Implante Percutâneo Transeptal de Bioprótese em Disfunção de Prótese Valvar Cirúrgica Mitral - Experiência Multicêntrica Brasileira / Percutaneous Transseptal Bioprosthetic Implantation in Failed Prosthetic Surgical Mitral Valve - Brazilian Multicenter Experience

Resumo Fundamento A intervenção percutânea em pacientes com disfunção de prótese biológica mitral apresenta-se como uma alternativa ao tratamento cirúrgico convencional. Objetivo Relatar a primeira experiência brasileira de implante transcateter de bioprótese valve-in-valve mitral via transeptal (TMVIV-via transeptal). Métodos Foram incluídos pacientes portadores de disfunção de bioprótese cirúrgica submetidos ao TMVIV-transeptal em 12 hospitais brasileiros. Foram considerados estatisticamente significativos valores de p<0,05. Resultados Entre junho/2016 e fevereiro/2019, 17 pacientes foram submetidos ao TMVIV-via transeptal. A mediana de idade foi 77 anos (IIQ,70-82), a mediana do escore STS-PROM foi 8,7% (IIQ,7,2-17,8). Todos os pacientes tinham sintomas limitantes de insuficiência cardíaca (CF≥III), tendo 5 (29,4%) sido submetidos a mais de uma toracotomia prévia. Obteve-se sucesso do TMVIV-via transeptal em todos os pacientes. A avaliação ecocardiográfica demonstrou redução significativa do gradiente médio (pré-intervenção, 12±3,8 mmHg; pós-intervenção, 5,3±2,6 mmHg; p<0,001), assim como aumento da área valvar mitral (pré-intervenção, 1,06±0,59 cm2; pós-intervenção, 2,18±0,36 cm2; p<0,001) sustentados em 30 dias. Houve redução significativa e imediata da pressão sistólica de artéria pulmonar, com redução adicional em 30 dias (pré-intervenção, 68,9±16,4 mmHg; pós-intervenção, 57,7±16,5 mmHg; 30 dias, 50,9±18,7 mmHg; p<0,001). Durante o seguimento, com mediana de 162 dias (IIQ, 102-411), observou-se marcada melhora clínica (CF≤II) em 87,5%. Um paciente (5,9%) apresentou obstrução de via de saída de ventrículo esquerdo (VSVE), evoluindo para óbito logo após o procedimento, e outro morreu aos 161 dias de seguimento.Conclusão: A primeira experiência brasileira de TMVIV-transeptal demonstra a segurança e a efetividade dessa nova técnica. A obstrução da VSVE é uma complicação potencialmente fatal, reforçando a importância da seleção dos pacientes e do planejamento do procedimento. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Abstract Background Percutaneous intervention in patients with bioprosthetic mitral valve dysfunction is an alternative to conventional surgical treatment. Objectives To report the first Brazilian experience with transseptal transcatheter bioprosthetic mitral valve-in-valve implantation (transseptal-TMVIV). Methods Patients with surgical bioprosthetic dysfunction submitted to transseptal-TMVIV in 12 Brazilian hospitals were included. The significance level adopted was p<0.05. Results From June/2016 to February/2019, 17 patients underwent transseptal-TMVIV. Their median age was 77 years (IQR,70-82) and median Society of Thoracic Surgeons predicted risk of mortality (STS-PROM) score was 8.7% (IQR,7.2-17.8). All patients had limiting symptoms of heart failure (FC≥III) and 5 (29.4%) had undergone more than one previous thoracotomy. Transseptal-TMVIV was successful in all patients. Echocardiographic assessment showed a significant reduction in mean mitral valve gradient (pre-intervention, 12±3.8 mmHg; post-intervention, 5.3±2.6 mmHg; p<0.001), in addition to an increase in mitral valve area (pre-intervention, 1.06±0.59 cm2; post-intervention, 2.18±0.36 cm2; p<0.001) sustained for 30 days. There was a significant and immediate reduction in the pulmonary artery systolic pressure, with an additional reduction in 30 days (pre-intervention, 68.9±16.4 mmHg; post-intervention, 57.7±16.5 mmHg; 30 days, 50.9±18.7 mmHg; p<0.001). During follow-up (median, 162 days; IQR, 102-411), significant clinical improvement (FC≤II) was observed in 87.5% of the patients. One patient (5.9%) had left ventricular outflow tract (LVOT) obstruction and died right after the procedure, and another died at 161 days of follow-up. Conclusion The first Brazilian experience with transseptal-TMVIV shows the safety and effectivity of the new technique. The LVOT obstruction is a potentially fatal complication, reinforcing the importance of patients' selection and of procedural planning. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Percutaneous Transseptal Bioprosthetic Implantation in Failed Prosthetic Surgical Mitral Valve - Brazilian Multicenter Experience. / Implante Percutâneo Transeptal de Bioprótese em Disfunção de Prótese Valvar Cirúrgica Mitral ­ Experiência Multicêntrica Brasileira.

