Myocardial crypts in hypertrophic cardiomyopathy: the new gang in town.

Since the initial description of hypertrophic cardiomyopathy (HCM) over 50 years ago, the majority of our understanding of this complex and heterogeneous genetic heart disease has been the result of insights gained through advances in cardiovascular imaging techniques. 5 In the pre-echocardiographic era, the haemodynamic laboratory provided the sole method of diagnosis for HCM by demonstrating a pressure gradient between the left ventricular cavity and the aorta. The introduction of echocardiographic imaging in the early 1970s led to a greatly expanded appreciation for the vast heterogeneity of phenotypic expression in this disease, including the first non-invasive demonstration of the characteristic asymmetric pattern of LV hypertrophy, as well as defining the non-obstructive form as an important subset of the HCM disease spectrum. More recently, advanced imaging techniques such as cardiovascular magnetic resonance (CMR) have emerged, ushering in a new era of cardiac imaging. 5 CMR provides three-dimensional tomographic images with high spatial resolution, with sharp contrast between the blood pool and the myocardium. These unique imaging strengths make it particularly well suited to characterize the diverse morphological expression of HCM. Indeed, CMR has now been applied to large cohorts of HCM patients resulting in a number of clinically relevant observations, further expanding our appreciation and understanding of HCM disease expression beyond traditional imaging modalities. – 7 CMR improves diagnosis of HCM, by detecting LV hypertrophy unrecognized (or not well seen) by echocardiography, particularly when confined to the anterolateral free wall (or apex). –5 Furthermore, in some HCM patients, the magnitude of wall thickening may be underestimated by echocardiography, which may have important management implications when massive LV hypertrophy is detected by CMR (wall thickness ≥30 mm is an independent risk factor for sudden death). Other HCM patient subgroups identified with CMR include those with thin-walled scarred LV apical aneurysms (which prior to CMR imaging in HCM remained largely undetected) and end-stage systolic dysfunction (EF , 50%), in whom identification may raise additional management options including implantable cardioverter defibrillators for primary prevention and anticoagulation for stroke prophylaxis. CMR has also broadened our understanding of HCM disease expression to now include hypertrophy of the right ventricle, and morphological abnormalities of the papillary muscles and the mitral valve. –7 Contrast-enhanced CMR with late gadolinium enhancement (LGE) has generated tremendous enthusiasm by providing the opportunity to identify the abnormal myocardial substrate of fibrosis, a potential novel marker of risk. Over the last two decades, the availability of genetic testing in routine clinical cardiovascular practice has resulted in the identification of HCM family members who carry a diseasecausing sarcomere mutation (and therefore at risk of developing phenotypic HCM) but who are without LV hypertrophy, i.e. genotype positive–phenotype negative (G+P2) patients. This led to the observation with echocardiography that abnormalities of myocardial function are present in G+P2 patients, and the emerging principle that even in the absence of increased LV wall thickness, these hearts may be abnormal. CMR has added to these insights by demonstrating that a number of additional morphological abnormalities may be present in G+P2 patients, including LGE (i.e. fibrosis) and elongated mitral valve leaflets. This sets the stage for the Brouwer et al. paper. In this investigation, the authors have characterized a unique structural abnormality consisting of narrow, deep blood-filled invaginations within the LV myocardium of predominantly G+P2 HCM patients, termed myocardial crypts (or clefts). Crypts were detected only by CMR in the majority (70%) of G+P2 patients and in a much smaller number (12%) of control patients with other forms of congenital heart disease. Based on these initial observations, a number of questions have arisen, including: (i) why only recently