Prognostic implications of pre-transcatheter aortic valve replacement computed tomography-derived coronary plaque characteristics and stenosis severity.

OBJECTIVES: The study aimed to investigate the prognostic value of pre-transcatheter aortic valve replacement (TAVR) computed tomography angiography (CTA) in assessing physiological stenosis severity (CTA-derived fractional flow reserve (CT-FFR)) and high-risk plaque characteristics (HRPC). MATERIALS AND METHODS: Among TAVR patients who underwent pre-procedure CTA, the presence and number of HRPCs (minimum lumen area of < 4 mm2, plaque burden ≥ 70%, low-attenuating plaques, positive remodeling, napkin-ring sign, or spotty calcification) as well as CT-FFR were assessed. The risk of vessel-oriented composite outcome (VOCO, a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death) was compared according to the number of HRPC and CT-FFR categories. RESULTS: Four hundred and twenty-seven patients (68.4% were male) with 1072 vessels were included. Their mean age was 70.6 ± 10.6 years. Vessels with low CT-FFR (≤ 0.80) (41.7% vs. 15.8%, adjusted hazard ratio (HRadj) 1.96; 95% confidence interval (CI): 1.28-2.96; p = 0.001) or lesions with ≥ 3 HRPC (38.7% vs. 16.0%, HRadj 1.81; 95%CI 1.20-2.71; p = 0.005) demonstrated higher VOCO risk. In the CT-FFR (> 0.80) group, lesions with ≥ 3 HRPC showed a significantly higher risk of VOCO than those with < 3 HRPC (34.7% vs. 13.0%; HRadj 2.04; 95%CI 1.18-3.52; p = 0.011). However, this relative increase in risk was not observed in vessels with positive CT-FFR (≤ 0.80). CONCLUSIONS: In TAVR candidates, both CT-FFR and the presence of ≥ 3 HRPC were associated with an increased risk of adverse clinical events. However, the value of HRPC differed with the CT-FFR category, with more incremental predictability among vessels with negative CT-FFR but not among vessels with positive CT-FFR. CLINICAL RELEVANCE STATEMENT: In transcatheter aortic valve replacement (TAVR) candidates, pre-TAVR CTA provided the opportunity to assess coronary physiological stenosis severity and high-risk plaque characteristics, both of which are associated with worse clinical outcomes. KEY POINTS: • The current study investigated the prognostic value of coronary physiology significance and plaque characteristics in transcatheter aortic valve replacement patients. • The combination of coronary plaque vulnerability and physiological significance showed improved accuracy in predicting clinical outcomes in transcatheter aortic valve replacement patients. • Pre-transcatheter aortic valve replacement CT can be a one-stop-shop tool for coronary assessments in clinical practice.

Sex Differences in Coronary Inflammation and Atherosclerosis Phenotypes in Response to Imaging Marker of Stress-Related Neural Activity.

BACKGROUND: Sex-specific differences in coronary phenotypes in response to stress have not been elucidated. This study investigated the sex-specific differences in the coronary computed tomography angiography-assessed coronary response to mental stress. METHODS: This retrospective study included patients with coronary artery disease and without cancer who underwent resting 18F-fluorodexoyglucose positron emission tomography/computed tomography and coronary computed tomography angiography within 3 months. 18F-flourodeoxyglucose resting amygdalar uptake, an imaging biomarker of stress-related neural activity, coronary inflammation (fat attenuation index), and high-risk plaque characteristics were assessed by coronary computed tomography angiography. Their correlation and prognostic values were assessed according to sex. RESULTS: A total of 364 participants (27.7% women and 72.3% men) were enrolled. Among those with heightened stress-related neural activity, women were more likely to have a higher fat attenuation index (43.0% versus 24.0%; P=0.004), while men had a higher frequency of high-risk plaques (53.7% versus 39.3%; P=0.036). High amygdalar 18F-flourodeoxyglucose uptake (B-coefficient [SE], 3.62 [0.21]; P<0.001) was selected as the strongest predictor of fat attenuation index in a fully adjusted linear regression model in women, and the first-order interaction term consisting of sex and stress-related neural activity was significant (P<0.001). Those with enhanced imaging biomarkers of stress-related neural activity showed increased risk of major adverse cardiovascular event both in women (24.5% versus 5.1%; adjusted hazard ratio, 3.62 [95% CI, 1.14-17.14]; P=0.039) and men (17.2% versus 6.9%; adjusted hazard ratio, 2.72 [95% CI, 1.10-6.69]; P=0.030). CONCLUSIONS: Imaging-assessed stress-related neural activity carried prognostic values irrespective of sex; however, a sex-specific mechanism linking psychological stress to coronary plaque phenotypes existed in the current hypothesis-generating study. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05545618.

