A 55-year-old man was referred for evaluation of heart failure. He had been well until three years prior, when he began developing exercise intolerance and atrial arrhythmias. He was admitted for decompensated heart failure and an echocardiogram showed an ejection fraction of 30%. Cardiac catheterization showed non-obstructive coronary artery disease (CAD). His medical therapy was optimized and an implantable cardioverter–defibrillator (ICD) was placed for primary prevention of sudden cardiac death. He was referred for further evaluation of his heart failure and consideration of heart transplantation when he continued to have New York Heart Association (NYHA) class II–III symptoms despite medical therapy.
On examination, his heart rate was 65, blood pressure (BP) 100/65, and he was euvolemic. His cardiac exam demonstrated no murmurs, S3 or S4, and his lungs were clear. His electrocardiogram (ECG) showed normal sinus rhythm with a left bundle branch block. An echocardiogram showed an ejection fraction of 34% with normal valvular function. Prominent trabeculations were noted in the lateral and inferior walls, with hypokinesis in mid-ventricular lateral wall. Apical four-chamber and two-chamber views are shown in Figures 1 and 2. While the appearance suggested of ventricular non-compaction, in some views it was difficult to discern whether there were prominent intertrabecular recesses or ventricular hypertrophy. Therefore, an echocardiographic contrast agent was used to demonstrate the recesses in the apical views shown in Figures 3 and 4. The patient was diagnosed with isolated ventricular non-compaction (IVNC) as the etiology of his cardiomyopathy. In addition to standard heart failure therapy, warfarin was added as prophylaxis against thromboembolic events.
IVNC is a relatively newly recognized cardiomyopathy, first described in a case report in 1984 that described a woman with excessive ‘sinusoids’ in the myocardium on echocardiography.1 Normal embryologic development of the myocardium results in compaction of the wall of the left ventricle with development of extensive endocardial capillaries. The arrest of normal myocardial compaction during embryogenesis results in abnormally trabeculated segments of myocardium with extensive intertrabecular recesses and the normal endocardial capillary bed may be underdeveloped. The hypertrabeculated areas are often hypertrophied or hypokinetic, although the hypokinesis can be seen in wall segments that have seemingly normal compaction.
Heart failure, arrhythmias, and thromboembolic complications are the typical triad of symptoms in patients with IVNC and decreased left ventricular function. Symptoms and the degree of ventricular dysfunction are often related to the extent of non-compaction, with those with more extensive non-compaction demonstrating more symptoms and more significant ventricular dysfunction.
Since the initial description, case reports and clinical series lead to the recognition that the disease is a common cause of cardiomyopathy in children. One study demonstrated >9% of children with cardiomyopathy had IVNC.2 The disorder is not as common in adults, with one series reporting <1% of patients who were referred to a tertiary echocardiography laboratory met criteria for IVNC.3 The 1995 World Health Organization (WHO) classification includes IVNC as one of the ‘unclassified cardiomyopathies’. Currently, the disorder may be under- or overdiagnosed.
Lack of awareness of the entity may lead an echocardiographer to miss the diagnosis, while increasing quality of imaging often identifies prominent trabeculations that may or may not represent a pathologic process.
The diagnosis is made by imaging, and echocardiography is the usual diagnostic modality. Four diagnostic criteria are typically used to make the diagnosis. By definition, co-existing cardiac conditions are absent. The echocardiogram must demonstrate both a thin, compacted layer of myocardium identified and a thicker non-compacted layer, with a ratio of non-compacted to compacted layer thickness at end-systole of >2. The majority of non-compaction is found in the apical and mid-ventricular segments of the inferior and lateral walls. There should be color Doppler evidence of deep intertrabecular recesses.4 Some authors use only the first three criteria,5 although others have demonstrated a high sensitivity and specificity for IVNC compared with other cardiomyopathies if all four criteria are used.6 As seen with our patient, standard 2D echocardiography may be non-diagnostic if the intertrabecular recesses cannot be demonstrated by color Doppler, thus there remains the possibility of apical hypertrophy instead of IVNC. As seen in Figure 3, the use of an echocardiographic contrast agent may allow visualization of the recesses, clarifying the diagnosis, or may demonstrate that color Doppler signals thought to be trabeculations are coronary flow rather than intertrabecular recesses.7
Cardiac magnetic resonance (CMR) imaging can be used for diagnosis; however, the criteria are somewhat different. Rather than the usual nine-segment model of the left ventricle used in echocardiography, the CMR diagnosis is based on a 17-segment model and suggests a ratio of non-compacted to compacted myocardium of 2.3 in diastole is the most accurate criterion for making the diagnosis of IVNC.8 There are also series describing diagnosis made on the basis of ventriculography.
Genetic mutations are associated with non-compaction; however, there is not a single gene mutation yet identified that accounts for the majority of disease. Additionally, while by definition there are not other cardiac disorders in patients with IVNC, there are some data to suggest there may be genetic commonality between IVNC and hypertrophic cardiomyopathy (HCM).9 There is also increasing recognition of a non-compaction phenotype in other disorders, including HCM and congenital heart disease (CHD).
The long-term outcomes are generally poor in symptomatic patients. One series described thromboembolic events in 24% of patients and ventricular tachycardia in over 40% when followed for just over three years.3 Adult patients are treated with usual heart failure therapies, but consideration for anticoagulation should be a standard part of the treatment algorithm. There are not sufficient data to suggest using different criteria for ICD implantation than suggested by current guidelines. While symptomatic patients have significant complications, the prognosis appears better for those patients with evidence of non-compaction but normal left ventricular systolic function.
Our understanding of ventricular non-compaction, the underlying embryologic and genetic abnormalities, the clinical consequences and long-term outcomes and refined diagnostic criteria will continue to improve. Through additional research, we will be better able to distinguish pathology from normal variants, and will be able to refine treatments for those patients with IVNC.