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Biomedical subjects

R O Bonow

Publications and source records attributed to R O Bonow.

At least 127 records · Page 7Linked to original sources

[Identification of viable myocardium in patients with chronic ischemic disease and left ventricular dysfunction: correlations between blood flow, metabolic activity and regional function].

To identify the presence of viable myocardium in areas of severe systolic dysfunction, we studied 22 patients (age 45 to 78 years) with chronic coronary artery disease and left ventricular dysfunction (mean ejection fraction 29 +/- 9%). All subjects underwent thallium-201 single photon emission computed tomography (SPECT), using the reinjection technique, positron emission tomography (PET) with H2(15)O and 18-fluorodeoxyglucose (FDG) to measure regional blood flow and exogenous glucose uptake, respectively, and nuclear magnetic resonance imaging (MRI). From matched transaxial PET, SPECT and MRI tomograms, a total of 290 left ventricular myocardial regions were analyzed. According to the regional wall thickening, measured from MRI, 3 groups of myocardial regions were identified: akinetic-dyskinetic (n = 60), showing either absence of systolic thickening or systolic thinning; hypokinetic (n = 97), showing an absolute wall thickening less than or equal to 2 mm; normal (n = 133), showing an absolute wall thickening greater than 2 mm. Of the 60 akinetic or dyskinetic regions, 3 were normal by SPECT and 37 corresponded to either a total or partially reversible thallium defect: 34 of these 40 regions also showed presence of FDG uptake by PET. The remaining 20 akinetic or dyskinetic regions showed a thallium defect that remained irreversible after reinjection: in 7 of these 20 regions, however, there was evidence of metabolic activity, as expressed by FDG uptake. Thus, 47 (78%) of the myocardial akinetic or dyskinetic regions showed presence of viable tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Exercise testing in patients with microvascular angina.

The widespread use of exercise testing for the detection of myocardial ischemia in patients suspected of having coronary artery disease led to the detection of ischemic changes in many subjects who subsequently were found to have angiographically normal epicardial vessels--the false positive response. Such a result is usually interpreted as indicating that the subject's chest pain is of noncardiac origin. For the past several years, we have studied the mechanism of pain resembling angina that occurs in patients with normal epicardial coronary arteries demonstrated by angiography; we believe these studies have shed some light on this problem. Patients with angiographically normal coronary arteries who present because of a history of angina-like pain and/or ischemic changes detected during exercise electrocardiogram testing were evaluated by measuring great cardiac vein flow (under baseline conditions and after cardiac pacing, with and without intravenous administration of ergonovine) and by radionuclide angiography before and during exercise. We found that a substantial number of these subjects showed inadequate coronary vasodilator reserve and had exercise-induced left ventricular dysfunction suggestive of myocardial ischemia. We concluded from our results that there is a distinct clinical syndrome of myocardial ischemia caused by abnormal resistance responses of the prearteriolar coronary microvasculature. We now refer to this syndrome as microvascular angina. In a series of 115 patients with documented microvascular angina, we also found that only 10% had ischemic ST changes with exercise testing (2% of the men and 17% of the women developed ischemic ST segment changes).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Comparison of exercise testing with studies of coronary flow reserve in patients with microvascular angina.

Abnormal small coronary artery function may cause limited coronary flow responses to stress, resulting in anginal symptoms and ischemia in some patients with chest pain despite angiographically normal coronary arteries. To assess the exercise hemodynamic correlates of coronary flow abnormalities measured in the cardiac catheterization laboratory, 105 patients with microvascular angina (defined as an increase in coronary vascular resistance during pacing stress after ergonovine administration in the absence of significant epicardial constriction and associated with provocation of the patient's typical chest pain) and 27 patients without any coronary flow abnormality (normal) were analyzed. Of the 105 patients with microvascular angina, 75 had normal electrocardiographic responses to treadmill exercise testing, 22 had ischemic responses, and eight had bundle branch block during exercise. All 27 normal patients had normal electrocardiographic responses to exercise. Patients with ischemic electrocardiographic responses (0 +/- 7%, p less than 0.01), and those with bundle branch block (-2 +/- 6%, p less than 0.01) had abnormal left ventricular ejection fraction responses to exercise compared with the normal group, who demonstrated an 8 +/- 6% increase in left ventricular ejection fraction by radionuclide angiography during exercise, and microvascular angina patients with a normal electrocardiographic response to exercise, who demonstrated a 5 +/- 7% increase in ejection fraction. Although the microvascular response to ergonovine was no different among the three microvascular angina exercise groups, the administration of dipyridamole caused less coronary vasodilation in those patients with apparently ischemic or bundle branch block responses to exercise compared with those with normal electrocardiograms during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris↗

