Behavior profile of family members of donors and nondonors of organs.

UNLABELLED: Organ transplant shortage is a global problem caused by several factors, most of which are related to members of the family, who play a major role in the donation process. OBJECTIVE: We sought to determine the most determinant features in the donor profile that relate to positive decisions versus refusal of donation. MATERIAL AND METHODS: Fifty-six families who were approached by the Organ Procurement Organization (OPO) from November 2004 to April 2006 agreed to participate in this work. To assess donor profiles, we used a structured interview. RESULTS: Parental involvement directly in decisions about donation lead to significantly less frequent consent (P = .005), young donor age was associated with a reduced probability of donation (P = .002), violent death negatively influenced donation consent, excluding suicide (P = .004). CONCLUSION: The present study showed violent death, young patient age, and parental donation consent to be the most important factors that make it harder to obtain consent organ donation. When a collateral relative (sibling/uncle) or children were responsible for the donation decision, there was more success of consent.

Heart transplantation in arrhythmogenic right ventricular dysplasia: case reports.

OBJECTIVE: Arrhythmogenic right ventricular dysplasia (ARVD) is a myocardial disease of familiar, origin where the myocardium is replaced by fibrofatty tissue predominantly in the right ventricle. Herein we have presented the clinical courses of 4 patients with ARVD who underwent orthotopic heart transplantation. PATIENTS AND METHODS: Among 358 adult patients undergoing heart transplantation, 4 (1.1%) displayed ARVD. The main indication for transplantation was the progression to heart failure associated with arrhythmias. All 4 patients displayed rapid, severe courses leading to heart failure with left ventricular involvement and uncontrolled arrhythmias. RESULTS: In all cases the transplantation was performed using a bicaval technique with prophylactic tricuspid valve annuloplasty. One patient developed hyperacute rejection and infection, leading to death on the 7th day after surgery. The other 3 cases showed a good evolution with clinical remission of the symptoms. Pathological study of the explanted hearts confirmed the presence of the disease. CONCLUSIONS: ARVD is a serious cardiomyopathy that can develop malignant arrhythmias, severe ventricular dysfunction with right ventricular predominance, and sudden cardiac death. Orthotopic heart transplantation must always be considered in advanced cases of ARVD with malignant arrhythmias or refractory congestive heart failure with or without uncontrolled arrhythmias, because it is the only way to remit the symptoms and the disease.

Massive degeneration and atrophy of the native heart after heterotopic transplantation: a case report.

Extreme myocardial degeneration leading to advanced stages of cardiomyopathy with extensive atrophy is rarely observed before patients die. However, heterotopic transplantation is a special situation wherein this phenomenon can be observed. The greater part of the failed heart shows recuperation after receiving circulatory assistance by reduction of myocardial work. Herein we have reported an unusual behavior of degenerative cardiomyopathy associated with intense myocardial apoptosis resulting in extreme ventricular atrophy after heterotopic heart transplantation. An 11-year-old girl with end-stage heart failure due to dilated cardiomyopathy of undetermined etiology without pulmonary hypertension underwent heterotopic cardiac transplantation with an undersized (by weight mismatch) donor heart. After 9 years heart failure reappeared due to native heart enlargement leading to allograft compression. The patient underwent native heart replacement leaving her with 2 donor hearts. Despite normal hemodynamic recuperation, the patient experienced massive arterial microemboli which led to death. Pathological studies showed exuberant myocardial degeneration in the native heart with intense atrophy of the muscle and gigantic ventricular enlargement. The left ventricle wall was extremely thin with rarefaction of cardiomyocytes and replacement by fibrosis. The right ventricle showed old extensive thrombosis. In conclusion, this report is not usual as it is not frequent to observe cardiomyopathy with an intense degree of myocardial degeneration and atrophy, because the patient dies earlier. In special situations it is possible that a recipient may have 2 donor hearts with normal hemodynamics. Heterotopic heart transplantation is a surgical alternative in a priority situation offering excellent outcomes; however, the native heart must be removed when there is compromise of the function of the heterotopic allograft.

Endomyocardial biopsy as risk factor in the development of tricuspid insufficiency after heart transplantation.

