Journal: J Card Fail

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Abstract

Associations of angiopoietins with heart failure incidence and severity.

Peplinski BS, Houston BA, Bluemke DA, Kawut SM, ... Tedford RJ, Leary PJ
Background
Angiopoietin-1 and 2 (Ang1, Ang2) are important mediators of angiogenesis. Angiopoietin levels are perturbed in cardiovascular disease, but it is unclear whether angiopoietin signaling is causative, an adaptive response, or merely epiphenomenon of disease activity.
Methods and results
In a cohort free of cardiovascular disease at baseline (MESA), relationships between angiopoietins, cardiac morphology, and subsequent incidence of heart failure or cardiovascular death were evaluated. In cohorts with pulmonary arterial hypertension (PAH) or left heart disease (LHD), associations between angiopoietins, invasive hemodynamics, and adverse clinical outcomes were evaluated. In MESA, Ang2 was associated with a higher incidence of heart failure or cardiovascular death (HR 1.21 per standard deviation, P<0.001). Ang2 was associated with increased right atrial pressure (PAH cohort) and increased wedge pressure and right atrial pressure (LHD cohort). Elevated Ang2 was associated with mortality in the PAH cohort.
Conclusion
Ang2 was associated with incident heart failure or death among adults without cardiovascular disease at baseline and with disease severity in individuals with existing heart failure. Our findings that Ang2 is elevated prior to disease onset and that elevations reflect disease severity, suggest Ang2 may contribute to heart failure pathogenesis.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 15 Apr 2021; epub ahead of print
Peplinski BS, Houston BA, Bluemke DA, Kawut SM, ... Tedford RJ, Leary PJ
J Card Fail: 15 Apr 2021; epub ahead of print | PMID: 33872759
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Abstract

Cardiac thyrotropin-releasing hormone (TRH) inhibition improves ventricular function and reduces hypertrophy and fibrosis after myocardial infarction in rats.

Schuman ML, Diaz LSP, Aisicovich M, Ingallina F, ... Landa MS, García SI
Background
Cardiac thyrotropin-releasing hormone (TRH) is a tripeptide with still unknown functions. We demonstrated that the left ventricle (LV) TRH system is hyperactivated in spontaneously hypertensive rats and its inhibition prevented cardiac hypertrophy and fibrosis. Therefore, we evaluated whether in vivo cardiac TRH inhibition could improve myocardial function and attenuate ventricular remodeling in a rat model of myocardial infarction (MI).
Methods and results
In Wistar rats, MI was induced by a permanent left anterior descending coronary artery ligation. A coronary injection of a specific siRNA against TRH was simultaneously applied. The control group received a scrambled siRNA. Cardiac remodeling variables were evaluated one week later. In MI rats, TRH inhibition decreased LV end-diastolic (1.049±0.102 vs. 1.339±0.102 ml, p<0.05), and end-systolic volumes (0.282±0.043 vs. 0.515±0.037 ml, p<0.001), and increased LV ejection fraction (71.89±2.80 vs. 65.69±2.85 %, p<0.05). Although both MI groups presented similar infarct size, siRNA-the TRH treatment attenuated the cardiac hypertrophy index and myocardial interstitial collagen deposition in the peri-infarct myocardium. These effects were accompanied by attenuation in the rise of TGFβ, collagen I, and III and also the fetal genes (ANP, BNP, and βMHC) expression in the peri-infarct region. Besides, the expression of Hif1α and VEGF significantly increased compared to all groups.
Conclusions
Cardiac TRH inhibition improves LV systolic function and attenuates ventricular remodeling after MI. These novel findings support the idea that TRH inhibition may serve as a new therapeutic strategy against the progression of heart failure.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 14 Apr 2021; epub ahead of print
Schuman ML, Diaz LSP, Aisicovich M, Ingallina F, ... Landa MS, García SI
J Card Fail: 14 Apr 2021; epub ahead of print | PMID: 33865967
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Abstract

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

Mitchell JE, Chesler R, Zhang S, Matsouaka RA, ... Chang NL, Fonarow GC
Background
There is a paucity of information on patients hospitalized with heart failure [HF] who leave against medical advice [AMA].
Objectives
We sought to identify patient and hospital characteristics and outcomes of patients with HF who left AMA compared to those conventionally discharged to home [CDH].
Methods
Using the Get With The Guidelines-Heart Failure registry, data were analyzed from January 2010 to June 2019. In addition, outcomes were examined from a subset of hospitalizations with Medicare-linked claims between January 2010 and November 2015. Fully eligible population included 561,823 patients; the Medicare-linked subset included 74,502 patients.
Results
In total, 8747 patients (1.56%) left AMA. The proportion of patients leaving AMA increased from 1.1 to 2.1% over the years of study. Patients leaving a HF hospitalization AMA, compared to patients CDH, were more likely younger, minorities, Medicaid covered or uninsured. The Medicare-linked subset of patients who left AMA had substantially higher 30-day and 12-month readmission rates and higher mortality at each assessment point over 12 months compared to patients who were CDH. After risk adjustments, the hazard ratio of mortality in the Medicare-linked subset AMA group compared to the CDH group was 1.25 (95% CI 1.03, 1.51), p=0.005.
Conclusions
One in 64 hospitalized patients with HF left AMA. An AMA discharge status was associated with higher risk for adverse 30 day and 12-month outcomes compared to being conventionally discharged home. Strategies that identify patients at risk of leaving AMA and policies to direct interventional strategies are warranted.
Condensed abstract
We investigated patient characteristics, hospital factors and clinical outcomes associated with patients leaving a HF hospitalization against medical advice compared with being conventionally discharged to home. Using GWTG, a national registry, we found that patients who left AMA were more likely to be younger, minorities, Medicaid insured or uninsured; they had higher readmission and post-discharge mortality rates. Hospital characteristics associated with higher AMA discharges were for-profit structure and Western U.S.
Location
As HF prevalence increases, attention and interventions that support patients who chose to leave AMA and the hospitals from which they leave are needed.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 13 Apr 2021; epub ahead of print
Mitchell JE, Chesler R, Zhang S, Matsouaka RA, ... Chang NL, Fonarow GC
J Card Fail: 13 Apr 2021; epub ahead of print | PMID: 33864931
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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 re-distribution of blood from the unstressed venous reservoir to the hemodynamically active stressed compartment is thought to contribute to congestion in cardiogenic shock. We employed a novel computational method to estimate stressed blood volume in cardiogenic shock and assess its relationship with clinical outcomes.
Methods
Hemodynamic parameters including estimated stressed blood volume (eSBV) were compared among patients from the Cardiogenic Shock Working Group (CSWG) registry with a complete set of hemodynamic data. eSBV was compared across shock etiologies (AMI vs HF-CS), SCAI stage, and between survivors and non-survivors.
Results
Among 528 CS patients analyzed, mean eSBV was 2423 mL/70 kg and increased with increasing SCAI stage (B, 2029; C, 2305; D, 2496; E, 2707 mL/70 kg, p<0.001). eSBV was significantly higher among HF-CS patients who died compared with survivors (2733 vs 2357 mL/70 kg, p<0.001), while no significant difference was observed between outcome groups in AMI-CS (2501 vs 2384 ml/70kg, p=0.19)
Conclusions:
: eSBV is a novel integrated index of congestion which correlates with shock severity. eSBV was higher in patients with HF-CS who died while no difference was observed in AMI-CS, suggesting that congestion may play a more significant role in the deterioration of patients with HF-CS.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 12 Apr 2021; epub ahead of print
Whitehead EH, Thayer KL, Sunagawa K, Hernandez-Montfort J, ... Kapur NK, Burkhoff D
J Card Fail: 12 Apr 2021; epub ahead of print | PMID: 33862252
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Abstract

Changes of Right Ventricular Function after Transcatheter Aortic Valve Replacement and Association with Outcome.

Poch F, Thalmann R, Olbrich I, Fellner C, ... Kupatt C, Ledwoch J
Objective
Baseline right ventricular (RV) dysfunction represents a predictor for poor outcome in patients undergoing transcatheter aortic valve replacement (TAVR). However, RV function may improve after TAVR, which could have important implications on outcome. The aim of the present study was to assess changes in RV function after TAVR and its prognostic value regarding clinical outcome.
Methods
Patients undergoing TAVR at our institution were consecutively enrolled and categorized into 4 groups according to changes in RV function during echocardiographic follow-up at 6 months.
Results
A total of 188 patients were included. Of those showing normal function at baseline, in 87% (130/149) of patients RV function was preserved at follow-up (group 1), whereas 13% (19/149) of patients developed new RV dysfunction (group 2). Of those with RV dysfunction at baseline (39 patients), RV function normalized in 46% (18/39) (group 3) and remained impaired in 54% (21/39) (group 4). Kaplan-Meier estimated survival at 3 years was highest in patients in group 1 (83%), intermediate in group 2 (65%) and 3 (69%), whereas group 4 had the worst survival (37%; p<0.001). Furthermore, new or persistent RV dysfunction was identified to be independently associated with mortality during follow-up (HR 2.55 [1.03 - 6.47]; p=0.004).
Conclusion
Patients with preserved RV function have high 3-year survival. Normalization of RV function showed improved survival compared to patients with persistent RV dysfunction, who had a dismal prognosis despite TAVR.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 07 Apr 2021; epub ahead of print
Poch F, Thalmann R, Olbrich I, Fellner C, ... Kupatt C, Ledwoch J
J Card Fail: 07 Apr 2021; epub ahead of print | PMID: 33839289
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Abstract

Iron deficiency is associated with impaired biventricular reserve and reduced exercise capacity in patients with unexplained dyspnea.

