Arrhythmia-induced cardiomyopathy (AIC) refers to left ventricular dysfunction caused by tachyarrhythmias or frequent ectopy. There are two types - type 1 is solely due to the arrhythmia, while type 2 involves an arrhythmia exacerbating an underlying cardiomyopathy. Successful treatment of the arrhythmia via catheter ablation or cardioversion can reverse the left ventricular dysfunction in type 1 AIC. Aggressive treatment with catheter ablation is recommended to eliminate the arrhythmia whenever possible in order to prevent or treat AIC.

1. ARRHYTHMIA INDUCED
CARDIOMYOPATHY (AIC)
DR.K.ABHISHEK

2. INTRODUCTION
• Arrhythmias represent an important reversible cause for left ventricular
Systolic dysfunction.
• Arrhythmias may be under recognized leading to a delay in intervention
• With the advent of catheter ablation treatment options had become easier
• Term arrhythmia-induced cardiomyopathies (AIC) refer to the collective
condition of tachycardia and ectopy‐induced cardiomyopathy.

3. WHAT IS AIC?
• First described in 1913 but it was not well appreciated until 1962 that the reversible nature of
the condition.
• original observations by Philips and Levine in 1949 of the association between rapid AF and a
reversible form of HF
• AIC is a condition in which atrial or ventricular tachyarrhythmias or frequent
ventricular ectopy result in left ventricular (lv) dysfunction, leading to systolic
HF
• Arrhythmia can either be sustained, paroxysmal, or highly frequent ectopic activity.

4. • Arrhythmia duration which preceded the development of lv dysfunction is
often difficult to determine as symptom onset is often insidious with
progressive fatigue and dyspnoea without palpitations.
• Most patients with AIC can expect to improve their LV function to normal
levels with an overall favorable prognosis.
• Nonetheless there is a small risk of sudden cardiac death particularly in the
setting of arrhythmia recurrence or where the cardiomyopathy is of mixed
etiology including coronary disease.

6. TWO CATEGORIES OF AIC
• Type 1 AIC – (arrhythmia induced) when arrhythmia is solely
responsible for AIC and the LV function returns to normal upon successful
treatment of the arrhythmia.
• Type 2 AIC – (arrhythmia mediated) Arrhythmia exacerbates the
underlying cardiomyopathy and treatment of the arrhythmia results in
partial resolution of the cardiomyopathy

7. PATHOPHYSIOLOGY OF AIC
• three mechanisms with considerable overlap between 3 factors
1. Tachycardia
2. Irregular rhythm
3. Dys-synchrony

8. • In animal models ,LV dysfunction is relatively reproducible with rapid
pacing resulting in LV dysfunction within weeks of tachycardia onset.
Three phases have been reported
• Phase 1
Compensatory phase (>7 days). During this phase, there is increased
neurohormonal activation with early changes to the extra cellular
matrix and preserved LV systolic function.

9. • Phase 2- LV dysfunction phase (1-3 weeks).
Continued neurohormonal activation and upregulation of the renin
angiotensin system. There is cellular remodeling, contractile
dysfunction with LV systolic dysfunction and dilatation.
•Phase 3- LV failure phase (>3 weeks).
Further adverse LV remodeling with pump failure, severe dilatation,
and abnormal intracellular calcium handling.

11. Arrhythmia and Patient Characteristics
• rate, duration, rhythm irregularity, persistence and concomitant heart disease
• arrhythmia that is insidious, persistent, and well-tolerated is more likely to result
in AIC
• Lack of persistent tachycardia from autonomic influences and resultant slower
rates during sleep, are likely to be the reason AIC is rare or nonexistent with
inappropriate sinus tachycardia and postural tachycardia syndrome (POTS)
• There is no specific heart rate cutoff at which AIC develops

12. Little is known about patient factors that increase vulnerability to AIC
• homozygous deletion polymorphism in the angiotensin-converting
enzyme gene (DD) had a higher propensity to develop AIC when faced
with persistent tachycardia, suggesting a potential genetic link
• In patients with high PVC burden baseline myocardial fiber disruption
that portends an increased risk to develop AIC

13. Clinical Features
• key diagnostic feature of AIC is the presence of a pathologic tachycardia or
persistent arrhythmia (PVCs) in the presence of an otherwise unexplained
cardiomyopathy
• presentation can be late only after manifest systolic HF develops
• if the arrhythmia is detected early but a nonaggressive approach is taken
progressive worsening of symptoms and insidious development of
cardiomyopathy ensue

14. • History, physical examination, and clinical investigations should focus on
determining the etiology of cardiomyopathy
• Patients with AIC have a smaller LV end-diastolic diameter and mass index versus
those with pre-existing dilated cardiomyopathy and concomitant tachyarrhythmia
• Cardiac magnetic resonance imaging (MRI) may help differentiate AIC from
dilated cardiomyopathy
• Serial assessment of the NT-pro BNP ratio (NT-BNP at baseline/NT-BNP during
follow-up) can differentiate AIC from irreversible dilated cardiomyopathy

