Approximately 350,000 patients undergo coronary artery bypass (CABG) surgery annually in the United States Saphenous vein grafts account for 70% of all grafts placed during CABG. Long-term studies have observed an incidence of vein graft occlusion at 19% at 1 year, 25% at 5 years, and 50% by, or at 15 years. Neointimal hyperplasia, which is the accumulation of smooth muscle cells and extracellular matrix in the intimal compartment of vein grafts, is the pathological process that underlies graft atherosclerosis and subsequent graft degeneration. Nearly all veins implanted in the arterial circulation develop intimal thickening within 4 to 6 weeks leading to the major disease process, which occurs, between one month and one year after implantation. Stimulation of smooth muscle cells is a key initiating process to neointimal hyperplasia and is activated by a family of transcription factors E2F.

A novel therapy has been developed by which this transcription factor activity can block by treatment of the cells with double-stranded oligonucleotides (ODN). These ODN act as "decoys" for the transcription factors (E2F decoy) and by binding to the factor, prevent its interaction with chromosomal DNA and subsequent gene activation. This unique therapy of treating saphenous vein grafts ex-vivo at the time of harvest has been shown in early trials (Prevent I and Prevent II) to improve saphenous vein graft patency.

Based upon this promising data, a multi-center national randomized trial will be conducted. The saphenous vein grafts will be treated for 10 minutes in a pressurized chamber at the time of harvest with either the E2F decoy (CGT003) or a placebo. Three thousand patients will be randomized at the initial hospital procedure and the first 2,400 of these will undergo angiographic follow-up at 12 months and will be included in the long-term follow-up for Major Adverse Cardiac Events (MACE). Patients eligible for entry into the trial include those who are undergoing isolated coronary artery bypass grafting and have at least two grafts being performed with saphenous
vein grafts. One hundred investigational sites will participate in
the study including the three CRSTI sites. The trial, Prevent IV, is expected to begin enrolling patients June 30, 2002 and will take 9 months to complete enrollment. Members of the CRSTI research team are participating in the steering committee for the trial, in which the Duke Clinical Research Institute (DCRI) will administer the study in conjunction with the Society of Thoracic Surgeons Database Committee.

Based upon early studies with treatment of saphenous vein grafts with E2F decoy in both peripheral vascular and coronary bypass surgery, hopes are that the results of this trial will demonstrate a prolongation of graft survival and long-term patency in coronary artery bypass surgery.

Dr. Michael Mack is a practicing
cardiothoracic surgeon with COR
Specialty Associates of North Texas, PA (CSANT) and President/Chairman of CRSTI.

Cayla graduated from Mesquite High School in Mesquite, Texas. She is currently enrolled at Eastfield College, pursuing her Bachelor of Science degree.

Prior to joining CRSTI, Cayla worked for Tutor Time as a teacher for children ages 3 and 5. Cayla is married with one son, Austin. She and her family reside in Mesquite.

CRSTI researchers recently led and completed a multi-center study, Comparison of Coronary Artery Bypass Surgery (CABG) with and without Cardiopulmonary Bypass in Patients with Multivessel Disease, with nationally recognized research centers Lenox Hill Hospital in New York, NY; Cardiac Surgical Associates, P.A., in Minneapolis, MN and Washington Hospital Center in Washington, D.C.

The objective of the study was to determine whether off pump CABG
(OPCAB) is associated with better early outcomes compared with conventional CABG. The study utilized data from four centers with significant off-pump surgery experience.

Researchers Michael J. Mack, M.D., Albert Pfister, M.D., Donna Bachand, R.N., PhD, Robert Emery, M.D., Mitchell J. Magee, M.D., Mark Connolly, M.D., and Valavanur Subramanian, M.D. performed a retrospective analysis of all CABG patients in a two year period.

Groups were compared to determine selection criteria, mortality and morbidity; then propensity score computer matched to control for selection bias. Multivariate logistic regression (MLR) identified risk factors predictive of mortality. Specific subgroups most likely to benefit were identified.

12,566 isolated CABG were performed, 6,576 (52.3%) OPCAB and 5,990
(47.7%) CABG-CPB. Patients more often selected for OPCAB included female gender (55.5% vs. 44.5%), pre-existing renal failure (57.0% vs. 43.0%), and reoperations (52.6% vs. 47.4%). Operative mortality was 2.9%; OPCAB vs. CABG-CPB (1.9% vs. 3.8%, p<.001) with the same predicted risk.

