Trends in patient selection for heart transplantation.

OBJECTIVES: The purpose of this study was to review specific outcomes of patient referrals and the utility of selection criteria for heart transplantation at a single transplant center and to assess important trends over a 5-year period. BACKGROUND: Although patient selection criteria are important for the clinical success of heart transplantation and the optimal utilization of the limited supply of donor organs, there are few data regarding actual outcomes and whether selection criteria are facilitating the identification of the most appropriate patients. METHODS: We retrospectively reviewed 511 consecutive referrals of adult patients with heart failure from January 1, 1987 to December 31, 1991. Patients were followed up to one of five end points: 1) acceptance onto the transplant waiting list, 2) rejection from the transplant waiting list, 3) death, 4) referral to another program, and 5) still pending evaluation. RESULTS: Of the 511 referred patients, 221 (43%) were accepted onto the waiting list, 222 (43%) were rejected, 39 (8%) died before the evaluation was completed, 15 (3%) were referred to another program and 14 (3%) are still pending evaluation. The rates for acceptance and rejection each year ranged between 30% and 51% and there were no consistent trends in the acceptance/rejection ratio from 1987 to 1991. Of the 221 patients accepted onto the waiting list, 115 (52%) underwent transplantation, 50 (22%) died, 12 (5%) were removed from the list because of clinical improvement, 9 (4%) were referred to another program and 35 (16%) are still on the waiting list. The continuing shortage of donor organs resulted in a marked increase in the size of the waiting list from 12.6 patients in 1987 to 36.5 in 1991, as well as a marked increase in the time on the waiting list before transplantation. Over 5 years, 50 patients were considered "too well" for transplantation (23% of all rejections). Of these 50 patients, 43 (86%) are alive and 7 were lost to follow-up during a mean period of 28.6 months (range 4 to 62). All 12 patients who were taken off the active transplant list because of improvement in symptoms, ejection fraction or peak exercise oxygen consumption are alive with a mean follow-up period of 27.7 months (range 11 to 61). CONCLUSIONS: These data confirm the fact that transplant referrals are a selected group of patients with a high mortality rate, as 8% died before the evaluation could be completed and 22% died while waiting for a suitable donor organ. Furthermore, patient selection criteria are able to identify a small subset of patients with a low mortality risk as patients who were rejected because they were too well or taken off the list for clinical improvement have a reasonably good prognosis.

Prostaglandins and cell-mediated immunity. The role of prostaglandin E1 in the induction of host-versus-graft and graft-versus-host reactions in mice.

Based on studies in lymphocyte cultures it has been suggested that endogenous prostaglandins (PG), especially those of the E series (PGE), suppress cell-mediated immune reactions during their induction phase. We have tested this theory in experimental animals using local host-versus-graft (HVG) and graft-versus-host (GVH) reactions in mice. These reactions were suppressed in a dose-dependent manner by treatment of the animals with PGE1. If, however, endogenous PGE was neutralized through treatment of the animals with immune sera directed against PGE (APSE1) then inhibition of the development of HVG and GVH reactions was seen. This inhibition could be abrogated in "add back" experiments by treatment of the animals with PGE1. We suggest that the action of PGE1 during the induction phase of CMI responses is governed by a bell-shaped dose-response curve with a response-enhancing effect at low PGE1 and a suppressive effect at high PGE1 concentrations. APSE1 has proved to be very effective in inhibiting responses, and thus treatment with anti-PG antibodies may not only represent a valuable tool for the study of the role of PG in immunoregulation, but may become useful in therapeutic interventions with the immune system--e.g., after bone marrow transplantation.

Management of acute right heart failure after combined heart and kidney transplantation: case report.

Combined heart and kidney transplantation is performed rarely and merits unique fluid-management considerations postoperatively. We present the case of a young man who developed acute right heart failure after combined heart and kidney transplantation and responded to hemofiltration. We believe that the postoperative management of combined heart and kidney transplant recipients should not be different from that of patients receiving a heart transplant only. Intravenous fluids should be administered judiciously, and hemofiltration should be instituted early to remove fluid and reduce preload if right heart failure develops.

