[Cardiac transplantation; results after 5 years]. / La transplantation cardiaque; résultats après 5 ans.

After cardiac transplantation, long-term results were assessed in a group of 46 patients who survived more than 5 years after surgery. They were the survivors (50%) of a group of 92 patients who underwent transplantation before January 1990. On January 1995, mean follow-up was 82 +/- 14 months. Quality of life was estimated satisfactory (mean score 8.4 +/- 2); 60% of the patients were active; 89% were class NYHA I or II. Nevertheless, several problems have been identified: rise in body weight for all, over 10 kg in 31%; hypertension, renal failure, considered to be severe (serum creatinine > 250 micrograms/l) in 26%, diabetes in 13%, osteoarthropathy in 33%, cancer in 6%, and, above all, chronic alteration of the coronary arterial bed in 53% of the patients. These problems reflect the immunological conflict and complications of immuno-suppression.

Early impairment of acetylcholine-induced endothelium-dependent coronary vasodilation is not predictive of secondary graft atherosclerosis.

STUDY OBJECTIVE: To test the hypothesis that the magnitude of early constriction of coronary arteries to acetylcholine might be a useful predictor of secondary graft atherosclerosis. DESIGN: The responses of epicardial coronary arteries to stepwise intracoronary infusion of acetylcholine (10(-8)M to 10(-5)M) were compared in 7 control subjects and in 18 patients who had undergone transplants within 2 months after surgery. MEASUREMENTS AND RESULTS: Vessel dimensions (percent basal diameter) were measured by quantitative angiography. Follow-up at 1 year showed angiographically normal coronary arteries in 12 patients (group 1) and coronary atherosclerosis in 6 patients (group 2). In control subjects, acetylcholine induced a dose-dependent dilation from 10(-8)M to 10(-6)M. No significant variation was observed at 10(-5)M. In patients with transplants early after surgery, diameters did not vary significantly from base at 10(-8)M in either group and constricted significantly at higher concentrations. Vasodilator responses to intracoronary isosorbide dinitrate were similar in both groups with transplants early after surgery, and at 1 year in group 1, but significantly lower than in control subjects. CONCLUSIONS: In patients who had undergone transplants, acetylcholine-induced endothelium-dependent coronary artery dilation is similarly impaired early after surgery (within 2 months) in patients with and without coronary atherosclerosis at 1-year follow-up. Thus, response to acetylcholine is not a predictor of secondary atherosclerosis in patients with heart transplants.

[Cardiac surgery in chronic hemodialysed patients: immediate and long-term results]. / Chirurgie cardiaque chez l'hémodialysé chronique: résultats immédiats et à long terme.

Between 1979 and 1993, 50 patients (33 men and 17 women) receiving chronic haemodialysis, underwent 53 cardiac surgical procedures in the department. The mean age was 56 +/- 13 years. The average duration of preoperative dialysis was 82 +/- 63 months. The average duration of cardiac symptoms before surgery was 35 +/- 52 months. Twenty-seven patients (54%) were in NYHA functional classes III or IV before surgery. Sixteen patients (32%) had preoperative left ventricular ejection fractions of less than 0.40. Twelve patients (24%) were emergency referrals. Twenty-nine patients underwent isolated coronary bypass surgery, 13 patients underwent isolated aortic valvular replacement which had to be repeated in one case, 3 patients underwent mitral valve replacement, which had to be repeated in 2 cases, and 5 patients underwent combined surgery. The average aortic clamping time was 75 +/- 32 minutes, the average cardio-pulmonary bypass time was 125 +/- 50 minutes. The surgical revascularisation of the coronary patients was incomplete in 37% of cases because of the severity of the underlying coronary artery disease. The average postoperative bleeding was 800 +/- 650 ml; 29 patients (58%) were transfused with an average of 4.3 +/- 3 units of blood. The global early mortality was 9 patients (18%); 10% in coronary bypass, 7% in aortic valve replacement and 50% in patients with more complex procedures. The causes of death were cardiac (n = 4), sepsis (n = 2) and multiple organ failure (n = 3). The morbidity was 39%, mainly due to low cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

[Cardiac transplantation. Operative risk factors]. / La transplantation cardiaque. Facteurs de risques opératoires.

