Low Likelihood Of Coronary Artery Disease Research Articles

Performance of the American Heart Association/American College of Cardiology Guideline-Recommended Pretest Probability Model for the Diagnosis of Obstructive Coronary Artery Disease.

Background Substantial differences exist between different guideline-recommended pretest probability (PTP) models for the detection of obstructive coronary artery disease (CAD). This study was performed to study the performance of the 2021 American Heart Association/American College of Cardiology (AHA/ACC) guideline-recommended PTP (AHA/ACC-PTP) model in assessing the likelihood of obstructive CAD compared with previously proposed models. Methods and Results Symptomatic patients (N=50 561) referred for coronary computed tomography angiography were included. The reference standard was invasive coronary angiography with optional fractional flow reserve measurements. The AHA/ACC-PTP values based on sex and age were calculated and compared with the 2019 European Society of Cardiology guideline PTP values based on sex, age, and symptoms as well as the risk factor-weighted clinical likelihood values based on sex, age, symptoms, and risk factors. The AHA/ACC-PTP maximum values overestimated by a factor of 2.6 the actual prevalence of CAD. Compared with the AHA/ACC-PTP model (area under the receiver-operating curve, 71.5 [95% CI, 70.7-72.2]), inclusion of typicality of symptoms in the European Society of Cardiology guideline PTP improved discrimination of CAD (area under the receiver-operating curve, 75.5 [95% CI, 74.7-76.3]). Inclusion of both symptoms and risk factors in the risk factor-weighted clinical likelihood model further improved discrimination (area under the receiver-operating curve, 77.7 [95% CI, 77.0-78.5]). The proportion of patients classified as very low PTP was lower using the AHA/ACC-PTP (5%) compared with the European Society of Cardiology guideline PTP (19%) and the risk factor-weighted clinical likelihood (49%) models. Conclusions The new AHA/ACC-PTP model overestimates the prevalence of obstructive CAD substantially if type of symptoms and risk factors are not taken into account. Inclusion of both symptoms and risk factors improves model performance and identifies more patients with very low likelihood of CAD in whom further testing can be deferred.

Mitigating bias in deep learning for diagnosis of coronary artery disease from myocardial perfusion SPECT images.

Artificial intelligence (AI) has high diagnostic accuracy for coronary artery disease (CAD) from myocardial perfusion imaging (MPI). However, when trained using high-risk populations (such as patients with correlating invasive testing), the disease probability can be overestimated due to selection bias. We evaluated different strategies for training AI models to improve the calibration (accurate estimate of disease probability), using external testing. Deep learning was trained using 828 patients from 3 sites, with MPI and invasive angiography within 6months. Perfusion was assessed using upright (U-TPD) and supine total perfusion deficit (S-TPD). AI training without data augmentation (model 1) was compared to training with augmentation (increased sampling) of patients without obstructive CAD (model 2), and patients without CAD and TPD < 2% (model 3). All models were tested in an external population of patients with invasive angiography within 6months (n = 332) or low likelihood of CAD (n = 179). Model 3 achieved the best calibration (Brier score 0.104 vs 0.121, p < 0.01). Improvement in calibration was particularly evident in women (Brier score 0.084 vs 0.124, p < 0.01). In external testing (n = 511), the area under the receiver operating characteristic curve (AUC) was higher for model 3 (0.930), compared to U-TPD (AUC 0.897) and S-TPD (AUC 0.900, p < 0.01 for both). Training AI models with augmentation of low-risk patients can improve calibration of AI models developed to identify patients with CAD, allowing more accurate assignment of disease probability. This is particularly important in lower-risk populations and in women, where overestimation of disease probability could significantly influence down-stream patient management.

An acoustic based risk score in addition to pre-test probability estimation for coronary artery disease improves risk classification in patients with suspected coronary artery disease