Comparison of CT-derived Plaque Characteristic Index With CMR Perfusion for Ischemia Diagnosis in Stable CAD.

BACKGROUND: Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) have been used to diagnose lesion-specific ischemia in patients with coronary artery disease. The aim of this study was to investigate the diagnostic performance of CCTA-derived plaque characteristic index compared with myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) derived from CMR perfusion in the assessment of lesion-specific ischemia. METHODS: Between October 2020 and March 2022, consecutive patients with suspected or known coronary artery disease, who were clinically referred for invasive coronary angiography were prospectively enrolled. All participants sequentially underwent CCTA and CMR and invasive fractional flow reserve within 2 weeks. The diagnostic performance of CCTA-derived plaque characteristics, CMR perfusion-derived stress MBF, and MPR were compared. Lesions with fractional flow reserve ≤0.80 were considered to be hemodynamically significant stenosis. RESULTS: Nighty-two patients with 141 vessels were included in this study. Plaque length, minimum luminal area, plaque area, percent area stenosis, total atheroma volume, vessel volume, lipid-rich volume, spotty calcium, napkin-ring signs, stress MBF, and MPR in flow-limiting stenosis group were significantly different from nonflow-limiting group. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of lesion-specific ischemia diagnosis were 61.0%, 55.3%, 63.1%, 35.6%, and 79.3% for stress MBF, and 89.4%, 89.5%, 89.3%, 75.6%, 95.8% for MPR; meanwhile, 82.3%, 79.0%, 84.5%, 65.2%, and 91.6% for CCTA-derived plaque characteristic index. CONCLUSIONS: In our prospective study, CCTA-derived plaque characteristics and MPR derived from CMR performed well in diagnosing lesion-specific myocardial ischemia and were significantly better than stress MBF in stable coronary artery disease.

Unwavering excellence: How to be a competent cardiovascular doctor in "panvascular medicine +".

It is essential to create a sustainable and all-encompassing panvascular ecosystem that integrates medical care, industry-academia research, prevention, and management, necessitating the in-depth participation of every cardiovascular doctor on their journey of unwavering excellence. "From doctors, by researchers/engineers, for patients" is the foundation of sustainable development in the "panvascular medicine +" ecosystem. Medical education can make knowledge tangible and serve as a conduit for inheritance and innovation. Prevention covers intelligent decision-making, primary prevention, and the popularization of knowledge. Furthermore, management is a potent tool for promoting development through overall coordination with social governance. Thus, in the "panvascular medicine +" ecosystem, cardiovascular doctors need to prioritize the doctor-patient collaboration, serving patients while possessing capabilities in scientific research, engineering applications, education, prevention, and management. This enables them to promote comprehensive and lifelong health management for patients.

Association of nocturnal sleep duration and nocturnal sleep changes with instrumental activities of daily living disability among middle-aged and elderly Chinese.

OBJECTIVE: To investigate the association of baseline nocturnal sleep duration and sleep changes with functional disability in middle-aged and elderly Chinese. METHODS: Data for this study were collected from the China Health and Retirement Longitudinal Study (CHARLS) from baseline (2011) to the Wave 3 follow-up (2018). 8361 participants free of IADL disability in 2011 and aged ≥ 45 years old were recruited and prospectively followed till 2018 to analyze the association between baseline nocturnal sleep duration and IADL disability. Of these 8361 participants, a total of 6948 participants had no IADL disability at the first three follow-up visits and completed the 2018 follow-up to analyze the association between nocturnal sleep changes and IADL disability. Nocturnal sleep duration (hours) was self-reported at baseline. The coefficient of variation (CV) of nocturnal sleep duration at baseline and three follow-up visits was used to calculate sleep changes and classified into mild, moderate, and severe degrees by the quantiles. Cox proportional hazards regression model was used to analyze the association of baseline nocturnal sleep duration with IADL disability, and the binary logistic regression model was used to analyze the association of nocturnal sleep changes with IADL disability. RESULTS: Among the 8361 participants of 50237.5 person-years follow-up with a median follow-up of 7 years, 2158 (25.81%) participants developed IADL disabilities. Higher risks of IADL disability were observed among participants with sleep duration <7 h [HR(95%): 1.23(1.09-1.38)], 8∼<9 h [HR(95%): 1.05(1.00-1.32)] and ≥9 h [HR(95%): 1.21(1.01-1.45)] compared to those with 7∼<8 h. Among the 6948 participants, a total of 745 (10.72%) participants finally developed IADL disabilities. Compared with mild nocturnal sleep changes, moderate [OR(95%): 1.48(1.19-1.84)] and severe [OR(95%): 2.43(1.98-3.00)] sleep changes increased the probability of IADL disability. The restricted cubic spline model showed that a higher degree of nocturnal sleep changes was associated with a greater probability of IADL disability. CONCLUSION: Both insufficient and excessive nocturnal sleep duration were associated with higher risk of IADL disability in middle-aged and elderly adults, independent of the participants' gender, age, and napping habits. Higher nocturnal sleep changes were associated with a higher probability of disability in IADL. These findings highlight the importance of appropriate and stable nocturnal sleep, and the need to pay attention to population differences in the impact of nocturnal sleep duration on health.

