Thierry Mesana

Mechanical Circulatory Support for Advanced Heart Failure

Background—Use of wearable left ventricular assist systems (LVAS) in the treatment of advanced heart failure has steadily increased since 1993, when these devices became generally available in Europe. The aim of this study was to identify in an unselected cohort of LVAS recipients those aspects of patient selection that have an impact on postimplant survival. Methods and Results—Data were obtained from the Novacor European Registry. Between 1993 and 1999, 464 patients were implanted with the Novacor LVAS. The majority had idiopathic (60%) or ischemic (27%) cardiomyopathy; the median age at implant was 49 (16 to 75) years. The median support time was 100 days (4.1 years maximum). Forty-nine percent of the recipients were discharged from the hospital on LVAS; they spent 75% of their time out of the hospital. For a subset of 366 recipients, for whom a complete set of data was available, multivariate analysis revealed that the following preimplant conditions were independent risk factors for survival after LV...

Very Long-Term Survival Implications of Heart Valve Replacement With Tissue Versus Mechanical Prostheses in Adults <60 Years of Age

Background— Several centers favor replacing a diseased native heart valve with a tissue rather than a mechanical prosthesis, even in younger adult patients. However, long-term data supporting this approach are lacking. We examined the survival implications of selecting a tissue versus a mechanical prosthesis at initial left-heart valve replacement in a cohort of adults <60 years of age who were followed for over 20 years. Methods and Results— Comorbid and procedural data were available from 6554 patients who underwent valve replacement at our institution over the last 35 years. Of these, 1512 patients contributed follow-up data beyond 20 years, of whom 567 were adults <60 years of age at first left-heart valve operation (mean survivor follow-up, 24.0±3.1 years). Late outcomes were examined with Cox regression. Valve reoperation, often for prostheses that are no longer commercially available, occurred in 89% and 84% of patients by 20 years after tissue aortic and mitral valve replacement, respectively, and was associated with a mortality of 4.3%. There was no survival difference between patients implanted with a tissue versus a mechanical prosthesis at initial aortic valve replacement (hazard ratio 0.95; 95% CI: 0.7, 1.3; P=0.7). For mitral valve replacement patients, long-term survival was poorer than after aortic valve replacement (hazard ratio 1.4; 95% CI: 1.1, 1.8; P=0.003), but again no detrimental effect was associated with use of a tissue versus a mechanical prosthesis (hazard ratio 0.9; 95% CI 0.5, 1.4; P=0.5). Conclusions— In our experience, selecting a tissue prosthesis at initial operation in younger adults does not negatively impact survival into the third decade of follow-up, despite the risk of reoperation.

Tissue-Engineered Injectable Collagen-Based Matrices for Improved Cell Delivery and Vascularization of Ischemic Tissue Using CD133+ Progenitors Expanded From the Peripheral Blood

Background— The use of stem and/or progenitor cells to achieve potent vasculogenesis in humans has been hindered by low cell numbers, implant capacity, and survival. This study investigated the expansion of CD133+ cells and the use of an injectable collagen-based tissue engineered matrix to support cell delivery and implantation within target ischemic tissue. Methods and Results— Adult human CD133+ progenitor cells from the peripheral blood were generated and expanded by successive removal and culture of CD133− cell fractions, and delivered within an injectable collagen-based matrix into the ischemic hindlimb of athymic rats. Controls received injections of phosphate-buffered saline, matrix, or CD133+ cells alone. Immunohistochemistry of hindlimb muscle 2 weeks after treatment revealed that the number of CD133+ cells retained within the target site was >2-fold greater when delivered by matrix than when delivered alone (P<0.01). The transplanted CD133+ cells incorporated into vascular structures, and the matrix itself also was vascularized. Rats that received matrix and CD133+ cells demonstrated greater intramuscular arteriole and capillary density than other treatment groups (P<0.05 and P<0.01, respectively). Conclusions— Compared with other experimental approaches, treatment of ischemic muscle tissue with generated CD133+ progenitor cells delivered in an injectable collagen-based matrix significantly improved the restoration of a vascular network. This work demonstrates a novel approach for the expansion and delivery of blood CD133+ cells with resultant improvement of their implantation and vasculogenic capacity.

