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BACKGROUND: Optical flow ratio (OFR) is a novel computational fractional flow reserve derived from optical coherence tomography (OCT). However, the impact of combining post-stenting morphology (OCT) and physiology (OFR) remains largely unknown. METHOD: OCT and OFR were analyzed at the independent core laboratory. Target lesion failure (TLF) was defined as the composite of cardiac death, target lesion myocardial infarction and target lesion revascularization. Suboptimal stent deployment was identified with at least one TLF-related OCT or OFR characteristics. RESULTS: A total of 448 ACS patients (459 vessels) were assessed. Stent expansion<80%, MSA<4.5 mm2 and stent edge lipid-rich plaque and OFR<0.90 were independent predictors of TLR (all p value<0.001). Patients with OCT-suboptimal [adjusted hazard ratio (HR): 7.88, 95% CI: 2.73-22.72, p<0.001] or OFR-suboptimal (adjusted HR: 5.78, 95% CI: 2.54-13.14, p<0.001) stent deployment showed significantly higher risk of TLF compared to those with optimal stent deployment with a significant interaction (pinteraction<0.001). OCT and OFR both-suboptimal stent deployment was confirmed as an independent predictor of TLF (adjusted HR: 9.39, 95% CI: 4.25-20.76, p<0.001). CONCLUSION: Combined OCT and OFR conferred an optimal reclassification of stent deployment, which may aid in decision-making regarding a tailored PCI strategy for optimal stent deployment.
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BACKGROUND: Compared with intravascular ultrasound guidance, there is limited evidence for optical coherence tomography (OCT) guidance during primary percutaneous coronary intervention (pPCI) in ST-segment elevation myocardial infarction (STEMI) patients. AIMS: We investigated the role of OCT in guiding a reperfusion strategy and improving the long-term prognosis of STEMI patients. METHODS: All patients who were diagnosed with STEMI and who underwent pPCI between January 2017 and December 2020 were enrolled and divided into OCT-guided versus angiography-guided cohorts. They had routine follow-up for up to 5 years or until the time of the last known contact. All-cause death and cardiovascular death were designated as the primary and secondary endpoints, respectively. RESULTS: A total of 3,897 patients were enrolled: 2,696 (69.2%) with OCT guidance and 1,201 (30.8%) with angiographic guidance. Patients in the OCT-guided cohort were less often treated with stenting during pPCI (62.6% vs 80.2%; p<0.001). The 5-year cumulative rates of all-cause mortality and cardiovascular mortality in the OCT-guided cohort were 10.4% and 8.0%, respectively, significantly lower than in the angiography-guided cohort (19.0% and 14.1%; both log-rank p<0.001). All 4 multivariate models showed that OCT guidance could significantly reduce 5-year all-cause mortality (hazard ratio [HR] in model 4: 0.689, 95% confidence interval [CI]: 0.551-0.862) and cardiovascular mortality (HR in model 4: 0.692, 95% CI: 0.536-0.895). After propensity score matching, the benefits of OCT guidance were consistent in terms of all-cause mortality (HR: 0.707, 95% CI: 0.548-0.913) and cardiovascular mortality (HR: 0.709, 95% CI: 0.526-0.955). CONCLUSIONS: Compared with angiography alone, OCT guidance may change reperfusion strategies and lead to better long-term survival in STEMI patients undergoing pPCI. Findings in the current observational study should be further corroborated in randomised trials.
