[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.

Use of ADAM-C and CHA2DS2-VASc scores to predict complex aortic atheroma after brain ischemia: A prospective observational study.

BACKGROUND AND AIMS: Complex aortic atheroma (CAA) is a common cause of acute brain ischemia (BI), including ischemic stroke (IS) and transient ischemic attack (TIA), and is associated with recurrence. The CHA2DS2-VASc score is a useful tool for predicting stroke in patients with atrial fibrillation (AF), and can also predict cardiovascular events in other populations, including non-AF populations. The ADAM-C score is a new risk score for predicting the diagnostic yield of transesophageal echocardiography (TEE) after BI. We aimed to evaluate the ability of CHA2DS2-VASc and ADAM-C scores to predict CAA after BI. METHODS: This prospective, multicenter, observational study included 1479 patients aged over 18 years who were hospitalized for BI. CAA was defined as the presence of one or more of the following criteria: thrombus, ulcerated plaque, or plaque thickening ≥ 4 mm. RESULTS: CAA was diagnosed in 216 patients (14.6%). CHA2DS2-VASc and ADAM-C scores were significantly higher in the CAA group versus the non-CAA group (P < .0001 for both). The CHA2DS2-VASc and ADAM-C scores appear to be good predictors of CAA (AUC 0.699 [0.635, 0.761] and 0.759 [0.702, 0.814], respectively). The sensitivity, specificity, predictive positive value (PPV), and negative predictive value (NPV) of the scores for detecting CAA were 94%, 22%, 17%, and 96%, respectively, for a CHA2DS2-VASc score < 2, and 90%, 46%, 22%, and 96%, respectively, for an ADAM-C score < 3 CONCLUSIONS: CHA2DS2-VASc and ADAM-C scores are able to predict CAA after BI. CHA2DS2-VASc < 2 and ADAM-C < 3 both have an interesting NPV of 96%.

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.

ADAM-C score: New risk score for predicting diagnostic yield of transesophageal echocardiography after cerebral ischemia.

BACKGROUND AND AIM: The clinical utility of transesophageal echocardiography (TEE) after brain ischemia (BI) remains a matter of debate. We aimed to evaluate the clinical impact of TEE and to build a score that could help physicians to identify which patients should better benefit from TEE. METHODS: This prospective, multicenter, observational study included patients over 18 years old, hospitalized for BI. TEE findings were judged discriminant if the results showed important information leading to major changes in the management of patients. Most patients with patent foramen ovale were excluded. Variables independently associated with a discriminant TEE were used to build the prediction model. RESULTS: Of the entire population (1479 patients), 255 patients (17%) were classified in the discriminant TEE group. Five parameters were selected as predictors of a discriminant TEE. Accordingly, the ADAM-C score could be calculated as follows: Score = 4 (if age ≥60) + 2 (if diabetes) + 2 (if aortic stenosis from any degrees) + 1 (if multi-territory stroke) + 2 (if history of coronary artery disease). At a threshold lower than 3, the sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of detecting discriminant TEE were 88% (95% CI 85-90), 44% (95% CI 41-47), 21% (95% CI 19-27), and 95% (95% CI 94-97), respectively. CONCLUSION: A simple score based on clinical and transthoracic echocardiographic parameters can help physicians to identify patients who might not benefit from TEE. Indeed, a score lower than 3 has an interesting NPV of 95% (95% CI 94-97).

[Drugs cardiotoxicity]. / Complications cardiaques des médicaments.

Thanks to science advances, cancer is no longer synonymous with death. Life expectancy improvement reveals a new problem: cancer treatment toxicity, including cardiovascular complications, responsible for significant morbidity and mortality. Media scandal of drug-induced valvular heart disease did revise the risk-benefit balance of drugs used (often off-label) as anorectics. Today's society uses drugs heavily but does not accept their side effects. Knowledge and information of these complications is essential. Coronary toxicity of some treatments or drugs commonly used must be known.

Impairment of cardiac metabolism and sympathetic innervation after aneurysmal subarachnoid hemorrhage: a nuclear medicine imaging study.

