MYH7 Mutations in Restrictive Cardiomyopathy

Figures

• 

  Figure 1. Genetic Test Results of the RCM Cohort (A) Oncoplot of patients carrying P/LP variants. (B) MYH7 is the most mutated gene, and its visualization on the transcript. MYH7 = myosin heavy chain 7; P/LP = pathogenic/likely pathogenic; RCM = restrictive cardiomyopathy.

• 

  Figure 2. Kaplan-Meier Survival Curves Comparing the Clinical Time of RCM Patients in Variant-Positive vs Variant-Negative Groups (A to C) Comparing variant-positive (red) and variant-negative (blue) patients by age of onset, diagnosis, and HTx. (D to F) Comparing variant-positive (red) and variant-negative (blue) patients for onset to HTx, diagnosis to HTx, and onset to diagnosis. Shaded areas represent the 95% CIs, and log-rank P values show significant differences. HTx = heart transplantation; RCM = restrictive cardiomyopathy.

• 

  Figure 3. Kaplan-Meier Survival Curves and Cox Regression Model Comparing the Clinical Time Intervals of RCM Patients Based on Genetic Variant Status Kaplan-Meier survival curves comparing patients (A) with no variants (blue), MYH7 variants (red), and other variants (green) for survival from diagnosis to heart transplantation (HTx, left) and from disease onset to ICD implantation (right). (B) Patients with no variants (blue), sarcomeric variants (red), and other variants (green) for survival from diagnosis to HTx (left) and from disease onset to ICD implantation (right). (C) Patients with no variants (dark blue), MYH7 variants (red), sarcomeric variants excluding MYH7 (green), and other variants (light blue) for survival from diagnosis to HTx (left) and from disease onset to ICD implantation (right). The number of patients at risk at various time points is noted below. Shaded areas represent the 95% CIs, and log-rank P values show significant differences. (D) HRs for heart transplantation risk associated with different mutations in RCM patients, as determined by a Cox regression model. ICD = implantable cardioverter-defibrillator; other abbreviations as in Figures 1 and 2.

• 

  Figure 4. The Natural History of 44 RCM Patients From Initial Symptoms to Heart Transplantation in Each Group HTx = Heart Transplantation; RCM = restrictive cardiomyopathy.

• 

  Figure 5. Comparative Histopathology of RCM Affected by MYH7 Mutation vs Other Mutations and Nonmutation Cases (A) Masson's trichrome staining map of 6 site pathology of transplant patients. RCM myocardium with MYH7 mutation, highlighting extensive blue-stained collagen indicating significant fibrotic tissue and accumulation of lipofuscin. The distribution of myocardium (red), fibrosis (yellow), and adipose (green) are correspondingly shown. (B-D) Qualitative pathological analysis was used to quantify the degree of myocardium proportions, fibrosis, and adipose invasion at different sites (LV, IVS, and RV) in MYH7 mutation, metabolic-related mutations, other mutations, and nonmutation transplant patients. ∗P < 0.05; ∗∗P < 0.01. IVS = interventricular septum; LV = left ventricle; RV = right ventricle; other abbreviations as in Figure 1.

• 

  Central Illustration. MYH7 Mutations in Restrictive Cardiomyopathy (A) Study workflow for the RCM cohort. (B) Genetic variant distribution and heart transplantation outcomes, with the distribution of genetic variants identified in the RCM cohort, including MYH7 mutations, structural variants, metabolism-related variants, other sarcomeric variants, and variants in other categories (left), and the Kaplan-Meier survival analysis compares heart transplantation-free survival among patients with MYH7 mutations, other variants, and variant-negative cases (right). (C) Pathological features of MYH7-positive and variant-negative patients. Abbreviations as in Figure 1.