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.

Biodegradable Polymer Versus Polymer-Free Ultrathin Sirolimus-Eluting Stents: Analysis of the Stent Arm Registry From the HOST-IDEA Randomized Trial.

BACKGROUND: The efficacy and safety of each third-generation drug-eluting stent with ultrathin struts and advanced polymer technology remain unclear. We investigated the clinical outcomes of percutaneous coronary intervention using the Coroflex ISAR polymer-free sirolimus-eluting stent (SES) or Orsiro biodegradable polymer SES. METHODS: The HOST-IDEA trial (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Coronary Intervention With Next-Generation Drug-Eluting Stent Platforms and Abbreviated Dual Antiplatelet Therapy), initially designed with a 2×2 factorial approach, sought to randomize patients undergoing percutaneous coronary intervention based on dual antiplatelet therapy duration (3 versus 12 months) and stent type (Coroflex ISAR versus Orsiro). Despite randomizing 2013 patients for dual antiplatelet therapy duration, the stent arm transitioned to a registry format during the trial. Among these, 328 individuals (16.3%) were randomized for Coroflex ISAR or Orsiro SES, while 1685 (83.7%) underwent percutaneous coronary intervention without stent-type randomization. In this study, the Coroflex ISAR (n=559) and Orsiro groups (n=1449) were matched using a propensity score. The prespecified primary end point was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularization at 12 months. RESULTS: The baseline patient and procedural characteristics were well balanced between the Coroflex ISAR and Orsiro groups after propensity score matching (n=559, each group). The Coroflex ISAR group was significantly associated with a higher rate of target lesion failure, mainly driven by clinically driven target lesion revascularization, compared with the Orsiro group (3.4% versus 1.1%; hazard ratio, 3.21 [95% CI, 1.28-8.05]; P=0.01). A higher risk of target lesion failure in the Coroflex ISAR group was consistently observed across various subgroups. The rates of any bleeding (hazard ratio, 0.85 [95% CI, 0.51-1.40]; P=0.52) and major bleeding (hazard ratio, 1.58 [95% CI, 0.61-4.08]; P=0.34) were comparable between the 2 groups. CONCLUSIONS: In this propensity score-matched analysis of the stent arm registry from the HOST-IDEA trial, the Orsiro SES was associated with significantly better outcomes in terms of 1-year target lesion failure, mainly driven by clinically driven target lesion revascularization, than the Coroflex ISAR SES. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02601157.

Artificial Intelligence-Enabled Quantitative Coronary Plaque and Hemodynamic Analysis for Predicting Acute Coronary Syndrome.

BACKGROUND: A lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization. OBJECTIVES: This study sought to investigate the additive value of artificial intelligence-enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA). METHODS: Among ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort. RESULTS: Among 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA. CONCLUSIONS: AI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328).

Long-term prognostic implications of CT angiography-derived fractional flow reserve: Results from the DISCOVER-FLOW study.

BACKGROUND & OBJECTIVES: The long-term prognostic implications of CT angiography-derived fractional flow reserve (FFRCT) remains unclear. We aimed to explore the long-term outcomes of FFRCT in the first-in-human study of it. MATERIALS & METHODS: A total of 156 vessels from 102 patients with stable coronary artery disease, who underwent coronary CT angiography (CCTA) and invasive FFR measurement, were followed. The primary endpoint was target vessel failure (TVF), including cardiovascular death, target vessel myocardial infarction, and target vessel revascularization. Outcome analysis with FFRCT was performed on a per-vessel basis using a marginal Cox proportional hazard model. RESULTS: During median 9.9 years of follow-up, TVF occurred in 20 (12.8%) vessels. FFRCT â€‹≤0.80 discriminated TVF (hazard ratio [HR] 2.61, 95% confidence interval [CI] 1.06, 6.45). Among 94 vessels with deferral of percutaneous coronary intervention (PCI), TVF risk was inversely correlated with FFRCT â€‹(HR 0.62 per 0.1 increase, 95% CI 0.44, 0.86), with the cumulative incidence of TVF being 2.6%, 15.2%, and 28.6% for vessels with FFRCT â€‹>0.90, 0.81-0.90, and ≤0.80, respectively (p-for-trend 0.005). Predictive value for clinical outcomes of FFRCT was similar to that of invasive FFR (c-index 0.79 vs 0.71, P â€‹= â€‹0.28). The estimated TVF risk was higher in the deferral of PCI group than the PCI group for vessels with FFRCT ≤0.81. CONCLUSION: FFRCT showed improved long-term risk stratification and displayed a risk continuum similar to invasive FFR. CLINICAL TRIAL REGISTRATION: NCT01189331.

