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Biomedical subjects

R O Bonow

Publications and source records attributed to R O Bonow.

At least 73 records · Page 4Linked to original sources

Alterations in ultrasonic backscatter during exercise-induced myocardial ischemia in humans.

BACKGROUND: Experimentally induced myocardial ischemia in animals causes tissue modifications that alter characteristics of the ultrasonic beam backscattered from the myocardial muscle. Alterations of backscatter parameters have been evidenced in human subjects with acute or remote myocardial infarction and during ischemia induced by angioplasty balloon occlusion or pharmacological stimuli. The effects of transient effort ischemia in humans have not been reported. The purpose of this study is to assess ultrasonic backscatter parameter changes induced by transient effort myocardial ischemia in human subjects. METHODS AND RESULTS: Nineteen patients with single left anterior descending coronary stenosis and 15 healthy subjects underwent ultrasonic backscatter analysis (parasternal long-axis view) at rest, immediately after a supine stress test, and 30 minutes later. Two windows were selected in each ultrasonic study: one encompassing the septum; the other, the posterior wall. Integrated backscatter was computed throughout the cardiac cycle, yielding a power curve relative to the midmyocardial region of the myocardial wall (excluding pericardial and endocardial borders). Five parameters were computed from the backscatter power curve: the maximum-minimum difference, amplitude and phase of the first harmonic Fourier fitting, phase-weighted amplitude, and time-averaged integrated backscatter difference from rest (an index of overall myocardial reflectivity). This protocol allowed comparison of the backscatter data from a region at risk of ischemia (the septum) with that from a region normally perfused (posterior wall) and a comparison with the same regions of the control group during the three ultrasonic studies. All backscatter indexes in the septum were altered significantly by exercise compared with rest values, whereas no changes were found in the normally perfused posterior wall or in the septum of the control group. All modified parameters returned to baseline values at the time of the recovery study. CONCLUSIONS: These data indicate that transient, exercise-induced ischemia is associated with reduction of the cardiac cycle-dependent variation of the integrated backscatter power curve, a temporal shift in the nadir of the power curve with respect to the R wave (phase increase), and a small but detectable increase of myocardial reflectivity. These changes may be detected noninvasively in humans with ultrasonic backscatter analysis.

Adult↗

The hibernating myocardium: implications for management of congestive heart failure.

Left ventricular (LV) function is one of the most important determinants of long-term outcome in patients with coronary artery disease (CAD). Patients with normal or near-normal LV function have an excellent prognosis, whereas patients with impaired LV function are at substantial risk of death during medical therapy. It is now apparent that LV dysfunction is not always an irreversible process and that LV function may improve considerably, and even normalize, after myocardial revascularization in a large subset of patients. The identification of such patients with "hibernating" myocardium that is underperfused and dysfunctional, yet viable, has important implications in the selection of patients with LV dysfunction for revascularization procedures. Both nuclear cardiology techniques and 2-D echocardiography can be used for this purpose. The radionuclide techniques include positron emission tomography to assess blood flow and metabolism (using agents such as [18F]fluorodeoxyglucose) and thallium-201 (and possibly technetium-99m sestamibi) to assess blood flow and cell membrane integrity. Alternatively, echocardiographic imaging during low-dose infusions of dobutamine can be used to assess inotropic reserve. The data available to date suggest that patients with CAD in whom hibernating myocardium is largely the cause of impaired LV function constitute a subgroup of patients who may achieve a substantial improvement in LV function and in outcome if identified and treated with revascularization.

Echocardiography↗

Functional evaluation of patients with coronary artery disease: selection of appropriate pharmacologic agents and imaging modalities.

Exercise myocardial perfusion imaging and exercise echocardiography have been applied widely for diagnosis and risk stratification of patients with known or suspected coronary artery disease. The accuracy of these evaluations depends upon the ability of the patient to achieve maximal exercise (> 85% of age-predicted maximal heart rate). In patients unable to exercise or with a limited capacity to exercise maximally, pharmacologic stress imaging is a safe and effective alternative to exercise stress imaging. Pharmacologic stress is also indicated in patients with resting or exercise-induced left bundle branch block. Vasodilator stress with dipyridamole or adenosine, as well as catecholamine stimulation with dobutamine or preliminarily with arbutamine, provides diagnostic and prognostic information that appears to be equivalent to that achieved with exercise imaging. In addition, low dose catecholamine infusion during echocardiography to assess inotropic reserve is valuable in identifying viable myocardium in patients with left ventricular dysfunction and appears to assess viability with an accuracy that approaches that of nuclear cardiology methods. Hence, pharmacologic stress imaging, like exercise stress imaging, has important implications regarding patient outcome, patient management, and selection of patients for interventional therapy.

