PVC induced Cardiomyopathy

Raja Selvaraj, JIPMER

Introduction

Tachycardia induced Cardiomyopathy?

Heart failure
Systolic dysfunction
Due to prolonged elevated heart rate (> 100)
Reversible on control of arrhythmia

TIC is more common and better understood entity

PVC induced cardiomyopathy

First reported in a small series in 1998
Less well understood
"Tachycardia" / Repetitive dyssynchronous activation / irregularity of rhythm

Less well understood is LV dysfunction due to PVCs Duffy in small series found improvement in lvef after pharmacologic suppression of pvcs short cycles may contribute, dyssychrony also may, maybe irregularity of rhythm may play a role

Duffee DF, Shen WK, Smith HC. Suppression of frequent premature ventricular contractions and improvement of left ventricular function in patients with presumed idiopathic dilated cardiomyopathy. Mayo Clinic Proc 1998;73:430–3. 10.1016/S0025-6196(11)63724-5

Canine models

Huizar JF.. Ellenbogen KA, Wood MA. Left ventricular systolic dysfunction induced by ventricular ectopy: a novel model for premature ventricular contraction-induced cardiomyopathy. Circ Arrhythm Electrophysiol 2011;4:543–549.

But it seems a true entity. In a canine model, reproducibly produced LV dysfunction

Patient with PVCs - Clinical scenarios

Symptomatic PVC - treat to reduce symptoms
Asymptomatic PVC, normal LV
PVCs, LV dysfunction, no heart disease
PVCs, LV dysfunction and heart disease

Different clinical scenarios in which patients with PVCs present symptoms - easy, need to be treated lv dysfunction, no heart disease - good chance of recovery lv dysfunction and heart disease - may partly improve normal lv and no symptoms - dilemma

PVCs, LV dysfunction and no other heart disease

Causation and recovery

Cardiomyopathy with PVC or PVC with cardiomyopathy ?
Around 80% recover
Markers for recovery
- No heart disease on evaluation
- High PVC burden
- Morphology consistent with idiopathic PVCs

No hard markers to predict recovery Generally idiopathic pvcs and high burden should suggest causation

Dont miss treatable heart disease

Coronary artery disease
Sarcoidosis
Tuberculosis
CAG / Cardiac MRI

CAD and ischemia - typically arrhythmia is polymorphic VT, but can present as PVCs

Higher PVC burden in those with LV dysfunction

Related to burden / frequency
Frequency - 16 (1) to 24 % (2)
Burden - 10000 (3)

Hasdemir C et al. Tachycardia-induced cardiomyopathy in patients with idiopathic ventricular arrhythmias: the incidence, clinical and electrophysiologic characteristics, and the predictors. J Cardiovasc Electrophysiol. 2011 Jun;22(6):663-8.

Baman TS, .. Oral H, Morady F,Bogun F. Relationship between burden of premature ventricular complexes and left ventricular function. Heart Rhythm. 2010 Jul;7(7):865-9.

Kanei et al. Frequent premature ventricular complexes originating from the right ventricular outflow tract are associated with left ventricular dysfunction. Ann Noninvasive Electrocardiol. 2008 Jan;13(1):81-5.

PVC burden

Baman et al. Relationship between burden of premature ventricular complexes and left ventricular function. Heart Rhythm. 2010 Jul;7(7):865-9.

PVC duration as marker of recovery ?

In patients with frequent PVCs and successful ablation, QRS duration was associated with recovery of LV function (1)
Very long QRS may indicate permanent scarring
Cut off of 150 ms suggested by others (2, 3)

Deyell MW .. Marchlinsky. Predictors of recovery of left ventricular dysfunction after ablation of frequent ventricular premature depolarizations. Heart Rhythm 2012;9:1465–72.

Yokokawa M, Kim HM, Good E, et al. Impact of QRS duration of frequent premature ventricular complexes on the development of cardiomyopathy. Heart Rhythm 2012;9:1460–4.

