Browsing by Author "Tamarappoo, Balaji K."
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Item Clinical Deployment of Explainable Artificial Intelligence of SPECT for Diagnosis of Coronary Artery Disease(Elsevier, 2022) Otaki, Yuka; Singh, Ananya; Kavanagh, Paul; Miller, Robert J. H.; Parekh, Tejas; Tamarappoo, Balaji K.; Sharir, Tali; Einstein, Andrew J.; Fish, Mathews B.; Ruddy, Terrence D.; Kaufmann, Philipp A.; Sinusas, Albert J.; Miller, Edward J.; Bateman, Timothy M.; Dorbala, Sharmila; Di Carli, Marcelo; Cadet, Sebastien; Liang, Joanna X.; Dey, Damini; Berman, Daniel S.; Slomka, Piotr J.; Medicine, School of MedicineBackground: Explainable artificial intelligence (AI) can be integrated within standard clinical software to facilitate the acceptance of the diagnostic findings during clinical interpretation. Objectives: This study sought to develop and evaluate a novel, general purpose, explainable deep learning model (coronary artery disease-deep learning [CAD-DL]) for the detection of obstructive CAD following single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Methods: A total of 3,578 patients with suspected CAD undergoing SPECT MPI and invasive coronary angiography within a 6-month interval from 9 centers were studied. CAD-DL computes the probability of obstructive CAD from stress myocardial perfusion, wall motion, and wall thickening maps, as well as left ventricular volumes, age, and sex. Myocardial regions contributing to the CAD-DL prediction are highlighted to explain the findings to the physician. A clinical prototype was integrated using a standard clinical workstation. Diagnostic performance by CAD-DL was compared to automated quantitative total perfusion deficit (TPD) and reader diagnosis. Results: In total, 2,247 patients (63%) had obstructive CAD. In 10-fold repeated testing, the area under the receiver-operating characteristic curve (AUC) (95% CI) was higher according to CAD-DL (AUC: 0.83 [95% CI: 0.82-0.85]) than stress TPD (AUC: 0.78 [95% CI: 0.77-0.80]) or reader diagnosis (AUC: 0.71 [95% CI: 0.69-0.72]; P < 0.0001 for both). In external testing, the AUC in 555 patients was higher according to CAD-DL (AUC: 0.80 [95% CI: 0.76-0.84]) than stress TPD (AUC: 0.73 [95% CI: 0.69-0.77]) or reader diagnosis (AUC: 0.65 [95% CI: 0.61-0.69]; P < 0.001 for all). The present model can be integrated within standard clinical software and generates results rapidly (<12 seconds on a standard clinical workstation) and therefore could readily be incorporated into a typical clinical workflow. Conclusions: The deep-learning model significantly surpasses the diagnostic accuracy of standard quantitative analysis and clinical visual reading for MPI. Explainable artificial intelligence can be integrated within standard clinical software to facilitate acceptance of artificial intelligence diagnosis of CAD following MPI.Item Diastolic dysfunction in women with ischemia and no obstructive coronary artery disease: Mechanistic insight from magnetic resonance imaging(Elsevier, 2021) Samuel, T. Jake; Wei, Janet; Sharif, Behzad; Tamarappoo, Balaji K.; Pattisapu, Varun; Maughan, Jenna; Cipher, Daisha J.; Suppogu, Nissi; Aldiwani, Haider; Thomson, Louise E. J.; Shufelt, Chrisandra; Berman, Daniel S.; Li, Debiao; Bairey Merz, C. Noel; Nelson, Michael D.; Medicine, School of MedicineBackground: Ischemia with no obstructive coronary artery disease (INOCA) is prevalent in women and is associated with increased risk of developing heart failure with preserved ejection fraction (HFpEF); however, the mechanism(s) contributing to this progression remains unclear. Given that diastolic dysfunction is common in women with INOCA, defining mechanisms related to diastolic dysfunction in INOCA could identify therapeutic targets to prevent HFpEF. Methods: Cardiac MRI was performed in 65 women with INOCA and 12 reference controls. Diastolic function