Topic: Heart Failure

Abstract
<div><h4>Longer-Term Effects of Remote Patient Management Following Hospital Discharge After Acute Systolic Heart Failure: The Randomized E-INH Trial.</h4><i>Angermann CE, Sehner S, Faller H, Güder G, ... Störk ST, INH Study Group and of the Competence Network Heart Failure</i><br /><b>Background</b><br />The randomized INH (Interdisciplinary Network Heart Failure) trial (N = 715) reported that 6 months\' remote patient management (RPM) (HeartNetCare-HF) did not reduce the primary outcome (time to all-cause death/rehospitalization) vs usual care (UC) in patients discharged after admission for acute heart failure, but suggested lower mortality and better quality of life in the RPM group.<br /><b>Objectives</b><br />The Extended (E)-INH trial investigated the effects of 18 months\' HeartNetCare-HF on the same primary outcome in an expanded population (N = 1,022) and followed survivors up to 60 months (primary outcome events) or up to 120 months (mortality) after RPM termination.<br /><b>Methods</b><br />Eligible patients aged ≥18 years, hospitalized for acute heart failure, and with predischarge ejection fraction ≤40% were randomized to RPM (RPM+UC; n = 509) or control (UC; n = 513). Follow-up visits were every 6 months during RPM, and then at 36, 60, and 120 months.<br /><b>Results</b><br />The primary outcome did not differ between groups at 18 months (60.7% [95% CI: 56.5%-65.0%] vs 61.2% [95% CI: 57.0%-65.4%]) or 60 months (78.1% [95% CI: 74.4%-81.6%] vs 82.8% [95% CI: 79.5%-86.0%]). At 60 and 120 months, all-cause mortality was lower in patients previously undergoing RPM (41.1% [95% CI: 37.0%-45.5%] vs 47.4% [95% CI: 43.2%-51.8%]; P = 0.040 and 64.0% [95% CI: 59.8%-68.2%] vs 69.6% [95% CI: 65.6%-73.5%]; P = 0.019). At all visits, health-related quality of life was better in patients exposed to HeartNetCare-HF vs UC.<br /><b>Conclusions</b><br />Although 18 months\' HeartNetCare-HF did not significantly reduce the primary outcome of death or rehospitalization at 60 months, lower 120-month mortality in patients previously undergoing HeartNetCare-HF suggested beneficial longer-term effects, although the possibility of a chance finding remains.<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 01 Mar 2023; 11:191-206</small></div>
Angermann CE, Sehner S, Faller H, Güder G, ... Störk ST, INH Study Group and of the Competence Network Heart Failure
JACC Heart Fail: 01 Mar 2023; 11:191-206 | PMID: 36718715
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<div><h4>Epidemiology and Outcomes of Aortic Stenosis in Acute Decompensated Heart Failure: The ARIC Study.</h4><i>Sivaraj K, Arora S, Hendrickson M, Slehria T, ... Rosamond W, Vavalle JP</i><br /><b>Background</b><br />Few studies characterize the epidemiology and outcomes of aortic stenosis (AS) in acute decompensated heart failure (ADHF). This study investigates the significance of AS in contemporary patients who have experienced an ADHF hospitalization.<br /><b>Methods</b><br />The ARIC study (Atherosclerosis Risk in Communities) surveilled ADHF hospitalizations for residents ≥55 years of age in 4 US communities. ADHF cases were stratified by left ventricular ejection fraction (LVEF). Demographic differences in AS burden and the association of varying AS severities with mortality were estimated using multivariable logistic regression.<br /><b>Results</b><br />From 2005 through 2014, there were 3597 (weighted n=16 692) ADHF hospitalizations of which 48.6% had an LVEF <50% and 51.4% an LVEF ≥50%. AS prevalence was 12.1% and 18.7% in those with an LVEF <50% and ≥50%, respectively. AS was less likely in Black than White patients regardless of LVEF: LVEF <50% (odds ratio [OR], 0.34 [95% CI, 0.28-0.42]); LVEF ≥50% (OR, 0.51 [95% CI, 0.44-0.59]). Higher AS severity was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.16 [95% CI, 1.04-1.28]); LVEF ≥50% (OR, 1.40 [95% CI, 1.28-1.54]). Sensitivity analyses excluding severe AS patients detected that mild/moderate AS was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.23 [95% CI, 1.02-1.47]); LVEF ≥50% (OR, 1.31 [95% CI, 1.14-1.51]).<br /><b>Conclusions</b><br />Among patients who have experienced an ADHF hospitalization, AS is prevalent and portends poor mortality outcomes. Notably, mild/moderate AS is independently associated with 1-year mortality in this high-risk population.<br /><br /><br /><br /><small>Circ Heart Fail: 03 Feb 2023:e009653; epub ahead of print</small></div>
Sivaraj K, Arora S, Hendrickson M, Slehria T, ... Rosamond W, Vavalle JP
Circ Heart Fail: 03 Feb 2023:e009653; epub ahead of print | PMID: 36734224
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<div><h4>Effect of bariatric surgery on the incidence of heart failure: A propensity score matched nationwide cohort study.</h4><i>Kostanjsek L, Ardissino M, Moussa O, Rayes B, ... Collins P, Purkayastha S</i><br /><b>Background</b><br />Bariatric surgery results in significant weight loss and a reduction in the incidence of cardiovascular disease in patients with obesity; however, relatively little research considers its effect on the incidence of heart failure (HF). We aimed to determine whether bariatric surgery reduces the incidence of HF in patients with obesity, compared to non-surgical management.<br /><b>Methods</b><br />A propensity-score matched, retrospective cohort study using patients records from the nationwide Clinical Practice Research Database (CPRD) was conducted. 3052 patients who received bariatric surgery were matched with 3052 patients who did not, according to propensity to receive bariatric surgery, determined through a logistic regression model. Patients were eligible if >18 years old, BMI > 35 kg/m<sup>2</sup>, and no prior diagnosis of HF. The pre-defined primary endpoint was the development of new HF, and secondary endpoints were all-cause mortality and hospitalisations due to HF.<br /><b>Results</b><br />Patients who received bariatric surgery had a significantly lower incidence of new HF (hazard ratio 0.45, 95% confidence interval 0.28-0.73, p = 0.0011) and all-cause mortality (hazard ratio 0.56, 95% confidence interval 0.38-0.83, p = 0.0036).<br /><b>Conclusions</b><br />This study provides evidence of lower rates of HF and all-cause mortality in patients who undergo bariatric surgery, compared to propensity-score matched controls. Future studies to understand the mechanism(s) involved in this reduction and explore the lifetime benefits in high-risk cohorts are paramount.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 02 Feb 2023; epub ahead of print</small></div>
Kostanjsek L, Ardissino M, Moussa O, Rayes B, ... Collins P, Purkayastha S
Int J Cardiol: 02 Feb 2023; epub ahead of print | PMID: 36738843
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<div><h4>Effect of Personalized Accelerated Pacing on Quality of Life, Physical Activity, and Atrial Fibrillation in Patients With Preclinical and Overt Heart Failure With Preserved Ejection Fraction: The myPACE Randomized Clinical Trial.</h4><i>Infeld M, Wahlberg K, Cicero J, Plante TB, ... Lustgarten DL, Meyer M</i><br /><b>Importance</b><br />Patients with heart failure with preserved ejection fraction (HFpEF) with a pacemaker may benefit from a higher, more physiologic backup heart rate than the nominal 60 beats per minute (bpm) setting.<br /><b>Objective</b><br />To assess the effects of a moderately accelerated personalized backup heart rate compared with 60 bpm (usual care) in patients with preexisting pacemaker systems that limit pacemaker-mediated dyssynchrony.<br /><b>Design, setting, and participants</b><br />This blinded randomized clinical trial enrolled patients with stage B and C HFpEF from the University of Vermont Medical Center pacemaker clinic between June 2019 and November 2020. Analysis was modified intention to treat.<br /><b>Interventions</b><br />Participants were randomly assigned to personalized accelerated pacing or usual care and were followed up for 1 year. The personalized accelerated pacing heart rate was calculated using a resting heart rate algorithm based on height and modified by ejection fraction.<br /><b>Main outcomes and measures</b><br />The primary outcome was the serial change in Minnesota Living with Heart Failure Questionnaire (MLHFQ) score. Secondary end points were changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, pacemaker-detected physical activity, atrial fibrillation from baseline, and adverse clinical events.<br /><b>Results</b><br />Overall, 107 participants were randomly assigned to the personalized accelerated pacing (n = 50) or usual care (n = 57) groups. The median (IQR) age was 75 (69-81) years, and 48 (48%) were female. Over 1-year follow-up, the median (IQR) pacemaker-detected heart rate was 75 (75-80) bpm in the personalized accelerated pacing arm and 65 (63-68) bpm in usual care. MLHFQ scores improved in the personalized accelerated pacing group (median [IQR] baseline MLHFQ score, 26 [8-45]; at 1 month, 15 [2-25]; at 1 year, 9 [4-21]; P < .001) and worsened with usual care (median [IQR] baseline MLHFQ score, 19 [6-42]; at 1 month, 23 [5-39]; at 1 year, 27 [7-52]; P = .03). In addition, personalized accelerated pacing led to improved changes in NT-proBNP levels (mean [SD] decrease of 109 [498] pg/dL vs increase of 128 [537] pg/dL with usual care; P = .02), activity levels (mean [SD], +47 [67] minutes per day vs -22 [35] minutes per day with usual care; P < .001), and device-detected atrial fibrillation (27% relative risk reduction compared with usual care; P = .04) over 1-year of follow-up. Adverse clinical events occurred in 4 patients in the personalized accelerated pacing group and 11 patients in usual care.<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />In this study, among patients with HFpEF and pacemakers, treatment with a moderately accelerated, personalized pacing rate was safe and improved quality of life, NT-proBNP levels, physical activity, and atrial fibrillation compared with the usual 60 bpm setting.<br /><b>Trial registration</b><br />ClinicalTrials.gov Identifier: NCT04721314.<br /><br /><br /><br /><small>JAMA Cardiol: 01 Feb 2023; epub ahead of print</small></div>
Abstract
<div><h4>Worsening Heart Failure: Nomenclature, Epidemiology, and Future Directions: JACC Review Topic of the Week.</h4><i>Greene SJ, Bauersachs J, Brugts JJ, Ezekowitz JA, ... Zieroth S, Butler J</i><br /><AbstractText>Heart failure (HF) is a progressive disease characterized by variable durations of symptomatic stability often punctuated by episodes of worsening despite continued therapy. These periods of clinical worsening are increasingly recognized as a distinct phase in the history of HF, termed worsening HF (WHF). The definition of WHF continues to evolve from a historical focus solely on hospitalization to now include nonhospitalization events (eg, need for intravenous diuretic therapy in the emergency or outpatient setting). Most HF clinical trials to date have had HF hospitalization and death as primary endpoints, and only recently, some studies have included other WHF events regardless of location of care. This article reviews the evolution of the WHF definition, highlights the importance of considering the onset of WHF as an event that marks a new phase of HF, summarizes the latest clinical trials investigating novel therapies, and outlines unmet needs regarding identification and treatment of WHF.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 31 Jan 2023; 81:413-424</small></div>
Greene SJ, Bauersachs J, Brugts JJ, Ezekowitz JA, ... Zieroth S, Butler J
J Am Coll Cardiol: 31 Jan 2023; 81:413-424 | PMID: 36697141
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<div><h4>Impact of ferric carboxymaltose for iron deficiency at discharge after heart failure hospitalisation: A European multinational economic evaluation.</h4><i>McEwan P, Harrison C, Binnie R, Lewis RD, ... Ponikowski P, Jankowska EA</i><br /><b>Aims</b><br />Iron deficiency (ID) is comorbid in up to 50% patients with heart failure (HF) and exacerbates disease burden. Ferric carboxymaltose (FCM) reduced HF hospitalisations and improved quality of life when used to treat ID at discharge in patients hospitalised for acute HF with left-ventricular ejection fraction of <50% in the AFFIRM-AHF trial. We quantified the effect of FCM on burden of disease and the wider pharmacoeconomic implications in France, Germany, Poland, Spain and Sweden.<br /><b>Methods and results</b><br />The per country eligible population was calculated, aligning with the ESC 2021 HF guidelines and the AFFIRM-AHF trial. Changes in burden of disease with FCM versus standard of care (SoC) were represented by disability-adjusted life years (DALYs), hospitalisation episodes and bed days, using AFFIRM-AHF data. A Markov model was adapted to each country to estimate cost-effectiveness and combined with epidemiology data to calculate the impact on healthcare budgets. Between 335 (Sweden) and 13,237 (Germany) DALYs were predicted to be avoided with FCM use annually. Fewer hospitalisations and shorter lengths of stay associated with FCM compared to SoC were projected to result in substantial annual savings in bed days, from 5,215 in Sweden to 205,630 in Germany. In all countries, FCM was predicted to be dominant (cost saving with gains in quality-adjusted life years), resulting in net savings to healthcare budgets within one year.<br /><b>Conclusions</b><br />This comprehensive evaluation of FCM therapy highlights the potential benefits that could be realised through implementation of the ESC HF guideline recommendations regarding ID treatment. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 31 Jan 2023; epub ahead of print</small></div>
McEwan P, Harrison C, Binnie R, Lewis RD, ... Ponikowski P, Jankowska EA
Eur J Heart Fail: 31 Jan 2023; epub ahead of print | PMID: 36718652
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<div><h4>Growth Differentiation Factor-15 Predicts Mortality and Heart Failure Exacerbation But Not Ventricular Arrhythmias in Patients With Cardiomyopathy.</h4><i>Binder MS, Yanek LR, Yang W, Butcher B, ... Tomaselli GF, Barth AS</i><br /><AbstractText><br /><b>Background:</b><br/>Heart failure (HF) has been increasing in prevalence, and a need exists for biomarkers with improved predictive and prognostic ability. GDF-15 (growth differentiation factor-15) is a novel biomarker associated with HF mortality, but no serial studies of GDF-15 have been conducted. This study aimed to investigate the association between GDF-15 levels over time and the occurrence of ventricular arrhythmias, HF hospitalizations, and all-cause mortality. Methods and Results We used a retrospective case-control design to analyze 148 patients with ischemic and nonischemic cardiomyopathies and primary prevention implantable cardioverter-defibrillator (ICD) from the PROSe-ICD (Prospective Observational Study of the ICD in Sudden Cardiac Death Prevention) cohort. Patients had blood drawn every 6 months and after each appropriate ICD therapy and were followed for a median follow-up of 4.6 years, between 2005 to 2019. We compared serum GDF-15 levels within ±90 days of an event among those with a ventricular tachycardia/fibrillation event requiring ICD therapies and those hospitalized for decompensated HF. A comparator/control group comprised patients with GDF-15 levels available during 2-year follow-up periods without events. Median follow-up was 4.6 years in the 148 patients studied (mean age 58±12, 27% women). The HF cohort had greater median GDF-15 values within 90 days (1797 pg/mL) and 30 days (2039 pg/mL) compared with the control group (1062 pg/mL, both <i>P</i><0.0001). No difference was found between the ventricular tachycardia/fibrillation subgroup within 90 days (1173 pg/mL, <i>P</i>=0.60) or 30 days (1173 pg/mL, <i>P</i>=0.78) and the control group. GDF-15 was also significantly predictive of mortality (hazard ratio, 3.17 [95% CI, 2.33-4.30]). <br /><b>Conclusions:</b><br/>GDF-15 levels are associated with HF hospitalization and mortality but not ventricular arrhythmic events.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 31 Jan 2023:e8023; epub ahead of print</small></div>
Binder MS, Yanek LR, Yang W, Butcher B, ... Tomaselli GF, Barth AS
J Am Heart Assoc: 31 Jan 2023:e8023; epub ahead of print | PMID: 36718879
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<div><h4>Cost-effectiveness of dapagliflozin and empagliflozin for treatment of heart failure with reduced ejection fraction.</h4><i>Nguyen BN, Mital S, Bugden S, Nguyen HV</i><br /><b>Background</b><br />The differences in cost and efficacy between dapagliflozin and empagliflozin in combination with standard of care (SoC) raise the question of which regimen would be cost-effective in treating heart failure with reduced ejection fraction (HFrEF). This study evaluates the cost-effectiveness of dapagliflozin plus SoC (dapagliflozin-SoC) versus empagliflozin plus SoC (empagliflozin-SoC) or SoC alone for treatment of HFrEF.<br /><b>Methods</b><br />We developed a Markov model to estimate the cost-effectiveness of dapagliflozin-SoC, empagliflozin-SoC, and SoC alone from the healthcare system perspective over a lifetime horizon. Data on efficacy of dapagliflozin-SoC, empagliflozin-SoC, and SoC were obtained from randomized controlled trials. Costs were measured in 2022 US dollars, and effectiveness was measured in quality-adjusted life years (QALYs).<br /><b>Results</b><br />Among three strategies, dapagliflozin-SoC was the most cost-effective strategy and dominated empagliflozin-SoC in an extended sense. Compared with SoC alone, dapagliflozin-SoC and empagliflozin-SoC had incremental cost-effectiveness ratios (ICER) of $56,782 and $89,258 per QALY, respectively. Dapagliflozin-SoC cost more $5524 but yielded more 0.20 QALYs than empagliflozin-SoC, with the ICER of $27,861 per QALY. The cost-effectiveness of dapagliflozin-SoC, empagliflozin-SoC, and SoC alone did not depend on diabetic status. However, empagliflozin-SoC was no longer cost-effective versus SoC alone in HFrEF patients without CKD, and dapagliflozin-SoC was not cost-effective versus empagliflozin-SoC in HFrEF patients with CKD.<br /><b>Conclusion</b><br />Dapagliflozin-SoC was cost-effective versus empagliflozin-SoC or SoC alone for treatment of HFrEF.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 31 Jan 2023; epub ahead of print</small></div>
