Yeong-Hoon Choi

Impact of preoperative statin therapy on adverse postoperative outcomes in patients undergoing cardiac surgery: a meta-analysis of over 30 000 patients

AIMS To determine the strength of evidence for preoperative statin use for prevention of adverse postoperative outcomes in patients undergoing cardiac surgery. METHODS AND RESULTS After literature search in major databases, 19 studies were identified [three RCT (randomized prospective clinical trials), 16 observational] that reported outcomes of 31 725 cardiac surgery patients with (n = 17 201; 54%) or without (n = 14 524; 46%) preoperative statin therapy. Outcomes that were analysed included early all-cause mortality (30-day mortality), myocardial infarction (MI), atrial fibrillation (AF), stroke and renal failure. Odds ratio (OR) with 95% confidence intervals (95%CI) were reported using fixed or random effect models and publication bias was assessed. Preoperative statin therapy resulted in a 1.5% absolute risk reduction (2.2 vs. 3.7%; P < 0.0001) and 43% odds reduction for early all-cause mortality (OR 0.57; 95%CI: 0.49-0.67). A significant reduction (P < 0.01) in statin pretreated patients was also observed for AF (24.9 vs. 29.3%; OR 0.67, 95%CI: 0.51-0.88), stroke (2.1 vs. 2.9%, OR 0.74, 95%CI: 0.60-0.91), but not for MI (OR 1.11; 95%CI: 0.93-1.33) or renal failure (OR 0.78, 95%CI: 0.46-1.31). Funnel plot and Eggers regression analysis (P = 0.60) excluded relevant publication bias. CONCLUSION Our meta-analysis provides evidence that preoperative statin therapy exerts substantial clinical benefit on early postoperative adverse outcomes in cardiac surgery patients, but underscores the need for RCT trials.

Statins for prevention of atrial fibrillation after cardiac surgery: a systematic literature review

OBJECTIVE To determine the strength of evidence of preoperative statin therapy for prevention of atrial fibrillation after cardiac surgery. METHODS A meta-analysis was performed of randomized controlled trials and observational trials reporting the impact of preoperative statin therapy on the incidence of any type and new-onset atrial fibrillation after cardiac surgery. Unadjusted and adjusted treatment effects (odds ratio, 95% confidence intervals) were pooled using a random-effects model, and publication bias was assessed. RESULTS Thirteen studies were identified (3 randomized controlled trials, 10 observational trials) that reported the incidence of postoperative atrial fibrillation in 17,643 patients having cardiac surgery with (n = 10,304; 58%) or without (n = 7339; 42%) preoperative statin use. New-onset atrial fibrillation was reported in a total of 7855 patients. Postoperative incidence rates for any or new-onset atrial fibrillation were 24.6% and 29.9%, respectively. Preoperative statin use resulted in a 22% and 34% unadjusted odds reduction for any atrial fibrillation (odds ratio, 0.78; 95% confidence interval, 0.67-0.90) or new-onset atrial fibrillation (odds ratio, 0.66; 95% confidence interval, 0.51-0.84) after surgery (P < .001). Relevant publication bias and an unequal distribution of confounding variables favoring patients treated with statins were identified. Nevertheless, the beneficial actions of statins on atrial fibrillation persisted after pooled analysis of risk-adjusted treatment effects from randomized controlled trials and observational trials (any atrial fibrillation-odds ratio, 0.64; 95% confidence interval, 0.48-0.87; new-onset atrial fibrillation-odds ratio, 0.66; 95% confidence intervals, 0.48-0.89; P < .01). CONCLUSION Our meta-analysis provides evidence that preoperative statin therapy is associated with a reduction in the incidence of atrial fibrillation after cardiac surgery.

Combined characterization of microRNA and mRNA profiles delineates early differentiation pathways of CD133+ and CD34+ hematopoietic stem and progenitor cells.