BACKGROUND: Percutaneous intervention in patients with bioprosthetic mitral valve dysfunction is an alternative to conventional surgical treatment. OBJECTIVES: To report the first Brazilian experience with transseptal transcatheter bioprosthetic mitral valve-in-valve implantation (transseptal-TMVIV). METHODS: Patients with surgical bioprosthetic dysfunction submitted to transseptal-TMVIV in 12 Brazilian hospitals were included. The significance level adopted was p<0.05. RESULTS: From June/2016 to February/2019, 17 patients underwent transseptal-TMVIV. Their median age was 77 years (IQR,70-82) and median Society of Thoracic Surgeons predicted risk of mortality (STS-PROM) score was 8.7% (IQR,7.2-17.8). All patients had limiting symptoms of heart failure (FC≥III) and 5 (29.4%) had undergone more than one previous thoracotomy. Transseptal-TMVIV was successful in all patients. Echocardiographic assessment showed a significant reduction in mean mitral valve gradient (pre-intervention, 12±3.8 mmHg; post-intervention, 5.3±2.6 mmHg; p<0.001), in addition to an increase in mitral valve area (pre-intervention, 1.06±0.59 cm2; post-intervention, 2.18±0.36 cm2; p<0.001) sustained for 30 days. There was a significant and immediate reduction in the pulmonary artery systolic pressure, with an additional reduction in 30 days (pre-intervention, 68.9±16.4 mmHg; post-intervention, 57.7±16.5 mmHg; 30 days, 50.9±18.7 mmHg; p<0.001). During follow-up (median, 162 days; IQR, 102-411), significant clinical improvement (FC≤II) was observed in 87.5% of the patients. One patient (5.9%) had left ventricular outflow tract (LVOT) obstruction and died right after the procedure, and another died at 161 days of follow-up. CONCLUSION: The first Brazilian experience with transseptal-TMVIV shows the safety and effectivity of the new technique. The LVOT obstruction is a potentially fatal complication, reinforcing the importance of patients' selection and of procedural planning. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

FUNDAMENTO: A intervenção percutânea em pacientes com disfunção de prótese biológica mitral apresenta-se como uma alternativa ao tratamento cirúrgico convencional. OBJETIVO: Relatar a primeira experiência brasileira de implante transcateter de bioprótese valve-in-valve mitral via transeptal (TMVIV-via transeptal). MÉTODOS: Foram incluídos pacientes portadores de disfunção de bioprótese cirúrgica submetidos ao TMVIV-transeptal em 12 hospitais brasileiros. Foram considerados estatisticamente significativos valores de p<0,05. RESULTADOS: Entre junho/2016 e fevereiro/2019, 17 pacientes foram submetidos ao TMVIV-via transeptal. A mediana de idade foi 77 anos (IIQ,70-82), a mediana do escore STS-PROM foi 8,7% (IIQ,7,2-17,8). Todos os pacientes tinham sintomas limitantes de insuficiência cardíaca (CF≥III), tendo 5 (29,4%) sido submetidos a mais de uma toracotomia prévia. Obteve-se sucesso do TMVIV-via transeptal em todos os pacientes. A avaliação ecocardiográfica demonstrou redução significativa do gradiente médio (pré-intervenção, 12±3,8 mmHg; pós-intervenção, 5,3±2,6 mmHg; p<0,001), assim como aumento da área valvar mitral (pré-intervenção, 1,06±0,59 cm2; pós-intervenção, 2,18±0,36 cm2; p<0,001) sustentados em 30 dias. Houve redução significativa e imediata da pressão sistólica de artéria pulmonar, com redução adicional em 30 dias (pré-intervenção, 68,9±16,4 mmHg; pós-intervenção, 57,7±16,5 mmHg; 30 dias, 50,9±18,7 mmHg; p<0,001). Durante o seguimento, com mediana de 162 dias (IIQ, 102-411), observou-se marcada melhora clínica (CF≤II) em 87,5%. Um paciente (5,9%) apresentou obstrução de via de saída de ventrículo esquerdo (VSVE), evoluindo para óbito logo após o procedimento, e outro morreu aos 161 dias de seguimento.Conclusão: A primeira experiência brasileira de TMVIV-transeptal demonstra a segurança e a efetividade dessa nova técnica. A obstrução da VSVE é uma complicação potencialmente fatal, reforçando a importância da seleção dos pacientes e do planejamento do procedimento. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0).

