Clinical profile of patients enroled in a cell therapy trial for severe coronary artery disease.

AIMS AND OBJECTIVES: To compare the clinical profile of patients included in a clinical trial of autologous bone marrow cells as an adjunctive therapy to coronary artery bypass grafting with that of patients undergoing routine coronary artery bypass grafting. BACKGROUND: The therapeutic potential of autologous bone marrow cells has been explored in the treatment of severe coronary artery disease. There are few data regarding the clinical and socio-economic profile of patients included in clinical trials using bone marrow cell. DESIGN: Case-control study. METHOD: Sixty-seven patients (61 SD 9) years, 82% men) with multivessel coronary artery disease were divided into two groups: patients in the bone marrow cell group (n = 34) underwent incomplete coronary artery bypass grafting + intramyocardial injection of autologous bone marrow cells (lymphomonocytic fraction -2.0 (SD 0.2 x 10(8)) cells/patient) in the ischaemic, non-revascularised myocardium, whereas patients in the coronary artery bypass grafting group (n = 33) underwent routine bypass surgery. Demographics, socio-economic status, clinical and echocardiographic data were collected. Statistical analysis included the Fisher's exact test (categorical variables) and the Student's t-test (continuous variables). RESULTS: There were no significant differences between groups regarding age, gender, BMI, heart rate, blood pressure and echo data. There was a greater prevalence of obesity (65 vs. 33%; OR = 3.7 [1.3-10.1]), of previous myocardial infarction (68 vs. 39%; OR = 3.2 [1.2-8.8]) and prior revascularisation procedures (59 vs. 24%; OR = 4.5 [1.6-12.7]) in the autologous bone marrow cells group and of smokers in the coronary artery bypass grafting group (51 vs. 23%; OR = 3.5 [1.2-10.4]). CONCLUSIONS: Patients included in this clinical trial of autologous bone marrow cells for severe coronary artery disease presented a greater prevalence of myocardial revascularisation procedures, indicating a more severe clinical presentation of the disease. Fewer smokers in this group could be attributable to life style changes after previous cardiovascular events and/or interventions. RELEVANCE TO CLINICAL PRACTICE: The knowledge of the clinical profile of patients included in cell therapy trials may help researchers in the identification of patients that may be enroled in future clinical trials of this new therapeutic strategy.

Five-year follow-up of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease.

BACKGROUND: Despite routine use of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI), no conclusive evidence exists that either modality is superior to medical therapy (MT) alone for treating multivessel coronary artery disease with stable angina and preserved ventricular function. METHODS AND RESULTS: The primary end points were total mortality, Q-wave myocardial infarction, or refractory angina requiring revascularization. The study comprised 611 patients randomly assigned to undergo CABG (n=203), PCI (n=205), or MT (n=203). At the 5-year follow-up, the primary end points occurred in 21.2% of patients who underwent CABG compared with 32.7% treated with PCI and 36% receiving MT alone (P=0.0026). No statistical differences were observed in overall mortality among the 3 groups. In addition, 9.4% of MT and 11.2% of PCI patients underwent repeat revascularization procedures compared with 3.9% of CABG patients (P=0.021). Moreover, 15.3%, 11.2%, and 8.3% of patients experienced nonfatal myocardial infarction in the MT, PCI, and CABG groups, respectively (P<0.001). The pairwise treatment comparisons of the primary end points showed no difference between PCI and MT (relative risk, 0.93; 95% confidence interval, 0.67 to 1.30) and a significant protective effect of CABG compared with MT (relative risk, 0.53; 95% confidence interval, 0.36 to 0.77). CONCLUSIONS: All 3 treatment regimens yielded comparable, relatively low rates of death. MT was associated with an incidence of long-term events and rate of additional revascularization similar to those for PCI. CABG was superior to MT in terms of the primary end points, reaching a significant 44% reduction in primary end points at the 5-year follow-up of patients with stable multivessel coronary artery disease.

Intramyocardial injection of autologous bone marrow cells as an adjunctive therapy to incomplete myocardial revascularization--safety issues.