Aspirin Plus Clopidogrel Versus Aspirin Alone After Coronary Artery Bypass Grafting The Clopidogrel After Surgery for Coronary Artery Disease (CASCADE) Trial

Background— Clopidogrel inhibits intimal hyperplasia in animal studies and therefore may reduce saphenous vein graft (SVG) intimal hyperplasia after coronary artery bypass grafting. The Clopidogrel After Surgery for Coronary Artery DiseasE (CASCADE) study was undertaken to evaluate whether the addition of clopidogrel to aspirin inhibits SVG disease after coronary artery bypass grafting, as assessed at 1 year by intravascular ultrasound. Methods and Results— In this double-blind phase II trial, 113 patients undergoing coronary artery bypass grafting with SVGs were randomized to receive aspirin 162 mg plus clopidogrel 75 mg daily or aspirin 162 mg plus placebo daily for 1 year. The primary outcome was SVG intimal hyperplasia (mean intimal area) as determined by intravascular ultrasound at 1 year. Secondary outcomes were graft patency, major adverse cardiovascular events, and major bleeding. One-year intravascular ultrasound and coronary angiography were performed in 92 patients (81.4%). At 1 year, SVG intimal area did not differ significantly between the 2 groups (4.1±2.0 versus 4.5±2.1 mm2, aspirin-clopidogrel versus aspirin-placebo, P=0.44). Overall 1-year graft patency was 95.2% in the aspirin-clopidogrel group compared with 95.5% in the aspirin-placebo group (P=0.90), and SVG patency was 94.3% in the aspirin-clopidogrel group versus 93.2% in the aspirin-placebo group (P=0.69). Freedom from major adverse cardiovascular events at 1 year was 92.9±3.4% in the aspirin-clopidogrel group and 91.1±3.8% in the aspirin-placebo group (P=0.76). The incidence of major bleeding at 1 year was similar for the 2 groups (1.8% versus 0%, aspirin-clopidogrel versus aspirin-placebo, P=0.50). Conclusions— Compared with aspirin monotherapy, the combination of aspirin plus clopidogrel did not significantly reduce the process of SVG intimal hyperplasia 1 year after coronary artery bypass grafting. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00228423.Background— Clopidogrel inhibits intimal hyperplasia in animal studies and therefore may reduce saphenous vein graft (SVG) intimal hyperplasia after coronary artery bypass grafting. The Clopidogrel After Surgery for Coronary Artery DiseasE (CASCADE) study was undertaken to evaluate whether the addition of clopidogrel to aspirin inhibits SVG disease after coronary artery bypass grafting, as assessed at 1 year by intravascular ultrasound. Methods and Results— In this double-blind phase II trial, 113 patients undergoing coronary artery bypass grafting with SVGs were randomized to receive aspirin 162 mg plus clopidogrel 75 mg daily or aspirin 162 mg plus placebo daily for 1 year. The primary outcome was SVG intimal hyperplasia (mean intimal area) as determined by intravascular ultrasound at 1 year. Secondary outcomes were graft patency, major adverse cardiovascular events, and major bleeding. One-year intravascular ultrasound and coronary angiography were performed in 92 patients (81.4%). At 1 year, SVG intimal area did not differ significantly between the 2 groups (4.1±2.0 versus 4.5±2.1 mm2, aspirin-clopidogrel versus aspirin-placebo, P =0.44). Overall 1-year graft patency was 95.2% in the aspirin-clopidogrel group compared with 95.5% in the aspirin-placebo group ( P =0.90), and SVG patency was 94.3% in the aspirin-clopidogrel group versus 93.2% in the aspirin-placebo group ( P =0.69). Freedom from major adverse cardiovascular events at 1 year was 92.9±3.4% in the aspirin-clopidogrel group and 91.1±3.8% in the aspirin-placebo group ( P =0.76). The incidence of major bleeding at 1 year was similar for the 2 groups (1.8% versus 0%, aspirin-clopidogrel versus aspirin-placebo, P =0.50). Conclusions— Compared with aspirin monotherapy, the combination of aspirin plus clopidogrel did not significantly reduce the process of SVG intimal hyperplasia 1 year after coronary artery bypass grafting. Clinical Trial Registration— URL: . Unique identifier: [NCT00228423][1]. # Clinical Perspective {#article-title-35} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00228423&atom=%2Fcirculationaha%2F122%2F25%2F2680.atom

The Cardiotomy Trial: A Randomized, Double-Blind Study to Assess the Effect of Processing of Shed Blood During Cardiopulmonary Bypass on Transfusion and Neurocognitive Function

