Programmed Ventricular Stimulation as an Additional Primary Prevention Risk Stratification Tool in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Study

Circulation, vol. 146, pp. 1434–1443

Abstract

Background: A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value. Methods: All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period. Results: Two hundred eighty-eight patients (41.0±14.5 years, 55.9% male, right ventricular ejection fraction 42.5±11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89–10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA ( P <0.001). Inducible ventricular tachycardia predicted clinical sustained VA during the 5-year follow-up and remained an independent predictor after accounting for the calculator-predicted risk (HR, 2.52 [1.58–4.02]; P <0.001). Compared with ARVC risk calculator predictions in isolation (C-statistic 0.72), addition of PVS inducibility showed improved prediction of VA events (C-statistic 0.75; log-likelihood ratio for nested models, P <0.001). PVS inducibility had a 76% [67–84] sensitivity and 68% [61–74] specificity, corresponding to log-likelihood ratios of 2.3 and 0.36 for inducible (likelihood ratio+) and noninducible (likelihood ratio–) patients, respectively. In patients with a ARVC risk calculator–predicted risk of clinical VA events <25% during 5 years (ie, low/intermediate subgroup), PVS had a 92.6% negative predictive value. Conclusions: PVS significantly improved risk stratification above and beyond the calculator-predicted risk of VA in a primary prevention cohort of patients with ARVC, mainly for patients considered to be at low and intermediate risk by the clinical risk calculator.

Authors 31

1. Alessio Gasperetti

   Johns Hopkins University · Johns Hopkins Medicine · Johns Hopkins Hospital

   Affiliation as printed

   Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (A.G., R.T.C., C. Tichnell, B.M., H.T., H.C., C.A.J.)

   Alessio Gasperetti Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (A.G., R.T.C., C. Tichnell, B.M., H.T., H.C., C.A.J.)

2. Richard T. Carrick

   Johns Hopkins University · Johns Hopkins Medicine · Johns Hopkins Hospital

   Affiliation as printed

   Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (A.G., R.T.C., C. Tichnell, B.M., H.T., H.C., C.A.J.)

   Richard T. Carrick https://orcid.org/0000-0001-5589-1216 Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (A.G., R.T.C., C. Tichnell, B.M., H.T., H.C., C.A.J.)

3. Sarah Costa

   University of Zurich · University Hospital Zurich

   Affiliation as printed

   Department of Cardiology, University Heart Center Zurich, University Hospital Zurich‚ Switzerland (S.C., C.B.B., F.D., A.M.S.)

   Sarah Costa https://orcid.org/0000-0002-7645-6739 Department of Cardiology, University Heart Center Zurich, University Hospital Zurich' Switzerland (S.C., C.B.B., F.D., A.M.S.)

4. Paolo Compagnucci

   Azienda Ospedaliero-Universitaria delle Marche

   Affiliation as printed

   Cardiology and Arrhythmology Clinic, University Hospital Umberto-I-Salesi-Lancisi, Ancona, Italy (P.C., A.D.R., M. Casella)

   Paolo Compagnucci https://orcid.org/0000-0003-1924-6548 Cardiology and Arrhythmology Clinic, University Hospital Umberto-I-Salesi-Lancisi, Ancona, Italy (P.C., A.D.R., M. Casella)

5. Laurens P. Bosman

   Utrecht University · University Medical Center Utrecht

   Affiliation as printed

   Department of Cardiology (L.P.B., A.S.J.M.t.R.), University Medical Center Utrecht, University of Utrecht, The Netherlands

   Laurens P. Bosman https://orcid.org/0000-0002-7847-4607 Department of Cardiology (L.P.B., A.S.J.M.t.R.), University Medical Center Utrecht, University of Utrecht, The Netherlands

6. Monica Chivulescu

   Oslo University Hospital · University of Oslo

   Affiliation as printed

   ProCardio Center for Innovation, Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway and University of Oslo (M. Chivulescu, K.H.H.)

   Monica Chivulescu ProCardio Center for Innovation, Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway and University of Oslo (M. Chivulescu, K.H.H.)

7. Crystal Tichnell

   Johns Hopkins University · Johns Hopkins Medicine · Johns Hopkins Hospital

   Affiliation as printed

   Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (A.G., R.T.C., C. Tichnell, B.M., H.T., H.C., C.A.J.)

   Crystal Tichnell Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (A.G., R.T.C., C. Tichnell, B.M., H.T., H.C., C.A.J.)

8. Brittney A. Murray

   Johns Hopkins University · Johns Hopkins Medicine · Johns Hopkins Hospital

   Affiliation as printed

   Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (A.G., R.T.C., C. Tichnell, B.M., H.T., H.C., C.A.J.)

