Abstract 4138491: Association of histologic findings with long-term outcomes in symptomatic obstructive hypertrophic cardiomyopathy patients undergoing surgical myectomy

Background: In hypertrophic cardiomyopathy (HCM), histologic findings like myocyte hypertrophy&disarray, interstitial fibrosis (IF)&small intramural coronary arteriole dysplasia (SICAD) account for the left ventricular hypertrophy, diastolic dysfunction, arrhythmogenicity&microvascular ischemia. Objectives: To evaluate the association between histology&outcomes in obstructive HCM (oHCM) patients undergoing surgical myectomy (SM). Methods: This was an observational study of 1722 symptomatic oHCM patients (mean age 56±14 years, 948 [55%] men) who underwent SM at a tertiary care center between 2005-18. Baseline clinical data was collected. The SM specimen was analyzed for presence&severity of a) myocyte hypertrophy b) myocyte disarray c) IF&d) SICAD. Histologic findings were graded as 0-3 (none, mild, moderate,&severe)&a score from 0-12 was calculated. Primary endpoint was a composite of death, appropriate defibrillator discharge or cardiac transplantation during follow-up. Results: 896 (52%) were in New York Heart Association (NYHA) class III/IV, 457 (21%) had exertional syncope, 727 (42%) had ≥1 sudden death risk factor&409 (24%) had atrial fibrillation (AF). Moderate&severe histologic findings were distributed as follows: myocyte hypertrophy (1341 [78%]), disarray (237 [14%]), IF (448 [26%])&SICAD (258 [15%]). The mean total histologic score was 5.1±1.4. At 5.1±5.2 years, there were 352 (20%) primary events (317 [18%] deaths). On spline analysis (Figure 1A), a total histology score of ≥ 6 was associated with primary events. On Kaplan-Meier analysis (Figure 1B), patients with a histology score ≥ 6 had greater events vs. those with a score <6 (147/598 [25%] vs. 205/1124 [18%], log-rank p-value 0.002). On multivariable Cox analysis, age (for 10-year increase, Hazard ratio or HR 1.49 [95% confidence interval or CI 1.35-1.65], p<0.001), NYHA Class III/IV (HR 1.58 [95% CI -1.25-2.01], p<0.001), AF (HR 1.65 [95% CI 1.30-2.10], p<0.001)&histology score ≥6 (HR 1.24 [95% CI 1.03-1.54], p=0.03) were independently associated with higher primary events. Conclusions: In symptomatic oHCM patients undergoing SM, a higher histologic score was independently associated with long-term outcomes.