OBJECTIVE: Endomyocardial biopsy (EMB), which is used to monitor for rejection, may cause tricuspid regurgitation (TR) after orthotopic heart transplantation (OHT). The purpose of this investigation was to examine the occurrence of tricuspid valve tissue in myocardial specimens obtained by routine EMB performed after OHT. PATIENTS AND METHODS: From January 2000 to July 2008, 125 of the patients who underwent OHT survived more than 1 month. Their follow-up varied from 1 month to 8.5 years (mean, 5.1 +/- 3.7 years). EMB was the gold standard examination and myocardial scintigraphy with gallium served as a screen to routinely monitor rejection. RESULTS: Each of 428 EMB including 4 to 7 fragments, totaling 1715 fragments, were reviewed for this study. The number of EMB per patient varied from 3 to 8 (mean, 4.6 +/- 3.5). Histopathological analysis of these fragments showed tricuspid tissue in 4 patients (3.2%), among whom only 1 showed aggravation of TR. CONCLUSIONS: EMB remains the standard method to diagnose rejection after OLT. It can be performed with low risk. Reducing the number of EMB using gallium myocardial scintigraphy or other alternative methods as well as adoption of special care during the biopsy can significantly minimize trauma to the tricuspid valve.

Autoimmunity in Chagas' disease. Identification of cardiac myosin-B13 Trypanosoma cruzi protein crossreactive T cell clones in heart lesions of a chronic Chagas' cardiomyopathy patient.

Heart tissue destruction in chronic Chagas' disease cardiomyopathy (CCC) may be caused by autoimmune recognition of heart tissue by a mononuclear cell infiltrate decades after Trypanosoma cruzi infection. Indirect evidence suggests there is molecular mimicry between T. cruzi and heart tissue. In murine models of CCC, antibodies and CD4+ T cells recognize myosin, the major heart protein. We recently identified a heart-specific epitope of cardiac myosin heavy chain (residues 1442-1447, AAALDK) that is crossreactive with a homologous sequence (AAAGDK) of the immunodominant T. cruzi antigen B13. Furthermore, cardiac myosin-B13 crossreactive antibodies are present in 100% CCC patients vs 14% asymptomatic T. cruzi-seropositive individuals (P = 2.3 x 10(-6)), suggesting a role for molecular mimicry between cardiac myosin and B13 in CCC pathogenesis. In this paper, we obtained heart-infiltrating T cell clones from CCC patients to assess whether molecular mimicry between cardiac myosin and B13 is directly involved in the genesis of heart lesions. We identified T cell clones derived from CCC heart lesions simultaneously responsive to cardiac myosin heavy chain (but not skeletal myosin heavy chain) and B13 T. cruzi protein, but could not find T cell clones primarily reactive to any T. cruzi antigen. Together with the association of myosin-B13 crossreactive antibodies with CCC, the present data strongly suggest the relevance of molecular mimicry between cardiac myosin and the T. cruzi protein B13 in the pathogenesis of heart lesions in chronic Chagas' disease cardiomyopathy.

Acute effects of a single dose of phosphodiesterase type 5 inhibitor (sildenafil) on systemic arterial blood pressure during exercise and 24-hour ambulatory blood pressure monitoring in heart transplant recipients.

BACKGROUND: Arterial systemic hypertension (SH) can be associated with a decrease in endothelium-dependent nitric oxide (NO). Sildenafil increases cyclic guanosine monophosphate (cGMP), a mediator of NO. However, little is known about the effects of PDE5 inhibition on 24-hour ambulatory pressure (ABP) and exercise blood pressure, noreprinephrine (Nor), and exercise capacity, especially after orthotopic heart transplantation (OHT). METHODS: We studied 22 OHT patients who on the 1st day underwent a cardiopulmonary (CP) self-controlled treadmill 6' walk test (6') and, then, an ECG monitored CP treadmill maximal exercise test (Ex) within 60 and 90 minutes after oral Sildenafil (Sil; 50 mg) or placebo (Pl) given at random, and ABP. We determined at basal position (b), in the last minute of the 6' and at the peak Ex, the HR (bpm), Systolic blood pressure (SBP), and diastolic blood pressure (DBP), (mm Hg), VO2 (mL/kg/min), Slope VE/VCO2, exercise time (ET, min), distance (D; miles), and Nor (pg/mL). Also, after CP tests, 24-h SBP and DBP, the measurements were repeated on the 2nd day when the cross-over was done. RESULTS: Sil significantly reduced blood pressure in the basal position and during exercise. It also promoted a significant reduction in SBP and DBP during 24 hours, daytime and nighttime. Sil did not change exercise capacity. CONCLUSION: The NO-cGMP pathway seems to play a role in blood pressure control in OHT. In addition to antihypertensive therapy, PDE5 inhibition may have potential beneficial effects on hypertensive OHT.

