Influence of HLA matching on survival in heart transplantation

BACKGROUND: In renal transplantation, the degree of HLA matching has been reported to be negatively correlated with graft loss, with the number of rejections with complications. This association is less clear in heart transplantation, where there are contradictory studies, although most are consistent with those in renal transplantation. The objective of this study was to analyze differences in the probability of survival and the incidence of complications during follow-up according to the degree of HLA-A, -B, and -DR matching. MATERIALS AND METHODS: Two hundred forty-three consecutive patients transplanted over a 13-year period were analyzed for age, gender, pretransplant factors associated with mortality, number of rejections and infections, incidence of acute graft failure, arterial hypertension, diabetes, and survival time with cause of death with reference to the number of HLA matches (zero to six). Exclusion criteria included retransplants, heart-lung transplants, pediatric transplants, and perioperative mortality. Groups were compared using the chi(2) and ANOVA (Bonferroni posthoc test) tests. Kaplan-Meier survival curves were compared using the log rank test. The significance level was set at P < .05. RESULTS: The overall probability of survival of our series at 1, 5, and 10 years was 85%, 77%, and 60%, respectively. HLA-A, -B, and -DR compatibility: No significant differences were found when the curves were compared (log-rank: .005). The best survival rates were obtained with lower degrees of matching. No significant differences were found in the number of rejections or infections, although survival rates (P = .007) were higher among those with the lower degrees of matching. CONCLUSIONS: A higher degree of HLA-A, -B, and -DR matching did not have a positive effect on heart transplant patient survival, rejection episodes or infections.     

Anti-HLA antibodies in heart transplantation

We have analyzed the relationship between the development of transplant-related coronary artery disease (TRCAD) and the following potential risk factors: (a). number of HLA mismatches between recipient and donor; (b). production of anti-HLA antibodies; (c). growth of lymphocytes infiltrating the graft; and (d). frequency of biopsy proven episodes of acute rejection. The study population consisted of 285 adult heart allograft recipients who were monitored over a period of two years or more. The results demonstrate a significant correlation between TRCAD, generation of anti-HLA class II antibodies and potential of lymphocytes infiltrating the graft to proliferate ex-vivo in medium containing IL-2. Humoral and cellular immune responses to HLA-DR antigens expressed by the graft seem to underlie the development of TRCAD.     

Myocyte growth in the failing heart

Adult ventricular myocytes can undergo mitotic division, resulting in an increase in the aggregate number of cells in the heart. The improvement in the methodological approach to the analysis of tissue sections by immunostaining and confocal microscopy has defeated the dogma that myocyte regeneration cannot occur in the adult heart. Most importantly, primitive and progenitor cells have been identified in the human heart. These cells express telomerase and have the capability of undergoing lineage commitment and rapid cell division, expanding significantly the contracting ventricular myocardium. These cell populations possess all the molecular components regulating the entry and progression through the cell cycle, karyokinesis, and cytokinesis. The recognition that myocyte hypertrophy and regeneration, as well as myocyte necrosis and apoptosis, occur in cardiac diseases has contributed to enhancing our understanding of the plasticity of the human heart.     

Reinfusion of mediastinal blood after heart surgery

BACKGROUND: Several authors studying autotransfusion of shed mediastinal blood in patients undergoing heart operations have published conflicting results regarding reduction of the need for homologous blood transfusion. The effect on coagulation parameters is also unclear. METHODS: In a prospective randomized study, 198 patients who underwent coronary artery bypass grafting or a valvular operation were divided into 2 groups: a group with autotransfusion of shed mediastinal blood after an operation and a control group. Continuous reinfusion of mediastinal blood was done until no drainage was present or for a period of 12 hours after the operation. The amount of blood lost and autotransfused, the number of homologous blood products transfused, and the coagulation parameters were monitored. RESULTS: The number of patients requiring homologous blood transfusion was significantly different between the 2 groups (54/98 [55%] in autotransfused patients vs 73/100 [73%] in the control group, P =.01). The number of re-explorations for excessive bleeding was similar in the 2 groups (7/98 [7.1%] vs 8/100 [8%]), but the amount of blood collected postoperatively was higher in the autotransfused patients compared with control patients (1200 +/- 201 mL vs 758 +/- 152 mL, P =.0007). Coagulation parameters analyzed and complication rates were similar in the 2 groups after the operations. CONCLUSION: Autotransfusion of shed mediastinal blood reduces the need for homologous blood transfusion in patients undergoing various cardiac operations. The cause of increased shed blood in patients undergoing autotransfusion remains unclear.     