Martens P, Claessen G, Van De Bruaene A, Verbrugge FH, ... Dendale P, Verwerft J
Background
Iron deficiency (ID) is frequent and associated with diminished exercise capacity in heart failure (HF), but its contribution to unexplained dyspnea without a HF diagnosis at rest remains unclear.
Methods
Consecutive patients with unexplained dyspnea and normal echocardiography and pulmonary function tests at rest underwent prospective standardized cardiopulmonary exercise testing with echocardiography (CPETecho) in a tertiary care dyspnea clinic. ID was defined as ferritin <300µg/l and transferrin saturation (TSAT)<20% and its impact on peak oxygen uptake (peakVO2), biventricular response to exercise, and peripheral oxygen extraction was assessed.
Results
Of 272 CPETecho patients, 63 (23%) had ID. For a similar respiratory exchange ratio, patients with ID had lower peakVO2 (14.6±7.6 vs 17.8±8.8ml/kg/min; p=0.009) and maximal workload (89±50 vs 108±56 watt p=0.047), even after adjustment for the presence of anemia. At rest, patients with ID had a similar left ventricular and right ventricular (RV) contractile function. During exercise, patients with ID had lower cardiac output reserve (p<0.05) and depressed RV function by tricuspid s\' (p=0.004), tricuspid annular plane systolic excursion (TAPSE; p=0.034) and RV end-systolic pressure-area ratio (RVESPAR; p=0.038), with more RV-pulmonary artery uncoupling measured by TAPSE/systolic pulmonary arterial pressure ratio (p=0.023). RVESPAR change from rest to peak exercise, as a load-insensitive metric of RV contractility, was lower in patients with ID (2.09±0.72 vs. 2.58±1.14 mmHg/cm2; p<0.001). ID was associated with impaired peripheral oxygen extraction (peakVO2/peak cardiac output; p=0.036). CPETecho resulted in a diagnosis of HF with preserved ejection fraction in 71 patients (26%) based on an exercise E/e\' ratio above 14, with equal distribution in patients with (28.6%) or without ID (25.4%, p=0.611). None of the aforementioned findings were influenced in a sensitivity analysis adjusted for a final diagnosis of HFpEF as etiology for the unexplained dyspnea.
Conclusion
In patients with unexplained dyspnea without clear HF at rest, ID is common and associated with reduced exercise capacity, diminished biventricular contractile reserve and reduced peripheral oxygen extraction.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 06 Apr 2021; epub ahead of print
Martens P, Claessen G, Van De Bruaene A, Verbrugge FH, ... Dendale P, Verwerft J
J Card Fail: 06 Apr 2021; epub ahead of print | PMID: 33838251
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Abstract

Validity of Hemodynamic Monitoring Using Inert Gas Rebreathing Method in Patients With Chronic Heart Failure and Those Implanted With a Left Ventricular Assist Device.

Okwose NC, Bouzas-Cruz N, Fernandez OG, Koshy A, ... Macgowan GA, Jakovljevic DG
Objective
The present study assessed agreement between resting cardiac output estimated by inert gas rebreathing (IGR) and thermodilution methods in patients with heart failure and those implanted with a left ventricular assist device (LVAD).
Methods and results
Hemodynamic measurements were obtained in 42 patients, 22 with chronic heart failure and 20 with implanted continuous flow LVAD (34 males, aged 50 ± 11 years). Measurements were performed at rest using thermodilution and IGR methods. Cardiac output derived by thermodilution and IGR were not significantly different in LVAD (4.4 ± 0.9 L/min vs 4.7 ± 0.8 L/min, P = .27) or patients with heart failure (4.4 ± 1.4 L/min vs 4.5 ± 1.3 L/min, P = .75). There was a strong relationship between thermodilution and IGR cardiac index (r = 0.81, P = .001) and stroke volume index (r = 0.75, P = .001). Bland-Altman analysis showed acceptable limits of agreement for cardiac index derived by thermodilution and IGR, namely, the mean difference (lower and upper limits of agreement) for patients with heart failure -0.002 L/min/m2 (-0.65 to 0.66 L/min/m2), and -0.14 L/min/m2 (-0.78 to 0.49 L/min/m2) for patients with LVAD.
Conclusions
IGR is a valid method for estimating cardiac output and should be used in clinical practice to complement the evaluation and management of chronic heart failure and patients with an LVAD.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Mar 2021; 27:414-418
Okwose NC, Bouzas-Cruz N, Fernandez OG, Koshy A, ... Macgowan GA, Jakovljevic DG
J Card Fail: 30 Mar 2021; 27:414-418 | PMID: 33035686
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Abstract

Ventilation Dispersion Index as an Objective Evaluation Tool of Exercise Oscillatory Ventilation in Patients With Heart Failure.

Corte RC, De Sá J, Carlos R, Felismino AS, ... Pereira E, Bruno S
Background
Exercise oscillatory ventilation (EOV) is related to worse prognosis in patients with heart failure (HF). However, its determination is subjective and there is no standard measure to identify it. The aim of the study was to evaluate and characterize the EOV of patients with HF using the ventilation dispersion index (VDI).
Methods and results
Patients underwent cardiopulmonary exercise testing (CPX), EOV was assessed by 2 reviewers and the VDI was calculated. The receiver operator curve analysis was used to assess the ability of the VDI to predict EOV. Pearson\'s correlation test was performed to determine the relationship between VDI and CPX variables. Forty-three patients with HF underwent CPX and were divided into 2 groups: with a VDI of less than 0.601 and a VDI of 0.601 or greater. An area under the curve of 0.759 was observed in the receiver operator curve analysis between VDI and EOV (P = .008). The VDI showed a significant correlation with the ventilatory CPX variables. According to the cut-off point obtained on the receiver operator curve, patients with a VDI of 0.601 or greater had lower left ventricular ejection fraction and higher values of resting minute ventilation and peak minute ventilation.
Conclusions
The VDI proved to be a good predictor of EOV in patients with HF.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Mar 2021; 27:419-426
Corte RC, De Sá J, Carlos R, Felismino AS, ... Pereira E, Bruno S
J Card Fail: 30 Mar 2021; 27:419-426 | PMID: 33038533
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Abstract

Soluble ST2 and Diuretic Efficiency in Acute Heart Failure and Concomitant Renal Dysfunction.

Espriella R, Bayés-Genis A, Revuelta-LóPEZ E, Miñana G, ... Núñez J, IMPROVE-HF Investigators
Background
Identifying patients at risk of poor diuretic response in acute heart failure (AHF) is critical to make prompt adjustments in therapy. The objective of this study was to investigate whether the circulating levels of soluble ST2 predict the cumulative diuretic efficiency (DE) at 24 and 72 hours in patients with AHF and concomitant renal dysfunction.
Methods and results
This is a post hoc analysis of the IMPROVE-HF trial, in which we enrolled 160 patients with AHF and renal dysfunction (estimated glomerular filtrate rate of <60 mL/min/1.73 m2). DE was calculated as the net fluid output produced per 40 mg of furosemide equivalents. The association between sST2 and DE was evaluated by using multivariate linear regression analysis. The median cumulative DE at 24 and 72 hour was 747 mL (interquartile range 490-1167 mL) and 1844 mL (interquartile range 1142-2625 mL), respectively. The median sST2 and mean estimated glomerular filtrate rate were 72 ng/mL (interquartile range 47-117 ng/mL), and 34.0 ± 8.5 mL/min/1.73 m2, respectively. In a multivariable setting, higher sST2 were significant and nonlinearly related to lower DE both at 24 and 72 hours (P = .002 and P = .019, respectively).
Conclusions
In patients with AHF and renal dysfunction at presentation, circulating levels of sST2 were independently and negatively associated with a poor diuretic response, both at 24 and 72 hours.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Mar 2021; 27:427-434
Espriella R, Bayés-Genis A, Revuelta-LóPEZ E, Miñana G, ... Núñez J, IMPROVE-HF Investigators
J Card Fail: 30 Mar 2021; 27:427-434 | PMID: 33038531
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Abstract

Association of Midlife Cardiovascular Risk Factors With the Risk of Heart Failure Subtypes Later in Life.

Cohen LP, Vittinghoff E, Pletcher MJ, Allen NB, ... Moran AE, Zhang Y
Background
Independent associations between cardiovascular risk factor exposures during midlife and later life development of heart failure (HF) with preserved ejection fraction (HFpEF) versus reduced EF (HFrEF) have not been previously studied.
Methods
We pooled data from 4 US cohort studies (Atherosclerosis Risk in Communities, Cardiovascular Health, Health , Aging and Body Composition, and Multi-Ethnic Study of Atherosclerosis) and imputed annual risk factor trajectories for body mass index, systolic and diastolic blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol, and glucose starting from age 40 years. Time-weighted average exposures to each risk factor during midlife and later life were calculated and analyzed for associations with the development of HFpEF or HFrEF.
Results
A total of 23,861 participants were included (mean age at first in-person visit, 61.8 ±1 0.2 years; 56.6% female). During a median follow-up of 12 years, there were 3666 incident HF events, of which 51% had EF measured, including 934 with HFpEF and 739 with HFrEF. A high midlife systolic blood pressure and low midlife high-density lipoprotein cholesterol were associated with HFrEF, and a high midlife body mass index, systolic blood pressure, pulse pressure, and glucose were associated with HFpEF. After adjusting for later life exposures, only midlife pulse pressure remained independently associated with HFpEF.
Conclusions
Midlife exposure to cardiovascular risk factors are differentially associated with HFrEF and HFpEF later in life. Having a higher pulse pressure during midlife is associated with a greater risk for HFpEF but not HFrEF, independent of later life exposures.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Mar 2021; 27:435-444
Cohen LP, Vittinghoff E, Pletcher MJ, Allen NB, ... Moran AE, Zhang Y
J Card Fail: 30 Mar 2021; 27:435-444 | PMID: 33238139
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Abstract

Diuresis-Related Weight Loss Reflects Interstitial Compartment Decongestion with Minimal Impact on Intravascular Volume Expansion or Outcomes in Post-Acute Heart Failure: Metrics of Decongestion and Volume Status.

Miller WL, Lobo R, Grill DE, Mullan BP
Background
Findings from heart failure (HF) studies linking diuresis-related weight loss to clinical decongestion and outcomes are mixed. Differential responses of interstitial and intravascular volume compartments to diuretic therapy and heterogeneity in volume profiles may confound the clinical interpretation of weight loss in patients with HF.
Methods and results
Data were prospectively collected in hospitalized patients requiring diuresis. Plasma volume (PV) was measured using I-131-labelled albumin indicator-dilution methodology. The cohort was stratified by tertiles of weight loss and analyzed for interstitial fluid loss relative to changes in PV and HF-related morality or first rehospitalization. Among 92 patients, the admission PV was expanded +42% (4.7 ± 1.2 L) above normal with significant variability (14% normal PV, 18% mild-moderate expansion, and 68% with large PV expansion [>+25% above normal]). With diuresis there were proportional decreases in interstitial volume (-6.5 ± 4.4%) and PV (-7.5 ± 11%); however, absolute decreases in the PV (-254 mL, interquartile range -11 to -583 mL) were less than 10% of interstitial volume loss (-5040 mL, interquartile range -2800 to -7989 mL); greater interstitial fluid loss did not translate into better outcomes (log-rank P = .430).
Conclusions
Diuresis-related decreases in weight reflect fluid loss from the interstitial compartment with only minor changes in the PV and without an impact on outcomes. Further, the degree of PV expansion at hospital admission does not drive the magnitude of the diuresis response, even with a wide spectrum of body weights; interstitial fluid overload is preferentially targeted and PV relatively preserved. Therefore, greater interstitial fluid loss reflects clinical decongestion, but not better outcomes, and a limited association with intravascular volume profiles potentially confounding weight loss as a prognostic metric in HF.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Mar 2021; 27:445-452
Miller WL, Lobo R, Grill DE, Mullan BP
J Card Fail: 30 Mar 2021; 27:445-452 | PMID: 33347996
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Abstract

Exercise Tolerance in Patients Treated With a Durable Left Ventricular Assist Device: Importance of Myocardial Recovery.

