When CRT May Have A Proarrhythmic Effect?

1. When CRT May Have A Proarrhythmic Effect? Alexandru I Costea, MD Associate Professor of Medicine Director of EP Services at WCMC University of Cincinnati

2. Introduction • CRT improves exercise capacity, quality of life and functional class in patients with severe drug refractory CHF form LV dysfunction and electrical dyssynchrony • Patients with CHF are at risk for SCD due to monomorphic ventricular tachycardia and ventricular fibrillation • It is generally accepted that ICD should be used in addition to CRT therapy in patients with severe CHF due to LV dysfunction • Since the beginning of the CRT there has been a concern that LV stimulation in these patients may be proarrhythmic

3. Introduction • Effective CRT decreases the potential for arrhythmias directly or through positive remodeling: • Reduced sympathetic activity • Increased heart rate variability • Suppresses the frequency of PVC’s • Reduces the ventricular tachycardia events and the need for ICD therapies • Decreases inducibility of sustained ventricular tachycardia during EPS

4. Background • Electrical heterogeneity of myocardium described first in 1991 • Significant differences in the EP properties between the endocardial, epicardial and M cells • M cells prolong the action potential out of proportion to that of epicardium and endocardium in response to slowing of the heart rate or agents that prolong the action potential • The duration of action potential of the M cells determines the QT interval while Epicardial cells determine QT peak interval • Sicouri S, Antzelevitch C. A subpopulation of cells with unique electrophysiological properties: the M Cells. Circ Res 1991;68;1729-41)

5. Background

6. Mechanisms • Trans-mural dispersion of repolarization is defined as the difference between the longest and shortest repolarization times across the LV wall • CRT is based on pacing the LV from the epicardium, reversing the normal endocardial to epicardial activation vector • Abnormal activation sequence accentuates the trans-mural dispersion while amplifying the intrinsic heterogeneity existent at baseline • Medina Ravell V, Kowey P. Effect of Epicardial or Biventricular pacing to prolong QT interval and increase transmural dispersion of repolarization. Circulation 2003:107; 740-746

7. Mechanisms • The non-homogenous depolarization resulted from delayed activation and repolarization of the M cells creates a substrate for reentrant arrhythmias • Reversed activation also prolongs the QT interval and the T peak to T end interval; T peak to T end is a measure of dispersion • This leads to increased EAD induced extrasystole, R on T phenomenon and Torsades de Pointes • Fish JM, Anzelevitch C. Epicardial activation of the left ventricular wall prolongs QT interval and transmural dispersion of repolarization. Circulation 2004:109:2136 -42

8. Mechanisms

9. Mechanisms

10. Mechanisms • QT interval increased from 442.1 ± 6.7 to 464.7 ± 20.5 and T peak to T end increased from 111 ± 15 to 138 ± 24

11. Voltage sensitive dye used experimentally to measure ventricular activation times and conduction patterns • Ischemia was produced gradually during the experiment • Several risk factors for conduction abnormalities leading to VF were identified: • High LV output pacing • Long inter-ventricular delay • LV apical pacing • Haissaguerre M. Optical mapping technique applied to BIV pacing: potential mechanisms for ventricular arrhythmias occurrence. Pacing ClinElectrophysiol 2003; 26: 197 -205 Mechanisms

12. Mechanisms Scar–related VT induction is pacing site specific. Robertson et al. reported that 10% of patients with VT require LV pacing for induction. LV pacing during CRT may facilitate preferential input into the LV reentrant circuit By penetrating the reentry circuit LV pacing could lead to VT Robertson JE, Josephson ME. Anatomic and electrophysiologic correlates of VT requiring ventricular stimulation. Am J Cardiol 1982;48: 263 -268

13. Clinical Evidence • Several cases of monomorphic ventricular tachycardia induced or exacerbated by LV pacing were published starting with 2003 • Groh et al. reported a case of ischemic CMP patient with a preexistent monomorphic VT that had an exacerbation of same VT with LV pacing only • VT was successfully controlled with ATP and Amiodarone Guerra J, Groh W. Increase in VT frequency after biventricular ICD upgrade. J Cardiovasc. Electrophysiol. 14: 1245 -1247; Nov 2003

14. Clinical Evidence • Report of a 75 y old male with ischemic cardiomyopathy • Refractory CHF and LBBB with a QRS of 195 ms • Developed drug resistant monomorphic VT that could be terminated only transiently by ICD therapies • Medical therapy was ineffective • The only effective intervention was inactivation of LV pacing Mykytsey A, Kehoe R. Ventricular Tachycardia Induced by BIV Pacing in Patient with Severe Ischemic Cardiomyopathy. J CardiovascElectrophysiol, Vol 16, 655-658. 6. 2005

