Thromboembolic and Bleeding Risk in Cardiac Amyloidosis.

Cardiac amyloidosis represents a spectrum of conditions characterized by the accumulation of insoluble fibrils, resulting in progressive deposition and myocardial dysfunction. The exact mechanisms contributing to the heightened risk of thromboembolic events and bleeding tendencies in cardiac amyloidosis remain unclear. Proteins such as transthyretin in transthyretin amyloidosis and light chains in light chain amyloidosis, along with acute phase proteins in AA amyloidosis, play complex roles in the coagulation cascade, affecting both coagulation initiation and fibrinolysis regulation. The increased occurrence of atrial fibrillation, systolic and diastolic left ventricular dysfunction, and atrial myopathy in patients with cardiac amyloidosis may predispose them to thrombus formation. This predisposition can occur regardless of sinus rhythm status or even with proper anticoagulant management. Bleeding events are often linked to amyloid deposits around blood vessels, which may increase capillary fragility and cause coagulation disturbances, leading to unstable international normalized ratio levels during anticoagulant therapy. Thus, comprehensive risk assessment for both thrombotic and hemorrhagic complications, especially before commencing anticoagulant therapy, is imperative. This review will explore the essential pathophysiological, epidemiological, and clinical aspects of thromboembolic and bleeding risk in cardiac amyloidosis, evaluating the existing evidence and uncertainties regarding thrombotic and bleeding risk assessment and antithrombotic treatment.

High-Risk Sarcoidosis: A Focus on Pulmonary, Cardiac, Hepatic and Renal Advanced Diseases, as Well as on Calcium Metabolism Abnormalities.

Although sarcoidosis is generally regarded as a benign condition, approximately 20-30% of patients will develop a chronic and progressive disease. Advanced pulmonary fibrotic sarcoidosis and cardiac involvement are the main contributors to sarcoidosis morbidity and mortality, with failure of the liver and/or kidneys representing additional life-threatening situations. In this review, we discuss diagnosis and treatment of each of these complications and highlight how the integration of clinical, pathological and radiological features may help predict the development of such high-risk situations in sarcoid patients.

Health equity, care access and quality in headache - part 1.

Current definitions of migraine that are based mainly on clinical characteristics do not account for other patient's features such as those related to an impaired quality of life, due to loss of social life and productivity, and the differences related to the geographical distribution of the disease and cultural misconceptions which tend to underestimate migraine as a psychosocial rather than neurobiological disorder.Global differences definition, care access, and health equity for headache disorders, especially migraine are reported in this paper from a collaborative group of the editorial board members of the Journal of Headache and Pain. Other components that affect patients with migraine, in addition to the impact promoted by the migraine symptoms such as stigma and social determinants, are also reported.

New drugs targeting calcitonin gene-related peptide for the management of migraines.

INTRODUCTION: Significant advances in migraine research have contributed to the development of new drugs for the treatment of migraine. Monoclonal antibodies (mAbs) against Calcitonin Gene-Related Peptide (CGRP) or its receptor and CGRP receptor antagonists (gepants) have been associated with a good safety profile and resulted in an overall efficacy in reducing the number of monthly migraine days both in episodic and chronic forms of migraine. AREAS COVERED: The results from main investigation studies (phase 2 or 3) of CGRP-targeting drugs (both anti-CGRP mAbs and gepants) are reported in this expert-opinion review. EXPERT OPINION: The introduction of new drugs targeting CGRP is a significant breakthrough in the migraine field, and represents a new generation of therapeutic agents that are available to manage migraine. The evaluation of efficacy and safety in the long-term follow-up and the development of trials comparing the available drugs could improve the current knowledge. The economic sustainability of these drugs remains to be clarified, and a cost-cutting campaign should be promoted based on the high burden of migraine.

Approach to COVID-19 in older adults and indications for improving the outcomes.

Background: COVID-19 continues to present challenges in the care of older adults with frailty and/or comorbidities and very old patients, who can be hospitalized with severe COVID-19 despite full vaccination. Frailty is a heterogeneous syndrome characterized by an increased aging-related vulnerability due to a reduced physiological reserve and function of systemic organs, and is associated with an impairment of activities of daily living. Frail older adults remain at elevated risk of mortality from COVID-19 compared to older adults without frailty, and some pre-existing risk factors such as malnutrition, prolonged bed rest, and the association with comorbidities can aggravate the SARS-CoV-2 infection. Furthermore, the severity of COVID-19 can impact on long-term functioning of older patients surviving from the infection. Persistent symptoms are another emerging problem of the post-vaccination phase of pandemic, as most patients suffer from chronic symptoms which can become debilitating and affect the daily routine. Aim of this review: In this complex relationship, the evaluation of COVID-19 in vulnerable categories is still a matter of high interest and personalized care plans based on a comprehensive geriatric assessment, tailored interventions; specific therapeutic algorithms among older adults are thus recommended in order to improve the outcomes.

