Publications by authors named "Gerasimos Filippatos"

574 Publications

The effect of intravenous ferric carboxymaltose on health-related quality of life in iron-deficient patients with acute heart failure: the results of the AFFIRM-AHF study.

Eur Heart J 2021 Jun 3. Epub 2021 Jun 3.

Robertson Center for Biostatistics, University of Glasgow, Boyd Orr Building University Avenue, Glasgow G12 8QQ, UK.

Aims: Patients with heart failure (HF) and iron deficiency experience poor health-related quality of life (HRQoL). We evaluated the impact of intravenous (IV) ferric carboxymaltose (FCM) vs. placebo on HRQoL for the AFFIRM-AHF population.

Methods And Results: The baseline 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which was completed for 1058 (535 and 523) patients in the FCM and placebo groups, respectively, was administered prior to randomization and at Weeks 2, 4, 6, 12, 24, 36, and 52. The baseline KCCQ-12 overall summary score (OSS) mean ± standard error was 38.7 ± 0.9 (FCM group) and 37.1 ± 0.8 (placebo group); corresponding values for the clinical summary score (CSS) were 40.9 ± 0.9 and 40.1 ± 0.9. At Week 2, changes in OSS and CSS were similar for FCM and placebo. From Week 4 to Week 24, patients assigned to FCM had significantly greater improvements in OSS and CSS scores vs. placebo [adjusted mean difference (95% confidence interval, CI) at Week 4: 2.9 (0.5-5.3, P = 0.018) for OSS and 2.8 (0.3-5.3, P = 0.029) for CSS; adjusted mean difference (95% CI) at Week 24: 3.0 (0.3-5.6, P = 0.028) for OSS and 2.9 (0.2-5.6, P = 0.035) for CSS]. At Week 52, the treatment effect had attenuated but remained in favour of FCM.

Conclusion: In iron-deficient patients with HF and left ventricular ejection fraction ≤50% who had stabilized after an episode of acute HF, treatment with IV FCM, compared with placebo, results in clinically meaningful beneficial effects on HRQoL as early as 4 weeks after treatment initiation, lasting up to Week 24.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehab234DOI Listing
June 2021

Concentration-dependent clinical and prognostic importance of high-sensitivity cardiac troponin T in heart failure and a reduced ejection fraction and the influence of empagliflozin: the EMPEROR-Reduced trial.

Eur J Heart Fail 2021 May 30. Epub 2021 May 30.

Université de Lorraine, Inserm INI-CRCT, CHRU, Nancy, France.

Aims: Circulating troponin is an important measure of risk in patients with heart failure, but it has not been used to determine if disease severity influences the responses to drug treatments in randomized controlled trials.

Methods And Results: In the EMPEROR-Reduced trial, patients with class II-IV heart failure and a reduced ejection fraction were randomly assigned to placebo or empagliflozin 10 mg daily and followed for the occurrence of serious heart failure and renal events. High-sensitivity cardiac troponin T (hs-cTnT) was measured in 3636 patients (>97%) at baseline, and patients were divided into four groups based on the degree of troponin elevation. With increasing concentrations of hs-cTnT, patients were progressively more likely to have diabetes and atrial fibrillation, to have New York Heart Association class III-IV symptoms and been hospitalized for heart failure within the prior year, and to have elevated levels of natriuretic peptides and worse renal function (P-trend < 0.0001 for all comparisons), but importantly, the troponin groups did not differ with respect to ejection fraction. A linear relationship was observed between the logarithm of hs-cTnT and the combined risk of cardiovascular death or hospitalization for heart failure (P = 0.0015). When treated with placebo, patients with the highest levels of hs-cTnT had risks of cardiovascular death and hospitalization for heart failure that were 3-5 fold greater than those with values in the normal range. Patients with higher levels of hs-cTnT were also more likely to experience worsening of renal function and serious adverse renal events and showed the least improvement in health status (as measured by the Kansas City Cardiomyopathy Questionnaire). When compared with placebo, empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure, regardless of the baseline level of hs-cTnT, whether the effects of treatment were analysed as hazard ratios or absolute risk reductions.

Conclusions: Elevations in hs-cTnT reflect the clinical severity, stability and prognosis of patients with heart failure and a reduced ejection fraction, with biomarkers, comorbidities, clinical course and risks that are proportional to the magnitude of hs-cTnT elevation. Empagliflozin exerted favourable effects on heart failure and renal outcomes, regardless of the baseline concentration of hs-cTnT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2256DOI Listing
May 2021

HFA/HFSA/JHFS Position Statement on Endomyocardial Biopsy.

J Card Fail 2021 Apr 27. Epub 2021 Apr 27.

Cleveland Clinic, Cleveland OH, USA.

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant (HTx) rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples has significantly improved diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: 1) an overview of the practical approach to EMB, 2) an update on indications for EMB, 3) a revised plan for HTx rejection surveillance, 4) the impact of multimodality imaging on EMB, and 5) the current clinical practice in the worldwide use of EMB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cardfail.2021.04.010DOI Listing
April 2021

Finerenone Reduces Onset of Atrial Fibrillation in Patients with Chronic Kidney Disease and Type 2 Diabetes.

J Am Coll Cardiol 2021 May 4. Epub 2021 May 4.

Department of Cardiology (CVK), and Berlin Institute of Health Center for Regenerative Therapies, German Centre for Cardiovascular Research Partner Site Berlin, Charité Universitätsmedizin, Berlin, Germany.

Background: Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) are at risk of atrial fibrillation or flutter (AFF) due to cardiac remodeling and kidney complications. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, inhibited cardiac remodeling in preclinical models.

Objectives: To examine the effect of finerenone on new-onset AFF and cardiorenal effects by history of AFF in FIDELIO-DKD.

Methods: Patients with CKD and T2D were randomized (1:1) to finerenone or placebo. Eligible patients had a urine albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g, an estimated glomerular filtration rate (eGFR) ≥25 to <75 ml/min/1.73 m and received optimized doses of renin-angiotensin system blockade. Effect on new-onset AFF was evaluated as a prespecified outcome adjudicated by an independent cardiologist committee. The primary composite outcome (kidney failure, sustained ≥40% decrease in eGFR from baseline, or renal death) and key secondary outcome (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) were analyzed by history of AFF.