OBJECTIVES: To determine the safety of intramyocardial injection of autologous bone marrow cells in patients undergoing surgical myocardial revascularization (CABG) for severe coronary artery disease. INTRODUCTION: There is little data available regarding the safety profile of autologous bone marrow cells injected during surgical myocardial revascularization. Potential risks include arrythmias, fibrosis in the injected sites and growth of non-cardiac tissues. METHODS: Ten patients (eight men) were enrolled; they were 59+/-5 years old with limiting angina and were non-optimal candidates for complete CABG. Bone marrow cells (1.3+/-0.3x10(8)) were obtained prior to surgery, and the lymphomonocytic fraction (CD34+ =1.8+/-0.3%) was separated by density gradient centrifugation. During surgery, bone marrow cells were injected in non-grafted areas of ischemic myocardium. During the first year after surgery, the patients underwent laboratory tests, cardiac imaging, and 24-hour ECG monitoring. RESULTS: Injected segments: inferior (n=7), anterior (n=2), septal (n=1), apical (n=1), and lateral (n=1) walls. Except for a transient elevation of C-reactive protein at one month post-surgery (P=0.01), laboratory tests results were within normal ranges; neither complex arrhythmias nor structural abnormalities were detected during follow-up. There was a reduction in functional class of angina from 3.6+/-0.8 (baseline) to 1.2+/-0.4 (one year) (P<0.0001). Also, patients had a significant decrease in the ischemic score assessed by magnetic resonance, not only globally from 0.65+/-0.14 (baseline) to 0.17+/-0.05 (one year) (P=0.002), but also in the injected areas from 1.11+/-0.20 (baseline) to 0.34+/-0.13 (one year) (P=0.0009). CONCLUSIONS: Intramyocardial injection of bone marrow cells combined with CABG appears to be safe. Theoretical concerns with arrhythmias and/or structural abnormalities after cell therapy were not confirmed in this safety trial.

Coronary revascularization (surgical or percutaneous) decreases mortality after the first year in diabetic subjects but not in nondiabetic subjects with multivessel disease: an analysis from the Medicine, Angioplasty, or Surgery Study (MASS II).

BACKGROUND: It is currently unknown whether revascularization procedures are associated with an improvement in mortality among diabetic subjects, as compared with a more conservative medical treatment. METHODS AND RESULTS: In MASS II, a total of 611 patients with stable multivessel coronary disease were randomly assigned to medical treatment, surgery, or angioplasty. From these, 190 patients had diabetes (medical, 75 patients; angioplasty, 56 patients; surgery, 59 patients) and comprised the present study population. Mortality rates were analyzed for the entire 5 years of follow-up. Separate analyzes were also performed for mortality at 2 time intervals: during the first year and after the first year of follow-up. We calculated the probability of death conditional on surviving to the start of the interval analyzed. The cumulative 5-year mortality as well as the mortality during the first year of follow-up was not significantly different among treatment groups, both for diabetic and for nondiabetic subjects. Also, during years 2 to 5, the mortality of the 3 treatment groups was not different for nondiabetic subjects. Among diabetic subjects, however, patients randomized to angioplasty or surgery had a significantly lower mortality between years 2 and 5 than those allocated to medical treatment (P=0.039). CONCLUSIONS: Surgery, angioplasty, and medical treatment appear to be associated with similar mortality rates for non-diabetic subjects. For diabetic subjects, however, coronary revascularization (percutaneous or surgical) significantly decreased the risk of death after the first year and up to 5 years, compared with medical treatment alone.

Dynamic regulation of MTHFR mRNA expression and C677T genotype modulate mortality in coronary artery disease patients after revascularization.

