Coronary Artery Disease: Vetrovec GW

King SB, Aversano T, Ballard WL, Beekman RH, Cowley MJ, Ellis SG, Faxon DP, Hannan EL, Hirshfeld JW, Jacobs AK, Kellett MA, Kimmel SE, Landzberg JS, McKeever LS, Moscucci M, Pomerantz RM, Smith KM, Vetrovec GW, Creager MA, Hirshfeld JW, Holmes DR, Newby LK, Weitz HH, Merli G, Piña I, Rodgers GP, Tracy CM, Anonymous00143, Anonymous00144, Anonymous00145. · No affiliation provided · J Am Coll Cardiol. · Pubmed #17601554 No free full text.

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Anonymous00180, King SB, Aversano T, Ballard WL, Beekman RH, Cowley MJ, Ellis SG, Faxon DP, Hannan EL, Hirshfeld JW, Jacobs AK, Kellett MA, Kimmel SE, Landzberg JS, McKeever LS, Moscucci M, Pomerantz RM, Smith KM, Vetrovec GW, Creager MA, Holmes DR, Newby LK, Weitz HH, Merli G, Piña I, Rodgers GP, Tracy CM. · No affiliation provided · Circulation. · Pubmed #17592076 links to  free full text

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Abbate A, Vetrovec GW. · No affiliation provided · JACC Cardiovasc Interv. · Pubmed #19463350 No free full text.

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Vetrovec GW. · No affiliation provided · Catheter Cardiovasc Interv. · Pubmed #18729175 No free full text.

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Vetrovec GW. · No affiliation provided · Circulation. · Pubmed #15657386 links to  free full text

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Vetrovec GW. · No affiliation provided · J Am Coll Cardiol. · Pubmed #15093866 No free full text.

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Vetrovec GW. · No affiliation provided · Circulation. · Pubmed #10889123 links to  free full text

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Lipinski MJ, Abbate A, Fuster V, Vetrovec GW. · University of Virginia Health System, Department of Internal Medicine, Charlottesville, VA 22908, USA. · Nat Clin Pract Cardiovasc Med. · Pubmed #17380165 No free full text.

Abstract: While 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, also known as statins, have a well-established in role in the treatment and prevention of ischemic coronary artery disease, their utility in the setting of heart failure (HF) and left ventricular (LV) dysfunction remains under investigation. Although a reduction in LDL is the major effect of statin therapy, pleiotropic effects have been demonstrated, which could be responsible for the reduction in morbidity and mortality seen with statin use in patients with HF. Patients with both ischemic and nonischemic HF have been shown to have improved survival with statin therapy, and patients receiving statin therapy are less likely to develop HF. Studies have demonstrated that statins reduce inflammation, improve endothelial function, decrease thrombogenicity, and improve LV and autonomic function. In this Review, we present the literature supporting the pleiotropic effects of statin therapy in patients with HF or LV dysfunction, and discuss the mechanisms by which statins might elicit the improvements in morbidity and mortality seen in these patients.

Lipinski MJ, Fearon WF, Froelicher VF, Vetrovec GW. · Division of Cardiology, Virginia Commonwealth University Health System, Richmond, VA 23298, USA. · J Interv Cardiol. · Pubmed #15491331 No free full text.

Abstract: With increasing research on vulnerable plaques and uncertainty regarding which lesions require revascularization, the goal of this review is to clarify the indications for percutaneous coronary intervention and discuss which lesions do not warrant treatment by intervention. This paper also briefly reviews the potential advantages and limitations of technology that may enable detection of atherosclerotic plaques that are prone to rupture and discusses the future utility of these technologies in prevention of acute coronary syndromes. Providing an evidence-based understanding of lesion morphology and clinical variables that influence outcome enables the interventional cardiologist to determine which atherosclerotic plaques require PCI.

Vetrovec GW, Rizik D, Williard C, Snead D, Piotrovski V, Kopia G. · MCV Hospitals, VCU Health Systems, Richmond, Virginia, USA. · Catheter Cardiovasc Interv. · Pubmed #16342216 No free full text.