Stage I adenocarcinoma presenting in the pneumonectomy specimen at the time of single lung transplantation.

Two patients at our institution underwent single lung transplantation. The procedure and the patient's postoperative course were uncomplicated in each case. Pathological examination of each pneumonectomy specimen revealed a well-differentiated adenocarcinoma; both were less than 1 cm in size. The remainder of each lung showed no evidence of adenocarcinoma and all lymph nodes were negative. Work-ups for an occult malignancy before and after surgery were negative. This is believed to be the first report of a single lung transplant in a patient with a primary adenocarcinoma of the lung. The implications and management of these patients are discussed.

Combined laser phototherapy and growth factor treatment of bronchial obstruction after lung transplantation.

Lung transplantation has resulted in dramatic functional improvement in patients with end-stage pulmonary diseases. Among the complications of lung transplantation are dehiscence and stenosis at the site of the bronchial or tracheal anastomosis. In this case report, we describe a single lung transplant recipient in whom partial bronchial dehiscence, followed by exuberant growth of granulation tissue, resulted in obstruction of the bronchial lumen. After mechanical dilation failed to produce lasting relief of bronchial obstruction, a novel approach to this problem was successfully employed: YAG laser phototherapy was used to remove obstructing granulation tissue, followed by application of a preparation derived from autologous blood platelets to promote epithelialization of the bronchial anastomosis. The bronchus remains patent and fully epithelialized six months after therapy.

Pulmonary function after successful heart transplantation. One year follow-up.

Congestive heart failure (CHF) has been associated with the development of restrictive ventilatory abnormalities and decreased pulmonary diffusing capacity. Whether these physiologic changes reflect permanent alterations of lung anatomy or result solely from potentially reversible alterations of lung water is not known. To examine this issue, we reviewed the pulmonary function tests (PFTs) and cardiac catheterization data from recipients of successful heart transplants prior to and 1 year after transplantation. Thirty-eight patients met the inclusion criteria (median age, 52 years). The median duration of symptomatic CHF prior to transplantation was 22 months (range, 3 to 72 months). After transplantation, spirometry revealed an improvement in FEV1 from 75.8 +/- 3.5 to 99.1 +/- 2.8 percent of predicted and FVC from 81.3 +/- 3.7 to 101.6 +/- 3.0 percent of predicted (p < 0.001). The FEV1/FVC ratio remained unchanged at 80 percent. Nonsmokers and former smokers had similar improvements in spirometry after transplantation. The TLC improved from 91.1 +/- 3.3 to 105.5 +/- 2.9 percent of predicted (p < 0.001); this improvement was due to an increase in inspiratory capacity. Diffusing capacity for carbon monoxide was decreased before transplantation and showed a small decline after transplantation from 82.3 +/- 3.2 to 76.8 +/- 2.6 percent of predicted (p < 0.05). After correction of severe CHF by cardiac transplantation, normalization of FEV1, FVC, and TLC can be anticipated. Diffusing capacity, however, may actually decline after transplantation.

Pediatric heart transplantation: results of 2- and 5-year follow-up.

Pediatric heart transplantation has become an accepted method of treatment for certain pediatric heart disease. From July 1986 to January 1993, we performed 25 orthotopic pediatric heart transplantations at the University of Minnesota Hospital and Clinics in 16 male patients and nine female patients. The average age was 8.5 years with a range from 7 days to 18 years. Three of the patients were younger than 1 year of age. The indications for transplantation included congenital heart disease in six patients and cardiomyopathy in 19 patients. Four of the patients with congenital heart disease had previously undergone a cardiac surgical procedure. Two patients with cardiomyopathy had mechanical assist devices in place at the time of transplantation. Donor age ranged from 2 months to 36 years. The donor organ ischemic time ranged from 60 minutes to 329 minutes, with an average of 191 minutes. Follow-up ranged from 6 to 84 months. Overall, there were seven deaths (28%) in the patients undergoing transplantation. Of the seven deaths, four (16%) were early (within 30 days) and three (14.3%) were late. The four early deaths were a result of donor organ failure, and the three late deaths a result of acute rejection. The 2-year survival for patients with a minimum 24-month evaluation was 79% (15 of 19). Of 12 patients available for 5-year assessment, 75% (9 of 12) were alive and doing well at the time this article was written. Pediatric heart transplantation can provide good intermediate and long-term survival for selected pediatric patients.