Results: Of 5,674 patients, 461 (8.1%) had a history of AFF. New-onset AFF occurred in 82 (3.2%) patients on finerenone and 117 (4.5%) on placebo (hazard ratio: 0.71; 95% confidence interval: 0.53 to 0.94; p = 0.016). The effect of finerenone on primary and key secondary kidney and cardiovascular outcomes was not significantly impacted by baseline AFF (interaction p value: 0.16 and 0.85, respectively).

Conclusions: In patients with CKD and T2D, finerenone reduced the risk of new-onset AFF. The risk of kidney or cardiovascular events was reduced irrespective of history of AFF at baseline.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2021.04.079DOI Listing
May 2021

Heart Failure Association of the ESC, Heart Failure Society of America and Japanese Heart Failure Society Position statement on endomyocardial biopsy.

Eur J Heart Fail 2021 May 19. Epub 2021 May 19.

Cleveland Clinic, Cleveland, OH, USA.

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant (HTx) rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples have significantly improved diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (i) an overview of the practical approach to EMB, (ii) an update on indications for EMB, (iii) a revised plan for HTx rejection surveillance, (iv) the impact of multimodality imaging on EMB, and (v) the current clinical practice in the worldwide use of EMB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2190DOI Listing
May 2021

Neutrophil-to-lymphocyte ratio and outcomes in patients with new-onset or worsening heart failure with reduced and preserved ejection fraction.

ESC Heart Fail 2021 May 16. Epub 2021 May 16.

Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK.

Aims: Inflammation is thought to play a role in heart failure (HF) pathophysiology. Neutrophil-to-lymphocyte ratio (NLR) is a simple, routinely available measure of inflammation. Its relationship with other inflammatory biomarkers and its association with clinical outcomes in addition to other risk markers have not been comprehensively evaluated in HF patients.

Methods: We evaluated patients with worsening or new-onset HF from the BIOlogy Study to Tailored Treatment in Chronic Heart Failure (BIOSTAT-CHF) study who had available NLR at baseline. The primary outcome was time to all-cause mortality or HF hospitalization. Outcomes were validated in a separate HF population.

Results: 1622 patients were evaluated (including 523 ventricular ejection fraction [LVEF] < 40% and 662 LVEF ≥ 40%). NLR was significantly correlated with biomarkers related to inflammation as well as NT-proBNP. NLR was significantly associated with the primary outcome in patients irrespective of LVEF (hazard ratio [HR] 1.18 per standard deviation increase; 95% confidence interval [CI] 1.11-1.26, P < 0.001). Patients with NLR in the highest tertile had significantly worse outcome than those in the lowest independent of LVEF (<40%: HR 2.75; 95% CI 1.84-4.09, P < 0.001; LVEF ≥ 40%: HR 1.51; 95% CI 1.05-2.16, P = 0.026). When NLR was added to the BIOSTAT-CHF risk score, there were improvements in integrated discrimination index (IDI) and net reclassification index (NRI) for occurrence of the primary outcome (IDI + 0.009; 95% CI 0.00-0.019, P = 0.030; continuous NRI + 0.112, 95% CI 0.012-0.176, P = 0.040). Elevated NLR was similarly associated with adverse outcome in the validation cohort. Decrease in NLR at 6 months was associated with reduced incidence of the primary outcome (HR 0.75; 95% CI 0.57-0.98, P = 0.036).

Conclusions: Elevated NLR is significantly associated with elevated markers of inflammation in HF patients and is associated with worse outcome. Elevated NLR might potentially be useful in identifying high-risk HF patients and may represent a treatment target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ehf2.13424DOI Listing
May 2021

Association between up-titration of medical therapy and total hospitalizations and mortality in patients with recent worsening heart failure across the ejection fraction spectrum.

Eur J Heart Fail 2021 May 16. Epub 2021 May 16.

National and Kapodistrian University of Athens, Department of Cardiology, Heart Failure Unit, Attikon University Hospital, Athens, Greece.

Background: The role of neurohormonal inhibition in chronic heart failure (HF) is well established. There are limited data on the effect of up-titration of renin-angiotensin inhibitors (RASi) and beta-blockers (BBs) on clinical outcomes of patients with worsening HF across the left ventricular ejection fraction (LVEF) spectrum.

Methods And Results: We analysed data from 2345 patients from BIOSTAT-CHF (80.9% LVEF <40%), who completed a 3-month up-titration period after recent worsening of HF. Patients were classified by achieved dose (% of recommended): ≥100%, 50-99%, 1-49%, and none. Recurrent event analysis using joint and shared frailty models was used to examine the association between RASi/BB dose and all-cause and HF hospitalizations. In the 21 months following up-titration, 512 patients died and 879 (37.5%) had ≥1 hospitalization. RASi up-titration was associated, incrementally, with reduced risk of all-cause hospitalization at all achieved dose levels compared to no treatment [hazard ratio (95% confidence interval): ≥100%: 0.60 (0.49-0.74), P < 0.001; 50-99%: 0.56 (0.46-0.68), P < 0.001; 1-49%: 0.71 (0.59-0.86), P < 0.001]. This association was consistent up to an LVEF of 49% (P < 0.001), and when considering only HF hospitalizations. Up-titration of BBs was associated with fewer all-cause hospitalizations only when LVEF was <40% (overall P < 0.001), but with more HF hospitalizations when LVEF was ≥50%. Up-titration of both RASi/BBs was associated with lower mortality in LVEF up to 49%.

Conclusion: After recent worsening of HF, up-titration of RASi and BBs was associated with a better prognosis in patients with LVEF ≤49%. Up-titration of BBs was associated with a greater risk of HF hospitalization when LVEF was ≥50%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2219DOI Listing
May 2021

Percutaneous Mitral Valve Annuloplasty in Patients With Secondary Mitral Regurgitation and Severe Left Ventricular Enlargement.

JACC Heart Fail 2021 Jun 12;9(6):453-462. Epub 2021 May 12.

Department of Medicine, University of Mississippi School of Medicine, Jackson, Mississippi, USA.

Objectives: This study sought to determine the effect of percutaneous mitral valve annuloplasty with the Carillon device versus guideline-directed medical therapy (GDMT) alone in patients with secondary mitral regurgitation (MR) and severe left ventricular (LV) enlargement.

Background: The clinical impact of the Carillon device in patients with severe LV dilation is not well established.

