Journal: Eur J Heart Fail

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Abstract

Health-related quality of life in acute heart failure: Association between patient-reported symptoms and markers of congestion.

Lee MMY, Campbell RT, Claggett BL, Lewis EF, ... McMurray JJV, Platz E
Aims
The aim of this study was to examine the association between patient-reported symptoms and the extent of pulmonary congestion in acute heart failure (AHF).
Methods and results
In this prospective, observational study, patient-reported symptoms were assessed at baseline using the Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) (range 0-100; 0 worst) in patients hospitalized for AHF. In a subset, patient-reported dyspnea at rest and on exertion was examined (range 0-10; 10 worst) at baseline. In addition, 4-zone lung ultrasound (LUS) was performed at baseline at the time of echocardiography. B-lines were quantified offline, blinded to clinical findings, in a core laboratory. Chest x-ray (CXR) and physical examination findings were collected from the medical records. Among 322 patients (mean age 72, 60% men, mean LVEF 39%) with AHF, the median KCCQ-TSS score was 33 [interquartile range 18-48]. Worse KCCQ-TSS was associated with worse NYHA class, dyspnea at rest and on exertion, and peripheral edema (p trend <0.001 for all). However, KCCQ-TSS was not associated with the extent of pulmonary congestion, as assessed by the number of B-lines on LUS, or findings on CXR or physical examination (p trend > 0.30 for all). Similarly, KCCQ-TSS was not significantly associated with echocardiographic markers of left ventricular filling pressure, pulmonary pressure or with NT-proBNP.
Conclusions
Among patients hospitalized for AHF, at baseline, KCCQ-TSS was not associated with pulmonary congestion assessed by LUS, CXR or physical examination. These findings suggest that the profound reduction in KCCQ-TSS in patients with AHF may not be solely explained by pulmonary congestion. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 25 Sep 2022; epub ahead of print
Lee MMY, Campbell RT, Claggett BL, Lewis EF, ... McMurray JJV, Platz E
Eur J Heart Fail: 25 Sep 2022; epub ahead of print | PMID: 36161429
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Abstract

Diagnostic Performance of MicroRNAs in the Detection of Heart Failure with Reduced or Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.

Parvan R, Hosseinpour M, Moradi Y, Devaux Y, Cataliotti A, J J da Silva G
Aim
Chronic Heart Failure (CHF) can be classified as HF with preserved Ejection Fraction (HFpEF) or with reduced Ejection Fraction (HFrEF). Currently, there is an unmet need for a minimally invasive diagnostic tool for different forms of CHF. We aimed to investigate the diagnostic potential of circulating miRNAs for the detection of different CHF forms via a systematic review and meta-analysis approach.
Methods and results
Comprehensive search on Medline, Web of Science, Scopus, and EMBASE identified 45 relevant studies which were used for qualitative assessment. Out of these, 29 studies were used for qualitative and quantitative assessment and allowed to identify a miRNA panel able to detect HFrEF and HFpEF with areas under the curve (AUC) of 0.86 and 0.79, respectively. A panel of eight miRNAs (hsa-miR-18b-3p, hsa-miR-21-5p, hsa-miR-22-3p, hsa-miR-92b-3p, hsa-miR-129-5p, hsa-miR-320a-5p, hsa-miR-423-5p, and hsa-miR-675-5p) detected HFrEF cases with a sensitivity of 0.85, specificity of 0.88 and AUC of 0.91. A panel of seven miRNAs (hsa-miR-19b-3p, hsa-miR-30c-5p, hsa-miR-206, hsa-miR-221-3p, hsa-miR-328-5p, hsa-miR-375-3p, and hsa-miR-424-5p) identified HFpEF cases with a sensitivity of 0.82 and a specificity of 0.61.
Conclusions
Although conventional biomarkers (NT-proBNP and BNP) presented a better performance in detecting CHF patients, the results presented here pointed towards specific miRNA panels with potential additive values to circulating natriuretic peptides in the diagnosis of different classes of CHF. Equally important, miRNAs alone showed a reasonable capacity for \"ruling out\" patients with HFrEF or HFpEF. Additional studies with large populations are required to confirm the diagnostic potential of miRNAs for sub-classes of CHF.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 25 Sep 2022; epub ahead of print
Parvan R, Hosseinpour M, Moradi Y, Devaux Y, Cataliotti A, J J da Silva G
Eur J Heart Fail: 25 Sep 2022; epub ahead of print | PMID: 36161443
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Abstract

Characteristics and clinical outcomes of patients with acute heart failure with a supranormal left ventricular ejection fraction.

van Essen BJ, Tromp J, Ter Maaten JM, Greenberg BH, ... Metra M, Voors AA
Background
Recent data suggest that guideline directed medical treatment of patients with heart failure with reduced ejection fraction (HFrEF) might improve clinical outcomes in patients with heart failure (HF) up to a left ventricular ejection fraction (LVEF) of 55-65%, whereas patients with higher LVEF do not seem to benefit. Recent data have shown that LVEF may have a U-shaped relation with outcome, with poorer outcome also in patients with supranormal values. This suggests that patients with supranormal LVEF may be a distinctive group of patients METHODS AND
Results:
RELAX AHF-2 was a multicenter, placebo-controlled trial on the effects of serelaxin on 180-day cardiovascular (CV) mortality and worsening HF at day 5 in patients with acute HF. Echocardiograms were performed at hospital admission in 6128 patients. 155 (2.5%) patients were classified as HFsnEF (LVEF>65%), 1440 (23.5%) as HFpEF (LVEF 50-65%), 1353 (22.1%) as HFmrEF (LVEF 41-49%) and 3180 (51.9%) as HFrEF (LVEF<40%). Patients with HFsnEF compared to HFpEF were more often women, had higher prevalence of non-ischemic HF, had lower levels of natriuretic peptides, were less likely to be treated with beta-blockers and had higher blood urea nitrogen plasma levels. All-cause mortality was not statistically different between groups, although patients with HFsnEF had the highest numerical rate. A declining trend was seen in the proportion of 180-day deaths due to CV causes from HFrEF (290/359, 80.8%) to HFsnEF (14/24, 58.0%). The reverse was observed with death from non-cardiovascular causes. No treatment effect of serelaxin was observed in any of the subgroups.
Conclusions
In this study, only 2.5% of patients were classified as HFsnEF. HFsnEF was primarily characterized by female sex, lower natriuretic peptides and a higher risk of non-CV death. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 16 Sep 2022; epub ahead of print
van Essen BJ, Tromp J, Ter Maaten JM, Greenberg BH, ... Metra M, Voors AA
Eur J Heart Fail: 16 Sep 2022; epub ahead of print | PMID: 36114655
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Abstract

A Prospective Study on Myocardial Injury after BNT162b2 mRNA COVID-19 Fourth Dose Vaccination in Healthy Persons.

Levi N, Moravsky G, Weitsman T, Amsalem I, ... Wiener-Well Y, Hasin T
Aims
To prospectively evaluate the incidence of myocardial injury after the administration of the fourth dose BNT162b2 mRNA vaccine (Pfizer-BioNTech) against COVID-19.
Methods and results
Health care workers who received the BNT162b2 vaccine during the fourth dose campaign had blood samples collected for high-sensitivity cardiac troponin (hs-cTn) during vaccine administration and 2-4 days afterward. Vaccine-related myocardial injury was defined as hs-cTn elevation above the 99th percentile upper reference limit and >50% increase from baseline measurement. Participants with evidence of myocardial injury underwent assessment for possible myocarditis. Of 324 participants, 192 (59.2%) were females and the mean age was 51.8 ± 15.0 years. Twenty-one (6.5%) participants had prior COVID-19 infection, the mean number of prior vaccine doses was 2.9 ± 0.4, and the median time from the last dose was 147 [142-157] days. Reported vaccine-related adverse reactions included local pain at injection site in 57 (17.59%), fatigue in 39 (12.04%), myalgia in 32 (9.88%), sore throat in 21 (6.48%), headache in 18 (5.5%), fever ≥38o C in 16 (4.94%), chest pain in 12 (3.7%), palpitations in 7 (2.16%), and shortness of breath in one (0.3%) participant. Vaccine-related myocardial injury was demonstrated in two (0.62%) participants, one had mild symptoms and one was asymptomatic; both had a normal electrocardiogram and echocardiography.
Conclusion
In a prospective investigation, an increase in serum troponin levels was documented among 0.62% of healthy healthcare workers receiving the fourth dose BNT162b2 vaccine. The two cases had mild or no symptoms and no clinical sequela. (ClinicalTrials.gov Identifier: NCT05308680). This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 13 Sep 2022; epub ahead of print
Levi N, Moravsky G, Weitsman T, Amsalem I, ... Wiener-Well Y, Hasin T
Eur J Heart Fail: 13 Sep 2022; epub ahead of print | PMID: 36097844
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Abstract

Heart failure outcomes according to heart rate and effects of empagliflozin in patients of the EMPEROR-Preserved Trial.

Böhm M, Butler J, Mahfoud F, Filippatos G, ... Anker SD, EMPEROR-Preserved Trial Committees and Investigators
Aims
Empagliflozin reduces cardiovascular death (CVD) or heart failure hospitalization (HHF) in patients with HF and preserved ejection fraction (HFpEF). Treatment effects and safety in relation to resting heart rate (RHR) have not been studied.
Methods and results
The interplay of RHR and empagliflozin effects in EMPEROR-Preserved was evaluated. We grouped patients (n=5988) according to their baseline RHR [<70 bpm (n=2650), 70-75 bpm (n=967), >75 bpm (n=1736)] and explored the influence of RHR on CVD or HHF (primary outcome) and its components in sinus rhythm or atrial fibrillation/flutter (AF) and adverse events. We studied the efficacy of empagliflozin across the RHR spectrum. Compared to placebo, empagliflozin did not change heart rate over time. The primary outcome (p trend = 0.0004) and its components CVD (p trend = 0.0002), first HHF (p trend = 0.0099) and all-cause death (p=0.0001) increased with RHR only in sinus rhythm but not AF. The risk increase with RHR was similar in patients with HFmrEF (LVEF 40-49%) and HFpEF (LVEF >=50%). Baseline RHR had no influence on the effect of empagliflozin on the primary outcomes (p trend = 0.20), first HHF (p trend = 0.49). There were no clinically relevant differences in adverse events between empagliflozin and placebo across the RHR groups.
Conclusion
RHR associates with outcomes only in sinus rhythm but not in AF. Empagliflozin reduced outcomes over the entire RHR spectrum without increase of adverse events. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 10 Sep 2022; epub ahead of print
Böhm M, Butler J, Mahfoud F, Filippatos G, ... Anker SD, EMPEROR-Preserved Trial Committees and Investigators
Eur J Heart Fail: 10 Sep 2022; epub ahead of print | PMID: 36087309
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Abstract

A review from the Biomarkers Working Group of the Heart Failure Association of the ESC: A review from the Biomarkers Working Group of the Heart Failure Association of the ESC.

Bayes-Genis A, Aimo A, Jhund P, Richards AM, ... Emdin M, Januzzi JL
The approval of new heart failure (HF) therapies has slowed over the past two decades in part due to the high costs of conducting large randomized clinical trials that are needed to adequately power major clinical endpoint studies. Several biomarkers have been identified reflecting different elements of HF pathophysiology, with possible applications in diagnosis, risk stratification, treatment monitoring, and even in the design of clinical trials. Biomarkers could potentially be used to refine study inclusion criteria to enable enrolment of patients who are more likely to respond to a therapeutic intervention, despite being at sufficient risk to meet predetermined study endpoint rates. When there is a close relationship between biomarker levels and clinical endpoints, changes in biomarker levels after a given treatment can act as a surrogate endpoint, potentially reducing the duration and cost of a clinical trial. Natriuretic peptides have been widely used in clinical trials with a variable amount of added value, which such variation being probably due to the absence of a close pathophysiological connection to the study drug. Notable exceptions to this include sacubitril/valsartan and vericiguat. Future studies should seek to adopt unbiased approaches for discovery of true companion diagnostics; with -omics-based tools, biomarkers might be more precisely selected for use in clinical trials to identify responses that closely reflect the biological effects of the drug under investigation. Finally, biomarkers associated with cardiac damage and remodelling, such as cardiac troponin, could be employed as safety endpoints provided that standardization between different assays is achieved. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 08 Sep 2022; epub ahead of print
Bayes-Genis A, Aimo A, Jhund P, Richards AM, ... Emdin M, Januzzi JL
Eur J Heart Fail: 08 Sep 2022; epub ahead of print | PMID: 36073112
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Abstract

Dulaglutide and Cardiovascular and Heart Failure Outcomes in Patients With and Without Heart Failure: A Post-hoc Analysis from the REWIND Randomized Trial.

