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/

Terapia gênica com fator de crescimento endotelial vascular 165 para pacientes com angina refratária: mobilização de células progenitoras endoteliais / VEGF 165 gene therapy for patients with refractory angina: mobilization of endothelial progenitor cells

FUNDAMENTO: O fator de crescimento endotelial vascular (VEGF - vascular endothelial growth factor) induz a mobilização de células progenitoras endoteliais (CPEs) com capacidade de proliferação e diferenciação em células endoteliais, contribuindo, dessa forma, para o processo angiogênico. OBJETIVO: Buscamos avaliar o comportamento de CPEs em pacientes com doença cardíaca isquêmica e angina refratária que receberam injeções intramiocardicas de 2000 µg de VEGF165 como terapia única. MÉTODOS: O estudo foi uma subanálise de um ensaio clínico. Pacientes com doença cardíaca isquêmica avançada e angina refratária foram avaliados para inclusão no estudo. Os critérios de inclusão foram: sinais e sintomas de angina e/ou insuficiência cardíaca apesar de tratamento medicamentoso máximo e área de isquemia miocárdica de, no mínimo, 5% conforme avaliado por uma tomografia computadorizada por emissão de fóton único (TCEFU). Os critérios de exclusão foram: idade > 65 anos, fração de ejeção do ventrículo esquerdo < 25% e cancer diagnosticado. Os pacientes cujos níveis de CPE foram avaliados foram incluídos. A intervenção consistiu na administração de 2000 µg de VEGF 165 de plasmídeo injetado no miocárdio isquêmico. A frequência de células CD34+/KDR+ foi analisada por citometria de fluxo antes e 3, 9, e 27 dias após a intervenção. RESULTADOS: Um total de 9 pacientes foram incluídos, 8 homens, média de idade de 59,4 anos, fração de ejeção ventricular esquerda de 59,3%, e classe de angina predominante III. Observou-se um aumento significativo dos níveis de CPEs no terceiro dia após a intervenção. Todavia, 9 e 27 dias após a intervenção, os níveis de CPEs foram similares aos basais. CONCLUSÃO: Identificamos uma mobilização transitória de CPE, com pico no terceiro dia após a intervenção com VEGF 165 em pacientes com angina refratária. Todavia, os níveis de CPEs apresentaram-se semelhantes aos basais 9 e 27 dias após a intervenção.

BACKGROUND: Vascular endothelial growth factor (VEGF) induces mobilization of endothelial progenitor cells (EPCs) with the capacity for proliferation and differentiation into mature endothelial cells, thus contributing to the angiogenic process. OBJECTIVE: We sought to assess the behavior of EPCs in patients with ischemic heart disease and refractory angina who received an intramyocardial injections of 2000 µg of VEGF 165 as the sole therapy. METHODS: The study was a subanalysis of a clinical trial. Patients with advanced ischemic heart disease and refractory angina were assessed for eligibility. Inclusion criteria were as follows: signs and symptoms of angina and/or heart failure despite maximum medical treatment and a myocardial ischemic area of at least 5% as assessed by single-photon emission computed tomography (SPECT). Exclusion criteria were as follows: age > 65 years, left ventricular ejection fraction < 25%, and a diagnosis of cancer. Patients whose EPC levels were assessed were included. The intervention was 2000 µg of VEGF 165 plasmid injected into the ischemic myocardium. The frequency of CD34+/KDR+ cells was analyzed by flow cytometry before and 3, 9, and 27 days after the intervention. RESULTS: A total of 9 patients were included, 8 males, mean age 59.4 years, mean left ventricular ejection fraction of 59.3% and predominant class III angina. The number of EPCs on day 3 was significantly higher than that at baseline (p = 0.03); however, that on days 9 and 27 was comparable to that at baseline. CONCLUSION: We identified a transient mobilization of EPCs, which peaked on the 3th day after VEGF 165 gene therapy in patients with refractory angina and returned to near baseline levels on days 9 and 27.

VEGF 165 gene therapy for patients with refractory angina: mobilization of endothelial progenitor cells.

BACKGROUND: Vascular endothelial growth factor (VEGF) induces mobilization of endothelial progenitor cells (EPCs) with the capacity for proliferation and differentiation into mature endothelial cells, thus contributing to the angiogenic process. OBJECTIVE: We sought to assess the behavior of EPCs in patients with ischemic heart disease and refractory angina who received an intramyocardial injections of 2000 µg of VEGF 165 as the sole therapy. METHODS: The study was a subanalysis of a clinical trial. Patients with advanced ischemic heart disease and refractory angina were assessed for eligibility. Inclusion criteria were as follows: signs and symptoms of angina and/or heart failure despite maximum medical treatment and a myocardial ischemic area of at least 5% as assessed by single-photon emission computed tomography (SPECT). Exclusion criteria were as follows: age > 65 years, left ventricular ejection fraction < 25%, and a diagnosis of cancer. Patients whose EPC levels were assessed were included. The intervention was 2000 µg of VEGF 165 plasmid injected into the ischemic myocardium. The frequency of CD34+/KDR+ cells was analyzed by flow cytometry before and 3, 9, and 27 days after the intervention. RESULTS: A total of 9 patients were included, 8 males, mean age 59.4 years, mean left ventricular ejection fraction of 59.3% and predominant class III angina. The number of EPCs on day 3 was significantly higher than that at baseline (p = 0.03); however, that on days 9 and 27 was comparable to that at baseline. CONCLUSION: We identified a transient mobilization of EPCs, which peaked on the 3th day after VEGF 165 gene therapy in patients with refractory angina and returned to near baseline levels on days 9 and 27.