INTRODUCTION: A large body of evidence links plasma homocysteine (Hcy) concentrations and cardiovascular disease. A common MTHFR polymorphism (C677T) leads to a variant with reduced activity and associated with increased Hcy levels. Coronary surgery precipitates a significant and sustained increase in the blood concentrations of Hcy and elevated levels of plasma Hcy have been associated to saphenous vein (SV) graft disease after CABG. However, the effects of MTHFR genotypes in the incidence of cardiovascular events after CABG have not been investigated prospectively. Here, we investigate whether MTHFR gene variants are associated with an increased cardiovascular risk in individuals submitted to CABG. We also propose a molecular mechanism to explain our findings. METHODS: We performed MTHFR C677T genotypes in 558 patients with two or three vessel-disease and normal left ventricular function prospectively followed in the MASS II Trial, a randomized study to compare treatments for multivessel CAD and preserved left ventricle function. Follow-up time was 5 years. Survival curves were calculated with the Kaplan-Meier method, and evaluated with the log-rank statistic. We assessed the relationship between baseline variables and the composite end-point of death, myocardial infarction and refractory angina using a Cox proportional hazards survival model. Finally, using an ex-vivo organ culture we have reproduced the arterialization of SV implants by culturing human SV either under venous hemodynamic condition (flow: 5 mL/min; no pressure) or arterial hemodynamic condition (flow: 50 mL/min; pressure: 80 mm Hg) for 1 day. MTHFR gene expression was quantified by real time RT-PCR in 15 SV from different individuals in both experimental conditions. RESULTS: There were no significant differences among individuals within each genotype group for baseline clinical characteristics. A statistically significant association between the TT genotype, associated with increased serum levels of Hcy, and cardiovascular mortality after 5 years was verified (p=0.007) in individuals submitted to CABG surgery. In addition, MTHFR TT genotype was still significantly associated with a 4.4 fold increased risk in cardiovascular outcomes (p=0.01) even after adjustment of a Cox multivariate model for age, sex, hypertension, diabetes, LDL, HDL, triglycerides, and number of diseased vessels in this population. Finally, a significant reduction in MTHFR gene expression was demonstrated in human SV when submitted to an arterial hemodynamic condition (p=0.02). CONCLUSIONS: There is a dynamic regulation of MTHFR gene expression during the arterialization process of human saphenous vein grafts resulting in lower levels of gene expression when in an arterial hemodynamic condition. In addition, the C677T MTHFR functional variant is associated with a worse outcome in individuals submitted to CABG. Taken together, these data suggest an important role of Hcy metabolism in individuals after CABG.

Single-lung ventilation with contralateral lung deflation: a simplified method for multivessel off-pump coronary artery bypass grafting.

There are many new alternative methods of minimally invasive myocardial revascularization that can be applied in selected patients who have multivessel coronary artery disease. However, these techniques often require new and expensive equipment. Most multivessel myocardial revascularization is performed via median sternotomy and involves the use of a conventional endotracheal tube. Both lungs are ventilated, and frequently the left pleural cavity is opened. In contrast, single-lung deflation naturally moves the mediastinum within the thorax toward the collapsed lung, without the need to open the pleural cavities. Herein, we describe a simple alternative procedure that facilitates off-pump multivessel coronary artery bypass grafting via complete median sternotomy: single-lung ventilation with contralateral lung deflation. This technique better exposes the more distal right and circumflex coronary artery branches with or without the opening of the pleural cavities.

Effectiveness of the maze procedure using cooled-tip radiofrequency ablation in patients with permanent atrial fibrillation and rheumatic mitral valve disease.

BACKGROUND: Although the Cox-Maze III procedure is effective for treating permanent atrial fibrillation (AF), its high complexity limits its use. The Saline-Irrigated Cooled-tip Radiofrequency Ablation (SICTRA) System is an alternative source of energy used to ablate AF. The aim of this study was to evaluate the effectiveness of the SICTRA for the treatment of permanent AF in patients with rheumatic mitral valve (MV) disease. METHODS AND RESULTS: Between February 2002 and April 2003, 70 patients with permanent AF and rheumatic MV disease were randomly assigned to undergo a modified Maze III procedure using SICTRA associated with MV surgery (group A) or MV surgery alone (group B). Groups A and B were similar in terms of baseline characteristics. The in-hospital mortality rate was 2.3% (1 death) in group A versus 0% (no deaths) in group B (P>0.99). The additional time required for the left-sided radiofrequency ablation in group A was 14.2+/-5.1 minutes and for right-sided ablation was 12.3+/-4.2 minutes. The mean postoperative follow-up periods were 13.8+/-3.4 and 11.5+/-7.3 months, respectively, in groups A and B. The overall mid-term survival rate was 95.1% in group A and 92.8% in group B (P>0.99). The cumulative rates of sinus rhythm were 79.4% in group A and 26.9% in group B (P=0.001). Doppler echocardiography documented biatrial transport function in 90.3% of group A patients in sinus rhythm. CONCLUSIONS: The SICTRA is effective for treating permanent AF associated with rheumatic MV disease.