Nguyen BN, Mital S, Bugden S, Nguyen HV
Int J Cardiol: 31 Jan 2023; epub ahead of print | PMID: 36736672
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<div><h4>Eligibility for sotagliflozin in a real-world heart failure population based on the SOLOIST-WHF trial enrolment criteria: Data from the swedish heart failure registry.</h4><i>Becher PM, Savarese G, Benson L, Dahlström U, ... Pitt B, Lund LH</i><br /><b>Aims</b><br />The SOLOIST-WHF trial demonstrated efficacy of sotagliflozin in patients with type 2 diabetes mellitus (T2DM) and recent worsening heart failure (HF) regardless of ejection fraction (EF). Selection criteria in trials may limit their generalizability. Therefore, we aimed to investigate eligibility for sotagliflozin based on the SOLOIST-WHF criteria in a real-world HF population.<br /><b>Methods and results</b><br />SOLOIST-WHF criteria were applied to patients stabilized after HF hospitalization in the Swedish HF Registry according to 1) literal scenario (all inclusion/exclusion criteria) or 2) pragmatic scenario (only criteria likely to influence treatment decisions). Of 5453 inpatients with T2DM and recent worsening HF, 51.4% had reduced EF (HFrEF), 19.1% mildly reduced (HFmrEF), and 29.5% preserved EF (HFpEF). Eligibility (literal) was: 27.2% (32.4% in HFrEF, 24.7% in HFmrEF, 19.7% in HFpEF) and eligibility (pragmatic) was 62.8% (69.1%, 60.3%, 53.4%, respectively). In the literal scenario, criteria limiting eligibility were HF duration < 3 months, eGFR <30 ml/min/1.73m2, age > 85 years, acute coronary syndrome < 3 months, and insufficiently high N-terminal pro-B-type natriuretic peptide levels. Eligible vs. non-eligible patients had more severe HF, higher cardiovascular (CV) comorbidity burden, higher use of HF treatments, and higher event rates (all-cause death 30.8 vs. 27.2 per 100 patient-years, CV death 19.1 vs. 16.6, and HF hospitalization 36.7 vs. 24.0).<br /><b>Conclusion</b><br />In this large, real-world HF cohort with T2DM, ∼1/3 of patients were eligible for sotagliflozin in the literal and ∼2/3 of patients in the pragmatic scenario. Eligible patients had more severe HF and higher event rates, in particular CV and HF events.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Pharmacother: 30 Jan 2023; epub ahead of print</small></div>
Becher PM, Savarese G, Benson L, Dahlström U, ... Pitt B, Lund LH
Eur Heart J Cardiovasc Pharmacother: 30 Jan 2023; epub ahead of print | PMID: 36718512
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<div><h4>Beyond exercise oscillatory ventilations: the prognostic impact of loop gain in heart failure.</h4><i>Cunha GJL, Maltês S, Rocha BML, Nina D, ... Mendes M, Agostoni P</i><br /><AbstractText>Exercise oscillatory ventilation (EOV) is a strong prognostic marker in patients with heart failure (HF) and left ventricular (LV) dysfunction. This phenomenon can be explained through a single quantitative measurement of ventilatory instability, the loop gain. Therefore, we aimed to evaluate whether loop gain could be a better tool than subjective EOV evaluation to identify HF patients with a higher risk of major cardiovascular complications. This was a single-center retrospective study that included patients with left ventricular ejection fraction (LVEF) ≤ 50% consecutively referred for cardiopulmonary exercise testing (CPET) from 2016-2020. Loop gain was measured through computational evaluation of the minute ventilation graph. Of the 250 patients included, the 66 that presented EOV also had higher values of loop gain, when compared to patients without EOV. Those with both EOV and higher loop gain had more severe HF, with higher NT-proBNP and VE/VCO2 slope as well as lower peak VO2 and LVEF. On multivariable analysis, loop gain was strongly correlated with the composite endpoint of cardiovascular death, urgent heart transplantation, urgent left ventricular assist device implantation or HF hospitalization, even after correcting for peak VO2, LVEF, VE/VCO2 slope and NT-proBNP. Presence of EOV was not prognostically significant in this analysis. Loop gain is an objective parameter that quantifies ventilatory instability and showed to have a strong prognostic value in a cohort of patients with HF and LVEF ≤ 50%, outperforming the classification of EOV.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur J Prev Cardiol: 27 Jan 2023; epub ahead of print</small></div>
Cunha GJL, Maltês S, Rocha BML, Nina D, ... Mendes M, Agostoni P
Eur J Prev Cardiol: 27 Jan 2023; epub ahead of print | PMID: 36707994
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<div><h4>Heart failure classification based on resting ejection fraction does not display a unique exercise response pattern.</h4><i>Wernhart S, Papathanasiou M, Rassaf T, Luedike P</i><br /><b>Background</b><br />Heart failure with preserved (HFpEF), mildly reduced (HFmrEF) and reduced (HFrEF) ejection fraction (EF) remains a controversial categorization. Whether these three categories reflect a distinct pattern of exercise limitation in cardiopulmonary exercise testing (CPET) needs to be investigated. We aimed to analyze whether CPET variables differ between all heart failure categories (HF).<br /><b>Methods</b><br />We analyzed CPET variables of stable HFpEF (n = 123), HFmrEF (n = 31), and HFrEF (n = 153; 74 patients with and 79 patients without left ventricular assist device, LVAD) patients. The association between HF and peak oxygen consumption (VO<sub>2peak</sub>) was used as a primary outcome, while the association between HF, oxygen uptake efficiency slope (OUES), and increase of O<sub>2</sub> pulse (ΔO<sub>2</sub> pulse) were analyzed as secondary outcomes.<br /><b>Results</b><br />VO<sub>2peak</sub> displayed a consistent decline across all HF categories (19.8 ml ± 6.2/kg/min vs. 17.5 ± 7.9 ml/kg/min vs. 13.7 ± 4.0 ml/kg/min, p < 0.001). OUES only showed differences between HFpEF and HFrEF (1.8 ± 0.6 vs. 1.4 ± 0.5, p < 0.001) as well as HFmrEF and HFrEF (1.9 ± 0.9 vs. 1.4 ± 0.5, p = 0.004). ΔO<sub>2</sub> pulse differed between HFpEF and HFrEF (7.7 ± 3.5 ml/beat/kg*100 vs. 5.5 ± 3.0 ml/beat/kg*100, p < 0.001) as well as HFpEF and HFmrEF (7.7 ± 3.5 ml/beat/kg*100 vs. 6.3 ± 4.1 ml/beat/kg*100, p = 0.049). Outcome variables did not differ between HFrEF with and without LVAD support (VO<sub>2peak</sub>: p = 0.364, OUES: p = 0.129, ΔO<sub>2</sub> pulse: p = 0.564).<br /><b>Conclusions</b><br />HF did not display a distinct CPET profile. Thus, EF-based categorization does not entirely reflect exercise limitations. CPET variables could contribute to better characterize HF phenotypes.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 27 Jan 2023; epub ahead of print</small></div>
Wernhart S, Papathanasiou M, Rassaf T, Luedike P
Int J Cardiol: 27 Jan 2023; epub ahead of print | PMID: 36716970
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<div><h4>The importance of re-evaluating the risk score in heart failure patients: An analysis from the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score database.</h4><i>Pezzuto B, Piepoli M, Galotta A, Sciomer S, ... Sinagra G, Agostoni P</i><br /><b>Background</b><br />The role of risk scores in heart failure (HF) management has been highlighted by international guidelines. In contrast with HF, which is intrinsically a dynamic and unstable syndrome, all its prognostic studies have been based on a single evaluation. We investigated whether time-related changes of a well-recognized risk score, the MECKI score, added prognostic value. MECKI score is based on peak VO<sub>2</sub>, VE/VCO<sub>2</sub> slope, Na<sup>+</sup>, LVEF, MDRD and Hb.<br /><b>Methods</b><br />A multi-centre retrospective study was conducted involving 660 patients who performed MECKI re-evaluation at least 6 months apart. Based on the difference between II and I evaluation of MECKI values (MECKI II - MECKI I = ∆ MECKI) the study population was divided in 2 groups: those presenting a score reduction (∆ MECKI <0, i.e. clinical improvement), vs. patients presenting an increase (∆ MECKI >0, clinical deterioration).<br /><b>Results</b><br />The prognostic value of MECKI score is confirmed also when re-assessed during follow-up. The group with improved MECKI (366 patients) showed a better prognosis compared to patients with worsened MECKI (294 patients) (p < 0.0001). At 1st evaluation, the two groups differentiated by LVEF, V<sub>E</sub>/VCO<sub>2</sub> slope and blood Na<sup>+</sup> concentration, while at 2nd evaluation they differentiated in all 6 parameters considered in the score. The patients who improved MECKI score, improved in all components of the score but hemoglobin, while patients who worsened the score, worsened all parameters.<br /><b>Conclusions</b><br />This study shows that re-assessment of MECKI score identifies HF subjects at higher risk and that score improvement or deterioration regards several MECKI score generating parameters confirming the holistic background of HF.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 27 Jan 2023; epub ahead of print</small></div>
Pezzuto B, Piepoli M, Galotta A, Sciomer S, ... Sinagra G, Agostoni P
Int J Cardiol: 27 Jan 2023; epub ahead of print | PMID: 36716972
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<div><h4>Cardiac Resynchronization Therapy Improves Outcomes in Patients With Intraventricular Conduction Delay But Not Right Bundle Branch Block: A Patient-Level Meta-Analysis of Randomized Controlled Trials.</h4><i>Friedman DJ, Al-Khatib SM, Dalgaard F, Fudim M, ... Inoue LYT, Sanders GD</i><br /><b>Background</b><br />Benefit from cardiac resynchronization therapy (CRT) varies by QRS characteristics; individual randomized trials are underpowered to assess benefit for relatively small subgroups.<br /><b>Methods</b><br />The authors analyzed patient-level data from pivotal CRT trials (MIRACLE [Multicenter InSync Randomized Clinical Evaluation], MIRACLE-ICD [Multicenter InSync ICD Randomized Clinical Evaluation], MIRACLE-ICD II [Multicenter InSync ICD Randomized Clinical Evaluation II], REVERSE [Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction], RAFT [Resynchronization-Defibrillation for Ambulatory Heart Failure], BLOCK-HF [Biventricular Versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block], COMPANION [Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure], and MADIT-CRT [Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy]) using Bayesian Hierarchical Weibull survival regression models to assess CRT benefit by QRS morphology (left bundle branch block [LBBB], n=4549; right bundle branch block [RBBB], n=691; and intraventricular conduction delay [IVCD], n=1024) and duration (with 150-ms partition). The continuous relationship between QRS duration and CRT benefit was also examined within subgroups defined by QRS morphology. The primary end point was time to heart failure hospitalization (HFH) or death; a secondary end point was time to all-cause death.<br /><b>Results</b><br />Of 6264 patients included, 25% were women, the median age was 66 [interquartile range, 58 to 73] years, and 61% received CRT (with or without an implantable cardioverter defibrillator). CRT was associated with an overall lower risk of HFH or death (hazard ratio [HR], 0.73 [credible interval (CrI), 0.65 to 0.84]), and in subgroups of patients with QRS ≥150 ms and either LBBB (HR, 0.56 [CrI, 0.48 to 0.66]) or IVCD (HR, 0.59 [CrI, 0.39 to 0.89]), but not RBBB (HR 0.97 [CrI, 0.68 to 1.34]; <i>P</i><sub>interaction</sub> <0.001). No significant association for CRT with HFH or death was observed when QRS was <150 ms (regardless of QRS morphology) or in the presence of RBBB. Similar relationships were observed for all-cause death.<br /><b>Conclusions</b><br />CRT is associated with reduced HFH or death in patients with QRS ≥150 ms and LBBB or IVCD, but not for those with RBBB. Aggregating RBBB and IVCD into a single \"non-LBBB\" category when selecting patients for CRT should be reconsidered.<br /><b>Registration</b><br />URL: https://www.<br /><b>Clinicaltrials</b><br />gov; Unique identifiers: NCT00271154, NCT00251251, NCT00267098, and NCT00180271.<br /><br /><br /><br /><small>Circulation: 26 Jan 2023; epub ahead of print</small></div>
Friedman DJ, Al-Khatib SM, Dalgaard F, Fudim M, ... Inoue LYT, Sanders GD
Circulation: 26 Jan 2023; epub ahead of print | PMID: 36700426
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<div><h4>Improvement in Renal Function During the Treatment of Acute Decompensated Heart Failure: Relationship With Markers of Renal Tubular Injury and Prognostic Importance.</h4><i>Natov PS, Ivey-Miranda JB, Cox ZL, Moreno-Villagomez J, ... Rao VS, Testani JM</i><br /><b>Background</b><br />Improvement in renal function (IRF) in acute decompensated heart failure is associated with adverse outcomes. The mechanisms driving this paradox remain undefined.<br /><b>Methods</b><br />Using the ROSE-AHF study (Renal Optimization Strategies Evaluation-Acute Heart Failure), 277 patients were grouped according to renal function, with IRF defined by a ≥20% increase (N=75), worsening renal function by a ≥20% decline (N=53), and stable renal function (SRF) by a <20% change (N=149) in estimated glomerular filtration rate between baseline and 72 hours. Three well-validated renal tubular injury markers, NGAL (neutrophil gelatinase-associated lipocalin), NAG (N-acetyl-β-d-glucosaminidase), and KIM-1 (kidney injury molecule 1), were evaluated at baseline and 72 hours. Patients were also classified by the pattern of change in these markers.<br /><b>Results</b><br />Patients with IRF had the lowest admission estimated glomerular filtration rate (IRF, 37 [28 to 51] mL/min per 1.73 m<sup>2</sup>; worsening renal function, 43 [35 to 55] mL/min per 1.73 m<sup>2</sup>; and SRF, 43 [32 to 55] mL/min per 1.73 m<sup>2</sup>; <i>P</i><sub>trend</sub>=0.032) but greater cumulative urine output (IRF, 8780 [7025 to 11 208] mL; worsening renal function, 7860 [5555 to 9765] mL; and SRF, 8150 [6325 to 10 456] mL; <i>P</i><sub>trend</sub>=0.024) and weight loss (IRF, -9.0 [-12.4 to -5.3] lb; worsening renal function, -5.1 [-8.1 to -1.3] lb; and SRF, -7.1 [-11.9 to -3.2] lb; <i>P</i><sub>trend</sub><0.001) despite similar diuretic doses (<i>P</i><sub>trend</sub>=0.16). There were no differences in the relative change in NGAL, NAG, or KIM-1 between renal function groups (<i>P</i><sub>trend</sub>>0.19 for all). Patients with IRF had worse survival than patients with SRF (27% versus 54%; hazard ratio, 1.98 [1.10-3.58]; <i>P</i>=0.024).<br /><b>Conclusions</b><br />IRF during decongestive therapy for acute decompensated heart failure was not associated with improved markers of renal tubular injury and was associated with worsened survival, likely driven by the presence of greater underlying cardiorenal dysfunction and more severe congestion.<br /><br /><br /><br /><small>Circ Heart Fail: 26 Jan 2023:e009776; epub ahead of print</small></div>
Natov PS, Ivey-Miranda JB, Cox ZL, Moreno-Villagomez J, ... Rao VS, Testani JM
Circ Heart Fail: 26 Jan 2023:e009776; epub ahead of print | PMID: 36700431
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<div><h4>A comprehensive meta-analysis comparing radiofrequency ablation versus pharmacological therapy for the treatment of atrial fibrillation in patients with heart failure.</h4><i>Casula M, Pignalosa L, Quilico F, Scajola LV, Rordorf R</i><br /><b>Background</b><br />Atrial fibrillation (AF) and heart failure (HF) are both associated with worse prognosis and often coexist in the same patients. Whether catheter ablation (CA) is superior to pharmacological therapy in reducing major clinical endpoints in patients with AF and HF is still unsettled.<br /><b>Objective</b><br />To conduct a comprehensive meta-analysis comparing CA with medical therapy (MT) in this population.<br /><b>Methods</b><br />We systematically searched for randomized and observational studies comparing clinical outcomes between patients with AF and HF treated with CA or MT. The studied outcomes were mortality, hospitalization, left ventricle ejection fraction (LVEF) and 6-min walking test (6MWT) improvement.<br /><b>Results</b><br />A total of 12 studies counting 41,377 patients (3611 treated with CA and 37,766 with MT) were included in the analysis. The random-effect model revealed a clear trend in favor of CA in reducing unexpected HF hospitalization (RR 0.72; 95%CI 0.51-1.00; P = 0.05), all-cause death (RR 0.77; 95%CI 0.59-1.01; P = 0.06), all-cause hospitalization (RR 0.84; 95%CI 0.68-1.03; P = 0.09), and the composite of HF hospitalization and death (RR 0.77; 95%CI 0.58-1.02; P = 0.07), compared with MT. Patients treated with CA experienced a better improvement in LVEF (mean difference 6.17; 95%CI 2.98-9.37; P = 0.0002) and 6MWT (mean difference 13.70; 95%CI 3.95-23.45; P = 0.006). When the analysis was limited to randomized controlled trial, CA was found to significantly reduce all-cause death (RR 0.68; 95%CI 0.54-0.86; P = 0.001).<br /><b>Conclusion</b><br />As compared to MT, CA is associated with a better improvement in functional capacity and LVEF, and with a reduction in major clinical endpoints in patients with HF and AF.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 26 Jan 2023; epub ahead of print</small></div>
Casula M, Pignalosa L, Quilico F, Scajola LV, Rordorf R
Int J Cardiol: 26 Jan 2023; epub ahead of print | PMID: 36709925
