Understanding transcatheter edge-to-edge repair "knobology": Advanced catheter steering for different scenarios of transseptal puncture.

Following the introduction in the latest European and American guidelines, transcatheter edge-to-edge repair has become a valid alternative to surgery for ineligible patients. Among the available technologies, MitraClip (Abbott) was the first to be introduced for the percutaneous treatment of mitral regurgitation with the edge-to-edge technique. Although its safety and effectiveness has been widely demonstrated, the optimal procedural results are highly dependent from operators' experience. In this manuscript, we provide a full guide of advanced steering maneuvers of MitraClip in different scenarios of transseptal puncture.

Upper Limbs Muscle Co-Contraction Changes Correlate With The Physical Motor Impairments in CMT.

Background: Subjects with Charcot-Marie-Tooth (CMT) disease show hands impairment which is a relevant problem affecting the quality of life. This symptom is related to muscle weakness and reduced motor coordination of the upper limb. However, most studies focus on lower limb impairment, therefore the investigation of upper limb disability is necessary to identify biomarkers able to monitor disease-specific features and to tailor rehabilitation. Objective: This study aimed at characterizing upper limb muscle co-contraction using the co-contraction index (CCI) in CMT population. Methods: Upper limb kinematic and electromyography (EMG) data were collected from fourteen CMT subjects (6-CMT1A and 8-CMT1X) during motor tasks typical of daily living activities. Rudolph's CCI was used to quantify muscle co-contraction of four muscle pairs acting on shoulder, elbow and wrist. All CMT subjects underwent clinical examination. Thirteen healthy subjects served as the normative reference (HC). Results: CMT1X and CMT1A showed a significant reduction in CCI for distal and proximal muscle pairs compared to HC. Furthermore, CMT1A showed greater values of CCI compared to CMT1X mainly for the axial and axial-to-proximal muscle pairs. Movement speed and smoothness were not altered compared to HC. In addition, EMG metrics showed moderate-to-strong significant correlations with clinical outcomes. Conclusions: CCI was able to quantify disease-specific deficits with respect to the normative reference, highlighting motor control alterations even before motor output impairment. CCI was also sensitive in detecting CMT subtypes-based differences and adopted compensatory strategies. Our findings suggest that CCI can be an outcome measure for CMT disease monitoring and interventional studies.

Pediatric intensive bowel continence rehabilitation training: a retrospective study to evaluate feasibility, tolerance and effectiveness.

BACKGROUND: Pediatric continence dysfunction is not uncommon. It causes long-term disability, impairing quality of life, activities and relationships with pears and can affect until adulthood. A high-risk population are children with Hirschsprung's disease and congenital anorectal malformation. Conservative medical and surgical management of continence dysfunction in this population is deeply described, while the rehabilitation issues are still unexplored. Aim of this study is to preliminary verify the feasibility, tolerance and effectiveness of an intensive technological aided and individualized pelvic floor rehabilitation program for pediatric patients. METHODS: This is a single-center, retrospective observational study. The assessment was performed by collecting demographic data, general and local physical examination and scoring assessment tools (Rintala Continence Score and Wexner Score). The study was conducted in the Rehabilitation Unit of the pediatric Giannina Gaslini Institute, a tertiary care pediatric hospital in Genoa (Italy) between September 2015 to August 2019. We enrolled 31 children; 25 male (80.6%) and six females (19%), aged between 5 and 14 years (mean age 9 years) at the beginning of the training. Twenty children (65.5%) had Hirschsprung's disease, and 11 children (34.5%) had a congenital anorectal malformation. The rehabilitation training program was customized on the compromised function, the anatomic characteristics, the child's age and compliance. The training was aimed at improving tone, strength, endurance of the pelvic floor, compliance and rectal sensitivity, and also the frequency of the bowel movements. All patients enrolled in the study underwent an intensive outpatient treatment lasted 5 days for children older than 7 years; 10 days for younger. The intensive rehabilitation treatment was followed by a continuous home training program. RESULTS: Twenty-nine children (96.8%) completed the training. A global improvement is observed in continence functioning in all the cohort at T1 (P<0.0001), maintained at T3 (P<0.0001) at both Rintala Continence Score and Wexner Score. No adverse effects have been referred. CONCLUSIONS: Our specific pediatric training program for pelvic floor rehabilitation is effective and safe for children with continence dysfunctions after pelvic surgery due to Hirschsprung's disease and anorectal malformations. The continence rehabilitation multimodal program should be integrated in the care of children with continence dysfunctions. It cooperates in the prevention of the long-term health global impairment and also in the reduction of social economic effort.

