NOEDIR ANTONIO GROPPO STOLF
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Cardio-Pneumologia, Faculdade de Medicina - Docente
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
LIM/11 - Laboratório de Cirurgia Cardiovascular e Fisiopatologia da Circulação, Hospital das Clínicas, Faculdade de Medicina
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- Long-Term and Sustained Therapeutic Results of a Specific Promonocyte Cell Formulation in Refractory Angina: ReACT (R) (Refractory Angina Cell Therapy) Clinical Update and Cost-Effective Analysis(2015) HOSSNE JR., Nelson Americo; CRUZ, Eduardo; BUFFOLO, Enio; COIMBRA, Anna Carolina Teixeira de Siqueira Mac Dowell; MACHADO, Janaina; GOLDENBERG, Regina Coeli dos Santos; REGAZZI, Germana; AZEVEDO, Silvia; INVITTI, Adriana Luckow; BRANCO, Joao Nelson Rodrigues; OLIVEIRA, Jose Salvador Rodrigues de; STOLF, Noedir Antonio Groppo; MILLER, Leslie W.; SANBERG, Paul R.Mononuclear stem cells have been studied for their potential in myocardial ischemia. In our previous published article, ReACT (R) phase I/II clinical trial, our results suggest that a certain cell population, promonocytes, directly correlated with the perceived angiogenesis in refractory angina patients. This study is ReACT's clinical update, assessing long-term sustained efficacy. The ReACT phase HAM noncontrolled, open-label, clinical trial enrolled 14 patients with refractory angina and viable ischemic myocardium, without ventricular dysfunction, who were not suitable for myocardial revascularization. The procedure consisted of direct myocardial injection of a specific mononuclear cell formulation, with a certain percentage of promonocytes, in a single series of multiple injections (24-90; 0.2 ml each) into specific areas of the left ventricle. Primary endpoints were Canadian Cardiovascular Society Angina Classification (CCSAC) improvement at the 12-month follow-up and ischemic area reduction (scintigraphic analysis) at the 12-month follow-up, in correlation with ReACT's formulation. A recovery index (for patients with more than 1 year follow-up) was created to evaluate CCSAC over time, until April 2011. Almost all patients presented progressive improvement in CCSAC beginning 3 months (p =0.002) postprocedure, which was sustained at the 12-month follow-up (p =0.002), as well as objective myocardium ischemic area reduction at 6 months (decrease of 15%, p <0.024) and 12 months (decrease of 100%, p <0.004) The recovery index (n=10) showed that the patients were graded less than CCSAC 4 for 73.9 +/- 24.2% over a median follow-up time of 46.8 months. After characterization, ReACT's promonocyte concentration suggested a positive correlation with CCSAC improvement (r=-0.575, p =0.082). Quality of life (SF-36 questionnaire) improved significantly in almost all domains. Cost-effectiveness analysis showed decrease in angina-related direct costs. Refractory angina patients presented a sustained long-term improvement in CCSAC and myocardium ischemic areas after the procedure. The long-term follow-up and strong improvement in quality of life reinforce effectiveness. Promonocytes may play a key role in myocardial neoangiogenesis. ReACT dramatically decreased direct costs.
- Comparative Analysis of the Complications of 5347 Endomyocardial Biopsies Applied to Patients After Heart Transplantation and With Cardiomyopathies: A Single-center Study(2012) FIORELLI, A. I.; BENVENUTI, L.; AIELO, V.; COELHO, A. Q.; PALAZZO, J. F.; ROSSENER, R.; BARRETO, A. C. P.; MADY, C.; BACAL, F.; BOCCHI, E.; STOLF, N. A. G.Introduction. Endomyocardial biopsy (EMB) plays an important role in allograft surveillance to screen an acute rejection episode after heart transplantation (HT), to diagnose an unknown cause of cardiomyopathies (CMP) or to reveal a cardiac tumor. However, the procedure is not risk free. Objective. The main objective of this research was to describe our experience with EMB during the last 33 years comparing surgical risk between FIT versus no-HT patients. Method. We analyzed retrospectively the data of 5347 EMBs performed from 1978 to 2011 (33 years). For surveillance of acute rejection episodes after HT we performed 3564 (66.7%), whereas 1777 (33.2%) for CMP diagnosis, and 6 (1.0%) for cardiac tumor identification. Results. The main complications due to EMB were divided into 2 groups to facilitate analysis: major complications associated with potential death risk, and minor complications. The variables that showed a significant difference in the HT group were as follows: tricuspid Injury (.0490) and coronary fistula (.0000). Among the no-HT cohort they were insufficient fragment (.0000), major complications (.0000) and total complications (.0000). Conclusions. EMB can be accomplished with a low risk of complications and high effectiveness to diagnose CMP and rejection after HT. However, the risk is great among patients with CMP due to their anatomic characteristics. Children also constitute a risk group for EMB due to their small size in addition to the heart disease. The risk of injury to the tricuspid valve was higher among the HT group.