Outcome after referral for pediatric transplantation.

Although heart, heart-lung, or lung transplantation is performed in more than 200 children annually, the number of patients referred for such procedures is considerably greater, and little is known about the outcome of those referrals. To determine the outcome of pediatric transplant referrals we reviewed the follow-up of 31 patients evaluated at our institution for heart (24), heart-lung (three), or lung (four) transplantations between January 1991 and September 1992. Indications included hypoplastic left heart syndrome (seven patients), cardiomyopathy or myocarditis (seven patients), and postoperative congenital heart disease (10 patients) for heart transplantation; Eisenmenger's syndrome (three patients) for heart-lung transplantation; and primary pulmonary hypertension (two patients), broncho pulmonary dysplasia, and cystic fibrosis for lung transplantation. Only 14 of 31 referred patients were listed for transplantation; the remaining 17 patients either improved when medical therapy was maximized (nine patients), died within days of referral (three patients), refused (two patients), chose alternate surgery (one patient), were medically unacceptable (one patient), or are currently undecided (one patient). To date 7 of 14 patients listed have undergone successful heart transplantation; the remaining seven patients either improved and did not require transplantation (two patients), refused (one patient), died waiting (one patient), are currently awaiting a donor (one patient), or underwent Norwood procedure because of donor unavailability (two patients). Thus including patients who died before listing, only 14 of 31 referrals (45%) were deemed in need of a transplant.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood flow to the latissimus dorsi muscle pouch during chronic counterpulsation stimulation.

The cyclic contraction of a skeletal muscle ventricle (SMV) stimulated in counterpulsation results in phasic perfusion of the muscle. Perfusion will occur primarily during cardiac systole when the muscle is relaxed. However, the resting preload of the SMV will be systolic arterial pressure, which will impede blood flow to the relaxed muscle. To determine the effect of chronic counterpulsation stimulation on the blood flow to an SMV and identify stimulation regimens that prevent the risk of chronic ischemia, SMVs were created in four mongrel dogs by implementing an implantable mock circulation device. The SMV was stimulated in counterpulsation for 4 weeks after a 2-week vascular delay period and 2 weeks of low-frequency muscle conditioning. During biweekly studies, the muscle was stimulated in four modes against preloads varying from 20 to 120 mm Hg. Resting blood flow decreased significantly at preloads greater than 60 mm Hg. Normalized blood flow increased between 10% and 30% during stimulation; greater increases corresponded to more demanding stimulation modes. The elevated blood flow during stimulation, however, decreased with increasing preload. Stroke work increased with increasing preload until preload exceeded 100 mm Hg. The decreased blood flow and increased stroke work occurring at higher preloads indicate that the supply/demand ratio becomes compromised with increasing preload. A hyperemic response occurred during the resting beats after a stimulated beat, increasing the volume blood flow by as much as 80%. This response occurred regardless of preload or stimulation rate. If the SMV relaxed before the onset of systole, a hyperemic response occurred within the stimulated beat.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac xenografting in the pig-to-rhesus monkey model: manipulation of antiendothelial antibody prolongs survival.

Transplantation of immediately vascularized grafts across species barriers in which preformed cytotoxic antibodies exist, otherwise known as discordant combinations, has uniformly resulted in hyperacute rejection. We studied how well plasma exchange and perfusion through organs removes preformed immunoglobulin M cytotoxic antibodies and prolongs survival of a porcine heart heterotopically transplanted into a rhesus monkey. With the use of plasma exchange or absorption of antibodies by porcine kidney perfusion with or without immunosuppression, graft survival was prolonged, although antibody-mediated rejection ultimately occurred. In one case in which plasma exchange, kidney perfusion, and immunosuppression were combined, a functioning pig heart survived in a rhesus monkey for 8 days without evidence of rejection. The animal was killed on day 8 according to protocol because of a wound dehiscence. With this animal we were able to demonstrate that circulating antibodies against graft endothelium had bound to the graft endothelium without inducing rejection, a process referred to as accommodation. In this case, despite the presence of antiendothelial antibodies, complement did not appear to be activated, and fibrin thrombi did not form. Although we have achieved this rejection-free survival only in one animal, this case suggests that it may be possible to maintain xenotransplants in discordant species without rejection if preformed antibodies are appropriately lowered or altered during the initial period of graft implantation.