MicroRNAs (miRNAs) have been shown to play an important role in hematopoiesis. To elucidate the role of miRNAs in the early steps of hematopoiesis, we directly compared donor‐matched CD133+ cells with the more differentiated CD34+CD133− and CD34−CD133− cells from bone marrow on the miRNA and mRNA level. Using quantitative whole genome miRNA microarray and sequencing‐based profiling, we found that between 109 (CD133+) and 216 (CD34−CD133−) miRNAs were expressed. Quantification revealed that the 25 highest expressed miRNAs accounted for 73% of the total miRNA pool. miR‐142‐3p was the highest expressed miRNA with up to 2,000 copies per cell in CD34+CD133− cells. Eighteen miRNAs were significantly differentially expressed between CD133+ and CD34+CD133− cells. We analyzed their biological role by examining the coexpression of miRNAs and its bioinformatically predicted mRNA targets and luciferase‐based reporter assays. We provide the first evidence for a direct regulation of CD133 by miR‐142‐3p as well as tropomyosin 1 and frizzled homolog 5 by miR‐29a. Overexpression of miRNAs in CD133+ cells demonstrated that miR‐142‐3p has a negative influence on the overall colony‐forming ability. In conclusion, the miRNAs expressed differentially between the CD133+ and CD34+CD133− cells are involved in inhibition of differentiation, prevention of apoptosis, and cytoskeletal remodeling. These results are highly relevant for stem cell‐based therapies with CD133+ cells and delineate for the first time how the stem cell character of CD133+ cells is defined by the expression of specific miRNAs. STEM CELLS 2011;29:847–857

Preoperative statin therapy in cardiac surgery: a meta-analysis of 90 000 patients †

The objective of this systematic literature review with meta-analysis was to determine the strength of evidence for a preoperative statin on the reduction of adverse postoperative outcomes in patients undergoing cardiac surgery. Randomized controlled (RCT) and observational trials were searched in online databases that reported about the effects of preoperative statin therapy on major adverse clinical outcomes after cardiac surgery. Analysed outcomes included early all-cause mortality, myocardial infarction, atrial fibrillation (AF), stroke and renal failure using a priori-defined criteria. Effect estimates were calculated and are given as odds ratio (OR) with 95% confidence intervals (95% CI) using fixed- or random-effect models. Literature search of all major databases retrieved 2371 studies. After screening, a total of 54 trials were identified (12 RCT, 42 observational) that reported outcomes of 91 491 cardiac surgery patients with (n = 46 614; 51%) or without (n = 44 877; 49%) preoperative statin therapy. Preoperative statin use resulted in a 0.9% absolute risk (2.6 vs 3.5%) and a 31% odds reduction for early all-cause mortality (OR 0.69; 95% CI 0.59-0.81; P < 0.0001). In addition, statin treatment before surgery was associated with a substantial reduction (P < 0.01) in the postoperative end-points AF (OR 0.71; 95% CI 0.61-0.82), new-onset AF (OR 0.68; 95% CI 0.54-0.85), stroke (OR 0.83; 95% CI 0.74-0.93), stay on intensive care unit (weighted mean difference [WMD] -0.14; 95% CI -0.23 to -0.03; P < 0.01) and in-hospital stay (WMD -0.57; 95% CI -0.76 to -0.38; P < 0.01). No statistical differences were found between groups with regard to myocardial infarction or renal failure. In conclusion, the current systematic review strengthens the evidence that preoperative statin therapy extends substantial clinical benefit to early postoperative outcomes in cardiac surgery patients.

Autologous CD133+ bone marrow cells and bypass grafting for regeneration of ischaemic myocardium: the Cardio133 trial

AIMS Intra-myocardial transplantation of CD133(+) bone marrow stem cells (BMC) yielded promising results in clinical pilot trials. We now performed the double-blinded, randomized, placebo-controlled CARDIO133 trial to determine its impact on left ventricular (LV) function and clinical symptoms. METHODS AND RESULTS Sixty patients with chronic ischaemic heart disease and impaired LV function (left ventricular ejection fraction, LVEF <35%) were randomized to undergo either coronary artery bypass grafting (CABG) and injection of CD133(+) BMC in the non-transmural, hypokinetic infarct border zone (CD133), or CABG and placebo injection (placebo). Pre-operative LVEF was 27 ± 6% in CD133 patients and 26 ± 6% in placebo patients. Outcome was assessed after 6 months, and the primary endpoint was LVEF measured by cardiac magnetic resonance imaging (MRI) at rest. The incidence of adverse events was similar in both groups. There was no difference in 6-min walking distance, Minnesota Living with Heart Failure score, or Canadian Cardiovascular Society (CCS) class between groups at follow-up, and New York Heart Association class improved more in the placebo group (P = 0.004). By cardiac MRI, LVEF at 6 months was 33 ± 8% in the placebo group and 31 ± 7% in verum patients (P = 0.3), with an average inter-group difference of -2.1% (95% CI -6.3 to 2.1). Systolic or diastolic LV dimensions at 6 months were not different, either. In the CD133 group, myocardial perfusion at rest recovered in more LV segments than in the placebo group (9 vs. 2%, P < 0.001). Scar mass decreased by 2.2 ± 5 g in CD133(+) patients (P = 0.05), but was unchanged in the placebo group (0.3 ± 4 g, P = 0.7; inter-group difference in change = 2 g (95% CI -1.1 to 5)). By speckle-tracking echocardiography, cell-treated patients showed a better recovery of regional wall motion when the target area was posterior. CONCLUSION Although there may be some improvements in scar size and regional perfusion, intra-myocardial injection of CD133(+) BMC has no effect on global LV function and clinical symptoms. Improvements in regional myocardial function are only detectable in patients with posterior infarction, probably because the interventricular septum after anterior infarction is not accessible by trans-epicardial injection. CLINICAL TRIAL REGISTRATION This trial was registered at http://www.clinicaltrials.gov under NCT00462774.