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<div><h4>Hemodynamic Profiling and Prognosis in Cardiac Amyloidosis.</h4><i>Martens P, Bhattacharya S, Longinow J, Ives L, ... Hanna M, Tang WHW</i><br /><b>Background</b><br />Little information is available on the prognostic relevance of cardiac hemodynamic cutoffs in cardiac amyloidosis (CA) and its subtypes.<br /><b>Methods</b><br />Consecutive patients diagnose with light chain-CA or transthyretin CA undergoing right heart catheterization were analyzed. Prognostic relevance of classic hemodynamic cutoffs of cardiac index (CI <2.2 L/min per m<sup>2</sup>), pulmonary capillary wedge pressure (>18 mm Hg), right atrial pressure (>8 mm Hg), and mean pulmonary artery pressure (≥25 mm Hg or pulmonary hypertension) with the combined end point of cardiac transplant/left ventricular assist device and death and heart failure admissions separately was assessed.<br /><b>Results</b><br />A total of 469 CA patients underwent right heart catheterization (light chain CA=42% and transthyretin CA=52%) of whom 69%, 64%, and 79% had elevated right atrial pressure, pulmonary capillary wedge pressure, and pulmonary hypertension, respectively. The classic hemodynamic cutoffs for right atrial pressure (hazard ratio, 1.26 [0.98-1.62]) and mean pulmonary artery pressure (hazard ratio, 1.28 [0.96-1.71]) did not identify patients at higher risk for adverse outcome; however, cutoffs of 14 mm Hg for right atrial pressure (hazard ratio, 1.59 [1.26-2.00]) and 35 mm Hg for mean pulmonary artery pressure (hazard ratio, 1.30 [1.01-1.66]) performed better to detect worse outcome (<i>P</i><0.05 for both). Reduced CI occurred in 55% of patients and was the strongest variable associated with the risk for cardiac transplant/left ventricular assist device and death, heart failure admissions, and reduced functional capacity. Reduced CI independently predicted risk on top of the Mayo-score in light chain CA and National Amyloid Center score in transthyretin CA (<i>P</i><0.05 for both). Patients with light chain CA had higher pulmonary capillary wedge pressure and lower stroke volume index but maintained CI through a higher heart rate.<br /><b>Conclusions</b><br />Hemodynamic variables are grossly abnormal in CA, but elevated filling pressures are prognostic at significantly higher threshold values than classic cutoff values. CI is the hemodynamic variable most strongly associated with outcome and functionality in CA.<br /><br /><br /><br /><small>Circ Heart Fail: 25 Jan 2023:e010078; epub ahead of print</small></div>
Martens P, Bhattacharya S, Longinow J, Ives L, ... Hanna M, Tang WHW
Circ Heart Fail: 25 Jan 2023:e010078; epub ahead of print | PMID: 36695180
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<div><h4>Mechanical Dyssynchrony of Isolated Left and Right Ventricular Human Myocardium in End-Stage Heart Failure.</h4><i>Mashali MA, Saad NS, Peczkowski KK, Fanning T, ... Mokadam NA, Janssen PML</i><br /><b>Background</b><br />The left and right ventricles of the human heart differ in embryology, shape, thickness, and function. Ventricular dyssynchrony often occurs in cases of heart failure. Our objectives were to assess whether differences in contractile properties exist between the left and right ventricles and to evaluate signs of left/right ventricular mechanical synchrony in isolated healthy and diseased human myocardium.<br /><b>Methods</b><br />Myocardial left and right ventricular trabeculae were dissected from nonfailing and end-stage failing human hearts. Baseline contractile force and contraction/relaxation kinetics of the left ventricle were compared to those of the right ventricle in the nonfailing group (n=41) and in the failing group (n=29). Correlation analysis was performed to assess the mechanical synchrony between left and right ventricular myocardium isolated from the same heart, in nonfailing (n=41) and failing hearts (n=29).<br /><b>Results</b><br />The failing right ventricular myocardium showed significantly higher developed force (Fdev; <i>P</i>=0.001; d=0.98), prolonged time to peak (<i>P</i><0.001; d=1.14), and higher rate of force development (<i>P</i>=0.002; d=0.89) and force decline (<i>P</i>=0.003; d=0.82) compared to corresponding left ventricular myocardium. In healthy myocardium, a strong positive relationship was present between the left and right ventricles in time to peak (r=0.58, <i>P</i><0.001) and maximal kinetic rate of contraction (r=0.63, <i>P</i><0.001). These coefficients were much weaker, often nearly absent, in failing myocardium.<br /><b>Conclusions</b><br />At the level of isolated cardiac trabeculae, contractile performance, specifically of contractile kinetics, is correlated in the nonfailing myocardium between the left and right ventricles\' but this correlation is significantly weaker, or even absent, in end-stage heart failure, suggesting an interventricular mechanical dyssynchrony.<br /><br /><br /><br /><small>Circ Heart Fail: 25 Jan 2023:e009871; epub ahead of print</small></div>
Mashali MA, Saad NS, Peczkowski KK, Fanning T, ... Mokadam NA, Janssen PML
Circ Heart Fail: 25 Jan 2023:e009871; epub ahead of print | PMID: 36695183
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<div><h4>Phenotyping of Elderly Patients With Heart Failure Focused on Noncardiac Conditions: A Latent Class Analysis From a Multicenter Registry of Patients Hospitalized With Heart Failure.</h4><i>Nakamaru R, Shiraishi Y, Niimi N, Kohno T, ... Kohsaka S, Yoshikawa T</i><br /><AbstractText><br /><b>Background:</b><br/>The burden of noncardiovascular conditions is becoming increasingly prevalent in patients with heart failure (HF). We aimed to identify novel phenogroups incorporating noncardiovascular conditions to facilitate understanding and risk stratification in elderly patients with HF. Methods and Results Data from a total of 1881 (61.2%) patients aged ≥65 years were extracted from a prospective multicenter registry of patients hospitalized for acute HF (N=3072). We constructed subgroups of patients with HF with preserved ejection fraction (HFpEF; N=826, 43.9%) and those with non-HFpEF (N=1055, 56.1%). Latent class analysis was performed in each subgroup using 17 variables focused on noncardiovascular conditions (including comorbidities, Clinical Frailty Scale, and Geriatric Nutritional Risk Index). The latent class analysis revealed 3 distinct clinical phenogroups in both HFpEF and non-HFpEF subgroups: (1) robust physical and nutritional status (Group 1: HFpEF, 41.2%; non-HFpEF, 46.0%); (2) multimorbid patients with renal impairment (Group 2: HFpEF, 40.8%; non-HFpEF, 41.9%); and (3) malnourished patients (Group 3: HFpEF, 18.0%; non-HFpEF, 12.1%). After multivariable adjustment, compared with Group 1, patients in Groups 2 and 3 had a higher risk for all-cause death over the 1-year postdischarge period (hazard ratio [HR], 2.79 [95% CI, 1.64-4.81] and HR, 2.73 [95% CI, 1.39-5.35] in HFpEF; HR, 1.96 [95% CI, 1.22-3.14] and HR, 2.97 [95% CI, 1.64-5.38] in non-HFpEF; respectively). <br /><b>Conclusions:</b><br/>In elderly patients with HF, the phenomapping focused on incorporating noncardiovascular conditions identified 3 phenogroups, each representing distinct clinical outcomes, and the discrimination pattern was similar for both patients with HFpEF and non-HFpEF. This classification provides novel risk stratification and may aid in clinical decision making.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e027689; epub ahead of print</small></div>
Nakamaru R, Shiraishi Y, Niimi N, Kohno T, ... Kohsaka S, Yoshikawa T
J Am Heart Assoc: 25 Jan 2023:e027689; epub ahead of print | PMID: 36695300
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<div><h4>Association of Rurality With Risk of Heart Failure.</h4><i>Turecamo SE, Xu M, Dixon D, Powell-Wiley TM, ... Lipworth L, Roger VL</i><br /><b>Importance</b><br />Rural populations experience an increased burden of heart failure (HF) mortality compared with urban populations. Whether HF incidence is greater among rural individuals is less known. Additionally, the intersection between racial and rural health inequities is understudied.<br /><b>Objective</b><br />To determine whether rurality is associated with increased risk of HF, independent of cardiovascular (CV) disease and socioeconomic status (SES), and whether rurality-associated HF risk varies by race and sex.<br /><b>Design, setting, and participants</b><br />This prospective cohort study analyzed data for Black and White participants of the Southern Community Cohort Study (SCCS) without HF at enrollment who receive care via Centers for Medicare & Medicaid Services (CMS). The SCCS is a population-based cohort of low-income, underserved participants from 12 states across the southeastern United States. Participants were enrolled between 2002 and 2009 and followed up until December 31, 2016. Data were analyzed from October 2021 to November 2022.<br /><b>Exposures</b><br />Rurality as defined by Rural-Urban Commuting Area codes at the census-tract level.<br /><b>Main outcomes and measures</b><br />Heart failure was defined using diagnosis codes via CMS linkage through 2016. Incidence of HF was calculated by person-years of follow-up and age-standardized. Sequentially adjusted Cox proportional hazards regression models tested the association between rurality and incident HF.<br /><b>Results</b><br />Among 27 115 participants, the median (IQR) age was 54 years (47-65), 18 647 (68.8%) were Black, and 8468 (32.3%) were White; 5556 participants (20%) resided in rural areas. Over a median 13-year follow-up, age-adjusted HF incidence was 29.6 (95% CI, 28.9-30.5) per 1000 person-years for urban participants and 36.5 (95% CI, 34.9-38.3) per 1000 person-years for rural participants (P < .001). After adjustment for demographic information, CV risk factors, health behaviors, and SES, rural participants had a 19% greater risk of incident HF (hazard ratio [HR], 1.19; 95% CI, 1.13-1.26) compared with their urban counterparts. The rurality-associated risk of HF varied across race and sex and was greatest among Black men (HR, 1.34; 95% CI, 1.19-1.51), followed by White women (HR, 1.22; 95% CI, 1.07-1.39) and Black women (HR, 1.18; 95% CI, 1.08-1.28). Among White men, rurality was not associated with greater risk of incident HF (HR, 0.97; 95% CI, 0.81-1.16).<br /><br /><b>Conclusions:</b><br/>and relevance</b><br />Among predominantly low-income individuals in the southeastern United States, rurality was associated with an increased risk of HF among women and Black men, which persisted after adjustment for CV risk factors and SES. This inequity points to a need for additional emphasis on primary prevention of HF among rural populations.<br /><br /><br /><br /><small>JAMA Cardiol: 25 Jan 2023; epub ahead of print</small></div>
Turecamo SE, Xu M, Dixon D, Powell-Wiley TM, ... Lipworth L, Roger VL
JAMA Cardiol: 25 Jan 2023; epub ahead of print | PMID: 36696094
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<div><h4>Influence of Social Determinants of Health on Heart Failure Outcomes: A Systematic Review.</h4><i>Enard KR, Coleman AM, Yakubu RA, Butcher BC, Tao D, Hauptman PJ</i><br /><AbstractText><br /><b>Background:</b><br/>Prior research suggests an association between clinical outcomes in heart failure (HF) and social determinants of health (SDoH). Because providers should identify and address SDoH in care delivery, we evaluated how SDoH have been defined, measured, and evaluated in studies that examine HF outcomes. Methods and Results Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, databases were searched for observational or interventional studies published between 2009 and 2021 that assessed the influence of SDoH on outcomes. Selected articles were assessed for quality using a validated rating scheme. We identified 1373 unique articles for screening; 104 were selected for full-text review, and 59 met the inclusion criteria, including retrospective and prospective cohort, cross-sectional, and intervention studies. The majority examined readmissions and hospitalizations (k=33), mortality or survival (k=29), and success of medical devices and transplantation (k=8). SDoH examined most commonly included race, ethnicity, age, sex, socioeconomic status, and education or health literacy. Studies used a range of 1 to 9 SDoH as primary independent variables and 0 to 7 SDoH as controls. Multiple data sources were employed and frequently were electronic medical records linked with national surveys and disease registries. The effects of SDoH on HF outcomes were inconsistent because of the heterogeneity of data sources and SDoH constructs. <br /><b>Conclusions:</b><br/>Our systematic review reveals shortcomings in measurement and deployment of SDoH variables in HF care. Validated measures need to be prospectively and intentionally collected to facilitate appropriate analysis, reporting, and replication of data across studies and inform the design of appropriate, evidence-based interventions that can ameliorate significant HF morbidity and societal costs.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 25 Jan 2023:e026590; epub ahead of print</small></div>
Enard KR, Coleman AM, Yakubu RA, Butcher BC, Tao D, Hauptman PJ
J Am Heart Assoc: 25 Jan 2023:e026590; epub ahead of print | PMID: 36695317
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<div><h4>Right ventricular free wall strain and effect of defibrillator implantation in patients with non-ischemic systolic heart failure.</h4><i>Elming MB, Jensen DH, Winsløw UC, Risum N, ... Køber L, Thune JJ</i><br /><b>Aims</b><br />Patients with non-ischemic systolic heart failure have an increased risk of malignant ventricular arrhythmias and sudden cardiovascular death. Since the risk is less pronounced than for patients with ischemic cause of heart failure more discriminating tools are needed to identify patients most likely to benefit from implantable cardioverter-defibrillator (ICD) implantation. Right ventricular (RV) dysfunction is associated with a worse prognosis, but whether RV free wall strain (RV-FWS) measured with echocardiography can identify the patients most likely to benefit from ICD implantation is not known.<br /><b>Methods</b><br />In this extended follow-up analysis of the Danish Study to Assess the Efficacy of ICDs in Patients with Non-ischemic Systolic Heart Failure on Mortality (DANISH) trial, RV-FWS was measured with echocardiography in 445 patients prior to randomization. RV dysfunction was defined as RV-FWS > -20%. The primary endpoint was all-cause mortality.<br /><b>Results</b><br />Median RV-FWS was -18% (quartiles: -23% to -14%), and RV dysfunction was measured in 255 (57%) patients. During a median follow-up of 5.7 years, 170 (38%) patients died. There was a statistically significant interaction between RV dysfunction and the effect of ICD implantation (p=0.003), also after adjusting for known cardiovascular risk factors (p=0.01). ICD implantation significantly reduced all-cause mortality in patients with RV dysfunction, HR 0.54 (95% CI 0.36-0.80), p = 0.002, but not in patients with normal RV function, HR 1.34 (95% CI 0.84-2.12), p = 0.22.<br /><b>Conclusions</b><br />In patients with non-ischemic systolic heart failure, RV dysfunction on echocardiography was associated with greater effect of ICD implantation and could be used to select patients with benefit from ICD treatment.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 25 Jan 2023; epub ahead of print</small></div>
Elming MB, Jensen DH, Winsløw UC, Risum N, ... Køber L, Thune JJ
J Card Fail: 25 Jan 2023; epub ahead of print | PMID: 36708755
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<div><h4>Albuminuria and Heart Failure: JACC State-of-the-Art Review.</h4><i>Khan MS, Shahid I, Anker SD, Fonarow GC, ... Bakris GL, Butler J</i><br /><AbstractText>Although chronic kidney disease is characterized by low glomerular filtration rate (GFR) or albuminuria, estimated GFR (eGFR) is more widely utilized as a marker of risk profile in cardiovascular diseases, including heart failure (HF). The presence and magnitude of albuminuria confers a strong prognostic association in forecasting risk of incident HF as well as its progression, irrespective of eGFR. Despite the high prevalence of albuminuria in HF, whether it adds incremental prognostic information in clinical practice and serves as an independent risk marker, and whether there are any therapeutic implications of assessing albuminuria in patients with HF is less well-established. In this narrative review, we assess the potential role of albuminuria in risk profiling for development and progression of HF, strengths and limitations of utilizing albuminuria as a risk marker, its ability to serve in HF risk prediction models, and the implications of adopting albuminuria as an effective parameter in cardiovascular trials and practice.</AbstractText><br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 24 Jan 2023; 81:270-282</small></div>
Khan MS, Shahid I, Anker SD, Fonarow GC, ... Bakris GL, Butler J
J Am Coll Cardiol: 24 Jan 2023; 81:270-282 | PMID: 36653095
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<div><h4>Incremental diagnostic value of post-exercise lung congestion in heart failure with preserved ejection fraction.</h4><i>Kagami K, Obokata M, Harada T, Sorimachi H, ... Adachi T, Ishii H</i><br /><b>Aims</b><br />Lung ultrasound (LUS) may unmask occult heart failure with preserved ejection fraction (HFpEF) by demonstrating an increase in extravascular lung water (EVLW) during exercise. Here, we sought to examine the dynamic changes in ultrasound B-lines during exercise to identify the optimal timeframe for HFpEF diagnosis.<br /><b>Methods and results</b><br />Patients with HFpEF (n = 134) and those without HF (controls, n = 121) underwent a combination of exercise stress echocardiography and LUS with simultaneous expired gas analysis to identify exercise EVLW. Exercise EVLW was defined by B-lines that were newly developed or increased during exercise. The E/e\' ratio peaked during maximal exercise and immediately decreased during the recovery period in patients with HFpEF. Exercise EVLW was most prominent during the recovery period in patients with HFpEF, while its prevalence did not increase from peak exercise to the recovery period in controls. Exercise EVLW was associated with a higher E/e\' ratio and pulmonary artery pressure, lower right ventricular systolic function, and elevated minute ventilation to carbon dioxide production (VE vs. VCO2) slope during peak exercise. Increases in B-lines from rest to the recovery period provided an incremental diagnostic value to identify HFpEF over the H2FPEF score and resting left atrial reservoir strain.<br /><b>Conclusion</b><br />Exercise EVLW was most prominent early during the recovery period; this may be the optimal timeframe for imaging ultrasound B-lines. Exercise stress echocardiography with assessments of recovery EVLW may enhance the diagnosis of HFpEF.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J Cardiovasc Imaging: 24 Jan 2023; epub ahead of print</small></div>
