Introduction
Noncompaction of the Ventricular Myocardium (NVM) is currently considered to be a cardiomyopathy caused by arrested development of the endocardium and myocardial layer during embryonic development, often in conjunction with other congenital heart diseases, or alone. It may be clinically asymptomatic or may present with heart failure, arrhythmias, or thromboembolism of the body circulation, and echocardiography is the primary method of diagnosis. It is often misdiagnosed or missed clinically due to similarity to other cardiomyopathies and lack of awareness of the disease.
Embryology
Early in embryonic development, the myocardium is a loose meshwork of longitudinal and transverse fibers with intervening deep cryptic foci that communicate with the ventricular chambers. Between 5 and 8 weeks of embryonic development, this sponge-like fibrous meshwork of myocardium undergoes slow densification from epicardium to endocardium and from base to apex, while the inter-trabecular crypt evolves into capillaries that participate in the formation of the coronary circulation. Developmental arrest during this period can lead to NVM (Figure 1).
Types
NVM is initially found in congenital heart diseases, such as right or left ventricular outflow tract stenosis, complex cyanotic precordial disease, or coronary artery malformations, where the etiology may be related to increased pressure loading of the cardiac chambers or myocardial ischemia blocking the embryonic development of the sinusoidal gap. The deep sunken crypt communicates with both the ventricular cavity and the coronary circulation.
Isolated NVM (INVM) presents with persistent embryonic myocardial morphology without other cardiac malformations. INVM is classified as an unclassified cardiomyopathy in the World Health Organization classification.
The left ventricle is usually involved, but biventricular densification insufficiency has also been reported. Right ventricular involvement is seen in less than half of patients. Because of the well-developed right ventricular myocardial trabeculae, it is difficult to distinguish between a normal and an insufficiently densified right ventricle, so some scholars question whether a true right ventricular densification insufficiency exists.
Histology
INVM may present with interstitial myocardial fibrosis, endocardial thickening, and elastic fiber hyperplasia. In addition, necrotic cardiomyocytes can be seen in the thick myocardial trabeculae of incomplete densification.
Genetics
The family recurrence rate of INVM is approximately 50% in children and 18% in adults (possibly related to incomplete follow-up). INVM is currently thought to be X-chromosome linked, with mutations in the G4.5 gene on Xq28 causing INVM, but mutations at this locus are also seen in other myopathies involving the heart, such as Barth syndrome, Emery-Dreifuss myotonic dystrophy, and myotubular myopathy.
Epidemiology
INVM is seen in children and adults, even in the elderly. the prevalence in the general population is not known, with a detection rate of 0.014% in the echocardiographic laboratory. The proportion of males is higher than that of females, ranging from approximately 56% to 82%.
Clinical features
The clinical presentation of INVM varies in severity, with heart failure, arrhythmias and thromboembolism in severe cases.
1. Heart failure
INVM may be asymptomatic in mild cases and may manifest as disabling heart failure in severe cases. More than 2/3 of patients have symptoms of cardiac insufficiency and may have systolic and diastolic insufficiency. Hemodynamic performance on cardiac catheterization may resemble restrictive cardiomyopathy, and INVM in children may initially present as restrictive cardiomyopathy. Systolic insufficiency may be associated with inadequate subendocardial myocardial perfusion and impaired microcirculation, and decreased coronary flow reserve may be seen not only in underdense segments but also in “normal” myocardium.
2. Arrhythmias
INVM is often associated with various types of arrhythmias. 25% of adult patients have atrial fibrillation as a complication. The incidence of ventricular tachycardia can be as high as 47%, and half of the deaths are sudden cardiac deaths, but ventricular tachycardia and sudden death are rare in children. In addition, paroxysmal supraventricular tachycardia and complete atrioventricular block are also seen in patients with IVNM. Most patients have resting ECG abnormalities that are not specific, including left ventricular hypertrophy, repolarization abnormalities, T-wave inversion, ST-segment changes, electrical axis shift, intraventricular block, and complete AV block. 44% of adult patients have left bundle branch block, but it is less common in children. Pre-excitation syndrome is present in up to 15% of children, but is rare in adults.
3. Thromboembolism
The incidence of thromboembolism in INVM ranges from 21% to 38% and is associated with intraventricular thrombosis, reduced systolic function, and atrial fibrillation, which can cause cerebral infarction, transient ischemic attack, pulmonary infarction, and mesenteric infarction. However, thromboembolism in children has not been reported.
4.Facial deformity
Pediatric patients may have special facial features: prominent forehead, low-set ears, strabismus, high arch of the palate, and small deformities.
