Lights and shadows of implantable cardioverter defibrillators implantations in hypertrophic, dilated and arrhythmogenic right ventricular cardiomyopathies.

In the past decades, implantable cardioverter defibrillators (ICDs) have definitively proved to be superior to antiarrhythmic drugs for the prevention of arrhythmic sudden cardiac death (SCD). Several studies have proved this hypothesis both for primary or secondary (i.e. after a sustained ventricular tachycardia with hemodynamic compromise or ventricular fibrillation) prevention of SCD. However, some complications often occur with ICD implantation, which may be particularly serious for young individuals.

Indications for ICD implantation in young people are mostly ion channel diseases and cardiomyopathies. The latter are structural abnormalities of the myocardium, related to genetic abnormalities, predisposing to malignant ventricular arrhythmias and requiring ICD for the prevention of SCD in some cases.

Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is one of the most common cardiomyopathies and occurs in the 0.2% of the general population¹. It is characterized by localized asymmetrical hypertrophy of the heart and disarray of myocardial cells and filaments. This leads to impaired transmission of electrophysiologic impulses, with an unstable electrical substrate, potentially causing lethal ventricular tachyarrhythmias and SCD.

Short axis view of a cardiac magnetic resonance imaging of a patient affected by hypertrophic cardiomyopathy involving the interventricular septum and the anterior wall of the left ventricle.

ICD implantation in HCM: lights

A minority of patients with HCM are judged to be at increased risk for SCD, whose rate is estimated to be about 1% per year ². However, malignant ventricular arrhythmias remains the most frequent cause of death in this population.

Beta-blockers have failed to demonstrate significant protection from SCD in HCM patients. Type I and III anti-arrhythmic drugs, including amiodarone, have been abandoned because of inefficacy and pro-arrhythmic side effects. Experiences with endocardial and epicardial mapping and ablation in HCM are poor and limited to highly selected patients.

ICDs, conversely, have been proved effective in terminating life-threatening ventricular tachyarrhythmias in HCM and are currently considered the only available tools altering the natural course of the disease and prolonging life.

Appropriate intervention rates of ICD in HCM have been esteemed to be about 11% and 4% for secondary and primary prevention respectively³.

Current recommendation for ICD in HCM

HCM has heterogeneous clinical manifestations in different individuals and a not well predictable clinical course. Targeting HCM-patients for prophylactic ICD implantation can therefore be challenging. However, some “risk factors” have been individuated, that commonly guide the decision for ICD implantation. Current international guidelines recommend ICD in all cases of secondary prevention or when familiar history of SCD, marked left ventricular (LV) hypertrophy or recent unexplained syncopal episodes are present. The role of ICD is uncertain for non-sustained VT or an abnormal blood pressure response with exercise.

ICD implantation in HCM: shadows

Previous studies have reported up to 5.1%/year rate of ICD-related complications in HCM⁴.

The most frequently reported is inappropriate shock delivery, mostly due to erroneous detection and treatment of atrial fibrillation by the ICD. A retrospective study on 334 consecutive HCM patients with an ICD, showed a rate of appropriate vs. inappropriate shock delivery of 2.3 and 4.6%/year⁵. Moreover, a recent meta-analysis involving 2190 ICD-recipients affected by HCM, showed a rate of appropriate vs. inappropriate ICD interventions of 3.3 vs. 4.8%/year respectively⁴.

Another extremely rare complication with ICDs in HCM, is represented by loss of capture due to high pacing thresholds (i.e. energy required for effective right ventricular pacing). This is related to ventricular hypertrophy and may be prevented by accurate individuation of the optimal pacing threshold during ICD programming.

Lengthened mitral valve leaflets, and left ventricular outflow tract obstruction due to LV hypertrophy, also confers a relatively higher risk of infection and endocarditis to HCM patients, which must be considered when an ICD implantation is programmed. Moreover, since ICD implantation in HCM is commonly performed at a relatively young age, patients are supposed to necessitate of a number of interventions for pulse generator substitution over their entire life. For this reason, risk of infection and endocarditis (related to ICD substitutions) is amplified. Eventual needing of ICD and intra-cardiac leads extraction over time must be considered. This is a high-risk procedure, possibly complicated by cardiac tamponade, shock, anemia, arrhythmias or even death.

Finally, ICD implantation can be accompanied by depression, anxiety, reduced quality of life, particularly in young people.

Idiopathic dilated cardiomyopathy

Idiopathic dilated cardiomyopathy (IDCM) is a myocardial disease characterized by LV dilation and systolic dysfunction, commonly resulting in heart failure (HF) and for whom an etiological basis cannot be identified. IDCM is relatively rare (36.5% new cases/year/100.000 persons) but accounts for nearly 10.000 deaths/year in the United States, both due to HF and arrhythmic SCD⁶.

Long axis view of a cardiac magnetic resonance imaging of a patient affected by dilated  cardiomyopathy

ICD implantation in IDCM: lights

ICD are effective for the prevention of SCD in IDCM and can favorably alter the natural course of the disease. Previous studies have showed a rate of appropriate interventions of 5 to 7.5%/year in IDCM-patients with an ICD implanted for primary prevention ^7-8. A large meta-analysis has showed a reduction of mortality with ICD of about 3.5%/year compared to the best medical therapy in IDCM ⁹.