Prophylactic donor tricuspid annuloplasty in orthotopic bicaval heart transplantation.

OBJECTIVE: The objective of this study was to evaluate the effects of prophylactic heart donor tricuspid annuloplasty to improve the degree of valvar regurgitation and the hemodynamic performance after orthotopic heart transplantation using bicaval anastomosis. METHODS: From March 1985 to December 2005, of the 368 patients undergoing orthotopic heart transplantation, 20 patients were selected because they survived more than 6 months. They were divided into 2 groups: group I-10 patients underwent prophylactic heart donor tricuspid annuloplasty by the De Vega technique; group II-10 patients did not receive a graft with this procedure. Their presurgical clinical characteristics were the same. In the postsurgical period, tricuspid regurgitation degree evaluated by transthoracic Doppler echocardiography was qualified from 0 to 3: 0 = absent; 1 = mild; 2 = moderate; and 3 = severe. Myocardial performance was evaluated by the ventricular ejection fraction and by an invasive hemodynamic study, performed during routine endomyocardial biopsies. RESULTS: At a follow-up of 14.6 +/- 4.3 months (6 and 16 months), group I showed no mortality, whereas group II had 10% (P > .05). However, it was not related to the annuloplasty. The mean degree of tricuspid regurgitation in group I was 0.4 +/- 0.6; in group II, 1.6 +/- 0.8 (P < .05). There was a significant difference between the 2 groups in the right atrium pressure, which was higher in group II. CONCLUSIONS: Prophylactic tricuspid annuloplasty in the heart donor significantly reduced the degree of valvular regurgitation after heart transplantation using a bicaval anastomosis without significantly interfering with the hemodynamic performance of the allograft.

Methotrexate associated to lipid core nanoparticles improves cardiac allograft vasculopathy and the inflammatory profile in a rabbit heart graft model.

Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and has no effective treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and concentrates them in the heart graft. The aim of the study was to investigate the effects of methotrexate (MTX) associated to LDE. Rabbits fed a 0.5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg·kg-1·day-1 orally) and allocated to treatment with intravenous LDE-MTX (4 mg/kg, weekly, n=10) or with weekly intravenous saline solution (control group, n=10), beginning on the day of surgery. Animals were euthanized 6 weeks later. Compared to controls, grafts of LDE-MTX treated rabbits showed 20% reduction of coronary stenosis, with a four-fold increase in vessel lumen and 80% reduction of macrophage staining in grafts. Necrosis was attenuated by LDE-MTX. Native hearts of both LDE-MTX and Control groups were apparently normal. Gene expression of lipoprotein receptors was significantly greater in grafts compared to native hearts. In LDE-MTX group, gene expression of the pro-inflammatory factors tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-18, vascular cell adhesion molecule-1, and matrix metalloproteinase-12 was strongly diminished whereas expression of anti-inflammatory interleukin-10 increased. LDE-MTX promoted improvement of the cardiac allograft vasculopathy and diminished inflammation in heart grafts.

Proteomic inventory of myocardial proteins from patients with chronic Chagas' cardiomyopathy.

