Left ventricular beat-to-beat performance in atrial fibrillation: contribution of Frank-Starling mechanism after short rather than long RR intervals.

OBJECTIVES: This study sought to evaluate control mechanism of the varying left ventricular performance in atrial fibrillation. BACKGROUND: Atrial fibrillation is characterized by a randomly irregular ventricular response, resulting in continuous variation in left ventricular beat-to-beat mechanical behavior and hemodynamic variables. METHODS: Fourteen patients with chronic nonvalvular atrial fibrillation were studied, using a nonimaging computerized nuclear probe linked to a personal computer. Left ventricular ejection fraction, end-diastolic and end-systolic volume counts, stroke volume counts and filling time were calculated on a beat-to-beat basis during 500 consecutive RR intervals. Multiple regression analysis was used to assess how ejection fraction was predicted by these variables. RESULTS: The preceding RR interval and end-diastolic volume showed a positive relation, and prepreceding interval and end-systolic volume an inverse relation, with ejection fraction (all p < 0.001). Sensitivity analysis suggested that the preceding interval and the end-diastolic volume were equally important in predicting ejection fraction. There was a relatively strong interaction between the preceding interval and end-diastolic volume, indicating that the influence of the end-diastolic volume on ejection fraction was diminished after long intervals. A second interaction showed that the effect of end-diastolic volume on ejection fraction was attenuated after short prepreceding cycles. CONCLUSIONS: Cycle length-dependent contractile mechanisms, including postextrasystolic potentiation and mechanical restitution, determine the varying left ventricular systolic performance during atrial fibrillation over the entire range of intervals. Beat-to-beat changes in preload, consistent with the Frank-Starling mechanism, also play a role, but their influence is diminished after long preceding and short prepreceding intervals.

Regional myocardial blood flow reserve impairment and metabolic changes suggesting myocardial ischemia in patients with idiopathic dilated cardiomyopathy.

OBJECTIVES: We performed positron emission tomography (PET) to evaluate myocardial ischemia in patients with idiopathic dilated cardiomyopathy (IDC). BACKGROUND: Patients with IDC have anatomically normal coronary arteries, and it has been assumed that myocardial ischemia does not occur. METHODS: We studied 22 patients with IDC and 22 control subjects using PET with nitrogen-13 ammonia to measure myocardial blood flow (MBF) at rest and during dipyridamole-induced hyperemia. To investigate glucose metabolism, fluorine-18 deoxyglucose (18FDG) was used. For imaging of oxygen consumption, carbon-11 acetate clearance rate constants (k(mono)) were assessed at rest and during submaximal dobutamine infusion (20 microg/kg body weight per min). RESULTS: Global MBF reserve (dipyridamole-induced) was impaired in patients with IDC versus control subjects (1.7 +/- 0.21 vs. 2.7 +/- 0.10, p < 0.05). In patients with IDC, MBF reserve correlated with left ventricular (LV) systolic wall stress (r = -0.61, p = 0.01). Furthermore, in 16 of 22 patients with IDC (derived by dipyridamole perfusion) mismatch (decreased flow/increased 18FDG uptake) was observed in 17 +/- 8% of the myocardium. The extent of mismatch correlated with LV systolic wall stress (r = 0.64, p = 0.02). The MBF reserve was lower in the mismatch regions than in the normal regions (1.58 +/- 0.13 vs. 1.90 +/- 0.18, p < 0.05). During dobutamine infusion k(mono) was higher in the mismatch regions than in the normal regions (0.104 +/- 0.017 vs. 0.087 +/- 0.016 min(-1), p < 0.05). In the mismatch regions 18FDG uptake correlated negatively with rest k(mono) (r = -0.65, p < 0.05), suggesting a switch from aerobic to anaerobic metabolism. CONCLUSIONS: Patients with IDC have a decreased MBF reserve. In addition, low MBF reserve was paralleled by high LV systolic wall stress. These global observations were associated with substantial myocardial mismatch areas showing the lowest MBF reserves. In geographically identical regions an abnormal oxygen consumption pattern was seen together with a switch from aerobic to anaerobic metabolism. These data support the notion that regional myocardial ischemia plays a role in IDC.

