Virtual Hemodynamic Assessment of Coronary Lesions: The Advent of Functional Angiography and Coronary Imaging.

The fractional flow reserve (FFR) is well recognized as a gold standard measure for the estimation of functional coronary stenosis. Technological progressions in image processing have empowered the reconstruction of three-dimensional models of the coronary arteries via both non-invasive and invasive imaging modalities. The application of computational fluid dynamics (CFD) techniques to coronary 3D anatomical models allows the virtual evaluation of the hemodynamic significance of a coronary lesion with high diagnostic accuracy. METHODS: Search of the bibliographic database for articles published from 2011 to 2023 using the following search terms: invasive FFR and non-invasive FFR. Pooled analysis of the sensitivity and specificity, with the corresponding confidence intervals from 32% to 94%. In addition, the summary processing times were determined. RESULTS: In total, 24 studies published between 2011 and 2023 were included, with a total of 13,591 patients and 3345 vessels. The diagnostic accuracy of the invasive and non-invasive techniques at the per-patient level was 89% (95% CI, 85-92%) and 76% (95% CI, 61-80%), respectively, while on the per-vessel basis, it was 92% (95% CI, 82-88%) and 81% (95% CI, 75-87%), respectively. CONCLUSION: These opportunities providing hemodynamic information based on anatomy have given rise to a new era of functional angiography and coronary imaging. However, further validations are needed to overcome several scientific and computational challenges before these methods are applied in everyday clinical practice.

Spontaneous Coronary Artery Dissection and COVID-19: A Review of the Literature.

SARS-CoV-2 is responsible for the global coronavirus disease 2019 (COVID-19) pandemic. While the cardiovascular effects of COVID-19 have been thoroughly described, there are limited published studies in the literature establishing a connection between spontaneous coronary artery dissection (SCAD) and COVID-19. Cardiovascular manifestations include, among others, myocarditis, acute myocardial infraction, and thrombosis. In general, SCAD is an uncommon and underdiagnosed cause of acute myocardial infarction (AMI), particularly in younger women and in patients with underlying fibromuscular dysplasia (FMD). Many patients with SCAD often report significant emotional stress, especially in relation with job loss, during the week preceding their cardiac event. Moreover, the COVID-19 pandemic has led to societal stress and increased unemployment, factors that have been associated with cardiovascular morbidity. SCAD emerges as a rare manifestation of coronary artery disease, which a few recent case reports link to COVID-19. The aim of this article is to summarize the relevant data on the pathophysiology of COVID-19 and SCAD along with a review of the reported cases on acute coronary syndrome (ACS) following SARS-CoV2 infection and, thus, to provide insights about the relationship between COVID-19 and SCAD.

Absolute zero-contrast percutaneous coronary interventions: An intravascular ultrasound-guided case series and literature review.

PURPOSE: Contrast media (CM)-associated adverse effects including mainly acute kidney injury and hypersensitivity reactions still remain a significant treatment burden to vulnerable patients requiring percutaneous coronary intervention (PCI). The complete omission of CM administration accompanied by intravascular ultrasound (IVUS) guidance may offer an appropriate revascularization treatment. METHODS: We hereby present a case series of four patients with challenging coronary lesions and relative/absolute contraindications to CM use [(hypersensitivity reaction owning to CM, history of contrast-induced acute kidney injury, solitary kidney, or advanced chronic kidney disease (CKD)] who underwent absolute zero-contrast IVUS-guided PCI following a predetermined protocol. RESULTS: The initial diagnostic angiography was reviewed for landmark identification, and multiple guidewires created a metallic road map providing additional landmarks and protected side branches. IVUS imaging was performed to determine lesion length, reference segments and landing zones, assess stent expansion/apposition and identify major complications. All procedures were successfully completed without any CM administration, renal function deterioration, pericardial effusion, or stent edge dissection. CONCLUSIONS: We demonstrated the feasibility of absolute zero-contrast IVUS-guided PCI in patients with complex coronary lesions susceptible to CM-associated adverse effects. Since the safety of this strategy is well-documented in patients with CKD and challenging lesions morphology even in acute settings, evidence-based validation of this approach is capable of changing the otherwise conservative treatment of vulnerable patients where even minimum doses of CM may have detrimental effects. SUMMARY FOR THE ANNOTATED TABLE OF CONTENTS: Patients with vulnerable renal function as well as former hypersensitivity reaction to contrast media encounter a significant treatment burden regarding coronary artery disease. Zero-contrast IVUS-guided strategy based on a predetermined protocol provides a feasible alternative approach in patients susceptible to contrast media-associated adverse effects even in the presence of complex coronary lesions.

