Ram Sharony

Off-Pump Coronary Artery Bypass Grafting Reduces Mortality and Stroke in Patients With Atheromatous Aortas: A Case Control Study

Background—Patients with severe atheromatous aortic disease (AAD) who undergo coronary artery bypass (CABG) have an increased risk of death and stroke. We hypothesized that in these high risk patients, off-pump coronary artery bypass (OPCAB) technique is associated with lower morbidity and mortality. Methods and Results—Between June 1993 and January 2002, 5737 patients undergoing CABG had routine intra-operative TEE with 913 (15.9%) found to have severe AAD in the aortic arch or ascending aorta. Of these, 211 patients who underwent OPCAB were matched with 211 on-pump CABG patients by age, ejection fraction, history of stroke, cerebrovascular disease, diabetes, renal disease, nonelective operation, and previous cardiac surgery. Hospital mortality was 11.4% (24/211) for on-pump CABG and 3.8% (8/211) for OPCAB (P =0.003). Multivariate analysis revealed that increased mortality was associated with on-pump CABG (P =0.001), acute MI (P =0.03), number of grafts (P =0.01), age (P =0.01), history of stroke or cerebrovascular disease (P =0.04), CHF (P =0.02), and peripheral vascular disease (P =0.03). Multivariate analysis showed that OPCAB technique was associated with decreased stroke (P =0.05). Freedom from any complication was 78.7% for on-pump CABG and 91.9% for OPCAB (P <0.001). At 36 month follow-up multivariate analysis revealed that increased mortality was associated with age (P =0.001), previous MI (P =0.03), and renal disease (P =0.04), whereas increased survival was associated with increased number of grafts (P =0.001) and OPCAB (P =0.01). Conclusions—OPCAB surgery in patients with severe AAD is associated with lower risk of death, stroke and complications and improved mid-term survival. Routine intra-operative TEE allows identification of these patients and directs choice of appropriate surgical technique.

Aortic valve replacement in patients with impaired ventricular function

BACKGROUNDnPatients with reduced ventricular function undergoing aortic valve replacement have increased operative risks, but the impact of valvular pathophysiology and other risk factors has not been clearly defined.nnnMETHODSnFrom June 1992 through June 2002, 1,402 consecutive patients underwent isolated aortic valve surgery with or without coronary artery bypass grafting; of these patients, 416 had an ejection fraction less than 40% and are the subject of this report. These patients (mean age, 68.6) had severe stenosis (62.5%), severe regurgitation (30.3%), or mixed disease (7.2%). Aortic valve replacement plus coronary artery bypass grafting was performed in 48.4% of patients, and 27% had previous cardiac surgery. Follow-up included echocardiography and survival analysis.nnnRESULTSnHospital mortality was 10.1% (42 of 416), with no difference between aortic stenosis (9.6%) and regurgitation (11.1%). Multivariate analysis revealed that age (p = 0.002) and renal disease (odds ratio = 4.2; 95% confidence interval, 1.9 to 9.3; p = 0.001) were independently associated predictors of mortality. Valvular pathophysiology had no impact on mortality. Peripheral vascular disease, multivessel coronary disease, and renal disease were associated risks for any postoperative complication. Peripheral vascular disease (odds ratio = 12.3, p = 0.02), history of cerebrovascular disease (odds ratio = 4.8, p = 0.038), and diabetes (odds ratio = 2.7, p = 0.04) were associated risks for stroke. The ejection fraction was more than 40% in 52% of the patients who had postoperative echocardiography (mean follow-up, 6 months). Actuarial survival revealed no difference between pathophysiologic groups.nnnCONCLUSIONSnAortic valve surgery in patients with impaired ventricular function carries an acceptable operative risk that can be stratified by age and comorbidities. The type of valvular pathophysiology does not significantly affect mortality.