was defined by left ventricular early diastolic circumferential strain rate (eCSRd). Contributors to diastolic dysfunction were chosen a priori as coronary vascular dysfunction (myocardial perfusion reserve index [MPRI]), diffuse myocardial fibrosis (extracellular volume [ECV]), and aortic stiffness (aortic pulse wave velocity [aPWV]). Results: Compared to controls, eCSRd was lower in INOCA (1.61 ± 0.33/s vs. 1.36 ± 0.31/s, P = 0.016); however, this difference was not exaggerated when the INOCA group was sub-divided by low and high MPRI (P > 0.05) nor was ECV elevated in INOCA (29.0 ± 1.9% vs. 28.0 ± 3.2%, control vs. INOCA; P = 0.38). However, aPWV was higher in INOCA vs. controls (8.1 ± 3.2 m/s vs. 6.1 ± 1.5 m/s; P = 0.045), and was associated with eCSRd (r = -0.50, P < 0.001). By multivariable linear regression analysis, aPWV was an independent predictor of decreased eCSRd (standardized β = -0.39, P = 0.003), as was having an elevated left ventricular mass index (standardized β = -0.25, P = 0.024) and lower ECV (standardized β = 0.30, P = 0.003). Conclusions: These data provide mechanistic insight into diastolic dysfunction in women with INOCA, identifying aortic stiffness and ventricular remodeling as putative therapeutic targets.Item Differences in Prognostic Value of Myocardial Perfusion SPECT using High-Efficiency Solid-State Detector Between Men and Women in a Large International Multi-Center Study(American Heart Association, 2022) Tamarappoo, Balaji K.; Otaki, Yuka; Sharir, Tali; Hu, Lien-Hsin; Gransar, Heidi; Einstein, Andrew J.; Fish, Mathews B.; Ruddy, Terrence D.; Kaufmann, Philipp; Sinusas, Albert J.; Miller, Edward J.; Bateman, Timothy M.; Dorbala, Sharmila; Di Carli, Marcelo; Eisenberg, Evann; Liang, Joanna X.; Dey, Damini; Berman, Daniel S.; Slomka, Piotr J.; Medicine, School of MedicineBackground: Semiquantitative assessment of stress myocardial perfusion defect has been shown to have greater prognostic value for prediction of major adverse cardiac events (MACE) in women compared with men in single-center studies with conventional single-photon emission computed tomography (SPECT) cameras. We evaluated sex-specific difference in the prognostic value of automated quantification of ischemic total perfusion defect (ITPD) and the interaction between sex and ITPD using high-efficiency SPECT cameras with solid-state detectors in an international multicenter imaging registry (REFINE SPECT [Registry of Fast Myocardial Perfusion Imaging With Next-Generation SPECT]). Methods: Rest and exercise or pharmacological stress SPECT myocardial perfusion imaging were performed in 17 833 patients from 5 centers. MACE was defined as the first occurrence of death or myocardial infarction. Total perfusion defect (TPD) at rest, stress, and ejection fraction were quantified automatically by software. ITPD was given by stressTPD-restTPD. Cox proportional hazards model was used to evaluate the association between ITPD versus MACE-free survival and expressed as a hazard ratio. Results: In 10614 men and 7219 women, with a median follow-up of 4.75 years (interquartile range, 3.7-6.1), there were 1709 MACE. In a multivariable Cox model, after adjusting for revascularization and other confounding variables, ITPD was associated with MACE (hazard ratio, 1.08 [95% CI, 1.05-1.1]; P<0.001). There was an interaction between ITPD and sex (P<0.001); predicted survival for ITPD<5% was worse among men compared to women, whereas survival among women was worse than men for ITPD≥5%, P<0.001. Conclusions: In the international, multicenter REFINE SPECT registry, moderate and severe ischemia as quantified by ITPD from high-efficiency SPECT is associated with a worse prognosis in women compared with men.Item Impact of Early Revascularization on Major Adverse Cardiovascular Events in Relation to Automatically Quantified Ischemia(Elsevier, 2021) Azadani, Peyman