Sense-B-noise: an enigmatic cause for inappropriate shocks in subcutaneous implantable cardioverter defibrillators.

AIMS: Subcutaneous implantable cardioverter defibrillators (S-ICDs) are well established. However, inappropriate shocks (IAS) remain a source of concern since S-ICDs offer very limited troubleshooting options. In our multicentre case series, we describe several patients who experienced IAS due to a previously unknown S-ICD system issue. METHODS AND RESULTS: We observed six patients suffering from this novel IAS entity. The IAS occurred exclusively in primary or alternate S-ICD sensing vector configuration (therefore called 'Sense-B-noise'). IAS were caused by non-physiologic oversensing episodes characterized by intermittent signal saturation, diminished QRS amplitudes, and disappearance of the artefacts after the IAS. Noise/oversensing could not be provoked by manipulation, X-ray did not show evidence for lead/header issues and impedance measurements were within normal limits. The pooled experience of our centres implies that up to ∼5% of S-ICDs may be affected. The underlying root cause was discussed extensively with the manufacturer but remains unknown and is under further investigation. CONCLUSION: Sense-B-noise is a novel cause for IAS due to non-physiologic signal oversensing, arising from a previously unknown S-ICD system issue. Sense-B-noise may be suspected if episodes of signal saturation in primary or alternate vector configuration are present, oversensing cannot be provoked, and X-ray and electrical measurements appear normal. The issue can be resolved by reprogramming the device to secondary sensing vector.

Prevalence and risk of inappropriate dosing of direct oral anticoagulants in two Swiss atrial fibrillation registries.

BACKGROUND: Direct oral anticoagulants (DOACs) have a favourable risk-benefit profile compared to vitamin K-antagonists (VKAs) in atrial fibrillation (AF). Dosing is based on age, weight and renal function, without need of routine monitoring. METHODS AND RESULTS: In two prospective, multicentre AF cohorts (Swiss-AF, BEAT-AF) patients were stratified as receiving VKAs or adequately-, under- or overdosed DOACs, according to label. Primary outcome was a composite of major adverse clinical events (MACE), defined as cardiovascular death, myocardial infarction (MI), ischaemic stroke and systemic embolism. Secondary outcomes included major bleeding. Adjustment for confounding was performed. Median follow-up was 4 years. Of 3236 patients, 1875 (58%) were on VKAs and 1361 (42%) were on DOACs, of which 1137 (83%) were adequately-, 134 (10%) over- and 90 (7%) under-dosed. Compared to adequately dosed individuals, overdosed patients were more likely to be older and female. Underdosing correlated with concomitant aspirin therapy and coronary artery disease. Both groups had higher CHA2DS2-VASc scores. Patients on overdosed DOACs had higher incidence of MACE (HR 1.75; CI 1.10-2.79; adjusted-HR: 1.22) and major bleeding (HR 1.99; CI 1.14-3.48; adjusted-HR: 1.51). Underdosing was not associated with a higher incidence of MACE (HR 0.94; CI 0.46-1.92; adjusted-HR 0.61) or major bleeding (HR 1.07; CI 0.46-2.46; adjusted-HR 0.82). After adjustment, all CIs crossed 1.0. CONCLUSION: Inappropriate DOAC-dosing was more prevalent in multimorbid patients, but did not correlate with higher risks of adverse events after adjusting for confounders. DOAC prescription should follow label.

Assessment of injury current during leadless pacemaker implantation.

BACKGROUND: Leadless pacemakers are an established treatment option for bradyarrhythmias. Similar to conventional transvenous pacemakers, satisfying pacing values during implantation are targeted for optimal long-term device function. The objective is to investigate the role of a local injury current (IC) in leadless pacemaker implantations. METHOD: The IC, sensing value, capture threshold and impedance were collected in 30 consecutive patients receiving a leadless pacemaker. RESULTS: 39 EGMs were recorded from 30 patients (including 9 device repositions). An IC was detected in 15 cases (38%). At implantation, the presence of an IC was associated with a significantly lower sensing (7.1 ± 3.7 mV vs 12.0 ± 4.0 mV; P = 0.004) and a higher capture threshold (median threshold 1.13 V at 0.24 ms [0.50-2.00] vs 0.50 V at 0.24 ms [0.25-0.75]; P = 0.002) and with a 26 fold higher likelihood of device repositioning compared to the absence of an IC (OR 26.3 [2.79-248], P < 0.001). Patients with an IC in their final implant position had a lower sensing (9.3 ± 4.4 mV vs 13.6 ± 4.7 mV at implantation, P = 0.04), while the initially similar capture threshold was lower after 24 h in the IC group. After 2 weeks, all parameters were similar between the two groups. CONCLUSIONS: Our study shows that an IC can readily be observed during leadless pacemaker implantation associated with a lower sensing and a higher capture threshold at implantation but with similar to even better values during follow-up.

