ICDs in nonischemic cardiomyopathy

Presented at 10th California Heart Rhythm Symposium, San Francisco, Sep 2019

1. When to consider an ICD in the non-ischemic cardiomyopathy patient without arrhythmia? Sergio L. Pinski, MD, FHRS Cleveland Clinic Florida Weston, FL, USA

2. SCD- HeFT and subsequent meta- analysis Bardy et al. N Engl J Med 2005;352:2251 Desai et al. JAMA 2004;292:2874

3. Declining risk of sudden death in NICM Kober et al. N Engl J Med 2017;377:41

4. The DANISH study Kober et al. N Engl J Med 2016;375:1221

5. Khamis et al. J Clin Epidemiol 2019;113:147

6. Cochrane Meta- Analysis El Moheb et al. Cochrane Database Systematic Reviews 2018

7. EHRA Survey shortly after DANISH Haugaa et al. Europace 2017;19:660

8. Refining the indication-Risk stratification Select patients with higher risk of sudden cardiac death but lower risk of death due to heart failure and competing comorbidities

9. Elming et al. Circulation 2017;136:1772 Older age limits the benefits of ICD

10. Saba et al. Heart Rhythm 2019;16:1065 CRT-P vs CRT-D in elderly pts with NICM

11. Kristensen et al. JACC Heart Fail 2019: (in press ) Risk models in DANISH

12. Goldberger et al. JACC 2014;63:1879 Electrical parameters are mediocre in identifying NICM pts ar risk for sudden death

13. Gulati et al. JAMA 2013;309:896

14. Gulati et al. JAMA 2013;309:896

15. Halliday et al. J Am Coll Cardiol Img 2019;12:1645

16. Becker et al. JACC Cardiovasc Imag 2018;11:1274 Meta- analysis of LGE as predictor of ventricular arrhythmias or LV remodeling in DCM

17. Ongoing randomized trial Cardiac Magnetic Resonance GUIDEd Management of Mild-moderate Left Ventricular Systolic Dysfunction (CMR-GUIDE) ~ 400 pts with ischemic or nonischemic cardiomyopathy, LVEF 36 to 50%, + LGE Randomized to ICD vs ILR End-point is composite of SCD or hemodynamically significant ventricular arrhythmia 2023

18. Di Marco et al. J Am Coll Cardiol HF 2017;5:28 Meta- analysis of LGE as predictor of SD or ventricular arrhythmias in DCM

19. ”Non- ischemic ” cardiomyopathy Acromegaly AL amyloidosis Alcoholic Anthracycline Arrhythmogenic LV Chagas’ disease “Burn out” HCM Cocaine/ metamphetamine Genetic/familial dilated Hemochromatosis Inflammatory/autoimmune PVC-induced LBBB-induced LV non-compaction Muscular dystrophies Pacing-induced Peripartum Post myocarditis Sarcoidosis Tachycardia-induced

20. Kayvanpour et al. Clin Res Cardiol 2017:106:135 Genetic causes of dilated cardiomyopathy

21. Peters et al. Heart Lung Circ 2019;28:31 Correlation between mutated genes and cardiomyopathy phenotype

22. Wahbi et al. Circulation 2019;140:293 Prognostic score for pts with lamin mutations

23. Ortiz- Genga et al. JACC 2016:68:2440 Truncating filamin C (FLCN) mutations carry high risk of sudden cardiac death

24. Gacita & McNally . Circ Heart Fail 2019;12:e005850 Proposed algorithm for high-risk mutations

25. Cleland et al. JACC 2017:70:1028 Reclassification of Risk of Sudden Death

26. My approach to ICD in nonischemic cardiomyopathy Familial DCM with SCD or mutation with high risk of sudden death (LMNA, SCN5A, RBM20, FLCN) Significant LGE in CRM? Treatable condition? Low risk of competing mortality? (younger age, no severe HF (or transplant listed), no comorbidities) Detailed clinical and family history , deep phenotyping (CMR +), genotyping ( ie , MOGE(S) classification , JACC 2014;64:304) ICD ICD No ICD, treat and reevalaute ICD

27. Prabhu et al. J Am Coll Cardiol 2017;70:1949 Prabhu et al. J Am Coll Cardiol EP 2018;4:999 AF ablation and LV fibrosis: The CAMERA-MRI Study

28. Leyva et al. J Am Coll Cardiol 2012;60:1659 Patients with NICM and no fibrosis have excellent long-term prognosis with CRT-P alone

29. Saini et al. JACC Clin Electrophysiol 2016;2:307 CRT responders have lower risk of ventricular arrhythmia

30. Interesting Clinical Dilemma Younger patient with heart block and mild LV dysfunction requiring more or less urgent pacemaker (LMNA, SCN5A, sarcoidosis) Family history? Extracardiac features? Chest CT for sarcoidosis Same day in hospital CMR generally not available Turn around time for genetic test, biopsy too long ? EP study. DF-1 ICD lead for RV pacing with pacemaker- Not MRI compatible

31. Conclusions Current guidelines, based on LVEF, are not specific or sensitive to identify pts who benefit from ICD “ Nonischemic ” cardiomyopathy should not be longer used. Appropriate disease characterization identifies pts with diffent risks, natural history and response to treatment Absence of LGE in CMR identifies pts with much lower risk of sudden death, at any given LVEF Older age decreases the benefit of ICDs RCTs to expand indications are likely. However, large RCTs to restrict indications are not forthcoming. We will have to use clinical judgement.