An evaluation of the risks of heart transplantation, and in particular operative risk factors, should lead to optimal decision making in light of the lack of sufficient supply of transplantable organs. The optimal recipient for transplantation is the patient who will benefit best from the organ in terms of survival and quality of life and for whom the operative risk is the smallest. This study emphasized the preparing role of donors over 45, the poorer prognosis in recipients over 60, the situations limited by pulmonary resistance and the notion of retransplantation. The practical impact of these observations is of prime importance.

Donor/recipient aorta size mismatch in heart transplantation: a technical alternative.

A technical alternative is proposed to enable transplantation in cases of considerable size mismatch between donor and recipient aorta: interposition of a Dacron graft of intermediate diameter. This procedure was performed in a 56-year-old patient weighing 75 kg in whom a heart from a 40-kg donor was implanted.

[Coronary reoperations: indications and results]. / Réinterventions coronaires: indications et résultats.

The aim of this study was to assess the results of coronary reoperations and to determine the indications. Between January 1972 and December 1990, 166 coronary reoperations were performed in 161 patients (5 patients were operated three times). The interval between the first and second operation was 93 +/- 46 months. The interval between recurrence of symptoms and reoperation was 27 +/- 40 months. Recurrence of symptoms was related to isolated problems with the bypass grafts in 23% of cases, to an aggravation of the coronary disease without problems with the bypass grafts in 17% of cases and to an association of the two conditions in 60% of cases. Mortality in the first 30 postoperative days was 7.8% (13/161). The predictive factors of mortality were age over 70 years and an interval between recurrence of symptoms and reoperation of over 12 months. The causes of death were myocardial infarction (n = 5), left ventricular failure (n = 4), sudden death (n = 3), and arrhythmias (n = 1). The average follow-up period of survivors (n = 134) was 40 +/- 32 months. Four patients have been transplanted. Seven patients died secondarily. The cause of death was cardiac in 4 cases and non-cardiac in 3 cases. The actuarial 5 year and 10 year survival rates were 85 +/- 3%. Actuarial absence of myocardial infarction, angina, Class III-IV cardiac failure and transplantation was 87 +/- 4% at 5 years and 69 +/- 10% at 10 years. These figures show that coronary reoperation gives good functional results and long-term survival.(ABSTRACT TRUNCATED AT 250 WORDS)

[Aprotinin in cardiac surgery in patients with platelet anti-aggregant treatment]. / L'aprotinine en chirurgie cardiaque chez les patients sous antiagrégants plaquettaires.

A large number of coronary patients referred for coronary bypass surgery receive platelet anti-aggregant therapy which has the disadvantage of increasing per and postoperative haemorrhage. The aim of this study was to assess the effects of aprotinin in 60 patients under platelet antiaggregant therapy (aspirin 250 mg/day) for over 30 days before surgery for coronary bypass grafting. The clinical (age, weight, diagnosis, bypass time, number of grafts) and biological features (preoperative haemoglobin concentration, platelet count and fibrinogen levels) were identical in a group treated by aprotinin (Group A, n = 30) and a control group (Group B, n = 30). The aprotinin treatment protocol was an intravenous injection of 2 million KIU (kallikrein inhibitory units) before starting the cardiopulmonary bypass and 2 million KIU in the filling liquid of the bypass circuit. A significant reduction in blood loss was observed in Group A with respect to Group B (370 +/- 154 ml versus 651 +/- 323 ml at day 1, p < 0.01). The haemoglobin concentration was higher in Group A than in Group B (11.9 +/- 1.6 g/100 ml versus 10.3 +/- 1.4 g/100 ml, p < 0.001) and fewer patients required blood transfusion (Group A: 16% versus Group B: 43%, p = 0.04). In conclusion, high doses of aprotinin given to patients on aspirin therapy undergoing coronary bypass surgery, significantly reduce postoperative blood loss and the number of patients transfused.

Effects of plasma lipid levels on blood distribution and pharmacokinetics of cyclosporin A.

