BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) has demonstrated safety and efficacy for the treatment of malignant ventricular arrhythmias. However, a limitation of the S-ICD lies in the inability to either pace-terminate ventricular tachycardia or provide prolonged bradycardia pacing support. OBJECTIVE: The rationale and design of a prospective, single-arm, multinational trial of an intercommunicative leadless pacing system integrated with the S-ICD will be presented. METHODS: A technical description of the modular cardiac rhythm management (mCRM) system (EMPOWER leadless pacemaker and EMBLEM S-ICD) and the implantation procedure is provided. MODULAR ATP (Effectiveness of the EMPOWER™ Modular Pacing System and EMBLEM™ Subcutaneous ICD to Communicate Antitachycardia Pacing) is a multicenter, international trial enrolling up to 300 patients at risk of sudden cardiac death at up to 60 centers trial design. The safety endpoint of freedom from major complications related to the mCRM system or implantation procedure at 6 months and 2 years are significantly higher than 86% and 81%, respectively, and all-cause survival is significantly >85% at 2 years. RESULTS: Efficacy endpoints are that at 6 months mCRM communication success is significantly higher than 88% and the percentage of subjects with low and stable thresholds is significantly higher than 80%. Substudies to evaluate rate-responsive features and performance of the pacing module are also described. CONCLUSION: The MODULAR ATP global clinical trial will prospectively test the safety and efficacy of the first intercommunicating leadless pacing system with the S-ICD. This trial will allow for robust validation of device-device communication, pacing performance, rate responsiveness, and system safety.

Boston Scientific Corporation St Paul Minnesota

Cardiac Electrophysiology Drexel University Philadelphia Pennsylvania

Cardiac Rhythm Management Research Department University Hospital Southampton NHS Foundation Trust Southampton United Kingdom

Cardiology Division Azienda Ospedaliero Universitaria Pisana Pisa Italy

College of Medicine University of Arizona Phoenix Arizona

CorVita Science Foundation Chicago Illinois

Departement de Cardiologie Hôpital Privé du Confluent Nantes France

Department of Cardiology Amsterdam University Medical Center Amsterdam the Netherlands

Department of Cardiology Liverpool Heart and Chest Hospital Liverpool United Kingdom

Department of Cardiology Na Homolce Hospital Prague Czech Republic

Department of Cardiology Saint Mary Medical Center Langhorne Pennsylvania

Department of Cardiology St Antonius Hospital Nieuwegein the Netherlands

Department of Cardiovascular Medicine Mayo Clinic Rochester Minnesota

Department of Medical Sciences Cardiology Arrhythmia Uppsala University Uppsala Sweden

Heart and Vascular Health HonorHealth Research Institute Scottsdale Arizona

Heart and Vascular Institute Cleveland Clinic Cleveland Ohio

Hospital Clínic Universitat de Barcelona Barcelona Spain

Icahn School of Medicine Mount Sinai New York New York

Institut de Recerca Biomèdica August Pi i Sunyer Biomedical Research Institute Barcelona Spain

School of Medical Sciences Faculty of Medicine and Health Örebro University Örebro Sweden

School of Medicine Emory University Atlanta Georgia

See more in PubMed

Knops R.E., Olde Nordkamp L.R.A., Delnoy P.H.M., et al. Subcutaneous or transvenous defibrillator therapy. N Engl J Med. 2020;383:526–536. PubMed

Healey J.S., Krahn A.D., Bashir J., et al. Perioperative safety and early patient and device outcomes among subcutaneous versus transvenous implantable cardioverter defibrillator implantations: a randomized, multicenter trial. Ann Intern Med. 2022;175:1658–1665. PubMed

Weiss R., Knight B.P., Gold M.R., et al. Safety and efficacy of a totally subcutaneous implantable-cardioverter defibrillator. Circulation. 2013;128:944–953. PubMed

Lambiase P.D., Theuns D.A., Murgatroyd F., et al. Subcutaneous implantable cardioverter-defibrillators: long-term results of the EFFORTLESS study. Eur Heart J. 2022;43:2037–2050. PubMed PMC