Methods: This is a pooled analysis involving 3 prospective trials (TITAN [Transcatheter Implantation of Carillon Mitral Annuloplasty Device], TITAN II, and REDUCE FMR [CARILLON Mitral Contour System for Reducing Functional Mitral Regurgitation] trials) in which patients with functional MR and severe LV enlargement (LV end-diastolic diameter >65 mm) were treated with GDMT and the Carillon device versus GDMT alone. Key outcomes of this analysis were changes over 1 year of follow-up in mitral valve and LV echocardiographic parameters, functional outcome, quality of life, mortality, and heart failure hospitalization (HFH).

Results: A total of 95 patients (67 in the Carillon group, 28 in the GDMT group) with severe LV enlargement were included. In the Carillon group, all mitral valve and LV morphology parameters were significantly improved at 1 year. Regurgitant volume decreased by 12 ml (p < 0.001), MR grade decreased by 0.6 U (p < 0.001), LV end-diastolic volume decreased by 25 cm (p = 0.005), and LV end-systolic volume decreased by 21 cm (p = 0.01). Significant functional improvement differences were also noted between the Carillon group and the GDMT group including an improvement of Kansas City Cardiomyopathy Questionnaire score (15 ± 4 vs. 6 ± 6; p = 0.03). The incidence of HFH was 29.9% versus 50.0% and the cumulative rate of HFH was 0.43 versus 0.75 (p < 0.001).

Conclusions: In patients with functional MR and severe LV enlargement, the Carillon device improved mitral valve function, LV morphology, and functional outcome compared with patients receiving GDMT only. Preoperative LV dimension should not be a limiting factor when evaluating patient eligibility or anticipated response to therapy with the Carillon device.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchf.2021.03.002DOI Listing
June 2021

Perceived risk profile and treatment optimization in heart failure: an analysis from BIOlogy Study to TAilored Treatment in chronic heart failure.

Clin Cardiol 2021 Jun 7;44(6):780-788. Epub 2021 May 7.

Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Nancy, France.

Background: Achieving target doses of angiotensin-converting-enzyme inhibitor/angiotensin-receptor blockers (ACEi/ARB) and beta-blockers in heart failure with reduced ejection fraction (HFrEF) is often underperformed. In BIOlogy Study to TAilored Treatment in chronic heart failure (BIOSTAT-CHF) study, many patients were not up-titrated for which no clear reason was reported. Therefore, we hypothesized that perceived-risk profile might influence treatment optimization.

Methods: We studied 2100 patients with HFrEF (LVEF≤40%) to compare the clinical characteristics and adverse events associated with treatment up-titration (after a 3-month titration protocol) between; a) patients not reaching target doses for unclear reason; b) patients not reaching target doses due to symptoms and/or side effects; c) patients reaching target doses.

Results: For ACEi/ARB, (a), (b) and (c) was observed in 51.3%, 25.9% and 22.7% of patients, respectively. For beta-blockers, (a), (b) and (c) was observed in 67.5%, 20.2% and 12.3% of patients, respectively. By multinomial logistic regression analysis for ACEi/ARB, patients in group (a) and (b) had lower blood pressure and poorer renal function, and patients in group (a) were older and had lower ejection fraction. For beta-blockers, patients in group (a) and (b) had more severe congestion and lower heart rate. At 9 months, adverse events (i.e., hypotension, bradycardia, renal impairment, and hyperkalemia) occurred similarly among the three groups.

Conclusions: Patients in whom clinicians did not give a reason why up-titration was missed were older and had more co-morbidities. Patients in whom up-titration was achieved did not have excess adverse events. However, from these observational findings, the pattern of subsequent adverse events among patients in whom up-titration was missed cannot be determined.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/clc.23576DOI Listing
June 2021

Patient profiling in heart failure for tailoring medical therapy. A consensus document of the Heart Failure Association of the European Society of Cardiology.

Eur J Heart Fail 2021 May 1. Epub 2021 May 1.

Department Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

Despite guideline recommendations and available evidence, implementation of treatment in heart failure (HF) is poor. The majority of patients are not prescribed drugs at target doses that have been proven to positively impact morbidity and mortality. Among others, tolerability issues related to low blood pressure, heart rate, impaired renal function or hyperkalaemia are responsible. Chronic kidney disease plays an important role as it affects up to 50% of patients with HF. Also, dynamic changes in estimated glomerular filtration rate may occur during the course of HF, resulting in inappropriate dose reduction or even discontinuation of decongestive or neurohormonal modulating therapy in clinical practice. As patients with HF are rarely naïve to pharmacologic therapies, the challenge is to adequately prioritize or select the most appropriate up-titration schedule according to patient profile. In this consensus document, we identified nine patient profiles that may be relevant for treatment implementation in HF patients with a reduced ejection fraction. These profiles take into account heart rate (<60 bpm or >70 bpm), the presence of atrial fibrillation, symptomatic low blood pressure, estimated glomerular filtration rate (<30 or >30 mL/min/1.73 m ) or hyperkalaemia. The pre-discharge patient, frequently still congestive, is also addressed. A personalized approach, adjusting guideline-directed medical therapy to patient profile, may allow to achieve a better and more comprehensive therapy for each individual patient than the more traditional, forced titration of each drug class before initiating treatment with the next.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2206DOI Listing
May 2021

Serum uric acid and outcomes in patients with chronic heart failure through the whole spectrum of ejection fraction phenotypes: Analysis of the ESC-EORP Heart Failure Long-Term (HF LT) Registry.

Eur J Intern Med 2021 Apr 22. Epub 2021 Apr 22.

EURObservational Research Programme, European Society of Cardiology, Biot, France; Maria Cecilia Hospital, GVM Care&Research, Cotignola, Italy.

Background: Retrospective analyses of clinical trials indicate that elevated serum uric acid (sUA) predicts poor outcome in heart failure (HF). Uric acid can contribute to inflammation and microvascular dysfunction, which may differently affect different left ventricular ejection fraction (LVEF) phenotypes. However, role of sUA across LVEF phenotypes is unknown.

Objectives: We investigated sUA association with outcome in a prospective cohort of HF patients stratified according to LVEF.

Methods: Through the Heart Failure Long-Term Registry of the European Society of Cardiology (ESC-EORP-HF-LT), 4,438 outpatients were identified and classified into: reduced (<40% HFrEF), mid-range (40-49% HFmrEF), and preserved (≥50% HFpEF) LVEF. Endpoints were the composite of cardiovascular death/HF hospitalization, and individual components.

