Progressive left ventricular noncompaction and systolic dysfunction

Abstract

Left ventricular noncompaction is a condition characterized by prominent ventricular trabeculations, often accompanied by systolic dysfunction. The present case involves an adult with a small ventricular septal defect, initially exhibiting mild systolic dysfunction and slightly prominent left ventricular trabeculations progressing over 13 years to severe dilated cardiomyopathy and overt noncompaction. The present case strongly suggests a correlation between the extent of noncompaction and the degree of systolic dysfunction. The initial presence of a small ventricular septal defect and mild trabeculations highlights the genetic determinants of non-compaction and the importance of closely following patients with mild noncompaction due to the possibility of progression. More sensitive diagnostic criteria are needed to avoid overlooking mild cases, which may show prominent trabeculations without reaching a requisite ratio of compacted to noncompacted tissue.

Left ventricular noncompaction (LVNC) is an under-recognized cardiac abnormality characterized by prominent ventricular trabeculations and deep intertrabecular recesses, usually accompanied by impaired systolic function (1). The estimated prevalence of LVNC ranges from 0.01% to 0.27%, with more recent studies generally reporting higher prevalence, likely due to increasing awareness of the condition (2). Symptoms vary, the most common including exertional dyspnea, anginal chest pain, palpitations and edema (3–5). The progression of LVNC is also highly variable: in rare cases, regression of noncompaction has been observed (6,7), whereas other cases are associated with serious complications including heart failure, life-threatening ventricular arrhythmia and cardioembolism. We present a case of mildly prominent trabeculations in a patient with a small ventricular septal defect (VSD), progressing to severe dilated cardiomyopathy with a dramatic increase in noncompaction localized to the free wall of the left ventricle.

CASE PRESENTATION

A generally healthy 63-year-old woman presented in June 2011 with increasing peripheral edema and a two-week history of exertional dyspnea that was most noticeable while climbing stairs. She denied chest pain, palpitations, syncope or dyspnea at rest. Her medical history included hyperlipidemia (controlled with a statin) and a hemodynamically insignificant congenital ventricular septal defect. She had no history of coronary artery disease, hypertension, diabetes, smoking, heavy alcohol use or illicit drug use. Her family history was significant for a myocardial infarction and a cerebrovascular accident, both in her father. There was no family history of congenital heart disease or cardiomyopathy.

An electrocardiogram revealed sinus rhythm with premature ventricular and atrial complexes and inferolateral ST depression. A review of records revealed that transthoracic echocardiograms (TTEs) were performed in 1998 and 2002, showing normal left ventricular diameters of 51 mm and 53 mm, and mild prominence of left ventricular trabeculations, with a ratio of noncompacted to compacted myocardium (NC/C) of 1 (Figure 1). There was a decline in left ventricular ejection fraction from 45% to 50%, to 35% to 40% over the four-year interval between studies. A small VSD was visible only by colour flow Doppler, with a pulmonary to systemic flow ratio (Qp/Qs) of 1.2. Other TTE findings included trace mitral regurgitation, trace tricuspid regurgitation and a calculated pulmonary artery pressure of 23 mmHg. Cardiac catheterization was not performed at that time. The patient was lost to follow-up for nine years and, on her presentation in 2012, her TTE showed left ventricular dilation to 60 mm and a marked increase in trabeculations. There was a bilayered appearance with a thick trabeculated endocardial layer and a thin compacted epicardial layer (NC/C=3) consistent with LVNC (Figure 2). The ejection fraction had decreased to 15% to 20%, and the pulmonary artery pressure as measured by TEE had increased to 40 mmHg, likely secondary to low cardiac output. Additional findings included 2+ mitral regurgitation, 2+ tricuspid regurgitation and interval closure of the VSD.

Figure 1).

Two-dimensional echocardiogram four-chamber view obtained from the patient in 2002 showing a normal size left ventricle with mild trabeculations and an estimated ejection fraction of 35% to 40%. LV Left ventricle; RV Right ventricle

Figure 2).

Repeat two-dimensional echocardiogram obtained in 2011 showing mild enlargement of the left ventricle and prominent trabeculations with sinuses consistent with noncompacted myocardium of the lateral wall. The septal and anterior walls were thin and akinetic. The ejection fraction was estimated to be 15% to 20%

Cardiac catheterization was performed, revealing minimal coronary artery disease, global left ventricular hypokinesis, an ejection fraction of 15% and a cardiac index of 2.35 L/min/m². There was mild pulmonary artery hypertension (47 mmHg) without a significant step-up in right sided oxygen saturations. The mean capillary wedge pressure was 8 mmHg and the pulmonary vascular resistance was 38.1 dynes/cm².

