Group In Chronic Heart Failure Research Articles

Cardiac contractility modulation in heart failure with reduced ejection fraction patients with QRS duration 120–149 ms: Reduction in heart failure hospitalizations and improvement in functional outcome

BackgroundA subset of heart failure (HF) patients qualifies for cardiac resynchronization therapy (CRT). However, a 30% CRT nonresponder rate persists, with patients having narrower QRS durations (ie, QRSd 120–149 ms) receiving less or inconsistent benefit. Cardiac contractility modulation (CCM) may be an important alternative therapy option but has largely been evaluated only in HF patients with QRSd <120 ms. ObjectivesThe purpose of this study was to evaluate the impact of CCM on HF-related hospitalizations and on left ventricular ejection fraction (LVEF) as well as quality of life in HF patients with QRSd 120–149 ms compared to QRSd <120 ms. MethodsThe CCM-REG Registry enrolled 503 HF patients with follow-up up to 2 years. Hospitalization rates were available for 1 year preimplant. Safety was assessed by comparison of actual vs Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score– or Seattle Heart Failure Model (SHFM)–predicted mortality. ResultsAmong 111 of 455 subjects with QRSd 120–149 ms (mean QRSd 130 ± 8 ms; age 68 ± 10 years; 20% female; LVEF 29% ± 9%; 82% New York Heart Association [NYHA] class III), CCM diminished HF-related hospitalization rate by 72% (pre- vs postimplant 0.90 vs 0.25 events per patient-year over 2 years; P <.001). LVEF improved by 7% ± 8% (P = .01 vs baseline), Minnesota Living with Heart Failure Questionnaire score by 10 ± 23 points (P = .01 vs baseline), and NYHA class by 0.5 ± 0.7 classes (<0.001 vs baseline). The effect size was similar to that in QRSd <120 ms patients. Mortality within the first year was 19% in QRSd 120–149 ms patients (ie, not significantly different from the MAGGIC score or SHFM prediction). ConclusionsCCM significantly improved HF control in NYHA class III HF with reduced ejection fraction patients with moderately prolonged QRSd 120–149 ms. The effect was similar to that in patients with QRSd <120 ms.

Urinary Proteomics and Outcomes in Heart Failure With Preserved Ejection Fraction.

Although several studies have addressed plasma proteomics in heart failure with preserved ejection fraction, limited data are available on the prognostic value of urinary proteomics. The objective of our study was to identify urinary proteins/peptides associated with death and heart failure admission in patients with heart failure with preserved ejection fraction. The study population included participants enrolled in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial). The relationship between urine protein levels and the risk of death or heart failure admission was assessed using Cox regression, in both nonadjusted analyses and adjusting for urine creatinine levels, and the MAGGIC (Meta-Analysis Global Group in Chronic Heart Failure) score. A total of 426 (12.4%) TOPCAT participants had urinary protein data and were included. There were 40 urinary proteins/peptides significantly associated with death or heart failure admission in nonadjusted analyses, 21 of which were also significant adjusted analyses. Top proteins in the adjusted analysis included ANGPTL2 (angiopoietin-like protein 2) (hazard ratio [HR], 0.5731 [95% CI, 0.47-0.7]; P=3.13E-05), AMY2A (α amylase 2A) (HR, 0.5496 [95% CI, 0.44-0.69]; P=0.0001), and DNASE1 (deoxyribonuclease-1) (HR, 0.5704 [95% CI, 0.46-0.71]; P=0.0002). Higher urinary levels of proteins involved in fibrosis (collagen VI α-1, collagen XV α-1), metabolism (pancreatic α-amylase 2A/B, mannosidase α class 1A member 1), and inflammation (heat shock protein family D member 1, inducible T cell costimulatory ligand) were associated with a lower risk of death or heart failure admission. Our study identifies several novel associations between urinary proteins/peptides and outcomes in heart failure with preserved ejection fraction. Many of these associations are independent of clinical risk scores and may aid in risk stratification in this patient population.

Prognostic value of growth differentiation factor-15 in heart failure among whole ejection fraction phenotypes.

