Intracoronary stem-cell injection after myocardial infarction: microcirculation sub-study.

BACKGROUND: The injection of stem cells in the context of acute myocardial infarction (AMI) has been tested almost exclusively by anterograde intra-arterial coronary (IAC) delivery. The retrograde intravenous coronary (IVC) delivery may be an additional route. OBJECTIVE: To compare the cell distribution and retention pattern in the anterograde and retrograde routes. To investigate the role of microvascular obstruction by magnetic resonance imaging in cell retention by cardiac tissue after the injection of bone marrow mononuclear cells (BMMC) in AMI. METHODS: This was a prospective, open label, randomized study. Patients with AMI who presented: (1) successful chemical or mechanical reperfusion within 24 hours of symptom onset and (2) infarction involving more than 10% of the left ventricle (LV) at the myocardial scintigraphy were included in the study. One hundred million BMMC were injected into the infarction-related artery through IAC route, or vein through the IVC route. One percent of the injected cells were labeled with 99mTc-hexamethyl-propylene-amine-oxime (99mTc-HMPAO). Cell distribution was evaluated at 4 and 24 hours after the myocardial scintigraphy injection. Cardiac magnetic resonance imaging was performed before cell injection. RESULTS: Thirty patients were randomized into three groups. There were no serious adverse events related to the procedure. The early and late retention of labeled cells was higher in the IAC group than in IVC group, regardless of the presence of microcirculation obstruction. CONCLUSION: The injection using the retrograde approach was feasible and safe. Cell retention by cardiac tissue was higher using the anterograde approach. More studies are needed to confirm these findings.

Injeção intracoronariana de células tronco após infarto do miocárdio: subestudo da microcirculação / Intracoronary stem-cell injection after myocardial infarction: microcirculation sub-study

FUNDAMENTO: A injeção de células-tronco no contexto do infarto agudo do miocárdio (IAM) tem sido testada quase exclusivamente pela via anterógrada intra-arterial coronariana (IAC). A via retrógrada intravenosa coronariana (IVC) pode ser uma via adicional. OBJETIVO: Comparar o padrão de distribuição e retenção celular nas vias anterógrada e retrógrada. Investigar o papel da obstrução microvascular pela ressonância magnética na retenção de células pelo tecido cardíaco após a injeção de células mononucleares da medula óssea (CMMO) no IAM. MÉTODOS: Estudo prospectivo, aberto, randomizado. Foram incluídos pacientes com IAM que apresentassem: (1) reperfusão mecânica ou química com sucesso em até 24 horas do início dos sintomas e (2) infarto acometendo mais de 10 por cento da área do ventrículo esquerdo (VE) pela cintilografia miocárdica. Cem milhões de CMMO foram injetadas na artéria relacionada ao infarto pela via IAC ou veia, pela via IVC. Um por cento das células injetadas foi marcado com Tc99m-hexametil-propileno-amina-oxima(99mTc-HMPAO). A distribuição das células foi avaliada 4 e 24 horas após a injeção da cintilografia miocárdica. Ressonância magnética cardíaca foi realizada antes da injeção de células. RESULTADOS: Trinta pacientes foram distribuídos aleatoriamente em três grupos. Não houve eventos adversos graves relacionados ao procedimento. A retenção precoce e tardia das células marcadas foi maior no grupo IAC do que no grupo IVC, independentemente da presença de obstrução da microcirculação. CONCLUSÃO: A injeção pela abordagem retrógrada mostrou-se viável e segura. A retenção de células pelo tecido cardíaco foi maior pela via anterógrada. Mais estudos são necessários para confirmar esses achados.

BACKGROUND: The injection of stem cells in the context of acute myocardial infarction (AMI) has been tested almost exclusively by anterograde intra-arterial coronary (IAC) delivery. The retrograde intravenous coronary (IVC) delivery may be an additional route. OBJECTIVE: To compare the cell distribution and retention pattern in the anterograde and retrograde routes. To investigate the role of microvascular obstruction by magnetic resonance imaging in cell retention by cardiac tissue after the injection of bone marrow mononuclear cells (BMMC) in AMI. METHODS: This was a prospective, open label, randomized study. Patients with AMI who presented: (1) successful chemical or mechanical reperfusion within 24 hours of symptom onset and (2) infarction involving more than 10 percent of the left ventricle (LV) at the myocardial scintigraphy were included in the study. One hundred million BMMC were injected into the infarction-related artery through IAC route, or vein through the IVC route. One percent of the injected cells were labeled with 99mTc-hexamethyl-propylene-amine-oxime (99mTc-HMPAO). Cell distribution was evaluated at 4 and 24 hours after the myocardial scintigraphy injection. Cardiac magnetic resonance imaging was performed before cell injection. RESULTS: Thirty patients were randomized into three groups. There were no serious adverse events related to the procedure. The early and late retention of labeled cells was higher in the IAC group than in IVC group, regardless of the presence of microcirculation obstruction. CONCLUSION: The injection using the retrograde approach was feasible and safe. Cell retention by cardiac tissue was higher using the anterograde approach. More studies are needed to confirm these findings.

Prevalence of induced ischemia by mental distress.

BACKGROUND: The myocardial radionuclide imaging with mental distress seems to induce ischemia through a particular physiopathology when compared to radionuclide imaging with physical or pharmacological distress. OBJECTIVE: To assess the prevalence of induced myocardial ischemia by mental distress in patients with thoracic pain and radionuclide imaging with normal conventional distress, with 99mTc-Sestamibi. METHODS: Twenty-two patients were admitted with thoracic pain at emergency or were referred to the nuclear medicine service of our institution, where myocardial radionuclide imaging of distress or rest without ischemic alterations was carried out. The patients were, then, invited to go through an additional phase with mental distress induced by color conflict (Strop Color Test) with the objective of detecting myocardial ischemia. Two cardiologists and nuclear physicians performed the blind analysis of perfusional data and consequent quantification through Summed Difference Score (SDS), punctuating the segments that were altered after mental distress and comparing it to the rest period image. The presence of myocardial ischemia was considered if SDS > or = 3. RESULTS: The prevalence of mental distress-induced myocardial ischemia was 40% (9 positive patients). Among the 22 studied patients, there were no statistical differences with regard to the number of risk factors, mental distress-induced hemodynamic alterations, usage of medications, presented symptoms, presence or absence of coronary disease and variations of ejection fraction and final systolic volume of Gated SPECT. CONCLUSION: In a selected sample of patients with thoracic pain and normal myocardial radionuclide imaging, the research of myocardial ischemia induced by mental distress through radionuclide imaging may be positive in up to 40% of cases.

