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Introduction Atherosclerotic plaque healing is a dynamic process that promotes plaque repair after destabilization. Previous studies showed that healed plaques are more common in patients with chronic coronary syndrome than in those with acute coronary syndrome, suggesting that they might be a marker of clinical stability. The mechanisms underlying plaque healing are not completely understood. The aim of the present study was to evaluate sex-based differences in plaque phenotype and healing of non-culprit coronary lesions by optical coherence tomography. Methods In this observational, single-center cohort study, we enrolled patients from the OCT Registry of the Fondazione Policlinico A Gemelli IRCCS. A total of 205 patients with both acute coronary syndromes or chronic coronary syndromes undergoing coronary angiography and intravascular OCT imaging of non-culprit vessels were included in the analysis and divided into two groups according to gender. Results Of 205 patients, 153 were male (75%) and 52 (25%) female. Compared with male patients, female patients had lower prevalence of lipid-rich plaque (40.4% vs. 57.7%; p=0.030), plaque rupture (7.7% vs. 21.2%; p=0.028) and cholesterol crystal (13.5% vs. 29.5%; p=0.022). Mean lipid arc and calcium depht were significantly lower in female patients than in male ones (118.0° ± 79.9° vs. 135.5° ± 77.9°; p=0.011; and 52.7 µm ± 79.2 µm vs. 72.3 µm ± 93.5 µm; p=0.007) while fibrous cap tended to be thicker (108.2 µm ± 70.4 µm vs. 96.2 µm ± 72.9 µm; p=0.055). Healed plaques were significantly more frequent in female patients than in male patients (51.9% vs 34.6%; p = 0.027). The prevalence of fibrous plaque, thrombi, neovascularization, diffuse calcifications and spotty calcification was not different between the two groups. Conclusion Females have a distinct atherosclerotic phenotype and healing capacity compared with male patients, including lower prevalence of lipid-rich plaque, cholesterol crystals and plaque ruptures and higher prevalence of healed plaques in non-culprit coronary lesions.

Rational The occurrence of stent thrombosis (ST) is a rare event, but it remains one of the most catastrophic complications following percutaneous coronary intervention (PCI). Coronary angiography has limited value in differentiating the causative factors responsible for ST. Technical resolutions We report a case of a 78-year-old male, hypertensive and dyslipidemic who underwent PCI with stenting of the mid left anterior descending artery (LAD) due to chronic coronary syndrome (CCD) two years before. He was admitted to our emergency department for syncopal episode occurred at rest followed by chest pain radiating to the left arm and to the neck. At the time of admission, his electrocardiogram showed diffuse ST-segment elevation in V2-V6 and DI-aVL, therefore patient was urgently sent to the cath lab. Coronary angiography showed LAD occlusion at the proximal edge of the previously implanted stent with TIMI flow grade 0 and TIMI thrombus grade 5. Multiple thrombus aspiration passes were performed with distal flow restoration, followed by intracoronary abciximab administration. After additional thrombus aspiration passes, ST-segment resolution was observed and chest pain improved significantly. OCT imaging of mid-to-proximal LAD was then performed to better characterize the cause of thrombosis. OCT revealed in stent-thrombosis with mixed thrombus (6 mm length, arc >270°) associated with major stent malapposition (maximum malapposition distance: 1.3 mm) at the proximal edge of the previous implanted stent, without evidence of neoatherosclerosis and/or residual disease with unstable features at the stent edges. Additional thrombus aspiration was performed, further reducing the thrombotic burden. As te patient was hemodynamically stable and asymptomatic, with TIMI flow grade 3 at coronary angiography, we decided to start dual antiplatelet therapy (ASA+ticagrelor) plus continuous heparin i.v. infusion, and to defer PCI, planning a control coronary angiography after 72 hours. After 72 hours, OCT revealed almost complete thrombus resolution, and guided PCI with a 4.0/8 mm everolimus-eluting stent in overlap with the previously implanted stent, postdilated with a 4.5 semi-compliant balloon at 18 atm. Revascularization was completed with an OCT-guided PCI of the proximal left circumflex during the same procedure. Clinical implications Our case demonstrates the utility of OCT in determining thrombus burden and assessing the causes of late stent failure, guiding PCI. In this case, OCT was useful as diagnostic tool to identify the mechanism underlying the very-late ST, and as guidance for treatment. It enabled to exclude neoatherosclerosis and/or unstable plaques at stent edges, leaving us more confident to defer PCI after 72 h of antithrombotic therapy. Perspectives The occurrence of ST is rare, but it remains one of the most catastrophic complications following PCI. Coronary angiography has limited value in differentiating the causative factors responsible for ST, while OCT allows to detect and characterize the causes of stent thrombosis (i.e., evaluate thrombus burden, presence of neoatherosclerosis, stent malapposition/underxpansion, uncovred stent struts, significant disease and/or unstable plaques at the stent edges, etc.). A better understanding of the pathophysiological mechanism underlying ST is an important clinical need. The increasing availability of high-resolution intravascular imaging techniques such as OCT provides new opportunities for tailoring treatment strategy and guiding PCI.

