High prevalence of ventricular repolarization abnormalities in people carrying TGFßR2 mutations.

Mutations in the TGFßR2 gene have been associated with a life threatening risk of aortic dissection but no arrhythmic death has been previously reported. Two young females carrying a TGFßR2 mutation, initially diagnosed as Marfan syndrome or Loeys Dietz syndrome, presented sudden death with autopsy ruling out dissection. The ECGs of the 2 Sudden Cardiac Deaths revealed profound ventricular repolarization abnormalities with a sinusoidal T-U morphology associated with normal left ventricular ejection fraction. These data strongly suggest sudden cardiac arrhythmic deaths and prompted us to systematically study the repolarization pattern in the patients with TGFßR2 mutations. ECG findings from 58 mutation carriers patients (TGFßR2 group) were compared with those of 46 non-affected first degree relatives (control group). TGFßR2 mutation was associated with ventricular repolarization abnormalities in 47% of patients (p < 0.001 vs. controls), including a 19.6 ms (95%CI 8.7; 30.5) QTc interval prolongation compared to the non-affected first degree relatives (p < 0.001), higher prevalence of abnormal U waves (16% vs. 2%), and sinusoidal T-U morphology (10% vs. 0%). TGFßR2 mutations can be associated with abnormal ventricular repolarization pattern, longer QT interval than non-carrier relatives and an increased risk for sudden death.

Eclipsed mitral regurgitation: an unusual cause of acute heart failure.

AIMS: So far, a total of five patients with eclipsed mitral regurgitation (MR) have been reported in the literature by three different teams. The aim of this article was to detail clinical and echocardiographic characteristics, and outcome of patients presenting eclipsed MR. METHODS AND RESULTS: We defined eclipsed MR as spontaneous appearance, at rest, from 1 min to the next of an acute restriction in the motion of mitral leaflets preventing coaptation and leading to massive MR in patients with normal left ventricular end-diastolic diameter, left ventricular ejection fraction >45%, and baseline MR ≤2. Spontaneous regression occurred within 30 min, and no obvious trigger such as acute hypertension, new-onset arrhythmia, or myocardial ischaemia is present. Clinical data, ECG, echocardiographic data, surgery report, and follow-up status of six patients with eclipsed MR are reported: all were post-menopausal women with median age of 74 [57-80] years presenting hypertension (4/6), chronic kidney disease (5/6), or chronic anaemia (4/6). Five out of six patients experienced acute pulmonary oedema requiring hospitalization and underwent mitral valve replacement because of heart failure recurrence. Two patients died in the first days after surgery while the three others are free of symptoms at, respectively, 56, 18, and 10 months follow-up. CONCLUSION: Eclipsed MR is a clinical and echocardiographic syndrome responsible for heart failure with preserved EF. It is presently underdiagnosed and should be evoked in cases of recurrent acute pulmonary oedema without obvious trigger, in particular in patients presenting discordant evaluation of MR severity over time.

[Pulmonary hypertension and heart failure: the role of pulmonary vasculature]. / Hypertension pulmonaire et insuffisance cardiaque : le rôle de la vascularisation pulmonaire.

Left heart disease is the most common cause of pulmonary hypertension. Increased left-sided filling pressure leads to passive postcapillary venous hypertension. In some patients, pulmonary vasoconstriction and vascular remodeling may lead to a further increase in pulmonary pressure. When precapillary hypertension component is associated to left heart failure, the elevation of pulmonary pressure is out of proportion with left atrial pressure: transpulmonary gradient greater than 12 mmHg (mean pulmonary pressure -- mean capillary pressure) and pulmonary vascular resistance greater than three Wood units. Precapillary pulmonary hypertension is common in severe systolic heart failure. Before cardiac transplantation, increased pulmonary vascular resistance greater than 3,5 Wood units are reported in 19 to 35% of patients. In those patients vasoreactivity tests are performed with inotropic and/or systemic and/or pulmonary agents to determine the risk of right heart failure after transplantation. There is no pulmonary vascular resistance level above which transplantation is contraindicated. Cardiac assistance may be used before and after transplantation when pulmonary hypertension is severe and not reversible with conventional treatment and/or pulmonary vasodilators. The contribution of precapillary PH in diastolic heart failure is not known but can be significant and lead to disproportionate PH particularly in elderly. The precapillary component of pulmonary hypertension could be a therapeutic target for specific pulmonary vasodilators. Until now pharmacological trials has been disappointing and those medications can be dangerous because of increasing blood flow to the pulmonary capillaries with a risk of pulmonary edema when left sided pressure are still elevated.