Left ventricular diastolic function in hypertrophic cardiomyopathy.

Impaired diastolic function of the hypertrophied and stiffened left ventricle is a characteristic feature of hypertrophic cardiomyopathy (Figure 1). Altered left ventricular filling dynamics and reduced left ventricular distensibility or increased left ventricular diastolic chamber stiffness are associated with reduced left ventricular stroke volume, increased left ventricular filling pressures and compressive effects on the coronary microcirculation. These factors contribute importantly to the clinical presentation of many patients, including symptoms of fatigue, dyspnea and angina pectoris. Reduced distensibility results both from factors determining the passive elastic properties of the ventricular chamber (including severity of hypertrophy, fibrosis and cellular disarray) and from factors influencing the rate and extent of active left ventricular relaxation (Figure 2). The factors contributing to impaired relaxation in hypertrophic cardiomyopathy are mediated via either inactivation dependent or load-dependent mechanisms. In laboratory animals, compromise of myocardial inactivation results in a persistent increase in intracellular calcium concentration and in prolonged interaction of the contractile proteins. Additionally, there is evidence for an increased number of active receptors for calcium antagonists and, lastly, for myocardial ischemia (Figure 3). Load-dependent mechanisms include diminished wall tension at the opening of the mitral valve, changes in afterload, contractility and coronary flow. Other factors are nonuniform and asynchronous regional ventricular function due to differing increases in thickness of the ventricular walls and ischemia (Figure 4). Calcium channel blockers exert a favorable influence on left ventricular relaxation and filling (Figure 5); verapamil and diltiazem are preferable to nifedipine. Verapamil increases left ventricular stroke volume without an increase in the end-diastolic pressure (Figure 6), reduces regional asynchrony if present, and leads to a more homogeneous regional diastolic filling (Figure 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomyopathy, Hypertrophic↗

Enhanced detection of ischemic but viable myocardium by the reinjection of thallium after stress-redistribution imaging.

BACKGROUND: The identification of ischemic but viable myocardium by thallium exercise scintigraphy is often imprecise, since many of the perfusion defects that develop in ischemic myocardium during exercise do not "fill in" on subsequent redistribution images. We hypothesized that a second injection of thallium given after the redistribution images were taken might improve the detection of ischemic but viable myocardium. METHODS: We studied 100 patients with coronary artery disease, using thallium exercise tomographic imaging and radionuclide angiography. Patients received 2 mCi of thallium intravenously during exercise, redistribution imaging was performed three to four hours later, and a second dose of 1 mCi of thallium was injected at rest immediately thereafter. The three sets of images (stress, redistribution, and reinjection) were then analyzed. RESULTS: Ninety-two of the 100 patients had exercise-induced perfusion defects. Of the 260 abnormal myocardial regions identified by stress imaging, 85 (33 percent) appeared to be irreversible on redistribution imaging three to four hours later. However, 42 of these apparently irreversible defects (49 percent) demonstrated improved or normal thallium uptake after the second injection of thallium, with an increase in mean regional uptake from 56 +/- 12 percent on redistribution studies to 64 +/- 10 percent on reinjection imaging (P less than 0.001). Twenty patients were restudied three to six months after coronary angioplasty. Of the 15 myocardial regions with defects on redistribution studies that were identified as viable by reinjection studies before angioplasty, 13 (87 percent) had normal thallium uptake and improved regional wall motion after angioplasty. In contrast, all eight regions with persistent defects on reinjection imaging before angioplasty had abnormal thallium uptake and abnormal regional wall motion after angioplasty. CONCLUSIONS: These data indicate that the reinjection of thallium improves the detection of ischemic myocardium and that myocardial regions with improved thallium uptake on reinjection imaging represent viable but jeopardized myocardium.

