Genders, T.S.S.

Diagnostic Imaging Strategies for Patients with Suspected Coronary Artery Disease (Doctoral Thesis)

2012-06-29T00:00:00Z

In this thesis, our aim was to determine and optimize the diagnostic work-up for patients who are suspected of having coronary artery disease (CAD). We showed that the diagnostic performance of stress perfusion magnetic resonance imaging (MRI) compares favorably to the diagnostic performance of single-photon emission computed tomography (SPECT). If both tests can be performed in a patient, then stress perfusion MRI should be the preferred test, even more so because it does not involve exposure to radiation. We demonstrated that the coronary CT calcium score has predictive value beyond existing cardiovascular risk factors for diagnosing obstructive CAD in patients with chest pain. The CT coronary calcium score could be considered as an initial triage test in patients with a low pre-test probability of CAD, preventing (unnecessary) further work-up if the score is zero, and justifying further testing when coronary calcium is present. The optimal diagnostic strategy depends on the pre-test probability of CAD, which is traditionally estimated based on the Diamond & Forrester method or the Duke Clinical Score. We demonstrated that these prediction rules systematically overestimate the probability of CAD and we updated the models based on contemporary data. An online probability calculator was developed that provides systematically lower (but more accurate) estimates of the pre-test probability. Although we did not study the clinical impact of implementing our new prediction model, a more accurate estimate of the pre-test probability is likely to lead to better decisions regarding further testing and it could potentially reduce costs since less high probabilities are predicted which in turn may prevent unnecessary diagnostic work-up. Lastly, we evaluated the long term effectiveness and costs of coronary CT angiography in various different settings and for various countries. In the Dutch setting, coronary CT angiography was found to be cost-effective as triage test prior to catheter-based coronary angiography (CAG) if the pre-test probability was below 44% in men and below 37% in women. CT coronary calcium scoring with or without subsequent coronary CT angiography as initial strategy for patients presenting with stable chest pain was less expensive and equally effective compared to standard-of-care. Finally, we showed that a strategy using coronary CT angiography, if positive followed by cardiac magnetic resonance imaging (CMR) was cost-effective compared to strategies with coronary CT angiography and CMR alone, for the United States, the United Kingdom, as well as the Netherlands. All-in-all, our updated prediction models combined with the results from our decision models and cost-effectiveness analyses provide a practical framework for efficient implementation of diagnostic imaging tests, in particular for the CT coronary calcium score and coronary CT angiography.

Stable angina pectoris: Head-to-head comparison of prognostic value of cardiac CT and exercise testing (Article)

2011-11-01T00:00:00Z

Purpose: 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). Materials and 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 χ2, 37.7 vs 13.7; P<.001), whereas coronary calcium scores did not have further incremental value (global χ2, 38.2 vs 37.7; P = .40). Conclusion: CT angiography findings are a strong predictor of future adverse events, showing incremental value over clinical predictors, stress testing, and coronary calcium scores.

Prognostic value of cardiac computed tomography angiography (Article)

2011-06-21T00:00:00Z

A clinical prediction rule for the diagnosis of coronary artery disease: Validation, updating, and extension (Article)

2011-06-01T00:00:00Z

AimsThe aim was to validate, update, and extend the DiamondForrester model for estimating the probability of obstructive coronary artery disease (CAD) in a contemporary cohort. Methods and resultsProspectively collected data from 14 hospitals on patients with chest pain without a history of CAD and referred for conventional coronary angiography (CCA) were used. Primary outcome was obstructive CAD, defined as <50 stenosis in one or more vessels on CCA. The validity of the DiamondForrester model was assessed using calibration plots, calibration-in-the-large, and recalibration in logistic regression. The model was subsequently updated and extended by revising the predictive value of age, sex, and type of chest pain. Diagnostic performance was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) and reclassification was determined. We included 2260 patients, of whom 1319 had obstructive CAD on CCA. Validation demonstrated an overestimation of the CAD probability, especially in women. The updated and extended models demonstrated a c-statistic of 0.79 (95 CI 0.770.81) and 0.82 (95 CI 0.800.84), respectively. Sixteen per cent of men and 64 of women were correctly reclassified. The predicted probability of obstructive CAD ranged from 10 for 50-year-old females with non-specific chest pain to 91 for 80-year-old males with typical chest pain. Predictions varied across hospitals due to differences in disease prevalence. Conclusion Our results suggest that the DiamondForrester model overestimates the probability of CAD especially in women. We updated the predictive effects of age, sex, type of chest pain, and hospital setting which improved model performance and we extended it to include patients of 70 years and older.

