Publications
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Lahiri A, Senior R, 1998, Evolving therapeutic concepts and imaging in ischemic cardiomyopathy., J Nucl Cardiol, Vol: 5, Pages: 598-608, ISSN: 1071-3581
Basu S, Senior R, Raval U, et al., 1997, Superiority of nitrate-enhanced 201Tl over conventional redistribution 201Tl imaging for prognostic evaluation after myocardial infarction and thrombolysis., Circulation, Vol: 96, Pages: 2932-2937, ISSN: 0009-7322
BACKGROUND: 201Tl imaging has been widely used for postinfarction risk stratification. However, thrombolytic therapy and aspirin have significantly changed outcome, and there are few nuclear imaging studies that assess prognosis in such patients. Furthermore, newer techniques of 201Tl imaging, such as reinjection and nitrate-enhanced rest 201Tl imaging, have been shown to improve the detection of viable but jeopardized myocardium. METHODS AND RESULTS: We studied 100 consecutive patients, who remained event free 6 weeks after myocardial infarction and thrombolysis. Patients underwent conventional exercise and 4-hour redistribution imaging, followed on a separate day by nitrate-enhanced rest 201Tl study. Planar images were reported semiquantitatively by two experienced observers blinded to clinical data. Redistribution and rest injection images were classified as demonstrating reversible ischemia if they showed improvement in uptake by at least two grades in at least two segments in comparison with the initial exercise scintigram. Patients were followed up for 8 to 32 months (mean, 21 months); during this period, 37 patients had first cardiac events. Reversible ischemia was present in 29 patients on redistribution, of whom 14 (48%) had events; of 71 without reversible defects, 23 (32%) had events (hazard ratio, 1.5; 95% CI, 0.8 to 3.0; P=NS). Nitrate-enhanced rest 201Tl imaging detected reversible defects in 68 patients, of whom 33 (49%) had events, whereas of 32 without reversible defects, only 4 (13%) had subsequent cardiac events (hazard ratio, 8.1; 95% CI, 2.7 to 23.8; P<.001). CONCLUSIONS: Thus, after myocardial infarction and thrombolysis, even "stable" patients have a high (68%) incidence of viable but jeopardized myocardium, causing a high event rate. Those identified to be at high risk by perfusion imaging may benefit from early intervention.
Suleiman K, Desai D, Raval U, et al., 1997, The effect of training on the interpretation of 99Tcm-sestamibi myocardial perfusion SPET in patients with suspected coronary artery disease., Nucl Med Commun, Vol: 18, Pages: 922-926, ISSN: 0143-3636
The aim of this study was to examine the effect of a period of concentrated training in nuclear cardiology on the accuracy of reporting 99Tcm-sestamibi (99Tcm-MIBI) single photon emission tomographic (SPET) images. Two visiting cardiologists, with no previous experience in nuclear cardiology, were asked to report blindly 60 99Tcm-MIBI SPET scans after 2 weeks of training in nuclear cardiology. One (observer 2) reported the same scans blindly after 2 months of further training. The results were compared with the assessment made by two experienced nuclear cardiologists and by using kappa statistics. Kappa values for the overall interpretation of the scan (normal or abnormal), segmental analysis (normal, ischaemic, fixed or mixed) and the three arterial territories were 0.7, 0.58 and 0.67 respectively. Following 2 months of further intensive training of observer 2, the kappa values were 0.857, 0.78 and 0.91 respectively. The difference between the two readings of observer 2 was significantly different for the segmental analysis (P < 0.001) and arterial territories (P = 0.006) but it did not reach statistical significance for the overall interpretation (P = 0.7). Thus, cardiologists without previous interpretation skills in nuclear cardiology required about 2 months of intensive training to achieve good accuracy in the interpretation of 99Tcm-MIBI SPET images. Accordingly, these techniques can be established in centres other than tertiary sites.
Senior R, Kenny A, Nihoyannopoulos P, 1997, Stress echocardiography for assessing myocardial ischaemia and viable myocardium., Heart, Vol: 78 Suppl 1, Pages: 12-18, ISSN: 1355-6037
Basu S, Senior R, Raval U, et al., 1997, Beneficial effects of intravenous and oral carvedilol treatment in acute myocardial infarction. A placebo-controlled, randomized trial., Circulation, Vol: 96, Pages: 183-191, ISSN: 0009-7322
BACKGROUND: Evidence of efficacy and safety of beta-blockers after thrombolysis for acute myocardial infarction (AMI) is equivocal. Newer beta-blockers such as carvedilol have not been tested in this setting. METHODS AND RESULTS: This study investigated the effects of acute (intravenous) and long-term (6 months, oral) treatment with carvedilol versus placebo in 151 consecutive patients with AMI. Exercise ECG, ambulatory monitoring, and two-dimensional echocardiography were performed before hospital discharge and at 3 and 6 months. All patients were followed up and cardiovascular events recorded. The Cox proportional hazards model was used to compare time from randomization with the occurrence of a cardiovascular event, and Kaplan-Meier survival curves were calculated. Carvedilol was found to be safe, and it significantly reduced cardiac events compared with placebo (18 on carvedilol and 31 on placebo, P < .02). Fifty-four patients had heart failure at study entry; 34 received carvedilol. There were no adverse effects of carvedilol therapy and no excess events in this subgroup. Carvedilol produced significant reductions in heart rate (P < .0001), blood pressure (P < .005) at rest, and rate-pressure product at peak exercise (P < .003), but exercise capacity was unchanged. Left ventricular ejection fraction was not altered significantly by carvedilol, but stroke volume was higher at pre-hospital discharge examination (63 versus 53 mL; P < .01). Diastolic filling of the left ventricle (E/A ratio) was also improved (1.2 versus 0.9; P < .001). In a subgroup with left ventricular ejection fraction < 45% (n = 49 patients; 24 on carvedilol and 25 on placebo), carvedilol showed attenuation of remodeling. CONCLUSIONS: Carvedilol was well tolerated and safe to use in patients immediately after AMI, including those with heart failure, and significantly improved outcome.