The present study attempted to characterize the distribution of cyclosporin A (CsA) among the lipoprotein fractions, very-low-, intermediate-, low-, and high-density (VLDL, IDL, LDL, and HDL, respectively) in the plasma of patients awaiting heart transplantation and the influence of plasma lipid constituents on the pharmacokinetics of CsA. Major fractions of a therapeutic concentration of CsA were found in HDL and in LDL. In addition, plasma lipid concentrations (total cholesterol, triglycerides, phospholipids, VLDL-cholesterol--TC, TG, PL, VLDLc, respectively) are positively correlated with the CsA distribution within the LDL fraction, and negatively correlated with the CsA distribution within the HDL fraction. Thus, the percentage of CsA in each type of lipoproteins was shown to vary with the lipid levels among individuals. A significant negative correlation was found between apparent distribution volume at steady state (Vss) in plasma and TC, PL, and LDLc and between the area under the curve measured in blood (AUCB) for whole blood and PL.

Acetylcholine-induced constriction of angiographically normal coronary arteries is not time dependent in transplant recipients. Effects of stepwise infusion at 1, 6, 12 and more than 24 months after transplantation.

OBJECTIVES: The aim of this study was to evaluate whether acetylcholine may be a useful tool for detection of early angiographically undetectable coronary atherosclerosis in heart transplant recipients. BACKGROUND: Coronary artery disease is the main determinant of long-term prognosis in transplant recipients. Acetylcholine-induced constriction of angiographically normal coronary arteries in heart transplant recipients could be due to early atherosclerosis, and acetylcholine has been proposed for early detection of coronary artery disease. METHODS: The responses of large coronary arteries to stepwise intracoronary infusion of acetylcholine (10(-8) to 10(-5) mol/liter) were compared in five control subjects and in four groups of transplant recipients 1, 6, 12 and > 24 months postoperatively (group 1, n = 6; group 2, n = 7; group 3, n = 6; group 4, n = 6, respectively). All patients had normal coronary arteriographic findings. Vessel dimensions were measured in four segments in each patient. RESULTS: In control subjects, acetylcholine increased diameters significantly at 10(-8), 10(-7) and 10(-6) mol/liter (all p < 0.001 vs. basal value). No significant variation was observed at 10(-5) mol/liter. Intracoronary isosorbide dinitrate increased diameters of all segments (p < 0.001). In transplant recipients, vessel diameters did not vary significantly from baseline at 10(-8) and 10(-7) mol/liter concentrations in groups 1 and 3 and at 10(-8) mol/liter in group 4. Vessels constricted significantly in all the other cases. Comparisons of each group with control subjects showed that responses were significantly different for all concentrations but 10(-8) mol/liter in groups 3 and 4. Intracoronary isosorbide dinitrate elicited coronary vasodilation similar to that of control subjects in all groups of transplant recipients. CONCLUSIONS: This study indicates that the acetylcholine response is persistently abnormal in transplant recipients compared with that in normal control subjects and that this abnormality may not be related simply to the presence of atherosclerosis. Thus, acetylcholine may not be a useful tool for early detection of coronary atherosclerosis in heart transplant recipients.

Mitroflow pericardial valve: long-term durability.

Isolated aortic (n = 107), mitral (n = 63), and tricuspid (n = 1) valve replacement and 28 double-valve replacements were performed with a second generation of pericardial valves, the Mitroflow valve, in 199 patients from March 1983 to December 1986. Follow-up (total, 1,058 patient-years) was extended to 106 months and 91.5% complete. Mean age was 58 +/- 13 years. The operative mortality included 22 deaths, non-cardiac-related in 7. The actuarial probability of survival for all patients was 66% +/- 4% at 8.5 years. There were no significant differences between patients with aortic valve replacement, mitral valve replacement, or double-valve replacement. The rate of thromboembolic events, antithromboembolic therapy-related hemorrhage, periprosthetic leak, and endocarditis is extremely minimal. Structural valve dysfunction occurred at a rate of 3.2% +/- 0.5%/patient-year. Actuarial freedom from the event was 94.6% +/- 1.7% at 5 years and 63.7% +/- 6.5% at 8.5 years for all valves. There were no difference in structural valve dysfunction rate between patients having aortic, mitral, or double-valve replacement. Thirty-five patients were reoperated on (3.4 +/- 0.6%/patient-year for all). The rate of all valve-related morbidity and mortality was 5.6% +/- 0.7%/patient-year for all patients, actuarial freedom from the event being 44% +/- 7% at 8.5 years. These data suggest that the excellent hemodynamic characteristics of the valve are balanced by a risk of valve failure that is slightly increased when compared with porcine valves.