Del Carpio Munoz F, Syed FF, Noheria A, et al. Characteristics of premature ventricular complexes as correlates of reduced left ventricular systolic function: study of the burden, duration, coupling interval, morphology and site of origin of PVCs. J Cardiovasc Electrophysiol 2011;22:791–8.

Marchlinsky's group - reversible LV function in 24 of 37 wider qrs associated with less recovery confirmed in other studies

QRS duration and reversibility of LV dysfunction

Deyell MW .. Marchlinsky. Predictors of recovery of left ventricular dysfunction after ablation of frequent ventricular premature depolarizations. Heart Rhythm 2012;9:1465–72. DOI: 10.1016/j.hrthm.2012.05.019; PMID: 22640894

Role of medical management

Ablation superior to Metoprolol or Propafenone (1)
Flecainide may be a good option (2)
Amiodarone effective in heart failure and improves EF (3)

Ling Z et al. Radiofrequency ablation versus antiarrhythmic medication for treatment of ventricular premature beats from the right ventricular outflow tract: prospective randomized study. Circ Arrhythm Electrophysiol 2014;7:237–3.

Capucci et al. A double-blind crossover comparison of flecainide and slow-release mexiletine in the treatment of stable premature ventricular complexes. Int J Clin Pharmacol Res. 1991;11:23–33
Singh SN, Fletcher RD, Fisher SG, Singh BN, Lewis HD, Deedwania PC, Massie BM, Colling C, Lazzeri D. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. N Engl J Med. 1995;333:77–82.

Flecainide in normal hearts amiodarone in lv dysfunction But overall, ablation is a better choice

PVCs, LV dysfunction and other heart disease

Heart disease / LV dysfunction / frequent PVCs

PVCs may contribute to LV dysfunction
Higher PVC burden may suggest significant contribution
Treatment may result in partial improvement of LV dysfunction

Non ischemic Cardiomyopathy

LV dysfunction preesxistent in 20, diagnosed simultaneously in 49
Improvement also seen in those with preexisting cardiomyopathy
More modest improvement in these patients
less response when initial EF was lower

Mountantonakis SE, Frankel DS, Gerstenfeld EP, et al. Reversal of outflow tract ventricular premature depolarization–induced cardiomyopathy with ablation: effect of residual arrhythmia burden and preexisting cardiomyopathy on outcome. Heart Rhythm 2011;8:1608–14. DOI: 10.1016/j.hrthm.2011.04.026; PMID: 21699837

In patients undergoing pvc ablation, those with dcmp diagnosed before had less improvement but they still had some improvement

Ischemic Cardiomyopathy

Sarrazin .. , Morady F, Bogun F. Impact of radiofrequency ablation of frequent post-infarction premature ventricular complexes on left ventricular ejection fraction. Heart Rhythm . 2009;6:1543–1549.

Patients with previous MI also can have improvement in ef if frequent pvcs are treated

Important consideration in patients eligible for ICD / CRT

LV dysfunction, eligible for device implant, with frequent PVCs
Consider ablation before CRT or ICD
Indication removed in 64% after successful ablation (1)
Wait 3-12 months for potential recovery

Ablation of frequent PVC in patients meeting criteria for primary prevention ICD implant: Safety of withholding the implant. Heart Rhythm 2015;12:2434–2442

Reversal of ICD indication after ablation

Penela D, .. M, Brugada J, Mont L, Berruezo A. Ablation of frequent PVC in patients meeting criteria for primary prevention ICD implant: Safety of withholding the implant. Heart Rhythm. 2015 Dec;12(12):2434-42.