Background— Reinfusion of unprocessed cardiotomy blood during cardiac surgery can introduce particulate material into the cardiopulmonary bypass circuit, which may contribute to postoperative cognitive dysfunction. On the other hand, processing of this blood by centrifugation and filtration removes coagulation factors and may potentially contribute to coagulopathy. We sought to evaluate the effects of cardiotomy blood processing on blood product use and neurocognitive functioning after cardiac surgery. Methods and Results— Patients undergoing coronary and/or aortic valve surgery using cardiopulmonary bypass were randomized to receive unprocessed blood (control, n=134) or cardiotomy blood that had been processed by centrifugal washing and lipid filtration (treatment, n=132). Patients and treating physicians were blinded to treatment assignment. A strict transfusion protocol was followed. Blood transfusion data were analyzed using Poisson regression models. The treatment group received more intraoperative red blood cell transfusions (0.23±0.69 U versus 0.08±0.34 U, P=0.004). Both red blood cell and nonred blood cell blood product use was greater in the treatment group and postoperative bleeding was greater in the treatment group. Patients were monitored intraoperatively by transcranial Doppler and they underwent neuropsychometric testing before surgery and at 5 days and 3 months after surgery. There was no difference in the incidence of postoperative cognitive dysfunction in the 2 groups (relative risk: 1.16, 95% CI: 0.86 to 1.57 at 5 days postoperatively; relative risk: 1.05, 95% CI: 0.58 to 1.90 at 3 months). There was no difference in the quality of life nor was there a difference in the number of emboli detected in the 2 groups. Conclusions— Contrary to expectations, processing of cardiotomy blood before reinfusion results in greater blood product use with greater postoperative bleeding in patients undergoing cardiac surgery. There is no clinical evidence of any neurologic benefit with this approach in terms of postoperative cognitive function.

Long-term outcomes after valve replacement for low-gradient aortic stenosis: impact of prosthesis-patient mismatch.

Background— The long-term outcomes of patients with low-gradient aortic stenosis (LGAS) after aortic valve replacement (AVR) are poorly defined. The purpose of this study was to define the long-term outcomes of LGAS patients after AVR and to evaluate the potential impact of prosthesis–patient mismatch (PPM) in these patients. Methods and Results— A cohort of 664 patients undergoing AVR for aortic stenosis after 1990 were followed-up prospectively with annual clinical assessment and echocardiography (total follow-up 3447 patient-years; mean follow-up 5.2±3.3 years). LGAS was defined as an aortic valve area <1.2 cm2, a mean transvalvular pressure gradient <40 mm Hg, and a left ventricular (LV) ejection fraction <50%, and was present in 79 patients. Rates and correlates of survival, freedom from congestive heart failure (CHF), and LV mass regression after AVR were determined using multivariate regression methods. Ten-year survival and freedom from CHF after AVR were 72.7±7.5% and 68.2±9.5%, respectively, for patients with LGAS, compared with 89.6±1.8% and 84.1±4.2% for patients without LGAS (hazard ratio [HR] for death and postoperative CHF, 3.1±1.1 and 2.7±0.9, respectively; P<0.01). In LGAS patients, PPM, defined as an indexed effective orifice area ≤0.85 cm2/m2, was independently associated with increased rates of CHF (HR, 3.6±2.2; P=0.039), impaired LV mass regression (P=0.037), and a trend toward increased late mortality (HR, 3.0±1.9; P=0.084). Conclusions— Patients with LGAS have worse long-term outcomes after AVR compared with patients without LGAS. PPM adversely affects the long-term outcomes of LGAS patients and should be avoided in this population.

Natural History and Predictors of Outcome in Patients With Concomitant Functional Mitral Regurgitation at the Time of Aortic Valve Replacement

Background— Concomitant functional mitral regurgitation (FMR) in patients undergoing aortic valve replacement (AVR) is frequently not corrected because it may improve after AVR; however, data supporting this assumption are sparse. We ascertained the impact of clinical and echocardiographic parameters on the outcome of patients with or without concomitant FMR at the time of AVR. Methods and Results— Clinical and echocardiographic follow-up was performed on 848 patients who underwent AVR after 1990. Risk factors for mortality and a composite outcome of heart failure (CHF) symptoms, CHF death, or subsequent mitral repair or replacement, were examined with bootstrapped Cox proportional hazard models. Follow-up was 4591 patient-years (mean 5.4±3.4 years; maximum 14.2 years). FMR ≥2+ had no independent adverse effect on survival in patients with aortic stenosis (AS) or insufficiency (AI). However, AS patients with FMR ≥2+ and 1 additional risk factor (left atrial diameter >5 cm, preoperative peak aortic valve gradient <60 mm Hg, or atrial fibrillation) were at increased risk for the composite outcome (hazard ratio [HR]: 2.7; P=0.004). AI patients with FMR ≥2+ and a left ventricular end-systolic diameter <45 mm were also at risk (HR: 4.0; P=0.02). Clinical risk factors in the AS and AI subgroups were associated with an increased likelihood of mitral regurgitation ≥2+ at 18 months postoperatively. Conclusions— AS patients with FMR ≥2+ and a left atrial diameter >5 cm, preoperative peak aortic valve gradient <60 mm Hg, or atrial fibrillation have a significantly higher risk of CHF and persistent mitral regurgitation after AVR than other AS patients. AI patients with FMR ≥2+ and a left ventricular end-systolic diameter <45 mm preoperatively are also at increased risk. Others fare well after AVR.

