Dataset Information

Plasma Proteomic Profile Predicts Survival in Heart Failure With Reduced Ejection Fraction.

ABSTRACT:

Background

It remains unclear whether the plasma proteome adds value to established predictors in heart failure (HF) with reduced ejection fraction (HFrEF). We sought to derive and validate a plasma proteomic risk score (PRS) for survival in patients with HFrEF (HFrEF-PRS).

Methods

Patients meeting Framingham criteria for HF with EF<50% were enrolled (N=1017) and plasma underwent SOMAscan profiling (4453 targets). Patients were randomly divided 2:1 into derivation and validation cohorts. The HFrEF-PRS was derived using Cox regression of all-cause mortality adjusted for clinical score and NT-proBNP (N-terminal pro-B-type natriuretic peptide), then was tested in the validation cohort. Risk stratification improvement was evaluated by C statistic, integrated discrimination index, continuous net reclassification index, and median improvement in risk score for 1-year and 3-year mortality.

Results

Participants' mean age was 68 years, 48% identified as Black, 35% were female, and 296 deaths occurred. In derivation (n=681), 128 proteins associated with mortality, 8 comprising the optimized HFrEF-PRS. In validation (n=336) the HFrEF-PRS associated with mortality (hazard ratio, 2.27 [95% CI, 1.84-2.82], P=6.3×10^-14), Kaplan-Meier curves differed significantly between HFrEF-PRS quartiles (P=2.2×10^-6), and it remained significant after adjustment for clinical score and NT-proBNP (hazard ratio, 1.37 [95% CI, 1.05-1.79], P=0.021). The HFrEF-PRS improved metrics of risk stratification (C statistic change, 0.009, P=0.612; integrated discrimination index, 0.041, P=0.010; net reclassification index=0.391, P=0.078; median improvement in risk score=0.039, P=0.016) and associated with cardiovascular death and HF phenotypes (eg, 6-minute walk distance, EF change). Most HFrEF-PRS proteins had little known connection to HFrEF.

Conclusions

A plasma multiprotein score improved risk stratification in patients with HFrEF and identified novel candidates.

SUBMITTER: Gui H

PROVIDER: S-EPMC8221080 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Plasma Proteomic Profile Predicts Survival in Heart Failure With Reduced Ejection Fraction.

Gui Hongsheng H She Ruicong R Luzum Jasmine J Li Jia J Bryson Timothy D TD Pinto Yigal Y Sabbah Hani N HN Williams L Keoki LK Lanfear David E DE

Circulation. Genomic and precision medicine 20210517 3

<h4>Background</h4>It remains unclear whether the plasma proteome adds value to established predictors in heart failure (HF) with reduced ejection fraction (HFrEF). We sought to derive and validate a plasma proteomic risk score (PRS) for survival in patients with HFrEF (HFrEF-PRS).<h4>Methods</h4>Patients meeting Framingham criteria for HF with EF<50% were enrolled (N=1017) and plasma underwent SOMAscan profiling (4453 targets). Patients were randomly divided 2:1 into derivation and validation c ...[more]

PMID: 33999650

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Project description:AimsThis study aimed to investigate the prognostic value of dynamic changes in left ventricular ejection fraction (EF) for cardiovascular (CV) outcomes in an all-comer heart failure (HF) population with reduced EF (HFrEF, EF < 40%). We sought to identify independent factors related to improvement in EF and to identify risk factors for increased risk of CV events in the subgroups of improved EF (iEF) and non-improved EF (niEF), respecively.Methods and resultsThis is a retrospective sub-analysis from the REDEAL HF trial, which included consecutive patients with chronic HF who were hospitalized from July 2009 to December 2017. Baseline and follow-up echocardiography data (interval ≥12 months) of 573 consecutive patients with HFrEF were analysed. iEF was defined as absolute improvement in EF ≥ 10% and follow-up EF over 40%. The primary endpoint was defined as a composite endpoint of cardiovascular (CV) death, CV hospitalization, or appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular arrhythmia. EF improved in 37.2% of patients with HFrEF during follow-up (median period of 17 months). iEF was independently associated with shorter HF duration (>4 vs. ≤4 years, odd ratio [OR] = 0.477, 95% CI 0.305-0.745), no coronary artery disease (CAD vs. no CAD, OR = 0.583, 95% CI 0.396-0.858), and no ICD implantation (ICD vs. no ICD, OR = 0.341, 95% CI 0.228-0.511). Compared with niEF, iEF was significantly and independently associated with lower all-cause mortality (22.1% vs. 31.1%, P = 0.019; hazard ratio [HR] = 0.674, 95% CI 0.469-0.968), lower CV mortality (8.9% vs. 16.1%, P = 0.015; HR = 0.539, 95% CI 0.317-0.916), and lower CV events risk (27.2% vs. 49.2%, P < 0.001; HR 0.519, 95% CI 0.381-0.708), after adjustment for age, sex, duration of HF, and other clinical risk factors. Hypertension (HR = 2.452, P = 0.032) and elevated N-terminal prohormone of brain natriuretic peptide (NT-proBNP >1153 pg/mL, HR = 4.372, P < 0.001) were identified as independent risk factors for CV events in the iEF subgroup. ICD implantation (HR = 1.533, P = 0.011), elevated NT-proBNP (HR = 1.626, P = 0.018), increased left atrial volume index (HR = 1.461, P = 0.021), reduced lateral mitral annular plane systolic excursion (HR = 1.478, P = 0.025), and reduced tricuspid plane systolic excursion (HR = 1.491, P = 0.039) were identified as risk factors for CV events in the niEF subgroup.ConclusionsImprovement in EF is independently related to the longer survival and lower CV related mortality and hospitalization rate of HFrEF. Elevated baseline NT-proBNP is identified as the strongest prognostic factor associated with increased CV events risk in HFrEF patients both with and without improved EF, regardless of age, sex, duration of HF, and other clinical risk factors.