Microbial signature of plaque and gut in acute coronary syndrome.

Gut microbiota is an emerging editable cardiovascular risk factor. We aim to investigate gut and coronary plaque microbiota, using fecal samples and angioplasty balloons from patients with acute coronary syndrome (ACS), chronic coronary syndrome (CCS) and control subjects. We examined bacterial communities in gut and coronary plaques by 16S rRNA sequencing and we performed droplet digital PCR analysis to investigate the gut relative abundance of the bacterial genes CutC/CntA involved in trimethylamine N-oxide synthesis. Linear discriminant analysis effect size (LEfSe) at the genus and species levels displayed gut enrichment in Streptococcus, Granulicatella and P. distasonis in ACS compared with CCS and controls; Roseburia, C. aerofaciens and F. prausnitzii were more abundant in controls than in patients. Principal component analysis (PCA) of 41 differentially abundant gut taxa showed a clustering of the three groups. In coronary plaque, LEfSe at the genus level revealed an enrichment of Staphylococcus and Streptococcus in ACS, and Paracoccus in CCS, whereas PCA of 15 differentially abundant plaque taxa exhibited clustering of ACS and CCS patients. CutC and CntA genes were more abundant in ACS and CCS than in controls while no significant difference emerged between ACS and CCS. Our results indicate that ACS and CCS exhibit a different gut and plaque microbial signature, suggesting a possible role of these microbiotas in coronary plaque instability.

Targeting Collagen Pathways as an HFpEF Therapeutic Strategy.

Heart failure with preserved ejection fraction (HFpEF) is a complex and heterogeneous clinical syndrome. The prevalence is expected to increase in the coming years, resulting in heart failure with reduced ejection fraction (HFrEF). This condition poses a burden to the global health care system as the number of patients affected by this condition is constantly increasing due to a rising average lifespan. The absence of validated drugs effective in reducing hospitalization rates and mortality may reflect the impossibility of applying a one size fits all approach as in HFrEF, heading for a personalized approach. Available evidence demonstrated the link between collagen quantity and quality alterations, and cardiac remodeling. In the context of fibrosis, collagen cross-linking is strictly involved, displaying two types of mechanisms: enzymatic and non-enzymatic. In the murine model, enzymatic inhibition of fibrosis-inducing protease-activated receptor-1 (PAR1) and transforming growth factor (TGF)-ß signaling appeared to reduce cardiac fibrosis. On the other hand, in the case of non-enzymatic cross-linking, sodium glucose co-transporter type 2 inhibitors (SGLT2is), appeared to counteract the deposition of advanced glycation end-products (AGEs), which in turn contributed to ventricular remodeling. In this review, we address the mechanisms associated with collagen alterations to identify potential targets of cardiac fibrosis in HFpEF patients.

Meta-Inflammation and New Anti-Diabetic Drugs: A New Chance to Knock Down Residual Cardiovascular Risk.

Type 2 diabetes mellitus (DM) represents, with its macro and microvascular complications, one of the most critical healthcare issues for the next decades. Remarkably, in the context of regulatory approval trials, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) proved a reduced incidence of major adverse cardiovascular events (MACEs), i.e., cardiovascular death and heart failure (HF) hospitalizations. The cardioprotective abilities of these new anti-diabetic drugs seem to run beyond mere glycemic control, and a growing body of evidence disclosed a wide range of pleiotropic effects. The connection between diabetes and meta-inflammation seems to be the key to understanding how to knock down residual cardiovascular risk, especially in this high-risk population. The aim of this review is to explore the link between meta-inflammation and diabetes, the role of newer glucose-lowering medications in this field, and the possible connection with their unexpected cardiovascular benefits.

A New Clinical Prediction Rule for Infective Endocarditis in Emergency Department Patients With Fever: Definition and First Validation of the CREED Score.