Second generation drug-eluting stents versus bare-metal stents for percutaneous coronary intervention of the proximal left anterior descending artery: An analysis of the BASKET-PROVE I and II trials.

OBJECTIVES: To compare mid-term outcomes between patients undergoing proximal left anterior descending artery (LAD) percutaneous coronary intervention (PCI) with second generation drug-eluting stent (DES) or bare-metal stent (BMS). BACKGROUND: PCI with BMS and first-generation DES have shown to be safe options for the treatment of proximal LAD stenosis, however associated with considerable reintervention rates. Overall, second-generation DES has proven to be superior to BMS and first-generation DES, nevertheless, its effect for proximal LAD PCI has not previously been reported. METHODS: We analyzed 2-year outcomes of 1,100 patients from the BASKET-PROVE I and II trials, referred for proximal LAD PCI with second generation DES (n = 680) or BMS (n = 420). RESULTS: The cumulative 2-year incidence of major adverse cardiac events (MACE, composite of cardiac death, myocardial infarction (MI) and target vessel revascularization (TVR)) was lower in second generation DES than in BMS treated patients (7.3% vs. 12.3%; HR 0.57, 95% CI 0.39/0.85), mainly driven by a reduced rate of TVR (3.7% vs. 10.0%; HR 0.35, CI 0.21/0.58). No difference was found in cardiac death (1.9% vs. 1.9%; HR 1.01, CI 0.42/2.44) and MI (4.4% vs. 4.7%; HR 0.93, CI 0.53/1.64). The benefit of DES use seemed to be more prominent in female patients with a reduction in MACE (P for interaction = 0.025). CONCLUSIONS: In patients with proximal LAD stenosis, treatment with second-generation DES was associated with reduced 2-year rates of adverse cardiac events and TVR compared to BMS, with reintervention rates similar to those earlier reported from bypass surgery.

Persistence and proliferation of human mesenchymal stromal cells in the right ventricular myocardium after intracoronary injection in a large animal model of pulmonary hypertension.

BACKGROUND AIMS: In this study, we demonstrate long-term persistence of human mesenchymal stromal cells (hMSCs) after intracoronary injection in a large animal model of pulmonary hypertension (PH). METHODS: Commercially available placenta-derived hMSCs were used. Experiments were conducted on 14 female Yorkshire swine. Four animals served as controls, and 10 underwent pulmonary vein (PV) banding. After 12 ± 2 weeks, PH and PV dysfunction were confirmed by right heart catheterization and cardiac magnetic resonance imaging. hMSCs were injected in the marginal branch of the right coronary artery. Tissues were harvested 6, 9 or 24 days after infusion. RESULTS: After 12 ± 2 weeks after PV banding, all subjects had increased mean pulmonary artery pressure (13.6 ± 3.6 versus 30.8 ± 4.5 mm Hg, P < 0.007) and a decrease in right ventricular ejection fraction from 51.7 ± 5.7% versus 30.5 ± 11.3% (P = 0.003). Intracoronary injection of hMSCs was well tolerated. Up to 24 days after hMSC injection, immunohistochemistry revealed extravascular viable human CD105+ mononuclear cells in the right ventricle (RV) that were Ki67+. This was confirmed by fluorescence in situ hybridization. CD45+ porcine inflammatory cells were identified, commonly seen adjacent to areas of healing microscopic infarction that likely dated to the time of the original hMSC injection. Anti-CD31 staining produced strong signals in areas of injected hMSCs. Immunohistochemistry staining for vascular cell adhesion molecule-1 showed upregulation in the clusters, where mononuclear cells were located. CONCLUSIONS: hMSCs injected via intracoronary infusion survived up to 24 days and demonstrated proliferative capacity. hMSCs can persist long term in the RV and are potential cell source for tissue repair in RV dysfunction.

