Arrhythmia induced Cardiomyopathy (AiCM)

Traditionally, any persistent or frequent episodic tachycardia are known to cause and/or worsen left ventricular (LV) dysfunction and heart failure, which is influenced mainly by the burden, i.e., rate and duration of tachycardia, besides the tachycardia type. Now, there is increased clinical awareness in considering atrial fibrillation (AF) with adequate rate control and premature ventricular contractions (PVCs) as a unique cause of reversible non-ischemic cardiomyopathy.

A more inclusive term of arrhythmia induced cardiomyopathy was suggested to comprise all the three clinical entities-tachycardia-induced cardiomyopathy (T-CM), AF-CM and PVC-CM.¹ Elucidating the pathophysiologic mechanisms underlying each entities is of paramount importance mainly in understanding their long-term potential for complete structural recovery after suppression of the specific inciting arrhythmia.

Tachycardia induced cardiomyopathy (T-CM)

It was first described by Gossage et al. in 1913 in a patient with AF with rapid ventricular response.² It refers solely due to the increase in ventricular rates, regardless of tachycardia origin.

Supraventricular arrhythmias are the most common culprits, namely AF and atrial flutter with rapid ventricular response. Other less common arrhythmias^1,3 known in this context are incessant or recurrent paroxysmal atrial tachycardia (AT), persistent atrioventricular reciprocating tachycardia (AVRT), permanent junctional reciprocating tachycardia (PJRT), rarely dual AV nodal non reentrant tachycardia (DAVNNT) and ventricular tachycardias (VT)-(idiopathic, fascicular).

Myocyte remodelling (Sarcomere loss, abnormal mitochondria, ATPase and beta receptors), Tissue remodelling (Myocyte and ECM disarray and fibrosis) and Electrical remodelling (Calcium mishandling) accompanies T-CM models.⁴

 T-CM demonstrates biventricular dilatation with mild thinning and lack of hypertrophy or change in heart mass (normal LV septal and posterior wall thickness). Unfortunately, after elimination of tachyarrhythmia, recovery of T-CM is not always complete. Ventricular dilation with a hypertrophic response and fibrosis and diastolic dysfunction may persist despite normalisation of LV function.^4,5

Review of various literature^1,6 about T-CM identifies following clinical key points:

1. T-CM should be suspected in patients with LV dysfunction without obvious aetiology. A superimposed T-CM should be considered despite underlying secondary CM (ischemic, infiltrative, or toxic/ drug related), if tachycardia is present.
2. An ambulatory electrocardiogram (ECG) monitor for ≥2 weeks should be considered to confirm or exclude T-CM.

3. A sudden drop of pro-BNP within a week of elimination of tachycardia is supportive of T-CM. But the final diagnosis of T-CM can only be confirmed after recovery or improvement of LV systolic function within 1 to 6 months after elimination of the tachyarrhythmia.

5. In addition to treating tachycardia with antiarrhythmic drugs or radiofrequency ablation, the initial treatment of T-CM should include initiation and optimization of medical therapy for heart failure and LV systolic dysfunction to optimize reverse remodelling.
6. In light of tachycardia recurrence, a permanent treatment such as ablation therapy should be especially considered in arrhythmias with a high success or cure rate

Table 1: Treatment Options of T-CM Based on Tachyarrhythmia

Abbreviations:

AADs-antiarrhythmic drugs; AV-atrioventricular; AVJ-atrioventricular nodal ablation; BB-beta-blockers; PVI-pulmonary vein isolation; T-CM-tachycardia-induced cardiomyopathy; RVR-rapid ventricular response.

Atrial fibrillation induced cardiomyopathy (AF-CM)

AF-CM is defined as LV systolic dysfunction in patients with paroxysmal or persistent AF despite appropriate rate control.

AF-CM may be due to: 1) heart rate irregularity with calcium mishandling; and 2) loss of atrial contraction associated with sympathetic activation contributing to limited ventricular filling and increased filling pressures, functional mitral regurgitation, and diastolic dysfunction.⁷

AF-CM is a diagnosis of exclusion and should be primarily suspected in patients with non-ischemic CM and persistent AF that do not improve after appropriate medical therapy and rate control. Thus, an ambulatory Holter monitor is key to rule out poor rate control and T-CM.

Landmark AF trials with antiarrhythmic drugs have failed to demonstrate outcome benefits including HF admissions in patients with and without HF or CM. This is in contrast to randomized clinical studies comparing AF ablation as a rhythm control versus rate control strategy, which reported an 8-18% absolute increase in LVEF in 60-70% of patients with AF and CM randomized to ablation.^8,9

The only trial comparing rhythm control strategies (ablation vs. amiodarone) in patients with AF and CM demonstrated ablation to be superior by improving freedom of AF (70% vs. 34%), quality of life, HF admissions (31% vs. 57%), and mortality (8% vs. 18%) after 2-year follow-up.¹⁰ Absence of ventricular scar on cardiac magnetic resonance imaging or scar burden <10% may predict reversibility of AF- CM. (CAMERA-MRI)¹¹

PVC induced cardiomyopathy (PVC-CM)

PVC-CM is a diagnosis of exclusion when PVC burden is >10%; however, improvement in LV function may occur with treatment of PVC burden as low as 6%. A prolonged ambulatory ECG monitor (≥6 days), rather than 24-hour Holter monitor, is essential to improve the diagnostic yield of high PVC burden.