Effects of short-term carvedilol on the cardiac sympathetic activity assessed by 123I-MIBG scintigraphy.

BACKGROUND: Autonomic alterations in heart failure are associated with an increase in morbimortality. Several noninvasive methods have been employed to evaluate the sympathetic function, including the Meta-Iodobenzylguanidine (123I-MIBG) scintigraphy imaging of the heart. OBJECTIVE: to evaluate the cardiac sympathetic activity through 123I-MIBG scintigraphy, before and after three months of carvedilol therapy in patients with heart failure and left ventricular ejection fraction (LVEF) < 45%. PATIENTS AND METHODS: Sixteen patients, aged 56.3 +/- 12.6 years (11 males), with a mean LVEF of 28% +/- 8% and no previous use of beta-blockers were recruited for the study. Images of the heart innervation were acquired with 123I-MIBG, and the serum levels of catecholamines (epinephrine, dopamine and norepinephrine) were measured; the radioisotope ventriculography (RIV) was performed before and after a three-month therapy with carvedilol. RESULTS: Patients' functional class showed improvement: before the treatment, 50% of the patients were FC II and 50% were FC III. After 3 months, 7 patients were FC I (43.8%) and 9 were FC II (56.2%), (p = 0.0001). The mean LVEF assessed by RIV increased from 29% to 33% (p = 0.017). There was no significant variation in cardiac adrenergic activity assessed by 123I-MIBG (early and late resting images and washout rate). No significant variation was observed regarding the measurement of catecholamines. CONCLUSION: The short-term treatment with carvedilol promoted the clinical and LVEF improvement. However, this was not associated to an improvement in the cardiac adrenergic activity, assessed by 123I-MIBG scintigraphy, as well as the measurement of circulating catecholamines.

Prevalência de isquemia induzida por estresse mental / Prevalence of induced ischemia by mental distress

FUNDAMENTOS: A cintilografia miocárdica com estresse mental parece induzir isquemia através de uma fisiopatologia particular quando comparada com a cintilografia, utilizando o estresse físico ou farmacológico. OBJETIVO: Avaliar a prevalência de isquemia miocárdica induzida por estresse mental, em pacientes com dor torácica e cintilografia com estresse convencional normal, utilizando 99mTc-Sestamibi. MÉTODOS: 22 PAcientes foram admitidos com dor torácica na emergência, ou foram encaminhados ambulatorialmente ao serviço de medicina nuclear da nossa instituição, onde realizaram cintilografia miocárdica de estresse e repouso sem alterações isquêmicas. Então, foram convidados a realizar uma fase adicional com indução de estresse mental através do conflito de cores (Stroop Color Test) com o objetivo de detectar isquemia miocárdica. Dois cardiologistas e médicos nucleares realizaram a análise cega dos dados perfusionais e consequente quantificação através do SDS (Summed Diference Score), pontuando os segmentos com alteração perfusional após o estresse mental e comparando com a imagem de repouso. A presença de isquemia miocárdica foi considerada com SDS > 3. RESULTADOS: A prevalência de isquemia miocárdica induzida por estresse mental foi de 40 por cento (9 pacientes positivos). Nos 22 pacientes estudados não houve diferença estatística quanto ao número de fatores de risco, alterações hemodinâmicas induzidas pelo estresse mental, uso de medicações, sintomas apresentados, presença ou ausência de doença coronariana e variações da fração de ejeção e volume sistólico final do Gated SPECT. CONCLUSÃO: EM Uma amostra selecionada de pacientes com dor torácica e cintilografia miocárdica convencional normal, a pesquisa de isquemia miocárdica induzida pelo estresse mental através de cintilografia pode ser positiva em até 40 por cento dos casos.

BACKGROUND: The myocardial radionuclide imaging with mental distress seems to induce ischemia through a particular physiopathology when compared to radionuclide imaging with physical or pharmacological distress. OBJECTIVE: To assess the prevalence of induced myocardial ischemia by mental distress in patients with thoracic pain and radionuclide imaging with normal conventional distress, with 99mTc-Sestamibi. METHODS: Twenty-two patients were admitted with thoracic pain at emergency or were referred to the nuclear medicine service of our institution, where myocardial radionuclide imaging of distress or rest without ischemic alterations was carried out. The patients were, then, invited to go through an additional phase with mental distress induced by color conflict (Strop Color Test) with the objective of detecting myocardial ischemia. Two cardiologists and nuclear physicians performed the blind analysis of perfusional data and consequent quantification through Summed Difference Score (SDS), punctuating the segments that were altered after mental distress and comparing it to the rest period image. The presence of myocardial ischemia was considered if SDS > 3. RESULTS: The prevalence of mental distress-induced myocardial ischemia was 40 percent (9 positive patients). Among the 22 studied patients, there were no statistical differences with regard to the number of risk factors, mental distress-induced hemodynamic alterations, usage of medications, presented symptoms, presence or absence of coronary disease and variations of ejection fraction and final systolic volume of Gated SPECT. CONCLUSION: In a selected sample of patients with thoracic pain and normal myocardial radionuclide imaging, the research of myocardial ischemia induced by mental distress through radionuclide imaging may be positive in up to 40 percent of cases.

