and function in the short term, left unchecked, it is associated with worsening cardiac function and poor prognosis. On the other hand, reversing LV geometry and/or function closer to that of a normal heart (also known as reverse remodeling) is associated with improved cardiac function and better prognosis. Because of its close relationship with clinical outcomes, remodeling may potentially be targeted in clinical management and used in trials as a surrogate endpoint. Standardized definition of remodeling and reliable tools to predict and monitor the presence, direction, and magnitude of cardiac remodeling are needed. Together with clinical and imaging findings, circulating biomarkers (most notably N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin, and soluble suppression of tumorigenesis-2) may be helpful in this respect.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Aug 2019; 7:782-794
Aimo A, Gaggin HK, Barison A, Emdin M, Januzzi JL
JACC Heart Fail: 30 Aug 2019; 7:782-794 | PMID: 31401101
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Exercise-Based Rehabilitation for Heart Failure: Cochrane Systematic Review, Meta-Analysis, and Trial Sequential Analysis.

Taylor RS, Long L, Mordi IR, Madsen MT, ... Gluud C, Zwisler AD
Objectives
This study performed a contemporary systematic review and meta-analysis of exercise-based cardiac rehabilitation (ExCR) for heart failure (HF).
Background
There is an increasing call for trials of models of ExCR for patients with HF that provide alternatives to conventional center-based provision and recruitment of patients that reflect a broader HF population.
Methods
The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, and PsycINFO databases were searched between January 2013 and January 2018. Randomized trials comparing patients undergoing ExCR to control patients not undergoing exercise were included. Study outcomes were pooled using meta-analysis. Metaregression examined potential effect modification according to ExCR program characteristics, and risk of bias, trial sequential analysis (TSA), and Grading of Recommendations Assessment Development and Evaluation (GRADE) were applied.
Results
Across 44 trials (n = 5,783; median follow-up of 6 months), compared with control subjects, ExCR did not reduce the risk of all-cause mortality (relative risk [RR]: 0.89; 95% confidence interval [CI]: 0.66 to 1.21; TSA-adjusted CI: 0.26 to 3.10) but did reduce all-cause hospitalization (RR: 0.70; 95% CI: 0.60 to 0.83; TSA-adjusted CI: 0.54 to 0.92) and HF-specific hospitalization (RR: 0.59; 95% CI: 0.42 to 0.84; TSA-adjusted CI: 0.14 for 2.46), and patients reported improved Minnesota Living with Heart Failure questionnaire overall scores (mean difference: -7.1; 95% CI: -10.5 to -3.7; TSA-adjusted CI: -13.2 to -1.0). No evidence of differential effects across different models of delivery, including center- versus home-based programs, were found.
Conclusions
This review supports the beneficial effects of ExCR on patient outcomes. These benefits appear to be consistent across ExCR program characteristics. GRADE and TSA assessments indicated that further high-quality randomized trials are needed.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Jul 2019; 7:691-705
Taylor RS, Long L, Mordi IR, Madsen MT, ... Gluud C, Zwisler AD
JACC Heart Fail: 30 Jul 2019; 7:691-705 | PMID: 31302050
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Hemodynamic Effects of Weight Loss in Obesity: A Systematic Review and Meta-Analysis.

Reddy YNV, Anantha-Narayanan M, Obokata M, Koepp KE, ... Carter RE, Borlaug BA
Objectives
The authors aimed to explore whether weight loss may improve central hemodynamics in obesity.
Background
Hemodynamic abnormalities in obese heart failure with preserved ejection fraction patients are correlated with the amount of excess body mass, suggesting a possible causal relationship.
Methods
Relevant databases were systematically searched from inception to May 2018, without language restriction. Studies reporting invasive hemodynamic measures before and following therapeutic weight loss interventions in patients with obesity but no clinically overt heart failure were extracted.
Results
A total of 9 studies were identified, providing data for 110 patients. Six studies tested dietary intervention and 3 studies tested bariatric surgery. Over a median duration of 9.7 months (range 0.75 to 23.0 months), a median weight loss of 43 kg (range 10 to 58 kg) was associated with significant reductions in heart rate (-9 beats/min, 95% confidence interval [CI]: -12 to -6; p < 0.001), mean arterial pressure (-7 mm Hg, 95% CI: -11 to -3; p < 0.001), and resting oxygen consumption (-85 ml/min, 95% CI: -111 to -60; p < 0.001). Central cardiac hemodynamics improved, manifested by reductions in pulmonary capillary wedge pressure (-3 mm Hg, 95% CI: -5 to -1; p < 0.001) and mean pulmonary artery pressure (-5 mm Hg, 95% CI: -8 to -2; p = 0.001). Exercise hemodynamics were assessed in a subset of patients (n = 49) in which there was significant reduction in exercise pulmonary artery pressure (p = 0.02).
Conclusions
Therapeutic weight loss in obese patients without HF is associated with favorable hemodynamic effects. Randomized controlled trials evaluating strategies for weight loss in obese patients with heart failure such as the obese phenotype of heart failure with preserved ejection fraction are needed.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Jul 2019; 7:678-687
Reddy YNV, Anantha-Narayanan M, Obokata M, Koepp KE, ... Carter RE, Borlaug BA
JACC Heart Fail: 30 Jul 2019; 7:678-687 | PMID: 31302042
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Heart Failure Management Innovation Enabled by Electronic Health Records.

Kao DP, Trinkley KE, Lin CT

Patients with congestive heart failure (CHF) require complex medical management across the continuum of care. Electronic health records (EHR) are currently used for traditional tasks of documentation, reviewing and managing test results, computerized order entry, and billing. Unfortunately many clinicians view EHR as merely digitized versions of paper charts, which create additional work and cognitive burden without improving quality or efficiency of care. In fact, EHR are revolutionizing the care of chronic diseases such as CHF. This review describes how appropriate use of technologies offered by EHR can help standardize CHF care, promote adherence to evidence-based guidelines, optimize workflow efficiency, improve performance metrics, and facilitate patient engagement. This review discusses a number of tools including documentation templates, telehealth and telemedicine, health information exchange, order sets, clinical decision support, registries, and analytics. Where available, evidence of their potential utility in management of CHF is presented. Together these EHR tools can also be used to enhance quality improvement, patient management, and clinical research as part of a learning health care system model. This review describes how existing EHR tools can support patients, cardiologists, and care teams to deliver consistent, high-quality, coordinated, patient-centered, and guideline-concordant care of CHF.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 05 Jan 2020; epub ahead of print
Kao DP, Trinkley KE, Lin CT
JACC Heart Fail: 05 Jan 2020; epub ahead of print | PMID: 31926853
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Heart Failure Prevention in Older Patients Using Intensive Blood Pressure Reduction: Potential Role of Diuretics.

Upadhya B, Lovato LC, Rocco M, Lewis CE, ... Kitzman DW,
Objectives
This study assessed the potential role of differential diuretic drugs in preventing incident acute decompensated heart failure (ADHF) in the SPRINT (Systolic Blood Pressure Intervention Trial) study.
Background
SPRINT showed that intensive blood pressure reduction in older patients (50 to 97 years of age) resulted in 36% fewer incident cases of ADHF. However, some investigators have questioned whether this was due merely to intergroup differences in diuretic medications.
Methods
Detailed use of medication data prospectively collected throughout the trial were examined.
Results
ADHF events occurred in 173 of 9,361 participants. Diuretic medication increased in both arms from screening to baseline visit (from 45% to 50% in the standard arm; and from 43% to 63% in the intensive arm) and then remained steady. The lowest use of diuretic agents was among participants in the standard arm who never had an ADHF event. Withdrawal of diuretic agents at the baseline visit occurred in 6.1% (n = 284) of participants in the standard arm and 2.3% (n = 107) of participants in the intensive arm. Of these, only 11 developed ADHF during the trial (10 in the standard arm, 1 in the intensive arm), and only 1 occurred ≤1 month after diuretic withdrawal. The benefit of ADHF reduction remained significant even after excluding those 11 participants (hazard ratio [HR]: 0.69; 95% confidence interval [CI]: 0.5 to 0.94; p = 0.02). Most ADHF events occurred in participants who were taking prescribed diuretic therapy at the last visit, prior to the ADHF event. There was limited use of loop (<6%) and potassium-sparing diuretic agents (2%). Diuretic use was not a predictor of ADHF (HR: 0.96; 95% CI: 0.66 to 1.40; p = 0.83).
Conclusions
No evidence was found to suggest that the reduction in new ADHF events in SPRINT was due to differential diuretic use. (Systolic Blood Pressure Intervention Trial [SPRINT]; NCT01206062).

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Nov 2019; 7:1032-1041
Upadhya B, Lovato LC, Rocco M, Lewis CE, ... Kitzman DW,
JACC Heart Fail: 29 Nov 2019; 7:1032-1041 | PMID: 31779925
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Durability and Efficacy of Tricuspid Valve Repair in Patients Undergoing Left Ventricular Assist Device Implantation.

Barac YD, Nicoara A, Bishawi M, Schroder JN, ... Patel CB, Milano CA
Objectives
This study sought to determine the durability of tricuspid valve repair (TVr) performed concurrently with left ventricular assist device (LVAD) implantation and its association with the development of late right heart failure (RHF).
Background
Surgical management of tricuspid regurgitation (TR) at the time of LVAD implantation is performed in an attempt to reduce the occurrence of postoperative RHF. Limited data exist regarding the durability of TVr in patients with LVAD as well as its impact on development of late RHF.
Methods
A retrospective review was conducted of consecutive adult patients who underwent durable LVAD implantation and concurrent TVr at the authors\' institution between 2009 and 2017. Late RHF was defined as readmission for HF requiring inotropic or diuretic therapy. TVr failure was defined as moderate or severe TR at any follow-up echocardiographic examination after LVAD implantation.
Results
A total of 156 patients underwent LVAD and concurrent TVr during the study. Of the total, 59 patients (37.8%) had a failed TVr. The mean duration of echocardiographic follow-up was 23 ± 22 months. Of the 146 patients who were discharged after the index hospitalization, 53 patients (36.3%) developed late RHF. Multivariate Cox proportional hazard analysis demonstrated that TVr failure was an independent predictor of late RHF development (hazard ratio: 2.62; 95% confidence interval: 1.38 to 4.96; p = 0.003).
Conclusion
Failure of TVr in this cohort occurred at a significant rate. Failure of TVr is an independent risk factor for development of late RHF. Future studies should investigate strategies to reduce recurrence of significant TR.

Copyright © 2019 American College of Cardiology Foundation. All rights reserved.

JACC Heart Fail: 02 Dec 2019; epub ahead of print
Barac YD, Nicoara A, Bishawi M, Schroder JN, ... Patel CB, Milano CA
JACC Heart Fail: 02 Dec 2019; epub ahead of print | PMID: 31838034
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Predicting Risk for Incident Heart Failure With Omega-3 Fatty Acids: From MESA.

Block RC, Liu L, Herrington DM, Huang S, ... O\'Connell TD, Shearer GC
Objectives
The aim of this study was to determine if plasma eicosapentaenoic acid (EPA) abundance (%EPA) is associated with reduced hazard for primary heart failure (HF) events in the MESA (Multi-Ethnic Study of Atherosclerosis) trial.
Background
Clinical trials suggest that omega-3 polyunsaturated fatty acids (ω3 PUFAs) prevent sudden death in coronary heart disease and HF, but this is controversial. In mice, the authors demonstrated that the ω3 PUFA EPA prevents contractile dysfunction and fibrosis in an HF model, but whether this extends to humans is unclear.
Methods
In the MESA cohort, the authors tested if plasma phospholipid EPA predicts primary HF incidence, including HF with reduced ejection fraction (EF) (EF <45%) and HF with preserved EF (EF ≥45%) using Cox proportional hazards modeling.
Results
A total of 6,562 participants 45 to 84 years of age had EPA measured at baseline (1,794 black, 794 Chinese, 1,442 Hispanic, and 2,532 white; 52% women). Over a median follow-up period of 13.0 years, 292 HF events occurred: 128 HF with reduced EF, 110 HF with preserved EF, and 54 with unknown EF status. %EPA in HF-free participants was 0.76% (0.75% to 0.77%) but was lower in participants with HF at 0.69% (0.64% to 0.74%) (p = 0.005). Log %EPA was associated with lower HF incidence (hazard ratio: 0.73 [95% confidence interval: 0.60 to 0.91] per log-unit difference in %EPA; p = 0.001). Adjusting for age, sex, race, body mass index, smoking, diabetes mellitus, blood pressure, lipids and lipid-lowering drugs, albuminuria, and the lead fatty acid for each cluster did not change this relationship. Sensitivity analyses showed no dependence on HF type.
Conclusions
Higher plasma EPA was significantly associated with reduced risk for HF, with both reduced and preserved EF. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Jul 2019; 7:651-661
Block RC, Liu L, Herrington DM, Huang S, ... O'Connell TD, Shearer GC
JACC Heart Fail: 30 Jul 2019; 7:651-661 | PMID: 31302044
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Risk for Heart Failure: The Opportunity for Prevention With the American Heart Association\'s Life\'s Simple 7.

