The HCA National Disease Management Program for coronary disease detection and treatment in women.

The diagnosis and treatment of heart disease in women continues to be one of the greatest challenges facing cardiovascular medicine today. Marked reductions in mortality rates during the past 2 decades did not result in improved outcomes for women. A major rate-limiting step to improving mortality rates for women is early diagnosis and initiation of effective lifesaving therapies for women. In 1999, HCA Healthcare Systems, Inc, Nashville, TN, initiated a coordinated effort among 208 hospitals in 26 states to improve the diagnosis of coronary disease and to target women who should receive aggressive risk factor modification and referral to cardiologists. We describe the initial phases of program development, including employee risk factor screening; citywide health risk assessment; nationwide educational programs for clinicians, staff, and consumers; and a dedicated outcomes assessment program for tracking women at risk for coronary disease. We believe that these efforts provide a venue for optimal care and improved outcomes for women served by HCA facilities.

Utility of stress echocardiography in the triage of patients with atypical chest pain from the emergency department.

We followed 108 patients presenting to the emergency department with atypical chest pain and triaged with stress echocardiography. One-year cardiac event-free survival was 100% with a negative stress echocardiogram and 25% with a positive study.

Systolic ejection murmurs in the era of modern cardiology: what do we really know?

The basics of pulsatile ejection dynamics are reviewed in order to clarify the relationships among left ventricular and aortic pressures, intra-left ventricular and aortic flow velocities, and cardiovascular sound. The principles of turbulent flow are examined using the Reynolds number concept, and the evidence for cause-and-effect relationships between turbulent flow and murmur generation is presented. Examples of hemodynamics and phonocardiography are given for normal subjects and are compared to patients with aortic stenosis and hypertrophic cardiomyopathy. The concepts presented are used to analyze the results of a new study suggesting increased intraventricular velocities as a new cause for systolic murmurs in adults.

Effects of caregiver specialty on cost and clinical outcomes following hospitalization for heart failure.

In 614 consecutive hospitalizations with the primary discharge diagnosis of diagnosis-related group (DRG) 127 (heart failure and shock), we sought to assess the effect of caregiver specialty (generalist, n = 217; cardiologist, n = 397) on hospital costs, length of stay, and in-hospital mortality. Patients treated by cardiologists were younger (68 vs 71 years) and less likely to have hypertension (52% vs 61%), but were more likely to be men (61% vs 44%), require an intensive care stay (13% vs 5%), have coronary artery disease (49% vs 23%), have a left ventricular ejection fraction <40% (74% vs 49%), and have lower systolic (132 vs 146 mm Hg) and diastolic (76 vs 81 mm Hg) blood pressures on admission. Predictors of acute disease severity were similarly distributed between the 2 groups. No difference was found between patients treated by cardiologists versus those treated by generalists with respect to crude or adjusted hospital cost, length of stay, and in-hospital mortality. However, in subsets of patients who required intensive care during hospitalization (n = 64), as well as those who did not (n = 550), care by cardiologists was associated with a lower adjusted hospital cost. Any potential cost savings that could have accrued from care by cardiologists was, however, negated by the higher proportion of patients treated by cardiologists who required intensive care during hospitalization. We conclude that when differences in clinical variables are adjusted, care by cardiologists versus generalists is associated with similar or lower hospital cost for patients with DRG 127. Our findings challenge the notion that in-patient care provided by specialists is more expensive than that provided by generalists.

Prognostic value of stress echocardiography in the evaluation of atypical chest pain patients without known coronary artery disease.

Patients with atypical chest pain frequently lack significant coronary artery disease (CAD) and are, therefore, at low risk for future adverse cardiovascular events. We hypothesized that in this group of patients, stress echocardiography could identify those at risk for cardiac events. We retrospectively reviewed (mean follow-up 23.0 +/- 7.2 months) the prognostic value of stress echocardiography for major (cardiac death, myocardial infarction, congestive heart failure, and unstable angina) and total (major events plus coronary revascularization) cardiac events in 661 patients with atypical chest pain, normal global left ventricular (LV) systolic function, and no history of CAD. A positive stress echocardiogram was defined as the development of new or worsening wall motion abnormalities with exercise stress (80%) or dobutamine (20%). A total of 41 cardiac and 16 major events were noted. The event-free survival for total cardiac events was 97% for a normal stress echocardiogram and 93% for a normal stress electrocardiogram (ECG) at 30 months. A positive stress ECG predicted an event-free rate of 86% compared with 74% for stress-induced wall motion abnormalities and 42% if stress-induced LV dysfunction accompanied the wall motion abnormalities. A strategy recommending invasive studies based on positive stress echocardiogram results increased the per-patient cost, but led to greater savings per cardiac event predicted and provided incremental prognostic value for future cardiac events beyond clinical and stress electrocardiographic data. Thus, stress echocardiography in low-risk patients for CAD appears to be more cost effective than a stress ECG.

