Diagnostic safety of a machine learning-based automatic patient selection algorithm for stress-only myocardial perfusion SPECT.

BACKGROUND: Stress-only myocardial perfusion imaging (MPI) markedly reduces radiation dose, scanning time, and cost. We developed an automated clinical algorithm to safely cancel unnecessary rest imaging with high sensitivity for obstructive coronary artery disease (CAD). METHODS AND RESULTS: Patients without known CAD undergoing both MPI and invasive coronary angiography from REFINE SPECT were studied. A machine learning score (MLS) for prediction of obstructive CAD was generated using stress-only MPI and pre-test clinical variables. An MLS threshold with a pre-defined sensitivity of 95% was applied to the automated patient selection algorithm. Obstructive CAD was present in 1309/2079 (63%) patients. MLS had higher area under the receiver operator characteristic curve (AUC) for prediction of CAD than reader diagnosis and TPD (0.84 vs 0.70 vs 0.78, P < .01). An MLS threshold of 0.29 had superior sensitivity than reader diagnosis and TPD for obstructive CAD (95% vs 87% vs 87%, P < .01) and high-risk CAD, defined as stenosis of the left main, proximal left anterior descending, or triple-vessel CAD (sensitivity 96% vs 89% vs 90%, P < .01). CONCLUSIONS: The MLS is highly sensitive for prediction of both obstructive and high-risk CAD from stress-only MPI and can be applied to a stress-first protocol for automatic cancellation of unnecessary rest imaging.

Impact of Early Revascularization on Major Adverse Cardiovascular Events in Relation to Automatically Quantified Ischemia.

OBJECTIVES: 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.

5-Year Prognostic Value of Quantitative Versus Visual MPI in Subtle Perfusion Defects: Results From REFINE SPECT.

OBJECTIVES: This study compared the ability of automated myocardial perfusion imaging analysis to predict major adverse cardiac events (MACE) to that of visual analysis. BACKGROUND: Quantitative analysis has not been compared with clinical visual analysis in prognostic studies. METHODS: A total of 19,495 patients from the multicenter REFINE SPECT (REgistry of Fast Myocardial Perfusion Imaging with NExt generation SPECT) study (64 ± 12 years of age, 56% males) undergoing stress Tc-99m-labeled single-photon emission computed tomography (SPECT) myocardial perfusion imaging were followed for 4.5 ± 1.7 years for MACE. Perfusion abnormalities were assessed visually and categorized as normal, probably normal, equivocal, or abnormal. Stress total perfusion deficit (TPD), quantified automatically, was categorized as TPD = 0%, TPD >0% to <1%, ≤1% to <3%, ≤3% to <5%, ≤5% to ≤10%, or TPD >10%. MACE consisted of death, nonfatal myocardial infarction, unstable angina, or late revascularization (>90 days). Kaplan-Meier and Cox proportional hazards analyses were performed to test the performance of visual and quantitative assessments in predicting MACE. RESULTS: During follow-up examinations, 2,760 (14.2%) MACE occurred. MACE rates increased with worsening of visual assessments, that is, the rate for normal MACE was 2.0%, 3.2% for probably normal, 4.2% for equivocal, and 7.4% for abnormal (all p < 0.001). MACE rates increased with increasing stress TPD from 1.3% for the TPD category of 0% to 7.8% for the TPD category of >10% (p < 0.0001). The adjusted hazard ratio (HR) for MACE increased even in equivocal assessment (HR: 1.56; 95% confidence interval [CI]: 1.37 to 1.78) and in the TPD category of ≤3% to <5% (HR: 1.74; 95% CI: 1.41 to 2.14; all p < 0.001). The rate of MACE in patients visually assessed as normal still increased from 1.3% (TPD = 0%) to 3.4% (TPD ≥5%) (p < 0.0001). CONCLUSIONS: Quantitative analysis allows precise granular risk stratification in comparison to visual reading, even for cases with normal clinical reading.