Results of simplified single-patch repair for complete atrioventricular septal defect.

BACKGROUND: Since Wilcox's description of the simplified single-patch technique for atrioventricular septal defect (AVSD) repair in 1997, several studies have compared that technique with the two-patch technique. OBJECTIVE: To report the mid- and long-term results of the simplified single-patch technique for complete AVSD repair. METHODS: Retrospective study of 16 consecutive cases between January 2001 and December 2011. The patients' mean age was 18.31 ± 34.19 months (2 months - 11 years), and their mean weight, 7.80 ± 6.12 kg (3.77 - 25.0 kg). Six patients were males and 14 had Down syndrome. Mean follow-up duration was 54.97 ± 47.79 months. RESULTS: Mean cardiopulmonary bypass time was 74.63 ± 18.48 min (49 - 112 min), and mean aortic cross-clamp time, 46.44 ± 11.89 min (34 - 67 min). Two patients died during hospitalization (12.5%), both of cardiovascular causes. Three patients underwent reoperation due to left atrioventricular (AV) valve regurgitation, and two had third-degree VA block, requiring permanent pacemaker implantation. No patient had left ventricular outflow tract obstruction. The 14 surviving patients remain asymptomatic, ten of whom with mild left VA valve regurgitation (71.42%). CONCLUSION: The simplified single-patch technique for complete AVSD repair proved to be feasible, providing adequate correction of the defects and favorable clinical and echocardiographic outcome in the mean 57.97-month follow-up.

Resultados da correção simplificada com enxerto único no defeito septal atrioventricular completo / Results of simplified single-patch repair for complete atrioventricular septal defect

FUNDAMENTO: Desde que Wilcox, em 1997, descreveu uma forma simplificada de correção do Defeito Septal Atrioventricular (DSAV) com enxerto único, diversos estudos têm sido realizados comparando-a à técnica com duplo enxerto. OBJETIVO: Relatar os resultados em médio e longo prazos da correção de DSAV completo pela técnica simplificada de enxerto único. MÉTODOS: Estudo retrospectivo de 16 casos consecutivos arrolados entre janeiro de 2001 e dezembro de 2011. A idade média foi 18,31 ± 34,19 meses (2 meses - 11 anos) e o peso 7,80 ± 6,12 Kg (3,77 - 25,0 Kg); 6 pacientes eram do sexo masculino e 14 eram portadores de Síndrome de Down. O tempo de seguimento médio foi de 54,97 ± 47,79 meses. RESULTADOS: O tempo médio de circulação extracorpórea foi 74,63 ± 18,48 min (49 - 112 min) e o de pinçamento aórtico, de 46,44 ± 11,89 min (34 - 67 min). Foram observados dois óbitos hospitalares (12,5%), ambos por causa cardiovascular. Três pacientes foram reoperados por regurgitação da valva atrioventricular (VA) esquerda e dois apresentaram bloqueio atrioventricular (BAV) completo com necessidade de implante de marca-passo definitivo. Não houve nenhum caso de obstrução da via de saída do ventrículo esquerdo. Os 14 pacientes sobreviventes permanecem assintomáticos, 10 deles com insuficiência da valva VA esquerda leve (71,42%). CONCLUSÃO: A técnica simplificada com enxerto único para correção de DSAV completo mostrou-se factível, associada à correção adequada dos defeitos e à favorável evolução clínica e ecocardiográfica nos 57,97 meses de seguimento médio avaliados.

BACKGROUND: Since Wilcox's description of the simplified single-patch technique for atrioventricular septal defect (AVSD) repair in 1997, several studies have compared that technique with the two-patch technique. OBJECTIVE: To report the mid- and long-term results of the simplified single-patch technique for complete AVSD repair. METHODS: Retrospective study of 16 consecutive cases between January 2001 and December 2011. The patients' mean age was 18.31 ± 34.19 months (2 months - 11 years), and their mean weight, 7.80 ± 6.12 kg (3.77 - 25.0 kg). Six patients were males and 14 had Down syndrome. Mean follow-up duration was 54.97 ± 47.79 months. RESULTS: Mean cardiopulmonary bypass time was 74.63 ± 18.48 min (49 - 112 min), and mean aortic cross-clamp time, 46.44 ± 11.89 min (34 - 67 min). Two patients died during hospitalization (12.5%), both of cardiovascular causes. Three patients underwent reoperation due to left atrioventricular (AV) valve regurgitation, and two had third-degree VA block, requiring permanent pacemaker implantation. No patient had left ventricular outflow tract obstruction. The 14 surviving patients remain asymptomatic, ten of whom with mild left VA valve regurgitation (71.42%). CONCLUSION: The simplified single-patch technique for complete AVSD repair proved to be feasible, providing adequate correction of the defects and favorable clinical and echocardiographic outcome in the mean 57.97-month follow-up.

