Geneviève Derumeaux

Percutaneous Transcatheter Implantation of an Aortic Valve Prosthesis for Calcific Aortic Stenosis First Human Case Description

Background— The design of a percutaneous implantable prosthetic heart valve has become an important area for investigation. A percutaneously implanted heart valve (PHV) composed of 3 bovine pericardial leaflets mounted within a balloon-expandable stent was developed. After ex vivo testing and animal implantation studies, the first human implantation was performed in a 57-year-old man with calcific aortic stenosis, cardiogenic shock, subacute leg ischemia, and other associated noncardiac diseases. Valve replacement had been declined for this patient, and balloon valvuloplasty had been performed with nonsustained results. Methods and Results— With the use of an antegrade transseptal approach, the PHV was successfully implanted within the diseased native aortic valve, with accurate and stable PHV positioning, no impairment of the coronary artery blood flow or of the mitral valve function, and a mild paravalvular aortic regurgitation. Immediately and at 48 hours after implantation, valve function was excellent, resulting in marked hemodynamic improvement. Over a follow-up period of 4 months, the valvular function remained satisfactory as assessed by sequential transesophageal echocardiography, and there was no recurrence of heart failure. However, severe noncardiac complications occurred, including a progressive worsening of the leg ischemia, leading to leg amputation with lack of healing, infection, and death 17 weeks after PHV implantation. Conclusions— Nonsurgical implantation of a prosthetic heart valve can be successfully achieved with immediate and midterm hemodynamic and clinical improvement. After further device modifications, additional durability tests, and confirmatory clinical implantations, PHV might become an important therapeutic alternative for the treatment of selected patients with nonsurgical aortic stenosis.

Effect of Cyclosporine on Reperfusion Injury in Acute Myocardial Infarction

BACKGROUND Experimental evidence suggests that cyclosporine, which inhibits the opening of mitochondrial permeability-transition pores, attenuates lethal myocardial injury that occurs at the time of reperfusion. In this pilot trial, we sought to determine whether the administration of cyclosporine at the time of percutaneous coronary intervention (PCI) would limit the size of the infarct during acute myocardial infarction. METHODS We randomly assigned 58 patients who presented with acute ST-elevation myocardial infarction to receive either an intravenous bolus of 2.5 mg of cyclosporine per kilogram of body weight (cyclosporine group) or normal saline (control group) immediately before undergoing PCI. Infarct size was assessed in all patients by measuring the release of creatine kinase and troponin I and in a subgroup of 27 patients by performing magnetic resonance imaging (MRI) on day 5 after infarction. RESULTS The cyclosporine and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before PCI. The release of creatine kinase was significantly reduced in the cyclosporine group as compared with the control group (P=0.04). The release of troponin I was not significantly reduced (P=0.15). On day 5, the absolute mass of the area of hyperenhancement (i.e., infarcted tissue) on MRI was significantly reduced in the cyclosporine group as compared with the control group, with a median of 37 g (interquartile range, 21 to 51) versus 46 g (interquartile range, 20 to 65; P=0.04). No adverse effects of cyclosporine administration were detected. CONCLUSIONS In our small, pilot trial, administration of cyclosporine at the time of reperfusion was associated with a smaller infarct by some measures than that seen with placebo. These data are preliminary and require confirmation in a larger clinical trial.

Long-Term Benefit of Postconditioning

Background— We previously demonstrated that ischemic postconditioning decreases creatine kinase release, a surrogate marker for infarct size, in patients with acute myocardial infarction. Our objective was to determine whether ischemic postconditioning could afford (1) a persistent infarct size limitation and (2) an improved recovery of myocardial contractile function several months after infarction. Methods and Results— Patients presenting within 6 hours of the onset of chest pain, with suspicion for a first ST-segment–elevation myocardial infarction, and for whom the clinical decision was made to treat with percutaneous coronary intervention, were eligible for enrollment. After reperfusion by direct stenting, 38 patients were randomly assigned to a control (no intervention; n=21) or postconditioned group (repeated inflation and deflation of the angioplasty balloon; n=17). Infarct size was assessed both by cardiac enzyme release during early reperfusion and by 201thallium single photon emission computed tomography at 6 months after acute myocardial infarction. At 1 year, global and regional contractile function was evaluated by echocardiography. At 6 months after acute myocardial infarction, single photon emission computed tomography rest-redistribution index (a surrogate for infarct size) averaged 11.8±10.3% versus 19.5±13.3% in the postconditioned versus control group (P=0.04), in agreement with the significant reduction in creatine kinase and troponin I release observed in the postconditioned versus control group (−40% and −47%, respectively). At 1 year, the postconditioned group exhibited a 7% increase in left ventricular ejection fraction compared with control (P=0.04). Conclusions— Postconditioning affords persistent infarct size reduction and improves long-term functional recovery in patients with acute myocardial infarction.