Khattar RS, Acharya DU, Kinsey C, et al., 1997, Longitudinal association of ambulatory pulse pressure with left ventricular mass and vascular hypertrophy in essential hypertension., J Hypertens, Vol: 15, Pages: 737-743, ISSN: 0263-6352
OBJECTIVE: To determine the longitudinal relationship between clinic and ambulatory blood pressures and subsequent left ventricular and carotid artery structure. DESIGN: A retrospective follow-up study. SETTING: A large district general hospital in Harrow, UK. PATIENTS: One hundred and forty patients who had been subjected to 24 h ambulatory intra-arterial blood pressure monitoring on the basis of their having an elevated clinic blood pressure were followed up randomly a mean of 9.4 +/- 3.4 years later. The ambulatory blood pressure parameters measured were the mean systolic, mean diastolic and mean pulse pressures. Follow-up variables assessed included the clinic blood pressure, body mass index, total cholesterol, number of years of follow-up, left ventricular mass index, carotid intima-media thickness and carotid artery cross-sectional area. MAIN OUTCOME MEASURES: The left ventricular mass index, carotid intima-media thickness and carotid artery cross-sectional area. RESULTS: The mean pulse pressure and mean systolic blood pressure were correlated significantly with the left ventricular mass index (r = 0.46, P < 0.001 and r = 0.36, P < 0.001, respectively), carotid intima-media thickness (r = 0.45, P < 0.001 and r = 0.37, P < 0.001, respectively) and carotid artery cross-sectional area (r = 0.46, P < 0.001 and r = 0.41, P < 0.001, respectively). The mean pulse pressure was associated independently with all three outcome measures. In addition, the body mass index was an independent determinant of the left ventricular mass index, whereas the serum cholesterol level was associated independently with the carotid artery cross-sectional area; the number of years of follow-up was related independently to the left ventricular mass index and carotid intima-media thickness, but not to the cross-sectional area. CONCLUSIONS: These findings suggest that ambulatory blood pressure monitoring can play a role in guiding the choice of doses in drug therapy to limi
Senior R, Soman P, Khattar RS, et al., 1997, Prognostic value of dobutamine stress echocardiography in patients undergoing diagnostic coronary arteriography., Am J Cardiol, Vol: 79, Pages: 1610-1614, ISSN: 0002-9149
There are only a few studies addressing the prognostic value of dobutamine stress echocardiography in patients with suspected coronary artery disease and none have assessed its value compared with coronary arteriography. Accordingly, graded dobutamine stress echocardiography was performed in 121 patients who underwent coronary arteriography based on symptoms and the findings of treadmill exercise electrocardiography. During the follow-up period of mean (SD) months (15 +/- 9) there were 41 cardiac events (death [n = 5], acute myocardial infarction [n = 2], unstable angina [n = 29], and congestive heart failure [n = 5]). There were a greater number of patients with inducible wall motion abnormality (88%) on dobutamine stress with cardiac events compared with those without (55%, p <0.001). The wall motion score indexes at rest (1.6 +/- 0.6) and at peak stress (2.1 +/- 0.8) were worse in patients with cardiac events compared with those without (1.2 +/- 0.3, p <0.001 and 1.5 +/- 0.6, p <0.001, respectively). When multivariate analysis was performed using clinical, exercise, echocardiographic, and coronary arteriographic data the independent predictors of cardiac events were exercise duration (p = 0.01), presence of inducible wall motion abnormality (p = 0.03), and wall motion score index at peak stress (p <0.001). Thus, dobutamine stress echocardiography is a powerful predictor of future cardiac events in patients undergoing exercise testing and coronary arteriography for evaluation of chest pain and is superior to both exercise electrocardiography and coronary arteriography for the prediction of subsequent cardiac events.
Soman P, Senior R, 1997, Severe ventricular dysfunction secondary to subarachnoid hemorrhage., Clin Cardiol, Vol: 20, Pages: 402-403, ISSN: 0160-9289
A 39-year-old man was brought to the emergency department in a coma. The electrocardiogram showed partial left bundle-branch block and ST elevation in precordial leads, and serum creatinine kinase activity was elevated. Two-dimensional echocardiography revealed severe biventricular dysfunction. Autopsy demonstrated the presence of subarachnoid hemorrhage. Coronary arteries and the myocardium were macroscopically normal.
