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Heart-lung transplantation: successful therapy for patients with pulmonary vascular disease.

: We report our initial experience with three patients who received heart-lung transplants. The primary immunosuppressive agent used was cyclosporin A, although conventional drugs were also administered. In the first patient, a 45-year-old woman with primary pulmonary hypertension, acute rejection of the transplant was diagnosed 10 and 25 days after surgery but was treated successfully; this patient still had normal exercise tolerance 10 months late. The second patient, a 30-year-old man, underwent transplantation for Eisenmengers syndrome due to atrial and ventricular septal defects. His graft was not rejected, and his condition was markedly improved eight months after surgery. The third patient, a 29-year-old woman with transposition of the great vessels and associated defects, died four days postoperatively of renal, hepatic, and pulmonary complications. We attribute our success to experience with heart-lung transplantation in primates, to the use of cyclosporin A, and to the anatomic and physiologic advantages of combined heart-lung replacement. We hope that such transplants may ultimately provide an improved outlook for selected terminally ill patients with pulmonary vascular disease and certain other intractable cardiopulmonary disorders.

Clinical experience, complications, and survival in 70 patients with the automatic implantable cardioverter/defibrillator.

Seventy patients received the automatic implantable defibrillator, five original devices and 72 modified second-generation devices using only bipolar rate sensing and delivering an R wave synchronous cardioverting/defibrillating shock, for either ventricular tachycardia or fibrillation. The primary clinical arrhythmia was sustained ventricular tachycardia in 32 patients, ventricular fibrillation in 20 patients, and both ventricular tachycardia and fibrillation in 18 patients. Before implantation of the device the patients had survived 3.1 +/- 2.3 arrhythmic episodes, including 1.9 +/- 1.7 cardiac arrest, and had received 4.0 +/- 2.1 antiarrhythmic drugs without improvement. Sixty-eight patients ultimately received devices. After a follow-up period of 8.9 +/- 7.7 months (range 1 to 33), 37 patients received a total of 463 discharges. Inability to determine the precise reason for most discharges and the unpleasant nature of the discharges were the major clinical problems encountered. Complications included postoperative death (one patient), lead problems (six patients), inadequate energy requiring explanation (two patients), and pocket infection (one patient. Life-table analysis revealed 6 and 12 month cardiovascular survival of 95.0% and 89.9% and sudden death survival of 98.2%. In our experience, survival with the automatic implantable cardioverter/defibrillator exceeds that with other forms of therapy.

Treatment of patients with aortic dissection presenting with peripheral vascular complications.

The Incidence of peripheral vascular complications in 272 patients with aortic dissection during a 25-year span was determined, as was outcome after a uniform, aggressive surgical approach directed at repair of the thoracic aorta. One hundred twenty-eight patients (47%) presented with acute type A dissection, 70 (26%) with chronic type A, 40 (15%) with acute type B, and 34 (12%) with chronic type B dissections. Eighty-five patients (31%) sustained one or more peripheral vascular complications: Seven (3%) had a stroke, nine (3%) had paraplegia, 66 (24%) sustained loss of a peripheral pulse, 22 (8%) had Impaired renal perfusion, and 14 patients (5%) had compromised visceral perfusion. Following repair of the thoracic aorta, local peripheral vascular procedures were unnecessary in 92% of patients who presented with absence of a peripheral pulse. The operative mortality rate for all patients was 25% ± 3% (68 of 272 patients). For the subsets of individuals with paraplegia, loss of renal perfusion, and compromised visceral perfusion, the operative mortality rates (± 70% confidence limits) were high: 44% ± 17% (4 of 9 patients), 50% ± 11% (11 of 22 patients), and 43% ± 14% (6 of 14 patients), respectively. The mortality rates were lower for patients presenting with stroke (14% ± 14% [1 of 7 patients]) or loss of peripheral pulse (27% ± 6% [18 of 66 patients]). Mul-tivariate analysis revealed that impaired renal perfusion was the only peripheral vascular complication that was a significant independent predictor of Increased operative mortality risk (p = 0.024); earlier surgical referral (replacement of the appropriate section of the thoracic aorta) or more expeditions diagnosis followed by surgical renal artery revascularization after a thoracic procedure may represent the only way to Improve outcome in this high-risk patient subset. Early, aggressive thoracic aortic repair (followed by aortic fenestration and/or abdominal exploration with or without direct visceral or renal vascular reconstruction when necessary) can save some patients with compromised visceral perfusion; however, once visceral Infarction develops, the prognosis Is also poor. Increased awareness of these devastating complications of aortic dissection and the availability of better diagnostic tools today may Improve the survival rate for these patients In the future. The initial surgical procedure should Include repair of the thoracic aorta in most patients.

