Application of Cardiovascular Computed Tomography to the Assessment of Patients With Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy is a common inherited cardiac condition in which regional myocardial thickening and scarring can lead to a range of symptoms including breathlessness, dizziness, chest pain, and collapse with loss of consciousness. It is vital to be able to understand the mechanisms behind these epiphenomena and to be able to distinguish, for example, between syncope because of arrhythmia versus syncope because of mechanical outflow tract obstruction. Therefore, we require a technique that can characterize anatomy, physiology, and myocardial substrate. Traditionally, this role has been the preserve of cardiac magnetic resonance (CMR) imaging. This review makes the case for cardiac computed tomography (CT) as an alternative imaging method. We review the use of functional CT to identify the components of outflow tract obstruction (and obstruction at other levels, which may be simultaneous), and as an aid to interventional and surgical planning. We demonstrate the added value of multiplanar isotropic reformats in this condition, particularly in cases where the diagnosis may be more challenging or where complications (such as early apical aneurysm) may be difficult to recognize with 2-dimensional techniques. In conclusion, our aim is to convince readers that cardiac CT is a highly valuable and versatile tool, which deserves wider usage and greater recognition in those caring for patients with hypertrophic cardiomyopathy.

Long-term health outcomes and cost-effectiveness of coronary CT angiography in patients with suspicion for acute coronary syndrome.

BACKGROUND: Randomized trials have shown favorable clinical outcomes for coronary CT angiography (CTA) in patients with suspected acute coronary syndrome (ACS). Our goal was to estimate the cost-effectiveness of coronary CTA as compared to alternative management strategies for ACP patients over lifetime. METHODS: Markov microsimulation model was developed to compare cost-effectiveness of competitive strategies for ACP patients: 1) coronary CTA, 2) standard of care (SOC), 3) AHA/ACC Guidelines, and 4) expedited emergency department (ED) discharge protocol with outpatient testing. ROMICAT-II trial was used to populate the model with low to intermediate risk of ACS patient data, whereas diagnostic test-, treatment effect-, morbidity/mortality-, quality of life- and cost data were obtained from the literature. We predicted test utilization, costs, 1-, 3-, 10-year and over lifetime cardiovascular morbidity/mortality for each strategy. We determined quality adjusted life years (QALY) and incremental cost-effectiveness ratio. Observed outcomes in ROMICAT-II were used to validate the short-term model. RESULTS: Estimated short-term outcomes accurately reflected observed outcomes in ROMICAT-II as coronary CTA was associated with higher costs ($4,490 vs. $2,513-$4,144) and revascularization rates (5.2% vs. 2.6%-3.7%) compared to alternative strategies. Over lifetime, coronary CTA dominated SOC and ACC/AHA Guidelines and was cost-effective compared to expedited ED protocol ($49,428/QALY). This was driven by lower cardiovascular mortality (coronary CTA vs. expedited discharge: 3-year: 1.04% vs. 1.10-1.17; 10-year: 5.06% vs. 5.21-5.36%; respectively). CONCLUSION: Coronary CTA in patients with suspected ACS renders affordable long-term health benefits as compared to alternative strategies.

Complementary pre-operative risk assessment using coronary computed tomography angiography and nuclear myocardial perfusion imaging in non-cardiac surgery: A VISION-CTA sub-study.