The utility of growth differentiation factor-15 (GDF-15) in predicting long-term adverse outcomes in heart failure (HF) patients is not well established. This study explored the relationship between GDF-15 levels and adverse outcomes in HF patients across various ejection fraction (EF) phenotypes associated with coronary heart disease (CHD) and evaluated the added prognostic value of incorporating GDF-15 into the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score-based model. This single-centre cohort study included 823 HF patients, categorized into 230 (27.9%) reduced EF (HFrEF), 271 (32.9%) mid-range EF (HFmrEF), and 322 (39.1%) preserved EF (HFpEF) groups. The median age was 68.0years (range: 56.0-77.0), and 245 (29.8%) were females. Compared with the HFrEF and HFmrEF groups, the HFpEF group had a higher GDF-15 concentration (P=0.002) and a higher MAGGIC risk score (P<0.001). We examined the associations between GDF-15 levels and the risks of all-cause mortality and HF rehospitalization using Cox regression models. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) metrics were employed to assess the incremental prognostic value. During the 9.4year follow-up period, 425 patients died, and 484 were rehospitalized due to HF. Multivariate Cox regression analysis revealed that elevated GDF-15 levels were significantly associated with an increased risk of all-cause mortality [hazard ratio (HR)=1.36, 95% confidence interval (CI): 1.20-1.54; P<0.001] and HF rehospitalization (HR=1.75, 95% CI: 1.57-1.95; P<0.001) across all HF phenotypes. This association remained significant when GDF-15 was treated as a categorical variable (high GDF-15 group: all-cause death: HR=1.73, 95% CI: 1.40-2.14; P<0.001; HF rehospitalization: HR=3.37, 95% CI: 2.73-4.15; P<0.001). Inclusion of GDF-15 in the MAGGIC risk score-based model provided additional prognostic value for all HF patients (Δ C-index=0.021, 95% CI: 0.002-0.041; IDI=0.011, 95% CI: 0.001-0.025; continuous NRI=0.489, 95% CI: 0.174-0.629) and HF rehospitalization (Δ C-index=0.034, 95% CI: 0.005-0.063; IDI=0.021, 95% CI: 0.007-0.032; continuous NRI=0.307, 95% CI: 0.147-0.548), particularly in the HFpEF subgroup. GDF-15 is identified as an independent risk factor for adverse outcomes in HF patients across the entire EF spectrum in the context of CHD. Integrating GDF-15 into the MAGGIC risk score-based model enhances its prognostic capability for adverse outcomes in the general HF population. This incremental prognostic effect was observed specifically in the HFpEF subgroup and not in other subgroups.

Frailty and Metabolic Vulnerability in Heart Failure: A Community Cohort Study.

Frailty is common in heart failure (HF) and is associated with death but not routinely captured clinically. Frailty is linked with inflammation and malnutrition, which can be assessed by a novel plasma multimarker score: the metabolic vulnerability index (MVX). We sought to evaluate the associations between frailty and MVX and their prognostic impact. In an HF community cohort (2003-2012), we measured frailty as a proportion of deficits present out of 32 physical limitations and comorbidities, MVX by nuclear magnetic resonance spectroscopy, and collected extensive longitudinal clinical data. Patients were categorized by frailty score (≤0.14, >0.14 and ≤0.27, >0.27) and MVX score (≤50, >50 and ≤60, >60 and ≤70, >70). Cox models estimated associations of frailty and MVX with death, adjusted for Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Uno's C-statistic measured the incremental value of MVX beyond frailty and clinical factors. Weibull's accelerated failure time regression assessed whether MVX mediated the association between frailty and death. We studied 985 patients (median age, 77; 48% women). Frailty and MVX were weakly correlated (Spearman's ρ=0.21). The highest frailty group experienced an increased rate of death, independent of MVX, MAGGIC score, and NT-proBNP (hazard ratio, 3.3 [95% CI, 2.5-4.2]). Frailty improved Uno's c-statistic beyond MAGGIC score and NT-proBNP (0.69-0.73). MVX only mediated 3.3% and 4.5% of the association between high and medium frailty groups and death, respectively. In this HF cohort, frailty and MVX are weakly correlated. Both independently contribute to stratifying the risk of death, suggesting that they capture distinct domains of vulnerability in HF.

Incremental Value of a Metabolic Risk Score for Heart Failure Mortality: A Population-Based Study.

Heart failure is heterogeneous syndrome with persistently high mortality. Nuclear magnetic resonance spectroscopy enables high-throughput metabolomics, suitable for precision phenotyping. We aimed to use targeted metabolomics to derive a metabolic risk score (MRS) that improved mortality risk stratification in heart failure. Nuclear magnetic resonance was used to measure 21 metabolites (lipoprotein subspecies, branched-chain amino acids, alanine, GlycA (glycoprotein acetylation), ketone bodies, glucose, and citrate) in plasma collected from a heart failure community cohort. The MRS was derived using least absolute shrinkage and selection operator penalized Cox regression and temporal validation. The association between the MRS and mortality and whether risk stratification was improved over the Meta-Analysis Global Group in Chronic Heart Failure clinical risk score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels were assessed. The study included 1382 patients (median age, 78 years, 52% men, 43% reduced ejection fraction) with a 5-year survival rate of 48% (95% CI, 46%-51%). The MRS included 9 metabolites measured. In the validation data set, a 1 standard deviation increase in the MRS was associated with a large increased rate of death (hazard ratio, 2.2 [95% CI, 1.9-2.5]) that remained after adjustment for Meta-Analysis Global Group in Chronic Heart Failure score and NT-proBNP (hazard ratio, 1.6 [95% CI, 1.3-1.9]). These associations did not differ by ejection fraction. The integrated discrimination and net reclassification indices, and Uno's C statistic, indicated that the addition of the MRS improved discrimination over Meta-Analysis Global Group in Chronic Heart Failure and NT-proBNP. This MRS developed in a heart failure community cohort was associated with a large excess risk of death and improved risk stratification beyond an established risk score and clinical markers.