Branch KRH, Dagenais GR, Avezum A, Basile J, ... Chinthanie R, Probstfield JL
Aims
People with diabetes are at high risk for cardiovascular events including heart failure. We examined the effect of the glucagon-like peptide 1 agonist dulaglutide on incident heart failure events and other cardiovascular outcomes in those with or without prior heart failure the randomized placebo-controlled Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial (ClinicalTrials.gov number NCT01394952).
Methods and results
The REWIND major adverse cardiovascular event (MACE) outcome was the first occurrence of a composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes). In this post-hoc analysis, a heart failure event was defined as an adjudication-confirmed hospitalization or urgent evaluation for heart failure. Of the 9901 participants studied over a median follow-up of 5.4 years, 213/4949 (4.3%) randomly assigned to dulaglutide and 226/4952 (4.6%) participants assigned to placebo experienced a heart failure event (HR 0.93, 95% CI 0.77- 1.12; P=0.46). In the 853 (8.6%) participants with heart failure at baseline, there was no change in either MACE or heart failure events with dulaglutide as compared to participants without heart failure (p=0.44 and 0.19 for interaction, respectively). Combined CV death and heart failure events were marginally reduced with dulaglutide compared to placebo (HR 0.88, 95% CI: 0.78-1.00; p=0.050) but unchanged in patients with and without heart failure at baseline (p=0.31).
Conclusions
Dulaglutide was not associated with a reduction in HF events in patients with type 2 diabetes regardless of baseline HF status over 5.4 years of follow up. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 08 Sep 2022; epub ahead of print
Branch KRH, Dagenais GR, Avezum A, Basile J, ... Chinthanie R, Probstfield JL
Eur J Heart Fail: 08 Sep 2022; epub ahead of print | PMID: 36073143
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Abstract

Myocarditis Following COVID-19 Vaccine: Incidence, Presentation, Diagnosis, Pathophysiology, Therapy, and Outcomes put into Perspective.

Heidecker B, Dagan N, Balicer R, Eriksson U, ... Prasad S, Lüscher TF
Over 10 million doses of Covid-19 vaccines based on RNA technology, viral vectors, recombinant protein, and inactivated virus have been administered worldwide. Although generally very safe, post-vaccine myocarditis can result from adaptive humoral and cellular, cardiac-specific inflammation within days and weeks of vaccination. Rates of vaccine-associated myocarditis vary by age and sex with the highest rates in males between 12 and 39 years. The clinical course is generally mild with rare cases of left ventricular dysfunction, heart failure and arrhythmias. Mild cases are likely underdiagnosed as cardiac magnetic resonance imaging (CMR) is not commonly performed even in suspected cases and not at all in asymptomatic and mildly symptomatic patients. Hospitalization of symptomatic patients with ECG changes and increased plasma troponin levels is considered necessary in the acute phase to monitor for arrhythmias and potential decline in left ventricular function. In addition to evaluation for symptoms, ECG changes and elevated troponin levels, CMR is the best non-invasive diagnostic tool with endomyocardial biopsy (EMB) being restricted to severe cases with heart failure and/or arrhythmias. The management beyond guideline-directed management of heart failure and arrhythmias includes non-specific measures to control pain. Anti-inflammatory drugs such as non-steroidal anti-inflammatory drugs, and corticosteroids have been used in more severe cases, with only anecdotal evidence for their effectiveness. In all age groups studied, the overall risks of SARS-CoV-2 infection-related hospitalization and death are hugely greater than the risks from post-vaccine myocarditis. This consensus statement serves as a practical resource for physicians in their clinical practice, to understand, diagnose, and manage affected patients. Furthermore, it is intended to stimulate research in the area. This article is protected by copyright. All rights reserved.

© 2022 European Society of Cardiology.

Eur J Heart Fail: 06 Sep 2022; epub ahead of print
Heidecker B, Dagan N, Balicer R, Eriksson U, ... Prasad S, Lüscher TF
Eur J Heart Fail: 06 Sep 2022; epub ahead of print | PMID: 36065751
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Abstract

Renal effects of empagliflozin in patients hospitalized for acute heart failure: from the EMPULSE trial.

Voors AA, Damman K, Teerlink JR, Angermann CE, ... Ponikowski P, EMPULSE Trial Investigators
Introduction
The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin improved clinical outcomes in patients hospitalized for acute heart failure. In patients with chronic heart failure, SGLT2-inhibitors cause an early decline in estimated glomerular filtration rate (eGFR) followed by a slower eGFR decline over time than placebo. However, the effects of SGLT2-inhibitors on renal function during a hospital admission for acute heart failure remains largely unknown.
Methods and results
Between 1 to 5 days after a hospitalization for acute heart failure, 530 patients with an eGFR>20 mL/min/1.73m2 were randomized to 10 mg of empagliflozin or placebo and treated for 90 days. Renal function and electrolytes were measured at baseline, and after 15, 30 and 90 days. We evaluated the effect of empagliflozin on eGFR over time and the impact of baseline eGFR on the primary hierarchical outcome of death, worsening heart failure events and quality of life. Mean baseline eGFR was 52.4 mL/min/1.73m2 in the empagliflozin group and 55.7 mL/min/1.73m2 in the placebo group. Empagliflozin caused an initial decline in eGFR (-2 mL/min/1.73m2 at day 15 compared to placebo). At day 90, eGFR was similar between empagliflozin and placebo. Investigator reported acute renal failure occurred in 7.7% of empagliflozin versus 12.1% of placebo patients. The overall clinical benefit (hierarchical composite of all-cause death, heart failure events and quality of life) of empagliflozin was unaffected by baseline eGFR.
Conclusion
In patients hospitalized for acute heart failure, empagliflozin caused an early modest decline in renal function which was no longer evident after 90 days. Acute renal events were similar in both groups. The clinical benefit of empagliflozin was consistent regardless of baseline renal function. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 06 Sep 2022; epub ahead of print
Voors AA, Damman K, Teerlink JR, Angermann CE, ... Ponikowski P, EMPULSE Trial Investigators
Eur J Heart Fail: 06 Sep 2022; epub ahead of print | PMID: 36066557
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Abstract

Congestion in Heart Failure: a circulating biomarker-based perspective.

Núñez J, de la Espriella R, Rossignol P, Voors AA, ... Coats AJ, Bayes-Genis A
Congestion is a cardinal sign of heart failure (HF). In the past, it was seen as a homogeneous epiphenomenon that identified patients with advanced HF. However, current evidence shows that congestion in HF varies in quantity and distribution. This updated view advocates for a congestive-driven classification of HF according to onset (acute vs. chronic), regional distribution (systemic vs. pulmonary), compartment of distribution (intravascular vs. extravascular), and clinical vs. subclinical. Thus, this review will focus on the utility of circulating biomarkers for assessing and managing the different fluid overload phenotypes. This discussion focused on the clinical utility of the natriuretic peptides, carbohydrate antigen 125 (CA125, also called mucin 16 [MUC16]), bio-adrenomedullin and mid-regional pro-adrenomedullin, ST2 (also known as interleukin-1 receptor-like 1), cluster of differentiation 146 (CD146), troponin, C-terminal pro-endothelin-1, and parameters of hemoconcentration. The utility of circulation biomarkers on top of clinical evaluation, hemodynamics, and imaging-needs to be better determined by dedicated studies. Some multiparametric frameworks in which these tools contribute to management are proposed. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 30 Aug 2022; epub ahead of print
Núñez J, de la Espriella R, Rossignol P, Voors AA, ... Coats AJ, Bayes-Genis A
Eur J Heart Fail: 30 Aug 2022; epub ahead of print | PMID: 36039656
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Abstract

SACUBITRIL/VALSARTAN VERSUS RAMIPRIL FOR PATIENTS WITH ACUTE MYOCARDIAL INFARCTION: WIN-RATIO ANALYSIS OF THE PARADISE-MI TRIAL.

Berwanger O, Pfeffer M, Claggett B, Jering KS, ... Solomon SD, Braunwald E
Background
The win ratio can incorporate different types of outcomes and enhance statistical power, making it a useful method for analyzing composite outcomes in cardiovascular trials. The application of this approach to the PARADISE-MI trial provides an additional perspective into understanding the effects of sacubitril/valsartan in patients with acute myocardial infarction.
Methods
We conducted a post-hoc analysis of the PARADISE-MI trial, which randomly assigned patients with acute myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril/valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to guideline-recommended therapy. The principal composite outcome was analyzed in the hierarchical order of death due to cardiovascular causes, first hospitalization for heart failure, and first outpatient episode of symptomatic heart failure. We included events confirmed by the clinical event classification (CEC) committee as well as events identified by investigators that did not meet study definitions. Results were analyzed by the unmatched win ratio method. A win ratio that exceeds 1.00 reflects a better outcome.
Results
A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. The hierarchical analysis of the principal composite outcome demonstrated a larger number of wins [1,265,767 (15.7%)] than losses [1,079,502 (13.4%)] in the sacubitril/valsartan group (win ratio of 1.17, 95% confidence interval [CI],1.03 to 1.33; P=0.015). Sensitivity analyses using alternative definitions of the composite outcome showed results similar to those of the principal analysis, except for analysis restricted to events that met CEC definitions (win ratio of 1.11, 95% CI, 0.96 to 1.30; P=0.16).
Conclusion
In this post-hoc analysis of the PARADISE-MI trial using the win ratio and including investigator-identified events not having CEC confirmation, sacubitril/valsartan was superior to ramipril among high-risk survivors of acute myocardial infarction. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 29 Aug 2022; epub ahead of print
Berwanger O, Pfeffer M, Claggett B, Jering KS, ... Solomon SD, Braunwald E
Eur J Heart Fail: 29 Aug 2022; epub ahead of print | PMID: 36054480
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Abstract

Device-based remote monitoring strategies for congestion-guided management of patients with heart failure: a systematic review and meta-analysis.

Zito A, Princi G, Romiti GF, Galli M, ... Crea F, D\'Amario D
Aims
Preclinical congestion markers of worsening heart failure (HF) can be monitored by devices and may support the management of patients with HF. We aimed to assess whether congestion-guided HF management according to device-based remote monitoring strategies is more effective than standard therapy.
Methods and results
A comprehensive literature research for randomized controlled trials (RCTs) comparing device-based remote monitoring strategies for congestion-guided HF management versus standard therapy was performed on PubMed, Embase, and CENTRAL databases. Incidence rate ratios (IRRs) and associated 95% confidence intervals (CIs) were calculated using the Poisson regression model with random study effects. The primary outcome was a composite of all-cause death and HF hospitalizations. Secondary endpoints included the individual components of the primary outcome. A total of 4347 patients from 8 RCTs were included. Findings varied according to the type of parameters monitored. Compared with standard therapy, haemodynamic-guided strategy (4 trials, 2224 patients, 12-month follow-up) reduced the risk of the primary composite outcome (IRR 0.79, 95% CI 0.70-0.89) and HF hospitalizations (IRR 0.76, 95% CI 0.67-0.86), without a significant impact on all-cause death (IRR 0.93, 95% CI 0.72-1.21). In contrast, impedance-guided strategy (4 trials, 2123 patients, 19-month follow-up) did not provide significant benefits.
Conclusion
Haemodynamic-guided HF management is associated with better clinical outcomes as compared to standard clinical care.

