Aims Galectin‐3 is a marker of myocardial fibrosis and mediates aldosterone‐induced cardiovascular inflammation and fibrosis. Characteristics of galectin‐3 and its response to spironolactone have not been evaluated in heart failure with preserved ejection fraction (HFpEF). The aim of this study was to determine the association between galectin‐3 levels and patient characteristics in HFpEF; to evaluate the interaction between spironolactone and galectin‐3 levels; and to assess the association between galectin‐3 and clinical outcomes. Methods and results Aldo‐DHF investigated spironolactone 25 mg once daily vs. placebo for 12 months in patients with NYHA class II–III, LVEF ≥50%, grade ≥ I diastolic dysfunction, and peakVO2 ≤ 25 mL/kg/min. Galectin‐3 levels were obtained at baseline, and at 6 and 12 months. The association between baseline galectin‐3, change in galectin‐3, and all‐cause death or hospitalization was evaluated, and the interaction between galectin‐3 and treatment was assessed. Median baseline galectin‐3 was 12.1 ng/mL. After multivariable adjustment, baseline galectin‐3 inversely correlated with peak VO2 (P = 0.021), 6 min walk distance (P = 0.002), and Short Form 36 (SF‐36) physical functioning (P = 0.001), and directly correlated with NYHA class (P = 0.007). Baseline NT‐proBNP correlated with E/e' velocity ratio (P ≤ 0.001), left atrial volume index (P < 0.001), and LV mass index (P = 0.009). Increasing galectin‐3 at 6 or 12 months was associated with all‐cause death or hospitalization independent of treatment arm [hazard ratio (HR) 3.319, 95% confidence interval (CI) 1.214–9.07, P = 0.019] and NT‐proBNP (HR 3.127, 95% CI 1.144–8.549, P = 0.026). Spironolactone did not influence galectin‐3 levels. Conclusion Galectin‐3 levels are modestly elevated in patients with stable HFpEF and relate to functional performance and quality of life. Increasing galectin‐3 was associated with worse outcome, independent of treatment or NT‐proBNP.

In patients with HFpEF, exercise training improved emotional status, physical and social dimensions of QoL as well as symptoms of depression from pre to post test. Physical dimensions of QoL and general health perception also improved significantly with exercise in comparison to usual care.

Heart failure with preserved ejection fraction (HFpEF) is a common disease with high incidence and increasing prevalence. Patients suffer from functional limitation, poor health-related quality of life, and reduced prognosis. A pilot study in a smaller group of HFpEF patients showed that structured, supervised exercise training (ET) improves maximal exercise capacity, diastolic function, and physical quality of life. However, the long-term effects of ET on patient-related outcomes remain unclear in HFpEF. The primary objective of the Exercise training in Diastolic Heart Failure (Ex-DHF) trial is to investigate whether a 12 month supervised ET can improve a clinically meaningful composite outcome score in HFpEF patients. Components of the outcome score are all-cause mortality, hospitalizations, NYHA functional class, global self-rated health, maximal exercise capacity, and diastolic function. After undergoing baseline assessments to determine whether ET can be performed safely, 320 patients at 11 trial sites with stable HFpEF are randomized 1:1 to supervised ET in addition to usual care or to usual care alone. Patients randomized to ET perform supervised endurance/resistance ET (3 times/week at a certified training centre) for 12 months. At baseline and during follow-up, anthropometry, echocardiography, cardiopulmonary exercise testing, and health-related quality of life evaluation are performed. Blood samples are collected to examine various biomarkers. Overall physical activity, training sessions, and adherence are monitored and documented throughout the study using patient diaries, heart rate monitors, and accelerometers. The Ex-DHF trial is the first multicentre trial to assess the long-term effects of a supervised ET programme on different outcome measures in patients with HFpEF.

Left ventricular filling pressure (LVFP) is a marker for diastolic dysfunction and heart failure (HF) with preserved ejection fraction (pEF). The interaction between arterial stiffness (AS) and elevated LVFP has not been sufficiently investigated. In 257 patients with preserved left ventricular ejection fraction (mean age: 66 years, 53% female, mean left ventricular ejection fraction: 61%) and at least one cardiovascular risk factor (eg, hypertension and diabetes) for the development of HF or a previous diagnosis of HF, LVFP was estimated in accordance with the recommendations of the American Society of Echocardiography (elevated when E/e' ≥ 13, left atrial volume index ≥ 34 mL/m). LVFP was correlated with radial pulse wave analysis (augmentation index normalized by 75 b/min [AIx@75]) and carotid-femoral pulse wave velocity (cfPWV). Thirty-eight percent of patients demonstrated an elevated LVFP. These patients were significantly older (68.3 ± 7.4 vs. 63.5 ± 7.6 years, P < .001), demonstrated a higher body mass index (29.8 ± 4.6 vs. 28.0 ± 5.0; P < .01), presented more often with hypertension (89.7% vs. 73.1%, P < .01), hypercholesterolemia (32.0% vs. 21.3%, P < .05), dyspnea on exertion (28.4% vs. 16.6%, P < .05), and peripheral edema (25.3% vs. 10.2%, P < .01). cfPWV and AIx@75 and were significantly elevated in patients with elevated LVFP (12.2 ± 2.7 m/s vs. 10.5 ± 2.6 m/s, P < .001, an 29.2 ± 6.7% vs. 27.4 ± 6.7%, P < .05 respectively). cfPWV and AIx@75 were correlated with echocardiographic parameters, that is, posterior wall thickness (r = 0.292, P < .001; r = 0.167, P < .01), left ventricular mass index (r = 0.255, P < .001; r = -0.192, P < .01), e' (r = -0.508, P < .001; r = -0.159, P < .05), and E/e' (r = 0.380, P < .001; r = 0.200, P < .01). cfPWV correlated with left atrial volume index (r = 0.189, P < .05) and increasing E/A ratio (r = -0.334, P < .001). Multivariate linear regression analysis demonstrated age and PWV as most important and independent predictors of LVFP elevation in the cohort. Increased AS measured by cfPWV was associated with an elevated LVFP in patients with preserved systolic function. Whether targeting AS as a major component of diastolic dysfunction and HF with preserved ejection fraction needs to be further investigated.