Cyclosporine-related posterior reversible encephalopathy syndrome after heart transplantation: should we withdraw or reduce cyclosporine?: case reports.

Cyclosporine (CsA) related encephalopathy has not been well documented after heart transplantation. We report 2 cases of posterior reversible encephalopathy syndrome (PRES). The first case was a 68-year-old woman who underwent heart transplantation and received immunosuppression with mycophenolate mofetil, prednisone, and CsA. On day 14, she developed arterial hypertension, headache, visual disturbances, and generalized seizures. Fluid-attenuated inversion recovery magnetic resonance imaging (MRI) of the brain showed diffuse and bilateral high signals in the frontal posterior and the occipital areas. The second case was a 19-year-old man with a heart transplant receiving immunosuppression with prednisone and CsA. On day 44, he developed acute headache and generalized seizures. T2-weighted MRI of the brain showed diffuse high signals in the cerebellum, right lenticular and occipital areas. In both cases blood CsA concentration was therapeutic. Both cases recovered but in the first case neurologic findings were reversed only after CsA withdrawal.

[Enterovirus-related pericarditis and mediastinitis after heart surgery: a case report]. / Péricardite et médiastinite à entérovirus après chirurgie cardiaque: description d'un cas.

We report a case of enterovirus related pericarditis associated to mediastinitis in a hospitalised 53-year-old male after heart surgery. Mediastinitis caused by enterovirus has not previously been described.

Identification and characterization of two genes (MIP-1beta, 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-1beta (MIP-1beta), 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-1beta and downregulation of VE-cadherin may strongly participate in human acute heart rejection.

[Whipple's disease endocarditis: report of 5 cases and review of the literature]. / Endocardites de la maladie de Whipple: cinq observations et revue de la littérature.

PURPOSE: Endocarditic lesions (infectious endocarditis) associated with Whipple's disease are exceptional. We report five cases from the cardiovascular and pneumologic hospital Louis Pradel in Lyon. METHOD: We have collected all cases of Tropheryma whipplei endocarditis diagnosed between 1995 and 2004. RESULTS: Five men with a mean age of 53 years at time of diagnosis. The symptoms were essentially cardiovascular: murmur, embolism in 3 cases, and heart failure secondary to valvular insufficiency in 2 cases. The valvular involvement, double in 3 cases, was more often aortic. Vegetations were present in all patients and valvular destruction sometimes very important. A low grade fever was present in 4 cases, associated with weight loss in 2 cases. The only extra-cardiac symptoms were arthralgias or arthritis in all cases, considered in 3 patients as seronegative rheumatoid arthritis, B27+ spondylarthritis, and psoriasic arthritis. Their was no other clinical manifestations of Whipple's disease, particularly digestive, ocular, neurologic or adenopathy, and duodenal biopsies secondarily performed in 4 cases were non contributive. This differs from literature as an extra-cardiac location was identified in 11 out of 17 cases. The diagnosis was obtained by histology and PCR on the cardiac valves, as all the patients underwent surgery. The evolution was favourable with a prolonged antibiotic therapy. CONCLUSIONS: These report confirms the existence of endocarditic forms of the Whipple's disease, in which the single extra-cardiac manifestation is rheumatologic, and reminds us the usefulness of histology and PCR on the cardiac valves at the time of valvular surgery.

[Emergent transcatheter aortic valve implantation in a patient with bicuspid aortic valve stenosis in cardiogenic shock]. / Choc cardiogénique sur bicuspidie aortique sténosante traité par remplacement valvulaire aortique percutané en urgence.

Transcatheter aortic valve implantation is a therapeutic option for high-risk patients with severe aortic valve stenosis and with cardiac symptoms. This procedure requires the preliminary evaluation by a "heart team" and presents some contraindications. We report the case of a 58-year-old man with severe bicuspid aortic valve stenosis and cardiogenic shock. In spite of contraindications and because of the failure of balloon aortic valvuloplasty, transcatheter aortic valve implantation was performed in emergency.

Thiopurine S-methyltransferase gene polymorphism is predictive of azathioprine-induced myelosuppression in heart transplant recipients.

