Long-Term Imaging Follow-Up of Siblings with MYH7-Associated Left Ventricular Noncompaction

Description of Clinical Presentation: Two male siblings, currently aged 22 and 19, were diagnosed with left ventricular noncompaction cardiomyopathy (LVNC), during infancy, through family screening following their father's diagnosis. Both remain asymptomatic, with no documented history of significant arrhythmias. Genetic testing confirmed that each carried the same heterozygous pathogenic MYH7 variant: c.602C >T (p.Ile201Thr).

Diagnostic Techniques and Their Most Important Findings: Serial cardiac magnetic resonance (CMR) imaging was performed using 1.5T scanners. Cine steady-state free precession sequences (SSFP) were used for structural and functional evaluation, and late gadolinium enhancement (LGE) imaging was performed 10–15 minutes post-contrast to assess for fibrosis. Quantitative measurements adhered to Society for Cardiovascular Magnetic Resonance guidelines, including left/right ventricular volumes, ejection fractions, myocardial mass, and non-compacted to compacted myocardium ratios (NC/C).

At baseline, the older sibling demonstrated preserved left ventricular (LV) function (LVEF 58%), a normal indexed LV end-diastolic volume (LVEDVi) (89 mL/m²) and marked hypertrabeculation (NC/C ratio >3.3), predominantly in the mid-apical lateral wall and apex. No intracardiac thrombus was identified, and there was no evidence of LGE. Over nearly a decade of follow-up, all CMR parameters remained stable.

In contrast, the younger sibling initially showed borderline LV function, with an LVEF of 50% and an LVEDVi of 84 mL/m². Milder trabeculation was noted, with an NC/C ratio of 2.6, primarily affecting the lateral wall at the mid-apical and apical levels. Serial CMR demonstrated progressive LV dilation, with the LVEDVi increasing to 113.7 mL/m², along with a gradual decline in LVEF to 40.8%. Trabeculation also extended into the right ventricle (RV) over time. The indexed RV end-diastolic volume (RVEDVi) was 90.1 mL/m², with preserved RV function. A small LGE focus was noted at the interventricular insertion point of the inferior RV wall, a finding generally considered non-specific and benign.

The 57-year-old father demonstrated similar CMR findings, including a dilated LV with an LVEDV index of 121mL/m², marked hypertrabeculation of the mid-apical lateral wall and apex (NC/C ratio of 4), moderately reduced LVEF of 41% and no evidence of LGE. He is currently treated with sacubitril-valsartan, bisoprolol, and dapagliflozin, and reports mild exertional symptoms.

Learning Points from this Case: Despite sharing the same pathogenic MYH7 variant, the siblings exhibited different phenotypic expressions over time. One remained stable with preserved cardiac structure and function, while the other progressed to a dilated cardiomyopathy phenotype with biventricular involvement. This case highlights the value of long-term serial CMR in familial LVNC for detecting subtle disease progression before clinical symptoms emerge.

Figure 1. Cardiac magnetic resonance imaging (CMR) of the older sibling at diagnosis of left ventricular noncompaction cardiomyopathy (LVNC). Cine steady-state free precession (SSFP) sequences in the four-chamber and short axis views (a., b. and c.) reveal prominent non-compacted myocardium predominantly in the mid-apical antero-latero-posterior wall, and late gadolinium enhancement (LGE) (d.) confirms the absence of myocardial fibrosis.
Figure 2. Cardiac magnetic resonance imaging (CMR) of the younger sibling at diagnosis of left ventricular noncompaction cardiomyopathy (LVNC). Cine steady-state free precession (SSFP) sequences in the four-chamber and short axis views (a., b. and c.) reveal prominent biventricular non-compacted myocardium. Late gadolinium enhancement (LGE) imaging (d.) demonstrates a small, non-specific focus at the right ventricular insertion point.