Journal: Eur J Heart Fail

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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>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>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>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>Quantifying inflammation using Interleukin-6 for improved phenotyping and risk stratification in acute heart failure.</h4><i>Michou E, Wussler D, Belkin M, Simmen C, ... Breidthardt T, Mueller C</i><br /><b>Aims</b><br />Systemic inflammation may be central in the pathophysiology of acute heart failure (AHF). We aimed to assess the possible role of systemic inflammation in the pathophysiology, phenotyping, and risk stratification of patients with AHF.<br /><b>Methods and results</b><br />Using a novel Interleukin-6 immunoassay with unprecedented sensitivity (limit of detection 0.01ng/L) we quantified systemic inflammation in unselected patients presenting with acute dyspnea to the emergency department in a multicenter study. 1-year mortality was the primary prognostic endpoint. Among 2042 patients, 1026 (50.2%) had an adjudicated diagnosis of AHF, 83.7% of whom had elevated Interleukin-6 concentrations (>4.45ng/L). Interleukin-6 was significantly higher in AHF patients compared to patients with other causes of dyspnea (11.2 [6.1-26.5] ng/L vs 9.0 [3.2-32.3] ng/L, p<0.0005). Elevated Interleukin-6 concentrations were independently predicted by increasing NT-proBNP and high-sensitivity cardiac troponin T, as well as the clinical diagnosis of infection. Among the different AHF phenotypes, Interleukin-6 concentrations were highest in patients with cardiogenic shock (25.7 [14.0-164.2] ng/L) and lowest in patients with hypertensive AHF (9.3 [4.8-21.6] ng/L, p=0.001). Inflammation as quantified by Interleukin-6 was a strong and independent predictor of 1-year mortality both in all AHF patients, as well as those without clinically overt infection at presentation [adjusted hazard ratio (95%CI): 1.45 (1.15-1.83) vs 1.48 (1.09-2.00), respectively]. The addition of Interleukin-6 significantly improved the discrimination of the BIOSTAT-CHF risk score.<br /><b>Conclusion</b><br />An unexpectedly high percentage of patients with AHF have subclinical systemic inflammation as quantified by Interleukin-6, which seems to contribute to AHF phenotype and to the risk of death.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 04 Jan 2023; epub ahead of print</small></div>
Michou E, Wussler D, Belkin M, Simmen C, ... Breidthardt T, Mueller C
Eur J Heart Fail: 04 Jan 2023; epub ahead of print | PMID: 36597828
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<div><h4>NT-proBNP and High-Sensitivity Troponin T Hold Diagnostic Value in Cardiac Amyloidosis.</h4><i>Vergaro G, Castiglione V, Aimo A, Prontera C, ... Emdin M, Fontana M</i><br /><b>Aims</b><br />Cardiac amyloidosis (CA) is associated with an elevation of natriuretic peptides and troponins, predicting outcome. Nevertheless, the diagnostic yield of these biomarkers has not been extensively investigated. This study aimed to evaluate the diagnostic performance for CA of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT).<br /><b>Methods and results</b><br />Patients with suspected CA (n=1,149) underwent a diagnostic work-up in 3 Centers in Italy, France (n=343, derivation cohort), and United Kingdom (n=806, validation cohort). Biomarker values with either 100% sensitivity or ≥95% specificity were selected as rule-out/rule-in cut-offs, respectively. In the derivation cohort, 227 patients (66%) had CA, and presented with higher NT-proBNP and hs-TnT. NT-proBNP 180 ng/L and hs-TnT 14 ng/L were selected as rule-out cut-offs, and hs-TnT 86 ng/L as rule-in cut-off. NT-proBNP <180 ng/L or hs-TnT <14 ng/L were found in 7% of patients, ruled out without false negatives. In the validation cohort, 20% of patients (2% false negatives) had NT-proBNP <180 ng/L or hs-TnT <14 ng/L, and 10% showed both biomarkers below cut-offs (0.5% false negatives). These cut-offs refined CA prediction when added to echocardiographic scores in patients with a hematologic disease or an increased wall thickness. In the validation cohort, the 86 ng/L hs-TnT cut-off ruled in 20% of patients (2% false positives). NT-proBNP and hs-TnT cut-offs retained their rule-out and rule-in performance also in cohorts with CA prevalence of 20%, 10%, 5% and 1% derived from the original cohort through bootstrap analysis.<br /><b>Conclusions</b><br />Cardiac biomarkers can refine the diagnostic algorithm in patients with suspected CA. NT-proBNP <180 ng/L and hs-TnT <14 ng/L reliably exclude the diagnosis, both in the overall population and subgroups referred for either AL-CA or cardiac (pseudo)hypertrophy.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 04 Jan 2023; epub ahead of print</small></div>
Vergaro G, Castiglione V, Aimo A, Prontera C, ... Emdin M, Fontana M
Eur J Heart Fail: 04 Jan 2023; epub ahead of print | PMID: 36597836
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<div><h4>Transcatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation with 3 Generation Devices in Heart Failure Patients-Results from the Global EXPAND Post-Market Study.</h4><i>Orban M, Rottbauer W, Williams M, Mahoney P, ... Kar S, Hausleiter J</i><br /><b>Aims</b><br />Mitral valve transcatheter edge-to-edge repair (M-TEER) is a guideline-recommended treatment option for patients with secondary mitral regurgitation (SMR). The purpose of this analysis is to report contemporary real-world outcomes in SMR patients treated with 3<sup>rd</sup> generation MitraClip systems.<br /><b>Methods and results</b><br />EXPAND is a prospective, multi-center, international, single arm study with 1041 patients treated for MR with MitraClip NTR/XTR, with 30-day and 1-year follow-up (FU). All echocardiograms were analyzed by an independent echocardiographic core lab. Study outcomes included: procedural outcomes, durability of MR reduction, and major adverse events including all-cause mortality and hospitalizations for heart failure (HFH). A subgroup of 413 symptomatic patients (age 74.7±10.1 years, 58% male) with severe SMR were included. MR reduction to MR≤1+ and MR≤2+ was achieved in 93.0% and 98.5% of patients, respectively, which was sustained at 1-year-FU. All-cause mortality was 17.7% at 1-year-FU, and the combined endpoint of all-cause mortality or 1<sup>st</sup> HFH occurred in 34% of patients. This combined endpoint was significantly less frequently observed in MR≤1+ patients (Kaplan-Maier-estimates: 29.7% vs. 69.9% for MR≤1+ vs. MR≤2+; p<0.0001). NYHA functional class improved significantly from baseline (NYHA≤II:17%) to 1-year-FU (NYHA≤II:78%) (p<0.0001). While MR reduction was comparable between NTR-only vs. XTR-only treated patients, less XTR clips were required for achieving MR reduction.<br /><b>Conclusions</b><br />Under real-world conditions, optimal sustained MR reduction to MR≤1+ was achieved in a high percentage of patients with 3<sup>rd</sup> generation MitraClip, which translated into symptomatic improvement and low event rates. These results appear to be comparable with recent randomized clinical trials. 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: 04 Jan 2023; epub ahead of print</small></div>
Orban M, Rottbauer W, Williams M, Mahoney P, ... Kar S, Hausleiter J
Eur J Heart Fail: 04 Jan 2023; epub ahead of print | PMID: 36597850