Clinical and Echocardiographic Impact of Functional Tricuspid Regurgitation Repair at the Time of Mitral Valve Replacement

BACKGROUND The indications for tricuspid valve repair in the setting of mitral valve disease and concomitant tricuspid regurgitation (TR) remain unclear. We examined patients undergoing mitral valve replacement (MVR) to determine the effect of TR and tricuspid valve repair on survival, functional status, and postoperative TR. METHODS Between 1990 and 2005, 624 patients underwent MVR. Data included detailed serial echocardiographic tricuspid valve measurements, functional status, and survival data. Preoperative TR exceeded 2+ in 231: 125 received tricuspid repair and MVR, whereas 106 received MVR alone. Clinical and echocardiographic follow-up were complete (average, 6.8 +/- 4.8 years). Parametric and semi-parametric tests were used to analyze outcomes. RESULTS TR exceeding 2+ at operation was associated with a 53% increase in late death (p = 0.003). Tricuspid repair prevented echocardiographic progression of TR and improved congestive heart failure symptoms (both p < 0.01). Overall survival did not improve (p = 0.3). A trend to worsening TR in patients was noted with a larger tricuspid annulus diameter and without significant (<or= 1+) TR preoperatively (odds ratio, 1.4 per cm increase in annulus diameter; p = 0.5), but this was not associated with worse functional or vital outcomes. CONCLUSIONS In patients undergoing MVR, tricuspid repair is indicated when TR exceeds 2+ to alleviate heart failure symptoms, but without significantly improving survival in this population. TR of 2+ or less may not require repair. Echocardiographic tricuspid annular dimensions alone, in the absence of significant (<or= 1+) TR preoperatively, should not dictate the performance of tricuspid repair.

Comparison of clinical and echocardiographic characteristics of Streptococcus bovis endocarditis with that caused by other pathogens

The aim of our study was to compare the clinical, echographic, and prognostic features of Streptococcus bovis (S. bovis) endocarditis with those caused by other streptococci and pathogens in a large sample of patients with definite endocarditis by Duke criteria, using transesophageal echocardiography. Two hundred six patients (149 men, mean age 57 +/- 15 years) with a diagnosis of infective endocarditis formed the study population. All patients underwent multiplane transesophageal echocardiography and blood cultures. Cerebral, thoracoabdominal computed tomographic scan was performed in almost all patients (95%). All patients with S. bovis endocarditis underwent colonoscopy. Incidence of S. bovis endocarditis in our sample was 19%. Patients with S. bovis endocarditis were older than other groups. Multiple valve involvement, native valves, and large vegetations (>10 mm) were more frequent in patients with S. bovis. There was a significantly higher occurrence of embolism in the S. bovis group. Splenic embolism and multiple embolisms were significantly more frequent in patients with S. bovis. Gastrointestinal lesions, anemia, and spondylitis were observed more frequently with S. bovis endocarditis. In addition to the requirement for gastrointestinal examination for S. bovis endocarditis, our study underlines the need for systematic screening for vertebral and splenic localizations, and suggests the use of early surgery to prevent the high risk of embolism in these patients.

Minimally Invasive Coronary Artery Bypass Grafting Dual-Center Experience in 450 Consecutive Patients

Background— Minimally invasive coronary artery bypass grafting (MICS CABG) is a novel coronary operation that does not require infrastructure and is potentially available to all cardiac surgeons. It aims at decreasing the invasiveness of conventional CABG while preserving the applicability and durability of surgical revascularization. We examined the feasibility and safety of MICS CABG in the first large series of this operation to date. Methods and Results— All myocardial territories are accessed via a 4- to 6-cm left fifth intercostal thoracotomy. An apical positioner and epicardial stabilizer are introduced into the chest through the subxyphoid and left seventh intercostal spaces, respectively. The left internal thoracic artery is used to graft the left anterior descending artery, and radial artery or saphenous vein segments are used to graft the lateral and inferior myocardial territories. Proximal anastomoses are performed directly onto the aorta or from the left internal thoracic artery as a T-graft. In the first 450 consecutive MICS CABG procedures at our 2 centers, mean±SD age was 62.3±10.7 years and 123 patients were female (27%). The average number of grafts was 2.1±0.7, with complete revascularization in 95% of patients. There were 34 patients in whom cardiopulmonary bypass was used (7.6%), 17 conversions to sternotomy (3.8%), and 10 reinterventions for bleeding (2.2%). Perioperative mortality occurred in 6 patients (1.3%). Conclusions— MICS CABG is feasible and has excellent procedural and short-term outcomes. This operation could potentially make multivessel minimally invasive coronary surgery safe, effective, and more widely available.