The Application of Conditional Probability to Harmonize Nuclear Cardiology Test Results.

Both exercise single photon emission computed tomography (SPECT) imaging and myocardial perfusion imaging with positron emission tomography produce multiple outcome variables. These include the stress electrocardiogram (ECG), visual perfusion assessment and quantitative myocardial blood flow. Bayes' analysis using conditional probability allows the distillation of multiple test results into a single probability of disease for individual patients. This paper examines the application of conditional probability analysis to two noninvasive modalities that generate multiple outcome results: exercise ECG combined with SPECT imaging and vasodilator RB-82 positron emission tomography perfusion imaging combined with quantitative measure of absolute myocardial blood flow. In this manner, a single probability of disease incorporating all the available data is generated for an individual patient.

The chest pain guidelines revisited: cherry picking from the frequentist tree.

The new chest pain guideline document was recently released. The biggest changes are in the recommendations for intermediate and high-risk patients with known and unknown CAD. Coronary CT angiography has been recommended as the preferred imaging test for patients < 65 years old with chest pain. This paper will review the major evidence and omissions in the document that prompted that recommendation and provide thoughts on potential actions going forward.

Harmonizing multimodality imaging results using Bayesian analysis: the case of CT coronary angiography and CT-derived fractional flow reserve.

Coronary computed tomographic angiography (CCTA) may provide both anatomic and CT fractional flow reserve data (CTFFR). The objective is to use Bayesian analysis to develop a model wherein the probability of significant coronary artery disease (CAD) by CTFFR can be determined given the prior probability (P) of the combined clinical and CCTA result. 172 patients referred for CCTA and subsequently underwent coronary angiography were automatically referred to CTFFR analysis. A clinical P risk score (CRS) was calculated per patient. CCTA exams were scored using CAD-RADS classification. CTFFR results were generated. CAD was defined as ≥ 3 RAD class for CCTA and ≤ .80 by CTFFR. P was calculated using CCTA and CTFFR accuracy from a prior clinical trial: post-test P for the CCTA result used the CRS as the prior risk, and CTFFR P used the post-test CRS + CCTA P as the prior risk (tri-variable). Patients were classified for each model into low (< 5%), intermediate, (5-70%) and high (> 70%) risk groups. There were 100 patients (58%), who had significant CAD at angiography. 58 patients had discordant CCTA/CTFFR results. The inclusion of the CRS and CRS + CCTA in the prior progressively reduced the intermediate risk cohort from 83 to 41% (p < 0.0001). Correct classifications (low-risk, negative angiogram plus high-risk, positive angiogram) increased by model: CRS = 12%, CRS + CCTA = 25%, CRS + CTFFR = 33%, CRS + CCTA + CTFFR = 44% (p < 0.001). Incorrect classifications were reduced to 15%. The tri-variable model performed better than either CCTA or CTFFR alone for all patients and for the sub-group with discordant imaging results. Discrepant CCTA and CTFFR results are present in one third of patients. The use of both the CRS and CCTA as the prior risk synergistically maximized the accuracy of the accuracy of the CTFFR technique.

High dose intracoronary N-acetylcysteine in a porcine model of ST-elevation myocardial infarction.

