Pascal Gueret

Transcatheter aortic valve implantation: early results of the FRANCE (FRench Aortic National CoreValve and Edwards) registry

AIMS Transcatheter aortic valve implantation is a therapeutic alternative for high-surgical-risk patients with severe symptomatic aortic stenosis. Two models of prosthesis are currently commercialized in France, which can be implanted either via a transarterial or a transapical approach. The aim of the study was to evaluate in a national French registry the early safety and efficacy of transcatheter aortic valve replacement (AVR) using either the Edwards SAPIEN™ or CoreValve™ in high-surgical-risk patients with severe aortic stenosis. METHODS AND RESULTS The multicentre national registry was conducted in 16 centres between February 2009 and June 2009, under the authority of the French Societies of Cardiology and Thoracic and Cardio-Vascular Surgery. The primary endpoint was mortality at 1 month. Two hundred and forty-four high-surgical-risk patients (logistic EuroSCORE ≥20%, STS ≥10%, or contra-indication to AVR) were enrolled. Mean age was 82 ± 7 years and 43.9% were female. Edwards SAPIEN and CoreValve were implanted in 68 and 32% of patients, respectively. The approaches used were transarterial (transfemoral: 66%; subclavian: 5%) or transapical in 29%. Device success rate was 98.3% and 30-day mortality was 12.7%. Severe complications included stroke (3.6%), tamponade (2%), acute coronary occlusion (1.2%), and vascular complications (7.3%). Pacemaker was required in 11.8%. At 1 month, 88% of patients were in NYHA class II or less. CONCLUSION This prospective registry reflects the real-life experience of transcatheter aortic valve implantation in high-risk elderly patients in France. The early results are satisfactory in terms of feasibility, short-term haemodynamic and functional improvement, and safety. Longer term follow-up will be further assessed.

Low-Gradient Aortic Stenosis Operative Risk Stratification and Predictors for Long-Term Outcome: A Multicenter Study Using Dobutamine Stress Hemodynamics

Background The prognostic value of dobutamine stress hemodynamic data in the setting of low‐gradient aortic stenosis has been addressed in small, single‐center studies. Larger studies are needed to define the criteria for selecting the patients who will benefit from valve replacement. Methods and Results Six centers prospectively enrolled 136 patients with aortic stenosis (96 men; median age, 72 years [range, 65 to 77 years]; median aortic valve area, 0.7 cm2 [range, 0.6 to 0.8]; mean transaortic gradient, 29 mm Hg [range, 23 to 34 mm Hg]; cardiac index, 2.11 L min‐1 m‐2 [range, 1.75 to 2.55 L min‐1 m‐2]). Left ventricular contractile reserve on the dobutamine stress Doppler study was present in 92 patients (group I) and absent in 44 patients (group II). Operative mortality was 5% (3 of 64 patients) in group I compared with 32% (10 of 31 patients) in group II (P=0.0002). Predictors for operative mortality were the lack of contractile reserve (odds ratio, 10.9; 95% confidence interval [CI], 2.6 to 43.4; P=0.001) and a mean transaortic gradient ≤20 mm Hg (odds ratio, 4.7; 95% CI, 1.1 to 21.0; P=0.04). Predictors for long‐term survival were valve replacement (hazard ratio, 0.30; 95% CI, 0.17 to 0.53; P=0.001) and left ventricular contractile reserve (hazard ratio, 0.40; 95% CI, 0.23 to 0.69; P=0.001). Conclusions In the setting of low‐gradient aortic stenosis, surgery seems beneficial for most of the patients with left ventricular contractile reserve. In contrast, the postoperative outcome of patients without reserve is compromised by a high operative mortality. Thus, dobutamine stress Doppler hemodynamics may be factored into the risk‐benefit analysis for each patient. (Circulation. 2003;108:319‐324.)