Fatores de risco hospitalar para pacientes submetidos à substituição valvar com a bioprótese porcina em instituição universitária / Risk factors for hospital mortality in valve replacement with porcine bioprosthesis at an universitary institution

OBJETIVO: Identificar fatores de risco hospitalar em pacientes submetidos ao implante de bioprótese porcina no Instituto de Cardiologia do Rio Grande do Sul. MÉTODOS: Estudo retrospectivo, com informações de prontuário, de 808 pacientes submetidos ao implante de pelo menos uma bioprótese porcina St. Jude Medical Biocor, no período entre 1994 e 2009. Foi analisada a relação entre mortalidade hospitalar e características clínicas e demográficas definidas em estudos reconhecidos, visando identificar fatores de risco. Foram utilizados testes qui-quadrado, t de Student e regressão logística uni e multivariável (P<0,05). RESULTADOS: Ocorreram 80 (9,9%) óbitos hospitalares. Fatores de risco identificados na regressão logística univariável foram: plastia tricúspide (odds ratio 6,11); lesão mitral (OR 3,98); fração de ejeção de ventrículo esquerdo < 30% (OR 3,82); diabete melito (OR 2,55); fibrilação atrial (OR 2,32); hipertensão pulmonar (OR 2,30); creatinina > 1,4 mg/dL (OR 2,28); cirurgia cardíaca prévia (OR 2,17); hipertensão arterial sistêmica (OR 1,93); classe funcional III e IV (OR 1,92); revascularização miocárdica (OR 1,81); idade > 70 anos (OR 1,80); insuficiência cardíaca congestiva (OR 1,73); e sexo feminino (OR 1,68). Pela regressão logística multivariável, para fatores independentes, identificados: lesão mitral (OR 5,29); plastia tricúspide (OR 3,07); diabete melito (OR 2,72); idade > 70 anos (OR 2,62); revascularização miocárdica (OR 2,43); cirurgia cardíaca prévia (OR 1,82); e hipertensão arterial sistêmica (OR 1,79). CONCLUSÕES: A mortalidade observada nesta casuística é compatível com literatura. Fatores de risco preponderantes são reconhecidos e devem motivar programas específicos de neutralização.

OBJECTIVE: Study designed to identify characteristics of patients related to increased hospital mortality after valve replacement, assumed as risk factors. METHODS: Retrospective study including 808 patients submitted to the implant of St. Jude Biocor porcine bioprosthesis between 1994 and 2009 at Instituto de Cardiologia do Rio Grande do Sul. Primary outcome was hospital death and hospital mortality was related to demographic and surgical characteristics. Statistics include t-test, qui-square test and logistical regression analysis. RESULTS: There were 80 (9.9%) hospital deaths. Risk factors identified with univariable logistical analysis (and respective odds-ratio) were: tricuspid surgery (OR 6.11); mitral valve replacement (OR 3.98); left ventricular ejection fraction < 30% (OR 3.82); diabetes mellitus (OR 2.55); atrial fibrillation (OR 2.32); pulmonary arterial hypertension (OR 2.30); serum creatinine > 1,4 mg/dL (OR 2.28); previous cardiac surgery (OR 2.17); systemic arterial hypertension (OR 1.93); functional class III e IV (OR 1.92); coronary bypass (OR 1.81); age > 70 years-old (OR 1.80); congestive heart failure (OR 1.73); e female gender (OR 1.68). Multivariable logistic regression for independent factors identified preponderant risk factors mitral valve replacement (OR 5,29); tricuspid surgery (OR 3.07); diabetes mellitus (OR 2.72); age > 70 years-old (OR 2.62); coronary bypass (OR 2.43); previous cardiac surgery (OR 1.82); e systemic arterial hypertension (OR 1.79). CONCLUSIONS: Mortality rate is within values found in literature. Identification of risk factors could contribute to changes in surgical indication and medical management in order to reduce hospital mortality.

Does diabetes mellitus increase immediate surgical risk in octogenarian patients submitted to coronary artery bypass graft surgery? / Diabetes mellitus aumenta risco cirúrgico imediato em pacientes octogenários submetidos à cirurgia de revascularização miocárdica?

INTRODUCTION: Diabetes is a well known risk factor for early and late adverse outcomes in patients undergoing coronary artery bypass graft surgery (CABG); however, few studies have investigated the impact of this risk factor in the group of older patients, especially octogenarians. OBJECTIVES: To compare in-hospital mortality and morbidity of diabetic and nondiabetic patients aged > 80 years submitted to CABG. METHODS: A total of 140 consecutive cases were studied, of whom 37 (26.4%) were diabetics, in a retrospective cross-sectional study, that included all patients aged > 80 years submitted to isolated/associated CABG. The patients' mean age was 82.5 ± 2.2 years and 55.7% were males. RESULTS: The hospital mortality rate did not significantly differ in multivariate analysis: 16.2% diabetic x 13.6% nondiabetic (P = 0.554), as well as morbidity: 43.2% x 37.9%, respectively (P = 0.533). Regarding to operative morbidity, the occurrence of stroke was significantly higher in diabetic patients in the univariate analysis (10.8% x 1.9%, P = 0.042). In multivariate analysis, however, the incidence of stroke was not associated with the presence of diabetes (P = 0.085), but it was associated with atrial fibrillation (P = 0.044). There was no significant difference related to other complications. CONCLUSION: In this small consecutive retrospectively analyzed series, there was no significant increase in hospital mortality and morbidity related to diabetes for CABG in octogenarian patients. The impact of the results of this study is limited by the sample size and might be confirmed by future randomized clinical trials.