Results: Median sUA was 6.72 (IQ:5.48-8.20) mg/dl in HFrEF, 6.41 (5.02-7.77) in HFmrEF, and 6.30 (5.20-7.70) in HFpEF. At a median 372-day follow-up, the composite endpoint occurred in 648 (13.1%) patients, with 176 (3.6%) deaths and 538 (10.9%) HF hospitalizations. Compared with lowest sUA quartile (Q), Q-III and Q-IV were significantly associated with the composite endpoint (adjusted HR 1.68: 95% CI 1.11-2.54; 2.46: 95% CI 1.66-3.64, respectively). By univariable analyses, HFrEF and HFmrEF patients in Q-III and Q-IV, and HFpEF patients in Q-IV, showed increased risk for the composite endpoint (P<0.05 for all); after model-adjustment, significant association of sUA with outcome persisted among HFrEF in Q-IV, and HFpEF in Q-III-IV.

Conclusions: In a large, contemporary-treated cohort of HF outpatients, sUA is an independent prognosticator of adverse outcome, which can be appreciated in HErEF and HFpEF patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejim.2021.04.001DOI Listing
April 2021

Urinary peptides in heart failure: a link to molecular pathophysiology.

Eur J Heart Fail 2021 Apr 21. Epub 2021 Apr 21.

Non-Profit Research Institution Alliance for the Promotion of Preventive Medicine, Mechelen, Belgium.

Aims: Heart failure (HF) is a major public health concern worldwide. The diversity of HF makes it challenging to decipher the underlying complex pathological processes using single biomarkers. We examined the association between urinary peptides and HF with reduced (HFrEF), mid-range (HFmrEF) and preserved (HFpEF) ejection fraction, defined based on the European Society of Cardiology guidelines, and the links between these peptide biomarkers and molecular pathophysiology.

Methods And Results: Analysable data from 5608 participants were available in the Human Urinary Proteome database. The urinary peptide profiles from participants diagnosed with HFrEF, HFmrEF, HFpEF and controls matched for sex, age, estimated glomerular filtration rate, systolic and diastolic blood pressure, diabetes and hypertension were compared applying the Mann-Whitney test, followed by correction for multiple testing. Unsupervised learning algorithms were applied to investigate groups of similar urinary profiles. A total of 577 urinary peptides significantly associated with HF were sequenced, 447 of which (77%) were collagen fragments. In silico analysis suggested that urinary biomarker abnormalities in HF principally reflect changes in collagen turnover and immune response, both associated with fibrosis. Unsupervised clustering separated study participants into two clusters, with 83% of non-HF controls allocated to cluster 1, while 65% of patients with HF were allocated to cluster 2 (P < 0.0001). No separation based on HF subtype was detectable.

Conclusions: Heart failure, irrespective of ejection fraction subtype, was associated with differences in abundance of urinary peptides reflecting collagen turnover and inflammation. These peptides should be studied as tools in early detection, prognostication, and prediction of therapeutic response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2195DOI Listing
April 2021

Impaired High-Density Lipoprotein Function in Patients With Heart Failure.

J Am Heart Assoc 2021 May 17;10(9):e019123. Epub 2021 Apr 17.

Department of Pediatrics University of Groningen Groningen The Netherlands.

Background We recently showed that, in patients with heart failure, lower high-density lipoprotein (HDL) cholesterol concentration was a strong predictor of death or hospitalization for heart failure. In a follow-up study, we suggested that this association could be partly explained by HDL proteome composition. However, whether the emerging concept of HDL function contributes to the prognosis of patients with heart failure has not been addressed. Methods and Results We measured 3 key protective HDL function metrics, namely, cholesterol efflux, antioxidative capacity, and anti-inflammatory capacity, at baseline and after 9 months in 446 randomly selected patients with heart failure from BIOSTAT-CHF (A Systems Biology Study to Tailored Treatment in Chronic Heart Failure). Additionally, the relationship between HDL functionality and HDL proteome composition was determined in 86 patients with heart failure. From baseline to 9 months, HDL cholesterol concentrations were unchanged, but HDL cholesterol efflux and anti-inflammatory capacity declined (both <0.001). In contrast, antioxidative capacity increased (<0.001). Higher HDL cholesterol efflux was associated with lower mortality after adjusting for BIOSTAT-CHF risk models and log HDL cholesterol (hazard ratio, 0.81; 95% CI, 0.71-0.92; =0.001). Other functionality measures were not associated with outcome. Several HDL proteins correlated with HDL functionality, mainly with cholesterol efflux. Apolipoprotein A1 emerged as the main protein associated with all 3 HDL functionality measures. Conclusions Better HDL cholesterol efflux at baseline was associated with lower mortality during follow-up, independent of HDL cholesterol. HDL cholesterol efflux and anti-inflammatory capacity declined during follow-up in patients with heart failure. Measures of HDL function may provide clinical information in addition to HDL cholesterol concentration in patients with heart failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.120.019123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200730PMC
May 2021

Global Differences in Burden and Treatment of Ischemic Heart Disease in Acute Heart Failure: REPORT-HF.

JACC Heart Fail 2021 May 7;9(5):349-359. Epub 2021 Apr 7.

University of Bergen, Stavanger University Hospital, Stavanger, Norway. Electronic address:

Objectives: The primary aim of the current study was to investigate global differences in prevalence, association with outcome, and treatment of ischemic heart disease (IHD) in patients with acute heart failure (AHF) in the REPORT-HF (International Registry to Assess Medical Practice With Longitudinal Observation for Treatment of Heart Failure) registry.

Background: Data on IHD in patients with AHF are primarily from Western Europe and North America. Little is known about global differences in treatment and prognosis of patients with IHD and AHF.

Methods: A total of 18,539 patients with AHF were prospectively enrolled from 44 countries and 365 centers in the REPORT-HF registry. Patients with a history of coronary artery disease, an ischemic event causing admission for AHF, or coronary revascularization were classified as IHD. Clinical characteristics, treatment, and outcomes of patients with and without IHD were explored.

Results: Compared with 8,766 (47%) patients without IHD, 9,773 (53%) patients with IHD were older, more likely to have a left ventricular ejection fraction <40% (heart failure with reduced ejection fraction [HFrEF]), and reported more comorbidities. IHD was more common in lower income compared with high-income countries (61% vs. 48%). Patients with IHD from countries with low health care expenditure per capita or without health insurance less likely underwent coronary revascularization or used anticoagulants at discharge. IHD was independently associated with worse cardiovascular death (hazard ratio: 1.21; 95% confidence interval: 1.09 to 1.35). The association between IHD and cardiovascular death was stronger in HFrEF compared with heart failure with preserved ejection fraction (p <0.001).