Efeito do carvedilol a curto prazo na atividade simpática cardíaca pela cintilografia com 123I-MIBG / Effects of short-term carvedilol on the cardiac sympathetic activity assessed by 123I-MIBG scintigraphy

FUNDAMENTO: Alterações autonômicas na insuficiência cardíaca estão associadas a um aumento da morbimortalidade. Vários métodos não invasivos têm sido empregados para avaliar a função simpática, incluindo a imagem cardíaca com 123I-MIBG. OBJETIVO: Avaliar a atividade simpática cardíaca, por meio da cintilografia com 123I-MIBG, antes e após três meses de terapia com carvedilol em pacientes com insuficiência cardíaca com fração de ejeção do VE <45 por cento (FEVE). MÉTODOS: Foram recrutados para o estudo 16 pacientes, com idade média de 56,3 ± 12,6 anos (11 do sexo masculino), fração de ejeção média de 28 por cento ± 8 por cento e sem uso prévio de betabloqueadores. Realizaram-se imagens da inervação cardíaca com 123I-MIBG, determinando os níveis séricos de catecolaminas (epinefrina, dopamina e norepinefrina), e empreendeu-se a ventriculografia radionuclídica antes e após o uso de carvedilol por três meses. RESULTADOS: Houve melhora da classe funcional dos pacientes: antes do tratamento, metade se encontrava em CF II (50 por cento) e metade em CF III. Após 3 meses, 7 pacientes encontravam-se em CF I (43,8 por cento) e 9 em CF II (56,2 por cento), (p = 0,0001). A FEVE média avaliada pela ventriculografia radionuclídica aumentou de 29 por cento para 33 por cento (p = 0,017). Não houve variação significativa da atividade adrenérgica cardíaca avaliada pelo 123I-MIBG (imagem precoce, tardia e taxa de washout). Não foi observada variação significativa nas dosagens das catecolaminas. CONCLUSÃO: O tratamento em curto prazo com carvedilol promoveu a melhora clínica e da FEVE. Entretanto, não foi associado à melhora da atividade adrenérgica cardíaca pela cintilografia com 123I-MIBG, bem como da dosagem das catecolaminas circulantes.

BACKGROUND: Autonomic alterations in heart failure are associated with an increase in morbimortality. Several noninvasive methods have been employed to evaluate the sympathetic function, including the Meta-Iodobenzylguanidine (123I-MIBG) scintigraphy imaging of the heart. OBJECTIVE: to evaluate the cardiac sympathetic activity through 123I-MIBG scintigraphy, before and after three months of carvedilol therapy in patients with heart failure and left ventricular ejection fraction (LVEF) < 45 percent. PATIENTS AND METHODS: Sixteen patients, aged 56.3 ± 12.6 years (11 males), with a mean LVEF of 28 percent ± 8 percent and no previous use of beta-blockers were recruited for the study. Images of the heart innervation were acquired with 123I-MIBG, and the serum levels of catecholamines (epinephrine, dopamine and norepinephrine) were measured; the radioisotope ventriculography (RIV) was performed before and after a three-month therapy with carvedilol. RESULTS: Patients' functional class showed improvement: before the treatment, 50 percent of the patients were FC II and 50 percent were FC III. After 3 months, 7 patients were FC I (43.8 percent) and 9 were FC II (56.2 percent), (p = 0.0001). The mean LVEF assessed by RIV increased from 29 percent to 33 percent (p = 0.017). There was no significant variation in cardiac adrenergic activity assessed by 123I-MIBG (early and late resting images and washout rate). No significant variation was observed regarding the measurement of catecholamines. CONCLUSION: The short-term treatment with carvedilol promoted the clinical and LVEF improvement. However, this was not associated to an improvement in the cardiac adrenergic activity, assessed by 123I-MIBG scintigraphy, as well as the measurement of circulating catecholamines.

Systolic function of patients with myocardial infarction undergoing autologous bone marrow transplantation.

BACKGROUND: Several studies have been published on the effect of bone-marrow stem cells on the left ventricle when acting on post- acute myocardial infarction remodeling. However, the results have been controversial. OBJECTIVE: To carry out an echocardiographic analysis of the systolic function of patients with acute myocardial infarction after autologous mononuclear bone marrow cell transplantation (AMBMCT) as performed via the intracoronary and intravenous routes. METHODS: This is an open-label, prospective, randomized study. INCLUSION CRITERIA: patients admitted for ST-elevation acute myocardial infarction (MI) who had undergone mechanical or chemical reperfusion within 24 hours of the onset of symptoms and whose echocardiogram showed decreased segmental wall motion and fixed perfusion defect related to the culprit artery. Autologous bone marrow was aspirated from the posterior iliac crest under sedation and analgesia of the patients randomly assigned for the treatment group. After laboratory manipulation, intracoronary or intravenous injection of 100 x 106 mononuclear cells was performed. Echocardiography (Vivid 7) was used to assess ventricular function before and three and six months after cell infusion. RESULTS: A total of 30 patients were included, 14 in the arterial group (AG), 10 in the venous group (VG), and six in the control group (CG). No statistical difference was found between the groups for the echocardiographic parameters studied. CONCLUSION: Autologous mononuclear bone marrow cell transplantation did not improve the echocardiographic parameters of systolic function.

