Diagnostic criteria for eosinophilic chronic rhinosinusitis: Comparative analysis and novel scoring system.

BACKGROUND: Accurate identification of eosinophilic chronic rhinosinusitis is essentialg because its treatment and prognosis substantially differ from other subtypes. METHODS: This retrospective observational study included 640 patients who underwent endoscopic sinus surgery for chronic rhinosinusitis in a single tertiary center from January 2021 to December 2022. Receiver operating characteristic curves were generated to compare accuracy, sensitivity, specificity of the novel scoring system, and previous diagnostic criteria (Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis, European Forum for Research and Education in Allergy and Airway Diseases, European Position Paper on Rhinosinusitis and Nasal Polyps, and Sakuma et al.) for predicting eosinophilic chronic rhinosinusitis (ECRS) by tissue eosinophil count ≥70 per high power field. RESULTS: Patients were randomly divided into estimation (n = 430) and validation (n = 210) groups. The area under the receiver operating characteristic curve for the novel score was 0.753 (95% confidence interval [CI], 0.670-0.835) in the estimation group, 0.729 (0.629-0.830) in the validation group, and 0.661 (0.584-0.738) in the 20-fold cross-validation with the entire dataset. CONCLUSIONS: We propose a novel scoring system that incorporates three key parameters: "novel score = blood eosinophil (%) + total Lund-Mackay score of anterior ethmoid sinuses + 2 if nasal polyp present" greater than 7 can be reliably used for diagnosing ECRS. This system can facilitate decision-making processes regarding the administration of oral steroids and biologics targeting type 2 inflammation prior to surgical intervention.

Hypertrophic cardiomyopathy detection with artificial intelligence electrocardiography in international cohorts: an external validation study.

Aims: Recently, deep learning artificial intelligence (AI) models have been trained to detect cardiovascular conditions, including hypertrophic cardiomyopathy (HCM), from the 12-lead electrocardiogram (ECG). In this external validation study, we sought to assess the performance of an AI-ECG algorithm for detecting HCM in diverse international cohorts. Methods and results: A convolutional neural network-based AI-ECG algorithm was developed previously in a single-centre North American HCM cohort (Mayo Clinic). This algorithm was applied to the raw 12-lead ECG data of patients with HCM and non-HCM controls from three external cohorts (Bern, Switzerland; Oxford, UK; and Seoul, South Korea). The algorithm's ability to distinguish HCM vs. non-HCM status from the ECG alone was examined. A total of 773 patients with HCM and 3867 non-HCM controls were included across three sites in the merged external validation cohort. The HCM study sample comprised 54.6% East Asian, 43.2% White, and 2.2% Black patients. Median AI-ECG probabilities of HCM were 85% for patients with HCM and 0.3% for controls (P < 0.001). Overall, the AI-ECG algorithm had an area under the receiver operating characteristic curve (AUC) of 0.922 [95% confidence interval (CI) 0.910-0.934], with diagnostic accuracy 86.9%, sensitivity 82.8%, and specificity 87.7% for HCM detection. In age- and sex-matched analysis (case-control ratio 1:2), the AUC was 0.921 (95% CI 0.909-0.934) with accuracy 88.5%, sensitivity 82.8%, and specificity 90.4%. Conclusion: The AI-ECG algorithm determined HCM status from the 12-lead ECG with high accuracy in diverse international cohorts, providing evidence for external validity. The value of this algorithm in improving HCM detection in clinical practice and screening settings requires prospective evaluation.

Association of Fibrate use with clinical expression of hypertrophic cardiomyopathy.