Subject(s)
Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Tomography, Optical Coherence , Humans , Percutaneous Coronary Intervention/methods , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/mortality , Male , Female , Middle Aged , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/surgery , Aged , Follow-Up Studies , Treatment Outcome , Coronary AngiographyABSTRACT
Background: Endothelial dysfunction, characterized by impaired flow-mediated vasodilation (FMD), is associated with atherosclerosis. However, the relationship between FMD, plaque morphology, and clinical outcomes in patients with acute coronary syndrome (ACS) remains underexplored. This study aims to investigate the influence of FMD on the morphology of culprit plaques and subsequent clinical outcomes in patients with ACS. Methods: This study enrolled 426 of 2482 patients who presented with ACS and subsequently underwent both preintervention FMD and optical coherence tomography (OCT) between May 2020 and July 2022. Impaired FMD was defined as an FMD% less than 7.0%. Major adverse cardiac events (MACEs) included cardiac death, nonfatal myocardial infarction, revascularization, or rehospitalization for angina. Results: Within a one-year follow-up, 34 (8.0%) patients experienced MACEs. The median FMD% was 4.0 (interquartile range 2.6-7.0). Among the patients, 225 (52.8%) were diagnosed with plaque rupture (PR), 161 (37.8%) with plaque erosion (PE), and 25 (5.9%) with calcified nodules (CN). Impaired FMD was found to be associated with plaque rupture (odds ratio [OR] = 4.22, 95% confidence interval [CI]: 2.07-6.72, p = 0.012) after adjusting for potential confounding factors. Furthermore, impaired FMD was linked to an increased incidence of MACEs (hazard ratio [HR] = 3.12, 95% CI: 1.27-6.58, p = 0.039). Conclusions: Impaired FMD was observed in three quarters of ACS patients and can serve as a noninvasive predictor of plaque rupture and risk for future adverse cardiac outcomes.
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BACKGROUND: Tar is the main toxic of cigarettes, and its effect on atherosclerosis progression and the underlying mechanisms remain largely unknown. Vascular smooth muscle cells (VSMCs) play a key role in atherogenesis and plaque vulnerability. The present study sought to investigate the mechanism of atherosclerosis progression through tar-induced VSMC necroptosis, a recently described form of necrosis. METHODS: The effect of tar on atherosclerosis progression and VSMC necroptosis was examined in ApoE-/- mice and cultured VSMCs. The role of necroptosis in tar-induced plaque development was evaluated in RIPK3-deletion mice (ApoE-/-RIPK3-/-). The key proteins of necroptosis in carotid plaques of smokers and non-smokers were also examined. Quantitative proteomics of mice aortas was conducted to further investigate the underlying mechanism. Pharmacological approaches were then applied to modulate the expression of targets to verify the regulatory process of tar-induced necroptosis. RESULTS: Tar administration led to increased atherosclerotic plaque area and reduced collagen and VSMCs in ApoE-/- mice. The expression of RIPK1ãRIPK3ãand MLKL in VSMCs of plaques were all increased in tar-exposed mice and smokers. RIPK3 deletion protected against VSMC loss and plaque progression stimulated by tar. In mechanistic studies, quantitative proteomics analysis of ApoE-/- mice aortas suggested that tar triggered endoplasmic reticulum (ER) stress. PERK-eIF2α-CHOP axis was activated in tar-treated VSMCs and atherosclerotic plaque. Inhibition of ER stress using 4PBA significantly reduced plaque progression and VSMC necroptosis. Further study revealed that ER stress resulted in calcium (Ca2+) release into mitochondria and cytoplasm. Elevated Ca2+ levels lead to mitochondrial dysfunction and excessive reactive oxygen species (ROS) production, which consequently promote RIPK3-dependent necroptosis. In addition, Ca2+/calmodulin-dependent protein kinase II (CaMKII) activated by cytosolic Ca2+ overload binds to RIPK3, accounting for necroptosis. CONCLUSION: The findings revealed that cigarette tar promoted atherosclerosis progression by inducing RIPK3-dependent VSMC necroptosis and identified novel avenues of ER stress and Ca2+ overload.
