[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.

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.

Prospective, large-scale multicenter trial for the use of drug-coated balloons in coronary lesions: The DCB-only All-Comers Registry.

OBJECTIVES: This prospective, observational all-comers registry assessed the safety and efficacy of a Drug Coated Balloon-only strategy (DCB-only) in patients with coronary lesions. BACKGROUND: Data regarding the performance of a DCB-only approach, especially in patients with previously untreated de-novo coronary artery disease (CAD), are still limited. METHODS: This study was conducted as an international, multicenter registry primarily enrolling patients with de-novo CAD. However, it was also possible to include patients with in-stent restenosis (ISR). The primary endpoint was the rate of clinically driven target lesion revascularization (TLR) after 9 months. RESULTS: A total of 1,025 patients with a mean age of 64.0 ± 11.2 years were enrolled. The majority of treated lesions were de-novo (66.9%), followed by drug-eluting-stent ISR (DES-ISR; 22.6%) and bare-metal-stent ISR (BMS-ISR; 10.5%). The TLR rate was lower in the de-novo group (2.3%) when compared to BMS- (2.9%) and DES-ISR (5.8%) (P = 0.049). Regarding MACE, there was a trend toward fewer events in the de-novo group (5.6%) than in the BMS- (7.8%) and DES-ISR cohort (9.6%) (P = 0.131). Subgroup analyses revealed that lesion type (95% CI 1.127-6.587); P = 0.026) and additional stent implantation (95% CI 0.054-0.464; P = 0.001) were associated with higher TLR rates. CONCLUSIONS: Our results show that DCB-only angioplasty of de-novo coronary lesions is associated with low MACE and TLR rates. Thus, DCBs appear to be an attractive alternative for the interventional, stentless treatment of suitable de-novo coronary lesions.

Cardiovascular Mechanisms of Extravascular Lung Water Accumulation in Divers.

This study assessed the relation between altered cardiac function and the development of interstitial pulmonary edema in scuba divers. Fifteen healthy men performed a 30-minute scuba dive in open sea. They were instructed to fin for 30 minutes and were wearing wet suits. Before and immediately after immersion, cardiac indexes and extravascular lung water were measured using echocardiography and lung ultrasound, respectively. The mean ultrasound lung comet score increased from 0 to 4.6 ± 3.4. The diameter of the inferior caval vein increased by 47 ± 5.2%, systolic pulmonary artery pressure by 105 ± 8.6%, left atrial volume by 18.0 ± 3.3%, and left ventricle end-diastolic volume by 10 ± 2.4% suggesting that both right and left ventricular (LV) filling pressures were elevated. Doppler studies showed an increased mitral E peak (+2.5 ± 0.3%) and E/A ratio (+22.5 ± 3.4%) with a decreased mitral A peak (-16.4 ± 2.7%), E peak deceleration time (-14.5 ± 2.4%) consistent with rapid early LV filling but without a change in LV stroke volume. There was an increase in right/left ventricle diameter ratio (+33.6 ± 4.8%) suggesting a relative increase in right-sided heart output compared with the left. Furthermore, the lung comet score correlated significantly with inferior caval vein diameter, systolic pulmonary artery pressure, right/left ventricle diameter ratio, and E-wave deceleration time. In conclusion, the altered right/left heart stroke volume balance could play an essential role in the development of immersion pulmonary edema. Our findings have important implications for the pathogenesis of cardiogenic pulmonary edema.

[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.

Transradial approach and subclavian wired temporary pacemaker to increase safety of alcohol septal ablation for treatment of obstructive hypertrophic cardiomyopathy: the TRASA trial.

BACKGROUND: Alcohol septal ablation (ASA) is a therapeutic catheter-based option and an alternative to surgical myectomy in the treatment of patients with hypertrophic obstructive cardiomyopathy. Although the safety of the ASA procedure has been consistently improved, a temporary transvenous pacemaker is recommended for at least 48h postprocedure, with several drawbacks, including the risk of cardiac perforation and infection, and the absence of any fixation mechanism. In addition, femoral artery catheterization has resulted in a concomitant increase in bleedings and iatrogenic femoral artery injuries. AIMS: To evaluate and validate the feasibility of less invasive management of ASA using the transradial approach and a subclavian wired temporary pacemaker. METHODS: To avoid transfemoral temporary pacing, we used a subclavian bipolar active-fixation permanent pacing lead, stitched to the skin and connected to a desterilized recuperation pacemaker. The day before discharge, if there was no high-degree atrioventricular block, the pacemaker lead was removed. In all patients, we used the right radial access and the left main was cannulated with a 6F Judkins left 3.5 guiding catheter. RESULTS: Thirty consecutive patients were prospectively and successfully included in our study. No complication was observed during the hospital stay, neither access-site nor stimulation-lead related. CONCLUSIONS: Our study shows the feasibility and safety of a transradial approach and a subclavian wired temporary pacemaker. The reduction in periprocedural complications offered by this strategy reflects the less invasive nature of ASA, without increasing the cost and complexity of the procedure.