S2I2N0-3 score predicts short- and long-term mortality and morbidity in HFrEF: a post-hoc analysis of the GUIDE-IT trial.

This study investigated the S2I2N0-3 score, a simple tool comprising stroke history, insulin-treated diabetes, and N-terminal pro-brain natriuretic peptide, for forecasting mortality and morbidity in heart failure (HF) with reduced ejection fraction (HFrEF). Analysing 890 GUIDE-IT HFrEF trial participants, we stratified them by baseline S2I2N0-3 risk score into three risk groups. We examined the score's association with five adverse outcomes over short (90days) and extended periods (median follow-up of 15months) using Cox and competing risk models. Our analysis revealed significant positive associations between the S2I2N0-3 strata and adverse outcomes. When analysed as a continuous variable, each point increment of the S2I2N0-3 score was associated with a higher risk of short- and long-term cardiovascular death [short term: hazard ratio (HR) 1.43, 95% confidence interval (CI) 1.03-1.98; long term: HR 1.18, 95% CI 1.02-1.38], all-cause death (HR 1.52, 95% CI 1.12-2.07; HR 1.18, 95% CI 1.03-1.36), HF hospitalization (HR 1.39, 95% CI 1.20-1.62; HR 1.18, 95% CI 1.06-1.31), any hospitalization (HR 1.19, 95% CI 1.06-1.34; HR 1.09, 95% CI 1.00-1.19), and the composite outcome of cardiovascular death and HF hospitalization (HR 1.39, 95% CI 1.21-1.60; HR 1.17, 95% CI 1.06-1.30). The S2I2N0-3 demonstrated reliable prognostic value, with C-indices ranging from 0.619 to 0.753 across outcomes and time points. When compared with the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score using Z-statistics, net reclassification index, and integrated discrimination improvement, the S2I2N0-3 showed comparable predictive power for all outcomes during both short- and long-term follow-ups. The S2I2N0-3 risk score had modest predictive values for both short- and long-term clinical outcomes in HFrEF patients, offering equivalent performance to the established MAGGIC score.

Association between haemoglobin, albumin, lymphocytes, and platelets and mortality in patients with heart failure.

The combination of haemoglobin, albumin, lymphocytes, and platelets (HALP) is a new metric used to assess patient prognosis in many diseases. This study aimed to assess the relationship between HALP and short- and long-term mortality in patients with heart failure. This retrospective cohort study included adult patients with heart failure who were hospitalized between 2019 and 2021. The primary outcomes were 1-month mortality and 1-year mortality. The multivariable logistic regression analysis was used to evaluate the association between HALP and the risk of mortality. Stratified analyses were conducted based on New York Heart Association functional classification (NYHA) stage (II/III, IV) and left ventricular ejection fraction (LVEF, <50%, ≥50%). The area under the receiver operating characteristic curve (AUC) was used to evaluate the ability of HALP, prognostic nutritional index (PNI), C-reactive protein (CRP), and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC-HF) risk score in predicting mortality in patients with heart failure. A total of 730 patients with heart failure were included, of whom 61 (8.36%) died within 1month and 77 (10.55%) died within 1year. High HALP scores were associated with a reduced risk of 1-month mortality (odds ratio (OR)=0.978, 95% confidence interval (CI): 0.963-0.992, P=0.003) and 1-year mortality (OR=0.987, 95% CI: 0.977-0.997, P=0.009) in patients with heart failure. In patients with different NYHA stages or LVEF levels, high HALP scores were correlated with a reduced risk of 1-year mortality in patients with NYHA stage II/III (OR=0.978, 95% CI: 0.957-1.000, P=0.045) or LVEF ≥50% (OR=0.970, 95% CI: 0.945-0.996, P=0.024). The AUC for HALP, PNI, CRP, and MAGGIC-HF to predict 1-year mortality in patients with heart failure were 0.677 (95% CI: 0.619-0.735), 0.666 (95% CI: 0.608-0.723), 0.638 (95% CI: 0.572-0.704), and 0.654 (95% CI: 0.591-0.717), respectively. HALP may be a potential marker for predicting mortality in patients with heart failure. Further exploration based on HALP may yield better clinical predictors of prognosis in patients with heart failure.