Introduction Pathological studies have shown that many atherosclerotic plaques destabilize without resulting in a clinical manifestation. Recent in vivo studies showed that healed plaques are more common in patients with chronic coronary syndrome (CCS) than in those with acute coronary syndrome (ACS), suggesting that they might be a marker of clinical stability. The aim of the present study was to evaluate the clinical impact of healed coronary plaques detected by optical coherence tomography (OCT) imaging. Methods A total of 208 patients with CCS or ACS who underwent OCT imaging of non-target/non-culprit vessels were enrolled. Only non-culprit segments were analyzed. Patients were divided into two groups according to the presence or absence of healed plaques detected by OCT. The incidence of major adverse cardiac events (MACE) at follow-up was assessed, defined as the composite of cardiac death, non-fatal myocardial infarction, and target vessel revascularization (TVR). Results Healed coronary plaques were observed in 39.7% of patients, and the prevalence was higher in those presenting with chronic coronary syndrome. Median follow-up time was 4 years, and was not different between the two groups. Patients with healed plaques had a significantly lower incidence of MACE at follow-up (13.6% vs 22%, p=0.019), mainly driven by a lower rate of non-fatal myocardial infarctions (4.9% vs 10.2%, p=0.05). The incidence of cardiac death and TVR was not significantly different between the two groups (1.2% vs. 3.1%, p=0.288; and 13.6% vs. 15.0%, p= 0.187, respectively). At multivariate Cox regression analysis, the presence of plaque disruption was an independent predictor of MACE (odds ratio [OR] 3.33, 95% confidence interval [CI] 1.39-7.98, p=0.007), while the presence of healed plaque was an independent protective factor (OR 0.44, 95% CI 0.22-0.89, p=0.022). Conclusions Healed coronary plaques detected by OCT imaging are associated with a favorable clinical outcome at long-term follow-up.

Background Coronavirus disease 2019 (COVID-19) is a pandemic disease that is causing a public health emergency. Characteristics and clinical significance of myocardial injury remain unclear. Methods This retrospective single-center study analyzed 189 patients who received a COVID-19 diagnosis out of all 758 subjects with a high sensitive troponin I (Hs-TnI) measurement within the first 24 h of admission at the Policlinico A.Gemelli (Rome, Italy) between February 20th 2020 to April 09th 2020. Results The prevalence of myocardial injury in our COVID-19 population is of 16%. The patients with cardiac injury were older, had a greater number of cardiovascular comorbidities and higher values of acute phase and inflammatory markers and leucocytes. They required more frequently hospitalization in Intensive Care Unit (10 [32.3%] vs 18 [11.4%]; p = .003) and the mortality rate was significantly higher (17 [54.8%] vs. 15 [9.5%], p Conclusions In this study we demonstrate that hs-Tn can significantly predict disease severity, intubation need and in-hospital death. Therefore, it may be reasonable to use Hs-Tn as a clinical tool in COVID-19 patients in order to triage them into different risk groups and can play a pivotal role in the detection of subjects at high risk of cardiac impairment during both the early and recovery stage.

