Journal: J Card Fail

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Abstract

Exception Status Listing - A Critical Pathway to Heart Transplantation For Adults with Congenital Heart Diseases.

Rali AS, Ranka S, Mazurek JA, Brinkley MD, ... Schlendorf K, Menachem JN
Adults with congenital heart diseases may not be candidates for conventional therapies for ventricular systolic dysfunction including MCS which moves potential heart transplantation recipients to a higher priority listing status. This results in longer wait list times and mortality. Exception status listing allows for one pathway for this complex and anatomically heterogenous group of patients to be listed for heart transplantation at appropriately high listing status. Our study queried the United Network for Organ Sharing (UNOS) registry to evaluate trends in utilization of exception status listing amongst adults with congenital heart diseases awaiting heart transplantation. While uptrend in utilization of exception status listing precedes the new allocation system, it been greatest since change in allocation system. It continues to remain a vital pathway in allowing adults with CHD, whose waitlist mortality is often not adequately characterized using the waitlist status criteria, timely access to heart transplantation.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 16 Oct 2021; epub ahead of print
Rali AS, Ranka S, Mazurek JA, Brinkley MD, ... Schlendorf K, Menachem JN
J Card Fail: 16 Oct 2021; epub ahead of print | PMID: 34670174
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Abstract

Associations between prognostic awareness, acceptance of illness and psychological and spiritual well-being among patients with heart failure.

Ozdemir S, Lee JJ, Malhotra C, Teo I, ... Sim KLD, Finkelstein E
Background
This study aimed to (1) investigate the association of prognostic awareness with psychological (distress and emotional well-being) and spiritual well-being among patients with heart failure, and (2) assess the main and moderating effects of illness acceptance on the relationship between prognostic awareness and psychological (distress level and emotional well-being) and spiritual well-being.
Methods and results
This study used baseline data of a Singapore cohort of patients with heart failure (n=245) who had New York Heart Association class 3 or 4 symptoms. Patients reported their awareness of prognosis and extent of illness acceptance. Multivariable linear regressions were used to investigate the associations. Prognostic awareness was not significantly associated with psychological and spiritual well-being. Illness acceptance was associated with lower levels of distress [β (SE) = -0.9 (0.2); p<0.001], higher emotional well-being [β (SE) = 2.2 (0.4); p<0.001], and higher spiritual well-being [β (SE) = 5.4 (0.7); p<0.001]. Illness acceptance did not moderate the associations of prognostic awareness with psychological and spiritual well-being.
Conclusions
This study suggests that illness acceptance could be a key factor in improving patient well-being. Illness acceptance should be regularly assessed and interventions to enhance illness acceptance should be considered for those with poor acceptance.

Copyright © 2021 Elsevier Ltd. All rights reserved.

J Card Fail: 12 Oct 2021; epub ahead of print
Ozdemir S, Lee JJ, Malhotra C, Teo I, ... Sim KLD, Finkelstein E
J Card Fail: 12 Oct 2021; epub ahead of print | PMID: 34655774
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Abstract

Diabetes Mellitus in Advanced Heart Failure.

Dunlay SM, Killian JM, McCoy RG, Redfield MM
Background
Diabetes mellitus is associated with increased mortality in patients with less severe (stage C) HF. The prevalence of diabetes and its complications in advanced (stage D) HF and their contributions to mortality risk, are unknown.
Methods and results
We conducted a retrospective population-based cohort study of all adult residents of Olmsted County, Minnesota with advanced HF between 2007-2017. Patients with diabetes were identified using HEDIS criteria. Diabetes complications were captured using the Diabetes Complications Severity Index (DCSI). Of 936 patients with advanced HF, 338 (36.1%) had diabetes. Overall, median (IQR) survival after development of advanced HF was 13.1 (3.9-33.1) months; mortality did not vary by diabetes status (aHR 1.06, 95% CI 0.90-1.25, p=0.45) or by HbA1c in those with diabetes (aHR 1.01 per 1% increase, 95% CI 0.93-1.10, p=0.82). However, patients with diabetes and 4 (aHR 1.24, 95% CI 0.92-1.67) or 5-7 (aHR 1.49, 95% CI 1.09-2.03) diabetes complications were at increased mortality risk compared to those with ≤3 complications.
Conclusions
More than one-third of patients with advanced HF have diabetes. In advanced HF, overall prognosis is poor, but we found no evidence that diabetes is associated with a significantly higher mortality risk.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 10 Oct 2021; epub ahead of print
Dunlay SM, Killian JM, McCoy RG, Redfield MM
J Card Fail: 10 Oct 2021; epub ahead of print | PMID: 34648970
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Abstract

Full Time Cardiac Intensive Care Unit Staffing by Heart Failure Specialists and Association with Mortality.

Sims DB, Kim Y, Kalininskiy A, Yanamandala M, ... Shah A, Jorde UP
Background
Cardiac intensive care units (CICUs) serve medically complex patients with multi-organ dysfunction. Whether a CICU staffed full time by heart failure (HF) specialists is associated with decreased mortality is unclear.
Methods and results
Retrospective review of consecutive CICU admissions from January 1, 2012 to Dec 31, 2016 was performed. In January 2014, the CICU changed from an open unit staffed by any cardiologist to a closed unit managed by HF specialists. Patients\' baseline characteristics were determined, and a multivariate regression analysis was performed to ascertain CICU mortality. Baseline severity of illness was higher in the closed/HF specialist CICU model (p<0.001). Death occurred in 101 of 1,185 CICU admissions (8.5%) in the open unit model and in 139 of 2,163 admissions (6.4%) in the closed/HF specialist model (absolute risk reduction 2.1%, 95% confidence interval [CI] 0.1-4.0%, p =0.01). The transition from an open to a closed/HF specialist model was associated with a lower overall CICU mortality (odds ratio [OR] 0.63; 95% CI 0.43-0.93). Prespecified interaction of a mechanical circulatory support (MCS) device and unit model showed that treatment with MCS was associated with lower CICU mortality in the closed/HF specialist model (OR 0.6; 95% CI 0.18-0.78, p for interaction <0.01).
Conclusion
Transition to a closed unit model staffed with a dedicated HF specialist is associated with lower CICU mortality.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 07 Oct 2021; epub ahead of print
Sims DB, Kim Y, Kalininskiy A, Yanamandala M, ... Shah A, Jorde UP
J Card Fail: 07 Oct 2021; epub ahead of print | PMID: 34634449
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Abstract

Hospitalization for heart failure in the USA, UK, Taiwan and Japan: an international comparison of administrative health records on 417,385 individual patients.

Sundaram V, Nagai T, Chiang CE, Reddy YN, ... Sahadevan J, Quint JK
Background
Registries show international variations in the characteristics and outcome of patients with heart failure (HF) but national samples are rarely large, and case-selection may be biased due to enrolment in academic centres. National administrative datasets provide large samples with a low risk of bias. In this study, we compared the characteristics, healthcare resource utilization (HRU) and outcomes of patients with primary HF hospitalizations (HFH) using electronic health records (EHR) from four high-income countries (USA, UK, Taiwan, Japan) on three continents.
Methods and results
We used EHR to identify unplanned HFH between 2012-2014. We identified 231,512, 10,991, 36,900 and 133,982 patients with a primary HFH from USA, UK, Taiwan and Japan, respectively. HFH per 100,000 population was highest in USA and lowest in Taiwan. Patients in Taiwan and Japan were older but fewer were obese or had chronic kidney disease. LOHS was shortest in USA (median 4 days) and longer in UK, Taiwan and Japan (medians 7, 9 and 17 days, respectively). HRU during hospitalization was highest in Japan and lowest in UK. Crude and direct standardized in-hospital mortality was lowest in USA (direct standardized rates: 1.8 [95%CI:1.7-1.9]%)and progressively higher in Taiwan (direct standardized rates: 3.9 [95%CI:3.8-4.1]%), UK (direct standardized rates: 6.4 [95%CI:6.1-6.7]%) and Japan (direct standardized rates: 6.7 [95%CI:6.6-6.8]%). 30-day all-cause (25.8%) and HF (7.2%) readmissions were highest in USA and lowest in Japan (11.9% and 5.1% respectively).
Conclusion
Marked international variations in patient characteristics, HRU and clinical outcome exist; understanding them might inform health care policy and international trial design.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 07 Oct 2021; epub ahead of print
Sundaram V, Nagai T, Chiang CE, Reddy YN, ... Sahadevan J, Quint JK
J Card Fail: 07 Oct 2021; epub ahead of print | PMID: 34634448
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Abstract

Clinical Implications of the Amyloidogenic V122I Transthyretin Variant in the General Population.

Kozlitina J, Garg S, Drazner MH, Matulevicius SA, ... de Lemos JA, Grodin JL
Aims
The V122I variant in transthyretin (TTR) is the most common amyloidogenic mutation worldwide. The aim of this study is to describe the cardiac phenotype and risk for adverse cardiovascular outcomes of young V122I TTR carriers in the general population.
Methods and results
TTR genotypes were extracted from whole-exome sequence data in participants of the Dallas Heart Study. Participants with African ancestry, available V122I TTR genotypes (N=1,818), and either cardiac magnetic resonance imaging (CMR) (n=1,364), or long-term follow-up (n=1,532) were included. The prevalence of V122I TTR carriers (45±10 years) was 3.2% (n/N=59/1,818). V122I TTR carriers had higher baseline LV wall thickness (LVWT, 8.52±1.82 vs. 8.21±1.62 mm; adjusted P=0.038) than non-carriers, but no differences in other CMR measures (P>0.05 for all). Although carrier status was not associated with amino terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline (P=0.79), V122I TTR carriers had a greater increase in NT-proBNP on follow-up than non-carriers (median [interquartile range] 28.5 [11.4-104.1] vs. 15.9 [0.0-43.0] pg/mL; adjusted P=0.018). V122I TTR carriers were at a higher adjusted risk of heart failure (HF) (HR 3.82, 95% CI 1.80-8.13, P<0.001), cardiovascular death (HR 2.65, 95% CI 1.14-6.15, P=0.023), and all-cause mortality (HR 1.95, 95% CI 1.08-3.51, P=0.026) in comparison with non-carriers.
Conclusion
V122I TTR carrier status was associated with a greater increase in NT-proBNP, slightly greater LVWT, and a higher risk for HF, cardiovascular death, and all-cause mortality. These findings suggest the need to develop amyloidosis screening strategies for V122I TTR carriers.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 07 Oct 2021; epub ahead of print
Kozlitina J, Garg S, Drazner MH, Matulevicius SA, ... de Lemos JA, Grodin JL
J Card Fail: 07 Oct 2021; epub ahead of print | PMID: 34634447
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Abstract

Multiple Cardiac Biomarker Testing Among Patients with Acute Dyspnea from the ICON-RELOADED Study.

Abboud A, Kui N, Gaggin HK, Ibrahim NE, ... Walters EL, Januzzi JL
Background
Among patients with acute dyspnea, concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT) and insulin-like growth factor binding protein-7 (IGFBP7) predict cardiovascular outcomes and death. Understanding the optimal means to interpret these elevated biomarkers in patients presenting with acute dyspnea remains unknown.
Methods and results
Concentrations of NT-proBNP, hs-cTnT, and IGFBP7 were analyzed in 1,448 patients presenting with acute dyspnea from the prospective, multicenter ICON-RELOADED (International Collaborative of NT-proBNP-Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department) Study. Eight biogroups were derived based upon patterns in biomarker elevation at presentation and compared for differences in baseline characteristics. Of 441 patients with elevations in all three biomarkers, 218 (49.4%) were diagnosed with acute heart failure (HF). The frequency of acute HF diagnosis in this biogroup was higher than those with elevations in two biomarkers (18.8%, 44 out of 234), one biomarker (3.8%, 10 out of 260), or no elevated biomarkers (0.4%, 2 out of 513). The absolute number of elevated biomarkers on admission was prognostic of the composite endpoint of mortality and HF rehospitalization. In adjusted models, patients with one, two, and three elevated biomarkers had 3.74 (95% CI, 1.26-11.1; P=0.017), 12.3 (95% CI, 4.60-32.9; P <0.001), and 12.6 (95% CI, 4.54-35.0; P <0.001) fold increased risk of 180-day mortality or HF rehospitalization.
Conclusions
A multimarker panel of NT-proBNP, hsTnT, and IGBFP7 provides unique clinical, diagnostic and prognostic information in patients presenting with acute dyspnea. Differences in the number of elevated biomarkers at presentation may allow for more efficient clinical risk stratification of short-term mortality and HF rehospitalization.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 07 Oct 2021; epub ahead of print
Abboud A, Kui N, Gaggin HK, Ibrahim NE, ... Walters EL, Januzzi JL
J Card Fail: 07 Oct 2021; epub ahead of print | PMID: 34634446
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Abstract

Divergent Trends in Emergency Department Presentations Amidst the Novel Coronavirus Disease 2019 Pandemic in Chicago, Illinois.

