Comparison of human observer impression of X-ray fluoroscopy and angiography image quality with technical changes to image quality.

Purpose: Spatio-temporal variability in clinical fluoroscopy and cine angiography images combined with nonlinear image processing prevents the application of traditional image quality measurements in the cardiac catheterization laboratory. We aimed to develop and validate methods to measure human observer impressions of the image quality. Approach: Multi-frame images of the thorax of a euthanized pig were acquired to provide an anatomical background. The detector dose was varied from 6 to 200 nGy (increments 2×), and 0.6 and 1.0 mm focal spots were used. Two coronary stents with/without 0.5 mm separation and a synthetic right coronary artery (RCA) with hemispherical defects were embedded into the background images as test objects. The quantitative observer ( n = 17 ) performance was measured using a two-alternating forced-choice test of whether stents were separated and by a count of visible right coronary artery defects. Qualitative impressions of noise, spatial resolution, and overall image quality were measured using a visual analog scale (VAS). A paired t -test and multinomial logistic regression model were used to identify statistically significant factors affecting the observer's impression image quality. Results: The proportion of correct detection of stent separation and the number of reported right coronary artery defects changed significantly with detector dose increment in the 6 to 100 nGy ( p < 0.05 ). Although a trend favored the 0.6 versus 1.0 mm focal spot for these quantitative assessments, this was insignificant. Visual analog scale measurements changed significantly with detector dose increments in the range of 24 to 100 nGy and focal spot size ( p < 0.05 ). The application of multinomial logistic regression analysis to observer VAS scores demonstrated sensitivity matching of the paired t -test applied to quantitative observer performance measurements. Conclusions: Both quantitative and qualitative measurements of observer impression of the image quality were sensitive to image quality changes associated with changing the detector dose and focal spot size. These findings encourage future work that uses qualitative image quality measurements to assess clinical fluoroscopy and angiography image quality.

Coronary Vasomotor Dysfunction Is Associated With Cardiovascular Events in Patients With Nonobstructive Coronary Artery Disease.

BACKGROUND: Coronary vasomotor dysfunction (CVDys) can be comprehensively classified on the basis of anatomy and functional mechanisms. OBJECTIVES: The aim of this study was to evaluate the association between different CVDys phenotypes and outcomes in patients with angina and nonobstructive coronary artery disease (ANOCA). METHODS: Patients with ANOCA who underwent coronary reactivity testing using an intracoronary Doppler guidewire to assess microvascular and epicardial coronary endothelium-dependent and endothelium-independent function were enrolled. Endothelium-dependent microvascular and epicardial coronary dysfunction were defined as a <50% change in coronary blood flow in response to intracoronary acetylcholine (Ach) infusion and a <-20% change in coronary artery diameter in response to Ach. Endothelium-independent microvascular and epicardial coronary dysfunction were defined as coronary flow reserve < 2.5 during adenosine-induced hyperemia and change in cross-sectional area in response to intracoronary nitroglycerin administration < 20%. Major adverse cardiac and cerebrovascular events (cardiovascular death, nonfatal MI, heart failure, stroke, and late revascularization) served as clinical outcomes. RESULTS: Among the 1,196 patients with ANOCA, the prevalence of CVDys was 24.5% and 51.8% among those with endothelium-independent and endothelium-dependent microvascular dysfunction, respectively, and 47.4% and 25.4% among those with endothelium-independent and endothelium-dependent epicardial coronary dysfunction, respectively. During 6.3 years (Q1-Q3: 2.5-12.9 years) of follow-up, patients with endothelium-dependent microvascular dysfunction, endothelium-dependent epicardial coronary dysfunction, or endothelium-independent microvascular dysfunction showed significantly higher event rates compared with those without (19.5% vs 12.0% [P < 0.001], 19.7% vs 14.6% [P = 0.038] and 22.2% vs 13.8% [P = 0.001], respectively). Coronary flow reserve (HR: 0.757; 95% CI: 0.604-0.957) and percentage change in coronary blood flow in response to Ach infusion (HR: 0.998; 95% CI: 0.996-0.999) remained significant predictors of major adverse cardiac and cerebrovascular event after adjustment for conventional risk factors. CONCLUSIONS: CVDys phenotype is differentially associated with worse outcomes, and endothelium-dependent and endothelium-independent microvascular function provide independent prognostic information in patients with ANOCA.

