Joäo Ricardo Sant'Anna

Randomized study of surgical isolation of the pulmonary veins for correction of permanent atrial fibrillation associated with mitral valve disease

OBJECTIVE Chronic permanent atrial fibrillation is often due to mitral valve disease. The Cox maze procedure is the gold standard for treating this arrhythmia. Simpler techniques and ablation methods should have their efficacy tested in clinical practice. Our objective was to evaluate the effectiveness of surgical pulmonary vein isolation as compared with the Cox maze procedure. METHODS Sixty patients were randomly assigned to control group, modified maze group (Cox maze III), and surgical isolation of the pulmonary veins (SPVI) group from July 1999 to October 2004. All patients had mitral valve lesions treated concomitantly. Preoperative characteristics were similar between groups. RESULTS There were 4 deaths: 3 in the Cox maze group and 1 in the SPVI group (P = .31). The Cox maze group presented longer times of extracorporeal circulation and myocardial ischemia (P < .001). The relative risk of late postoperative development of atrial fibrillation was 0.07 in the SPVI group (P < .001; 95% confidence intervals: 0.02-0.27) and 0.195 in the Cox maze group (P = .002; 95% confidence intervals: 0.07-0.56) as compared with the control group. No difference was found between the SPVI and Cox maze groups concerning prevention of atrial fibrillation recurrence (relative risk: 0.358; P = .215; 95% confidence intervals: 0.08-1.67). CONCLUSIONS The modified Cox maze procedure and surgical pulmonary vein isolation were similarly effective in restoring sinus or regular rhythm in permanent atrial fibrillation associated with mitral valve disease. These results favor the adoption of surgical isolation as a preferable technique, simpler and equally effective in controlling atrial fibrillation. The results also can bring further information for understanding the mechanisms involved in origins and treatment of chronic permanent atrial fibrillation.

VEGF gene therapy for angiogenesis in refractory angina: phase I/II clinical trial

OBJECTIVE Safety, feasibility and early myocardial angiogenic effects evaluation of transthoracic intramyocardial phVEGF165 administration for refractory angina in no option patients. METHODS Cohort study, in which 13 patients with refractory angina under optimized clinical treatment where included, after cineangiograms had been evaluated and found unfeasible by surgeon and interventional cardiologist. Intramyocardial injections of 5 mL solution containing plasmidial VEGF165 where done over the ischemic area of myocardium identified by previous SPECT/Sestamibi scan. Evaluations included a SPECT scan, stress test, Minnesota QOL questionnaire and NYHA functional class and CCS angina class determinations. RESULTS There were no deaths or new interventions during the study period. There were no significant variations in SPECT scans, QOL scores and stress tests results during medical treatment in the included patients. After the 3rd post operative month, there was improvement in SPECT segmental scores, SSS (18.38 ± 7.51 vs. 15.31 ± 7.29, P = 0.003) and SRS (11.92 ± 7.49 vs. 8.53 ± 6.68, P = 0.002). The ischemic area extension, however, had non-significant variation (23.38 ± 13.12% vs. 20.08 ± 13.88%, P = 0.1). Stress tests METs varied from 7.66 ± 4.47 pre to 10.29 ± 4.36 METs post-op (P = 0.08). QOL score improved from 48.23 ± 18.35 pre to 30.15 ± 20.13 post-op points (P = 0.02). NYHA class was 3.15 ± 0.38 pre vs. 1.77 ± 0.83 post-op (P = 0.001) and angina CCS class, 3.08 ± 0.64 vs. 1.77 ± 0.83 (P = 0.001). CONCLUSIONS Intramyocardial VEGF165 therapy for refractory angina, in this small trial of no option patients, resulted feasible and safe. Early clinical and scintilographic data showed improvements in symptoms and myocardial perfusion, with regression of ischemia severity in treated areas.

Autologous transplantation of bone marrow mononuclear stem cells by mini-thoracotomy in dilated cardiomyopathy: technique and early results

