Integra-D: Combination CCM & Defibrillator Successful in Treating HFrEF

A novel Cardiac Contractility Modulation Defibrillator (CCM-D) has provided an integrated therapy for patients with heart failure with reduced ejection fraction (HFrEF), according to data from the Integra-D trial.1

Presented at the Heart Failure Society of America Annual Scientific Meeting 2025 in Minneapolis, MN, by Niraj Varma, MA, MD, PhD, an electrophysiologist at Cleveland Clinic, and colleagues, these data highlight the efficacy and safety of this combination modulator and defibrillator. The device functions via a 2-battery system; one is a rechargeable battery to deliver daily CCM therapy, and the other is non-rechargeable and delivers high-voltage implantable cardioverter-defibrillator (ICD) therapy and antitachycardia pacing, as well as post-shock brady pacing and emergent brady pacing.1

The Integra-D trial aimed to prove the device’s efficacy in converting induced VF at implant in 100 consecutive patients. Additionally, the trial’s safety assessment included 1 month per-procedural complications, including invasive intervention, major medical intervention, hospitalization, or mortality. The implant would also be judged based on a 6-month New York Heart Association (NYHA) assessment.1

Investigators selected patients indicated for de novo ICD without CRT, stage C/D HF on guideline-directed medical therapy (GDMT) and left ventricular ejection fraction (LVEF) ≤40%. Standard implant techniques were used, with the generator placed on the pectoral and the DF-4 and 15-1 leads in the right ventricular septum. Patients then underwent defibrillation efficacy testing – if ≥96 out of 100 tests were successes, the primary endpoint would be met.1,2

Investigators would then conduct a follow-up phase, which lasted until the last subject enrolled completes their 6-month visit, at which time they would take a 6-month NYHA assessment for comparison to baseline.1,2

Ultimately, the team enrolled a total of 101 patients. Of these, 45.5% were noted as Class II by the NYHA system, 47.5% were Class III, and 1% were Class IV. Participants had a mean age of 62.5 years and a mean BMI of 29.3 kg/m2. 81.2% of patients had hypertension, 47.5% had diabetes, 79.2% had dyslipidemia, and 24.8% had chronic kidney disease (CKD) ≥ Stage 3. Mean LVEF among included patients was 30%. 14.9% had atrial fibrillation and 52.5% had ischemic cardiomyopathy.1

Among the 101 patients, 53.5% were on ≥triple therapy for HF, with 35.6% on quad therapy including a sodium-glucose co-transporter 2 inhibitor. The most commonly used individual HF medication was beta blockers (82%), followed by angiotensin receptors/neprilysin inhibitors (55%) and mineralocorticoid receptor agonists (55%).1

The acute defibrillation efficacy testing was conducted via ≤2 shocks, with the first set to 26 J and the second at 36 J. If ventricular arrhythmia continued after this test, external rescue was performed, DF-4 was repositioned, and the test was conducted again.1

Ultimately, investigators noted a total of 100 successful ventricular arrhythmia conversions – 2 patients initially failed, with 1 successfully converting after readmission and 1 removed as non-inducible. 100% of patients ultimately received successful DE tests (95% CI, 96.4%-100%; P <.001). The team recorded a success rate of 94/100 for the first shock and 6/6 for the second. Additionally, 94% of subjects succeeded with DF-4 placement in the right ventricular septum.1

At the end of the 6-month follow-up, the team found 88% of patients improved or remained stable, while 7% improved by 2 classes. Class III patients exhibited the largest improvement, while Class II patients had more modest improvements, indicating a possible ceiling effect. Of the 11 remaining patients who worsened, 6 had frequent charging noncompliance or adverse events near the 6-month NYHA assessment period.1

“CCM-D provides an integrated therapy for the HFrEF patient, offering both symptom relief and sudden cardiac death prevention,” wrote Varma and colleagues.1

References

1. Varma N, Panico A, Baranowski B, et al. Effects of a Novel Cardiac Contractility Modulation-Defibrillator (CCM-D) on NYHA Functional Class in ICD-Indicated Patients. Presented at the Heart Failure Society of America Annual Scientific Meeting 2025. Minneapolis, MN. September 26-29, 2025.

2. Impulse Dynamics. Assessment of Combined CCM and ICD Device in HFrEF (INTEGRA-D). ClinicalTrials.gov identifier: NCT05855135. Updated July 31, 2025. Accessed September 28, 2025. https://clinicaltrials.gov/study/NCT05855135