N.; Miller, Robert J. H.; Sharir, Tali; Diniz, Marcio A.; Hu, Lien-Hsin; Otaki, Yuka; Gransar, Heidi; Liang, Joanna X.; Eisenberg, Evann; Einstein, Andrew J.; Fish, Mathews B.; Ruddy, Terrence D.; Kaufmann, Philipp A.; Sinusas, Albert J.; Miller, Edward J.; Bateman, Timothy M.; Dorbala, Sharmila; Di Carli, Marcelo; Tamarappoo, Balaji K.; Dey, Damini; Berman, Daniel S.; Slomka, Piotr J.; Medicine, School of MedicineObjectives: Using a contemporary, multicenter international single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) registry, this study characterized the potential major adverse cardiovascular event(s) (MACE) benefit of early revascularization based on automatic quantification of ischemia. Background: Prior single-center data reported an association between moderate to severe ischemia SPECT-MPI and reduced cardiac death with early revascularization. Methods: Consecutive patients from a multicenter, international registry who underwent 99mTc SPECT-MPI between 2009 and 2014 with solid-state scanners were included. Ischemia was quantified automatically as ischemic total perfusion deficit (TPD). Early revascularization was defined as within 90 days. The primary outcome was MACE (death, myocardial infarction, and unstable angina). A propensity score was developed to adjust for nonrandomization of revascularization; then, multivariable Cox modeling adjusted for propensity score and demographics was used to predict MACE. Results: In total, 19,088 patients were included, with a mean follow-up of 4.7 ± 1.6 years, during which MACE occurred in 1,836 (9.6%) patients. There was a significant interaction between ischemic TPD modeled as a continuous variable and early revascularization (interaction p value: 0.012). In this model, there was a trend toward reduced MACE in patients with >5.4% ischemic TPD and a significant association with reduced MACE in patients with >10.2% ischemic TPD. Conclusions: In this large, international, multicenter study reflecting contemporary cardiology practice, early revascularization of patients with >10.2% ischemia on SPECT-MPI, quantified automatically, was associated with reduced MACE.Item Mean Heart Dose Is an Inadequate Surrogate for Left Anterior Descending Coronary Artery Dose and the Risk of Major Adverse Cardiac Events in Lung Cancer Radiation Therapy(Elsevier, 2021) Atkins, Katelyn M.; Bitterman, Danielle S.; Chaunzwa, Tafadzwa L.; Kozono, David E.; Baldini, Elizabeth H.; Aerts, Hugo J. W. L.; Tamarappoo, Balaji K.; Hoffmann, Udo; Nohria, Anju; Mak, Raymond H.; Radiation Oncology, School of MedicinePurpose: Mean heart dose (MHD) over 10 Gy and left anterior descending (LAD) coronary artery volume (V) receiving 15 Gy (V15Gy) greater than 10% can significantly increase the risk of major adverse cardiac events (MACE) in patients with non-small cell lung cancer (NSCLC). We sought to characterize the discordance between MHD and LAD dose and the association of this classification on the risk of MACE after radiation therapy. Methods and materials: The coefficient of determination for MHD and LAD V15Gy was calculated in this retrospective analysis of 701 patients with locally advanced NSCLC treated with radiation therapy. Four groups were defined on the basis of high or low MHD (≥10 Gy vs <10 Gy) and LAD V15Gy (≥10% vs <10%). MACE (unstable angina, heart failure, myocardial infarction, coronary revascularization, and cardiac death) cumulative incidence was estimated, and Fine and Gray regressions were performed. Results: The proportion of variance in LAD V15Gy predictable from MHD was only 54.5% (R2 = 0.545). There was discordance (where MHD was high [≥10 Gy] and LAD low [V15Gy < 10%], or vice versa) in 23.1% of patients (n = 162). Two-year MACE estimates were 4.2% (MHDhigh/LADlow), 7.6% (MHDhigh/LADhigh), 1.8% (MHDlow/LADlow), and 13.0% (MHDlow/LADhigh). Adjusting for pre-existing coronary heart