Background Infective endocarditis (IE) could be suspected in any febrile patients admitted to the emergency department (ED). This study was aimed at assessing clinical criteria predictive of IE and identifying and prospectively validating a sensible and easy-to-use clinical prediction score for the diagnosis of IE in the ED. Methods and Results We conducted a retrospective observational study, enrolling consecutive patients with fever admitted to the ED between January 2015 and December 2019 and subsequently hospitalized. Several clinical and anamnestic standardized variables were collected and evaluated for the association with IE diagnosis. We derived a multivariate prediction model by logistic regression analysis. The identified predictors were assigned a score point value to obtain the Clinical Rule for Infective Endocarditis in the Emergency Department (CREED) score. To validate the CREED score we conducted a prospective observational study between January 2020 and December 2021, enrolling consecutive febrile patients hospitalized after the ED visit, and evaluating the association between the CREED score values and the IE diagnosis. A total of 15 689 patients (median age, 71 [56-81] years; 54.1% men) were enrolled in the retrospective cohort, and IE was diagnosed in 267 (1.7%). The CREED score included 12 variables: male sex, anemia, dialysis, pacemaker, recent hospitalization, recent stroke, chest pain, specific infective diagnosis, valvular heart disease, valvular prosthesis, previous endocarditis, and clinical signs of suspect endocarditis. The CREED score identified 4 risk groups for IE diagnosis, with an area under the receiver operating characteristic curve of 0.874 (0.849-0.899). The prospective cohort included 13 163 patients, with 130 (1.0%) IE diagnoses. The CREED score had an area under the receiver operating characteristic curve of 0.881 (0.848-0.913) in the validation cohort, not significantly different from the one calculated in the retrospective cohort (P=0.578). Conclusions In this study, we propose and prospectively validate the CREED score, a clinical prediction rule for the diagnosis of IE in patients with fever admitted to the ED. Our data reflect the difficulty of creating a meaningful tool able to identify patients with IE among this general and heterogeneous population because of the complexity of the disease and its low prevalence in the ED setting.

Coronary artery plaque rupture and erosion: Role of wall shear stress profiling and biological patterns in acute coronary syndromes.

AIMS: Wall shear stress (WSS) is involved in coronary artery plaque pathological mechanisms and modulation of gene expression. This study aims to provide a comprehensive haemodynamic and biological description of unstable (intact-fibrous-cap, IFC, and ruptured-fibrous-cap, RFC) and stable (chronic coronary syndrome, CCS) plaques and investigate any correlation between WSS and molecular pathways. METHODS AND RESULTS: We enrolled 24 CCS and 25 Non-ST Elevation Myocardial Infarction-ACS patients with IFC (n = 11) and RFC (n = 14) culprit lesions according to optical coherence tomography analysis. A real-time PCR primer array was performed on peripheral blood mononuclear cells for 17 different molecules whose expression is linked to WSS. Computational fluid dynamics simulations were performed in high-fidelity 3D-coronary artery anatomical models for three patients per group. A total of nine genes were significantly overexpressed in the unstable patients as compared to CCS patients, with no differences between IFC and RFC groups (GPX1, MMP1, MMP9, NOS3, PLA2G7, PI16, SOD1, TIMP1, and TFRC) while four displayed different levels between IFC and RFC groups (TNFα, ADAMTS13, EDN1, and LGALS8). A significantly higher WSS was observed in the RFC group (p < 0.001) compared to the two other groups. A significant correlation was observed between TNFα (p < 0.001), EDN1 (p = 0.036), and MMP9 (p = 0.005) and WSS values in the RFC group. CONCLUSIONS: Our data demonstrate that IFC and RFC plaques are subject to different WSS conditions and gene expressions, suggesting that WSS profiling may play an essential role in the plaque instability characterization with relevant diagnostic and therapeutic implications in the era of precision medicine.

GLUT-1/PKM2 loop dysregulation in patients with non-ST-segment elevation myocardial infarction promotes metainflammation.

AIM: The functional capacity of the immune cells is strongly dependent on their metabolic state and inflammatory responses are characterized by a greater use of glucose in immune cells. This study is aimed to establish the role of glucose metabolism and its players [glucose transporter-1 (GLUT-1) and pyruvate kinase isozyme M2 (PKM2)] in the dysregulation of adaptive immunity and inflammation observed in patients with non-ST-segment elevation myocardial infarction (NSTEMI). METHODS AND RESULTS: We enrolled 248 patients allocated to three groups: NSTEMI patients, chronic coronary syndromes (CCS) patients, healthy subjects (HS). NSTEMI patients showed higher expression of GLUT-1 and an enhanced glucose uptake in T cells as compared to CCS patients (p < 0.0001; p = 0.0101, respectively) and HS (p = 0.0071; p = 0.0122, respectively). PKM2 had a prevalent nuclear localization in T lymphocytes in NSTEMI (p = 0.0005 for nuclear versus cytoplasm localization), while in CCS and HS was equally distributed in both compartments. In addition, the nuclear fraction of PKM2 was significantly higher in NSTEMI compared to HS (p = 0.0023). In NSTEMI patients, treatment with Shikonin and Fasentin, which inhibits PKM2 enzyme activity and GLUT-1 mediated glucose internalization, respectively, led to a significant reduction in GLUT-1 expression along with the downregulation of pro-inflammatory cytokine expression. CONCLUSIONS: NSTEMI patients exhibit dysregulation of the GLUT-1/PKM2 metabolic loop characterized by nuclear translocation of PKM2, where it acts as a transcription regulator of pro-inflammatory genes. This detrimental loop might represent a new therapeutic target for personalized medicine.

Quality of life and upper limb disability in Charcot-Marie-Tooth disease: A pilot study.

Charcot-Marie-Tooth (CMT) patients present mainly lower limbs disability, with slowly progressive distal muscle weakness and atrophy, but hands impairment is a relevant problem affecting the quality of life (QoL). The evaluation of the upper limb is of primary importance. Often these patients present subclinical disorders or report difficulties in manipulating objects, with little evidence in the most used outcome measures. We aim to investigate the impact of hand impairment in the perceived QoL of CMT persons and secondly whether the Disability of Arm, Shoulder and Hand (DASH) scale can be useful in assessing upper limb abilities in CMT. We recruited 23 patients with confirmed genetic diagnosis of CMT. We performed a clinical evaluation with Sollerman Hand Function Test (SHFT), Thumb Opposition Test (TOT) and CMT examination score (CMTES). We completed the clinical assessment with DASH scale and the Short form 36 (SF36) questionnaire for a subjective evaluation of upper limb disability and quality of life. All patients also underwent an instrumental evaluation with a hand-held dynamometer measuring hand grip and tripod pinch and a sensor-engineered glove test (SEGT) to evaluate finger opposition movements in a quantitative spatial-temporal way. As expected, we found significant differences between CMT and control group performances in both clinical and instrumental assessment. Concerning QoL, we found that total score of SF36 and the SF36 Physical Composite Score (PCS) correlate with all clinical and instrumental Outcome Measures (OMs), particularly with Tripod pinch strength and TOT, which are considered major determinants of manual dexterity in CMT. DASH scale correlates with most clinical and instrumental OMs. Not surprisingly, we also found a correlation with DASH work, because CMT affects young patients engaged in work activities. However, we found a low correlation with the TOT and the dynamometer suggesting that DASH may not be the best scale for remote monitoring of upper limb disorders in CMT patients. Nevertheless, the results of our study confirm the usefulness of SF36 in recognizing the impact of upper limb disability in these subjects suggesting its use even in the remote monitoring of physical functioning.

Restricted T-Cell Repertoire in the Epicardial Adipose Tissue of Non-ST Segment Elevation Myocardial Infarction Patients.

Aims: Human epicardial adipose tissue, a dynamic source of multiple bioactive factors, holds a close functional and anatomic relationship with the epicardial coronary arteries and communicates with the coronary artery wall through paracrine and vasocrine secretions. We explored the hypothesis that T-cell recruitment into epicardial adipose tissue (EAT) in patients with non-ST segment elevation myocardial infarction (NSTEMI) could be part of a specific antigen-driven response implicated in acute coronary syndrome onset and progression. Methods and Results: We enrolled 32 NSTEMI patients and 34 chronic coronary syndrome (CCS) patients undergoing coronary artery bypass grafting (CABG) and 12 mitral valve disease (MVD) patients undergoing surgery. We performed EAT proteome profiling on pooled specimens from three NSTEMI and three CCS patients. We performed T-cell receptor (TCR) spectratyping and CDR3 sequencing in EAT and peripheral blood mononuclear cells of 29 NSTEMI, 31 CCS, and 12 MVD patients. We then used computational modeling studies to predict interactions of the TCR beta chain variable region (TRBV) and explore sequence alignments. The EAT proteome profiling displayed a higher content of pro-inflammatory molecules (CD31, CHI3L1, CRP, EMPRINN, ENG, IL-17, IL-33, MMP-9, MPO, NGAL, RBP-4, RETN, VDB) in NSTEMI as compared to CCS (P < 0.0001). CDR3-beta spectratyping showed a TRBV21 enrichment in EAT of NSTEMI (12/29 patients; 41%) as compared with CCS (1/31 patients; 3%) and MVD (none) (ANOVA for trend P < 0.001). Of note, 11/12 (92%) NSTEMI patients with TRBV21 perturbation were at their first manifestation of ACS. Four patients with the first event shared a distinctive TRBV21-CDR3 sequence of 178 bp length and 2/4 were carriers of the human leukocyte antigen (HLA)-A*03:01 allele. A 3D analysis predicted the most likely epitope able to bind HLA-A3*01 and interact with the TRBV21-CDR3 sequence of 178 bp length, while the alignment results were consistent with microbial DNA sequences. Conclusions: Our study revealed a unique immune signature of the epicardial adipose tissue, which led to a 3D modeling of the TCRBV/peptide/HLA-A3 complex, in acute coronary syndrome patients at their first event, paving the way for epitope-driven therapeutic strategies.

Molecular Hallmarks of Ischemia with Non-Obstructive Coronary Arteries: The "INOCA versus Obstructive CCS" Challenge.

Up to 4 million patients with signs of myocardial ischemia have no obstructive coronary artery disease (CAD). The absence of precise guidelines for diagnosis and treatment in non-obstructive CAD encourages the scientific community to fill the gap knowledge, to provide non-invasive and less expensive diagnostic tools. The aim of our study was to explore the biological profile of Ischemia with Non-Obstructive Coronary Arteries (INOCA) patients with microvascular dysfunction compared to patients presenting with obstructive chronic coronary syndrome (ObCCS) in order to find specific hallmarks of each clinical condition. We performed a gene expression array from peripheral blood mononuclear cells (PBMCs) isolated from INOCA (n = 18) and ObCCS (n = 20) patients. Our results showed a significantly reduced gene expression of molecules involved in cell adhesion, signaling, vascular motion, and inflammation in INOCA as compared to the ObCCS group. In detail, we found lower expression of Platelet and Endothelial Cell Adhesion Molecule 1 (CD31, p < 0.0001), Intercellular Adhesion Molecule-1 (ICAM1, p = 0.0004), Tumor Necrosis Factor (TNF p = 0.0003), Transferrin Receptor (TFRC, p = 0.002), and Vascular Endothelial Growth Factor A (VEGFA, p = 0.0006) in the INOCA group compared with ObCCS. Meanwhile, we observed an increased expression of Hyaluronidase (HYAL2, p < 0.0001) in INOCA patients in comparison to ObCCS. The distinct expression of molecular biomarkers might allow an early and non-invasive differential diagnosis between ObCCS and INOCA, improving clinical management and treatment options, in the era of personalized medicine.

Incidence and Predictors of Thrombotic Complications in 4742 Patients with COVID-19 or Other Acute Infectious Respiratory Diseases: A Propensity Score-Matched Study.

BACKGROUND: A prothrombotic state, attributable to excessive inflammation, cytokine storm, hypoxia, and immobilization, is a feature of SARS-CoV-2 infection. Up to 30% of patients with severe COVID-19 remain at high risk of thromboembolic events despite anticoagulant administration, with adverse impact on in-hospital prognosis. METHODS: We retrospectively studied 4742 patients with acute infectious respiratory disease (AIRD); 2579 were diagnosed to have COVID-19 and treated with heparin, whereas 2163 had other causes of AIRD. We compared the incidence and predictors of total, arterial, and venous thrombosis, both in the whole population and in a propensity score-matched subpopulation of 3036 patients (1518 in each group). RESULTS: 271 thrombotic events occurred in the whole population: 121 (4.7%) in the COVID-19 group and 150 (6.9%) in the no-COVID-19 group (p < 0.001). No differences in the incidence of total (p = 0.11), arterial (p = 0.26), and venous (p = 0.38) thrombosis were found between the two groups after adjustment for confounding clinical variables and in the propensity score-matched subpopulation. Likewise, there were no significant differences in bleeding rates between the two groups. Clinical predictors of arterial thrombosis included age (p = 0.006), diabetes mellitus (p = 0.034), peripheral artery disease (p < 0.001), and previous stroke (p < 0.001), whereas history of solid cancer (p < 0.001) and previous deep vein thrombosis (p = 0.007) were associated with higher incidence of venous thrombosis. CONCLUSIONS: Hospitalized patients with COVID-19 treated with heparin do not seem to show significant differences in the cumulative incidence of thromboembolic events as well as in the incidence of arterial and venous thrombosis separately, compared with AIRD patients with different etiological diagnosis.

