Australian New Zealand Clinical Trial Registry (ACTRN12610000374066).

Right ventricular dysfunction is present in HFpEF and is even more pronounced in HFrEF for any given degree of pulmonary hypertension. It is independently predicted by left ventricular dysfunction but not by PASP. Right ventricular-arterial coupling is prognostically important in HF regardless of LVEF.

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.

Aim Growth differentiation factor 15 (GDF15) is a cytokine highly expressed in states of inflammatory stress. We aimed to study the clinical correlates and prognostic significance of plasma GDF15 in heart failure with preserved ejection fraction (HFpEF) vs. reduced ejection fraction(HFrEF), compared with N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), an indicator of haemodynamic wall stress. Methods Plasma GDF15 and NT‐proBNP were prospectively measured in 916 consecutive patients with HFrEF (EF <50%; n = 730) and HFpEF (EF ≥50%; n = 186), and measured again at 6 months in 488 patients. Patients were followed up for a composite outcome of death or first HF rehospitalization. Results Median GDF15baseline values were similarly elevated in HFpEF [2862 (1812 represent the 25th percentile and 4176 represent the 75th percentile) ng/L] and HFrEF [2517 (1555, 4030) ng/L] (P = 0.184), whereas NT‐proBNP was significantly lower in HFpEF than HFrEF (1119 ng/L vs. 2335 ng/L, P < 0.001). Independent correlates of GDF15baseline were age, systolic blood pressure, New York Heart Association (NYHA) class, diabetes, atrial fibrillation, sodium, haemoglobin, creatinine, diuretic therapy, high sensitivity troponin T (hsTnT) and NT‐proBNP (all P < 0.05). During a median follow‐up of 23 months, there were 379 events (307 HFrEF, 72 HFpEF). GDF15 remained a significant independent predictor for composite outcome even after adjusting for important clinical predictors including hsTnT and NT‐proBNP (adjusted hazard ratio 1.76 per 1 Ln U, 95% confidence interval 1.39–2.21; P < 0.001), regardless of HF group (Pinteraction = 0.275). GDF15baseline provided incremental prognostic value when added to clinical predictors, hsTnT and NT‐proBNP (area under receiver operating characteristic curve increased from 0.720 to 0.740, P < 0.019), with a net reclassification improvement of 0.183 (P = 0.004). Patients with ≥20% GDF156months increase had higher risk for composite outcome (adjusted hazard ratio 1.68, 95% confidence interval 1.15–2.45; P = 0.007) compared with those with GDF156months within ± 20% of baseline. Conclusions The similarly elevated levels and independent prognostic utility of GDF15 in HFrEF and HFpEF suggest that beyond haemodynamic stress (NT‐proBNP), inflammatory injury (GDF15) may play an important role in both HF syndromes.

AimsCurrent heart failure (HF) guidelines highlight the importance of iron deficiency (ID) in HF. Whether HF itself or age-related comorbidities contribute to ID is uncertain, and previous data were limited to Western populations. We aimed to study the prevalence, clinical correlates, functional significance and prognosis of ID in HF patients, compared with community-based controls in a multi-ethnic Southeast Asian population. Methods and resultsIron status was assessed in 751 HF patients (age 62.0 ± 12.2 years, 75.5% men, 64.7% Chinese, 23.9% Malay, 10.2% Indian) and 601 controls (age 56.9 ± 10.4 years, 49.8% men, 70.9% Chinese, 21.5% Malay, 7.2% Indian). ID, defined as ferritin <100 μg/L or ferritin 100-300 μg/L and transferrin saturation (Tsat) <20%, was present in 39.3% of controls and 61.4% of HF [odds ratio (OR) 3.5, 95% confidence interval (CI) 2.5-4.9, adjusting for clinical covariates]. Independent correlates of ID in HF were Indian ethnicity (OR 2.4 vs. Chinese, 95% CI 1.2-5.0), female gender (OR 2.8, 95% CI 1.7-4.8), larger body mass index (OR 1.05/unit increase, 95% CI 1.01-1.1) and decreased left ventricular ejection fraction (OR 1.03/unit decrease, 95% CI 1.01-1.04). In a subset of 48 HF patients undergoing cardiopulmonary exercise testing, Tsat correlated with peak oxygen consumption ( = 0.53, P < 0.01), independent of baseline characteristics. The HF patients with Tsat <20% as well as anaemia showed the poorest event-free survival after adjusting for clinical covariates.