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

Abstract

Aims: To characterize the phenotype, clinical outcomes and rate of disease progression in patients with early-stage non-ischaemic cardiomyopathy (early-NICM).

Methods and results: We conducted a prospective observational cohort study of patients with early-NICM assessed by late gadolinium enhancement cardiovascular magnetic resonance (CMR). Cases were classified into the following subgroups: isolated left ventricular dilatation (early-NICM H-/D+), non-dilated left ventricular cardiomyopathy (early-NICM H+/D-), or early dilated cardiomyopathy (early-NICM H+/D+). Clinical follow-up for major adverse cardiovascular events (MACE) included non-fatal life-threatening arrhythmia, unplanned cardiovascular hospitalization or cardiovascular death. A subset of patients (n = 119) underwent a second CMR to assess changes in cardiac structure and function. Of 254 patients with early-NICM (median age 46 years [interquartile range 36-58], 94 [37%] women, median left ventricular ejection fraction [LVEF] 55% [52-59]), myocardial fibrosis was present in 65 (26%). There was no difference in the prevalence of fibrosis between 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. Non-sustained ventricular tachycardia (hazard ratio [HR] 5.1, 95% confidence interval [CI] 2.36-11.00, p < 0.001), myocardial fibrosis (HR 3.77, 95% CI 1.73-8.20, 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 dilated cardiomyopathy with LVEF <50% over a median of 16 (11-34) months.

Conclusion: Early-NICM is not benign. Fibrosis develops early in the phenotypic course. In-depth characterization enhances risk stratification and might aid clinical management.

Keywords: Fibrosis; Non-ischaemic cardiomyopathy; Risk stratification.

Figure 1

Late gadolinium enhancement (LGE) position and pattern in patients with early‐stage non‐ischaemic cardiomyopathy (NICM). American Heart Association 17‐segment model is used to represent LGE position. Three myocardial layers (subepicardial, mid‐wall and subendocardial) are used to represent late gadolinium pattern. In patients with isolated left ventricular dilatation, fibrosis was mostly identified at the basal level_, whereas fibrosis was more frequently found at basal and mid‐level in non‐dilated left ventricular cardiomyopathy and early dilated cardiomyopathy. The proportion of patients with fibrosis in each myocardial layer was similar between subgroups. Early‐NICM H−/D+, isolated left ventricular dilatation; early‐NICM H+/D−, non‐dilated left ventricular cardiomyopathy; early‐NICM H+/D+, early dilated cardiomyopathy.

Figure 2

Cumulative incidence of major adverse cardiovascular events (MACE) stratified by (A) early non‐ischaemic cardiomyopathy (NICM) subgroups; and (B) early‐NICM versus dilated cardiomyopathy (DCM) with left ventricular ejection fraction <50%. Results are suggestive of a higher cumulative incidence of MACE in patients with early‐DCM (early‐NICM H+/D+) compared to patients with non‐dilated left ventricular cardiomyopathy (early‐NICM H+/D−) or isolated left ventricular dilatation (Early‐NICM H−/D+) (A). Patients with DCM with left ventricular ejection fraction <50% had a higher cumulative incidence of MACE than patients with early NICM (B). Early‐NICM H−/D+, isolated left ventricular dilatation; early‐NICM H+/D−, non‐dilated left ventricular cardiomyopathy; early‐NICM H+/D+, early dilated cardiomyopathy.