Gold M.R., Lambiase P.D., El-Chami M.F., et al. Primary results from the Understanding Outcomes With the S-ICD in Primary Prevention Patients With Low Ejection Fraction (UNTOUCHED) trial. Circulation. 2021;143:7–17. PubMed PMC

Burke M.C., Aasbo J.D., El-Chami M.F., et al. 1-Year prospective evaluation of clinical outcomes and shocks: the Subcutaneous ICD Post Approval Study. J Am Coll Cardiol EP. 2020;6:1537–1550. PubMed

Al-Khatib S.M., Stevenson W.G., Ackerman M.J., et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2018;72:e91–e220. PubMed

Brisben A.J., Burke M.C., Knight B.P., et al. A new algorithm to reduce inappropriate therapy in the S-ICD system. J Cardiovasc Electrophysiol. 2015;26:417–423. PubMed

Theuns D., Brouwer T.F., Jones P.W., et al. Prospective blinded evaluation of a novel sensing methodology designed to reduce inappropriate shocks by the subcutaneous implantable cardioverter-defibrillator. Heart Rhythm. 2018;15:1515–1522. PubMed

Huang J., Patton K.K., Prutkin J.M. Concomitant use of the subcutaneous implantable cardioverter defibrillator and a permanent pacemaker. Pacing Clin Electrophysiol. 2016;39:1240–1245. PubMed

Ljungstrom E., Brandt J., Mortsell D., Borgquist R., Wang L. Combination of a leadless pacemaker and subcutaneous defibrillator with nine effective shock treatments during follow-up of 18 months. J Electrocardiol. 2019;56:1–3. PubMed

Ahmed F.Z., Cunnington C., Motwani M., Zaidi A.M. Totally leadless dual-device implantation for combined spontaneous ventricular tachycardia defibrillation and pacemaker function: a first report. Can J Cardiol. 2017;33(1066):e1065–e1066.e7. PubMed

Ito R., Kondo Y., Winter J., et al. Combination of a leadless pacemaker and subcutaneous implantable cardioverter defibrillator therapy for a Japanese patient with prosthetic valve endocarditis. J Arrhythm. 2019;35:311–313. PubMed PMC

Breeman K.T.N., Swackhamer B., Brisben A.J., et al. Long-term performance of a novel communicating antitachycardia pacing-enabled leadless pacemaker and subcutaneous implantable cardioverter-defibrillator system: A comprehensive preclinical study. Heart Rhythm. 2022;19:837–846. PubMed

Tjong F.V.Y., Brouwer T.F., Koop B., et al. Acute and 3-month performance of a communicating leadless antitachycardia pacemaker and subcutaneous implantable defibrillator. J Am Coll Cardiol EP. 2017;3:1487–1498. PubMed

Habib G., Lancellotti P., Antunes M.J., et al. 2015 ESC guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM) Eur Heart J. 2015;36:3075–3128. PubMed

Wathen M. Implantable cardioverter defibrillator shock reduction using new antitachycardia pacing therapies. Am Heart J. 2007;153:44–52. PubMed

Wilkoff B.L., Fauchier L., Stiles M.K., et al. 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing. Heart Rhythm. 2016;13:e50–e86. PubMed

Stiles M.K., Fauchier L., Morillo C.A., Wilkoff B.L. 2019 HRS/EHRA/APHRS/LAHRS focused update to 2015 expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing. J Interv Card Electrophysiol. 2020;59:135–144. PubMed PMC

Reddy V.Y., Exner D.V., Cantillon D.J., et al. Percutaneous implantation of an entirely intracardiac leadless pacemaker. N Engl J Med. 2015;373:1125–1135. PubMed

Ritter P., Duray G.Z., Zhang S., et al. Micra Transcatheter Pacing Study Group. The rationale and design of the Micra Transcatheter Pacing Study: safety and efficacy of a novel miniaturized pacemaker. Europace. 2015;17:807–813. PubMed

Kay G.N. Quantitation of chronotropic response: comparison of methods for rate-modulating permanent pacemakers. J Am Coll Cardiol. 1992;20:1533–1541. PubMed

Wilkoff B.L., Corey J., Blackburn G. A mathematical model of the cardiac chronotropic response to exercise. J Electrophysiol. 1989;3:176–180.