An unusual "winter case" of myocarditis.

Myocardial injury from moderate to severe carbon monoxide (CO) poisoning is common. We reported a case of acute myocarditis related to CO poisoning in a 34 year-old man confirmed by normal coronary angiography, diffuse sub-epicardial late enhancement at MRI and COHb level of 25%.The patient was treated with hyperbaric oxygen therapy with favourable clinical evolution.

Delayed occurrence of complete heart block after ethanol septal ablation for hypertrophic obstructive cardiomyopathy.

Ethanol septal ablation has emerged as a less invasive alternative to surgical myomectomy for treatment of hypertrophic obstructive cardiomyopathy (HOCM). The procedure has very low mortality, but complete heart block (CHB) is a common complication. Prior studies suggested existence of baseline characteristics, ECG features and procedural risk factors, which are highly predictor of CHB requiring permanent pacemaker after ethanol septal ablation. CHB is often preceded by postprocedure conduction abnormalities and generally develops within 48 h after ethanol ablation. We present a unique case of a patient with HOCM who developed a CHB on 8th day postprocedure without preceding conduction abnormalities or other classic risk factors.

Index of Microcirculatory Resistance: a new effective invasive tool to assess reperfusion after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.

Assessment of myocardial reperfusion during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction remains challenging. The pressure wire-derived Index of Microcirculatory Resistance (IMR) is a parameter reflecting the microcirculation status. We illustrated with two cases the accuracy of the IMR in the setting of STEMI to predict myocardial damage as well as LV function recovery.

Clopidogrel response: head-to-head comparison of different platelet assays to identify clopidogrel non responder patients after coronary stenting.

OBJECTIVES: We investigated the agreement between different platelet tests to identify clopidogrel non response. BACKGROUND: Biological definition of clopidogrel non response remains controversial. Different platelet tests have been linked with recurrent ischemic events and proposed for daily practice. METHODS: We prospectively investigated the agreement of platelet tests to isolate clopidogrel non response in patients receiving high 150 mg clopidogrel maintenance dose after coronary stenting. Clopidogrel response was assessed with ADP-induced aggregation (ADP-Ag) (non response if >70%), Platelet reactivity index VASP (PRI VASP) (non response if >50%) and Verify Now Point-of-care assay (VN) (non response if PRU > 240 AU). RESULTS: Seventy consecutive patients were included. The rates of non-responders were respectively: 13% (n = 9) with the ADP-Ag, 39% (n = 27) with the PRI VASP and 33% (n = 23) with the VN. We observed significant correlation between different platelet tests assessing clopidogrel response: r = 0.55 (p < 0.0001) for ADP-Ag and PRI VASP, r = 0.64 (p < 0.0001) for ADP-Ag and VN and r = 0.59 (p < 0.0001) for PRI VASP and VN. However, using the most common thresholds, the agreement between the difference tests was poor: 0.35 for ADP-Ag and PRI VASP, 0.36 for ADP-Ag and VN and 0.46 for PRI VASP and VN. CONCLUSION: This study showed that assessment of platelet function inhibition by clopidogrel is highly test-specific. Indeed, our results demonstrated a poor agreement between different platelet assays and suggested that identification of clopidogrel non responders is test-dependent.

Coronary wall characteristics after myocardial infarction without significant coronary angiographic lesion: an intravascular ultrasound study.

AIM: Coronary of angiography may be normal or without significant lesion after myocardial infarction (MI) in about 10% of cases. Our aim was to evaluate intravascular ultrasound (IVUS) findings, mainly remodelling, in patients with normal or near normal angiography early after MI. METHODS AND RESULTS: We prospectively included 17 patients, admitted for STEMI or non-STEMI with no lesion > 30% (QCA) on early coronary angiography. Culprit vessel was defined by evidence of a thrombus in a proximal segment, distal embolization or focal akinesia of the left ventricle. Negative remodelling (NR) was defined as a remodelling index (lesion/reference external elastic membrane cross sectional area [CSA]) < 0.95, no remodelling as between 0.95-1.05, and positive remodelling (PR) as > 1.05. IVUS could identify a short, single, minor, eccentric and hypoechogenic lesion in all patients, of proximal location in 76.4% cases. PR was observed in only 1 patient (5.9%). CONCLUSION: A discrete lesion was observed in all patients with apparently normal arteries. Although previous reports have shown an association between PR and vulnerability, in our study PR was unusual. Our study supports the hypothesis that in some patients, vulnerability may appear very early in the natural history of coronary artery disease before any vessel remodelling.