Stress-Related Neural Activity Associates With Coronary Plaque Vulnerability and Subsequent Cardiovascular Events.

BACKGROUND: Stress-related neural activity (SNA) assessed by amygdalar activity can predict cardiovascular events. However, its mechanistic linkage with plaque vulnerability is not fully elucidated. OBJECTIVES: The authors aimed to investigate the association of SNA with coronary plaque morphologic and inflammatory features as well as their ability in predicting major adverse cardiovascular events (MACE). METHODS: A total of 299 patients with coronary artery disease (CAD) and without cancer underwent 18F-fluorodexoyglucose positron emission tomography/computed tomography (PET/CT) and available coronary computed tomographic angiography (CCTA) between January 1, 2013, and December 31, 2020. SNA and bone-marrow activity (BMA) were assessed with validated methods. Coronary inflammation (fat attenuation index [FAI]) and high-risk plaque (HRP) characteristics were assessed by CCTA. Relations between these features were analyzed. Relations between SNA and MACE were assessed with Cox models, log-rank tests, and mediation (path) analyses. RESULTS: SNA was significant correlated with BMA (r = 0.39; P < 0.001) and FAI (r = 0.49; P < 0.001). Patients with heightened SNA are more likely to have HRP (40.7% vs 23.5%; P = 0.002) and increase risk of MACE (17.2% vs 5.1%, adjusted HR 3.22; 95% CI: 1.31-7.93; P = 0.011). Mediation analysis suggested that higher SNA associates with MACE via a serial mechanism involving BMA, FAI, and HRP. CONCLUSIONS: SNA is significantly correlated with FAI and HRP in patients with CAD. Furthermore, such neural activity was associated with MACE, which was mediated in part by leukopoietic activity in the bone marrow, coronary inflammation, and plaque vulnerability.

Association of Self-Reported Nighttime Sleep Duration with Chronic Kidney Disease: China Health and Retirement Longitudinal Study.

INTRODUCTION: The cohort study aimed to assess the association of nighttime sleep duration and the change in nighttime sleep duration with chronic kidney disease (CKD) and whether the association between nighttime sleep duration and CKD differed by daytime napping. METHODS: This study included 11,677 individuals from the China Health and Retirement Longitudinal Study (CHARLS) and used data from the 2011 baseline survey and four follow-up waves. Nighttime sleep duration was divided into three groups: short (<7 h per night), optimal (7-9 h), and long nighttime sleep duration (>9 h). Daytime napping was divided into two groups: no nap and with a nap. We used Cox proportional hazards model to examine the effect of nighttime sleep duration at baseline and change in nighttime sleep duration on incident CKD and a joint effect of nighttime sleep duration and nap time on onset CKD. RESULTS: With a follow-up of 7 years, the incidence of CKD among those with short, optimal, and long nighttime sleep duration was 9.89, 6.75, and 9.05 per 1,000 person-years, respectively. Compared to individuals with optimal nighttime sleep duration, short nighttime sleepers had a 44% higher risk of onset CKD (hazard ratio [HR]: 1.44, 95% confidence interval [CI]: 1.21-1.72). Compared to participants with persistent optimal nighttime sleep duration, those with persistent short or long nighttime sleep duration had an increased risk of incident CKD (HR: 1.44, 95% CI: 1.15-1.80). We found a lower incidence of CKD in participants with short nighttime sleep duration and a nap (HR: 0.74, 95% CI: 0.60-0.93), compared to those with short nighttime sleep duration and no nap. CONCLUSION: Short nighttime sleep duration and persistent long or short nighttime sleep duration were associated with a higher risk of onset CKD. Keeping persistent optimal nighttime sleep duration may help reduce CKD risk later in life. Daytime napping may be protective against CKD incidence.

Association of nocturnal sleep duration and midday napping with subjective poor hearing among middle-aged and older adults in China.

