Clinical significance of the hemodynamic gain index in patients undergoing exercise stress testing and coronary computed tomography angiography.

BACKGROUND: Many hemodynamic parameters provide limited information regarding obstructive coronary artery disease (CAD) during exercise stress testing particularly when exercise is suboptimal. Hemodynamic gain index (HGI) is a recent sensitive indicator of ischemia and has been associated with increased mortality. This study evaluated the clinical impact of HGI in patients who underwent concomitant exercise stress testing and coronary computed tomography angiography (CCTA). METHODS: A total of 284 consecutive patients from the executive health program between 2010 and 2018 were identified. Resting and peak heart rate (HR) as well as systolic blood pressure (SBP) measurements were recorded. Framingham risk score (FRS), Duke treadmill score (DTS) and HGI [Formula: see text] were calculated. The latter was divided into quartiles. CCTA was used as a reference test to detect any CAD. Multivariate analysis and artificial neural network were used to determine the independent predictors of obstructive CAD. RESULTS: Mean age was 53 ± 12 years with 83% male. Mean HGI was 1.74 ± 0.67, with cut-off value of severely blunted HGI ≤ 1.25 (Quartile 4). Patients with severely blunted HGI were older, had higher FRS, and worse DTS. Patients with obstructive CAD had lower HGI when compared to those with normal CCTA/non-obstructive CAD (1.36 ± 0.53 vs. 1.77 ± 0.67, P = 0.005), and showed a higher prevalence of severely blunted HGI (44% vs. 22%, P = 0.019). After adjusting for traditional risk factors, HGI remained an independent predictor of obstructive CAD while severely blunted HGI was associated with threefold increased odds of having obstructive CAD (P = 0.05). Using artificial intelligence analysis, severely blunted HGI independently predicted obstructive CAD with an area under the curve of 0.83 and 0.96, and normalized importance of HGI of 100% and 63%, respectively for different models. CONCLUSIONS: Among patients who underwent concomitant exercise stress testing and CCTA, severely blunted HGI independently predicted obstructive CAD after multivariate adjustment for traditional risk factors.

Association between left ventricular diastolic dysfunction and subclinical coronary artery calcification.

BACKGROUND: Assessment of diastolic dysfunction (DD) by echocardiography is an integral part of the evaluation of patients with normal ejection fraction and symptoms suggestive of heart failure. However, many patients with DD are asymptomatic. Computed tomography calcium scoring (CTCS) is often used to assess patients at low-intermediate risk for coronary artery disease (CAD). The purpose of this study was to evaluate the association of DD with subclinical coronary artery calcification. METHODS: Consecutive patients presenting for executive checkup who underwent resting transthoracic echocardiography followed by CTCS were retrospectively identified between January 2010 and December 2014. Two-dimensional and tissue Doppler imaging parameters were analyzed for assessing and grading of DD. Coronary artery calcium (CAC) score was quantified. RESULTS: A total of 191 patients (mean age 52 ± 12 years, 17% age ≥65, 20% with diabetes) were included. Of them, 69 (36%) patients had DD. Patients with higher CAC score were older, had more comorbidities, lower e', and were more likely to have DD. In the multivariate analysis, DD alone, age >65 years, or both were associated with almost threefold increase of subclinical atherosclerosis. After propensity analysis, DD was still associated with increased odds ratio (OR) for subclinical CAC (OR 3.66 [1.54-8.72], P-value .03) and similarly for e' < 10 cm/s. Compared to patients age <65 years and normal diastolic function, those age >65 years or DD had OR 3.49 (1.45-8.35) (P-value .005) for subclinical coronary atherosclerosis (CAC > 0), whereas those age >65 and DD had OR 9.30 (2.00-42) (P-value .004). CONCLUSIONS: Our analysis suggests that DD was strongly associated with CAC > 0, particularly among those age <65 years. Assessment of CAC as part of the routine clinical evaluation of patients with normal EF and atypical symptoms without a history of coronary atherosclerotic disease is warranted for further risk stratification.

Multimodality imaging for evaluation of chest pain using strain analysis at rest and peak exercise.

