Noncom paction of ventricular myocardium (NVM) is a rare congenital myocardial disorder that is characterized by a failure of reticular myocardium densification during early embryonic development, resulting in the persistence of trabecular myocardium, characterized by numerous protruding trabeculae within the ventricles, deep inter-trabecular fossa, and reduced ventricular systolic and diastolic function. This is characterized by many protruding trabeculae in the ventricle, deep inter-trabecular fossa, and reduced ventricular systolic and diastolic function.
In recent years, with the widespread use of echocardiography and cardiac magnetic resonance imaging, this disease has been increasingly detected and has attracted attention. This article reviews the nomenclature, etiology and clinical aspects of NVM as follows.
1. Nomenclature and classification
This disease was once called myocardial sinus gap persistence because of the presence of sinus gaps in the myocardium on ventriculography. In 1990, chin et al. confirmed that such patients have a restricted morphogenesis of the endocardium, resulting in a sponge-like appearance of the developing myocardial trabeculae. In 1990, chin et al. demonstrated that these patients had failed to densify the developing myocardial trabeculae due to restricted endocardial morphogenesis.
The definition of “persistent myocardial sinusoidal gap” is considered inappropriate because histologically the trabecular surface of the lesion is covered with a layer of endothelial cells and the deep trabecular fossa is not a myocardial sinusoidal gap; in addition, although a very large number of myocardial trabeculae in NVM have a spongy appearance, not all myocardium with many myocardial trabeculae is “spongy”. In addition, although the myocardium of NVM has a very spongy appearance, not all myocardium with many myocardial trabeculae is “spongy myocardium”, and obviously this name is also inappropriate; it is more appropriate to call it myocardial densification insufficiency, which basically expresses the meaning of the mechanism of occurrence and the general morphology of the disease.
In the 1995 WHO report on the definition and classification of cardiomyopathies, these cases were classified as unclassified cardiomyopathies, and in the new definition and classification criteria of the American College of Cardiology for cardiomyopathies in March 2006, NVM was classified as hereditary cardiomyopathy. NVM can be divided into two categories based on the presence or absence of complications: isolated ventricular myocardial insufficiency without cardiac malformations (INVM) and myocardial densification insufficiency with other congenital heart diseases (e.g., atrial or ventricular septal defects and other complex cyanotic congenital heart diseases, heart valve malformations, etc.).
Depending on the location of the densification insufficiency, NVM can be divided into left ventricular, right ventricular, and biventricular types, with the left ventricular type being the most common.
2.Onset
The disease may be disseminated or may occur in family clusters. The incidence of NVM can be seen at any age and there is no difference between the sexes, but some literature suggests that it is more common in men. 2000 was the first report of myocardial densification insufficiency in China, and by 2005, more than 80 cases and 4 families had been reported.
3. Etiology and pathogenesis
The etiology and pathogenesis of NVM are unknown. Bleyl et al. first reported a family of 6 males with concomitant myocardial densification insufficiency with an associated gene G4.5 located at Xq28; subsequently, it was found that adult myocardial densification insufficiency is mostly autosomal dominant, with an associated gene located at fragment 11p15. The current study showed that NVM is associated with the DTNA gene at 18 q12.1 to q12.2, csx at 5q35.1, the human 20pB homologous sequence of the mouse FKBP12 gene, and a gene deletion at Lq43.
During the first month of normal human embryonic development, myocardial tissue consists of “sponge-like” loose reticular myofibers that form trabeculae and deep trabecular crypts, and the blood supply to the trabeculae comes from the trabecular gap in direct communication with the ventricular chambers. During the second month of embryonic development, the loose trabecular network gradually densifies, the deep trabecular gaps are converted into capillaries, and the developing coronary circulation anastomoses with the formed venous network, and blood supply remodeling occurs.
The process of ventricular muscle densification gradually proceeds from the epicardial side to the endocardial side and from the base to the apex of the heart. In case of developmental defects, morphogenesis of endocardial myocardium is blocked, the intermyocardial sinusoidal gap is not closed, densification of reticular myocardial fibers fails, and histologically spongy pathological changes of myocardial trabeculae separated from inter-trabecular crypt foci are formed. The presence of trabecularization leads to intramural perfusion derangement and myocardial involvement resulting in abnormal compliance leading to decreased diastolic and systolic function of the ventricular muscle.
