Oxidative stress and mitochondrial dysfunction are hallmarks of heart failure (HF). Coenzyme Q10 (CoQ10) is a vitamin-like organic compound widely expressed in humans as ubiquinol (reduced form) and ubiquinone (oxidized form). CoQ10 plays a key role in electron transport in oxidative phosphorylation of mitochondria. CoQ10 acts as a potent antioxidant, membrane stabilizer and cofactor in the production of adenosine triphosphate by oxidative phosphorylation, inhibiting the oxidation of proteins and DNA. Patients with HF showed CoQ10 deficiency; therefore, a number of clinical trials investigating the effects of CoQ10 supplementation in HF have been conducted. CoQ10 supplementation may confer potential prognostic advantages in HF patients with no adverse hemodynamic profile or safety issues. The latest evidence on the clinical effects of CoQ10 supplementation in HF was reviewed.

Aims Cardiac contractility modulation, also referred to as CCM ™ , has emerged as a promising device treatment for heart failure (HF) in patients not indicated for cardiac resynchronization therapy. We performed a comprehensive individual patient data meta-analysis of all non-confounded prospective randomized controlled trials of CCM vs. control that have measured functional capacity and/or quality of life questionnaires in patients with HF. Methods and results The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE were searched in January 2020 to identify eligible randomized controlled trials. We also asked the sole manufacturer of the device for their list of known trials. Primary outcomes of interest were peak oxygen consumption (peak VO 2), 6 min walk test distance, and quality of life measured by Minnesota Living with Heart Failure Questionnaire (MLWHFQ), and all data were received as individual patient and individual time point data-points. Mean differences and 95% confidence intervals (CIs) were calculated for continuous data using a fixed-effects model. Five trials were identified, four randomized studies enrolling 801 participants for all endpoints of interest, and for peak VO 2 alone (n = 60), there was an additional single arm non-randomized trial (FIX-HF-5C2) with a prospective comparison of its 24 week peak VO 2 data compared with the control group of the FIX-HF-5C control patients. Pooled analysis showed that, compared with control, CCM significantly improved peak VO 2 (mean difference +0.93, 95% CI 0.56 to 1.30 mL/kg/min, P < 0.00001), 6 min walk test distance (mean difference +17.97, 95% CI 5.48 to 30.46 m, P = 0.005), and quality of life measured by MLWHFQ (mean difference À7.85, 95% CI À10.76 to À4.94, P < 0.00001). As a sensitivity analysis, we excluded the FIX-HF-5C2 trial (only relevant for peak VO 2), and the result was similar, mean difference +0.65, 95% CI 0.21 to 1.08 mL/kg/min, P = 0.004. Conclusions This comprehensive meta-analysis of individual patient data from all known randomized trials has shown that CCM provides statistically significant and clinically meaningful benefits in measures of functional capacity and HF-related quality of life.

Cancer and cardiovascular diseases are globally the leading causes of mortality and morbidity. These conditions are closely related, beyond that of sharing many risk factors. The term bidirectional relationship indicates that cardiovascular diseases increase the likelihood of getting cancer and vice versa. The biological and biochemical pathways underlying this close relationship will be analyzed. In this new overlapping scenario, physical activity and exercise are proven protective behaviors against both cardiovascular diseases and cancer. Many observational studies link an increase in physical activity to a reduction in either the development or progression of cancer, as well as to a reduction in risk in cardiovascular diseases, a non-negligible cause of death for long-term cancer survivors. Exercise is an effective tool for improving cardio-respiratory fitness, quality of life, psychological wellbeing, reducing fatigue, anxiety and depression. Finally, it can counteract the toxic effects of cancer therapy. The protection obtained from physical activity and exercise will be discussed in the various stages of the cancer continuum, from diagnosis, to adjuvant therapy, and from the metastatic phase to long-term effects. Particular attention will be paid to the shelter against chemotherapy, radiotherapy, cardiovascular risk factors or new onset cardiovascular diseases. Cardio-Oncology Rehabilitation is an exercise-based multi-component intervention, starting from the model of Cardiac Rehabilitation, with few modifications, to improve care and the prognosis of a patient’s cancer. The network of professionals dedicated to Cardiac Rehabilitation is a ready-to-use resource, for implementing Cardio-Oncology Rehabilitation.