We sought to evaluate the safety and efficacy of N-acetylcysteine (NAC) on ischemia and reperfusion in a pig model focusing on cardio-renal protection. High doses of NAC may provide protection from contrast induced nephropathy (CIN). NAC has also been demonstrated to reduce myocardial infarction size and improve left ventricular function after ischemia in both humans and animals studies. In this study we tested the safety and cardiorenal protective efficacy of intracoronary NAC delivered in the radiographic contrast agent in a pig model that simulates the catheter based reperfusion therapy of ST elevation myocardial infarctions. 27 pigs underwent 45 min of ischemia after surgical ligation of distal left descending coronary artery. With coronary reperfusion the animals received at total of 200 mL of the contrast agent Iopamidol with and without NAC to mimic radiographic contrast use during invasive reperfusion therapy. At 24 h the following endpoints were compared: LV function (MRI, echocardiography), myocardial injury (infarct size, area-at-risk, troponin, creatinine kinase) and CIN (creatinine, BUN and renal histology). The effects of NAC on platelet reactivity were also evaluated. Intracoronary administration of NAC administered in the contrast agent is safe. NAC reduces platelet reactivity and there was a trend towards a better cardiac function at 24 h. There was no significant difference in the size of the myocardial infarction. In this model of ischemia-reperfusion high dose NAC did not protect from CIN. High dose intracoronary NAC administered with the radiographic contrast is safe but does not provide significant cardio-renal protection.

Myocardial perfusion imaging with first-pass computed tomographic imaging: Measurement of coronary flow reserve in an animal model of regional hyperemia.

BACKGROUND: The accurate assessment of myocardial blood flow (MBF) is a potential adjunct to the anatomy of CT coronary angiography. PURPOSE: To compare semi-quantitative parameters from first-pass CT (FP CT) imaging with absolute measures of MBF in an animal model of altered MBF. METHODS: A pig model of intracoronary adenosine (n = 8) was used during FP CT. This produces a zone with hyperemic MBF and a control zone within a slice. A subset of these animals also underwent LAD occlusion with imaging. Fluorescent microspheres (Mcsp) were injected into the left atrium to determine absolute MBF concurrent with CT imaging. Pigs were placed in a 64-slice (Philips) CT with acquisition performed during IC adenosine and occlusion. A 40% dilution of Iopamidol 370 (1 mL/kg) was injected IV at 5 mL/second. CT acquisition was ECG gated over 40 cardiac phases with the following parameters: 180 degrees axial mode (pitch = 0), field of view = 250 mmsq, 512 x 512 matrix, slice thickness = 2.5 mm x 10 slices, temporal resolution = 330 ms, 120 kV, 495 ma. Mcsp were injected immediately following CT imaging. The heart was sectioned into 2.5 mm slices to match the CT images and segmented. Time attenuation curves (TAC) were generated from CT in intervention and control zones based on Mcsp values. Mcsp coronary flow reserve (CFR) = hyperemic/control MBF, and CT CFR was derived from intervention/control area under curve from baseline corrected TIC. RESULTS: MBF control = .65 +/- .28, MBF adenosine = 2.6 +/- .7 mL/min/g (P < .0001). CFR = 4.1 +/- 1.1, CT CFR = 4.3 +/- 1.4 (P = NS). There was a significant (r = .94, P < .0001) correlation between CFR and CT CFR. CONCLUSIONS: CT first-pass myocardial perfusion imaging is feasible using a simple semi-quantitative analysis which provides reasonable estimates of MBF.

Accuracy of cardiac magnetic resonance of absolute myocardial blood flow with a high-field system: comparison with conventional field strength.