Coronary CT angiography and myocardial perfusion imaging to detect flow-limiting stenoses: a potential gatekeeper for coronary revascularization?

AIMS: To evaluate the diagnostic accuracy of a combined non-invasive assessment of coronary artery disease with coronary CT angiography (CTA) and myocardial perfusion imaging (MPI) for the detection of flow-limiting coronary stenoses and its potential as a gatekeeper for invasive examination and treatment. METHODS AND RESULTS: In 78 patients (mean age 65 +/- 9 years) referred for coronary angiography (CA), additional CTA and MPI (using single-photon emission-computed tomography) were performed and the findings not communicated. Detection of flow-limiting stenoses (justifying revascularization) by the combination of CTA and MPI (CTA/MPI) was compared with the combination of quantitative coronary angiography (QCA) plus MPI (QCA/MPI), which served as standard of reference. The findings of both combinations were related to the treatment strategy (revascularization vs. medical treatment) chosen in the catheterization laboratory based on the CA findings. Sensitivity, specificity, positive and negative predictive value, and accuracy of CTA/MPI for the detection of flow-limiting coronary stenoses were 100% each. More than half of revascularization procedures (21/40, 53%) was performed in patients without flow-limiting stenoses and 76% (47/62) of revascularized vessels were not associated with ischaemia on MPI. CONCLUSION: The combined non-invasive approach CTA/MPI has an excellent accuracy to detect flow-limiting coronary stenoses compared with QCA/MPI and its use as a gatekeeper appears to make a substantial part of revascularization procedures redundant.

Left bundle branch block causes relative but not absolute septal underperfusion during exercise.

AIMS: Left bundle branch block (LBBB) often causes septal perfusion defects in radionuclide myocardial perfusion imaging using exercise (Ex) but rarely using vasodilator stress. We studied whether this is due to an underlying structural disease inherent to spontaneous LBBB or whether it is also found in temporary LBBB induced by right ventricular pacing (PM) indicating a functional rather than a structural alteration. METHODS AND RESULTS: Regional myocardial blood flow (MBF) at rest and at Ex was measured with 15O-H2O and PET in 10 age-matched healthy volunteers (controls), 10 LBBB patients and 10 PM patients with right ventricular pacing off and on (PM off and PM on). Although at Ex septal MBF tended to be higher in LBBB than in controls (3.04 +/- 1.18 vs. 2.27 +/- 0.72 mL/min/g; P = ns), the ratio septal/lateral MBF was 19% lower in LBBB than in controls (P < 0.05). Similarly, switching PM on at Ex decreased the ratio septal/lateral MBF by 17% (P < 0.005). CONCLUSION: The apparent septal perfusion defect in LBBB is mainly due to a relative lateral hyperperfusion rather than to an absolute septal flow decrease. This pattern seems to be reversibly inducible by right ventricular pacing, suggesting a functional rather than a structural alteration.

Functionally relevant coronary artery disease: comparison of 64-section CT angiography with myocardial perfusion SPECT.

PURPOSE: To prospectively determine the accuracy of 64-section computed tomographic (CT) angiography for the depiction of coronary artery disease (CAD) that induces perfusion defects at myocardial perfusion imaging with single photon emission computed tomography (SPECT), by using myocardial perfusion imaging as the reference standard. MATERIALS AND METHODS: All patients gave written informed consent after the study details, including radiation exposure, were explained. The study protocol was approved by the local institutional review board. In patients referred for elective conventional coronary angiography, an additional 64-section CT angiography study and a myocardial perfusion imaging study (1-day adenosine stress-rest protocol) with technetium 99m-tetrofosmin SPECT were performed before conventional angiography. Coronary artery diameter narrowing of 50% or greater at CT angiography was defined as stenosis and was compared with the myocardial perfusion imaging findings. Quantitative coronary angiography served as a reference standard for CT angiography. RESULTS: A total of 1093 coronary segments in 310 coronary arteries in 78 patients (mean age, 65 years +/- 9 [standard deviation]; 35 women) were analyzed. CT angiography revealed stenoses in 137 segments (13%) corresponding to 91 arteries (29%) in 46 patients (59%). SPECT revealed 14 reversible, 13 fixed, and six partially reversible defects in 31 patients (40%). Sensitivity, specificity, and negative and positive predictive values, respectively, of CT angiography in the detection of reversible myocardial perfusion imaging defects were 95%, 53%, 94%, and 58% on a per-patient basis and 95%, 75%, 96%, and 72% on a per-artery basis. Agreement between CT and conventional angiography was very good (96% and kappa = 0.92 for patient-based analysis, 93% and kappa = 0.84 for vessel-based analysis). CONCLUSION: Sixty-four-section CT angiography can help rule out hemodynamically relevant CAD in patients with intermediate to high pretest likelihood, although an abnormal CT angiography study is a poor predictor of ischemia.