Uijl A, Koudstaal S, Vaartjes I, Boer JMA, ... Hoes AW, Sluijs I
Objectives
The aim of this study is to determine whether combinations of specific Life\'s Simple 7 (LS7) components are associated with reduced risk for heart failure (HF).
Background
The American Heart Association recommends the concept of LS7: healthy behaviors that have been shown to reduce cardiovascular disease.
Methods
A total of 37,803 participants from the EPIC-NL (European Prospective Investigation Into Cancer and Nutrition-Netherlands) cohort were included (mean age: 49.4 ± 11.9 years, 74.7% women). The LS7 score ranged from 0 to 14 and was calculated by assigning 0, 1, or 2 points for smoking, physical activity, body mass index, diet, blood pressure, total cholesterol, and blood glucose. An overall ideal score (11 to 14 points) was present in 23.2% of participants, an intermediate score (9 or 10 points) in 35.3%, and an inadequate score (0 to 8 points) in 41.5%.
Results
Over a median follow-up period of 15.2 years (interquartile range: 14.1 to 16.5 years), 690 participants (1.8%) developed HF. In Cox proportional hazards models, ideal and intermediate LS7 scores were associated with reduced risk for HF compared with the inadequate category (hazard ratio: 0.45 [95% confidence interval (CI): 0.34 to 0.60] and hazard ratio: 0.53 [95% CI: 0.44 to 0.64], respectively). Our analyses show that combinations with specific LS7 components, notably glucose, body mass index, smoking, and blood pressure, are associated with a lower incidence of HF.
Conclusions
A healthy lifestyle, as reflected in an ideal LS7 score, was associated with a 55% lower risk for HF compared with an inadequate LS7 score. Preventive strategies that target combinations of specific LS7 components could have a significant impact on decreasing incident HF in the population at large.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Jul 2019; 7:637-647
Uijl A, Koudstaal S, Vaartjes I, Boer JMA, ... Hoes AW, Sluijs I
JACC Heart Fail: 30 Jul 2019; 7:637-647 | PMID: 31302040
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Omecamtiv Mecarbil in Chronic Heart Failure With Reduced Ejection Fraction: Rationale and Design of GALACTIC-HF.

Teerlink JR, Diaz R, Felker GM, McMurray JJV, ... Malik FI, Honarpour N

A central factor in the pathogenesis of heart failure (HF) with reduced ejection fraction is the initial decrease in systolic function. Prior attempts at increasing cardiac contractility with oral drugs have uniformly resulted in signals of increased mortality at pharmacologically effective doses. Omecamtiv mecarbil is a novel, selective cardiac myosin activator that has been shown to improve cardiac function and to decrease ventricular volumes, heart rate, and N-terminal pro-B-type natriuretic peptide in patients with chronic HF. The GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) trial tests the hypotheses that omecamtiv mecarbil can safely improve symptoms, prevent clinical HF events, and delay CV death in patients with chronic HF. The GALACTIC-HF trial is an international, multicenter, randomized, double-blind, placebo-controlled, event-driven cardiovascular outcomes trial. More than 8,000 patients with chronic symptomatic (New York Heart Association functional class II to IV) HF, left ventricular ejection fraction ≤35%, elevated natriuretic peptides, and either current hospitalization for HF or history of hospitalization or emergency department visit for HF within a year of screening will be randomized to either oral placebo or omecamtiv mecarbil employing a pharmacokinetic-guided dose titration strategy using doses of 25, 37.5, or 50 mg twice daily. The primary efficacy outcome is the time to cardiovascular death or first HF event. The study has 90% power to assess a final hazard ratio of approximately 0.80 in cardiovascular death, the first secondary outcome. The GALACTIC-HF trial is the first trial examining whether selectively increasing cardiac contractility in patients with HF with reduced ejection fraction will result in improved clinical outcomes. (Registrational Study With Omecamtiv Mecarbil/AMG 423 to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329).

Published by Elsevier Inc.

JACC Heart Fail: 03 Feb 2020; epub ahead of print
Teerlink JR, Diaz R, Felker GM, McMurray JJV, ... Malik FI, Honarpour N
JACC Heart Fail: 03 Feb 2020; epub ahead of print | PMID: 32035892
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of Malnutrition Using Geriatric Nutritional Risk Index in Heart Failure With Preserved Ejection Fraction.

Minamisawa M, Seidelmann SB, Claggett B, Hegde SM, ... Pitt B, Solomon SD
Objectives
This study sought to investigate the relationship between malnutrition and adverse cardiovascular (CV) events in heart failure with preserved ejection fraction (HFpEF).
Background
Malnutrition is associated with poor prognosis in a wide range of illnesses, however, the prognostic impact of malnutrition in HFpEF patients is not well known.
Methods
Baseline malnutrition risk was determined in 1,677 patients with HFpEF enrolled in the Americas regions of the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial, according to 3 categories of the geriatric nutritional risk index (GNRI) as previously validated: moderate to severe, GNRI of <92; low, GNRI of 92 to <98; and absence of risk, GNRI of ≥98. The relationships between malnutrition risk and the primary composite outcome of CV events (CV death, heart failure hospitalization, or resuscitated sudden death) and all-cause death were examined.
Results
Approximately one-third of patients were at risk for malnutrition (moderate to severe: 11%; low: 25%; and absence of risk: 64%). Over a median of 2.9-years\' follow-up, compared to those with absent risk for malnutrition, moderate to severe risk was associated with significantly increased risk for the primary outcome, CV death and all-cause death (hazard ratio [HR]: 1.34; 95% confidence interval [CI]: 1.02 to 1.76; HR: 2.06; 95% CI: 1.40 to 3.03; and HR: 1.79; 95% CI: 1.33 to 2.42, respectively) after multivariate adjustment for age, sex, history of CV diseases, and laboratory biomarkers.
Conclusions
Patients with HFpEF are at an elevated risk for malnutrition, which was associated with an increased risk for CV events in this population.

Copyright © 2019 American College of Cardiology Foundation. All rights reserved.

JACC Heart Fail: 30 Jul 2019; 7:664-675
Minamisawa M, Seidelmann SB, Claggett B, Hegde SM, ... Pitt B, Solomon SD
JACC Heart Fail: 30 Jul 2019; 7:664-675 | PMID: 31302049
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Real World Use of Hypertonic Saline in Refractory Acute Decompensated Heart Failure: A U.S. Center\'s Experience.

Griffin M, Soufer A, Goljo E, Colna M, ... Wilson FP, Testani JM
Objectives
The purpose of this study was to investigate real world safety and efficacy of hypertonic saline therapy in cases of refractory acute decompensated heart failure (ADHF) at a large U.S. academic medical center.
Background
Hypertonic saline therapy has been described as a potential management strategy for refractory ADHF, but experience in the United States is limited.
Methods
A retrospective analysis was performed in all patients receiving hypertonic saline for diuretic therapy-resistant ADHF at the authors\' institution since March 2013. The primary analytic approach was a comparison of the trajectory of clinical variables prior to and after administration of hypertonic saline, with secondary focus on predictors of treatment response.
Results
A total of 58 hypertonic saline administration episodes were identified across 40 patients with diuretic-therapy refractory ADHF. Prior to hypertonic saline administration, serum sodium, chloride, and creatinine concentrations were worsening but improved after hypertonic saline administration (p < 0.001, all). Both total urine output and weight loss significantly improved with hypertonic saline (p = 0.01 and <0.001, respectively). Diuretic efficiency, defined as change in urine output per doubling of diuretic dose, also improved over this period (p < 0.01). There were no significant changes in respiratory status or overcorrection of serum sodium with the intervention.
Conclusions
In a cohort of patients who were refractory to ADHF, hypertonic saline administration was associated with increased diuretic efficiency, fluid and weight loss, and improvement of metabolic derangements, and no adverse respiratory or neurological signals were identified. Additional study of hypertonic saline as a diuretic adjuvant is warranted.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Jan 2020; epub ahead of print
Griffin M, Soufer A, Goljo E, Colna M, ... Wilson FP, Testani JM
JACC Heart Fail: 30 Jan 2020; epub ahead of print | PMID: 32035891
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Risk Models for Prediction of Implantable Cardioverter-Defibrillator Benefit: Insights From the DANISH Trial.

Kristensen SL, Levy WC, Shadman R, Nielsen JC, ... Køber L, Thune JJ
Objectives
This study aims to identify patients with nonischemic heart failure who are more likely to benefit from implantable cardioverter-defibrillator (ICD) implantation by use of established risk prediction models.
Background
It has been debated whether an ICD for primary prevention reduces mortality in patients with nonischemic heart failure.
Methods
The Seattle Heart Failure Model (SHFM) predicts all-cause mortality whereas the Seattle Proportional Risk Model (SPRM) predicts the proportion of sudden cardiac death (SCD) versus nonsudden death, with a higher score indicating a greater proportion of SCD. We report the effect of ICD implantation on all-cause mortality and SCD, according to median SPRM and SHFM scores in all 1,116 patients enrolled in the DANISH (Danish study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on mortality) trial.
Results
Among patients with an SPRM score above the median (n = 558), ICD implantation reduced all-cause mortality (hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.43 to 0.94), whereas patients with lower SPRM scores (n = 558) had no effect (HR: 1.08; 95% CI: 0.78 to 1.49, p for interaction = 0.04). The corresponding numbers for SHFM score above and below the median were HR: 0.84; 95% CI: 0.62 to 1.13 and HR: 0.82; 95% CI: 0.53 to 1.28, respectively (p for interaction = 0.980). In 177 patients with upper SPRM/upper SHFM, ICD implantation reduced all-cause mortality (HR: 0.45; 95% CI: 0.25 to 0.80) when compared to 381 patients with lower SPRM/upper SHFM (HR: 1.09; 95% CI: 0.76 to 1.55) (p for interaction <0.001).
Conclusions
Nonischemic heart failure patients with high predicted relative likelihood of SCD, as estimated by higher SPRM score, seemed to benefit from ICD implantation. (DANISH [Danish ICD Study in Patients With Ditaled Cardiomyopathy]; NCT00542945).

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Jul 2019; 7:717-724
Kristensen SL, Levy WC, Shadman R, Nielsen JC, ... Køber L, Thune JJ
JACC Heart Fail: 30 Jul 2019; 7:717-724 | PMID: 31302052
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Screening for Transthyretin Amyloid Cardiomyopathy in Everyday Practice.

Witteles RM, Bokhari S, Damy T, Elliott PM, ... Rapezzi C, Garcia-Pavia P

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a life-threatening, progressive, infiltrative disease caused by the deposition of transthyretin amyloid fibrils in the heart, and can often be overlooked as a common cause of heart failure. Delayed diagnosis due to lack of disease awareness and misdiagnosis results in a poorer prognosis. Early accurate diagnosis is therefore key to improving patient outcomes, particularly in the context of both the recent approval of tafamidis in some countries (including the United States) for the treatment of ATTR-CM, and of other promising therapies under development. With the availability of scintigraphy as an inexpensive, noninvasive diagnostic tool, the rationale to screen for ATTR-CM in high-risk populations of patients is increasingly warranted. Here the authors propose a framework of clinical scenarios in which screening for ATTR-CM is recommended, as well as diagnostic \"red flags\" that can assist in its diagnosis among the wider population of patients with heart failure.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Jul 2019; 7:709-716
Witteles RM, Bokhari S, Damy T, Elliott PM, ... Rapezzi C, Garcia-Pavia P
JACC Heart Fail: 30 Jul 2019; 7:709-716 | PMID: 31302046
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Burden and Causes of Hospital Admissions in Heart Failure During the Last Year of Life.

Madelaire C, Gustafsson F, Kristensen SL, D\'Souza M, ... Gislason G, Schou M
Objectives
This study aimed to evaluate the incidence and causes of hospitalization in the year preceding death of patients with heart failure (HF).
Background
Hospitalizations in HF are common, especially in the last period of the lives of patients with HF, but little is known about hospitalization burden and causes during this phase of the disease.
Methods
From Danish nationwide registries, we identified patients who died in the period 2001-2016 after having experienced HF for at least 1 year, and examined hospitalizations during the last year of life in age- and sex-stratified analyses.
Results
We included 32,157 patients. Median age at time of death was 81 years; 39% were women. A total of 26,561 (84%) patients were hospitalized at least once during the last year of life. The patients experienced a median of 2 (1 to 3) hospitalizations and spent 14 (3 to 31) days in the hospital. Of all hospitalizations (n = 80,362), 9,644 (12%) were due to HF, 14,738 (18%) due to other cardiovascular (CV) causes, and 51,696 (64%) due to non-CV causes (p < 0.001). The frequency of hospitalizations increased toward death, but the domination of non-CV causes remained consistent throughout the year, regardless of age and sex. If we included diagnoses covering renal insufficiency in the definition of HF hospitalizations, non-CV hospitalizations remained dominant (58%).
Conclusions
During the last year alive, patients with HF were more often hospitalized due to non-CV causes rather than HF. These findings warrant more focus on a multidisciplinary approach toward end-of-life care in patients with HF.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Jun 2019; 7:561-570
Madelaire C, Gustafsson F, Kristensen SL, D'Souza M, ... Gislason G, Schou M
JACC Heart Fail: 29 Jun 2019; 7:561-570 | PMID: 31248567
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Influence of Age on Efficacy and Safety of Spironolactone in Heart Failure.