Impact of Prophylactic Immediate Posttransplant Ganciclovir on Development of Transplant Atherosclerosis A Post Hoc Analysis of a Randomized, Placebo-Controlled Study

BACKGROUND Coronary artery disease occurs in an accelerated fashion in the donor heart after heart transplantation (TxCAD), but the cause is poorly understood. The risk of developing TxCAD is increased by cytomegalovirus (CMV) infection and decreased by use of calcium blockers. Our group observed that prophylactic administration of ganciclovir early after heart transplantation inhibited CMV illness, and we now propose to determine whether this therapy also prevents TxCAD. METHODS AND RESULTS One hundred forty-nine consecutive patients (131 men and 18 women aged 48+/-13 years) were randomized to receive either ganciclovir or placebo during the initial 28 days after heart transplantation. Immunosuppression consisted of muromonab-CD3 (OKT-3) prophylaxis and maintenance with cyclosporine, prednisone, and azathioprine. Mean follow-up time was 4.7+/-1.3 years. In a post hoc analysis of this trial designed to assess efficacy of ganciclovir for prevention of CMV disease, we compared the actuarial incidence of TxCAD, defined by annual angiography as the presence of any stenosis. Because calcium blockers have been shown to prevent TxCAD, we analyzed the results by stratifying patients according to use of calcium blockers. TxCAD could not be evaluated in 28 patients because of early death or limited follow-up. Among the evaluable patients, actuarial incidence of TxCAD at follow-up (mean, 4.7 years) in ganciclovir-treated patients (n=62) compared with placebo (n=59) was 43+/-8% versus 60+/-10% (P<0.1). By Cox multivariate analysis, independent predictors of TxCAD were donor age >40 years (relative risk, 2.7; CI, 1.3 to 5.5; P<0.01) and no ganciclovir (relative risk, 2.1; CI, 1.1 to 5.3; P=0.04). Stratification on the basis of calcium blocker use revealed differences in TxCAD incidence when ganciclovir and placebo were compared: no calcium blockers (n=53), 32+/-11% (n=28) for ganciclovir versus 62+/-16% (n=25) for placebo (P<0.03); calcium blockers (n=68), 50+/-14% (n=33) for ganciclovir versus 45+/-12% (n=35) for placebo (P=NS). CONCLUSIONS TxCAD incidence appears to be lower in patients treated with ganciclovir who are not treated with calcium blockers. Given the limitations imposed by post hoc analysis, a randomized clinical trial is required to address this issue.

Infectious Complications in Heart Transplant Recipients Receiving Cyclosporine and Corticosteroids

The rate of infectious complications differed significantly in two groups of heart transplant recipients who received different immunosuppressive regimens. Compared with patients who received conventional immunosuppression, patients treated with cyclosporine had a lower rate of infectious complications, and the contribution of infection to observed mortality was lower. Herpes simplex virus caused less morbidity and there were fewer active cytomegalovirus infections in seropositive recipients treated with cyclosporine. The incidence of bacterial pulmonary infections and associated bacteremia also decreased impressively. A decrease in nocardial infections was offset by a rise in those due to Legionella species. The frequency of aspergillosis was decreased by 54% in the cyclosporine-treated group, but half of these infections disseminated beyond the lung and such dissemination was always fatal. Infections with Pneumocystis carinii were significantly less common with cyclosporine-based immunosuppression. Screening serologic tests for toxoplasma should be done routinely and consideration given to prophylaxis in heart transplant recipients at high risk.