INTRODUCTION: Although aneurysmal subarachnoid hemorrhage (SAH) is often complicated by myocardial injury, whether this neurogenic cardiomyopathy is associated with the modification of cardiac metabolism is unknown. This study sought to explore, by positron emission tomography/computed tomography, the presence of altered cardiac glucose metabolism after SAH. METHODS: During a 16-month period, 30 SAH acute phase patients underwent myocardial (18)F- fluorodesoxyglucose positron emission tomography ((18)F-FDGPET), (99m)Tc-tetrofosmin and (123)I-meta-iodobenzylguanidine ((123)I-mIBG) scintigraphy, respectively, assessing glucose metabolism, cardiac perfusion, and sympathetic innervation. Patients with initial abnormalities were followed monthly for two months for (18)F-FDG, and six months later for (123)I-mIBG. RESULTS: In this SAH population, acute cardiac metabolic disturbance was observed in 83% of patients (n = 25), and sympathetic innervation disturbance affected 90% (n = 27). Myocardial perfusion was normal for all patients. The topography and extent of metabolic defects and innervation abnormalities largely overlapped. Follow-up showed rapid improvement of glucose metabolism in one or two months. Normalization of sympathetic innervation was slower; only 27% of patients (n = 8) exhibited normal (123)I-mIBG scintigraphy after six months. Presence of initial altered cardiac metabolism was not associated with more unfavorable cardiac or neurological outcomes. CONCLUSIONS: These findings support the hypothesis of neurogenic myocardial stunning after SAH. In hemodynamically stable acute phase SAH patients, cardiomyopathy is characterized by diffuse and heterogeneous (18)F-FDG and (123)I-mIBG uptake defect. TRIAL REGISTRATION: Clinicaltrials.gov NCT01218191. Registered 6 October 2010.

B-type natriuretic peptide release and left ventricular filling pressure assessed by echocardiographic study after subarachnoid hemorrhage: a prospective study in non-cardiac patients.

INTRODUCTION: Serum B-type natriuretic peptide (BNP) is frequently elevated after subarachnoid hemorrhage (SAH), but whether this high BNP level is related to transient elevation of left ventricular filling pressure (LVFP) is unknown. However, in patients with preexistent cardiac pathologies, it is impossible to differentiate between BNP elevation caused by chronic cardiac abnormalities and BNP related to acute neurocardiac injury. METHODS: All adult patients with SAH admitted to our intensive care unit were eligible. Patients were excluded for the following reasons: admission >48 hours after aneurysm rupture, pre-existing hypertension, or cardiac disease. Levels of BNP and cardiac troponin Ic were measured daily for 7 days. Echocardiography was performed by a blinded cardiologist on days 1, 2, and 7. Doppler signals from the mitral inflow, tissue Doppler, and the color M-mode-derived flow propagation velocity (FPV) were obtained to assess echo-estimated LVFP. RESULTS: During a 3-year period, sixty-six consecutive patients with SAH were admitted. Thirty one patients were studied. The BNP level was >100 ng/L in 25 patients (80%) during the first 3 days, with a peak on day 2 (median, 126 ng/L) followed by a gradual decrease (median variation days 1 to 7, 70%). All patients had an ejection fraction >50%. Early transmitral velocity/tissue Doppler mitral annular early diastolic velocity was low: 5.4 (+/- 1.5) on day 1, 5.8 (+/- 1.2) on day 2, and 5.1 (+/- 0.9) on day 7. Early transmitral velocity/FPV was also low: 1.27 (+/- 0.4), 1.25 (+/- 0.3), and 1.1 (+/- 0.2) on days 1, 2, and 7, respectively. Cardiac troponin Ic levels ranged from 0 to 3.67 microg/L and were correlated with BNP (r = 0.63, P < 0.01). CONCLUSIONS: BNP rises gradually over two days and return to normal within a week after SAH. Its release is associated with myocardial necrosis, but is unrelated to elevated LVFP assessed by echocardiography.

An implantable loop recorder study of highly symptomatic vasovagal patients: the heart rhythm observed during a spontaneous syncope is identical to the recurrent syncope but not correlated with the head-up tilt test or adenosine triphosphate test.

OBJECTIVES: The aim of this study was to analyze the heart rhythm during spontaneous vasovagal syncope (VVS) in highly symptomatic patients with implantable loop recorders (ILR) and to correlate this rhythm with the heart rhythm observed during head-up tilt test (HUT). BACKGROUND: Heart rhythm obtained during provocative condition is often used to guide therapy in VVS. To date there is no conclusive evidence that the heart rhythm observed during a positive HUT can predict heart rhythm during VVS or that the heart rhythm observed during a spontaneous syncope will be identical to the recurrent syncope. METHODS: Twenty-five consecutive VVS patients (age 60.2 +/- 17.1 years; 14 women,) presenting with frequent syncopes (6.9 +/- 4.6 episodes/year) and a positive HUT (cardioinhibitory in 8 patients) were implanted with an ILR. Seven of them also had a positive adenosine triphosphate (ATP) test. RESULTS: Follow-up was 17.0 +/- 3.6 months. Thirty VVS were observed in 12 patients. Nine episodes showed bradycardia of <40 beats/min or asystole; progressive sinus bradycardia preceding sinus arrest was the most frequent electrocardiographic finding. Twenty-one syncopes occurred without severe bradycardia. The heart rhythm observed during the first syncope was identical to the recurrence. No correlation was found between slow heart rate at the ILR interrogation and a cardioinhibitory HUT response (p = 1.0) or a positive ATP test (p = 1.0). CONCLUSIONS: In highly symptomatic patients with VVS, the heart rhythm observed during spontaneous syncope does not correlate with the HUT. The heart rhythm during the first spontaneous syncope is identical to the recurrent syncope.

