The Risk of Sudden Cardiac Death in a Patient With Non-Compaction Cardiomyopathy

Case Description

A 35-year-old male with past medical history of depression and remote methamphetamine and alcohol abuse was referred for electrophysiological consultation for possible implantable cardioverter defibrillator (ICD) placement after resuscitated cardiac arrest four months ago. According to emergency department notes, the patient collapsed at home and his friend called 911. First responders found the patient unresponsive with agonal breathing; they applied an AED, which advised CPR. The fire department squad performed CPR for 20 minutes until an ambulance arrived. CPR was continued en route to the hospital, until the patient regained a pulse. The initial rhythm was documented as asystole without mention of any defibrillation attempts. No rhythm strips from the ambulance were available for review. In the emergency department, the patient was intubated and started on hypothermia protocol. Computed tomography (CT) of the chest ruled out pulmonary embolus and showed bilateral pulmonary infiltrates. The patient was subsequently treated in the ICU for bilateral pneumonia and possible septic shock. He experienced a complete neurological recovery. Transthoracic echocardiogram (TTE) demonstrated moderate concentric left ventricular hypertrophy (LVH) without dilation and severely reduced global systolic function with an LV ejection fraction (LVEF) of 20%-25%. A few days later, coronary angiogram showed normal epicardial coronary arteries with an LVEF of 30%-35%. The patient was discharged with the LifeVest wearable defibrillator (ZOLL Medical Corporation) and medical therapy for non-ischemic cardiomyopathy. 

Three months later, repeat TTE showed further improvement in LVEF to 40%-45%. The patient had completely recovered and was requesting a clearance to return to his work, which involved heavy lifting and commercial truck driving. His physical exam was unremarkable except for 2/6 systolic murmur on apex. He reported being in a normal state of health prior to cardiac arrest. The patient denied prior history of syncopal episodes, family history of sudden cardiac death, and a personal or family history of heart disease. He had a prior history of polysubstance abuse, but claimed abstinence for several years. He was unable to tolerate an angiotensin-converting enzyme (ACE) inhibitor due to hypotension, and was taking only 3.125 mg of carvedilol. EKG showed sinus tachycardia at 95 bpm with prolonged PR interval at 220 ms (Figure 1). The cause of cardiomyopathy was not clear and was initially suspected to be a viral myocarditis, alcohol/drug-induced, or idiopathic dilated cardiomyopathy. The patient was extremely hesitant to have an ICD implanted because it would lead to loss of employment and possibly a need to apply for disability. Therefore, further workup was planned including an EP study and referral to a tertiary center for cardiac MRI. EP study revealed abnormal atrioventricular (AV) nodal conduction with AV block cycle length of 580 ms. Aggressive programmed ventricular stimulation from the right ventricular apex and outflow tract failed to induce sustained monomorphic ventricular tachycardia (VT) or ventricular fibrillation (VF). However, cardiac MRI revealed left ventricular non-compaction cardiomyopathy (LVNC) with an ejection fraction of 40% and mid-septal scar with late gadolinium enhancement. Given the finding of non-compaction cardiomyopathy with a history of prior cardiac arrest and abnormal AV nodal conduction, implantation of a dual-chamber ICD was recommended. Echocardiographic screening of first-degree relatives was also advised. The diagnosis of LVNC was missed in this patient on TTE due to suboptimal endocardial visualization.

Discussion

This was an interesting case of a patient who had a history of documented asystolic arrest and mild left ventricular systolic dysfunction who was referred for evaluation of ICD implant and clearance for work. The diagnosis of non-compaction cardiomyopathy was established by cardiac MRI. 

LVNC was previously associated with various congenital heart malformations; it was only recently separated into a distinct form of cardiomyopathy. LVNC carries a substantial risk of heart failure, ventricular and atrial arrhythmias, sudden cardiac death, and systemic thromboembolism. LVNC is caused by the intrauterine arrest of the normal maturation (compaction) process of myocardial fibers in the ventricular endocardium. This results in a two-layered myocardium, consisting of a thin compacted epicardial layer and a spongy endocardial layer with numerous prominent trabeculations and deep intertrabecular recesses. Temporal variability of myocardial maturation failure may explain the large spectrum of pathological and clinical manifestations of the disease. LVNC is most evident in the apical and mid-lateral/inferior portions of the left ventricle. LVNC may present as an isolated non-compaction with normal LV size and function with or without ventricular arrhythmias, the dilated form with systolic dysfunction, a hypertrophic form mimicking hypertrophic cardiomyopathy, mixed hypertrophic and dilated form, or the restrictive form similar to restrictive cardiomyopathy. The size, thickness, or function of the myocardium in LVNC may change unexpectedly (“undulating phenotype”).^1,2