Abstract Background The 2021 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline for Evaluation and Diagnosis of Chest Pain introduced a new pre-test probability (PTP)-table for risk stratification of patients with symptoms suggestive of coronary artery disease (CAD). The CAD-score, an acoustic-based risk score for obstructive CAD, has previously shown good rule out capability in patients with suggested CAD when added to PTP. Purpose To investigate the potential of the acoustic CAD-score to 1) reclassify patients from intermediate-high to low PTP, and 2) improve risk-stratification in patients with low PTP, when added to the 2021 AHA/ACC PTP. Methods This is a retrospective study of patients with successfully obtained CAD-score from The Danish study of Non-Invasive testing in Coronary artery Disease 1 (Dan-NICAD 1) of patients without known CAD referred for coronary computed tomography angiography with angina pectoris. Patients with suspected obstructive CAD underwent invasive angiography. CAD-score was obtained with a non-invasive acoustic device analysing heart sounds based on CAD-related turbulence. CAD-score≤20 indicated low probability of CAD. PTP was calculated from sex, age, and angina symptoms according to current AHA/ACC Guidelines. Low likelihood of CAD was defined as PTP≤15%, and intermediate-high likelihood as PTP&amp;gt;15%. Hemodynamic obstructive CAD was defined as visual luminal diameter stenosis &amp;gt;90% on angiography or FFR&amp;lt;0.80%. Results Among the 1475 included patients (52.3% women, median age 57 years IQR [50–64[), 36.4% were categorized as low likelihood of CAD (PTP≤15%), and 9.8% of patients had obstructive CAD. Compared to patients with PTP≤15%, patients with PTP&amp;gt;15%, were older, more often hypertensive (49.8% vs. 35.5%), had a higher median CAD-score (28 [22–38] vs. 16 [12–22]), and had more obstructive CAD (12.4% vs. 5.2%). CAD-score reclassified 17.6% of patients with intermediate-high likelihood to a low likelihood of CAD and decreased the post-test probability of obstructive CAD from 5.2% to 4.7%. Subgroup analyses showed reclassification was greater in men, patients with PTP ≤25%, age &amp;lt;70 years or no hypertension. In the 432 patients with PTP&amp;gt;15%, age&amp;lt;70 and no hypertension, 35.4% were reclassified to low likelihood, whereas only 2.4% of patients with PTP&amp;gt;15%, age≥70 years or hypertension were ruled out by CAD-score ≤20. In patients with low PTP≤15%, CAD-score≤20 risk-stratified 361 (67.2%) patients to very low and 176 (32.8%) to an intermediate-low likelihood of CAD, but the post-test probabilities of CAD in both subgroups were still below the cut-off of 15 (3.6% vs. 8.5%). Conclusion Adding an acoustic-based CAD-score to the AHA/ACC PTP could potentially reduce the need for further diagnostic testing by 17.6% in patients with intermediate-high likelihood of CAD and in subgroups a reduction of 35% can be achieved. Use of CAD-score in low-likelihood patients only moderately improves risk classification. Funding Acknowledgement Type of funding sources: None.

Sex Differences in Computed Tomographic Angiography in Patients with Low and Intermediate Pretest Probability of Coronary Artery Disease

Background: Multi-slice computed tomography (MSCT) coronary angiography has become one of the hot spots in cardiovascular imaging technology. Many of the sex-based research have shown that women have different pathogenesis, clinical presentation and complication related to coronary artery disease (CAD) as compared to the males. The aim of this study investigated the relationship between gender and coronary artery calcium (CAC) in patients with chest discomfort with low and intermediate pretest probability of CAD who underwent Coronary computed tomography angiography (CCTA) and referrals by gender for subsequent invasive coronary angiography and revascularization.&#x0D; Methods: This prospective cohort study included 200 patients suspected to have coronary artery disease, negative or equivocal stress tests, with no prior known coronary artery disease (CAD), intermediate pretest probability for CAD according to the scoring method of (15-65 points), and Low likelihood for CAD (&lt; 15 points). Patients were divided into two groups according to gender and were followed up. All patients underwent Full history taking, full clinical examination, routine laboratory investigation, resting and exercise ECG, echocardiography, CT coronary angiography and invasive Coronary angiography.&#x0D; Results: Patients with mild calcium score level were significantly higher in no CAD group than CAD group (p &lt;0.001) and patients with high calcium score were significantly higher in CAD group than no CAD group (p &lt;0.001). In univariate regression analysis age, typical chest pain, obesity, coronary Ca score, and hyperlipidemia are independent predictors for CAD in females. In multivariate regression analysis, age, typical chest pain, hypertension, and coronary Ca score are predictors for CAD in males. Coronary calcium score is a good predicator for CAD (AUC =0.901, 95% CI =0.851-0.938, p value &lt;0.001). At cut off value &gt; 101, it has 70.97% sensitivity, 90.79% specificity, 92.6% PPV, and 65.7% NPV. Moreover, it is a good predicator for CAD in females (AUC =0.894, 95% CI =0.823 – 0.944, p value &lt;0.001). At cut off value &gt; 101, it has 60.71% sensitivity, 91.67% specificity, 87.2% PPV, and 71.4% NPV.&#x0D; Conclusions: In patients with chest discomfort with low and intermediate pretest probability of CAD who underwent CCTA and subsequent invasive coronary angiography and revascularization, female patients had lower age, hypertension, pretest probability score, calcium score, atypical angina, nonanginal chest pain and obstructive CAD but had higher BMI, typical angina than males’ group. In females, coronary calcium score is a good predicator for CAD. When its level exceeds 100, it has 60.71% sensitivity and 91.67% specificity. In addition, it was found that in females typical chest pain and coronary Ca score are predictors for CAD and in males, age, typical chest pain, hypertension, and coronary Ca score are predictors for CAD.

