Quantitative Approach to Fragmented QRS in Arrhythmogenic Cardiomyopathy: From Disease towards Asymptomatic Carriers of Pathogenic Variants

Figure 1. (A): Resting electrocardiography (ECG) (25 mm/s, 10 mm/mV, 150 Hz) of a 43 year old female patient with ACM and a pathogenic plakophilin 2 (PKP2) variant (c.2368T > C p.Cys796Arg)) who presented with recurrent sustained ventricular tachycardia (VT). She underwent unsuccessful VT ablation and afterwards an implantable cardioverter defibrillator (ICD) implantation. During follow-up, she developed therapy resistant heart failure due to RV failure and underwent heart transplantation. Her resting ECG without antiarrhythmic drugs showed sinus bradycardia, prolonged QRS duration (160 ms) due to intraventricular conduction disorder, prolonged terminal activation duration (TAD, 110 ms) and T wave inversion in leads II, III, aVF, V1–V6. There is marked fragmentation of the QRS complexes in the inferior- and precordial leads. (B): Resting ECG (25 mm/s, 10 mm/mV, 150 Hz) of a 28 year old male who is a carrier of a pathogenic PKP2 variant (c.379C > T p.(Gln133 *)) and a variant of unknown significance in PKP2 (c.2615C > T p.(Thr872Ile)). He was included in the pathogenic variant carrier group. The patient was referred for family cascade screening and is asymptomatic. Cardiac MRI showed a…

Figure 2. This figure shows recordings of leads V1–V3 from a patient with arrhythmogenic cardiomyopathy. All shown QRS complexes have fQRS according to the definition by Das [4]. The quantitative fQRS (Q-fQRS) counting is indicated by black arrows. Each arrow represents a positive or negative deflection counted as fractionated signal and was reproducible between the first and second QRS complex of each lead. Lead V1, V2, and V3 have a Q-fQRS count being 7, 8, and 11, respectively. The Q-fQRS count for leads V1–V3 in this figure add up to 26 (for the total Q-fQRS is summation of deflections in all 12 ECG leads required, these leads are not shown).

Figure 3. ACM = arrhythmogenic cardiomyopathy; ECG = electrocardiography; fQRS = fragmented QRS; SVA = sustained ventricular arrhythmia.

Figure 4. PKP2 = Plakophilin-2; DSG2 = Desmoglein-2; DSC2 = Desmocollin-2; PLN = Phospholamban; Polygenetic = multiple pathogenic ACM-related variants, Unknown = no pathogenic variant identified using genetic screening.