The C-CURE trial implements the paradigm of lineage guidance in cell therapy. Cardiopoietic stem cell therapy was found feasible and safe with signs of benefit in chronic heart failure, meriting definitive clinical evaluation. (C-Cure Clinical Trial; NCT00810238).

Background: Surgical aortic valve replacement (SAVR) represents a class I indication in symptomatic patients with severe aortic stenosis (AS). However, indications for early SAVR in asymptomatic patients with severe AS and normal left ventricular function remain debated. Methods: The Aortic Valve replAcemenT versus conservative treatment in Asymptomatic seveRe aortic stenosis (AVATAR) trial is an investigator-initiated international prospective randomized controlled trial that evaluated the safety and efficacy of early SAVR in the treatment of asymptomatic patients with severe AS, according to common criteria (valve area ≤1 cm 2 with aortic jet velocity >4 m/s or a mean trans-aortic gradient ≥40 mm Hg), and with normal LV function. Negative exercise testing was mandatory for inclusion. The primary hypothesis was that early SAVR would reduce the primary composite endpoint of all-cause death, acute myocardial infarction, stroke or unplanned hospitalization for heart failure, as compared to a conservative strategy according to guidelines. The trial was designed as event-driven to reach a minimum of 35 prespecified events. The study was performed in 9 centers in 7 European countries. Results: Between June 2015 and September 2020, 157 patients (mean age 67 years, 57 % men) were randomly allocated to early surgery (n=78) or conservative treatment (n=79). Follow-up was completed in May 2021. Overall median follow-up was 32 months: 28 months in the early surgery group and 35 months in the conservative treatment group. There was a total of 39 events, 13 in early surgery and 26 in conservative treatment group. In the early surgery group, 72 patients (92.3 %) underwent SAVR with operative mortality of 1.4 %. In an intention-to-treat analysis, patients randomized to early surgery had a significantly lower incidence of primary composite endpoint than those in the conservative arm (HR 0.46, 95 % CI 0.23-0.90, p=0.02). There was no statistical difference in secondary endpoints, including all-cause mortality, first heart failure hospitalizations, major bleeding or thromboembolic complications, but trends were consistent with the primary outcome. Conclusions: In asymptomatic patients with severe AS, early surgery reduced a primary composite of all-cause death, acute myocardial infarction, stroke or unplanned hospitalization for heart failure compared with conservative treatment. This randomized trial provides preliminary support for early SAVR once AS becomes severe, regardless of symptoms.

Background: Heart failure with preserved ejection fraction (HFpEF) is commonly associated with hypertension (HTN). However, resting echocardiography (ECHO) can underestimate the severity of disease. Exercise stress echocardiography (ESE) and the cardiopulmonary exercise testing (CPX) appeared to be useful tests in dynamic assessment of HFpEF. The value of combined exercise stress echocardiography cardiopulmonary testing (ESE-CPX) in the identification of masked HFpEF is still undetermined. Objective: The purpose of this study was to analyse the value of the combined ESE-CPX in the identification of masked HFpEF in patients with HTN, dyspnoea and normal resting left ventricular (LV) systolic and diastolic function. Methodology: We studied 87 patients with HTN, exertional dyspnoea and normal resting LV function. They all underwent ESE-CPX testing (supine bicycle, ramp protocol, 15 W/min). ECHO measurements were performed at rest, and at peak load. Achievement of peak E/e' ratio>15 was a marker for masked HFpEF. Results: Increase of E/e'>15 occurred in 8/87 patients (9.2%) during ESE-CPX. Those patients had the lower peak VO2 (p ¼ 0.012), the lower VO2 at anaerobic threshold (p ¼ 0.025), the lower workload (p ¼ 0.026), the lower peak partial pressure end tidal carbon dioxide (PetCO2) (p < 0.0001), and the higher VE/VCO2 slope (p < 0.0001) which was an independent multivariate predictor of HFpEF (p ¼ 0.021), with the cut-off value of 32.95 according to the receiveroperator characteristic (ROC) curve (sensitivity (Sn) 100%, specificity (Sp) 90%). Conclusion: The combined ESE-CPX test is feasible and reliable test that can unmask HFpEF and may become an important aid in the early diagnosis of HFpEF, excluding the other causes of exertional dyspnoea.