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CLINICAL RESEARCH: IMAGING IN HEART RHYTHM DISORDER

Morphologic Variants of Familial Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

A Genetics–Magnetic Resonance Imaging Correlation Study

Darshan Dalal, MD, MPH^_*,_*, Harikrishna Tandri, MD^_*, Daniel P. Judge, MD^_*, Nuria Amat, MS^_*, Robson Macedo, MD, Rahul Jain, MD^_*, Crystal Tichnell, MGC^_*, Amy Daly, MS^_*, Cynthia James, PhD, ScM^_*, Stuart D. Russell, MD^_*, Theodore Abraham, MD^_*, David A. Bluemke, MD, PhD and Hugh Calkins, MD^_*

^_* Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland
Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, Maryland

Manuscript received July 8, 2008; revised manuscript received November 5, 2008, accepted December 3, 2008.

^_* Reprint requests and correspondence: Dr. Darshan Dalal, 600 North Wolfe Street, Carnegie 592, Baltimore, Maryland 21209 (Email: ddalal1{at}jhmi.edu).

Objectives: The purpose of this study was to determine the extent of left ventricular (LV) involvement in individuals predisposed to developing arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), and to investigate novel morphologic variants of ARVD/C.

Background: The discovery of desmosomal mutations associated with ARVD/C has led researchers to hypothesize equal right ventricular (RV) and LV affliction in the disease process.

Methods: Thirty-eight (age 30 ± 17 years; 18 males) family members of 12 desmosomal mutation-carrying ARVD/C probands underwent genotyping and cardiac magnetic resonance imaging (CMR). The CMR investigators were blinded to clinical and genetic data.

Results: Twenty-five individuals had mutations in PKP2, DSP, and/or DSG2 genes. RV abnormalities were associated with the presence of mutation(s) and with disease severity determined by criteria (minor = 1; major = 2) points for ARVD/C diagnosis. The only LV abnormality detected, the presence of intramyocardial fat, was present in 4 individuals. Each of these individuals was a mutation carrier, whereas 1 had no previously described ARVD/C-related abnormality. On detailed CMR, a focal "crinkling" of the RV outflow tract and subtricuspid regions ("accordion sign") was observed in 60% of the mutation carriers and none of the noncarriers (p < 0.001). The sign was present in 0%, 37%, 71%, and 75% of individuals who met 1, 2, 3, and 4+ criteria points, respectively (p < 0.01).

Conclusions: Despite a possible LV involvement in ARVD/C, the overall LV structure and function are well preserved. Independent LV involvement is of rare occurrence. The accordion sign is a promising tool for early diagnosis of ARVD/C. Its diagnostic utility should be confirmed in larger cohorts.

Key Words: cardiomyopathy • arrhythmia • magnetic resonance imaging • genetics • diagnosis

Abbreviations and Acronyms   ARVD/C = arrhythmogenic right ventricular dysplasia/cardiomyopathy   CMR = cardiac magnetic resonance imaging   EDV = end-diastolic volume   EF = ejection fraction   ESV = end-systolic volume   LV = left ventricle/ventricular   ROC = receiver-operating characteristic   RV = right ventricle/ventricular   RVOT = right ventricular outflow tract

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