OBJECTIVES: The aim of this study was to determine the accuracy of cardiac magnetic resonance (CMR) first pass (FP) perfusion measures of absolute myocardial blood flow (MBF) with a 3.0-T magnet and compare these measures with FP perfusion at 1.5-T with absolute MBF by labeled microspheres as the gold standard. BACKGROUND: First-pass magnetic resonance (MR) myocardial perfusion imaging can quantify MBF, but images are of low signal at conventional magnetic field strength due to the need for rapid acquisition. METHODS: A pig model was used to alter MBF in a coronary artery during FP CMR (intracoronary adenosine followed by ischemia). This produces an active zone with a range of MBF and a control zone. Microspheres were injected into the left atrium with concurrent reference sampling. FP MR perfusion imaging was performed at 1.5-T (n = 9) or 3.0-T (n = 8) with a saturation-recovery gradient echo sequence in short-axis slices during a bolus injection of 0.025 mmol/kg gadolinium-diethylenetriamine pentaacetic acid. Fermi function deconvolution was performed on active and control region of interest from short-axis slices with an arterial input function derived from the left ventricular cavity. These MR values of MBF were matched to microsphere values obtained from short-axis slices at pathology. RESULTS: Occlusion MBF was 0.21 +/- 0.26 ml/min/g, adenosine MBF was 2.28 +/- 0.99 ml/min/g, and control zone MBF was 0.70 +/- 0.22 ml/min/g. The correlation of MR FP CMR with microsphere was close for both field strengths: 3.0-T, r = 0.98, p < 0.0001 and 1.5-T, r = 0.95, p < 0.0001. The 95% confidence limits of agreement were slightly narrower at 3.0-T (3.0-T = 0.49 ml/min/g, 1.5-T = 0.68 ml/min/g, p < 0.05). The FP CMR image characteristics were better at 3.0-T (noise and contrast enhancement were both superior at 3.0-T). In myocardial zones where MBF <0.50 ml/min/g, the correlation with microspheres was closer at 3.0-T (r = 0.55 at 1.5-T, r = 0.85 at 3.0-T). CONCLUSIONS: Absolute MBF by FP perfusion imaging is accurate at both 1.5- and 3.0-T. Signal quality is better at 3.0-T, which might confer a benefit for estimating MBF in ischemic zones.

Estimation of absolute myocardial blood flow during first-pass MR perfusion imaging using a dual-bolus injection technique: comparison to single-bolus injection method.

PURPOSE: To compare the dual-bolus to single-bolus quantitative first-pass magnetic resonance myocardial perfusion imaging for estimation of absolute myocardial blood flow (MBF). MATERIALS AND METHODS: Dogs had local hyperemia of MBF in the left anterior descending (LAD) coronary artery (intracoronary adenosine). Animals (n = 6) had sequential single- and dual-bolus perfusion studies with microsphere determination of absolute MBF. Perfusion imaging was performed using a saturation-recovery gradient-echo sequence. Absolute MBF was by Fermi function deconvolution and compared to transmural, endocardial, and epicardial microsphere values in the same region of interest (ROI). RESULTS: Signal and contrast were significantly higher for the dual-bolus perfusion images. The correlation with MBF by microspheres was r = 0.94 for the dual-bolus method and r = 0.91 for the single-bolus method. There was no significant difference between MRI and microsphere MBF values for control or hyperemic zones for transmural segments for either technique. When the ROI was reduced to define endocardial and epicardial zones, single-bolus MR first-pass imaging significantly overestimated MBF and had a significantly larger absolute error vs. microspheres when compared to dual-bolus perfusion. CONCLUSION: Both single-bolus and dual-bolus perfusion methods correlate closely with MBF but the signal and contrast of the dual-bolus images are greater. With smaller nontransmural ROIs where signal is reduced, the dual-bolus method appeared to provide slightly more accurate results.

Gated SPECT imaging to detect changes in myocardial blood flow during progressive coronary occlusion.