Conclusions: In this large global contemporary cohort of patients with AHF, IHD was more common in low-income countries and conveyed worse 1-year mortality, especially in HFrEF. Patients in regions with the greatest burden of IHD were less likely to receive coronary revascularization and treatment for IHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchf.2020.12.015DOI Listing
May 2021

Association of ventricular-arterial interaction with the response to cardiac resynchronization therapy.

Eur J Heart Fail 2021 Apr 9. Epub 2021 Apr 9.

2nd Cardiology Department, Attikon Hospital, University of Athens, Athens, Greece.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2186DOI Listing
April 2021

Telomere length is independently associated with all-cause mortality in chronic heart failure.

Heart 2021 Mar 31. Epub 2021 Mar 31.

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.

Objective: Patients with heart failure have shorter mean leucocyte telomere length (LTL), a marker of biological age, compared with healthy subjects, but it is unclear whether this is of prognostic significance. We therefore sought to determine whether LTL is associated with outcomes in patients with heart failure.

Methods: We measured LTL in patients with heart failure from the BIOSTAT-CHF Index (n=2260) and BIOSTAT-CHF Tayside (n=1413) cohorts. Cox proportional hazards analyses were performed individually in each cohort and the estimates combined using meta-analysis. Our co-primary endpoints were all-cause mortality and heart failure hospitalisation.

Results: In age-adjusted and sex-adjusted analyses, shorter LTL was associated with higher all-cause mortality in both cohorts individually and when combined (meta-analysis HR (per SD decrease in LTL)=1.16 (95% CI 1.08 to 1.24); p=2.66×10), an effect equivalent to that of being four years older. The association remained significant after adjustment for the BIOSTAT-CHF clinical risk score to account for known prognostic factors (HR=1.12 (95% CI 1.05 to 1.20); p=1.04×10). Shorter LTL was associated with both cardiovascular (HR=1.09 (95% CI 1.00 to 1.19); p=0.047) and non-cardiovascular deaths (HR=1.18 (95% CI 1.05 to 1.32); p=4.80×10). There was no association between LTL and heart failure hospitalisation (HR=0.99 (95% CI 0.92 to 1.07); p=0.855).

Conclusion: In patients with heart failure, shorter mean LTL is independently associated with all-cause mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/heartjnl-2020-318654DOI Listing
March 2021

Decongestion discriminates risk for one-year mortality in patients with improving renal function in acute heart failure.

Eur J Heart Fail 2021 Mar 31. Epub 2021 Mar 31.

School of Medicine, University College Dublin, Dublin, Ireland.

Aims: Improving renal function (IRF) is paradoxically associated with worse outcomes in acute heart failure (AHF), but outcomes may differ based on response to decongestion. We explored if the relationship of IRF with mortality in hospitalized AHF patients differs based on successful decongestion.

Methods And Results: We evaluated 760 AHF patients from AKINESIS for the relationship between IRF, change in B-type natriuretic peptide (BNP), and 1-year mortality. IRF was defined as a ≥20% increase in estimated glomerular filtration rate (eGFR) relative to admission. Adequate decongestion was defined as a ≥40% decrease in last measured BNP relative to admission. IRF occurred in 22% of patients who had a mean age of 69 years, 58% were men, 72% were white, and median admission eGFR was 49 mL/min/1.73 m . IRF patients had more severe heart failure reflected by lower admission eGFR, higher blood urea nitrogen, lower systolic blood pressure, lower sodium, and higher use of inotropes. IRF patients had higher 1-year mortality (25%) than non-IRF patients (15%) (P < 0.01). However, this relationship differed by BNP trajectory (P-interaction = 0.03). When stratified by BNP change, non-IRF patients and IRF patients with decreasing BNP had lower 1-year mortality than either non-IRF and IRF patients without decreasing BNP. However, in multivariate analysis, IRF was not associated with mortality [adjusted hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.7-1.5] while BNP was (adjusted HR 0.5, 95% CI 0.3-0.7). When IRF was evaluated as transiently occurring or persisting at discharge, again only BNP change was significantly associated with mortality.

Conclusion: Improving renal function is associated with mortality in AHF but not independent of other variables and congestion status. Achieving adequate decongestion, as reflected by lower BNP, in AHF is more strongly associated with mortality than IRF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2179DOI Listing
March 2021

Non-adherence to heart failure medications predicts clinical outcomes: assessment in a single spot urine sample by liquid chromatography-tandem mass spectrometry (results of a prospective multicentre study).

Eur J Heart Fail 2021 Mar 23. Epub 2021 Mar 23.

Department of Cardiovascular Science, University of Leicester, NIHR Leicester Biomedical Research Centre, Cardiovascular Unit and University Hospitals of Leicester NHS Trust, Leicester, UK.

Aims: Liquid chromatography-mass spectrometry (LC-MS/MS) is an objective new technique to assess non-adherence to medications. We used this method to study the prevalence, predictors and outcomes of non-adherence in patients with heart failure with reduced left ventricular ejection fraction (HFrEF).

Methods And Results: This study included 1296 patients with HFrEF from BIOSTAT-CHF, a study that aimed to optimise guideline-recommended therapies. Angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists, β-blockers and loop diuretics were measured in a single spot urine sample at 9 months using LC-MS/MS. The relationship between medication non-adherence and the composite endpoint of all-cause death or heart failure hospitalisation, over a median follow-up of 21 months, was evaluated. Non-adherence to at least one prescribed medication was observed in 45.9% of patients. The strongest predictor of non-adherence was non-adherence to any of the other medication classes (P < 0.0005). Regional differences within Europe were observed. On multivariable analyses, non-adherence to ACEi/ARBs and β-blockers was associated with an increased risk of the composite endpoint [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.09-1.95, P = 0.008 and HR 1.48, 95% CI 1.12-1.96, P = 0.006, respectively). Non-adherence to β-blockers was also associated with an increased risk of death (HR 2.48, 95% CI 1.67-3.68, P < 0.0005). Patients who were non-adherent to loop diuretics were healthier and had a decreased risk of the composite endpoint (HR 0.69, 95% CI 0.51-0.93, P = 0.014). Non-adherence to mineralocorticoid receptor antagonists was not related to any clinical outcome.