Relationship of Coronary Angiography-Derived Radial Wall Strain With Functional Significance, Plaque Morphology, and Clinical Outcomes.

BACKGROUND: Coronary angiography-derived radial wall strain (RWS) is a newly developed index that can be readily accessed and describes the biomechanical features of a lesion. OBJECTIVES: The authors sought to investigate the association of RWS with fractional flow reserve (FFR) and high-risk plaque (HRP), and their relative prognostic implications. METHODS: We included 484 vessels (351 patients) deferred after FFR measurement with available RWS data and coronary computed tomography angiography. On coronary computed tomography angiography, HRP was defined as a lesion with both minimum lumen area <4 mm2 and plaque burden ≥70%. The primary outcome was target vessel failure (TVF), a composite of target vessel revascularization, target vessel myocardial infarction, or cardiac death. RESULTS: The mean FFR and RWSmax were 0.89 ± 0.07 and 11.2% ± 2.5%, respectively, whereas 27.7% of lesions had HRP, 15.1% had FFR ≤0.80. An increase in RWSmax was associated with a higher risk of FFR ≤0.80 and HRP, which was consistent after adjustment for clinical or angiographic characteristics (all P < 0.05). An increment of RWSmax was related to a higher risk of TVF (HR: 1.23 [95% CI: 1.03-1.47]; P = 0.022) with an optimal cutoff of 14.25%. RWSmax >14% was a predictor of TVF after adjustment for FFR or HRP components (all P < 0.05) and showed a direct prognostic effect on TVF, not mediated by FFR ≤0.80 or HRP in the mediation analysis. When high RWSmax was added to FFR ≤0.80 or HRP, there were increasing outcome trends (all P for trend <0.001). CONCLUSIONS: RWS was associated with coronary physiology and plaque morphology but showed independent prognostic significance.

Physiology- or Imaging-Guided Strategies for Intermediate Coronary Stenosis.

Importance: Treatment strategies for intermediate coronary lesions guided by fractional flow reserve (FFR) and intravascular ultrasonography (IVUS) have shown comparable outcomes. Identifying low-risk deferred vessels to ensure the safe deferral of percutaneous coronary intervention (PCI) and high-risk revascularized vessels that necessitate thorough follow-up can help determine optimal treatment strategies. Objectives: To investigate outcomes according to treatment types and FFR and IVUS parameters after FFR- or IVUS-guided treatment. Design, Setting, and Participants: This cohort study included patients with intermediate coronary stenosis from the Fractional Flow Reserve and Intravascular Ultrasound-Guided Intervention Strategy for Clinical Outcomes in Patients With Intermediate Stenosis (FLAVOUR) trial, an investigator-initiated, prospective, open-label, multicenter randomized clinical trial that assigned patients into an IVUS-guided strategy (which recommended PCI for minimum lumen area [MLA] ≤3 mm2 or 3 mm2 to 4 mm2 with plaque burden [PB] ≥70%) or an FFR-guided strategy (which recommended PCI for FFR ≤0.80). Data were analyzed from November to December 2022. Exposures: FFR or IVUS parameters within the deferred and revascularized vessels. Main Outcomes and Measures: The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, and revascularization at 2 years. Results: A total of 1619 patients (mean [SD] age, 65.1 [9.6] years; 1137 [70.2%] male) with 1753 vessels were included in analysis. In 950 vessels for which revascularization was deferred, incidence of TVF was comparable between IVUS and FFR groups (3.8% vs 4.1%; P = .72). Vessels with FFR greater than 0.92 in the FFR group and MLA greater than 4.5 mm2 or PB of 58% or less in the IVUS group were identified as low-risk deferred vessels, with a decreased risk of TVF (hazard ratio [HR], 0.25 [95% CI, 0.09-0.71]; P = .009). In 803 revascularized vessels, the incidence of TVF was comparable between IVUS and FFR groups (3.6% vs 3.7%; P = .95), which was similar in the revascularized vessels undergoing PCI optimization (4.2% vs 2.5%; P = .31). Vessels with post-PCI FFR of 0.80 or less in the FFR group or minimum stent area of 6.0 mm2 or less or with PB at stent edge greater than 58% in the IVUS group had an increased risk for TVF (HR, 7.20 [95% CI, 3.20-16.21]; P < .001). Conclusions and Relevance: In this cohort study of patients with intermediate coronary stenosis, FFR- and IVUS-guided strategies showed comparable outcomes in both deferred and revascularized vessels. Binary FFR and IVUS parameters could further define low-risk deferred vessels and high-risk revascularized vessels.