Chronic Chagas' disease cardiomyopathy (CCC) is an often fatal outcome of Trypanosoma cruzi infection, with a poorer prognosis than other cardiomyopathies. CCC is refractory to heart failure treatments, and is the major indication of heart transplantation in Latin America. A diffuse myocarditis, plus intense myocardial hypertrophy, damage and fibrosis, in the presence of very few T. cruzi forms, are the histopathological hallmarks of CCC. To gain a better understanding of the pathophysiology of CCC, we analyzed the protein profile in the affected CCC myocardium. Homogenates from left ventricular myocardial samples of end-stage CCC hearts explanted during heart transplantation were subjected to two-dimensional electrophoresis with Coomassie blue staining; protein identification was performed by MALDI-ToF mass spectrometry and peptide mass fingerprinting. The identification of selected proteins was confirmed by immunoblotting. We demonstrated that 246 proteins matched in gels from two CCC patients. They corresponded to 112 distinct proteins. Along with structural/contractile and metabolism proteins, we also identified proteins involved in apoptosis (caspase 8, caspase 2), immune system (T cell receptor ss chain, granzyme A, HLA class I) and stress processes (heat shock proteins, superoxide dismutases, and other oxidative stress proteins). Proteins involved in cell signaling and transcriptional factors were also identified. The identification of caspases and oxidative stress proteins suggests the occurrence of active apoptosis and significant oxidative stress in CCC myocardium. These results generated an inventory of myocardial proteins in CCC that should contribute to the generation of hypothesis-driven experiments designed on the basis of the classes of proteins identified here.

Later evolution after cardiac transplantation in Chagas' disease.

OBJECTIVE: This research reported the accumulated experience with cardiac transplantation in Chagas' disease, emphasizing reactivation, immunosuppression, and mortality. METHODS: Fifty-nine patients undergoing cardiac transplantation had Chagas' disease with classically accepted recipient selection criteria. In this series, 84.7% of the patients were functional class IV; 36.0% used vasopressor support; and 13.5% mechanical circulatory assistance. One patient received a heart and kidney transplantation. RESULTS: After the initial experience the doses of immunosuppressants were significantly reduced with improvement in outcomes. The diagnosis of the reactivation of disease was documented by the identification of parasite in the myocardium, or on subcutaneous or serological exams. Reactivation of disease was significantly reduced by decreasing the immunosuppression. Immediate mortality occurred in 10 cases: three infections, two allograft dysfunction, two rejections, and two sudden deaths. Subsequent mortality happened in 14 patients: four by lymphoma, three by infection, two by Kaposi's sarcoma two by rejection, two by constrictive pericarditis, and one by reactivation of disease in the brain. CONCLUSIONS: There's no correlation between the disease and pre- or postoperative prophylaxis. The early diagnosis and specific treatment of reactivation did not leave functional sequelae in the myocardium. Reduction in immunosuppression significantly reduced reactivation of disease and neoplasms. The combined transplantation can be realized safely with more care about the immunosuppressants.

Decrease in sulphated glycosaminoglycans in aortic dissection--possible role in the pathogenesis.

STUDY OBJECTIVE: The aim was to investigate alterations in sulphated glycosaminoglycans in aortic dissection. DESIGN: Aortic fragments were taken from 10 patients within the first 3 d after onset of symptoms of aortic dissection and from nine age matched patients with no aortic disease. Sulphated glycosaminoglycans were analysed and quantified by agarose gel electrophoresis and densitometry after degradation with specific enzymes. MEASUREMENTS AND MAIN RESULTS: The amount of chondroitin sulphate was similar (7.14 v 7.60 mg.g-1 of dry tissue, n = 10, p greater than 0.5) in patients with dissection and in the control group. Total sulphated glycosaminoglycan content was decreased (11.51 v 14.26 mg.g-1 of dry tissue, n = 10, p less than 0.001). This difference was due to heparan sulphate (1.79 v 2.48 mg.g-1 of dry tissue, n = 10, p less than 0.05) and mainly to dermatan sulphate (2.58 v 4.18 mg.g-1 of dry tissue, n = 10, p less than 0.001). The ratio of 6-/4-sulphated disaccharides after chondroitinase ABC digestion was increased in the affected group. No correlation between these biochemical results and a histological evaluation of mucoid content was found. On the other hand, a significant increase in chondroitin sulphate could be observed related to aging. CONCLUSIONS: The diminution in sulphated glycosaminoglycans and its possible relationship with fat, collagen, and other extracellular matrix molecules could lead to a weakness in the aortic wall related to the dissection.