Prognostic Implications of Resistive Reserve Ratio in Patients With Nonobstructive Coronary Artery Disease With Myocardial Bridging.

BACKGROUND: Myocardial bridging (MB) is accompanied by the dynamic extravascular compression of epicardial coronary arteries, leading to intracoronary hemodynamic disturbance with abnormal coronary flow profiles. We aimed to evaluate the prognostic implications of resistive reserve ratio (RRR), a composite measure of flow and pressure parameters that represents the vasodilatory capacity of the coronary arteries, in patients with angina with nonobstructive coronary artery disease (ANOCA) and MB, in comparison with coronary flow reserve (CFR). METHODS AND RESULTS: In this retrospective cohort study, we included patients with ANOCA who underwent coronary reactivity testing, where MB was identified by transient constriction in coronary artery segments between systole and diastole. Abnormal CFR and RRR were defined as <2.5 and <2.62, respectively. Major adverse cardiac events, including cardiovascular death, stroke, myocardial infarction, heart failure, and late revascularization, served as outcomes. Among 1251 patients with ANOCA, 191 (15.3%) had MB. The prevalence of abnormal CFR or RRR was not significantly different between patients with and without MB (P=0.144 and P=0.398, respectively). Over a median follow-up time of 6.9 years, abnormal RRR predicted major adverse cardiac events in patients with MB (hazard ratio [HR], 4.38 [95% CI, 1.71-11.21]; P=0.002) and without MB (HR, 1.91 [95% CI, 1.38-2.64]; P<0.001). Abnormal CFR predicted major adverse cardiac events in patients without MB (HR, 2.15 [95% CI, 1.54-3.00]; P<0.001), whereas it was not predictive of major adverse cardiac events in patients with MB (HR, 2.29 [95% CI, 0.93-5.65]; P=0.073). CONCLUSIONS: In patients with ANOCA and MB, impaired RRR was superior to impaired CFR in distinguishing patients at a higher risk of future adverse events, suggesting that RRR may serve as a risk stratification tool in patients with MB and ANOCA.

Predictive Value of Artificial Intelligence-Enabled Electrocardiography in Patients With Takotsubo Cardiomyopathy.

BACKGROUND: Recent studies have indicated high rates of future major adverse cardiovascular events in patients with Takotsubo cardiomyopathy (TC), but there is no well-established tool for risk stratification. This study sought to evaluate the prognostic value of several artificial intelligence-augmented ECG (AI-ECG) algorithms in patients with TC. METHODS AND RESULTS: This study examined consecutive patients in the prospective and observational Mayo Clinic Takotsubo syndrome registry. Several previously validated AI-ECG algorithms were used for the estimation of ECG- age, probability of low ejection fraction, and probability of atrial fibrillation. Multivariable models were constructed to evaluate the association of AI-ECG and other clinical characteristics with major adverse cardiac events, defined as cardiovascular death, recurrence of TC, nonfatal myocardial infarction, hospitalization for congestive heart failure, and stroke. In the final analysis, 305 patients with TC were studied over a median follow-up of 4.8 years. Patients with future major adverse cardiac events were more likely to be older, have a history of hypertension, congestive heart failure, worse renal function, as well as high-risk AI-ECG findings compared with those without. Multivariable Cox proportional hazards analysis indicated that the presence of 2 or 3 high-risk findings detected by AI-ECG remained a significant predictor of major adverse cardiac events in patients with TC after adjustment by conventional risk factors (hazard ratio, 4.419 [95% CI, 1.833-10.66], P=0.001). CONCLUSIONS: The combined use of AI-ECG algorithms derived from a single 12-lead ECG might detect subtle underlying patterns associated with worse outcomes in patients with TC. This approach might be beneficial for stratifying high-risk patients with TC.