Khattar RS, Senior R, Joseph D, et al., 1997, Comparison of arbutamine stress 99mTc-labeled sestamibi single-photon emission computed tomographic imaging and echocardiography for detection of the extent and severity of coronary artery disease and inducible ischemia., J Nucl Cardiol, Vol: 4, Pages: 211-216, ISSN: 1071-3581
BACKGROUND: Arbutamine is a new synthetic catecholamine developed specifically for pharmacologic stress testing. METHODS AND RESULTS: We investigated 39 patients undergoing coronary arteriography to compare arbutamine stress (99m)Tc-labeled sestamibi single-photon emission computed tomographic imaging and echocardiography for detection of the extent and severity of coronary artery disease and inducible ischemia. Rest and stress studies were analyzed blindly according to a 12-segment left ventricular model for both techniques. Each segment was graded according to severity of wall thickening abnormality and perfusion defect (1 = normal to 4 = severe). Total perfusion defect and wall thickening scores were calculated at peak stress and the difference in scores between stress and rest (delta perfusion defect; delta wall thickening) were used as indexes of inducible ischemia. Twenty-one patients had multivessel disease, nine had single-vessel disease, and nine had normal coronary arteries. Diagnostic accuracies for the detection of coronary artery disease for single-photon emission computed tomographic imaging and echocardiography were 95% and 92%, respectively. Extent and severity of coronary artery disease indicated by a peak stress perfusion defect score of 26 +/- 6.4 and wall thickening score of 25.1 +/- 8.4 were similar, and there was no significant difference in the delta perfusion defect and delta wall thickening scores of 8.7 +/- 5.5 and 10.4 +/- 7.1, respectively. Segmental concordance rates for the detection of coronary artery disease and inducible ischemia were 74% (K = 0.47; confidence interval 0.39 to 0.55) and 74% (kappa = 0.42; confidence interval 0.34 to 0.51), respectively. Regional concordance for coronary artery disease was 84% (kappa = 0.68; confidence interval 0.51 to 0.84). Where discordance was present, there was a greater prevalence of perfusion abnormality compared with wall thickening abnormality. CONCLUSION: Arbutamine stress single-photon emis
Soman P, Khattar R, Senior R, et al., 1997, Inotropic stress with arbutamine is superior to vasodilator stress with dipyridamole for the detection of reversible ischemia with Tc-99m sestamibi single-photon emission computed tomography., J Nucl Cardiol, Vol: 4, Pages: 364-371, ISSN: 1071-3581
BACKGROUND: There is a paucity of data comparing the relative merits of inotropic and vasodilator stress Tc-99m sestamibi single-photon emission computed tomography (SPECT) for the detection of coronary artery disease and reversible ischemia. METHODS AND RESULTS: Twenty-seven patients referred for diagnostic coronary arteriography underwent separate day dipyridamole and arbutamine Tc-99m sestamibi SPECT imaging with simultaneous two-dimensional echocardiography. The sensitivity of arbutamine and dipyridamole Tc-99m sestamibi for the detection of coronary artery disease was 100% (21 of 21) and 90% (19 of 21), respectively, with a specificity of 66% (4 of 6) for both. Coronary artery disease was detected in all six patients with single vessel disease by both stress modalities. The sensitivity for prediction of multivessel disease was 66% (10 of 15) for arbutamine and 46% (7 of 15) for dipyridamole stress. Arbutamine stress induced a greater extent and severity of perfusion abnormality at peak stress (peak perfusion score 25 +/- 6.2 and 21 +/- 5.9 for arbutamine and dipyridamole, respectively, p = 0.001) and reversible perfusion defects (difference between peak stress and rest scores 8.8 +/- 5.5 and 5.2 +/- 4.4 for arbutamine and dipyridamole, respectively, p = 0.001). Furthermore a significantly higher percentage of reversible defects induced by arbutamine stress was associated with wall thickening abnormality on simultaneous echocardiography, which is a more specific marker of myocardial ischemia (88% and 24% for arbutamine and dipyridamole, respectively, p = 0.002). CONCLUSION: Inotropic stress may be superior to vasodilators for the determination of the extent and severity of myocardial involvement and reversible ischemia by Tc-99m sestamibi SPECT.
Senior R, Raval U, Lahiri A, 1996, Prognostic value of stress dobutamine technetium-99m sestamibi single-photon emission computed tomography (SPECT) in patients with suspected coronary artery disease., Am J Cardiol, Vol: 78, Pages: 1092-1096, ISSN: 0002-9149
Inotropic stress using graded dobutamine infusion has evolved as an alternative form of pharmacologic stress in conjunction with perfusion and functional imaging for evaluation of coronary heart disease. However, the prognostic value of technetium-99m (Tc-99m) sestamibi single-photon emission computed tomography (SPECT) imaging in patients undergoing dobutamine stress testing for the detection of coronary artery disease is unclear. Accordingly, 61 patients undergoing coronary arteriography for the evaluation of chest pain on the basis of symptoms and treadmill exercise electrocardiography underwent SPECT imaging at rest and during stress. Patients were followed up for 19 +/- 11 months (2 to 33) during which 2 died, 2 had acute myocardial infarction, 13 developed unstable angina, and 3 had congestive heart failure. Univariate Cox regression analysis revealed that those with reversible defects (95%) and defects in multiple vascular territories (80%) on SPECT had a greater number of cardiac events compared to those without (59% [p = 0.02] and 34% [p = 0.002], respectively). The number of reversible (3.9 +/- 2.1) and fixed (2.3 +/- 2.0) segments (12-segment model) were greater in patients with cardiac events compared to those without, (2.3 +/- 2.5, p = 0.009 and 1.1 +/- 2.0, p = 0.02) respectively. When multivariate analysis was performed using clinical, exercise testing, and SPECT variables, the independent predictors of cardiac events were a history of myocardial infarction (p <0.001), number of reversible segments (p = 0.001), and presence of defects in multiple vascular territories (p = 0.01). In summary, dobutamine stress Tc-99m sestamibi SPECT is a powerful predictor of future cardiac events in patients undergoing coronary arteriography for evaluation of chest pain and may be used to stratify patients for further intervention.