Chylomicron metabolism in patients submitted to cardiac transplantation.

BACKGROUND: Development of coronary graft disease is the most important cause of late heart graft failure. Alterations in plasma lipid profile are frequent in heart transplant (HT) patients, but they seem not to be prominent. Currently, the metabolism of chylomicrons, the lipoproteins that carry dietary lipids absorbed by the intestine, was evaluated because chylomicron remnants are considered atherogenic. METHODS: An emulsion labeled with 3H-triolein and 14C-cholesteryl oleate and known to mimic the metabolic behavior of chylomicrons was injected intravenously after a 12-hr fast into 34 HT patients, 24 patients with end-stage heart failure (ESHF), and 30 healthy normolipidemic subjects. The plasma disappearance curves of the radioisotopes were determined from blood samples collected over 1 hr. In some of the patients and in controls, in vitro postheparin lipolytic activity was measured and an oral fat load test with postprandial measurement of triglyceridemia was performed. RESULTS: Fractional clearance rate (in m(-1), median [25%; 75%]) of both emulsion 3H-triolein and 14C-cholesteryl oleate was extremely diminished in HT patients (HT: 0.0114 [0.0114; 0.0179] and 0.2x10(-8) [0.2x10(-8); 0.0041, respectively]; ESHF: 0.0226 [0.0223; 0.0568] and 0.0160 [0.0055; 0.0189]; control subjects: 0.0270 [0.0226; 0.0392] and 0.0090 [0.0042; 0.0180], respectively, P<0.05). HT patients also had reduced postheparin lipolysis and marked elevation of postprandial triglyceridemia compared with the controls. CONCLUSIONS: HT patients develop accumulation in the plasma of chylomicrons and their remnants. The observed alterations were so intense that they may suggest an important involvement of atherogenic chylomicron remnants in coronary graft disease.

Comparison between antigenemia and a quantitative-competitive polymerase chain reaction for the diagnosis of cytomegalovirus infection after heart transplantation.

BACKGROUND: Antigenemia and quantitative polymerase chain reaction (PCR) are widely used for cytomegalovirus (CMV) diagnosis after heart transplantation due to their enhanced predictive values for disease detection when specific cut-off values are used. The purpose of this study was to compare, in the same patient setting, the predictive values of quantitative PCR and antigenemia for CMV disease detection, using specific cut-off values. METHODS: Thirty heart transplant receptors were ch prospectively monitored for active CMV infection and disease detection, using quantitative PCR and anti- po genemia. Positive and negative predictive values for pr CMV disease detection were calculated using cut-off pr values for both antigenemia (5 and 10 positive cells/300,000 neutrophils) and quantitative-PCR (50,000 and 100,000 copies/10(6) leukocytes). RESULTS: Active CMV infection was diagnosed in 93.3% of patients and CMV disease in 23.3%. The positive and negative predictive (%) values for CMV disease detection were 35/100 and 46.7/100, respectively, for quantitative PCR and antigenemia. Using 5 and 10 positive cells/300,000 neutrophils as cut-off values for antigenemia, the positive and negative predictive values (%) for disease detection were respectively 63.6/100 and 70/100. For quantitative PCR, the positive and th negative predictive values (%) for cut-off values of to 50,000 and 100,000 copies/10(6) leukocytes were 53.8/100 and 60/94.1, respectively. CONCLUSION: In our series, antigenemia and quantitative-PCR had enhanced and similar predictive values for CMV disease detection when specific cut-off values were used. The choice between these two methods for disease detection may rely less on their efficiency and more on the experience and familiarity with them.

Clinical and left ventricular function outcomes up to five years after dynamic cardiomyoplasty.

