J Cardiovasc Comput Tomogr. 2011; 5(6):357-369

Ghoshhajra BB, Maurovich-Horvat P, Techasith T, Medina HM, Verdini D, Sidhu MS, Blankstein R, Brady TJ, Cury RC

OBJECTIVES: Cardiac CT has the potential to offer comprehensive infarct detection by assessing regional wall motion abnormalities (RWMAs), rest perfusion defects (RPDs), and delayed contrast enhancement (DCE). However, the diagnostic accuracy of these techniques for the detection of myocardial infarction (MI) is unknown.

METHODS: Forty-eight patients with intermediate-to-high probability for coronary artery disease after single-photon emitting CT myocardial perfusion imaging were prospectively enrolled for a research comprehensive 64-detector row dual-source cardiac CT protocol that included cine images for RWMA, first-pass images for RPD, and delayed images for DCE. Blinded readers independently assessed each technique. Subsequently, a final combined analysis (cine + rest + DCE) was performed. The universal definition for MI by the 2007 American Heart Association task force was used as the “gold standard.”

RESULTS: Twenty-four of 48 patients (50%) had infarct by the universal definition. The combined CT analysis was most accurate (90%) with the highest per-patient sensitivity (88%) and specificity (92%) versus individual assessments (RWMA, 79% and 88%; RPD, 67% and 92%; DCE, 79% and 88%). Similar findings were observed on a per-vessel basis analysis. A combination of DCE and cine showed a good accuracy (85%) and high sensitivity (92%).

CONCLUSIONS: Infarct detection with CT is feasible with overall good diagnostic accuracy compared with the universal definition. A combined evaluation that included all techniques (cine, RPD, and DCE) had the highest diagnostic accuracy. These findings may have implications when designing future clinical and research CT protocols for optimal infarct detection.

PMID: 22210535

Heart. 2012; 98(3):238-243

Yiu KH, de Graaf FR, Schuijf JD, van Werkhoven JM, Ajmone Marsan N, Veltman CE, de Roos A, Pazhenkottil A, Kroft LJ, Boersma E, Herzog B, Leung M, Maffei E, Leung DY, Kaufmann PA, Cademartiri F, Bax JJ, Jukema JW

OBJECTIVES: To evaluate the potential age- and gender-specific differences in the incidence and prognostic value of coronary artery disease (CAD) in patients undergoing CT coronary angiography (CTA).

METHODS: In this multicentre prospective registry study, 2432 patients (mean age 57±12, 56% male) underwent CTA for suspected CAD. Patients were stratified into four groups according to age <60 or ≥60 years and, male or female gender.Main outcome measuresA composite end point of cardiac death and non-fatal myocardial infarction.

RESULTS: CTA results were normal in 991 (41%) patients, showed non-significant CAD in 761 (31%) patients and significant CAD in the remaining 680 (28%) patients. During follow-up (median 819 days, 25-75th centile 482-1142) a cardiovascular event occurred in 59 (2.4%) patients. The annualised event rate was 1.1% in the total population (men=1.3% and women=0.9%). In patients aged <60 years, the annualised event rate of male and female patients was 0.6% and 0.5%, respectively. Among patients aged ≥60 years the annualised event rate was 1.9% in male and 1.1% in female patients. Observations on CTA predicted events in male patients, both age <60 and ≥60 years and in female patients age ≥60 years (log-rank test in all groups, p<0.01). However, CTA provided limited prognostic value in female patients aged <60 years (log-rank test, p=0.45).

CONCLUSIONS: After age and gender stratification, CTA findings were shown to be of limited predictive value in female patients aged <60 years as compared with male patients at any age and female patients aged ≥60 years.

PMID: 21917657

JACC Cardiovasc Imaging. 2011; 4(12):1284-1293

Schuleri KH, Centola M, Choi SH, Evers KS, Dawoud F, George RT, Lima JA, Lardo AC

OBJECTIVES: The aim of this study was to use multidetector computed tomography (MDCT) to assess therapeutic effects of myocardial regenerative cell therapies. Cell transplantation is being widely investigated as a potential therapy in heart failure. Noninvasive imaging techniques are frequently used to investigate therapeutic effects of cell therapies in the preclinical and clinical settings. Previous studies have shown that cardiac MDCT can accurately quantify myocardial scar tissue and determine left ventricular (LV) volumes and ejection fraction (LVEF).

METHODS: Twenty-two minipigs were randomized to intramyocardial injection of phosphate-buffered saline (placebo, n = 9) or 200 million mesenchymal stem cells (MSC, n = 13) 12 weeks after myocardial infarction (MI). Cardiac magnetic resonance and MDCT acquisitions were performed before randomization (12 weeks after MI induction) and at the study endpoint 24 weeks after MI induction. None of the animals received medication to control the intrinsic heart rate during first-pass acquisitions for assessment of LV volumes and LVEF. Delayed-enhancement MDCT imaging was performed 10 min after contrast delivery. Two blinded observers analyzed MDCT acquisitions.

