Atherosclerotic Coronary Plaque Features in Patients with Chronic Obstructive Pulmonary Disease and Acute Coronary Syndrome.

Previous studies reported a robust relationship between chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD). Systemic inflammation has been proposed as possible pathogenetic mechanism linking these two entities, although data on atherosclerotic coronary features in COPD patients are lacking. We studied atherosclerotic coronary plaque features in COPD patients presenting with acute coronary syndromes (ACS) by using optical coherence tomography (OCT). ACS patients undergoing intracoronary OCT imaging of the culprit vessel were enrolled. Coronary plaque characteristics and OCT-defined macrophage infiltration (MØI) were assessed by OCT. ACS patients were divided into two groups according to the presence of an established diagnosis of COPD, and plaque features at the culprit site and along the culprit vessel were compared between the groups. Among 146 ACS patients (mean age:66.1±12.7 years, 109 males), 47 (32.2%) had COPD. Patients with COPD had significantly higher prevalence of MØI (78.7% vs. 54.5%, p=0.005) and thin cap fibroatheroma (TCFA) (48.9% vs. 22.2%, p=0.001) at the culprit site. In the multivariate logistic regression, COPD was independently associated with MØI (OR:21.209, CI95%:1.679;267.910, p=0.018) and TCFA at the culprit site (OR:5.345, CI95%:1.386;20.616, p=0.015). Similarly, COPD was independently associated with both MØI (OR:3.570, CI95%:1.472;8.658, p=0.005) and TCFA (OR:4.088, CI95%:1.584;10.554, p=0.004) along the culprit vessel. In conclusion, in ACS patients undergoing OCT imaging of the culprit vessel, COPD was an independent predictor of plaque inflammation and vulnerability. These results may suggest that a higher inflammatory milieu in COPD patients might enhance local coronary inflammation, promoting CAD development and plaque vulnerability.

Coronary Microvascular Dysfunction: A Guide for Clinicians.

Dysfunction of the coronary microvasculature has become increasingly recognized as an important mechanism of myocardial ischemia in patients without obstructive coronary artery disease. The causes and management of coronary microvascular dysfunction remain poorly understood and are still largely based on extrapolation of epicardial coronary artery disease data. Quantification of myocardial blood flow and flow reserve have improved diagnosis, though important questions remain. In this review, we explain current understanding of the spectrum of pathophysiology of coronary microvascular dysfunction, summarize current diagnostic techniques to assess for coronary microvascular dysfunction, and appraise the limited data on management options specifically for patients with coronary microvascular dysfunction.

An update on the mechanisms of Takotsubo syndrome: "At the end an acute coronary syndrome".

Takotsubo syndrome (TTS) is an acute reversible form of myocardial dysfunction, often preceded by a physical or emotional stressful event, that acts as a trigger. Despite, recent advances in the comprehension of the mechanisms leading to TTS, its pathophysiology is far from being completely understood. However, several studies seem to suggest that an acute coronary microvascular dysfunction may represent a crucial pathogenic mechanism involved in TTS occurrence. In this article, we aim to review the complex pathophysiology of TTS and the possible different mechanisms underlying this clinical condition, focusing on the role of coronary microvascular dysfunction and the remaining knowledge's gaps in the field.

Predicting the response to acetylcholine in ischemia or infarction with non-obstructive coronary arteries: The ABCD score.

BACKGROUND AND AIMS: Acetylcholine (ACh) provocation testing can detect vasomotor disorders in patients with ischemia and non-obstructed coronary arteries (INOCA) or myocardial infarction and non-obstructed coronary arteries (MINOCA). We aimed to derive and validate a simple risk score to predict a positive ACh test response. METHODS: We prospectively enrolled consecutive INOCA and MINOCA patients undergoing ACh provocation testing. Patients were split in two cohorts (derivation and validation) according to time of enrolment. The score was derived in 386 patients (derivation cohort) and then validated in 165 patients (validation cohort). RESULTS: 551 patients were enrolled, 371 (67.3%) INOCA and 180 (32.7%) MINOCA. ACh test was positive in 288 (52.3%) patients. MINOCA, myocardial bridge (MB), C-reactive protein (CRP) and dyslipidaemia were independent predictors of a positive ACh test in the derivation cohort. The ABCD (Acute presentation, Bridge, CRP, Dyslipidaemia) score was derived: 2 points were assigned to MINOCA, 3 to MB, 1 to elevated CRP and 1 to dyslipidaemia. The ABCD score accurately identified patients with a positive ACh test response with an AUC of 0.703 (CI 95% 0.652-0.754,p < 0.001) in the derivation cohort, and 0.705 (CI 95% 0.626-0.784, p < 0.001) in the validation cohort. In the whole population, an ABCD score ≥4 portended 94.3% risk of a positive ACh test and all patients with an ABCD score ≥6 presented a positive test. CONCLUSIONS: The ABCD score could avoid the need of ACh provocation testing in patients with a high score, reducing procedural risks, time, and costs, and allowing the implementation of a tailored treatment strategy. These results are hypothesis generating and further research involving larger cohorts and multicentre trials is needed to validate and refine the ABCD score.