BACKGROUND: The incremental value and optimal utilization of non-invasive testing for prediction of peri-operative cardiac events during non-cardiac surgery are not clear. METHODS: A sub-study of VISION-CTA was performed using patients who underwent both coronary computed tomography angiography (CCTA) and nuclear myocardial perfusion imaging (MPI) as part of their pre-operative assessment. CCTA images were compared with MPI to determine the correlation between ischemia and obstructive coronary artery disease (CAD). Patients were followed post-operatively for 30 days and primary outcomes were all-cause death and non-fatal myocardial infarction. The predictive capacity of CCTA and nuclear MPI in predicting peri-operative major adverse cardiac event (MACE) was analyzed. RESULTS: A total of 55 patients (mean age 68.5 ± 8.4 years, 80.0% male) were analyzed. There was a strong correlation between the degree of obstructive CAD and the severity of perfusion abnormalities. Patients with severe CAD (≥ 70% stenosis) had a higher summed stress score than those without severe CAD [4.88 ± 1.22 and 1.30 ± 0.62, respectively (P < .05)]. Similarly summed difference score was significantly higher in patients with severe CAD [1.33 ± 0.46 and 0.17 ± 0.17 (P < .05)]. At 30 days there was a total of 8 (14.5%) MACE. The rate of MACE was higher in patients with severe CAD than those without (20.7% and 7.7%, respectively). Myocardial ischemia appeared to be predictive of MACE with an unadjusted odds ratio of 14.63 (P = .003). The predictive capacity of MPI further improved when only those patients with severe CAD were included (33.00) with a sensitivity, specificity, positive predictive value, and negative predictive value of 100% (79.4-100.0), 72.7% (49.8-89.3), 50.0% (21.1-78.9), and 100% (79.4-100.0), respectively. CONCLUSION: Although patients with significant obstructive disease are at risk of peri-operative MACE, the absolute event rate is low. Our data, albeit hypothesis generating, suggest that the peri-operative risk may be refined further by employing nuclear MPI in those with obstructive disease on CCTA.

Are iso-osmolar, as compared to low-osmolar, contrast media cost-effective in patients undergoing cardiac catheterization? An economic analysis.

PURPOSE: Contrast-induced acute kidney injury is a prominent complication following cardiac catheterization, though the risk has progressively decreased in recent times with appropriate risk stratification and use of safer contrast agents. Despite data supporting further lowering of risk with the iso-osmolar agent, iodixanol, uptake has lagged, perhaps due to increased upfront cost of this agent. We undertook an economic analysis to estimate the cost-effectiveness of a strategy utilizing iodixanol compared to using a low-osmolar contrast agent. METHODS: We created a Markov model to evaluate the two strategies, and included a differential relative risk of contrast-induced acute kidney injury, based on a systematic review of the literature. Downstream clinical events, including need for dialysis and mortality, were modeled using data from existing published literature. A third-party payer perspective was utilized for the analysis and presentation of the primary economic analysis. RESULTS: The strategy of using iodixanol dominated in both the low-risk and high-risk base case analyses. However, the difference was quite small in the low-risk scenario (lifetime cost: C$678,034 vs. C$678,059 and life expectancy: 19.80 vs. 19.72 years). The difference was more marked (life expectancy 15.65 vs. 14.15 years and cost C$680,989 vs. C$682,023) in the high-risk case analysis. This was robust across most of the variables tested in sensitivity analyses. CONCLUSION: The use of iodixanol, compared with low-osmolar contrast agents, for cardiac catheterization, results in a small benefit clinical outcomes, and in a savings in direct healthcare costs. Overall, our analysis supports the use of iodixanol for cardiac catheterization, especially in patients at high risk of acute kidney injury.

Sex Differences in Associations of Arterial Compliance With Coronary Artery Plaque and Calcification Burden.