BACKGROUND: The ability to track dynamic changes in myocardial blood flow (MBF) and wall motion with serial gated perfusion imaging may be a limiting factor in assessing new therapies. The purpose of this study was to determine whether gated Tc-99 m sestamibi (MIBI) SPECT imaging can track small changes in MBF in a model of progressive ischemia. METHODS: Eight pigs (20 kg) underwent lateral thoracotomy for placement of an ameroid constrictor on the left circumflex coronary artery (LCX) and indwelling femoral and left atrial catheters for serial microsphere determinations of absolute MBF. Animals underwent concurrent left atrial microsphere and Tc-99 m sestamibi (0.3 mCi/Kg IV) injections at weekly intervals over 6 weeks per animal. Gated SPECT imaging was acquired for each injection using high resolution collimation and standard processing. The animals were sacrificed on day 42. Mean signal intensity (SI) from regions of interest (ROI) corresponding to control and ischemic MBF by microspheres was measured for three SPECT short-axis images. Mean contrast ratio (MCR) was calculated from the ratio of ischemic to control SI per slice. Regional wall motion (RWM) from gated images was scored 1-5 using a 16 segment model and a score index (RWMI) was calculated. RESULTS: MBF decreased progressively (27% below resting values [P < 0.0001]) but with a clear and significant partial recovery by day 42 (13% improvement from peak ischemia, [P < 0.01]). SPECT perfusion and gated RWM closely paralleled the dynamic pattern of MBF caused by the ameroid constrictor. SPECT MCR decreased 21% from baseline scans in the LCX territory (P < 0.0001) and improved 11% from peak ischemia (P < 0.01) while the gated RWMI (1.0 at baseline) peaked at 1.36 and improved to 1.13 by day 42. CONCLUSION: Gated SPECT-a technique readily available-tracks dynamic changes in MBF closely with both perfusion and RWM. For trials of new therapies for the alleviation of chronic ischemia, these findings have direct implications for measuring efficacy.

Imaging and quantifying valvular heart disease using magnetic resonance techniques.

Echocardiography remains the cornerstone of noninvasive valvular heart disease evaluation. There are instances where MRI can be of use. Aside from the obvious advantage where limited acoustic windows are present, cardiac magnetic resonance (CMR) allows for imaging in any desired plane, and advantage can be taken of the ability to align with any regurgitant or stenotic flow jet. The high spatial resolution and contrast allow for accurate detail of valvular anatomy, but it must be remembered that the images represent a composite of eight to 12 heart cycles. For visualizing multiple valvular abnormalities simultaneously, cardiac MRI has a distinct advantage. Finally, a CMR valvular examination can be combined with accurate assessments of left and right ventricular function, myocardial stress perfusion imaging, and detailed viability determinations in a single examination. This provides a comprehensive presurgical evaluation of cardiac physiology.

Determining myocardial viability in chronic ischemic left ventricular dysfunction: a prospective comparison of rest-redistribution thallium 201 single-photon emission computed tomography, nitroglycerin-dobutamine echocardiography, and intracoronary myocardial contrast echocardiography.

BACKGROUND: Detection of viable myocardium (VM) has important therapeutic implications for chronic ischemic left ventricular (LV) systolic dysfunction. We compared the ability of nitroglycerin-dobutamine echocardiography (NTG-DE), intracoronary myocardial contrast echocardiography (MCE), and rest-redistribution thallium 201 single-photon emission computed tomography (RRT-SPECT) to detect VM in this setting. METHODS: Patients with LV ejection fraction (LVEF) <40% and multivessel coronary disease suitable for revascularization underwent NTG-DE, MCE, RRT-SPECT, and radionuclide ventriculography to determine baseline LVEF. Myocardial contrast echocardiography was performed using intracoronary injection of Albunex. Patients who underwent revascularization had 3-month postprocedural radionuclide ventriculography and transthoracic echocardiography to assess functional recovery. RESULTS: Of 512 myocardial segments in the 32 patients studied, 309 were akinetic or dyskinetic at baseline. Nitroglycerin alone increased regional thickening in 20% of segments with contractile reserve. By RRT-SPECT, 93% of nitroglycerin-responsive segments were viable. Myocardial contrast echocardiography had up to 85% sensitivity and 74% specificity for detection of VM diagnosed by RRT-SPECT. In the 23 patients who underwent revascularization, 54% of akinetic segments showed improved contractility, and mean LVEF increased from 32% to 37% (P = .04). Sensitivities and specificities for detecting functional recovery were 95% and 37% for RRT-SPECT, up to 87% and 48% for MCE, and 63% and 83% for a biphasic response during NTG-DE. CONCLUSIONS: In patients with chronic ischemic LV dysfunction, RRT-SPECT had the highest sensitivity, and NTG-DE, the best specificity for detection of VM. Nitroglycerin facilitated detection of VM and may be a useful adjunct to dobutamine stimulation.

