Deep basal inferoseptal crypts occur more commonly in patients with hypertrophic cardiomyopathy due to disease-causing myofilament mutations

This study, which was performed in a cohort of 300 consecutive individually genotyped and unrelated patients with hypertrophic cardiomyopathy (HCM) and the full spectrum of morphologic manifestations from genotype-positive and phenotype-negative HCM to extreme hypertrophy, demonstrates that deep basal inferoseptal crypts occur significantly more frequently in patients with disease-causing mutations than in those without disease-causing mutations.

Purpose: To determine the relationship between deep basal inferoseptal crypts and disease-causing gene mutations in hypertrophic cardiomyopathy (HCM).

Materials and Methods: Institutional research and ethics board approval was obtained for this retrospective study, and the requirement to obtain informed consent was waived. Two readers, who were blinded to genetic status, independently assessed cardiac magnetic resonance (MR) images obtained in 300 consecutive unrelated genetically tested patients with HCM. Readers documented the morphologic phenotype, the presence of deep basal inferoseptal crypts, and the imaging plane in which crypts were first convincingly visualized. The Student t test, the Fisher exact test, and multivariate logistic regression were used for comparisons and to evaluate the relationship between these crypts and the detection of disease-causing mutations.

Results: The frequency of deep basal inferoseptal crypts was significantly higher in patients with disease-causing mutations than in those without disease-causing mutations (36% and 4%, respectively; P < .001). The presence of crypts was a stronger predictor of disease-causing mutations than was reverse septal curvature (P = .025). Patients with these crypts had a higher likelihood of having disease-causing mutations than non–disease-causing mutations (P < .001). Thirty-one of the 34 patients with both deep basal inferoseptal crypts and reverse septal curvature (91%) had disease-causing mutations (sensitivity, 26%; specificity, 98%). The presence of deep basal inferoseptal crypts (odds ratio: 6.64; 95% confidence interval: 2.631, 16.755; P < .001) and reverse septal curvature (odds ratio: 4.8; 95% confidence interval: 2.552, 9.083; P < .001) were predictive of disease-causing mutations. Both observers required additional imaging planes to identify approximately half of all crypts.

Conclusion: Deep basal inferoseptal crypts occur more commonly in patients with HCM with disease-causing mutations than in those with genotype-negative HCM.