Shiju Zhang

MicroRNA: Novel Regulators Involved in the Remodeling and Reverse Remodeling of the Heart

Background: MicroRNAs (miRNAs) may serve as potential diagnostic biomarkers and therapeutic targets in cardiovascular research. However, the association between miRNAs and heart remodeling/reverse remodeling has not been evaluated. Methods: Lewis rats were divided into three groups: control animals, animals subjected to abdominal aortic constriction (AAC) and those with heterotopic transplantation of abdominal aortic constriction (AAC-HT), respectively. The cardiomyocyte cross-sectional area and changes in the heart cavity were determined. miRNA microarray was used to search for changes in miRNAs during hypertrophy and in the unloading heart, which was also verified using real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Results: The AAC-HT group exhibited a 54% decrease in the cardiomyocyte cross-sectional area compared to the AAC group. In the two test groups, miRNA microarrays revealed changes in 293 miRNAs, among which 40 miRNAs changed >2-fold. Some major changes were also confirmed using qRT-PCR primers. The results indicated that changes in miR-23a and miR-29a were most significant, thus suggesting that these miRNAs may play important roles in heart remodeling and reverse remodeling. Conclusions: The changes observed in miRNA expression during hypertrophy and reverse remodeling may indicate possibly meaningful targets for regulating the remodeling or reverse remodeling of the heart.

Comparison of Drug-Eluting Stents and Coronary Artery Bypass Surgery for the Treatment of Multivessel Coronary Disease Three-Year Follow-Up Results From a Single Institution

Background— Numerous studies have compared the outcomes of coronary artery bypass grafting (CABG) surgery and coronary stenting for the treatment of multivessel coronary disease. In 2003, drug-eluting stents were introduced with the hope of reducing restenosis. However, limited information exists on the comparison of drug-eluting stents and CABG surgery. The long-term outcome of drug-eluting stents compared with that of CABG surgery is also unclear. Methods and Results— We identified 3720 consecutive patients with multivessel disease who underwent isolated CABG surgery or received drug-eluting stents between April 1, 2004, and December 31, 2005, and we compared safety (total mortality, myocardial infarction, and stroke) and efficacy (target-vessel revascularization) during a 3-year follow-up. These outcomes were compared after adjustment for differences in baseline risk factors. Patients who underwent CABG (n=1886) were older and had more comorbidities than patients who received drug-eluting stents (n=1834). Patients receiving drug-eluting stents had considerably higher 3-year rates of target-vessel revascularization. Drug-eluting stents were also associated with higher rates of death (adjusted hazard ratio, 1.62; 95% confidence interval, 1.07 to 2.47) and myocardial infarction (adjusted hazard ratio, 1.65; 95% confidence interval, 1.15 to 2.44). The risk adjusted rate of stroke was similar in the 2 groups (hazard ratio, 0.92; 95% confidence interval, 0.69 to 1.51). Conclusions— In a cohort of patients with multivessel disease, CABG was associated with lower rates of death, myocardial infarction, and target-vessel revascularization than drug-eluting stents.

Impact of Off-Pump Techniques on Sex Differences in Early and Late Outcomes After Isolated Coronary Artery Bypass Grafts

BACKGROUND Off-pump coronary artery bypass graft surgery (OPCAB) is associated with lower early mortality and benefits women disproportionately. The objective of this study was to assess the impact of off-pump techniques on sex differences in late outcomes. METHODS We reviewed a clinical database of consecutive patients who underwent isolated coronary artery bypass graft surgery (CABG) at FuWai Hospital from 1999 to 2005. Logistic regression analysis and proportional hazards modeling were used to investigate whether sex or surgery type were associated with early mortality and late outcomes (mortality, major cardiac and cerebral event). RESULTS Female sex was associated with higher rates of early death (adjusted odds ratio, 4.726; p < 0.0001), and OPCAB benefited women disproportionately for early mortality. Odds ratio of death for women versus men was 4.726 (p < 0.0001) in the conventional CABG on cardiopulmonary bypass group; odds ratio of death for women versus men was 1.344 (p = 0.5617) in the OPCAB group. Analysis of late outcomes indicated that OPCAB and cardiopulmonary bypass resulted in similar survival, regardless of sex. The women versus men hazard ratio of late mortality after CABG on cardiopulmonary bypass and OPCAB for women was 0.851 (p = 0.4984) and 0.650 (p = 0.2005), respectively. Women treated with OPCAB were less likely to be free from major cardiac and cerebral events than men treated with OPCAB. The women versus men hazard ratio of major cardiac and cerebral events after CABG on cardiopulmonary bypass and OPCAB for women was 1.079 (p = 0.4992) and 1.299 (p = 0.0387), respectively. CONCLUSIONS Compared with men, women are a high-risk group and benefit from off-pump operation in terms of early mortality after CABG. Conversely, during follow-up, women have high adjusted risks of major cardiac and cerebral events after OPCAB.