Myocardial bridging: depiction rate and morphology at CT coronary angiography--comparison with conventional coronary angiography.

PURPOSE: To prospectively assess the depiction rate and morphologic features of myocardial bridging (MB) of coronary arteries with 64-section computed tomographic (CT) coronary angiography in comparison to conventional coronary angiography. MATERIALS AND METHODS: Patients were simultaneously enrolled in a prospective study comparing CT and conventional coronary angiography, for which ethics committee approval and informed consent were obtained. One hundred patients (38 women, 62 men; mean age, 63.8 years +/- 11.6 [standard deviation]) underwent 64-section CT and conventional coronary angiography. Fifty additional patients (19 women, 31 men; mean age, 59.2 years +/- 13.2) who underwent CT only were also included. CT images were analyzed for the direct signs length, depth, and degree of systolic compression, while conventional angiograms were analyzed for the indirect signs step down-step up phenomenon, milking effect, and systolic compression of the tunneled segment. Statistical analysis was performed with Pearson correlation analysis, the Wilcoxon two-sample test, and Fisher exact tests. RESULTS: MB was detected with CT in 26 (26%) of 100 patients and with conventional angiography in 12 patients (12%). Mean tunneled segment length and depth at CT (n = 150) were 24.3 mm +/- 10.0 and 2.6 mm +/- 0.8, respectively. Systolic compression in the 12 patients was 31.3% +/- 11.0 at CT and 28.2% +/- 10.5 at conventional angiography (r = 0.72, P < .001). With CT, a significant correlation was not found between systolic compression and length (r = 0.16, P = .25, n = 150) but was found with depth (r = 0.65, P < .01, n = 150) of the tunneled segment. In 14 patients in whom MB was found at CT but not at conventional angiography, length, depth, and systolic compression were significantly lower than in patients in whom both modalities depicted the anomaly (P < .001, P < .01, and P < .001, respectively). CONCLUSION: The depiction rate of MB is greater with 64-section CT coronary angiography than with conventional coronary angiography. The degree of systolic compression of MB significantly correlates with tunneled segment depth but not length.

Comparison of diagnostic accuracy of 64-slice computed tomography coronary angiography in patients with low, intermediate, and high cardiovascular risk.

RATIONALE AND OBJECTIVES: The aim of this study was to compare the diagnostic accuracy of 64-slice computed tomographic coronary angiography (CTCA) in groups of patients with low, intermediate, and high risk for coronary artery disease (CAD) events. MATERIALS AND METHODS: The institutional review board approved this study; written informed consent was obtained from all patients. Eighty-eight consecutive patients with suspected CAD (40 women; mean age, 64.3 +/- 9.4 years; range, 39-82) underwent CTCA, calcium scoring, and invasive coronary angiography and were grouped according to their Framingham 10-year risk for hard coronary events into low (<10%), intermediate (10%-20%), and high (>20%) risk categories. Significant stenoses (luminal diameter narrowing > or =50%) were assessed on an intention-to-diagnose-basis; no coronary segment was excluded and nonevaluative segments were rated false positive. To determine differences between groups, Kruskal-Wallis tests were performed for individually determined values of diagnostic performance. RESULTS: Per-patient sensitivity, specificity, negative predictive, and positive predictive values were 90.0%, 79.2%, 95.0%, and 64.3%, respectively, with low (n = 34), 87.5%, 92.3%, 85.7%, and 93.3%, respectively, with intermediate (n = 29), and 100%, 75.0%, 100%, and 89.5%, respectively, with high risk (n = 25), with a trend toward higher positive predictive value (P = .07). Per-segment negative predictive value was lower with high pretest probability (P < .01). Mean calcium-score units were 90, 220, and 312 (P = .23), and the prevalence of CAD was 29.4%, 55.2%, and 68.0% (P < .01) with low, intermediate, and high risk. CONCLUSION: Sensitivity and specificity of CTCA are not influenced by the prevalence of CAD, whereas the negative predictive value is lower and the positive predictive value tends to be higher in patients with a high prevalence of CAD.