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Eur J Heart Fail: 23 Aug 2022; epub ahead of print
Zito A, Princi G, Romiti GF, Galli M, ... Crea F, D'Amario D
Eur J Heart Fail: 23 Aug 2022; epub ahead of print | PMID: 36054801
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Abstract

Right Ventricular Dysfunction Predicts Outcome After Transcatheter Mitral Valve Repair For Primary Mitral Valve Regurgitation.

Doldi PM, Stolz L, Kalbacher D, Köll B, ... Massberg S, Hausleiter J
Aims
Right ventricular dysfunction (RVD) as expressed by right ventricular to pulmonary artery coupling has recently been identified as a strong outcome predictor in patients undergoing mitral valve edge-to-edge repair (M-TEER) for secondary mitral regurgitation. The aim of this study was to define RVD in patients undergoing M-TEER for primary MR (PMR) and to evaluate its impact on procedural MR reduction, symptomatic development and 2-year all-cause mortality.
Methods and results
This multicenter study included patients undergoing M-TEER for symptomatic PMR at 9 international centres. The study cohort was divided into a derivation (DC) and validation cohort (VC) for calculation and validation of the best discriminatory value for RVD. 648 PMR patients were included in the study. DC and VC were comparable regarding procedural success and outcomes at follow-up. Sensitivity analysis identified RVD as an independent predictor for 2-year mortality in the DC (HR: 2.37, 95%CI: 1.47-3.81, p<0.001), which was confirmed in the VC (HR: 2.06, 95%CI: 1.36-3.13, p<0.001). Procedural success (MR ≤2+) and symptomatic at follow-up (NYHA≤II) were lower in PMR patients with RVD (MR≤2+: 82% vs. 93% p=0.002; NYHA≤II: 57,3% vs. 66.5% p=0.09 for with vs. without RVD). In all PMR patients, the presence of RVD significantly impaired 2-year survival after M-TEER (HR: 2.23, 95%CI: 1.63-3.05, p<0.001).
Conclusions
M-TEER is an effective treatment option for PMR patients. The presence of RVD is associated with less MR reduction, less symptomatic improvement and increased 2-year mortality. Accordingly, RVD might be included into preprocedural prognostic considerations. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 23 Aug 2022; epub ahead of print
Doldi PM, Stolz L, Kalbacher D, Köll B, ... Massberg S, Hausleiter J
Eur J Heart Fail: 23 Aug 2022; epub ahead of print | PMID: 36054557
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Abstract

Albiglutide in patients with type 2 diabetes and heart failure: a post-hoc analysis from Harmony Outcomes.

Ferreira JP, Sharma A, Vasques-Nóvoa F, Angélico-Gonçalves A, ... Leite-Moreira A, Neves JS
Background
Glucagon-like peptide-1 receptor agonists (GLP1-RA) improve cardiovascular outcomes in patients with type 2 diabetes (T2D). However, some studies suggest that their effects in patients with heart failure (HF) may be attenuated. We aim to explore the effects of the GLP1-RA albiglutide on HF outcomes in patients with and without HF history enrolled in the Harmony Outcomes trial.
Methods
Harmony Outcomes enrolled patients with T2D and cardiovascular disease randomized to either albiglutide or placebo over a median follow-up of 1.6 years.
Results
9462 patients were included, of whom 1922 (20%) had HF history. Patients with HF had more cardiovascular comorbidities,poorer renal function, and had a 3 to 4-fold higher risk of HF events compared to patients without HF. Compared to placebo, the effect of albiglutide on the composite of cardiovascular death or HF hospitalization was more pronounced among patients without HF (HR=0.73, 95%CI=0.56-0.95) than in patients with HF (HR=1.06, 95%CI=0.79-1.43), interaction P=0.062. A similar pattern was observed for HF hospitalizations (interaction P=0.025). The effect of albiglutide on cardiovascular death, sudden death or \"pump failure\" death, and all-cause mortality was also attenuated among patients with HF history, but without significant interaction (P>0.1). The benefit of albiglutide to reduce atherosclerotic events was consistent regardless of HF history.
Conclusions
In patients with T2D and cardiovascular disease, albiglutide appeared to have no effect in reducing HF-related events among patients with HF history. These findings, placed in the context of other trials, suggest that GLP1-RA may not improve HF outcomes in patients with HF. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 23 Aug 2022; epub ahead of print
Ferreira JP, Sharma A, Vasques-Nóvoa F, Angélico-Gonçalves A, ... Leite-Moreira A, Neves JS
Eur J Heart Fail: 23 Aug 2022; epub ahead of print | PMID: 36053803
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Impact:
Abstract

Effects of remote haemodynamic-guided heart failure management in patients with different subtypes of pulmonary hypertension: Insights from the MEMS-HF study.

Assmus B, Angermann CE, Alkhlout B, Asselbergs FW, ... Böhm M, Rosenkranz S
Introduction
The CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) investigated safety and efficacy of pulmonary-artery-pressure (PAP)-guided remote patient management (RPM) in New York Heart Association (NYHA) Class III outpatients with at least one hospitalization for heart failure (HFH) during the previous 12 months. This pre-specified subgroup analysis investigated whether RPM effects depended on presence and subtype of pulmonary hypertension (PH).
Methods and results
In 106/234 MEMS-HF participants, Swan-Ganz catheter tracings obtained during sensor implant were available for off-line manual analysis jointly performed by two experts. Patients were classified into subgroups according to current PH definitions. Isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH) were present in 38 and 36 patients, respectively, whereas 31 patients had no PH. Clinical characteristics were comparable between subgroups, but among patients with PH pulmonary vascular resistance was higher (p=0.029) and pulmonary artery compliance lower (p=0.003) in patients with CpcPH. During 12 months of PAP-guided RPM, all PA pressures declined in IpcPH and CpcPH subgroups (all p<0.05), whereas only mean and diastolic PAP decreased in patients without PH (both p<0.05). Improvements in post- versus pre-implant HFH rates were similar in CpcPH (0.639 events/pt-yr; HR=0.37) and IpcPH (0.72 events/pt-yr; HR=0.45) patients. Participants without PH benefited most (0.26 events/pt-yr; HR=0.17, p=0.04 versus IpcPH/CpcPH patients). Quality-of-life and NYHA class improved significantly in all subgroups.
Conclusions
Outpatients with NYHA Class III symptoms with ≥ one HFH during one year pre-implant benefitted significantly from PAP-guided RPM during post-implant follow-up irrespective of presence or subtype of PH at baseline. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 23 Aug 2022; epub ahead of print
Assmus B, Angermann CE, Alkhlout B, Asselbergs FW, ... Böhm M, Rosenkranz S
Eur J Heart Fail: 23 Aug 2022; epub ahead of print | PMID: 36054647
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Abstract

Clinical characteristics and 1-year outcomes in hospitalized patients with heart failure with preserved ejection fraction: Results from the China Cardiovascular Association Database-Heart Failure Center Registry.

Cai A, Qiu W, Zhou Y, Feng Y, ... Dong Y, Yang J
Aim
We aimed to evaluate clinical characteristics and 1-year outcomes in hospitalized patients with heart failure with preserved ejection fraction (HFpEF) from China. Factors associated with outcomes (hospitalization for HF [HHF] and cardiovascular [CV] death) were assessed.
Method and results
Data were from the China Cardiovascular Association (CCA) Database-HF Center Registry. Between January 2017 and June 2021, 41708 hospitalized HFpEF patients with 1-year follow-up from 481 CCA Database-HF Center certified secondary and tertiary hospitals across overall 31 provinces of mainland China were included for this study. Of study participants (mean age 72.2 years and women 49.3%), 18.2% had HHF in prior 1-year and 55.8% had New York Heart Association class III/IV. Median left ventricular ejection fraction was 59%. Ischemia (26.6%), infection (14.4%) and arrhythmia (10.5%) were the three most common precipitating factors for index HF hospitalization. Nearly 67.4% had ≥ 3 comorbidities. Hypertension (65.2%), coronary heart disease (60.3%) and atrial fibrillation (41.2%) were the three most common comorbidities. Device and medication therapy which was noncompliance with current HF guideline recommendation was observed. The 1-year rate of clinical outcomes was 16.4%, with the 1-year rate of HHF was 13.6% and CV death was 3.1%, respectively. Factors associated with clinical outcomes included HHF in prior 1-year, serum level of sodium < 135 mmol/L and N-terminal pro-brain type natriuretic peptide > 1800 pg/mL.
Conclusion
HFpEF patients from China were characterized by high comorbid burden and high 1-year risk of HHF and CV death. Immediate efforts are needed to improve HFpEF management in China. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 23 Aug 2022; epub ahead of print
Cai A, Qiu W, Zhou Y, Feng Y, ... Dong Y, Yang J
Eur J Heart Fail: 23 Aug 2022; epub ahead of print | PMID: 36054149
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Abstract

Frequency of hereditary transthyretin amyloidosis among elderly patients with transthyretin cardiomyopathy.

Maestro-Benedicto A, Vela P, de Frutos F, Mora N, ... Lara-Pezzi E, Garcia-Pavia P
Aims
Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognized as a cause of heart failure in the elderly. Although wild-type ATTR-CM is the most frequent form of ATTR-CM found in the elderly, hereditary ATTR-CM (ATTRv) can also occur. We sought to determine the prevalence of ATTRv among elderly ATTR-CM patients, identify predictors of ATTRv and evaluate the clinical consequences of positive genetic testing in this population.
Methods and results
Prevalence of ATTRv in elderly ATTR-CM patients (≥70 years), was assessed in a cohort of 300 consecutive ATTR-CM patients (median age 78 years at diagnosis, 82% ≥70 years, 16% females, 99% Caucasian). ATTRv was diagnosed in 35 (12%; 95%CI: 3.1-8.8) and 13 (5.3%; 95%CI: 5.6-26.7) patients in the overall cohort and in those ≥70 years, respectively. Prevalence of ATTRv among elderly female patients with ATTR-CM was 13% (95%CI: 2.1-23.5). Univariate analysis identified female gender (OR: 3.66; 95%CI:1.13-11.85; p=0.03), black ancestry (OR 46.31; 95%CI:3.52-Inf; p=0.005), eye symptoms (OR: 6.64; 95%CI:1.20-36.73; p=0.03) and polyneuropathy (OR: 10.05; 95%CI:3.09-32.64; p<0.001) as the only factors associated with ATTRv in this population. Diagnosis of ATTRv in elderly ATTR-CM patients allowed initiation of TTR specific treatment in 5 individuals, genetic screening in 33 relatives from 13 families, and identification of 9 ATTRv asymptomatic carriers.
Conclusions
ATTRv is present in a substantial number of ATTR-CM patients ≥70 years. Identification of ATTRv in elderly patients with ATTR-CM has clinical meaningful therapeutic and diagnostic implications. These results support routine genetic testing in patients with ATTR-CM regardless of age. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 23 Aug 2022; epub ahead of print
Maestro-Benedicto A, Vela P, de Frutos F, Mora N, ... Lara-Pezzi E, Garcia-Pavia P
Eur J Heart Fail: 23 Aug 2022; epub ahead of print | PMID: 35999650
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Impact:
Abstract

Assessing Intrinsic Renal Sodium Avidity in Acute Heart Failure: Implications in Predicting and Guiding Decongestion.