Vardeny O, Claggett B, Vaduganathan M, Beldhuis I, ... Solomon SD,
Objectives
The authors examined efficacy and safety of spironolactone by age in the Americas region (N = 1,767) of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial.
Background
Heart failure with preserved ejection fraction disproportionately affects older adults who may exhibit changes in physiology and variable pharmacokinetics.
Methods
TOPCAT enrolled patients with heart failure and a left ventricular ejection fraction ≥45% who were age 50 or older with an estimated glomerular filtration rate ≥30 mL/min/1.73 m and prior heart failure hospitalization or elevated natriuretic peptide levels. Participants were randomized to spironolactone or placebo with a mean follow-up duration of 3.3 years. We assessed treatment effect and safety by protocol-defined age categories (<65, 65 to 74, and ≥75 years).
Results
The mean age was 72 ± 10 years (range 50 to 97 years) with 41% over the age of 75 years. Participants ≥75 years were more commonly women and white and had a lower body mass index and estimated glomerular filtration rate compared with the younger age categories. Spironolactone reduced the primary composite outcome compared with placebo across all age categories (p interaction = 0.42). However, spironolactone was associated with an increased risk of the safety endpoint (hazard ratio: 2.54; 95% confidence interval: 1.91 to 3.37; p < 0.001), particularly in older age groups (p interaction = 0.02). Findings in the whole TOPCAT cohort were consistent with results from the Americas region.
Conclusions
In this post hoc, exploratory analysis of the TOPCAT trial data from the Americas region, although there was no effect of age on efficacy, there were considerable effects of age on increased rates of adverse safety outcomes. These results should be weighed when considering spironolactone for older heart failure with preserved ejection fraction patients. (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist [TOPCAT]; NCT00094302).

Published by Elsevier Inc.

JACC Heart Fail: 29 Nov 2019; 7:1022-1028
Vardeny O, Claggett B, Vaduganathan M, Beldhuis I, ... Solomon SD,
JACC Heart Fail: 29 Nov 2019; 7:1022-1028 | PMID: 31779923
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Frailty Is Intertwined With Heart Failure: Mechanisms, Prevalence, Prognosis, Assessment, and Management.

Pandey A, Kitzman D, Reeves G

Frailty, a syndrome characterized by an exaggerated decline in function and reserve of multiple physiological systems, is common in older patients with heart failure (HF) and is associated with worse clinical and patient-reported outcomes. Although several detailed assessment tools have been developed and validated in the geriatric population, they are cumbersome, not validated in patients with HF, and not commonly used in routine management of patients with HF. More recently, there has been an increasing interest in developing simple frailty screening tools that could efficiently and quickly identify frail patients with HF in routine clinical settings. As the burden and recognition of frailty in older patients with HF increase, a more comprehensive approach to management is needed that targets deficits across multiple domains, including physical function and medical, cognitive, and social domains. Such a multidomain approach is critical to address the unique, multidimensional challenges to the care of these high-risk patients and to improve their functional status, quality of life, and long-term clinical outcomes. This review discusses the burden of frailty, the conceptual underpinnings of frailty in older patients with HF, and potential strategies for the assessment, screening, and management of frailty in this vulnerable patient population.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Nov 2019; 7:1001-1011
Pandey A, Kitzman D, Reeves G
JACC Heart Fail: 29 Nov 2019; 7:1001-1011 | PMID: 31779921
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

The Role of the Pericardium in Heart Failure: Implications for Pathophysiology and Treatment.

Borlaug BA, Reddy YNV

The elastic pericardium exerts a compressive contact force on the surface of the myocardium that becomes more substantial when heart volume increases, as in patients with various forms of heart failure (HF). Pericardial restraint plays an important role in determining hemodynamics and ventricular function in both health and disease. This review discusses the physiology of pericardial restraint in HF and explores the question of whether it can be targeted indirectly through medical interventions or directly through a number of existing and future therapies.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Jun 2019; 7:574-585
Borlaug BA, Reddy YNV
JACC Heart Fail: 29 Jun 2019; 7:574-585 | PMID: 31248569
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Hemodynamic Response to Exercise in Patients Supported by Continuous Flow Left Ventricular Assist Devices.

Moss N, Rakita V, Lala A, Parikh A, ... Burkhoff D, Mancini DM
Objectives
This study sought to characterize the hemodynamic response to exercise in LVAD-supported patients and identify parameters most strongly associated with peak oxygen consumption (VO).
Background
Despite improved survival for heart failure patients afforded by continuous flow left ventricular assist devices (LVADs), peak exercise capacity remains impaired. Mechanisms underlying this reduced functional capacity remain poorly understood.
Methods
Patients referred for post-VAD hemodynamic optimization from December 2017 through June 2019 were enrolled. Swan Ganz catheters were inserted and upright incremental bicycle ergometry with respiratory gas analysis was performed. Hemodynamic measurements, mixed venous saturation, and arterial blood pressure were recorded every 3 min during exercise. Linear correlations were performed between peak VO (ml/min) and peak Fick cardiac output (CO), peak device flow, the assumed intrinsic CO derived as Fick CO-device flow, peak pressure differential across the LVAD (mean arterial pressure-pulmonary capillary wedge pressure), peak pressure differential across right ventricle (mean pulmonary artery pressure - right atrial pressure) and systemic vascular resistance.
Results
Forty-five patients supported by axial flow pumps (n = 12) and centrifugal flow pumps (n = 33) were studied. There were 34 men and 11 women. Age averaged 60 ± 10 years. Peak VO averaged 10.6 ± 3.1 ml/kg/min. Fick CO had the greatest correlation with peak VO with r = 0.73 (p < 0.0001) followed by intrinsic CO (r = 0.67; p < 0.0001). Multivariate model that best predicted peak VO included Fick CO and peak arterial venous oxygen (AVO) difference.
Conclusions
LVAD supported patients have severely impaired peak exercise capacity. The peak Fick cardiac output was the best correlate of peak exercise performance.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 03 Feb 2020; epub ahead of print
Moss N, Rakita V, Lala A, Parikh A, ... Burkhoff D, Mancini DM
JACC Heart Fail: 03 Feb 2020; epub ahead of print | PMID: 32035893
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Bucindolol for the Maintenance of Sinus Rhythm in a Genotype-Defined HF Population: The GENETIC-AF Trial.

Piccini JP, Abraham WT, Dufton C, Carroll IA, ... Connolly SJ,
Objectives
The purpose of this study was to compare the effectiveness of bucindolol with that of metoprolol succinate for the maintenance of sinus rhythm in a genetically defined heart failure (HF) population with atrial fibrillation (AF).
Background
Bucindolol is a beta-blocker whose unique pharmacologic properties provide greater benefit in HF patients with reduced ejection fraction (HFrEF) who have the beta-adrenergic receptor (ADRB1) Arg389Arg genotype.
Methods
A total of 267 HFrEF patients with a left ventricular ejection fraction (LVEF) <0.50, symptomatic AF, and the ADRB1 Arg389Arg genotype were randomized 1:1 to receive bucindolol or metoprolol therapy and were up-titrated to target doses. The primary endpoint of AF or atrial flutter (AFL) or all-cause mortality (ACM) was evaluated by electrocardiogram (ECG) during a 24-week period.
Results
The hazard ratio (HR) for the primary endpoint was 1.01 (95% confidence interval [CI]: 0.71 to 1.42), but trends for bucindolol benefit were observed in several subgroups. Precision therapeutic phenotyping revealed that a differential response to bucindolol was associated with the interval of time from the initial diagnoses of AF and HF to randomization and with the onset of AF relative to that of the initial HF diagnosis. In a cohort whose first AF and HF diagnoses were <12 years prior to randomization, in which AF onset did not precede HF by more than 2 years (n = 196), the HR was 0.54 (95% CI: 0.33 to 0.87; p = 0.011).
Conclusions
Pharmacogenetically guided bucindolol therapy did not reduce the recurrence of AF/AFL or ACM compared to that of metoprolol therapy in HFrEF patients, but populations were identified who merited further investigation in future phase 3 trials.

Copyright © 2019. Published by Elsevier Inc.

JACC Heart Fail: 29 Jun 2019; 7:586-598
Piccini JP, Abraham WT, Dufton C, Carroll IA, ... Connolly SJ,
JACC Heart Fail: 29 Jun 2019; 7:586-598 | PMID: 31042551
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Factors Associated With Live Discharge of Heart Failure Patients From Hospice: A Multimethod Study.

Russell D, Baik D, Jordan L, Dooley F, ... Bowles KH, Creber RM
Objectives
This study identified sociodemographic and clinical factors that predicted live discharge among home hospice patients with heart failure, and related these findings to perspectives among health care providers about challenges to caring for these patients.
Background
Hospice patients with heart failure are frequently discharged from hospice before death (\"live discharge\"). However, little is known about the factors and circumstances associated with live discharge among patients with heart failure.
Methods
Quantitative analyses of patient medical records (N = 1,498) and qualitative interviews were performed with health care providers (n = 19) at a not-for-profit hospice agency in New York City.
Results
Thirty percent of home hospice patients with heart failure experienced a live discharge, most frequently due to 911 calls that led to acute hospitalization. The odds of acute hospitalization were higher for younger patients (age 18 to 74 years: adjusted odds ratio [AOR]: 2.10; 95% confidence interval [CI]: 1.34 to 3.28), African American (AOR: 2.06; 95% CI: 1.31 to 3.24) or Hispanic (AOR: 2.99; 95% CI: 1.99 to 4.50) patients, and higher functioning patients (Palliative Performance Scores of 50% to 70%; AOR: 5.68; 95% CI: 3.66 to 8.79). Qualitative interviews with health care providers highlighted the unique characteristics of heart failure (e.g., sudden changes in patients\' condition), the importance of patients\' understanding of hospice and their own prognosis, and the role of sociocultural and family context in precipitating and potentially preventing live discharge (e.g., absence of social supports in the home).
Conclusions
Live discharge from hospice, especially due to acute hospitalization, is common with heart failure. Greater attention is needed for patients\' knowledge of and readiness for hospice care, especially among younger and diverse populations, and for factors related to the social and family context in which hospice care is provided.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Jun 2019; 7:550-557
Russell D, Baik D, Jordan L, Dooley F, ... Bowles KH, Creber RM
JACC Heart Fail: 29 Jun 2019; 7:550-557 | PMID: 31078473
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Financial Incentives to Increase Cardiac Rehabilitation Participation Among Low-Socioeconomic Status Patients: A Randomized Clinical Trial.

Gaalema DE, Elliott RJ, Savage PD, Rengo JL, ... Higgins ST, Ades PA
Objectives
This study sought to examine the efficacy of financial incentives to increase Medicaid patient participation in and completion of cardiac rehabilitation (CR).
Background
Participation in CR reduces morbidity, mortality, and hospitalizations while improving quality of life. Lower-socioeconomic status (SES) patients are much less likely to attend and complete CR, despite being at increased risk for recurrent cardiovascular events.
Methods
A total of 130 individuals enrolled in Medicaid with a CR-qualifying cardiac event were randomized 1:1 to receive financial incentives on an escalating schedule ($4 to $50) for completing CR sessions or to receive usual care. Primary outcomes were CR participation (number of sessions completed) and completion (≥30 sessions completed). Secondary outcomes included changes in sociocognitive measurements (depressive/anxious symptoms, executive function), body composition (waist circumference, body mass index), fitness (peak VO) over 4 months, and combined number of hospitalizations and emergency department (ED) contacts over 1 year.
Results
Patients randomized to the incentive condition completed more sessions (22.4 vs. 14.7, respectively; p = 0.013) and were almost twice as likely to complete CR (55.4% vs. 29.2%, respectively; p = 0.002) as controls. Incentivized patients were also more likely to experience improvements in executive function (p < 0.001), although there were no significant effects on other secondary outcomes. Patients who completed ≥30 sessions had 47% fewer combined hospitalizations and ED visits (p = 0.014), as reflected by a nonsignificant trend by study condition with 39% fewer hospital contacts in the incentive condition group (p = 0.079).
Conclusions
Financial incentives improve CR participation among lower-SES patients following a cardiac event. Increasing participation among lower-SES patients in CR is critical for positive longer-term health outcomes. (Increasing Cardiac Rehabilitation Participation Among Medicaid Enrollees; NCT02172820).

