Vincenzo De Amicis

Effect of rosuvastatin pretreatment on myocardial damage after coronary surgery: A randomized trial

OBJECTIVE Myocardial disease without evidence of myocardial infarction is a frequent complication after cardiac surgery during cardiopulmonary bypass. Statins might be protective, but their efficacy has not been established in randomized trials. METHODS Two hundred patients undergoing coronary surgery were enrolled. They were randomized to rosuvastatin (20 mg/d, n = 100) or placebo (n = 100) starting 1 week before the operation. Troponin I, myoglobin, creatine kinase-MB mass, and high-sensitivity C-reactive protein were used as markers of myocardial injury, and their values were determined at baseline and at regular intervals after the operation. Electrocardiography and echocardiography were performed before and after the operation. RESULTS Myocardial disease was diagnosed when troponin I, myoglobin, and creatine kinase-MB mass values were above the upper normal limit without evidence of electrocardiographic changes, echocardiographic changes, or both. The percentages of marker level increase indicative of myocardial disease were determined in the placebo versus statin groups and were as follows: troponin I, 35% versus 65% (P < .0001); myoglobin, 39% versus 72% (P < .0001); creatine kinase-MB mass, 22% versus 40% (P = .0002). Peak postoperative values of troponin I (0.16 +/- 0.15 vs 0.32 +/- 0.26 ng/mL, P = .0008), myoglobin (72.25 +/- 25 vs 98.31 +/- 31 ng/mL, P < .0001), and creatine kinase-MB mass (3.9 +/- 3.3 vs 9.3 +/- 8.1 ng/mL, P < .0001) were significantly higher in the placebo group. High-sensitivity C-reactive protein values were increased in 58% of pretreated versus 88% of the control patients (15.4 +/- 2.5 vs 17.2 +/- 3.4 mg/L, P < .0001). In high-risk patients myocardial disease was observed more frequently but significantly less in statin-pretreated patients. CONCLUSIONS Statin pretreatment reduces myocardial damage after coronary surgery and could improve both short- and long-term results.

Aspirin plus clopidogrel for optimal platelet inhibition following off-pump coronary artery bypass surgery: results from the CRYSSA (prevention of Coronary arteRY bypaSS occlusion After off-pump procedures) randomised study

Objective To determine the individual variability in the response to aspirin and/or clopidogrel and its impact on graft patency after off-pump coronary artery bypass grafting. Design A single-centre prospective randomised controlled study designed according to the Consolidated Standards of Reporting Trials statement. Randomisation was obtained by a computer-generated algorithm. Setting University medical school in Italy. Patients 300 patients who underwent off-pump coronary artery bypass grafting were randomised to receive aspirin (n=150) or aspirin plus clopidogrel (n=150). Intervention Aspirin 100 mg or aspirin 100 mg plus clopidogrel 75 mg daily was initiated when postoperative chest tube drainage was ≤50 ml/h for 2 h and patients were followed up for 12 months. Main outcome measures Qualitative and quantitative assessment of platelet function, angiographic evaluation of coronary revascularisation by 64-slice CT and clinical outcome. Results In the aspirin group, 49 patients (32.6%) were aspirin resistant and, in the aspirin-clopidogrel group, 19 patients (12.6%) were aspirin and clopidogrel resistant. The platelet response to aspirin was similar in all aspirin responders despite the study arm (Aspirin Reaction Units 313.2±44.8 vs 323.6±53.6; p=0.07). The platelet response to clopidogrel was enhanced by aspirin in patients responsive to both aspirin and clopidogrel (synergistic effect) compared with responders to clopidogrel only (P2Y12 Reaction Units 139.9±15.5 vs 179.4±18.5; p<0.001). Combined therapy was associated with a reduced vein graft occlusion rate (7.4% vs 13.1%; p=0.04). Antiplatelet resistance was a predictor of graft occlusion (RR 3.6, 95% CI 2.5 to 6.9; p<0.001). Synergistic aspirin and clopidogrel activity was a strong predictor of vein graft patency (RR 5.1, 95% CI 1.4 to 16.3; p<0.01). Conclusions Combined clopidogrel and aspirin overcome single drug resistances, are safe for bleeding and improve venous graft patency.