The WATCH-DM risk score estimates clinical outcomes in type 2 diabetic patients with heart failure with preserved ejection fraction

The coexistence of heart failure is frequent and associated with higher mortality in patients with type 2 diabetes (T2DM), and its management is a critical issue. The WATCH-DM risk score is a tool to predict heart failure in patients with type 2 diabetes mellitus (T2DM). We investigated whether it could estimate outcomes in T2DM patients with heart failure with preserved ejection fraction (HFpEF). The WATCH-DM risk score was calculated in 418 patients with T2DM hospitalized for HFpEF (male 49.5%, age 80 ± 9 years, HbA1c 6.8 ± 1.0%), and they were divided into the “average or lower” (≤ 10 points), “high” (11–13 points) and “very high” (≥ 14 points) risk groups. We followed patients to observe all-cause death for 386 days (median). We compared the area under the curve (AUC) of the WATCH-DM score for predicting 1-year mortality with that of the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score and of the Barcelona Bio-Heart Failure Risk (BCN Bio-HF). Among the study patients, 108 patients (25.8%) had average or lower risk scores, 147 patients (35.2%) had high risk scores, and 163 patients (39.0%) had very high risk scores. The Cox proportional hazard model selected the WATCH-DM score as an independent predictor of all-cause death (HR per unit 1.10, 95% CI 1.03 to 1.19), and the “average or lower” risk group had lower mortality than the other groups (p = 0.047 by log-rank test). The AUC of the WATCH-DM for 1-year mortality was 0.64 (95% CI 0.45 to 0.74), which was not different from that of the MAGGIC score (0.72, 95% CI 0.63 to 0.80, p = 0.08) or that of BCN Bio-HF (0.70, 0.61 to 0.80, p = 0.25). The WATCH-DM risk score can estimate prognosis in T2DM patients with HFpEF and can identify patients at higher risk of mortality.

Meta-Analysis Global Group in Chronic Heart Failure score for the prediction of mortality in valvular heart disease.

Valvular heart disease (VHD) is one of the leading causes of heart failure. Clinically significant VHD can induce different patterns of cardiac remodelling, and risk stratification is challenging in patients with various degrees of cardiac dysfunction. The study aimed to investigate the prognostic implications of Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score in patients with VHD. This study used data from the China Valvular Heart Disease (China-VHD) registry, which was a multicentre, prospective, observational cohort study for patients with significant (at least moderate) VHD. In total, 10446 patients with moderate or greater VHD from the China-VHD study were included in the present analysis. The primary outcome of interest was all-cause mortality within 2years. Among 10446 patients with VHD, the mean age was 61.98±13.47years, and 5819 (55.7%) were male. During 2years of follow-up, 895 (8.6%) patients died. The MAGGIC score was monotonically and independently associated with mortality in both total cohort [adjusted hazard ratio: 1.095, 95% confidence interval (CI): 1.084-1.107, P<0.001] and most types of VHD (aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid regurgitation, mixed aortic stenosis and aortic regurgitation, and multiple VHD). The score was also an independent prognostic factor in patients with or without symptoms or preserved left ventricular ejection fraction (LVEF) and exhibited both satisfactory discrimination and calibration properties in predicting mortality. The prognostic value of MAGGIC score was robust in most quartiles of N-terminal pro-brain natriuretic peptide level, with no significant interaction observed (Pinteraction =0.498). Compared with the EuroSCORE II, the MAGGIC score achieved significantly better predictive performance in overall population [C index: 0.769 vs. 0.727; net reclassification improvement index (95% CI): 0.354 (0.313-0.396), P<0.001; integrated discrimination improvement index (95% CI): 0.069 (0.052-0.085), P<0.001] and in subgroups of patients divided by therapeutic strategy, LVEF, symptomatic status, stage of VHD, and aetiology of VHD. The MAGGIC score is a reliable prognostic factor across the range of cardiac dysfunction in VHD and may assist in risk stratification and guide clinical decision-making.

Association and Prognostic Value of Multidomain Frailty Defined by Cumulative Deficit and Phenotype Models in Patients With Heart Failure

BackgroundFrailty is associated with a poor prognosis in older patients with heart failure (HF). However, multidomain frailty assessment tools have not been established in patients with HF, and the association between the frailty phenotype and the deficit-accumulation frailty index in these patients is unclear. We aimed to understand this relationship and evaluate the prognostic value of the deficit-accumulation frailty index in older patients with HF. MethodsWe retrospectively analyzed FRAGILE-HF cohort, which consisted of prospectively registered hospitalized patients with HF aged ≥ 65 years. The frailty index was calculated using 34 health-related items. The physical, social, and cognitive domains of frailty were evaluated using a phenotypic approach. The primary endpoint was all-cause mortality. ResultsAmong 1027 patients with HF (median age, 81 years; male, 58.1%; median frailty index, 0.44), a higher frailty index was associated with a higher prevalence in all domains of cognitive, physical, and social frailty defined by the phenotype model. During the 2-year follow-up period, a higher frailty index was independently associated with all-cause death even after adjustment for Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score plus log B-type natriuretic peptide (per 0.1 increase: hazard ratio, 1.21; 95% confidence interval, 1.07-1.37; P = 0.002). The addition of the frailty index to the baseline model yielded statistically significant incremental prognostic value (net reclassification improvement, 0.165; 95% confidence interval, 0.012-0.318; P = 0.034). ConclusionsA higher frailty index was associated with a higher prevalence of all domains of frailty defined by the phenotype model and provided incremental prognostic information with pre-existing risk factors in older patients with HF.

