Established and Emerging Device Therapy in Heart Failure: Cardiac Contractility Modulation.
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SUBMITTER: Haloot J
PROVIDER: S-EPMC10751469 | biostudies-literature | 2023 Nov
REPOSITORIES: biostudies-literature
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Established and Emerging Device Therapy in Heart Failure: Cardiac Contractility Modulation.
Haloot Justin J Chelu Mihail G MG
Texas Heart Institute journal 20231101 6
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Project description:(1) Background: Heart failure (HF) is a major cause of morbidity and mortality throughout the world. Despite substantial progress in its prevention and treatment, mortality rates remain high. Device therapy for HF mainly includes cardiac resynchronization therapy (CRT) and the use of an implantable cardioverter-defibrillator (ICD). Recently, however, a new device therapy-cardiac contractility modulation (CCM)-became available. (2) Aim: The purpose of this study is to present a first case-series of patients with different clinical patterns of HF with a reduced ejection fraction (HFrEF), supported with the newest generation of CCM devices. (3) Methods and results: Five patients with a left ventricular ejection fraction (LVEF) ? 35% and a New York Heart Association (NYHA) class ? III were supported with CCM OPTIMIZER® SMART IPGCCMX10 at our clinic. The patients had a median age of 67 ± 8.03 years (47-80) and were all males-four with ischemic etiology dilated cardiomyopathy. In two cases, CCM was added on top of CRT (non-responders), and, in one patient, CCM was delivered during persistent atrial fibrillation (AF). After 6 months of follow-up, the LVEF increased from 25.4 ± 6.8% to 27 ± 9%, and the six-minute walk distance increased from 310 ± 65.1 m to 466 ± 23.6 m. One patient died 47 days after device implantation. (4) Conclusion: CCM therapy provided with the new model OPTIMIZER® SMART IPG CCMX10 is safe, feasible, and applicable to a wide range of patients with HF.
| S-EPMC6572164 | biostudies-literature
Project description:AIMS:The objective of this paper is to assess whether cardiac contractility modulation (via the Optimizer System) plus standard of care (SoC) is a cost-effective treatment for people with heart failure [New York Heart Association (NYHA) III, left ventricular ejection fraction of 25-45%, and narrow QRS] compared against SoC alone from the perspective of the English National Health Service. METHODS AND RESULTS:We developed a regression equation-based cost-effectiveness model, using individual patient data from three randomized control trials (FIX-HF-5 Phases 1 and 2, and FIX-HF-5C) to populate the majority of parameters. A series of regression equations predicted NYHA class over time, mortality, all-cause hospitalization rates, and health-related quality of life. We conducted the analysis in line with the National Institute for Health and Care Excellence reference case, modelling costs from an English National Health Service perspective, and considering outcomes in quality-adjusted life years (QALYs) over a patient lifetime perspective. Our base case analysis produced an incremental cost per additional QALY of GBP22 988 (€25 750) when comparing Optimizer + SoC to SoC alone. This result was not sensitive to parameter uncertainty but was sensitive to the time horizon over which costs and QALYs were captured and the duration over which a survival benefit with Optimizer + SoC can be assumed to apply. CONCLUSIONS:Cardiac contractility modulation is likely to be cost-effective in people with heart failure with reduced ejection fraction, NYHA III, and narrow QRS, provided that the treatment benefit can be maintained beyond the duration of the existing clinical trial follow-up. This analysis supports the current recommendations of the European Society of Cardiology that this therapy may be considered for such patients.
| S-EPMC6989288 | biostudies-literature
Project description: Not available
| S-EPMC9809070 | biostudies-literature
Project description: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. 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. 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.