Influence of prosthesis–patient mismatch on exercise-induced arrhythmias: A further aspect after aortic valve replacement

OBJECTIVES The influence of prosthesis-patient mismatch on outcome after aortic valve replacement is controversial. This study analyzed the impact of prosthesis-patient mismatch on survival, the extent of left ventricular mass, and physical capacity after replacement with a small-size prosthesis. PATIENTS AND METHODS A total of 157 patients who underwent valve replacement for pure aortic stenosis were reviewed. Late mortality, morbidity, left ventricular mass regression, transprosthetic gradient at rest and after exercise, exercise capacity, and occurrence of arrhythmias were evaluated. RESULTS Prosthesis-patient mismatch, defined as an indexed effective orifice area of 0.75 cm(2)/m(2) or more, occurred in 96 (61.1%) patients and had no significant impact on early and late mortality. The only independent predictor of mortality was age greater than 65 years. At follow-up, multivariate analysis of prosthetic gradient at rest of 35 mm Hg end exercise capacity or more revealed that both these evidences were associated with high left ventricular mass (P < .001), female gender (P < .001), and follow-up time (P < .001). Arrhythmias occurred during exercise in 34.1% of patients (40/117). Multivariate analysis of occurrence of arrhythmias revealed that they were associated with high mean transprosthetic gradients: values of 50 mm Hg or more during exercise had 95% sensitivity and 72% specificity for predicting arrhythmias. CONCLUSION Prosthesis-patient mismatch failed to demonstrate any significant impact on early and late mortality and morbidity and in left ventricular mass regression. High transprosthetic gradients influence exercise capacity and occurrence of arrhythmias.

Previous Percutaneous Coronary Interventions Increase Mortality and Morbidity After Coronary Surgery

BACKGROUND This multicenter study investigated the impact of previous percutaneous coronary interventions (PCI) on postoperative outcome and 5-year survival of subsequent coronary artery bypass grafting. METHODS Among 7,855 patients who underwent isolated first-time coronary artery bypass grafting between January 2000 and December 2005, 6,834 (87%) had no previous PCI and 1,021 (13%) had previous PCI with stenting. Logistic multiple regression and propensity score analyses were used to assess the risk-adjusted impact of prior PCI on in-hospital mortality and major adverse cardiac events. The Cox regression model was used to assess the effect of prior PCI on 3-year and 5-year survival. RESULTS After risk-adjusted multivariate analysis, age over 70 years, female sex, 3-vessel or 2-vessel plus left main coronary disease, multivessel PCI, ejection fraction 0.40 or less, diabetes mellitus, previous myocardial infarction, and chronic obstructive pulmonary disease were identified as independent predictors of both hospital mortality and major adverse cardiac events. After propensity score matching, conditional logistic regression analysis identified history of previous PCI as significantly associated with an increased risk for hospital mortality (odds ratio, 2.8; 95% confidence interval 1.4 to 4.8; p=0.003) and major adverse cardiac events (odds ratio 2.1; 95% confidence interval 1.2 to 3.6; p<0.001). Survival at 3 and 5 years was lower in patients with previous PCI compared with the no-PCI patients (97.4%±0.01% vs 96.5%±0.02% and 94.2%±0.03% vs 92.1%±0.05%; log-rank test: p=0.03). CONCLUSIONS Our results provided further evidence that history of PCI before coronary artery bypass grafting increases risk of both operative death and perioperative complications, and decreases survival at 5 years follow-up.

Intermittent Warm Blood Cardioplegia Preserves Myocardial β-Adrenergic Receptor Function

BACKGROUND Left ventricular dysfunction is frequently observed in patients after hypothermic cardioplegic arrest, and often inotropic intervention is necessary for patients to be successfully weaned from cardiopulmonary bypass (CPB). A myocardial beta-adrenergic receptor (beta AR) desensitization has been noted to occur after hypothermic CPB in patients undergoing coronary artery bypass grafting. This randomized study was undertaken to determine the effect of cardioplegic solution temperature on cardiac beta ARs. METHODS Two groups of patients (20 patients in each) scheduled for elective coronary artery bypass grafting underwent CPB with either intermittent warm or cold blood cardioplegia. The density of the beta ARs, the proportion of beta 1- to beta 2-adrenergic receptors, and the beta AR coupling capacity to adenylate cyclase were determined in specimens of the right atrial tissue at baseline, during CPB, and after discontinuation of CPB. Plasma concentrations of catecholamines were also measured in both arterial and coronary sinus samples. RESULTS In both cardioplegia groups, no significant modification in either the beta AR density or the proportion of beta 1- to beta 2-adrenergic receptors was detected. However, a significant decrease in adenylate cyclase activity after stimulation with isoproterenol was observed in the cold blood cardioplegia group during CPB (p < 0.01) and 30 minutes after its discontinuation (p < 0.05). Moreover, a significant decrease in adenylate cyclase activity during CPB was detected in this group after stimulation with sodium fluoride (p < 0.05), but this pattern was found to be completely reversed by 30 minutes after discontinuation of CPB. No modification in the basal or stimulated adenylate cyclase activity was observed in the warm blood cardioplegia group during or after CPB. CONCLUSIONS Our results confirm the finding from previous studies of a cardiac beta AR desensitization after hypothermic cardioplegic arrest, and provide evidence of the advantages of intermittent warm blood cardioplegia in preserving the autonomic sympathetic function of the heart.

