Journal: J Card Fail

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Abstract

The potential roles of osmotic and non-osmotic sodium handling in mediating effects of SGLT2 inhibitors on heart failure.

Bjornstad P, Greasley PJ, Wheeler DC, Chertow GM, ... Heerspink HJL, van Raalte DH
Concomitant type 2 diabetes and chronic kidney disease (CKD) increases the risk of heart failure (HF). Recent STUDIES: demonstrate beneficial effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on CKD progression and HF hospitalization in patients with and without diabetes. In addition to inhibiting glucose reabsorption, SGLT2i reduce proximal tubular sodium reabsorption, possibly leading to transient natriuresis. We review the hypothesis that SGLT2i\'s natriuretic and osmotic diuretic effects mediate their cardio-protective effects. The degree to which these benefits are related to changes in sodium, independent of the kidney, is currently unknown. Aside from effects on osmotically active sodium, we explore the intriguing possibility that SGLT2i could also modulate non-osmotic sodium storage. This alternative hypothesis is based on emerging literature that challenges the traditional two-compartment model of sodium balance to provide support for a three-compartment model that includes the binding of sodium to glycosaminoglycans, such as those in muscles and skin. This recent research on non-osmotic sodium storage, as well as direct cardiac effects of SGLT2i, provides possibilities for other ways in which SGLT2i might mitigate HF risk. Overall, we review the effects of SGLT2i on sodium balance and sensitivity, cardiac tissue, interstitial fluid and plasma volume, and non-osmotic sodium storage.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 17 Jul 2021; epub ahead of print
Bjornstad P, Greasley PJ, Wheeler DC, Chertow GM, ... Heerspink HJL, van Raalte DH
J Card Fail: 17 Jul 2021; epub ahead of print | PMID: 34289398
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Abstract

Prognostic Role of Cardiopulmonary Exercise Testing in Wild Type Transthyretin Amyloid Cardiomyopathy Patients Treated with Tafamidis.

Dalia T, Acharya P, Chan WC, Sauer AJ, ... Porter CB, Shah Z
Background
Prognostic value of cardiopulmonary exercise test (CPET) in wild type transthyretin cardiac amyloidosis (wtATTR) patients treated with Tafamidis is unknown.
Methods
This is a retrospective study of wtATTR patients who underwent baseline CPET and were treated with Tafamidis from 8/31/2018 until 3/31/2020. Univariate logistic and multivariate cox-regression models were used to predict occurrence of primary outcome (composite of mortality, heart transplant and palliative inotrope initiation).
Results
A total of 33 patients were included (median age of 82 years (IQR,79-84), 84% were Caucasians and 79% were males). Majority of patients were NYHA class III at baseline (67%). Baseline median peak oxygen consumption (VO2) and peak circulatory power (CP) were 11.35 (IQR, 8.5-14.2) ml/kg/min and 1485.8 (IQR, 988-2184) mmHg/ml/min, respectively, median VE/VCO2 (Ventilatory efficiency) was 35.7 (IQR, 31-41.2). After 1 year follow up, 11 patients experienced a primary endpoint. Upon multivariate analysis; peak VO2 [HR 0.43 (0.23-0.79), p=0.007], peak CP [HR 0.98 (0.98-0.99), p=0.02], peak VO2/HR (Oxygen pulse) [HR 0.62 (0.39-0.97), p=0.03] and exercise duration >5.5 mins [HR 5.82 (1.29-26.2), p=0.02] were significantly associated with the primary outcome.
Conclusion
Tafamidis treated wtATTR patients who had baseline low peak VO2, peak CP, peak VO2/HR and exercise duration <5.5 minutes had worse outcomes.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 15 Jul 2021; epub ahead of print
Dalia T, Acharya P, Chan WC, Sauer AJ, ... Porter CB, Shah Z
J Card Fail: 15 Jul 2021; epub ahead of print | PMID: 34280522
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Abstract

Pericardial Adipose Tissue Volume and Left Ventricular Assist Device-Associated Outcomes.

Rao VN, Obeid MJ, Rigiroli F, Russell SD, ... Agarwal R, Fudim M
Background
Pericardial adipose tissue (PAT) is associated with adverse cardiovascular outcomes in those with and without established heart failure (HF). However, it is not known whether PAT is associated with adverse outcomes in patients with end-stage HF undergoing LVAD. This study aimed to evaluate the associations between PAT and LVAD-associated outcomes.
Methods and results
We retrospectively measured computed tomography (CT)-derived PAT volumes in 77 consecutive adults who had available chest CT imaging prior to HeartMate 3 LVAD surgery between October 2015-March 2019 at Duke University Hospital. Study groups were divided into above-median (≥219cm3) and below-median (<219cm3) PAT volume. Above-median PAT had a higher proportion of atrial fibrillation, chronic kidney disease, and ischemic cardiomyopathy. Above-median vs. below-median PAT groups had similar Kaplan-Meier incidence rates over two years for 1) composite all-cause mortality, redo-LVAD surgery, and cardiac transplantation (35.9 vs. 32.2%; log-rank p=0.65) and 2) composite incident hospitalizations for HF, gastrointestinal bleeding, LVAD-related infection, and stroke (61.5 vs. 60.5%; log-rank p=0.67).
Conclusions
In patients with end-stage HF undergoing LVAD therapy, PAT is not associated with worse two-year LVAD-related outcomes. The significance of regional adiposity versus obesity in LVAD patients warrants further investigation.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 14 Jul 2021; epub ahead of print
Rao VN, Obeid MJ, Rigiroli F, Russell SD, ... Agarwal R, Fudim M
J Card Fail: 14 Jul 2021; epub ahead of print | PMID: 34274515
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Abstract

Right Heart Dysfunction and Readmission Risk across Left Ventricular Ejection Fraction Status in Patients with Acute Heart Failure.

Santas E, Miñana G, Palau P, Espriella R, ... Bayes-Genís A, Núñez J
Background
Right heart dysfunction (RHD) parameters are increasingly important in heart failure (HF). This study aimed to evaluate the association of advanced RHD with the risk of recurrent admissions across the spectrum of left ventricular ejection fraction (LVEF).
Methods and results
We included 3,383 consecutive patients discharged for acute HF (AHF). Of them, in 1,435 (42.4%) pulmonary artery systolic pressure (PASP) could not be accurately measured, leaving a final sample size of 1,948 patients. Advanced RHD was defined as the combination of a ratio of tricuspid annular plane systolic excursion (TAPSE)/PASP<0.36 and significant tricuspid regurgitation (n=196, 10.2%). Negative binomial regression analyses were used to evaluate the risk of recurrent admissions. At a median follow up of 2.2 years (IQR=0.63-4.71), 3,782 readmissions were registered in 1,296 patients (66.5%). Patients with advanced RHD showed higher readmission rates, but only if LVEF≥40% (p<0.001). In multivariable analyses, this differential association persisted for CV and HF recurrent admissions (p-value for interaction=0.015 and p=0.016; respectively). Advanced RHD was independently associated with the risk of recurrent CV and HF admissions if HF with LVEF≥40% (IRR=1.64; 95% CI: 1.18-2.26; p=0.003; and IRR=1.73; 95% CI: 1.25-2.41; p=0.001;respectively). In contrast, it was not associated with readmission risks if LVEF<40%.
Conclusion
Following an admission for AHF, advanced RHD was strongly associated with a higher risk of recurrent CV and HF admissions, but only in patients with LVEF≥40%.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 13 Jul 2021; epub ahead of print
Santas E, Miñana G, Palau P, Espriella R, ... Bayes-Genís A, Núñez J
J Card Fail: 13 Jul 2021; epub ahead of print | PMID: 34273477
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Abstract

Representativeness of the VICTORIA Trial Population in Clinical Practice: Analysis of the PINNACLE Registry.

Butler J, Djatche LM, Lautsch D, Yang L, Patel MJ, Mentz RJ
Background
. In the VICTORIA trial, vericiguat reduced the risk of cardiovascular mortality and heart failure (HF) hospitalization among patients with heart failure with reduced ejection fraction (HFrEF) and a recent worsening heart failure event (WHFE). The representativeness of VICTORIA population to patients with WHFE in clinical practice is unknown.
Methods and results
. Patients with HF and ejection fraction <45% were identified in the PINNACLE registry and stratified by the occurrence of WHFE. Characteristics and outcomes of PINNACLE patients with and without a WHFE were compared to the VICTORIA population. Of the 14,180 PINNACLE patients with HFrEF identified, 26.5% had a WHFE. The VICTORIA population was similar to PINNACLE patients with a WHFE in mean age (67.3 vs. 66.7), ejection fraction (28.9% vs. 28.3%), body mass index (26.8 vs. 27.6), and comorbidity burden. The rate of HF hospitalization at 1 year was 29.6% in the placebo group of VICTORIA, compared to 35.8% in PINNACLE patients with a WHFE and 13.3% in patients without a WHFE.
Conclusions
. The PINNACLE patients with a WHFE meeting the VICTORIA definition resembled the VICTORIA population in characteristics and outcomes, suggesting that VICTORIA\'s population may be generalizable to patients with a WHFE in clinical practice.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 12 Jul 2021; epub ahead of print
Butler J, Djatche LM, Lautsch D, Yang L, Patel MJ, Mentz RJ
J Card Fail: 12 Jul 2021; epub ahead of print | PMID: 34271161
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Abstract

Use of Outpatient Intravenous Calcitropes for Heart Failure in the United States.

Gottlieb SS, Psotka MA, Desai N, Lindenfeld J, Russo P, Allen LA
Rationale
Outpatient calcitrope infusions-i.e., cardiac inotropes milrinone and dobutamine-are often used for bridge-to-transplantation and palliation in advanced heart failure, but few data exist about real world use of these agents.
Methods and results
We used the Symphony Integrated DataVerse® of commercial, managed Medicare, and Medicaid insurance claims of approximately 280 million people (2012- 2020) to determine the incidence and characteristics of ambulatory calcitrope use. Demographics were calculated, including geographic densities at the Metropolitan Statistical Area level. A population projection normalized for age, sex, and location was extrapolated to the total US population. Ambulatory dispensing of milrinone was found in 10,533 outpatients, 1867 in 2019. Ambulatory dobutamine use was found in 4967 outpatients, 836 in 2019. The 2019 total U.S. projection was 3411 for milrinone and 1281 for dobutamine. The mean age was 62 years for milrinone and 68 for dobutamine. Males represented 70% of use. There were differences between drugs in geographic distribution, with more milrinone use in the Northeast and South and more dobutamine use in the Midwest. Duration of use was 4.6 ± 7.2 months for milrinone and 1.8 ± 4.0 months for dobutamine. 30.6% of patients receiving milrinone subsequently underwent cardiac transplantation or LVAD placement whereas 10% receiving dobutamine went on to advanced therapies. Less than 0.5% of patients received calcitropes while enrolled in hospice care.
Conclusion
More than 4000 patients receive outpatient infusion of calcitropes annually in the outpatient setting. Men are much more likely to receive these medications. A minority of the use is as a bridge to advanced therapies. Geographic variability in use suggests better evidence and consistent guidelines may be helpful.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 11 Jul 2021; epub ahead of print
Gottlieb SS, Psotka MA, Desai N, Lindenfeld J, Russo P, Allen LA
J Card Fail: 11 Jul 2021; epub ahead of print | PMID: 34265464
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Abstract

Sarcoidosis-Related Cardiomyopathy: Current Knowledge, Challenges, and Future Perspectives State-of-the-Art Review.

Gilotra NA, Griffin JM, Pavlovic N, Houston BA, ... Joyce E, Sheikh FH
The prevalence of sarcoidosis-related cardiomyopathy is increasing. Sarcoidosis impacts cardiac function through granulomatous infiltration of the heart, resulting in conduction disease, arrhythmia and/or heart failure. Diagnosis of cardiac sarcoidosis can be challenging and requires clinician awareness as well as differentiation from overlapping diagnostic phenotypes such as other forms of myocarditis and arrhythmogenic cardiomyopathy. Clinical manifestations, extracardiac involvement, histopathology, and advanced cardiac imaging can all lend support to a diagnosis of cardiac sarcoidosis. Mainstay therapy for cardiac sarcoidosis is immunosuppression, however no prospective clinical trials exist to guide management. Patients may progress to developing advanced heart failure or ventricular arrhythmia, for which ventricular assist device therapies or heart transplantation may be considered. The existing knowledge gaps in cardiac sarcoidosis call for an interdisciplinary approach to both patient care and future investigation to improve mechanistic understanding and therapeutic strategies.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 10 Jul 2021; epub ahead of print
Gilotra NA, Griffin JM, Pavlovic N, Houston BA, ... Joyce E, Sheikh FH
J Card Fail: 10 Jul 2021; epub ahead of print | PMID: 34260889
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Abstract

The Additive Prognostic Value of Serial Plasma Interleukin-6 Levels over Changes in Brain Natriuretic Peptide in Patients with Acute Heart Failure.

Markousis-Mavrogenis G, Tromp J, Mentz RJ, O\'Connor CM, ... Voors AA, van der Meer P
Background
Elevated plasma interleukin-6 (IL-6) concentrations are frequently observed in patients with acute heart failure (AHF). However, the predictive value of serial IL-6 measurements beyond brain natriuretic peptide (BNP) remains poorly characterized.
Methods and results
This was a retrospective analysis of the PROTECT cohort (2033 patients with AHF). Plasma IL-6 and BNP levels were determined on days 1, 2, 7 and 14 after admission for AHF in 1591 (78.3%), 1462 (71.9%), 1445 (71.1%) and 1451 (71.4%) patients, respectively. The primary endpoint was 180-day all-cause mortality. The median day-1 IL-6 concentration was 11.1 pg/mL (IQR: 6.6, 20.9) and decreased to 10.1 pg/mL (IQR: 5.6-18.5) at day-7. Higher cross-sectional IL-6 concentrations at all time-points predicted the primary endpoint, independent of a risk model for this cohort and changes in BNP. Each doubling of IL-6 between day-1 and day-7 predicted the primary endpoint independent of baseline IL-6 concentrations, the risk model, baseline BNP and changes in BNP [HR (95% CI): 1.18 (1.07-1.30), p=0.0013]. Collectively, 214 (17%) patients experienced at least a doubling of their IL-6 concentrations between day-1 and day-7.
Conclusions
We demonstrate that the temporal evolution patterns of IL-6 in patients with AHF have additive prognostic value independent of changes in BNP.

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

J Card Fail: 29 Jun 2021; 27:808-811
Markousis-Mavrogenis G, Tromp J, Mentz RJ, O'Connor CM, ... Voors AA, van der Meer P
J Card Fail: 29 Jun 2021; 27:808-811 | PMID: 33497808
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Abstract

Generalizability of HFA-PEFF and HFPEF Diagnostic Algorithms and Associations With Heart Failure Indices and Proteomic Biomarkers: Insights From PROMIS-HFpEF.

Faxen UL, Venkateshvaran A, Shah SJ, Lam CSP, ... Hage C, Lund LH
Background
Diagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging. We aimed to evaluate the generalizability of the HFA-PEFF (Heart Failure Association Pre-test assessment, Echocardiography & natriuretic peptide, Functional testing, Final etiology) and weighted H2FPEF (Heavy, 2 or more Hypertensive drugs, atrial Fibrillation, Pulmonary hypertension, Elder age > 60, elevated Filling pressures) diagnostic algorithms and associations with HF severity, coronary microvascular dysfunction and proteomic biomarkers.
Methods and results
Diagnostic likelihood of HFpEF was calculated in the prospective, multinational PROMIS-HFpEF (Prevalence of microvascular dysfunction in HFpEF) cohort using current European Society of Cardiology recommendations, HFA-PEFF and H2FPEF algorithms. Associations between the 2 algorithms and left atrial function, Doppler-based coronary flow reserve, 6-minute walk test, quality of life, and proteomic biomarkers were investigated. Of 181 patients with an EF of ≥50%, 129 (71%) and 94 (52%) fulfilled criteria for high likelihood HFpEF as per HFA-PEFF and H2FPEF, and 28% and 46% were classified as intermediate likelihood, requiring additional hemodynamic testing. High likelihood HFpEF patients were older with higher prevalence of atrial fibrillation and lower global longitudinal strain and left atrial reservoir strain (P < .001 for all variables). left atrial reservoir strain and global longitudinal strain were inversely associated with both HFA-PEFF and H2FPEF scores (TauB = -0.35 and -0.46 and -0.21 and -0.31; P < .001 for all). There were no associations between scoring and 6-minute walk test, quality of life, and coronary flow reserve. Both scores were associated with biomarkers related to inflammation, oxidative stress, and fibrosis.
Conclusions
Although the HFA-PEFF and H2FPEF scores were associated with measures of HF severity and biomarkers related to HFpEF, they demonstrated a modest and differential ability to identify HFpEF noninvasively, necessitating additional functional testing to confirm the diagnosis.

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

J Card Fail: 29 Jun 2021; 27:756-765
Faxen UL, Venkateshvaran A, Shah SJ, Lam CSP, ... Hage C, Lund LH
J Card Fail: 29 Jun 2021; 27:756-765 | PMID: 33647474
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Abstract

Dynamic Assessment of Pulmonary Artery Pulsatility Index Provides Incremental Risk Assessment for Early Right Ventricular Failure After Left Ventricular Assist Device.

