Association Between Body Mass Index, Obesity, and Clinical Outcomes Following Coronary Artery Bypass Grafting in Brazil: An Analysis of One Year of Follow-up of BYPASS Registry Patients.

OBJECTIVE: To investigate the association between body mass index (BMI), obesity, clinical outcomes, and mortality following coronary artery bypass grafting (CABG) in Brazil using a large sample with one year of follow-up from the Brazilian Registry of Cardiovascular Surgeries in Adults (or BYPASS) Registry database. METHODS: A multicenter cohort-study enrolled 2,589 patients submitted to isolated CABG and divided them into normal weight (BMI 20.0-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2), and obesity (BMI > 30.0 kg/m2) groups. Inpatient postoperative outcomes included the most frequently described complications and events. Collected post-discharge outcomes included rehospitalization and mortality rates within 30 days, six months, and one year of follow-up. RESULTS: Sternal wound infections (SWI) rate was higher in obese compared to normal-weight patients (relative risk [RR]=5.89, 95% confidence interval [CI]=2.37-17.82; P=0.001). Rehospitalization rates in six months after discharge were higher in obesity and overweight groups than in normal weight group (χ=6.03, P=0.049); obese patients presented a 2.2-fold increase in the risk for rehospitalization within six months compared to normal-weight patients (RR=2.16, 95% CI=1.17-4.09; P=0.045). Postoperative complications and mortality rates did not differ among groups during time periods. CONCLUSION: Obesity increased the risk for SWI, leading to higher rehospitalization rates and need for surgical interventions within six months following CABG. Age, female sex, and diabetes were associated with a higher risk of mortality. The obesity paradox remains controversial since BMI may not be sufficient to assess postoperative risk in light of more complex and dynamic evaluations of body composition and physical fitness.

Early Six-Minute Walk Test May Predict Midterm Outcomes Following Coronary Artery Bypass Grafting.

OBJECTIVE: This study aims to investigate the ability of the six-minute walk distance (6MWD) as a prognostic marker for midterm clinical outcomes three months after coronary artery bypass grafting (CABG), to identify possible predictors of fall in 6MWD in the early postoperative period, and to establish the percentage fall in early postoperative 6MWD, considering the preoperative baseline as 100%. METHODS: A prospective cohort of patients undergoing elective CABG were included. The percentage fall in 6MWD was assessed by the difference between preoperative and postoperative day (POD) five. Clinical outcomes were evaluated three months after hospital discharge. RESULTS: There was a significant decrease in 6MWD on POD5 compared with preoperative baseline values (percentage fall of 32.5±16.5%, P<0.0001). Linear regression analysis showed an independent association of the percentage fall of 6MWD with cardiopulmonary bypass (CPB) and preoperative inspiratory muscle strength. Receiver operating characteristic curve analysis revealed that the best cutoff value of percentage fall in 6MWD to predict poorer clinical outcomes at three months was 34.6% (area under the curve = 0.82, sensitivity = 78.95%, specificity = 76.19%, P=0.0001). CONCLUSION: This study indicates that a cutoff value of 34.6% in percentage fall of 6MWD on POD5 was able to predict poorer clinical outcomes at three months of follow-up after CABG. Use of CPB and preoperative inspiratory muscle strength were independent predictors of percentage fall of 6MWD in the postoperative period. These findings further support the clinical application of 6MWD and propose an inpatient preventive strategy to guide clinical management over time.

COVID-19 in the Perioperative Period of Cardiovascular Surgery: the Brazilian Experience.

