Gene therapy for refractory angina and cell therapy for heart failure: experience of a Brazilian research group.

Cell therapy has shown impressive effects in experimental cardiomyopathy models. To a lesser extent, gene therapy has also been studied. In both cases, translation to clinical therapy has been disappointing. This paper is intended to describe the experience and achievements of a multicenter working group located in Porto Alegre, southern Brazil, in experimental and translational research projects for cell-based and gene therapy methods in the treatment of dilated and ischemic cardiomyopathies. The results of preclinical and clinical studies showed that bone marrow mononuclear stem cells indeed have an effect in improving myocardial perfusion and contractile function, but the overall results are poorly translated to the clinical level. Gene therapy studies with direct myocardial injections of naked VEGF 165 plasmid showed improvement in myocardial perfusion and function in animal models. A randomized clinical trial found that this method is safe and improved myocardial perfusion, but the benefits disappeared after 1 year. An animal experiment associating VEGF 165 with angiopoietin was undertaken in mini pigs to extend the durability of that therapy. In conclusion, our efforts to better understand the mechanisms and functions of gene and cell-based therapies in cardiology resulted in significant findings and propose a future look at cell-free therapeutic approaches.

Valvuloplasty Without Prosthetic Ring or Band in Patients with Degenerative Mitral Regurgitation: Long-Term Results and Predictive Factors for Outcomes.

INTRODUCTION: Mitral valvuloplasty including ring/band support is widely performed despite potential drawbacks of rings. Unsupported valvuloplasty is performed in only a few centers. This study aimed to report long-term outcomes of patients undergoing unsupported valvuloplasty for degenerative mitral regurgitation (MR) and to identify predictive factors for outcomes. METHODS: This is a retrospective cohort including patients undergoing mitral valve repair for degenerative MR from 2000 to 2018. The main techniques were Wooler annuloplasty and quadrangular resection. Kaplan-Meier curves and Cox regression models were used for statistical analysis. RESULTS: One hundred fifty-eight patients were included (median age: 64.0 years). In-hospital mortality was 2.5%. Maximum followup was 19.6 years, with a median of 4.7 years (992 patient-years). Overall survival at 5, 10, and 15 years was 91.0% (95% confidence interval [CI]: 85.7-96.3), 87.6% (95% CI: 80.7-94.5), and 78.1% (95% CI: 65.9-90.3), respectively. The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II was an independent predictor of late death (hazard ratio [HR] 1.42; P=0.016). Freedom from mitral reoperation at 5, 10, and 15 years was 88.1% (95% CI: 82.0-94.2), 82.4% (95% CI: 74.6-90.2), and 75.7% (95% CI: 64.1-87.3), respectively. Left atrial diameter > 56 mm was associated with late reintervention in univariate analysis (HR 1.06; P=0.049). CONCLUSION: Degenerative MR can be successfully treated with repair techniques without annular support, thus avoiding the technical and logistical drawbacks of ring/band implantation while maintaining good long-term results. EuroSCORE II was a risk factor for late death, and larger left atrium was associated with late reoperation.

Valvuloplasty Without Prosthetic Ring or Band in Patients with Degenerative Mitral Regurgitation: Long-Term Results and Predictive Factors for Outcomes

Abstract Introduction: Mitral valvuloplasty including ring/band support is widely performed despite potential drawbacks of rings. Unsupported valvuloplasty is performed in only a few centers. This study aimed to report long-term outcomes of patients undergoing unsupported valvuloplasty for degenerative mitral regurgitation (MR) and to identify predictive factors for outcomes. Methods: This is a retrospective cohort including patients undergoing mitral valve repair for degenerative MR from 2000 to 2018. The main techniques were Wooler annuloplasty and quadrangular resection. Kaplan-Meier curves and Cox regression models were used for statistical analysis. Results: One hundred fifty-eight patients were included (median age: 64.0 years). In-hospital mortality was 2.5%. Maximum follow-up was 19.6 years, with a median of 4.7 years (992 patient-years). Overall survival at 5, 10, and 15 years was 91.0% (95% confidence interval [CI]: 85.7-96.3), 87.6% (95% CI: 80.7-94.5), and 78.1% (95% CI: 65.9-90.3), respectively. The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II was an independent predictor of late death (hazard ratio [HR] 1.42; P=0.016). Freedom from mitral reoperation at 5, 10, and 15 years was 88.1% (95% CI: 82.0-94.2), 82.4% (95% CI: 74.6-90.2), and 75.7% (95% CI: 64.1-87.3), respectively. Left atrial diameter > 56 mm was associated with late reintervention in univariate analysis (HR 1.06; P=0.049). Conclusion: Degenerative MR can be successfully treated with repair techniques without annular support, thus avoiding the technical and logistical drawbacks of ring/band implantation while maintaining good long-term results. EuroSCORE II was a risk factor for late death, and larger left atrium was associated with late reoperation.

Advanced age and incidence of atrial fibrillation in the postoperative period of aortic valve replacement.

