Familial polymorphic ventricular arrhythmias: a quarter century of successful medical treatment based on serial exercise-pharmacologic testing.

OBJECTIVES: We sought to determine whether objective tests of antiarrhythmic drug efficacy could produce favorable short- and long-term outcomes in a family with idiopathic malignant ventricular arrhythmias. BACKGROUND: In 1973 a family presented with a history of several generations of syncopal spells and sudden death. Some individuals had nonspecific electrocardiographic (ECG) changes. Their QT intervals were normal at rest and with exercise. Autopsies in two young family members showed no cardiac abnormalities, specifically no evidence of arrhythmogenic right ventricular dysplasia, other cardiomyopathy, myocarditis or gross abnormality of the conduction system. METHODS: Available family members had screening ECGs. Symptomatic members had a battery of tests, including electrophysiologic studies, ambulatory ECGs, audiograms, exercise stress testing, serum catecholamine levels during rest and exercise and isoproterenol infusion. Serial exercise-pharmacologic testing was performed in symptomatic family members until induction of an arrhythmia during exercise required higher work loads or became impossible. RESULTS: Arrhythmias were not induced during electrophysiologic studies. In several family members tested, ventricular premature beats and then rapid polymorphic ventricular arrhythmias occurred whenever the sinus rate exceeded 130 beats/min. Emotional stress, isoproterenol infusion and exercise all elicited similar arrhythmias. Catecholamine levels during exercise were, however, unequivocally normal in two of three family members tested. Beta-blockers appeared to be the most effective pharmacologic agent for prevention of these arrhythmias. The efficacy of treatment has been confirmed during a follow-up of 25 years. CONCLUSIONS: This family appears to have catecholamine hypersensitivity as the basis for their ventricular arrhythmias. Guided therapy using serial exercise-pharmacologic testing provided reliable protection for this familial ventricular arrhythmia during a 25-year follow-up.

Atrial myxoma: a tumour in search of its origins.

OBJECTIVE: To determine whether atrial myxomas express antigens suggesting a neural origin. DESIGN: A retrospective analysis based on immunohistochemical examination of myxoma tissue. SETTING: Atrial myxomas excised by two tertiary referral cardiothoracic surgical units. SUBJECTS: 24 excised atrial myxomas. Three were from known cases of familial myxoma syndrome. METHODS: Immunohistochemical identifications of three neuroendocrine markers (protein gene product (PGP) 9.5, neurone specific enolase (NSE), synaptophysin) and S100 antigen; CD34 and von Willebrand factor; and chi smooth muscle actin to identify possible Schwann cell differentiation, endothelial cells, and smooth muscle cells respectively. RESULTS: The myxoma cells were PGP 9.5 positive in 18, S100 positive in 16, and NSE positive in 12. Of the 12 NSE positive myxomas seven were synaptophysin positive. All tumours that were NSE positive were also S100 and PGP 9.5 positive. The tumour surface was partially covered by myxoma cells, partly by endothelial cells. CONCLUSION: The histological appearances of myxomas with stellate cells embedded within a loose connective tissue stroma, abundant basophil cell infiltration, and the presence of pericellular type IV collagen are similar to nerve sheath tumours (neurofibromas) at other sites. A significant proportion of myxomas also express Schwann cell and neuroendocrine differentiation markers. These features cannot prove the origin of myxomas because tumours may develop aberrant phenotype expression but they do accord with the view that myxomas originate from endocardial sensory nerve tissue.