Subclinical Abnormalities Research Articles

Association of Thyroid Dysfunction in Individuals ≥ 65 Years of Age With Subclinical Cardiac Abnormalities.

The relationship between thyroid dysfunction and measures of myocardial disease in older individuals remains to be defined. To evaluate the impact of thyroid dysfunction on structure and function of the left heart chambers and blood markers of cardiac disease. Cross-sectional analysis of the Cardiovascular Health Study, a community-based cohort of older individuals recruited from 4 urban areas in the United States. Of 3163 participants studied, 2477 were euthyroid, 465 had subclinical hypothyroidism (SCH), 47 overt hypothyroidism (OH), 45 endogenous (endo) subclinical hyperthyroidism (endo-SCT), and 129 had exogenous (exo) SCT due to thyroid hormone supplementation. Participants underwent clinical evaluation, blood sampling and biomarker measurement, 2-dimensional and speckle tracking echocardiography for assessment of left heart myocardial deformation, circulating biomarkers of diastolic overload (NT-proBNP), fibrosis (sST2, gal-3), and cardiomyocyte injury (hs-cTnT). SCH was associated with higher NT-proBNP (beta = 0.17, P = .004), whereas OH was associated with higher hs-cTnT (beta = 0.29, P = .005). There were also suggestive associations of SCH with higher sST2, as well as endo-SCT with higher gal-3 and lower (worse) left atrial reservoir strain. Left ventricular longitudinal strain and end diastolic strain rate did not differ significantly from euthyroid participants in SCH, OH, or exo-SCT. In this free-living elderly cohort, subclinical and overt hypothyroidism were associated with abnormalities of blood biomarkers consistent with diastolic overload and myocardial necrosis respectively, whereas subclinical hyperthyroidism tended to be associated with myocardial fibrosis and decreased left atrial strain. Our findings could represent stage B heart failure and illuminate distinct aspects of the pathobiology of heart disease related to thyroid gland dysfunction with potential clinical implications.

Kiosk 7R-FA-04 - Subclinical Cardiac Abnormalities in Thrombotic Thrombocytopenic Purpura (TTP) Survivors

Kiosk 7R-FA-04 - Subclinical Cardiac Abnormalities in Thrombotic Thrombocytopenic Purpura (TTP) Survivors

Development and validation of a machine learning model for clinical wellness visit classification in cats and dogs.

Early disease detection in veterinary care relies on identifying subclinical abnormalities in asymptomatic animals during wellness visits. This study introduces a model designed to distinguish between wellness and other types of veterinary visits. The purpose of this study is to validate the use of a visit classification model compared to manual classification of veterinary visits by three board-certified veterinarians. The algorithm was initially trained using a Gradient Boosting Machine model with a dataset of 11,105 clinical visits from 2012 to 2017 involving 655 animals (85.3% dogs and 14.7% cats) across 544 U.S. veterinary practices. Three validators were tasked with classifying 400 visits, including both wellness and other types of visits, selected randomly from the same database used for initial model training, aiming to maintain consistency and relevance between the training and application phases; visit classifications were subsequently categorized into "wellness" or "other" based on majority consensus among validators to assess the model's performance in identifying wellness visits. The model demonstrated a specificity of 0.94 (95% CI: 0.91 to 0.96), implying its accuracy in distinguishing non-wellness visits. The model had a sensitivity of 0.86 (95% CI: 0.80 to 0.92), indicating its ability to correctly identify wellness visits as compared to the annotations provided by veterinary experts. The balanced accuracy, calculated as 0.90 (95% CI: 0.87 to 0.93), further confirms the model's overall effectiveness. The model exhibits high specificity and sensitivity, ensuring accurate identification of a high proportion of wellness visits. Overall, this model holds promise for advancing research on preventive care's role in subclinical disease identification, but prospective studies are needed for validation.

Clinical Management of Non-alcoholic Steatohepatitis and the Role of the Cardiologist

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of fat-associated liver conditions that increase risk of cardiovascular disease and mortality. The diagnosis and clinical management of NAFLD remain a challenge for cardiologists. Our group performed a systematic review in PubMed of the relationship between NAFLD and cardiovascular disease, identifying 35 relevant articles. NAFLD is likely to be the liver’s expression of metabolic syndrome and increases the risk of several cardiovascular diseases, including coronary artery disease, stroke, heart failure and electrical disorders, and chronic kidney disease. Echocardiography is a useful tool to check early subclinical abnormalities in heart structure and function linked to NAFLD progression, such as cardiac diastolic impairment or epicardial fat thickness. Currently, NAFLD is predominantly managed by lifestyle changes with the aim of weight loss, based on the Mediterranean diet and intense exercise training. Despite the lack of approved drugs for NAFLD, new potential treatments, mainly glucagon-like peptide-1 agonists or sodium–glucose cotransporter 2 inhibitors, could change cardiologists’ approach to this pathology.

