Topic: Heart Failure

Abstract

A simplified wall-based model for regional innervation/perfusion mismatch assessed by cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT to predict arrhythmic events in ischaemic heart failure.

Verschure DO, Poel E, Travin MI, Henzlova MJ, ... Jacobson AF, Verberne HJ
Aims
Cardiac 123iodine-meta-iodobenzylguanidine (123I-mIBG) single-photon emission computed tomography (SPECT) imaging provides information on regional myocardial innervation. However, the value of the commonly used 17-segment summed defect score (SDS) as a prognostic marker is uncertain. The present study examined whether a simpler regional scoring approach for evaluation of 123I-mIBG SPECT combined with rest 99mTc-tetrofosmin SPECT myocardial perfusion imaging could improve prediction of arrhythmic events (AEs) in patients with ischaemic heart failure (HF).
Methods and results
Five hundred and two ischaemic HF subjects of the ADMIRE-HF study with complete cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT studies were included. Both SPECT image sets were read together by two experienced nuclear imagers and scored by consensus. In addition to standard 17-segment scoring, the readers classified walls (i.e. anterior, lateral, inferior, septum and apex) as normal, matched defect, mismatched (innervation defect > perfusion defect), or reverse mismatched (perfusion defect > innervation defect). Cox proportional hazards ratios (HRs) were used to determine if age, body mass index, functional class, left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP), norepinephrine, 123I-mIBG SDS, 99mTc-tetrofosmin SDS, innervation/perfusion mismatch SDS, and our simplified visual innervation/perfusion wall classification were associated with occurrence of AEs (i.e. sudden cardiac death, sustained ventricular tachycardia, resuscitated cardiac arrest, appropriate implantable cardioverter-defibrillator therapy). At 2-year median follow-up, 52 subjects (10.4%) had AEs. Subjects with 1 or 2 mismatched walls were twice as likely to have AEs compared with subjects with either 0 or 3-5 mismatched walls (16.3% vs. 8.3%, P = 0.010). Cox regression analyses showed that patients with a visual mismatch in 1-2 walls had an almost two times higher risk of AEs [HR 2.084 (1.109-3.914), P = 0.001]. None of the other innervation, perfusion and mismatch scores using standard 17 segments were associated with AEs. BNP (ng/L) was the only non-imaging parameter associated with AEs.
Conclusion
A visual left ventricular wall-level based scoring method identified highest AE risk in ischaemic HF subjects with intermediate levels of innervation/perfusion mismatches. This simple technique for the evaluation of SPECT studies, which are often challenging in HF subjects, seems to be superior to the 17-segment scoring method.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Imaging: 22 Aug 2022; 23:1201-1209
Verschure DO, Poel E, Travin MI, Henzlova MJ, ... Jacobson AF, Verberne HJ
Eur Heart J Cardiovasc Imaging: 22 Aug 2022; 23:1201-1209 | PMID: 34427293
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Abstract

Non-coding RNAs in cardiac inflammation: key drivers in the pathophysiology of heart failure.

Sansonetti M, De Windt LJ
Heart failure is among the most progressive diseases and a leading cause of morbidity. Despite several advances in cardiovascular therapies, pharmacological treatments are limited to relieve symptoms without curing cardiac injury. Multiple observations point to the involvement of immune cells as key drivers in the pathophysiology of heart failure. In particular, there is a growing recognition that heart failure is related to a prolonged and insufficiently repressed inflammatory response leading to molecular, cellular, and functional cardiac alterations. Over the last decades, non-coding RNAs are recognized as prominent mediators of cardiac inflammation, affecting the function of several immune cells. In the current review, we explore the contribution of the diverse immune cells in the progression of heart failure, revealing mechanistic functions for non-coding RNAs in cardiac immune cells as a new and exciting field of investigation.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Cardiovasc Res: 20 Jul 2022; 118:2058-2073
Sansonetti M, De Windt LJ
Cardiovasc Res: 20 Jul 2022; 118:2058-2073 | PMID: 34097013
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Abstract

Discovery of a first-in-class inhibitor of sulfide:quinone oxidoreductase that protects against adverse cardiac remodelling and heart failure.

Jackson MR, Cox KD, Baugh SDP, Wakeen L, ... Polyak B, Jorns MS
Aims
Hydrogen sulfide (H2S) is a potent signalling molecule that activates diverse cardioprotective pathways by post-translational modification (persulfidation) of cysteine residues in upstream protein targets. Heart failure patients with reduced ejection fraction (HFrEF) exhibit low levels of H2S. Sulfide:quinone oxidoreductase (SQOR) catalyses the first irreversible step in the metabolism of H2S and plays a key role in regulating H2S-mediated signalling. Here, the aim of this study was to discover a first-in-class inhibitor of human SQOR and evaluate its cardioprotective effect in an animal model of HFrEF.
Methods and results
We identified a potent inhibitor of human SQOR (STI1, IC50 = 29 nM) by high-throughput screening of a small-molecule library, followed by focused medicinal chemistry optimization and structure-based design. STI1 is a competitive inhibitor that binds with high selectivity to the coenzyme Q-binding pocket in SQOR. STI1 exhibited very low cytotoxicity and attenuated the hypertrophic response of neonatal rat ventricular cardiomyocytes and H9c2 cells induced by neurohormonal stressors. A mouse HFrEF model was produced by transverse aortic constriction (TAC). Treatment of TAC mice with STI1 mitigated the development of cardiomegaly, pulmonary congestion, dilatation of the left ventricle, and cardiac fibrosis and decreased the pressure gradient across the aortic constriction. Moreover, STI1 dramatically improved survival, preserved cardiac function, and prevented the progression to HFrEF by impeding the transition from compensated to decompensated left ventricle hypertrophy.
Conclusion
We demonstrate that the coenzyme Q-binding pocket in human SQOR is a druggable target and establish proof of concept for the potential of SQOR inhibitors to provide a novel therapeutic approach for the treatment of HFrEF.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Cardiovasc Res: 22 Jun 2022; 118:1771-1784
Jackson MR, Cox KD, Baugh SDP, Wakeen L, ... Polyak B, Jorns MS
Cardiovasc Res: 22 Jun 2022; 118:1771-1784 | PMID: 34132787
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Abstract

Weekend vs. weekday admission and clinical outcomes in heart failure patients with and without atrial fibrillation in Taiwan.

Hu WS, Lin CL
Aims
We conducted this study to explore the associations of weekend and weekday admission with the clinical events among heart failure (HF) patients with and without comorbid atrial fibrillation (AF).
Methods and results
In this study, we recruited 57 919 HF patients without AF hospitalized on weekends and 57 919 HF patients without AF hospitalized on weekdays. There were 21407 and 21407 HF patients with AF hospitalized on weekends and weekdays, respectively. The outcomes of interest included all-cause mortality, cardiovascular (CV) death, and HF recurrence requiring admission. The Cox proportional hazard regression model was applied to estimate the hazard ratio. Variables found to be statistically significant in a univariable Cox proportional hazard regression model were further examined in a multivariable Cox proportional hazard regression model. The cumulative incidence curves were obtained by the Kaplan-Meier method and assessed by the log-rank test. HF patients with AF and hospitalized on weekends had the highest incidence rates of rehospitalization due to HF (233.8 per 1000 person-years) and CV death (23.9 per 1000 person-years) among four groups. The Kaplan-Meier method shows that HF patients with AF had the higher cumulative incidence of rehospitalization due to HF than the patients without AF.
Conclusion
HF patients with AF and hospitalized on weekends are at highest risk of HF recurrence requiring hospitalization among these four groups.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Eur Heart J Cardiovasc Pharmacother: 08 Jun 2022; 8:346-352
Hu WS, Lin CL
Eur Heart J Cardiovasc Pharmacother: 08 Jun 2022; 8:346-352 | PMID: 34180528
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Abstract

Activity of the adrenomedullin system to personalise post-discharge diuretic treatment in acute heart failure.

Kozhuharov N, Ng L, Wussler D, Strebel I, ... Breidthardt T, Mueller C
Background
Quantifying the activity of the adrenomedullin system might help to monitor and guide treatment in acute heart failure (AHF) patients. The aims were to (1) identify AHF patients with marked benefit or harm from specific treatments at hospital discharge and (2) predict mortality by quantifying the adrenomedullin system activity.
Methods
This was a prospective multicentre study. AHF diagnosis and phenotype were centrally adjudicated by two independent cardiologists among patients presenting to the emergency department with acute dyspnoea. Adrenomedullin system activity was quantified using the biologically active component, bioactive adrenomedullin (bio-ADM), and a prohormone fragment, midregional proadrenomedullin (MR-proADM). Bio-ADM and MR-proADM concentrations were measured in a blinded fashion at presentation and at discharge. Interaction with specific treatments at discharge and the utility of these biomarkers on predicting outcomes during 365-day follow-up were assessed.
Results
Among 1886 patients with adjudicated AHF, 514 patients (27.3%) died during 365-day follow-up. After adjusting for age, creatinine, and treatment at discharge, patients with bio-ADM plasma concentrations above the median (> 44.6 pg/mL) derived disproportional benefit if treated with diuretics (interaction p values < 0.001). These findings were confirmed when quantifying adrenomedullin system activity using MR-proADM (n = 764) (interaction p values < 0.001). Patients with bio-ADM plasma concentrations above the median were at increased risk of death (hazard ratio 1.87, 95% CI 1.57-2.24; p < 0.001). For predicting 365-day all-cause mortality, both biomarkers performed well, with MR-proADM presenting an even higher predictive accuracy compared to bio-ADM (p < 0.001).
Conclusions
Quantifying the adrenomedullin\'s system activity may help to personalise post-discharge diuretic treatment and enable accurate risk-prediction in AHF.

© 2021. The Author(s).

Clin Res Cardiol: 01 Jun 2022; 111:627-637
Kozhuharov N, Ng L, Wussler D, Strebel I, ... Breidthardt T, Mueller C
Clin Res Cardiol: 01 Jun 2022; 111:627-637 | PMID: 34302189
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Abstract

Epidemiological and clinical boundaries of heart failure with preserved ejection fraction.

Gentile F, Ghionzoli N, Borrelli C, Vergaro G, ... Passino C, Giannoni A
Heart failure with preserved ejection fraction (HFpEF) is highly prevalent and is associated with relevant morbidity and mortality. However, an evidence-based treatment is still absent. The heterogeneous definitions, differences in aetiology/pathophysiology, and diagnostic challenges of HFpEF made it difficult to define its epidemiological landmarks so far. Several large registries and observational studies have recently disclosed an increasing incidence/prevalence, as well as its prognostic significance. An accurate definition of HFpEF epidemiological boundaries and phenotypes is mandatory to develop novel effective and rational therapeutic approaches.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Eur J Prev Cardiol: 27 May 2022; 29:1233-1243
Gentile F, Ghionzoli N, Borrelli C, Vergaro G, ... Passino C, Giannoni A
Eur J Prev Cardiol: 27 May 2022; 29:1233-1243 | PMID: 33963839
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Abstract

Natural history and prognostic significance of iron deficiency and anaemia in ambulatory patients with chronic heart failure.

Graham FJ, Masini G, Pellicori P, Cleland JGF, ... Kazmi S, Clark AL
Aims
Iron deficiency (ID) and anaemia are common in heart failure; less is known about changes over time.
Methods and results
We investigated prevalence, incidence and resolution of ID and anaemia in 906 patients with chronic heart failure (median age 73 (65-79) years, 70% men, 51% with heart failure with reduced ejection fraction) 1 year apart. ID was defined as serum iron ≤13 µmol/L and anaemia as haemoglobin <13.0 g/dL for men or <12.0 g/dL for women. FAIR-HF criteria for ID were also considered. At baseline, 10% had anaemia without ID, 23% had ID without anaemia, 20% had both, and 47% had neither. Percentages changed little over 1 year, but 157 (30%) patients had new-onset ID, 104 (16%) new-onset anaemia, whilst ID resolved in 173 (44%) and anaemia in 63 (23%). Compared to those who remained iron replete (iron >13 µmol/L), mortality was higher in those with persistent or incident ID at 1 year [hazard ratio (HR) 1.81 (1.23-2.67), and HR 1.40 (0.91-2.14), respectively] in multivariable models (P = 0.02). Compared to persistent ID, resolution of ID was associated with a lower mortality [HR 0.61 (0.44-0.86); P = 0.004]. Changes in ID defined by FAIR-HF criteria were not similarly associated with mortality. Anaemia was associated with a poor outcome even if it resolved.
Conclusions
The prevalence and incidence of ID and anaemia are high in chronic heart failure but so is the rate of resolution. Persistent or incident ID, defined by a serum iron ≤13 µmol/L, is associated with higher mortality and resolution of ID with lower mortality.

© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Eur J Heart Fail: 01 May 2022; 24:807-817
Graham FJ, Masini G, Pellicori P, Cleland JGF, ... Kazmi S, Clark AL
Eur J Heart Fail: 01 May 2022; 24:807-817 | PMID: 34050582
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Abstract

Serum sodium and eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.