Valvular heart disease

Reoperation for valvular heart disease has been associated with a higher operative mortality than primary operations, especially in patients who had multiple prior operations. We have analyzed the 226 consecutive patients who underwent valve replacement. These involved 163 primary operations, 52 first reoperation, and 11 second/third reoperations. Preoperative left ventricular dysfunction was more severe, and operation time and cardiopulmonary bypass time were significantly greater according to the number of operations, associated with a greater amount of intraoperative blood loss. The operative mortality after a second/third reoperation was 27.3%, which was significantly higher than that after primary operation (6.7%) (p < 0.05), and that after first reoperation (5.8%) (p < 0.05). Seven (64%) patients who underwent a second/third reoperation had poor preoperative left ventricular function (%FS < 25%), and 5 (71%) of these required postoperative mechanical supports, and 3 (60%) of the 5 patients died of low output syndrome. We have found that poor preoperative left ventricular function and the duration on cardiopulmonary bypass, but not the number of reoperation were correlated with operative mortality. Continued efforts should be directed to decrease the mortality for multiple reoperative valve surgery.     

Thymoglobuline use in pediatric heart transplantation.

The literature has few data regarding the use of polyclonal anti-thymocyte globulin in pediatric cardiac transplantation. We describe our single-center, retrospective study of the use of Thymoglobuline in a pediatric population. We included in the study 31 consecutive heart transplant recipients (mean age, 7.8 years; median age, 9 years; range, 4 months-17 years), who all survived surgery. To induce immunosuppression, all patients received Thymoglobuline therapy at age-dependent doses (1-1.5 mg/kg/day between 0 and 1 year; 1.5-2 mg/kg/day from 1 year to 8 years; and 2.5 mg/kg/day >8 years). Duration of treatment was 1 to 7 days. In patients <1 year, the total number of lymphocytes was maintained at >500/mm(3). Thirty of 31 patients are alive at the end of follow-up. During the first 3 months, 3 Grade 3A and 10 Grade 1A (Working Formulation grading system) rejection episodes occurred. All reversed after steroid treatment. Eleven viral infections, 2 bacterial infections, and 1 fungal infection occurred. Not all patients with infection were symptomatic but all responded successfully to treatment. One episode of post-transplantation lymphoproliferative disease regressed after decreasing immunosuppression therapy and after acyclovir therapy. At the end of follow-up, 19 patients are without steroids. Immunosuppression therapy with Thymoglobuline is safe in the pediatric age group if the number of lymphocytes is monitored strictly.     

Viability of autologous fascia lata in heart valve replacements

A histological and radioautographic examination of 11 autologous fascia lata heart valves used in man is described. There was a significant decrease, exponential with time, in the number of fibroblasts per unit volume (P<0·001). The collagen bundles were grossly disorganized and separated, suggesting a breakdown of the cross-linkage in the tissue. Redundant connective tissue on the surface of the valve cusp became oedematous and contained many trapped cells. A pseudoendothelium was formed within 10 days. Incorporation of tritium-labelled thymidine in the nuclei of the fibroblasts showed a sixfold reduction over 9 to 12 weeks following implantation, suggesting a failure of metabolism in these cells. The suitability of fascia lata for human heart valve replacement is discussed.     

Suturing of penetrating wounds to the heart in the nineteenth century: the beginnings of heart surgery

The beginnings of cardiac surgery go back to the 19th century. This article describes the history of the first attempts to operate on the heart. In 1882, Dr Block from Danzig, and in 1895, Simplicio Del Vecchio, published reports of animal experiments showing that the suturing of heart wounds is possible. After unsuccessful attempts by Axel Cappelen in Norway and Guido Farina in Italy, it was Ludwig Rehn of Germany who first sutured a laceration of the right ventricle of a human heart. Shortly afterward, Antonio Parrozzani successfully sutured a stab wound of the left ventricle. Following cardiac surgery back to its very beginnings, it is striking that the first attempts in the 19th century to repair the injured heart were regarded with great skepticism, and that heart suturing only slowly became an established method of treatment. Once the concept of cardiac surgery had become accepted, however, many kinds of operations were developed, paving the way for an explosion in the number of cardiac operations, as we well know, in the century that followed.     