BACKGROUND: Exercise stress echocardiography (SE) is commonly used for diagnosing coronary artery disease (CAD). The use of quantitative echocardiographic measures such as strain imaging is expected to improve the sensitivity of conventional SE which relies on the visual diagnosis of wall-motion abnormalities (WMAs). This study is set to demonstrate the added value of resting and exercise strain analysis to detect underlying microangiopathy and inducible myocardial ischemia during a resting and SE in comparison with the results of coronary computed tomographic angiogram (CCTA). METHODS: A total of 103 consecutive outpatients from the executive screening program were identified and underwent resting and SE. Global longitudinal strain (GLS) and wall-motion changes at rest and peak exercise were analyzed and compared. Baseline demographics, heart rate, and blood pressure measurements were retrospectively extracted for analysis. CCTA was chosen as an alternative test to match with wall motion and strain imaging. RESULTS: Patients who had abnormal CCTA had lower resting GLS (14.85% ± 3.05 vs 17.99% ± 2.88, P-value = .001) when compared to patients with normal CCTA. All patients who had abnormal CCTA had higher wall-motion score index (1.35 ± 0.2 vs 1.00, P-value < .0001) and lower and abnormal peak stress GLS (pGLS) as compared to patients with normal CCTA (14.89% ± 3.35 vs 18.44% ± 4.27, P-value = .007). However, all patients with pGLS ≥ 20% had normal/nonobstructive CCTA. Patients with multiple comorbidities showed reduced and lower values of resting and pGLS (P-value < .0001), suggesting associated subclinical left ventricular dysfunction. CONCLUSIONS: Global longitudinal strain offers quantitative interpretation of the resting and SE study, detects underlying subclinical left ventricular dysfunction and a peak stress value more than 20% excludes obstructive CAD on CCTA.

Association of waterpipe smoking with myocardial infarction and determinants of metabolic syndrome among catheterized patients.

BACKGROUND: Waterpipe smoking is a rising global public health epidemic perceived by many users to be less harmful, though its toxicity overlaps or even exceeds that of cigarette smoking. Short-term cardiovascular changes due to waterpipe smoking are well established, but longer-term health impacts are still not fully elucidated. OBJECTIVE: We aim to investigate the association of waterpipe smoking with myocardial infarction among patients undergoing cardiac catheterization. METHODS: The study was performed on Lebanese patients referred for cardiac catheterization. Patient's blood was collected for metabolic measures and questionnaires were filled out to include socio-demographic, behavioral and pertinent medical characteristics of the study subjects. RESULTS: Myocardial infarction is significantly and independently associated with waterpipe smoking, with odds ratio (OR) of 1.329 (95% CI: [1.04-1.68]; p = .021), which is lower than that for cigarette smoking (OR = 1.87, 95% CI: [1.63-2.15]; p < .001). Only diabetes showed significant association with waterpipe smoking among MI enrollees (OR = 1.66, 95%CI: [1.04-2.63]; p = .032). CONCLUSION: The study provides yet another evidence for the adverse cardiovascular effects of waterpipe smoking on a clinical level. The harmful effects of waterpipe smoking should be underscored by health care professionals.

Unusual digoxin toxicity with myocardial injury.

A 38-year-old healthy male presented with vomiting and profuse diarrhea, associated with blurry and yellow coloration of the vision (xanthopsia). Laboratory workup was unremarkable, except for hyperkalemia (K 5.2 mEq/L) and mildly elevated troponin level 0.11 ng/mL (cut-off value 0.08). An electrocardiogram showed sinus bradycardia with deep scooping of the T waves. Although the patient denied intake of any drugs, herbs, consumption of plants, a digoxin level was drawn and was significantly elevated >5ng/mL (therapeutic range 0.8-2.0). Further questioning revealed that the patient was a pharmacist mixing raw material to fabricate medication, and that he could have incidentally ingested contaminated water. His symptoms improved with parallel improvement in the electrocardiogram T wave abnormalities. An echocardiogram was normal. The positive troponin was felt to be secondary to severe digoxin toxicity. Review of the literature however showed no report of elevated troponin in the setting of digoxin toxicity.

Impact of inflammation, gene variants, and cigarette smoking on coronary artery disease risk.