Martens P, Ferreira JP, Vincent J, Abreu P, ... Zannad F, Rossignol P
Background
Sodium changes are common in myocardial infarction (MI) complicated with left ventricular systolic dysfunction (LVSD) and/or heart failure (HF). Sodium handling is fine-tuned in the distal nephron, were eplerenone exhibits some of its pleotropic effects. Little is known about the effect of eplerenone on serum sodium and the prognostic relevance of sodium alterations in patients with MI complicated with LVSD and/or HF.
Methods
The EPHESUS trial randomized 6632 patients to either eplerenone or placebo. Hyponatremia and hypernatremia were defined as sodium < 135 mmol/L or > 145 mmol/L, respectively. Linear mixed models and time updated Cox regression analysis were used to determine the effect of eplerenone on sodium changes and the prognostic importance of sodium changes, respectively. The primary outcomes were all-cause mortality and a composite of cardiovascular (CV) mortality and CV-hospitalization.
Results
A total of 6221 patients had a post-baseline sodium measurement, 797 patients developed hyponatremia (mean of 0.2 events/per patient) and 1476 developed hypernatremia (mean of 0.4 events/per patient). Patients assigned to eplerenone had a lower mean serum sodium over the follow-up (140 vs 141 mmol/L; p < 0.0001) and more often developed hyponatremia episodes (15 vs 11% p = 0.0001) and less often hypernatremia episodes (22 vs. 26% p = 0.0003). Hyponatremia, but not hypernatremia was associated with adverse outcome for all outcome endpoints in the placebo group but not in the eplerenone group (interaction p value < 0.05 for all). Baseline sodium values did not influence the treatment effect of eplerenone in reducing the various endpoints (interaction p value > 0.05 for all). Development of new-onset hyponatremia following eplerenone initiation did not diminish the beneficial eplerenone treatment effect.
Conclusion
Eplerenone induces minor reductions in serum sodium. The beneficial effect of eplerenone was maintained regardless of the baseline serum sodium or the development of hyponatremia. Sodium alterations should not refrain clinicians from prescribing eplerenone to patients who had an MI complicated with LVSD and/or HF.
Trail registry
ClinicalTrials.gov identifier: NCT00232180. Serum sodium and eplerenone use in patients with a myocardial infarction and left ventricular dysfunction or heart failure: insights from the EPHESUS trial.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 01 Apr 2022; 111:380-392
Martens P, Ferreira JP, Vincent J, Abreu P, ... Zannad F, Rossignol P
Clin Res Cardiol: 01 Apr 2022; 111:380-392 | PMID: 33893561
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Abstract

Exercise hemodynamics in heart failure patients with preserved and mid-range ejection fraction: key role of the right heart.

Rieth AJ, Richter MJ, Tello K, Gall H, ... Schulze PC, Hamm CW
Objective
We sought to explore whether classification of patients with heart failure and mid-range (HFmrEF) or preserved ejection fraction (HFpEF) according to their left ventricular ejection fraction (LVEF) identifies differences in their exercise hemodynamic profile, and whether classification according to an index of right ventricular (RV) function improves differentiation.
Background
Patients with HFmrEF and HFpEF have hemodynamic compromise on exertion. The classification according to LVEF implies a key role of the left ventricle. However, RV involvement in exercise limitation is increasingly recognized. The tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure (TAPSE/PASP) ratio is an index of RV and pulmonary vascular function. Whether exercise hemodynamics differ more between HFmrEF and HFpEF than between TAPSE/PASP tertiles is unknown.
Methods
We analyzed 166 patients with HFpEF (LVEF ≥ 50%) or HFmrEF (LVEF 40-49%) who underwent basic diagnostics (laboratory testing, echocardiography at rest, and cardiopulmonary exercise testing [CPET]) and exercise with right heart catheterization. Hemodynamics were compared according to echocardiographic left ventricular or RV function.
Results
Exercise hemodynamics (e.g. pulmonary arterial wedge pressure/cardiac output [CO] slope, CO increase during exercise, and maximum total pulmonary resistance) showed no difference between HFpEF and HFmrEF, but significantly differed across TAPSE/PASP tertiles and were associated with CPET results. N-terminal pro-brain natriuretic peptide concentration also differed significantly across TAPSE/PASP tertiles but not between HFpEF and HFmrEF.
Conclusion
In patients with HFpEF or HFmrEF, TAPSE/PASP emerged as a more appropriate stratification parameter than LVEF to predict clinically relevant impairment of exercise hemodynamics. Stratification of exercise hemodynamics in patients with HFpEF or HFmrEF according to LVEF or TAPSE/PASP, showing significant distinctions only with the RV-based strategy. All data are shown as median [upper limit of interquartile range] and were calculated using the independent-samples Mann-Whitney U test or Kruskal-Wallis test. PVR pulmonary vascular resistance; max maximum level during exercise.

© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.

Clin Res Cardiol: 01 Apr 2022; 111:393-405
Rieth AJ, Richter MJ, Tello K, Gall H, ... Schulze PC, Hamm CW
Clin Res Cardiol: 01 Apr 2022; 111:393-405 | PMID: 34110459
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Abstract

Establishing a cardiac training group for patients with heart failure: the \"HIP-in-Würzburg\" study.

Güder G, Wilkesmann J, Scholz N, Leppich R, ... Breunig M, Störk S
Background
Exercise training in heart failure (HF) is recommended but not routinely offered, because of logistic and safety-related reasons. In 2020, the German Society for Prevention&Rehabilitation and the German Society for Cardiology requested establishing dedicated \"HF training groups.\" Here, we aimed to implement and evaluate the feasibility and safety of one of the first HF training groups in Germany.
Methods
Twelve patients (three women) with symptomatic HF (NYHA class II/III) and an ejection fraction ≤ 45% participated and were offered weekly, physician-supervised exercise training for 1 year. Patients received a wrist-worn pedometer (M430 Polar) and underwent the following assessments at baseline and after 4, 8 and 12 months: cardiopulmonary exercise test, 6-min walk test, echocardiography (blinded reading), and quality of life assessment (Kansas City Cardiomyopathy Questionnaire, KCCQ).
Results
All patients (median age [quartiles] 64 [49; 64] years) completed the study and participated in 76% of the offered 36 training sessions. The pedometer was worn ≥ 1000 min per day over 86% of the time. No cardiovascular events occurred during training. Across 12 months, NT-proBNP dropped from 986 pg/ml [455; 1937] to 483 pg/ml [247; 2322], and LVEF increased from 36% [29;41] to 41% [32;46]%, (p for trend = 0.01). We observed no changes in exercise capacity except for a subtle increase in peak VO2% predicted, from 66.5 [49; 77] to 67 [52; 78]; p for trend = 0.03. The physical function and social limitation domains of the KCCQ improved from 60 [54; 82] to 71 [58; 95, and from 63 [39; 83] to 78 [64; 92]; p for trend = 0.04 and = 0.01, respectively. Positive trends were further seen for the clinical and overall summary scores.
Conclusion
This pilot study showed that the implementation of a supervised HF-exercise program is feasible, safe, and has the potential to improve both quality of life and surrogate markers of HF severity. This first exercise experiment should facilitate the design of risk-adopted training programs for patients with HF.

© 2021. The Author(s).

Clin Res Cardiol: 01 Apr 2022; 111:406-415
Güder G, Wilkesmann J, Scholz N, Leppich R, ... Breunig M, Störk S
Clin Res Cardiol: 01 Apr 2022; 111:406-415 | PMID: 34159415
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Abstract

Rationale and design of the EPCHF trial: the early palliative care in heart failure trial (EPCHF).

Becher MU, Balata M, Hesse M, Draht F, ... Radbruch L, Nickenig G
The progressive nature of heart failure (HF) coupled with high mortality and poor quality-of-life (QoL) mandates greater attention to palliative care (PC) as a routine component of HF management. Limited evidence exists from randomized controlled trials supporting the use of interdisciplinary palliative care in the progressive course of HF. The early palliative care in heart failure trial (EPCHF) is a prospective, controlled, nonblinded, multicenter study of an interdisciplinary palliative care intervention in 200 patients with symptomatic HF characterized by NYHA ≥ 2. The 12-month EPCHF intervention includes monthly consultations by a palliative care team focusing on physical and psychosocial symptom relief, attention to spiritual concerns and advance care planning. The primary endpoint is evaluated by health-related QoL questionnaires after 12 months of treatment. First the functional assessment of chronic illness therapy palliative care (FACIT-Pal) score evaluating QoL living with a chronic disease and second the Kansas City cardiomyopathy questionnaire (KCCQ) measuring QoL living with heart failure will be determined. Secondary endpoints are changes in anxiety/depression (HADS), symptom burden score (MIDOS), spiritual well-being functional assessment of chronic illness therapy spiritual well-being scale (FACIT-Sp), medical resource and cost assessment. EPCHF will help evaluate the efficacy and cost-effectiveness of palliative care in symptomatic HF using a patient-centered outcome as well as clinical and economic endpoints. EPCHF is funded by the Bundesministerium für Bildung und Forschung (BMBF, 01GY17).

© 2021. The Author(s).

Clin Res Cardiol: 01 Apr 2022; 111:359-367
Becher MU, Balata M, Hesse M, Draht F, ... Radbruch L, Nickenig G
Clin Res Cardiol: 01 Apr 2022; 111:359-367 | PMID: 34241674
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Abstract

Diastolic dysfunction in individuals with and without heart failure with preserved ejection fraction.

Wenzel JP, Kellen RB, Magnussen C, Blankenberg S, ... Schnabel R, Nikorowitsch J
Aim
Left ventricular diastolic dysfunction (DD), a common finding in the general population, is considered to be associated with heart failure with preserved ejection faction (HFpEF). Here we evaluate the prevalence and correlates of DD in subjects with and without HFpEF in a middle-aged sample of the general population.
Methods and results
From the first 10,000 participants of the population-based Hamburg City Health Study (HCHS), 5913 subjects (mean age 64.4 ± 8.3 years, 51.3% females), qualified for the current analysis. Diastolic dysfunction (DD) was identified in 753 (12.7%) participants. Of those, 11.2% showed DD without HFpEF (ALVDD) while 1.3% suffered from DD with HFpEF (DDwHFpEF). In multivariable regression analysis adjusted for major cardiovascular risk factors, ALVDD was associated with arterial hypertension (OR 2.0, p < 0.001) and HbA1c (OR 1.2, p = 0.007). Associations of both ALVDD and DDwHFpEF were: age (OR 1.7, p < 0.001; OR 2.7, p < 0.001), BMI (OR 1.2, p < 0.001; OR 1.6, p = 0.001), and left ventricular mass index (LVMI). In contrast, female sex (OR 2.5, p = 0.006), atrial fibrillation (OR 2.6, p = 0.024), CAD (OR 7.2, p < 0.001) COPD (OR 3.9, p < 0.001), and QRS duration (OR 1.4, p = 0.005) were strongly associated with DDwHFpEF but not with ALVDD.
Conclusion
The prevalence of DD in a sample from the first 10,000 participants of the population-based HCHS was 12.7% of whom 1.3% suffered from HFpEF. DD with and without HFpEF showed significant associations with different major cardiovascular risk factors and comorbidities warranting further research for their possible role in the formation of both ALVDD and DDwHFpEF.

© 2021. The Author(s).

Clin Res Cardiol: 01 Apr 2022; 111:416-427
Wenzel JP, Kellen RB, Magnussen C, Blankenberg S, ... Schnabel R, Nikorowitsch J
Clin Res Cardiol: 01 Apr 2022; 111:416-427 | PMID: 34269862
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Abstract

Influence of receptor selectivity on benefits from SGLT2 inhibitors in patients with heart failure: a systematic review and head-to-head comparative efficacy network meta-analysis.

Täger T, Frankenstein L, Atar D, Agewall S, ... Cleland JGF, Fröhlich H
Background
Receptor selectivity of sodium-glucose cotransporter-2 inhibitors (SGLT2i) varies greatly between agents. The overall improvement of cardiovascular (CV) outcomes in heart failure (HF) patients varies between trials. We, therefore, evaluated the comparative efficacy of individual SGLT2i and the influence of their respective receptor selectivity thereon.
Methods
We identified randomized controlled trials investigating the use of SGLT2i in patients with HF-either as the target cohort or as a subgroup of it. Comparators included placebo or any other active treatment. The primary endpoint was the composite of hospitalization for HF or CV death. Secondary outcomes included all-cause mortality, CV mortality, hospitalization for HF, worsening renal function (RF), and the composite of worsening RF or CV death. Evidence was synthesized using network meta-analysis. In addition, the impact of receptor selectivity on outcomes was analysed using meta-regression.
Results
We identified 18,265 patients included in 22 trials. Compared to placebo, selective and non-selective SGLT2i improved fatal and non-fatal HF events. Head-to-head comparisons suggest superior efficacy with sotagliflozin as compared to dapagliflozin, empagliflozin or ertugliflozin. No significant difference was found between canagliflozin and sotagliflozin. Meta-regression analyses show a decreasing benefit on HF events with increasing receptor selectivity of SGLT2i. In contrast, receptor selectivity did not affect mortality and renal endpoints and no significant difference between individual SGLT2i was noted.
Conclusion
Our data point towards a class-effect of SGLT2i on mortality and renal outcomes. However, non-selective SGLT2i such as sotagliflozin may be superior to highly selective SGLT2i in terms of HF outcomes.