A highly-detailed anatomical study of left atrial auricle as revealed by in-vivo computed tomography.

The left atrial auricle (LAA) is the main source of intracardiac thrombi, which contribute significantly to the total number of stroke cases. It is also considered a major site of origin for atrial fibrillation in patients undergoing ablation procedures. The LAA is known to have a high degree of morphological variability, with shape and structure identified as important contributors to thrombus formation. A detailed understanding of LAA form, dimension, and function is crucial for radiologists, cardiologists, and cardiac surgeons. This review describes the normal anatomy of the LAA as visualized through multiple imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and echocardiography. Special emphasis is devoted to a discussion on how the morphological characteristics of the LAA are closely related to the likelihood of developing LAA thrombi, including insights into LAA embryology.

Comments and illustrations of the WFUMB CEUS liver guidelines: Rare focal liver lesions - non-infectious, non-neoplastic.

In this series of papers on comments and illustrations of the World Federation for Medicine and Biology (WFUMB) guidelines on contrast enhanced ultrasound (CEUS) the topics of non-infectious and non-neoplastic focal liver lesions (FLL) are discussed. Improved detection and characterization of common FLL are the main topics of these guidelines but detailed and illustrating information is missing. The focus in this paper is on non-infectious and non-neoplastic FLL and their appearance on B-mode, Doppler ultrasound and CEUS features. Knowledge of these data should help to raise awareness of these rarer findings, to think of these clinical pictures in the corresponding clinical situation, to interpret the ultrasound images correctly and thus to initiate the appropriate diagnostic and therapeutic steps in time.

Imaging findings of right cardiac amyloidosis: impact on prognosis and clinical course.

Cardiac involvement from amyloidosis is of growing interest in the overall literature. Despite cardiac amyloidosis (CA) has been considered for a long time a rare disease, the diagnostic awareness is increasing mainly thanks to the improvement of diagnostic softwares and of imaging techniques such as cardiac magnetic resonance  (CMR). Some authors have observed an increase of prevalence rate of CA; moreover it's often underestimated because clinical manifestations are aspecific. The interstitial infiltration of the left ventricle has been extensively studied, while the involvement of the right ventricle (RV) has been less investigated. Involvement of the RV, even in the absence of pulmonary hypertension or clearly left ventricle infiltration, plays an important role as prognostic factor and is useful to achieve an early diagnosis. Therefore, the use of fast and low-cost diagnostic methods such as ultrasound strain of the right ventricle could be used to recognize cardiac amyloidosis early. Herein the importance of evaluating the right ventricular involvement, which can predict the most severe course of the disease also without overt clinical manifestations. The role of imaging, in particular of echocardiography, CMR, and scintigraphy is here reported.

Common Clinical and Molecular Pathways between Migraine and Sarcoidosis.

Migraine and sarcoidosis are two distinct medical conditions that may have some common biological and clinical pathways. Sarcoidosis is a chronic granulomatous disease characterized by the formation of granulomas in various organs, including the lungs, skin, cardiovascular system, lymph nodes, and brain. Migraine is a common comorbidity in sarcoidosis patients and a common neurological disorder characterized by recurrent headaches that can be accompanied by other symptoms, such as nausea, vomiting, and sensitivity to light and sound. There have been several reports of individuals with neurosarcoidosis experiencing migraines, though the exact relationship between the two disorders is not well understood. Both conditions have been associated with inflammation and the activation of the immune system. In sarcoidosis, the formation of granulomas is thought to be an immune response to the presence of an unknown antigen. Similarly, the pain and other symptoms associated with migraines are thought to be caused by inflammation in the brain and the surrounding blood vessels. There is also evidence to suggest an interplay of environmental and genetic factors playing a role in both conditions, but evidence is inconsistent with the hypothesis of shared genetic susceptibility. This review aims to illustrate common clinical and biological pathways between migraine and sarcoidosis, including inflammation and dysregulation of the immune system, with a focus on the cumulative burden of concurrent disorders and therapeutic implications.

Long COVID and especially headache syndromes.