Khan SS, Furmanchuk A, Seegmiller LE, Ahmad FS, Black BS, O\'Leary KJ
Excess deaths during the COVID-19 pandemic have been largely attributed to cardiovascular disease (CVD); however, patterns in CVD hospitalizations following the first surge of the pandemic have not well-documented. Our brief report, examining trends in healthcare avoidance documents that CVD hospitalizations declined in Chicago prior to significant burden of COVID-19 cases or deaths and normalized during the first COVID-19 surge. These data may help inform healthcare systems responses in the coming months while mobilizing vaccinations to the population at-large.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 06 Oct 2021; epub ahead of print
Khan SS, Furmanchuk A, Seegmiller LE, Ahmad FS, Black BS, O'Leary KJ
J Card Fail: 06 Oct 2021; epub ahead of print | PMID: 34628016
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Abstract

Trends in ICD Implantations and In-Hospital Outcomes after DOJ Investigation.

Bourdillon PM, Parzynski CS, Minges KE, Curtis JP, Desai NR
Background
The Department of Justice (DOJ) investigated implantable cardioverter-defibrillators (ICDs) not meeting the Centers for Medicare & Medicaid Services National Coverage Determination (NCD) criteria, resulting in increased adherence to the NCD. Trends of the specific reasons for patients not meeting the NCD and in-hospital outcomes for those patients are not known.
Methods
We analyzed 300,151 primary prevention ICDs from 2007-2015 at 1809 hospitals. We calculated rates of in-hospital adverse events and the proportion of ICDs not meeting four NCD criteria before and after the announcement of the DOJ investigation, stratified by whether hospitals paid settlements to the DOJ.
Results
Most reductions in devices not meeting NCD were among patients with recently diagnosed heart failure (15.5% to 6.8% for settled; 13.5% to 7.3% for non-settled) and with a recent myocardial infarction (8.4% to 1.3% for settled; 7.4% to 1.5% for non-settled). Adverse event rates were significantly higher for ICDs not meeting NCD criteria (odds ratio 1.26 for settled, p < 0.001; 1.18 for non-settled, p = 0.001).
Conclusions
Following the investigation, there was a rapid reduction in ICDs placed for patients with a recent AMI or recent HF diagnosis. Patients who don\'t meet NCD criteria experienced more in-hospital adverse events and mortality.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 06 Oct 2021; epub ahead of print
Bourdillon PM, Parzynski CS, Minges KE, Curtis JP, Desai NR
J Card Fail: 06 Oct 2021; epub ahead of print | PMID: 34628015
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Abstract

The association between socioeconomic status, sex, race/ethnicity and in-hospital mortality among patients hospitalized for heart failure.

Averbuch T, Mohamed MO, Islam S, DeFilippis EM, ... Mamas MA, Van Spall H
Background
The association between socioeconomic status (SES), sex, race/ethnicity and outcomes during hospitalization for heart failure (HF) has not previously been investigated.
Methods
We analyzed HF hospitalizations in the United States National Inpatient Sample between 2015-2017. Using a hierarchical, multivariable Poisson regression model to adjust for hospital- and patient-level factors, we assessed the association between SES, sex, and race/ethnicity and all-cause in-hospital mortality. We estimated the direct costs (USD) across SES groups.
Results
Among 4,287,478 HF hospitalizations, 40.8% were in high SES, 48.7% in female, and 70.0% in White patients. Relative to these comparators, low SES (homelessness or lowest quartile of median neighborhood income) (Relative risk [RR] 1.02, 95% CI 1.00-1.05) and male sex (RR 1.09, 95% CI 1.07-1.11) were associated with increased risk, whilst Black (RR 0.79, 95% CI 0.76-0.81) and Hispanic (RR 0.90, 95% CI 0.86-0.93) race/ethnicity were associated with reduced risk of in-hospital death. There were significant interactions between race/ethnicity and both, SES (p<0.01) and sex (p=0.04) such that racial/ethnic differences in outcome were more pronounced in low SES groups and in male patients. The median direct cost of admission was lower in low vs high SES groups ($9324.60 vs $10940.40), female patients vs male patients ($9866.60 vs $10217.10), and Black vs White patients ($9077.20 vs $10019.80). The median costs increased with SES in all demographic groups.
Conclusions
SES, race/ethnicity, and sex were independently associated with in-hospital mortality during HF hospitalization, highlighting possible care disparities. Racial/ethnic differences in outcome were more pronounced in low SES groups and in male patients.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 06 Oct 2021; epub ahead of print
Averbuch T, Mohamed MO, Islam S, DeFilippis EM, ... Mamas MA, Van Spall H
J Card Fail: 06 Oct 2021; epub ahead of print | PMID: 34628014
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Abstract

Polypharmacy in Palliative Care for Advanced Heart Failure: The PAL-HF Experience.

Granger BB, Tulsky JA, Kaufman BG, Clare RM, ... Rogers JG, Mentz RJ
Background
Palliative care (PC) in advanced heart failure (HF) aims to improve symptoms and quality of life (QOL), in part through medication management. The impact of PC on polypharmacy (>5 medications) remains unknown.
Methods and results
We explored patterns of polypharmacy in the Palliative Care in HF (PAL-HF) randomized controlled trial of standard care versus interdisciplinary PC in advanced HF (N=150). We describe differences in medication counts between arms at 2, 6, 12, and 24 weeks for HF (12 classes) and PC (6 classes) medications. General linear mixed models were used to evaluate associations between treatment arm and polypharmacy over time. The median age of the patients was 72 (62-80) years, and 47% were female while 41% were Black. Overall, 48% had ischemic etiology, and 55% had an ejection fraction </= 40%. Polypharmacy was present at baseline in 100% of patients. HF and PC medication counts increased in both arms, with no significant differences in counts by drug class at any time-point between arms.
Conclusion
In a trial of patients with advanced HF considered eligible for PC, polypharmacy was universal at baseline and increased during follow-up with no effect of the palliative intervention on medication counts relative to standard care.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 06 Oct 2021; epub ahead of print
Granger BB, Tulsky JA, Kaufman BG, Clare RM, ... Rogers JG, Mentz RJ
J Card Fail: 06 Oct 2021; epub ahead of print | PMID: 34628013
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Abstract

Estimation of Stressed Blood Volume in Patients With Cardiogenic Shock From Acute Myocardial Infarction and Decompensated Heart Failure.

Whitehead EH, Thayer KL, Sunagawa K, Hernandez-Montfort J, ... Kapur NK, Burkhoff D
Background
Sympathetically mediated redistribution of blood from the unstressed venous reservoir to the hemodynamically active stressed compartment is thought to contribute to congestion in cardiogenic shock (CS). We used a novel computational method to estimate stressed blood volume (SBV) in CS and assess its relationship with clinical outcomes.
Methods and results
Hemodynamic parameters including estimated SBV (eSBV) were compared among patients from the Cardiogenic Shock Working Group registry with a complete set of hemodynamic data. eSBV was compared across shock etiologies (acute myocardial infarction and CS (AMI-CS) vs heart failure with CS (HF-CS), Society for Cardiovascular Angiography and Interventions stage, and between survivors and nonsurvivors. Among 528 patients with patients analyzed, the mean eSBV was 2423 mL/70 kg and increased with increasing Society for Cardiovascular Angiography and Interventions stage (B, 2029 mL/70 kg; C, 2305 mL/70 kg; D, 2496 mL/70 kg; E, 2707 mL/70 kg; P < .001). The eSBV was significantly greater among patients with HF-CS who died compared with survivors (2733 vs 2357 mL/70 kg; P < .001), whereas no significant difference was observed between outcome groups in AMI-CS (2501 mL/70 kg vs 2384 mL/70 kg; P = .19).
Conclusions
eSBV is a novel integrated index of congestion which correlates with shock severity. eSBV was higher in patients with HF-CS who died; no difference was observed in patients with AMI-CS, suggesting that congestion may play a more significant role in the deterioration of patients with HF-CS.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Sep 2021; 27:1141-1145
Whitehead EH, Thayer KL, Sunagawa K, Hernandez-Montfort J, ... Kapur NK, Burkhoff D
J Card Fail: 29 Sep 2021; 27:1141-1145 | PMID: 33862252
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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: 29 Sep 2021; 27:1045-1052
Belkin MN, Kalantari S, Kanelidis AJ, Miller T, ... Kim G, Grinstein J
J Card Fail: 29 Sep 2021; 27:1045-1052 | PMID: 34048919
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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: 29 Sep 2021; 27:1053-1060
Amar M, Lam SW, Faulkenberg K, Perez A, Tang WHW, Williams JB
J Card Fail: 29 Sep 2021; 27:1053-1060 | PMID: 34051349
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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 3383 consecutive patients discharged for acute HF. Of them, in 1435 patients (42.4%), the pulmonary artery systolic pressure could not be measured accurately, leaving a final sample size of 1948 patients. Advanced RHD was defined as the combination of a ratio of tricuspid annular plane systolic excursion/pulmonary artery systolic pressure of less than 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 (interquartile range 0.63-4.71), 3782 readmissions were registered in 1296 patients (66.5%). Patients with advanced RHD showed higher readmission rates, but only if the LVEF was 40% or greater (P < .001). In multivariable analyses, this differential association persisted for cardiovascular and HF recurrent admissions (P value for interaction = .015 and P = .016; respectively). Advanced RHD was independently associated with the risk of recurrent cardiovascular and HF admissions if HF with an LVEF of 40% or greater (incidence rate ratio 1.64, 95% confidence interval 1.18-2.26, P = .003; and incidence rate ratio 1.73; 95% confidence interval 1.25-2.41, P = .001;respectively). In contrast, it was not associated with readmission risks if the LVEF was less than 40%.
Conclusions
After an admission for acute HF, advanced RHD was strongly associated with a higher risk of recurrent cardiovascular and HF admissions, but only in patients with an LVEF of 40% or greater.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Sep 2021; 27:1090-1098
Santas E, Miñana G, Palau P, Espriella R, ... Bayes-Genís A, Núñez J
J Card Fail: 29 Sep 2021; 27:1090-1098 | PMID: 34273477
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Abstract

Heart Failure-Related Cardiogenic Shock: Pathophysiology, Evaluation and Management Considerations: Review of Heart Failure-Related Cardiogenic Shock.

Abraham J, Blumer V, Burkhoff D, Pahuja M, ... Hernandez-Montfort JA, Kapur NK
Despite increasing prevalence in critical care units, cardiogenic shock related to HF (HF-CS) is incompletely understood and distinct from acute myocardial infarction related CS. This review highlights the pathophysiology, evaluation, and contemporary management of HF-CS.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Sep 2021; 27:1126-1140
Abraham J, Blumer V, Burkhoff D, Pahuja M, ... Hernandez-Montfort JA, Kapur NK
J Card Fail: 29 Sep 2021; 27:1126-1140 | PMID: 34625131
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Abstract

Quality of Heart Failure Care in the Intensive Care Unit.

Metkus TS, Lindsley J, Fair L, Riley S, ... Hsu S, Gilotra NA
Patients with heart failure (HF) who are seen in an intensive care unit (ICU) manifest the highest-risk, most complex and most resource-intensive disease states. These patients account for a large relative proportion of days spent in an ICU. The paradigms by which critical care is provided to patients with HF are being reconsidered, including consideration of various multidisciplinary ICU staffing models and the development of acute-response teams. Traditional HF quality initiatives have centered on the peri- and postdischarge period in attempts to improve adherence to guideline-directed therapies and reduce readmissions. There is a compelling rationale for expanding high-quality efforts in treating patients with HF who are receiving critical care so we can improve outcomes, reduce preventable harm, improve teamwork and resource use, and achieve high health-system performance. Our goal is to answer the following question: For a patient with HF in the ICU, what is required for the provision of high-quality care? Herein, we first review the epidemiology of HF syndromes in the ICU and identify relevant critical care and quality stakeholders in HF. We next discuss the tenets of high-quality care for patients with HF in the ICU that will optimize critical care outcomes, such as ICU staffing models and evidence-based management of cardiac and noncardiac disease. We discuss strategies to mitigate preventable harm, improve ICU culture and conduct outcomes review, and we conclude with our summative vision of high-quality of ICU care for patients with HF; our vision includes clinical excellence, teamwork and ICU culture.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Sep 2021; 27:1111-1125
Metkus TS, Lindsley J, Fair L, Riley S, ... Hsu S, Gilotra NA
J Card Fail: 29 Sep 2021; 27:1111-1125 | PMID: 34625130
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Abstract

Risk Prediction in Cardiogenic Shock: Current State of Knowledge, Challenges and Opportunities.

Kalra S, Ranard LS, Memon S, Rao P, ... Fried JA, Burkhoff D
Cardiogenic shock (CS) is a condition associated with high mortality rates in which prognostication is uncertain for a variety of reasons, including its myriad causes, its rapidly evolving clinical course and the plethora of established and emerging therapies for the condition. A number of validated risk scores are available for CS prognostication; however, many of these are tedious to use, are designed for application in a variety of populations and fail to incorporate contemporary hemodynamic parameters and contemporary mechanical circulatory support interventions that can affect outcomes. It is important to separate patients with CS who may recover with conservative pharmacological therapies from those in who may require advanced therapies to survive; it is equally important to identify quickly those who will succumb despite any therapy. An ideal risk-prediction model would balance incorporation of key hemodynamic parameters while still allowing dynamic use in multiple scenarios, from aiding with early decision making to device weaning. Herein, we discuss currently available CS risk scores, perform a detailed analysis of the variables in each of these scores that are most predictive of CS outcomes and explore a framework for the development of novel risk scores that consider emerging therapies and paradigms for this challenging clinical entity.