INTRODUCTION: We investigated the clinical course and outcomes of patients submitted to cardiovascular surgery in Brazil and who had developed symptoms/signs of coronavirus disease 2019 (COVID-19) in the perioperative period. METHODS: A retrospective multicenter study including 104 patients who were allocated in three groups according to time of positive real time reverse transcriptase-polymerase chain reaction (RT-PCR) for the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2): group 1, patients who underwent cardiac surgery > 10 days after positive RT-PCR; group 2, patients with a positive RT-PCR within 10 days before or after surgery; group 3, patients who presented positive RT-PCR > 10 days after surgery. The primary outcome was mortality and secondary outcomes were postoperative complications, intensive care unit (ICU) length of stay, and postoperative days of hospitalization. RESULTS: The three groups were similar with respect to age, the European System of Cardiac Operative Risk Evaluation score, and comorbidities, except hypertension. Postoperative complications and death were significantly higher in groups 2 and 3 than in group 1, and no significant difference between groups 2 and 3 was seen. Group 2 showed a high prevalence of surgery performed as an urgent procedure. Although no significant differences were observed in ICU length of stay, total postoperative hospitalization time was significantly higher in group 3 than in groups 1 and 2. CONCLUSION: COVID-19 affecting the postoperative period of patients who underwent cardiovascular surgery is associated with a higher rate of morbidity and mortality. Delaying procedures in RT-PCR-positive patients may help reduce risks of perioperative complications and death.

The Anaortic Technique with Bilateral Internal Thoracic Artery Grafting - Filling the Gap in Coronary Artery Bypass Surgery.

Coronary artery bypass grafting (CABG) has consolidated its role as the most effective procedure for treating patients with advanced atherosclerotic coronary artery disease, reducing the long-term risk of myocardial infarction and death compared to other therapies and relieving angina. Despite the recognized benefits afforded by surgical myocardial revascularization, a subset of higher-risk patients bears a more elevated risk of perioperative stroke. Stroke remains the drawback of conventional CABG and has been strongly linked to aortic manipulation (cannulation, cross-clamping, and side-biting clamping for the performance of proximal aortic anastomoses) and the use of cardiopulmonary bypass. Adoption of off-pump CABG (OPCAB) is demonstrated to lower the risk of perioperative stroke, as well as reducing the risk of short-term mortality, renal failure, atrial fibrillation, bleeding, and length of intensive care unit stay. However, increased risk persists owing to the need for the tangential ascending aorta clamping to construct the proximal anastomosis. The concept of anaortic (aorta no-touch) OPCAB (anOPCAB) stems from eliminating ascending aorta manipulation, virtually abolishing the risk of embolism caused by aortic wall debris into the brain circulation. The adoption of anOPCAB has been shown to further decrease the risk of postoperative stroke, especially in higher-risk patients, entailing a step forward and a refinement of outcomes provided by the primeval OPCAB technique. Therefore, anOPCAB has been the recommended technique in patients with cerebrovascular disease and/or calcification or atheromatous plaque in the ascending aorta and should be preferred in patients with high-risk factors for neurological damage and stroke.

Transcatheter procedures in structural heart disease: The surgeon stepping-in.

The seismic impact of transcatheter interventions is rocking the spectrum of structural heart disease (SHD) treatment, with the compelling and attractive appeal of minimally invasive procedures and fast-track discharge. The trend is relentless and continual innovation comes to our doors nearly on a daily basis. Litwinowicz and colleagues describe their trailblazing experience in 223 consecutive patients in whom they performed left atrial appendage occlusion via the percutaneous route. All interventions were performed by surgeons, who had undergone pretraining in a simulation model. Soon thereafter, they were able to achieve outcomes that were comparable with those obtained by experienced interventional cardiologists. The unique surgeons' training and skills in open-heart surgery make their contribution to perfection and safety of SHD treatment, which are potentially exceptional and distinctive. Extrapolating for the entire field of SHD, which is blossoming ahead, the message to be conveyed is that cardiac surgeons must be trained and embrace every aspect of SHD.

A Dedicated Stitch to Allow Early Safe Mobilization Avoiding Drain-Induced Heart Injury.

Placement of a mediastinal drain is a routine procedure following heart surgery. Postoperative bed rest is often imposed due to the fear of potential risk of drain displacement and cardiac injury. We developed an encapsulating stitch as a feasible, effective and low-cost technique, which does not require advanced surgical skills for placement. This simple, novel approach compartmentalizes the drain allowing for safe early mobilization following cardiac surgery.

Oxygen uptake on-kinetics during six-minute walk test predicts short-term outcomes after off-pump coronary artery bypass surgery.