Adult↗

Left ventricular hypertrophy and impaired diastolic filling in essential hypertension. Diastolic mechanisms for systolic dysfunction during exercise.

Left ventricular ejection fraction is normal at rest but may respond abnormally to exercise in many patients with essential hypertension. To assess the determinants of the abnormal ejection fraction response to exercise, we performed radionuclide angiography at rest and during exercise in 41 hypertensive patients without coronary artery disease. In 22 patients (group 1), the ejection fraction increased more than 5% during exercise; in the other 19 patients (group 2), the ejection fraction either increased by less than 5% or decreased with exercise. Left ventricular diastolic filling was impaired at rest in patients in group 2 compared with group 1, with reduced peak filling rate (2.5 +/- 0.4 vs. 3.1 +/- 0.7 end-diastolic volume/sec; p less than 0.01) and prolonged time to peak filling rate (175 +/- 28 vs. 153 +/- 22 msec; p less than 0.01). Impaired diastolic filling in group 2 was associated with less augmentation in end-diastolic volume during exercise compared with group 1 (p less than 0.01). These observations were not dependent on the threshold value that was arbitrarily chosen to define an abnormal ejection fraction response, as there were significant correlations for the entire group between the magnitude of change in ejection fraction with exercise and both the resting peak filling rate (r = 0.46) and the change in end-diastolic volume with exercise (r = 0.62).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomegaly↗

Minimum left ventricular pressure during beta-adrenergic stimulation in human subjects. Evidence for elastic recoil and diastolic "suction" in the normal heart.

The influence of elastic recoil and restoring forces on diastolic left ventricular pressure decay and minimum left ventricular pressures has been demonstrated in animal models but has not been studied in the human heart. To investigate this issue in the normal human left ventricle, we studied eight patients with chest pain and normal coronary arteries with simultaneous measurement of left ventricular volume (by radionuclide angiography) and pressure (by micromanometer catheter) and coronary sinus blood flow. Electrocardiographic-gated data were obtained in the basal state, during rapid atrial pacing, and during isoproterenol infusion to a similar heart rate. Compared with pacing, isoproterenol increased ejection fraction and reduced end-systolic volume (p less than 0.005), end-systolic pressure (p less than 0.005), and the half-time of pressure decline after peak negative dP/dt (T1/2) (p less than 0.001). Negative diastolic pressure developed in seven of eight patients during isoproterenol (range, -0.5 to -2.4 mm Hg) but in only one of eight during pacing (-0.2 mm Hg). These reduced diastolic pressures during isoproterenol were accompanied by increased stroke volume (reflecting increased transmitral flow) and diminished pulmonary wedge pressure (reflecting left atrial pressure). The magnitude of reduction in minimum diastolic pressure during pacing and isoproterenol was related to the change in end-systolic volume (r = 0.79, p less than 0.001), ejection fraction (r = -0.74, p less than 0.001), T1/2 (r = -0.57, p less than 0.02), and coronary sinus flow (r = 0.73, p less than 0.005). Stronger correlations were observed in analyzing changes during isoproterenol alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗

Comparison of fixed and variable temporal resolution methods for creating gated cardiac blood-pool image sequences.