BACKGROUND: Coronary artery disease is a leading killer of women. Arterial stiffness predicts myocardial infarction, and postmenopausal women have lower arterial compliance (AC) than men. We hypothesized that lower AC would be associated with greater burden of coronary artery plaque and calcification, and that these associations would be stronger in women than men. METHODS AND RESULTS: We evaluated 3639 consecutive adults without coronary artery disease history who had coronary computed tomography between 2006 and 2014. Coronary artery calcification was calculated using the Agatston method. Plaque extent was assessed by the number of arterial segments with visible plaque divided by the number of visualized segments ×100 (percent plaque score). Indexed AC was calculated as stroke volume index/central pulse pressure. We used step-wise multivariable linear regression to assess associations of log indexed AC with log (percent plaque score+1) and log (coronary artery calcification+1). Sex-specific models were performed if the interaction sex×AC was significant. Mean age was 57±11 years, 53% were men, and 71% were hypertensive. Interaction term sex×AC was significant for both models (P=0.008 for percent plaque score and 0.022 for coronary artery calcification). Lower indexed AC was associated with higher percent plaque score and coronary artery calcification in women (ß±SE: -0.231±0.113, P=0.042 and -0.334±0.166, P=0.044, respectively), but not in men (ß±SE: -0.062±0.104, P=0.551 and 0.114±0.173, P=0.510, respectively). CONCLUSIONS: Lower AC is associated with greater burden of coronary artery plaque and calcification in women, but not in men. Our findings highlight low AC as a correlate of more-advanced coronary artery disease and as a potential link to the worse cardiovascular outcomes in women.

Prognostic Significance of Nonobstructive Left Main Coronary Artery Disease in Women Versus Men: Long-Term Outcomes From the CONFIRM (Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter) Registry.

BACKGROUND: Patients with obstructive (≥50% stenosis) left main (LM) coronary artery disease (CAD) are at high risk for adverse events; prior studies have also documented worse outcomes among women than men with severe multivessel/LM CAD. However, the prognostic significance of nonobstructive (1%-49% stenosis) LM CAD, including sex-specific differences, has not been previously examined. METHODS AND RESULTS: In the long-term CONFIRM (Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter) registry, patients underwent elective coronary computed tomographic angiography for suspected CAD and were followed for 5 years. After excluding those with obstructive LM CAD, 5166 patients were categorized as having normal LM or nonobstructive LM (18% of cohort). Cumulative 5-year incidence of death, myocardial infarction, or revascularization was higher among patients with nonobstructive LM than normal LM in both women and men: women (34.3% versus 15.4%; P<0.0001); men (24.6% versus 18.2%; P<0.0001). A significant interaction existed between sex and LM status for the composite outcome (P=0.001). In multivariable Cox regression, the presence of nonobstructive LM plaque increased the risk for the composite outcome in women (adjusted hazard ratio, 1.48; P=0.005) but not in men (adjusted hazard ratio, 0.98, P=0.806). In subgroup analysis, women with nonobstructive LM CAD had a nearly 80% higher risk for events than men with nonobstructive LM CAD (adjusted hazard ratio, 1.78; P=0.017); sex-specific interactions were not observed across other patterns (eg, location or extent) of nonobstructive plaque. CONCLUSION: Nonobstructive LM CAD was frequently detected on coronary computed tomographic angiography and strongly associated with adverse events among women. Recognizing the sex-specific prognostic significance of nonobstructive LM plaque may augment risk stratification efforts.

Cardiac CT assessment of left ventricular mass in mid-diastasis and its prognostic value.

AIMS: To determine the influence of cardiac motion on measurements of left ventricular (LV) mass obtained with 64-slice computed tomography (CT) and to elucidate the prognostic value of LV mass on major adverse cardiac events (MACE) and all-cause mortality. Increased LV mass has been linked with MACE. Although Cardiac CT allows measurement of LV anatomy, it is susceptible to motion artefacts often requiring image acquisition during diastasis. There is a need to understand variability in LV mass measurements across phases of the cardiac cycle, and whether mid-diastolic measurements have prognostic value. METHODS AND RESULTS: The study comprised two equally sized cohorts of patients that had undergone retrospectively gated cardiac CT: patients who had MACE and/or all-cause death at follow-up and a matched (age, sex, and risk factors) event-free cohort. LV mass was measured at mid-diastole, end-diastole, and end-systole. Correlation and agreement between phases were determined. The incremental value of mid-diastolic hypertrophy (LVH) over the National Cholesterol Education Programme (NCEP) risk was performed for LV mass indices normalized to body surface area (LVMIBSA) or weight (LVMIWeight). Of 166 patients, 31.3% experienced MACE and 28.9% died of any cause (follow-up 22.9 ± 13.4 months). LV mass at all cardiac phases were strongly correlated (r > 0.94). Mean mid-diastolic LVMIBSA was higher in the cohort with events (93.7 vs. 80.7 g/m2, P= 0.008) as was LVMIWeight (2.26 vs. 1.88 g/kg, P = 0.001). LVMIBSA and LVMIWeight had prognostic value incremental to NCEP with 1.85 and 2.47 hazard ratios, respectively. CONCLUSIONS: Measurement of LV mass can be obtained by cardiac CT images obtained at mid-diastasis. LV mass measurements obtained at mid-diastasis have prognostic value.