PURPOSE OF REVIEW: This is an expert overview on recent literature about the complex relationship between coronavirus disease 2019 (COVID-19) and headache. RECENT FINDINGS: Long COVID is a clinical syndrome characterized by the presence of persistent symptoms following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Headache is one of the most common symptoms and is described most often as throbbing pain, associated with photo and phonofobia and worsening with physical exercise. In acute COVID-19, headache is usually described as moderate or severe, diffuse and oppressive although sometimes it has been described with a migraine-like phenotype, especially in patients with a previous history of migraine. Headache intensity during acute phase seems to be the most important predictor of duration of headache over time. Some COVID-19 cases can be associated with cerebrovascular complications, and red flags of secondary headaches (e.g. new worsening or unresponsive headache, or new onset of neurological focal signs) should be urgently investigated with imaging. Treatment goals are the reduction of number and intensity of headache crises, and the prevention of chronic forms. SUMMARY: This review can help clinicians to approach patients with headache and infection from SARS-CoV-2, with particular attention to persistent headache in long COVID.

Cardiovascular Morbidity and Mortality Related to Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

Whether non-alcoholic fatty liver disease (NAFLD) is a cardiovascular (CV) risk factor is debated. We performed a systematic review and meta-analysis to assess the CV morbidity and mortality related to NAFLD in the general population, and to determine whether CV risk is comparable between lean and non-lean NAFLD phenotypes. We searched multiple databases, including PubMed, Embase, and the Cochrane Library, for observational studies published through 2022 that reported the risk of CV events and mortality. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for all-cause mortality, CV mortality, myocardial infarction (MI), stroke, atrial fibrillation (AF), and major adverse cardiovascular and cerebrovascular events (MACCE) were assessed through random-effect meta-analysis. We identified 33 studies and a total study population of 10,592,851 individuals (mean age 53±8; male sex 50%; NAFLD 2, 9%). Mean follow-up was 10±6 years. Pooled ORs for all-cause and CV mortality were respectively 1.14 (95% CI, 0.78-1.67) and 1.13 (95% CI, 0.57-2.23), indicating no significant association between NAFLD and mortality. NAFLD was associated with increased risk of MI (OR 1.6; 95% CI, 1.5-1.7), stroke (OR: 1.6; 95% CI, 1.2-2.1), atrial fibrillation (OR: 1.7; 95% CI, 1.2-2.3), and MACCE (OR: 2.3; 95% CI, 1.3-4.2). Compared with non-lean NAFLD, lean NAFLD was associated with increased CV mortality (OR: 1.50; 95% CI, 1.1-2.0), but similar all-cause mortality and risk of MACCE. While NAFLD may not be a risk factor for total and CV mortality, it is associated with excess risk of non-fatal CV events. Lean and non-lean NAFLD phenotypes exhibit distinct prognostic profiles and should receive equitable clinical care.

Sarcoidosis and COVID-19: At the Cross-Road between Immunopathology and Clinical Manifestation.

Coronavirus disease 2019 (COVID-19) has been associated with dysregulation of the immune system featuring inappropriate immune responses, exacerbation of inflammatory responses, and multiple organ dysfunction syndrome in patients with severe disease. Sarcoidosis, also known as Besnier-Boeck-Schaumann disease, is an idiopathic granulomatous multisystem disease characterized by dense epithelioid non-necrotizing lesions with varying degrees of lymphocytic inflammation. These two diseases have similar clinical manifestations and may influence each other at multiple levels, eventually affecting their clinical courses and prognosis. Notably, sarcoidosis patients are at high risk of severe COVID-19 pneumonia because of the underlying lung disease and chronic immunosuppressive treatment. In this narrative review, we will discuss interactions between sarcoidosis and COVID-19 in terms of clinical manifestations, treatment, and pathogenesis, including the role of the dysregulated renin-angiotensin system, altered immune responses involving increased cytokine levels and immune system hyperactivation, and cellular death pathways.

Long COVID headache.

Headache is among the most frequent symptoms persisting or newly developing after coronavirus disease 2019 (COVID-19) as part of the so-called long COVID syndrome. The knowledge on long COVID headache is still limited, however growing evidence is defining the features of this novel condition, in particular regarding clinical characteristics, some pathophysiological mechanisms and first treatment recommendations. Long COVID headache can present in the form of worsening of a preexisting primary headache, or, more specifically, in the form of a new (intermittent or daily) headache starting during the acute infection or after a delay. It often presents together with other long COVID symptoms, most frequently with hyposmia. It can manifest with a migrainous or, more frequently, with a tension-type-like phenotype. Persistent activation of the immune system and trigeminovascular activation are thought to play a role. As there are virtually no treatment studies, treatment currently is largely guided by the existing guidelines for primary headaches with the corresponding phenotype. The present report, a collaborative work of the international group of the Junior Editorial Board of The Journal of Headache and Pain aims to summarize the most recent evidence about long COVID headache and suggests approaches to the diagnosis and treatment of this disorder.