Basu S, Senior R, Dore C, et al., 1996, Value of thallium-201 imaging in detecting adverse cardiac events after myocardial infarction and thrombolysis: A follow up of 100 consecutive patients, BMJ-BRITISH MEDICAL JOURNAL, Vol: 313, Pages: 844-848, ISSN: 1756-1833
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Sridhara BS, Senior R, Anagnostou E, et al., 1996, Saterinone: A New Dual-Action Drug in the Acute Management of Chronic Heart Failure., Am J Ther, Vol: 3, Pages: 597-601
A new dual-action drug called saterinone combines both alpha-1 blocking vasodilatory property and phosphodiesterase III inhibition--mediated inotropism. A placebo-controlled, randomized, double-blind study was performed in 12 patients with severe congestive heart failure. Either 2 &mgr;g center dot kg center dot min(minus sign1) saterinone (n = 8) or placebo (n = 4) was injected intravenously over 3 h at rest. On-line hemodynamic measurement utilizing intra-arterial blood pressure monitoring and two-dimensional (2D) echocardiography were performed at basal time; then 30, 60, 120 and 180 min after infusion. The parameters measured were blood pressure (mmHg), systemic vascular resistance (SVR dynes center dot cm(5) center dot min(minus sign1)), pulmonary artery pressure (PAP mmHg), mean pulmonary capillary wedge pressure (PCWP mmHg) and cardiac index (CI 1 min/m(2)) using right heart catheterization and end-systolic volume (ESV ml) and end-diastolic volumes (EDV ml), ejection fraction (EF%) using 2D echocardiography. Placebo had no significant effects on any of the parameters (p = NS). Saterinone decreased SVR by 37% (p < 0.001), PAPm by 24% (p < 0.05), PCWP by 35% (p < 0.05), ESV by 27% (p < 0.01) and increased CI by 32% (p < 0.05) and EF by 45% (p < 0.05). Saterinone appears to be a potent drug that produces improvements in both cardiac hemodynamics and LV functional parameters. Further study with this interesting agent is indicated.
Khattar RS, Basu SK, Raval U, et al., 1996, Prognostic value of predischarge exercise testing, ejection fraction, and ventricular ectopic activity in acute myocardial infarction treated with streptokinase., Am J Cardiol, Vol: 78, Pages: 136-141, ISSN: 0002-9149
The relative importance of prognostic parameters that delineate left ventricular function, myocardial ischemia, and arrhythmogenic potential after thrombolytic therapy is not clear. This study investigated 112 patients with acute myocardial infarction who were treated with thrombolysis to determine the relative prognostic value of predischarge treadmill exercise testing, radionuclide ventriculography, and ambulatory electrocardiographic monitoring for ventricular ectopic activity. During a mean follow-up period of 18 months (range 6 to 30), 42 first cardiac events were recorded, consisting of 3 deaths, 6 reinfarctions, 16 bouts of unstable angina, 16 episodes of heart failure, and 1 arrhythmic event. Univariate analysis revealed ejection fraction, exercise time, and ventricular ectopic count of > or = 10/hour to be predictive of future cardiac events. Subsequent multivariate analysis showed ejection fraction (p <0.001) and exercise time (p=0.002 to have independent prognostic value, but ventricular ectopic activity did not provide additional information. Ventricular ectopic count > or = 10/hour was additionally predictive only when combined with either ejection fraction (R2=5.4%) or exercise time (R2=2.9%). Event-free survival analysis revealed hazard ratios for ejection fraction <40% and exercise time <7 minutes of 3.63 (p=0.001) and 2.16 (p=0.01), respectively. Although ejection fraction and exercise time were able to predict future episodes of heart failure, neither could adequately identify patients at risk of recurrent ischemic events.
Senior R, Basu S, Handler C, et al., 1996, Diagnostic accuracy of dobutamine stress echocardiography for detection of coronary heart disease in hypertensive patients., Eur Heart J, Vol: 17, Pages: 289-295, ISSN: 0195-668X
To compare the diagnostic accuracy between dobutamine echocardiography and treadmill exercise electrocardiography in detecting coronary artery disease in hypertensive patients, 43 patients without electrocardiographic evidence of left ventricular hypertrophy and basal ST-T changes, who had also undergone coronary angiography, were further evaluated by dobutamine echocardiography. The patients also underwent treadmill exercise echocardiography. Left ventricular mass index was calculated by echocardiography. Twenty-nine patients had coronary artery disease, of whom 22 had multi-vessel disease and 14 a normal coronary anatomy. Twenty-eight patients had an increased left ventricular mass index. The sensitivities of dobutamine echocardiography and exercise electrocardiography for detecting coronary artery disease were 93% and 72% (P = 0.08), respectively, and the specificities were 100% and 29% (P < 0.005), respectively. Logistic regression analysis showed exercise electrocardiography to be a poor predictor of coronary artery disease (P < 0.09) but dobutamine echocardiography was significantly better (P < 0.001). When patients with increased left ventricular mass index were excluded, prediction of coronary anatomy by exercise electrocardiography improved only marginally (p = 0.4) while dobutamine echocardiography was significantly better (P < 0.001). Thus dobutamine echocardiography is superior to exercise electrocardiography for diagnosis of coronary artery disease in hypertensive patients.
Senior R, Glenville B, Basu S, et al., 1995, Dobutamine echocardiography and thallium-201 imaging predict functional improvement after revascularisation in severe ischaemic left ventricular dysfunction., Br Heart J, Vol: 74, Pages: 358-364, ISSN: 0007-0769
OBJECTIVES: To evaluate the concordance between thallium-201 uptake and echocardiographic wall thickening, which are both indicators of potentially reversible myocardial dysfunction, in patients with chronic ischaemic left ventricular failure and to assess their relative contribution to predicting improvement in regional function after revascularisation in a subgroup. PATIENTS AND METHODS: 45 patients with chronic ischaemic left ventricular dysfunction (mean (SD) ejection fraction 25 (8)%) underwent echocardiography before and after dobutamine infusion (10 micrograms/kg/min). Of these, 22 patients underwent rest echocardiography at a mean (SD) of 9 (1) weeks after revascularisation. 201Tl imaging was performed during dobutamine echocardiography and at rest, 1, and 4 h after treatment with sublingual glyceryl trinitrate on two separate days. Potentially reversible dysfunction was thought to be present when a myocardial segment contained a Tl score of > or = 3 (ascending score 1-4), or showed improved wall thickening of a dysynergic segment during dobutamine stimulation. RESULTS: Of the 201Tl protocols, the redistribution scan 1 h after treatment with glyceryl trinitrate best demonstrated myocardial viability. Concordance between 201Tl and dobutamine induced wall thickening was 82% (kappa = 0.59) for detecting potentially reversible myocardial dysfunction before revascularisation (n = 45). Regional function improved in 18 of 22 patients after revascularisation. There were 168 dysynergic segments before intervention. The sensitivity of echocardiography and 201Tl imaging for detecting "recoverable" or viable segments after revascularisation was 87% and 92% respectively and specificity was 82% and 78% respectively (P = NS). CONCLUSIONS: Dobutamine echocardiography and 201Tl imaging may be used to predict mechanical improvement in dysynergic segments after revascularisation in patients with chronic ischaemic left ventricular dysfunction.