© 2021. The Author(s).

Clin Res Cardiol: 01 Apr 2022; 111:428-439
Täger T, Frankenstein L, Atar D, Agewall S, ... Cleland JGF, Fröhlich H
Clin Res Cardiol: 01 Apr 2022; 111:428-439 | PMID: 34498169
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Abstract

Validation of Heart Failure-Specific Risk Equations in 1.3 Million Israeli Adults and Usefulness of Combining Ambulatory and Hospitalization Data from a Large Integrated Health Care Organization.

Khan SS, Barda N, Greenland P, Dagan N, ... Balicer R, Rasmussen-Torvik LJ
Heart failure (HF) prevalence is increasing worldwide and is associated with significant morbidity and mortality. Guidelines emphasize prevention in those at-risk, but HF-specific risk prediction equations developed in United States population-based cohorts lack external validation in large, real-world datasets outside of the United States. The purpose of this study was to assess the model performance of the pooled cohort equations to prevent HF (PCP-HF) within a contemporary electronic health record for 5- and 10-year risk. Using a retrospective cohort study design of Israeli residents between 2008 and 2018 with continuous membership until end of follow-up, HF, or death, we quantified 5- and 10-year estimated risks of HF using the PCP-HF equations, which integrate demographics (age, gender, and race) and risk factors (body mass index, systolic blood pressure, glucose, medication use for hypertension or diabetes, and smoking status). Of 1,394,411 patients included, 56% were women with mean age of 49.6 (SD 13.2) years. Incident HF occurred in 1.2% and 4.5% of participants over 5 and 10 years of follow-up. The PCP-HF model had excellent discrimination for 5- and 10-year predictions of incident HF (C Statistic 0.82 [0.82 to 0.82] and 0.84 [0.84 to 0.84]), respectively. In conclusion, HF-specific risk equations (PCP-HF) accurately predict the risk of incident HF in ambulatory and hospitalized patients using routinely available clinical data.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 01 Apr 2022; 168:105-109
Khan SS, Barda N, Greenland P, Dagan N, ... Balicer R, Rasmussen-Torvik LJ
Am J Cardiol: 01 Apr 2022; 168:105-109 | PMID: 35031113
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Abstract

Relation of Cigarette Smoking and Heart Failure in Adults ≥65 Years of Age (From the Cardiovascular Health Study).

Gottdiener JS, Buzkova P, Kahn PA, DeFilippi C, ... Psaty B, Gardin JM
Cigarette smoking is associated with adverse cardiac outcomes, including incident heart failure (HF). However, key components of potential pathways from smoking to HF have not been evaluated in older adults. In a community-based study, we studied cross-sectional associations of smoking with blood and imaging biomarkers reflecting mechanisms of cardiac disease. Serial nested, multivariable Cox models were used to determine associations of smoking with HF, and to assess the influence of biochemical and functional (cardiac strain) phenotypes on these associations. Compared with never smokers, smokers had higher levels of inflammation (C-reactive protein and interleukin-6), cardiomyocyte injury (cardiac troponin T [hscTnT]), myocardial \"stress\"/fibrosis (soluble suppression of tumorigenicity 2 [sST2], galectin 3), and worse left ventricle systolic and diastolic function. In models adjusting for age, gender, and race (DEMO) and for clinical factors potentially in the causal pathway (CLIN), smoking exposures were associated with C-reactive protein and interleukin-6, sST2, hscTnT, and with N-terminal pro-brain natriuretic protein (in Whites). In DEMO adjusted models, the cumulative burden of smoking was associated with worse left ventricle systolic strain. Current smoking and former smoking were associated with HF in DEMO models (hazard ratio 1.41, 95% confidence interval 1.22 to 1.64 and hazard ratio 1.14, 95% confidence interval 1.03 to 1.25, respectively), and with current smoking after CLIN adjustment. Adjustment for time-varying myocardial infarction, inflammation, cardiac strain, hscTnT, sST2, and galectin 3 did not materially alter the associations. Smoking was associated with HF with preserved and decreased ejection fraction. In conclusion, in older adults, smoking is associated with multiple blood and imaging biomarker measures of pathophysiology previously linked to HF, and to incident HF even after adjustment for clinical intermediates.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 01 Apr 2022; 168:90-98
Gottdiener JS, Buzkova P, Kahn PA, DeFilippi C, ... Psaty B, Gardin JM
Am J Cardiol: 01 Apr 2022; 168:90-98 | PMID: 35045935
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Abstract

Relation of Cardiorenal Syndrome to Mitral and Tricuspid Regurgitation in Acute Decompensated Heart Failure.

Seghatol FF, Martin KD, Haj-Asaad A, Xie M, Prabhu SD
This study aimed to investigate the role of secondary mitral regurgitation (MR) and tricuspid regurgitation (TR) in the pathogenesis of cardiorenal syndrome (CRS). Worsening renal function in patients with acute decompensated heart failure receiving diuretic therapy is defined as CRS and is related to central venous congestion. The role of secondary MR and TR is not well studied. We retrospectively reviewed the electronic medical records of 80 consecutive patients hospitalized with acute decompensated heart failure. Patients were divided into 2 groups: group 1 (CRS) if creatinine increased >0.3 mg/dl from baseline and group 2 (no CRS) if creatinine remained stable or improved with diuretic therapy. Admission creatinine was higher in group 1 compared with group 2 (1.5 vs 1.2 mg/dl, p = 0.033). The magnitude of MR and TR were higher by both visual assessment (moderate to severe [3+] or severe [4+] MR in 68% of patients in group 1 vs 3% in group 2, p <0.0001; 3+ or 4+ TR in 48% of patients in group 1 vs 10% in group 2, p = 0.0004) and by vena contracta (MR 0.6 ± 0.2 cm in group 1 vs 0.4 ± 0.1 cm in group 2, p <0.0001; TR 0.5 ± 0.2 cm in group 1 vs 0.4 ± 0.2 cm in group 2, p = 0.0013). By using receiver operating characteristic curves, MR and TR were the most sensitive parameters in predicting CRS. In conclusion, renal function on admission and moderate to severe or severe MR and TR are highly predictive of the risk of developing CRS.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 31 Mar 2022; 168:99-104
Seghatol FF, Martin KD, Haj-Asaad A, Xie M, Prabhu SD
Am J Cardiol: 31 Mar 2022; 168:99-104 | PMID: 35045927
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Abstract

Association of improvement in functional capacity after rehabilitation with long-term survival in heart failure.

Scrutinio D, Guida P, Passantino A, Scalvini S, ... Vaninetti R, La Rovere MT
Background
The prognostic value of change in six-minute walking distance (6MWD) after treatment to predict mortality in heart failure (HF) remains a controversial issue. We assessed the prognostic value of rehabilitation-induced improvement in 6MWD in predicting mortality in patients with HF.
Methods
We studied 2257 patients admitted to six inpatient rehabilitation facilities after a hospitalization for HF (N. 912) or because of worsening functional capacity and/or deteriorating clinical status (N. 1345). A six-minute walking test was performed at admission and discharge. The primary outcome was 3-year all-cause mortality after discharge from cardiac rehabilitation. We used multivariable Cox proportional hazard modeling to assess the association of increase in 6MWD with 3-year mortality, adjusting for established predictors of mortality.
Results
6MWD significantly increased by 61 m (p < .001) from admission to discharge and 969 patients (42.9%) achieved an increase in 6MWD >50 m. After full adjustment, an increase in 6MWD >50 m was associated with a 22% decreased risk for 3-year mortality (HR 0.78 [95% CI 0.68-0.91]; p = .002). When modeled as a continuous variable, improvement in 6MWD remained independently associated with decreased risk for 3-year mortality (HR per each 50 m increase: 0.92 [95% CI 0.88-0.96]).
Conclusions
Rehabilitation-induced improvement in 6MWD was associated with a significantly reduced risk for 3-year mortality. Our data also suggest that an improvement in 6MWD of more than 50 m could represent a clinically meaningful endpoint of cardiac rehabilitation for patients with heart failure.

Copyright © 2022 Elsevier B.V. All rights reserved.

Int J Cardiol: 31 Mar 2022; 352:92-97
Scrutinio D, Guida P, Passantino A, Scalvini S, ... Vaninetti R, La Rovere MT
Int J Cardiol: 31 Mar 2022; 352:92-97 | PMID: 35074489
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Abstract

Lead With the Why: Research Recruitment of Older Adults With HF During COVID-19.

Degroot L
Recruitment of older adults with advanced heart failure is notoriously challenging, particularly for doctoral students conducting dissertation research studies with limited financial and personnel resources. Successful recruitment of participants requires a multifaceted recruitment strategy that is mindful of context and sensitive to the clinical partners who provide care in the recruitment setting. This article reflects on these challenges and proposes a practical framework to guide recruitment strategies in future research.

Copyright © 2022 Elsevier Inc. All rights reserved.

J Card Fail: 31 Mar 2022; 28:684-687
Degroot L
J Card Fail: 31 Mar 2022; 28:684-687 | PMID: 35121149
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Abstract

Association of readmission penalty amount with subsequent 30-day risk standardized readmission and mortality rates among patients hospitalized with heart failure: An analysis of get with the guidelines - heart failure participating centers.

Patel KV, Keshvani N, Pandey A, Vaduganathan M, ... Yancy CW, Fonarow GC
Background
The Hospital Readmissions Reduction Program penalizes hospitals with excess 30-day risk-standardized readmission rates (RSRR) for heart failure (HF). The association of financial penalty amount with subsequent short-term clinical outcomes is unknown.
Methods
Patients admitted to American Heart Association Get With The Guidelines-HF registry participating centers from October 1, 2012 through December 1, 2015 who had Medicare-linked data were included. October 2012 hospital-specific penalty amounts were calculated based on diagnosis-related group payments and excess readmission ratios. Adjusted Cox models were created to evaluate the association of penalty amount categories (non-penalized: 0%; low-penalized: >0%-<0.50%; mid-penalized ≥0.50%-<0.99%; high-penalized ≥0.99%) with subsequent 30-day RSRR and risk-standardized mortality rates (RSMR). Trends in post-discharge 30-day RSRR and RSMR from 2012 to 2015 were analyzed across hospitals stratified by penalty amount categories.
Results
The present study included 61,329 patients who were admitted across 262 hospitals. Compared with patients admitted to non-penalized hospitals (36.3%), those admitted to increasingly penalized hospitals were more likely to have higher 30-day RSRR (low-penalized [43.9%]: HR, 1.10 [95% CI, 1.04-1.16]; mid-penalized [12.0%]: HR, 1.07 [95% CI, 0.99-1.16]; high-penalized [7.9%]: HR, 1.23 [95% CI, 1.12-1.35]) but not 30-day RSMR. Over time, 30-day RSRR and RSMR did not meaningfully change across penalized versus non-penalized hospitals.
Conclusions
Financial penalties based on 30-day RSRR are not associated with declines in 30-day RSRR or RSMR from 2012 to 2015 among patients hospitalized with HF. Financially penalizing hospitals based on current Hospital Readmissions Reduction Program metrics may not incentivize improvements in short-term clinical outcomes for HF.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 30 Mar 2022; 246:1-11
Patel KV, Keshvani N, Pandey A, Vaduganathan M, ... Yancy CW, Fonarow GC
Am Heart J: 30 Mar 2022; 246:1-11 | PMID: 34973189
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Abstract

Ketone therapy for heart failure: current evidence for clinical use.

Takahara S, Soni S, Maayah ZH, Ferdaoussi M, Dyck JRB
During conditions that result in depleted circulating glucose levels, ketone bodies synthesized in the liver are necessary fuel substrates for the brain. In other organs, such as the heart, the reliance on ketones for generating energy in the absence of glucose is less important as the heart can utilize alternative fuel sources, such as fatty acids. However, during pathophysiological conditions, such as heart failure, cardiac defects in metabolic processes that normally allow for sufficient energy production from fatty acids and carbohydrates contribute to a decline in contractile function. As such, it has been proposed that the failing heart relies more on ketone bodies as an energy source than previously appreciated. Furthermore, it has been shown that ketone bodies function as signaling molecules that can suppress systemic and cardiac inflammation. Thus, it is possible that intentionally elevating circulating ketones may be beneficial as an adjunct treatment for heart failure. Although many approaches can be used for \'ketone therapy\', each of these has their own advantages and disadvantages in the treatment of heart failure. Thus, we summarize current preclinical and clinical studies involving various types of ketone therapy in cardiac disease and discuss the advantages and disadvantages of each modality as possible treatments for heart failure.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

Cardiovasc Res: 15 Mar 2022; 118:977-987
Takahara S, Soni S, Maayah ZH, Ferdaoussi M, Dyck JRB
Cardiovasc Res: 15 Mar 2022; 118:977-987 | PMID: 33705533
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Abstract

Clinical impact of changes in mitral regurgitation severity after medical therapy optimization in heart failure.