Coronary Disease↗

Valve replacement for regurgitant lesions of the aortic or mitral valve in advanced left ventricular dysfunction.

Patients with aortic regurgitation and severe left ventricular dysfunction remain candidates for aortic valve replacement, as long as the risks of late left ventricular dysfunction and congestive heart failure have been fully discussed with the patient, the patient's family, and the referring physician. In contrast, patients with mitral regurgitation and severe systolic dysfunction are at considerable risk of more severe left ventricular dysfunction after operation, especially if mitral valve repair or chordal-sparing procedure cannot be performed. In patients who are candidates for such procedures that preserve the integrity of the subvalvular mitral apparatus, operation may be successful in selected patients despite moderate-to-severe depression of systolic function. Prognosis is guarded to poor in patients with regurgitant valvular lesions and advanced left ventricular dysfunction, and the emerging alternative treatments discussed in other articles in this Cardiology Clinics deserve consideration in these patients.

Aortic Valve↗

Clinical significance of reduced regional myocardial glucose uptake in regions with normal blood flow in patients with chronic coronary artery disease.

OBJECTIVES: The objective of this study was to assess the clinical significance of reduced regional fluorine-18 (18F) fluorodeoxyglucose uptake with normal flow in patients with chronic coronary artery disease. BACKGROUND: In patients with ischemic left ventricular dysfunction, 18F-fluorodeoxyglucose uptake may be reduced in some myocardial regions despite normal flow. The significance of this finding is unclear and has not been investigated systematically. METHODS: Twenty-three patients with coronary artery disease and impaired ventricular function (mean ejection fraction [+/- 1 SD] 28 +/- 10%) underwent positron emission tomography with 18F-fluorodeoxyglucose and oxygen-15-labeled water at rest, exercise thallium-201 tomographic imaging with rest reinjection and gated magnetic resonance imaging to measure end-diastolic wall thickness and systolic wall thickening. RESULTS: Of 168 regions with normal flow (> or = 0.7 ml/g per min), 125 (74%) had normal 18F-fluorodeoxyglucose uptake (98 +/- 10%), and the remaining 43 (26%) showed moderately reduced 18F-fluorodeoxyglucose uptake (69 +/- 8%). Systolic wall thickening was absent at rest in 14% of regions with normal 18F-fluorodeoxyglucose uptake compared with 32% of regions with reduced 18F-fluorodeoxyglucose uptake (p < 0.01). Reversible thallium abnormalities were observed in 45 (36%) of 125 regions with normal 18F-fluorodeoxyglucose uptake compared with 27 (63%) of 43 regions with reduced 18F-fluorodeoxyglucose uptake (p < 0.01). This difference was accounted for by a higher proportion of partially reversible defects in regions with reduced 18F-fluorodeoxyglucose uptake compared with regions with normal 18F-fluorodeoxyglucose uptake (42% vs. 18%, respectively, p < 0.01). CONCLUSIONS: Thus, regions with moderately reduced 18F-fluorodeoxyglucose uptake with normal flow occur commonly in patients with ischemic left ventricular dysfunction. The majority of these regions show impaired systolic function at rest and exercise-induced thallium abnormalities that are only partially reversible. These observations suggest that such regions represent an admixture of fibrotic and reversibly ischemic myocardium.

Coronary Circulation↗

Asymptomatic aortic regurgitation: indications for operation.

