Table1:
Clinical characteristics of family A and family B.
| ECG/Signal-averaged ECG |
|||||||||
|---|---|---|---|---|---|---|---|---|---|
| Individual | Age of Investigation | Clinical History | Family History/Genetics | Structural and Functional Alterations by CMR or Echocardiography | Tissue Characterization on RV-Biopsy or Autopsy | Repolarization Abnormalities | Depolarization Abnormalities | Arrhythmias | TF-Score Major/Minor Fullfilled Yes/No |
| Family A | |||||||||
| III-1 | 25 | asympomatic, ICD implanted because of possible diagnosis | (+/−) ILK: p.H77Y; 1st degree relative died suddenly with ACM confirmed on autopsy | Anterior RV wall appears thinned with fat infiltration, no akinesis or dyskineses, normal RVEF | 1/6 biopsy samples showed focal fatty infiltration and fibrosis | Non-specific T-wave abnormalities | None | None | 1M/1m: No |
| 33 | remains asymptomatic. ICD explanted after lead fracture | (+/−) ILK: p.H77Y; 1st degree relative died suddenly with ACM confirmed on autopsy | Preserved left and right ventricular function, estimated RVEF: 55%, RV not dilated | All biopsies non-diagnostic for ARVC | N/A | None | None | 1M: No | |
| III-2 | 22 | clinically diagnosed with ACM, largely asympomatic, ICD implanted | (+/−) ILK: p.H77Y; 1st degree relative died suddenly with ACM confirmed on autopsy | Anterior RV wall is thinned with fat infiltration, no akinesis or dyskineses, mildly reduced RVEF, changes more pronounced than in sibs | Biopsies show focal fatty infiltration and fibrosis | None | 2/3 positive for late potenials on SA-ECG | None | 2M / 1m: Yes |
| III-3 | 16 | cardiac arrest during bowel surgery (ischemic bowel with lymphoid hyperplasia), signs of ACM diagnosed on autopsy | (+/−) ILK: p.H77Y | N/A | RV slightly dilated, RV free wall quite thin (0.3–0.1 cm in thickness). Fatty infiltration into RV free wall. Extensive fatty infiltratiorr in RV, some fibrosis. Focal fatty infiltration of AV node and bundle of his | N/A | N/A | N/A | >2M, confirmed ACM on autopsy: Yes |
| III-4 | 14 | clinically diagnosed with ACM, largely asympomatic, ICD implanted | (+/−) ILK: p.H77Y; 1st degree relative died suddenly with ACM confirmed on autopsy | Anterior RV wall appears thinned with fat infiltration, no akinesis or dyskinesis, normal RVEF | Biopsies with moderate interstitial fibrosis and with fatty infiltration | None | None | Rare PVCs, no arrhythmias | 2M: Yes |
| III-5 | 10 | no clinical signs of ACM | (+/−) ILK: p.H77Y; 1st degree relative died suddenly with ACM confirmed on autopsy | Normal RV size and systolic function. No wall motion abnormalities. Normal LV size, mass and systolic function. | N/A | None | None | None | 1M: No |
| II-1 | 48 | No cardiac concerns | (−/−) ILK: p.H77Y; 1st degree relative died suddenly with ACM confirmed on autopsy | Normal RV and LV Size and systolic function. | N/A | None | 2/3 positive for late potenials on SA-ECG | Rare PVCs, no arrhythmias | 1M/1m: No |
| II-2 | 51 | No cardiac concerns | (+/−) ILK: p.H77Y; 1st degree relative died suddenly with ACM confirmed on autopsy | Normal RV and LV Size and systolic function. | N/A | None | None | None | 1M: No |
| Family B | |||||||||
| II-1 | 14 | clinically diagnosed with ACM, syncope, ICD implanted | (+/−) ILK: p.H33N (de novo) | RV-dyskinesis with reduction of RV ejection fraction (RV-EF: 45%), no aneurysms, no LV impairment | N/A | Negative T-waves in V1-V3 | 2/3 positive for late potentials on SA-ECG | > 500 PVCs and three triplets in 24h Holter | 2M/3m:Yes |
| I-1 | 45 | No cardiac concerns | (−/−)p.H33N; 1st degree relative with ACM | Normal RV and LV size and systolic function. | N/A | None | None | None | 1M: No |
| I-2 | 43 | No cardiac concerns | (−/−)ILK: p.H33N; 1st degree relative with ACM | Normal RV and LV size and systolic function. | N/A | None | None | None | 1M: No |
CMR, cardiac magnetic resonance imaging; RV-EF, right ventricular ejection fraction; LV, left ventricle; RV, right ventricle; PVCs, premature ventricular beats; LBBB, left bundle branch block; RBBB, right bundle branch block; ILK, integrin linked kinase; ICD, implantable cardioverter defibrillator; ACM, arrhythmogenic cardiomyopathy; SA-ECG, signal averaged electrocardiogram; TF-Score, task force score; M, major; m, minor. Diagnostic terminology for revised criteria 2010 (ref. 2): definite diagnosis: 2 major or 1 major and 2 minor criteria or 4 minor from different categories; borderline: 1 major and 1 minor or 3 minor criteria from different categories; possible: 1 major or 2 minor criteria from different categories.