Long-term clinical experience with cardiac contractility modulation therapy delivered by the Optimizer Smart system.

AIMS: We assessed long-term effects of cardiac contractility modulation delivered by the Optimizer Smart system on quality of life, left ventricular ejection fraction (LVEF), mortality and heart failure and cardiovascular hospitalizations. METHODS AND RESULTS: CCM-REG is a prospective registry study including 503 patients from 51 European centres. Effects were evaluated in three terciles of LVEF (≤25%, 26-34% and ≥35%) and in patients with atrial fibrillation (AF) and normal sinus rhythm (NSR). Hospitalization rates were compared using a chi-square test. Changes in functional parameters of New York Heart Association (NYHA) class, Minnesota Living with Heart Failure Questionnaire (MLWHFQ) and LVEF were assessed with Wilcoxon signed-rank test, and event-free survival by Kaplan-Meier analysis. For the entire cohort and each subgroup, NYHA class and MLWHFQ improved at 6, 12, 18 and 24 months (P < 0.0001). At 24 months, NYHA class, MLWHFQ and LVEF showed an average improvement of 0.6 ± 0.7, 10 ± 21 and 5.6 ± 8.4%, respectively (all P < 0.001). LVEF improved in the entire cohort and in the LVEF ≤25% subgroup with AF and NSR. In the overall cohort, heart failure hospitalizations decreased from 0.74 [95% confidence interval (CI) 0.66-0.82] prior to enrolment to 0.25 (95% CI 0.21-0.28) events per patient-year during 2-year follow-up (P < 0.0001). Cardiovascular hospitalizations decreased from 1.04 (95% CI 0.95-1.13) events per patient-year prior to enrolment to 0.39 (95% CI 0.35-0.44) events per patient-year during 2-year follow-up (P < 0.0001). Similar reductions of hospitalization rates were observed in the LVEF, AF and NSR subgroups. Estimated survival was significantly better than predicted by MAGGIC at 1 and 3 years in the entire cohort and in the LVEF 26-34% and ≥35% subgroups. CONCLUSIONS: Cardiac contractility modulation therapy improved functional status, quality of life, LVEF and, compared to patients' prior history, reduced heart failure hospitalization rates. Survival at 1 and 3 years was significantly better than predicted by the MAGGIC risk score.

Clinical effects of cardiac contractility modulation in heart failure with mildly reduced systolic function.

AIMS: Increasing attention is being given to patients with heart failure and 'mid-range' left ventricular ejection fraction (LVEF, ≥40% and <50%) for whom there are no approved therapies that improve prognosis. We aim to assess for the first time the effects of cardiac contractility modulation (CCM) therapy in this patient population. METHODS AND RESULTS: We assessed the effects of 6-  month CCM therapy on functional status, exercise tolerance and quality of life in a subgroup of 53 patients with a LVEF of 40-45% recruited in previous CCM studies, including 37 patients in the CCM group and 16 in the control group. New York Heart Association classification improved by ≥1 class from baseline to 24 weeks in 80.6% (95% confidence interval [62.5%, 92.5%]) of patients in the CCM group compared with 57.1% in the control group (95% confidence interval [28.9%, 82.3%], P = 0.15). Six-minute walk distance increased significantly in the CCM group with a net between-group treatment effect of 53.9 ± 74.2 m (P = 0.05). Peak VO2 improved in the CCM group with a net between-group treatment effect of 2.0 ± 2.8 mL/kg/min (P = 0.02). Minnesota Living with Heart Failure Questionnaire score decreased from baseline to 24 weeks with a net between-group treatment effect of -13.1 ± 21.0 (P = 0.10). There were no significant differences in the adverse event rate between the CCM and control groups. CONCLUSIONS: These preliminary results suggest that CCM exerts favourable effects on exercise tolerance and quality of life in patients with LVEF in the range of 40-45% with an acceptable safety profile. Further randomized controlled studies are planned to prove these effects.

Hemodynamic effects of partial ventricular support in chronic heart failure: results of simulation validated with in vivo data.

OBJECTIVE: Current left ventricular assist devices are designed to provide full hemodynamic support for patients with end-stage failing hearts, but their use has been limited by operative risks, low reliability, and device-related morbidity. Such concerns have resulted in minimum use of left ventricular assist devices for destination therapy. We hypothesize that partial circulatory support, which could be achieved with small pumps implanted with less-invasive procedures, might expand the role of circulatory support devices for treatment of heart failure. METHODS: We examine the hemodynamic effects of partial left ventricular support using a previously described computational model of the cardiovascular system. Results from simulations were validated by comparison with an in vivo hemodynamic study. RESULTS: Simulations demonstrated that partial support (2-3 L/min) increased total cardiac output (left ventricular assist device output plus native heart output) by more than 1 L/min and decreased left ventricular end-diastolic pressure by 7 to 10 mm Hg with moderate-to-severe heart failure. Analyses showed that the hemodynamic benefits of increased cardiac output and decreased left ventricular end-diastolic pressure are greater in less-dilated and less-dysfunctional hearts. Both the relationships between ventricular assist device flow and cardiac output and ventricular assist device flow and left atrial pressure predicted by the model closely approximated the same relationships obtained during hemodynamic study in a bovine heart failure model. CONCLUSIONS: Results suggest that a pump with a flow rate of 2 to 3 L/min could meaningfully affect cardiac output and blood pressure in patients with advanced compensated heart failure. The development of small devices capable of high reliability and minimal complications that can be implanted with less-invasive techniques is supported by these findings.