Co-infection ratios versus inflammation, growth factors and progression of early atheromas.

Mycoplasma pneumoniae (MP) and Chlamydophila pneumoniae (CP) antigens are encountered in complicated atheromas and may be implicated in the diversity of atherosclerotic lesions. Mycoplasma can downregulate the immune system, altering levels of inflammation, which may favor the proliferation of other co-infectious agents. In the present study we analyze whether initially stable human atheromas exhibit different ratios of MP/CP antigens compared to ongoing atheromatous lesions. Two groups were examined for the presence of inflammatory cells, macrophages, growth factors and infectious agents: Group I (GI), n=16, early stable atheromas, <4 CD68(+) macrophages/400 x field, showing a normal distribution and a fibrous cap; Group II (GII), n=14, growing atheromas, > or =4 CD68+ cells/400 x field, lacking a fibrous cap, showing a non-normal macrophage distribution. The amounts of CP (but not MP) antigens and lymphocytes in GI were significantly lower than in GII. MP/CP ratios were higher in GI. MP correlated with CP and PDGFB in GI (r=0.79 and r=0.83, p<0.001), but not in GII (r=-0.4 and r=-0.08, p=0.81). MP and CP antigens are already present in early atheromas, and a higher MP/CP ratio correlates with increased growth factors, lower inflammation and plaque stability.

Long-term follow up of the Biocor porcine bioprosthesis in the mitral position.

BACKGROUND AND AIM OF THE STUDY: The study aim was to review the long-term results of mitral valve replacement (MVR) with the Biocor porcine bioprosthesis, in order to investigate patient survival and valve-related complications. METHODS: Data were presented for 546 patients (320 females, 226 males; mean age 49.2 +/- 17.1 years) who underwent MVR with the Biocor porcine bioprosthesis between March 1983 and December 2000. Preoperatively, rheumatic fever was present in 42.3% of patients. Associated procedures were performed in 179 patients (32.7%), and myocardial revascularization in 54 (9.9%). Preoperatively, 41.9% of patients were in NYHA class IV. Postoperative follow up was conducted by telephone interviews, questionnaires, or examination of hospital records. RESULTS: The hospital mortality was 9.5% (n=52); of these patients, 30 died after their first MVR and 22 after mitral reoperation. Mortality after isolated MVR was 7.6%. The total follow up was 2,148.9 patient-years, and actuarial survival was 45.0 +/- 15.8% at 15 years. Freedom from structural valve deterioration (SVD) was 51.8 +/- 13.8% for patients aged <50 years, 88.7 +/- 5.1% for those aged 51-60 years, and 84.0 +/- 9.8% for those aged 61-80 years. The incidence of prosthetic valve endocarditis was low, with 88.8 +/- 6.1% non-recurrence in 15 years. Freedom from reoperation was 33.9 +/- 10.4%, and from thromboembolism was 82.3 +/- 15.0%. Freedom from valve-related mortality was 80.7 +/- 12.5% during a 15-year period. CONCLUSION: The 15-year clinical results with the Biocor porcine bioprosthesis in the mitral position were excellent in a young, predominantly rheumatic, patient population which, preoperatively, was in a grave clinical condition. The incidence of valve-related complications was low, as was that of SVD in patients aged >50 years.

Relative cost comparison of treatments for coronary artery disease: the First Year Follow-Up of MASS II Study.