Azathioprine (AZA) is metabolized via the cytosolic enzyme thiopurine S-methyltransferase (TPMT). TPMT activity exhibits genetic polymorphism with four prevalent (75%) mutant alleles TPMT*2 (G238C) and TPMT*3 (A719G and/or G460A) and a wild-type allele TPMT*1. To test the hypothesis that presence of these mutations is associated with greater toxicity of AZA in heart transplant recipients, 30 consecutive patients treated with AZA were followed up for the first month after heart transplant. Mutation of TPMT gene (mutation-specific polymerase chain reaction-based methods) was observed in four patients (A719G: n = 2; A719G plus G460: n = 2). Agranulocytosis did not occur in patients with the wild genotype. It occurred in the two patients with mutation A719G and there was a 40% drop in neutrophils in the two other patients. Discontinuation of AZA in the four mutant patients corrected for the drop. Presence of TPMT mutations is associated with a greater likelihood of agranulocytosis. Determination of these mutations could reduce the risk for hematological side-effects.

Outcome of atrial fibrillation after mitral valve repair.

OBJECTIVE: The aim of the study was to evaluate the prognostic factors for return to sinus rhythm after mitral valve repair. METHOD: One hundred ninety-one patients underwent surgery for mitral valve repair, including 142 procedures for valve repair only (74%). The patients with preoperative atrial fibrillation (50.5%) were older, clinically more symptomatic, and had a greater degree of left atrial dilation than the patients who had sinus rhythm. RESULTS: Preoperative cardiac rhythm, the duration of preoperative atrial fibrillation, and a lesser degree of left atrial hypertrophy are significant prognostic factors independent of the maintenance of sinus rhythm. The probability of return to stable sinus rhythm was 93.7% when sinus rhythm was already present before the operation and 80% when atrial fibrillation was intermittent or of less than 1 year's duration; probability declined abruptly for durations over 1 year. No significant difference in patient survival was noted between those who had sinus rhythm (99% +/- 0.9% at 1 year and 86% +/- 6.6% at 5 years) and those who had atrial fibrillation in the preoperative period (95% +/- 3.1% at 1 year and 86% +/- 8.4% at 5 years). In contrast, the postoperative return to sinus rhythm was associated with 99% +/- 0.9% and 94% +/- 4.8% survivals at 1 and 4 years versus 97% +/- 1.5% and 77% +/- 13% in the event of postoperative atrial fibrillation. CONCLUSION: The aim of restoring postoperative sinus rhythm after mitral valve repair should lead to surgery being conducted on patients who have sinus rhythm or recent-onset atrial fibrillation. Surgery for atrial fibrillation may be of value in patients with a long history of atrial fibrillation, providing that it does not induce prohibitive excess mortality.

Design of an isolated pig heart preparation for positron emission tomography and magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Validation of new positron emission tomography (PET) tracers or magnetic (MR) imaging contrast agents is based on isolated rodent heart preparations. The use of larger animals could provide a more direct validation using the devices used for humans. METHODS: An isolated pig heart preparation has been developed and adapted to the technical constraints of whole body PET and MR imaging. This preparation could be used either in the Langendorff or working mode after selective cannulation of both coronary arteries. RESULTS: The authors showed that quantification of regional kinetics of PET tracers was possible using this preparation by measuring fluorine-18-labeled deoxyglycose (18FDG) kinetics in remote and ischemic territories. Experiments using MR imaging contrast agents, for myocardial perfusion, demonstrated the ability of this preparation to accurately validate these contrast agents over a wide range of flow rates. CONCLUSIONS: An isolated pig heart preparation could be developed to fulfill the constraints of PET and MR imaging, and proved useful for the study of the distribution of different tracers or contrast media developed for functional cardiac imaging in humans.

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.

Long conservation organs in heart transplantation: postoperative results and long-term follow-up in fourteen patients.

Between 1988 and 1995, 14 heart transplantations were performed after a long preservation period (10 to 13 hours). The transplantation procedure (Shumway) was standard, and our results were achieved through the implementation of a very strict reperfusion technique that included low pressure and low cardiopulmonary bypass output for the first 10 minutes. Three patients died during the postoperative period, and the survival rate was 75% at 1 year and 71% at 5 years. The results obtained with hearts stored for such long periods are comparable to the results obtained with hearts stored for less than 4 hours.