Relation between the Epicardial Fat Thickness and the Cardiac Conduction System in Children and Adolescents with Diabetes

Introduction: Atherosclerosis in patients with type 1 diabetes starts early in childhood with subclinical abnormalities. The epicardial fat thickness (EFT) is a novel method for detecting these early changes. Furthermore, electrocardiographic markers may be altered in patients with diabetes owing to early cardiovascular changes. This study aimed to determine the relationship between EFT and electrocardiographic markers in children with type 1 diabetes mellitus. Methods: Children with type 1 diabetes who were followed up at the Alexandria University Children’s Hospital Diabetes Clinic were enrolled in this study. The study recruited three groups of participants, including 20 patients with a diabetes duration of less than 5 years, 20 patients with a diabetes duration of 5 years or more, and 20 healthy controls. All participants were evaluated with emphasis on anthropometric measurements, fasting blood glucose levels, and lipid profile. HbA1c levels were measured in the cohort with diabetes. All participants underwent electrocardiography for measurement of P-wave dispersion, corrected QT interval and its dispersion, and Tp-e measurement. Echocardiography was performed to measure the EFT. Results: Among all participants, EFT was significantly higher in children with a diabetes duration of ≥5 years (p = 0.009). Furthermore, P-wave dispersion was significantly prolonged in children with diabetes compared to that in nondiabetics (p = 0.041). There was a statistically significant correlation between EFT and P-wave dispersion in patients with diabetes aged ≥5 years (p = 0.021). Conclusions: Measurement of EFT by echocardiography is a novel and easy way to predict early cardiovascular changes in children with diabetes, including conduction system disorders.

Prevalence and Predictors of Subclinical Cardiomyopathy in Patients With Type 2 Diabetes in a Health System.

Diabetic cardiomyopathy (DbCM) is characterized by subclinical abnormalities in cardiac structure/function and is associated with a higher risk of overt heart failure (HF). However, there are limited data on optimal strategies to identify individuals with DbCM in contemporary health systems. The aim of this study was to evaluate the prevalence of DbCM in a health system using existing data from the electronic health record (EHR). Adult patients with type 2 diabetes mellitus free of cardiovascular disease (CVD) with available data on HF risk in a single-center EHR were included. The presence of DbCM was defined using different definitions: (1) least restrictive: ≥1 echocardiographic abnormality (left atrial enlargement, left ventricle hypertrophy, diastolic dysfunction); (2) intermediate restrictive: ≥2 echocardiographic abnormalities; (3) most restrictive: 3 echocardiographic abnormalities. DbCM prevalence was compared across age, sex, race, and ethnicity-based subgroups, with differences assessed using the chi-squared test. Adjusted logistic regression models were constructed to evaluate significant predictors of DbCM. Among 1921 individuals with type 2 diabetes mellitus, the prevalence of DbCM in the overall cohort was 8.7% and 64.4% in the most and least restrictive definitions, respectively. Across all definitions, older age and Hispanic ethnicity were associated with a higher proportion of DbCM. Females had a higher prevalence than males only in the most restrictive definition. In multivariable-adjusted logistic regression, higher systolic blood pressure, higher creatinine, and longer QRS duration were associated with a higher risk of DbCM across all definitions. In this single-center, EHR cohort, the prevalence of DbCM varies from 9% to 64%, with a higher prevalence with older age and Hispanic ethnicity.

Red cell abnormalities characterized by ektacytometry in children with cholestasis.

Spur-cell anemia sometimes accompanies cholestasis. We postulated that even in the absence of spur-cells, cholestasis might alter red blood cell (RBC) osmotic fragility and deformability. Therefore, we assessed these RBC measures by ektacytometry in pediatric patients. We conducted a single center, prospective, cross-sectional investigation of RBC membrane characteristics by ektacytometry in pediatric patients with intra- and extrahepatic cholestasis followed at Cincinnati Children's Hospital Medical Center. We measured red cell membrane fragility and deformability in 17 patients with cholestasis and 17 age-matched controls without cholestasis. Patients with cholestasis had decreased RBC osmotic fragility compared to controls, with a significant left shift in Omin, indicating increased RBC surface-to-volume ratio. One showed spur cell morphology. However, the other 16 had no spurring, indicating that ektacytometry is a sensitive method to detect RBC membrane abnormalities. Left shift of Omin positively correlated with serum conjugated bilirubin levels and even more negatively with serum vitamin E concentration. This study suggests that subclinical red blood cell membrane abnormalities exist in most pediatric patients with cholestasis, increasing risk for hemolysis when subjected to oxidative stress. Hence minimizing pro-oxidants exposure and maximizing antioxidant exposure is advisable for this group. NCT05582447 https://clinicaltrials.gov/ct2/show/NCT05582447?cond=Cholestasis&cntry=US&state=US%3AOH&city=Cincinnati&draw=2&rank=2 . Spur cell anemia due to decreased red cell osmotic fragility and decreased deformability has been reported among patients with cholestasis. Ektacytometry is a reliable, reproducible method to measure red cell osmotic fragility and deformability. Few data describe red cell osmotic fragility or deformability in patients with cholestasis who may or may not have spur cell anemia. Ektacytometry shows that red cell osmotic fragility and deformability are decreased in many children with cholestasis even when spur cell anemia has not yet occurred. Factors associated with decreased osmotic fragility include elevated serum bilirubin, elevated serum bile acids, and decreased serum vitamin E.