Assessment of left ventricular ejection fraction using low radiation dose computed tomography.

BACKGROUND: Cardiac CT is a non-invasive modality with the ability to estimate LVEF. However, given its limited temporal resolution and radiation, there has been initial resistance to use CT to measure LVEF. Developing an accurate, fast, low radiation dose protocol is desirable. OBJECTIVE: The objective of this study is to demonstrate that a 'low radiation dose' 64 slice cardiac computed tomography (CT) protocol is feasible and can accurately measure left ventricular ejection fraction (LVEF) while delivering a radiation dose lower than radionuclide angiography (RNA). METHODS: Patients undergoing RNA were prospectively screened and enrolled to undergo a 'low-dose' 64 slice CT LVEF protocol. LVEF measures, duration of each study and radiation dose between CT and RNA were compared. RESULTS: A total of 77 patients (mean age = 61.8 ± 12.2 years and 58 men) were analyzed. The mean LVEF measured by CT and RNA were 41.9 ± 15.2% and 39.4 ± 13.9%, respectively, (P = 0.154) with a good correlation (r = 0.863). Bland-Altman plot revealed a good agreement between the CT and RNA LVEF (mean difference of -2.4). There was good agreement between CT LVEF and RNA for identifying patients with LVEF ≤30% (kappa = 0.693) and LVEF ≥50% (kappa = 0.749). The mean dose estimated effective dose for CT and RNA were 4.7 ± 1.6 and 9.5 ± 1.0 mSv, respectively. The mean CT LVEF imaging duration (4:32 ± 3:05 minutes) was significantly shorter than the RNA image acquisition time (9:05 ± 2:36 minutes; p < 0.001). CONCLUSION: The results of our study suggest that low-dose CT LVEF protocol is feasible, accurate, and fast while delivering a lower radiation dose than traditional RNA.

Utilization of cardiac computed tomography angiography and outpatient invasive coronary angiography in Ontario, Canada.

BACKGROUND: Cardiac computed tomography angiography (coronary CTA) has emerged as a non-invasive method of diagnosing coronary artery disease. The extent of utilization and uptake of this technology since initiation of its funding by the government of Ontario is unknown. OBJECTIVES: The aim of our study was to examine coronary CTA utilization and the rates of elective invasive coronary angiography and revascularization before and after funding initiation. METHODS: We studied all coronary CTAs performed on adults in Ontario after initiation of funding. We also used an interrupted time series analysis to compare the average monthly rates of invasive angiography and revascularization before and after initiation of funding. RESULTS: There was an initial steep increase in age-and sex-standardized rates of coronary CTA from 5.0 to 11.4/100,000 over the first two quarters after funding initiation. Afterwards, there was a gradual increase in utilization from 11.4 to 17.1/100,000 over two subsequent calendar years. There was a significant reduction in both the mean monthly outpatient invasive coronary angiography (from 20.7 to 19.9 per 100,000 (p = 0.0004)) and revascularization (from 4.9 to 4.4 per 100,000 (p < 0.0001)) rates in the three years following introduction of the coronary CTA billing code as compared to the three prior to its introduction. CONCLUSIONS: Since the introduction of coronary CTA funding in Ontario, there has been a steady and controlled increase in its utilization. The increasing use of coronary CTA was associated with a reduction in both the rates of invasive angiography and revascularization.