No difference in cardiac event-free survival between positron emission tomography-guided and single-photon emission computed tomography-guided patient management: a prospective, randomized comparison of patients with suspicion of jeopardized myocardium.

OBJECTIVES: We sought to prospectively compare nitrogen-13 (13N)-ammonia/18fluorodeoxyglucose (18FDG) positron emission tomography (PET)-guided management with stress/rest technetium-99m (99mTc)-sestamibi single-photon emission computed tomography (SPECT)-guided management. BACKGROUND: Patients with evidence of jeopardized (i.e., ischemic or viable) myocardium may benefit from revascularization, whereas patients without it should be treated with drugs. Both PET and SPECT imaging have been proven to delineate jeopardized myocardium. When patient management is based on identification of jeopardized myocardium, it is unknown which technique is most accurate for long-term prognosis. METHODS: In a clinical setting, 103 patients considered for revascularization with left ventricular wall motion abnormalities and suspicion of jeopardized myocardium underwent both PET and SPECT imaging. The imaging results were used in a randomized fashion to determine management (percutaneous transluminal coronary angioplasty [PTCA], coronary artery bypass graft surgery [CABG] or drug treatment). Follow-up for cardiac events (cardiac death, myocardial infarction and revascularization) was recorded for 28 +/- 1 months. The study was designed to have a power of 80% to detect a 20% difference in the event rate between PET- and SPECT-based management. RESULTS: Management decisions in 49 patients randomized to PET (12 who had PTCA, 14 CABG and 23 drug therapy) were comparable with 54 patients randomized to SPECT (15 who had PTCA, 13 CABG and 26 drug therapy). In terms of cardiac event-free survival, no differences between PET and SPECT were observed (11 vs. 13 cardiac events for PET and SPECT, respectively; p = NS by the Kaplan-Meier statistic). CONCLUSIONS: No difference in patient management or cardiac event-free survival was demonstrated between management based on 13N-ammonia/18FDG PET and that based on stress/rest 99mTc-sestamibi SPECT imaging. Both techniques may be used for management of patients considered for revascularization with suspicion of jeopardized myocardium.

Current views on neurostimulation in the treatment of cardiac ischemic syndromes.

Most clinicians are still unacquainted with the beneficial effects of neurostimulation as an additional therapeutic strategy for severe angina pectoris. Patients with therapeutically refractory angina pectoris suffer from chest discomfort during minimal exercise, despite maximal tolerated antianginal drug therapy (at least 2 out of a beta-blocker, calcium-antagonist or long-acting nitrate). In these patients, revascularization procedures, such as a percutaneous transluminal coronary angioplasty or coronary artery bypass surgery, are often technically impossible because of diffuse coronary artery disease or should be withheld as a consequence of absolute contraindications such as severe left ventricular dysfunction. All patients have inoperable multivessel disease, experienced one or more myocardial infarctions, and were treated by earlier invasive interventions. This group of patients are severely physically and psychologically disabled by their intractable angina pectoris. Available published data and the neurostimulation experience of the authors are reviewed in relation to the treatment of cardiac ischemic syndromes. We conclude that neurostimulation is an effective therapeutic adjuvant for patients with severe angina pectoris unresponsive to standard treatment. This treatment modality appears to be safe, and a promising tool for other ischemic cardiac syndromes.

Posterolateral defect of the normal human heart investigated with nitrogen-13-ammonia and dynamic PET.

