Differential profile and biochemical effects of antiautonomic membrane receptor antibodies in ventricular arrhythmias and sinus node dysfunction.

BACKGROUND: The relationship between anti-beta-adrenergic (anti-betaR) and anti-M(2)-cholinergic (anti-M2R) receptor antibodies (Abs) and cardiac arrhythmias and their biochemical effects have not been systematically investigated. METHODS AND RESULTS: We studied 41 patients, 28 with ventricular arrhythmias (primary or due to Chagas' heart disease or idiopathic dilated cardiomyopathy; group I), 13 with sinus node dysfunction (primary or caused by Chagas' heart disease; group II), and 10 healthy controls (group III). The chronotropic effects of the IgG and immunopurified anti-beta(1)RAbs or anti-M2RAbs were assessed on cultured cardiomyocytes before and after exposure to atropine and propranolol. The biochemical effects of the IgG from 9 patients from group I, 6 from group II, and 6 controls were evaluated on COS7 cells transfected with genes encoding for beta(1),beta(2)-adrenergic receptors (cAMP increment) or M(2)-cholinergic receptors (phosphatidylinositol increment). The IgG from group I patients exerted a positive chronotropic action, with a high prevalence of anti-betaRAbs (75%) and low prevalence of anti-M2RAbs (10.7%) and induced a clear-cut and long-lasting increment in cAMP. The IgG from group II patients depressed chronotropism, with a high prevalence of anti-M2RAbs (76.9%) and low prevalence of anti-betaRAbs (15.4%) and evoked a marked augmentation of phosphatidylinositol. CONCLUSIONS: Our results demonstrate a strong correlation between anti-betaRAbs and ventricular arrhythmias and anti-M2RAbs and sinus node dysfunction. Anti-betaRAbs increase and anti-M2RAbs inhibit cAMP production. These findings offer new insight into the etiology and pathophysiology of cardiac arrhythmias, with therapeutic implications.

Pre-excitation syndrome and hypertrophic cardiomyopathy.

Among one hundred and five consecutive patients with pre-excitation (PE) syndrome studied during a 10-year period, eight had an associated hypertrophic cardiomyopathy (HC) (7.62 per cent), eight had a coronary heart disease (7.62 per cent) and nine had a hypertensive heart disease (8.57 per cent). Of the eight patients with HC, four had an asymmetrical form (three of them with an obstructive component), and four a symmetrical form. Seven of these patients had a Wolff-Parkinson-White (WPW) type of PE and the remainder a Lown-Ganong-Levine type of PE. The incidence of paroxysmal tachycardias in the total group was 56.2% (61/105) and in the patients with associated HC was 62.5% (5/8). One of these latter patients had a concomitant brady-tachy syndrome and a severe obstructive form of HC. He was surgically treated (septal myomectomy and section of accessory atrioventricular pathway). The ECGs and VCGs of the seven patients with the HC-WPW type of PE association showed the coexistence of incomplete left bundle branch block of left ventricular hypertrophy patterns. The eight patients with associated HC were closely followed up from two to seven years (total follow-up period 435 patient/months). One of them died suddenly during the 40th month of follow-up. This study suggests that: 1) HC-PE association is not infrequent; 2) the incidence of paroxysmal tachycardias in the subgroup is quite similar to that presented in isolated PE; and 3) the electrocardiographic and vectorcardiographic changes in the HC-WPW type of PE association are highly specific.