Função sistólica de pacientes com infarto miocárdico submetidos a transplante autólogo da medula óssea / Systolic function of patients with myocardial infarction undergoing autologous bone marrow transplantation

FUNDAMENTO: Diversos estudos foram publicados sobre a ação de células tronco da medula óssea no ventrículo esquerdo, ao atuarem no remodelamento pós-infarto agudo do miocárdio. Os resultados, no entanto, têm se mostrado controversos. OBJETIVO: Avaliar através do ecocardiograma a função sistólica de pacientes com infarto agudo do miocárdio após o Transplante Autólogo de Células Mononucleares da Medula Óssea (TACMMO) através de duas vias injeção: intracoronariana e intravenosa. MÉTODOS: Estudo aberto, prospectivo, randomizado. Foram incluídos pacientes admitidos por infarto agudo do miocárdio (IAM) com supradesnivelamento do segmento ST e submetidos à reperfusão mecânica ou química, dentro de 24 horas após o início dos sintomas, que apresentavam ao ecocardiograma redução da contratilidade segmentar e defeito fixo da perfusão relacionada à artéria culpada pelo IAM. A medula óssea autóloga foi aspirada da crista ilíaca posterior sob sedação e analgesia, nos pacientes randomizados para o grupo tratado. Após manipulação laboratorial, 100 milhões de células mononucleares foram injetadas por via intracoronariana ou intravenosa. Utilizamos o ecocardiograma (Vivid 7) para avaliar a função ventricular antes e após três e seis meses da infusão de células. RESULTADOS: Foram incluídos trinta pacientes, 14 no grupo arterial (GA), dez no grupo venoso (GV) e seis no grupo controle (GC). Não houve diferença estatística dos parâmetros ecocardiográficos estudados entre os grupos. CONCLUSÃO: O transplante autólogo de células mononucleares da medula óssea não demonstrou melhora dos parâmetros ecocardiográficos da função sistólica.

BACKGROUND: Several studies have been published on the effect of bone-marrow stem cells on the left ventricle when acting on post- acute myocardial infarction remodeling. However, the results have been controversial. OBJECTIVE: To carry out an echocardiographic analysis of the systolic function of patients with acute myocardial infarction after autologous mononuclear bone marrow cell transplantation (AMBMCT) as performed via the intracoronary and intravenous routes. METHODS: This is an open-label, prospective, randomized study. Inclusion criteria: patients admitted for ST-elevation acute myocardial infarction (MI) who had undergone mechanical or chemical reperfusion within 24 hours of the onset of symptoms and whose echocardiogram showed decreased segmental wall motion and fixed perfusion defect related to the culprit artery. Autologous bone marrow was aspirated from the posterior iliac crest under sedation and analgesia of the patients randomly assigned for the treatment group. After laboratory manipulation, intracoronary or intravenous injection of 100 x 106 mononuclear cells was performed. Echocardiography (Vivid 7) was used to assess ventricular function before and three and six months after cell infusion. RESULTS: A total of 30 patients were included, 14 in the arterial group (AG), 10 in the venous group (VG), and six in the control group (CG). No statistical difference was found between the groups for the echocardiographic parameters studied. CONCLUSION: Autologous mononuclear bone marrow cell transplantation did not improve the echocardiographic parameters of systolic function.

Ventricular function following coronary artery bypass grafting: comparison between gated SPECT and cardiac magnetic resonance imaging.

BACKGROUND: The assessment of left ventricular function may be impaired by the abnormal interventricular septal motion frequently found after coronary artery bypass grafting (CABG). Studies on the validation of gated SPECT as a tool for the assessment of left ventricular function in this patient group are scarce. OBJECTIVE: We investigated the agreement and correlation between left ventricular ejection fraction (LVEF), end-diastolic volume (EDV), and end-systolic volume (ESV) as obtained using electrocardiogram-gated myocardial perfusion scintigraphy (gated SPECT) and cardiac magnetic resonance imaging in 20 patients undergoing coronary artery bypass grafting. METHODS: Correlation was measured using Spearman's correlation coefficient (rho). Agreement was assessed using Bland-Altman analysis. RESULTS: A good correlation was found between gated SPECT and cardiac magnetic resonance imaging in patients after CABG with regard to left ventricular ejection fraction (rho = 0.85; p =0.0001), moderate correlation for end-diastolic volume (rho = 0.51; p = 0.02), and non-significant correlation for end-diastolic volume (rho = 0.13; p = 0.5). Agreement ranges for LVEF, ESV and EDV were: -20% to 12%; -38 to 54 ml and; -96 to 100 ml, respectively. CONCLUSION: A reliable correlation was found for left ventricular ejection fraction as obtained by gated SPECT and magnetic resonance imaging in patients undergoing CABG. For ventricular volumes, however, the correlation is not adequate.

Use of resting myocardial scintigraphy during chest pain to exclude diagnosis of acute myocardial infarction.

BACKGROUND: Images of myocardial perfusion taken during an episode of chest pain have been used for patients in the emergency department. OBJECTIVE: To evaluate the operating characteristics of 99mTc-Tetrofosmin scintigraphy during an episode of chest pain to exclude the diagnosis of acute myocardial infarction. METHODS: One hundred and eight patients admitted with chest pain, or up to four hours after the end of symptoms and nondiagnostic electrocardiogram, underwent resting scintigraphy and measurement of troponin I concentrations. Patients with a history of myocardial infarction (MI) were not excluded (24 patients). Troponin I concentrations were determined at admission and 6 hours later. Nuclear physicians performed a blind analysis of the images, and myocardial infarction was confirmed whenever troponin I level increase was three times that of the control. RESULTS: Resting perfusion image was abnormal in all 6 patients with MI. Only 1 patient had a normal image and increased troponin levels. Fifty-five patients had positive images without MI, and 46 patients had normal images and troponin levels. The prevalence of the disease was 6.5%. The sensitivity and specificity of the resting images during an episode of chest pain to diagnose MI was 85.7% and 45.5%, respectively. The negative predictive value was 97.7%. CONCLUSION: Patients undergoing chest pain protocol with SPECT showed an excellent negative predictive value to exclude diagnosis of myocardial infarction. These results suggest that resting perfusion image is an important tool at the chest pain unit.