UNLABELLED: The posterolateral defect is a common artifact seen when static 13N-ammonia imaging with PET is used to assess myocardial perfusion. The aim of this study was to compare dynamic and static. 13N-ammonia PET and to obtain more insight into the cause of the posterolateral defect. METHODS: Dynamic 13N-ammonia PET was performed in 19 healthy nonsmoking volunteers at rest. Perfusion was assessed in the early phase of the study using a curve fit method over the first 90 sec. Nitrogen-13 accumulation (static PET) was assessed 4 to 8 min after injection. Each study was normalized to a mean of 100. The average distribution of normalized perfusion and activity was calculated in 24 segments. Heterogeneity of both activity and perfusion distribution were assessed and the activity distribution was compared with perfusion distribution. RESULTS: Perfusion distribution was homogeneous, with the exception of the inferior and apical regions. Activity distribution was inhomogeneous, with a lower activity in the posterolateral and apical regions. In the whole left ventricle, significant differences in distribution were found between static and dynamic imaging. CONCLUSION: Perfusion distribution was significantly different on dynamic images compared to static images. The posterolateral defect was not found on dynamic images. The posterolateral defect and other inhomogeneities in activity distribution are caused by tracer-dependent features, probably a redistribution of metabolites of 13N-ammonia.

Quantitative myocardial mapping of perfusion and metabolism using parametric polar map displays in cardiac PET.

UNLABELLED: Most efficacy studies of cardiac PET in demonstrating myocardial ischemia and viability have been performed using one or more transversal static images of the heart. In contrast, in this paper we describe a method of functional imaging of the complete left ventricular myocardium for perfusion with nitrogen-13-ammonia, both at rest and during a dipyridamol stress test, and of glucose metabolism with 18F-fluorodeoxyglucose (18FDG). METHODS: This was performed by using the data of each of 48 radial segments of 10 short-axis images as tissue data and LV cavity data of three basal planes as blood pool data. The study describes the results of 19 normal volunteers and 36 patients with coronary artery disease. From the data of the normal volunteers a 95% normal confidence interval was calculated for each imaging modality. These intervals were then used to describe the patient data as normal, ischemic or infarcted. RESULTS: The results of analysis of the parametric images was compared with the results of static analysis of the same patient data and found to be less dependant on the detection threshold used. CONCLUSION: The described method enables the routine application of functional PET imaging of the total myocardium by the semi-automatic construction of parametric flow and metabolism polar maps. It thus provides an increased performance in the diagnosis, quantification and localization of myocardial ischemia and viability over conventional PET imaging.

A mathematical model for the heterogeneity of myocardial perfusion using nitrogen-13-ammonia.

UNLABELLED: Heterogeneity of left ventricular myocardial perfusion is an important clinical characteristic. Different aspects of this heterogeneity were analyzed. METHODS: The coefficient of variation (v), characterizing heterogeneity, was modeled as a function of the number of segments (n), characterizing spatial resolution of the measurement, using two independent pairs of mutually dependent parameters: the first pair describes v as a power function of n, and the second pair adds a correction for n small. n was varied by joining equal numbers of neighboring segments. Local similarity of the perfusion was characterized by the correlation between the perfusions of neighboring segments. Genesis of the perfusion distribution was modeled by repeated asymmetric subdivision of the perfusion into a volume among two equal subvolumes. These analyses were applied to study the differences between 16 syndrome X patients and 16 age- and sex-matched healthy volunteers using 13N-ammonia parametric PET perfusion data with a spatial resolution of 480 segments. RESULTS: The heterogeneity of patients is higher for the whole range of spatial resolutions considered (2 < or = n < or = 480; for n = 480, v = 0.22 +/- 0.03 and 0.18 +/- 0.02; p < 0.005). This is because the first pair of parameters differs between patients and volunteers (p < 0.005), whereas the second pair does not (p > 0.1). For both groups of subjects there is a significant positive local correlation for distances up to 30 segments. This correlation is a formal description of the patchy nature of the perfusion distribution. CONCLUSION: When comparing values of v, these should be based on the same value of n. The model makes it possible to calculate v for all values of n < or = 480. Mean perfusion together with the two pairs of parameters are necessary and sufficient to describe all aspects of the perfusion distribution. For n small, heterogeneity estimation is less reliable. Patients have a higher heterogeneity because their perfusion distribution is more asymmetrical from the third to the seventh generation of subdivision (8 < or = n < or = 128). Therefore, a spatial resolution of n > or = 128 is recommended for parametric imaging of perfusion with PET. Patients have only a very slightly more patchy distribution than volunteers. The differences in perfusion between areas with low perfusion and areas with high perfusion is larger in patients.