Gonzalez MH, Wang Q, Yaranov DM, Albert C, ... Starling RC, Joyce E
Background
The pulmonary artery pulsatility index (PAPi) has been studied to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation, but only as a single time point before LVAD implantation. Multiple clinical factors and therapies impact RV function in pre-LVAD patients. Thus, we hypothesized that serial PAPi measurements during cardiac intensive care unit (CICU) optimization before LVAD implantation would provide incremental risk stratification for early RVF after LVAD implantation.
Methods and results
Consecutive patients who underwent sequential pulmonary artery catherization with cardiac intensive care optimization before durable LVAD implantation were included. Serial hemodynamics were reviewed retrospectively across the optimization period. The optimal PAPi was defined by the initial PAPi + the PAPi at optimized hemodynamics. RVF was defined as need for a right ventricular assist device or prolonged inotrope use (>14 days postoperatively). Patients with early RVF had significantly lower mean optimal PAPi (3.5 vs 7.5, P < .001) compared with those who did not develop RVF. After adjusting for established risk factors of early RVF after LVAD implantation, the optimal PAPi was independently and incrementally associated with early RVF after LVAD implantation (odds ratio 0.64, 95% confidence interval 0.532-0.765, P < .0001).
Conclusions
Optimal PAPi achieved during medical optimization before LVAD implantation provides independent and incremental risk stratification for early RVF, likely identifying dynamic RV reserve.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Jun 2021; 27:777-785
Gonzalez MH, Wang Q, Yaranov DM, Albert C, ... Starling RC, Joyce E
J Card Fail: 29 Jun 2021; 27:777-785 | PMID: 33640481
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Abstract

PCSK9 Inhibitors in Heart Transplant Patients: Safety, Efficacy, and Angiographic Correlates.

Sammour Y, Dezorzi C, Austin BA, Borkon AM, ... Kao AC, Sperry BW
Background
Statins are recommended in heart transplant patients, but are sometimes poorly tolerated. Alternative agents are often considered including proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i). We sought to investigate the use of PCSK9i after heart transplantation.
Methods and results
We identified patients who received a heart transplant from 1999 to 2019 and were started on PCSK9i at our institution. Clinical, laboratory, and coronary angiography with intravascular ultrasound results were compared. Among 65 patients initiated on PCSK9i (48 for statin intolerance and 17 for refractory hyperlipidemia), the median time from transplant was 5.5 years (interquartile range [IQR], 2.8-9.9 years) with a median PCSK9 treatment duration of 1.6 years (IQR, 0.8-3.2 years) and 80% still on treatment. Evolocumab was used in 73.8%, alirocumab in 12.3%, and both in 13.8% owing to insurance coverage. All patients required prior authorization; initial denial occurred in 18.5% and 32.3% had denials in subsequent years. The median low-density lipoprotein cholesterol decreased from 130 mg/dL (IQR, 102-148 mg/dL) to 55 mg/dL (IQR, 35-74 mg/dL) after starting PCSK9i (P < .001), with 72% of patients achieving a low-density lipoprotein cholesterol of <70 mg/dL after treatment. There were also significant reductions of total cholesterol, non-high-density lipoprotein cholesterol, total/high-density lipoprotein cholesterol ratio, and triglycerides, with a modest increase in high-density lipoprotein cholesterol. These changes were durable at latest follow-up. In 33 patients with serial coronary angiography and intravascular ultrasound, PCSK9i were associated with stable coronary plaque thickness and lumen area.
Conclusions
Among heart transplant recipients, PCSK9i are effective in lowering cholesterol levels and stabilizing coronary intimal hyperplasia with minimal side effects. Despite favorable effects, access and affordability remain a challenge.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Jun 2021; 27:812-815
Sammour Y, Dezorzi C, Austin BA, Borkon AM, ... Kao AC, Sperry BW
J Card Fail: 29 Jun 2021; 27:812-815 | PMID: 33753241
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Abstract

Iron Deficiency Is Associated With Impaired Biventricular Reserve and Reduced Exercise Capacity in Patients With Unexplained Dyspnea.

Martens P, Claessen G, Van De Bruaene A, Verbrugge FH, ... Dendale P, Verwerft J
Background
Iron deficiency (ID) is frequent and associated with diminished exercise capacity in heart failure (HF), but its contribution to unexplained dyspnea without a HF diagnosis at rest remains unclear.
Methods and results
Consecutive patients with unexplained dyspnea and normal echocardiography and pulmonary function tests at rest underwent prospective standardized cardiopulmonary exercise testing with echocardiography in a tertiary care dyspnea clinic. ID was defined as ferritin of <300 µg/L and a transferrin saturation of <20% and its impact on peak oxygen uptake (peakVO2), biventricular response to exercise, and peripheral oxygen extraction was assessed. Of 272 patients who underwent cardiopulmonary exercise testing with echocardiography, 63 (23%) had ID. For a similar respiratory exchange ratio, patients with ID had lower peakVO2 (14.6 ± 7.6 mL/kg/minvs 17.8 ± 8.8 mL/kg/min; P = .009) and maximal workload (89 ± 50 watt vs 108 ± 56 watt P = .047), even after adjustment for the presence of anemia. At rest, patients with ID had a similar left ventricular and right ventricular (RV) contractile function. During exercise, patients with ID had lower cardiac output reserve (P < .05) and depressed RV function by tricuspid s\' (P = .004), tricuspid annular plane systolic excursion (P = .034), and RV end-systolic pressure-area ratio (P = .038), with more RV-pulmonary artery uncoupling measured by tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure ratio (P = .023). RV end-systolic pressure-area ratio change from rest to peak exercise, as a load-insensitive metric of RV contractility, was lower in patients with ID (2.09 ± 0.72 mm Hg/cm2 vs 2.58 ± 1.14 mm Hg/cm2; P < .001). ID was associated with impaired peripheral oxygen extraction (peakVO2/peak cardiac output; P = .036). Cardiopulmonary exercise testing with echocardiography resulted in a diagnosis of HF with preserved ejection fraction in 71 patients (26%) based on an exercise E/e\' ratio of >14, with equal distribution in patients with (28.6%) or without ID (25.4%, P = .611). None of these findings were influenced in a sensitivity analysis adjusted for a final diagnosis of HFpEF as etiology for the unexplained dyspnea.
Conclusions
In patients with unexplained dyspnea without clear HF at rest, ID is common and associated with decreased exercise capacity, diminished biventricular contractile reserve, and decreased peripheral oxygen extraction.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Jun 2021; 27:766-776
Martens P, Claessen G, Van De Bruaene A, Verbrugge FH, ... Dendale P, Verwerft J
J Card Fail: 29 Jun 2021; 27:766-776 | PMID: 33838251
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Abstract

Associations of Angiopoietins With Heart Failure Incidence and Severity.

Peplinski BS, Houston BA, Bluemke DA, Kawut SM, ... Tedford RJ, Leary PJ
Background
Angiopoietin-1 and 2 (Ang1, Ang2) are important mediators of angiogenesis. Angiopoietin levels are perturbed in cardiovascular disease, but it is unclear whether angiopoietin signaling is causative, an adaptive response, or merely epiphenomenon of disease activity.
Methods and results
In a cohort free of cardiovascular disease at baseline (Multi-Ethnic Study of Atherosclerosis [MESA]), relationships between angiopoietins, cardiac morphology, and subsequent incidence of heart failure or cardiovascular death were evaluated. In cohorts with pulmonary arterial hypertension or left heart disease, associations between angiopoietins, invasive hemodynamics, and adverse clinical outcomes were evaluated. In MESA, Ang2 was associated with a higher incidence of heart failure or cardiovascular death (hazard ratio 1.21 per standard deviation, P < .001). Ang2 was associated with increased right atrial pressure (pulmonary arterial hypertension cohort) and increased wedge pressure and right atrial pressure (left heart disease cohort). Elevated Ang2 was associated with mortality in the pulmonary arterial hypertension cohort.
Conclusions
Ang2 was associated with incident heart failure or death among adults without cardiovascular disease at baseline and with disease severity in individuals with existing heart failure. Our finding that Ang2 is increased before disease onset and that elevations reflect disease severity, suggests Ang2 may contribute to heart failure pathogenesis.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Jun 2021; 27:786-795
Peplinski BS, Houston BA, Bluemke DA, Kawut SM, ... Tedford RJ, Leary PJ
J Card Fail: 29 Jun 2021; 27:786-795 | PMID: 33872759
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Abstract

Cardiac Thyrotropin-releasing Hormone Inhibition Improves Ventricular Function and Reduces Hypertrophy and Fibrosis After Myocardial Infarction in Rats.

Schuman ML, Peres Diaz LS, Aisicovich M, Ingallina F, ... Landa MS, García SI
Background
Cardiac thyrotropin-releasing hormone (TRH) is a tripeptide with still unknown functions. We demonstrated that the left ventricle (LV) TRH system is hyperactivated in spontaneously hypertensive rats and its inhibition prevented cardiac hypertrophy and fibrosis. Therefore, we evaluated whether in vivo cardiac TRH inhibition could improve myocardial function and attenuate ventricular remodeling in a rat model of myocardial infarction (MI).
Methods and results
In Wistar rats, MI was induced by a permanent left anterior descending coronary artery ligation. A coronary injection of a specific small interfering RNA against TRH was applied simultaneously. The control group received a scrambled small interfering RNA. Cardiac remodeling variables were evaluated one week later. In MI rats, TRH inhibition decreased LV end-diastolic (1.049 ± 0.102 mL vs 1.339 ± 0.102 mL, P < .05), and end-systolic volumes (0.282 ± 0.043 mL vs 0.515 ± 0.037 mL, P < .001), and increased LV ejection fraction (71.89 ± 2.80% vs 65.69 ± 2.85%, P < .05). Although both MI groups presented similar infarct size, small interfering RNA against TRH treatment attenuated the cardiac hypertrophy index and myocardial interstitial collagen deposition in the peri-infarct myocardium. These effects were accompanied by attenuation in the rise of transforming growth factor-β, collagen I, and collagen III, as well as the fetal genes (atrial natriuretic peptide, B-type natriuretic peptide, and beta myosin heavy chain) expression in the peri-infarct region. In addition, the expression of Hif1α and vascular endothelial growth factor significantly increased compared with all groups.
Conclusions
Cardiac TRH inhibition improves LV systolic function and attenuates ventricular remodeling after MI. These novel findings support the idea that TRH inhibition may serve as a new therapeutic strategy against the progression of heart failure.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Jun 2021; 27:796-807
Schuman ML, Peres Diaz LS, Aisicovich M, Ingallina F, ... Landa MS, García SI
J Card Fail: 29 Jun 2021; 27:796-807 | PMID: 33865967
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Abstract

Profile of Patients Hospitalized for Heart Failure Who Leave Against Medical Advice.

Mitchell JE, Chesler R, Zhang S, Matsouaka RA, ... Chang NL, Fonarow GC
Background
There is a paucity of information on patients hospitalized with heart failure (HF) who leave against medical advice (AMA). We sought to identify patient and hospital characteristics and outcomes of patients with HF who left AMA compared with those conventionally discharged to home.
Methods and results
Using the Get With The Guidelines-Heart Failure registry, data were analyzed from January 2010 to June 2019. In addition, outcomes were examined from a subset of hospitalizations with Medicare-linked claims between January 2010 and November 2015. The fully eligible population included 561,823 patients and the Medicare-linked subset included 74,502 patients. In total, 8747 patients (1.56%) left AMA. The proportion of patients leaving AMA increased from 1.1% to 2.1% over the years of study. Patients leaving a HF hospitalization AMA, compared with patients conventionally discharged to home, were more likely younger, minorities, Medicaid covered, or uninsured. The Medicare-linked subset of patients who left AMA had substantially higher 30-day and 12-month readmission rates and higher mortality at each assessment point over 12 months compared with patients who were conventionally discharged to home. After risk adjustments, the hazard ratio of mortality in the Medicare-linked subset AMA group compared with the conventionally discharged to home group was 1.25 (95% confidence interval, 1.03-1.51; P = .005).
Conclusions
One in 64 hospitalized patients with HF left AMA. An AMA discharge status was associated with higher risk for adverse 30-day and 12-month outcomes compared with being conventionally discharged home. Strategies that identify patients at risk of leaving AMA and policies to direct interventional strategies are warranted.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Jun 2021; 27:747-755
Mitchell JE, Chesler R, Zhang S, Matsouaka RA, ... Chang NL, Fonarow GC
J Card Fail: 29 Jun 2021; 27:747-755 | PMID: 33864931
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Abstract

Heart Failure Association, Heart Failure Society of America, and Japanese Heart Failure Society Position Statement on Endomyocardial Biopsy.

Seferović PM, Tsutsui H, Mcnamara DM, Ristić AD, ... Coats AJS, Starling RC
Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumors. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples has significantly improved the diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (1) an overview of the practical approach to EMB, (2) an update on indications for EMB, (3) a revised plan for heart transplant rejection surveillance, (4) the impact of multimodality imaging on EMB, and (5) the current clinical practice in the worldwide use of EMB.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 29 Jun 2021; 27:727-743
Seferović PM, Tsutsui H, Mcnamara DM, Ristić AD, ... Coats AJS, Starling RC
J Card Fail: 29 Jun 2021; 27:727-743 | PMID: 34022400
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Abstract

US Nationwide Prescription Fill Patterns of Evidence-Based Medical Therapies for Heart Failure During the COVID-19 Pandemic.

Vaduganathan M, Li D, van Meijgaard J, Warraich HJ
Background
Maintaining a steady medication supply during a public health crisis is a major health priority. We leveraged a large US pharmacy claims database to understand utilization of evidence-based therapies used in heart failure (HF) care during the coronavirus disease-2019 (COVID-19) pandemic.
Methods
We analyzed 27,027,650 individual claims from an all-payer pharmacy claims database across 56,155 chain, independent, and mail-order pharmacies in 14,164 zip codes in 50 states. Prescriptions dispensed (in 2-week intervals) of evidence-based HF therapies in 2020 were indexed to comparable timeframes in 2019. We normalized these year-over-year changes in HF medical therapies relative to those observed with a stable basket of drugs.
Results
Fills of losartan, lisinopril, carvedilol, and metoprolol all peaked in the weeks of March 2020 and demonstrated trajectories thereafter that were relatively consistent with the reference set of drugs. Fills of spironolactone (+4%) and eplerenone (+18%) showed modest trends towards increased relative use during 2020. Fills of empagliflozin (+75%), dapagliflozin (+65%), and sacubitril/valsartan (+61%) showed striking longitudinal increases throughout 2020 that deviated substantially from year-over-year trends of the overall basket of drugs. For all 3 therapies, fills of all quantity sizes relatively increased throughout 2020. For both generic and brand-name therapies, prescription fill patterns from mail order pharmacies increased substantially over expected trends beginning in March 2020
Conclusion:
Prescription fills of most established generic therapies used in HF care were maintained, while those of sacubitril/valsartan and the sodium-glucose cotransporter-2 inhibitors steeply increased during the COVID-19 pandemic. These nationwide pharmacy claims data provide reassurance about therapeutic access to evidence-based medications used in HF care during a public health crisis.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 27 Jun 2021; epub ahead of print
Vaduganathan M, Li D, van Meijgaard J, Warraich HJ
J Card Fail: 27 Jun 2021; epub ahead of print | PMID: 34214650
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Abstract

Clinical Outcome Predictions for the VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) Trial.

Mentz RJ, Mulder H, Mosterd A, Sweitzer NK, ... Hernandez AF, VICTORIA Study Group
Background
The prediction of outcomes in patients with heart failure (HF) may inform prognosis, clinical decisions regarding treatment selection, and new trial planning. The VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction included high-risk patients with HF with reduced ejection fraction and a recent worsening HF event. The study participants had a high event rate despite the use of contemporary guideline-based therapies. To provide generalizable predictive data for a broad population with a recent worsening HF event, we focused on risk prognostication in the placebo group.
Methods and results
Data from 2524 participants randomized to placebo with chronic HF (New York Heart Association functional class II-IV) and an ejection fraction of less than 45% were studied and backward variable selection was used to create Cox proportional hazards models for clinical end points, selecting from 66 candidate predictors. Final model results were produced, accounting for missing data, and nonlinearities. Optimism-corrected c-indices were calculated using 200 bootstrap samples. Over a median follow-up of 10.4 months, the primary outcome of HF hospitalization or cardiovascular death occurred in 972 patients (38.5%). Independent predictors of increased risk for the primary end point included HF characteristics (longer HF duration and worse New York Heart Association functional class), medical history (prior myocardial infarction), and laboratory values (higher N-terminal pro-hormone B-type natriuretic peptide, bilirubin, urate; lower chloride and albumin). Optimism-corrected c-indices were 0.68 for the HF hospitalization/cardiovascular death model, 0.68 for HF hospitalization/all-cause death, 0.72 for cardiovascular death, and 0.73 for all-cause death.
Conclusions
Predictive models developed in a large diverse clinical trial with comprehensive clinical and laboratory baseline data-including novel measures-performed well in high-risk patients with HF who were receiving excellent guideline-based clinical care.
Clinical trial registration
Clinicaltrials.gov identifier, NCT02861534.Lay Summary: Patients with heart failure may benefit from tools that help clinicians to better understand a patient\'s risk for future events like hospitalization. Relatively few risk models have been created after the worsening of heart failure in a contemporary cohort. We provide insights on the risk factors for clinical events from a recent, large, global trial of patients with worsening heart failure to help clinicians better understand and communicate prognosis and select treatment options.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 23 Jun 2021; epub ahead of print
Mentz RJ, Mulder H, Mosterd A, Sweitzer NK, ... Hernandez AF, VICTORIA Study Group
J Card Fail: 23 Jun 2021; epub ahead of print | PMID: 34217593
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Abstract

Management of Cardiac Sarcoidosis Using Mycophenolate Mofetil as a Steroid Sparing Agent.