Martens P, Chen HH, Verbrugge FH, Testani JT, Mullens W, Tang WHW
Background
Intrinsic renal sodium avidity (IRSA) is a hallmark feature of acute heart failure (AHF) and can be measured by evaluating the urinary sodium (Una) concentration.
Methods
A post-hoc analysis of the ROSE-AHF trial was performed in all patients with a random UNa spot sample before randomization (N=339/360). Patients were categorized according to tertiles of UNa as high (range=19-40mmol/l), intermediate (range=41-68mmol/l), or low (range=69-139mmol/l) IRSA. Linear mixed effect models and ANCOVA were used to assess the relation with decongestive effectiveness measured by: (a) weight change, (b) visual analog scale (VAS)-improvement, (c) NT-proBNP change, (d) natriuretic response (Una in mmol/L), (e) 72-hours natriuresis (mmol) (f) edema resolution, and (g) length of stay.
Results
High IRSA-patients had less improvement in decongestive metrics, including weight loss (p=0.028), VAS-improvement, NT-proBNP decrease, natriuretic-response (p-time interaction<0.001 for all), had lower total natriuresis (High IRSA=438±141 mmol, intermediate IRSA=526±320 mmol and low IRSA=603±276 mmol[p<0.001]), exhibited more edema at 72-hours(p=0.005), and had a longer length of stay(p=0.015). Incremental loop diuretic dose-titration (±4-times home dose) after >24 hours, resulted in an increase in natriuretic response in the high IRSA-group, however cumulative natriuresis still remained lower at 72hours(p<0.001). Longitudinal UNa-profiling of patients with low IRSA showed physiologic breaking in the UNa-pattern, associated with attaining decongestion and slight increase in creatinine and cystatin C, forming a potential signal of complete decongestion.
Conclusions
A simple random UNa-sample at the time of AHF, gives insight into IRSA which is consistently associated with decongestive effectiveness across multiple metrics, offering an opportunity for early AHF-care improvement. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 23 Aug 2022; epub ahead of print
Martens P, Chen HH, Verbrugge FH, Testani JT, Mullens W, Tang WHW
Eur J Heart Fail: 23 Aug 2022; epub ahead of print | PMID: 36054180
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Abstract

Dapagliflozin and New York Heart Association functional class in heart failure with mildly reduced or preserved ejection fraction: the DELIVER trial.

Ostrominski JW, Vaduganathan M, Claggett BL, de Boer RA, ... McMurray JJV, Solomon SD
Aims
This pre-specified analysis of the DELIVER trial examined whether clinical benefits of dapagliflozin in heart failure (HF) with left ventricular ejection fraction (LVEF) >40% varied by baseline New York Heart Association (NYHA) class and examined the treatment effects on NYHA class over time.
Methods and results
Treatment effects of dapagliflozin by baseline NYHA class II (n = 4713) versus III/IV (n = 1549) were examined on the primary endpoint (cardiovascular death or worsening HF event) and key secondary endpoints. Effects of dapagliflozin on change in NYHA class at 4, 16, and 32 weeks were also evaluated. Higher baseline NYHA class was associated with older age, female sex, greater comorbidity burden, lower LVEF, and higher natriuretic peptide levels. Participants with baseline NYHA class III/IV, as compared with II, were independently more likely to experience the primary endpoint (adjusted hazard ratio [HR] 1.16 [95% confidence interval, 1.02-1.33]) and all-cause death (adjusted HR 1.22 [1.06-1.40]). Dapagliflozin consistently reduced the risk of the primary endpoint compared with placebo, irrespective of baseline NYHA class (HR 0.81 [0.70-0.94] for NYHA class II vs. HR 0.80 [0.65-0.98] for NYHA class III/IV; pinteraction  = 0.921). Participants with NYHA class III/IV had greater improvement in Kansas City Cardiomyopathy Questionnaire total symptom scores between baseline and 32 weeks (+4.8 [2.5-7.1]) versus NYHA class II (+1.8 [0.7-2.9]; pinteraction  = 0.011). Dapagliflozin was associated with higher odds of any improvement in NYHA class (odds ratio [OR] 1.32 [1.16-1.51]), as well as improvement to NYHA class I (OR 1.43 [1.17-1.75]), versus placebo at 32 weeks, with benefits seen as early as 4 weeks.
Conclusions
Among symptomatic patients with HF and LVEF >40%, treatment with dapagliflozin provided clinical benefit irrespective of baseline NYHA class and was associated with early and sustained improvements in NYHA class over time.

© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Eur J Heart Fail: 11 Aug 2022; epub ahead of print
Ostrominski JW, Vaduganathan M, Claggett BL, de Boer RA, ... McMurray JJV, Solomon SD
Eur J Heart Fail: 11 Aug 2022; epub ahead of print | PMID: 36054231
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Abstract

Liver tests and outcomes in heart failure with reduced ejection fraction: findings from DAPA-HF.

Adamson C, Cowan LM, de Boer RA, Diez M, ... McMurray JJV, Jhund PS
Aims
Reflecting both increased venous pressure and reduced cardiac output, abnormal liver tests are common in patients with severe heart failure and are associated with adverse clinical outcomes. We aimed to investigate the prognostic significance of abnormal liver tests in ambulatory patients with heart failure with reduced ejection fraction (HFrEF), explore any treatment interaction between bilirubin and sodium-glucose cotransporter 2 (SGLT2) inhibitors and examine change in liver tests with SGLT2 inhibitor treatment.
Methods and results
We explored these objectives in the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, with focus on bilirubin. We calculated the incidence of cardiovascular death or worsening heart failure by bilirubin tertile. Secondary cardiovascular outcomes were examined, along with the change in liver tests at the end-of-study visit. Baseline bilirubin was available in 4720 patients (99.5%). Participants in the highest bilirubin tertile (T3) have more severe HFrEF (lower left ventricular ejection fraction, higher N-terminal pro-B-type natriuretic peptide [NT-proBNP] and worse New York Heart Association class), had a greater burden of atrial fibrillation but less diabetes. Higher bilirubin (T3 vs. T1) was associated with worse outcomes even after adjustment for other predictive variables, including NT-proBNP and troponin T (adjusted hazard ratio for the primary outcome 1.73 [95% confidence interval 1.37-2.17], p < 0.001; and 1.52 [1.12-2.07], p = 0.01 for cardiovascular death). Baseline bilirubin did not modify the benefits of dapagliflozin. During follow-up, dapagliflozin had no effect on liver tests.
Conclusion
Bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of dapagliflozin in HFrEF. Dapagliflozin was not associated with change in liver tests.
Clinical trial registration
ClinicalTrials.gov NCT03036124.

© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Eur J Heart Fail: 06 Aug 2022; epub ahead of print
Adamson C, Cowan LM, de Boer RA, Diez M, ... McMurray JJV, Jhund PS
Eur J Heart Fail: 06 Aug 2022; epub ahead of print | PMID: 36054568
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Impact:
Abstract

Bending oxygen saturation index and risk of worsening heart failure events in chronic heart failure.

de la Espriella R, Amiguet M, Miñana G, Rodríguez JC, ... Bayés-Genís A, Núñez J
Aims
Bendopnea is a clinical symptom of advanced heart failure with uncertain prognostic value. We aimed to evaluate whether bendopnea and the change in oxygen saturation when bending forward (bending oxygen saturation index [BOSI]) are associated with adverse outcomes in ambulatory chronic heart failure (CHF) patients.
Methods and results
We prospectively evaluated 440 subjects with symptomatic CHF. BOSI was defined as the difference between sitting and bending oxygen saturation (SpO2 ). The endpoint was the total number of worsening heart failure (WHF) events (heart failure hospitalization or urgent heart failure visit requiring parenteral diuretic therapy). The mean age was 74 ± 10 years, 257 (58.6%) were male, and 226 (51.4%) had a left ventricular ejection fraction <50%. Bendopnea was present in 94 (21.4%) patients, and 120 (27.3%) patients had a BOSI ≥-3%. The agreement between BOSI ≥-3% and bendopnea was moderate (Gwet\'s AC 0.482, p < 0.001). At a median (p25%-p75%) follow-up of 2.17 years (0.88-3.16), we registered 441 WHF events in 148 patients. After multivariable adjustment, BOSI was independently associated with the risk for total WHF episodes (overall, p < 0.001). Compared to improvement/no change in SpO2 when bending (BOSI 0%), those with BOSI ≥-3% showed an increased risk of WHF events (incidence rate ratio [IRR] 2.16, 95% confidence interval [CI] 1.67-2.79; p < 0.001). In contrast, bendopnea was not associated with the risk of total WHF episodes (IRR 1.04, 95% CI 0.83-1.31; p = 0.705).
Conclusions
In ambulatory and stable CHF patients, BOSI ≥-3% and not bendopnea was independently associated with an increased risk of total (first and recurrent) WHF episodes. Awareness of SpO2 while assessing bendopnea may be a useful tool for predicting heart failure decompensations.

© 2022 European Society of Cardiology.

Eur J Heart Fail: 06 Aug 2022; epub ahead of print
de la Espriella R, Amiguet M, Miñana G, Rodríguez JC, ... Bayés-Genís A, Núñez J
Eur J Heart Fail: 06 Aug 2022; epub ahead of print | PMID: 36054502
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Impact:
Abstract

Atrial amyloidosis: mechanisms and clinical manifestations.

Vergaro G, Aimo A, Rapezzi C, Castiglione V, ... Emdin M, Braunwald E
Cardiac amyloidosis (CA) is now recognized as an important cause of heart failure. Increased wall thickness and diastolic dysfunction of the left ventricle (LV) are the most easily detectable manifestations of CA, but amyloid accumulates in all cardiac structures. Involvement of the left and right atria may be due to the haemodynamic effects of ventricular diastolic dysfunction, the effects of amyloid infiltration into the atrial wall, and the cardiotoxic damage of atrial cardiomyocytes by amyloid precursors. Atrial amyloidosis is an early manifestation of CA, and is associated with an increased risk of atrial fibrillation (AF) and thromboembolic events. Furthermore, atrial amyloidosis can be found even in the absence of systemic disease and ventricular involvement. This condition is named isolated atrial amyloidosis and is due to a local overproduction of atrial natriuretic peptide. In this review we summarize the evidence on the mechanisms and clinical relevance of atrial amyloidosis. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 03 Aug 2022; epub ahead of print
Vergaro G, Aimo A, Rapezzi C, Castiglione V, ... Emdin M, Braunwald E
Eur J Heart Fail: 03 Aug 2022; epub ahead of print | PMID: 35920110
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Impact:
Abstract

Trajectories in New York Heart Association functional class in heart failure across the ejection fraction spectrum: data from the Swedish Heart Failure Registry.

Lindberg F, Lund LH, Benson L, Dahlström U, ... Rosano G, Savarese G
Aims
To investigate incidence, predictors and prognostic implications of longitudinal New York Heart Association (NYHA) class changes (i.e. improving or worsening vs. stable NYHA class) in heart failure (HF) across the ejection fraction (EF) spectrum.
Methods and results
From the Swedish HF Registry, 13 535 patients with EF and ≥2 NYHA class assessments were considered. Multivariable multinomial regressions were fitted to identify the independent predictors of NYHA change. Over a 1-year follow-up, 69% of patients had stable, 17% improved, and 14% worsened NYHA class. Follow-up in specialty care predicted improving NYHA class, whereas an in-hospital patient registration, lower EF, renal disease, lower mean arterial pressure, older age, and longer HF duration predicted worsening. The association between NYHA change and subsequent outcomes was assessed with multivariable Cox models. When adjusting for the NYHA class at baseline, improving NYHA class was independently associated with lower while worsening with higher risk of all-cause and cardiovascular mortality, and first HF hospitalization. After adjustment for the NYHA class at follow-up, NYHA class change did not predict morbidity/mortality. NYHA class assessment at baseline and follow-up predicted morbidity/mortality on top of the changes. Results were consistent across the EF spectrum.
Conclusion
In a large real-world HF population, NYHA class trajectories predicted morbidity/mortality after extensive adjustments. However, the prognostic role was entirely explained by the resulting NYHA class, i.e. the follow-up value. Our results highlight that considering one-time NYHA class assessment, rather than trajectories, might be the preferable approach in clinical practice and for clinical trial design.

© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Eur J Heart Fail: 02 Aug 2022; epub ahead of print
Lindberg F, Lund LH, Benson L, Dahlström U, ... Rosano G, Savarese G
Eur J Heart Fail: 02 Aug 2022; epub ahead of print | PMID: 35999668
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Abstract

Longitudinal Trajectories in Renal Function Before and After Heart Failure Hospitalization Among Patients with HFpEF in the PARAGON-HF Trial.