disease and other prognostic factors, MHDhigh/LADlow (subdistribution hazard ratio [SHR], 0.34; 95% CI, 0.13-0.93; P = .036) and MHDlow/LADlow (SHR, 0.24; 95% CI, 0.10-0.53; P < .001) were associated with a significantly reduced risk of MACE. Conclusions: MHD is insufficient to predict LAD V15Gy with confidence. When MHD and LAD V15Gy dose exposure is discordant, isolated low LAD V15Gy significantly reduces the risk of MACE in patients with locally advanced NSCLC after radiation therapy, suggesting that the validity of whole heart metrics for optimally predicting cardiac events should be reassessed.Item Metabolic syndrome, fatty liver, and artificial intelligence-based epicardial adipose tissue measures predict long-term risk of cardiac events: a prospective study(Springer Nature, 2021-01-29) Lin, Andrew; Wong, Nathan D.; Razipour, Aryabod; McElhinney, Priscilla A.; Commandeur, Frederic; Cadet, Sebastien J.; Gransar, Heidi; Chen, Xi; Cantu, Stephanie; Miller, Robert J. H.; Nerlekar, Nitesh; Wong, Dennis T. L.; Slomka, Piotr J.; Rozanski, Alan; Tamarappoo, Balaji K.; Berman, Daniel S.; Dey, Damini; Medicine, School of MedicineBackground: We sought to evaluate the association of metabolic syndrome (MetS) and computed tomography (CT)-derived cardiometabolic biomarkers (non-alcoholic fatty liver disease [NAFLD] and epicardial adipose tissue [EAT] measures) with long-term risk of major adverse cardiovascular events (MACE) in asymptomatic individuals. Methods: This was a post-hoc analysis of the prospective EISNER (Early-Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) study of participants who underwent baseline coronary artery calcium (CAC) scoring CT and 14-year follow-up for MACE (myocardial infarction, late revascularization, or cardiac death). EAT volume (cm3) and attenuation (Hounsfield units [HU]) were quantified from CT using fully automated deep learning software (< 30 s per case). NAFLD was defined as liver-to-spleen attenuation ratio < 1.0 and/or average liver attenuation < 40 HU. Results: In the final population of 2068 participants (59% males, 56 ± 9 years), those with MetS (n = 280;13.5%) had a greater prevalence of NAFLD (26.0% vs. 9.9%), higher EAT volume (114.1 cm3 vs. 73.7 cm3), and lower EAT attenuation (-76.9 HU vs. -73.4 HU; all p < 0.001) compared to those without MetS. At 14 ± 3 years, MACE occurred in 223 (10.8%) participants. In multivariable Cox regression, MetS was associated with increased risk of MACE (HR 1.58 [95% CI 1.10-2.27], p = 0.01) independently of CAC score; however, not after adjustment for EAT measures (p = 0.27). In a separate Cox analysis, NAFLD predicted MACE (HR 1.78 [95% CI 1.21-2.61], p = 0.003) independently of MetS, CAC score, and EAT measures. Addition of EAT volume to current risk assessment tools resulted in significant net reclassification improvement for MACE (22% over ASCVD risk score; 17% over ASCVD risk score plus CAC score). Conclusions: MetS, NAFLD, and artificial intelligence-based EAT measures predict long-term MACE risk in asymptomatic individuals. Imaging biomarkers of cardiometabolic disease have the potential for integration into routine reporting of CAC scoring CT to enhance cardiovascular risk stratification.Item Myocardial extracellular volume measurement using cardiac computed tomography(Springer, 2024) Muthalaly, Rahul G.; Abrahams, Timothy; Lin, Andrew; Patel, Kush; Tan, Sean; Dey, Damini; Han, Donghee; Tamarappoo, Balaji K.; Nicholls, Stephen J; Nerlekar, Nitesh; Medicine, School of MedicineMyocardial fibrosis is a common endpoint of many cardiac diseases and increasingly recognized as a predictor of heart failure, arrhythmia, and death. Recent studies have utilised cardiac computed tomography (CT) scans with delayed phase imaging to quantify diffuse fibrosis of the myocardium. CT extracellular volume (CT-ECV) measurement correlates well with CMR and histological