Echo-derived pulmonary arterial systolic pressure (PASP) and right ventricular (RV) tricuspid annular plane systolic excursion (TAPSE; from the end of diastole to end-systole) are of basic relevance in the clinical follow-up of heart failure (HF) patients, carrying two- to threefold increase in cardiac risk when increased and reduced, respectively. We hypothesized that the relationship between TAPSE (longitudinal RV fiber shortening) and PASP (force generated by the RV) provides an index of in vivo RV length-force relationship, with their ratio better disclosing prognosis. Two hundred ninety-three HF patients with reduced (HFrEF, n = 247) or with preserved left ventricular (LV) ejection fraction (HFpEF, n = 46) underwent echo-Doppler studies and N-terminal pro-brain-type natriuretic peptide assessment and were tracked for adverse events. The median follow-up duration was 20.8 mo. TAPSE vs. PASP relationship showed a downward regression line shift in nonsurvivors who were more frequently presenting with higher PASP and lower TAPSE. HFrEF and HFpEF patients exhibited a similar distribution along the regression line. Given the TAPSE, PASP, and TAPSE-to-PASP ratio (TAPSE/PASP) collinearity, separate Cox regression and Kaplan-Meier analyses were performed: one with TAPSE and PASP as individual measures, and the other combining them in ratio form. Hazard ratios for variables retained in the multivariate regression were as follows: TAPSE/PASP </≥ 0.36 mm/mmHg [hazard ratio (HR): 10.4, P < 0.001]; TAPSE </≥ 16 mm (HR: 5.1, P < 0.01); New York Heart Association functional class </≥ 3 (HR: 4.4, P < 0.001); E/e’ (HR: 4.1, P < 0.001). This study shows that the TAPSE vs. PASP relationship is shifted downward in nonsurvivors with a similar distribution in HFrEF and HFpEF, and their ratio improves prognostic resolution. The TAPSE vs. PASP relationship as a possible index of the length-force relationship may be a step forward for a more efficient RV function evaluation and is not affected by the quality of LV dysfunction.

Background— Several mortality risk scores exist in cardiac surgery. All include a considerable number of independent risk factors. In elective cardiac surgery patients, the operative mortality is low, the number of events recorded per year is limited, and the risk model may be overfitted. The present study aims to develop and validate an operative mortality risk score for elective patients based on a limited number of factors. Methods and Results— The development series included 4557 adult patients who had undergone an elective cardiac operation at our institution from 2001 to 2003; the validation series includes the 4091 patients who subsequently underwent an operation. Three independent factors were included in the mortality risk model: age, creatinine, and left ventricular ejection fraction (ACEF). The ACEF score was computed as follows: age (years)/ejection fraction (%)+1 (if serum creatinine value was >2 mg/dL). The ACEF score was compared with 5 other risk scores in the validation series. Discriminatory power (accuracy) was defined with a receiver-operating characteristics analysis. The best accuracy was achieved by the Cleveland Clinic score (0.812), with ACEF score just below it (0.808). In coronary operations, the 2 scores performed equally well (0.815 versus 0.813), and in isolated coronary operations, the best accuracy was achieved by ACEF (0.826), with the Cleveland Clinic score at 0.806. Conclusion— A risk model limited to 3 independent predictors has similar or better accuracy and calibration compared with more complex risk scores if applied to elective cardiac operations.

Increased morbidity and mortality associated with ischemic heart failure (HF) in type 2 diabetic patients requires a deeper understanding of the underpinning pathogenetic mechanisms. Given the implication of microRNAs (miRNAs) in HF, we investigated their regulation and potential role. miRNA expression profiles were measured in left ventricle biopsies from 10 diabetic HF (D-HF) and 19 nondiabetic HF (ND-HF) patients affected by non–end stage dilated ischemic cardiomyopathy. The HF groups were compared with each other and with 16 matched nondiabetic, non-HF control subjects. A total of 17 miRNAs were modulated in D-HF and/or ND-HF patients when compared with control subjects. miR-216a, strongly increased in both D-HF and ND-HF patients, negatively correlated with left ventricular ejection fraction. Six miRNAs were differently expressed when comparing D-HF and ND-HF patients: miR-34b, miR-34c, miR-199b, miR-210, miR-650, and miR-223. Bioinformatic analysis of their modulated targets showed the enrichment of cardiac dysfunctions and HF categories. Moreover, the hypoxia-inducible factor pathway was activated in the noninfarcted, vital myocardium of D-HF compared with ND-HF patients, indicating a dysregulation of the hypoxia response mechanisms. Accordingly, miR-199a, miR-199b, and miR-210 were modulated by hypoxia and high glucose in cardiomyocytes and endothelial cells cultured in vitro. In conclusion, these findings show a dysregulation of miRNAs in HF, shedding light on the specific disease mechanisms differentiating diabetic patients.

Long noncoding RNAs (lncRNAs) are non-protein coding transcripts regulating a variety of physiological and pathological functions. However, their implication in heart failure is still largely unknown. The aim of this study is to identify and characterize lncRNAs deregulated in patients affected by ischemic heart failure. LncRNAs were profiled and validated in left ventricle biopsies of 18 patients affected by non end-stage dilated ischemic cardiomyopathy and 17 matched controls. Further validations were performed in left ventricle samples derived from explanted hearts of end-stage heart failure patients and in a mouse model of cardiac hypertrophy, obtained by transverse aortic constriction. Peripheral blood mononuclear cells of heart failure patients were also analyzed. LncRNA distribution in the heart was assessed by in situ hybridization. Function of the deregulated lncRNA was explored analyzing the expression of the neighbor mRNAs and by gene ontology analysis of the correlating coding transcripts. Fourteen lncRNAs were significantly modulated in non end-stage heart failure patients, identifying a heart failure lncRNA signature. Nine of these lncRNAs (CDKN2B-AS1/ANRIL, EGOT, H19, HOTAIR, LOC285194/TUSC7, RMRP, RNY5, SOX2-OT and SRA1) were also confirmed in end-stage failing hearts. Intriguingly, among the conserved lncRNAs, h19, rmrp and hotair were also induced in a mouse model of heart hypertrophy. CDKN2B-AS1/ANRIL, HOTAIR and LOC285194/TUSC7 showed similar modulation in peripheral blood mononuclear cells and heart tissue, suggesting a potential role as disease biomarkers. Interestingly, RMRP displayed a ubiquitous nuclear distribution, while H19 RNA was more abundant in blood vessels and was both cytoplasmic and nuclear. Gene ontology analysis of the mRNAs displaying a significant correlation in expression with heart failure lncRNAs identified numerous pathways and functions involved in heart failure progression. These data strongly suggest lncRNA implication in the molecular mechanisms underpinning HF.