Chatur S, Vaduganathan M, Peikert A, Claggett BL, ... McMurray JJ, Solomon SD
Aims
Worsening renal function may impact long-term outcomes in heart failure (HF). However, little is known about the longitudinal trajectories in renal function in relation to the HF hospitalization or how this high-risk clinical event impacts renal outcomes.
Methods and results
In PARAGON-HF, we evaluated the association between recency of prior HF hospitalization (occurring pre-randomization) and subsequent first renal composite outcome: (1) time to ≥50% decline in eGFR ; (2) development of end stage renal disease (ESRD); or (3) death attributable to renal causes. 2,306 (48.1%) patients had a history of prior HF hospitalization. Incident rates of the renal outcome were highest in those most recently hospitalized and decreased with longer time from last hospitalization. Treatment effect on the renal outcome of sacubitril/valsartan vs. valsartan was similar between patients with (HR 0.43; 95% CI: 0.26 to 0.75) and without (HR 0.63; 95% CI: 0.33 to 1.18; Pinteraction = 0.39) a prior history of HF hospitalization and appeared consistent regardless of timing of prior hospitalization for HF (Pinteraction =0.39). Serial eGFR measurements leading up to and after a HF hospitalization (occurring during the study period) and estimated eGFR trajectories using repeated measures regression models with restricted cubic splines were also examined. Patients experiencing a post-randomization HF hospitalization had a significant decline in eGFR prior to hospitalization while patients without HF hospitalization experienced a relatively stable eGFR trajectory (p<0.001). A change in the rate of decline of eGFR trajectory was observed 12-months preceding a HF hospitalization, and continued in the post-discharge window to 12 months following hospitalization.
Conclusions
HF hospitalization denotes increased risk for kidney disease progression which continues following recovery from HF decompensation in patients with HF with preserved ejection fraction.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 27 Jul 2022; epub ahead of print
Chatur S, Vaduganathan M, Peikert A, Claggett BL, ... McMurray JJ, Solomon SD
Eur J Heart Fail: 27 Jul 2022; epub ahead of print | PMID: 35895867
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Impact:
Abstract

Intravenous iron therapy improves the hypercapnic ventilatory response and sleep disordered breathing in chronic heart failure.

Caravita S, Faini A, Vignati C, Pelucchi S, ... Agostoni P, Parati G
Background
Intravenous iron therapy can improve symptoms in patients with heart failure, anemia and iron deficiency. The mechanisms underlying such an improvement might involve chemoreflex sensing and nocturnal breathing patterns.
Methods
Patients with heart failure, reduced left ventricular ejection fraction, anemia (hemoglobin <13 g/dL in men; <12 g/dL in women) and iron deficiency (ferritin <100 or 100-299 mcg/L with transferrin saturation <20%) were 2:1 randomized to patients-tailored intravenous ferric carboxymaltose dose or placebo. Chemoreflex sensitivity cardiorespiratory sleep study, symptom assessment and cardiopulmonary exercise test were performed before and two weeks after the last treatment dose.
Results
Fifty-eight patients (38 active arm / 20 placebo arm) completed the study. Intravenous iron was associated with less severe symptoms, higher hemoglobin (12.5±1.4 vs. 11.7±1.0mg/dl p<0.05) and improved hematinic parameters. Ferric carboxymaltose improved the central hypercapnic ventilatory response (-25.8%, p<0.05 vs. placebo), without changes in peripheral chemosensitivity. In particular, the central hypercapnic ventilatory responses passed from 4.6±6.5 to 2.9±2.9 L/min/mmHg after ferric carboxymaltose and from 4.4±4.6 to 4.6±3.9 L/min/mmHg after placebo (ptreatment*condition =0.046). In patients presenting with sleep-related breathing disorder, apnea-hypopnea index was reduced with active treatment as compared to placebo (12±11 vs. 19±13 events/h, p<0.05). After ferric carboxymaltose, but not after placebo, both peak oxygen uptake (VO2) increased (Δ1.1±2.0 mL/Kg/min, p<0.05) and VO2/workload slope was steeper (Δ0.67±1.7 L/min/W, p<0.01).
Conclusions
Intravenous ferric carboxymaltose improves the hypercapnic ventilatory response and sleep-related breathing disorders in patients with heart failure, anemia and iron deficiency. These newly described findings, along with improved oxygen delivery to exercising muscles, likely contribute to the favorable effects of ferric carboxymaltose in anemic patients with heart failure. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 22 Jul 2022; epub ahead of print
Caravita S, Faini A, Vignati C, Pelucchi S, ... Agostoni P, Parati G
Eur J Heart Fail: 22 Jul 2022; epub ahead of print | PMID: 35867685
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Impact:
Abstract

Accelerating Cardiovascular Research: Recent Advances in Translational 2D and 3D Heart Models.

Mohr E, Thum T, Bär C
In vitro modelling the complex (patho-) physiological conditions of the heart is a major challenge in cardiovascular research. In recent years, methods based on three-dimensional (3D) cultivation approaches have steadily evolved to overcome the major limitations of conventional adherent monolayer cultivation (2D). These 3D approaches aim to study, reproduce or modify fundamental native features of the heart such as tissue organization and cardiovascular microenvironment. Therefore, these systems have great potential for (patient-specific) disease research, for the development of new drug screening platforms, and for the use in regenerative and replacement therapy applications. Consequently, continuous improvement and adaptation is required with respect to fundamental limitations such as cardiomyocyte maturation, scalability, heterogeneity, vascularization, and reproduction of native properties. In this review, 2D monolayer culturing and the 3D in vitro systems of cardiac spheroids, organoids, engineered cardiac microtissue and bioprinting as well as the ex vivo technique of myocardial slicing are introduced with their basic concepts, advantages, and limitations. Furthermore, recent advances of various new approaches aiming to extend as well as to optimize these in vitro and ex vivo systems are presented. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 22 Jul 2022; epub ahead of print
Mohr E, Thum T, Bär C
Eur J Heart Fail: 22 Jul 2022; epub ahead of print | PMID: 35867781
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Impact:
Abstract

Safety and Efficacy of Istaroxime for Patients with Acute-Heart-Failure-Related Pre-cardiogenic Shock - A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study (SEISMiC).

Metra M, Chioncel O, Cotter G, Davison B, ... Soffer J, Simonson S
Aims
We examined the effects of istaroxime in patients hospitalized for acute heart failure (AHF) related Society for Cardiovascular Angiography and Interventions (SCAI) stage B pre-cardiogenic shock (CS).
Methods and results
Sixty patients with AHF without acute myocardial infarction with pre-CS, defined as systolic blood pressure (SBP) < 90 mmHg without hypoperfusion, venous lactate > 2 mmol/L and/or mechanical or inotropic support, were randomised to istaroxime 1.0 -1.5 μg/kg/min or placebo for 24 hours. The primary endpoint, the adjusted area under the curve (AUC) change in SBP from time of treatment to 6 hours, was 53.1 (SE 6.88) mmHgxhour versus 30.9 (SE 6.76) mmHgxhour with istaroxime versus placebo (p=0.017). Adjusted SBP AUC at 24 hours was 291.2 (SE 27.5) versus 208.7 (SE 27.0) mmHgxhour (p=0.025). At 24 hours, some echocardiographic measurements improved with istaroxime versus placebo including cardiac index (+0.21 L/min/m2 ; p = 0.016), left atrial area (-1.8 cm2 ; p = 0.008), and left ventricular end systolic volume (-12.0 ml; p =0.034). There were no significant differences in pulse, laboratory measurements, serious adverse events or adverse events between the treatment groups except for more nausea, vomiting and infusion site pain in the istaroxime-treated patients. In a post-hoc analysis, patients receiving ≤1.0 μg/kg/min versus 1.5 μg/kg/min had similar increase in BP, but a trend towards less adverse events.
Conclusion
In phase 2a study of patients with AHF related pre-CS istaroxime improved BP and some echocardiography measures related to HF and was well tolerated. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 22 Jul 2022; epub ahead of print
Metra M, Chioncel O, Cotter G, Davison B, ... Soffer J, Simonson S
Eur J Heart Fail: 22 Jul 2022; epub ahead of print | PMID: 35867804
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Impact:
Abstract

Effects of Steroidal Mineralocorticoid Receptor Antagonists on Acute and Chronic Estimated Glomerular Filtration Rate Slopes in Patients with Chronic Heart Failure.

Vaduganathan M, Ferreira JP, Rossignol P, Neuen B, ... Zannad F, Solomon SD
Aims
Steroidal mineralocorticoid receptor antagonists (MRAs) form a cornerstone of the management of heart failure (HF), but little is known about the long-term effects of MRA therapy on kidney function. We evaluated acute and chronic estimated glomerular function (eGFR) slopes in the 2 largest completed trials testing steroidal MRAs in chronic HF.
Methods and results
We conducted parallel post hoc eGFR slope analyses in 2 multinational, double-blind randomized, placebo-controlled trials of steroidal MRAs in chronic HF with reduced ejection fraction (EMPHASIS-HF) and preserved ejection fraction (TOPCAT Americas region). GFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. Annual slopes of eGFR were assessed by generalized random coefficient models. Least square mean differences of eGFR slopes between steroidal MRA and placebo arms. Median follow-up was 1.8 years (EMPHASIS-HF) and 3.3 years (TOPCAT Americas). From baseline to month 4-6 (\"acute eGFR slope\"), compared to placebo, MRA treatment led to an acute decline in eGFR of -2.4 mL/min/1.73m2 (95% CI -3.4 to -1.4; P <0.001) and -2.0 mL/min/1.73m2 (95% CI -3.0 to -1.8; P <0.001) in EMPHASIS-HF and TOPCAT Americas, respectively. From month 4-6 to end of study, there was no difference in \"chronic eGFR slope\" between MRA and placebo arms (-0.3 mL/min/1.73m2 /year [95% CI -1.3 to 0.7; P =0.53] and 0.1 mL/min/1.73m2 /year [95% CI -1.4 to 1.7; P =0.86]) in EMPHASIS-HF and TOPCAT Americas, respectively.
Conclusions
Steroidal MRAs result in acute declines in eGFR but do not modify long-term kidney disease trajectories in chronic HF with reduced or preserved ejection fraction. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 22 Jul 2022; epub ahead of print
Vaduganathan M, Ferreira JP, Rossignol P, Neuen B, ... Zannad F, Solomon SD
Eur J Heart Fail: 22 Jul 2022; epub ahead of print | PMID: 35867859
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Impact:
Abstract

Value of the HFA-PEFF and H FPEF scores in patients with heart failure and preserved ejection fraction caused by cardiac amyloidosis.

Tomasoni D, Aimo A, Merlo M, Nardi M, ... Emdin M, Metra M
Aims
The HFA-PEFF and H2 FPEF scores have been developed to diagnose heart failure with preserved ejection fraction (HFpEF), and hold prognostic value. Their value in patients with HFpEF caused by cardiac amyloidosis (CA) has never been investigated.
Methods and results
We evaluated the diagnostic and prognostic value of the HFA-PEFF and H2 FPEF scores in 304 patients from 3 cohorts with HFpEF caused by transthyretin (ATTR)-CA (n=160, 53%) or immunoglobulin light-chain (AL)-CA (n=144, 47%). A diagnosis of HFpEF was more likely using the HFA-PEFF score with 2 (1%), 71 (23%), and 231 (76%) patients ranked as having a low (0-1), intermediate (2-4) or high (5-6) probability of HFpEF, respectively. Conversely, 36 (12%), 179 (59%) and 89 (29%) of patients ranked as having a low (0-1), intermediate (2-5) or high (6-9) probability of HFpEF using the H2 FPEF score. During a median follow-up of 19 months (interquartile range 8-40), 132 (43%) patients died. The HFA-PEFF score, but not the H2 FPEF, predicted a high risk of all-cause death which remained significant after adjustment for age, AL-CA diagnosis, high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, and echocardiographic parameters, including left ventricular (LV) global longitudinal strain, LV diastolic function and right ventricular function (hazard ratio 1.51, 95% confidence interval 1.16-1.95, p=0.002 for every 1-point increase in HFA-PEFF).
Conclusions
The HFA-PEFF score has a higher diagnostic utility in HFpEF caused by CA and holds independent prognostic value for all-cause mortality, while the H2 FPEF score does not. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 20 Jul 2022; epub ahead of print
Tomasoni D, Aimo A, Merlo M, Nardi M, ... Emdin M, Metra M
Eur J Heart Fail: 20 Jul 2022; epub ahead of print | PMID: 35855616
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Impact:
Abstract

Cardiac Contractility Modulation Therapy Improves Health Status in Patients with Heart Failure with Preserved Ejection Fraction; a Pilot Study (CCM-HFpEF).

