Dapagliflozin and short-term changes on circulating antigen carbohydrate 125 in heart failure with reduced ejection fraction.

Circulating antigen carbohydrate 125 (CA125) has emerged as a proxy of fluid overload in heart failure. This study aimed to evaluate the effect of dapagliflozin on short-term CA125 levels in patients with stable heart failure with reduced ejection fraction (HFrEF) and whether these changes mediated the effects on peak oxygen consumption (peakVO2). This study is a post-hoc sub-analysis of a randomized, double-blinded clinical trial in which 90 stable patients with HFrEF were randomly assigned to receive either dapagliflozin or placebo to evaluate change in peakVO2 (NCT04197635). We used linear mixed regression analysis to compare changes in the natural logarithm of CA125 (logCA125) and percent changes from baseline (Δ%CA125). We used the "rwrmed" package to perform mediation analyses. CA125 was available in 87 patients (96.7%). LogCA125 significantly decreased in patients on treatment with dapagliflozin [1-month: Δ - 0.18, (CI 95% = - 0.33 to - 0.22) and 3-month: Δ - 0.23, (CI 95% = - 0.38 to - 0.07); omnibus p-value = 0.012]. Δ%CA125 decreased by 18.4% and 31.4% at 1 and 3-month, respectively (omnibus p-value = 0.026). Changes in logCA125 mediated the effect on peakVO2 by 20.4% at 1 month (p < 0.001). We did not find significant changes for natural logarithm of NTproBNP (logNT-proBNP) [1-month: Δ - 0.03, (CI 95% = - 0.23 to 0.17; p = 0.794), and 3-month: Δ 0.73, (CI 95% = - 0.13 to 0.28; p-value 0.489), omnibus p-value = 0.567]. In conclusion, in patients with stable HFrEF, dapagliflozin resulted in a significant reduction in CA125. Dapagliflozin was not associated with short-term changes in natriuretic peptides. These changes mediated the effects on peakVO2.

Frailty and prognosis of older patients with chronic heart failure.

INTRODUCTION AND OBJECTIVES: Heart failure (HF) is prevalent in advanced ages. Our objective was to assess the impact of frailty on 1-year mortality in older patients with ambulatory HF. METHODS: Our data come from the FRAGIC study (Spanish acronym for "Study of the impact of frailty and other geriatric syndromes on the clinical management and prognosis of elderly outpatients with heart failure"), a multicenter prospective registry conducted in 16 Spanish hospitals including outpatients ≥ 75 years with HF followed up by cardiology services in Spain. RESULTS: We included 499 patients with a mean age of 81.4±4.3 years, of whom 193 (38%) were women. A total of 268 (54%) had left ventricular ejection fraction <40%, and 84.6% was in NYHA II functional class. The FRAIL scale identified 244 (49%) pre-frail and 111 (22%) frail patients. Frail patients were significantly older, were more frequently female (both, P <.001), and had higher comorbidity according to the Charlson index (P=.017) and a higher prevalence of geriatric syndromes (P <.001). During a median follow-up of 371 [361-387] days, 58 patients (11.6%) died. On multivariate analysis (Cox regression model), frailty detected with the FRAIL scale was marginally associated with mortality (HR=2.35; 95%CI, 0.96-5.71; P=.059), while frailty identified by the visual mobility scale was an independent predictor of mortality (HR=2.26; 95%CI, 1.16-4.38; P=.015); this association was maintained after adjustment for confounding variables (HR=2.13; 95%CI, 1.08-4.20; P=.02). CONCLUSIONS: In elderly outpatients with HF, frailty is independently associated with mortality at 1 year of follow-up. It is essential to identify frailty as part of the comprehensive approach to elderly patients with HF.

Circulating circRNA as biomarkers for dilated cardiomyopathy etiology.

Dilated cardiomyopathy (DCM) is the third most common cause of heart failure. The multidisciplinary nature of testing - involving genetics, imaging, or cardiovascular techniques - makes its diagnosis challenging. Novel and reliable biomarkers are needed for early identification and tailored personalized management. Peripheral circular RNAs (circRNAs), a leading research topic, remain mostly unexplored in DCM. We aimed to assess whether peripheral circRNAs are expressed differentially among etiology-based DCM. The study was based on a case-control multicentric study. We enrolled 130 subjects: healthy controls (n = 20), idiopathic DCM (n = 30), ischemic DCM (n = 20), and familial DCM patients which included pathogen variants of (i) LMNA gene (n = 30) and (ii) BCL2-associated athanogene 3 (BAG3) gene (n = 30). Differentially expressed circRNAs were analyzed in plasma samples by quantitative RT-PCR and correlated to relevant systolic and diastolic parameters. The pathophysiological implications were explored through bioinformatics tools. Four circRNAs were overexpressed compared to controls: hsa_circ_0003258, hsa_circ_0051238, and hsa_circ_0051239 in LMNA-related DCM and hsa_circ_0089762 in the ischemic DCM cohort. The obtained areas under the curve confirm the discriminative capacity of circRNAs. The circRNAs correlated with some diastolic and systolic echocardiographic parameters with notable diagnostic potential in DCM. Circulating circRNAs may be helpful for the etiology-based diagnosis of DCM as a non-invasive biomarker. KEY MESSAGES: The limitations of cardiac diagnostic imaging and the absence of a robust biomarker reveal the need for a diagnostic tool for dilated cardiomyopathy (DCM). The circular RNA (circRNA) expression pattern is paramount for categorizing the DCM etiologies. Our peripheral circRNAs fingerprint discriminates between various among etiology-based DCM and correlates with some echocardiographic parameters. We provide a potential non-invasive biomarker for the etiology-based diagnosis of LMNA-related DCM and ischemic DCM.

Characteristics, treatments and 1-year prognosis of hospitalized and ambulatory heart failure patients with chronic obstructive pulmonary disease in the European Society of Cardiology Heart Failure Long-Term Registry.

AIMS: To describe the characteristics and assess the 1-year outcomes of hospitalized (HHF) and chronic (CHF) heart failure patients with chronic obstructive pulmonary disease (COPD) enrolled in a large European registry between May 2011 and April 2013. METHODS AND RESULTS: Overall, 1334/6920 (19.3%) HHF patients and 1322/9409 (14.1%) CHF patients were diagnosed with COPD. In both groups, patients with COPD were older, more frequently men, had a worse clinical presentation and a higher prevalence of co-morbidities. In HHF, the increase in the use of heart failure (HF) medications at hospital discharge was greater in non-COPD than in COPD for angiotensin-converting enzyme inhibitors (+13.7% vs. +7.2%), beta-blockers (+20.6% vs. +11.8%) and mineralocorticoid receptor antagonists (+20.9% vs. +17.3%), thus widening the gap in HF treatment already existing between the two groups at admission. In CHF patients, there was a similar increase in the use of these medications after enrollment visit in the two groups, leaving a significant difference of 8.2% for beta-blockers in favour of non-COPD patients (89.8% vs. 81.6%, P < 0.001). At 1-year follow-up, the hazard ratios for COPD in multivariable analysis confirmed its independent association with hospitalizations both in HHF [all-cause: 1.16 (1.04-1.29), for HF: 1.22 (1.05-1.42)] and CHF patients [all-cause: 1.26 (1.13-1.41), for HF: 1.37 (1.17-1.60)]. The association between COPD and all-cause mortality was not confirmed in both groups after adjustments. CONCLUSIONS: COPD frequently coexists in HHF and CHF, worsens the clinical course of the disease, and significantly impacts its therapeutic management and prognosis. The matter should deserve greater attention from the cardiology community.