Modulatory impact of cardiac rehabilitation on hyperhomocysteinemia in patients with coronary artery disease and "normal" lipid levels.

In coronary patients with "relatively normal" lipid values and hyperhomocystinemia (levels > or =15 micromol/L), significant 12% reductions in homocysteine levels occurred after cardiac rehabilitation and exercise training. This benefit from cardiac rehabilitation and exercise training may lead to 20% to 30% reductions in overall coronary artery disease risk.

Knowledge of perfusion and contractile reserve improves the predictive value of recovery of regional myocardial function postrevascularization: a study using the combination of myocardial contrast echocardiography and dobutamine echocardiography.

BACKGROUND: This study was designed to determine the value of myocardial contrast echocardiography (MCE) and dobutamine echocardiography (DE), alone or in combination, in predicting functional recovery in patients with resting wall motion abnormalities due to CAD. MCE and DE have been independently shown to be useful in detecting myocardial viability in the post-myocardial infarction setting. METHODS AND RESULTS: Thirty-nine patients with significant coronary artery disease and resting wall motion abnormalities underwent DE (2.5 to 20 microg x kg(-1) x min(-1)) and wall motion analysis (16-segment model). MCE was performed with selective intracoronary injections of sonicated meglumine (2 cm3). Myocardial viability was defined as presence of contrast effect by MCE and contractile reserve or an ischemic response by DE. Functional recovery (improvement in wall motion) was assessed after revascularization (percutaneous transluminal coronary angioplasty, n=20; coronary artery bypass surgery, n=19). When the two groups of patients were analyzed, MCE was associated with excellent sensitivities (84%) yet poor specificities (19% to 26%); DE had lower sensitivities (79% to 80%) but also poor specificities (30% to 36%). The combination of both was associated with excellent sensitivities (90% to 93%) and modest specificities (48% to 50%) for predicting functional recovery. A biphasic response with DE was infrequent (14% to 42%) but highly specific of functional recovery (84% to 94%). MCE had an excellent negative predictive value for functional recovery (83%). CONCLUSIONS: The prediction of functional recovery post-revascularization can be enhanced by combining MCE and DE.

Home inotropic therapy in advanced heart failure: cost analysis and clinical outcomes.

STUDY OBJECTIVES: This study was conducted to assess cost savings and clinical outcomes associated with the use of home i.v. inotropic therapy in patients with advanced (New York Heart Association [NYHA] class IV) heart failure. DESIGN: Retrospective analysis. SETTING: Tertiary care referral center. PATIENTS AND INTERVENTIONS: Twenty-four patients (13 men, 11 women; age, 61+/-12 years) with left ventricular ejection fraction <30% and heart failure refractory to oral agents required home i.v. inotropic therapy for at least 4 consecutive weeks between May 1994 and April 1996. Inotropic agents used included dobutamine (n=20; dose, 5.0+/-2.2 microg/kg/min) or milrinone (n=7; dose, 0.53+/-0.05 microg/kg/min). MEASUREMENTS AND RESULTS: Cost of care and clinical outcomes (hospital admissions, length of hospital stay, NYHA functional class) were compared during the period of inotropic therapy (study period) and the immediate preceding period of equal duration (control period). In comparison to the control period, the study period (3.9+/-2.7 months) was associated with a 16% reduction in cost, amounting to a calculated savings of $5,700 per patient or $1,465 per patient per month. Concomitantly, a decrease in the number of hospital admissions from 2.7+/-2.6 to 1.3+/-1.3 (p=0.056) and length of hospital stay from 20.9+/-12.7 to 5.5+/-5.4 days (p=0.0004) was observed with improvement in NYHA functional class from 4.0+/-0.0 to 2.7+/-0.9 (p<0.0001). Eight patients (38%) died after 2.8+/-1.7 months of home i.v. inotropic therapy. CONCLUSIONS: Home i.v. inotropic therapy reduces hospital admissions, length of stay, and cost of care and improves functional class in patients with advanced (NYHA class IV) heart failure.

