Global longitudinal strain on cardiac magnetic resonance predicts malignant ventricular arrhythmias and heart failure outcomes in phospholamban p.(Arg14del) cardiomyopathy
K M Reimert, B Mahmoud, A B P Noordman, M Y C Van Der Heide, A A M Wilde, L M G Meems, M G P Cox, A H Maass, N H J Prakken, B WestenbrinkAbstract
Background
The pathogenic PLN p.(Arg14del) variant is associated with an arrhythmogenic cardiomyopathy characterized by a high burden of malignant ventricular arrhythmias (MVA) that often precede overt structural remodeling. Risk stratification remains challenging, as conventional markers such as LVEF may remain preserved.
Purpose
We aimed to evaluate whether CMR-derived myocardial strain provides independent prognostic value for MVA and heart failure (HF) events in PLN p.(Arg14del) carriers.
Methods
We retrospectively included 279 PLN p.(Arg14del) carriers from two academic centers. All patients underwent CMR; feature-tracking was used to assess global longitudinal (GLS), radial, and circumferential strain. Time-normalized strain–time curves were constructed to evaluate temporal behavior. Multivariable Cox regression, adjusting for age, LVEF, epicardial adipose tissue (EAT) volume, BMI, ventricular ectopy, and microvoltages, was used to assess the association between strain and MVA (sustained VT, VF, cardiac arrest, or appropriate ICD shock) or a composite HF outcome (HF hospitalization and all-cause mortality).
Results
A total of 279 patients were included (42±16 years, 55.9% female, mean LVEF 52.9±10.1%). Over a median follow-up of 65 months (IQR 38–94), 34 (12.1%) patients developed an MVA and 24 (8.6%) reached the HF composite endpoint. Time-normalized strain–time curves demonstrated significantly reduced longitudinal strain throughout the cardiac cycle in patients with clinical events compared with those without (Figure 1A). GLS was a strong independent predictor of MVA (Figure 1B) and HF events (HR 1.56 [95% CI 1.00–2.44], p=0.049). Radial and circumferential strains were not associated with outcomes. Impaired GLS was independently associated with male sex, higher age, lower LVEF, and higher EAT volume (all p < 0.001).
Conclusion(s)
In PLN p.(Arg14del) carriers, impaired global longitudinal strain (GLS) is a strong, independent predictor of MVA and HF events. CMR-derived GLS identifies high-risk patients beyond conventional measures and may improve risk stratification in the early stages of the disease.For image description, please refer to the figure legend and surrounding text.