   Brittney Murray https://orcid.org/0000-0001-7870-8584 Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (A.G., R.T.C., C. Tichnell, B.M., H.T., H.C., C.A.J.)

9. Harikrishna S. Tandri

   Johns Hopkins University · Johns Hopkins Medicine · Johns Hopkins Hospital

   Affiliation as printed

   Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (A.G., R.T.C., C. Tichnell, B.M., H.T., H.C., C.A.J.)

   Harikrishna Tandri https://orcid.org/0000-0003-2651-4352 Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (A.G., R.T.C., C. Tichnell, B.M., H.T., H.C., C.A.J.)

10. Rafik Tadros

    Montreal Heart Institute · Université de Montréal

    Affiliation as printed

    Cardiovascular Genetics Center and Electrophysiology Service, Montreal Heart Institute, Université de Montréal, Canada (R.T., L.R., P.K., J.C.-T.)

11. Léna Rivard

    Montreal Heart Institute · Université de Montréal

    Affiliation as printed

    Cardiovascular Genetics Center and Electrophysiology Service, Montreal Heart Institute, Université de Montréal, Canada (R.T., L.R., P.K., J.C.-T.)

12. Maarten P. van den Berg

    University Medical Center Groningen · University of Groningen

    Affiliation as printed

    Department of Cardiology, University Medical Center Groningen, University of Groningen‚ The Netherlands (M.P.v.d.B.)

    Maarten P. van den Berg https://orcid.org/0000-0002-1493-2998 Department of Cardiology, University Medical Center Groningen, University of Groningen' The Netherlands (M.P.v.d.B.)

13. Katja Zeppenfeld Aachen Department of Cardiology, Leiden University Medical Center

    Leiden University Medical Center

    Affiliation as printed

    Department of Cardiology, Leiden University Medical Center, The Netherlands (K.Z.)

    Katja Zeppenfeld https://orcid.org/0000-0002-7034-1017 Department of Cardiology, Leiden University Medical Center, The Netherlands (K.Z.)

14. Arthur A.M. Wilde

    Amsterdam UMC Location University of Amsterdam

    Affiliation as printed

    Amsterdam UMC location University of Amsterdam‚ Department of Cardiology‚ Amsterdam‚ The Netherlands (A.A.M.W.)

    Arthur A.M. Wilde https://orcid.org/0000-0002-0528-0852 Amsterdam UMC location University of Amsterdam' Department of Cardiology' Amsterdam' The Netherlands (A.A.M.W.)

15. Giulio Pompilio
    Affiliation as printed

    Giulio Pompilio

16. Corrado Carbucicchio

    Centro Cardiologico Monzino

    Affiliation as printed

    Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Department of Clinical Electrophisiology and Cardiac Pacing, Milan, Italy (C.C., C. Tondo)

    Corrado Carbucicchio Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Department of Clinical Electrophisiology and Cardiac Pacing, Milan, Italy (C.C., C. Tondo)

17. Antonio Dello Russo
    Affiliation as printed

    Cardiology and Arrhythmology Clinic, University Hospital Umberto-I-Salesi-Lancisi, Ancona, Italy (P.C., A.D.R., M. Casella)

    Antonio Dello Russo Cardiology and Arrhythmology Clinic, University Hospital Umberto-I-Salesi-Lancisi, Ancona, Italy (P.C., A.D.R., M. Casella)

18. Michela Casella
    Affiliation as printed

    Cardiology and Arrhythmology Clinic, University Hospital Umberto-I-Salesi-Lancisi, Ancona, Italy (P.C., A.D.R., M. Casella)

    Michela Casella Cardiology and Arrhythmology Clinic, University Hospital Umberto-I-Salesi-Lancisi, Ancona, Italy (P.C., A.D.R., M. Casella)

19. Anneli Svensson

    Linköping University

    Affiliation as printed

    Department of Cardiology and Department of Health‚ Medicine and Caring Sciences‚ Linköping University‚ Sweden (A.S.)

20. Corinna Brunckhorst

    University of Zurich · University Hospital Zurich

    Affiliation as printed

    Department of Cardiology, University Heart Center Zurich, University Hospital Zurich‚ Switzerland (S.C., C.B.B., F.D., A.M.S.)

    Corinna B. Brunckhorst Department of Cardiology, University Heart Center Zurich, University Hospital Zurich' Switzerland (S.C., C.B.B., F.D., A.M.S.)