OBJECTIVE: This study aims to describe the correlation between age and occurrence of atrial fibrillation after aortic stenosis surgery in the elderly as well as evaluate the influence of atrial fibrillation on the incidence of strokes, hospital length of stay, and hospital mortality. METHODS: Cross-sectional retrospective study of > 70 year-old patients who underwent isolated aortic valve replacement. RESULTS: 348 patients were included in the study (mean age 76.8±4.6 years). Overall, post-operative atrial fibrillation was 32.8% (n=114), but it was higher in patients aged 80 years and older (42.9% versus 28.8% in patients aged 70-79 years, P=0.017). There was borderline significance for linear correlation between age and atrial fibrillation (P=0.055). Intensive Care Unit and hospital lengths of stay were significantly increased in atrial fibrillation (P<0.001), but there was no increase in mortality or stroke associated with atrial fibrillation. CONCLUSION: Post-operative atrial fibrillation incidence in aortic valve replacement is high and correlates with age in patients aged 70 years and older and significantly more pronounced in patients aged 80 years. There was increased length of stay at Intensive Care Unit and hospital, but there was no increase in mortality or stroke. These data are important for planning prophylaxis and early treatment for this subgroup.

Direct intramyocardial transthoracic transplantation of bone marrow mononuclear cells for non-ischemic dilated cardiomyopathy: INTRACELL, a prospective randomized controlled trial.

OBJECTIVE: We tested the hypothesis that direct intramyocardial injection of bone marrow mononuclear cells in patients with non-ischemic dilated cardiomyopathy can improve left ventricular function and physical capacity. METHODS: Thirty non-ischemic dilated cardiomyopathy patients with left ventricular ejection fraction <35% were randomized at a 1:2 ratio into two groups, control and treated. The bone marrow mononuclear cells group received 1.06±108 bone marrow mononuclear cells through mini-thoracotomy. There was no intervention in the control group. Assessment was carried out through clinical evaluations as well as a 6-min walk test, nuclear magnectic resonance imaging and echocardiogram. RESULTS: The bone marrow mononuclear cells group showed a trend toward left ventricular ejection fraction improvement, with magnectic resonance imaging - at 3 months, showing an increase from 27.80±6.86% to 30.13±9.06% (P=0.08) and returning to baseline at 9 months (28.78%, P=0.77). Magnectic resonance imaging showed no changes in left ventricular ejection fraction during follow-up of the control group (28.00±4.32%, 27.42±7.41%, and 29.57±4.50%). Echocardiogram showed left ventricular ejection fraction improved in the bone marrow mononuclear cells group at 3 months, 25.09±3.98 to 30.94±9.16 (P=0.01), and one year, 30.07±7.25% (P=0.001). The control group showed no change (26.1±4.4 vs 26.5±4.7 and 30.2±7.39%, P=0.25 and 0.10, respectively). Bone marrow mononuclear cells group showed improvement in New York Heart Association functional class, from 3.40±0.50 to 2.41±0.79 (P=0.002); patients in the control group showed no change (3.37±0.51 to 2.71±0.95; P=0.17). Six-minute walk test improved in the bone marrow mononuclear cells group (348.00±93.51m at baseline to 370.41±91.56m at 12 months, P=0.66) and there was a non-significant decline in the control group (361.25±90.78m to 330.00±123.42m after 12 months, P=0.66). Group comparisons were non-significant. CONCLUSION: The trend of intragroup functional and subjective improvement was not confirmed when compared to the control group. Direct intramyocardial application of bone marrow mononuclear cells in non-ischemic dilated cardiomyopathy was not associated with significant changes in left ventricular function. Differences observed within the bone marrow mononuclear cells group could be due to placebo effect or low statistical power.

Results of aortic valve surgery in patients over 75 years old, at 4.5 years of follow-up.

BACKGROUND: The increased longevity elevated the frequency of elderly requiring surgery, among them the correction of aortic stenosis. OBJECTIVES: To evaluate medium-term mortality, need for reoperation for valve replacement and valve complications [systemic thromboembolism (STE) and prosthetic endocarditis (PE)] in patients over 75 years old who had undergone surgery for aortic stenosis. METHODS: Retrospective study of 230 patients from 2002 to 2007. Mean age was 83.4 years and 53% were male. The prevalence of hypertension was 73.2%, atrial fibrillation 17.9% and previous cardiac surgery 14.4%. Another cardiac procedure was associated in 39.1%. RESULTS: In a mean follow-up of 4.51 years the overall survival of the population studied was 57.4%. Death in the immediate postoperative period occurred in 13.9% (9.4% in the isolated aortic stenosis surgery group vs. 20.9% when another procedure was associated). Deaths in the medium term occurred in 28.7% of the patients (25.0% vs. 34.4%), with 34 of these because of cardiovascular causes. There were 6 cases of PE, 8 cases of STE and 6 reoperations. The predictors of mortality were ischemia time >90 min (OR 1.99 95% CI 1.06-3.74), ejection fraction <60% (OR 1.76 95% CI 1.10-2.81) and prior stroke (OR 2.43 95% CI 1.18-5.30). CONCLUSION: Although the immediate surgical risk of the elderly is high, survival rates for surgical treatment of patients over 75 years old are acceptable and allow this intervention. The prognosis is worse especially because of the association with coronary artery disease.