Prognostic value of liver fibrotic markers in patients with heart failure

Abstract Background One of the major comorbidities in patients with heart failure (HF) is hepatic dysfunction, which may occur with prolonged hepatic hypoperfusion and congestion due to HF. Although several liver fibrotic markers are associated with prognosis in patients with HF, the optimal markers for outcome prediction remain unclear. Purpose The aim of this study was to simultaneously investigate the prognostic value of liver fibrotic markers and the associations between these markers and clinical parameters in HF patients without organic liver disease. Methods We prospectively examined 211 consecutive patients with chronic HF (116 male, mean age 66 ± 14 years, LVEF 48 ± 17%) between April 2018 and August 2021, excluding those with organic liver disease, using liver magnetic resonance imaging and ultrasound. We measured seven representative liver fibrotic markers, including hyaluronic acid, type III procollagen N-terminal peptide (P-III-P), type IV collagen 7s domain, mac-2 binding protein glycosylation isomer (M2BPGi), platelet ratio index (APRI), fibrosis 4 index (FIB-4), and FibroIndex. The primary outcome of interest was the composite of all-cause death and hospitalisation for HF. Results During a median follow-up period of 747 (interquartile range 465-1042) days, the primary outcome occurred in 45 patients (21%), including 15 (7%) all-cause deaths and 30 (14%) hospitalisations for HF. Patients with higher hyaluronic acid and P-III-P levels showed a significantly higher incidence of the primary outcome than those without (P &amp;lt;0.001 and P = 0.005, respectively). Multivariable Cox regression analysis showed that hyaluronic acid and P-III-P levels were independently associated with the risk of the primary outcome (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.18-2.87 and HR 2.89, 95% CI 1.32-6.34, respectively) even after adjustment for the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score, whereas other five liver fibrotic markers were not associated with the primary outcome. Discriminative value of the MAGGIC score for the primary outcome was significantly increased by adding hyaluronic acid and P-III-P levels (Harrel’s c-statistics; from 0.717 to 0.752 and 0.745, respectively) with significant net reclassification improvement (38% and 52%, respectively). Hyaluronic acid was predominantly correlated with age, haemoglobin, serum albumin, troponin T, N-terminal pro-brain natriuretic peptide (NT-proBNP), and pulmonary artery compliance (Figure). P-III-P levels were correlated with haemoglobin, estimated glomerular filtration rate, alkaline phosphatase, and NT-proBNP levels (Figure). Conclusion Among the representative liver fibrotic markers, hyaluronic acid and P-III-P might be optimal for outcome prediction in HF patients without organic liver disease. Hyaluronic acid and P-III-P levels were predominantly associated with several key prognostic indicators of HF simultaneously.

Relationship between baseline electrocardiographic measurements and outcomes in patients with high-risk heart failure: insights from the VerICiguaT Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial.

Whether electrocardiographic (ECG) measurements predict mortality in chronic heart failure with reduced ejection fraction (HFrEF) is unknown. We studied 4880 patients from the Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction (VICTORIA) trial with a baseline 12-lead ECG. Associations between ECG measurements and mortality were estimated as hazard ratios (HR) and adjusted for the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score, N-terminal pro-B-type natriuretic peptide, and index event. Select interactions between ECG measurements, patient characteristics and mortality were examined. Over a median of 10.8 months, there were 824 cardiovascular (CV) deaths (214 sudden) and 1005 all-cause deaths. Median age was 68 years (interquartile range [IQR] 60-76), 24% were women, median ejection fraction was 30% (IQR 23-35), 41% had New York Heart Association class III/IV, and median MAGGIC score was 24 (IQR 19-28). After multivariable adjustment, significant associations existed between heart rate (per 5 bpm: HR 1.02), QRS duration (per 10 ms: HR 1.02), absence of left ventricular hypertrophy (HR 0.64) and CV death, and similarly so with all-cause death (HR 1.02; HR 1.02; HR 0.61, respectively). Contiguous pathologic Q waves were significantly associated with sudden death (HR 1.46), and right ventricular hypertrophy with all-cause death (HR 1.44). The only sex-based interaction observed was for pathologic Q waves on CV (men: HR 1.05; women: HR 1.64, pinteraction = 0.024) and all-cause death (men: HR 0.99; women: HR 1.57; pinteraction = 0.010). Whereas sudden death doubled in females, it did not differ among males (male: HR 1.25, 95% confidence interval [CI] 0.87-1.79; female: HR 2.50, 95% CI 1.23-5.06; pinteraction = 0.141). Routine ECG measurements provide additional prognostication of mortality in high-risk HFrEF patients, particularly in women with contiguous pathologic Q waves.

Exercise Oscillatory Ventilation Improves Heart Failure Prognostic Scores.

