Kakuya Kitagawa

Late Gadolinium Enhancement by Cardiovascular Magnetic Resonance Heralds an Adverse Prognosis in Nonischemic Cardiomyopathy

OBJECTIVES We examined whether the presence and extent of late gadolinium enhancement (LGE) by cardiovascular magnetic resonance (CMR) predict adverse outcomes in nonischemic cardiomyopathy (NICM) patients. BACKGROUND Morbidity and mortality is high in NICM patients. However, the clinical course of an individual patient is unpredictable and current risk stratification approaches are limited. Cardiovascular magnetic resonance detects myocardial fibrosis, which appears as LGE after contrast administration and may convey prognostic importance. METHODS In a prospective cohort study, 65 NICM patients with left ventricular (LV) ejection fraction < or =35% underwent CMR before placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death. The CMR images were analyzed for the presence and extent of LGE and for LV function, volumes, and mass. Patients were followed for an index composite end point of 3 cardiac events: hospitalization for heart failure, appropriate ICD firing, and cardiac death. RESULTS A total of 42% (n = 27) of patients had CMR LGE, averaging 10 +/- 13% of LV mass. During a 17-month median follow-up, 44% (n = 12) of patients with LGE had an index composite outcome event versus only 8% (n = 3) of those without LGE (p < 0.001 for Kaplan-Meier survival curves). After adjustment for LV volume index and functional class, patients with LGE had an 8-fold higher risk of experiencing the primary outcome (hazard ratio 8.2, 95% confidence interval 2.2 to 30.9; p = 0.002). CONCLUSIONS A CMR LGE in NICM patients strongly predicts adverse cardiac outcomes. The CMR LGE may represent the end-organ consequences of sustained adrenergic activation and adverse LV remodeling, and its identification may significantly improve risk stratification strategies in this high risk population. (Imaging Techniques for Identifying Factors of Sudden Cardiac Death Risk; NCT00181233).

Adenosine stress 64- and 256-row detector computed tomography angiography and perfusion imaging: a pilot study evaluating the transmural extent of perfusion abnormalities to predict atherosclerosis causing myocardial ischemia.

Background—Multidetector computed tomography coronary angiography (CTA) is a robust method for the noninvasive diagnosis of coronary artery disease. However, in its current form, CTA is limited in its prediction of myocardial ischemia. The purpose of this study was to test whether adenosine stress computed tomography myocardial perfusion imaging (CTP), when added to CTA, can predict perfusion abnormalities caused by obstructive atherosclerosis. Methods and Results—Forty patients with a history of abnormal single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) underwent adenosine stress 64-row (n=24) or 256-row (n=16) detector CTP and CTA. A subset of 27 patients had invasive angiography available for quantitative coronary angiography. CTA and quantitative coronary angiography were evaluated for stenoses ≥50%, and SPECT-MPI was evaluated for fixed and reversible perfusion deficits using a 17-segment model. CTP images were analyzed for the transmural differences in perfusion using the transmural perfusion ratio (subendocardial attenuation density/subepicardial attenuation density). The sensitivity, specificity, positive predictive value, and negative predictive value for the combination of CTA and CTP to detect obstructive atherosclerosis causing perfusion abnormalities using the combination of quantitative coronary angiography and SPECT as the gold standard was 86%, 92%, 92%, and 85% in the per-patient analysis and 79%, 91%, 75%, and 92% in the per vessel/territory analysis, respectively. Conclusions—The combination of CTA and CTP can detect atherosclerosis causing perfusion abnormalities when compared with the combination of quantitative coronary angiography and SPECT.

Computed tomography angiography and perfusion to assess coronary artery stenosis causing perfusion defects by single photon emission computed tomography: the CORE320 study