Griffin JM, Chasler J, Wand AL, Okada DR, ... Chen ES, Gilotra NA
Background
Cardiac sarcoidosis (CS) is a major cause of morbidity and mortality in patients with systemic sarcoidosis. Steroid sparing agents are increasingly used, despite lack of randomized trials or published guidelines to direct treatment.
Methods
This retrospective study included 77 patients with CS treated with prednisone monotherapy (n=32) or a combination with mycophenolate mofetil (MMF) (n=45) between 2003 and 2018. Baseline characteristics and clinical outcomes were evaluated.
Results
Patients were mean age 53±11 years at CS diagnosis, 66.2% male and 35.1% Black. Total exposure to maximum prednisone dose (initial prednisone dose x days at dose) was lower in the combination therapy group (1440 mg [1200, 2760] vs 2710 mg [1200, 5080]; p = 0.06). On 18F-fluorodeoxyglucose (FDG) positron emission tomography, both groups demonstrated a significant decrease in cardiac maximum standardized uptake value post-treatment: median decrease 3.9 (IQR 2.7, 9.0; p=0.002) and 2.9 (IQR 0, 5.0; p=0.001) for prednisone monotherapy and combination therapy, respectively. Most patients experienced improvement or complete resolution in qualitative cardiac FDG uptake (92.3% and 70.4% for prednisone and combination therapy groups, respectively). MMF was well tolerated.
Conclusions
MMF in combination with prednisone for treatment of CS may minimize corticosteroid exposure and reduce cardiac inflammation without significant adverse effects.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 20 Jun 2021; epub ahead of print
Griffin JM, Chasler J, Wand AL, Okada DR, ... Chen ES, Gilotra NA
J Card Fail: 20 Jun 2021; epub ahead of print | PMID: 34166800
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Abstract

The Impact of Depression on Outcomes in Patients with Heart Failure and Reduced Ejection Fraction Treated in the GUIDE-IT Trial.

Chouairi F, Fuery MA, Mullan CW, Caraballo C, ... Desai NR, Ahmad T
Background
It remains unclear why depression is associated with adverse outcomes in heart failure (HF) patients. We examine the relationship between depression and clinical outcomes among patients with HF and reduced ejection fraction (HFrEF) managed with guideline directed medical therapy (GDMT).
Methods
Using the GUIDE-IT trial, 894 patients with HFrEF were stratified according to a history of depression, and Cox proportional hazards regression modeling was used to examine the association with outcomes.
Results
140 patients (16%) of the overall cohort had depression. They tended to be female (29% vs. 46%; P<0.001) and white (67% vs. 53%, P=0.002). There were no differences in GDMT rates at baseline or at 90 days; nor were there differences in target doses of these therapies achieved at 90 days (NS, all). NT-proBNP levels at all time points were similar between cohorts (P>0.05, all). After adjustment, depression was associated with all-cause hospitalizations [HR 1.42 (CI: 1.11-1.81), P<0.01)], cardiovascular death [HR 1.69 (CI: 1.07-2.68, P=0.025)], and all-cause mortality [HR 1.54 (CI: 1.03-2.32, P=0.039)].
Conclusion
Depression impacts clinical outcomes in HF regardless of GDMT intensity and NT-proBNP levels. This underscores the need for a focus on mental health in parallel to achievement of optimal GDMT in these patients.
Trial registration
NCT01685840, https://clinicaltrials.gov/ct2/show/NCT01685840.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 20 Jun 2021; epub ahead of print
Chouairi F, Fuery MA, Mullan CW, Caraballo C, ... Desai NR, Ahmad T
J Card Fail: 20 Jun 2021; epub ahead of print | PMID: 34166799
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Abstract

Selfcare Management Intervention in Heart Failure (SMART-HF) -A multicentre randomized controlled trial.

Sahlin D, Rezanezad B, Edvinsson ML, Bachus E, Melander O, Gerward S
Background
Self-care behaviour is important in avoiding hospitalization for patients with heart failure (HF) and refers to those activities performed with the intention of improving or restoring health and well-being, as well as treating or preventing disease. The purpose was to study the effects of a home-based mobile device on self-care behaviour and hospitalizations in a representative HF-population.
Methods and results
SMART-HF is a randomized controlled multi-centre clinical trial, where patients were randomized 1:1 to receive standard care (control group, CG) or intervention with a home-based tool designed to enhance self-care behaviour (intervention group, IG) and followed for 240 days. The tool educates the patient about HF, monitors objective and subjective symptoms and adjusts loop-diuretics. The primary outcome is self-care as measured by the European Heart Failure Self-care behaviour scale and the secondary outcome is HF related in-hospital days. A total of 124 patients were recruited and 118 were included in the analyses (CG: n = 60, IG: n = 58). The mean age was 79 years, 39% were female, and 45% had an EF < 40%. Self-care was significantly improved in the IG compared to the CG (21.5 [13.25; 28] vs 26 [18; 29.75], p = 0.014). Patients in the IG spent significantly less time in the hospital admitted for HF (2,2 days less, RR: 0.48; 95% CI: 0.32 - 0.74; p = 0.001) .
Conclusion
The device significantly improved self-care behaviour and reduced in-hospital days in a relevant HF population.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 19 Jun 2021; epub ahead of print
Sahlin D, Rezanezad B, Edvinsson ML, Bachus E, Melander O, Gerward S
J Card Fail: 19 Jun 2021; epub ahead of print | PMID: 34161807
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Abstract

PRESENCE OF INTRACARDIAC THROMBUS AT THE TIME OF LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION IS ASSOCIATED WITH INCREASED RISK OF STROKE AND DEATH.

Bravo CA, Fried JA, Willey JZ, Javaid A, ... Yuzefpolskaya M, Colombo PC
Background
Heart failure predisposes to intracardiac thrombus (ICT) formation. There is limited data on prevalence and impact of pre-existing ICT on postoperative outcomes in LVAD patients. We examined the risk for stroke and death in this patient population.
Methods
We retrospectively studied patients who were implanted with HeartMate (HM) II or HM3 between 2/2009 and 3/2019. Preoperative transthoracic echocardiograms, intraoperative transesophageal echocardiograms and operative reports were reviewed to identify ICT.
Results
525 LVAD patients (median age 60.6 years, 81.8% male, 372 HMII and 151 HM3) were included. An ICT was identified in 44 (8.4%) patients. During the follow up, 43 patients experienced a stroke and 55 died. After multivariable adjustment, presence of ICT increased the risk for the composite of stroke or death at 6-month (hazard ratio [HR]: 1.82, 95% confidence interval [CI]: 1.00-3.33, p=0.049). Patients with ICT were also at higher risk for stroke (HR: 2.45, 95% CI: 1.14-5.28, p=0.021) and death (HR: 2.36, 95% CI: 1.17-4.79 p=0.016) at 6 months follow up.
Conclusions
Presence of ICT is an independent predictor of stroke and death at 6-month after LVAD. Additional studies are needed to help risk stratify and optimize perioperative management of this patient population.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 19 Jun 2021; epub ahead of print
Bravo CA, Fried JA, Willey JZ, Javaid A, ... Yuzefpolskaya M, Colombo PC
J Card Fail: 19 Jun 2021; epub ahead of print | PMID: 34161806
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Abstract

Safety of Contemporary Heart Failure Therapy in Patients with Continuous-Flow Left Ventricular Assist Devices.

Schnettler JK, Roehrich L, Just IA, Pergantis P, ... Potapov E, Schoenrath F
Background
There are limited data available concerning the safety, optimal administration and benefits of contemporary heart failure therapy in patients after left ventricular assist device (LVAD) implantation.
Methods
Between 2015 and 2019, 257 patients underwent LVAD implantation and were included in this observational study. Oral heart failure therapy was initiated and up-titrated during the further course. After propensity matching and excluding patients with immediate postoperative treatment in an affiliated center with different medical standards, hospitalization rates and mortality within 12 months after LVAD implantation were compared between 83 patients who received medical therapy including an angiotensin receptor neprilysin inhibitor (ARNI) and 83 patients who did not receive an ARNI.
Results
The overall use of heart failure medication after 12 months was high (prescription: beta-blockers 85%, angiotensin inhibiting drugs 90% [angiotensin-converting-enzyme inhibitors 30%, angiotensin receptor blockers 23%, ARNI 37%], mineralocorticoid receptor antagonists 80%). No serious drug-related adverse events occurred. The conditional one-year survival in the group with an ARNI was 97% (95% CI: 94-100%) compared to 88% in the group without an ARNI (95% CI: 80-96%); p=0.06.
Conclusions
Contemporary heart failure therapy is safe in LVAD patients. No increase in serious adverse events was seen in patients receiving an ARNI. No significant difference in the conditional one-year survival was seen between the ARNI group and the non-ARNI group.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 18 Jun 2021; epub ahead of print
Schnettler JK, Roehrich L, Just IA, Pergantis P, ... Potapov E, Schoenrath F
J Card Fail: 18 Jun 2021; epub ahead of print | PMID: 34157393
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Abstract

Combination Biomarkers for Risk Stratification in Patients with Chronic Heart Failure Biomarkers Prognostication in HF.

Feng Z, Akinrimisi OP, Gornbein JA, Truong QA, ... Singh JP, Ajijola O
Background
Current guidelines recommend measuring natriuretic peptide biomarkers to establish prognosis in patients with chronic heart failure with reduced ejection fraction (HFrEF). We assessed whether a combination biomarkers approach improve prognostication in stable HFrEF patients.
Methods
An observational cohort study recruited 202 stable HFrEF patients at a single center, tertiary care hospital undergoing elective cardiac resynchronization therapy device placement from 2013 to 2015. Twenty-four biomarkers were analyzed individually and in combination using Cox proportion hazard regression model for major adverse cardiac event (MACE) (death, cardiac transplant, LVAD placement) and MACE plus HF hospitalizations.
Results
The single best biomarker for predicting MACE is peripheral mid-regional pro-adrenomedullin (MR-proADM) (C statistic=0.771±0.045) compared to current guideline recommended N-terminal pro b-type natriuretic peptide (NT-proBNP) (C=0.668±0.046). The best combined biomarkers for predicting MACE are blood urea nitrogen (BUN), coronary sinus C-reactive protein (CRP), peripheral MR-proANP and peripheral sST2 (C=0.767 ± 0.036).
Conclusion
In this observational cohort, the combined biomarkers (BUN, CRP, MR-proANP and sST2) or the single biomarker (MR-proADM) was superior to NT-proBNP, the current guideline recommended biomarker in predicting cardiovascular outcomes in HFrEF patients. Larger studies are needed to validate these findings and examine whether single or combined biomarkers improve HFrEF prognostication.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 17 Jun 2021; epub ahead of print
Feng Z, Akinrimisi OP, Gornbein JA, Truong QA, ... Singh JP, Ajijola O
J Card Fail: 17 Jun 2021; epub ahead of print | PMID: 34153460
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Abstract

Chronic Intravenous Inotropic Support as Palliative Therapy and Bridge Therapy for Advanced Heart Failure Patients: A Single-Center Experience.

Rao A, Anderson KM, Mohammed S, Hofmeyer M, ... Najjar SS, Groninger H
Background
Many patients with ACC/AHA Stage D (advanced) HF are discharged home on chronic intravenous inotropic support (CIIS) as bridge to surgical therapy or as palliative therapy. This study analyzed the clinical trajectory of patients with advanced heart failure (HF) on home CIIS.
Methods
We conducted a single-institution, retrospective cohort study of patients on CIIS between 2010 and 2016 (n=373), stratified by indication for initiation of inotropic support. Study outcomes were time from initiation of CIIS to cessation of therapy, time to death for patients who did not receive surgical therapy, and rates of involvement of palliative care.
Results
Overall, patients received CIIS therapy for an average of 5.9 months (SD 7.3). Patients on CIIS as palliative therapy died an average of 6.2 months (SD 6.6) from the time of initiation of CIIS, and those on CIIS as bridge therapy who did not ultimately receive surgical therapy died after an average of 8.6 months (SD 9.3). Patients who received CIIS as bridge therapy were significantly less likely to receive palliative care consultation than those on inotropes as palliative therapy, whether or not they underwent surgery.
Conclusions
In this large cohort of patients with advanced HF, patients who on CIIS as palliative therapy survived 6.2 months, on average, with wide variation between patients. Patients who were on CIIS as bridge therapy but did not ultimately receive surgical therapy received less palliative care despite the high mortality in this sub-group.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 17 Jun 2021; epub ahead of print
Rao A, Anderson KM, Mohammed S, Hofmeyer M, ... Najjar SS, Groninger H
J Card Fail: 17 Jun 2021; epub ahead of print | PMID: 34153459
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Abstract

Older Patients with Acute Decompensated Heart Failure Who Live Alone: An Analysis from the REHAB-HF Trial: Patients with Acute Decompensated Heart Failure Living Alone.

Warraich HJ, Kitzman DW, Nelson MB, Mentz RJ, ... Lev Y, Whellan DJ
Background
We assessed the prevalence and clinical characteristics of patients with acute decompensated heart failure (ADHF) who live alone and how they were different from patients who lived with someone else.
Methods
We analyzed patients in the REHAB-HF Trial. Patients were ≥60 years with preserved or reduced ejection fraction who were hospitalized with ADHF.
Results
Of 202 patients, 67 (33.2%) lived alone. Patients who lived alone had a mean age of 72.4±7.8 years, 64% (n=43) of whom were female, 52% (n=35) were non-white and had a mean 6.1±5.5 comorbidities. Patients living alone were largely similar in baseline characteristics, comorbid burden and prescribed medications to patients living with someone else. However, patients living alone were more likely to be female than patients living with someone else (63% [n=43] vs. 49% [n=66], p=0.04). Patients living alone had severe impairments in physical function and QoL. Cognitive dysfunction was present in 81% of those living alone. However, after adjusting for sex, no differences in physical function, depression, cognitive dysfunction or QoL were noted between patients who lived alone or those who lived with someone else.
Conclusions
In this diverse population of older ADHF patients, 33% lived alone (versus 26% in the general population). Those living alone were more often female, non-white, and had >6 comorbidities. Treatment strategies for older ADHF patients should consider the potential impact of social determinants.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 16 Jun 2021; epub ahead of print
Warraich HJ, Kitzman DW, Nelson MB, Mentz RJ, ... Lev Y, Whellan DJ
J Card Fail: 16 Jun 2021; epub ahead of print | PMID: 34147611
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Abstract

Patient Referral Practices to Advanced Heart Failure Centers.

Herr JJ, Ravichandran A, Sheikh FH, Lala A, ... D\'Souza B, IDEAL-HF investigators
Background
AHF therapies improve survival in a growing population of Stage D HF patients. Successful implementation of these therapies is dependent upon timely and appropriate referrals to AHF centers.
Methods
We performed a retrospective analysis of patients referred to 9 AHF centers for evaluation for AHF therapies. Patient demographics, referring provider characteristics, referral circumstances, and evaluation outcomes were collected.
Results
Majority of referrals (N=515) were male (73.4%), with a majority of those in the advanced disease state: very low LVEF <20% in 51.5%, 59.4% inpatient, and high risk INTERMACS profiles (74.5% profile 1-3). HF cardiologists (49.1%) were the most common originating referral source; least common (4.9%) were electrophysiologists. Common clinical triggers for referral included worsening heart failure (30.0%), inotrope dependence (19.6%), hospitalization (19.4%) and cardiogenic shock (17.8%). Most commonly, AHF therapies were not offered due to patients being too sick (38.0 - 45.1%) or psychosocial reasons (20.3 - 28.6%). Compared to non-HF cardiologists, patients referred by HF cardiologists were offered an AHF therapy more often (66.8% vs 58.4% p=0.0489). Of those not offered any AHF therapy, 28.4% received home inotropic therapy and 14.5% were referred to hospice.
Conclusions
In this multicenter review of AHF referrals, HF cardiologists referred the most patients despite being a relatively small proportion of the overall clinician population. Late referral was prevalent in this high-risk patient population and correlates with worsened outcomes, suggesting a significant need for broad clinician education regarding the benefits, triggers and appropriate timing of referral to AHF centers for optimal patient outcomes.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 15 Jun 2021; epub ahead of print
Herr JJ, Ravichandran A, Sheikh FH, Lala A, ... D'Souza B, IDEAL-HF investigators
J Card Fail: 15 Jun 2021; epub ahead of print | PMID: 34146684
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Abstract

Racial and Ethnic Disparities Persist in the Current Era of Pediatric Heart Transplantation.

Amdani S, Bhimani SA, Boyle G, Liu W, ... Saarel E, Hsich E
Background
Older studies demonstrated that children in the U.S. from racial and ethnic minorities have inferior waitlist and post-heart transplant (HT) outcomes. Whether these disparities still exist in the contemporary era of increased ventricular assist device utilization remains unknown.
Methods
All children (age <18 years) in the SRTR database listed for HT from December 2011 to February 2019 were included and separated into 5 race/ethnicities: Caucasian, African American, Hispanic, Asian and Other. Differences in clinical characteristics and survival amongst children of different racial/ethnic groups were compared at listing and at HT.
Results
The waitlist cohort consisted of 2134 (52.2%) Caucasian, 840 (20.5%) African American, 808 (19.8%) Hispanic, 161 (3.9%) Asian, and 146 children of Other races (3.6%). At listing, Asian children mostly had cardiomyopathy (70.8%) while Caucasian children had congenital heart disease (58.7%). African American children were most likely to be listed Status 1A, have renal dysfunction and hypoalbuminemia at listing. African American and Hispanic children were most likely to be on Medicaid. On multivariable analysis, only African American children were at increased risk for waitlist mortality compared to Caucasian children (aHR = 1.25; p = 0.029). Post-HT, there were no disparities in early and mid-term graft survival among groups, however, African American children had increased number of rejection episodes compared to Caucasian and Hispanic children.
Conclusion
African American children continue to experience increased waitlist mortality and have increased rejection episodes post-HT. Studies exploring barriers to healthcare access and implicit bias as reasons for these disparities need to be explored.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 13 Jun 2021; epub ahead of print
Amdani S, Bhimani SA, Boyle G, Liu W, ... Saarel E, Hsich E
J Card Fail: 13 Jun 2021; epub ahead of print | PMID: 34139364
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Impact:
Abstract

Active BNP Measured by Mass Spectrometry and Response to Sacubitril/Valsartan: BNP by MS and Response to Sacubitril/Valsartan.