Because there is no specific treatment for LVNC, management was directed at controlling the patient’s symptoms and reducing the morbidity of her heart failure. She was treated with furosemide, lisinopril, and metoprolol, with resultant improvement in her edema and dyspnea.

DISCUSSION

The present case demonstrates a significant increase in noncompacted myocardium corresponding to worsening systolic dysfunction over a period of 13 years. The initial TTEs showed more prominent trabeculations than expected in a normal heart, but not sufficient to be labelled as LVNC by the most accepted diagnostic criteria requiring an NC/C ratio ≥2 (8). The progression of the patient’s disease suggests a need for more sensitive diagnostic criteria to avoid overlooking cases of early LVNC, which may have significant consequences over time. Belanger et al (9) proposed a scheme that classifies noncompaction according to severity, identifying prominent left ventricular trabeculations with NC/C <2 as mild or moderate LVNC. This type of classification scheme may have been appropriate for early diagnosis of the present patient, in whom LVNC was only retrospectively identified as a likely contributor to systolic dysfunction.

The etiology of LVNC is currently speculative. The majority of documented cases are congenital, the prevailing theory being that the normal process of myocardial compaction is arrested during embryonic development, resulting in an excess of immature trabeculated myocardium (10). There is a smaller body of evidence that LVNC in some cases is acquired in adulthood, possibly as a compensatory response to an impaired myocardium (11–13).

The extent of LVNC and prognosis appears to correlate with the degree of systolic dysfunction (14), with one study finding a trend toward a negative linear correlation between NC/C ratio and left ventricular ejection fraction (9), and another reporting that increased mortality was related to the presence of heart failure and reduced left ventricular fractional shortening (15). These data are supported by the present case, in which the progression of LVNC corresponded to a significant decline in ejection fraction. The sequence of TTEs indicates that a mild form of noncompaction existed in the early stages of systolic dysfunction but before the development of dilated cardiomyopathy, suggesting that LVNC may have been the primary cause of heart failure. Alternatively, an idiopathic dilated cardiomyopathy could have been the primary disease and the progression of non-compaction may represent a compensatory response to worsening systolic dysfunction, although this is less likely given that mild noncompaction and systolic dysfunction were present before left ventricular dilation.

LVNC frequently occurs in conjunction with one or more congenital cardiac anomalies, including ventricular septal defects, atrial septal defects, valvular abnormalities, coarctation of the aorta and anomalous pulmonary veins (16,17). In a small pediatric study (17), the authors reported VSD in four of 14 patients with LVNC; however, larger studies are needed to establish the prevalence of VSD among patients with LVNC. It is unknown whether there is a causal link between certain genetic abnormalities and LVNC, but associations have been noted with hypertrophic and dilated cardiomyopathies, neuromuscular disorders, other hereditary disorders and chromosomal aberrations (2).

Management of LVNC is currently focused on control of symptoms and prevention of complications (ie, treatment of heart failure, management of arrhythmias, implantable cardioverter defibrillator placement if appropriate and anticoagulation to prevent cardioemboli). There have been case reports of LVNC regressing in patients receiving appropriate treatment (6,7); however, there is not enough evidence to indicate that therapy influences the course of noncompaction. The present case raises the question of whether the progression of non-compaction could have been avoided or delayed if the patient had undergone earlier treatment for systolic dysfunction.

CONCLUSION

Mild noncompaction can progress over time and should be followed closely. There is a need for more sensitive diagnostic criteria for LVNC because mildly abnormal trabeculations may be overlooked if the observer relies on an arbitrary requirement of NC/C ≥2. As suggested by other authors, a subdiagnostic NC/C ratio should not preclude the recognition of LVNC if a clearly two-layered myocardium is present (2,9). Genetic testing and screening of family members may be useful tools for early detection of LVNC given its association with hereditary disorders and chromosomal aberrations. Due to the frequent association of LVNC with cardiac defects, the presence of LVNC should raise suspicion for other cardiac abnormalities and vice versa. The effect of optimal therapy on the progression of noncompaction is unknown, but there exists the possibility of delaying progression or inducing regression of LVNC.