Echocardiography predicts embolic events in infective endocarditis

OBJECTIVES The aim of our study was to assess the value of transesophageal echocardiography (TEE) in predicting embolic events (EEs) in a large group of patients with definite endocarditis according to the Duke criteria, including silent embolism. BACKGROUND The value of echocardiography in predicting embolism in patients with endocarditis remains controversial. Some studies reported an increased risk of embolism in patients with large and mobile vegetations, whereas other studies failed to demonstrate such a relationship. METHODS Multiplane transesophageal echocardiograms of 178 consecutive patients with definite infective endocarditis (IE) were analyzed. The incidence of embolism was compared with the echocardiographic characteristics (localization, size and mobility) of the vegetations. To detect silent embolism, cerebral and thoraco-abdominal scans were performed in 95% of patients. RESULTS Among 178 patients, 66 (37%) had one or more EEs. There was no difference between patients with and without embolism in terms of age, gender and left valve involved. On univariate analysis, Staphylococcus infection, right-side valve endocarditis and vegetation length and mobility were significantly related to EEs. A significant higher incidence of embolism was present in patients with vegetation length >10 mm (60%, p < 0.001) and in patients with mobile vegetations (62%, p < 0.001). Embolism was particularly frequent among 30 patients with both severely mobile and large vegetations (> 15 mm) (83%, p < 0.001). On multivariate analysis, the only predictors of embolism were vegetation length (p = 0.03) and mobility (p = 0.01). CONCLUSIONS Our study shows that the presence of vegetations on TEE is predictive of embolism and that the morphologic characteristics of vegetations are helpful in predicting EEs in both mitral and aortic valve IE. It also suggests that early operation may be recommended in patients with vegetations > 15 mm and high mobility, irrespective of the degree of valve destruction, heart failure and response to antibiotic therapy.

Cyclosporine before PCI in Patients with Acute Myocardial Infarction

BACKGROUND Experimental and clinical evidence suggests that cyclosporine may attenuate reperfusion injury and reduce myocardial infarct size. We aimed to test whether cyclosporine would improve clinical outcomes and prevent adverse left ventricular remodeling. METHODS In a multicenter, double-blind, randomized trial, we assigned 970 patients with an acute anterior ST-segment elevation myocardial infarction (STEMI) who were undergoing percutaneous coronary intervention (PCI) within 12 hours after symptom onset and who had complete occlusion of the culprit coronary artery to receive a bolus injection of cyclosporine (administered intravenously at a dose of 2.5 mg per kilogram of body weight) or matching placebo before coronary recanalization. The primary outcome was a composite of death from any cause, worsening of heart failure during the initial hospitalization, rehospitalization for heart failure, or adverse left ventricular remodeling at 1 year. Adverse left ventricular remodeling was defined as an increase of 15% or more in the left ventricular end-diastolic volume. RESULTS A total of 395 patients in the cyclosporine group and 396 in the placebo group received the assigned study drug and had data that could be evaluated for the primary outcome at 1 year. The rate of the primary outcome was 59.0% in the cyclosporine group and 58.1% in the control group (odds ratio, 1.04; 95% confidence interval [CI], 0.78 to 1.39; P=0.77). Cyclosporine did not reduce the incidence of the separate clinical components of the primary outcome or other events, including recurrent infarction, unstable angina, and stroke. No significant difference in the safety profile was observed between the two treatment groups. CONCLUSIONS In patients with anterior STEMI who had been referred for primary PCI, intravenous cyclosporine did not result in better clinical outcomes than those with placebo and did not prevent adverse left ventricular remodeling at 1 year. (Funded by the French Ministry of Health and NeuroVive Pharmaceutical; CIRCUS ClinicalTrials.gov number, NCT01502774; EudraCT number, 2009-013713-99.).

Post-Conditioning Reduces Infarct Size and Edema in Patients With ST-Segment Elevation Myocardial Infarction

OBJECTIVES This study aimed to determine whether post-conditioning at the time of percutaneous coronary intervention could reduce reperfusion-induced myocardial edema in patients with acute ST-segment elevation myocardial infarction (STEMI). BACKGROUND Myocardial edema is a reperfusion injury with potentially severe consequences. Post-conditioning is a cardioprotective therapy that reduces infarct size after reperfusion, but no previous studies have analyzed the impact of this strategy on reperfusion-induced myocardial edema in humans. METHODS Fifty patients with STEMI were randomly assigned to either a control or post-conditioned group. Cardiac magnetic resonance imaging was performed within 48 to 72 h after admission. Myocardial edema was measured by T2-weighted sequences, and infarct size was determined by late gadolinium enhancement sequences and creatine kinase release. RESULTS The post-conditioned and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before percutaneous coronary intervention. As expected, post-conditioning was associated with smaller infarct size (13 ± 7 g/m(2) vs. 21 ± 14 g/m(2); p = 0.01) and creatine kinase peak serum level (median [interquartile range]: 1,695 [1,118 to 3,692] IU/l vs. 3,505 [2,307 to 4,929] IU/l; p = 0.003). At reperfusion, the extent of myocardial edema was significantly reduced in the post-conditioned group as compared with the control group (23 ± 16 g/m(2) vs. 34 ± 18 g/m(2); p = 0.03); the relative increase in T2W signal intensity was also significantly lower (p = 0.02). This protective effect was confirmed after adjustment for the size of the area at risk. CONCLUSIONS This randomized study demonstrated that post-conditioning reduced infarct size and edema in patients with reperfused STEMI.