Kagami K, Obokata M, Harada T, Sorimachi H, ... Adachi T, Ishii H
Eur Heart J Cardiovasc Imaging: 24 Jan 2023; epub ahead of print | PMID: 36691846
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<div><h4>Temporal trends in the incidence of malignancy in heart failure: a nationwide Danish study.</h4><i>Bruhn J, Malmborg M, Garred CH, Ravn P, ... Kober L, Schou M</i><br /><b>Aims</b><br />Cancer and heart failure (HF) share risk factors, pathophysiological mechanisms, and possibly genetics. Improved HF survival may increase the risk of cancer due to a competing risk. Whether the incidence of cancer has increased over time in patients with HF as survival has improved is unclear. Therefore, temporal trends of new onset cancer in HF patients between 1997 and 2016 were investigated.<br /><b>Methods and results</b><br />Using Danish nationwide registers, 103 711 individuals alive, free of cancer, and aged 30-80 years 1 year after HF diagnosis (index date) were included between 1 January 1997 and 31 December 2016. A five-year incidence rate of cancer for each year after index date was calculated. The median age and proportion of women at the index date decreased with advancing calendar time [1997-2001: 70.3 interquartile range (Q1-Q3 62.5-75.7), 60.9% men; 2012-16: 67.6 (59.2-73.8), 67.5% men]. The five-year incidence rate of cancer was 20.9 and 20.2 per 1,000 person-years in 1997 and 2016, respectively. In a multivariable Cox regression model, the hazard rates between index years 1997 (reference) and 2016 were not significantly different [hazard ratio 1.09 (0.97-1.23)]. The five-year absolute risk of cancer did not change with advancing calendar year, going from 9.0% (1997-2001) to 9.0% (2012-16). Five-year cumulative incidence of survival for HF patients increased with advancing calendar year, going from 55.9% (1997-2001) to 74.3% (2012-2016).<br /><b>Conclusion</b><br />Although cancer rates during 1997-2016 have remained stable within 1-6 years after the HF diagnosis, long-term survival following a HF diagnosis has increased significantly.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 24 Jan 2023; epub ahead of print</small></div>
Bruhn J, Malmborg M, Garred CH, Ravn P, ... Kober L, Schou M
Eur Heart J: 24 Jan 2023; epub ahead of print | PMID: 36691953
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<div><h4>Major cardiovascular events and subsequent risk of kidney failure with replacement therapy: a CKD Prognosis Consortium study.</h4><i>Mark PB, Carrero JJ, Matsushita K, Sang Y, ... Visseren FLJ, Stengel B</i><br /><b>Aims</b><br />Chronic kidney disease (CKD) increases risk of cardiovascular disease (CVD). Less is known about how CVD associates with future risk of kidney failure with replacement therapy (KFRT).<br /><b>Methods and results</b><br />The study included 25 903 761 individuals from the CKD Prognosis Consortium with known baseline estimated glomerular filtration rate (eGFR) and evaluated the impact of prevalent and incident coronary heart disease (CHD), stroke, heart failure (HF), and atrial fibrillation (AF) events as time-varying exposures on KFRT outcomes. Mean age was 53 (standard deviation 17) years and mean eGFR was 89 mL/min/1.73 m2, 15% had diabetes and 8.4% had urinary albumin-to-creatinine ratio (ACR) available (median 13 mg/g); 9.5% had prevalent CHD, 3.2% prior stroke, 3.3% HF, and 4.4% prior AF. During follow-up, there were 269 142 CHD, 311 021 stroke, 712 556 HF, and 605 596 AF incident events and 101 044 (0.4%) patients experienced KFRT. Both prevalent and incident CVD were associated with subsequent KFRT with adjusted hazard ratios (HRs) of 3.1 [95% confidence interval (CI): 2.9-3.3], 2.0 (1.9-2.1), 4.5 (4.2-4.9), 2.8 (2.7-3.1) after incident CHD, stroke, HF and AF, respectively. HRs were highest in first 3 months post-CVD incidence declining to baseline after 3 years. Incident HF hospitalizations showed the strongest association with KFRT [HR 46 (95% CI: 43-50) within 3 months] after adjustment for other CVD subtype incidence.<br /><b>Conclusion</b><br />Incident CVD events strongly and independently associate with future KFRT risk, most notably after HF, then CHD, stroke, and AF. Optimal strategies for addressing the dramatic risk of KFRT following CVD events are needed.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 24 Jan 2023; epub ahead of print</small></div>
Mark PB, Carrero JJ, Matsushita K, Sang Y, ... Visseren FLJ, Stengel B
Eur Heart J: 24 Jan 2023; epub ahead of print | PMID: 36691956
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<div><h4>In which patients with heart failure should ablation of atrial fibrillation not be performed?</h4><i>Hachiya H</i><br /><AbstractText>Catheter ablation of atrial fibrillation (AF) in patients with heart failure associated with a reduced EF (HFrEF) was associated with a significantly lower rate of a composite endpoint of death from any cause or hospitalization for worsening heart failure (HF) than medical therapy in the CASTLE-AF trial. In patients with HF and also with a preserved EF (HFpEF), AF is known to be associated with increased mortality. Although the particular benefit in patients with an EF >35% may suggest the need for prospective randomized control trial data in patients with HF to assess the role of ablation as a first-line therapy as Sessions AJ, et al. stated, we believe at present that 1) whether there is structural heart disease detected by cardiac images and 2) whether the left atrial voltage is generally low, should be assessed \"before ablation\" in each patient with HF to achieve a successful ablation. This article is protected by copyright. All rights reserved.</AbstractText><br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>J Cardiovasc Electrophysiol: 24 Jan 2023; epub ahead of print</small></div>
Hachiya H
J Cardiovasc Electrophysiol: 24 Jan 2023; epub ahead of print | PMID: 36691910
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<div><h4>Effect of Patisiran on Stroke Volume in Hereditary Transthyretin-Mediated Amyloidosis: Insights from Pressure-Volume Analysis of the APOLLO Study.</h4><i>Rosenblum HR, Griffin JM, Minamisawa M, Prasad N, ... Burkhoff MDD, Maurer MS</i><br /><b>Aims</b><br />Transthyretin-mediated (ATTR) amyloidosis is caused by deposition of transthyretin protein fibrils in the heart, nerves, and other organs. Patisiran, an RNA interference (RNAi) therapeutic that inhibits hepatic synthesis of transthyretin, was approved for the treatment of hereditary ATTR amyloidosis with polyneuropathy based on the phase III APOLLO study. We use left ventricular (LV) stroke volume (SV) to quantify LV function overtime and non-invasive pressure-volume techniques to delineate the effects of patisiran on LV mechanics in the prespecified cardiac subpopulation of the APOLLO study.<br /><b>Methods and results</b><br />LV SV was assessed by transthoracic echocardiography at baseline, and 9 and 18 months of therapy. To determine mechanisms underlying changes in LV SV, non-invasive pressure-volume (PV) parameters, including the end-systolic pressure-volume relationship and end-diastolic pressure-volume relationship, were derived using single beat techniques. At baseline, the mean SV was 51 ± 14mL. At 9 months, the LS mean change in SV was -0.3 ± 1.2 mL for patisiran and -5.4 ± 1.9 mL for placebo (p=0.021). At 18 months, the LS mean change in SV was -1.7 ± 1.3mL for patisiran and -8.1 ± 2.3mL for placebo (p=0.016). Decline in LV SV was driven by diminished LV capacitance in placebo relative to patisiran.<br /><b>Conclusions</b><br />Patisiran may delay progression of LV chamber dysfunction starting at 9 months of therapy. These data elucidate the mechanisms by which transthyretin reducing therapies modulate progression of cardiac disease and need to be confirmed in ongoing phase III trials.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 24 Jan 2023; epub ahead of print</small></div>
Rosenblum HR, Griffin JM, Minamisawa M, Prasad N, ... Burkhoff MDD, Maurer MS
Eur J Heart Fail: 24 Jan 2023; epub ahead of print | PMID: 36693807
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<div><h4>Effect of flu vaccination on severity and outcome of heart failure decompensations.</h4><i>Miró Ò, Ivars N, Lopez-Ayala P, Gil V, ... Llorens P, (on behalf of the ICA-SEMES groupb)</i><br /><b>Objective</b><br />To investigate the relationship of seasonal flu vaccination with severity of decompensations and long-term outcomes of patients with heart failure (HF).<br /><b>Methods</b><br />We analyzed 6,147 consecutively enrolled decompensated HF patients who presented to 33 Spanish emergency departments (EDs) during January and February, 2018 and 2019, grouped according to seasonal flu vaccination status. Severity of HF decompensation was assessed with the MEESSI scale, need of hospitalization, and in-hospital all-cause mortality. Long-term outcomes analyzed were 90-day post-discharge adverse events and 90-day all-cause death. Associations between vaccination, HF decompensation severity, and long-term outcomes were explored by unadjusted and adjusted logistic and Cox regressions using 14 covariables that could act as potential confounders.<br /><b>Results</b><br />Overall median (IQR) age was 84 (IQR=77-89) years, 56% were women. Vaccinated patients (n=1,139, 19%) were older, with more comorbidities, and with worse baseline status assessed by NYHA class and Barthel index, than unvaccinated patients (n=5,008, 81%). Infection triggering decompensation was more frequent in vaccinated patients (50% versus 41%, p<0.001). In vaccinated and unvaccinated patients, high or very-high risk decompensation was seen in 21.9% and 21.1%, hospitalization occurred in 72.5% and 73.7%, in-hospital mortality was 7.4% and 7.0%, 90-day post-discharge adverse events were 57.4% and 53.2%, and 90-day mortality was 15.8% and 16.6%, respectively, with no significant differences between cohorts. After adjusting, vaccinated decompensated HF patients had a decreased odds for hospitalization (OR=0.823, 95%CI=0.709-0.955).<br /><b>Conclusion</b><br />In HF patients, seasonal flu vaccination is associated with less severe decompensations.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 24 Jan 2023; epub ahead of print</small></div>
Miró Ò, Ivars N, Lopez-Ayala P, Gil V, ... Llorens P, (on behalf of the ICA-SEMES groupb)
J Card Fail: 24 Jan 2023; epub ahead of print | PMID: 36706976
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<div><h4>Validity of International Classification of Diseases (ICD)-10 Diagnosis Codes for Identification of Acute Heart Failure Hospitalization and Heart Failure with Reduced Versus Preserved Ejection Fraction in a National Medicare Sample.</h4><i>Bates BA, Akhabue E, Nahass MM, Mukherjee A, ... Dave CV, Setoguchi S</i><br /><b>Background</b><br />Heart failure (HF) is a leading cause of hospitalization in older adults. Medicare data have been used to assess HF outcomes. However, the validity of ICD-10 diagnosis codes (used since 2015) to identify acute HF hospitalization or distinguish reduced (heart failure with reduced ejection fraction) versus preserved ejection fraction (HFpEF) is unknown in Medicare data.<br /><b>Methods</b><br />Using Medicare data (2015-2017), we randomly sampled 200 HF hospitalizations with ICD-10 diagnosis codes for HF in the first/second claim position in a 1:1:2 ratio for systolic HF (I50.2), diastolic HF (I50.3), and other HF (I50.X). The primary gold standards included recorded HF diagnosis by a treating physician for HF hospitalization, ejection fraction (EF)≤50 for heart failure with reduced ejection fraction, and EF>50 for HFpEF. If the quantitative EF was not present, then qualitative descriptions of EF were used for heart failure with reduced ejection fraction/HFpEF gold standards. Multiple secondary gold standards were also tested. Gold standard data were extracted from medical records using standardized forms and adjudicated by cardiology fellows/staff. We calculated positive predictive values with 95% CIs.<br /><b>Results</b><br />The 200-chart validation sample included 50 systolic, 50 diastolic, 47 combined dysfunction, and 53 unspecified HF patients. The positive predictive values of acute HF hospitalization was 98% [95% CI, 95-100] for first-position ICD-10 HF diagnosis and 66% [95% CI, 58-74] for first/second-position diagnosis. Quantitative EF was available for ≥80% of patients with systolic, diastolic, or combined dysfunction ICD-10 codes. The positive predictive value of systolic HF codes was 90% [95% CI, 82-98] for EFs≤50% and 72% [95% CI, 60-85] for EFs≤40%. The positive predictive value was 92% [95% CI, 85-100] for HFpEF for EFs>50%. The ICD-10 codes for combined or unspecified HF poorly predicted heart failure with reduced ejection fraction or HFpEF.<br /><b>Conclusions</b><br />ICD-10 principal diagnosis identified acute HF hospitalization with a high positive predictive value. Systolic and diastolic ICD-10 diagnoses reliably identified heart failure with reduced ejection fraction and HFpEF when EF 50% was used as the cutoff.<br /><br /><br /><br /><small>Circ Cardiovasc Qual Outcomes: 23 Jan 2023:e009078; epub ahead of print</small></div>
Bates BA, Akhabue E, Nahass MM, Mukherjee A, ... Dave CV, Setoguchi S
Circ Cardiovasc Qual Outcomes: 23 Jan 2023:e009078; epub ahead of print | PMID: 36688301
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<div><h4>Concomitant latent pulmonary vascular disease leads to impaired global cardiac performance in HFpEF.</h4><i>Schuster A, Schulz A, Lange T, Evertz R, ... Hasenfuß G, Backhaus SJ</i><br /><b>Aims</b><br />The REDUCE-LAP II trial demonstrated adverse outcomes after interatrial shunt device (IASD) placement in heart failure with preserved ejection fraction (HFpEF) attributed to latent pulmonary vascular disease (PVD). We hypothesized that exercise-stress cardiovascular magnetic resonance (CMR) imaging could provide non-invasive characterisation of cardiac and pulmonary physiology for improved patient selection.<br /><b>Methods and results</b><br />The HFpEF-Stress Trial prospectively enrolled 75 patients with exertional dyspnoea and diastolic dysfunction. Patients underwent rest and exercise-stress right heart catheterisation (RHC), echocardiography and CMR imaging. Pulmonary artery and capillary wedge pressures, cardiac index (CI) and vascular resistance (PVR) were calculated. Latent PVD was defined as increased PVR≥1.74 Wood-Units during exercise-stress. CMR assessed long axis strains (LAS) and filling volumes of all cardiac chambers. Right ventricular (RV) function was further quantified by stroke and peak flow volumes. Patients with latent PVD (n = 24) showed lower RV function (rest TAPSE, p = 0.010; stress RV LAS, p < 0.001) compared to patients without (n = 43). During exercise-stress, RV stroke and peak flow volumes (p < 0.001) were reduced and led to impaired left atrial (p = 0.040) and with a strong statistical trend to impaired ventricular (LV) filling (p = 0.098). This subsequently resulted in reduced LV-CI (p < 0.001) despite preserved LV systolic function (LV LAS p ≥ 0.255). The degree of RV dysfunction during exercise-stress best predicted latent PVD (RV peak flow, AUC rest 0.73 vs. stress 0.89, p = 0.004).<br /><b>Conclusions</b><br />Latent PVD is a feature of HFpEF and is associated with impaired RV functional reserve, global diastolic filling and LV-CI. This can be quantified by CMR and used to identify patients likely to benefit from IASD implantation.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 23 Jan 2023; epub ahead of print</small></div>
Schuster A, Schulz A, Lange T, Evertz R, ... Hasenfuß G, Backhaus SJ
Eur J Heart Fail: 23 Jan 2023; epub ahead of print | PMID: 36691723
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<div><h4>Staging Heart Failure Patients With Secondary Mitral Regurgitation Undergoing Transcatheter Edge-to-Edge Repair.</h4><i>Stolz L, Doldi PM, Orban M, Karam N, ... Hausleiter J, EuroSMR Investigators</i><br /><b>Background</b><br />Secondary mitral regurgitation (SMR) is a progressive disease with characteristic pathophysiological changes that may influence prognosis. Although the staging of SMR patients suffering from heart failure with reduced ejection fraction (HFrEF) according to extramitral cardiac involvement has prognostic value in medically treated patients, such data are so far lacking for edge-to-edge mitral valve repair (M-TEER).<br /><b>Objectives</b><br />This study sought to classify M-TEER patients into disease stages based on the phenotype of extramitral cardiac involvement and to assess its impact on symptomatic and survival outcomes.<br /><b>Methods</b><br />Based on echocardiographic and clinical assessment, patients were assigned to 1 of the following HFrEF-SMR groups: left ventricular involvement (Stage 1), left atrial involvement (Stage 2), right ventricular volume/pressure overload (Stage 3), or biventricular failure (Stage 4). A Cox regression model was implemented to investigate the impact of HFrEF-SMR stages on 2-year all-cause mortality. The symptomatic outcome was assessed with New York Heart Association functional class at follow-up.<br /><b>Results</b><br />Among a total of 849 eligible patients who underwent M-TEER for relevant SMR from 2008 until 2019, 9.5% (n = 81) presented with left ventricular involvement, 46% (n = 393) with left atrial involvement, 15% (n = 129) with right ventricular pressure/volume overload, and 29% (n = 246) with biventricular failure. An increase in HFrEF-SMR stage was associated with increased 2-year all-cause mortality after M-TEER (HR: 1.39; CI: 1.23-1.58; P < 0.01). Furthermore, higher HFrEF-SMR stages were associated with significantly less symptomatic improvement at follow-up.<br /><b>Conclusions</b><br />The classification of M-TEER patients into HFrEF-SMR stages according to extramitral cardiac involvement provides prognostic value in terms of postinterventional survival and symptomatic improvement.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Cardiovasc Interv: 23 Jan 2023; 16:140-151</small></div>
