Christian Latremouille

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.

Is It Reasonable to Treat All Calcified Stenotic Aortic Valves With a Valved Stent?: Results From a Human Anatomic Study in Adults

OBJECTIVES This study was designed to study the behavior of a stent deployed inside human stenotic aortic valves. BACKGROUND Endovascular valved stent (VS) implantation is a promising new therapy for patients with severe calcific aortic stenosis (AS). The precise characteristics of stent deployment in humans have been poorly studied so far. METHODS Thirty-five patients with severe AS were included in the study. Sixteen patients (46%) had bicuspid aortic valves. A self-expandable stent specifically designed for VS implantation was deployed intraoperatively inside the aortic valve before surgical aortic valve replacement. RESULTS In tricuspid aortic valves, the shape of stent deployment was circular, triangular, or elliptic in 68%, 21%, or 11%, respectively. Noncircular stent deployment was frequent in bicuspid aortic valves (the elliptic deployment being the rule [79%]), and stent underdeployment was constant. The incidence of gaps between the stent external surface and the aortic valve did not differ between tricuspid and bicuspid valves (58% vs. 43%; p = 0.49). Sharp calcific excrescences protruding inside the stent lumen were present in 3 cases (9%). Ex vivo study of a homemade VS confirmed that the regularity of the coaptation line of the leaflets was critically dependent on the presence or the absence of stent misdeployment. CONCLUSIONS Stent misdeployment was constant in bicuspid valves and occurred in one-third of cases of tricuspid valves. Premature failure of implanted VS (secondary to valve distortion or traumatic injury to the leaflets by calcific excrescences) might be an important concern in the future.

Long-Term Results of Mitral Valve Repair in Active Endocarditis

Background—Several investigators have reported the feasibility of mitral valve repair in active endocarditis, but the long-term results are still unknown. Methods and Results—We reviewed 37 consecutive patients who underwent mitral valve repair with the Carpentier technique for active endocarditis in our center between 1989 and 1994. This repair involved prosthetic annuloplasty in 31 patients (84%), valve resection in 31 (84%), chordal shortening or transposition in 19 (51%), pericardial patch in 16 (43%), and direct suture of leaflet perforation in 4 (11%). Associated procedures were primarily aortic valve repair or replacement in 11 (30%) and tricuspid repair in 2 (6%). Early complications included 1 operative death (3%; 95% CI, 0 to 15.5) and 1 reoperation for pericardial patch dehiscence. Recurrence of endocarditis was observed in 1 patient (3%; 95% CI, 0 to 16). The 10-year survival rate and freedom from mitral valve reoperation were 80% (95% CI, 66 to 94) and 91% (95% CI, 81 to 100), respectively. At 10 years, most patients (96%) were in good functional status (NYHA class I to II) with no or trivial mitral regurgitation (92%) on echocardiography. Conclusions—Mitral valve repair using Carpentier’s techniques in patients with active endocarditis offers very good long-term results with a low rate of recurrence or reoperation.

Dynamic aortomyoplasty to assist left ventricular failure

The efficacy of skeletal muscle contractile force to augment left ventricular function has been demonstrated experimentally and clinically by the cardiomyoplasty procedure. Another approach in biomechanical cardiac assistance is the use of electrostimulated skeletal muscle in an extracardiac position. We describe an autologous counterpulsating device using the native ascending aorta as a ventricular chamber wrapped by an electrostimulated latissimus dorsi muscle flap (LDMF). This model avoids thrombotic complications observed in skeletal muscle neo-ventricles associated with prosthetic chambers. In 8 goats, a right LDMF was transferred to the thoracic cavity by removal of the second rib. In 4 goats, the diameter of the aorta was enlarged by surgical implantation (using lateral clamping) of an autologous pericardial patch. The LDMF was wrapped around the ascending aorta and electrostimulated using an external diastolic pulse generator connected to a sensing myocardial lead and to LDMF pacing electrodes. Hemodynamic studies were performed (left ventricular, aortic, and pulmonary artery pressures and rate of rise of left ventricular pressure). The LDMF diastolic counterpulsation was performed using a burst of 30 Hz, with a delay from the R wave adjusted to provide optimal diastolic augmentation. Percent increase in the subendocardial viability index was calculated during unassisted and assisted cardiac cycles (1:2) at baseline and after acute heart failure induced by the administration of high doses of propranolol hydrochloride (3 mg/kg intravenously). Diastolic aortic counterpulsation by the stimulated LDMF resulted in a significant improvement in the subendocardial viability index both at baseline and after induced cardiac failure in both groups, though the increase was greater in the group with aortic enlargement.