Project description:AimsHeart failure with mildly reduced ejection fraction (HFmrEF) is associated with a favourable prognosis compared with heart failure (HF) with reduced ejection fraction (EF). We assessed whether left ventricular ejection fraction (LVEF) trajectory can be used to identify groups of patients with HFmrEF who have different clinical outcomes in a large retrospective study of patients with serial imaging.Methods and resultsPatients with HF and ≥2 echocardiograms performed ≥6 months apart were included if the LVEF measured 40-49% on the second study. Patients were classified as HFmrEF-Increasing if LVEF had increased ≥10% (n = 450), HFmrEF-Decreasing if LVEF had decreased ≥10% (n = 512), or HFmrEF-Stable if they did not meet other criteria (n = 389). The primary outcome was all-cause mortality or cardiovascular hospitalization after the second echocardiogram. Associations with time to first event were assessed with multivariable Cox analyses adjusted for age, co-morbidities, and medications. In total, 1351 patients with HFmrEF (median age 74, 64.2% male) were included with 28.8% exhibiting stable LVEF. During median follow-up of 15.3 months, the composite outcome occurred in 811 patients. During follow-up, patients with HFmrEF-Increasing were less likely to experience the primary outcome [adjusted hazard ratio (HR) 0.72, 95% confidence interval (CI) 0.60-0.88, P < 0.001] compared with HFmrEF-Stable. Patients with HFmrEF-Decreasing were more likely to experience the composite outcome in unadjusted analyses (unadjusted HR 1.19, 95% CI 1.01-1.40, P = 0.040) but not adjusted analyses (adjusted HR 1.16, 95% CI 0.98-1.37, P = 0.092). Associations with death or HF hospitalizations were similar (HFmrEF-Increasing: adjusted HR 0.72, 95% CI 0.59-0.88, P = 0.005; HFmrEF-Decreasing: adjusted HR 1.20, 95% CI 1.01-1.44, P = 0.044). Patients with HFmrEF-Decreasing had a similar risk of the composite outcome as patients with HF with reduced EF (adjusted HR 1.03, 95% CI 0.89-1.20, P = 0.670). Patients with HFmrEF-Increasing were less likely to experience the composite outcome compared with patients with HF with preserved EF (adjusted HR 0.73, 95% CI 0.62-0.87, P < 0.001).ConclusionsAmongst patients with HFmrEF, those exhibiting positive LVEF trajectory were less likely to experience adverse outcomes after correcting for important confounders including medical therapy. Categorizing HFmrEF patients based on LVEF trajectory provides meaningful clinical information and may assist clinicians with management decisions.

Project description:AimsThe relationship between diabetic microvascular complications and the incidence of two types of heart failure-heart failure with reduced ejection fraction (HFrEF) (left ventricular ejection fraction [LVEF] < 40%) and non-HFrEF (LVEF ≥ 40%)-in patients without prior heart failure has not been clarified. We herein examined the association between diabetic microvascular complications and HFrEF or non-HFrEF in patients with type 2 diabetes mellitus (T2DM) without prior heart failure.Methods and resultsIn this retrospective cohort study, we assessed the relationship between the presence of diabetic microvascular complications or severity of diabetic retinopathy (no apparent, non-proliferative and proliferative retinopathy) and nephropathy (normoalbuminuria, microalbuminuria, and macroalbuminuria) at baseline, with the primary outcome of first heart failure hospitalization classified as HFrEF or non-HFrEF in patients with type 2 diabetes mellitus without prior heart failure. Among 568 patients (69.2% males, mean age 66.2 ± 9.6 years), 70 experienced heart failure hospitalization (HFrEF: 24 and non-HFrEF: 46). Non-HFrEF hospitalization but not HFrEF hospitalization was significantly associated with the presence of diabetic microvascular complications. The incidence of non-HFrEF hospitalization was significantly higher in the proliferative retinopathy group than that in the no apparent retinopathy group (adjusted hazard ratio [HR] 2.96, 95% confidence interval [CI]: 1.09-6.83, P = 0.035) and in those with macroalbuminuria than in those with normoalbuminuria (adjusted HR 4.23, 95% CI: 2.24-7.85, P < 0.001) even after adjustment for age and sex. When non-HFrEF was classified into heart failure with mildly reduced ejection fraction (HFmrEF) (40% ≤ LVEF < 50%) and heart failure with preserved ejection fraction (HFpEF) (50% ≤ LVEF), HFmrEF and HFpEF hospitalizations were also found to be associated with the progression of retinopathy and nephropathy.ConclusionsIn patients with T2DM without prior heart failure, non-HFrEF hospitalization was more closely associated with the progression of diabetic microangiopathy than HFrEF. The development of non-HFrEF may be mediated through a mechanism similar to that of microvascular complications in these patients.

Dataset Information

Plasma Proteomic Profile Predicts Survival in Heart Failure With Reduced Ejection Fraction.

Background

Methods

Results

Conclusions

Publications

Plasma Proteomic Profile Predicts Survival in Heart Failure With Reduced Ejection Fraction.

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