Events In Heart Failure Patients Research Articles

Baseline characteristics of patients with heart failure with mildly reduced or preserved ejection fraction: The FINEARTS-HF trial.

To describe the baseline characteristics of participants in the FINEARTS-HF trial, contextualized with prior trials including patients with heart failure (HF) with mildly reduced and preserved ejection fraction (HFmrEF/HFpEF). The FINEARTS-HF trial is comparing the effects of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo in reducing cardiovascular death and total worsening HF events in patients with HFmrEF/HFpEF. Patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≥40%, estimated glomerular filtration rate ≥ 25 ml/min/1.73 m2, elevated natriuretic peptide levels and evidence of structural heart disease were enrolled and randomized to finerenone titrated to a maximum of 40 mg once daily or matching placebo. We validly randomized 6001 patients to finerenone or placebo (mean age 72 ± 10 years, 46% women). The majority were New York Heart Association functional class II (69%). The baseline mean LVEF was 53 ± 8% (range 34-84%); 36% of participants had a LVEF <50% and 64% had a LVEF ≥50%. The median N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 1041 (interquartile range 449-1946) pg/ml. A total of 1219 (20%) patients were enrolled during or within 7 days of a worsening HF event, and 3247 (54%) patients were enrolled within 3 months of a worsening HF event. Compared with prior large-scale HFmrEF/HFpEF trials, FINEARTS-HF participants were more likely to have recent (within 6 months) HF hospitalization and greater symptoms and functional limitations. Further, concomitant medications included a larger percentage of sodium-glucose cotransporter 2 inhibitors and angiotensin receptor-neprilysin inhibitors than previous trials. FINEARTS-HF has enrolled a broad range of high-risk patients with HFmrEF and HFpEF. The trial will determine the safety and efficacy of finerenone in this population.

Early Initiation of SGLT2 Inhibitor is Important Irrespective of Ejection Fraction

Introduction Sodium Glucose Cotransporter inhibitor (SGLTi) has revolutionized the medical management of heart failure in the last decade. This molecule was initially described as a glucose-lowering agent but now it has been recommended in patients with chronic heart failure irrespective of ejection fraction and diabetic status. SGLT2 inhibitor reduces preload by natriuresis and diuresis, reduces afterload, decreases pulmonary artery pressure, improves myocardial energetics, and decreases myocardial fibrosis. It also reduces NTpro BNP levels in heart failure patients, decreases serum uric acid, and promotes weight loss. It has also been proposed that this molecule has a favorable effect on vascular remodeling. SGLT-2i improves cardiac output and attenuates maladaptive cardiac remodeling, chronic inflammation, oxidative stress, and endothelial dysfunction (ED) by restoring the activity of nitric oxide (NO) within the vascular endothelium. As was foreseeable this molecule became one of the foundation pillars in the management of heart failure with reduced as well as preserved ejection fraction. SGLT2i also has a reno-protective effect, particularly in patients with heart failure and diabetes. Evidence with SGLT2 inhibitor in Heart failure with preserved ejection fraction (HFpEF) DELIVER TRIAL has evaluated the effect of dapagliflozin on total (first and recurrent) heart failure events in patients with heart failure having preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF). A total of 6263 patients with LVEF of more than 40 %, NHYA Class II-IV, and high NT-pro BNP (&gt;300pg/ml in sinus rhythm and &gt; 600pg/ml in patients with atrial fibrillation) were included over the total study period of two years. Dapagliflozin 10 mg was compared to placebo. In patients with HFmrEF and HFpEF, dapagliflozin reduced the risk of total heart failure events and heart failurerelated hospital admissions. (1)

Predictive Value of 5-Methoxytryptophan on Long-Term Clinical Outcome after PCI in Patients with Acute Myocardial Infarction-a Prospective Cohort Study.

In recent years, 5-Methoxytryptophan (5-MTP) has been identified as an endothelial factor with vaso-protective and anti-inflammatory properties. In this prospective cohort study, a total of 407 patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) successfully were enrolled. A 1-year follow-up Kaplan-Meier survival analysis was used for evaluating the correlation between 5-MTP and major adverse cardiovascular event (MACE) while Cox proportional-hazards regression was used to identify predictive values of 5-MTP on MACE after AMI. Increased 5-MTP level led to a significant downtrend in the incidence of MACE (All Log-rank p < 0.05). Thus, a high baseline 5-MTP could reduce the 1-year incidence of MACE (HR = 0.33, 95%Cl 0.17-0.64, p = 0.001) and heart failure (HF) (HR = 0.28, 95% Cl 0.13-0.62, p = 0.002). Subgroup analysis indicated the predictive value of 5-MTP was more significant in patients aged ≤ 65years and those with higher baseline NT-proBNP, T2DM, STEMI, and baseline HF with preserved LVEF (HFpEF) characteristics. Plasma 5-MTP is an independent and protective early biomarker for 1-year MACE and HF events in patients with AMI, especially in younger patients and those with T2DM, STEMI, and baseline HFpEF characteristics.