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<div><h4>Biomarker signature and pathophysiological pathways in chronic heart failure patients with metabolic syndrome.</h4><i>van der Hoef CCS, Boorsma EM, Emmens JE, van Essen BJ, ... Lam CSP, Voors AA</i><br /><b>Aim</b><br />The comorbidities that collectively define metabolic syndrome are common in patients with heart failure. However, the role of metabolic syndrome in the pathophysiology of heart failure is not well understood. We therefore investigated the clinical and biomarker correlates of metabolic syndrome in patients with heart failure.<br /><b>Methods</b><br />In 1103 patients with heart failure, we compared the biomarker expression using a panel of 363 biomarkers among patients with (n = 468[42%]) and without (n = 635[58%]) metabolic syndrome. Subsequently, a pathway overrepresentation analysis was performed to identify key biological pathways. Findings were validated in an independent cohort of 1433 patients with heart failure of whom 615 (43%) had metabolic syndrome. Metabolic syndrome was defined as the presence of ≥ three of five criteria, including central obesity, elevated serum triglycerides, reduced high-density lipoprotein cholesterol, insulin resistance and hypertension.<br /><b>Results</b><br />The most significantly elevated biomarkers in patients with metabolic syndrome were leptin (log2 fold change 0.92,P = 5.85 × 10<sup>-21</sup> ), fatty acid-binding protein 4 (log2 fold change 0.61,P = 1.21 × 10<sup>-11</sup> ), interleukin-1 receptor antagonist (log2 fold change 0.47,P = 1.95 × 10<sup>-13</sup> ), tumour necrosis factor receptor superfamily member 11a (log2 fold change 0.35,P = 4.16 × 10<sup>-9</sup> ), and RET proto-oncogene (log2 fold change 0.31,P = 4.87 × 10<sup>-9</sup> ). Network analysis identified 10 pathways in the index cohort and 6 in the validation cohort, all related to inflammation. The primary overlapping pathway in both the index and validation cohort was up-regulation of the natural killer cell-mediated cytotoxicity pathway.<br /><b>Conclusion</b><br />Metabolic syndrome is highly prevalent in heart failure and is associated with biomarkers and pathways relating to obesity, lipid metabolism and immune responses underlying chronic inflammation. 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: 04 Jan 2023; epub ahead of print</small></div>
van der Hoef CCS, Boorsma EM, Emmens JE, van Essen BJ, ... Lam CSP, Voors AA
Eur J Heart Fail: 04 Jan 2023; epub ahead of print | PMID: 36597718
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<div><h4>Efficacy of omecamtiv mecarbil in heart failure with reduced ejection fraction according to N-terminal pro-B-type natriuretic peptide level: Insights from the GALACTIC-HF trial.</h4><i>Docherty KF, McMurray JJV, Claggett BL, Miao ZM, ... Meng L, Teerlink JR</i><br /><b>Background</b><br />N-terminal pro-B-type natriuretic peptide (NT-proBNP) is predictive of both outcomes and response to treatment in patients with heart failure with reduced ejection fraction (HFrEF).<br /><b>Objective</b><br />To examine the effect of the cardiac myosin activator omecamtiv mecarbil according to baseline NT-proBNP level in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure trial (GALACTIC-HF).<br /><b>Methods</b><br />The primary outcome was the composite of a worsening HF event (urgent clinic visit, emergency department visit, or hospitalization) or cardiovascular death. We prespecified analysis of the effect of treatment according to baseline NT-proBNP (≤median, >median), excluding individuals with AF/AFL.<br /><b>Results</b><br />Of the 8232 patients analyzed, 8206 had an available baseline NT-proBNP measurement. Among the 5971 patients not in AF/AFL, the median (Q1, Q3) NT-proBNP level was 1675 (812-3579) pg/ml. Hazard ratios (HR) for the effect of omecamtiv mecarbil, compared with placebo, for the primary endpoint in patients without AF/AFL were: ≤median 0.94 (95% CI, 0.80-1.09), >median 0.81 (0.73-0.90) [P-interaction = 0.095]; for the overall population (including patients with AF/AFL) the HRs were ≤ median 1.01 (0.90-1.15) and > median 0.88 (0.80-0.96) [P-interaction = 0.035]. There was an interaction between treatment and NT-proBNP, examined as a continuous variable, with greater effect of omecamtiv mecarbil on the primary outcome in patients with a higher baseline NT-proBNP (P-interaction = 0.086).<br /><b>Conclusions</b><br />In GALACTIC-HF, the benefit of omecamtiv mecarbil appeared to be larger in patients with higher baseline NT-proBNP levels, especially in patients without AF/AFL. 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: 04 Jan 2023; epub ahead of print</small></div>
Docherty KF, McMurray JJV, Claggett BL, Miao ZM, ... Meng L, Teerlink JR
Eur J Heart Fail: 04 Jan 2023; epub ahead of print | PMID: 36597719
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<div><h4>Bridging Strategies and Cardiac Replacement Outcomes in Patients with Acute Decompensated Heart Failure-Related Cardiogenic Shock.</h4><i>Varshney AS, Berg DD, Zhou G, Sinnenberg L, ... Rinewalt D, Givertz MM</i><br /><b>Aims</b><br />To describe outcomes associated with bridging strategies in patients with acute decompensated heart failure-related cardiogenic shock (ADHF-CS) bridged to durable left ventricular assist device (LVAD) or heart transplant (HTx).<br /><b>Methods and results</b><br />Durable LVAD or HTx recipients from 2014 to 2019 with pre-operative ADHF-CS were identified in the Society of Thoracic Surgeons Adult Cardiac Surgery Database and stratified by bridging strategy. The primary outcome was operative or 30-day post-operative mortality. Secondary outcomes included post-operative major bleeding. Exploratory comparisons between bridging strategies and outcomes were performed using overlap weighting with and without covariate adjustment. Among 9783 patients with pre-operative CS, 8777 (89.7%) had ADHF-CS. Medical therapy (N = 5013) was the most common bridging strategy, followed by intra-aortic balloon pump (IABP; N = 2816), catheter-based temporary mechanical circulatory support (TMCS; N = 417), and veno-arterial extracorporeal membrane oxygenation (VA-ECMO; N = 465). Mortality was highest in patients bridged with VA-ECMO (22%), followed by catheter-based TMCS (10%), IABP (9%), and medical therapy (7%). Adverse post-operative outcomes were more frequent in LVAD recipients compared with HTx recipients.<br /><b>Conclusion</b><br />Among patients with ADHF-CS bridged to HTx or durable LVAD, the highest rates of death and adverse events during index hospitalization were observed in those bridged with VA-ECMO, followed by catheter-based TMCS, IABP, and medical therapy. Patients who received durable LVAD had higher rates of post-operative complications compared with HTx recipients. Prospective trials are needed to define optimal bridging strategies in patients with ADHF-CS. 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: 04 Jan 2023; epub ahead of print</small></div>
Varshney AS, Berg DD, Zhou G, Sinnenberg L, ... Rinewalt D, Givertz MM
Eur J Heart Fail: 04 Jan 2023; epub ahead of print | PMID: 36597721
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<div><h4>Peri-procedural management of transcatheter mitral valve replacement in patients with heart failure.</h4><i>Hungerford SL, Dahle G, Duncan A, Hayward CS, Muller DW</i><br /><AbstractText>Over the past decade, transcatheter mitral valve replacement (TMVR) technologies have evolved with the objective of improving outcomes for patients with severe mitral regurgitation (MR) deemed unsuitable for conventional mitral valve (MV) surgery. Although the safety and efficacy of transcatheter mitral valve edge-to-edge repair (TEER) is well-established, there is a sense amongst innovators that a major advantage of TMVR may be to offer a more complete solution for the correction of MR in patients whose complex anatomy means that the likelihood of achieving grade 0 or 1 MR with TEER is low. However, abrupt correction of MR in a poorly prepared left ventricle poses a number of unique hemodynamic challenges, particularly when sudden elimination of regurgitant flow causes a relative increase in left ventricular (LV) afterload. Rapid reduction in LV cavity size following MR elimination may itself result in relative LV outflow tract obstruction (LVOTO), irrespective of the intrinsic risk of LVOTO associated with TMVR. Nevertheless, TMVR on a beating heart affords the opportunity to study real-time invasive cardiac indices in high-risk patients with acute reversal of severe MR . 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: 15 Dec 2022; epub ahead of print</small></div>
