Concertina effect mimicking plaque rupture in a patient presenting with acute coronary syndrome

Acute coronary syndromes

To the Editor: Rioufol et al1 recently reported a lower incidence of plaque rupture in culprit arteries than in non-culprit arteries (37.5% versus 79%) in acute coronary syndrome (ACS). The low incidence in culprit arteries was explained by thrombi that masked underlying ulcerations, but findings suggest that plaque rupture/thromboses do not directly induce symptoms in ACS (or ACS/infarction). There are other problems with the plaque rupture/thromboses mechanism. These include low (around 25%) incidences of thromboses in ACS,2,3 failure of thrombolysis to benefit non-ST-segment elevation infarction,3 rising incidence of thromboses over time in infarction,2,3 common occurrence of asymptomatic plaque rupture,3 failure of platelet glycoprotein IIb/IIIa receptor blockade to benefit most cases of ACS,4 and apparent inability of thromboses in very stenotic arteries to explain infarction.2,3 To my knowledge, nobody has seen plaque rupture …

Recent hemodynamic studies have demonstrated that progression of coronary atherosclerosis occurs at low wall share-stress site, whereas plaque rupture frequently occurs at high share stress site. It is well recognized that wall shear stress is relatively low along the outer walls of the bifurcation. We investigated consecutive 140 patients (77 with acute coronary syndrome (ACS) and 63 with chronic coronary syndrome (CCS) performed PCI for LAD proximal lesions (AHA seg.6) from January 2016 to December 2019. In CCS group, entry criteria included stenosis of at least 90% in the LAD proximal lesion or at least 70% in the LAD proximal lesion and objective evidence of myocardial ischemia (inducible ischemia with either exercise or pharmacologic vasodilator stress or with pressure wire). Exclusion criteria were patients with maintenance dialysis, chronic total occlusion lesions, in-stent restenosis, and clinically diagnosed unstable angina without troponin I elevation. We measured the distance from LMT distal carina to the culprit site (Distance) and plaque location (Location) with intravascular ultrasound and angle between LMT and LAD with cardiovascular angiography analysis system (CAAS) (Angle). The two groups were generally well balanced with regard to baseline clinical characteristics. The mean (±SD) age of the patients was 69.0±11.8 years, and 75% were men. Medication at baseline was also similar between two groups except higher prevalence of statin prescription in CCS group. The Distance was shorter and Angle was steeper in CCS group than in ACS group. The number of patients with Angle less than 150 degrees and with Location in the lateral wall side was much more in CCS group. In this study, plaques in CCS were frequently observed at low shear stress site, whereas those in ACS at high shear stress site. Plaque progression in CCS may be associated with low wall shear stress, and high shear stress may play key role in plaque rupture in ACS. This anatomical difference can partly explain the different mechanisms of onset between of ACS and CCS. Funding Acknowledgement Type of funding sources: None. Anatomical differenceCharacteristics and results

Coronary heart disease is the leading cause of mortality and morbidity in industrialized countries, in men as well as in women. Women have their first cardiac event 6 to 10 years later than men do. Whereas the cardiovascular death rates are declining in men, they remain constant in women. In cardiovascular studies with age limits, women are naturally the minority, amounting to <40%. It is well known that distinct gender differences exist in terms of presentation of symptoms, validity of diagnostic tests, drug side effects, and complications. With respect to cardiac risk factors, women have higher rates of diabetes and hypertension but are less frequently smokers. See p 580 Women with acute coronary syndrome (ACS) call later for professional help and present more frequently with atypical symptoms, such as abnormal pain locations, nausea, vomiting, fatigue, and dyspnea. We can only speculate on the reasons for these differences, but they could be related to different pain perception, older age, or other comorbidities. ECG as the first-line diagnostic tool in ACS is also less reliable in females presenting to emergency rooms. There are less frequent ST elevations and higher rates of ST depressions and T-wave inversions, as well as nonspecific alterations. The type of ischemic event shows gender-specific differences. According to studies such as GUSTO IIb (Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes),1 TIMI IIIB (Thrombolysis In Myocardial Infarction),2 and the Euro Heart Survey,3 women present more frequently with unstable angina and non–ST-elevation myocardial infarction (NSTEMI), whereas men have ACS with ST elevation (STEMI). The outcome in NSTEMI appears equal, but in STEMI, mortality is higher in women. Women seem to be evaluated less intensively, which is possibly related to the perception that coronary artery disease is predominately a male disease. Cardiac-specific biochemical …