Use of intra-aortic balloon pump in cardiac surgery: analysis of 80 consecutive cases.

BACKGROUND: About 10% to 15% of patients undergoing cardiac surgery may develop low cardiac output syndrome in the perioperative period; of this total, 2% require mechanical support for adequate hemodynamic control. OBJECTIVE: To describe the mortality rates of patients who required the use of IABP in the perioperative or postoperative period of cardiac surgery, identifying preoperative variables associated with a worse outcome, as well as to describe the postoperative complications and medium-term survival. METHODS: Retrospective cohort study including 80 consecutive cases between January/2009 and September/ 2011. The patients had on average 62.9 ± 11.3 years and 58.8% were male; 81.3% were hypertensive, 50.0% had prior myocardial infarction and 38.8% has NYHA III/IV heart failure. The mainsurgery performed was isolated coronary artery bypass grafting (37.5%). RESULTS: Hospital mortality was 53.8% (IC 95%: 42.7-64.9), and cross-clamp time > 90 minutes was an independent predictor of mortality in multivariate analysis (OR 1.52 CI 95%: 1.04-2.22). 71.3% of patients (CI 95%: 61.2-81.4) had at least one additional complication in the perioperative period, with lower limb ischemia observed in 5.0% patients. One-year survival was 43.6%, with a plateau in survival rates after a sharp initial drop, related to hospital mortality. CONCLUSION: Patients who require IABP comprise a group of very high risk for morbidity and mortality. IABP use, however, enables the recovery of many patients from an evolution that would invariably be fatal, and patients discharged from hospital have a good medium-term survival.

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.

Idade avançada e incidência de fibrilação atrial em pós-operatório de troca valvar aórtica / Advanced age and incidence of atrial fibrillation in the postoperative period of aortic valve replacement

Objetivo: Descrever, em idosos, a correlação entre faixa etária e ocorrência de fibrilação atrial após cirurgia por estenose aórtica, além de avaliar a influência da ocorrência de fibrilação atrial na incidência de acidente vascular cerebral, tempo de internação e mortalidade hospitalar. Métodos: Estudo transversal retrospectivo incluindo pacientes com idade > 70 anos submetidos à cirurgia de troca valvar aórtica isolada. Resultados: Foram estudados 348 pacientes com idade média de 76,8±4,6 anos. A incidência de fibrilação atrial no pós-operatório foi 32,8% (n=114), sendo superior nos pacientes > 80 anos (42,9 vs. 28,8% 70-79 anos, P=0,017) e havendo significância estatística limítrofe (P=0,055) para tendência linear na correlação idade e incidência de fibrilação atrial. Verificou-se significativo maior tempo de internação na Unidade de Terapia Intensiva e hospitalar total, porém, não se observou maior taxa de acidente vascular cerebral ou de mortalidade hospitalar decorrente da fibrilação atrial. Conclusão: A incidência de fibrilação atrial no pós-operatório de cirurgia para estenose valvar aórtica em pacientes idosos com > 70 anos foi elevada e linearmente correlacionada ao avanço da idade, especialmente após 80 anos, causando aumento dos tempos de internação total e em Unidade de Terapia Intensiva, sem aumento significativo da morbimortalidade. O conhecimento desses dados é importante para evidenciar a necessidade de medidas profiláticas e de tratamento precoce dessa arritmia nesse subgrupo. .

Objective: This study aims to describe the correlation between age and occurrence of atrial fibrillation after aortic stenosis surgery in the elderly as well as evaluate the influence of atrial fibrillation on the incidence of strokes, hospital length of stay, and hospital mortality. Methods: Cross-sectional retrospective study of > 70 year-old patients who underwent isolated aortic valve replacement. Results: 348 patients were included in the study (mean age 76.8±4.6 years). Overall, post-operative atrial fibrillation was 32.8% (n=114), but it was higher in patients aged 80 years and older (42.9% versus 28.8% in patients aged 70-79 years, P=0.017). There was borderline significance for linear correlation between age and atrial fibrillation (P=0.055). Intensive Care Unit and hospital lengths of stay were significantly increased in atrial fibrillation (P<0.001), but there was no increase in mortality or stroke associated with atrial fibrillation. Conclusion: Post-operative atrial fibrillation incidence in aortic valve replacement is high and correlates with age in patients aged 70 years and older and significantly more pronounced in patients aged 80 years. There was increased length of stay at Intensive Care Unit and hospital, but there was no increase in mortality or stroke. These data are important for planning prophylaxis and early treatment for this subgroup. .