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

J Card Fail: 29 Sep 2021; 27:1099-1110
Kalra S, Ranard LS, Memon S, Rao P, ... Fried JA, Burkhoff D
J Card Fail: 29 Sep 2021; 27:1099-1110 | PMID: 34625129
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Abstract

Lactate Clearance Is Associated With Improved Survival in Cardiogenic Shock: A Systematic Review and Meta-Analysis of Prognostic Factor Studies.

Marbach JA, Stone S, Schwartz B, Pahuja M, ... Rabinowitz JB, Kapur NK
Objective
Elevated blood lactate levels are strongly associated with mortality in patients with cardiogenic shock. Recent evidence suggests that the degree and rate at which blood lactate levels decrease after the initiation of treatment may be equally important in patient prognosis. We performed a systematic review and meta-analysis to evaluate the usefulness of lactate clearance as a prognostic factor in cardiogenic shock.
Methods and results
We performed searches of Ovid MEDLINE, Elsevier EMBASE, EBM Reviews-Cochrane Central Register of Controlled Trials, and Web of Science to identify studies comparing lactate clearance between survivors and nonsurvivors at one or more timepoints. Both prospective and retrospective studies were eligible for inclusion. Two study investigators independently screened, extracted data, and assessed the quality of all included studies. Twelve studies were included in the meta-analysis. The median lactate clearance at 6-8 hours was 21.9% (interquartile range [IQR] 14.6%-42.1%) in survivors and 0.6% (IQR -3.7% to 14.6%) in nonsurvivors. At 24 hours, the median lactate clearance was 60.7% (IQR 58.1%-76.3%) and 40.3% (IQR 30.2%-55.8%) in survivors and nonsurvivors, respectively. Accordingly, the pooled mean difference in lactate clearance between survivors and nonsurvivors at 6-8 hours was 17.3% (95% CI 11.6%-23.1%, P < .001) at 6-8 hours and 27.9% (95% CI 14.1%-41.7%, P < .001) at 24 hours.
Conclusions
Survivors had significantly greater lactate clearance at 6-8 hours and at 24 hours compared with nonsurvivors, suggesting that lactate clearance is an important prognostic marker in cardiogenic shock.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Sep 2021; 27:1082-1089
Marbach JA, Stone S, Schwartz B, Pahuja M, ... Rabinowitz JB, Kapur NK
J Card Fail: 29 Sep 2021; 27:1082-1089 | PMID: 34625128
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Abstract

De Novo vs Acute-on-Chronic Presentations of Heart Failure-Related Cardiogenic Shock: Insights from the Critical Care Cardiology Trials Network Registry.

Bhatt AS, Berg DD, Bohula EA, Alviar CL, ... Van Diepen S, Morrow DA
Background
Heart failure-related cardiogenic shock (HF-CS) accounts for an increasing proportion of cases of CS in contemporary cardiac intensive care units. Whether the chronicity of HF identifies distinct clinical profiles of HF-CS is unknown.
Methods and results
We evaluated admissions to cardiac intensive care units for HF-CS in 28 centers using data from the Critical Care Cardiology Trials Network registry (2017-2020). HF-CS was defined as CS due to ventricular failure in the absence of acute myocardial infarction and was classified as de novo vs acute-on-chronic based on the absence or presence of a prior diagnosis of HF, respectively. Clinical features, resource use, and outcomes were compared among groups. Of 1405 admissions with HF-CS, 370 had de novo HF-CS (26.3%), and 1035 had acute-on-chronic HF-CS (73.7%). Patients with de novo HF-CS had a lower prevalence of hypertension, diabetes, coronary artery disease, atrial fibrillation, and chronic kidney disease (all P < 0.01). Median Sequential Organ Failure Assessment (SOFA) scores were higher in those with de novo HF-CS (8; 25th-75th: 5-11) vs acute-on-chronic HF-CS (6; 25th-75th: 4-9, P < 0.01), as was the proportion of Society of Cardiovascular Angiography and Intervention (SCAI) shock stage E (46.1% vs 26.1%, P < 0.01). After adjustment for clinical covariates and preceding cardiac arrest, the risk of in-hospital mortality was higher in patients with de novo HF-CS than in those with acute-on-chronic HF-CS (adjusted hazard ratio 1.36, 95% confidence interval 1.05-1.75, P = 0.02).
Conclusions
Despite having fewer comorbidities, patients with de novo HF-CS had more severe shock presentations and worse in-hospital outcomes. Whether HF disease chronicity is associated with time-dependent compensatory adaptations, unique pathobiological features and responses to treatment in patients presenting with HF-CS warrants further investigation.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 29 Sep 2021; 27:1073-1081
Bhatt AS, Berg DD, Bohula EA, Alviar CL, ... Van Diepen S, Morrow DA
J Card Fail: 29 Sep 2021; 27:1073-1081 | PMID: 34625127
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Abstract

Right Ventricular Dysfunction Is Common and Identifies Patients at Risk of Dying in Cardiogenic Shock.

Jain P, Thayer KL, Abraham J, Everett KD, ... Burkhoff D, Kapur NK
Background
Understanding the prognostic impact of right ventricular dysfunction (RVD) in cardiogenic shock (CS) is a key step toward rational diagnostic and treatment algorithms and improved outcomes. Using a large multicenter registry, we assessed (1) the association between hemodynamic markers of RVD and in-hospital mortality, (2) the predictive value of invasive hemodynamic assessment incorporating RV evaluation, and (3) the impact of RVD severity on survival in CS.
Methods and results
Inpatients with CS owing to acute myocardial infarction (AMI) or heart failure (HF) between 2016 and 2019 were included. RV parameters (right atrial pressure, right atrial/pulmonary capillary wedge pressure [RA/PCWP], pulmonary artery pulsatility index [PAPI], and right ventricular stroke work index [RVSWI]) were assessed between survivors and nonsurvivors, and between etiology and SCAI stage subcohorts. Multivariable logistic regression analysis determined hemodynamic predictors of in-hospital mortality; the resulting models were compared with SCAI staging alone. Nonsurvivors had a significantly higher right atrial pressure and RA/PCWP and lower PAPI and RVSWI than survivors, consistent with more severe RVD. Compared with AMI, patients with HF had a significantly lower RA/PCWP (0.58 vs 0.66, P = .001) and a higher PAPI (2.71 vs 1.78, P < .001) and RVSWI (5.70 g-m/m2 vs 4.66 g-m/m2, P < .001), reflecting relatively preserved RV function. Paradoxically, multiple RVD parameters (PAPI, RVSWI) were associated with mortality in the HF but not the AMI cohort. RVD was more severe with advanced SCAI stage, although its prognostic value was progressively diluted in stages D and E. Multivariable modelling incorporating the RA/PCWP improved the predictive value of SCAI staging (area under the curve [AUC] 0.78 vs 0.73, P < .001), largely driven by patients with HF (AUC 0.82 vs 0.71, P < .001).
Conclusions
RVD is associated with poor outcomes in CS, with key differences across etiology and shock severity. Further studies are needed to assess the usefulness of RVD assessment in guiding therapy.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 29 Sep 2021; 27:1061-1072
Jain P, Thayer KL, Abraham J, Everett KD, ... Burkhoff D, Kapur NK
J Card Fail: 29 Sep 2021; 27:1061-1072 | PMID: 34625126
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Abstract

Non-Invasive Venous waveform Analysis (NIVA) correlates with pulmonary capillary wedge pressure (PCWP) and predicts 30-day admission in heart failure patients undergoing right heart catheterization: NIVA Scores correlate with PCWP and predicts 30-day admission.

Alvis B, Huston J, Schmeckpeper J, Polcz M, ... Hocking KM, Lindenfeld J
Background
Heart failure is the leading cause of hospitalization in the elderly and readmission is common. Clinical indicators of congestion may not precede acute congestion with enough time to prevent hospital admission for heart failure. Thus, there is a large and unmet need for accurate non-invasive assessment of congestion. Non-Invasive Venous waveform Analysis in heart failure (NIVAHF) is a novel, non-invasive technology that monitors intravascular volume status and hemodynamic congestion. The objective of this study was to determine the correlation of NIVAHF with pulmonary capillary wedge pressure (PCWP) and the ability of NIVAHF to predict 30-day admission after right heart catheterization (RHC).
Methods
The prototype NIVAHF device was compared to PCWP in 106 subjects undergoing RHC. The NIVAHF algorithm was developed and trained to estimate PCWP. NIVA Scores and central hemodynamic parameters [(PCWP, pulmonary artery diastolic pressure (PAD), and cardiac output (CO)] were evaluated in 84 patients undergoing outpatient RHC. Receiver Operating Characteristic (ROC) curves were used to determine whether a NIVA Score predicted 30-day hospital admission.
Results
The NIVA Score demonstrated a positive correlation with PCWP (r=0.92, n=106, p<0.0001). NIVA Score at time of hospital discharge predicted 30-day admission with an AUC of 0.84, a NIVA Score >18 predicted admission with a sensitivity of 91% and specificity of 56%. Residual analysis suggested that no single patient demographic confounded the predictive accuracy of the NIVA Score.
Conclusions
NIVAHF is a non-invasive monitoring technology that is designed to provide an estimate of PCWP. A NIVA Score >18 indicated increased risk for 30-day hospital admission. This non-invasive measurement has potential for guiding decongestive therapy and prevention of hospital admission in heart failure patients.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 19 Sep 2021; epub ahead of print
Alvis B, Huston J, Schmeckpeper J, Polcz M, ... Hocking KM, Lindenfeld J
J Card Fail: 19 Sep 2021; epub ahead of print | PMID: 34555524
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Abstract

Trends in Heart Failure Hospitalizations in the US from 2008 to 2018.

Clark KAA, Reinhardt SW, Chouairi F, Miller PE, ... Ahmad T, Desai NR
Background
Heart failure (HF) is a major driver of health care costs in the United States and is increasing in prevalence. There is a paucity of contemporary data examining trends among hospitalizations for HF that specifically compare HF with reduced or preserved ejection fraction (HFrEF or HFpEF, respectively).
Methods and results
Using the National Inpatient Sample, we identified 11,692,995 hospitalizations due to HF. Hospitalizations increased from 1,060,540 in 2008 to 1,270,360 in 2018. Over time, the median age of patients hospitalized because of HF decreased from 76.0 to 73.0 years (P < 0.001). There were increases in the proportions of Black patients (18.4% in 2008 to 21.2% in 2018) and of Hispanic patients (7.1% in 2008 to 9.0% in 2018; P < 0.001, all). Over the study period, we saw an increase in comorbid diabetes, sleep apnea and obesity (P < 0.001, all) in the entire cohort with HF as well as in the HFrEF and HFpEF subgroups. Persons admitted because of HFpEF were more likely to be white and older compared to admissions because of HFrEF and also had lower costs. Inpatient mortality decreased from 2008 to 2018 for overall HF (3.3% to 2.6%) and HFpEF (2.4% to 2.1%; P < 0.001, all) but was stable for HFrEF (2.8%, both years). Hospital costs, adjusted for inflation, decreased in all 3 groups across the study period, whereas length of stay was relatively stable over time for all groups.
Conclusions
The volume of patients hospitalized due to HF has increased over time and across subgroups of ejection fraction. The demographics of HF, HFrEF and HFpEF have become more diverse over time, and hospital inpatient costs have decreased, regardless of HF type. Inpatient mortality rates improved for overall HF and HFpEF admissions but remained stable for HFrEF admissions.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 14 Sep 2021; epub ahead of print
Clark KAA, Reinhardt SW, Chouairi F, Miller PE, ... Ahmad T, Desai NR
J Card Fail: 14 Sep 2021; epub ahead of print | PMID: 34534665
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Abstract

The HEART Camp Exercise Intervention Improves Exercise Adherence, Physical Function, and Patient-Reported Outcomes in Adults With Preserved Ejection Fraction Heart Failure.