Practical Application of Coronary Physiologic Assessment: Asia-Pacific Expert Consensus Document: Part 2.

Coronary physiologic assessment is performed to measure coronary pressure, flow, and resistance or their surrogates to enable the selection of appropriate management strategy and its optimization for patients with coronary artery disease. The value of physiologic assessment is supported by a large body of clinical data that has led to major recommendations in all practice guidelines. This expert consensus document aims to convey practical and balanced recommendations and future perspectives for coronary physiologic assessment for physicians and patients in the Asia-Pacific region, based on updated information in the field that includes both wire- and image-based physiologic assessment. This is Part 2 of the whole consensus document, which provides theoretical and practical information on physiologic indexes for specific clinical conditions and patient statuses.

Prognostic Implications of Individual and Combinations of Resting and Hyperemic Coronary Pressure and Flow Parameters.

Background: Coronary pressure- and flow-derived parameters have prognostic value. Objectives: This study aims to investigate the individual and combined prognostic relevance of pressure and flow parameters reflecting resting and hyperemic conditions. Methods: A total of 1,971 vessels deferred from revascularization after invasive pressure and flow assessment were included from the international multicenter registry. Abnormal resting pressure and flow were defined as distal coronary pressure/aortic pressure ≤0.92 and high resting flow (1/resting mean transit time >2.4 or resting average peak flow >22.7 cm/s), and abnormal hyperemic pressure and flow as fractional flow reserve ≤0.80 and low hyperemic flow (1/hyperemic mean transit time <2.2 or hyperemic average peak flow <25.0 cm/s), respectively. The clinical endpoint was target vessel failure (TVF), myocardial infarction (MI), or cardiac death at 5 years. Results: The mean % diameter stenosis was 46.8% ± 16.5%. Abnormal pressure and flow were independent predictors of TVF and cardiac death/MI (all P < 0.05). The risk of 5-year TVF or MI/cardiac death increased proportionally with neither, either, and both abnormal resting pressure and flow, and abnormal hyperemic pressure and flow (all P for trend < 0.001). Abnormal resting pressure and flow were associated with a higher rate of TVF or MI/cardiac death in vessels with normal fractional flow reserve; this association was similar for abnormal hyperemic pressure and flow in vessels with normal resting distal coronary pressure/aortic pressure (all P < 0.05). Conclusions: Abnormal resting and hyperemic pressure and flow were independent prognostic predictors. The abnormal flow had an additive prognostic value for pressure in both resting and hyperemic conditions with complementary prognostic between resting and hyperemic parameters.

Machine-learning-based prediction of fractional flow reserve after percutaneous coronary intervention.

