Associations With and Prognostic and Discriminatory Role of N-Terminal Pro-B-Type Natriuretic Peptide in Heart Failure With Preserved Versus Mid-range Versus Reduced Ejection Fraction.
The aim of this study was to characterize N-terminal pro-B-type natriuretic peptide (NT-proBNP) in terms of determinants of levels and of its prognostic and discriminatory role in heart failure with mid-range (HFmrEF) versus preserved (HFpEF) and reduced (HFrEF) ejection fraction.
In 9847 outpatients with HFpEF (n = 1811; 18%), HFmrEF (n = 2122; 22%) and HFrEF (n = 5914; 60%) enrolled in the Swedish Heart Failure Registry, median NT-proBNP levels were 1428, 1540, and 2288 pg/mL, respectively. Many determinants of NT-proBNP differed by ejection fraction, with atrial fibrillation (AF) more important in HFmrEF and HFpEF, diabetes and hypertension in HFmrEF, and age and body mass index in HFrEF and HFmrEF, whereas renal function, New York Heart Association functional class, heart rate, and anemia were similar. Hazard ratios for death and death/HF hospitalization for NT-proBNP above the median ranged from 1.48 to 2.00 and were greatest for HFmrEF and HFpEF. Areas under the receiver operating characteristic curve for death and death/HF hospitalization were greater in HFmrEF than in HFpEF and HFrEF and were reduced by AF in HFpEF and HFmrEF but not in HFrEF.
In HFpEF and especially HFmrEF, NT-proBNP was more prognostic and discriminatory, but also more affected by confounders such as AF. These data support the use of NT-proBNP for eligibility, enrichment, and surrogate end points in HFpEF and HFmrEF trials, and suggest that cutoff levels for eligibility should be carefully tailored to comorbidity.
Savarese G
，Orsini N
，Hage C
，Dahlström U
，Vedin O
，Rosano GMC
，Lund LH
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Bio-profiling and bio-prognostication of chronic heart failure with mid-range ejection fraction.
Recent ESC guidelines on heart failure (HF) have introduced a new phenotype based on left ventricular ejection fraction (LVEF), called the mid-range (HFmrEF). This phenotype falls between the classical reduced (HFrEF) and preserved (HFpEF) HF phenotypes. We aimed to characterize the HFmrEF biomarker profile and outcomes.
1069 consecutive ambulatory patients were included in the study (age 66.2 ± 12.8 years); 800 with HFrEF (74.8%), 134 with HFmrEF (12.5%), and 135 with HFpEF (12.5%). We measured serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), soluble suppression of tumorigenicity (ST2), galectin-3, high-sensitivity C-reactive protein, cystatin-C, neprilysin, and soluble transferrin receptor, during 4.9 ± 2.8 years of follow-up. The primary end-point was the composite: cardiovascular death or HF-related hospitalization. We also examined all-cause, cardiovascular death, and the composite: all-cause death or HF-related hospitalization.
NTproBNP levels in HFmrEF were similar to levels in HFpEF, but significantly lower than levels in HFrEF. No other studied biomarkers were different between HFmrEF and HFrEF. All biomarkers, except neprilysin, showed higher risk prediction capabilities in HFmrEF than in HFrEF or HFpEF. The largest difference between HFrEF and HFmrEF was the hs-TnT level (hazard ratio [HR]: 4.72, 95% CI: 2.81-7.94 vs. HR: 1.67, 95%CI: 1.74-1.89; all p < 0.001).
Although HFmrEF is acknowledged as an intermediate phenotype between HFrEF and HFpEF, from a multi-biomarker point of view, HFmrEF was similar to HFrEF, except that NTproBNP levels were lower. Biomarkers commonly used for HFrEF risk prediction are more valuable for HFmrEF risk stratification.
Moliner P
，Lupón J
，Barallat J
，de Antonio M
，Domingo M
，Núñez J
，Zamora E
，Galán A
，Santesmases J
，Pastor C
，Bayes-Genis A
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Atrial Fibrillation in Heart Failure With Preserved, Mid-Range, and Reduced Ejection Fraction.