Impact of Renal Dysfunction on Long-Term Survival After Isolated Coronary Artery Bypass Surgery

BACKGROUND Preoperative renal dysfunction has been an important predictor for adverse cardiovascular events after coronary artery bypass grafting (CABG). In the past, serum creatinine was widely used to assess renal function. Until recently, estimated glomerular filtration rate (eGFR) was recommended in evaluating renal function. The Cockcroft-Gault formula and the Modification of Diet in Renal Disease (MDRD) equation are two widely used formulas in clinical practice. Which method best predicts long-term outcome after CABG is still unknown. This study compared the predictive effectiveness of the Cockcroft-Gault formula, the MDRD equation, and serum creatinine level for in-hospital and long-term mortality. METHODS We retrospectively reviewed data collected from 5559 patients who underwent isolated CABG at Fuwai Hospital from January 1999 to December 2005. The main outcomes were in-hospital and long-term mortality. Receiver operating characteristic (ROC) curves and Cox analysis were used for the comparison. RESULTS Mean follow-up was 56.5 +/- 24.6 months. ROC curve analysis showed that the Cockcroft-Gault formula had the greatest accuracy for predicting in-hospital mortality (area under the curve, 0.755; p < 0.001). Multivariate analysis confirmed that the eGFR based on the Cockcroft-Gault formula was an independent predictor of in-hospital (odds ratio, 4.51, p < 0.001) and long-term (hazard ratio, 1.54; p = 0.003) mortality. Both formulas were better than the serum creatinine level. CONCLUSIONS Both formulas could provide a better measure of risk assessment than serum creatinine for in-hospital and long-term mortality. The Cockcroft-Gault formula was better than the MDRD equation for predicting in-hospital mortality.

A comparison before and after aprotinin was suspended in cardiac surgery: Different results in the real world from a single cardiac center in China

OBJECTIVE Use of aprotinin has been suspended in cardiac surgery since recent studies reported its risks associated with mortality and other adverse events. This study was to investigate the safety and efficacy of aprotinin through a comparison before and after aprotinin was suspended in cardiac surgery. METHODS We designed a case-control study in two groups of patients who underwent cardiac surgery just before and after aprotinin was suspended in China. The aprotinin group (n = 1699) was defined as operations performed from June 19, 2007, to December 18, 2007, when aprotinin was used in all the patients. The control group (n = 2225) was defined as operations performed from December 19, 2007, to June 18, 2008, when aprotinin was not used. We compared early postoperative outcomes between the two groups. RESULTS The aprotinin group had less postoperative blood loss, transfusion requirement, and reoperation for bleeding. Application of aprotinin did not increase the risk of in-hospital mortality (0.5% vs 1.0%; P = .08) and other major adverse outcome events, including renal, cardiac, neurologic, and pulmonary complications. The aprotinin group had a shorter mechanical ventilation time (P = .04), a lower rate of delayed mechanical ventilation time (P = .04), and a higher arterial oxygen tension/inspired oxygen fraction ratio in arterial blood gas analysis (P < .001). Multivariable logistic regression analysis confirmed findings from univariate analysis. After propensity adjustment for the baseline characteristics, we obtained similar results. CONCLUSIONS Use of aprotinin in cardiac surgery could reduce blood loss and transfusion requirement significantly and showed a protective effect on the lungs, but it did not increase the risk of mortality or major complications.