RESULTS: MDCT demonstrated that MSC therapy resulted in a reduction of infarct size from 14.3 ± 1.2% to 10.3 ± 1.5% of LV mass (p = 0.005), whereas infarct size increased in nontreated animals (from 13.8 ± 1.3% to 16.5 ± 1.5%; p = 0.02) (placebo vs. MSC; p = 0.003). Both observers had excellent agreement for infarct size (r = 0.96; p < 0.001). LVEF increased from 32.6 ± 2.2% to 36.9 ± 2.7% in MSC-treated animals (p = 0.03) and decreased in placebo animals (from 33.3 ± 1.4% to 29.1 ± 1.5%; p = 0.01; at week 24: placebo vs. MSC; p = 0.02). Infarct size, end-diastolic LV volume, and LVEF assessed by MDCT compared favorably with those assessed by cardiac magnetic resonance acquisitions (r = 0.70, r = 0.82, and r = 0.902, respectively; p < 0.001).

CONCLUSIONS: This study demonstrated that cardiac MDCT can be used to evaluate infarct size, LV volumes, and LVEF after intramyocardial-delivered MSC therapy. These findings support the use of cardiac MDCT in preclinical and clinical studies for novel myocardial therapies.

PMID: 22172785

N Engl J Med. 2011; 365(22):2078-2087

Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, Raichlen JS, Uno K, Borgman M, Wolski K, Nissen SE

OBJECTIVES: Statins reduce adverse cardiovascular outcomes and slow the progression of coronary atherosclerosis in proportion to their ability to reduce low-density lipoprotein (LDL) cholesterol. However, few studies have either assessed the ability of intensive statin treatments to achieve disease regression or compared alternative approaches to maximal statin administration.

METHODS: We performed serial intravascular ultrasonography in 1039 patients with coronary disease, at baseline and after 104 weeks of treatment with either atorvastatin, 80 mg daily, or rosuvastatin, 40 mg daily, to compare the effect of these two intensive statin regimens on the progression of coronary atherosclerosis, as well as to assess their safety and side-effect profiles.

RESULTS: After 104 weeks of therapy, the rosuvastatin group had lower levels of LDL cholesterol than the atorvastatin group (62.6 vs. 70.2 mg per deciliter [1.62 vs. 1.82 mmol per liter], P<0.001), and higher levels of high-density lipoprotein (HDL) cholesterol (50.4 vs. 48.6 mg per deciliter [1.30 vs. 1.26 mmol per liter], P=0.01). The primary efficacy end point, percent atheroma volume (PAV), decreased by 0.99% (95% confidence interval [CI], -1.19 to -0.63) with atorvastatin and by 1.22% (95% CI, -1.52 to -0.90) with rosuvastatin (P=0.17). The effect on the secondary efficacy end point, normalized total atheroma volume (TAV), was more favorable with rosuvastatin than with atorvastatin: -6.39 mm(3) (95% CI, -7.52 to -5.12), as compared with -4.42 mm(3) (95% CI, -5.98 to -3.26) (P=0.01). Both agents induced regression in the majority of patients: 63.2% with atorvastatin and 68.5% with rosuvastatin for PAV (P=0.07) and 64.7% and 71.3%, respectively, for TAV (P=0.02). Both agents had acceptable side-effect profiles, with a low incidence of laboratory abnormalities and cardiovascular events.

CONCLUSIONS: Maximal doses of rosuvastatin and atorvastatin resulted in significant regression of coronary atherosclerosis. Despite the lower level of LDL cholesterol and the higher level of HDL cholesterol achieved with rosuvastatin, a similar degree of regression of PAV was observed in the two treatment groups.

PMID: 22085316

JACC Cardiovasc Imaging. 2011; 4(11):1149-1157

Choi JH, Min JK, Labounty TM, Lin FY, Mendoza DD, Shin DH, Ariaratnam NS, Koduru S, Granada JF, Gerber TC, Oh JK, Gwon HC, Choe YH

OBJECTIVES: Coronary computed tomography angiography (CTA) assessment of calcified or complex coronary lesions is frequently challenging. Transluminal attenuation gradient (TAG), defined as the linear regression coefficient between luminal attenuation and axial distance, has a potential to evaluate the degree of coronary stenosis.

METHODS: We examined the value of TAG in determining the stenosis severity on 64-slice coronary CTA. The value of TAG of 370 major coronary arteries was measured from 7,263 intervals of 5-mm length.