Implantable electrical left ventricular assist systems: Bridge to transplantation and future

An implantable left ventricular assist system (LVAS) utilizing an electromechanically driven dual pusher-plate blood pump has been employed in a multiinstitutional trial as a bridge to cardiac transplantation. Under development for permanent circulatory support in patients with end-stage heart disease, the LVAS, in this application, derives power and control from an external console via a percutaneous lead. The LVAS was implanted in 20 patients (16 men, 4 women) who were hemodynamically unstable or in refractory cardiogenic shock. The mean age was 44.9 years (range, 25 to 63 years). Preoperative diagnosis was evenly divided between end-stage ischemic disease, cardiomyopathy, and acute myocardial infarction. Implanted in the left upper quadrant within the anterior abdominal wall, the blood pump was connected between the left ventricular apex and ascending aorta. Total support of the systemic circulation and substantial left ventricular unloading were achieved with synchronous counterpulsation for periods up to 90 days (mean, 22.7 days). All patients were stabilized hemodynamically. The mean preoperative cardiac index of 1.5 L/min/m2 increased by a factor of 2. Pulmonary arterial pressures decreased substantially. Serious complications occurred in 16 patients, precluding cardiac transplantation in 10. Most complications (greater than 70%) were in patients who did not receive transplants; the most common complication was bleeding. Twelve of 13 patients with LVAS implants for more than seven days were mobilized, and 4 were fully ambulatory and completely rehabilitated. Orthotopic cardiac transplantation was performed in 10 patients after implants ranging from two to 90 days (mean, 30.3 days).(ABSTRACT TRUNCATED AT 250 WORDS)

Significant reduction in the number of fungal infections after lung-, heart-lung, and heart transplantation using aerosolized amphotericin B prophylaxis

Since July 1993, amphotericin B (5 mg TID to be increased up to 20 mg TID within 5 days after surgery) has been given as inhalation throughout the posttransplant hospital stay. This group consists of 126 patients (mean age 39.8 years, 79 men, 47 women, 22 LTx, 27 HLTx, and 75 HTx). The incidence and spectrum of fungal infections were compared with a similar cohort of 101 patients (=control, mean age 40.0 years, 73 men, 28 women, 12 LTx, 12 HLTx, and 77 HTx) who were transplanted within a similar time period before introduction of ampho-prophylaxis. Both groups received the same triple-drug immunosuppressive protocol. The two groups were compared with regard to the spectrum of fungal, bacterial, viral, and protozoa1 infections as well as the incidence of acute rejection and level of renal function. The two-tailed f test was used to compare the linearized rate of events after the first 3 and 12 months, and the Gehan-test was used for statistical comparison of the actuarial incidence data in both groups.

A Reconsideration of Cerebral Perfusion in Aortic Arch Replacement

Ten patients underwent aortic arch replacement for aneurysmal disease from 1970 to 1985 using a simplified cardiopulmonary bypass (CPB) technique with partial brachiocephalic perfusion, low CPB flow (30 to 50 ml/kg/min), moderate systemic cooling (26 degrees to 28 degrees C), and topical hypothermic myocardial protection. The arterial line from a single pump head has a Y shape to perfuse the femoral artery (20F cannula) and either the innominate or left carotid artery (14F). Of the 10 patients (mean age, 58 years) with arch aneurysm (6 atherosclerotic, 2 dissections, and 2 degenerative), 3 had previously undergone major cardiovascular operations. Concomitant procedures included aortic valve replacement in 4 and coronary artery bypass grafting in 3. Eight patients survived the procedure, and 1 died three weeks after operation of a ruptured abdominal aneurysm. Among the survivors, CPB time was 119 +/- 36 minutes (+/- standard deviation), myocardial ischemia time was 79 +/- 32 minutes, and intraoperative blood requirement was 5.9 +/- 3.4 units. There were no postoperative strokes. Neurological complications were only minor and included an asymptomatic miosis and ulnar nerve paresthesias in 1 patient and transient vocal cord palsy in another. Applicable in most patients undergoing elective resection of degenerative and atherosclerotic arch aneurysms and in selected patients with arch dissections, this simplified technique of brachiocephalic perfusion without circulatory arrest provides an attractive and safe alternative; the potential advantages are technical simplicity, reduced CPB and operating times, and satisfactory cerebral protection.