Absolute quantification of myocardial blood flow with 13N-ammonia and 3-dimensional PET.

UNLABELLED: The aim of this study was to compare 2-dimensional (2D) and 3-dimensional (3D) dynamic PET for the absolute quantification of myocardial blood flow (MBF) with (13)N-ammonia ((13)N-NH(3)). METHODS: 2D and 3D MBF measurements were collected from 21 patients undergoing cardiac evaluation at rest (n = 14) and during standard adenosine stress (n = 7). A lutetium yttrium oxyorthosilicate-based PET/CT system with retractable septa, enabling the sequential acquisition of 2D and 3D images within the same patient and study, was used. All 2D studies were performed by injecting 700-900 MBq of (13)N-NH(3). For 14 patients, 3D studies were performed with the same injected (13)N-NH(3) dose as that used in 2D studies. For the remaining 7 patients, 3D images were acquired with a lower dose of (13)N-NH(3), that is, 500 MBq. 2D images reconstructed by use of filtered backprojection (FBP) provided the reference standard for MBF measurements. 3D images were reconstructed by use of Fourier rebinning (FORE) with FBP (FORE-FBP), FORE with ordered-subsets expectation maximization (FORE-OSEM), and a reprojection algorithm (RP). RESULTS: Global MBF measurements derived from 3D PET with FORE-FBP (r = 0.97), FORE-OSEM (r = 0.97), and RP (r = 0.97) were well correlated with those derived from 2D FBP (all Ps < 0.0001). The mean +/- SD differences in global MBF measurements between 3D FORE-FBP and 2D FBP and between 3D FORE-OSEM and 2D FBP were 0.01 +/- 0.14 and 0.01 +/- 0.15 mL/min/g, respectively. The mean +/- SD difference in global MBF measurements between 3D RP and 2D FBP was 0.00 +/- 0.16 mL/min/g. The best correlation between 2D PET and 3D PET performed with the lower injected activity was found for the 3D FORE-FBP reconstruction algorithm (r = 0.95, P < 0.001). CONCLUSION: For this scanner type, quantitative measurements of MBF with 3D PET and (13)N-NH(3) were in excellent agreement with those obtained with the 2D technique, even when a lower activity was injected.

Added value of coronary artery calcium score as an adjunct to gated SPECT for the evaluation of coronary artery disease in an intermediate-risk population.

UNLABELLED: The coronary artery calcium (CAC) score is a readily and widely available tool for the noninvasive diagnosis of atherosclerotic coronary artery disease (CAD). The aim of this study was to investigate the added value of the CAC score as an adjunct to gated SPECT for the assessment of CAD in an intermediate-risk population. METHODS: Seventy-seven prospectively recruited patients with intermediate risk (as determined by the Framingham Heart Study 10-y CAD risk score) and referred for coronary angiography because of suspected CAD underwent stress (99m)Tc-tetrofosmin SPECT myocardial perfusion imaging (MPI) and CT CAC scoring within 2 wk before coronary angiography. The sensitivity and specificity of SPECT alone and of the combination of the 2 methods (SPECT plus CAC score) in demonstrating significant CAD (>/=50% stenosis on coronary angiography) were compared. RESULTS: Forty-two (55%) of the 77 patients had CAD on coronary angiography, and 35 (45%) had abnormal SPECT results. The CAC score was significantly higher in subjects with perfusion abnormalities than in those who had normal SPECT results (889 +/- 836 [mean +/- SD] vs. 286 +/- 335; P < 0.0001). Similarly, with rising CAC scores, a larger percentage of patients had CAD. Receiver-operating-characteristic analysis showed that a CAC score of greater than or equal to 709 was the optimal cutoff for detecting CAD missed by SPECT. SPECT alone had a sensitivity and a specificity for the detection of significant CAD of 76% and 91%, respectively. Combining SPECT with the CAC score (at a cutoff of 709) improved the sensitivity of SPECT (from 76% to 86%) for the detection of CAD, in association with a nonsignificant decrease in specificity (from 91% to 86%). CONCLUSION: The CAC score may offer incremental diagnostic information over SPECT data for identifying patients with significant CAD and negative MPI results.