Ultrasound assessment of SARS-CoV-2 pneumonia: a literature review for the primary care physician.

The SARS-CoV-2 pandemic is considered one of the most critical global health emergencies in the last century. The diagnostic approach to the novel coronavirus disease (COVID-19) and its possible complications through a point-of-care-ultrasound (POCUS) evaluation could represent a good solution in the primary care setting. POCUS is a non-invasive technique that can be used outside hospitals to screen COVID-19 patients and their complications safely. Moreover, it offers several applications of diagnostic evaluation not only on lung parenchyma but also to search disease complications, such as the cardiovascular system, even at the patients' home. This narrative review aims to analyse the literature and provide data to primary care physicians engaged in monitoring and treating patients with SARS-CoV-2 infection. Key MessagesPOCUS is an important tool for the diagnostic approach in the primary care setting already before the start of the SARS-CoV-2 pandemic.Portable devices are useful in monitoring the clinical evolution of patients with infection from SARS-CoV-2 at home.The ultrasonographic features can help the general practice physicians to evaluate the presence of lung involvement and to diagnose complications from the SARS-CoV-2 infection involving districts such as the cardiovascular system.

Comorbidities of sarcoidosis.

Sarcoidosis is a heterogeneous disease, which can affect virtually every body organ, even though lungs and intra thoracic lymph nodes are almost universally affected. The presence of noncaseating granulomas is the histopathological hallmark of the disease, and clinical picture depends on the organs affected. Data about interaction between sarcoidosis and comorbidities, such as cardiovascular and pulmonary diseases, autoimmune disorders, malignancy and drug-related adverse events are limited. Several lung conditions can be associated with sarcoidosis, such as pulmonary hypertension and fibrosis, making it difficult sometimes the differentiation between complications and distinctive pathologies. Their coexistence may complicate the diagnosis of sarcoidosis and contribute to the highly variable and unpredictable natural history, particularly if several diseases are recognised. A thorough assessment of specific disorders that can be associated with sarcoidosis should always be carried out, and future studies will need to evaluate sarcoidosis not only as a single disorder, but also in the light of possible concomitant conditions.Key messagesComorbidities in sarcoidosis are common, especially cardiovascular and pulmonary diseases.In the diagnostic workup, a distinction must be made between sarcoidosis-related complaints and complaints caused by other separate disorders. It can be very difficult to distinguish between complications of sarcoidosis and other concomitant conditions.The coexistence of multiple conditions may complicate the diagnosis of sarcoidosis, affect its natural course and response to treatment.

Predictors of Mortality and Cardiovascular Outcome at 6 Months after Hospitalization for COVID-19.

Clinical outcome data of patients discharged after Coronavirus disease 2019 (COVID-19) are limited and no study has evaluated predictors of cardiovascular prognosis in this setting. Our aim was to assess short-term mortality and cardiovascular outcome after hospitalization for COVID-19. A prospective cohort of 296 consecutive patients discharged after COVID-19 from two Italian institutions during the first wave of the pandemic and followed up to 6 months was included. The primary endpoint was all-cause mortality. The co-primary endpoint was the incidence of the composite outcome of major adverse cardiac and cerebrovascular events (MACCE: cardiovascular death, myocardial infarction, stroke, pulmonary embolism, acute heart failure, or hospitalization for cardiovascular causes). The mean follow-up duration was 6 ± 2 months. The incidence of all-cause death was 4.7%. At multivariate analysis, age was the only independent predictor of mortality (aHR 1.08, 95% CI 1.01-1.16). MACCE occurred in 7.2% of patients. After adjustment, female sex (aHR 2.6, 95% CI 1.05-6.52), in-hospital acute heart failure during index hospitalization (aHR 3.45, 95% CI 1.19-10), and prevalent atrial fibrillation (aHR 3.05, 95% CI 1.13-8.24) significantly predicted the incident risk of MACCE. These findings may help to identify patients for whom a closer and more accurate surveillance after discharge for COVID-19 should be considered.