Clinical variables affecting recovery of left atrial mechanical function after cardioversion from atrial fibrillation.

OBJECTIVES: We sought to evaluate the effect of clinical factors on recovery of atrial function after cardioversion for atrial fibrillation. BACKGROUND: Lack of effective mechanical atrial function (EMAF) after cardioversion of atrial fibrillation predisposes to thromboembolic complications and delays improvement in functional capacity. METHODS: Fifty-two patients underwent cardioversion (group I, electrical cardioversion, n = 40; group II, pharmacologic or spontaneous cardioversion, n = 12) for atrial fibrillation. Serial transmitral inflow Doppler variables were recorded after cardioversion until EMAF (atrial filling velocity > 0.50 m/s) was seen. Clinical variables (age, duration of atrial fibrillation, left ventricular ejection fraction, left atrial diameter, underlying cardiovascular disease, antiarrhythmic drug therapy and mode of cardioversion) were tested for an association with the outcomes of recovery of atrial function by day 3 and day 7. RESULTS: Effective mechanical atrial function recovered in 68% of patients by day 3 and in 76% by day 7 after cardioversion. The mode of cardioversion was significantly associated with recovery of atrial function by day 3 in bivariate and multivariate analyses (odds ratio 0.12, 95% confidence interval 0.01 to 1.0, for electrical cardioversion). None of the variables had an association with recovery of atrial function by day 7. Group I patients took a longer time to recover atrial function than group II patients (p = 0.012). In addition, group I patients had a significantly lower peak atrial filling velocity (mean [+/-SD] 0.39 +/- 0.19 m/s vs. 0.56 +/- 0.16 m/s) and a higher early filling to atrial filling velocity ratio (2.5 +/- 1.2 vs. 1.5 +/- 0.5) after cardioversion. CONCLUSIONS: A high proportion of patients recover EMAF within 1 week after cardioversion. Patients who undergo electrical cardioversion display a greater degree and a longer duration of mechanical atrial dysfunction than those who convert pharmacologically or spontaneously.

Benefits of reducing the cardiac cycle-triggering frequency of ultrasound imaging to increase myocardial opacification with FSO69 during fundamental and second harmonic imaging.

BACKGROUND: Recent work has shown significant enhancement in myocardial contrast intensity with brief ultrasound pulsing gated to a discrete portion of the cardiac cycle over conventional 30 Hz imaging. We hypothesized that limiting ultrasound imaging to less than every cardiac cycle would further intensity the myocardial echo-contrast effect. We therefore sought to determine the best pulsing frequency for ultrasound imaging to achieve optimal myocardial perfusion after the intravenous administration of FSO69 using fundamental and second harmonic imaging. METHODS AND RESULTS: In 13 male mongrel dogs, myocardial contrast opacification was determined while varying the cardiac cycle-triggering frequency of ultrasound imaging after intravenous injections of FSO69. Resulting myocardial echo-contrast intensities with a cardiac cycle-triggering frequency of every beat during end-diastole were compared with those with a cardiac cycle-triggering frequency of every third and fifth beat. Myocardial opacification, measured by background-subtracted peak intensity and visual scoring, was significantly greater when ultrasound imaging was triggered to every third and fifth beats compared with every beat. These benefits were seen with imaging in both the fundamental and second harmonic modes. Optimal myocardial opacification with FSO69 was achieved with injections as low as 0.1 ml, a dose that produced significant acoustic shadowing in only 24% of the injections. The degree of myocardial opacification was not significantly affected when the images were acquired during end-systole or end-diastole. CONCLUSIONS: Electrocardiogram-gated ultrasound imaging to every third or fifth cardiac cycle greatly improves myocardial opacification compared with imaging each cardiac cycle. This benefit was increased twofold to threefold with the use of second harmonic imaging as compared with fundamental imaging.

Cyclosporine-induced hypertension: evidence for maintained baroreflex circulatory control.