LVNC is associated with both sporadic and familial cases. Approximately 30%-40% of LVNC patients had inherited LVNC.³ Inheritance most commonly follows an autosomal dominant or X-linked pattern. Mutations in approximately 15 genes have been implicated with sarcomere-encoding genes being most common.³

The diagnosis is generally established by TTE, and is based on findings of a two-layered myocardium with a thin, compacted epicardial layer and a thick endocardial layer with prominent trabeculations and recesses. Differentiation of LVNC from normal patterns may be difficult. Criteria from Jenni et al use an end systolic ratio of non-compacted to compacted layers of at least 2 in short-axis view. Additional criteria include color Doppler evidence of deep intertrabecular recesses, predominant localization of non-compaction in the lateral, apical or inferior walls of the LV, and the absence of coexisting cardiac abnormalities.⁴ 

Cardiac magnetic resonance imaging is the best confirmation tool. In contrast to echocardiography, it uses diastolic criteria. The presence of late gadolinium enhancement on cardiovascular magnetic resonance has been associated with more severe clinical disease.¹

EKG frequently shows intraventricular conduction delay such as left bundle branch block, LV hypertrophy, and repolarization abnormalities. EKG abnormalities are associated with systolic dysfunction and systemic embolic events.⁵

The clinical manifestations of LVNC are highly variable, ranging from asymptomatic to progressive heart failure and recurrent or life-threatening arrhythmias, and thromboembolic events.^1,2 

Ventricular arrhythmias are hallmark of LVNC. Sustained and non-sustained monomorphic VTs are most common, though polymorphic VT, bundle branch reentry, RVOT, fascicular VT, and VF have been described. VT is found in 38%-47% of affected individuals, with sudden cardiac death (SCD) accounting for a significant portion of the mortality.⁵ Proposed substrates for arrhythmias include the areas of slow conduction in the intratrabecular crypts and a subendocardial fibrosis within the non-compacted myocardium. Atrial arrhythmias are common, with atrial fibrillation predominantly seen in adults and AV reentrant tachycardia or focal atrial tachycardia in children.⁵
Bradyarrhythmias range from sinus bradycardia to varying degrees of AV block including complete heart block.⁵

Management of patients with LVNC focuses on prevention and treatment of heart failure, arrhythmias, and thromboembolism.

Patients that would benefit from ICD implantation include those with a history of aborted cardiac arrest or ventricular arrhythmias refractory to antiarrhythmic therapy and/or not amenable to ablation.^2,5

Because of the high prevalence of supraventricular arrhythmias and the need for pacing support for bradyarrhythmias, a dual-chamber device should be considered.⁵

Risk factors for SCD include an increased LV dimension, decreased LV systolic function, heart failure (NYHA class III/IV), ventricular arrhythmia, and atrial fibrillation. Inability to induce VT with programmed ventricular stimulation has limited negative predictive value.⁵

Genetic testing can be useful for patients with an established clinical diagnosis of LVNC. Mutation-specific genetic testing is recommended for family members and appropriate relatives following the identification of an LVNC-causative mutation in the index case. All first-degree relatives of a patient with LVNC should be evaluated echocardiographically.³

Conclusion

This case illustrates the important role of cardiac MRI for risk stratification of a patient with documented asystolic cardiac arrest and non-ischemic cardiomyopathy. ACC/AHA/HRS guidelines define a VF/VT arrest in the absence of reversible cause as a class I indication for secondary prevention of sudden death.⁶ However, determination of the initial rhythm can be difficult because of spontaneous changes between VF/VT and non-tachyarrhythmic mechanisms. For example, the time between onset of a VF/VT and deterioration to asystole or pulseless electrical activity can be brief, and initial VF/VT could have been missed due to delayed arrival of EMS. Establishing a diagnosis of non-compaction cardiomyopathy in this patient with a prior history of asystolic cardiac arrest allowed us to better assess the risk for sudden death and more confidently recommend ICD implantation. 

Disclosure: The author has no conflicts of interest to report regarding the content herein. Outside the submitted work, Dr. Kamalov reports consulting fees from Biosense Webster.

References

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