Incidence and management of traumatic vertebral artery injuries: wartime experience in Ukraine.

OBJECTIVE: Modern combat-related vertebral artery (VA) injuries are increasingly being diagnosed, but the management of such injuries remains controversial. The authors report the frequency and characteristics of combat-related penetrating VA injuries and the indications for endovascular treatment, as well as analyze their treatment outcomes. METHODS: A 1-year prospective study was completed at a civilian medical center in Dnipro, Ukraine, in all patients with VA injuries sustained during the Russian invasion in the 1st year of war. The authors evaluated the location, type, and severity of the VA injuries and concomitant injuries, as well as the type of intervention and outcomes at 1 month. RESULTS: In total, 279 wounded patients underwent cerebral angiography and 30 (10.8%) patients had VA injuries. All patients were male. There were 28 soldiers and 2 civilians with a mean age of 37.5 years. Four (13.3%) patients had Bissl grade I injuries, 4 (13.3%) had grade II injuries, 4 (13.3%) had grade III injuries (pseudoaneurysm), and 18 (60.0%) had grade IV injuries (occlusion). Four (13.3%) patients underwent emergency open surgical intervention. Fourteen (46.7%) patients underwent endovascular intervention. There was a significant relationship between the anatomical level of the VA injury and surgical intervention (p < 0.05). Endovascular intervention was correlated with the severity of vascular injury to the VA, with 12.5% of the patients receiving intervention for grade I and II lesions and 59.1% receiving intervention for grade III and IV lesions (p < 0.05). The overall mortality in the study group was 6.7% (n = 2), and both died of ischemic complications. CONCLUSIONS: In modern armed conflicts, VA injuries are much more common than reported for previous wars. With the available modern endovascular technology, cerebral angiography is warranted for suspected VA injury and allows for both the diagnosis and treatment of these injuries. Whether endovascular intervention is performed depends on the level and severity of VA injury, severity of concomitant injuries, and presence of collateral circulation.

Time Thresholds for Using Pressure Reactivity Index in Neuroprognostication for Patients With Severe Traumatic Brain Injury.

BACKGROUND AND OBJECTIVES: Severe traumatic brain injury (sTBI) represents a diffuse, heterogeneous disease where therapeutic targets for optimizing clinical outcome remain unclear. Mean pressure reactivity index (PRx) values have demonstrated associations with clinical outcome in sTBI. However, the retrospective derivation of a mean value diminishes its bedside significance. We evaluated PRx temporal profiles for patients with sTBI and identified time thresholds suggesting optimal neuroprognostication. METHODS: Patients with sTBI and continuous bolt intracranial pressure monitoring were identified. Outcomes were dichotomized by disposition status ("good outcome" was denoted by home and acute rehabilitation). PRx values were obtained every minute by taking moving correlation coefficients of intracranial pressures and mean arterial pressures. Average PRx trajectories for good and poor outcome groups were calculated by extending the last daily averaged PRx value to day 18. Each patient also had smoothed PRx trajectories that were used to generate "candidate features." These "candidate features" included daily average PRx's, cumulative first-order changes in PRx and cumulative second-order changes in PRx. Changes in sensitivity over time for predicting poor outcome was then evaluated by generating penalized logistic regression models that were derived from the "candidate features" and maximized specificity. RESULTS: Among 33 patients with sTBI, 18 patients achieved good outcome and 15 patients had poor outcome. Average PRx trajectories for the good and poor outcome groups started on day 6 and consistently diverged at day 9. When targeting a specificity >83.3%, an 85% maximum sensitivity for determining poor outcome was achieved at hospital day 6. Subsequent days of PRx monitoring showed diminishing sensitivities. CONCLUSION: Our findings suggest that in a population of sTBI, PRx sensitivities for predicting poor outcome was maximized at hospital day 6. Additional study is warranted to validate this model in larger populations.