Bhattacharya S, Jordan R, Machin S, et al., 1995, Blockade of the human platelet GPIIb/IIIa receptor by a murine monoclonal antibody Fab fragment (7E3): potent dose-dependent inhibition of platelet function., Cardiovasc Drugs Ther, Vol: 9, Pages: 665-675, ISSN: 0920-3206
The platelet glycoprotein (GP) IIb/IIIa receptor can bind fibrinogen, von Willebrand factor, and other adhesive ligands; this binding is the final common pathway mediating platelet aggregation. The purpose of this study was to evaluate the safety and platelet inhibitory characteristics of the Fab fragment of the murine monoclonal anti-GPII/IIIa 7E3 antibody (m7E3 Fab) when administered intravenously as a single bolus dose, as a single and repeat bolus dose, and as a single bolus dose followed by continuous infusions of varying duration. Various dosage regimens of m7E3 Fab were studied in 74 patients with stable angina. Dosage regimens included single doses of m7E3 Fab from 0.1 to 0.3 mg/kg, a single dose of 0.20-0.30 mg/kg, and a repeat dose of 0.05 mg/kg, or a loading dose followed by a continuous infusion of m7E3 Fab for up to 36 hours. To assess the effect of m7E3 Fab on platelet function, quantitative blockade of GPIIb/IIIa receptors, inhibition of ex vivo platelet aggregation, and template bleeding time were measured in all patients. Dose-dependent inhibition of platelet function was evident in response to escalating bolus doses of m7E3 Fab, with maximum inhibition observed at 0.25-0.30 mg/kg body weight; at the 0.30 mg/kg dose, mean (+/- SE) GPIIb/IIIa receptor blockade was 81 +/- 3%, ex vivo platelet aggregation in response to 20 microM ADP was 14 +/- 6% of baseline, and the median bleeding time was > 20 minutes. Although platelet function gradually recovered following a single bolus injection, platelet inhibition could be sustained by continuous, low-dose infusion of the antibody. Platelet inhibition occurred within minutes, but m7E3 Fab that did not bind to platelets cleared rapidly from circulation. Sixteen percent of the m7E3 Fab-injected subjects exhibited low titer, human anti-murine antibody responses. No significant bleeding or allergic reactions were observed in any patients. One of the 74 patients developed transient thrombocytopenia soon after r
Senior R, Lahiri A, 1995, Enhanced detection of myocardial ischemia by stress dobutamine echocardiography utilizing the "biphasic" response of wall thickening during low and high dose dobutamine infusion., J Am Coll Cardiol, Vol: 26, Pages: 26-32, ISSN: 0735-1097
OBJECTIVES: We sought to assess the ability of the "biphasic" response (i.e., initial improvement in wall thickening followed by reduced wall thickening) during serial dobutamine stress echocardiography to detect ischemia in patients with a wall motion abnormality. Furthermore, we compared the power of the biphasic echocardiographic response with that of myocardial perfusion imaging for the detection of myocardial ischemia. BACKGROUND: Stress echocardiography has been shown to be less sensitive than radionuclide perfusion imaging for detecting ischemia in patients with a wall motion abnormality. Peak stress wall thickening in such areas may not give a full account of the intermediate changes, whereas initial improvement (the biphasic response) may enhance diagnosis. METHODS: Patients with a wall motion abnormality and documented coronary artery disease underwent simultaneous graded dobutamine (5 to 40 micrograms/kg body weight per min) stress echocardiography and radionuclide perfusion imaging with single-photon emission computed tomography using either technetium-99m sestamibi or technetium-99m tetrofosmin. Semiquantitative analyses of image groups were performed in blinded manner by two separate groups of observers. RESULTS: Myocardial ischemia was detected by perfusion imaging in 45 of the 54 patients. High dose dobutamine echocardiography detected ischemia in only 25 (56%) of these patients. However, when the biphasic response was taken into account, ischemia was detected in 44 (98%) of the 45 patients (p < 0.001). Agreement between radionuclide imaging and echocardiographic findings for the detection of ischemia was significantly enhanced (p = 0.03) when the biphasic response was used (89%, kappa = 0.51) instead of high dose stress dobutamine echocardiography (56%, kappa = 0.10). CONCLUSIONS: The detection of myocardial ischemia may be significantly enhanced by utilizing the biphasic response during serial stress dobutamine echocardiography in pati
Murray JG, Brown AL, Anagnostou EA, et al., 1995, Widening of the tracheal bifurcation on chest radiographs: value as a sign of left atrial enlargement., AJR Am J Roentgenol, Vol: 164, Pages: 1089-1092, ISSN: 0361-803X
OBJECTIVE: This study evaluated widening of the tracheal bifurcation (subcarinal and interbronchial) angle on posteroanterior chest radiographs as a sign of left atrial enlargement. The purpose was to determine the diagnostic sensitivity and specificity of the sign. MATERIALS AND METHODS: The chest radiographs and echocardiograms of 122 clinically stable patients were retrospectively reviewed. The mean interval between examinations was 10 days (range, 0-30 days). The left atrial dimension was measured on the two-dimensional echocardiograms. Sixty-five patients had a normal left atrial dimension (mean, 34 mm), and 45 patients had an enlarged atrium (mean, 47 mm) on echocardiography. Subcarinal and interbronchial angles were jointly measured by two observers who were unaware of the echocardiographic findings. Correlation analysis was used to determine which angle measurement best predicted the left atrial size. Discriminant analysis was used to derive a threshold angle that predicted left atrial enlargement. RESULTS: The carina was inadequately seen on 14 radiographs. Left atrial size correlated poorly with both the interbronchial (r = .33) and the subcarinal (r = .25) angel values. An interbronchial angle of 76.4 degrees and a subcarinal angle of 65.4 degrees were the best discriminators between patients with normal and those with enlarged left atrial dimensions (sensitivities, 61% and 51%, respectively; specificities, 63% and 66%). CONCLUSION: Our findings show that widening of the tracheal bifurcation angle on chest radiographs is an insensitive and nonspecific sign of left atrial enlargement. This sign is of little value in diagnosing left atrial enlargement.