Comparison of myocardial uptake of fluorine-18-fluorodeoxyglucose imaged with PET and SPECT in dyssynergic myocardium.

UNLABELLED: PET with 18F-fluorodeoxyglucose (FDG) can detect viable myocardium and predict functional recovery after revascularization. The use of PET for clinical routine, however, is limited. Recently, imaging FDG with SPECT was proposed. The aim of this study was to compare the diagnostic value of FDG-PET and FDG-SPECT in the detection of viable myocardium in segments with abnormal wall motion. METHODS: Twenty patients with previous myocardial infarction were studied. All underwent FDG-PET and FDG-SPECT during hyperinsulinemic glucose clamping. Regional perfusion was assessed with 13N-ammonia PET and early resting 201TI- SPECT. Regional wall motion was assessed with two-dimensional echocardiography. The agreement between FDG/13N-ammonia PET and FDG/201TISPECT to detect viability in dyssynergic myocardium was 76%. On a patient basis, PET and SPECT yielded comparable results in 17 of 20 patients. In a subgroup of patients with LVEF < or = 35% (n = 12), all PET and SPECT viability data were identical. CONCLUSION: This study shows a good correlation between the detection of viability in dyssynergic myocardium with FDG/13N-ammonia PET and FDG/201TI SPECT, both on a segmental and patient basis.

Parametric polar maps of regional myocardial beta-adrenoceptor density.

UNLABELLED: Quantification of myocardial beta-adrenoceptor density (Bmax) is of interest in cardiac diseases in which altered function of the sympathetic nervous system is thought to play a pathophysiological role. PET provides an unrivaled means of taking regional measurements of cardiac microcirculatory function, tissue metabolism and autonomic nervous system activity. Measurements in small regional areas may be biased because of increased noise levels. This study examined the parametric polar map approach for the regional quantification of Bmax. METHODS: Dynamic PET with parametric polar map imaging was performed in 10 healthy volunteers and 4 patients with hypertrophic cardiomyopathy using (S)-[11C]-(4-(3-tertiarybutylamino-2-hydroxypropoxy)-benzidimaz ole-2)-on hydrochloride (CGP)-12177 and a double-injection protocol. Time-activity curves were corrected for partial volume, spill-over and wall motion effects. The mean Bmax of the left ventricle was calculated in two ways. First, the average time-activity curve of all segments, having the highest achievable signal-to-noise ratio, was used to calculate Bmax(mTAC) (the myocardial beta-adrenoceptor density of the left ventricle calculated using the average time-activity curve). The bias in Bmax(mTAC) introduced by noise is minimal. Second, an estimate of whole-heart receptor density was calculated using the polar map method by averaging the values of Bmax obtained for 576 individual segments. In these calculations, three different filters (3 x 5, 3 x 9 and 3 x 13 segments) were used to smooth the time-activity curves before calculating Bmax. Mean values of whole-left-ventricular receptor density obtained by averaging regional values using the different filters (Bmax(PMF1/2/3)) were compared with Bmax(mTAC) to assess bias introduced by the polar map approach. Segments with a calculated Bmax outside the range 0.1-50 pmol/g were considered unreliable and were excluded from the analysis. RESULTS: The differences between the two methods of calculating Bmax were small (7.8%, 4.8% and 3.2%, with the three filters, respectively). Reliable results were obtained in >95% of the segments and in 9 volunteers and all 4 patients. CONCLUSION: When using PET for the quantification of beta-adrenoceptor density, the regional variation in Bmax can be reliably assessed using the parametric polar map approach.