Education of heart failure patients

Therapeutic patient education (TPE) has proved to be beneficial in a number of chronic diseases such as diabetes, asthma, chronic kidney failure. A TPE unit has been set up in Marie-Madeleine hospital in Forbach. In order to improve the actions carried out with patients with heart failure undergoing treatment, a satisfaction survey was carried out with this group of patients.     

The use of marginal heart beating donor livers for transplantation in the United kingdom

BACKGROUND: This study investigated the use of deceased heart-beating donor livers offered for transplantation during a 10-year period, during which there has been an increasing disparity between organ supply and demand in the United Kingdom. METHODS: Summary data from the National Transplant Database were analyzed on all 7107 heart-beating cadaveric donor livers offered for transplantation in the United Kingdom between 1996 and 2006, with particular attention to livers that were not retrieved, not transplanted, or that subsequently failed to function after transplantation. RESULTS: The difference between the number of patients registered for liver transplantation in the United Kingdom and those transplanted increased from 132 in 1996 to 333 in 2006, leading to a 77% increase in the number of waiting list deaths. Mean donor age increased by 6.1 (5.7-6.6) years during the period studied, in part because of a reduction in the proportion of donors arising from road fatalities. Despite this, the rate of primary nonfunction remained low (1.7% during 1996-2006). The absolute risk increase of primary nonfunction arising from receipt of a moderately as opposed to mildly steatotic organ was 2.6%, which translates to a "number needed to harm" of 41 patients. CONCLUSIONS: The decline in both the number and the quality of livers offered for transplantation in the United Kingdom during the past 10 years has not been associated with a change in the rate of primary nonfunction. In these times of acute donor shortage, these data may justify a more liberal use of marginal grafts.     

Surgery in heart and lung transplant patients

BACKGROUND: Heart and lung transplantation is an increasingly successful procedure. After transplant, these patients may need surgery for common diseases and for problems caused by immunosuppression. The purpose of this study was to determine surgical outcomes heart and lung transplant patients after transplantation. METHODS: All patients in the cardiopulmonary transplant registry were reviewed. Data collected included sex, age at transplantation, age at subsequent procedure, number and type of surgical procedures performed, number and type of postoperative complications, grade of complications (using the Clavien classification), and outcome (discharge to home, disabled, dead). RESULTS: During a 15-year period, 222 (64%) of 345 heart or lung transplant patients underwent a surgical procedure. Seven hundred fifty-four procedures were performed (median 3 procedures/patient). Sixty-seven patients suffered 72 complications (10% complication rate). Twenty-one (29%) complications were grade I; 20 (28%) were grade IIA; 21 (29%) were grade IIB; 8 (11%) were grade III; and 2 (3%) were grade IV. Twelve percent of the complications in the heart transplant patients were cardiac in nature, whereas 0% of the complications in the lung transplant patients were pulmonary in nature. There were 475 (63%) discharges to home, 2 (0.2%) inpatient deaths, and 18 (2%) deaths within 30 days; 49 (7%) procedures resulted in disability; and 210 (28%) patients were lost to follow-up. CONCLUSIONS: Heart or lung transplant patients will frequently need subsequent surgical procedures. Overall, the patients tolerated the procedures well, and the morbidity and mortality rates were acceptable. Most complications were not related to the transplanted organ.     

Determinants of waiting time for heart transplants in the United States.

BACKGROUND: Reports have been published on factors affecting the variations in waiting times for kidney and liver transplant candidates who have been registered on the United Network for Organ Sharing's waiting list. This study reports on determinants of waiting time differences that occur in the eleven UNOS regions for heart transplant candidates. METHODS: Retrospective analysis of 11,345 primary heart waiting-list registrations and 15,868 cadaveric donors, from whom 7,043 hearts were recovered and transplanted for the years 1994-96. Because estimated populations in the eleven UNOS regions vary from 10.8 to 43.2 million, analyses utilized Registrations/million population and Transplants/million population to obtain an R/T ratio. The relationship of the R/T ratio to the median waiting time was then examined for different demographic variables. RESULTS: The numbers of new heart candidate registrations, heart transplants performed, and waiting list deaths have undergone little change from 1991 through 1996. National median waiting times varied by basic demographic variables such as ABO blood type, race, age group, and UNOS medical urgency status. In the eleven UNOS regions, registrations per million ranged from 11.5 to 33.0 and transplants per million from 5.3 to 10.7. Registration/Transplant ratios correlated with median waiting times for urgency Status 1 and 2 as well as for blood group O recipients. Correlation with blood type AB recipients was less consistent, in part, due to the small number of AB recipients. CONCLUSIONS: There are wide variations in the number of heart transplant candidate registrations and in the number of heart transplants performed in the eleven UNOS regions. The registration to transplantation ratio correlated with median waiting times in these regions. Factors possibly contributing to the observed variations were examined.     