BACKGROUND: Prior comparisons of costs following CABG and PTCA have demonstrated higher initial costs after CABG but following PTCA, recurrent symptoms and repeat revascularization result in increased late costs and over time their costs equilibrate. The MASS II trial provides an opportunity to compare the costs of CABG and PTCA in addition to a strategy of medical therapy. METHODS: We studied the 611 patients of MASS II [Medical (203), Angioplasty (205), or Surgery (203) Study], a randomized study to compare treatments for multivessel CAD and preserved left ventricle function. The costs were: CABG 10,650.00 US dollars; PTCA 6400.00 US dollars; new AMI hospitalization AMI 2550 US dollars; angiography not followed-up of PTCA 1900.00 US dollars; and medication 1200.00 US dollars for medical, and 1000.00 US dollars for the other groups. We did adjustment for average event-free time, and angina-free proportion. The statistical analysis carried out was chi-square, t test, and analysis of variance. RESULTS: After 1 year, 49% Medical, 79% PTCA, and 88% CABG became angina-free; P<0.0001. There were 26 coronary angiograms (5 medical, 17 PTCA, and 4 CABG), 23 AMI (8 medical, 17 PTCA, and 6 CABG; P=0.03); PTCA was performed in 7 Medical, 17 PTCA, and 1 CABG, (P=0.0003), CABG was performed in 15 Medical, 8 PTCA, and zero CABG; P=0.002. The event-free and event and angina-free-costs in the first year were 2453.50 US dollars and 5006.32 US dollars for Medical; 10348,43 US dollars; and 13,099.31 US dollars for PTCA; and 12,404.21 US dollars and 14,095.09 US dollars for CABG group. An increase from expected costs of 317%, 77%, and 21%, respectively. CONCLUSIONS: PTCA effective costs were similar to CAGB costs, Medical treatment presented the lowest cost, and however, the greatest increment, and CABG presented the most stable costs.

The medicine, angioplasty, or surgery study (MASS-II): a randomized, controlled clinical trial of three therapeutic strategies for multivessel coronary artery disease: one-year results.

OBJECTIVES: We sought to evaluate the relative efficacies of three possible therapeutic strategies for patients with multivessel coronary artery disease (CAD), stable angina, and preserved ventricular function. BACKGROUND: Despite routine use of coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI), there is no conclusive evidence that either one is superior to medical therapy (MT) alone for the treatment of multivessel CAD. METHODS: The primary end point was defined as cardiac mortality, Q-wave myocardial infarction (MI), or refractory angina requiring revascularization. All data were analyzed according to the intention-to-treat principle. RESULTS: A total of 611 patients were randomly assigned to either a CABG (n = 203), PCI (n = 205), or MT (n = 203) group. The one-year survival rates were 96.0% for CABG, 95.6% for PCI, and 98.5% for MT. The rates for one-year survival free of Q-wave MI were 98% for CABG, 92% for PCI, and 97% for MT. After one-year follow-up, 8.3% of MT patients and 13.3% of PCI patients underwent to additional interventions, compared with only 0.5% of CABG patients. At one-year follow-up, 88% of the patients in the CABG group, 79% in the PCI group, and 46% in the MT group were free of angina (p < 0.0001). CONCLUSIONS: Medical therapy for multivessel CAD was associated with a lower incidence of short-term events and a reduced need for additional revascularization, compared with PCI. In addition, CABG was superior to MT for eliminating anginal symptoms. All three therapeutic regimens yielded relatively low rates of cardiac-related deaths.

Immediate ischemic preconditioning based on somatosensory evoked potentials seems to prevent spinal cord injury following descending thoracic aorta cross-clamping.

