Septal Late Gadolinium Enhancement and Arrhythmic Risk in Genetic and Acquired Non-Ischaemic Cardiomyopathies

Background

In many genetic and acquired non-ischaemic cardiomyopathies (NICM) there have been frequent reports of involvement of the interventricular septum (IVS) by late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR). However, no studies have investigated the relationship between septal LGE and arrhythmias in different NICM subtypes.

Methods

This study enrolled 103 patients with septal LGE at baseline CMR and different NICM: hypertrophic (n=29) or lamin A/C gene (LMNA)-associated (n=23) cardiomyopathy, and acute (n=30) or previous (n=21) myocarditis. During follow-up, the occurrences of malignant ventricular arrhythmias (MVA) and major bradyarrhythmias (BA) were evaluated.

Results

At 4.9±0.7 years of follow-up, the occurrence of MVA and major BA in genetic vs acquired NICM were 10 of 52 vs 12 of 51, and 10 of 52 vs 4 of 51, respectively (both p=n.s.). However, MVA occurred more frequently in LMNA-NICM (eight of 23 vs two of 29 hypertrophic, p=0.015) and in previous myocarditis (nine of 21 vs three of 30 acute, p=0.016), while major BAs were particularly common in LMNA-NICM patients only (nine of 23 vs one of 29 hypertrophic, p=0.003). Different patterns of septal LGE were consistently retrospectively identified at baseline CMR: junctional and limited to the base in 79.3% of uneventful hypertrophic NICM; extended and focally transmural in LMNA-NICM with follow-up arrhythmias (both p<0.05); transitory in patients with acute myocarditis, who, differently from the post-myocarditis ones, showed follow-up arrhythmias only in the presence of unmodified LGE at follow-up CMR (five of 13, p=0.009).

Conclusion

Septal LGE was significantly associated with MVA at the 5-year follow-up in LMNA-NICM or previous myocarditis, and with major BA in LMNA-NICM only. These differences correlated with heterogeneous patterns of IVS LGE in different NICM.

Introduction

Late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has been associated with an increased risk of sudden cardiac death (SCD) in many genetic and acquired non-ischaemic cardiomyopathies (NICM) [1]. In particular, among genetic diseases, involvement of the interventricular septum (IVS) by LGE has been described in primary hypertrophic cardiomyopathy (HCM) [2] and NICM associated with mutations of the lamin A/C gene (LMNA) [3]; there was a negative prognostic role in both cases [4,5]. However, LGE may also selectively involve the IVS in acquired NICM, like in previous myocarditis (PM) patients with or without dilated cardiomyopathy [6]. Furthermore, as compared with other localisations, septal LGE has been associated with an adverse outcome in myocarditis patients [7]. However, the prognostic role of LGE is nowadays challenging in patients with acute myocarditis (AM), since potential reversibility of abnormal signals has been recently described [8].

Although ventricular arrhythmias (VA) may complicate any of the above NICM, a remarkable occurrence of bradyarrhythmias (BA) has only been reported in some of them, like LMNA-NICM [9]. However, no studies to date have been designed to comparatively evaluate the arrhythmic outcome in patients with septal LGE and different types of genetic and acquired NICM. Based on the pathophysiological distinction between LGE and myocardial fibrosis [10], it was hypothesised that septal LGE does not have the same impact on the arrhythmic outcome of patients with different forms of genetic and acquired NICM.