Background: Hearing loss has occurred as a critical concern for aging and health. However, it remains unknown whether nocturnal sleep and midday napping duration are associated with hearing loss in middle-aged and older adults. Methods: The study comprised 9,573 adults from China Health and Retirement Longitudinal Study, who have completed the survey for sleep characteristics and subjective functional hearing. We collected self-reported nocturnal sleep duration (<5, 5 to <6, 6 to <7, 7 to <9, ≥9 h/night) and midday napping duration (≤5, 5 to ≤30, and >30 min). The sleep information was classified into different sleep patterns. The primary outcome was self-reported hearing loss events. Multivariate Cox regression models and restricted cubic splines were used to investigate the longitudinal association of sleep characteristics with hearing loss. We applied Cox generalized additive models and bivariate exposure-response surface diagrams to visualize the effects of different sleep patterns on hearing loss. Results: We confirmed 1,073 cases of hearing loss (55.1% female) during the follow-up. After adjusting for demographic characteristics, lifestyle factors and health condition, nocturnal sleep with < 5 h was positively associated with hearing loss [hazard ratio (HR): 1.45, 95% confidence interval [CI]: 1.20, 1.75]. Individuals with napping for 5 to ≤30 min had a 20% (HR: 0.80, 95%CI: 0.63, 1.00) lower risk of hearing loss compared with those with napping ≤ 5 min. Restrictive cubic splines showed the reverse J-shaped association between nocturnal sleep and hearing loss. Moreover, we found significant joint effects of sleeping < 7 h/night and midday napping ≤ 5 min (HR: 1.27, 95% CI: 1.06, 1.52) on hearing loss. Bivariate exposure-response surface diagrams also reflected the finding that short sleep without napping existed the highest risk of hearing loss. Compared with persistently sleeping moderately (7-9 h/night), those who persistently slept < 7 h/night or shifted from < 7 h/night to moderate or > 9 h/night had higher risks of hearing loss. Conclusion: Inadequate nocturnal sleep was associated with an elevated risk of poor subjective hearing in middle-aged and older adults, while moderate napping decreased the risk of hearing loss. Keeping sleep stable within recommendation duration may be a useful strategy for preventing poor hearing loss.

Quantitative flow ratio derived pullback pressure gradient and CZT-SPECT measured longitudinal flow gradient for hemodynamically significant coronary artery disease.

BACKGROUND: Whether physiological coronary diffuseness assessed by quantitative flow reserve (QFR) pullback pressure gradient (PPG) correlates with longitudinal myocardial blood flow (MBF) gradient and improves diagnostic performances for myocardial ischemia remains unknown. METHODS AND RESULTS: MBF was measured in mL g-1 min-1 with 99mTc-MIBI CZT-SPECT at rest and stress, corresponding myocardial flow reserve (MFR = MBF stress/MBF rest) and relative flow reserve (RFR = MBF stenotic area/MBF reference) were calculated. Longitudinal MBF gradient was defined as apical and basal left ventricle MBF gradient. △longitudinal MBF gradient was calculated by longitudinal MBF gradient at stress and rest. QFR-PPG was acquired from virtual QFR pullback curve. QFR-PPG significantly correlated with hyperemic longitudinal MBF gradient (r = 0.45, P = 0.007) and △longitudinal MBF gradient (stress-rest) (r = 0.41, P = 0.016). Vessels with lower RFR had lower QFR-PPG (0.72 vs. 0.82, P = 0.002), hyperemic longitudinal MBF gradient (1.14 vs. 2.22, P = 0.003) and △longitudinal MBF gradient (0.50 vs. 1.02, P = 0.003). QFR-PPG, hyperemic longitudinal MBF gradient and △longitudinal MBF gradient showed comparable diagnostic performances for predicting decreased RFR (area under curve [AUC]: 0.82 vs. 0.81 vs. 0.75, P = NS) or QFR (AUC: 0.83 vs. 0.72 vs. 0.80, P = NS). In addition, QFR-PPG and QFR in combination showed incremental value compared with QFR for predicting RFR (AUC = 0.83 vs. 0.73, P = 0.046, net reclassification index = 0.508, P = 0.001). CONCLUSION: QFR-PPG significantly correlated with longitudinal MBF gradient and △longitudinal MBF gradient when used for physiological coronary diffuseness assessment. All three parameters had high accuracy in predicting RFR or QFR. Adding physiological diffuseness assessment increased accuracy for predicting myocardial ischemia.

Comparison of 2D-QCA, 3D-QCA and coronary angiography derived FFR in predicting myocardial ischemia assessed by CZT-SPECT MPI.