Diagnosis
The diagnosis of INVM relies mainly on echocardiography. Two-dimensional echocardiography reveals coarse myocardial trabeculae on the surface of the ventricular cavity and deep sunken crypt between the trabeculae, and color Doppler can show that these crypt have blood flow traffic with the ventricular cavity (Figure 2). The diagnosis of IVNM is made after exclusion of semilunar stenosis and coronary artery malformation.
The segments most commonly involved in INVM include the left ventricular apical, inferior, and intermediate segments of the lateral wall, and the right ventricular apical region may also be involved. Systolic function is often significantly reduced in the left ventricle, and the flow spectrum through the mitral valve and pulmonary veins often shows impaired diastolic function and restrictive hemodynamic changes. Ventricular wall hypokinesis is seen in both densified and normal segments.
The quantitative diagnosis of INVM can be obtained by measuring the ratio of X to Y at the mitral, papillary muscle, and apical levels, with X representing the distance from the epicardial surface to the base of the trabecular saphenous fossa and Y representing the distance from the epicardial surface to the tip of the trabeculae; the smaller the ratio the more severe the densification insufficiency, with higher diagnostic value at the papillary muscle and apical levels, but often with operator variability at the apical level. Another method is to divide the abnormally thickened myocardium into two layers: the outer layer of normally densified myocardium and the inner layer of comb-like thickened myocardium. The ratio of the maximum thickness of the end-systolic non-dense layer to the normal myocardial layer is measured and calculated on a parasternal short-axis view, and a ratio of more than 2 is used as a criterion for the quantitative diagnosis of INVM.
Transesophageal echocardiography and cardiac sonography are indicated when the quality of transthoracic images is poor. Other diagnostic imaging methods include CT, MRI, and ventriculography. MRI correlates well with ultrasound in the localization and quantitative diagnosis of myocardial densification insufficiency, and differences in MRI signal intensity predict the risk of fatal arrhythmias. Invasive electrophysiological examinations are not commonly performed in clinical practice. Signal-averaged electrocardiograms can show changes in late potentials and QT dispersion and help identify patients at high risk for ventricular arrhythmias and sudden death.
Differential diagnosis
INVM should be differentiated from normal thick myocardial trabeculae (less than 3), apical hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic right ventricular dysplasia, endocardial elastic fiber hyperplasia, metastatic foci of cardiac tumors, and left ventricular thrombosis.
Treatment
The treatment of INVM focuses on its 3 main clinical manifestations: heart failure, arrhythmia and thromboembolism. Systolic or diastolic insufficiency requires conventional drug therapy. Heart transplantation is indicated for refractory heart failure. β-blocker carvedilol is beneficial in improving left ventricular function and neurohumoral disturbances. Because of the risk of ventricular arrhythmias and sudden cardiac death, patients should have an ambulatory electrocardiogram at least once a year to evaluate for atrial and ventricular arrhythmias. An automatic cardioverter-defibrillator (ICD) can be implanted in high-risk patients. Biventricular pacing is indicated for patients with heart failure with wide QRS intervals.
Another important aspect of INVM therapy is the prevention of thromboembolism. Some authors recommend that all patients should receive long-term prophylactic anticoagulation, regardless of whether thrombosis is detected.
Prognosis
Approximately half of patients with INVM die or receive a heart transplant during follow-up. Compared to adult patients, children are at a lower risk of body circulation embolism, ventricular arrhythmias, and death, although severe cases are not uncommon. Higher left ventricular diastolic diameter, New York Heart Association cardiac function class (NYHA) III-IV, permanent or persistent atrial fibrillation, and bundle branch block often suggest a poor prognosis and the need for early intervention such as an ICD or heart transplantation.
References
[1] Chin TK, Perloff JK, Williams RG, Jue K, Mohrmann R. Isolated noncompaction of the left ventricular myocardium. a study of eight cases. Circulation. 1990 ;82(2):507-13.
[2] Weiford BC, Subbarao VD, Mulhern KM. Noncompaction of the ventricular myocardium. Circulation. 2004;109(24):2965-71.
[3] Ma Pei Ran, Han Bo. Isolated ventricular myocardial densification insufficiency. In: Yang S.Y., ed. Pediatric Cardiology. 3rd edition. Beijing: People’s Health Publishing House, 2005, 419-420
[4] Wang Xiao Fang Han Ling Report of four cases of isolated ventricular myocardial densification insufficiency. Chinese Journal of Pediatrics. 2002;40:81-83