BACKGROUND: The clinical use of cyclosporine as an immunosuppressive agent enhanced long-term survival in transplant recipients at the expense of a high incidence of induced hypertension. Altered neurovegetative (autonomic) cardiovascular control is suspected as a mechanism of this form of hypertension. METHODS: Spectral analysis of systolic arterial pressure and R-R interval variability (electrocardiographic recordings) were performed, and the index alpha of baroreflex gain was computed in four groups of subjects matched for age: 13 orthotopic heart transplant recipients; 13 solid organ transplant recipients; 13 patients with essential hypertension; and 18 control subjects with normal blood pressure. All but the control subjects were treated with similar dihydropyridine calcium entry blockers. Heart and solid organ transplant recipients also received cyclosporine. RESULTS: R-R variance was lowest in the heart transplant recipients. The spectral profile of R-R interval was suggestive of sympathetic predominance in the patients with hypertension, but not in the solid organ transplant recipients or the control subjects. Systolic blood pressure variability and low frequency component (a marker of sympathetic vasomotor modulation) were similar in the four groups. The index alpha was 1.8 +/- 2.2 in heart transplant recipients, 11.7 +/- 6.6 in solid organ transplant recipients, 7.3 +/- 3.6 in patients with hypertension, and 13.5 +/- 6.4 msec/mm Hg in control subjects (p = 0.0001). CONCLUSIONS: These data indicate that (1) cyclosporine-induced hypertension in heart transplant recipients is associated with a loss of baroreflex function as a result of cardiac denervation-related uncoupling; (2) compared with patients with hypertension, organ transplant recipients with hypertension demonstrated a maintained baroreflex function as indicated by a lack of reduction of the index alpha; (3) baroreflex heart rate control in dihydropyridine-treated cyclosporine-induced hypertension is well maintained.

Combination of dobutamine and myocardial contrast echocardiography to differentiate postischemic from infarcted myocardium.

OBJECTIVES: This study tested whether the combination of dobutamine echocardiography (DE) and myocardial contrast echocardiography (MCE) was superior to either technique alone in identifying postischemic myocardium and in differentiating it from necrotic myocardium. BACKGROUND: Wall motion abnormalities at rest occur in postischemic myocardium in the presence of infarction, stunning or hibernation, alone or in combination. Various investigators have suggested that either DE or MCE can be used to identify the presence of myocardial viability. METHODS: We studied a total of 53 mongrel dogs in an open chest model of coronary occlusion of various durations followed by reperfusion and dobutamine administration (10 microg/kg body weight per min). MCE with aortic root injections of Albunex (area under the curve) and DE (percent thickening fraction) were performed at the different stages. Postmortem triphenyltetrazolium chloride (TTC) staining was used to identify myocardial necrosis. RESULTS: Thirteen dogs underwent brief (15 min) occlusions and developed no necrosis (Group I). Of 40 dogs that underwent prolonged (30 to 360 min) occlusions, 14 had no infarction (Group II), whereas 26 did (Group III: 12 papillary muscle, 7 subendocardial, 7 transmural). MCE (expressed as percent change from baseline) demonstrated changes that paralleled the blood flow changes observed by radiolabeled microspheres at all interventions (r = 0.67, p < 0.0001). Regional ventricular function improved with dobutamine administration in the ischemic region in all three groups. The sensitivity (88%) for detecting myocardial viability was superior when the two techniques were combined; however, a poor specificity (61%) was observed. CONCLUSIONS: Contractile reserve and perfusion data are complementary when assessing regional wall motion abnormalities in postischemic myocardium. DE alone cannot differentiate postischemic from infarcted myocardium; simultaneous data on myocardial perfusion are required. The combination of DE and MCE is superior to either technique alone for identifying the absence of myocardial necrosis.

Effects of cardiac rehabilitation and exercise programs on exercise capacity, coronary risk factors, behavior, and quality of life in patients with coronary artery disease.

Previous studies have indicated the benefits of cardiac rehabilitation programs after major coronary artery disease (CAD) events. We studied 591 consecutive patients from two academic institutions before and after completion of a cardiac rehabilitation and exercise training program to determine the effects of this therapy on exercise capacity, indices of obesity, plasma lipid values, behavioral characteristics, and quality of life parameters. After cardiac rehabilitation, statistically significant improvements occurred in exercise capacity (+33%), percent body fat (-6%), body mass index (-1%), HDL-C (+5%), triglycerides (-9%), LDL-C/HDL-C (-6%), anxiety score (-39%), depression score (-35%), somatization score (-37%), and in all parameters of quality of life studied (total +14%). These data further support the ability of cardiac rehabilitation and exercise training programs to improve exercise capacity, plasma lipid values, obesity indices, behavioral characteristics, and quality of life parameters in a large cohort of patients who have had major CAD events.

