PVCs: Do they cause Cardiomyopathy? Raed Abu Sham a, M.D.

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1 PVCs: Do they cause Cardiomyopathy? Raed Abu Sham a, M.D. Cardiologist and Electrophysiologist

2 No conflict of interest related to this presentation

3 Objectives 1. PVCs are benign. What is the Evidence? 2. Effects of PVCs on Mechanical Function of the Heart 3. Hemodynamic effects of PVCs 4. Risk of LV dysfunction from frequent PVCs 5. Is it reversible or non-reversible CMP? 6. PVCs in ischemic and non-ischemic CMP 7. What the guidelines tell us to do?

4 Case presentation Mrs. L.J is a 56 YOFP with DM and HTN. C/O atypical chest pain and fatigue. There was no dyspnea, palpitations or syncope. Coronary Angiogram: normal in Echocardiogram: 2013: LVEF 60% 2014: LVEF 55% 2015: LVEF 30% She was referred for ICD implant

5 ECG in the clinic

6 24-hours Holter

7 What the next step should be? A. Proceed for ICD implantation B. Wait for 9 months on medical therapy C. Start Amiodarone D. Referral for EP Study

8 Objectives PVCs are benign. What is the Evidence? Effects of PVCs on Mechanical Function of the Heart Hemodynamic effects of PVCs Risk of LV dysfunction from frequent PVCs Is it reversible or non-reversible CMP? PVCs in ischemic and non-ischemic CMP What the guidelines tell us to do?

9 The first recorded description of PVCs It was described as intermittent perturbations interrupting the regular pulse. It was from the early Chinese physician Pien Ts Io, around 600 BC. He was the master in pulse palpation and diagnosis.

10 Pien Ts Io years BC He noted that: these irregularities did not interfere with normal lifespan when they were occasional but an ominous prognosis was implied if they were frequent.

11 Idiopathic PVCs are usually associated with a benign course from the standpoint of arrhythmic death. What is the Evidence?

12 71 subjects with frequent PVCs, [13.4%] Followed for yrs, [mean 6.5 yrs] 2 death: 1 SCD, 1 cancer

13 the long-term prognosis in asymptomatic healthy subjects with frequent and complex ventricular ectopy is similar to that of the healthy U.S. population and suggests no increased risk of death.

14 61 pts who having frequent RV PVCs contacted after 15 ± 2 years (12 to 20) The primary end point was to ascertain the presence of cases of sudden death and development of ARVD. At the end of the follow-up, 55 pts were alive six died, none of sudden death 47 pts had normal ECG In 24 patients (51%) extrasystoles were no longer present at Holter monitoring

15 1. No patient died of sudden death 2. No patient developed ARVC 3. Two-thirds of the patients were asymptomatic 4. in half of the patients, ectopy disappeared

16 Objectives PVCs are benign. What is the Evidence? Effects of PVCs on Mechanical Function of the Heart Hemodynamic effects of PVCs Risk of LV dysfunction from frequent PVCs Is it reversible or non-reversible CMP? PVCs in ischemic and non-ischemic CMP What the guidelines tell us to do?

17 2-D echo was used to quantitate LV function during and immediately after single PVC in dogs.

18 12 successive beats during NSR UCHIYAMA, Am J Cardiol 1981

19 PVC with Long Coupling Interval CI = 600 ms UCHIYAMA, Am J Cardiol 1981

20 PVC with Short Coupling Interval CI = 400 ms UCHIYAMA, Am J Cardiol 1981

21 Objectives PVCs are benign. What is the Evidence? Effects of PVCs on Mechanical Function of the Heart Hemodynamic effects of PVCs Risk of LV dysfunction from frequent PVCs Is it reversible or non-reversible CMP? PVCs in ischemic and non-ischemic CMP What the guidelines tell us to do?

22 PVC with Long Coupling Interval 11% UCHIYAMA, Am J Cardiol 1981

23 PVC with Short Coupling Interval 57% UCHIYAMA, Am J Cardiol 1981

24 PVC with Short Coupling Interval Relative Bradycardia

25 Objectives PVCs are benign. What is the Evidence? Effects of PVCs on Mechanical Function of the Heart Hemodynamic effects of PVCs Risk of LV dysfunction from frequent PVCs Is it reversible or non-reversible CMP? PVCs in ischemic and non-ischemic CMP What the guidelines tell us to do?

26 239 pts with frequent, RVOT or LVOT PVCs (>1000 beats/ day). No heart disease by echo and MRI. Follow up for 5.6 ± 1.7 years No patients exhibited any serious cardiac events.

27 Change in the LVEF and LVDd over the time course with a different PVC prevalence

28 Time course of changes in LVEF and LVDd in 13 pts developed LV dysfunction

29 Is normal Ejection Fraction means normal heart?

30

31 13 dogs were implanted PMs to pace in bigeminy for 12 wks. The PVC group developed CMP LVEF 40±5% versus 61±4%; P= PVC-induced CMP resolved within 2 to 4 weeks after discontinuation of PVCs.

