Integrating electrocardiographic and echocardiographic findings in predicting desmoplakin gene variants in dilated and nondilated left ventricular cardiomyopathy

Abstract Background Desmoplakin-related cardiomyopathy (DSP-CM) can present with either dilated or nondilated left ventricular (LV) phenotypes and is characterized by a high arrhythmic burden, placing patients at significant risk of sudden cardiac death. Although previous studies have highlighted the diagnostic value of ring-like late gadolinium enhancement (LGE) patterns on cardiac magnetic resonance (CMR) in DSP-CM, CMR is not always readily available. Aim of the study: This study aimed to evaluate whether echocardiographic and electrocardiographic (ECG) parameters could help identify DSP-CM in clinical settings where CMR may be less accessible. Methods We prospectively enrolled all consecutive patients diagnosed with DSP-CM harboring pathogenic or likely pathogenic DSP variants evaluated at our center. A control group consisted of age-matched patients with dilated cardiomyopathy (DCM) of other various etiologies. All participants underwent detailed ECG and echocardiographic evaluations. ECG tracings were analyzed using the EP Calipers application to assess QRS duration, QRS fragmentation (pattern classified as RSR’, RnS, Rn, RSn, RSR’S’ – Figure 1) and dispersion calculated as the difference between maximal and minimal QRS duration in the standard 12-lead ECG, and conduction defects. Results A total of 18 patients with DSP-CM and 50 with DCM (15 TTN, 4 LMNA, 2 DMD, and 27 negative genetic tests via next-generation sequencing) were included and matched for age (39.4±12.1 in DSP-CM vs. 39.1±14.2 in DCM; p=NS). Notably, DSP-CM was more common among women (66% vs. 38%; p=0.03). Compared to DCM, DSP-CM patients exhibited lower LV end-diastolic volumes, higher LVEF, and a nondilated right ventricle with similar systolic function (see Table 1). However, ECG changes were more pronounced in DSP-CM: wider QRS intervals, higher QRS dispersion, more frequent left axis deviation, and a higher incidence of low QRS voltage. Using receiver operating characteristic (ROC) analysis, we derived predictive cutoffs for each significant parameter (QRS duration 103.5 ms, QRS dispersion 9.5 ms, LVEF 37.5%, LV end-diastolic volume 67 mL, presence of RnS or Rn pattern, left anterior fascicular block, and low voltage). Each parameter was assigned 1 point to build a predictive score. This score demonstrated an area under the curve (AUC) of 0.894, and a cutoff of ≥3 points predicted the presence of a DSP variant with 88.9% sensitivity and 74% specificity. Conclusions Patients with DSP-CM typically present with smaller, less dysfunctional LV relative to other forms of DCM; however, their ECG abnormalities are more pronounced. In clinical scenarios where CMR may be limited, this combination of echocardiographic and ECG findings can serve as a valuable tool to prompt further genetic investigation for DSP gene variants.Figure 1.QRS fragmentation patterns Table 1