BACKGROUND: The role of inflammation in coronary artery disease (CAD) pathogenesis is well recognized. Moreover, smoking inhalation increases the activity of inflammatory mediators through an increase in leukotriene synthesis essential in atherosclerosis pathogenesis. AIM: The aim of this study is to investigate the effect of "selected" genetic variants within the leukotriene (LT) pathway and other variants on the development of CAD. METHODS: CAD was detected by cardiac catheterization. Logistic regression was performed to investigate the association of smoking and selected susceptibility variants in the LT pathway including ALOX5AP, LTA4H, LTC4S, PON1, and LTA as well as CYP1A1 on CAD risk while controlling for age, gender, BMI, family history, diabetes, hyperlipidemia, and hypertension. RESULTS: rs4769874 (ALOX5AP), rs854560 (PON1), and rs4646903 (CYP1A1 MspI polymorphism) are significantly associated with an increased risk of CAD with respective odds ratios of 1.53703, 1.67710, and 1.35520; the genetic variant rs9579646 (ALOX5AP) is significantly associated with a decreased risk of CAD (OR 0.76163). Moreover, a significant smoking-gene interaction is determined with CYP1A1 MspI polymorphism rs4646903 and is associated with a decreased risk of CAD in current smokers (OR 0.52137). CONCLUSION: This study provides further evidence that genetic variation of the LT pathway, PON1, and CYP1A1 can modulate the atherogenic processes and eventually increase the risk of CAD in our study population. Moreover, it also shows the effect of smoking-gene interaction on CAD risk, where the CYP1A1 MspI polymorphism revealed a decreased risk in current smokers.

Circulating lipid levels and risk of coronary artery disease in a large group of patients undergoing coronary angiography.

A main underlying pathology of coronary artery disease is the deposition of cholesterol in the arteries supplying blood to the heart that leads to stenosis and myocardial infarction. We tested if dyslipidemia is a risk factor for coronary artery disease in the Lebanese population, and studied the role of the total cholesterol/HDL cholesterol (TC/HDL-C) ratio as a biological marker of coronary artery disease. We recruited 6,180 Lebanese patients undergoing cardiac catheterization. We conducted a cross-sectional association study between TC/HDL-C ratio and the number and type of vessels occluded in catheterized patients by controlling for confounding effects. The TC/HDL-C ratio ≥4 significantly predicts ≥50 % stenosis in all vessels individually with the odds ratio (OR) ranging from 1.22 to 1.92. The OR increased with increasing number of ≥50 % stenotic vessels (1.39 for 2 vessels and 1.64 for 3-4 vessels), as did risk due to diabetes, CAD family history, gender, and age. The younger than average age of onset subgroup shows a pronounced increase in risk for occlusion of the left main coronary artery due to TC/HDL-C ≥4 (OR 3.26). In conclusion, low levels of HDL-cholesterol and high levels TC/HDL-C ratio are strong biological markers of disease occurrence and severity in the Lebanese population.

Extraction of a tunneled jugular defibrillator lead via a superior approach.

Extraction of cardiac implantable electrical devices (CIED) is becoming an increasing necessity. Infection is among the most frequent and serious complications associated with the surge of CIED implants. We describe the extraction of an infected cardiac resynchronization therapy-defibrillator (CRT-D) in a patient with a tunneled implantable cardioverter defibrillator (ICD) lead implanted from the right jugular vein.

Echocardiogram-Guided Diagnosis of Anomalous Coronary Arteries: A Rare Presentation.

Incidentaloma, a term that embodies the detection of certain problems during the performance of unreasonable investigations, resonates in the medical field. Retroaortic coronary sign is a recently recognized echocardiographic feature of the anomalous coronary artery. It is typically associated with anomalies of the left coronary artery, especially the left circumflex artery. As far as has been monitored, few echocardiographic signs that correlate with this feature have been identified. This feature often remains underdiagnosed on transthoracic echocardiograms due to confusion with artifacts, calcifications, and other cardiac structures. A 45-year-old male patient underwent regular cardiac routine assessment. Retroaortic anomalous coronary (RAC) sign was incidentally detected by transthoracic thoracic echocardiogram; consequently, the retroaortic route of the coronary artery was suspected. Coronary computed tomography angiography was requested to confirm the seen echocardiographic signs. After a 3D reconstruction imaging, the left circumflex retroaortic course was identified with right coronary sinus origin. This case ensures the importance of transthoracic echocardiography as a noninvasive tool in diagnosing anomalous coronary arteries. These anomalies are usually diagnosed by coronary computed tomography angiography and coronary angiography, mainly in the presence of retroaortic coronary sign or "crossed aorta sign."

Coronary Artery Aneurysm: Its Evaluation in a 27-Year-Old Female Patient, Prognosis, and Suggested Treatment Strategies.