Therapy of heart failure

The incidence and prevalence of heart failure is on the rise. It has become the single most expensive health care item in the United States and the number one discharge diagnosis in the elderly. The goals of therapy include both prevention and treatment of heart failure. In recent years research studies and randomized clinical trials have revolutionized the understanding of the pathophysiology and treatment of this disease. This article focuses on the medical management of chronic systolic heart failure based on the pathophysiology of the disease. Systolic heart failure is characterized by a decrease in left ventricular function and cardiac output, which results in activation of several neurohormonal compensatory systems. The long term effects of this neurohormonal activation leads to further deterioration of cardiac function. The use of hydralazine and nitrates to reduce the systemic vascular resistance was the first to show an improvement in mortality and morbidity. Then angiotensin converting enzyme inhibitors, by inhibiting the renin angiotensin system, demonstrated a greater improvement in mortality and morbidity. More recently the inhibition of the sympathetic stimulation with beta-blockers has been shown to have an additive effect on morbidity and mortality in combination with angiotensin-converting enzyme inhibitors. Digoxin and diuretics remain important for improving symptoms and decreasing hospitalizations but have not been shown to decrease mortality. The most recent advance in the treatment of cardiac failure is the demonstration that the aldosterone antagonists, spironolactone decreases morbidity and mortality.     

Implications for vigilance of a method for evaluating patterns of change in heart rate during anaesthesia

Instantaneous heart rate was recorded in five patients and analysed for change in rate using the criterion of percentage variation either side of the starting rate with resetting throughout the anaesthetic each time the permitted variation was exceeded. The number of occasions on which change occurred was counted, the patterns of change were analysed and the effect of two sampling methods (six-second sample and six-second average) on these patterns was compared. A large number of patients (131) was investigated using the six-second sampling method and the number of changes and patterns of change were evaluated. It is suggested that the six-second sampling technique, combined with the 10 or 15% variation, may be useful for the evaluation of vigilance, and has implications for the design of monitoring apparatus in the future.     

Prognostic significance of ventricular ectopic beats in chronic ischaemic heart disease

Holter studies were performed periodically over a period of up to 7 years (mean 33 months) in 175 post-myocardial infarction patients. According to the number of ventricular ectopic beats (VEBs), the patients were classified into two main groups: those with few VEBs, i.e. less than 8 per hour, and those with many, i.e. 8 or more per hour. By comparing the number of ectopic beats during the different monitoring sessions, it was found that individual patients tended to remain in their originally allocated groups. Patients with frequent VEBs were more likely to die suddenly, the difference being significant (P < 0,001). No association could be demonstrated between recurrent non-fatal myocardial infarction and ectopic beat frequency (P > 0,10).     

Diabetes and heart

Diabetics are subjects to a high cardiovascular risk. This concept is now accepted by all and has been demonstrated in clinical practice by the constantly increasing number of diabetic cardiac patients and cardiac diabetics. The many therapeutic trials carried out on the prevention of cardiovascular complications in diabetics have made it possible to define therapeutic goals. HbA1c must be less than 6.5%. Target blood pressure values are 130/80 mmHg or even 125/75 in the case of renal insufficiency. If conventional treatments have proven efficacy against stroke and coronary events, only molecules which modulate the renin-angiotensin-aldosterone system provide additional nephroprotection in diabetics. However, single-agent therapy is seldom sufficient to achieve glycaemic or blood pressure targets. Diabetic dyslipidemia also requires attentive management, usually by a statin, with a target LDL cholesterol < 1 g/l at the onset of microalbuminuria. All these measures should make it possible to obtain a significant reduction in the cardiovascular risk of diabetic patients.     