A Novel Monocyte Subset as a Unique Signature of Atherosclerotic Plaque Rupture.

The evaluation of monocyte subset distribution among acute coronary syndrome (ACS) patients according to culprit coronary plaque morphology has never been explored. We evaluated whether there were significant differences in frequency of circulating monocyte subsets isolated from ACS patients according to optical coherence tomography (OCT) investigation of plaque erosion and rupture. We enrolled 74 patients with non-ST-elevation ACS (NSTE-ACS), 21 of them underwent OCT investigation of the culprit coronary plaque and local macrophage infiltration (MØI) assessment. As control, we enrolled 30 chronic coronary syndrome (CCS) patients. We assessed the frequency of monocyte subsets in the whole study population, in reliance on their CD14 and CD16 expression (classical, CM: CD14++CD16-; intermediates, IM: CD14++CD16+; non-classical, NCM: CD14+CD16++). Then, we tested the effect of lipopolysaccharide (LPS) (a CD14 ligand) on peripheral blood mononuclear cells (PBMCs) of NSTE-ACS patients, quantifying the inflammatory cytokine levels in cell-culture supernatants. Our data proved that monocyte subsets isolated from NSTE-ACS patients represent a peculiar biological signature of the pathophysiological mechanism lying beneath atherosclerotic plaque with a ruptured fibrous cap (RFC) as compared with plaque erosion. Moreover, the magnitude of LPS-mediated effects on IL-1ß, IL-6, and IL-10 cytokine release in cell-culture supernatants appeared to be greater in NSTE-ACS patients with RFC. Finally, we described a fourth monocyte population never explored before in this clinical setting (pre-classical monocytes, PCM: CD14+CD16-) that was prevalent in NSTE-ACS patients as compared with CCS and, especially, in patients with RFC and culprit plaque with MØI.

Platelet hyaluronidase 2 enrichment in acute coronary syndromes: a conceivable role in monocyte-platelet aggregate formation.

Acute Coronary Syndromes (ACS) with plaque erosion display dysregulated hyaluronan metabolism, with increased hyaluronidase-2 (HYAL2) expression. However, the expression and the role of this enzyme on platelets has never been explored. We evaluated the platelet's HYAL2 (pltHYAL2) levels on I) stable angina (SA) and II) ACS patients, furtherly sub-grouped in Intact-Fibrous-Cap (IFC) and Ruptured-Fibrous-Cap (RFC), according to Optical Coherence Tomography. We assessed the HYAL2 role through an in vitro model setting of co-cultured monocytes and platelets, before and after treatment with low-molecular-weight hyaluronic acid (HA) as pro-inflammatory stimulus and with or without HYAL2-antibody to inhibit HYAL2 activity. ACS patients exhibit higher pltHYAL2 levels comparing to SA, with the higher expression for IFC group. The addition of HYAL2-antibody significantly reduced the percentage of monocyte-platelet binding, suggesting that pltHYAL2 enrichment at the site of the culprit lesion is a key mediator in the systemic thrombo-inflammatory status of ACS presenting with plaque erosion.

Monocyte-Platelet Aggregates Triggered by CD31 Molecule in Non-ST Elevation Myocardial Infarction: Clinical Implications in Plaque Rupture.