Preservation of the aortic valve in acute aortic dissection: long-term echocardiographic assessment and clinical outcome.

The aim of the present study was to determine the long-term status of the native aortic valve after surgical treatment of acute aortic dissection involving the ascending aorta. From 1972 to 1991, 93 patients underwent operation for type I or II aortic dissection. There were 76 men and 17 women. Mean age was 54 +/- 13 years. Eighty patients (86%) had a conservative procedure regarding the aortic root and aortic cusps: 74 had prosthetic replacement of the ascending aorta and 6, complete replacement of the aortic arch. Thirteen patients (14%) had simultaneous replacement of the aortic valve and the ascending aorta. The overall hospital mortality rate was 29% (27/93). The overall actuarial survival rate was 60.2% +/- 5.2%, 49.7% +/- 6.1%, and 35.9% +/- 8.1% at 5, 10, and 15 years, respectively. The survival rates for patients who had an ascending aortic procedure only were 63% +/- 5.5%, 54% +/- 6.5%, and 39% +/- 8.5% at 5, 10, and 15 years, respectively, and for patients who required aortic valve replacement, 45% +/- 14% and 22% +/- 17.5% at 5 and 10 years, respectively. Fifty long-term survivors (94% follow-up) with preservation of the aortic valve and aortic root were studied. Among them, 9 (18%) died within a mean interval of 97 +/- 46 months after operation. Causes of death were ischemic cardiac failure (2), aortic rupture or extension of dissection (4), renal disease (1), stroke (1), and sudden death (1). Forty-one patients had long-term clinical and echocardiographic evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Preservation of the aortic valve in acute dissection of the ascending aorta]. / Préservation de la valve aortique dans les dissections aiguës de l'aorte ascendante.

The aim of this study was to evaluate the status of the native aortic valve in patients operated for acute dissection of the ascending. aorta (ADAA). Between November 1972 and November 1991, 93 patients were operated for ADAA. There were 76 men and 17 women (average age 54 +/- 12 years). The aortic valve was reserved in 80 cases (86%). In 13 patients (14%) aortic valve replacement was associated with replacement of the ascending aorta. The early mortality was 29% (27/93). The global actuarial survival rates at 5, 10 and 15 years were 60.2 +/- 5.2%, 49.7 +/- 6.1% and 26.9 +/- 9.9% respectively. Fifty patients (94%) in whom the native aortic valve was preserved were followed up. Nine patients (18%) died and average of 97 +/- 46 months after surgery. The causes of death were aortic rupture or extension of the dissection (N = 4), ischemic cardiac failure (N = 2), renal failure (N = 1), cerebrovascular accident (N = 1) and sudden death (N = 1). Forty one patients underwent transthoracic echocardiography. Seven patients developed severe aortic regurgitation, 6 of whom had to be reoperated for aortic valve replacement. Echocardiography showed absence of of minimal aortic regurgitation in 22 cases and mild aortic regurgitation with normal left ventricular function in 12 cases (in 2 cases, aortic valve replacement was associated with surgical treatment of another valvular lesion or of coronary artery disease). Therefore, aortic valve replacement was performed in 8 patients 61.5 +/- 51.2 months after the initial operation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Simultaneous heart and kidney transplantation using the same donor]. / Transplantations cardiaques et rénales simultanées utilisant le même donneur.