Alonso WW, Kupzyk KA, Norman JF, Lundgren SW, ... Keteyian SJ, Pozehl BJ
Background
Despite exercise being one of few strategies to improve outcomes for individuals with heart failure with preserved ejection fraction (HFpEF), exercise clinical trials in HFpEF are plagued by poor interventional adherence. Over the last 2 decades, our research team has developed, tested, and refined Heart failure Exercise And Resistance Training (HEART) Camp, a multicomponent behavioral intervention to promote adherence to exercise in HF. We evaluated the effects of this intervention designed to promote adherence to exercise in HF focusing on subgroups of participants with HFpEF and heart failure with reduced ejection fraction (HFrEF).
Methods and results
This randomized controlled trial included 204 adults with stable, chronic HF. Of those enrolled, 59 had HFpEF and 145 had HFrEF. We tested adherence to exercise (defined as ≥120 minutes of moderate-intensity [40%-80% of heart rate reserve] exercise per week validated with a heart rate monitor) at 6, 12, and 18 months. We also tested intervention effects on symptoms (Patient-Reported Outcomes Measurement Information System-29 and dyspnea-fatigue index), HF-related health status (Kansas City Cardiomyopathy Questionnaire), and physical function (6-minute walk test). Participants with HFpEF (n = 59) were a mean of 64.6 ± 9.3 years old, 54% male, and 46% non-White with a mean ejection fraction of 55 ± 6%. Participants with HFpEF in the HEART Camp intervention group had significantly greater adherence compared with enhanced usual care at both 12 (43% vs 14%, phi = 0.32, medium effect) and 18 months (56% vs 0%, phi = 0.67, large effect). HEART Camp significantly improved walking distance on the 6-minute walk test (η2 = 0.13, large effect) and the Kansas City Cardiomyopathy Questionnaire overall (η2 = 0.09, medium effect), clinical summary (η2 = 0.16, large effect), and total symptom (η2 = 0.14, large effect) scores. In the HFrEF subgroup, only patient-reported anxiety improved significantly in the intervention group.
Conclusions
A multicomponent, behavioral intervention is associated with improvements in long-term adherence to exercise, physical function, and patient-reported outcomes in adults with HFpEF and anxiety in HFrEF. Our results provide a strong rationale for a large HFpEF clinical trial to validate these findings and examine interventional mechanisms and delivery modes that may further promote adherence and improve clinical outcomes in this population.
Clinical trial registration
URL: https://clinicaltrials.gov/. Unique identifier: NCT01658670.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 14 Sep 2021; epub ahead of print
Alonso WW, Kupzyk KA, Norman JF, Lundgren SW, ... Keteyian SJ, Pozehl BJ
J Card Fail: 14 Sep 2021; epub ahead of print | PMID: 34534664
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Abstract

Subclinical Myocardial Injury and the Phenotype of Clinical Congestion in Patients With Heart Failure and Reduced Left Ventricular Ejection Fraction.

Thibodeau JT, Pham DD, Kelly SA, Ayers CR, ... Grodin JL, Drazner MH
Background
Clinical congestion is associated with adverse outcomes in patients with heart failure. The pathophysiological mediators of this association remain uncertain.
Methods and results
We prospectively enrolled a cohort of patients with heart failure and reduced left ventricular ejection fraction and performed a detailed clinical examination followed on the same day by an invasive right heart catheterization and blood sampling for biomarkers. High-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were measured. A clinical congestion score was calculated based on jugular venous pressure (cm H20 <10 = 0, 10-14 = 1, >14 = 2 points), bendopnea (0 vs 1), a third heart sound (0 vs 1), or peripheral edema (0-2). Congestion was categorized into tiers as absent (0 points), mild (1 point), or moderate to severe (≥ 2 points). We tested for associations of high-sensitivity troponin T, NT-proBNP, and elevated ventricular filling pressures with clinical congestion in both univariate and multivariable analyses. Of 153 participants, 65 (42%) had absent, 35 mild (23%), and 53 (35%) had moderate to severe clinical congestion. Congestion tier was associated with higher NT-proBNP and hs-troponin levels, and the right atrial pressure and pulmonary capillary wedge pressure (P < .001 for each). Increased congestion tier was also associated with the coexistent presence of elevated troponin T (≥52 ng/L), NT-proBNP (≥1000 pg/mL), and pulmonary capillary wedge pressure (≥22 mm Hg). Specifically, 78% of those with absent clinical congestion had 0 to 1 of these findings, whereas 75% of those with moderate-severe congestion had 2 or all 3 of these abnormalities (P < .001). An elevated hs-troponin was associated with mild or greater clinical congestion (odds ratio 3, 95% confidence interval 1.2-7.5, P = .02) in multivariable analysis adjusting for potential confounders including the right atrial pressure, pulmonary capillary wedge pressure, and NT-proBNP levels.
Conclusions
Clinical congestion is a phenotype in which there is a high coexistent presence of elevated ventricular filling pressures, elevated natriuretic peptide levels, and subclinical myocardial injury. An elevated troponin was associated with clinical congestion in multivariable models that adjusted for ventricular filling pressures and natriuretic peptide levels. These data strengthen the evidence base for an association of elevated troponin with clinical congestion, suggesting that subclinical myocardial injury may be an important contributor to the pathophysiology of the congested state.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 13 Sep 2021; epub ahead of print
Thibodeau JT, Pham DD, Kelly SA, Ayers CR, ... Grodin JL, Drazner MH
J Card Fail: 13 Sep 2021; epub ahead of print | PMID: 34534666
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Abstract

Policy and Payment Challenges in the Postpandemic Treatment of Heart Failure: Value-Based Care and Telehealth.

Piña IL, Allen LA, Desai NR
Increasing patient and therapeutic complexity have created both challenges and opportunities for heart failure care. Within this background, the coronavirus disease-2019 pandemic has disrupted care as usual, accelerating the need for transition from volume-based to value-based care, and demanding a rapid expansion of telehealth and remote care for heart failure. Patients, clinicians, health systems, and payors have by necessity become more invested in these issues. Herein we review recent changes in health care policy related to the movement from volume to value-based payment and from in-person to remote care delivery.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 10 Sep 2021; epub ahead of print
Piña IL, Allen LA, Desai NR
J Card Fail: 10 Sep 2021; epub ahead of print | PMID: 34520854
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Abstract

Temporal Trends in Post Myocardial Infarction Heart Failure and Outcomes among Older Adults.

Kochar A, Doll JA, Liang L, Curran J, Peterson ED
Objectives
To determine national trends and long term outcomes of post myocardial infarction (MI) heart failure.
Background
Myocardial infarction (MI) can be complicated by heart failure; there are limited data describing the contemporary patterns and clinical implications of post-MI heart failure.
Methods
We studied MI patients aged ≥ 65 years from 2000-2013 in a Medicare database. New onset heart failure post-MI was defined as either heart failure during index MI admission or a hospitalization for heart failure within 1 year of index MI event. A trend analysis of the incidence of heart failure was performed, differences were examined by Gray tests. The 5-year mortality rates were evaluated and differences among heart failure cohorts were ascertained by Gray tests.
Results
There were a total of 1,531,638 MI patients and 565,291 patients had heart failure (36.0%). The rate of heart failure during index admission was 32.3% and the frequency of heart failure hospitalization within 1 year was 10.4%. Patients with heart failure were older (81 vs 77 years). The temporal trend from 2001-2012 suggested a reduction in the incidence of heart failure during index admission (2001: 34.7%, 2012: 31.2%, p-trend < 0.01), as well as heart failure hospitalization within 1 year (2001: 11.3%, 2012: 8.7%, p-trend < 0.01). The 5-year mortality rate among patients without heart failure was 38.4% and for patients with any heart failure it was 68.7%.
Conclusion
Post-MI heart failure in older adults occurs in 1 in 3 patients within 1 year; heart failure portends significantly higher long-term mortality.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 10 Sep 2021; epub ahead of print
Kochar A, Doll JA, Liang L, Curran J, Peterson ED
J Card Fail: 10 Sep 2021; epub ahead of print | PMID: 34624511
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Abstract

The Incidence and Prevalence of Cardiac Amyloidosis in a Large Community-Based Cohort in Alberta, Canada.

Sepehrvand N, Youngson E, Fine N, Venner CP, ... Kaul P, Ezekowitz JA
Background
Despite the improved awareness of cardiac amyloidosis among clinicians, its incidence and prevalence is not well-described in a community setting. We sought to investigate the incidence and prevalence of cardiac amyloidosis in the community.
Methods and results
In the adult population of Alberta, we examined 3 cohorts: (1) probable cases of cardiac amyloidosis: the presence of physician-assigned diagnosis of amyloidosis (International Classification of Diseases [ICD]-10 code E85; ICD-9 277.3) and 1 or more health care encounter for heart failure (HF) (ICD-10 I50; ICD-9 428); (2) possible cardiac amyloidosis: the presence of clinical phenotypes suggestive of amyloidosis; and (3) a comparator HF cohort without amyloidosis. Between 2004 and 2018, 982 of the 145,329 patients with HF were identified as probable cardiac amyloidosis. During the same period, the incidence rates of probable cardiac amyloidosis increased from 1.38 to 3.69 per 100,000 person-years and the prevalence rates increased from 3.42 to 14.85 per 100,000 person-years (Ptrend < .0001). Patients with probable cardiac amyloidosis were more likely to be male, have a higher comorbidity burden, greater health care use, and poorer outcomes as compared with patients with HF without amyloidosis. A much larger group of patients was identified as possible cardiac amyloidosis (n = 46,255), with similar increase in prevalence from 2004 to 2018 (from 416 to 850 per 100,000 person-years).
Conclusions
The incidence and prevalence of cardiac amyloidosis has increased over the last decade. Given the advent of new therapies for cardiac amyloidosis and considering their high cost, it is imperative to devise strategies to screen, identify, and track patients with cardiac amyloidosis from administrative databases.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 08 Sep 2021; epub ahead of print
Sepehrvand N, Youngson E, Fine N, Venner CP, ... Kaul P, Ezekowitz JA
J Card Fail: 08 Sep 2021; epub ahead of print | PMID: 34509599
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Abstract

Contemporary Nationwide Heart Transplantation and Left Ventricular Assist Device Outcomes in Patients with Histories of Bariatric Surgery.

Hirji SA, Sabatino ME, Minhas AMK, Okoh AK, ... Vaduganathan M, Khan MS
Bariatric surgery may play a role in the management of morbidly obese patients with end-stage heart failure through increasing eligibility and improving the outcomes of destination therapies. We conducted a nationally representative, retrospective cohort study of patients with previous bariatric surgery undergoing either heart transplantation or left ventricular assist device implantation. Of 200 patients, < 6% experienced in-hospital mortality after destination therapy, comparable to that reported in the general population of heart recipients. Risk-adjusted outcomes differed minimally from those of obese patients undergoing destination therapy without previous bariatric surgery. This study provides important safety benchmarking data and demonstrates the feasibility of bariatric surgery as a potential bridge to left ventricular assist device implantation or heart transplantation in obese patients with end-stage heart failure.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 08 Sep 2021; epub ahead of print
Hirji SA, Sabatino ME, Minhas AMK, Okoh AK, ... Vaduganathan M, Khan MS
J Card Fail: 08 Sep 2021; epub ahead of print | PMID: 34509598
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Abstract

Pretransplant Right Ventricular Dysfunction Is Associated With Increased Mortality After Heart Transplantation: A Hard Inheritance to Overcome.

Bellettini M, Frea S, Pidello S, Boffini M, ... Potena L, De Ferrari GM
Background
Right ventricular dysfunction (RVD) is a major issue in patients with advanced heart failure because it precludes the implantation of left ventricular assist device, usually leaving heart transplantation (HTx) as the only available treatment option. The pulmonary artery pulsatility index (PAPi) is a hemodynamic parameter integrating information of right ventricular function and of pulmonary circulation. Our aim is to evaluate the association of preoperative RVD, hemodynamically defined as a low PAPi, with post-HTx survival.
Methods and results
Consecutive adult HTx recipient at 2 Italian transplant centers between 2000 and 2018 with available data on pre-HTx right heart catheterization were included retrospectively. RVD was defined as a value of PAPi lower than the 25th percentile of the study population. The association of RVD with the 1-year post-HTx mortality and other secondary end points were evaluated. Multivariate logistic regression was used to adjust for clinical and hemodynamic variables. Analyses stratified by pulmonary vascular resistance (PVR) status (≥3 Woods units vs <3 Woods units) were also performed. Among 657 HTx recipients (female 31.1%, age 53 ± 11 years), patients with pre-HTx RVD (PAPi of <1.68) had significantly lower 1-year survival rates (77.8% vs 87.1%, P = .005), also after adjusting for estimated glomerular filtration rate, total bilirubin, PVR, serum sodium, inotropes, and mechanical circulatory support at HTx (hazard ratio 2.0, 95% confidence interval, 1.3-3.1). RVD was also associated with post-HTx renal replacement therapy (hazard ratio 2.0, 95% confidence interval 1.05-3.30) and primary graft dysfunction (hazard ratio 1.7, , 95% confidence interval 1.02-3.30). When stratifying patients by estimated PVR status, RVD was associated with worse 1-year survival among patients with normal PVR (76.9% vs 88.3%, P = .003), but not in those with increased PVR (78.6% vs 83.2%, P = .49).
Conclusions
Preoperative RVD, evaluated through PAPi, is associated with mortality and morbidity after HTx, providing incremental prognostic value over traditional clinical and hemodynamic parameters.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 08 Sep 2021; epub ahead of print
Bellettini M, Frea S, Pidello S, Boffini M, ... Potena L, De Ferrari GM
J Card Fail: 08 Sep 2021; epub ahead of print | PMID: 34509597
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Abstract

Renal Hemodynamics and Renin-Angiotensin-Aldosterone System Profiles in Patients With Heart Failure.