Improvement in congestive heart failure and left ventricular function after dynamic cardiomyoplasty has been reported in patients with severe cardiomyopathies, but the long-term effects of this procedure remain unclear. In this investigation 31 patients undergoing cardiomyoplasty for treatment of idiopathic dilated cardiomyopathy were annually investigated with radionuclide scintigraphy, Doppler echocardiography, and right-sided heart catheterization. They were in New York Heart Association functional class III or IV before the operation. No hospital deaths occurred, but one patient with progressive heart failure required urgent heart transplantation 42 days after cardiomyoplasty. The other patients were followed up from 6 to 70 months (mean 25.6 months) and 12 patients died at late follow-up. Actuarial survivals were 86% at 1 year, 61.4% at 2 years, and 42.5% at 3 to 5 years of follow-up. Multivariate analysis of factors influencing outcome showed that long-term survival was significantly affected by preoperative functional class and pulmonary vascular resistance. Functional class improved from 3.2 +/- 0.4 to 1.7 +/- 0.7 in the surviving patients (p < 0.01). Furthermore, left ventricular ejection fraction improved from 19.8% +/- 3% to 23.9% +/- 7.2% (p < 0.01), and significant changes in stroke index, arterial pressure, pulmonary wedge pressure, and left ventricular stroke work index were also found at 6 months of follow-up. In the late postoperative period, the left ventricular ejection fraction tended to decrease and returned to preoperative levels at 5 years, whereas hemodynamic variables did not change significantly. Thus, despite the tendency of the left ventricular ejection fraction to decrease at late follow-up, the long-term course of these patients seems to be characterized by the maintenance of hemodynamic improvement. However, long-term survival after cardiomyoplasty is limited by the severity of the patient's condition before the operation.

Left ventricular function changes after cardiomyoplasty in patients with dilated cardiomyopathy.

Dynamic cardiomyoplasty has been reported in the treatment of severe myocardial failure. In this investigation significant improvement of left ventricular function with dynamic cardiomyoplasty was demonstrated in patients with dilated cardiomyopathy or Chagas' disease for more than 1 year of follow-up. Thirteen patients with advanced heart failure who were in New York Heart Association class III or IV were operated on. There were no operative deaths. Patients were followed up for a mean of 11.5 months, and two patients died during the late follow-up period. Five of nine patients observed long term are in New York Heart Association class I, three in class II, and one in class III. At 3 months of follow-up, Doppler echocardiography demonstrated that left ventricular segmental wall shortening increased from 11.4% +/- 2.3% to 16.4% +/- 3.9% (p less than 0.01), and left ventricular stroke volume from 23.9 +/- 5.7 to 34.4 +/- 10 ml (p less than 0.01). Radioisotopic left ventricular ejection fraction improved from 20.9% +/- 3.3% to 25.4% +/- 7.7% (p = 0.06), and its better increases occurred in patients with lesser left ventricular end-diastolic dimensions. Cardiac catheterization showed that left ventricular stroke work index increased from 14.6 +/- 3.8 to 23.7 +/- 6.7 gm.m/m2 (p less than 0.01), whereas pulmonary wedge pressure decreased from 24.8 +/- 3.7 to 17.2 +/- 5.8 mm Hg (p less than 0.01). At 6 and 12 months of follow-up, all the preceding values remained essentially unchanged. Thus cardiomyoplasty improves left ventricular function and may halt the steady evolution of severe cardiomyopathies.

Partial left ventriculectomy with mitral valve preservation in the treatment of patients with dilated cardiomyopathy.