Systematic review of guidelines on imaging of asymptomatic coronary artery disease (Article)

2011-04-05T00:00:00Z

Objectives: The purpose of this study was to critically appraise guidelines on imaging of asymptomatic coronary artery disease (CAD). Background: Various imaging tests exist to detect CAD in asymptomatic persons. Because randomized controlled trials are lacking, guidelines that address the use of CAD imaging tests may disagree. Methods: Guidelines in English published between January 1, 2003, and February 26, 2010, were retrieved using MEDLINE, Cumulative Index to Nursing and Allied Health Literature, the National Guideline Clearinghouse, the National Library for Health, the Canadian Medication Association Infobase, and the Guidelines International Network International Guideline Library. Guidelines developed by national and international medical societies from Western countries, containing recommendations on imaging of asymptomatic CAD were included. Rigor of development was scored by 2 independent reviewers using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. One reviewer performed full extraction of recommendations, which was checked by a second reviewer. Results: Of 2,415 titles identified, 14 guidelines met our inclusion criteria. Eleven of 14 guidelines reported relationship with industry. The AGREE scores varied across guidelines from 21% to 93%. Two guidelines considered cost effectiveness. Eight guidelines recommended against or found insufficient evidence for testing of asymptomatic CAD. The other 6 guidelines recommended imaging patients at intermediate or high CAD risk based on the Framingham risk score, and 5 considered computed tomography calcium scoring useful for this purpose. Conclusions: Guidelines on risk assessment by imaging of asymptomatic CAD contain conflicting recommendations. More research, including randomized controlled trials, evaluating the impact of imaging on clinical outcomes and costs is needed.

Incremental value of the CT coronary calcium score for the prediction of coronary artery disease (Article)

2010-10-01T00:00:00Z

Objectives:: To validate published prediction models for the presence of obstructive coronary artery disease (CAD) in patients with new onset stable typical or atypical angina pectoris and to assess the incremental value of the CT coronary calcium score (CTCS). Methods:: We searched the literature for clinical prediction rules for the diagnosis of obstructive CAD, defined as≥50% stenosis in at least one vessel on conventional coronary angiography. Significant variables were re-analysed in our dataset of 254 patients with logistic regression. CTCS was subsequently included in the models. The area under the receiver operating characteristic curve (AUC) was calculated to assess diagnostic performance. Results:: Re-analysing the variables used by Diamond & Forrester yielded an AUC of 0.798, which increased to 0.890 by adding CTCS. For Pryor, Morise 1994, Morise 1997 and Shaw the AUC increased from 0.838 to 0.901, 0.831 to 0.899, 0.840 to 0.898 and 0.833 to 0.899. CTCS significantly improved model performance in each model. Conclusions:: Validation demonstrated good diagnostic performance across all models. CTCS improves the prediction of the presence of obstructive CAD, independent of clinical predictors, and should be considered in its diagnostic work-up. © 2010 The Author(s).