Comparison of 64-slice CT with gated SPECT for evaluation of left ventricular function.

UNLABELLED: Precise and reliable assessment of left ventricular (LV) function and dimensions is prognostically important in cardiac patients. As the integration of SPECT and multislice CT into hybrid scanners will promote the combined use of both techniques in the same patient, a comparison of the 2 methods is pertinent. We aimed at comparing LV dimensions, muscle mass, and function obtained by electrocardiographically gated 64-slice CT versus gated-SPECT. METHODS: Sixty patients (mean age, 64 +/- 8 y) referred for evaluation of coronary artery disease underwent 99mTc-tetrofosmin gated SPECT and 64-slice CT within 4 +/- 2 d. LV ejection fraction (LVEF), end-systolic volume (ESV), and end-diastolic volume (EDV) from CT were compared with SPECT. Additionally, LV muscle mass and quantitative regional wall motion were assessed in 20 patients with both methods. RESULTS: CT was in good agreement with SPECT for quantification of LVEF (r = 0.825), EDV (r = 0.898), and ESV (r = 0.956; all P < 0.0001). LVEF was 59% +/- 13% measured by SPECT and slightly higher but not significantly different by CT (60% +/- 12%; mean difference compared with SPECT, 1.1% +/- 1.7%; P = not significant). A systematic overestimation using CT for EDV (147 +/- 60 mL vs. 113 +/- 52 mL; mean difference, 33.5 +/- 23.1 mL) and ESV (63 +/- 55 mL vs. 53 +/- 49 mL; mean difference, 9.3 +/- 15.9 mL; P < 0.0001) was found compared with SPECT. A good correlation for muscle mass was found between the 2 methods (r = 0.868; P < 0.005). However, muscle mass calculated by SPECT was significantly lower compared with CT (127 +/- 24 g vs. 148 +/- 37 g; mean difference, 23.0 +/- 12.2 g; P < 0.001). The correlation for regional wall motion between the 2 methods was moderate (r = 0.648; P < 0.0001). CONCLUSION: LVEF and LV functional parameters as determined by 64-slice CT agree over a wide range of clinically relevant values with gated SPECT. However, interchangeable use of the 2 techniques should be avoided for LV volumes, muscle mass, and regional wall motion because of variances inherent to the different techniques.

Repeatability of cold pressor test-induced flow increase assessed with H(2)(15)O and PET.

UNLABELLED: The aim of this study was to evaluate the repeatability of endothelium-related myocardial blood flow (MBF) responses to cold pressor testing (CPT) as assessed by PET. METHODS: In 10 age-matched control subjects (26.6 +/- 3.4 y) and 10 tobacco smokers (24.9 +/- 3.3 y) MBF was assessed at rest and after repeated CPT (CPT1 and CPT2, 40 min apart) using PET with H(2)(15)O. CPT was performed by a 2-min immersion of the subject's foot in ice water. MBF values were corrected for cardiac workload (rate.pressure product), and the repeatability of CPT-related MBF values was assessed according to Bland and Altman. RESULTS: Corrected MBF at CPT1 and CPT2 were comparable in control subjects (1.79 +/- 0.37 vs. 1.70 +/- 0.35 mL/min/g; P = not significant [NS]) and in smokers (1.97 +/- 0.42 vs. 1.80 +/- 0.41 mL/min/g; P = NS). Repeatability coefficients in control subjects and smokers were 0.46 mL/min/g (27% of the mean MBF) and 0.51 mL/min/g (27%), respectively. MBF increased significantly after CPT in both groups but tended to be lower in smokers (P = 0.08). CONCLUSION: PET measured MBF combined with CPT is a feasible and repeatable method for the evaluation of endothelium-related changes of MBF.

Thick maximum intensity projections for the assessment of left ventricular function with 64-slice computed tomography.

