Hélène Bouvaist

Fibrinolysis for patients with intermediate-risk pulmonary embolism

BACKGROUND The role of fibrinolytic therapy in patients with intermediate-risk pulmonary embolism is controversial. METHODS In a randomized, double-blind trial, we compared tenecteplase plus heparin with placebo plus heparin in normotensive patients with intermediate-risk pulmonary embolism. Eligible patients had right ventricular dysfunction on echocardiography or computed tomography, as well as myocardial injury as indicated by a positive test for cardiac troponin I or troponin T. The primary outcome was death or hemodynamic decompensation (or collapse) within 7 days after randomization. The main safety outcomes were major extracranial bleeding and ischemic or hemorrhagic stroke within 7 days after randomization. RESULTS Of 1006 patients who underwent randomization, 1005 were included in the intention-to-treat analysis. Death or hemodynamic decompensation occurred in 13 of 506 patients (2.6%) in the tenecteplase group as compared with 28 of 499 (5.6%) in the placebo group (odds ratio, 0.44; 95% confidence interval, 0.23 to 0.87; P=0.02). Between randomization and day 7, a total of 6 patients (1.2%) in the tenecteplase group and 9 (1.8%) in the placebo group died (P=0.42). Extracranial bleeding occurred in 32 patients (6.3%) in the tenecteplase group and 6 patients (1.2%) in the placebo group (P<0.001). Stroke occurred in 12 patients (2.4%) in the tenecteplase group and was hemorrhagic in 10 patients; 1 patient (0.2%) in the placebo group had a stroke, which was hemorrhagic (P=0.003). By day 30, a total of 12 patients (2.4%) in the tenecteplase group and 16 patients (3.2%) in the placebo group had died (P=0.42). CONCLUSIONS In patients with intermediate-risk pulmonary embolism, fibrinolytic therapy prevented hemodynamic decompensation but increased the risk of major hemorrhage and stroke. (Funded by the Programme Hospitalier de Recherche Clinique in France and others; PEITHO EudraCT number, 2006-005328-18; ClinicalTrials.gov number, NCT00639743.).

Pulmonary Arterial Hypertension in Patients Treated by Dasatinib

Background— The French pulmonary hypertension (PH) registry allows the survey of epidemiological trends. Isolated cases of precapillary PH have been reported in patients who have chronic myelogenous leukemia treated with the tyrosine kinase inhibitor dasatinib. Methods and Results— This study was designed to describe incident cases of dasatinib-associated PH reported in the French PH registry. From the approval of dasatinib (November 2006) to September 30, 2010, 9 incident cases treated by dasatinib at the time of PH diagnosis were identified. At diagnosis, patients had moderate to severe precapillary PH with functional and hemodynamic impairment. No other incident PH cases were exposed to other tyrosine kinase inhibitors at the time of PH diagnosis. Clinical, functional, or hemodynamic improvements were observed within 4 months of dasatinib discontinuation in all but 1 patient. Three patients required PH treatment with endothelin receptor antagonist (n=2) or calcium channel blocker (n=1). After a median follow-up of 9 months (min-max 3–36), the majority of patients did not demonstrate complete clinical and hemodynamic recovery, and no patients reached a normal value of mean pulmonary artery pressure (⩽20 mm Hg). Two patients (22%) died at follow-up (1 of unexplained sudden death and 1 of cardiac failure in the context of septicemia, respectively, 8 and 12 months after dasatinib withdrawal). The lowest estimate of incident PH occurring in patients exposed to dasatinib in France was 0.45%. Conclusions— Dasatinib may induce severe precapillary PH fulfilling the criteria of pulmonary arterial hypertension, thus suggesting a direct and specific effect of dasatinib on pulmonary vessels. Improvement is usually observed after withdrawal of dasatinib.