AIMS To evaluate the diagnostic power of integrating the results of computed tomography angiography (CTA) and CT myocardial perfusion (CTP) to identify coronary artery disease (CAD) defined as a flow limiting coronary artery stenosis causing a perfusion defect by single photon emission computed tomography (SPECT). METHODS AND RESULTS We conducted a multicentre study to evaluate the accuracy of integrated CTA-CTP for the identification of patients with flow-limiting CAD defined by ≥50% stenosis by invasive coronary angiography (ICA) with a corresponding perfusion deficit on stress single photon emission computed tomography (SPECT/MPI). Sixteen centres enroled 381 patients who underwent combined CTA-CTP and SPECT/MPI prior to conventional coronary angiography. All four image modalities were analysed in blinded independent core laboratories. The prevalence of obstructive CAD defined by combined ICA-SPECT/MPI and ICA alone was 38 and 59%, respectively. The patient-based diagnostic accuracy defined by the area under the receiver operating characteristic curve (AUC) of integrated CTA-CTP for detecting or excluding flow-limiting CAD was 0.87 [95% confidence interval (CI): 0.84-0.91]. In patients without prior myocardial infarction, the AUC was 0.90 (95% CI: 0.87-0.94) and in patients without prior CAD the AUC for combined CTA-CTP was 0.93 (95% CI: 0.89-0.97). For the combination of a CTA stenosis ≥50% stenosis and a CTP perfusion deficit, the sensitivity, specificity, positive predictive, and negative predicative values (95% CI) were 80% (72-86), 74% (68-80), 65% (58-72), and 86% (80-90), respectively. For flow-limiting disease defined by ICA-SPECT/MPI, the accuracy of CTA was significantly increased by the addition of CTP at both the patient and vessel levels. CONCLUSIONS The combination of CTA and perfusion correctly identifies patients with flow limiting CAD defined as ≥50 stenosis by ICA causing a perfusion defect by SPECT/MPI.

Quantification of myocardial perfusion using dynamic 64-detector computed tomography.

Objectives:The purpose of this study was to determine the ability of dynamic 64 slice multidetector computed tomography (d-MDCT) to provide an accurate measurement of myocardial blood flow (MBF) during first-pass d-MDCT using semiquantitative and quantitative analysis methods. Materials and Methods:Six dogs with a moderate to severe left-anterior descending artery stenosis underwent adenosine (0.14 mL · kg−1 · min−1) stress d-MDCT imaging according to the following imaging protocol: iopamidol 10 mL/s for 3 seconds, 8 mm × 4 collimation, 400 milliseconds gantry rotation time, 120 kV, and 60 mAs. Images were reconstructed at 1-second intervals. Regions of interest were drawn in the LAD and remote territories, and time-attenuation curves were constructed. Myocardial perfusion was analyzed using a model-based deconvolution method and 2 upslope methods and compared with the microsphere MBF measurements. Results:The myocardial upslope-to-LV-upslope and myocardial upslope-to-LV-max ratio strongly correlated with MBF (R2 = 0.92, P < 0.0001 and R2 = 0.87, P < 0.0001, respectively). Absolute MBF derived by model-based deconvolution analysis modestly overestimated MBF compared with microsphere MBF (3.0 ± 2.5 mL · g−1 · min−1 vs. 2.6 ± 2.7 mL · g−1 · min−1, respectively). Overall, MDCT-derived MBF strongly correlated with microspheres (R2 = 0.91, P < 0.0001, mean difference: 0.45 mL · g−1 · min−1, P = NS). Conclusions:d-MDCT MBF measurements using upslope and model-based deconvolution methods correlate well with microsphere MBF. These methods may become clinically applicable in conjunction with coronary angiography and next generation MDCT scanners with larger detector arrays and full cardiac coverage.

Assessment of Coronary Artery Disease Using Magnetic Resonance Coronary Angiography: A National Multicenter Trial

OBJECTIVES This national multicenter study determined the diagnostic performance of 1.5-T whole-heart coronary magnetic resonance angiography (MRA) in patients with suspected coronary artery disease (CAD). BACKGROUND Whole-heart coronary MRA using steady-state free precession allows noninvasive detection of CAD without the administration of contrast medium. However, the accuracy of this approach has not been determined in a multicenter trial. METHODS Using a 1.5-T magnetic resonance imaging unit, free-breathing steady-state free precession whole-heart coronary MRA images were acquired for 138 patients with suspected CAD at 7 hospitals. The accuracy of MRA for detecting a ≥ 50% reduction in diameter was determined using X-ray coronary angiography as the reference method. RESULTS Acquisition of whole-heart coronary MRA images was performed in 127 (92%) of 138 patients with an average imaging time of 9.5 ± 3.5 min. The areas under the receiver-operator characteristic curve from MRA images according to vessel- and patient-based analyses were 0.91 (95% confidence interval [CI]: 0.87 to 0.95) and 0.87 (95% CI: 0.81 to 0.93), respectively. The sensitivity, specificity, positive and negative predictive values, and accuracy of MRA according to a patient-based analysis were 88% (49 of 56, 95% CI: 75% to 94%), 72% (51 of 71, 95% CI: 60% to 82%), 71% (49 of 69, 95% CI: 59% to 81%), 88% (51 of 58, 95% CI: 76% to 95%), and 79% (100 of 127, 95% CI: 72% to 86%), respectively. CONCLUSIONS Non-contrast-enhanced whole-heart coronary MRA at 1.5-T can noninvasively detect significant CAD with high sensitivity and moderate specificity. A negative predictive value of 88% indicates that whole-heart coronary MRA can rule out CAD.