Despite the recent innovations in cardiovascular care, atherothrombosis is still a major complication of acute coronary syndromes (ACS). We evaluated the involvement of the CD31 molecule in thrombotic risk through the formation of monocyte-platelet (Mo-Plt) aggregates in patients with ACS with no-ST-segment elevation myocardial infarction (NSTEMI) on top of dual anti-platelet therapy (DAPT). We enrolled 19 control (CTRL) subjects, 46 stable angina (SA), and 86 patients with NSTEMI, of which, 16 with Intact Fibrous Cap (IFC) and 19 with Ruptured Fibrous Cap (RFC) as assessed by the Optical Coherence Tomography (OCT). The expression of CD31 on monocytes and platelets was measured. Following the coronary angiography, 52 NSTEMIs were further stratified according to thrombus grade (TG) evaluation. Finally, a series of ex vivo experiments verified whether the CD31 participates in Mo-Plt aggregate formation. In patients with NSTEMI, CD31 was reduced on monocytes and was increased on platelets, especially in NSTEMI presented with RFC plaques compared to those with IFC lesions, and in patients with high TG compared to those with zero/low TG. Ex vivo experiments documented an increase in Mo-Plt aggregates among NSTEMI, which significantly decreased after the CD31 ligation, particularly in patients with RFC plaques. In NSTEMI, CD31 participates in Mo-Plt aggregate formation in spite of optimal therapy and DAPT, suggesting the existence of alternative thrombotic pathways, as predominantly displayed in patients with RFC.

Electrocardiographic findings at presentation and clinical outcome in patients with SARS-CoV-2 infection.

AIMS: The main severe complications of SARS-CoV-2 infection are pneumonia and respiratory distress syndrome. Recent studies, however, reported that cardiac injury, as assessed by troponin levels, is associated with a worse outcome in these patients. No study hitherto assessed whether the simple standard electrocardiogram (ECG) may be helpful for risk stratification in these patients. METHODS AND RESULTS: We studied 324 consecutive patients admitted to our Emergency Department with a confirmed diagnosis of SARS-CoV-2 infection. Standard 12-lead ECG recorded on admission was assessed for cardiac rhythm and rate, atrioventricular and intraventricular conduction, abnormal Q/QS wave, ST segment and T wave changes, corrected QT interval, and tachyarrhythmias. At a mean follow-up of 31 ± 11 days, 44 deaths occurred (13.6%). Most ECG variables were significantly associated with mortality, including atrial fibrillation (P = 0.002), increasing heart rate (P = 0.002), presence of left bundle branch block (LBBB; P < 0.001), QRS duration (P <0 .001), a QRS duration of ≥110 ms (P < 0.001), ST segment depression (P < 0.001), abnormal Q/QS wave (P = 0.034), premature ventricular complexes (PVCs; P = 0.051), and presence of any ECG abnormality [hazard ratio (HR) 4.58; 95% confidence interval (CI) 2.40-8.76; P < 0.001]. At multivariable analysis, QRS duration (P = 0.002), QRS duration ≥110 ms (P = 0.03), LBBB (P = 0.014) and presence of any ECG abnormality (P = 0.04) maintained a significant independent association with mortality. CONCLUSION: Our data show that standard ECG can be helpful for an initial risk stratification of patients admitted for SARS-CoV-2 infectious disease.

Are novel outcome measures for Charcot-Marie-Tooth disease sensitive to change? The 6-minute walk test and StepWatch™ Activity Monitor in a 12-month longitudinal study.

Charcot-Marie-Tooth (CMT) is the most common inherited neuropathy, yet has no available pharmacological therapy. Past pharmacotherapy trials failed to provide positive results, possibly due to a poor choice of outcome measures. We previously performed a study in which we validated the 6-minute walk test and StepWatch™ Activity Monitor in CMT. The aim of the current study was to determine if these outcome measures are sensitive to change over a 12-month period. In this longitudinal multicenter study, 149 out of 169 initially enrolled patients were re-evaluated after 12 months using the 6-minute walk test, StepWatch™ Activity Monitor and other outcome measures commonly adopted in CMT disease. Statistical analysis showed a worsening of the CMT-Neuropathy Score (p < 0.05), strength of distal muscles measured by myometry (p < 0.05) and StepWatch™ Activity Monitor outputs (p < 0.05). The 10 meter walking test (p > 0.05), muscular strength as detected by clinical evaluation (p > 0.05), 6-minute walk test (p > 0.05), pain (p > 0.05) and quality of life (p > 0.05) showed no change. In the current study, patients showed clinical worsening over 12 months, confirmed by a reduction of activity as detected by StepWatch™ Activity Monitor. The 6-minute walk test failed to detect change.