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Jun 2019; 7:537-546
Gaalema DE, Elliott RJ, Savage PD, Rengo JL, ... Higgins ST, Ades PA
JACC Heart Fail: 29 Jun 2019; 7:537-546 | PMID: 31078475
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Changes in Heart Failure Treatment With Patients\' Health Status: Real-World Evidence From CHAMP-HF.

Thomas M, Khariton Y, Fonarow GC, Arnold SV, ... McCague K, Spertus JA
Objectives
The aim of this study was to use a multicenter, observational outpatient registry of patients with heart failure with reduced ejection fraction (HFrEF) to describe the association between changes in patients\' medications with changes in health status.
Background
Alleviating symptoms and improving function and quality of life for patients with HFrEF are primary treatment goals and potential indicators of quality. Whether titrating medications in routine clinical care improves patients\' health status is unknown.
Methods
The association of any change in HFrEF medications with 3-month change in health status, as measured using the 12-item Kansas City Cardiomyopathy Questionnaire Overall Summary Scale, was determined in unadjusted and multivariate-adjusted (25 clinical characteristics, baseline health status) models using hierarchical linear regression.
Results
Among 3,313 outpatients with HFrEF from 140 centers, 21.9% had medication changes. Three months later, 23.7% and 46.4% had clinically meaningfully worse (≥5-point decrease) and improved (≥5-point increase) Kansas City Cardiomyopathy Questionnaire Overall Summary Scale scores. The 3-month median change in Kansas City Cardiomyopathy Questionnaire Overall Summary Scale score for patients whose HFrEF medications were changed was significantly larger (7.3 points; interquartile range: -3.1 to 20.8 points) than in patients whose medications were not changed (3.1 points; interquartile range: -4.7 to 12.5 points) (adjusted difference 3.0 points; 95% confidence interval: 1.4 to 4.6 points; p < 0.001). Among patients whose medications were adjusted, 26% had very large clinical improvement (≥20 points) compared with 14% whose regimens were not changed.
Conclusions
In routine care of patients with HFrEF, changes in HFrEF medications were associated with significant improvements in patients\' health status, suggesting that health status-based performance measures can quantify the benefits of titrating medicines in patients with HFrEF.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Jun 2019; 7:615-625
Thomas M, Khariton Y, Fonarow GC, Arnold SV, ... McCague K, Spertus JA
JACC Heart Fail: 29 Jun 2019; 7:615-625 | PMID: 31176672
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cognitive Decline Over Time in Patients With Systolic Heart Failure: Insights From WARCEF.

Lee TC, Qian M, Liu Y, Graham S, ... Di Tullio MR,
Objectives
This study sought to characterize cognitive decline (CD) over time and its predictors in patients with systolic heart failure (HF).
Background
Despite the high prevalence of CD and its impact on mortality, predictors of CD in HF have not been established.
Methods
This study investigated CD in the WARCEF (Warfarin versus Aspirin in Reduced Ejection Fraction) trial, which performed yearly Mini-Mental State Examinations (MMSE) (higher scores indicate better cognitive function; e.g., normal score: 24 or higher). A longitudinal time-varying analysis was performed among pertinent covariates, including baseline MMSE and MMSE scores during follow-up, analyzed both as a continuous variable and a 2-point decrease. To account for a loss to follow-up, data at the baseline and at the 12-month visit were analyzed separately (sensitivity analysis).
Results
A total of 1,846 patients were included. In linear regression, MMSE decrease was independently associated with higher baseline MMSE score (p < 0.0001), older age (p < 0.0001), nonwhite race/ethnicity (p < 0.0001), and lower education (p < 0.0001). In logistic regression, CD was independently associated with higher baseline MMSE scores (odds ratio [OR]: 1.13; 95% confidence interval [CI]: 1.07 to 1.20]; p < 0.001), older age (OR: 1.37; 95% CI: 1.24 to 1.50; p < 0.001), nonwhite race/ethnicity (OR: 2.32; 95% CI: 1.72 to 3.13 for black; OR: 1.94; 95% CI: 1.40 to 2.69 for Hispanic vs. white; p < 0.001), lower education (p < 0.001), and New York Heart Association functional class II or higher (p = 0.03). Warfarin and other medications were not associated with CD. Similar trends were seen in the sensitivity analysis (n = 1,439).
Conclusions
CD in HF is predicted by baseline cognitive status, demographic variables, and NYHA functional class. The possibility of intervening on some of its predictors suggests the need for the frequent assessment of cognitive function in patients with HF. (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction [WARCEF]; NCT00041938).

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Nov 2019; 7:1042-1053
Lee TC, Qian M, Liu Y, Graham S, ... Di Tullio MR,
JACC Heart Fail: 29 Nov 2019; 7:1042-1053 | PMID: 31779926
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Distinct Pathological Pathways in Patients With Heart Failure and Diabetes.

Tromp J, Voors AA, Sharma A, Ferreira JP, ... Zannad F, Sama IE
Objectives
The aims of this study were to compare the characteristics of patients with and without diabetes and to use network analyses to compare biomarker profiles and associated pathways in patients with diabetes compared with those without diabetes, which might offer new avenues for potential therapeutic targets.
Background
Diabetes adversely affects clinical outcomes and complicates treatment in patients with heart failure (HF). A clear understanding of the pathophysiological processes associated with type 2 diabetes in HF is lacking.
Methods
Network and pathway over-representation analyses were performed to identify unique pathological pathways in patients with and without diabetes using 92 biomarkers from different pathophysiological domains measured in plasma samples from 1,572 patients with HF (31% with diabetes) with reduced ejection fraction (left ventricular ejection fraction <40%). The results were validated in an independent cohort of 729 patients (30% with diabetes).
Results
Biomarker profiles were first compared between patients with HF with and without diabetes. Patients with diabetes showed higher levels of galectin-4, growth differentiation factor 15, and fatty acid binding protein 4 and lower levels of paraoxonase 3. Network analyses were then performed, revealing that epidermal growth factor receptor and galectin-3 were the most prominent connecting proteins. Translation of these networks to biologic pathways revealed that diabetes was associated with inflammatory response and neutrophil degranulation. Diabetes conferred worse outcomes after correction for an established risk model (hazard ratio: 1.20; 95% confidence interval: 1.01 to 1.42).
Conclusions
Concomitant diabetes in patients with HF with reduced ejection fraction is associated with distinct pathophysiological pathways related to inflammation, protein phosphorylation, and neutrophil degranulation. These data support the evaluation of anti-inflammatory therapeutic approaches, epidermal growth factor receptor in particular, for patients with HF and diabetes.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Jan 2020; epub ahead of print
Tromp J, Voors AA, Sharma A, Ferreira JP, ... Zannad F, Sama IE
JACC Heart Fail: 30 Jan 2020; epub ahead of print | PMID: 32035890
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Association of Urine Albumin Excretion With Incident Heart Failure Hospitalization in Community-Dwelling Adults.

Bailey LN, Levitan EB, Judd SE, Sterling MR, ... Safford MM, Gutiérrez OM
Objectives
This study examined the association between urinary albumin excretion and incident heart failure (HF) hospitalization.
Background
Excess urinary albumin excretion is more strongly associated with incident stroke and coronary heart disease risk in black than in white individuals. Whether similar associations extend to HF is unclear.
Methods
This study examined the associations between the urinary albumin-to-creatinine ratio (ACR) and incident hospitalization for HF overall in 24,433 REGARDS (Reasons for Geographic and Racial Differences in Stroke) study participants free of suspected HF at baseline; findings were stratified by race and HF subtype (preserved vs. reduced ejection fraction). Models were adjusted for sociodemographic, clinical, and laboratory variables including estimated glomerular filtration rate, and multiple imputation was used to account for missing covariate data.
Results
After a median follow-up of 9.2 years, 881 incident HF events (332 preserved ejection fraction, 447 reduced ejection fraction, 102 unspecified) were observed. Compared to the lowest ACR category (<10 mg/g), the risk of incident HF increased with increasing ACR categories (10 to 29 mg/g hazard ratio [HR]: 1.49; 95% confidence interval [CI]: 1.26 to 1.78; 30 to 300 mg/g HR: 2.32; 95% CI: 1.93 to 2.78; >300 mg/g HR: 4.42; 95% CI: 3.36 to 5.83) in the fully adjusted model. Results did not differ by race. The magnitude of the association between ACR and HF with preserved ejection fraction was greater than with HF with reduced ejection fraction (HR comparing highest vs. lowest ACR category: 6.20; 95% CI: 4.15 to 9.26 vs. HR: 4.37; 95% CI: 3.00 to 6.25, respectively; p = 0.05).
Conclusions
Higher ACR was associated with greater risk of incident HF hospitalization in community-dwelling black and white adults.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Apr 2019; 7:394-401
Bailey LN, Levitan EB, Judd SE, Sterling MR, ... Safford MM, Gutiérrez OM
JACC Heart Fail: 29 Apr 2019; 7:394-401 | PMID: 31047019
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Sex-Based Differences in Heart Failure Across the Ejection Fraction Spectrum: Phenotyping, and Prognostic and Therapeutic Implications.

Stolfo D, Uijl A, Vedin O, Strömberg A, ... Dahlström U, Savarese G
Objectives
This study assessed sex-related differences in a large cohort of unselected patients with heart failure (HF) across the ejection fraction (EF) spectrum.
Background
Females are under-represented in randomized clinical trials. Potential sex-related differences in HF may question the generalizability of trials.
Methods
In the Swedish Heart Failure Registry population multivariate Cox and logistic regression models were fitted to investigate differences in prognosis, prognostic predictors, and treatments across males and females.
Results
Of 42,987 patients, 37% were females (55% with HF with preserved EF [HFpEF], 39% with HF with mid-range EF [HFmrEF], and 29% with HF with reduced EF [HFrEF]). Females were older and more symptomatic and more likely to have hypertension and kidney disease but less likely to have diabetes and ischemic heart disease. After adjustments, females were more likely to use beta-blockers and digoxin but less likely to receive HF device therapy. Crude mortality/HF hospitalization rates for HFpEF (hazard ratio [HR]: 1.16) and HFmrEF (HR: 1.14) were significantly higher in females but lower in females with HFrEF (HR: 0.95). After adjustments, the risk was significantly lower in females regardless of EF (HR: 0.80 in HFrEF, HR: 0.91 in HFmrEF, and HR: 0.93 in HFpEF). The main sex-related differences in prognostic predictors concerned diabetes in HFrEF and anemia in HFmrEF.
Conclusions
Males and females with HF showed different characteristics across the EF spectrum. Males reported a lower crude risk of mortality/morbidity in HFpEF and HFmrEF but higher risk of HFrEF, although after adjustments, prognosis was better in females regardless of EF. The observed sex-related differences highlight the need for an adequate representation of females in HF randomized controlled trials to improve generalizability.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 May 2019; 7:505-515
Stolfo D, Uijl A, Vedin O, Strömberg A, ... Dahlström U, Savarese G
JACC Heart Fail: 30 May 2019; 7:505-515 | PMID: 31146874
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Outcomes and Effect of Treatment According to Etiology in HFrEF: An Analysis of PARADIGM-HF.

Balmforth C, Simpson J, Shen L, Jhund PS, ... Packer M, McMurray JJV
Objectives
The purpose of this study was to compare outcomes (and the effect of sacubitril/valsartan) according to etiology in the PARADIGM-HF (Prospective comparison of angiotensin-receptor-neprilysin inhibitor [ARNI] with angiotensin-converting-enzyme inhibitor [ACEI] to Determine Impact on Global Mortality and morbidity in Heart Failure) trial.
Background
Etiology of heart failure (HF) has changed over time in more developed countries and is also evolving in non-Western societies. Outcomes may vary according to etiology, as may the effects of therapy.
Methods
We examined outcomes and the effect of sacubtril/valsartan according to investigator-reported etiology in PARADIGM-HF. The outcomes analyzed were the primary composite of cardiovascular death or HF hospitalization, and components, and death from any cause. Outcomes were adjusted for known prognostic variables including N terminal pro-B type natriuretic peptide.
Results
Among the 8,399 patients randomized, 5,036 patients (60.0%) had an ischemic etiology. Among the 3,363 patients (40.0%) with a nonischemic etiology, 1,595 (19.0% of all patients; 47% of nonischemic patients) had idiopathic dilated cardiomyopathy, 968 (11.5% of all patients; 28.8% of nonischemic patients) had a hypertensive cause, and 800 (9.5% of all patients, 23.8% of nonischemic patients) another cause (185 infective/viral, 158 alcoholic, 110 valvular, 66 diabetes, 30 drug-related, 14 peripartum-related, and 237 other). Whereas the unadjusted rates of all outcomes were highest in patients with an ischemic etiology, the adjusted hazard ratios (HRs) were not different from patients in the 2 major nonischemic etiology categories; for example, for the primary outcome, compared with ischemic (HR: 1.00), hypertensive 0.87 (95% confidence interval [CI]: 0.75 to 1.02), idiopathic 0.92 (95% CI: 0.82 to 1.04) and other 1.00 (95% CI: 0.85 to 1.17). The benefit of sacubitril/valsartan over enalapril was consistent across etiologic categories (interaction for primary outcome; p = 0.11).
Conclusions
Just under one-half of patients in this global trial had nonischemic HF with reduced ejection fraction, with idiopathic and hypertensive the most commonly ascribed etiologies. Adjusted outcomes were similar across etiologic categories, as was the benefit of sacubitril/valsartan over enalapril. (Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality of Patients With Chronic Heart Failure; NCT01035255).