32 LV Dysfunction Induced by Frequent PVCs No inflammation, fibrosis, or changes in apoptosis and mitochondrial oxidative phosphorylation were observed Huizar F et al. Circ Arrhythm Electrophysiol. 2011;4:

33 PVC myocytes had prolonged APDs with exaggerated beat-to-beat variations Wang Y. et al. Heart Rhythm 2014; 11:

34 Objectives PVCs are benign. What is the Evidence? Effects of PVCs on Mechanical Function of the Heart Hemodynamic effects of PVCs Risk of LV dysfunction from frequent PVCs Is it reversible or non-reversible CMP? PVCs in ischemic and non-ischemic CMP What the guidelines tell us to do?

35 1998 vol. 73 no pts with more than 20,000 PVCs/24 h LVEF 40% Started on Antiarrhythmics

36 After 3 to 6 months... Five patients had a reduction ( 75%) in PVCs. Four patients had significant improvement in clinical functional status and the LVEF: From 27 ± 10% to 49 ± 17%, (P = 0.04)

37 26 year old woman baseline after (6m) VPCs 25-56K ~1600 LVd 65/48 57/39 LVEF 43% 58%

38

39

40 LVEF before and after catheter ablation Successful ablation Control Bogun F, Heart Rhythm 2007;4:

41 Objectives PVCs are benign. What is the Evidence? Effects of PVCs on Mechanical Function of the Heart Hemodynamic effects of PVCs Risk of LV dysfunction from frequent PVCs Is it reversible or non-reversible CMP? PVCs in ischemic and non-ischemic CMP What the guidelines tell us to do?

42

43

44 Assessment of LV Function LVEF LVEF

45 30 patients (mean age 59±12) Mean EF 38%±15% structurally abnormal hearts based on: scar on CMR, or history of CMP before the presence of frequent PVCs. Heart Rhythm 2015;12:

46 c c

47 When Do We Ablate? Frequent PVCs > 10,000/24 hours Symptomatic LV dysfunction Monomorphic Accessible Associated VT

48 Objectives PVCs are benign. What is the Evidence? Effects of PVCs on Mechanical Function of the Heart Hemodynamic effects of PVCs Risk of LV dysfunction from frequent PVCs Is it reversible or non-reversible CMP? PVCs in ischemic and non-ischemic CMP What the guidelines tell us to do?

49

50

51

52 Back to our patient Mrs. L.J is a 56 YOFP with DM and HTN. C/O atypical chest pain and fatigue. There was no dyspnea, palpitations or syncope. Coronary Angiogram: normal in Echocardiogram: 2013: LVEF 60% 2014: LVEF 55% 2015: LVEF 30% She was referred for ICD implant Successful ablation was done on October 13, 2015 in the RVOT. Echo was done before discharge and showed LVEF 40%! 24-hour Holter was done and showed <1% PVCs (non-ot) Three months Echo is pending.

53 Take home message 1. Persistent bigeminy halves pulse rate. 2. High burden PVC associated with reversible form of LV dysfunction. 3. Radiofrequency Catheter Ablation is effective therapy for PVC-induced CMP.

54

55 Characteristics of Patients who may Develop CMP 1. If PVCs are frequent ( 10/min), ( 24%) 2. Long duration [older patients] 3. Lack of palpitations 4. Have a short coupling interval 5. Coupling Interval Dispersion 6. Epicardial origin 7. Increased BMI 8. The presence of a retrograde P-wave following a PVC In press: Heart Rhythm 2015; 0:0 8 Kawamura M et al. J Cardiovasc Electrophysiol Jul;25(7): Ban J et al. Europace (2013) 15,

56 Predictors of reversibility of LV systolic dysfunction in patients with PICMP 1. Longer PVC duration 2. Absence of myocardial scar 3. Effective elimination of PVCs (>80% reduction in PVC burden) 4. Early improvement in LVEF at 1-week Del Carpio Munoz F et al. J Cardiovasc Electrophysiol 2011; 22: Yokokawa M et al. Heart Rhythm 2012; 9: Deyell MW et al. Heart Rhythm 2012; : Hasdemir C et al. Pacing Clin Electrophysiol 2012; 35:

57 PVCs + depressed LV function:

58 Patient Characteristics Comorbidity PVCs Resulting from Cardiomyopathy Older patients with CAD HTN, IHD, Myocarditis, Family Hx of Structural HD PVCs-Induced CMP Healthy Individuals Often no prior history or family history Frequency of PVCs < 5000/24 hr > 10,000/24 hrs Pattern of PVCs Polymorphic Monomorphic QRS Morphology Non-specific RVOT, LVOT morphology Response to AA Therapy Response to RFA No improvement in LV function Required to reduce the ICD shocks If PVCs suppressed, LV function improves Curative

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