The Diagnostic and Prognostic Value of the 12-Lead ECG in Arrhythmogenic Left Ventricular Cardiomyopathy

Abstract

Background: Electrocardiographic findings in arrhythmogenic left ventricular cardiomyopathy (ALVC) have been limited to small studies.

Objectives: The authors aimed to analyze the electrocardiogram (ECG) characteristics of ALVC, to correlate ECG with cardiac magnetic resonance and genetic data, and to evaluate its prognostic value.

Methods: We reviewed data of 125 consecutive patients with ALVC (81.5% desmoplakin pathogenic/likely pathogenic variants). The composite endpoint of major arrhythmic events (MAEs) included sudden cardiac death, aborted sudden cardiac death, and appropriate implantable cardioverter-defibrillator shock. Predictors of MAE were evaluated with logistic regression.

Results: ALVC showed distinct ECG signs, including left posterior fascicular block (LPFB) (13.6%), pathological Q waves (26.4%), R/S ratio in V₁ ≥0.5 (26.4%), and SV1 + RV6 ≤12 mm and RI + RII ≤8 mm (44%). Fifteen (12%) patients had a normal ECG. MAE occurred in 35 patients (28%). In multivariable analysis, LPFB (OR: 4.7; 95% CI: 1.2-18.3), syncope (OR: 84.95; 95% CI: 14-496), transmural late gadolinium enhancement (OR: 9.95; 95% CI: 2.3-36), and right ventricular ejection fraction (OR: 0.92; 95% CI: 0.87-0.97) were the independent predictors of MAE. The model including these 4 variables achieved a remarkable predictive capability (area under the curve: 0.9). In the primary prevention scenario, with Cox regression, LPFB (HR: 3.98; 95% CI: 1.3-12.0), syncope (HR: 19.13; 95% CI: 5.8-63.0), and transmural late gadolinium enhancement (HR: 10.57; 95% CI: 2.9-38.0) were independent predictors of MAE.

Conclusions: In ALVC, ECG is a valuable diagnostic tool and may have a relevant prognostic role, since LFPB is a strong and independent predictor of MAE.

Keywords: ECG; arrhythmias; arrhythmogenic cardiomyopathy; cardiomyopathy; desmoplakin; desmosome; magnetic resonance imaging; prognosis; sudden cardiac death.

Graphical abstract

Figure 1

Electrocardiographic Findings in Patients With Arrhythmogenic Left Ventricular Cardiomyopathy (A) Electrocardiogram of patient #56 (19-year-old man, pathogenic variant in desmoglein-2 c.271G>T, p.Gly91Ter) shows left posterior fascicular block, a fragmented QRS in V₁ to V₃ and T-wave inversion in V₃ to V₅. (B) Electrocardiogram of patient #83 (71-year-old man, likely pathogenic variant in desmoglein-2 p.Val295Serfs∗6) displays global low QRS voltage, anterior T-wave inversion, and R/S ratio ≥0.5 in V₁ (red box). (C) Electrocardiogram of patient #19 (35-year-old man with pathogenic variant in desmoplakin c.5210delG p.Gly1737AspfsTer16) displays low QRS voltage in limb leads and pathological inferior Q waves (blue boxes). (D) Patient #86 (14-year-old man, pathogenic variant in plakophilin-2, c.1378+1G>C), had an aborted sudden cardiac death at presentation; his electrocardiogram shows left posterior fascicular block and T-wave inversion in V₁ to V₃. A sum of the R-wave in I to II ≤8 mm and SV₁ + RV₆ ≤12 mm, a R/S ratio ≥0.5 in V₁ are also present. All the electrocardiograms presented were performed at 25 mm/s with 1 mm/mV.

Figure 2

Electrocardiographic Changes During Follow-Up (A and B) Patient #38 is a man with a pathogenic variant in desmoplakin (deletion of the entire desmoplakin gene, 6p25.1-p24.3). Electrocardiogram at age 28 shows T-wave inversion in lateral leads. After 6 years, electrocardiogram shows the appearance of left posterior fascicular block (violet box) and T-wave inversion in leads V₂ to V₃ (asterisks). (C and D) Electrocardiograms of patient #45 (48-year-old man, likely pathogenic variant in desmoplakin c.860A>G, p.Asn287Ser) display the presence of low QRS voltages in lateral leads and the appearance over time of left posterior fascicular block and pathological Q waves in inferior leads (violet box). (E and F) Electrocardiogram of patient #108 (18-year-old man, pathogenic variant in desmoplakin c.2821C>T, P.Arg941∗) shows low QRS voltages in the lateral leads. After 4 years, the electrocardiogram shows the appearance of T-wave inversion in inferior leads and in V₃ to V₆ (asterisks), polymorphic premature ventricular beats.

Central Illustration

The Diagnostic and Prognostic Role of the Electrocardiogram in Arrhythmogenic Left Ventricular Cardiomyopathy ALVC = arrhythmogenic left ventricular cardiomyopathy; DSP = desmoplakin; ECG = electrocardiogram; LGE = late gadolinium enhancement; LPFB = left posterior fascicular block; LQRSV = low QRS voltages; MAE = major arrhythmic events; RVEF = right ventricular ejection fraction; TWI = T-wave inversion.