In this document, we propose a universal definition of heart failure (HF) as a clinical syndrome with symptoms and/or signs caused by a structural and/or functional cardiac abnormality and corroborated by elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion. We also propose revised stages of HF as: At risk for HF (Stage A), Pre-HF (Stage B), Symptomatic HF (Stage C) and Advanced HF (Stage D). Finally, we propose a new and revised classification of HF according to left ventricular ejection fraction (LVEF). This includes HF with reduced ejection fraction (HFrEF): symptomatic HF with LVEF ≤40%; HF with mildly reduced ejection fraction (HFmrEF): symptomatic HF with LVEF 41-49%; HF with preserved ejection fraction (HFpEF): symptomatic HF with LVEF ≥50%; and HF with improved ejection fraction (HFimpEF): symptomatic HF with a baseline LVEF ≤40%, a ≥10 point increase from baseline LVEF, and a second measurement of LVEF > 40%.

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These data suggest that DWS, a simple index, is useful in assessing diastolic stiffness and that more advanced diastolic stiffness is associated with worse outcomes in HFpEF.

Endomyocardial biopsy (EMB) is an invasive procedure, globally most often used for the monitoring of heart transplant (HTx) rejection. In addition, EMB can have an important complementary role to the clinical assessment in establishing the diagnosis of diverse cardiac disorders, including myocarditis, cardiomyopathies, drug-related cardiotoxicity, amyloidosis, other infiltrative and storage disorders, and cardiac tumours. Improvements in EMB equipment and the development of new techniques for the analysis of EMB samples have significantly improved diagnostic precision of EMB. The present document is the result of the Trilateral Cooperation Project between the Heart Failure Association of the European Society of Cardiology, the Heart Failure Society of America, and the Japanese Heart Failure Society. It represents an expert consensus aiming to provide a comprehensive, up-to-date perspective on EMB, with a focus on the following main issues: (i) an overview of the practical approach to EMB, (ii) an update on indications for EMB, (iii) a revised plan for HTx rejection surveillance, (iv) the impact of multimodality imaging on EMB, and (v) the current clinical practice in the worldwide use of EMB.

Background In vitro studies suggest that phosphorylation of titin reduces myocyte/myofiber stiffness. Titin can be phosphorylated by cGMP activated protein kinase (PKG). Intracellular cGMP production is stimulated by B-type natriuretic peptide (BNP) and degraded by phosphodiesterases (PDE) including PDE-5A. We hypothesized that a PDE-5A inhibitor (sildenafil) alone or in combination with BNP would increase left ventricular (LV) diastolic distensibility by phosphorylating titin. Methods and Results 8 elderly dogs with experimental hypertension (OH) and 4 young normal (YN) dogs underwent measurement of the end-diastolic pressure (EDP) volume (EDV) relationship (EDPVR) during caval occlusion at baseline, after sildenafil and after BNP infusion. To assess diastolic distensibility independent of load/extrinsic forces, the EDV at a common EDP on the sequential EDPVRs was measured (LV capacitance). In a separate group of dogs (n=7 OH and 7 YN), serial full thickness LV biopsies were harvested from the beating heart during identical infusions to measure myofilament protein phosphorylation. Plasma cGMP increased with sildenafil and further with BNP (7.31±2.37 to 26.9±10.3 to 70.3±8.1 pmol/ml, P<0.001). LV diastolic capacitance increased with sildenafil and further with BNP (51.4±16.9 to 53.7±16.8 to 60.0±19.4 ml, P<0.001). Changes were similar in OH and YN dogs. There were no effects on phosphorylation of troponin I, troponin T, phospholamban, or myosin light chains −1 or −2. Titin phosphorylation increased with sildenafil and BNP, whereas titin-based cardiomyocyte stiffness decreased. Conclusion Acute cGMP enhancing treatment with sildenafil and BNP improves LV diastolic distensibility in vivo, in part, by phosphorylating titin.