Single lung transplantation for severe emphysema.

UNLABELLED: Lung transplantation is effective therapy for patients with severe obstructive lung disease. We reviewed seven patients with severe emphysema (age, 48 +/- 5 years; forced expiratory volume in 1 second [FEV1] 0.76 +/- 0.26 liters) who received single-lung transplants (SLT) at our institution between August 1989 and September 1990. Studies to assess the adequacy of cardiac function before transplantation showed moderately reduced right ventricular function (by multiple gated acquisition, 34 +/- 6%), moderately elevated pulmonary artery pressure (25 +/- 3 mm Hg), and normal left ventricular function (by multiple gated acquisition 65% +/- 12%) and coronary arteriograms. Time on the waiting list before transplantation was reduced compared with heart-lung transplant (HLT) recipients (waiting time, 2.9 +/- 1.5 months for SLT, 9.6 +/- 10.2 months for HLT). Six of the SLT recipients are currently alive (after transplantation interval, 17 +/- 5 months); the remaining recipient died of pulmonary embolism 21 days after SLT. Number of ventilator days, intensive care unit days, and days to hospital discharge after transplantation did not differ significantly from HLT recipients. Cardiopulmonary bypass was necessary in four SLT recipients. Pulmonary function was markedly improved after SLT (FEV1, 1.78 +/- 0.73 L/min after SLT versus 0.75 +/- 0.3 L/min before SLT; p less than 0.01), and functional status is correspondingly improved. CONCLUSIONS: SLT constitutes effective therapy for patients with severe emphysema, including those with moderate reduction of right ventricular function; and SLT offers distinct advantages over HLT, including decreased waiting time before transplantation, improved donor organ utilization, and less frequent need for cardiopulmonary bypass.

Abdominal complications after lung transplantation.

BACKGROUND: Serious abdominal complications after heart and heart-lung transplantation have been a well-documented source of morbidity and mortality in this patient population. This report reviews the incidence and spectrum of abdominal complications occurring in lung transplant recipients at a single institution. METHOD: Between January 1988 and July 1993, 75 patients underwent lung transplantation (58 single lung, 16 bilateral single lung, and 1 double lung) at the University of Minnesota. RESULTS: Twelve patients (16%) sustained 20 abdominal complications. There were 11 early abdominal complications (< or = 30 days after transplantation) including prolonged adynamic ileus (4), diaphragmatic hernia after omental wrap (3), ischemic bowel (2), colitis with hemorrhage (1), and splenic injury after colonoscopy (1). There were nine late abdominal complications (range, 32 days to 28 months after transplantation) including colonic perforation (4), cholelithiasis/choledocholithiasis (2), development of a mesenteric pseudoaneurysm (1), fungal hepatic abscess (1), and intraabdominal hemorrhage (1). Twenty-six procedures were performed for management of the abdominal complications including: colonoscopy (7), colectomy (5), repair of diaphragmatic hernia (3), colostomy takedown (4), small-bowel resection (2), open cholecystectomy with common bile duct exploration (1), open cholecystectomy (1), splenectomy (1), mesenteric arterial pseudoaneurysm embolization (1), and percutaneous liver biopsy (1). Four patients died of causes attributable to their abdominal complications. CONCLUSIONS: In each case in which a death occurred, there was a delay between the onset of symptoms and diagnosis and intervention of more than 6 days. Abdominal complications accounted for 22% of all deaths in our lung transplantation group. A high index of suspicion and early recognition and intervention will decrease the morbidity and mortality caused by abdominal complications in lung transplant patients.

