[Ibrutinib-associated atrial fibrillation : A therapeutic challenge]. / Fibrillation atriale associée à l'ibrutinib : un challenge thérapeutique.

Ibrutinib is a potent Bruton tyrosine kinase inhibitor and is an effective and well-tolerated treatment for a variety of lymphoid diseases. However, its use is associated with an increased incidence of atrial fibrillation ranging from 4% to 16%. New onset atrial fibrillation in cancer patients is associated with a significantly higher risk of heart failure and thromboembolism, even after adjusting for known risk factors. Ibrutinib also inhibits platelet activation and decisions regarding anticoagulation must be carefully weighed against this increased risk of bleeding. It is well-known that the anti-arrhythmic and antithrombotic strategy for atrial fibrillation related to ibrutinib has its own characteristics. Physicians should be familiar with the special management considerations imposed by this drug. Indeed, the co-prescription of therapy in combination with ibrutinib must be carefully weighed in view of its numerous drug interactions. We review the potential mechanisms and incidence of ibrutinib-associated atrial fibrillation.

Diuretic vs. placebo in intermediate-risk acute pulmonary embolism: a randomized clinical trial.

AIMS: The role of diuretics in patients with intermediate-risk pulmonary embolism (PE) is controversial. In this multicentre, double-blind trial, we randomly assigned normotensive patients with intermediate-risk PE to receive either a single 80 mg bolus of furosemide or a placebo. METHODS AND RESULTS: Eligible patients had at least a simplified PE Severity Index (sPESI) ≥1 with right ventricular dysfunction. The primary efficacy endpoint assessed 24 h after randomization included (i) absence of oligo-anuria and (ii) normalization of all sPESI items. Safety outcomes were worsening renal function and major adverse outcomes at 48 hours defined by death, cardiac arrest, mechanical ventilation, or need of catecholamine. A total of 276 patients underwent randomization; 135 were assigned to receive the diuretic, and 141 to receive the placebo. The primary outcome occurred in 68/132 patients (51.5%) in the diuretic and in 49/132 (37.1%) in the placebo group (relative risk = 1.30, 95% confidence interval 1.04-1.61; P = 0.021). Major adverse outcome at 48 h occurred in 1 (0.8%) patients in the diuretic group and 4 patients (2.9%) in the placebo group (P = 0.19). Increase in serum creatinine level was greater in diuretic than placebo group [+4 µM/L (-2; 14) vs. -1 µM/L (-11; 6), P < 0.001]. CONCLUSION: In normotensive patients with intermediate-risk PE, a single bolus of furosemide improved the primary efficacy outcome at 24 h and maintained stable renal function. In the furosemide group, urine output increased, without a demonstrable improvement in heart rate, systolic blood pressure, or arterial oxygenation.ClinicalTrials.gov identifier NCT02268903.

Epidemiological, clinical, and echocardiographic features of twenty 'Takotsubo-like' reversible myocardial dysfunction cases with normal coronarography following immersion pulmonary oedema.

BACKGROUND: Pulmonary immersion oedema is a frequent diving accident. Although its outcome is generally favourable within 72 h, it can nonetheless lead to heart failure or sudden death. Cases of transient myocardial dysfunction have been reported in the literature. This phenomenon is similar to Takotsubo syndrome in many ways. It is characterised by transient myocardial hypokinesia, without associated coronary lesions. METHODS: We report on 20 cases of patients who showed transient alteration of left ventricular kinetics with normal coronary angiography over the course of an immersion pulmonary oedema. RESULTS: The echocardiographic localisation of the myocardial damage was generally focal and not centred on the apex with an average left ventricular ejection fraction of 45%. The main anomalies in the electrocardiographic repolarisation were T wave inversion with corrected QT interval prolongation. We also observed a moderate increase in troponin levels, with discordance between the enzymatic peak and the severity of the left ventricle segmental dysfunction. CONCLUSION: These cases suggest the incidence of a clinical entity strongly reminiscent of Takotsubo phenomenon of atypical topography as a consequence of diving accidents.

Progression of early repolarization patterns at a four year follow-up in a female flight crew population: Implications for aviation medicine.

BACKGROUND: To assess the prevalence, the appearance, and the distribution, as well as the fluctuation over time of early repolarization patterns after four years in a female population derived from the French aviation sector. METHODS: This was a retrospective longitudinal study from 1998 to 2010 of a population of female employees who received a full clinical examination and an electrocardiogram (ECG) upon their recruitment and after a period of four years. RESULTS: A total of 306 women were included (average of 25.87 ± 3.3 years of age). The prevalence of early repolarization was 9.2%. The most common appearance was J-point slurring for 64.3% (i.e. 20/28 subjects) that occurred in the inferior leads for 28.6% (i.e. 8/28 subjects). After four years, the prevalence was 7.5%, with a regression of this aspect in five of the subjects. There were no changes in the ECG in terms of the distribution and the appearance among the 23 subjects for whom the aspect persisted. Over the course of this four year period all of the subjects remained asymptomatic. CONCLUSIONS: Early repolarization in this largely physically inactive female population was common, and it fluctuated over time. At present, no particular restrictions can be placed on asymptomatic flight crew who exhibit this feature in the absence of a prior medical history for heart disease.

Prevalence of early repolarization patterns in a French military population at low cardiovascular risk: implications for preventive medicine.

BACKGROUND: Early repolarization pattern (ERP) associated with a risk of sudden death has recently been described. Very few studies have examined the prevalence of this pattern in a military population characterized by a predominance of young, active male subjects. Therefore, the main objective of this study was to evaluate the prevalence of ERP in a healthy military population free of heart disease but subjected to extreme and potentially arrhythmogenic physical activity. METHODS: This prospective, multicenter study was carried out from November 2010 to November 2011 and included 746 individuals undergoing ECG screening; 466 were men (62.4%) and 280 were women (37.5%). Each ECG was interpreted twice by trained cardiologists. RESULTS: The total prevalence of ERP was 13.8% (103/746); 16% (46/280) in women and 12% (57/466) in men (P > 0.05). It declined with age and the pattern of slurring in inferior location was the most common. Heart rate was significantly lower in military officers with ERP. CONCLUSIONS: ERP was commonly found in this healthy military population. Preventing the risk of sudden death in this population requires systematic ECG screening, medical history analysis and clinical examination to identify symptomatic patients.