Medical history for prognostic risk assessment and diagnosis of stable patients with suspected coronary artery disease.

OBJECTIVE: To develop a clinical cardiac risk algorithm for stable patients with suspected coronary artery disease based upon angina typicality and coronary artery disease risk factors. METHODS: Between 2004 and 2011, 14,004 adults with suspected coronary artery disease referred for cardiac imaging were followed: 1) 9093 patients for coronary computed tomography angiography (CCTA) followed for 2.0 years (CCTA-1); 2) 2132 patients for CCTA followed for 1.6 years (CCTA-2); and 3) 2779 patients for exercise myocardial perfusion scintigraphy (MPS) followed for 5.0 years. A best-fit model from CCTA-1 for prediction of death or myocardial infarction was developed, with integer values proportional to regression coefficients. Discrimination was assessed using C-statistic. The validated model was tested for estimation of the likelihood of obstructive coronary artery disease, defined as ≥50% stenosis, as compared with the method of Diamond and Forrester. Primary outcomes included all-cause mortality and nonfatal myocardial infarction. Secondary outcomes included prevalent angiographically obstructive coronary artery disease. RESULTS: In CCTA-1, best-fit model discriminated individuals at risk of death or myocardial infarction (C-statistic 0.76). The integer model ranged from 3 to 13, corresponding to 3-year death risk or myocardial infarction of 0.25% to 53.8%. When applied to CCTA-2 and MPS cohorts, the model demonstrated C-statistics of 0.71 and 0.77, respectively. Both best-fit (C = 0.76; 95% confidence interval [CI], 0.746-0.771) and integer models (C = 0.71; 95% CI, 0.693-0.719) performed better than Diamond and Forrester (C = 0.64; 95% CI, 0.628-0.659) for estimating obstructive coronary artery disease. CONCLUSIONS: For stable symptomatic patients with suspected coronary artery disease, we developed a history-based method for prediction of death and obstructive coronary artery disease.

Impact of SPECT myocardial perfusion imaging on cardiac care.

Single photon emission computed tomography myocardial perfusion imaging is a powerful modality for the assessment of coronary artery disease. It is useful in the diagnosis of CAD, prognostication of CAD and the determination of viability. It acts as guide for therapy and has the ability to assess effectiveness of therapy. The use of SPECT myocardial perfusion imaging has also been shown to be cost-effective compared to other modalities in cardiology.

Clinical interpretation standards and quality assurance for the multicenter PET/CT trial rubidium-ARMI.