BACKGROUND AND AIMS: Post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) reflects residual atherosclerotic burden and is associated with future events. How much post-PCI FFR can be predicted based on baseline basic information and the clinical relevance have not been investigated. METHODS: We compiled a multicenter registry of patients undergoing pre- and post-PCI FFR. Machine-learning (ML) algorithms were designed to predict post-PCI FFR levels from baseline demographics, quantitative coronary angiography, and pre-PCI FFR. FFR deviation was defined as actual minus ML-predicted post-PCI FFR levels, and its association with incident target vessel failure (TVF) was evaluated. RESULTS: Median (IQR) pre- and post-PCI FFR values were 0.71 (0.61, 0.77) and 0.88 (0.84, 0.93), respectively. The Spearman correlation coefficient of the actual and predicted post-PCI FFR was 0.54 (95% CI: 0.52, 0.57). FFR deviation was non-linearly associated with incident TVF (HR [95% CI] with Q3 as reference: 1.65 [1.14, 2.39] in Q1, 1.42 [0.98, 2.08] in Q2, 0.81 [0.53, 1.26] in Q4, and 1.04 [0.69, 1.56] in Q5). A model with polynomial function of continuous FFR deviation indicated increasing TVF risk for FFR deviation ≤0 but plateau risk with FFR deviation >0. CONCLUSIONS: An ML-based algorithm using baseline data moderately predicted post-PCI FFR. The deviation of post-PCI FFR from the predicted value was associated with higher vessel-oriented event.

Comparison of Antiplatelet Monotherapies After Percutaneous Coronary Intervention According to Clinical, Ischemic, and Bleeding Risks.

BACKGROUND: Clopidogrel was superior to aspirin monotherapy in secondary prevention after percutaneous coronary intervention (PCI). OBJECTIVES: The purpose of this study was to evaluate the benefits of clopidogrel across high-risk subgroups METHODS: This was a post hoc analysis of the HOST-EXAM (Harmonizing Optimal Strategy for Treatment of coronary artery diseases-EXtended Antiplatelet Monotherapy) trial that randomly assigned patients who were event free for 6 to 18 months post-PCI on dual antiplatelet therapy (DAPT) to clopidogrel or aspirin monotherapy. Two clinical risk scores were used for risk stratification: the DAPT score and the Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention (TRS 2°P) (the sum of age ≥75 years, diabetes, hypertension, current smoking, peripheral artery disease, stroke, coronary artery bypass grafting, heart failure, and renal dysfunction). The primary composite endpoint was a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission because of acute coronary syndrome, and major bleeding (Bleeding Academic Research Consortium type ≥3) at 2 years after randomization. RESULTS: Among 5,403 patients, clopidogrel monotherapy showed a lower rate of the primary composite endpoint than aspirin monotherapy (HR: 0.73; 95% CI: 0.59-0.90). The benefit of clopidogrel over aspirin was consistent regardless of TRS 2°P (high TRS 2°P [≥3] group: HR: 0.65 [95% CI: 0.44-0.96]; and low TRS 2°P [<3] group: HR: 0.77 [95% CI: 0.60-0.99]) (P for interaction = 0.454) and regardless of DAPT score (high DAPT score [≥2] group: HR: 0.68 [95% CI: 0.46-1.00]; and low DAPT score [<2] group: HR: 0.75 [95% CI: 0.59-0.96]) (P for interaction = 0.662). The association was similar for the individual outcomes. CONCLUSIONS: The beneficial effect of clopidogrel over aspirin monotherapy was consistent regardless of clinical risk or relative ischemic and bleeding risks compared with aspirin monotherapy. (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis- EXtended Antiplatelet Monotherapy [HOST-EXAM]; NCT02044250).

Coronary Physiology-Based Approaches for Plaque Vulnerability: Implications for Risk Prediction and Treatment Strategies.

In the catheterization laboratory, the measurement of physiological indexes can help identify functionally significant lesions and has become one of the standard methods to guide treatment decision-making. Plaque vulnerability refers to a coronary plaque susceptible to rupture, enabling risk prediction before coronary events, and it can be detected by defining a certain type of plaque morphology on coronary imaging modalities. Although coronary physiology and plaque vulnerability have been considered different attributes of coronary artery disease, the underlying pathophysiological basis and clinical data indicate a strong correlation between coronary hemodynamic properties and vulnerable plaque. In prediction of coronary events, emerging data have suggested independent and additional implications of a physiology-based approach to a plaque-based approach. This review covers the fundamental interplay between coronary physiology and plaque morphology during disease progression with clinical data supporting this relationship and examines the clinical relevance of physiological indexes in prediction of clinical outcomes and therapeutic decision-making along with plaque vulnerability.