| S-EPMC7754749 | biostudies-literature
Project description:BackgroundCardiac contractility modulation (CCM) is non-excitatory electrical stimulation for improving cardiac function. This study aimed to evaluate the effects of CCM on autophagy and apoptosis of cardiac myocytes in a rabbit model of chronic heart failure (CHF) and explore its possible mechanism.MethodsThirty rabbits were randomised into the Sham, heart failure (HF) and CCM groups, and animals in all three groups were sacrificed after 16 weeks of ascending aortic constriction or sham surgery. The expression of autophagy associated protein LC3 was observed by immunofluorescence staining. With Western-blot measured the expression of Beclin1, P62, LC3B (II/I) and Bcl-2, ALDH2, Bax and Caspase-3 protein in myocardial tissue. The apoptosis rate and the apoptosis of myocardial cells was observed by flow cytometry and TUNEL method.Results1) In comparison to the Sham group, the expression of LC3 and Beclin1 was significantly increased, and the expression of p62 protein was decreased in the heart tissues of rabbits in the HF group. Compared with HF group, after CCM intervention, the expression of Beclin1 and LC3B proteins decreased, while the P62 protein increased, and the LC3B(II/I) ratio decreased (P<0.05). 2) The expression of Bcl-2, ALDH2 protein and Bcl-2 mRNA decreased compared with the Sham group (P<0.05), while the expression of Bax, Caspase-3 protein and mRNA was significantly increased (P<0.05). However, the expression of ALDH2 mRNA in the CCM group was not statistically significant. The expression of Bcl-2, ALDH2 protein and mRNA increased after CCM intervention, and the expression of Bax, Caspase-3 protein and mRNA decreased (P<0.05). 3) The apoptosis situation in the Sham group was similar to that of normal myocardium, compared with the Sham group, the number of apoptotic bodies increased, and the apoptosis percentage of cardiomyocytes increased significantly (P<0.05). After CCM intervention, the number of apoptotic bodies and the percentage of apoptosis decreased compared with the HF group (P<0.05).ConclusionsThe intervention of CCM has been shown to enhance both myocardial systolic and diastolic function in rabbits with CHF. The mechanism may be related to the inhibition of cardiomyocyte autophagy by regulating the expression levels of Beclin1, P62, and LC3B(II/I) in cardiomyocytes, as well as the reversal of cardiomyocyte apoptosis by regulating the expression levels of Bcl-2, ALDH2, Bax, and Caspase-3 in cardiomyocytes.
| S-EPMC11658494 | biostudies-literature
Project description:AimsThis 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 resultsThis 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.ConclusionThis 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.
| S-EPMC10087783 | biostudies-literature
Project description:BackgroundCardiac contractility modulation (CCM) is an electrical-device therapy for patients with heart failure with reduced ejection fraction (HFrEF). Patients with left ventricular ejection fraction (LVEF) ≤35% also have indication for an implantable cardioverter-defibrillator (ICD), and in some cases subcutaneous ICD (S-ICD) is selected.HypothesisCCM and S-ICD can be combined to work efficaciously and safely.MethodsWe report on 20 patients with HFrEF and LVEF ≤35% who received CCM and S-ICD. To exclude device interference, patients received intraoperative crosstalk testing, S-ICD testing, and bicycle exercise testing while CCM was activated. Clinical and QOL measures before CCM activation and at last follow-up were analyzed. S-ICD performance was evaluated while both CCM and S-ICD were active.ResultsMean follow-up was 34.3 months. NYHA class improved from 2.9 ± 0.4 to 2.1 ± 0.7 (P < 0.0001), Minnesota Living With Heart Failure Questionnaire score improved from 50.2 ± 23.7 to 29.6 ± 22.8 points (P < 0.0001), and LVEF improved from 24.4% ± 8.1% to 30.9% ± 9.6% (P = 0.002). Mean follow-up time with both devices active was 22 months. Three patients experienced a total of 6 episodes of sustained ventricular tachycardia, all successfully treated with first ICD shock. One case received an inappropriate shock unrelated to the concomitant CCM. One patient received an LVAD, so CCM and S-ICD were discontinued.ConclusionsCCM and S-ICD can be successfully combined in patients with HFrEF. S-ICD and CCM remain efficacious when used together, with no interference affecting their function.