Long-term follow-up of small (size 20 and 21) Medtronic-Hall aortic valve prostheses.

BACKGROUND: Our goal was to study the long-term follow-up of patients having aortic valve replacement and to focus particularly on the patients receiving small prostheses. METHODS: Four hundred twenty-eight Medtronic-Hall valves were implanted (156 size 20 or 21 mm, 149 size 22 or 23 mm, and 123 size 25 or 27 mm). Group 20-21 had a higher number of female patients, more associated coronary lesions, and more patients with aortic stenosis. RESULTS: The actuarial survival rate at 8 years was 80% for group 20-21, 80% for group 22-23, and 76% for group 25-27 (p = not significant). In group 20-21, the actuarial event-free rates at 8 years were as follows: thromboembolic complications, 94%; prosthetic valve endocarditis, 99%; reoperation, 98%; and hemorrhagic complications, 78%. The only factors of prognostic value in this group were age and associated coronary lesions. CONCLUSIONS: The durable nature of the results obtained with the Medtronic-Hall 20- and 21-mm prostheses compared with large-diameter prostheses allows the use of a simple and reliable surgical technique and should mean that indications for ring enlargement become rare.

Subdiaphragmatic implantation of implantable cardioverter defibrillator generator.

Despite several improvements in the surgical technique and in the technologic design of cardioverter defibrillators made over the past years, abdominal placement of the generator device, done as Mirowski did it in his first implantation performed in 1980, remains the widely used method. Although smaller defibrillators are available, they remain bulky and are a source of local complications. To prevent such complications and to enhance patient comfort, we performed a subdiaphragmatic implantation in 31 patients.

Intracardiac air clearing in valvular surgery guided by transesophageal echocardiography.

BACKGROUND AND AIMS OF THE STUDY: Air embolism during open heart surgery seems to be a common occurrence and may be responsible for neuropsychological deficit or myocardial damage. MATERIAL AND METHODS: Forty-two consecutive patients undergoing valvular surgery were studied using the long axis view of the heart by two dimensional transesophageal echocardiography (TEE). The patients were randomized into two groups of 21 each. In group 1, the routine air evacuation method was used. In group 2, the same air evacuation method was used and controlled with a Doppler ultrasonic probe adjusted around the root of the aorta. At the end of air evacuation, intracardiac microbubbles and retained air were analyzed with TEE and when air was founded, its location was communicated to the surgeons who tried to remove it by shaking the heart and tilting the operating table for 15 minutes. The patients were assessed for detection of cardiac or neurological postoperative complications. RESULTS: The incidences of microbubbles and retained air were 57% and 43% in group 1, and 62% and 38% in group 2 respectively (ns). The mean grade of microbubbles was lower in group 2: 1.4 +/- 0.8 vs. 2.2 +/- 0.9, p < 0.05. TEE allowed to significantly decrease (p < 0.05) retained air and mean grade of microbubbles to 14% and 1.3 +/- 0.8 in group 1, and to 10% and 0.8 +/- 0.8 in group 2, without statistical difference between the two groups. Despite the help of TEE, manual attempts to eradicate retained air were unsuccessful in five patients (three in group 1, two in group 2). CONCLUSIONS: The use of aortic ultrasonic probe allowed to reduce the amount of microbubbles. TEE was a useful tool not only for the detection of retained air but also for locating it, and guiding the procedure to eliminate it.

Mechanical cardiac valve thrombosis in patients in critical hemodynamic compromise.