Hungerford SL, Dahle G, Duncan A, Hayward CS, Muller DW
Eur J Heart Fail: 15 Dec 2022; epub ahead of print | PMID: 36519634
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<div><h4>Normal and excessive muscle sympathetic nerve activity in heart failure: implications for future trials of therapeutic autonomic modulation.</h4><i>Badrov MB, Keir DA, Tomlinson G, Notarius CF, ... Keys E, Floras JS</i><br /><b>Aims</b><br />Patients with sympathetic excess are those most likely to benefit from novel interventions targeting the autonomic nervous system. To inform such personalized therapy, we identified determinants of augmented muscle sympathetic nerve activity (MSNA) in heart failure, versus healthy controls.<br /><b>Methods and results</b><br />We compared data acquired in 177 conventionally-treated, stable non-diabetic patients in sinus rhythm, aged 18-79 years (149 males; 28 females; LVEF: 25±11% [mean±SD]; range 5-60%), and, concurrently, under similar conditions, in 658 healthy, normotensive volunteers (398 males; 260 females; aged 18-81 years). In heart failure, MSNA ranged between 7 and 90 bursts·min<sup>-1</sup> , proportionate to heart rate (P<0.0001) and body mass index (BMI) (P=0.03), but was unrelated to age, blood pressure, or drug therapy. Mean MSNA, adjusted for age, sex, BMI, and heart rate, was greater in heart failure (+14.2 bursts·min<sup>-1</sup> ; 95% CI, 12.1-16.3; P<0.0001), but lower in women (-5.0 bursts·min<sup>-1</sup> ; 95% CI, 3.4-6.6; P<0.0001). With spline modeling, LVEF accounted for 9.8% of MSNA variance; MSNA related inversely to LVEF below an inflection point of ~21% (P<0.006), but not above. Burst incidence was greater in ischemic than dilated cardiomyopathy (P=0.01), and patients with sleep apnea (P=0.03). Burst frequency correlated inversely with stroke volume (P<0.001), cardiac output (P<0.001), and V̇O<sub>2</sub> peak (P=0.002), and directly with norepinephrine (P<0.0001) and peripheral resistance (P<0.001).<br /><b>Conclusion</b><br />Burst frequency and incidence exceeded normative values in only ~53% and ~33% of patients. Such diversity encourages selective deployment of sympatho-modulatory therapies. Clinical characteristics can highlight individuals who may benefit from future personalized interventions targeting pathological sympathetic activation.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 02 Dec 2022; epub ahead of print</small></div>
Badrov MB, Keir DA, Tomlinson G, Notarius CF, ... Keys E, Floras JS
Eur J Heart Fail: 02 Dec 2022; epub ahead of print | PMID: 36459000
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<div><h4>Sex differences among patients with transthyretin amyloid cardiomyopathy - from diagnosis to prognosis.</h4><i>Patel RK, Ioannou A, Razvi Y, Chacko L, ... Gillmore JD, Fontana M</i><br /><b>Aims</b><br />Transthyretin amyloid cardiomyopathy (ATTR-CM) is predominantly diagnosed in men. The few available studies suggest affected women have a more favourable cardiac phenotype. We aimed to characterize sex differences among consecutive patients with non-hereditary and two prevalent forms of hereditary (h)ATTR-CM diagnosed over a 20-year period.<br /><b>Methods and results</b><br />Analysis of deep phenotyping at presentation, changes on serial echocardiography and overall prognosis were evaluated. In total, 1732 consecutive patients were studied, comprising: 1095 with wild-type (wt)ATTR-CM; 206 with T60A-hATTR-CM; and 431 with V122I-hATTR-CM. Female prevalence was greater in T60A-hATTR-CM (29.6%) and V122I-hATTR-CM (27.8%) compared to wtATTR-CM (6%). At presentation, females were 3.3 years older than males (wtATTR-CM: 81.9 vs. 77.8 years; T60A-hATTR-CM: 68.7 vs. 65.1 years; V122I-hATTR-CM: 77.1 vs. 74.9 years). Body size significantly influenced measures of disease severity; when indexed, overall structural and functional phenotype was similar between sexes, the few significant differences suggested a mildly worse phenotype in females. No significant differences were observed in both disease progression on serial echocardiography and mortality across the overall population (p = 0.459) and when divided by genotype (wtATTR-CM: p = 0.730; T60A-hATTR-CM: p = 0.161; V122I-hATTR-CM: p = 0.056).<br /><b>Conclusion</b><br />This study of a well-characterized large cohort of ATTR-CM patients did not demonstrate overall differences between sexes in either clinical phenotype, when indexed, or with respect to disease progression and prognosis. Non-indexed wall thickness measurements may have contributed to both under-representation and delays in diagnosis for affected females and highlights the potential role of utilizing indexed echocardiographic parameters for a more accurate assessment of patients at diagnosis and for disease prognostication.<br /><br />© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.<br /><br /><small>Eur J Heart Fail: 01 Dec 2022; 24:2355-2363</small></div>
Patel RK, Ioannou A, Razvi Y, Chacko L, ... Gillmore JD, Fontana M
Eur J Heart Fail: 01 Dec 2022; 24:2355-2363 | PMID: 36575133
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<div><h4>Central Hemodynamic Abnormalities and Outcome in Patients with Unexplained Dyspnea.</h4><i>Omote K, Verbrugge FH, Sorimachi H, Omar M, ... Reddy YNV, Borlaug BA</i><br /><b>Aims</b><br />Little data is available regarding prognostic implications of Invasive exercise testing in heart failure (HF) with preserved ejection fraction (HFpEF). The present study aimed to investigate whether rest/exercise central hemodynamic abnormalities are associated with adverse clinical outcomes.<br /><b>Methods and results</b><br />Patients with exertional dyspnea and EF≥50% (n=764) underwent invasive exercise testing and follow-up for HF hospitalization or death. There were 117 patients with events over a median follow-up of 2.7 (IQR 0.5-4.6) years. Among patients with normal resting PAWP (<15mmHg, n=380 [50%]), increased exercise PAWP (≥25mmHg, n= 187 [24%]) was associated with 2.4-fold higher risk of events compared to those with normal exercise PAWP (<25mmHg, n= 193 [25%]) (HR 2.44; 95%CI, 1.11-5.36; p=0.03), while patients with elevated resting PAWP (≥15mmHg, n=384 [50%]) displayed even higher risk compared to HFpEF with normal resting PAWP (HR 2.24; 95%CI, 1.38-3.65; p=0.001). Similar findings were observed for rest/exercise right atrial pressure, and rest/exercise pulmonary artery pressures. Higher peak VO<sub>2</sub> was associated with decreased risk of events, and this relationship was solely explained by exercise cardiac output. In a multivariable-adjusted Cox model, each 1 SD increase in exercise PAWP was associated with a 41% greater hazard of events (HR 1.41 [95% CI: 1.13-1.76]; p=0.002), while each 1 SD decrease in exercise CO was associated with a 37% increased risk (HR 0.63 [95% CI: 0.47-0.83]; p=0.001).<br /><b>Conclusions</b><br />Hemodynamic abnormalities currently used for diagnosis of HFpEF are associated with increased risk for adverse events. Treatments that reduce central pressures while improving cardiac output reserve may offer greatest benefit to improve outcomes in HFpEF.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 24 Nov 2022; epub ahead of print</small></div>