Dillon EM, Wei SD, Gupta DK, Nian H, ... Stevenson LW, Brown NJ
Background
B-type natriuretic peptide (BNP) immunoassays (ia) do not differentiate active and inactive forms. Inactive NT-proBNP is used to track heart failure (HF) during treatment with sacubitril/valsartan, which inhibits BNP degradation. Mass spectrometry (MS) may better assess effects of HF treatment on biologically active BNP1-32.
Methods and results
We developed a MS assay with immediate protease inhibition to quantify BNP1-32 over a linear range, using labeled recombinant BNP standard. In four healthy volunteers, BNP1-32 by MS (BNPMS) rose from below the 5 pg/ml detection limit to 228 pg/mL after nesiritide. In HF patients, BNPMS was measured in parallel with BNP and NT-proBNP immunoassays before and during sacubitril/valsartan treatment. BNPMS was 4.4-fold lower than BNPia in patients with HF. Among patients not taking sacubitril/valsartan and without ESRD, BNPMS correlated with BNPia (rs=0.77, p<0.001) and NT-proBNP (rs=0.74, p<0.001). After median 8 weeks on sacubitril/valsartan, active BNPMS levels decreased by 50% (IQR -98.3% to 41.7%, N=22, p=0.048) and correlated with NT-proBNP (rs=0.64, p<0.001), but not with BNPia (rs=0.46, p=0.057).
Conclusions
Active BNP measured by MS accounts for only a small amount of BNP measured by immunoassays. Although decreased BNP production was anticipated to be masked by inhibition of degradation, levels of active BNP decreased during chronic sacubitril/valsartan treatment.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 12 Jun 2021; epub ahead of print
Dillon EM, Wei SD, Gupta DK, Nian H, ... Stevenson LW, Brown NJ
J Card Fail: 12 Jun 2021; epub ahead of print | PMID: 34133968
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Impact:
Abstract

Drugs of Abuse and Heart Failure.

Grubb AF, Greene SJ, Fudim M, Dewald T, Mentz RJ
Substance use is common among those with heart failure (HF) and is associated with worse clinical outcomes. Alcohol, tobacco, cannabis, and cocaine are commonly abused substances that can contribute to the development and worsening of HF. Heavy alcohol consumption can lead to dilated cardiomyopathy while moderate intake may reduce incident HF. Tobacco increases the risk of HF through coronary artery disease (CAD) and CAD independent mechanisms. Continued smoking worsens outcomes for those with HF and cessation is associated with improved risk of major adverse cardiac events. Cannabis has complex interactions on the cardiovascular system depending on the method of consumption, amount consumed, and content of cannabinoids. Delta-9-tetrahydrocannabinol (THC) can increase sympathetic tone, cause vascular dysfunction, and may increase the risk of MI. Cannabidiol (CBD) is cardioprotective in pre-clinical studies and is a potential therapeutic target. Cocaine increases sympathetic tone and is a potent proarrhythmogenic agent. It increases the risk of MI and can also lead to a dilated cardiomyopathy. Use of beta-blockers in those with HF and cocaine use is likely safe and effective. Future studies are needed to further elucidate the impact of these substances both on the development of HF and their effects on those who have HF.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 12 Jun 2021; epub ahead of print
Grubb AF, Greene SJ, Fudim M, Dewald T, Mentz RJ
J Card Fail: 12 Jun 2021; epub ahead of print | PMID: 34133967
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Impact:
Abstract

Comparison of Soluble ST2, Pentraxin-3, Galectin-3, and High-Sensitivity Troponin T of Cardiovascular Outcomes in Patients With Acute Decompensated Heart Failure.

Yamamoto M, Seo Y, Ishizua T, Nakagawa D, ... Ohte N, Ieda M
Background
Data regarding a direct comparison of soluble suppression of tumorigenesis-2 (sST2), pentraxin 3 (PTX3), galectin-3 (Gal-3), and high-sensitivity troponin T of cardiovascular outcome in patients with heart failure (HF) are lacking.
Methods and results
A total of 616 hospitalized patients with HF were evaluated prospectively. Biomarker data were obtained in the stable predischarge condition. sST2 levels were associated with age, sex, body mass index, inferior vena cava diameter, B-type natriuretic peptide (BNP), PTX3, C-reactive protein, and Gal-3 levels. During follow-up, 174 (28.4%) primary composite end points occurred, including 58 cardiovascular deaths and 116 HF rehospitalizations. sST2 predicted the end point after adjustment for 13 clinical variables (hazard ratio 1.422; 95% confidence interval [CI] 1.064 to 1.895, P = .018). The association between sST2 and the end point was no longer statistically significant after adjustment for BNP (P = .227), except in the subgroup of patients with preserved ejection fraction (hazard ratio 1.925, 95% CI 1.102-3.378, P = .021). Gal-3 and high-sensitivity troponin T predicted the risk for the end point after adjustment for age and sex, but were not significant after adjustment for clinical variables. The prognostic value of PTX3 was not observed (age and sex adjusted, P = .066).
Conclusions
This study did not show significant additional value of biomarkers to BNP for risk stratification, except sST2 in patients with preserved ejection fraction.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 11 Jun 2021; epub ahead of print
Yamamoto M, Seo Y, Ishizua T, Nakagawa D, ... Ohte N, Ieda M
J Card Fail: 11 Jun 2021; epub ahead of print | PMID: 34129951
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Impact:
Abstract

Clinical Utility of Overlap Time for Incomplete Relaxation to Predict Cardiac Events in Heart Failure.

Kusunose K, Arase M, Zheng R, Hirata Y, ... Wakatsuki T, Sata M
Background
The overlap time of transmitral flow can be a novel marker of subclinical left ventricular dysfunction for predicting adverse events in heart failure (HF). We aimed to (1) investigate the role of overlap time of the E-A wave in association with clinical parameters and (2) evaluate whether the overlap time could add prognostic information with respect to other conventional clinical prognosticators in HF.
Methods
We prospectively evaluated 153 patients hospitalized with HF (mean age 68 ± 15 years; 63% male). The primary endpoint was readmission following HF or cardiac death.
Results
During a median period of 25 months, 43 patients were readmitted or died. Overlap time appeared to be associated with worse outcomes. After adjustment for readmission scores and ratios of diastolic filling period and cardiac cycle length in a Cox proportional-hazards model, overlap time was associated with event-free survival, independent of elevated left atrial pressure based on guidelines. When overlap time was added to the model based on clinical variables and elevated left atrial pressure, the C-statistic significantly improved from 0.70 (95% CI: 0.63-0.77) to 0.77 (95% CI: 0.69-0.83, compared) (P = 0.035).
Conclusion
This preliminary study suggested that prolonged overlap time may have potential for predicting readmission and cardiac mortality risk assessment in patients with HF.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 11 Jun 2021; epub ahead of print
Kusunose K, Arase M, Zheng R, Hirata Y, ... Wakatsuki T, Sata M
J Card Fail: 11 Jun 2021; epub ahead of print | PMID: 34129950
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Impact:
Abstract

Catabolic/Anabolic Imbalance Is Accompanied by Changes of Left Ventricular Steroid Nuclear Receptor Expression in Tachycardia-Induced Systolic Heart Failure in Male Pigs.

Zacharski M, Tomaszek A, Kiczak L, Ugorski M, ... Janiszewski A, Ponikowski P
Background
Steroid hormones play an important role in heart failure (HF) pathogenesis, and clinical data have revealed disordered steroidogenesis in male patients with HF. However, there is still a lack of studies on steroid hormones and their receptors during HF progression. Therefore, a porcine model of tachycardia-induced cardiomyopathy corresponding to HF was used to assess steroid hormone concentrations in serum and their nuclear receptor levels in heart tissue during the consecutive stages of HF.
Methods and results
Male pigs underwent right ventricular pacing and developed a clinical picture of mild, moderate, or severe HF. Serum concentrations of dehydroepiandrosterone, testosterone, dihydrotestosterone, estradiol, aldosterone, and cortisol were assessed by enzyme-linked immunosorbent assay. Androgen receptor, estrogen receptor alpha, mineralocorticoid receptor, and glucocorticoid receptor messenger RNA levels in the left ventricle were determined by qPCR.The androgen level decreased in moderate and severe HF animals, while the corticosteroid level increased. The estradiol concentration remained stable. The quantitative real-time polymerase chain reaction revealed the downregulation of androgen receptor in consecutive stages of HF and increased expression of mineralocorticoid receptor messenger RNA under these conditions.
Conclusions
In the HF pig model, deteriorated catabolic/anabolic balance, manifested by upregulation of aldosterone and cortisol and downregulation of androgen signaling on the ligand level, was augmented by changes in steroid hormone receptor expression in the heart tissue.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 May 2021; 27:682-692
Zacharski M, Tomaszek A, Kiczak L, Ugorski M, ... Janiszewski A, Ponikowski P
J Card Fail: 30 May 2021; 27:682-692 | PMID: 33450412
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Impact:
Abstract

Assessment of Myocardial Fibrosis Using Two-Dimensional and Three-Dimensional Speckle Tracking Echocardiography in Dilated Cardiomyopathy With Advanced Heart Failure.

Wang J, Zhang Y, Zhang L, Tian F, ... Li Y, Xie M
Background
This study aimed to depict strain parameters derived from 2-dimensional (2D)- and 3-dimensional (3D) speckle tracking echocardiography and to explore which may best reflect myocardial fibrosis (MF) in dilated cardiomyopathy with advanced heart failure by comparing with histologic fibrosis.
Methods and results
We analyzed 75 patients with dilated cardiomyopathy with advanced heart failure who underwent echocardiographic examination before heart transplantation. Strain parameters derived from 2D- and 3D speckle tracking echocardiography were as follows: left ventricular global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS) and tangential strain (TS). The degree of MF was quantified using Masson\'s staining in left ventricular myocardial samples obtained from all patients. Seventy-five patients were divided into 3 groups according to the tertiles of histologic MF (mild, moderate, and severe MF groups). Patients with severe MF had lower 3DGLS, 3DGRS, 3DTS, and 2DGLS than those with mild and moderate MF. MF strongly correlated with 3DGLS (r = 0.72, P < .001), weakly with 3DGRS (r = -0.39, P = .001), 3DGCS (r = 0.30, P = .009), 3DTS (r = 0.47, P < .001), and 2DGLS (r = 0.44, P < .001), but did not correlate with 2DGCS and 2DGRS. Receiver operating characteristic analysis revealed that the area under the curve of 3DGLS for detecting severe MF was significantly larger than that of other strain parameters (0.86 vs 0.59-0.70, P < .05 for all). The multivariate linear regression models using 3DGLS (R2 = 0.76; Akaike information criterion = 331) was found to be a more accurate indicator to predict MF than that with 3DTS (R2 = 0.65, Akaike information criterion = 354) and 2DGLS (R2 = 0.66, Akaike information criterion = 352).
Conclusions
Three-dimensional GLS may be an optimal surrogate marker for reflecting MF in patients with dilated cardiomyopathy with advanced heart failure.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 May 2021; 27:651-661
Wang J, Zhang Y, Zhang L, Tian F, ... Li Y, Xie M
J Card Fail: 30 May 2021; 27:651-661 | PMID: 33454418
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Impact:
Abstract

Interleukin-6 and Outcomes in Acute Heart Failure: An ASCEND-HF Substudy.

Perez AL, Grodin JL, Chaikijurajai T, Wu Y, ... Starling RC, Tang WHW
Background
The inflammatory cytokine IL-6 has been previously implicated in the pathophysiology of acute decompensated heart failure (HF). Prior observations in acute HF patients have suggested that IL-6 may be associated with outcomes and modulated by nesiritide. We aimed to evaluate the associations between serial IL-6 measurements, mortality and rehospitalization in acute HF.
Methods and results
We analyzed the associations between IL-6 in acute HF, readmission, and mortality (30 and 180 days) using a cohort of 883 hospitalized patients from the ASCEND-HF trial (nesiritide vs placebo). Plasma IL-6 was measured at randomization (baseline), 48-72 hours, and 30 days. The median IL-6 was highest at baseline (14.1 pg/mL) and decreased at subsequent time points (7.6 pg/mL at 30 days). In a univariable Cox regression analysis, the baseline IL-6 was associated with 30- and 180-day mortality (hazard ratio per log 1.74, 95% confidence interval 1.09-2.78, P = .021; hazard ratio 3.23, confidence interval 1.18-8.86, P = .022, respectively). However, there was no association after multivariable adjustment. IL-6 at 48-72 hours was found to be independently associated with 30-day mortality (hazard ratio 8.2, confidence interval 1.2-57.5, P= .03), but not 180-day mortality in multivariable analysis that included the ASCEND-HF risk model and amino terminal pro-B-type natriuretic peptide as covariates. In comparison with placebo, nesiritide therapy was not associated with differences in serial IL-6 levels.
Conclusions
Although elevated IL-6 levels were associated with higher all-cause mortality in acute HF, no independent association with this outcome was identified at baseline or 30-day measurements. In contrast with prior reports, we did not observe any impact of nesiritide over placebo on serial IL-6 levels.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 May 2021; 27:670-676
Perez AL, Grodin JL, Chaikijurajai T, Wu Y, ... Starling RC, Tang WHW
J Card Fail: 30 May 2021; 27:670-676 | PMID: 33497809
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Impact:
Abstract

Phenotyping of Stable Left Ventricular Assist Device Patients Using Noninvasive Pump Flow Responses to Acute Loading Transients.

Jain P, Adji A, Emmanuel S, Robson D, ... Macdonald PS, Hayward CS
Background
Although it has been established that continuous flow left ventricular assist devices are sensitive to loading conditions, the effect of acute load and postural changes on pump flow have not been explored systematically.
Methods and results
Fifteen stable outpatients were studied. Patients sequentially transitioned from the seated position to supine, passive leg raise, and standing with transition effects documented. A modified Valsalva maneuver, consisting of a forced expiration with an open glottis, was performed in each position. A sustained, 2-handed handgrip was performed in the supine position. The pump flow waveform was recorded continuously and left ventricular end-diastolic diameter measured during each stage using transthoracic echocardiography. Transitioning from seated to supine posture produced a significant increase in the flow and the ventricular end-diastolic diameter, consistent with an increased preload. The transition from supine to standing produced a transient increase in the mean flow and decreased the flow pulsatility index. At steady state, these changes were reversed with a decrease in the mean and trough flow and increased pulsatility index, consistent with venous redistribution and possible baroreflex compensation. Four distinct patterns of standing-induced flow waveform effects were identified, reflecting varying preload, afterload, and individual compensatory effects. A sustained handgrip produced a significant decrease in flow and increase in flow pulsatility across all patients, reflecting an increased afterload pressure. A modified Valsalva maneuver produced a decrease in the flow pulsatility while seated, supine, and standing, but not during leg raise. Five patterns of pulsatility effect during Valsalva were observed: (1) minimal change, (2) pulsatility recovery, (3) rapid flatline, (4) slow flatline with delayed flow recovery, and (5) primary suction.
Conclusions
Acute disturbances in loading conditions produce heterogeneous pump flow responses reflecting their complex interactions with pump and ventricular function as well as reflex compensatory mechanisms. Differences in responses and individual variabilities have significant implications for automated pump control algorithms.

Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.

J Card Fail: 30 May 2021; 27:642-650
Jain P, Adji A, Emmanuel S, Robson D, ... Macdonald PS, Hayward CS
J Card Fail: 30 May 2021; 27:642-650 | PMID: 33497807
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Impact:
Abstract

Exercise Intolerance in Heart Failure With Preserved Ejection Fraction: Arterial Stiffness and Aabnormal Left Ventricular Hemodynamic Responses During Exercise.

Zern EK, Ho JE, Panah LG, Lau ES, ... Nayor M, Lewis GD
Background
Arterial stiffness is thought to contribute to the pathophysiology of heart failure with preserved ejection fraction (HFpEF). We sought to examine arterial stiffness in HFpEF and hypertension and investigate associations of arterial and left ventricular hemodynamic responses to exercise.
Methods and results
A total of 385 symptomatic individuals with an EF of ≥50% underwent upright cardiopulmonary exercise testing with invasive hemodynamic assessment of arterial stiffness and load (aortic augmentation pressure, augmentation index, systemic vascular resistance index, total arterial compliance index, effective arterial elastance index, and pulse pressure amplification) at rest and during incremental exercise. An abnormal hemodynamic response to exercise was defined as a steep increase in pulmonary capillary wedge pressure relative to cardiac output (∆PCWP/∆CO > 2 mm Hg/L/min). We compared rest and exercise measures between HFpEF and hypertension in multivariable analyses. Among 188 participants with HFpEF (mean age 61 ± 13 years, 56% women), resting arterial stiffness parameters were worse compared with 94 hypertensive participants (mean age 55 ± 15 years, 52% women); these differences were accentuated during exercise in HFpEF (all P ≤ .0001). Among all participants, exercise measures of arterial stiffness correlated with worse ∆PCWP/∆CO. Specifically, a 1 standard deviation higher exercise augmentation pressure was associated with 2.15-fold greater odds of abnormal LV hemodynamic response (95% confidence interval 1.52-3.05; P < .001). Further, exercise measures of systemic vascular resistance index, elastance index, and pulse pressure amplification correlated with a lower peak oxygen consumption.
Conclusions
Exercise accentuates the increased arterial stiffness found in HFpEF, which in turn correlates with left ventricular hemodynamic responses. Unfavorable ventricular-vascular interactions during exercise in HFpEF may contribute to exertional intolerance and inform future therapeutic interventions.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 May 2021; 27:625-634
Zern EK, Ho JE, Panah LG, Lau ES, ... Nayor M, Lewis GD
J Card Fail: 30 May 2021; 27:625-634 | PMID: 33647476
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Impact:
Abstract

Increased Aortic Stiffness Is Associated With Higher Rates of Stroke, Gastrointestinal Bleeding and Pump Thrombosis in Patients With a Continuous Flow Left Ventricular Assist Device.