RESULTS: Compared with coronary CTA and invasive coronary angiography, TAG decreased consistently and significantly with maximum stenosis severity on a per-vessel basis, from -1.91 ± 4.25 Hounsfield units/10 mm for diameter stenosis of 0% to 49% to -13.37 ± 9.81 Hounsfield units/10 mm for diameter stenosis of 100% (p < 0.0001). Adding TAG to the interpretation of coronary CTA improved diagnostic accuracy (p = 0.001), especially in vessels with calcified lesions (N = 127; net reclassification improvement 0.095; p = 0.046).

CONCLUSIONS: TAG appears to be able to contribute to improved classification of coronary artery stenosis severity in coronary CTA, especially in severely calcified lesions.

PMID: 22093264

Radiology. 2011; 261(2):428-436

Dedic A, Genders TS, Ferket BS, Galema TW, Mollet NR, Moelker A, Hunink MG, de Feyter PJ, Nieman K

OBJECTIVES: To determine and compare the prognostic value of cardiac computed tomographic (CT) angiography, coronary calcium scoring, and exercise electrocardiography (ECG) in patients with chest pain who are suspected of having coronary artery disease (CAD).

METHODS: This study complied with the Declaration of Helsinki, and the local ethics committee approved the study. Patients (n = 471) without known CAD underwent exercise ECG and dual-source CT at a rapid assessment outpatient chest pain clinic. Coronary calcification and the presence of 50% or greater coronary stenosis (in one or more vessels) were assessed with CT. Exercise ECG results were classified as normal, ischemic, or nondiagnostic. The primary outcome was a major adverse cardiac event (MACE), defined as cardiac death, nonfatal myocardial infarction, or unstable angina requiring hospitalization and revascularization beyond 6 months. Univariable and multivariable Cox regression analysis was used to determine the prognostic values, while clinical impact was assessed with the net reclassification improvement metric.

RESULTS: Follow-up was completed for 424 (90%) patients; the mean duration of follow-up was 2.6 years. A total of 44 MACEs occurred in 30 patients. Four of the MACEs were cardiac deaths and six were nonfatal myocardial infarctions. The presence of coronary calcification (hazard ratio [HR], 8.22 [95% confidence interval {CI}: 1.96, 34.51]), obstructive CAD (HR, 6.22 [95% CI: 2.77, 13.99]), and nondiagnostic stress test results (HR, 3.00 [95% CI: 1.26, 7.14]) were univariable predictors of MACEs. In the multivariable model, CT angiography findings (HR, 5.0 [95% CI: 1.7, 14.5]) and nondiagnostic exercise ECG results (HR, 2.9 [95% CI: 1.2, 7.0]) remained independent predictors of MACEs. CT angiography findings showed incremental value beyond clinical predictors and stress testing (global χ(2), 37.7 vs 13.7; P < .001), whereas coronary calcium scores did not have further incremental value (global χ(2), 38.2 vs 37.7; P = .40).

CONCLUSIONS: CT angiography findings are a strong predictor of future adverse events, showing incremental value over clinical predictors, stress testing, and coronary calcium scores.

PMID: 21873254

Eur Heart J. 2011; 32(18):2218-2227

Gaemperli O, Shalhoub J, Owen DR, Lamare F, Johansson S, Fouladi N, Davies AH, Rimoldi OE, Camici PG

OBJECTIVES: We sought to determine whether intraplaque inflammation could be measured with positron emission tomography/computed tomography angiography (PET/CTA) using (11)C-PK11195, a selective ligand of the translocator protein (18 kDa) (TSPO) which is highly expressed by activated macrophages.

METHODS: (n = 32; mean age 70 ± 9 years) with carotid stenoses (n = 36; 9 symptomatic and 27 asymptomatic) underwent (11)C-PK11195 PET/CTA imaging. (11)C-PK11195 uptake into carotid plaques was measured using target-to-background ratios (TBR). On CTA images, plaque composition was assessed by measuring CT attenuation of the carotid plaque. Eight patients underwent carotid endarterectomy and ultrathin contiguous sections were processed for TSPO and CD68 (using immunohistochemical staining, (3)H-PK11195 autoradiography, and confocal fluorescence microscopy).

RESULTS: Carotid plaques associated with ipsilateral symptoms (stroke or transient ischaemic attack) had higher TBR (1.06 ± 0.20 vs. 0.86 ± 0.11, P = 0.001) and lower CT attenuation [(median, inter-quartile range) 37, 24-40 vs. 71, 56-125 HU, P = 0.01] than those without. On immunohistochemistry and confocal fluorescence microscopy, CD68 and PBR co-localized with (3)H-PK11195 uptake at autoradiography. There was a significant correlation between (11)C-PK11195 TBR and autoradiographic percentage-specific binding (r = 0.77, P = 0.025). Both TBR and CT plaque attenuation had high negative predictive values (91 and 92%, respectively) for detecting symptomatic patients. However, the best positive predictive value (100%) was achieved when TBR and CT attenuation were combined.