First clinical use of a bioprosthetic total artificial heart: report of two cases

BACKGROUND The development of artificial hearts in patients with end-stage heart disease have been confronted with the major issues of thromboembolism or haemorrhage. Since valvular bioprostheses are associated with a low incidence of these complications, we decided to use bioprosthetic materials in the construction of a novel artificial heart (C-TAH). We report here the device characteristics and its first clinical applications in two patients with end-stage dilated cardiomyopathy. The aim of the study was to evaluate safety and feasibility of the CARMAT TAH for patients at imminent risk of death from biventricular heart failure and not eligible for transplant. METHODS The C-TAH is an implantable electro-hydraulically actuated pulsatile biventricular pump. All components, batteries excepted, are embodied in a single device positioned in the pericardial sac after excision of the native ventricles. We selected patients admitted to hospital who were at imminent risk of death, having irreversible biventricular failure, and not eligible for heart transplantation, from three cardiac surgery centres in France. FINDINGS The C-TAH was implanted in two male patients. Patient 1, aged 76 years, had the C-TAH implantation on Dec 18, 2013; patient 2, aged 68 years, had the implantation on Aug 5, 2014. The cardiopulmonary bypass times for C-TAH implantation were 170 min for patient 1 and 157 min for patient 2. Both patients were extubated within the first 12 postoperative hours and had a rapid recovery of their respiratory and circulatory functions as well as a normal mental status. Patient 1 presented with a tamponade on day 23 requiring re-intervention. Postoperative bleeding disorders prompted anticoagulant discontinuation. The C-TAH functioned well with a cardiac output of 4·8-5·8 L/min. On day 74, the patient died due to a device failure. Autopsy did not detect any relevant thrombus formation within the bioprosthesis nor the different organs, despite a 50-day anticoagulant-free period. Patient 2 experienced a transient period of renal failure and a pericardial effusion requiring drainage, but otherwise uneventful postoperative course. He was discharged from the hospital on day 150 after surgery with a wearable system without technical assistance. After 4 months at home, the patient suffered low cardiac output. A change of C-TAH was attempted but the patient died of multiorgan failure. INTERPRETATION This preliminary experience could represent an important contribution to the development of total artificial hearts using bioprosthetic materials. FUNDING CARMAT SA.

Increased Radial Force Improves Stent Deployment in Tricuspid but Not in Bicuspid Stenotic Native Aortic Valves

BACKGROUND Stent deployment within stenotic native aortic valves has been shown to depend on valve anatomy (presence of bicuspid valve or not). This study investigated the influence of stent stiffness on stent expansion. METHODS The study included 88 patients with severe aortic stenosis, and 36 (41%) had bicuspid aortic valves. Two self-expandable stents with different radial force were deployed intraoperatively inside stenotic aortic valves before surgical aortic valve replacement. Patients in group B received a stent stiffer than that in group A. Effect of stent radial force on stent shape and incidence of paraprosthetic gaps was determined. RESULTS Noncircular stent deployment was more frequent in bicuspid (81%) than in tricuspid aortic valves (33%; p < 0.0001). Increasing stent radial force significantly improved stent shape in tricuspid valves (circular shape: 60% in group A vs 93% in group B; p = 0.005) but had no significant effect in bicuspid valves (12.5% in group A vs 27% in group B;p = 0.394). Likewise, incidence of paraprosthetic gaps was significantly reduced with the stiff stent in tricuspid valves (64% in group A vs 30% in group B, p = 0.025) but not in bicuspid valves (50% in group A vs 60% in group B; p= 0.722). CONCLUSIONS Increased stent radial force had a favorable effect on stent deployment in tricuspid but not in bicuspid valves. In bicuspid valves, stent maldeployment was constant. Leaflet distortion of implanted valved stent might be a concern in this setting.

Reoperation for Failure of Mitral Valve Repair in Degenerative Disease: A Single-Center Experience

BACKGROUND The purpose of this study was to report our 19-year experience in redo surgery for failure of mitral valve repair (MVRep) in degenerative disease. METHODS From 1987 to 2006, 43 consecutive patients (32 males) underwent either redo MVRep (n = 21) or redo mitral valve replacement (n = 22) for failure of MVRep. Age ranged from 10 to 78 years (median, 59 years). Forty-one patients (95%) had grade 3+ or greater mitral regurgitation, and 3 patients had chronic systolic anterior motion of the anterior leaflet of the mitral valve. Repair was mainly performed using Carpentiers techniques. RESULTS There was no perioperative death in the MVRep group and 2 deaths in the redo mitral valve replacement group. In univariate analysis, long-term survival was significantly superior in the MVRep group compared with redo mitral valve replacement (p = 0.011). There were three reoperations (14%) in the MVRep group for recurrent severe mitral regurgitation. One patient (5%) in the redo mitral valve replacement group underwent reoperation for prosthetic endocarditis. The 7-year freedom from reoperation rate was 95% (95% confidence interval, 84% to 99%) in both groups. At the latest follow-up, 16 (94%) patients in the MVRep group were in New York Heart Association I or II functional status. Fifteen (88%) had no or mild mitral regurgitation on echocardiography. Two patients (12%) presented with moderate (2+) mitral regurgitation. CONCLUSIONS In case of failure of MVRep for severe degenerative mitral valve disease, re-repair is feasible in about 50% of the patients with encouraging results at 7 years.

Accelerated arterial stiffening and gene expression profile of the aorta in patients with coronary artery disease.