Comparison of Incidence and Prognostic Impact of Ischemic Major Bleeding and Heart Failure Events in Patients With Chronic Coronary Syndrome: Insights From the CORONOR Registry.

Evaluation of the residual risk in patient with chronic coronary syndrome is challenging in daily practice. Several types of events (myocardial infarction, ischemic stroke, bleeding, and heart failure [HF]) may occur, and their impact on subsequent mortality is unclear in the era of modern evidence-based pharmacotherapy. CORONOR (Suivi d'une cohorte de patients Coronariens stables en région Nord-pas-de-Calais) is a prospective multicenter cohort that enrolled 4184 consecutive unselected outpatients with chronic coronary syndrome. We analyzed the incidence, correlates, and impact of ischemic events (a composite of myocardial infarction and ischemic stroke), major bleeding (Bleeding Academic Research Consortium 3 or higher), and hospitalization for HF on subsequent patient mortality. During follow-up (median, 4.9 years), 677 patients (16.5%) died. The 5-year cumulative incidences (death as competing event) of ischemic events, major bleeding, and HF hospitalization were 6.3% (5.6%-7.1%), 3.1% (2.5%-3.6%), and 8.1% (7.3%-9%), respectively. Ischemic events, major bleeding, and HF hospitalization were each associated with all-cause mortality. Major bleeding and hospitalization for HF were associated with the highest mortality rates in the postevent period (42.4%/y and 34.7%/y, respectively) compared with incident ischemic events (13.1%/y). The age- and sex-adjusted hazard ratios for all-cause mortality were 3.57 (95% CI, 2.77-4.61), 9.88 (95% CI, 7.55-12.93), and 8.60 (95% CI, 7.15-10.35) for ischemic events, major bleeding, and hospitalization for HF, respectively (all P<0.001). Hospitalization for HF has become both the most frequent and one of the most ominous events among patients with chronic coronary syndrome. Although less frequent, major bleeding is strongly associated with worse patient survival. Secondary prevention should not be limited to preventing ischemic events. Minimizing bleeding and preventing HF may be at least as important.

Atrial Fibrillation Ablation in Heart Failure With Reduced vs Preserved Ejection Fraction

Catheter ablation is associated with reduced heart failure (HF) hospitalization and death in select patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). However, the benefit in patients with HF with preserved ejection fraction (HFpEF) is uncertain. To investigate whether catheter ablation for AF is associated with reduced HF-related outcomes according to HF phenotype. A systematic search of MEDLINE, Embase, and Cochrane Central was conducted among studies published from inception to September 2023. Parallel-group randomized clinical trials (RCTs) comparing catheter ablation with conventional rate or rhythm control therapies in patients with HF, New York Heart Association functional class II or greater, and a history of paroxysmal or persistent AF were included. Pairs of independent reviewers screened 7531 titles and abstracts, of which 12 RCTs and 4 substudies met selection criteria. Data were abstracted in duplicate according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Pooled effect estimates were calculated using random-effects Mantel-Haenszel models. Interaction P values were used to test for subgroup differences. The primary outcome was HF events, defined as HF hospitalization, clinically significant worsening of HF, or unscheduled visits to a clinician for treatment intensification. Secondary outcomes included cardiovascular and all-cause mortality. A total of 12 RCTs with 2465 participants (mean [SD] age, 65.3 [9.7] years; 658 females [26.7%]) were included; there were 1552 participants with HFrEF and 913 participants with HFpEF. Compared with conventional rate or rhythm control, catheter ablation was associated with reduced risk of HF events in HFrEF (risk ratio [RR], 0.59; 95% CI, 0.48-0.72), while there was no benefit in patients with HFpEF (RR, 0.93; 95% CI, 0.65-1.32) (P for interaction = .03). Catheter ablation was associated with reduced risk of cardiovascular death compared with conventional therapies in HFrEF (RR, 0.49; 95% CI, 0.34-0.70) but a differential association was not detected in HFpEF (RR, 0.91; 95% CI, 0.46-1.79) (P for interaction = .12). Similarly, no difference in the association of catheter ablation with all-cause mortality was found between HFrEF (RR vs conventional therapies, 0.63; 95% CI, 0.47-0.86) and HFpEF (RR vs conventional therapies, 0.95; 95% CI, 0.39-2.30) groups (P for interaction = .39). This study found that catheter ablation for AF was associated with reduced risk of HF events in patients with HFrEF but had limited or no benefit in HFpEF. Results from ongoing trials may further elucidate the role of catheter ablation for AF in HFpEF.