Abstract: This study was conducted to assess the systemic drug release and distribution of sirolimus-eluting stents. Early results with sirolimus-eluting stents have demonstrated a favorable outcome for reducing restenosis post coronary intervention. However, the clinical systemic pharmacokinetics of sirolimus released from these stents has not been investigated. Sirolimus-eluting stents (150-178 mcg/18 mm stent) were implanted in 19 patients with coronary artery disease using standard techniques. Blood samples were obtained at multiple times to determine the kinetics of sirolimus release and elimination. Non-compartmental analysis showed that the maximum blood concentration of sirolimus occurred between 3 and 4 hr after implantation, with a peak concentration of 0.57 +/- 0.12 ng/mL (mean +/- SD) and 1.05 +/- 0.39 ng/mL in patients receiving one or two stents, respectively. Terminal-phase elimination half-life was independent of the number of stents and averaged at 213 hr, a value longer than that seen in patients following oral dosing. The apparent clearance was 1.46 +/- 0.45 L/hr with an apparent volume of distribution in the terminal phase of 407 +/- 111 L (data for both stent doses pooled). Minimal measurable blood levels were detectable at 7 days. Peak whole blood level following sirolimus stent implantation in humans is proportional to the number of stents implanted. The prolonged terminal half-life may reflect kinetics of blood clearance combined with continued drug elution and secondary local tissue release.

Abbate A, Salloum FN, Vecile E, Das A, Hoke NN, Straino S, Biondi-Zoccai GG, Houser JE, Qureshi IZ, Ownby ED, Gustini E, Biasucci LM, Severino A, Capogrossi MC, Vetrovec GW, Crea F, Baldi A, Kukreja RC, Dobrina A. · Division of Cardiology/VCU Pauley Heart Center, Virginia Commonwealth University, 1200 E Broad St, West Hospital, 10th Floor, East Wing, Room 1041, PO Box 980281, Richmond, VA 23298-0281, USA. · Circulation. · Pubmed #18474815 links to  free full text

Abstract: BACKGROUND: Experimental interleukin-1 receptor antagonist gene overexpression has shown that interleukin-1 receptor antagonist is cardioprotective during global cardiac ischemia. The aim of the present study was to test the impact of an exogenous recombinant human interleukin-1 receptor antagonist (anakinra) in experimental acute myocardial infarction. METHODS AND RESULTS: Two animal studies were conducted: one of immediate anakinra administration during ischemia in the mouse and one of delayed anakinra administration 24 hours after ischemia in the rat. Seventy-eight Institute of Cancer Research mice and 20 Wistar rats underwent surgical coronary artery ligation (or sham operation) and were treated with either anakinra 1 mg/kg or NaCl 0.9% (saline). Treatment was administered during surgery and then daily for 6 doses in the mice and starting on day 2 daily for 5 doses in the rats. Twenty-eight mice underwent infarct size assessment 24 hours after surgery, 6 saline-treated mice and 22 mice treated with increasing doses of anakinra (1 mg/kg [n=6], 10 mg/kg [n=6], and 100 mg/kg [n=10]); 6 mice were euthanized at 7 days for protein expression analysis. The remaining animals underwent transthoracic echocardiography before surgery and 7 days later just before death. Cardiomyocyte apoptosis was measured in the peri-infarct regions. The antiapoptotic effect of anakinra was tested in a primary rat cardiomyocyte culture during simulated ischemia and in vitro on caspase-1 and -9 activities. At 7 days, 15 of the 16 mice (94%) treated with anakinra were alive versus 11 of the 20 mice (55%) treated with saline (P=0.013). No differences in infarct size at 24 hours compared with saline were observed with the 1- and 10-mg/kg doses, whereas a 13% reduction in infarct size was found with the 100-mg/kg dose (P=0.015). Treatment with anakinra was associated with a significant reduction in cardiomyocyte apoptosis in both the immediate and delayed treatment groups (3.1+/-0.2% versus 0.5+/-0.3% [P<0.001] and 4.2+/-0.4% versus 1.1+/-0.2% [P<0.001], respectively). Compared with saline-treated animals, anakinra-treated mice and rats showed signs of more favorable ventricular remodeling. In vitro, anakinra significantly prevented apoptosis induced by simulated ischemia and inhibited caspase-1 and -9 activities. CONCLUSIONS: Administration of anakinra within 24 hours of acute myocardial infarction significantly ameliorates the remodeling process by inhibiting cardiomyocyte apoptosis in 2 different experimental animal models of AMI. This may open the door for using anakinra to prevent postischemic cardiac remodeling and heart failure.