Comparison of Thrombolysis Followed by Broad Use of Percutaneous Coronary Intervention With Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Acute Myocardial Infarction : Data From the French Registry on Acute ST-Elevation Myocardial Infarction (FAST-MI)

Background— Intravenous thrombolysis remains a widely used treatment for ST-elevation myocardial infarction; however, it carries a higher risk of reinfarction than primary PCI (PPCI). There are few data comparing PPCI with thrombolysis followed by routine angiography and PCI. The purpose of the present study was to assess contemporary outcomes in ST-elevation myocardial infarction patients, with specific emphasis on comparing a pharmacoinvasive strategy (thrombolysis followed by routine angiography) with PPCI. Methods and Results— This nationwide registry in France included 223 centers and 1714 patients over a 1-month period at the end of 2005, with 1-year follow-up. Sixty percent of the patients underwent reperfusion therapy, 33% with PPCI and 29% with intravenous thrombolysis (18% prehospital). At baseline, the Global Registry of Acute Coronary Events score was similar in thrombolysis and PPCI patients. Time to initiation of reperfusion therapy was significantly shorter in thrombolysis than in PPCI (median 130 versus 300 minutes). After thrombolysis, 96% of patients had coronary angiography, and 84% had subsequent PCI (58% within 24 hours). In-hospital mortality was 4.3% for thrombolysis and 5.0% for PPCI. In patients with thrombolysis, 30-day mortality was 9.2% when PCI was not used and 3.9% when PCI was subsequently performed (4.0% if PCI was performed in the same hospital and 3.3% if performed after transfer to another facility). One-year survival was 94% for thrombolysis and 92% for PPCI (P=0.31). After propensity score matching, 1-year survival was 94% and 93%, respectively. Conclusions— When used early after the onset of symptoms, a pharmacoinvasive strategy that combines thrombolysis with a liberal use of PCI yields early and 1-year survival rates that are comparable to those of PPCI.

Association of Changes in Clinical Characteristics and Management With Improvement in Survival Among Patients With ST-Elevation Myocardial Infarction

CONTEXT The contemporary decline in mortality reported in patients with ST-segment elevation myocardial infarction (STEMI) has been attributed mainly to improved use of reperfusion therapy. OBJECTIVE To determine potential factors-beyond reperfusion therapy-associated with improved survival in patients with STEMI over a 15-year period. DESIGN, SETTING, AND PATIENTS Four 1-month French nationwide registries, conducted 5 years apart (between 1995, 2000, 2005, 2010), including a total of 6707 STEMI patients admitted to intensive care or coronary care units. MAIN OUTCOME MEASURES Changes over time in crude 30-day mortality, and mortality standardized to the 2010 population characteristics. RESULTS Mean (SD) age decreased from 66.2 (14.0) to 63.3 (14.5) years, with a concomitant decline in history of cardiovascular events and comorbidities. The proportion of younger patients increased, particularly in women younger than 60 years (from 11.8% to 25.5%), in whom prevalence of current smoking (37.3% to 73.1%) and obesity (17.6% to 27.1%) increased. Time from symptom onset to hospital admission decreased, with a shorter time from onset to first call, and broader use of mobile intensive care units. Reperfusion therapy increased from 49.4% to 74.7%, driven by primary percutaneous coronary intervention (11.9% to 60.8%). Early use of recommended medications increased, particularly low-molecular-weight heparins and statins. Crude 30-day mortality decreased from 13.7% (95% CI, 12.0-15.4) to 4.4% (95% CI, 3.5-5.4), whereas standardized mortality decreased from 11.3% (95% CI, 9.5-13.2) to 4.4% (95% CI, 3.5-5.4). Multivariable analysis showed a consistent reduction in mortality from 1995 to 2010 after controlling for clinical characteristics in addition to the initial population risk score and use of reperfusion therapy, with odds mortality ratios of 0.39 (95%, 0.29-0.53, P <.001) in 2010 compared with 1995. CONCLUSION In France, the overall rate of cardiovascular mortality among patients with STEMI decreased from 1995 to 2010, accompanied by an increase in the proportion of women younger than 60 years with STEMI, changes in other population characteristics, and greater use of reperfusion therapy and recommended medications.

Influence of Preoperative Left Ventricular Contractile Reserve on Postoperative Ejection Fraction in Low-Gradient Aortic Stenosis