Outcomes in patients treated with loop diuretics without a diagnosis of heart failure: a retrospective cohort study.

Loop diuretics are commonly prescribed in the community, not always to patients with a recorded diagnosis of heart failure (HF). The rate of HF events in patients prescribed loop diuretics without a diagnosis of HF is unknown. This was a propensity-matched cohort study using data from the Clinical Practice Research Datalink, Hospital Episode Statistics and Office of National Statistics in the UK. Patients prescribed a loop diuretic without a diagnosis of HF (loop diuretic group) between 1 January 2010 and 31 December 2015 were compared with patients with HF (HF group)-analysis A, and patients with risk factors for HF (either ischaemic heart disease, or diabetes and hypertension-at-risk group)-analysis B. The primary endpoint was an HF event (a composite of presentation with HF symptoms, HF hospitalisation, HF diagnosis (analysis B only) and all-cause mortality). From a total population of 180 384 patients (78 968 in the loop diuretic group, 28 177 in the HF group and 73 239 in the at-risk group), there were 59 694 patients, 22 352 patients and 57 219 patients in the loop diuretic, HF and at-risk groups, respectively, after exclusion criteria were applied. After propensity matching for age, sex and comorbidities, patients in the loop diuretic group had a similar rate of HF events as those in the HF group (71.9% vs 72.1%; HR=0.92 (95% CI 0.90 to 0.94); p<0.001), and twice as those in the at-risk group (59.2% vs 35.7%; HR=2.04 (95% CI 2.00 to 2.08); p<0.001). Patients prescribed a loop diuretic without a recorded diagnosis of HF experience HF events at a rate comparable with that of patients with a recorded diagnosis of HF; many of these patients may have undiagnosed HF.

Incremental value of diastolic wall strain in predicting heart failure events in patients with atrial fibrillation.

Diastolic wall strain (DWS), an echocardiographic index based on linear elasticity theory, has been identified as a predictor of heart failure (HF) in patients with sinus rhythm. However, its effectiveness in atrial fibrillation (AF) patients remains uncertain. This study aims to assess DWS as a predictor of HF in AF patients with preserved ejection fraction. We analysed a prospective database of AF patients undergoing transthoracic echocardiography. AF patients with reduced left ventricular ejection fraction (< 50%), posterior wall motion abnormality, hypertrophic cardiomyopathy, valvular heart disease, pericardial disease, congenital heart disease, or history of pacemaker/implantable cardioverter-defibrillator implantation or cardiac surgery were excluded. The study followed patients until HF development, death, or last visit. Follow-up for patients who underwent catheter ablation was censored on the date of their procedure. HF was ascertained based on the Framingham criteria. DWS was calculated using a validated formula: DWS = (PWs -PWd)/PWs, where PWs is the posterior wall thickness at end-systole and PWd is the posterior wall thickness at end-diastole. Among 411 study patients (mean age 69.6 years, 66% men), 20 (5%) was underwent catheter ablation and 57 (14%) developed HF during a mean follow-up of 82 months. Cox-proportional hazards demonstrated that low DWS (≤ 0.33) significantly predicted HF events (hazard ratio [HR] 3.28, 95% confidence interval [CI]) 1.81-5.94, P < 0.0001), independent of age (per 10 years; HR 1.99, 95% CI 1.35-2.93, P < 0.001), indexed left ventricular mass (per 10g/m2; HR 1.16, 95% CI 1.05-1.27, P < 0.01), and indexed left atrial volume (per 10 mL/m2; HR 1.14, 95% CI 1.04-1.24, P < 0.01). Additionally, global log-likelihood ratio chi-square statistics indicated that DWS incrementally predicts HF development beyond age, indexed left ventricular mass, and left atrial volume (P < 0.001).

Impact of guideline-directed medical therapy on systolic blood pressure and cardiovascular outcomes in patients with heart failure and low blood pressure: A systematic review and meta-analysis.