From 1988 to 1991, five cases of combined heart and kidney transplantation using the same donor have been achieved at our institution. All patients were males, 58 +/- 6 (46 to 64). The cardiac condition leading to the cardiac replacement was a dilated cardiomyopathy in one case, end-stage ischemic disease in 3, and failure of a previous cardiac transplantation in one. The renal condition claiming for a graft was a Glomerular nephritis in one, a polycystic disease in 3, and renal failure due to CyA toxicity in one; chronic hemodialysis was mandatory in all patients but one. There were no hospital deaths. The five patients are current survivors, the mean follow-up being 22 +/- 10 months (2-50 months). Five rejection episodes occurred in three patients; two patients have never demonstrated any cardiac rejection. All but one recovered a normal renal function as soon as the 7 th post operative day; only one episode of renal rejection has been detected, easily reversed by corticoids. No simultaneity was ever observed between cardiac and renal rejection episodes. Thus, the detection of rejection must be carried out separately for each graft organ. In four patients, cineangiograms of the coronary vessels were done respectively 12, 30 and 50 months post operatively and revealed a normal coronary bed. Thus, combined heart and kidney transplantation seems to be a realistic approach in properly selected patients in whom cardiac and renal failures cannot be treated by more conventional procedures.

Pharmacological bridge to cardiac transplantation: current limitations.

Addition of intravenous enoximone to sympathomimetic agents permits a rapid and drastic improvement in the clinical and hemodynamical condition of patients in cardiogenic shock referred for a mechanical bridge to transplantation. The present experience, based on the management of 52 patients, permits us to point out the current limitations of this pharmacological bridge: the rate of sudden death, the incompleteness of the physical rehabilitation of the patients, and the vanishing effect of intravenous enoximone.

Effects of time and previous acute rejection episodes on coronary vascular reserve in human heart transplant recipients.

OBJECTIVES: This study examined whether previous rejection episodes may have deleterious effects on coronary vascular reserve of heart transplant recipients months after transplantation. BACKGROUND: Coronary reserve has been demonstrated to be within the normal range in long-term transplant patients without previous episodes of rejection. Conversely, acute rejection is associated with a dramatic reduction of coronary reserve, which is rapidly restored after therapy. METHODS: Coronary flow velocity was measured by intracoronary Doppler catheter before and after a maximally vasodilating dose of intracoronary papaverine in 16 control subjects and in 59 transplant patients classified into three groups with respect to time after transplantation: 1 to 6 months (group 1, n = 17), 7 to 18 months (group 2, n = 22) and > 18 months (group 3, n = 20). Coronary vascular reserve was evaluated through peak/rest coronary flow velocity ratio and minimal coronary vascular resistance index. All patients had normal findings on left ventricular angiography and coronary arteriography and a normal left ventricular mass. RESULTS: Arterial pressure was normal in all groups. Heart rate in the three groups of transplant patients, mean aortic pressure in groups 1 and 2, left ventricular systolic pressure in group 2 and rate-pressure product in groups 1 and 2 were higher than in control subjects. Average number of rejection episodes per patient was similar in the three groups of patients (group 1, 2.4 +/- 1.4; group 2, 2.5 +/- 1.9, and group 3, 2.1 +/- 1.3). Results showed no difference between each group of transplant patients and control subjects for peak/rest coronary flow velocity ratio (control subjects, 5.2 +/- 0.8; group 1, 5.3 +/- 1.5; group 2, 4.9 +/- 1.2, and group 3, 4.4 +/- 1.6) and for minimal coronary vascular resistance index (control subjects, 0.18 +/- 0.03; group 1, 0.18 +/- 0.04; group 2, 0.20 +/- 0.06, group 3, 0.23 +/- 0.11). In addition, patients with zero or one rejection episode had similar values of peak/rest coronary flow velocity ratio and minimal coronary vascular resistance index (4.3 +/- 1.3 and 0.23 +/- 0.10, respectively, n = 22) as did those with one or two rejection episodes (5.1 +/- 1.5 and 0.19 +/- 0.07, respectively, n = 24), and those with four or more episodes (5.2 +/- 1.4 and 0.19 +/- 0.05, respectively, n = 13). CONCLUSIONS: This study showed that coronary vascular reserve remains within normal range and is independent from the number of previous episodes of rejection until late after transplantation in human heart transplant patients with angiographically normal coronary arteries.

