[Acute dissection of the thoracic aorta. Symptoms and complications]. / Dissection aiguë de l'aorte thoracique. Symptômes et complications.

Acute dissection of the aorta is an increasingly recognised pathology, the diagnosis of which is sometimes delayed despite the fact that advances in medical imaging provide almost perfect diagnostic accuracy. Some of the symptoms are particularly suggestive. Chest pain is the key symptom, and the greater the intensity, usually described as a migratory intrathoracic tearing sensation irradiating towards the lumbar region. The other symptoms become meaningful in association with this pain: paraplegia, acute peripheral ischaemia, hemiplegia. Clinical examination is capital when a diastolic murmur of aortic regurgitation is heard or when a distal pulse is absent, the blood pressure is asymmetric or a pericardial rub is detected. The frighteningly poor initial prognosis of acute dissection of the aorta has been transformed by surgery, providing, that it is performed early. Optimal therapeutic results can only be obtained by and early diagnosis.

Evaluation of the effect of phosphodiesterase inhibitors on mortality in chronic heart failure patients. A meta-analysis.

We examined the influence of phosphodiesterase inhibitors (PDIs) on mortality in patients with overt chronic heart failure. A total of 13 randomised, placebo-controlled trials of PDIs involving 2808 patients were selected. Meta-analysis, using data for all patients, showed that there was a non-significant (P = 0.16) increase of about 17% in the mortality rate of patients receiving a PDI [odds ratio (OR) 1.17, 95% confidence interval (CI) 0.94-1.46]. However, the observed treatment effects were found to be heterogeneous due to the results from the trials on vesnarinone. The heterogeneity became non-significant (P = 0.77) when these trials were removed, and a significant increase in the mortality rate was observed under treatment with the other PDIs (OR 1.41, 95% CI 1.11-1.79). In the subgroups of patients with or without additional vasodilator (VD) treatment, similar results were observed (PDI with VD: OR 1.3, 95% CI 1.03-1.7; PDI without VD: OR 2.04, 95% CI 1.1-3.8). These results indicate that PDIs (with the exception of vesnarinone) should not be prescribed for long-term use in patients with overt chronic heart failure. Additional vasodilator treatment in patients receiving PDIs for chronic heart failure does not explain the increased mortality seen with PDIs. This toxicity must, therefore, arise by other mechanisms. Further experimental and clinical evaluation is needed to confirm the beneficial influence of vesnarinone on survival in chronic heart failure patients and to identify the mechanism(s) differentiating this agent's therapeutic effect from that of other PDIs.

The role of an initial single-blind placebo period in phase I clinical trials.

The effect of an initial single-blind placebo period in a phase I clinical trial was assessed in 12 volunteers who underwent five weekly treatment periods, consisting of treatment on the first day and a six-day wash-out period. An initial single-blind placebo period was followed by three different single doses of a platelet-aggregation factor inhibitor and another placebo period, under a double-blind Latin square design. Reports of abnormal symptoms were collected using a questionnaire designed by our group. A total of 13 abnormal symptoms were reported during the first period and only nine for the following four periods, indicating a clear placebo period effect. These preliminary results suggest that an initial single-blind period may be usefully included in phase I clinical trials.

Electrophysiologic effects of a potassium channel activator (pinacidil) on repolarization parameters in healthy volunteers: a surface ECG study.

About a quarter to a third of patients receiving pinacidil, a new cyanoguanidine vasodilator, show ECG changes, in particular T-wave modifications that sometimes mimic myocardial ischemia. To investigate these changes, we performed a randomized placebo-controlled trial in 10 carefully selected, healthy subjects who received single oral doses of either pinacidil (25 mg), quinidine (330 mg), and placebo. Quinidine, which induces specific modifications to the surface ECG signal, was used as an internal control. The complete experimental design involved five consecutive administrations of the drugs in random order: pinacidil (twice), quinidine (twice), and placebo (once), separated by a week-long washout period. Electrophysiologic data acquisition and signal analysis were performed with the Lyon vectocardiographic processing system. Pinacidil decreased T-wave amplitude (-0.26 +/- 0.1 mV) significantly as compared with placebo (-0.14 +/- 0.06 mV), but did not change the duration of the T-wave. Although the cardiac rate increased with pinacidil, the QTc interval remained constant. Conversely, quinidine did not modify the RR interval but significantly increased duration of the T-wave (+67 +/- 20 ms) and QTc interval (+53 +/- 13 ms) as compared with placebo (+17 +/- 13 and +18 +/- 11 ms). In addition, no specific ischemic changes to the T-loop were observed with pinacidil. The modifications to the surface ECG signal caused by pinacidil appear to be drug-specific and related to its electrophysiologic properties rather than involving any ischemic mechanism. Such an approach may be useful for describing morphologic ECG changes caused by new drugs and identifying possible underlying electrophysiologic mechanism(s), which should then be confirmed in further studies.