Suspected carotid artery stenosis: Cost-effectiveness of CT angiography in work-up of patients with recent TIA or minor ischemic stroke (Article)

2010-08-01T00:00:00Z

Purpose: To assess the effectiveness and cost-effectiveness of state-of-the-art noninvasive diagnostic imaging strategies in patients with a transient ischemic attack (TIA) or minor stroke who are suspected of having carotid artery stenosis (CAS). Materials and Methods: All prospectively evaluated patients provided informed consent, and the local ethics committee approved this study. Diagnostic performance, treatment, long-term events, quality of life, and costs resulting from strategies employing duplex ultrasonography (US), computed tomographic (CT) angiography, contrast material-enhanced magnetic resonance (MR) angiography, and combinations of these modalities were modeled in a decision tree and Markov model. Data sources included a prospective diagnostic cohort study, a meta-analysis, and a review of the literature. Outcomes were costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios, and net health benefits (QALY-equivalents), with a willingness-to-pay threshold of €50 000 per QALY and a societal perspective. The strategy with the highest net health benefit was considered the most cost effective. Extensive one-way, two-way, and probabilistic sensitivity analyses to explore the effect of varying parameter values were performed. The reference case analysis assumed that patients underwent surgery 2-4 weeks after the first symptoms, and the effect of earlier intervention was explored. Results: The reference case analysis showed that duplex US combined with CT angiography and surgery for 70%-99% stenoses was the most cost-effective strategy, with a net health benefit of 13.587 and 15.542 QALY-equivalents in men and women, respectively. In men, the CT angiography strategy with a 70%-99% cutoff yielded slightly more QALYs, at an incremental cost of €71 419 per QALY, compared with duplex US combined with CT angiography. In patients with a high-risk profile, in patients with a high prior probability of disease, and when patients could be treated within 2 weeks after the first symptoms, the CT angiography strategy with surgery for 50%-99% stenoses was the most cost-effective strategy. Conclusion: In diagnosing CAS, duplex US should be the initial test, and, if its results are positive, CT angiography should be performed; patients with 70%-99% stenoses should then undergo carotid endarterectomy. In patients with a high-risk profile, a high probability of CAS, or who can undergo surgery without delay, immediate CT angiography and surgery for 50%-99% stenoses is indicated.

CT coronary angiography in patients suspected of having coronary artery disease: Decision making from various perspectives in the face of uncertainty (Article)

2009-12-01T00:00:00Z

Purpose: To determine the cost-effectiveness of computed tomographic (CT) coronary angiography as a triage test, performed prior to conventional coronary angiography, by using a Markov model. Materials and Methods: A Markov model was used to analyze the cost-effectiveness of CT coronary angiography performed as a triage test prior to conventional coronary angiography from the perspective of the patient, physician, hospital, health care system, and society by using recommendations from the United Kingdom, the United States, and the Netherlands for cost-effectiveness analyses. For CT coronary angiography, a range of sensitivities (79%-100%) and specificities (63%-94%) were used to help diagnose significant coronary artery disease (CAD). Optimization criteria (ie, outcomes considered) were: revised posttest probability of CAD, life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Extensive sensitivity analysis was performed. Results: For a prior probability of CAD of less than 40%, the probability of CAD after CT coronary angiography with negative results was less than 1%. The Markov model calculations from the patient/physician perspective suggest that CT coronary angiography maximizes life-years respectively in 60-year-old men and women at a prior probability of less than 38% and 24% and maximizes QALYs at a prior probability of less than 17% and 11%. From the hospital/health care perspective, CT coronary angiography helps reduce health care and direct nonhealth care-related costs (according to UK/U.S. recommendations), regardless of prior probability, and lowers all costs, including production losses (Netherlands recommendations) at a prior probability of less than 87%-92%. Analysis performed from a societal perspective by using a willingness-topay threshold level of €80 000/QALY suggests that CT coronary angiography is cost-effective when the prior probability is lower than 44% and 37% in men and women, respectively. Sensitivity analyses showed that results changed across the reported range of sensitivity of CT coronary angiography. Conclusion: The optimal diagnostic work-up depends on the optimization criterion, prior probability of CAD, and the diagnostic performance of CT coronary angiography.