myocardial fibrosis. Furthermore, CT-ECV predicts outcomes such as death, heart failure and arrhythmia in various disease states. This review summarizes the rationale and methodology behind CT-ECV measurement and provides a detailed summary of the current clinical evidence for the use of CT-ECV.Item Prediction of Revascularization by Coronary CT Angiography using a Machine Learning Ischemia Risk Score(Springer, 2021) Kwan, Alan C.; McElhinney, Priscilla A.; Tamarappoo, Balaji K.; Cadet, Sebastien; Hurtado, Cecilia; Miller, Robert J. H.; Han, Donghee; Otaki, Yuka; Eisenberg, Evann; Ebinger, Joseph E.; Slomka, Piotr J.; Cheng, Victor Y.; Berman, Daniel S.; Dey, Damini; Radiation Oncology, School of MedicineObjectives: The machine learning ischemia risk score (ML-IRS) is a machine learning-based algorithm designed to identify hemodynamically significant coronary disease using quantitative coronary computed tomography angiography (CCTA). The purpose of this study was to examine whether the ML-IRS can predict revascularization in patients referred for invasive coronary angiography (ICA) after CCTA. Methods: This study was a post hoc analysis of a prospective dual-center registry of sequential patients undergoing CCTA followed by ICA within 3 months, referred from inpatient, outpatient, and emergency department settings (n = 352, age 63 ± 10 years, 68% male). The primary outcome was revascularization by either percutaneous coronary revascularization or coronary artery bypass grafting. Blinded readers performed semi-automated quantitative coronary plaque analysis. The ML-IRS was automatically computed. Relationships between clinical risk factors, coronary plaque features, and ML-IRS with revascularization were examined. Results: The study cohort consisted of 352 subjects with 1056 analyzable vessels. The ML-IRS ranged between 0 and 81% with a median of 18.7% (6.4-34.8). Revascularization was performed in 26% of vessels. Vessels receiving revascularization had higher ML-IRS (33.6% (21.1-55.0) versus 13.0% (4.5-29.1), p < 0.0001), as well as higher contrast density difference, and total, non-calcified, calcified, and low-density plaque burden. ML-IRS, when added to a traditional risk model based on clinical data and stenosis to predict revascularization, resulted in increased area under the curve from 0.69 (95% CI: 0.65-0.72) to 0.78 (95% CI: 0.75-0.81) (p < 0.0001), with an overall continuous net reclassification improvement of 0.636 (95% CI: 0.503-0.769; p < 0.0001). Conclusions: ML-IRS from quantitative coronary CT angiography improved the prediction of future revascularization and can potentially identify patients likely to receive revascularization if referred to cardiac catheterization. Key points: • Machine learning ischemia risk from quantitative coronary CT angiography was significantly higher in patients who received revascularization versus those who did not receive revascularization. • The machine learning ischemia risk score was significantly higher in patients with invasive fractional flow ≤ 0.8 versus those with > 0.8. • The machine learning ischemia risk score improved the prediction of future revascularization significantly when added to a standard prediction model including stenosis.Item Prognostic Value of Phase Analysis for Predicting Adverse Cardiac Events beyond Conventional SPECT Variables: Results from the REFINE SPECT Registry(American Heart Association, 2021) Kuronuma, Keiichiro; Miller, Robert J. H.; Otaki, Yuka; Van Kriekinge, Serge D.; Diniz, Marcio A.; Sharir, Tali; Hu, Lien-Hsin; Gransar, Heidi; Liang, Joanna X.; Parekh, Tejas; Kavanagh, Paul; Einstein, Andrew J.; Fish, Mathews B.; Ruddy, Terrence D.; Kaufmann, Philipp A.; Sinusas, Albert J.; Miller, Edward J.; Bateman, Timothy M.; Dorbala, Sharmila; Di Carli, Marcelo; Tamarappoo, Balaji K.; Dey, Damini; Berman, Daniel S.; Slomka, Piotr J.; Radiation