Background Hypertension and chronic renal failure (CRF) are considered models of accelerated arterial stiffening. Arterial stiffness increases further when CRF is associated with hypertension. We hypothesized that, in patients with mild CRF, aortic gene expression profile would include genes involved in arterial calcifications and enlargement. Method We analysed human aorta with the ‘GeneChip Microarray’ technology, in patients with or without CRF, scheduled for a coronary artery bypass graft. Results Nine of 25 patients had high-quality RNA and were included in the study. Among the 101 transcripts differentially expressed between CRF patients and controls, 97 transcripts were overexpressed in CRF patients. Two genes had the highest overexpression in CRF patients: lumican (LUM), involved in the regulation of collagen fibrillogenesis; and ornithine decarboxylase (ODC1), involved in polyamine biosynthesis, smooth muscle cell growth and proliferation. Immunohistochemical staining revealed an increased amount of LUM and ODC1 in the vascular smooth muscle cells (VSMCs) of CRF compared to non-CRF aortic sections. Eight genes were implicated in the regulation of the cytoskeleton (including capping protein muscle Z-line 1 α and moesin) and cell migration, and five genes were implicated in extracellular matrix function and apoptosis. A trend towards an upregulation of candidate genes involved in arterial calcifications was observed in CRF patients, but did not reach statistical significance. Carotid-femoral pulse wave velocity was not correlated with gene expression level. Conclusion In conclusion, these results show that patients at an early stage of CRF have a specific gene expression profile of aortic tissue and suggest that genes implicated in collagen fibrillogenesis, and VSMCs migration and proliferation, particularly LUM and ODC1, may play a role.

Bridge to transplantation with the DeBakey VAD® axial pump: a single center report

AIMS To report our experience with a left ventricular assist device axial pump as a bridge to transplantation: the DeBakey Ventricular Assist Device (VAD). METHODS From February 1999 to February 2002, nine patients (among which eight males), with a mean age of 47 years, all in NYHA functional class IV, were proposed for a bridge to transplantation with the DeBakey VAD. Five patients had primary dilated cardiomyopathy, four had ischemic cardiomyopathy. All the patients had inotropic support prior to the intervention (dobutamine with a mean dose of 12 mcg/kg per min), six had an intra-aortic counterpulsation, four presented ventricular rhythm disorders. Interventions were performed through sternotomy alone (no need for an abdominal pocket) under extra-corporeal circulation on beating heart (except in one patient suffering from an apical thrombosis for which cardioplegic arrest was performed) as followed: implantation of the apical inflow cannula, tunneling of the percutaneous cable, implantation of the outflow graft under aortic side clamping, starting of the DeBakey VAD during CPB weaning-off. RESULTS Mean support duration was 81+/-62 days (16-224 days). Eight reoperations were required (three for bleeding or cardiac tamponade, one for haemoperitoneum, one for aortic bifurcation thrombectomy, one for right ventricular assist device implantation, two for iterative replacements of the DeBakey VAD). A significant hemolysis was observed in two patients. No device infection or dysfunction were observed. Secondary recovery of a pulsed flow was observed either clinically or by Echo-Doppler in six patients. Five patients were transplanted, four died prior to transplantation (three from multi-organ failure on post-operative day 35, 16 and 50, respectively, and the last patient was found disconnected at day 109). CONCLUSIONS The DeBakey VAD is at the origin of renewed interest for continuous flow assist devices. Still under evaluation, the advantages of miniaturization and facility of implantation of this new device seem to be promising.

Congenital mitral valve regurgitation in adult patients. A rare, often misdiagnosed but repairable, valve disease

OBJECTIVE Congenital mitral valve regurgitation (MVR) is a rare disease occurring in infancy or childhood. Although congenital MVR has been described in adults, no surgical series has been reported so far. We describe here a 6-year surgical experience of congenital MVR in adults at a single institution. METHODS We reviewed the data of 15 consecutive patients (8 men), aged more than 16 years (median: 38 years; range: 16-70 years) operated on for severe congenital MVR from June 2000 to March 2006. Congenital MVR represented 2.1% of mitral valve surgery performed in adults during the same period. Patients with atrio-ventricular septal defect or atrio-ventricular discordance were excluded. RESULTS The congenital MVR was preoperatively diagnosed in six (40%) cases. Two (13%) patients had a Williams-Beuren syndrome. The lesions consisted in annular dilation (100%), prolapsed leaflet (87%), chordal abnormalities (80%), papillary muscle abnormalities (40%) or valvular cleft (33%). Mitral valve repair was performed in all cases using Carpentiers techniques. There was no hospital death or late mortality. At last follow-up (median: 60 months; range: 6-83 months), all patients were in NYHA functional class I or II and in a sinus rhythm. On transthoracic echocardiography, 11 (73%) patients had no or trivial MVR. Mild MVR was present in four (27%) patients. No patient was reoperated and endocarditis did not occur. CONCLUSION Congenital MVR is rare in adults, often misdiagnosed and accessible to valve repair with excellent mid-term results.