Potential Effect of Using ABO-Compatible Living-Donor Liver Transplantation

Liver transplantation increased 1.84-fold from 1988 to 2004. However, the number of patients on the waiting list for a liver increased 2.71-fold, from 553 to 1500. We used a mathematical equation to analyze the potential effect of using ABO-compatible living-donor liver transplantation (LDLT) on both our liver transplantation program and the waiting list. We calculated the prevalence distribution of blood groups (O, A, B, and AB) in the population and the probability of having a compatible parent or sibling for LDLT. The incidence of ABO compatibility in the overall population was as follows: A, 0.31; B, 0.133; O, 0.512; and AB, 0.04. The ABO compatibility for parent donors was blood group A, 0.174; B, 0.06; O, 0.152; and AB, 0.03; and for sibling donors was A, 0.121; B, 0.05; O, 0.354; and AB, 0.03. Use of LDLT can reduce the pressure on our liver transplantation waiting list by decreasing its size by at least 16.5% at 20 years after its introduction. Such a program could save an estimated 3600 lives over the same period.

Bone Marrow Mononuclear Cell Therapy Led to Alveolar-Capillary Membrane Repair, Improving Lung Mechanics in Endotoxin-Induced Acute Lung Injury

The aim of this study was to test the hypothesis that bone marrow mononuclear cell (BMDMC) therapy led an improvement in lung mechanics and histology in endotoxin-induced lung injury. Twenty-four C57BL/6 mice were randomly divided into four groups (n = 6 each). In the acute lung injur;y (ALI) group, Escherichia coli lipopolysaccharide (LPS) was instilled intratracheally (40 mu g, IT), and control (C) mice received saline (0.05 ml, IT). One hour after the administration of saline or LPS, BMDMC (2 x 10(7) cells) was intravenously injected. At day 28, animals were anesthetized and lung mechanics [static elastance (E(st)), resistive (Delta P(1)), and viscoelastic (Delta P(2)) pressures] and histology (light and electron microscopy) were analyzed. Immunogold electron microscopy was used to evaluate if multinucleate cells were type II epithelial cells. BMDMC therapy prevented endotoxin-induced lung inflammation, alveolar collapse, and interstitial edema. In addition, BMDMC administration led to epithelial and endothelial repair with multinucleated type II pneumocytes. These histological changes yielded a reduction in lung E(st), Delta P(1), and Delta P(2) compared to ALI. In the present experimental ALI model, the administration of BMDMC yielded a reduction in the inflammatory process and a repair of epithelium and endothelium, reducing the amount of alveolar collapse, thus leading to an improvement in lung mechanics.

Effects of Sleep Apnea on Nocturnal Free Fatty Acids in Subjects with Heart Failure

Study Objectives: Sleep apnea is common in patients with congestive heart failure, and may contribute to the progression of underlying heart diseae. Cardiovascular and metabolic complications of sleep apnea have been attributed to intermittent hypoxia. Elevated free fatty acids (FFA) are also associated with the progression of metabolic, vascular, and cardiac dysfunction. The objective of this study was to determine the effect of intermittent hypoxia on FFA levels during sleep in patients with heart failure. Design and interventions: During sleep, frequent blood samples were examined for FFA in patients with stable heart (ejection fraction < 40%). In patients with severe sleep apnea (apnea-hypopnea index = 15.4 +/- 3.7 events/h; average low SpO(2) = 93.6%). In patients with severe sleep apnea, supplemental oxygen at 2-4 liters/min was administered on a subsequent night to eliminate hypoxemia. Measurements and Results: Prior to sleep onset, controls and patients with severe apnea exhibited a similar FFA level. After sleep onset, patients with severe sleep apnea exhibited a marked and rapid increase in FFA relative to control subjects. This increase persisted throughout NREM and REM sleep exceeding serum FFA levels in control subjects by 0.134 mmol/L (P = 0.0038) Supplemental oxygen normalized the FFA profile without affecting sleep architecture or respiratory arousal frequency. Conclusion: In patients with heart failure, severe sleep apnea causes surges in nocturnal FFA that may contribute to the accelerated progression of underlying heart disease. Supplemental oxygen prevents that FFA elevation.