4. Pathology and physiology
NVM lesions most often involve the left ventricle, but may also involve the right ventricle, and rarely only the right ventricle. The lesions are mostly located in the apical part and lateral wall of the ventricle, while the septum and the bottom of the heart are rarely involved. The outer layer is a thin dysplastic myocardium composed of densified myocardium; the inner layer is an endocardial band of hypertrophic trabeculae, thicker and composed of non-densified myocardium, which is characterized by numerous trabeculae protruding from the ventricular cavity and deep trabecular fossa, which reaches 1/3 of the outer ventricular wall and communicates with the ventricular cavity.
With or without enlargement of the ventricular cavity, the coronary arteries remain normally distributed and the surface of the heart is generally free of abnormalities. However, NVM has been reported to be combined with atrial septal and ventricular septal tumors, and even left ventricular wall tumors. Pathological histological examination of NVM using endomyocardial biopsy, biopsy or autopsy was found to be characterized by varying degrees of subendocardial fibrosis, fibroelastic tissue degeneration, myocardial fibrosis, myocardial structural destruction, myocardial hypertrophy, myocardial scarring and inflammatory phenomena.
Heart failure, arrhythmias and thrombosis are the main pathophysiologic features of NVM. Heart failure tends to have a slowly progressive course, and diastolic dysfunction is due to increased ventricular end-diastolic pressure caused by increased active relaxation impairment and ventricular wall stiffness due to coarse myocardial trabeculae and decreased compliance. The main cause of systolic dysfunction is chronic myocardial ischemia. The increased demand for blood from multiple abnormal protruding myocardial trabeculae and the mismatch of blood supply to the heart are important causes of myocardial ischemia.
The majority of arrhythmias are fatal ventricular arrhythmias, but atrial arrhythmias can also occur, and rarely conduction block can occur. The mechanism of the arrhythmia is not well understood and may be related to irregular branching and connections at the base of the muscle bundle, increased ventricular wall tension during isovolumic contractions, resulting in tissue damage and delayed excitation. There are reports of cardiac conduction bundle Purkinje fibers found in the pseudotendinous-like mast muscle trabeculae of this disease, which may be one of the anatomical bases of the arrhythmia.
Cardiac thrombosis and thromboembolic events are due to slow blood flow in the deep crypt of myocardial trabeculae and concomitant atrial fibrillation that predisposes to the formation of intramural thrombi and the dislodgement of emboli.
5.Clinical manifestations
The onset of NVM is insidious and the clinical manifestations are nonspecific. It can occur in both children and adults, and the age of onset varies widely, from birth to middle age, or it can be asymptomatic for life. The onset of the disease is usually in middle age, with progressive heart failure, arrhythmias and thromboembolism as the main manifestations. Common signs and symptoms include palpitations, chest tightness, dyspnea, dizziness, syncope, edema, chest pain, heart murmur and embolism-induced slurred speech, impaired limb movement or gangrene.
It may or may not be associated with other congenital cardiac malformations. A few cases may be associated with facial deformities, such as prominent forehead, low ears, and high jaw arch. Some cases may have myasthenia gravis and myospasm.
6. Ancillary tests
6.1 Echocardiography
Echocardiography is of great value in the diagnosis of NVM, showing not only the abnormal features of the myocardial structure of NVM, but also the structure and function of the myocardium in the non-trabecularized region, and also diagnosing coexisting cardiac malformations at the same time. The features are: a large number of prominent myocardial trabeculae and deep inter-trabecular fossa can be detected in the ventricular cavity, and the protruding myocardial trabeculae show more regular serrated changes, mainly in the apical and anterolateral walls of the left ventricle, which can spread to the middle part of the ventricular wall, but generally do not involve the basal part of the ventricular wall.
In cross-section, the internal contour of the ventricle is seen to be foveated. The outer layer of the ventricular wall is significantly thinner and more hypoechoic, while the inner layer of strongly echogenic myocardium is sparse and thickened, with abundant trabecular tissue. Color Doppler showed blood filling in the trabecular space, reduced flow velocity and communication with the ventricular cavity. The affected ventricles are enlarged to varying degrees and the wall motion is reduced. Ultrasonography can clearly show the boundaries of the cardiac chambers and endocardium, and the contrast agent can completely fill the trabecular crypt, which is helpful to improve the accuracy of NVM diagnosis.