Background— Dobutamine stress hemodynamics (DSH) has the potential to stratify operative risk in low-gradient aortic stenosis (AS), but little is known about the relation between left ventricle contractile reserve and postoperative left ventricular ejection fraction (LVEF). We sought to assess the value of DSH to predict postoperative improvement in LVEF. Methods and Results— Sixty-six consecutive patients with symptomatic severe AS (aortic valve area ≤1 cm2), LVEF ≤40%, and mean pressure gradient ≤40 mm Hg prospectively enrolled in the French multicenter study on low-gradient AS and who survived to aortic valvular replacement (AVR) were included. Preoperative contractile reserve was present in 46 patients (group I; 70%) and absent in 20 patients (group II; 30%). In the overall sample, 58% of patients improved by 2 New York Heart Association (NYHA) classes after AVR. Mean LVEF improved from 29±6% to 47±11% (P<0.0001). LVEF improved by ≥10 EF units in 38 patients (83%) in group I and in 13 patients (65%) in group II. Mean LVEF improvement was similar in the 2 groups (19±10% versus 17±11%; P=0.54). On multivariable analysis, multivessel coronary artery disease (P=0.05) and baseline mean transaortic pressure gradient (P=0.01) were related to LVEF improvement, whereas contractile reserve was not. Conclusions— LVEF increases in the majority of patients with low-gradient AS who survive after AVR. Although the absence of contractile reserve on DSH is related to high operative mortality, it does not predict the absence of LVEF recovery in patients surviving to AVR. These data further support the concept that surgery should not be contraindicated on the basis of absence of contractile reserve alone.

Impact of Prehospital Thrombolysis for Acute Myocardial Infarction on 1-Year Outcome Results From the French Nationwide USIC 2000 Registry

Background—Limited data are available on the impact of prehospital thrombolysis (PHT) in the “real-world” setting. Methods and Results—Of 443 intensive care units in France, 369 (83%) prospectively collected all cases of infarction (≤48 hours of symptom onset) in November 2000; 1922 patients (median age, 67 years; 73% men) with ST-segment–elevation infarction were included, of whom 180 (9%) received intravenous thrombolysis before hospital admission (PHT). Patients with PHT were younger than those with in-hospital thrombolysis, primary percutaneous interventions, or no reperfusion therapy. Median time from symptom onset to hospital admission was 3.6 hours for PHT, 3.5 hours for in-hospital lysis, 3.2 hours for primary percutaneous interventions, and 12 hours for no reperfusion therapy. In-hospital death was 3.3% for PHT, 8.0% for in-hospital lysis, 6.7% for primary percutaneous interventions, and 12.2% for no reperfusion therapy. One-year survival was 94%, 89%, 89%, and 79%, respectively. In a multivariate analysis of predictors of 1-year survival, PHT was associated with a 0.49 relative risk of death (95% CI, 0.24 to 1.00; P=0.05). When the analysis was limited to patients receiving reperfusion therapy, the relative risk of death for PHT was 0.52 (95% CI, 0.25 to 1.08; P=0.08). In patients with PHT admitted in ≤3.5 hours, in-hospital mortality was 0% and 1-year survival was 99%. Conclusions—The 1-year outcome of patients treated with PHT compares favorably with that of patients treated with other modes of reperfusion therapy; this favorable trend persists after multivariate adjustment. Patients with PHT admitted very early have a very high 1-year survival rate.

Magnetic resonance imaging of targeted catheter-based implantation of myogenic precursor cells into infarcted left ventricular myocardium.

OBJECTIVES This study was designed to test the hypothesis that myocardial implantation of myogenic precursor cells (MPC) loaded with iron oxide can be reliably detected in vivo by cardiac magnetic resonance imaging (MRI). BACKGROUND In vivo imaging of targeted catheter-based implantation of MPC into infarcted left ventricular (LV) myocardium is unavailable. METHODS The study was conducted in seven farm pigs (four with anterior myocardial infarction), in which autologous MPC were injected through a percutaneous catheter allowing for LV electromechanical mapping and guided micro-injections into normal and infarcted myocardium. Cardiac MRI was used to detect implanted MPC previously loaded with iron oxide nanoparticles. RESULTS Magnetic resonance imaging data were compared with LV electromechanical mapping and cross-registered pathology. All 9 injections into normal and 12 injections into locally damaged myocardium were detected on T2-weighted spin echo and inversion-recovery true-fisp MRI (low signal areas) with good anatomical concordance with sites of implantation on electromechanical maps. All sites of injection were confirmed on pathology that showed in all infarct animals iron-loaded MPC at the center and periphery of the infarct as expected from MRI. CONCLUSIONS Targeted catheter-based implantation of iron-loaded MPC into locally infarcted LV myocardium is accurate and can be reliably demonstrated in vivo by cardiac MRI. The ability to identify noninvasively intramyocardial cell implantation may be determinant for future experimental studies designed to analyze subsequent effects of such therapy on detailed segmental LV function.