15. Clinical Evidence • QT, JT and TDR were measured in 29 patients with CHF during RV, LV and BIV pacing • Both LV and BIV pacing led to prolongation of all three parameters • 4/29 patients developed TDP with LV or BIV pacing • Arrhythmia corrected by RV pacing alone Medina Ravell V, Kowey P. Effect of Epicardial or Biventricular pacing to prolong QT interval and increase transmural dispersion of repolarization. Circulation 2003:107; 740-746

16. Clinical Evidence • First large study group evaluated the incidence of CRT induced arrhythmias on 145 patients • 3.4% patients developed incessant ventricular arrhythmias within 72 hours after implantation: • 4 monomorphic VT in 3 ischemic and 1 non ischemic patients • 1 VF in an ischemic patient • Controlled with antiarrhythmic medication, VT catheter ablation (2 p) and/or discontinuation of LV pacing (permanently in 1 p) Shukla G, Haffajee C. Potential proarrhythmic effect of biventricular pacing: fact or myth? Heart Rhythm 2005; 2: 951-956

17. Clinical Evidence • 191 patients with BIV ICD de novo or as upgradeenrolled. VT/VF incidence, clinical characteristics and management reported • Eight patients (4%) had recurrent sustained monomorphic VT • All patients were men • Seven had ischemic CMP, one had non ischemic CMP Nayal H, Marchlinski F. Ventricular tachycardia storm after initiation of BIV pacing. J CardiovascElectrophysiol, Vol19, 708-715. July 2008

18. Clinical Evidence • All the patients had a history of monomorphic VT prior to the BIV ICD implant (spontaneous or induced during EPS) • No other differences with the rest of the patients • VT occurred at a mean of 16± 12.5 days after BIV pacing was initiated • Medical therapy with amiodarone or lidocaine was ineffective long term although acutely successful Nayal H, Marchlinski F. Ventricular tachycardia storm after initiation of BIV pacing. J Cardiovasc Electrophysiol, Vol19, 708-715. July 2008

19. Clinical Evidence • All the patients had a history of monomorphic VT prior to the BIV ICD implant • VT occurred at a mean of 16± 12.5 days after BIV pacing was initiated Nayal H, Marchlinski F. Ventricular tachycardia storm after initiation of BIV pacing. J Cardiovasc Electrophysiol, Vol19, 708-715. July 2008

20. Clinical Evidence • Four patients agreed to an EP study and had a successful ablation of a reentrant VT • Two patients were managed by turning the LV pacing off • One patient had 2 LV leads in place. Alternate LV pacing corrected the arrhythmias • One patient was managed by decreasing the LV pacing output • Despite management of the VT, all 8 patients developed severe CHF; 3 expired and one received OHT Nayal H, Marchlinski F. Ventricular tachycardia storm after initiation of BIV pacing. J CardiovascElectrophysiol, Vol19, 708-715. July 2008

21. Clinical Evidence RV Pacing: non clinical VT LV Pacing: clinical VT Yamada T, Kay N. Successful catheter ablation of epicardial VT worsened by CRT. Online published ahead publication. Europace. 16 Dec 2009

22. Clinical Evidence Ablation Map and Fluoroscopy VT Entrainment and EGMs

23. Clinical Evidence LV lead entrainment can help diagnosis and localize reentry

24. Clinical Evidence LV lead entrainment can help diagnosis and localize reentry

25. UC Experience • Following 332 patients with BIV ICD implants • LV pacing had to be discontinued in 3 patients: • Symptomatic PVC count affecting % BIV pacing • Worsening CHF in a patient with narrow QRS at baseline • VT salvoes and VF in NICMP – successfully ablated

26. UC Experience

27. UC Experience

28. UC Experience

29. UC Experience

30. UC Experience

31. Patients at Risk • Severe cardiac failure • Prolonged QT at baseline either disease or medication induced • Electrolyte abnormalities • High output LV pacing • Ischemic CMP and location of the LV pacing lead relative to scar • Sustained VT documented prior to BIV implant • ICMP patients usually develop VT, while NICMP usually have VF

32. UC Experience

33. Management Guidelines • Discontinuation of LV Pacing is always effective • Alternate sites of LV pacing can be considered • Minimizing the LV output can be useful • Antiarrhythmics rarely work, but can be used in conjunction with other therapies • VT ablation, usually with epicardial access is necessary

34. Controversies • COMPANION trial demonstrated that BIV pacing has a • beneficial effect on survival; it included both BIV ICD and BIV pacemakers – both groups were compared to a control group but not each other • CARE HF trial showed significant long term benefits of CRT • pacing alone with respect to survival as a single end point • Does CRT ICD provide better survival benefits than CRT P? • Is it safe to implant a CRT P only device without an ICD backup?