Rosenblum H, Pinsino A, Zuver A, Javaid A, ... Colombo PC, Stöhr EJ
Background
In the general population, increased aortic stiffness is associated with an increased risk of cardiovascular events. Previous studies have demonstrated an increase in aortic stiffness in patients with a continuous flow left ventricular assist device (CF-LVAD). However, the association between aortic stiffness and common adverse events is unknown.
Methods and results
Forty patients with a HeartMate II (HMII) (51 $ 11 years; 20% female; 25% ischemic) implanted between January 2011 and September 2017 were included. Two-dimensional transthoracic echocardiograms of the ascending aorta, obtained before HMII placement and early after heart transplant, were analyzed to calculate the aortic stiffness index (AO-SI). The study cohort was divided into patients who had an increased vs decreased AO-SI after LVAD support. A composite outcome of gastrointestinal bleeding, stroke, and pump thrombosis was defined as the primary end point and compared between the groups. While median AO-SI increased significantly after HMII support (AO-SI 4.4-6.5, P = .012), 16 patients had a lower AO-SI. Patients with increased (n = 24) AO-SI had a significantly higher rate of the composite end point (58% vs 12%, odds ratio 9.8, P < .01). Similarly, those with increased AO-SI tended to be on LVAD support for a longer duration, had higher LVAD speed and reduced use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.
Conclusions
Increased aortic stiffness in patients with a HMII is associated with a significantly higher rates of adverse events. Further studies are warranted to determine the causality between aortic stiffness and adverse events, as well as the effect of neurohormonal modulation on the conduit vasculature in patients with a CF-LVAD.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 May 2021; 27:696-699
Rosenblum H, Pinsino A, Zuver A, Javaid A, ... Colombo PC, Stöhr EJ
J Card Fail: 30 May 2021; 27:696-699 | PMID: 33639317
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Impact:
Abstract

The Cost-Effectiveness of Palliative Care: Insights from the PAL-HF Trial.

Kaufman BG, Granger BB, Sun JL, Sanders G, ... O\'Connor C, Mentz RJ
Background
In a randomized control trial, Palliative Care in Heart Failure (PAL-HF) improved heart failure-related quality of life, though cost-effectiveness remains unknown. The aim of this study was to evaluate the cost-effectiveness of the PAL-HF trial, which provided outpatient palliative care to patients with advanced heart failure.
Methods and results
Outcomes for usual care and PAL-HF strategies were compared using a Markov cohort model over 36 months from a payer perspective. The model parameters were informed by PAL-HF trial data and supplemented with meta-analyses and Medicare administrative data. Outcomes included hospitalization, place of death, Medicare expenditures, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios. Simulated mortality rates were the same for PAL-HF and usual care cohorts, at 89.7% at 36 months. In the base case analysis, the PAL-HF intervention resulted in an incremental gain of 0.03 QALYs and an incremental cost of $964 per patient for an incremental cost-effectiveness ratio of $29,041 per QALY. In 1-way sensitivity analyses, an intervention cost of up to $140 per month is cost effective at $50,000 per QALY. Of 1000 simulations, the PC intervention had a 66.1% probability of being cost effective at a $50,000 willingness-to-pay threshold assuming no decrease in hospitalization. In a scenario analysis, PAL-HF decreased payer spending through reductions in noncardiovascular hospitalizations.
Conclusions
These results from this single-center trial are encouraging that palliative care for advanced heart failure is an economically attractive intervention. Confirmation of these findings in larger multicenter trials will be an important part of developing the evidence to support more widespread implementation of the PAL-HF palliative care intervention.

Published by Elsevier Inc.

J Card Fail: 30 May 2021; 27:662-669
Kaufman BG, Granger BB, Sun JL, Sanders G, ... O'Connor C, Mentz RJ
J Card Fail: 30 May 2021; 27:662-669 | PMID: 33731305
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Impact:
Abstract

Non-Concordance between Patient and Clinician Estimates of Prognosis in Advanced Heart Failure.

Gelfman LP, Mather H, McKendrick K, Wong AY, ... Morrison RS, Goldstein NE
Importance
Despite efforts to enhance serious illness communication, patients with advanced heart failure (HF) lack prognostic understanding.
Objectives
To determine rate of concordance between HF patients\' estimation of their prognosis and their physician\'s estimate of the patient\'s prognosis, and to compare patient characteristics associated with concordance.
Design
Cross-sectional analysis of a cluster randomized controlled trial with 24-month follow-up and analysis completed on 09/01/2020. Patients were enrolled in inpatient and outpatient settings between September 2011 to February 2016 and data collection continued until the last quarter of 2017.
Setting
Six teaching hospitals in the U.S.
Participants
Patients with advanced HF and implantable cardioverter defibrillators (ICDs) at high risk of death. Of 537 patients in the parent study, 407 had complete data for this analysis.
Intervention
A multi-component communication intervention on conversations between HF clinicians and their patients regarding ICD deactivation and advance care planning.
Main outcome(s) and measure(s)
Patient self-report of prognosis and physician response to the \"surprise question\" of 12-month prognosis. Patient-physician prognostic concordance (PPPC) measured in percentage agreement and kappa. Bivariate analyses of characteristics of patients with and without PPPC.
Results
Among 407 patients (mean age 62.1 years, 29.5% female, 42.4% non-white), 300 (73.7%) dyads had non-PPPC; of which 252 (84.0%) reported a prognosis >1 year when their physician estimated <1 year. Only 107 (26.3%) had PPPC with prognosis of ≤ 1 year (n=20 patients) or > 1 year (n=87 patients); (Κ = -0.20, p = 1.0). Of those with physician estimated prognosis of < 1 year, non-PPPC was more likely among patients with lower symptom burden- number and severity (both p ≤.001), without completed advance directive (p=.001). Among those with physician prognosis estimate > 1 year, no patient characteristic was associated with PPPC or non-PPPC.

Conclusions:
and relevance
Non-PPPC between HF patients and their physicians is high. HF patients are more optimistic than clinicians in estimating life expectancy. These data demonstrate there are opportunities to improve the quality of prognosis disclosure between patients with advanced HF and their physicians. Interventions to improve PPPC might include serious illness communication training.

Published by Elsevier Inc.

J Card Fail: 30 May 2021; 27:700-705
Gelfman LP, Mather H, McKendrick K, Wong AY, ... Morrison RS, Goldstein NE
J Card Fail: 30 May 2021; 27:700-705 | PMID: 34088381
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Impact:
Abstract

Phenotype/Genotype Relationship in Left Ventricular Noncompaction: Ion Channel Gene Mutations Are Associated With Preserved Left Ventricular Systolic Function and Biventricular Noncompaction: Phenotype/Genotype of Noncompaction.

Cambon-Viala M, Gerard H, Nguyen K, Richard P, ... Charron P, Habib G
Background
Few data exist concerning genotype-phenotype relationships in left ventricular noncompaction (LVNC).
Methods and results
From a multicenter French Registry, we report the genetic and clinical spectrum of 95 patients with LVNC, and their genotype-phenotype relationship. Among the 95 LVNC, 45 had at least 1 mutation, including 14 cases of mutation in ion channel genes. In a complementary analysis including 16 additional patients with ion channel gene mutations, for a total of 30 patients with ion channel gene mutation, we found that those patients had higher median LV ejection fraction (60% vs 40%; P < .001) and more biventricular noncompaction (53.1% vs 18.5%; P < .001) than the 81 other patients with LVNC. Among them, both the 19 patients with an HCN4 mutation and the 11 patients with an RYR2 mutation presented with a higher LV ejection fraction and more frequent biventricular noncompaction than the 81 patients with LVNC but with no mutation in the ion channel gene, but only patients with HCN4 mutation presented with a lower heart rate.
Conclusions
Ion channel gene mutations should be searched systematically in patients with LVNC associated with either bradycardia or biventricular noncompaction, particularly when LV systolic function is preserved. Identifying causative mutations is of utmost importance for genetic counselling of at-risk relatives of patients affected by LVNC.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 May 2021; 27:677-681
Cambon-Viala M, Gerard H, Nguyen K, Richard P, ... Charron P, Habib G
J Card Fail: 30 May 2021; 27:677-681 | PMID: 34088380
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Impact:
Abstract

Relationships Between Objectively Measured Physical Activity, Exercise Capacity, and Quality of Life in Older Patients With Obese Heart Failure and Preserved Ejection Fraction.

German CA, Brubaker PH, Nelson MB, Fanning J, Ye F, Kitzman DW
Background
The relationship between physical activity (PA), exercise capacity, and quality of life (QOL) in obese heart failure with preserved ejection fraction is poorly understood.
Methods and results
This was an ancillary study to a clinical trial. Accelerometers were used to measure light PA, moderate to vigorous PA, total PA, PA energy expenditure, and steps. Peak VO2, exercise time, and 6-minute walk distance, as well as QOL measures were obtained. Pearson correlations were performed to examine relationships between PA, exercise capacity, and QOL. Patients (n = 58) were 68.0 ± 5.7 years old, 78% female, 59% White, and obese (body mass index 39.1 ± 6.1 kg/m2). Patients had low levels of objectively measured PA as well as decreased exercise capacity and poor QOL. Light PA (r = 0.32, P = .014) and steps per day (r = 0.30, P = .022) were modestly correlated with peak VO2. All PA variables were modestly correlated with exercise time (r = 0.33-0.49, all P < .02) and 6-minute walk distance (r = 0.25-0.48, all P < .01). None of the PA variables were correlated with QOL.
Conclusions
PA variables were modestly correlated with measures of exercise capacity and were not significantly correlated with QOL. Our findings indicate that PA, exercise capacity, and QOL assess different aspects of the patient experience in older obese patients with heart failure with preserved ejection fraction.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 May 2021; 27:635-641
German CA, Brubaker PH, Nelson MB, Fanning J, Ye F, Kitzman DW
J Card Fail: 30 May 2021; 27:635-641 | PMID: 34088379
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Impact:
Abstract

Characteristics of Elderly Patients with Heart Failure and Impact on Activities of Daily Living: A Registry Report from Super-Aged Society.

Obata H, Izumi T, Yamashita M, Mitsuma W, ... Morimoto T, Isobe M
Background
To assess the health care burden of elderly patients with heart failure (HF) in an aging Japanese community-based hospital, we investigated the outcomes of cardiac rehabilitation.
Methods and results
We enrolled all patients with HF aged ≥65 years admitted to 3 hospitals in the Niigata Prefecture. We prospectively collected data on their hospital stays and for 2 years postdischarge. The cohort comprised 617 patients (46.5% men; mean age 84.7 years), 76.2% of whom were aged ≥80 years. Among these patients, 15.6% were nursing home residents, 57.7% required long-term care insurance, only 37.6% could walk unaided at the time of admission, and 70.5% required cardiac rehabilitation; age had no significant rehabilitative effect on the degree of improvement in activities of daily living (ADLs). Two years postdischarge, all-cause mortality, and HF rehospitalization were 41.1% and 38.6%, respectively. The ADL score at discharge was an independent prognostic factor for mortality. The incidence of mortality and rehospitalization was lower in elderly patients with preserved ADLs at discharge.
Conclusions
Elderly patients with HF in our super-aged society were mainly octogenarians who required disease management and personalized care support. Although their ADL scores increased with comprehensive cardiac rehabilitation, improved scores at discharge were closely associated with prognosis.

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

J Card Fail: 27 May 2021; epub ahead of print
Obata H, Izumi T, Yamashita M, Mitsuma W, ... Morimoto T, Isobe M
J Card Fail: 27 May 2021; epub ahead of print | PMID: 34052442
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Impact:
Abstract

Enhanced Recovery After Surgery in Patients Implanted with Left Ventricular Assist Device.

Lindenmuth DM, Chase K, Cheyne C, Wyrobek J, ... Alexis JD, Gosev I
Introduction
We sought to develop and implement a comprehensive enhanced recovery after surgery (ERAS) protocol for patients implanted with a left ventricular assist device (LVAD).
Methods and results
In this article, we describe our approach to the development and phased implementation of the protocol. Additionally, we reviewed prospectively collected data for patients who underwent LVAD implantation at our institution from February 2019 to August 2020. To compare early outcomes in our patients before and after protocol implementation, we dichotomized patients into two 6-month cohorts (the pre-ERAS and ERAS cohorts) separated from each other by 6 months to allow for staff adoption of the protocol. Of the 115 LVAD implants, 38 patients were implanted in the pre-ERAS period and 46 patients in the ERAS period. Preoperatively, the patients` characteristics were similar between the cohorts. Postoperatively, we observed a decrease in bleeding (chest tube output of 1006 vs 647.5 mL, P < .001) and blood transfusions (fresh frozen plasma 31.6% vs 6.7%, P = .04; platelets 42.1% vs 8.7%, P = .001). Opioid prescription at discharge were 5-fold lower with the ERAS approach (P < .01). Furthermore, the number of patients discharged to a rehabilitation facility decreased significantly (20.0% vs 2.4%, P = .02). The index hospitalization length of stay and survival were similar between the groups.
Conclusions
ERAS for patients undergoing LVAD implantation is a novel, evidence-based, interdisciplinary approach to care with multiple potential benefits. In this article, we describe the details of the protocol and early positive changes in clinical outcomes. Further studies are needed to evaluate benefits of an ERAS protocol in an LVAD population.Lay Summary: Enhanced recovery after surgery (ERAS) is the implementation of standardized clinical pathways that ensures the use of best practices and decreased variation in perioperative care. Multidisciplinary teams work together on ERAS, thereby enhancing communication among health care silos. ERAS has been used for more than 30 years by other surgical services and has been shown to lead to a decreased length of stay, fewer complications, lower mortality, fewer readmissions, greater job satisfaction, and lower costs. Our goal was to translate these benefits to the perioperative care of complex patients with a left ventricular assist device. Early results suggest that this goal is possible; we have observed a decrease in transfusions, discharge on opioids, and discharge to a rehabilitation facility.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 25 May 2021; epub ahead of print
Lindenmuth DM, Chase K, Cheyne C, Wyrobek J, ... Alexis JD, Gosev I
J Card Fail: 25 May 2021; epub ahead of print | PMID: 34048920
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Impact:
Abstract

Effects of Neighborhood-level Data on Performance and Algorithmic Equity of a Model That Predicts 30-day Heart Failure Readmissions at an Urban Academic Medical Center.

Weissman GE, Teeple S, Eneanya ND, Hubbard RA, Kangovi S
Background
Socioeconomic data may improve predictions of clinical events. However, owing to structural racism, algorithms may not perform equitably across racial subgroups. Therefore, we sought to compare the predictive performance overall, and by racial subgroup, of commonly used predictor variables for heart failure readmission with and without the area deprivation index (ADI), a neighborhood-level socioeconomic measure.
Methods and results
We conducted a retrospective cohort study of 1316 Philadelphia residents discharged with a primary diagnosis of congestive heart failure from the University of Pennsylvania Health System between April 1, 2015, and March 31, 2017. We trained a regression model to predict the probability of a 30-day readmission using clinical and demographic variables. A second model also included the ADI as a predictor variable. We measured predictive performance with the Brier Score (BS) in a held-out test set. The baseline model had moderate performance overall (BS 0.13, 95% CI 0.13-0.14), and among White (BS 0.12, 95% CI 0.12-0.13) and non-White (BS 0.13, 95% CI 0.13-0.14) patients. Neither performance nor algorithmic equity were significantly changed with the addition of the ADI.
Conclusions
The inclusion of neighborhood-level data may not reliably improve performance or algorithmic equity.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 25 May 2021; epub ahead of print
Weissman GE, Teeple S, Eneanya ND, Hubbard RA, Kangovi S
J Card Fail: 25 May 2021; epub ahead of print | PMID: 34048918
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Impact:
Abstract

Captopril Versus Hydralazine-Isosorbide Dinitrate Vasodilator Protocols in Patients With Acute Decompensated Heart Failure Transitioning From Sodium Nitroprusside.

Amar M, Lam SW, Faulkenberg K, Perez A, Tang WHW, Williams JB
Background
The role of oral vasodilators in the management of acute decompensated heart failure (ADHF) is not clearly defined. We evaluated the use of captopril vs hydralazine-isosorbide dinitrate (H-ISDN) in the transition from sodium nitroprusside (SNP) in patients with ADHF.
Methods and results
A retrospective chart review was performed of 369 consecutive adult patients in the intensive care unit with ADHF and reduced ejection fraction, who received either a captopril or an H-ISDN protocol to transition from SNP. Captopril patients were matched 1:2 to H-ISDN patients, based on serum creatinine and race (Black vs non-Black). Baseline demographics, serum chemistry and use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) were similar in both groups. Time to SNP discontinuation (46.9 vs 40.4 hours, P = 0.11) and length of hospital stay (9.86 vs 7.99 days, P = 0.064) were similar in both groups. Length of hospital stay in the intensive care unit was statistically shorter in the H-ISDN group (4.11 vs 3.96 days, P = 0.038). Fewer H-ISDN protocol patients were discharged on ACEis/ARBs (82.9 % vs 69.9%, P = 0.003) despite similar kidney function at time of discharge (serum creatinine 1.1 vs 1.2, P = 0.113). No difference was observed in rates of readmission (40.7% vs 50%, P = 0.09) or mortality (16.3% vs 17.5 %, P = 0.77) at 1 year postdischarge.
Conclusion
Similar inpatient and 1-year outcomes were observed between patients using H-ISDN vs ACEi when transitioning from SNP, even though fewer H-ISDN protocol patients were discharged taking ACEis/ARBs despite similar kidney function.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 25 May 2021; epub ahead of print
Amar M, Lam SW, Faulkenberg K, Perez A, Tang WHW, Williams JB
J Card Fail: 25 May 2021; epub ahead of print | PMID: 34051349
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Impact:
Abstract

Hepatocyte Growth Factor and Incident Heart Failure Subtypes: The Multi-Ethnic Study of Atherosclerosis (MESA).