Effect of spinal cord stimulation on myocardial blood flow assessed by positron emission tomography in patients with refractory angina pectoris.

Spinal cord stimulation in angina pectoris increases exercise capacity and reduces both anginal attacks and ischemic electrocardiographic signs. This suggests an anti-ischemic action, perhaps through changes in myocardial blood flow. In 9 patients, regional myocardial blood flow was studied with positron emission tomography before and after 6 weeks of spinal cord stimulation, both at rest and during a dipyridamole stress test. Frequency of anginal attacks and consumption of short-acting nitrates were assessed by patient diaries. Exercise duration and time to angina were measured with treadmill exercise tests. After 6 weeks of stimulation, both frequency of daily anginal attacks and nitrogen consumption decreased (3.7 +/- 1.7 vs 1.4 +/- 1.0 [p <0.01] and 2.8 +/- 2.2 vs 1.1 +/- 1.2 tablets [p = 0.01], respectively); exercise duration and time to angina increased (358 +/- 165 vs 493 +/- 225 seconds [p <0.01] and 215 +/- 115 vs 349 +/- 213 seconds [p = 0.02], respectively); and ST-segment depression during dipyridamole stress testing was reduced (0.17 [0 to 0.5] mV vs 0.09 [0 to 0.2] mV, p = 0.04) (all data mean +/- SD). Total resting blood flow remained unchanged (115 +/- 29 vs 127 +/- 31 ml/min/100 g, p = 0.31), but flow reserve decreased (146 +/- 43% vs 122 +/- 39%, p = 0.04). The coefficient of variation of flow, representing flow heterogeneity, decreased after treatment, both at rest (20.1 +/- 3.8% vs 17.4 +/- 2.6%, p = 0.04) and after dipyridamole stress (26.2 +/- 4.4% vs 22.9 +/- 5.5%, p = 0.02). Thus, spinal cord stimulation is clinically effective due to homogenization of myocardial blood flow. Since flow reserve decreases despite clinical improvement, the dipyridamole effect may be blunted by spinal cord stimulation.

Comparison between positron emission tomography myocardial perfusion imaging and intracoronary Doppler flow velocity measurements at rest and during cold pressor testing in angiographically normal coronary arteries in patients with one-vessel coronary artery disease.

With use of invasive methods, coronary endothelial function is generally studied by examining the response of epicardial coronary arteries to intracoronary administered acetylcholine or to cold pressor testing. Because invasive methods have substantial inherent limitations, studies should attempt to evaluate coronary endothelial function noninvasively. This study examines a noninvasive technique for endothelium-related coronary stress testing. In myocardial regions supplied by nonstenotic coronary arteries, we compared positron emission tomography (PET) myocardial perfusion imaging with intracoronary Doppler flow velocity measurements during endothelium-related stress testing. PET perfusion was examined at rest and during cold pressor testing in 10 patients with 1-vessel coronary artery disease. In nonstenotic coronary arteries, flow velocity measurements were obtained at rest, during cold pressor testing, and during intracoronary administered acetylcholine. Perfusion and flow velocity responses and stress/rest ratios were compared between the techniques during the various circumstances. Positive correlations were found between: (1) cold pressor Doppler flow velocity responses and acetylcholine Doppler flow velocity responses (r = 0.84, SEE = 0.19, p = 0.003); (2) cold pressor PET perfusion responses and cold pressor Doppler flow velocity responses (r = 0.70, SEE = 0.17, p = 0.02); and (3) cold pressor PET perfusion responses and acetylcholine Doppler flow velocity responses (r = 0.62, SEE = 0.19, p = 0.05). These results suggest that in angiographically normal coronary arteries, both the flow velocity and the perfusion responses during cold pressor testing may be related to the response to acetylcholine.

Categorization of abnormal left ventricular function: comparison between radionuclide angiographic and echocardiographic technique in postinfarction patients.