Toward understanding response to cardiac resynchronization therapy: left ventricular dyssynchrony is only one of multiple mechanisms

AIM To date, most published echocardiographic methods have assessed left ventricular (LV) dyssynchrony (DYS) alone as a predictor for response to cardiac resynchronization therapy (CRT). We hypothesized that the response is instead dictated by multiple correctable factors. METHODS AND RESULTS A total of 161 patients (66 +/- 10 years, EF 24 +/- 6%, QRS > 120 ms) were investigated pre- and post-CRT (median of 6 months). Reduction in NYHA Class >/=1 or LV reverse remodelling (end-systolic volume reduction >/= 10%) defined response. Four different pathological mechanisms were identified. Group1: LVDYS characterized by a pre-ejection septal flash (SF) (87 patients, 54%). Elimination of SF (77 of 87 patients) resulted in reverse remodelling in 100%. Group 2: short-AV delay (21 patients, 13%) resolution (19 of 21 patients) resulted in reverse remodelling in 16 of 19. Group 3: long-AV delay (16 patients, 10%) resolution (14 of 16 patients) resulted in NYHA Class reduction >/=1 in 11 with reverse remodelling in five patients. Group 4: exaggerated LV-RV interaction (15 patients, 9%) reduced post-CRT. All responded clinically with fall in pulmonary artery pressure (P = 0.003) but did not volume respond. Group 5: patients with none of the above correctable mechanisms (22 patients, 14%). None responded to CRT. CONCLUSION CRT response is dictated by correction of multiple independent mechanisms of which LVDYS is only one. Long-axis DYS measurements alone failed to detect 40% of responders.

Effect of Cyclosporine on Left Ventricular Remodeling After Reperfused Myocardial Infarction

OBJECTIVES This study examined the effect of a single dose of cyclosporine administered at the time of reperfusion on left ventricular (LV) remodeling and function by cardiac magnetic resonance 5 days and 6 months after myocardial infarction. BACKGROUND In a human study, administration of cyclosporine at the time of acute reperfusion was associated with a smaller infarct size. METHODS Twenty-eight patients of the original cyclosporine study had an acute (at 5 days) and a follow-up (at 6 months) cardiac magnetic resonance study to determine LV volumes, mass, ejection fraction, myocardial wall thickness in infarcted and remote noninfarcted myocardium, and infarct size. RESULTS There was a persistent reduction in infarct size at 6 months in the cyclosporine group compared with the control group of patients (29 +/- 15 g vs. 38 +/- 14 g; p = 0.04). There was a significant reduction of LV end-systolic volume (and a trend for LV end-diastolic volume; p = 0.07) in the cyclosporine group compared with the control group, both at 5 days and 6 months after infarction. There was no significant difference between the 2 groups in either global LV mass or regional wall thickness of the remote noninfarcted myocardium at 5 days or 6 months. Attenuation of LV dilation and improvement of LV ejection fraction by cyclosporine at 6 months were correlated with infarct size reduction. CONCLUSIONS Cyclosporine used at the moment of acute myocardial infarction reperfusion persistently reduces infarct size and does not have a detrimental effect on LV remodeling. These results are preliminary and must be supported by further studies. (Ciclosporin A and Acute Myocardial Infarction; NCT00403728).

Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke

BACKGROUND Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. METHODS In a multicenter, randomized, open‐label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long‐term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet‐only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. RESULTS A total of 663 patients underwent randomization and were followed for a mean (±SD) of 5.3±2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet‐only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet‐only group (4.6% vs. 0.9%, P=0.02). The number of serious adverse events did not differ significantly between the treatment groups (P=0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone. CONCLUSIONS Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation. (Funded by the French Ministry of Health; CLOSE ClinicalTrials.gov number, NCT00562289.)

Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography: optimal diagnostic models using off-line tissue Doppler in the MYDISE study

AIMS To develop optimal methods for the objective non-invasive diagnosis of coronary artery disease, using myocardial Doppler velocities during dobutamine stress echocardiography. METHODS AND RESULTS We acquired tissue Doppler digital data during dobutamine stress in 289 subjects, and measured myocardial responses by off-line analysis of 11 left ventricular segments. Diagnostic criteria developed by comparing 92 normal subjects with 48 patients with coronary disease were refined in a prospective series of 149 patients referred with chest pain. Optimal diagnostic accuracy was achieved by logistic regression models, using systolic velocities at maximal stress in 7 myocardial segments, adjusting for independent correlations directly with heart rate and inversely with age and female gender (all p<0.001). Best cut-points from receiver-operator curves diagnosed left anterior descending, circumflex and right coronary disease with sensitivities and specificities of 80% and 80%, 91% and 80%, and 93% and 82%, respectively. All models performed better than velocity cut-offs alone (p<0.001). CONCLUSION Non-invasive diagnosis of coronary artery disease by quantitative stress echocardiography is best performed using diagnostic models based on segmental velocities at peak stress and adjusting for heart rate, and gender or age.