BACKGROUND: Valve obstruction is a life threatening complication of mechanical valve prosthesis. METHODS: From 1985 to 1993, 29 consecutive patients were hospitalized in our intensive care unit for mechanical prosthetic valve thrombosis (PVT). There were 12 men and 17 women aged 25-75 years (57 +/- 12). Prosthetic valve location was mitral in 14 patients, aortic in 6, aortic and mitral in 9. PVT occurred from 15 days to 174 months (67 +/- 52 months) after surgery. Delay from first symptoms to hospitalization ranged from 1 to 45 days (11 +/- 11). RESULTS: First clinical symptoms were progressive left heart failure in 17 patients, stroke in 6, and chest pain in 6. Furthermore, acute myocardial infarction was later documented in 3. Left heart failure NYHA III-IV was present in 26 patients (90%) on admission and 10 of those were in cardiogenic shock. Anticoagulation regimen was inadequate in 13 cases (45%). It has been recently stopped in 8 patients and incorrectly conducted in 5. Total hospital mortality was 41.3% (12). It was independent of type and position of the valve prosthesis. Diagnosis of PVT was only made at autopsy in 3 patients who died of recurrent myocardial infarction (2) or cardiogenic shock (1). Five further patients died before any surgery could be attempted (cardiac arrest: 2, cardiogenic shock: 3). Valve replacement could be done in 21 cases, 7 of whom were in cardiogenic shock and 9 had severe pulmonary edema. Four patients died after surgery, the operative mortality was 19%. CONCLUSION: PVT remains a serious complication of mechanical heart valve prostheses. Overall mortality rate is high, related to difficulty to diagnosis, delay to hospitalization and severe clinical condition at admission. In our study, operative risk remained acceptable even when the clinical presentation was severe.

Alteration of the left ventricular contractile reserve in heart transplant patients: a dobutamine stress strain rate imaging study.

BACKGROUND: Strain rate imaging (SRI), a recently developed Doppler-derived process, allows quantification of myocardial systolic function. We investigate whether SRI quantifies the contractile reserve during dobutamine stress tests in heart transplant patients (HT), when compared with normal individuals. METHODS: An incremental dobutamine test (5 to 40 microg/kg per minute) was performed in 10 HT and 15 control subjects, all of whom displayed normal coronary angiography. Gray-scale and color myocardial Doppler data were acquired in standard B-mode views at baseline, low-dose, peak, and recovery. Longitudinal SR was processed from the myocardial velocities for each segment. The changes in maximal systolic SR were used to quantify myocardial contractile reserve. RESULTS: Dobutamine infusion failed to induce clinical symptoms or electrocardiographic (ECG) changes in either group. Visually determined wall motion score was considered normal in all segments for each stage of the dobutamine stress. Heart rate was augmented similarly in both groups during dobutamine infusion. In controls, systolic SR increased gradually with incremental dobutamine dose and returned to baseline values upon recovery. Conversely, in HT patients, the increase in systolic SR was blunted at peak dobutamine, at which point it was significantly different vs controls. CONCLUSIONS: Quantitative assessment of myocardial function using SRI during dobutamine stress revealed an impaired contractile reserve in HT patients with normal coronary angiography. These subtle changes in regional myocardial function could not be identified using visual wall motion scoring. Additional studies are necessary to evaluate whether SR imaging detection of contractile reserve impairment will improve clinical efficiency or event prediction in this population.

Crystalloid versus cold blood cardioplegia in patients operated on for myocardial revascularisation.

Post-ischemic reperfusion phenomenon has been studied in two methods of myocardial protection: a crystalloid cardioplegia (St Thomas no.2) and a cold blood cardioplegia (Buckberg) during cardiopulmonary bypass for myocardial revascularisation in patients. Myocardial protection has been assessed from the evolution of hemodynamic parameters, reperfusion arrhythmias and biochemical analysis of the coronary flow after cross-clamp removal: creatinine phosphokinase (CPK_MB) and nucleotide adenine metabolites (adenosine, inosine, hypoxanthine, xanthine and uric acid). The study was performed in two groups of 14 patients. Hemodynamic conditions were similar in both groups during reperfusion in order to avoid different coronary flow. In those conditions, myocardial protection by cold blood cardioplegia reduced reperfusion arrhythmias, and resulted in a loss of CPK-MB release. Furthermore, the reduction of metabolites release, purine bases and oxypurine bases into coronary sinus after cold blood cardioplegia suggest a better protection of myocardial high energy phosphates in this group than after crystalloid cardioplegia. Our results also show that hypoxanthine is probably the final product of ATP degradation in human myocardial tissue.

Defibrillation threshold and electrode configurations: an experimental study testing three configurations in twelve pigs.