Role of FGF21 and Leptin for the Diagnosis of Metabolic Health in Children with and without Obesity.

Obesity and unfavorable metabolic profiles increase the risk for cardiovascular complications in adults. Although it is important to distinguish different metabolic health states at an early stage, there are limited data on the related value of biomarkers in childhood. We aimed to identify biomarkers for the detection of different metabolic health states in children with and without obesity. The serum levels of metabolic regulators (fibroblast growth factor 21 [FGF21], leptin, adiponectin and insulin-like growth factor binding protein 1) and vascular indices (flow-mediated dilation [FMD] and carotid intima-media thickness) were assessed in 78 children. Differences between the metabolically healthy and unhealthy state within children with normal weight (MHN vs. MUN), and within children with overweight/obesity (MHO vs. MUO) were investigated; the discriminatory power of the biomarkers was studied. Both MUN and MUO groups expressed altered lipid and glucose homeostasis compared to their healthy counterparts. The metabolic unhealthy state in children with normal weight was linked to higher FGF21 levels which had good discriminatory ability (area under the curve [AUC]: 0.71, 95% CI: 0.54-0.88; p = 0.044). In overweight/obese children, leptin was increased in the metabolically unhealthy subgroup (AUC: 0.81, 95% CI: 0.68-0.95; p = 0.01). There was a decrease in FMD indicating worse endothelial function in overweight/obese children versus those with normal weight. Distinct states of metabolic health exist in both children with normal weight and overweight/obese children. FGF21 and leptin may help to identify the metabolic unhealthy state in children with normal weight and in overweight/obese children, respectively, early in life.

Preventing and Managing Radial Artery Occlusion following Transradial Procedures: Strategies and Considerations.

Τransradial artery access has recently gained widespread acceptance as the preferred approach for coronary angiography and interventions, due to its lower incidence of bleeding and vascular complications compared to transfemoral access. However, thrombotic occlusion of the radial artery has emerged as the most common complication of this method, impeding its use in future interventions, and in the creation of arteriovenous fistulae for hemodialysis patients, or as a graft for coronary artery bypasses grafting. In this comprehensive review, we delve into the anatomy of the radial artery, the pathophysiology and diagnosis of radial artery occlusion, the identification of potential risk factors and, finally, prevention and treatment strategies. We acknowledge that distal transradial access provides an effective alternative for coronary angiography and catheterizations, with a reduced incidence of radial artery occlusion.

The role of endothelial shear stress, shear stress gradient, and plaque topography in plaque erosion.

BACKGROUND AND AIMS: Plaque erosion is a common underlying cause of acute coronary syndromes. The role of endothelial shear stress (ESS) and endothelial shear stress gradient (ESSG) in plaque erosion remains unknown. We aimed to determine the role of ESS metrics and maximum plaque slope steepness in plaques with erosion versus stable plaques. METHODS: This analysis included 46 patients/plaques from TOTAL and COMPLETE trials and Brigham and Women's Hospital's database who underwent angiography and OCT. Plaques were divided into those with erosion (n = 24) and matched stable coronary plaques (n = 22). Angiographic views were used to generate a 3-D arterial reconstruction, with centerlines merged from angiography and OCT pullback. Local ESS metrics were assessed by computational fluid dynamics. Among plaque erosions, the up- and down-slope (Δ lumen area/frame) was calculated for each culprit plaque. RESULTS: Compared with stable plaque controls, plaques with an erosion were associated with higher max ESS (8.3 ± 4.8 vs. 5.0 ± 1.9 Pa, p = 0.02) and max ESSG any direction (9.2 ± 7.5 vs. 4.3 ± 3.11 Pa/mm, p = 0.005). Proximal erosion was associated with a steeper plaque upslope while distal erosion with a steeper plaque downslope. Max ESS and Max ESSG any direction were independent factors in the development of plaque erosion (OR 1.32, 95%CI 1.06-1.65, p = 0.014; OR 1.22, 95% CI 1.03-1.45, p = 0.009, respectively). CONCLUSIONS: In plaques with similar luminal stenosis, plaque erosion was strongly associated with higher ESS, ESS gradients, and plaque slope as compared with stable plaques. These data support that ESS and slope metrics play a key role in the development of plaque erosion and may help prognosticate individual plaques at risk for future erosion.