UNLABELLED: Rubidium-ARMI ((82)Rb as an Alternative Radiopharmaceutical for Myocardial Imaging) is a multicenter trial to evaluate the accuracy, outcomes, and cost-effectiveness of low-dose (82)Rb perfusion imaging using 3-dimensional (3D) PET/CT technology. Standardized imaging protocols are essential to ensure consistent interpretation. METHODS: Cardiac phantom qualifying scans were obtained at 7 recruiting centers. Low-dose (10 MBq/kg) rest and pharmacologic stress (82)Rb PET scans were obtained in 25 patients at each site. Summed stress scores, summed rest scores, and summed difference scores (SSS, SRS, and SDS [respectively] = SSS-SRS) were evaluated using 17-segment visual interpretation with a discretized color map. All scans were coread at the core lab (University of Ottawa Heart Institute) to assess agreement of scoring, clinical diagnosis, and image quality. Scoring differences greater than 3 underwent a third review to improve consensus. Scoring agreement was evaluated with intraclass correlation coefficient (ICC-r), concordance of clinical interpretation, and image quality using κ coefficient and percentage agreement. Patient (99m)Tc and (201)Tl SPECT scans (n = 25) from 2 centers were analyzed similarly for comparison to (82)Rb. RESULTS: Qualifying scores of SSS = 2, SDS = 2, were achieved uniformly at all imaging sites on 9 different 3D PET/CT scanners. Patient scores showed good agreement between core and recruiting sites: ICC-r = 0.92, 0.77 for SSS, SDS. Eighty-five and eighty-seven percent of SSS and SDS scores, respectively, had site-core differences of 3 or less. After consensus review, scoring agreement improved to ICC-r = 0.97, 0.96 for SSS, SDS (P < 0.05). The agreement of normal versus abnormal (SSS ≥ 4) and nonischemic versus ischemic (SDS ≥ 2) studies was excellent: ICC-r = 0.90 and 0.88. Overall interpretation showed excellent agreement, with a κ = 0.94. Image quality was perceived differently by the site versus core reviewers (90% vs. 76% good or better; P < 0.05). By comparison, scoring agreement of the SPECT scans was ICC-r = 0.82, 0.72 for SSS, SDS. Seventy-six and eighty-eight percent of SSS and SDS scores, respectively, had site-core differences of 3 or less. Consensus review again improved scoring agreement to ICC-r = 0.97, 0.90 for SSS, SDS (P < 0.05). CONCLUSION: (82)Rb myocardial perfusion imaging protocols were implemented with highly repeatable interpretation in centers using 3D PET/CT technology, through an effective standardization and quality assurance program. Site scoring of (82)Rb PET myocardial perfusion imaging scans was found to be in good agreement with core lab standards, suggesting that the data from these centers may be combined for analysis of the rubidium-ARMI endpoints.

Routine versus selective cardiac magnetic resonance in non-ischemic heart failure - OUTSMART-HF: study protocol for a randomized controlled trial (IMAGE-HF (heart failure) project 1-B).

BACKGROUND: Imaging has become a routine part of heart failure (HF) investigation. Echocardiography is a first-line test in HF given its availability and it provides valuable diagnostic and prognostic information. Cardiac magnetic resonance (CMR) is an emerging clinical tool in the management of patients with non-ischemic heart failure. Current ACC/AHA/CCS/ESC guidelines advocate its role in the detection of a variety of cardiomyopathies but there is a paucity of high quality evidence to support these recommendations.The primary objective of this study is to compare the diagnostic yield of routine cardiac magnetic resonance versus standard care (that is, echocardiography with only selective use of CMR) in patients with non-ischemic heart failure. The primary hypothesisis that the routine use of CMR will lead to a more specific diagnostic characterization of the underlying etiology of non-ischemic heart failure. This will lead to a reduction in the non-specific diagnoses of idiopathic dilated cardiomyopathy and HF with preserved ejection fraction. DESIGN: Tertiary care sites in Canada and Finland, with dedicated HF and CMR programs, will randomize consecutive patients with new or deteriorating HF to routine CMR or selective CMR. All patients will undergo a standard clinical echocardiogram and the interpreter will assign the most likely HF etiology. Those undergoing CMR will also have a standard examination and will be assigned a HF etiology based upon the findings. The treating physician's impression about non-ischemic HF etiology will be collected following all baseline testing (including echo ± CMR). Patients will be followed annually for 4 years to ascertain clinical outcomes, quality of life and cost. The expected outcome is that the routine CMR arm will have a significantly higher rate of infiltrative, inflammatory, hypertrophic, ischemic and 'other' cardiomyopathy than the selective CMR group. DISCUSSION: This study will be the first multicenter randomized, controlled trial evaluating the role of CMR in non-ischemic HF. Non-ischemic HF patients will be randomized to routine CMR in order to determine whether there are any gains over management strategies employing selective CMR utilization. The insight gained from this study should improve appropriate CMR use in HF. TRIAL REGISTRATION: NCT01281384.

Integrating anatomical and functional imaging for the assessment of coronary artery disease.