INTRODUÇÃO: O diabetes é um fator de risco conhecido para eventos adversos precoces e tardios em pacientes submetidos à cirurgia de revascularização miocárdica (CRM); entretanto, poucos estudos investigaram sua influência no grupo de pacientes mais idosos, especialmente nos octogenários. OBJETIVOS: Comparar a mortalidade e a morbidade hospitalar de pacientes com idade > 80 anos diabéticos e não-diabéticos submetidos à CRM. MÉTODOS: Foram estudados 140 casos consecutivos, sendo 37 (26,4%) diabéticos, em um estudo transversal retrospectivo incluindo todos os pacientes com idade > 80 anos submetidos à CRM isolada/associada. A idade média dos pacientes foi de 82,5 ± 2,2 anos e 55,7% eram do sexo masculino. RESULTADOS: A taxa de mortalidade hospitalar não diferiu de maneira significativa na análise multivariada entre os grupos, 16,2% diabéticos x 13,6% não-diabéticos (P=0,554), assim como a morbidade pós-operatória, 43,2 x 37,9%, respectivamente (P=0,533). Em relação à morbidade, a ocorrência de acidente vascular cerebral foi significativamente maior em pacientes diabéticos na análise univariada (10,8% x 1,9%; P = 0,042). Na análise multivariada, no entanto, a incidência dessa complicação não foi associada com a presença de diabetes (P=0,085), mas com a presença de fibrilação atrial (P=0,044). Não se observou nenhuma diferença significativa em relação às outras complicações. CONCLUSÃO: Nessa pequena série de casos retrospectiva, não houve um aumento significativo da morbimortalidade hospitalar no grupo de pacientes octogenários diabéticos. O impacto dos resultados desta série é limitado pelo tamanho amostral e poderá ser confirmado por futuros ensaios clínicos randomizados.

Risk factors for hospital mortality in valve replacement with porcine bioprosthesis at an universitary institution.

OBJECTIVE: Study designed to identify characteristics of patients related to increased hospital mortality after valve replacement, assumed as risk factors. METHODS: Retrospective study including 808 patients submitted to the implant of St. Jude Biocor porcine bioprosthesis between 1994 and 2009 at Instituto de Cardiologia do Rio Grande do Sul. Primary outcome was hospital death and hospital mortality was related to demographic and surgical characteristics. Statistics include t-test, qui-square test and logistical regression analysis. RESULTS: There were 80 (9.9%) hospital deaths. Risk factors identified with univariable logistical analysis (and respective odds-ratio) were: tricuspid surgery (OR 6.11); mitral valve replacement (OR 3.98); left ventricular ejection fraction < 30% (OR 3.82); diabetes mellitus (OR 2.55); atrial fibrillation (OR 2.32); pulmonary arterial hypertension (OR 2.30); serum creatinine > 1,4 mg/dL (OR 2.28); previous cardiac surgery (OR 2.17); systemic arterial hypertension (OR 1.93); functional class III e IV (OR 1.92); coronary bypass (OR 1.81); age > 70 years-old (OR 1.80); congestive heart failure (OR 1.73); e female gender (OR 1.68). Multivariable logistic regression for independent factors identified preponderant risk factors mitral valve replacement (OR 5,29); tricuspid surgery (OR 3.07); diabetes mellitus (OR 2.72); age > 70 years-old (OR 2.62); coronary bypass (OR 2.43); previous cardiac surgery (OR 1.82); e systemic arterial hypertension (OR 1.79). CONCLUSIONS: Mortality rate is within values found in literature. Identification of risk factors could contribute to changes in surgical indication and medical management in order to reduce hospital mortality.

Does diabetes mellitus increase immediate surgical risk in octogenarian patients submitted to coronary artery bypass graft surgery?

INTRODUCTION: Diabetes is a well known risk factor for early and late adverse outcomes in patients undergoing coronary artery bypass graft surgery (CABG); however, few studies have investigated the impact of this risk factor in the group of older patients, especially octogenarians. OBJECTIVES: To compare in-hospital mortality and morbidity of diabetic and nondiabetic patients aged > 80 years submitted to CABG. METHODS: A total of 140 consecutive cases were studied, of whom 37 (26.4%) were diabetics, in a retrospective cross-sectional study, that included all patients aged > 80 years submitted to isolated/associated CABG. The patients' mean age was 82.5 ± 2.2 years and 55.7% were males. RESULTS: The hospital mortality rate did not significantly differ in multivariate analysis: 16.2% diabetic x 13.6% nondiabetic (P = 0.554), as well as morbidity: 43.2% x 37.9%, respectively (P = 0.533). Regarding to operative morbidity, the occurrence of stroke was significantly higher in diabetic patients in the univariate analysis (10.8% x 1.9%, P = 0.042). In multivariate analysis, however, the incidence of stroke was not associated with the presence of diabetes (P = 0.085), but it was associated with atrial fibrillation (P = 0.044). There was no significant difference related to other complications. CONCLUSION: In this small consecutive retrospectively analyzed series, there was no significant increase in hospital mortality and morbidity related to diabetes for CABG in octogenarian patients. The impact of the results of this study is limited by the sample size and might be confirmed by future randomized clinical trials.

Terapia gênica para cardiopatia isquêmica: revisão de ensaios clínicos / Gene therapy for ischemic heart disease: review of clinical trials

Cardiopatia isquêmica grave com angina refratária a formas convencionais de tratamento apresenta-se em uma crescente incidência. Para tratar angina refratária, terapias alternativas na tentativa de redução da isquemia miocárdica e alívio de sintomas têm sido estudadas. Neste contexto, a terapia gênica representa uma opção, pela possibilidade de induzir angiogênese, estabelecer circulação colateral e reperfundir miocárdio isquêmico. Diversos ensaios clínicos têm sido conduzidos e, com exceção de casos isolados e específicos de efeitos adversos, há indicação de segurança, viabilidade e potencial eficácia da terapia. O benefício clínico não está bem definido. Neste artigo, revisamos os ensaios clínicos que utilizaram terapia gênica para tratamento de pacientes cardiopatas isquêmicos. A abordagem inclui: (1) isquemia miocárdica e angiogênese, sobre os aspectos fisiopatológicos envolvidos; (2) fatores de crescimento, tratando sobre aspectos específicos e justificando a utilização em pacientes cardiopatas isquêmicos sem opções pela terapêutica convencional; (3) ensaios clínicos controlados, onde é apresentado um resumo dos principais estudos envolvendo terapia gênica para tratamento da cardiopatia isquêmica grave; (4) nossa experiência, especialmente sobre resultados preliminares do primeiro ensaio clínico de terapia gênica do Brasil e (5) perspectivas.