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Clinicians have become increasingly sophisticated in their application of cardiac biomarkers in the management of acute coronary syndromes (ACS). In the 1950s, clinical investigators first reported that proteins released from necrotic cardiac myocytes could be detected in the serum and could aid in the diagnosis of acute myocardial infarction.1 The ensuing 40 years witnessed progressive improvement in the cardiac tissue-specificity of biomarkers of myocardial necrosis and a corresponding enhancement in the clinical sensitivity and specificity of their use for establishing the diagnosis of acute myocardial infarction. Over the past decade, the emergence of convincing evidence for the value of cardiac troponin in guiding therapy has dramatically accelerated the integration of cardiac biomarkers into clinical decision-making for patients with ACS.2 Concurrently, advances in our understanding of the pathogenesis and consequences of acute coronary atherothrombosis have stimulated the development of new biomarkers and created the opportunity for an expanded role of multiple biomarkers, some old and others new, in the classification and individualization of treatment for ACS.3,4 The report by James et al5 in the present issue of Circulation adds substantially to the accumulating evidence that a multimarker strategy, employing a pathobiologically diverse set of biomarkers,3 is likely to add importantly to cardiac-specific troponin alone in the risk assessment of patients with ACS. See p 275 ACS is a complex syndrome with multiple causes, analogous to anemia or hypertension.6 As such, treatment is likely to be most effective when directed at the underlying cause of the disease. Five principal causes of ACS have been described; these include (1) plaque rupture with acute thrombosis, (2) progressive mechanical obstruction, (3) inflammation, (4) secondary unstable angina, and (5) dynamic obstruction (coronary vasoconstriction).7 It is rare that any of these contributors exists in isolation. However, patients with ACS may …

Background Although previous studies have reported that patients with a history of cancer have 2–3 times higher risks for acute coronary syndrome (ACS), morphological culprit plaque characteristics in ACS patients with a cancer history and their relations with clinical outcomes remain unknown. Methods The Kobe University ACS-OCT registry is a multi-center registry of consecutive ACS patients who underwent OCT-guided emergent PCI in Japanese four centers. All patients were categorized into the patients without a history of cancer (non-cancer), those with a history of cancer who diagnosed more than one year before ACS (historical), and those with ongoing cancer treatment or diagnosis within one year before ACS (current). ACS culprit lesions were classified into plaque rupture (PR), plaque erosion (PE), and calcified nodule (CN) according to morphological features by OCT and clinical events were collected after the onset of ACS. Results Among 436 patients, 63 patients (14.4%) had a history of cancer or ongoing treatment of cancer (cancer patients). Cancer patients were significantly older than non-cancer patients (73.4±9.4 vs. 66.9±12.9, p=0.001), and non-ST segment elevation ACS was more frequently observed in cancer patients than in non-cancer patients (57.1% vs. 43.2%, p=0.039). Regarding the ACS culprit lesion, the frequency of PR was significantly lower and the frequencies of PE and CN were significantly higher in the cancer patients than in the non-cancer patients (Figure A1). The cumulative incidence of major adverse cardiovascular event (MACE: composite of cardiac death, non-fatal myocardial infarction, and any revascularization, stroke, and heart failure with admission) after the onset of ACS in cancer patients was significantly higher than that in the non-cancer patients (Figure B1). When the cancer patients were categorized into the historical and the current cancer patients, the frequency of PE was higher in the current and the historical cancer patients than the non-cancer patients. Also, the incidence of CN was significantly higher in the historical cancer patients than others (Figure A2). The cumulative incidence of MACE was significantly higher in the current cancer patients, followed by historical and non-cancer patients (Figure B2). Cox regression analyses demonstrated that the non-PR lesion (hazard ratio (HR) 0.65, 0.46–0.94, p=0.021), patients with multivessel disease (HR 2.55, 1.79–3.64, p&amp;lt;0.001), older patients (HR 1.02, 1.00–1.03, p=0.043) were independently associated with MACE after ACS. Moreover, multivariate analysis demonstrated that cancer history (HR 4.64, 2.34–9.21, p&amp;lt;0.001) and non-ST segment elevation ACS (HR 0.66, 2.34–9.21, p=0.038) were independently associated with non-PR lesion. Conclusions The present study revealed the difference in morphological plaque characteristics between cancer and non-cancer patients, which might explain potential underlying mechanisms for worse outcomes in cancer patients. Funding Acknowledgement Type of funding source: None