Subject(s)
Atherosclerosis , Plaque, Atherosclerotic , Tars , Mice , Animals , Plaque, Atherosclerotic/metabolism , Muscle, Smooth, Vascular , Necroptosis , Atherosclerosis/metabolism , Endoplasmic Reticulum Stress , Apolipoproteins E/metabolism , Myocytes, Smooth Muscle/metabolismABSTRACT
BACKGROUND: Micheliolide (MCL), which is the active metabolite of parthenolide, has demonstrated promising clinical application potential. However, the effects and underlying mechanisms of MCL on atherosclerosis are still unclear. METHOD: ApoE-/- mice were fed with high fat diet, with or without MCL oral administration, then the plaque area, lipid deposition and collagen content were determined. In vitro, MCL was used to pretreat macrophages combined by ox-LDL, the levels of ferroptosis related proteins, NRF2 activation, mitochondrial function and oxidative stress were detected. RESULTS: MCL administration significantly attenuated atherosclerotic plaque progress, which characteristics with decreased plaque area, less lipid deposition and increased collagen. Compared with HD group, the level of GPX4 and xCT in atherosclerotic root macrophages were increased in MCL group obviously. In vitro experiment demonstrated that MCL increased GPX4 and xCT level, improved mitochondrial function, attenuated oxidative stress and inhibited lipid peroxidation to suppress macrophage ferroptosis induced with ox-LDL. Moreover, MCL inhibited KEAP1/NRF2 complex formation and enhanced NRF2 nucleus translocation, while the protective effect of MCL on macrophage ferroptosis was abolished by NRF2 inhibition. Additionally, molecular docking suggests that MCL may bind to the Arg483 site of KEAP1, which also contributes to KEAP1/NRF2 binding. Furthermore, Transfection Arg483 (KEAP1-R483S) mutant plasmid can abrogate the anti-ferroptosis and anti-oxidative effects of MC in macrophages. KEAP1-R483S mutation also limited the protective effect of MCL on atherosclerosis progress and macrophage ferroptosis in ApoE-/- mice. CONCLUSION: MCL suppressed atherosclerosis by inhibiting macrophage ferroptosis via activating NRF2 pathway, the related mechanism is through binding to the Arg483 site of KEAP1 competitively.
Subject(s)
Atherosclerosis , Ferroptosis , Plaque, Atherosclerotic , Sesquiterpenes, Guaiane , Animals , Mice , NF-E2-Related Factor 2/metabolism , Kelch-Like ECH-Associated Protein 1/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , Molecular Docking Simulation , Atherosclerosis/drug therapy , Atherosclerosis/genetics , Atherosclerosis/metabolism , Plaque, Atherosclerotic/metabolism , Macrophages/metabolism , Apolipoproteins E/genetics , Collagen/metabolismABSTRACT
Salt-sensitivity hypertension (SSHTN) is an independent predictor for cardiovascular mortality. VEGFC has been reported to be a protective role in SSHTN and hypertensive kidney injury. However, the underlying mechanisms remain largely unclear. The current study aimed to explore the protective effects and mechanisms of VEGFC against SSHTN and hypertensive nephropathy. Here, we reported that VEGFC attenuated high blood pressure as well as protected against renal inflammation and fibrosis in SSHTN mice. Moreover, VEGFC suppressed the activation of renal NLRP3 inflammasome in SSHTN mice. In vitro, we found VEGFC inhibited NLRP3 inflammasome activation, meanwhile, upregulated autophagy in high-salt-induced macrophages, while these effects were reversed by an autophagy inhibitor 3MA. Furthermore, in vivo, 3MA pretreatment weakened the protective effects of VEGFC on SSHTN and hypertensive nephropathy. Mechanistically, VEGF receptor 3 (VEGFR3) kinase domain activated AMPK by promoting the phosphorylation at Thr183 via binding to AMPK, thus enhancing autophagy activity in the context of high-salt-induced macrophages. These findings indicated that VEGFC inhibited NLRP3 inflammasome activation by promoting VEGFR3-AMPK-dependent autophagy pathway in high-salt-induced macrophages, which provided a mechanistic basis for the therapeutic target in SSHTN and hypertensive kidney injury.
Subject(s)
Hypertension , Inflammasomes , Mice , Animals , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , AMP-Activated Protein Kinases/metabolism , AutophagyABSTRACT
Pyroptosis plays an important role in inflammatory diseases such as viral hepatitis and atherosclerosis. Apigenin exhibits various bioactivities, particularly anti-inflammation, but its effect on pyroptosis remains unclear. The aim of this study is to investigate the effect of apigenin on pyroptosis and explore its potential against inflammatory diseases. THP-1 macrophages treated by lipopolysaccharides/adenosine 5'-triphosphate were used as the in vitro pyroptosis model. Western blot was used to detect the expression of NLRP3 inflammasome components and key regulators. Immunofluorescence was used to observe ROS production and intracellular location of p65. The potential of apigenin against inflammatory diseases was evaluated using atherosclerotic mice. Plaque progression was observed by pathological staining. Immunofluorescence was used to observe the expression of NLRP3 inflammasome components in plaques. The results showed that apigenin inhibited NLRP3 inflammasome activation. Apigenin reduced ROS overproduction and inhibited p65 nuclear translocation. Additionally, apigenin decreased the expression of NLRP3 inflammasome components in the plaque. Plaque progression was inhibited by apigenin. In conclusion, apigenin exhibited a preventive effect on macrophage pyroptosis by reducing oxidative stress and inhibiting the NF-κB pathway. Apigenin may alleviate atherosclerosis at least partially by inhibiting macrophage pyroptosis. These findings suggest apigenin to be a promising therapeutic agent for inflammatory diseases.