A 64-year-old man, prior smoker, with a history of paroxysmal atrial fibrillation was referred to our hospital due to worsening dyspnoea, progressively worsening angina, and a positive stress EKG testing. Coronary angiography (CAG) showed an angiographically intermediate stenosis of the mid left anterior descending (LAD) artery and a focal, complex lesion of the distal right coronary artery (RCA) (Figure 1A and B, red arrow). Treatment of the LAD stenosis was deferred based on a negative fractional flow reserve value (i.e. 0.85). Optical coherence tomography (OCT) imaging (ILUMIEN OPTIS, Abbott Vascular, Santa Clara, CA) was performed to better characterize the RCA lesion, which disclosed a ruptured thin-cap fibroatheroma (TCFA) with a large ‘empty’ cavity (Figure 1C–G, red arrows) and overlying ‘layered’ tissue (Figure 1H, white arrowheads). Based on these OCT findings, suggestive of initial plaque healing, and on a large residual lumen dimension (i.e. minimum lumen area, MLA, at the rupture site: 7.7 mm2), this lesion was not treated with percutaneous coronary intervention. The patient was discharged on aspirin, edoxaban, metoprolol, rosuvastatin, and ezetimibe, and remained clinically stable for more than 1 year. Due to angina recurrence, a new CAG was performed 18 months after the first admission, revealing a progression of the mid LAD stenosis that was treated with a 2.5/28 mm drug-eluting stent, and an improvement of the RCA lesion angiographic appearance (smooth contour) (Figure 1A′–B′). RCA OCT imaging was repeated demonstrating a complete healing of the large rupture cavity with all the hallmarks of the reparative process (Figure 1C′–H′): (1) re-established fibrous cap integrity and smooth vessel lumen profile; (2) thickening of the fibrous cap and reduction of lipid burden (i.e., transformation of TCFA into thick-cap fibroatheroma, ThCFA); (3) replacement of the ‘empty’ cavity with new ‘granulation tissue’; (4) initial calcification of the plaque; (5) heterogeneous signal-rich layers with distinct optical-signal intensity (layered, ‘onion-like’ pattern); and (6) mild lumen narrowing (MLA at the rupture site: 6.9 mm2).

Aims Atherosclerotic plaque healing is a dynamic process developing after plaque rupture or erosion, which aims to prevent lasting occlusive thrombus formation and to promote plaque repair. We hypothesized that diabetes mellitus, one of the major conventional cardiovascular risk factors, may influence the healing capacity after plaque destabilization. Methods and results In this single-centre observational cohort study, patients with acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) who underwent optical coherence tomography (OCT) imaging at Fondazione Policlinico A. Gemelli–IRCCS, Rome, were included. Patients were divided into two groups (i.e. diabetes vs. no diabetes), and stratified based on diabetes medications (i.e. insulin, vs. oral antidiabetic drugs). OCT analysis of non-culprit coronary segments was performed. 105 patients were included (44 diabetes, 61 no diabetes). Prevalence of HCPs was not significantly different between patients with and without diabetes (3.6% vs. 3.8%, P = 0.854). However, patients with diabetes on insulin showed a lower prevalence of HCPs both at patient-based (7.1% vs. 26.4%, P = 0.116) and at segment-based analysis (1.2% vs. 4.2%, P = 0.020). When comparing HbA1c levels based on the presence or absence of healed plaque at the non-culprit lesions, patients with healed plaque showed significantly lower levels of HbA1c compared to patients without healed plaques (43.5 ± 12.1% vs. 61.2 ± 10.4%, P Conclusions Patients with diabetes have a distinct coronary non-culprit plaque phenotype. Healing capacity may be impaired in patients with advanced diabetes on insulin therapy and in those with a suboptimal control of the disease. Further prospective, larger scale studies are warranted to confirm these findings.