OBJECTIVE: Delayed ischemic preconditioning has demonstrated neuroprotective effects in spinal cord ischemia. We investigated the effects of immediate ischemic preconditioning based on somatosensory evoked potentials monitoring in a model of spinal cord injury due descending thoracic aorta occlusion in dogs. METHODS: Twenty-one dogs were submitted to spinal cord ischemia induced by descending thoracic aorta cross-clamping for 45 min. Control group underwent only the aortic cross-clamping (n=7), group A underwent one cycle of ischemic preconditioning (n=7) and group B underwent three equal cycles of ischemic preconditioning (n=7), immediately before the aortic cross-clamping. Ischemic preconditioning cycles were determined by somatosensory evoked potentials monitoring. Neurologic evaluation was performed according to the Tarlov score at 72 h of follow-up. The animals were then sacrificed and the spinal cord harvested for histopathology. RESULTS: Aortic pressures before and after the occluded segment were similar in the three groups. Ischemic preconditioning periods corresponded to a mean ischemic time of 3+/-1 min and a mean recovery time of 7+/-2 min. Severe paraplegia was observed in three animals in Control group, in four in group A and in none in group B. Tarlov scores of group B were significantly better in comparison to the Control group (P=0.036). Histopathologic examination showed severe neuronal necrosis in the thoracic and lumbar gray matter in animals who presented paraplegia. CONCLUSIONS: Immediate repetitive ischemic preconditioning based on somatosensory evoked potentials monitoring seems to protect spinal cord during descending aorta cross-clamping, reducing paraplegia incidence.

Mitral valve annuloplasty with a bovine pericardial strip--18-year results.

PURPOSE: Prosthetic annuloplasty rings are currently used in mitral reconstruction. Posterior annuloplasty with a bovine pericardial strip is a technique largely used in the Heart Institute of University of São Paulo Medical School. The purpose of the study was to analyze the late results of mitral valve repair with posterior annuloplasty using a bovine pericardial strip. METHODS: Between January 1984 and December 2002, 273 patients underwent mitral valve repair with posterior pericardial annuloplasty in the Heart Institute of University of São Paulo Medical School. One hundred and forty four (52.7%) were women and ages ranged between 1 and 76 years (38.3 +/- 21.1). Rheumatic fever was present in 52.0% of the patients. Associated techniques were employed in 26.0% of the patients, and the most frequent was chordal shortening (9.2%). RESULTS: Hospital mortality was 3.3% (9 patients), with the major cause being low cardiac output (6 patients). Actuarial survival was 55.1% +/- 16.8% in 18 years. During the 18-year follow-up: patients were free from the following: reoperation (59.1% +/- 13.9%, (percent +/- Standard Error), thromboembolism (97.4% +/- 2.3%), hemolysis (99.2% +/- 0.2%), and endocarditis (99.6% +/- 1.0%). In the late follow-up period, 83.9% were classified as New York Heart Association functional class I. CONCLUSIONS: Late results with mitral valve repair with posterior annuloplasty using a bovine pericardial strip were satisfactory. The technique is feasible, reproducible, and cost effective.

Comparative study of the L-hydro process and glutaraldehyde preservation.

Commercial bioprosthetic heart valves are commonly preserved in glutaraldehyde and are cytotoxic to host cells, preventing spontaneous endothelialization. The aim of this study was to demonstrate the potential for in vivo endothelialization of bioprostheses treated by the L-Hydro process which consists of mild extraction of antigenic substances and incorporation of antiinflammatory and antithrombotic agents. Seven stented porcine heart valves treated by the L-Hydro process and 3 glutaraldehyde-fixed porcine heart valves were implanted in the mitral position in juvenile sheep. The valves were evaluated by echocardiography, angiography, histology, and histochemistry. No hemodynamic differences were observed, but scanning and transmission electron microscopy showed nearly complete coverage by endothelial cells of all leaflets in the L-Hydro-treated valves after 5 months of implantation. The endothelial cells were in direct contact with the underlying collagen and expressed von Willebrand-related antigens. The surfaces of the glutaraldehyde-treated valves were covered by fibrin, macrophages, calcium, and thrombotic material; only sparse endothelial cells were observed and contact with the underlying tissue was incomplete. These data indicate that L-Hydro-treated porcine valves are capable of inducing spontaneous endothelialization.

Likelihood of left main coronary artery compression based on pulmonary trunk diameter in patients with pulmonary hypertension.