Severe ischemic heart disease with refractory angina, occurs in increasing incidence. Alternative forms of treatment, in an attempt to reduce myocardial ischemia and relief of symptoms has been studied. In this context, gene therapy is an option, for the possibility of inducing angiogenesis, establish collateral circulation and reperfuse ischemic myocardium. Several clinical trials have been conducted and, except for specific cases of adverse effects, there is indication of safety, feasibility and potential effectiveness of therapy. The clinical benefit, however, is not yet well established. In this article we review the clinical trials of gene therapy for patients with ischemic heart disease. The approach includes: (1) myocardial ischemia and angiogenesis on the pathophysiological aspects involved, (2) growth factors, dealing with specific aspects and justifying the use in cardiac patients with no option for conventional therapy, (3) controlled clinical trials, where a summary of the main studies involving gene therapy for severe ischemic heart disease is presented, (4) our experience, especially on preliminary results of the first gene therapy clinical trial in Brazil and (5) future prospects.

Long-term survival of octogenarian patients submitted to isolated coronary artery bypass graft surgery.

INTRODUCTION: An increasing number of octogenarian patients is undergoing coronary artery bypass graft surgery (CABG). The short-term results of this procedure have been broadly studied, but there are few national reports on long-term outcomes. OBJECTIVES: To describe hospital mortality and long-term survival of patients aged > 80 years undergoing isolated CABG. METHODS: Retrospective cohort study with 142 consecutive patients aged > 80 years undergoing isolated CABG in the period between January/1996 and December/2007 in a Brazilian reference center. Mean age (± SD) was 82.3 ± 2.1 years, and 56.3% were male. The prevalence of hypertension was 73.2%, of previous myocardial infarction 30.3%, of diabetes 26.8%, and of renal dysfunction (creatinine ³ 2.0 mg/ml) was 4.9%. The median follow-up was 4.0 years, with a loss of 11.6% of patients. Survival analysis was performed by the Kaplan-Meier method. RESULTS: Overall hospital mortality was 14.8% (95% CI: 8.8 to 20.8), with a reduction of this rate during the study period (1996-1999: 25.9%, 2000-2003: 15.8%, and 2004-2007: 8.6%). Mean survival was 6.5 years (95% CI: 5.5 to 7.5), and the survival rate at 1, 3 and 5 years was 79.4, 73.4 and 65.2%, respectively. CONCLUSION: Results are in agreement with international reports. Mean survival was 6.5 years and the survival rate at 5 years was 65.2%.

Sobrevida em longo prazo de octogenários submetidos à cirurgia de revascularização miocárdica isolada / Long-term survival of octogenarian patients submitted to isolated coronary artery bypass graft surgery

INTRODUÇÃO: Um crescente número de pacientes octogenários tem sido submetido à cirurgia de revascularização miocárdica (CRM). Os resultados em curto prazo desse procedimento têm sido amplamente estudados, mas há poucos relatos nacionais até o presente momento sobre os seus desfechos em longo prazo. OBJETIVOS: Descrever a mortalidade hospitalar e a sobrevida em longo prazo de pacientes com idade 80 anos submetidos à CRM isolada. MÉTODOS: Estudo de coorte retrospectivo com 142 pacientes consecutivos de idade 80 anos submetidos à CRM isolada no período de janeiro/1996 a dezembro/2007. A idade média (±dp) foi de 82,3±2,1 anos e 56,3% eram masculinos. A prevalência de hipertensão arterial sistêmica foi de 73,2%, infarto agudo do miocárdio prévio 30,3%, diabetes melito 26,8% e disfunção renal (creatinina ³ 2,0mg/ml) 4,9%. A mediana do seguimento foi de 4,0 anos, havendo perda de 11,6% dos pacientes. A análise da sobrevida foi feita pela curva de Kaplan-Meier. RESULTADOS: A mortalidade hospitalar geral foi de 14,8% (IC95%: 8,8-20,8), observando-se uma redução desse percentual ao longo do período estudado (1996-1999: 25,9%, 2000-2003: 15,8% e 2004-2007: 8,6%). A média de sobrevida foi de 6,5 anos (IC95%: 5,5-7,5), sendo a taxa de sobrevida em 1, 3 e 5 anos de 83,3, 79,5 e 77,3%, respectivamente. CONCLUSÕES: A média de sobrevida foi de 6,5 anos, sendo a taxa em 5 anos de 77,3%, dados condizentes com a literatura internacional.