Omote K, Verbrugge FH, Sorimachi H, Omar M, ... Reddy YNV, Borlaug BA
Eur J Heart Fail: 24 Nov 2022; epub ahead of print | PMID: 36420788
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<div><h4>Effects of haemodynamically atrio-ventricular optimized His-pacing on heart failure symptoms and exercise capacity: The His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) randomised, double-blind, cross-over trial.</h4><i>Whinnett ZI, Shun-Shin MJ, Tanner M, Foley P, ... Cleland JG, Keene D</i><br /><b>Aims</b><br />Excessive prolongation of PR interval impairs coupling of AV contraction, which reduces left ventricular pre-load and stroke volume, and worsens symptoms. His-bundle pacing allows AV-delay shortening while maintaining normal ventricular activation. HOPE-HF evaluated whether AV-optimized His pacing is preferable to no-pacing, in double-blind cross-over fashion, in patients with heart failure, left ventricular ejection fraction (LVEF) ≤40%, PR interval ≥200ms and either QRS ≤140ms or right BBB.<br /><b>Methods and results</b><br />Patients had atrial and His-bundle leads implanted (and an ICD lead if clinically indicated) and were randomized, to 6-months of pacing and 6-months of no-pacing utilizing a cross-over design. The primary outcome was peak oxygen uptake during symptom-limited exercise. Quality of life, LVEF and patients\' holistic symptomatic preference between arms were secondary outcomes. 167 patients were randomized: 90% men, 69±10 years, QRS duration 124±26ms, PR interval 249±59ms, LVEF 33±9%. Neither peak VO<sub>2</sub> (+0.25 ml/min/kg, 95% CI -0.23 to +0.73, p=0.3) nor LVEF (+0.5%, 95% CI -0.7 to 1.6, p=0.4) changed with pacing but Minnesota Living with Heart Failure quality of life improved significantly (-3.7, 95% CI -7.1 to -0.3, p=0.03). 76% of patients preferred His-bundle pacing-on and 24% pacing-off (p<0.0001).<br /><b>Conclusion</b><br />His-bundle pacing did not increase peak oxygen uptake but, under double-blind conditions, significantly improved quality of life and was symptomatically preferred by the clear majority of patients. Ventricular pacing delivered via the His bundle did not adversely impact ventricular function during the 6 months. 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: 20 Nov 2022; epub ahead of print</small></div>
Abstract
<div><h4>Sequencing and Titrating Approach of Therapy in Heart Failure with Reduced Ejection Fraction Following the 2021 ESC guidelines: an International Cardiology Survey.</h4><i>Fauvel C, Bonnet G, Mullens W, Giraldo CIS, ... Roubille F, Mewton N</i><br /><b>Aims</b><br />In symptomatic patients with heart failure and reduced ejection fraction (HFrEF), recent international guidelines recommend initiating four major therapeutic classes rather than sequential initiation. It remains unclear how this change in guidelines is perceived by practicing cardiologists versus heart failure (HF) specialists.<br /><b>Methods and results</b><br />An independent academic web-based survey was designed by a group of HF specialists and posted by email and through various social networks to a broad community of cardiologists worldwide one year after the publication of the latest European HF guidelines. Six hundred and fifteen cardiologists (38 [32, 47] years old, 63% males) completed the survey, of which 58% were working in a university hospital and 26% were HF specialists. The threshold to define HFrEF was ≤40% for 61% of the physicians. Preferred drug prescription for the sequential approach was angiotensin-converting enzyme inhibitors or angiotensin receptor-neprilysin inhibitors first (74%), betablockers second (55%), mineralocorticoid receptor antagonists third (52%), and sodium-glucose transporter 2 inhibitors (53%) fourth. Eighty-four percent of participants felt that starting all four classes was feasible within the initial hospitalization, and 58% felt that titration is less important than introducing a new class. Age, status in training, and specialization in HF field were the principal characteristics that significantly impacted the answers.<br /><b>Conclusion</b><br />In a broad international cardiology community, the \"historical approach\" for HFrEF therapies remains the preferred sequencing approach. However accelerated introduction and up-titration are also major treatment goals. Strategy trials in treatment guidance are needed to further change practices. 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: 20 Nov 2022; epub ahead of print</small></div>
Fauvel C, Bonnet G, Mullens W, Giraldo CIS, ... Roubille F, Mewton N
Eur J Heart Fail: 20 Nov 2022; epub ahead of print | PMID: 36404398
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<div><h4>Effect of beta-blocker therapy on the response to mavacamten in patients with symptomatic obstructive hypertrophic cardiomyopathy.</h4><i>Wheeler MT, Jacoby D, Elliott PM, Saberi S, ... Li W, Olivotto I</i><br /><b>Aims</b><br />In the EXPLORER-HCM trial, mavacamten improved exercise capacity and symptoms in patients with obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten effects on the primary endpoint, a composite of peak oxygen consumption (VO<sub>2</sub> ) and New York Heart Association (NYHA) class, were greater in patients not receiving background beta-blockers than in those receiving beta-blockers. We sought to determine if the effect of background treatment was consistent across other clinically meaningful parameters.<br /><b>Methods and results</b><br />Subgroup analyses by beta-blocker use were performed in patients with oHCM from the EXPLORER-HCM and mavacamten long-term extension (MAVA-LTE) studies. In EXPLORER-HCM, 189 patients (75.3%) were receiving beta-blockers, and 62 (24.7%) were receiving non-dihydropyridine calcium-channel blockers or no background HCM medication; 170 patients (90.4%) receiving beta-blockers had chronotropic incompetence. Improvements in peak VO<sub>2</sub> at week 30 with mavacamten versus placebo were lower with beta-blockers (mean difference [95% confidence interval (CI)]: 1.04 [0.12, 1.95] mL/kg/min) than without beta-blockers (mean difference [95% CI]: 2.69 [1.29, 4.09] mL/kg/min); improvements in non-heart rate-dependent parameters (V<sub>E</sub> /VCO<sub>2</sub> slope) appeared unaffected by beta-blockers. Improvements in functional capacity parameters at week 30 with mavacamten versus placebo were independent of beta-blockade for post-exercise left ventricular outflow tract gradient (mean difference [95% CI]: -37.9 [-48.0, -27.9] mmHg with beta-blockers; -33.5 [-53.6, -13.3] mmHg without beta-blockers), proportion of patients with reduction of ≥1 NYHA class, Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores and NT-proBNP. Mavacamten benefits were reproduced and maintained in MAVA-LTE regardless of beta-blockade.<br /><b>Conclusion</b><br />Mavacamten improved measures of functional capacity, LVOT obstruction, symptom burden and biomarkers in patients with HCM regardless of beta-blocker use. Beta-blocker use was often associated with chronotropic incompetence, affecting peak VO<sub>2</sub> and other heart rate-dependent measures, but had minimal impact on heart-rate independent measures. 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: 20 Nov 2022; epub ahead of print</small></div>
Wheeler MT, Jacoby D, Elliott PM, Saberi S, ... Li W, Olivotto I
Eur J Heart Fail: 20 Nov 2022; epub ahead of print | PMID: 36404399