Clinical and Vessel Characteristics Associated With Hard Outcomes After PCI and Their Combined Prognostic Implications.

Background Cardiac death or myocardial infarction still occurs in patients undergoing contemporary percutaneous coronary intervention (PCI). We aimed to identify adverse clinical and vessel characteristics related to hard outcomes after PCI and to investigate their individual and combined prognostic implications. Methods and Results From an individual patient data meta-analysis of 17 cohorts of patients who underwent post-PCI fractional flow reserve measurement after drug-eluting stent implantation, 2081 patients with available clinical and vessel characteristics were analyzed. The primary outcome was cardiac death or target-vessel myocardial infarction at 2 years. The mean age of patients was 64.2±10.2 years, and the mean angiographic percent diameter stenosis was 63.9%±14.3%. Among 11 clinical and 8 vessel features, 4 adverse clinical characteristics (age ≥65 years, diabetes, chronic kidney disease, and left ventricular ejection fraction <50%) and 2 adverse vessel characteristics (post-PCI fractional flow reserve ≤0.80 and total stent length ≥54 mm) were identified to independently predict the primary outcome (all P<0.05). The number of adverse vessel characteristics had additive predictability for the primary end point to that of adverse clinical characteristics (area under the curve 0.72 versus 0.78; P=0.03) and vice versa (area under the curve 0.68 versus 0.78; P=0.03). The cumulative event rate increased in the order of none, either, and both of adverse clinical characteristics ≥2 and adverse vessel characteristics ≥1 (0.3%, 2.4%, and 5.3%; P for trend <0.01). Conclusions In patients undergoing drug-eluting stent implantation, adverse clinical and vessel characteristics were associated with the risk of cardiac death or target-vessel myocardial infarction. Because these characteristics showed independent and additive prognostic value, their integrative assessment can optimize post-PCI risk stratification. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04684043. www.crd.york.ac.uk/prospero/. Unique Identifier: CRD42021234748.

Sex Differences in Fractional Flow Reserve- or Intravascular Ultrasound-Guided Percutaneous Coronary Intervention.

BACKGROUND: A recent randomized trial reported fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) strategy was noninferior to the intracoronary ultrasound (IVUS)-guided PCI strategy with respect to clinical outcomes with fewer revascularizations. OBJECTIVES: This study sought to investigate the sex differences in treatment and clinical outcomes according to physiology- or imaging-guided PCI strategies. METHODS: In this secondary analysis of the FLAVOUR (Fractional Flow Reserve or Intravascular Ultrasonography to Guide PCI) trial, the impact of sex on procedural characteristics, PCI rate, and outcomes according to different strategies and treatment types (PCI vs deferral of PCI) was analyzed. The primary outcome was target vessel failure (TVF) at 24 months, defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization. RESULTS: Of 1,619 patients, 30% were women. Compared with men, women had a smaller minimal lumen area, smaller plaque burden, and higher FFR. They had a lower PCI rate (40.8% vs 47.9%; P = 0.008), which was mainly contributed by FFR guidance. Overall, women showed a lower TVF rate (2.4% vs 4.5%). According to the treatment type, the cumulative incidence of TVF was lower in women than in men among those with the deferral of PCI (1.7% vs 5.2%). However, this trend was not observed in patients who underwent PCI. In both women and men, there were no differences in clinical outcomes between the FFR- and IVUS-guided strategies. CONCLUSIONS: In cases of intermediate stenosis, despite receiving fewer interventions, women had more favorable outcomes than men. The use of FFR led to a lower PCI rate but had a similar prognostic value compared with IVUS in both women and men.