Prognostic Significance of Chest Imaging by LUS and CT in COVID-19 Inpatients: The ECOVID Multicenter Study.

BACKGROUND: Point-of-care lung ultrasound (LUS) score is a semiquantitative score of lung damage severity. High-resolution computed tomography (HRCT) is the gold standard method to evaluate the severity of lung involvement from the novel coronavirus disease (COVID-19). Few studies have investigated the clinical significance of LUS and HRCT scores in patients with COVID-19. Therefore, the aim of this study was to evaluate the prognostic yield of LUS and of HRCT in COVID-19 patients. METHODS: We carried out a multicenter, retrospective study aimed at evaluating the prognostic yield of LUS and HRCT by exploring the survival curve of COVID-19 inpatients. LUS and chest CT scores were calculated retrospectively by 2 radiologists with >10 years of experience in chest imaging, and the decisions were reached in consensus. LUS score was calculated on the basis of the presence or not of pleural line abnormalities, B-lines, and lung consolidations. The total score (range 0-36) was obtained from the sum of the highest scores obtained in each region. CT score was calculated for each of the 5 lobes considering the anatomical extension according to the percentage parenchymal involvement. The resulting overall global semiquantitative CT score was the sum of each single lobar score and ranged from 0 (no involvement) to 25 (maximum involvement). RESULTS: One hundred fifty-three COVID-19 inpatients (mean age 65 ± 15 years; 65% M), including 23 (15%) in-hospital deaths for any cause over a mean follow-up of 14 days were included. Mean LUS and CT scores were 19 ± 12 and 10 ± 7, respectively. A strong positive linear correlation between LUS and CT scores (Pearson correlation r = 0.754; R2 = 0.568; p < 0.001) was observed. By ROC curve analysis, the optimal cut-point for mortality prediction was 20 for LUS score and 4.5 for chest CT score. According to Kaplan-Meier survival analysis, in-hospital mortality significantly increased among COVID-19 patients presenting with an LUS score ≥20 (log-rank 0.003; HR 9.87, 95% CI: 2.22-43.83) or a chest CT score ≥4.5 (HR 4.34, 95% CI: 0.97-19.41). At multivariate Cox regression analysis, LUS score was the sole independent predictor of in-hospital mortality yielding an adjusted HR of 7.42 (95% CI: 1.59-34.5). CONCLUSION: LUS score is useful to stratify the risk in COVID-19 patients, predicting those that are at high risk of mortality.

Accounting for frailty and multimorbidity when interpreting high-sensitivity troponin I tests in oldest old.

BACKGROUND: Older patients evaluated in Emergency Departments (ED) for suspect Myocardial Infarction (MI) frequently exhibit unspecific elevations of serum high-sensitivity troponin I (hs-TnI), making interpretation particularly challenging for emergency physicians. The aim of this longitudinal study was to identify the interaction of multimorbidity and frailty with hs-TnI levels in older patients seeking emergency care. METHODS: A group of patients aged≥75 with suspected MI was enrolled in our acute geriatric ward immediately after ED visit. Multimorbidity and frailty were measured with Cumulative Illness Rating Scale (CIRS) and Clinical Frailty Scale (CFS), respectively. The association of hs-TnI with MI (main endpoint) was assessed by calculation of the Area Under the Receiver-Operating Characteristic Curve (AUROC), deriving population-specific cut-offs with Youden test. The factors associated with hs-TnI categories, including MI, CFS and CIRS, were determined with stepwise multinomial logistic regression. The association of hs-TnI with 3-month mortality (secondary endpoint) was also investigated with stepwise logistic regression. RESULTS: Among 268 participants (147 F, median age 85, IQR 80-89), hs-TnI elevation was found in 191 cases (71%, median 23 ng/L, IQR 11-65), but MI was present in only 12 cases (4.5%). hs-TnI was significantly associated with MI (AUROC 0.751, 95% CI 0.580-0.922, p = 0.003), with an optimal cut-off of 141 ng/L. hs-TnI levels ≥141 ng/L were significantly associated with CFS (OR 1.58, 95% CI 1.15-2.18, p = 0.005), while levels <141 ng/L were associated with the cardiac subscore of CIRS (OR 1.36, 95% CI 1.07-1.71, p = 0.011). CFS, but not hs-TnI levels, predicted 3-month mortality. CONCLUSIONS: In geriatric patients with suspected MI, frailty and cardiovascular multimorbidity should be carefully considered when interpreting emergency hs-TnI testing.