Bases da terapia celular em cardiologia / Cell therapy in cardiology

O implante de células para o tratamento de doenças cardiovasculares encontra-se sob investigação em vários centros no mundo. Várias linhagens celulares, de células-tronco bem caracterizadas a frações contendo diferentes tipos de células, têm sido investigadas em modelos animais. Apesar dos avanços obtidos na última década, na área de ciência básica, com relação a esta nova modalidade terapêutica, diversas questões permanecem sem resposta. Pouco ainda se sabe sobre os mecanismos através dos quais a terapia celular possa gerar resultados efetivos. Adicionalmente, a melhor via para o transplante, o número total e a concentração de células, e o melhor tipo celular permanecem questões importantes, ainda sem definição. É fato de que diversas células da medula óssea exercem seus efeitos através de mecanismos parácrinos e de que existe um complexo mecanismo de interação, contato e liberação de sinais entre essas células e as outras populações celulares nos órgãos lesados. Atualmente, a maioria dos estudos em humanos se concentra em células de origem adulta e autóloga, em oposição ao uso de células de origem embrionária. Esta revisão analisa os principais ensaios clínicos que utilizaram células derivadas de medula óssea em quatro cardiopatias: doença arterial coronariana aguda e crônica, e nas cardiomiopatias chagásica e dilatada. Os resultados desses estudos demonstram que o procedimento é seguro e exequível, e potencialmente eficaz. Inquestionavelmente, mais estudos pré-clínicos e clínicos são necessários para acessar o real potencial benefício desse novo modelo terapêutico.

Cell transplantation for the treatment of cardiovascular diseases is being investigated in many centers throughout the world. Various cell lines, from well characterized stem cells to cell fractions containing different types of cells, have been investigated in animal models. Despite progress in the basic research of this new therapy obtained over the last decade, many questions remain unanswered. We still know very little about the mechanisms of action that may lead to positive results after cell therapy. Additionally, the best route for cell transplantation, the best number and concentration of cells and the best cell type for transplant remain important questions that are still undefined. It is a fact that many bone marrow cells exert their effects through paracrine mechanisms, and that a complex mechanism of interaction, contact and signal release exists between these cells and other cell populations in damaged organs. Currently the majority of human studies are focused on the use of adult and autologous cells in contrast to the use of embryonic cells. This review describes the main clinical trials that have been performed using bone marrow-derived cells in the setting of four distinct heart diseases: acute and chronic ischemic heart disease and chagasic and dilated cardiomyopathies. Results from these studies demonstrate the procedure to be safe and feasible, and potentially efficacious. Undoubtedly more pre-clinical and clinical studies are necessary to assess the real potential benefit of this new therapeutic model.

Função ventricular após cirurgia de revascularização: Gated SPECT comparado à ressonância cardíaca / Ventricular function following coronary artery bypass grafting: comparison between Gated SPECT and cardiac magnetic resonance imaging / Función ventricular tras cirugía de revascularización: Gated SPECT comparado a la resonancia cardiaca

Fundamento: A avaliação da função ventricular esquerda pode ser limitada pela movimentação anômala do septo interventricular, freqüentemente encontrada após cirurgia de revascularização miocárdica (CRM). A validação do Gated SPECT como ferramenta para avaliação da função ventricular nesse grupo de pacientes é escassa. Objetivo: Investigamos a concordância e a correlação entre a fração de ejeção do ventrículo esquerdo (FEVE), o volume diastólico final (VDF) e o volume sistólico final (VDF), obtidos pela cintilografia de perfusão miocárdica tomográfica sincronizada pelo eletrocardiograma (Gated SPECT), com os mesmos parâmetros medidos pela ressonância magnética cardíaca em 20 pacientes submetidos à revascularização miocárdica. Métodos: A correlação foi medida pelo coeficiente de correlação de Spearman (ρ), enquanto a concordância foi avaliada por meio da análise de Bland e Altman.Resultados: Houve uma correlação boa entre o Gated SPECT e a ressonância magnética cardíaca nos pacientes após CRM em relação à fração de ejeção do ventrículo esquerdo (ρ = 0,85; p = 0,0001), uma correlação moderada para o volume sistólico final (ρ = 0,51; p = 0,02) e uma correlação insignificante para o volume diastólico final (ρ = 0,13; p = 0,5). Os limites de concordância para FEVE, VSF e VDF foram: de -20% a 12%; de -38 a 54ml e de -96 a 100ml, respectivamente.Conclusão: A fração de ejeção do ventrículo esquerdo obtida pelo Gated SPECT correlaciona-se de modo confiável com a da ressonância magnética em pacientes submetidos à CRM. Os volumes ventriculares, entretanto, não apresentam uma correlação adequada.

Background: The assessment of left ventricular function may be impaired by the abnormal interventricular septal motion frequently found after coronary artery bypass grafting (CABG). Studies on the validation of gated SPECT as a tool for the assessment of left ventricular function in this patient group are scarce. Objective: We investigated the agreement and correlation between left ventricular ejection fraction (LVEF), end-diastolic volume (EDV), and end-systolic volume (ESV) as obtained using electrocardiogram-gated myocardial perfusion scintigraphy (gated SPECT) and cardiac magnetic resonance imaging in 20 patients undergoing coronary artery bypass grafting. Methods: Correlation was measured using Spearman’s correlation coefficient (ρ). Agreement was assessed using Bland-Altman analysis. Results: A good correlation was found between gated SPECT and cardiac magnetic resonance imaging in patients after CABG with regard to left ventricular ejection fraction (ρ = 0.85; p =0.0001), moderate correlation for end-diastolic volume (ρ = 0.51; p = 0.02), and non-significant correlation for end-diastolic volume (ρ = 0.13; p = 0.5). Agreement ranges for LVEF, ESV and EDV were: -20% to 12%; -38 to 54 ml and; -96 to 100 ml, respectively. Conclusion: A reliable correlation was found for left ventricular ejection fraction as obtained by gated SPECT and magnetic resonance imaging in patients undergoing CABG. For ventricular volumes, however, the correlation is not adequate.