PURPOSE: In patients with pulmonary hypertension, extrinsic compression of the left main coronary artery by a dilated pulmonary trunk may cause angina, left ventricular ischemia, and sudden death. We assessed coronary artery compression in relation to pulmonary trunk diameter and other demographic, echocardiographic, hemodynamic, and scintigraphic variables. METHODS: Thirty-six patients (aged 15 to 86 years) with pulmonary hypertension, either idiopathic or associated with congenital heart disease, were enrolled. Left main coronary artery compression was defined angiographically as > or =50% obstruction associated with downward displacement of the vessel. Pulmonary trunk and aortic diameters were measured by transthoracic echocardiography. RESULTS: Twenty-six patients had angina, of whom 7 had left coronary artery compression. Compression was related to pulmonary trunk diameter (P = 0.002) and to the ratio of pulmonary trunk diameter to aortic diameter (P = 0.02). Compression was not seen at pulmonary artery diameters <40 mm; among 19 patients with values > or =40 mm, the rate was 37%. Similarly, compression did not occur at pulmonary trunk to aortic diameter ratios <1.21; among 27 patients with ratios > or =1.21, the rate was 26%. CONCLUSION: In pulmonary hypertension, noninvasive measurement of pulmonary trunk diameter may be helpful in determining the likelihood of left coronary artery compression and in selecting patients for diagnostic coronary angiography.

First use of hypertonic saline dextran in children: a study in safety and effectiveness for atrial septal defect surgery.

Hypertonic saline dextran (7.5% NaCl + 6% Dextran-70) has been used in adults in several studies and shown beneficial effects in hypovolemic shock, trauma, cardiogenic shock, and cardiac surgery. There have never been studies of this solution in children. This work studies its effect in children undergoing surgery for the correction of atrial septal defects. Twenty-five children underwent correction of atrial septal defect using cardiopulmonary bypass with bloodless priming. Children were divided in five groups and each received an incremental hypertonic saline dextran dose of 0.1, 0.5, 1.0, 2.0, and 4.0 mL/kg, 5 min before the beginning of cardiopulmonary bypass. Collected data were fluid balance, amount of bleeding, blood/derivative transfusion occurrence, plasma sodium, and hematocrit. Patients were divided into low-dose (0-1 mL/kg) and high-dose (2-4 mL/kg) groups. Analysis of variance was used to determine differences in blood loss between groups. The fluid balance and blood/derivative requirements were compared through Student's t test and Fisher's exact test (2-tail), respectively. All patients were discharged from hospital with corrected atrial septal defect. No hypertonic saline dextran-related complications occurred. There were no differences in the amount of bleeding. The high-dose group exhibited a significant decrease in fluid balance and in blood/derivative requirements in comparison with the low-dose group. In this study, the use of hypertonic saline dextran in the pediatric population submitted to cardiopulmonary bypass is safe and does not raise the amount of bleeding. Its effective doses produce negative fluid balance and reduce blood/derivative requirements.

Reversible pulmonary trunk banding. II. An experimental model for rapid pulmonary ventricular hypertrophy.

OBJECTIVE: An experimental model with a reversible pulmonary trunk banding device was developed with the aim of inducing rapid ventricular hypertrophy. The device consists of an insufflatable cuff connected to a self-sealing button. METHODS: The right ventricles of 7 young goats (average weight, 8.7 kg) were submitted to systolic overload and evaluated according to the hemodynamic, echocardiographic, and morphologic aspects. Baseline biopsy specimens were taken from the myocardium for microscopic analysis. The device was implanted on the pulmonary trunk and inflated so that a 0.7 right ventricular/left ventricular pressure ratio was achieved. Echocardiographic and hemodynamic evaluations were performed every 24 hours. Systolic overload was maintained for 96 hours. The animals were then killed for morphologic study. Another 9 goats (average weight, 7.7 kg) were used for control right ventricular weight. RESULTS: The systolic right ventricular/pulmonary trunk pressure gradient varied from 10.1 +/- 4.3 mm Hg (baseline) to 60.0 +/- 11.0 mm Hg (final). Consequently, the right ventricular/left ventricular pressure ratio increased from 0.29 +/- 0.06 to 1.04 +/- 0.14. The protocol group showed a 74% increase in right ventricular mass when compared with the control group. Serial 2-dimensional echocardiography showed a 66% increase in right ventricular wall thickness. There was a 24% increase in the mean myocyte perimeter, and the myocyte area increased 61%. CONCLUSIONS: The device is easily adjustable percutaneously, enabling right ventricular hypertrophy in 96 hours of gradual systolic overload. This study suggests that the adjustable pulmonary trunk banding might provide better results for the 2-stage Jatene operation and for the failed atrial switch operations to convert to the double-switch operation.