OBJECTIVE: The objective of this study was to assess the accuracy of thick maximum intensity projections (MIP) from computed tomography (CT) data sets mimicking projection images from biplane ventriculography for evaluation of left ventricular (LV) parameters. MATERIALS AND METHODS: Fifty-eight patients underwent 64-slice CT. Multiphase images were reconstructed in 10% steps of the RR interval. MIP images (70-mm thickness) of the contrast-enhanced LV in fixed 30 degrees right anterior oblique (RAO)/60 degrees left anterior oblique (LAO) and in adapted short-/long-axis planes were reconstructed. LV parameters were calculated using the area-length method formula. Three-dimensional assessment with semiautomated software served as reference standard. RESULTS: Use of thick MIP reconstructions had a high intermethod reliability (86-94%) compared with the 3-dimensional approach. Smaller measurement errors were found for thick MIP reconstructions in adapted short-/long-axis planes. A significant projection error (3.0%, P < 0.001) of thick MIP reconstructions was found using fixed 30 degrees RAO/60 degrees LAO compared with adapted short-/long-axis reconstructions. CONCLUSION: Thick MIP reconstructions with adapted short-/long-axis planes allow an accurate assessment of LV parameters compared with the established 3-dimensional method.

Influence of altitude exposure on coronary flow reserve.

BACKGROUND: Although no data exist on the effect of altitude exposure on coronary flow reserve (CFR), patients with coronary artery disease (CAD) are advised not to exceed moderate altitudes of approximately 2500 m above sea level. We studied the influence of altitude on myocardial blood flow (MBF) in controls and CAD patients. METHODS AND RESULTS: In 10 healthy controls and 8 patients with CAD, MBF was measured by positron emission tomography and 15O-labeled water at rest, during adenosine stress, and after supine bicycle exercise. This protocol was repeated during inhalation of a hypoxic gas mixture corresponding to an altitude of 4500 m (controls) and 2500 m (CAD). Workload was targeted to comparable heart rate-blood pressure products at normoxia and hypoxia. Resting MBF increased significantly in controls at 4500 m (+24%, P<0.01) and in CAD patients at 2500 m (+24%, P<0.05). Altitude had no influence on adenosine-induced hyperemia and CFR. Exercise-induced hyperemia increased significantly in controls (+38%, P<0.01) at 4500 m (despite a reduction in workload, -28%, P<0.0001) but not in CAD patients at 2500 m (moderate decrease in workload, -11%, P<0.05). Exercise-induced reserve was preserved in controls (+10%, P=NS) but decreased in CAD patients (-18%, P<0.005). CONCLUSIONS: At 2500 m altitude, there is a significant decrease in exercise-induced reserve in CAD patients, indicating that compensatory mechanisms might be exhausted even at moderate altitudes, whereas healthy controls have preserved reserve up to 4500 m. Thus, patients with CAD and impaired CFR should be cautious when performing physical exercise even at moderate altitude.

Integrated PET/CT for the assessment of coronary artery disease: a feasibility study.

UNLABELLED: An accurate, noninvasive technique for the diagnosis of coronary artery disease (CAD) should provide complementary information on coronary anatomy and pathophysiologic lesion severity. We present, what is to our knowledge, the first clinical evaluation of integrated PET/CT for combined acquisition of coronary anatomy and perfusion. METHODS: On an integrated PET/CT scanner, contrast-enhanced CT angiography (CTA) and rest/adenosine-stress myocardial perfusion scanning with (13)N-ammonia were performed on 25 patients with CAD documented by coronary angiography. Contrast-enhanced CTA was performed with retrospective electrocardiography gating after injection of 150 mL of intravenous contrast medium. Decisions on whether to treat with revascularization (anatomic lesion plus ischemia) or conservatively (no lesion or no ischemia) based on PET/CT were compared with those based on PET plus coronary angiography. RESULTS: Of the 100 coronary artery segments (left main, left anterior descending, left circumflex, and right in 25 patients), 7 (in 5 patients) were considered impossible to evaluate by CT because of rapid vessel movement but were correctly categorized by PET alone. In the remaining 93 segments, the sensitivity and specificity of PET/CT versus PET plus coronary angiography were 90% and 98%, respectively. Positive and negative predictive values were 82% and 99%, and accuracy was 97%. CONCLUSION: The data of this preliminary study suggest that PET/CT allows accurate noninvasive clinical decision making about CAD. Because of its high negative predictive value, PET/CT may play an important role in noninvasive selection of CAD patients for revascularization. Integration of higher-performance multislice spiral CT scanners into PET/CT hybrids will accelerate the clinical implementation of this technique.

Bicycle exercise stress in PET for assessment of coronary flow reserve: repeatability and comparison with adenosine stress.