409 Not all ST elevation are myocardial infarction: a lesson learned from ‘spiked helmet sign’

Abstract Aims ST segment elevation is an electrocardiogram (ECG) finding first of all suggestive of acute coronary syndrome (ACS). However, there are other causes of ST segment elevation that seem to not have any relationship with coronary artery disease (CAD). One of these is the so-called ‘Spiked Helmet Sign’ (SHS), an ECG pattern characterized by upslope of ST segment before R wave onset that is reported to be found in critical illness and is associated with negative outcomes. Methods and results A 14-years-old boy came comatose (Glasgow Coma Scale = 4) to the Emergency Room after being run over by a car. He was immediately intubated and mechanically ventilated. Baseline ECG was reported to be normal, showing an incomplete right bundle branch block and a slightly prolonged QTc interval. CT-scan showed subarachnoid haemorrhage and multiple skull fractures requiring decompressive craniectomy. During hospitalization the patient developed marked hypotension complicated by rise of inflammation indexes and 12 lead ECG revealed new-onset of diffuse ST-segment elevation with spike-and-dome appearance mainly in lateral precordial leads, while lead II and V2 didn’t show any ST-segment alteration. Transthoracic echocardiogram was reported to be normal. Due to critical conditions and low likelihood of CAD, angiography wasn’t performed. The clinical course was worsened by occurrence of hyperkalaemia, acute kidney injury, and multiple episodes of ventricular tachycardia evolving in pulselessness electrical activity which required advanced life support. The patient subsequently died due to multi-organ failure, without the possibility of escalation therapy due to his status. SHS is an emerging ECG sign that is reported to be associated with critical conditions (mechanical ventilation, sepsis, bowel perforation) and in the majority of cases it is not related to CAD. It usually occurs in inferior leads (especially in case of abdominal disease) and in precordial leads (pneumothorax, aortic dissection, mechanical ventilation). Our patient had features consistent with previous cases reported in literature and, even if he experienced several episodes of cardiac arrest and blood exams revealed elevated values of cardiac troponin, the typical ECG pattern and the normal echocardiogram suggest SHS instead of ACS, avoiding unnecessary percutaneous coronary intervention. As reported in literature, even if in our case the appearance of this sign was associated with poor prognosis. Conclusions SHS mainly occurs in critically ill patients and is associated with death and poor outcomes. The potential pathophysiological mechanisms are still unclear. It is important to promptly recognize this pattern and differentiate between other causes of ST-segment elevation to select the appropriate therapy according to the setting. This is the first case-report among Italian hospitals of SHS.

Critical Appraisal Of A Clinical Risk Score To Avoid Coronary Computed Tomography In Patients With Calcium Score Of Zero

Introduction: Patients with a calcium score of zero have a low but non-negligible probability of obstructive coronary artery disease (CAD). Recently, a clinical score was proposed to identify a subset of patients with a calcium score of zero with very low likelihood of CAD, in whom coronary CT angiography (CCTA) could be safely withheld. The aim of this study was to assess the performance of this tool in a Portuguese cohort of patients undergoing CCTA for suspected CAD.

Creation and characterization of normal myocardial perfusion imaging databases using the IQ·SPECT system

BackgroundImage acquisition by short-time single-photon emission-computed tomography (SPECT) has been made feasible by IQ·SPECT. The aim of this study was to generate normal databases (NDBs) of thallium-201 (201Tl) myocardial perfusion imaging for IQ·SPECT, and characterize myocardial perfusion distribution. Methods and resultsWe retrospectively enrolled 159 patients with a low likelihood of cardiac diseases from four hospitals in Japan. All patients underwent short-time 201Tl myocardial perfusion IQ·SPECT with or without attenuation and scatter correction (ACSC) in either supine or prone position. The mean myocardial counts were calculated using 17-segment polar maps. Three NDBs were derived from supine and prone images as well as supine images with ACSC. Differences between the supine and prone positions were observed in the uncorrected sex-segregated NDBs in the mid-inferolateral counts (p ≤ 0.016 for males and p ≤ 0.002 for females). Differences between IQ·SPECT and conventional SPECT were also observed in the mid-anterior, inferolateral, and apical lateral counts (p ≤ 0.009 for males and p ≤ 0.003 for females). Apical low counts attributed to myocardial thinning were observed in the apical anterior and apex segments in the supine IQ·SPECT NDB with ACSC. ConclusionsThere were significant differences between uncorrected supine and prone NDBs, between uncorrected supine NDB and supine NDB with ACSC, and between uncorrected supine NDB and conventional SPECT NDB. Understanding the pattern of normal distribution in IQ-SPECT short-time acquisitions with and without ACSC will be helpful for interpretation of imaging findings in patients with coronary artery disease (CAD) or low likelihood of CAD and the NDBs will aid in quantitative analysis.