The association of scoliosis and congenital heart defects.

The effects of cardiac surgery on patients with congenital heart defects and the subsequent development of scoliosis were studied. A group of 998 patients with congenital heart defects who were less than sixteen years old were operated on at the Mayo Clinic during the ten-year period 1950 through 1959. Standing roentgenograms of the spine were made of 377 of the patients ten years or more after surgery. The ages of the patients at follow-up ranged from ten years and seven months to thirty-five years and three months, with a mean age of twenty-one years and four months. The average length of follow-up was fourteen years and eleven months. Of the 377 patients, thirty-two (8.5 per cent) had curves greater than 20 degrees. The female:male ratio of patients with congenital heart defects was 1:1, whereas of those who developed scoliosis it was 5:3. There was no correlation between scoliosis and the following: patient's sex, cardiac abnormality, size or side of the heart, side of the aortic arch, presence of cyanosis, age at surgery, number and type of surgical incisions, number and side of ribs removed, or number and type of surgical procedures.     

Risks of combined surgical treatment of acquired heart valve defects and coronary heart disease

In the past years the number of patients with combined treatment of the heart valves and coronary arteries rised as well as the patients age did. In 1980-1987 the rate of patients with aortic valve replacement and simultaneous aorto-coronary bypass was 10.9% in those who underwent aortic valve replacement and 2.9% in those who had aorto-coronary bypass operation. Since 1988 the ratios changed to 18.2% and 4.9%. For the calculation of the operative risk of the combined operative treatment (AVR + CABG, MVR + CABG) we compared these groups with those patients with isolated operations (MVR, AVR, CABG). We studied all patients during 1980 and July 1989. The hospital mortality of combined procedures was significantly increased. The mortality among female patients was higher as compared to the male group. The age of patients treated by the combined procedures was higher as compared to the isolated procedures. The mean age of the patients which died was severely increased as compared to the isolated procedures. However, in the combined procedures this increase was not as pronounced as in the isolated groups. Patients with combined procedures had a higher NYHA class. The risk factors of the combined procedures were comparable to isolated CABG.     

Influence of induction therapy on rejection and survival in heart transplantation

BACKGROUND AND AIMS: Immunosuppressive therapy has undergone great changes in recent years as a result of the introduction of new drugs, presumed a prior to be more effective and better tolerated. The greatest advance seems to have been the introduction of interleukin-2 (IL-2) receptor antagonists. The objective of this study was to determine whether the use of IL-2 receptor antagonists in induction therapy has implications for the development of rejection and survival. MATERIALS AND METHODS: Three hundred sixty-five consecutive cardiac transplant patients who received induction therapy were included. Heart-lung and transplants in children under 10 years were excluded. Three groups were compared according to the induction therapy (OKT3, 10 days; OKT3, 7 days; and IL-2R antagonists). Each treatment corresponded to a time period: OKT3 10 days from June 1989 to April 1994; OKT3 7 days from May 1994 to October 2002; and IL-2R antagonists from November 2002 to May 2004. Baseline characteristics of recipient and donor, surgical times, postsurgical complications, maintenance immunosuppression, number of rejections, time (days) to first rejection, and probability of survival at 1 year were recorded. We used analysis of variance, chi(2) test, Kaplan-Meier curves, and log-rank test as appropriate. A P-value < .05 was considered significant. RESULTS: There were significant differences in the characteristics of the transplanted patients in the various time periods. Thus, recipients in the OKT3 10 day group had worse status but better donors, whereas recipients in the IL-2R antagonists group had better status but older donors with longer duration of ischemia. The incidence of acute graft failure was similar in the three groups. The number of rejection episodes in the first year was higher among the OKT3 groups (OKT3 10 days, 1.7 +/- 1.3; OKT3 7 days, 1.2 +/- 1.2; IL-2R antagonists, 1.0 +/- 1.2; P = .02) and the probability of survival at 1 year was also lower (OKT3 10 days, 74%; OKT3 7 days, 77%; IL-2R antagonists, 94%; P = .0007). CONCLUSIONS: Induction therapy with IL-2 antagonists offers important advantages over treatment with OKT3 in terms of survival, with absolute and relative risk reductions of 20% and 27%. Furthermore, it did not increase the number of rejections, although this may have been due to the greater use of MMF versus azathioprine.