Direct intramyocardial transthoracic transplantation of bone marrow mononuclear cells for non-ischemic dilated cardiomyopathy: INTRACELL, a prospective randomized controlled trial / Ensaio clínico prospectivo randomizado sobre terapia com células mononucleares da medula óssea para cardiomiopatia dilatada idiopática: INTRACELL

Objective: We tested the hypothesis that direct intramyocardial injection of bone marrow mononuclear cells in patients with non-ischemic dilated cardiomyopathy can improve left ventricular function and physical capacity. Methods: Thirty non-ischemic dilated cardiomyopathy patients with left ventricular ejection fraction <35% were randomized at a 1:2 ratio into two groups, control and treated. The bone marrow mononuclear cells group received 1.06±108 bone marrow mononuclear cells through mini-thoracotomy. There was no intervention in the control group. Assessment was carried out through clinical evaluations as well as a 6-min walk test, nuclear magnectic resonance imaging and echocardiogram. Results: The bone marrow mononuclear cells group showed a trend toward left ventricular ejection fraction improvement, with magnectic resonance imaging - at 3 months, showing an increase from 27.80±6.86% to 30.13±9.06% (P=0.08) and returning to baseline at 9 months (28.78%, P=0.77). Magnectic resonance imaging showed no changes in left ventricular ejection fraction during follow-up of the control group (28.00±4.32%, 27.42±7.41%, and 29.57±4.50%). Echocardiogram showed left ventricular ejection fraction improved in the bone marrow mononuclear cells group at 3 months, 25.09±3.98 to 30.94±9.16 (P=0.01), and one year, 30.07±7.25% (P=0.001). The control group showed no change (26.1±4.4 vs 26.5±4.7 and 30.2±7.39%, P=0.25 and 0.10, respectively). Bone marrow mononuclear cells group showed improvement in New York Heart Association functional class, from 3.40±0.50 to 2.41±0.79 (P=0.002); patients in the control group showed no change (3.37±0.51 to 2.71±0.95; P=0.17). Six-minute walk test improved in the bone marrow mononuclear cells group (348.00±93.51m at baseline to 370.41±91.56m at 12 months, P=0.66) and there was a non-significant decline in the control group ...

Objetivo: Testamos a hipótese de que a injeção intramiocárdica direta de células mononucleares de medula óssea em pacientes portadores de cardiomiopatia dilatada não-isquêmica pode melhorar a função ventricular e a capacidade física. Métodos: Trinta pacientes com cardiomiopatia dilatada não isquêmica e fração de ejeção 35% foram randomizados na razão 1:2 em grupos controle e tratado. Grupo células mononucleares de medula óssea recebeu 1,06 ± 108 células mononucleares de medula óssea por mini-toracotomia. Grupo controle não recebeu intervenção. Avaliação foi feita clinicamente e por teste de caminhada 6 minutos (T6m), ressonância magnética e ecocardiogramas. Resultados: Grupo células mononucleares de medula óssea mostrou tendência de melhora da Fração de ejeção - ressonância magnética aos 3 meses, 27,80±6,86% para 30,13±9,06% (P=0,08), retornando ao basal aos 9 meses (28,78%, P=0,77). Grupo controle não apresentou variação (28,00±4,32%; 27,42±7,41% e 29,57±4,50%). Ecocardiogramas - fração de ejeção melhorou no grupo células mononucleares de medula óssea aos 3 meses: 25,09±3,98 para 30,94±9,16 (P=0,01) e aos 12 meses (30,07±7,25%, P=0,001), enquanto o controle não variou: 26,1±4,4 vs. 26,5±4,7 e 30,2±7,39%, P=0,25 e 0,10, respectivamente). Células mononucleares de medula óssea melhorou classe funcional New York Heart Association: 3,40±0.50 para 2,41±0,79 (P=0,002); controles não mudaram (3,37±0,51 para 2,71±0,95; P=0,17). T6m melhorou no grupo células mononucleares de medula óssea (348,00±93,51 m inicial para 370,41±91,56 m aos 12 m, P=0,66) e declinou sem significância no ...

Uso do balão intra-aórtico no trans e pós-operatório de cirurgia cardíaca: análise de 80 casos consecutivos / Use of intra-aortic balloon pump in cardiac surgery: analysis of 80 consecutive cases

FUNDAMENTO: A síndrome de baixo débito cardíaco no perioperatório de cirurgia cardíaca pode incidir em cerca de 10 a 15% dos pacientes; desse total, 2% necessitam de suporte mecânico para adequado controle hemodinâmico. OBJETIVOS: Descrever a mortalidade de pacientes que necessitaram utilizar balão intra-aórtico (BIAo) no trans ou pós-operatório de cirurgia cardíaca, identificando variáveis pré-operatórias associadas a pior desfecho, assim como descrever as complicações pós-operatórias e a sobrevida em médio prazo. MÉTODOS: Estudo de coorte retrospectivo incluindo 80 casos consecutivos entre janeiro/2009 e setembro/2011. Os pacientes possuíam, em média, 62,9 ± 11,3 anos e 58,8% eram do sexo masculino. Na amostra, 81,3% dos pacientes eram hipertensos, 50% tinham infarto do miocárdio prévio e 38,8%, insuficiência cardíaca NYHA III/IV. A principal cirurgia realizada foi a revascularização miocárdica isolada (37,5%). RESULTADOS:A mortalidade hospitalar nesta série foi de 53,8% (IC95%: 42,7-64,9), sendo o tempo de isquemia > 90 minutos preditor independente de mortalidade em análise multivariada (RR 1,52 IC95%: 1,04-2,22). Em relação às complicações, 71,3% (IC95%: 61,2-81,4) dos pacientes apresentaram ao menos uma complicação adicional no período perioperatório, sendo a isquemia do membro inferior observada em 5% dos pacientes. A sobrevida em 1 ano foi de 43,6%, observando-se um platô na curva de sobrevida após uma queda acentuada inicial, relacionada à mortalidade hospitalar. CONCLUSÕES: Os pacientes que necessitam do BIAo compõem um grupo de muito alto risco para morbidade e mortalidade; seu emprego, entretanto, permite recuperar muitos pacientes de uma evolução que seria invariavelmente fatal, tendo os pacientes com alta hospitalar uma boa sobrevida em médio prazo.