Ex Vivo Lung Perfusion: Early Report of Brazilian Experience

Introduction. Only about 15% of the potential candidates for lung donation are considered suitable for transplantation. A new method for ex vivo lung perfusion (EVLP) can be used to evaluate and recondition ""marginal,"" nonacceptable lungs. We have herein described an initial experience with ex vivo perfusion of 8 donor lungs deemed nonacceptable. Materials and Methods. After harvesting, the lungs were perfused ex vivo with Steen Solution, an extracellular matrix with high colloid osmotic pressure. A membrane oxygenator connected to the circuit received gas from a mixture of nitrogen and carbon dioxide, maintaining a normal mixed venous blood gas level in the perfusate. The lungs were gradually rewarmed, reperfused, and ventilated for evaluation through analyses of oxygenation capacity, pulmonary vascular resistance (PVR), lung compliance (LC), and biopsy. Results. The arterial oxygen pressure (with inspired oxygen fraction of 100%) increased from a mean of 206 mm Hg in the organ donor at the referring hospital to a mean of 498 mm Hg during the ex vivo evaluation. After 1 hour of EVLP, PVR varied from 440-1454 dynes/sec/cm(5); LC was in the range of 26-90 mL/cmH(2)O. There was no histological deterioration after 10 hours of cold ischemia and 1 hour of EVLP. Conclusions. The ex vivo evaluation model can improve oxygenation capacity of ""marginal"" lungs rejected for transplantation. It has great potential to increase lung donor availability and, possibly, reduce time on the waiting list.

Impact of Cytomegalovirus Infection in Lung Transplant Patients Under Universal Prophylaxis: Single-Center Experience in Brazil

Introduction. Cytomegalovirus (CMV) infection, a common complication in lung transplant (LT) patients, is associated with worse outcomes. Therefore, prophylaxis and surveillance with preemptive treatment is recommended. Objectives. Describe the epidemiology and impact on mortality of CMV infection in LT patients receiving CMV prophylaxis. Methods. Single-center retrospective cohort of LT recipients from August 2003 to March 2008. We excluded patients with survival or follow-up shorter than 30 days. We reviewed medical charts and all CMV pp65 antigen results. Results. Forty-seven patients met the inclusion criteria and 19 (40%) developed a CMV event: eight CMV infections, seven CMV syndromes, and 15 CMV diseases. The mean number of CMV events for each patient was 1.68 +/- 0.88. Twelve patients developed CMV events during prophylaxis (5/12 had CMV serology D+/R-). Forty-six of the 47 patients had at least one episode of acute rejection (mean 2.23 +/- 1.1). Median follow-up was 22 months (range = 3-50). There were seven deaths. Upon univariate analysis, CMV events were related to greater mortality (P = .04), especially if the patient experienced more than two events (P = .013) and if the first event occurred during the first 3 months after LT (P = .003). Nevertheless, a marginally significant relationship between CMV event during the first 3 months after LT and mortality was observed in the multivariate analysis (hazards ratio: 7.46; 95% confidence interval: 0.98-56.63; P = .052). Patients with CMV events more than 3 months post-LT showed the same survival as those who remained CMV-free. Conclusion. Prophylaxis and preemptive treatment are safe and effective; however, the patients who develop CMV events during prophylaxis experience a worse prognosis.

Validation of a Cutoff Value on Echo Doppler Analysis to Replace Right Heart Catheterization During Pulmonary Hypertension Evaluation in Heart Transplant Candidates

Background. Heart transplantation (OHT) has traditionally been contraindicated in the presence of severe pulmonary hypertension (PH), as detected by right heart catheterization. Noninvasive methods are still not reliably accurate to make this evaluation. Objectives. Determine the efficacy of echo Doppler analysis for the diagnosis of severe PH. Methods. One hundred thirty patients (mean age = 42 +/- 15 years, 82 men) showed severe left ventricular dysfunction (mean ejection fraction = 29 +/- 12%; functional class III-IV). We excluded patients with atrial fibrillation, heart failure secondary to congenital disease, and valvulopathy. The pulmonary parameters defined as severe PH were: systolic pulmonary artery pressure (sPAP) >= 60 mm Hg; a mean transpulmonary gradient >= 15; or pulmonary vascular resistance >= 5 Wood units. Patients underwent a right heart catheterization using a Swan-Ganz catheter to measure hemodynamic parameters and to noninvasively estimate right-sided pressures from spectral Doppler recordings of tricuspid regurgitation velocity (right ventricular systolic pressure [RVsP]). A Pearson correlation of sPAP was obtained with RVsP by; the sensitivity of RVsP for the diagnosis of PH was determined by a receiver operating characteristic (ROC) curve. Results. A good correlation between sPAP and RVsP was obtained by Pearson correlation analysis (r = 0.64; 95% confidence interval [CI] 0.50-0.75; P < .001). The ROC curve analysis showed a sensitivity of 100%, a specificity of 37.2%, (95% CI 0.69-0.83, P < .0001) of a RVsP < 45 mm Hg (cutoff) on the exclusion of severe PH. Conclusions. The cutoff of RVsP < 45 mm Hg, on noninvasive echo Doppler evaluation of PH is an efficient method to replace invasive heart catheterization in OHT candidates.