UNLABELLED: PET allows absolute measurements of myocardial blood flow (MBF). The aim of the present study was to evaluate the feasibility and repeatability of supine bicycle exercise stress, compared with standard adenosine stress, in PET. METHODS: In 11 healthy volunteers, MBF was assessed at rest, during adenosine-induced (140 microg/kg/min over 7 min) hyperemia, and immediately after supine bicycle exercise (mean workload, 130 W, which is 70% of the predicted value) using PET and (15)O-H(2)O. The assessment was then repeated after 20 min. Coronary flow reserve (CFR) was calculated as hyperemic/resting MBF for adenosine stress and exercise stress. Repeatability was evaluated according to the method of Bland and Altman. RESULTS: No significant differences were found between the paired resting MBF (1.22 +/- 0.16 vs. 1.26 +/- 0.21 mL/min/g; mean difference, 3% +/- 11%) and the hyperemic MBF with adenosine stress (5.13 +/- 0.74 vs. 4.97 +/- 1.05; mean difference, -4% +/- 14%) or exercise stress (2.35 +/- 0.66 vs. 2.25 +/- 0.61; mean difference, -4% +/- 19%). CFR was reproducible with adenosine stress (4.23 +/- 0.62 vs. 4.05 +/- 1.06, P = not statistically significant; mean difference, -5% +/- 19%) and exercise stress (1.91 +/- 0.46 vs. 1.80 +/- 0.44, P = not statistically significant; mean difference, -5% +/- 15%). Repeatability coefficients for MBF were 0.26 (rest), 1.34 (adenosine stress), and 0.82 (exercise stress) mL/min/g. CONCLUSION: Assessment of CFR with (15)O-H(2)O and PET using bicycle exercise in the PET scanner is feasible and at least as repeatable as using adenosine stress.

Gated (99m)Tc-tetrofosmin SPECT for discriminating infarct from artifact in fixed myocardial perfusion defects.

UNLABELLED: Soft-tissue attenuation artifacts generally appear as fixed perfusion-scan defects. Gated (99m)Tc-tetrofosmin SPECT may help differentiate myocardial infarction (MI) from artifacts, as fixed defects with decreased function (wall motion and thickening) probably represent MI, whereas attenuation artifacts represent preserved function. METHODS: Ungated stress and gated rest (99m)Tc-tetrofosmin SPECT was performed on 153 consecutive patients referred for evaluation of coronary artery disease. From stress and summed gated rest images, 107 patients (70%) were identified with isolated fixed defects. The function of the defects was assessed semiquantitatively from gated stress images. The findings were correlated with clinical (history or electrocardiographic Q waves) evidence of MI. RESULTS: Of 62 patients with fixed defects and clinical MI, 60 (97%) had an abnormal defect function. Of 45 patients with no clinical MI, 16 (36%) had decreased function of the defect, possibly indicating silent MI. In 29 of the 45 patients (64%) with no clinical MI, defect function was normal. Because most (90%) fixed defects with normal systolic function occurred in men with inferior fixed defects (87%) or women with anterior fixed defects (3%), these were most likely attenuation artifacts. By reclassifying the condition of patients with fixed defects and normal function as normal, patients with unexplained fixed defects (no clinical MI) decreased from 29% to 10%. CONCLUSION: Gating adds considerable value to (99m)Tc-tetrofosmin SPECT myocardial perfusion imaging in characterizing fixed defects and potentially improves test specificity.

CT attenuation correction for myocardial perfusion quantification using a PET/CT hybrid scanner.