OBJECTIVE: This study reports initial results of partial left ventriculectomy performed with preservation of the mitral valve in the treatment of 27 patients with idiopathic dilated cardiomyopathy. METHODS: Patients were in New York Heart Association class III or IV. Partial ventriculectomy was performed as an isolated procedure in four patients and associated with mitral annuloplasty in 23 patients. There were four hospital deaths (14.8%) and the remaining patients were followed for 11.2 +/- 6 months. RESULTS: Decrease of left ventricular diastolic diameter (81.8 +/- 8.7 to 68.5 +/- 7.6 mm, p < 0.001) and improvement of left ventricular wall shortening (12% +/- 3.1% to 18.1% +/- 3.9%, p < 0.001) were demonstrated by echocardiography after the operation. Left ventricular radioisotopic angiography showed reduction of diastolic volume (495 +/- 124 ml to 352 +/- 108 ml, p < 0.001) and increase of ejection fraction (17.7% +/- 4.6% to 23.7% +/- 8.8%, p < 0.001). Right-sided heart catheterization demonstrated improvement of stroke index (24.3 +/- 7.7 ml/m2 to 28.3 +/- 7.6 ml/m2, p < 0.01) and decrease of pulmonary wedge pressure (23.2 +/- 8.8 mm Hg to 17 +/- 7 mm Hg, p < 0.01). Similar results were documented at 6 and 12 months of follow-up. Functional class improved from 3.6 +/- 0.5 to 1.4 +/- 0.6 (p < 0.001). However, seven patients died at midterm follow-up because of heart failure progression or arrhythmia-related events, and survival rate was 59.2% +/- 9.4% from 6 to 24 months of follow-up. CONCLUSIONS: Partial left ventriculectomy performed with preservation of the mitral valve improves left ventricular function and congestive heart failure in patients with dilated cardiomyopathy. Nevertheless, the high incidences of heart failure progression and arrhythmia-related deaths observed after this procedure preclude its wide clinical application.

Long-term outcome, survival analysis, and risk stratification of dynamic cardiomyoplasty.

METHODS: To analyze the long-term outcome of dynamic cardiomyoplasty, we retrospectively studied 127 consecutive patients who underwent this procedure in Paris, France (n = 76), São Paulo, Brazil (n = 37), and Portland, Oregon (n = 14). Preoperative data were collected for patients operated on between January 1985 and June 1994 and examined with respect to effect on long-term survival. Patients had a mean age of 50 +/- 13 years and were predominantly male (82%). In 46% the cause of disease was ischemic. Concomitant operations were performed in 22 patients. RESULTS: Operative mortality was 12% (15/127). Kaplan-Meier survival +/- standard error at 1 through 5 years was 73% +/- 4%, 57% +/- 5%, 49% +/- 6%, 44% +/- 6%, and 40% +/- 7%, respectively. There was a distinct improvement at 6 months in New York Heart Association functional class (3.2 +/- 0.05 vs 1.7 +/- 0.07, p < 0.0001) and a small but significant increase in left ventricular ejection fraction (20% +/- 0.8% vs 23% +/- 1.5%, p = 0.04). Ninety-day mortality was associated with low right ventricular ejection fraction, a blunted hemodynamic response to exercise testing, and requirement for an intraaortic balloon pump at the time of the operation. Using a stepwise Cox regression method of multivariable survival analysis (n = 101), we determined that atrial fibrillation, New York Heart Association class IV, high pulmonary capillary wedge pressure, and balloon pump use were independent variables simultaneously associated with poor overall survival. When metabolic testing variables were added to this model, peak oxygen consumption eliminated both pulmonary capillary wedge pressure and functional class from the model, albeit with fewer (n = 74) patients. CONCLUSION: Dynamic cardiomyoplasty is an evolving therapy for symptomatic congestive heart failure, the results of which may be enhanced by intelligent, risk-sensitive patient selection.

Low doses of inhaled nitric oxide in heart transplant recipients.

BACKGROUND: The purpose of this study was to assess the hemodynamic effects of low doses of inhaled nitric oxide in patients after orthotopic heart transplantation. METHODS: Two hours after the operation 10 adult patients who were still under anesthetic effects and undergoing mechanical ventilation inhaled, during 60 minutes, a mixture of nitrogen, oxygen, and nitric oxide (20 ppm). A standard profile of hemodynamic data was collected at baseline, at 30 minutes, at 30 more minutes of inhalation, and at the same points after nitric oxide suspension. RESULTS: A significant decrease was found from baseline to 60 minutes, immediately after nitric oxide inhalation in the following: systemic vascular resistance index 1268 +/- 409 to 1090 +/- 354 (p = 0.0161); pulmonary vascular resistance index 252 +/- 124 to 154 +/- 98 (p < 0.05); pulmonary vascular resistance index/systemic vascular resistance index ratio 0.21 +/- 0.09 to 0.14 +/- 0.08 (p = 0.0025); transpulmonary gradient 12 +/- 3 to 9 +/- 3 (p = 0.05). A significant increase was also found in cardiac index from 4.2 +/- 1.1 to 4.9 +/- 1.4 (p = 0.0007). Other parameters such as mean pulmonary, systemic, wedge and right atrial pressures, in addition to intrapulmonary shunting, heart rate, and oxygen extraction ratio, did not present any significant changes. The procedure was well tolerated by all patients, and no undesirable effects such as methemoglobin elevation or worsening of pulmonary hypertension after nitric oxide suspension were observed. CONCLUSIONS: The beneficial effects observed by inhaled nitric oxide in the pulmonary vascular resistance index/systemic vascular resistance index ratio, transpulmonary gradient, and cardiac index suggest that nitric oxide acts mainly in pulmonary territory and could be a possible pulmonary vasodilator agent used to control central hemodynamics after heart transplantation.