Existing research indicates that patients with heart failure (HF) may have restricted access to guideline-directed medical therapy (GDMT) when their blood pressure (BP) is comparatively low. However, recent clinical trials suggest that HF patients with low BP could still benefit from certain HF medications, which have a minimal impact on BP. This systematic review and meta-analysis was conducted to determine whether this applies to all GDMT. A systematic search of MEDLINE and EMBASE was conducted for studies published from inception to 10 January 2024. Randomized controlled trials were selected if they reported on the longitudinal change of systolic BP (SBP) due to GDMT, or the risks of cardiovascular events in HF patients based on SBP categories. Weighted mean difference (WMD), hazard ratio or relative risk, and corresponding 95% confidence intervals (CI) were pooled for meta-analysis where possible. Data from 20 studies, encompassing information on 84 782 individuals, were analysed. Overall, GDMT is associated with lower SBP (WMD, -2.16; 95% CI -2.86 to -1.46), with no significant difference between baseline low and non-low BP subgroups (interaction p = 0.810). However, SBP of the treatment group increased by 5.8 mmHg from baseline in the low SBP subgroup during follow-up, while it decreased by 4.0 mmHg in the baseline non-low SBP subgroup. GDMT demonstrated similar cardiovascular benefits and risk of hypotension between low and non-low SBP subgroups (interaction p = 0.318 and 0.903, respectively). Guideline-directed medical therapy is associated with a negligible decrease in SBP, but can provide similar cardiovascular benefits in both low and non-low SBP HF patients, with no significant interaction with SBP as to hypotension. Therefore, GDMT should be initiated and maintained in HF patients with low BP.

Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights from the EMPACT-MI Trial.

Empagliflozin reduces the risk of heart failure events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, and in those with prevalent heart failure irrespective of ejection fraction. While EMPACT-MI showed empagliflozin does not reduce the risk of the composite of hospitalization of heart failure and all-cause mortality, the impact of empagliflozin on first and recurrent heart failure events in patients after myocardial infarction is unknown. EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for heart failure based on newly developed left ventricular ejection fraction of <45% and/or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for heart failure outcomes. Over a median of follow-up of 17.9 months, the risk for first heart failure hospitalization and total heart failure hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 (3.6%) vs. 153 (4.7%) patients with events, HR 0.77 [95% CI 0.60, 0.98], P=0.031 for first heart failure hospitalization and 148 vs. 207 events, RR 0.67 [95% CI 0.51, 0.89], P=0.006 for total heart failure hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total heart failure hospitalizations. Post-discharge need for new use of diuretics, renin-angiotensin modulators, and mineralocorticoid receptor antagonists were less in patients randomized to empagliflozin than placebo (all p<0.05). In patients after acute myocardial infarction with left ventricular dysfunction or congestion, empagliflozin reduced the risk of heart failure.

Temporal association of ventricular arrhythmias and respiratory events in heart failure patients with central sleep apnoea

In contrast to obstructive sleep apnoea, the peak of sympathetic tone in central sleep apnoea occurs during the hyperventilation phase. To explore the temporal association of premature ventricular complex (PVC) burden in the context of the apnoea/hypopnoea-hyperpnoea cycle, the duration of apnoea/hypopnoea was defined as 100 %. We assessed the PVC burden throughout the apnoea/hypopnoea-hyperpnoea cycle during the periods of ±150 % in 50 % increments before and after the apnoea/hypopnoea phase. In this subanalysis of 54 SERVE-HF patients, PVC burden was 32 % higher in the late hyperventilation period (50–100 % after apnoea/hypopnoea) compared to the apnoea/hypopnoea phase.

An improved machine learning-based prediction framework for early detection of events in heart failure patients using mHealth

An improved machine learning-based prediction framework for early detection of events in heart failure patients using mHealth

Effects of sodium-glucose co-transporter 2 inhibitors on heart failure events in chronic kidney disease: a systematic review and meta-analysis.

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors significantly reduce the risk for hospitalizations for heart failure (HF) in patients with diabetes, and HF; findings in patients with chronic kidney disease (CKD) are not uniform. We aimed to perform a meta-analysis exploring the effect of SGLT-2 inhibitors on HF events in patients with CKD and across subgroups defined by baseline kidney function. A systematic search in major electronic databases was performed. Randomized controlled trials providing data on the effect of SGLT-2 inhibitors on the primary outcome, time to hospitalization or urgent visit for worsening HF in patients with prevalent CKD at baseline or across subgroups stratified by baseline estimated glomerular-filtration-rate (eGFR) were included. Twelve studies (n=89,191 participants) were included in the meta-analysis. In patients with CKD, treatment with SGLT-2 inhibitors reduced the risk for HF events by 32% compared to placebo (hazard ratio [HR] 0.68; 95%CI 0.63-0.73). Reduction in HF events with SGLT-2 inhibitors was more prominent in patients with eGFR<60 ml/min/1.73m2 (HR 0.68; 95%CI 0.62-0.74) than in those with eGFR≥60 ml/min/1.73m2 (HR 0.76; 95%CI 0.69-0.83). Subgroup analysis according to type of SGLT-2 inhibitor showed a consistent treatment effect across all studied agents (p-subgroup-analysis=0.44). Sensitivity analysis including data from studies including only diabetic patients showed an even more pronounced effect in eGFR subgroup<60 ml/min/1.73m2 (HR 0.62; 95%CI 0.54-0.70). Treatment with SGLT-2 inhibitors led to a significant reduction in HF events in patients with CKD. Such findings may change the landscape of prevention of HF events in patients with advanced CKD. PROSPERO Registration number: CRD42022382857.