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<div><h4>β3-adrenergic agonist treatment in chronic pulmonary hypertension associated with heart failure (SPHERE-HF): a double blind, placebo-controlled, randomized clinical trial.</h4><i>García-Álvarez A, Blanco I, García-Lunar I, Jordà P, ... Ibañez B, SPHERE-HF investigators</i><br /><b>Background:</b><br/>and aims</b><br />Pulmonary hypertension (PH) associated with left heart disease is an increasingly prevalent problem, orphan of targeted therapies, and related to a poor prognosis, particularly when pre and postcapillary PH combine. The current study aimed to determine whether treatment with the selective β3 adrenoreceptor agonist mirabegron improves outcomes in patients with combined pre and postcapillary PH.<br /><b>Methods and results</b><br />The β3 Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure (SPHERE-HF) trial is a multicenter, randomized, parallel, placebo-controlled clinical trial that enrolled stable patients with combined pre and postcapillary PH (CpcPH) associated with symptomatic HF. A total of 80 patients were assigned to receive mirabegron (50 mg daily, titrated till 200 mg daily, n=39) or placebo (n=41) for 16 weeks. Of them, 66 patients successfully completed the study protocol and were valid for the main analysis. The primary endpoint was the change in pulmonary vascular resistance (PVR) on right heart catheterization. Secondary outcomes included the change in right ventricular (RV) ejection fraction by cardiac magnetic resonance or computed tomography, other hemodynamic variables, functional class, and quality of life. The trial was negative for the primary outcome (placebo-corrected mean difference of 0.62 Wood units, 95%CI -0.38, 1.61 WU, p=0.218). Patients receiving mirabegron presented a significant improvement in RV ejection fraction as compared to placebo (placebo-corrected mean difference of 3.0%, 95%CI 0.4, 5.7%, p=0.026), without significant differences in other pre-specified secondary outcomes.<br /><b>Conclusions</b><br />SPHERE-HF is the first clinical trial to assess the potential benefit of β3 adrenergic agonists in PH. The trial was negative since mirabegron did not reduce PVR, the primary endpoint, in patients with CpcPH. On pre-specified secondary outcomes, a significant improvement in RV ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life. 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: 20 Nov 2022; epub ahead of print</small></div>
García-Álvarez A, Blanco I, García-Lunar I, Jordà P, ... Ibañez B, SPHERE-HF investigators
Eur J Heart Fail: 20 Nov 2022; epub ahead of print | PMID: 36404400
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<div><h4>The Effects of Mineralocorticoid Receptor Antagonists on Cardiovascular Outcomes in Patients With End-Stage Renal Disease and Heart Failure.</h4><i>Lin DS, Lin FI, Lin YS, Lee JK, Lin YH</i><br /><b>Objectives</b><br />To evaluate the effects of mineralocorticoid receptor antagonists (MRAs) on cardiovascular outcomes in patients with heart failure under maintenance dialysis in a real-world setting.<br /><b>Background</b><br />MRAs have been shown to provide survival benefits in patients with heart failure; however, MRA use in patients with chronic kidney disease has been limited by safety concerns. The effects of MRAs on outcomes in patients with end-stage renal disease (ESRD) and heart failure remain unknown.<br /><b>Methods</b><br />A retrospective cohort study was conducted by collecting data from the Taiwan National Health Insurance Research Database (NHIRD). Patients diagnosed with heart failure and ESRD and who started maintenance dialysis between January 1, 2001, and December 31, 2013, were identified. Patients were grouped according to MRA prescription. The outcomes of interest included cardiovascular death (CV death), hospitalization for heart failure (HHF), all-cause mortality, acute myocardial infarction (AMI), ischemic stroke, any coronary revascularization procedures, and new-onset hyperkalemia. Propensity score matching was performed at a 1:3 ratio between MRA users and non-users to minimize selection bias.<br /><b>Results</b><br />A total of 50,872 patients who satisfied our inclusion and exclusion criteria were identified. After 1:3 matching, 2,176 patients were included in the MRA group, and 6,528 patients were included in the non-MRA group. The risk of CV death was significantly lower among patients who received MRAs than those who did not (hazard ratio [HR] 0.88, 95% confidence interval [95% CI] 0.80-0.95), as was the risk of all-cause mortality (HR 0.88, 95% CI 0.83-0.94). Reductions in the risks of CV death and all-cause mortality were more prominent among patients undergoing hemodialysis and those with coronary artery disease.<br /><b>Conclusions</b><br />In patients undergoing regular dialysis who are diagnosed with heart failure, the use of MRAs is associated with lower risks of all-cause mortality and CV death. The benefits of MRA treatment in heart failure may persist in patients with ESRD. Further investigations through randomized controlled trials are needed to assess the efficacy and safety of MRAs in this high-risk population. 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: 20 Nov 2022; epub ahead of print</small></div>
Lin DS, Lin FI, Lin YS, Lee JK, Lin YH
Eur J Heart Fail: 20 Nov 2022; epub ahead of print | PMID: 36404402
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<div><h4>Incidence and Clinical Correlates of De-novo Aortic Regurgitation with a Fully Magnetically Levitated LVAD: A MOMENTUM3 Trial Portfolio Analysis.</h4><i>Uriel N, Milano C, Agarwal R, Lee S, ... Crandall D, Mehra MR</i><br /><b>Aims</b><br />We assessed the incidence, predictors and clinical correlates of Aortic Regurgitation (AR), which physiologically reduces left ventricular assist device (LVAD) effectiveness due to recirculation syndrome, in the MOMENTUM 3 trial portfolio of the fully magnetically levitated HM3 pump using the pivotal randomized trial (PT) and post-approval continued access protocol (CAP).<br /><b>Methods and results</b><br />AR incidence at 2-years was analyzed in the randomized PT and validated in the first 1000 implanted patients of the CAP. Patients with concomitant/prior aortic valve surgery or without baseline or post-implant echocardiograms were excluded from this analysis. AR severity was assessed qualitatively by site-adjudicated echocardiograms (Significant AR was defined as moderate or severe grade on echocardiogram). Of 1028 patients enrolled in the PT, 918 were eligible for inclusion in this analysis (HM3=465, HMII=453). At 2-years of LVAD support, freedom from significant AR was greater in the HM3 (92%) than HMII (82%) (HR 0.45, 95% CI 0.27-0.75, p<0.01). Of 907 patients analyzed from the first 1000 implanted CAP patients, the rate of freedom from significant AR was 90%, consistent with the PT (P=0.3). In the combined HM3 group (n=1372) multivariable cox modeling identified increasing age and female sex as significant predictors. Survival free of urgent transplant or AR corrective procedure was similar between HM3 patients with and without significant de-novo AR.<br /><b>Conclusions</b><br />The development of moderate or severe grade de-novo AR is reduced with the fully magnetically levitated HM3 LVAD compared to the axial-flow HMII pump. This lower rate of significant de-novo AR with the HM 3 pump is not associated with a worse outcome at 2-years of follow-up. 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: 20 Nov 2022; epub ahead of print</small></div>
Uriel N, Milano C, Agarwal R, Lee S, ... Crandall D, Mehra MR
Eur J Heart Fail: 20 Nov 2022; epub ahead of print | PMID: 36404406