Myocardial contrast echocardiography: reliable, safe, and efficacious myocardial perfusion assessment after intravenous injections of a new echocardiographic contrast agent.

Reliable and reproducible myocardial opacification after intravenous administration of echocardiographic contrast agents has remained elusive. This study was performed to determine whether a new agent, FS069, a suspension of perfluoropropane-filled albumin microspheres (3.6 microns average microbubble size, concentration 8 x 8(8)/ml), could achieve safe and successful myocardial opacification in open-chest dogs. Seventeen dogs (group 1, n = 7, group 2, n = 10) underwent two-dimensional echocardiography before, during, and after the administration of intravenous FS069. Safety was evaluated by measuring arterial and pulmonary artery pressures, heart rate, blood gases, systolic function, myocardial blood flow, and postmortem analysis of myocardial viability by triphenyl-tetrazolium chloride staining. Efficacy to detect changes in regional myocardial perfusion was assessed by injecting FS069 at baseline, after sequential coronary occlusions and reperfusion, and during intravenous vasodilators with and without coronary occlusions. Results were compared with radiolabeled microspheres. FS069 was found to be safe and effective. In the absence of coronary occlusions, uniform myocardial opacification was observed in all dogs. A perfusion defect was observed in all dogs during coronary occlusions. Background-subtracted peak contrast intensity in the myocardium correctly identified regional myocardial blood flow changes and showed a significant correlation with radiolabeled microspheres (r = 0.65, p = 0.0001).

Myocardial contrast echocardiography in human beings: correlation of resting perfusion defects to sestamibi single photon emission computed tomography.

The presence of myocardial perfusion abnormalities is generally accepted to suggest underlying coronary artery disease. In previous animal studies, myocardial contrast echocardiography (MCE) has been shown to be useful in delineating areas at risk after coronary occlusions. We sought to compare the presence or absence, size, and location of perfusion defects detected in human beings by MCE and sestamibi single photon emission computed tomography (SPECT). Regional wall motion was qualitatively assessed in the parasternal and apical views of a resting two-dimensional echocardiogram. Coronary angiography was performed in all patients and myocardial contrast echocardiography performed with 2 ml of intracoronary sonicated meglumine (Nycomed). A cine loop of the digitized contrast echocardiograms was used to analyze perfusion defects. Gated SPECT resting images in standard views were obtained after technetium 99m sestamibi (20 mCi) was administered. Visually perceived perfusion defects were established at 30% of maximal counts at end diastole. Perfusion defects by both techniques were planimetered, assigned to one of three perfusion artery territories, and expressed as a percentage of the perfusion territory studied. Comparison was made by linear regression analysis. Forty-one patients were studied. Perfusion defects were observed in 12 (29%) patients by MCE, 19 (46%) patients by SPECT, and 11 (27%) patients by both techniques. No perfusion defects were detected by MCE in 29 (70%) patients, by SPECT in 22 (53%) patients, or by either technique in 21 (51%) patients. The two techniques agreed in 78% of the patients. In 67 matching orthogonal views suitable for comparison between the two techniques, an 82% concordance for the presence or absence of defects was observed. The location of the defects matched in 86% of the cases. A significant correlation (p < 0.001; r = 0.62) between these techniques was observed in assessing the size of perfusion defects. In conclusion, our results suggest that MCE and sestamibi SPECT are comparable techniques for detecting severely underperfused myocardium in human beings.

Potential clinical implications of abnormal myocardial perfusion patterns immediately after reperfusion in a canine model: a myocardial contrast echocardiography study.