Senior R, Raval U, Lahiri A, 1995, Technetium 99m-labeled sestamibi imaging reliably identifies retained contractile reserve in dyssynergic myocardial segments., J Nucl Cardiol, Vol: 2, Pages: 296-302, ISSN: 1071-3581
BACKGROUND: Recently there has been considerable controversy regarding the use of 99mTc-labeled sestamibi as an agent for the detection of viable myocardium. In this study we have used dobutamine-induced left ventricular wall thickening by echocardiography in regions with evidence of resting dyssynergy of the left ventricle as an indicator of retained contractile reserve and compared this with 99m Tc-labeled sestamibi uptake in the same regions. METHODS AND RESULTS: Twenty-seven patients with documented coronary artery disease and severe regional wall motion abnormalities underwent low-dose (5 to 15 micrograms/kg/min) dobutamine echocardiography and maximal (15 to 40 micrograms/kg/min) stress dobutamine 99mTc-labeled sestamibi single-photon emission computed tomographic imaging. Separate-day rest 99mTc-labeled sestamibi scanning was also performed. 99mTc-labeled sestamibi uptake was assessed semiquantitatively from grades from 1 to 4, from normal to absent perfusion. Regions with grade 3 or less uptake were considered viable by 99mTc-labeled sestamibi. Of the 34 regions with severe wall motion abnormalities by echocardiography, 32 showed improved wall thickening with low-dose dobutamine. Rest 99mTc-labeled sestamibi detected retained myocardial viability in 29 of these regions (91%) that were deemed to have contractile reserve by echocardiography (concordance: 91% [K = 0.53; p < 0.001]). Furthermore, stress-rest 99mTc-labeled sestamibi revealed completely reversible defects in five regions (16%), partially reversible defects in 24 regions (75%), and grade 4 uptake and fixed (nonviable) defects in three (9%) of these 32 regions with retained contractile reserve. CONCLUSION: Uptake of 99mTc-labeled sestamibi at rest accurately identifies regions of segmental dyssynergy in which recovery of function may be provoked by inotropic stimulation. Addition of stress dobutamine 99mTc-labeled sestamibi provides further proof of retained myocardial viability in these dysfunct
Senior R, Sridhara BS, Anagnostou E, et al., 1994, Synergistic value of simultaneous stress dobutamine sestamibi single-photon-emission computerized tomography and echocardiography in the detection of coronary artery disease., Am Heart J, Vol: 128, Pages: 713-718, ISSN: 0002-8703
The relative value of exercise electrocardiography, simultaneous dobutamine technetium 99m-sestamibi (MIBI) single-photon-emission computerized tomography (SPECT), and echocardiography were evaluated for the diagnosis of coronary artery disease in patients with chest pain. Sixty-one consecutive patients underwent exercise electrocardiography and simultaneous graded dobutamine echocardiography and MIBI imaging. All patients underwent coronary arteriography. The exercise electrocardiogram was found to be a poor predictor of coronary artery disease (p not significant). Individually, MIBI SPECT and echocardiography were significantly predictive of coronary artery disease (p < 0.001). According to logistic regression analysis, the combined imaging modalities significantly increased the prediction of coronary artery disease for any vessel (p < 0.001), for multiple vessels (p < 0.001), and for the left anterior descending (p < 0.001), for right coronary artery (p < 0.001), and for left circumflex arteries (p < 0.01), compared with either MIBI SPECT or echocardiography alone. The results suggest a synergism in the detection of coronary artery disease when MIBI SPECT and echocardiography are combined during dobutamine stress.
