Alain Carpentier

Revival of the radial artery for coronary artery bypass grafting

Eighteen years after its first introduction for coronary artery revascularization, the radial artery (RA) was reinvestigated because of unexpected good long-term results in the early series. Since July 1989, 104 patients underwent myocardial revascularization using 122 RA grafts (18 patients received two grafts). The left internal mammary artery (IMA) was concomitantly used as a pedicled graft in 100 cases and the right IMA in 19 cases; a free IMA graft was used in 29 cases and a saphenous vein graft in 24 cases. A mean of 2.8 grafts per patient were performed. Nine patients underwent associated procedures: carotid endarterectomy (3), aortic valve replacement (3), Bigelow procedure (1), and mitral valve repair (2). The target artery receiving the RA was the circumflex (n = 59), diagonal (n = 29), right coronary (n = 27), and left anterior descending (n = 7). One patient died (0.96%) and 2 had perioperative myocardial infarct. Sternal wound infection was noted in 3 cases of double IMA implantation. No ischemia of the hand was observed. All patients received diltiazem started intraoperatively and continued after discharge. In addition aspirin (100 mg/day) was given at discharge. Early angiographic controls (less than 2 weeks) were obtained in the first 50 consecutive patients and revealed 56 of 56 patent RA grafts, 48 of 48 patent left IMA grafts, 11 of 11 patent right IMA grafts, 14 of 18 patent free IMA grafts, and 8 of 9 patent vein grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Endoscopic coronary artery bypass grafting with the aid of robotic assisted instruments

OBJECTIVE The development of endoscopic coronary artery bypass grafting has been limited because of poor visualization and increased technical difficulties in carrying out operations through ports. We investigated whether the use of robotic assisted instruments could minimize these difficulties. METHODS After a period of technical development and training on cadavers (n = 8) with the Intuitive Surgical system (Intuitive Surgical, Inc, Mountain View, Calif), the first clinical application in coronary artery surgery was performed in 4 male patients (mean age 59 +/- 6 years) with the indication of grafting the left internal thoracic artery to the left anterior descending coronary artery. Robotic assisted 3-dimensional endoscopes and instruments were introduced into the left side of the chest through 3 intercostal ports. The Heartport system (Heartport, Inc, Redwood City, Calif) was used for arresting the heart during the anastomosis. RESULTS In 2 patients, the harvesting of the left internal thoracic artery was completed endoscopically with robotic assisted instruments and the anastomosis to the left anterior descending artery was performed through a minithoracotomy with conventional instruments. In 2 other patients, the entire operation was completed endoscopically with robotic assisted instruments. Early postoperative coronary angiography demonstrated the patency of the grafts in all cases. At 6-month follow-up, all patients were free of symptoms. CONCLUSIONS Robotic assisted instruments make endoscopic coronary bypass possible and open a new era in minimally invasive surgery.

The radial artery for coronary artery bypass grafting: Clinical and angiographic results at five years☆☆☆★

OBJECTIVE The aim of this study was to assess the long-term results of use of the radial artery as a conduit for coronary artery bypass grafting. METHODS After revival of the technique in 1989, the radial artery was used as a conduit in 910 patients undergoing coronary artery bypass grafting. A complete follow-up was obtained for the first 102 consecutive patients from 4 to 7 years after the operation (mean 5.27 +/- 1.30 years). Fifty-nine percent of the patients were receiving calcium-channel inhibitors. An electrocardiographic stress test was obtained for 51 patients, with no contraindications found. Routine follow-up angiography was performed in 50 cases, including those of all patients with symptoms. Thus 64 radial artery and 48 left internal thoracic artery grafts were followed up from 4 to 7 years after the operation (mean 5.6 +/- 1.40 years). RESULTS The actuarial survival was 91.6% at 5 years, and the actuarial rate of freedom from angina was 88.7% at 5 years. Four patients underwent percutaneous transluminal angioplasty during the period of follow-up, and there were no reoperations for revision of the bypass. The electrocardiographic stress test showed negative results in 73% of cases, electrocardiographic changes alone in 21%, and clinically positive results in 6%. Angiography showed that the patency rate of the radial artery grafts was 83%. The patency rate of the left internal thoracic artery grafts (n = 47) was 91%. The difference in patency could be related to the implantation sites of the grafts, mainly the circumflex artery (51%) for the radial artery grafts and almost exclusively the left anterior descending artery (94%) for the left internal thoracic artery. CONCLUSION The use of the radial artery for coronary bypass grafting provides excellent clinical and angiographic results at 5 years. Routine use of the radial artery in combination with the left internal thoracic artery can be recommended.

