Catecholaminergic polymorphic ventricular tachycardia: RYR2 mutations, bradycardia, and follow up of the patients.

BACKGROUND: The aim of the study was to assess underlying genetic cause(s), clinical features, and response to therapy in catecholaminergic polymorphic ventricular tachycardia (CPVT) probands. METHODS AND RESULTS: We identified 13 missense mutations in the cardiac ryanodine receptor (RYR2) in 12 probands with CPVT. Twelve were new, of which two are de novo mutations. A further 11 patients were silent gene carriers, suggesting that some mutations are associated with low penetrance. A marked resting sinus bradycardia off drugs was observed in all carriers. On beta blocker treatment, 98% of the RYR2 mutation carriers remained symptom free with a median follow up of 2 (range: 2-37) years. CONCLUSION: CPVT patients with RYR2 mutation have bradycardia regardless of the site of the mutation, which could direct molecular diagnosis in (young) patients without structural heart disease presenting with syncopal events and a slow heart rate but with normal QTc at resting ECG. Treatment with beta blockers has been very effective in our CPVT patients during initial or short term follow up. Given the risk of sudden death and the efficacy of beta blocker therapy, the identification of large numbers of RYR2 mutations thus calls for genetic screening, early diagnosis, and subsequent preventive strategies.

[Catecholinergic ventricular tachycardia in children]. / Tachycardies ventriculaires catécholergiques chez l'enfant.

Catecholinergic ventricular tachycardia is an adrenergic induced polymorphic ventricular arrhythmia. It occurs in infancy and is responsible for syncope and sudden death in the absence of any morphological cardiac abnormality. Without treatment the mortality in catecholinergic ventricular tachycardia is very high. We report genetic and clinical data from 25 cases of catecholinergic ventricular tachycardia referred with syncope (n=19) or resuscitated sudden death during exercise (n=6). A family history from the 25 families identified 41 apparent subjects considered as being clinically affected, with an average age of 30 +/- 10 years (11 to 62 years). Analysis of the RyR2 gene showed mutations in 13 of the 25 cases and in 39 of apparent subjects. With betablocker treatment (nadolol: 1.6 +/- 0.15 mg/kg), 96% of patients remained asymptomatic over an average follow-up of between 7.5 +/- 1.5 years, although some of them continued to display polymorphic ventricular extrasystoles on exercise. Nevertheless, 12% of the cases suffered sudden death or further syncope during follow-up. An automatic defibrillator was implanted in 2 patients who had a RyR2 mutation. High dose betablockers are effective in preventing serious rhythm disturbance in children. In adolescence, implanting an automatic defibrillator should be discussed in cases with a history of syncope or resuscitated sudden death. We confirm the importance of genetic studies in these families at high risk of sudden death.

Immediate and mid-term results of repeat percutaneous mitral commissurotomy for restenosis following earlier percutaneous mitral commissurotomy.

AIMS: This study assessed the results of repeat percutaneous mitral commissurotomy for mitral restenosis following a first procedure. METHODS AND RESULTS: Repeat balloon commissurotomy was performed in 53 patients who had symptomatic restenosis a mean of 6+/-2 years (2-11) after a successful first procedure; seven patients had mildly calcified valves. All patients had restenosis with a fusion of both commissures as assessed by echocardiography. A double-balloon was used in one case and the Inoue technique in 52. Complications were stroke in one patient and severe mitral regurgitation (Sellers grade 3) in two. Valve area increased from 1.03+/-0.22 to 1.82+/-0.21 cm(2)(P<0.0001) as assessed by planimetry. Good immediate results, defined as valve area >/=1.5 cm(2)with no regurgitation >2/4, were obtained in 48 patients (91%). The 5-year survival rate without operation and in NYHA class I or II was 69+/-11% in the whole population, and 76+/-11% in the 48 patients who had had good immediate results. CONCLUSION: This study suggests that repeat balloon commissurotomy is a valid treatment for symptomatic restenosis after a first successful procedure. It gives good results in patients selected on the basis of favourable characteristics and the echocardiographic analysis of the mechanism of restenosis.

[Adams-Stokes syncope disclosing a crisis of rheumatic fever. Apropos of a case]. / Syncope d'Adams Stokes révélant une crise de rhumatisme articulaire aigu. A propos d'un cas.

A high degree atrioventricular block (AVB) is an exceptional finding during an acute episode of rheumatic fever (RF). The authors report a case of complete syncopal AVB requiring a temporary pacemaker, representing the first episode of RF.

[Contribution of doppler echocardiography to the diagnosis of the first attack of acute rheumatic fever]. / Apport de l'échographie-doppler cardiaque au diagnostic de la première poussée de rhumatisme articulaire aigu.

Since 1944, the Jones criteria for the diagnosis of acute rheumatic fever have been regularly revised to integrate technical and diagnostic innovations. Echographic and Doppler criteria, however, remain unrecognised due to valvular insufficiency in healthy subjects. The aim of this study was to determine the cardiac lesions occurring in acute rheumatic fever and the diagnostic value of Doppler echocardiography. One hundred patients with an average age of 10 years were admitted to hospital because of a first attack of acute rheumatic fever between January 1991 and September 1992. Eighty-six had articular signs, 5 had chorea, but none had cutaneous lesions. Forty-seven murmurs of mitral insufficiency (MI) and eight of aortic insufficiency (AI) were detected; 10 children had signs of cardiac failure. Conduction defects were recorded in 12 cases. Echocardiography showed 7 pericardial effusions; often, the left heart chambers were dilated without alteration of the fractional shortening. The commonest lesions of the mitral valve were thickening of the two leaflets, the reduced mobility of the posterior leaflet, the rigidity of the anterior leaflet and 2 cases of ruptured chordae tendinae. The Doppler mode showed 73 cases of MI, 26 of which were at least moderately severe. These cases of MI were commonly excentric jets behind the posterior leaflet. There were 47 cases of AI, 10 of which were at least moderately severe. If all cases of moderately severe or mild AI and MI are considered as pathological when associated with suggestive morphological valve changes, the number of cases of carditis increased from 50 without the Doppler mode to over 80 with this mode. Doppler echocardiography validated the Jones criteria in 16 children. The authors propose Doppler echocardiography criteria for the validation of carditis.