E.A. Bocchi

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.

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.

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) >or= 60 mm Hg; a mean transpulmonary gradient >or= 15; or pulmonary vascular resistance >or= 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.

Prognostic value of coronary and microvascular flow reserve in patients with nonischemic dilated cardiomyopathy.

BACKGROUND Coronary and microvascular blood flow reserve have been established as important predictors of prognosis in patients with cardiovascular disease. The aim of this study was to assess the value of coronary flow velocity reserve (CFVR) and real-time myocardial perfusion echocardiography (RTMPE) for predicting events in patients with nonischemic dilated cardiomyopathy. METHODS One hundred ninety-five patients (mean age 54 ± 12 years; 66% men) with dilated cardiomyopathy (left ventricular ejection fraction < 35% and no obstructive coronary disease on invasive angiography or multidetector computed tomography) who underwent dipyridamole stress (0.84 mg/kg over 10 min) RTMPE were prospectively studied. CFVR was calculated as the ratio of hyperemic to baseline peak diastolic velocities in the distal left anterior coronary artery. The replenishment velocity (β), plateau of acoustic intensity (A(N)), and myocardial blood flow reserve were obtained from RTMPE. RESULTS Mean CFVR was 2.07 ± 0.52, mean A(N) reserve was 1.05 ± 0.09, mean β reserve was 2.05 ± 0.39, and mean myocardial blood flow reserve (A(N) × β) was 2.15 ± 0.48. During a median follow-up period of 29 months, 45 patients had events (43 deaths and two urgent transplantations). Independent predictors of events were left atrial diameter (relative risk, 1.16; 95% confidence interval, 1.08-1.26; P < .001) and β reserve ≤ 2.0 (relative risk, 3.22; 95% confidence interval, 1.18-8.79; P < .001). After adjustment for β reserve, CFVR and myocardial blood flow reserve no longer had predictive value. Left atrial diameter added prognostic value over clinical factors and left ventricular ejection fraction (χ2 = 36.8-58.5, P < .001). Beta reserve added additional power to the model (χ2 = 70.2, P < .001). CONCLUSIONS Increased left atrial diameter and depressed β reserve were independent predictors of cardiac death and transplantation in patients with nonischemic dilated cardiomyopathy. Beta reserve by RTMPE provided incremental predictive value beyond that provided by current known prognostic clinical and echocardiographic factors.

Immunohistochemical Quantification of Inflammatory Cells in Endomyocardial Biopsy Fragments After Heart Transplantation: A New Potential Method to Improve the Diagnosis of Rejection After Heart Transplantation

Inconsistencies in cardiac rejection grading systems corroborate the concept that the evaluation of inflammatory intensity and myocyte damage seems to be subjective. We studied in 36 patients the potential role of the immunohistochemical (IHC) counting of inflammatory cells in endomyocardial biopsy (EMB) as an objective tool, testing the hypothesis of correlation between the International Society for Heart and Lung Transplantation 2004 rejection and IHC counting of inflammatory cells. We observed a progressive increment in CD68+ cells/mm(2) (P = .000) and CD3+ cells/mm(2) (P = .000) with higher rejection grade. A strong correlation between the grade of cellular rejection and both CD68+ cells/mm(2) and CD3+ cells/mm(2) was obtained (P = .000). One patient with CD3+ and CD68+ cells/mm(2) above the upper limit of the 95% confidence interval for cells/mm(2) found in rejection grade 1R evolved to rejection grade 2R without treatment. In patients with 2R that did not respond to treatment the values of CD68+ or CD3+ cells were higher than the overall median values for rejection grade 2R. For diagnosis of rejection needing treatment, the CD68+ and CD3+ cells/mm(2) areas under the receiver operating characteristic curves were 0.956 and 0.934, respectively. IHC counting of mononuclear inflammatory infiltrate in EMB seems to have additive potential role in evaluation of EMB for the diagnosis and prognosis of rejection episodes.

Evolução a longo prazo e complicaçöes da hipertensão arterial após transplante cardíaco

PURPOSE: To evaluate the progression of arterial hypertension (AH) and its consequences , in patients submitted to cardiac transplantation (CT) in use of cyclosporine (CY). METHODS: In 65 patients submitted to orthotopic CT, we evaluated blood pressure, serum creatinine and blood levels of CY before, 15 and 30 days, and 6, 12, 24, 48 and 60 months after CT; in 20 patients we analyzed cardiac index and systemic vascular resistance pre-CT, 15 and 30 days, 6 and 12 months after CT; in 33 patients, we studied anatomic and functional modifications by echocardiography, 24±13 months after CT. RESULTS: Thirty days after CT, AH was present in 58.5% (50% mild), and after one year, 93% of patients were hypertensives (85% moderate-to-severe), remaining unchanged during the rest of follow-up. The serum creatinine progressively increased, reaching values significantly higher than those pre-CT after one year, persisting with a mild increment until 60 months. Echocardiography showed left ventricle hypertrophy in 54% of patients, all of which had normal function. Two patients died as a direct consequence of hypertensive complications. CONCLUSION: AH in patients submitted to CT on CY use occurs early, increases in prevalence and severity during the follow-up and is mediated by an increase in vascular resistance. Also, the AH does not correlate to CY blood levels or nefrotoxicity, but it can impair renal function and compromise longevity of transplantation by inducing ventricular hypertrophy.PURPOSE To evaluate the progression of arterial hypertension (AH) and its consequences, in patients submitted to cardiac transplantation (CT) in use of cyclosporine (CY). METHODS In 65 patients submitted to orthotopic CT, we evaluated blood pressure, serum creatinine and blood levels of CY before, 15 and 30 days, and 6, 12, 24, 48 and 60 months after CT; in 20 patients we analyzed cardiac index and systemic vascular resistance pre-CT, 15 and 30 days, 6 and 12 months after CT; in 33 patients, we studied anatomic and functional modifications by echocardiography, 24 +/- 13 months after CT. RESULTS Thirty days after CT, AH was present in 58.5% (50% mild), and after one year, 93% of patients were hypertensives (85% moderate-to-severe), remaining unchanged during the rest of follow-up. The serum creatinine progressively increased, reaching values significantly higher than those pre-CT after one year, persisting with a mild increment until 60 months. Echocardiography showed left ventricle hypertrophy in 54% of patients, all of which had normal function. Two patients died as a direct consequence of hypertensive complications. CONCLUSION AH in patients submitted to CT on CY use occurs early, increases in prevalence and severity during the follow-up and is mediated by an increase in vascular resistance. Also, the AH does not correlate to CY blood levels or nefrotoxicity, but it can impair renal function and compromise longevity of transplantation by inducing ventricular hypertrophy.