Major impact of admission glycaemia on 30 day and one year mortality in non-diabetic patients admitted for myocardial infarction: results from the nationwide French USIC 2000 study

Objective: To analyse the short and long term prognostic significance of admission glycaemia in a large registry of non-diabetic patients with acute myocardial infarction. Methods: Assessment of short and long term prognostic significance of admission blood glucose in a consecutive population of 1604 non-diabetic patients admitted to intensive care units in France in November 2000 for a recent (⩽ 48 hours) myocardial infarction. Results: In-hospital mortality, compared with that of patients with admission glycaemia below the median value of 6.88 mmol/l (3.7%), rose gradually with each of the three upper sextiles of glycaemia: 6.5%, 12.5% and 15.2%. Conversely, one year survival decreased from 92.5% to 88%, 83% and 75% (p < 0.001). Admission glycaemia remained an independent predictor of in-hospital and one year mortality after multivariate analyses accounting for potential confounders. Increased admission glycaemia also was a predictor of poor outcome in all clinical subsets studied: patients without heart failure on admission, younger and older patients, patients with or without reperfusion therapy, and patients with or without ST segment elevation. Conclusion: In non-diabetic patients, raised admission blood glucose is a strong and independent predictor of both in-hospital and long term mortality.

Bypassing the emergency room reduces delays and mortality in ST elevation myocardial infarction. The USIC 2000 registry

Objective: To study the impact on outcomes of direct admission versus emergency room (ER) admission in patients with ST-segment elevation myocardial infarction (STEMI) Design: Nationwide observational registry of STEMI patients Setting: 369 intensive care units in France. Interventions: Patients were categorised on the basis of the initial management pathway (direct transfer to the coronary care unit or catheterisation laboratory versus transfer via the ER). Main outcome measures: Delays between symptom onset, admission and reperfusion therapy. Mortality at five days and one year. Results: Of 1204 patients enrolled, 66.9% were admitted direct and 33.1% via the ER. Bypassing the ER was associated with more frequent use of reperfusion (61.7% v 53.1%; p  =  0.001) and shorter delays between symptom onset and admission (244 (interquartile range 158) v 292 (172) min; p < 0.001), thrombolysis (204 (150) v 258 (240) min; p < 0.01), hospital thrombolysis (228 (156) v 256 (227) min, p  =  0.22), and primary percutaneous coronary intervention (294 (246) v 402 (312) min; p < 0.005). Five day mortality rates were lower in patients who bypassed the ER (4.9% v 8.6%; p  =  0.01), regardless of the use and type of reperfusion therapy. After adjusting for the simplified Thrombolysis in Myocardial Infarction (TIMI) risk score, admission via the ER was an independent predictor of five day mortality (odds ratio 1.67, 95% confidence interval 1.01 to 2.75). Conclusions: In this observational analysis, bypassing the ER was associated with more frequent and earlier use of reperfusion therapy, and with an apparent survival benefit compared with admission via the ER.

Evaluation of carotid artery and aortic intima-media thickness measurements for exclusion of significant coronary atherosclerosis in patients scheduled for heart valve surgery

OBJECTIVES We assessed the value of carotid intima-media thickness (CIMT) and thoracic aorta intima-media thickness (AoIMT) in ruling out significant coronary artery disease (CAD) in patients scheduled for heart valve surgery. BACKGROUND Evaluation of CAD is needed in most patients undergoing heart valve surgery because of the high surgical morbidity in patients with significant CAD, raising the need for sensitive tests to exclude CAD. Coronary angiography is the reference standard, but this invasive procedure is not cost-effective, because more than two-thirds of these patients do not have significant CAD. METHODS In a pilot study, CIMT and AoIMT cutoff values separating low- from high-risk groups were determined in 96 patients by using receiver-operating characteristic curves. Then, a prospective study was conducted in 152 patients to determine the statistical power of these cutoff values used alone or in combination. In both studies, carotid artery ultrasonography and transesophageal echocardiography were performed before coronary angiography and valve surgery. RESULTS In the pilot study, CIMT < 0.55 mm and AoIMT < 3 mm were excellent predictors of the absence of CAD. In the prospective study, CIMT and AoIMT criteria were independent predictors of significant CAD in these patients, as assessed by logistic regression analysis. Carotid IMT criterion had 100% sensitivity and 100% negative predictive value. For the AoIMT criterion, sensitivity was 98%, and negative predictive value 99%. Combining the two criteria did not change sensitivity and negative predictive value but increased specificity to 78%. CONCLUSIONS Measurements of CIMT and AoIMT may be useful in selecting patients who do not require coronary angiography before heart valve surgery.