Coronary artery aneurysm (CAA) is characterized by a localized dilation of one or more of the coronary arteries with multiple etiologies, including congenital, acquired, or connected to auto-inflammatory diseases with multiple shapes and classifications. It is usually diagnosed incidentally during coronary imaging and can have variable clinical outcomes, ranging from asymptomatic to sudden cardiac death with a generally poor prognosis. Management of this condition faces a clinical dilemma due to the lack of clear guidelines or randomized trials. Treatment should be individualized based on symptoms, shape, and comorbidities. Herein, we present the case report of a 27-year-old female patient with no prior medical conditions. However, she presented with palpitations, and a compressive mass located over the right atrium was identified in the patient. After undergoing cardiac catheterization and coronary scanning, a giant aneurysm of the sinoatrial branch was detected with an aneurysmal left main that was retrieved surgically with good recovery and postoperative course.

Genetic Variants in PHACTR1 & LPL Mediate Restenosis Risk in Coronary Artery Patients.

Background and Objective: Coronary artery disease (CAD) is a major cause of death worldwide. Revascularization via stent placement or coronary artery bypass grafting (CABG) are standard treatments for CAD. Despite a high success rate, these approaches are associated with long-term failure due to restenosis. Risk factors associated with restenosis were investigated using a case-control association study design. Methods: Five thousand two hundred and forty-two patients were enrolled in this study and were assigned as follows: Stenosis Group: 3570 patients with CAD >50% without a prior stent or CABG (1394 genotyped), and Restenosis Group: 1672 patients with CAD >50% and prior stent deployment or CABG (705 genotyped). Binomial regression models were applied to investigate the association of restenosis with diabetes, hypertension, and dyslipidemia. The genetic association with restenosis was conducted using PLINK 1.9. Results: Dyslipidemia is a major risk factor (Odds Ratio (OR) = 2.14, P-value <0.0001) for restenosis particularly among men (OR = 2.32, P < 0.0001), while type 2 diabetes (T2D) was associated with an increased risk of restenosis in women (OR = 1.36, P = 0.01). The rs9349379 (PHACTR1) and rs264 (LPL) were associated with an increased risk of restenosis in our patients. PHACTR1 variant was associated with increased risk of restenosis mainly in women and in diabetic patients, while the LPL variant was associated with increased risk of restenosis in men. Conclusion: The rs9349379 in PHACTR1 gene is significantly associated with restenosis, this association is more pronounced in women and in diabetic patients. The rs264 in LPL gene was associated with increased risk of restenosis in male patients.

Homocysteine levels, H-Hypertension, and the MTHFR C677T genotypes: A complex interaction.

Background and objectives: High homocysteine levels are associated with increased risk of hypertension and stroke. Homocysteine is metabolized by the methylenetetrahydrofolate reductase (MTHFR). We aimed to investigate the levels of homocysteine and their association with hypertension, stroke, and antihypertensive medication usage in patients with different MTHFR C677T genotypes. Methods and results: Genotype frequency of MTHFR polymorphism was performed, and plasma homocysteine levels were measured in 2,640 adult Lebanese patients. Hypertension, history of stroke, and list of medications were documented, among other clinical and demographic parameters. The TT mutant genotype and the T mutant allele of MTHFR were more prevalent in hyperhomocysteinemia (HHcy) and H-hypertensive (H-HTN, defined as hypertension with hyperhomocysteinemia) patients when compared to non-HHcy subjects and non H-HTN patients respectively. Homocysteine levels were significantly higher in hypertensive patients specifically among those on diuretics. A higher level of homocysteine was found in hypertensive patients with the MTHFR T allele compared to patients carrying the C allele. Among the T allele carriers, the average plasma homocysteine level was 13.3 ± 0.193 µmol/L for hypertensive subjects compared to 11.9 ± 0.173 µmol/L (non-hypertensives). Furthermore, homocysteine levels significantly correlated with stroke risk in patients with the T alleles. Conclusions: We found an association of homocysteine with hypertension, hypertensive medication, and stroke risk among patients with the MTHFR T allele and the TT genotype. The association of diuretics therapy with higher homocysteine levels calls for routine measurements and therapeutic control of homocysteine in patients on diuretic, to improve health-related outcomes.

Elevated Lp(a) Levels Correlate with Severe and Multiple Coronary Artery Stenotic Lesions.

