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Background: Although heart failure with preserved ejection fraction (HFpEF) is a serious disease, only limited options are available for its treatment. Recent studies have analyzed the effects of phosphodiesterase (PDE) inhibitors, especially PDE5 and PDE3 inhibitors, in patients with HFpEF, with mixed outcomes. Methods: We searched PUBMED and EMBASE databases up to August 2021. Randomized controlled trials (RCTs) and clinical trials that tested the effects of PDE inhibitors on patients with HFpEF were included as eligible studies. Indicators of left ventricular (LV) function, pulmonary arterial pressure (PAP), right ventricular (RV) function, exercise capacity, and quality of life (QOL) were used to evaluate the efficacy of PDE inhibitors in HFpEF. Results: Six RCTs that reported in 7 studies were included to evaluate the efficiency of PDE inhibitors on HFpEF patients. In the pooled analysis, PDE inhibitors showed insignificant changes in the ratio of early diastolic mitral inflow to annular velocities, left atrial volume index, pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR), peak oxygen uptake, 6-minute walking test distance, as well as Kansas City Cardiomyopathy Questionnaire score. However, substantial improvement was observed in the tricuspid annular plane systolic excursion (TAPSE). Additionally, the regression analysis showed that PDE inhibitor administration time is a critical factor for the decrease in PASP. Conclusions: PDE inhibitors did not effectively improve LV function, PAP, exercise capacity, and QOL in patients with HFpEF. However, they improved RV function with significant difference, suggesting that PDE inhibitors might be a promising option for HFpEF patients with RV dysfunction.
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Background: Frailty is common in patients with heart failure (HF) and can adversely impact outcomes. Objectives: This study examined the prevalence of frailty among Asian patients with HF, its association with 1-year outcomes, and if race-ethnicity, HF subtypes, and sex modify this relationship. Methods: In the multinational ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) registry, a baseline frailty index (FI) was constructed using a cumulative deficits approach with 48 baseline variables, and patients were followed for the 1-year primary outcome of all-cause death or HF hospitalization. Results: Among 3,881 participants (age 61 ± 13 years, 27% female), the mean FI was 0.28 ± 0.11, and 69% were frail (FI >0.21). Higher FI was associated with older age, Malay ethnicity, and Southeast Asian residency. While comorbidities were more frequent in frail patients (by definition), body mass index was not different across frailty classes. Compared with FI class 1 (<0.21, nonfrail), FI class 2 (0.21-0.31) and FI class 3 (>0.31) had increased risk of the 1-year composite outcome (hazard ratios of 1.84 [95% confidence interval (CI): 1.42-2.38] and 4.51 [95% CI: 3.59-5.67], respectively), even after multivariable adjustment (adjusted hazard ratios of 1.49 [95% CI: 1.13-1.97] and 2.69 [95% CI: 2.06-3.50], respectively). Race-ethnicity modified the association of frailty with the composite outcome (P interaction = 0.0097), wherein the impact of frailty was strongest among Chinese patients. The association between frailty and outcomes did not differ between men and women (P interaction = 0.186) or for HF with reduced ejection fraction versus HF with preserved ejection fraction (P interaction = 0.094). Conclusions: Most Asian patients with HF are frail despite relatively young age. Our results reveal specific ethnic (Malay) and regional (Southeast Asia) predisposition to frailty and highlight its prognostic importance, especially in Chinese individuals. (ASIAN HF Registry, A Prospective Observational Study [ASIANHF]; NCT01633398).
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OBJECTIVE: To evaluate effects of atrial fibrillation (AF) on cardiac biomarkers and outcomes in a trial population of patients with heart failure (HF) with reduced ejection fraction treated with optimal guideline-directed medical therapy. METHODS: We performed a secondary analysis of 894 patients in the Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in Heart Failure (GUIDE-IT) trial (January 2013-July 2016). Patients were stratified by AF status and compared with regard to guideline-directed medical therapy use, longitudinal levels of N-terminal pro-B type natriuretic peptide (NT-proBNP), and outcomes including HF hospitalization and mortality. RESULTS: After adjustment, AF was associated with a significant increase in the risk of HF hospitalization or cardiovascular death (hazard ratio, 1.28; 95% CI, 1.02 to 1.61; P=0.04) and HF hospitalization (hazard ratio, 1.31; 95% CI, 1.02 to 1.68; P=.03) but with no difference in mortality during a median 15 months of follow-up. There were no significant differences in medication treatment between those with and those without AF. At 90 days, a higher proportion of patients with AF (89.4% vs 81.5%; P=.002) had an NT-proBNP level above 1000 pg/mL (to convert NT-proBNP values to pmol/L, multiply by 0.1182), and AF patients had higher NT-proBNP levels at all time points through 2 years of follow-up. CONCLUSION: Among patients with HF with reduced ejection fraction, prevalent AF was associated with higher NT-proBNP concentrations through 2 years of follow-up and higher risk for HF hospitalization despite no substantial differences in medical therapy.