Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disorder developing from multiple aetiologies with overlapping pathophysiological mechanisms. HFpEF diagnosis may be challenging, as neither cardiac imaging nor physical examination are sensitive in this situation. Here, we review biomarkers of HFpEF, of which the best supported are related to myocardial stretch and injury, including natriuretic peptides and cardiac troponins. An overview of biomarkers of inflammation, extracellular matrix derangements and fibrosis, senescence, vascular dysfunction, anaemia/iron deficiency and obesity is also provided. Finally, novel biomarkers from -omics technologies, including plasma metabolites and circulating microRNAs, are outlined briefly. A cardiac-centred approach to HFpEF diagnosis using natriuretic peptides seems reasonable at present in clinical practice. A holistic approach including biomarkers that provide information on the non-cardiac components of the HFpEF syndrome may enrich our understanding of the disease and may be useful in classifying HFpEF phenotypes or endotypes that may guide patient selection in HFpEF trials.

Aims: To investigate the distribution of left atrioventricular coupling index (LACI) among patients with heart failure and left ventricular ejection fraction (LVEF) < 50% and to explore its association with the combined endpoint of all-cause death or HF hospitalization at long-term follow-up. Methods and results: Patients with HF and LVEF < 50% undergoing cardiac magnetic resonance were evaluated. Patients with atrial fibrillation or flutter were excluded. Left atrioventricular coupling index was measured as the ratio between the left atrial (LA) and the LV end-diastolic volumes. Patient population was divided according to LACI tertiles and followed up. Total of 478 patients (mean age 62 ± 12 years, 78% male) were included. The median value of LACI was 27.1% (interquartile range 19.9–34.5). Patients within the worst LACI tertile (≥30.9%) showed smaller LV volumes and larger LA volumes as compared with patients in the first or second tertile (LACI 6.2–22.2 and LACI 22.3–30.9, respectively). Left atrioventricular coupling index was significantly associated with the combined endpoint [hazard ratio (HR) 1.87, P = 0.01]. After adjusting for sex, age, ischaemic HF aetiology, LVEF, LA reservoir strain, diabetes mellitus, LV scar, mitral regurgitation, and LVEDVi, LACI remained significantly associated with the combined endpoint (HR 1.77, P = 0.02). Patients with the highest LACI values had worse outcomes compared with patients in first and second tertiles (HR 1.69, P = 0.02 and HR 1.77, P = 0.02, respectively). Conclusion: In patients with HF and LVEF <50%, LACI is independently associated with adverse events. Patients with most impaired left atrioventricular coupling have the worst clinical outcomes.

Severe tricuspid regurgitation remains a challenging heart-valve disease to effectively treat with high morbidity and mortality at mid-term. Currently guideline-directed medical treatment is limited to escalating dose of diuretics, and the rationale and timing of open-heart surgery remains controversial. Emerging percutaneous therapies for severe tricuspid regurgitation continue to show promising results in early feasibility studies. However, randomized trial data is lacking. Additionally, many patients are deemed unsuitable for these emerging therapies due to anatomical or imaging constraints. Given the technical simplicity of the bicaval valve implantation (CAVI) technique compared to other transcatheter devices, CAVI is postulated as a suitable alternative for a wide variety of patients affected with severe+ tricuspid regurgitation. In this review we illustrate the current evidence and ongoing uncertainties of CAVI, focusing on the novel CAVI-specific devices.

Aim: Patients with advanced heart failure (AHF) who are not candidates to advanced therapies have poor prognosis. Some trials have shown that intermittent levosimendan can reduce HF hospitalizations in AHF in the short term. In this real-life registry, we describe the patterns of use, safety and factors related to the response to intermittent levosimendan infusions in AHF patients not candidates to advanced therapies. Methods and results: Multicentre retrospective study of patients diagnosed with advanced heart failure, not HT or LVAD candidates. Patients needed to be on the optimal medical therapy according to their treating physician. Patients with de novo heart failure or who underwent any procedure that could improve prognosis were not included in the registry. Four hundred three patients were included; 77.9% needed at least one admission the year before levosimendan was first administered because of heart failure. Death rate at 1 year was 26.8% and median survival was 24.7 [95% CI: 20.4–26.9] months, and 43.7% of patients fulfilled the criteria for being considered a responder lo levosimendan (no death, heart failure admission or unplanned HF visit at 1 year after first levosimendan administration). Compared with the year before there was a significant reduction in HF admissions (38.7% vs. 77.9%; P < 0.0001), unplanned HF visits (22.7% vs. 43.7%; P < 0.0001) or the combined event including deaths (56.3% vs. 81.4%; P < 0.0001) during the year after. We created a score that helps predicting the responder status at 1 year after levosimendan, resulting in a score summatory of five variables: TEER (+2), treatment with beta-blockers (+1.5), Haemoglobin >12 g/dL (+1.5), amiodarone use (−1.5) HF visit 1 year before levosimendan (−1.5) and heart rate >70 b.p.m. (−2). Patients with a score less than −1 had a very low probability of response (21.5% free of death or HF event at 1 year) meanwhile those with a score over 1.5 had the better chance of response (68.4% free of death or HF event at 1 year). LEVO-D score performed well in the ROC analysis. Conclusion: In this large real-life series of AHF patients treated with levosimendan as destination therapy, we show a significant decrease of heart failure events during the year after the first administration. The simple LEVO-D Score could be of help when deciding about futile therapy in this population.