Dridi NP, Vishram-Nielsen JKK, Gustafsson F
The number of patients supported with left ventricular assist devices (LVADs) is growing and support times are increasing. This has led to a greater focus on functional capacity of these patients. LVADs greatly improve heart failure symptoms, but surprisingly, improvement in peak oxygen uptake (pVO2) is small and remains decreased at approximately 50% of normal values. Inadequate increase in cardiac output during exercise is the main responsible factor for the low pVO2 in LVAD recipients. Some patients experience LV recovery during mechanical unloading and these patients have a higher pVO2. Here we review the various components determining exercise cardiac output in LVAD recipients and discuss the potential impact of cardiac recovery on these components. LV recovery may affect several components, leading to improved hemodynamics during exercise and, in turn, physical capacity in patients with advanced heart failure undergoing LVAD implantation.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Mar 2021; 27:486-493
Dridi NP, Vishram-Nielsen JKK, Gustafsson F
J Card Fail: 30 Mar 2021; 27:486-493 | PMID: 33347995
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Abstract

Delirium Among Hospitalized Older Adults With Acute Heart Failure Exacerbation.

Kwak MJ, Avritscher E, Holmes HM, Jantea R, ... Balan P, Dhoble A
Background
Delirium among older adults hospitalized with acute heart failure is associated with increased mortality. However, studies concomitantly assessing the association of delirium with both clinical and economic outcomes in this population, such as mortality, hospital cost, or length of stay, are lacking.
Methods and results
We conducted a retrospective observational study using National Inpatient Sample data from 2011 to 2014. Using multivariable logistic regression, we assessed the association of delirium with in-hospital mortality, then estimated the incremental hospital cost and excessive length of stay adjusting for demographic and clinical factors using multivariable generalized linear regression. The association of other medical complications on clinical and economic outcomes was also assessed. A total of 568,565 (weighted N = 2,826,131) hospitalizations of patients 65 years or older with acute heart failure from 2011 to 2014 were included in the final analysis. The reported prevalence of delirium was 4.53%. After multivariable adjustment, delirium was associated with a 2.35-fold increase in the odds of in-hospital mortality (95% confidence interval [CI] 2.23-2.47), which was lower than the odds ratio for sepsis/septicemia (5.36; 95% CI, 5.02-5.72) or respiratory failure (4.53; 95% CI, 4.38-4.69), but similar to that for acute kidney injury (2.39; 95% CI, 2.31-2.48) and higher than for non-ST elevation myocardial infarct (1.57; 95% CI, 1.46-1.68). Delirium increased the total hospital cost by $4,262 (95% CI, $4,002-4,521) and the length of stay by 1.73 days (95% CI, 1.68-1.78), which was slightly lower than, but similar to, acute kidney injury ($4,771; 95% CI, $4,644-4,897) and 1.82 days (95% CI, 1.79-1.84), and higher than non-ST elevation myocardial infarct ($1,907; 95% CI, $1,629-2,185) and 0.31 days (95% CI, 0.25-0.37).
Conclusions
Delirium was associated with increased in-hospital mortality, total hospital cost, and length of stay, and the magnitude of the effect was similar to that for acute kidney injury. Enhanced efforts to prevent delirium are needed to decrease its adverse impact on clinical and economic outcomes for hospitalized older adults with acute heart failure.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Mar 2021; 27:453-459
Kwak MJ, Avritscher E, Holmes HM, Jantea R, ... Balan P, Dhoble A
J Card Fail: 30 Mar 2021; 27:453-459 | PMID: 33347994
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Abstract

Social Determinants of Health and Rates of Implantation for Patients Considering Destination Therapy Left Ventricular Assist Device.

Flint K, Chaussee EL, Henderson K, Breathett K, ... Matlock DD, Allen LA
Background
A left ventricular assist device (LVAD) is a treatment option available to select patients with advanced heart failure. However, there are important social determinants of health that can play a role in determining patients\' outcomes after device placement.
Methods and results
We leveraged the DECIDE-LVAD Trial to assess social determinants of health-relationship status, household income, race/ethnicity, educational attainment, and health insurance-at the time of evaluation, and their association with rate of LVAD placement in the subsequent year. About a quarter of patients were unpartnered (i.e., single/divorced/widowed/separated; n = 55 [26%]). A similar proportion had a household income of less than $20,000 per year (n = 50 [24%]). Few patients were other race (n = 39 [18%]), had less than a high school education (n = 14 [6.6%]), or had Medicaid as their primary payor (n = 17 [8.4%]). LVAD implantation was significantly lower among patients who were unpartnered compared with patients who were married or partnered. LVAD implantation was not associated with income, race, educational attainment or insurance status.
Conclusions
Our data from diverse LVAD centers at U.S. private and academic hospitals found that, among a broad sample of patients being evaluated for LVAD, married or partnered status was favorably associated with LVAD implantation, but other social determinants of health were not. Future research and policy changes should consider novel interventions for improving access to LVAD implantation for patients with inadequate social support.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Mar 2021; 27:497-500
Flint K, Chaussee EL, Henderson K, Breathett K, ... Matlock DD, Allen LA
J Card Fail: 30 Mar 2021; 27:497-500 | PMID: 33346077
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Abstract

Influence of Donor Transmitted and Rapidly Progressive Coronary Vascular Disease on Long-Term Outcomes After Heart Transplantation: A Contemporary Intravascular Ultrasound Analysis.

Sperry BW, Qarajeh R, Omer MA, Brandt H, ... Kao AC, Austin BA
Background
Donor-transmitted atherosclerosis (DTA) and rapidly progressive cardiac allograft vasculopathy (CAV) at 1 year are intravascular ultrasound (IVUS)-derived measures shown to predict adverse cardiovascular outcomes in the setting of early generation immunosuppressive agents. Given the paucity of data on the prognostic value of IVUS-derived measurements in the current era, we sought to explore their association with adverse outcomes after heart transplantation.
Methods and results
This is a retrospective cohort analysis of patients who underwent heart transplantation at our center between January 2009 and June 2016 with baseline and 1-year IVUS. Five IVUS sections were prospectively analyzed for intimal thickness and lumen area. DTA was defined as maximum intimal thickness of 0.5 mm or greater at baseline, and rapidly progressive CAV as an increase in maximum intimal thickness by 0.5 mm or more at 1 year. Our primary analysis assessed the relationship of IVUS and other clinical data on a composite outcome: coronary intervention, CAV stage 2 or 3 (defined by the International Society for Heart and Lung Transplantation 2010 nomenclature), or cardiovascular death. Among 249 patients (mean age 51.0 ± 12.2 years and 74.3% male) included in the analysis, DTA was detected in 118 patients (51.4%). Over a median follow-up of 6.1 years (interquartile range 4.2-8.0 years), 45 patients met the primary end point (23 percutaneous coronary intervention, 11 CAV 2 or 3, and 11 cardiovascular deaths as first event). DTA and rapidly progressive CAV were not associated with the primary end point, all-cause mortality, or retransplantation. In an additional analysis including post-transplant events, incident rejection was strongly associated with poor outcomes, although cytomegalovirus infection was not.
Conclusions
In this contemporary cohort, IVUS-derived DTA and rapidly progressive CAV were not associated with medium- to long-term adverse events after heart transplantation.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Mar 2021; 27:464-472
Sperry BW, Qarajeh R, Omer MA, Brandt H, ... Kao AC, Austin BA
J Card Fail: 30 Mar 2021; 27:464-472 | PMID: 33358960
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Abstract

Limited Balloon Atrial Septostomy for Left Ventricular Unloading in Peripheral Extracorporeal Membrane Oxygenation.

Amancherla K, Menachem JN, Shah AS, Lindenfeld J, O\'leary J
Background
This study describes the authors\' experience with a limited balloon atrial septostomy technique, using a median balloon size of 15 mm, as a left ventricular (LV) unloading strategy in venoarterial extracorporeal membrane oxygenation (VA-ECMO). There has been increasing use of VA-ECMO in cardiogenic shock. Although LV unloading strategies have been suggested to improve outcomes, it is unclear which strategy is optimal.
Methods and results
We performed a retrospective study of patients who underwent a limited balloon atrial septostomy for LV unloading in peripheral VA-ECMO at a single center. The goal of this study was to define the procedural outcomes and clinical characteristics of these patients. Of the 12 patients identified, none had complications related to the procedure. There was a significant decrease in the mean left atrial pressure and the majority of patients had radiologic improvement in pulmonary vascular congestion. Of the 12 patients, 58.3% survived to discharge.
Conclusions
Limited BAS is an elegant and safe method for unloading the LV in peripheral VA-ECMO.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Mar 2021; 27:501-504
Amancherla K, Menachem JN, Shah AS, Lindenfeld J, O'leary J
J Card Fail: 30 Mar 2021; 27:501-504 | PMID: 33358956
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Impact:
Abstract

Phosphodiesterase-5 Inhibitors and Outcomes During Left Ventricular Assist Device Support: A Systematic Review and Meta-Analysis.

Kittipibul V, Blumer V, Angsubhakorn N, Hernandez GA, ... Tedford RJ, Agarwal R
Background
Phosphodiesterase-5 inhibitors (PDE5i) have been used to treat pulmonary hypertension and right ventricular failure in patients with left ventricular assist devices (LVAD). The effects of PDE5i on post-LVAD outcomes including hemocompatibility-related adverse events are not well-established. This systematic review and meta-analysis aims to evaluate the effects of PDE5i on post-LVAD outcomes.
Methods and results
A comprehensive literature search was conducted using Pubmed and Embase databases from inception through November 25, 2020, to compare post-LVAD outcomes in patients with or without PDE5i use. Pooled odds ratio (OR) with 95% confidence intervals (CI) and I2 statistic were calculated. Thirteen observational studies were included in this analysis. The use of PDE5i was not significantly associated with lower postoperative right ventricular failure (OR 0.38, 95% CI 0.02-5.96, P = .41). There was no significant association between PDE5i and gastrointestinal bleeding (OR 1.23, 95% CI 0.76-1.98, P = .2), overall stroke (OR 0.60, 95% CI 0.21-1.68, P = .17), ischemic stroke (OR 0.61, 95% CI 0.09-4.07, P = .38), or pump thrombosis (OR 0.71, 95% CI 0.14-3.54, P = .46).
Conclusions
Our meta-analysis showed no significant association between PDE5i and post-LVAD right ventricular failure. Despite the antiplatelet effects of PDE5i, there was no significant association between PDE5i and gastrointestinal bleeding, overall stroke, ischemic stroke, or pump thrombosis. Randomized controlled studies are warranted to evaluate the net benefits or harms of PDE5i in the LVAD population.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Mar 2021; 27:477-485
Kittipibul V, Blumer V, Angsubhakorn N, Hernandez GA, ... Tedford RJ, Agarwal R
J Card Fail: 30 Mar 2021; 27:477-485 | PMID: 33385522
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Impact:
Abstract