- Comparative Analysis of the Performance of Various Crystalloid Cardioplegic Solutions on Myocardial Protection After Prolonged Cold Ischemia(2011) LIMA, M. L.; FIORELLI, A. I.; GOMES, O. M.; PINHEIRO, B. B.; SILVA, M. A. F. Da; PORTO, L. A. B. J.; NOVAES, L.; STOLF, N. A. G.; SOUZA, D. R.Introduction. The quality and effectiveness of myocardial protection are fundamental problems to expand the use of and consequently good outcomes of donated hearts for transplantation. Objective. The purpose of this investigation was to compare the cardioprotective effects of Krebs-Henseleit, Bretschneider-HTK, St Thomas, and Celsior solutions using a modified nonrecirculating Langendorff column model of isolated perfused rat heart during prolonged cold storage. Materials and Methods. After removal 36 rat hearts underwent isolated perfusion into a Langendorff apparatus using Krebs-Henseleit solution for a 15-minute period of recovery; we excluded organs that did not maintain an aortic pressure above 100 m Hg. Subsequently, we equally distributed the hearts into four groups according to the cardioprotection solution; group 1, Krebs-Henseleit (control); group II, Bretschneider-HTK; group III, St Thomas; and group IV, Celsior. Each heart received the specific cardioplegic solution at 10 C for 2-hour storage at 20 C, before a 15 minutes perfusion with Krebs-Henseleit solution for recovery and stabilization. After 60 additional minutes of perfusion, every 5 minutes we determined heart rate (HR), coronary flow (CF), left ventricular systolic pressure (LVSP), and positive and negative peak of the first derivative of left ventricular pressure (+dP/dt and dP/dt, respectively). Results. Comparative analysis by Turkey's test showed the following performances among the groups at 60 minutes of reperfusion: HR: II = IV > III > I; CF: II = IV > I = III; LVSP: IV > I = II = III; +dP/dt: IV > I = II = III; and dP/dt: IV = II > I = II. Conclusion. Cardioprotective solutions generally used in clinical practice are not able to avoid hemodynamic alterations in hearts exposed to prolonged ischemia. Celsior solution showed better performance than Bretschneider-HTK, St Thomas, and Krebs-Henseleit.
conferenceObject Comparative Study between Cavopulmonary Anastomosis Associated with Left Ventricular Assist Device Support and Biventricular Circulatory Assistance in Acute Biventricular Failure(2012) SANTOS, L. A. S.; MOREIRA, L. F. P.; BENICIO, A.; CESTARI, I.; MATTOS JR., E.; STOLF, N. G.Purpose: Right ventricular failure during left ventricular assist device (LVAD) support can result in severe hemodynamic compromise with high mortality. This study investigated the acute effects of cavopulmonary anastomosis on LVAD performance and right ventricular myocardial compromise in comparison with biventricular circulatory support, in a model of severe biventricular failure. Methods and Materials: LVAD support was performed by means of centrifugal pump implantation in 21 anesthetized pigs (20-30 kg) with biventricular failure obtained by ventricular fibrillation induction. Animals were randomized to be submitted to modified cavopulmonary anastomosis, to biventricular circulatory support or to control group. They were maintained under circulatory support and hemodynamic monitoring for 3h. Venous lactate and cytokines serum levels were also determined. Endocardium samples of the ventricles were collected and analyzed by electronic microscopy. Results: Ventricular fibrillation was responsible for acute LVAD performance impairment after 180 min in the control group. Cavopulmonary anastomosis resulted in non-significant improvement of LVAD pump flow in relation to control group (+55±14 ml/kg/min, p=0.072), while animals under biventricular support maintained higher LVAD flow performance (+93±17 ml/kg/min, p=0.012). Mean arterial pressure remained constant only in biventricular group (p<0.001), which also presented significant decrease of right atrial and ventricular pressures. Similar increases in lactate and cytokines levels were observed in the three groups. Ultrastructural analysis documented the presence of higher levels of myocardial mitochondrial swelling in control group (p=0.018). Conclusions: Concomitant use of cavopulmonary anastomosis during LVAD support in a pig model of severe biventricular failure resulted in non-significant improvement of hemodynamic performance and it did not effectively replace the use of biventricular support.