Combined Assessment of Fractional Flow Reserve and Coronary Flow Velocity Reserve after Drug-Eluting Stent Implantation.

BACKGROUND: Coronary flow velocity reserve (CFVR) can be measured noninvasively using stress transthoracic Doppler echocardiography (S-TDE). The prognostic significance of S-TDE-derived CFVR after percutaneous coronary intervention (PCI) remains unknown. The aim of this study was to investigate the prognostic value of post-PCI CFVR and its additional efficacy to fractional flow reserve (FFR) in patients undergoing elective PCI. METHODS: A retrospective study was conducted involving 187 consecutive patients with chronic coronary syndrome who underwent elective PCI guided by FFR for the left anterior descending coronary artery. Pre- and post-PCI wire-based FFR and CFVR assessments of the left anterior descending coronary artery using S-TDE were performed in all patients. The association between post-PCI clinical and physiologic parameters and major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, heart failure, and unplanned remote target vessel revascularization, was evaluated. RESULTS: Three-quarters of patients exhibited CFVR increase after PCI, while all patients showed FFR improvement. During a median follow-up period of 1.5 years, MACE occurred in 21 patients (11.2%). Among clinical demographics, patients with MACE had higher levels of N-terminal pro-brain natriuretic peptide compared with those without MACE (median, 615 pg/mL [interquartile range, 245-1,500 pg/mL] vs 180 pg/mL [interquartile range, 70-559 pg/mL]; P = .010). Post-PCI S-TDE-derived CFVR was lower in patients with MACE, while post-PCI FFR showed a nonsignificant tendency to be lower in patients with MACE. In a multivariable analysis, higher NT-proBNP (adjusted hazard ratio, 1.33; 95% CI, 1.02-1.74; P = .038), post-PCI CFVR ≤ 2.0 (adjusted hazard ratio, 2.93; 95% CI, 1.16-7.40; P = .023), and post-PCI FFR ≤ 0.82 (adjusted hazard ratio, 3.93; 95% CI, 1.52-10.18; P = .005) were independently associated with MACE. CONCLUSIONS: In patients with chronic coronary syndrome who underwent successful elective PCI for left anterior descending coronary artery, the combined assessment of S-TDE-derived post-PCI CFVR and post-PCI FFR provided a significant association with the occurrence of MACE.

Predictors and Prognostic value of Coronary Computed Tomography Angiography for Unrecognized Myocardial Infarction in Patients with Chronic Coronary Syndrome.

BACKGROUND: Unrecognized myocardial infarction (UMI) on delayed-enhancement cardiac magnetic resonance imaging (DE-CMR) and coronary computed tomography angiography (CCTA) derived high-risk features provide prognostic information in patients with chronic coronary syndrome (CCS). The study aimed to assess the prognostic value of UMI and predictors of UMI using CCTA in patients with CCS undergoing elective percutaneous coronary intervention (PCI). METHODS: This study enrolled 181 CCS patients underwent both DE-CMR and CCTA before elective PCI. The CCTA-derived predictors of UMI and the association of baseline clinical characteristics, CCTA findings, and CMR-derived factors including UMI with MACE, defined as death, nonfatal myocardial infarction, unplanned late revascularization, hospitalization for congestive heart failure, and stroke were investigated. RESULTS: UMI was detected in 57 patients (31.5%). ROC analysis revealed the optimal cut-off values of Agatston score and mean pericoronary fat attenuation index (FAI) for predicting the presence of UMI were 397 and -69.8, respectively. Multivariable logistic regression analysis revealed that left ventricular mass, Agatston score >397, mean FAI >-69.8, positive remodeling of the target lesion, and CCTA-derived stenosis severity were independent predictors of UMI. Kaplan-Meier analysis revealed that patients with UMI were associated with increased risk of MACE. Cox's proportional hazards analysis showed post-PCI minimum lumen diameter and the presence of UMI were independent predictors of MACE. The risk of MACE significantly increased according to the number of 4 preprocedural CCTA relevant features of UMI. CONCLUSION: Preprocedural comprehensive CCTA analysis may help predict the presence of UMI and provide prognostic information in patients with CCS undergoing PCI.