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

Sammour Y, DeZorzi C, Austin BA, Borkon AM, ... Kao AC, Sperry BW
Background
Statins are recommended in heart transplant patients, but are sometimes poorly tolerated. Alternative agents are often considered including PCSK9 inhibitors (PCSK9i). We sought to investigate the use of PCSK9i after heart transplant.
Methods
We identified patients who received a heart transplant from 1999 - 2019 and were started on PCSK9i at our institution. Clinical, laboratory, and coronary angiography with intravascular ultrasound results were compared.
Results
Among 65 patients initiated on PCSK9i (48 for statin intolerance and 17 for refractory hyperlipidemia), the median time from transplant was 5.5 (2.8-9.9) years with median PCSK9 treatment duration of 1.6 (0.8-3.2) years and 80% still on treatment. Evolocumab was used in 73.8%, Alirocumab in 12.3%, and both in 13.8% due to insurance coverage. All patients required prior authorization, and initial denial occurred in 18.5%, while 32.3% had denials in subsequent years. Median LDL-C decreased from 130 (102-148) mg/dL to 55 (35-74) mg/dL after starting PCSK9i (p<0.001), with 72% of patients achieving LDL-C <70 mg/dL after treatment. There were also significant reductions of total-C, non-HDL-C, total/HDL-C ratio and triglycerides, with a modest increase in HDL-C. These changes were durable at latest follow-up. In 33 patients with serial coronary angiography and intravascular ultrasound, PCSK9i were associated with stabilization of coronary plaque thickness and lumen area.
Conclusion
Among heart transplant recipients, PCSK9i are effective in lowering cholesterol levels and stabilizing coronary intimal hyperplasia with minimal side effects. Despite favorable effects, access and affordability remain a challenge.

Copyright © 2021. Published by Elsevier Inc.

J Card Fail: 18 Mar 2021; epub ahead of print
Sammour Y, DeZorzi C, Austin BA, Borkon AM, ... Kao AC, Sperry BW
J Card Fail: 18 Mar 2021; epub ahead of print | PMID: 33753241
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Impact:
Abstract

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

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

Published by Elsevier Inc.

J Card Fail: 13 Mar 2021; epub ahead of print
Kaufman BG, Granger BB, Sun JL, Sanders G, ... O'Connor C, Mentz RJ
J Card Fail: 13 Mar 2021; epub ahead of print | PMID: 33731305
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Impact:
Abstract

Universal Definition and Classification of Heart Failure: A Report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure.

Bozkurt B, Coats AJ, Tsutsui H, Abdelhamid M, ... Zhang J, Zieroth S
In this document, we propose a universal definition of heart failure (HF) as the following: HF is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and or objective evidence of pulmonary or systemic congestion. We propose revised stages of HF as follows. At-risk for HF (Stage A), for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease. Pre-HF (stage B), for patients without current or prior symptoms or signs of HF, but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels. HF (Stage C), for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality. Advanced HF (Stage D), for patients with severe symptoms and/or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT), refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care. Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). The classification includes HF with reduced EF (HFrEF): HF with an LVEF of ≤40%; HF with mildly reduced EF (HFmrEF): HF with an LVEF of 41% to 49%; HF with preserved EF (HFpEF): HF with an LVEF of ≥50%; and HF with improved EF (HFimpEF): HF with a baseline LVEF of ≤40%, a ≥10-point increase from baseline LVEF, and a second measurement of LVEF of >40%.

Published by Elsevier Inc.

J Card Fail: 28 Feb 2021; epub ahead of print
Bozkurt B, Coats AJ, Tsutsui H, Abdelhamid M, ... Zhang J, Zieroth S
J Card Fail: 28 Feb 2021; epub ahead of print | PMID: 33663906
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Impact:
Abstract

Patient stratification for risk of readmission due to heart failure by using nationwide administrative data.

Constantinou P, Pelletier-Fleury N, Olié V, Gastaldi-Ménager C, JuillÈre Y, Tuppin P
Background
Identifying patients with heart failure (HF) who are most at risk of readmission permits targeting adapted interventions. The use of administrative data enables regulators to support the implementation of such interventions.
Methods and results
In a French nationwide cohort of patients aged 65 years or older, surviving an index hospitalization for HF in 2015 (N = 70,657), we studied HF readmission predictors available in administrative data, distinguishing HF severity from overall morbidity and taking into account the competing mortality risk, over a 1-year follow-up period. We also computed cumulative incidences and daily rates of HF readmission for patient groups defined according to HF severity and overall morbidity. Of the patients, 31.8% (n = 22,475) were readmitted at least once for HF, and 17.6% (n = 12,416) died without any readmission for HF. HF severity and overall morbidity were the strongest readmission predictors were the strongest readmission predictors (subdistribution hazard ratios 2.66 [95% CI: 2.52-2.81] and 1.37 [1.30-1.45], respectively, when comparing extreme categories). Overall morbidity and age were more strongly associated with the rate of death without HF readmission (cause-specific hazard ratios). The difference in observed HF readmission between patient risk groups was approximately 40% (21.9%, n = 2144/9,786 vs 60.4%, n = 618/1023).
Conclusions
Segmentation of HF patients into readmission risk groups is possible by using administrative data, and it enables the targeting of preventive interventions.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 27 Feb 2021; 27:266-276
Constantinou P, Pelletier-Fleury N, Olié V, Gastaldi-Ménager C, JuillÈre Y, Tuppin P
J Card Fail: 27 Feb 2021; 27:266-276 | PMID: 32801005
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Impact:
Abstract

Cognition, Physical Function, and Quality of Life in Older Patients With Acute Decompensated Heart Failure.

Pastva AM, Hugenschmidt CE, Kitzman DW, Nelson MB, ... Chen H, Duncan PW
Background
Older adults with acute decompensated heart failure have persistently poor clinical outcomes. Cognitive impairment (CI) may be a contributing factor. However, the prevalence of CI and the relationship of cognition with other patient-centered factors such a physical function and quality of life (QOL) that also may contribute to poor outcomes are incompletely understood.
Methods and results
Older (≥60 years) hospitalized patients with acute decompensated heart failure were assessed for cognition (Montreal Cognitive Assessment [MoCA]), physical function (Short Physical Performance Battery [SPPB], 6-minute walk distance [6MWD]), and QOL (Kansas City Cardiomyopathy Questionnaire, Short Form-12). Among patients (N = 198, 72.1 ± 7.6 years), 78% screened positive for CI (MoCA of <26) despite rare medical record documentation (2%). Participants also had severely diminished physical function (SPPB 6.0 ± 2.5 units, 6MWD 186 ± 100 m) and QOL (scores of <50). MoCA positively related to SPPB (ß = 0.47, P < .001), 6MWD ß = 0.01, P = .006) and inversely related to Kansas City Cardiomyopathy Questionnaire Overall Score (ß = -0.05, P < .002) and Short Form-12 Physical Component Score (ß = -0.09, P = .006). MoCA was a small but significant predictor of the results on the SPPB, 6MWD, and Kansas City Cardiomyopathy Questionnaire.
Conclusions
Among older hospitalized patients with acute decompensated heart failure, CI is highly prevalent, is underrecognized clinically, and is associated with severe physical dysfunction and poor QOL. Formal screening may reduce adverse events by identifying patients who may require more tailored care.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 27 Feb 2021; 27:286-294
Pastva AM, Hugenschmidt CE, Kitzman DW, Nelson MB, ... Chen H, Duncan PW
J Card Fail: 27 Feb 2021; 27:286-294 | PMID: 32956816
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Impact:
Abstract

The Differential Impact of the Left Atrial Pressure Components on Pulmonary Arterial Compliance-Resistance Relationship in Heart Failure.

Najjar E, Lund LH, Hage C, Nagy AI, Johnson J, Manouras A
Background
An increase in the pulmonary capillary wedge pressure (PAWP) has been shown to impact on the inherent relationship between the pulmonary arterial compliance (PAC) and pulmonary vascular resistance (PVR), thus augmenting the pulsatile relative to the resistive load of the right ventricle. However, the PAWP comprises the integration of both the steady and the pulsatile pressure components. We sought to address the differential impact of the these distinct PAWP components on the PAC-PVR relationship in a cohort of patients with heart failure.
Methods and results
The study population consisted of 192 patients with hemodynamic findings diagnostic for heart failure. Off-line analysis was performed using the MATLAB software. The steady and pulsatile PAWP components were calculated as mid-A pressure and mean pressure during the V-wave oscillation, respectively. The PAC and PVR were hyperbolically and inversely associated and the subgroup of patients with PAWP above the median (>18 mm Hg) displayed a significant left and downward shift of the curve fit (P < .001). The shift in the PAC-PVR fit between patients with higher versus low steady PAWP was not significant (P = .43). In contrast, there was a significant downward and leftward shift of the PVR-PAC curve fit for the subgroup with a higher pulsatile PAWP (P < .001). Furthermore, only the pulsatile PAWP was significantly associated with the time-constant of the pulmonary circulation, assessed as the PAC × PVR product (P < .001).
Conclusions
In patients with heart failure, the pulsatile rather than the steady PAWP component stands for the previously documented shift of the PAC-PVR relationship occurring at an elevated PAWP.

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

J Card Fail: 27 Feb 2021; 27:277-285
Najjar E, Lund LH, Hage C, Nagy AI, Johnson J, Manouras A
J Card Fail: 27 Feb 2021; 27:277-285 | PMID: 32956814
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Impact:
Abstract

Contemporary Use of Venoarterial Extracorporeal Membrane Oxygenation: Insights from the Multicenter RESCUE Registry.

Loungani RS, Fudim M, Ranney D, Kochar A, ... DeVore AD, Daneshmand M
Background
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a life-saving therapy for patients with cardiovascular collapse, but identifying patients unlikely to benefit remains a challenge.
Methods and results
We created the RESCUE registry, a retrospective, observational registry of adult patients treated with VA-ECMO between January 2007 and June 2017 at 3 high-volume centers (Columbia University, Duke University, and Washington University) to describe short-term patient outcomes. In 723 patients treated with VA-ECMO, the most common indications for deployment were postcardiotomy shock (31%), cardiomyopathy (including acute heart failure) (26%), and myocardial infarction (17%). Patients frequently suffered in-hospital complications, including acute renal dysfunction (45%), major bleeding (41%), and infection (33%). Only 40% of patients (n = 290) survived to discharge, with a minority receiving durable cardiac support (left ventricular assist device [n = 48] or heart transplantation [n = 7]). Multivariable regression analysis identified risk factors for mortality on ECMO as older age (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.12-1.42) and female sex (OR, 1.44; 95% CI, 1.02-2.02) and risk factors for mortality after decannulation as higher body mass index (OR 1.17; 95% CI, 1.01-1.35) and major bleeding while on ECMO support (OR, 1.92; 95% CI, 1.23-2.99).
Conclusions
Despite contemporary care at high-volume centers, patients treated with VA-ECMO continue to have significant in-hospital morbidity and mortality. The optimization of outcomes will require refinements in patient selection and improvement of care delivery.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 27 Feb 2021; 27:327-337
Loungani RS, Fudim M, Ranney D, Kochar A, ... DeVore AD, Daneshmand M
J Card Fail: 27 Feb 2021; 27:327-337 | PMID: 33347997
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Impact:
Abstract

Fibroblast Growth Factor 23 and Exercise Capacity in Heart Failure with Preserved Ejection Fraction.