Stolz L, Doldi PM, Orban M, Karam N, ... Hausleiter J, EuroSMR Investigators
JACC Cardiovasc Interv: 23 Jan 2023; 16:140-151 | PMID: 36697148
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<div><h4>Anxious/Depressive Symptoms Alter the Subjective Perception of Heart Failure Severity in Transthyretin Cardiac Amyloidosis.</h4><i>Ponti L, Smorti M, Pozza F, Argirò A, ... Perfetto F, Cappelli F</i><br /><AbstractText>The subjective perception of cardiac symptom severity is considered a main treatment target in the management of transthyretin-related cardiac amyloidosis (CA), as opposed to objective prognostic markers such as N-terminal pro b-type natriuretic peptide (NT-proBNP), which objectively reflects the severity of heart disease. Nevertheless, anxious and depressive symptoms in patients with CA might affect subjects perceptions of disease, creating a potential gap between objective and subjective parameters. We assess the impact of such bias in consecutive patients with CA. A total of 60 patients aged 62 to 88 years with CA were recruited. The level of anxiety and depression was measured by the Hospital Anxiety and Depression Scale and the subjective perception of symptoms severity by the Kansas City Cardiomyopathy Questionnaire (KCCQ). Finally, NT-proBNP plasma levels at rest and glomerular filtration rate were measured. Nearly 1/2 of the patients (48%) reported clinically relevant levels of psychologic symptoms. Higher levels of anxious and depressive symptoms were significantly linked to lower KCCQ scores. Furthermore, the relation between NT-proBNP and KCCQ was significant only when anxious and depressive symptoms were low (β = -0.86, p = 0.002; β = -0.86, p = 0.002, respectively) and medium (β = -0.49, p = 0.004; β = -0.45, p = 0.004, respectively) but was otherwise lost. Depression and anxiety in patients with transthyretin-related CA required assessment and management. In conclusion, patients with depression/anxiety have a clear disconnect between their personal assessment and objective measures of cardiac symptoms, with a major influence on the patients\' wellbeing and on their subjective response to treatments in clinical trials.</AbstractText><br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 21 Jan 2023; 192:1-6</small></div>
Ponti L, Smorti M, Pozza F, Argirò A, ... Perfetto F, Cappelli F
Am J Cardiol: 21 Jan 2023; 192:1-6 | PMID: 36689900
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<div><h4>miR-448 regulates potassium voltage-gated channel subfamily A member 4 (KCNA4) in ischemia and heart failure.</h4><i>Kang GJ, Xie A, Kim E, Dudley SC</i><br /><b>Background</b><br />MicroRNA ,miR-448, mediates some of the effects of ischemia on arrhythmic risk. Potassium Voltage-gated Channel Subfamily A Member 4 (KCNA4) encodes a K<sub>v</sub>1.4 current that opens in response to membrane depolarization and is essential for regulating action potential duration in heart. KCNA4 has a miR-448 binding site.<br /><b>Objective</b><br />Therefore, we investigated whether miR-448 was involved in the regulation of KCNA4 mRNA expression in ischemia.<br /><b>Methods</b><br />Quantitative real-time reverse-transcriptase polymerase chain reaction was used to investigate the expression of KCNA4 and miR-448. Pull-down assays were used to examine the interaction between miR-448 and KCNA4. A miR-448 decoy and binding site mutation were used to examine specificity of the effect for KCNA4.<br /><b>Results</b><br />The expression of KCNA4 is diminished in ischemia and human HF tissues with ventricular tachycardia. Previously, we have shown miR-448 is upregulated in ischemia, and inhibition can prevent arrhythmic risk after myocardial infarction. The 3\'-UTR of KCNA4 has a conserved miR-448 binding site. MiR-448 bound to this site directly and reduced KCNA4 expression and the transient outward potassium current (Ito). Inhibition of miR-448 restored KCNA4.<br /><b>Conclusion</b><br />These findings showed a link between K<sub>v</sub>1.4 downregulation and miR-448-mediated upregulation in ischemia, suggesting a new mechanism for the antiarrhythmic effect of miR-448 inhibition.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>Heart Rhythm: 21 Jan 2023; epub ahead of print</small></div>
Kang GJ, Xie A, Kim E, Dudley SC
Heart Rhythm: 21 Jan 2023; epub ahead of print | PMID: 36693615
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<div><h4>The Circadian Biology of Heart Failure.</h4><i>El Jamal N, Lordan R, Teegarden SL, Grosser T, FitzGerald G</i><br /><AbstractText>Driven by autonomous molecular clocks that are synchronized by a master pacemaker in the suprachiasmatic nucleus, cardiac physiology fluctuates in diurnal rhythms that can be partly or entirely circadian. Cardiac contractility, metabolism, and electrophysiology, all have diurnal rhythms, as does the neurohumoral control of cardiac and kidney function. In this review, we discuss the evidence that circadian biology regulates cardiac function, how molecular clocks may relate to the pathogenesis of heart failure, and how chronotherapeutics might be applied in heart failure. Disrupting molecular clocks can lead to heart failure in animal models, and the myocardial response to injury seems to be conditioned by the time of day. Human studies are consistent with these findings, and they implicate the clock and circadian rhythms in the pathogenesis of heart failure. Certain circadian rhythms are maintained in patients with heart failure, a factor that can guide optimal timing of therapy. Pharmacologic and nonpharmacologic manipulation of circadian rhythms and molecular clocks show promise in the prevention and treatment of heart failure.</AbstractText><br /><br /><br /><br /><small>Circ Res: 20 Jan 2023; 132:223-237</small></div>
El Jamal N, Lordan R, Teegarden SL, Grosser T, FitzGerald G
Circ Res: 20 Jan 2023; 132:223-237 | PMID: 36656971
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<div><h4>Predictive Modeling to Assess Pretest Probability of Transthyretin Gene Variants Based on Demographic Information.</h4><i>Saef J, Martyn T, Ives L, Roth LR, ... Hanna M, Tang WHW</i><br /><b>Background</b><br />Transthyretin amyloid cardiomyopathy (ATTR-CM) is a morbid condition, though recent advances in diagnosis and therapy stand to change its natural history. Patients\' <i>TTR</i> genotype may guide family screening as more treatments and preventive strategies become available. An efficient, intuitive means of determining pretest genetic risk may better inform patients/clinicians when pursuing genetic testing.<br /><b>Methods</b><br />This is a cohort study of 767 consecutive patients diagnosed with ATTR-CM who underwent genetic testing. Classification and regression trees (CART) analysis created a decision tree assessing likelihood of carrying a pathologic <i>TTR</i> gene variant. Age, sex, and race were used as independent variables. Logistic regression was also performed to model probability of pathologic <i>TTR</i> genotype. The primary outcome was the decision tree\'s accuracy in 2 separate institutions\' ATTR-CM registry.<br /><b>Results</b><br />In our study cohort, 208 patients (27.1%) had ATTRv. Race has served most efficiently as the root node followed by age and sex in a CART algorithm, and showed 88.2% accuracy (75.3% sensitivity, 93.9% specificity) in the validation cohort. The odds of having a <i>TTR</i> gene variant were greater in Black patients compared with non-Black patients (OR, 34.6 [95% CI, 20.5-58.3]; <i>P</i><0.001). Non-Black patients with ATTR-CM aged 69 years and older had <4% risk of having a predisposing mutation.<br /><b>Conclusions</b><br />This CART algorithm incorporating age, sex, and race was able to determine which patients with ATTR-CM have pathogenic <i>TTR</i> mutations with high specificity. Non-Black patients diagnosed at age 69 years or older with ATTR-CM have a low likelihood to have ATTRv.<br /><br /><br /><br /><small>Circ Heart Fail: 20 Jan 2023:e009908; epub ahead of print</small></div>
Saef J, Martyn T, Ives L, Roth LR, ... Hanna M, Tang WHW
Circ Heart Fail: 20 Jan 2023:e009908; epub ahead of print | PMID: 36661045
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<div><h4>Pulmonary transit time of cardiovascular magnetic resonance perfusion scans for quantification of cardiopulmonary haemodynamics.</h4><i>Segeroth M, Winkel DJ, Strebel I, Yang S, ... Bremerich J, Haaf P</i><br /><b>Aims</b><br />Pulmonary transit time (PTT) is the time blood takes to pass from the right ventricle to the left ventricle via pulmonary circulation. We aimed to quantify PTT in routine cardiovascular magnetic resonance imaging perfusion sequences. PTT may help in the diagnostic assessment and characterization of patients with unclear dyspnoea or heart failure (HF).<br /><b>Methods and results</b><br />We evaluated routine stress perfusion cardiovascular magnetic resonance scans in 352 patients, including an assessment of PTT. Eighty-six of these patients also had simultaneous quantification of N-terminal pro-brain natriuretic peptide (NTproBNP). NT-proBNP is an established blood biomarker for quantifying ventricular filling pressure in patients with presumed HF. Manually assessed PTT demonstrated low inter-rater variability with a correlation between raters >0.98. PTT was obtained automatically and correctly in 266 patients using artificial intelligence. The median PTT of 182 patients with both left and right ventricular ejection fraction >50% amounted to 6.8 s (Pulmonary transit time: 5.9-7.9 s). PTT was significantly higher in patients with reduced left ventricular ejection fraction (<40%; P < 0.001) and right ventricular ejection fraction (<40%; P < 0.0001). The area under the receiver operating characteristics curve (AUC) of PTT for exclusion of HF (NT-proBNP <125 ng/L) was 0.73 (P < 0.001) with a specificity of 77% and sensitivity of 70%. The AUC of PTT for the inclusion of HF (NT-proBNP >600 ng/L) was 0.70 (P < 0.001) with a specificity of 78% and sensitivity of 61%.<br /><b>Conclusion</b><br />PTT as an easily, even automatically obtainable and robust non-invasive biomarker of haemodynamics might help in the evaluation of patients with dyspnoea and HF.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J Cardiovasc Imaging: 20 Jan 2023; epub ahead of print</small></div>
Segeroth M, Winkel DJ, Strebel I, Yang S, ... Bremerich J, Haaf P
Eur Heart J Cardiovasc Imaging: 20 Jan 2023; epub ahead of print | PMID: 36662127
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<div><h4>Prognostic value of the severity of clinical congestion in patients hospitalized for decompensated heart failure: Findings from the Japanese KCHF registry.</h4><i>Aida K, Nagao K, Kato T, Yaku H, ... Ozasa N, Kimura T</i><br /><b>Background</b><br />Congestion is a leading cause of hospitalization and a major therapeutic target in patients with heart failure (HF). Clinical practice in Japan is characterized by a long hospital stay, which facilitates more extensive decongestion during hospitalization. We herein examined the time course and prognostic impact of clinical congestion in a large contemporary Japanese cohort of HF.<br /><b>Methods</b><br />Peripheral edema, jugular venous pressure, and orthopnea were graded on a standardized 4-point scale (0 to 3) in 3787 hospitalized patients in a Japanese cohort of HF. Composite congestion scores (CCS) on admission and at discharge were calculated by summing individual scores. The primary outcome was a composite of all-cause death or HF hospitalization.<br /><b>Results</b><br />Median admission CCS was 4 (interquartile range: 3-6). Overall, 255 patients died during the median hospitalization length of 16 days, while 1395 died or were hospitalized for HF during a median post-discharge follow-up of 396 days. The cumulative 1-year incidence of the primary outcome increased at higher tertiles of congestion on admission (32.5, 39.3, and 41.0% in the mild [CCS ≤3], moderate [CCS=4 or 5], and severe [CCS ≥6] congestion groups, respectively, Log-rank P<0.001). The adjusted hazard ratios [HR] (95% confidence interval) of moderate and severe congestion relative to mild congestion were 1.205 (1.065-1.365, P=0.003) and 1.247 (1.103-1.410, P <0.001), respectively. Among 3445 patients discharged alive, 85% had CCS of 0 (complete decongestion) and 15% had CCS ≥1 (residual congestion) at discharge. While residual congestion predicted a risk of post-discharge death or HF hospitalization (adjusted HR: 1.314 [1.145-1.509], P <0.001), admission CCS correlated with the risk of post-discharge death or HF hospitalization, even in the complete decongestion group. No correlation was observed for post-discharge death or HF hospitalization between residual congestion at discharge and admission CCS (P for the interaction=0.316).<br /><b>Conclusion</b><br />In total, 85% of patients were discharged with complete decongestion in Japanese clinical practice. Clinical congestion, on admission and at discharge, was of prognostic value. The severity of congestion on admission was predictive of adverse outcomes, even in the absence of residual congestion.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 20 Jan 2023; epub ahead of print</small></div>
Aida K, Nagao K, Kato T, Yaku H, ... Ozasa N, Kimura T
J Card Fail: 20 Jan 2023; epub ahead of print | PMID: 36690136
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<div><h4>Association of Social Isolation and Loneliness With Incident Heart Failure in a Population-Based Cohort Study.</h4><i>Liang YY, Chen Y, Feng H, Liu X, ... Geng Q, Zhang J</i><br /><b>Background</b><br />Social isolation and loneliness have emerged as important risk factors for cardiovascular diseases, particularly during the coronavirus disease pandemic. However, it is unclear whether social isolation and loneliness had independent and joint associations with incident heart failure (HF).<br /><b>Objectives</b><br />This study sought to examine the association of social isolation, loneliness, and their combination with incident HF.<br /><b>Methods</b><br />The UK Biobank study is a population-based cohort study. Social isolation and loneliness were assessed using self-reported questionnaires. HF cases were identified by linking hospital records and death registries. The weighted polygenic risk score associated with HF was calculated.<br /><b>Results</b><br />Among the 464,773 participants (mean age: 56.5 ± 8.1 years, 45.3% male), 12,898 incident HF cases were documented during a median follow-up of 12.3 years. Social isolation (most vs least: adjusted HR: 1.17; 95% CI:1.11-1.23) and loneliness (yes vs no: adjusted HR: 1.19; 95% CI: 1.11-1.27) were significantly associated with an increased risk of incident HF. The association between an elevated risk of HF and social isolation was modified by loneliness (P<sub>interaction</sub> = 0.034). A gradient of association between social isolation and the risk of incident HF was found only among individuals without loneliness (P<sub>trend</sub> < 0.001), but not among those with loneliness (P<sub>trend</sub> = 0.829). These associations were independent of the genetic risk of HF.<br /><b>Conclusions</b><br />Social isolation and loneliness were independently associated with a higher likelihood of incident HF regardless of genetic risk. The association between social isolation and incident HF was potentially modified by loneliness status.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>JACC Heart Fail: 20 Jan 2023; epub ahead of print</small></div>
Liang YY, Chen Y, Feng H, Liu X, ... Geng Q, Zhang J
JACC Heart Fail: 20 Jan 2023; epub ahead of print | PMID: 36737310
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<div><h4>Disconnect between the effects of serelaxin on renal function and outcome in acute heart failure.</h4><i>Beldhuis IE, Ter Maaten JM, Figarska SM, Damman K, ... Metra M, Voors AA</i><br /><b>Background</b><br />We aimed to study whether improvement in renal function by serelaxin in patients who were hospitalized for acute heart failure (HF) might explain any potential effect on clinical outcomes.<br /><b>Methods</b><br />We included 6318 patients from the RELAXin in AHF-2 (RELAX-AHF2) study. Improvement in renal function was defined as a decrease in serum creatinine of ≥ 0.3 mg/dL and ≥ 25%, or increase in estimated glomerular filtration rate of ≥ 25% between baseline and day 2. Worsening renal function (WRF) was defined as the reverse. We performed causal mediation analyses regarding 180-day all-cause mortality (ACM), cardiovascular death (CVD), and hospitalization for HF/renal failure.<br /><b>Results</b><br />Improvement in renal function was more frequently observed with serelaxin when compared with placebo [OR 1.88 (95% CI 1.64-2.15, p < 0.0001)], but was not associated with subsequent clinical outcomes. WRF occurred less frequent with serelaxin [OR 0.70 (95% CI 0.60-0.83, p < 0.0001)] and was associated with increased risk of ACM, worsening HF and the composite of CVD and HF or renal failure hospitalization. Improvement in renal function did not mediate the treatment effect of serelaxin [CVD HR 1.01 (0.99-1.04), ACM HR 1.01 (0.99-1.03), HF/renal failure hospitalization HR 0.99 (0.97-1.00)].<br /><b>Conclusions</b><br />Despite the significant improvement in renal function by serelaxin in patients with acute HF, the potential beneficial treatment effect was not mediated by improvement in renal function. These data suggest that improvement in renal function might not be a suitable surrogate marker for potential treatment efficacy in future studies with novel relaxin agents in acute HF. Central illustration. Conceptual model explaining mediation analysis; treatment efficacy of heart failure therapies mediated by renal function.<br /><br />© 2023. The Author(s).<br /><br /><small>Clin Res Cardiol: 19 Jan 2023; epub ahead of print</small></div>
Beldhuis IE, Ter Maaten JM, Figarska SM, Damman K, ... Metra M, Voors AA
Clin Res Cardiol: 19 Jan 2023; epub ahead of print | PMID: 36656377
