Review articleLeft ventricular hypertrabeculation/noncompaction
Section snippets
History
LVHT is a fairly long-known abnormality of the LV and was first described in 1932 in a newborn at autopsy who showed aortic atresia and coronary-ventricular fistulae.12 Intra vitam LVHT was diagnosed for the first time in a 3-month-old female infant with dextrocardia, ventricular septal defect, and subpulmonary stenosis.4 In this patient, the ventriculography visualized the spongelike appearance of the LV wall during diastole, with marked retention of the contrast material in the
Pathoanatomic findings
LVHT is most frequently described as an abnormal finding of the LV apex and its adjacent parts of the lateral and inferior wall. In only 4 cases, LVHT of the interventricular septum has been described.19, 29, 41, 74 We currently have no explanation for the observed regional uneven distribution of LVHT within the LV. Possibly, the regional nonuniformity of the LV wall might contribute to this uneven distribution of LVHT. From anatomic studies it is known that in normal human hearts the thickest
Pathohistologic findings
Pathohistologic findings of LVHT, obtained intra vitam by endocardial biopsy or postmortem are unspecific. Either they are reported as being normal11, 20, 50, 60, 66, 71 or as showing subendocardial fibrosis/fibroelastosis,6, 18, 22, 25, 29, 41, 42, 53, 55, 57, 63, 64, 74 myocardial fibrosis,11, 12, 29, 56 myocardial disorganization,19 myocardial hypertrophy and degeneration,50 scarring of the myocardium,68 or signs of inflammation.11 Electron microscopy had been performed only in a few cases
Diagnostic criteria
Because of the lack of commonly accepted pathoanatomic diagnostic criteria, different echocardiographic criteria for LVHT are currently used. One group defines LVHT as “numerous, excessively prominent trabeculations and deep intertrabecular recesses.”11 In our experience, this definition is not clear-cut as it does not give a number above which the phenomenon is abnormal. On the contrary, we suggest the anatomically confirmed definition of >3 trabeculations within 1 imaging plane, apically from
Sex and age distribution
Among the 223 published cases in human beings (C.S., unpublished data, 2002),3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76 72 (32%) were female, 147 (66%) were male, and in 4 (2%) sex was not indicated. Possible explanations for this uneven sex distribution
Prevalence
The prevalence of LVHT found in different echocardiographic studies differs from 0.05 to 0.24%/y.62, 69, 76 The differences between the prevalence figures most probably result from different echocardiographic skill and awareness of this abnormality and from the imaging quality of the echocardiographic machine. Echocardiographic machines, using second harmonic imaging, visualize much better the apical regions of the LV, including detection of trabeculations and recesses, which might have been
Association with other cardiac and extracardiac, particularly neuromuscular, disorders
The association with other cardiac and extracardiac abnormalities is listed in Table 1. Coronary angiography had been performed in 74 patients and showed coronary abnormalities in 7 patients, significant coronary arteriosclerosis in 2 patients, and was completely normal in 65 patients. Symptoms of heart failure were reported by 52% of the patients, and palpitations or syncope by 16%. The electrocardiogram finding was abnormal in 74% of the patients, and showed most frequently ST- and T-wave
Familial occurrence
Although there are no systematic investigations on the familial occurrence of LVHT, there are single reports that demonstrate LVHT to occur in multiple family members. Familial occurrence has been reported in siblings,6, 9, 22, 26, 32, 39, 50, 53, 67, 76 half-brothers,6 parents and children,43, 50, 62 and in parental consanguinity.26, 42, 50 Two patterns of familial occurrence have been described. Some families show apparent X-linked recessive inheritance.6, 21, 22, 43 However, other family
Association with genetic findings
In LVHT cases, several mutations have been described.15, 22, 32, 33, 34, 35, 43, 59 The mutations concern the G4.5 gene encoding a protein family called the taffazins, genes encoding dystrophin or α-dystrobrevin, genes for transcription factors limited for the most part to the heart and mitochondrial mutations. In other cases, however, studies have been performed that failed to find any mutations in the G4.5 gene.52 So far it appears that LVHT is a morphologic abnormality with genetic
Pathogenetic concepts
Several pathogenetic concepts have been proposed to explain the occurrence of LVHT. First, LVHT is hypothesized to represent persistence of embryonal sinusoids and results from an arrest in the compaction process of the myocardium.12 Although this hypothesis is substantiated by the morphologic similarity of LVHT with the human heart during the eighth to tenth embryonic week, up to now there is no confirmation for this pathogenetic hypothesis.2 Arguments in favor of the embryonal hypothesis are
Prognosis
The prognosis of patients with LVHT is assessed controversially. In earlier reports, LVHT was reported to be associated with a high mortality as a result of heart failure and sudden cardiac death.6, 44 In the meantime, many cases of LVHT have been published with a better prognosis.9, 70 The longest follow up of a patient with LVHT is 20 years. This patient had remained free of symptoms for more than 18 years and then developed heart failure, which responded well to therapy.61 These differences
Therapy
There is no specific therapy for LVHT. However, because LVHT is often associated with other cardiac, neurologic, and noncardiac nonneurologic abnormalities, specific therapy is indicated and effective in patients with LVHT. LVHT associated with heart failure is effectively treated by angiotensin-converting enzyme inhibitors, beta-blockers, and diuretics.47, 61, 70, 73 In addition, in end stages of heart failure, heart transplantation might be necessary, which has been performed in 12 patients
Conclusion
In conclusion: (1) LVHT has a higher prevalence than previously thought and the prevalence of LVHT seems to increase with the improvement of cardiac imaging; (2) because LVHT is most frequently diagnosed primarily by echocardiography, echocardiographers should be aware and trained to recognize this abnormality; (3) LVHT is frequently associated with other cardiac and extracardiac, particularly neuromuscular, disorders; (4) there are indications that the cause of LVHT is usually a genetic one
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