Conclusion: Non-adherence to medications, assessed by a single urine test, is common and predicts clinical outcomes in patients with HFrEF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2160DOI Listing
March 2021

Dipeptidyl peptidase 3, a marker of the antagonist pathway of the renin-angiotensin-aldosterone system in patients with heart failure.

Eur J Heart Fail 2021 Mar 20. Epub 2021 Mar 20.

University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Aims: Recently, dipeptidyl peptidase 3 (DPP3) has been discovered as the peptidase responsible for cleavage of angiotensin (1-7) [Ang (1-7)]. Ang (1-7) is part of the angiotensin-converting enzyme-Ang (1-7)-Mas pathway which is considered to antagonize the renin-angiotensin-aldosterone system (RAAS). Since DPP3 inhibits the counteracting pathway of the RAAS, we hypothesize that DPP3 might be deleterious in the setting of heart failure. However, no data are available on DPP3 in chronic heart failure. We therefore investigated the clinical characteristics and outcome related to elevated DPP3 concentrations in patients with worsening heart failure.

Methods And Results: Dipeptidyl peptidase 3 was measured in 2156 serum samples of patients with worsening heart failure using luminometric immunoassay (DPP3-LIA) by 4TEEN4 Pharmaceuticals GmbH, Hennigsdorf, Germany. Predictors of DPP3 levels were selected using multiple linear regression with stepwise backward selection. Median DPP3 concentration was 11.45 ng/mL with a range from 2.8 to 84.9 ng/mL. Patients with higher DPP3 concentrations had higher renin [78.3 (interquartile range, IQR 26.3-227.7) vs. 120.7 IU/mL (IQR 34.74-338.9), P < 0.001, for Q1-3 vs. Q4] and aldosterone [88 (IQR 44-179) vs. 116 IU/mL (IQR 46-241), P < 0.001, for Q1-3 vs. Q4] concentrations. The strongest independent predictors for higher concentration of DPP3 were log-alanine aminotransferase, log-total bilirubin, the absence of diabetes, higher osteopontin, fibroblast growth factor-23 and N-terminal pro-B-type natriuretic peptide concentrations (all P < 0.001). In univariable survival analysis, DPP3 was associated with mortality and the combined endpoint of death or heart failure hospitalization (P < 0.001 for both). After adjustment for confounders, this association was no longer significant.

Conclusions: In patients with worsening heart failure, DPP3 is a marker of more severe disease with higher RAAS activity. It may be deleterious in heart failure by counteracting the Mas receptor pathway. Procizumab, a specific antibody against DPP3, might be a potential future treatment option for patients with heart failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2158DOI Listing
March 2021

The value of spot urinary creatinine as a marker of muscle wasting in patients with new-onset or worsening heart failure.

J Cachexia Sarcopenia Muscle 2021 Jun 20;12(3):555-567. Epub 2021 Mar 20.

Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Background: Muscle wasting and unintentional weight loss (cachexia) have been associated with worse outcomes in heart failure (HF), but timely identification of these adverse phenomena is difficult. Spot urinary creatinine may be an easily accessible marker to assess muscle loss and cachexia. This study investigated the association of urinary creatinine with body composition changes and outcomes in patients with new-onset or worsening HF (WHF).

Methods: In BIOSTAT-CHF, baseline spot urinary creatinine measurements were available in 2315 patients with new-onset or WHF in an international cohort (index cohort) and a validation cohort of 1431 similar patients from Scotland.

Results: Median spot urinary creatinine concentrations were 5.2 [2.7-9.6] mmol/L in the index cohort. Median age was 69 ± 12 years and 73% were men. Lower spot urinary creatinine was associated with older age, lower height and weight, worse renal function, more severe HF, and a higher risk of >5% weight loss from baseline to 9 months (odds ratio = 1.23, 95% CI = 1.09-1.39 per log decrease; P = 0.001). Spot urinary creatinine was associated with Evans criteria of cachexia (OR = 1.26 per log decrease, 95% CI = 1.04-1.49; P = 0.016) and clustered with markers of heart failure severity in hierarchical cluster analyses. Lower urinary creatinine was associated with poorer exercise capacity and quality of life (both P < 0.001) and predicted a higher rate for all-cause mortality [hazard ratio (HR) = 1.27, 95% CI = 1.17-1.38 per log decrease; P < 0.001] and the combined endpoints HF hospitalization or all-cause mortality (HR = 1.23, 95% CI = 1.15-1.31 per log decrease; P < 0.001). Significance was lost after addition of the BIOSTAT risk model. Analyses of the validation cohort yielded similar findings.

Conclusions: Lower spot urinary creatinine is associated with smaller body dimensions, renal dysfunction, and more severe HF in patients with new-onset/WHF. Additionally, lower spot urinary creatinine is associated with an increased risk of weight loss and a poorer exercise capacity/quality of life. Urinary creatinine could therefore be a novel, easily obtainable marker to assess (risk of) muscle wasting in HF patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcsm.12690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200450PMC
June 2021

Interplay of Mineralocorticoid Receptor Antagonists and Empagliflozin in Heart Failure: EMPEROR-Reduced.

J Am Coll Cardiol 2021 Mar;77(11):1397-1407

Baylor University Medical Center, Dallas, Texas, USA; Imperial College, London, United Kingdom.

Background: Mineralocorticoid receptor antagonists (MRAs) and sodium glucose co-transporter 2 inhibitors favorably influence the clinical course of patients with heart failure and reduced ejection fraction.

Objectives: This study sought to study the mutual influence of empagliflozin and MRAs in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction).

Methods: Secondary analysis that compared the effects of empagliflozin versus placebo in 3,730 patients with heart failure and a reduced ejection fraction, of whom 71% used MRAs at randomization.

Results: The effects of empagliflozin on the primary endpoint, on most efficacy endpoints, and on safety were similar in patients receiving or not receiving an MRA (interaction p > 0.20). For cardiovascular death, the hazard ratios for the effect of empagliflozin versus placebo were 0.82 (95% confidence interval [CI]: 0.65 to 1.05) in MRA users and 1.19 (95% CI: 0.82 to 1.71) in MRA nonusers (interaction p = 0.10); a similar pattern was seen for all-cause mortality (interaction p = 0.098). Among MRA nonusers at baseline, patients in the empagliflozin group were 35% less likely than those in the placebo group to initiate treatment with an MRA following randomization (hazard ratio: 0.65; 95% CI: 0.49 to 0.85). Among MRA users at baseline, patients in the empagliflozin group were 22% less likely than those in the placebo group to discontinue treatment with an MRA following randomization (hazard ratio: 0.78; 95% CI: 0.64 to 0.96). Severe hyperkalemia was less common in the empagliflozin group.