Fundamento: La evaluación de la función ventricular izquierda puede limitarse por el movimiento anómalo del septo interventricular, frecuentemente encontrado tras cirugía de revascularización miocárdica (CRM). La validación del Gated SPECT como herramienta para evaluación de la función ventricular en ese grupo de pacientes es rara. Objetivo: Investigamos la concordancia y la correlación entre la fracción de eyección del ventrículo izquierdo (FEVI), el volumen diastólico final (VDF) y el volumen sistólico final (VSF), obtenidos con la centellografía de perfusión miocárdica tomográfica sincronizada por electrocardiograma (Gated SPECT), con iguales parámetros medidos por medio de resonancia magnética cardiaca en 20 pacientes sometidos a la revascularización miocárdica. Métodos: Se apuró la correlación mediante el coeficiente de correlación de Spearman (ρ), mientras que se evaluó la concordancia por medio del análisis de Bland y Altman. Resultados: Hubo una correlación positiva entre el Gated SPECT y la resonancia magnética cardiaca en los pacientes tras CRM, con relación a la fracción de eyección del ventrículo izquierdo (ρ = 0,85; p = 0,0001), una correlación moderada para el volumen sistólico final (ρ = 0,51; p = 0,02) y una correlación insignificante para el volumen diastólico final (ρ = 0,13; p = 0,5). Los límites de concordancia para FEVI, VSF y VDF fueron: del -20% al 12%; de -38 a 54ml y de -96 a 100ml, respectivamente. Conclusión: La fracción de eyección (FE) del ventrículo izquierdo obtenida por el Gated SPECT se correlaciona de modo confiable con la FE de la resonancia magnética, en pacientes sometidos a CRM. Los volúmenes ventriculares, sin embargo, no presentan una correlación adecuada.

Uso da cintilografia miocárdica em repouso durante dor torácica para descartar infarto agudo do miocárdio / Utilización de la centellografía miocárdica en reposo durante dolor torácico para descartar infarto agudo de miocardio / Use of resting myocardial scintigraphy during chest pain to exclude diagnosis of acute myocardial infarction

FUNDAMENTO: A imagem de perfusão miocárdica adquirida durante episódio de dor torácica tem sido utilizada nos pacientes na sala de emergência. OBJETIVO: Avaliar as características operacionais da cintilografia com 99mTc-Tetrofosmin durante episódio de dor torácica para descartar o diagnóstico de infarto agudo do miocárdio. MÉTODOS: 108 pacientes admitidos com dor torácica ou até quatro horas do término dos sintomas e eletrocardiograma não diagnostico realizaram cintilografia em repouso e dosagens de troponina I. Pacientes com passado de infarto do miocárdio (IM) não foram excluídos (24 pacientes). Troponina I foi dosada na admissão e seis horas após. Médicos nucleares realizaram análise cega das imagens. Infarto do miocárdio foi confirmado com elevação da troponina I maior que três vezes o controle. RESULTADOS: A imagem perfusional de repouso foi anormal em todos os seis pacientes com IM. Apenas um paciente apresentou imagem normal e elevação da troponina. Outros 55 pacientes obtiveram imagem positiva sem IM e 46 pacientes com imagens e troponinas normais. A prevalência da doença foi 6,5 por cento. A sensibilidade da imagem de repouso durante dor torácica para a evidência de IM foi 85,7 por cento e especificidade de 45,5 por cento. O valor preditivo negativo foi 97,7 por cento. CONCLUSÃO: Pacientes submetidos ao protocolo de dor torácica com cintilografia de perfusão miocárdica demonstraram um excelente valor preditivo negativo para afastar o diagnóstico de infarto do miocárdio. Estes resultados sugerem que a imagem de perfusão em repouso é uma ferramenta importante na unidade de dor torácica.

BACKGROUND: Images of myocardial perfusion taken during an episode of chest pain have been used for patients in the emergency department. OBJECTIVE: To evaluate the operating characteristics of 99mTc-Tetrofosmin scintigraphy during an episode of chest pain to exclude the diagnosis of acute myocardial infarction. METHODS: One hundred and eight patients admitted with chest pain, or up to four hours after the end of symptoms and nondiagnostic electrocardiogram, underwent resting scintigraphy and measurement of troponin I concentrations. Patients with a history of myocardial infarction (MI) were not excluded (24 patients). Troponin I concentrations were determined at admission and 6 hours later. Nuclear physicians performed a blind analysis of the images, and myocardial infarction was confirmed whenever troponin I level increase was three times that of the control. RESULTS: Resting perfusion image was abnormal in all 6 patients with MI. Only 1 patient had a normal image and increased troponin levels. Fifty-five patients had positive images without MI, and 46 patients had normal images and troponin levels. The prevalence of the disease was 6.5 percent. The sensitivity and specificity of the resting images during an episode of chest pain to diagnose MI was 85.7 percent and 45.5 percent, respectively. The negative predictive value was 97.7 percent. CONCLUSION: Patients undergoing chest pain protocol with SPECT showed an excellent negative predictive value to exclude diagnosis of myocardial infarction. These results suggest that resting perfusion image is an important tool at the chest pain unit.

FUNDAMENTO: La utilización en los pacientes de la imagen de perfusión miocárdica, adquirida durante episodio de dolor torácico, es frecuente en la sala de emergencia. OBJETIVO: Evaluar las características operacionales de la centellografía con 99mTc-Tetrofosmin, durante episodio de dolor torácico, para descartar el diagnóstico de infarto agudo de miocardio. MÉTODOS: Un total de 108 pacientes ingresados con dolor torácico, o hasta tras 4 horas del término de los síntomas, con electrocardiograma no diagnostico, realizaron centellografía en reposo y dosificaciones de troponina I. No se excluyeron a los pacientes con pasado de infarto de miocardio (IM) (24 pacientes). Se dosificó troponina I al ingreso y tras 6 horas del ingreso. Médicos nucleares realizaron análisis ciego de las imágenes. Se confirmó infarto de miocardio, con elevación de la troponina I mayor que tres veces el control. RESULTADOS: La imagen de perfusión en reposo se mostró anormal en todos los seis pacientes con IM. Sólo un paciente presentó imagen normal y elevación de la troponina. Otros 55 pacientes obtuvieron imagen positiva sin IM y 46 pacientes presentaron imágenes y troponinas normales. La prevalencia de la enfermedad fue de un 6,5 por ciento. Fue de un 85,7 por ciento la sensibilidad de la imagen de reposo durante dolor torácico para la evidencia de IM, y la especificidad de un 45,5 por ciento. El valor predictivo negativo fue de un 97,7 por ciento. CONCLUSIÓN: Pacientes sometidos al protocolo de dolor torácico con centellografía de perfusión miocárdica demostraron un excelente valor predictivo negativo para la exclusión del diagnóstico de infarto de miocardio. Estos resultados sugieren que la imagen de perfusión en reposo es una herramienta importante en la unidad de dolor torácico.

Granulocyte-macrophage colony-stimulating factor gene based therapy for acute limb ischemia in a mouse model.

BACKGROUND: Granulocyte-colony-stimulating factor (GM-CSF) is a pleiotropic factor for hematopoiesis that stimulates myeloblasts, monoblasts and mobilization of bone marrow stem cells. Therefore, the GM-CSF gene is a potential candidate for vessel formation and tissue remodeling in the treatment of ischemic diseases. METHODS: A new mouse limb ischemia was established by surgery and gene transfer was performed by injection of 100 microg of a plasmid carrying GM-CSF. Muscle force and weight, histology, capillary density, circulating stem cells and monocytes were determined after 3-4 weeks. RESULTS: More than 60% of nontreated ischemic animals showed gangrene below the heel after 4 weeks, whereas the GM-CSF gene-treated animals showed only darkening of nails or toes. These animals demonstrated a full recovery of the affected muscles in terms of weight, force and muscle fiber structure, but the muscles of nontreated ischemic animals lost approximately 50% weight, 86% force and their regular structure. When the GM-CSF gene was injected into the contralateral limb, only partial loss was observed, demonstrating a distant effect of GM-CSF. The capillary density in the GM-CSF-treated group was 52% higher in relation to the nontreated group. Blood analysis by flow cytometry showed that the GM-CSF-treated group had 10-20% higher levels of circulating monocytes and Sca-1(+). CONCLUSIONS: We conclude that the direct administration of GM-CSF gene in limb ischemia had a strong therapeutic effect because it promoted the recovery of muscle mass, force and structure by mobilizing therapeutic cells and augmenting the number of vessels.

Correlation of myocardial interstitial collagen in the right ventricular septum with ventricular function of patients with ischemic cardiomyopathy.

BACKGROUND: Myocardial collagen content influences ventricular relaxation, contraction, and morphology. Its relationship with ventricular function in patients (Pts) with ischemic cardiomyopathy (ICMP) has not yet been fully studied in humans. OBJECTIVE: To assess the relationship between interstitial collagen content in non-infarcted areas of the right ventricular septum and ventricular function in ICMP. METHODS: 31 pts with coronary artery disease were divided into four groups as follows:The control group consisted of 7 pts with normal left (LVEF) and right (RVEF) ventricular ejection fraction (group C); Group 1: 5 patients with RVEF < 40%; Group 2: 9 pts with LVEF < 40%; and Group 3, 10 pts with biventricular dysfunction. RVEF and LVEF were measured by radionuclide angiography. For quantitative analysis of interstitial collagen volume fraction (CVF), endomyocardial biopsy specimens were taken from the right ventricle and stained with picrosirius red. RESULTS: Mean CVF was significantly higher in group 3, compared with the control group and with groups 1 and 2 (30.2 +/- 7.9% vs. 6.8 +/- 3.3% vs. 15.8 +/- 4.1% vs. 17.5+/-7.7%, respectively; p =0.0001). It was also significantly higher in patients belonging to group 2, compared with those in the control group (17.5 +/- 7.7% vs. 6.8 +/- 3.3%, p =0.0001). CVF was inversely correlated with RVEF (r = - 0.50, p = 0.003) and LVEF (r = -0.70, p = 0.0001). CONCLUSION: In ICMP, CVF is elevated in non-infarcted areas of the right ventricular septum and inversely correlated with right and left ventricular function.

Correlação do colágeno intersticial miocárdico do septo do ventrículo direito com a função ventricular em pacientes com cardiomiopatia isquêmica / Correlación del colágeno intersticial miocárdico del septo del ventrículo derecho con la función ventricular en pacientes con cardiomiopatía isquémica / Correlation of myocardial interstitial collagen in the right ventricular septum with ventricular function of patients with ischemic cardiomyopathy

FUNDAMENTO: O conteúdo de colágeno intersticial (CI) no miocárdio exerce influência no relaxamento e na contração ventricular. A sua relação com a função ventricular em pacientes (pcts) com cardiomiopatia isquêmica (CMPI) não está plenamente estudada em humanos. OBJETIVO: Avaliar a relação da quantidade de CI nas áreas não-infartadas no septo do ventrículo direito com a função ventricular na CMPI. MÉTODOS: 31pcts com doença arterial coronariana foram classificados em quatro grupos: Grupo C (Controle): 7pcts com as frações de ejeção dos ventrículos esquerdo (FEVE) e direito (FEVD) normais; Grupo 1: 5 pcts com FEVD < 40 por cento;Grupo 2: 9 pcts com FEVE < 40 por cento; Grupo 3: 10 pcts com disfunção de ambos os ventrículos. A FEVD e a FEVE foram calculadas por meio da angiocardiografia radionuclídica. As amostras para análise do por centoCI foram obtidas por meio de biópsia endomiocárdica do ventrículo direito e coradas pela técnica do picrosirius red. RESULTADOS: A média do por centoCI foi significativamente maior no grupo 3 quando comparada com o grupo-c e com os grupos 1 e 2 (30,2 ± 7,9 por cento vs. 6,8 ± 3,3 por cento vs. 15,8 ± 4,1 por cento vs. 17,5 ± 7,7 por cento, respectivamente; p = 0,0001). O por centoCI foi também significativamente maior nos pacientes do grupo 2 quando comparado com o controle(17,5 ± 7,7 por cento vs. 6,8 ± 3,3 por cento, p = 0.0001). O por centoCI apresentou correlação inversa com a FEVD (r = -0,50, p = 0.003) e FEVE (r = -0,70, p = 0,0001). CONCLUSÃO: Na CMPI, o por centoCI encontra-se elevado nas áreas não-infartadas no septo do ventrículo direito e apresenta correlação inversa com o a função ventricular direita e esquerda.