Pagnesi M, Adamo M, Sama IE, Anker SD, ... Voors AA, Metra M
Background
Few data are available regarding changes in mitral regurgitation (MR) severity with guideline-recommended medical therapy (GRMT) in heart failure (HF). Our aim was to evaluate the evolution and impact of MR after GRMT in the Biology study to Tailored treatment in chronic heart failure (BIOSTAT-CHF).
Methods
A retrospective post-hoc analysis was performed on HF patients from BIOSTAT-CHF with available data on MR status at baseline and at 9-month follow-up after GRMT optimization. The primary endpoint was a composite of all-cause death or HF hospitalization.
Results
Among 1022 patients with data at both time-points, 462 (45.2%) had moderate-severe MR at baseline and 360 (35.2%) had it at 9-month follow-up. Regression of moderate-severe MR from baseline to 9 months occurred in 192/462 patients (41.6%) and worsening from baseline to moderate-severe MR at 9 months occurred in 90/560 patients (16.1%). The presence of moderate-severe MR at 9 months, independent from baseline severity, was associated with an increased risk of the primary endpoint (unadjusted hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.57-2.63; p < 0.001), also after adjusting for the BIOSTAT-CHF risk-prediction model (adjusted HR, 1.85; 95% CI 1.43-2.39; p < 0.001). Younger age, LVEF ≥ 50% and treatment with higher ACEi/ARB doses were associated with a lower likelihood of persistence of moderate-severe MR at 9 months, whereas older age was the only predictor of worsening MR.
Conclusions
Among patients with HF undergoing GRMT optimization, ACEi/ARB up-titration and HFpEF were associated with MR improvement, and the presence of moderate-severe MR after GRMT was associated with worse outcome.

© 2022. The Author(s).

Clin Res Cardiol: 15 Mar 2022; epub ahead of print
Pagnesi M, Adamo M, Sama IE, Anker SD, ... Voors AA, Metra M
Clin Res Cardiol: 15 Mar 2022; epub ahead of print | PMID: 35294624
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Abstract

SGLT-2 inhibitors for treatment of heart failure in patients with and without type 2 diabetes: A practical approach for routine clinical practice.

Giaccari A, Pontremoli R, Perrone Filardi P
Sodium-glucose cotransporter-2 inhibitors (SGLT-2i), initially studied and approved for the treatment of diabetes, are now becoming a promising class of agents to treat heart failure (HF) and chronic kidney disease (CKD), even in patients without diabetes. While the potential benefits in several diseases (usually treated by different medical specialties) is amplifying the interest in these drugs, their use in frail patients with multiple pathologies and on polypharmacy can be complex, requiring a composite multidisciplinary approach. Following a brief overview of the evidence supporting the benefits of SGLT-2i in patients with HF or CKD, we herein provide guidance for prescribing SGLT-2i in daily practice using a multidisciplinary approach. A shared treatment algorithm is presented for initiating an SGLT-2i in patients already being treated for diabetes and HF. Tools to prevent hypoglycemia, blood pressure drop, genital infections, euglycemic diabetic ketoacidosis and eGFR dip are also provided. It is hoped that this practical, multidisciplinary guidance for initiating SGLT-2i in patients with HF and/or CKD, whatever therapy they are currently on, can help to offer SGLT-2i to the largest population of patients possible to provide the most therapeutic benefit.

Copyright © 2021. Published by Elsevier B.V.

Int J Cardiol: 14 Mar 2022; 351:66-70
Giaccari A, Pontremoli R, Perrone Filardi P
Int J Cardiol: 14 Mar 2022; 351:66-70 | PMID: 34979145
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Abstract

Inflammatory Markers and Risk of Heart Failure With Reduced to Preserved Ejection Fraction.

Albar Z, Albakri M, Hajjari J, Karnib M, Janus SE, Al-Kindi SG
Chronic systemic inflammation is associated with an increased risk of heart failure (HF). We sought to determine the association between biomarkers of systemic inflammation interleukin (IL)-6, IL-2, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) with those of HF and its subtypes. We hypothesize that inflammatory biomarkers IL-6, IL-2, TNF-α, and CRP are associated with HF and its subtypes. We included participants from the Multi-Ethnic Study of Atherosclerosis (a prospective population-based cohort study [2000 to 2002]), without a history of HF, and with available baseline inflammatory biomarkers. We explored the association of IL-6, IL-2, TNF-α, and CRP with incident HF, HF with reduced ejection fraction (left ventricular ejection fraction [LVEF] <40%, HFrEF), HF with midrange EF (LVEF 40% to 50%, HFmrEF), and HF with preserved ejection fraction (LVEF >50%, HFpEF). Among 6,814 participants, 195 developed HF over 10.9 years (56 HFrEF, 30 HFmrEF, and 57 HFpEF). In the models adjusted for clinical risk factors of HF, IL-6 (hazard ratio [HR] 1.33 per doubling; 95% confidence interval [CI] 1.10 to 1.60), TNF-α (HR 2.49 per doubling; 95% CI 1.18 to 5.28), and CRP (HR 1.18 per doubling; 95% CI 1.06 to 1.30) were associated with all HF, and IL-6 (HR 1.51 per doubling; 95% CI 1.09 to 2.10) and CRP (HR 1.21 per doubling; 95% CI: 1.01 to 1.45) were associated with incident HFpEF, whereas none of the examined biomarkers were associated with HFmrEF or HFrEF. In conclusion, inflammatory biomarkers (IL-6, TNF-α, and CRP) are independently associated with incident HF. IL-6 and CRP are associated with incident HFpEF but not HFrEF or HFmrEF. These findings suggest that activation of the IL-6/CRP pathway (as cause, consequence, or epiphenomenon) may be unique to HFpEF.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Mar 2022; 167:68-75
Albar Z, Albakri M, Hajjari J, Karnib M, Janus SE, Al-Kindi SG
Am J Cardiol: 14 Mar 2022; 167:68-75 | PMID: 34986991
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Abstract

Long-Term Risk of Heart Failure-Related Death and Heart Transplant After Congenital Heart Surgery in Childhood (from the Pediatric Cardiac Care Consortium).

Wright LK, Zmora R, Huang Y, Oster ME, ... Kochilas L, Kalogeropoulos A
We aimed to describe the longitudinal risk of advanced heart failure (HF) leading to death, heart transplantation, or ventricular assist device (VAD) placement after congenital heart surgery (CHS) and how it varies across the spectrum of congenital heart disease. We linked the records of patients who underwent first CHS in the Pediatric Cardiac Care Consortium between 1982 and 2003 with the United States National Death Index and Organ Procurement and Transplantation Network databases. Primary outcome was time from CHS discharge to HF-related death, heart transplant, or VAD placement, analyzed with proportional hazards models accounting for competing mortality. In 35,610 patients who survived a first CHS, there were 799 HF deaths, transplants, or VADs over a median of 23 years (interquartile range, 19 to 27). Cumulative incidence at 25 years was 2.3% (95% confidence interval [CI] 2.1% to 2.4%). Compared to mild 2-ventricle defects, the adjusted subhazard ratio for moderate and severe 2-ventricle defects was 3.21 (95% CI 2.28 to 4.52) and 9.46 (95% CI 6.71 to 13.3), respectively, and for single-ventricle defects 31.8 (95% CI 22.2 to 45.6). Systemic right ventricle carried the highest risk 2 years after CHS (subhazard ratio 2.76 [95% CI 2.08 to 3.68]). All groups had higher rates of HF-related death compared with the general population (cause-specific standardized mortality ratio 56.1 [95% CI 51.0 to 61.2]). In conclusion, the risk of advanced HF leading to death, transplantation, or VAD was high across the spectrum of congenital heart disease. While severe defects carry the highest risk, those with mild disease are still at greater risk than the general population.

Copyright © 2021 Elsevier Inc. All rights reserved.

Am J Cardiol: 14 Mar 2022; 167:111-117
Wright LK, Zmora R, Huang Y, Oster ME, ... Kochilas L, Kalogeropoulos A
Am J Cardiol: 14 Mar 2022; 167:111-117 | PMID: 34991844
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Abstract

Prognostic Role of Pulmonary Function in Patients With Heart Failure With Reduced Ejection Fraction.

Chang HC, Huang WM, Yu WC, Cheng HM, ... Chen CH, Sung SH

Background:
Both ventilatory abnormalities and pulmonary hypertension (PH) are frequently observed in patients with heart failure with reduced ejection fraction. We aim to investigate the association between ventilatory abnormalities and PH in heart failure with reduced ejection fraction, as well as their prognostic impacts. Methods and Results A total of 440 ambulatory patients (age, 66.2±15.8 years; 77% men) with left ventricular ejection fraction ≤40% who underwent comprehensive echocardiography and spirometry were enrolled. Total lung capacity, forced vital capacity, and forced expiratory volume in the first second were obtained. Pulmonary arterial systolic pressure was estimated. PH was defined as a pulmonary arterial systolic pressure of >50 mm Hg. The primary end point was all-cause mortality at 5 years. Patients with PH had significantly reduced total lung capacity, forced vital capacity, and forced expiratory volume in the first second. During a median follow-up of 25.9 months, there were 111 deaths. After accounting for age, sex, body mass index, renal function, smoking, left ventricular ejection fraction, and functional capacity, total lung capacity (hazard ratio [HR] per 1 SD, 0.66; 95% CI per 1 SD, 0.46-0.96), forced vital capacity (HR per 1 SD, 0.64; 95% CI per 1 SD, 0.48-0.84), and forced expiratory volume in the first second (HR per 1 SD, 0.72; 95% CI per 1 SD, 0.53-0.98) were all significantly correlated with mortality in patients without PH. Kaplan-Meier curve demonstrated impaired pulmonary function, defined as forced expiratory volume in the first second ≤58% of predicted or forced vital capacity ≤65% of predicted, was associated with higher mortality in patients without PH (HR, 2.85; 95% CI, 1.66-4.89), but not in patients with PH (HR, 1.05; 95% CI, 0.61-1.82).
Conclusions:
Ventilatory abnormality was more prevalent in patients with heart failure with reduced ejection fraction with PH than those without. However, such ventilatory defects were related to long-term survival only in patients without PH, regardless of their functional status.




J Am Heart Assoc: 14 Mar 2022:e023422; epub ahead of print
Chang HC, Huang WM, Yu WC, Cheng HM, ... Chen CH, Sung SH
J Am Heart Assoc: 14 Mar 2022:e023422; epub ahead of print | PMID: 35289186
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Abstract

Time in Target Range for Systolic Blood Pressure and Cardiovascular Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

Huang R, Lin Y, Liu M, Xiong Z, ... Zhuang X, Liao X

Background:
The association between blood pressure control and clinical outcomes is unclear among patients with heart failure with preserved ejection fraction. Both too high and too low of systolic blood pressure (SBP) have been reported to be related to poor clinical prognosis. This study aimed to assess the association between time in SBP target range and adverse clinical events among patients with heart failure with preserved ejection fraction. Methods and Results This study was a secondary analysis of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, a randomized clinical trial that compared the efficacy and safety of spironolactone in patients with heart failure with preserved ejection fraction. Time in target range (TTR) was calculated using linear interpolation, with the target range of SBP defined as 110 to 130 mm Hg. The association between TTR with adverse outcomes was estimated using multivariable Cox regression to adjust for multiple confounders. Participants with greater TTR were younger, more likely to be White, had less comorbidities, and lower body mass index. After adjusting for multiple covariates including mean SBP, 1-SD increment (38.3%) of TTR was significantly associated with a decreased risk of primary composite end point (hazard ratio [HR], 0.81 [0.73-0.90]), as well as a lower risk of all-cause mortality (HR, 0.81 [0.73-0.90]), cardiovascular death (HR, 0.78 [0.68-0.90]), and heart failure hospitalization (HR, 0.85 [0.74-0.97]). Results were similar when participants were categorized by TTR groups. Subgroup analyses showed that the associations were more significant in young people than in the old (Pinteraction=0.028).
Conclusions:
In patients with heart failure with preserved ejection fraction, greater time in SBP target range was statistically associated with a decreased risk of cardiovascular outcomes and mortality events beyond blood pressure level, especially among younger patients.




J Am Heart Assoc: 14 Mar 2022:e022765; epub ahead of print
Huang R, Lin Y, Liu M, Xiong Z, ... Zhuang X, Liao X
J Am Heart Assoc: 14 Mar 2022:e022765; epub ahead of print | PMID: 35289182
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Abstract

The Association of Improvement in Left Ventricular Ejection Fraction with Outcomes in Patients with Heart Failure with Reduced Ejection Fraction: Data from CHAMP-HF.

DeVore AD, Hellkamp AS, Thomas L, Albert NM, ... Hernandez AF, Fonarow GC
Aims
We assessed for an association between improvements in left ventricular ejection fraction (LVEF) and future outcomes, including health status, in routine clinical practice.
Methods and results
CHAMP-HF was a registry of outpatients with heart failure (HF) and LVEF <40%. Enrolled participants completed the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) at regular intervals and were followed as part of routine care. We assessed for associations between improvements in LVEF (>10%) over time and concurrent changes in KCCQ-12, as well as the subsequent risk of poor outcomes. We included 2092 participants in the study. They had the following characteristics: median age 67 years (25th , 75th percentile 58, 75), 29% female, median duration of HF 2.7 years (0.6, 6.8), and median baseline LVEF 30% (23, 35). Of the study participants, 689 (34%) had a >10% absolute improvement in LVEF. Participants with an LVEF improvement also had an improvement in KCCQ-12 overall summary score compared with participants without an LVEF improvement (+7.6 vs +3.5, adjusted effect estimate +4.1 [95% CI 2.3 to 5.7]). Similarly, subsequent all-cause death or HF hospitalization occurred in 12% in the LVEF improvement group vs 25% in the group without an LVEF improvement (adjusted HR 0.50, 95% CI 0.41 to 0.61).
Conclusion
In a large cohort of outpatients with chronic HF, improvements in LVEF were associated with improved health status and a reduced risk for future clinical events. These data underscore the importance of improvement in LVEF as a treatment target for medical interventions for patients with chronic HF.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 14 Mar 2022; epub ahead of print
DeVore AD, Hellkamp AS, Thomas L, Albert NM, ... Hernandez AF, Fonarow GC
Eur J Heart Fail: 14 Mar 2022; epub ahead of print | PMID: 35293088
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Abstract

Dronedarone for the Treatment of Atrial Fibrillation with Concomitant Heart Failure with Preserved and Mildly Reduced Ejection Fraction: Post-Hoc Analysis of the ATHENA Trial.

Vaduganathan M, Piccini JP, Camm AJ, Crijns HJGM, ... Wieloch M, Hohnloser SH
Aims
Limited therapeutic options are available for the management of atrial fibrillation/flutter (AF/AFL) with concomitant heart failure with preserved and mildly reduced ejection fraction. (HFpEF and HFmrEF). Dronedarone reduces the risk of cardiovascular events in patients with AF, but sparse data are available examining its role in patients with AF complicated by HFpEF and HFmrEF.
Methods and results
ATHENA was an international, multicenter trial that randomized 4,628 patients with paroxysmal or persistent AF/AFL and cardiovascular risk factors to dronedarone 400 mg twice daily versus placebo. We evaluated patients with 1) symptomatic HFpEF and HFmrEF (defined as LVEF>40%, evidence of structural heart disease, and New York Heart Association class II/III or diuretic use), 2) HF with reduced ejection fraction (HFrEF) or left ventricular dysfunction (LVEF≤40%), and 3) those without HF. We assessed effects of dronedarone vs placebo on death or cardiovascular hospitalization (primary endpoint), other key efficacy endpoints, and safety. Overall, 534 (12%) had HFpEF or HFmrEF, 422 (9%) had HFrEF or LV dysfunction, and 3,672 (79%) did not have HF. Patients with HFpEF and HFmrEF had a mean age of 73±9 years, 37% were women, and had a mean LVEF of 57±9%. Over 21±5 months mean follow-up, dronedarone consistently reduced risk of death or cardiovascular hospitalization (hazard ratio 0.76; 95% confidence interval 0.69-0.84) without heterogeneity based on HF status (Pinteraction >0.10). This risk reduction in the primary endpoint was consistent across the range of LVEF (as a continuous function) in HF without heterogeneity (Pinteraction =0.71). Rates of death, cardiovascular hospitalization, and HF hospitalization each directionally favored dronedarone vs. placebo in HFpEF and HFmrEF, but these treatment effects were not statistically significant.
Conclusions
Dronedarone is associated with reduced cardiovascular events in patients with paroxysmal or persistent AF/AFL and HF across the spectrum of LVEF, including among those with HFpEF and HFmrEF. These data support a rationale for a future dedicated and powered clinical trial to affirm the net clinical benefit of dronedarone in this population.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 14 Mar 2022; epub ahead of print
Vaduganathan M, Piccini JP, Camm AJ, Crijns HJGM, ... Wieloch M, Hohnloser SH
Eur J Heart Fail: 14 Mar 2022; epub ahead of print | PMID: 35293087
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Abstract

Heart Failure Quality of Care and In-Hospital Outcomes During the COVID-19 Pandemic Findings from the Get With The Guidelines-Heart Failure Registry.

Keshvani N, Mehta A, Alger HM, Rutan C, ... Fonarow GC, Pandey A
Aims
Assess heart failure (HF) in-hospital quality of care and outcomes before and during the COVID-19 pandemic.
Methods & results
Patients hospitalized for HF with ejection fraction (EF) <40% in American Heart Association Get With The Guidelines©-HF registry during pandemic (3/1/2020 - 4/1/2021) and pre-pandemic (2/1/2019 - 2/29/2020) periods were included. Adherence to HF process of care measures, in-hospital mortality, and length of stay (LOS) were compared in pre-pandemic vs. pandemic periods and patients with vs. without COVID-19. 42,004 pre-pandemic and 37,027 pandemic period patients (median age 68, 33% women, 58% White) were included without observed differences across clinical characteristics, comorbidities, vital signs, or EF. Utilization of guideline-directed medical therapy at discharge was comparable across both periods, with rates of ICD placement or prescription lower during the pandemic (vs. pre-pandemic period). In-hospital mortality (3.0% vs 2.5%, p<0.001) and LOS (mean 5.7 vs. 5.4 days, p<0.001) were higher during the pandemic vs pre-pandemic. The highest in-hospital mortality during the pandemic was observed among patients hospitalized in the Northeast region (3.4%). Among patients concurrently diagnosed with COVID-19 (N=549; 1.5%), adherence to ICD placement or prescription, prescription of aldosterone antagonist or ACE/ARB/ARNi at discharge were lower, and in-hospital mortality (8.2% vs. 3.0%, p<0.001) and length of stay (mean 7.7 days vs. 5.7 days, p<0.001) were higher than those without COVID-19.
Conclusion
Among GWTG-HF participating hospitals, patients hospitalized for HFrEF during the pandemic received similar care quality but experienced higher in-hospital mortality than the pre-pandemic period. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 13 Mar 2022; epub ahead of print
Keshvani N, Mehta A, Alger HM, Rutan C, ... Fonarow GC, Pandey A
Eur J Heart Fail: 13 Mar 2022; epub ahead of print | PMID: 35289038
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Impact:
Abstract

Health Status Improvement with Ferric Carboxymaltose in Heart Failure with Reduced Ejection Fraction and Iron Deficiency.

Butler J, Khan MS, Friede T, Jankowska EA, ... Anker SD, Ponikowski P
Aim
Intravenous ferric carboxymaltose (FCM) has been shown to improve overall quality of life in iron-deficient heart failure with reduced ejection fraction (HFrEF) patients at a trial population level. This FAIR-HF and CONFIRM-HF pooled analysis explored the likelihood of individual improvement or deterioration in Kansas City Cardiomyopathy Questionnaire (KCCQ) domains with FCM vs placebo and evaluated the stability of this response over time.
Methods
Changes vs baseline in KCCQ overall summary score (OSS), clinical summary score (CSS) and total symptom score (TSS) were assessed at weeks 12 and 24 in FCM and placebo groups . Mean between-group differences were estimated and individual responder analyses and analyses of response stability were performed.
Results
Overall, 760 (FCM: 454) patients were studied. At week 12, the mean improvement in KCCQ OSS was 10.6 points with FCM vs 4.8 points with placebo (least-square mean difference [95% confidence interval (CI)]: 4.36 [2.14;6.59] points). A higher proportion of patients on FCM vs placebo experienced a KCCQ OSS improvement of ≥5 (58.3% vs 43.5%; odds ratio [95% CI]: 1.81 [1.30;2.51]), ≥10 (42.4% vs 29.3%; 1.73 [1.23;2.43]) or ≥15 (32.1% vs 22.6%; 1.46 [1.02;2.11]) points. Differences were similar at week 24 and for CSS and TSS domains. Of FCM patients with a ≥5-, ≥10- or ≥15-point improvement in KCCQ OSS at week 12, >75% sustained this improvement at week 24.
Conclusion
Treatment of iron-deficient HFrEF patients with intravenous FCM conveyed clinically relevant improvements in health status at an individual-patient level; benefits were sustained over time in most patients. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 12 Mar 2022; epub ahead of print
Butler J, Khan MS, Friede T, Jankowska EA, ... Anker SD, Ponikowski P
Eur J Heart Fail: 12 Mar 2022; epub ahead of print | PMID: 35279929
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Abstract

Genetic and phenotypic profiling of supranormal ejection fraction reveals decreased survival and underdiagnosed heart failure.

Forrest IS, Rocheleau G, Bafna S, Argulian E, ... Natarajan P, Do R
Aims
Individuals with supranormal left ventricular ejection fraction (snLVEF; LVEF>70%) have increased mortality. However, the genetic and phenotypic profile of snLVEF remains unknown. This study aimed to determine the relationship of both snLVEF genetic risk and phenotype with survival and underdiagnosed heart failure (HF).
Methods and results
A snLVEF genetic risk score (GRS) was applied and cases of snLVEF were identified in 486,754 individuals across two population-based cohorts (BioMe Biobank and UK Biobank). The snLVEF GRS and phenotype were evaluated for association with survival, as well as HF diagnosis, markers, symptoms, and medications. Of 486,754 participants, the median age was 58 years, 20,069 (4.1%) died, and 10,043 (2.1%) had diagnosed HF. Both snLVEF GRS (hazard ratio [HR]=1.1 for top 10% versus bottom 10% GRS; P=0.002) and phenotype (HR=1.4; P=0.003) were associated with increased all-cause mortality. Both snLVEF GRS and phenotype were associated with reduced HF diagnosis (odds ratio [OR]=0.97 and OR=0.63, respectively; both P<0.002). However, the snLVEF GRS and phenotype were both associated with elevated brain natriuretic peptide (BNP) levels (146 and 185 pg/mL increase, respectively; P<0.001), including 268 out of 455 (59%) individuals with snLVEF phenotype who had BNP >100 pg/mL. Among 476,711 participants without HF diagnoses, snLVEF GRS and phenotype were associated with increased HF symptoms (e.g. exertional dyspnea OR=1.4 and OR=1.3; P<0.003) and HF medications (e.g. loop diuretic OR=1.2 and OR=1.03; P<0.02). Associations were consistent in hypertensive individuals without cardiac comorbidities.
Conclusions
Genetic predisposition to and presence of snLVEF are associated with decreased survival and underdiagnosed HF. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 11 Mar 2022; epub ahead of print
Forrest IS, Rocheleau G, Bafna S, Argulian E, ... Natarajan P, Do R
Eur J Heart Fail: 11 Mar 2022; epub ahead of print | PMID: 35278270
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Impact:
Abstract

Use of evidence-based therapy in heart failure with reduced ejection fraction across age strata.

Stolfo D, Lund LH, Becher PM, Orsini N, ... Sinagra G, Savarese G
Aims
In older patients guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (HFrEF; EF<40%) is not contraindicated, but adherence to guidelines is limited. We investigated the implementation of GDMT in HFrEF across different age strata in a large nationwide cohort.
Methods and results
Patients with HFrEF and HF duration ≥3 months registered in the Swedish HF Registry between 2000-2018 were analyzed according to age. Multivariable logistic and multinomial regressions were fitted to investigate factors associated with underuse/underdosing. Of 27,430 patients, 31% were <70, 34% 70-79 and 35% ≥80 years old. Use of treatments progressively decreased with increasing age. Use of renin-angiotensin-system/angiotensin receptor neprilysin inhibitors, beta-blockers and mineralocorticoid receptor antagonists was, respectively, 80%, 88% and 35% in age ≥80 years; 90%, 93% and 47% in age 70-79 years; and 95%, 95% and 54% in age <70 years. Among patients with an indication, use of implantable cardioverter defibrillator and cardiac resynchronization therapy (CRT) was, respectively, 7% and 23% in age ≥80; 22% and 42% in age 70-79; and 29% and 50% in age <70 years. Older patients were less likely treated with target doses of or combinations of HF medications. Except for CRT, after extensive adjustments, age was inversely associated with the likelihood of GDMT use and target dose achievement.
Conclusion
In HFrEF, gaps persist in the use of medications and devices. In disagreement with current recommendations, older patients remain undertreated. Improving strategies and a more individualized approach for implementing use of GDMT in HFrEF are required, in particular in older patients. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 11 Mar 2022; epub ahead of print
Stolfo D, Lund LH, Becher PM, Orsini N, ... Sinagra G, Savarese G
Eur J Heart Fail: 11 Mar 2022; epub ahead of print | PMID: 35278267
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Impact:
Abstract

Evidence-Based Process Performance Measures and Clinical Outcomes in Patients With Incident Heart Failure With Reduced Ejection Fraction: A Danish Nationwide Cohort Study.