Stress thallium-201/rest technetium-99m sequential dual-isotope high-speed myocardial perfusion imaging validation versus invasive coronary angiography

BackgroundRecent advances in nuclear myocardial perfusion imaging (MPI) have made it possible to develop a dual-isotope protocol for high-speed acquisition with image quality and radiation delivery comparable to that obtained with conventional single isotope protocols. So far, no study has compared dual-isotope high-speed MPI to invasive coronary angiography (ICA) in a large cohort using a Cadmium-zinc-telluride SPECT system. MethodsOver a 1-year period (May 2011 to April 2012), 1366 patients underwent dual-isotope high-speed MPI. Patients with ICA within 3 months after dual-isotope high-speed MPI were included together with patients with a low likelihood of coronary artery disease (CAD) in order to assess normalcy rate. Global summed stress score (SSS) and summed rest score (SRS) were calculated, and ICA results were analyzed independently. The main end point was a patient-based assessment of the diagnostic performance of dual-isotope high-speed MPI in detecting or ruling out significant CAD (>70% reduction in lumen diameter). ResultsInclusion criteria were fulfilled for 214 patients (143 men; age 60 ± 14 years; ICA, n = 104; low likelihood for CAD, n = 110). An exercise stress test was performed in 62% of patients and a pharmacological stress test was performed with either dipyridamole (32%) or dobutamine (6%). Average examination duration was 22.4 ± 4.5 minutes. Mean SSS, SRS, and SDS were 8.0 ± 4.9, 3.1 ± 4.3, and 5.0 ± 3.2, respectively. Prevalence of angiographic CAD was 75%. ICA detected stenosis in the left main trunk, left anterior descending artery, left circumflex artery, and right coronary artery in 4, 33, 31, and 42 patients, respectively. Sensitivity of dual-isotope high-speed MPI was 94%, normalcy rate was 92%, and accuracy was 83% for detecting CAD. ConclusionDual-isotope high-speed MPI is reliable at detecting or ruling out CAD. NCT01785589

Quantitative high-efficiency cadmium-zinc-telluride SPECT with dedicated parallel-hole collimation system in obese patients: Results of a multi-center study

BackgroundObesity is a common source of artifact on conventional SPECT myocardial perfusion imaging (MPI). We evaluated image quality and diagnostic performance of high-efficiency (HE) cadmium-zinc-telluride parallel-hole SPECT MPI for coronary artery disease (CAD) in obese patients. Methods and Results118 consecutive obese patients at three centers (BMI 43.6 ± 8.9 kg·m−2, range 35-79.7 kg·m−2) had upright/supine HE-SPECT and invasive coronary angiography > 6 months (n = 67) or low likelihood of CAD (n = 51). Stress quantitative total perfusion deficit (TPD) for upright (U-TPD), supine (S-TPD), and combined acquisitions (C-TPD) was assessed. Image quality (IQ; 5 = excellent; < 3 nondiagnostic) was compared among BMI 35-39.9 (n = 58), 40-44.9 (n = 24) and ≥45 (n = 36) groups. ROC curve area for CAD detection (≥50% stenosis) for U-TPD, S-TPD, and C-TPD were 0.80, 0.80, and 0.87, respectively. Sensitivity/specificity was 82%/57% for U-TPD, 74%/71% for S-TPD, and 80%/82% for C-TPD. C-TPD had highest specificity (P = .02). C-TPD normalcy rate was higher than U-TPD (88% vs 75%, P = .02). Mean IQ was similar among BMI 35-39.9, 40-44.9 and ≥45 groups [4.6 vs 4.4 vs 4.5, respectively (P = .6)]. No patient had a nondiagnostic stress scan. ConclusionsIn obese patients, HE-SPECT MPI with dedicated parallel-hole collimation demonstrated high image quality, normalcy rate, and diagnostic accuracy for CAD by quantitative analysis of combined upright/supine acquisitions.

Are SPECT measurements of myocardial blood flow and flow reserve ready for clinical use?

SPECT myocardial perfusion imaging (MPI) well-documented diagnostic accuracy for detecting coronary artery disease (CAD) has promoted the widespread clinical use of this modality. Nevertheless, SPECT MPI’s success has been attained using the basic SPECT camera design which is over 50 years old [1], using the basic filtered backprojection reconstruction algorithm which is even older, dating to over 90 years ago [2], and using Tc-99m based perfusion agents with limited extraction fractions [3]. Moreover, although SPECT MPI is inherently a digital, quantitative technique, our clinical approach to quantify hypoperfusion has depended on a database approach where a patient’s left ventricular perfusion pattern is statistically compared to an expected normal perfusion pattern generated from patients with low likelihood of CAD [4–6]. In spite of the success of SPECT MPI using these established conventional approaches, recent innovations are poised to bring SPECT MPI to the next level. In a recent article in EJNMMI, Hsu et al. [7] report on the use of dynamic SPECT with a SPECT/CT camera, to measure absolute myocardial blood flow (MBF) and myocardial blood flow reserve (MBFR) in patients. The authors conclude that their flow quantitation method is a clinically effective approach to enhance CAD detection. Thus it is pertinent to ask: Are SPECT measurements of myocardial blood flow and flow reserve ready for clinical use?