During myocardial infarction, lack of myocardial opacification after reperfusion has been associated with poor or no recovery of function. We have previously documented the presence of perfusion abnormalities after brief coronary occlusions without infarction and the absence of perfusion abnormalities after prolonged occlusions with infarction. To characterize myocardial perfusion patterns immediately after reperfusion, we studied 53 animals in two groups in a coronary occlusion-reperfusion model. Temporary occlusions (group 1, 15 minutes; group 2, 30 to 360 minutes) were performed, followed by reperfusion with and without dobutamine. Myocardial contrast echocardiography was performed with aortic root injections of sonicated 5% serum human albumin (Albunex) during each intervention. Group 1 dogs showed no evidence of myocardial infarction. In group 2, 26 of 40 dogs had infarctions. After reperfusion, no perfusion abnormalities were seen in 13 of 26 group 2 dogs with infarctions; perfusion abnormalities were identified after reperfusion in 2 of 13 group 1 and in 8 of 14 group 2 dogs without infarctions. In animals subjected to prolonged ischemia, the absence of perfusion abnormalities after reperfusion did not rule out the presence of necrosis. Similarly, in animals without infarction subjected to ischemia, the presence of a perfusion defect after reperfusion did not represent the presence of necrosis but an abnormal microvascular reserve. These results suggest that early after reperfusion, assessment of perfusion by myocardial contrast echocardiography has significant limitations in the evaluation of myocardial viability and salvage.

Ischemia and atherosclerotic coronary artery disease in patients with hypertrophic cardiomyopathy: a review of incidence, pathophysiological mechanisms, clinical implications and management strategies.

Ischemia is suspected to occur frequently in patients with HCM and may result from various mechanisms, for example decreased coronary flow reserve, disease of small intramuscular arteries, "inadequate' size of coronary arteries relative to hypertrophied myocardium, diminution of coronary flow during systole, compression of septal perforator arteries during systole, coronary artery spasm, and co-existent atherosclerotic CAD, which can be present in up to a quarter of HCM patients above 45 years of age. The diagnosis of CAD in patients with HCM is difficult to make on clinical grounds, secondary to the high frequency of angina in patients with HCM without CAD. Pharmacological stress echocardiography is promising but needs to be further studied; stress thallium imaging is beset with frequent false positive results. At this time, coronary angiography remains the only reliable test for the definitive diagnosis of co-existent CAD in HCM. Beta-blockers and verapamil may help in relieving symptoms and silent ischemia in patients with HCM; in those with coexistent CAD and resistant symptoms, CABG alone or in combination with left ventricular myectomy or mitral valve replacement has been recommended.

Adenovirus-mediated in vivo gene transfer in a rabbit model of allograft vasculopathy.

BACKGROUND: The long-term success of heart transplantation continues to be in jeopardy because of the development of accelerated vascular myointimal proliferation. Transfer of genes encoding products that can modulate the adverse consequences of phenomena that cause myointimal proliferation, into the allograft vessel wall, may modify these pathologic processes. The purpose of this study was to assess the feasibility of gene transfer and to evaluate the duration of gene expression in a rabbit heterotopic aortic transplant model of allograft vasculopathy. METHODS: The abdominal aortas of 32 outbred New Zealand rabbits were harvested and cross-sectionally bisected (n = 64). Six donor and recipient animals were used in a preliminary study to examine neointimal proliferation without accompanying gene transfer. Of the remaining 26 rabbits (52 allografts), one half of each allograft aorta was administered a control solution, while the other half was incubated with a replication-defective, recombinant, adenoviral vector-encoding, cytomegalovirus promoter-regulated beta-galactosidase. After a 20-minute incubation period, bilateral aorto-carotid transplantations were performed in 26 recipient rabbits. All animals received cyclosporine immunosuppression (10 mg/kg/day subcutaneously). The allografts were harvested at 3, 7, 10, 21, and 28 days after transplantation and assayed for beta-galactosidase activity. RESULTS: Neointimal areas showed an initially slow increase for the first 10 days, followed by a rapid increase up to 21 days, and tended to plateau thereafter. Significant beta-galactosidase was apparent in aortic sections dissected from host rabbits for all time points, except at 28 days. At the 21-day time point, the aortic section from one rabbit was positive, whereas the other two remained negative. However, the one positive section showed intense beta-galactosidase activity, suggesting variability in the experimental model. At 28 days, all aortic sections were negative. CONCLUSIONS: Our findings confirm that genes delivered by this method are expressed for the duration of early rapid intimal proliferation in this heterotopic rabbit model of aortic allograft vasculopathy. These findings suggest that this animal model can be used to assess the therapeutic potential of gene transfer at the time of vascular transplantation and may provide a novel therapeutic approach to prevent or ameliorate the genesis of allograft vasculopathy.