Paul K. Blanksma

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.

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.

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.

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.

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.

Assessment of quantitative hypertrophy scores in hypertrophic cardiomyopathy: Magnetic resonance imaging versus echocardiography

To compare the diagnostic value of spin-echo magnetic resonance (MR) imaging and transthoracic echocardiography in quantitative assessment of the extent of hypertrophy in patients with hypertrophic cardiomyopathy (HCM), we examined 52 consecutive patients with HCM. The Spirito-Maron and Wigle hypertrophy scores were calculated with wall thickness measurements obtained by both imaging modalities. MR imaging yielded complete assessment of anatomic features and allowed calculation of hypertrophy scores in 49 patients (94%). Adequate echocardiograms were obtained in 33 patients (63%) and correlated well with MR imaging for wall thickness measurements and for determination of the two hypertrophy scores (both r> 0.9). MR imaging provided additional information not available by echocardiography in 16 patients (31%). We conclude that the Spirito-Maron and Wigle hypertrophy scores correlated well between echocardiography and MR imaging. Because echocardiography was of insufficient quality for calculating adequate hypertrophy scores in 19 (37%) patients, MR imaging provided the most comprehensive diagnostic information in patients with HCM.

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.

Automated ejection fraction determination from gated myocardial FDG-PET data

BackgroundThe aim of this study was to determine the potential of the automated calculation of the left ventricular ejection fraction from gated myocardial positron emission tomography (PET) scans.MethodsWe retrospectively analyzed the data of 20 patients who underwent both gated fluorine 18 deoxyglucose (FDG)-PET and equilibrium radionuclide angiography (ERNA). Gated PET data were analyzed by 2 independent programs (ie, quantitative gated single photon emission computed tomography [QGS]) originally developed for gated single photon emission computed tomography studies and functional polarmap (FPM) originally developed for the analysis of (functional) dynamic PET studies. ERNA data were used as the gold standard.ResultsBoth QGS and FPM left ventricular ejection fraction results correlated highly with ERNA (y=0.90 × x-5.9, r =0.86, P <.0001; y =0.80 × x+3.3, r = 0.84, P < .0001, respectively). The correlation between FPM and QGS left ventricular ejection fraction results was even higher (y=0.89 × x+8.6, r=0.97, P<.0001). Bland-Altman plots showed systematic differences in the left ventricular ejection fraction of −9.6%±7.5% (QGS vs ERNA), −3.8%±7.8% (FPM vs ERNA), and −5.8%±3.5% (QGS vs FPM). Further comparison of the left ventricular volumes revealed systematic difference between QGS and FPM. Our results indicate that the correlation between the different left ventricular ejection fractions shows little sensitivity to errors in the left ventricular volumes; however, the exact relationship is influenced by these errors.ConclusionIt is concluded that the automated determination of the left ventricular ejection fraction from gated PET data has significant potential; its results are highly and significantly correlated with ERNA. However, the methods presented here require additional calibration before final accuracy and clinical applicability can be determined.

Coronary vasomotion in patients with syndrome X : Evaluation with positron emission tomography and parametric myocardial perfusion imaging

The aim of this study was to elucidate further the causative mechanism of abnormal coronary vasomotion in patients with syndrome X. In patients with syndrome X, defined as angina pectoris and documented myocardial ischaemia during stress testing with normal findings at coronary angiography, abnormal coronary vasomotion of either the micro- or the macrocirculation has been suggested as the causative mechanism. Accordingly, we evaluated endothelial function, vasodilator reserve, and perfusion heterogeneity in these patients. Twenty-five patients with syndrome X (definitely normal coronary arteriogram, group A), 15 patients with minimal coronary artery disease (group B) and 21 healthy volunteers underwent [13N]ammonia positron emission tomography at rest, during cold pressor stimulation (endothelial function) and during dipyridamole stress testing (vasodilator reserve). Heterogeneity of myocardial perfusion was analysed by parametric polar mapping using a 480-segment model. In both patient groups, resting perfusion was increased compared to the normal subjects: group A, 127±31 ml·min−1·100 g−1; group B, 124±30 ml·min−1·100 g−1 normal subjects, 105±21 ml·min−1·100 g−1 (groups A and B vs normals,P<0.05). These differences were abolished after correction for rate-pressure product. During cold pressor stimulation, the perfusion responses (ratio of cold pressor perfusion to resting perfusion) were similar among the patients and the control subjects (group A, 1.20±0.23; group B, 1.24±0.22; normal subjects, 1.23±0.14). Likewise, during dipyridamole stress testing, perfusion responses were similar among the three groups (group A, 2.71±0.67; group B, 2.77±1.29; normal subjects, 2.91±1.04). In group A the heterogeneity of resting perfusion, expressed as coefficient of variation, was significantly different from the volunteers (20.1±4.5 vs 17.0±3.0,P<0.05). In group B (coefficient of variation 19.4±3.9) the difference from normal volunteers was not significant. In this study, patients with syndrome X and patients with minimal coronary artery disease showed normal perfusion responses during cold pressor stimulation and dipyridamole stress testing. Our findings therefore suggest that endothelial dysfunction and impaired vasodilator reserve are of no major pathophysiological relevance in patients with syndrome X. Rather, other mechanisms such as increased sympathetic tone and focal release of vasoactive substances may play a role in the pathogenesis of syndrome X.

Normal values and reproducibility of left ventricular filling parameters by radionuclide angiography

Background. In physiologic situations age, heart rate (HR) and left ventricular ejection fraction (EF) may influence left ventricular filling rate. In this study, we determined normal values for radionuclide angiography (RNA) derived diastolic filling parameters, the correlations with age, HR and EF and their reproducibility. Methods. The study was performed in 20 patients, 40–76 years old (mean 57), with normal findings at coronary angiography and left ventriculography. The first RNA was performed at rest (RNA1). Then, five minutes bicycle ergometry was performed and the patients were allowed five minutes rest before RNA was repeated (RNA2). From the left ventricular time activity curve we determined peak filling rate (PFR), time to peak filling rate (TPFR) and atrial contribution (AC) to ventricular filling. Results. Values for PFR1 were 2.2 ± 0.6 EDV/sec (PFR2 2.4 ± 0.7 EDV/sec, r = 0.82), for TPFR1 198 ± 22 msec (TPFR2 203 ± 24 msec, r = 0.45) and for AC1 31 ± 11% (AC2 31 ± 10%, r = 0.72). The correlations of PFR and TPFR with age were statistically significant (respectively r = - 0.68 and r = 0.48, P < 0.05). PFR was also influenced by HR and EF (resp. r = 0.51 and r = 0.50, P < 0.05). TPFR however was not influenced by HR and EF, whereas AC was positively correlated with HR (r = 0.79, P < 0.01). Conclusions. Radionuclide angiography is a reliable and reproducible method to assess parameters of diastolic left ventricular filling in individual patients. It may therefore be used to serially follow diastolic function. When used for interindividual comparison the dependency of RNA derived left ventricular filling parameters on age, HR and EF should however be considered.