Minimally Invasive Reoperative Isolated Valve Surgery: Early and Mid-Term Results

Abstractu2002 Objective: Minimally invasive, nonsternotomy approaches for valve procedures may reduce the risks associated with cardiac surgery after prior sternotomy and may improve outcomes. We analyzed our institutional experience to test this hypothesis. Methods: Between 1995 and 2002, 498 patients with previous cardiac operations via sternotomy underwent isolated valve surgery: 337 via median sternotomy (aortic = 160; mitral = 177) and 161 via mini‐thoracotomy (aortic = 61; mitral = 100). Data were collected prospectively using the New York State Cardiac Surgery Report Form. Results: Preoperative incidences of congestive heart failure, renal disease, and nonelective procedures were higher in the sternotomy group. Hospital mortality was significantly lower with the minimally invasive approach, 5.6% (9/161) versus 11.3% (38/337) (univariate, p = 0.04). However, multivariate analysis (odds ratio: 95% confidence intervals, p value) revealed that chronic obstructive pulmonary disease (6.6: 1.4 to 3.1, p = 0.001), renal disease (4.1: 1.52 to 11.2, p = 0.01), cerebrovascular disease (2.2: 1.03 to 4.78, p = 0.04), and ejection faction <30% (1.5: 0.96 to 5.5, p = 0.06) were associated with increased mortality. While mean bypass time, cross‐clamp times, and stroke rates were comparable between groups, patients undergoing minimally invasive valve surgery had no deep wound infections (0% vs 2.4%, p = 0.05), less need for blood products (p = 0.02), and shorter hospital stays (p = 0.009). Five‐year survival was higher with minimally invasive techniques as compared to a sternotomy approach (92.4 ± 2% and 86.0 ± 2%, respectively, p = 0.08). Conclusions: Reoperative valve surgery can be safely performed using a nonsternotomy, minimally invasive approach, with at least equal mortality, less hospital morbidity, decreased hospital length of stay, and slightly favorable mid‐term survival as compared to sternotomy.

Minimally Invasive Aortic Valve Surgery in the Elderly: A Case-Control Study

Introduction—Although minimally invasive aortic valve surgery (MIAVR) is performed in many centers, few studies have compared its results to a standard sternotomy (SS) approach. We assessed the hypothesis that, when compared with SS in the elderly population, MIAVR has similar morbidity and mortality and allows faster hospital recovery. Methods and Results—From January 1995 through February 2002, 515 patients over age 65 underwent isolated aortic valve replacement. Using data gathered prospectively, 189 MIAVR patients were matched with 189 SS patients by age, ventricular function, valvular pathology, urgency of operation, diabetes, previous cardiac surgery, renal disease, and history of stroke. In each group, 56.1% of patients underwent non-elective procedures, and 28% were ≥80 years old. Hospital mortality (6.9%) and freedom from postoperative morbidity (82.5% versus 81.5%, P =0.79) were similar. Multivariate analysis revealed that urgent procedures [Odds Ratio (OR)=3.97; P =0.03], congestive heart failure (OR=3.94; P =0.03), and ejection fraction <30% (OR=4.16; P =0.03) were significant predictors of hospital mortality. Prolonged length of stay was associated with age (P =0.05), preoperative stroke (OR=3.5, P =0.001), CHF (OR=2.2, P =0.004), and sternotomy approach (OR=2.3, P =0.002) by multivariate analysis. More MIAVR patients were discharged home (52.6% versus 38.6%, P =0.03) rather than to rehabilitation facilities. Three year actuarial survival revealed no difference between groups. Conclusions—Minimally invasive aortic valve surgery is safe in elderly patients, with morbidity and mortality comparable to sternotomy approach. The shorter hospital stay and greater percentage of patients discharged home after MIAVR reflect enhanced recovery with this technique.

Strict Thermoregulation Attenuates Myocardial Injury During Coronary Artery Bypass Graft Surgery as Reflected by Reduced Levels of Cardiac-Specific Troponin I