Subject(s)
Atherosclerosis , NF-kappa B , Mice , Animals , NF-kappa B/metabolism , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroptosis/physiology , Apigenin/pharmacology , Reactive Oxygen Species/metabolism , Signal Transduction , Oxidative Stress/physiology , Macrophages , Atherosclerosis/drug therapy , Atherosclerosis/metabolismABSTRACT
Background: As a novel lipoprotein ratio, baseline low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (LHR) is closely related to the clinical outcomes of acute coronary syndromes (ACS) after percutaneous coronary intervention. However, the pathophysiological impact of achieved LHR (aLHR) on the evolution of non-culprit lipid-rich plaques has not been systematically explored. Methods: Between September 2013 and December 2018, ACS patients with both baseline and 1-year follow-up optical coherence tomography (OCT) examinations were included in current study. They were divided into two groups according to the median value of aLHR at 1 year. Results: Overall, 132 patients with 215 lipid-rich plaques were enrolled, with a median aLHR: 1.62. There were thinner fibrous cap thickness (FCT) (133.3 [70.0-180.0] µm vs. 160.0 [100.0-208.3] µm, p = 0.025) and higher prevalence of thin-cap fibroatheroma (TCFA) (24 [22.4%] vs. 13 [12.0%], p = 0.044) and CLIMA-defined high-risk plaques (12 [11.2%] vs. 3[2.8%], p = 0.015) in the high aLHR group at 1 year. Compared with other serum lipid indexes, aLHR showed the best robust correlation with the evolution of plaque vulnerability in both unadjusted and adjusted analyses. Cut-off value of aLHR to predict the progression of maximal lipid arc and FCT was 1.51. In the adjusted model, aLHR ≥1.51 was an independent predictor of TCFA [odds ratio (OR): 3.008, 95% CI: 1.370 to 6.605, p = 0.006] at 1 year. Conclusions: aLHR correlates well with the evolution of lipid-rich plaques and vulnerable phenotypes at 1-year follow-up, which might be an important and convenient serum indicator in the secondary prevention of ACS.
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BACKGROUND: Plaque rupture (PR) and plaque erosion (PE) are 2 distinct, different, and most common culprit lesion morphologies responsible for acute coronary syndrome (ACS). However, the prevalence, distribution, and characteristics of peripheral atherosclerosis in ACS patients with PR vs PE has never been studied. The aim of this study was to assess peripheral atherosclerosis burden and vulnerability evaluated by vascular ultrasound in ACS patients with coronary PR vs PE identified by optical coherence tomography (OCT). METHODS: Between October 2018 and December 2019, 297 ACS patients who underwent preintervention OCT examination of the culprit coronary artery were enrolled. Peripheral ultrasound examinations of carotid, femoral, and popliteal arteries were performed before discharge. RESULTS: Overall, 265 of 297 (89.2%) patients had at least one atherosclerotic plaque in a peripheral arterial bed. Compared with coronary PE, patients with coronary PR had a higher prevalence of peripheral atherosclerotic plaques (93.4% vs 79.1%, P < .001), regardless of location: carotid, femoral, or popliteal arteries. The number of peripheral plaques per patient was significantly larger in the coronary PR group than coronary PE (4 [2-7] vs 2 [1-5], P < .001). Additionally, there was a greater prevalence of peripheral vulnerable characteristics including plaque surface irregularity, heterogeneous plaque, and calcification in patients with coronary PR vs PE. CONCLUSIONS: Peripheral atherosclerosis exists commonly in patients presenting with ACS. Patients with coronary PR had greater peripheral atherosclerosis burden and more peripheral vulnerability compared to those with coronary PE, suggesting that comprehensive evaluation of peripheral atherosclerosis and multidisciplinary cooperative management maybe necessary, especially in patients with PR. TRIAL REGISTRATION: clinicaltrials.gov (NCT03971864).
