Fabrice Bauer

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.

Outcome of patients with hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation and septal myectomy surgery.

OBJECTIVES This study was conducted to evaluate follow-up results in patients with hypertrophic obstructive cardiomyopathy (HOCM) who underwent either percutaneous transluminal septal myocardial ablation (PTSMA) or septal myectomy. BACKGROUND Controversy exists with regard to these two forms of treatment for patients with HOCM. METHODS Of 51 patients with HOCM treated, 25 were treated by PTSMA and 26 patients via myectomy. Two-dimensional echocardiograms were performed before both procedures, immediately afterwards and at a three-month follow-up. The New York Heart Association (NYHA) functional class was obtained before the procedures and at follow-up. RESULTS Interventricular septal thickness was significantly reduced at follow-up in both groups (2.3 +/- 0.4 cm vs. 1.9 +/- 0.4 cm for septal ablation and 2.4 +/- 0.6 cm vs. 1.7 +/- 0.2 cm for myectomy, both p < 0.001). Estimated by continuous-wave Doppler, the resting pressure gradient (PG) across the left ventricular outflow tract (LVOT) significantly decreased immediately after the procedures in both groups (64 +/- 39 mm Hg vs. 28 +/- 29 mm Hg for PTSMA, 62 +/- 43 mm Hg vs. 7 +/- 7 mm Hg for myectomy, both p < 0.0001). At three-month follow-up, the resting PG remained lower in the PTSMA and myectomy groups (24 +/- 19 mm Hg and 11 +/- 6 mm Hg, respectively, vs. those before procedures, both p < 0.0001). The NYHA functional class was also significantly improved in both groups (3.5 +/- 0.5 vs. 1.9 +/- 0.7 for PTSMA, 3.3 +/- 0.5 vs. 1.5 +/- 0.7 for myectomy, both p < 0.0001). CONCLUSIONS Both myectomy and PTSMA reduce LVOT obstruction and significantly improve NYHA functional class in patients with HOCM. However, there are benefits and drawbacks for each therapeutic method that must be counterbalanced when deciding on treatment for LVOT obstruction.

Aortic valve replacement for Low-Flow/Low-Gradient aortic stenosis - Operative risk stratification and long-term outcome: A European Multicenter study

OBJECTIVES We evaluated a large multicenter series of patients operated on for low-flow/low-gradient aortic stenosis (LF/LGAS) to stratify the operative risk, assess whether perioperative mortality has decreased over recent years, and analyze the post-operative outcome. BACKGROUND Although LF/LGAS is classically associated with a high operative risk, few data are available concerning the results of surgery in this setting. METHODS A total of 217 consecutive patients (168 men, 77%) with severe aortic stenosis (area <1 cm(2)), low ejection fraction (EF) (<or=35%), and low mean gradient (MG) (<or=30 mm Hg) who underwent aortic valve replacement (AVR) between 1990 and 2005 were included. RESULTS Perioperative mortality was 16% and decreased dramatically from 20% in the 1990 to 1999 period to 10% in the 2000 to 2005 period. Higher European System for Cardiac Operative Risk Evaluation score (EuroSCORE), very low MG and EF, New York Heart Association functional class III or IV, history of congestive heart failure, and multivessel coronary artery disease (MVD) were associated with perioperative mortality. On multivariate analysis, very low pre-operative MG and MVD were predictors of excess perioperative mortality. In the subgroup of patients with dobutamine stress echocardiography, the absence of contractile reserve was a strong predictor of perioperative mortality. Overall 5-year survival rate was 49 +/- 4%. Lower MG, higher EuroSCORE, prior atrial fibrillation, and MVD were identified as independent predictors of overall long-term mortality. CONCLUSIONS In view of the very poor prognosis of unoperated patients, the current operative risk, and the long-term outcome after surgery, AVR is the treatment of choice in the majority of cases of LF/LGAS.