Several heart failure (HF) prognostic risk scores are available to guide the ideal time for listing candidates for a heart transplant (HTx). The detection of exercise oscillatory ventilation (EOV) during cardiopulmonary exercise testing (CPET) is associated with advanced HF and a worse prognosis, and yet it is not accounted for in these risk scores. Therefore, this study aimed to assess whether EOV further adds prognostic value to HF scores. A single-centre retrospective cohort study was undertaken of consecutive HF patients with reduced ejection fraction (HFrEF) who underwent CPET from 1996 to 2018. The Heart Failure Survival Score (HFSS), Seattle Heart Failure Model (SHFM), Meta-analysis Global Group In Chronic Heart Failure (MAGGIC), and Metabolic Exercise Cardiac Kidney Index (MECKI) were calculated. The added value of EOV on top of those scores was assessed using a Cox proportional hazard model. The added discriminative power was also assessed by receiver operating characteristic curve comparison. A total of 390 HF patients with a median age of 58 (IQR 50-65) years were investigated, of whom 78% were male and 54% had ischaemic heart disease. The median peak oxygen consumption was 15.7 mL/kg/min (IQR 12.8-20.1). Exercise oscillatory ventilation was detected in 153 (39.2%) patients. Over a median follow-up of 2 years, 61 patients died (49 due to a cardiovascular reason) and 54 had a HTx. Exercise oscillatory ventilation independently predicted the composite outcome of all-cause death and HTx. Furthermore, the presence of this ventilatory pattern significantly improved the prognostic performance of both HFSS and MAGGIC scores. Exercise oscillatory ventilation was often found in a cohort of HF patients with reduced LVEF who underwent CPET. It was found that EOV added further prognostic value to contemporary HF scores, suggesting that this easily obtained parameter should be included in future modified HF scores.

Heart failure risk scores in advanced heart failure patients: insights from the LEVO-D registry.

The prevalence of advanced heart failure (HF) is increasing due to the growing number of patients with HF and their better treatment and survival. There is a scarcity of data on the accuracy of HF web-based risk scores in this selected population. This study aimed to assess mortality prediction performance of the Meta-Analysis Global Group in Chronic HF (MAGGIC-HF) risk score and the model of the Barcelona Bio-HF Risk Calculator (BCN-Bio-HF) containing N terminal pro brain natriuretic peptide in HF patients receiving intermittent inotropic support with levosimendan as destination therapy. Four hundred and three advanced HF patients from 23 tertiary hospitals in Spain receiving intermittent inotropic support with levosimendan as destination therapy were included. Discrimination for all-cause mortality was compared by area under the curve (AUC) and Harrell's C-statistic at 1year. Calibration was assessed by calibration plots comparing observed versus expected events based on estimated risk by each calculator. The included patients were predominantly men, aged 71.5 [interquartile range 64-78] years, with reduced left ventricular ejection fraction (27.5±9.4%); ischaemic heart disease was the most prevalent aetiology (52.5%). Death rate at 1year was 26.8%, while the predicted 1-year mortality by BCN-Bio-HF and MAGGIC-HF was 17.0% and 22.1%, respectively. BCN-Bio-HF AUC was 0.66 (Harrell's C-statistic 0.64), and MAGGIC-HF AUC was 0.62 (Harrell's C-statistic 0.61). The two evaluated risk scores showed suboptimal discrimination and calibration with an underestimation of risk in advanced HF patients receiving levosimendan as destination therapy. There is a need for specific scores for advanced HF.

The Relationship between the MAGGIC Score and Cardiorenal Syndrome in Patients with Acute Decompensated Heart Failure with Reduced Ejection Fraction.

The Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) is a scoring system that is easy to use in outpatient clinics or at the bedside, and was developed to predict the survival of heart failure patients after hospitalization. This study aims to evaluate the relationship between the MAGGIC score and cardiorenal syndrome (CRS) in patients with acute decompensated heart failure with reduced ejection fraction (HFrEF). This retrospective, single-center study, included 706 patients with New York Heart Association II-IV who were hospitalized and discharged for acute decompensated heart failure between 2016 and 2021. CRS type 1 was defined as acute worsening of cardiac function leading to renal dysfunction. Patients were divided into two groups: those with CRS and those without. The MAGGIC score of all patients was determined. The primary outcome was the occurrence of CRS. CRS developed in 132 patients. The MAGGIC score was higher in CRS (+) patients compared to CRS (-) patients (30.70 ± 8.09 vs. 23.96 ± 5.59, p < 0.001). After a multivariable analysis, MAGGIC score [odds ratio (OR): 3.92, p < 0.001], sodium (OR: 0.92, p = 0.003), N terminal pro B type natriuretic peptide (OR: 1.78, p = 0.009), hs troponin (OR: 1.28, p = 0.044), MRA (OR: 0.61, p = 0.019) and furosemide dose (OR: 1.03, p = 0.001) were found to be independent predictors of CRS development. The MAGGIC score was associated with CRS development (area under curve = 0.778). The MAGGIC score may be associated with CRS in HFrEF patients.

Predicting 1-Year Mortality in Outpatients With Heart Failure With Reduced Left Ventricular Ejection Fraction: Do Empiric Models Outperform Physician Intuitive Estimates? A Multicenter Cohort Study.