Diagnostic role of coronary calcium scoring in the rapid access chest pain clinic: prospective evaluation of NICE guidance

Coronary artery calcium (CAC) imaging by unenhanced computed X-ray tomography (CT) is recommended as an initial diagnostic test for patients with stable chest pain symptoms but a low likelihood (10-29%) of underlying obstructive coronary artery disease (CAD) after clinical assessment. The recommendation has not previously been tested prospectively in a rapid access chest pain clinic (RACPC). We recruited 300 consecutive patients presenting with stable chest pain to the RACPC of three hospitals. All patients underwent CAC imaging, followed by invasive coronary angiography (ICA) in patients with CAC ≥ 1000 Agatston units (Au) and CT coronary angiography (CTCA) in those with CAC <1000. Patients with 50-70% stenosis on CTCA underwent myocardial perfusion scintigraphy (MPS) while those with ≥ 70% stenosis underwent ICA. Obstructive CAD was defined as ≥ 70% stenosis on ICA or the presence of inducible ischaemia on MPS. Patients were followed up clinically for a mean of 17 (SD 6) months. The mean patient age was 60.6 (SD 9.6) years and 48% were males. Obstructive CAD was found in 56 (19%) patients, of whom 42 (14%) underwent revascularization. CAC was zero in 131 (44%) patients, of whom two (1.5%) had obstructive CAD and one (0.8%) underwent revascularization. The sensitivity, specificity, negative predictive value, and positive predictive value of CAC ≥ 1 for detection of obstructive CAD were 96, 53, 32, and 98%, respectively. None of the 57 patients with low pre-test probability of CAD and zero CAC had obstructive CAD or suffered a cardiovascular event during the follow-up. Patients with stable chest pain symptoms but a low likelihood of CAD can safely be diagnosed as not having obstructive CAD in the absence of detectable coronary calcification by unenhanced CT. Patients with CAC >400 Au have a high prevalence of obstructive CAD and further investigation with ICA or functional imaging may be warranted rather than CTCA. These findings support NICE guidance for the investigation of stable chest pain. ClinicalTrials gov identifier: NCT01464203.

Diagnostic performance of low-dose rest/stress Tc-99m tetrofosmin myocardial perfusion SPECT using the 530c CZT camera: Quantitative vs visual analysis

BackgroundWe set out to develop normal databases and prospectively validate abnormality criteria for a low-dose Tc-99m tetrofosmin myocardial perfusion SPECT protocol using the 530c CZT camera. MethodsAll patients received 6 mCi rest/20 mCi stress doses of Tc-99m tetrofosmin. Rest and stress images were obtained over 7-9 and 5-7 minutes according to the chest size. Low-dose CT of the chest was obtained on a standalone CT scanner. Forty patients with very low likelihood (LLK) of coronary artery disease (CAD) were used to define the normal count distributions. The abnormality criteria were prospectively validated in 55 patients who had coronary angiography and in 40 patients with LLK of CAD. ResultsThe results for quantitative non-attenuation-corrected (AC) and AC analysis and visual analysis were as follows: sensitivity of 79%, 85%, and 92% (P = NS) and specificity of 44%, 75%, and 56% (P = NS), respectively. The normalcy rates for quantitative non-AC and AC analyses and visual analysis were 95%, 98%, and 98% (P = NS). ConclusionsWe have developed non-AC and AC normal databases for low-dose rest/stress Tc-99m tetrofosmin myocardial perfusion SPECT protocol using the 530c CZT camera. The per-patient diagnostic performance of quantitative analyses is not significantly different from visual analysis by an experienced reader.

The prognostic value of transient ischemic dilatation with otherwise normal SPECT myocardial perfusion imaging: A cautionary note in patients with diabetes and coronary artery disease

BackgroundThe prognostic implications of transient ischemic dilatation (TID) of the left ventricle with otherwise normal single-photon emission computed tomography myocardial perfusion imaging (MPI) remain controversial. Whether this finding may have prognostic implications only in high-risk populations, such as patients with diabetes or manifest coronary artery disease (CAD), is uncertain. MethodsWe conducted a prospective cohort study of 1,236 consecutive patients with normal 99mTc-sestamibi MPI, defined as normal perfusion (summed stress score = 0) and normal left ventricle volume and function. TID was defined as >2 standard deviations above the mean of patients with low likelihood of CAD. ResultsThe study subjects were followed for 27 ± 9 months. The 76 (6%) patients with TID had a greater rate of cardiac death or myocardial infarction (MI) [4 (5.3%) vs 11 (0.6%), P = .003] independent of covariates [hazard ratio = 6.4, P = .004]. This finding was entirely derived from the subgroup of 294 patients with diabetes or CAD [4 (13.3%) with TID vs 1 (0.4%) without TID, P = .001] independent of covariates. However, TID was not predictive of cardiac death or MI among the 941 patients without diabetes or CAD. Furthermore, TID was not predictive of coronary revascularization. ConclusionsThis study confirms a benign prognosis of TID with otherwise normal MPI in patients without diabetes or CAD, but cautions against extending this conclusion to high-risk individuals, particularly those with diabetes or CAD.