Acute Improvement in Global and Regional Left Ventricular Systolic Function After Percutaneous Heart Valve Implantation in Patients With Symptomatic Aortic Stenosis

Background—The newly developed percutaneous heart valve (PHV) implantation technique decreases transaortic pressure gradient in patients with aortic stenosis. PHV replacement effects on left ventricular (LV) global and regional systolic function are currently unknown. Methods and Results—Eight patients with severe aortic stenosis had 2D echocardiography at baseline and 24 hours after PHV implantation to evaluate changes in LV volume and LV ejection fraction. Regional function, ie, both peak systolic anterior and posterior wall tissue velocity, as well as strain and strain rate imaging, were measured by tissue Doppler imaging from a short-axis view. At 24 hours, a significant reduction in transaortic mean pressure gradient (from 46±15 to 8±3 mm Hg; P<0.0001) was accompanied by an increase in aortic valve area (from 0.59±0.11 to 1.69±0.11 cm2; P<0.0001). LV end-diastolic volume remained unchanged (102±36 to 101±12 mL; P=NS), whereas LV ejection fraction increased (48±18% to 57±12%; P<0.01). Improvement in posterior wall displacement (posterior wall tissue velocity increased from 2.2±0.5 to 4.4±1.0 cm/s−1; P=0.0003) and deformation (strain rate imaging increased from 1.0±0.3 to 1.9±0.7 s−1, P=0.009, and strain increased from 11±5% to 17±9%; P=0.02) were observed. Conclusions—Immediately after PHV replacement, improvement of LV global and regional systolic function was evidenced by tissue Doppler imaging.

Percutaneous Transcatheter Implantation of an Aortic Valve Prosthesis for Calcific Aortic Stenosis

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.

Evaluation of Left Ventricular Diastolic Function with Cardiac MR Imaging

Assessment of left ventricular (LV) function with cardiac magnetic resonance (MR) imaging is often limited to evaluation of systolic function, including analysis of regional wall motion, measurement of mass and volume, and estimation of ejection fraction. However, diastolic dysfunction is present in various heart diseases, particularly in heart failure with preserved ejection fraction, which is increasingly prevalent and is associated with a poor prognosis. In daily practice, the assessment of diastolic function is mainly performed with transthoracic echocardiography. Evaluation of diastolic function with cardiac MR imaging is seldom performed in clinical practice. However, basic assessment of LV relaxation and stiffness abnormalities can be achieved with MR imaging by using a combination of left atrium size measurement and phase-contrast evaluation of transmitral flow. In addition, assessment of pulmonary venous flow and the LV filling curve can also be performed. Furthermore, MR imaging with late gadolinium enhancement sequences provides insight into the extent of myocardial fibrosis, which strongly influences LV stiffness. Finally, phase-contrast evaluation of tissue velocities, myocardial tagging, MR spectroscopy, and MR elastography are promising tools for a better understanding of LV diastolic function but require further evaluation.

Current aspects of the spectrum of acute heart failure syndromes in a real-life setting: the OFICA study.

To improve knowledge of epidemiological data, management, and clinical outcome of acute heart failure (AHF) in a real‐life setting in France.

Arteriogenic Therapy by Intramyocardial Sustained Delivery of a Novel Growth Factor Combination Prevents Chronic Heart Failure

Background— Therapeutic angiogenesis is a promising approach for the treatment of cardiovascular diseases, including myocardial infarction and chronic heart failure. We aimed to improve proangiogenic therapies by identifying novel arteriogenic growth factor combinations, developing injectable delivery systems for spatiotemporally controlled growth factor release, and evaluating functional consequences of targeted intramyocardial growth factor delivery in chronic heart failure. Methods and Results— First, we observed that fibroblast growth factor and hepatocyte growth factor synergistically stimulate vascular cell migration and proliferation in vitro. Using 2 in vivo angiogenesis assays (n=5 mice per group), we found that the growth factor combination results in a more potent and durable angiogenic response than either growth factor used alone. Furthermore, we determined that the molecular mechanisms involve potentiation of Akt and mitogen-activated protein kinase signal transduction pathways, as well as upregulation of angiogenic growth factor receptors. Next, we developed crosslinked albumin-alginate microcapsules that sequentially release fibroblast growth factor-2 and hepatocyte growth factor. Finally, in a rat model of chronic heart failure induced by coronary ligation (n=14 to 15 rats per group), we found that intramyocardial slow release of fibroblast growth factor-2 with hepatocyte growth factor potently stimulates angiogenesis and arteriogenesis and prevents cardiac hypertrophy and fibrosis, as determined by immunohistochemistry, leading to improved cardiac perfusion after 3 months, as shown by magnetic resonance imaging. These multiple beneficial effects resulted in reduced adverse cardiac remodeling and improved left ventricular function, as revealed by echocardiography. Conclusion— Our data showing the selective advantage of using fibroblast growth factor-2 together with hepatocyte growth factor suggest that this growth factor combination may constitute an efficient novel treatment for chronic heart failure.