BACKGROUND: Angiography derived fractional flow reserve (angio-FFR) has been proposed. This study aimed to assess its diagnostic performance with cadmium-zinc-telluride single emission computed tomography (CZT-SPECT) as reference. METHODS AND RESULTS: Patients underwent CZT-SPECT within 3 months of coronary angiography were included. Angio-FFR computation was performed using computational fluid dynamics. Percent diameter (%DS) and area stenosis (%AS) were measured by quantitative coronary angiography. Myocardial ischemia was defined as a summed difference score ≥ 2 in a vascular territory. Angio-FFR ≤ 0.80 was considered abnormal. 282 coronary arteries in 131 patients were analyzed. Overall accuracy of angio-FFR to detect ischemia on CZT-SPECT was 90.43%, with a sensitivity of 62.50% and a specificity of 98.62%. The diagnostic performance (= area under ROC = AUC) of angio-FFR [AUC = 0.91, 95% confidence intervals (CI) 0.86-0.95] was similar as those of %DS (AUC = 0.88, 95% CI 0.84-0.93, p = 0.326) and %AS (AUC = 0.88, 95% CI 0.84-0.93 p = 0.241) by 3D-QCA, but significantly higher than those of %DS (AUC = 0.59, 95% CI 0.51-0.67, p < 0.001) and %AS (AUC = 0.59, 95% CI 0.51-0.67, p < 0.001) by 2D-QCA. However, in vessels with 50-70% stenoses, AUC of angio-FFR was significantly higher than those of %DS (0.80 vs. 0.47, p < 0.001) and %AS (0.80 vs. 0.46, p < 0.001) by 3D-QCA and %DS (0.80 vs. 0.66, p = 0.036) and %AS (0.80 vs. 0.66, p = 0.034) by 2D-QCA. CONCLUSION: Angio-FFR had a high accuracy in predicting myocardial ischemia assessed by CZT-SPECT, which is similar as 3D-QCA but significantly higher than 2D-QCA. While in intermediate lesions, angio-FFR is better than 3D-QCA and 2D-QCA in assessing myocardial ischemia.

Pre-stenting angiography-FFR based physiological map provides virtual intervention and predicts physiological and clinical outcomes.

BACKGROUND: Angiography-derived fractional flow reserve (FFR) (angio-FFR) has been validated against FFR and could provide virtual pullback. However, whether a physiological map can be generated by angio-FFR and its clinical value remains unclear. We aimed to investigate the feasibility of physiological map created from angio-FFR pullback and its value in predicting physiological and clinical outcomes after stenting. METHODS: An angio-FFR physiological map was generated by overlaying the virtual pullback onto coronary angiogram, to calculate physiological stenosis severity, length, and intensity (Δangio-FFR/mm). This map in combination with virtual stenting was used to predict the best-case post-percutaneous coronary intervention (PCI) angio-FFR (angio-FFRpredicted ) according to the stented segments, and this was compared with the actual achieved post-PCI angio-FFR (angio-FFRachieved ). Additionally, prognostic value of predicted angio-FFR was investigated. RESULTS: Three hundred twenty-nine vessels with paired analyzable pre- and post-PCI angio-FFR were included. Physiological map was created successfully in all vessels. After successful PCI, angio-FFRpredicted and angio-FFRachieved were significantly correlated (r = 0.82, p < 0.001) with small difference (mean difference: -0.010 ± 0.035). In the virtual PCI only covering the segment with high angio-FFR intensity, the same physiological outcome can be achieved with shorter stent length (14.1 ± 8.9 vs. 34.5 ± 15.8 mm, p < 0.001). Suboptimal angio-FFRpredicted was associated with increased risk of 2-year vessel-oriented composite endpoint (adjusted hazard ratio: 3.71; 95% confidence interval: 1.50-9.17). CONCLUSIONS: Angio-FFR pullback could provide a physiological map of the interrogated coronary vessels by integrating angio-FFR pullback and angiography. Before a PCI, the physiological map can predict the physiological and clinical outcomes after stenting.

Coronary CT angiography-derived plaque characteristics and physiologic patterns for peri-procedural myocardial infarction and subsequent events.

AIMS: Peri-procedural myocardial infarction (PMI) after percutaneous coronary intervention (PCI) has been shown to be associated with worse clinical outcomes. We aimed to investigate the value of coronary plaque characteristics and physiologic disease patterns (focal vs. diffuse) assessed by coronary computed tomography angiography (CTA) in predicting PMI and adverse events. METHODS AND RESULTS: Three hundred fifty-nine patients with normal pre-PCI high-sensitivity cardiac troponin T (hs-cTnT) underwent CTA before PCI were analysed. The high-risk plaque characteristics (HRPC) were assessed on CTA. The physiologic disease pattern was characterized using CTA fractional flow reserve-derived pullback pressure gradients (FFRCT PPG). PMI was defined as an increase in hs-cTnT to >5 times the upper limit of normal after PCI. The major adverse cardiovascular events (MACE) were a composite of cardiac death, spontaneous myocardial infarction, and target vessel revascularization. The presence of ≥3 HRPC in the target lesions [odds ratio (OR) 2.21, 95% confidence interval (CI) 1.29-3.80, P = 0.004] and low FFRCT PPG (OR 1.23, 95% CI 1.02-1.52, P = 0.028) were independent predictors of PMI. In a four-group classification according to HRPC and FFRCT PPG, patients with ≥3 HRPC and low FFRCT PPG had the highest risk of MACE (19.3%; overall P = 0.001). Moreover, the presence of ≥3 HRPC and low FFRCT PPG was an independent predictor of MACE and showed incremental prognostic value compared with a model with clinical risk factors alone [C index = 0.78 vs. 0.60, P = 0.005, net reclassification index = 0.21 (95% CI: 0.04-0.48), P = 0.020]. CONCLUSIONS: Coronary CTA can evaluate plaque characteristics and physiologic disease patterns simultaneously, which plays an important role for risk stratification before PCI.

