Final Diagnosis -- Arrhythmogenic Right Ventricular Cardiomyopathy

FINAL DIAGNOSIS:

ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY

DISCUSSION:

The patient was a young woman who presented with a presumed viral induced cardiomyopathy. Her history included a sudden onset of atrial fibrillation and ventricular tachycardia following a flu-like illness. Her father and two sisters died at a young age from presumed cardiac etiology. Furthermore, a third sister had a nearly identical presentation which required heart transplantation.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) typically presents as a sudden debilitating right ventricular myopathy with ventricular tachycardia, syncopal attacks and sudden death following a recent flu-like illness. It is a familial condition linked to chromosomes 1, 2 and 14 that is characterized by specific arrhythmias. ARVC occurs in families, and it is inherited as an autosomal dominant trait with variable penetrance and clinical expression.

ARVC has been reported as the leading cause of sudden death in young athletes. Even mild forms of the disease may be life-threatening by jeopardizing the electrical order of the heart during effort.

The most prominent pathologic feature of ARVC is fatty infiltration of ventricular myocardium. Research has implicated type B coxsackieviruses as the probable agent which presumably induces myocyte loss with replacement by infiltrating fat cells in these predisposed patients. However, a recent report suggests that the disease may actually be a myocyte transdifferentiation into adipocytes, as opposed to myocyte-loss and adipose-replacement as has been previously believed. The myocyte-loss/transdifferentiation can be postulated to affect the transduction of electrical impulses, and possibly the sinoatrial node itself, leading to arrhythmias.

In this patient, the gross and microscopic autopsy findings showed an anatomic correlate of atrial fibrillation: an atrial mural thrombus. Furthermore, there was extensive fatty infiltration of the right atrium, right ventricle and left ventricle. The myocytes adjacent to the adipose tissue infiltrate showed multiple sarcoplasmic vacuoles, as would be expected for ARVC.

ARVC can be clinically covert and difficult to diagnose or suspect. The combination of clinical and family history is crucial to the diagnosis of ARVC. Most patients with ARVC have clinical clues to the diagnosis in their own medical history or family history. With increased awareness of the diagnostic criteria, hopefully young patients with occult ARVC will be identified in the future and their death prevented.

REFERENCES:

1. d'Amati, G., Gioia, C. R., Giordano, C., and P. Gallo. "Myocyte Transdifferentiation: a possible pathogenetic mechanism for arrhythmogenic right ventricular cardiomyopathy." Arch Pathol Lab Med Feb 2000 124, 287-90.
2. Fornes, P., Ratel, S., and D. Lecomte. "Pathology of Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia-An autopsy study of 20 forensic cases." J Forensic Sci 1998 Jul 43:4 777-83.
3. Rampazzo, A, Nava, A, Danieli, G.A., Buja, G., Daliento, L., Fasoli, G., Scognamiglio, R., Corrado, D., and G.Thiene. "The gene for arrhythmogenic right ventricular cardiomyopathy maps to chromosome 14q23-q24." Hum Mol Genet 1994 Jun 3:6 959-62.
4. Thiene, G., Nava, A., Corrado, D., Rossi, L., and N. Pennelli. "Right ventricular cardiomyopathy and sudden death in young people." New England J Med 1988 Jan 318:3 129-133.
5. Grumbach, I.M., Heim, A., Vonhoff, S., Stille-Siegener, M., Mall, G., Gonska, B.D., Kreuzer, H., Andreas, S., and H.R. Figulla. "Coxsackievirus genome in myocardium of patients with arrhythmogenic right ventricular dysplasia/ cardiomyopathy." Cardiology 1998 89:241-45.
6. Thiene, G., Basso, C., and D. Corrado. "Is prevention of sudden death in young athletes feasible?" Cardiologia 1999 Jun 44:6 497-505.
7. Cotran, R.S., Kumar, V., and T. Collins, eds. Robbins Pathologic Basis of Disease, 6th ed. 1999.

Contributed by J. Thomas Molina, MD, PhD, Larry Nichols, MD, and Bernard Klionsky, MD