PURPOSE: We aimed to investigate the ability of oxygen uptake kinetics to predict short-term outcomes after off-pump coronary artery bypass grafting. METHODS: Fifty-two patients aged 60.9 ± 7.8 years waiting for off-pump coronary artery bypass surgery were evaluated. The 6-min walk test distance was performed pre-operatively, while simultaneously using a portable cardiopulmonary testing device. The transition of oxygen uptake kinetics from rest to exercise was recorded to calculate oxygen uptake kinetics fitting a monoexponential regression model. Oxygen uptake at steady state, constant time, and mean response time corrected by work rate were analysed. Short-term clinical outcomes were evaluated during the early post-operative of off-pump coronary artery bypass surgery. RESULTS: Multivariate analysis showed body mass index, surgery time, and mean response time corrected by work rate as independent predictors for short-term outcomes. The optimal mean response time corrected by work rate cut-off to estimate short-term clinical outcomes was 1.51 × 10-3 min2/ml. Patients with slower mean response time corrected by work rate demonstrated higher rates of hypertension, diabetes, EuroSCOREII, left ventricular dysfunction, and impaired 6-min walk test parameters. The per cent-predicted distance threshold of 66% in the pre-operative was associated with delayed oxygen uptake kinetics. CONCLUSIONS: Pre-operative oxygen uptake kinetics during 6-min walk test predicts short-term clinical outcomes after off-pump coronary artery bypass surgery. From a clinically applicable perspective, a threshold of 66% of pre-operative predicted 6-min walk test distance indicated slower kinetics, which leads to longer intensive care unit and post-surgery hospital length of stay. Implications for rehabilitation Coronary artery bypass grafting is a treatment aimed to improve expectancy of life and prevent disability due to the disease progression; The use of pre-operative submaximal functional capacity test enabled the identification of patients with high risk of complications, where patients with delayed oxygen uptake kinetics exhibited worse short-term outcomes; Our findings suggest the importance of the rehabilitation in the pre-operative in order to "pre-habilitate" the patients to the surgical procedure; Faster oxygen uptake on-kinetics could be achieved by improving the oxidative capacity of muscles and cardiovascular conditioning through rehabilitation, adding better results following cardiac surgery.

Hemodynamic Changes During Heart Displacement in Aorta No-Touch Off-Pump Coronary Artery Bypass Surgery: A Pilot Study.

OBJECTIVE: To evaluate the sequential changes of hemodynamic and metabolic parameters in patients who underwent aorta no-touch off-pump coronary artery bypass surgery (OPCAB). METHODS: Prospective study involving twenty-seven consecutive patients who underwent aorta no-touch OPCAB. The FloTrac/PreSep/Vigileo™ system (Edwards Lifesciences) was used to continuously record heart rate (HR), mean arterial blood pressure (MABP), central venous pressure (CVP), continuous cardiac index (FCI), stroke volume (SV), stroke volume variation (SVV), and central venous oxygen saturation (ScvO2). The parameters were assessed 5 min before, during and 5 min after each anastomosis (left anterior descending [LAD], posterior descending [PD], obtuse marginal [OM] and diagonal [Dg]). Postoperative lactate was also evaluated. RESULTS: There was no significant change in HR and MABP for all anastomoses, except for MABP during PD grafting (-10.1±2.7 mmHg, P=0.03). There was a significant decrease in ScvO2 only during PD and OM anastomoses (-9.4±0.4, P=0.03; -4.4±0.4, P=0.02; respectively). CVP drop after PD manipulation was strongly associated with a higher lactate during the first hours after surgery (r=-0.82; P=0.001). These hemodynamic changes were transient and entirely recovered after the heart was returned to its anatomical position. No significant differences were observed in FCI, SVV, or the systemic vascular resistance index (SVRI) during all anastomoses, except for a drop in SVRI during PD grafting (-8.03±2.3, P=0.007). SV tended to decrease during the procedure in all territories, but with statistically significant drop only in PD and OM grafting (-10.4±1.2, P=0.02; -13.6±5.1, P=0.007; respectively). CONCLUSION: Heart displacement for performing aorta no-touch OPCAB is well tolerated, with transient and endurable hemodynamic variations.

