Myocardial scar in end-stage hypertrophic cardiomyopathy: correlation with systolic function and prognostic significance
Authors: Ditaranto R , Shiwani H , Davies R H , Malcolmson J , Pierce I , Moschonas K , Schiavo M A , Lorenzini M , Lovato L , Biagini E , Lopes L R , Mohiddin S A , Moon J C 
Published: October 2024

Abstract

Background
Hypertrophic cardiomyopathy with systolic impairment, often referred to as end-stage HCM (ES-HCM), has a poor prognosis. Scar is a significant contributor but the patterns and prognostic significance are unknown.

Aim
To understand role of scar in ES-HCM and investigate potential predictors of outcome.

Methods
A retrospective 4 centre study of ES-HCM (LVEF≤55%) who had undergone CMR between 2006 and 2022 for unexplained LVH. Exclusion criteria were: scaring therapies (septal reduction), phenocopies (amyloidosis, storage) and dual pathologies (severe aortic valve disease, previous infarction). CMR followed standardized protocols. All images were core-lab analysed de-novo with scar quantified using the full width at half maximum technique for late gadolinium enhancement (LGE) quantification in grams (LGEm) and percentage of total LV mass (LGE%). Cox models used to identify risk factors for all-cause mortality.

Results
From 3810 HCM CMR scans, 128 were ES-HCM pts (3%), 25(20%) were excluded due to known infarction. 103 (male n=82, 81%; age 57yrs[IQR51–68]) formed the study cohort. Of the 54% genotyped, 62% carried a (likely)pathogenic sarcomere mutation: MYBPC3 (n=20), MYH7 (n=7), TNNT2 (n=4), TMP1 (n=2),ALPK3 (n=1). Heart morphology was: 38(37%) isolated basal septal hypertrophy, 30(29%) reverse septal curvature, 7(7%) mid-cavity LVH with apical aneurysm, 3(3%) apical HCM, 24%other. The median EF was 46%(IQR 39-50). In only one third (34%) the ventricle was dilated (LVEDd mean 97ml/m2 IQR 79-112). The RV was impaired in 19(18%). Median max wall thickness was 17mm(IQR15-20) and LVmass 74mg/Kg(IQR65-90).
Scar was present in 94(93%) and was typically extensive: median LGE% 23%(IQR 13-33), LGEm 31g(IQR 16-45) – although 7% had no scar. The LGE pattern was diffuse in 38%, patchy in 35%, ring-like in 9%, and infarct-like in 7% (all without coronary narrowing at invasive/non-invasive coronary artery assessment). LGE and cardiac function were effectively independent with low or no correlation between scar and LVEF% or global longitudinal strain (r2=0.015,p=0.227 or r2= 0.048,p=0.028 for LGE% and LGEm against LVEF; r2=0.059,p=0.021 or r2=0.196,p&lt;0.001 for LGE% and LGEm against GLS) with poor correlation also with indexed stroke volume.
During a 5 year (IQR 3-7) follow-up (516patient-years), 30 deaths occurred: mean age at death was 62(52-74). Using multivariate Cox regression analysis EF and demographics such as age were not predictive, but LGE% (HR 1.046, 95%IC 1.007-1.086, p=0.019 and GLS (HR 1.172, 95%IC 1.004-1.368, p=0.044) were independent all-cause mortality predictors (C-index 0.708; table).

Conclusion
Myocardial scar is almost always present in ES-HCM and is typically extensive – but with some unexpected features: 7% of patients have no LGE, dual pathology(infarction) is not rare, and ringlike LGE (ALVClike) may occur. LGE correlates poorly with any measure of LV impairment but is a strong predictor of mortality, as is GLS.