BACKGROUND: Myocardial collagen content influences ventricular relaxation, contraction, and morphology. Its relationship with ventricular function in patients (Pts) with ischemic cardiomyopathy (ICMP) has not yet been fully studied in humans. OBJECTIVE: To assess the relationship between interstitial collagen content in non-infarcted areas of the right ventricular septum and ventricular function in ICMP. METHODS: 31 pts with coronary artery disease were divided into four groups as follows:The control group consisted of 7 pts with normal left (LVEF) and right (RVEF) ventricular ejection fraction (group C); Group 1: 5 patients with RVEF < 40 percent; Group 2: 9 pts with LVEF < 40 percent; and Group 3, 10 pts with biventricular dysfunction. RVEF and LVEF were measured by radionuclide angiography. For quantitative analysis of interstitial collagen volume fraction (CVF), endomyocardial biopsy specimens were taken from the right ventricle and stained with picrosirius red. RESULTS: Mean CVF was significantly higher in group 3, compared with the control group and with groups 1 and 2 (30.2 ± 7.9 percent vs. 6.8 ± 3.3 percent vs. 15.8 ± 4.1 percent vs. 17.5±7.7 percent, respectively; p =0.0001). It was also significantly higher in patients belonging to group 2, compared with those in the control group (17.5 ± 7.7 percent vs. 6.8 ± 3.3 percent, p =0.0001). CVF was inversely correlated with RVEF (r = - 0.50, p = 0.003) and LVEF (r = -0.70, p = 0.0001). CONCLUSION: In ICMP, CVF is elevated in non-infarcted areas of the right ventricular septum and inversely correlated with right and left ventricular function.

FUNDAMENTO: El contenido de colágeno intersticial (CI) en el miocardio ejerce influencia en la relajación y en la contracción ventricular. Su relación con la función ventricular en pacientes (pcts) con cardiomiopatía isquémica (CMPI) no está plenamente estudiada en humanos. OBJETIVO: Evaluar la relación de la cantidad de CI en las áreas no infartadas en el septo del ventrículo derecho con la función ventricular en la CMPI. MÉTODOS: Se clasificaron a 31 pcts con enfermedad arterial coronaria en cuatro grupos: Grupo C (Control): 7 pcts con fracción de eyección de los ventrículos izquierdo (FEVI) y derecho (FEVD) normales; Grupo 1:5 pcts con FEVD < 40 por ciento; Grupo 2:9 pcts con FEVI < 40 por ciento; Grupo 3:10 pcts con disfunción de ambos los ventrículos. La FEVD y la FEVI se calcularon por medio de la angiocardiografía con radionúclidos. Las muestras para análisis del porcentaje de colágeno intersticial ( por cientoCI) se obtuvieron mediante biopsia endomiocárdica del ventrículo derecho y se colorearon con la técnica del picrosirius red. RESULTADOS: El promedio del por cientoCI fue significativamente mayor en el grupo 3 cuando comparado al grupo-c y a los grupos 1 y 2 (30,2 ± 7,9 por ciento vs. 6,8 ± 3,3 por ciento vs. 15,8 ± 4,1 por ciento vs. 17,5 ± 7,7 por ciento, respectivamente; p = 0,0001). El por cientoCI fue asimismo significativamente mayor en los pacientes del grupo 2 cuando comparado al control (17,5 ± 7,7 por ciento vs. 6,8 ± 3,3 por ciento, p = 0.0001). El por cientoCI presentó correlación inversa con la FEVD (r = -0,50, p = 0.003) y la FEVI (r = -0,70, p = 0,0001). CONCLUSIÓN: En la CMPI, el por cientoCI se encuentra elevado en las áreas no infartadas en el septo del ventrículo derecho y presenta correlación inversa con la función ventricular derecha e izquierda.

Infarto agudo do miocárdio: síndrome coronária aguda com supradesnivelamento do segmento ST - parte 2 / Acute myocardial infarction: ST elevation acute coronary syndrome: part 2

O infarto agudo do miocárdio (IAM) é uma das principais causas de mortalidade em todo o mundo. A incidência de morte por IAM era alta na década de 50. Com o surgimento das unidades de tratamento intensivo e das unidades coronarianas, essa mortalidade foi reduzida pela metade. Na década de 80 - com o início da recanalização da artéria coronária relacionada ao IAM, através do uso de fibrinolítico ou dos novos processos de intervenção percutânea - houve queda na incidência de óbitos de 6 por cento a 10 por cento. O presente artigo visa demonstrar os principais aspectos do tratamento do IAM.

Acute myocardial infarction (AMI) is a leading cause of mortality worldwide. The mortality rate for AMI had high incidence in the 50's, with the emergence of intensive Care Units and Coronary Units, mortality was reduced by half. In the 80's the early recanalization of coronary artery related to the AMI with the use of fibrinolytic and new procedures for percutaneous intervention, there was a decrease in the incidence of deaths in patients from 6 percent to 10 percent. This article aims to demonstrate the main aspects of the treatment of AMI.

Curso de atualização em cardiologia: aula 10. Miocardite como modelo de doença imunológica: aspectos clínicos e diagnósticos / Cardiology updating course: class 10. Miocardite as model of disease imunológica: clinical aspects and diagnoses

Miocardites são um grupo de doenças heterogêneas que podem ser compreendidas com uma fisiopatologia imunológica. Os autores discutem aspectos históricos e a imunologia dessas doenças, correlacionando o trabalho de cientistas como Carlos Chagas, Noel Rose e Nelson Vaz. Levam em consideração a evolução histórica do conhecimento científico e a mudança de paradigma em andamento na imunologia. Também analisam as principais manifestações clínicas e estratégias para o diagnóstico e abordam novas propostas para investigação clínica dessas síndromes.