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Randomized Controlled Trial
. 2024 Oct 1;9(10):871-879.
doi: 10.1001/jamacardio.2024.2050.

Leadless Ultrasound-Based Cardiac Resynchronization System in Heart Failure

Jagmeet P Singh  1 , Christopher A Rinaldi  2   3 , Prashanthan Sanders  4 , Spencer H Kubo  5 , Simon James  6 , Imran K Niazi  7 , Timothy Betts  8 , Christian Butter  9 , Toshimasa Okabe  10 , Ryan Cunnane  11 , Emad Aziz  12 , Mauro Biffi  13 , Amir Zaidi  14 , Jeffrey Alison  15 , Pascal Defaye  16 , Angelo Aurrichio  17 , Michael R Gold  18 , JoAnn Lindenfeld  19 , Tyson Rogers  20 , Mary Norine Walsh  21 ; SOLVE-CRT Investigators
Affiliations
Randomized Controlled Trial

Leadless Ultrasound-Based Cardiac Resynchronization System in Heart Failure

Jagmeet P Singh et al. JAMA Cardiol. .

Abstract

Importance: Approximately 40% of patients with heart failure (HF) who are eligible for cardiac resynchronization therapy (CRT) either fail to respond or are untreatable due to anatomical constraints.

Objective: To assess the safety and efficacy of a novel, leadless, left ventricular (LV) endocardial pacing system for patients at high risk for a CRT upgrade or whose coronary sinus (CS) lead placement/pacing with a conventional CRT system failed.

Design, setting, and participants: The SOLVE-CRT study was a prospective multicenter trial enrolling January 2018 through July 2022, with follow-up at 6 months. Data were analyzed from January 17, 2018, through February 15, 2023. The trial combined data from an initial randomized, double-blind study (n = 108) and a subsequent single-arm part (n = 75). It took place at 36 centers across Australia, Europe, and the US. Participants were nonresponders, previously untreatable (PU), or high-risk upgrades (HRU). All participants contributed to the safety analysis. The primary efficacy analysis (n = 100) included 75 PU-HRU patients from the single-arm part and 25 PU-HRU patients from the randomized treatment arm.

Interventions: Patients were implanted with the WiSE CRT System (EBR Systems) consisting of a leadless LV endocardial pacing electrode stimulated with ultrasound energy delivered by a subcutaneously implanted transmitter and battery.

Main outcomes and measures: The primary safety end point was freedom from type I complications. The primary efficacy end point was a reduction in mean LV end systolic volume (LVESV).

Results: The study included 183 participants; mean age was 68.1 (SD, 10.3) years and 141 were male (77%). The trial was terminated at an interim analysis for meeting prespecified stopping criteria. In the safety population, patients were either New York Heart Association Class II (34.6%) or III (65.4%). The primary efficacy end point was met with a 16.4% (95% CI, -21.0% to -11.7%) reduction in mean LVESV (P = .003). The primary safety end point was met with an 80.9% rate of freedom from type I complications (P < .001), which included 12 study device system events (6.6%), 5 vascular events (2.7%), 3 strokes (1.6%), and 7 cardiac perforations which mostly occurred early in the study (3.8%).

Conclusions and relevance: The SOLVE-CRT study has demonstrated that leadless LV endocardial pacing with the WiSE CRT system is associated with a reduction in LVESV in patients with HF. This novel system may represent an alternative to conventional CRT implants in some HF patient populations.