Dobutamine Stress Echocardiography in Heart Transplant Recipients` Evaluation: The Role of Reinnervation

Introduction. Orthotopic heart transplantation renders the recipient denervated. This remodeling of the intrinsic cardiac nervous system should be taken in account during functional evaluation for allograft coronary artery disease. Dobutamine stress echocardiography (DSE) has been used to detect patients at greater risk. The aim of this study was to determine whether patients with various autonomic response levels, and supposed reinnervation patterns, show the same response to DSE. Methods. We studied 20 patients who had survived more than 5 years after orthotopic heart transplantation. All patients underwent a Holter evaluation. We considered patients with low variability to be those with less than a 40-bpm variation from the lowest to highest heart rate, so-called ""noninnenervated"" (group NI). Patients who had 40-bpm or more variation were considered to show high variability and called ""reinnervated"" (group RI). After that, all patients performed an ergometric test and DSE. Results. Groups were defined as NI (n = 9) and RI (n = 11). Ergometric tests confirmed this response with NI patients showing less variability when compared to RI patients (P = .0401). During DSE, patients showed similar median heart rate responses according to the dobutamine dose. Spearmen correlation showed r = 1.0 (P = .016). Conclusions: DES was effective to reach higher heart rates, probably related to catecholamine infusion. These findings may justify a better response when evaluating cardiac allograft vasculopathy in heart transplant patients.

Biopsy-Proven Pulmonary Determinants of Heart Disease

Heart disease (HD) can stress the alveolar blood-gas barrier, resulting in parenchymal inflammation and remodeling. Patients with HD may therefore display any of the symptoms commonly attributed to primary pulmonary disease, although tissue documentation of corresponding changes through surgical lung biopsy (SLB) is rarely done. Intent on exploring the basis of HD-related alveolar-capillary barrier dysfunction, a retrospective analysis of SLB histopathology was conducted in patients with clinically diagnosed HD, diffuse pulmonary infiltrates, and no evidence of primary pulmonary disease. Patients eligible for the study had a clinical diagnosis of heart disease, acute or chronic, and presented with diffuse infiltrates on chest X-ray. All qualified subjects (N = 23) who underwent diagnostic SLB between January 1982 and December 2005 were subsequently examined. Specific biopsy parameters investigated included demonstrable edema, siderophage influx, hemorrhage, venous and lymphatic ectasia, vascular sclerosis, capillary congestion, and fibroblast proliferation. Based on observed alveolar-capillary barrier (ACB) alterations, three main morphologic groups emerged: one group (6 patients) with alveolar edema; a second group (11 patients) characterized by pulmonary congestion; and a final group (6 patients) showing microscopic foci of acute ACB lung injury. Alveolar-capillary stress due to acute high-pressure or volume overload often manifests as diffuse pulmonary infiltrates with variable but generally predictable histopathology. In patients with biopsy-proven alveolar edema, pulmonary congestion, or acute microscopic lung injury, the clinician must be alert for the possibility of primary heart disease, particularly if the patient is elderly or when a history of myocardial, valvular, or coronary vascular disease exists.

Influence of Single-Nucleotide Polymorphisms on C-Reactive Protein Levels in Chronic Kidney Disease Before and After Kidney Transplantation

Introduction. We sought to evaluate 2 sing] e-nucleotide polymorphisms (SNPs) in the C-reactive protein (CRP) gene promoter region for their effects on CRP levels in chronic kidney disease (CKD) patients before and after a successful kidney transplantation. Methods. Fifty CKD patients were evaluated before and at the first and second years after the graft. Two SNPs were studied, a bi-allelic (G -> A) at the -409 and a tri-allelic (C -> T -> A) variation at the -390 position in the CRP gene. Results. All patients presented the -409GG genotype. At the -390 position, the ""A"" allele was not found; there were 15 ""CC"" patients, 11 ""TT"" patients, and 24 ""CT"" patients. CRP levels were different among patients with various genotypes (P < .019). Also the presence of the allele ""T"" was sufficient to determine differences in CRP levels both in pretransplantation (P = .045) and at 1 year posttransplantation (P = .011), but not at the second year (P = .448). Conclusion. SNPs at the -390 position of the CRP gene promoter region influence CRP basal levels in such a way that the ""C"" allele correlated with the lowest and the ""T"" with the highest. We did not observe this influence in our patients at the second year posttransplantation.

