Search PubMed⌕ Search

Biomedical subjects

R O Bonow

Publications and source records attributed to R O Bonow.

At least 19 recordsLinked to original sources
PubMed2005

Atorvastatin inhibits calcification and enhances nitric oxide synthase production in the hypercholesterolaemic aortic valve.

OBJECTIVE: To study in a rabbit model the expression of endothelial nitric oxide synthase (eNOS) in association with the development of calcification of the aortic valve, and to assess the effects of atorvastatin on eNOS expression, nitrite concentration, and aortic valve calcification. METHODS: Rabbits (n = 48) were treated for three months: 16, forming a control group, were fed a normal diet; 16 were fed a 0.5% (wt/wt) high cholesterol diet; and 16 were fed a 0.5% (wt/wt) cholesterol diet plus atorvastatin (2.5 mg/kg/day). The aortic valves were examined with eNOS immunostains and western blotting. Cholesterol and high sensitivity C reactive protein (hsCRP) concentrations were determined by standard assays. Serum nitrite concentrations were measured with a nitric oxide analyser. eNOS was localised by electron microscopy and immunogold labelling. Calcification in the aortic valve was evaluated by micro-computed tomography (CT). RESULTS: Cholesterol, hsCRP, and aortic valve calcification were increased in the cholesterol fed compared with control animals. Atorvastatin inhibited calcification in the aortic valve as assessed by micro-CT. eNOS protein concentrations were unchanged in the control and cholesterol groups but increased in the atorvastatin treated group. Serum nitrite concentrations were decreased in the hypercholesterolaemic animals and increased in the group treated with atorvastatin. CONCLUSION: These data provide evidence that chronic experimental hypercholesterolaemia produces bone mineralisation in the aortic valve, which is inhibited by atorvastatin.

Animals↗
PubMed2001

Predictors of long-term outcomes following direct percutaneous coronary intervention for acute myocardial infarction.

To determine predictors of a long-term major adverse cardiac event (MACE) in unselected patients undergoing direct percutaneous coronary intervention (PCI), 274 consecutive patients presenting within 12 hours of ST-segment elevation acute myocardial infarction (AMI) were evaluated. No patient with ST-segment elevation AMI received intravenous thrombolytic drugs. Chest pain to balloon time was 3.8 hours (range 2.5 to 6.9). percutaneous transluminal coronary angioplasty was successful in 95% of patients. Abciximab was administered to 69% of patients, stents were deployed in 53%, and 17% underwent only catheterization. In-hospital events were death (7%), abrupt closure (2%), emergent coronary artery bypass grafting (CABG) (5%), repeat PCI (3%), and recurrent myocardial infarction (1%). In patients undergoing direct PCI (n = 227), the in-hospital event rate was death 5.3%, abrupt closure 2.2%, emergency CABG 0.9%, repeat PCI 3.1%, and repeat myocardial infarction 1.3%. Median time to last follow-up or death was 20 months (range 11 to 34), and to any event, 0.3 months (range 0.03 to 24.0). Postdischarge MACE included death (5%), AMI (4%), repeat PCI (8%), CABG (9%), and stroke (0.7%). Among those undergoing direct PCI (n = 227), 10% died, 3.5% had a repeat AMI, 9% had a repeat PCI, 5% had CABG, and 1% had a stroke at long-term follow-up. At long-term follow-up, 75% were event free. Multivariate predictors were (hazard ratio [95% confidence interval (CI)]): abciximab use 0.6 (95% CI 0.43 to 0.95), Killip class 2.2 (95% CI 1.1 to 4.4), and number of narrowed coronary arteries 1.7 (95% CI 1.4 to 2.2). In this unselected consecutive series of patients presenting with ST-segment elevation AMI, direct PCI was associated with sustained long-term efficacy. Outcomes were predicted by cardiac impairment at presentation and number of narrowed coronary arteries. MACE is not related to device selection but is significantly improved with abciximab.

Abciximab↗
PubMed2001

Improvement in hypertension in patients with diabetes mellitus after kidney/pancreas transplantation.

