Olivier Raisky

Changing management of cardiac myxoma based on a series of 40 cases with long-term follow-up

BACKGROUND Cardiac myxoma is generally considered to be a surgical emergency. However, as a result of progress in echocardiography and the increasing age of the patients presenting with this disease, the clinical presentation has changed and the management of cardiac myxoma now needs to be reviewed. METHODS Between 1978 and 2001, 40 patients (16 men and 24 women) between the ages of 6 months and 82 years (mean age, 55.6 years) were operated on for cardiac myxoma. Signs of heart failure with pulmonary congestion (22%) or pulmonary embolism (20%) indicated a high-risk emergency situation in some cases, whereas, in other cases (58%), the patients condition was stable and the clinical presentation was less worrying. However, the tumor was always removed within 24 hours of admission. Most cases of cardiac myxoma observed over the last decade correspond to stable forms, as echocardiography has revealed smaller tumors in generally elderly patients. RESULTS The postoperative mortality was 7.5% (3 patients). No patients were lost to follow-up, and the mean follow-up was 13.6 years. One patient was reoperated for recurrence 3 years postoperatively. Five patients required further cardiac surgery: three mitral valve replacements, one coronary artery bypass graft, and one angioplasty. The 15-year survival rate was 69%. CONCLUSIONS Myxoma tends to be observed in a more elderly and higher risk population, often at an early stage. The classic approach of emergency surgery is not always appropriate in these stable forms, allowing more thorough preoperative assessment of these patients.

CD8+ T cells induce graft vascular occlusion in a CD40 knockout donor/recipient combination

BACKGROUND It has recently been shown that treatment of animals with antibodies to CD154 (CD40L), allows for prolongation of cardiac allograft survival, but does not inhibit development of graft vasculopathy. CD8(+) T cells have been implicated in this effect. In this study we assess the role of CD40-CD154 interactions and CD40-independent CD8(+) T cells in the permanent and complete absence of CD40 by using donors and recipients genetically deficient in CD40. METHODS Hearts from BALB/c CD40(-/-) donors were transplanted into C57BL/6 CD40(-/-) recipients in the presence or absence of CD8(+) T-cell depletion. At Day 60, hearts were examined for vasculopathy using quantitative morphometry and numbers of infiltrating T cells were counted. The intragraft expression of interferon-gamma (IFN-gamma), transforming growth factor-beta1 (TGF-beta1), interleukin-4 (IL-4), eotaxin and CCR3 was assessed using competitive reverse transcription-polymerase chain reaction (RT-PCR). RESULTS In the absence of CD8(+) T-cell depletion, the mean percent intimal occlusion was 28% (with 50% of vessels showing no intimal occlusion). This figure was reduced significantly to 12% and 80% of vessels showing no intimal occlusion in mice receiving anti-CD8 antibody. Depletion of CD8(+) T cells was associated with significantly reduced intragraft IFN-gamma, TGF-beta1 and CCR3 expression, whereas mRNA production of IL-4 and eotaxin was increased. CONCLUSION Vascular intimal occlusion progresses in the complete absence of CD40-CD154 interactions, albeit to quite a small degree. The residual disease is significantly reduced by anti CD8(+) T-cell treatment, confirming the importance of CD40-CD154-independent CD8(+) T cells in the genesis of this disease.

Acute rejection and cardiac graft vasculopathy in the absence of donor-derived ICAM-1 or P-selectin

BACKGROUND ICAM-1 and P-selectin are molecules that facilitate adhesion of circulating leukocytes to vessel walls. We have investigated the role of donor-derived ICAM-1 and P-selectin in acute and chronic cardiac allograft rejection. METHODS C57BL/6J (H-2(b)) mice were used as donors for heterotopic heart transplantation into CBA/Ca (H-2(k)) recipients. The donors were wild-type or homozygous for gene mutations of ICAM-1 or P-selectin. We measured acute rejection in non-immunosuppressed recipients by daily palpation and sacrificed mice at Days 2, 4, and 6 for immunohistochemical analysis. For chronic rejection, recipients received monoclonal antibody against CD4+ T cells. We removed hearts at Days 60 to 62 for histologic assessment of vasculopathy using quantitative morphometry to measure intimal thickening. RESULTS Time (days) to rejection was 7.1 +/- 0.57 for wild-type (n = 10), 7.0 +/- 0.71 for ICAM-1 -/- (not significantly different, n = 7) and 6.1 +/- 0.33 (p = 0.001) for P-selectin -/- donors. ICAM-1 deficiency was associated with delayed infiltrate at Day 4 compared with wild-type. In the model of chronic rejection, elastin-positive vessels showed a mean occlusion of 34% +/- 3% in transplanted wild-type hearts; vessels were divided into those showing 0% to 20%, 20% to 50%, and 50% to 100% occlusion. We observed no difference in the number of affected vessels or the amount of vascular thickening in donors lacking ICAM-1 or P-selectin compared with wild-type controls. CONCLUSIONS The absence of ICAM-1 or P-selectin in donor tissues neither lengthens the time of allograft survival nor inhibits the vascular lesions associated with chronic rejection. Indeed, the absence of P-selectin may exacerbate alloimmune injury.

Identification and Characterization of Two Genes (MIP-1β, VE-CADHERIN) Implicated in Acute Rejection in Human Heart Transplantation Use of Murine Models in Tandem With cDNA Arrays

Background—Genes and mechanisms of action involved in human acute rejection after allogeneic heart transplantation remain to be elucidated. The use of a murine allograft model in tandem with cDNA arrays and quantitative real-time polymerase chain reaction (Q-PCR) can greatly help in identifying key genes implicated in human heart acute rejection. Methods and Results—Hearts from Balb/c mice were either not transplanted or transplanted heterotopically in the abdomen of Balb/c (isografts) and C57BL/6 (allografts) mice. Histological analysis showed acute rejection only in allografts. Total RNA was extracted from isografts (n=3), allografts (n=4), and not transplanted hearts (n=4); reverse transcribed; and labeled with P32. Each probe was hybridized to cDNA macroarrays. Eight genes were overexpressed and 7 genes were underexpressed in allografts compared with isografts. Macrophage inflammatory protein-1β (MIP-1β), an overexpressed gene, and VE-cadherin, an underexpressed gene, were validated by immunohistochemistry and Q-PCR in the murine models. Genes of interest, validated in the 3 murine groups, were then investigated in human heart tissues. Immunohistochemistry and Q-PCR performed on endomyocardial biopsies after heart transplantation showing no rejection (n=10) or grade IB (n=10) or IIIA (n=10) rejection, according to International Society of Heart and Lung Transplantation criteria, confirmed the results obtained from the murine model. Conclusions—We have demonstrated that the upregulation of MIP-1β and downregulation of VE-cadherin may strongly participate in human acute heart rejection.

Anesthesia management in a child with PHACE syndrome and agenesis of bilateral internal carotid arteries

This is the first case report of successful anesthesia management in a high‐risk neurological procedure in a patient with PHACE syndrome. PHACE syndrome is rare but an important clinical entity. Anesthesiologists should be aware of the neurological, otolaryngogical, and vascular risk associated with this syndrome.

Anomalous origin of the left coronary artery from the pulmonary artery: surgical treatment

Anomalous origin of the left coronary artery from the pulmonary artery is a rare malformation in which the left coronary artery originates from the pulmonary artery. The consequences are variable although, in most cases, this anomaly leads to severe coronary hypoperfusion and left ventricular dysfunction when pulmonary vascular resistances fall in the postnatal period. Surgical correction is indicated as soon as the diagnosis is established. In nearly all cases, the anomalous artery can be excised from its pulmonary origin, mobilized and reimplanted directly into the ascending aorta. In rare circumstances, technical modifications must be used to restore a normal dual coronary perfusion. The operative risk is related mainly to the severity of preoperative left ventricular dysfunction. The current mortality rate is low, but postoperative left ventricular assist device implantation may be necessary in the most severe cases. After successful revascularization, the late results are satisfactory; left ventricular function always recovers; mitral regurgitation, if present, decreases, although reoperation may be necessary for residual ischemic mitral insufficiency.

