|dc.description.abstracteng||In recent decades, heart failure (HF) with preserved left ventricular ejection fraction (HFpEF) has become an important issue in both cardiovascular research and clinical practice. Several studies show that more than half of patients with signs or symptoms of HF have preserved left ventricular systolic function. In addition, the relative proportion of HFpEF compared to HF with reduced ejection fraction (HFrEF) increased significantly. The diagnosis of HFpEF is challenging and requires based on the recommendations of the European Society of Cardiology (ESC) a triad of (1) signs or symptoms of HF, (2) a left ventricular ejection fraction (LVEF) > 50%, and (3) evidence of diastolic dysfunction (DD) (Paulus et al. 2007). However, clinical associations and influencing factors, as well as the prognostic significance of the diagnosis made as recommended above have not been investigated. The aim of this study was therefore to prospectively evaluate the ESC diagnostic algorithm for HFpEF in a population-based cohort.
1727 patients (aged 50-85 years) with ≥ 1 cardiovascular risk factor or a history of HF were enrolled in the multi-center, prospective cohort study (Diast-CHF-study). For further analysis, patients with LVEF < 50% or missing key parameters of ventricular function were excluded. The remaining 1498 patients (age 66.7 ± 8.1 years, 51.1% female, BMI 29.1 ± 4.8 kg/m2, LVEF 61.4 ± 6.4%) were followed up for 5.2 (4.8 - 5.6) years. At baseline, the presence or absence of DD according to the non-invasive diagnostic criteria of the ESC algorithm (termed as “Paulus positive” and “Paulus negative”, respectively) and signs/symptoms of HF (defined as ≥ 2 HF signs or symptoms) were assessed. Beside a sophisticated echocardiographic evaluation, baseline examination included i. a. a six-minute-walk-test (6MWT), determination of NT-proBNP and SF-36 physical functioning scale (SF-36). Five-year follow-up was performed in a standardized manner (n = 1430).
412 (27.5%) of the 1498 patients were "Paulus positive", 647 (43.2%) showed HF signs/symptoms. According to Paulus et al. (2007), 231 patients (15.4%) met the required criteria for the diagnosis of HFpEF. Using a logistic regression model, independent predictors for "Paulus positive" were identified. In this analysis, signs/symptoms of HF, age, female gender, HF history, coronary artery disease (CAD), pulse pressure and anaemia were significantly predictive for having diastolic dysfunction according to Paulus et al. (2007). In addition, the impact of "Paulus positive" on physical capacity was investigated. “Paulus positive" was related to significant limitations in 6MWT and SF-36 in an unadjusted model. After full adjustment, the association between “Paulus positive” and SF-36 persisted. For further analysis, patients were categorized into 1 of 4 groups (Group (G) 1: "Paulus positive" and ≥ 2 HF signs/symptoms, G2: "Paulus positive" and no HF signs/symptoms, G3: "Paulus negative" and ≥ 2 HF signs/symptoms, G4: "Paulus negative" and no HF signs/symptoms). The occurrence of the primary outcome (death or cardiovascular hospitalization) was significantly different across the four groups (p < 0,001), with group 1 being associated with the highest risk. After full adjustment, “Paulus positive”, age, CAD and pulse pressure were significantly related to the primary outcome.
Summing up, this is the first comprehensive study investigating clinical associations and prognostic significance of the ESC consensus algorithm for diagnosis of HFpEF. The combination of diastolic dysfunction and HF signs/symptoms in patients with preserved LVEF, as postulated in this algorithm, was associated with the highest risk of death or cardiovascular hospitalization over 5.2 years. The identified independent predictors for "Paulus positive" may play an important role e.g. in early diagnosis and prevention of DD and HFpEF. However, further studies are needed to confirm our results and to identify mechanisms explaining the ominous prognosis.||de