INTRODUCTION: An increasing number of octogenarian patients is undergoing coronary artery bypass graft surgery (CABG). The short-term results of this procedure have been broadly studied, but there are few national reports on long-term outcomes. OBJECTIVES: To describe hospital mortality and long-term survival of patients aged > 80 years undergoing isolated CABG. METHODS: Retrospective cohort study with 142 consecutive patients aged > 80 years undergoing isolated CABG in the period between January/1996 and December/2007 in a Brazilian reference center. Mean age (± SD) was 82.3 ± 2.1 years, and 56.3% were male. The prevalence of hypertension was 73.2%, of previous myocardial infarction 30.3%, of diabetes 26.8%, and of renal dysfunction (creatinine ³ 2.0 mg/ml) was 4.9%. The median follow-up was 4.0 years, with a loss of 11.6% of patients. Survival analysis was performed by the Kaplan-Meier method. RESULTS: Overall hospital mortality was 14.8% (95% CI: 8.8 to 20.8), with a reduction of this rate during the study period (1996-1999: 25.9%, 2000-2003: 15.8%, and 2004-2007: 8.6%). Mean survival was 6.5 years (95% CI: 5.5 to 7.5), and the survival rate at 1, 3 and 5 years was 79.4, 73.4 and 65.2%, respectively. CONCLUSION: Results are in agreement with international reports. Mean survival was 6.5 years and the survival rate at 5 years was 65.2%.

Gene therapy for ischemic heart disease: review of clinical trials.

Severe ischemic heart disease with refractory angina, occurs in increasing incidence. Alternative forms of treatment, in an attempt to reduce myocardial ischemia and relief of symptoms has been studied. In this context, gene therapy is an option, for the possibility of inducing angiogenesis, establish collateral circulation and reperfuse ischemic myocardium. Several clinical trials have been conducted and, except for specific cases of adverse effects, there is indication of safety, feasibility and potential effectiveness of therapy. The clinical benefit, however, is not yet well established. In this article we review the clinical trials of gene therapy for patients with ischemic heart disease. The approach includes: (1) myocardial ischemia and angiogenesis on the pathophysiological aspects involved, (2) growth factors, dealing with specific aspects and justifying the use in cardiac patients with no option for conventional therapy, (3) controlled clinical trials, where a summary of the main studies involving gene therapy for severe ischemic heart disease is presented, (4) our experience, especially on preliminary results of the first gene therapy clinical trial in Brazil and (5) future prospects.

Morbimortalidade em octogenários submetidos à cirurgia de revascularização miocárdica / Morbimortality in octogenarian patients submitted to coronary artery bypass graft surgery

FUNDAMENTO: O progressivo aumento da longevidade da população tem levado cada vez mais pacientes octogenários a necessitarem de cirurgia de revascularização miocárdica (CRM), sendo necessário conhecer os riscos e benefícios desse procedimento nessa faixa etária. OBJETIVO: Descrever a morbimortalidade hospitalar de pacientes com idade igual ou superior a 80 anos submetidos à CRM e identificar variáveis que se constituem em seus preditores. MÉTODOS: Foram estudados 140 casos consecutivos entre janeiro de 2002 e dezembro de 2007. Os pacientes possuíam em média 82,5 ± 2,2 anos (80-89), e 55,7 por cento eram do sexo masculino. Na amostra, 72,9 por cento tinham hipertensão arterial, 26,4 por cento diabete, 65,7 por cento lesão grave em três ou mais vasos e 28,6 por cento em tronco da coronária esquerda. Cirurgia associada esteve presente em 35,7 por cento dos pacientes, sendo a valvar aórtica em 26,4 por cento e a mitral em 5,6 por cento. RESULTADOS: A mortalidade foi de 14,3 por cento (CRM isolada 10,0 por cento x 22,0 por cento associada; p = 0,091) e a morbidade de 37,9 por cento (CRM isolada 34,4 por cento x 44,0 por cento associada; p = 0,35). Complicações mais frequentes: baixo débito cardíaco (27,9 por cento), disfunção renal (10,0 por cento) e suporte ventilatório prolongado (9,6 por cento). Na análise bivariada, os maiores preditores de mortalidade foram sepse (RR 10,2 IC 95 por cento: 6,10-17,7), CRM prévia (RR 8,06 IC 95 por cento: 5,16-12,6), baixo débito cardíaco pós-operatório (RR 7,77 IC 95 por cento: 3,03-19,9) e disfunção renal pós-operatória (RR 7,36 IC 95 por cento: 3,71-14,6). Quanto à morbidade, foram preditores tempo de circulação extracorpórea >120 min. (RR: 2,34 IC 95 por cento: 1,62-3,38) e de isquemia > 90 min. (RR: 2,29 IC 95 por cento: 1,56-3,37). CONCLUSÃO: A CRM em octogenários está relacionada a uma morbimortalidade maior do que nos pacientes mais jovens, o que, entretanto, não impede a intervenção se houver indicação...

BACKGROUND: Given the progressive increase in longevity and the need of an increasingly elderly population to undergo myocardial revascularization surgery (MRS), it becomes necessary to know its risks and benefits. OBJECTIVE: To evaluate the in-hospital morbimortality of patients aged 80 and older submitted to MRS and identify its predictor variables. METHODS: A total of 140 consecutive cases were studied between January 2002 and December 2007. The patients' mean age was 82.5 ± 2.2 years (range: 80-89) and 55.7 percent were males. In the sample,72.9 percent had arterial hypertension, 26.4 percent had diabetes, 65.7 percent presented severe lesion in three or more vessels and 28.6 percent presented a severe lesion in the left coronary trunk. An associated surgery was present in 35.7 percent of the cases, with aortic valve in 26.4 percent and mitral valve in 5.6 percent. RESULTS: The mortality rate was 14.3 percent (isolated MRS 10.0 percent vs 22.0 percent with associated procedure; p = 0.091) and the morbidity was 37.9 percent (isolated MRS 34.4 percent vs 44.0 percent with associated procedure; p = 0.35). The most frequent complications were low cardiac output (27.9 percent), renal dysfunction (10.0 percent) and prolonged ventilatory support (9.6 percent). At the bivariate analysis, the most important mortality predictors were sepsis (RR 10.2; 95 percentCI: 6.10-17.7), previous MRS (RR 8.06; 95 percentCI: 5.16-12.6), postoperative low cardiac output (RR 7.77; 95 percentCI: 3.03-19.9) and postoperative renal dysfunction (RR 7.36; 95 percentCI: 3.71-14.6). The morbidity predictors were extracorporeal circulation time > 120 min. (RR: 2.34; 95 percentCI: 1.62-3.38) and time of ischemia > 90 min. (RR: 2.29 95 percentCI: 1.56-3.37). CONCLUSION: The MRS in octogenarians is associated with a higher morbimortality when compared to younger patients, which, however, does not prevent the procedure if the indication is justified by clinical condition.