Extended-time of Noninvasive Positive Pressure Ventilation Improves Tissue Perfusion after Coronary Artery Bypass Surgery: a Randomized Clinical Trial.

OBJECTIVE: To compare the effects of extended- versus short-time noninvasive positive pressure ventilation on pulmonary function, tissue perfusion, and clinical outcomes in the early postoperative period following coronary artery bypass surgery in patients with preserved left ventricular function. METHODS: Patients were randomized into two groups according to noninvasive positive pressure ventilation intensity: short-time noninvasive positive pressure ventilation n=20 (S-NPPV) and extended-time noninvasive positive pressure ventilation n=21 (E-NPPV). S-NPPV was applied for 60 minutes during immediate postoperative period and 10 minutes, twice daily, from postoperative days 1-5. E-NPPV was performed for at least six hours during immediate postoperative period and 60 minutes, twice daily, from postoperative days 1-5. As a primary outcome, tissue perfusion was determined by central venous oxygen saturation and blood lactate level measured after anesthetic induction, immediately after extubation and following noninvasive positive pressure ventilation protocols. As a secondary outcome, pulmonary function tests were performed preoperatively and in the postoperative days 1, 3, and 5; clinical outcomes were recorded. RESULTS: Significant drop in blood lactate levels and an improvement in central venous oxygen saturation values in the E-NPPV group were observed when compared with S-NPPV group after study protocol (P<0.01). The E-NPPV group presented higher preservation of postoperative pulmonary function as well as lower incidence of respiratory events and shorter postoperative hospital stay (P<0.05). CONCLUSION: Prophylactic E-NPPV administered in the early postoperative period of coronary artery bypass surgery resulted in greater improvements in tissue perfusion, pulmonary function and clinical outcomes than S-NPPV, in patients with preserved left ventricular function. TRIAL REGISTRATION: Brazilian Registry of Clinical trial - RBR7sqj78 - http://www.ensaiosclinicos.gov.br.

Extended-time of noninvasive positive pressure ventilation improves tissue perfusion after coronary artery bypass surgery: a randomized clinical trial

Abstract Objective: To compare the effects of extended- versus short-time noninvasive positive pressure ventilation on pulmonary function, tissue perfusion, and clinical outcomes in the early postoperative period following coronary artery bypass surgery in patients with preserved left ventricular function. Methods: Patients were randomized into two groups according to noninvasive positive pressure ventilation intensity: short-time noninvasive positive pressure ventilation n=20 (S-NPPV) and extended-time noninvasive positive pressure ventilation n=21 (E-NPPV). S-NPPV was applied for 60 minutes during immediate postoperative period and 10 minutes, twice daily, from postoperative days 1-5. E-NPPV was performed for at least six hours during immediate postoperative period and 60 minutes, twice daily, from postoperative days 1-5. As a primary outcome, tissue perfusion was determined by central venous oxygen saturation and blood lactate level measured after anesthetic induction, immediately after extubation and following noninvasive positive pressure ventilation protocols. As a secondary outcome, pulmonary function tests were performed preoperatively and in the postoperative days 1, 3, and 5; clinical outcomes were recorded. Results: Significant drop in blood lactate levels and an improvement in central venous oxygen saturation values in the E-NPPV group were observed when compared with S-NPPV group after study protocol (P<0.01). The E-NPPV group presented higher preservation of postoperative pulmonary function as well as lower incidence of respiratory events and shorter postoperative hospital stay (P<0.05). Conclusion: Prophylactic E-NPPV administered in the early postoperative period of coronary artery bypass surgery resulted in greater improvements in tissue perfusion, pulmonary function and clinical outcomes than S-NPPV, in patients with preserved left ventricular function. Trial Registration: Brazilian Registry of Clinical trial - RBR7sqj78 - http://www.ensaiosclinicos.gov.br

Early Open-Lung Ventilation Improves Clinical Outcomes in Patients with Left Cardiac Dysfunction Undergoing Off-Pump Coronary Artery Bypass: a Randomized Controlled Trial.