Abnormal circulating steroids refine risk of progression to heart failure in ischemic heart disease.

Patients with ischemic heart disease (IHD) experience a high incidence of progression to heart failure (HF) despite current therapies. We speculated that steroid hormone metabolic disorders distinct adverse phenotypes and contribute to HF. We measured 18 steroids using liquid chromatography with tandem mass spectrometry in 2023 patients from the Registry Study of Biomarkers in Ischemic Heart Disease (BIOMS-IHD), including 1091 patients with IHD in a retrospective discovery set and 932 patients with IHD in a multicentre validation set. Our outcomes included incident HF after a median follow-up of 4 years. We demonstrated steroid-based signatures of inflammation, coronary microvascular dysfunction and left ventricular hypertrophy that were associated with subsequent HF events in patients with IHD. In both cohorts, patients with a high steroid-heart failure score (SHFS) (>1) exhibited a greater risk of incident HF than patients with a low SHFS (≤1). The SHFS further improved the prognostic accuracy beyond clinical variables (net reclassification improvement of 0.628 in the discovery set and 0.299 in the validation set) and demonstrated the maximal effect of steroid signatures in patients with IHD who had lower B-type natriuretic peptide levels (pinteraction  = 0.038). A steroid-based strategy can simply and effectively identify individuals at higher HF risk who may derive benefit from more intensive follow-ups.

Recurrent heart failure hospitalizations in heart failure with preserved ejection fraction: an analysis of TOPCAT trial.

Recurrent heart failure hospitalization (HFH) is an important feature of the progression of heart failure (HF). In the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, we analysed risk factors for recurrent HFH events in HF patients with preserved ejection fraction (HFpEF) and developed a risk prediction model for recurrent HFH. This analysis focused on the subset of TOPCAT participants enrolled in the Americas (n=1767). Recurrent HFH was defined as two or more hospitalizations for HF during the follow-up period. Lasso regression and multivariate logistic regression were used to screen the risk factors, and the risk prediction model of recurrent HFH was established. During a median follow-up period of 3.4 (95% confidence interval: 3.3-3.6) years, 72.2% (542 of 751 total hospitalizations) of HFH events occurred in 9.4% (n=163) of patients with recurrent HFHs. Patients in the recurrent HFH group had higher cardiovascular mortality rate [6.2 per 100 patient-years (PY) vs. 3.8 per 100 PY, P=0.016] and all-cause mortality rate (10.0 per 100 PY vs. 6.8 per 100 PY, P=0.015) than those in the non-recurrent HFH group. The model consisting of nine predictors has moderate predictive power for recurrent HFH events in patients with HFpEF (AUC=0.75, Brier score=0.08). Decision curve analysis showed a net clinical benefit from the application of the prediction model. In patients with HFpEF, the majority of HFHs occur in a small proportion of patients with repeated hospitalizations, who typically have more comorbidities and are at higher risk of death. The predictive model developed in this study helps to identify patients at high risk of recurrent HFH.

Predictive value of protein-bound uremic toxins for heart failure in patients with chronic kidney disease.

This retrospective cohort study aimed to be the first to evaluate the association between plasma protein-bound uremic toxins (PBUTs) concentrations, echocardiographic parameters of heart failure (HF), and incident HF events in patients with chronic kidney disease (CKD) not on dialysis. Retrospective, single-centre, cohort study at the Ghent University Hospital, Belgium. Adults with CKD stages G1-G5, not on dialysis, could be included. Exclusion criteria were ongoing pregnancy, age <18years, active acute infection, active malignancy, history of transplantation, or a cardiovascular event within 3months prior to inclusion. Free and total concentrations of five PBUTs were quantified at baseline: indoxyl sulfate (IxS), p-cresyl sulfate (pCS), p-cresyl glucuronide (pCG), indole-3 acetic acid (IAA), and hippuric acid (HA). Patients were grouped into three echocardiographic categories: normal left ventricular ejection fraction (LVEF) and normal left ventricular end-diastolic pressure (LVEDP), normal LVEF and increased LVEDP, and reduced LVEF, based on available echocardiographic data in a time interval of ±6months around the plasma sample collection. A total of 523 patients were included between January 2011 and January 2014. Echocardiographic data within the predefined timeframe were available for 210 patients (40% of patients). Levels of pCG and pCS were significantly higher in patients with reduced (<50%) versus normal LVEF (P<0.05). After a median follow-up 5.5years, 43 (8.4%) patients reached the composite endpoint of hospitalization or mortality due to HF. Free fractions of IxS, pCS, and pCG showed the strongest association with clinical outcome: free IxS: HR 1.71 (95% CI 1.11-2.63; P=0.015), free pCS: HR 1.82 (95% CI 1.11-3.01; P=0.019), and free pCG: HR 1.67 (95% CI 1.08-2.58; P=0.020), and these results were independent of age, gender, body mass index, diabetes, and systolic blood pressure. In models that were also adjusted for serum creatinine, the free fractions of these PBUTs remained significant. Elevated free concentrations of IxS, pCG, and pCS were independently associated with an increased risk of HF events in non-dialysed CKD patients. Further research is necessary to confirm these findings and investigate the potential impact of PBUT-lowering interventions on HF events in this patient group.