Single coronary artery and neonatal arterial switch operation: early and long-term outcomes†

OBJECTIVES The presence of single coronary artery (CA) in the arterial switch operation (ASO) for neonatal treatment with transposition of the great arteries (TGA) has been reported to be an independent risk factor for early death after surgical repair and late reintervention. The study objective was to evaluate the mortality and the CA stenosis risk at early and long term in neonatal ASO for TGA and single CA. METHODS Between January 1987 and January 2010, 979 neonates underwent an ASO, of which 73 had a single CA (7.5% of all cohort): right ostium with posterior left CA loop was the most frequent pattern (63%), followed by left ostium with an anterior right CA loop (26%). Mean age at operation was 9.3 ± 5.7 days. Mean follow-up was 9.8 years (range: 1-20 years). RESULTS Eight patients (11%) died, 6 of coronary-related death. Overall, survival was 90.1 ± 1.9% at 1 year and 88.6% ± 3.8% at 2, 5, 10 and 15 years, respectively. Independent risk factor for mortality was associated surgery before 2001. Freedom from coronary events was 91.6 ± 3.3% at 1 year and 88.7 ± 3.8% at 5, 10 and 15 years respectively. No patients required late reintervention for CA surgery or angioplasty. CONCLUSIONS All coronary-related death occurred within the first 6 months after ASO, and all patients but 1 were operated before 2001. In our experience, it appears that a single CA is not any more a risk factor for early and late mortality after ASO for TGA. Mortality has drastically reduced since 2001 and is now close to that found in TGA with standard coronary patterns. The acquired experience shared between the surgeons and the institution offsets the undeniable surgical difficulty.

Modified Konno operation for diffuse subaortic stenosis

The modified Konno operation is designed to provide relief of diffuse subaortic stenosis, while preserving the native aortic valve. The aorta and the right ventricular infundibulum are opened. The upper part of the subaortic stenosis is incised through the aortic orifice. The conal septum is incised and the septotomy is extended across the stenotic area. The obstructive tissue is removed (mainly from the left-handed rim of the septotomy) and the conal septum is enlarged with a prosthetic patch. The aorta is closed and the right ventricular infundibulum is enlarged. Early and late mortality rates are low. Potential morbidity (complete heart block, residual ventricular septal defect, iatrogenic aortic insufficiency, right ventricular outflow tract obstruction) should be minimized by a careful surgical technique. The modified Konno operation is indicated in patients with diffuse subaortic stenosis and a normal aortic orifice; this includes patients with severe forms of hypertrophic obstructive cardiomyopathy and children with tunnel subaortic stenosis and a normal aortic orifice; the modified Konno procedure provides long-lasting relief of the obstruction. In patients with tunnel stenosis and a borderline-sized aortic annulus, residual obstruction may develop at the valvar level and need reoperation; the modified Konno operation can, however, delay aortic valve replacement.

Enhanced Endogenous Adenosine Production and Protection of the Heart after Transplantation

Inhibition of adenosine metabolism and supply of nucleotide precursors resulted in marked improvement in cardiac function and increase in cardiac ATP concentration following cardioplegic arrest and hypothermic ischemia. Stimulation of endogenous adenosine production could be thus an effective treatment following cardiac transplantation.

Orthotopic heart transplantation for congenital heart defects: situs inversus.

Although rare, visceroatrial situs inversus is not exceptional in patients with complex congenital heart defects. Achieving orthotopic heart transplantation using a graft harvested in a donor with situs solitus is surgically demanding. Technical problems can, however, be overcome by adequate harvesting of donor heart and by the use of innovative reimplantation techniques. These include: separate right and left pulmonary venous anastomoses, creation of an atrio-pericardial tunnel for reimplantation of the inferior vena cava, extracardiac reconstruction of the superior vena cava pathway using the donor innominate vein, direct aortic and pulmonary arterial reconstruction after adequate mobilization. There is evidence that the early risk of heart transplantation is not increased by the presence of recipient situs inversus.