Linde C, Grabowski M, Ponikowski P, Rao I, Stagg A, Tschöpe C
Aims
This pilot study aimed to assess the potential benefits of CCM in patients with HF with preserved left ventricular (LV) EF (HFpEF).
Methods and results
This was a prospective, multi-center, single-arm, pilot study of CCM therapy in patients with HFpEF and NYHA Class II or III. Echocardiogram parameters were measured by an echo core laboratory to determine study eligibility. After CCM device implantation, patients were followed for 24 weeks. Forty-seven patients, 70.2% women, 74.3+4.4 years old, with LVEF of 59+4.4%, 63.8% with hypertension, 46.8% with atrial fibrillation, 40.4% with diabetes, 31.9% with at least 1 HF hospitalization in the prior year, 61.7% NYHA Class III, and KCCQ overall score 48.9+21.7 were enrolled. The primary efficacy endpoint, mean change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall score, improved by 18.0 ± 16.6 points (p<0.001) and there was an event-free rate of 93.6% for the primary safety endpoint, device- and procedure-related complications, as adjudicated by an independent physician adjudication committee.
Conclusion
This pilot study demonstrates that the benefits of CCM may extend to the HFpEF patient population. The significant improvement in health status observed, with no obvious impact of safety, suggests that utilization of CCM for patients with HFpEF could prove to be promising. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 20 Jul 2022; epub ahead of print
Linde C, Grabowski M, Ponikowski P, Rao I, Stagg A, Tschöpe C
Eur J Heart Fail: 20 Jul 2022; epub ahead of print | PMID: 35855646
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Impact:
Abstract

Clinical Effect of Obesity on NT-proBNP Cut-off Concentrations for the Diagnosis of Acute Heart Failure.

Kozhuharov N, Martin J, Wussler D, Lopez-Ayala P, ... Mueller C, BASEL V investigators
Background
Obese patients have lower natriuretic peptides concentrations.
Objectives
We hypothesized that adjusting the concentration of N-terminal pro-B-type natriuretic peptide (NT-proBNP) for obesity could further increase its clinical utility in the early diagnosis of acute heart failure (AHF).
Methods and results
This hypothesis was tested in a prospective diagnostic study, enrolling unselected patients presenting to the emergency department with acute dyspnea. Two independent cardiologists/internists centrally adjudicated the final diagnosis using all individual patient information including cardiac imaging. NT-proBNP plasma concentrations were applied: first, using currently recommended cut-offs; second, using cut-offs lowered by 33% with body mass index (BMI) of 30-34.9kg/m2 and by 50% with BMI≥35kg/m2 . Among 2,038 patients, 509 (25%) were obese, of which 271 (53%) had AHF. The diagnostic accuracy of NT-proBNP as quantified by the area under the receiver-operating characteristics curve was lower in obese versus non-obese patients (0.890 vs 0.938). For rapid AHF rule-out in obese patients, the currently recommended cut-off of 300pg/mL achieved a sensitivity of 96.7% (95%CI 93.8-98.2%), ruling out 29% of patients, and missing 9 AHF patients. For the rapid AHF rule-in, the age-dependent cut-off concentrations (age<50years: 450pg/mL, age 50-75years: 900pg/mL, age>75years: 1,800pg/mL) achieved a specificity of 84.9% (95%CI, 79.8-88.9%). Proportionally lowering the currently recommended cut-offs by BMI increased sensitivity to 98.2% (95%CI 95.8-99.2%), missing 5 AHF patients, reduced the proportion of AHF patients remaining in the \"gray zone\" (48% versus 26%, p=0.002), achieving a specificity of 76.5% (95%CI 70.7-81.4%).
Conclusions
Adjusting NT-proBNP concentrations for obesity seems to further increase its clinical utility in the early diagnosis of AHF.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 18 Jul 2022; epub ahead of print
Kozhuharov N, Martin J, Wussler D, Lopez-Ayala P, ... Mueller C, BASEL V investigators
Eur J Heart Fail: 18 Jul 2022; epub ahead of print | PMID: 35851710
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Impact:
Abstract

Prognostic significance of obstructive coronary artery disease in patients admitted with acute decompensated heart failure: The ARIC study community surveillance.

Chunawala ZS, Qamar A, Arora S, Pandey A, ... Bhatt DL, Caughey MC
Aims
We aimed to investigate the impact of obstructive coronary artery disease (CAD) in patients with acute decompensated heart failure (ADHF), and examine potential differences in prognostic utility for heart failure with reduced versus preserved ejection fraction (HFrEF versus HFpEF, respectively).
Methods and results
The Atherosclerosis Risk in Communities study conducted hospital surveillance of ADHF from 2005-2014. Obstructive CAD was defined as ≥50% or ≥75% stenosis, respectively, for the left main and other major epicardial arteries. Adjusted associations between obstructive CAD and 30-, 60-, and 90-day mortality were analyzed. A total of 934 (4146 weighted) patients admitted with ADHF (mean age = 72 years, 46% women, 30% Black, 30% HFpEF) had available angiography (61% performed in-hospital). Obstructive CAD was more prevalent with HFrEF than HFpEF, whether at the left main (15% vs 11%), left anterior descending [LAD] (48% vs 30%), left circumflex (37% vs 32%), right coronary (42% vs 32%), or multiple coronary arteries (45% vs 33%). In-hospital revascularization was performed in 25% and 22% with HFrEF and HFpEF, respectively. Obstructive CAD was associated with higher adjusted mortality, particularly with left main or LAD involvement, and had a more pronounced association with 90-day mortality in HFrEF (OR = 2.77; 95% CI: 1.53 - 5.02) than HFpEF (OR = 0.94; 95% CI: 0.36 - 2.41); P-interaction = 0.05.
Conclusion
Patients hospitalized with ADHF and coexisting obstructive CAD have higher short-term mortality, warranting the need for effective interventions and secondary prevention. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 18 Jul 2022; epub ahead of print
Chunawala ZS, Qamar A, Arora S, Pandey A, ... Bhatt DL, Caughey MC
Eur J Heart Fail: 18 Jul 2022; epub ahead of print | PMID: 35851711
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Impact:
Abstract

Primary pericardial angiosarcoma in a patient with a history of colon carcinoma.

Kong LY, Cui XZ, Ma RC, Li L, ... Wang XJ, Liu F
Primary pericardial angiosarcoma is a rare but aggressive cause of cardiac tamponade. Development of pericardial angiosarcoma in patients with a history of carcinoma has not been reported previously. Imaging characteristics of pericardial angiosarcoma remain to be clarified, and hypoechoic mass interrupted with irregular hyperechoic tissue on transthoracic echocardiography may be a sign indicating neoplastic pericardial lesions. Herein, we report a case of histopathologically confirmed pericardial angiosarcoma in a 66-year-old man with a history of colon carcinoma. He died despite surgical pericardiectomy. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 18 Jul 2022; epub ahead of print
Kong LY, Cui XZ, Ma RC, Li L, ... Wang XJ, Liu F
Eur J Heart Fail: 18 Jul 2022; epub ahead of print | PMID: 35851982
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Impact:
Abstract

Use of guideline-recommended medical therapy in patients with heart failure and chronic kidney disease: from physician\'s prescriptions to patient\'s dispensations, medication adherence and persistence.

Janse RJ, Fu EL, Dahlström U, Benson L, ... Carrero JJ, Savarese G
Background
Half of heart failure (HF) patients have chronic kidney disease (CKD) complicating their pharmacological management. We evaluated physicians\' and patients\' patterns of use of evidence-based medical therapies in HF across CKD stages.
Methods
We studied HF patients with reduced (HFrEF) and mildly reduced (HFmrEF) ejection fraction enrolled in the Swedish Heart Failure register in 2009-2018. We investigated the likelihood of physicians to prescribe guideline-recommended therapies to patients with CKD, and of patients to fill the prescriptions within 90 days of incident HF (initiating therapy), to adhere (proportion of days covered≥80%) and persist (continued use) on these treatments during the first year of therapy.
Results
We identified 31,668 patients with HFrEF (median age 74 years, 46% CKD). The proportions receiving a prescription for ACEi/ARB/ARNi were 96%, 92%, 86%, and 68%, for eGFR≥60, 45-59, 30-44, and <30 mL/min/1.73m2 , respectively; for beta-blockers 94%, 93%, 92%, and 92%, for MRAs 45%, 44%, 37%, 24%; and for triple therapy (combination of ACEi/ARB/ARNi+BB+MRA) 38%, 35%, 28%, and 15%. Patients with CKD were less likely to initiate these medications, and less likely to adhere to and persist on ACEi/ARB/ARNi, MRA, and triple therapy. Among stoppers, CKD patients were less likely to restart these medications. Results were consistent after multivariable adjustment and in patients with HFmrEF (n=15,114).
Conclusions
Patients with HF and CKD are less likely to be prescribed and to fill prescriptions for evidence-based therapies, showing lower adherence and persistence, even at eGFR categories where these therapies are recommended and have shown efficacy in clinical trials. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 18 Jul 2022; epub ahead of print
Janse RJ, Fu EL, Dahlström U, Benson L, ... Carrero JJ, Savarese G
Eur J Heart Fail: 18 Jul 2022; epub ahead of print | PMID: 35851740
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Impact:
Abstract

Biomarker-driven prognostic models in chronic heart failure with preserved ejection fraction: the EMPEROR-Preserved trial.

Pocock SJ, Ferreira JP, Packer M, Zannad F, ... Butler J, Anker SD
Background
Biomarker-driven prognostic models incorporating NT-proBNP and hs-cTnT in HFpEF are lacking.
Aims
To generate a biomarker-driven prognostic tool for patients with chronic HFpEF enrolled in EMPEROR-Preserved.
Methods
Multivariable Cox regression models were created for (i) the primary composite outcome of HF hospitalization or cardiovascular death (ii) all-cause death (iii) cardiovascular death and (iv) HF hospitalization. PARAGON-HF was used as a validation cohort.
Results
NT-proBNP and hs-cTnT were the dominant predictors of the primary outcome, and in addition, a shorter time since last hospitalization, NYHA class III or IV, history of COPD, insulin-treated diabetes, low hemoglobin, and a longer time since HF diagnosis were key predictors (8 variables, all P<0.001). The consequent primary outcome risk score discriminated well (c-statistic=0.75) with patients in the top 10th of risk having an event rate >22x higher than those in the bottom 10th . A model for HF hospitalization alone had even better discrimination (c=0.79). Empagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure in patients across all risk levels. NT-proBNP and hs-cTnT were also the dominant predictors of all-cause and cardiovascular mortality followed by history of COPD, low albumin, older age, LVEF ≥50%, NYHA class III or IV and insulin-treated diabetes (8 variables, all P<0.001). The mortality risk model had similar discrimination for all-cause and cardiovascular mortality (c-statistic=0.72 for both). External validation provided c-statistics of 0.71, 0.71, 0.72, and 0.72 for the primary outcome, HF hospitalization alone, all-cause death, and cardiovascular death, respectively.
Conclusions
The combination of NT-proBNP and hs-cTnT along with a few readily available clinical variables provides effective risk discrimination both for morbidity and mortality in patients with HFpEF. A predictive toolkit facilitates the ready implementation of these risk models in routine clinical practice.