Catheter ablation for atrial fibrillation in patients with heart failure with reduced versus preserved ejection fraction; a systematic review and meta-analysis

Abstract Background Catheter ablation is superior to pharmacological therapies for lowering adverse cardiovascular outcomes in patients with both atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). Yet, it is uncertain whether patients with heart failure with mildly reduced or preserved ejection fraction (HFpEF) derive the same treatment benefit from catheter ablation. Purpose This systematic review and meta-analysis aimed to assess whether the efficacy of AF catheter ablation in reducing all-cause mortality and heart failure events is different in patients with HFrEF versus HFpEF. Methods We searched MEDLINE, Embase, and Cochrane Central to September 2022 for randomized controlled trials in patients with heart failure comparing catheter ablation for AF with medical therapy (defined as rate or rhythm control with medications, device implantation, and/or cardioversion). The outcomes of interest were all-cause mortality and heart failure events (i.e. hospitalization or worsening). Pairs of reviewers systematically screened the eligible studies and used random-effects models to combine data. We contacted authors of eligible studies to obtain unpublished data on heart failure subgroups. We used an interaction p-value to test the statistical significance of difference between subgroups with HFrEF and HFpEF. Results A total of 8 studies (2118 participants, mean age: 65.6 years, 28.1% women) assessed the effect of catheter ablation on all-cause mortality in patients with AF and heart failure. We found no statistical evidence of a different effect for AF catheter ablation in reducing all-cause mortality in patients with HFrEF (196 events, RR 0.67, 95% CI: 0.50-0.90) compared to those with HFpEF (77 events, RR 0.95, 95% CI: 0.39-2.30) – p for subgroup differences=0.46. In addition, 7 studies (2057 participants, mean age: 65.8 years, 29% women) evaluated the effect of catheter ablation on heart failure events in patients with AF and heart failure. As compared to conventional medical therapies, AF catheter ablation significantly reduced the risk of heart failure events in patients with HFrEF (285 events, RR 0.59, 95% CI: 0.48-0.72); however, it had little or no effect on heart failure events in those with HFpEF (106 events, RR 0.93, 95% CI: 0.65-1.32). Interaction analysis showed significant effect modification for AF catheter ablation in patients with HFpEF – p for subgroup differences=0.03. Conclusion Catheter ablation is superior to conventional medical therapies for reducing all-cause mortality in patients with AF and heart failure. However, its beneficial effect on heart failure events may be limited to patients with HFrEF. The available evidence on patients with HFpEF is insufficient for a definitive conclusion. Future trials are warranted to study the prognostic effect of catheter ablation in patients with AF and HFpEF.All-cause MortalityHeart Failure Events

Prediction of acute heart failure events in patients with hypertrophic cardiomyopathy using RNA-Sequencing of plasma small non-coding RNAs