Sridhara BS, Dudzic E, Basu S, et al., 1994, Reverse redistribution of thallium-201 represents a low-risk finding in thrombolysed patients following myocardial infarction., Eur J Nucl Med, Vol: 21, Pages: 1094-1097, ISSN: 0340-6997
The aim of the study was to evaluate the prevalence and clinical significance of reverse redistribution on thallium-201 imaging in post-myocardial infarction patients who have undergone thrombolytic therapy. Sixty-two patients aged 35-79 (mean 60) years with proven myocardial infarction who had undergone thrombolysis were studied 6 weeks post infarction. Standard stress and 4-h redistribution imaging was performed with 201Tl following treadmill exercise. Separate day rest injection of 201Tl was given after sublingual nitroglycerine; imaging was performed at 1 h. Planar images were acquired in three standard views and semiquantitative segmental analysis of the images was performed from the unprocessed images. All patients had radionuclide ventriculography for the assessment of left ventricular ejection fraction and wall motion abnormality. Thirty-three patients also had coronary angiography. 201Tl scintigraphy revealed fixed defects in 19 patients, reversible defects in 22, and reverse redistribution in 21. Those with reverse redistribution had a significantly higher exercise capacity (P < 0.01). Mean (SD) left ventricular ejection fraction was 46 (12)% for those with fixed defects, 47 (9)% for those with reversible defects and 45 (15)% for patients with reverse redistribution (P = NS). The regional wall motion abnormality score was 8 (5), 11.8 (2.2) and 14.2 (6) respectively in patients with reverse redistribution, redistribution alone and fixed defects. Regions with reverse redistribution revealed less regional wall motion abnormality compared to the other two groups (P < 0.01). Fifteen patients demonstrated significant 201Tl uptake in the region showing reverse redistribution, with rest injection of 201Tl following sublingual nitroglycerine, suggesting viable myocardium in that region.(ABSTRACT TRUNCATED AT 250 WORDS)
Senior R, Sridhara BS, Basu S, et al., 1994, Comparison of radionuclide ventriculography and 2D echocardiography for the measurement of left ventricular ejection fraction following acute myocardial infarction., Eur Heart J, Vol: 15, Pages: 1235-1239, ISSN: 0195-668X
To compare the measurement of left ventricular ejection fraction obtained by two-dimensional echocardiography and by radionuclide ventriculography in patients following acute myocardial infarction, 49 consecutive patients with acute myocardial infarction underwent echocardiography and radionuclide ventriculography on the same day, pre-discharge. Left ventricular ejection fraction was assessed by two blinded observers for each method and reproducibility was also assessed for each technique. The limits of agreement for the differences in ejection fraction (%) between the two methods was--11.4, 12.2; the mean difference 0.4 was not significantly different from zero. The limits of agreement for the intra- and inter-observer differences in ejection fraction by radionuclide ventriculography were--9.4, 7.6 and -8.6, 11.0, respectively; the mean differences--0.9 and 1.2 were not significantly different from zero. The limits of agreement for the intra- and inter-observer differences by echocardiography were--5.8, 6.6 and--8.9, 9.5 respectively; the mean differences 0.4 and 0.3 were not significantly different from zero. Thus, two-dimensional echocardiography compares well with radionuclide ventriculography for the assessment of ejection fraction without the disadvantage of radiation.
Acharya DU, Senior R, Basu S, et al., 1994, Anti-ischaemic and haemodynamic effects of elgodipine, a potent new generation calcium antagonist, in chronic stable angina., Eur Heart J, Vol: 15, Pages: 665-671, ISSN: 0195-668X
The effects of oral elgodipine, a new dihydropyridine calcium antagonist on ischaemia and left ventricular function were assessed by a single blind placebo controlled study in 12 patients with chronic stable angina. Graded treadmill exercise and echocardiography/Doppler were performed before and 90 min after single oral doses of elgodipine of 20 mg, 40 mg and 60 mg, or placebo, given at weekly intervals. Elgodipine significantly increased exercise time by 1.1, 2.0 and 2.4 min, (P < 0.001 in each case) and time to onset of angina by 1.1 (P < 0.01), 1.9 (P < 0.001) and 2.6 min (P < 0.001) with increasing doses of the drug. Angina was abolished in 50% of patients with significant improvement in ST depression at peak exercise (P < 0.001) with the 60 mg dose. Blood pressure fell significantly at rest and peak exercise with a corresponding significant increase in heart rate. Ejection fraction was increased by 7.8% (P < 0.001) and 8.4% (P < 0.001) as was the stroke volume by 9.3 ml (P < 0.001) and 12.5 ml (P < 0.001) at 40 mg and 60 mg respectively. Peak mitral A to E velocity ratio and total peripheral resistance decreased significantly in a dose related linear trend. Only minor side effects were noted and no patient required withdrawal from the study. The results demonstrate that oral elgodipine is a potent anti-ischaemic agent. An improvement in the echocardiographic parameters of left ventricular systolic and diastolic function was also seen.
Senior R, Buchner-Moell D, Raftery E, et al., 1993, Potent hemodynamic effects of bimakalim, a new potassium channel opener, in humans., J Cardiovasc Pharmacol, Vol: 22, Pages: 717-721, ISSN: 0160-2446
The cardiac hemodynamic effects of bimakalim, a new potassium channel opener, were evaluated in 12 normal volunteers by echocardiography (ECHO)/Doppler in a placebo-controlled, randomized double-blind, cross-over, dose-ranging study. A single oral dose (0.25-1 mg) was given at weekly intervals. Hemodynamic measurements were made at 0, 90, 120, and 240 min after drug intake and ECHO/Doppler was performed at 0 and 90 min. Reproducibility of the ECHO/Doppler study was assessed by comparing predose baseline values of the four different phases of treatment (placebo and 0.25, 0.5, and 1 mg) by analysis of variance (ANOVA), which showed no significant differences for left ventricular ejection fraction (LVEF). Doppler-derived stroke volume (SV), total peripheral resistance (TPR), and peak mitral early to late velocity ratio (PEV/PAV). ANOVA showed significant increases in LVEF (p = 0.0003) and SV (p = 0.03), however, and decreases in TPR (p = 0.002) and PEV/PAV (p = 0.005) after bimakalim treatment. Heart rate (HR) showed a dose-dependent increase, but systolic and diastolic blood pressure (SBP, DBP) did not change with bimakalim. Despite vasodilatory headaches, none of the volunteers discontinued the study. Bimakalim appears to be a potent vasodilating drug that may have an important role in management of patients with compromised LV function.