Diagnostic Performance of Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-MDCT: The CT Angiography and Perfusion Methods of the CORE320 Multicenter Multinational Diagnostic Study

OBJECTIVE Coronary MDCT angiography has been shown to be an accurate noninvasive tool for the diagnosis of obstructive coronary artery disease (CAD). Its sensitivity and negative predictive value for diagnosing percentage of stenosis are unsurpassed compared with those of other noninvasive testing methods. However, in its current form, it provides no information regarding the physiologic impact of CAD and is a poor predictor of myocardial ischemia. CORE320 is a multicenter multinational diagnostic study with the primary objective to evaluate the diagnostic accuracy of 320-MDCT for detecting coronary artery luminal stenosis and corresponding myocardial perfusion deficits in patients with suspected CAD compared with the reference standard of conventional coronary angiography and SPECT myocardial perfusion imaging. CONCLUSION We aim to describe the CT acquisition, reconstruction, and analysis methods of the CORE320 study.

Characterization and Correction of Beam-hardening Artifacts during Dynamic Volume CT Assessment of Myocardial Perfusion

PURPOSE To fully characterize beam-hardening effects caused by iodinated contrast medium in the left ventricular (LV) cavity and aorta in the assessment of myocardial perfusion at computed tomography (CT) and to validate a beam-hardening artifact correction algorithm that considers fluid-filled vessels and chambers important sources of beam hardening. MATERIALS AND METHODS The Johns Hopkins University animal care and use committee approved all procedures. An anatomically correct LV and myocardial phantom to characterize beam-hardening artifacts was designed. Following validation in the phantom, the beam-hardening correction (BHC) algorithm was applied to 256-detector row dynamic volume CT images in a canine ischemia model (n = 5) during adenosine stress, and the effect of beam hardening was determined by comparing regional dynamic volume CT perfusion metrics (myocardial upslope normalized by maximum LV blood pool attenuation) with microsphere-derived myocardial blood flow (MBF). A paired Student t test was used to compare continuous variables from the same subject but under different conditions, while linear regression analysis was performed to estimate the slope and statistical significance of the relationship between CT-derived perfusion metrics and microsphere-derived MBF. RESULTS Beam-hardening artifacts were successfully reproduced in phantom studies and were eliminated with the BHC algorithm. The correlation coefficient of CT-derived perfusion metrics and microsphere-derived MBF improved from 0.60 to 0.74 (P > .05) following correction in the animal model. CONCLUSION Beam-hardening artifacts confound dynamic volume CT assessment of myocardial perfusion. Application of the BHC algorithm is helpful for improving accuracy of myocardial perfusion at dynamic volume CT.

Characterization of Peri-Infarct Zone Heterogeneity by Contrast-Enhanced Multidetector Computed Tomography: A Comparison With Magnetic Resonance Imaging

OBJECTIVES This study examined whether multidetector computed tomography (MDCT) improves the ability to define peri-infarct zone (PIZ) heterogeneity relative to magnetic resonance imaging (MRI). BACKGROUND The PIZ as characterized by delayed contrast-enhancement (DE)-MRI identifies patients susceptible to ventricular arrhythmias and predicts outcome after myocardial infarction (MI). METHODS Fifteen mini-pigs underwent coronary artery occlusion followed by reperfusion. Both MDCT and MRI were performed on the same day approximately 6 months after MI induction, followed by animal euthanization and ex vivo MRI (n = 5). Signal density threshold algorithms were applied to MRI and MDCT datasets reconstructed at various slice thicknesses (1 to 8 mm) to define the PIZ and to quantify partial volume effects. RESULTS The DE-MDCT reconstructed at 8-mm slice thickness showed excellent correlation of infarct size with post-mortem pathology (r2 = 0.97; p < 0.0001) and MRI (r2 = 0.92; p < 0.0001). The DE-MDCT and -MRI were able to detect a PIZ in all animals, which correlates to a mixture of viable and nonviable myocytes at the PIZ by histology. The ex vivo DE-MRI PIZ volume decreased with slice thickness from 0.9 +/- 0.2 ml at 8 mm to 0.2 +/- 0.1 ml at 1 mm (p = 0.01). The PIZ volume/mass by DE-MDCT increased with decreasing slice thickness because of declining partial volume averaging in the PIZ, but was susceptible to increased image noise. CONCLUSIONS A DE-MDCT provides a more detailed assessment of the PIZ in chronic MI and is less susceptible to partial volume effects than MRI. This increased resolution best reflects the extent of tissue mixture by histopathology and has the potential to further enhance the ability to define the substrate of malignant arrhythmia in ischemic heart disease noninvasively.