Ghuman J, Cai X, Patel RB, Khan SS, ... Isakova T, Mehta R
Background
Heart failure with preserved ejection fraction (HFpEF) is characterized by left ventricular hypertrophy and decreased exercise capacity. Fibroblast growth factor 23 (FGF23), a hormone involved in phosphate, vitamin D, and iron homeostasis, is linked to left ventricular hypertrophy and HF. We measured c-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels and examined their associations with exercise capacity in patients with HFpEF.
Methods and results
Using multivariable linear regression and linear mixed models, we studied the associations of cFGF23 and iFGF23 with baseline and mean weekly change over 24 weeks in peak oxygen consumption and 6-minute walk distance in individuals enrolled in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF trial. Our study population included 172 individuals with available plasma for cFGF23 and iFGF23 measurements. Median (25th-75th percentile) baseline cFGF23 and iFGF23 levels were 208.7 RU/mL (132.1-379.5 RU/mL) and 90.3 pg/mL (68.6-128.5 pg/mL), respectively. After adjustment for cardiovascular disease and hematologic and kidney parameters, higher cFGF23 was independently associated with a lower peak oxygen consumption at baseline. Higher iFGF23 was independently associated with shorter 6-minute walk distance at baseline. No significant associations were appreciated with the longitudinal outcomes.
Conclusions
In patients with HFpEF, higher FGF23 levels are independently associated with decreased exercise capacity at baseline.

Published by Elsevier Inc.

J Card Fail: 27 Feb 2021; 27:309-317
Ghuman J, Cai X, Patel RB, Khan SS, ... Isakova T, Mehta R
J Card Fail: 27 Feb 2021; 27:309-317 | PMID: 33035687
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Impact:
Abstract

Plasma Volume Status and Its Association With In-Hospital and Postdischarge Outcomes in Decompensated Heart Failure.

Fudim M, Lerman JB, Page C, Alhanti B, ... O\'connor CM, Mentz RJ
Background
Prior analyses suggest an association between formula-based plasma volume (PV) estimates and outcomes in heart failure (HF). We assessed the association between estimated PV status by the Duarte-ePV and Kaplan Hakim (KH-ePVS) formulas, and in-hospital and postdischarge clinical outcomes, in the ASCEND-HF trial.
Methods and results
The KH-ePVS and Duarte-ePV were calculated on admission. We assessed associations with in-hospital worsening HF, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality. There were 6373 (89.2%), and 6354 (89.0%) patients who had necessary characteristics to calculate KH-ePVS and Duarte-ePV, respectively. There was no association between PV by either formula with in-hospital worsening HF. KH-ePVS showed a weak correlation with N-terminal prohormone BNP, and with measures of decongestion such as body weight change and urine output (r < 0.3 for all). Duarte-ePV was trending toward an association with worse 30-day (adjusted odds ratio 1.07, 95% confidence interval [CI] 1.00-1.15, P = .058), but not 180-day outcomes (adjusted hazard ratio 1.03, 95% CI 0.97-1.09, P = .289). A continuous KH-ePVS of >0 (per 10-unit increase) was associated with improved 30-day outcomes (adjusted odds ratio 0.75, 95% CI 0.62-0.91, P = .004). The continuous KH-ePVS was not associated with 180-day outcomes (adjusted hazard ratio 1.05, 95% CI 0.98-1.12, P = .139).
Conclusions
Baseline PV estimates had a weak association with in-hospital measures of decongestion. The Duarte-ePV trended toward an association with early clinical outcomes in decompensated HF, and may improve risk stratification in HF.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 27 Feb 2021; 27:297-308
Fudim M, Lerman JB, Page C, Alhanti B, ... O'connor CM, Mentz RJ
J Card Fail: 27 Feb 2021; 27:297-308 | PMID: 33038532
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Impact:
Abstract

Resting Heart Rate as an Important Predictor of Mortality and Morbidity in Ambulatory Patients With Heart Failure: A Systematic Review and Meta-Analysis.

Lau K, Malik A, Foroutan F, Buchan TA, ... Orchanian-Cheff A, Alba AC
Background
Resting heart rate is a risk factor of adverse heart failure outcomes; however, studies have shown controversial results. This meta-analysis evaluates the association of resting heart rate with mortality and hospitalization and identifies factors influencing its effect.
Methods and results
We systematically searched electronic databases in February 2019 for studies published in 2005 or before that evaluated the resting heart rate as a primary predictor or covariate of multivariable models of mortality and/or hospitalization in adult ambulatory patients with heart failure. Random effects inverse variance meta-analyses were performed to calculate pooled hazard ratios. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess evidence quality. Sixty-two studies on 163,445 patients proved eligible. Median population heart rate was 74 bpm (interquartile range 72-76 bpm). A 10-bpm increase was significantly associated with increased risk of all-cause mortality (hazard ratio 1.10, 95% confidence interval 1.08-1.13, high quality). Overall, subgroup analyses related to patient characteristics showed no changes to the effect estimate; however, there was a strongly positive interaction with age showing increasing risk of all-cause mortality per 10 bpm increase in heart rate.
Conclusions
High-quality evidence demonstrates increasing resting heart rate is a significant predictor of all-cause mortality in ambulatory patients with heart failure on optimal medical therapy, with consistent effect across most patient factors and an increased risk trending with older age.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 27 Feb 2021; 27:349-363
Lau K, Malik A, Foroutan F, Buchan TA, ... Orchanian-Cheff A, Alba AC
J Card Fail: 27 Feb 2021; 27:349-363 | PMID: 33171294
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Impact:
Abstract

Prognostic Understanding and Preference for the Communication Process with Physicians in Hospitalized Heart Failure Patients.

Kitakata H, Kohno T, Kohsaka S, Fujisawa D, ... Yuasa S, Fukuda K
Background
Heart failure (HF) is a highly prevalent, heterogeneous, and life-threatening condition. Precise prognostic understanding is essential for effective decision making, but little is known about patients\' attitudes toward prognostic communication with their physicians.
Methods and results
We conducted a questionnaire survey, consisting of patients\' prognostic understanding, preferences for information disclosure, and depressive symptoms, among hospitalized patients with HF (92 items in total). Individual 2-year survival rates were calculated using the Seattle Heart Failure Model, and its agreement level with patient self-expectations of 2-year survival were assessed. A total of 113 patients completed the survey (male 65.5%, median age 75.0 years, interquartile range 66.0-81.0 years). Compared with the Seattle Heart Failure Model prediction, patient expectation of 2-year survival was matched only in 27.8% of patients; their agreement level was low (weighted kappa = 0.11). Notably, 50.9% wished to know \"more,\" although 27.7% felt that they did not have an adequate prognostic discussion. Compared with the known prognostic variables (eg, age and HF severity), logistic regression analysis demonstrated that female and less depressive patients were associated with patients\' preference for \"more\" prognostic discussion.
Conclusions
Patients\' overall prognostic understanding was suboptimal. The communication process requires further improvement for patients to accurately understand their HF prognosis and be involved in making a better informed decision.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 27 Feb 2021; 27:318-326
Kitakata H, Kohno T, Kohsaka S, Fujisawa D, ... Yuasa S, Fukuda K
J Card Fail: 27 Feb 2021; 27:318-326 | PMID: 33171293
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Impact:
Abstract

Implantation of an Atrial Flow Regulator in a Child on Venoarterial Extracorporeal Membrane Oxygenator as a Bridge to Heart Transplant: A Case Report.

Piccinelli E, Castro-Verdes MB, Fraisse A, Bautista-Rodriguez C
Background
Balloon dilation and stenting of the atrial septum are techniques used to unload left heart cavities in acute or end-stage heart failure in children. However, they carry significant risks such as tamponade or device embolization.
Case presentation
We report the first case of a child with an end-stage mitochondrial cardiomyopathy on a venoarterial extracorporeal membrane oxygenator as a bridge to heart transplant where an atrial flow regulator device has been implanted.
Conclusions
This case illustrates the feasibility and safety of atrial flow regulator implantation in this setting. This procedure allowed to wean inotropic support while awaiting heart transplantation.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 27 Feb 2021; 27:364-367
Piccinelli E, Castro-Verdes MB, Fraisse A, Bautista-Rodriguez C
J Card Fail: 27 Feb 2021; 27:364-367 | PMID: 33242607
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Impact:
Abstract

Bariatric Surgery in Patients with Obesity and Ventricular Assist Devices Considered for Heart Transplantation: Systematic Review and Individual Participant Data Meta-analysis.

daSilva-deAbreu A, Alhafez BA, Curbelo-Pena Y, Lavie CJ, ... Loro-Ferrer JF, Mandras SA
Background
Class II obesity (body mass index BMI ≥35 kg/m2) is a contraindication to heart transplantation (HT). Although few single-center studies (case reports/series and small cohorts) have reported promising outcomes of bariatric surgery (BS) in patients with obesity and ventricular assist devices, low sample sizes have made their analysis and interpretation challenging.
Methods and results
We conducted a systematic search in ClinicalTrials.gov, Cochrane, Embase, PubMed, Google Scholar, and most relevant bariatric and heart failure journals. We extracted baseline and outcome individual participant data for every ventricular assist device patient undergoing BS with reported postoperative BMI and their respective timepoints when BMI data were measured. Fourteen references with 29 patients were included. The mean age was 41.9 ± 12.2 years, 82.8% underwent laparoscopic sleeve gastrectomy, and 39.3% had reported perioperative adverse events. The mean pre-BS BMI was 45.5 ± 6.6 kg/m2 and decreased significantly during follow-up (rho -0.671; P< .00001). Among 23 patients with documented listing status, 78.3% were listed for HT. Thirteen of 28 patients (46.4%) underwent HT at 14.4 ± 7.0 months. There were no reported deaths for the HT-free 1-year period. Median follow-up was 24 months (interquartile range, 12-30 months). Twenty-two of 28 patients (78.6%) achieved the composite outcome (BMI of<35 kg/m2/HT/listing for HT/myocardial recovery) at 11 months (interquartile range, 3-17 months). Patients with a BMI<45 kg/m2 had a higher chance of achieving the composite outcome (P< .003).
Conclusions
BS may help patients with obesity and ventricular assist devices to lose a significant amount of weight and improve their candidacy for HT or even achieve myocardial recovery.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 27 Feb 2021; 27:338-348
daSilva-deAbreu A, Alhafez BA, Curbelo-Pena Y, Lavie CJ, ... Loro-Ferrer JF, Mandras SA
J Card Fail: 27 Feb 2021; 27:338-348 | PMID: 33358959
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Impact:
Abstract

Acute Hemodynamic Effects of Sacubitril-Valsartan In Heart Failure Patients Receiving Intravenous Vasodilator and Inotropic Therapy.