| S-EPMC5947638 | biostudies-literature
Project description:We hypothesized that myocardial septal scarring, assessed by cardiac magnetic resonance (CMR) using late gadolinium enhancement (LGE), at the site of cardiac contractility modulation (CCM) lead placement may predict treatment response. Eligible heart failure (HF) patients underwent LGE CMR imaging before CCM device implantation. The response to CCM therapy at follow-up was determined by a change in NYHA class and echocardiographic left ventricular ejection fraction (LVEF) assessment. Patients were classified as responders, if they showed an improvement in either NYHA class or improvement of LVEF by ≥ 5%. 58 patients were included. 67% of patients were classified as responders according to improved NYHA; 55% according to LVEF improvement. 74% of patients were responders if either NYHA class or LVEF improvement was observed. 90% of responders (according to NYHA class) showed septal LGE < 25% at septal position of the leads, while 44% of non-responders showed septal LGE > 25% (p < 0.01). In patients treated with CCM, an improvement of NYHA class was observed when leads were placed at myocardial segments with a CMR- LGE burden less than 25%.
| S-EPMC9705404 | biostudies-literature
Project description:BackgroundIn dogs with heart failure (HF), chronic therapy with cardiac contractility modulation (CCM) electrical signals delivered to left ventricular (LV) muscle during the absolute refractory period improves LV function. This study examined the effects of CCM therapy on the expression of calcium (Ca(2+))-binding proteins (CBPs) in dogs with HF.Methods and resultsStudies were performed in LV tissue from seven CCM-treated HF dogs, seven untreated HF dogs, and six normal (NL) dogs. mRNA expression of S100A1, sorcin, presenillin-1 (PS1), PS2, histidine-rich Ca(2+)-binding protein (HRC), and 18S ribosomal RNA (18S), a housekeeping gene, was measured using RT-PCR. Protein levels of CBPs and calsequestrin (CSQ) were determined by Western blotting. No difference was observed in the expression of 18S and CSQ among study groups. Compared with NL, the expression of S100A1, sorcin, and HRC was decreased, whereas the expression of PS2 was increased in untreated HF dogs. CCM therapy normalized the expression of S100A1, sorcin, and PS2 but not of HRC. No change was seen in the expression of PS1 among study groups.ConclusionCCM therapy restores LV expression of S100A1, PS2, and sorcin. Normalization of CBPs may partly contribute to improved LV function in HF following CCM therapy.
| S-EPMC5350733 | biostudies-literature
Project description:Proof-of-concept to determine the direct biomechanical effects of cardiac contractility modulation (CCM) on living myocardial slices (LMS) from patients with end-stage heart failure (HF). Left ventricular LMS from patients with end-stage HF were produced and cultured in a biomimetic system with mechanical loading and electrical stimulation. CCM stimulation (80 mA, 40 ms delay, 21 ms duration) enhanced maximum contractile force (CCM: 1229 µN (587-2658) vs. baseline: 1066 µN (529-2128), p = 0.05) and area under the contractile curve (CCM: 297 (151-562) vs. baseline: 243 (129-464), p = 0.05) but did not significantly impact contractile duration, time to peak, or time to relaxation. Increasing CCM stimulation delay, duration, and amplitude resulted in a higher fraction of LMS with a positive inotropic response. Furthermore, CCM attenuated the negative force-frequency relationship in HF-LMS. CCM stimulation enhanced contractile force in HF-LMS. The fraction of LMS exerting a positive inotropic response to CCM increased with increasing delay, duration, and amplitude settings, suggesting that personalizing stimulation parameters could optimize the beneficial effects of CCM. CCM is a novel device-based therapy that may improve contractile function, ejection fraction, functional outcomes, and quality of life in patients with heart failure. However, continuous efforts are needed to identify true responders to CCM therapy, understand the exact mechanisms, and optimize the contractile response to CCM stimulation. The present study revealed that CCM enhanced the contractile force of HF-LMS in a stimulation setting-dependent manner, reaching a larger fraction of the myocardium while increasing delay, duration, and amplitude. This understanding may contribute to the individualization of CCM stimulation settings.
| S-EPMC11851609 | biostudies-literature