UNLABELLED: In routine PET, a 10- to 20-min transmission scan with a rotating (68)Ge source is commonly obtained for attenuation correction (AC). AC is time-consuming using this procedure and could considerably be shortened by instead using a rapid CT scan. Our aim was to evaluate the feasibility of CT AC in quantitative myocardial perfusion PET using a hybrid PET/CT scanner. METHODS: (13)N-labeled NH(3) and PET were used to measure myocardial blood flow (MBF) (mL/min/g) at rest and during standard adenosine stress. In group 1 (n = 7), CT scans (0.5 s) of the heart area with different tube currents (10, 40, 80, and 120 mA) were compared with a standard (68)Ge transmission (20 min) and with no AC. In group 2 (n = 3), the repeatability of 8 consecutive CT scans at a tube current of 10 mA was assessed. In group 3 (n = 4), emission was preceded and followed by 3 CT scans (10 mA) and 1 (68)Ge scan for each patient. For reconstruction, filtered backprojection (FBP) was compared with iterative reconstruction (IT). RESULTS: For group 1, no significant difference in mean MBF for resting and hyperemic scans was found when emission reconstructed with (68)Ge AC was compared with emission reconstructed with CT AC at any of the different tube currents. Only emission without any correction differed significantly from (68)Ge AC. For group 2, repeated measurements revealed a coefficient of variance ranging from 2% to 5% and from 2% to 6% at rest and at stress, respectively. For group 3, similar reproducibility coefficients (RC) for MBF were obtained when (68)Ge AC(FBP) was compared with (68)Ge AC(IT) (RC = 0.218) and when CT AC(FBP) was compared with CT AC(IT) (RC = 0.227). Even better reproducibility (lower RC) was found when (68)Ge AC(FBP) was compared with CT AC(FBP) (RC = 0.130) and when (68)Ge AC(IT) was compared with CT AC(IT) (RC = 0.146). CONCLUSION: Our study shows that for the assessment of qualitative and quantitative MBF with a hybrid PET/CT scanner, the use of CT AC (with a tube current of 10 mA) instead of (68)Ge AC provides accurate results.

Beta-adrenergic blockade and myocardial perfusion in coronary artery disease: differential effects in stenotic versus remote myocardial segments.

UNLABELLED: Beta-adrenergic blocking agents are widely used in coronary artery disease (CAD), although their impact on myocardial blood flow (MBF) and coronary flow reserve (CFR) remains unclear. We studied the effect of long-term beta-blocker treatment (carvedilol or metoprolol) on coronary microcirculation in CAD patients using PET. METHODS: Regional and global resting and adenosine-induced hyperemic MBF and CFR were measured with 13N-ammonia and PET in 36 CAD patients before and after 12 wk of oral therapy with either carvedilol, 50 mg/d, or metoprolol, 100 mg/d. RESULTS: Beta-blockade decreased global resting MBF in proportion to cardiac work (from 0.86 +/- 0.20 to 0.77 +/- 0.14 mL/min/g, P < 0.05) without affecting global hyperemic flow. Hyperemic MBF was significantly lower in stenosis-dependent segments than in remote segments (1.76 +/- 0.64 vs. 2.04 +/- 0.67 mL/min/g, P < 0.05) at baseline but was comparable in both after treatment (2.02 +/- 0.68 vs. 1.90 +/- 0.78 mL/min/g, P = not statistically significant [NS]), resulting in a significant CFR increase in stenotic segments (+15%, P < 0.05) but not in remote segments (+9%, P = NS). CONCLUSION: The beneficial effect of beta-adrenergic blockade can be explained by the reduction in oxygen consumption (= decreased demand) but also by a modest improvement in vasodilator capacity (= increased supply). The improvement in CFR is found predominantly in stenosis-dependent rather than remote segments.

Recovery mismatch between myocardial blood flow and cardiac workload after physical exercise: a positron emission tomography study.

AIMS: We studied the interrelation between oxygen consumption and myocardial blood flow (MBF) during recovery. MBF is directly dependent on oxygen consumption. The latter is linearly related to the heart rate-blood pressure product (RPP, bpm × mmHg), an index reflecting external cardiac work. In the immediate post-exercise period, cardiac output decreases considerably. This is expected to be paralleled by a rapid fall in oxygen demand, rendering ischaemia unlikely. Thus, the phenomenon of ST-segment depression during recovery remains unexplained. METHODS AND RESULTS: (15)O-labelled water and positron emission tomography were used to measure MBF in 14 young healthy volunteers (mean age 27 ± 3 years) during the following study conditions: (i) at rest, (ii) during a steady submaximal supine bicycle exercise stress within the scanner, and (iii) during recovery immediately after cessation of exercise. During recovery, RPP decreased by 43% (18 768 ± 1337 vs. 11 652 ± 3224, P < 0.001). In contrast, the associated decrease in MBF (2.52 ± 0.52 vs. 1.93 ± 0.50 mL/min/g, P < 0.001) and perfusion reserve (2.68 ± 0.51 vs. 2.03 ± 0.42, P < 0.001) was significantly less pronounced (-24%, P < 0.01), indicating a relative delay in MBF recovery compared with cardiac work load. CONCLUSION: The mismatch between a rapid decrease in cardiac workload but preserved hyperaemic response early after cessation of physical exercise suggests an uncoupling of cardiac work and MBF during recovery.