Aims Due to its bidimensional nature, angiography is not always sufficient to accurately define coronary lesions, in particular when they are ambiguous or indeterminate. Intracoronary imaging, such as intravascular ultrasound or optical coherence tomography (OCT), is often useful in these cases to better characterize the ambiguous angiographic images, to identify the culprit lesion during acute coronary syndrome (ACS) and to guide percutaneous coronary intervention (PCI). Methods and results We report a case of a 61-year-old male with multiple cardiovascular risk factors and a previous ST-segment elevation myocardial infarction treated by PCI of the right coronary artery (RCA) about 7 years before, wo was admitted to our emergency department after acute onset chest pain. At the time of admission, his ECG was normal and cardiac troponin was below the upper reference limit of normality with positive molecular SARS-CoV-2 diagnostic test. Echocardiogram disclosed a mild left ventricular dysfunction with inferior wall hypokinesia. Coronary angiography showed a moderate in-stent restenosis at mid RCA and a hazy, undetermined image at the proximal edge of the previously implanted stent. Left coronary artery angiography showed only diffuse atherosclerotic disease without significant stenoses and a myocardial bridge at the mid tract of left anterior descending artery. OCT pullback of RCA to better characterize the undetermined lesions shown by angiography. OCT revealed significant neointima hyperplasia and a focal area of neoatherosclerosis with unstable features (fissure/microthrombi) at mid RCA. Severe stent strut malapposition embedded neointimal hyperplasia was observed at the proximal stent edge, resulting in ‘dual’ lumen appearance. The two lesions were treated with a single 3.5/48 mm everolimus-eluting stent (stent-in-stent), which was post-dilated with a 3.5/20 mm non-compliant balloon (18 atm) in the mid-to-distal segments, and 4.5/15 mm (16 atm) and 5.0/8 mm (14 atm) semi-compliant balloons in the proximal stent segment. Post-PCI OCT imaging confirmed good stent expansion and apposition. Our case demonstrates the utility of OCT in clarifying the aetiology of ambiguous angiographic lesions and as a guide for PCI. Indeed, the ‘hazy’ appearance on the angiograms corresponded to the major stent malapposition covered by neointima disclosed by OCT as a ‘dual-lumen’. Of note, OCT allowed to confirm the correct guidewire position in the ‘true’ lumen preventing a crush of the previously implanted stent. OCT was also useful as a diagnostic modality for the identification and characterization of the mechanism underlying the ACS (neoatherosclerosis instability). Conclusions Due to its unprecedented spatial resolution, OCT enables an ‘optical biopsy’ of the coronary artery wall and intrastent tissue. Therefore, OCT imaging should be considered when lesions are ambiguous or indetermined by coronary angiography to guide the diagnosis and treatments of ACS patients. OCT imaging is also useful to guide stenting and to optimize PCI result, and its impact on clinical outcome is under investigation in large randomized clinical trials.

Aims Spontaneous coronary artery dissection (SCAD) is a non-traumatic and non-iatrogenic separation of the coronary arterial walls, creating a false lumen. SCAD is an infrequent and often missed diagnosis especially in women presenting with acute coronary syndrome and in the majority of cases angiography alone could be insufficient for identification. Methods and results A 43-year-old woman presented to the Emergency Department of Fondazione Policlinico Universitario A. Gemelli IRCCS (Rome, Italy) for oppressive acute chest pain radiated to the right jaw, resolved spontaneously within a few minutes. Physical examination, including cardiovascular evaluation, was normal. High-sensitivity troponin was 152 ng/l and 250 ng/l in two serial determination (reference range, 0.0–37 ng/l). EKG showed sinus rhythm with no significant ST-segment alterations. Echocardiography revealed preserved biventricular systolic function with mild hypokinesia of the apical segments of the left ventricle. A diagnosis of NSTEMI was made based on clinical and laboratory parameters. Thus, urgent coronary angiography was performed, which demonstrated a single vessel disease with an eccentric, and angiographically complex stenosis of the proximal left anterior descending (LAD) artery with an image of plus compatible with a plaque ulceration. In order to define the extension of the disease and ostium involvement for a better procedural planning, OCT imaging was performed. Surprisingly, OCT showed a intramural haematoma extending from the ADA ostium to the proximal tract (approximately 22 mm) with ulceration in the body, minimal lumen area (MLA) 2.0 mm2 and evidence of normal trilaminar structure of the vessel both on downstream and upstream of the lesion. The angiographic features were compatible with type 2A SCAD. The therapeutic management was conservative with continuation of the double antiplatelet therapy and remote CT monitoring. Three days later, because of a new onset of chest pain and slight elevation of the ST segment on EKG, was performed a coronarographic control: the angiographic appearance of the lesion was substantially unchanged; OCT showed unmodified longitudinal extension of the lesion (about 22 mm) and relative increase in the endoluminal caliber compared to the previous examination (MLA 4.0 mm2).After 2 weeks, coronary CTA control was carried out, which documented the stability of the intramural hematoma in the proximal LAD, extended for 22 mm and with a maximum thickness of 2 mm, determining lumen narrowing of 40–45% The patient was discharged on medical therapy and no events occurred during the follow-up. Six month later, repeat CTA showed a complete resorption of the intramural haematoma. Conclusions In this case we highlight the utility of intravascular imaging, in particular OCT, in the evaluation of angiographic lesions of non-univocal interpretation and how its use can change the management and prognosis of ACS patients. Furthermore, the spontaneous resolution of the clinical and anatomical scenario through conservative treatment additionally confirms spontaneous healing as the natural history of SCAD and foreground the role of precise diagnosis (and intravascular imaging showed to improve it) for therapy shift and calibration.

