Ring-like patterns on imaging and sudden cardiac death: can ECG help stratify risk?

This editorial refers to ‘Arrhythmic risk stratification in patients with left ventricular ring-like scar’, by V. Parisi et al. doi:10.1093/eurjpc/zwae353 A ‘ring-like’ fibrosis pattern is a distinctive distribution of late gadolinium enhancement (LGE) seen as a subepicardial or midmyocardial band, affecting at least three contiguous segments of the left ventricle.1 This pattern is commonly associated with left ventricular cardiomyopathies linked to genetic mutations in DSP, FLNC, or DES, but it can also appear in phenocopies of these diseases.2 In recent years, this pattern has garnered increasing attention, particularly because it is often identified in young patients with only mildly reduced left ventricular ejection fraction (LVEF). Many of these individuals are asymptomatic for heart failure and maintain normal physical activity.3 However, this specific fibrosis distribution is closely linked to a heightened risk of sudden cardiac death (SCD).4 Chen and colleagues recently reported that, given an equivalent total scar burden, the ring-like fibrosis pattern carries a greater risk of life-threatening ventricular arrhythmias (VAs) compared with other common non-ischaemic fibrosis patterns.3 Muser and co-workers also noted that this pattern can also be present in young patients with apparent idiopathic premature ventricular complexes, increasing their risk of SCD.5 Moreover, this fibrosis pattern has been identified as a common cause of SCD among athletes, often eluding detection in routine echocardiographic screening.6,7 Despite increasing evidence that a ring-like fibrosis pattern heightens risk of VAs there are still no specific recommendations on how to stratify SCD risk in these patients.2 This is becoming a more common challenge in clinical practice, as the widespread use of cardiac magnetic resonance imaging (MRI) in the past decade8 has led to more frequent identification of this pattern. In this issue of Journal,9 Parisi et al. present a collaborative retrospective study conducted across six Italian centres, involving 115 patients exhibiting a ring-like pattern on MRI. Notably, all patients underwent genetic analysis. This population consisted of young individuals, with a mean age of 39 years, all of whom had a slightly reduced LVEF and, frequently, non-dilated left ventricles. DSP and FLNC variants were the most common genetic findings. Over a follow-up period exceeding 4 years, survival, free from life-threatening VA, was 60%. The authors assessed baseline characteristics associated with arrhythmic risk, finding that left ventricular dilatation, as well as certain ECG anomalies such as the presence of anterior Q waves and a widened QRS complex, are independently associated with arrhythmic risk. Moreover, they noted that patients with a completely normal 12-lead ECG represented a subgroup with a very low risk of ventricular events. These findings are particularly welcome, as they mark the initial steps towards risk stratification in patients displaying a ring-like MRI pattern. However, to properly interpret this study, it is essential to recognize certain research constraints. First, the absence of a validation cohort suggests that these results should be interpreted with caution. Additionally, the retrospective design may introduce selection bias. The authors applied inclusion criteria to select patients with a high probability of familiar left ventricular cardiomyopathy. As a result, 73% of the patients had a pathogenic or likely pathogenic (P/LP) variant, which is not representative of the broader clinical population who are identified with a ring-like pattern.10 The fact that no association was found in this study between genetic status and arrhythmic risk must also be interpreted with caution in this selected population. It is well known that in patients with non-ischaemic cardiomyopathy (NICM), carriers of specific mutations present a significantly higher risk of VAs compared with those without these mutations.11 Moreover, the association of a ring-like pattern with DSP/FLNC mutations identifies a population at particularly high risk for SCD.12 In fact, current guidelines consider the presence of specific genetic variants as a risk factor in patients with NICM, supporting the recommendation for ICD implantation for primary prevention of SCD in patients with these mutations, even in the absence of severely reduced LVEF.13 Therefore, while the genetic analysis of all patients is a strength of this manuscript, the lack of association with clinical outcomes likely reflects study design, rather than being a clinically meaningful observation. Another finding that should be interpreted with caution is the limited predictive capability of MRI. The authors did not find significant differences between patients who experienced VAs and those who did not, with respect to either the total number of segments affected by LGE or its distribution. However, we cannot rule out the possibility that a more comprehensive scar characterization, beyond a semi-quantitative approach, might have produced different results. Scar heterogeneity, which refers to the varying composition of dense scar tissue vs. border zone (BZ) tissue, is a well-established predictor of ventricular events. In a recent study, Leyva et al. demonstrated that BZ mass is a strong predictor of SCD in patients with NICM and provides additional prognostic value beyond the total fibrosis mass.14 Moreover, MRI post-processing can identify the presence of viable myocardial strands within the scar, known as BZ corridors or channels. This qualitative distribution of BZ tissue in myocardial scars independently predicts life-threatening VA in patients with NICM.15 Unfortunately, neither the quantification of the BZ nor its three-dimensional structure has been analysed. Despite inherent limitations, this study provides valuable new insights into arrhythmic risk classification for patients with a ring-like fibrosis pattern. The identification of simple markers, such as a normal 12-lead ECG, to categorize patients into lower-risk groups is particularly promising. Beneath its apparent simplicity, 12-lead ECG analysis may conceal crucial clues for SCD risk stratification.16,17 For instance, a straightforward ECG estimation of left ventricular hypertrophy has been associated with SCD risk in patients with hypertrophic cardiomyopathy.18 Additionally, similar to what Parisi et al. propose in their paper, a previous ECG-based risk score has been shown to effectively identify patients at risk for SCD, particularly for those with LVEF >35%.19 Although further studies are necessary to validate these findings, they represent a significant step forward in addressing a complex and common challenge faced by clinicians. It remains to be seen whether combining simple electrocardiographic criteria with genetic data, alongside qualitative scar analysis, will enhance personalized and more precise SCD risk stratification in patients with a ring-like fibrosis pattern. Conflict of interest: none declared.