Predictive values of post-treatment adenosine diphosphate-induced aggregation and vasodilator-stimulated phosphoprotein index for stent thrombosis after acute coronary syndrome in clopidogrel-treated patients.

A low response to clopidogrel has been associated with an increased risk of stent thrombosis. However, the definition of a nonresponse to clopidogrel remains controversial, and different tests have been used to assess the clopidogrel response. The present study was designed to assess the predictive value of adenosine diphosphate (ADP)-induced platelet aggregation (ADP-Ag) and the Platelet Reactivity Index of vasodilator-stimulated phosphoprotein for the occurrence of stent thrombosis in patients admitted for non-ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention. A total of 598 consecutive patients with non-ST-elevation acute coronary syndrome undergoing coronary stenting were prospectively included. They received 600 mg of clopidogrel >or=12 hours before percutaneous coronary intervention. Acute or subacute definite or probable stent thrombosis occurred in 11 patients (1.8%). These patients had significantly greater ADP-Ag compared to patients free of stent thrombosis (68 +/- 14% vs 56 +/- 19%, p = 0.002) but only a trend toward a greater Platelet Reactivity Index of vasodilator-stimulated phosphoprotein (62 +/- 14% vs 53 +/- 23%, p = 0.19). The construction of receiver operating characteristic curves to examine the most predictive value of ADP-Ag for stent thrombosis gave a threshold of ADP-Ag of >67% to identify low responders. These patients were at a greater risk of stent thrombosis than the clopidogrel responders (4.3% vs 0.8%, odds ratio 5.8, 95% confidence interval 1.9 to 24.6, p = 0.003). In conclusion, in patients with non-ST-elevation acute coronary syndrome undergoing percutaneous coronary intervention, ADP-Ag is a good parameter to identify clopidogrel nonresponders who are at increased risk of stent thrombosis, with a cutoff value of ADP-Ag of >67%.

Predictive value of post-treatment platelet reactivity for occurrence of post-discharge bleeding after non-ST elevation acute coronary syndrome. Shifting from antiplatelet resistance to bleeding risk assessment?

AIMS: We assessed prospectively the association between occurrence of post-discharge non-CABG-related TIMI major and minor bleeding and post-treatment platelet reactivity in patients with non-ST elevation acute coronary syndrome (NSTE ACS). METHODS AND RESULTS: Five hundred and ninety-seven consecutive patients admitted with NSTE ACS were prospectively included. Between hospital discharge and one month follow-up, we observed 16 (2.7%) non-CABG-related TIMI haemorrhagic complications including five (0.84%) major and 11 (1.8%) minor bleeds. Patients with bleeding had significantly lower post-treatment values of ADP-induced aggregation (43+/-14% versus. 56+/-19%, p=0.002) and platelet reactivity index VASP (43+/-14% versus 54+/-23%; p=0.04) and a trend for lower values of arachidonic acid-induced aggregation (2.4+/-5.4 versus 13+/-21; p=0.27). After stratification by quartiles based on post-treatment ADP-induced platelet aggregation, we identified patients in the first quartile as hyper-responders with very low post-treatment platelet reactivity, below <40%. The risk of TIMI major and minor bleeding was significantly higher in the first quartile of hyper-responders than in the others quartiles: 10 (6.6%) versus six (1.4%), p=0.001. CONCLUSIONS: Our results suggest that assessment of post-treatment platelet reactivity might be used to detect hyper-responders to antiplatelet therapy with higher risk of non-CABG related bleeding and tailor antiplatelet therapy according to both ischaemic and bleeding risk.

Comparison of omeprazole and pantoprazole influence on a high 150-mg clopidogrel maintenance dose the PACA (Proton Pump Inhibitors And Clopidogrel Association) prospective randomized study.