Abstract Background Hypertrophic cardiomyopathy (HCM) often causes acute heart failure (HF) events, which lead to worse quality of life and prognosis of patients with HCM. The recent emergence of cardiac myosin inhibitors to treat HCM highlights the clinical significance of identifying patients with HCM at high risk of developing acute HF events. However, no tools are available to predict acute HF events in HCM. Furthermore, the underlying molecular mechanisms responsible for the development of HF in HCM remain uncertain. Plasma RNA-sequencing (RNA-Seq) determines concentrations of thousands of small non-coding RNAs (sncRNAs) and has the potential to predict acute HF events in HCM. Purpose To predict acute HF events in patients with HCM using RNA-Seq of plasma sncRNAs and to determine signaling pathways dysregulated in those who subsequently experience acute HF events. Methods In this prospective, multi-center cohort study of patients with HCM, we conducted RNA-Seq of 3,740 plasma sncRNAs on 390 patients with HCM. The primary outcome was acute HF event defined as unplanned hospitalization due to HF. We developed a sncRNA-Seq-based model with linear discriminant analysis to predict acute HF events using data from one institution (training set, n=271). We also developed a reference model using clinical parameters with significant differences between patients with and without acute HF events in the training set. Then we tested the predictive ability in samples from the other institutions (test set, n=119), comparing the area under the receiver-operating-characteristic curve (AUC) between a combined model using the reference model plus the sncRNA-Seq-based model and the reference model using the Delong’s test. We also performed pathway analysis of microRNAs significantly (i.e., nominal P&amp;lt;0.05) associated with acute HF events. Results During a median follow-up time of 2.5 (interquartile 1.7–4.9) years, a total of 37 patients in the training set (14%) and 15 in the test set (13%) experienced an acute HF event. The model combining the reference model with the sncRNA-Seq-based machine learning model developed in the training set significantly outperformed the reference model (AUC 0.86 [95% confidence interval (CI) 0.74–0.97] vs. 0.68 [0.52–0.85], P=0.01, Figure) in the test set. The pathway analysis exhibited that both known pathways related to fibrosis, inflammation, and cell proliferation (e.g., the TGF-β signaling pathway) and novel pathways (e.g., the mTOR signaling pathway) were dysregulated with false discovery rate &amp;lt;0.01 in patients with HCM who subsequently experienced acute HF events (Table). Conclusions This study serves as the first to demonstrate the ability of plasma sncRNA-Seq to predict acute HF events in patients with HCM. Patients who subsequently experienced acute HF events exhibited dysregulation of both known and novel pathways.FigureTable

Validation of a new CPET multivariable score to predict cardiovascular events in heart failure patients

Abstract Introduction Cardiopulmonary exercise testing (CPET) is recommended in patients with heart failure (HF) to optimize exercise prescription and as part of the evaluation for heart transplantation. Recently, a new multivariable score (MVS) was proposed as a powerful method to predict HF events with an optimal cut-off value of 120. Purpose We aimed to evaluate the prognostic value of this tool in patients with HF. Methods We conducted a single-centre study assessing consecutive patients with HF who underwent CPET from 2013 to 2017. Classic and recently proposed variables were collected, including peak O2 uptake (pVO2), minute ventilation–CO2 production (VE/VCO2 slope), partial pressure of end-tidal CO2 at the anaerobic threshold (PETCO2L), circulatory power (CP=pVO2 x peak SBP), and ventilatory power (VP=peak SBP/(VE/VCO2) slope). The score was calculated as follows: (pVO2 × 2.194) + (PETCO2L × 1.545) + (LVEF × 1.134) + (HR × 1.055; 0 if AF, 1 if sinus rhythm). The primary outcome was a composite of HF hospitalization, heart transplant, and all-cause mortality. Results We included 212 patients 76.9% male and with a mean age of 55.4±10.9 years-old. The most frequent aetiology was dilated cardiomyopathy (43.9%) followed by ischaemic heart disease (38.7%). Accordingly, the mean left ventricle ejection fraction was 29±13%. Additionally, 39.8% had atrial fibrillation. The most used exercise protocol was the modified Naughton (76.6%). Mean pVO2 was 16.7±5.9mL O2·kg−1·min−1, median VE/VCO2 slope was 37.5 [32.7-44.3], and PETCO2L 33.5±5.2mmHg. Mean VP was 3.46±1.31mmHg while the median CP was 1927 [1427-2697]mmHg·min/mL/kg. The mean MVS was 116.2±23.1. Despite weak, there were significant positive correlations between the MVS and both VP (r=0.59, p&amp;lt;0.01) and CP (rs=0.64, p&amp;lt;0.01). After a median follow-up of 71 [49-81] months, the primary outcome occurred in 66.0% of patients (rehospitalization, heart transplant, and all-cause death occurred in 56.1%, 25.9%, and 32.5%, respectively). The new CPET MVS was associated with the primary outcome (p&amp;lt;0.01). Additionally, patients with MVS &amp;lt;120 had a higher rate of the primary outcome (83.2% vs. 39.1%, p&amp;lt;0.01). Kaplan-Meier estimates of tthe primary outcome according to the optimal cut-off value of 120 are shown in Figure 1A. Receiver operating characteristic curve revealed that the MVS has higher discriminative power for the primary endpoint (AUC 0.80, p&amp;lt;0.01) compared to pVVO2, VP, and CP (Figure 1B). Conclusion The novel multivariable score is associated with the composite of HF hospitalization, heart transplant, and all-cause mortality in patients with heart failure, enhancing the role of CPET in risk stratification.