Current Toolset in Predicting Acute Coronary Thrombotic Events: The "Vulnerable Plaque" in a "Vulnerable Patient" Concept.

Despite major advances in pharmacotherapy and interventional procedures, coronary artery disease (CAD) remains a principal cause of morbidity and mortality worldwide. Invasive coronary imaging along with the computation of hemodynamic forces, primarily endothelial shear stress and plaque structural stress, have enabled a comprehensive identification of atherosclerotic plaque components, providing a unique insight into the understanding of plaque vulnerability and progression, which may help guide patient treatment. However, the invasive-only approach to CAD has failed to show high predictive value. Meanwhile, it is becoming increasingly evident that along with the "vulnerable plaque", the presence of a "vulnerable patient" state is also necessary to precipitate an acute coronary thrombotic event. Non-invasive imaging techniques have also evolved, providing new opportunities for the identification of high-risk plaques, the study of atherosclerosis in asymptomatic individuals, and general population screening. Additionally, risk stratification scores, circulating biomarkers, immunology, and genetics also complete the armamentarium of a broader "vulnerable plaque and patient" concept approach. In the current review article, the invasive and non-invasive modalities used for the detection of high-risk plaques in patients with CAD are summarized and critically appraised. The challenges of the vulnerable plaque concept are also discussed, highlighting the need to shift towards a more interdisciplinary approach that can identify the "vulnerable plaque" in a "vulnerable patient".

Cerebro-/Cardiovascular Collateral Damage During the COVID-19 Pandemic: Fact or Fiction?

Numerous observational studies have identified a decline in cerebro-/cardiovascular (CV) admissions during the initial phase of the COVID-19 pandemic. Recent studies and meta-analyses indicated that the overall decrease was smaller than that found in initial studies during the first months of 2020. Two years later we still do not have clear evidence about the potential causes and impacts of the reduction of CV hospitalizations during the COVID-19 pandemic. It has becoming increasingly evident that collateral damage (i.e., incidental damage to the public and patients) from the COVID-19 outbreak is the main underlying cause that at least somewhat reflects the effects of imposed measures such as social distancing and self-isolation. However, a smaller true decline in CV events in the community due to a lack of triggers associated with such acute syndromes cannot be excluded. There is currently indirect epidemiological evidence about the immediate impact that the collateral damage had on excess mortality, but possible late consequences including a rebound increase in CV events are yet to be observed. In the present narrative review, we present the reporting milestones in the literature of the rates of CV admissions and collateral damage during the last 2 years, and discuss all possible factors contributing to the decline in CV hospitalizations during the COVID-19 pandemic. Healthcare systems need to be prepared so that they can cope with the increased hospitalization rates for CV events in the near future.

Body Mass Index Is Independently Associated with the Presence of Ischemia in Myocardial Perfusion Imaging.

Background and Objectives: Obesity has been linked to various cardiovascular risk factors, increased incidence of coronary artery disease, and myocardial perfusion defects. The aim of this study was to investigate if body mass index (BMI) and waist circumference (WC) were associated with myocardial perfusion defects. Materials and Methods: A total of 308 consecutive patients who had myocardial perfusion imaging (MPI) with single photon emission computed tomography (SPECT) and a complete medical record on file were studied retrospectively. Results: The median age was 69 (61−76) years, the BMI was 27.6 (24.4−30.7) kg/m2, and the WC was 110 (102−118) cm. Of the 308 patients, 239 patients (77.6%) had myocardial ischemia. A positive test for ischemia was more frequent in men compared to women (72 vs. 28%, p < 0.001). Within the male group, BMI and WC were not significantly different between the ischemia and non-ischemia groups. In contrast, within the female group, both BMI (30.2 vs. 27.1 kg/m2, p = 0.002) and WC (112 vs. 105.5 cm, p = 0.020) were significantly higher in the ischemia group. Multivariable logistic regression showed that male sex and BMI were the only two independent predictors of ischemia in our patient population. Conclusions: This study showed that BMI was an independent predictor of ischemia in our patient population.

Optical coherence tomography in coronary atherosclerosis assessment and intervention.

Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application.

Three-vessel spontaneous coronary artery dissection in a patient with hyperhomocysteinemia.