Current evidence of coronary artery bypass grafting off-pump versus on-pump: a systematic review with meta-analysis of over 16 900 patients investigated in randomized controlled trials†.

In the present systematic review with meta-analysis, we sought to determine the current strength of evidence for or against off-pump and on-pump coronary artery bypass grafting (CABG) with regard to hard clinical end-points, graft patency and cost-effectiveness. We performed a meta-analysis of only randomized controlled trials (RCT) which reported at least one of the desired end-points including: (i) major adverse cardiac and cerebrovascular events (MACCE), (ii) all-cause mortality, (iii) myocardial infarction, (iv) cerebrovascular accident, (v) repeat revascularization, (vi) graft patency and (vii) cost-effectiveness. The pooled treatment effects [odds ratio (OR) or weighted mean difference, 95% confidence intervals (95% CIs)] were assessed using a fixed or random effects model. A total of 16 904 patients from 51 studies were identified after literature search of the major databases using a predefined keyword list. The incidence of MACCE did not differ between the groups, neither during the first 30 days (OR: 0.93; 95% CI: 0.82-1.04) nor for the longest available follow-up (OR: 1.01; 95% CI: 0.92-1.12). While the incidence of mid-term graft failure (OR: 1.37; 95% CI: 1.09-1.72) and the need for repeat revascularization (OR: 1.55; 95% CI: 1.33-1.80) was increased after off-pump surgery, on-pump surgery was associated with an increased occurrence of stroke (OR: 0.74; 95% CI: 0.58-0.95), renal impairment (OR: 0.79; 95% CI: 0.71-0.89) and mediastinitis (OR: 0.44; 95% CI: 0.31-0.62). There was no difference with regard to hard clinical end-points between on- or off-pump surgery, including myocardial infarction or mortality. The present systematic review emphasizes that both off- and on-pump surgery provide excellent and comparable results in patients requiring surgical revascularization. The choice for either strategy should take into account the individual patient profile (comorbidities, life expectancy, etc.) and importantly, the surgeons experience in performing on- or off-pump CABG in their routine practice.

Time course of caspase activation in selectively vulnerable brain areas following global cerebral ischemia due to cardiac arrest in rats

This study evaluated the time course of caspase activation in selectively vulnerable brain areas (hippocampus, nucleus reticularis thalami (NRT), cortex and striatum) following cardiopulmonary resuscitation (CPR) after global cerebral ischemia due to cardiac arrest (CA) in rats. Caspases are well known to play a crucial role in the apoptotic cascade and inflammatory syndromes and, therefore, represent potential therapeutic postischemic targets. Given the delayed neurodegeneration following CA, it is highly important to study the time course of caspase activation in regard to therapeutic interventions after CA. To assess caspase activity, in situ staining was applied to detect general caspase activity at 6h, 3d and 7d and caspase-3 activity at 3d after return of spontaneous circulation (ROSC). For detection of neuronal apoptosis, TUNEL staining was applied at 7d after ROSC. Distinct patterns of early caspase activation were observed at 6h and 3d in the NRT and striatum and of late activation at 7d in the hippocampal CA-1 sector. General caspase and caspase-3 activity correlated strongly at 3d after ROSC in all areas studied. At 7d, the TUNEL-positive neuron counts in the hippocampal CA-1 sector correlated strongly with caspase activation. In conclusion, general caspase and caspase-3 activity after 6 min of CA and the delayed occurrence of TUNEL-positive neurons strongly indicate that neuronal degeneration after CA is at least strongly associated with apoptosis. Therefore, postischemic antiapoptotic interventions might offer potential future therapeutic opportunities global cerebral ischemia due to CA.

