Oj Liakopoulos

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.

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.

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.

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.

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.

The influence of cardiovascular risk factors on bone marrow mesenchymal stromal cell fitness

BACKGROUND AIMS In the past, cell transplantation strategies for the treatment of heart failure have shown promising results in experimental and clinical studies. Bone marrow (BM)-derived stem cells represent the most frequently used cell population. Within this heterogeneous cell population, mesenchymal stromal cells (MSC) have been identified to induce therapeutic effects, mainly through paracrine mechanisms. Because of their low frequency in native tissues, in vitro cell culture expansion is mandatory prior to transplantation. We sought to identify patient-specific cardiovascular risk factors influencing the proliferative potential of MSC. METHODS BM aspirates from 51 patients undergoing elective cardiac surgery were analyzed for MSC frequency and cell culture expansion potential. Fibroblastic colony-forming units (CFU-F) were quantified for culture conditions applying autologous (AS) or fetal bovine serum (FBS) and different basic media. Univariate and multivariate analyzes were performed in order to determine the impact of patient-specific factors on CFU-F numbers. RESULTS Expanded MSC showed a specific immune phenotype and displayed adipogenic, chondrogeneic and osteogeneic differentiation potential. CFU-F numbers did not differ under AS or FBS supplementation. Elevated numbers of mononuclear cells, diabetes mellitus, steroid treatment, chronic obstructive pulmonary disease, renal failure, high euroSCORE and impaired left ventricular function were significant determinants for higher CFU-F numbers. CONCLUSIONS The impact of specific cardiovascular risk factors on MSC fitness could be determined. These results may help to establish patient profiling in order to identify patients suitable for autologous MSC transplantation, and might lead to the identification of disease-related mechanisms of stem cell activation.

Renal impairment and transapical aortic valve implantation: impact of contrast medium dose on kidney function and survival

OBJECTIVE Patients undergoing transapical aortic valve implantation (TA-AVI) are usually over 80 years old and have a high prevalence of chronic kidney disease. However, transcatheter valve therapies require the use of contrast injections with the risk of nephrotoxicity. The aim of this study was to evaluate post-operative kidney function and survival in patients with pre-existing renal impairment with regard to the amount of contrast media used during TA-AVI. METHODS From January 2008 to March 2011, 50 patients (52% females, mean age 80.7 ± 5.3 years) with a serum creatinine level of >1.3 mg/dl were investigated. Patients receiving a dose of <100 ml of a contrast agent (low-dose group, n = 24) were separated from those who received >100 ml of a contrast agent (high-dose group, n = 26). An acute contrast-induced nephropathy (CIN) was defined as a serum creatinine increase of 0.5 mg/dl or by >25% of a baseline value within 48 h from contrast medium administration. Patients in both groups had similar characteristics in terms of age, sex, body mass index and comorbidities. RESULTS The median pre-contrast creatinine was 1.67 (1.37-1.83) mg/dl in the low-dose group and 1.51 (1.26-1.98) mg/dl in the high-dose group (P = 0.76). The post-contrast creatinine at 48 h was 1.53 (1.33-2.05) and 2.29 (1.67-2.86) mg/dl in the groups receiving low- and high-dose contrast agents, respectively (P = 0.007). CIN occurred in 41.7% (n = 10) of patients in the low-dose contrast group and in 69.2% (n = 18) in the high-dose contrast group (P = 0.046). Haemodialysis is necessary for 16.7% of the low-dose group and 38.5% of the high-dose group (P = 0.12). Trends towards longer intensive care unit and hospital stay were seen in patients with an extensive use of contrast media [4.3 (2.5-6.5) vs. 5 (3-7.8) days and 12 (9-14.3) vs. 13 (9-18) days, P = 0.091 vs. P = 0.546, respectively]. Regarding death, 3-month and 3-year mortality were significantly higher in the high-dose group (8.3 vs. 30.8%, P = 0.036 and 25 vs. 61.5%, P = 0.004, respectively). CONCLUSIONS Our results indicate a possible association between higher CIN and mortality rate and the extensive use of contrast media during TA-AVI among high-risk patients with pre-existing renal impairment.

Meta-Analysis of Patients Taking Statins Before Revascularization and Aortic Valve Surgery

Statin intake before cardiac surgery is associated with favorable outcomes. We sought to analyze the evidence for statin pretreatment before isolated coronary artery bypass graft surgery and aortic valve replacement surgery. In this meta-analysis, we demonstrate beneficial results for the endpoints mortality, stroke, atrial fibrillation, and length of stay in hospital in 36,053 statin-pretreated coronary artery bypass graft surgery patients compared with control subjects retrieved from 32 studies, but fail to detect relevant advantages through preoperative statin therapy for 3,091 patients undergoing aortic valve replacement from four trials. Strict adherence to guidelines recommending statin treatment before CABG surgery is therefore mandatory.

Current Evidence for Perioperative Statins in Cardiac Surgery

Cardiac surgery improves life expectancy and quality of life for the constantly ageing population in developed countries. Mediated by their lipid-dependent and lipid-independent mechanisms, statins are sought to provide benefit with regard to better outcomes after cardiac surgery. Current guidelines recommend statin use in patients undergoing coronary artery bypass grafting, while less evidence is available for patients referred to heart valve surgery. Optimal selection of statin drug and dosage including perioperative timing of statin therapy remains largely unknown, but results of ongoing meta-analyses and future randomized trials will add important evidence to guide perioperative statin treatment of cardiac surgery patients.

Noninvasive in vivo tracking of mesenchymal stem cells and evaluation of cell therapeutic effects in a murine model using a clinical 3.0 T MRI

Cardiac cell therapy with mesenchymal stem cells (MSCs) represents a promising treatment approach for endstage heart failure. However, little is known about the underlying mechanisms and the fate of the transplanted cells. The objective of the presented work is to determine the feasibility of magnetic resonance imaging (MRI) and in vivo monitoring after transplantation into infarcted mouse hearts using a clinical 3.0 T MRI device. The labeling procedure of bone marrow-derived MSCs with micron-sized paramagnetic iron oxide particles (MPIOs) did not affect the viability of the cells and their cell type-defining properties when compared to unlabeled cells. Using a clinical 3.0 T MRI scanner equipped with a dedicated small animal solenoid coil, 105 labeled MSCs could be detected and localized in the mouse hearts for up to 4 weeks after intramyocardial transplantation. Weekly ECG-gated scans using T1-weighted sequences were performed, and left ventricular function was assessed. Histological analysis of hearts confirmed the survival of labeled MSCs in the target area up to 4 weeks after transplantation. In conclusion, in vivo tracking of labeled MSCs using a clinical 3.0 T MRI scanner is feasible. In combination with assessment of heart function, this technology allows the monitoring of the therapeutic efficacy of regenerative therapies in a small animal model.