Arrhythmia induced Cardiomyopathy by dr vinay.pptx

Arrhythmias induced cardiomyopathy

1. Arrhythmia induced Cardiomyopathies

2. History and Terminology T-CMP : First described by Gossage et al in 1913 in a patient with AF with rapid ventricular response T-CMP: D evelopment of ventricular dysfunction due to rapid ventricular rate irrespective of type of tachycardia P VCs could cause ventricular dysfunction (PVC induced cardiomyopathy) V entricular dysfunction : AF who had a controlled ventricular rate ( AF-induced cardiomyopathy)

3. T erm “ AiCMP ” was introduced Various arrhythmias can result in the development of reversible ventricular dysfunction Mechanism not limited to tachycardia alone

4. definition C ondition in which atrial or ventricular tachyarrhythmias or frequent ventricular ectopy result in left ventricular (LV) dysfunction, leading to systolic HF P artial or complete reversibility once arrhythmia control is achieved

5. Two categories of the condition exist: Arrhythmia-induced : Arrhythmia is the only reason for ventricular dysfunction – Pure Arrhythmia-mediated : Arrhythmia exacerbates ventricular dysfunction and/or worsens HF in a patient with concomitant heart disease - Impure

6. Term Arrythmia induced cardiomyopathy constitutes : Tachycardia induced cardiomyopathy AF induced cardiomyopathy PVC induced cardiomyopathy

7. TACHYCARDIA-INDUCED CM T-CM refers to the presence of a reversible LV dysfunction solely due to increase in ventricular rates, regardless of tachycardia origin Risk of developing T-CM depends not only the type, but also the rate and duration of tachycardia

8. Fenelon et al. proposed Dilatation of the heart or heart failure and Chronic or very frequent cardiac arrhythmia (incessant supraventricular tachycardia, AF, or flutter, incessant ventricular tachycardia) Chronic tachycardia that occurs > 10–15% of the day may result in cardiomyopathy No precise ventricular rate s/o causation, however rates > 100/min predispose to AIC Atrial rate is >150% of that predicted for age, cardiomyopathy develops Fenelon et al; Pacing Clin Electrophysiol 1996;19:95–106

9. Incidence ADULTS In one study 2.7 % of all the patients referred for RFA Atrial Tachycardia : 8.3 - 10% of patients Frequent VPCs and NSVT runs :9 - 34% PJRT : 20% - 50% ( highest association with T-CM)

10. PEDIATRIC POPULATION In children T-CM is caused by AT (59%) Permanent junctional reciprocating tachycardia (23%) Ventricular tachycardia (7%) A trial ectopic tachycardia (AET) : 28% had AIC (pediatric multicenter study)

11. causes AF and atrial flutter with rapid ventricular response( most common ) I ncessant or very frequent paroxysmal AT Persistent atrioventricular (AV) reciprocating tachycardia AV nodal re-entrant tachycardia S ustained sinus tachycardia F requent ventricular tachycardias (idiopathic, bundle branch, and fascicular) P acemaker-mediated tachycardia

12. pathophysiology In animal models : P ersistent tachycardia using a continuous rapid atrial or ventricular pacing develop HF symptoms LV systolic dysfunction and dilatation, D ecrease in LV dP / dtmax and myocardial blood flow I ncrease in LV wall stress , end-diastolic pressure and volume

13. T ime-dependent and highly predictable manner

14. Cessation of tachy-pacing results in Normalization of right atrial and arterial pressure with significant recovery of LVEF and cardiac output by 48 h Full normalization after 1 to 2 weeks After 1 week LV mass increases by 26% LV remains dilated M yocytes continue to demonstrate contractile dysfunction Ca cycling (sum of Ca uptake and Ca release), Ca-uptake, and CK activity significantly normalized at 4 weeks

15. Clinical features V ariable time from onset of arrhythmia symptoms to development of T-CM 3 to 120 days M ore severe LV dysfunction (LVEF 29.3± 6.6%) in T-CM when compared with dilated and inflammatory CM (32.1 ±10.2% and 41.9 ± 12.9%, respectively; p < 0.001)

16. symptoms P alpitations (29%) HF class III to IV (47%) S yncope/presyncope (12%) As ymptomatic Higher the rates earlier the HF occurrence and symptoms (A Flutter with 2:1 AV block) Sudden cardiac death : 8% to 12%

17. The relationship of arrhythmia to cardiomyopathy can be difficult to determine because an arrhythmia could exist for years before its recognition and before cardiomyopathy develops Which came first - Chicken or Egg question