OBJECTIVE: The choice between epicardial or subcutaneous patches remains unclear and depends essentially on the team's habits. This study tested how much an additional patch can decrease defibrillation threshold (DFT), and compared a Subcutaneous Array and an epicardial patch. Today most implantable automatic defibrillators have a transvenous endocardial configuration alone but when the DFT remains high an additional patch is necessary. EXPERIMENTAL DESIGN: Three different configurations were tested with biphasic shocks in 12 pigs: Endovenous lead (Endo), Endovenous lead + subcutaneous patch (Endo + SQ) and Endovenous lead + epicardial patch (Endo + Epi). For each animal DFTs were determined in a balanced random order for the 3 configurations. Ventricular fibrillation was induced by pacing (30 Hz, 8 V, for 5 seconds). DFT was accurately measured with the up/down procedure until 3 reversal of defibrillation success or failure occurred. DFTs (mean +/- SD) were extracted and compared using paired t test and analysis of variance. RESULTS: DFTs were 14.6 +/- 11.0 J for Endo and significantly decreased (p < 0.01) when an additional SQ (9.4 +/- 7.2 J) or epicardial patch (8.9 +/- 6.5 J) was added to endovenous lead, without significant difference between Endo + SC and Endo + Epi configurations. CONCLUSIONS: Regarding this important decrease of DFT (respectively -35% for Endo + SC and -39% for Endo + Epi), additional patches should be more often recommended in patients with low safety margin of DFT. In those cases subcutaneous patches should be preferred instead of epicardial patches. Moreover, an additional reason to recommend this attitude could be the possible generator batteries saving.

Valvular replacement for aortic stenosis on patients in NYHA class III and IV. Early and long term results.

From January 1972 to June 1990, 112 patients between 39 and 83 years old, divided into 68 NYHA class III (60.72%) and 44 NYHA class IV, underwent surgery for aortic stenosis. There were 67 male (59.82%) and 45 female (40.18%). Early mortality included 8 patients (7.14%). Actuarial survival (including early postoperative mortality) for all 112 patients was 88.39%, 77.67%, 67.85% and 65.7% t one year, five, ten and fifteen years respectively. Clinical criteria are subjective but they remain the best prognostic factor. Surgery is indicated at occurrence of first symptoms, but, even in advanced cases, aortic valvular replacement can significantly improve survival and functional status. Even if operative risk is increased and secondary cardiomyopathy often progresses after surgery, aortic valve replacement results seem better than those of medical treatment alone.

[Thoracic aortic aneurysm in Marfan syndrome]. / Anévrysme de l'aorte thoracique dans la maladie de Marfan.

Thoracic aortic aneurysms are the main cardiovascular complication of Marfan's syndrome. Elastic tissue dystrophy of the ascending aorta is responsible for appearances of cystic medial necrosis in the major forms. Dilatation of the ascending aorta is progressive with time. The risk of dissection and rupture, an acute complication of Marfan's syndrome, is very high when the aortic dilatation reaches 60 mm, although dissection may be observed with dilatation of 50 mm. Aortic regurgitation is found in half the cases. Echocardiography, CT scan and MRI provide accurate assessment of the anatomy of the lesions and help in following up the dilatation. Betablocker therapy slows down the progression of the dilatation. Bentall's procedure was first described in 1968 with its technical variants for reimplantation of the coronary arteries: Cabrol's procedure, technique of periostal lean-to, the button technique, are major advances in the surgical treatment of ascending aortic aneurysms. The life expectancy is reported to be about 90% at 5 years and 75 to 80% at 10 years. Reoperation is sometimes necessary because of pseudo-aneurysms occurring as a late complication at the operation site or because of other aneurysms developing. Progress in the field of genetics is a hope for the future.

[Heart valvular and coronary manifestations of Takayasu disease. Apropos of a surgically-treated case]. / Manifestations valvulaires et coronaires au cours d'une maladie de Takayasu. A propos d'un cas opéré.

Cardiac involvement in Takayasu's disease is well documented. This is often the result of severe hypertension. However, severe clinical manifestations of aortic regurgitation and coronary insufficiency are much less common. The authors report a case in which post-infarction angina and severe left ventricular failure led to a double valve replacement and an aorto-right coronary bypass graft procedure. The diagnosis of Takayasu's disease was suspected before surgery and was confirmed by histological examination.