Prognostic Value of Integrated Assessment of Cardiac Magnetic Resonance-Derived Global Coronary Flow Reserve and Cardiopulmonary Exercise Testing-Derived Peak Oxygen Consumption in Patients With Acute Myocardial Infarction.

Background: This study investigated the prognostic value of cardiovascular magnetic resonance (CMR)-derived global coronary flow reserve (G-CFR) in addition to cardiopulmonary exercise testing (CPET) variables in patients with acute myocardial infarction (AMI). Methods and Results: We investigated 127 patients with AMI who underwent primary or urgent percutaneous coronary intervention (PCI) and post-intervention CMR and CPET. The incidence of major cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent non-fatal myocardial infarction, re-hospitalization due to congestive heart failure, and stroke, was evaluated (median follow-up, 2.8 years). Patients with MACCE (n=14) had lower ejection fraction (EF) (50 [43-59] vs. 58 [51-63]%; P=0.014), lower G-CFR (1.74 [1.19-2.20] vs. 2.40 [1.61-3.66]; P=0.008), and lower peak oxygen consumption (V̇O2) (15.16±2.64 vs. 17.19±3.70 mL/kg/min; P=0.049) than patients without MACCE. G-CFR<2.33 and peak V̇O2 <15.65 mL/kg/min (cut-off values derived from receiver operating characteristic curve analyses) were significantly associated with the incidence of MACCE (log-rank test, P=0.01). The combination of low G-CFR and low peak V̇O2 improved risk discrimination for MACCE when added to the reference clinical model including age, male sex, post-PCI peak creatine kinase, EF, and left anterior descending artery culprit lesion. Conclusions: G-CFR and peak V̇O2 showed incremental prognostic information compared with the reference model using historically important clinical risk factors, indicating that this approach may help identify high-risk patients who suffer subsequent adverse events.

Association between optical coherence tomography-defined culprit morphologies and changes in hyperemic coronary flow after elective stenting assessed by transthoracic Doppler echocardiography.

BACKGROUND: Stress-transthoracic Doppler echocardiography (S-TDE) provides a noninvasive assessment of coronary flow parameters in the left anterior descending artery (LAD). However, the association between morphological characteristics and coronary flow changes after elective percutaneous coronary intervention (PCI) remains unclear. We aimed to evaluate the relationships between periprocedural coronary flow changes observed on S-TDE and lesion-specific plaque characteristics obtained by optical coherence tomography (OCT) in the interrogated vessels in patients with chronic coronary syndrome (CCS). METHODS AND RESULTS: Patients with CCS who underwent pre- and post-PCI S-TDE and elective fractional flow reserve (FFR)-guided PCI under OCT guidance for de novo single LAD lesions were included. S-TDE-derived hyperemic diastolic peak flow velocity (hDPV) was used as a surrogate for coronary flow. Lesions were categorized into two groups based on the %hDPV increase or decrease. The baseline clinical, physiological, and OCT findings were compared between the groups. In total, 103 LAD lesions were studied in 103 patients. After PCI, hDPV significantly increased from 55.6 cm/s to 69.5 cm/s (P<0.01), with a median %hDPV increase of 27.2 (6.32-59.1) %, while %hDPV decreased in 20 (19.4%) patients. The FFR improved in all patients. On OCT, layered plaques were more frequently present in the culprit vessels in the %hDPV-decrease group than in the %hDPV-increase group (85.0% vs. 50.6%, P = 0.01). Multivariable logistic regression analysis showed that the presence of layered plaques and high pre-PCI hDPV were independent predictors of %hDPV decrease. CONCLUSIONS: In patients who underwent successful uncomplicated elective PCI for de novo single LAD lesions, the presence of layered plaques was independently associated with hyperemic coronary flow decrease as assessed by S-TDE.