Many studies have demonstrated that physicians often err in estimating patient prognosis. No studies have directly compared physician to model predictive performance in heart failure (HF). We aimed to compare the accuracy of physician versus model predictions of 1-year mortality. This multicenter prospective cohort study on 11 HF clinics in 5 provinces in Canada included consecutive consented outpatients with HF with reduced left ventricular ejection fraction (<40%). By collecting clinical data, we calculated predicted 1-year mortality using the Seattle HF Model (SHFM), the Meta-Analysis Global Group in Chronic HF score, and the HF Meta-Score. HF cardiologists and family doctors, blinded to model predictions, estimated patient 1-year mortality. During 1-year follow-up, we recorded the composite end point of mortality, urgent ventricular assist device implant, or heart transplant. We compared physicians and model discrimination (C statistic), calibration (observed versus predicted event rate), and risk reclassification. The study included 1643 patients with ambulatory HF with a mean age of 65 years, 24% female, and mean left ventricular ejection fraction of 28%. Over 1-year follow-up, 9% had an event. The SHFM had the best discrimination (SHFM C statistic 0.76; HF Meta-Score 0.73; Meta-Analysis Global Group in Chronic Heart Failure 0.70) and calibration. Physicians' discrimination differed little (0.75 for HF cardiologists and 0.73 for family doctors) but both physician groups substantially overestimated risk by >10% in both low- and high-risk patients (poor calibration). In risk reclassification analysis, among patients without events, the SHFM better classified 51% in comparison to HF cardiologists and 43% in comparison to family doctors. In patients with events, the SHFM erroneously assigned lower risk to 44% in comparison to HF cardiologists and 34% in comparison to family doctors. Family doctors and HF cardiologists showed adequate risk discrimination, with however substantial overestimation of absolute risk. Predictive models showed higher accuracy. Incorporating models in family and HF cardiology practices may improve patient care and resource use in HF with reduced left ventricular ejection fraction. URL: https://www. gov; Unique identifier: NCT04009798.

Prognostic Value of 6-Minute Walk Test in Advanced Heart Failure With Reduced Ejection Fraction

There is limited evidence regarding the prognostic value of the 6-minute walk test for patients with advanced heart failure (HF). Accordingly, we studied 260 patients presenting to inpatient cardiac rehabilitation (CR) with advanced HF. The primary outcome was 3-year all-cause mortality after discharge from CR. The association between 6-minute walk distance (6MWD) and the primary outcome was determined using the multivariable Cox regression analysis. To avoid collinearity, 6MWD at admission (6MWDadm) to CR and 6MWD at discharge (6MWDdisch) from CR were analyzed separately. At multivariable analysis, 4 baseline characteristics (age, ejection fraction, systolic blood pressure, and blood urea nitrogen) were identified as prognostic of the primary outcome (baseline risk model). After adjusting for the baseline risk model, the hazard ratios of 6MWDadm and 6MWDdisch modeled as per 50-m increase for the primary outcome were 0.92 (95% confidence interval [CI] 0.85 to 0.99, p=0.035) and 0.93 (95% CI 0.88 to 0.99, p=-017), respectively. After adjusting for the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) score, the corresponding hazard ratios were 0.91 (95% CI 0.84 to 0.98, p=0.017) and 0.93 (95% CI 0.88 to 0.99, p=0.016). The addition of either 6MWDadm or 6MWDdisch to the baseline risk model or the MAGGIC score yielded a statistically significant increase in global chi-square and in the net proportion of survivors reclassified downward. In conclusion, our data suggest that the distance covered during a 6-minute walk test predicts survival and provides incremental prognostic information on the top of well-established prognostic factors and the MAGGIC risk score in advanced HF.

Prognostic significance of addition of electrocardiographic findings to the MAGGIC heart failure risk score

Abstract Funding Acknowledgements Type of funding sources: None. Main funding source(s): Researchers Background The Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) is a scoring system that is easy to use in outpatient or inpatient settings and was developed to predict the survival of heart failure (HF) patients after hospitalization. Aim This study aims to determine the prognostic significance of MAGGIC risk score combined with electrocardiography (ECG) parameters in decompensated patients with heart failure with reduced left ventricular ejection fraction (HFrEF) who were hospitalized for worsening HF. Methods A total of 562 HF patients with New York Heart Association (NYHA) II-IV functional class who were discharged after hospitalization for decompensated HF between 2013 and 2018 in a single center were included. MAGGIC risk scores of all participating patients were calculated according to baseline characteristics gathered using data from the initial hospitalization for HF. In addition, electrocardiographic findings of all patients were examined. Results During the follow-up period (4.5 ± 1.2 years) 177 patients died. MAGGIC scores were observed to be higher in non-survivors compared to surviving patients (28.69 ± 7.01 vs. 22.82 ± 6.05, p &amp;lt; 0.001). After a multivariate analysis, MAGGIC score (OR:1.090, p &amp;lt; 0.001), development of cardio-renal syndrome (OR:2.035, p &amp;lt; 0.001), presence of left bundle branch block (LBBB) (OR:1.931, p &amp;lt; 0.001), atrial fibrillation (AF) (OR:1.817, p &amp;lt; 0.001), and fragmented QRS (fQRS) (OR:1.671, p = 0.002) on ECG were found to be independent predictors of mortality. While the MAGGIC score was shown to predict mortality (AUC = 0.739), its predictive power was improved when combined with AF (AUC = 0.752), LBBB (AUC = 0.745), and fQRS (AUC = 0.757) respectively, as well as in the combined final model (MAGGIC score, AF, LBBB, fQRS) (AUC = 0.787). Conclusions Our findings showed that addition of electrocardiographic findings to the MAGGIC heart failure risk score has prognostic significance in decompensated patients with HFrEF.