Rationale and design of the REgistry of Fast Myocardial Perfusion Imaging with NExt generation SPECT (REFINE SPECT).

BACKGROUND: We aim to establish a multicenter registry collecting clinical, imaging, and follow-up data for patients who undergo myocardial perfusion imaging (MPI) with the latest generation SPECT scanners. METHODS: REFINE SPECT (REgistry of Fast Myocardial Perfusion Imaging with NExt generation SPECT) uses a collaborative design with multicenter contribution of clinical data and images into a comprehensive clinical-imaging database. All images are processed by quantitative software. Over 290 individual imaging variables are automatically extracted from each image dataset and merged with clinical variables. In the prognostic cohort, patient follow-up is performed for major adverse cardiac events. In the diagnostic cohort (patients with correlating invasive angiography), angiography and revascularization results within 6 months are obtained. RESULTS: To date, collected prognostic data include scans from 20,418 patients in 5 centers (57% male, 64.0 ± 12.1 years) who underwent exercise (48%) or pharmacologic stress (52%). Diagnostic data include 2079 patients in 9 centers (67% male, 64.7 ± 11.2 years) who underwent exercise (39%) or pharmacologic stress (61%). CONCLUSION: The REFINE SPECT registry will provide a resource for collaborative projects related to the latest generation SPECT-MPI. It will aid in the development of new artificial intelligence tools for automated diagnosis and prediction of prognostic outcomes.

Upper reference limits of transient ischemic dilation ratio for different protocols on new-generation cadmium zinc telluride cameras: A report from REFINE SPECT registry.

BACKGROUND: Upper reference limits for transient ischemic dilation (TID) have not been rigorously established for cadmium-zinc-telluride (CZT) camera systems. We aimed to derive TID limits for common myocardial perfusion imaging protocols utilizing a large, multicenter registry (REFINE SPECT). METHODS: One thousand six hundred and seventy-two patients with low likelihood of coronary artery disease with normal perfusion findings were identified. Images were processed with Quantitative Perfusion SPECT software (Cedars-Sinai Medical Center, Los Angeles, CA). Non-attenuation-corrected, camera-, radiotracer-, and stress protocol-specific TID limits in supine position were derived from 97.5th percentile and mean + 2 standard deviations (SD). Reference limits were compared for different solid-state cameras (D-SPECT vs. Discovery), radiotracers (technetium-99m-sestamibi vs. tetrofosmin), different types of stress (exercise vs. four different vasodilator-based protocols), and different vasodilator-based protocols. RESULTS: TID measurements did not follow Gaussian distribution in six out of eight subgroups. TID limits ranged from 1.18 to 1.52 (97.5th percentile) and 1.18 to 1.39 (mean + 2SD). No difference was noted between D-SPECT and Discovery cameras (P = 0.71) while differences between exercise and vasodilator-based protocols (adenosine, regadenoson, or regadenoson-walk) were noted (all P < 0.05). CONCLUSIONS: We used a multicenter registry to establish camera-, radiotracer-, and protocol-specific upper reference limits of TID for supine position on CZT camera systems. Reference limits did not differ between D-SPECT and Discovery camera.

Left Atrial Fibrosis and Risk of Cerebrovascular and Cardiovascular Events in Patients With Atrial Fibrillation.