Increased homocysteine has been related to the occurrence of dissections in the coronary circulation, aorta, and cervical arteries. Spontaneous coronary artery dissection (SCAD) is a relatively rare phenomenon, and data on the long-term follow-up of patients with SCAD are extremely limited. Herein, we describe a case of a young male patient with 3-vessel SCAD (presence of radiolucent linear defects indicating the presence of dissections in all three major coronary arteries) who was found to have hyperhomocysteinemia and a concurrent methylenetetrahydrofolate reductase prothrombotic mutation. Despite the presence of multi-vessel SCAD, the patient had clinically stable coronary artery disease for a long period. .

Sex-related differences in plaque characteristics and endothelial shear stress related plaque-progression in human coronary arteries.

BACKGROUND AND AIMS: Clinical atherosclerosis manifestations are different in women compared to men. Since endothelial shear stress (ESS) is known to play a critical role in coronary atherosclerosis development, we investigated differences in anatomical characteristics and endothelial shear stress (ESS)-related plaque growth in human coronary arteries in men compared to women. METHODS: 1183 coronary arteries (male/female: 944/239) from the PREDICTION study were studied for differences in artery/plaque and ESS characteristics, and ESS-related plaque progression (6-10 months follow-up) among men and women and after stratification for age. All characteristics were derived from IVUS-based vascular profiling and reported per 3 mm-segments (13,030 3-mm-segments (male/female: 10,465/2,565)). RESULTS: Coronary arteries and plaques were significantly smaller in females compared to males; but no important differences were observed in plaque burden, ESS and rate of plaque progression. Change in plaque burden was inversely related to ESS (p<0.001) with no difference between women versus men (ß: -0.62 ± 0.13 vs -0.68 ± 0.05, p=0.62). However, stratification for age demonstrated that ESS-related plaque growth was more marked in young women compared to men (<55 years, ß: -2.02 ± 0.61 vs -0.33 ± 0.10, p=0.007), reducing in magnitude over the age-categories up till 75 years. CONCLUSIONS: Coronary artery and plaque size are smaller in women compared to men, but ESS and ESS- related plaque progression were similar. Sex-related differences in ESS-related plaque growth were evident after stratification for age. These observations suggest that although the fundamental processes of atherosclerosis progression are similar in men versus women, plaque progression may be influenced by age within gender.

Elderly patients with non-cardiac admissions and elevated high-sensitivity troponin: the prognostic value of renal function.

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) levels are frequently elevated in elderly patients presenting to the emergency department for non-cardiac events. However, most studies on the role of elevated hs-cTn in elderly populations have investigated the prognostic value of hs-cTn in patients with a specific diagnosis or have assessed the relationship between hs-cTn and comorbidities. AIM: To investigate the in-hospital prognosis of consecutive elderly patients admitted to the Internal Medicine Department with acute non-cardiac events and increased hs-cTnI levels. METHODS: In this retrospective study, we selected patients who were aged ≥ 65 years and admitted to the Internal Medicine Department of our hospital between January 2019 and December 2019 for non-cardiac reasons. Eligible patients were those who had hs-cTnI concentrations ≥ 100 ng/L. We investigated the independent predictors of in-hospital mortality by multivariable logistic regression analysis. RESULTS: One hundred and forty-six patients (59% female) were selected with an age range from 65 to 100 (mean ± SD: 85.4 ± 7.61) years. The median hs-cTnI value was 284.2 ng/L. For 72 (49%) patients the diagnosis of hospitalization was an infectious disease. The overall in-hospital mortality was 32% (47 patients). Individuals who died did not have higher hs-cTnI levels compared with those who were discharged alive (median: 314.8 vs 282.5 ng/L; P = 0.565). There was no difference in mortality in patients with infectious vs non-infectious disease (29% vs 35%). Multivariable analysis showed that age (OR 1.062 per 1 year increase, 95%CI: 1.000-1.127; P = 0.048) and creatinine levels (OR 2.065 per 1 mg/dL increase, 95%CI: 1.383-3.085; P < 0.001) were the only independent predictors of death. Mortality was 49% in patients with eGFR < 30 mL/min/1.73 m2. CONCLUSION: Myocardial injury is a malignant condition in elderly patients admitted to the hospital for non-cardiac reasons. The presence of severe renal impairment is a marker of extremely high in-hospital mortality.

Exercise-mediated adaptations in vascular function and structure: Beneficial effects in coronary artery disease.