BACKGROUND: About 10% to 15% of patients undergoing cardiac surgery may develop low cardiac output syndrome in the perioperative period; of this total, 2% require mechanical support for adequate hemodynamic control. OBJECTIVE: To describe the mortality rates of patients who required the use of IABP in the perioperative or postoperative period of cardiac surgery, identifying preoperative variables associated with a worse outcome, as well as to describe the postoperative complications and medium-term survival. METHODS: Retrospective cohort study including 80 consecutive cases between January/2009 and September/ 2011. The patients had on average 62.9 ± 11.3 years and 58.8% were male; 81.3% were hypertensive, 50.0% had prior myocardial infarction and 38.8% has NYHA III/IV heart failure. The mainsurgery performed was isolated coronary artery bypass grafting (37.5%). RESULTS: Hospital mortality was 53.8% (IC 95%: 42.7-64.9), and cross-clamp time > 90 minutes was an independent predictor of mortality in multivariate analysis (OR 1.52 CI 95%: 1.04-2.22). 71.3% of patients (CI 95%: 61.2-81.4) had at least one additional complication in the perioperative period, with lower limb ischemia observed in 5.0% patients. One-year survival was 43.6%, with a plateau in survival rates after a sharp initial drop, related to hospital mortality. CONCLUSION: Patients who require IABP comprise a group of very high risk for morbidity and mortality. IABP use, however, enables the recovery of many patients from an evolution that would invariably be fatal, and patients discharged from hospital have a good medium-term survival.

Resultados da cirurgia por estenose aórtica em pacientes acima de 75 anos, em 4,5 anos de seguimento / Results of aortic valve surgery in patients over 75 years old, at 4.5 years of follow-up

INTRODUÇÃO: O aumento da expectativa de vida da população tem levado à maior necessidade de intervenções cirúrgicas sobre a valva aórtica. OBJETIVOS: Avaliar a mortalidade precoce e a médio prazo, a necessidade de reoperação para troca valvar e complicações valvares [tromboembolismo sistêmico (TES) e endocardite infecciosa em prótese (EI)] em pacientes acima de 75 anos submetidos a cirurgia de estenose aórtica. MÉTODOS: Estudo retrospectivo de 230 casos, operados no período de 2002 a 2007. A idade média foi de 83,4 anos, sendo 53% do sexo masculino, 73,2% hipertensos, 17,9% portadores de fibrilação atrial e 14,4% com cirurgia cardíaca prévia. Outro procedimento cardíaco esteve associado em 39,1% dos casos. RESULTADOS: Em 4,51 anos de seguimento médio, a sobrevida geral foi de 57,4%. Ocorreram 13,9% óbitos intra-hospitalares (9,4% no grupo cirurgia de estenose aórtica isolada vs. 20,9% quando outro procedimento cirúrgico foi associado) e 28,7% óbitos após a alta hospitalar (25,0% vs. 34,4%), com 34 destes por causas cardiovasculares. Ocorreram seis casos de EI, oito casos de TES e seis reoperações para troca valvar. Os preditores de mortalidade geral foram: tempo de isquemia >90 min (RC 1,99 IC 95% 1,06-3,74), fração de ejeção <60% (RC 1,76 IC 95% 1,10-2,81) e acidente vascular encefálico prévio (RC 2,43 IC 95% 1,18-5,30). CONCLUSÃO: Ainda que o risco cirúrgico imediato de idosos seja elevado, as taxas de sobrevida referentes ao tratamento cirúrgico em pacientes acima de 75 anos são aceitáveis e permitem essa intervenção. O prognóstico é agravado, sobretudo, pela associação com doença arterial coronariana.

BACKGROUND: The increased longevity elevated the frequency of elderly requiring surgery, among them the correction of aortic stenosis. OBJECTIVES: To evaluate medium-term mortality, need for reoperation for valve replacement and valve complications [systemic thromboembolism (STE) and prosthetic endocarditis (PE)] in patients over 75 years old who had undergone surgery for aortic stenosis. METHODS: Retrospective study of 230 patients from 2002 to 2007. Mean age was 83.4 years and 53% were male. The prevalence of hypertension was 73.2%, atrial fibrillation 17.9% and previous cardiac surgery 14.4%. Another cardiac procedure was associated in 39.1%. RESULTS: In a mean follow-up of 4.51 years the overall survival of the population studied was 57.4%. Death in the immediate postoperative period occurred in 13.9% (9.4% in the isolated aortic stenosis surgery group vs. 20.9% when another procedure was associated). Deaths in the medium term occurred in 28.7% of the patients (25.0% vs. 34.4%), with 34 of these because of cardiovascular causes. There were 6 cases of PE, 8 cases of STE and 6 reoperations. The predictors of mortality were ischemia time >90 min (OR 1.99 95% CI 1.06-3.74), ejection fraction <60% (OR 1.76 95% CI 1.10-2.81) and prior stroke (OR 2.43 95% CI 1.18-5.30). CONCLUSION: Although the immediate surgical risk of the elderly is high, survival rates for surgical treatment of patients over 75 years old are acceptable and allow this intervention. The prognosis is worse especially because of the association with coronary artery disease.

