The development of the hypertrophic cardiomyopathy (HC) phenotype with left ventricular (LV) hypertrophy usually occurs in adolescence, and documentation of patients with later onset of wall thickening during adulthood is rare. We report 4 patients with asymptomatic, nonobstructive HC (3 women and 1 man) who were studied with serial cardiovascular magnetic resonance imaging or echocardiography. In these patients, LV wall thickening, confined to the apex and the contiguous distal portions of the ventricular septum and free wall, appeared in midlife and beyond. These patients were >40, >50, or >70 years old when the hypertrophy became evident. The maximum LV wall thickness was 14 to 25 mm (mean 18), with a “spade” deformity of the distal chamber, associated with a nondilated cavity and normal ejection fraction (65% to 80%), in the absence of mitral valve systolic anterior motion. In each patient, similar electrocardiographic patterns with similar diffuse and marked T-wave inversion (with or without increased precordial voltages) preceded the appearance of the HC phenotype on the imaging studies. In conclusion, the recognition that the onset of LV hypertrophy in HC can be delayed well into adulthood (and even to advanced age) has important implications regarding the clinical screening practices for families, and suggests the potential value of extending prospective serial imaging beyond adolescence in some relatives. Electrocardiographic repolarization abnormalities can predict the future development of apical LV hypertrophy in adults with HC.
Left ventricular (LV) hypertrophy represents the phenotype of hypertrophic cardiomyopathy (HC) and is the basis for the clinical diagnosis. However, LV hypertrophy is rarely evident at birth or in young children but characteristically develops during adolescence. Although the de novo appearance of the HC phenotype in adults has been inferred by cross-sectional genotype-phenotype studies, the documentation of such events in individual patients with serial imaging studies has been uncommon, particularly in midlife after 40 years of age.
Apical HC is a part of the broad clinical and morphologic spectrum of HC. It is characterized by segmental hypertrophy confined to the distal portion of the LV chamber. Therefore, additional reports of delayed-onset LV hypertrophy, such as those in patients with apical HC, contribute importantly to our understanding of the clinical profile and natural history of this heterogeneous disease.
Methods
The database of the Hypertrophic Cardiomyopathy Center, Minneapolis Heart Institute Foundation (Abbott Northwestern Hospital, Minneapolis, Minnesota) was accessed. A search was conducted specifically for adult patients with ≥2 echocardiograms or cardiovascular magnetic resonance (CMR) imaging studies ≥2 years apart and obtained after age 21, for whom the initial study findings were normal but LV hypertrophy was subsequently identified. Paired imaging studies showing the development of LV hypertrophy were obtained with CMR in 3 patients (patients 1, 2, and 4; Table 1 ) and with 2-dimensional echocardiography in 1 patient (patient 3).
| Pt. No. | Initial Evaluation | Most Recent Evaluation | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age (yr)/Gender | Year | NYHA FC | Maximum LV Thickness (mm) | LV Mass Index ⁎ (g/m 2 ) | LVED † (mm) | LA † (mm) | EF (%) | Age (yr) | Year | NYHA FC | Maximum LV Thickness (mm) | LV Mass Index ⁎ (g/m 2 ) | LVED † (mm) | LA † (mm) | EF (%) | |
| 1 | 41/Male | 2004 | 1 | 10 | 66 | 51 | 35 | 66 | 48 | 2011 | 1 | 14 | 70 | 50 | 32 | 66 |
| 2 | 46/Female | 2004 | 1 | 10 | 58 | 35 | 31 | 77 | 51 | 2011 | 1 | 15 | 58 | 30 | 39 | 81 |
| 3 | 51/Female ‡ | 1990 | 1 | 10 § | NA | 46 | 31 | 65 | 60 | 1998 | 1 | 25 | NA | 53 | 38 | 65 |
| 4 | 74/Female | 2002 | 1 | 7 | 67 | NA | NA | NA | 82 | 2010 | 1 | 19 | 71 | 42 | 48 | 80 |
⁎ Normal LV mass: women, 34–70 g/m 2 ; men, 47–78 g/m 2 .
† Measurements made with echocardiography; all others, measurements made with CMR imaging.
‡ Comparative assessment of LV morphology with echocardiography; other 3 patients studied with CMR imaging.
§ Investigated by echocardiography with detection of right atrial myxoma (resected surgically).
The imaging studies were performed with a 1.5 Tesla clinical CMR scanner (Sonata or Avanto, Siemens Medical, Erlangen, Germany). Cine true fast imaging with steady state precession sequences were accessed in the standard horizontal long axis, vertical long axis, and LV outflow tract (echo time/repetition time 1.5/3.0 ms, flip angle 60, contiguous slice thickness 10 mm, in-plane resolution 1.5 × 1.5 mm, temporal resolution 45 ms, and breath hold duration 14 to 17 heartbeats) were performed during breath hold at end-expiration.
A short-axis image stack was obtained parallel to the atrioventricular groove (covering the entire left ventricle) with wall thickness measurements made at end-diastole in all segments of the chamber. Late gadolinium enhancement images were acquired 10 to 15 minutes after intravenous administration of 0.2 mmol/kg gadolinium-diethylene triamine pentaacetic acid (Magnevist, Schering, Berlin, Germany), with breath-held segmented inversion-recovery sequences acquired in the same orientations as the cine images.
The two-dimensional echocardiographic studies were performed with commercially available instruments. The magnitude and pattern of LV hypertrophy was measured in all cross-sectional planes. The maximum LV wall thickness was defined as the greatest dimension evident at any site within the chamber. The left atrial and LV end-diastolic cavity dimensions were assessed using M-mode echocardiography in a standard fashion. The peak instantaneous outflow gradient was estimated with continuous wave Doppler under basal conditions.
Results
In the 4 study patients (3 women and 1 man), the HC phenotype was absent at the initial evaluation (at 41, 46, 51, and 74 years of age, respectively), with normal wall thickness in all segments of the left ventricle. Subsequently, LV wall thickening was first identified at age 48, 51, 60, and 82 years ( Figures 1 and 2 ). Therefore, the onset of LV hypertrophy occurred after 40 years of age in each patient, including after 50 years in 1, and after 70 years in 1 patient, as determined by the serial imaging studies.
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