Ivo A. Nesralla

Simple surgical isolation of pulmonary veins for treating secondary atrial fibrillation in mitral valve disease

BACKGROUND Chronic atrial fibrillation (AF) due to mitral valve disease has been successfully treated by surgery. We performed a study to evaluate the effectiveness of a surgical method of simple pulmonary vein isolation (PVI) without radiofrequency or cryoablation in the restoration of sinus rhythm in a group of patients. METHODS Fifteen patients were operated on for mitral valve disease and chronic AF. The technique consists basically of a circumferential incision excluding the pulmonary vein ostia from the left atrium. RESULTS Sinus rhythm was achieved in 92.3% of the patients at 6-month follow-up. Echocardiograms 2 months after surgery showed a mean decrease of 1.1 cm in left atrial size. Effective atrial ejection was reestablished in all patients in whom sinus rhythm was achieved (mean LA ejection fraction 41% +/- 14%). Twenty-four hour Holter recordings did not show episodes of paroxysmal atrial fibrillation in any patients. Four patients had isolated episodes of ventricular ectopic beats. Stress electrocardiograms showed mean maximal ventricular response was 64% +/- 11% and 73% +/- 9% of predicted value at 2 and 6 months, respectively. All patients had improved NYHA functional class after surgery; 74% of patients were in NYHA functional class I at 6 months compared with 13.3% preoperatively. CONCLUSIONS Pulmonary vein isolation without the use of radiofrequency or cryoablation is effective in restoring sinus rhythm in patients with chronic AF secondary to mitral valve disease. Based on simple surgical incisions, this technique is more advantageous than others requiring additional instrumentation.

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.

Effects of therapeutic angiogenesis with plasmid VEGF165 on ventricular function in a canine model of chronic myocardial infarction

OBJECTIVE Therapeutic angiogenesis is currently under investigation in ischemic heart disease. We examined the effect on left ventricular function induced by therapeutic angiogenesis by intramyocardial injection of plasmid VEGF(165), in a canine model of chronic myocardial infarction. METHODS Left thoracotomy was performed in 10 mongrel dogs, and myocardial infarction induced by ligation of the major diagonal coronary artery. At 7 postoperative (p.o.) day (pre-treatment), left ventricular ejection fraction was assessed by echocardiogram, and a second procedure was done: saline or plasmid VEGF(165) at 200 mg/mL was injected over 10 points of the ischemic areas of control or treated groups, respectively. Fourteen days later (post-treatment, day 21) a control echocardiogram was performed, the animals were sacrificed and histological examination was performed. RESULTS Ejection fraction was maintained in the treated group: 52.45 +/- 15.1% on day 7 and 48.53 +/-11.74% on day 21 (P=0.59), and tended to decrease in the control group, from 59.3 +/- 4% to 39.37 +/- 19.43% (P=0.04), although absolute values did not differ significantly between groups. Histological examination revealed a non significant increase in capillary vessels number in all areas in treated group. Paradoxically, arterioles were significantly less in number in all areas of treated dogs. CONCLUSION Intramyocardial injection of plasmid VEGF(165), in this canine model of chronic myocardial infarction, resulted in preservation of left ventricular ejection fraction, contrary to the control group where left ventricular ejection fraction showed continuous decline during the experiment. Histological examination, however, was unable to explain completely these results.

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.

Cardiac Tamponade due to Chylopericardium after Cardiac Surgery

Chylopericardium as an isolated complication after open-heart surgery is a rare event. We present here a case of postoperative chylopericardium with cardiac tamponade and comment on the clinical course and treatment.

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.

Implante valvular aórtico percutâneo: experiência inicial do Sul do Brasil

BACKGROUND: Severe aortic stenosis is a prevalent disease with high rates of morbidity and mortality. The classic approach to its treatment is through heart valve replacement surgery. However, elderly patients and others with different comorbidities present high surgical risk. The percutaneous aortic valve implantation through a retrograde approach has emerged as a feasible and effective alternative treatment for this issue. We describe the first series of cases treated with this new approach in the South of Brazil. METHODS: Series of three cases describing the procedure and immediate results of CoreValve device implantation. This device consists in a bioprosthesis with three porcine leafs mounted and sutured in a self-expandable nitinol stent introduced through the femoral or iliac artery. RESULTS: Three female patients aged 81, 85 and 90 years with a logistic EuroSCORE varying from 20% to 36% were successfully submitted to the implantation of this device. A significant reduction in all gradients between the left ventricle and the aorta was observed. There were no reports of major cardiovascular complications, although in two patients the implantation of a permanent pacemaker was needed due to an atrioventricular conduction disorder. All patients were discharged asymptomatic and were kept in a long-term clinical follow-up evaluation program. CONCLUSION: The initial short-term experience with the percutaneous retrograde aortic valve implantation in the south of Brazil was feasible and safe. Additional studies and long-term follow-up are still necessary in order to define the precise role and adequate indications for this new and very promising technique.