Trial registration: ClinicalTrials.gov Identifier: NCT0292203.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Singh reported personal fees from EBR Systems during the conduct of the study; consultant fees from Abbott, Boston Scientific, Biotronik, Cardiologs, EBR, CVRx, Impulse Dynamics, Implicity, I-Rhythm, Medtronic, Medscape, Microport, Notal Vision, Orchestr Bio-Med, BioTel (Phillips), Sanofi, SmartCardia, and VektorMedical outside the submitted work. Dr Rinaldi reported grants, honoraria, speakers fees, steering committee membership, research funding, and personal fees from EBR Systems outside the submitted work. Dr Sanders reported fees from EBR Systems during the conduct of the study; advisory board research grants from Medtronic, Abbott, Boston-Scientific, Becton Dickenson, Pacemate, and CathRx outside the submitted work; and was supported by an investigator grant from the National Health and Medical Research Council of Australia. Dr Kubo reported consultant from EBR Systems during the conduct of the study. Dr Niazi reported grants from Aurora Healthcare fees for recruiting patients for study during the conduct of the study. Dr Betts reported personal fees from EBR Solutions during the conduct of the study. Dr Okabe reported personal fees from Abbott outside the submitted work. Dr Aziz reported grants from research part of the study during the conduct of the study. Dr Auricchio reported personal fees from EBR System, fees from Boston Scientific for participation in clinical trials, and consultancy fees from Medtronic and Philips during the conduct of the study; in addition, Dr Auricchio had a patent issued from Boston Scientific, Microport, and Biosense Webster. Dr Gold reported personal fees from Boston Scientific, Medtronic, and EBR outside the submitted work. Dr Lindenfeld reported personal fees from Abbott, Edwards, Boston Scientific, and Medtronic during the conduct of the study, personal fees and grants from AstraZenca, personal fees from Axon, Alleviant, WhiteSwell, CVRx, VWave, and Vascular Dynamics outside the submitted work. Dr Rogers reported fees EBR Systems during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. WiSE Cardiac Resynchronization Therapy (CRT) System
Existing co-implant device (pacemaker, implantable cardioverter defibrillator of CRT) providing right ventricular pacing (A); the receiver-electrode converts ultrasound into electrical energy to pace the LV from the endocardium (B); the battery powers the transmitter; implanted subcutaneously at the left midaxillary line (C); the phase array transmitter that is synchronized with right ventricular pacing pulse and transmits ultrasound energy to the receiver-electrode (D).
Figure 2.
Figure 2.. Modified Study Design and Patient Disposition at 6 Months
Part 2, randomization phase, was suspended in March 2020 due to the COVID-19 pandemic with 108 patients enrolled. To accommodate COVID-19 restrictions, the single-arm part (part 3) was instituted, and the inclusion criteria no longer included nonresponders. Twenty-five patients from part 2 were in the treatment arm subset of previously untreatable or high-risk upgrade patients. Seventy-five patients were enrolled in part 3, single arm. The safety population includes all patients enrolled in part 2 and part 3, while the efficacy population includes all patients enrolled in part 3 plus the subset of part 2 matching the indication. aNot included in the analysis.
Figure 3.
Figure 3.. Percent Change in Left Ventricular End Systolic Volume (LVESV) at 6 Months vs Performance Goal and LVESV, Left Ventricular End Diastolic Volume (LVEDV), and Left Ventricular Ejection Fraction (LVEF) Baseline vs 6-Month Follow-Up
A, The intent-to-treat change in LVESV of −16.4% is shown. The upper boundary of the 2-sided 95% CI was used as the cutoff for meeting the prespecified efficacy objective. aThe P value is based on a 1-sample t test. bThe nominal P values are based on paired t tests comparing 6 months with baseline values for LVESV (mL), LVEDV (mL), and LVEF (%). These nominal P values are not adjusted for multiplicity.
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Comment on

References

    1. Abraham WT, Fisher WG, Smith AL, et al. ; MIRACLE Study Group. Multicenter InSync Randomized Clinical Evaluation . Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002;346(24):1845-1853. doi:10.1056/NEJMoa013168 - DOI - PubMed
    1. Cleland JG, Daubert JC, Erdmann E, et al. ; Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators . The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005;352(15):1539-1549. doi:10.1056/NEJMoa050496 - DOI - PubMed
    1. McAlister FA, Ezekowitz J, Hooton N, et al. . Cardiac resynchronization therapy for patients with left ventricular systolic dysfunction: a systematic review. JAMA. 2007;297(22):2502-2514. doi:10.1001/jama.297.22.2502 - DOI - PubMed
    1. Bristow MR, Saxon LA, Boehmer J, et al. ; Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) Investigators . Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004;350(21):2140-2150. doi:10.1056/NEJMoa032423 - DOI - PubMed
    1. Rivero-Ayerza M, Theuns DA, Garcia-Garcia HM, Boersma E, Simoons M, Jordaens LJ. Effects of cardiac resynchronization therapy on overall mortality and mode of death: a meta-analysis of randomized controlled trials. Eur Heart J. 2006;27(22):2682-2688. doi:10.1093/eurheartj/ehl203 - DOI - PubMed