Principais estudos clínicos sobre implante de válvula aórtica transcateter / Main clinical studies on transcatheter aortic valve implantation

A estenose aórtica (EA) é uma doença frequente na população idosa e, quando sintomática, tem prognóstico desfavorável, sendo recomendada nesta situação a substituição valvar cirúrgica. Embora o tratamento cirúrgico seja o padrão para a correção da EA muitos pacientes não são candidatos adequados, devido ao risco perioperatório muito elevado. O implante da valva aórtica transcateter (TAVI) surgiu como interessante alternativa, principalmente nos casos de pacientes inoperáveis, demonstrando melhora significativa na sobrevida com relação ao tratamento clínico. Nos pacientes com risco cirúrgico elevado apresentou resultados equivalentes à troca valvar aórtica cirúrgica, com taxas de sobrevivência equivalentes ou até superiores. Os resultados clínicos encorajadores somados aos rápidos avanços da tecnologia geraram interesse no uso desses dispositivos em pacientes de risco intermediário. Atualmente já existem evidências demonstrando a não inferioridade da TAVI com relação à cirurgia para a correção da EA em pacientes de médio risco e esses dispositivos já estão aprovados nos Estados Unidos e Europa para o tratamento desse grupo de pacientes. No presente artigo são sumarizados os principais estudos que foram fundamentais para a implementação da TAVI na prática clínica atual e para aprovação pelos principais órgãos reguladores mundiais

Aortic stenosis (AS) is a common disease in the elderly population; when symptomatic, it has an unfavorable prognosis and aortic valve replacement is recommended. Although surgical replacement is the standard treatment for AS, many patients are not suitable candidates because of high perioperative risk. Transcatheter aortic valve implantation (TAVI) has emerged as an interesting alternative, especially in inoperable cases, showing significant improvements in survival over clinical treatment. In patients with high surgical risk TAVI has demonstrated results equivalent to surgical aortic valve replacement with similar or even higher survival rates. These encouraging clinical results coupled with advances in technology have generated interest in using TAVI in lower-risk populations. There is currently evidence showing that TAVI is not inferior to surgical treatment of AS in intermediate-risk patients, and these devices have already been approved in the United States and Europe for treating this group of patients. This article summarizes the main studies that were fundamental in implementing TAVI into current clinical practice and approval by the main global regulatory agencies

Frequency of Cardiac Death and Stent Thrombosis in Patients With Chronic Obstructive Pulmonary Disease Undergoing Percutaneous Coronary Intervention (from the BASKET-PROVE I and II Trials).