Conclusions: In EMPEROR-Reduced, the use of MRAs did not influence the effect of empagliflozin to reduce adverse heart failure and renal outcomes. Treatment with empagliflozin was associated with less discontinuation of MRAs. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2021.01.044DOI Listing
March 2021

Empagliflozin in Patients With Heart Failure, Reduced Ejection Fraction, and Volume Overload: EMPEROR-Reduced Trial.

J Am Coll Cardiol 2021 Mar;77(11):1381-1392

Investigation Network Initiative-Cardiovascular and Renal Clinical Trialists, University Hospital, University of Lorraine, Nancy, France.

Background: Investigators have hypothesized that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert diuretic effects that contribute to their ability to reduce serious heart failure events, and this action is particularly important in patients with fluid retention.

Objectives: This study sought to evaluate the effects of the SGLT2 inhibitor empagliflozin on symptoms, health status, and major heart failure outcomes in patients with and without recent volume overload.

Methods: This double-blind randomized trial compared the effects of empagliflozin and placebo in 3,730 patients with heart failure and a reduced ejection fraction, with or without diabetes. Approximately 40% of the patients had volume overload in the 4 weeks before study enrollment.

Results: Patients with recent volume overload were more likely to have been hospitalized for heart failure and to have received an intravenous diuretic agent in an outpatient setting in the previous 12 months, and to experience a heart failure event following randomization, even though they were more likely to be treated with high doses of a loop diuretic agent as an outpatient (all p < 0.001). When compared with placebo, empagliflozin reduced the composite risk of cardiovascular death or hospitalization for heart failure, decreased total hospitalizations for heart failure, and improved health status and functional class. Yet despite the predisposition of patients with recent volume overload to fluid retention, the magnitude of these benefits (even after 1 month of treatment) was not more marked in patients with recent volume overload (interaction p values > 0.05). Changes in body weight, hematocrit, and natriuretic peptides (each potentially indicative of a diuretic action of SGLT2 inhibitors) did not track each other closely in their time course or in individual patients.

Conclusions: Taken together, study findings do not support a dominant role of diuresis in mediating the physiological changes or clinical benefits of SGLT2 inhibitors on the course of heart failure in patients with a reduced ejection fraction. (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2021.01.033DOI Listing
March 2021

The management of secondary mitral regurgitation in patients with heart failure: a joint position statement from the Heart Failure Association (HFA), European Association of Cardiovascular Imaging (EACVI), European Heart Rhythm Association (EHRA), and European Association of Percutaneous Cardiovascular Interventions (EAPCI) of the ESC.

Eur Heart J 2021 Mar 18. Epub 2021 Mar 18.

Department of Cardiology, Inselspital, University of Bern, Bern, Switzerland.

Secondary (or functional) mitral regurgitation (SMR) occurs frequently in chronic heart failure (HF) with reduced left ventricular (LV) ejection fraction, resulting from LV remodelling that prevents coaptation of the valve leaflets. Secondary mitral regurgitation contributes to progression of the symptoms and signs of HF and confers worse prognosis. The management of HF patients with SMR is complex and requires timely referral to a multidisciplinary Heart Team. Optimization of pharmacological and device therapy according to guideline recommendations is crucial. Further management requires careful clinical and imaging assessment, addressing the anatomical and functional features of the mitral valve and left ventricle, overall HF status, and relevant comorbidities. Evidence concerning surgical correction of SMR is sparse and it is doubtful whether this approach improves prognosis. Transcatheter repair has emerged as a promising alternative, but the conflicting results of current randomized trials require careful interpretation. This collaborative position statement, developed by four key associations of the European Society of Cardiology-the Heart Failure Association (HFA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), European Association of Cardiovascular Imaging (EACVI), and European Heart Rhythm Association (EHRA)-presents an updated practical approach to the evaluation and management of patients with HF and SMR based upon a Heart Team approach.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/eurheartj/ehab086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014526PMC
March 2021

Finerenone and Chronic Kidney Disease Outcomes in Type 2 Diabetes. Reply.

N Engl J Med 2021 03;384(11):e42

National and Kapodistrian University of Athens, Athens Greece.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1056/NEJMc2036175DOI Listing
March 2021

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

J Card Fail 2021 Mar 1. Epub 2021 Mar 1.

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

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cardfail.2021.01.022DOI Listing
March 2021

Machine learning based on biomarker profiles identifies distinct subgroups of heart failure with preserved ejection fraction.

Eur J Heart Fail 2021 Mar 2. Epub 2021 Mar 2.

Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.

Aims: The lack of effective therapies for patients with heart failure with preserved ejection fraction (HFpEF) is often ascribed to the heterogeneity of patients with HFpEF. We aimed to identify distinct pathophysiologic clusters of HFpEF based on circulating biomarkers.

Methods And Results: We performed an unsupervised cluster analysis using 363 biomarkers from 429 patients with HFpEF. Relative differences in expression profiles of the biomarkers between clusters were assessed and used for pathway over-representation analyses. We identified four distinct patient subgroups based on their biomarker profiles: cluster 1 with the highest prevalence of diabetes mellitus and renal disease; cluster 2 with oldest age and frequent age-related comorbidities; cluster 3 with youngest age, largest body size, least symptoms and lowest N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels; and cluster 4 with highest prevalence of ischaemic aetiology, smoking and chronic lung disease, most symptoms, as well as highest NT-proBNP and troponin levels. Over a median follow-up of 21 months, the occurrence of death or heart failure hospitalization was highest in clusters 1 and 4 (62.1% and 62.8%, respectively) and lowest in cluster 3 (25.6%). Pathway over-representation analyses revealed that the biomarker profile of patients in cluster 1 was associated with activation of inflammatory pathways while the biomarker profile of patients in cluster 4 was specifically associated with pathways implicated in cell proliferation regulation and cell survival.

Conclusion: Unsupervised cluster analysis based on biomarker profiles identified mutually exclusive subgroups of patients with HFpEF with distinct biomarker profiles, clinical characteristics and outcomes, suggesting different underlying pathophysiological pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2144DOI Listing
March 2021

Relation of Decongestion and Time to Diuretics to Biomarker Changes and Outcomes in Acute Heart Failure.