Schjødt I, Johnsen SP, Strömberg A, DeVore AD, Valentin JB, Løgstrup BB
Background
Data on the association between quality of heart failure (HF) care and outcomes among patients with incident HF are sparse. We examined the association between process performance measures and clinical outcomes in patients with incident HF with reduced ejection fraction.
Methods
Patients with incident HF with reduced ejection fraction (n=10 966) between January 2008 and October 2015 were identified from the Danish HF Registry. Data from public registries were linked. Multivariable regression analyses were used to assess the association between 6 guideline-recommended HF care processes (New York Heart Association assessment, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists, exercise training, and patient education) and all-cause and HF readmission, all-cause and HF hospital days, and mortality within 3 to 12 months after HF diagnosis. The associations were analyzed according to the percentages of all relevant performance measures fulfilled for the individual patient (0%-50% [reference group], >50%-75%, and >75%-100%) and for the individual performance measures.
Results
Fulfilling >75% to 100% of the performance measures (n=5341 [48.7%]) was associated with lower risk of all-cause readmission (adjusted hazard ratio, 0.78 [95% CI, 0.68-0.89]) and HF readmission (adjusted hazard ratio, 0.71 [95% CI, 0.54-0.92]), lower use of all-cause hospital days (adjusted mean ratio, 0.73 [95% CI, 0.70-0.76]) and HF hospital days (adjusted mean ratio, 0.79 [95% CI, 0.70-0.89]), and lower mortality (adjusted hazard ratio, 0.42 [95% CI, 0.32-0.53]). A dose-response relationship was observed between fulfilling more performance measures and mortality (adjusted hazard ratio, 0.62 [95% CI, 0.49-0.77] fulfilling >50%-75% of the measures). Fulfilling individual performance measures, except mineralocorticoid receptor antagonist therapy, was associated with lower adjusted all-cause readmission, lower adjusted use of all-cause and HF hospital days, and lower adjusted mortality.
Conclusions
Fulfilling more process performance measures was associated with better clinical outcomes in patients with incident HF with reduced ejection fraction.



Circ Cardiovasc Qual Outcomes: 10 Mar 2022:CIRCOUTCOMES121007973; epub ahead of print
Schjødt I, Johnsen SP, Strömberg A, DeVore AD, Valentin JB, Løgstrup BB
Circ Cardiovasc Qual Outcomes: 10 Mar 2022:CIRCOUTCOMES121007973; epub ahead of print | PMID: 35272503
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Abstract

The GUIDE-HF trial of pulmonary artery pressure monitoring in heart failure: impact of the COVID-19 pandemic.

Zile MR, Desai AS, Costanzo MR, Ducharme A, ... Adamson PB, Lindenfeld J
Aims
During the coronavirus disease 2019 (COVID-19) pandemic, important changes in heart failure (HF) event rates have been widely reported, but few data address potential causes for these changes; several possibilities were examined in the GUIDE-HF study.
Methods and results
From 15 March 2018 to 20 December 2019, patients were randomized to haemodynamic-guided management (treatment) vs. control for 12 months, with a primary endpoint of all-cause mortality plus HF events. Pre-COVID-19, the primary endpoint rate was 0.553 vs. 0.682 events/patient-year in the treatment vs. control group [hazard ratio (HR) 0.81, P = 0.049]. Treatment difference was no longer evident during COVID-19 (HR 1.11, P = 0.526), with a 21% decrease in the control group (0.536 events/patient-year) and no change in the treatment group (0.597 events/patient-year). Data reflecting provider-, disease-, and patient-dependent factors that might change the primary endpoint rate during COVID-19 were examined. Subject contact frequency was similar in the treatment vs. control group before and during COVID-19. During COVID-19, the monthly rate of medication changes fell 19.2% in the treatment vs. 10.7% in the control group to levels not different between groups (P = 0.362). COVID-19 was infrequent and not different between groups. Pulmonary artery pressure area under the curve decreased -98 mmHg-days in the treatment group vs. -100 mmHg-days in the controls (P = 0.867). Patient compliance with the study protocol was maintained during COVID-19 in both groups.
Conclusion
During COVID-19, the primary event rate decreased in the controls and remained low in the treatment group, resulting in an effacement of group differences that were present pre-COVID-19. These outcomes did not result from changes in provider- or disease-dependent factors; pulmonary artery pressure decreased despite fewer medication changes, suggesting that patient-dependent factors played an important role in these outcomes. Clinical Trials.gov: NCT03387813.
Key questions
What factors explain the loss of treatment effect and reduction in heart failure events during COVID-19?
Key findings
The treatment effect change was not due to COVID-19-related events. Patient management was sustained but not intensified during COVID-19. Patient status improved during COVID-19 and pulmonary artery pressure reduced in both groups.
Take home message
Patient behaviour probably improved during COVID-19, given that patient status and pulmonary artery pressure improved during COVID-19 despite fewer medication changes and without increased contact from providers.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Eur Heart J: 09 Mar 2022; epub ahead of print
Zile MR, Desai AS, Costanzo MR, Ducharme A, ... Adamson PB, Lindenfeld J
Eur Heart J: 09 Mar 2022; epub ahead of print | PMID: 35266003
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Impact:
Abstract

Electrical management of heart failure: from pathophysiology to treatment.

Prinzen FW, Auricchio A, Mullens W, Linde C, Huizar JF
Electrical disturbances, such as atrial fibrillation (AF), dyssynchrony, tachycardia, and premature ventricular contractions (PVCs), are present in most patients with heart failure (HF). While these disturbances may be the consequence of HF, increasing evidence suggests that they may also cause or aggravate HF. Animal studies show that longer-lasting left bundle branch block, tachycardia, AF, and PVCs lead to functional derangements at the organ, cellular, and molecular level. Conversely, electrical treatment may reverse or mitigate HF. Clinical studies have shown the superiority of atrial and pulmonary vein ablation for rhythm control and AV nodal ablation for rate control in AF patients when compared with medical treatment. Ablation of PVCs can also improve left ventricular function. Cardiac resynchronization therapy (CRT) is an established adjunct therapy currently undergoing several interesting innovations. The current guideline recommendations reflect the safety and efficacy of these ablation therapies and CRT, but currently, these therapies are heavily underutilized. This review focuses on the electrical treatment of HF with reduced ejection fraction (HFrEF). We believe that the team of specialists treating an HF patient should incorporate an electrophysiologist in order to achieve a more widespread use of electrical therapies in the management of HFrEF and should also include individual conditions of the patient, such as body size and gender in therapy fine-tuning.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.

Eur Heart J: 09 Mar 2022; epub ahead of print
Prinzen FW, Auricchio A, Mullens W, Linde C, Huizar JF
Eur Heart J: 09 Mar 2022; epub ahead of print | PMID: 35265992
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Impact:
Abstract

Defining Changes in Physical Limitation from the Patient Perspective: Insights from the VITALITY-HFpEF Randomized Trial.

Butler J, Spertus JA, Bamber L, Khan MS, ... Armstrong PW, VITALITY-HFpEF Study Group
Background
Clinically important thresholds in patient-reported outcomes measures like the Kansas City Cardiomyopathy Questionnaire (KCCQ) have not been defined for patients with heart failure and preserved ejection fraction (HFpEF). The aim of this study was to estimate meaningful thresholds for improvement or worsening in the KCCQ-Physical Limitation Score (PLS) in patients with HFpEF.
Methods
In this pre-specified analysis from VITALITY-HFpEF, anchor- and distribution-based approaches were used to estimate thresholds for improvement or worsening in the KCCQ-PLS using Patient Global Impression of Change (PGIC) as an anchor. The KCCQ-PLS contains 6 elements, with each increment in response resulting in a change of 4.17 points when converted to a 0-100 scale. The mean change in KCCQ-PLS from baseline to week 12 was calculated for each PGIC group to estimate a meaningful within-patient change.
Results
Of 789 patients enrolled, 698 had complete KCCQ-PLS and PGIC data at week 12. The mean (±SD) changes in KCCQ-PLS corresponding to PGIC changes of \"a little better,\" \"better,\" and \"much better\" were 5.7±18.6, 11.6±19.3, and 18.4±25.3 points, respectively. The scores of patients who responded \"a little better\" (n=177) overlapped substantially with those who reported \"no change\" (n=193; mean change 2.8±18.9). The mean change in KCCQ-PLS for patients responding \"a little worse\" (n=32) was -2.6±18.0 points. The threshold for meaningful within-patient change in KCCQ-PLS based on distribution-based analyses was 12.3 points. Using area-under-curve (AUC) analyses of KCCQ-PLS, the sensitivity and specificity of a 4.17-point change were 0.61 and 0.57, for an 8.33-point change they were 0.49 and 0.64, and for a 12.5-point change were 0.44 and 0.72 for being at least a little better on the PGIC (AUC=0.54).
Conclusion
In the VITALITY-HFpEF trial, a change in KCCQ-PLS of ≥8.33 points (corresponding to an improvement in ≥2 response categories of KCCQ-PLS) may represent the minimal clinically important difference for improvement and a change of ≤ -4.17 points (corresponding to a worsening in ≥1 response category of KCCQ-PLS) may suggest deterioration in patients with HFpEF.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 09 Mar 2022; epub ahead of print
Butler J, Spertus JA, Bamber L, Khan MS, ... Armstrong PW, VITALITY-HFpEF Study Group
Eur J Heart Fail: 09 Mar 2022; epub ahead of print | PMID: 35274420
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Impact:
Abstract

Impaired Right Atrial Reserve Function in Heart Failure with Preserved Ejection Fraction.

Kagami K, Harada T, Yoshida K, Amanai S, ... Adachi T, Obokata M
Background
Patients with heart failure (HF) with preserved ejection fraction (HFpEF) have multiple cardiac reserve limitations during exercise. However, no data are available regarding RA reserve capacity in HFpEF. We sought to determine the association of right atrial (RA) reserve impairments with right ventricular (RV) function and exercise capacity in HFpEF and to explore its diagnostic value.
Methods
Patients with HFpEF (n=89) and control subjects without HF (n=108) underwent bicycle exercise echocardiography. RA reservoir, conduit, and booster pump strain at rest and during exercise were measured using speckle tracking echocardiography. In a subset, simultaneous expired gas analysis was performed to measure peak oxygen consumption (VO2).
Results
At rest, RA reservoir strain was lower in HFpEF patients than controls (27.0±17.1 vs. 38.6±17.1 %, p<0.0001) while RA conduit and booster pump strain were similar between groups. During peak exercise, patients with HFpEF displayed marked reserve limitations in RA reservoir and booster pump function compared to controls and the differences remained significant even after adjusting for confounding factors. During peak exercise, RA reservoir and booster pump strain were correlated with RV systolic function. Lower RA booster pump strain during exercise was also weakly associated with lower cardiac output (r=0.34, p<0.0001) and reduced peak VO2 (r=0.47, p<0.0001). RA reservoir strain during exercise had incremental diagnostic value to differentiate HFpEF from controls over the established HFpEF diagnostic algorithms and left-sided strain parameters.
Conclusions
Limitations in RA reservoir and booster pump function during exercise are present in HFpEF and the severity is associated with RV systolic reserve, poor cardiac output, and depressed exercise capacity. Exercise RA strain assessment may help the diagnosis of HFpEF.

Copyright © 2022. Published by Elsevier Inc.

J Am Soc Echocardiogr: 09 Mar 2022; epub ahead of print
Kagami K, Harada T, Yoshida K, Amanai S, ... Adachi T, Obokata M
J Am Soc Echocardiogr: 09 Mar 2022; epub ahead of print | PMID: 35283241
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Impact:
Abstract

Heart failure in adults with congenital heart disease.

Brida M, Lovrić D, Griselli M, Gil FR, Gatzoulis MA
Heart failure (HF) represents the leading cause of morbidity and mortality in adult patients with congenital heart disease. The nature of underlying congenital heart disease has bearing on timing and severity of HF and impacts on short- and long-term outcomes. HF can be subclinical, underscoring the need for close follow-up at tertiary centres with timely management of target hemodynamic lesions. Drug therapies have an effect in systemic left ventricle failure and are employed in acute HF for symptomatic relief. Data on elective drug therapy for the failing systemic right ventricle and/or Fontan circulation is currently lacking. Drugs such as angiotensin receptor blockers with neprilysin inhibitors or sodium-glucose co-transporter-2 inhibitors may show benefit. Cardiac resynchronization therapy, in appropriately selected patients, is considered a treatment option. Mechanical circulatory support and transplantation remain the last resource in highly selected patients. As the congenital heart disease population continues to grow and age, both outpatient and inpatient service for HF will continue to play a major role in the care of adult patients with congenital heart disease.

Copyright © 2022. Published by Elsevier B.V.

Int J Cardiol: 09 Mar 2022; epub ahead of print
Brida M, Lovrić D, Griselli M, Gil FR, Gatzoulis MA
Int J Cardiol: 09 Mar 2022; epub ahead of print | PMID: 35283250
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Impact:
Abstract

Prognostic Cardiac Magnetic Resonance Markers of Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy for Predicting Heart Failure Outcomes.