Backgrounds and Aims: The role of Lipoprotein(a) (Lp(a)) in increasing the risk of cardiovascular diseases is reported in several populations. The aim of this study is to investigate the correlation of high Lp(a) levels with the degree of coronary artery stenosis. Methods: Two hundred and sixty-eight patients were enrolled for this study. Patients who underwent coronary artery angiography and who had Lp(a) measurements available were included in this study. Binomial logistic regressions were applied to investigate the association between Lp(a) and stenosis in the four major coronary arteries. The effect of LDL and HDL Cholesterol on modulating the association of Lp(a) with coronary artery disease (CAD) was also evaluated. Multinomial regression analysis was applied to assess the association of Lp(a) with the different degrees of stenosis in the four major coronary arteries. Results: Our analyses showed that Lp(a) is a risk factor for CAD and this risk is significantly apparent in patients with HDL-cholesterol ≥35 mg/dL and in non-obese patients. A large proportion of the study patients with elevated Lp(a) levels had CAD even when exhibiting high HDL serum levels. Increased HDL with low Lp(a) serum levels were the least correlated with stenosis. A significantly higher levels of Lp(a) were found in patients with >50% stenosis in at least two major coronary vessels arguing for pronounced and multiple stenotic lesions. Finally, the derived variant (rs1084651) of the LPA gene was significantly associated with CAD. Conclusion: Our study highlights the importance of Lp(a) levels as an independent biological marker of severe and multiple coronary artery stenosis.

Epicardial Fat Necrosis After COVID-19 Infection: A Case Report.

Epipericardial or epicardial fat necrosis (EFN) is a self-limited inflammatory process occurring in the mediastinal fat surrounding the heart. It is an uncommon cause of acute chest pain and mimics more critical clinical disorders such as acute coronary syndrome, aortic dissection, and pulmonary embolism. However, EFN is frequently overlooked and under-recognized in emergency departments (EDs) owing to the unfamiliarity of this condition among physicians and radiologists. Herein, we present the case of a previously healthy young male patient, with a recent history of mild COVID-19 infection (two weeks before presentation), who presented to the ED for acute chest pain. Paraclinical evaluation including computed tomography (CT) of the chest revealed fat stranding along with the left epicardial fat pad in favor of EFN.

Focal Myocarditis As the First Sign in the Presentation of a COVID-19 Infection: A Case Report.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Patients with COVID-19 typically present with symptoms and signs related to respiratory tract infection. However, a broad spectrum of cardiac manifestations including myocarditis has been reported as complications of this virus. Nevertheless, focal myocarditis as the first clinical manifestation of COVID-19 infection has not been reported before. Thus, we herein present the case of a 56-year-old male patient previously healthy and presented to the emergency department with chest pain. The clinical picture was compatible with inferior ST-elevation myocardial infarction (STEMI). Initial COVID-19 polymerase chain reaction (PCR) was negative, as well for its classic symptoms. Thereafter, further investigations suggested the diagnosis of focal myocarditis. Later on, the patient started to have a fever and repeated COVID-19 PCR that returned positive.

Value of myocardial work for assessment of myocardial adaptation to increased afterload in patients with high blood pressure at peak exercise.

Non-invasive myocardial work (MW) indices are superior to global longitudinal strain (GLS) to assess left ventricular (LV) mechanics in situations where afterload is abnormally high. The rotational motion of the apex provides an accurate index of LV contractility. To date, there are no data about MW values during stress echocardiography (SE), particularly for the apex. Our study aims at assessing MW indices at peak exercise to better understand LV mechanics in patients with high peak systolic blood pressure (SBP). A total of 81 patients without structural or ischemic heart disease referred for SE between January and June 2019 were included. BP measurements, GLS and MW indices were performed at rest and peak exercise. In order to quantify the role of the apex, apical work fraction (AWF) was also calculated and further stratified by peak SBP. A peak SBP > 180 mmHg was considered abnormally high. There were 36 (44%) patients who had peak SBP > 180 mmHg. They showed similar resting GLS and MW values when compared to control. However, peak stress global work index, constructive work and wasted work (GWW) increased significantly (P-value < 0.05), with a relatively constant global work efficiency. In the multivariate analysis, peak SBP > 180 mmHg was associated with threefold increased odds of abnormal peak GWW > 96.5 mmHg% (median value) (odds ratio 3.0, P-value 0.003). Apical work increased significantly when stratified by peak SBP (P-value 0.003) and AWF increased from 33 ± 3% to 37 ± 3% (rest-stress), P-value < 0.0001, but remained constant when stratified by peak SBP. Our analysis provides new data on MW indices at peak stress, particularly for patients with abnormal peak SBP response, and supports the role and the contribution of the apex to MW.

Diabetes without Manifest Cardiovascular Disease: A Novel Approach in Risk Stratification and Treatment Selection.