7,396 multi-vessel diseased patients were propensity score computer matched to coventional CABG patients To minimize selection bias, 7,396 multi-vessel. Off pump CABG was associated with significantly less mortality (2.0% vs. 3.6%, p < .001) and morbidity including transfusion need, stroke, pulmonary complications, renal failure, reoperation for bleeding, and atrial fibrillation. High risk patients including females, reoperations, and pre-existing renal failure or stroke had the greatest benefit.

Concludsion: In centers with significant OPCAB experience, there is an overall early benefit in off-pump surgery - especially in patients traditionally considered high-risk for CABG.

CRSTI researchers Jeffrey L. Horswell MD, Michael J. Mack MD, Donna A Bachand RN PhD, Luis Michelsen MD, and Tina Worley RN BSN CCRC, recently completed a randomized, double-blind study on the use of Dexmedetomidine as an adjunct to pain control following OPCAB.

The purpose of this study was to determine whether use of dexmedetomidine (PrecedexTM) leads to improved clinical outcomes in immediately extubated, post-operative off-pump coronary artery bypass
(OPCAB) patients.

Twenty-four patients scheduled for elective OPCAB consented to participate in the study. Patients who were previously selected for epidural analgesia or who had elevated serum creatinine levels were excluded. Fifteen minutes prior to extubation, patients were prospectively randomized in a double-blind fashion into one of two
groups: Group 1 (n=12) received an 18 hour infusion of dexmedetomidine 0.2 to 0.7 ug/kg/hr. Group 2 (n=12) received an 18 hour infusion of normal saline. All patients received a standard anesthetic consisting of propofol, sufentanil, vecuronim, and desflurane.

Post-operative pain was managed with ketorolac and morphine. Total morphine use was recorded. Hemodynamic monitoring, incentive spirometry volumes, visual analog scale pain ratings, activity, and anxiety levels were recorded every 2 hours for 18 hours post-operatively.

The results were encouraging. The average narcotic use was 2.1 times greater in the placebo group compared to the treatment group . Adequate pain control was achieved with the patients in the treatment group more rapidly than the placebo group - 6 hours compared to the placebo group
at 8 hours. Although morphine doses were available on demand to all
patients, those in the treatment group reported less pain at all time
points and these patients were out of bed earlier There were no
significant changes in heart rate, blood pressure, pulmonary artery pressure, central venous pressure, cardiac output, or systemic oxygen saturation in either group. When hemodynamic data were analyzed by subject, no significant changes could be detected.

Researchers conclude Dexmedetomidine provides effective post-operative pain control without untoward hemodynamic changes in immediately extubated OPCAB patients. Superior pain control can be achieved with minimal doses of narcotics.

CRSTI participating physicians understand the importance of furthering research through education. That is why so many take an active role in presenting the latest research findings; surgical techniques and therapies to the medical and general communities.

Upcoming Educational Seminars

May 21 - Paris, France
“What will be the surgeon's response to this new challenge coming from the the interventional cardiologists?” Michael Mack, M.D., Cardiothoracic Surgeon

June 6 - Asheville, NC
“PRO: is there adequate coronary artery revascuarlization without the use of CPB?” Michael Mack, M.D., Cardiothoracic Surgeon

July 9 - Dallas, TX
“New advancements in the treatment of atrial fibrillation" The Mended Hearts, Inc. James Edgerton, M.D., Cardiothoracic Surgeon

Publications in Press

Mack MJ, Dewey TM, Magee MJ.
Facilitated anastomosis for reoperative beating heart circumflex coronary revascularization. J Thorac and Cardiovasc Surg 2002;123(4):816-817

Magee MJ, Jablonski KA, Stamou SC, Pfister AJ, Dewey TM, Dullum MKC, Edgerton JR, Prince SL, Acuff TE, Corso PJ, Mack MJ. Elimination of cardiopulmonary bypass improves early survival for multivessel coronary artery bypass patients. Ann Thorac Surg 2002;73:1196-203.

Mack MJ. Presidential Address: 4th Annual Meeting of the International Society of Minimally Invasive Cardiac Surgery. What is ISMICS and why does it exist? Heart Surgery Forum 2002;5(1):11-12.

CRSTI Research Protocols

CRSTI currently maintains several protocols with active enrollment. CLICK HERE for a description of current protocols, including sponsors, investigators and designated sites.