CONTEXT AND OBJECTIVES There are few studies concerning bone marrow mononuclear cell (BMMC) transplantation in cases of nonischemic dilated cardiomyopathy. This study describes a novel technique of BMMC transplantation and the results up to one year after the procedure. DESIGN AND SETTING This was a case series to evaluate the safety and viability of the procedure, at Instituto de Cardiologia do Rio Grande do Sul. METHODS Nine patients with symptomatic dilated cardiomyopathy, functional class III/IV and left ventricular ejection fraction (LVEF) < 35% received BMMC (9.6 +/- 2.6 x 107 cells) at 20 sites in the ventricular wall, by means of thoracotomy of length 5 cm in the fifth left intercostal space. Echocardiograms and nuclear magnetic resonance (NMR) were performed. RESULTS There were no major complications. The functional class results for the first six patients (preoperatively and at two, four, eight and twelve-month follow-ups, respectively) were: [IV-2, III-4] to [I-5, II-1] to [I-3, II-3] to [I-2, II-3] and [I-2, II-3]. Echocardiograms showed LVEF: 25.9 +/- 8.2; 32.9 +/- 10.4; 29.4 +/- 7.2; 25.1 +/- 7.9; 25.4 +/- 6.8% (p = 0.023); and % left ventricular (LV) fiber shortening: 12.6 +/- 4.4; 16.4 +/- 5.4; 14.3 +/- 3.7; 12.1 +/- 4.0; 12.2 +/- 3.4% (p = 0.021). LV performance variation seen on NMR was non-significant. CONCLUSION Intramyocardial transplantation of BMMC in dilated cardiomyopathy cases is feasible and safe. There were early improvements in symptoms and LV performance. Medium-term evaluation revealed regression of LV function, although maintaining improved functional class.

Risk factors for hospital mortality in valve replacement with mechanical prosthesis

OBJECTIVE Identification of risk factors for cardiac surgery can improve surgical results. Our aim is to identify factors related to increased hospital mortality for patients who underwent mechanical cardiac prosthesis implant. METHODS Prospective study with retrospective data acquirement study including 335 consecutive patients who underwent at least one implant of St. Jude Medical mechanical prosthesis between December 1994 and September 2005 at the Cardiology Institute of RS. Valve implants were 158 (47.1%) in aortic position, 146 (43.6%) in mitral and 31 (9.3%) in aortic and mitral. The following characteristics were analyzed in relation to hospital death: gender, age, body mass index, NYHA functional class, ejection fraction, type of valve lesion, hypertension, diabetes mellitus, serum creatinine, preoperative arrhythmias, prior heart surgery, CABG surgery, concomitant tricuspid valve surgery and operative priority (elective, urgent or emergent). Logistical regression was used to analyze data and odds-ratio was calculated for individual factors. RESULTS During the follow-up there were 13 (3.88%) deaths. In-hospital mortality risk was associated with serum creatinine (P<0.05), ejection fraction < 30% (P<0.001), mitral valve lesion (P<0.05), concomitant CABG surgery (P<0.01), prior cardiac surgery (P<0.01) and reoperation (P<0.01). Increased odd-ratio were related to previous cardiac surgery (5.36; IC95% 0.94-30.56), combined revascularization (5.28; IC95% 1.51-18.36), valvar reoperation (4.69; IC95% 0.93-23.57) and concomitant tricuspid annuloplasty (3.72; IC95% 0.75-18.30). CONCLUSION The mortality rate is within the parameters found in the literature, identifying recognized factors which neutralization by changes in surgical indication and medical management may enable risk reduction.

High Doses of Vascular Endothelial Growth Factor 165 Safely, but Transiently, Improve Myocardial Perfusion in No-Option Ischemic Disease

UNLABELLED Gene therapy can induce angiogenesis in ischemic tissues. The aim of this study was to assess safety, feasibility, and results, both clinical and on myocardial perfusion, of gene therapy in refractory angina. This was a phase I/II, prospective, temporal-controlled series, clinical trial. Thirteen patients were maintained for minimum 6 months under optimized clinical management, and then received intramyocardial injections of 2000 μg plasmid vascular endothelial growth factor 165 and were followed by single-photon emission computed tomography (SPECT), treadmill tests, Minnesota quality of life questionnaire (QOL), and New York Heart Association (NYHA) functional plus Canadian Cardiovascular Society (CCS) angina classifications. There were no deaths, early or late. During the optimized clinical treatment, we observed worsening of rest ischemia scores on SPECT (p<0.05). After treatment, there was a transitory increase in myocardial perfusion at the third-month SPECT under stress (pre-operative [pre-op] 18.38 ± 7.51 vs. 3 months 15.31 ± 7.30; p<0.01) and at the sixth month under rest (pre-op 13.23 ± 7.98 vs. 6 months: 16.92 ± 7.27; p<0.01). One year after, there were improvements in treadmill test steps (pre-op 2.46 ± 2.07 vs.12 months 4.15 ± 2.23; p<0.01) and oxygen consumption (pre-op 7.66 ± 4.47 vs.12 months 10.89 ± 4.65; p<0.05), QOL (pre-op 48.23 ± 18.35 vs.12 months 28.31 ± 18.14; p<0.01) scores, and CCS (pre-op 3 [3-3.5] vs.12 months 2 [1-2.5]; p<0.01) and NYHA (pre-op 3 [3-3] vs. 2 [2-2] vs. 12 months 2 [1-2]; p<0.01) classes. Gene therapy demonstrated to be feasible and safe in this advanced ischemic cardiomyopathy patient sample. There were improvements in clinical evaluation parameters, and a transitory increase in myocardial perfusion detectable by SPECT scintigraphy. CLINICAL TRIAL REGISTRATION NCT00744315 http://clinicaltrials.gov/