Feasibility and safety of early discharge after transfemoral transcatheter aortic valve implantation with the Edwards SAPIEN-XT prosthesis.

There is currently no consensus on the duration of hospitalization required after transfemoral transcatheter aortic valve implantation (TAVI). We report the feasibility and safety of early discharge after TAVI with the Edwards SAPIEN-XT prosthesis. From 2009 to 2013, 337 patients underwent transfemoral TAVI with the Edwards SAPIEN-XT prosthesis using local anesthesia and were discharged home either early (≤3 days, Early Discharge group, n = 121) or after 3 days (Late Discharge group, n = 216). The primary end point of the study combined death and rehospitalization from discharge to 30-day follow-up. Patients in the Early Discharge group were less symptomatic (New York Heart Association class ≥III: 64.5% vs 75.5%, p = 0.01) and had less renal failure (creatinine: 102.1 ± 41.0 vs 113.3 ± 58.9 μmol/L, p = 0.04), atrial fibrillation (33.1% vs 46.3%, p = 0.02), and previous balloon aortic valvuloplasty (11.6% vs 23.1%, p = 0.01) and were more likely to have a pacemaker before TAVI (16.5% vs 8.3%, p = 0.02). Pre-existing pacemaker (p = 0.05) and the absence of acute kidney injury (p = 0.02) were independent predictors of an early discharge, whereas previous balloon aortic valvuloplasty (p = 0.03) and post-TAVI blood transfusions (p = 0.002) were independent predictors of late discharge. The primary end point occurred in 4 patients (3.3%) in the Early Discharge group and in 11 patients (5.1%) in the Late Discharge group (p = 0.58). In conclusion, the results of our study suggest that early discharge after transfemoral TAVI using the Edwards SAPIEN-XT prosthesis is feasible and safe in selected patients.

Improvement of Peripheral Endothelial Dysfunction by Protein Tyrosine Phosphatase Inhibitors in Heart Failure

Background— Chronic heart failure (CHF) induces endothelial dysfunction characterized by a decrease in nitric oxide (NO) production in response to flow (flow-mediated dilatation [FMD]). Because activation of endothelial NO synthase (eNOS) by flow requires tyrosine phosphorylation, we tested whether endothelial dysfunction could be corrected by increasing phosphotyrosine levels using protein tyrosine phosphatase (PTP) inhibitors and especially inhibitors of PTP1B. Methods and Results— CHF was induced by coronary ligation in mice, and FMD was assessed in isolated and cannulated mesenteric artery segments (2 mm in length and <300 &mgr;m in diameter). CHF almost abolished FMD but only moderately affected the response to acetylcholine. In mice with CHF, the PTP1B inhibitors AS279, AS098, and AS713 restored FMD to levels similar to those of normal mice. This restoration was reduced by inhibitors of eNOS and phosphatidylinositol-3 kinase. Polymerase chain reaction and Western blot showed that arteries express PTP1B, and this expression was not affected by CHF. Immunolocalization revealed the presence of PTP1B in the endothelium and the adventitia. Flow induced a transient eNOS phosphorylation that was absent in CHF. PTP1B inhibition stimulated early eNOS phosphorylation and increased phosphorylation of Akt. Conclusions— Our results demonstrate for the first time that PTP1B inhibitors may be potent treatments for endothelial dysfunction.