Reevaluation of long-term outcomes of dynamic cardiomyoplasty.

BACKGROUND: Palliative procedures have been proposed for treatment of dilated cardiomyopathies. This study analyzes long-term outcomes of 43 patients who underwent dynamic cardiomyoplasty. METHODS: Patients were in New York Heart Association class III (n = 35) or IV (n = 8) before the procedure. Hospital mortality was 2.2%, and patients were followed for 44 +/- 33 months. Thirty-nine patients completed the skeletal muscle adaptation period, and the muscle flaps were stimulated to contract in concert with every cardiac beat (n = 27) or with every other beat (n = 12). RESULTS: One-year event-free survival was 81.3% +/- 5.9%; 2-year, 65.1% +/- 7.2%; 5-year, 34.7% +/- 7.2%; and 9-year, 10.8% +/- 5.3%. Causes of late deaths were equally divided between progressive heart failure and arrhythmia-related events. Multivariable Cox proportional hazard regression identified that functional class IV, high pulmonary vascular resistance, and muscle flap stimulation synchronized to every cardiac beat were independent predictors of poor event-free survival. The same factors were associated with the occurrence of progressive heart failure, but none was a predictor of arrhythmia-related deaths. Five-year survival of patients maintained with the muscle flap stimulated at every other cardiac beat was 58.3% +/- 14.2%. Skeletal muscle stimulation protocols also influenced the long-term behavior of left ventricular ejection fraction. CONCLUSIONS: Long-term results of dynamic cardiomyoplasty are limited by the patient's preoperative condition and by a high incidence of sudden cardiac death. These results may be improved using modified skeletal muscle stimulation protocols and cardioverter-defibrillator implantation, while maintaining dynamic cardiomyoplasty as an option for selected patients.

Minimally invasive single-vessel coronary artery bypass with the internal thoracic artery and early postoperative angiography: midterm results of a prospective study in 120 consecutive patients.

BACKGROUND: This prospective study was undertaken to determine the role of the minimally invasive direct coronary artery bypass with early postoperative angiography and midterm follow-up in 120 consecutive patients with single-vessel coronary artery disease. METHODS: Minimal access (6 to 10 cm), without complete sternotomy and no cardiopulmonary bypass, was used. The lesions were located at the proximal left anterior descending coronary artery in 95% of the patients. Routine coronary angiography was performed before discharge. RESULTS: Postoperative angiography was performed in 104 (90.4%) of those 115 patients who had coronary revascularization concluded by the mini-access method. The internal thoracic artery patency rate was 98.1% (95.2% grade A). Two (1.7%) patients presented with perioperative myocardial infarction, which led to the single in-hospital death (0.8%). Of the remaining 119 patients, 113 (95.0%) were asymptomatic. The event-free probability was 94.9% and the actuarial survival was 98.3% with 42 months of follow-up. CONCLUSIONS: For selected patients with single-vessel coronary artery disease and no major myocardial dysfunction, minimally invasive direct coronary artery bypass is a safe operation and a less invasive alternative to conventional coronary artery bypass grafting.

Right internal thoracic artery remodeling 18 years after circumflex system grafting.

A 64-year-old man with left main coronary artery disease underwent myocardial revascularization. The left internal thoracic artery (LITA) was sutured to the left anterior descending artery, and the right internal thoracic artery (RITA) was sutured to the obtuse marginal artery. Eighteen years later, angina reoccurred. Catheterization revealed that both the coronary and the left subclavian arteries were occluded and that a patent RITA graft was maintaining the cardiac blood supply. The RITA graft evaluation revealed increased lumen diameters, suggestive of remodeling. The LITA was subsequently disconnected and sutured to the aorta as a free graft in order to restore appropriate myocardial blood flow. This case emphasizes the benefits of using a live graft for left coronary system grafting, which include long-term patency and flow-dependent remodeling.