Lytvyn Y, Burns KD, Testani JM, Lytvyn A, ... Cherney DZI, Parker JD
Objective
Understanding cardiorenal pathophysiology in heart failure (HF) is of clinical importance. We sought to characterize the renal hemodynamic function and the transrenal gradient of the renin-angiotensin-aldosterone system (RAAS) markers in patients with HF and in controls without HF.
Methods
In this post hoc analysis, the glomerular filtration rate (GFRinulin), effective renal plasma flow (ERPFPAH) and transrenal gradients (arterial-renal vein) of angiotensin converting enzyme (ACE), aldosterone, and plasma renin activity (PRA) were measured in 47 patients with HF and in 24 controls. Gomez equations were used to derive afferent (RA) and efferent (RE) arteriolar resistances. Transrenal RAAS gradients were also collected in patients treated with intravenous dobutamine (HF, n = 11; non-HF, n = 11) or nitroprusside (HF, n = 18; non-HF, n = 5).
Results
The concentrations of PRA, aldosterone and ACE were higher in the renal vein vs the artery in patients with HF vs patients without HF (P < 0.01). In patients with HF, a greater ACE gradient was associated with greater renal vascular resistance (r = 0.42; P 0.007) and greater arteriolar resistances (RA: r = 0.39; P = 0.012; RE: r = 0.48; P = 0.002). Similarly, a greater aldosterone gradient was associated with lower GFR (r = -0.51; P = 0.0007) and renal blood flow (RBF), r = -0.32; P = 0.042) whereas greater PRA gradient with lower ERPF (r = -0.33; P = 0.040), GFR (r = -0.36; P = 0.024), and RBF (r = -0.33; P = 0.036). Dobutamine and nitroprusside treatment decreased the transrenal gradient of ACE (P = 0.012, P < 0.0001, respectively), aldosterone (P = 0.005, P = 0.030) and PRA (P = 0.014, P = 0.002) in patients with HF only.
Conclusions
A larger transrenal RAAS marker gradient in patients with HF suggests a renal origin for neurohormonal activation associated with a vasoconstrictive renal profile.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 03 Sep 2021; epub ahead of print
Lytvyn Y, Burns KD, Testani JM, Lytvyn A, ... Cherney DZI, Parker JD
J Card Fail: 03 Sep 2021; epub ahead of print | PMID: 34487814
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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: 30 Aug 2021; 27:942-948
Lekavich CL, Abraham D, Fudim M, Green C, ... Barksdale D, Kraus WE
J Card Fail: 30 Aug 2021; 27:942-948 | PMID: 33965536
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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: 30 Aug 2021; 27:1031-1033
Kagami K, Takemura M, Yoshida K, Harada T, ... Kurabayashi M, Obokata M
J Card Fail: 30 Aug 2021; 27:1031-1033 | PMID: 33965537
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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: 30 Aug 2021; 27:991-1001
Brener MI, Hamid NB, Fried JA, Masoumi A, ... Uriel N, Burkhoff D
J Card Fail: 30 Aug 2021; 27:991-1001 | PMID: 33989781
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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: 30 Aug 2021; 27:1002-1016
Cosiano MF, Tobin R, Mentz RJ, Greene SJ
J Card Fail: 30 Aug 2021; 27:1002-1016 | PMID: 33991684
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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: 30 Aug 2021; 27:925-933
Wong CW, Tafuro J, Azam Z, Satchithananda D, ... Mallen C, Kwok CS
J Card Fail: 30 Aug 2021; 27:925-933 | PMID: 34048921
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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: 30 Aug 2021; 27:965-973
Weissman GE, Teeple S, Eneanya ND, Hubbard RA, Kangovi S
J Card Fail: 30 Aug 2021; 27:965-973 | PMID: 34048918
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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: 30 Aug 2021; 27:934-941
Julius FEC, VAN Norel MR, Zandijk AJL, Rathwell S, ... Voors AA, Ezekowitz JA
J Card Fail: 30 Aug 2021; 27:934-941 | PMID: 34048917
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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: 30 Aug 2021; 27:981-990
Ferraro RA, Ogunmoroti O, Zhao D, Ndumele CE, ... Bielinski SJ, Michos ED
J Card Fail: 30 Aug 2021; 27:981-990 | PMID: 34051347
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Impact:
Abstract

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

Rao A, Anderson KM, Mohammed S, Hofmeyer M, ... Najjar SS, Groninger H
Background
Many patients with American College of Cardiology/American Heart Association Stage D (advanced) heart failure 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 who were 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 with palliative care.
Results
Overall, patients received CIIS therapy for an average of 5.9 months (standard deviation [SD] 7.3). Patients on CIIS as palliative therapy died in 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 for 6.2 months, on average, with wide variation among patients. Patients who were on CIIS as bridge therapy but did not ultimately receive surgical therapy received less palliative care despite the high mortality rate in this subgroup.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 Aug 2021; 27:974-980
Rao A, Anderson KM, Mohammed S, Hofmeyer M, ... Najjar SS, Groninger H
J Card Fail: 30 Aug 2021; 27:974-980 | PMID: 34153459
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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
Previous studies have demonstrated that children in the United States who were of 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 use remains unknown.
Methods
All children (age <18 years) in the Scientific Registry of Transplant Recipients database listed for HT from December 2011 to February 2019 were included and were separated into 5 races/ethnicities: Caucasian, African American, Hispanic, Asian, and Other. Differences in clinical characteristics and survival among 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%), whereas Caucasian children had congenital heart disease (58.7%). African American children were most likely to be listed as Status 1A and to have renal dysfunction and hypoalbuminemia at listing. African American and Hispanic children were most likely to be on Medicaid. After multivariable analysis, it was found that only African American children were at increased risk for waitlist mortality as compared to Caucasian children (adjusted hazard ratio = 1.25; P = 0.029). Post-HT, there were no disparities in early and midterm graft survival among groups, but African American children had increased numbers 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 health care access and implicit bias as reasons for these disparities need to be conducted.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 Aug 2021; 27:957-964
Amdani S, Bhimani SA, Boyle G, Liu W, ... Saarel E, Hsich E
J Card Fail: 30 Aug 2021; 27:957-964 | PMID: 34139364
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Impact:
Abstract

Characteristics and Outcomes of Patients with Inflammatory Cardiomyopathies Receiving Mechanical Circulatory Support: An STS-Intermacs Registry Analysis.

Sheikh FH, Craig PE, Ahmed S, Torguson R, ... Najjar SS, Mohammed SF
Background
Durable mechanical circulatory support therapy (MCS) improves survival in patients with advanced heart failure. Knowledge regarding the outcomes experienced by inflammatory cardiomyopathy patients who receive durable MCS therapy is limited.
Methods
We compared patients with inflammatory cardiomyopathy to idiopathic dilated cardiomyopathy (IDCM) patients enrolled in the STS-Intermacs registry.
Results
Among 19,012 patients, 329 (1.7%) had inflammatory cardiomyopathy, whereas 5,978 had IDCM (31.4%). The inflammatory cardiomyopathy patients were younger, more likely to be white, and women. These patients experienced more pre-operative arrhythmias and higher use of temporary MCS. Inflammatory cardiomyopathy patients had a higher rate of early adverse events (<3 months post-device implant) including bleeding, arrhythmias, non-device related infections, neurological dysfunction, and respiratory failure.  The rate of late adverse events (≥ 3 months) was similar in the 2 groups. Inflammatory cardiomyopathy patients had a similar 1-year (80% vs 84%) and 2-year (72% VS 76%, P=0.15) survival. Myocardial recovery resulting in device explant was more common among inflammatory cardiomyopathy patients (5.5% vs. 2.3%, p < 0.001).
Conclusion
Inflammatory cardiomyopathy patients who received durable MCS appear to have similar survival compared to idiopathic dilated cardiomyopathy patients despite a higher early adverse event burden. Our findings support the use of durable MCS in an inflammatory cardiomyopathy population.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 29 Aug 2021; epub ahead of print
Sheikh FH, Craig PE, Ahmed S, Torguson R, ... Najjar SS, Mohammed SF
J Card Fail: 29 Aug 2021; epub ahead of print | PMID: 34474157
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Impact:
Abstract

The Relationship Between Valproate and Lamotrigine/Levetiracetam Use and Prognosis in Patients With Epilepsy and Heart Failure: A Danish Register-Based Study.

Liang D, Gardella E, Kragholm K, Polcwiartek C, Sessa M
Objective
To compare the hazard for all-cause mortality and mortality due to heart failure (HF) between valproate (VPA) and levetiracetam (LEV)/lamotrigine (LTG) users in patients aged ≥ 65 with comorbidities of epilepsy and HF.
Methods
This was a cohort study using Danish registers during the period from January 1996 to July 2018. The study population included new users of LTG, LEV or VPA. A Cox regression model was used to compute crude and adjusted hazard ratios for the outcome, using an intention-to-treat approach. Average treatment effects (eg, 1-year absolute risks), risk differences and the ratio of risks were computed using the G-formula based on a Cox regression model for the outcomes at the end of the follow-up period.
Results
We included 1345 subjects in the study population. VPA users (n = 696), when compared to LTG/LEV users (n = 649), had an increased hazard of mortality due to HF (hazard ratio [HR] 2.39; 95% CI 1.02-5.60) and to all-cause mortality (HR 1.37; 95% CI 1.01-1.85) in both crude and adjusted analyses. The 1-year absolute risks for all-cause mortality were 29% (95% CI 25%-33%) and 22% (95% CI 18%-26%) for VPA and LTG/LEV users. For mortality due to HF, 1-year absolute risks were 5% (95% CI 3%-7%) and 2% (95% CI 1%-4%) for VPA and LTG/LEV users. The average risk ratio, with LTG/LEV as the reference group, was 1.31 (95% CI 1.02-1.71) for all-cause mortality and 2.35 (95% CI 1.11-5.76) for HF mortality.
Conclusion
In older people with HF and epilepsy, treatment with VPA was associated with a higher risk of all-cause and HF mortality compared to treatment with LTG and LEV.

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

J Card Fail: 23 Aug 2021; epub ahead of print
Liang D, Gardella E, Kragholm K, Polcwiartek C, Sessa M
J Card Fail: 23 Aug 2021; epub ahead of print | PMID: 34438055
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Impact:
Abstract

Effect of Empagliflozin Versus Placebo on Body Fluid Balance in Patients With Acute Myocardial Infarction and Type 2 Diabetes Mellitus: Subgroup Analysis of the EMBODY Trial.

Hoshika Y, Kubota Y, Mozawa K, Tara S, ... Tanabe J, Shimizu W
Background
The development of heart failure is associated with fluid balance, including that of extracellular water (ECW) and intracellular water (ICW). This study determined whether sodium-glucose cotransporter 2 inhibitors affect fluid balance and improve heart failure in patients after acute myocardial infarction.
Methods and results
EMBODY was a prospective, randomized, double-blinded, placebo-controlled trial of Japanese patients with acute myocardial infarction and type 2 diabetes. Overall, 55 patients who underwent bioelectrical impedance analysis were randomized to receive once daily 10 mg empagliflozin or placebo 2 weeks after acute myocardial infarction onset. We investigated the time course of body fluid balance measured using the bioelectrical impedance analysis device, InBody. The primary end points were changes in body fluid balance from weeks 0 to 24. Changes between baseline and week 24 in the empagliflozin and placebo groups were -0.21 L (P = .127) and +0.40 L (P = .001) in ECW (P = .001) and -0.23 L (P = .264) and +0.74 L (P < .001) in ICW (P < .001), respectively. In a stratified analysis, the rise in ECW and ICW was significantly attenuated in the empagliflozin group in contrast to the placebo group in participants with a body mass index of 25 or higher but not in those with a body mass index of less than 25.
Conclusions
Early sodium-glucose cotransporter 2 inhibitor administration may attenuate changes in ECW and ICW.

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

J Card Fail: 20 Aug 2021; epub ahead of print
Hoshika Y, Kubota Y, Mozawa K, Tara S, ... Tanabe J, Shimizu W
J Card Fail: 20 Aug 2021; epub ahead of print | PMID: 34425223
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Impact:
Abstract

Survival Association of Angiotensin Inhibitors in Heart Failure With Reduced Ejection Fraction: Comparisons Using Self-Identified Race and Genomic Ancestry.

Luzum JA, Edokobi O, Dorsch MP, Peterson E, ... Williams LK, Lanfear DE
Background
It remains unclear whether there is a racial disparity in the response to angiotensin inhibitors in patients with heart failure with reduced ejection fraction (HFrEF) and whether the role of genomic ancestry plays a part. Therefore, we compared survival rates associated with angiotensin inhibitors in patients with HFrEF by self-identified race and proportion of West African genomic ancestry.
Methods
Three datasets totaling 1153 and 1480 self-identified Black and White patients, respectively, with HFrEF were meta-analyzed (random effects model) for race-based analyses. One dataset had genomic data for ancestry analyses (416 and 369 self-identified Black and White patients, respectively). Cox proportional hazards regression, adjusted for propensity scores, assessed the association of angiotensin inhibitor exposure with all-cause mortality by self-identified race or proportion of West African genomic ancestry.
Results
In meta-analysis of self-identified race, adjusted hazard ratios (95% CI) for exposure to angiotensin inhibitors were similar in self-identified Black and White patients with HFrEF: 0.52 (0.31-0.85) P = 0.006 and 0.54 (0.42-0.71) P = 0.001, respectively. Results were similar when the proportion of West African genomic ancestry was > 80% or < 5%: 0.66 (0.34-1.25) P = 0.200 and 0.56 (0.26-1.23) P = 0.147, respectively.
Conclusions
Among self-identified Black and White patients with HFrEF, reduction in all-cause mortality associated with exposure to angiotensin inhibitors was similar regardless of self-identified race or proportion of West African genomic ancestry.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 20 Aug 2021; epub ahead of print
Luzum JA, Edokobi O, Dorsch MP, Peterson E, ... Williams LK, Lanfear DE
J Card Fail: 20 Aug 2021; epub ahead of print | PMID: 34425222
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Impact:
Abstract

Sleep Outcomes From AWAKE-HF: A Randomized Clinical Trial of Sacubitril/Valsartan vs Enalapril in Patients With Heart Failure and Reduced Ejection Fraction.