Ferraro RA, Ogunmoroti O, Zhao D, Ndumele CE, ... Bielinski SJ, Michos ED
Background
Hepatocyte growth factor (HGF) is a cytokine and marker of cardiovascular disease (CVD) risk. Less is known about HGF and incident heart failure (HF). We examined the association of HGF with incident HF and its subtypes in a multiethnic cohort.
Methods and results
We included 6597 participants of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, free of clinical CVD and HF at baseline, with HGF measured at baseline. Incident hospitalized HF was assessed and adjudicated for HF with preserved ejection fracture (HFpEF) vs HF with reduced ejection fraction (HFrEF). Cox regression models estimated hazard ratios (HR) and 95% confidence intervals (CI) for HF risk by HGF levels, adjusted for socio-demographics, CVD risk factors and N-terminal pro-B-type natriuretic peptide. The mean age was 62 ± 10 years. The median HGF level was 950 pg/mL (interquartile range, 758-1086 pg/mL); 53% were women. Over 14 years (IQR, 11.5-14.7 years), there were 324 cases of HF (133 HFpEF and 157 HFrEF). For the highest HGF tertile compared with lowest, adjusted HRs were 1.59 (95% CI, 1.10-2.31), 1.90 (95% CI, 1.03-3.51), and 1.09 (95% CI, 0.65-1.82) for overall HF, HFpEF, and HFrEF, respectively. For continuous analysis per 1-standard deviation log-transformed HGF, adjusted HRs were 1.22 (95% CI, 1.06-1.41), 1.35 (95% CI, 1.09-1.69), and 1.00 (95% CI, 0.81-1.24) for HF, HFpEF, and HFrEF, respectively.
Conclusions
HGF was independently associated with incident HF. HGF remained significantly associated with HFpEF but not HFrEF upon subtype assessment. Future studies should examine the mechanisms underlying these associations and evaluate whether HGF can be used to improve HF risk prediction or direct therapy.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 25 May 2021; epub ahead of print
Ferraro RA, Ogunmoroti O, Zhao D, Ndumele CE, ... Bielinski SJ, Michos ED
J Card Fail: 25 May 2021; epub ahead of print | PMID: 34051347
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Impact:
Abstract

Clinical Outcome Predictions for the VerICiguaT Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) Trial: VICTORIA Outcomes Model.

Mentz RJ, Mulder H, Mosterd A, Sweitzer NK, ... O\'Connor CM, VICTORIA Study Group
Background
Prediction of outcomes in patients with heart failure (HF) may inform prognosis, clinical decisions regarding treatment selection, and new trial planning. The VICTORIA trial included high-risk patients with HF and reduced ejection fraction and a recent worsening HF event. The study participants had an unusually high event rate despite usage of contemporary guideline-based therapies. To provide generalizable predictive data for a broad population with a recent worsening HF event, we focused on risk prognostication in the placebo group.
Methods
Data from 2524 participants randomized to placebo with chronic HF (New York Heart Association class [NYHA] II-IV) and ejection fraction <45% were studied and backward variable selection was used to create Cox proportional hazards models for clinical endpoints, selecting from 66 candidate predictors. Final model results were produced, accounting for missing data, non-linearities, and interactions with treatment. Optimism-corrected c-indices were calculated using 200 bootstrap samples.
Results
During a median follow-up of 10.4 months, the primary outcome of HF hospitalization or cardiovascular death occurred in 972 (38.5%) patients. Independent predictors of increased risk for the primary endpoint included HF characteristics (longer HF duration and worse NYHA class), medical history (prior myocardial infarction), and laboratory values (higher N-terminal pro-hormone B-type natriuretic peptide, bilirubin, urate; lower chloride and albumin). Optimism-corrected c-indices were 0.68 for the HF hospitalization/cardiovascular death model, 0.68 for HF hospitalization/all-cause death, 0.72 for cardiovascular death, and 0.73 for all-cause death.
Conclusions
Predictive models developed in a large diverse clinical trial with comprehensive clinical and laboratory baseline data-including novel measures-performed well in high-risk HF patients who were receiving excellent guideline-based clinical care.
Clinical trial registration
Clinicaltrials.gov identifier, NCT02861534.
Lay summary
Patients with heart failure may benefit from tools that help clinicians better understand patient\'s risk for future events like hospitalization. Relatively few risk models have been created after worsening of heart failure in a contemporary cohort. We provide insights on risk factors for clinical events from a recent large, global trial of patients with worsening heart failure to help clinicians better understand and communicate prognosis and select treatment options.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 25 May 2021; epub ahead of print
Mentz RJ, Mulder H, Mosterd A, Sweitzer NK, ... O'Connor CM, VICTORIA Study Group
J Card Fail: 25 May 2021; epub ahead of print | PMID: 34216757
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Abstract

Misdiagnosis of Heart Failure: A Systematic Review of the Literature.

Wong CW, Tafuro J, Azam Z, Satchithananda D, ... Mallen C, Kwok CS
Background
Heart failure (HF) is a chronic disease associated with a significant burden to patients, families, and health services. The diagnosis of HF can be easily missed owing to similar symptoms with other conditions especially respiratory diseases.
Methods and results
We conducted a systematic review to determine the rates of HF and cardiomyopathy misdiagnosis and explored the potential causes. The included studies were narratively synthesized. Ten studies were identified including a total of 223,859 patients. There was a lack of definition of HF misdiagnosis in the studies and inconsistent diagnostic criteria were used. The rates of HF misdiagnosis ranged from 16.1% in hospital setting to 68.5% when general practitioner referred patients to specialist setting. The most common cause for misdiagnosis was chronic obstructive pulmonary disease (COPD). One study using a COPD cohort showed that HF was unrecognized in 20.5% of patients and 8.1% had misdiagnosis of HF as COPD. Another study suggests that anemia and chronic kidney disease are associated with an increase in the odds of unrecognized left ventricular systolic dysfunction. Other comorbidities such as obesity, old age, atrial fibrillation, and ischemic heart disease are prevalent in patients with a misdiagnosis of HF.
Conclusions
The misdiagnosis of HF is an unfortunate part of everyday clinical practice that occurs with a variable rate depending on the population studied. HF is frequently misdiagnosed as COPD. More research is needed to better understand the missed opportunities to correctly diagnose HF so that harm to patients can be avoided and effective treatments can be implemented.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 24 May 2021; epub ahead of print
Wong CW, Tafuro J, Azam Z, Satchithananda D, ... Mallen C, Kwok CS
J Card Fail: 24 May 2021; epub ahead of print | PMID: 34048921
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Impact:
Abstract

Aortic Pulsatility Index: A Novel Hemodynamic Variable for Evaluation of Decompensated Heart Failure.

Belkin MN, Kalantari S, Kanelidis AJ, Miller T, ... Kim G, Grinstein J
Background
Right heart catheterization for invasive hemodynamics has shown only modest correlation with clinical outcomes. We designed a novel hemodynamic variable that incorporates ventricular output and filling pressure. We anticipated that the aortic pulsatility index (API) would correlate with clinical outcomes in patients with heart failure.
Methods and results
We retrospectively analyzed consecutive patients undergoing right heart catheterization with milrinone drug study at our institution (February 2013 to November 2019). The API was calculated as (systolic blood pressure - diastolic blood pressure)/pulmonary capillary wedge pressure. The primary outcome was freedom from advanced therapies, defined as the need for inotropes, temporary mechanical circulatory support, a left ventricular assist device, or orthotopic heart transplantation, or death at 30 days. A total of 224 patient encounters, age 57 years (48-66 years; 34% women; 31% ischemic cardiomyopathy) were included. In univariable analysis, lower baseline API was significantly associated with progression to advanced therapies or death at 30-days (odds ratio 0.43, 95% confidence interval 0.30-0.61; P < .001) compared with those on continued medical management. Receiver operator characteristic analysis specified an optimal cutpoint of 1.45 for API. A Kaplan-Meier analysis indicated an association of API with the primary outcome (79% for API ≥ 1.45 vs 48% for API < 1.45). In multivariable analysis, higher API was strongly associated with freedom from advanced therapies or death (odds ratio 0.38, 95% confidence interval 0.22-0.65, P ≤ .001), even when adjusted for baseline characteristics and routine right heart catheterization measurements.
Conclusions
The API is a novel invasive hemodynamic measurement that is associated independently with freedom from advanced therapies or death at 30-day follow-up.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 24 May 2021; epub ahead of print
Belkin MN, Kalantari S, Kanelidis AJ, Miller T, ... Kim G, Grinstein J
J Card Fail: 24 May 2021; epub ahead of print | PMID: 34048919
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Impact:
Abstract

Is There Any Interaction Between Sex and Renal Function Change During Hospital Stay in Patients Hospitalized With Acute Heart Failure?

Julius FEC, VAN Norel MR, Zandijk AJL, Rathwell S, ... Voors AA, Ezekowitz JA
Background
Renal dysfunction is a strong predictor of outcomes in patients with acute heart failure (AHF). However, less is known about how sex may influence the prognostic import of renal function in AHF.
Methods and results
In a post hoc analysis of the ASCEND-HF trial including 5377 patients with AHF (33% female), patients were categorized into 3 groups based on the changes in renal function during their hospital stay. Worsening, stable, and improving renal functions were defined as a ≥20% decrease, a <20% change, and a ≥20% increase in the estimated glomerular filtration rate, respectively. The primary outcome was the composite of 30-day all-cause mortality or HF rehospitalization. The median baseline and discharge estimated glomerular filtration rate were 58.4 and 56.9 mL/min/1.73 m2, respectively. Worsening, stable, and improving renal function was observed in 31.9%, 63.2, and 4.9% of patients, respectively. Worsening renal function was associated with adverse outcomes at 30 days (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.22-1.76). This association existed in both males and females (aHR 1.42 and aHR 1.56, respectively, both P < .01). There was an interaction between renal function changes and sex (P = .025), because improving renal function was associated with better outcomes in men (aHR 0.29, 95% CI 0.13-0.66) as compared with women (aHR 1.18, 95% CI 0.59-2.35). There was no interaction between the ejection fraction and renal function in association with subsequent outcomes.
Conclusions
Irrespective of sex, worsening renal function was associated with poorer outcomes at 30 days in patients with AHF. More studies are warranted to further delineate the possible sex differences in this setting.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 24 May 2021; epub ahead of print
Julius FEC, VAN Norel MR, Zandijk AJL, Rathwell S, ... Voors AA, Ezekowitz JA
J Card Fail: 24 May 2021; epub ahead of print | PMID: 34048917
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Impact:
Abstract

Distribution and Correlates of Incident Heart Failure Risk in South Asian Americans: The MASALA Study.

Shah NS, Agarwal A, Huffman MD, Gupta DK, ... Kandula NR, Khan SS
Background
South Asian Americans experience disproportionately high burden of cardiovascular diseases. Estimating predicted heart failure (HF) risk distribution may facilitate targeted prevention. We estimated the distribution of 10-year predicted risk of incident HF in South Asian Americans and evaluated the associations with social determinants of health and clinical risk factors.
Methods and results
In the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study, we calculated 10-year predicted HF risk using the Pooled Cohort Equations to Prevent Heart Failure multivariable model. Distributions of low (<1%), intermediate (1%-5%), and high (≥5%) HF risk, identified overall and by demographic and clinical characteristics, were compared. We evaluated age- and sex-adjusted associations of demographic characteristics and coronary artery calcium with predicted HF risk category using ordinal logistic regression. In 1159 participants (48% women), with a mean age of 57 ± 9 years, 40% had a low, 37% had an intermediate, and 24% had a high HF risk. Significant differences in HF risk distribution existed across demographic (income, education, birthplace) and clinical (diabetes, hypertension, body mass index, coronary artery calcium) groups (P < .01). Significant associations with high predicted HF risk were observed for a family of income 75,000/year or more (adjusted odds ratio 0.5 [95% confidence interval (CI) 0.4-0.7]), college education (0.6 [95% CI 0.4-0.9]), birthplace in another South Asian country (1.9 [95% CI 1.2-3.2], vs. born in India), and prevalent coronary artery calcium (2.6 [95% CI 1.9-3.6]).
Conclusions
Almost two-thirds of South Asian Americans in the MASALA cohort are at intermediate or high predicted 10-year HF risk, with varying risk across demographic and clinical characteristics.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 24 May 2021; epub ahead of print
Shah NS, Agarwal A, Huffman MD, Gupta DK, ... Kandula NR, Khan SS
J Card Fail: 24 May 2021; epub ahead of print | PMID: 34048916
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Impact:
Abstract

An Interprofessional Collaborative Practice Can Reduce Heart Failure Hospital Readmissions and Costs in an Underserved Population.

White-Williams C, Shirey M, Eagleson R, Clarkson S, Bittner V
Background
Heart failure is a leading cause of hospitalization among adults in the United States. Nurse-led interprofessional clinics have been shown to improve heart failure outcomes in patients with heart failure, specifically decreasing readmission rates. Yet, there is little information on the impact of nurse-led interprofessional collaborative practice within an underserved population with heart failure. Thus, the purpose of this study was to compare the differences in readmission days and cost in patients followed by an interprofessional collaborative practice clinic (both engaged and not engaged) and those who did not establish care with the clinic.
Methods and results
Demographic, clinical, and readmission data were compared among patients with heart failure (59% African American; 72% male; mean age, 49 years) stratified into 3 groups: engaged patients (n = 170), not-engaged patients (n = 103), and not-established patients (n = 111) who had an initial appointment to clinic but did not establish care. Patients with 6 months of data before and after the scheduled clinic visit were included in the study. Differences in baseline characteristics, frequency and length of hospital admissions, and costs were analyzed using analysis of variance, Wilcoxon matched-pairs testing, multivariate analysis of variance, logistic regression, and financial analytics. Overall, the number of inpatient hospital days decreased in the engaged group compared with those in the not-engaged and not-established groups (P < .001). The total cost savings were significantly greater in the engaged group ($1,987,379) (P < .001).
Conclusions
The findings of this study may steer health care providers to incorporate interprofessional collaborative practice into heart failure management with a particular focus on underserved populations.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 12 May 2021; epub ahead of print
White-Williams C, Shirey M, Eagleson R, Clarkson S, Bittner V
J Card Fail: 12 May 2021; epub ahead of print | PMID: 33991685
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Impact:
Abstract

Right Ventricular Pressure-Volume Analysis During Left Ventricular Assist Device Speed Optimization Studies: Insights Into Interventricular Interactions and Right Ventricular Failure.

Brener MI, Hamid NB, Fried JA, Masoumi A, ... Uriel N, Burkhoff D
Background
Interventricular interaction, which refers to the impact of left ventricular (LV) function on right ventricular (RV) function and vice versa, has been implicated in the pathogenesis of RV failure in LV assist device (LVAD) recipients. We sought to understand more about interventricular interaction by quantifying changes in the RV systolic and diastolic function with varying LVAD speeds.
Methods and results
Four patients (ages 22-69 years, 75% male, and 25% with ischemic cardiomyopathy) underwent a protocolized hemodynamic ramp test within 12 months of LVAD implantation where RV pressure-volume loops were recorded with a conductance catheter. The end-systolic PV relationship and end-diastolic PV relationship were compared using the V20 and V10 indices (volumes at which end-systolic PV relationship and end-diastolic PV relationship reach a pressure of 20 and 10 mm Hg, respectively). The ∆V20 and ∆V10 refer to the change in V20 and V10 from the minimum to maximum LVAD speeds. RV PV loops demonstrated variable changes in systolic and diastolic function with increasing LVAD speed. The end-systolic PV relationship changed in 1 patient (patient 2, ∆V20 = 23.5 mL), reflecting a decrease in systolic function with increased speed, and was unchanged in 3 patients (average ∆V20 = 7.4 mL). The end-diastolic PV relationship changed with increasing speed in 3 of 4 patients (average ∆V10 = 12.5 mL), indicating an increase in ventricular compliance, and remained unchanged in one participant (patient 1; ∆V10 = 4.0 mL).
Conclusions
Interventricular interaction can improve RV compliance and impair systolic function, but the overall effect on RV performance in this pilot investigation is heterogeneous. Further research is required to understand which patient characteristics and hemodynamic parameters influence the net impact of interventricular interaction.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 11 May 2021; epub ahead of print
Brener MI, Hamid NB, Fried JA, Masoumi A, ... Uriel N, Burkhoff D
J Card Fail: 11 May 2021; epub ahead of print | PMID: 33989781
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Impact:
Abstract

Physical Functioning in Heart Failure With Preserved Ejection Fraction.