Usefulness of T-cell phenotype characterization in endomyocardial biopsy fragments from human cardiac allografts.

The mean numbers of cytotoxic/suppressor (CD8+) and helper/inducer (CD4+) T cells were determined in 111 successive endomyocardial biopsy fragments from eight cardiac allograft patients in an attempt to define their significance in the rejection process. Endomyocardial fragments from autopsy or donor hearts without myocarditis were evaluated as controls. The mean numbers of CD8+ and CD4+ T cells in the control group were 0.8 and 0.5 cells/field at x400 magnification, respectively. The mean numbers of CD8+ T cells per field in the cardiac allograft biopsies were 2.4, no rejection group; 5.4 mild rejection group; 11.1, moderate rejection group; and 4.9, resolving rejection group. The mean numbers of CD4+ T cells per field for the same groups were slightly lower than those of the CD8+ T cells. The number of CD8+ T cells per field reliably indicated the severity of rejection. Patients with normal numbers of CD8+ T cells and no evidence of rejection had better long-term outcomes (two or fewer moderate rejection episodes) than those with higher numbers. Analysis of the data suggests that the presence of two or fewer CD8+ T cells/field may be considered normal in the myocardial interstitium. The diagnosis of no evidence of rejection should be coupled to the presence of a normal number of CD8+ T cells. High numbers (greater than 10) of CD8+ T cells, even in absence of myocytolysis, should be treated more assertively, including the use of high doses of prednisone, because all our cases with high numbers showed a worse histologic picture at the subsequent biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Higher incidence of malignant neoplasms after heart transplantation for treatment of chronic Chagas' heart disease.

BACKGROUND: Heart transplantation is a new therapeutic procedure to treat heart failure resulting from Chagas' disease. Experimental studies have demonstrated neoplastic effects of benznidazole, which is used for treatment of Trypanosoma cruzi infection. We compared the incidence and characteristics of neoplasia after heart transplantation for treatment of chronic Chagas' disease with those of other diseases. METHODS: Sixteen patients with Chagas' disease and 75 patients with other diseases underwent heart transplantation. Benznidazole was administered to 14 patients with Chagas's disease either for prophylaxis (4 patients) or for treatment of Chagas' disease reactivation (10 patients). RESULTS: The survival rate of patients in the nonchagasic group was 90% at 1 year and 82.4% at 2 years, and the survival rate in the chagasic group was 63% at 1 year and 57% at 2 years. Six of 16 patients (37.5%) with Chagas' disease had malignant tumors after a mean follow-up time of 25.3+/-2.1 months in contrast to 2 of 75 patients (2.7%) in the nonchagasic group after 34.6+/-3.6 months of follow-up. In the chagasic group, lymphoproliferative disorder was diagnosed in three patients, Kaposi's sarcoma in two, and squamous cell carcinoma in one patient. Reactivation of T. cruzi infection was diagnosed in all patients who had lymphoproliferative disorder. One patient without Chagas' disease had lymphoproliferative disorder in the lung, and another had malignant schwannoma affecting the skin. CONCLUSIONS: We found a higher incidence of malignant neoplasia after heart transplantation for treatment of chronic Chagas' disease. It is likely that the neoplasia is the result of chronic infection with an immunomodulator protozoan, immunosuppression, reactivation of the T. cruzi infection, or the toxicity of therapeutic intervention with benznidazole.