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<div><h4>Connecting Epicardial Adipose Tissue and Heart Failure with Preserved Ejection Fraction: Mechanisms, Management and Modern Perspectives.</h4><i>van Woerden G, van Veldhuisen DJ, Westenbrink BD, de Boer RA, Rienstra M, Gorter TM</i><br /><AbstractText>Obesity is very common in patients with heart failure with preserved ejection fraction (HFpEF) and it has been suggested that obesity plays an important role in the pathophysiology of this disease. While body mass index defines the presence of obesity, this measure provides limited information on visceral adiposity, which is probably more relevant in the pathophysiology of HFpEF. Epicardial adipose tissue is the visceral fat situated directly adjacent to the heart and recent data demonstrate that accumulation of epicardial adipose tissue is associated with the onset, symptomatology and outcome of HFpEF. However, the mechanisms by which epicardial adipose tissue may be involved in HFpEF remain unclear. It is also questioned whether epicardial adipose tissue may be a specific target for therapy for this disease. In the present review, we describe the physiology of epicardial adipose tissue and the pathophysiological transformation of epicardial adipose tissue in response to chronic inflammatory diseases, and we postulate conceptual mechanisms on how epicardial adipose tissue may be involved in HFpEF pathophysiology. Lastly, we outline potential treatment strategies, knowledge gaps and directions for further research. 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: 17 Nov 2022; epub ahead of print</small></div>
van Woerden G, van Veldhuisen DJ, Westenbrink BD, de Boer RA, Rienstra M, Gorter TM
Eur J Heart Fail: 17 Nov 2022; epub ahead of print | PMID: 36394512
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<div><h4>Health-Related Quality of Life Outcomes in PARAGON-HF.</h4><i>Chandra A, Polanczyk CA, Claggett BL, Vaduganathan M, ... Solomon SD, Lewis EF</i><br /><b>Aims</b><br />Heart failure (HF) is associated with poor health-related quality of life (HRQL). Patients with HF with preserved ejection fraction (HFpEF) have similar HRQL impairment as those with reduced ejection fraction. This study describes the impact of sacubitril/valsartan on HRQL in patients with HFpEF enrolled in the PARAGON-HF trial.<br /><b>Methods and results</b><br />Patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ) and EuroQol (EQ) at randomization, 4 months, 8 months, and annually thereafter. Changes in HRQL scores were evaluated using repeated measures models adjusted for treatment, baseline values and region. The pre-specified principal efficacy assessment was at 8 months at which time patients randomized to sacubitril/valsartan had borderline higher KCCQ-Clinical Summary score (CSS) with LSM adjusted difference of 1.0 (95% CI 0.0, 2.1); p=0.051. Including all visits up to 36 months, the LSM difference in KCCQ-CSS favored sacubitril/valsartan with average adjusted difference of 1.1 (95% CI 0.1, 2.0); p=0.034. Patients treated with sacubitril/valsartan had greater odds of clinically meaningful improvement (≥5-point increase) in KCCQ-CSS (OR 1.31; 95% CI 1.06, 1.61) at 8 months. At 8 months, there was no significant difference in the EQ visual analogue scale between the treatment arms, but sacubitril/valsartan was associated with higher EQ-5D utility score (US-based) with LSM adjusted difference of 0.01 (95% CI 0.00, 0.02); p=0.019.<br /><b>Conclusion</b><br />Compared with valsartan, sacubitril/valsartan has a borderline benefit on KCCQ-CSS at 8 months in patients with HFpEF. This benefit became more significant when data from all visits up to 36 months were included. This modest overall benefit was also supported by greater odds of patients reporting a clinically meaningful improvement in HRQL with sacubitril/valsartan. 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: 17 Nov 2022; epub ahead of print</small></div>
Chandra A, Polanczyk CA, Claggett BL, Vaduganathan M, ... Solomon SD, Lewis EF
Eur J Heart Fail: 17 Nov 2022; epub ahead of print | PMID: 36394533
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<div><h4>Inflammation across Universal Definition of Heart Failure Stages: The CASABLANCA Study.</h4><i>Mohebi R, Liu Y, van Kimmenade R, Gaggin HK, Murphy SP, Januzzi JL</i><br /><b>Aim</b><br />We sought to investigate the association of inflammatory biomarkers with incident heart failure (HF) events in patients at different stages of HF.<br /><b>Methods</b><br />1231 study participants undergoing diagnostic coronary and/or peripheral angiography were categorized by Universal definition of Heart Failure (UDHF) Stage A (at risk), Stage B (pre-HF), and Stages C or D (HF, including end-stage). Twenty-four inflammatory biomarkers were collected prior to angiography and unsupervised machine learning categorized levels of inflammation into three groups (low, medium, and high). Cox proportional hazard regression was implemented to assess the associations of inflammation level with incident HF hospitalization in each UDHF stage.<br /><b>Results</b><br />Using machine learning, study participants were grouped into low (N=443), medium (N=570) and high inflammation categories (N=230). Significantly higher concentrations of natriuretic peptide, troponin, and soluble ST2 were observed among those with high inflammation levels (p-value <.001). During 3.7 years of follow-up, 123 (15.1%) HF hospitalizations occurred in Stage A/B and 180 (41.8%) HF hospitalizations occurred in Stage C/D. In multivariable model considering low inflammation level as a reference, among patients with stage A/B, the HR (95% confidence interval [CI]) of incident HF was 2.31 (1.40-3.80) for moderate inflammation level, and 4.16 (2.35-7.37) for high inflammation level. Among patients with stage C/D, the corresponding HR (95% CI) of HF hospitalization was 1.98 (1.28-3.04) for moderate inflammation level, and 2.69 (1.69-4.28) for high inflammation level.<br /><b>Conclusion</b><br />Patterns of inflammation severity may have differing prognostic meaning across UDHF Stages. 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: 17 Nov 2022; epub ahead of print</small></div>
Mohebi R, Liu Y, van Kimmenade R, Gaggin HK, Murphy SP, Januzzi JL
Eur J Heart Fail: 17 Nov 2022; epub ahead of print | PMID: 36394549
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<div><h4>Effects of Empagliflozin on Erythropoiesis in Heart Failure: Data from the Empire HF Trial.</h4><i>Fuchs Andersen C, Omar M, Glenthøj A, El Fassi D, ... Schou M, Jensen J</i><br /><b>Aims</b><br />It remains unknown whether the consistently observed increase in haematocrit with sodium-glucose co-transporter-2 inhibitors (SGLT2i) is caused by diuresis-associated haemoconcentration or increased erythropoiesis. We aimed to investigate the early effect of empagliflozin on erythropoiesis and iron metabolism in patients with heart failure with reduced ejection fraction (HFrEF).<br /><b>Methods and results</b><br />The Empire HF was a double-blind, randomised, placebo-controlled trial. Patients with a left ventricular ejection fraction (LVEF) ≤40%, New York Heart Association (NYHA) Class I-III symptoms, and on stable guideline-directed HFrEF therapy were randomly assigned (1:1) to empagliflozin or matching placebo once daily for 12 weeks. Exploratory outcomes reflecting changes in erythropoiesis and iron metabolism were analysed. In total, 190 patients were randomised. Baseline characteristics were well-balanced between the groups [age: mean 64 (SD 11) years; male: 85%; LVEF: mean 29 (SD 8) %; NYHA Class II: 78%; T2D: 13%; anaemia: 28%; chronic kidney disease (CKD); 13%]. In this post hoc analysis, erythropoietin was increased with empagliflozin compared to placebo from baseline to 12 weeks [adjusted mean difference 2.6 IU/L (95% CI 0.8-4.4; P=0.0046)]. Moreover, hepcidin was reduced [adjusted ratio of change 0.76 (95% CI 0.59-0.97; P=0.031)], with no change observed for erythroferrone [adjusted ratio of change 1.17 (95% CI 0.86-1.60; P=0.31)] compared to placebo. No significant treatment-by-subgroup interactions were observed regarding baseline T2D, anaemia, or CKD (P<sub>interactions</sub> >0.05).<br /><b>Conclusion</b><br />These findings suggest that empagliflozin increases erythropoiesis and augments early iron utilization in patients with HFrEF. These mechanisms may contribute to the cardioprotective properties of empagliflozin. 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: 14 Nov 2022; epub ahead of print</small></div>
Fuchs Andersen C, Omar M, Glenthøj A, El Fassi D, ... Schou M, Jensen J
Eur J Heart Fail: 14 Nov 2022; epub ahead of print | PMID: 36377106
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<div><h4>How Can SGLT2 Inhibitors Stimulate Erythrocytosis in Patients Who Are Iron Deficient? Implications for Understanding Iron Hemostasis in Heart Failure.</h4><i>Packer M</i><br /><AbstractText>Many patients with heart failure have an iron-deficient state, which can limit erythropoiesis in erythroid precursors and ATP production in cardiomyocytes. Yet, treatment with sodium-glucose cotransporter 2 (SGLT2) inhibitors produce consistent increases in hemoglobin and hematocrit, even in patients who are iron-deficient before treatment, and this effect remains unattenuated throughout treatment even though SGLT2 inhibitors further aggravate biomarkers of iron deficiency. Heart failure is often accompanied by systemic inflammation, which activates hepcidin, thus impairing the duodenal absorption of iron and the release of iron from macrophages and hepatocytes, leading to a decline in circulating iron. Inflammation and oxidative stress also promote the synthesis of ferritin and suppress ferritinophagy, thus impairing the release of intracellular iron stores and leading to the depletion of bioreactive cytosolic Fe<sup>2+</sup> . By alleviating inflammation and oxidative stress, SGLT2 inhibitors down-regulate hepcidin, upregulate transferrin receptor protein 1 and reduce ferritin; the net result is to increase the levels of cytosolic Fe<sup>2+</sup> available to mitochondria, thus enabling the synthesis of heme (in erythroid precursors) and ATP (in cardiomyocytes). The finding that SGLT2 inhibitors can induce erythro-cytosis without iron supplementation suggests that the abnormalities in iron diagnostic tests in patients with mild-to-moderate heart failure are likely to be functional, rather than absolute, i.e., they are related to inflammation-mediated trapping of iron by hepcidin and ferritin, which is reversed by treatment with SGLT2 inhibitors. An increase in bioreactive cytosolic Fe<sup>2+</sup> is also likely to augment mitochondrial production of ATP in cardiomyocytes, thus retarding the progression of heart failure. These effects on iron metabolism are consistent with (1) proteomics analyses of placebo-controlled trials, which have shown that biomarkers of iron homeostasis represent the most consistent effect of SGLT2 inhibitors; and (2) statistical mediation analyses, which have reported striking parallelism of the effect of SGLT2 inhibitors to promote erythrocytosis and reduce heart failure events. 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: 14 Nov 2022; epub ahead of print</small></div>
Abstract
<div><h4>Dapagliflozin in patients with heart failure with mildly reduced and preserved ejection fraction treated with a mineralocorticoid receptor antagonist or sacubitril/valsartan.</h4><i>Yang M, Butt JH, Kondo T, Jering KS, ... Solomon SD, McMurray JJV</i><br /><b>Aims</b><br />The effects of adding a sodium-glucose cotransporter 2 (SGLT2) inhibitor to a mineralocorticoid receptor antagonist (MRA) or an angiotensin receptor-neprilysin inhibitor (ARNI) in patients with heart failure (HF) and mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) are uncertain, even though the use of all three drugs is recommended in recent guidelines.<br /><b>Methods and results</b><br />The efficacy and safety of dapagliflozin added to background MRA or ARNI therapy was examined in patients with HFmrEF/HFpEF enrolled in the DELIVER trial. The primary outcome was the composite of worsening HF or cardiovascular death. Of 6263 patients, 2667 (42.6%) were treated with an MRA and 301 (4.8%) with an ARNI at baseline. Patients taking either were younger, more often men and had lower systolic blood pressure and ejection fraction; they were also more likely to have prior HF hospitalization. The benefit of dapagliflozin was similar whether patients were receiving these therapies. The hazard ratio for the effect of dapagliflozin compared to placebo on the primary outcome was 0.86 (95% confidence interval [CI] 0.74-1.01) for MRA non-users versus 0.76 (95% CI 0.64-0.91) for MRA users (p<sub>interaction</sub>  = 0.30). The corresponding values for ARNI non-users and users were 0.82 (95% CI 0.73-0.92) and 0.74 (95% CI 0.45-1.22), respectively (p<sub>interaction</sub>  = 0.75). None of the adverse events examined was more common with dapagliflozin compared to placebo overall or in the MRA and ARNI subgroups.<br /><b>Conclusions</b><br />The efficacy and safety of dapagliflozin were similar, regardless of background treatment with an MRA or ARNI. SGLT2 inhibitors may be added to other treatments recommended in recent guidelines for HFmrEF/HFpEF.<br /><br />© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.<br /><br /><small>Eur J Heart Fail: 07 Nov 2022; epub ahead of print</small></div>
Yang M, Butt JH, Kondo T, Jering KS, ... Solomon SD, McMurray JJV
Eur J Heart Fail: 07 Nov 2022; epub ahead of print | PMID: 36342375
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<div><h4>Intersection of Atrial Fibrillation and Heart Failure with Mildly Reduced and Preserved Ejection Fraction in >400,000 Participants in the Get With The Guidelines Heart Failure Registry.</h4><i>Patel RB, Greene SJ, Xu H, Alhanti B, ... Fonarow GC, Vaduganathan M</i><br /><b>Aims</b><br />Although atrial fibrillation (AF) frequently coexists with heart failure with preserved ejection fraction (HFpEF), few data are available evaluating AF-specific care patterns and post-discharge outcomes in patients hospitalized for HFpEF. We evaluated AF-specific medical therapies and post-discharge outcomes among patients hospitalized for heart failure with mildly reduced ejection fraction (HFmrEF) or HFpEF by AF history.<br /><b>Methods and results</b><br />Trends in AF prevalence were evaluated among patients hospitalized for HFmrEF or HFpEF in the Get with The Guidelines-Heart Failure registry from 2014 to 2020. Among those with linked Centers for Medicare & Medicaid Services post-discharge data, we assessed associations of AF with 12-month outcomes and determined trends in post-discharge prescriptions. Among 429,464 patients (age 76-years [IQR: 65-85], 57% women), 216,486 (50%) had a history of AF. Over time, the proportion of patients with AF increased slightly. Among the 79,895 patients with post-discharge data, AF was independently associated with higher risk of mortality and all-cause readmissions at 12 months, with stronger associations in HFpEF than in HFmrEF (mortality HR: 1.13 [95% CI: 1.09-1.16] vs. HR: 1.03 [95% CI: 0.97-1.10], P<sub>interaction</sub> =0.009). Anti-arrhythmic drug use after HF hospitalization was low (18%) and increased modestly over time. Amiodarone accounted for 71% of total anti-arrhythmic drug prescriptions. Overall use of anticoagulants after HF hospitalization has significantly increased from 52% in 2014 to 61% 2019, but remained modest.<br /><b>Conclusion</b><br />Prevalence of AF is rising among patients hospitalized with HFpEF. Those with comorbid AF face elevated post-discharge risks of death and rehospitalization. Current use of pharmacological rhythm control is low. 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: 07 Nov 2022; epub ahead of print</small></div>