Abbate A, Bussani R, Liuzzo G, Biondi-Zoccai GG, Barresi E, Mellone P, Sinagra G, Dobrina A, De Giorgio F, Sharma R, Bassan F, Severino A, Baldi F, Biasucci LM, Pandolfi F, Silvestri F, Vetrovec GW, Baldi A, Crea F. · Virginia Commonwealth University, VCU Pauley Heart Center, 1200 E Broad Street, Box 980281, Richmond, VA 23298, USA. · Heart. · Pubmed #17698556 No free full text.

Abstract: BACKGROUND: T-lymphocyte activation within atherosclerotic plaque, and widespread to the myocardium, has been shown in patients with acute coronary syndromes. OBJECTIVE: To investigate the presence of T-lymphocyte infiltrate at different stages of acute coronary syndromes by studying patients with sudden coronary death, acute myocardial infarction (AMI) and healed infarction, in comparison with patients with myocarditis and patients with non-ischaemic heart failure. METHODS: 72 cases were studied at autopsy: 12 dying of sudden coronary death (group 1), 12 dying <4 weeks (group 2) and 12 dying >4 months after AMI (group 3), 12 with active lymphocytic myocarditis (group 4), 12 with hypertensive heart disease (group 5), and 12 control subjects (group 6). Light microscopy was performed to measure the number of activated T-lymphocytes (CD3+/DR+) in the myocardium and coronary artery wall, and intercellular adhesion molecule-1 (ICAM-1) expression in the myocardium. RESULTS: Activated T-lymphocyte infiltrates and ICAM-1 myocardial expression in both remote and peri-infarction regions and activated T-lymphocytes within the epicardial coronary artery wall of both the infarct- and non-infarct-related arteries were found in groups 1, 2 and 3, whereas myocardial, but not coronary, infiltrates were found in groups 4 (p<0.001 vs groups 1, 2 and 3 for coronary infiltrates). Groups 5 and 6 had no evidence of myocardial or coronary inflammation (p<0.001 vs groups 1, 2 and 3). CONCLUSIONS: The study shows the presence of a lymphocytic infiltrate in both coronary arteries and myocardium and a proinflammatory phenotype shift in the myocardium associated with acute coronary thrombosis in patients dying suddenly, shortly, or even late after coronary thrombosis.

Lipinski MJ, Martin RE, Cowley MJ, Goudreau E, Malloy WN, Johnson RE, Vetrovec GW. · Division of Cardiology, Virginia Commonwealth University Health Systems, Richmond 23298-0036, USA. · Clin Cardiol. · Pubmed #16477776 No free full text.

Abstract: BACKGROUND: While morbidity and mortality were shown to be increased in the setting of an elevated white blood cell (WBC) count for patients with acute coronary syndrome, the impact of statin therapy on mortality for patients with an elevated WBC count is unknown in high-risk patients with coronary artery disease. HYPOTHESIS: The goal of this study was to determine whether statin therapy improved survival in patients with elevated WBC count undergoing percutaneous coronary intervention (PCI) with preexisting left ventricular (LV) dysfunction, a population at high risk for adverse outcomes. METHODS: We retrospectively evaluated consecutive patient procedures performed at our institution from 1996 through 1999. Patients had a technically adequate angiographic left ventriculogram with a calculated ejection fraction (EF) < or = 50%. Patients with prior coronary artery bypass graft were excluded. Mortality data were retrieved using the U.S. Social Security Death Index. Follow-up ranged from 3.5 to 6.5 years. Means are provided with +/- standard deviation, and p values < 0.05 were considered significant. RESULTS: Of the study population of 238 patients (average EF 39 +/- 9.8%, mean age 57.5 +/- 12 years, 68% men) 61% underwent PCI for a recent myocardial infarction, 68% received stents, and 65% were discharged on statins. Mean WBC count was 9,000 +/- 3,100 cells/mm3, with 28% of patients having a WBC > or = 10,000 cells/mm3. During follow-up, 27% of our population died. Patients with a WBC > or = 10,000 had worse survival than patients with WBC < 10,000 (1-year survival: 86 vs. 96%, p < 0.05; 3-year survival: 79 vs. 89%, p < 0.05). Survival was significantly improved in patients on statin therapy regardless of WBC count, but the greatest benefit tended to be in patients with WBC > or = 10,000 (WBC > or = 10,000; odds ratio [OR] 5.14, 95% confidence interval [CI] 1.44-19.0, WBC < 10,000; OR 2.79,95% CI 1.13-7.1). Proportional hazard regression analysis demonstrated that both statin therapy and WBC count predicted mortality. CONCLUSION: Patients undergoing PCI with LV dysfunction discharged on statins had improved survival regardless of WBC count, with a trend for greater improvement in patients with elevated WBC counts. In addition, WBC count predicts mortality in this high-risk population with LV dysfunction undergoing PCI.