Prognostic value of combined coronary angiography-derived IMR and myocardial perfusion imaging by CZT SPECT in INOCA.

BACKGROUND: A significant proportion of ischemia with non-obstructive coronary artery disease (INOCA) demonstrate coronary microvascular dysfunction (CMD), a condition associated with abnormal myocardial perfusion imaging (MPI) and adverse outcomes. Coronary angiography-derived index of microvascular resistance (caIMR) is a novel non-invasive technique to assess CMD. We aimed to investigate the prognostic value of combined caIMR and MPI by CZT SPECT in INOCA patients. METHODS: Consecutive 151 patients with chest pain and < 50% coronary stenosis who underwent coronary angiography and MPI within 3 months were enrolled. caIMR was calculated by computational pressure-flow dynamics. CMD was defined as caIMR ≥ 25. The endpoint was major adverse cardiac events (MACE: cardiovascular death, nonfatal myocardial infarction, revascularization, angina-related rehospitalization, heart failure, and stroke). RESULTS: Of all INOCA patients, CMD was present in 93 (61.6%) patients. The prevalence of abnormal MPI was significantly higher in CMD compared with non-CMD patients (40.9% vs 13.8%, P < .001). CMD showed a higher risk of MACE than non-CMD patients. Patients with both CMD and abnormal MPI had the worst prognosis, followed by patients with CMD and normal MPI (log-rank P < .001). Cox regression analysis identified CMD (HR 3.121, 95%CI 1.221-7.974, P = .017) and MPI (HR 2.704, 95%CI 1.030-7.099, P = .043) as predictive of MACE. The prognostic value of INOCA patients enhanced significantly by adding CMD and MPI to the model with clinical risk factors (AUC = 0.777 vs 0.686, P = .030). CONCLUSION: caIMR-derived CMD is associated with increased risk of MACE among INOCA patients. Patients with abnormalities on both caIMR and MPI had the worse outcomes.

Association of Lipoprotein (a) With Coronary-Computed Tomography Angiography-Assessed High-Risk Coronary Disease Attributes and Cardiovascular Outcomes.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular events. This study evaluated the relationship between Lp(a) and high-risk attributes by coronary computed tomography angiography as well as their prognostic value. METHODS: Lp(a) and coronary computed tomography angiography from 377 consecutive patients at Zhongshan Hospital (Shanghai, China) were evaluated. High-risk attributes were defined as high-risk morphological attributes (low attenuation plaque, positive remodeling, napkin-ring sign, spotty calcification, minimum lumen area <4 mm2, or plaque burden [ratio between cross-sectional plaque area at the site of maximum stenosis and cross-sectional vessel area] ≥70%); inflammatory attribute represented by fat attenuation index; high-risk physiological attributes [lesion-specific ischemia defined by fractional flow reserve by coronary computed tomography angiography ≤0.8, physiologic diffuseness defined by fractional flow reserve by coronary computed tomography angiography pullback pressure gradient]. Total plaque volume in mm3 was also quantified. Quintiles or binary classification of Lp(a) levels were used to evaluate its relationships with plaque features and clinical outcomes with ANOVA, Cox models, and log-rank tests, as appropriate. The major adverse cardiovascular event included cardiovascular death, nonfatal myocardial infarction, and target vessel revascularization. RESULTS: Lp(a) was significantly associated with total plaque volume (P=0.004), fat attenuation index (P=0.031), and fractional flow reserve by coronary computed tomography angiography pullback pressure gradient (P=0.038). Patients with a high Lp(a) level had a higher total plaque volume (393.3 mm3 versus 293.9 mm3, P<0.001), lower pullback pressure gradient (0.62 versus 0.69, P=0.023), higher fat attenuation index (-70.5HU versus -73.9HU, P=0.004), and higher incidence of major adverse cardiovascular event (14.5% versus 6.3%, adjusted hazard ratio: 2.52, 95% CI: 1.12-5.63, P=0.025). In a 4-group classification according to Lp(a) and high-risk attributes, patients with high Lp(a) and ≥3 high-risk attributes had the highest risk of major adverse cardiovascular event (25.9%; overall P<0.001). Causal mediation analysis revealed that around 40% of the prognostic effect of Lp(a) was mediated by high-risk attributes. CONCLUSIONS: Lp(a) level is associated with coronary computed tomography angiography high-risk characteristics, including morphologic, physiologic, and inflammatory attributes as well as major adverse cardiovascular event. This effect is partly mediated by inflammation and vulnerable plaque. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05323227.