Effects of Aprotinin on Short-Term and Long-Term Outcomes After Coronary Artery Bypass Grafting Surgery

BACKGROUND Recent studies demonstrated that aprotinin use would increase the short-term and long-term mortality and complications after coronary artery bypass grafting (CABG). This study was to investigate effects of aprotinin during isolated primary CABG on short-term and long-term outcomes in Chinese patients. METHODS We studied 5,103 consecutive Chinese patients who underwent isolated primary CABG from 1999 to 2005. Of all the patients, 4,122 received aprotinin during operation (aprotinin group) and 981 received no aprotinin or other antifibrinolytic therapy (control group). Short-term and long-term mortality and major complications were analyzed with multivariate regression analysis. Propensity adjustment method was used to minimize the selection bias between the two groups, and propensity matching method was used to yield two well-matched groups for further comparison. RESULTS Blood loss after operation was significantly reduced in the aprotinin group compared with the control group (p < 0.001). Aprotinin use was neither associated with the perioperative mortality (p = 0.45, relative risk, 1.34) or major complications, nor was it associated with long-term mortality (p = 0.21, relative risk, 1.26) and major adverse cardiac and cerebrovascular events (p = 0.82, relative risk, 0.98). After propensity adjustment for the baseline characteristics, we obtained similar results. In addition, comparison between the two well-matched groups showed no significant difference either in baseline characteristics or in short-term and long-term outcomes. CONCLUSIONS Aprotinin use during isolated primary CABG reduced blood loss significantly, but was not associated with short-term or long-term mortality and complications. Aprotinin use in relatively low-risk CABG patients was effective and safe in a Chinese (Asian) population.

Impaired myocardium energetics associated with the risk for new-onset atrial fibrillation after isolated coronary artery bypass graft surgery.

BackgroundNew-onset postoperative atrial fibrillation (POAF) is one of the most common complications occurring in 10–40% of patients after coronary artery bypass graft (CABG) surgery. Recent studies suggest that dysmetabolism may contribute to the pathogenesis of atrial fibrillation; however, the putative mechanism in patients undergoing CABG surgery is unknown. Peroxisome proliferator-activated receptor &ggr; coactivator-1&agr; (PGC-1&agr;) has been demonstrated as a master regulator of myocardial energy metabolism, and glucose transporter 3 (GLUT3) has both a higher affinity for glucose and a much greater transport capacity compared with GLUT1, GLUT2, and GLUT4. We sought to evaluate the role of energy metabolism, especially the glucose metabolism, on patients after isolated CABG surgery. Methods and resultsRight atrial appendages were obtained from 79 patients who were in normal sinus rhythm and undergoing isolated CABG; those who exhibited new-onset POAF (n=22) or remained in sinus rhythm (n=57) were prospectively matched on the basis of preoperative, intraoperative, and postoperative characteristics. POAF was assessed by electrocardiogram and must have required the initiation of antiarrhythmic therapy or anticoagulation. Local PGC-1&agr; and GLUT3 concentrations were quantified by enzyme-linked immunosorbent assay in tissue homogenates. The comparison of mRNA expression was tested by quantitative real-time PCR. PGC-1&agr; and GLUT3 levels and the related protein mRNA expression were significantly reduced in POAF patients compared with controls (P<0.05). This selective reduction in PGC-1&agr; was associated with the presence of diabetes mellitus (P<0.05). ConclusionPatients who have low PGC-1&agr; and GLUT3 levels are at increased risk for new-onset POAF. The myofibrillar energetic impairment may be important in the pathogenesis of atrial fibrillation.

Surgery of left ventricular aneurysm: a propensity score-matched study of outcomes following different repair techniques☆

To evaluate early and late outcomes of modified left ventricular reconstruction (VR) and linear repair (LR) of post-infarct left ventricular aneurysm (LVA). A total of 514 patients were consecutively operated on for LVA with modified VR technique in 145 and LR in 352 patients. Using the propensity score-matching method, we selected 202 patients (101 LRs vs. 101 VRs) with similar pre- and intra-operative characteristics and compared their clinical outcomes. After matching, the two groups of patients were similar with regard to baseline data. The increment of left ventricular ejection fraction (LVEF) in VR group was more significant than that in LR group. Operative mortality was 2.0% (2.0% LRs vs. 2.0% VRs, P=NS). There was a statistically significant difference between LR and VR patients in MACCEs (29.7% LRs vs. 13.9% VRs, P<0.01) and hospital readmissions (51.5% LRs vs. 30.7% VRs, P<0.01). Overall long-term mortality and cardiac mortality were the same between the two groups (mortality: 11.9% LRs vs. 11.9% VRs, P=NS; cardiac mortality: 9.9% LRs vs. 7.9% VRs, P=NS). The technique of repairing LVA did not affect the early and later mortality.