Chun KH, Oh J, Hong YJ, Yu HT, ... Kim YJ, Kang SM

Background:
Left ventricular (LV) involvement is frequently observed in arrhythmogenic cardiomyopathy (ACM). We investigated the association of LV myocardial assessment using cardiac magnetic resonance (CMR) with clinical outcomes including heart failure (HF)-related events in ACM. Methods and Results We retrospectively analyzed 60 patients with ACM between 2005 and 2020 according to the 2010 Task Force Criteria and assessed HF-related events (HF hospitalization, heart transplantation, and cardiac death) and ventricular tachycardia events. We analyzed CMR findings including late gadolinium enhancement (LGE) in all subjects and obtained mapping values (native T1, extracellular volume, and T2) on 30 (50%) patients out of them. Among the study population (mean age 49 years, 77% male), 41 (68%) patients had LV LGE. During a median follow-up of 34 months, there were 13 (22%) HF-related events, and 20 (30%) ventricular tachycardia events. Kaplan-Meier survival analysis revealed that HF-related events occurred only in patients with LV LGE (+) (versus LV LGE (-), log-rank P=0.006), and the events were not significantly different regarding right ventricular LGE (log-rank P>0.999). When categorized by median value for each mapping parameter, HF-related events occurred more in patients with higher native T1 (versus lower native T1, log-rank P=0.002), and higher T2 (versus lower T2, log-rank P=0.002), higher extracellular volume (versus lower extracellular volume, log-rank P=0.002). However, regarding ventricular tachycardia events, there were no significant differences according to these CMR markers.
Conclusions:
LV myocardial assessment using CMR with LGE imaging and native T1, T2, and extracellular volume markers were significantly associated with HF-related event risk in patients with ACM.




J Am Heart Assoc: 08 Mar 2022:e023167; epub ahead of print
Chun KH, Oh J, Hong YJ, Yu HT, ... Kim YJ, Kang SM
J Am Heart Assoc: 08 Mar 2022:e023167; epub ahead of print | PMID: 35261277
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Impact:
Abstract

Prognostic Value of Echocardiography for Heart Failure and Death in Adults with Chronic Kidney Disease.

Fitzpatrick JK, Ambrosy AP, Parikh RV, Tan TC, ... Go AS, CRIC Study Investigators
Background
Adults with chronic kidney disease (CKD) are at increased risk of heart failure (HF) morbidity and mortality. Despite well-characterized abnormalities in cardiac structure in CKD, it remains unclear how to optimally leverage echocardiography to risk stratify CKD patients.
Methods
We evaluated associations between echocardiographic parameters and risk of HF hospitalization and death using Cox proportional hazard models and forward selection with integrated discrimination improvement (IDI).
Results
The study included 3,505 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC). Mean age was 59±11 years, HF prevalence was 10%, and mean left ventricular (LV) ejection fraction (LVEF) was 54±9%. During mean 11 (interquartile range: 8 to 12) years of follow-up, event rates per 100-person years for HF hospitalizations and death, respectively, were 9.4 (95% Confidence Interval [CI]: 7.9-11.3) and 8.9 (95% CI: 7.6-10.5) for participants with LVEF <40%, 3.5 (95% CI: 3.0-4.2) and 4.6 (95% CI: 4.0-5.2) for patients with LVEF 40-49%, and 1.9 (95% CI: 1.7-2.1) and 3.1 (95% CI: 2.9-3.3) for patients with LVEF >50%. The rate of HF hospitalizations and deaths increased with lower eGFR across all LVEF categories. LV mass index, LVEF, and LV geometry had the strongest association with outcomes but provided modest incremental prognostic value to a baseline clinical model (IDI =0.14 and ΔAUC=0.017 for HF hospitalization, IDI =0.12 and ΔAUC=0.008 for death).
Conclusions
Baseline echocardiographic parameters are independently associated with increased risk of subsequent HF morbidity and mortality but provide only marginal incremental prognostic utility beyond clinical characteristics in the setting of CKD.

Copyright © 2022 Elsevier Inc. All rights reserved.

Am Heart J: 08 Mar 2022; epub ahead of print
Fitzpatrick JK, Ambrosy AP, Parikh RV, Tan TC, ... Go AS, CRIC Study Investigators
Am Heart J: 08 Mar 2022; epub ahead of print | PMID: 35278374
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Impact:
Abstract

Surrogate markers of gut dysfunction are related to heart failure severity and outcome - from the BIOSTAT-CHF consortium.

Israr MZ, Zhan H, Salzano A, Voors AA, ... Suzuki T, BIOSTAT-CHF investigators (full author list as appendix)
Background
The contribution of gut dysfunction to heart failure (HF) pathophysiology is not routinely assessed. We sought to investigate whether biomarkers of gut dysfunction would be useful in assessment of HF (e.g., severity, adverse outcomes) and risk stratification.
Methods
A panel of gut-related biomarkers including metabolites of the choline/carnitine- pathway [acetyl-L-carnitine, betaine, choline, γ-butyrobetaine, L-carnitine and trimethylamine-N-oxide (TMAO)] and the gut peptide, Trefoil Factor-3 (TFF-3), were investigated in 1,783 patients with worsening HF enrolled in the systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) cohort and associations with HF severity and outcomes, and use in risk stratification were assessed.
Results
Metabolites of the carnitine-TMAO pathway (acetyl-L-carnitine, γ-butyrobetaine, L-carnitine and TMAO) and TFF-3 were associated with the composite outcome of HF hospitalisation or all-cause mortality at 3 years [HR 2.04-2.93 (95% CI 1.30-4.71) p≤0.002]. Combining the carnitine-TMAO metabolites with TFF-3, as a gut dysfunction panel, showed a graded association; a greater number of elevated markers was associated with higher New York Heart Association class (p<0.001), higher plasma concentrations of B-type natriuretic peptide (p<0.001), and worse outcome [HR 1.90-4.58 (95% CI 1.19-6.74) p≤0.008]. Addition of gut dysfunction biomarkers to the contemporary BIOSTAT HF risk model also improved prediction for the aforementioned composite outcome [C-statistics p≤0.011, NRI 13.5-21.1 (95% CI 2.7-31.9) p≤0.014].
Conclusions
A panel of biomarkers of gut dysfunction showed graded association with severity of HF and adverse outcomes. Biomarkers as surrogate markers are potentially useful for assessment of gut dysfunction to HF pathophysiology and in risk stratification.

Copyright © 2022. Published by Elsevier Inc.

Am Heart J: 08 Mar 2022; epub ahead of print
Israr MZ, Zhan H, Salzano A, Voors AA, ... Suzuki T, BIOSTAT-CHF investigators (full author list as appendix)
Am Heart J: 08 Mar 2022; epub ahead of print | PMID: 35278373
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Impact:
Abstract

Variability in Coronary Artery Disease Testing for Patients With New-Onset Heart Failure.

Zheng J, Heidenreich PA, Kohsaka S, Fearon WF, Sandhu AT
Background
Coronary artery disease (CAD) is the most common cause of new-onset heart failure (HF). Although guidelines recommend ischemic evaluation in this population, testing has historically been underutilized.
Objectives
This study aimed to identify contemporary trends in CAD testing for patients with new-onset HF, particularly after publication of the STICHES (Surgical Treatment for Ischemic Heart Failure Extension Study), and to characterize geographic and clinician-level variability in testing patterns.
Methods
We determined the proportion of patients with incident HF who received CAD testing from 2004 to 2019 using an administrative claims database covering commercial insurance and Medicare. We identified demographic and clinical predictors of CAD testing during the 90 days before and after initial diagnosis. Patients were grouped by their county of residence to assess national variation. Patients were then linked to their primary care physician and/or cardiologist to evaluate variation across clinicians.
Results
Among 558,322 patients with new-onset HF, 34.8% underwent CAD testing and 9.3% underwent revascularization. After multivariable adjustment, patients who underwent CAD testing were more likely to be younger, male, diagnosed in an acute care setting, and have systolic dysfunction or recent cardiogenic shock. Incidence of CAD testing remained flat without significant change post-STICHES. Covariate-adjusted testing rates varied from 20% to 45% across counties. The likelihood of testing was higher among patients co-managed by a cardiologist (adjusted OR: 5.12; 95% CI: 4.98-5.27) but varied substantially across cardiologists (IQR: 50.9%-62.4%).
Conclusions
Most patients with new-onset HF across inpatient and outpatient settings did not receive timely testing for CAD. Substantial variability in testing persists across regions and clinicians.

Copyright © 2022 American College of Cardiology Foundation. All rights reserved.

J Am Coll Cardiol: 07 Mar 2022; 79:849-860
Zheng J, Heidenreich PA, Kohsaka S, Fearon WF, Sandhu AT
J Am Coll Cardiol: 07 Mar 2022; 79:849-860 | PMID: 35241218
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Impact:
Abstract

Association Between Dosing And Combination Use Of Medications And Outcomes In Heart Failure With Reduced Ejection Fraction: Data From The Swedish Heart Failure Registry.

D\'Amario D, Rodolico D, Rosano GM, Dahlström U, ... Lund LH, Savarese G
Aims
To assess the association between combination, dose and use of current guideline-recommended target doses (TD) of Renin-Angiotensin System inhibitors (RASi), Angiotensin Receptor Neprilysin inhibitors (ARNi) and β-blockers, and outcomes in a large and unselected contemporary cohort of patients with heart failure and reduced ejection fraction (HFrEF).
Methods and results
17 809 out-patients registered in the Swedish HF Registry (SwedeHF) from May 2000 to December 2018, with EF <40% and duration of HF ≥90 days were selected. Primary outcome was a composite of time to cardiovascular (CV) death and first HF hospitalization. Compared with no use of RASi or ARNi, the adjusted HR (95% CI) was 0.83 (0.76 to 0.91) with <50% of TD, 0.78 (0.71 to 0.86) with 50%-99%, and 0.73 (0.67 to 0.80) with ≥100% of TD. Compared with no use of β-blockers, the adjusted HR (95% CI) was 0.86 (0.76 to 0.91), 0.81 (0.74 to 0.89) and 0.74 (0.68 to 0.82) with <50%, 50%-99% and ≥100% of TD, respectively. Patients receiving both an ACEi/ARB/ARNi and a β-blocker at 50%-99% of TD had a lower adjusted risk of the primary outcome compared with patients only receiving one drug, i.e. ACEi/ARB/ARNi or β-blocker, even if this was at ≥100% of TD.
Conclusion
HFrEF patients using higher doses of RASi or ARNi and β-blockers had lower risk of CV death or HF hospitalization. Use of two drug classes at 50%-99% of TD dose was associated with lower risk than one drug class at 100% of TD.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 07 Mar 2022; epub ahead of print
D'Amario D, Rodolico D, Rosano GM, Dahlström U, ... Lund LH, Savarese G
Eur J Heart Fail: 07 Mar 2022; epub ahead of print | PMID: 35257446
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Abstract

Therapeutic and Prognostic Significance of Arachidonic Acid in Heart Failure.

Ma K, Yang J, Shao Y, Li P, ... Du J, Li Y
Background
Accurate prediction of death is an unmet need in patients with acute decompensated heart failure (HF). Arachidonic acid (AA) metabolites play an important role in the multiple pathophysiological processes. We aimed to develop an AA score to accurately predict mortality in patients with acute decompensated HF and explore the causal relationship between the AA predictors and HF.
Methods
The serum AA metabolites was measured in patients with acute decompensated HF (discovery cohort n=419; validation cohort n=386) by mass spectroscopy. We assessed the prognostic importance of AA metabolites for 1-year death using Cox regression and machine learning approaches. An machine learning-based AA score for predicting 1-year death was created and validated. We explored the mechanisms using transcriptome and functional experiments in a mouse model of early ischemic cardiomyopathy.
Results
Among the 27 AA metabolites, elevated 14,15-DHET/14,15-EET ratio was the strongest predictor of 1-year death (hazard ratio, 2.10, P=3.1×10-6). Machine learning-based AA score using a combination of the 14,15-DHET/14,15-EET ratio, 14,15-DHET, PGD2, and 9-HETE performed best (area under the curve [AUC]: 0.85). The machine learning-based AA score provided incremental information to predict mortality beyond BNP (B-type natriuretic peptide; ΔAUC: 0.19), clinical score (ΔAUC: 0.09), and preexisting ADHERE, Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure, and Get With The Guidelines Heart Failure scores (ΔAUC: 0.17, 0.17, 0.15, respectively). In the validation cohort, the AA score accurately predicted mortality (AUC:0.81). False-negative and false-positive findings, as classified by the BNP threshold, were correctly reclassified by the AA score (46.2% of false-negative and 84.5% of false-positive). In a murine model, the expression and enzymatic activity of sEH (soluble epoxide hydrolase) increased after myocardial infarction. Genetic deletion of sEH improved HF and the blockade of 14,15-EET abolished this cardioprotection. We mechanistically revealed the beneficial effect of 14,15-EET by impairing the activation of monocytes/macrophages.
Conclusions
Our studies propose that the AA score predicts death in patients with acute decompensated HF and inhibiting sEH serves as a therapeutic target for treating HF.
Registration
URL: https://www.
Clinicaltrials
gov; Unique identifier: NCT04108182.



Circ Res: 07 Mar 2022:CIRCRESAHA121320548; epub ahead of print
Ma K, Yang J, Shao Y, Li P, ... Du J, Li Y
Circ Res: 07 Mar 2022:CIRCRESAHA121320548; epub ahead of print | PMID: 35255710
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Abstract

Midpoint of energy intake, non-fasting time and cardiorespiratory fitness in heart failure with preserved ejection fraction and obesity.