The study sought to assess the independent risk factors for, consequences of, and outcomes with atrial fibrillation (AF) compared with sinus rhythm (SR) in heart failure (HF) with preserved ejection fraction (HFpEF) versus HF with mid-range ejection fraction (HFmrEF) versus HF with reduced ejection fraction (HFrEF).
AF is common in HF, but most data are from HFrEF. The importance of AF in HFpEF and HFmrEF is less well known.
In patients from 2000 to 2012 in the SwedeHF (Swedish Heart Failure Registry) registry, enriched with patient-level data from national health care registries, the authors assessed prevalence of, associations with, and prognostic impact of AF in HFpEF versus HFmrEF versus HFrEF.
Of 41,446 patients, 23% had HFpEF, 22% had HFmrEF, and 55% had HFrEF. The prevalence of AF was 65%, 60%, and 53% in HFpEF, HFmrEF, and HFrEF, respectively. Independent associations with AF were similar in HFpEF, HFmrEF, and HFrEF and included greater age, male, duration of HF, prior myocardial infarction, and prior stroke or transient ischemic attack (TIA). The adjusted hazard ratios for AF versus SR in HFpEF, HFmrEF, and HFrEF were the following: for death, 1.11 (95% confidence interval [CI]: 1.02 to 1.21), 1.22 (95% CI: 1.12 to 1.33), and 1.17 (95% CI: 1.11 to 1.23); for HF hospitalization or death, 1.17 (95% CI: 1.09 to 1.26), 1.29 (95% CI: 1.20 to 1.40), and 1.15 (95% CI: 1.10 to 1.20); and for stroke or TIA or death, 1.15 (95% CI: 1.07 to 1.25), 1.23 (95% CI: 1.13 to 1.34), and 1.19 (95% CI: 1.14 to 1.26).
AF was progressively more common with increasing ejection fraction, but was associated with similar clinical characteristics in HFpEF, HFmrEF, and HFrEF. AF was associated with similarly increased risk of death, HF hospitalization, and stroke or TIA in all ejection fraction groups. In contrast, AF and SR populations were considerably different regarding associated patient characteristics and outcomes.
Sartipy U
，Dahlström U
，Fu M
，Lund LH
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Reductions in N-Terminal Pro-Brain Natriuretic Peptide Levels Are Associated With Lower Mortality and Heart Failure Hospitalization Rates in Patients With Heart Failure With Mid-Range and Preserved Ejection Fraction.
In heart failure with mid-range ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF), feasible surrogate end points are needed for phase II trials. The aim was to assess whether a reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with improved mortality/morbidity in an unselected population of HFmrEF and HFpEF patients.
In the Swedish Heart Failure Registry, HFmrEF (EF=40%-49%) and HFpEF (EF≥50%) patients reporting at least 2 consecutive outpatient NT-proBNP assessments were prospectively studied. Associations between reduction in NT-proBNP and overall mortality, HF hospitalization, and their composite were assessed by multivariable Cox regressions, with NT-proBNP changes modeled as binary (decrease/increase) or quantitative predictor by restricted cubic splines. In 650 patients, at a median of 7 months between the 2 measurements of NT-proBNP and over a median follow-up of 1.65 years, 361 patients (55%) showed a reduction and 289 patients (45%) an increase in NT-proBNP. Change in NT-proBNP was associated with risk of outcomes. Fifty-seven patients (16%) who decreased their NT-proBNP versus 78 patients (27%) who increased it died from any cause (adjusted hazard ratio=0.53; 95% confidence interval=0.36-0.77), 61 (17%) versus 86 (30%) were hospitalized for HF (hazard ratio=0.41; 95% confidence interval=0.29-0.60), and 96 (27%) versus 125 (43%) reported the composite outcome (hazard ratio=0.46; 95% confidence interval=0.34-0.62). These findings were replicated in HFmrEF and HFpEF separately.
In HFmrEF and HFpEF during routine care, decreases in NT-proBNP were associated with improved mortality and morbidity. Studies to determine whether NT-proBNP changes in response to therapy predict drug efficacy are needed.
Savarese G
，Hage C
，Orsini N
，Dahlström U
，Perrone-Filardi P
，Rosano GM
，Lund LH
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