In postinfarction patients, only biplane echocardiographic evaluation of left ventricular ejection fraction (EF) accurately predicts radionuclide EF > or <0.35, 0.40, and 0.45. A wall motion scoring system that does not account for hyperkinesia of healthy myocardium may be used to discriminate between radionuclide EF > or <0.40 or 0.45, but lacks accuracy for 0.35.

Time course of hemodynamic changes and improvement of exercise tolerance after cardioversion of chronic atrial fibrillation unassociated with cardiac valve disease.

This study prospectively assessed the time course, magnitude and mechanism of the hemodynamic changes after restoration of sinus rhythm in patients with chronic atrial fibrillation (AF) unassociated with valvular disease. Severe cardiac dysfunction may occur after chronic supraventricular tachycardia in patients with and without underlying cardiac disease. Improvement may follow abolishment of the arrhythmia or adequate slowing of the ventricular rate. Eight patients were studied with a mean previous duration of AF of 10 +/- 9 months. Ejection fraction, exercise capacity and the atrial contribution to the left ventricular filling (only during sinus rhythm) were studied before cardioversion, after cardioversion and 1 week, 1 month and 6 months thereafter. A significant improvement in ejection fraction from 36 +/- 13 to 53 +/- 8% (p < 0.05) occurred at 1 month after cardioversion. Concomitantly, peak oxygen consumption had increased at 1 month, from 20.1 +/- 7 to 25.2 +/- 6 ml/min/kg (p < 0.05). Thereafter, no further improvement in hemodynamic parameters occurred. The atrial systole improved already at 1 week (from 3 +/- 5 to 16 +/- 11%, p < 0.05) and remained unchanged thereafter. Thus, restoration of sinus rhythm was associated with a delayed improvement in ejection fraction and maximal exercise capacity, preceded by an early restoration of atrial contractility and an acute slowing of the heart rate. The discrepancy in time course of restoration of atrial and ventricular function parameters suggests that an intrinsic left ventricular cardiomyopathy is present in patients with AF.

Imaging of beta-adrenoceptors in the human thorax using (S)-[(11)C]CGP12388 and positron emission tomography.

We report positron emission tomography studies of beta-adrenoceptors in the human thorax with (S)-[(11)C]CGP12388 (4-(3-(2'-[(11)C]-isopropylamino)-2-hydroxypropoxy)-2H-benzimidazol-2-one). Beta-adrenoceptors have previously been quantified using (S)-[(11)C]CGP12177 (4-(3-tert-butylamino-2-hydroxypropoxy)-2H-benzimidazol-2[(11)C]-one), but (S)-[(11)C]CGP12388 is more easily prepared and therefore more suitable in a clinical setting. (S)-[(11)C]CGP12388 was administered to five healthy volunteers on two separate days (control and pindolol block study). Arterial plasma samples were used to determine clearance, metabolites, and protein binding of the radioligand. Heart, lung and spleen showed high uptake of radioactivity, which was strongly suppressed (68-77%) by pindolol. Plasma clearance of (S)-[(11)C]CGP12388 was rapid, binding to plasma proteins was low (53+/-4%), and the radioligand was slowly metabolized. (S)-[(11)C]CGP12388 produces high-quality images of the human thorax. Uptake of (S)-[(11)C]CGP12388 in heart, lung and spleen represents binding to beta-adrenoceptors. (S)-[(11)C]-CGP12388 seems useful for imaging of beta-adrenoceptors in a clinical setting.

Uptake of radioligands by rat heart and lung in vivo: CGP 12177 does and CGP 26505 does not reflect binding to beta-adrenoceptors.