Patel RB, Greene SJ, Xu H, Alhanti B, ... Fonarow GC, Vaduganathan M
Eur J Heart Fail: 07 Nov 2022; epub ahead of print | PMID: 36343200
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<div><h4>Association of post-vaccination adverse reactions after influenza vaccine with mortality and cardiopulmonary outcomes in patients with high-risk cardiovascular disease: the INVESTED trial.</h4><i>Peikert A, Claggett BL, Kim K, Udell JA, ... Solomon SD, Vardeny O</i><br /><b>Aims</b><br />Influenza vaccination is associated with reduced cardiopulmonary morbidity and mortality among patients with heart failure or recent myocardial infarction. The immune response to vaccination frequently results in mild adverse reactions (AR), which leads to vaccine hesitancy. This post hoc analysis explored the association between vaccine-related AR and morbidity and mortality in patients with high-risk cardiovascular disease.<br /><b>Methods and results</b><br />The INVESTED trial randomized 5260 patients with recent heart failure hospitalization or acute myocardial infarction to high-dose trivalent or standard-dose quadrivalent inactivated influenza vaccine. We examined the association between vaccine-related AR and adverse clinical outcomes across both treatment groups in propensity-adjusted models. Among 5210 participants with available information on post-vaccination symptoms, 1968 participants (37.8%) experienced a vaccine-related AR. Compared to those without AR, post-vaccination AR, most commonly injection site pain (60.3%), were associated with lower risk for the composite of all-cause death or cardiopulmonary hospitalization (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.75-0.92, p < 0.001), cardiopulmonary hospitalizations (HR 0.85 [95% CI 0.76-0.95], p = 0.003), all-cause death (HR 0.77 [95% CI 0.62-0.96], p = 0.02), cardiovascular hospitalizations (HR 0.88 [95% CI 0.78-0.99], p = 0.03) and non-cardiopulmonary hospitalizations (HR 0.80 [95% CI 0.69-0.92], p = 0.003). While mild (76.4%) and moderate (20.6%) AR were most common and together associated with lower risk for the primary outcome (HR 0.81 [95% CI 0.74-0.90], p < 0.001), severe AR (2.9%) were related to increased risk (HR 1.68 [95% CI 1.17-2.42], p = 0.005).<br /><b>Conclusion</b><br />Mild to moderate post-vaccination reactions after influenza vaccine were associated with reduced risk of cardiopulmonary hospitalizations and all-cause mortality in patients with high-risk cardiovascular disease, while severe reactions may indicate increased risk. Mild to moderate AR to influenza vaccination may be a marker of immune response and should not deter future vaccinations.<br /><br />© 2022 European Society of Cardiology.<br /><br /><small>Eur J Heart Fail: 06 Nov 2022; epub ahead of print</small></div>
Peikert A, Claggett BL, Kim K, Udell JA, ... Solomon SD, Vardeny O
Eur J Heart Fail: 06 Nov 2022; epub ahead of print | PMID: 36335639
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<div><h4>Weight Change and Clinical Outcomes in Heart Failure with Reduced Ejection Fraction: Insights from EMPEROR-Reduced.</h4><i>Anker SD, Khan MS, Butler J, Ofstad AP, ... Pocock S, Packer M</i><br /><b>Aims</b><br />Baseline body mass index (BMI) and weight loss promoted by sodium-glucose co-transporter 2 inhibitors may impact outcomes in patients with heart failure with reduced ejection fraction (HFrEF). We assessed in the EMPEROR-Reduced population treated with empagliflozin vs placebo the relationship between baseline BMI, weight loss and effects on the primary (time to first hospitalization for heart failure [HHF] or cardiovascular death) and key secondary outcomes.<br /><b>Methods and results</b><br />We categorized patients according to their baseline BMI: <20 kg/m<sup>2</sup> , (n = 180); 20-<25 kg/m<sup>2</sup> (n = 1038); 25-<30 kg/m<sup>2</sup> (n = 1345); 30-<35 kg/m<sup>2</sup> (n = 774) and ≥35 kg/m<sup>2</sup> (n = 393). The treatment effect of empagliflozin on the primary outcome was consistent across all BMI categories (HRs in subgroups 0.66 to 0.88, interaction trend p = 0.32), as was the effect on total (first plus recurrent) HHF (interaction trend p = 0.31). Empagliflozin reduced the rate of eGFR decline consistently across the BMI categories (interaction trend p = 0.67). Overall, incidence rates of any or serious adverse events were comparable between the treatment groups across all BMI categories. Three-hundred-and thirteen (17.4%) of patients treated with empagliflozin experienced a weight loss of more than 5% at week 52 vs. 230 (12.8%) in placebo. When analyzed separately within each treatment group, presence of weight loss was similarly associated with an increased risk of all-cause mortality.<br /><b>Conclusion</b><br />The benefits of empagliflozin versus placebo were consistently present across all BMI categories in HFrEF patients. Weight loss was associated with higher risk of all-cause mortality, regardless of treatment group.<br /><br />This article is protected by copyright. All rights reserved.<br /><br /><small>Eur J Heart Fail: 02 Nov 2022; epub ahead of print</small></div>
Anker SD, Khan MS, Butler J, Ofstad AP, ... Pocock S, Packer M
Eur J Heart Fail: 02 Nov 2022; epub ahead of print | PMID: 36325584
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<div><h4>Evolution of tricuspid regurgitation after transcatheter edge-to-edge mitral valve repair for secondary mitral regurgitation and its impact on mortality.</h4><i>Adamo M, Pagnesi M, Ghizzoni G, Estévez-Loureiro R, ... Voors A, Metra M</i><br /><b>Aim</b><br />To evaluate short-term changes in tricuspid regurgitation (TR) after transcatheter edge-to-edge mitral valve repair (M-TEER) in secondary mitral regurgitation (SMR), their predictors and impact on mortality.<br /><b>Methods and results</b><br />This is a retrospective analysis of SMR patients undergoing successful M-TEER (post-procedural mitral regurgitation ≤2+) at 13 European centres. Among 503 patients evaluated 79 (interquartile range [IQR] 40-152) days after M-TEER, 173 (35%) showed ≥1 degree of TR improvement, 97 (19%) had worsening of TR, and 233 (46%) remained unchanged. Smaller baseline left atrial diameter and residual mitral regurgitation 0/1+ were independent predictors of TR ≤2+ after M-TEER. There was a significant association between TR changes and New York Heart Association class and pulmonary artery systolic pressure decrease at echocardiographic re-assessment. At a median follow-up of 590 (IQR 209-1103) days from short-term echocardiographic re-assessment, all-cause mortality was lower in patients with improved compared to those with unchanged/worsened TR (29.6% vs. 42.3% at 3 years; log-rank p = 0.034). Baseline TR severity was not associated with mortality, whereas TR 0/1+ and 2+ at short-term follow-up was associated with lower all-cause mortality compared to TR 3/4+ (30.6% and 35.6% vs. 55.6% at 3 years; p < 0.001). A TR ≤2+ after M-TEER was independently associated with a 42% decreased risk of mortality (p = 0.011).<br /><b>Conclusion</b><br />More than one third of patients with SMR undergoing successful M-TEER experienced an improvement in TR. Pre-procedural TR was not associated with outcome, but a TR ≤2+ at short-term follow-up was independently associated with long-term mortality. Optimal M-TEER result and a small left atrium were associated with a higher likelihood of TR ≤2+ after M-TEER.<br /><br />© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.<br /><br /><small>Eur J Heart Fail: 01 Nov 2022; 24:2175-2184</small></div>
Adamo M, Pagnesi M, Ghizzoni G, Estévez-Loureiro R, ... Voors A, Metra M
Eur J Heart Fail: 01 Nov 2022; 24:2175-2184 | PMID: 36482160
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This program is still in alpha version.