Data-driven mortality risk prediction of severe degenerative mitral regurgitation patients undergoing mitral valve surgery.

AIMS: The outcomes of mitral valve replacement/repair (MVR) in severe degenerative mitral regurgitation (MR) patients depend on various risk factors. We aimed to develop a risk prediction model for post-MVR mortality in severe degenerative MR patients using machine learning. METHODS AND RESULTS: Consecutive severe degenerative MR patients undergoing MVR were analysed (n = 1521; 70% training/30% test sets). A random survival forest (RSF) model was constructed, with 3-year post-MVR all-cause mortality as the outcome. Partial dependency plots were used to define the thresholds of each risk factor. A simple scoring system (MVR-score) was developed to stratify post-MVR mortality risk. At 3 years following MVR, 90 patients (5.9%) died in the entire cohort (59 and 31 deaths in the training and test sets). The most important predictors of mortality in order of importance were age, haemoglobin, valve replacement, glomerular filtration rate, left atrial dimension, and left ventricular (LV) end-systolic diameter. The final RSF model with these six variables demonstrated high predictive performance in the test set (3-year C-index 0.880, 95% confidence interval 0.834-0.925), with mortality risk increased strongly with left atrial dimension >55 mm, and LV end-systolic diameter >45 mm. MVR-score demonstrated effective risk stratification and had significantly higher predictability compared to the modified Mitral Regurgitation International Database score (3-year C-index 0.803 vs. 0.750, P = 0.034). CONCLUSION: A data-driven machine learning model provided accurate post-MVR mortality prediction in severe degenerative MR patients. The outcome following MVR in severe degenerative MR patients is governed by both clinical and echocardiographic factors.

Long-term prognostic implications of hemodynamic and plaque assessment using coronary CT angiography.

BACKGROUND AND AIMS: Hemodynamic and plaque characteristics can be analyzed using coronary CT angiography (CTA). We aimed to explore long-term prognostic implications of hemodynamic and plaque characteristics using coronary CT angiography (CTA). METHODS: Invasive fractional flow reserve (FFR) and CTA-derived FFR (FFRCT) were undertaken for 136 lesions in 78 vessels and followed-up to 10 years until December 2020. FFRCT, wall shear stress (WSS), change in FFRCT across the lesion (ΔFFRCT), total plaque volume (TPV), percent atheroma volume (PAV), and low-attenuation plaque volume (LAPV) for target lesions [L] and vessels [V] were obtained by independent core laboratories. Their collective influence was evaluated for the clinical endpoints of target vessel failure (TVF) and target lesion failure (TLF). RESULTS: During a median follow-up of 10.1 years, PAV[V] (per 10% increase, HR 2.32 [95% CI 1.11-4.86], p = 0.025), and FFRCT[V] (per 0.1 increase, HR 0.56 [95% CI 0.37-0.84], p = 0.006) were independent predictors of TVF for the per-vessel analysis, and WSS[L] (per 100 dyne/cm2 increase, HR 1.43 [1.09-1.88], p = 0.010), LAPV[L] (per 10 mm3 increase, HR 3.81 [1.16-12.5], p = 0.028), and ΔFFRCT[L] (per 0.1 increase, HR 1.39 [1.02-1.90], p = 0.040) were independent predictors of TLF for the per-lesion analysis after adjustment for clinical and lesion characteristics. The addition of both plaque and hemodynamic predictors improved the predictability for 10-year TVF and TLF of clinical and lesion characteristics (all p < 0.05). CONCLUSIONS: Vessel- and lesion-level hemodynamic characteristics, and vessel-level plaque quantity, and lesion-level plaque compositional characteristics assessed by CTA offer independent and additive long-term prognostic value.

Comparison of 3- to 6-Month Versus 12-Month Dual Antiplatelet Therapy After Coronary Intervention Using the Contemporary Drug-Eluting Stents With Ultrathin Struts: The HOST-IDEA Randomized Clinical Trial.

