26 Phenotype, outcomes and natural history of early-stage non-ischaemic cardiomyopathy

Introduction With expansion of family screening, genetic testing and advanced cardiovascular imaging, more patients are being diagnosed with early-stage non-ischaemic cardiomyopathy (early-NICM), often before symptom-onset. Observational studies of such patients are lacking. We sought to characterise early-NICM phenotype, evaluate risk of adverse outcomes and assess the rate of disease progression. Materials and Methods We conducted a prospective observational cohort study of patients with early-NICM assessed by LGE-CMR. Cases were classified based on presence/absence of LV dilatation and reduced LVEF into subgroups: isolated LV dilation (early-NICM H-/D+) in cases with LV dilatation without hypokinesia; non-dilated LV cardiomyopathy (early-NICM H+/D-) in cases with hypokinesia without dilatation; early dilated cardiomyopathy (early-NICM H+/D+) in cases with LV dilatation and mild hypokinesia. Follow-up for major adverse cardiovascular events (MACE) included life-threatening arrhythmia, unplanned cardiovascular hospitalisation or cardiovascular death. A subset of patients (n=119) underwent a second CMR to assess changes in cardiac structure and function. Results Of 254 patients with early-NICM (median age 46 years [IQR 36–58], 94 [37%] women, median LVEF 55% [52–59]), myocardial fibrosis was present in 65 (26%). There was no difference in the prevalence of fibrosis among subgroups (p=0.90), however fibrosis mass was lowest in early-NICM H-/D+, higher in early-NICM H+/D- and highest in early-NICM H+/D+ (p=0.03). Over a median follow-up of 7.9 (5.5–10.0) years, 28 patients (11%) experienced MACE. Myocardial fibrosis (HR 3.77, 95%CI 1.73–8.20, p<0.001), non-sustained VT (HR 5.10, 95%CI 2.36–11.00, p<0.001) and diabetes mellitus (HR 5.12, 95%CI 1.73–15.18, p=0.003) were associated with MACE in a multivariable model. Only 8% of patients progressed from early-NICM to DCM with LVEF<50% over a median of 16 (11–34) months. Discussion Myocardial fibrosis deposition occurs early in the phenotypic course of NICM, often preceding obvious adverse cardiac remodelling or symptom-onset. The observation of a gradient in fibrosis mass across early-NICM subgroups suggests it may be integral to disease progression. The finding that 11% of patients with early-NICM experienced MACE over long-term follow-up highlights the importance of risk stratification and surveillance, despite the low rate of early phenotypic progression. Conclusion Early-NICM is not benign. Fibrosis is an early feature of disease. In-depth characterisation enhances risk stratification and might aid clinical management. Acknowledgements We thank the Royal Brompton and Harefield Cardiovascular Research Centre nurses and support staff.