Lipoprotein associated phospholipase A2 (Lp-PLA2) may play a role in the formation of vulnerable atherosclerotic plaques and plaque rupture. Its plasma distribution and mass in subjects with acute coronary syndromes (ACS) are not characterized. The objective of this study was to examine plasma levels and distribution of Lp-PLA2 in patient with ACS. We compared plasma levels of LP-PLA2 in 23 patients within 48 hours of presentation of an ACS (visit 1) and 12 weeks after (visit 2), in 24 patients with chronic, stable coronary artery disease (sCAD) and in normal healthy controls. The distribution of Lp-PLA2 was determined by ultracentrifugation (UTC), high-performance liquid chromatography (HPLC), and polyethylene glycol (PEG) precipitation of plasma lipoproteins and immunoblotting analysis. Lp-PLA2 mass was determined by ELISA The ACS patients (18 males/5 females, mean age 57±9.2) had hsCRP levels of 32.6±60.4 mg/L (ACS visit1) vs. 1.9±1.3 mg/L (ACS visit2), reflecting systemic inflammation. Stable CAD hsCRP 1.3±1.3 mg/L and controls 0.6±0.2 mg/L did not differ significantly. HDL cholesterol levels were 1.02±0.24 mmol/L for ACS visit 1, 1.00±0.3 mmol/L for ACS visit2, and 1.11±0.29 mmol/L for stable CAD. Plasma Lp-PLA2 levels were significantly higher in ACS visit1 subjects than in the ACS visit2 (144.3±60.6 vs. 89.5±40.0 ng/mL, p&lt;0.0001). Interestingly, sCAD patients had slightly higher Lp-PLA2 levels that ACS visit 2 (p=0.003). The distribution of Lp-PLA2 differed according to the technique used. We found that only approximately 45% of Lp-PLA2 mass remained in the lipoprotein fraction (d&lt;1.21 g/L) after UTC, with the majority (43%) in the LDL fraction and only &lt;3% in the HDL fraction. The remainder (55% was found in the d&gt;1.21 g/L, suggesting that Lp-PLA2 is only loosely bound to lipoproteins, and the majority resides in LDL. Here, we show that subjects with an ACS have markedly increased Lp-PLA2 levels acutely and that these levels fall within 12 weeks. Surprisingly, Lp-PLA2 is only loosely bound to lipoproteins and may be displaced in inflammatory conditions. The increase in Lp-PLA2 in ACS may contribute to the generation of oxidized fatty acyls and lysophopsphlipids and potentially compound the local inflammatory reaction.

Promena paradigme za stabilnu koronarnu bolest u hronični koronarni sindromi - novine u vodiču Evropskog udruženja kardiologa iz 2019. godine

Background Immune checkpoint by programmed cell death (PD)-1 and its ligand (PD-L1) play crucial role in T cell tolerance toward vascular wall antigens. PD-L1 is widely expressed on a number of cells including immune cells and vascular endothelium. It was reported that increased expression of PD-L1 in dendritic cells implicates upregulated inflammation in atherosclerotic lesions that is associated with plaque instability. Although plaque rupture in coronary atherosclerosis is an important pathogenesis of acute coronary syndrome (ACS), the association between PD-L1 and ACS is still unknown. Purpose We hypothesize that circulating PD-L1 might be associated with ACS, reflecting endothelial damage and coronary plaque rupture. To elucidate this hypothesis, we compared serum levels of soluble PD-L1 (sPD-L1) in stable coronary artery disease (CAD) patients with those in ACS patients. Methods Serum levels of sPD-L1 were measured by using commercially available ELISA kit (Human PD-L1/B7-H1 DuoSet, R&amp;D Systems) in consecutive patients with CAD admitted to our University Hospital from February 2016 to March 2017. Patients with any malignant disease or severe inflammatory disease were excluded from this study. Serum levels of sPD-L1 and clinical backgrounds were compared between stable-CAD and ACS patients. Results In total, 269 patients with CAD were enrolled (28 cases [10.4 %] with ACS and 241 cases [89.6 %] with stable-CAD). PD-L1 had no correlation to C-reactive protein, cardiac troponin, and classical atherosclerotic risks such as age, body mass index, estimated glomerular filtration rate, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol, and hemoglobin A1c. Although age, sex, history of smoking, and the prevalences of hypertension, diabetes mellitus and dyslipidemia were comparable between both groups, the level of LDL-C was significantly higher in patients with ACS compared with those with stable-CAD (94.0 [77.0–112.0] mg/dL vs. 78.5 [65.0–97.0] mg/dL, P = 0.008). Also serum level of sPD-L1 was significantly increased in patients with ACS compared with those with stable-CAD (106.1 [60.9–157.7] pg/mL vs. 64.8 [30.9–102.5] pg/mL, P = 0.003). Univariate logistic regression analysis identified that serum levels of both sPD-L1 and LDL-C were independently associated with ACS. Moreover, multivariable logistic regression analysis with factors from univariate analysis identified that serum level of sPD-L1 was significantly and independently associated with ACS (odds ratio: 1.006, 95 % confidence interval: 1.001–1.012, P = 0.03). Conclusions This is the first study to elucidate that the increased serum levels of sPD-L1 was associated with ACS. This study suggests that sPD-L1 could be a risk marker and therapeutic target for ACS.