Lipinski MJ, Vetrovec GW, Gorelik D, Froelicher VF. · Division of Cardiology, Veterans Affairs Palo Alto Health Care System, Stanford University, Palo Alto, California 94304, USA. · J Card Fail. · Pubmed #16230267 No free full text.

Abstract: BACKGROUND: The ability to better predict outcome with exercise testing in patients with heart failure (HF) and left ventricular systolic dysfunction (LVSD) may prove extremely valuable in determining which patients are at increased risk. This study evaluated the ability of heart rate recovery (HRR) to predict outcome in patients with HF and validate previous findings in LVSD. METHODS AND RESULTS: HRR was measured at 1-, 2-, 3-, and 5-minute time points after treadmill testing in 2,193 males being evaluated for chest pain at the Palo Alto and Long Beach VA Hospitals. Left ventricular ejection fraction (LVEF) was calculated using biplane ventriculography and patients were considered to have LVSD if they had an LVEF <50%. Angiographic and clinical data was available for all patients. Of the 2,193 patients, 314 patients had LVSD and 109 had a history of HF. Both HF patients and patients with LVSD with a normal HRR at 2 minutes had improved survival compared with patients that had an abnormal HRR at 2 minutes when adjusted for age and beta-blocker use (HF adjusted odds ratio 0.25, 95% CI 0.10-0.66, P < .006; LVSD alone adjusted odds ratio 0.25, 95% CI 0.13-0.47, P < .0001). Stepwise proportional hazard regression analysis revealed that only 2-minute HRR, age, LVEF, and chronic obstructive pulmonary disorder were significant predictors of mortality in patients with LVSD and only HRR at 2 minutes and LV hypertrophy were significant predictors of mortality in patients with HF. CONCLUSION: HRR is a significant predictor of mortality in patients with HF and patients with LVSD and may be useful in better determining prognosis.

Lipinski MJ, Martin RE, Cowley MJ, Goudreau E, Malloy WN, Vetrovec GW. · Division of Cardiology, Virginia Commonwealth University Medical Center, Richmond, Virginia. · Catheter Cardiovasc Interv. · Pubmed #16216018 No free full text.

Abstract: While earlier studies of balloon angioplasty (BA) in patients with left ventricular (LV) dysfunction suggested high late mortality, a study directly comparing coronary stenting and BA has not been performed. Since stenting provides a more durable revascularization, we sought to compare long-term survival in patients undergoing stenting vs BA in patients with decreased left ventricular ejection fractions (LVEF). We evaluated consecutive patient procedures performed in our institution from 1996 through 1999. Patients were considered part of the stent group if they received at least one stent. To be included, patients had to have a technically adequate angiographic LV gram with a calculated LVEF<or=50%. Patients with prior CABG were excluded. Mortality data was retrieved using the United States Social Security Death Index. Follow-up ranged from 3.5 to 6.5 years. Statistical analysis was performed and tests were significant with a P-value<0.05. A total of 238 patients fulfilled our criteria. Mean age was 57.5+/-12 years, mean LVEF was 39+/-10%, 67% were males, 71.5% received stents, 62% had a recent MI, and 19% died during follow-up. Overall 5-year survival was 84% for stenting and 77% for BA (P=NS). Patients with an LVEF<or=40% (n=110) had better survival at 5 years if they received a stent compared with BA alone (76% for stents vs. 53% for BA; P<0.05). Stenting was found to be significant predictor of late survival on Cox Hazard Regression analysis in patients with an LVEF<or=50% and LVEF<or=40%. This study demonstrates improved 5-year survival for patients undergoing stenting compared with balloon angioplasty in patients with LVEF<or=40%.

Lipinski MJ, Vetrovec GW, Froelicher VF. · Cardiology Division, Veterans Affairs Palo Alto Health Care System, Stanford University, CA 94304, USA. · Am J Cardiol. · Pubmed #14969619 No free full text.

Abstract: We retrospectively analyzed exercise treadmill and coronary angiographic data of 2,193 men to compare heart rate (HR) recovery with angiographic and mortality data during a follow-up study of 7 +/- 2.7 years. Only the first 2 minutes of HR recovery predicted mortality (p <0.001), and the HR decrease during the second minute of recovery predicted the presence of coronary artery disease (p <0.05).