Exercise exerts direct effects on the vasculature via the impact of hemodynamic forces on the endothelium, thereby leading to functional and structural adaptations that lower cardiovascular risk. The patterns of blood flow and endothelial shear stress during exercise lead to atheroprotective hemodynamic stimuli on the endothelium and contribute to adaptations in vascular function and structure. The structural adaptations observed in arterial lumen dimensions after prolonged exercise supplant the need for acute functional vasodilatation in case of an increase in endothelial shear stress due to repeated exercise bouts. In contrast, wall thickness is affected by rather systemic factors, such as transmural pressure modulated during exercise by generalized changes in blood pressure. Several mechanisms have been proposed to explain the exercise-induced benefits in patients with coronary artery disease (CAD). They include decreased progression of coronary plaques in CAD, recruitment of collaterals, enhanced blood rheological properties, improvement of vascular smooth muscle cell and endothelial function, and coronary blood flow. This review describes how exercise via alterations in hemodynamic factors influences vascular function and structure which contributes to cardiovascular risk reduction, and highlights which mechanisms are involved in the positive effects of exercise on CAD.

SmartFFR, a New Functional Index of Coronary Stenosis: Comparison With Invasive FFR Data.

Aims: In this study, we evaluate the efficacy of SmartFFR, a new functional index of coronary stenosis severity compared with gold standard invasive measurement of fractional flow reserve (FFR). We also assess the influence of the type of simulation employed on smartFFR (i.e. Fluid Structure Interaction vs. rigid wall assumption). Methods and Results: In a dataset of 167 patients undergoing either computed tomography coronary angiography (CTCA) and invasive coronary angiography or only invasive coronary angiography (ICA), as well as invasive FFR measurement, SmartFFR was computed after the 3D reconstruction of the vessels of interest and the subsequent blood flow simulations. 202 vessels were analyzed with a mean total computational time of seven minutes. SmartFFR was used to process all models reconstructed by either method. The mean FFR value of the examined dataset was 0.846 ± 0.089 with 95% CI for the mean of 0.833-0.858, whereas the mean SmartFFR value was 0.853 ± 0.095 with 95% CI for the mean of 0.84-0.866. SmartFFR was significantly correlated with invasive FFR values (RCCTA = 0.86, p CCTA < 0.0001, RICA = 0.84, p ICA < 0.0001, R overall = 0.833, p overall < 0.0001), showing good agreement as depicted by the Bland-Altman method of analysis. The optimal SmartFFR threshold to diagnose ischemia was ≤0.83 for the overall dataset, ≤0.83 for the CTCA-derived dataset and ≤0.81 for the ICA-derived dataset, as defined by a ROC analysis (AUCoverall = 0.956, p < 0.001, AUCICA = 0.975, p < 0.001, AUCCCTA = 0.952, p < 0.001). Conclusion: SmartFFR is a fast and accurate on-site index of hemodynamic significance of coronary stenosis both at single coronary segment and at two or more branches level simultaneously, which can be applied to all CTCA or ICA sequences of acceptable quality.

Association of fibroblast growth factor 21 with metabolic syndrome and endothelial function in children: a prospective cross-sectional study on novel biomarkers.

PURPOSE: Metabolic and cardiovascular disease prevention starting in childhood is critical for reducing morbidity later in life. In the present study, the association of novel biomarkers with metabolic syndrome (MS) and vascular function/structure indices of early atherosclerosis in children was investigated. METHODS: This was a prospective study of 78 children (8-16 years of age) grouped based on the presence or absence of MS. The serum biomarkers investigated included fibroblast growth factor 21 (FGF21), leptin, adiponectin, and insulinlike growth factor binding protein-1 (IGFBP1). Endothelial function and carotid atherosclerosis were assessed based on brachial artery flow-mediated dilation (FMD) and carotid intima-media thickness, respectively. RESULTS: Children with MS (n=12) had higher levels of FGF21 (median [interquartile range]: 128 [76-189] pg/mL vs. 60 [20-98] pg/mL, P=0.003) and leptin (18.1 [11-34.8] pg/mL vs. 7.5 [1.9-16.5] ng/mL, P=0.003), and lower levels of IGFBP1 (1.5 [1.2-2.1] ng/mL vs. 2.3 [1.5-6] ng/mL, P=0.028) compared with children without MS. FMD inversely correlated with FGF21 (Spearman rho= -0.24, P=0.035) and leptin (rho= -0.24, P=0.002) in all children. The best cutoff value of FGF21 levels for MS diagnosis was above 121.3 pg/mL (sensitivity/specificity, 58/86%). Only FGF21 was significantly associated with the presence of MS after adjustment for body mass index, age, and sex (odds ratio per 10 pg/mL increase: 1.10 [95% confidence interval, 1.01-1.22]; P=0.043). CONCLUSION: Increased FGF21 levels were associated with the presence of MS and worse endothelial function in children. Larger studies are needed to evaluate the potential value of FGF21 as a biomarker that could predict future metabolic/cardiovascular disease at an early stage.