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 May 2019; 7:457-465
Balmforth C, Simpson J, Shen L, Jhund PS, ... Packer M, McMurray JJV
JACC Heart Fail: 30 May 2019; 7:457-465 | PMID: 31078482
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Cardiogenic Shock in Takotsubo Cardiomyopathy Versus Acute Myocardial Infarction: An 8-Year National Perspective on Clinical Characteristics, Management, and Outcomes.

Vallabhajosyula S, Dunlay SM, Murphree DH, Barsness GW, ... Lerman A, Prasad A
Objectives
This study sought to evaluate the clinical characteristics and outcomes of Takotusbo cardiomyopathy cardiogenic shock (TC-CS) in comparison to those of acute myocardial infarction cardiogenic shock (AMI-CS) among patients hospitalized in the United States. We additionally sought to compare the incidence of multiorgan failure and use of supportive therapies as well as the trends over time, given the increasing awareness and diagnosis of TC.
Background
CS is a major complication of TC; however, there are limited data, especially as to how TC-CS compares to AMI-CS.
Methods
The National Inpatient Sample Database was used to identify adults hospitalized with CS in the setting of TC and AMI from 2007 to 2014. We required patients admitted with TC to have undergone coronary angiography without intervention. Clinical characteristics and in-hospital outcomes in TC-CS patients were compared with those in AMI-CS patients. Multivariate regression and propensity matching were used to adjust for potential confounding factors.
Results
Between 2007 and 2014, there were 374,152 admissions for CS due to either TC or AMI, of which 4,614 patients (1.2%) had TC-CS. TC-CS admission patients were more likely to be younger, white females with fewer comorbidities. Rates of respiratory failure and mechanical ventilation were higher in TC-CS, but cardiac arrest and acute kidney injury were lower. There were no differences between cohorts in use of intra-aortic balloon pumps. TC-CS admissions had lower in-hospital mortality (15% vs. 37%, respectively) and hospital costs (U.S. dollars: $135,397 ± $127,617 vs. $154,827 ± $186,035, respectively) and were discharged home more often (45% vs. 36%, respectively) compared to AMI-CS admissions (all: p < 0.001). After adjustments for potential confounders, TC-CS was associated with lower in-hospital mortality (odds ratio [OR]: 0.35; 95% confidence interval [CI]: 0.32 to 0.38; p < 0.001). Similar findings were observed in the propensity-matched cohort (OR: 0.32; 95% CI: 0.25 to 0.39; p < 0.001).
Conclusions
There are key differences between the clinical characteristics and multiorgan failure patterns in TC-CS compared to those in AMI-CS. In-hospital mortality (15%) is lower in TC-CS.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 May 2019; 7:469-476
Vallabhajosyula S, Dunlay SM, Murphree DH, Barsness GW, ... Lerman A, Prasad A
JACC Heart Fail: 30 May 2019; 7:469-476 | PMID: 31078481
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

International Consortium for Health Outcomes Measurement Standardized Outcome Measurement Set for Heart Failure Patients.

Burns DJP, Arora J, Okunade O, Beltrame JF, ... Stevenson LW, McDonagh TA

Whereas multiple national, international, and trial registries for heart failure have been created, international standards for clinical assessment and outcome measurement do not currently exist. The working group\'s objective was to facilitate international comparison in heart failure care, using standardized parameters and meaningful patient-centered outcomes for research and quality of care assessments. The International Consortium for Health Outcomes Measurement recruited an international working group of clinical heart failure experts, researchers, and patient representatives to define a standard set of outcomes and risk-adjustment variables. This was designed to document, compare, and ultimately improve patient care outcomes in the heart failure population, with a focus on global feasibility and relevance. The working group employed a Delphi process, patient focus groups, online patient surveys, and multiple systematic publications searches. The process occurred over 10 months, employing 7 international teleconferences. A 17-item set has been established, addressing selected functional, psychosocial, burden of care, and survival outcome domains. These measures were designed to include all patients with heart failure, whether entered at first presentation or subsequent decompensation, excluding cardiogenic shock. Sources include clinician report, administrative data, and validated patient-reported outcome measurement tools: the Kansas City Cardiomyopathy Questionnaire; the Patient Health Questionnaire-2; and the Patient-Reported Outcomes Measurement Information System. Recommended data included those to support risk adjustment and benchmarking across providers and regions. The International Consortium for Health Outcomes Measurement developed a dataset designed to capture, compare, and improve care for heart failure, with feasibility and relevance for patients and clinicians worldwide.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 02 Dec 2019; epub ahead of print
Burns DJP, Arora J, Okunade O, Beltrame JF, ... Stevenson LW, McDonagh TA
JACC Heart Fail: 02 Dec 2019; epub ahead of print | PMID: 31838032
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Heart Failure and Atrial Fibrillation, Like Fire and Fury.

Carlisle MA, Fudim M, DeVore AD, Piccini JP

Heart failure and atrial fibrillation are 2 common cardiovascular disorders that frequently complicate one another and exert a significant detrimental effect on cardiovascular health and well-being. Both heart failure and atrial fibrillation continue to increase in prevalence as the risk factors underlying each condition become more common. This review encompasses what is currently known about the epidemiology and pathophysiology of these comorbidities along with incorporation of landmark trials that have contributed to current guidelines. The focus is on clinically relevant considerations, including the contribution of inflammation in the pathophysiology of atrial fibrillation and heart failure. We explore the emerging role of catheter ablation relative to medical therapy in the management of heart failure with reduced ejection fraction, along with indications for biventricular pacing modalities in cardiac resynchronization therapy. We discuss current guideline-directed therapies and how practice models and national recommendations will likely change based on the most recent randomized controlled trials.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 May 2019; 7:447-456
Carlisle MA, Fudim M, DeVore AD, Piccini JP
JACC Heart Fail: 30 May 2019; 7:447-456 | PMID: 31146871
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Importance of Nonobstructive Coronary Artery Disease in the Prognosis of Patients With Heart Failure.

Braga JR, Austin PC, Ross HJ, Tu JV, Lee DS
Objectives
This study sought to examine the prognostic significance of nonobstructive coronary artery disease (CAD) in patients with heart failure (HF), as a distinct category apart from those with normal coronary arteries.
Background
Individuals with HF are often dichotomized into ischemic versus nonischemic categories according to the underlying etiology. This binary classification creates a heterogeneous group, combining individuals with nonobstructive CAD with those with normal coronary arteries under the nonischemic label.
Methods
A cohort of individuals with HF and reduced ejection fraction undergoing invasive coronary angiography was examined and linked to administrative databases for outcomes evaluation. Patients were divided into those with normal coronary arteries, nonobstructive disease, and obstructive disease. The primary outcome was the composite of cardiovascular death, nonfatal acute myocardial infarction, nonfatal stroke, or HF hospitalization.
Results
Of 12,814 individuals, 2,656 (20.7%) had normal coronary arteries, 2,254 (17.6%) had nonobstructive CAD, and 7,904 (61.7%) had obstructive CAD. The risk of the primary outcome was increased in the nonobstructive group (hazard ratio [HR]: 1.17; 95% confidence interval [CI]: 1.04 to 1.32; p = 0.01) relative to those with normal coronary arteries. Nonobstructive CAD was associated with an increased hazard of cardiovascular death (HR: 1.82; 95% CI: 1.27 to 2.62; p = 0.001) and death of any cause (HR: 1.18; 95% CI: 1.05 to 1.33; p = 0.005). There were no significant differences in the rate of acute myocardial infarction, stroke, or HF hospitalization.
Conclusions
Among HF patients with reduced ejection fraction, the presence of nonobstructive CAD was independently associated with an increased hazard of the primary composite outcome and death of any cause.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 May 2019; 7:493-501
Braga JR, Austin PC, Ross HJ, Tu JV, Lee DS
JACC Heart Fail: 30 May 2019; 7:493-501 | PMID: 31078476
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Left Ventricular Post-Infarct Remodeling: Implications for Systolic Function Improvement and Outcomes in the Modern Era.

van der Bijl P, Abou R, Goedemans L, Gersh BJ, ... Delgado V, Bax JJ
Objectives
This study sought to investigate the impact of post-infarct left ventricular (LV) remodeling on outcomes in the contemporary era.
Background
LV remodeling after ST-segment elevation myocardial infarction (STEMI) is associated with heart failure and increased mortality. Pivotal studies have mostly been performed in the era of thrombolysis, whereas the long-term prognostic impact of LV remodeling has not been reinvestigated in the current era of primary percutaneous coronary intervention (PCI) and optimal pharmacotherapy.
Methods
Data were obtained from an ongoing registry of patients with STEMI (all treated with primary PCI). Baseline, 3-month, 6-month, and 12-month echocardiograms were analyzed. LV remodeling was defined as a ≥20% increase in LV end-diastolic volume at 3, 6, or 12 months post-infarct. The impact of LV remodeling on outcomes was analyzed.
Results
A total of 1,995 patients with STEMI were studied (mean age 60 ± 12 years, 77% men), 953 (48%) of whom demonstrated remodeling in the first 12 months of follow-up. After a median follow-up of 94 (interquartile range: 69 to 119) months, 225 (11%) patients had died. There was no difference in survival between remodelers and nonremodelers (p = 0.144). However, LV remodelers were more likely to be admitted to hospital for heart failure than were nonremodelers (p < 0.001).
Conclusions
In the contemporary era, in which STEMI is treated with primary PCI and optimal pharmacotherapy, almost one-half of patients demonstrate LV post-infarct remodeling. However, there is no difference in long-term survival between LV remodelers and nonremodelers, and LV remodelers experience a higher rate of heart failure hospitalization, which indicates the need to intensify preventative strategies in these patients.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 02 Dec 2019; epub ahead of print
van der Bijl P, Abou R, Goedemans L, Gersh BJ, ... Delgado V, Bax JJ
JACC Heart Fail: 02 Dec 2019; epub ahead of print | PMID: 31838030
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Sex-Based Differences in Outcomes After Mitral Valve Surgery for Severe Ischemic Mitral Regurgitation: From the Cardiothoracic Surgical Trials Network.

Giustino G, Overbey J, Taylor D, Ailawadi G, ... Lala A, Hung J
Objectives
This study investigated sex-based differences in outcomes after mitral valve (MV) surgery for severe ischemic mitral regurgitation (SIMR).
Background
Whether differences in outcomes exist between men and women after surgery for SIMR remains unknown.
Methods
Patients enrolled in a randomized trial comparing MV replacement versus MV repair for SIMR were included and followed for 2 years. Endpoints for this analysis included all-cause mortality, major adverse cardiovascular and cerebrovascular events (MACCE) (defined as the composite of death, stroke, hospitalization for heart failure, worsening New York Heart Association functional class or MV re-operation), quality of life (QOL), functional status, and percentage of change in left ventricular end-systolic volume index (LVESVI) from baseline through 2 years.
Results
Of 251 patients enrolled in the trial, 96 (38.2%) were women. Compared with men, women had smaller LV volumes and effective regurgitant orifice areas (EROA) but greater EROA/left ventricular (LV) end-diastolic volume ratios. At 2 years, women had higher rates of all-cause mortality (27.1% vs. 17.4%, respectively; adjusted hazard ratio [adjHR]: 1.85; 95% confidence interval [CI]: 1.05 to 3.26; p = 0.03) and of MACCE (49.0% vs. 38.1%, respectively; adjHR: 1.58; 95% CI: 1.06 to 2.37; p = 0.02). Women also reported worse QOL and functional status at 2 years. There were no significant differences in the percentage of change over 2 years in LVESVI between women and men (adjβ: -10.4; 95% CI: -23.4 to 2.6; p = 0.12).
Conclusions
Women with SIMR displayed different echocardiographic features and experienced higher mortality and worse QOL after MV surgery than men. There were no significant differences in the degree of reverse LV remodeling between sexes. (Comparing the Effectiveness of Repairing Versus Replacing the Heart\'s Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation [Severe Ischemic Mitral Regurgitation]; NCT00807040).

Copyright © 2019 American College of Cardiology Foundation. All rights reserved.

JACC Heart Fail: 30 May 2019; 7:481-490
Giustino G, Overbey J, Taylor D, Ailawadi G, ... Lala A, Hung J
JACC Heart Fail: 30 May 2019; 7:481-490 | PMID: 31146872
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Percutaneous Left Axillary Artery Placement of Intra-Aortic Balloon Pump in Advanced Heart Failure Patients.