Terapia gênica com VEGF para angiogênese na angina refratária: ensaio clínico fase I/II / VEGF gene therapy for angiogenesis in refractory angina: phase I/II clinical trial

OBJETIVO: Avaliar a segurança, viabilidade e efeitos iniciais, clínicos e sobre a perfusão miocárdica, da administração intramiocárdica, transtorácica, de VEGF 165 plasmidial em pacientes com doença arterial coronariana avançada e angina refratária, não passíveis de revascularização percutânea e cirúrgica. MÉTODOS: Ensaio clínico fase I/II. Treze pacientes cardiopatas isquêmicos com angina refratária apesar de tratamento medicamentoso máximo por no mínimo seis meses, não passíveis de revascularização cirúrgica ou por cateter foram submetidos a injeções intramiocárdicas de 2000µg VEGF 165 plasmidial. Os pacientes foram avaliados por cintilografia miocárdica, teste ergométrico, questionário de qualidade de vida (Minnesota) e determinação das classes de insuficiência cardíaca (NYHA) e angina (CCS). RESULTADOS: Não houve óbitos ou reintervenções. Durante o período de tratamento medicamentoso máximo, não se observou diferenças em cintilografias miocárdicas, testes ergométricos e questionários de qualidade de vida, ainda, houve tendência a piora das classes NYHA (P=0,05) e CCS (P=0,05). Três meses após intervenção, observou-se melhora dos escores cintilográficos SSS (18,38±7,51 vs. 15,31±7,29, P=0,003) e SRS (11,92±7,49 vs. 8,53±6,68, P=0,002), porém não na proporção da extensão da área de miocárdio isquêmico (23,38±13,12 por cento vs. 20,08±13,88 por cento, P=0,1). Houve tendência a melhora dos METs nas ergometrias (7,66±4,47 vs. 10,29±4,36, P=0,08), melhora do escore de qualidade de vida (48,23±18,35 vs. 30,15±20,13; P=0,02) e das classes NYHA (3,15±0,38 vs. 1,77±0,83, P=0,001) e CCS (3,08±0,64 vs. 1,77±0,83, P=0,001), no mesmo período. CONCLUSÕES: A terapia demonstrou-se segura e viável nesta série de pacientes. Os resultados iniciais tendem a demonstrar melhora na gravidade da angina e redução da intensidade da isquemia miocárdica.

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 5mL 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, Minnesotta 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 percent vs. 20.08±13.88 percent, 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.

Evoluçãode crianças com idade inferior a 2 anos submetidas a implante de marcapasso cardíaco permanente / late results with permanent cardiac pacing in children less than two years of age

A estimulação epicárdica predomina no implante de marcapasso em crianças pequenas. Objetivo: revisar a evolução de pacientes menores de dois anos submetidos a estimulação epimiocárdica após a alta hospitalar e até uma década. Método: Estudo de coorte histórica entre 1997 e 2010 que incluiu 34 pacientes, 22 (64,7%) do sexo feminino e 12 (35,3%) do masculino, com idades variando de 1 dia a 22 meses, submetidos a implante de marcapasso utilizando cabo-eletrodo epimiocárdico sem sutura e gerador unicameral (VVI). A arritmia pre dominante foi o bloqueio atrioventricular (n=30; 88,2%); 29 (85,3%) tinham cardiopatia estrutural e 22 (67,4%) haviam sido previamente submetidos a cirurgia cardíaca. Acompanhados durante um tempo médio de 60,5 meses, tiveram registrados os eventos adversos e calculada a probabilidade de sobrevida conforme Kaplan-Meyer. Resultados: Ocorreram três óbitos (8,8%) por infecção, cirurgia cardíaca ou mal súbito. A mortalidade foi superior naqueles sem cirurgia cardíaca prévia (16,7% versus 4,5%). Ao longo do acompanhamento, cinco pacientes (14,7%) necessitaram de nova intervenção, dois por infecção e três para reimplante de cabo-eletrodo. Um dos pacientes submetidos a nova intervenção por infecção evoluiu para óbito. A probabilidade de sobrevida foi de 93,8% no primeiro ano e 90,3% até 10º ano. A sobrevida livre de eventos adversos foi de 90,8% no primeiro ano, 79,8% do 5º ao 9º e 66,5% no 10º ano. Conclusão: Os resultados evidenciam sobrevida satisfatória das crianças após o implante epicárdico, especialmente aquelas com cirurgia cardíaca prévia. O implante de cabo-eletrodo epimiocárdico merece cuidados adicionais em pacientes com estatura reduzida, malformações cardíacas específicas, acesso dificultado à veia cava superior ou com procedimento cirúrgico associado...