Early management of adult traumatic spinal cord injury in patients with polytrauma: a consensus and clinical recommendations jointly developed by the World Society of Emergency Surgery (WSES) & the European Association of Neurosurgical Societies (EANS).

BACKGROUND: The early management of polytrauma patients with traumatic spinal cord injury (tSCI) is a major challenge. Sparse data is available to provide optimal care in this scenario and worldwide variability in clinical practice has been documented in recent studies. METHODS: A multidisciplinary consensus panel of physicians selected for their established clinical and scientific expertise in the acute management of tSCI polytrauma patients with different specializations was established. The World Society of Emergency Surgery (WSES) and the European Association of Neurosurgical Societies (EANS) endorsed the consensus, and a modified Delphi approach was adopted. RESULTS: A total of 17 statements were proposed and discussed. A consensus was reached generating 17 recommendations (16 strong and 1 weak). CONCLUSIONS: This consensus provides practical recommendations to support a clinician's decision making in the management of tSCI polytrauma patients.

Two-dimensional heavy fermions in the van der Waals metal CeSiI.

Heavy-fermion metals are prototype systems for observing emergent quantum phases driven by electronic interactions1-6. A long-standing aspiration is the dimensional reduction of these materials to exert control over their quantum phases7-11, which remains a significant challenge because traditional intermetallic heavy-fermion compounds have three-dimensional atomic and electronic structures. Here we report comprehensive thermodynamic and spectroscopic evidence of an antiferromagnetically ordered heavy-fermion ground state in CeSiI, an intermetallic comprising two-dimensional (2D) metallic sheets held together by weak interlayer van der Waals (vdW) interactions. Owing to its vdW nature, CeSiI has a quasi-2D electronic structure, and we can control its physical dimension through exfoliation. The emergence of coherent hybridization of f and conduction electrons at low temperature is supported by the temperature evolution of angle-resolved photoemission and scanning tunnelling spectra near the Fermi level and by heat capacity measurements. Electrical transport measurements on few-layer flakes reveal heavy-fermion behaviour and magnetic order down to the ultra-thin regime. Our work establishes CeSiI and related materials as a unique platform for studying dimensionally confined heavy fermions in bulk crystals and employing 2D device fabrication techniques and vdW heterostructures12 to manipulate the interplay between Kondo screening, magnetic order and proximity effects.

Exposome in ischaemic heart disease: beyond traditional risk factors.

Ischaemic heart disease represents the leading cause of morbidity and mortality, typically induced by the detrimental effects of risk factors on the cardiovascular system. Although preventive interventions tackling conventional risk factors have helped to reduce the incidence of ischaemic heart disease, it remains a major cause of death worldwide. Thus, attention is now shifting to non-traditional risk factors in the built, natural, and social environments that collectively contribute substantially to the disease burden and perpetuate residual risk. Of importance, these complex factors interact non-linearly and in unpredictable ways to often enhance the detrimental effects attributable to a single or collection of these factors. For this reason, a new paradigm called the 'exposome' has recently been introduced by epidemiologists in order to define the totality of exposure to these new risk factors. The purpose of this review is to outline how these emerging risk factors may interact and contribute to the occurrence of ischaemic heart disease, with a particular attention on the impact of long-term exposure to different environmental pollutants, socioeconomic and psychological factors, along with infectious diseases such as influenza and COVID-19. Moreover, potential mitigation strategies for both individuals and communities will be discussed.

Comparison between different referral strategies for acute ischemic stroke patients in a hub-spoke emergency stroke network: a real-world experience in south-east Lazio.