BackgroundThe main mechanism of acute coronary syndrome (ACS) is the rupture of atherosclerotic plaques. Matrix metalloproteinases (MMPs) play an important role in the rupture of the vulnerable plaques. MMP secretion is stimulated by CD147, one of the immunoglobulin families. Malondialdehyde is an important marker of oxidative damage, which is related to the atherosclerotic process. Superoxide dismutase normally prevents the oxidative process. This study was conducted to evaluate the association of ACS with CD147 gene expression, lipid peroxidation, and antioxidants in Egyptian population. The study included 124 people, 62 ACS patients and 62 healthy controls.ResultsCD147 gene expression in the ACS group was significantly increased compared to the control group (p < 0.001). The ACS was 9.71 ± 3.56-fold; the control group was 0.94 ± 0.19-fold. Also, the SOD activity in the ACS group was significantly increased when compared to the control group (t = 16.023, p < 0.001). There was a highly significant increase in the MDA level in ACS groups when compared to the control group (t = 35.536, p < 0.001). There was a highly significant increase in the creatine kinase-MB (CK-MB) and high sensitive troponin I levels in ACS groups when compared to the control group (p < 0.001).ConclusionThere is a highly significant positive correlation between CK-MB and CD147 in both control and ACS groups (p = <0.001**); also, there is highly significant positive correlation between high sensitive troponin I and CD 147 in both control and ACS groups (p = <0.001**), but we did not find significant correlation between SOD and CD147 or between MDA and CD 147 in both control and ACS groups.

Soluble lectin-like oxidized LDL receptor-1 (sLOX-1) as a valuable diagnostic marker for rupture of thin-cap fibroatheroma: Verification by optical coherence tomography

Part 7: The Era of Reperfusion

Acute coronary syndrome (ACS) represents a series of indications of sudden cardiac ischemia that involve a variety of causes, including acute myocardial infarction and unstable angina.1 ACS usually is associated with thrombus formation in the coronary artery or coronary artery vasospasm, resulting in myocardial ischemia. 2 Thrombus formation may involve platelet adhesion and degranulation on damaged or dysfunctional endothelium overlying the intact or ruptured atherosclerotic plaque, as well as microthrombi.3 Atherosclerotic plaque rupture represents a series of deleterious events linked to the breakdown of the fibrous cap. This process may occur as a result of the increased secretion of matrix metalloproteinases by lesion resident macrophages or enhanced apoptotic cell death within the fibrous cap. However, viable smooth muscle cells (SMCs) within the fibrous cap synthesize interstitial collagen fibers that enhance the structural integrity of the plaque and prevent its rupture.4

Ischemic heart disease includes a wide spectrum of conditions, ranging from silent ischemia and exertion-induced angina, through unstable angina, to acute MI. Unstable angina occupies the center of this spectrum, causing disability and risk greater than that of chronic stable angina but less than that of acute MI1 (Fig 1⇓). Although non–Q-wave MI for many years was considered prognostically similar to unstable angina, recent longitudinal studies indicate that it is similar to Q-wave infarction2 3 (Fig 2⇓). Figure 1. Cumulative 6-month mortality from ischemic heart disease. Diagnosis on admission to hospital (n=21 761; 1985 to 1992). From Duke Cardiovascular Database. Reproduced with permission from Reference 1. Figure 2. Top, Cumulative 1-year combined death or MI among patients with Q-wave and non–Q-wave MI treated with fibrinolysis. Reproduced with permission from Reference 2. Bottom, Risk of subsequent cardiac events in stable convalescing patients after first non–Q-wave and Q-wave MI. Reproduced with permission from Reference 3. The concept of unstable angina has emerged from observations of frequent symptoms preceding acute MI, followed by prospective documentation that unstable symptoms frequently culminated in acute MI. The syndrome was rapidly accepted as a well-defined clinical entity as specific clinical manifestations, pathophysiological mechanisms, laboratory findings, and treatment became better characterized. Unstable angina is currently one of the leading causes of hospital admission for CAD, and non–Q-wave MI accounts for >30% of admissions for acute MI.1 4 Yet, the diagnosis of unstable angina remains clinical, based on symptom recognition. The physician caring for patients with unstable angina is in a privileged position of recognizing rapidly evolving CAD and being able to intervene to prevent irreversible left ventricular damage and progression of CAD. Unstable angina is classically described as a heterogeneous disease, referring to a wide spectrum of clinical manifestations from stable angina to MI, of disease …