Table of Contents  

Jamil, Ouda, Jamil, Siddiqui, Malik, and Qureshi: Isolated left ventricular non-compaction syndrome – the first reported case in an Emirati male and review of the literature

Introduction

Isolated ventricular non-compaction cardiomyopathy (IVNC) is a rare and underdiagnosed condition. However, it is gaining prominence as an important, morphologically distinct cause in patients presenting with heart failure. It is characterized by numerous, excessively prominent trabeculations and deep intertrabecular recesses in the left ventricle (LV). The incidence and prevalence of IVNC in the Arab population are unknown. We report on the first adult Emirati male to be diagnosed with this condition.

Case

A 29-year-old man was admitted to Tawam Hospital in Al Ain with symptoms of progressive shortness of breath and congestive heart failure. There was no significant illness in his medical history, nor any family history of heart disease. The patient did not consume alcohol and had no history of foreign travel.

Examination revealed a young, well-built male with a regular heart rate of 120 beats per minute and a blood pressure of 90/60 mmHg. His jugular venous pressure was raised, the apex beat was laterally displaced and a gallop rhythm was audible. Chest examination revealed bibasilar crepitations. There was no ankle oedema.

Metabolic and biochemical workup was negative for any specific aetiology of heart failure. An electrocardiogram showed sinus tachycardia and intraventricular conduction delay with non-specific ST changes. An echocardiogram revealed a dilated left ventricle with severely depressed systolic function and an estimated ejection fraction of 15%. A cardiac computed tomography (CT) angiogram ruled out any coronary artery disease. Careful examination of the echocardiogram and CT scan showed dense and prominent trabecular meshwork with deep intertrabecular recesses at the apex of the heart and in the inferior and lateral walls (Figure 1). This trabecular meshwork was in direct contact with the LV cavity, without evidence of communication to the epicardial coronary artery system.

FIGURE 1

Echocardiogram and CT scan revealing trabecular meshwork with intertrabecular recesses at the apex of the heart and in the inferior and lateral walls. Echocardiographic short-axis (A) and apical four-chamber (B) views of diastolic frames were examined, along with volume-rendered cardiac CT images as shown in (C) and (D), which show spatial relationships more clearly. The longer arrows represent non-compacted, and the shorter arrows compacted, myocardium. These indicate a non-compacted–compacted ratio of > 2, which is diagnostic of IVNC.

6-1-8-fig1.jpg

Hospital treatment was prolonged, and was complicated by ventricular arrhythmias which were difficult to control. Pharmacotherapy with carvedilol, losartan, furosemide, spironolactone and digoxin resulted in an improvement in symptoms. Anticoagulation was commenced, and a single-lead automatic intracardiac defibrillator (AICD) was implanted.

The patient was transferred to a leading cardiac centre in the USA for cardiac transplant workup. As his symptoms were classified as New York Heart Association class II–III, cardiac transplant was deferred and continued medical treatment was recommended. At his 2-year regular follow-up appointment he remained clinically stable. First-degree relatives of the patient were screened for non-compaction. The results were negative.

Discussion

Isolated ventricular non-compaction cardiomyopathy is a congenital cardiomyopathy which, though as yet unclassified by the World Health Organization and the European Society of Cardiology,1,2 is classified as a primary genetic cardiomyopathy by the American Heart Association.3 During early embryogenesis the developmental arrest of the myocardium results in two distinct layers: a thin, compacted epicardial layer and a thick, non-compacted endocardial region. Characterized by excessively prominent trabecular meshwork and deep intertrabecular recesses, this thick, non-compacted region is continuous with the LV cavity,4,5 without evidence of communication to the epicardial coronary artery system.6,7 The recesses are lined by endothelial cells and are histologically different from persistent intramyocardial sinusoids. Thus, the term ‘non-compaction’ rather than ‘persistent sinusoids’ is more appropriate in describing this condition. The term ‘IVNC’ is used in the absence of co-existing congenital lesions. The long-term prognosis and haemodynamic properties of IVNC are largely unknown. This rare disorder of endomyocardial morphogenesis has not yet been studied in the Emirati population.