AIMS: An association between obesity, metabolic abnormalities and clinical hypertrophic cardiomyopathy (HCM) expression has been reported. We investigated whether managing dyslipidaemia with fibrates could affect the clinical expression of HCM. METHODS: We screened patients who used fibrates between 2010 and 2017 from a nationwide database. After excluding patients with a history of HCM, we identified fibrate-user group (n = 412 823). We then constructed a 1:1 matched cohort of fibrate-naïve participants (n = 412 823). After a 1 year lag period, we identified the incident HCM cases for the following 5 years. RESULTS: During a median follow-up period of 3.96 years, we identified 454 incident clinical HCM cases. After adjusting for covariates, fibrate use was associated with a lower risk of clinical HCM expression [hazard ratio (HR) 95% confidence interval (CI): 0.763 (0.630-0.924)]. In subgroup analyses, fibrate use was associated with a reduced risk of clinical HCM expression in patients with a body mass index ≥25 kg/m2 and those with abdominal obesity [HR (95% CI): 0.719 (0.553-0.934) and 0.655 (0.492-0.872)], but not in those without obesity. Fibrate use was also associated with lower risks of incident clinical HCM in patients with triglyceride levels ≥150 mg/dL and those with metabolic syndrome [HR (95% CI): 0.741 (0.591-0.929) and 0.750 (0.609-0.923)], but not in their counterparts. Regarding lifestyle behaviours, fibrate use appeared to provide more prognostic benefits in patients who currently smoked, consumed alcohol or did not engage in regular physical activities. CONCLUSION: The use of fibrates is associated with a lower incidence of clinical HCM expression. This association was also more prominent in those with obesity, unhealthy metabolic profiles and poor lifestyle behaviours.

Impact of Aeroallergen Sensitization on Chronic Rhinosinusitis.

PURPOSE: This study investigated the impact of aeroallergens on the development and progression of chronic rhinosinusitis (CRS), with a focus on the specific associations between aeroallergens and CRS according to allergen type, number, and extent of sensitization. METHODS: The medical records of 256 CRS patients were retrospectively analyzed. All were divided into nonallergic, house dust mite (HDM)-allergic, pollen-allergic, and double allergic groups via specific immunoglobulin E (IgE) testing. Clinical characteristics, computed tomography (CT) scores, olfactory functions, and demographic data were compared. Correlation analysis was performed to explore the relationships between the extent of allergen sensitization and CRS severity. Binary logistic regression analysis was used to identify risk factors for hyposmia and anosmia. RESULTS: The allergic group exhibited higher total CT scores than the nonallergic group (P = 0.001). Sensitivity to HDM or pollen allergens alone was not significantly associated with increased CRS severity. No significant differences were observed between the effects of HDM and pollen allergens on CRS severity. However, the double allergic group exhibited significantly higher CT scores (P < 0.001, < 0.001, and 0.003) than the other groups. Although the prevalence rates of anosmia and hyposmia were notably higher in the double allergic group, the difference was not statistically significant. The maximum specific IgE levels to HDM and pollen allergens positively correlated with the CT scores (P = 0.001 and 0.001, respectively). CONCLUSIONS: Allergen sensitization, particularly to multiple common allergens, contributed to CRS severity. CRS patients sensitized to both HDM and pollen allergens tended to experience the diminished olfactory function. These findings underscore the importance of considering the allergen sensitization pattern when assessing CRS severity and its potential progression.

Mitral Annular Tissue Velocity Predicts Survival in Patients With Primary Mitral Regurgitation.

BACKGROUND AND OBJECTIVES: Early diastolic mitral annular tissue (e') velocity is a commonly used marker of left ventricular (LV) diastolic function. This study aimed to investigate the prognostic implications of e' velocity in patients with mitral regurgitation (MR). METHODS: This retrospective cohort study included 1,536 consecutive patients aged <65 years with moderate or severe chronic primary MR diagnosed between 2009 and 2018. The primary and secondary outcomes were all-cause and cardiovascular mortality, respectively. According to the current guidelines, the cut-off value of e' velocity was defined as 7 cm/s. RESULTS: A total of 404 individuals were enrolled (median age, 51.0 years; 64.1% male; 47.8% severe MR). During a median 6.0-year follow-up, there were 40 all-cause mortality and 16 cardiovascular deaths. Multivariate analysis revealed a significant association between e' velocity and all-cause death (adjusted hazard ratio [aHR], 0.770; 95% confidence interval [CI], 0.634-0.935; p=0.008) and cardiovascular death (aHR, 0.690; 95% CI, 0.477-0.998; p=0.049). Abnormal e' velocity (≤7 cm/s) independently predicted all-cause death (aHR, 2.467; 95% CI, 1.170-5.200; p=0.018) and cardiovascular death (aHR, 5.021; 95% CI, 1.189-21.211; p=0.028), regardless of symptoms, LV dimension and ejection fraction. Subgroup analysis according to sex, MR severity, mitral valve replacement/repair, and symptoms, showed no significant interactions. Including e' velocity in the 10-year risk score improved reclassification for mortality (net reclassification improvement [NRI], 0.154; 95% CI, 0.308-0.910; p<0.001) and cardiovascular death (NRI, 1.018; 95% CI, 0.680-1.356; p<0.001). CONCLUSIONS: In patients aged <65 years with primary MR, e' velocity served as an independent predictor of all-cause and cardiovascular deaths.