Recommendation for ICD in IDCM

The most important risk factor for ventricular arrhythmias in primary prevention of SCD in IDCM, is represented by severe contractile dysfunction, quantified by the measurement of the ejection fraction (EF) at echocardiography. Functional status, assessed by the New York Heart Association (NYHA) class, also plays a role.

Current international guidelines recommend ICD always for secondary prevention. In case of primary prevention, ICD must be implanted in patients with LVEF ≤35%  and NYHA class II and III¹⁰. However, in a real-life setting, the decision making for patients with IDCM is more complex, because issues such as additional cardiac resynchronization therapy (CRT), co-morbidities, the potential to improve LVEF over time, and eventual genetic etiology also should be considered. With regard to the last issue, carriers of mutations in gene encoding for laminin, are tough to be at increased risk of complete atrio-ventricular block, malignant ventricular arrhythmias and SCD, and may therefore require ICD implantation independently from the EF%.

ICD implantation in IDCM: shadows and warnings

Some shadows obscure the scenario of SCD prevention with ICDs in IDCM.

An important issue regards the high number of patients to be treated in order to save one life because of a currently adopted risk stratification process that appears to lack specificity.

Another topic is the correct timing for ICD implantation for primary prevention. A post hoc analysis of the DEFINITE trials ¹¹ showed that only patients who had received their ICD not later than 3 months after the diagnosis of IDCM would have benefit from implant. However, a significant number of IDCM-individuals show marked improvement of the EF over time, up to values higher than those for which ICD implantation is currently recommended. The goal therefore, appears to be an early and correct individuation of those subjects who will have a negative clinical course, and will therefore require an early ICD implantation for primary prevention.

Similarly to HCM, ICD-related complications have been also reported by various studies, among whom:

1. inappropriate shocks, with consequent reduction of quality of life;
2. infections;
3. risks related to eventual lead extractions;
4. depression and anxiety.

Arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiomyopathy characterized by progressive fibro-fatty replacement of the right ventricular myocardium, sometimes extending also to the left ventricle. The clinical presentation is usually related to ventricular tachycardia (VT) with a left bundle branch block pattern or ventricular fibrillation (VF) leading to SCD. ARVC is a progressive disease ultimately leading to HF.

  Panel A

Panel B

Short (Panel A) and long  axis views (panel B) of a cardiac magnetic resonance imaging of a patient affected by arrhythmogenic right ventricular cardiomyopathy, with evident fibro-fatty replacement of the right ventricle wall, the apex and partial involvement of the left ventricle wall.

ICD implantation in ARVC: lights

The therapeutic options for ventricular arrhythmias in ARVC include catheter ablation and antiarrhythmic drugs such as beta blockers, sotalol and amiodarone. However, these strategies have proved to improve symptoms but not to increase survival. Nowadays, ICD remains the most effective safe-guard against SCD in ARVC.

In a large multicenter international study enrolling ARVC patients with an ICD implanted for primary prevention, appropriate device interventions were observed in one fourth of patients after 5 years. The annual rate of potentially “life-saving” shocks against VF was 3.3% and the estimated benefit of ICD implantation was of 23% after 2 years ¹². Another recent prospective study enrolling a cohort of ARVC patients with an ICD implanted for primary prevention, reported appropriate device interventions in nearly one-half of individuals over a period of 4.7 years ¹³.

Recommendation for ICD in ARVC

As for IDCM and HCM, ICD implantation is recommended in ARVC for secondary prevention (aborted SCD, VF or hemodynamically unstable sustained VT). ICD is also recommended for primary prevention in patients with LVEF≤35%, severe right ventricular dilation and/or dysfunction, a syncopal episode suggestive for VT or VF or an affected family member with SCD. Other risk factors include: non-sustained VT, early onset of the disease and competitive sport activity.

ICD implantation in ARVC: shadows.

Several studies have proved a relatively high incidence of device-related complications in ARVC patients with an implanted ICD. In a study of 132 patients, five individuals required an additional lead because of pacing failure and one patient died from endocarditis secondary to device infection ¹⁴. Progression of fibro-fatty replacement of the myocardial tissue has been associated with high pacing thresholds and impedances and eventual loss of capture. Up to 37% lead-related complication in 7 years have been described in ARVC patients with an implanted ICD ¹⁵.

Considerations

The decision regarding ICD implantation is highly significant for any individual at risk of SCD. The clinical decision-making process itself is complex and imply consideration of a number of different aspects. Despite ICD is the only life-prolonging therapy in cardiomyopathies, eventually associated complications should be considered.

Modern technology, such as that utilized by NayaMed, has currently developed sophisticated algorithms allowing an accurate discrimination of supraventricular from ventricular arrhythmic episodes and properly guiding ICD therapies. A growing knowledge of those algorithms by the cardiologists would hopefully reduce the rate of inappropriately delivered shocks by ICDs.

Reliable RV lead alerts and RV lead integrity algorithms, also a constant automatic measurement of leads’ impedances and P, R Waves amplitude have also been implemented in the ICDs of NayaMed, preventing the problems caused by a lead failure. However, despite such algorithms, a complete abolition of ICD-related complications in cardiomyopathies is unreliable. Therefore, an accurate risk stratification appears necessary, as well as a careful weigh of the relative risks and benefits of ICD implantation in each individual.

Dr. Annamaria Martino
Dr. Leonardo Calo
Policlinico Casilino
Roma, Italy

References

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