Billingsley HE, Canada JM, Dixon DL, Kirkman DL, ... Abbate A, Carbone S
Background
Delayed time of evening meal is associated with favorable cardiorespiratory fitness (CRF) in patients with heart failure with preserved ejection fraction (HFpEF) and obesity. It is unknown, however, if increasing daily non-fasting time or delaying the midpoint of energy intake may also be associated with CRF.
Objective
Our aim was to examine whether a longer non-fasting time, delayed midpoint of energy intake, or both, are associated with greater CRF in patients with HFpEF and obesity.
Methods
We measured peak oxygen consumption (VO2), a measure of CRF, in 32 patients with HFpEF and obesity with cardiopulmonary exercise testing, and dietary intake using a five-pass 24-h dietary recall. Participants were divided into groups by having lesser (<11.6) or greater (≥11.6) periods of non-fasting time than the median and similarly, with earlier (<2:15 PM) or later (≥2:15 PM) than median midpoint of energy intake.
Results
Median non-fasting time was 11.6 [10.6-12.9] hours and midpoint of energy intake was 2:15 [1:04-3:00] PM. There were no differences in CRF between those with a shorter (<11.6) or longer (≥11.6) non-fasting time. Participants with a delayed midpoint of energy intake (≥2:15 PM) had greater peak VO2 and exercise time. Midpoint of energy intake (r = 0.444, P = 0.011) and time of last meal (r = 0.550, P = 0.001) displayed a positive association with peak VO2, but not non-fasting time nor time of first meal.
Conclusions
Delaying the midpoint of energy intake by postponing last meal is associated with better peak VO2 and exercise time in patients with HFpEF and obesity.

Copyright © 2022. Published by Elsevier B.V.

Int J Cardiol: 07 Mar 2022; epub ahead of print
Billingsley HE, Canada JM, Dixon DL, Kirkman DL, ... Abbate A, Carbone S
Int J Cardiol: 07 Mar 2022; epub ahead of print | PMID: 35276244
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Abstract

Jugular Venous Pressure Response to Inspiration for Risk Assessment of Heart Failure.

Shako D, Kawasaki T, Kasai K, Sato Y, ... Shiraishi H, Matoba S
Simplifying jugular venous pressure (JVP), visibility of the right internal jugular vein above the right clavicle in the sitting position, has been proposed in the management of heart failure (HF) because of its convenience. However, this method may be undervalued for the detection of mildly to moderately increased JVP. Increased JVP on inspiration, known as Kussmaul sign, may be a useful physical finding in this condition. This study consisted of 138 patients who were admitted for the management of HF. Using this simple method, JVP was assessed at rest in the sitting position before discharge; its response to inspiration was also examined if no high JVP was noted at rest. The primary outcome was a composite of cardiac death and hospitalization for worsening HF. Among all the patients, 16 patients (12%) had high JVP at rest and another 16 patients (12%) had high JVP not at rest but on inspiration. During a follow-up period of 249 ± 182 days, a primary outcome event occurred in 63 patients (46%). The incidence of adverse cardiac events was higher in patients with a high JVP at rest (69%; hazard ratio 3.31, 95% confidence interval 1.64 to 6.67, p = 0.0009) and in patients with a high JVP on inspiration (56%; hazard ratio 2.18, 95% confidence interval 1.02 to 4.63, p = 0.043) than in patients without a high JVP in both conditions (41%). In conclusion, a high JVP not only at rest but also on inspiration was associated with a poor prognosis. The response of JVP to inspiration using this simple technique of physical examination may be a new approach in the management of HF.

Copyright © 2022 Elsevier Inc. All rights reserved.

Am J Cardiol: 07 Mar 2022; epub ahead of print
Shako D, Kawasaki T, Kasai K, Sato Y, ... Shiraishi H, Matoba S
Am J Cardiol: 07 Mar 2022; epub ahead of print | PMID: 35277252
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Abstract

Combining Minimally Invasive Surgery With Ultra-Fast-Track Anesthesia in HeartMate 3 Patients: A Pilot Study.

Ahmad U, Khattab MA, Schaelte G, Goetzenich A, ... Schnoering H, Zayat R
Background
Minimally invasive surgery for left ventricular assist device implantation may have advantages over conventional sternotomy (CS). Additionally, ultra-fast-track anesthesia has been linked to better outcomes after cardiac surgery. This study summarizes our early experience of combining minimally invasive surgery with ultra-fast-track anesthesia (MIFTA) in patients receiving HeartMate 3 devices and compares the outcomes between MIFTA and CS.
Methods
From October 2015 to January 2019, 18 of 49 patients with Interagency Registry for Mechanically Assisted Circulatory Support profiles >1 underwent MIFTA for HeartMate 3 implantation. For bias reduction, propensity scores were calculated and used as a covariate in a regression model to analyze outcomes. Weighted parametric survival analysis was performed.
Results
In the MIFTA group, intensive care unit stays were shorter (mean difference, 8 days [95% CI, 4-13]; P<0.001), and the incidences of pneumonia and right heart failure were lower than those in the CS group (odds ratio, 1.36 [95% CI, 1.01-1.75]; P=0.016, respectively). At 6 and 12 hours postoperatively, MIFTA patients had a better hemodynamic performance with lower pulmonary wedge pressure (mean difference, 2.23 mm Hg [95% CI, 0.41-4.06]; P=0.028) and a higher right ventricular stroke work index (mean difference, -1.49 g·m/m2 per beat [95% CI, -2.95 to -0.02]; P=0.031). CS patients had a worse right heart failure-free survival rate (hazard ratio, 2.35 [95% CI, 0.96-5.72]; P<0.01).
Conclusions
Compared with CS, MIFTA is a beneficial approach for non-Interagency Registry for Mechanically Assisted Circulatory Support 1 HeartMate 3 patients with lower adverse event incidences, better hemodynamic performance, and preserved right heart function. Future large multicentric investigations are required to verify MIFTA\'s effects on outcomes.



Circ Heart Fail: 06 Mar 2022:CIRCHEARTFAILURE121008358; epub ahead of print
Ahmad U, Khattab MA, Schaelte G, Goetzenich A, ... Schnoering H, Zayat R
Circ Heart Fail: 06 Mar 2022:CIRCHEARTFAILURE121008358; epub ahead of print | PMID: 35249368
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Abstract

Short-term PM exposure and early-readmission risk: a retrospective cohort study in North Carolina heart failure patients.

Wyatt LH, Weaver AM, Moyer J, Schwartz JD, ... Cascio WE, Ward-Caviness C
Background
Short-term changes in ambient fine particulate matter (PM2.5) increase the risk for unplanned hospital readmissions. However, this association has not been fully evaluated for high-risk patients or examined to determine if the readmission risk differs based on time since discharge. Here we investigate the relation between ambient PM2.5 and 30-day readmission risk in heart failure (HF) patients using daily time windows and examine how this risk varies with respect to time following discharge.
Methods
We performed a retrospective cohort study of 17,674 patients with a recorded HF diagnosis between 2004 and 2016. The cohort was identified using the EPA CARES electronic health record resource. The association between ambient daily PM2.5 (μg/m3) concentration and 30-day readmissions was evaluated using time-dependent Cox proportional hazard models. PM2.5 associated readmission risk was examined throughout the 30-day readmission period and for early readmissions (1-3 days post-discharge). Models for 30-day readmissions included a parametric continuous function to estimate the daily PM2.5 associated readmission hazard. Fine-resolution ambient PM2.5 data were assigned to patient residential address and hazard ratios are expressed per 10 μg/m3 of PM2.5. Secondary analyses examined potential effect modification based on the time after a HF diagnosis, urbanicity, medication prescription, comorbidities, and type of HF.
Results
The hazard of a PM2.5-related readmission within three days of discharge was 1.33 (95% CI 1.18-1.51). This PM2.5 readmission hazard was slightly elevated in patients residing in non-urban areas (1.43, 95%CI 1.22-1.67) and for HF patients without a beta-blocker prescription prior to the readmission (1.35; 95% CI 1.19-1.53).
Conclusion
Our findings add to the evidence indicating substantial air quality-related health risks in individuals with underlying cardiovascular disease. Hospital readmissions are key metrics for patients and providers alike. As a potentially modifiable risk factor, air pollution-related interventions may be enacted that might assist in reducing costly and burdensome unplanned readmissions.

Published by Elsevier Inc.

Am Heart J: 05 Mar 2022; epub ahead of print
Wyatt LH, Weaver AM, Moyer J, Schwartz JD, ... Cascio WE, Ward-Caviness C
Am Heart J: 05 Mar 2022; epub ahead of print | PMID: 35263652
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Abstract

Cardiac Structure and Function and Diabetes-Related Risk of Death or Heart Failure in Older Adults.

Inciardi RM, Claggett B, Gupta DK, Cheng S, ... Shah AM, Skali H

Background:
Whether cardiac structure and function abnormalities associated with dysglycemia are sufficient to explain the increased risk of death or heart failure (HF) remains unclear. Methods and Results We analyzed 6059 participants (mean age, 75±5 years; 58% women; and 22% Black individuals) who attended the ARIC (Atherosclerosis Risk in Communities) study visit 5 examination (2011-2013). Participants were categorized as no diabetes, pre-diabetes, and diabetes (on the basis of medical history and glycated hemoglobin values). We assessed whether diabetes modified the association between echocardiographic measures of cardiac structure and function and the composite of all-cause death or HF hospitalization and then estimated the extent to which the increased risk of the composite outcome associated with diabetes was explained by cardiac structure and function. Diabetes was prevalent in 33.5% of the subjects. Death or HF occurred in 1111 (18%) at a rate of 3.6 per 100 person-years. Both measures of cardiac structure and function and diabetes status were significantly associated with worse prognosis after accounting for clinical confounders. While diabetes was consistently associated with a higher risk of events, it did not significantly modify the association between cardiac abnormalities and the risk of death or HF, except for subjects with higher left atrial volume who showed higher relative risk of events (P for interaction <0.001). Measures of cardiac structure and function accounted for ≈16% of the increased risk of death or HF associated with diabetes. Similar results were observed analyzing subjects without prevalent heart disease.
Conclusions:
In a biracial cohort of older adults, the increased risk of events associated with diabetes was partially explained by cardiac structure and function abnormalities.




J Am Heart Assoc: 04 Mar 2022:e022308; epub ahead of print
Inciardi RM, Claggett B, Gupta DK, Cheng S, ... Shah AM, Skali H
J Am Heart Assoc: 04 Mar 2022:e022308; epub ahead of print | PMID: 35253447
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Abstract

Mitochondrial Creatine Kinase Attenuates Pathologic Remodeling in Heart Failure.

Keceli G, Gupta A, Sourdon J, Gabr R, ... Paolocci N, Weiss RG
Background
Abnormalities in cardiac energy metabolism occur in heart failure (HF) and contribute to contractile dysfunction, but their role, if any, in HF-related pathologic remodeling is much less established. CK (creatine kinase), the primary muscle energy reserve reaction which rapidly provides ATP at the myofibrils and regenerates mitochondrial ADP, is down-regulated in experimental and human HF. We tested the hypotheses that pathologic remodeling in human HF is related to impaired cardiac CK energy metabolism and that rescuing CK attenuates maladaptive hypertrophy in experimental HF.
Methods
First, in 27 HF patients and 14 healthy subjects, we measured cardiac energetics and left ventricular remodeling using noninvasive magnetic resonance 31P spectroscopy and magnetic resonance imaging, respectively. Second, we tested the impact of metabolic rescue with cardiac-specific overexpression of either Ckmyofib (myofibrillar CK) or Ckmito (mitochondrial CK) on HF-related maladaptive hypertrophy in mice.
Results
In people, pathologic left ventricular hypertrophy and dilatation correlate closely with reduced myocardial ATP levels and rates of ATP synthesis through CK. In mice, transverse aortic constriction-induced left ventricular hypertrophy and dilatation are attenuated by overexpression of CKmito, but not by overexpression of CKmyofib. CKmito overexpression also attenuates hypertrophy after chronic isoproterenol stimulation. CKmito lowers mitochondrial reactive oxygen species, tissue reactive oxygen species levels, and upregulates antioxidants and their promoters. When the CK capacity of CKmito-overexpressing mice is limited by creatine substrate depletion, the protection against pathologic remodeling is lost, suggesting the ADP regenerating capacity of the CKmito reaction rather than CK protein per se is critical in limiting adverse HF remodeling.
Conclusions
In the failing human heart, pathologic hypertrophy and adverse remodeling are closely related to deficits in ATP levels and in the CK energy reserve reaction. CKmito, sitting at the intersection of cardiac energetics and redox balance, plays a crucial role in attenuating pathologic remodeling in HF. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00181259.



Circ Res: 03 Mar 2022; 130:741-759
Keceli G, Gupta A, Sourdon J, Gabr R, ... Paolocci N, Weiss RG
Circ Res: 03 Mar 2022; 130:741-759 | PMID: 35109669
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