Oncology, School of MedicineBackground: Phase analysis of single-photon emission computed tomography myocardial perfusion imaging provides dyssynchrony information which correlates well with assessments by echocardiography, but the independent prognostic significance is not well defined. This study assessed the independent prognostic value of single-photon emission computed tomography-myocardial perfusion imaging phase analysis in the largest multinational registry to date across all modalities. Methods: From the REFINE SPECT (Registry of Fast Myocardial Perfusion Imaging With Next Generation SPECT), a total of 19 210 patients were included (mean age 63.8±12.0 years and 56% males). Poststress total perfusion deficit, left ventricular ejection fraction, and phase variables (phase entropy, bandwidth, and SD) were obtained automatically. Cox proportional hazards analyses were performed to assess associations with major adverse cardiac events (MACE). Results: During a follow-up of 4.5±1.7 years, 2673 (13.9%) patients experienced MACE. Annualized MACE rates increased with phase variables and were ≈4-fold higher between the second and highest decile group for entropy (1.7% versus 6.7%). Optimal phase variable cutoff values stratified MACE risk in patients with normal and abnormal total perfusion deficit and left ventricular ejection fraction. Only entropy was independently associated with MACE. The addition of phase entropy significantly improved the discriminatory power for MACE prediction when added to the model with total perfusion deficit and left ventricular ejection fraction (P<0.0001). Conclusions: In a largest to date imaging study, widely representative, international cohort, phase variables were independently associated with MACE and improved risk stratification for MACE beyond the prediction by perfusion and left ventricular ejection fraction assessment alone. Phase analysis can be obtained fully automatically, without additional radiation exposure or cost to improve MACE risk prediction and, therefore, should be routinely reported for single-photon emission computed tomography-myocardial perfusion imaging studies.Item Soft tissue displacement for detection of left ventricle apical dyskinesis with transthoracic echocardiography(Springer, 2023) Schwartz, Brandon H.; Tamarappoo, Balaji K.; Shmueli, Hezzy; Siegel, Robert J.; Medicine, School of MedicineWe tested the hypothesis that the use of outward displacement of the soft tissue between the apex and the chest wall as seen in TTE, is a sign of apical displacement and would allow for more accurate diagnosis of apical dyskinesis. This is a retrospective study of 123 patients who underwent TTE and cardiac magnetic resonance imaging (MRI) within a time frame of 6 months between 2008 and 2019. 110 subjects were deemed to have good quality studies and included in the final analysis. An observer blinded to the study objectives evaluated the echocardiograms and recorded the presence or absence of apical dyskinesis. Two independent observers evaluated the echocardiograms based on the presence or absence of outward displacement of the overlying tissue at the LV apex. Cardiac MRI was used to validate the presence of apical dyskinesis. The proportion of studies which were identified as having apical dyskinesis with conventional criteria defined as outward movement of the left ventricular apex during systole were compared to those deemed to have dyskinesis based on tissue displacement. By cardiac MRI, 90 patients had apical dyskinesis. Using conventional criteria on TTE interpretation, 21 were diagnosed with apical dyskinesis (23.3%). However, when soft tissue displacement was used as the diagnostic marker of dyskinesis, 78 patients (86.7%) were diagnosed with dyskinesis, p < 0.01. Detection of displacement of soft tissue overlying the LV apex facilitates better recognition of LV apical dyskinesis.