In each of 50 resting subjects, two gated blood-pool image sequences were created from the same LIST mode data set. One sequence was created using a sorting method that spans each individual cardiac cycle with the same number of images (the "variable temporal" or VT method), while the other (the "fixed temporal" or FT method) spans the average cardiac cycle with images of fixed temporal duration. Left ventricular time-activity curves were extracted from each sequence using identical regions-of-interest and analyzed with identical methods to obtain estimates of ejection fraction, peak ejection rate, peak filling rate, and the times of occurrence of these peak rates. Differences among certain of these parameters in kind and amount support the hypothesis that estimates of resting cardiac function are more accurately portrayed by the FT method. The magnitudes of these differences are small for systolic parameters but large for early diastolic parameters. Thus, although both methods might be used for measuring systolic function, the FT method will yield a more accurate estimate of peak filling rate in resting subjects.

Gated Blood-Pool Imaging↗

Comparative assessment of chordal preservation versus chordal resection during mitral valve replacement.

Left ventricular function often deteriorates after mitral valve replacement for mitral regurgitation. It has been postulated that disruption of the mitral valve apparatus at operation is a major mechanism of postoperative dysfunction. The hypothesis tested in this investigation was that chordal preservation results in more favorable left ventricular function. Sixty-nine patients with isolated mitral regurgitation who underwent mitral valve replacement were studied before and 6 months after operation by treadmill exercise testing, catheterization, echocardiography, and radionuclide angiography. Nine patients underwent mitral valve replacement with preservation of the entire mitral apparatus and five with preservation of the posterior leaflet and attached chordae. The remaining 55 had mitral valve replacement with complete excision of the native valve. Preoperatively, there were no differences among groups in age, gender, exercise capacity, cardiac index, rest or exercise ejection fraction, fractional shortening, or pulmonary artery pressures. There were four perioperative deaths (7%) and eight late deaths among the 55 patients with chordal resection but no early or late deaths of patients whose chordae were preserved (p = 0.05). In patients in whom the chordae were excised, exercise capacity, left ventricular systolic dimensions, and cardiac index did not improve after mitral valve replacement, and left ventricular function deteriorated, as evidenced by a reduction of both the resting and exercise ejection fractions (from 46% +/- 13% to 31% +/- 13%, p = 0.0001, and from 49% +/- 12% to 37% +/- 14%, p = 0.0007, respectively) and fractional shortening (from 34% +/- 10% to 26% +/- 14%, p = 0.0001). In contrast, exercise capacity improved after mitral valve replacement in patients in whom the entire apparatus was spared (by 4 +/- 3 minutes, p = 0.05), left ventricular systolic dimensions decreased (from 44 +/- 8 to 36 +/- 9 mm, p = 0.03), and left ventricular function was maintained or improved, as evidenced by preservation of the resting ejection fraction (preoperative, 50% +/- 14%; postoperative, 54% +/- 11%; p = no significant difference), exercise ejection fraction (46% +/- 16% versus 52% +/- 9%, p = no significant difference), fractional shortening (from 31% +/- 9% to 28% +/- 9%, p = no significant difference), and an increase in the cardiac index (from 2.0 +/- 0.3 to 2.7 +/- 0.5 L/min/m2, p = 0.05). No statistically significant differences between posterior chordal resection only and preservation of the entire apparatus were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of temporal smoothing on quantitation of left ventricular function by gated blood pool scintigraphy.

Frequently, indexes of systolic and diastolic left ventricular (LV) function obtained from radionuclide angiography are computed after the LV time-activity curve has been temporally smoothed. This smoothing process may introduce important systematic errors into the analysis. To assess this potential effect, high temporal resolution time-activity curves (20 ms/point) were obtained in 113 normal subjects, 175 patients with coronary artery disease and 171 patients with hypertrophic cardiomyopathy. The curves were then subjected to 0-, 3-, 5-, 7- and 9-point temporal smoothing. In each group, increased smoothing progressively and consistently underestimated ejection fraction by up to 5% (p less than 0.001) and peak ejection rate by up to 14% (p less than 0.001). A greater effect on peak filling rate was observed: 5-point and 9-point smoothing reduced peak filling rate by 10% and 23% in normal subjects, 3% and 10% in patients with coronary artery disease and 7% and 15%, respectively, in patients with hypertrophic cardiomyopathy (all p less than 0.001). These errors were compounded further when the same data obtained at lower temporal resolution (40 ms/point) were analyzed: 5-point and 9-point smoothing resulted in underestimation of peak filling rate by 20% and 46% in normal subjects, 13% and 43% in coronary artery disease and 16% and 34% in hypertrophic cardiomyopathy. The underestimation was not uniform, and its magnitude varied considerably among individuals in each of the 3 groups. Thus, smoothing of LV time-activity curves may result in significant systematic errors in computation of indexes of LV systolic and diastolic function, especially in data with poor temporal resolution. These concepts apply to other imaging methods, such as magnetic resonance imaging and cine-computed tomography, that assess LV function from the LV volume curve. Although ejection fraction is affected only mildly by these errors, both peak filling rate and peak ejection rate may be severely underestimated.