Objective: To compare pulmonary function, functional capacity and clinical outcomes amongst three groups of patients with left ventricular dysfunction following off-pump coronary artery bypass, namely: 1) conventional mechanical ventilation (CMV); 2) late open lung strategy (L-OLS); and 3) early open lung strategy (E-OLS). Methods: Sixty-one patients were randomized into 3 groups: 1) CMV (n=21); 2) L-OLS (n=20) initiated after intensive care unit arrival; and 3) E-OLS (n=20) initiated after intubation. Spirometry was performed at bedside on preoperative and postoperative days (PODs) 1, 3, and 5. Partial pressure of arterial oxygen (PaO2) and pulmonary shunt fraction were evaluated preoperatively and on POD1. The 6-minute walk test was applied on the day before the operation and on POD5. Results: Both the open lung groups demonstrated higher forced vital capacity and forced expiratory volume in 1 second on PODs 1, 3 and 5 when compared to the CMV group (P<0.05). The 6-minute walk test distance was more preserved, shunt fraction was lower, and PaO2 was higher in both open-lung groups (P<0.05). Open-lung groups had shorter intubation time and hospital stay and also fewer respiratory events (P<0.05). Key measures were significantly more favorable in the E-OLS group compared to the L-OLS group. Conclusion: Both OLSs (L-OLS and E-OLS) were able to promote higher preservation of pulmonary function, greater recovery of functional capacity and better clinical outcomes following off-pump coronary artery bypass when compared to conventional mechanical ventilation. However, in this group of patients with reduced left ventricular function, initiation of the OLS intra-operatively was found to be more beneficial and optimal when compared to OLS initiation after intensive care unit arrival.

Analysis of the Use of Extracorporeal Circulation on the In-Hospital Outcomes of Dialytic Patients Who Underwent Myocardial Revascularization Surgery.

BACKGROUND: Myocardial revascularization surgery is the best treatment for dyalitic patients with multivessel coronary disease. However, the procedure still has high morbidity and mortality. The use of extracorporeal circulation (ECC) can have a negative impact on the in-hospital outcomes of these patients. OBJECTIVES: To evaluate the differences between the techniques with ECC and without ECC during the in-hospital course of dialytic patients who underwent surgical myocardial revascularization. METHODS: Unicentric study on 102 consecutive, unselected dialytic patients, who underwent myocardial revascularization surgery in a tertiary university hospital from 2007 to 2014. RESULTS: Sixty-three patients underwent surgery with ECC and 39 without ECC. A high prevalence of cardiovascular risk factors was found in both groups, without statistically significant difference between them. The group "without ECC" had greater number of revascularizations (2.4 vs. 1.7; p <0.0001) and increased need for blood components (77.7% vs. 25.6%; p <0.0001) and inotropic support (82.5% vs 35.8%; p <0.0001). In the postoperative course, the group "without ECC" required less vasoactive drugs, (61.5% vs. 82.5%; p = 0.0340) and shorter time of mechanical ventilation (13.0 hours vs. 36,3 hours, p = 0.0217), had higher extubation rates in the operating room (58.9% vs. 23.8%, p = 0.0006), lower infection rates (7.6% vs. 28.5%; p = 0.0120), and shorter ICU stay (5.2 days vs. 8.1 days; p = 0.0054) as compared with the group with ECC surgery. No difference in mortality was found between the groups. CONCLUSION: Myocardial revascularization with ECC in patients on dialysis resulted in higher morbidity in the perioperative period in comparison with the procedure without ECC, with no difference in mortality though.

Long-Term and Sustained Therapeutic Results of a Specific Promonocyte Cell Formulation in Refractory Angina: ReACT(®) (Refractory Angina Cell Therapy) Clinical Update and Cost-Effective Analysis.