Primary cardiac lymphoma treated with orthotopic heart transplantation: a case report.

Primary lymphoma of the heart is an extremely rare tumor. It is associated with a high mortality rate because of the advanced stage of myocardial involvement at initial presentation. Conventional surgical and medical treatments have not met with much success. This article reports the first case of primary cardiac lymphoma treated with orthotopic heart transplantation. The patient had hemodynamically significant severe acute rejection, neutropenic sepsis, and tumor recurrence during the late postoperative period, illustrating the difficulties associated with concomitant immunosuppression and tumor chemotherapy. Unfortunately, the patient died after a period of remission. Our approach to the integration of immunosuppression with chemotherapy, posttransplantation follow-up, and complications is discussed.

Congenital bronchopulmonary foregut malformations. Intralobar and extralobar pulmonary sequestrations communicating with the foregut.

Two unusual variants of bronchopulmonary foregut malformations are presented. The first case was that of a 12-year-old male with a history of pectus excavatum in whom severe lobar emphysema developed secondary to an intralobar pulmonary sequestration that communicated with the esophagus. This case was unusual in that foregut communications and associated congenital anomalies are generally believed to be restricted to extralobar pulmonary sequestrations. The second case was that of a 27-year-old woman with an extralobar pulmonary sequestration that communicated with the esophagus. The sequestration was unusual in that it arose in the anterior mediastinum and received the bulk of its blood supply from the pulmonary artery. The occurrence of mixed forms of pulmonary sequestrations supports the hypothesis that extralobar and intralobar sequestrations and sequestrations with foregut communication are related thoracic disorders that are best considered bronchopulmonary foregut malformations.

Conservative management of postoperative chylothorax using somatostatin.

Chylothorax is a rare but serious postoperative complication of thoracic surgical procedures. We report the case of a 77-year-old man who underwent a coronary artery bypass procedure using a left internal mammary artery pedicle graft. A permanent pacemaker was required postoperatively. A persistent postoperative chylothorax developed necessitating continuous drainage and conservative management. Somatostatin was instituted when after 1 week this management failed to resolve the chylothorax. This led to rapid cessation of chyle production. Enteral feeding was reinstituted without complication and surgical intervention was avoided.

Adjunctive coronary endarterectomy: improved safety in modern cardiac surgery.

BACKGROUND: Advances in cardiac surgery have led to an improved safety record for coronary endarterectomy. METHODS: We retrospectively reviewed the cases of 64 patients who underwent adjunctive coronary endarterectomy between August 1988 and February 1992. There were 44 men, and the mean age was 65 years. Forty-one patients (64%) had sustained a previous infarction. Overall, endarterectomy was performed on 76 vessels, and the right coronary system was involved in 46 (61%). RESULTS: The postoperative infarction rate was 5%. Incomplete occlusion ( < 90% stenosis) of the endarterectomized vessel significantly increased the risk of infarction (p < 0.05). There were two early deaths (3%). The mean follow-up was 46 months. Clinically, 91% of the survivors were angina free, and 80% had no symptoms of heart failure at the time of follow-up. Left ventricular function had improved in 36% of those restudied (5/14). A total of 17 recatheterizations were done at a mean interval of 19 months after operation. The endarterectomy graft patency rate was 80% (16/20) compared with 78% (28/36) for conventional grafts ( p = not significant). The actuarial survival rates were 89% and 71% at 1 year and 5 years, respectively. A history of previous infarction was significantly associated with higher long-term mortality (p < 0.02). CONCLUSIONS: Overall, these results demonstrate that in modern cardiac surgery, coronary endarterectomy is safer than previously thought and can be used effectively to achieve complete revascularization in selected patients.

A "designer" annuloplasty ring for patients with massive mitral annular dilatation.

We describe a new type of mitral annuloplasty ring designed for use in the massively dilated mitral annulus. The ring can be fabricated at the operating table from a 4-mm Gore-Tex graft and umbilical tape and can be adapted in size to fit a mitral annulus of any diameter.

