Aims To assess the proportion of patients with heart failure and reduced ejection fraction (HFrEF) who are eligible for sacubitril/valsartan (LCZ696) based on the European Medicines Agency/Food and Drug Administration (EMA/FDA) label, the PARADIGM‐HF trial and the 2016 ESC guidelines, and the association between eligibility and outcomes. Methods and results Outpatients with HFrEF in the ESC‐EORP‐HFA Long‐Term Heart Failure (HF‐LT) Registry between March 2011 and November 2013 were considered. Criteria for LCZ696 based on EMA/FDA label, PARADIGM‐HF and ESC guidelines were applied. Of 5443 patients, 2197 and 2373 had complete information for trial and guideline eligibility assessment, and 84%, 12% and 12% met EMA/FDA label, PARADIGM‐HF and guideline criteria, respectively. Absent PARADIGM‐HF criteria were low natriuretic peptides (21%), hyperkalemia (4%), hypotension (7%) and sub‐optimal pharmacotherapy (74%); absent Guidelines criteria were LVEF>35% (23%), insufficient NP levels (30%) and sub‐optimal pharmacotherapy (82%); absent label criteria were absence of symptoms (New York Heart Association class I). When a daily requirement of ACEi/ARB ≥ 10 mg enalapril (instead of ≥ 20 mg) was used, eligibility rose from 12% to 28% based on both PARADIGM‐HF and guidelines. One‐year heart failure hospitalization was higher (12% and 17% vs. 12%) and all‐cause mortality lower (5.3% and 6.5% vs. 7.7%) in registry eligible patients compared to the enalapril arm of PARADIGM‐HF. Conclusions Among outpatients with HFrEF in the ESC‐EORP‐HFA HF‐LT Registry, 84% met label criteria, while only 12% and 28% met PARADIGM‐HF and guideline criteria for LCZ696 if requiring ≥ 20 mg and ≥ 10 mg enalapril, respectively. Registry patients eligible for LCZ696 had greater heart failure hospitalization but lower mortality rates than the PARADIGM‐HF enalapril group.

With careful donor and recipient selection, adults with end-stage CHD undergoing HT can achieve excellent early and midterm survival, comparable to the survival of patients who undergo transplantation for other diagnoses.

Serial measurement of BNP in outpatients with LVAD correlates with the occurrence of adverse events. Assessment of absolute values of BNP peak seems to have a similar accuracy to analysis of intra-individual variation of BNP and it is more practical.

Aims Diabetes mellitus, chronic obstructive pulmonary disease, and chronic kidney disease are prevalent in patients with heart failure with reduced ejection fraction (HFrEF). We have analysed the impact of co-morbidities on quality of life (QoL) and outcome. Methods and results A total of 397 patients (58.8 ± 11.0 years, 73.6% with New York Heart Association functional class ≥3) with stable advanced HFrEF were followed for a median of 1106 (inter-quartile range 379-2606) days, and 68% of patients (270 patients) experienced an adverse outcome (death, urgent heart transplantation, and implantation of mechanical circulatory support). Chronic obstructive pulmonary disease was present in 16.4%, diabetes mellitus in 44.3%, and chronic kidney disease in 34.5% of patients; 33.5% of patients had none, 40.0% had one, 21.9% had two, and 3.8% of patient had three co-morbidities. Patients with more co-morbidities reported similar QoL (assessed by Minnesota Living with Heart Failure Questionnaire, 45.46 ± 22.21/49.07 ± 21.69/47.52 ± 23.54/46.77 ± 23.60 in patients with zero to three co-morbidities, P for trend = 0.51). Multivariable regression analysis revealed that furosemide daily dose, systolic blood pressure, New York Heart Association functional class, and body mass index, but not the number of co-morbidities, were significantly (P < 0.05) associated with QoL. Increasing co-morbidity burden was associated with worse survival (P < 0.0001), lower degree of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment (P = 0.001), and increasing levels of BNP (mean of 685, 912, 1053, and 985 ng/L for patients with zero to three co-morbidities, P for trend = 0.008) and cardiac troponin (sm-cTnI, P for trend = 0.0496), which remained significant (P < 0.05) after the adjustment for left ventricular ejection fraction, left ventricular end-diastolic diameter, right ventricular dysfunction grade, body mass index, and estimated glomerular filtration rate. Conclusions In stable advanced HFrEF patients, co-morbidities are not associated with impaired QoL, but negatively affect the prognosis both directly and indirectly through lower level of HF pharmacotherapy and increased myocardial stress and injury.

The role of metformin (MET) in the treatment of patients with advanced HFrEF and type 2 diabetes mellitus (DM) is not firmly established. We studied the impact of MET on metabolic profile, quality of life (QoL) and survival in these patients. A total of 847 stable patients with advanced HFrEF (57.4 ± 11.3 years, 67.7% NYHA III/IV, LVEF 23.6 ± 5.8%) underwent clinical and laboratory evaluation and were prospectively followed for a median of 1126 (IQRs 410; 1781) days for occurrence of death, urgent heart transplantation or mechanical circulatory support implantation. A subgroup of 380 patients (44.9%) had DM, 87 of DM patients (22.9%) were treated with MET. Despite worse insulin sensitivity and more severe DM (higher BMI, HbA1c, worse insulin resistance), MET-treated patients exhibited more stable HF marked by lower BNP level (400 vs. 642 ng/l), better LV and RV function, lower mitral and tricuspid regurgitation severity, were using smaller doses of diuretics (all p < 0.05). Further, they had higher eGFR (69.23 vs. 63.34 ml/min/1.73 m2) and better QoL (MLHFQ: 36 vs. 48 points, p = 0.002). Compared to diabetics treated with other glucose-lowering agents, MET-treated patients had better event-free survival even after adjustment for BNP, BMI and eGFR (p = 0.035). Propensity score-matched analysis with 17 covariates yielded 81 pairs of patients and showed a significantly better survival for MET-treated subgroup (p = 0.01). MET treatment in patients with advanced HFrEF and DM is associated with improved outcome by mechanisms beyond the improvement of blood glucose control.