A superimposed PVC-CM can be defined as worsening of LVEF by at least 10% due to frequent PVCs in a previously known CM.

LV dyssynchrony (long coupled PVC), loss of AV synchrony due to AV dissociation (shorter coupled PVCs) and sympathetic over activity (variable coupled PVCs) are potential triggers of PVC-CM¹²

The primary cause of contractile dysfunction in PVC-CM appears to be disorders of the calcium-induced calcium release mechanism, with alterations of L-type Ca channel and Ryanodine receptor. There is minimal or no fibrosis on histological examination and on cardiac magnetic resonance imaging.^1,13

Independent predictors of PVC-CM are: male sex, lack of symptoms, duration of palpitations >30 months, variability of PVC coupling interval (dispersion), interpolation of PVCs, coupling interval <450 ms, QRS duration of PVC >150 ms, and epicardial origin.¹⁴

The optimal approach to frequent PVCs (>10% burden) without LV dysfunction, symptoms, or idiopathic ventricular fibrillation is unclear, but patients should probably be monitored every 6-12 months with echocardiography and PVC burden assessment.

A challenge is to identify when PVCs are the aetiology of a CM or just “innocent bystanders” in patients with CM. Patient characteristics, imaging and PVC features help differentiate between these two.¹

 Table 2: Clinical and PVC Features to Identify PVC-CM

There are no randomized prospective studies comparing the efficacy and outcomes between radiofrequency ablation and antiarrhythmic drug therapy, but a retrospective study showed that PVC reduction was greater with radiofrequency ablation than antiarrhythmic drug therapy.¹⁵

References

1. Huizar, JF, Ellenbogen, KA, Tan, AY, Kaszala, K. Arrhythmia-induced cardiomyopathy. J Am Coll Cardiol. 2019;73(18):2328-2344.

2. Gossage, AM, Braxton Hicks, JA. On auricular fibrillation. Q J Med. 1913;6:435-440.

3. Watanabe H, Okamura K, Chinushi M, et al.Clinical characteristics, treatment, and outcome of tachycardia induced cardiomyopathy. Int Heart J 2008;49:39–47.

4. Gupta S, Figueredo VM. Tachycardia mediated cardiomyopathy: pathophysiology, mechanisms, clinical features and management. Int J Cardiol 2014;172:40–6.

5. Spinale FG, Holzgrefe HH, Mukherjee R, et al. LV and myocyte structure and function after early recovery from tachycardia-induced cardiomyopathy. Am J Physiol 1995;268:H836–47.

6. Martin, CA, Lambiase, PD. Pathophysiology, diagnosis and treatment of tachycardiomyopathy. Heart. 2017;103(19):1543-1552.

7. Ling LH, Khammy O, Byrne M, et al. Irregular rhythm adversely influences calcium handling in ventricular myocardium: implications for the interaction between heart failure and atrial fibrillation. Circ Heart Fail 2012;5:786–93.

8. Roy D, Talajic M, Nattel S, et Rhythm control versus rate control for atrialfibrillation and heart failure. N Engl J Med 2008;358: 2667–77.

9. Chen MS, Marrouche NF, Khaykin Y, et al. Pulmonary vein isolation for the treatment of atrial fibrillation in patients with impaired systolic function. J Am Coll Cardiol 2004;43:1004–9.

10. Di Biase L, Mohanty P, Mohanty S, et al. Ablation versus amiodarone for treatment of persistent atrial fibrillation in patients with congestive heart failure and an implanted device: results from the AATAC Multicenter Randomized Trial. Circulation 2016;133:1637–44.

11. Prabhu S, Taylor AJ, Costello BT, et al. Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study. J Am Coll Cardiol 2017;70:1949–61. Potfay J, Kaszala K, Tan AY, et al.

12. Abnormal left ventricular mechanics of ventricular ectopic beats: insights into origin and coupling interval in premature ventricular contraction-induced cardiomyopathy. Circ Arrhythm Electrophysiol 2015;8:1194–200.

13. Hasdemir C, Yuksel A, Camli D, et al. Late gadolinium enhancement CMR in patients with tachycardia-induced cardiomyopathy caused by idiopathic ventricular arrhythmias. Pacing Clin Electrophysiol 2012;35:465–70.

14. Hamon D, Blaye-Felice MS, Bradfield JS, et al. A new combined parameter to predict premature ventricular complexes induced cardiomyopathy: impact and recognition of epicardial origin. J Cardiovasc Electrophysiol 2016;27:709–17.

15. Latchamsetty R, Yokokawa M, Morady F, et al. Multicenter outcomes for catheter ablation of idiopathic premature ventricular complexes. J Am Coll Cardiol EP 2015;1:116–23.

Dr. Sakthivel
Consultant Cardiologist and Electrophysiologist
Kauvery Hospital Chennai