Spatial relationships among hemodynamic, anatomic, and biochemical plaque characteristics in patients with coronary artery disease.

BACKGROUND AND AIMS: We aimed to characterize the spatial proximity of plaque destabilizing features local endothelial shear stress (ESS), minimal luminal area (MLA), plaque burden (PB), and near-infrared spectroscopy (NIRS) lipid signal in high- vs. low-risk plaques. METHODS: Coronary arteries imaged with angiography and NIRS-intravascular ultrasound (IVUS) underwent 3D reconstruction and computational fluid dynamics calculations of local ESS. ESS, PB, MLA, and lipid core burden index (LCBI), for each 3-mm arterial segment were obtained in arteries with large lipid-rich plaque (LRP) vs. arteries with smaller LRP. The locations of the MLA, minimum ESS (minESS), maximum ESS (maxESS), maximum PB (maxPB), and maximum LCBI in a 4-mm segment (maxLCBI4mm) were determined along the length of each plaque. RESULTS: The spatial distributions of minESS, maxESS, maxPB, and maxLCBI4mm, in reference to the MLA, were significantly heterogeneous within and between each variable. The location of maxLCBI4mm was spatially discordant from sites of the MLA (p<0.0001), minESS (p = 0.003), and maxESS (p = 0.003) in arteries with large LRP (maxLCBI4mm ≥ 400) and non-large LRP. Large LRP arteries had higher maxESS (9.31 ± 4.78 vs. 6.32 ± 5.54 Pa; p = 0.023), lower minESS (0.41 ± 0.16 vs. 0.61 ± 0.26 Pa; p = 0.007), smaller MLA (3.54 ± 1.22 vs. 5.14 ± 2.65 mm2; p = 0.002), and larger maxPB (70.64 ± 9.95% vs. 56.70 ± 13.34%, p<0.001) compared with non-large LRP arteries. CONCLUSIONS: There is significant spatial heterogeneity of destabilizing plaque features along the course of both large and non-large LRPs. Large LRPs exhibit significantly more abnormal destabilizing plaque features than non-large LRPs. Prospective, longitudinal studies are required to determine which patterns of heterogeneous destabilizing features act synergistically to cause plaque destabilization.

"Missing" acute coronary syndrome hospitalizations during the COVID-19 era in Greece: Medical care avoidance combined with a true reduction in incidence?

BACKGROUND: Reports from countries severely hit by the COVID-19 pandemic suggest a decline in acute coronary syndrome (ACS)-related hospitalizations. The generalizability of this observation on ACS admissions and possible related causes in countries with low COVID-19 incidence are not known. HYPOTHESIS: ACS admissions were reduced in a country spared by COVID-19. METHODS: We conducted a nationwide study on the incidence rates of ACS-related admissions during a 6-week period of the COVID-19 outbreak and the corresponding control period in 2019 in Greece, a country with strict social measures, low COVID-19 incidence, and no excess in mortality. RESULTS: ACS admissions in the COVID-19 (n = 771) compared with the control (n = 1077) period were reduced overall (incidence rate ratio [IRR]: 0.72, P < .001) and for each ACS type (ST-segment elevation myocardial infarction [STEMI]: IRR: 0.76, P = .001; non-STEMI: IRR: 0.74, P < .001; and unstable angina [UA]: IRR: 0.63, P = .002). The decrease in STEMI admissions was stable throughout the COVID-19 period (temporal correlation; R2 = 0.11, P = .53), whereas there was a gradual decline in non-STEMI/UA admissions (R2 = 0.75, P = .026) following the progressively stricter social measures. During the COVID-19 period, patients admitted with ACS presented more frequently with left ventricular systolic impairment (22.2 vs 15.5% control period; P < .001). CONCLUSIONS: We observed a reduction in ACS hospitalizations during the COVID-19 outbreak in a country with strict social measures, low community transmission, and no excess in mortality. Medical care avoidance behavior is an important factor for these observations, while a true reduction of the ACS incidence due to self-isolation/quarantining may have also played a role.