[Can solid state Holter monitoring replace endomyocardial biopsy in patients with heart transplantation?]. / Le Holter à mémoire solide peut-il remplacer la biopsie endomyocardique chez le transplanté cardiaque?

Acute cardiac graft rejection after transplantation, the diagnosis of which is based on the findings of endomyocardial biopsy, is associated with a reduction in coronary reserve due to abnormalities of the microcirculation. But this reduction in coronary reserve cause silent myocardial ischaemia (SMI)? In order to assess the frequency of SMI and ventricular arrhythmias during rejection, 53 consecutive Holter recordings were performed in 32 patients (28 men, 4 women, average age 47 +/- 11 years) 11 months after transplantation and within 24 hours of endomyocardial biopsy. The recorder which was used (Monitor One TC) analysed the ST segment in 2 leads in real time: ST segment depression of more than 1 mm lasting over 40 ms, 0.08 s after the J point were considered to be diagnostic of myocardial ischaemia. Although the frequency of SMI is low and not specific for cardiac rejection, its duration was twice as long (80 mn vs 38 mn) in this condition. On the other hand, ventricular arrhythmias are common in cardiac rejection and correlated with its severity according to Billingham's classification (VES p = 0.045; doublets p = 0.035; non-sustained VT p = 0.006).

Evaluation of direct effects of enoximone on systemic and pulmonary vascular bed in animals with a Jarvik total artificial heart.

Enoximone, a phosphodiesterase inhibitor, has positive inotropic and vasodilating actions. To evaluate specific effects of this drug on the systemic and pulmonary vascular bed, we administered enoximone as a 10-minute intravenous bolus at two different doses of 2 and 3 mg/kg of body weight, at different days, to five Holstein calves with a Jarvik 7-70 ml total artificial heart (Symbion, Inc., Salt Lake City, Utah). The calves were monitored for aortic pressure, right atrial pressure, pulmonary arterial pressure, and left atrial pressure. For each experiment cardiac output was maintained constant, and systemic and pulmonary vascular resistances were calculated at 0, 15, 30, and 60 minutes and every hour for 8 hours after infusion. Statistical analysis used analysis of variance and the paired t test with Bonferroni's correction. Data showed the following: (1) a marked systemic vasodilating action of enoximone at peak effect at 30 minutes with a 20% decrease in systemic vascular resistance from baseline value under constant cardiac output, returning progressively to normal values throughout the 8 hours; (2) a comparable effect for the two separate doses tested; (3) no specific action on the pulmonary vascular bed with "nonunidirectional" changes in pulmonary vascular resistance. This model was validated by the infusion of prostaglandin I2 in the same animals, at different days, which significantly decreased pulmonary vascular resistance of 50% at peak effect, under constant cardiac output. In summary, enoximone showed a proper systemic vasodilating effect with no specific action on the pulmonary vascular bed in an animal model of the total artificial heart. Decrease in pulmonary vascular resistances obtained with enoximone in clinical practice seems more related to the inotropic properties of the drug. Enoximone should not be administered in pulmonary hypertension, as suggested before.

[Emergency aorto-coronary bypass after myocardial infarction]. / Pontages aorto-coronaires en urgence au décours de l'infarctus aigu du myocarde.

During a recent three-year period, 37 patients had an emergent aortocoronary bypass (ACB) after evolutive acute myocardial infarction. The patients are divided up into two groups: group I includes 12 patients who were operated after the failure of early thrombolysis; group II includes 25 patients operated after the failure of revascularization through percutaneous angioplasty. In group I, all patients survived and 9 had no postoperative complications. In group II, the outcome was favorable for 16 patients. Long-lasting postoperative inotropic support was required for nine patients. Two patients died early. In all patients of the study, surgery failed to prevent myocardial necrosis but there was no recurrence of angina nor major left ventricular malfunction in the long term. This work suggests that early surgery after acute myocardial infarction may be a rescue procedure, with low risks and good long-term results.