Mononuclear stem cells have been studied for their potential in myocardial ischemia. In our previous published article, ReACT(®) phase I/II clinical trial, our results suggest that a certain cell population, promonocytes, directly correlated with the perceived angiogenesis in refractory angina patients. This study is ReACT's clinical update, assessing long-term sustained efficacy. The ReACT phase IIA/B noncontrolled, open-label, clinical trial enrolled 14 patients with refractory angina and viable ischemic myocardium, without ventricular dysfunction, who were not suitable for myocardial revascularization. The procedure consisted of direct myocardial injection of a specific mononuclear cell formulation, with a certain percentage of promonocytes, in a single series of multiple injections (24-90; 0.2 ml each) into specific areas of the left ventricle. Primary endpoints were Canadian Cardiovascular Society Angina Classification (CCSAC) improvement at the 12-month follow-up and ischemic area reduction (scintigraphic analysis) at the 12-month follow-up, in correlation with ReACT's formulation. A recovery index (for patients with more than 1 year follow-up) was created to evaluate CCSAC over time, until April 2011. Almost all patients presented progressive improvement in CCSAC beginning 3 months (p=0.002) postprocedure, which was sustained at the 12-month follow-up (p=0.002), as well as objective myocardium ischemic area reduction at 6 months (decrease of 15%, p<0.024) and 12 months (decrease of 100%, p<0.004) The recovery index (n=10) showed that the patients were graded less than CCSAC 4 for 73.9 ± 24.2% over a median follow-up time of 46.8 months. After characterization, ReACT's promonocyte concentration suggested a positive correlation with CCSAC improvement (r=-0.575, p=0.082). Quality of life (SF-36 questionnaire) improved significantly in almost all domains. Cost-effectiveness analysis showed decrease in angina-related direct costs. Refractory angina patients presented a sustained long-term improvement in CCSAC and myocardium ischemic areas after the procedure. The long-term follow-up and strong improvement in quality of life reinforce effectiveness. Promonocytes may play a key role in myocardial neoangiogenesis. ReACT dramatically decreased direct costs.

Experimental Study and Early Clinical Application Of a Sutureless Aortic Bioprosthesis.

INTRODUCTION: The conventional aortic valve replacement is the treatment of choice for symptomatic severe aortic stenosis. Transcatheter technique is a viable alternative with promising results for inoperable patients. Sutureless bioprostheses have shown benefits in high-risk patients, such as reduction of aortic clamping and cardiopulmonary bypass, decreasing risks and adverse effects. OBJECTIVE: The objective of this study was to experimentally evaluate the implantation of a novel balloon-expandable aortic valve with sutureless bioprosthesis in sheep and report the early clinical application. METHODS: The bioprosthesis is made of a metal frame and bovine pericardium leaflets, encapsulated in a catheter. The animals underwent left thoracotomy and the cardiopulmonary bypass was established. The sutureless bioprosthesis was deployed to the aortic valve, with 1/3 of the structure on the left ventricular face. Cardiopulmonary bypass, aortic clamping and deployment times were recorded. Echocardiograms were performed before, during and after the surgery. The bioprosthesis was initially implanted in an 85 year-old patient with aortic stenosis and high risk for conventional surgery, EuroSCORE 40 and multiple comorbidities. RESULTS: The sutureless bioprosthesis was rapidly deployed (50-170 seconds; average=95 seconds). The aortic clamping time ranged from 6-10 minutes, average of 7 minutes; the mean cardiopulmonary bypass time was 71 minutes. Bioprostheses were properly positioned without perivalvar leak. In the first operated patient the aortic clamp time was 39 minutes and the patient had good postoperative course. CONCLUSION: The deployment of the sutureless bioprosthesis was safe and effective, thereby representing a new alternative to conventional surgery or transcatheter in moderate- to high-risk patients with severe aortic stenosis.

Paraplegia after off-pump coronary artery bypass grafting.

We report the case of a young patient who developed paraplegia after CABG without CPB. It is important to point out that this patient's aorta was not manipulated in any way because the only graft performed was a left internal mammary artery to left anterior descending artery.

Myocardial revascularization in dyalitic patients: in-hospital period evaluation.

