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Background Heart failure (HF) is a prevalent and deadly disease, and preventive strategies focused on at-risk individuals are needed. Current HF prediction models have not examined HF subtypes. We sought to develop and validate risk prediction models for HF with preserved and reduced ejection fraction (HFpEF, HFrEF). Methods and Results Of 28,820 participants from four community-based cohorts, 982 developed incident HFpEF and 909 HFrEF during a median follow-up of 12 years. Three cohorts were combined and a 2:1 random split used for derivation and internal validation, with the fourth cohort as external validation. Models accounted for multiple competing risks (death, other HF subtype, unclassified HF). The HFpEF-specific model included age, sex, systolic blood pressure, body mass index, antihypertensive treatment, and prior myocardial infarction; it had good discrimination in derivation (c-statistic 0.80, 95% CI 0.78–0.82) and validation samples (internal 0.79, 95% CI 0.77–0.82; external 0.76, 95% CI 0.71–0.80). The HFrEF-specific model additionally included smoking, left ventricular hypertrophy (LVH), left bundle branch block (LBBB), and diabetes; it had good discrimination in derivation (c-statistic 0.82, 95% CI 0.80–0.84) and validation samples (internal 0.80, 95% CI 0.78–0.83; external 0.76, 95% CI 0.71–0.80). Age was more strongly associated with HFpEF, and male sex, LVH, LBBB, prior myocardial infarction, and smoking with HFrEF (P for each comparison ≤ 0.02). Conclusions We describe and validate risk prediction models for HF subtypes, and show good discrimination in a large sample. Some risk factors differed between HFpEF and HFrEF, supporting the notion of pathogenetic differences among HF subtypes.

AimsGrowth differentiation factor 15 (GDF15), ST2, high-sensitivity troponin T (hsTnT), and N-terminal pro brain natriuretic peptide (NT-proBNP) are biomarkers of distinct mechanisms that may contribute to the pathophysiology of heart failure (HF) [inflammation (GDF15); ventricular remodelling (ST2); myonecrosis (hsTnT); and wall stress (NT-proBNP)]. Methods and resultsWe compared circulating levels of GDF15, ST2, hsTnT, and NT-proBNP, as well as their combinations, in compensated patients with clinical HF with reduced ejection fraction (HFREF) (n ¼ 51), HF with preserved ejection fraction (HFPEF) (n¼ 50), and community-based controls (n ¼ 50). Compared with controls, patients with HFPEF and HFREF had higher median levels of GDF15 (540 pg/mL vs. 2529 and 2672 pg/mL, respectively), hsTnT (3.7 pg/mL vs. 23.7 and 35.6 pg/mL), and NT-proBNP (69 pg/mL vs. 942 and 2562 pg/mL), but not ST2 (27.6 ng/mL vs. 31.5 and 35.3 ng/mL), adjusting for clinical covariates. In receiver operating characteristic curve analyses, NT-proBNP distinguished HFREF from controls with an area under the curve (AUC) of 0.987 (P , 0.001); GDF15 distinguished HFPEF from controls with an AUC of 0.936 (P , 0.001); and the combination of NT-proBNP and GDF15 distinguished HFPEF from controls with an AUC of 0.956 (P , 0.001). NT-proBNP and hsTnT levels were higher in HFREF than in HFPEF (adjusted P , 0.04). The NT-proBNP:GDF15 ratio distinguished between HFPEF and HFREF with the largest AUC (0.709; P , 0.001). ConclusionsOur study provides comparative data on physiologically distinct circulating biomarkers in HFPEF, HFREF, and controls from the same community. These data suggest a prominent role for myocardial injury (hsTnT) with increased wall stress (NT-proBNP) in HFREF, and systemic inflammation (GDF15) in HFPEF.Heart failure with preserved ejection fraction † ST2 † Growth differentiation factor 15 † High-sensitivity troponin T † N-terminal pro brain natriuretic peptide † These authors contributed equally to the study.

Background Atrial fibrillation (AF) and heart failure (HF) frequently coexist and together confer an adverse prognosis. The association of AF with HF subtypes has not been well-described. We sought to examine differences in the temporal association of AF and HF with preserved versus reduced ejection fraction (HFpEF vs HFrEF). Methods and Results We studied Framingham Heart Study participants with new-onset AF and/or HF between 1980–2012. Among 1737 individuals with new AF, (mean-age 75±12, 48% women) more than one third (37%) had HF. Conversely among 1166 individuals with new HF (mean-age 79±11, 53% women), more than half (57%) had AF. Prevalent AF was more strongly associated with incident HFpEF (multivariable-adjusted hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.48–3.70, no AF as referent) vs HFrEF (HR 1.32, 95%CI 0.83–2.10), with a trend toward difference between HF subtypes (P for difference 0.06). Prevalent HF was associated with incident AF (HR 2.18, 95%CI 1.26–3.76, no HF as referent). The presence of both AF and HF portended greater mortality risk compared with those without either condition, particularly among individuals with new HFrEF and prevalent AF (HR 2.72, 95%CI 2.12–3.48) compared with new HFpEF and prevalent AF (HR 1.83, 95%CI 1.41–2.37, P for difference 0.02). Conclusions AF occurs in more than half of individuals with HF, and HF in more than one third of individuals with AF. AF precedes and follows both HFpEF and HFrEF, with some differences in temporal association and prognosis. Future studies focused on underlying mechanisms of these dual conditions are warranted.