Interleukin-6 plasma levels predict mortality and heart failure events in cardiac transthyretin amyloidosis

Abstract Background Low-grade systemic inflammation is a key component in the pathophysiology of heart failure (HF). In particular, the pleiotropic effects of interleukin-6 (IL-6) signaling are of interest as circulating IL-6 levels are associated with mortality in HF patients. Purpose The purpose of this study was to investigate whether IL-6 plasma levels predict mortality and HF events in patients with cardiac transthyretin amyloidosis (ATTR-CM). Methods This was an analysis of a prospective single-center cohort study comprising 98 ATTR-CM patients. The endpoint was defined as a composite of all-cause mortality and worsening HF events. HF events included HF related hospitalizations and urgent outpatient clinic visits with concomitant intravenous diuretic treatment. Follow-up data were collected using central medical records. Kaplan-Meier estimates and Cox regression analyses were calculated to assess the association between IL-6 and the composite endpoint. Moreover, receiver operator characteristics (ROC) analysis was performed to evaluate the predictive accuracy of IL-6 for the composite endpoint. Results Median age was 79 years (76-81), 86 patients (88%) were male, and 46 patients (47%) received the transthyretin (TTR) stabilizer tafamidis at baseline. Median NT-proBNP levels were 2813 pg/ml (1365-4856), mean estimated glomerular filtration rate (eGFR) was 57.9±17.6 ml/min/1.73m², and median urine protein to creatinine ratio (UPCR) was 122.0 mg/g (89.8-204.5). Median IL-6 plasma levels were 4.9 pg/ml (3.0-9.4). During a median observation period of 21.2 months (11.4-32.4), 27 patiens (28%) reached the composite endpoint. IL-6 levels were associated with the composite endpoint (hazard ratio = 1.028, 95% confidence interval = 1.004 to 1.051; p = 0.012). The association was independent of age, TTR stabilizing medication, log-transformed and eGFR-adjusted NT-proBNP levels, as well as UPCR. The area under the ROC curve for IL-6 was 0.70 (95% confidence interval = 0.59 to 0.81; p = 0.003). The optimal cutoff value was 5.3 pg/ml, as determined by Youden’s index, with a sensitivity of 70% and specificity of 66%. Kaplan-Meier estimates demonstrated a mean survival time of 1030 days (95% confidence interval = 911 to 1150) for the study population. A statistically significant difference between the survival rates of ATTR-CM patients with IL-6 levels ≥5.3 pg/ml and those with IL-6 levels below the threshold was indicated by the log-rank test (p = 0.002). Conclusion Circulating levels of IL-6 independently predicted adverse outcomes in patients with ATTR-CM. IL-6 plasma levels may be useful for identifying a high-risk ATTR-CM subpopulation.Tablewith baseline characteristicsFigurewith Kaplan-Meier estimates

Associations between baseline heart rate and blood pressure and time to events in HFrEF patients: data from the QUALIFY international registry

Abstract Aims Low systolic blood pressure (SBP) and high resting heart rate (RHR) are both risk indicators for heart failure (HF) outcomes. The purpose of this analysis is to evaluate the associations between RHR and SBP at baseline and time to events in HF patients with reduced ejection fraction (HFrEF) in the QUALIFY international registry. Methods and results The QUALIFY registry enrolled 7317 patients with left ventricular ejection fraction (LVEF) ≤40% and previous HF hospitalization within 1–15 months. Complete Follow-up data were available from 5138 patients. The relationship between RHR and SPB on outcomes were analyzed according to baseline values as high RHR (H-RHR) ≥ 75 vs. low RHR (L-RHR) &amp;lt; 75 bpm) and high SBP (H-SBP): ≥ 110 vs. low SBP (L-SBP): &amp;lt;110 mmHg and analyzed according to each of the following 4 phenotypes: (H-RHR/L-SBP, L-RHR/L-SBP, H-RHR/H-SBP and L-RHR/H-SBP (reference group)). Compared to patients with reference group, patients with L-RHR/L-SBP had the highest all-cause mortality (hazard ratio (HR) 2,57, 95% CI 1.85–3.56 vs. HR 0.80, 95% CI 0.72–0.89, P&amp;lt;0.001). After adjustment for age, Sex, NYHA, AF and eGFR rate, all-cause mortality remains the highest between the all groups (HR 2.62, 95% CI 1.88–3.66 P = &amp;lt;0.001), followed by L-RHR/L-SBP (HR 1.74, 95% CI 1.24–2.45 P = 0.001 and H-RHR/H-SBP (HR 1.44, 95% CI 1.08–1.92 P = 0.01). H-RHR/L-SBP and after adjustment was associated with the worst outcomes for other endpoints: CV death and HF hospitalization HR 1.83, CI 1.66-2.42, p = &amp;lt;0.001), CV mortality (HR 2.7, CI 1.69-4.33, p = &amp;lt;0.001) and HF hospitalization (HR 1.71, CI 1.30-2.25, p = &amp;lt;0.001) Conclusion HFrEF patients, who have previously been hospitalized for HF presented with L-SBP and H-RHR, were at greater risk for all case mortality and CV death and HF hospitalization