BACKGROUND: Hypertension persists in many patients with diabetes mellitus after kidney transplantation. However, the impact of control of diabetes as well as kidney failure on hypertension by combined kidney and pancreas transplantation has not been studied. METHODS AND RESULTS: Between March 1993 and August 1998, 111 patients with type 1 diabetes mellitus underwent successful pancreas transplantation (108 kidney/pancreas transplantation) and another 28 patients with type 1 diabetes mellitus underwent isolated kidney transplantation. Blood pressure measurements and all antihypertensive medications were determined for both groups before transplantation and at 1, 3, 6, and 12 months and at the most recent outpatient evaluation after transplantation. At baseline, the mean blood pressure was 151/88 and 151/83 mm Hg for the kidney/pancreas and isolated kidney transplant patients, respectively. The mean blood pressure decreased to 134/77 mm Hg 1 month after kidney/pancreas transplantation (P<0.001) and decreased further to 126/70 mm Hg (P<0.001) at a mean follow-up of 18 months. This reduction in blood pressure after transplantation occurred despite a decrease in antihypertensive medications and the institution of immunosuppressive agents. At 1 month after kidney/pancreas transplantation, the average number of antihypertensive medications per patient was 0.9+/-1.0, compared with 2.5+/-1.1 before surgery (P<0.001). At 18 months after transplantation, 34% of patients were both normotensive (blood pressure </=130/85 mm Hg) and receiving no antihypertensive medications. In contrast, there was no significant decrease in systolic blood pressure or antihypertensive medication use in the patients receiving an isolated kidney transplant. CONCLUSIONS: Successful kidney/pancreas transplantation results in a marked improvement in hypertension treatment that is not observed in patients undergoing isolated kidney transplantation. These data underscore the importance of diabetes in the pathogenesis of hypertension in patients with diabetes and kidney failure.

Adult↗
PubMed2001

Visualization of discrete microinfarction after percutaneous coronary intervention associated with mild creatine kinase-MB elevation.

BACKGROUND: Mild elevations in creatine kinase-MB (CK-MB) are common after successful percutaneous coronary interventions and are associated with future adverse cardiac events. The mechanism for CK-MB release remains unclear. A new contrast-enhanced MRI technique allows direct visualization of myonecrosis. METHODS AND RESULTS: Fourteen patients without prior infarction underwent cine and contrast-enhanced MRI after successful coronary stenting; 9 patients had procedure-related CK-MB elevation, and 5 did not (negative controls). The mean age of all patients was 61 years, 36% had diabetes, 43% had multivessel coronary artery disease, and all had a normal ejection fraction. Twelve patients (86%) received an intravenous glycoprotein IIb/IIIa inhibitor; none underwent atherectomy, and all had final TIMI 3 flow. Of the 9 patients with CK-MB elevation, 5 had a minor side branch occlusion during stenting, 2 had transient ECG changes, and none developed Q-waves. The median CK-MB was 21 ng/mL (range, 12 to 93 ng/mL), which is 2.3x the upper limit of normal. Contrast-enhanced MRI demonstrated discrete regions of hyperenhancement within the target vessel perfusion territory in all 9 patients. Only one developed a new wall motion abnormality. The median estimated mass of myonecrosis was 2.0 g (range, 0.7 to 12.2 g), or 1.5% of left ventricular mass (range, 0.4% to 6.0%). Hyperenhancement persisted in 5 of the 6 who underwent a repeat MRI at 3 to 12 months. No control patient had hyperenhancement. CONCLUSIONS: Contrast-enhanced MRI provides an anatomical correlate to biochemical evidence of procedure-related myocardial injury, despite the lack of ECG changes or wall motion abnormalities. Mild elevation of CK-MB after percutaneous coronary intervention is the result of discrete microinfarction.

Adult↗
PubMed2001

Comparison of endocardial electromechanical mapping with radionuclide perfusion imaging to assess myocardial viability and severity of myocardial ischemia in angina pectoris.

The assessment of left ventricular electromechanical activity using a novel, nonfluoroscopic 3-dimensional mapping system demonstrates considerable differences in electrical and mechanical activities within regions of myocardial infarction or ischemia. We sought to determine whether these changes correlate with indexes of myocardial perfusion, viability, or ischemia. A 12-segment comparative analysis was performed in 61 patients (45 men, 61 +/- 12 years old) with class III to IV angina, having reversible and/or fixed myocardial perfusion defects on single-photon emission computed tomographic perfusion imaging. A dual-isotope protocol was used, consisting of rest and 4-hour redistribution thallium images followed by adenosine technetium-99m sestamibi imaging. Average rest endocardial unipolar voltage (UpV) and local shortening (LS) mapping values were compared with visually derived perfusion scores. There was gradual and proportional reduction in regional UpV and LS in relation to thallium-201 uptake score at rest (p = 0.0001 and p = 0.0002, respectively) and redistribution studies (p = 0.0001 and p = 0.003, respectively). UpV > or = 7.4 mV and LS > or = 5.0% had a sensitivity of 78% and 65%, respectively, with a specificity of 68% and 67% for detecting viable myocardium. UpV values of 12.3 and 5.4 mV had 90% specificity and sensitivity, respectively, to predict viable tissue. UpV, but not LS, values differentiated between normal segments and those with adenosine-induced severe perfusion defects (11.8 +/- 5.3 vs 8.8 +/- 4.1 mV, p = 0.005). Catheter-based left ventricular assessment of electromechanical activity correlates with the degree of single-photon emission computed tomographic perfusion abnormality and can identify myocardial viability with a greater accuracy than myocardial ischemia.

Adenosine↗
PubMed2001

Visualisation of presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction.

BACKGROUND: A technical advance in contrast-enhanced magnetic resonance imaging (MRI) has significantly improved image quality. We investigated whether healed myocardial infarction can be visualised as hyperenhanced regions with this new technique, and whether assessment of the transmural extent of infarction yields new physiological data. METHODS: 82 MRI examinations were carried out in three groups: patients with healed myocardial infarction; patients with non-ischaemic cardiomyopathy; and healthy volunteers. Patients with healed myocardial infarction were prospectively enrolled after enyzmatically proven necrosis and imaged 3 months (SD 1) or 14 months (7) later. The MRI procedure used a segmented inversion-recovery gradient-echo sequence after gadolinium administration. Findings were compared with those of coronary angiography, electrocardiography, cine MRI, and creatine kinase measurements. FINDINGS: 29 (91%) of 32 patients with infarcts imaged at 3 months (13 non-Q-wave) and all of 19 imaged at 14 months (eight non-Q-wave) showed hyperenhancement. In patients in whom the infarct-related-artery was identified by angiography, 24 of 25 imaged at 3 months and all of 14 imaged at 14 months had hyperenhancement in the appropriate territory. None of the 20 patients with non-ischaemic cardiomyopathy or the 11 healthy volunteers showed hyperenhancement. Irrespective of the presence or absence of Q waves, the majority of patients with hyperenhancement had only non-transmural involvement. Normal left-ventricular contraction was shown in seven patients examined at 3 months and three examined at 14 months, but in these cases hyperenhancement was limited to the subendocardium. INTERPRETATION: The presence, location, and transmural extent of healed Q-wave and non-Q-wave myocardial infarction can be accurately determined by contrast-enhanced MRI.

Adult↗
PubMed2001

Relative lymphocyte count: a prognostic indicator of mortality in elderly patients with congestive heart failure.

BACKGROUND: A reduction in the relative lymphocyte count is a marker of the stress response; however, its prognostic value remains undetermined. The objective of this study was to investigate the predictive value of the relative lymphocyte count for survival in elderly patients with congestive heart failure (CHF). METHODS AND RESULTS: One thousand two hundred seventy-four consecutive patients above the age of 65 years hospitalized with heart disease were enrolled in the CHF Italian Study and followed up for 3 years. Of these, 413 patients were excluded because of factors that could affect the lymphocyte count. Of the remaining 861 patients, 423 (49%) met the criteria for the diagnosis of CHF (mean age 76 +/- 7 years, 51% men), of whom 162 patients (38%) had a relative lymphocyte count < or = 20%. The 3-year all-cause mortality in patients with CHF and a relative lymphocyte count < or = 20% was 64% compared with 40% in patients with a relative lymphocyte count > 20% (P < .0001). The age- and sex-adjusted hazard ratio for death in patients with CHF and low relative lymphocyte count was 1.76 (95% confidence interval 1.34-2.32, P = .0001). After adjustment for baseline differences and variables associated with or known to affect lymphocyte count, the hazard ratio remained significantly different from 1.0 (hazard ratio 1.73, 95% confidence interval 1.21-2.48, P = .0026). CONCLUSION: A low relative lymphocyte count is an independent marker of poor prognosis in elderly patients with CHF. The relative lymphocyte count is a simple, accurate, widely available, and inexpensive marker that can help to identify elderly patients with CHF who are at increased risk for mortality. The pathophysiologic mechanism of this observation remains to be determined.

Aged↗
PubMed2001

Intracoronary administration of recombinant human vascular endothelial growth factor to patients with coronary artery disease.

BACKGROUND: Patients with severe myocardial ischemia who are not candidates for percutaneous or surgical revascularization have few therapeutic options. Therapeutic angiogenesis in animal models with use of recombinant human vascular endothelial growth factor (rhVEGF) has resulted in successful revascularization of ischemic myocardium. This was a dose escalation trial designed to determine the safety and tolerability of intracoronary rhVEGF infusions. METHODS AND RESULTS: Patients were eligible if they had stable exertional angina, a significant reversible perfusion defect by stress myocardial perfusion study, and coronary anatomy that was suboptimal for percutaneous coronary intervention or coronary artery bypass grafting. rhVEGF was administered to a total of 15 patients by 2 sequential (eg, right and left) intracoronary infusions, each for 10 minutes, at rates of 0.005 (n = 4), 0.017 (n = 4), 0.050 (n = 4), and 0.167 mg/kg/min (n = 3). Pharmacokinetic sampling and hemodynamic monitoring were performed for 24 hours. Radionuclide myocardial perfusion imaging was performed before treatment and at 30 and 60 days after treatment. Follow-up angiograms were performed on selected patients at 60 days. The maximally tolerated intracardiac dose of rhVEGF was 0.050 mg/kg/min. Minimal hemodynamic changes were seen at 0.0050 mg/kg/min (2% +/- 7% [SD] mean decrease in systolic blood pressure from baseline to nadir systolic blood pressure), whereas at 0.167 mg/kg/min there was a 28% +/- 7% mean decrease from baseline to nadir (136 to 95 mm Hg systolic). Myocardial perfusion imaging was improved in 7 of 14 patients at 60 days. All 7 patients with follow-up angiograms had improvements in the collateral density score. CONCLUSION: rhVEGF appears well tolerated by coronary infusion at rates up to 0.050 mg/kg/min. This study provides the basis for future clinical trials to assess the clinical benefit of therapeutic angiogenesis with rhVEGF.

Coronary Circulation↗
PubMed2000

The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction.

BACKGROUND: Recent studies indicate that magnetic resonance imaging (MRI) after the administration of contrast material can be used to distinguish between reversible and irreversible myocardial ischemic injury regardless of the extent of wall motion or the age of the infarct. We hypothesized that the results of contrast-enhanced MRI can be used to predict whether regions of abnormal ventricular contraction will improve after revascularization in patients with coronary artery disease. METHODS: Gadolinium-enhanced MRI was performed in 50 patients with ventricular dysfunction before they underwent surgical or percutaneous revascularization. The transmural extent of hyperenhanced regions was postulated to represent the transmural extent of nonviable myocardium. The extent of regional contractility at the same locations was determined by cine MRI before and after revascularization in 41 patients. RESULTS: Contrast-enhanced MRI showed hyperenhancement of myocardial tissue in 40 of 50 patients before revascularization. In all patients with hyperenhancement the difference in image intensity between hyperenhanced regions and regions without hyperenhancement was more than 6 SD. Before revascularization, 804 of the 2093 myocardial segments analyzed (38 percent) had abnormal contractility, and 694 segments (33 percent) had some areas of hyperenhancement. In an analysis of all 804 dysfunctional segments, the likelihood of improvement in regional contractility after revascularization decreased progressively as the transmural extent of hyperenhancement before revascularization increased (P<0.001). For instance, contractility increased in 256 of 329 segments (78 percent) with no hyperenhancement before revascularization, but in only 1 of 58 segments with hyperenhancement of more than 75 percent of tissue. The percentage of the left ventricle that was both dysfunctional and not hyperenhanced before revascularization was strongly related to the degree of improvement in the global mean wall-motion score (P<0.001) and the ejection fraction (P<0.001) after revascularization. CONCLUSIONS: Reversible myocardial dysfunction can be identified by contrast-enhanced MRI before coronary revascularization.

Contrast Media↗
PubMed2000

Clinical trials in coronary angiogenesis: issues, problems, consensus: An expert panel summary.

The rapid development of angiogenic growth factor therapy for patients with advanced ischemic heart disease over the last 5 years offers hope of a new treatment strategy based on generation of new blood supply in the diseased heart. However, as the field of therapeutic coronary angiogenesis is maturing from basic and preclinical investigations to clinical trials, many new and presently unresolved issues are coming into focus. These include in-depth understanding of the biology of angiogenesis, selection of appropriate patient populations for clinical trials, choice of therapeutic end points and means of their assessment, choice of therapeutic strategy (gene versus protein delivery), route of administration, and the side effect profile. The present article presents a summary statement of a panel of experts actively working in the field, convened by the Angiogenesis Foundation and the Angiogenesis Research Center during the 72nd meeting of the American Heart Association to define and achieve a consensus on the challenges facing development of therapeutic angiogenesis for coronary disease.

Angiogenesis Inducing Agents↗
PubMed2000

Short- and intermediate-term clinical outcomes from direct myocardial laser revascularization guided by biosense left ventricular electromechanical mapping.

BACKGROUND: Direct myocardial revascularization (DMR) has been examined as an alternative treatment for patients with chronic refractory myocardial ischemic syndromes who are not candidates for conventional coronary revascularization. Methods and Results-We used left ventricular electromagnetic guidance in 77 patients with chronic refractory angina (56 men, mean age 61+/-11 years, ejection fraction 0.48+/-0.11) to perform percutaneous DMR with an Ho:YAG laser at 2 J/pulse. Procedural success (laser channels placed in prespecified target zones) was achieved in 76 of 77 patients with an average of 26+/-10 channels (range 11 to 50 channels). The rate of major in-hospital cardiac adverse events was 2.6%, with no deaths or emergency operations, 1 patient with postprocedural pericardiocentesis, and 1 patient with minor embolic stroke. The rate of out-of-hospital adverse cardiac events (up to 6 months) was 2.6%, with 1 patient with myocardial infarction and 1 patient with stroke. Exercise duration after DMR increased from 387+/-179 to 454+/-166 seconds at 1 month and to 479+/-161 seconds at 6 months (P=0.0001). The time to onset of angina increased from 293+/-167 to 377+/-176 seconds at 1 month and to 414+/-169 seconds at 6 months (P=0.0001). Importantly, the time to ST-segment depression (>/=1 mm) also increased from 327+/-178 to 400+/-172 seconds at 1 month and to 436+/-175 seconds at 6 months (P=0.001). Angina (Canadian Cardiovascular Society classification) improved from 3.3+/-0.5 to 2.0+/-1.2 at 6 months (P<0.001). Nuclear perfusion imaging studies with a dual-isotope technique, however, showed no significant improvements at 1 or 6 months. CONCLUSIONS: Percutaneous DMR guided by left ventricular mapping is feasible and safe and reveals improved angina and prolonged exercise duration for up to a 6-month follow-up.

Adult↗
PubMed2000

Effect of intracoronary recombinant human vascular endothelial growth factor on myocardial perfusion: evidence for a dose-dependent effect.

BACKGROUND: Animal models of therapeutic angiogenesis have stimulated development of clinical application in patients with limited options for coronary revascularization. The impact of recombinant human vascular endothelial growth factor (rhVEGF) on myocardial perfusion in humans has not been reported. METHODS AND RESULTS: Fourteen patients underwent exercise (n=11), dobutamine (n=2), or dipyridamole (n=1) myocardial perfusion single photon emission CT (SPECT) before as well as 30 and 60 days after rhVEGF administration. After uniform processing and display, 2 observers blinded to the timing of the study and dose of rhVEGF reviewed the SPECT images. By a visual, semiquantitative 20-segment scoring method, summed stress scores (SSS) and summed rest scores (SRS) were generated. Although the SSS did not change from baseline to 30 days (21.6 versus 21.5; P=NS), the SRS improved after rhVEGF (13.2 versus 10.4; P<0.05). Stress and rest perfusion improved in >2 segments infrequently in patients treated with low-dose rhVEGF. However, 5 of 6 patients had improvement in >2 segments at rest and stress with the higher rhVEGF doses. Furthermore, although neither the SSS nor the SRS changed in patients treated with the low doses, the SRS decreased in the high-dose rhVEGF patients at 60 days (14.7 versus 10.7; P<0.05). Quantitative analysis was consistent with the visual findings but failed to demonstrate statistical significance. CONCLUSIONS: Although not designed to demonstrate rhVEGF efficacy, these phase 1 data support the concept that rhVEGF improves myocardial perfusion at rest and provide evidence of a dose-dependent effect.

Cardiotonic Agents↗
PubMed2000

Left ventricular apical thrombus and myocardial viability: a dobutamine stress echocardiographic study.

The objective of this article was to determine whether the presence of left ventricular apical thrombus is a marker of nonviable myocardium. Reduced coronary blood flow secondary to atherosclerosis may result in chronic reversible left ventricular wall-motion abnormalities. Severe regional abnormalities also predispose to formation of left ventricular thrombus. The relationship between left ventricular apical thrombus and myocardial viability has not been previously described. Eighty patients with coronary artery disease and chronic left ventricular dysfunction were studied by dobutamine stress echocardiography. Left ventricular apical thrombus was identified using echocardiographic criteria. Wall-motion analysis was performed using a standard 16-segment model and ejection fraction was calculated. As a result, 48 patients (60%) had definite or highly suspicious findings for left ventricular thrombus (group 1), and 32 patients (40%) had no thrombus (group 2). Group 1 had significantly higher composite (54.0 +/- 5.8 vs 43.3 +/- 6.4) and apical (6.0 +/- 2.7 vs 12.4 +/- 3.4) wall-motion scores compared to those in group 2 (P = 0.01). Thirty-two patients (67%) in group 1 demonstrated no contractile reserve in the apical segments, consistent with lack of viability, versus eight patients (25%) in group 2 (P = 0.0003). The number of viable apical segments per patient was significantly less in group 1 (0.7 +/- 1.2) versus group 2 (1.8 +/- 1.3) (P = 0.01). Left ventricular apical thrombus is more likely to be present when there is absence of myocardial viability in the corresponding segments.

Adult↗
PubMed2000

Enhanced detection of ischemic myocardium by transesophageal dobutamine stress echocardiography: comparison with simultaneous transthoracic echocardiography.

The diagnostic accuracy of dobutamine stress echocardiography is limited in patients with poor transthoracic acoustic windows. Transesophageal echocardiography (TEE) overcomes these limitations and thus may increase the clinical usefulness of dobutamine stress echocardiography. The present study was designed to compare the diagnostic accuracies of transesophageal and transthoracic dobutamine stress echocardiography for the identification of coronary artery disease (CAD) in a cohort of patients with a higher incidence of poor acoustic windows. Forty-two male patients (mean age, 66 +/- 9 years) underwent dobutamine stress echocardiography with simultaneous transesophageal and transthoracic imaging. Coronary arteriography was performed in 28 patients (67%). Transesophageal imaging adequately visualized 99.6% of left ventricular segments compared with 76.2% visualized by transthoracic imaging (P < 0.0001). There was substantial agreement between the two techniques for segmental wall motion analysis at baseline (kappa 0.76; 95% CI, 0.70-0.82); however, at peak dobutamine dose, agreement was significantly reduced (kappa 0.62; 95% CI, 0.55-0.69). The sensitivity (88% vs 75%), specificity (100% vs 75%), and positive predictive value (100% vs 80%) for the identification of CAD were all superior for transesophageal imaging. Transesophageal imaging correctly identified 11 of the 12 patients (92%) with multivessel disease compared with 5 patients (42%) identified by transthoracic imaging (P < 0.03). There were no major complications. Transesophageal dobutamine stress echocardiography is a safe, feasible, and accurate technique for the identification and risk stratification of patients with CAD. Transesophageal imaging appears to be superior to transthoracic imaging for identifying both the presence and extent of CAD, specifically in patients with poor acoustic windows.

Aged↗