The biodistribution of (-)-4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H-benzimidazol-2-one (CGP12177, a non-selective beta-adrenoceptor antagonist) and 1-[2-(3-carbamoyl-4-hydroxy)-(5-3H-phenoxy)]-2-propanol methanesulfonate, (CGP26505, a beta 1-adrenoceptor antagonist) was studied in rats pretreated with various alpha- and beta-adrenoceptor blocking drugs (5 min before 3H injection, in dosages at which the drugs demonstrated the expected selectivity). Cardiac and pulmonary radioactivity were measured after 10 min, when specific binding was maximal. Uptake of [3H]CGP12177 was linked to binding to beta-adrenoceptors since it was not affected by prazosin or yohimbine, and was equally well inhibited by propranolol, unlabelled CGP12177 and isoprenaline. Moreover, atenolol and CGP20712A inhibited [3H]CGP12177 uptake in heart (predominantly beta 1-adrenoceptors) more potently than ICI 118,551, while in lungs (predominantly beta 2-adrenoceptors) ICI 118,551 was more potent than atenolol or CGP20712A. In contrast, [3H]CGP26505 uptake in the target organs was equally effectively inhibited by propranolol and ICI 118,551, and significantly lowered by alpha-adrenoceptor antagonists. We conclude that [11C]CGP12177, but not [11C]CGP2605 will be suitable for positron emission tomography imaging of beta-adrenoceptors in animals.

Redistribution of myocardial perfusion during permanent dual chamber pacing in symptomatic non-obstructive hypertrophic cardiomyopathy: a quantitative positron emission tomography study.

Dual chamber pacing causes significant symptomatic improvement in many patients with hypertrophic cardiomyopathy. The mechanism behind this beneficial response is not fully understood. Positron emission tomography showed a redistribution of myocardial flow during pacing in a patient with non-obstructive hypertrophic cardiomyopathy. Early septal activation reduced septal fibre strain and blood flow and increased septal perfusion reserve.

Effects of permanent dual chamber pacing on myocardial perfusion in symptomatic hypertrophic cardiomyopathy.

OBJECTIVE: Angina and the presence of myocardial ischaemia are common in hypertrophic cardiomyopathy. Dual chamber pacing results in clinical improvement in these patients. This study evaluates the effects of permanent dual chamber pacing on absolute regional myocardial perfusion and perfusion reserve. SETTING: University hospital. PATIENTS AND DESIGN: Six patients with hypertrophic cardiomyopathy and severe symptoms of angina received a dual chamber pacemaker. Absolute myocardial regional perfusion and perfusion reserve (dipyridamole 0.56 mg/kg) were measured by dynamic positron emission tomography with 13N-ammonia both during sinus rhythm and 3 months after pacemaker insertion. Results were compared with those from 28 healthy volunteers. RESULTS: Pacing resulted in a reduction of anginal complaints and a reduction in intraventricular pressure gradient from 65 (SD 30) mm Hg to 19 (10) mm Hg. During sinus rhythm, baseline perfusion was higher in patients with hypertrophic cardiomyopathy than controls (184 (31) v 106 (26) ml/min/100 g, P < 0.01), and perfusion reserve was lower (1.6 (0.4) v 2.8 (1.0), P < 0.05). During pacing myocardial perfusion decreased to 130 (27) ml/min/100 g (P < 0.05), with variable responses in terms of perfusion reserve. Pacing caused a redistribution of myocardial stress perfusion and perfusion reserve. The coefficient of regional variation of myocardial stress perfusion decreased from 19.7 (7.0)% to 14.6 (3.9)% during pacing (12.9 (3.8)% in controls, P < 0.01). The coefficient of regional variation of perfusion reserve decreased from 16.7 (6.6)% to 11.4 (2.6)% during pacing (9.8 (4.1)% in controls, P < 0.01). CONCLUSIONS: Pacing caused a decrease of resting left ventricular myocardial blood flow and blood flow during pharmacologically induced coronary vasodilatation. Although global perfusion reserve remained unchanged, myocardial perfusion reserve became more homogeneously distributed.

Comparison of 99mTc-sestamibi-18F-fluorodeoxyglucose dual isotope simultaneous acquisition and rest-stress 99mTc-sestamibi single photon emission computed tomography for the assessment of myocardial viability.