Acute chagasic myocardiopathy after orthotopic liver transplantation with donor and recipient serologically negative for Trypanosoma cruzi: A case report

Chagas disease (American trypanosomiasis) is caused by the protozoan parasite Trypanosoma cruzi. Chagas disease following solid-organ transplantation has occurred in Latin America. This report presents the occurrence of Chagas disease despite negative serological tests in both the donor and the recipient, as well as the effectiveness of treatment. A 21-year-old woman from the state of Sao Paulo (Brazil) underwent cadaveric donor liver transplantation in November 2005, due to cirrhosis of autoimmune etiology. Ten months after liver transplantation, she developed signs and symptoms of congestive heart failure (New York Heart Association functional class IV). The echocardiogram, which was normal preoperatively, showed dilated cardiac chambers, depressed left ventricular systolic function (ejection fraction = 35%) and moderate pulmonary hypertension. Clinical investigation discarded ischemic heart disease and autoimmune and other causes for heart failure. Immuno fluorescence (immunoglobulin M and immunoglobulin G) and hemagglutination tests for T cruzi were positive, and abundant T cruzi amastigotes were readily identified in myocardial biopsy specimens. Treatment with benznidazole for 2 months yielded an excellent clinical response. At the moment of submission, the patient remains in functional class I. This case highlighted that more appropriate screening for T cruzi infection is mandatory in potential donors and recipients of solid-organ transplants in regions where Chagas disease is prevalent. Moreover, it stressed that this diagnosis should always be considered in recipients who develop cardiac complications, since negative serological tests do not completely discard the possibility of disease transmission and since good results can be achieved with prompt trypanocidal therapy.

Cytomegalovirus and other herpesviruses infections in heart and bone marrow transplant recipients

From January 1988 to January 1989 all the heart transplant and bone marrow recipients at the Instituto do Coração of the Hospital das Clínicas of the University of São Paulo Medical School were studied for the incidence and morbidity associated with herpesviruses infections after transplantation. Five bone marrow and 5 heart transplant recipients were followed for a mean of 4.2 months post-transplantation. All the patients were seropositive for cytomegalovirus (CMV) before admission and 80% experienced one or more recurrences during the observation period. Of the 12 episodes of CMV infection, that were identified in this study, 83% were accompanied by clinical or laboratory abnormalities. However, there was only one case of severe disease. The overall incidence of infection for herpes simplex (HSV) was 50%. Although most of HSV reactivations were oral or genital, one case of HSV hepatitis occurred. One of the 6 episodes of HSV infections that were treated with acyclovir showed an unsatisfactory response and was successfully managed with ganciclovir. All the individuals had anti-varicella zoster virus antibodies, but none of them developed infection. The study emphasizes the importance of active diagnostic surveillance of herpesvirus infections in transplant patients. Both CMV and HSV reactivations showed high incidence and important morbidity and thus, deserve prophylactic therapy.

Prognostic Value of a New Cardiopulmonary Exercise Testing Parameter in Chronic Heart Failure: Oxygen Uptake Efficiency at Peak Exercise - Comparison with Oxygen Uptake Efficiency Slope

INTRODUCTION: A growing body of evidence shows the prognostic value of oxygen uptake efficiency slope (OUES), a cardiopulmonary exercise test (CPET) parameter derived from the logarithmic relationship between O(2) consumption (VO(2)) and minute ventilation (VE) in patients with chronic heart failure (CHF). OBJECTIVE: To evaluate the prognostic value of a new CPET parameter - peak oxygen uptake efficiency (POUE) - and to compare it with OUES in patients with CHF. METHODS: We prospectively studied 206 consecutive patients with stable CHF due to dilated cardiomyopathy - 153 male, aged 53.3±13.0 years, 35.4% of ischemic etiology, left ventricular ejection fraction 27.7±8.0%, 81.1% in sinus rhythm, 97.1% receiving ACE-Is or ARBs, 78.2% beta-blockers and 60.2% spironolactone - who performed a first maximal symptom-limited treadmill CPET, using the modified Bruce protocol. In 33% of patients an cardioverter-defibrillator (ICD) or cardiac resynchronization therapy device (CRT-D) was implanted during follow-up. Peak VO(2), percentage of predicted peak VO(2), VE/VCO(2) slope, OUES and POUE were analyzed. OUES was calculated using the formula VO(2) (l/min) = OUES (log(10)VE) + b. POUE was calculated as pVO(2) (l/min) / log(10)peakVE (l/min). Correlation coefficients between the studied parameters were obtained. The prognosis of each variable adjusted for age was evaluated through Cox proportional hazard models and R2 percent (R2%) and V index (V6) were used as measures of the predictive accuracy of events of each of these variables. Receiver operating characteristic (ROC) curves from logistic regression models were used to determine the cut-offs for OUES and POUE. RESULTS: pVO(2): 20.5±5.9; percentage of predicted peak VO(2): 68.6±18.2; VE/VCO(2) slope: 30.6±8.3; OUES: 1.85±0.61; POUE: 0.88±0.27. During a mean follow-up of 33.1±14.8 months, 45 (21.8%) patients died, 10 (4.9%) underwent urgent heart transplantation and in three patients (1.5%) a left ventricular assist device was implanted. All variables proved to be independent predictors of this combined event; however, VE/VCO2 slope was most strongly associated with events (HR 11.14). In this population, POUE was associated with a higher risk of events than OUES (HR 9.61 vs. 7.01), and was also a better predictor of events (R2: 28.91 vs. 22.37). CONCLUSION: POUE was more strongly associated with death, urgent heart transplantation and implantation of a left ventricular assist device and proved to be a better predictor of events than OUES. These results suggest that this new parameter can increase the prognostic value of CPET in patients with CHF.