Bhimaraj A, Agrawal T, Duran A, Tamimi O, ... Torre-Amione G, Estep JD
Objectives
This study presents the largest clinical experience of percutaneously placed axillary intra-aortic balloon pump (IABP) in patients with advanced heart failure.
Background
Transfemoral placement of IABP limits mobility and recuperation in patients who need prolonged support. We had previously reported a novel percutaneous method of IABP placement in the axillary artery and now present our expanded experience with this technique.
Methods
We performed a retrospective chart review of patients with advanced heart failure with percutaneous axillary IABP placement from November 2007 to June 2018 at Houston Methodist Hospital. We defined successful cardiac replacement therapy as heart transplant or left ventricular assist device implantation. We compared patients who had successful cardiac replacement with those who died and those who needed unplanned escalation of mechanical circulatory support.
Results
Of the 195 patients identified, 133 (68%) underwent successful cardiac replacement (120 transplants and 13 left ventricular assist device) as planned. End-organ function improved on IABP support in patients bridged to next therapy. There were 16 patients that died while on IABP support and 18 needed escalation of support. Higher right atrial/wedge ratio, higher right atrial pressure, smaller left ventricular end diastolic dimension, and ischemic cardiomyopathy were associated with death on the IABP in multivariate analysis. Post-transplant and post left ventricular assist device survival for those bridged successfully was 87% and 62%, respectively. Although bedside repositioning was frequent, 37% needed replacement for malfunction. Vascular complications occurred in a minority.
Conclusions
Percutaneous axillary approach for IABP placement is a feasible strategy for prolonged mechanical circulatory support in patients with advanced heart failure.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Mar 2020; 8:313-323
Bhimaraj A, Agrawal T, Duran A, Tamimi O, ... Torre-Amione G, Estep JD
JACC Heart Fail: 30 Mar 2020; 8:313-323 | PMID: 32241538
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Diuretic Strategies for Loop Diuretic Resistance in Acute Heart Failure: The 3T Trial.

Cox ZL, Hung R, Lenihan DJ, Testani JM
Objectives
This study compared combination diuretic strategies in acute heart failure (AHF) complicated by diuretic resistance (DR).
Background
Combination diuretic regimens to overcome loop DR are commonly used but with limited evidence.
Methods
This study was a randomized, double-blinded trial in 60 patients hospitalized with AHF and intravenous (IV) loop DR. Patients were randomized to oral metolazone, IV chlorothiazide, or tolvaptan therapy. All patients received concomitant high-dose IV infusions of furosemide. The primary outcome was 48-h weight loss.
Results
The cohort exhibited DR prior to enrollment, producing 1,188 ± 476 ml of urine in 12 h during high-dose loop diuretic therapy (IV furosemide: 612 ± 439 mg/day). All 3 interventions significantly improved diuretic efficacy (p < 0.001). Compared to metolazone (4.6 ± 2.7 kg), neither IV chlorothiazide (5.8 ± 2.7 kg; 1.2 kg [95% confidence interval [CI]: -2.9 to 0.6; p = 0.292) nor tolvaptan (4.1 ± 3.3 kg; 0.5 kg [95% CI: -1.5 to 2.4; p = 0.456) resulted in more weight loss at 48 h. Median (interquartile range [IQR]) Cumulative urine output increased significantly and did not differ among those receiving metolazone (7.78 [IQR: 6.59 to 10.10] l) and chlorothiazide (8.77 [IQR: 7.37 to 10.86] l; p = 0.245) or tolvaptan (9.70 [IQR: 6.36 to 13.81] l; p = 0.160). Serum sodium decreased less with tolvaptan than with metolazone (+4 ± 5 vs. -1 ± 3 mEq/l; p = 0.001), but 48-h spot urine sodium was lower with tolvaptan (58 ± 25 mmol/l) than with metolazone (104 ± 16 mmol/l; p = 0.002) and with chlorothiazide (117 ± 14 mmol/l; p < 0.001).
Conclusions
In this moderately sized DR trial, weight loss was excellent with the addition of metolazone, IV chlorothiazide, or tolvaptan to loop diuretics, without a detectable between-group difference. (Comparison of Oral or Intravenous Thiazides vs. tolvaptan in Diuretic Resistant Decompensated Heart Failure [3T]; NCT02606253).

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 02 Dec 2019; epub ahead of print
Cox ZL, Hung R, Lenihan DJ, Testani JM
JACC Heart Fail: 02 Dec 2019; epub ahead of print | PMID: 31838029
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Transcatheter Edge-to-Edge Tricuspid Repair for Severe Tricuspid Regurgitation Reduces Hospitalizations for Heart Failure.

Orban M, Rommel KP, Ho EC, Unterhuber M, ... Lurz P, Hausleiter J
Objectives
The goal of this study was to evaluate the effect of transcatheter edge-to-edge tricuspid valve repair (TTVR) for severe tricuspid regurgitation (TR) on hospitalization for heart failure (HHF) and HF-related endpoints.
Background
Patients with severe TR need effective therapies beyond conservative treatment. The impact of TTVR on HHF and HF-related endpoints is unknown.
Methods
Isolated TTVR was performed in 119 patients. Assessments were conducted of New York Heart Association functional class, 6-min walk distance, Minnesota Living with Heart Failure Questionnaire scores, N-terminal pro-B-type natriuretic peptide level, and medication. HHFs were analyzed in the preceding 12 months before and until the longest available follow-up after TTVR. Results were compared with those of 114 patients who underwent combined mitral and tricuspid valve repair.
Results
Procedural success with a reduction to moderate or less TR and no in-hospital death was achieved in 82% of patients. With a median follow-up of 360 days (interquartile range: 187 to 408 days), a durable TR reduction to moderate or less was achieved in 72% of patients (p < 0.001). TTVR reduced the annual rate of HHF by 22% (1.21 to 0.95 HHF/patient-year; p = 0.02), with concomitant clinical improvement in New York Heart Association functional class (patients in class II or lower: 9% to 67%; p < 0.001), 6-min walk distance (+39 m; p = 0.001), and Minnesota Living with Heart Failure Questionnaire score (-6 points; p = 0.02). N-terminal pro-B-type natriuretic peptide level decreased numerically by 783 pg/ml. Diuretic dose before TTVR was increased, but HF medication did not change after TTVR. Procedural success was associated with improved 1-year survival (79% vs. 60%; p = 0.04) and event-free-survival (death + first HHF: 67% vs. 40%; p = 0.001). Transcatheter mitral and tricuspid valve repair-treated patients had comparable outcomes.
Conclusions
TTVR for severe TR is associated with a reduction of HHF and improved clinical outcomes.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Mar 2020; 8:265-276
Orban M, Rommel KP, Ho EC, Unterhuber M, ... Lurz P, Hausleiter J
JACC Heart Fail: 30 Mar 2020; 8:265-276 | PMID: 32241534
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Natriuretic Response Is Highly Variable and Associated With 6-Month Survival: Insights From the ROSE-AHF Trial.

Hodson DZ, Griffin M, Mahoney D, Raghavendra P, ... Mullens W, Testani JM
Objectives
This study sought to describe sodium excretion in acute decompensated heart failure (ADHF) clearly and to evaluate the prognostic ability of urinary sodium and fluid-based metrics.
Background
Sodium retention drives volume overload, with fluid retention largely a passive, secondary phenomenon. However, parameters (urine output, body weight) used to monitor therapy in ADHF measure fluid rather than sodium balance. Thus, the accuracy of fluid-based metrics hinges on the contested assumption that urinary sodium content is consistent.
Methods
Patients enrolled in the ROSE-AHF (Renal Optimization Strategies Evaluation-Acute Heart Failure) trial with 24-h sodium excretion available were studied (n = 316). Patients received protocol-driven high-dose loop diuretic therapy.
Results
Sodium excretion through the first 24 h was highly variable (range 0.12 to 19.8 g; median 3.63 g, interquartile range: 1.85 to 6.02 g) and was not correlated with diuretic agent dose (r = 0.06; p = 0.27). Greater sodium excretion was associated with reduced mortality in a univariate model (hazard ratio: 0.80 per doubling of sodium excretion; 95% confidence interval: 0.66 to 0.95; p = 0.01), whereas gross urine output (p = 0.43), net fluid balance (p = 0.87), and weight change (p = 0.11) were not. Sodium excretion of less than the prescribed dietary sodium intake (2 g), even in the setting of a negative net fluid balance, portended a worse prognosis (hazard ratio: 2.02; 95% confidence interval: 1.17 to 3.46; p = 0.01).
Conclusions
In patients hospitalized with ADHF who were receiving high-dose loop diuretic agents, sodium concentration and excretion were highly variable. Sodium excretion was strongly associated with 6-month mortality, whereas traditional fluid-based metrics were not. Poor sodium excretion, even in the context of fluid loss, portends a worse prognosis.

Copyright © 2019 American College of Cardiology Foundation. All rights reserved.

JACC Heart Fail: 29 Apr 2019; 7:383-391
Hodson DZ, Griffin M, Mahoney D, Raghavendra P, ... Mullens W, Testani JM
JACC Heart Fail: 29 Apr 2019; 7:383-391 | PMID: 31047017
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prior Pacemaker Implantation and Clinical Outcomes in Patients With Heart Failure and Preserved Ejection Fraction.

Shen L, Jhund PS, Docherty KF, Petrie MC, ... Zile MR, McMurray JJV
Objectives
This study examined the relationship between prior pacemaker implantation and clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF).
Background
Conventional right ventricular pacing causes electrical and mechanical left ventricular dyssynchrony and may worsen left ventricular systolic dysfunction and HF. Whether conventional pacing is also associated with worse outcomes in HFpEF is unknown.
Methods
Patient data were pooled from the CHARM-Preserved (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity), I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction), and TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial) studies and were examined for the association between having a pacemaker and the risk of the primary composite of cardiovascular death or HF hospitalization, the individual components of the composite, the 2 main modes of cardiovascular death (i.e., sudden death and pump failure death), and all-cause death in unadjusted and adjusted analyses.
Results
Of the 8,466 patients included, 682 patients (8%) had a pacemaker. Pacemaker patients were older and more often men and had lower body mass indexes, estimated glomerular filtration rates, and blood pressures but higher concentrations of N-terminal pro-B-type natriuretic peptide than those without a pacemaker. The rate of the primary composite outcome in pacemaker patients was almost twice that in patients without a pacemaker (13.6 vs. 7.6 per 100 patient-years of follow up, respectively), with a similar finding for HF hospitalizations (10.8 vs. 5.1 per 100 patient-years, respectively). This risk rate persisted after adjusting for other prognostic variables (hazard ratio [HR] for the composite outcome: 1.17; 95% confidence interval [CI]: 1.02 to 1.33; p = 0.026), driven mainly by HF hospitalization (HR: 1.37; 95% CI: 1.17 to 1.60; p < 0.001). The risk of death was not significantly higher in pacemaker patients in the adjusted analyses.
Conclusions
These findings raise the possibility that right ventricular pacing-induced left ventricular dyssynchrony may be detrimental in HFpEF patients.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Apr 2019; 7:418-427
Shen L, Jhund PS, Docherty KF, Petrie MC, ... Zile MR, McMurray JJV
JACC Heart Fail: 29 Apr 2019; 7:418-427 | PMID: 30981744
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Heart Failure Outcomes and Associated Factors Among Veterans With Human Immunodeficiency Virus Infection.

Erqou S, Jiang L, Choudhary G, Lally M, ... Lin N, Wu WC
Objectives
This study sought to investigate outcomes of heart failure (HF) in veterans living with human immunodeficiency virus (HIV).
Background
Data on outcomes of HF among people living with human immunodeficiency virus (PLHIV) are limited.
Methods
We performed a retrospective cohort study of Veterans Health Affairs data to investigate outcomes of HF in PLHIV. We identified 5,747 HIV+ veterans with diagnosis of HF from 2000 to 2018 and 33,497 HIV- frequency-matched controls were included. Clinical outcomes included all-cause mortality, HF hospital admission, and all-cause hospital admission.
Results
Compared with HIV- veterans with HF, HIV+ veterans with HF were more likely to be black (56% vs. 14%), be smokers (52% vs. 29%), use alcohol (32% vs. 13%) or drugs (37% vs. 8%), and have a higher comorbidity burden (Elixhauser comorbidity index 5.1 vs. 2.6). The mean ejection fraction (EF) (45 ± 16%) was comparable between HIV+ and HIV- veterans. HIV+ veterans with HF had a higher age-, sex-, and race-adjusted 1-year all-cause mortality (30.7% vs. 20.3%), HF hospital admission (21.2% vs. 18.0%), and all-cause admission (50.2% vs. 38.5%) rates. Among veterans with HIV and HF, those with low CD4 count (<200 cells/ml) and high HIV viral load (>75 copies/μl) had worse outcomes. The associations remained statistically significant after adjusting for extensive list of covariates. The incidence of all-cause mortality and HF admissions was higher among HIV+ veterans with ejection fraction <45% Conclusions: HIV+ veterans with HF had higher risk of hospitalization and mortality compared with their HIV- counterparts, with worse outcomes reported for individuals with lower CD4 count, higher viral load, and lower ejection fraction.