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Eur J Heart Fail: 07 Jul 2022; epub ahead of print
Pocock SJ, Ferreira JP, Packer M, Zannad F, ... Butler J, Anker SD
Eur J Heart Fail: 07 Jul 2022; epub ahead of print | PMID: 35796209
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Impact:
Abstract

Guideline-directed medical treatment in patients undergoing transcatheter edge-to-edge repair for secondary mitral regurgitation.

Higuchi S, Orban M, Adamo M, Giannini C, ... Hausleiter J, EuroSMR investigators
Introduction
Guideline-directed medical therapy (GDMT), based on the combination of beta blockers (BB), renin-angiotensin system inhibitors (RAS-I), and mineralocorticoid-receptor antagonists (MRA), is known to have a major impact on the outcome of the patients with heart failure with reduced ejection fraction (HFrEF). Although GDMT is recommended prior to M-TEER, not all patients tolerate it. We studied the association of GDMT prescription with survival in HFrEF patients undergoing mitral valve transcatheter edge-to-edge repair (M-TEER) for secondary mitral regurgitation (SMR).
Methods and results
EuroSMR, a European multicenter registry, included SMR patients with left ventricular ejection fraction of less than fifty percent. The outcome was 2-year all-cause mortality. Of 1344 patients, BB, RAS-I, and MRA were prescribed in 1169 (87%), 1012 (75%), and 765 (57%) patients at the time of M-TEER, respectively. Triple GDMT prescription was associated with a lower 2-year all-cause mortality compared to non-triple GDMT (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.60-0.91). The association persisted in patients with glomerular filtration rate of <30ml/min, ischemic etiology, or right ventricular dysfunction. Further, a positive impact of triple GDMT prescription on survival was observed in patients with residual MR of ≥2+ (HR, 0.62; 95% CI, 0.44-0.86), but not in patients with residual MR of ≤1+ (HR, 0.83; 95% CI, 0.64-1.08).
Conclusion
Triple GDMT prescription is associated with higher 2-year survival after M-TEER in HFrEF patients with SMR. This association was consistent also in patients with major comorbidities or non-optimal results after M-TEER.

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Eur J Heart Fail: 06 Jul 2022; epub ahead of print
Higuchi S, Orban M, Adamo M, Giannini C, ... Hausleiter J, EuroSMR investigators
Eur J Heart Fail: 06 Jul 2022; epub ahead of print | PMID: 35791663
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Impact:
Abstract

Baseline clinical characteristics of heart failure patients with reduced ejection fraction enrolled in the BUDAPEST-CRT Upgrade trial.

Merkely B, Gellér L, Zima E, Osztheimer I, ... Kovács A, Kosztin A
Aims
The BUDAPEST-CRT Upgrade study is the first prospective, randomized, multicentre clinical trial investigating the outcomes after cardiac resynchronization therapy (CRT) upgrade in heart failure (HF) patients with intermittent or permanent right ventricular pacing (RVP) with wide paced QRS. This report describes the baseline clinical characteristics of the enrolled patients and compares them to cohorts from previous milestone CRT studies.
Methods and results
This international multicentre randomized controlled trial investigates 360 patients having a pacemaker (PM) or implantable cardioverter defibrillator (ICD) device for at least six months prior to enrollment, reduced left ventricular ejection fraction (LVEF≤35%), HF symptoms (New York Heart Association functional class II-IVa), wide paced QRS (>150 ms), and ≥20% of RVP burden without having a native left bundle branch block. At enrollment, the mean age of the patients was 73±8 years; 89% were male, 97% of the patients were in NYHA II/III functional class, and 56% had atrial fibrillation. Enrolled patients predominantly had conventional PM devices, with a mean RVP burden of 86%. Thus, this is a patient cohort with advanced HF, low baseline LVEF (25%±7%), high N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels [2231 pg/mL (25th - 75th percentile 1254/4309 pg/mL)], and frequent HF hospitalizations during the preceding 12 months (50%).
Conclusion
When compared with prior CRT trial cohorts, the BUDAPEST-CRT Upgrade study includes older patients with a strong male predominance and a high burden of atrial fibrillation and other comorbidities. Moreover, this cohort represents an advanced HF population with low LVEFs, high NT-proBNPs, and frequent previous HF events.

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Eur J Heart Fail: 05 Jul 2022; epub ahead of print
Merkely B, Gellér L, Zima E, Osztheimer I, ... Kovács A, Kosztin A
Eur J Heart Fail: 05 Jul 2022; epub ahead of print | PMID: 35791276
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Impact:
Abstract

An international Delphi consensus regarding best practice recommendations for hyperkalaemia across the cardiorenal spectrum.

Burton JO, Coats AJ, Kovesdy CP, Palmer BF, ... Sood MM, Zieroth S
Aims
Renin-angiotensin-aldosterone system inhibitors (RAASi) are guideline recommended therapy for individuals with cardiorenal disease. They are associated with increased risk of hyperkalaemia, a common and life-threatening disorder for this population. RAASi-induced hyperkalaemia therapy often leads to dose reduction or discontinuation, reducing cardiorenal protection. Guideline recommendations differ between specialities for the clinical management of hyperkalaemia. Using a modified Delphi method, we developed consensus recommendations for optimal management of hyperkalaemia in adults with cardiorenal disease.
Methods and results
An international steering group of cardiologists and nephrologists developed 39 statements regarding hyperkalaemia care, including risk factors and risk stratification, prevention, correction, and cross-specialty coordination. Consensus was determined by agreement on an online questionnaire administered to cardiorenal specialists across Europe and North America. The threshold for consensus agreement was established a priori by the steering group at 67%. Across November 2021, 520 responses were received from Canada (n = 50), France (n = 50), Germany (n = 54), Italy (n = 58), Spain (n = 57), the UK (n = 49), and the U.S. (n = 202); 268 from cardiologists and 252 from nephrologists. Twenty-nine statements attained very high agreement (≥ 90%) and 10 attained high agreement (≥ 67-< 90%), with strong alignment between cardiologists and nephrologists.
Conclusion
A high degree of consensus regarding hyperkalaemia evaluation and management exists among healthcare professionals. Based on high levels of agreement, the steering group derived six key recommendations for hyperkalaemia prevention and management in people with cardiorenal disease. Future studies examining the quality of hyperkalaemia care delivery are required.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 05 Jul 2022; epub ahead of print
Burton JO, Coats AJ, Kovesdy CP, Palmer BF, ... Sood MM, Zieroth S
Eur J Heart Fail: 05 Jul 2022; epub ahead of print | PMID: 35791065
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Impact:
Abstract

Efficacy and Safety of Vericiguat in Patients with Heart Failure with Reduced Ejection Fraction Treated with Sacubitril/Valsartan: Insights from the VICTORIA Trial.

Senni M, Alemayehu WG, Sim D, Edelmann F, ... Armstrong PW, VICTORIA Study Group
Purpose
We assessed a subset of the 5040 patients in VICTORIA receiving sacubitril/valsartan, either at randomization (n=731) or post-randomization drop-in use (n=425), to evaluate the relationship between the efficacy and safety of combination therapy with vericiguat.
Methods and results
The efficacy of vericiguat on the primary composite endpoint, heart failure (HF) hospitalization, and all-cause mortality was assessed. Safety outcomes included symptomatic hypotension, syncope, worsening renal function, and hyperkalemia. At randomization, 731 patients received sacubitril/valsartan; they were more frequently from Western Europe or North America, had lower ejection fraction and systolic blood pressures, and more use of triple background HF therapy (65.9 vs. 58.6%), biventricular pacemakers (17.9 vs 14.1%), or implantable cardioverter defibrillators (42.3 vs 25.3%). For patients on versus not on sacubitril/valsartan at randomization, adjusted HRs (95% CIs) for vericiguat\'s treatment effect on the primary composite outcome, cardiovascular death, and HF hospitalization were 0.92 (0.71-1.19) vs. 0.89 (0.80-0.98), 0.71 (0.45-1.12) vs. 0.95 (0.82-1.11), and 0.98 (0.74-1.29) vs. 0.87 (0.78-0.98), respectively. No significant interaction existed between sacubitril/valsartan and vericiguat\'s treatment effect (p-values for interaction: 0.81, 0.23 and 0.47, respectively). Post-randomization, more drop-in sacubitril/valsartan use occurred in those assigned placebo (n=238) versus vericiguat (n=187) (p=0.007). Symptomatic hypotension (21.0 vs 23.1%; p=0.41), renal dysfunction (29.9 vs 31.9.0%; p=0.50), and hyperkalemia (10.3 vs 7.9%; p=0.20) in patients receiving sacubitril/valsartan (n=992) for ≥3 months were not different by treatment arm.
Conclusions
Concomitant use of sacubitril/valsartan for at least 3 months did not alter the efficacy of vericiguat and was similarly safe and tolerated in both study arms. Sacubitril/valsartan was initiated more frequently after randomization in patients assigned to placebo versus vericiguat.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 05 Jul 2022; epub ahead of print
Senni M, Alemayehu WG, Sim D, Edelmann F, ... Armstrong PW, VICTORIA Study Group
Eur J Heart Fail: 05 Jul 2022; epub ahead of print | PMID: 35791083
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Impact:
Abstract

Midazolam versus morphine in acute cardiogenic pulmonary oedema: results of a multicenter, open-label, randomized controlled trial.

Domínguez-Rodríguez A, Suero-Mendez C, Burillo-Putze G, Gil V, ... Miró Ò, MIMO (MIdazolam versus MOrphine) Trial Investigators
Aims
Benzodiazepines have been used as safe anxiolytic drugs for decades and some authors have suggested they could be an alternative for morphine for treating acute cardiogenic pulmonary edema (ACPE). We compared the efficacy and safety of midazolam and morphine in patients with ACPE.
Methods and results
A randomized, multicenter, open-label, blinded endpoint clinical trial was performed in 7 Spanish emergency departments (EDs). Patients >18 years old clinically diagnosed with ACPE and with dyspnea and anxiety were randomized (1:1) at ED arrival to receive either intravenous midazolam or morphine. Efficacy was assessed by in-hospital all-cause mortality (primary endpoint). Safety was assessed through serious adverse event (SAE) reporting, and composite endpoint included 30-day mortality and SAE. Analyses were made on an intention-to-treat basis. The trial was stopped early after a planned interim analysis by the safety monitoring committee. At that time, 111 patients had been randomized: 55 to midazolam and 56 to morphine. There were no statistically significantly differences in primary endpoint (in-hospital mortality for midazolam/morphine 12.7%/17.9%, Risk Ratio[RR], 0.71; 95% confidence interval[CI], 0.29 to 1.74; P=0.60). SAE were less common with midazolam (18.2%/42.9%, RR, 0.42; 95%CI, 0.22 to 0.80; P=0.007), as were the composite safety endpoint (23.6%/44.6%, RR, 0.53; 95% CI, 0.30 to 0.92; P=0.03).
Conclusion
Although the number of patients was too small to draw final conclusions and there were no significant differences in mortality between midazolam and morphine, a significantly higher rate of SAEs was found in the morphine group.

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Eur J Heart Fail: 03 Jul 2022; epub ahead of print
Domínguez-Rodríguez A, Suero-Mendez C, Burillo-Putze G, Gil V, ... Miró Ò, MIMO (MIdazolam versus MOrphine) Trial Investigators
Eur J Heart Fail: 03 Jul 2022; epub ahead of print | PMID: 35780488
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Impact:
Abstract

BLITZ-HF: a nationwide initiative to evaluate and improve adherence to acute and chronic heart failure guidelines.