Am J Cardiol 2021 05 20;147:70-79. Epub 2021 Feb 20.

Department of Medicine, School of Medicine, University College Dublin, Dublin, Ireland. Electronic address:

Prompt treatment may mitigate the adverse effects of congestion in the early phase of heart failure (HF) hospitalization, which may lead to improved outcomes. We analyzed 814 acute HF patients for the relationships between time to first intravenous loop diuretics, changes in biomarkers of congestion and multiorgan dysfunction, and 1-year composite end point of death or HF hospitalization. B-type natriuretic peptide (BNP), high sensitivity cardiac troponin I (hscTnI), urine and serum neutrophil gelatinase-associated lipocalin, and galectin 3 were measured at hospital admission, hospital day 1, 2, 3 and discharge. Time to diuretics was not correlated with the timing of decongestion defined as BNP decrease ≥ 30% compared with admission. Earlier BNP decreases but not time to diuretics were associated with earlier and greater decreases in hscTnI and urine neutrophil gelatinase-associated lipocalin, and lower incidence of the composite end point. After adjustment for confounders, only no BNP decrease at discharge was significantly associated with mortality but not the composite end point (p = 0.006 and p = 0.062, respectively). In conclusion, earlier time to decongestion but not the time to diuretics was associated with better biomarker trajectories. Residual congestion at discharge rather than the timing of decongestion predicted a worse prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjcard.2021.01.040DOI Listing
May 2021

Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association.

Eur J Heart Fail 2021 Mar 3;23(3):352-380. Epub 2021 Mar 3.

In this document, we propose a universal definition of heart failure (HF) as a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. We also propose revised stages of HF as: At risk for HF (Stage A), Pre-HF (Stage B), Symptomatic HF (Stage C) and Advanced HF (Stage D). Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). This includes HF with reduced ejection fraction (HFrEF): symptomatic HF with LVEF ≤40%; HF with mildly reduced ejection fraction (HFmrEF): symptomatic HF with LVEF 41-49%; HF with preserved ejection fraction (HFpEF): symptomatic HF with LVEF ≥50%; and HF with improved ejection fraction (HFimpEF): symptomatic HF with a baseline LVEF ≤40%, a ≥10 point increase from baseline LVEF, and a second measurement of LVEF > 40%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ejhf.2115DOI Listing
March 2021

Efficacy and safety of SGLT2 inhibitors in heart failure: systematic review and meta-analysis.

ESC Heart Fail 2020 12;7(6):3298-3309

Department of Cardiology (CVK) and Berlin Institute of Health Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK), partner site Berlin, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, D-13353, Berlin, Germany.

Aims: We sought to conduct a meta-analysis regarding the safety and efficacy of sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with heart failure (HF).

Methods And Results: MEDLINE, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov were searched from their inception to November 2020 for placebo-controlled randomized controlled trials of SGLT2 inhibitors. Randomized controlled trials were selected if they reported at least one of the prespecified outcomes in patients with HF. Hazard ratios (HRs) or risk ratios and their corresponding 95% confidence intervals were pooled using a random-effects model. A total of seven trials including 16 820 HF patients (N = 8884 in the SGLT2 inhibitor arms; N = 7936 in the placebo arms) were included. In the overall HF cohort, SGLT2 inhibitors compared with placebo significantly reduced the risk of the composite endpoint of first HF hospitalization or cardiovascular death [HR: 0.77 (0.72-0.83); P < 0.001; I = 0%], time to first HF hospitalization [HR: 0.71 (0.64-0.78); P < 0.001; I = 0], cardiovascular mortality [HR: 0.87 (0.79-0.96); P = 0.005; I = 0%], and all-cause mortality [HR: 0.89 (0.82-0.96); P = 0.004; I = 0%]. Results remained consistent across HF-specific trials and according to diabetes mellitus status. A trend towards benefit was observed in patients with HF with preserved ejection fraction for the composite of HF hospitalization and cardiovascular death [HR: 0.80 (0.63-1.00); P = 0.05; I = 29%]. No increased risk of hypovolaemia, hyperkalaemia, and hypotension was seen with SGLT2 inhibitors compared with placebo.

Conclusions: SGLT2 inhibitors significantly improve cardiovascular outcomes including cardiovascular and all-cause mortality in patients with HF without an increased risk of serious adverse events. A trend towards benefit was observed in patients with HF with preserved ejection fraction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ehf2.13169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755023PMC
December 2020

Patient factors associated with titration of medical therapy in patients with heart failure with reduced ejection fraction: data from the QUALIFY international registry.

ESC Heart Fail 2021 Apr 10;8(2):861-871. Epub 2021 Feb 10.

Department of Cardiology, Saint Joseph Hospital, Paris, France.

Aims: Failure to prescribe key medicines at evidence-based doses is associated with increased mortality and hospitalization for patients with Heart Failure with reduced Ejection Fraction (HFrEF). We assessed titration patterns of guideline-recommended HFrEF medicines internationally and explored associations with patient characteristics in the global, prospective, observational, longitudinal registry.

Methods And Results: Data were collected from September 2013 through December 2014, with 7095 patients from 36 countries [>18 years, previous HF hospitalization within 1-15 months, left ventricular ejection fraction (LVEF) ≤ 40%] enrolled, with dosage data at baseline and up to 18 months from 4368 patients. In 4368 patients (mean age 63 ± 17 years, 75% male) ≥ 100% target doses at baseline: 30.6% (ACEIs), 2.9% (ARBs), 13.9% (BBs), 53.8% (MRAs), 26.2% (ivabradine). At final follow-up, ≥100% target doses achieved in more patients for ACEI (34.8%), BB (18.0%), and ivabradine (30.5%) but unchanged for ARBs (3.2%) and MRAs (53.7%). Adjusting for baseline dosage, uptitration during follow-up was more likely with younger age, higher systolic blood pressure, and in absence of chronic kidney disease or diabetes for ACEIs/ARBs; younger age, higher body mass index, higher heart rate, lower LVEF, and absence of coronary artery disease for BBs. For ivabradine, uptitration was more likely with higher resting heart rate.

Conclusions: The international QUALIFY Registry suggests that few patients with HFrEF achieve target doses of disease-modifying medication, especially older patients and those with co-morbidity. Quality improvement initiatives are urgently required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ehf2.13237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006614PMC
April 2021