Cardiac Abnormalities in Relation to the Disease Activity Index Among Systemic Lupus Erythematosus Patients in a Tertiary Hospital: A Cross-Sectional Study.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue disorder involving multiple organs and systems. Cardiovascular involvement in SLE patients is a major cause of morbidity and mortality. Although subclinical cardiac abnormalities exist among SLEpatients, they are rarely screened for. Echocardiography has been demonstrated to be a useful tool for the early diagnosis of cardiac abnormalities in SLE patients, many of which are clinically silent. Early recognition of cardiovascular abnormalities is vital for the prompt initiation of the appropriate management.This study aims to determine the prevalence of various structural and functional cardiac abnormalities among SLE patients and to determine its association with the modified SLE Disease Activity Index 2000 (modified SLEDAI-2K). The study was a cross-sectional study of SLE patients at the Korle-Bu Teaching Hospital (KBTH), Accra, Ghana, from June to December 2021. The setting was the rheumatology outpatient clinic of the KBTH and included adult men and women, 18 years and above, diagnosed with SLE with no known cardiac abnormalities. The baseline demographic and clinical characteristics of the participants were determined. A detailed transthoracic echocardiogramwas performed for all patients. The frequency of common cardiac pathologies was determined and compared between those with a high modified SLEDAI-2K and those with a low modified SLEDAI-2K. Ninety-nine SLE patients participated in the study with a mean age of 35.12 years. Females formed the majority (90.9%) of the participants. The mean age at diagnosis of SLE was 28.7 years and the mean disease duration was 4.6 years. All of the participants were on at least two disease-modifying medications. The mean modified SLEDAI-2K score was 9.1. Thirty-five percent (35%) of the patients had mild to moderately active disease and 39% had severely active disease. Sixty-six (66%) out of the severely active disease group had abnormal echocardiographic findings, while 28% of those with mild to moderate disease had abnormal echocardiographic findings. Echocardiographic abnormalities were found in 56 patients (47%), out of which 8.7% had valvular involvement, 15.7% had diastolic dysfunction, 5.2% had left ventricular hypertrophy (LVH), and 0.9% had left ventricular systolic dysfunction (LVSD). About 12% of the participants had pulmonary hypertension and 1% had pericardial involvement. The odds of echocardiographic abnormalities were 13.7 times higher in SLE patients with high disease activity compared to those with low disease activity (odds ratio (OR) = 13.714, 95% confidence interval (CI) = 3.804-49.442, p < 0.001). There was no significant association between cardiac abnormalities and SLE duration. No significant correlation between cardiac abnormalities and modified SLEDAI-2K score was found. Conclusion:Cardiac abnormalities, especially left ventricular diastolic dysfunction (LVDD),valvular involvement, and pulmonary hypertension, are common in SLE patients.For SLE patients, especially those with active diseases, echocardiographicassessment should be considered in the management of SLE patients to enable early detection of cardiac abnormalities, early treatment, and thus a decrease in morbidity and mortality associated with cardiovascular involvement in SLE patients.

Surveillance cardiopulmonary exercise testing can risk-stratify childhood cancer survivors: underlying pathophysiology of poor exercise performance and possible room for improvement

BackgroundAsymptomatic childhood cancer survivors (CCS) frequently show decreased exercise performance. Poor exercise performance may indicate impaired future cardiovascular health.MethodsCardiopulmonary exercise testing (CPET) was performed in asymptomatic off-treatment CCS (age ≥ 10 years). Patients were divided into Normal and Poor performance groups by %predicted maximum VO2 at 80%. Both peak and submaximal CPET values were analyzed.ResultsThirty-eight males (19 Normal, 19 Poor) and 40 females (18 Normal, 22 Poor) were studied. Total anthracycline dosage was comparable among 4 groups. The body mass index (BMI), although normal, and weight were significantly higher in Poor groups. Peak heart rate (HR) and peak respiratory exchange ratio (RER) were comparable in all four groups. Peak work rate (pWR)/kg, peak oxygen consumption (pVO2)/kg, peak oxygen pulse (pOP)/kg, and ventilatory anaerobic threshold (VAT)/kg were significantly lower, whereas heart rate (HR) increase by WR/kg (ΔHR/Δ[WR/kg] was significantly higher in Poor groups. Simultaneously plotting of weight & pVO2 and ΔHR/ΔWR & ΔVO2/ΔHR revealed a distinct difference between the Normal and Poor groups in both sexes, suggesting decreased skeletal muscle mass and decreased stroke volume reserve, respectively, in Poor CCS. The relationship between VAT and pVO2 was almost identical between the two groups in both sexes. Ventilatory efficiency was mildly diminished in the Poor groups.ConclusionsDecreased skeletal muscle mass, decreased stroke volume reserve, and slightly decreased ventilatory efficiency characterize Poor CCS in both sexes. This unique combined CPET analysis provides useful clinical biomarkers to screen subclinical cardiovascular abnormality in CCS and identifies an area for improvement.

Non-obstructive hypertrophic cardiomyopathy exhibit subclinical abnormalities in systolic and diastolic ventricular kinetic energy and systolic haemodynamic forces on 4D flow CMR

Abstract Background Patients with non-obstructive hypertrophic cardiomyopathy (nHCM) exhibit a range of anatomical variations including septal, reverse septal, apical, and concentric hypertrophy. Cardiovascular magnetic resonance imaging (CMR) with 4D flow permits assessment of haemodynamic forces (HDF) and kinetic energy (KE) of intraventricular blood flow (1,2). These parameters may indicate subclinical flow inefficiencies which may not be detectable on routine transthoracic echocardiography (3,4). The aim of this study was therefore to investigate if left ventricular (LV) HDF and KE differ between nHCM and controls, and between subgroups of nHCM. Methods Patients with nHCM (n=71) and age- and sex-matched controls (n=20) underwent CMR at 3T (Trio, Siemens) (Table 1). Patients were categorised as phenotype positive (P+) based on presence of hypertrophy (maximum wall thickness ≥15mm, or ≥13mm with a positive family history), and as phenotype negative (P-) referring to pre-hypertrophic sarcomeric variant carriers. Patients with P+ nHCM were classified into subgroups based on the pattern of hypertrophy. Left ventricular HDF and KE were computed over the cardiac cycle using validated modules (1) (Figure 1). Measurements of HDF were based on the Navier-Stokes equations (1), and analysed in three orthogonal directions as root mean square and peak values for systole and diastole. Force ratio was calculated as the sum of the two transverse components divided by the longitudinal component. The Mann-Whitney U test was used for group comparisons, Pearson analysis for correlations, and Fisher’s exact test for binary categorical data. Results P+, P- patients and controls had comparable LV ejection fraction from CMR, LV outflow tract pressure gradients, and diastolic parameters on echocardiography (Table 1). Systolic HDF and force ratio were increased, primarily in the lateral wall-septum direction in septal and reverse septal P+ patients compared to controls, but did not differ in any other directions in P+ compared to P- patients and to controls (Table 1, Figure 1). Diastolic HDF and force ratio did not differ between groups. Systolic KE was increased in P+ patients compared to P- and to controls (Table 1, Figure 1), mainly through increased KE in patients with septal and reverse septal hypertrophy. P+ patients also had increased late diastolic (A-wave) KE relative to P- patients and to controls (Table 1). Both systolic KE and force ratio correlated with maximum wall thickness in patients (r=0.31, p=0.005; r=0.43, p&amp;lt;0.0001). Conclusion In non-obstructive hypertrophic cardiomyopathy, left ventricular HDF and KE analysis from 4D flow CMR detect subclinical flow abnormalities. Increased systolic HDF and KE are linked to the extent and pattern of hypertrophy. Late diastolic A-wave KE was also abnormal in P+ patients despite normal diastolic velocities on echocardiography.Table 1Figure 1

Speckle tracking echocardiography allows for the detection of subclinical myocardial dysfunction resulting from perfusion abnormalities confirmed by SPECT-based CFR measurement

Abstract Background Speckle tracking echocardiography (STE) is helpful for the detection of subclinical systolic function abnormalities. Coronary flow reserve (CFR) measured by dynamic 99mTc-MIBI SPECT-CZT gamma camera allows the diagnosis of myocardial perfusion defects in patients with suspected coronary artery disease (CAD). Purpose The aim of our study is to assess the diagnostic value of STE and SPECT-based CFR in patients with suspected coronary artery disease (CAD). Methods 85 patients (pts) (37.6% females, mean age 65.4 ± 8.5 years) with suspected CAD underwent 2D and 3D STE, as well as myocardial perfusion study with novel solid-state CZT nuclear camera (dipyridamole stress protocol). We calculated global longitudinal left ventricular strain (GLS), as well as LS of individual coronary artery territories (LAD LS, Cx LS and RCA LS). Total CFR and CFR in three coronary territories were also measured. The presence of CAD (coronary artery stenosis &amp;gt; 70%) was assessed by coronary angiography. Results Significant CAD was confirmed in 50 patients. Mean total CFR (1.71 ± 0.61 vs 2.1 ± 0.52, p = 0.002), as well as CFR in LAD territories (1.54 ± 0.68 vs 1.91 ± 0.56, p = 0.02), RCA territories (1.58 ± 0.82 vs 1.95 ± 0.68, p = 0.048) and Cx territories (1.58 ± 0.78 vs 2.08 ±0.76, p = 0.01) were lower in pts with CAD. In the ROC curve analysis of total CFR for the diagnosis of CAD the AUC was found to be 0.7 (p = 0.001). Mean absolute 2D GLS in pts with total CFR &amp;lt; 2.0 was significantly lower than in pts with CFR &amp;gt;= 2.0 (-14.5 ± 4.3 vs -16.9 ± 3.4, p = 0.005). Similar differences were observed in all three coronary territories (p ≤ 0.05). The same results were not observed in case of 3D GLS . Modest but significant correlations were detected between total CFR and 2D GLS values (r = -0.38; p &amp;lt; 0.001), LAD CFR and 2D LAD LS (r = -0.33; p = 0.002), LCx CFR and 2 D LCx LS (r = -0.39; p &amp;lt; 0.001), total CFR and EF (r = 0.36; p &amp;lt; 0.001). GLS at rest had good diagnostic value for detecting total CFR &amp;lt; 2 (AUC= 0.7; p = 0.004). The criterion with the highest diagnostic accuracy was GLS &amp;gt; (- 18.5) – its sensitivity was 84%, specificity 42%, positive predictive value 0.7, negative predictive value 0.7 and overall accuracy 66%. Conclusions CFR assessed by SPECT provides acceptable diagnostic accuracy for the detection of significant CAD. STE allows for identification of patients with subclinical dysfunction resulting from perfusion abnormalities confirmed by SPECT-based CFR measurement.

Abstract 16723: Comparison of Myocardial Strain During Active Labor in Parturients With Hypertensive Disorders of Pregnancy via Speckle-Tracking Echocardiography

Introduction: Hypertensive disorders of pregnancy (HDP) are increasing in prevalence in the USA and affect maternal morbidity and mortality. Hypothesis: Echocardiographic strain abnormalities may be more prevalent in patients with HDP in active labor, which may unmask subclinical left ventricular dysfunction. Methods: A total of 59 healthy term parturients (≥37 wks gestational age) in active labor (≥6cm cervical dilation) underwent echocardiography to assess cardiac function during peak physiologic stress. Speckle tracking strain analysis was performed using apical 4-, 3- and 2-chamber views during uterine contraction and relaxation with a S5-1 Philips Sparq probe and analyzed with Qlab 9 strain analysis software (Philips, Andover, MA, USA). Abnormal strain cutoff was &gt;-20%. Mean ± SD summarized continuous variables; absolute and relative frequencies for categorical. Welch T-test and Chi-square were used for group comparisons. Results: HDP was present in 21 subjects and absent in 39. Mean age, parity, and prevalence of diabetes did not differ significantly between the two groups. The HDP group had a higher mean BMI (Table 1). The non-HDP group had strain abnormalities in two segments during uterine relaxation, absent during contraction. The HDP group had abnormalities in 5 segments during uterine relaxation, 4 of which were persistently abnormal during uterine contraction (Fig 1). Conclusions: Abnormal strain values were detected at a higher rate in HDP group than in non-HDP group in active labor. Future research is needed to determine if subclinical strain abnormalities in those with HDP during active labor are predictive of developing future cardiovascular disease.

Update on Ultrasound Diagnostic Criteria and New Ultrasound Severity and Activity Scorings of Hidradenitis Suppurativa: Modified SOS-HS and US-HSA.

Hidradenitis suppurativa (HS) is a devasting autoimmune cutaneous disease that affects the hair follicles and can clinically present palpable nodules, abscesses, and tunnels (fistulas), usually in the intertriginous regions. It has been widely reported that color Doppler ultrasound can detect subclinical abnormalities and stage the severity of the disease more accurately. Nevertheless, the ultrasound diagnostic criteria were reported with 15 MHz 10 years ago, and now it is possible to detect early anatomical abnormalities in HS using 70 MHz. Thus, an update of the ultrasonographic diagnostic criteria is needed. The most widely used sonographic staging of severity of HS (SOS-HS) includes the number of affected regions, besides counting the number of key lesions like pseudocysts, fluid collections, and tunnels; however, the total number of affected regions may fit better in an activity scoring. Furthermore, a high number of tunnels or communicated tunnels can complicate the management and may indicate an even more urgent treatment, which should be considered in the severity classification. To date, no hidradenitis scoring of activity has been reported in the literature, making it difficult to track the degree of inflammation under treatment objectively. Therefore, two new scorings are proposed. The first is an updated sonographic scoring of severity called modified SOS-HS (mSOS-HS), and the second is an activity ultrasound scoring of HS called US-HSA. Both staging systems can provide better anatomical information for discriminating the categories and, therefore, selecting more appropriate treatments and supporting research and clinical trials by giving more objective anatomical tools in real-world settings.

Effects of Incretin-Based Treatment on the Diastolic (Dys)Function in Patients with Uncontrolled Type 2 Diabetes Mellitus: A Prospective Study with 1-Year Follow-Up.

Left ventricular diastolic dysfunction (DD) is a subclinical cardiac abnormality in patients with type 2 diabetes mellitus (T2DM) that can progress to heart failure (HF) and increase cardiovascular risk. This prospective study evaluated the DD in T2DM patients without atherosclerotic cardiovascular disease after one year of incretin-based drugs added to standard treatment. Of the 138 enrolled patients (49.30% male, mean age 57.86 ± 8.82, mean T2DM history 5 years), 71 were started on dipeptidyl peptidase-4 inhibitor sitagliptin/saxagliptin, 21 on glucagon-like peptide-1 receptor agonist exenatide, and 46 formed the control group (metformin and sulphonylurea/acarbose). At baseline, 71 patients had grade 1 DD, another 12 had grade 2 and 3 DD, and 15 had indeterminate DD. After one year, DD was evidenced in 50 cases. Diastolic function improved in 9 cases, and 27 patients went from grade 1 to indeterminate DD. The active group benefited more, especially patients treated with exenatide; their metabolic and inflammation profiles also improved the most. An in-depth analysis of echocardiographic parameters and paraclinical results in the context of literature data justifies the conclusion that early assessment of diastolic function in T2DM patients is necessary and the benefits of affordable incretin-based treatment may extend to subclinical cardiovascular manifestations such as DD.

Localized proteomic differences in the choroid plexus of Alzheimer's disease and epilepsy patients.

Alzheimer's disease (AD) and epilepsy are reciprocally related. Among sporadic AD patients, clinical seizures occur in 10-22% and subclinical epileptiform abnormalities occur in 22-54%. Cognitive deficits, especially short-term memory impairments, occur in most epilepsy patients. Common neurophysiological and molecular mechanisms occur in AD and epilepsy. The choroid plexus undergoes pathological changes in aging, AD, and epilepsy, including decreased CSF turnover, amyloid beta (Aβ), and tau accumulation due to impaired clearance and disrupted CSF amino acid homeostasis. This pathology may contribute to synaptic dysfunction in AD and epilepsy. We evaluated control (n = 8), severe AD (n = 8; A3, B3, C3 neuropathology), and epilepsy autopsy cases (n = 12) using laser capture microdissection (LCM) followed by label-free quantitative mass spectrometry on the choroid plexus adjacent to the hippocampus at the lateral geniculate nucleus level. Proteomics identified 2,459 proteins in the choroid plexus. At a 5% false discovery rate (FDR), 616 proteins were differentially expressed in AD vs. control, 1 protein in epilepsy vs. control, and 438 proteins in AD vs. epilepsy. There was more variability in the epilepsy group across syndromes. The top 20 signaling pathways associated with differentially expressed proteins in AD vs. control included cell metabolism pathways; activated fatty acid beta-oxidation (p = 2.00 x 10-7, z = 3.00), and inhibited glycolysis (p = 1.00 x 10-12, z = -3.46). For AD vs. epilepsy, the altered pathways included cell metabolism pathways, activated complement system (p = 5.62 x 10-5, z = 2.00), and pathogen-induced cytokine storm (p = 2.19 x 10-2, z = 3.61). Of the 617 altered proteins in AD and epilepsy vs. controls, 497 (81%) were positively correlated (p < 0.0001, R2 = 0.27). We found altered signaling pathways in the choroid plexus of severe AD cases and many correlated changes in the protein expression of cell metabolism pathways in AD and epilepsy cases. The shared molecular mechanisms should be investigated further to distinguish primary pathogenic changes from the secondary ones. These mechanisms could inform novel therapeutic strategies to prevent disease progression or restore normal function. A focus on dual-diagnosed AD/epilepsy cases, specific epilepsy syndromes, such as temporal lobe epilepsy, and changes across different severity levels in AD and epilepsy would add to our understanding.

Subclinical microvascular changes in ANCA-vasculitides: the role of optical coherence tomography angiography and nailfold capillaroscopy in the detection of disease-related damage

BackgroundBoth cardiovascular and complement-mediated disorders might lead to microvascular damages in anti-neutrophil cytoplasm autoantibodies (ANCA)-associated vasculitides (AAV). We aimed at investigating, for the first time, subclinical microvascular abnormalities with non-invasive techniques in AAV patients by analyzing both retinal and nailfold capillary changes. Retinal plexi were investigated using optical coherence tomography angiography (OCT-A), while nailfold capillary changes by video-capillaroscopy (NVC). Potential correlations between microvessels’ abnormalities and disease damage were also explored.MethodsAn observational study was conducted on consecutive patients who met the inclusion criteria of defined diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA), granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA), age ≥ 18 ≤ 75 yrs, and no ophthalmological disorders. Disease activity was assessed by Birmingham Vasculitis Activity Score (BVAS), damage by Vasculitis Damage Index (VDI), and poorer prognosis by the Five Factor Score (FFS). Quantitative analysis of vessel density (VD) was performed by OCT-A in both superficial and deep capillary plexi. Figures and detailed analysis from NVC were performed for all subjects in the study.ResultsIncluded AAV patients (n = 23) were compared with 20 age/sex-matched healthy controls (HC). Retinal VD in superficial whole and parafoveal plexi resulted significantly decreased in AAV compared to HC (P = 0.02 and P = 0.01, respectively). Furthermore, deep whole and parafoveal vessel density was strongly reduced in AAV than HC (P ≤ 0.0001 for both). In AAV patients, significant inverse correlations occurred between VDI and OCTA-VD in both superficial (parafoveal, P = 0.03) and deep plexi (whole, P = 0.003, and parafoveal P = 0.02). Non-specific NVC pattern abnormalities occurred in 82% of AAV patients with a similar prevalence (75%) in HC. In AAV, common abnormalities were edema and tortuosity in a comparable distribution with HC. Correlations between NVC changes and OCT-A abnormalities have not been described.ConclusionSubclinical microvascular retinal changes occur in patients with AAV and correlate with the disease-related damage. In this context, the OCT-A can represent a useful tool in the early detection of vascular damage. AAV patients present microvascular abnormalities at NVC, whose clinical relevance requires further studies.

Is increased myocardial triglyceride content associated with early changes in left ventricular function? A 1H-MRS and MRI strain study.

Type 2 diabetes (T2D) and obesity induce left ventricular (LV) dysfunction. The underlying pathophysiological mechanisms remain unclear, but myocardial triglyceride content (MTGC) could be involved. This study aimed to determine which clinical and biological factors are associated with increased MTGC and to establish whether MTGC is associated with early changes in LV function. A retrospective study was conducted using five previous prospective cohorts, leading to 338 subjects studied, including 208 well-phenotyped healthy volunteers and 130 subjects living with T2D and/or obesity. All the subjects underwent proton magnetic resonance spectroscopy and feature tracking cardiac magnetic resonance imaging to measure myocardial strain. MTGC content increased with age, body mass index (BMI), waist circumference, T2D, obesity, hypertension, and dyslipidemia, but the only independent correlate found in multivariate analysis was BMI (p=0.01; R²=0.20). MTGC was correlated to LV diastolic dysfunction, notably with the global peak early diastolic circumferential strain rate (r=-0.17, p=0.003), the global peak late diastolic circumferential strain rate (r=0.40, p<0.0001) and global peak late diastolic longitudinal strain rate (r=0.24, p<0.0001). MTGC was also correlated to systolic dysfunction via end-systolic volume index (r=-0.34, p<0.0001) and stroke volume index (r=-0.31, p<0.0001), but not with longitudinal strain (r=0.009, p=0.88). Interestingly, the associations between MTGC and strain measures did not persist in multivariate analysis. Furthermore, MTGC was independently associated with LV end-systolic volume index (p=0.01, R²=0.29), LV end-diastolic volume index (p=0.04, R²=0.46), and LV mass (p=0.002, R²=0.58). Predicting MTGC remains a challenge in routine clinical practice, as only BMI independently correlates with increased MTGC. MTGC may play a role in LV dysfunction but does not appear to be involved in the development of subclinical strain abnormalities.

Subclinical retinopathy in systemic lupus erythematosus patients - optical coherence tomography study.

The aim was to detect subclinical structural retinal abnormalities in optical coherence tomography (OCT) in ophthalmologically asymptomatic systemic lupus erythematosus (SLE) patients without signs of lupus retinopathy or drug toxicity in fundus examination and in OCT and to assess the relationship between OCT parameters and disease activity, therapy type and burden on other organs to demonstrate the utility of OCT in early retinal impairment in SLE patients. Cross-sectional study. Thirty-three SLE patients (57 eyes) and 31 healthy individuals (56 eyes) were enrolled in the study. We excluded patients with evidence of lupus retinopathy or hydroxychloroquine (HCQ) toxicity on OCT or fundus examination to reveal any subclinical changes. All patients underwent full ophthalmologic examination in the slit lamp including best corrected visual acuity, tonometry, and OCT. The Kolmogorov-Smirnov distribution test was used to assess the normal distribution in quantitative values. The differences between the individual measured parameters in the groups were analyzed using the Mann-Whitney U test. Spearman's rank correlation test was used to assess the correlation between the measured parameters and quantitative clinical data. There was no difference in the OCT findings between SLE and healthy control groups. Among the study group a negative correlation was found between disease duration and age and retinal nerve fiber layer thickness in the inferior quadrant (p = 0.0063, p = 0.0036). No correlations were observed between examined retinal parameters and duration of hydroxychloroquine therapy, hydroxychloroquine as well as chloroquine cumulative dose and disease activity indices. Optical coherence tomography is a widespread ophthalmic modality used for SLE retinopathy and HCQ toxicity screening. Our study did not demonstrate its clinical potency in diagnosis of subclinical retinal involvement. An optical coherence tomography device seems to be less sensitive in subclinical retinal impairment detection than optical coherence tomography angiography.

CLINICAL AND ECHOCARDIOGRAPHIC DIVERSITY ASSOCIATED WITH PHYSICAL FITNESS: THE PROJECT BASELINE HEALTH STUDY

Objective: Risk factors and subclinical changes in cardiac structure or function may indicate the development of heart failure (HF). However, different HF risk factors and echocardiographic phenotypes may be associated with different risk for HF progression. In community-dwelling individuals, we determined the heterogeneity in risk factor and echocardiographic profiles and assessed its association with physical performance metrics. Design and method: 2036 participants (50.4 ± 17.0 years, 56.2% women, 37.8% hypertensive) without symptomatic HF underwent echocardiography and physical performance testing including 6-minute walk (6MWT) and treadmill exercise test. Echocardiographic profiles of left and right heart remodeling and dysfunction were defined using sex-specific internal reference values. The cohort was subdivided based on presence (+) or absence (-) of HF risk factors and echocardiographic abnormalities (Echo-/RF-, Echo-/RF+, Echo+/RF-, Echo+/RF+). Participants in Echo+/RF+ were stratified according to the most severe echocardiographic abnormality present (reduced ejection fraction (EF), left ventricular (LV) hypertrophy/diastolic dysfunction or other echo abnormalities). Associations between Echo/RF subgroups and physical performance metrics were assessed. Results: Prevalence was: 35.3% for Echo-/RF-, 39.3% for Echo-/RF+, 4.7% for Echo+/RF- and 20.6% for Echo+/RF+. Between the individuals with echocardiographic abnormalities (Echo+), we observed a large diversity in echocardiographic profiles. Yet, participants with echocardiographic abnormalities but no HF risk factors (Echo+/RF-, 18.6% of Echo+) predominantly had echo abnormalities other than LV diastolic dysfunction, hypertrophy and reduced EF, while their physical performance was similar to people with normal echocardiography without HF risk factors (Echo-/RF-). In contrast, Echo+ participants with risk factors (Echo+/RF+) were characterized by LV diastolic dysfunction, hypertrophy or reduced EF, which all related to lower 6MWT distance and lower exercise capacity (Figure panel A). The presence of both HF risk factors and LV dysfunction/hypertrophy was associated with worst physical performance. Conclusions: Subclinical echocardiographic abnormalities suggest HF pathogenesis, but the type of echo abnormality and presence of HF risk factors should be considered to distinguish adverse changes from adaptive (benign) remodeling and further stratify HF risk. Concomitant presence of risk factors and LV dysfunction/hypertrophy may identify individuals with poor exercise capacity and thus at high risk for progression towards overt HF (Figure panel B).

Assessment of subclinical cardiac dysfunction by speckle-tracking echocardiography among people living with human immunodeficiency virus.

People living with HIV (PLWH) have an increased risk of developing cardiovascular diseases (CVD). As speckle-tracking echocardiography (STE) has been used to detect subclinical myocardial abnormalities, this study aims to detect early cardiac impairment among Asian PLWH using STE and to investigate the associated risk factors. We consecutively recruited asymptomatic PLWH without previous CVD from a medical center of Taiwan, and their cardiac function was evaluated by conventional echocardiogram and STE. Enrolled PLWH were classified as antiretroviral therapy (ART)-experienced and ART-naive, and multivariable regressions were used to assess the association between myocardial strain and risk factors including traditional CVD and HIV-associated factors. A total of 181 PLWH (mean age: 36.4 ± 11.4 years, 173 males) were recruited and conventional echocardiogram parameters were within normal ranges. Decreased myocardial strain across the myocardium was found, with a mean left ventricular (LV) global longitudinal strain of -18.7 ± 2.9%. The LV strain in the ART-experienced group (-19.0 ± 2.9%) was significantly better than the ART-naive group (-17.9 ± 2.8%), despite a younger age and lesser CVD risk factors in the ART-naive group. Hypertension [B = 1.92, 95% confidence interval (95% CI) 0.19-3.62, p = 0.029] and ART-naive with both low and high viral loads (VL) (B = 1.09, 95% CI 0.03-2.16, p = 0.047; and B = 2.00, 95% CI, 0.22-3.79, p = 0.029) were significantly associated with reduced myocardial strain. This is the first and largest cohort using STE to investigate myocardial strain in Asian PLWH. Our results suggest that hypertension and detectable VL are associated with impaired myocardial strain. Thus, timely ART administration with VL suppression and hypertension control are crucial in preventing CVD when making the management parallel with the improved life expectancy of PLWH on ART.