Objective: Epicardial stimulation remains the technique of choice for pacing in small children. Our objective is to review the results of epicardial pacemaker implantation in patients with less than 2 years of age and after hospital discharge. Methods: Historical cohort study including 34 patients with age ranging from one day to 22 months with hospital discharge after permanent pacemaker implantation with a sutureless epimyocardial electrode and single chamber generator (VVI mode) between 1997 and 2010. Twenty-two patients were female and 12 male. Predominant arrhythmia was atrioventricular block (30 patients; 88.2%). Twenty-nine patients (85.3%) had structural heart disease and 22 (67.4%) had been submitted to a previous heart surgery. Patients were followed-up for a mean time of 60.5 months. Recorded events were analyzed and probability of survival was estimated according to Kaplan-Meyer analysis. Results: There were 3 (8.8%) deaths, due to infection, heart surgery or sudden death. Increased mortality was observed for patients without previous heart surgery (16.7% versus 4.5%). Five patients (14.7%) required pacemaker reintervention during the follow-up, 2 due to infection and 3 to re-implant the electrode. One of the patients who had a reintervention due to infection died. Probability of survival was 93.8% in the first year and 90.3% subsequently up to the 10 years of follow-up. Event-free survival was 90.8% in the first year, 79.8% from year 5 to 9, 66.5% after 10 years. Conclusion: This study demonstrates the probability of satisfactory survival after epicardial pacemaker implantation, especially in patients with previous heart surgery. Epimyocardial electrode implantation deserves consideration in patients with small physical structure, those with specific cardiac malformations, and difficult access to superior vena cava or those who need to have an associated surgical procedure...

Técnica do "duplo patch" para correção cirúrgica dos defeitos atrioventriculares / Double patch technic for surgical correction of atrioventricular defects

Oito portadores de defeitos atrioventriculares (DAV), com idades entre 11 meses e 19 anos, foram operados com o emprego do "duplo patch", sendo que 5 deles tinham insuficiência mitral pré-operatória. Dois eram do tipo C e os demais, do tipo A. Em uma paciente de 19 anos, com importante insuficiência da valva A-V comum, a técnica do "duplo patch" foi acompanhada de anuloplastia de De Vega no anel tricuspide e autoplastia de Whooler no anel mitral. O estudo hemodinamico pós-operatório detectou insuficiência mitral acentuada e presenca de pequena comunicação interventricular (CIV). Foi reoperada em 15 dias, tendo sido substituida a valva mitral e fechada a CIV. Faleceu nas primeiras horas de pos-operatorio. Os autros 7 pacientes apresentam boa evolução pós-operatória e, em todos, a ausculta e normal sem evidencias clinicas de insuficiência mitral. Concluiu-se que a técnica e aplicável aos três tipos anatômicos de DAV, permite a reconstrução dos componentes da valva A-V comum de maneira simples e sem desfazer a arquitetura valvar, segundo o conceito de Carpentier e o dispositivo, para perfusão cardíaca dissociada da circulação extracorpórea sistemica, e util recurso para correção adequada do defeito

Determinantes do risco pós-operatório imediato no implante de marca-passo cardíaco artificial permanente / Determinants of immediate postoperative risk in the implantation of permanent artificial cardiac pacemaker

Uma serie de 430 pacientes, com disturbio de conducao atrioventricular (AV), submetidos ao implante de marcapasso cardiaco artificial permanente ( MPCAP ), de 1970 a 1981, foi estudada retrospectivamente, buscando-se determinar a mortalidade imediata ( ate 30 dias de pos-operatorio ) e identificar a influencia das caracteristicas dos enfermos (sexos, idade, causa e tipo de disturbio da conducao AV, classe funcional conforme criterios da New York Heart Association, presenca de insuficiencia cardiaca congestiva), da epoca da operacao e da tecnica do implante do MPCAP sobre os resultados. A mortalidade pos-operatoria imediata foi de 3,72% e as caracteristicas da populacao relacionadas com o aumento do risco foram: a idade superior a 60 anos (P<0,05) a classe funcional (p<0,001), a presenca de insuficiencia cardiaca congestiva (0<0,05) e o quadrienio inicial do periodo estudado (p>0,01). Estes resultados possibilitam identificar os pacientes de maior risco no pos-operatorio imediato e a instituicao de medidas que podem reduzir a mortalidade

Fatores que interferem na sobrevivência de pacientes com marca-passo cardíaco artificial permanente / Factors interfering on the survival of patients with permanent artificial pacemaker