Algorithms↗

Relation between exertional ischemia and prognosis in mildly symptomatic patients with single or double vessel coronary artery disease and left ventricular dysfunction at rest.

The randomized multicenter trials indicate that survival in patients with coronary artery disease and left ventricular dysfunction is enhanced by surgical therapy compared with medical therapy. This beneficial effect of coronary bypass surgery was demonstrated in patients with either three vessel or left main coronary artery disease, but not in those with one or two vessel disease. To determine whether subgroups of mildly symptomatic patients with one or two vessel coronary artery disease and left ventricular dysfunction have an increased risk of death or cardiac events during medical therapy, 53 consecutive patients with angiographically defined one or two vessel disease and impaired left ventricular function (ejection fraction 20% to 40%) were studied by exercise electrocardiography (ECG) and rest and exercise radionuclide angiography. All but two patients had previous myocardial infarction, and all were asymptomatic or only mildly symptomatic during medical therapy. By univariate life table analysis, mortality during medical therapy was associated significantly with the ST segment response to exercise (p less than 0.05) and with both the exercise ejection fraction (p less than 0.05) and the magnitude of change in ejection fraction with exercise (p less than 0.005). In patients with an exercise ejection fraction greater than 30%, the probability of survival at 6 years was 97 +/- 3% (+/- SE) compared with a survival rate of 62 +/- 14% in the remaining subjects (p less than 0.005). Similarly, 6 year survival was 100% in patients whose ejection fraction increased from the value at rest but was only 74 +/- 10% in the remaining patients (p less than 0.005). Exercise capacity was not associated with survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Enhanced regional left ventricular function after distant coronary bypass by means of improved collateral blood flow.

To determine whether coronary artery bypass surgery can improve function in left ventricular regions not amenable to direct revascularization, 24 patients with multivessel coronary artery disease were studied by radionuclide angiography and coronary arteriography before and 6 months after coronary artery bypass surgery. All had proximal stenosis of the left circumflex artery or a major obtuse marginal branch. Left ventricular regional function was assessed by dividing the left ventricular region of interest into 20 sectors; the 8 sectors corresponding to the posterolateral free wall were used to assess function in the left circumflex artery distribution. Change in function in the left anterior descending territory was not analyzed because of the non-specific septal hypokinesia that develops postoperatively. For the total group, coronary artery bypass surgery significantly increased both global left ventricular ejection fraction during exercise (43 +/- 13% to 50 +/- 14%, p less than 0.001) and the change in ejection fraction from rest to exercise (-7 +/- 10% to 0 +/- 6%, p less than 0.001). Such improvement was observed in 9 of 10 patients with all stenoses bypassed, and to an equivalent degree in 9 of 10 patients in whom the left circumflex artery either could not be bypassed or the bypass graft was occluded (but bypass grafts to other coronary arteries were patent). Similarly, regional ejection fraction in posterolateral segments during exercise also increased comparably after operation in patients with a patent (from 57 +/- 18% to 70 +/- 19%, p less than 0.001) or nonpatent (from 51 +/- 14% to 68 +/- 14%, p less than 0.001) left circumflex graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Comparative effects of verapamil and nitroprusside on left ventricular function in patients with hypertension.