Incidência de coronariopatia após o transplante cardíaco ortotópico

O presente estudo tem por finalidade analisar tardiamente o padrao anatomico evolutivo das arterias coronarias do coracao transplantado. Para cumprir tal proposicao foram selecionados 22 pacientes submetidos ao transplante cardiaco ortotopico, com seguimento pos-operatorio superior a 36 meses. As variaveis eleitas para este fim foram aferidas anualmente ate o quinto ano de pos-operatorio. A analise da ventriculografia mostrou a estabilidade da fracao de ejecao (p=0,99) em valores normais. A cineangiocoronariografia sequencial evidenciou incidencia crescente de lesoes arteriais com comprometimento da funcao contratil. As lesoes obstrutivas acometeram as arterias coronarias difusamente, com predominio no territorio distai. Os episodios de rejeicao aguda e a etiologia da cardiomiopatia nao modificaram a evolucao natural da aterosclerose coronaria.

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.

291 A cutoff point for peak VO2 with beta‐blocker therapy in heart failure patients

Introduction: An attenuated heart rate recovery (HRR) following exercise test (ET) portends a higher mortality risk in asymptomatic subjects as in patients (pts) with coronary heart disease. Its prognostic value in heart failure pts has yet to be confirmed. The aim of this study was to determine the prognostic implications of attenuated HRR relative to well established prognostic factors peak oxygen uptake (pVO2) and VE/VCO2 slope in heart failure. Methods: We evaluated 171 pts (age 55±10 years, 45 female) with an ejection fraction <40% who underwent a treadmill-based cardiopulmonary exercise test (CPET) for risk stratification. The difference between maximal heart frequency and the frequency at the end of the first minute of recovery was defined as HRR. ROC curve analyses were used to identify the HRR value that more accurately predicted death. Results: Therapy at the time of CPET included a beta-blocker in 149 pts (77%) and an ACE inhibitor or ARB in 177 pts (91%). During follow-up (920±449 days) 12 pts died. HRRwas significantly lower in pts who died (7.7±6.0 bpm vs 15.8±13.7 bpm; P= 0.042). HRR ≤10 bpm (present in 70 pts) was associated with higher mortality, even after adjustment for the effects of age, gender, body mass index, coronary heart disease aetiology, diabetes, smoking, left bundle branch block, mean blood pressure, heart rate, pVO2, and VE/VCO2 slope (adjusted HR= 5.2, 95% CI, 1.0-26.1). In this multivariable analysis, VE/CO2 slope remained an independent prognostic factor (HR=1.04 per unit increase, 95% CI, 1.0-1.1), but not pVO2. Conclusions: In pts with left ventricular systolic dysfunction, a HRR ≤10 bpm at the first minute after a cardiopulmonary exercise test is an independent predictor of mortality, and adds prognostic information to the VE/VCO2 slope. HRR should be considered when estimating the outcome of heart failure pts with low ejection fraction.

Evolução tardia do transplante cardíaco na doença de Chagas: long-term evolution in cardiac transplantation

Nas formas cardiacas da doenca de Chagas que evoluem com insuficiencia cardiaca refrataria ao tratamento clinico, o transplante e a unica alternativa, ao lado da cardiomioplastia. Os autores apresentam a evolucao tardia de seis pacientes com miocardiopatia chagasica terminal submetidos a transplante cardiaco ortotopico. O periodo medio de observacao foi de 25,2 meses. O diagnostico de reativacao da doenca de Chagas apoiou-se na observacao clinica, na investigacao laboratorial do parasita, nas biopsias endomiocardicas e dos nodulos de subcutâneo. A analise dos resultados demonstra que: 1) os testes laboratoriais mostraram-se ineficazes no diagnostico da reativacao da doenca, sendo que as biopsias mostraram maior indice de positividade; 2) a pulsoterapia com corticoide predispoe a reativacao; 3) a doenca linfoproliferativa apresenta alta incidencia na doenca de Chagas, sendo a principal complicacao tardia. Possivelmente, o benzonidazol apresente seu efeito oncogenico potencializado. Tendo em vista o carater endemico da doenca e a falta de alternativa terapeutica, tornou-se obrigatoria a analise do esquema imunossupressor, do tratamento da reativacao e a maior experiencia clinica, para posicoes mais definidas.