The “Physio-Ring”: an advanced concept in mitral valve annuloplasty

BACKGROUND A new annuloplasty ring has been developed with the aim of adding flexibility to the remodeling annuloplasty concept. Here we report its clinical use with special emphasis on segmental valve analysis and valve sizing. METHODS From October 1992 through June 1994, 137 patients aged 4 to 76 years (mean age, 49.1 years) were operated on. The main causes of mitral valve insufficiency were degenerative, 90; bacterial endocarditis, 15; and rheumatic, 13. The indication for operation was based on the severity of the mitral valve insufficiency (90 patients were in grade III or IV) rather than on functional class (60 patients were in class III or IV). At echocardiography 6 patients had normal leaflet motion (type I), 119 leaflet prolapse (type II), and 12 restricted leaflet motion (type III). Surgical repair was carried out using Carpentier techniques of valve reconstruction. In 3 patients, inadequate ring sizing was responsible for systolic anterior motion of the anterior leaflet diagnosed by intraoperative echo. The valve was replaced in 2 patients. There were three hospital deaths, no late deaths, one reoperation for recurrent mitral valve insufficiency due to chordal rupture 1 month after repair, one reoperation for atrial thrombus formation 5 months after repair, one anticoagulant-related hemorrhage, and one thromboembolic episode. RESULTS Mid-term follow-up between 6 and 18 months was available in 94 patients. Echocardiography showed trivial or no regurgitation in 93.2% of the patients and minimal regurgitation in 6.8%. The average transmitral diastolic gradient was 3.55 +/- 1.93 mm Hg. Left ventricular end-systolic diameter and volume decreased postoperatively, demonstrating an improved left ventricular function. CONCLUSIONS This preliminary experience has provided promising results and allowed us to define the indications of the Physio-Ring versus the classic ring. It has also shown that valve sizing and proper ring selection are of primary importance.

Soluble HLA-G protein secreted by allo-specific CD4+ T cells suppresses the allo-proliferative response: A CD4+ T cell regulatory mechanism

We recently reported that the nonclassical HLA class I molecule HLA-G was expressed in the endomyocardial biopsies and sera of 16% of heart transplant patients studied. The aim of the present report is to identify cells that may be responsible for HLA-G protein expression during the allogeneic reaction. Carrying out mixed lymphocyte cultures in which the responder cell population was depleted either in CD4+ or CD8+ T cells, we found that soluble HLA-G5 protein but not the membrane-bound HLA-G isoform was secreted by allo-specific CD4+ T cells from the responder population, which suppressed the allogeneic proliferative T cell response. This inhibition may be reversed by adding the anti-HLA-G 87G antibody to a mixed lymphocyte culture. That may indicate a previously uncharacterized regulatory mechanism of CD4+ T cell proliferative response.

Human Leukocyte Antigen-G Expression After Heart Transplantation Is Associated With a Reduced Incidence of Rejection

Background—Human leukocyte antigen (HLA)-G, a nonclassic major histocompatibility complex class I molecule expressed in the extravillous cytotrophoblast at the feto-maternal interface, is known to protect the fetus from maternal cellular immunity. In a preliminary study, we showed that HLA-G is expressed in the hearts of some patients after heart transplantation. Methods and Results—In the present study, a larger number of patients was investigated to confirm this finding and to look for possible correlations between HLA-G expression and the number and types of rejection. Expression of HLA-G in endomyocardial biopsy specimens was investigated by immunohistochemical analysis, and detection of the soluble HLA-G in the serum was performed by immunoprecipitation followed by Western blot analysis. HLA-G was detected in the biopsy specimens and serum of 9 of 51 patients (18%). The number of episodes of acute rejection was significantly lower in HLA-G-positive patients (1.2±1.1) as compared with HLA-G-negative patients (4.5±2.8) (P <0.001). No chronic rejection was observed in HLA-G-positive patients, whereas 15 HLA-G-negative patients had chronic rejection (P <0.032). A longitudinal study of these patients reveals that the status of HLA-G expression was maintained after 6 months both in serum and in biopsy specimens. During this period, HLA-G-positive patients did not have chronic rejection. Conclusions—There is a significant correlation between rejection and HLA-G expression in the heart after transplantation. HLA-G expression and its effect in reducing the incidence and severity of rejection seem to be stable throughout the evolution.

Implication of HLA-G molecule in heart-graft acceptance.

HLA-G found in five of 31 heart-transplant recipients was associated with a decrease of acute and chronic rejection episodes.

Valve repair in acute endocarditis

Forty patients were operated on in the early phase of active endocarditis between 1980 and 1988. Indications for operation were heart failure (30 patients), severe valvular regurgitation (4), uncontrolled sepsis (2), septic emboli (3), and other (1 patient). Time between onset of endocarditis symptoms and operation ranged from 12 to 45 days (mean, 30 days). The aortic valve was involved in 3 patients; the mitral valve, in 28; both valves, in 7; and the tricuspid valve, in 2. There was no previous underlying valve pathology in 40%. Lesions found were cusp perforation (17 patients), annular abscess (4), vegetation (13), and chordal rupture (22). Positive blood cultures were found in 30 patients (75%). Bacterial findings were Streptococcus in 12 patients (30%), Staphylococcus in 15 (37.5%), gram-negative in 3 (7.5%), and unknown in 10 (25%). Criteria to perform valve repair were adequate antibiotic therapy for at least 1 week and large excision of all macroscopically involved tissues. In all cases, Carpentiers reconstructive techniques were used. Perioperative mortality was 2.5% (1 patient). Reoperation was necessary in 1 patient. Late mortality was 2.5% (1 patient). Repair was assessed either by angiography or by Doppler echocardiography before hospital discharge: 32 patients showed no regurgitation, whereas 7 had mild regurgitation (3 aortic, 4 mitral). Mean follow-up of 30 months was achieved in all survivors. There was no recurrence of endocarditis and no reoperation for valvular insufficiency. We conclude that valve repair in acute endocarditis is possible and effective in most instances.