Detection of Obstructive Coronary Artery Disease Using Regadenoson Stress and 82Rb PET/CT Myocardial Perfusion Imaging

Our objective was to study the diagnostic performance of regadenoson (82)Rb myocardial perfusion PET imaging to detect obstructive coronary artery disease (CAD). We studied 134 patients (mean age, 63 ± 12 y; mean body mass index, 31 ± 9 kg/m(2)) without known CAD (96 with coronary angiography and 38 with low pretest likelihood of CAD). Stress left ventricular ejection fraction (LVEF) minus rest LVEF defined LVEF reserve. The Duke score was used to estimate the anatomic extent of jeopardized myocardium. Regadenoson PET had a high sensitivity, 92% (95% confidence interval [CI], 83%-97%), in detecting obstructive CAD, with a normalcy rate of 97% (95% CI, 86%-99%), specificity of 77% (54/70 patients; 95% CI, 66%-86%), and area under the receiver-operator-characteristic curve of 0.847 (95% CI, 0.774-0.903; P < 0.001). Regadenoson PET demonstrated high sensitivity to detect CAD in patients with single-vessel CAD (89%; 95% CI, 70%-98%). The mean LVEF reserve was significantly higher in patients with normal myocardial perfusion imaging results (6.5% ± 5.4%) than in those with mild (4.3 ± 5.1, P = 0.03) and moderate to severe reversible defects (-0.2% ± 8.4%, P = 0.001). Also, mean LVEF reserve was significantly higher in patients with a low likelihood of CAD (7.2% ± 4.5%, P < 0.0001) and mild or moderate jeopardized myocardium than in those with significant jeopardized myocardium (score ≥ 6), -2.8% ± 8.3%. Regadenoson (82)Rb myocardial perfusion imaging is accurate for the detection of obstructive CAD. LVEF reserve is high in patients without significant ischemia or significant angiographic jeopardized myocardium.

Improved accuracy of myocardial perfusion SPECT for detection of coronary artery disease by machine learning in a large population

ObjectiveWe aimed to improve the diagnostic accuracy of myocardial perfusion SPECT (MPS) by integrating clinical data and quantitative image features with machine learning (ML) algorithms. Methods1,181 rest 201Tl/stress 99mTc-sestamibi dual-isotope MPS studies [713 consecutive cases with correlating invasive coronary angiography (ICA) and suspected coronary artery disease (CAD) and 468 with low likelihood (LLk) of CAD <5%] were considered. Cases with stenosis <70% by ICA and LLk of CAD were considered normal. Total stress perfusion deficit (TPD) for supine/prone data, stress/rest perfusion change, and transient ischemic dilatation were derived by automated perfusion quantification software and were combined with age, sex, and post-electrocardiogram CAD probability by a boosted ensemble ML algorithm (LogitBoost). The diagnostic accuracy of the model for prediction of obstructive CAD ≥70% was compared to standard prone/supine quantification and to visual analysis by two experienced readers utilizing all imaging, quantitative, and clinical data. Tenfold stratified cross-validation was performed. ResultsThe diagnostic accuracy of ML (87.3% ± 2.1%) was similar to Expert 1 (86.0% ± 2.1%), but superior to combined supine/prone TPD (82.8% ± 2.2%) and Expert 2 (82.1% ± 2.2%) (P < .01). The receiver operator characteristic areas under curve for ML algorithm (0.94 ± 0.01) were higher than those for TPD and both visual readers (P < .001). The sensitivity of ML algorithm (78.9% ± 4.2%) was similar to TPD (75.6% ± 4.4%) and Expert 1 (76.3% ± 4.3%), but higher than that of Expert 2 (71.1% ± 4.6%), (P < .01). The specificity of ML algorithm (92.1% ± 2.2%) was similar to Expert 1 (91.4% ± 2.2%) and Expert 2 (88.3% ± 2.5%), but higher than TPD (86.8% ± 2.6%), (P < .01). ConclusionML significantly improves diagnostic performance of MPS by computational integration of quantitative perfusion and clinical data to the level rivaling expert analysis.

Improved Accuracy of Myocardial Perfusion SPECT for the Detection of Coronary Artery Disease Using a Support Vector Machine Algorithm