Prevalence, therapeutic management and medium-term prognosis of spontaneous coronary artery dissection : results from a database of 11,605 patients

OBJECTIVE To assess the prevalence, clinical presentation, therapeutic management and medium-term prognosis of spontaneous coronary artery dissection (SCAD). METHODS Over a 5-year period, and out of a cath-lab database of 11,605 files, 23 cases of SCAD were confirmed by re-analysis of angiograms. Therapeutic management and in-hospital outcome were obtained from medical files and prospective follow-up was performed. RESULTS The population consisted of 17 women and 6 men (mean age 45 years). A total of 83% of men had >/=2 cardiovascular risk factors versus only 35% of women (p=0.07). Acute coronary syndrome (ACS) was the clinical presentation in 21 cases (ST+ 61%). The prevalence of SCAD was: 0.2% in the whole population (men: 0.07%, women: 0.6%, p<0.001), and 8.7% and 10.8% in women <50 years with ACS and ST+ ACS, respectively. Left and right coronary arteries were involved in 20 (87%) and 3 (13%) cases, respectively. Coronary stenting alone was performed in 8 (35%), bypass surgery alone in 2 (9%), and both in 3 (13%) cases. Ten patients (44%) were medically managed. One patient died during hospitalization. At 1-year follow-up (100%), 77% of discharged patients were event-free. One patient died, four experienced heart failure, and none had angina or new ACS. CONCLUSION SCAD is observed in as much as 1 out 10 women <50 years presenting with ACS. After immediate coronary angiography, medical therapy is the chosen strategy in half of cases. Most patients who survive the acute phase are free from coronary events at 1 year.

Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study

Patients with severe pulmonary arterial hypertension (PAH) in New York Heart Association (NYHA) functional class (FC) III/IV have a poor prognosis, despite survival benefits being demonstrated with intravenous epoprostenol. In this pilot study, the efficacy and safety of a triple combination therapy regimen in patients with severe PAH was investigated. Data from newly diagnosed NYHA FC III/IV PAH patients (n=19) initiated on upfront triple combination therapy (intravenous epoprostenol, bosentan and sildenafil) were collected retrospectively from a prospective registry. Significant improvements in 6-min walk distance and haemodynamics were observed after 4 months’ triple combination therapy in 18 patients (p<0.01); 17 patients had improved to NYHA FC I or II. One patient was not included in the month 4 assessment (due to an emergency lung transplant in month 3). At the final evaluation (mean±sd 32±19 months), all 18 patients had sustained clinical and haemodynamic improvement. Overall survival estimates for the triple combination cohort were 100% at 1, 2 and 3 years. Expected survival calculated from the French equation was 75% (95% CI 68–82%), 60% (95% CI 50–70%) and 49% (95% CI 38–60%) at 1, 2 and 3 years, respectively. This pilot study provides preliminary evidence of the long-term benefits of upfront triple combination therapy in patients with severe PAH. Upfront triple combination therapy shows promising long-term efficacy in severe pulmonary arterial hypertension http://ow.ly/tKgHX

Diagnostic accuracy of combined cardiac troponin and copeptin assessment for early rule-out of myocardial infarction: : a systematic review and meta-analysis

Aims: This systematic review aimed to investigate the diagnostic accuracy of combined cardiac troponin (cTn) and copeptin assessment in comparison to cTn alone for early rule-out of acute myocardial infarction (AMI). Methods: Primary studies were eligible if they evaluated diagnostic accuracy for cTn with and without copeptin in patients with symptoms suggestive of AMI. AMI was defined according to the universal definition, using detection of cTn as a marker for myocardial necrosis. Eligible studies were identified by searching electronic databases (Medline, EMBASE, Science Citation Index Expanded, CINAHL, Pascal, and Cochrane) from inception to March 2013, reviewing conference proceedings and contacting field experts and the copeptin manufacturer. Results: In 15 studies totalling 8740 patients (prevalence of AMI 16%), adding copeptin improved the sensitivity of cTn assays (from 0.87 to 0.96, p=0.003) at the expense of lower specificity (from 0.84 to 0.56, p<0.001). In 12 studies providing data for 6988 patients without ST-segment elevation, the summary sensitivity and specificity estimates were 0.95 (95% CI 0.89 to 0.98) and 0.57 (95% CI 0.49 to 0.65) for the combined assessment of cTn and copeptin. When a high-sensitivity cTnT assay was used in combination with copeptin, the summary sensitivity and specificity estimates were 0.98 (95% CI 0.96 to 1.00) and 0.50 (95% CI 0.42 to 0.58). Conclusion: Despite substantial between-study heterogeneity, this meta-analysis demonstrates that copeptin significantly improves baseline cTn sensitivity. Management studies are needed to establish the effectiveness and safety of measuring copeptin in combination with high-sensitivity cTnT for early rule-out of AMI without serial testing.