18. When to suspect ? P atients with LV dysfunction and a prior or persistent or frequent paroxysmal tachycardia without obvious etiology S uperimposed T-CM should be considered despite underlying secondary CM (ischemic, infiltrative, or toxic/drug-related) if the tachycardia is present

19. How To Differentiate From Dilated Cardiomyopathy? LVEF ≤ 45% and LVEDD ≤ 61 mm was predictive of TIC with a sensitivity of 100% and a specificity of 71% LVEF < 30% and LVEDD ≤ 66 mm was predictive of TIC with a sensitivity of 100% and a specificity of 83% LV size on admission was smaller for TIC patients (LV EDD 57.6+7.2 mm, LV ESD 49.4+8.0 mm) than in the DCMP group (LV EDD 63.4+8.8 mm, LV ESD 55.3+9.6 mm, P < 0.05) TIC patients had better prognosis (cardiac death , heart failure hospitalization ) during follow-up Jeong et al. Clin Cardiol 2008;314:172-178

20. How To Differentiate From Dilated Cardiomyopathy? Endomyocardial biopsy can be useful Less fibrosis Less T cells and microphages Enhanced myocyte size Mueller AL, et al. J Am Coll Cardiol 2017;69:2160-2172

21. Echocardiography and mri Echocardiogram or C-MRI can assist in excluding other etiologies T-CM is characterized by a dilated CM (increased LV end-diastolic dimension and area) with moderate to severe biventricular systolic dysfunction and normal LV septal and posterior wall thickness (lack of hypertrophy) Mitral insufficiency may be present due to LV and mitral annular dilatation with lack of leaflet coaptation

22. Neurohormonal markers BNP and pro-BNP are commonly elevated depending on the degree of heart failure and CM S udden drop of pro-BNP within a week of elimination of tachycardia is supportive of T-CM Final diagnosis of T –CM be only confirmed after recovery or improvement of LV systolic function within 1 to 6 months after elimination of the tachyarrhythmia

23. Prognosis Recovery of LV functions is extremely variable May be complete, partial or none Greatest improvement occurs in 1 st month and may take upto 6 to 12 months (usually 4 to 12 weeks) Recovery is greatest in patients having more profound depression at presentation Cardiac MRI may help in predicting the reversibility of LV dysfunction after achieving sinus rhythm The absence of ventricular scar or scar burden < 10 % predicted reversibility Watanabe cardiomyopathy. Int Heart J 2008;49:39–47 Gupta et al; Int J Cardiol 2014;172:40–6

24. Treatment Initial treatment in form of treatment of heart failure with beta blockers, ACEI/ARBs/ARNI, MRA and diuretics Because there is reversibility once tachycardia is eliminated heart rate control by rate control or rhythm control forms the cornerstone of the therapy Results in reduction in EDV and ESV and improvement in EF, symptoms Elimination of tachycardia resolves LV function within 4 to 12 weeks and heart failure symptoms by atleast 1 class

25. Recovery is not always complete Histopathological abnormalities, diastolic dysfunction, and ventricular dilatation with a hypertrophic response may persist despite normalization of LVEF If it is arrhythmia mediated rather than induced, the reversibility is only partial, but control of arrhythmia should be done to accrue those small benefits

26. Recurrence With the recurrence of arrhythmia the symptoms will return faster and almost or more than the previous severity Persistence of underlying histopathological abnormalities from initial presentation is the likely reason However complete recovery can still be possible with eliminating tachycardia Permanent treatment such as ablation therapy should be especially considered in arrhythmias with a high success or cure rate such as atrial flutter, AV nodal re-entrant tachycardia, AV reciprocating tachycardia, and AT Ling LH et al; Circ Arrhythm Electrophysiol 2013;6:697–704

27. Follow up Should be monitored every 6 monthly with Holter monitoring every year In some patients even though LV function becomes normal their chamber sizes are enlarged

28. AF induced cardiomyopathy Defined as LV dysfunction in paroxysmal or persistent AF despite appropriate rate control Limited evidence – Duration and irregularity rather than tachycardia rate predicts occurrence of CM So our previous understanding “Rate control” non inferior to “rhythm control” in AF with CM is in doubt In all, 25 – 50% of patients with LV dysfunction and AF, demonstrate some degree of TIC *Redfield et al; Mayo Clin Proc 2000;75:790–5