We assessed the cardioprotective effects of perioperative maintenance of normothermia by determining the perioperative profile of troponin I, a highly cardiac-specific protein important in risk stratification of patients with acute ischemic events. Candidates for their primary coronary artery bypass grafting (CABG) were randomized into a new thermoregulation system group, Allon( thermoregulation (AT; n = 30), and a routine thermal care (RTC; n = 30) group. Anesthetic and operative techniques were similar in both groups. Intraoperative warming was applied before and after cardiopulmonary bypass (CPB) and up to 4 h after surgery. Perioperative temperature and hemodynamic data were recorded. Blood samples for creatine kinase (CK) and its isoform, MB (CK-MB), and for cardiac-specific troponin I (cTnI) were obtained at predetermined intervals throughout the entire operation. Core and skin temperatures were higher in the AT group at all time points. The systemic vascular resistance was lower and the cardiac index higher in the AT group at all intra- and postoperative time points. Increases in CK, CK-MB, and cTnI levels indicated intraoperative ischemic insult in all patients. The respective CK levels for the AT and RTC groups were 53.3 +/- 22.7 IU/L and 47.9 +/- 17.86 IU/L at the time of anesthesia and 64.7 +/- 45.6 IU/L and 47.8 +/- 19.4 IU/L 30 min after the onset of surgery, demonstrating thereafter a steep increase before the discontinuation of CPB. CK-MB mass concentrations in both groups behaved almost identically. Pre-CPB cTnI levels at anesthesia induction were 0.3 +/- 0 ng/mL in both groups, followed by a distinctive profile observed after separation from CPB: 28.1 +/- 11.4 ng/mL, 26.05 +/- 9.20 ng/mL, and 22.3 +/- 8.9 ng/mL at discontinuation from CPB, chest closure, and 2 h after surgery, respectively, in the RTC group, versus 0.6 +/- 4.6 ng/mL, 6.6 +/- 5.5 ng/mL, and 7.9 +/- 4.76 ng/mL at these three time points, respectively, in the AT group (P < 0.01 between groups at the specified time points). Contrary to conventional thinking about the benefits of hypothermia, maintenance of normothermia throughout the non-CPB phases during CABG was demonstrated to be important in attenuating myocardial ischemic injury. Insofar as troponin I was more sensitive than other tested markers, it may provide important data on possible protection from myocardial insult and on other cardioprotective measures.

Pharmacokinetics of vancomycin administered as prophylaxis before cardiac surgery.

Vancomycin concentrations in serum, tissues, and sternum, administered as prophylaxis to patients during coronary artery bypass surgery, were measured. Vancomycin (15 mg/kg) was administered to 15 patients 1 hour before skin incision. Blood, tissue, and sternum samples were collected before, during, and after bypass. The concentration in serum at the end of infusion was 55.1 ± 22.8 &mgr;g/mL, the mean elimination half-life was 9 ± 4 hours, the areas under the concentration–time curve (AUC) from 0 to 12 hours and from 0 to infinity were 90.6 ± 25.1 and 289.7 ± 86.5 &mgr;g/h per mL, respectively, the mean residence time (MRT) was 11.9 ± 5.0 hours, the mean volume of distribution was 51.1 ± 12.2 L, and the total clearance was 78.3 ± 32.6 mL/min. Vancomycin concentrations in serum, tissues, and sternum during the operation were greater than the MIC90 for most staphylococci and ranged from 16 to 55 &mgr;g/mL in serum and from 4 to 39 &mgr;g/g in sternum and tissues.

Induction of stromelysin‐1 (MMP‐3) by fibroblast growth factor‐2 (FGF‐2) in FGF‐2−/− microvascular endothelial cells requires prolonged activation of extracellular signal‐regulated kinases‐1 and ‐2 (ERK‐1/2)

Basic fibroblast growth factor (FGF‐2) and matrix metalloproteinases (MMPs) play key roles in vascular remodeling. Because FGF‐2 controls a number of proteolytic activities in various cell types, we tested its effect on vascular endothelial cell expression of MMP‐3 (stromelysin‐1), a broad‐spectrum proteinase implicated in coronary atherosclerosis. Endothelial cells (EC) from FGF‐2−/− mice are highly responsive to exogenous FGF‐2 and were therefore used for this study. The results showed that treatment of microvascular EC with human recombinant FGF‐2 results in strong induction of MMP‐3 mRNA and protein expression. Upregulation of MMP‐3 mRNA by FGF‐2 requires de novo protein synthesis and activation of the ERK‐1/2 pathway. FGF‐2 concentrations (5–10 ng/ml) that induce rapid and prolonged (24 h) activation of ERK‐1/2 upregulate MMP‐3 expression. In contrast, lower concentrations (1–2 ng/ml) that induce robust but transient (<8 h) ERK‐1/2 activation are ineffective. Inhibition of ERK‐1/2 activation at different times (−0.5 h to +8 h) of EC treatment with effective FGF‐2 concentrations blocks MMP‐3 upregulation. Thus, FGF‐2 induces EC expression of MMP‐3 with a threshold dose effect that requires sustained activation of the ERK‐1/2 pathway. Because FGF‐2 controls other EC functions with a linear dose effect, these features indicate a unique role of MMP‐3 in vascular remodeling.