Global contractility increment in nonischemic dilated cardiomyopathy after free wall-only intramyocardial injection of autologous bone marrow mononuclear cells: an insight over stem cells clinical mechanism of action.

Bone marrow mononuclear cells (BMMC) effects have been investigated in small series of nonischemic dilated cardiomyopathy (NIDC). Left ventricular myocardial contractility improvements occur, but doubt remains about their mechanism of action. We compared contractility changes in areas treated (free wall) and nontreated (septal wall) with BMMC, in selected patients who have showed significant ventricular improvement after free wall-only intramyocardial stem cells injection. From 15 patients with functional class III/IV (NYHA) and LVEF inferior to 35%, who received 9.6 ± 2.6 × 107 BMMC divided into 10 points over the left ventricular free wall, 7 (46.7%) showed LVEF relative improvement greater than 15%. Those patients were selected for further contractility study. BMMC were collected from iliac bone and isolated with Ficoll-Hypaque. Magnetic resonance imaging was used to measure the systolic thickening of the septal (nontreated) and free wall (treated) before injection and 3 months postoperatively. Mean systolic septal wall thickening increased from 0.46 to 1.23 mm (an absolute 0.77 ± 1.3 mm and relative 167.4% increase) and in the free wall from 1.13 to 1.87 mm (an absolute 0.74 ± 1.5 mm and relative increase of 65.5%). There was no difference in the rate of absolute or relative systolic thickening between the two walls (p = 0.866 and 1.0, respectively), when cells were injected only in the left ventricular free wall. BMMC transplantation in nonischemic dilated cardiomyopathy can improve ventricular function by an overall effect, even in areas that are not directly injected. This finding favors the existence of a diffuse mechanism of action, rather than a local effect, and should be reminded when the pathophysiology of stem cells is considered.

Influências temporais nas características e fatores de risco de pacientes submetidos a revascularização miocárdica

OBJECTIVE To compare the clinical and surgical profile between two groups of patients submitted to Myocardial Revascularization (MCR) surgery at the Instituto de Cardiologia of Rio Grande do Sul with a ten year interval, to observe its influence upon MCR hospital mortality and to verify the predictability of this result using the risk score. METHODS A retrospective cohort study involving 307 patients who underwent MCR surgery within a six month period during 1991/92 (INITIAL group, n=153) or 2001/02 (CURRENT group, n=154). Demographic characteristics, heart disease, comorbidities and surgical events were analyzed to compare the groups and to define the hospital mortality risk score (based on the Cleveland Clinic method). RESULTS The CURRENT group was older, had more severe heart condition (functional class, incidence of heart failure and number of vessels with severe lesions) and a greater prevalence of comorbidities. The INITIAL group had a higher prevalence of nonelective surgery. Both groups had similar mean risk scores (2.8 +/- 3.1 for INITIAL and 2.2 +/- 2.5 for CURRENT) and hospital mortality rates (3.3% and 1.9% respectively). These figures are comparable to those for reported by Cleveland Clinic (for a risk score of 3 the predicted mortality range between 2.0 %; using a confidence level of 95% the predicted mortality is between 0 and 4.3%; and actual mortality confirmed by the study was 3.4%). CONCLUSION Patients currently submitted to MCR are older and in worse clinical condition (heart and systemic) than those operated on ten years ago; however, the risk scores and hospital mortality rates were slightly higher in the INITIAL group. The higher number of nonelective surgical interventions could have contributed to this. A risk score can be used to identify patients that require a higher level of care and to predict surgical outcomes.