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BACKGROUND: Elevated plasma homocysteine levels, known as hyperhomocysteinemia, have been identified as an independent risk factor for atherosclerosis and related cardiovascular diseases. Macrophage pyroptosis-mediated inflammation is crucial in the development of atherosclerosis, but the underlying mechanisms remain unclear. METHODS: A hyperhomocysteinemia atherosclerotic model with ApoE-/- mice fed with a high-methionine diet was constructed to investigate the role of plasma homocysteine in atherosclerosis. THP-1-derived macrophages were used to investigate the mechanisms by which Hcy regulates pyroptosis. RESULTS: We found that hyperhomocysteinemia resulted in larger atherosclerotic plaques and more secretion of inflammatory cytokines, while these effects were attenuated in Caspase-1 knockdown mice. Likewise, in vitro experiments demonstrated that treatment of macrophages with homocysteine resulted in NLRP3 inflammasome activation and pyroptosis, as evidenced by cleavage of Caspase-1, production of downstream IL-1ß, elevation of lactate dehydrogenase activity, and extensive propidium iodide-positive staining of cells. These were all inhibited by Caspase-1 inhibitor. In addition, excessive generation of reactive oxygen species was associated with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential and ATP synthesis. Moreover, further experiments revealed that homocysteine induced endoplasmic reticulum stress, enhanced communication between the endoplasmic reticulum and mitochondria, and consequently contributed to calcium disorder. Furthermore, the endoplasmic reticulum stress inhibitor, 4PBA, the calcium chelator, BAPTA, and calcium channel inhibitor, 2-APB significantly improved macrophage pyroptosis. CONCLUSION: Homocysteine accelerates atherosclerosis progression by enhancing macrophages pyroptosis via promoting endoplasmic reticulum stress, endoplasmic reticulum-mitochondria coupling, and disturbing of calcium disorder.
Subject(s)
Atherosclerosis , Hyperhomocysteinemia , Animals , Mice , Pyroptosis , Calcium , Caspase 1 , Endoplasmic Reticulum StressABSTRACT
BACKGROUND AND AIMS: The prevalence of acute coronary syndrome (ACS) patients with cancer history is increasing and it is associated with higher mortality. However, there is limited evidence on the characteristics of coronary plaque in ACS patients with cancer history. This study explored the pancoronary plaque characteristics in ACS patients with cancer history by optical coherence tomography (OCT). METHODS: A total of 306 ACS patients treated by 3-vessel OCT at the time of percutaneous coronary intervention (PCI) were included, retrospectively. Patients were divided into two groups according to the presence or absence of cancer history: one group with cancer history (n = 98) and a matched group without cancer history (n = 208). RESULTS: A total of 314 culprit lesions and 514 nonculprit lesions were identified by OCT in this study. In culprit lesions, ACS patients with cancer history had higher incidence of thin cap fibroatheroma (TCFA) (p = 0.016), cholesterol crystals (p = 0.028), calcification (p = 0.001) and thrombus (p = 0.001), and had thinner fibrous cap thickness (FCT) (p = 0.011), greater maximum lipid arc (p = 0.042) and lipid index (p < 0.001), compared to matched ACS patients without cancer history. In nonculprit lesions, ACS patients with cancer history had higher prevalence of high-risk plaque (14.7% vs. 7.7%, p = 0.017), nonculprit rupture (14.7% vs. 6.3%, p = 0.003), and TCFA (52.2% vs. 28.3%, p < 0.001), and had higher incidence of calcification (p = 0.003), thrombus (p = 0.029), cholesterol crystals (p = 0.002) and microchannels (p = 0.029). These non-culprit lesions had longer lesion length (p = 0.001), thinner FCT (p < 0.001), greater maximum lipid arc (p = 0.016) and lipid index (p < 0.001). CONCLUSIONS: ACS patients with cancer history showed more high-risk plaque features in culprit and nonculprit lesions, compared with ACS patients without cancer history. Therefore, ACS patients with cancer history may have greater pancoronary vulnerability. This may predict a poorer prognosis for ACS patients with cancer history.
Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Neoplasms , Percutaneous Coronary Intervention , Plaque, Atherosclerotic , Thrombosis , Humans , Plaque, Atherosclerotic/pathology , Acute Coronary Syndrome/complications , Acute Coronary Syndrome/diagnostic imaging , Acute Coronary Syndrome/epidemiology , Retrospective Studies , Fibrosis , Neoplasms/complications , Neoplasms/epidemiology , Neoplasms/pathology , Thrombosis/pathology , Cholesterol , Lipids , Tomography, Optical Coherence/methods , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Coronary Angiography , Coronary Artery Disease/pathologyABSTRACT
Oxidative stress and lipid metabolism disorder caused by estrogen deficiency are regarded as the main causes of postmenopausal atherosclerosis, but the underlying mechanisms remain still unclear. In this study, ovariectomized (OVX) female ApoE-/- mice fed with high-fat diet were used to imitate postmenopausal atherosclerosis. The atherosclerosis progression was significantly accelerated in OVX mice, accompanied by the upregulation of ferroptosis indicators, including increased lipid peroxidation and iron deposition in the plaque and the plasma. While both estradiol (E2) and ferroptosis inhibitor ferrostatin-1 alleviated atherosclerosis in OVX mice, with the inhibition of lipid peroxidation and iron deposition, as well as the upregulation of xCT and GPX4, especially in endothelial cells. We further investigated the effects of E2 on ferroptosis in endothelial cells induced by oxidized-low-density lipoprotein or ferroptosis inducer Erastin. It was found that E2 exhibited anti-ferroptosis effect through antioxidative functions, including improving mitochondrial dysfunction and upregulating GPX4 expression. Mechanistically, NRF2 inhibition attenuated the effect of E2 against ferroptosis as well as the upregulation of GPX4. Our findings revealed that endothelial cell ferroptosis played a pivotal role in postmenopausal atherosclerosis progression, and the NRF2/GPX4 pathway activation contributed to the protection of E2 against endothelial cell ferroptosis.
Subject(s)
Atherosclerosis , NF-E2-Related Factor 2 , Animals , Female , Mice , Endothelial Cells , Estrogens/deficiency , Iron , PostmenopauseSubject(s)
Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Humans , ST Elevation Myocardial Infarction/diagnostic imaging , ST Elevation Myocardial Infarction/therapy , Follow-Up Studies , Predictive Value of Tests , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/therapy , Reperfusion , Treatment Outcome , Myocardial Reperfusion , Percutaneous Coronary Intervention/adverse effectsABSTRACT
BACKGROUND: Myocardial infarction with nonobstructive coronary artery (MINOCA) is a heterogeneous syndrome caused by different pathophysiologic mechanisms. There is limited evidence regarding prognosis of patients with MINOCA caused by different mechanisms. OBJECTIVES: The present study aimed to assess the underlying mechanisms of MINOCA by optical coherence tomography (OCT) and to correlate with clinical outcomes. METHODS: Patients with MINOCA were divided into 2 groups based on OCT findings: atherosclerotic MINOCA (Ath-MINOCA) and nonatherosclerotic MINOCA (non-Ath-MINOCA). Major adverse cardiac events (MACE) were defined as cardiac death, nonfatal MI, target lesion revascularization, stroke, and rehospitalization for unstable or progressive angina. RESULTS: Among 7,423 patients with a clinical diagnosis of MI who underwent angiography, 190 of 294 MINOCA were studied using OCT. The causes of Ath-MINOCA (n = 99, 52.1%) were plaque erosion (n = 64, 33.7%), plaque rupture (n = 33, 17.4%), and calcified nodule (n = 2, 1.1%) whereas the causes of non-Ath-MINOCA (n = 91, 47.9%) were spontaneous coronary artery dissection (n = 8, 4.2%), coronary spasm (n = 9, 4.7%), and unclassified cause (n = 74, 38.9%). The 1-year MACE was 15.3% for Ath-MINOCA vs 4.5% for non-Ath-MINOCA (P = 0.015). An atherosclerotic cause was an independent predictor of MACE (HR: 5.36 [95% CI: 1.08-26.55]; P = 0.040), mainly driven by target lesion revascularization and rehospitalization, despite the composite endpoint including cardiac death and MI showing no difference. CONCLUSIONS: OCT identified a cause in 61.1% of MINOCA, in which Ath-MINOCA represents an important and distinct MINOCA subset. Ath-MINOCA were more common and associated with worse outcomes. (Incidence Rate of Heart Failure After Acute Myocardial Infarction With Optimal Treatment; NCT03297164; Paradigm Shift in the Treatment of Patients With ACS; NCT02041650).