Comparison of surgical cut and sew versus radiofrequency pulmonary veins isolation for chronic permanent atrial fibrillation: a randomized study.

BACKGROUND: Surgical pulmonary veins isolation (PVI) is done to restore sinus rhythm (SR) in patients with chronic permanent atrial fibrillation (CPAF) and mitral valve disease. Here we compare the efficacy of electrical block lines performed with radiofrequency (RF) compared with conventional surgery. METHODS: Randomized trial of 22 patients with CPAF and indication for mitral valve surgery. Ten patients underwent conventional surgery (SURG) and 12 RF. To prove the efficacy of the blockage lines, epicardial pacemaker wires were placed in the isolated pulmonary veins region (IPVR) and right atria (RA). RESULTS: There were no differences in the baseline data among the groups. All patients remained in SR during the immediate postoperative period. Block lines were tested in patients who remained in SR during the following days (eight in SURG and nine in RF). The median value of thresholds to conduct the stimulus of IPVR for the RA was 18 mA in SURG and 3 mA in RF (P < 0.022). Eight SURG patients and seven RF patients (P < 0.38) remained in SR at hospital discharge. Eleven RF patients and one SURG required amiodarone to maintain SR (P < 0.001). The incidence of recurrent atrial fibrillation (AF) in the follow-up was 10.7/100 patients/year in the SURG group versus 73.1/100 patients/year in the RF group (P = 0.009). CONCLUSIONS: PVI by SURG formed more effective block lines than RF. SR at hospital discharge was similar among the groups, but more amiodarone was used in RF. During follow-up, incidence of recurrent AF was higher in the RF group.

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 × 10(7) 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.

Morbimortality in octogenarian patients submitted to coronary artery bypass graft surgery.

BACKGROUND: Given the progressive increase in longevity and the need of an increasingly elderly population to undergo myocardial revascularization surgery (MRS), it becomes necessary to know its risks and benefits. OBJECTIVE: To evaluate the in-hospital morbimortality of patients aged 80 and older submitted to MRS and identify its predictor variables. METHODS: A total of 140 consecutive cases were studied between January 2002 and December 2007. The patients' mean age was 82.5 +/- 2.2 years (range: 80-89) and 55.7% were males. In the sample,72.9% had arterial hypertension, 26.4% had diabetes, 65.7% presented severe lesion in three or more vessels and 28.6% presented a severe lesion in the left coronary trunk. An associated surgery was present in 35.7% of the cases, with aortic valve in 26.4% and mitral valve in 5.6%. RESULTS: The mortality rate was 14.3% (isolated MRS 10.0% vs 22.0% with associated procedure; p = 0.091) and the morbidity was 37.9% (isolated MRS 34.4% vs 44.0% with associated procedure; p = 0.35). The most frequent complications were low cardiac output (27.9%), renal dysfunction (10.0%) and prolonged ventilatory support (9.6%). At the bivariate analysis, the most important mortality predictors were sepsis (RR 10.2; 95%CI: 6.10-17.7), previous MRS (RR 8.06; 95%CI: 5.16-12.6), postoperative low cardiac output (RR 7.77; 95%CI: 3.03-19.9) and postoperative renal dysfunction (RR 7.36; 95%CI: 3.71-14.6). The morbidity predictors were extracorporeal circulation time > 120 min. (RR: 2.34; 95%CI: 1.62-3.38) and time of ischemia > 90 min. (RR: 2.29 95%CI: 1.56-3.37). CONCLUSION: The MRS in octogenarians is associated with a higher morbimortality when compared to younger patients, which, however, does not prevent the procedure if the indication is justified by clinical condition.

Morbimortalidade em pacientes acima de 75 anos submetidos à cirurgia por estenose valvar aórtica / Morbidity and mortality in patients aged over 75 years undergoing surgery for aortic valve replacement