Prognostic Implications of Quantitative Flow Ratio-Derived Physiological 2-Dimensional Residual Disease Patterns After Stenting.

BACKGROUND: Post-percutaneous coronary intervention (PCI) residual disease is associated with clinical outcomes. Nevertheless, the prognostic value of residual disease patterns remains unknown. OBJECTIVES: This study aimed to evaluate clinical implications of 2-dimensional residual disease patterns after PCI. METHODS: One thousand six hundred seven vessels that underwent successful PCI were included. Two-dimensional residual disease patterns were determined by visual assessment or the quantitative flow ratio (QFR)-derived pull back pressure gradient index (with a cutoff value of 0.78 to define predominant focal versus diffuse disease) and instantaneous QFR gradient per unit length (with a cutoff value of ≥0.005/mm to define a major gradient). The clinical outcome was the 2-year vessel-oriented composite outcome (VOCO). RESULTS: Residual disease patterns were classified into 4 groups: predominant focal without and with a major gradient (group 1 [n = 1,058] and group 2 [n = 63], respectively) and predominant diffuse without and with a major gradient (group 3 [n = 318] and group 4 [n = 168], respectively). At 2 years, VOCO was lowest in group 1 (1.4% vs 5.4% in group 2 vs 4.8% in group 3 vs 8.5% in group 4, all P < 0.05), whereas there was no prognostic value for classifications by visual assessment. Physiological residual disease patterns were independently associated with VOCO and showed increased prognostic value when introduced to a model with clinical risk factors only (C index: 0.77 vs. 0.68, P = 0.008; net reclassification improvement: 0.65, P < 0.001; integrated discrimination improvement: 0.020, P < 0.001). CONCLUSIONS: Objective analysis of post-PCI QFR pull backs using the concept of 2-dimensional residual disease patterns is feasible and superior to visual assessments. The residual disease patterns were independently associated with VOCO at 2 years.

A Deep Learning-based Method to Extract Lumen and Media-Adventitia in Intravascular Ultrasound Images.

Intravascular ultrasound (IVUS) imaging allows direct visualization of the coronary vessel wall and is suitable for assessing atherosclerosis and the degree of stenosis. Accurate segmentation and lumen and median-adventitia (MA) measurements from IVUS are essential for such a successful clinical evaluation. However, current automated segmentation by commercial software relies on manual corrections, which is time-consuming and user-dependent. We aim to develop a deep learning-based method using an encoder-decoder deep architecture to automatically and accurately extract both lumen and MA border. Inspired by the dual-path design of the state-of-the-art model IVUS-Net, our method named IVUS-U-Net++ achieved an extension of the U-Net++ model. More specifically, a feature pyramid network was added to the U-Net++ model, enabling the utilization of feature maps at different scales. Following the segmentation, the Pearson correlation and Bland-Altman analyses were performed to evaluate the correlations of 12 clinical parameters measured from our segmentation results and the ground truth. A dataset with 1746 IVUS images from 18 patients was used for training and testing. Our segmentation model at the patient level achieved a Jaccard measure (JM) of 0.9080 ± 0.0321 and a Hausdorff distance (HD) of 0.1484 ± 0.1584 mm for the lumen border; it achieved a JM of 0.9199 ± 0.0370 and an HD of 0.1781 ± 0.1906 mm for the MA border. The 12 clinical parameters measured from our segmentation results agreed well with those from the ground truth (all p-values are smaller than .01). Our proposed method shows great promise for its clinical use in IVUS segmentation.

Anatomic and Hemodynamic Plaque Characteristics for Subsequent Coronary Events.

