Fernando Oswaldo Dias Rangel

Transendocardial, Autologous Bone Marrow Cell Transplantation for Severe, Chronic Ischemic Heart Failure

Background—This study evaluated the hypothesis that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease could safely promote neovascularization and improve perfusion and myocardial contractility. Methods and Results—Twenty-one patients were enrolled in this prospective, nonrandomized, open-label study (first 14 patients, treatment; last 7 patients, control). Baseline evaluations included complete clinical and laboratory evaluations, exercise stress (ramp treadmill), 2D Doppler echocardiogram, single-photon emission computed tomography perfusion scan, and 24-hour Holter monitoring. Bone marrow mononuclear cells were harvested, isolated, washed, and resuspended in saline for injection by NOGA catheter (15 injections of 0.2 cc). Electromechanical mapping was used to identify viable myocardium (unipolar voltage ≥6.9 mV) for treatment. Treated and control patients underwent 2-month noninvasive follow-up, and treated patients alone underwent a 4-month invasive follow-up according to standard protocols and with the same procedures used as at baseline. Patient population demographics and exercise test variables did not differ significantly between the treatment and control groups; only serum creatinine and brain natriuretic peptide levels varied in laboratory evaluations at follow-up, being relatively higher in control patients. At 2 months, there was a significant reduction in total reversible defect and improvement in global left ventricular function within the treatment group and between the treatment and control groups (P =0.02) on quantitative single-photon emission computed tomography analysis. At 4 months, there was improvement in ejection fraction from a baseline of 20% to 29% (P =0.003) and a reduction in end-systolic volume (P =0.03) in the treated patients. Electromechanical mapping revealed significant mechanical improvement of the injected segments (P <0.0005) at 4 months after treatment. Conclusions—Thus, the present study demonstrates the relative safety of intramyocardial injections of bone marrow–derived stem cells in humans with severe heart failure and the potential for improving myocardial blood flow with associated enhancement of regional and global left ventricular function.

Improved Exercise Capacity and Ischemia 6 and 12 Months After Transendocardial Injection of Autologous Bone Marrow Mononuclear Cells for Ischemic Cardiomyopathy

Background—We recently reported the safety and feasibility of autologous bone marrow mononuclear cell (ABMMNC) injection into areas of ischemic myocardium in patients with end-stage ischemic cardiomyopathy. The present study evaluated the safety and efficacy of this therapy at 6- and 12-month follow-up. Methods and Results—Twenty patients with 6- and 12-month follow-up (11 treated subjects; 9 controls) were enrolled in this prospective, nonrandomized, open-label study. Complete clinical and laboratory evaluations as well as exercise stress (ramp treadmill), 2-dimensional Doppler echocardiography, single-photon emission computed tomography (SPECT) perfusion scanning, and 24-hour Holter monitoring were performed at baseline and follow-up. Transendocardial delivery of ABMMNCs was performed with the aid of electromechanical mapping to identify viable myocardium. Each patient received 15 ABMMNC injections of 0.2 mL each. At 6 and 12 months, total reversible defect, as measured by SPECT perfusion scanning, was significantly reduced in the treatment group as compared with the control group. At 12 months, exercise capacity was significantly improved in the treatment group. This improvement correlated well with monocyte, B-cell, hematopoietic progenitor cell, and early hemapoietic progenitor cell phenotypes. Conclusions—The 6- and 12-month follow-up data in this study suggest that transendocardial injection of ABMMNCs in patients with end-stage ischemic heart disease may produce a durable therapeutic effect and improve myocardial perfusion and exercise capacity.

Terapia da insuficiência cardíaca avançada ajustada por objetivos hemodinâmicos obtidos pela monitorização invasiva

OBJECTIVE To assess advanced heart failure (HF) treatment in relation to reduction of ventricular filling pressures, with the use of greater doses of vasodilators, through invasive hemodynamic monitoring. METHODS Nineteen advanced HF patients were studied, in whom Swan-Ganz catheter was inserted to direct administration of diuretic intravenously (IV) and sodium nitroprusside, with the aim of significantly reduce ventricular filling pressures. After achieving such objective or 48 hours, oral drugs were introduced until venous medicines were removed, keeping hemodynamic benefit. RESULTS From 19 patients studied, 16 (84%) were of male sex. The average age was 66 +/- 11.4 years old; average ejection fraction was 26 +/- 6.3%; 2 patients (10.5%) showed functional class (FC) III and 17 (89.5%), FC IV. There was a decrease of pulmonary artery occlusion pressure from 23 +/- 11.50 mmHg to 16 +/- 4.05 mmHg (p = 0.008), of systemic vascular resistance index from 3,023 +/- 1,153.71 dynes/s/cm-5/m(2) to 1,834 +/- 719.34 dynes/s/cm-5/m(2) (p = 0.0001) and an increase of cardiac index from 2.1 +/- 0.56 l/min/m(2) to 2.8 +/- 0.73 l/min/m(2) (p = 0.0003). A subgroup with hypovolemia was identified. CONCLUSION It was possible to reduce ventricular filling pressures to significantly lower values, obtaining a significant improvement of cardiac index, systemic vascular resistance index and pulmonary artery mean pressure, by using significantly higher doses of vasodilators.OBJECTIVE: To assess advanced heart failure (HF) treatment in relation to reduction of ventricular filling pressures, with the use of greater doses of vasodilators, through invasive hemodynamic monitoring. METHODS: Nineteen advanced HF patients were studied, in whom Swan-Ganz catheter was inserted to direct administration of diuretic intravenously (IV) and sodium nitroprusside, with the aim of significantly reduce ventricular filling pressures. After achieving such objective or 48 hours, oral drugs were introduced until venous medicines were removed, keeping hemodynamic benefit. RESULTS: From 19 patients studied, 16 (84%) were of male sex. The average age was 66 ± 11.4 years old; average ejection fraction was 26 ± 6.3%; 2 patients (10.5%) showed functional class (FC) III and 17 (89.5%), FC IV. There was a decrease of pulmonary artery occlusion pressure from 23 ± 11.50 mmHg to 16 ± 4.05 mmHg (p = 0.008), of systemic vascular resistance index from 3,023 ± 1,153.71 dynes/s/cm-5/m2 to 1,834 ± 719.34 dynes/s/cm-5/m2 (p = 0.0001) and an increase of cardiac index from 2.1 ± 0.56 l/min/m2 to 2.8 ± 0.73 l/min/m2 (p = 0.0003). A subgroup with hypovolemia was identified. CONCLUSION: It was possible to reduce ventricular filling pressures to significantly lower values, obtaining a significant improvement of cardiac index, systemic vascular resistance index and pulmonary artery mean pressure, by using significantly higher doses of vasodilators.