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<div><h4>Pulmonary Hypertension Phenotype Can Be Identified in Heart Failure with Reduced Ejection Fraction Using Echocardiographic Assessment of Pulmonary Artery Pressure with Supportive Use of Pressure Reflection Variables.</h4><i>Bech-Hanssen O, Smith JG, Astengo M, Bollano E, ... Bergh N, Karason K</i><br /><b>Background</b><br />Pulmonary hypertension (PH) is frequent in patients with heart failure and reduced ejection fraction (HFrEF) with two different phenotypes: isolated post-capillary PH (IpcPH) and, with worst prognosis, combined pre- and post-capillary PH (CpcPH). The aims of the present echocardiography study were to investigate (1) the ability to identify PH-phenotype in patients with HFrEF using the newly adopted definition of PH (mean pulmonary artery pressure >20 mmHg), and (2) the relationship between PH-phenotype and right ventricular (RV) function.<br /><b>Methods</b><br />One hundred and twenty-four patients with HFrEF consecutively referred for heart transplant or heart failure work-up were included with echocardiography and right heart catheterization within 48 hours. We estimated systolic pulmonary artery pressure (sPAP<sub>Doppler</sub>) and used a method to detect increased pulmonary vascular resistance (PVR>3 Wood units) based on predefined thresholds of three pressure reflection (PRefl) variables (the acceleration time in the RV outflow tract (RVOT), the interval between peak RVOT- and peak tricuspid regurgitant velocity and the RV pressure augmentation following peak RVOT velocity).<br /><b>Results</b><br />Using ROC analysis in a derivation group (n=62) we identified sPAP<sub>Doppler</sub> ≥35 mmHg as a cutoff that in a test group (n=62) increased the likelihood of PH 6.6-fold. The presence of sPAP<sub>Doppler</sub> >40 mmHg and two or three positive PRefl variables increased the probability of CpcPH 6 to 8-fold. A two-step approach with primarily assessment of sPAP<sub>Doppler</sub> and the supportive use of PRefl variables in patients with mild/moderate PH (sPAP<sub>Doppler</sub> 41-59 mmHg), showed 76% observer agreement and a weighted kappa of 0.63. The steady state (PVR) and pulsatile (compliance, elastance) vascular loading are increased in both IpcPH and CpcPH with comparable degree of RV dysfunction.<br /><b>Conclusions</b><br />The PH phenotype can be identified in HFrEF using standard echocardiographic assessment of PA pressure with supportive use of PRefl variables in patients with mild to moderate PH.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Am Soc Echocardiogr: 18 Jan 2023; epub ahead of print</small></div>
Bech-Hanssen O, Smith JG, Astengo M, Bollano E, ... Bergh N, Karason K
J Am Soc Echocardiogr: 18 Jan 2023; epub ahead of print | PMID: 36681129
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<div><h4>Effect of allogeneic adipose tissue derived mesenchymal stromal cell treatment in chronic ischemic heart failure with reduced ejection fraction - The SCIENCE Trial.</h4><i>Qayyum AA, van Klarenbosch B, Frljak S, Cerar A, ... Kastrup J, SCIENCE Investigators</i><br /><b>Background:</b><br/>and aims</b><br />The aim of the SCIENCE trial was to investigate whether a single treatment with direct intramyocardial injections of adipose tissue derived mesenchymal stromal cells (CSCC_ASCs) was safe and improved cardiac function in patients with chronic ischemic heart failure with reduced ejection fraction (HFrEF).<br /><b>Methods</b><br />The study was a European multi-centre double-blinded placebo-controlled phase II trial using allogeneic CSCC_ASCs from healthy donors or placebo (2:1 randomization). Main inclusion criteria were NYHA II-III, left ventricular ejection fraction (LVEF) < 45%, and NT-ProBNP levels>300 pg/mL. CSCC_ASCs or placebo (isotonic saline) were injected directly into viable myocardium. Primary endpoint was change in left ventricular end-systolic volume (LVESV) at 6 months follow up measured by echocardiography.<br /><b>Results</b><br />A total of 133 symptomatic HFrEF patients were included. The treatment was safe without any drug-related severe adverse events or difference in cardiac related adverse events during a 3-years follow-up period. There were no significant differences between the groups during follow up in LVESV (0.3 ± 5.0 ml, P = 0.945), nor in secondary endpoints left ventricular end-diastolic volume (-2.0 ± 6.0 ml, P = 0.736) and LVEF (-1.6 ± 1.0%, P = 0.119). The NYHA classification improved slightly within the first year in both groups without any difference between groups. There were no changes in 6-Minute Walk Test, NT-ProBNP, CRP or quality-of-life the first year in any of the two groups.<br /><b>Conclusion</b><br />The SCIENCE trial demonstrated safety of intramyocardial allogeneic CSCC_ASC therapy in patients with chronic HFrEF. However, it was not possible to improve the predefined endpoints and induce restoration of cardiac function or clinical symptoms.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 16 Jan 2023; epub ahead of print</small></div>
Qayyum AA, van Klarenbosch B, Frljak S, Cerar A, ... Kastrup J, SCIENCE Investigators
Eur J Heart Fail: 16 Jan 2023; epub ahead of print | PMID: 36644821
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<div><h4>Prevalence, Characteristics and Outcomes of Older Patients with Hereditary versus Wild-Type Transthyretin Amyloid Cardiomyopathy.</h4><i>Porcari A, Razvi Y, Masi A, Patel R, ... Fontana M, Gillmore JD</i><br /><b>Background</b><br />Transthyretin amyloid cardiomyopathy (ATTR-CM) is often assumed to be associated with wild-type TTR genotype (ATTRwt) in elderly patients (aged >70), some of whom are not offered genetic testing. We sought to estimate the prevalence, clinical characteristics and prognostic implications of TTR variants among elderly patients diagnosed with ATTR-CM.<br /><b>Methods</b><br />Data from consecutive patients over 70 years of age diagnosed with ATTR-CM at the UK National Amyloidosis Centre between January 2010 and August 2022 were retrospectively evaluated. All patients underwent clinical evaluation, biochemical tests, echocardiography and TTR genotyping. The study outcome was all-cause mortality.<br /><b>Results</b><br />The study population consisted of 2029 patients with ATTR-CM (median age 79 years at diagnosis, 13.2% females, 80.4% Caucasian). Variant ATTR-CM (ATTRv-CM) was diagnosed in 20.7% (n=421) of the study population of whom 329 (76.3%) carried V122I, 49 (11.4%) T60A, 18 (4.2%) V30M and 35 (8.1%) other pathogenic TTR variants. During a median (range) follow up of 29 (12-48) months, ATTRv-CM was associated with increased all-cause mortality compared to ATTRwt-CM, with the poorest survival observed in V122I-associated ATTRv-CM (p<0.001). Univariable and multivariable logistic regression analyses in those with ATTR-CM showed younger age at diagnosis (odds ratio [OR] 0.85 per year, p<0.001), female sex (OR 2.73, p<0.001), Afro-Caribbean ethnicity (OR 65.5, p<0.001), atrial fibrillation (OR 0.65, p=0.015), ischemic heart disease (OR 0.54, p=0.007), peripheral polyneuropathy (OR 5.70, p<0.001) and orthostatic hypotension (OR 6.29, p<0.001) to be independently associated with ATTRv-CM.<br /><b>Conclusion</b><br />Up to 20.7% of elderly patients with ATTR-CM have a pathogenic TTR variant. These findings support routine sequencing of the TTR gene in all patients with ATTR-CM regardless of age. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 16 Jan 2023; epub ahead of print</small></div>
Porcari A, Razvi Y, Masi A, Patel R, ... Fontana M, Gillmore JD
Eur J Heart Fail: 16 Jan 2023; epub ahead of print | PMID: 36644836
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<div><h4>Cost-effectiveness of immediate initiation of dapagliflozin in patients with a history of heart failure.</h4><i>Miller RJ, Chew DS, Qin L, Fine NM, ... Howlett JG, McEwan P</i><br /><b>Aims</b><br />To compare the cost-effectiveness of immediate and 12 months delayed initiation of dapagliflozin treatment in patients with a history of hospitalization for heart failure (HHF) from the UK, Canadian, German, and Spanish healthcare perspectives.<br /><b>Methods and results</b><br />A cost-utility analysis was conducted using a decision-analytic Markov model with health states defined by Kansas City Cardiomyopathy Questionnaire (KCCQ) scores (shown in the graphical abstract), type 2 diabetes mellitus status (T2DM) and incidence of heart failure (HF) events. Patient-level data for patients with prior HHF from the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial was used to inform the model inputs on clinical events and utility values. Healthcare costs were sourced from the relevant national reference databases and the published literature. Compared to standard therapy, immediate initiation of dapagliflozin decreased HHF (187 events), urgent HF visits (32 events) and cardiovascular mortality (18 events). Standard therapy was associated with lifetime costs of £13,224 and 4.02 QALYs. Twelve months delayed initiation of dapagliflozin was associated with total discounted lifetime costs and QALYs of £16,660 and 4.61 respectively compared to £16,912 and 4.66 respectively for immediate initiation. Compared to standard therapy, immediate and 12 months delayed initiation of dapagliflozin yielded incremental cost-effectiveness ratio (ICER) £5,779 and £5,821, respectively. Compared to 12 months delayed initiation, immediate initiation of dapagliflozin had an ICER of £5,263. Results were similar from the Canadian, German, and Spanish healthcare perspectives.<br /><b>Conclusion</b><br />Both immediate and 12 months delayed initiation of dapagliflozin are cost-effective. However, immediate initiation provides greater clinical benefits, with almost 10% additional QALYs gain, compared 12 months delayed initiation of dapagliflozin and should be considered standard of care. This article is protected by copyright. All rights reserved.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 16 Jan 2023; epub ahead of print</small></div>
Miller RJ, Chew DS, Qin L, Fine NM, ... Howlett JG, McEwan P
Eur J Heart Fail: 16 Jan 2023; epub ahead of print | PMID: 36644849
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<div><h4>Use of Patient-Reported Outcomes in Heart Failure: From Clinical Trials to Routine Practice.</h4><i>Savarese G, Lindenfeld J, Stolfo D, Adams K, ... Rosano GMC, Allen LA</i><br /><AbstractText>Heart failure (HF) is a complex syndrome that affects mortality/morbidity and acts at different levels in the patient\'s life, resulting in a drastic impairment in multiple aspects of daily activities (eg,: physical, mental/emotional, and social) and leading to a reduction in quality of life. The definition of disease status and symptom severity has been traditionally based on the physician assessment, while the patient\'s experience of disease has been long overlooked. The active participation of patients in their own care is necessary to better understand the perception of disease and the multiple aspects of life affected, and to improve adherence to treatments. Patient-reported outcomes (PROs) aim to switch traditional care to a more patient-centered approach. Although PROs demonstrated precision in the evaluation of disease status and have a good association with prognosis in several randomized controlled trials, their implementation into clinical practice is limited. This review discusses the modalities of use of PROs in HF, summarizes the most largely adopted PROs in HF care, and provides an overview on the application of PROs in trials and the potential for their transition to clinical practice. By discussing the advantages and the disadvantages of their use, the reasons limiting their application in daily clinical routine, and the strategies that may promote their implementation, this review aims to foster the systematic integration of the patient\'s standpoint in HF care. This article is protected by copyright. All rights reserved.</AbstractText><br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 16 Jan 2023; epub ahead of print</small></div>
Savarese G, Lindenfeld J, Stolfo D, Adams K, ... Rosano GMC, Allen LA
Eur J Heart Fail: 16 Jan 2023; epub ahead of print | PMID: 36644876
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<div><h4>Acute heart failure after non-cardiac surgery: incidence, phenotypes, determinants and outcomes.</h4><i>Gualandro DM, Puelacher C, Chew MS, Andersson H, ... Mueller C, BASEL-PMI Investigators</i><br /><b>Aims</b><br />Primary acute heart failure (AHF) is a common cause of hospitalization. AHF may also develop postoperatively (pAHF). The aim of this study was to assess the incidence, phenotypes, determinants and outcomes of pAHF following non-cardiac surgery.<br /><b>Methods and results</b><br />9,164 consecutive high-risk patients undergoing 11,262 non-cardiac inpatient surgeries were prospectively included. The incidence, phenotypes, determinants and outcome of pAHF, centrally adjudicated by independent cardiologists, was determined. The incidence of pAHF was 2.5% (95% confidence interval [CI] 2.2-2.8%). 51% of pAHF occurred in patients without known HF (de novo pAHF), and 49% in patients with chronic HF. Among patients with chronic HF, 10% developed pAHF, and among patients without a history of HF, 1.5% developed pAHF. Chronic HF, diabetes, urgent/emergent surgery, atrial fibrillation, cardiac troponin elevations above the 99<sup>Th</sup> percentile, chronic obstructive pulmonary disease, anemia, peripheral artery disease, coronary artery disease, and age , , , were independent predictors of pAHF in the logistic regression model. Patients with pAHF had significantly higher all-cause mortality (44% vs. 11%, p<.001) and AHF readmission (15% vs. 2%, p< .001) within one year than patients without pAHF. After cox regression analysis, pAHF was an independent predictor of all-cause mortality (adjusted hazard ratio [aHR] 1.7 [95%CI 1.3-2.2]; P<.001) and AHF readmission (aHR 2.3 [95%CI 1.5-3.7]; P<.001). Findings were confirmed in an external validation cohort using a prospective multicenter cohort of 1250 patients (incidence of pAHF 2.4% [95%CI, 1.6-3.3%]).<br /><b>Conclusions</b><br />pAHF frequently developed following non-cardiac surgery, being de novo in half of cases, and associated with a very high mortality.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 16 Jan 2023; epub ahead of print</small></div>
Gualandro DM, Puelacher C, Chew MS, Andersson H, ... Mueller C, BASEL-PMI Investigators
Eur J Heart Fail: 16 Jan 2023; epub ahead of print | PMID: 36644890
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<div><h4>Association of central obesity with unique cardiac remodelling in young adults born small for gestational age.</h4><i>Bernardino G, Sepúlveda-Martínez Á, Rodríguez-López M, Prat-González S, ... Bijnens B, Crispi F</i><br /><b>Aims</b><br />Being born small for gestational age (SGA, 10% of all births) is associated with increased risk of cardiovascular mortality in adulthood together with lower exercise tolerance, but mechanistic pathways are unclear. Central obesity is known to worsen cardiovascular outcomes, but it is uncertain how it affects the heart in adults born SGA. We aimed to assess whether central obesity makes young adults born SGA more susceptible to cardiac remodelling and dysfunction.<br /><b>Methods and results</b><br />A perinatal cohort from a tertiary university hospital in Spain of young adults (30-40 years) randomly selected, 80 born SGA (birth weight below 10th centile) and 75 with normal birth weight (controls) was recruited. We studied the associations between SGA and central obesity (measured via the hip-to-waist ratio and used as a continuous variable) and cardiac regional structure and function, assessed by cardiac magnetic resonance using statistical shape analysis. Both SGA and waist-to-hip were highly associated to cardiac shape (F = 3.94, P < 0.001; F = 5.18, P < 0.001 respectively) with a statistically significant interaction (F = 2.29, P = 0.02). While controls tend to increase left ventricular end-diastolic volumes, mass and stroke volume with increasing waist-to-hip ratio, young adults born SGA showed a unique response with inability to increase cardiac dimensions or mass resulting in reduced stroke volume and exercise capacity.<br /><b>Conclusion</b><br />SGA young adults show a unique cardiac adaptation to central obesity. These results support considering SGA as a risk factor that may benefit from preventive strategies to reduce cardiometabolic risk.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.<br /><br /><small>Eur Heart J Cardiovasc Imaging: 16 Jan 2023; epub ahead of print</small></div>
Bernardino G, Sepúlveda-Martínez Á, Rodríguez-López M, Prat-González S, ... Bijnens B, Crispi F
Eur Heart J Cardiovasc Imaging: 16 Jan 2023; epub ahead of print | PMID: 36644919
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<div><h4>Reverse Atrial Remodeling in Heart Failure With Recovered Ejection Fraction.</h4><i>Sun Y, Chen X, Zhang Y, Yu Y, ... Tse G, Liu Y</i><br /><AbstractText><br /><b>Background:</b><br/>Heart failure with recovered ejection fraction (HFrecEF) has been a newly recognized entity since 2020. However, the concept has primarily focused on left ventricular ejection fraction improvement, with less focus on the recovery of the left atrium. In this study, we investigated changes in left atrial (LA) echocardiographic indices in HFrecEF. Methods and Results An inpatient cohort with heart failure with reduced ejection fraction (HFrEF) was identified retrospectively and followed up prospectively in a single tertiary hospital. The enrolled patients were classified into HFrecEF and persistent HFrEF groups. Alternations in LA parameters by echocardiography were calculated. The primary outcome was a composite of cardiovascular death or heart failure rehospitalization. A total of 699 patients were included (HFrecEF: n=228; persistent HFrEF: n=471). Compared with persistent HFrEF, the HFrecEF group had greater reductions in LA diameter, LA transverse diameter, LA superior-inferior diameter, LA volume, and LA volume index but not in LA sphericity index. Cox regression analysis showed that the HFrecEF group experienced lower risks of prespecified end points than the persistent HFrEF group after adjusting for confounders. Additionally, 136 (59.6%) and 62 (13.0%) patients showed LA reverse remodeling (LARR) for the HFrecEF and persistent HFrEF groups, respectively. Among the HFrecEF subgroup, patients with LARR had better prognosis compared with those without LARR. Multivariate logistic analysis demonstrated that age and coronary heart disease were 2 independent negative predictors for LARR. <br /><b>Conclusions:</b><br/>In HFrecEF, both left ventricular systolic function and LA structure remodeling were improved. Patients with HFrecEF with LARR had improved clinical outcomes, indicating that the evaluation of LA size provides a useful biomarker for risk stratification of heart failure.</AbstractText><br /><br /><br /><br /><small>J Am Heart Assoc: 16 Jan 2023:e8124; epub ahead of print</small></div>