[Is there an indication for the association of betablockers and angiotensin II receptor antagonists in cardiac failure?]. / Y a-t-il une place pour i'association beta-bloquants/antagonistes des récepteurs à l'angiotensine II dans l'insuffisance cardiaque?

ACE inhibitors initially developed as vasodilators are effective by their anti-hormonal action. Antagonists of the receptors of angiotensin II (ARA II) should provide an equivalent or better blockade of the rennin-angiotensin system (absence of tolerance). Clinical trials have shown equivalent haemodynamic effects of the two classes, equal functional tolerance but mortality studies have shown more variable results. None have shown the superiority of ARA II over ACE inhibitors and the demonstration of their equivalence has just been reported with high doses in the post-infarction period. A deleterious effect of ARA II in association with betablockers was reported in two mortality studies but has not been confirmed in the most recent trials. The difficulty is to determine the roles of the association of ARA II-ACE inhibitors, ARA II-antialdosterones or of the association of all three classes of molecules.

[Marfan syndrome]. / Syndrome de Marfan.

Marfan's syndrome is a monogenetic disease with an autosomal dominant transmission generally accompanied by type I fibrillin abnormality. This widely-distributed molecule participates in the structure of connective tissues so that any aberration may result in disease of many systems: skeletal morphology, dislocation of the lens, neurological or cutaneous signs and dilatation of the aorta predisposing to dissection, mitral valve prolapse being a common association. The diagnosis, clinical because of the size of the culprit gene and the multiplicity of the possible mutations, is sometimes difficult, and diagnostic criteria have been proposed. It is important to make the diagnosis because treatment is based on the restriction of violent exercise, betablocker therapy and regular echocardiographic monitoring of the ascending aorta, the region at highest risk of dilatation and dissection. A family enquiry is essential to make the diagnosis before the onset of complications in pauci-symptomatic patients (great intra-familial variability). Pregnancy poses special problems in these patients.

[A new cause of increased troponin levels: junctional tachycardia]. / Une nouvelle cause d'élévation de la troponine: la tachycardie jonctionnelle.

The authors report 4 cases of acute coronary syndromes with increased troponine levels during junctional tachycardia in patients with angiographically normal coronary arteries. ST segment changes during junctional tachycardia have no predictive value for the detection of coronary artery disease. Increased troponine, a marker of myocardial cellular necrosis, is not a sign of coronary lesions. A disequilibrium between the increased metabolic and energetic requirements of the myocardium and decreased perfusion due to the tachycardia could explain this observation. The recommended management of these patients is not to perform coronary angiography initially in the absence of cerebrovascular risk factors, but rather to document myocardial ischaemia by a non-invasive method such as echocardiography or scintigraphy.

[Myasthenia in the aged: a case with unusually late onset]. / Myasthénie du sujet âgé. Un cas de révélation particulièrement tardive.

BACKGROUND: Myasthenia is an uncommon autoimmune condition that can occur at any age. Peak frequency is seen around the age of 65 years. We report a case with a particularly late onset and discuss the particular conditions of myasthenia in the elderly subject. CASE REPORT: A 97-year-old patient was hospitalized for dysphonia and dysphagia associated with exercise-induced dyspnea. The general picture suggested generalized myasthenia confirmed by the electromyography exploration and a positive anticholinesterase test. Treatment with acetylcholinesterase inhibitor was effective although cure was incomplete. Further improvement was obtained with immunosuppressor therapy using azathioprine. DISCUSSION: The clinical presentation of very late onset myasthenia differs little from that in younger subjects excepting the very high frequency of brain stem involvement in the initial presentation. Diagnosis may however be more difficult as other conditions are more easily taken to be the causal element. Thus, for the elderly patient, the real problem is to envisage the diagnosis of myasthenia. Positive diagnosis is based on the same criteria as in younger subjects. Clinicians should be aware of the possibility of myasthenia in the geriatric population as specific treatment can improve functional prognosis with satisfactory efficacy.