Myocardial tagging and strain analysis at 3 Tesla: comparison with 1.5 Tesla imaging.

PURPOSE: To determine whether imaging at 3 T could improve and prolong the tag contrast compared to images acquired at 1.5 T in normal volunteers, and whether such improvement would translate into the ability to perform strain measurements in diastole. MATERIALS AND METHODS: Normal volunteers (N = 13) were scanned at 1.5 T (GE Signa CV/i) and 3.0 T (GE VH/i). An ECG-triggered, segmented k-space, spoiled-gradient-echo grid-tagged sequence was used during cine acquisition. Tag contrast was determined by the difference of the mean signal intensity (SI) of the tagline to the mean SI of the myocardium divided by the standard deviation (SD) of the noise (CNR(tag)). Matched short-axis (SA) slices were analyzed. Strain measurements were performed on images using a 2D strain analysis software program (harmonic phase (HARP)). RESULTS: The average CNR(tag) over the cardiac cycle was superior at 3 T compared to 1.5 T for all slices (3 T: 23.4 +/- 12.1, 1.5 T: 9.8 +/- 8.4; P < 0.0001). This difference remained significant at cycle initiation, end-systole, and the end R-R interval (at cycle termination: 3 T = 14.0 +/- 11.0 vs. 1.5 T = 4.4 +/- 3.5; P < 0.01). Strain measures were obtainable only in early systole for 1.5 T images, but were robust throughout the entire R-R interval for 3 T images. CONCLUSION: Imaging at 3 T had a significant benefit for myocardial tag persistence through the cardiac cycle. The improvement allowed strain analysis to be performed into diastole.

Grade 3 ischemia on the admission electrocardiogram predicts rapid progression of necrosis over time and less myocardial salvage by primary angioplasty.

BACKGROUND: Among patients with ST-elevation acute myocardial infarction, those with terminal QRS distortion (grade 3 ischemia) have higher mortality and larger infarct size (IS) than patients without QRS distortion (grade 2 ischemia). METHODS: We assessed the relation of baseline electrocardiographic ischemia grades to area at risk (AR) and myocardial salvage [100 (AR-IS)/AR] in 79 patients who underwent primary angioplasty for first ST-elevation acute myocardial infarction and had technetium Tc 99m sestamibi single-photon emission computed tomography before angioplasty (AR) and at predischarge (IS). Patients were classified as having grade 2 ischemia (ST elevation without terminal QRS distortion in any of the leads, n = 48), grade 2.5 ischemia (ST elevation with terminal QRS distortion in 1 lead, n = 16), or grade 3 ischemia (ST elevation with terminal QRS distortion in >2 adjacent leads, n = 15). RESULTS: Time to treatment was comparable among groups. AR was comparable among groups (38% +/- 20%, 33% +/- 23%, and 34% +/- 23%, respectively; P = .70). There were no differences among groups in residual myocardial perfusion (severity index 0.28 +/- 0.12, 0.29 +/- 0.16, and 0.30 +/- 0.15 in grades 2, 2.5, and 3 ischemia, respectively; P = .97). In contrast, there was a trend toward lower myocardial salvage (45% +/- 32%) in the grade 3 group than in the grade 2 (65% +/- 33%) and grade 2.5 (65% +/- 40%) groups ( P = .16). Salvage was dependent on time only in the grade 3 group. Spearman rank correlation coefficients between time to treatment and percentage salvage were 0.003 ( P = .99), -0.24 ( P = .38), and -0.63 ( P = .022) for grades 2, 2.5, and 3, respectively. CONCLUSIONS: Patients with grade 3 ischemia have rapid progression of necrosis over time and less myocardial salvage. This admission pattern is a predictor of myocardial salvage by primary angioplasty.