Abstract P177: Circulating Ketone Bodies and Mortality in Heart Failure: A Community Cohort Study

Background: Heart failure (HF) is associated with metabolic alterations, including ketogenesis. However, determinants of ketogenesis and risk of mortality in HF is not defined. Total ketone bodies (KB) include β-hydroxybutyrate, acetoacetate, and acetone and can be measured in plasma by nuclear magnetic resonance (NMR). The aim of this study is to determine the relationship between KB and clinical characteristics in a community HF cohort and to assess the association between KB and all-cause mortality. Methods: A population-based cohort of 1,389 HF patients was prospectively enrolled between 2003 and 2012. Plasma KB was measured by LP4 NMR LipoProfile ® assay/test on the Vantera® NMR analyzer platform. A conditional inference tree method (ctree R Package) was used to determine optimal KB group cut points. Associations between clinical characteristics and KB were measured with Wilcoxon rank sum test and Pearson’s Chi-squared test. Kaplan-Meier method estimated survival. Cox regression analyses were used to estimate associations between KB concentrations and mortality. Results: Among the 1,382 HF patients with KB measurements, the median age was 78 years (IQR 68-84) and 52% were men. Median KB was 180 μM (IQR 134-308). Patients were divided into two groups with lower KB (≤471.5 μM) and higher KB (&gt;471.5 μM). Patients with higher KB (N=210) had lower BMI, higher BNP, and were more likely to be in the New York Heart Association class III-IV; however, these patients were less likely to have hyperlipidemia, coronary disease, or diabetes mellitus (P &lt; 0.05). Age, sex, creatinine, ejection fraction, or Meta-Analysis Global Group in Chronic HF (MAGGIC) score did not differ by KB group. Higher KB was associated with worse survival (figure). After adjustment for the MAGGIC score, higher KB was associated with increased risk of mortality (HR 1.3; 95% CI, 1.08-1.48). Conclusions: In this community HF cohort, higher KB was associated with increased mortality, independent of the MAGGIC score.

Abstract P178: Incremental Value of Charlson Comorbidity Index Over Disease-Centric Score in Heart Failure

Introduction: Heart Failure (HF) is a syndrome of high comorbidity and mortality. The impact of comorbidities on life expectancy in HF is well studied, but guideline-recommended disease-centric risk scores such as the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) score may not fully account for the effect of comorbidities. The Charlson Comorbidity Index (Charlson) is a validated measure that quantifies the prognostic impact of comorbidities. Objective: To examine the incremental value of Charlson over MAGGIC in predicting death in HF. Methods: In a population-based HF cohort, we computed MAGGIC and Charlson scores using electronically linked medical records. Patients were divided based on ejection fraction (EF) into reduced [EF &lt;50%, HFrEF] or preserved [EF ≥50%, HFpEF]. Cox regression was performed to assess the association between the risk scores and mortality. The incremental value of Charlson over MAGGIC was tested by calculating the area under the ROC [receiver operating characteristic] curves (AUCs) with 95% confidence interval (CI). Results: We studied 1,388 patients with HF validated using the Framingham criteria (mean age, 75±13 years, 48% female, mean EF, 49±17%). The median Charlson was 7.0 (interquartile range 5.0-9.0) and was higher in HFpEF than HFrEF (7.0 [5.0-9.0] vs. 6.0 [4.0-8.3] respectively. Over a median follow-up of 13.9 years (13.3-14.2), mortality was 17.4% (95% CI, 15.4 -19.3%) and 36.8% (95% CI, 34.2-39.3%) at 1, and 3 years respectively. In regression analysis, increasing MAGGIC and Charlson were independently associated with death (HR 1.09, 95% CI 1.08-1.11 and HR,1.22, 95% CI 1.20-1.24, both p &lt;0.001) irrespective of EF. Discrimination ability was improved by adding Charlson over MAGGIC (Table), reaching statistical significance at 3 years. Conclusion: In this HF cohort, the Charlson index provided an added value over MAGGIC in predicting the risk of death at 3 years. These findings emphasize the importance of accounting for comorbidities in mid-term risk stratification in HF.