Positional obstructive sleep apnea and periodic limb movement during sleep: A large multi-center study.

Objectives: The relationships among positional obstructive sleep apnea (POSA), obstructive sleep apnea (OSA), and periodic limb movement during sleep (PLMS) are unclear. We analyzed these relationships according to OSA severity and explored the underlying mechanisms. Methods: We retrospectively reviewed 6,140 eligible participants who underwent full-night diagnostic polysomnography in four clinical centers over a period of 5 years with eventsynchronized analysis. The PLMS index (PLMI) and periodic limb movements with arousal index (PLMAI) were evaluated. The effects of POSA on the PLMI, PLMAI, and PLMS were analyzed according to OSA severity. Results: The mean PLMI and PLMAI, as well as PLMS prevalence, were significantly lower in those with severe OSA than in those with mild and moderate OSA. The mean PLMI was higher in mild OSA group than in control group. The mean PLMI (4.80 ± 12.71 vs. 2.59 ± 9.82 events/h, p < 0.001) and PLMAI (0.89 ± 3.66 vs. 0.53 ± 3.33 events/h, p < 0.001), and the prevalence of PLMS (11% vs. 5.3%, p < 0.001) were higher in patients with POSA than patients with non-POSA. This trend was particularly marked in severe OSA group (OR 1.55, 95%CI [1.07-2.27]) and less so in mild (OR 0.56, 95%CI [0.30-1.03]) and moderate (OR 1.82, 95%CI [0.99-3.34]) OSA groups. Conclusion: The POSA group tended to have a higher prevalence of PLMS, particularly in those with severe OSA. If PLMS is prominent, diagnosis and treatment of POSA and OSA may be considered.

Next-Generation Cardiac Interfacing Technologies Using Nanomaterial-Based Soft Bioelectronics.

Cardiac interfacing devices are essential components for the management of cardiovascular diseases, particularly in terms of electrophysiological monitoring and implementation of therapies. However, conventional cardiac devices are typically composed of rigid and bulky materials and thus pose significant challenges for effective long-term interfacing with the curvilinear surface of a dynamically beating heart. In this regard, the recent development of intrinsically soft bioelectronic devices using nanocomposites, which are fabricated by blending conductive nanofillers in polymeric and elastomeric matrices, has shown great promise. The intrinsically soft bioelectronics not only endure the dynamic beating motion of the heart and maintain stable performance but also enable conformal, reliable, and large-area interfacing with the target cardiac tissue, allowing for high-quality electrophysiological mapping, feedback electrical stimulations, and even mechanical assistance. Here, we explore next-generation cardiac interfacing strategies based on soft bioelectronic devices that utilize elastic conductive nanocomposites. We first discuss the conventional cardiac devices used to manage cardiovascular diseases and explain their undesired limitations. Then, we introduce intrinsically soft polymeric materials and mechanical restraint devices utilizing soft polymeric materials. After the discussion of the fabrication and functionalization of conductive nanomaterials, the introduction of intrinsically soft bioelectronics using nanocomposites and their application to cardiac monitoring and feedback therapy follow. Finally, comments on the future prospects of soft bioelectronics for cardiac interfacing technologies are discussed.

Alcohol is neither a risk factor nor a protective factor for sudden cardiac death and/or fatal ventricular arrhythmia: A population-based study with genetic traits and alcohol consumption in the UK Biobank.