Cosiano MF, Tobin R, Mentz RJ, Greene SJ
Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent, yet interventions and therapies to improve outcomes remain limited. There has been increasing attention towards the impact of comorbidities and physical functioning (PF) on poor clinical outcomes within this population. In this review, we summarize and discuss the literature on PF in HFpEF, its association with clinical and patient-centered outcomes, and future advances in the care of HFpEF with respect to PF. Multiple PF metrics have been demonstrated to provide prognostic value within HFpEF, yet the data are less robust compared with other patient populations, highlighting the need for further investigation. The evaluation and detection of poor PF provides a potential strategy to improve care in HFpEF, and future studies are needed to understand if modulating PF improves clinical and/or patient-reported outcomes. LAY SUMMARY: • Patients with heart failure with preserved ejection fraction (HFpEF) commonly have impaired physical functioning (PF) demonstrated by limitations across a wide range of common PF metrics.• Impaired PF metrics demonstrate prognostic value for both clinical and patient-reported outcomes in HFpEF, making them plausible therapeutic targets to improve outcomes.• Clinical trials are ongoing to investigate novel methods of detecting, monitoring, and improving impaired PF to enhance HFpEF care.Heart failure with preserved ejection fraction (HFpEF) is increasingly prevalent, yet interventions and therapies to improve outcomes remain limited. As such, there has been increasing focus on the impact of physical performance (PF) on clinical and patient-centered outcomes. In this review, we discuss the state of PF in patients with HFpEF by examining the multitude of PF metrics available, their respective strengths and limitations, and their associations with outcomes in HFpEF. We highlight future advances in the care of HFpEF with respect to PF, particularly regarding the evaluation and detection of poor PF.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 11 May 2021; epub ahead of print
Cosiano MF, Tobin R, Mentz RJ, Greene SJ
J Card Fail: 11 May 2021; epub ahead of print | PMID: 33991684
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Impact:
Abstract

Estimated Glomerular Filtration Rate Variability in Patients With Heart Failure and Chronic Kidney Disease.

Hein AM, Scialla JJ, Sun JL, Greene SJ, ... Pun PH, Mentz RJ
Background
Greater variability in the estimated glomerular filtration rate (eGFR) is associated with higher mortality in patients with chronic kidney disease (CKD). Heart failure (HF) is common in CKD and may increase variability through changes in hemodynamic and volume regulation. We sought to determine if patients with vs without HF have higher kidney function variability in CKD, and to define the association with mortality.
Methods and results
Patients undergoing coronary angiography from 2003 to 2013 with an eGFR of less than 60 mL/min/1.73 m2 were evaluated from the Duke Databank for Cardiovascular Disease. Variability in the eGFR, measured as the coefficient of variation (CV) of residuals from the regression of eGFR vs time, was calculated spanning 3 months to 2 years after catheterization. Mortality was assessed 2 to 7 years after catheterization. Patients were grouped into 3 HF phenotypes: HF with reduced ejection fraction, HF with preserved ejection, and no HF. Regression was used to evaluate associations between HF phenotypes and variability in the eGFR and between variability in the eGFR and mortality rate with stratification by HF phenotype. Among 3767 participants, the median eGFR at baseline was 45 mL/min/1.73 m2 (interquartile range 33-53 mL/min/1.73 m2), and longitudinal measures of eGFR over 21 months had within-patient residual variability (CV) of 14% (9%-20%). In adjusted analyses, variability in the eGFR was greater in those with HF with preserved ejection (n = 695, CV difference 0.98%, 95% confidence interval 0.14%-1.81%) or HF with reduced ejection fraction (n = 800, CV difference 2.51%, 95% confidence interval 1.66%-3.37%) relative to no HF (n = 2272). In 3068 participants eligible for mortality analysis, the presence of HF and greater variability in the eGFR were each associated independently with higher mortality, but there was no evidence of interaction between variability in the eGFR and any HF phenotype (all P for interaction ≥.49).
Conclusions
Variability in the eGFR is greater in patients with HF and associated with mortality. Prediction algorithms and classification schemes should consider not only static, but also dynamic eGFR variability in HF and CKD prognostication.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 09 May 2021; epub ahead of print
Hein AM, Scialla JJ, Sun JL, Greene SJ, ... Pun PH, Mentz RJ
J Card Fail: 09 May 2021; epub ahead of print | PMID: 33971291
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Abstract

Association Between β-Blockers and Outcomes in Heart Failure With Preserved Ejection Fraction: Current Insights From the SwedeHF Registry.

Meyer M, Du Fay Lavallaz J, Benson L, Savarese G, Dahlström U, Lund LH
Background
β-Blockers have an uncertain effect in heart failure with a preserved ejection fraction of 50% or higher (heart failure with preserved ejection fraction [HFpEF]).
Methods and results
We included patients with HFpEF from the Swedish Heart Failure Registry (SwedeHF) enrolled from 2011 through 2018. In a 2:1 propensity-score matched analysis (β-blocker use vs nonuse), we assessed the primary outcome first HF hospitalization, the coprimary outcome cardiovascular (CV) death, and the secondary outcomes of all-cause hospitalization and all-cause death. We performed intention-to-treat and a per-protocol consistency analyses. There were a total of 14,434 patients (median age 79 years, IQR 71-85 years, 51% women); 80% were treated with a β-blocker at baseline. Treated patients were younger and had higher rates of atrial fibrillation and coronary artery disease, and higher N-terminal pro-B-type natriuretic peptide levels. In the 4412:2206 patient matched cohort, at 5 years, 42% (95% CI 40%-44%) vs 44% (95% CI 41%-47%) had a HF admission and 38% (IQR 36%-40%) vs 40% (IQR 36%-42%) died from CV causes. In the intention-to-treat analysis, β-blocker use was not associated with HF admissions (hazard ratio 0.95 [95% CI 0.87-1.05, P = .31]) or CV death (hazard ratio 0.94 [95% CI 0.85-1.03, P = .19]). In the subgroup analyses, men seemed to have a more favorable association between β-blockers and outcomes than did women. There were no associations between β-blocker use and secondary outcomes.
Conclusions
In patients with HFpEF, β-blocker use is common but not associated with changes in HF hospitalization or cardiovascular mortality. In the absence of a strong rational and randomized control trials the case for β-blockers in HFpEF remains inconclusive.
Bullet points
● The effect of β-blockers with heart failure with preserved ejection fraction of 50% or greater is uncertain.● In a propensity score-matched heart failure with preserved ejection fraction analysis in the SwedeHF registry, β-blockers were not associated with a change in risk for heart failure admissions or cardiovascular deaths.
Lay summary
The optimal treatment for heart failure with a preserved pump function remains unknown. Despite the lack of scientific studies, β-blockers are very commonly used. When matching patients with a similar risk profile in a large heart failure registry, the use of β-blockers for the treatment of heart failure with a preserved pump function was not associated with any changes in heart failure hospital admissions or cardiovascular death.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 07 May 2021; epub ahead of print
Meyer M, Du Fay Lavallaz J, Benson L, Savarese G, Dahlström U, Lund LH
J Card Fail: 07 May 2021; epub ahead of print | PMID: 33971289
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Abstract

Salutary Acute Effects of Exercise on Central Hemodynamics in Heart Failure With Preserved Ejection Fraction.

Obokata M, Reddy YNV, Koepp KE, Stewart GM, ... Burkhoff D, Borlaug BA
Background
A warmup period of priming exercise has been shown to improve peripheral oxygen transport in older adults. We sought to determine the acute effects of priming exercise on central hemodynamics at rest and during a repeat exercise in heart failure with preserved ejection fraction (HFpEF).
Methods and results
This is a post hoc analysis from 3 studies. Patients with HFpEF (n = 42) underwent cardiac catheterization with simultaneous expired gas analysis at rest and during exercise (20 W for 5 minutes, priming exercise). Measurements were then repeated at rest and during a second bout of exercise at a 20-W workload (second exercise). During the priming exercise, patients with HFpEF displayed dramatic increases in biventricular filling pressures and exercise-induced pulmonary hypertension. After the priming exercise at rest, biventricular filling pressures and pulmonary artery (PA) pressures were lower and lung tidal volume was increased. During the second bout of exercise, biventricular filling (PA wedge pressure, 29 ± 8 mm Hg at second exercise vs 32 ± 7 mm Hg at first exercise, P = .0003) and PA pressures were lower, and PA compliance increased.
Conclusions
This study shows that short duration, submaximal priming exercise attenuates the pathologic increases in filling pressures, improving pulmonary vascular hemodynamics at rest and during repeat exercise in patients with HFpEF.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 07 May 2021; epub ahead of print
Obokata M, Reddy YNV, Koepp KE, Stewart GM, ... Burkhoff D, Borlaug BA
J Card Fail: 07 May 2021; epub ahead of print | PMID: 33974969
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Impact:
Abstract

Early Identification of Patients at Risk for Incident Heart Failure With Preserved Ejection Fraction: Novel Approach to Echocardiographic Trends.

Lekavich CL, Abraham D, Fudim M, Green C, ... Barksdale D, Kraus WE
Background
Heart failure with preserved ejection fraction (HFpEF) continues to increase in prevalence with a 50% mortality rate within 3 years of diagnosis, but lacking effective evidence-based therapies. Specific echocardiographic markers are not typically used to trigger alarm before acute HFpEF decompensation. The goal of this study was to retrospectively track changes in echocardiographic markers leading to the time of incident HFpEF hospitalization.
Methods and results
In a single-center, retrospective analysis, patients with HFpEF admitted between 2007 and 2014 were identified using the International Classification of Diseases, 9th Revision with search refined using the European Society of Cardiology HFpEF guidelines. Using linear mixed effects models, changes in echocardiographic markers preceding acute HF decompensation owing to incident HFpEF were analyzed. We report on an incident HFpEF cohort of 242 patients, extending 18 years retrospectively, and including 675 echocardiograms analyzed from the overall sample at 14 distinct time intervals before acute decompensation. The regression models demonstrated 3 echocardiographic markers with statistically significant increases across multiple time intervals including, arterial elastance (P = .006), right atrial pressure estimate (P < .001), and right ventricular systolic pressure (P = .006). Other echocardiographic markers had individual time intervals with significant increases before acute decompensation, including (a) left atrial diameter, 8 to 10 years before HFpEF diagnosis, (b) left ventricular filling pressure 2 to 6 years before HFpEF diagnosis, (c) ventricular elastance 3 to 6 months before HFpEF diagnosis, and (d) ventricular elastance/arterial elastance as early as 10 to 20 years and as late as 3 to 6 months before HFpEF diagnosis. Furthermore, African Americans presented with incident HFpEF at an average younger age than White patients (65.6 ± 15.2 years vs. 76.7 years ± 11.7, P < .001).
Conclusions
Noninvasive echocardiographic markers associated with incident HFpEF diagnosis showed long, mid, and acute range, significant changes as far back as 10 to 20 years and as close as 3 to 6 months before acute HFpEF decompensation. Including a diverse study cohort is critical to understanding the phenotypic differences of HFpEF. This hypothesis-generating study identified a novel approach to identifying trends in echocardiographic markers that may be used as a signal of impending incident HFpEF.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 06 May 2021; epub ahead of print
Lekavich CL, Abraham D, Fudim M, Green C, ... Barksdale D, Kraus WE
J Card Fail: 06 May 2021; epub ahead of print | PMID: 33965536
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Impact:
Abstract

Pulmonary Vascular Alterations on Computed Tomography Imaging and Outcomes in Heart Failure With Preserved Ejection Fraction: a Preliminary Data.

Kagami K, Takemura M, Yoshida K, Harada T, ... Kurabayashi M, Obokata M
Background
Pulmonary vascular disease may play an important role in the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). However, no study has demonstrated noninvasive quantification of pulmonary vascular alterations in HFpEF. This study sought to determine the association between pulmonary vascular alterations quantified by chest computed tomography scan and clinical outcomes in HFpEF.
Methods and results
Pulmonary vascular alterations were quantified in 151 patients with HFpEF who underwent noncontrast chest computed tomography scan by measuring the percentage of total cross-sectional area (CSA) of pulmonary vessels less than 5 mm2 to the total lung area (%CSA<5). We divided the patients by the median value of %CSA<5 (=1.45%) and examined the association between %CSA<5 and a composite outcome of all-cause mortality or HF hospitalization. During a median follow-up of 17.3 months, there were 44 (29%) composite outcomes. Event rates were significantly higher in patients with higher %CSA<5 than those with lower %CSA<5 (log-rank P = .02). %CSA<5 was associated with an increased risk of the outcome (hazard ratio per 1.0% increment, 1.46; 95% confidence interval 1.06-1.98; P = .02) in an unadjusted Cox model, and was independently and incrementally associated with the outcome over age, the presence of atrial fibrillation, E/e\' ratio, and estimated pulmonary artery systolic pressure (global χ2 17.3 vs 11.5, P = .02).
Conclusions
A higher %CSA<5 was associated with an increased risk of all-cause mortality or HF hospitalization in patients with HFpEF, with an incremental prognostic value over age, atrial fibrillation, E/e\' ratio, and pulmonary artery systolic pressure.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 06 May 2021; epub ahead of print
Kagami K, Takemura M, Yoshida K, Harada T, ... Kurabayashi M, Obokata M
J Card Fail: 06 May 2021; epub ahead of print | PMID: 33965537
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Abstract

Oral Anticoagulation and Adverse Outcomes after Ischemic Stroke in Heart Failure Patients without Atrial Fibrillation.

Saeed O, Zhang S, Patel SR, Jorde UP, ... Schwamm LH, Fonarow GC
Background
The safety and effectiveness of oral anticoagulation (OAC) after an ischemic stroke in older patients with heart failure (HF) without atrial fibrillation remains uncertain.
Methods
Utilizing Get With The Guidelines Stroke national clinical registry data linked to Medicare claims from 2009-2014, we assessed the outcomes of eligible patients with a history of HF who were initiated on OAC during a hospitalization for an acute ischemic stroke. The cumulative incidences of adverse events were calculated using Kaplan-Meier curves and adjusted Cox proportional hazard ratios were compared between patients discharged on or off OAC.
Results
A total of 8,261 patients from 1,370 sites were discharged alive after an acute ischemic stroke and met eligibility criteria. Of those, 747 (9.0%) were initiated on OAC.  Patients on OAC were younger (77.2±8.0 vs. 80.5±8.9 years, p<0.01). After adjustment for clinical covariates, the likelihood of 1 year mortality was higher in those on OAC (aHR: 1.22, 95% CI 1.05-1.41, p<0.01), while no significant differences were noted for ICH (aHR: 1.34, 95% CI 0.69-2.59, p=0.38) and recurrent ischemic stroke (aHR: 0.78, 95% CI 0.54-1.15, p = 0.21).  The likelihood of all-cause bleeding (aHR: 1.59, 95% CI 1.29-1.96, p<0.01) and all-cause re-hospitalization (aHR: 1.14, 95% CI 1.02-1.27, p = 0.02) was higher for those on OAC.
Conclusion
Initiation of OAC after an ischemic stroke in older patients with HF in the absence of atrial fibrillation is associated with death, bleeding and re-hospitalization without an associated reduction in recurrent ischemic stroke. If validated, these findings raise caution for prescribing OAC to such patients.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 03 May 2021; epub ahead of print
Saeed O, Zhang S, Patel SR, Jorde UP, ... Schwamm LH, Fonarow GC
J Card Fail: 03 May 2021; epub ahead of print | PMID: 33975786
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Abstract

Potential Utility of Cardiorenal Biomarkers for Prediction and Prognostication of Worsening Renal Function in Acute Heart Failure.

Horiuchi YU, Wettersten N, Veldhuisen DJV, Mueller C, ... Maisel A, Murray PT
Background
Multiple different pathophysiologic processes can contribute to worsening renal function (WRF) in acute heart failure.
Methods and results
We retrospectively analyzed 787 patients with acute heart failure for the relationship between changes in serum creatinine and biomarkers including brain natriuretic peptide, high sensitivity cardiac troponin I, galectin 3, serum neutrophil gelatinase-associated lipocalin, and urine neutrophil gelatinase-associated lipocalin. WRF was defined as an increase of greater than or equal to 0.3 mg/dL or 50% in creatinine within first 5 days of hospitalization. WRF was observed in 25% of patients. Changes in biomarkers and creatinine were poorly correlated (r ≤ 0.21) and no biomarker predicted WRF better than creatinine. In the multivariable Cox analysis, brain natriuretic peptide and high sensitivity cardiac troponin I, but not WRF, were significantly associated with the 1-year composite of death or heart failure hospitalization. WRF with an increasing urine neutrophil gelatinase-associated lipocalin predicted an increased risk of heart failure hospitalization.
Conclusions
Biomarkers were not able to predict WRF better than creatinine. The 1-year outcomes were associated with biomarkers of cardiac stress and injury but not with WRF, whereas a kidney injury biomarker may prognosticate WRF for heart failure hospitalization.

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

J Card Fail: 29 Apr 2021; 27:533-541
Horiuchi YU, Wettersten N, Veldhuisen DJV, Mueller C, ... Maisel A, Murray PT
J Card Fail: 29 Apr 2021; 27:533-541 | PMID: 33296713
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Abstract

Effects of Depression on Heart Failure Self-Care.

Freedland KE, Skala JA, Steinmeyer BC, Carney RM, Rich MW
Background
Depression has been identified as a barrier to effective heart failure self-care, but recent studies suggest that the relationship between depression and self-care is more complex than was previously believed. This study was designed to clarify the relationship between depression and self-care in hospitalized patients with HF.
Methods and results
During hospitalization with a confirmed clinical diagnosis of HF, 400 patients completed a structured interview to diagnose Diagnostic and Statistical Manual, 5th edition (DSM-5) depressive disorders, the Patient Health Questionnaire (PHQ-9) depression questionnaire, the Self-Care of Heart Failure Index (SCHFI), and several psychosocial questionnaires. Multivariable models were fitted to each SCHFI scale; separate models were run with DSM-5 disorders and PHQ-9 depression scores. Higher PHQ-9 depression scores were independently associated with lower (worse) scores on the SCHFI Maintenance (P < .05), Management (P < .01), and Confidence (P < .01) scales. No independent associations with DSM-5 depressive disorders were detected. Measures of perceived stress, anxiety, and low perceived social support were also significantly associated with poor HF self-care.
Conclusions
Patients with a combination of psychosocial problems, including symptoms of depression, stress, anxiety, and inadequate social support, may be more likely than other patients to display difficulties with HF self-care that can increase their risk for hospitalization. Research is needed on \"broad-spectrum\" psychosocial interventions for patients with HF self-care deficits.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 29 Apr 2021; 27:522-532
Freedland KE, Skala JA, Steinmeyer BC, Carney RM, Rich MW
J Card Fail: 29 Apr 2021; 27:522-532 | PMID: 33358958
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Abstract

Effects of Low-Level Tragus Stimulation on Endothelial Function in Heart Failure With Reduced Ejection Fraction.