Heart failure (HF) is a complex clinical syndrome with a huge social burden in terms of cost, morbidity, and mortality. Brain natriuretic peptide (BNP) appears to be the gold standard in supporting the daily clinical management of patients with HF. Novel biomarkers may supplement BNP to improve the understanding of this complex disease process and, possibly, to personalize care for the different phenotypes, in order to ameliorate prognosis. In this review, we will examine some of the most promising novel biomarkers in HF. Inflammation plays a pivotal role in the genesis and progression of HF and, therefore, several candidate molecules have been investigated in recent years for diagnosis, prognosis, and therapy monitoring. Noncoding RNAs are attractive as biomarkers and their potential clinical applications may be feasible in the era of personalized medicine. Given the complex pathophysiology of HF, it is reasonable to expect that the future of biomarkers lies in the application of precision medicine, through wider testing panels and “omics” technologies, to further improve HF care delivery.

Background and Sex and cognitive profile may be related to the laterality of motor symptoms in idiopathic Parkinson's disease. Introduction Parkinson's disease (PD) is well recognised as an inherently asymmetric disease with unilateral onset of motor symptoms. The laterality of motor symptoms may be linked to sex, clinical and demographic variables, and neuropsychological disorders. However, the available data are inconsistent. This study aimed to explore the potential association between the laterality of motor symptoms and clinical and demographic variables and deficits in specific cognitive domains. Material and methods We retrospectively recruited 97 participants with idiopathic PD without dementia; 60 presented motor symptoms on the left side and 37 on the right side. Both groups were comparable in terms of age, age at disease onset, disease duration, and severity of the neurological deficits according to the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. Results Participants with left-side motor symptoms scored lower on the Schwab and England Activities of Daily Living scale. Our sample included more men than women (67% vs. 33%). Both sexes were not equally represented in the 2 groups: there were significantly more men than women in the group of patients with left-side motor symptoms (77% vs. 23%), whereas the percentages of men and women in the group of patients with right-side motor symptoms were similar (51% vs. 49%). Both groups performed similarly in all neuropsychological tasks, but women, independently of laterality, performed better than men in the naming task. Conclusion We found a clear prevalence of men in the group of patients with left-side motor symptoms; this group also scored lower on the Schwab and England Scale. Female sex was predictive of better performance in the naming task. Sex should always be considered in disorders that cause asymmetric involvement of the brain, such as PD.

Introduction: Coronavirus disease 2019 (COVID-19) is a pandemic disease that has caused a public health emergency due to its high rapid spread, to the high mortality rate, and the high percentage of patients requiring hospitalization and intensive care . Information regarding the impact of cardiovascular complication on fatal outcome is scarce. Purpose: To compare the levels of hs-Tn between patients affected by SARS-CoV-2 admitted to our hospital in the period February 20-April 9, 2020 versus the general population COVID free. Furthermore, we studied the dependence of hs-Tn levels in SARS-CoV-2 patients on disease severity and on other epidemiological, clinical and laboratory parameters. Methods: This retrospective single-center study analyzed all patients in whom hs-TnI was determined at the Policlinico A.Gemelli (Rome, Italy) from 20 February 2020 to 09 April 2020. One hundred-seventy of these patients received SARS-CoV-2 diagnosis. Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with COVID 19. Results: In our study, the population affected by SARS-CoV-2 (n=170) showed a significant association between disease severity and troponin levels (median [range] = 4.0 [ Conclusions: The distribution of the troponin values greater than the cut-off in the SARS-CoV-2 population indicates a myocardial suffering independently related to COVID19 infection. This phenomenon may partially explain the high risk of adverse outcome in COVID-19 patients with underlying CVD. Therefore, it may be reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized and personalized treatment strategies.

Coronary microvascular dysfunction (CMD) is related to a broad variety of clinical scenarios in which cardiac microvasculature is morphologically and functionally affected, and it is associated with impaired responses to vasoactive stimuli. Although the prevalence of CMD involves about half of all patients with chronic coronary syndromes and more than 20% of those with acute coronary syndrome, the diagnosis of CMD is often missed, leading to the underestimation of its clinical importance. The established and validated techniques for the measurement of coronary microvascular function are invasive and expensive. An ideal method to assess endothelial dysfunction should be accurate, non-invasive, cost-effective and accessible. There are varieties of biomarkers available, potentially involved in microvascular disease, but none have been extensively validated in this heterogeneous clinical population. The investigation of potential biomarkers linked to microvascular dysfunction might improve the assessment of the diagnosis, risk stratification, disease progression and therapy response. This review article offers an update about traditional and novel potential biomarkers linked to CMD.