15. AIC Associated with Specific Arrhythmias in Adults
• Atrial Fibrillation
• Atrial Flutter
• Supraventricular Tachycardias
• PVCs and Ventricular Tachycardia

16. AF‐MEDIATED CARDIOMYOPATHY
• most common cause of AIC in adults
• AF and HF are modern epidemics which often coexist and precipitate one
another.
• Factors responsible are - tachycardia, heart rate irregularity, loss of atrial
systolic function, and genetic factors
• Irregular contraction leads to adverse hemodynamic consequences that are
independent of heart rate

17. • irregularity is demonstrated in patients with rate controlled AF and LV
dysfunction, who improve LV function following atrioventricular nodal
ablation which regularizes ventricular rhythm with pacing.
• atrioventricular dys synchrony can impair diastolic filling which in turn
worsens diastolic function thereby leading to increased left sided pressure
and negative atrial remodeling which in turn perpetuates AF
• Coordinated atrial contraction contributes up to 20% of cardiac output and
loss of atrial contraction adversely affects cardiac output in AF

18. • Until recently rate control was thought to be adequate in the management
of AF‐induced AIC.
• The AF‐CHF trial did not show a survival advantage in patients with NYHA
class 2/3 heart failure symptoms and LVEF < 35% randomized to
pharmacologic rate control vs rhythm control.
• multiple randomized studies showed , with catheter ablation as the rhythm
control strategy have demonstrated the superiority of restoring sinus
rhythm when compared with pharmacologic therapy

19. • A systematic review of 19 studies (914 patients) showed a 13.3% (95% CI 115 to
16%) improvement in LV EF in patients who underwent catheter ablation to
restore sinus rhythm
• Although current heart failure guidelines are yet to include AF ablation in people
with HF this is likely to change particularly in light of the recent CAMERA‐MRI
and CASTLE‐AF trials(land mark trail)
• These 2 significant trials demonstrate the importance of restoration of sinus
rhythm with catheter ablation in patients with AF and systolic heart failure with
improvements in LVEF, quality of life, failure hospitalization and total mortality

20. Atrial Flutter
• more difficult to rate control than AF, given less concealed conduction into the AV
node
• despite intense efforts at pharmacological rate control minimal exertion can lead
to rapid ventricular rates
• high success rate and low risk of complications with catheter ablation
• ablation to eliminate atrial flutter is recommended when AIC is suspected
• in whom catheter ablation is not feasible or desired, cardioversion with
antiarrhythmic therapy

21. Supraventricular Tachycardias
• Persistent supraventricular tachycardias can result in AIC by several
mechanisms
• catheter ablation should be pursued whenever possible as first-line
therapy for supraventricular tachycardia-mediated AIC
• Successful catheter ablation can normalize LVEF and is usually
associated with excellent long-term outcomes

22. PVCs and Ventricular Tachycardia  AIC
• Idiopathic ventricular tachycardia and frequent PVCs (MC) can lead to AIC
in patients without structural heart disease and can exacerbate
cardiomyopathy in patients with structural disease
• PVCs associated with cardiomyopathy usually arise in the right or left
ventricular outflow tract
• but PVCs from non-outflow tract sites can also result in AIC
• mechanism of PVC-mediated AIC is not fully understood

23. • Potential mechanisms postulated include ventricular dys-synchrony, especially
related to LBBB PVC morphology, abnormal calcium handling from the short
coupling intervals, and abnormal ventricular filling from the post-PVC pause
• A high PVC burden has been variably defined as ranging from >10,000 to 25,000
PVCs/day and as >10% to 24% of total heartbeats/day
• There appears to be a threshold burden of ~10,000 PVCs/day for developing AIC
• Ventricular function can improve if the PVC burden is reduced to <5,000/day
• This is an important target when elimination of all PVCs may not be possible,
especially in the setting of multiform PVCs.

24. • Therapy for PVC-mediated AIC should be targeted at suppressing or eliminating
the PVCs, and include antiarrhythmic therapy and catheter ablation
• Beta-blockade and non-dihydropyridine calcium channel blockade are low-risk
therapies (LIMITED effectiveness)
• Dofetilide, mexiletine, sotalol, or amiodarone may be more effective, although
with greater risk of side effects and proarrhythmia
• Catheter ablation has emerged as the definitive therapy for PVC-mediated AIC,
with success rates ranging from 70% to 90%

25. • Elimination of PVCs with ablation has been shown to improve LVEF,
ventricular dimensions, mitral regurgitation, and functional status.
• In an observational series, ablation was superior to antiarrhythmic therapy
in reducing PVCs and improving LVEF
• Successful ablation of PVCs can improve the efficacy of cardiac
resynchronization therapy in nonresponders
• The elimination of high PVC burden (>10%) in patients with impaired LVEF
can be associated with improvement of function, even when structural
cardiac abnormalities are present

26. Management in Adults–Summary
• attempt careful and aggressive control of rate and rhythm
• focus on arrhythmia elimination by catheter ablation whenever possible.
• The only tachyarrhythmias that do not appear to require aggressive
treatment to prevent AIC are sinus tachycardia and POTS.
• Continued therapy with neurohormonal antagonists is advisable for
favorable remodeling, although the duration of such therapy is not well-
defined .