Owens RL, Birkeland K, Heywood JT, Steinhubl SR, ... Fombu E, Khandwalla R
Background
Heart failure and sleep-disordered breathing have been increasingly recognized as co-occurring conditions. Their bidirectional relationship warrants investigation into whether heart failure therapy improves sleep and sleep-disordered breathing. We sought to explore the effect of treatment with sacubitril/valsartan on sleep-related endpoints from the AWAKE-HF study.
Methods and results
AWAKE-HF was a randomized, double-blind study conducted in 23 centers in the United States. Study participants with heart failure with reduced rejection fraction and New York Heart Association class II or III symptoms were randomly assigned to receive treatment with either sacubitril/valsartan or enalapril. All endpoints were assessed at baseline and after 8 weeks of treatment. Portable sleep-monitoring equipment was used to measure the apnea-hypopnea index, including obstructive and central events. Total sleep time, wake after sleep onset and sleep efficiency were exploratory measures assessed using wrist actigraphy.
The results were as follows
140 patients received treatment in the double-blind phase (sacubitril/valsartan, n = 70; enalapril, n = 70). At baseline, 39% and 40% of patients randomly assigned to receive sacubitril/valsartan or enalapril, respectively, presented with undiagnosed, untreated, moderate-to-severe sleep-disordered breathing (≥ 15 events/h), and nearly all had obstructive sleep apnea. After 8 weeks of treatment, the mean 4% apnea-hypopnea index changed minimally from 16.3/h to 15.2/h in the sacubitril/valsartan group and from 16.8/h to 17.6/h in the enalapril group. Mean total sleep time was long at baseline and decreased only slightly in both treatment groups at week 8 (-14 and -11 minutes for sacubitril/valsartan and enalapril, respectively), with small changes in wake after sleep onset and sleep efficiency in both groups.
Conclusions
In a cohort of patients with heart failure with reduced rejection fraction who met prescribing guidelines for sacubitril/valsartan, one-third had undiagnosed moderate-to-severe obstructive sleep apnea. The addition of sacubitril/valsartan therapy did not significantly improve sleep-disordered breathing or sleep duration or efficiency. Patients who meet indications for treatment with sacubitril/valsartan should be evaluated for sleep-disordered breathing.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 20 Aug 2021; epub ahead of print
Owens RL, Birkeland K, Heywood JT, Steinhubl SR, ... Fombu E, Khandwalla R
J Card Fail: 20 Aug 2021; epub ahead of print | PMID: 34428592
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Impact:
Abstract

Treatment Persistence of Renin-Angiotensin-Aldosterone-System Inhibitors over Time in Heart Failure with Reduced Ejection Fraction.

Vaduganathan M, Fonarow GC, Greene SJ, DeVore AD, ... Hernandez AF, Butler J
Background
Clinical practice guidelines support sustained use of renin-angiotensin-aldosterone-system (RAAS) inhibitors over time in heart failure with reduced ejection fraction, yet few data are available regarding frequency, timing, and predictors of early treatment discontinuation in clinical practice.
Methods
Among prevalent or new users of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitors (ARNI), and mineralocorticoid receptor antagonists (MRAs) in the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, we estimated the frequency and independent predictors of treatment discontinuation during follow-up. Among sites with >5 users of a given RAAS inhibitor, we evaluated practice variation in the proportion of patients with treatment discontinuation.
Results
Over median follow-up of 18 months, frequency of drug discontinuation of ACEi/ARB, ARNI, and MRA was 12.7% (444 of 3,509 users), 10.4% (140 of 1,352 users), and 20.4% (435 of 2,129 users), respectively. An additional, 149 (11.0%) of ARNI users were switched to ACEi/ARB and 447 (12.7%) ACEi/ARB users were switched to ARNI during follow-up. Across sites, the median proportion of discontinuation of ACEi/ARB, ARNI, and MRA was 12.5% (25th-75th percentiles 6.9-18.9%), 18.8% (25th-75th percentiles 12.5-28.6%), and 19.6% (25th-75th percentiles 10.7-27.0%), respectively. Chronic kidney disease was the only independent predictor of increased risk of discontinuation of each of the RAAS inhibitor classes (P<0.02 for all). Higher Kansas City Cardiomyopathy Questionnaire overall summary scores independently predicted lower risk of discontinuation of ACEi/ARB and ARNI (both P<0.001), but not MRA. Investigator clinical experience was predictive of lower risks of discontinuation of ACEi/ARB and MRA (P<0.02), but not ARNI. All other independent predictors of discontinuation were unique to individual therapeutic classes.
Conclusions
One in 10 patients discontinue ACEi/ARB or ARNI and 1 in 5 discontinue MRA in routine clinical practice of HFrEF. Unique patient-level and clinician/practice-level factors are associated with premature discontinuation of individual RAAS inhibitors, which may help to guide structured efforts to promote treatment persistence in clinical care.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 20 Aug 2021; epub ahead of print
Vaduganathan M, Fonarow GC, Greene SJ, DeVore AD, ... Hernandez AF, Butler J
J Card Fail: 20 Aug 2021; epub ahead of print | PMID: 34428591
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Impact:
Abstract

Postdischarge Functional Capacity, Health-Related Quality of Life, Depression, Anxiety, and Post-traumatic Stress Disorder in Patients Receiving a Long-term Left Ventricular Assist Device.

Sladen RN, Shulman MA, Javaid A, Hodgson C, ... Yozefpolskaya M, Colombo PC
Background
There is a paucity of data on depression, anxiety and post-traumatic stress disorder after left ventricular assist device (LVAD) implantation. We designed an observational study to integrate these with functional capacity and health-related quality of life (HR-QOL) in surviving LVAD patients.
Methods and results
Consenting patients between 1 month and 9 years after LVAD implantation (n = 121) were screened for functional capacity (World Health Organization Disability Assessment Schedule 2.0 [WHODAS 2.0)]); HR-QOL (European Quality of Life [EQ-5D] and Visual Assessment Scales [EQ-VAS]), depression (Patient Health Questionnaire [PHQ-9], anxiety (Generalized Anxiety Disorder Scale [GAD-7]) and post-traumatic stress disorder (Impact of Event Scale Revised [IES-R]). Of the 94% of patients who consented, 34.7% reported impaired functional capacity (WHODAS 2.0 score of ≥25%), 23.1%-34.7% HR-QOL problems (domain EQ-5D of ≥3), 10.7% \"poor health\" (EQ-VAS of ≤40), 14.9% depression (PHQ-9 of >14), 11.7% suicidal ideation and 17.5% anxiety (GAD-7 of >10). Among these patients, 23.5% had a positive screen for post-traumatic stress disorder (IES-R of ≥24). An EQ-VAS of 80 or greater predicted good functional capacity (P < .001).
Conclusions
One-third of discharged LVAD patients reported impaired function, HR-QOL, and psychological issues. A standardized evaluation before and after LVAD implantation could facilitate psychologic prehabilitation, inform decision-making, and identify indications for mental health intervention.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 19 Aug 2021; epub ahead of print
Sladen RN, Shulman MA, Javaid A, Hodgson C, ... Yozefpolskaya M, Colombo PC
J Card Fail: 19 Aug 2021; epub ahead of print | PMID: 34425221
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Impact:
Abstract

Prevalence, Temporal Change, and Determinants of Anxiety and Depression in Hospitalized Patients With Heart Failure.

Hamatani Y, Iguchi M, Ikeyama Y, Kunugida A, ... Nakashima Y, Akao M
Background
Anxiety and depression may be under-recognized in patients with heart failure (HF). We therefore investigated the prevalence and temporal change of these symptoms in hospitalized patients with HF.
Methods and results
We prospectively evaluated consecutive hospitalized patients with HF using the Hospital Anxiety and Depression Scale (HADS) on admission and at discharge. The HADS-A (anxiety) and HADS-D (depression) scores were categorized as follows; 0-7, no symptoms; 8-10, mild; and 11-21, significant anxiety or depression. Symptom worsening was defined as the HADS category at discharge being poorer than that on admission. Of 224 patients (mean age 77.5 years), 35 (16%) and 62 (28%) had significant symptoms of anxiety and depression, respectively. During hospitalization, the HADS-A significantly decreased (on admission; median 6 [interquartile range (IQR) 3-9] vs at discharge; median 4 [IQR 2-7], P < .01), whereas the HADS-D did not improve (on admission; median 8 [IQR 5-11] vs at discharge; median 8 [IQR 4-11], P =.82). Anxiety and depression worsened during hospitalization in 19 (10%) and 40 (21%) patients, respectively. Advanced age, higher natriuretic peptide levels, and acute-on-chronic HF were associated with worsening anxiety, and longer hospitalization length was associated with worsening depression.
Conclusions
Anxiety and depression were common and depression persisted during HF hospitalization.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 19 Aug 2021; epub ahead of print
Hamatani Y, Iguchi M, Ikeyama Y, Kunugida A, ... Nakashima Y, Akao M
J Card Fail: 19 Aug 2021; epub ahead of print | PMID: 34419596
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Abstract

Role of Internal Jugular Venous Ultrasound in suspected or confirmed Heart Failure: A Systematic Review.

Chaudhary R, Sukhi A, Simon MA, Villanueva FS, Pacella JJ
Background
Few data are available on the use of internal jugular vein (IJV) ultrasound parameters to assess central venous pressure and clinical outcomes among patients with suspected or confirmed heart failure (HF).
Methods
We performed electronic searches on PubMed, The Cochrane Library, EMBASE, EBSCO, Web of Science, and CINAHL databases from the inception through January 9, 2021, to identify studies evaluating the accuracy and reliability of the IJV ultrasound parameters and exploring its correlation with central venous pressure and clinical outcomes in adult patients with suspected or confirmed acutely decompensated HF. The studies\' report quality was assessed by Quality Assessment of Diagnostic Accuracy Studies-2 scale.
Results
A total of 11 studies were eligible for final analysis (n = 1481 patients with HF). The studies were segregated into 3 groups: (1) the evaluation of patients presenting to the emergency department with dyspnea, (2) the evaluation of patients presenting to the HF clinic for follow-up, and (3) the evaluation of hospitalized patients with acutely decompensated HF or undergoing right heart catheterization. US parameters included IJV height, IJV diameter, IJV diameter ratio, IJV cross-sectional area, respiratory compressibility index, and compression compressibility index.
Conclusions
The findings of this systematic review suggest a significant role for ultrasound interrogation of the IJV in evaluation of patients in the emergency department presenting with dyspnea, in the outpatient clinic for poor clinical outcomes in HF, and in determining the timing of discharge for patients admitted with acutely decompensated HF. Further studies are warranted for testing the reliability of the reported ultrasound indices.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 18 Aug 2021; epub ahead of print
Chaudhary R, Sukhi A, Simon MA, Villanueva FS, Pacella JJ
J Card Fail: 18 Aug 2021; epub ahead of print | PMID: 34419599
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Impact:
Abstract

Right Ventricular Ejection Fraction and Beta-Blocker Effect in Heart Failure With Reduced Ejection Fraction.

Lam PH, Keramida K, Filippatos GS, Gupta N, ... Fonarow GC, Ahmed A
Background
A low right ventricular ejection fraction (RVEF) is a marker of poor outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Beta-blockers improve outcomes in HFrEF, but whether this effect is modified by RVEF is unknown.
Methods and results
Of the 2798 patients in Beta-Blocker Evaluation of Survival Trial (BEST), 2008 had data on baseline RVEF (mean 35%, median 34%). Patients were categorized into an RVEF of less than 35% (n = 1012) and an RVEF of 35% or greater (n = 996). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) within each RVEF subgroup and formally tested for interactions between bucindolol and RVEF. The effect of bucindolol on all-cause mortality in 2008 patients with baseline RVEF (HR 0.88, 95% CI 0.75-1.02) is consistent with that in 2798 patients in the main trial (HR 0.90, 95% CI 0.78-1.02). Bucindolol use was associated with a lower risk of all-cause mortality in patients with an RVEF of 35% or greater (HR 0.70, 95% CI 0.55-0.89), but not in those with an RVEF of less than 35% (HR 1.02, 95% CI 0.83-1.24, P for interaction = .022). Similar variations were observed for cardiovascular mortality (P for interaction = .009) and sudden cardiac death (P for interaction = .018), but not for pump failure death (P for interaction = .371) or HF hospitalization (P for interaction = .251).
Conclusions
The effect of bucindolol on mortality in patients with HFrEF was modified by the baseline RVEF. If these hypothesis-generating findings can be replicated using approved beta-blockers in contemporary patients with HFrEF, then RVEF may help to risk stratify patients with HFrEF for optimization of beta-blocker therapy.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 18 Aug 2021; epub ahead of print
Lam PH, Keramida K, Filippatos GS, Gupta N, ... Fonarow GC, Ahmed A
J Card Fail: 18 Aug 2021; epub ahead of print | PMID: 34419597
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Impact:
Abstract

EXPANDing the Donor Pool: Quantifying the Potential Impact of a Portable Organ-Care System for Expanded Criteria Heart Donation.