Coronary artery disease (CAD) is a leading cause of morbidity and mortality. Invasive cardiac angiography with fractional flow reserve measurement allows for the anatomical and functional assessment of CAD. Given the invasive nature of invasive cardiac angiography and the risks of procedure-related complications, research has focused upon noninvasive methods for anatomical and functional measures of CAD. As such, there is growing interest in the development of hybrid imaging because it may provide incremental diagnostic information over each imaging modality alone. We will provide an overview of the evidence to date on the anatomical and functional stratification of CAD and current hybrid techniques.

Cost-effectiveness of 64-slice CT angiography compared to conventional coronary angiography based on a coverage with evidence development study in Ontario.

UNLABELLED: Conventional coronary angiography (CCA) is the standard diagnostic for coronary artery disease (CAD), but multi-detector computed tomography coronary angiography (CTCA) is a non-invasive alternative. METHODS: A multi-center coverage with evidence development study was undertaken and combined with an economic model to estimate the cost-effectiveness of CTCA followed by CCA vs CCA alone. Alternative assumptions were tested in patient scenario and sensitivity analyses. RESULTS: CCA was found to dominate CTCA, however, CTCA was relatively more cost-effective in females, in advancing age, in patients with lower pre-test probabilities of CAD, the higher the sensitivity of CTCA and the lower the probability of undergoing a confirmatory CCA following a positive CTCA. CONCLUSIONS: RESULTS were very sensitive to alternative patient populations and modeling assumptions. Careful consideration of patient characteristics, procedures to improve the diagnostic yield of CTCA and selective use of CCA following CTCA will impact whether CTCA is cost-effective or dominates CCA.

Anatomic versus physiologic assessment of coronary artery disease. Role of coronary flow reserve, fractional flow reserve, and positron emission tomography imaging in revascularization decision-making.

Angiographic severity of coronary artery stenosis has historically been the primary guide to revascularization or medical management of coronary artery disease. However, physiologic severity defined by coronary pressure and/or flow has resurged into clinical prominence as a potential, fundamental change from anatomically to physiologically guided management. This review addresses clinical coronary physiology-pressure and flow-as clinical tools for treating patients. We clarify the basic concepts that hold true for whatever technology measures coronary physiology directly and reliably, here focusing on positron emission tomography and its interplay with intracoronary measurements.

Lessons from the Tc-99m shortage: implications of substituting Tl-201 for Tc-99m single-photon emission computed tomography.

BACKGROUND: In 2009, the Chalk River nuclear reactor closed for repairs that led to a critical shortage of technetium-99m (Tc-99m). Several centers used thallium-201 (Tl-201) as an alternative radiotracer for myocardial perfusion imaging. Because Tl-201 is considered by many as a suboptimal radiotracer, we sought to understand the impact of using Tl-201 (during the Tc-99m shortage) on downstream resource utilization. METHODS AND RESULTS: We performed a retrospective study at the Ottawa Heart Institute of 7402 patients (60% men; mean age, 62.6 ± 11.8 years), patients were referred for myocardial perfusion imaging between May 2008 and January 2011 (PRE_Tc-99m [2938 patients]), during (DURING_Tl-201 [2959 patients]), and after (POST_Tc-99m [1505 patients]) the Tc-99m shortage. Patients were followed for 6 months after their index myocardial perfusion imaging to determine subsequent rates of cardiac catheterization or noninvasive imaging. More downstream testing was seen in the Tl-201 cohort (639 [21.4%] patients) than the Tc-99m cohort (537 [12.1%] patients; P<0.001). After adjustment using propensity scores, differences in downstream referral rates were maintained. The downstream investigations resulted in an estimated increase in per-patient costs ($165.22; 95% confidence interval, 153.00-177.42) in the DURING_Tl-201 cohort compared with the Tc-99m cohort ($90.97; 95% confidence interval, 83.42-98.90; P<0.001). As well, the mean effective radiation dose per-patient was higher in DURING_Tl-201 (23.57 mSv; 95% confidence interval, 23.16-23.96) than in Tc-99m (12.92 mSv; 95% confidence interval, 12.55-13.40; P<0.001). CONCLUSIONS: In this single-center study, the use of Tl-201 during the Tc-99m shortage was associated with an increase in downstream testing, cost, and patient radiation exposure, but these findings may not be generalizable to other centers. Although Tl-201 provided a short-term solution to the unexpected Tc-99m shortage, long-term cost-effective solutions should be areas of future study.

