Intramyocardial Injection of Autologous Bone Marrow Cells as an Adjunctive Therapy to Incomplete Myocardial Revascularization - Safety Issues

OBJECTIVES: To determine the safety of intramyocardial injection of autologous bone marrow cells in patients undergoing surgical myocardial revascularization (CABG) for severe coronary artery disease. INTRODUCTION: There is little data available regarding the safety profile of autologous bone marrow cells injected during surgical myocardial revascularization. Potential risks include arrythmias, fibrosis in the injected sites and growth of non-cardiac tissues. METHODS: Ten patients (eight men) were enrolled; they were 59&plusmn;5 years old with limiting angina and were non-optimal candidates for complete CABG. Bone marrow cells (1.3&plusmn;0.3x10(8)) were obtained prior to surgery, and the lymphomonocytic fraction (CD34+=1.8&plusmn;0.3%) was separated by density gradient centrifugation. During surgery, bone marrow cells were injected in non-grafted areas of ischemic myocardium. During the first year after surgery, the patients underwent laboratory tests, cardiac imaging, and 24-hour ECG monitoring. RESULTS: Injected segments: inferior (n=7), anterior (n=2), septal (n=1), apical (n=1), and lateral (n=1) walls. Except for a transient elevation of C-reactive protein at one month post-surgery (P=0.01), laboratory tests results were within normal ranges; neither complex arrhythmias nor structural abnormalities were detected during follow-up. There was a reduction in functional class of angina from 3.6&plusmn;0.8 (baseline) to 1.2&plusmn;0.4 (one year) (P<0.0001). Also, patients had a significant decrease in the ischemic score assessed by magnetic resonance, not only globally from 0.65&plusmn;0.14 (baseline) to 0.17&plusmn;0.05 (one year) (P=0.002), but also in the injected areas from 1.11&plusmn;0.20 (baseline) to 0.34&plusmn;0.13 (one year) (P=0.0009). CONCLUSIONS: Intramyocardial injection of bone marrow cells combined with CABG appears to be safe. Theoretical concerns with arrhythmias and/or structural abnormalities after cell therapy were not confirmed in this safety trial

Doença cardiovascular e fatores de risco cardiovascular em candidatos a transplante renal Cardiovascular disease and risk factors in candidates for renal transplantation

OBJETIVO: Determinar a prevalência de doença cardiovascular (DCV) e de fatores de risco tradicionais em portadores de insuficiência renal crônica em avaliação para inclusão em lista para transplante renal. MÉTODOS: Foram submetidos à avaliação clínica e exames complementares 195 pacientes com insuficiência renal crônica dialítica e comparados a grupo de 334 hipertensos pareados por idade. As equações de Framingham foram usadas para o cálculo do risco absoluto (RA); o risco relativo (RR) foi calculado tendo como referência o risco absoluto da coorte de baixo risco de Framingham. RESULTADOS: Do total, 37% apresentaram algum tipo de doença cardiovascular na avaliação inicial, sendo que arteriopatia obstrutiva (23%) foi a mais prevalente. Excluídos os pacientes com doença cardiovascular, em relação aos fatores de risco tradicionais, houve diferença significativa quanto à pressão arterial sistólica e colesterol total (maiores no grupo de hipertensos) e às prevalências de homens, diabetes e tabagismo, maiores no grupo de insuficiência renal crônica, que apresentou maior grau de hipertrofia ventricular esquerda, menor pressão arterial diastólica e menor prevalência de história familiar de doença cardiovascular e obesidade. O risco relativo para doença cardiovascular dos pacientes com insuficiência renal crônica foi mais elevado em relação à população controle de Framingham porém não diferiu da observada no grupo de hipertensos. CONCLUSÃO: Em candidatos a transplante renal é significativa a prevalência de doença cardiovascular e de fatores de risco tradicionais; as equações de Framingham não quantificam adequadamente o risco cardiovascular real e outros fatores de risco específicos desta população devem contribuir para o maior risco cardiovascular.<br>OBJECTIVE: To determine the prevalence of cardiovascular disease (CVD) and traditional risk factors in patients with chronic renal failure undergoing evaluation for inclusion on the renal transplantation list. METHODS: One hundred ninety-five patients with dialytic chronic renal failure underwent clinical evaluation and complementary tests and were compared with a group of 334 hypertensive patients paired for age. The Framingham equations were used for calculating the absolute risk (AR). The relative risk (RR) was calculated based on the absolute risk of the low-risk Framingham cohort. RESULTS: Thirty-seven percent of the patients had some sort of cardiovascular disease on the initial evaluation, peripheral vascular disease (23%) being the most prevalent. Patients with cardiovascular disease were excluded. Regarding traditional risk factors, a significant difference was observed in systolic blood pressure and total cholesterol (greater in the hypertensive group), and in the prevalence of men, diabetes, and smoking, which were greater in the chronic renal failure group. The latter had a greater degree of left ventricular hypertrophy, lower diastolic blood pressure, and a lower prevalence of familial history of cardiovascular disease and obesity. The relative risk for cardiovascular disease in patients with chronic renal failure was greater compared with that in the Framingham control population, but it did not differ from that observed in the group of hypertensive individuals. CONCLUSION: The prevalence of cardiovascular disease and traditional risk factors is high among candidates for renal transplantation; the Framingham equations do not adequately quantify the real cardiovascular risk, and other risk factors specific for that population should contribute for their greater cardiovascular risk