Aims Functional mitral regurgitation (MR) (FMR) is common in heart failure with reduced ejection fraction and worsens morbidity and mortality, even when mild. The CARILLON® mitral contour system (Cardiac Dimensions, Kirkland, WA, USA), a mitral annuloplasty device delivered percutaneously to the coronary sinus, is designed to reduce the mitral annular dimension by virtue of the close anatomic relationship between the coronary sinus and the posterior mitral annulus. We performed a comprehensive individual patient data meta‐analysis of all studies that used CARILLON® device vs. control that have measured mitral regurgitation severity, left ventricular (LV) remodelling, functional status, and heart failure‐related outcomes in heart failure with reduced ejection fraction patients. Methods and results The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE were searched in July 2020. Primary outcomes of interest were measures of MR severity, LV remodelling, New York Heart Association functional class and heart failure‐related outcomes [mortality and heart failure hospitalization (HFH) during follow up]. All data were received as individual patient and individual time point data‐points. Mean differences and 95% confidence intervals (CIs) were calculated for continuous data using a fixed‐effects model. Three studies (REDUCE FMR, TITAN and TITAN II) enrolling 209 participants were identified and included. Pooled analysis showed that, compared with control, CARILLON® device significantly improved both MR volume (mean difference MD ‐9.20, 95% C.I. −16.11 to −2.29 mL, P = 0.009) and MR grade (MD ‐1.12, 95% CI −1.36 to −0.88, P < 0.00001) and this was associated with a significant reduction in LA volume, MD −7.54 mL, 95% CI −14.90 to − 0.18, P = 0.04. Significant LV reverse remodelling was also seen in terms of EDV (MD −16.53, 95% CI −28.61 to −44.4 mL, P = 0.007), and a trend in ESV (MD −8.68, 95% CI −18.69 to −1.34 mL, P = 0.09) but no significant effect on LVEF (MD 0.88, 95% CI −1.52% to 2.38%, P = 0.47), due presumably to the greater residual MR in the control patients falsely elevating the LVEF. In addition, the CARILLON® device significantly improved New York Heart Association functional Class (MD −0.22, 95% CI −0.24 to −0.16, P < 0.00001), associated with a lower rate of HFH compared with controls (45.3% vs. 64%, respectively, P = 0.04). As a sensitivity analysis we also restricted the analyses to those patients with Class 3+/4+ MR at baseline. In this cohort, the echocardiographic results were similar, and the reduction in HFH rates was even more marked (43.9% vs. 82.9%, respectively, P = 0.04). Conclusions This comprehensive meta‐analysis of individual patient data has shown that CARILLON® device provides statistically significant and clinically meaningful benefits on MR severity, LA and LV volumes, and remodelling and rates of subsequent heart failure hospitalization

Background: Heart rate recovery (HRR) is a marker of vagal tone, which is a powerful predictor of mortality in patients with cardiovascular disease. Sacubitril/valsartan (S/V) is a treatment for heart failure with reduced ejection fraction (HFrEF), which impressively impacts cardiovascular outcome. This study aims at evaluating the effects of S/V on HRR and its correlation with cardiopulmonary indexes in HFrEF patients. Methods: Patients with HFrEF admitted to outpatients’ services were screened out for study inclusion. S/V was administered according to guidelines. Up-titration was performed every 4 weeks when tolerated. All patients underwent laboratory measurements, Doppler-echocardiography, and cardiopulmonary exercise stress testing (CPET) at baseline and at 12-month follow-up. Results: Study population consisted of 134 HFrEF patients (87% male, mean age 57.9 ± 9.6 years). At 12-month follow-up, significant improvement in left ventricular ejection fraction (from 28% ± 5.8% to 31.8% ± 7.3%, p < 0.0001), peak exercise oxygen consumption (VO2peak) (from 15.3 ± 3.7 to 17.8 ± 4.2 mL/kg/min, p < 0.0001), the slope of increase in ventilation over carbon dioxide output (VE/VCO2 slope )(from 33.4 ± 6.2 to 30.3 ± 6.5, p < 0.0001), and HRR (from 11.4 ± 9.5 to 17.4 ± 15.1 bpm, p = 0.004) was observed. Changes in HRR were significantly correlated to changes in VE/VCO2slope (r = −0.330; p = 0.003). After adjusting for potential confounding factors, multivariate analysis showed that changes in HRR were significantly associated to changes in VE/VCO2slope (Beta (B) = −0.975, standard error (SE) = 0.364, standardized Beta coefficient (Bstd) = −0.304, p = 0.009). S/V showed significant reduction in exercise oscillatory ventilation (EOV) detection at CPET (28 EOV detected at baseline CPET vs. 9 EOV detected at 12-month follow-up, p < 0.001). HRR at baseline CPET was a significant predictor of EOV at 12-month follow-up (B = −2.065, SE = 0.354, p < 0.001). Conclusions: In HFrEF patients, S/V therapy improves autonomic function, functional capacity, and ventilation. Whether these findings might translate into beneficial effects on prognosis and outcome remains to be elucidated.