29. Dissecting whether the LV impairment is due to underlying structural heart disease or the lack of atrial transport and rapid, irregular ventricular rates in their own right is difficult Resting heart rate are a poor indicators of rate control in patients of chronic AF, minimal activity can induce tachycardia leading to T-CM

30. Mechanism Not known Probable Irregularity with calcium mishandling Loss of atrial contraction a/w sympathetic activation contributing to Limited ventricular filling Increased filling pressures Functional mitral regurgitation Diastolic dysfunction

31. When to suspect ?? D iagnosis of exclusion Should be primarily suspected in patients with nonischemic CM and persistent AF that do not improve after appropriate medical therapy and rate control A final AF-CM diagnosis can only be made if LV systolic function improves or normalizes after elimination of AF

32. Treatment Restoration of sinus rhythm should be considered if AF-CM is suspected AF ablation has been reported to achieve sinus rhythm from 50% to 88% in both paroxysmal and persistent AF patients with HF and CM AADs have an overall 30% to 50% success rate to maintain sinus rhythm with frequent discontinuation due to side effects

33. CASTLE AF Catheter ablation versus medical therapy (rate or rhythm control) in AF patients with HF (EF < 35%) In the ablation group, 63% of patients were in sinus rhythm at 60 months versus 22% in the medical-therapy group The composite primary end point — death or hospitalization for worsening heart failure —occurred in significantly fewer patients in the ablation group than in the medical-therapy group ( 51 patients [28.5%] vs. 82 patients [44.6%]; P = 0.006 Suggests that maintenance of sinus rhythm is beneficial when achieved without the use of antiarrhythmic drugs Nassir F. Marrouche et al; N Engl J Med 2018;378:417-27

34. CAMERA‐MRI trial Optimal rate control versus catheter ablation to restore sinus rhythm 97% on beta blockade and 94% on renin angiotensin aldosterone system inhibition The primary endpoint - absolute EF improvement of 18.3% in the catheter ablation arm compared to 4.4% in the medical rate control arm (P < 0.0001) Absence of LGE on MRI portended better outcomes with an absolute improvement in LVEF of 22% in LGE negative compared with 11% in LGE positive group (P = 0.0069) Catheter ablation arm improvements in NYHA class and reduction in BNP Prbhu et al; J Am Coll Cardiol . 2017;70:1949–61.

35. AATAC trial Patients with HF and persistent AF, catheter ablation is superior to amiodarone in achieving freedom from AF at 2 years follow-up Randomized 203 patients Freedom of AF (70% vs. 34%) Q uality of life HF admissions (31% vs. 57%) M ortality (8% vs. 18%) LVEF improved 9.6%±7.4% in the ablation arm versus 4.2%±6.2% in the amiodarone arm ( P<0.01 ) DI Biase et al; AATAC Multicenter Randomized Trial. Circulation 2016;133:1637–44

36. CABANA TRIAL In this randomized clinical trial involving 2204 patients with AF, catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest (8.0% vs 9.2%, respectively; hazard ratio, 0.86) 5.2% vs 6.1% for all-cause mortality (HR, 0.85 ) 51.7% vs 58.1% for death or cardiovascular hospitalization (HR, 0.83 [95% CI, 0.74-0.93];  P  = .001) Ablation was not done in especially in HF with AF patients, all the patients were included

37. Systematic review of 19 studies (914 patients) evaluating AF ablation in patients with concomitant LV dysfunction LVEF increased by 13.3% (95% CI 11% to 16%) 57% maintained sinus rhythm, after a single procedure and 82% after >1 procedure and/or use of anti-arrhythmic drugs Ganesan et al Heart Lung Circ.  2015 Mar;24(3):270-80

38. PVC-CM PVC-CM is defined as the development of LV dysfunction caused solely by frequent PVCs. Superimposed PVC-CM can be defined as worsening of LVEF by at least 10% due to frequent PVCs in a previously known CM PVC burden > 10% is considered high and enough to cause PVC-CM Penela et al suggested PVC burden of ≥13% as the ideal cut off to predict LV dysfunction with a sensitivity of 100% and a specificity of 85%

39. Incidence PVCs are seen in 1 to 4 % of patients without heart disease recorded in routine 10 second ECG 40 to 50 % patients in 24 to 48 hour ambulatory ECG monitoring Increases with age 70% with subjects 75 years or older Incidence of PVC-CM is 7 % with high PVC burden (>10%) 9 to 30 % among patients referred for ablation