Randomized flow capacity comparison of skeletonized and pedicled left internal mammary artery.

BACKGROUND The preferential harvesting technique of the internal mammary artery has been periodically debated. This randomized study evaluated the flow outcome of the skeletonized versus pedicled left internal mammary artery. METHODS Two hundred patients undergoing surgery for left anterior descending coronary artery revascularization were enrolled and randomized to pedicled (n=100) or skeletonized (n=100) harvesting. Intraoperative baseline flow and post adenosine infusion into the left ventricle, hospital outcome, echocardiographic results, and troponin I leakage were analyzed. Noninvasive periodic evaluation of flow was carried out at rest and during intravenous adenosine infusion by transthoracic Doppler ultrasound, and was stratified according to the harvesting technique. Final angiographic evaluation was performed by 64-slice multidetector computed tomography. RESULTS Skeletonized left internal mammary arteries demonstrated better flow capacity at rest and during adenosine recruitment perioperatively and at all time points of follow-up. Troponin I leakage was significantly higher in the pedicled group (59 vs 42, p=0.02). Pedicled harvesting (hazard ratio [HR] 3.6, 95% confidence interval [CI] 2.5 to 6.9, p<0.001); indexed left ventricular mass greater than 150 g/m2 (HR 4.6, 95% CI 3.1 to 7.5, p<0.001); and baseline corrected thrombolysis in myocardial infarction frame count greater than 30 (HR 4.4, 95% CI, 3.8 to 7.2, p<0.001) were the most powerful multivariable predictors of graft flow reserve less than 2.0. Postoperative echocardiographic results and clinical and angiographic outcomes were comparable between the two groups. CONCLUSIONS Skeletonization of the left internal mammary artery, beyond traditional proven advantages, provided significantly higher flow capacity and better graft flow reserve.

Changes in skeletal muscle histology and metabolism in patients undergoing exercise deconditioning: Effect of propionyl‐L‐carnitine

To define the skeletal muscle abnormalities in patients undergoing exercise deconditioning and evaluate the metabolic effect of propionyl‐L‐carnitine (PLC), muscle biopsies were obtained from 28 patients with effort angina and 31 control subjects. Coronary artery disease patients received either placebo (n = 12), PLC (1.5 g IV followed by infusion of 1 mg/kg/min for 30 min, n = 10), or L‐carnitine (1 g IV followed by infusion of 0.65 mg/kg/min for 30 min, n = 6) for 2 days. Exercise deconditioned patients treated with placebo showed normal muscle content of total carnitine and glycogen, and decrease in percentage of type 1 fibers (P < 0.01) and in the activity of citrate synthase (P < 0.05), succinate dehydrogenase (P < 0.05), and cytochrome oxidase (P < 0.05), as compared to controls. Both PLC and L‐carnitine did not modify muscle fiber composition or enzyme activities, but significantly increased muscle levels of total carnitine by 42% and 31%, respectively (P < 0.05). Moreover, PLC significantly increased glycogen muscle content (P < 0.01), while the equimolar dose of L‐carnitine did not. This effect, probably due to the anaplerotic activity of the propionic group of PLC, suggests that this drug may be effective in improving energy metabolism of muscles with impaired oxidative capacity.

Preoperative Intraaortic Balloon Pump for Off-Pump Coronary Arterial Revascularization

