Jean-Jacques Bauchart

Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement

BACKGROUND Postprocedural aortic regurgitation occurs in 10 to 20% of patients undergoing transcatheter aortic-valve replacement (TAVR) for aortic stenosis. We hypothesized that assessment of defects in high-molecular-weight (HMW) multimers of von Willebrand factor or point-of-care assessment of hemostasis could be used to monitor aortic regurgitation during TAVR. METHODS We enrolled 183 patients undergoing TAVR. Patients with aortic regurgitation after the initial implantation, as identified by means of transesophageal echocardiography, underwent additional balloon dilation to correct aortic regurgitation. HMW multimers and the closure time with adenosine diphosphate (CT-ADP), a point-of-care measure of hemostasis, were assessed at baseline and 5 minutes after each step of the procedure. Mortality was evaluated at 1 year. A second cohort (201 patients) was studied to validate the use of CT-ADP in order to identify patients with aortic regurgitation. RESULTS After the initial implantation, HMW multimers normalized in patients without aortic regurgitation (137 patients). Among the 46 patients with aortic regurgitation, normalization occurred in 20 patients in whom additional balloon dilation was successful but did not occur in the 26 patients with persistent aortic regurgitation. A similar sequence of changes was observed with CT-ADP. A CT-ADP value of more than 180 seconds had sensitivity, specificity, and negative predictive value of 92.3%, 92.4%, and 98.6%, respectively, for aortic regurgitation, with similar results in the validation cohort. Multivariable analyses showed that the values for HMW multimers and CT-ADP at the end of TAVR were each associated with mortality at 1 year. CONCLUSIONS The presence of HMW-multimer defects and a high value for a point-of-care hemostatic test, the CT-ADP, were each predictive of the presence of aortic regurgitation after TAVR and were associated with higher mortality 1 year after the procedure. (Funded by Lille 2 University and others; ClinicalTrials.gov number, NCT02628509.).

Single high-dose erythropoietin administration immediately after reperfusion in patients with ST-segment elevation myocardial infarction: results of the erythropoietin in myocardial infarction trial.

BACKGROUND Preclinical studies and pilot clinical trials have shown that high-dose erythropoietin (EPO) reduces infarct size in acute myocardial infarction. We investigated whether a single high-dose of EPO administered immediately after reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) would limit infarct size. METHODS A total of 110 patients undergoing successful primary coronary intervention for a first STEMI was randomized to receive standard care either alone (n = 57) or combined with intravenous administration of 1,000 U/kg of epoetin β immediately after reperfusion (n = 53). The primary end point was infarct size assessed by gadolinium-enhanced cardiac magnetic resonance after 3 months. Secondary end points included left ventricular (LV) volume and function at 5-day and 3-month follow-up, incidence of microvascular obstruction (MVO), and safety. RESULTS Erythropoietin significantly decreased the incidence of MVO (43.4% vs 65.3% in the control group, P = .03) and reduced LV volume, mass, and function impairment at 5-day follow-up (all P < .05). After 3 months, median infarct size (interquartile range) was 17.5 g (7.6-26.1 g) in the EPO group and 16.0 g (9.4-28.2 g) in the control group (P = .64); LV mass, volume, and function were not significantly different between the 2 groups. The same number of major adverse cardiac events occurred in both groups. CONCLUSIONS Single high-dose EPO administered immediately after successful reperfusion in patients with STEMI did not reduce infarct size at 3-month follow-up. However, this regimen decreased the incidence of MVO and was associated with transient favorable effects on LV volume and function.

Functional decline in elderly patients presenting with acute coronary syndromes: Impact on midterm outcome

BACKGROUND Elderly patients with an acute coronary syndrome (ACS) are less likely to be enrolled into randomized, controlled trials or receive guideline-recommended therapies, because of a higher burden of comorbidity, including functional decline. AIM To assess the prognostic value of functional decline in a prospective, observational cohort of elderly ACS patients. METHODS ACS patients aged > or = 70 years were enrolled. The ACS definition included ST- and non-ST-segment elevation myocardial infarction, and unstable angina pectoris. Clinical admission and laboratory data and echocardiographic variables were recorded. Functional decline was defined as needing assisted care in daily life. The study endpoint was all-cause mortality. RESULTS Overall, 151 patients were enrolled (mean age 78 + or - 5 years; 52% men). Twenty-eight (19%) patients had functional decline. No significant difference in therapeutic management was observed between patients with functional decline and those living independently. Twenty-seven (18%) patients died during follow-up (median 447 days). Functional decline correlated with poor outcome (p = 0.008; hazard ratio [HR] 2.87 [1.31-6.25]). Other prognostic markers were diabetes, Killip class > or = II, elevated E/Ea ratio, C-reactive protein, B-type natriuretic peptide, haemoglobin, glycaemia and no coronary angiography. By multivariable analysis, C-reactive protein >13 mg/L correlated with poor outcome (p = 0.007; HR 4.77 [1.52-14.96]). There was a trend towards correlation between functional decline and poor outcome (p = 0.051; HR = 2.77 [0.99-7.72]). CONCLUSION Functional decline seems to portend poor prognosis in elderly ACS patients. Larger, community-based studies are needed to confirm these findings in a multivariable model.

Addition of B-type natriuretic peptide to the GRACE score to predict outcome in acute coronary syndrome: a retrospective (development) and prospective (validation) cohort-based study

Aims The present study was designed to build and validate a composite score based on the Global Registry of Acute Coronary Events (GRACE) score and B-type natriuretic peptide (BNP) concentrations to predict outcome in patients with acute coronary syndromes (ACS). Methods The GRACE risk score and BNP concentrations were obtained in a retrospective and a prospective cohort. A composite score including the GRACE score and BNP concentrations was first developed in a retrospective cohort of 248 patients with ACS and then validated in a prospective cohort of 575 patients. The primary outcome was 6-month death or myocardial infarction. Results End points were reached in 34 patients in the retrospective cohort and in 68 patients in the prospective cohort. Both higher BNP concentration and GRACE score were independently associated with outcome in the retrospective cohort (p=0.003 and p<0.0001). The composite score could be obtained as follows: GRACE+BNP/60. The use of the composite score increased the accuracy of the GRACE score, with an increase in the C statistic from 0.810 (0.727 to 0.892) to 0.822 (0.745 to 0.902) in the retrospective cohort and from 0.724 (0.657 to 0.791) to 0.750 (0.686 to 0.813) in the prospective cohort. Finally, 7% of patients in the prospective study population were reclassified from low to high risk or from high to low risk using this composite score. Conclusions Plasma BNP levels refine the accuracy of the GRACE score. A comprehensive risk score, which includes BNP concentration and the GRACE risk score, might improve ACS risk stratification in clinical practice.