OBJECTIVES: This study sought to compare the effect of 2 proton pump inhibitors (PPIs) on platelet response to clopidogrel after coronary stenting for non-ST-segment elevation acute coronary syndrome (NSTE ACS). BACKGROUND: Use of omeprazole has been reported to significantly decrease the clopidogrel antiplatelet effect because of cytochrome P450 interaction. Because all PPIs are metabolized by CYP2C19, but to a varying degree, we hypothesized that the reported negative omeprazole-clopidogrel drug interaction may not be caused by a class effect. METHODS: A total of 104 patients undergoing coronary stenting for NSTE ACS were prospectively included and randomized to omeprazole or pantoprazole 20 mg. They received at discharge 75-mg aspirin and 150-mg clopidogrel. Platelet reactivity index (PRI) vasoactive stimulated phosphoprotein (VASP) was used to assess clopidogrel response and adenosine diphosphate (ADP)-induced aggregation for platelet reactivity (ADP-Ag). RESULTS: After 1 month, patients receiving pantoprazole had a significantly better platelet response to clopidogrel as assessed with the PRI VASP: 36 +/- 20% versus 48 +/- 17% (p = 0.007). We identified more clopidogrel nonresponders in the omeprazole group than in the pantoprazole group: 44% versus 23% (p = 0.04), odds ratio: 2.6 (95% confidence interval: 1.2 to 6.2). Conversely, we did not observe any significant difference in platelet reactivity with ADP-Ag between the omeprazole and pantoprazole groups: 52 +/- 15% and 50 +/- 18%, respectively (p = 0.29). CONCLUSIONS: The present findings suggest the preferential use of pantoprazole compared with omeprazole in patients receiving clopidogrel to avoid any potential negative interaction with CYP2C19.

Aspirin noncompliance is the major cause of "aspirin resistance" in patients undergoing coronary stenting.

OBJECTIVES: We investigated the hypothesis that biological aspirin "resistance" may often be related to noncompliance in patients undergoing coronary stenting. BACKGROUND: Premature discontinuation of antiplatelet therapy has been identified as a major risk factor for stent thrombosis and prior aspirin withdrawal has been associated with poor prognosis after acute coronary syndrome. METHODS: We prospectively investigated the occurrence of aspirin noncompliance in 136 consecutive patients undergoing coronary stenting receiving aspirin 75 mg daily. We analyzed posttreatment maximal intensity of arachidonic acid-induced platelet aggregation (AA-Ag) during hospitalization after controlled intake of aspirin and 1 month after hospital discharge. After 1 month, all "nonresponders" received controlled aspirin 75 mg and assessment of response was repeated. Aspirin nonresponse was defined by AA-Ag >30%. RESULTS: During inhospital period, the range of AA-Ag varied from 0% to 34% with a mean value of 7.5% +/- 10%, and 4 patients (3%) were classified as nonresponders. One month after discharge, AA-Ag of the population was significantly higher than during the hospital phase (15.3 +/- 23 vs 7.5 +/- 10%, P = .0004), and 19 patients (14%) were identified as nonresponders. After controlled administration of aspirin, all but one of these nonresponders became responders and were identified as patients with noncompliance rather than biological resistance. CONCLUSION: Aspirin resistance is rare in compliant patients using methods that directly indicate the degree of platelet cyclooxygenase inhibition. More than 10% of patients receiving aspirin for coronary stenting are noncompliant for aspirin therapy during the first month after stenting. These results suggest a need for improved education of these patients.

Catheter related venous thrombosis with cooling and warming catheters: two case reports.

INTRODUCTION: Intravascular cooling and warming catheters are among a range of proliferating technologies used for temperature control. Complications related to the use of these devices are few, and no definitive evidence has been presented thus far to indicate any differences in complication rates between these balloon catheters and other central vein catheters. We report two cases of cooling and warming catheter-related venous thrombosis. They are the both first ones report of this kind in the literature. CASE PRESENTATION: The first case was a 17-year-old man admitted with severe head trauma. On day 6, he presented with severe intracranial hypertension, requiring increased medical treatment: mannitol osmotherapy, barbiturate-induced coma, and mild therapeutic hypothermia. A double-lumen Alsius CoolLine catheter was placed in the inferior veina cava via the left femoral vein and active cooling was begun. On day 10, physical examination of the left inguinal area and echo-doppler revealed catheter-related thrombophlebitis with left iliocaval vein occlusion. The second case was a 42-year-old man admitted with a severe burn. On day 2, the patient was taken to the operating room for the first staged excision of his burn wounds. A triple lumen Alsius Icy catheter was placed in the inferior vena cava via the right femoral vein and active core warming of the patient was begun. From day 2 to day 7, active core warming of the patient was maintained. On day 7, he presented with a septic thrombophlebitis. Echo-doppler revealed a 4-cm-long thrombus at the femoral catheter site with complete blood flow obstruction and blood cultures and catheter tip were positive for methicillin-resistant Staphylococcus aureus. CONCLUSION: Although generally considered safe, cooling and warming catheters can be associated with mechanical complications such as catheter-related venous thrombosis. Intensivists who use these devices should be aware of this possible complication. Finally, as with any other invasive catheter, to reduce the risk of complications, the catheter should be removed promptly when no longer needed.