Initial dual oral combination therapy in pulmonary arterial hypertension

Treatment for pulmonary arterial hypertension (PAH) has been underpinned by single-agent therapy to which concomitant drugs are added sequentially when pre-defined treatment goals are not met. This retrospective analysis of real-world clinical data in 97 patients with newly diagnosed PAH (86% in New York Heart Association functional class III−IV) explored initial dual oral combination treatment with bosentan plus sildenafil (n=61), bosentan plus tadalafil (n=17), ambrisentan plus tadalafil (n=11) or ambrisentan plus sildenafil (n=8). All regimens were associated with significant improvements in functional class, exercise capacity, dyspnoea and haemodynamic indices after 4 months of therapy. Over a median follow-up period of 30 months, 75 (82%) patients were still alive, 53 (71%) of whom received only dual oral combination therapy. Overall survival rates were 97%, 94% and 83% at 1, 2 and 3 years, respectively, and 96%, 94% and 84%, respectively, for the patients with idiopathic PAH, heritable PAH and anorexigen-induced PAH. Expected survival rates calculated from the French equation for the latter were 86%, 75% and 66% at 1, 2 and 3 years, respectively. Initial combination of oral PAH-targeted medications may offer clinical benefits, especially in PAH patients with severe haemodynamic impairment. Initial dual combination therapy may offer potential benefits in PAH patients with severe haemodynamic impairment http://ow.ly/YNxgk

Prognostic factors for extracorporeal cardiopulmonary resuscitation recipients following out-of-hospital refractory cardiac arrest. A systematic review and meta-analysis

PURPOSE Association estimates between baseline characteristics and outcomes are imprecise and inconsistent among extracorporeal cardiopulmonary resuscitation (ECPR) recipients following refractory out-of-hospital cardiac arrest (OHCA). This systematic review and meta-analysis aimed to investigate the prognostic significance of pre-specified characteristics for OHCA treated with ECPR. METHODS The Medline electronic database was searched via PubMed for articles published from January 2000 to September 2016. The electronic search was supplemented by scanning the reference lists of retrieved articles and contacting field experts. Eligible studies were historical and prospective cohort studies of adult patients undergoing ECPR following OHCA. RESULTS Fifteen primary studies were included, totaling 841 participants. The median prevalence of the primary outcome (i.e., short- or long-term survival for five studies and cerebral performance for ten studies) was 15% (range, 0-50%). The primary outcome was associated with an increased odds ratio of initial shockable cardiac rhythm (2.20; 95% confidence interval [CI], 1.30-3.72; P=0.003), shorter low-flow duration (geometric mean ratio, 0.90; 95% CI, 0.81-0.99; P=0.04), higher arterial pH value (difference, 0.12; 95% CI, 0.03-0.22; P=0.01) and lower serum lactate concentration (difference, -3.52mmol/L; 95% CI, -5.05 to -1.99; P<0.001). No significant association was found between the primary outcome and patient age (the odds of female gender and bystander CPR attempt. CONCLUSION Observational evidence from published primary studies indicates that shorter low-flow duration, shockable cardiac rhythm, higher arterial pH value and lower serum lactate concentration on hospital admission are associated with better outcomes for ECPR recipients after OHCA.

Coronary artery bypass grafting with left internal mammary artery and right gastroepiploic artery, with and without bypass

BACKGROUND Total arterial and off-pump revascularization are increasingly used in coronary artery bypass grafting. This study describes our experience with the exclusive use of both left internal thoracic artery and gastroepiploic artery by means of a median sternotomy, with and without cardiopulmonary bypass, in a subgroup of patients with two-vessel disease. METHODS From January 1995 to July 2000, 171 consecutive patients were reviewed in a prospective database. Ninety-one patients underwent coronary artery bypass grafting without cardiopulmonary bypass (group A), and 80 patients were operated on under cardiopulmonary bypass with aortic cross-clamp and cardioplegia (group B). RESULTS Patient data were similar in both groups except for the Euroscore (mean; 3.4+/-6.1, group A versus 2.5+/-4.5, group B; Euroscore > 6: 26.4%, group A versus 10%, group B; p < 0.05) and ejection fraction (mean, 54.6%+/-15.8%, group A versus 63.1%+/-12.7%, group B; p < 0.001). Severe aortic calcification was present in 6 group A patients, versus no patient in group B. Operative time was shorter in group A (185 versus 213 minutes, p < 0.0001), with less distal anastomoses (2.26 versus 2.5, p < 0.05). Conversion to cardiopulmonary bypass occurred in 1 patient, who was excluded from the study. Bleeding was higher in group A (852.6+/-288 mL versus 712.4+/-274 mL, p < 0.05), but transfusion was similar in both groups. Atrial fibrillation, postoperative inotropic support, and hospital stay were similar in both groups. Myocardial infarction was less frequent in group A (1 versus 4). Postoperative intraaortic balloon pump was used in 2 patients (group B). One patient died (group A) and 1 had an embolic stroke (group B). After discharge, 2 more patients died (group A, day 91; group B day 141), and 1 patient suffered an embolic stroke (group B). One patient in each group presented with dysfunction of the gastroepiploic artery graft requiring successful percutaneous transluminal angioplasty on the right posterolateral artery. CONCLUSIONS These results suggest that off-pump coronary artery bypass grafting using the left internal thoracic artery and gastroepiploic artery is safe even in high-risk patients. This approach allows an absolute no-touch technique of the aorta.

