Heart failure with preserved ejection fraction: A clustering approach to a heterogenous syndrome.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome at the crossroads of multiple co-morbidities; there is no valid treatment for this condition. Defining new phenotypes could play a role in improving treatment and prognosis. AIM: To identify groups with different pathophysiologies by applying a clustering approach to a multicentric cohort of patients with HFpEF. METHODS: A total of 538 patients from the multicentre KaRen study were included. Accurate clinical, biological and ultrasound data are available, with a mean follow-up of 28 months. Based on a clustering analysis, the population was separated into groups based on 55 variables, comparing distribution of deaths and hospitalizations between groups. RESULTS: Three clusters were identified from 356 analysable patients (mean age 76.1±9.31 years; 43.5% men): cluster 1 (n=128) comprised overweight, relatively young men at high cardiovascular risk, in sinus rhythm, with altered renal function; cluster 2 (n=134) comprised women, most of whom had conserved left ventricular function; cluster 3 (n=94) had the highest incidence of mitral regurgitation, atrial remodelling and rhythm disorders. There were no significant differences, only a trend towards early mortality in cluster 3. CONCLUSIONS: Clustering analysis seems to be effective at individualizing subgroups with different physiopathologies in HFpEF. The clinical relevance of these phenotypes needs to be studied, and may concern treatment strategy more than prognostic differences.

Importance of combined left atrial size and estimated pulmonary pressure for clinical outcome in patients presenting with heart failure with preserved ejection fraction.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome with various phenotypes and outcomes. The prognostic relevance of echocardiography and the E/e' ratio has previously been reported. We sought to study in addition, the value of estimated pulmonary pressure and left atrial size for diagnosing and determining a prognosis for HFpEF-patients in a prospective multi-centric cohort. METHODS AND RESULTS: Patients with an acute-HF event accompanied with NT-proBNP >300 pg/mL (BNP >100 pg/mL) and LVEF >45% were included (n = 237) and clinically reassessed using echo-Doppler after 4-8 weeks of HF treatment as part of the prospective KaRen HFpEF study. A core-centre performed the echocardiographic analyses. A combined primary endpoint of either HF hospitalizations and mortality over a span of 18-month, or simply mortality (secondary endpoint) were used. The mean LVEF was 62 ± 7%, E/e':12.9 ± 6.0, left atrial volume index (LAVI): 48.1 ± 15.9 ml/m2, TR: 2.9 ± 0.9 m/s. Patients with both LAVI > 40 ml/m2 and TR > 3.1 m/s had a significantly greater risk of death or heart failure related hospitalization than others (P = 0.014 after adjustment). CONCLUSION: The combination of enlarged LA and elevated estimated pulmonary pressure has a strong prognostic impact in patients suffering from HFpEF. Our results indicate that such patients constitute a risk group in HFpEF which requires dedicated medical attention. CLINICALTRIALS.GOV: NCT00774709.