Published by Elsevier Inc.

JACC Heart Fail: 05 Apr 2020; epub ahead of print
Erqou S, Jiang L, Choudhary G, Lally M, ... Lin N, Wu WC
JACC Heart Fail: 05 Apr 2020; epub ahead of print | PMID: 32278680
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Differential Associations of Chronic Inflammatory Diseases With Incident Heart Failure.

Prasada S, Rivera A, Nishtala A, Pawlowski AE, ... Lloyd-Jones DM, Feinstein MJ
Objectives
The purpose of this study was to compare the risks of incident heart failure (HF) among a variety of chronic inflammatory diseases (CIDs) and to determine whether risks varied by severity of inflammation within each CID.
Background
Individuals with CIDs are at elevated risk for cardiovascular diseases, but data are limited regarding risk for HF.
Methods
An electronic health records database from a large urban medical system was examined, comparing individuals with CIDs with frequency-matched controls without CIDs, all of whom were receiving regular outpatient care. Rates of incident HF were determined by using the Kaplan-Meier method and subsequently used multivariate-adjusted proportional hazards models to compare HF risks for each CID. Exploratory analyses determined HF risks by proxy measurement of CID severity.
Results
Of 37,636 patients (n = 18,278 patients with CIDs; and n = 19,358 controls without CIDs) there were 960 incident HF cases over a median of 3.6 years. Risks for incident HF were significantly or borderline significantly elevated for patients with systemic sclerosis (hazard ratio [HR]: 7.26; 95% confidence interval [CI]: 5.72 to 9.21; p < 0.01), systemic lupus erythematosus (HR: 3.15; 95% CI: 2.41 to 4.11; p < 0.01), rheumatoid arthritis (HR: 1.39; 95% CI: 1.13 to 1.71; p < 0.01), and human immunodeficiency virus (HR: 1.28; 95% CI: 0.99 to 1.66; p = 0.06). There was no association between psoriasis or inflammatory bowel disease and incident HF, although patients with those CIDs with higher levels of C-reactive protein had higher risks for HF than controls.
Conclusions
Systemic sclerosis and systemic lupus erythematosus were associated with the highest risks of HF, followed by rheumatoid arthritis and HIV. Measurements of inflammation were associated with HF risk across different CIDs.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 05 Apr 2020; epub ahead of print
Prasada S, Rivera A, Nishtala A, Pawlowski AE, ... Lloyd-Jones DM, Feinstein MJ
JACC Heart Fail: 05 Apr 2020; epub ahead of print | PMID: 32278678
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Identification of Frailty in Chronic Heart Failure.

Sze S, Pellicori P, Zhang J, Weston J, Clark AL
Objectives
This study sought to report the prevalence of frailty, classification performance, and agreement among 3 frailty assessment tools and 3 screening tools in chronic heart failure (CHF) patients.
Background
Frailty is common in patients with CHF. There are many available frailty tools, but no standard method for evaluating frailty.
Methods
We used the following frailty screening tools: the clinical frailty scale (CFS); the Derby frailty index; and the acute frailty network frailty criteria. We used the following frailty assessment tools: the Fried criteria; the Edmonton frailty score; and the Deficit Index.
Results
A total of 467 consecutive ambulatory CHF patients (67% male; median age: 76 years; interquartile range [IQR]: 69 to 82 years; median N-terminal pro-B-type natriuretic peptide: 1,156 ng/l [IQR: 469 to 2,463 ng/l]) and 87 control patients (79% male; median age: 73 years; IQR: 69 to 77 years) were studied. The prevalence of frailty using the different tools was higher in CHF patients than in control patients (30% to 52% vs. 2% to 15%, respectively). Frail patients tended to be older, have worse symptoms, higher N-terminal pro-B-type natriuretic peptide levels, and more comorbidities. Of the screening tools, CFS had the strongest correlation and agreement with the assessment tools (correlation coefficient: 0.86 to 0.89, kappa coefficient: 0.65 to 0.72, depending on the frailty assessment tools, all p < 0.001). CFS had the highest sensitivity (87%) and specificity (89%) among screening tools and the lowest misclassification rate (12%) among all 6 frailty tools in identifying frailty according to the standard combined frailty index.
Conclusions
Frailty is common in CHF patients and is associated with increasing age, comorbidities, and severity of heart failure. CFS is a simple screening tool that identifies a similar group using more lengthy assessment tools.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Mar 2019; 7:291-302
Sze S, Pellicori P, Zhang J, Weston J, Clark AL
JACC Heart Fail: 30 Mar 2019; 7:291-302 | PMID: 30738977
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Heart Failure Site-Based Research in the United States: Results of the Heart Failure Society of America Research Network Survey.

Psotka MA, Ammon SE, Fiuzat M, Bozkurt B, ... Jessup M, O\'Connor CM
Objectives
This study sought to determine clinician and scientist involvement in heart failure (HF) clinical research and to describe the challenges of conducting clinical trials in the United States.
Background
Improvements in the current capability, potential, and deficiencies of the HF clinical research infrastructure in the United States are needed in order to enhance efficiency and impact.
Methods
The Heart Failure Society of America (HFSA) distributed an electronic survey regarding HF clinical trial activity for the purpose of understanding the barriers that exist to conducting high-quality HF clinical research.
Results
Overall, 1,794 HFSA members were queried, and 434 members (24%) completed surveys, whereas a total of 7,589 individuals with interest in HF were queried, and 615 completed surveys. Of the respondents, 410 (67%) were actively engaged in HF research and 120 (20%) were interested in research. Most respondents, 270, were physicians (44%); 311 of the total (76% of the total and 80% of physicians) practiced in academic institutions; 333 respondents (81%) had served as principal investigators and 73 (18%) as site coordinators. Respondents active in clinical research usually participated in 1 to 5 trials and enrolled 1 to 20 patients annually. Institutional review board (IRB) approval typically required 3 months, and contract completion required 3 to 6 months per site. The greatest barriers to research were insufficient site budgets, delay in contracting, inability to find participants meeting trial entry criteria, and unavailability of qualified study coordinators.
Conclusions
Many U.S. clinical research sites are constrained by budgetary, staffing, and contractual issues. The HFSA Research Network seeks to unify interested sites and deconstruct barriers to permit high-value HF research.

Copyright © 2019 American College of Cardiology Foundation. All rights reserved.

JACC Heart Fail: 29 Apr 2019; 7:431-438
Psotka MA, Ammon SE, Fiuzat M, Bozkurt B, ... Jessup M, O'Connor CM
JACC Heart Fail: 29 Apr 2019; 7:431-438 | PMID: 30981742
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Medical Management of Heart Failure With Reduced Ejection Fraction in Patients With Advanced Renal Disease.

Hein AM, Scialla JJ, Edmonston D, Cooper LB, DeVore AD, Mentz RJ

Large randomized clinical trials (RCT) supporting guidelines for the management of heart failure with reduced ejection fraction (HFrEF) have typically excluded patients with advanced chronic kidney disease (CKD). Patients with concomitant advanced CKD and HFrEF experience poor cardiovascular outcomes and mortality relative to either disease in isolation and have been shown to consistently receive lower rates of HFrEF guideline-directed medical therapy (GDMT). This review evaluated recent evidence for the use of GDMT in patients with HFrEF and advanced CKD approaching dialysis from RCTs and observational cohorts. The authors also discuss the limitations and challenges inherent in the evidence for GDMT in this population, and offer guidance to clinicians for proper clinical use and future research directions.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Apr 2019; 7:371-382
Hein AM, Scialla JJ, Edmonston D, Cooper LB, DeVore AD, Mentz RJ
JACC Heart Fail: 29 Apr 2019; 7:371-382 | PMID: 31047016
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of Shared Care in Remote Areas for Patients With Left Ventricular Assist Devices.

Yin MY, Strege J, Gilbert EM, Stehlik J, ... Selzman CH, Wever-Pinzon O
Objectives
The aim of this study was to evaluate the impact of a shared-care model on outcomes in patients with left ventricular assist devices (LVADs) living in remote locations.
Background
Health care delivery through shared-care models has been shown to improve outcomes in patients with chronic diseases. However, the impact of shared-care models on outcomes in patients with LVAD is unknown.
Methods
LVAD recipients in the authors\' program (2007 to 2018) were classified based on the levels of care provided and training and resources used: level 1, was defined as outpatient primary care without LVAD-specific care; level 2 was level 1 services and outpatient LVAD-specific care; level 3 was level 2 services and inpatient LVAD-specific care and implantation center (IC). The Kaplan-Meier method was used to compare rates of survival, bleeding, pump thrombosis, infection, neurologic events, and readmissions among levels of care.
Results
A total of 336 patients were included, with 255 patients (75.9%) cared for in shared-care facilities. Median follow-up was 810 (interquartile range: 321 to 1,096) days. In comparison to patients cared for by IC, patients at levels 2 and 3 shared-care centers had similar rates of death, bleeding, neurologic events, pump thromboses, and infections. However, the rates of death, pump thromboses, and infections were higher for level 1 patients than in IC patients.
Conclusions
Shared health care is an effective strategy to deliver care to patients with LVAD living in remote locations. However, patients in shared-care facilities unable to provide LVAD-specific care are at higher risk of unfavorable outcomes. Availability of LVAD-specific care should be strongly considered during patient selection and every effort made to ensure LVAD-specific training and resources are available at shared-care facilities.

Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Mar 2020; 8:302-312
Yin MY, Strege J, Gilbert EM, Stehlik J, ... Selzman CH, Wever-Pinzon O
JACC Heart Fail: 30 Mar 2020; 8:302-312 | PMID: 32241537
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Target Doses of Heart Failure Medical Therapy and Blood Pressure: Insights From the CHAMP-HF Registry.

Peri-Okonny PA, Mi X, Khariton Y, Patel KK, ... Patterson JH, Spertus JA
Objectives
This study sought to determine the rate of use of target doses of foundational guideline-directed medical therapy (GDMT) in a contemporary cohort of patients with heart failure with reduced ejection fraction (HFrEF) across systolic blood pressure (SBP) categories.
Background
Patients with HFrEF are infrequently titrated to recommended doses of GDMT. The relationship between SBP and achieving GDMT target doses is not well studied.
Methods
Patients enrolled in the CHAMP-HF (Change the Management of Patients With Heart Failure) registry without documented intolerance to angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), and beta blockers (BBs) were assessed at enrollment. We estimated the proportion receiving target doses (% of target dose [95% confidence interval (CI)]) based on the most recent American College of Cardiology/American Heart Association/Heart Failure Society of America heart failure guidelines at baseline in all patients, and by SBP category (≥110 vs. <110 mm Hg).
Results
Of the 3,095 patients eligible for analysis, 2,421 (78.2%) had SBP ≥110 mm Hg. The proportion of patients receiving target doses were 18.7% (95% CI: 17.3% to 20.0%; BB), 10.8% (95% CI: 9.7% to 11.9%; ACEI/ARB), and 2.0% (95% CI: 1.5% to 2.5%; ARNI). Among those with SBP <110 mm Hg (n = 674), 17.5% (95% CI: 14.6% to 20.4%; BB), 6.2% (95% CI: 4.4% to 8.1%; ACEI/ARB), and 1.8% (95% CI: 0.8% to 2.8%; ARNI) were receiving target doses. Among those with SBP ≥110 mm Hg (n = 2,421), 19.0% (95% CI: 17.4% to 20.6%; BB), 12.1% (95% CI: 10.8% to 13.4%; ACEI/ARB), and 2.0% (95% CI: 1.5% to 2.6%; ARNI) were receiving target doses.
Conclusions
In a large, contemporary registry of outpatients with chronic HFrEF eligible for treatment with BBs and ACEI/ARB/ARNI, <20% of patients were receiving target doses, even among those with SBP ≥110 mm Hg.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Mar 2019; 7:350-358
Peri-Okonny PA, Mi X, Khariton Y, Patel KK, ... Patterson JH, Spertus JA
JACC Heart Fail: 30 Mar 2019; 7:350-358 | PMID: 30738978
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Urinary Sodium Profiling in Chronic Heart Failure to Detect Development of Acute Decompensated Heart Failure.