BACKGROUND: Coronary artery bypass grafting currently is the best treatment for dialytic patients with multivessel coronary disease, but hospital morbidity and mortality related to procedure is still high. OBJECTIVE: Evaluate results and in-hospital outcomes of coronary artery bypass grafting in dialytic patients. METHODS: Retrospective unicentric study including 50 consecutive and not selected dialytic patients, who underwent coronary artery bypass grafting in a tertiary university hospital from 2007 to 2012. RESULTS: High prevalence of cardiovascular risk factors was observed (100% hypertensive, 68% diabetic and 40% dyslipidemic). There was no intra-operative death and 60% of the procedures were performed off-pump. There were seven (14%) in-hospital deaths. Postoperative infection, previous heart failure, cardiopulmonary bypass, abnormal ventricular function and surgical re-exploration were associated with increased mortality. CONCLUSION: Coronary artery bypass grafting is feasible to dialytic patients although high in-hospital morbidity and mortality. It is necessary better understanding about metabolic aspects to plan adequate interventions.

Monocyte transplantation for neural and cardiovascular ischemia repair.

Neovascularization is an integral process of inflammatory reactions and subsequent repair cascades in tissue injury. Monocytes/macrophages play a key role in the inflammatory process including angiogenesis as well as the defence mechanisms by exerting microbicidal and immunomodulatory activity. Current studies have demonstrated that recruited monocytes/macrophages aid in regulating angiogenesis in ischemic tissue, tumours and chronic inflammation. In terms of neovascularization followed by tissue regeneration, monocytes/macrophages should be highly attractive for cell-based therapy compared to any other stem cells due to their considerable advantages: non-oncogenic, non-teratogenic, multiple secretary functions including pro-angiogenic and growth factors, straightforward cell harvesting procedure and non-existent ethical controversy. In addition to adult origins such as bone marrow or peripheral blood, umbilical cord blood (UCB) can be a potential source for autologous or allogeneic monocytes/macrophages. Especially, UCB monocytes should be considered as the first candidate owing to their feasibility, low immune rejection and multiple characteristic advantages such as their anti-inflammatory properties by virtue of their unique immune and inflammatory immaturity, and their pro-angiogenic ability. In this review, we present general characteristics and potential of monocytes/macrophages for cell-based therapy, especially focusing on neovascularization and UCB-derived monocytes.

Refractory angina cell therapy (ReACT) involving autologous bone marrow cells in patients without left ventricular dysfunction: a possible role for monocytes.

Autologous bone marrow mononuclear cell (BMMC) transplantation has emerged as a potential therapeutic option for refractory angina patients. Previous studies have shown conflicting myocardium reperfusion results. The present study evaluated safety and efficacy of CellPraxis Refractory Angina Cell Therapy Protocol (ReACT), in which a specific BMMC formulation was administered as the sole therapy for these patients. The phase I/IIa noncontrolled, open label, clinical trial, involved eight patients with refractory angina and viable ischemic myocardium, without left ventricular dysfunction and who were not suitable for conventional myocardial revascularization. ReACT is a surgical procedure involving a single series of multiple injections (40-90 injections, 0.2 ml each) into ischemic areas of the left ventricle. Primary endpoints were Canadian Cardiovascular Society Angina Classification (CCSAC) improvement at 18 months follow-up and myocardium ischemic area reduction (assessed by scintigraphic analysis) at 12 months follow-up, in correlation with a specific BMMC formulation. Almost all patients presented progressive improvement in angina classification beginning 3 months (p = 0.008) postprocedure, which was sustained at 18 months follow-up (p = 0.004), as well as objective myocardium ischemic area reduction at 12 months (decrease of 84.4%, p < 0.004). A positive correlation was found between monocyte concentration and CCSAC improvement (r = -0.759, p < 0.05). Improvement in CCSAC, followed by correlated reduction in scintigraphic myocardium ischemic area, strongly suggests neoangiogenesis as the main stem cell action mechanism. The significant correlation between number of monocytes and improvement strongly supports a cell-related effect of ReACT. ReACT appeared safe and effective.