BACKGROUND Prophylactic intraaortic balloon pump (IABP) support showed better outcomes in critical patients undergoing coronary revascularization compared with intraoperative or postoperative insertion. We conducted a prospective, randomized study to determine the optimal timing for preoperative IABP insertion in high-risk patients undergoing off-pump coronary artery revascularization. METHODS The study enrolled 230 consecutive high-risk patients (having a logistic European System for Cardiac Operative Risk Evaluation score of ≥10) undergoing off-pump coronary artery revascularization. They were randomized for preoperative IABP starting at 2 hours (2T, n=115) or 12 hours (12T, n=115). Clinical, biochemical, and hemodynamic results, and the need for inotropic drug support, were markers of outcome and compared between groups. RESULTS Hospital mortality in group 12T was reduced by 60%, but the difference between groups was not statistically significant (hazard ratio, 0.4; 95% confidence interval, 0.1 to 1.5; p=0.1). Twelve hours of preoperative IABP therapy reduced postoperative low output syndrome (hazard ratio, 0.4; 95% confidence interval, 0.1 to 0.9; p=0.03) and biomarker leakage upper normal limit (hazard ratio, 0.3; 95% confidence interval, 0.1 to 0.7; p=0.001). Postoperative left ventricular function was similar between the groups. Group 2T patients required higher inotropic support for a longer average duration and prolonged postoperative intensive care unit and hospital length of stay. CONCLUSIONS Twelve hours preoperative IABP therapy improved treatment efficacy. Postoperative morbidity was reduced, but hospital mortality rate was not affected. The IABP-related complication rate was low and not related to the length of treatment.

Serial Evaluation of Flow in Single or Arterial Y-Grafts to the Left Coronary Artery

BACKGROUND It is unclear whether composite Y-grafts can withstand the flow demand of the coronary system at rest and under stress. This study compared the graft flow and flow reserve of the left internal mammary artery (LIMA) intraoperatively and over a 2-year follow-up in single or composite Y-graft configurations using the radial artery (RA). METHODS One hundred patients who underwent off-pump myocardial revascularization with a composite Y-graft (group 2) were compared with a homogeneous group of 100 patients treated with a single independent LIMA graft on the left anterior descending artery (LAD) (group 1). Intraoperative baseline flow and flow after adenosine infusion into the left ventricle were analyzed. Over a 2-year follow-up, noninvasive longitudinal evaluation of flow was carried out at rest and during maximal hyperemic response by transthoracic Doppler ultrasonography. Final functional evaluation was obtained through a 2-day stress/rest 99mTc-sestamibi myocardial perfusion single-photon emission computed tomographic scan. RESULTS The proximal LIMA in a Y-graft configuration showed adaptability to flow dynamics. It had a greater average peak velocity (p = 0.02), flow volume (p < 0.01), and diameter (p < 0.01) than independent single LIMA grafts. Distal flow at rest and during adenosine recruitment was similar between groups both intraoperatively and at all time points of the follow-up. No steal phenomenon occurred at rest, nor was it induced by adenosine in the Y-graft group. Exercise nuclear scintigraphy showed satisfactory exercise tolerance and no inducible significant perfusion defects in both groups. CONCLUSIONS Left internal mammary artery Y-grafting with the RA is adequate for flow requirements of distal branches at rest and during maximal hyperemia and is able to adapt its dimension to flow demand. Optimal results for RA anastomoses are possible only in arteries with critical stenosis and of good size and quality.

Endothelial Nitric Oxide Synthase Expression in Postmenopausal Women: A Sex-Specific Risk Factor in Coronary Surgery

BACKGROUND After coronary artery bypass graft surgery, older women have less favorable clinical outcome and lower conduit patency compared with men. This less favorable outcome can be in part ascribed to impaired endothelium-derived nitric oxide (eNOS) production. This study evaluated endothelial nitric oxide synthase expression in internal mammary artery from postmenopausal women undergoing coronary artery bypass graft surgery. METHODS Internal mammary artery segments were obtained from 20 postmenopausal woman and 20 matched male patients. Twenty more segments from younger patients were used as controls. Expression of eNOS messenger RNA in internal mammary artery endothelial cells were evaluated by polymerase chain reaction and real-time quantitative reverse transcription polymerase chain reaction. The eNOS protein level was assayed by Western blot. Vascular dynamics of specimens were evaluated by organ chamber methodology. RESULTS In postmenopausal women, the band of messenger RNA for eNOS was reduced by 37.4% and by 25.2%, respectively, compared with matched men and the control group (62.6%±4.8% versus 74.8%±5.3%, p<0.001). In comparison with the control group lane, the eNOS protein immunoreactive band was 44.2% decreased in postmenopausal women and 34.5% decreased in matched men, and was significantly decreased in postmenopausal women as compared with matched men (55.8%±4.6% versus 65.5%±5.2%, p<0.001). Nitric oxide-mediated vasomotor dynamics were consistent with reduced eNOS production. CONCLUSIONS Internal mammary artery endothelial cells from women after menopause undergoing coronary surgery have impaired expression of messenger RNA for eNOS and reduced eNOS levels. Reduced bioactivity of nitric oxide translates into impaired endothelial metabolism that could contribute to worse surgical outcome.