Senior R, Bhattacharya S, Manspeaker P, et al., 1993, 99mTc-antimyosin antibody imaging for the detection of acute myocardial infarction in human beings., Am Heart J, Vol: 126, Pages: 536-542, ISSN: 0002-8703
111In-antimyosin imaging is a highly sensitive and specific technique for the detection of myocardial necrosis. Two new methods of labeling antimyosin with 99mTc have been developed, and were compared with the standard 111In-antimyosin imaging technique in 29 patients with acute myocardial infarction. Fourteen patients (group I) received directly labeled 99mTc-antimyosin, and 15 (group II) were given RP-1 conjugated 99mTc-antimyosin. 99mTc-antimyosin imaging was performed at 6, 12, and 24 hours, and 111In-antimyosin imaging was done at 24 and 48 hours following injection. The images were interpreted by three blinded observers. In group I, 99mTc-antimyosin uptake could be detected in 3, 6, and 12 cases at 6, 12, and 24 hours, respectively, compared with only 8 cases at 24 hours with 111In-antimyosin. At 48 hours all patients showed 111In-antimyosin uptake. In group II, 99mTc-antimyosin uptake could be detected in 2, 3, and 6 cases at 6, 12, and 24 hours, respectively, compared with 8 and 12 cases at 24 and 48 hours, respectively, with 111In-antimyosin. Gated blood pool studies could be obtained in all patients following 99mTc-antimyosin injection and could be used to identify regional wall motion abnormalities. The plasma half-lives of 99mTc-antimyosin in group I and group II were 2.67 +/- 0.3 hours and 4.23 +/- 0.3 hours, respectively, and the plasma half-life of 111In-antimyosin was 6.3 +/- 0.4 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
Senior R, Raftery EB, 1993, Infection of left ventricular thrombus in a patient with silent myocardial infarction--a unique complication., Eur Heart J, Vol: 14, Pages: 997-998, ISSN: 0195-668X
A 72-year-old male was admitted to hospital with exertional dyspnoea of recent onset. Echocardiography showed a left ventricle which was severely hypokinetic on the anteroseptal and anterior wall with an akinetic inferior wall and apex. A string of globular masses was seen to be floating in the left ventricle, attached to the septum near the apex. Coronary arteriography showed severe two-vessel disease. Urgent surgery revealed degenerated thrombus in the left ventricle containing green pus. The infected thrombus was attached to an area of septal infarction. The pus-filled thrombus was removed and by-pass grafting was effected. No infective organism was identified.
Senior R, Imbs JL, Bory M, et al., 1993, Indapamide reduces hypertensive left ventricular hypertrophy: an international multicenter study., J Cardiovasc Pharmacol, Vol: 22 Suppl 6, Pages: S106-S110, ISSN: 0160-2446
The effect of 6 months of treatment with indapamide (IND, 2.5 mg/day) on regression of left ventricular hypertrophy (LVH), an independent predictor of poor prognosis in hypertension, was compared by echocardiography to that of nifedipine (NFD, 40 mg/day), enalapril (ENL, 20 mg/day), atenolol (ATL, 100 mg/day), and hydrochlorothiazide (HCTZ, 25 mg/day) in four parallel double-blind studies in 151 hypertensive patients with a diastolic blood pressure between 95 and 120 mm Hg and a raised left ventricular mass index (LVMI) (mg/m2) (Devereux). Patients were randomized to IND or comparator following a 2-week washout (1 month in the IND vs. ATL study). Respective baseline and 6-month LVMI values (mg/m2) were: IND (n = 20) vs. HCTZ (n = 20): 151.4 +/- 6.3 and 125.70 +/- 4.6 (p < 0.001) vs. 141.3 +/- 6.6 and 135.6 +/- 8.3 (p = N.S.); IND (n = 22) vs NFD (n = 19): 144.1 +/- 5.3 and 125.1 +/- 4.3 (p < 0.001) vs. 170.4 +/- 6.6 and 148.2 +/- 6.2 (p < 0.001); IND (n = 9) vs. ENL (n = 9): 155.1 +/- 6.3 and 143.4 +/- 5.2 (p < 0.001) vs. 142.0 +/- 6.7 and 130.0 +/- 5.9 (p < 0.001); IND (n = 17) vs. ATL (n = 12): 146.2 +/- 5.1 and 130.8 +/- 6.5 (p < 0.001) vs. 156.7 +/- 8.4 and 142.9 +/- 10.3 (p < 0.01). All drugs significantly reduced diastolic blood pressure, and all except HCTZ induced a significant and similar reduction in left ventricular mass.
Senior R, Cowell R, Thomas P, et al., 1992, Right atrial thrombus migration during echocardiography: a case for urgent intervention., Eur Heart J, Vol: 13, Pages: 1724-1725, ISSN: 0195-668X
A 65-year-old woman presented with increasing shortness of breath, chest pain and ST-T wave abnormalities on the electrocardiogram suggestive of unstable angina. Cross-sectional echocardiography performed to assess wall-motion abnormality and left ventricular function revealed a pedunculated right atrial thrombus prolapsing into the right ventricle which suddenly dislodged and migrated into the pulmonary circulation during the examination. A diagnosis of recurrent pulmonary thromboembolism was made, necessitating urgent pulmonary angiography with infusion of streptokinase. The patient made an uneventful recovery.
Bhattacharya S, Senior R, Liu XJ, et al., 1992, Quantitative 111In antimyosin antibody imaging to predict the age of myocardial infarction., Int J Card Imaging, Vol: 8, Pages: 103-107, ISSN: 0167-9899
To establish whether quantitative 111In antimyosin uptake can be used to predict infarct age, we studied the heart-lung ratio in 107 images from 90 patients at various intervals following a Q-wave infarction. Imaging was performed 24 hours following 111In antimyosin injection. The HLR was measured as the ratio of the maximum counts in the infarcted myocardium to the adjacent lung background. The ratio ranged from 1.26 to 3.87, and declined with increasing infarct age. Infarcts were classified on the basis of age as type I (less than 3 days old), type II (less than 14 days), and type III (less than 90 days). True positive and false positive rates (TPR and FPR), and test-likelihood ratio calculations were performed for HLR thresholds ranging from 1 to 4, for the three infarct types. A FPR of 0% and likelihood ratio of infinity was obtained at a HLR threshold of 2.3 for type I infarcts (TPR 40.8%); at a HLR threshold of 2 for type II infarcts (TPR 50.6%), and a threshold of 1.8 for type III infarcts (TPR 52.6%). The likelihood of each infarct type can be estimated directly from the HLR for values below the above thresholds. These results show that quantitative 111In-antimyosin imaging may be used to predict infarct age.
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