Heart hypoplasia in an animal model of congenital diaphragmatic hernia

PURPOSE: In previous papers, we described a new experimental model of congenital diaphragmatic hernia in rabbits, and we also reported noninvasive therapeutic strategies for prevention of the functional and structural immaturity of the lungs associated with this defect. In addition to lung hypoplasia, pulmonary hypertension, biochemical, and structural immaturity of the lungs, the hemodynamics of infants and animals with congenital diaphragmatic hernia are markedly altered. Hence, cardiac hypoplasia has been implicated as a possible cause of death in patients with congenital diaphragmatic hernia, and it is hypothesized to be a probable consequence of fetal mediastinal compression by the herniated viscera. Cardiac hypoplasia has also been reported in lamb and rat models of congenital diaphragmatic hernia. The purpose of the present experiment was to verify the occurrence of heart hypoplasia in our new model of surgically produced congenital diaphragmatic hernia in fetal rabbits. METHODS: Twelve pregnant New Zealand rabbits underwent surgery on gestational day 24 or 25 (normal full gestational time - 31 to 32 days) to create left-sided diaphragmatic hernias in 1 or 2 fetuses per each doe. On gestational day 30, all does again underwent surgery, and the delivered fetuses were weighed and divided into 2 groups: control (non-surgically treated fetuses) (n = 12) and congenital diaphragmatic hernia (n = 9). The hearts were collected, weighed, and submitted for histologic and histomorphometric studies. RESULTS: During necropsy, it was noted that in all congenital diaphragmatic hernia fetuses, the left lobe of the liver herniated throughout the surgically created defect and occupied the left side of the thorax, with the deviation of the heart to the right side, compressing the left lung; consequently, this lung was smaller than the right one. The body weights of the animals were not altered by congenital diaphragmatic hernia, but heart weights were decreased in comparison to control fetuses. The histomorphometric analysis demonstrated that congenital diaphragmatic hernia promoted a significant decrease in the ventricular wall thickness and an increase in the interventricular septum thickness. CONCLUSION: Heart hypoplasia occurs in a rabbit experimental model of congenital diaphragmatic hernia. This model may be utilized for investigations in therapeutic strategies that aim towards the prevention or the treatment of heart hypoplasia caused by congenital diaphragmatic hernia.

Growth hormone for optimization of refractory heart failure treatment

It has been reported that growth hormone may benefit selected patients with congestive heart failure. A 63-year-old man with refractory congestive heart failure waiting for heart transplantation, depending on intravenous drugs (dobutamine) and presenting with progressive worsening of the clinical status and cachexia, despite standard treatment, received growth hormone replacement (8 units per day) for optimization of congestive heart failure management. Increase in both serum growth hormone levels (from 0.3 to 0.8 mg/l) and serum IGF-1 levels (from 130 to 300ng/ml) was noted, in association with clinical status improvement, better optimization of heart failure treatment and discontinuation of dobutamine infusion. Left ventricular ejection fraction (by MUGA) increased from 13 % to 18 % and to 28 % later, in association with reduction of pulmonary pressures and increase in exercise capacity (rise in peak VO2 to 13.4 and to 16.2ml/kg/min later). The patient was "de-listed" for heart transplantation. Growth hormone may benefit selected patients with refractory heart failure.

Heart transplant in a patient with complete absence of the pericardium

We report the case of a heart transplant in which the recipient patient had a total congenital absence of the pericardium. Associated with this, we found a major disproportion between the size of the recipient's mediastinal cavity and the size of the donor's heart. To prevent twisting of the great arteries, we placed the graft on the left diaphragm muscle and beneath the left lung, which resulted in an uneventful early and late postoperative course.