Hypertrophic cardiomyopathy and left ventricular non-compaction: Distinct diseases or variant phenotypes of a single condition?

Abstract

Hypertrophic cardiomyopathy (HCM) is a genetically determined myocardial disease characterized by an increased thickness of the left ventricle (LV) wall that cannot be solely attributed to abnormal loading conditions. HCM may present with an intraventricular or LV outflow tract obstruction, diastolic dysfunction, myocardial fibrosis and/or ventricular arrhythmias. Differentiating HCM from other diseases associated with LV hypertrophy, such as hypertension, aortic stenosis, or LV non-compaction (LVNC), can at times be challenging. LVNC is defined by excessive LV trabeculation and deep recesses between trabeculae, often accompanied by increased LV myocardial mass. Previous studies indicate that the LVNC phenotype may be observed in up to 5% of the general population; however, in most cases, it is a benign finding with no impact on clinical outcomes. Nevertheless, LVNC can occasionally lead to LV systolic dysfunction, manifesting as a phenotype of dilated or non-dilated left ventricular cardiomyopathy, with an increased risk of thrombus formation and arterial embolism. In extreme cases, where LVNC is associated with a very thickened LV wall, it can even mimic HCM. There is growing evidence of an overlap between HCM and LVNC, including similar genetic mutations and clinical presentations. This raises the question of whether HCM and LVNC represent different phenotypes of the same disease or are, in fact, two distinct entities.

Keywords: Hypertrophic cardiomyopathy; Left ventricle hypertrabeculation; Left ventricle hypertrophy; Left ventricle non-compaction; Left ventricle obstruction.

Figure 1

Different morphological changes in hypertrophic cardiomyopathy. A: Different cardiomyopathy (CMP) phenotypes. Dilated cardiomyopathy: Dilated CMP with left ventricle (LV) enlargement and hypokinesia. Hypertrophic cardiomyopathy (HCM): With increased LV mass or thickness. Restrictive cardiomyopathy: Restrictive CMP with enlarged atria; B: Morphological changes in mitral apparatus in HCM. Increased number and mass of papillary muscle heads, their atypical location, and elongation of the mitral leaflets; C and E: Different types and localization of LV hypertrophy; D: Phenotypic continuum between normal LV mass and structure, LV hypertrabeculation with normal LV mass [fulfilled diagnostic criteria for LV non-compaction (LVNC)], and hypertrabeculation with increased LV mass (fulfilled diagnostic criteria for LVNC and HCM). DCM: Dilated cardiomyopathy; HCM: Hypertrophic cardiomyopathy; IVS: Intraventricular septum; LV: Left ventricle; LVH: Left ventricular hypertrophy; MV: Mitral valve; PM: Papillary muscle; RCM: Restrictive cardiomyopathy; SAM: Systolic anterior motion.

Figure 2

Images from transthoracic echocardiography and cardiac magnetic resonance imaging of a 58-year-old woman with coexistence of left ventricle hypertrophy and hypertrabeculation leading to intracavitary obstruction with heart failure symptoms, and left ventricle thrombus formation with subsequent transient ischemic attack. A: Pulse-wave Doppler from apical 4-chamber transthoracic echocardiography (TTE) view showing intracavitary obstruction at the level of the papillary muscles (maximal resting gradient of 76 mmHg); B: Left ventricle (LV) apical hypertrophy in apical 4-chamber view in TTE; C and D: LV hypertrabeculation in cardiac magnetic resonance short axis view and 4-chamber view (ratio of thickness of non-compacted to compacted layers 2.1: 13 mm and 6 mm); E and F: LV thrombus entering between the LV trabeculae and recesses in short axis view and 4-chamber view (blue arrow).