6.2 Magnetic resonance examination
Magnetic resonance examination shows myocardial thickening and stratification, and the maximum ratio of non-dense myocardium to dense myocardium at end-diastole is greater than 2.0. Double inversion recovery fast spin-echo sequences of two-chamber and four-chamber hearts can clearly show multiple thick, staggered, reticular or spongy trabecular structures in the heart chambers, which show a flow-space signal or inhomogeneous signal. Triple inversion spin-echo sequences can show blood flow in the trabecular crypt. It may also show reduced motion of the ventricular wall in the lesion area.
6.3 Ultrahigh-speed computed tomography
The lesioned myocardium can be shown as two separate layers with different densities, i.e., a thinning outer layer of dense myocardium and a thickened inner layer of non-dense myocardium. Enhanced imaging shows contrast filling between the crypt of myocardial trabeculae.
6.4 Thallium myocardial imaging
Demonstrates hypoperfusion changes in the relevant region.
6.5 Cardiac catheterization
It showed normal end-diastolic volume and increased pressure in the left ventricle, hypokinetic left ventricular function, and no left ventricular outflow tract obstruction; left ventriculography showed indistinct and feathery endocardial borders in the diastolic phase of the ventricle, with contrast remaining in the crypt in the systolic phase; endomyocardial biopsy showed thickened fibrous tissue in the endocardium of the lesion area, with thick and short myocardial fibers, surrounded by a large number of collagen fibers, with inflammatory cell infiltration visible between them.
6.6 Electrocardiographic examination
88%-94% of patients with NVM have ECG abnormalities, but they are not specific. The common ones include various types of arrhythmias, bundle branch conduction block, abnormal Q waves, ST-T changes, and ventricular hypertrophy.
7.Diagnosis and differential diagnosis
The clinical manifestations and electrocardiogram of NVM are not specific, while echocardiography is a reliable method to diagnose this disease and can confirm the diagnosis. Echocardiographic diagnostic criteria: (1) the myocardium is clearly divided into two layers, namely the thin and dense outer layer of the heart and the thick and lax inner layer of the heart; (2) the ratio of the thickness of the inner and outer layers of the heart is >2.0 (children >1.4); (3) color Doppler shows that the blood in the systolic heart cavity enters directly into the deep trabecular space during systole. Magnetic resonance, ultra-high-speed electronic computed tomography and left ventriculography are also of great value for diagnosis.
The diagnosis of NVM should be differentiated from the following diseases.
(1) Hypertrophic cardiomyopathy: Although hypertrophic cardiomyopathy can have thick myocardial trabeculae, there is no deep septa and asymmetric hypertrophy of the left ventricular wall and septum can be seen, so it can be differentiated from NVM;
(2) dilated cardiomyopathy: dilated cardiomyopathy can also have more protruding myocardial trabeculae, but the number is less than that of NVM, and there is enlargement of the heart chambers and uniform thinning of the ventricular wall, which can be distinguished from NVM;
(3) Ischemic cardiomyopathy: NVM can have abnormal Q waves and even form ventricular wall tumors, so it is often misdiagnosed as ischemic cardiomyopathy, but there is no history of typical angina pectoris or myocardial infarction, and coronary angiography is normal, which is helpful for differentiation.
8.Treatment and prognosis
There is no effective treatment for NVM. Currently, the main goal is to prevent and treat various complications such as heart failure, arrhythmias and thromboembolism. Diuretics, beta-blockers and angiotensin-converting enzyme inhibitors can be used to combat heart failure; coenzyme Q10, vitamin B and trimetazidine can also be applied to improve myocardial energy metabolism; heart transplantation is required for severe and intractable heart failure.
Anti-arrhythmic drugs can be selected for the type of arrhythmia; amiodarone is a safe and effective anti-ventricular tachyarrhythmia drug; recurrent ventricular tachycardia can be installed with a buried cardioverter-defibrillator. Aspirin or warfarin can be used as antithrombotic therapy to prevent thromboembolic events.
The prognosis of NVM is poor. in a group of 17 patients aged 18 to 71 years with myocardial densification insufficiency reported by Mayo Hospital, during a 6-year follow-up, 8 died and 2 underwent heart transplantation. oechslin et al. followed 34 symptomatic adult patients with NVM for (44±39) months, 18 were hospitalized for heart failure, 12 died (6 each of death from heart failure and sudden death), and 14 Ventricular arrhythmias were observed in 14 cases and thromboembolic events occurred in 8 cases.