Twenty-year clinical experience with porcine bioprostheses

BACKGROUND For the past 25 years, porcine valves have been the most widely implanted bioprosthesis, thereby becoming the standard for comparison with newer bioprosthetic valves. METHODS We retrospectively analyzed 2,879 patients who underwent aortic (AVR; n = 1,594) or mitral (MVR; n = 1,285) valve replacement between 1971 and 1990. Follow-up was 97% complete and extended to 20 years (total, 17,976 patient-years). Patient age ranged from 16 to 94 years; mean age in patients who underwent AVR was 60 +/- 15 (+/- standard deviation) years; that for patients who underwent MVR was 58 +/- 13 years. RESULTS The operative mortality rates were 7% +/- 1% (70% confidence limits) for AVR and 10% +/- 1% for MVR. Actuarial estimates of freedom from structural valve deterioration at 10 and 15 years were 78% +/- 2% (SE) and 49% +/- 4%, respectively, for the AVR subgroup; and 69% +/- 2% and 32% +/- 4%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from reoperation at 10 and 15 years were 76% +/- 2% and 53% +/- 4%, respectively, for the AVR subgroup and 70% +/- 2% and 33% +/- 4%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from thromboembolism at 10 and 15 years were 92% +/- 1% and 87% +/- 2%, respectively, for the AVR subgroup and 86% +/- 1% and 77% +/- 3%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from anticoagulant-related hemorrhage at 10 and 15 years were both 96% +/- 1% for the AVR subgroup and 93% +/- 1% and 90% +/- 2%, respectively, for the MVR subgroup (AVR > MVR; p < 0.05). Estimates of freedom from valve-related mortality at 10 and 15 years were 86% +/- 1% and 78% +/- 3%, respectively, for the AVR subgroup and 84% +/- 2% and 70% +/- 4%, respectively, for the MVR subgroup (p = not significant). Multivariate analysis (Cox model) showed younger age, later year of operation, and valve site (MVR > AVR) to be significant risk factors for structural valve deterioration. Younger age, later year of operation, valve site (MVR > AVR), and renal insufficiency were the significant, independent risk factors for reoperation. Multivariate analysis revealed that higher New York Heart Association functional class, longer cardiopulmonary bypass time, congestive heart failure, renal insufficiency, and longer cross-clamp time were significant risk factors for valve-related mortality. Valve manufacturer did not emerge as a factor in any analysis. CONCLUSIONS These long-term results with porcine bioprostheses were satisfactory, particularly in older patients and those undergoing AVR. As expected, younger age was a significant risk factor for structural valve deterioration and reoperation in both groups. Surprisingly, the durability of porcine bioprosthetic valves has not improved over time, which possibly can be attributed to more enhanced postoperative surveillance and earlier reintervention. These first-generation Hancock and Carpentier-Edwards porcine bioprostheses achieved similar long-term performance.

Wound healing complications with de novo sirolimus versus mycophenolate mofetil-based regimen in cardiac transplant recipients.

Sirolimus was introduced in de novo immunosuppression at Stanford University in view of its favorable effects on reduced rejection and cardiac allograft vasculopathy. After an apparent increase in the incidence of post‐surgical wound complications as well as symptomatic pleural and pericardial effusions, we reverted to a mycophenolate mofetil (MMF)‐based regimen. This retrospective study compared the outcome in heart transplant recipients on sirolimus (48 patients) with those on MMF (46 patients) in de novo immunosuppressive regimen. The incidence of any post‐surgical wound complication (52% vs. 28%, p = 0.019) and deep surgical wound complication (35% vs. 13%, p = 0.012) was significantly higher in patients on sirolimus than on MMF. More patients on sirolimus also had symptomatic pleural (p = 0.035) and large pericardial effusions (p = 0.033) requiring intervention. Logistic regression analysis showed sirolimus (p = 0.027) and longer cardiac bypass time (OR = 1.011; p = 0.048) as risk factors for any wound complication. Sirolimus in de novo immunosuppression after cardiac transplantation was associated with a significant increase in the incidence of post‐surgical wound healing complications as well as symptomatic pleural and pericardial effusions.