Inappropriate dispatcher decision for emergency medical service users with acute myocardial infarction.

OBJECTIVES Current guidelines recommend utilization of prehospital emergency medical services (EMSs) by patients with ST-elevation myocardial infarction (STEMI). The aims of this study were to estimate the percentage of inappropriate initial dispatcher decisions and determine their impact on delays in reperfusion therapy for EMS users with STEMI. METHODS As part of a prospective regional registry of patients with STEMI, we analyzed the original data for 245 patients who called a university hospital-affiliated EMS call center in France. The primary study outcome was time to reperfusion therapy calculated from the documented date and time of the first patient call. RESULTS The initial EMS dispatchers decision was appropriate (ie, dispatching a mobile intensive care unit staffed by an emergency or critical care physician) for 171 (70%) patients and inappropriate for 74 (30%) patients. Inappropriate decisions included referring the patient to a family physician (n = 59), providing medical advice (n = 9), and dispatching an ambulance (n = 6). Inappropriate initial decisions resulted in increased median time to reperfusion for 140 patients receiving fibrinolysis (95 vs 53 minutes; P < .001) and 91 patients undergoing primary percutaneous coronary intervention (170 vs 107 minutes; P < .001). In-hospital mortality was not different between the 2 study groups (6.8% vs 9.9%; P = .42). CONCLUSION The initial dispatchers decision is inappropriate for 30% of EMS users with STEMI and results in substantial delays in time to reperfusion therapy. Accuracy of telephone triage should be improved for patients who activate EMSs in response to symptoms suggestive of acute coronary syndrome.

Pulmonary artery and right ventricle assessment in pulmonary hypertension: correlation between functional parameters of ECG-gated CT and right-side heart catheterization.

Background Right ventricular function predicts outcome in patients with pulmonary hypertension (PH). Therefore accurate assessment of right ventricular function is essential to graduate severity, assess follow-up, and response to therapy. Purpose To evaluate whether PH severity could be assessed using electrocardiography-gated CT (ECG-gated CT) functional parameters. A further objective was to evaluate cardiac output (CO) using two ECG-gated CT methods: the reference Simpson technique and the fully automatic technique generated by commercially available cardiac software. Material and Methods Our institutional review board approved this study; patient consent was not required. Twenty-seven patients who had undergone ECG-gated CT and right heart catheterization (RHC) were included. Two independent observers measured pulmonary artery (PA) diameter, PA distensibility, aorta diameter, right ventricular cardiac output (CT-RVCO) and right ventricular ejection fraction (CT-RVEF) with automatic and Simpson techniques on ECG-gated CT. RHC-CO and mean pulmonary arterial pressure (mPAP) were measured on RHC. Relationship between ECG-gated CT and RHC measurements was tested with linear regression analysis. Results Inter-observer agreement was good for all measurements (r > 0.7) except for CT-RVCO calculated with Simpsons technique (r = 0.63). Pulmonary artery (PA) distensibility was significantly correlated to mPAP (r = −0.426, P = 0.027). CT-RVEF was correlated with mPAP only when issued from Simpson technique (r = −0.417, P = 0.034). CT-RVEF was not significantly correlated to RHC-CO (P > 0.2). CT-RVCO measured with Simpson technique (r = 0.487, P = 0.010) and automatic segmentation (r = 0.549, P = 0.005) correlated equally with RHC-CO. Conclusion CT-RVEF and CT-RVCO measured on ECG-gated CT are significantly correlated, respectively, to mPAP and RHC-CO in this population with severe reduction of the right ventricular ejection fraction and could be useful for evaluating and following patients with PH.