- Risk Factor Analysis of Late Survival After Heart Transplantation According to Donor Profile: A Multi-Institutional Retrospective Study of 512 Transplants(2012) FIORELLI, A. I.; BRANCO, J. N.; DINKHUYSEN, J. J.; OLIVEIRA JUNIOR, J. L.; PEREIRA, T. V.; DINARDI, L. F. L.; SANTOS, M. M.; DIAS, R. R.; PEREIRA, L. A.; STOLF, N. A. G.Introduction. Patients with terminal heart failure have increased more than the available organs leading to a high mortality rate on the waiting list. Use of Marginal and expanded criteria donors has increased due to the heart shortage. Objective. We analyzed all heart transplantations (HTx) in Sao Paulo state over 8 years for donor profile and recipient risk factors. Method. This multi-institutional review collected HTx data from all institutions in the state of Sao Paulo, Brazil. From 2002 to 2008 (6 years), only 512 (28.8%) of 1777 available heart donors were accepted for transplantation. All medical records were analyzed retrospectively; none of the used donors was excluded, even those considered to be nonstandard. Results. The hospital mortality rate was 27.9% (n = 143) and the average follow-up time was 29.4 +/- 28.4 months. The survival rate was 55.5% (n = 285) at 6 years after HTx. Univariate analysis showed the following factors to impact survival: age (P = .0004), arterial hypertension (P = .4620), norepinephrine (P = .0450), cardiac arrest (P = .8500), diabetes mellitus (P = .5120), infection (P = .1470), CKMB (creatine kinase MB) (P = .8694), creatinine (P = .7225), and Na+ (P = .3273). On multivariate analysis, only age showed significance; logistic regression showed a significant cut-off at 40 years: organs from donors older than 40 years showed a lower late survival rates (P = .0032). Conclusions. Donor age older than 40 years represents an important risk factor for survival after HTx. Neither donor gender nor norepinephrine use negatively affected early survival.
- Tricuspid Valve Injury After Heart Transplantation Due to Endomyocardial Biopsy: An Analysis of 3550 Biopsies(2012) FIORELLI, A. I.; COELHO, G. H. B.; AIELLO, V. D.; BENVENUTI, L. A.; PALAZZO, J. F.; SANTOS JUNIOR, V. P.; CANIZARES, B.; DIAS, R. R.; STOLF, N. A. G.Introduction. Tricuspid regurgitation (TR) is the most commonly valvular dysfunction found after heart transplantation (HTx). It may be related to endomyocardial biopsy (EMB) performed for allograft rejection surveillance. Objective. This investigation evaluated the presence of tricuspid valve tissue fragments obtained during routine EMB performed after HTx and its possible effect on short-term and long-term hemodynamic status. Method. This single-center review included prospectively collected and retrospectively analyzed data. From 1985 to 2010, 417 patients underwent 3550 EMB after HTx. All myocardial specimens were reviewed to identify the presence of tricuspid valve tissue by 2 observers initially and in doubtful cases by a third observer. The echocardiographic and hemodynamic parameters were only considered for valvular functional damage analysis in cases of tricuspid tissue inadvertently removed during EMB. Results. The 417 HTx patients to 3550 EMB, including 17,550 myocardial specimens. Tricuspid valve tissue was observed in 12 (2.9%) patients corresponding to 0.07% of the removed fragments. The echocardiographic and hemodynamic parameters of these patients before versus after the biopsy showed increased TR in 2 cases (2/12; 16.7%) quantified as moderate without progression in the long term. Only the right atrial pressure showed a significant increase (P = .0420) after tricuspid injury; however, the worsening of the functional class was not significant enough in any of the subjects. Thus, surgical intervention was not required. Conclusions. Histological evidence of chordal tissue in EMB specimens is a real-world problem of relatively low frequency. Traumatic tricuspid valve injury due to EMB rarely leads to severe valvular regurgitation; only a minority of patients develop significant clinical symptoms. Hemodynamic and echocardiographic alterations are also less often observed in most patients.