Outcomes after peripheral extracorporeal membrane oxygenation therapy for postcardiotomy cardiogenic shock: a single-center experience

BACKGROUND We assessed the short-term outcomes and predictors of 30-d mortality in patients requiring temporary, peripheral extracorporeal membrane oxygenation (ECMO) for postcardiotomy cardiac failure. METHODS The data were retrospectively obtained using our institutional patient database. All patients who had received peripheral ECMO support after surgery for acquired heart disease from 2006 to 2010 were included in the present study. The demographic and perioperative variables of the 30-d survivors and nonsurvivors were compared using the chi-square and t-test, and multivariate logistic regression analysis was performed to identify the predictors of 30-d all-cause mortality. RESULTS A total of 77 patients with a mean age of 60 ± 13 years were included in the present analysis. Successful weaning from peripheral ECMO was achieved in 62% after 79 ± 57 h of ECMO support. The overall 30-d mortality rate was 70%, and mortality was reduced to 52% in the patients in whom ECMO support could be weaned successfully. Age (per year) at ECMO implantation was the only independent preoperative predictor of 30-d mortality (odds ratio 1.09, 95% confidence interval 1.03-1.15; P = 0.003). In addition, greater lactate levels after 24 h of ECMO therapy, a longer duration of ECMO support, and the presence of any ECMO-related or gastrointestinal complications were independent predictive factors for 30-d mortality (P < 0.05). CONCLUSIONS ECMO therapy provides a valuable therapeutic strategy for postcardiotomy myocardial failure but is still limited by high complication rates with fewer than 30% of patients discharged from the hospital. Patient age appears to be an essential preoperative predictor for mortality, and the blood lactate level is a relevant marker for the assessment of efficient ECMO support.

Cell Therapy for Heart Disease: Great Expectations, As Yet Unmet

Regenerative medicine is often touted as an achievement of the new millennium, but many approaches to improve health by stimulating the organisms own capacity for healing have existed for a long time. Some components of todays regenerative medicine, however, are indeed fundamentally new developments, and one of those is the concept of increasing the number of contractile cells in the heart to cure heart failure, either by stimulating intrinsic regeneration processes or by transplanting exogenous cells. The aim of this paper is to review the current status of some key aspects of cell therapy and obstacles to clinical translation.

The Impact of Intraaortic Balloon Counterpulsation on Bypass Graft Flow in Patients with Peripheral ECMO

Abstract  Objective: Numerous reports have been performed to investigate the hemodynamic effects of intraaortic balloon pumping (IABP) and nonpulsatile circulatory extracorporeal membrane oxygenation (ECMO), but studies on its impact on coronary artery bypass graft flow during concomitant use of IABP and ECMO are lacking. The aim of this study was to assess the impact of additional IABP support on the degree of blood flow increase in bypass grafts in high‐risk patients with nonpulsatile femoral venoarterial ECMO. Methods: In six emergency coronary artery bypass graft patients (mean age = 66.3 ± 2.1 years, gender = five males and one female, ejection fraction = 25.0 ± 3.0%) requiring mechanical circulatory support with ECMO hemodynamic parameters and bypass graft flows were measured with and without IABP counterpulsation. A transit time flowmeter was used for intraoperative graft flow and pulsatility index (PI) measurements. Patients provided their control values. Results: The average value of the mean arterial pressure recorded prior to IABP was 63.6 + 2.9 mmHg and during IABP support 67.8 + 2.9 mmHg (p < 0.0001). IABP augmented the mean bypass graft flow from 46.8 ± 9.6 mL/min to 56.4 ± 12.1 mL/min (p < 0.005), resulting in a 17% increase. The difference in the PI was not statistically significant (2.6 ± 0.2 with IABP, 2.6 ± 0.3 without IABP). Conclusions: We conclude that IABP‐induced pulsatility significantly improves coronary bypass graft flows during nonpulsatile peripheral ECMO.