Effects of Cardiac Contractility Modulation Electrodes on Tricuspid Regurgitation in Patients with Heart Failure with Reduced Ejection Fraction: A Pilot Study.

BACKGROUND: Cardiac contractility modulation (CCM) is an innovative therapy for heart failure with reduced ejection fraction delivered by a cardiac implantable device (Optimizer Smart®). One of the most prominent periprocedural complications common to all cardiac implantable devices (CIDs) is tricuspid regurgitation (TR) due to the placement of the right ventricular endocardial leads. To date, no published studies have assessed the changes in the TR degree in patients with heart failure with reduced ejection fraction (HFrEF) who received an implantable cardioverter-defibrillator (ICD) after the implantation of cardiac contractility modulation therapy devices. OBJECTIVE: This study aimed to evaluate the effect of the implantation of the trans-tricuspid leads required to deliver CCM therapy on the severity of TR in patients with HFrEF who previously underwent ICD implantation. METHODS: We enrolled 30 HFrEF patients who underwent CCM therapy between November 2020 and October 2021. For all the patients, echocardiographic evaluations of TR were performed according to current guidelines 24 h before and six months after the Optimizer Smart® implant was applied. RESULTS: At the 6-month follow-up, the grade of TR remained unchanged compared to the preimplant grade. The value of the vena contracta (VC) of TR was 0.40 ± 0.19 cm in the preimplant period and 0.45 ± 0.21 cm at the 6-month follow-up (p = 0.33). Similarly, the TR proximal isovelocity surface area (PISA) radius value was unchanged at follow-up (0.54 ± 0.22 cm vs. 0.62 ± 0.20 cm; p = 0.18). No statistically significant difference existed between the preimplant VC and PISA radius values, irrespective of the device type. CONCLUSIONS: The implantation of right ventricular electrodes for the delivery of CCM therapy did not worsen tricuspid regurgitation in patients with HFrEF and ICD.

Cardiac contractility modulation therapy improves health status in patients with heart failure with preserved ejection fraction: a pilot study (CCM-HFpEF).

AIMS: This pilot study aimed to assess the potential benefits of cardiac contractility modulation (CCM) in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: This was a prospective, multicentre, single-arm, pilot study of CCM therapy in patients with HFpEF and New York Heart Association (NYHA) class II or III. Echocardiographic parameters were measured by an echo core laboratory to determine study eligibility. After CCM device implantation, patients were followed for 24 weeks. Overall, 47 patients (mean age 74.3 ± 4.4 years, 70.2% female) were enrolled, with left ventricular ejection fraction of 59 ± 4.4%, 63.8% with hypertension, 46.8% with atrial fibrillation, 40.4% with diabetes, 31.9% with at least one heart failure hospitalization in the prior year, 61.7% in NYHA class III, and Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score of 48.9 ± 21.7. The primary efficacy endpoint (mean change in the KCCQ overall summary score) improved by 18.0 ± 16.6 points (p < 0.001) and there was an event-free rate of 93.6% for the primary safety endpoint (device- and procedure-related complications), as adjudicated by an independent physician committee. CONCLUSION: This pilot study demonstrates that the benefits of CCM may extend to the HFpEF patient population. The significant improvement in health status observed, with no obvious impact on safety, suggests that utilization of CCM for patients with HFpEF could prove to be promising.

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.

Cardiac contractility modulation for the treatment of moderate to severe HF.

Introduction: Heart failure (HF) affects over 6 million Americans and approximately 650,000 new cases are diagnosed annually, with patients evenly split between HFrEF and HFpEF. Recent advances in therapy for these patients have been limited to pharmaceutical agents, with CRT remaining the most reliable device therapy option since its advent almost twenty years ago. In 2019, after almost two decades without the introduction of a new device therapy for the treatment of moderate HF, the FDA approved CCM® therapy, delivered by the Optimizer Smart device, for patients with NYHA Class III HF who are on guideline-directed medical therapy (GDMT), in normal sinus rhythm (NSR), and with EF ranging from 25% to 45%, and who are ineligible for CRT.Areas covered: Multiple clinical trials support the use of CCM to improve quality of life, functional class, and 6-min hall walk distance. This article will discuss the science behind CCM therapy, the presumed mechanisms of action, the pre-clinical studies that shaped subsequent endeavors, and the clinical trials that support its use.Expert opinion: The introduction of CCM therapy bridges a therapeutic gap for patients with few or no other therapeutic options for NYHA III heart failure.

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.