Noninvasive diagnosis of cardiac allograft rejection in an orthotopic canine model.

BACKGROUND: A decline in the R wave voltage obtained from surface electrocardiograms once correlated with cardiac allograft rejection. With cyclosporine therapy, however, these electrocardiographic findings became inconsistent, occurring only during severe rejection episodes. Despite cyclosporine use, intramyocardial unipolar peak-to-peak amplitudes obtained from plunge electrodes are reported to be highly sensitive and specific for diagnosing rejection. These reports are based on heterotopic grafts, which atrophy over time, making long-term voltage changes during rejection difficult to interpret. The purpose of this study was to use analysis of unipolar peak-to-peak amplitudes as a prospective monitoring tool for diagnosing orthotopic cardiac allograft rejection. METHODS: Ten adult mongrel dogs underwent orthotopic heart transplantation with the attachment of four intramyocardial leads. The unipolar peak-to-peak amplitudes were measured daily and compared with endomyocardial biopsy results. RESULTS: We found that intramyocardial unipolar peak-to-peak amplitude analysis had a sensitivity and a specificity of 100% for diagnosing rejection. We also found that as the number of myocardial leads increased, the sensitivity of detecting rejection also increased. CONCLUSIONS: We conclude that unipolar peak-to-peak amplitude analysis is an accurate noninvasive means for early detection of cardiac allograft rejection in an orthotopic model. Its success should allow less frequent, more selective use of endomyocardial biopsy.

Conformational adaptation of muscle: implications in cardiomyoplasty and skeletal muscle ventricles.

In dynamic cardiomyoplasty and other forms of muscle-powered cardiac assist, the stretch that should be applied to the skeletal muscle to obtain optimal resting tension remains unclear. To test the hypothesis that skeletal muscle is capable of conformational adaptation over time, the effect of altered resting tension on the chronic performance of a skeletal muscle ventricle was studied. In 7 mongrel dogs, skeletal muscle ventricles constructed from the lastissimus dorsi muscle were stimulated to contract for 12 weeks against an implantable mock circulation. The preload pressure was altered, thereby varying the resting tension of the latissimus dorsi. One group (group I; n = 5) was maintained at a preload of 80 mm Hg, whereas a second group (group II; n = 2) was maintained at 20 mm Hg. Adaptation to preload was observed. After 12 weeks, the pressure increase generated by the skeletal muscle ventricle at a preload of 20 mm Hg was only 35 +/- 2 mm Hg for group I compared with 44 +/- 5 mm Hg for group II. At a preload of 80 mm Hg, the pressure increase was 61 +/- 4 mm Hg for group I and only 34 +/- 6 mm Hg for group II. Adaptation of the latissimus dorsi to a new resting tension has important implications in the use of skeletal muscle for cardiac assist. Stretching the latissimus dorsi to its in situ length during cardiomyoplasty is not required for future muscle performance to be optimal.

Liberalization of donor criteria in lung and heart-lung transplantation.

Since March 1986, we have performed 26 heart-lung transplantations, 42 single-lung transplantations, 9 bilateral single-lung transplantations, and 1 double-lung transplantation. The original lung donor requirements were as follows: age less than 40 years, no smoking history; no gram-negative rods or fungus on sputum Gram stain; arterial oxygen tension greater than 140 mm Hg on an inspired oxygen fraction of 0.40; no infiltrate or pneumothorax on the chest radiograph; and donor height within 15 cm (6 inches) of recipient height. As the number of potential recipients increased, so did the waiting time. To counter this delay, during the past year we have liberalized our donor criteria. We now accept lung donors up to age 60 years. Any kind of smoking history is acceptable unless there is chronic obstructive pulmonary disease or pulmonary fibrosis on the chest radiograph. Sputum must be free from fungus, but gram-negative rods are treated with appropriate antibiotics. The arterial oxygen tension on an inspired oxygen fraction of 0.40 should be greater than 100 mm Hg, and a small pulmonary infiltrate is not worrisome. This liberalization of the donor pool for lung and heart-lung transplantation has not adversely affected early outcome.