Martens P, Dupont M, Verbrugge FH, Damman K, ... Testani J, Mullens W
Objectives
This study sought to determine the relationship between urinary sodium (U) concentration and the pathophysiologic interaction with the development of acute heart failure (AHF) hospitalization.
Background
No data are available on the longitudinal dynamics of U concentration in patients with chronic heart failure (HF), including its temporal relationship with AHF hospitalization.
Methods
Stable, chronic HF patients with either reduced or preserved ejection fraction were prospectively included to undergo prospective collection of morning spot U samples for 30 consecutive weeks. Linear mixed modeling was used to assess the longitudinal changes in U concentration. Patients were followed for the development of the clinical endpoint of AHF.
Results
A total of 80 chronic HF patients (71 ± 11 years of age; an N-terminal pro-B-type natriuretic peptide [NT-proBNP] concentration of 771 [interquartile range: 221 to 1,906] ng/l; left ventricular ejection fraction [LVEF] 33 ± 7%) prospectively submitted weekly pre-diuretic first void morning U samples for 30 weeks. A total of 1,970 U samples were collected, with mean U concentration of 81.6 ± 41 mmol/l. Sodium excretion remained stable over time on a population level (time effect p = 0.663). However, interindividual differences revealed the presence of high (88 mmol/l U [n = 39]) and low (73 mmol/l U [n = 41]) sodium excreters. Only younger age was an independent predictor of high sodium excretion (odds ratio [OR]: 0.91; 95% confidence interval [CI]: 0.83 to 1.00; p = 0.045 per year). During 587 ± 54 days of follow-up, 21 patients were admitted for AHF. Patients who developed AHF had significantly lower U concentrations (F = 24.063; p < 0.001). The discriminating capacity of U concentration to detect AHF persisted after inclusion of NT-proBNP and estimated glomerular filtration rate (eGFR) measurements as random effects (p = 0.041). Furthermore, U concentration dropped (U = 46 ± 16 mmol/l vs. 70 ± 32 mmol/l, respectively; p = 0.003) in the week preceding the hospitalization and returned to the individual\'s baseline (U = 71 ± 22 mmol/l; p = 0.002) following recompensation, while such early longitudinal changes in weight and dyspnea scores were not apparent in the week preceding decompensation.
Conclusions
Overall, U concentration remained relatively stable over time, but large interindividual differences existed in stable, chronic HF patients. Patients who developed AHF exhibited a chronically lower U concentration and exhibited a further drop in U concentration during the week preceding hospitalization. Ambulatory U sample collection is feasible and may offer additional prognostic and therapeutic information.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 29 Apr 2019; 7:404-414
Martens P, Dupont M, Verbrugge FH, Damman K, ... Testani J, Mullens W
JACC Heart Fail: 29 Apr 2019; 7:404-414 | PMID: 31047021
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Central and Peripheral Determinants of Exercise Capacity in Heart Failure Patients With Preserved Ejection Fraction.

Wolsk E, Kaye D, Komtebedde J, Shah SJ, ... Møller JE, Gustafsson F
Objectives
This study sought to discern which central (e.g., heart rate, stroke volume [SV], filling pressure) and peripheral factors (e.g., oxygen use by skeletal muscle, body mass index [BMI]) during exercise were most strongly associated with the presence of heart failure and preserved ejection fraction (HFpEF) as compared with healthy control subjects exercising at the same workload.
Background
The underlying mechanisms limiting exercise capacity in patients with HFpEF are not fully understood.
Methods
In patients with HFpEF (n = 108), the hemodynamic response at peak exercise was measured using right-sided heart catheterization and was compared with that in healthy control subjects (n = 42) at matched workloads to reveal hemodynamic differences that were not attributable to the workload performed. The patients studied were prospectively included in the REDUCE-LAP HF (Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trials and HemReX (Effect of Age on the Hemodynamic Response During Rest and Exercise in Healthy Humans) study. Univariable and multivariable logistic regression models were used to analyze variables associated with HFpEF versus control subjects.
Results
Compared with healthy control subjects, pulmonary capillary wedge pressure (PCWP) and SV were the only independent hemodynamic variables that were associated with HFpEF, a finding explaining 66% (p < 0.0001) of the difference between the groups. When relevant baseline characteristics were added to the base model, only BMI emerged as an additional independent variable, in total explaining of 90% of the differences between groups (p < 0.0001): PCWP (47%), BMI (31%), and SV (12%).
Conclusions
The study identified 3 key variables (PCWP, BMI, and SV) that independently correlate with the presence of patients with HFpEF compared with healthy control subjects exercising at the same workload. Therapies that decrease left-sided heart filling pressures could improve exercise capacity and possibly prognosis.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Mar 2019; 7:321-332
Wolsk E, Kaye D, Komtebedde J, Shah SJ, ... Møller JE, Gustafsson F
JACC Heart Fail: 30 Mar 2019; 7:321-332 | PMID: 30852235
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Endpoints in Heart Failure Drug Development: History and Future.

Fiuzat M, Lowy N, Stockbridge N, Sbolli M, ... Temple R, McMurray J

Heart failure (HF) patients experience a high burden of symptoms and functional limitations, and morbidity and mortality remain high despite successful therapies. The majority of HF drugs in the United States are approved for reducing hospitalization and mortality, while only a few have indications for improving quality of life, physical function, or symptoms. Patient-reported outcomes that directly measure patient\'s perception of health status (symptoms, physical function, or quality of life) are potentially approvable endpoints in drug development. This paper summarizes the history of endpoints used for HF drug approvals in the United States and reviews endpoints that measure symptoms, physical function, or quality of life in HF patients.

Copyright © 2020. Published by Elsevier Inc.

JACC Heart Fail: 05 Apr 2020; epub ahead of print
Fiuzat M, Lowy N, Stockbridge N, Sbolli M, ... Temple R, McMurray J
JACC Heart Fail: 05 Apr 2020; epub ahead of print | PMID: 32278679
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Novel Devices in Heart Failure: BAT, Atrial Shunts, and Phrenic Nerve Stimulation.

Zeitler EP, Abraham WT

The substantial burden of heart failure has inspired innovation in medical device development for decades, and this development continues to be a touchstone in the success story of combined medical and device therapy. Recently, baroreflex activation therapy, interatrial shunts, and phrenic nerve stimulation have shown promise in treating patients with heart failure. We seek to provide background about the design, function, and early clinical experience with these 3 novel heart failure devices. In addition, an understanding of the individual regulatory journey of these devices, some of which is ongoing, is informative for future device development and clinical use.

Copyright © 2020. Published by Elsevier Inc.

JACC Heart Fail: 30 Mar 2020; 8:251-264
Zeitler EP, Abraham WT
JACC Heart Fail: 30 Mar 2020; 8:251-264 | PMID: 32241533
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Income Inequality and Outcomes in Heart Failure: A Global Between-Country Analysis.

Dewan P, Rørth R, Jhund PS, Ferreira JP, ... McMurray JJV,
Objectives
This study examined the relationship between income inequality and heart failure outcomes.
Background
The income inequality hypothesis postulates that population health is influenced by income distribution within a society, with greater inequality associated with worse outcomes.
Methods
This study analyzed heart failure outcomes in 2 large trials conducted in 54 countries. Countries were divided by tertiles of Gini coefficients (where 0% represented absolute income equality and 100% represented absolute income inequality), and heart failure outcomes were adjusted for standard prognostic variables, country per capita income, education index, hospital bed density, and health worker density.
Results
Of the 15,126 patients studied, 5,320 patients lived in Gini coefficient tertile 1 countries (coefficient: <33%), 6,124 patients lived in tertile 2 countries (33% to 41%), and 3,772 patients lived in tertile 3 countries (>41%). Patients in tertile 3 were younger than tertile 1 patients, were more often women, and had less comorbidity and several indicators of less severe heart failure, yet the tertile 3-to-1 hazard ratios (HRs) for the primary composite outcome of cardiovascular death or heart failure hospitalization were 1.57 (95% confidence interval [CI]: 1.38 to 1.79) and 1.48 for all-cause death (95% CI: 1.29 to 1.71) after adjustment for recognized prognostic variables. After additional adjustments were made for per capita income, education index, hospital bed density, and health worker density, these HRs were 1.46 (95% CI: 1.25 to 1.70) and 1.30 (95% CI: 1.10 to 1.53), respectively.
Conclusions
Greater income inequality was associated with worse heart failure outcomes, with an impact similar to those of major comorbidities. Better understanding of the societal and personal bases of these findings may suggest approaches to improve heart failure outcomes.

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Mar 2019; 7:336-346
Dewan P, Rørth R, Jhund PS, Ferreira JP, ... McMurray JJV,
JACC Heart Fail: 30 Mar 2019; 7:336-346 | PMID: 30738981
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Impact of Degree of Left Ventricular Remodeling on Clinical Outcomes From Cardiac Resynchronization Therapy.

Shamoun F, De Marco T, DeMets D, Mei C, ... Feldman AM, Bristow MR
Objectives
This study tested the hypothesis that the extent of left ventricular (LV) eccentric structural remodeling in heart failure with reduced ejection fraction (HFrEF) is directly associated with clinical event responses to cardiac resynchronization therapy (CRT).
Background
Whether the severity of LV structural remodeling influences CRT treatment effects is unknown.
Methods
COMPANION (Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure) trial data were analyzed retrospectively. Left ventricular internal dimensions at end diastole indexed by body surface area (LVEDDI) were measured pre-randomization by 2-dimensional echocardiography. LVEDDI values were stratified around the median value of 35 mm/m, and CRT (including CRT-P [CRT with only pacing capability] and/or CRT-D [CRT with an implantable defibrillator]) treatment effects were assessed and compared by LVEDDI group. Patients assigned to these treatments were compared to those undergoing optimal pharmacologic therapy (OPT) for the outcomes of all-cause mortality (ACM) or ACM and heart-failure hospitalization (ACM/HFH).
Results
In the LVEDDI ≥35 mm/m group (n = 614), CRT vs. OPT was associated with a lower ACM/HFH hazard ratio (HR) (HR: 0.53; 95% confidence interval [CI]: 0.40 to 0.70; p <0.001), whereas in the LVEDDI <35 mm/m group, the CRT vs. OPT ACM/HFH hazard ratio was not statistically significant (HR: 0.80; 95% CI: 0.59 to 1.08; p = 0.15). For ACM alone, in the LVEDDI ≥35 mm/m group, the hazard ratio for CRT-P was 0.59 (95% CI: 0.39 to 0.90; p = 0.012) and for CRT-D 0.50 (95% CI: 0.32 to 0.77; p = 0.002). Neither of the CRT groups showed a statistically significant reduction in ACM in the LVEDDI <35 mm/m group.
Conclusions
Larger versus smaller LVEDDIs are associated with a reduction in ACM with CRT-P or CRT-D treatment, and with a more effective reduction in ACM/HFH for the combined CRT treatment groups.

Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

JACC Heart Fail: 30 Mar 2019; 7:281-290
Shamoun F, De Marco T, DeMets D, Mei C, ... Feldman AM, Bristow MR
JACC Heart Fail: 30 Mar 2019; 7:281-290 | PMID: 30738980
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:
Abstract

Prevalence and Prognostic Implications of Longitudinal Ejection Fraction Change in Heart Failure.

Savarese G, Vedin O, D\'Amario D, Uijl A, ... Lam CSP, Lund LH
Objectives
This study sought to evaluate the incidence, the predictors, and the associations with outcomes of changes in ejection fraction (EF) in heart failure (HF) patients.
Background
EF determines therapy in HF, but information is scarce about incidence, determinants, and prognostic implications of EF change over time.
Methods
Patients with ≥2 EF measurements were made in the Swedish Heart Failure Registry were categorized as heart failure with preserved ejection fraction (HFpEF) (EF ≥50%), heart failure with midrange ejection fraction (HFmrEF) (EF 40% to 49%), or heart failure with reduced ejection fraction (HFrEF) (EF <40%). Changes among categories were recorded, and associations among EF changes, predictors, and all-cause mortality and/or HF hospitalizations were analyzed using logistic and Cox regressions.
Results
Of 4,942 patients at baseline, 18% had HFpEF, 19% had HFmrEF, and 63% had HFrEF. During follow-up, 21% and 18% of HFpEF patients transitioned to HFmrEF and HFrEF, respectively; 37% and 25% of HFmrEF patients transitioned to HFrEF and HFpEF, respectively; and 16% and 10% of HFrEF patients transitioned to HFmrEF and HFpEF, respectively. Predictors of increased EF included use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, female sex, cases of less severe HF, and comorbidities. Predictors of decreased EF included diabetes, ischemic heart disease, and cases of more severe HF. Increased EF was associated with a lower risk (hazard ratio [HR]: 0.62; 95% confidence interval [CI]: 0.55 to 0.69) and decreased EF with a higher risk (HR: 1.15; 95% CI: 1.01 to 1.30) of mortality and/or HF hospitalizations. Prognostic implications were most evident for transitions to and from HFrEF.
Conclusions
Increases in EF occurred in one-fourth of HFrEF and HFmrEF patients, and decreases occurred in more than one-third of patients with HFpEF and HFmrEF. EF change was associated with a wide range of important clinical, treatment, and organizational factors as well as with outcomes, particularly transitions to and from HFrEF.

Copyright © 2019. Published by Elsevier Inc.

JACC Heart Fail: 30 Mar 2019; 7:306-317
Savarese G, Vedin O, D'Amario D, Uijl A, ... Lam CSP, Lund LH
JACC Heart Fail: 30 Mar 2019; 7:306-317 | PMID: 30852236
Go to: DOI | PubMed | PDF | Google Scholar |
Impact:

This program is still in alpha version.