Left ventricular (LV) systolic function is an important determinant of long-term prognosis in patients with chronic aortic regurgitation. In patients undergoing aortic valve replacement (AVR), those with preoperative LV dysfunction have a greater risk of postoperative congestive heart failure and death than do those in whom preoperative LV systolic function is normal. Patients with preoperative LV dysfunction are not a homogeneous group, however, but may be further stratified according to risk on the basis of the severity of symptoms, exercise intolerance, and temporal duration of LV dysfunction. Hence, asymptomatic patients with reproducible and definite evidence of impaired LV function should undergo operation without waiting for the development of symptoms or more severe LV dysfunction. Among asymptomatic patients with normal LV systolic function (normal ejection fraction and fractional shortening), the prognosis is excellent with only a gradual rate of deterioration during conservative, nonoperative management. The long-term follow-up experience of such patients indicates that the annual mortality rate is less than 0.5% and that less than 4% per year require AVR because symptoms or LV dysfunction at rest develop. Patients likely to require operation over a 10-year period because symptoms or LV dysfunction develop can be identified on the basis of age, severity of LV dilatation by echocardiography, and progressive change in LV dimensions or resting ejection fraction during the course of serial follow-up studies. Patients at risk of sudden death before surgery is performed may be identified by extreme LV dilatation (diastolic dimension > 80 mm, systolic dimension > 55 mm).(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve Insufficiency↗

Myocardial viability in patients with chronic coronary artery disease. Comparison of 99mTc-sestamibi with thallium reinjection and [18F]fluorodeoxyglucose.

BACKGROUND: 99mTc-sestamibi and thallium imaging have similar accuracy when used for diagnostic purposes, but whether sestamibi provides accurate information regarding myocardial viability in patients with chronic coronary artery disease has not been established. Since there is minimal redistribution of sestamibi over time, it may overestimate nonviable myocardium in patients with left ventricular dysfunction, in whom blood flow may be reduced at rest. METHODS AND RESULTS: We studied 54 patients with chronic coronary artery disease with a mean ejection fraction of 34 +/- 14%. Patients underwent stress/redistribution/reinjection thallium tomography and, within a mean of 5 days, same-day rest/stress sestamibi imaging using the same exercise protocol and with patients achieving the same exercise duration. Of the 111 reversible thallium defects on either the redistribution or reinjection study, 40 (36%) were determined to be irreversible on the rest/stress sestamibi study, whereas only 3 of 63 irreversible thallium defects despite reinjection (5%) were classified to be reversible by sestamibi imaging. The concordance regarding reversibility of myocardial defects between thallium stress/redistribution/reinjection and same day rest/stress sestamibi studies was 75%. A subgroup of 25 patients also underwent positron emission tomography (PET) studies with 15O-labeled water and [18F]fluorodeoxyglucose (FDG) at rest after an oral glucose load. As in the overall group of 54 patients, there was concordance between thallium and sestamibi imaging regarding defect reversibility in 51 of 73 regions (70%). In the remaining 22 discordant regions (30%), 18 (82%) appeared irreversible by sestamibi imaging but were reversible by thallium imaging. Myocardial viability was confirmed in 17 of 18 regions, as evidenced by normal FDG uptake (10 regions) or FDG/blood flow mismatch (7 regions) on PET. These regions were present in 16 of the 25 patients studied (64%). We then explored methods to improve the sestamibi results. First, when the 18 discordant regions with irreversible sestamibi defects were further analyzed according to the severity of defects, 14 (78%) demonstrated only mild-to-moderate reduction in sestamibi activity (51% to 85% of normal activity), suggestive of predominantly viable myocardium, and the overall concordance between thallium and sestamibi studies increased to 93%. Second, when an additional 4-hour redistribution image was acquired in 18 patients after the injection of sestamibi at rest, 6 of 16 discordant irreversible regions (38%) on the rest/stress sestamibi study became reversible, thereby increasing the concordance between thallium and sestamibi studies to 82%. CONCLUSIONS: These data indicate that same-day rest/stress sestamibi imaging will incorrectly identify 36% of myocardial regions as being irreversibly impaired and nonviable compared with both thallium redistribution/reinjection and PET. However, the identification of reversible and viable myocardium can be greatly enhanced with sestamibi if an additional redistribution image is acquired after the rest sestamibi injection or if the severity of reduction in sestamibi activity within irreversible defects is considered.

Adult↗

Improvement of the age-related impairment in left ventricular diastolic filling with verapamil in the normal human heart.