Martyn T, Faulkenberg KD, Albert CL, Il\'giovine ZJ, ... Wilson Tang WH, Starling RC
Background
Prior study has demonstrated that transitioning patients in acutely decompensated heart failure with a low cardiac output directly from intravenous (i.v.) vasoactive (ie, vasodilators or inotropes) drugs to sacubitril-valsartan (S/V) can be done safely with tolerance to the 1-month follow-up. Here, we further characterize the hemodynamic impact of S/V after patients have been optimized on vasoactive therapy.
Methods and results
In a single-center, retrospective analysis, 25 patients with cardiac index of less than 2.2 L/min/m2 were admitted to the cardiac intensive care unit and newly initiated on angiotensin receptor-neprilysin inhibitor therapy with the guidance of invasive hemodynamic monitoring. Hemodynamic data were gathered and compared upon cardiac intensive care unit admission, after optimization with i.v. vasoactive therapy, and after S/V initiation and weaning off i.v.
Therapy
All patients who tolerated S/V (n = 20) were weaned off vasoactive medications before transfer out of cardiac intensive care unit. Patients maintained their significant improvement in cardiac index and reduction in SVR/PVR on transition from i.v. inotropic and vasodilator therapy to oral S/V. There was an increase in pulmonary artery pulsatility index with S/V therapy compared with the i.v. vasoactive phase of care.
Conclusions
Patients in the cardiac intensive care unit can be successfully bridged from vasoactive i.v. therapy to oral S/V with sustained improvement in cardiac index garnered from vasoactive agents. We also observed improvement in the pulmonary artery pulsatility index and maintenance of left and right ventricular unloading with S/V. These encouraging findings merit further prospective study.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 27 Feb 2021; 27:368-372
Martyn T, Faulkenberg KD, Albert CL, Il'giovine ZJ, ... Wilson Tang WH, Starling RC
J Card Fail: 27 Feb 2021; 27:368-372 | PMID: 33358957
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Abstract

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

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

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 25 Feb 2021; epub ahead of print
Zern EK, Ho JE, Panah LG, Lau ES, ... Nayor M, Lewis GD
J Card Fail: 25 Feb 2021; epub ahead of print | PMID: 33647476
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Abstract

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

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

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

J Card Fail: 25 Feb 2021; epub ahead of print
Faxen UL, Venkateshvaran A, Shah SJ, Lam CSP, ... Hage C, Lund LH
J Card Fail: 25 Feb 2021; epub ahead of print | PMID: 33647474
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Abstract

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

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

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 24 Feb 2021; epub ahead of print
Gonzalez MH, Wang Q, Yaranov DM, Albert C, ... Starling RC, Joyce E
J Card Fail: 24 Feb 2021; epub ahead of print | PMID: 33640481
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Abstract

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

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

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 23 Feb 2021; epub ahead of print
Baman JR, Patil KD, Medhekar AN, Wilcox JE
J Card Fail: 23 Feb 2021; epub ahead of print | PMID: 33636331
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Abstract

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

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

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 23 Feb 2021; epub ahead of print
Rosenblum H, Pinsino A, Zuver A, Javaid A, ... Colombo PC, Stöhr EJ
J Card Fail: 23 Feb 2021; epub ahead of print | PMID: 33639317
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Abstract

Universal Definition and Classification of Heart Failure.

Bozkurt B, Coats A, Tsutsui H
In this document, we propose a universal definition of heart failure (HF) as the following: HF is a clinical syndrome with symptoms and or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and or objective evidence of pulmonary or systemic congestion. We propose revised stages of HF as: At-risk for HF (Stage A) , for patients at risk for HF but without current or prior symptoms or signs of HF and without structural or biomarkers evidence of heart disease. Pre-heart failure (Stage B) for patients without current or prior symptoms or signs of HF but evidence of structural heart disease or abnormal cardiac function, or elevated natriuretic peptide levels. HF (Stage C) for patients with current or prior symptoms and/or signs of HF caused by a structural and/or functional cardiac abnormality. Advanced HF (Stage D) for patients with severe symptoms and/ or signs of HF at rest, recurrent hospitalizations despite guideline-directed management and therapy (GDMT) , refractory or intolerant to GDMT, requiring advanced therapies such as consideration for transplant, mechanical circulatory support, or palliative care. Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF) . The classification includes HF with reduced EF (HFrEF) : HF with LVEF ≤ 40%; HF with mid-range EF (HFmrEF) : HF with LVEF 41-49%; HF with preserved EF (HFpEF) : HF with LVEF ≥ 50%; and HF with improved EF (HFimpEF) : HF with a baseline LVEF ≤ 40%, a ≥ 10 point increase from baseline LVEF, and a second measurement of LVEF > 40.

Published by Elsevier Inc.

J Card Fail: 06 Feb 2021; epub ahead of print
Bozkurt B, Coats A, Tsutsui H
J Card Fail: 06 Feb 2021; epub ahead of print | PMID: 33662581
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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: 04 Feb 2021; epub ahead of print
Ghio S, Crimi G, Houston B, Montalto C, ... D'alto M, Tedford RJ
J Card Fail: 04 Feb 2021; epub ahead of print | PMID: 33556547
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Impact:
Abstract

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

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

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 04 Feb 2021; epub ahead of print
Miller PE, Van Diepen S, Metkus TS, Alviar CL, ... Desai NR, Ahmad T
J Card Fail: 04 Feb 2021; epub ahead of print | PMID: 33556546
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Abstract

Pregnancy after Heart Transplantation.

Defilippis EM, Kittleson MM
As post-transplant survival improves, many heart transplant (HT) recipients are of, or are surviving to, childbearing age. Solid-organ transplant recipients who become pregnant should be managed by a multidisciplinary cardio-obstetrics team, including specialists in maternal and fetal medicine, cardiology and transplant medicine, as well as anesthesia, neonatology, psychology, genetics, and social services. With careful patient selection, pregnancy after HT can been managed safely. The purpose of this comprehensive review was to summarize the current evidence and recommendations surrounding preconception counseling, medical management and surveillance, maternal outcomes, breastfeeding, and remaining gaps in knowledge.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jan 2021; 27:176-184
Defilippis EM, Kittleson MM
J Card Fail: 30 Jan 2021; 27:176-184 | PMID: 32771397
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Abstract

H2FPEF Score Reflects the Left Atrial Strain and Predicts Prognosis in Patients With Heart Failure With Preserved Ejection Fraction.

Hwang IC, Cho GY, Choi HM, Yoon YE, ... Kim HK, Kim YJ
Background
The H2FPEF score is a validated algorithm for the diagnosis of heart failure with preserved ejection fraction (HFpEF). We investigated the associations of the H2FPEF score with echocardiographic parameters and prognosis in patients with HFpEF admitted for acute heart failure.
Methods and results
In total, 4312 patients at 3 tertiary centers were identified. Among 1335 patients with HFpEF, the H2FPEF score was available in 1105 patients (39% male) with a median age of 77 years (interquartile range 69-82). The median H2FPEF score was 4 (interquartile range 3-6). Patients with higher H2FPEF scores had worse left atrial (LA) size, peak atrial longitudinal strain of the left atrium, mitral E/e\' ratio, and peak tricuspid regurgitation velocity. Peak atrial longitudinal strain of the left atrium demonstrated a significant association with the H2FPEF score, in patients without atrial fibrillation and those without atrial fibrillation. After adjustment for clinical factors and echocardiographic parameters, patients with higher H2FPEF scores had a higher risk of mortality and hospitalization for heart failure, regardless of the presence of atrial fibrillation.
Conclusions
The H2FPEF score reflects left atrial function in patients with HFpEF admitted for acute heart failure. This association supports the clinical usefulness of the H2FPEF score as an indicator of diastolic dysfunction, a diagnostic algorithm for HFpEF, and a prognostic factor in patients with HFpEF.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jan 2021; 27:198-207
Hwang IC, Cho GY, Choi HM, Yoon YE, ... Kim HK, Kim YJ
J Card Fail: 30 Jan 2021; 27:198-207 | PMID: 33035685
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Abstract

Vagus Nerve Stimulation Provides Multiyear Improvements in Autonomic Function and Cardiac Electrical Stability in the ANTHEM-HF Study.

Nearing BD, Anand IS, Libbus I, Dicarlo LA, Kenknight BH, Verrier RL
Background
Patients with heart failure with reduced left ventricular ejection fraction (LVEF) (HFrEF) experience long-term deterioration of autonomic function and cardiac electrical stability linked to increased mortality risk. The Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Heart Failure (ANTHEM-HF) trial reported improved heart rate variability (HRV) and heart rate turbulence (HRT) and reduced T-wave alternans (TWA) after 12 months of vagus nerve stimulation (VNS). We investigated whether the benefits of chronic VNS persist in the long term.
Methods and results
Effects of chronic VNS on heart rate, HRV, HRT, TWA, R-wave and T-wave heterogeneity (RWH, TWH), and nonsustained ventricular tachycardia (NSVT) incidence were evaluated in all ANTHEM-HF patients with ambulatory ECG data at 24 and 36 months (n = 25). Autonomic markers improved significantly at 24 and 36 months compared to baseline [heart rate, square root of the mean squared differences of successive normal-to-normal intervals (rMSSD), standard deviation of the normal-to-normal intervals (SDNN), HF-HRV, HRT slope, P < 0.05]. Peak TWA levels remained reduced at 24 and 36 months (P < 0.0001). Reductions in RWH and TWH at 6 and 12 months persisted at 24 and 36 months (P < 0.01). NSVT decreased at 12, 24, and 36 months (P < 0.025). No sudden cardiac deaths, ventricular fibrillation, or sustained ventricular tachycardia occurred.
Conclusion
In symptomatic patients with HFrEF, chronic VNS appears to confer wide-ranging, persistent improvements in autonomic tone (HRV), baroreceptor sensitivity (HRT), and cardiac electrical stability (TWA, RWH, TWH).

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

J Card Fail: 30 Jan 2021; 27:208-216
Nearing BD, Anand IS, Libbus I, Dicarlo LA, Kenknight BH, Verrier RL
J Card Fail: 30 Jan 2021; 27:208-216 | PMID: 33049374
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Abstract

Inclusion of Performance Parameters and Patient Context in the Clinical Practice Guidelines for Heart Failure.