Medicines and Healthcare products Regulatory Agency Leadless cardiac pacemaker therapy: design of pre- and post-market clinical studies. 2021. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/956252/Leadless-EAG-guidance.pdf Available at:

Lawton J.S., Wood M.A., Gilligan D.M., Stambler B.S., Damiano R.J., Jr., Ellenbogen K.A. Implantable transvenous cardioverter defibrillator leads: the dark side. Pacing Clin Electrophysiol. 1996;19:1273–1278. PubMed

Hauser R.G., McGriff D., Retel L.K. Riata implantable cardioverter-defibrillator lead failure: analysis of explanted leads with a unique insulation defect. Heart Rhythm. 2012;9:742–749. PubMed

Krahn A.D., Champagne J., Healey J.S., et al. Outcome of the Fidelis implantable cardioverter-defibrillator lead advisory: a report from the Canadian Heart Rhythm Society Device Advisory Committee. Heart Rhythm. 2008;5:639–642. PubMed

Reynolds D., Duray G.Z., Omar R., et al. A leadless intracardiac transcatheter pacing system. N Engl J Med. 2016;374:533–541. PubMed

Friedman P., Murgatroyd F., Boersma L.V.A., et al. Efficacy and safety of an extravascular implantable cardioverter-defibrillator. N Engl J Med. 2022;387:1292–1302. PubMed

Schron E.B., Exner D.V., Yao Q., et al. Quality of life in the antiarrhythmics versus implantable defibrillators trial: impact of therapy and influence of adverse symptoms and defibrillator shocks. Circulation. 2002;105:589–594. PubMed

Larsen G.K., Evans J., Lambert W.E., Chen Y., Raitt M.H. Shocks burden and increased mortality in implantable cardioverter-defibrillator patients. Heart Rhythm. 2011;8:1881–1886. PubMed

Knops R.E., van der Stuijt W., Delnoy P., et al. Efficacy and safety of appropriate shocks and antitachycardia pacing in transvenous and subcutaneous implantable defibrillators: analysis of all appropriate therapy in the PRAETORIAN trial. Circulation. 2022;145:321–329. PubMed

Schuger C.D., Ando K., Cantillon D.J., et al. Assessment of primary prevention patients receiving an ICD - Systematic evaluation of ATP: APPRAISE ATP. Heart Rhythm O2. 2021;2:405–411. PubMed PMC

Arenal A., Proclemer A., Kloppe A., et al. Different impact of long-detection interval and anti-tachycardia pacing in reducing unnecessary shocks: data from the ADVANCE III trial. Europace. 2016;18:1719–1725. PubMed PMC

Schuger C., Daubert J.P., Zareba W., et al. Reassessing the role of antitachycardia pacing in fast ventricular arrhythmias in primary prevention implantable cardioverter-defibrillator recipients: results from MADIT-RIT. Heart Rhythm. 2021;18:399–403. PubMed

Wathen M.S., DeGroot P.J., Sweeney M.O., et al. PainFREE Rx III Trial Investigators. Prospective randomized multicenter trial of empirical antitachycardia pacing versus shocks for spontaneous rapid ventricular tachycardia in patients with implantable cardioverter-defibrillators: Pacing Fast Ventricular Tachycardia Reduces Shock Therapies (PainFREE Rx II) trial results. Circulation. 2004;110:2591–2596. PubMed

Moss A.J., Schuger C., Beck C.A., et al. Reduction in inappropriate therapy and mortality through ICD programming. N Engl J Med. 2012;367:2275–2283. PubMed

Della Bella P., Baratto F., Vergara P., et al. Does timing of ventricular tachycardia ablation affect prognosis in patients with an implantable cardioverter defibrillator? results from the multicenter randomized PARTITA trial. Circulation. 2022;145:1829–1838. PubMed