The effects of verapamil were compared with those of nitroprusside at matched mean arterial pressures and heart rates in 10 symptomatic hypertensive patients during cardiac catheterization. Simultaneous radionuclide angiography and micromanometer pressure measurements were obtained to assess left ventricular pressure-volume relations. Compared with control conditions, verapamil increased left ventricular end-diastolic volume index from 57 +/- 16 to 70 +/- 28 ml/m2 (p = 0.05) without a significant increase in left ventricular end-diastolic pressure (from 10 +/- 4 to 13 +/- 6 mm Hg). Despite a downward and rightward shift in the end-systolic pressure-volume relation indicating negative inotropic effects, ejection fraction did not decrease significantly (from 52 +/- 9% to 46 +/- 9%); cardiac index and stroke volume index remained unchanged. The change in stroke volume index with verapamil was directly related to the magnitude of change in end-diastolic volume index (r = 0.82, p less than 0.005), suggesting that the increase in end-diastolic volume did not arise purely from negative inotropic effects. Systemic vascular resistance index decreased from 42 +/- 8 to 34 +/- 7 mm Hg.min.m2/liter (p less than 0.05). In contrast, nitroprusside decreased left ventricular end-diastolic volume index from 57 +/- 16 to 41 +/- 10 ml/m2 (p less than 0.05), cardiac index from 3.2 +/- 0.7 to 2.8 +/- 0.6 liters/min per m2 (p less than 0.05) and stroke volume index from 28 +/- 6 to 24 +/- 5 ml/m2 (p less than 0.01), with no change in systemic vascular resistance index (40 +/- 10 mm Hg.min.m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Beta-adrenergic stimulation with isoproterenol enhances left ventricular diastolic performance in hypertrophic cardiomyopathy despite potentiation of myocardial ischemia. Comparison to rapid atrial pacing.

Impaired left ventricular relaxation and filling is an important pathophysiologic mechanism in hypertrophic cardiomyopathy. To determine whether isoproterenol, known to improve relaxation in isolated cardiac muscle, could favorably modify this effect, we assessed simultaneous left ventricular volume and regional systolic asynchrony (by radionuclide angiography), left ventricular pressure (by micromanometer catheters), and lactate metabolism in 12 patients with hypertrophic cardiomyopathy. Pressure-volume relations were studied during atrial pacing stress to induce myocardial ischemia and during isoproterenol infusion to similar heart rates. Angina occurred in 10 patients with pacing and in 11 patients during isoproterenol infusion; lactate consumption was reduced in nine patients during isoproterenol compared with pacing, including five patients who produced lactate with isoproterenol. During isoproterenol compared with pacing, peak left ventricular pressure was higher (205 +/- 33 vs. 142 +/- 21 mm Hg, p less than 0.001), ejection fraction was higher (77 +/- 10% vs. 71 +/- 12%, p less than 0.02), and regional systolic nonuniformity was diminished. Despite ischemia, these changes in load and nonuniformity during isoproterenol were associated with enhanced diastolic function compared with pacing tachycardia: isoproterenol reduced T 1/2, the half-time of pressure decline after peak negative dP/dt (from 46 +/- 10 to 33 +/- 6 msec, p less than 0.001), shifted the diastolic pressure-volume curve downward and rightward in 10 of 12 patients, and increased end-diastolic volume (from 77 +/- 18% to 100 +/- 11% of control values, p less than 0.001) with no change in end-diastolic pressure (19 +/- 7 to 19 +/- 5 mm Hg, p = NS). Thus, despite ischemia, isoproterenol improved left ventricular relaxation and filling compared with tachycardia in the absence of beta-adrenergic stimulation. Although isoproterenol is detrimental in hypertrophic cardiomyopathy by provoking ischemia, these data suggest that the adverse effects of ischemia on ventricular relaxation and distensibility may be alleviated by beta-adrenergic stimulation, possibly as a result of enhanced inactivation and restored load sensitivity.

Adult↗