The malignant Arg 719 Trp mutation in hypertrophic cardiomyopathy was associated with a greater left ventricular mass index than the benign Val 606 Met mutation (148.0 vs 111.7 g/m2; p=0.023).
Observational (n=56)
Does the prognostic significance of specific β-MyHC mutations correlate with their hypertrophic expressivity in patients with hypertrophic cardiomyopathy?
The prognostic severity of specific β-MyHC mutations in hypertrophic cardiomyopathy is directly reflective of the extent of left ventricular hypertrophy they produce.
Absolute Event Rate: 148% vs 111.7%
p-value: p=0.023
Background Genotype-phenotype correlation studies consistently have shown that mutations are prognosticators in patients with hypertrophic cardiomyopathy (HCM). While Arginine (Arg) 719 Tryptophan (Trp) mutation in the β-myosin heavy chain (MyHC) gene is associated with a high incidence of sudden cardiac death (SCD), the Valine (Val) 606 Methionine (Met) mutation in the same gene is associated with a near normal life expectancy. It is unknown whether the prognostic significance of mutations is reflective or independent of their hypertrophic expressivity. We determined the indices of left ventricular hypertrophy (LVH) in patients with β-MyHC mutations associated with high, moderate, and low incidence of SCD. Methods Mutations were identified by chemical cleav-age (Val 606 Met and Glu 930 Lys) or polymerase chain reac-tion (PCR) and Mspl restriction mapping (Arg 719 Gln). Left ventricular mass was determined using 2-D echocardio-grams, and was indexed (LVMI) for body surface area. The extent of LVH was determined using a semiquantitative point score method that takes into account the extent of involvement of the septum, apex, and lateral wall of the left ventricle. Results The Arg 719 Trp, Glu 930 Lys, and Val 606 Met muta-tions were associated with high (14/29, 48%), moderate (3/16, 19%), and low (1/11, 9%) risk of premature death, respec-tively. Concordant with the incidence of premature death, the LVMI was the greatest (148.0 ± 37 g/m 2 ) in patients with the Arg 719 Trp mutation, the smallest (111.7 ± 19 g/m 2 ) in patients with the Val 606 Met mutation, and in between (127.1 ±15 g/m 2 ) in patients with the Glu 930 Lys mutation (p = 0.023). Similarly, the LVH score was also greater in patients with the Arg 719 Trp mutation than in those with the Val 606 Met mutation (5.92 ± 2.3 vs 3.2 ± 1.5, respectively, p = 0.015). A trend toward a greater septal thickness was also present in patients with the Arg 719 Trp compared to the Val 606 Met muta-tions (20.7 ± 6.8 mm vs 16.2 ± 2.6 mm, p = 0.077). Conclusion Hypertrophic cardiomyopathy patients with the malignant Arg 719 Trp mutation have more extensive hypertrophy than those with the benign Leu 606 Val mutation. This finding suggests that the prognostic significance of β-MyHC mutations is reflective of their hypertrophic expres-sivity.
Abchee et al. (Tue,) conducted a observational in Hypertrophic cardiomyopathy (n=56). Arg 719 Trp β-MyHC mutation vs. Val 606 Met β-MyHC mutation was evaluated on Left ventricular mass index (LVMI) (p=0.023). The malignant Arg 719 Trp mutation in hypertrophic cardiomyopathy was associated with a greater left ventricular mass index than the benign Val 606 Met mutation (148.0 vs 111.7 g/m2; p=0.023).