Anti-proliferative and anti-inflammatory effects of topical MAPK inhibition in arterialized vein grafts

Vein graft failure following bypass surgery is a frequent and important clinical problem. The vascular injury caused by arterialization is responsible for vein graft intimal hyperplasia, a lesion generated by medial smooth muscle cell proliferation and migration into the intima, increased extracellular matrix deposition, and formation of a thick neointima. Development of the neointima into a typical atherosclerotic lesion and consequent stenosis ultimately result in vein graft failure. Endothelial damage, inflammation, and intracellular signaling through mitogenactivated protein kinases (MAPKs) have been implicated in the early stages of this process. We therefore investigated the effects of topical inhibition of ERK‐1/2 MAPK activation on vascular cell proliferation and apoptosis, and on the inflammatory response in a canine model of vein graft arterialization. For this purpose, vein grafts were incubated with the MEK‐1/2 inhibitor, UO126, ex vivo for 30 min before grafting. This treatment effectively abolished arterializationinduced ERK‐1/2 activation, decreased medial cell proliferation, and increased apoptosis. UO126 treatment also inhibited the vein graft infiltration by myeloperoxidase‐positive inflammatory cells that follows vein graft arterialization. Thus, topical ex vivo administration of MAPK inhibitors can provide a pharmacological tool to prevent or reduce the vascular cell responses that lead to vein graft intimal hyperplasia and graft failure.

Routine intraoperative transesophageal echocardiography identifies patients with atheromatous aortas: impact on “off-pump” coronary artery bypass and perioperative stroke

BACKGROUNDnPatients with severe atheromatous aortic disease (AAD) undergoing coronary artery bypass grafting (CABG) have increased operative risks. The off-pump CABG (OPCAB) technique was evaluated in patients given the diagnosis of severe AAD by routine transesophageal echocardiography.nnnMETHODSnA total of 5737 patients underwent CABG, with 913 having transesophageal echocardiography findings of severe AAD. Of the patients with severe AAD, 678 (74.3%) had conventional CABG and 235 (25.7%) had OPCAB.nnnRESULTSnHospital mortality was 8.7% for conventional CABG and 5.1% for OPCAB (P =.08). Multivariate analysis revealed that increased mortality was significantly associated with acute myocardial infarction, conventional CABG, age, renal disease, history of stroke, and ejection fraction < 30%. Neurologic complications occurred in 6.3% of patients undergoing CABG and in 2.1% undergoing OPCAB (P =.01). Freedom from any complication was significantly greater with OPCAB.nnnCONCLUSIONnRoutine intraoperative transesophageal echocardiography identifies patients with severe AAD. In these patients, OPCAB technique is associated with a lower risk of death, stroke, and all complications.

Computer-generated three-dimensional animation of the mitral valve

OBJECTIVEnThree-dimensional motion-capture data offer insight into the mechanical differences of mitral valve function in pathologic states. Although this technique is precise, the resulting time-varying data sets can be both difficult to interpret and visualize. We used a new technique to transform these 3-dimensional ovine numeric analyses into an animated human model of the mitral apparatus that can be deformed into various pathologic states.nnnMETHODSnIn vivo, high-speed, biplane cinefluoroscopic images of tagged ovine mitral apparatus were previously analyzed under normal and pathologic conditions. These studies produced serial 3-dimensional coordinates. By using commercial animation and custom software, animated 3-dimensional models were constructed of the mitral annulus, leaflets, and subvalvular apparatus. The motion data were overlaid onto a detailed model of the human heart, resulting in a dynamic reconstruction.nnnRESULTSnNumeric motion-capture data were successfully converted into animated 3-dimensional models of the mitral valve. Structures of interest can be isolated by eliminating adjacent anatomy. The normal and pathophysiologic dynamics of the mitral valve complex can be viewed from any perspective.nnnCONCLUSIONnThis technique provides easy and understandable visualization of the complex and time-varying motion of the mitral apparatus. This technology creates a valuable research and teaching tool for the conceptualization of mitral valve dysfunction and the principles of repair.