Gulizia MM, Orso F, Mortara A, Lucci D, ... Oliva F, BLITZ-HF Investigators
Aims
To assess adherence to guideline recommendations among a large network of Italian cardiology sites in the management of acute and chronic heart failure and to evaluate if an ad-hoc educational intervention is able to improve their performance on several pharmacological and non-pharmacological indicators.
Methods and results
BLITZ-HF was a cross-sectional study based on a web based recording system with pop-up reminders on guideline recommendations used during two three-month enrolment periods carried out 3 months apart (phase 1 and 3), interspersed by face-to-face macro-regional benchmark analyses and educational meetings (phase 2). Overall, 7218 patients with acute and chronic HF were enrolled at 106 cardiology sites. During the enrolment phases, 3920 and 3298 patients were included respectively, 84% with CHF and 16% with AHF in phase 1 while 74% with CHF and 26% with AHF in phase 3. At baseline, adherence to guideline recommendations was already overall high for most indicators. Among AHF patients an improvement was obtained in three of eight indicators, with a significant rise in echocardiographic evaluation. Among CHF patients with HFpEF or HFmrEF, performance increased in two of three indicators: creatinine and echocardiographic evaluations. An overall performance improvement was observed in six of nine indicators in ambulatory HFrEF patients with a significant increase in ARNI prescription rates.
Conclusions
Within a context of an already elevated level of adherence to HF guideline recommendations, a structured multifaceted educational intervention could be useful to improve performance on specific indicators. Extending this approach to other non-cardiology healthcare professionals, who usually manage patients with HF, should be considered. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 03 Jul 2022; epub ahead of print
Gulizia MM, Orso F, Mortara A, Lucci D, ... Oliva F, BLITZ-HF Investigators
Eur J Heart Fail: 03 Jul 2022; epub ahead of print | PMID: 35785461
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Impact:
Abstract

Progression of echocardiographic parameters and prognosis in ATTR cardiac amyloidosis.

Chacko L, Karia N, Venneri L, Bandera F, ... Gillmore JD, Fontana M
Aims
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly diagnosed disease. Echocardiography is widely utilized, but studies to confirm the value of echocardiography for tracking changes over time are not available. We sought to describe: (1) changes in multiple echocardiographic parameters; (2) differences in rate of progression of three predominant genotypes; and (3) the ability of changes in echocardiographic parameters to predict prognosis.
Methods and results
We prospectively studied 877 ATTR-CM patients attending our centre between 2000 and 2020. Serial echocardiography findings at baseline, 12-months and 24-months were compared with survival. Five-hundred-and-sixty-five patients had wild-type ATTR-CM and 312 hereditary ATTR-CM (201 with V122I; 90 with T60A).There was progressive worsening of structural and functional parameters over time, patients with V122I ATTR-CM showing more rapid worsening of left and right ventricular structural and functional parameters compared to both wild-type and T60A ATTR-CM. Among a wide range of echocardiographic analyses, including deformation-based parameters, only worsening in the degree of mitral and tricuspid regurgitation (MR and TR) at 12-and 24 month assessments was associated with worse prognosis (change at 12-months: MR, hazard ratio 1.43 (1.14-1.80,p=0.002); TR, hazard ratio 1.38 (1.10-1.75,p=0.006). Worsening in MR remained independently associated with poor prognosis after adjusting for known predictors.
Conclusion
In ATTR-CM, echocardiographic parameters progressively worsen over time. Patients with V122I ATTR-CM demonstrate the most rapid deterioration. Worsening of MR and TR were the only parameters associated with mortality, MR remaining independent after adjusting for known predictors. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 02 Jul 2022; epub ahead of print
Chacko L, Karia N, Venneri L, Bandera F, ... Gillmore JD, Fontana M
Eur J Heart Fail: 02 Jul 2022; epub ahead of print | PMID: 35779241
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Abstract

A global perspective on the management and outcomes of peripartum cardiomyopathy: a systematic review and meta-analysis.

Hoevelmann J, Engel ME, Muller E, Hohlfeld A, ... Sliwa K, Viljoen C
Aims
Peripartum cardiomyopathy (PPCM) remains a major contributor to maternal morbidity and mortality worldwide. The disease is associated with various complications occurring mainly early during its course. Reported adverse outcomes include decompensated heart failure, thromboembolic complications, arrhythmias and death. We sought to systematically and comprehensively review published literature on the management, and outcome of women with PPCM across different geographical regions and to identify possible predictors of adverse outcomes.
Methods and results
We performed a comprehensive search of relevant literature (2000 to June 2021) across a number of electronic databases. Cohort, case-control and cross-sectional studies, as well as control arms of randomised controlled trials reporting on six- and/or twelve-month outcomes of PPCM were considered eligible (PROSPERO registration: CRD42021255654). Forty-seven studies (4875 patients across 60 countries) met the inclusion criteria. Haemodynamic and echocardiographic parameters were similar across all continents. All-cause mortality was 8.0% [95% CI 5.5-10.8, I2 =79.1%) at six months and 9.8% [95% CI 6.2-14.0], I2 =80.5%) at twelve months, respectively. All-cause mortality was highest in Africa and Asia/Pacific. Overall, 44.1% ([95% CI 36.1-52.2], I2 =91.7%) of patients recovered their LV function within six months and 58.7% ([95% CI 48.1-68.9], I2 =75.8%) within twelve months, respectively. Europe and North America reported the highest prevalence of LV recovery. Frequent prescription of beta-blocker, ACE-I/ARB and bromocriptine/cabergoline were associated with significantly lower all-cause mortality and better LV recovery.
Conclusion
We identified significant global differences in six- and twelve-month outcomes in women with PPCM. Frequent prescription of guideline-directed heart failure therapy was associated with better LV recovery and lower all-cause mortality. Timely initiation and up-titration of heart failure therapy should therefore be strongly encouraged to improve outcome in PPCM. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 02 Jul 2022; epub ahead of print
Hoevelmann J, Engel ME, Muller E, Hohlfeld A, ... Sliwa K, Viljoen C
Eur J Heart Fail: 02 Jul 2022; epub ahead of print | PMID: 35778990
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Abstract

Catheter Ablation for Patients with Atrial Fibrillation and Heart Failure: Insights from the Swedish Heart Failure Registry.

von Olshausen G, Benson L, Dahlström U, Lund LH, Savarese G, Braunschweig F
Aims
To investigate the association between catheter ablation for atrial fibrillation (AF) and mortality as well as hospitalization for heart failure (HF) in patients with HF across the ejection fraction (EF) spectrum.
Methods
Patients with first-time catheter ablation for AF (ablation group) compared to only medical treated AF patients (no ablation group) were identified from the Swedish Heart Failure Registry between 2005 and 2019. The primary outcome (all-cause mortality/first HF hospitalization) was assessed by Cox regression models in a 1:2 propensity score (PS) matched cohort and pre-specified EF subgroups (preserved EF [HFpEF] [EF≥50%], mildly reduced EF [HFmrEF] [EF 40% to 49%], reduced EF [HFrEF] [EF<40%]) of this cohort.
Results
452 patients in the ablation and 43766 patients in the no ablation group were identified. After PS matching, 434 patients in the ablation group were compared to 868 patients in the no ablation group. Over a median follow-up of 2.6 years (min. 0.0 years - max. 14.1 years), catheter ablation was associated with a lower risk of the primary outcome (all-cause mortality/first HF hospitalization) (Hazard ratio [HR] 0.78 [95%CI,0.65-0.94]). Results were consistent across all EF subgroups. In HFpEF, catheter ablation was also associated with a lower risk of recurrent HF hospitalization (Incidence rate ratio [IRR] 0.17 [95%CI,0.07-0.42]).
Conclusion
In HF patients across the EF spectrum, catheter ablation for AF was associated with lower risk of the primary outcome (all-cause mortality/first HF hospitalization). This study supports catheter ablation as a treatment option for AF in HF patients, including those with HFpEF. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 02 Jul 2022; epub ahead of print
von Olshausen G, Benson L, Dahlström U, Lund LH, Savarese G, Braunschweig F
Eur J Heart Fail: 02 Jul 2022; epub ahead of print | PMID: 35779270
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Abstract

Exercise Testing in HFpEF: an Appraisal Through Diagnosis, Pathophysiology and Therapy A Clinical Consensus Statement of the Heart Failure Association (HFA) and European Association of Preventive Cardiology (EAPC) of the European Society of Cardiology (ESC).

Marco Guazzi M, Wilhelm M, Halle M, Van Craenenbroeck E, ... Filippatos G, Pieske B
Patients with heart failure with preserved ejection fraction (HFpEF) universally complain of exercise intolerance and dyspnoea as key clinical correlates. Cardiac as well as extracardiac components play a role for the limited exercise capacity, including an impaired cardiac and peripheral vascular reserve, a limitation in mechanical ventilation and/or gas exchange with reduced pulmonary vascular reserve, skeletal muscle dysfunction and iron deficiency/anaemia. Although most of these components can be differentiated and quantified through gas exchange analysis by cardiopulmonary exercise testing (CPET), the information provided by objective measures of exercise performance have not been systematically considered in the recent algorithms/scores for HFpEF diagnosis, neither by European nor US groups. The current Clinical Consensus Statement by the HFA and EAPC Association of the ESC aims at outlining the role of exercise testing and its pathophysiological, clinical and prognostic insights, addressing the implication of a thorough functional evaluation from the diagnostic algorithm to the pathophysiology and treatment perspectives of HFpEF. Along with these goals, we provide a specific analysis on the evidence that CPET is the standard for assessing, quantifying, and differentiating the origin of dyspnoea and exercise impairment and even more so when combined with echo and/or invasive hemodynamic evaluation is here provided. This will lead to improved quality of diagnosis when applying the proposed scores and may also help useful to implement the progressive characterization of the specific HFpEF phenotypes, a critical step toward the delivery of phenotype-specific treatments.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 01 Jul 2022; epub ahead of print
Marco Guazzi M, Wilhelm M, Halle M, Van Craenenbroeck E, ... Filippatos G, Pieske B
Eur J Heart Fail: 01 Jul 2022; epub ahead of print | PMID: 35775383
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Abstract

A PILOT CLINICAL TRIAL OF CELL THERAPY IN HEART FAILURE WITH PRESERVED EJECTION FRACTION.

Vrtovec B, Frljak S, Poglajen G, Zemljic G, ... Haddad F, Wu JC
Aims
We investigated the effects of CD34+ cell therapy in patients with heart failure with preserved ejection fraction (HFpEF).
Methods and results
In a prospective pilot study, we enrolled 30 patients with HFpEF. In Phase 1, patients were treated with medical therapy for 6 months. Thereafter, all patients underwent CD34+ cell transplantation. Using electroanatomical mapping, we measured local mechanical diastolic delay and myocardial viability to guide the targeting of cell injections. Patients were followed for 6 months after cell transplantation (Phase 2), and the primary end-point was the difference in change in E/e\' between Phase 1 and Phase 2. In Phase 1, the decrease in E/e\' was significantly less pronounced than in Phase 2. (-0.33±1.72 vs. -3.77±2.66, P=0.001). During Phase 1, there was no significant change in global systolic strain (GLS; from -12.5±2.4% to -12.8±2.6%, P=0.77), NT-proBNP (from 1463±1247 pg/mL to 1298±931 pg/mL, P=0.31), or 6-minute walk test distance (6MWT; from 391±75 m to 402±93 m, P=0.42). In Phase 2, an improvement was noted in NT-proBNP (from 1298±931 pg/ml to 887±809 pg/ml, P=0.02) and 6MWT (from 402±93 m to 438±72 m, P=0.02). Although GLS did not change significantly in Phase 2 (from -12.8±2.6% to -13.8±2.7%, P=0.36), we found improved local systolic strain at cell injection sites (-3.4±6.8%, P=0.005).
Conclusions
In this non-randomized trial, transendocardial CD34+ cell therapy in HFpEF was associated with an improvement in E/e\', NT-proBNP, exercise capacity, and local myocardial strain at the cell injection sites.
Clinical trials registration
Clinicaltrials.gov NCT02923609 This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Eur J Heart Fail: 01 Jul 2022; epub ahead of print
Vrtovec B, Frljak S, Poglajen G, Zemljic G, ... Haddad F, Wu JC
Eur J Heart Fail: 01 Jul 2022; epub ahead of print | PMID: 35775390
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This program is still in alpha version.