Sun Y, Chen X, Zhang Y, Yu Y, ... Tse G, Liu Y
J Am Heart Assoc: 16 Jan 2023:e8124; epub ahead of print | PMID: 36645090
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<div><h4>Transcatheter valve-in-valve or valve-in-ring implantation with a novel balloon-expandable device in patients with bioprosthetic left side heart valves failure: 1-year follow-up from a multicenter experience.</h4><i>Moscarella E, Ielasi A, Mussayev A, Montorfano M, ... Bedogni F, Tespili M</i><br /><b>Background</b><br />Transcatheter aortic and mitral valve-in-valve (ViV) or valve-in-ring (ViR) implantation into failed bioprosthetic heart valves (BHVs) or rings represents an appealing, less invasive, treatment option for patients at high surgical risk. Nowadays, few data have been reported on the use of balloon-expandable Myval (Meril Life Science, Vapi, India) transcatheter heart valve (THV) for the treatment of degenerated BHVs or rings. We aimed at evaluating the early and mid-term clinical outcomes of patients with left side heart bioprosthesis deterioration treated with transcatheter ViV/ViR implantation using Myval THV.<br /><b>Methods</b><br />97 consecutive patients with symptomatic, severe aortic(n=33) and mitral(n=64) BHVs/ring dysfunction underwent transcatheter aortic ViV and mitral ViV/ViR implantation with Myval THV.<br /><b>Results</b><br />Technical success was achieved in 95 (98%) of the patients. Two cases of acute structural trans-catheter mitral ViV/ViR dysfunction requiring a second THV implantation were reported. At 30-day, a significant reduction in prosthetic trans-valvular pressure gradients and increase in valve areas were seen following both aortic and mitral ViV/ViR implantation. Overall survival at 15 months (IQR 8-21) was 92%. Patients undergoing mitral ViV/ViR had a relatively worse survival compared with those undergoing aortic ViV implantation (89% vs. 97% respectively; HR:2.7,CI:0.33-22.7;p=0.34). At longest follow-up available a significant improvement in NYHA functional class I and II was observed in patients with aortic and mitral ViV/ViR implantation(93.8% and 92.1%).<br /><b>Conclusions</b><br />Despite high surgical risk, transcatheter ViV/ViR implantation for failed left side heart bioprosthesis can be performed safely using Myval THV with a high success rate and low early and mid-term mortality and morbidity.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 16 Jan 2023; epub ahead of print</small></div>
Moscarella E, Ielasi A, Mussayev A, Montorfano M, ... Bedogni F, Tespili M
Int J Cardiol: 16 Jan 2023; epub ahead of print | PMID: 36657566
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<div><h4>Investigator-reported ventricular arrhythmias and mortality in heart failure with mildly reduced or preserved ejection fraction.</h4><i>Curtain JP, Adamson C, Kondo T, Butt J, ... Jhund PS, McMurray JJV</i><br /><b>Aims</b><br />Few reports have examined the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) or their relationship with mortality in patients with heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF).<br /><b>Methods and results</b><br />Data from the PARAGON-HF, TOPCAT, I-Preserve, and CHARM-Preserved trials were merged. VT/VF, reported as adverse events, were identified. Patients who experienced VT/VF were compared with patients who did not. The relationship between VT/VF and mortality was examined in time-updated Cox proportional hazard regression models. Variables associated with VT/VF were examined in Cox proportional hazard regression models. The rate of VT/VF in patients with HFmrEF compared with patients with HFpEF was examined in a Cox proportional hazards regression model. Of 13 609 patients, over a median follow-up of 1170 days (interquartile range: 966-1451), 146 (1.1%) experienced an investigator-reported VT/VF (incidence rate 0.3 per 100 person-years). Patients who experienced VT/VF were more likely to be male, have had a myocardial infarction, poorer renal function, more adverse left ventricular remodelling, and higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) than patients who did not. Occurrence of VT/VF was associated with NT-proBNP, history of atrial fibrillation/flutter, male sex, lower ejection fraction, and history of hypertension. VT/VF was associated with all-cause death [adjusted hazard ratio (HR): 3.95, 95% confidence interval (CI): 2.80-5.57; P < 0.001] and cardiovascular death, driven by death from heart failure and not sudden death. Patients with HFmrEF had a higher rate of VT/VF than patients with HFpEF (adjusted HR: 2.19, 95% CI: 1.77-2.71).<br /><b>Conclusion</b><br />VT/VF was uncommon in patients with HFmrEF and HFpEF. However, such events were strongly associated with mortality and appear to be a marker of disease severity rather than risk of sudden death.<br /><b>Clinical trial registration</b><br />ClinicalTrials.gov unique identifier: NCT01920711(PARAGON-HF); NCT00094302 (TOPCAT); NCT00095238 (I-Preserve); NCT00634712 (CHARM-Preserved).<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 12 Jan 2023; epub ahead of print</small></div>
Curtain JP, Adamson C, Kondo T, Butt J, ... Jhund PS, McMurray JJV
Eur Heart J: 12 Jan 2023; epub ahead of print | PMID: 36632831
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<div><h4>Incidence, Predictors, and Outcomes of Major Bleeding Among Patients Hospitalized With Acute Heart Failure.</h4><i>Abramov D, Kobo O, Gorodeski EZ, Rana JS, ... Sauer AJ, Mamas MA</i><br /><AbstractText>Acute heart failure (AHF) is a common etiology of hospitalization and is associated with morbidity, including bleeding. In this study, the authors sought to assess the incidence, types, and associates of major bleeding in patients hospitalized with AHF. The National Inpatient Sample from October 2015 to December 2018 was used to identify patients with AHF. The incidence of common bleeding etiologies, and patient demographics, co-morbidities, associated acute cardiac diagnoses, and invasive procedures, were identified. The multivariable logistic regression was used to identify predictors of bleeding and the association of bleeding episodes with inpatient mortality. During the study period, 1,106,634 patients were admitted with a primary diagnosis of AHF, of whom 58,955 (5.3%) had an episode of bleeding. Common bleeding sources were gastrointestinal (25.7%), hematuria (24%), respiratory (23.6%), and procedure-related bleeding (2.5%). Major bleeding was more common in patients with AHF with preserved ejection fraction (odds ratio 1.14, confidence interval 1.12 to 1.16, p <0.001) versus AHF with reduced ejection fraction and in men (odds ratio 1.3, confidence interval 1.29 to 1.31, p <0.001). Major bleeding was associated with higher mortality (7.0% vs 2.4%, p <0.001), longer length of stay (7 vs 4 days, p <0.001), and higher inpatient costs ($49,658 vs $27,636, p <0.001). In conclusion, major bleeding occurs in 5.3% of patients hospitalized with AHF and is associated with higher inpatient mortality and costs and longer length of stay.</AbstractText><br /><br />Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 12 Jan 2023; 191:59-65</small></div>
Abramov D, Kobo O, Gorodeski EZ, Rana JS, ... Sauer AJ, Mamas MA
Am J Cardiol: 12 Jan 2023; 191:59-65 | PMID: 36640601
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<div><h4>Outcomes in patients with cardiac amyloidosis undergoing heart transplantation: the eurotransplant experience.</h4><i>Kraus MJ, Smits JM, Meyer AL, Strelniece A, ... Frey N, Kreusser MM</i><br /><b>Background</b><br />When advanced heart failure occurs in cardiac amyloidosis, prognosis is poor. In this setting heart transplantation (HTX) is a treatment option for selected patients. We here present the results of post-transplantation outcomes in cardiac amyloidosis within the Eurotransplant area, investigating possible predictors of survival.<br /><b>Methods</b><br />Of 115 patients undergoing HTX due to cardiac amyloidosis in the Eurotransplant region between November 1987 and May 2020, detailed assessment prior to transplantation was available in 85 patients. The present study was conducted in a retrospective approach. Primary endpoint was mortality after HTX. Baseline variables were entered in a Cox proportional hazards model with the primary endpoint as a dependent variable.<br /><b>Results</b><br />Median overall survival following HTX was 6.3 years in the overall collective and the subgroup. Univariate Cox proportional hazards model revealed a significant relationship between overall survival and the transplantation period (2008 to 2020 vs 1987 to 2007; median survival 9.7 years vs 1.8 years, hazard ratio 0.45, p = 0.01). Further predictors were albumin concentration (hazard ratio 0.92, p < 0.001), and systolic blood pressure (hazard ratio 0.96, p < 0.001). The transplant period as well as albumin concentration remained significant independent predictors in the AL sub cohort in a multivariate Cox proportional hazards model.<br /><b>Conclusions</b><br />HTX is a viable treatment option for patients at an advanced stage of cardiac amyloidosis as overall survival after transplantation has improved in the modern age. Patients at a very advanced stage of the disease, indicated by low serum albumin and blood pressure, show worse outcomes following HTX. Optimal timing and careful patient selection may therefore be particularly important to further improve post-HTX survival in amyloidosis patients.<br /><br />Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Heart Lung Transplant: 12 Jan 2023; epub ahead of print</small></div>
Kraus MJ, Smits JM, Meyer AL, Strelniece A, ... Frey N, Kreusser MM
J Heart Lung Transplant: 12 Jan 2023; epub ahead of print | PMID: 36710093
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<div><h4>The End of Endomyocardial Biopsy?: A Practical Guide for Noninvasive Heart Transplant Rejection Surveillance.</h4><i>Holzhauser L, DeFilippis EM, Nikolova A, Byku M, ... Khush KK, Vest AR</i><br /><AbstractText>Noninvasive heart transplant rejection surveillance using gene expression profiling (GEP) to monitor immune activation is widely used among heart transplant programs. With the new development of donor-derived cell-free DNA (dd-cfDNA) assays, more programs are transitioning to a predominantly noninvasive rejection surveillance protocol with a reduced frequency of endomyocardial biopsies. As a result, many practical questions arise that potentially delay implementation of these valuable new tools. The purpose of this review is to provide practical guidance for clinicians transitioning toward a less invasive acute rejection monitoring protocol after heart transplantation, and to answer 10 common questions about the GEP and dd-cfDNA assays. Evidence supporting GEP and dd-cfDNA testing is reviewed, as well as guidance on test interpretation and future directions.</AbstractText><br /><br />Copyright © 2022. Published by Elsevier Inc.<br /><br /><small>JACC Heart Fail: 11 Jan 2023; epub ahead of print</small></div>
Holzhauser L, DeFilippis EM, Nikolova A, Byku M, ... Khush KK, Vest AR
JACC Heart Fail: 11 Jan 2023; epub ahead of print | PMID: 36682960
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<div><h4>Patient Eligibility for Established and Novel Guideline-Directed Medical Therapies After Acute Heart Failure Hospitalization.</h4><i>Moghaddam N, Hawkins NM, McKelvie R, Poon S, ... Zieroth S, Virani SA</i><br /><b>Background</b><br />Acute heart failure (AHF) hospitalization presents an opportunity to optimize pharmacotherapy to improve outcomes.<br /><b>Objectives</b><br />This study\'s aim was to define eligibility for initiation of guideline-directed medical therapy and newer heart failure (HF) agents from recent clinical trials in the AHF population.<br /><b>Methods</b><br />The authors analyzed patients with an AHF admission within the CAN-HF (Canadian Heart Failure) registry between January 2017 and April 2020. Heart failure with reduced ejection fraction (HFrEF) was defined as left ventricular ejection fraction (LVEF) ≤40% and heart failure with preserved ejection fraction (HFpEF) as LVEF >40%. Eligibility was assessed according to the major society guidelines or enrollment criteria from recent landmark clinical trials.<br /><b>Results</b><br />A total of 809 patients with documented LVEF were discharged alive from hospital: 455 with HFrEF and 354 with HFpEF; of these patients, 284 had a de novo presentation and 525 had chronic HF. In HFrEF patients, eligibility for therapies was 73.6% for angiotensin receptor-neprilysin inhibitors (ARNIs), 94.9% for beta-blockers, 84.4% for mineralocorticoid receptor antagonists (MRAs), 81.1% for sodium/glucose cotransporter 2 (SGLT2) inhibitors, and 15.6% for ivabradine. Additionally, 25.9% and 30.1% met trial criteria for vericiguat and omecamtiv mecarbil, respectively. Overall, 71.6% of patients with HFrEF (75.5% de novo, 69.5% chronic HF) were eligible for foundational quadruple therapy. In the HFpEF population, 37.6% and 59.9% were eligible for ARNIs and SGLT2 inhibitors based on recent trial criteria, respectively.<br /><b>Conclusions</b><br />The majority of patients admitted with AHF are eligible for foundational quadruple therapy and additional novel medications across a spectrum of HF phenotypes.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>JACC Heart Fail: 11 Jan 2023; epub ahead of print</small></div>
Moghaddam N, Hawkins NM, McKelvie R, Poon S, ... Zieroth S, Virani SA
JACC Heart Fail: 11 Jan 2023; epub ahead of print | PMID: 36732099
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<div><h4>Non-invasive diagnosis of transthyretin cardiac amyloidosis utilizing typical late gadolinium enhancement pattern on cardiac magnetic resonance and light chains.</h4><i>Slivnick JA, Alvi N, Singulane CC, Scheetz S, ... Zareba KM, Patel AR</i><br /><b>Aims</b><br />While cardiac magnetic resonance (CMR) is often obtained early in the evaluation of suspected cardiac amyloidosis (CA), it currently cannot be utilized to differentiate immunoglobulin (AL) and transthyretin (ATTR) CA. We aimed to determine whether a novel CMR and light-chain biomarker-based algorithm could accurately diagnose ATTR-CA.<br /><b>Methods and results</b><br />Patients with confirmed AL or ATTR-CA with typical late gadolinium enhancement (LGE) and Look-Locker pattern for CA on CMR were retrospectively identified at three academic medical centres. Comprehensive light-chain analysis including free light chains, serum, and urine electrophoresis/immunofixation was performed. The diagnostic accuracy of the typical CMR pattern for CA in combination with negative light chains for the diagnosis of ATTR-CA was determined both in the entire cohort and in the subset of patients with invasive tissue biopsy as the gold standard. A total of 147 patients (age 70 ± 11, 76% male, 51% black) were identified: 89 ATTR-CA and 58 AL-CA. Light-chain biomarkers were abnormal in 81 (55%) patients. Within the entire cohort, the sensitivity and specificity of a typical LGE and Look-Locker CMR pattern and negative light chains for ATTR-CA was 73 and 98%, respectively. Within the subset with biopsy-confirmed subtype, the CMR and light-chain algorithm were 69% sensitive and 98% specific.<br /><b>Conclusion</b><br />The combination of a typical LGE and Look-Locker pattern on CMR with negative light chains is highly specific for ATTR-CA. The successful non-invasive diagnosis of ATTR-CA using CMR has the potential to reduce diagnostic and therapeutic delays and healthcare costs for many patients.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.<br /><br /><small>Eur Heart J Cardiovasc Imaging: 10 Jan 2023; epub ahead of print</small></div>
Slivnick JA, Alvi N, Singulane CC, Scheetz S, ... Zareba KM, Patel AR
Eur Heart J Cardiovasc Imaging: 10 Jan 2023; epub ahead of print | PMID: 36624559
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<div><h4>Cardiac magnetic resonance in giant cell myocarditis: a matched comparison with cardiac sarcoidosis.</h4><i>Pöyhönen P, Nordenswan HK, Lehtonen J, Syväranta S, Shenoy C, Kupari M</i><br /><b>Aims</b><br />Giant cell myocarditis (GCM) is an inflammatory cardiomyopathy akin to cardiac sarcoidosis (CS). We decided to study the findings of GCM on cardiac magnetic resonance (CMR) imaging and to compare GCM with CS.<br /><b>Methods and results</b><br />CMR studies of 18 GCM patients were analyzed and compared with 18 CS controls matched for age, sex, left ventricular (LV) ejection fraction and presenting cardiac manifestations. The analysts were blinded to clinical data. On admission, the duration of symptoms (median) was 0.2 months in GCM vs. 2.4 months in CS (P = 0.002), cardiac troponin T was elevated (>50 ng/L) in 16/17 patients with GCM and in 2/16 with CS (P < 0.001), their respective median plasma B-type natriuretic propeptides measuring 4488 ng/L and 1223 ng/L (P = 0.011). On CMR imaging, LV diastolic volume was smaller in GCM (177 ± 32 mL vs. 211 ± 58 mL, P = 0.014) without other volumetric or wall thickness measurements differing between the groups. Every GCM patient had multifocal late gadolinium enhancement (LGE) in a distribution indistinguishable from CS both longitudinally, circumferentially, and radially across the LV segments. LGE mass averaged 17.4 ± 6.3% of LV mass in GCM vs 25.0 ± 13.4% in CS (P = 0.037). Involvement of insertion points extending across the septum into the right ventricular wall, the \"hook sign\" of CS, was present in 53% of GCM and 50% of CS.<br /><b>Conclusion</b><br />In GCM, CMR findings are qualitatively indistinguishable from CS despite myocardial inflammation being clinically more acute and injurious. When matched for LV dysfunction and presenting features, LV size and LGE mass are smaller in GCM.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J Cardiovasc Imaging: 10 Jan 2023; epub ahead of print</small></div>