Numa serie de 430 pacientes com disturbio de conducao atrioventricular (A-V), submetido ao implante de marcapasso cardiaco artificial permanente (MPCAP), de 1970 a 1981, foi estudada a mortalidade imediata (ate 30 dias apos a operacao, 3,72%), e a tardia (7,25%), sendo esta determinada, primordialmente, por causas nao relacionadas ao MPCAP. A proporcao de sobreviventes foi 92,97% no 1o. ano, 90,51% no 2o. ano, 81,15% no 5o. ano e 76,15% do 7o. ao 10o.ano de pos-operatorio. Pacientes com mais de 60 anos, pertencentes as classes funcionais III e IV, com insuficiencia cardiaca congestiva ou operados no quadrienio inicial mostraram proporcao de sobreviventes significativamente menor em, pelo menos, um dos intervalos anuais, quando comparados aos doentes que nao apresentavam estas caracteristicas. Os resultados indicam que a sobrevivencia de pacientes com MPCAP e superior a descrita na literatura para aqueles com bloqueio A-V total que nao foram submetidos a esta forma de tratamento (aproximadamente 50% no 1o. ano apos o diagnostico) e possibilitam identificar pacientes de maior risco no pos-operatorio tardio

O marca-passo cardíaco artificial permanente em pacientes submetidos a cirurgia cardíaca / Permanent cardiac artificial pacemaker in patients subjected to heart surgery

Entre 1971 e 1985, o implante de marca-passo cardíaco artificial permanente (MPCAP) foi necessário em 38 pacientes submetidos a cirurgia cardíaca (CC). A cardiopatia que motivou CC era congênita em 9 e adquirida em 29 pacientes (valvar em 17, isquêmica em 11 e miocardiopatias em 1) e a arritmia que requereu implante do MPCAP foi diagnosticada, no pré-operatório, em 5 pacientes, ocorreu por trauma cirúrgico em 19 e manifestou-se tardiamente em 14 pacientes. A técnica de implante do MPCAP foi a transvenosa em 20 e transtorácica em 18. Originalmente, foi utilizada a estimulaçäo ventricular de demanda em 37 procedimentos e um paciente recebeu MPCAP atrioventricular seqüencial. Näo ocorreram óbitos durante o implante de MPCAP simultâneo (n=10) ou posterior (n=28) à CC, mas, tardiamente, 3 pacientes faleceram, sendo dois por insuficiência cardíaca congestiva e outro por arritmia ventricular. O acompanhamento pós-operatório mostrou diversos eventos implicando em nova CC, reprogramaçäo ou reimplante de MPCAP, mas a evoluçäo clínica tem sido satisfatória para os pacientes sobreviventes. Concluiu-se que a associaçäo de CC e MPCAP contribuiu para uma sobrevivência adequada, resguardadas, a necessidade de um acompanhamento pós-operatório criterioso e a versatilidade nas técnicas e modos de estimulaçäo cardíaca artificial

Valvoplastia para insuficiencia mitral: tecnicas e resultados. / Valvuloplasty for mitral valve insufficiency: techniques and results

O valor da valvoplastia no tratamento cirurgico da insuficiencia mitral continua sendo muito discutido. Analisamos neste trabalho, os resultados obtidos em 27 pacientes operados entre 1974 e 1980. A idade variou de 4 a 56 anos (media 26,4). A etiologia reumatica foi a predominante (89%) e 12 casos apresentavam lesoes valvares associadas (44%). Algumas tecnicas operatorias foram empregadas.Houve um obito hospitalar (3,7%) aos 40 dias de pos-operatorio, por agravamento de miocardiopatia existente e um obito tardio (3,7%) aos 39 meses de pos-operatorio, por morte subita. Quatro pacientes estao sem acompanhamento recente. Dos 21 restantes (84%), ha 4 (19%) em grau II (NYHA) e 17 (81%) estao sem sintomas cardiovasculares. Os pacientes sao avaliados periodicamente em ambulatorio e por metodos nao-invasivos. Angiografia foi realizada em 2 pacientes, ambos assintomaticos.Nao houve indicacao de reintervencao cirurgica ate o momento. Ausculta-se sopro sistolico + ou ++/6 em 10 pacientes, cuja evolucao e estavel. Conclui-se que a conservacao da valva mitral, pelas tecnicas empregadas, constitui recurso preferencial em relacao a substituicao valvar. Os resultados, nos periodos estudados, consistentes e duradouros, apoiam essa conclusao

Correcao da coartacao da aorta pela istmoplastia com a arteria subclavia esquerda em pacientes sintomaticos no primeiro ano de vida. / Repair of aortic coarctation by isthmoplasty with left subclavian artery in symptomatic patients in the 1st year of life

Oito pacientes, portadores de coartacao de aorta e idade variando entre 29 dias e 5 meses, foram operados no Instituto de Cardiologia do Rio Grande do Sul, pela tecnica da istmoplastia com a arteria subclavia esquerda Todos possuiam canal arterial persistente e 5 tinham outro defeito intracardiaco associado.Tres pacientes tiveram a bandagem da arteria pulmonar como procedimento associado. Houve 1 obito nas 24 horas de pos-operatorio e os 7 pacientes sobreviventes apresentam pulsos pediosos normalmente palpaveis e cifras tensionais normais nos membros superiores num periodo de acompanhamento de 2 a 30 meses de pos-operatorio. Dois pacientes foram cateterizados novamente, nao apresentando gradiente na zona de anastomose