864-2 One-year follow-up of transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy

Emerson C. Perin, Hans F. Dohmann, Radovan Borojevic, Suzana A. Silva, Andre L. Sousa, Guilherme V. Silva, Joao A. Assad, Claudio T. Mesquita, Luciano Belem, Roberto Esporcatte, Fernando O. Rangel, Antonio C. Carvalho, Isabel Rossi, William K. Vaughn, Hans J. Dohmann, James T. Willerson, Texas Heart Institue, Houston, TX, Pro-Cardiaco Hospital, Rio de Janeiro, BrazilBackground: Limited treatment options exist for patients with end-stage ischemic heartfailure (HF) not amenable to revascularization. We evaluated the effect of transendocar-dial (TE) delivery of Autologous Bone Marrow Mononuclear Cells (ABMMC) in patientswith severe HF.Methods: Ten patients (mean age 58 ± 11 yrs) were studied. All patients had LV dysfunc-tion secondary to ischemic cardiomyopathy. Bone marrow (50 ml) was aspirated andABMMCs were isolated. TE injections were performed using the Myo-star catheter(NOGA, Biosense) to target hibernating myocardium guided electromechanical mapping(EMM). Patients were evaluated by ramp treadmill and Holter monitoring at baseline, 2months , 6 months and one year. ANOVA was utilized.Results: Exercise testing showed gradual and continous improvement in METs(p=0.0005) and VO2max (p=0.002) over time . METs improved from 4.9 at baseline to6.7 at 2 months to 7.4 at 6 months up to 7.9 at one year follow-up. There was no differ-ence in total number of PVCs over the follow-up period. Ramp treadmill findings ofVO2max are presented in figure 1.Conclusion: In this small number of patients receiving TE injection of ABMMC and fol-lowed up to one year there was no evidence of significant arrhythmias and there was sus-tained improvement in exercise capacity. Future studies are needed to further clarify therole of stem-cell therapy in the treatment of ischemic cardiomyopathy.

Improvement in global and segmental left ventricular contractility following autologous bone marrow cell transplantation in humans with severe ischemic heart failure

Background: Although diastolic heart failure is common, the factors that predict mortalsty have not been clearly defined. Methods: We studied 988 patients (59% men) with documented heart failure and ejection fraction > 45% who were enrolled and prospectively followed in the Digitalis Investigation Group (DIG) trial. During 3.1 years of follow-up, there were 231 deaths (23%). Results: The average age was 87210 years, and the average ejection fraction was Ss+_S%. There were 285 patients with diabetes (29%) and 557 with fschemlc head disease (57%). In univariable analyses, predictors of death included older age, increasing serum creatinine, decreasing body mass index, and presence of diabetes (Figure shows quartiles or presence of these versus 3-year Kaplan-M&r death rates). 874-5 Improvement in Global and Segmental Left Ventricular Contractility Following Autologous Bone Marrow Cell Transplantation in Humans With Severe lschemic Heart Failure

Natriuretic Peptide and Clinical Evaluation in the Diagnosis of Heart Failure Hemodynamic Profile: Comparison with Tissue Doppler Echocardiography

Background Physical examination and B-type natriuretic peptide (BNP) have been used to estimate hemodynamics and tailor therapy of acute decompensated heart failure (ADHF) patients. However, correlation between these parameters and left ventricular filling pressures is controversial. Objective This study was designed to evaluate the diagnostic accuracy of physical examination, chest radiography (CR) and BNP in estimating left atrial pressure (LAP) as assessed by tissue Doppler echocardiogram. Methods Patients admitted with ADHF were prospectively assessed. Diagnostic characteristics of physical signs of heart failure, CR and BNP in predicting elevation (> 15 mm Hg) of LAP, alone or combined, were calculated. Spearman test was used to analyze the correlation between non-normal distribution variables. The level of significance was 5%. Results Forty-three patients were included, with mean age of 69.9 ± 11.1years, left ventricular ejection fraction of 25 ± 8.0%, and BNP of 1057 ± 1024.21 pg/mL. Individually, all clinical, CR or BNP parameters had a poor performance in predicting LAP ≥ 15 mm Hg. A clinical score of congestion had the poorest performance [area under the receiver operating characteristic curve (AUC) 0.53], followed by clinical score + CR (AUC 0.60), clinical score + CR + BNP > 400 pg/mL (AUC 0.62), and clinical score + CR + BNP > 1000 pg/mL (AUC 0.66). Conclusion Physical examination, CR and BNP had a poor performance in predicting a LAP ≥ 15 mm Hg. Using these parameters alone or in combination may lead to inaccurate estimation of hemodynamics.