Jawitz OK, Devore AD, Patel CB, Bryner BS, Schroder JN
The recently concluded prospective Portable Organ Care System (OCS) Heart trial to Evaluate the Safety and Effectiveness of The Portable Organ Care System Heart for Preserving and Assessing Expanded Criteria Donor Hearts for Transplantation (EXPAND) demonstrated that the use of ex vivo perfusion for expanded-criteria hearts may be a viable method for increasing the use of donor hearts. We sought to estimate the potential impact of ex vivo expanded-criteria heart perfusion on the donor pool in the United States by using a large national transplant registry. After applying the inclusion criteria of EXPAND, 8637 potentially eligible donors were identified in the U.S. between January 1, 2015, and June 30, 2019, representing a substantial potential increase in the donor pool.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 14 Aug 2021; epub ahead of print
Jawitz OK, Devore AD, Patel CB, Bryner BS, Schroder JN
J Card Fail: 14 Aug 2021; epub ahead of print | PMID: 34407451
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Impact:
Abstract

Multinephron Segment Diuretic Therapy to Overcome Diuretic Resistance in Acute Heart Failure: A Single-Center Experience.

Cox ZL, Sarrell BA, Cella MK, Tucker B, ... Lewis JB, Dwyer JP
Background
The concept of multinephron segment diuretic therapy (MSDT) has been recommended in severe diuretic resistance with only expert opinion and case-level evidence. The purpose of this study was to investigate the safety and efficacy of MSDT, combining 4 diuretic classes, in acute heart failure (AHF) complicated by diuretic resistance.
Methods and results
A retrospective analysis was conducted in patients hospitalized with AHF at a single medical center who received MSDT, including concomitant carbonic anhydrase inhibitor, loop, thiazide, and mineralocorticoid receptor antagonist diuretics. Subjects served as their own controls with efficacy evaluated as urine output and weight change before and after MSDT. Serum chemistries, renal replacement therapies, and in-hospital mortality were evaluated for safety. Patients with severe diuretic resistance before MSDT were analyzed as a subcohort. A total of 167 patients with AHF and diuretic resistance received MSDT. MSDT was associated with increased median 24-hour urine output in the first day of therapy compared with the previous day (2.16 L [0.95-4.14 L] to 3.08 L [1.74-4.86 L], P = .003) in the total cohort and in the Severe diuretic resistance cohort (0.91 L [0.43-1.43 L] to 2.08 L [1.13-3.96 L], P < .001). The median cumulative weight loss at day 7 or discharge was -7.4 kg (-15.3 to -3.4 kg) (P = .02). Neither serum sodium, chloride, potassium, bicarbonate, or creatinine changed significantly relative to baseline (P > .05 for all).
Conclusions
In an AHF cohort with diuretic resistance, MSDT was associated with increased diuresis without changes in serum chemistries or kidney function. Prospective studies of MSDT in AHF and diuretic resistance are warranted.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 13 Aug 2021; epub ahead of print
Cox ZL, Sarrell BA, Cella MK, Tucker B, ... Lewis JB, Dwyer JP
J Card Fail: 13 Aug 2021; epub ahead of print | PMID: 34403831
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Impact:
Abstract

Hemodynamics for the Heart Failure Clinician: A State-of-the-Art Review.

Hsu S, Fang JC, Borlaug BA
Heart failure (HF) fundamentally reflects an inability of the heart to provide adequate blood flow to the body without incurring the cost of increased cardiac filling pressures. This failure occurs first during the stressed state, but progresses until hemodynamic derangements become apparent at rest. As such, the measurement and interpretation of both resting and stressed hemodynamics serve an integral role in the practice of the HF clinician. In this review, we discuss conceptual and technical best practices in the performance and interpretation of both resting and invasive exercise hemodynamic catheterization, relate important pathophysiologic concepts to clinical care, and discuss updated, evidence-based applications of hemodynamics as they pertain to the full spectrum of HF conditions.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 09 Aug 2021; epub ahead of print
Hsu S, Fang JC, Borlaug BA
J Card Fail: 09 Aug 2021; epub ahead of print | PMID: 34389460
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Impact:
Abstract

New Drugs for Heart Failure: What is the Evidence in Older Patients?

Orso F, Herbst A, Pratesi A, Fattirolli F, ... Marchionni N, Baldasseroni S
Heart failure (HF) is a major public health concern, with a high prevalence in the older population. The majority of randomized clinical trials evaluating new emerging pharmacologic agents for HF (eg, angiotensin receptor-neprilysin inhibitors, sodium-glucose cotransporter 2 inhibitors, intravenous iron for deficiency treatment, transthyretin stabilizers, soluble guanylate cyclase stimulators, cardiac myosin activators, and new potassium binders) have found positive results on various clinical outcomes, particularly in patients with reduced ejection fraction. These treatments might have an important role in the management of older patients as well. Nevertheless, trials demonstrating benefit of these drugs have involved patients significantly younger (on average, approximately 10 years) and fewer comorbidities than those commonly encountered in clinical practice. We describe the recent evidence regarding the newest HF drugs and their applicability to older individuals in terms of efficacy and safety, and we discuss their effects on outcomes particularly valuable to older patients, such as preservation of cognitive function, functional status, independence, and quality of life. Although available subgroup analyses seem to confirm efficacy and safety across the age spectrum for some of these drugs, their effects on older patients centered outcomes often have been neglected. Future HF trials should be designed to include older patients more representative of the real clinical practice, to overcome generalizability biases.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 03 Aug 2021; epub ahead of print
Orso F, Herbst A, Pratesi A, Fattirolli F, ... Marchionni N, Baldasseroni S
J Card Fail: 03 Aug 2021; epub ahead of print | PMID: 34358663
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Impact:
Abstract

Concurrent Assessment of the CardioMEMS HF System and HeartLogic HF Diagnostic: A Retrospective Case Series.

Chilcote JL, Summers RP, Vaz DG, Barber R, Wariar R, Guichard JL
Background
Heart failure (HF) causes high morbidity and mortality despite advances in medical therapy. Remote patient monitoring for HF allows for the optimization of medical therapy and prevention of HF hospitalizations. This study is the first to assess pulmonary artery diastolic pressures (PADP) using the CardioMEMS HF System (CMEMS) and cardiac implantable electronic device-based multisensor indexes (HeartLogic index [HLI]) using the HeartLogic HF Diagnostic (HL) in a small, retrospective cohort of patients with HF at a single center.
Methods and results
Any hospitalization, HF hospitalization, HF-related outpatient visit, and pulmonary artery pressure action were recorded in 7 patients with concurrent CMEMS and HL measurements for at least 1 year. The median time before both platforms were implanted and present in the same participant was 3.12 months. The median study period was 1.44 years per participant. Data availability for HL was significantly higher at 99.6% compared with 64.1% adherence for CMEMS (P = .016). Overall, PADP was only weakly correlated to HLI (r = 0.098), but there was a 2.87 mm Hg (P = .014) estimated increase in PADP during HLI alert periods versus nonalert periods. Similarly, the estimated odds of being above a PADP goal was 4.7 times higher (95% confidence interval 3.0-7.2, P < .001) in HLI alert vs nonalert periods.
Conclusions
Concurrent analysis of patients with CMEMS and HL showed an association between PADP and HLI, but the correlation was weak. However, there was a significant increase in PADP during HLI alert periods versus nonalert periods.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 01 Aug 2021; epub ahead of print
Chilcote JL, Summers RP, Vaz DG, Barber R, Wariar R, Guichard JL
J Card Fail: 01 Aug 2021; epub ahead of print | PMID: 34352394
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Impact:
Abstract

Nonresponse to Acute Vasodilator Challenge and Prognosis in Heart Failure With Pulmonary Hypertension.

Ghio S, Crimi G, Houston B, Montalto C, ... D\'alto M, Tedford RJ
Background
An acute vasodilator challenge is recommended in patients with heart failure and pulmonary hypertension during heart transplant evaluation. The aim of the study was to assess which hemodynamic parameters are associated with nonresponsiveness to the challenge.
Methods and results
This study is a retrospective analysis of 402 patients with heart failure with pulmonary hypertension who underwent right heart catheterization and a pulmonary vasodilator challenge. Among the 140 who fulfilled the transplant guidelines eligibility criteria for the vasodilator challenge, 38 were responders and 102 nonresponders. At multivariable analysis, a diastolic blood pressure of <70 mm Hg, pulmonary vascular resistance of >5 Woods units, and pulmonary artery compliance of <1.2 mL/mm Hg were independently associated with poor response to vasodilator challenge (all P < .001). The presence of any 2 of these 3 conditions was associated with a 90% probability of being a nonresponder. The covariate-adjusted hemodynamic predictors of death in the entire population were a low baseline systolic blood pressure (P = .0017) and a low baseline right ventricular stroke work index (P = .0395).
Conclusions
In patients with heart failure and pulmonary hypertension, low pulmonary arterial compliance, high pulmonary vascular resistance, and low diastolic blood pressure predict the nonresponsiveness to acute vasodilator challenge whilst a poor right ventricular function predicts a dismal prognosis.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jul 2021; 27:869-876
Ghio S, Crimi G, Houston B, Montalto C, ... D'alto M, Tedford RJ
J Card Fail: 30 Jul 2021; 27:869-876 | PMID: 33556547
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Impact:
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: 30 Jul 2021; 27:857-864
Saeed O, Zhang S, Patel SR, Jorde UP, ... Schwamm LH, Fonarow GC
J Card Fail: 30 Jul 2021; 27:857-864 | PMID: 33975786
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Impact:
Abstract

Rate Versus Rhythm Control in Heart Failure Patients with Post-Operative Atrial Fibrillation After Cardiac Surgery.

Yang E, Spragg D, Schulman S, Gilotra NA, ... Whitman G, Metkus TS
Background
Whether rhythm control for post-operative atrial fibrillation after cardiac surgery (POAF) is superior to rate control in patients with heart failure or systolic dysfunction (HF) is not known.
Methods
We performed a post-hoc analysis of a trial by the Cardiothoracic Surgical Trials Network, which randomized patients with POAF after cardiac surgery to rate control or rhythm control with amiodarone/cardioversion. We assessed subgroups of trial participants defined by heart failure/cardiomyopathy history or left ventricular ejection fraction (LVEF) < 50%. We conducted a stratified analysis in patients with and without HF to explore outcomes of rhythm versus rate control strategy.
Results
Of 523 subjects with POAF after cardiac surgery, 131 (25%) had HF. 49% of HF patients were randomized to rhythm control. In HF patients, rhythm control was associated with less atrial fibrillation within the first 7 days. There were no differences in rhythm at 30- and 60-day follow-up. In the HF group, there were significantly more subjects with AF < 48 hours in the rhythm control group compared to rate control group- 68.8% compared to 46.3%, P=0.009. By comparison, in the non-HF stratum, 54.4% of the rate control group had AF < 48 hours compared to 63.5% of the rhythm control group (P=0.067).), though there was no significant interaction of heart failure with cardiac rhythm at 7 days (Pinteraction 0.16).
Conclusion
Rhythm control for HF patients with POAF after cardiac surgery increases early restoration of sinus rhythm. Rate and rhythm control are both reasonable for HF patients with AF after cardiac surgery.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jul 2021; 27:915-919
Yang E, Spragg D, Schulman S, Gilotra NA, ... Whitman G, Metkus TS
J Card Fail: 30 Jul 2021; 27:915-919 | PMID: 34364670
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Impact:
Abstract

Empagliflozin in Heart Failure With Predicted Preserved Versus Reduced Ejection Fraction: Data From the EMPA-REG OUTCOME Trial.