BACKGROUND: Left ventricular (LV) diastolic function declines with the normal aging process. Because these changes are related to impaired active LV relaxation as well as to structural alterations, we hypothesized that verapamil might improve LV filling in elderly normal subjects compared with young normal subjects. METHODS AND RESULTS: We studied 27 normal volunteers (between 20 and 71 years old), with normal exercise tests and echocardiograms, by radionuclide angiography before and after 3 to 4 days of oral verapamil therapy. Indexes of global LV function were derived from analysis of background-corrected time-activity curves. Subjects were recruited from three age groups: young (26 +/- 4 years, n = 10), middle-aged (46 +/- 5 years, n = 9), and elderly (66 +/- 3 years, n = 8). Baseline resting heart rate, blood pressure, peak systolic wall stress, and LV ejection fraction did not differ among groups. Baseline peak LV filling rate (expressed in fractional stroke volume per second) was reduced in the middle-aged group (5.8 +/- 1.2, P < .01) and the elderly group (4.3 +/- 1.0, P < .01) compared with the young group (7.8 +/- 1.2). With verapamil, resting heart rate, peak systolic wall stress, LV ejection fraction, and peak ejection rate did not change in any group. Peak filling rate increased in the middle-aged group (to 6.8 +/- 1.5 SV/s, P < .01) and the elderly group (to 5.7 +/- 1.0 SV/s, P < .01) but did not change in the young group (8.0 +/- 1.4 SV/s). Also, time to peak filling rate decreased with verapamil in the elderly group (from 185 +/- 31 to 147 +/- 15 milliseconds, P < .01). The magnitude of change in filling rate was correlated positively with age (r = .55, P < .005). CONCLUSION: Verapamil selectively enhances LV diastolic filling in middle-aged and elderly subjects, compared with young adults, without affecting systolic function. This observation supports the hypothesis that the impairment of LV filling accompanying the normal aging process is, at least in part, a reversible phenomenon.

Adult↗

Radionuclide angiography for risk stratification of patients with coronary artery disease.

Radionuclide angiography has become an accepted diagnostic method that is relied upon for its rapid, accurate and quantitative capabilities to characterize LV function. This method will continue to be used extensively in the future for the evaluation of patients with CAD. In addition to its common use to measure LV function at rest, the application of radionuclide angiography to assess LV function during exercise has proven prognostic potential that can be used in the clinical decision-making process in patients with known or suspected CAD.

Coronary Disease↗

Regional systolic function, myocardial blood flow and glucose uptake at rest in hypertrophic cardiomyopathy.

Decreased 18fluorodeoxyglucose (FDG) uptake and blood flow at rest in the ventricular septum, as compared with the lateral wall, have been reported in mildly symptomatic patients with hypertrophic cardiomyopathy (HC). To assess whether regional metabolic heterogeneity in patients with HC is related to heterogeneous regional systolic function, 10 symptomatic patients (mean age 36 +/- 17 years) with HC and no coronary artery disease underwent positron emission tomography with oxygen-15-water and FDG, and nuclear magnetic resonance imaging at rest to assess regional anatomy and systolic function. Regional absolute blood flow was similar between the ventricular septum and lateral wall. In contrast, FDG activity was significantly greater in the lateral wall than in the septum (1,023 +/- 588 vs 767 +/- 388 nCi/ml, respectively; p < 0.01). However, regional systolic wall thickening was also significantly greater in the lateral wall than in the septum (5.3 +/- 4.3 vs 2.4 +/- 4.0 mm, respectively; p < 0.001). Patients were then divided into group A (n = 5) with similar regional wall thickening in the septum and lateral wall, and group B (n = 5) with greater thickening in the lateral wall than in the septum. In both groups, regional blood flow was similar between the septum and lateral wall. However, the regional septal-to-lateral FDG activity ratio was 0.97 +/- 0.31 in group A, and 0.74 +/- 0.25 in group B (p < 0.01); the ratio in group A did not differ from that in 5 normal subjects (1.02 +/- 0.58).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Prognostic implications of myocardial ischemia during daily life in low risk patients with coronary artery disease.