Pöyhönen P, Nordenswan HK, Lehtonen J, Syväranta S, Shenoy C, Kupari M
Eur Heart J Cardiovasc Imaging: 10 Jan 2023; epub ahead of print | PMID: 36624560
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<div><h4>Dietary essential amino acids for the treatment of heart failure with reduced ejection fraction.</h4><i>Ragni M, Greco CM, Felicetta A, Ren SV, ... Condorelli G, Nisoli E</i><br /><b>Aims</b><br />Heart failure with reduced ejection fraction (HFrEF) is a leading cause of mortality worldwide, requiring novel therapeutic and lifestyle interventions. Metabolic alterations and energy production deficit are hallmarks and thereby promising therapeutic targets for this complex clinical syndrome. We aim to study the molecular mechanisms and effects on cardiac function in rodents with HFrEF of a designer diet in which free essential amino acids - in specifically designed percentages - substituted for protein.<br /><b>Methods and results</b><br />Wild-type mice were subjected to transverse aortic constriction (TAC) to induce left ventricle (LV) pressure overload or sham surgery. Whole body glucose homeostasis was studied with glucose tolerance test, while myocardial dysfunction and fibrosis were measured with echocardiogram and histological analysis. Mitochondrial bioenergetics and morphology were investigated with oxygen consumption rate measurement and electron microscopy evaluation. Circulating and cardiac non-targeted metabolite profiles were analyzed by ultrahigh performance liquid chromatography-tandem mass spectroscopy, while RNA sequencing was used to identify signalling pathways mainly affected. The amino acid-substituted diet shows remarkable preventive and therapeutic effects. This dietary approach corrects the whole-body glucose metabolism and restores the unbalanced metabolic substrate usage - by improving mitochondrial fuel oxidation - in the failing heart. In particular, biochemical, molecular, and genetic approaches suggest that renormalization of branched-chain amino acid oxidation in cardiac tissue, which is suppressed in HFrEF, plays a relevant role. Beyond the changes of systemic metabolism, cell-autonomous processes may explain at least in part the diet\'s cardioprotective impact.<br /><b>Conclusion</b><br />Collectively, these results suggest that manipulation of dietary amino acids, and especially essential amino acids, is a potential adjuvant therapeutic strategy to treat systolic dysfunction and HFrEF in humans.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Cardiovasc Res: 10 Jan 2023; epub ahead of print</small></div>
Ragni M, Greco CM, Felicetta A, Ren SV, ... Condorelli G, Nisoli E
Cardiovasc Res: 10 Jan 2023; epub ahead of print | PMID: 36626303
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<div><h4>Effect of Spironolactone on QRS Duration in Patients at Risk for Heart Failure (from the HOMAGE Trial).</h4><i>Ferreira JP, Cleland JGF, Girerd N, Pellicori P, ... Rossignol P, Zannad F</i><br /><AbstractText>The QRS duration can be easily obtained from a 12-lead electrocardiogram. Increased QRS duration reflects greater ventricular activation times and often ventricular dyssynchrony. Dyssynchrony causes an impairment of the global cardiac function and adversely affects the prognosis of patients with heart failure (HF). Little is known about the impact of pharmacologic therapies on the QRS duration, particularly for patients with presymptomatic HF with a preserved left ventricular (LV) ejection fraction (i.e., stage B HF with preserved ejection fraction [HFpEF]). The HOMAGE (Heart OMics in AGEing) trial enrolled patients at risk factors for developing HF and assigned them to receive either spironolactone or the usual care for approximately 9 months in a randomized manner. This analysis reports the effect of spironolactone on the QRS duration. A total of 525 patients was included in the analysis. The median (percentile<sub>25-75</sub>) QRS duration at baseline was 92 (84 to 106) ms. Spironolactone reduced the QRS duration at month 9 by -2.8, 95% confidence interval -4.6 to -1.0 ms, p = 0.003. No significant associations were found between month 9 changes in the QRS duration and corresponding changes in the LV ejection fraction, LV mass, LV end-diastolic volume, blood pressure, N-terminal pro-brain natriuretic peptide, and procollagen type I carboxy-terminal propeptide (all p >0.05). This analysis shows that for patients with stage B HFpEF, therapy with spironolactone for 9 months shortened the QRS duration, an effect that was not associated with reductions in LV mass or volume, supporting the hypothesis that spironolactone has direct beneficial effects to improve myocardial electrical activation in patients with stage B HFpEF.</AbstractText><br /><br />Copyright © 2022 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 10 Jan 2023; 191:39-42</small></div>
Ferreira JP, Cleland JGF, Girerd N, Pellicori P, ... Rossignol P, Zannad F
Am J Cardiol: 10 Jan 2023; 191:39-42 | PMID: 36634548
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<div><h4>Relationship between atrial fibrillation and a liver fibrogenesis marker in patients with acute heart failure.</h4><i>Miyamoto R, Nagao K, Matsuto K, Hata R, ... Sato Y, Inada T</i><br /><b>Background</b><br />Hemodynamic disturbance in heart failure (HF) induces extra-cardiac organ injury. Atrial fibrillation (AF) is common in patients with HF. The relationship between AF and organ injury in HF remains unclear. We investigated the relationship between AF and the liver fibrosis marker, type IV collagen 7S (P4NP 7S) in patients with HF.<br /><b>Methods and results</b><br />From a pooled dataset of 3 observational cohorts of hospitalized HF, 720 patients in whom P4NP 7S was measured before discharge were included. Median P4NP 7S were 5.1, 5.3, and 6.2 ng/mL in the sinus rhythm (SR) (n = 368), paroxysmal AF (n = 67), and persistent AF (n = 285) groups, respectively (P < 0.001). In the multiple linear regression analysis, the significant association with P4NP 7S was found for persistent AF (P < 0.001). The cumulative 1-year incidence of the primary composite endpoint of cardiac death and HF hospitalization were 27.6, 24.1, and 34.5% in the SR, paroxysmal AF, and persistent AF groups, respectively (Log-rank P = 0.07) and 25.3 and 34.5% in the low (below median) and high P4NP 7S groups, respectively (Log-rank P = 0.005). The adjusted risks of persistent AF versus SR and high P4NP 7S versus low P4NP 7S for the primary endpoint were 1.38 (95% confidence interval 1.02-1.89) and 1.52 (1.14-2.03), respectively. When patients were divided based on a combination of AF and P4NP 7S, concomitant persistent AF and high P4NP 7S portended a dismal prognosis.<br /><b>Conclusion</b><br />AF is associated with an increase in the liver fibrosis marker. Co-presence of persistent AF and P4NP 7S may portend adverse clinical outcomes.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Jan 2023; epub ahead of print</small></div>
Miyamoto R, Nagao K, Matsuto K, Hata R, ... Sato Y, Inada T
Int J Cardiol: 10 Jan 2023; epub ahead of print | PMID: 36638918
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<div><h4>Predictors of in-hospital heart failure in patients with acute anterior wall ST-segment elevation myocardial infarction.</h4><i>Liang J, Zhang Z</i><br /><b>Background</b><br />Heart failure (HF) is a severe complication of acute ST-segment elevation myocardial infarction (STEMI). Its incidence is associated with myocardial infarction location, and it occurs frequently after acute anterior wall STEMI due to the larger infarct size. However, predictors of in-hospital HF in patients with acute anterior wall STEMI are inadequately defined. We aimed to determine potential predictors of HF in patients with acute anterior wall STEMI during hospitalization.<br /><b>Methods</b><br />A total of 714 consecutive patients who were diagnosed with acute anterior wall STEMI and underwent primary percutaneous coronary intervention (pPCI) between January 2013 to August 2019 were enrolled retrospectively. We assigned the patients to HF and non-HF groups. The clinical parameters were subjected to univariate analysis and logistic regression analysis to obtain the independent predictors.<br /><b>Results</b><br />Among the 714 patients enrolled in the present study (mean age 61.0 ± 13.8 years, men 80.7%), 387 (54.2%) had in-hospital HF. According to a multivariate logistic regression analysis, ventricular fibrillation (VF, OR: 5.66, 95% CI: 2.25-14.23, P < 0.001) was the most striking independent predictor of in-hospital HF. Community-acquired pneumonia (CAP, OR: 4.72, 95% CI: 2.44-9.10, P < 0.001), age (OR: 1.03, 95% CI: 1.01-1.04, P < 0.001), left ventricular ejection fraction (LVEF, OR: 0.96, 95% CI: 0.93-0.97, P < 0.001), and peak N-terminal pro-brain natriuretic peptide (NT-pro-BNP, OR: 1.06, 95% CI: 1.02-1.11, P = 0.006) were also independently associated with in-hospital HF.<br /><b>Conclusion</b><br />VF, CAP, age, LVEF, and peak NT-pro-BNP were independently associated with in-hospital HF in patients with acute anterior wall STEMI.<br /><br />Copyright © 2023. Published by Elsevier B.V.<br /><br /><small>Int J Cardiol: 10 Jan 2023; epub ahead of print</small></div>
Liang J, Zhang Z
Int J Cardiol: 10 Jan 2023; epub ahead of print | PMID: 36638919
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<div><h4>Multiple Prior Live Births are Associated with Cardiac Remodeling and Heart Failure Risk in Women.</h4><i>Sarma AA, Paniagua SM, Lau ES, Wang D, ... Shah SJ, Ho JE</i><br /><b>Introduction</b><br />Greater parity has been associated with cardiovascular disease risk, though effects on cardiac remodeling and heart failure risk remain unclear.<br /><b>Methods</b><br />We examined the association of number of live births and echocardiographic measures of cardiac structure and function in participants of the Framingham Heart Study (FHS) using multivariable linear regression. We next examined the association of parity with incident heart failure with preserved (HFpEF) or reduced (HFrEF) ejection fraction using a Fine-Gray subdistribution hazards model in a pooled analysis of n=12,635 participants of FHS, the Cardiovascular Health Study, the Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular Endstage Disease. Secondary analyses included major CVD, MI, and stroke.<br /><b>Results</b><br />Among n=3931 FHS participants (mean age 48 ± 13 years), higher number of live births was associated with worse LV fractional shortening (multivariable β -1.11 (0.31), p= 0.0005 in ≥ 5 live births vs nulliparous women) and worse cardiac mechanics including global circumferential strain and longitudinal and radial dyssynchrony (p< 0.01 for all comparing ≥ 5 live births vs nulliparity). When examining HF subtypes, women with ≥5 live births were at higher risk of developing future HFrEF compared with nulliparous women (HR 1.93, 95% CI 1.19-3.12, p=0.008); by contrast, a lower risk of HFpEF was observed (HR 0.58, 95% CI 0.37-0.91, p=0.02).<br /><b>Conclusions</b><br />Greater number of live births are associated with worse cardiac structure and function. While there was no association with overall HF, a higher number of live births was associated with greater risk for incident HFrEF.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 10 Jan 2023; epub ahead of print</small></div>
Sarma AA, Paniagua SM, Lau ES, Wang D, ... Shah SJ, Ho JE
J Card Fail: 10 Jan 2023; epub ahead of print | PMID: 36638956
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<div><h4>Blood coagulation disorders in heart failure: from basic science to clinical perspectives.</h4><i>Siniarski A, Gąsecka A, Borovac J, Papakonstantinou PE, ... Guerreiro RA, Parker WAE</i><br /><AbstractText>Heart failure (HF) is a clinical syndrome divided into three subtypes, based on the left ventricular ejection fraction. Every subtype has specific clinical characteristics and concomitant diseases, substantially increasing risk of thromboembolic complications such as stroke, peripheral embolism and pulmonary embolism. Despite the annual prevalence of 1% and devastating clinical consequences, thromboembolic complications are not typically recognised as the leading problem in HF patients, representing an underappreciated clinical challenge. Although the currently available data do not support routine anticoagulation in patients with HF and sinus rhythm, initial reports suggest that such strategy might be beneficial in a subset of patients at especially high thromboembolic risk. Considering the existing evidence gap, we aimed to review the currently available data regarding coagulation disorders in acute and chronic HF based on the insight from preclinical and clinical studies, summarize the evidence regarding anticoagulation in HF in special case scenarios and outline future research directions to establish the optimal patient-tailored strategies for antiplatelet and anticoagulant therapy in HF. In summary, we highlight the top 10 pearls in the management of patients with HF and no other specific indications for oral anticoagulation therapy. Further studies are urgently needed to shed light on the pathophysiological role of platelet activation in HF and to evaluate whether antiplatelet or antithrombotic therapy could be beneficial in HF patients.</AbstractText><br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 09 Jan 2023; epub ahead of print</small></div>
Siniarski A, Gąsecka A, Borovac J, Papakonstantinou PE, ... Guerreiro RA, Parker WAE
J Card Fail: 09 Jan 2023; epub ahead of print | PMID: 36632933
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<div><h4>Assessment of Biomarkers of Myocardial injury, Inflammation, and Renal Function in Heart Failure with Reduced Ejection Fraction: The VICTORIA Biomarker Substudy.</h4><i>deFilippi CR, Alemayehu WG, Voors AA, Kaye D, ... O\'Connor CM, VICTORIA Study Group</i><br /><b>Background</b><br />Circulating biomarkers may be useful in understanding prognosis and treatment efficacy in heart failure with reduced ejection fraction (HFrEF). In the VICTORIA trial, vericiguat, a soluble guanylate cyclase (sGC) stimulator, reduced the primary outcome of cardiovascular death or HF hospitalization in HFrEF. We evaluated biomarkers of cardiac injury, inflammation, and renal function for associations with outcomes and vericiguat treatment effect.<br /><b>Methods</b><br />High-sensitivity cardiac troponin T (hs-cTnT), growth differentiation factor-15 (GDF-15), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and cystatin C were measured at baseline and 16 weeks. Associations of biomarkers with the primary outcome and its components were estimated. Interaction with study treatment was tested. Changes in biomarkers over time were examined by study treatment.<br /><b>Results</b><br />One or more biomarkers were measured in 4652 (92%) of 5050 participants at baseline and 4063 (81%) at 16 weeks. After adjustment, higher values of hs-cTnT, GDF-15, and IL-6 were associated with the primary outcome, independent of NT-proBNP. Higher hs-cTnT values were associated with a hazard ratio per log standard deviation of 1.21 (95% confidence interval 1.14-1.27). A treatment interaction with vericiguat was evident with hs-cTnT and cardiovascular death (p=0.04), but not HF hospitalization (p=0.38). All biomarkers except cystatin C declined over 16 weeks and no relationship between treatment assignment and changes in biomarker levels was observed.<br /><b>Conclusions</b><br />hs-cTnT, GDF-15, and IL-6 levels were associated with risk of the primary outcome in VICTORIA. Uniquely, lower hs-cTnT was associated with a lower rate of cardiovascular death but not HF hospitalization after treatment with vericiguat.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 09 Jan 2023; epub ahead of print</small></div>
deFilippi CR, Alemayehu WG, Voors AA, Kaye D, ... O'Connor CM, VICTORIA Study Group
J Card Fail: 09 Jan 2023; epub ahead of print | PMID: 36634811
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<div><h4>Circulating Angiokines are Associated with Reverse Remodeling and Outcomes in Chronic Heart Failure.</h4><i>Harrington J, Nixon AB, Daubert MA, Yow E, ... Felker GM, Karra R</i><br /><b>Background</b><br />We sought to determine whether circulating modifiers of endothelial function are associated with cardiac structure and clinical outcomes in patients with HFrEF.<br /><b>Methods</b><br />We measured 25 proteins related to endothelial function in 99 patients from the GUIDE-IT study. Protein levels were evaluated for association with echocardiographic parameters and the incidence of all-cause death and hospitalization for heart failure (HHF).<br /><b>Results</b><br />Higher concentrations of ANGPT2, VEGFR1 and HGF were significantly associated with worse function and larger ventricular volumes. Over time, decreases in ANGPT2 and, to a lesser extent, VEGFR1 and HGF, were associated with improvements in cardiac size and function. Individuals with higher concentrations of ANGPT2, VEGFR1, or HGF concentrations had an increased risk for a composite of death and HHF in the following year (HR 2.76 (95% CI 1.73 to 4.40) per 2-fold change in ANGPT2; HR 1.76 (95% CI 1.11 to 2.79) for VEGFR1; and HR 4.04 (95% CI 2.19 to 7.44) for HGF).<br /><b>Conclusions</b><br />Proteins related to endothelial function associate with cardiac size, cardiac function, and clinical outcomes in patients with HFrEF. These results support the concept that endothelial function may be an important contributor to the progression and recovery from HFrEF.<br /><br />Copyright © 2023. Published by Elsevier Inc.<br /><br /><small>J Card Fail: 08 Jan 2023; epub ahead of print</small></div>
Harrington J, Nixon AB, Daubert MA, Yow E, ... Felker GM, Karra R
J Card Fail: 08 Jan 2023; epub ahead of print | PMID: 36632934
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This program is still in alpha version.