Pathophysiology

The genetic nature of IVNC is largely unknown. Inheritance is sporadic, and both X-linked and autosomal dominant inheritances have been described in different families.8,9 The aetiology of non-compaction in non-isolated forms may be different.10 Mutations in the G4.5 gene result in a wide spectrum of severe infantile X-linked cardiomyopathic phenotypes, including IVNC with or without Barth syndrome (an X-linked disorder associated with cardiomyopathy, skeletal myopathy and abnormal mitochondria).

Although various theories have been proposed, the exact cause of IVNC remains controversial. Myocardial compaction begins in the septum and base of the heart between the fifth and eighth weeks of embryonic life.11 The congenital theory posits that IVNC results from the failure of compaction at this stage. Other theories point to myocardial tearing due to metabolic defects12 and hypervascularization of the myocardium.

Diagnostic criteria

The characteristic feature of IVNC, crucial for its diagnosis, is the two-layered myocardial wall showing both a thin, compacted epicardial zone and an extremely thickened, non-compacted endocardial zone. Both of these layers are perfused by the epicardial coronary arteries, whereas the deep recesses are filled with blood directly from the LV cavity. Trabeculations are typically located in the apical, inferior and lateral walls.

To improve echocardiographic visualization, the end-systolic thicknesses of both the compacted epicardial and the non-compacted endocardial layers are measured at their thickest points. A non-compacted–compacted (NC/C) ratio of > 2 is diagnostic of this condition.13 For cardiac magnetic resonance imaging, an NC/C ratio of > 2.3 in end-diastole is proposed,14 with sensitivity and specificity of 86% and 99%, respectively.

Hypertrabeculation has also been reported with regards to other forms of cardiomyopathy. A trabeculated LV mass of > 20% of the total LV mass can differentiate IVNC from other causes of LV trabeculations, with sensitivity and specificity of > 90%.15

Clinical features and management

Patients may present with symptoms of heart failure. Arrhythmias which are not directly related to the degree of LV dysfunction are frequent, and may be life-threatening. Thrombus formation in the deep intertrabecular recesses may result in embolic events. The incidence of pulmonary embolism is relatively high,16 suggesting a tendency for thrombosis to occur. Systemic anticoagulation is recommended in such cases, regardless of LV function, to prevent embolic phenomena.17

Management is based on clinical manifestations and is mainly supportive. The most important aspects are the early detection of the abnormality and the prevention of further complications. Standard therapy for heart failure, including angiotensin-converting enzyme inhibitors, beta blockers18,19 and diuretics, is recommended. An AICD is required in patients with arrhythmias, systolic dysfunction or a family history of sudden death.20 Cardiac transplantation is reserved for end-stage disease.

Prognosis is variable, with advanced age, cardiac failure and left ventricular dilatation being predictors of increased mortality.21 Family members should be screened for the condition and counselled regarding the disease process.

A comparison between indigenous and non-indigenous Australian children found a much higher incidence of IVNC in the indigenous children.22 In one study, 13% of healthy black subjects fulfilled echocardiographic criteria for non-compaction.23 These results may reflect a higher incidence in some ethnic groups, or could result from oversensitivity of the diagnostic criteria. The incidence of IVNC in Arab populations is unknown and must be investigated further.

Conclusion

Isolated ventricular non-compaction cardiomyopathy is a disorder of endomyocardial morphogenesis. A distinctive feature is the two-layered structure of the myocardial wall, consisting of a thin, compacted epicardial layer and a thick, non-compacted endocardial layer with prominent trabeculations and deep recesses. Characteristic clinical presentation, diagnostic imaging criteria and pathological pattern make it a distinct cardiomyopathy. Complications include heart failure, systemic embolism and ventricular arrhythmias. Increased awareness and improved imaging has contributed to early and greater recognition of this disease entity. Studies of IVNC in the Arab population are needed to improve our understanding of the prevalence of this syndrome and its incidence in different ethnic groups.

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