Krishnaswami A, Carr ME, Jesse RL, Kontos MC, Minisi AJ, Ornato JP, Vetrovec GW, Martin EJ. · Department of Internal Medicine, Medical College of Virginia Hospitals of Virginia Commonwealth University, Richmond, Virginia, USA. · Thromb Haemost. · Pubmed #12428087 No free full text.

Abstract: Rapid laboratory markers that correlate with patient risk would facilitate the decision making regarding admission of patients with chest pain (CP). Platelet contractile force (PCF) and clot elastic modulus (CEM) are elevated in patients undergoing coronary bypass grafting. This study assessed PCF, CEM, and platelet aggregation in patients presenting to the emergency department with chest pain (CP). Results were compared with fifty normal controls. Both the total group of CP patients (n = 100) and the subset of patients (n = 36) with documented coronary artery disease (CAD) had significantly elevated PCF and CEM, and significantly decreased platelet aggregation relative to normal (p <0.001 for the total group, p </=0.008 for patients with CAD). Patients with electrocardiographic evidence of ischemia had the highest PCF and CEM values of any patient group. Increased PCF and CEM were not due to higher platelet counts, and PCF did not differ by race.

Thomas WJ, Cowley MJ, Vetrovec GW, Malloy W, Goudreau E. · Division of Cardiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298, USA. · Am J Cardiol. · Pubmed #10867099 No free full text.

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Topaz O, Cowley MJ, Mohanty PK, Vetrovec GW. · Cardiac Catheterization Laboratories, McGuire VA Medical Center and Medical College of Virginia Hospitals, Medical College of Virginia, Virginia Commonwealth University, Richmond 23249, USA. · Catheter Cardiovasc Interv. · Pubmed #10348551 No free full text.

Abstract: Accelerated allograft vasculopathy significantly limits the survival of heart transplant recipients. The prevalence of allograft coronary artery disease is as high as 18% by 1 year and 50% by 5 years following heart transplant. Heart failure and sudden cardiac death are the two most common clinical presentations. In heart transplant recipients with severe, discrete focal allograft vascular disease, percutaneous balloon angioplasty is a viable palliative option. However, its application is limited by a significant restenosis rate and progression of allograft disease in nontreated segments. Diffuse disease with tapering of vessels may be approached by debulking devices. Emerging revascularization modalities for focal stenoses and some of the diffuse tapering vessels include coronary stents, rotational atherectomy, various wavelength lasers, and, to a lesser extent, directional atherectomy. Conceivably, stents will reduce restenosis rates related to focal, discrete plaques; yet it is unknown whether they will be efficacious in short- and long-term treatment of diffusely diseased segments affected by allograft disease. Accurate assessment of clinical outcomes and long-term evaluation is imperative prior to acceptance of these devices as fundamental interventional tools for treatment of allograft coronary artery disease.

Thomas WJ, Moskowitz WB, Freedman A, Vetrovec GW, Goudreau E. · Division of Cardiology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA. · Catheter Cardiovasc Interv. · Pubmed #10216016 No free full text.

Abstract: Percutaneous therapeutic embolization may be an effective strategy to manage distal coronary perforations or inadvertent iatrogenic coronary arteriovenous fistula complicating revascularization procedures. We present two cases in which embolization techniques were used to manage these patients and avoid the need for surgical intervention.

Abbate A, Morales C, De Falco M, Fedele V, Biondi Zoccai GG, Santini D, Palleiro J, Vasaturo F, Scarpa S, Liuzzo G, Severino A, Baldi F, Crea F, Biasucci LM, Vetrovec GW, Gelpi RJ, Baldi A. · No affiliation provided · Int J Cardiol. · Pubmed #17112609 No free full text.

Abstract: Apoptosis is a pathologic feature of cardiomyocytes in acute myocardial infarction (AMI) and heart failure. The temporal course of apoptosis in the peri-infarct area in the weeks following an AMI is still uncompletely defined. In order to study the time course of apoptosis after AMI, 16 rabbits underwent left coronary artery ligation and were sacrificed at 16, 26, 35, and 56 days after surgery. Increased apoptotic rate (AR) was observed at in the peri-infarct region than in remote myocardium (5.4% [2.5-9.6] vs 0.4% [0.1-0.9], respectively, P<0.001) and than in sham-operated cases (0.01% [0-0.02], P<0.001). A gradual decrease of AR in the peri-infarct region was observed over time with a 90% reduction at 8 weeks after coronary ligation.