We aimed to improve the diagnostic accuracy of automatic myocardial perfusion SPECT (MPS) interpretation analysis for the prediction of coronary artery disease (CAD) by integrating several quantitative perfusion and functional variables for noncorrected (NC) data by Support Vector Machine (SVM) algorithm, a computer method for machine learning. Rest-stress gated (99m)Tc MPS NC studies (n = 957) from 623 consecutive patients with correlating invasive coronary angiography and 334 with a low likelihood of CAD (<5%) were assessed. Stenosis ≥50% in left main or ≥70% in all other vessels was considered abnormal. Total perfusion deficit (TPD) was computed automatically. In addition, ischemic changes (ISCHs) and ejection fraction changes (EFCs) between stress and rest were derived by quantitative software. The SVM was trained using a group of 125 patients (25 with low-likelihood, 25 with 0-vessel, 25 with 1-vessel, 25 with 2-vessel, and 25 with 3-vessel CAD) with the above quantitative variables and second-order polynomial fitting. The remaining patients (n = 832) were categorized using probability estimates, with CAD defined as a probability estimate ≥ 0.50. The diagnostic accuracy of SVM was also compared with visual segmental scoring by 2 experienced readers. The sensitivity of SVM (84%) was significantly better than ISCH (75%, P < 0.05) and EFC (31%, P < 0.05). The specificity of SVM (88%) was significantly better than TPD (78%, P < 0.05) and EFC (77%, P < 0.05). The diagnostic accuracy of SVM (86%) was significantly better than TPD (81%), ISCH (81%), or EFC (46%) (P < 0.05 for all). The receiver-operating-characteristic (ROC) area under the curve for SVM (0.92) was significantly better than TPD (0.90), ISCH (0.87), and EFC (0.64) (P < 0.001 for all). The diagnostic accuracy of SVM was comparable to the overall accuracy of both visual readers (86% vs. 84%, P = NS). The ROC area under the curve for SVM (0.92) was significantly better than that of both visual readers (0.87 and 0.88, P < 0.03). Computational integration of quantitative perfusion and functional variables using the SVM approach significantly improves the diagnostic accuracy of MPS and can significantly outperform visual assessment based on ROC analysis.

Phase II Safety and Clinical Comparison With Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging for Detection of Coronary Artery Disease

This was a phase II trial to assess flurpiridaz F 18 for safety and compare its diagnostic performance for positron emission tomography (PET) myocardial perfusion imaging (MPI) with Tc-99m single-photon emission computed tomography (SPECT) MPI with regard to image quality, interpretative certainty, defect magnitude, and detection of coronary artery disease (CAD) (≥50% stenosis) on invasive coronary angiography (ICA).In pre-clinical and phase I studies, flurpiridaz F 18 has shown characteristics of an essentially ideal MPI tracer.One hundred forty-three patients from 21 centers underwent rest-stress PET and Tc-99m SPECT MPI. Eighty-six patients underwent ICA, and 39 had low-likelihood of CAD. Images were scored by 3 independent, blinded readers.A higher percentage of images were rated as excellent/good on PET versus SPECT on stress (99.2% vs. 88.5%, p < 0.01) and rest (96.9% vs. 66.4, p < 0.01) images. Diagnostic certainty of interpretation (percentage of cases with definitely abnormal/normal interpretation) was higher for PET versus SPECT (90.8% vs. 70.9%, p < 0.01). In 86 patients who underwent ICA, sensitivity of PET was higher than SPECT (78.8% vs. 61.5%, respectively, p = 0.02). Specificity was not significantly different (PET: 76.5% vs. SPECT: 73.5%). Receiver-operating characteristic curve area was 0.82 ± 0.05 for PET and 0.70 ± 0.06 for SPECT (p = 0.04). Normalcy rate was 89.7% with PET and 97.4% with SPECT (p = NS). In patients with CAD on ICA, the magnitude of reversible defects was greater with PET than SPECT (p = 0.008). Extensive safety assessment revealed that flurpiridaz F 18 was safe in this cohort.In this phase 2 trial, PET MPI with flurpiridaz F 18 was safe and superior to SPECT MPI for image quality, interpretative certainty, and overall CAD diagnosis.

The NICE guidelines on the assessment of chest pain

The National Institute for Health and Clinical Excellence (NICE) published guidelines on the investigation of patients with chest pain of recent onset. The most prominent change to current protocols is that calcium scoring is proposed as the first-line investigation in patients with an estimated likelihood of coronary artery disease (CAD) of 10–29%, proceeding to multidetector computed tomography coronary angiography (CTCA) if the calcium score is above zero.1 For patients with 30–60% likelihood of CAD, functional testing is recommended with stress echocardiography, single photon emission computed tomography (SPECT) or cardiac magnetic resonance (CMR). For patients with 61–90% likelihood of CAD or calcium score greater than 400, X-ray invasive coronary angiography is recommended. The rationale underpinning these recommendations is that cardiac CT is considered an accurate ‘rule out’ test in patients with low likelihood of CAD given the extensive data confirming excellent prognosis of a zero calcium score in asymptomatic populations, and the excellent negative predictive value of CTCA.2 Functional tests on the other hand have better diagnostic performance in patients with higher pretest likelihood of CAD than in patients with low likelihood (Bayes theorem). It is hoped that the guidelines will reduce the high rate of normal coronary arteries at X-ray invasive coronary angiography, which was 39% in a recent ACC National Cardiovascular Data Registry, and is likely to be similar in most NHS Trusts.3 As exercise tolerance testing is no longer recommended; the guidelines will lead to an increase in referrals for imaging functional tests. The choice of imaging modality has been deliberately left open in the guidelines. Although this choice will often be driven by local availability, there are some differences in the evidence base and diagnostic yield and with the increasing awareness of the risks of ionizing radiation from medical exposure, the cumulative radiation burden of patients in their diagnostic journey, warrants particular consideration. Until recently, the median radiation dose for CTCA has been as high as 22 mSv, which can equate to an estimated risk of future cancer of 1 in every 270 in 40-year-old women undergoing the test.4 However, it is now possible to significantly reduce the radiation dose from CTCA by reducing the scan length and the scanning field of view to cover just the heart, electrocardiographically controlled tube current modulation during the cardiac cycle and reduction of the output of computed tomography X-ray tube from 120 kVp to 100 kVp for non-obese patients. The most effective way to lower the radiation dose, suitable in patients with regular heart rates below 60 bpm, is prospective electrocardiogram-triggering, which limits the acquisition to 10% of the cardiac cycle reducing the dose to 2–4 mSv.5 This is lower than conventional X-ray invasive coronary angiography, but not the new dual axis rotational coronary angiography which reduces radiation dose and contrast load. Such low radiation doses will however not be achievable in many UK centres without some investment.