Objectives: While coronary computed tomography angiography (CCTA) enables the evaluation of anatomic and hemodynamic plaque characteristics of coronary artery disease (CAD), the clinical roles of these characteristics are not clear. We sought to evaluate the prognostic implications of CCTA-derived anatomic and hemodynamic plaque characteristics in the prediction of subsequent coronary events. Methods: The study cohort consisted of 158 patients who underwent CCTA with suspected CAD within 6-36 months before percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) or unstable angina and age-/sex-matched 62 patients without PCI as the control group. Preexisting high-risk plaque characteristics (HRPCs: low attenuation plaque, positive remodeling, napkin-ring sign, spotty calcification, minimal luminal area <4 mm2, or plaque burden ≥70%) and hemodynamic parameters (per-vessel fractional flow reserve [FFRCT], per-lesion ΔFFRCT, and percent ischemic myocardial mass) were analyzed from prior CCTA. The primary outcome was a subsequent coronary event, which was defined as a composite of vessel-specific MI or revascularization for unstable angina. The prognostic impact of clinical risk factors, HRPCs, and hemodynamic parameters were compared between vessels with (160 vessels) and without subsequent coronary events (329 vessels). Results: Vessels with a subsequent coronary event had higher number of HRPCs (2.6 ± 1.4 vs. 2.3 ± 1.4, P = 0.012), lower FFRCT (0.76 ± 0.13 vs. 0.82 ± 0.11, P < 0.001), higher ΔFFRCT (0.14 ± 0.12 vs. 0.09 ± 0.08, P < 0.001), and higher percent ischemic myocardial mass (29.0 ± 18.5 vs. 26.0 ± 18.4, P = 0.022) than those without a subsequent coronary event. Compared with clinical risk factors, HRPCs and hemodynamic parameters showed higher discriminant abilities for subsequent coronary events with ΔFFRCT being the most powerful predictor. HRPCs showed additive discriminant ability to clinical risk factors (c-index 0.620 vs. 0.558, P = 0.027), and hemodynamic parameters further increased discriminant ability (c-index 0.698 vs. 0.620, P = 0.001) and reclassification abilities (NRI 0.460, IDI 0.061, P < 0.001 for all) for subsequent coronary events. Among vessels with negative FFRCT (>0.80), adding HRPCs into clinical risk factors significantly increased discriminant and reclassification abilities for subsequent coronary events (c-index 0.687 vs. 0.576, P = 0.005; NRI 0.412, P = 0.002; IDI 0.064, P = 0.001) but not for vessels with positive FFRCT (≤0.80). Conclusion: In predicting subsequent coronary events, both HRPCs and hemodynamic parameters by CCTA allow better prediction of subsequent coronary events than clinical risk factors. HRPCs provide more incremental predictability than clinical risk factors alone among vessels with negative FFRCT but not among vessels with positive FFRCT. Clinical Trial Registration: PreDiction and Validation of Clinical CoursE of Coronary Artery DiSease With CT-Derived Non-INvasive HemodYnamic Phenotyping and Plaque Characterization (DESTINY Study), NCT04794868.

Prognostic Implications of Prestent Pullback Pressure Gradient and Poststent Quantitative Flow Ratio in Patients Undergoing Percutaneous Coronary Intervention.

Background Coronary diffuse disease associates with poor outcomes, but little is known about its role after percutaneous coronary intervention (PCI). We aimed to investigate the prognostic implication of pre-PCI focal or diffuse disease patterns combined with post-PCI quantitative flow ratio (QFR). Methods and Results Pre-PCI QFR derived pullback pressure gradient (PPG) (QFR-PPG) was measured to assess physiological disease patterns for 1685 included vessels; the vessels were classified according to dichotomous pre-PCI QFR-PPG and post-PCI QFR. Vessel-oriented composite outcome, a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death at 2 years was compared among these groups. Vessels with low pre-PCI PPG (3.9% versus 2.0%, hazard ratio [HR], 1.93; 95% CI, 1.08-3.44; P=0.02) or low post-PCI QFR (9.8% versus 2.7%, HR, 3.78; 95% CI, 1.61-8.87; P=0.001) demonstrated higher vessel-oriented composite outcome risk after stent implantation. Of note, despite high post-PCI QFR achieved, vessels with low pre-PCI QFR-PPG presented higher risk of vessel-oriented composite outcome than those with high pre-PCI QFR-PPG (3.7% versus 1.8%, HR, 2.03; 95% CI, 1.09-3.76; P=0.03) and pre-PCI QFR-PPG demonstrated direct prognostic effect not mediated by post-PCI QFR. Integration of groups classified by pre-PCI QFR-PPG and post-PCI QFR showed significantly higher discriminant and reclassification abilities than clinical factors (C-index 0.77 versus 0.72, P=0.03; integrated discrimination improvement 0.93%, P=0.04; net reclassification index 0.33, P=0.02). Conclusions Prognostic value of pre-PCI focal or diffuse disease patterns assessed by QFR-PPG index was retained even after successful PCI, which is mostly explained by its direct effect that was not mediated by post-PCI QFR. Integration of both pre-PCI and post-PCI physiological information can provide better risk stratification in vessels with stent implantation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT05104580.