Active Adaptation of the Tethered Mitral Valve Insights Into a Compensatory Mechanism for Functional Mitral Regurgitation

Background— In patients with left ventricular infarction or dilatation, leaflet tethering by displaced papillary muscles frequently induces mitral regurgitation, which doubles mortality. Little is known about the biological potential of the mitral valve (MV) to compensate for ventricular remodeling. We tested the hypothesis that MV leaflet surface area increases over time with mechanical stretch created by papillary muscle displacement through cell activation, not passive stretching. Methods and Results— Under cardiopulmonary bypass, the papillary muscle tips in 6 adult sheep were retracted apically short of producing mitral regurgitation to replicate tethering without confounding myocardial infarction or turbulence. Diastolic leaflet area was quantified by 3-dimensional echocardiography over 61±6 days compared with 6 unstretched sheep MVs. Total diastolic leaflet area increased by 2.4±1.3 cm2 (17±10%) from 14.3±1.9 to 16.7±1.9 cm2 (P=0.006) with stretch with no change in the unstretched valves despite sham open heart surgery. Stretched MVs were 2.8 times thicker than normal (1.18±0.14 versus 0.42±0.14 mm; P<0.0001) at 60 days with an increased spongiosa layer. Endothelial cells (CD31+) coexpressing &agr;-smooth muscle actin were significantly more common by fluorescent cell sorting in tethered versus normal leaflets (41±19% versus 9±5%; P=0.02), indicating endothelial-mesenchymal transdifferentiation. &agr;-Smooth muscle actin-positive cells appeared in the atrial endothelium, penetrating into the interstitium, with increased collagen deposition. Thickened chordae showed endothelial and subendothelial &agr;-smooth muscle actin. Endothelial-mesenchymal transdifferentiation capacity also was demonstrated in cultured MV endothelial cells. Conclusions— Mechanical stresses imposed by papillary muscle tethering increase MV leaflet area and thickness, with cellular changes suggesting reactivated embryonic developmental pathways. Understanding such actively adaptive mechanisms can potentially provide therapeutic opportunities to augment MV area and reduce ischemic mitral regurgitation.

Myocardial Assistance by Grafting a New Bioartificial Upgraded Myocardium (MAGNUM trial): clinical feasibility study.

BACKGROUND Cell transplantation for the regeneration of ischemic myocardium is limited by poor graft viability and low cell retention. In ischemic cardiomyopathy, the extracellular matrix is deeply altered; therefore, it could be important to associate a procedure aiming at regenerating myocardial cells and restoring the extracellular matrix function. We evaluated the feasibility and safety of intrainfarct cell therapy associated with a cell-seeded collagen scaffold grafted onto infarcted ventricles. METHODS In 20 consecutive patients presenting with left ventricular postischemic myocardial scars and indication for coronary artery bypass graft surgery, bone marrow cells were implanted during surgery. In the last 10 patients, we added a collagen matrix seeded with bone marrow cells, placed onto the scar. RESULTS There was no mortality and any related adverse events (follow-up 10 +/- 3.5 months). New York Heart Association functional class improved in both groups from 2.3 +/- 0.5 to 1.3 +/- 0.5 (matrix, p = 0.0002) versus 2.4 +/- 0.5 to 1.5 +/- 0.5 (no matrix, p = 0.001). Left ventricular end-diastolic volume evolved from 142.4 +/- 24.5 mL to 112.9 +/- 27.3 mL (matrix, p = 0.02) versus 138.9 +/- 36.1 mL to 148.7 +/- 41 mL (no matrix, p = 0.57), left ventricular filling deceleration time improved significantly in the matrix group from 162 +/- 7 ms to 198 +/- 9 ms (p = 0.01) versus the no-matrix group (from 159 +/- 5 ms to 167 +/- 8 ms, p = 0.07). Scar area thickness progressed from 6 +/- 1.4 to 9 mm +/- 1.1 mm (matrix, p = 0.005) versus 5 +/- 1.5 mm to 6 +/- 0.8 mm (no matrix, p = 0.09). Ejection fraction improved in both groups, from 25.3% +/- 7.3% to 32% +/- 5.4% (matrix, p = 0.03) versus 27.2% +/- 6.9% to 34.6% +/- 7.3% (no matrix, p = 0.031). CONCLUSIONS This tissue-engineered approach is feasible and safe and appears to improve the efficiency of cellular cardiomyoplasty. The cell-seeded collagen matrix increases the thickness of the infarct scar with viable tissue and helps to normalize cardiac wall stress in injured regions, thus limiting ventricular remodeling and improving diastolic function.