BACKGROUND: Limited data are available on short-term dual antiplatelet therapy (DAPT) after percutaneous coronary intervention using third-generation drug-eluting stents with ultrathin struts and advanced polymer technology. We investigated whether 3- to 6-month DAPT was noninferior to 12-month DAPT after implantation of drug-eluting stents with ultrathin struts and advanced polymer technology. METHODS: We performed an open-label, randomized trial at 37 centers in South Korea. We enrolled patients undergoing percutaneous coronary intervention using the Orsiro biodegradable-polymer sirolimus-eluting stents or the Coroflex ISAR polymer-free sirolimus-eluting stents. Patients with ST-segment-elevation myocardial infarction were excluded. Patients were randomly assigned to receive either 3- to 6-month or 12-month DAPT after percutaneous coronary intervention. The choice of antiplatelet medications was at the physician's discretion. The primary outcome was a net adverse clinical event, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, or major bleeding, defined as Bleeding Academic Research Consortium type 3 or 5 at 12 months. The major secondary outcomes were target lesion failure, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and major bleeding. RESULTS: A total of 2013 patients (mean age, 65.7±10.5 years; 1487 males [73.9%]; 1110 [55.1%] presented with acute coronary syndrome) were randomly assigned to 3- to 6-month DAPT (n=1002) or 12-month DAPT (n=1011). The primary outcome occurred in 37 (3.7%) patients in the 3- to 6-month DAPT group and 41 (4.1%) in the 12-month DAPT group. The noninferiority of the 3- to 6-month DAPT group to the 12-month DAPT group was met (absolute risk difference, -0.4% [1-sided 95% CI, -∞% to 1.1%]; P<0.001 for noninferiority). There were no significant differences in target lesion failure (hazard ratio, 0.98 [95% CI, 0.56-1.71], P=0.94) or major bleeding (hazard ratio, 0.82 [95% CI, 0.41-1.61], P=0.56) between the 2 groups. Across various subgroups, the treatment effect of 3- to 6-month DAPT was consistent for net adverse clinical event. CONCLUSIONS: Among patients undergoing percutaneous coronary intervention using third-generation drug-eluting stents, 3- to 6-month DAPT was noninferior to 12-month DAPT for net adverse clinical event. Further research is needed to generalize this finding to other populations and to determine the ideal regimen for 3- to 6-month DAPT. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02601157.

Atrial Functional Tricuspid Regurgitation: Importance of Atrial Fibrillation and Right Atrial Remodeling and Prognostic Significance.

BACKGROUND: Little is known about the determinants and outcomes of significant atrial functional tricuspid regurgitation (AFTR). OBJECTIVES: The authors aimed to identify risk factors for significant TR in relation to atrial fibrillation-flutter (AF-AFL) and assess its prognostic implications. METHODS: The authors retrospectively studied patients with mild TR with follow-up echocardiography examinations. Significant TR was defined as greater than or equal to moderate TR. AFTR was defined as TR, attributed to right atrial (RA) remodeling or isolated tricuspid annular dilatation, without other primary or secondary etiology, except for AF-AFL. The Mantel-Byar test was used to compare clinical outcomes by progression of AFTR. RESULTS: Of 833 patients with mild TR, 291 (34.9%) had AF-AFL. During the median 4.6 years, significant TR developed in 35 patients, including 33 AFTRs. Significant AFTR occurred in patients with AF-AFL more predominantly than in those patients without AF-AFL (10.3% vs 0.6%; P < 0.001). In Cox analysis, AF-AFL was a strong risk factor for AFTR (adjusted HR: 8.33 [95% CI: 2.34-29.69]; P = 0.001). Among patients with AF-AFL, those who developed significant AFTR had larger baseline RA areas (23.8 vs 19.4 cm2; P < 0.001) and RA area-to-right ventricle end-systolic area ratio (3.0 vs 2.3; P < 0.001) than those who did not. These parameters were independent predictors of AFTR progression. The 10-year major adverse cardiovascular event was significantly higher after progression of AFTR than before or without progression (79.8% vs 8.6%; Mantel-Byar P < 0.001). CONCLUSIONS: In patients with mild TR, significant AFTR developed predominantly in patients with AF-AFL, conferring poor prognosis. RA enlargement, especially with increased RA area-to-right ventricle end-systolic area ratio, was a strong risk factor for progression of AFTR.