BACKGROUND: Cardiovascular disease (CVD), the main macro vascular complication of type 2 diabetes (T2D), increases the risk of death significantly in patients with T2D. INTRODUCTION: Most of the patients with T2D do not have obvious CVD symptoms. Due to the paucity of data, CVD screening in asymptomatic patients with T2D remains highly controversial. METHODS: This has driven a panel of experts to establish a novel consensus on how to approach patients with T2D at high CVD risk. The panel formulated a stepwise algorithm by which patients with T2D undergo initial risk stratification into low, intermediate and high risk using the ASCVD calculator. In patients with intermediate risk, coronary artery calcium measurement is used to further stratify those patients into new low and high-risk categories. RESULTS AND CONCLUSION: The panel recommends using standard diabetes care in low risk patients and using SGLT2 inhibitors and GLP1 agonists with cardio protective effect, on top of standard care, in high risk individuals.

Value of aortic arch analysis during routine transthoracic echocardiography in adults.

AIMS: Despite the recommendations of the American Society of Echocardiography, the majority of clinicians and sonographers do not perform aortic arch analysis routinely during transthoracic echocardiography (TTE). The European guidelines remain unclear. The aim of our study is to evaluate the usefulness of aortic arch analysis during routine TTE in adults. METHODS AND RESULTS: We performed aortic arch analysis on all 2000 adult patients (mean age 52, range 18-89) referred to our echocardiography lab for transthoracic echocardiograms between January and December 2007. Adequate study was obtained in 1826 patients (91% of cases). Suprasternal notch views and aortic arch analysis were normal in 1787 patients (98%) and abnormal in 39 patients (2%). Among patients with abnormal findings, 32 patients (82%) had aortic arch plaques, 24 of them (75%) had plaques <4 mm, and 8 patients (25%) had plaques > or =4 mm. Four patients (10%) had aortic arch aneurysms (diameter > or =4.5 cm). Other abnormal findings included one case of coarctation of the aorta, one case of a floating thrombus in a right pulmonary artery branch, one case of severe stenosis of the inominate artery, and one case of type A aortic dissection. Subsequently, 7 patients (18%) underwent surgery, 4 patients (10%) were started on oral anticoagulation therapy, and 28 patients (72%) treated with an antiplatelet and risk factors modification. CONCLUSION: Aortic arch analysis showed significant pathology in 2% of the adult population undergoing routine TTE. This led to therapeutic interventions in all patients with abnormal findings, and to curative therapy in more than quarter of them. Aortic arch analysis should be mandatory during a routine exam and part of any standard digital acquisition protocol for TTE in adults.

Incremental value of stress echocardiography and computed tomography coronary calcium scoring for the diagnosis of coronary artery disease.

Computed tomography coronary angiography (CTCA) has a higher negative predictive value (NPV) for coronary artery disease (CAD) than stress echocardiography (SE). CT calcium scoring (CTCS) allows detection and quantification of coronary artery calcification (CAC). The NPV of combined SE and CTCS for CAD is not well defined. Consecutive patients from the executive screening program who underwent exercise SE and concomitant CTCA were retrospectively identified between January 2010 and December 2014. Patients with normal SE and CAC score of zero were determined, and the presence or absence of any CAD (obstructive or non-obstructive plaques) on CTCA was confirmed. The NPV of combined SE and CTCS was then re-tested using a validation cohort of subsequent consecutive patients enrolled between January 2015 and July 2018. The initial cohort consisted of 173 patients (19% age > 65 years, 19% diabetic); 40% had normal CTCA, 48% with non-obstructive CTCA (77 with CAC score > 0), and 12% with obstructive CTCA (all with CAC score > 0). There were 16 (9.2%) patients with inducible ischemia on SE. A normal SE had a 93% NPV to exclude obstructive CAD but only 42% NPV to exclude any CAD. A combined normal SE and CTCS had a 100% NPV for obstructive CAD, and 92% for any CAD. In a validation cohort of 111 patients, a normal SE and CAC score of zero had NPV of 100% for obstructive CAD and 92% for any CAD. The combined cohort consisted of predominately low Framingham risk patients; more than 40% (70/181) had CAC score > 0 and 5/70 had obstructive CAD, with the remaining non-obstructive. A concomitant normal SE and CAC score of zero excluded obstructive CAD (NPV 100%) and any CAD in 92% of the testing and validation cohorts. CTCS seems to add incremental risk stratification, particularly for patients with low Framingham score.