Savarese G, Uijl A, Lund LH, Anker SD, ... Zwiener I, Butler J
Background
In the EMPA-REG OUTCOME trial, ejection fraction (EF) data were not collected. In the subpopulation with heart failure (HF), we applied a new predictive model for EF to determine the effects of empagliflozin in HF with predicted reduced (HFrEF) vs preserved (HFpEF) EF vs no HF.
Methods and results
We applied a validated EF predictive model based on patient baseline characteristics and treatments to categorize patients with HF as being likely to have HF with mid-range EF (HFmrEF)/HFrEF (EF <50%) or HFpEF (EF ≥50%). Cox regression was used to assess the effect of empagliflozin vs placebo on cardiovascular death/HF hospitalization (HHF), cardiovascular and all-cause mortality, and HHF in patients with predicted HFpEF, HFmrEF/HFrEF and no HF. Of 7001 EMPA-REG OUTCOME patients with data available for this analysis, 6314 (90%) had no history of HF. Of the 687 with history of HF, 479 (69.7%) were predicted to have HFmrEF/HFrEF and 208 (30.3%) to have HFpEF. Empagliflozin\'s treatment effect was consistent in predicted HFpEF, HFmrEF/HFrEF and no-HF for each outcome (HR [95% CI] for the primary outcome 0.60 [0.31-1.17], 0.79 [0.51-1.23], and 0.63 [0.50-0.78], respectively; P interaction = 0.62).
Conclusions
In EMPA-REG OUTCOME, one-third of the patients with HF had predicted HFpEF. The benefits of empagliflozin on HF and mortality outcomes were consistent in nonHF, predicted HFpEF and HFmrEF/HFrEF.

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

J Card Fail: 30 Jul 2021; 27:888-895
Savarese G, Uijl A, Lund LH, Anker SD, ... Zwiener I, Butler J
J Card Fail: 30 Jul 2021; 27:888-895 | PMID: 34364665
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Impact:
Abstract

Patient-centered Outcomes in HFrEF Following a Worsening Heart Failure Event: A Survey Analysis.

Dunbar SB, Tan X, Lautsch D, Yang M, ... Brady JE, Spertus JA
Background
Heart failure is a chronic disease punctuated by intermittent exacerbations that require hospitalization or intravenous diuretic therapy. The association of worsening heart failure events (WHFEs) with patient-centered outcomes in heart failure with reduced ejection fraction (HFrEF) remains unexplored.
Methods and results
Patients with HFrEF completed an online survey assessing health status, medication adherence, treatment satisfaction, treatment burden, and medication costs and affordability. Patients with and without WHFEs were compared on all study variables, with adjustment for patient characteristics using linear or logistic regression. Overall, 512 patients (52.0% WHFEs) were included. Patients with WHFEs more commonly had depression (55.3% vs 24.0%), anxiety (46.2% vs 17.9%), and insomnia (77.8% vs 44.7%; P < 0.001 for all). Patients with WHFEs had lower adjusted mean Kansas City Cardiomyopathy Questionnaire values (52.9 vs 56.0) and Satisfaction with Medications Questionnaire values (70.5 vs 72.6) and higher Treatment Burden Questionnaire scores (51.1 vs 45.1; P < 0.001). Medication-related beliefs and long-term concerns were independently associated with nonadherence in patients with WHFE (adjusted odds ratios: 4.2 and 5.2, respectively; P < 0.01 for both). Patients with WHFE incurred 50.0% higher median monthly out-of-pocket HF prescription medication costs and less often perceived HF medications to be affordable.
Conclusions
WHFE is associated with several adverse impacts on patients with HFrEF. Additional support is warranted to manage symptoms, comorbidities, and HF treatments to improve adherence and outcomes.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jul 2021; 27:877-887
Dunbar SB, Tan X, Lautsch D, Yang M, ... Brady JE, Spertus JA
J Card Fail: 30 Jul 2021; 27:877-887 | PMID: 34364664
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Abstract

Health-Related Quality of Life Is a Mediator of the Relationship Between Medication Adherence and Cardiac Event-Free Survival in Patients with Heart Failure.

Wu JR, Moser DK
Background
Health-related quality of life (HRQOL) is an important patient-reported outcome that is related to medication adherence, hospitalization and death. The nature of the relationships among medication adherence, HRQOL, and hospitalization and death is unknown. We sought to determine the relationships among medication adherence, HRQOL, and cardiac event-free survival in patients with heart failure.
Methods and results
We enrolled 218 patients with heart failure. Patients\' medication adherence was measured objectively using the Medication Event Monitoring System. HRQOL was assessed using the Minnesota Living with Heart Failure Questionnaire. Patients were followed for up to 3.5 years to collect hospitalization and mortality data. Mediation analysis was used to determine the nature of the relationships among the variables. Patients with better medication adherence had better HRQOL (P = .014). Medication adherence and HRQOL were associated with cardiac event-free survival (both P < .05). Patients with medication nonadherence were 1.86 times more likely to experience a cardiac event than those with better medication adherence (P = .038). Medication adherence was not associated with cardiac event-free survival after entering HRQOL in the model (P = .118), indicating mediation by HRQOL of the relationship between medication adherence and cardiac event-free survival.
Conclusions
HRQOL mediated the relationship between medication adherence and cardiac event-free survival. It is important to assess medication adherence and HRQOL regularly and develop interventions to improve medication adherence and HRQOL to decrease hospitalization and mortality in patients with heart failure.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jul 2021; 27:848-856
Wu JR, Moser DK
J Card Fail: 30 Jul 2021; 27:848-856 | PMID: 34364662
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Abstract

National Trends in the Use of Sacubitril/Valsartan.

Ozaki AF, Krumholz HM, Mody FV, Jackevicius CA
Background
Better understanding of recent sacubitril/valsartan prescription patterns may help identify factors that influence its use. The aim of the study was to characterize sacubitril/valsartan use and dosage patterns nationally.
Methods and results
We conducted a population-level cohort study using IQVIA Inc. National Prescription Audit™ data in the United States from August 2016 to July 2019. Over 3 years, there was a 5.6-fold increase in the number of sacubitril/valsartan prescriptions dispensed per month, totaling 3.3 million prescriptions. For the most recent year, this extrapolates to a best-case scenario of 13.8% of patients with heart failure with reduced ejection fraction using sacubitril/valsartan, representing at most one-half of those eligible for sacubitril/valsartan use. During the most recent year, 48.7% of dispensed prescriptions were for the lowest strength (24/26 mg) and only 20.6% for the target strength (97/103 mg). A greater proportion of the target strength was used in younger patients (< 65years: 24.6%; ≥ 85: 11.1%; P<0.0001). Cardiologists prescribed 59.0% of all dispensed prescriptions, and noncardiologists showed a greater increase (7.5-fold vs 4.9-fold; P<0.0001) over time.
Conclusions
Recent use of sacubitril/valsartan has increased greatly in the United States; however, a substantial proportion of eligible patients with heart failure with reduced ejection fraction did not receive treatment, and only 1 in 5 prescriptions dispensed were for the target strength. Further exploration of barriers to the use of sacubitril/valsartan and dosing uptitration and their clinical implications warrant further evaluation.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jul 2021; 27:839-847
Ozaki AF, Krumholz HM, Mody FV, Jackevicius CA
J Card Fail: 30 Jul 2021; 27:839-847 | PMID: 34364661
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Abstract

Sacubitril/Valsartan Initiation and Postdischarge Adherence Among Patients Hospitalized for Heart Failure.

Carnicelli AP, Lippmann SJ, Greene SJ, Mentz RJ, ... Fonarow GC, O\'Brien EC
Background
We investigated associations between timing of sacubitril/valsartan initiation and postdischarge adherence among patients hospitalized for heart failure with reduced ejection fraction (HFrEF). Clinical trials support initiation of sacubitril/valsartan among patients hospitalized with HFrEF. The association between timing of initiation and postdischarge adherence is unknown.
Methods and results
We analyzed patients hospitalized for HFrEF (EF of ≤40%) within the Get With The Guidelines Heart Failure registry linked with Medicare claims between October 2015 and September 2017 who were eligible for sacubitril/valsartan. Follow-up was through December 2018. Patients were grouped by timing of sacubitril/valsartan initiation. Sacubitril/valsartan adherence at 90 and 365 days after discharge was assessed by calculating proportion of days covered (PDC) using medication fills. Among 4666 patients, 108 (2.3%) were continued on sacubitril/valsartan (on sacubitril/valsartan at admission and discharge), 191 (4.1%) were initiated as inpatients, 130 (2.8%) were initiated at discharge, and 4237 (90.1%) were discharged without sacubitril/valsartan. Median (25th, 75th) proportion of days covered through 90 days among those continued, initiated as inpatients, and initiated at discharge was 0.9 (0.6-0.1), 0.3 (0.0-0.7), and 0.0 (0.0-0.7), respectively (P < .001). Patients discharged without sacubitril/valsartan had very low rates of any sacubitril/valsartan fills within 90 and 365 days of discharge (2.1% and 7.7% of surviving patients, respectively).
Conclusions
In 2015-2017 US clinical practice, more than 90% of eligible patients hospitalized for HFrEF were discharged without sacubitril/valsartan. Patients initiated as inpatients had a higher postdischarge proportion of days covered than patients initiated at discharge. Patients discharged without sacubitril/valsartan were unlikely to receive it during follow-up. These findings highlight the importance of initiating sacubitril/valsartan during hospitalization to improve the quality of care.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jul 2021; 27:826-836
Carnicelli AP, Lippmann SJ, Greene SJ, Mentz RJ, ... Fonarow GC, O'Brien EC
J Card Fail: 30 Jul 2021; 27:826-836 | PMID: 34364659
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Abstract

Dynamics of Left Ventricular Myocardial Work in Patients Hospitalized for Acute Heart Failure.

Sahiti F, Morbach C, Henneges C, Stefenelli U, ... Angermann CE, Störk S
Background
The left ventricular ejection fraction (LVEF) is the most commonly used measure describing pumping efficiency, but it is heavily dependent on loading conditions and therefore not well-suited to study pathophysiologic changes. The novel concept of echocardiography-derived myocardial work (MyW) overcomes this disadvantage as it is based on LV pressure-strain loops. We tracked the in-hospital changes of indices of MyW in patients admitted for acute heart failure (AHF) in relation to their recompensation status and explored the prognostic utility of MyW indices METHODS AND
Results:
We studied 126 patients admitted for AHF (mean 73 ± 12 years, 37% female, 40% with a reduced LVEF [<40%]), providing pairs of echocardiograms obtained both on hospital admission and prior to discharge. The following MyW indices were derived: global constructive and wasted work (GCW, GWW), global work index (GWI), and global work efficiency. In patients with HF with reduced ejection fraction with decreasing N-terminal prohormone B-natriuretic peptide levels during hospitalization, the GCW and GWI improved significantly, whereas the GWW remained unchanged. In patients with HF with preserved ejection fraction, the GCW and GWI were unchanged; however, in patients with no decrease or eventual increase in N-terminal prohormone B-natriuretic peptide, we observed an increase in GWW. In all patients with AHF, higher values of GWW were associated with a higher risk of death or rehospitalization within 6 months after discharge (per 10-point increment hazard ratio 1.035, 95% confidence interval 1.005-1.065).
Conclusions
Our results suggest differential myocardial responses to decompensation and recompensation, depending on the HF phenotype in patients presenting with AHF. The GWW predicted the 6-month prognosis in these patients, regardless of LVEF. Future studies in larger cohorts need to confirm our results and identify determinants of short-term and longer term changes in MyW.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 28 Jul 2021; epub ahead of print
Sahiti F, Morbach C, Henneges C, Stefenelli U, ... Angermann CE, Störk S
J Card Fail: 28 Jul 2021; epub ahead of print | PMID: 34332057
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Abstract

Fatigue in Persons With Heart Failure: A Systematic Literature Review and Meta-Synthesis Using the Biopsychosocial Model of Health.

Pavlovic NV, Gilotra NA, Lee CS, Ndumele C, ... Dennisonhimmelfarb C, AbshireSaylor M
Background
Fatigue is a common and distressing symptom of heart failure (HF) and has important implications for patient-reported and clinical outcomes. Despite being a common and bothersome symptom, fatigue has been understudied in HF. We sought to synthesize existing literature on fatigue in HF through a systematic literature review guided by the biopsychosocial model of health.
Methods and results
A systematic search of the literature was performed on March 18, 2020, using Pubmed, Embase, and CINAHL. Full-text, primary research articles, written in English, in which fatigue was a primary symptom of interest in adults with a diagnosis of HF, were included. The search yielded 1138 articles; 33 articles that met inclusion criteria were selected for extraction and synthesis. Biological and psychological factors associated with fatigue were New York Heart Association functional class, hemoglobin level, history of stroke, and depression. However, there are limited HF-specific factors linked to fatigue. Social factors related to fatigue included social roles, relationship strain, and loneliness and isolation. Few nonpharmacologic interventions have been tested by show some promise for alleviating fatigue in HF. Studies show conflicting evidence related to the prognostic implications of fatigue.
Conclusions
Important biological correlates of fatigue were identified; however, psychological and social variables were limited to qualitative description. There is need for expanded models to better understand the complex physiologic nature of fatigue in HF. Additionally, more research is needed to (1) define the relationships between fatigue and both psychological and social factors, (2) better describe the prognostic implications of fatigue, and (3) develop more therapeutic approaches to alleviate fatigue with the goal of improving overall quality of life.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 27 Jul 2021; epub ahead of print
Pavlovic NV, Gilotra NA, Lee CS, Ndumele C, ... Dennisonhimmelfarb C, AbshireSaylor M
J Card Fail: 27 Jul 2021; epub ahead of print | PMID: 34329719
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This program is still in alpha version.