Dasari TW, Csipo T, Amil F, Lipecz A, ... Yabluchanskiy A, Po SS
Background
Autonomic dysregulation in heart failure with reduced ejection fraction plays a major role in endothelial dysfunction. Low-level tragus stimulation (LLTS) is a novel, noninvasive method of autonomic modulation.
Methods and results
We enrolled 50 patients with heart failure with reduced ejection fraction (left ventricular ejection fraction of ≤40%) in a randomized, double-blinded, crossover study. On day 1, patients underwent 60 minutes of LLTS with a transcutaneous stimulator (20 Hz, 200 μs pulse width) or sham (ear lobule) stimulation. Macrovascular function was assessed using flow-mediated dilatation in the brachial artery and cutaneous microcirculation with laser speckle contrast imaging in the hand and nail bed. On day 2, patients were crossed over to the other study arm and underwent sham or LLTS; vascular tests were repeated before and after stimulation. Compared with the sham, LLTS improved flow-mediated dilatation by increasing the percent change in the brachial artery diameter (from 5.0 to 7.5, LLTS on day 1, P = .02; and from 4.9 to 7.1, LLTS on day 2, P = .003), compared with no significant change in the sham group (from 4.6 to 4.7, P = .84 on day 1; and from 5.6 to 5.9 on day 2, P = .65). Cutaneous microcirculation in the hand showed no improvement and perfusion of the nail bed showed a trend toward improvement.
Conclusions
Our study demonstrated the beneficial effects of acute neuromodulation on macrovascular function. Larger studies to validate these findings and understand mechanistic links are warranted.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 29 Apr 2021; 27:568-576
Dasari TW, Csipo T, Amil F, Lipecz A, ... Yabluchanskiy A, Po SS
J Card Fail: 29 Apr 2021; 27:568-576 | PMID: 33387632
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Abstract

Impact of Right Atrial Remodeling in Heart Failure With Preserved Ejection Fraction.

Ikoma T, Obokata M, Okada K, Harada T, ... Kurabayashi M, Murakami M
Background
Few studies have investigated right atrial (RA) remodeling in heart failure (HF) with preserved ejection fraction (HFpEF). This study sought to characterize the RA remodeling in HFpEF and to determine its prognostic significance.
Methods and results
Patients with HFpEF were classified based on the presence of RA enlargement (RA volume index >39 mL/m2 in men and >33 mL/m2 in women). Compared with patients with normal RA size (n = 234), patients with RA dilation (n = 67) showed a higher prevalence of atrial fibrillation (AF), worse right ventricular systolic function, more severe pulmonary hypertension, and a greater prevalence of mild tricuspid regurgitation, as well as impaired RA reservoir function, with increased hepatobiliary enzyme levels. AF was strongly associated with the presence of RA dilation (odds ratio [OR] 10.2, 95% confidence interval [CI] 4.00-26.1 in current AF vs no AF and odds ratio 3.38, 95% CI 1.26-9.07, earlier AF vs no AF). Patients with RA dilation had more than a two-fold increased risk of composite outcomes of all-cause mortality or HF hospitalization (adjusted hazard ratio 2.01, 95% CI 1.09-3.70, P = .02). The presence of RA dilation also displayed an additive prognostic value over left atrial dilation alone.
Conclusions
These data demonstrate that HFpEF with RA remodeling is associated with distinct echocardiographic features characterizing advanced right heart dysfunction with an increased risk of adverse outcomes.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 29 Apr 2021; 27:577-584
Ikoma T, Obokata M, Okada K, Harada T, ... Kurabayashi M, Murakami M
J Card Fail: 29 Apr 2021; 27:577-584 | PMID: 33385523
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Abstract

Understanding Longitudinal Changes in Pulmonary Vascular Resistance After Left Ventricular Assist Device Implantation.

Gulati G, Ruthazer R, Denofrio D, Vest AR, Kent D, Kiernan MS
Background
Elevated pulmonary vascular resistance (PVR) is common in patients with advanced heart failure. PVR generally improves after left ventricular assist device (LVAD) implantation, but the rate of decrease has not been quantified and the patient characteristics most strongly associated with this improvement are unknown.
Methods and results
We analyzed 1581 patients from the Interagency Registry for Mechanically Assisted Circulatory Support registry who received a primary continuous-flow LVAD, had a baseline PVR of ≥3 Wood units (WU), and had PVR measured at least once postoperatively. Multivariable linear mixed effects modeling was used to evaluate independent associations between postoperative PVR and patient characteristics. PVR decreased by 1.53 WU (95% confidence interval [CI] 1.27-1.79 WU) per month in the first 3 months postoperatively, and by 0.066 WU (95% CI 0.060-0.070 WU) per month thereafter. Severe mitral regurgitation at any time during follow-up was associated with a 1.29 WU (95% CI 1.05-1.52 WU) higher PVR relative to absence of mitral regurgitation at that time. In a cross-sectional analysis, 15%-25% of patients had persistently elevated PVR of ≥3 WU at any given time within 36 months after LVAD implantation.
Conclusion
The PVR tends to decrease rapidly early after implantation, and only more gradually thereafter. Residual mitral regurgitation may be an important contributor to elevated postoperative PVR. Future research is needed to understand the implications of elevated PVR after LVAD implantation and the optimal strategies for prevention and treatment.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Apr 2021; 27:552-559
Gulati G, Ruthazer R, Denofrio D, Vest AR, Kent D, Kiernan MS
J Card Fail: 29 Apr 2021; 27:552-559 | PMID: 33450411
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Abstract

Association between Respiratory Failure and Clinical Outcomes in Patients with Acute Heart Failure: Analysis of 5 Pooled Clinical Trials.

Miller PE, Van Diepen S, Metkus TS, Alviar CL, ... Desai NR, Ahmad T
Background
Despite a temporal increase in respiratory failure in patients hospitalized with acute heart failure (HF), clinical trials have largely not reported the incidence or associated clinical outcomes for patients requiring mechanical ventilation.
Methods and results
After pooling 5 acute HF clinical trials, we used multivariable logistic regression adjusted for demographics, comorbidities, examinations, and laboratory findings to assess associations between mechanical ventilation and clinical outcomes. Among the 8296 patients, 210 (2.5%) required mechanical ventilation. Age, sex, smoking history, baseline ejection fraction, HF etiology, and the proportion of patients randomized to treatment or placebo in the original clinical trial were similar between groups (all, P > 0.05). Baseline diabetes mellitus was more common in the mechanical ventilation group (P = 0.02), but other comorbidities, including chronic lung disease, were otherwise similar (all P > 0.05). HF rehospitalization at 30 days (12.7% vs 6.6%, P < 0.001) and all-cause 60-day mortality (33.3% vs 6.1%, P < 0.001) was higher among patients requiring mechanical ventilation. After multivariable adjustment, mechanical ventilation use was associated with an increased 30-day HF rehospitalization (odds ratio 2.03; 95% confidence interval, 1.29-3.21, P = 0.002), 30-day mortality (odds ratio 10.40; 95% confidence interval, 7.22-14.98, P < 0.001), and 60-day mortality (odds ratio 7.68; 95% confidence interval, 5.50-10.74, P < 0.001). The influence of mechanical ventilation did not differ by HF etiology or baseline ejection fraction (both, interaction P > 0.20).
Conclusions
Respiratory failure during an index hospitalization for acute HF was associated with increased rehospitalization and all-cause mortality. The development of respiratory failure during an acute HF admission identifies a particularly vulnerable population, which should be identified for closer monitoring.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Apr 2021; 27:602-606
Miller PE, Van Diepen S, Metkus TS, Alviar CL, ... Desai NR, Ahmad T
J Card Fail: 29 Apr 2021; 27:602-606 | PMID: 33556546
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Abstract

Primary Prevention Implantable Cardioverter-Defibrillator Therapy in Heart Failure with Recovered Ejection Fraction.

Baman JR, Patil KD, Medhekar AN, Wilcox JE
Given recent advances in both pharmacologic and nonpharmacologic strategies for improving outcomes related to chronic systolic heart failure, heart failure with recovered ejection fraction (HFrecEF) is now recognized as a distinct clinical entity with increasing prevalence. In many patients who once had an indication for active implantable cardioverter-defibrillator (ICD) therapy, questions remain regarding the usefulness of this primary prevention strategy to protect against syncope and cardiac arrest after they have achieved myocardial recovery. Early, small studies provide convincing evidence for continued guideline-directed medical therapy (GDMT) in segments of the HFrecEF population to promote persistent left ventricular myocardial recovery. Retrospective data suggest that the risk of sudden cardiac death is lower, but still present, in HFrecEF as compared with HF with reduced ejection fraction, with reports of up to 5 appropriate ICD therapies delivered per 100 patient-years. The usefulness of continued ICD therapy is weighed against the unfavorable effects of this strategy, which include a cumulative risk of infection, inappropriate discharge, and patient-level anxiety. Historically, many surrogate measures for risk stratification have been explored, but few have demonstrated efficacy and widespread availability. We found that the available data to inform decisions surrounding the continued use of active ICD therapies in this population are incomplete, and more advanced tools such as genetic testing, evaluation of high-risk structural cardiomyopathies (such as noncompaction), and cardiac magnetic resonance imaging have emerged as vital in risk stratification. Clinicians and patients should engage in shared decision-making to evaluate the appropriateness of active ICD therapy for any given individual. In this article, we explore the definition of HFrecEF, data underlying continuation of guideline-directed medical therapy in patients who have achieved left ventricular ejection fraction recovery, the benefits and risks of active ICD therapy, and surrogate measures that may have a role in risk stratification.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Apr 2021; 27:585-596
Baman JR, Patil KD, Medhekar AN, Wilcox JE
J Card Fail: 29 Apr 2021; 27:585-596 | PMID: 33636331
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Abstract

Impact of Socioeconomic Status on Outcomes After Ventricular Assist Device Implantation Using the Area Deprivation Index.

Han JJ, Iyengar A, Fowler C, Acker A, ... Birati EY, Atluri P
Background
This study evaluates the Area Deprivation Index (ADI) as a novel prognostic metric of socioeconomic status for patients with a left ventricular assist device.
Methods and results
A retrospective analysis of patients with a left ventricular assist device at a high-volume institution from 2007 to 2018 was conducted. Socioeconomic status was determined using the ADI, a multifactorial neighborhood-based metric where higher ADI denotes worse socioeconomic status. Patients were stratified into 4 ADI cohorts. Long-term survival was compared with multivariate analysis. Of the 380 patients stratified by ADI, 35 were in the 10th percentile or lower, 218 were in the 11th-50th percentile, 104 were in the 51st-89th percentile, and 23 were in the 90th percentile or higher. Baseline characteristics were comparable. On multivariate analysis, being male (hazard ratio [HR], 0.14; P = .01), bridge-to-transplant (HR, 0.14; P = .03), and not requiring biventricular support (HR, 0.02; P < .01) were protective, whereas chronic kidney disease (HR, 9.07; P < .01) and an elevated total bilirubin (HR, 3.56; P = .02) were harmful. The ADI as a continuous variable did not affect survival; however, categorically, a higher ADI was protective (ADI 90-100: HR, 0.07; P = .04).
Conclusions
Socioeconomically disadvantaged patients had noninferior outcomes given appropriate pre-implant optimization and workup.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Apr 2021; 27:597-601
Han JJ, Iyengar A, Fowler C, Acker A, ... Birati EY, Atluri P
J Card Fail: 29 Apr 2021; 27:597-601 | PMID: 33962744
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Abstract

Palliative Care Services in Patients Admitted With Cardiogenic Shock in the United States: Frequency and Predictors of 30-Day Readmission.

Feng Z, Fonarow GC, Ziaeian B
Background
Patients admitted with cardiogenic shock (CS) have high mortality rates, readmission rates, and healthcare costs. Palliative care services (PCS) may be underused, and the association with 30-day readmission and other predictive factors is unknown. We studied the frequency, etiologies, and predictors of 30-day readmission in CS admissions with and without PCS in the United States.
Methods and results
Using the 2017 Nationwide Readmissions Database, we identified admissions for (1) CS, (2) CS with PCS, and (3) CS without PCS. We compared differences in outcomes and predictors of readmission using multivariable logistic regression analysis accounting for survey design. Of 133,738 CS admissions nationally in 2017, 36.3% died inpatient. Among those who survived, 8.6% used PCS and 21% were readmitted within 30 days. Difference between CS with and without PCS groups included mortality (72.8% vs 27%), readmission rate (11.6% vs 21.9%), most frequent discharge destination (50.2% skilled nursing facilities vs 36.4% home), hospitalization cost per patient ($51,083 ± $2,629 vs $66,815 ± $1,729). The primary readmission diagnoses for both groups were heart failure (32.1% vs 24.4%). PCS use was associated with lower rates of readmission (odds ratio, 0.462; 95% confidence interval, 0.408-0.524; P < .001). Do-not-resuscitate status, private pay, self-pay, and cardiac arrest were negative predictors, and multiple comorbidities was a positive predictor of readmission.
Conclusions
The use of PCS in CS admissions remains low at 8.6% in 2017. PCS use was associated with lower 30-day readmission rates and hospitalization costs. PCS are associated with a decrease in future acute care service use for critically ill cardiac patients but underused for high-risk cardiac patients.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Apr 2021; 27:560-567
Feng Z, Fonarow GC, Ziaeian B
J Card Fail: 29 Apr 2021; 27:560-567 | PMID: 33962743
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Impact:
Abstract

Association of Aspirin Treatment With Cardiac Allograft Vasculopathy Progression and Adverse Outcomes After Heart Transplantation.

Asleh R, Briasoulis A, Smith B, Lopez C, ... Lerman A, Kushwaha SS
Background
Enhanced platelet reactivity may play a role in cardiac allograft vasculopathy (CAV) progression. The use of antiplatelet agents after heart transplantation (HT) has been inconsistent and although aspirin (ASA) is often a part of the medication regimen after HT, limited evidence is available on its benefit.
Methods and results
CAV progression was assessed by measuring the difference in plaque volume and plaque index between the last follow-up and the baseline coronary intravascular ultrasound examination. Overall, 529 HT recipients were retrospectively analyzed (337 had ≥2 intravascular ultrasound studies). The progression in plaque volume (P = .007) and plaque index (P = .002) was significantly attenuated among patients treated with early ASA (within the first year after HT). Over a 6.7-year follow-up, all-cause mortality was lower with early ASA compared with late or no ASA use (P < .001). No cardiac deaths were observed in the early ASA group, and the risk of CAV-related graft dysfunction was significantly lower in this group (P = .03). However, the composite of all CAV-related events (cardiac death, CAV-related graft dysfunction, or coronary angioplasty) was not significantly different between the groups (P = .16).
Conclusions
Early ASA use after HT may delay CAV progression and decrease mortality and CAV-related graft dysfunction, but does not seem to affect overall CAV-associated events.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Apr 2021; 27:542-551
Asleh R, Briasoulis A, Smith B, Lopez C, ... Lerman A, Kushwaha SS
J Card Fail: 29 Apr 2021; 27:542-551 | PMID: 33962742
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Impact:
Abstract

The Dietary Approaches to Stop Hypertension (DASH) Diet Pattern and Incident Heart Failure.

Goyal P, Balkan L, Ringel JB, Hummel SL, ... Safford MM, Levitan EB
Background
The Dietary Approaches to Stop Hypertension (DASH) diet pattern has shown some promise for preventing heart failure (HF), but studies have been conflicting.
Objective
To determine whether the DASH diet pattern was associated with incident HF in a large biracial and geographically diverse population.
Methods and results
Among participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort study of adults aged ≥45 years who were free of suspected HF at baseline in 2003-2007, the DASH diet score was derived from the baseline food frequency questionnaire. The main outcome was incident HF defined as the first adjudicated HF hospitalization or HF death through December 31, 2016. We estimated hazard ratios for the associations of DASH diet score quartiles with incident HF, and incident HF with reduced ejection fraction and HF with preserved ejection fraction using the Lunn-McNeil extension to the Cox model. We tested for several prespecified interactions, including with age. Compared with the lowest quartile, individuals in the second to fourth DASH diet score quartiles had a lower risk for incident HF after adjustment for sociodemographic and health characteristics: quartile 2 hazard ratio, 0.69 (95% confidence interval [CI], 0.56-0.85); quartile 3 hazard ratio, 0.71 (95% CI, 0.58-0.87); and quartile 4 hazard ratio, 0.73 (95% CI, 0.58-0.92). When stratifying results by age, quartiles 2-4 had a lower hazard for incident HF among those age <65 years, quartiles 3-4 had a lower hazard among those age 65-74, and the quartiles had similar hazard among those age ≥75 years (Pinteraction = .003). We did not find a difference in the association of DASH diet with incident HF with reduced ejection fraction vs HF with preserved ejection fraction (P = .11).
Conclusions
DASH diet adherence was inversely associated with incident HF, specifically among individuals <75 years old.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Apr 2021; 27:512-521
Goyal P, Balkan L, Ringel JB, Hummel SL, ... Safford MM, Levitan EB
J Card Fail: 29 Apr 2021; 27:512-521 | PMID: 33962741
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Impact:

This program is still in alpha version.