Evaluation of Left Ventricular Volumes and Ejection Fraction Using Fast Steady-State Cine MR Imaging: Comparison with Left Ventricular Angiography

Previous studies demonstrated that magnetic resonance (MR) imaging consistently underestimated angiographic measurements of left ventricular (LV) volumes. The purpose of this study was to determine whether MR imaging with steady-state free precession acquisition (SSFP) can provide improved accuracy and reproducibility in measuring cardiac function in comparison with fast spoiled gradient echo cine MR imaging (SPGR). Twenty patients with cardiovascular diseases who underwent breath-hold cine MR imaging within one week of LV angiography were studied. Two sets of breath-hold cine MR images were obtained, one with SSFP and another with SPGR. The LV volumes determined by two breath-hold cine MR sequences were compared with the results by LV angiography. SPGR cine MR imaging consistently underestimated angiographic LV volumes. The mean difference of LV end-diastolic volume was -22.5 +/- 14.8 ml (p < 0.001) for short-axis planes and -27.7 +/- 21.5 ml (p < 0.001) for long-axis planes. In contrast, LV volumes measured by the SSFP imaging showed a good agreement with the results by angiography. The mean difference of LV end-diastolic volume was -2.5 +/- 14.3 ml (p = N.S.) for short-axis planes and -10.9 +/- 15.1 ml (p < 0.01) for long-axis planes. Standard error of the estimation in measuring LV end-diastolic volume with the SSFP imaging was 3.9% for short-axis images and 4.9% for long-axis images. These values were 7.2% and 8.7% with the SPGR imaging. In conclusion, the SSFP acquisition can provide accurate and noninvasive assessments of LV volumes and ejection fraction within a reduced imaging time.

Myocardial CT Perfusion Imaging and SPECT for the Diagnosis of Coronary Artery Disease: A Head-to-Head Comparison from the CORE320 Multicenter Diagnostic Performance Study

PURPOSE To compare the diagnostic performance of myocardial computed tomographic (CT) perfusion imaging and single photon emission computed tomography (SPECT) perfusion imaging in the diagnosis of anatomically significant coronary artery disease (CAD) as depicted at invasive coronary angiography. MATERIALS AND METHODS This study was approved by the institutional review board. Written informed consent was obtained from all patients. Sixteen centers enrolled 381 patients from November 2009 to July 2011. Patients underwent rest and adenosine stress CT perfusion imaging and rest and either exercise or pharmacologic stress SPECT before and within 60 days of coronary angiography. Images from CT perfusion imaging, SPECT, and coronary angiography were interpreted at blinded, independent core laboratories. The primary diagnostic parameter was the area under the receiver operating characteristic curve (Az). Sensitivity and specificity were calculated with use of prespecified cutoffs. The reference standard was a stenosis of at least 50% at coronary angiography as determined with quantitative methods. RESULTS CAD was diagnosed in 229 of the 381 patients (60%). The per-patient sensitivity and specificity for the diagnosis of CAD (stenosis ≥50%) were 88% (202 of 229 patients) and 55% (83 of 152 patients), respectively, for CT perfusion imaging and 62% (143 of 229 patients) and 67% (102 of 152 patients) for SPECT, with Az values of 0.78 (95% confidence interval: 0.74, 0.82) and 0.69 (95% confidence interval: 0.64, 0.74) (P = .001). The sensitivity of CT perfusion imaging for single- and multivessel CAD was higher than that of SPECT, with sensitivities for left main, three-vessel, two-vessel, and one-vessel disease of 92%, 92%, 89%, and 83%, respectively, for CT perfusion imaging and 75%, 79%, 68%, and 41%, respectively, for SPECT. CONCLUSION The overall performance of myocardial CT perfusion imaging in the diagnosis of anatomic CAD (stenosis ≥50%), as demonstrated with the Az, was higher than that of SPECT and was driven in part by the higher sensitivity for left main and multivessel disease.