40. ACUTE EFFECTS OF PVCs AND POTENTIAL TRIGGERS OF PVC-CM Heart rate irregularity Postextrasystolic potentiation LV dyssynchrony AV dyssynchrony I ncreased heart rate U nclear if and how these triggers contribute to the development of PVC-CM

41. H eart rate irregularity and post- extrasystolic potentiation play a limited role Gerstenfeld’s group : LV dysfunction is more in PVCs from LV epicardium (higher degree of dyssynchrony ) compared with endocardial RV free wall Epicardial PVCs and QRS >150 ms were predictors of PVC-CM

42. Mechanism of pvc-cmp C ellular mechanism has not been extensively studied The primary cause of contractile dysfunction in PVC-CM appears to be disorders of the calcium induced calcium release mechanism itself, with alterations of L-type Ca channel and Ryanodine receptor function proposed as a potential mechanism Histopathological abnormalities are distinct without evidence of increased inflammation or apoptosis and minimal or no fibrosis Differs from other causes of tachy induced CM by less inflammation or apoptosis and minimal or no fibrosis and less enhancement on Cardiac MR

43. Predictors of PVC- CM Male sex Higher PVC burden Major predictor At least 10% PVC burdon is required to induce PVC-CM Variable coupling interval QRS duration > 150 ms Epicardial origin

44. Lack of symptoms Duration of palpitations >30 months Genetic predisposition( R222Q missense variant of the Nav1.5 subunit of sodium channel) L ess frequently reported independent predictors are Body mass index >30 kg/m2 L ess variability in circadian PVC distribution P resence of retrograde P-wave AV dyssynchrony during PVCs

45. Clinical features and diagnosis May present in weeks to years after onset of PVC’s Diagnosis of exclusion Burden > 10 % 24 hour Holter identifies only 53% of the patients Ideally a 6 day ambulatory ECG is required for diagnosis(Loring et al)

46. Treatment PVC suppression by either RFA or anti anti arrhythmic drugs 2 to 12 weeks before onset of improvement PVC suppression is considered successful if burden is decreased by 80% of baseline PVCs Amiodarone trial can be given for a 3 to 6 months to assess improvement in LV function and then proceed for ablation

47. Radiofrequency ablation vs aad No randomized trials comparing both the strategies Both have similar long-term PVC suppression success rate between 70% and 80% C omplication rates of RFA have been reported between 5% to 8% A ntiarrhythmics have a discontinuation rate of near 10%

48. PVC reduction was greater with RFA than antiarrhythmics (mean reduction: RFA 15.5 ± 1.3% vs. AADs 4.8 ± 0.8; p < 0.001) RFA may be more effective in patients with lower PVC burdens(single retrospective study )

49. PVC suppression in PVC-CM has been shown to improve LV function LV dilatation mitral regurgitation BNP levels The mean improvement of LVEF after RFA in most studies is between 10% and 15%

50. Independent predictors of response to RFA Successful ablation myocardial scar mass <9 g reduction of mean PVC burden

51. Which came first Young healthy patients with no underlying cardiac disease Absence of known coronary artery disease Frequent PVCs (often > 20,000 beats/day) One or two primary morphologies, suggesting that one or two localized regions of abnormal myocardium are generating the PVCs rather than widespread myocardial disease that can be expected to give rise to multiple morphologies of PVCs Right ventricular outflow tract, LV outflow tract, or fascicular PVC QRS morphology Possibly preserved myocardial thickness and absence of scar on echocardiography Mishi Bhushan , Samuel J. Asirvatham , MD Current Heart Failure Reports 2009, 6:7–13

52. PVC in asymptomatic patients If the burden of PVCs is > 10% in asymptomatic patients (without LV dysfunction), these patients require close monitoring for the development of HF or LV dysfunction Because ablation carry a risk of <1% tamponade and even mortality even if an asymptomatic patient carries huge burden of VPCs needs to be monitored for development of LV dysfunction

53. Current data show improvement in LV function and symptoms with PVC control No evidence suggesting decreased risk of mortality

54. Conclusion Tachycardia-induced cardiomyopathy is a known complication of AF/flutter. The definition of AIC is one of exclusion. Cardiac MRI and occasionally myocardial biopsy can be used to help differentiate it from other cardiomyopathies and to prognosticate about reversibility The presence of TIC is a strong indication for interventional therapy in patients who have failed medical management since elimination causes improvement in LV function Catheter ablation, an effective tool is available which can restore sinus rhythm without the detrimental effects of drug toxicity

55. thanks