AIM: To describe different referral strategies for acute ischemic stroke (AIS) patients in a Hub-Spoke emergency stroke network with their incidence, time metrics and related outcomes. METHODS: Referral paradigms were defined as follows: primary transfer to the comprehensive stroke center (CSC) from a remote region, called mothership (MS); secondary transfer to the CSC from a primary stroke center where intravenous thrombolysis was available, called drip and ship (DS); secondary transfer to the CSC from a community hospital where no reperfusion therapy was available, called ship and drip (SD); primary transfer to the CSC from its catchment area, called direct CSC (dCSC). RESULTS: Among 517 anterior circulation AIS patients treated with mechanical thrombectomy between 2015 and 2020, 16.6% of them were SD, in addition to the well-known referral paradigms of MS (21.8%) and DS (18.1%). This rate grew to 30% when only patients whose place of onset was outside the CSC catchment area were considered. In the SD group, onset to CSC and onset to groin were significantly longer (178±80 min vs. 102±60 min, p<0.001, and 277±77 min vs. 211±61 min, p<0.001, respectively), and the risk of any intracranial hemorrhage (ICH) was significantly higher (OR: 2.514; 95%CI: 1.18-5.35, p=0.017) compared to MS. CONCLUSION: In this hub-spoke stroke network, a high proportion of SD paradigm was found, which was associated with longer times to treatment and higher rates of any ICH. A closer cooperation between hospital stroke physicians, national health system staff, and paramedics is warranted to identify the most appropriate referral strategy for each patient.

Prognostic value of combined fractional flow reserve and pressure-bounded coronary flow reserve: outcomes in FFR and Pb-CFR assessment.

BACKGROUND: Coronary flow reserve (CFR) has an emerging role to predict outcome in patients with and without flow-limiting stenoses. However, the role of its surrogate pressure bounded-CFR (Pb-CFR) is controversial. We investigated the usefulness of combined use of fractional flow reserve (FFR) and Pb-CFR to predict outcomes. METHODS: This is a sub-study of the PROPHET-FFR Trial, including patients with chronic coronary syndrome and functionally tested coronary lesions. Patients were divided into four groups based on positive or negative FFR (cut-off 0.80) and preserved (lower boundary ≥2) or reduced (upper boundary <2) Pb-CFR: Group1 FFR≤0.80/ Pb-CFR <2; Group 2 FFR≤0.80/Pb-CFR≥2; Group 3 FFR >0.80/Pb-CFR<2; Group 4 FFR>0.80/Pb-CFR≥2. Lesions with positive FFR were treated with PCI. Primary endpoint was the rate of major adverse cardiac events (MACEs), defined as a composite of death from any cause, myocardial infarction, target vessel revascularization, unplanned cardiac hospitalization at 36-months. RESULTS: A total of 609 patients and 816 lesions were available for the analysis. At Kaplan-Meier analysis MACEs rate was significantly different between groups (36.7% Group 1, 27.4% Group 2, 19.2% Group 3, 22.6% Group 4, P=0.019) and more prevalent in groups with FFR≤0.80 irrespective of Pb-CFR. In case of discrepancy, no difference in MACEs were observed between groups stratified by Pb-CFR. FFR≤0.80 was associated with an increased MACEs rate (30.2% vs. 21.5%, P<0.01) while Pb-CFR<2 was not (24.5% vs. 24.2% Pb-CFR≥2 P=0.67). CONCLUSIONS: FFR confirms its ability to predict outcomes in patients with intermediate coronary stenoses. Pb-CFR does not add any relevant prognostic information.

Coronary physiology thresholds associated with microvascular obstruction in myocardial infarction.

OBJECTIVES: To ascertain whether invasive assessment of coronary physiology soon after recanalisation of the culprit artery by primary percutaneous coronary intervention is associated with the development of microvascular obstruction by cardiac magnetic resonance in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Between November 2020 and December 2021, 102 consecutive patients were prospectively enrolled in five tertiary centres in Italy. Coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured in the culprit vessel soon after successful primary percutaneous coronary intervention. Optimal cut-off points of IMR and CFR to predict the presence of microvascular obstruction were estimated, stratifying the population accordingly in four groups. A comparison with previously proposed stratification models was carried out. RESULTS: IMR>31 units and CFR≤1.25 yielded the best accuracy. Patients with IMR>31 and CFR≤1.25 exhibited higher microvascular obstruction prevalence (83% vs 38%, p<0.001) and lower left ventricular ejection fraction (45±9% vs 52±9%, p=0.043) compared with those with IMR≤31 and CFR>1.25, and lower left ventricular ejection fraction compared with patients with CFR≤1.25 and IMR≤31 (45±9% vs 54±7%, p=0.025). Infarct size and area at risk were larger in the former, compared with other groups. CONCLUSIONS: IMR and CFR are associated with the presence of microvascular obstruction in STEMI. Patients with an IMR>31 units and a CFR≤1.25 have higher prevalence of microvascular obstruction, lower left ventricular ejection fraction, larger infarct size and area at risk. TRIAL REGISTRATION NUMBER: NCT04677257.