Goyal P, Unlu O, Kennel PJ, Schumacher RC, ... Rich MW, Makam A
Background
To facilitate evidence-based medicine (EBM) on an individual level, it may be important for clinical practice guidelines (CPGs) to incorporate the performance parameters of diagnostic studies and therapeutic interventions (such as likelihood ratio and absolute benefit or harm), and to incorporate relevant patient contexts that may influence decision-making. We sought to determine the extent to which heart failure CPGs currently incorporate this information.
Methods
We reviewed the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) 2013 Heart Failure CPG, the 2017 ACCF/AHA/HFSA update, and European Society of Cardiology (ESC) 2016 Heart Failure CPG. We abstracted variables for each CPG recommendation from the following domains: quality of evidence, strength of recommendation, diagnostic and therapeutic performance parameters, and patient context.
Results
We examined 169 recommendations from the ACCF/AHA 2013 CPGs and 2017 update and 187 recommendations from the 2016 ESC CPGs. Performance parameters for diagnostic studies (2013 ACCF/AHA: 13%; 2017 ACCF/AHA/HFSA update: 0%; 2016 ESC: 0%) and therapeutic interventions (2013 ACCF/AHA: 65%; 2017 ACCF/AHA/HFSA update: 64%; 2016 ESC: 16%) were not commonly included in CPGs. Patient context was included in about half of ACCF/AHA recommendations and a quarter of ESC recommendations.
Conclusions
The majority of recommendations from heart failure CPGs lack information on diagnostic and therapeutic performance parameters and patient context. Given the importance of these components to effectively implement EBM, particularly for a heterogeneous heart failure population, innovative strategies are needed to optimize CPGs so they provide comprehensive yet succinct recommendations that can improve population-level outcomes and ensure optimal patient-centered care.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jan 2021; 27:190-197
Goyal P, Unlu O, Kennel PJ, Schumacher RC, ... Rich MW, Makam A
J Card Fail: 30 Jan 2021; 27:190-197 | PMID: 33065263
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Abstract

Ranolazine Improves Right Ventricular Function in Patients With Precapillary Pulmonary Hypertension: Results From a Double-Blind, Randomized, Placebo-Controlled Trial.

Han Y, Forfia P, Vaidya A, Mazurek JA, ... Chan SY, Waxman AB
Introduction
A major outcome determinant in patients with precapillary pulmonary hypertension (PH) is right ventricular (RV) function. We studied the effect of ranolazine on RV function over 6 months using cardiovascular magnetic resonance (CMR) imaging in patients with precapillary PH (groups I, III, and IV).
Methods and results
We enrolled patients with PH and RV dysfunction (CMR imaging ejection fraction [EF] of <45%) in a longitudinal, randomized, double-blinded, placebo controlled, multicenter study of ranolazine treatment. All enrolled patients were on stable PH-specific therapy. Enrolled patients were assessed using CMR imaging, New York Heart Association functional class, N-terminal pro brain natriuretic peptide, 6-minute walk test, and quality of life health outcomes at baseline and repeated at the end of treatment. The primary outcome was change in RVEF after 6 months of treatment. Analysis of covariance was used to analyze the longitudinal changes taking into account baseline values, age, and sex, based on per protocol population. Twenty-two patients were enrolled, and 9 patients completed follow-up CMR imaging after ranolazine treatment and 6 completed placebo treatment. There was significant increase in RVEF at end of treatment compared with baseline in the ranolazine group adjusted for baseline values, age, and sex. There were no statistically significant changes in secondary outcomes such as changes in New York Heart Association functional class, 6-minute walk distance, N-terminal pro brain natriuretic peptide, or quality of life measures. Ranolazine treated patients experienced a higher number of adverse events, but only one was discontinued owing to side effects.
Conclusions
Ranolazine may improve RV function in patients with precapillary PH. Larger studies are needed to confirm the beneficial effects of ranolazine.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jan 2021; 27:253-257
Han Y, Forfia P, Vaidya A, Mazurek JA, ... Chan SY, Waxman AB
J Card Fail: 30 Jan 2021; 27:253-257 | PMID: 33223140
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Impact:
Abstract

When the At-Risk Do Not Develop Heart Failure: Understanding Positive Deviance Among Postmenopausal African American and Hispanic Women.

Breathett K, Kohler LN, Eaton CB, Franceschini N, ... Shadyab AH, Cené CW
Background
African American and Hispanic postmenopausal women have the highest risk for heart failure compared with other races, but heart failure prevalence is lower than expected in some national cohorts. It is unknown whether psychosocial factors are associated with lower risk of incident heart failure hospitalization among high-risk postmenopausal minority women.
Methods and results
Using the Women\'s Health Initiative Study, African American and US Hispanic women were classified as high-risk for incident heart failure hospitalization with 1 or more traditional heart failure risk factors and the highest tertile heart failure genetic risk scores. Positive psychosocial factors (optimism, social support, religion) and negative psychosocial factors (living alone, social strain, depressive symptoms) were measured using validated survey instruments at baseline. Adjusted subdistribution hazard ratios of developing heart failure hospitalization were determined with death as a competing risk. Positive deviance indicated not developing incident heart failure hospitalization with 1 or more risk factors and the highest tertile for genetic risk. Among 7986 African American women (mean follow-up of 16 years), 27.0% demonstrated positive deviance. Among high-risk African American women, optimism was associated with modestly reduced risk of heart failure hospitalization (subdistribution hazard ratio 0.94, 95% confidence interval 0.91-0.99), and social strain was associated with modestly increased risk of heart failure hospitalization (subdistribution hazard ratio 1.07, 95% confidence interval 1.02-1.12) in the initial models; however, no psychosocial factors were associated with heart failure hospitalization in fully adjusted analyses. Among 3341 Hispanic women, 25.1% demonstrated positive deviance. Among high-risk Hispanic women, living alone was associated with increased risk of heart failure hospitalization (subdistribution hazard ratio 1.97, 95% confidence interval 1.06-3.63) in unadjusted analyses; however, no psychosocial factors were associated with heart failure hospitalization in fully adjusted analyses.
Conclusions
Among postmenopausal African American and Hispanic women, a significant proportion remained free from heart failure hospitalization despite having the highest genetic risk profile and 1 or more traditional risk factors. No observed psychosocial factors were associated with incident heart failure hospitalization in high-risk African Americans and Hispanics. Additional investigation is needed to understand protective factors among high-risk African American and Hispanic women.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jan 2021; 27:217-223
Breathett K, Kohler LN, Eaton CB, Franceschini N, ... Shadyab AH, Cené CW
J Card Fail: 30 Jan 2021; 27:217-223 | PMID: 33232822
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Impact:
Abstract

Dual Vasopressin Receptor Antagonism to Improve Congestion in Patients With Acute Heart Failure: Design of the AVANTI Trial.

Goldsmith SR, Burkhoff D, Gustafsson F, Voors A, ... Dinh W, Udelson JE
Background
Loop diuretics are the main treatment for patients with acute heart failure, but are associated with neurohormonal stimulation and worsening renal function and do not improve long-term outcomes. Antagonists to arginine vasopressin may provide an alternative strategy to avoid these effects. The AVANTI study will investigate the efficacy and safety of pecavaptan, a novel, balanced dual-acting V1a/V2 vasopressin antagonist, both as adjunctive therapy to loop diuretics after admission for acute heart failure, and later as monotherapy.
Methods and results
AVANTI is a double-blind, randomized phase II study in 571 patients hospitalized with acute heart failure and signs of persistent congestion before discharge. In part A, patients will receive either pecavaptan 30 mg/d or placebo with standard of care for 30 days. In part B, eligible patients will continue treatment or receive pecavaptan or diuretics as monotherapy for another 30 days. The primary end points for part A are changes in body weight and serum creatinine; for part B, changes in body weight and blood urea nitrogen/creatinine ratio.
Conclusions
This study will provide the first evidence that a balanced V1a/V2 antagonist may safely enhance decongestion, both as an adjunct to loop diuretics and as an alternative strategy.
Trial registration number
NCT03901729.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

J Card Fail: 30 Jan 2021; 27:233-241
Goldsmith SR, Burkhoff D, Gustafsson F, Voors A, ... Dinh W, Udelson JE
J Card Fail: 30 Jan 2021; 27:233-241 | PMID: 33188886
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Impact:
Abstract

Acute Unloading Effects of Sildenafil Enhance Right Ventricular-Pulmonary Artery Coupling in Heart Failure.

Monzo L, Reichenbach A, Al-Hiti H, Borlaug BA, ... Kautzner J, Melenovsky V
Background
Phosphodiesterase-5A inhibitors (PDE5i) are sometimes used in patients with advanced heart failure with reduced ejection fraction before heart transplant or left ventricular assist device implantation to decrease right ventricular (RV) afterload and mitigate the risk of right heart failure. Conflicting evidence exists regarding the impact of these drugs on RV contractility. The aim of this study was to explore the acute effects of PDE5i on ventricular-vascular coupling and load-independent RV contractility.
Methods
Twenty-two patients underwent right heart catheterization and gated equilibrium blood pool single photon emission computed tomography, before and after 20 mg intravenous sildenafil. Single photon emission computed tomography and right heart catheterization-derived data were used to calculate RV loading and contractility.
Results
PDE5i induced a decrease in the right atrial pressure (-43%), pulmonary artery (PA) mean pressure (-26%), and PA wedge pressure (PAWP; -23%), with favorable reductions in pulmonary vascular resistance (-41%) and PA elastance (-40%), and increased cardiac output (+13%) (all P < 0.01). The RV ejection fraction increased with sildenafil (+20%), with no change of RV contractility (P = 0.74), indicating that the improvement in the RV ejection fraction was related to enhanced RV-PA coupling (r = 0.59, P = 0.004) by a decrease in the ventricular load. RV diastolic compliance increased with sildenafil. The decrease in the PAWP correlated with RV end-diastolic volume decrease; no relationship was observed with the change in LV transmural pressure, suggesting decreased pericardial constraint.
Conclusions
Acute PDE5i administration has profound RV afterload-reducing effects, improves the RVEF, decreases RV volumes, and decreases the PAWP, predominantly through relief of pericardial constraint, without effects on RV chamber contractility. These findings support further study of PDE5i in protection of RV function in advanced heart failure with reduced ejection fraction who are at risk of RV failure.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jan 2021; 27:224-232
Monzo L, Reichenbach A, Al-Hiti H, Borlaug BA, ... Kautzner J, Melenovsky V
J Card Fail: 30 Jan 2021; 27:224-232 | PMID: 33232820
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Abstract

Intravenous Infusion of the β-Adrenergic Receptor Antagonist APD418 Improves Left Ventricular Systolic Function in Dogs With Systolic Heart Failure.