Quantitative Upright–Supine High-Speed SPECT Myocardial Perfusion Imaging for Detection of Coronary Artery Disease: Correlation with Invasive Coronary Angiography

A recently developed camera system for high-speed SPECT (HS-SPECT) myocardial perfusion imaging shows excellent correlation with conventional SPECT. Our goal was to test the diagnostic accuracy of an automated quantification of combined upright and supine myocardial SPECT for detection of coronary artery disease (CAD) (≥ 70% luminal diameter stenosis or, in left main coronary artery, ≥ 50% luminal diameter stenosis) in comparison to invasive coronary angiography (ICA). We studied 142 patients undergoing upright and supine HS-SPECT, including 56 consecutive patients (63% men; mean age ± SD, 64 ± 13 y; 45% exercise stress) without known CAD who underwent diagnostic ICA within 6 mo of HS-SPECT and 86 consecutive patients with a low likelihood of CAD. Reference limits for upright and supine HS-SPECT were created from studies of patients with a low likelihood of CAD. Automated software adopted from supine-prone analysis was used to quantify the severity and extent of perfusion abnormality and was expressed as total perfusion deficit (TPD). TPD was obtained for upright (U-TPD), supine (S-TPD), and combined upright-supine acquisitions (C-TPD). Stress U-TPD ≥ 5%, S-TPD ≥ 5%, and C-TPD ≥ 3% myocardium were considered abnormal for per-patient analysis, and U-TPD, S-TPD, and C-TPD ≥ 2% in each coronary artery territory were considered abnormal for per-vessel analysis. On a per-patient basis, the sensitivity was 91%, 88%, and 94% for U-TPD, S-TPD, and C-TPD, respectively, and specificity was 59%, 73%, and 86% for U-TPD, S-TPD, and C-TPD, respectively. C-TPD had a larger area under the receiver-operating-characteristic curve than U-TPD or S-TPD for identification of stenosis ≥ 70% (0.94 vs. 0.88 and 0.89, P < 0.05 and not significant, respectively). On a per-vessel basis, the sensitivity was 67%, 66%, and 69% for U-TPD, S-TPD, and C-TPD, respectively, and specificity was 91%, 94%, and 97% for U-TPD, S-TPD, and C-TPD, respectively (P = 0.02 for specificity U-TPD vs. C-TPD). In this first comparison of HS-SPECT with ICA, new automated quantification of combined upright and supine HS-SPECT shows high diagnostic accuracy for detecting clinically significant CAD, with findings comparable to those reported using conventional SPECT.

Value of leads V4R and CM5 in the detection of coronary artery disease during exercise electrocardiographic test

The usefulness of the right precordial unipolar leads and the value of the bipolar lead CM5 in the detection of coronary artery disease (CAD) with exercise electrocardiographic (ECG) test are not well documented. The objective of this study was to evaluate the diagnostic performance of leads V4R and CM5. The study population comprised 579 patients referred for a bicycle exercise ECG test in the Finnish Cardiovascular Study. Patients were divided into three groups: angiographically proven CAD (CAD, n = 255), no CAD by angiography (NoCAD, n = 126), and low likelihood of CAD (LLC, n = 198). The maximum ST-segment depression at peak exercise was used as a parameter, and the diagnostic accuracy of different leads was assessed by receiver operating characteristic (ROC) analysis. Sensitivity and specificity values at a cut-off criterion of -0.10 mV ST-segment, 1-mm ST depression, were determined. According to the results, incorporating lead V4R with the standard leads decreased the ROC area from 0.71 to 0.69 (comparison CAD versus LLC) and from 0.55 to 0.53 (comparison CAD versus NoCAD) and had no effect on sensitivity or specificity. Adding lead CM5 to the standard leads did not affect the ROC area but increased the sensitivity and decreased the specificity. In conclusion, the use of right precordial lead V4R along with the standard 12-lead system does not improve the performance of the exercise ECG in diagnosing CAD. Adding lead CM5 to the standard leads increases the sensitivity but does not change the overall diagnostic performance.