Dual isotope simultaneous acquisition single photon emission computed tomography (DISA SPECT) offers the advantage of obtaining information on myocardial perfusion using Tc-sestamibi ( Tc-MIBI) and metabolism using F-fluorodeoxyglucose ( F-FDG) in a single study. The prerequisite is that the Tc-MIBI images are not degraded by scattered 511 keV photons or poor count statistics due to the lower efficiency of the extra high energy (EHE) collimator. Therefore, we compared the registered Tc-MIBI uptake and image quality of DISA and single isotope acquisition. Furthermore, we investigated whether DISA yields additional information for the assessment of myocardial viability in comparison with rest-stress Tc-MIBI. Nineteen patients with known coronary artery disease and irreversible perfusion defects on previous rest-stress MIBI test studies were investigated. After oral glucose loading and simultaneous injection of 600 MBq of Tc-MIBI and 185 MBq of F-FDG at rest, DISA was performed using energy windows of 140 (+/-15%), 170 (+/-20%) and 511 keV (+/-15%). Planar 140 keV images were corrected for scatter by subtraction using the 170 keV window. The single and dual isotope Tc-MIBI images were both displayed in a polar map with 128 segments normalized to maximum counts. F-FDG and Tc-MIBI images were visually scored for a perfusion-metabolism mismatch pattern using nine regions per heart. There was an excellent correlation (r =0.93, P<0.0001) between the Tc-MIBI uptake detected in the single and dual isotope acquisition. The average difference between the dual and single isotope Tc-MIBI uptake was -1.2% (not significantly different from zero) and the coefficient of variation of the difference was 8.7%. Of the 79 regions with irreversible perfusion defects on previous rest-stress Tc-MIBI, six regions in five patients showed a perfusion-metabolism mismatch pattern. We conclude that DISA does not affect the quality of the Tc-MIBI images. Furthermore, F-FDG- Tc-MIBI DISA may show viability in a small but significant (7.6%, P<0.0034) number of regions with irreversible perfusion defects on rest-stress Tc-MIBI.

Angina pectoris refractory for conventional therapy--is neurostimulation a possible alternative treatment?

The treatment of angina pectoris as a symptom of coronary artery disease usually is focused on restoring the balance between oxygen demand and supply of the myocardium by administration of drugs interfering in heart rate, cardiac pre- and afterload, and coronary vascular tone. For nonresponders to drug therapy or for those with jeopardized myocardium, revascularization procedures such as coronary bypass surgery and percutaneous transluminal coronary angioplasty are at hand. However, the atherosclerotic process is not stopped by these therapies and, at longer terms, angina may recur. It is not always possible to revascularize all the patients who do not positively react to medical treatment. Those with angina, not responding to adequate medication and who are not suitable anymore for revascularization, are considered to suffer from refractory angina pectoris. This group of patients has a poor quality of life, for their exercise tolerance is severely afflicted. For these patients, neurostimulation has been described repeatedly as an effective and safe therapy. The mechanism of action of neurostimulation is not completely known, but recent studies suggest an anti-ischemic effect, exerted through changes in myocardial blood flow. As soon as its safety is sufficiently established, it may become a useful alternative in the treatment of refractory angina pectoris.

Numerical simulation of the influence of a left ventricular assist device on the cardiovascular system.

The PUCA (pulsatile catheter) pump is a left ventricular assist device (LVAD) capable of unloading the left ventricle (LV) and improving coronary flow by providing a counterpulsation effect. It consists of an extracorporeal located membrane pump, coupled to a transarterial catheter that enters the body via a superficial artery and ends in the LV. Blood is aspirated from the LV and pumped in the ascending aorta through the same catheter guided by a valve system. Timing and frequency of the PUCA pump influence its efficacy. To study the influence of several pump parameters a numerical model of the device and the circulatory system has been developed. Results of animal experiments were used to validate the model. Optimization studies resulted in a pump configuration with a stroke volume of 50 cc and pump:heart frequency mode of 1:2 that starts ejection at the beginning of diastole.