CT vs SPECT: CT is the first-line test for the diagnosis and prognosis of stable coronary artery disease.

Non-invasive cardiac imaging is pivotal in the diagnosis and prognosis of patients with stable CAD. Nuclear SPECT, PET, stress echocardiography and more recently cardiac magnetic resonance imaging have been utilized with excellent diagnostic accuracy. However, along with their inherent individual limitations, most modalities detect ischemia but lack the ability to define coronary anatomy or evaluate for subclinical atherosclerosis. A modality that not only accurately diagnoses obstructive CAD and also facilitates early identification of non-obstructive CAD may be of interest because it may allow for earlier aggressive risk factor modification and primary prevention. Cardiac computerized tomographic angiography (CCTA) has the potential to accurately detect or exclude luminal stenosis, as well as identify and quantify subclinical atherosclerosis in the absence if luminal narrowing. However CCTA, being a relatively a new modality, has less supporting evidence when compared to more mature modalities such as SPECT. Therefore, the question that begs to be addressed is whether CCTA can be utilized as a first line test in establishing the diagnosis and prognosis of CAD.

Individual patient data meta-analysis for the clinical assessment of coronary computed tomography angiography: protocol of the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT).

BACKGROUND: Coronary computed tomography angiography has become the foremost noninvasive imaging modality of the coronary arteries and is used as an alternative to the reference standard, conventional coronary angiography, for direct visualization and detection of coronary artery stenoses in patients with suspected coronary artery disease. Nevertheless, there is considerable debate regarding the optimal target population to maximize clinical performance and patient benefit. The most obvious indication for noninvasive coronary computed tomography angiography in patients with suspected coronary artery disease would be to reliably exclude significant stenosis and, thus, avoid unnecessary invasive conventional coronary angiography. To do this, a test should have, at clinically appropriate pretest likelihoods, minimal false-negative outcomes resulting in a high negative predictive value. However, little is known about the influence of patient characteristics on the clinical predictive values of coronary computed tomography angiography. Previous regular systematic reviews and meta-analyses had to rely on limited summary patient cohort data offered by primary studies. Performing an individual patient data meta-analysis will enable a much more detailed and powerful analysis and thus increase representativeness and generalizability of the results. The individual patient data meta-analysis is registered with the PROSPERO database (CoMe-CCT, CRD42012002780). METHODS/DESIGN: The analysis will include individual patient data from published and unpublished prospective diagnostic accuracy studies comparing coronary computed tomography angiography with conventional coronary angiography. These studies will be identified performing a systematic search in several electronic databases. Corresponding authors will be contacted and asked to provide obligatory and additional data. Risk factors, previous test results and symptoms of individual patients will be used to estimate the pretest likelihood of coronary artery disease. A bivariate random-effects model will be used to calculate pooled mean negative and positive predictive values as well as sensitivity and specificity. The primary outcome of interest will be positive and negative predictive values of coronary computed tomography angiography for the presence of coronary artery disease as a function of pretest likelihood of coronary artery disease, analyzed by meta-regression. As a secondary endpoint, factors that may influence the diagnostic performance and clinical value of computed tomography, such as heart rate and body mass index of patients, number of detector rows, and administration of beta blockade and nitroglycerin, will be investigated by integrating them as further covariates into the bivariate random-effects model. DISCUSSION: This collaborative individual patient data meta-analysis should provide answers to the pivotal question of which patients benefit most from noninvasive coronary computed tomography angiography and thus help to adequately select the right patients for this test.