OBJECTIVES: The purpose of this study was to determine the incidence and prognostic importance of myocardial ischemia detected by ambulatory monitoring in low risk, medically managed patients with coronary artery disease. BACKGROUND: Previous studies have demonstrated that certain high risk subsets of patients with coronary artery disease have improved survival with revascularization. The remaining low risk medically managed patients may still have episodes of silent ischemia during daily living, but the frequency and prognostic implications of such episodes in this group are unknown. METHODS: We prospectively studied the incidence and prognostic significance of ST segment changes recorded during daily activities in 116 asymptomatic or mildly symptomatic low risk patients with native coronary artery disease who were followed up for 29 +/- 13 months. Low risk patients were selected after excluding patients with 1) left main disease; 2) three-vessel coronary artery disease and left ventricular dysfunction at rest; 3) three-vessel disease and inducible ischemia during exercise; and 4) two-vessel disease, left ventricular dysfunction and inducible ischemia. RESULTS: Forty-five patients (39%) had transient episodes of ST segment depression during 48-h electrocardiographic (ECG) monitoring (total 217 episodes, lasting 7,223 min, 82% of episodes silent). There were eight acute cardiac events (seven myocardial infarctions, one episode of unstable angina) and nine patients underwent elective revascularization. Seven of the eight acute events occurred in patients without silent ischemia during monitoring. Kaplan-Meier survival analysis revealed no significant differences in event-free survival from either acute or total events in subgroups with or without silent ischemia during ambulatory ECG monitoring. None of the clinical, treadmill exercise, radionuclide ventriculographic or cardiac catheterization variables were predictive of outcome by Cox multivariate proportional hazard function analysis. Analysis of coronary arteriograms before and after acute cardiac events revealed that in five of the six patients studied, acute occlusion occurred in a coronary artery different from the artery with the severest stenosis on initial angiography. CONCLUSIONS: In patients categorized as at low risk on the basis of the results of cardiac catheterization and stress testing, silent myocardial ischemia during daily life was not uncommon, and its presence failed to predict future coronary events.

Activities of Daily Living↗

Angiogenic effects of low molecular weight heparin in patients with stable coronary artery disease: a pilot study.

OBJECTIVES: The study was designed to assess the feasibility of conducting a trial to investigate whether exercise and low molecular weight heparin therapy with dalteparin sodium (Fragmin) would improve collateral function to the ischemic myocardium in patients with coronary artery disease. BACKGROUND: The severity of myocardial ischemia in patients with coronary artery disease is at least partly dependent on the status of the collateral circulation. Therefore, improvement in collateral function would potentially provide a unique way of alleviating myocardial ischemia. Because the combination of ischemia and heparin has previously been demonstrated to enhance collateral growth, we studied the anti-ischemic effects of combined treatment with dalteparin sodium and exercise-induced ischemia in patients with coronary artery disease. METHODS: Twenty-three patients with stable coronary artery disease were randomized to receive either subcutaneous dalteparin sodium or placebo for a 4-week period. Patients received either placebo or 10,000 IU of dalteparin sodium by subcutaneous injection once daily for weeks 1 and 2 and 5,000 IU daily for weeks 3 and 4. During the 1st 2 weeks, patients were exercised to ischemia three times a day. At baseline and 4 weeks after treatment, treadmill exercise testing, exercise radionuclide ventriculography and 48-h ambulatory ST segment monitoring were performed. RESULTS: Eight (80%) of the 10 dalteparin sodium-treated patients compared with 4 (31%) of 13 placebo-treated patients (p < 0.02) had an increased rate-pressure product at the onset of 1 mm of ST segment depression. The duration of exercise to ischemia increased in all patients treated with low molecular weight heparin and in 62% of placebo-treated patients (p < 0.03). The number and duration of episodes of ST segment depression during ambulatory monitoring decreased by 30% and 35%, respectively (p < 0.05), in the dalteparin sodium group but were unchanged in the placebo group. The decrease in left ventricular ejection fraction with exercise was lower in 80% of dalteparin sodium-treated patients compared with 54% of placebo-treated patients (p = 0.06). When all five factors reflecting collateral function were considered together in a multivariate analysis of variance, there was a significant improvement in low molecular weight heparin-treated patients compared with placebo-treated patients (p = 0.014). CONCLUSIONS: This study provides preliminary evidence suggesting that exercise and low molecular weight heparin therapy with dalteparin sodium lessen myocardial ischemia and that the improvement is likely to be mediated by enhanced collateral function.

Aged↗