Noninvasive transthoracic doppler flow velocity and invasive thermodilution to assess coronary flow reserve.

Background: Coronary flow reserve (CFR) provides prognostication and coronary physiological information, including epicardial coronary stenosis and microvascular function. The relationship between stress transthoracic Doppler echocardiography (TDE)-derived coronary flow velocity reserve (CFRS-TDE) and thermodilution-derived coronary flow reserve (CFRthermo) before and after elective percutaneous coronary intervention (PCI) remains unclear. Methods: This single-center prospective registry study evaluated patients who underwent fractional flow reserve (FFR)-guided elective PCI for left anterior descending artery (LAD) lesions with wire-based invasive physiological measurements and pre- and post-PCI stress TDE examinations. Results: A total of 174 LAD lesions from 174 patients were included in the final analysis. A modest correlation was detected between the pre-PCI CFRS-TDE and the pre-PCI CFRthermo (r=0.383, P<0.001). The frequently used CFRS-TDE threshold of 2.0 corresponded to a pre-PCI CFRthermo of 2.18. Pre-PCI CFRS-TDE underestimated pre-PCI CFRthermo [1.89 (1.44-2.31) vs. 2.05 (1.38-2.93), P<0.001]. Both CFRS-TDE and CFRthermo increased significantly post-PCI [pre-PCI CFRS-TDE 1.89 vs. post-PCI CFRS-TDE 2.33, P<0.001; pre-PCI CFRthermo 2.05 (1.38-2.93) vs. post-PCI CFRthermo 2.59 (1.63-3.55), P<0.001]. In contrast, there was no significant relationship between changes in CFRS-TDE and changes in CFRthermo after PCI (r=0.008, P=0.915) or between post-PCI CFRS-TDE and post-PCI CFRthermo (r=0.054, P=0.482). Conclusions: Pre-PCI CFRS-TDE and CFRthermo are modestly correlated, but post-PCI CFRS-TDE and CFRthermo have no correlation. CFRS-TDE and CFRthermo are not interchangeable, particularly post-PCI, suggesting that the two metrics represent different coronary physiologies after PCI.

Angiographic Findings and Post-Percutaneous Coronary Intervention Fractional Flow Reserve.

Importance: The associations between angiographic findings and post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) and their clinical relevance according to residual functional disease burden have not been thoroughly investigated. Objectives: To evaluate the association of angiographic and physiologic parameters according to residual functional disease burden after drug-eluting stent implantation. Design, Setting, and Participants: This cohort study population was from the International Post-PCI FFR registry, which incorporated 4 registries from Korea, China, and Japan. Patients who underwent angiographically successful second-generation drug-eluting stent implantation and post-PCI FFR measurement were included in the analysis. The patients were divided into 3 groups according to the residual disease burden (post-PCI FFR ≤0.80 [residual ischemia], 0.81-0.86 [suboptimal], and >0.86 [optimal]). The data were collected from August 23, 2018, to June 11, 2019, and the current analysis was performed from January 11, 2022, to October 7, 2023. Exposures: Angiographic parameters and post-PCI FFR. Main Outcomes and Measures: The primary outcome was target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction, and target vessel revascularization (TVR) at 2 years. Results: In this cohort of 2147 patients, the mean (SD) age was 64.3 (10.0) years, and 1644 patients (76.6%) were men. Based on the post-PCI physiologic status, 269 patients (12.5%) had residual ischemia, 551 (25.7%) had suboptimal results, and 1327 (61.8%) had optimal results. Angiographic parameters had poor correlations with post-PCI FFR (r < 0.20). Post-PCI FFR was isolated from all angiographic parameters in the unsupervised hierarchical cluster analysis. Post-PCI FFR was associated with the occurrence of TVF (adjusted hazard ratio [AHR] per post-PCI FFR 0.01 increase, 0.94 [95% CI, 0.92-0.97]; P < .001), but angiographic parameters were not. The residual ischemia group had a significantly higher rate of TVF than the suboptimal group (AHR, 1.75 [95% CI, 1.08-2.83]; P = .02) and the optimal group (AHR, 2.94 [95% CI, 1.82-4.73]; P < .001). The TVR in the residual ischemia group was predominantly associated with TVR in the nonstented segment (14 [53.8%]), unlike the other 2 groups (3 [10.0%] in the suboptimal group and 13 [30.2%] in the optimal group). Conclusions and Relevance: In this cohort study of the International Post-PCI FFR registry, a low degree of associations were observed between angiographic and physiologic parameters after PCI. Post-PCI FFR, unlike angiographic parameters, was associated with clinical events and the distribution of clinical events. The current study supports the use of post-PCI FFR as a procedural quality metric and further prospective study is warranted.