FUNDAMENTO: A maior longevidade observada atualmente ocasionou aumento do número de idosos que necessitam de intervenções cirúrgicas. A estenose aórtica é uma condição frequente nessa faixa etária. OBJETIVO: Avaliar morbidade e mortalidade hospitalar em pessoas de 75 anos ou mais, que tenham sido submetidas à cirurgia de valvuloplastia, ou de troca valvar por estenose aórtica isolada ou associada a outras lesões. MÉTODOS: Foram estudados 230 casos consecutivos entre jan/2002-dez/2007. Os pacientes tinham 79,5 ± 3,7 anos (75 - 94), sendo que 53,9 por cento eram homens. Na amostra, 68,7 por cento tinham hipertensão arterial, 17,9 por cento tinham fibrilação atrial, 15,9 por cento apresentaram obesidade e 14,4 por cento cirurgia cardíaca prévia. Na cirurgia, 87,4 por cento foram submetidos à colocação de prótese aórtica e 12,6 por cento à valvuloplastia aórtica. RESULTADOS: A mortalidade foi de 13,9 por cento (sendo 9,4 por cento de estenose aórtica isolada x 20,9 por cento com procedimento associado; p = 0,023) e a morbidade foi de 30,0 por cento (sendo 25,2 por cento de estenose aórtica isolada x 37,4 por cento com procedimento associado; p = 0,068). As complicações mais frequentes foram: baixo débito cardíaco (20,2 por cento), disfunção renal (9,7 por cento) e suporte ventilatório prolongado (7,9 por cento). Na análise bivariada, os maiores preditores de mortalidade foram: baixo débito cardíaco (RR 10,1, IC95 por cento: 5,02-20,3), uso do balão intra-aórtico (RR 6,6, IC95 por cento: 3,83-11,4), sepse (RR 6,77, IC95 por cento: 1,66-9,48) e disfunção renal pós-operatória (RR 6,21, IC95 por cento: 3,47-11,1). Quanto à morbidade, foram preditores: disfunção renal pré-operatória (RR 2,22, IC95 por cento: 1,25-3,95), fibrilação atrial (RR 1,74, IC95 por cento: 1,16-2,61) e doença pulmonar obstrutiva crônica (DPOC) (RR 1,93, IC95 por cento: 1,25-2,97). CONCLUSÃO: A cirurgia valvar aórtica em idosos está relacionada à morbimortalidade um pouco ...

BACKGROUND: The greater longevity observed today has caused an increase in the number of elderly who need surgery. Aortic stenosis is a common condition in this age group. OBJECTIVE: To evaluate morbidity and mortality in people aged 75 years or older who have undergone valvuloplasty or valve replacement surgery for aortic stenosis alone or associated with other injuries. METHODS: We studied 230 consecutive cases between Jan/2002-Dec/2007. Patients were 79.5 ± 3.7 years (75 - 94), and 53.9 percent were men. In the sample, 68.7 percent had hypertension, 17.9 percent had atrial fibrillation, 15.9 percent were obese, and 14.4 percent had undergone previous heart surgery. At surgery, 87.4 percent underwent aortic stent placement, and 12.6 percent underwent aortic valvuloplasty. RESULTS: The mortality rate was 13.9 percent (9.4 percent with isolated aortic stenosis versus 20.9 percent with an associated procedure, p = 0.023) and the morbidity rate was 30.0 percent (25.2 percent with aortic stenosis alone versus 37.4 percent with an associated procedure, p = 0.068). The most common complications were: low cardiac output (20.2 percent), renal dysfunction (9.7 percent), and prolonged ventilatory support (7.9 percent). In the bivariate analysis, the main predictors of mortality were low cardiac output (RR 10.1, 95 percent CI: 5.02-20.3), use of intra-aortic balloon (RR 6.6, 95 percent CI: 3.83-11.4), sepsis (RR 6.77, 95 percent: 1.66-9.48) and renal dysfunction after surgery (RR 6.21, 95 percent: 3.47-11.1). As for morbidity, the predictors were: pre-operative renal dysfunction (RR 2.22, 95 percent: 1.25-3.95), atrial fibrillation (RR 1.74, 95 percent: 1.16-2.61), and chronic obstructive pulmonary disease (COPD) (RR 1.93, 95 percent: 1.25-2.97). CONCLUSION: Aortic valve surgery in the elderly is related to a slightly higher mortality rate than in younger patients, and its main risk factors were associated procedures, renal failure, atrial fibrillation, ...

[Morbidity and mortality in patients aged over 75 years undergoing surgery for aortic valve replacement].

BACKGROUND: The greater longevity observed today has caused an increase in the number of elderly who need surgery. Aortic stenosis is a common condition in this age group. OBJECTIVE: To evaluate morbidity and mortality in people aged 75 years or older who have undergone valvuloplasty or valve replacement surgery for aortic stenosis alone or associated with other injuries. METHODS: We studied 230 consecutive cases between Jan/2002-Dec/2007. Patients were 79.5 +/- 3.7 years (75 - 94), and 53.9% were men. In the sample, 68.7% had hypertension, 17.9% had atrial fibrillation, 15.9% were obese, and 14.4% had undergone previous heart surgery. At surgery, 87.4% underwent aortic stent placement, and 12.6% underwent aortic valvuloplasty. RESULTS: The mortality rate was 13.9% (9.4% with isolated aortic stenosis versus 20.9% with an associated procedure, p = 0.023) and the morbidity rate was 30.0% (25.2% with aortic stenosis alone versus 37.4% with an associated procedure, p = 0.068). The most common complications were: low cardiac output (20.2%), renal dysfunction (9.7%), and prolonged ventilatory support (7.9%). In the bivariate analysis, the main predictors of mortality were low cardiac output (RR 10.1, 95% CI: 5.02-20.3), use of intra-aortic balloon (RR 6.6, 95% CI: 3.83-11.4), sepsis (RR 6.77, 95%: 1.66-9.48) and renal dysfunction after surgery (RR 6.21, 95%: 3.47-11.1). As for morbidity, the predictors were: pre-operative renal dysfunction (RR 2.22, 95%: 1.25-3.95), atrial fibrillation (RR 1.74, 95%: 1.16-2.61), and chronic obstructive pulmonary disease (COPD) (RR 1.93, 95%: 1.25-2.97). CONCLUSION: Aortic valve surgery in the elderly is related to a slightly higher mortality rate than in younger patients, and its main risk factors were associated procedures, renal failure, atrial fibrillation, COPD, and sepsis.

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.