- Long-Term Pulmonary Vascular Reactivity After Orthotopic Heart Transplantation by the Biatrial Versus the Bicaval Technique(2011) FIORELLI, A. I.; SANTOS, R. H. B.; OLIVEIRA JR., J. L.; SILVA, M. A. F. Da; SANTOS JR., V. P. dos; REGO, F. M. P.; SOUZA, G. E.; BACAL, F.; BOCCHI, E. A.; STOLF, N. A. G.Introduction. Advantages of the bicaval versus the biatrial technique have been reported, emphasizing atrial electrical stability and less tricuspid regurgitation. Objective. To analyze the impact of the surgical technique on long-term pulmonary pressures, contractility, and graft valvular behavior after heart transplantation. Methods. Among 400 orthotopic heart transplantation recipients from 1985 to 2010, we selected 30 consecutive patients who had survived beyond 3 years. The biatrial versus bicaval surgical technique groups included 15 patients each. Their preoperative clinical characteristics were similar. None of the patients displayed a pulmonary vascular resistance or pulmonary artery pressure over 6U Wood or 60 mm Hg, respectively. We evaluated invasive hemodynamic parameters during routine endomyocardial biopsies. Two-dimensional echocardiographic parameters were obtained from routine examinations. Results. There were no significant differences regarding right atrial pressure, systolic pulmonary artery pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, cardiac index, systolic blood pressure, left ventricular ejection fraction, and mitral regurgitation (P > .05). Tricuspid regurgitation increased significantly over the 3 years of observation only among the biatrial group (P = .0212). In both groups, the right atrial pressure, pulmonary wedge capillary pressure, transpulmonary gradient, and pulmonary vascular resistance decreased significantly (P < .05) from the pre- to the postoperative examination. In both groups cardiac index and systemic blood pressure increased significantly after transplantation (P < .05). Comparative analysis of the groups only showed significant differences regarding right atrial pressure and degree of tricuspid regurgitation; the bicaval group showing the best performance. Conclusions. Both surgical techniques ensure adequate left ventricular function in the long term; however, the bicaval technique provided better trends in hemodynamic performance, as well as a lower incidence and severity of tricuspid valve dysfunction.
- Successful Endomyocardial Biopsy Guided by Transthoracic Two-Dimensional Echocardiography(2011) FIORELLI, A. I.; COELHO, G. B.; SANTOS, R. H. B.; OLIVEIRA JR., J. L.; AIELO, V.; BENVENUTI, L.; OLIVEIRA, A. S.; SILVA, M. A. F. Da; CHIZZOLA, P. R.; COSTA, R.; MATHIAS JR., W.; BACAL, F.; BOCCHI, E. A.; STOLF, N. A. G.Introduction. Two-dimensional (2-D) echocardiography is an excellent alternative method to perform endomyocardial biopsies (EB) in special situations, mainly when the patient is in a critical state and cannot go to the catheterization laboratory or when there are contraindications to the use of fluoroscopy as in the pregnancy. Objective. This single-center experience analyzed the last 25 years use of an EB technique guided by echocardiography realized at the bedside on critical patients. Methods. From 1985 to 2010, we performed 76 EB guided by 2-D echocardiography on 59 patients, among whom 38 (64.4%) were critically ill with examinations at the bedside; among 10 (16.9%) subjects, the procedure was carried out simultaneously with fluoroscopy for safety's sake during the learning period. In addition, 8 (13.6%) were unavailable for fluoroscopy, and 3 (5.1%) required a hybrid method due to an intracardiac tumor. Results. The main adverse effects included local pain (n = 4, 5.6%); difficult out successful puncture due to previous biopsies (n = 4, 5.6%); local hematoma without major consequences (n = 3, 4.2%); failed but ultimately successful puncture on the first try due to previous biopsies or (n = 3, 4.2%); obesity and immediate postoperative period with impossibility to pass the bioptome into the right ventricle; however 2 days later the procedure was repeated successfully by echocardiography (n = 1, 1.4%). All myocardial specimens displayed suitable size. There were no undesirable extraction effects on the tricuspid valve tissue. In this series, there was no case of death, hemopericardium, or other major complication as a direct consequence of the biopsy. Conclusion. 2-D echocardiography is a special feature to guide EB is mainly in critically ill patients because it can be performed at the bedside without additional risk or disadvantages of fluoroscopy. The hybrid method associating 2-D echocardiography and fluoroscopy allows the procedure in different situations such as intracardiac tumor cases.