CONCLUSIONS: Imaging intraplaque inflammation in vivo with (11)C-PK11195 PET/CTA is feasible and can distinguish between recently symptomatic and asymptomatic plaques. Patients with a recent ischaemic event had ipsilateral plaques with lower CT attenuation and increased (11)C-PK11195 uptake.

PMID:

Eur Heart J. 2011; 32(17):2011-2020

Tandon V, Hall D, Yam Y, Al-Shehri H, Chen L, Tandon K, Beanlands RS, Wells GA, Ruddy TD, Chow BJ

OBJECTIVES: Computed tomographic coronary angiography (CTA) appears to be a useful modality for the detection of obstructive coronary artery disease (CAD). Recent data suggest that CTA may reduce the frequency of normal invasive coronary angiograms. However, there remains concern that the implementation of CTA could increase referrals to invasive coronary angiography (ICA). To further support the clinical acceptance of CTA, it is important to compare CTA to another accepted modality such as single photon emission computed tomography (SPECT). We followed a cohort of 64-slice CTA patients and a matched cohort of Tc-99m SPECT patients to determine downstream referrals for ICA and revascularization.

METHODS: Consecutive CTA patients (without history of revascularization or cardiac transplantation) were prospectively enrolled and compared with a Tc-99m SPECT cohort (matched for age, gender, and Morise score). Each CTA and SPECT was evaluated for obstructive CAD and patients were followed for downstream ICA and revascularization.

RESULTS: Of the 1221 patients in each cohort, 129 (10.6%) CTA patients and 125 (10.2%) SPECT patients were referred to ICA. Of those referred to ICA, obstructive CAD was confirmed in 105 (81.4%) CTA patients and in 88 (70.4%) SPECT patients. Differences in false positive rates were significantly lower in the CTA than the SPECT cohort (9.7 and 25.8%, respectively, P = 0.009). Rates of revascularization were similar in the CTA and SPECT cohorts (6.2 vs. 5.9%, respectively).

CONCLUSIONS: Compared with SPECT, CTA had similar referrals for ICA and revascularization rates but lower false positive rates. Computed tomographic coronary angiography appears to be a viable non-invasive diagnostic modality and does not appear to negatively impact upon ICA resources.

PMID: 21893487

Circ Cardiovasc Imaging. 2011; 4(4):239-244

Feuchtner G, Goetti R, Plass A, Wieser M, Scheffel H, Wyss C, Stolzmann P, Donati O, Schnabl J, Falk V, Alkadhi H, Leschka S, Cury RC

OBJECTIVES: Coronary computed tomography angiography (CTA) enables accurate anatomic evaluation of coronary artery stenosis, however lacking information about hemodynamical significance. The aim of this study was to evaluate 128-slice myocardial CT perfusion (CTP) imaging with adenosine stress using a high-pitch mode, in comparison with cardiac magnetic resonance imaging (CMR).

METHODS: 39 patients with intermediate-to-high coronary risk profile underwent adenosine stress 128-slice dual source CTP (128×0.6mm, 0.28s). Among those, 30 patients (64±10y, 6% females) also underwent adenosine stress CMR (1.5T). The 2-steps CTP protocol consisted of: 1) Adenosine stress-CTP using a high-pitch factor (3.4) ECG-synchronized spiral mode and 2) rest-CTP/coronary-CTA using either high-pitch (HR<63bpm) or prospective ECG-triggering (HR>63bpm). Results were compared to CMR and to invasive angiography (IA) in 25 patients.

RESULTS: The performance of stress-CTP for detection of myocardial perfusion defects compared to CMR was: sens. 96%, spec. 88%, PPV 93%, NPV 94% (per vessel), and sens. 78%, spec. 87%, PPV 83%, NPV 84% (per segment). The accuracy of stress-CTP for imaging of reversible ischemia compared to CMR was: sens 95%, spec 96%, PPV 95%, NPV 96% (per vessel). In 25 patients who underwent IA, the accuracy of CTA for detection of stenosis >70% was (per segment): sens. 96%, spec. 88%, PPV 67%, NPV 98.9%. The accuracy improved from 84% to 95% after adding stress CTP to CTA. Radiation exposure of the entire stress/rest CT protocol was only 2.5mSv.

CONCLUSIONS: Adenosine-induced stress 128-slice dual source high-pitch myocardial CTP allows for simultaneously assessment of reversible myocardial ischemia and coronary stenosis with good diagnostic accuracy as compared to CMR and IA, at a very low radiation exposure.

PMID: 21862731

Lancet. 2011; 378(9792):684-692

Blaha MJ, Budoff MJ, DeFilippis AP, Blankstein R, Rivera JJ, Agatston A, O'Leary DH, Lima J, Blumenthal RS, Nasir K

PMID: