History Of Disease Research Articles

Cerebellar functional connectivity relates to lower urinary tract function: A 7 Tesla study.

The objective of this study is to explore the functional connectivity (FC) of the cerebellum during the storage phase of micturition, through detecting spontaneous blood-oxygen-level dependent signal between the cerebellum and different brain regions using a high-resolution 7 Tesla magnetic resonance imaging (MRI) scanner. We recruited healthy individuals with no reported history of neurological disease or lower urinary tract (LUT) symptoms. Participants were asked to drink 500 mL of water and then empty their bladders before entering the MRI scanner. They underwent a T1-weighted anatomical scan, followed by an initial (8 min) empty bladder resting state functional MRI (rs-fMRI) acquisition. Once subjects felt the desire to void, a second rs-fMRI scan was obtained, this time with a full bladder state. We established a priori cerebellar regions of interest from the literature to perform seed-to-voxel analysis using nonparametric statistics based on the Threshold Free Cluster Enhancement method and utilized a voxel threshold of p < 0.05. Twenty individuals (10 male and 10 female) with a median age of 25 years (IQR [3.5]) participated in the study. We placed 31 different 4-mm spherical seeds throughout the cerebellum and assessed their FC with the remainder of the brain. Three of these (left cerebellar tonsil, right posterolateral lobe, right posterior lobe) showed significant differences in connectivity when comparing scans conducted with a full bladder to those with an empty bladder. Additionally, we observed sex differences in FC, with connectivity being higher in women during the empty bladder condition. Our initial findings reveal, for the first time, that the connectivity of the cerebellar network is modulated by bladder filling and is associated with LUT function. Unraveling the cerebellum's role in bladder function lays the foundation for a more comprehensive understanding of urinary pathologies affecting this area.

Impact of anesthesia type on surgical outcomes and medical complications in chronic subdural hematoma surgery

BackgroundsChronic Subdural Hematoma (CSDH) is common in elderly patients. Although general anesthesia (GA) has traditionally been used for CSDH surgeries, it may lead to postoperative complications, especially in older patients. We hypothesized that local anesthesia (LA) could reduce postoperative medical complications, including pneumonia, compared to GA. MethodsWe conducted a retrospective study from 2015 to 2019, of medical records of CSDH patients from two hospitals in addition to a comprehensive literature review. Inclusion criteria were a new CSDH diagnoses and treatment with burr-hole craniostomy (BHC) and drain insertion. Patients with recent ipsilateral craniotomies were excluded. Clinical variables included demographics, comorbidities, hematoma characteristics, and post-operative outcomes. ResultsOf 383 eligible patients, 63 underwent BHC under LA (LA group), and 320 under GA (GA group). Both groups exhibited similar baseline characteristics, hematoma characteristics, and surgical outcomes, including postoperative CT findings and ICU stay duration. There was also no significant difference in postoperative bleeding events between the groups. Although patients in the GA group experienced a higher incidence of postoperative pneumonia (3.8 % vs 1.6 %), multivariate analysis revealed that the occurrence of pneumonia was associated with a history of lung disease and preoperative neurological status (OR 7.28, p = 0.018, OR 3.40, p < 0.001, respectively) rather than with the type of anesthesia used. ConclusionOur study suggests that the type of anesthesia does not influence postoperative surgical and medical outcomes, including pneumonia, which is the most common medical complication of BHC for CSDH. Rather, preoperative neurological status and underlying morbidities appear to be more closely related to postoperative medical complications. Future large, prospective studies are needed to validate our findings.

Review article: Measuring disease severity in inflammatory bowel disease - Beyond treat to target.

Inflammatory bowel disease (IBD) follows a heterogenous disease course and predicting a patient's prognosis is challenging. There is a wide burden of illness in IBD and existing tools measure disease activity at a snapshot in time. Comprehensive assessment of IBD severity should incorporate disease activity, prognosis, and the impacts of disease on a patient. This review investigates the concept of disease severity in adults with IBD to highlight key components contributing to this. To perform this narrative review, a Medline search was conducted for full-text articles available at 1st March 2024 using search terms which encompassed disease activity assessment, disease severity, prognosis, natural history of Crohn's disease (CD) and ulcerative colitis (UC), and the burden of IBD. Current methods of disease assessment in IBD have evolved from a focus on the burden of symptoms to one that includes inflammatory targets, genetic, serological, and proteomic profiles, and assessments of quality-of-life (QoL), disability, and psychosocial health. Longitudinal studies of IBD suggest that the burden of illness is driven by disease phenotype, clinical markers of complicated disease course (previous intestinal resection, corticosteroid use, perianal disease in CD, recent hospitalisations in UC), gut inflammation, and the impact of IBD on the patient. Disease severity in IBD can be difficult to conceptualise due to the multitude of factors that contribute to IBD outcomes. Measurement of IBD severity may better encapsulate the full burden of illness rather than gut inflammation alone at a single timepoint and may be associated with longitudinal outcomes.

Endothelial dysfunction markers syndecan-1 and thrombomodulin are associated with higher albuminuria levels in type 2 diabetes with no history of clinical cardiovascular disease

IntroductionIndividuals with type 2 diabetes and increased albuminuria, a well-established marker of microvascular complications, are at a higher risk for cardiovascular disease (CVD) and premature mortality. Therefore, a better understanding of the underlying pathophysiology is needed to improve risk stratification and tailor prevention and intervention. MethodsWe conducted a cross-sectional study including 463 individuals with type 2 diabetes, various degrees of albuminuria and without CVD. We analysed the association between albuminuria and markers of endothelial function (thrombomodulin and syndecan-1), thrombin generation (thrombin-antithrombin complex, prothrombin fragment 1 + 2), fibrinogen, platelet function (activation using soluble plasma selectin and aggregation using Multiplate® Analyzer) using regression models. ResultsIn the study cohort 33 % were women, the mean ± SD age was 65 ± 9 years, and median [IQR] diabetes duration was 15 [9–20] years. In total, 344 (74 %) individuals had normal albuminuria, 87 (19 %) moderately- and 32 (7 %) severely increased albuminuria levels. Higher markers of endothelial function and fibrinogen were independently associated with higher albuminuria levels (p < 0.01). No association between albuminuria and markers of thrombin generation and platelet was demonstrated. ConclusionWe demonstrated an independent association between albuminuria and markers of endothelial function and fibrinogen in individuals with type 2 diabetes and no history of CVD.

Prevalence of cardiomyopathies and myocardial scar in patients with non-complicated premature ventricular beats: a CMR study

Abstract Introduction Frequent or symptomatic premature ventricular beats (PVBs) in subjects with no personal or family history of cardiac disease or sudden death is a recurrent motive for cardiac magnetic resonance (CMR) prescriptions. This represents a significant burden on healthcare services, given the low availability of CMR technique. If CMR is a recommended imaging modality in patients with history of cardiac arrest due to ventricular arrhythmia, sustained ventricular arrhythmias or when first-line tests are abnormal, its diagnostic value in this specific setting has not been evaluated. Purpose To determine the prevalence of significant CMR abnormalities (myocardial fibrosis, arrhythmogenic cardiomyopathies) in patients with no personal nor family history of cardiac disease and non-complicated PVBs. Methods Between September 2010 and July 2021, 416 healthy adults with no personal nor family cardiac disease history underwent CMR at our institution to explore non complicated PVBs, and were retrospectively included (Figure 1). Right and left ventricular (RV/LV) function and dimensions were systematically evaluated on CMR, as the presence of myocardial late gadolinium enhancement (LGE). Criteria for cardiomyopathies (hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), ARVD), the presence and location of myocardial fibrosis were looked after. Results A total of 605 patients were referred for CMR to explore frequent PVBs, representing 14% of all tests performed during this period. Among them, 12 patients (3%) presented significant myocardial abnormalities possibly related to PVBs: 2 patients had sequelae of myocardial infarction and 3 of myocarditis, 1 patient had criteria of HCM and 1 of ARVD, finally 5 presented non-specific myocardial fibrosis (septal mid-wall LGE). In addition, after a mean follow-up of 5 years, there was no death in patients with abnormal CMR, and only 2 patients underwent transcatheter ablation for focal non complicated but symptomatic PVBs. There was no hospitalization for heart failure. Conclusion In patients with non-complicated PVBs and no history of cardiac disease, the rate of cardiomyopathy pattern or myocardial scar on CMR is very low (3%). In this specific population, events were very rare: frequent isolated PVBs, even when associated with myocardial abnormalities, were a benign condition in our study. Given the high volume of patients referred for this indication in daily practice (14% of total CMRs in our center), the limited availability and high costs of CMR, and the difficulties of CMR sequences acquisition in the context of frequent PVBs (possibly leading to misdiagnosis), these data suggest that we should refine the selection of patients undergoing CMR for PVBs exploration.

Sex differences in clinical characteristics, phenotypes, management, and long-term outcomes of myocardial injury: an international cohort study

Abstract Background Several studies have demonstrated sex differences in patients presenting to the emergency department (ED) with myocardial infarction, heart failure or syncope. Whether sex-specific differences in chest pain patients with myocardial injury exist is unknown. Purpose To determine whether sex-specific differences in the clinical characteristics, phenotypes, management, and long-term outcomes of patients with myocardial injury exist. Methods Patients presenting to the ED with chest pain suggestive of MI were consecutively enrolled into a prospective multicenter international diagnostic study. Final diagnoses were centrally adjudicated by two independent cardiologists, applying the fourth universal definition of myocardial infarction, using all available medical records, including serial hs-cTn and cardiac imaging. Follow-ups were performed at 3 months, 1-, 2- and 5-years. The primary outcome was 5-year all-cause mortality. Secondary outcomes included 5-year cardiovascular mortality and non-cardiovascular mortality. Multivariable flexible parametric (Royston-Parmar) models assuming proportional hazards were fitted. Models were adjusted for age, history of coronary artery disease, history of malignancy, diabetes, hypertension, smoking status, history of liver disease, and renal function. Results Among 8046 chest pain patients presenting to the ED, 1158 (14.4%) had myocardial injury, of which 358 (31%) were females and 800 (69%) males. Women were older (79 years, vs. 73 years), had fewer cardiovascular risk factors and comparable non-cardiovascular comorbidities except for lung disease which was more commonly found in men. Myocardial injury phenotypes varied between sexes (Figure). The most common phenotype in both sexes was heart failure, yet it was more common in men (37.2%) than in women (22.3%). The second most common phenotype in women was hypertension (15.4%) and arrhythmia (15.4 %), while in men was myocarditis (17.8 %), followed by arrhythmia (15.8%). Women underwent less invasive coronary angiography (19.8% vs 26.9%) or stress testing (12% vs 21.5%). In the angiographic findings, women presented more often with normal findings (30.4% vs. 19.6%) or mild CAD (20.3% vs. 11.2%) whereas men displayed more frequently 3-vessel disease (14.5% vs. 36.4%), Table. After adjusting for known confounders, women were associated with a lower 5-years risk for all-cause mortality (HR 0.69; 95%CI: 0.56–0.83) and cardiovascular mortality (HR 0.61; 95%CI: 0.46–0.79). No statistically significant difference in non-cardiovascular mortality risk was found (HR 0.79; 95%CI: 0.59-1.04). Conclusions Women presenting with chest pain to the ED and having myocardial injury were less likely than men to undergo coronary angiography or non-invasive cardiac imaging. Long-term risk for all-cause or cardiovascular mortality was lower for women compared to men.Myocardial Injury phenotypesPatient management

Clinical profile and prognosis of Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) in patients with previous Acute Coronary Syndrome (ACS)

Abstract Introduction Myocardial infarction with non-obstructed coronary arteries (MINOCA) may occur in patients with a personal history of ischaemic heart disease, making diagnosis even more difficult. In addition, the role of cardiovascular risk factors, which are well known in patients with acute myocardial infarction with obstructed arteries (MICAD), is less well defined in MINOCA. The aim of this study is to define the clinical characteristics, risk factors and long-term prognosis in patients with MINOCA and previous acute coronary syndrome (ACS). Methods A prospective, analytical, observational study was designed. Included all patients admitted to our centre with ACS between 2016 and 2023 in which a coronary angiography was performed. Patients were classified as MINOCA according to the definition of the 2020 European ACS guidelines. MINOCA patients with and without a history of previous ischaemic heart disease were compared. At follow-up, MACE was defined as all-cause death, hospitalisation, reinfarction and stroke. The median follow-up was 43 [IQR 20-71]. Results A total of 136 patients were included, of whom 17 had a history of ACS. The proportion of men was significantly higher in the group with previous ACS (82% vs 48%; p=0.008). Patients with a history of ACS had higher rates of smoking (71% vs 51%, p=0.139), more night work (80% vs 39%, p=0.017) and less stress (33% vs 61%, p=0.152). They also had more peripheral vascular disease (24% vs 3%, p=0.005), diabetes (41% vs 19%, p=0.042), dyslipidaemia (71% vs 43%, p=0.04) and a higher rate of atrial fibrillation (29% vs 9%, p=0.032). However, despite a higher rate of previous ventricular dysfunction (24% vs 3%, p=0.005), they had lower troponin levels on admission (62 [IQR 37-368] vs 152 [IQR 49-424]). We found no differences in the other comorbidities analysed (Table 1). On admission, patients with previous ACS had significantly more non-ST-segment elevation (29% vs 10%, P=0.05) and received more beta-blocker treatment (82% vs 57%, p=0.046). When analysing the mechanism of infarction, patients without previous ACS were more likely to have vasospasm and coronary embolism. However, there was a significantly higher rate of type II AMI (41% vs 18%, p=0.044) in the group with previous ACS. During follow-up, patients with a history of ACS are more likely to have a new infarction (7% vs 3%, p=0.3) or stroke (14% vs 6%, p=0.2). There was also a trend towards a higher incidence of MACE in patients with prior ACS, although this did not reach statistical significance (HR 2.379, 95% IC 0,883-6,405) (Table 2). Conclusion MINOCA patients with a history of ACS have distinct and worse epidemiological features in which classic cardiovascular risk factors play a significant role, with more ventricular dysfunction and atrial fibrillation. In addition, they appear to have a worse prognosis with increased cardiovascular complications. That might suggest a more MICAD-like profile.

Vascular complications in patients with peripheral veno-arterial extracorporeal membrane oxygenation: clinical-echocardiographic characteristics and predictors

Abstract Introduction Veno-arterial Extracorporeal membrane oxygenation (VA ECMO) is a salvage intervention in patients with cardiogenic shock (CS), and cardiac arrest (CA) refractory to standard therapies. Lower limb ischemia associated with peripheral VA ECMO is frequent, and is considered a serious complication with a significant impact on the morbidity and mortality. Purpose The aim of this study was to describe the clinical-echographic parameters and analyze predictors related to vascular complications in patients with peripheral VA ECMO. Methods The study was a single-center cohort analysis. It included all consecutive adult patients with peripheral femoro-femoral VA ECMO due to refractory cardiogenic shock (CS) or cardiac arrest (CA) between March 2014 and December 2022. Patients with central cannulation were excluded. The primary endpoint was evidence of vascular complications resulting in surgical intervention. A multivariate logistic regression model was used to adjust for variables of interest. Results The study included 83 patients (65± 12 years, 54% male). The main previous diagnosis was necrotic ischemic cardiomyopathy (33%), and the most frequent indication was postcardiotomy (40.9%), mainly in SCAI D (85.5%). Cardiopulmonary resuscitation was performed in 18.1%. Femoro-femoral cannulation was percutaneuos in 95.2%. Most patients had intra-aortic balloon pump (87.1%) and distal percutaneous cannula (88.8%). A total of 18 patients presented vascular complications (21.7%): 2 patients (11.1%) amputation, 5 patients (27.7%) compartment syndrome requiring fasciotomy, 9 patients (50.0%) thrombectomy, and 2 patients (11.1%) a surgical resolution post decannulation due to AV fistula. The median duration of VA ECMO was 5 days (IQR 2-8). Among the ultrasound variables, the systolic peak velocity (SPV) in the distal territory (tibioperoneal segment) had a median of 22 cm/sec (IQR 10-30). Pulsatile spectral Doppler flow in the cannulated limb was evidenced in 42 patients (50.6%) of total population, and only in 3 patients (16.6%) with vascular complications. The survival rate from VA ECMO was 57.8%, and the survival rate to discharge 42.1%. In-hospital mortality of patients with or without vascular complications did not show statistically significant differences (54.2 % vs 58.2 %, p= 0.26). After multivariate analysis, distal territory SPV less than 20 cm/sec (OR: 2.1, 95%CI: 1.3 – 12.1, p: 0.03), as well as history of previous vascular disease, were associated with a higher number of vascular complications (OR: 2.5, 95% CI: 1.5 – 10.1, P; 0.02). Conclusions Vascular complications in patients with femoro-femoral VA ECMO remain frequent and constitute an important cause of morbidity. Decreased peak systolic velocities in the cannulated tibio-peroneal territory, as well as a history of previous vascular disease were significantly associated with a higher rate of vascular complications.

Orthostatic blood pressure changes and incident atrial fibrillation in patients with hypertension: Insights from the SPRINT trial

Abstract Background Exaggerated orthostatic changes in systolic blood pressure (SBP) were associated with adverse cardiovascular events. However, the predictive role of SBP hyperactivity to standing on incident atrial fibrillation (AF) is unclear. Purpose We aim to assess the association between orthostatic SBP changes and incident AF. Methods We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial), a randomized controlled trial comparing intensive (&amp;lt;120 mm Hg) and standard (&amp;lt;140 mm Hg) SBP interventions in participants with hypertension. Participants with standing SBP &amp;lt;110 mm Hg were not eligible for randomization according to the SPRINT protocol. Participants without AF who had seated and standing SBP measurements at baseline and available baseline or follow-up ECG were included in this analysis. Orthostatic SBP changes were defined as standing SBP minus seated SBP. Patients were grouped into tertiles of orthostatic SBP changes. AF was ascertained from the standard 12-lead ECG obtained at baseline, year 2, year 4, a close-out visit, and any visit when suspected of serious adverse events. We used Cox proportional regression models and restricted spline curves to assess the association of orthostatic SBP changes with incident AF. Results Among 8,455 participants included in this analysis, 327 incident AF cases occurred during follow-up. The restricted spline curve depicted a U-shaped relationship between orthostatic SBP changes and incident AF in the unadjusted model (P for nonlinearity = 0.012) (Figure 1). After adjusting for age, female, race, smoking, alcohol use, history of cardiovascular disease, history of chronic kidney disease, and body mass index, a SBP increase ≥ 6 mm Hg to standing was independently associated with a 43% higher risk of incident AF (HR: 1.43; 95% CI: 1.07-1.90; P = 0.014) compared to nonsignificant orthostatic SBP changes (&amp;gt;-4 mm Hg to &amp;lt;6 mm Hg). A SBP decrease ≥ 4 mm Hg to standing showed a nonsignificant higher risk of developing AF compared to SBP changes of &amp;gt;-4 mm Hg to &amp;lt;6 mm Hg (Figure 2). In subgroup analysis, the results presented a similar tendency to the main result. Sensitivity analyses also generated consistent results while additionally adjusting for seated and standing blood pressure or heart rate. Conclusion In this post hoc analysis of the SPRINT trial, exaggerated SBP increase to standing independently predicts incident AF.Figure 1Figure 2

Plasma protein profile associated with a family history of early-onset coronary heart disease

Abstract Introduction Although family history of coronary heart disease (CHD) is an established risk factor for subsequent CHD, its relation to the circulating proteome is unknown. Proteins linked to coronary atherosclerosis in subjects with a family history could uncover new pathophysiological mechanisms of heritable CHD. Purpose Firstly, we aimed to study the protein profile associated with a family history of early-onset CHD. Secondly, we aimed to identify proteins among which family history was an effect modifier for the association between each protein and coronary atherosclerosis. Methods Plasma levels of proteins were assessed with Olink panels CVD-II and -III in the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort. The coronary segment involvement score (SIS) was assessed from computed tomography angiography. Subjects without known CHD were cross-referenced with national registers to identify records of myocardial infarction or coronary revascularization in any parent before 55 or 65 years of age in males and females, respectively. The associations between a family history of CHD and each protein were studied with linear regression adjusted for age, sex and study site, using a False Discovery Rate (FDR) of 5%. Associations were subsequently adjusted for cardiovascular risk factors. Similarly, associations between each protein and SIS were modelled linearly with an FDR of 5%. For significant proteins, the statistical interactions between each protein and family history for the association between proteins and SIS were studied. Results Of 4,251 subjects, 9.5% had a family history CHD. 43 proteins were significantly associated with family history, and when adjusted for risk factors 29 protein associations remained significant (p&amp;lt;0,05) [Figure 1]. The strongest associations were observed for cathepsin D, paraoxonase 3, interleukin-1 receptor antagonist protein and renin. 79 proteins were associated with SIS at FDR&amp;lt;5%, and family history was a significant effect modifier 18 for proteins [Figure 2]. The strongest modifying effects were observed for transferrin receptor protein 1 (β 0.64, 95% CI 0.25–1.04 for those with family history vs β -0.04, 95% CI -0.14–0.06 in those without, p for interaction=0.001), LDL-receptor (β 0.68, 95% CI 0.36–1.00 vs β 0.18, 95% CI 0.08–0.26) and tissue-type plasminogen activator (β 0.45, 95% CI 0.19–0.70 vs β 0.13, 95% CI 0.05–0.21). Conclusion We found that 43 proteins, with biological features of inflammation and vascular function, were associated with a family history of early-onset CHD. Most were also linked to the coronary atherosclerosis burden. Notably, 18 biomarkers, among them transferrin receptor protein 1, LDL-receptor and tissue-type plasminogen activator, exhibited strong statistical interactions with family history in the association with SIS, indicating that they are of particular importance for the genetic susceptibility and the pathophysiology of heritable CHD.

A systematic assessment of myocardial involvement and cardiovascular events up to six months in patients hospitalised with COVID-19

Abstract Background Retrospective cohort studies indicate that myocardial injury occurs in approximately 25% of patients hospitalised with COVID-19. However, prospective studies with a systematic assessment of myocardial involvement and major adverse cardiovascular events (MACE) after COVID-19 are scarce. Purpose The primary objective was to determine the incidence of MACE within six months of hospitalisation. MACE was defined as a composite of cardiac death, sudden death, life-threatening ventricular arrhythmia's, heart failure, non-fatal myocardial infarction, and/or non-fatal stroke. The main secondary objective was to determine the frequency of other cardiac complications not covered by this definition. Methods We conducted a prospective multicenter cohort study in 13 Dutch medical centers. Adult patients hospitalised with COVID-19 were consecutively recruited (May 2021-April 2023). Exclusion criteria were age ≥70 years, a history of new cardiac disease in the past six months, or dependency in the activities of daily living. Cardiac involvement was evaluated by a standardised healthcare pathway that was implemented in participating hospitals. All patients received an electrocardiogram, transthoracic echocardiogram, and troponin measurement at admission and at six months follow-up. Furthermore, a questionnaire was distributed at three and six months after admission to collect information on post-COVID symptomatology. Results In total 190 patients were included, median age of 57 years [IQR 48; 64], mostly male (n=110, 60%) and white (n=136, 72%). Cardiovascular risk factors were present in 116 (61.1%) patients and 33 (17.4%) had a history of cardiac disease. At admission, troponin was above the upper limit of normal in 68 (35.8%) patients. Seven (3.7%) patients died during follow-up. The cumulative incidence of MACE was 2.6% at discharge with no additional events during follow-up. Other cardiac complications were detected in 18 (9.5%) patients during admission with 3 (1.6%) additional events at six months follow-up. Supraventricular tachycardias (n=8, 4.2%) were the most common cardiac complication. Other complications were myocarditis (n=2, 1.1%), pericarditis (n=1, 0.5%), non-sustained ventricular tachycardia (n=1, 0.5%), and other arrhythmias or conduction disorders (n=5, 2.6%). At six months follow-up, three (2.3%) patients reported chest pain, with one requiring a percutaneous coronary intervention. Palpitations and dizziness were experienced by 88.9% and 83.3% of patients three months after admission but the prevalence of these symptoms decreased to 9.8% and 11.8% at six months. Conclusion With a systematic assessment, one in three patients hospitalized with COVID-19 have elevated troponin levels at admission. However, the overall incidence of MACE within six months is low. Palpitations and dizziness are commonly reported after discharge but these symptoms disappeared for most participants within six months.

Applicability of VICTORION-1 PREVENT Criteria to the US Population

Abstract Background VICTORION-1 PREVENT (V-1P) is an ongoing randomized clinical trial comparing inclisiran sodium 300mg every six months with placebo for primary prevention in patients with high cardiovascular (CV) risk. Purpose We evaluated the generalizability of V-1P trial enrollment criteria to the US population to understand the demographic and CV health characteristics of the trial target population. Methods We included data from the National Health and Nutrition Examination Survey (N=25,531, 2015-March 2020), a nationally representative sample of the US population. Enrollment criteria similar to V-1P were applied. Nonpregnant adults 40-79 years with low-density lipoprotein cholesterol (LDL-C) of 70-189 mg/dL were included. 10-year risk for CV disease was determined using the American Heart Association race-free 10-year PREVENT risk equations. Individuals with 10-year risk &amp;gt;20% or 7.5%-19.9% with two risk enhancing factors at baseline were included. Risk enhancing factors included elevated high sensitivity C-reactive protein (≥2 mg/L), inflammatory arthritis, estimated glomerular filtration rate &amp;lt;60 ml/min/1.73 m2, metabolic syndrome, or early family history of CV disease. Patients with history of atherosclerotic CV disease or liver disease were excluded. Estimates of demographics and health characteristics were nationally representative using survey weights. Results Among US adults, 21,576,506 (standard error [SE]: ±1,258,255) meet eligibility criteria for V-1P (weighted estimate). This represents 8.8% of all US adults or 15.1% of US adults 30-79 years. The V-1P eligible population had a mean age of 65.3 years (SE: ±0.5 years), and 55.0% (SE: ±2.5%) were female. Compared with the US adult population (≥18 years), V-1P eligible population had a higher mean body mass index (32.6 ± 0.3 kg/m2 vs 29.5 ± 0.2 kg/m2) and higher rates of obesity (61.0% ± 2.1% vs 40.0% ± 1.1%) (Table). V-1P eligible population also had higher mean systolic blood pressure (133.9 ± 1.0 mmHg vs 121.7 ± 0.3 mmHg), similar mean diastolic blood pressure (72.6 ± 0.8 mmHg vs 71.8 ± 0.2 mmHg), and higher rates of hypertension (85.8% ± 2.0% vs 45.9% ± 1.1%). Mean hemoglobin A1c percent (6.3 ± 0.1 vs 5.7 ± 0.02), fasting blood sugar (127.7 ± 1.9 mg/dL vs 109.2 ± 0.6 mg/dL), and diabetes rates (39.7% ± 2.6% vs 13.1% ± 0.7%) were higher in the V-1P eligible population. Mean low-density lipoprotein cholesterol (115.8 ± 1.5 mg/dL vs 110.2 ± 0.8 mg/dL) and fasting triglycerides (137.6 ± 5.0 mg/dL vs 110.4 ± 1.7 mg/dL) were higher, while mean high-density lipoprotein cholesterol was lower (49.9 ± 0.8 mg/dL vs 54.8 ± 0.4 mg/dL). The distribution of key CV risk factors is shown in the Figure. Conclusion V-1P enrollment criteria apply to many patients. These patients have significant cardiometabolic risk factor burden, and effective preventive therapies could have substantial health impact.

Prediction of 10-year risk for recurrent atherosclerotic cardiovascular events in a secondary prevention population: Insights from CHART-2 and Suita studies in the Japanese population

Abstract Background Despite the European Society of Cardiology (ESC) guidelines advocating risk prediction models for secondary prevention in established atherosclerotic cardiovascular disease (ASCVD) patients, such models for Japanese individuals remain limited, owing to their comparatively lower ASCVD risk than Western populations. Given this gap, there is a need to develop tailored risk assessment tools for Japanese ASCVD patients to optimize secondary prevention strategies. Purpose Leveraging data from two large-scale, long-term cardiovascular cohorts in Japan, our aim was to develop and externally validate a 10-year risk model predicting recurrent cardiovascular events among patients with established ASCVD. Methods The CHART-2 and Suita studies, large-scale prospective observational multicenter cohort studies in Japan, served as the primary data sources for this investigation. From the CHART-2 study, which comprised 3,560 patients with a history of coronary artery disease or ischemic stroke, we derived our risk model. External validation was conducted using data from the Suita study, which included 445 patients with similar ASCVD backgrounds. The primary outcome of interest was a composite endpoint encompassing cardiovascular death, myocardial infarction, or stroke. Variable selection was performed based on clinically relevant factors previously employed in established risk scores (SMART, REACH, and TRS 2°P risk scores). Logistic regression was utilized for model development, and the predictive performance was assessed using the C-index. Results Over a median follow-up of 10.1 years, the derivation cohort experienced 756 cardiovascular events. Patients in the derivation cohort had an average age of 68.9 ± 10.6 years, with 91% and 24% having a history of coronary artery disease and ischemic stroke, respectively. Using logistic regression, the multivariate model revealed a higher recurrent risk associated with several factors including age, smoking status, systolic blood pressure, diabetes, renal function, number of ASCVD events, atrial fibrillation, lipid levels, left ventricular systolic dysfunction, and statin use. A simple risk score based on these predictors demonstrated a &amp;gt;5-fold gradient of 10-year recurrent risk with a C-index of 0.65 (95% CI 0.63-0.68, Figure). The prediction model was externally validated in the Suita study wit 245 cardiovascular events and a median follow-up of 10.4 years, showing good discriminative ability with a C-index of 0.64 (95% CI 0.60–0.68). Conclusion Our newly developed prediction model offers a valuable tool for identifying individuals at heightened risk of recurrent cardiovascular events over a 10-year period, thereby facilitating more targeted and effective secondary prevention strategies tailored to the unique characteristics of Japanese ASCVD patients.

Hospital and one-year outcomes following a hypertensive urgency or emergency: a major challenge

Abstract Introduction Hypertension is an important issue, and recommendations are constantly evolving based on the latest research findings and directions. Hypertensive emergencies are defined as a severe elevation of blood pressure associated with organ damage. End organ damage was defined as the presence of one of the following findings: encephalopathy, ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, acute heart failure, acute coronary syndrome, or aortic dissection. Furthermore, malignant hypertension is a HE characterized by small artery fibrinoid necrosis in the kidney, retina and brain. All these definitions are confusing, but what about their evolution? Objective:The present study aims to analyze the mortality in the short and long term (12months), the survival of the hypertensive patients, the frequency of malignant hypertension and hypertensive retinopathy. Methods For this purpose, we conducted a prospective study including all patients who followed or were diagnosed with hypertension and admitted to the emergency department for hypertensive urgency/emergency, from January to March 2023; after that, we studied the evolution of these patients for one year until January 2024. Demographic data, disease history, blood pressure, clinical presentation on admission, target organ involvement, ophthalmological examination and evolution during hospitalization were studied. Statistical analysis was performed using SPSS software. Preeclampsia and chronic renal failure were excluded.Result: Our work brought together 300 patients, mainly female, with an average age of 63.4. One hundred fifteen were admitted for HE and 185 for HU. The most common presenting symptoms at admission were headache, focal neurologic deficit and dyspnea. Malignant hypertension was identified in 9 patients based on optical coherence tomography angiography by identifying subclinical microvascular damage, and investigation is still in progress searching for hypertensive retinopathy grade III-IV Keith-Wagner in the second group. Patients were mainly hospitalized for hypertensive emergencies. Regarding their therapeutic management, except for the acute lowering of blood pressure in stroke, there was no consensus initially; ideally was to determine which organs are affected to assess the need for specific intervention other than lowering blood pressure. Overall, 49 had died from HE n=44/115(vs n=5/185 for HU). Of these, 33 have died at the Hospital (mortality was higher for HE and attributable to neurovascular emergencies rather than cardiovascular emergencies) and ten at 12 months. Conclusion Properly managing patients who come to the Emergency Department for BP elevation faces many difficulties. Can we still talk about hypertensive emergencies/urgency, discuss retinal lesions, and the importance of hypertension monitoring? However, all those definitions can be potentially life-threatening; these results justify better follow-up and treatment for these patients.

Mitral valve phenotypes in SMAD3-related thoracic aortic disease: insights from the Montalcino Aortic Consortium

Abstract Background SMAD3 pathogenic variants (PV) predispose to heritable thoracic aortic aneurysms and dissections (HTAD). Mitral annular disjunction (MAD) associated with mitral valve prolapse (MVP) and mitral regurgitation (MR) was identified as a potential new marker of disease severity in Marfan syndrome. The prevalence and prognostic impact of these mitral phenotypes in other forms of HTAD are less known. Purpose We hypothesize that mitral abnormalities are increased in SMAD3-related HTAD and are associated with increased risk for valve and aortic complications. Methods The Montalcino Aortic Consortium (MAC) registry has enrolled participants with PV in 15 HTAD genes. Subjects &amp;gt;16 years old with complete imaging and clinical data were included in this study. MVP was defined according to current guidelines. MR was classified as mild, moderate, or severe. MAD was defined by a &amp;gt;3-millimeter gap between the posterior mitral valve leaflet hinge point and the inferolateral myocardium as confirmed by direct measurement of echocardiogram images. Frequencies of MVP, MR, and MAD were compared between MAC participants with SMAD3 PV and other HTAD PV. Associations between clinical and echo characteristics and the composite outcome of arrhythmia, aortic surgery, aortic dissection, or congestive heart failure was evaluated with multivariable logistic regression. Results In 671 MAC participants (129 with SMAD3 PV, 36 [IQR 19-51] years, 49% female), the prevalence of MVP was 15% and the prevalence of MR was 22%. Both MVP (31/129, 24%, vs. 67/542, 12%, OR 2.2 [1.4-3.6], P&amp;lt;0.001) and MR (40/129, 31%, vs. 108/542, 20%, OR 1.8 [1.2-2.8], P&amp;lt;0.006) were more common in participants with SMAD3 PV compared to other PV and were further enriched in cases with SMAD3 missense PV compared to loss of function PV (MR or MVP: 26/48, 54% vs. 7/30, 23%, OR 3.9 [1.4-10.8], P&amp;lt;0.007). Images were available from 238 MAC participants (67 with SMAD3 PV) to assess for MAD. MAD (29/67, 43%, vs. 28/171, 16%, OR 3.9 [2.1-7.3], P&amp;lt;0.0001), or the composite of MR, MVP, or MAD (42/67, 63%, vs. 69/171, 35%, OR 3.2 [1.8-5.7], P&amp;lt;0.0001) was more common with SMAD3 PV compared to other PV (Figure 1). Twelve participants with SMAD3 PV (18%) had prominent mitral phenotypes (&amp;gt;mild MR, &amp;gt;10 mm MAD, or MAD with MVP) but no significant aortic dilation (Z&amp;lt;3). When controlling for age and sex, MR or MVP, but not MAD, was independently associated with the composite outcome (OR 16 [2.4-110], Figure 2). Conclusion Mitral valve pathology, including MVP, MR, and MAD, is increased in individuals with SMAD3 PV compared to other HTAD PV. Prominent mitral phenotypes related to SMAD3 missense PV may identify a high-risk subgroup with adverse cardiovascular outcomes. Because congenital mitral disease may be the primary presenting feature of SMAD3 PV, genetic testing for HTAD should be considered for such patients, especially if they also have a family history of thoracic aortic disease.

The added value of deep learning to submaximal exercise electrocardiogram for the 10-year prediction of major adverse cardiovascular and cerebrovascular events

Abstract Background The added value of exercise ECG data to traditional risk factors in predicting cardiovascular events remains unclear. Deep learning of ECG signals has demonstrated state-of-the-art performance in detecting subtle abnormalities indicative of cardiovascular disease. We investigated whether deep learning analysis of exercise ECGs could improve the prediction of major cardiovascular and cerebrovascular events (MACCE) with respect to established risk models in a large population-based cohort. Purpose To assess the added value of submaximal exercise ECG measurements to established cardiovascular risk prediction models. Methods We obtained ECG recordings from 41,076 UK Biobank participants without cardiovascular disease (CVD) who underwent a submaximal exercise ECG test. We obtained ECG recordings from 41,076 UK Biobank participants without cardiovascular disease (CVD) who underwent a submaximal exercise ECG test. We created two deep neural network ECG risk scores: one derived from conventional ECG parameters, measured at rest, peak exercise and late-stage recovery, and another based on the complete ECG (Q-ECG). We assessed the added value of conventional ECG parameters and Q-ECG risk scores to the UK's current prediction algorithm (QRISK3). We estimate the association between ECG parameters and MACCE, using Cox Proportional hazard models, following adjustment for traditional risk factors. All models were internally validated via 5-fold cross-validation and 1000 bootstrap iterations. Predictive performance was evaluated using Harrel's C-index, Net Reclassification Index (NRI) and net benefit. Findings: Incident MACCE was reported in 4,082 (9.9%) individuals in the study population and 3,463(9.7%) individuals with valid ECG parameters over a median follow-up period of 12.5 years. We found combined conventional ECG and Q-ECG scores were independently associated with MACCE, following adjustment for multiple testing: adjusted hazard ratio [HZ] = 1.76 (95% CI:1.63-1.91); HZ = 1.14 (95% CI:1.10-1.18), respectively, per standard deviation increase. Both conventional ECG parameters and Q-ECG were predictive of MACCE, independent of clinical risk factors, C-index = 0.64 (95%CI 0.63-0.65); net benefit = 0.09(95% CI 0.07 - 0.11) and C-index = 0.56 (95% CI 0.55-0.57); net benefit = 0.07(95% CI 0.05 - 0.09). ECG measurement's modestly improved model discrimination over the bassline QRISK3 risk score when combined with QRISK3 risk factors for conventional markers and Q-ECG score, respectively; ΔC-index 0.03 (95% CI: 0.02 – 0.04) and ΔC-index 0.03 (95% CI: 0.02 – 0.03); However, we observed no significant improvements in classification at the current recommended threshold of 10%. Conclusion In individuals without a history of prior cardiovascular disease, ECG measures independently predict the risk of MACCE. When combined with QRISK3, neural-network-derived ECG risk scores marginally improve cardiovascular risk prediction over QRISK3.

Myocardial SGLT2 expression and cardiac remodeling in patients with severe aortic stenosis: the BIO-AS Study

Abstract Background Cardiac remodeling plays a major role in the prognosis of patients with aortic stenosis (AS) and could impact the benefits of aortic valve replacement. Blood and tissue biomarkers have a differential pattern and expression level in patients with AS, which may retain a pathophysiological role in cardiac remodeling and metabolism. However, the data available are limited and contradictory. Aim Our study aimed to evaluate the expression of sodium-glucose cotransporter 2 (SGLT2) gene and protein in patients with severe AS stratified in high gradient (HG) and low flow-low gradient (LF-LG) AS and its association with cardiac functional impairments. Methods Gene expression and protein levels of main biomarkers of cardiac fibrosis (Galectin-3, sST2, Serpin-4, PINP, PICP, Collagen, TGF-b), inflammation (GDF-15, IL-6, NF-kB), oxidative stress (SOD1, SOD2), and cardiac metabolism (NHE, PPAR-a, PPAR-g, GLUT1, and GLUT4) were evaluated in blood samples and heart biopsies of 45 patients with AS. Results Our study showed SGLT2 gene and protein hyper-expression in patients with LF-LG AS, compared to controls and HG AS (p&amp;lt;0.05). These differences remained significant even after adjusting for age, gender, body mass index, history of diabetes mellitus, arterial hypertension, and coronary artery disease. SGLT2 gene expression was positively correlated with: i) TGF-b (r=0.72, p&amp;lt;0.001) and collagen (r=0.73, p&amp;lt;0.001) as markers of fibrosis; ii) NF-kB (r=0.36, p&amp;lt;0.01) and myocardial IL-6 (r=0.68, p&amp;lt;0.001) as markers of inflammation: iii) SOD2 (r=-0.38, p&amp;lt;0.006) as a marker of oxidative stress; iv) GLUT4 (r= 0.33, p&amp;lt;0.02) and PPAR-a (r=0.36, p&amp;lt;0.01) as markers of cardiac metabolism (Figure 1). Conclusion In patients with LF-LG AS, SGLT2 gene and protein were hyper-expressed in cardiomyocytes and associated with myocardial fibrosis, inflammation, and oxidative stress. The hyper-expression of the SGLT2 gene and protein in patients with LF-LG might pave the way for using SGLT2-Is in this subset population, with the potential to improve the outcomes of AVR and reduce the likelihood of re-hospitalization within one year.Figure 1

The Influence of Anthropometric Factors on Renal mpMRI: Insights From Regional Analysis.

Multiparametric MRI (mpMRI) provides detailed insights into renal function, but the impact of anthropometric factors on renal imaging is not fully understood. To investigate regional correlations between mpMRI parameters and age, body mass index (BMI), and body surface area (BSA). Prospective, cross-sectional observational study. Twenty-nine healthy volunteers (44.5 ± 18.3 years, 18 females) without a history of renal disease. 3-T, pseudo-continuous arterial spin labeling, multi-echo gradient-recalled echo, diffusion-weighted imaging, T1 and T2 mapping. Bilateral kidneys were segmented into nine concentric layers (outer cortex to inner regions) and nine equiangular sections (lower to upper pole). Key parameters (renal blood flow [RBF], , apparent diffusion coefficient [ADC], T1 and T2 maps) were correlated with age, BMI, and BSA. Differences in parameters between age and BMI groups were also evaluated. Spearman correlation, Mann-Whitney U test, and rank-biserial correlation coefficient for effect size. A P-value <0.05 was considered statistically significant. RBF correlated negatively with age in all regions and BMI in inner layers and lower pole. ADC negatively correlated with BMI (significance was not reached in layers 2, 7, 8; P-value = 0.06-0.12) and BSA in layers 1-7. T1 negatively correlated with age in inner regions and lower medial pole. Significant positive correlations were found between age and (outermost layer, upper pole), age and T2 (inner and cranial-caudal regions), as well as BMI and T2 (except upper pole; P-value = 0.06). Significant differences between age groups were observed for RBF (all regions), (outermost and second innermost layers, central lateral region), T1 (innermost layer), and T2 (upper medial pole). Between BMI groups, ADC (middle layers, upper medial pole) and T2 (outermost and inner layers, lower pole to lateral region) differed significantly. Intrarenal variance of mpMRI parameters correlated with age, BMI, and BSA. 4 TECHNICAL EFFICACY: Stage 1.

Propensity score-matched analysis in isolated left ventricular dilation and non-ischaemic dilated cardiomyopathy

Abstract Background The presence and extent of late gadolinium enhancement (LGE) assessed by cardiac magnetic resonance imaging (CMR) are strong prognosticators of death in patients with non-ischaemic dilated cardiomyopathy (DCM), defined by the current guidelines as left ventricular (LV) dilation and left ventricular ejection fraction (LVEF)&amp;lt;50%. Although the current guidelines defined the concept of "isolated LV dilation" as LV dilation with preserved LVEF≥50%, the prognostic value of the LGE granularity including its extent, location and pattern is not established in this population. Purpose To assess the prognostic value of the concept of "LGE granularity" including its extent, location, and pattern for predicting all-cause death above traditional prognosticators in patients with LV dilation and reduced LVEF (i.e. DCM) or preserved LVEF (i.e. isolated LV dilation), separately. Methods Between 2008 and 2021, all consecutive patients with DCM and isolated LV dilation without ICD or history of sustained ventricular arrhythmia referred for CMR were included in two centres. All patients with history of coronary artery disease or myocarditis were excluded. The primary outcome was all-cause death using the French National Registry of Death. A 1:1 propensity score matching was performed to balance baseline characteristics in patients with DCM vs. those with isolated LV dilation. Cox regressions were performed to determine the prognostic value of each LGE findings. Results Of 2,752 patients analysed (age 52±8 years, 56% male), 408 (15%) patients died after a median (interquartile range) follow-up of 9 (7-12) years. A total of 737 (27%) patients had LGE. Patients with DCM had a higher rate of death than patients with isolated LV dilation (16% versus 13%, p=0.02). In the propensity-score matched population (N=1,084 in DCM subgroup and N=1,084 in isolated LV dilation), the LGE presence was associated with death (HR=2.98, 95%CI: 1.97-4.50, p&amp;lt;0.001). In isolated LV dilation patients with LGE (N=265), the LGE extent (HR=1.41, 95%CI:1.09-1.83, p=0.009), the presence of LGE in multiple areas (HR=3.86, 95%CI: 1.73-8.61, p&amp;lt;0.001) and the septal location (HR=2.97, 95%CI:1.37-6.46, p=0.006) were strong prognosticators of death after adjustment for traditional prognosticators. Similarly, in DCM patients with LGE (N=268), the LGE extent (HR=1.42, 95% CI:1.07-1.89, p=0.014), the presence of LGE in multiple areas (HR=8.41, 95%CI: 3.32-21.3, p&amp;lt;0.001) and the septal location (HR=6.65, 95% CI: 3.02-14.6, p&amp;lt;0.001) were strongly associated with death after adjustment. Conclusion In a large cohort of DCM and isolated LV dilation patients, the concept of "LGE granularity" was independently associated with all-cause death after adjustment for all traditional prognosticators in both DCM and isolated LV dilation. These results suggest the existence of a continuum between isolated LV dilation and DCM, and that CMR assessment could improve the risk stratification in this population.

Effects of deferment of clinic visit on cardiovascular outcomes during COVID-19 outbreak: a prospective cohort study

Abstract Background Current guidelines recommend 3-6 months interval outpatient follow-up for patients with cardiovascular (CV) diseases and risk factors such as hypertension, diabetes mellitus (DM) and dyslipidemia. The impact of longer follow-up intervals is unclear. From 2020 to 2022, due to the infection control measures for COVID-19 pandemic, many patients voluntarily deferred their scheduled clinic visits. This provided us with an opportunity to study the impact of prolonged visit intervals on management CV risk factors. Purpose We aimed to investigate the impact of prolonged clinic visit intervals on CV outcomes and CV risk factor management among patients with CV diseases. Methods Patients with at least 1 CV risk factor (DM, hypertension, dyslipidemia, or a history of CV disease) were recruited from cardiology outpatient clinics from a tertiary teaching hospital from 2020-2022. Patients who opted to defer their appointment (Deferred group) were compared to those who attended their scheduled appointment (Normal group). The primary outcomes were composite major adverse cardiovascular events (MACE) of myocardial infarction, stroke, or CV-related death. The secondary outcomes were any unscheduled hospitalizations, suboptimal DM control (haemoglobin A1C &amp;gt;7%) or hyperlipidemia (LDL &amp;gt; 1.4 mmol/L). Results Out of the 455 patients recruited from outpatient clinics, 162 patients (35.6%) opted to defer their scheduled clinic visit (mean age 64.7 ± 12, 37.7% female), and 293 patients (mean age 64.5 ± 10, 36.2% female) continued to attend their appointments. The mean appointment interval was 226 days for the normal group and 582 days for the deferred group (p&amp;lt; 0.001). There was no significant difference in the primary outcome of MACE between the ‘Normal’ group and the ‘Deferred’ group (2.5% vs 0.6%, p=NS). The number of patients with suboptimal DM control (11.4% vs 21.9%, p = 0.029) was higher in the deferred group, whereas suboptimal hyperlipidemia (73.1% vs 77.1%, p=NS) was not statistically different. There were a total of 27 of unscheduled hospitalizations, among which the majority was for CV-related events (63.0%). Patients in the ‘Deferred’ group had higher rates of unscheduled hospitalization (12.3% vs 2.4%, p &amp;lt; 0.001) and higher rate of CV-related hospitalization compared to the ‘Normal’ group (6.2% vs 2.4%, p=0.041). Conclusion Our prospective data demonstrates that a prolonged clinic visit interval of more than 365 days was not associated with significant increase in adverse CV event or worsening of lipid control. However, prolonged clinic visit interval was associated with worse DM control and more frequent unscheduled hospitalization. More frequent medical contact might allow timely management of medical emergency at the outpatient setting and contribute to the lower rate of hospitalization in the routine follow-up group.