Correspondence

Case 37-2005: A Man with Cardiac Arrest while Sleeping

N Engl J Med 2006; 354:1432-1433March 30, 2006

Article

To the Editor:

In the Case Records presented in the December 8 issue,1 the statement by the discussant, “the only identified cause of Brugada syndrome is an abnormality in the cardiac sodium channel,” as well as the entire discussion, would have been more useful if some additional data had been added. An article on the Online Mendelian Inheritance in Man Web site (www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=601144) clearly establishes that this syndrome can also be associated with organic heart disease, as described previously.2,3 The patient whose case was discussed had neither an SCN5A abnormality nor a family history of sudden death. He did not undergo right ventricular angiography, endomyocardial biopsy, or cardiac magnetic resonance imaging to exclude the presence of right ventricular abnormalities. No autopsy was performed after the patient died. At present, to my knowledge, there is not a single published case of a person with the Brugada syndrome who, when the cardiac pathological findings at autopsy were described in detail, had a normal heart. All the patients examined up to the present time have had some structural cardiac abnormality.4,5 More evidence-based data are needed before the sudden death in this case is ascribed to a functional abnormality.

Bortolo Martini, M.D.
Boldrini Hospital, 36016 Thiene, Italy
bmartini@ulss4.veneto.it

5 References

1. 1

   Case Records of the Massachusetts General Hospital (Case 37-2005). N Engl J Med 2005;353:2492-2501
   Full Text | Web of Science | Medline

2. 2

   Martini B, Nava A, Thiene G, et al. Ventricular fibrillation without apparent heart disease: description of six cases. Am Heart J 1989;118:1203-1209
   CrossRef | Web of Science | Medline

3. 3

   Frustaci A, Priori SG, Pieroni M, et al. Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome. Circulation 2005;112:3680-3687
   CrossRef | Web of Science | Medline

4. 4

   Martini B, Nava A. 1988-2003: Fifteen years after the first Italian description by Nava-Martini-Thiene and colleagues of a new syndrome (different from the Brugada syndrome?) in the Giornale Italiano di Cardiologia: do we really know everything on this entity? Ital Heart J 2004;5:53-60
   Medline

5. 5

   Coronel R, Casini S, Koopmann TT, et al. Right ventricular fibrosis and conduction delay in a patient with clinical signs of Brugada syndrome: a combined electrophysiological, genetic, histopathologic, and computational study. Circulation 2005;112:2769-2777
   CrossRef | Web of Science | Medline

Author/Editor Response

Dr. Martini raises some interesting points, although we feel that he has taken a quotation from our article out of its original context. The full sentence emphasized our limited understanding of the molecular basis of the syndrome, not its functional or structural manifestations. In their original description, Brugada and Brugada stated that they found no evidence of structural heart disease with the use of standard testing.1 However, there has been an ongoing evolution in our understanding of the phenotype of the Brugada syndrome. As noted, two recent elegant studies suggest that, even among patients with identified mutations in the SCN5A sodium-channel gene, there may often be structural myocardial abnormalities that escape detection on routine testing.2,3

We agree that a thorough evaluation with a broad range of diagnostic techniques is often indicated in the case of patients with idiopathic sudden death. Our diagnosis was based on the clinical evidence available, and we accept the fact that alternative diagnoses were not definitively excluded. Had this patient had a meaningful neurologic recovery, further testing would have been performed.

Keith Marill, M.D.
Patrick Ellinor, M.D., Ph.D.
Alex Manini, M.D.
Massachusetts General Hospital, Boston, MA 02114

3 References

1. 1

   Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome: a multicenter report. J Am Coll Cardiol 1992;20:1391-1396
   CrossRef | Web of Science | Medline

2. 2

   Frustaci A, Priori SG, Pieroni M, et al. Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome. Circulation 2005;112:3680-3687
   CrossRef | Web of Science | Medline

3. 3

   Coronel R, Casini S, Koopmann TT, et al. Right ventricular fibrosis and conduction delay in a patient with clinical signs of Brugada syndrome: a combined electrophysiological, genetic, histopathologic, and computational study. Circulation 2005;112:2769-2777
   CrossRef | Web of Science | Medline