Sustained successful ablation in those with >13% PVCs removed ICD indication

PVCs with normal LV function and no symptoms

PVCs are not uncommon

40 to 75% in 24 to 48 hour Holter recordings (1)
Only a fraction of them are at risk
General cardiologists tend to under treat
Electrophysiologists seem to over treat

Ng GA. Treating patients with ventricular ectopic beats.Heart. 2006;92:1707–1712.
David Callans. Premature Ventricular Contraction-induced Cardiomyopathy. Arrhythmia & Electrophysiology Review 2017; 6(4):153–5

PVC burden and risk

Higher burden seen in those presenting with cardiomyopathy
Does not directly translate to risk of future development of LV dysfunction

Burden is not only factor

Very variable relationship
Small, early series of 8 patients with LV dysfunction and PVCs (7 improved after successful ablation) (1)
Mean ct > 17k pvcs, but 2/8 has < 6k pvcs

Yarlagadda et al. Reversal of cardiomyopathy in patients with repetitive monomorphic ventricular ectopy originating from the right ventricular outflow tract. Circulation 2005;112:1092–7. DOI: 10.1161/CIRCULATIONAHA.105.546432; PMID: 16103234

PVCs and LV dysfunction - factors other than PVC burden

Site of origin - RV PVCs more prone to produce LV dysfunction compared to LV PVCs ?
PVC QRS duration > 140 ms / 150 ms (1, 2)
PVC coupling interval < 600 ms (3)
Interpolation (4)

Del Carpio Munoz .. Asirvatham SJ. Characteristics of premature ventricular complexes as correlates of reduced left ventricular systolic function: study of the burden, duration, coupling interval, morphology and site of origin of PVCs. J Cardiovasc Electrophysiol. 2011 Jul;22(7):791-8.

Yokokawa M .. , Morady F, Bogun F. Impact of QRS duration of frequent premature ventricular complexes on the development of cardiomyopathy. Heart Rhythm. 2012 Sep;9(9):1460-4.

Sun Y et al. The influence of premature ventricular contractions on left ventricular function in asymptomatic children without structural heart disease: an echocardiographic evaluation. Int J Cardiovasc Imaging. 2003 Aug;19(4):295-9.

Olgun H, Yokokawa M, Baman T, et al. The role of interpolation in PVC-induced cardiomyopathy. Heart Rhythm 2011;8:1046–9.

All relationships have been inconsistent, burden still remains only clinically used marker of risk

Burden as denoted by number of freq of PVCs have correlated with incidence of LV dysfunction Varying cut-offs have been proposed, but obviously, there is no magic number other important factors might be PVC QRS duration, PVC coupling interval and interpolation

What is actual rate of development of cardiomyopathy ?

Only one prospective study
249 patients with > 1000 PVCs / 24 h, mean FU > 5 yrs
13 patients developed fall in EF > 6%

Niwano S et al. Prognostic significance of frequent premature ventricular contractions originating from the ventricular outflow tract in patients with normal left ventricular function. Heart 2009;95:1230–7. DOI: 10.1136/hrt.2008.159558; PMID: 19429571

Prospective follow up for 4 years

Niwano S et al. Prognostic significance of frequent premature ventricular contractions originating from the ventricular outflow tract in patients with normal left ventricular function. Heart 2009;95:1230–7. DOI: 10.1136/hrt.2008.159558; PMID: 19429571

An argument for a conservative approach

No good markers to identify those at risk of developing LV dysfunction
Patients prone to develop LV dysfunction often present with same
Those presenting with normal LV function only infrequently develop LV dysfunction
Conservative management may suffice for most
Guidelines recommend conservative management and follow up imaging

PVC burden not sensitive or specific enough Other markers have no consistent relation Only small percentage develope lv dysfunction finally

ACC guidelines

Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Heart Rhythm 2017; DOI: 10.1016/j.hrthm.2017.10.036;

Summary

Symptomatic patients need treatment
Large number of PVCs in presence of LV dysfunction - trial of therapy warranted
PVCs may contribute to / worsen LV dysfunction in underlying heart disease and trial of therapy is warranted
Ablation often is preferable to medical management in these patients
Treatment of frequent PVCs in absence of symptoms or LV dysfunction - decision in discussion with patient, observation suffices for most
Follow up is the preferred option for these patients

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PVC induced Cardiomyopathy Raja Selvaraj, JIPMER