Diagnostic value of computed tomography myocardial perfusion imaging to detect coexisting microvascular dysfunction in patients with obstructive epicardial coronary artery disease.

Background: Computed tomography myocardial perfusion (CT-MP) has reported usefulness in assessing hemodynamically significant epicardial coronary artery lesions. However, the diagnostic ability of the absolute coronary flow using CT-MP to detect coronary microvascular dysfunction (CMD) remains elusive. This prospective cohort study aimed to assess the diagnostic value of CT-MP in evaluating coexisting CMD in patients with functionally significant epicardial coronary stenosis and to analyze the predictive factors of lesions with CMD. Methods: Sixty-eight patients with chronic coronary syndrome (CCS) and de novo single functionally significant stenosis [fractional flow reserve (FFR) ≤0.80] were studied. CMD was defined as an index of microcirculatory resistance ≥25. We compare clinical background and CT-MP findings between patients with and without CMD (CMD, n=29; non-CMD, n=39). CT-MP, and quantitative and qualitative plaque assessments were included in computed tomography angiography assessment. Logistic regression analysis was performed to predict CMD. Results: FFR, invasive wire-derived coronary flow reserve (CFRwire) and index of microcirculatory resistance were 0.68 [interquartile range (IQR), 0.59-0.74], 1.71 (IQR, 1.24-2.88), and 22.6 (IQR, 15.1-34.5), respectively. The rest and hyperemic-myocardial blood flow (MBF) and CT-MP-derived CFR (CFRCT-MP) were 0.83 (0.64-1.03) mL/min/g, 2.14 (1.30-2.92) mL/min/g, and 2.19 (1.44-3.37), respectively. In the territories with CMD, hyperemic-MBF was significantly lower than in those without [1.68 (IQR, 0.84-2.44) vs. 2.31 (IQR, 1.67-3.34) mL/min/g, P=0.015] and the prevalence of CFRCT-MP <2.0 was higher in the lesions with CMD than in those without (62.1% vs. 28.2%, P=0.011), while FFR values were similar. Fibrofatty and necrotic core component volume was greater in the vessels with CMD than in those without [31.8 (IQR, 19.0-48.9) vs. 25.1 (IQR, 17.2-32.1) mm3, P=0.045]. Multivariable logistic regression analysis showed that hyperemic-MBF and fibrofatty and necrotic core component volume were independent predictors of CMD territories [odds ratio (OR) =0.583; 95% confidence interval (CI): 0.355-0.958; P=0.033 and OR =1.040; 95% CI: 1.010-1.070; P=0.011]. Conclusions: Quantitative assessment of absolute coronary flow using pre-percutaneous coronary intervention (PCI) CT-MP, and comprehensive plaque analysis using computed tomography angiography may help detect coexisting subtended microvascular dysfunction in territories with functionally significant epicardial coronary lesions. Further studies are required to elucidate the clinical significance of coexisting CMD in patients with CCS undergoing PCI.