Técnica cirúrgica simplificada pode ser eficaz no tratamento da fibrilação atrial crônica secundária a lesão valvar mitral

INTRODUCTION: Atrial fibrillation, nowadays, has been treated surgically by the maze procedure and its modifications. However, there is some evidence that points to the pulmonary vein ostia as trigger point for this arrhythmia. We postulate a surgical approach of pulmonary vein isolation or left atrial isolation in order to treat this disease. In this study we show the initial results of this technique in patients with chronic atrial fibrillation associated with mitral valve disease. MATERIAL AND METHODS: Seven patients were operated on by pulmonary vein isolation (IVP) and compared to the past results of the 57 patients in which the maze procedure had been done (Cox 3). RESULTS: Age - 49±8 years vs. 49±11 years (IVP vs. Cox 3), 71% and 72% (IVP vs. Cox 3) were female. Left atrium size was 5.5±0.7 cm vs. 6.0±1.1 cm (IVP vs. Cox 3). Ventricular EF 63±10% vs. 64±6% (IVP vs. Cox 3). Extracorporeal circulation time 91±33 min vs.104±29 min (IVP vs. Cox 3). Aortic cross-clamping 71±23 min vs. 83±26 min (IVP vs. Cox 3). Cardiac rhythm: sinusal / atrial n(%): 6(86) vs. 46(80) (IVP vs. Cox 3). Cardiac pace rhythm n(%):1 (14) vs. 4 (7) (IVP vs. Cox 3). Atrial fibrillation n(%):0 vs. 7 (13) (IVP vs. Cox 3). CONCLUSIONS: The initial results show sinus rhythm restoration and its maintenance. We have already started a double-blind randomized trial between these two surgical techniques.

Gene therapy with VEGF 165 for angiogenesis in experimental acute myocardial infarction

OBJECTIVE: Evaluate coronary angiogenic response to transmural injection of plasmid encoding VEGF 165 in acute myocardial infarction (AMI) zones in a canine model. METHODS: The heart of eleven dogs was exposed and AMI was induced by occlusion of the diagonal branch of anterior descending coronary artery. For each of 10 selected points in the infarction area and its peripheral zone injections of 1 ml of saline solution (control group: five dogs) or 1 ml of plasmid encoding VEGF 165 solution (200 µg/ml) (VEGF group: six dogs) were introduced. Tecnecium myocardial scintigraphy was performed immediately after animal recovery and 14 days later to evaluate the myocardial perfusion. The animals were sacrificed and the hearts were submitted to a histological study of the infarcted area, peripheral zone and normal posterior ventricular wall, to evaluate the number of arterioles and capillaries. RESULTS: Immediate modifications in myocardial perfusion found in scintigraphic studies were similar in both groups. In the second evaluation at 14 days, hypoperfusion of ischemic area had recovered by 70% to 90% when compared to the day of AMI. Histologic evaluation of the peripheral area of AMI indicated a larger number of vessels in the VEGF group when compared to controls (mean: 123.81 + 21.48 and 40 + 6.13, p < 0.01, respectively). This increase resulted mainly from an increase in the number of capillaries (97.5 + 16.04 in the VEGF group and 22.18 + 3,25 in control group, p < 0.01), as the number of arterioles did not increase significantly. In the VEGF group, a comparison in the number of vessels of the AMI peripheral area and normal myocardium revealed a non-significant increase of vessels in the ischemic area (123.81 + 21.48 and 95.14 + 41.19). CONCLUSION: An intramural injection of plasmid VEGF 165 resulted in a significant increase in the number of capillaries in the peripheral AMI area. This increase may have a beneficial effect in the reduction and recovery of the ischemic area secondary to AMI.

Fatores preditivos de reversão a ritmo sinusal após intervenção na valva mitral em pacientes com fibrilação atrial crônica

Rheumatic mitral valve disease may lead to atrial fibrillation due to anatomical and functional disorders of the left atrial myocardium. After mitral valve surgery some patients in atrial fibrillation recover sinus rhythm, but the majority of them remains fibrillated. This study was undertaken with the purpose of identify, in patients operated on for mitral valve disease with atrial fibrillation, those factors that could predict a return to sinus rhythm post-operatively. The following variables were retrospectively studied: age, gender, duration of the arrhythmia pre-operatively, left atrial diameter, ejection fraction, type of valve lesion, surgical technique for correction, and previous cardiac surgery. Data was obtained from the medical history, ECG, echocardiogram and surgical note. There was no statistical significant difference between patients that returned to sinus rhythm and those that remained in atrial fibrillation, regarding age, gender, arrhythmia duration, left atrial diameter, ejection fraction, kind of technique, and previous heart surgery. Mitral regurgitation associated to left atrial less than 52 mm diameter was predictive for return to sinus rhythm (OR = 1,945; p = 0,02).The prediction of persistent post-operative atrial fibrillation may lead to changing surgical stratergies in patients with mitral valve disease. In this small series of patients, the association of mitral regurgitation and left atrial size less than 52 mm was predictive of conversion to sinus rhythm after conventional post-operative therapy.