Terapia celular associada à revascularização transmiocárdica laser como proposta no tratamento da angina refratária Cell therapy plus transmyocardial laser revascularization: a proposed alternative procedure for refractory angina

OBJETIVO: É descrita uma proposição cirúrgica para o tratamento de pacientes com doença arterial coronária (DAC) terminal, não mais passíveis de revascularização miocárdica convencional. Constitui-se na revascularização transmiocárdica com raios laser (RTML), associada ao emprego de células progenitoras hematopoiéticas autólogas (CPH). MÉTODOS: Nove pacientes (oito homens), 65±5 anos, com as características supracitadas foram submetidos ao procedimento combinado. Além da avaliação clínica, o protocolo incluiu o estudo da perfusão miocárdica através da ressonância cardíaca (RMC) sob estresse farmacológico, antes e seis meses após a intervenção cirúrgica. Procedeuse à RMTL através de minitoracotomia esquerda e utilização de laser de CO2, com média de 11±3 tiros por paciente. As CPH foram obtidas por punção medular, seguindo-se sua injeção direta (1,9±0,3x10(8) células/paciente) em múltiplas áreas do miocárdio isquêmico. RESULTADOS: Não ocorreram óbitos ou complicações imediatas decorrentes dos procedimentos. Um paciente faleceu no segundo ano de pós-operatório, de causa não cardíaca (choque séptico). O seguimento clínico pós-operatório desses pacientes revelou redução significativa da classe funcional de angina de 3,7±0,2 para 1,3±0,2 (p<0,0001). Também se verificou redução estatística do índice isquêmico do ventrículo esquerdo (VE) avaliado pela RMC de 1,64±0,10 para 0,88±0,09 (p=0,01). CONCLUSÃO: A associação da terapia celular com a RTML demonstrou-se segura nessa experiência inicial. Caso confirmado esse sinergismo em estudos mais abrangentes, com melhora da angina e redução documentada da isquemia miocárdica, passamos a contar com uma nova possibilidade de tratamento alternativo para esse grave grupo de pacientes.<br>OBJECTIVE: We tested the hypothesis that TMLR combined with intramyocardial injection of BMC is safe, and may help increase the functional capacity of patient with refractory angina. METHODS: Nine patients (eight men), 65±5 years old, with refractory angina for multivessel disease and previous myocardial revascularization procedures (CABG/PCI), not candidates for another procedure due to the extension of the disease were enrolled. TMLR (11±3 laser drills) was performed via a limited thoracotomy using a CO2 Heart Laser System. BMC were obtained immediately prior to surgery, and the lymphomonocytic fraction separated by density gradient centrifugation. During surgery, 5mL containing approximately 1.9±0.3x10(8) BMC were delivered by multiple injections in the ischemic myocardium. Before (B) and 6 months (6M) after the procedure, patient underwent clinical evaluation and myocardial perfusion assessment by cardiac magnetic resonance imaging (MRI) during pharmacological stress with dypiridamole. RESULTS: No major complications or deaths occurred during the procedure. One patient died after 2 years (non cardiac cause).There was a reduction in the ischemic score as assessed by MRI from 1.64±0.10 (B) to 0.88±0.09 (6M) (P=0.01). Clinically, there was a reduction in functional class of angina from 3.7±0.2 (B) to 1.3±0.2 (6M) (P<0.0001). CONCLUSIONS: In this initial experience, the combined strategy of TMLR plus cell therapy appeared to be safe, and may have synergistically acted to reduce myocardial ischemia, with clinically relevant improvement in functional capacity. Provided these data are confirmed in a larger, randomized, controlled trial with longer follow-up, this strategy could be used as a novel therapeutic option for treating pt with refractory angina

Predictors of Arrhythmic Events Detected by Implantable Loop Recorders in Renal Transplant Candidates

AbstractBackground:The recording of arrhythmic events (AE) in renal transplant candidates (RTCs) undergoing dialysis is limited by conventional electrocardiography. However, continuous cardiac rhythm monitoring seems to be more appropriate due to automatic detection of arrhythmia, but this method has not been used.Objective:We aimed to investigate the incidence and predictors of AE in RTCs using an implantable loop recorder (ILR).Methods:A prospective observational study conducted from June 2009 to January 2011 included 100 consecutive ambulatory RTCs who underwent ILR and were followed-up for at least 1 year. Multivariate logistic regression was applied to define predictors of AE.Results:During a mean follow-up of 424 ± 127 days, AE could be detected in 98% of patients, and 92% had more than one type of arrhythmia, with most considered potentially not serious. Sustained atrial tachycardia and atrial fibrillation occurred in 7% and 13% of patients, respectively, and bradyarrhythmia and non-sustained or sustained ventricular tachycardia (VT) occurred in 25% and 57%, respectively. There were 18 deaths, of which 7 were sudden cardiac events: 3 bradyarrhythmias, 1 ventricular fibrillation, 1 myocardial infarction, and 2 undetermined. The presence of a long QTc (odds ratio [OR] = 7.28; 95% confidence interval [CI], 2.01–26.35; p = 0.002), and the duration of the PR interval (OR = 1.05; 95% CI, 1.02–1.08; p < 0.001) were independently associated with bradyarrhythmias. Left ventricular dilatation (LVD) was independently associated with non-sustained VT (OR = 2.83; 95% CI, 1.01–7.96; p = 0.041).Conclusions:In medium-term follow-up of RTCs, ILR helped detect a high incidence of AE, most of which did not have clinical relevance. The PR interval and presence of long QTc were predictive of bradyarrhythmias, whereas LVD was predictive of non-sustained VT