Sabbah HN, Zhang K, Gupta RC, Xu J, ... Nguyen N, Adams J
Background
Unlike β1- and β2-adrenergic receptors (ARs), β3-AR stimulation inhibits cardiac contractility and relaxation. In the failing left ventricular (LV) myocardium, β3-ARs are upregulated, and can be maladaptive in the setting of decompensation by contributing to LV dysfunction. This study examined the effects of intravenous infusions of the β3-AR antagonist APD418 on cardiovascular function and safety in dogs with systolic heart failure (HF).
Methods and results
Three separate studies were performed in 21 dogs with coronary microembolization-induced HF (LV ejection fraction [LVEF] of approximately 35%). Studies 1 and 2 (n = 7 dogs each) were APD418 dose escalation studies (dosing range, 0.35-15.00 mg/kg/h) designed to identify an effective dose of APD418 to be used in study 3. Study 3, the sustained efficacy study, (n = 7 dogs) was a 6-hour constant intravenous infusion of APD418 at a dose of 4.224 mg/kg (0.70 mg/kg/h) measuring key hemodynamic endpoints (e.g., EF, cardiac output, the time velocity integral of the mitral inflow velocity waveform representing early filling to time-velocity integral representing left atrial contraction [Ei/Ai]). Studies 1 and 2 showed a dose-dependent increase of LVEF and Ei/Ai, the latter being an index of LV diastolic function. In study 3, infusion of APD418 over 6 hours increased LVEF from 31 ± 1% to 38 ± 1% (P < .05) and increased Ei/Ai from 3.4 ± 0.4 to 4.9 ± 0.5 (P < .05). Vehicle had no effect on the LVEF or Ei/Ai. In study 3, APD418 had no significant effects on the HR or the systemic blood pressure.
Conclusions
Intravenous infusions of APD418 in dogs with systolic HF elicit significant positive inotropic and lusitropic effects. These findings support the development of APD418 for the in-hospital treatment of patients with an acute exacerbation of chronic HF.

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jan 2021; 27:242-252
Sabbah HN, Zhang K, Gupta RC, Xu J, ... Nguyen N, Adams J
J Card Fail: 30 Jan 2021; 27:242-252 | PMID: 33352205
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Abstract

Pregnancy Associated Heart Failure With Preserved Ejection Fraction: Risk Factors and Maternal Morbidity.

Briller JE, Mogos MF, Muchira JM, Piano MR
Background
Cardiovascular conditions are leading contributors to increasing maternal morbidity and mortality. Heart failure with preserved ejection fraction (HFpEF) results in the majority of HF admissions in women, yet its impact in pregnancy is unknown. We examined the prevalence rates, risk factors and adverse pregnancy outcomes in women with HFpEF during pregnancy-related hospitalizations in the United States.
Methods and results
We conducted a cross-sectional analysis of pregnancy-related hospitalizations from 2002 through 2014 using the National Inpatient Sample. HFpEF cases were identified using the 428.3 International Classification of Diseases, 9th edition, Clinical Modification code. Weighting variables were used to provide national estimates, unconditional survey logistic regression to generate odds ratios and 95% confidence intervals (CI) representing adjusted associations with adverse pregnancy outcomes and Joinpoint regression to estimate temporal trends. Among 58,732,977 hospitalizations, there were 3840 HFpEF cases, an overall rate of 7 cases per 100,000 pregnancy-related hospitalizations; 56% occurred postpartum, 27% during delivery, and 17% antepartum. The temporal trend for hospitalization increased throughout the timeframe by 19.4% (95% CI 13.9-25.1). HFpEF hospitalizations were more common for Black, older, or poor women. Risk factors included hypertension (chronic hypertension and hypertensive disorders of pregnancy), anemia, obesity, diabetes, renal disease and coronary atherosclerosis; all known risk factors for HFpEF. Women with HFpEF were 2.61-6.47 times more likely to experience adverse pregnancy outcomes.
Conclusions
The pregnancy-related HFpEF hospitalization prevalence has increased and is associated with adverse pregnancy outcomes. Risk factors resemble those outside pregnancy, emphasizing the need for screening and monitoring women with risk factors during pregnancy for HFpEF.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jan 2021; 27:143-152
Briller JE, Mogos MF, Muchira JM, Piano MR
J Card Fail: 30 Jan 2021; 27:143-152 | PMID: 33388469
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Abstract

A Case-Control Study of Peripartum Cardiomyopathy Using the Rochester Epidemiology Project.

Douglass EJ, Cooper LT, Morales-Lara AC, Adedinsewo DA, ... Blauwet LA, Fairweather D
Background
The incidence of peripartum cardiomyopathy (PPCM) is known through referral center databases that may be affected by referral, misclassification, and other biases. We sought to determine the community-based incidence and natural history of PPCM using the Rochester Epidemiology Project.
Methods and results
Incident cases of PPCM occurring between January 1, 1970, and December 31, 2014, were identified in Olmsted County, Minnesota. A total of 15 PPCM cases were confirmed yielding an incidence of 20.3 cases per 100,000 live births in Olmsted County, Minnesota. Clinical information, disease characteristics, and outcomes were extracted from medical records in a 27-county region of the Rochester Epidemiology Project including Olmsted County and matched in a 1:2 ratio with pregnant women without PPCM. A total of 48 women were identified with PPCM in the expanded 27-county region. There was 1 death and no transplants over a median of 7.3 years of follow-up. Six of the 23 women with subsequent pregnancies developed recurrent PPCM, all of whom recovered. Migraine and anxiety were identified as novel possible risk factors for PPCM.
Conclusions
The population-based incidence of PPCM was 20.3 cases per 100,000 live births in Olmsted County, Minnesota. Cardiovascular outcomes were generally excellent in this community cohort.

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

J Card Fail: 30 Jan 2021; 27:132-142
Douglass EJ, Cooper LT, Morales-Lara AC, Adedinsewo DA, ... Blauwet LA, Fairweather D
J Card Fail: 30 Jan 2021; 27:132-142 | PMID: 33388468
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Abstract

Risk Prediction for Peripartum Cardiomyopathy in Delivering Mothers: A Validated Risk Model: PPCM Risk Prediction Model.

Davis MB, Jarvie J, Gambahaya E, Lindenfeld J, Kao D
Background
Peripartum cardiomyopathy (PPCM) causes significant morbidity and mortality in childbearing women. Delays in diagnosis lead to worse outcomes; however, no validated risk prediction model exists. We sought to validate a previously described model and identify novel risk factors for PPCM presenting at the time of delivery.
Methods and results
Administrative hospital records from 5,277,932 patients from 8 states were screened for PPCM, identified by International Classification of Disease-9 Clinical Modification codes (674.5x) at the time of delivery. Demographics, comorbidities, procedures, and outcomes were quantified. Performance of a previously published regression model alone and with the addition of novel PPCM-associated characteristics was assessed using receiver operating characteristic area under the curve (AUC) analysis. Novel risk factors were identified using multivariate logistic regression and the likelihood ratio test. In total, 1186 women with PPCM were studied, including 535 of 4,003,912 delivering mothers (0.013%) in the derivation set compared with 651 of 5,277,932 (0.012%) in the validation set. The previously published risk prediction model performed well in both the derivation (area under the curve 0.822) and validation datasets (area under the curve 0.802). Novel PPCM-associated characteristics in the combined cohort included diabetes mellitus (odds ratio [OR] of PPCM 1.93, 95% confidence interval [CI] 1.23-3.02, P = .004), mood disorders (OR 1.74, 95% CI 1.22-2.47, P = .002), obesity (OR 1.92, 95% CI 1.45-2.55, P < .001), and Medicaid insurance (OR 1.54, 95% CI 1.22-1.96, P < .001).
Conclusions
This is the first validated risk prediction model to identify women at increased risk for PPCM at the time of delivery. Diabetes mellitus, obesity, mood disorders, and lower socioeconomic status are risk factors associated with PPCM. This model may be useful for identifying women at risk and preventing delays in diagnosis.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jan 2021; 27:159-167
Davis MB, Jarvie J, Gambahaya E, Lindenfeld J, Kao D
J Card Fail: 30 Jan 2021; 27:159-167 | PMID: 33388467
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Abstract

Biomarkers and Their Relation to Cardiac Function Late After Peripartum Cardiomyopathy.

Ersbøll AS, Goetze JP, Johansen M, Hauge MG, ... Gustafsson F, Damm P
Background
Angiogenic imbalance involving the placental protein soluble Fms-like tyrosine kinase-1 (sFlt-1) and cleavage of the nursing-hormone prolactin by the enzyme cathepsin D (CD) both play a role in the pathogenesis of peripartum cardiomyopathy (PPCM). We hypothesized that angiogenic imbalance and increased activity of CD have a long-lasting impact in women with PPCM.
Methods and results
A nationwide Danish cohort of women with PPCM (PPCM group, n = 28), age matched women with previous preeclampsia (n = 28) and uncomplicated pregnancies (n = 28) participated in a follow-up study including biomarker analysis, exercise testing and cardiac magnetic resonance imaging. The median time to follow-up was 91 months (range 27-137 months) for the PPCM group. Levels of sFlt-1, placental growth factor, N-terminal pro-natriuretic brain peptide, and copeptin were all significantly higher in the PPCM group. More women in the PPCM group had detectable CD activity (68%) compared with the preeclampsia group (29%) and uncomplicated pregnancies group (36%) (P = .0002). Levels of angiogenic factors and biomarkers correlated inversely with maximal exercise capacity and cardiac functional parameters assessed with cardiac magnetic resonance imaging.
Conclusions
Women with PPCM had higher biomarker levels and CD activity up to 7 years after diagnosis. Higher biomarker levels correlated inversely with maximal exercise capacity and markers of cardiac dysfunction suggesting that persistent angiogenic imbalance and increased CD activity is associated with residual cardiac dysfunction.

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 30 Jan 2021; 27:168-175
Ersbøll AS, Goetze JP, Johansen M, Hauge MG, ... Gustafsson F, Damm P
J Card Fail: 30 Jan 2021; 27:168-175 | PMID: 33422687
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Abstract

Effects of Depression on Heart Failure Self-Care.

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

Copyright © 2020 Elsevier Inc. All rights reserved.

J Card Fail: 28 Jan 2021; epub ahead of print
Freedland KE, Skala JA, Steinmeyer BC, Carney RM, Rich MW
J Card Fail: 28 Jan 2021; epub ahead of print | PMID: 33358958
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Abstract

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

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

Copyright © 2021 Elsevier Inc. All rights reserved.

J Card Fail: 22 Jan 2021; epub ahead of print
Perez AL, Grodin JL, Chaikijurajai T, Wu Y, ... Starling RC, Tang WHW
J Card Fail: 22 Jan 2021; epub ahead of print | PMID: 33497809
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Abstract

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

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

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

J Card Fail: 22 Jan 2021; epub ahead of print
Markousis-Mavrogenis G, Tromp J, Mentz RJ, O'Connor CM, ... Voors AA, van der Meer P
J Card Fail: 22 Jan 2021; epub ahead of print | PMID: 33497808
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Abstract

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

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

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

J Card Fail: 22 Jan 2021; epub ahead of print
Jain P, Adji A, Emmanuel S, Robson D, ... Macdonald PS, Hayward CS
J Card Fail: 22 Jan 2021; epub ahead of print | PMID: 33497807
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Impact:

This program is still in alpha version.