Subject(s)
Coronary Artery Disease , Myocardial Infarction , Humans , MINOCA , Tomography, Optical Coherence/adverse effects , Coronary Angiography/adverse effects , Predictive Value of Tests , Myocardial Infarction/etiology , Prognosis , Death , Coronary Vessels/pathology , Risk Factors , Coronary Artery Disease/pathologyABSTRACT
Background: Artificial intelligence enables simultaneous evaluation of plaque morphology and computational physiology from optical coherence tomography (OCT). Objectives: This study sought to appraise the predictive value of major adverse cardiovascular events (MACE) by combined plaque morphology and computational physiology. Methods: A total of 604 patients with acute coronary syndrome who underwent OCT imaging in ≥1 nonculprit vessel during index coronary angiography were retrospectively enrolled. A novel morphologic index, named the lipid-to-cap ratio (LCR), and a functional parameter to evaluate the physiologic significance of coronary stenosis from OCT, namely, the optical flow ratio (OFR), were calculated from OCT, together with classical morphologic parameters, like thin-cap fibroatheroma (TCFA) and minimal lumen area. Results: The 2-year cumulative incidence of a composite of nonculprit vessel-related cardiac death, cardiac arrest, acute myocardial infarction, and ischemia-driven revascularization (NCV-MACE) at 2 years was 4.3%. Both LCR (area under the curve [AUC]: 0.826; 95% CI: 0.793-0.855) and OFR (AUC: 0.838; 95% CI: 0.806-0.866) were superior to minimal lumen area (AUC: 0.618; 95% CI: 0.578-0.657) in predicting NCV-MACE at 2 years. Patients with both an LCR of >0.33 and an OFR of ≤0.84 had significantly higher risk of NCV-MACE at 2 years than patients in whom at least 1 of these 2 parameters was normal (HR: 42.73; 95% CI: 12.80-142.60; P < 0.001). The combination of thin-cap fibroatheroma and OFR also identified patients at higher risk of future events (HR: 6.58; 95% CI: 2.83-15.33; P < 0.001). Conclusions: The combination of LCR with OFR permits the identification of a subgroup of patients with 43-fold higher risk of recurrent cardiovascular events in the nonculprit vessels after acute coronary syndrome.
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BACKGROUND: Calcified plaque is thought to adversely impact outcomes after percutaneous coronary intervention (PCI). This study sought to evaluate the impact of nodular calcification in patients with acute coronary syndrome treated with primary percutaneous coronary intervention. METHODS: Using optical coherence tomography (OCT), 500 culprit plaques with calcification were analyzed from 495 acute coronary syndrome (ACS) patients on whom PCI was performed. Based on morphology, we classified calcification into two subtypes: nodular calcification and non-nodular calcification. Nodular calcification was defined as protruding mass with an irregular surface, high backscattering, and signal attenuation while non-nodular calcification was defined as an area with low backscattering heterogeneous region with a well-delineated border without protrusion into the lumen on OCT. RESULTS: Calcified culprit plaques were divided into nodular calcification group (n = 238) and non-nodular calcification group (n = 262). Patients with nodular calcification were older (p < 0.001) and had lower left ventricular ejection fraction (p = 0.006) compared to patients with non-nodular calcification. Minimum stent area (5.0 (3.9, 6.3) mm2 vs. 5.4 (4.2, 6.7) mm2, p = 0.011) and stent expansion (70 (62.7, 81.8) % vs. 75 (65.2, 86.6) %, p = 0.004) were significantly smaller in the nodular calcification group than in the non-nodular calcification group. Stent under-expansion was most frequent (p = 0.003) in the nodular calcification group. CONCLUSION: This study demonstrate that the presence of nodular calcification is associated with a smaller minimum stent area and a higher incidence of stent under-expansion. Lesions with nodular calcification may be at risk of stent under-expansion.
Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Percutaneous Coronary Intervention , Plaque, Atherosclerotic , Vascular Calcification , Acute Coronary Syndrome/diagnostic imaging , Acute Coronary Syndrome/epidemiology , Acute Coronary Syndrome/therapy , Coronary Angiography/methods , Coronary Artery Disease/therapy , Coronary Vessels/diagnostic imaging , Coronary Vessels/pathology , Humans , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Stents , Stroke Volume , Tomography, Optical Coherence/methods , Vascular Calcification/diagnostic imaging , Vascular Calcification/epidemiology , Vascular Calcification/therapy , Ventricular Function, LeftABSTRACT
BACKGROUND: Clonal haematopoiesis driven by mutations in DNMT3A or TET2 has recently been identified as a new risk factor for cardiovascular disease. Experimental studies suggest that these mutations may enhance inflammation which accelerates the disease progression. We aim to investigate the prevalence of mutations in DNMT3A and TET2 and their association with prognosis of patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Targeted deep sequencing for DNMT3A and TET2 and inflammatory cytokines (IL-1ß, IL-6, TNF-α, INF-γ) were analyzed in 485 patients with STEMI. Major adverse cardiac events (MACE) was a composite of death, myocardial infarction, stroke, or hospitalization due to heart failure. FINDINGS: Patients carrying DNMT3A- or TET2-CH-driver mutations with a variant allele frequency (VAF) ≥2% were found in 12.4% (60 of 485) of STEMI patients and experienced an increased incidence of the death (30.9% vs 15.5%, P = 0.001) and MACE (44.5% vs 21.8%, P < 0.001) compared to those who did not, during a median follow up of 3.0 (interquartile range: 2.4-3.4) years. After adjusting for confounders, mutation remained an independent predictor of death (HR = 1.967, 95% CI 1.103-3.507, P = 0.022) and MACE (HR = 1.833, 95% CI 1.154-2.912, P = 0.010). Concentrations of plasma IL-1ß (P = 0.010) and IL-6 (P = 0.011) were significantly elevated in DNMT3A/TET2 VAF≥2% group. INTERPRETATION: DNMT3A- or TET2-CH-driver mutations with a VAF≥2% were observed in over 10% STEMI patients, and were significantly associated with poorer prognosis, which might be explained by higher levels of inflammatory cytokines in mutations carriers. FUNDING: National Natural Science Foundation of China; National Key R&D Program of China.
Subject(s)
DNA Methyltransferase 3A , DNA-Binding Proteins , Dioxygenases , ST Elevation Myocardial Infarction , Clonal Hematopoiesis , Cytokines , DNA Methyltransferase 3A/genetics , DNA-Binding Proteins/genetics , Dioxygenases/genetics , Humans , Mutation , Prevalence , Prognosis , Proto-Oncogene Proteins/genetics , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/geneticsABSTRACT
Coronary calcification is a strong indicator of coronary artery disease and a key determinant of the outcome of percutaneous coronary intervention. We propose a fully automated method to segment and quantify coronary calcification in intravascular OCT (IVOCT) images based on convolutional neural networks (CNN). All possible calcified plaques were segmented from IVOCT pullbacks using a spatial-temporal encoder-decoder network by exploiting the 3D continuity information of the plaques, which were then screened and classified by a DenseNet network to reduce false positives. A novel data augmentation method based on the IVOCT image acquisition pattern was also proposed to improve the performance and robustness of the segmentation. Clinically relevant metrics including calcification area, depth, angle, thickness, volume, and stent-deployment calcification score, were automatically computed. 13844 IVOCT images with 2627 calcification slices from 45 clinical OCT pullbacks were collected and used to train and test the model. The proposed method performed significantly better than existing state-of-the-art 2D and 3D CNN methods. The data augmentation method improved the Dice similarity coefficient for calcification segmentation from 0.615±0.332 to 0.756±0.222, reaching human-level inter-observer agreement. Our proposed region-based classifier improved image-level calcification classification precision and F1-score from 0.725±0.071 and 0.791±0.041 to 0.964±0.002 and 0.883±0.008, respectively. Bland-Altman analysis showed close agreement between manual and automatic calcification measurements. Our proposed method is valuable for automated assessment of coronary calcification lesions and in-procedure planning of stent deployment.