21. J. Peter van Tintelen

    Utrecht University · University Medical Center Utrecht

    Affiliation as printed

    Department of Genetics (J.P.v.T.), University Medical Center Utrecht, University of Utrecht, The Netherlands

    J. Peter van Tintelen https://orcid.org/0000-0003-3854-6749 Department of Genetics (J.P.v.T.), University Medical Center Utrecht, University of Utrecht, The Netherlands

22. Pyotr G. Platonov

    Lund University

    Affiliation as printed

    Department of Cardiology, Clinical Sciences, Lund University, Sweden (P.G.P.)

    Pyotr G. Platonov https://orcid.org/0000-0002-5592-8717 Department of Cardiology, Clinical Sciences, Lund University, Sweden (P.G.P.)

23. Kristina Hermann Haugaa

    Oslo University Hospital · University of Oslo

    Affiliation as printed

    ProCardio Center for Innovation, Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway and University of Oslo (M. Chivulescu, K.H.H.)

    Kristina H. Haugaa https://orcid.org/0000-0002-4900-0453 ProCardio Center for Innovation, Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway and University of Oslo (M. Chivulescu, K.H.H.)

24. Fırat Duru

    University of Zurich · University Hospital Zurich

    Affiliation as printed

    Department of Cardiology, University Heart Center Zurich, University Hospital Zurich‚ Switzerland (S.C., C.B.B., F.D., A.M.S.)

    Firat Duru https://orcid.org/0000-0002-4748-0158 Department of Cardiology, University Heart Center Zurich, University Hospital Zurich' Switzerland (S.C., C.B.B., F.D., A.M.S.)

25. Anneline S.J.M. te Riele

    Utrecht University · University Medical Center Utrecht

    Affiliation as printed

    Department of Cardiology (L.P.B., A.S.J.M.t.R.), University Medical Center Utrecht, University of Utrecht, The Netherlands

    Anneline S.J.M. te Riele https://orcid.org/0000-0002-4694-4790 Department of Cardiology (L.P.B., A.S.J.M.t.R.), University Medical Center Utrecht, University of Utrecht, The Netherlands

26. Paul Khairy

    Montreal Heart Institute · Université de Montréal

    Affiliation as printed

    Cardiovascular Genetics Center and Electrophysiology Service, Montreal Heart Institute, Université de Montréal, Canada (R.T., L.R., P.K., J.C.-T.)

27. Claudio Tondo

    University of Milan · Centro Cardiologico Monzino

    Affiliation as printed

    Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Department of Clinical Electrophisiology and Cardiac Pacing, Milan, Italy (C.C., C. Tondo)

    Department Biomedical, Surgical and Dental Sciences, University of Milan, Italy (C. Tondo)

    Claudio Tondo https://orcid.org/0000-0002-8500-8313 Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Department of Clinical Electrophisiology and Cardiac Pacing, Milan, Italy (C.C., C. Tondo). Department Biomedical, Surgical and Dental Sciences, University of Milan, Italy (C. Tondo)

28. Hugh G Calkins

    Johns Hopkins University · Johns Hopkins Medicine · Johns Hopkins Hospital

    Affiliation as printed

    Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (A.G., R.T.C., C. Tichnell, B.M., H.T., H.C., C.A.J.)

    Hugh Calkins https://orcid.org/0000-0002-9262-9433 Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (A.G., R.T.C., C. Tichnell, B.M., H.T., H.C., C.A.J.)

29. Cynthia A. James

    Johns Hopkins University · Johns Hopkins Medicine · Johns Hopkins Hospital

    Affiliation as printed

    Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (A.G., R.T.C., C. Tichnell, B.M., H.T., H.C., C.A.J.)

    Cynthia A. James https://orcid.org/0000-0001-8040-4600 Department of Medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, MD (A.G., R.T.C., C. Tichnell, B.M., H.T., H.C., C.A.J.)

30. Ardan Muammer Saguner

    University Hospital Zurich

    Affiliation as printed

    Department of Cardiology, University Heart Center Zurich, University Hospital Zurich‚ Switzerland (S.C., C.B.B., F.D., A.M.S.)

    Ardan M. Saguner https://orcid.org/0000-0003-1896-0803 Department of Cardiology, University Heart Center Zurich, University Hospital Zurich' Switzerland (S.C., C.B.B., F.D., A.M.S.)

31. Julia Cadrin‐Tourigny

    Montreal Heart Institute · Université de Montréal

    Affiliation as printed

    Cardiovascular Genetics Center and Electrophysiology Service, Montreal Heart Institute, Université de Montréal, Canada (R.T., L.R., P.K., J.C.-T.)