Outcomes of non-ischaemic coronary lesions with high-risk plaque characteristics on coronary CT angiography.

BACKGROUND: The integrative implications of quantitative and qualitative plaque characteristics on clinical outcomes and therapeutic guidance have not been fully investigated. AIMS: We aimed to investigate the combined prognostic value of quantitative and qualitative plaque measures and their interactions with treatment modalities and physiological lesion severity. METHODS: Among 697 vessels from 458 patients who underwent fractional flow reserve (FFR)-guided treatment, quantitative high-risk plaque (qn-HRP; plaque burden ≥70% and minimum lumen area <3.3 mm2) and qualitative HRP (ql-HRP; low-attenuation plaque or positive remodelling) were defined on coronary computed tomography angiography (CCTA). The primary endpoint was the vessel-oriented composite outcome (VOCO; a composite of cardiac death, myocardial infarction, or revascularisation). RESULTS: The mean baseline FFR was 0.85±0.12, and 25.8% underwent percutaneous coronary intervention (PCI) during the index procedure. In medically treated lesions, both qn-HRP and ql-HRP were associated with an increased risk of VOCO (p<0.05). Relative to the lesions with qn-HRP(-)/ql-HRP(-),those with qn-HRP(+)/ql-HRP(+) showed a higher risk of VOCO (hazard ratio [HR] 8.36, 95% confidence interval [CI]: 2.86-24.44). The PCI group showed a lower risk for VOCO than the medical treatment group (HR 0.31, 95% CI: 0.11-0.91) in lesions with qn-HRP(+)/ql-HRP(+). This difference was consistent in lesions with an FFR of 0.81-0.90 (HR 0.19, 95 CI: 0.04-0.90), but not in those with an FFR of>0.90. CONCLUSIONS: In non-ischaemic lesions, ql-HRP and qn-HRP showed a synergistic impact on risk assessment and had prognostic interactions with FFR and treatment modalities. Therefore, they need to be integrated into risk stratification and the optimisation of a treatment strategy. CLINICALTRIALS: gov: NCT04037163.

Long-term outcomes in distinct phenogroups of patients with primary mitral regurgitation undergoing valve surgery.

OBJECTIVES: Patients with mitral regurgitation (MR) may be heterogeneous with different risk profiles. We aimed to identify distinct phenogroups of patients with severe primary MR and investigate their long-term prognosis after mitral valve (MV) surgery. METHODS: The retrospective cohort of patients with severe primary MR undergoing MV surgery (derivation, n=1629; validation, n=692) was analysed. Latent class analysis was used to classify patients into subgroups using 15 variables. The primary outcome was all-cause mortality after MV surgery. RESULTS: During follow-up (median 6.0 years), 149 patients (9.1%) died in the derivation cohort. In the univariable Cox analysis, age, female, atrial fibrillation, left ventricular (LV) end-systolic dimension/volumes, LV ejection fraction, left atrial dimension and tricuspid regurgitation peak velocity were significant predictors of mortality following MV surgery. Five distinct phenogroups were identified, three younger groups (group 1-3) and two older groups (group 4-5): group 1, least comorbidities; group 2, men with LV enlargement; group 3, predominantly women with rheumatic MR; group 4, low-risk older patients; and group 5, high-risk older patients. Cumulative survival was the lowest in group 5, followed by groups 3 and 4 (5-year survival for groups 1-5: 98.5%, 96.0%, 91.7%, 95.6% and 83.4%; p<0.001). Phenogroups had similar predictive performance compared with the Mitral Regurgitation International Database score in patients with degenerative MR (3-year C-index, 0.763 vs 0.750, p=0.602). These findings were reproduced in the validation cohort. CONCLUSION: Five phenogroups of patients with severe primary MR with different risk profiles and outcomes were identified. This phenogrouping strategy may improve risk stratification when optimising the timing and type of interventions for severe MR.