article 2 Citação(ões) na Scopus Estudo experimental comparativo do enxerto homólogo pulmonar tratado pelo processo L-Hydro com o homoenxerto pulmonar a fresco(2011) REY, Nei Antonio; MOREIRA, Luiz Felipe Pinho; CHEUNG, David T.; CASAGRANDE, Ivan Sergio Joviano; BENVENUTI, Luiz Alberto; STOLF, Noedir Antonio GroppoObjective: In an effort to make available homografts preserved in a simpler and less costly way, we evaluated the polyethyleneglycol, L-Hydro (LH) method, that consists in the controlled extraction of antigenic substances and the incorporation of anti-inflammatory and anti-thrombotic agent. Methods: We substituted the pulmonary trunk in ten ovines, seven received LH treated pulmonary homografts and three, fresh pulmonary homografts, orthotopically implanted and followed-up for 320 days. Ovines where evaluated by means of laboratory tests, echocardiographic exams. At the 320 days, were euthanized, hemodynamic, radiology, macroscopic, optic/electronic microscopic, scanning/transmission evaluations were performed. Results were analyzed by Student t test of independent samples for continuous data, by variance analysis of repeated measures, and by Fisher exact test for categorical data. Results: We couldn't establish relevant differences in clinical evolution and laboratory tests between groups. Echocardiogram revealed difference in pulmonary medium gradient, which was significant 10 months follow-up, higher in the control group. Radio logic and macroscopic evaluations didn't established differences. In the optic/electronic microscopic evaluation, liner and interstitial cells were equally found in both groups. The cell liner percent calculated in both groups was similar. Cellularity nodules were observed only infresh homograft group. Conclusions: These data indicate that both groups presented similar clinical/hemodynamic performances. The LH group's echocardiogram presented a better performance. It also presented histological evidences of interstitial and endothelial cell repopulation. In the macro/optic and electronic microscopic analysis, group L-H presented macroscopy/histological structure and ultra-structural similar to the fresh group, with the exception of nodules with higher interstitial cellularity, present only in the fresh homograft group.- Heart Transplantation in 107 Cases of Chagas' Disease(2011) FIORELLI, A. I.; SANTOS, R. H. B.; OLIVEIRA JR., J. L.; LOURENCO-FILHO, D. D.; DIAS, R. R.; OLIVEIRA, A. S.; SILVA, M. F. A. da; AYOUB, F. L.; BACAL, F.; SOUZA, G. E. C.; BOCCHI, E. A.; STOLF, N. A. G.Introduction. Chagas' disease is endemic in South America. Objective. This research reviewed the experience with cardiac transplantation in Chagas' disease, emphasizing reactivation, immunosuppression, and mortality. Methods. Over 25 years from March 1985 to March 2010, 107/409 (26.2%) patients with Chagas' disease underwent heart transplantation, patients including 74 (71.1%) men and 72 (67.2%), in functional class IV with 33 (30.8%) on vasopressors and 17 (10.7%) on mechanical circulatory support. Results. The diagnosis of disease reactivation was performed by identifying the parasite in the myocardium (n = 23; 71.8%) in the subcutaneous tissue (n = 8; 25.0%), in blood (n = 11; 34.3%), or in central nervous tissue (n = 1; 3.1%). Hospital mortality was 17.7% (n = 19) due to infection (n = 6; 31.5%), graft dysfunction (n = 6; 31.5%), rejection (n 4; 21.1%), or sudden death (n = 2; 10.5%). Late mortality was 27 (25.2%) cases, which were distributed as: rejection (n = 6; 22.2%), infection (n = 6; 22.2%), (n = lymphoma 4; 14.8%), sarcoma (n = 2; 7.4%), for constrictive pericarditis (n = 2; 7.4%) reactivation of Chagas' disease in the central nervous system (n = 1; 7.1%). Conclusions. Transplantation in Chagas' disease has peculiar problems that differ from other etiologies due to the possibility of disease reactivation and the increased possibility of emergence of cancers. However, transplantation is the only treatment able to modify the natural progression of the disease in its terminal phase. Early diagnosis and rapid introduction of benzonidazole reverses the histological patterns. Immunosuppression, especially steroids, predisposes to the development of cancer and disease reactivation.