Chronic obstructive pulmonary disease (COPD) is associated with long-term all-cause death after percutaneous coronary intervention with bare-metal stents. Regarding other outcomes, previous studies have shown conflicting results and the impact of drug-eluting stent (DES) in this population is not well known. We analyzed 4,605 patients who underwent percutaneous coronary intervention with bare-metal stents (33.1%) or DES (66.9%) from the Basel Stent Kosten-Effektivitats Trial-Prospective Validation Examination trials I and II. COPD patients (n = 283, 6.1%), were older and had more frequently a smoking or cardiovascular event history. At 2-year follow-up, cumulative event rates for patients with versus without COPD were the following: major adverse cardiac events (MACE: composite of cardiac death, nonfatal myocardial infarction, and target vessel revascularization): 15.2% versus 8.1% (p <0.001); all-cause death: 11.7% versus 2.4% (p <0.001); cardiac death: 5.7% versus 1.2% (p <0.001); myocardial infarction: 3.5% versus 1.9% (p = 0.045); definite/probable/possible stent thrombosis: 2.5% versus 0.9% (p = 0.01); and major bleeding: 4.2% versus 2.1% (p = 0.014). After adjusting for confounders including smoking status, COPD remained an independent predictor for MACE (hazard ratio [HR] 1.80, 95% confidence interval [CI] 1.31 to 2.49), all-cause death (HR 3.62, 95% CI 2.41 to 5.45), cardiac death (HR 3.12, 95% CI 1.74 to 5.60), and stent thrombosis (HR 2.39, 95% CI 1.03 to 5.54). We did not find evidence of an interaction between COPD and DES implantation (p for interaction = 0.29) for MACE. In conclusion, COPD is associated with increased 2-year rates of all-cause death, cardiac death, and stent thrombosis after stent implantation. DES use appears to be beneficial also in patients with COPD.

Stents farmacológicos de segunda geração para tratamento de lesões proximais isoladas da artéria descendente anterior. dados do registro Safira / Second-generation drug-eluting stent treatment for isolated proximal left anterior descending artery stenoses. the Safira registry data

Introdução: A estenose grave do terço proximal da artéria descendente anterior (ADA) é classificada como lesão de alto risco, visto que pode comprometer grande parte do miocárdio ventricular esquerdo. Os stents farmacológicos (SF) de segunda geração têm demonstrado maior eficácia e segurança quando comparados aos não farmacológicos ou aos de primeira geração. São escassos os relatos na literatura do emprego desses dispositivos para o tratamento de lesões isoladas do terço proximal da ADA. Métodos: Estudo observacional e prospectivo, que incluiu pacientes uniarteriais, portadores de lesão de novo no terço proximal da ADA, tratados eletivamente com SF de segunda geração. Avaliamos os desfechos clínicos hospitalares e tardios. Resultados: Foram incluídos 70 pacientes, sendo a maioria do sexo masculino (70%), com média de idades de 65,4 ± 11,2 anos e com alta prevalência de diabetes (37%). O quadro clínico mais frequente foi angina estável (57,1%) e metade das lesões era do tipo B2 ou C. Foram tratadas 70 lesões com 71 stents, com sucesso angiográfico de 100%. O desfecho primário composto por óbito cardíaco, infarto não fatal ou revascularização do vaso alvo no seguimento clínico de 2,5 anos ocorreu em 3% dos pacientes. A mortalidade cardíaca foi de 1,5%, e a revascularização da lesão alvo foi necessária em apenas 1,5% dos pacientes. Conclusões: Em pacientes uniarteriais com lesões de novo da ADA proximal, o tratamento eletivo com SF de segunda geração parece ser uma opção segura, com baixas taxas de eventos cardíacos adversos ou necessidade de nova revascularização

Background: Severe stenosis of the proximal left anterior descending artery (LAD) is classified as a high-risk lesion, as it may affect a large part of the left ventricular myocardium. Second-generation drug-eluting stents (DES) have been shown to be more effective and safer when compared to bare-metal or first-generation ones. There are few reports in the literature on the use of these devices for the treatment of isolated lesions in the proximal LAD. Methods: Observational and prospective study, which included single-vessel patients with de novo lesions in the proximal LAD, electively treated with second-generation DES. In-hospital and late clinical outcomes were evaluated. Results: Seventy patients were included, most of them males (70%), with a mean age of 65.4 ± 11.2 years and a high prevalence of diabetes (37%). The most common clinical presentation was stable angina (57.1%) and half of the lesions were type B2 or C. A total of 70 lesions were treated with 71 stents, with 100% angiographic success. The primary endpoint, consisting of cardiac death, nonfatal infarction, or target-vessel revascularization during the 2.5-year clinical follow-up, occurred in 3% of the patients. Cardiac death was 1.5%, and target-lesion revascularization was required in only 1.5% of the patients. Conclusions: Elective treatment with second-generation DES seems to be a safe option in single-vessel patients with de novo lesions in the proximal LAD, with low rates of adverse cardiac events or need for additional revascularization procedure