Coronary microvascular obstruction and dysfunction in patients with acute myocardial infarction.

Despite prompt epicardial recanalization in patients presenting with ST-segment elevation myocardial infarction (STEMI), coronary microvascular obstruction and dysfunction (CMVO) is still fairly common and is associated with poor prognosis. Various pharmacological and mechanical strategies to treat CMVO have been proposed, but the positive results reported in preclinical and small proof-of-concept studies have not translated into benefits in large clinical trials conducted in the modern treatment setting of patients with STEMI. Therefore, the optimal management of these patients remains a topic of debate. In this Review, we appraise the pathophysiological mechanisms of CMVO, explore the evidence and provide future perspectives on strategies to be implemented to reduce the incidence of CMVO and improve prognosis in patients with STEMI.

The impact of a community-based music program during infancy on the quality of parent-child language interactions.

The early language environment, especially high-quality, contingent parent-child language interactions, is crucial for a child's language development and later academic success. In this secondary analysis study, 89 parent-child dyads were randomly assigned to either the Music Together® (music) or play date (control) classes. Children were 9- to 15-month old at baseline, primarily white (86.7%) and female (52%). Measures of conversational turns (CTs) and parental verbal quality were coded from parent-child free play episodes at baseline, mid-intervention (month 6), and post-intervention (month 12). Results show that participants in the music group had a significantly greater increase in CT measures and quality of parent verbalization post-intervention. Music enrichment programs may be a strategy to enhance parent-child language interactions during early childhood.

Short-term air pollution exposure and mechanisms of plaque instability in acute coronary syndromes: An optical coherence tomography study.

BACKGROUND AND AIMS: Air pollution is emerging as an important risk factor for acute coronary syndrome (ACS). In this study, we investigated the association between short-term air pollution exposure and mechanisms of coronary plaque instability evaluated by optical coherence tomography (OCT) imaging in ACS patients. METHODS: Patients with ACS undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT. Based on each case's home address, the mean daily exposures to several pollutants, including particulate matter 2.5 (PM2.5), on the same day of ACS and in the immediate days (up to 6 days) prior to the index ACS, were collected. RESULTS: 139 ACS patients were included [69 (49.6%) had PR and 70 (50.4%) IFC]. Patients with PR, compared to those with IFC, had higher PM2.5 exposure levels on the same day of ACS, without differences in the immediate 6 days before index ACS. At multivariate analysis, PM2.5 exposure on the same day of ACS was the only independent predictor of PR [OR = 1.912 per SD (8.6 µg/m3), CI95 % (1.087-3.364), p = 0.025]. Patients with PR presented a steady increase in PM2.5 daily exposure levels in the days preceding the occurrence of ACS, with a peak the day of ACS (p for trend = 0.042) CONCLUSIONS: This study demonstrates for the first time that a higher short-term PM2.5 exposure, on the same day of ACS, is associated with an increased risk of PR as a pathobiological mechanism of coronary plaque instability.

Pathophysiology of coronary microvascular dysfunction.

The term "coronary microvascular dysfunction" (CMD) encompasses several pathogenetic mechanisms resulting in functional and/or structural changes in the coronary microcirculation. CMD often determines angina and myocardial ischemia in a broad spectrum of cardiovascular diseases, including patients with ischemia with non-obstructive coronary arteries or ischemia with obstructive coronary artery disease, infarction with non-obstructive coronary arteries, cardiomyopathies, the Takotsubo syndrome and heart failure, especially heart failure with preserved ejection fraction. In this article, we provide updated evidence regarding the pathophysiological mechanisms underlying CMD across the different cardiovascular diseases, aiming to pave the way for further research and the development of novel strategies for a precision medicine approach.