27. AIC in Children
• AET (59%) and permanent junctional reciprocating tachycardia (PJRT 23%)
were the most common arrhythmias represented
• Ventricular arrhythmias were uncommon
• Tachyarrhythmias are a reversible cause of cardiomyopathy from fetal life
• Children often present late because they fail to recognize palpitations or are
unable to verbalize symptoms and come to medical attention only after the
development of HF

28. • In children tachycardias most often associated with AIC have a narrow QRS
complex and 1:1 AV conduction.
• Heart rate irregularity occurs in pediatric AIC, but as salvos of tachycardia
interspersed with periods of sinus rhythm, rather than as the persistent
heart rate irregularity seen in AF.
• Genetic factors Serum- and glucocorticoid-regulated kinase-1 (SGK1), a
component of the cardiac phosphatidylinositol 3-kinase signalling pathway
has proarrhythmic effects and has been linked to biochemical and
functional changes in the cardiac sodium (Na+) channel

29. • treatment with ranolazine, which blocks the late Na+ current
• Conversely, inhibition of SGK1 in the heart protects against fibrosis,
HF, and Na+ channel alterations after hemodynamic stress

30. Pediatric Arrhythmias Associated with AIC
• Atrial Ectopic Tachycardia
• Permanent Junctional Reciprocating Tachycardia
• Junctional Ectopic Tachycardia
• Ventricular Tachycardia and PVCs

31. Atrial Ectopic Tachycardia
• most common arrhythmia associated with AIC in children
• Increased automaticity is the most likely mechanism; others include
triggered activity and micro-reentry
• AET usually occurs without structural heart disease, but has been
described after congenital heart disease surgery and in the setting of
channelopathies

32. • beta-blockers being the most common first-line therapy
• Catheter ablation was effective in 81% .
• use of electro-anatomical mapping for ablation improved success and
decreased recurrence
• Spontaneous resolution of AET can occur, especially in those
presenting within the first year of life( 74% )

33. Permanent Junctional Reciprocating Tachycardia
• PJRT is an accessory pathway-mediated tachycardia with a long RP interval
and occurs predominantly in infants and children
• pathway can be located anywhere in the AV junction, but is usually
postero-septal
• Pathways are tortuous and slow-conducting which makes it incessant
• clinical course of PJRT is not benign and spontaneous resolution is unlikely
• Beta-blockers are the common first choice

34. • Complete tachycardia suppression with medications varies from 25%
in the recent series to >80% in a study using regimens that included
amiodarone
• Medical therapy is commonly employed in neonates and infants,
whereas older children undergo ablation.
• Catheter ablation is the primary treatment for PJRT with reported
success rates of 90%

35. Junctional Ectopic Tachycardia
• commonly seen in small children following congenital heart surgery
• due to abnormal automaticity in the region of the AV junction
• JET unassociated with cardiac surgery can present at any age, and congenital
JET, presenting in infancy, is associated with high morbidity and mortality
• Beta-blockers were the most common first-line agent, but the majority
required ≥2 drugs for control

36. • complete suppression seen in only 11%. Amiodarone alone or in
combination was cited as the most effective for rate or rhythm
control
• Catheter ablation for JET can be accomplished with the preservation
of AV nodal conduction and cryoablation has been associated with
success rates similar to radiofrequency ablation, but without AV block

37. Ventricular Tachycardia and PVCs
• rare in children, ventricular tachycardia can result in AIC.
• Incessant ventricular tachycardia of infancy occurs in association with
ventricular Purkinje cell tumors or histiocytoid or lymphocytoid
tumors
• Both left and right ventricular tachycardias can result in pediatric AIC

38. AIC in Children–Summary
• Tachyarrhythmias resulting in AIC in children differ from those in the
adult
• There is a predictable pattern of resolution with the median time to
recovery in a larger study was <2 months
• Recovery seems independent of treatment strategy ablation vs
medical therapy

40. MANAGEMENT OF AIC

41. TAKE HOME
• It is highly likely that the incidence of AIC (arrhythmia- induced cardiomyopathy) is
underestimated in general as well as in patients with unexplained left ventricular systolic
dysfunction or idiopathic dilated cardiomyopathy.
• The evidence for the pathogenesis and clinical management of AIC is predominantly
based on animal models and retrospective clinical analyses with limited case numbers.
• Diagnosis focuses on identifying a potential underlying arrhythmia in otherwise
unexplainable left ventricular systolic dysfunction.
• Even if the ventricular rate is normal, persistent arrhythmias such as atrial fibrillation or
frequent premature ventricular contractions can cause AIC

42. • Therapy of AIC consists of treating the triggering arrhythmia (accompanied by
guideline-compliant heart failure medication).
• The diagnosis of AIC is confirmed if left ventricular pump function normalizes over
the following weeks or months.
• Close follow-up is recommended, given that arrhythmia recurrence following
primarily successful treatment of AIC can lead to a renewed and rapid
deterioration in left ventricular pump function
• Reports of sudden death in patients whose left ventricular ejection fraction have
raised doubt on the complete reversibility of this condition

43. • THANK YOU