Diastolic asynchrony is more frequent than systolic asynchrony in dilated cardiomyopathy and is less improved by cardiac resynchronization therapy.

OBJECTIVES: To compare the incidence of diastolic and systolic asynchrony, assessed by tissue Doppler imaging (TDI), in patients with congestive heart failure (CHF) and severe left ventricular (LV) dysfunction, and to assess TDI changes induced by cardiac resynchronization therapy (CRT). BACKGROUND: Thirty percent of CRT candidates are nonresponders. Besides QRS width, the presence of echographic systolic asynchrony has been used to identify future responders. Little is known about diastolic asynchrony and its change after CRT. METHODS: Tissue Doppler imaging was performed in 116 CHF patients (LV ejection fraction 26 +/- 8%). Systolic and diastolic asynchrony was calculated using TDI recordings of right ventricular and LV walls. RESULTS: The CHF group consisted of 116 patients. Diastolic asynchrony was more frequent than systolic, concerning both intraventricular (58% vs. 47%; p = 0.0004) and interventricular (72 vs. 45%; p < 0.0001) asynchrony. Systolic and diastolic asynchrony were both present in 41% patients, but one-third had isolated diastolic asynchrony. Although diastolic delays increased with QRS duration, 42% patients with narrow QRS presented with diastolic asynchrony. Conversely, 27% patients with large QRS had no diastolic asynchrony. Forty-two patients underwent CRT. Incidence of systolic intraventricular asynchrony decreased from 71% to 33% after CRT (p < 0.0001), but diastolic asynchrony decreased only from 81% to 55% (p < 0.0002). Cardiac resynchronization therapy induced new diastolic asynchrony in eight patients. CONCLUSIONS: Diastolic asynchrony is weakly correlated with QRS duration, is more frequent than systolic asynchrony, and may be observed alone. Diastolic asynchrony is less improved by CRT than systolic. Persistent diastolic asynchrony may explain some cases of lack of improvement after CRT despite good systolic resynchronization.

Low molecular weight heparins: a guide to their optimum use in pregnancy.

The incidence of pulmonary embolism (PE) and venous thromboembolism (VTE) is higher in pregnant patients than in non-pregnant patients. The incidence of thrombosis in all pregnancies is reported to be between 0.05 and 1%, and an incidence as high as 3% may be present in women after caesarean section. Anticoagulant medication is prescribed during pregnancy in patients presenting with VTE, thrombophilia abnormalities, or a history of PE or VTE. Since unfractionated heparin (UH) does not cross the placental barrier, it has become the gold standard anticoagulant therapy during pregnancy. Oral anticoagulants may also be prescribed during the second trimester but they cross the placental barrier. Low molecular weight heparins (LMWH) are effective, easy to use and have good safety profiles. The practical conditions of use have yet to be validated for pregnancy settings. In the absence of an approved indication, LMWH use during pregnancy is therefore the responsibility of the practitioner. However, several studies on LMWH as prophylaxis for PE or VTE have shown that such products are effective with good safety. Moreover, LMWH use is associated with reduced frequencies of thrombocytopenia and osteoporosis compared with UH use. Very few studies on LMWH use for the treatment of PE or VTE during pregnancy have been published, but the safety of LMWH use in this setting appears to be good. The review of the use of LMWH in pregnancy settings includes recommendations on the practical conditions of use. In the absence of large-scale, randomised, double-blind trials in such settings (which are needed), we propose the use of LMWH as prophylaxis for PE and VTE during pregnancy, but not for the treatment of these conditions. In prophylaxis settings, dalteparin sodium and enoxaparin sodium have been the most widely studied LMWH and we believe that priority should therefore be given to those products. Pending approval of LMWH for use in pregnancy, the use of LMWH off-label is the practitioner's responsibility.