BACKGROUND: Severity of left atrial (LA) fibrosis is a strong predictor of atrial fibrillation (AF) ablation success and has been associated with a history of stroke, hypertension, and heart failure (HF). However, it is unclear whether more severe LA fibrosis independently increases the risk of major adverse cardiovascular and cerebrovascular events (MACCE) among those with AF. OBJECTIVES: The goal of this study was to evaluate the occurrence and frequency of MACCE by strata of LA fibrosis severity in patients with AF. METHODS: This was a retrospective cohort study of 1,228 patients with AF who underwent late gadolinium enhancement (LGE)-cardiac magnetic resonance imaging to quantify LA fibrosis severity between January 2007 and June 2015. Patients were stratified according to Utah stage of LA LGE criteria, and observed for the occurrence of MACCE, which included a composite of stroke or transient ischemic attack (TIA), myocardial infarction, acute decompensated HF, or cardiovascular death. Disease risk score (DRS) stratification was used to control for between-group differences in baseline characteristics and risk. RESULTS: During follow-up, 62 strokes or TIAs, 42 myocardial infarctions, 156 HF events, and 38 cardiovascular deaths occurred. In DRS stratified analysis, the hazard ratio comparing patients with stage IV versus stage I LA LGE was 1.67 (95% confidence interval: 1.01 to 2.76) for the composite MACCE outcome. The only individual component of the MACCE outcome to remain significantly associated with advanced LGE following DRS stratification was stroke or TIA (hazard ratio: 3.94; 95% confidence interval: 1.72 to 8.98). CONCLUSIONS: This retrospective analysis demonstrated that more severe LA LGE is associated with increased MACCE risk, driven primarily by increased risk of stroke or TIA.

Effect of reduced cardiac output on blood stasis on transcatheter aortic valve leaflets: implications for valve thrombosis.

AIMS: There is an increasing awareness of leaflet thrombosis following transcatheter aortic valve implantation (TAVI) and valve-in-valve (ViV) procedures. Nevertheless, the predisposing factors affecting transcatheter aortic valve (TAV) thrombosis have remained unclear. This study aimed to quantify the effects of reduced cardiac output (CO) on blood stasis on the TAV leaflets as a permissive factor for valve thrombosis. METHODS AND RESULTS: An idealised computational model representing a TAV was developed in a patient-specific geometry. Three-dimensional flow fields were obtained via a fluid-solid interaction modelling approach at different COs: 5.0, 3.5, 2.0 L/min. Blood residence time (BRT) was subsequently calculated on the leaflets. An association between reduced CO and increased blood stasis on the TAV leaflets was observed. At the end of diastole, larger areas of high BRT (>1.2 s) were observed at the leaflet's fixed edge at low COs. Such areas were calculated to be 2, 8, and 11% of the total surface area of leaflets at CO=5.0, 3.5, and 2.0 L/min, respectively, indicating a ~sixfold increase of BRT on the leaflets from the highest to the lowest CO. CONCLUSIONS: This study indicates an association between reduced CO and increased blood stasis on the TAV leaflets which can be regarded as a precursor of valve thrombosis.

Blood Stasis on Transcatheter Valve Leaflets and Implications for Valve-in-Valve Leaflet Thrombosis.

BACKGROUND: Leaflet thrombosis after valve-in-valve (ViV) procedure has been increasingly recognized. This study aimed to investigate the flow dynamics aspect of leaflet thrombosis by quantifying the blood stasis on the noncoronary and coronary leaflets of a surgical aortic valve (SAV) and a transcatheter aortic valve (TAV) in a ViV setting. METHODS: Two computational models, representing a SAV and a TAV in ViV setting, were developed in a patient-specific geometry. Three-dimensional flow fields were obtained through a fluid-solid interaction modeling approach to study the difference in blood residence time (BRT) on the coronary and noncoronary leaflets. RESULTS: Longer BRT was observed on the TAV leaflets compared with the SAV, specifically near the leaflet fixed boundary. Particularly, at the end of diastole, the areas of high BRT (≥1.2 seconds) on the surface of the TAV model leaflets were four times larger than those of the SAV model. The distribution of BRT on the three leaflets exhibited a similar pattern in the model for the TAV in ViV setting. That was in contrast to the SAV model where large areas of high BRT were observed on the noncoronary leaflet. CONCLUSIONS: Geometric confinement of the TAV by the leaflets and the frame of the degenerated bioprosthesis that circumferentially surround the TAV stent increases the BRT on the leaflets, which may act as a permissive factor in the TAV leaflet thrombosis after ViV procedure. A similar distribution pattern of BRT observed on the TAV leaflets may explain the similar rate of occurrence of thrombosis on the three leaflets.