BACKGROUND: The association between alcohol consumption and the risk of sudden cardiac death and/or fatal ventricular arrhythmia remains controversial. OBJECTIVE: We analyzed the association between alcohol consumption, genetic traits for alcohol metabolism, and the risk of sudden cardiac death and/or fatal ventricular arrhythmia. METHODS: We identified 397,164 individuals enrolled between 2006 and 2010 from the UK Biobank database and followed them until 2021. Alcohol consumption was categorized as current nondrinkers (nondrinkers and ex-drinkers), mild drinkers, moderate drinkers, or heavy drinkers. Genetic traits of alcohol metabolism were stratified according to the polygenic risk score tertiles. The primary and secondary outcomes were a composite of sudden cardiac death and fatal ventricular arrhythmia as well as their individual components. RESULTS: During follow-up (median 12.5 years), 3543 cases (0.89%) of clinical outcomes occurred. Although mild, moderate, and heavy drinkers showed deceased risks of outcomes compared with current nondrinkers, there was no prognostic difference among nondrinkers, mild drinkers, moderate drinkers, and heavy drinkers. Ex-drinkers showed an increased risk in univariate analysis, but the significance was attenuated after adjusting covariates (hazard ratio 1.19; 95% confidence interval 0.94-1.50). As a continuous variable, alcohol consumption was not associated with clinical outcomes (hazard ratio 1.01; 95% confidence interval 0.99-1.02). Consistent with these findings, there was no association between genetic traits for alcohol metabolism and the risk of clinical outcomes. CONCLUSION: Alcohol consumption was neither a protective factor nor a risk factor for sudden cardiac death or fatal ventricular arrhythmia. Genetic traits of alcohol metabolism were not associated with the clinical prognosis.

Erratum: Correction of Figures in the Article "Angiotensin II Type 1 Receptor Blocker, Fimasartan, Reduces Vascular Smooth Muscle Cell Senescence by Inhibiting the CYR61 Signaling Pathway".

This corrects the article on p. 615 in vol. 49, PMID: 31074217.

Mildly Reduced Renal Function Is Associated With Increased Heart Failure Admissions in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: The association between renal dysfunction and cardiovascular outcomes has yet to be determined in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate whether mildly reduced renal function is associated with the prognosis in patients with HCM. METHODS: Patients with HCM were enrolled at two tertiary HCM centers. Patients who were on dialysis, or had a previous history of heart failure (HF) or stroke were excluded. Patients were categorized into 3 groups by estimated glomerular filtration rate (eGFR): stage I (eGFR ≥ 90 mL/min/1.73 m², n = 538), stage II (eGFR 60-89 mL/min/1.73 m², n = 953), and stage III-V (eGFR < 60 mL/min/1.73 m², n = 265). Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, hospitalization for HF (HHF), or stroke during median 4.0-year follow-up. Multivariable Cox regression model was used to adjust for covariates. RESULTS: Among 1,756 HCM patients (mean 61.0 ± 13.4 years; 68.1% men), patients with stage III-V renal function had a significantly higher risk of MACEs (adjusted hazard ratio [aHR], 2.71; 95% confidence interval [CI], 1.39-5.27; P = 0.003), which was largely driven by increased incidence of cardiovascular death and HHF compared to those with stage I renal function. Even in patients with stage II renal function, the risk of MACE (vs. stage I: aHR, 2.21' 95% CI, 1.23-3.96; P = 0.008) and HHF (vs. stage I: aHR, 2.62; 95% CI, 1.23-5.58; P = 0.012) was significantly increased. CONCLUSION: This real-world observation showed that even mildly reduced renal function (i.e., eGFR 60-89 mL/min/1.73 m²) in patients with HCM was associated with an increased risk of MACEs, especially for HHF.

Differing Efficacy of Dapagliflozin Versus Empagliflozin on the Risk of Incident Atrial Fibrillation in Patients With Type 2 Diabetes: A Real-World Observation Using a Nationwide, Population-Based Cohort.

BACKGROUND: Meta-analyses of large clinical trials investigating SGLT2 (sodium-glucose cotransporter-2) inhibitors have suggested their protective effects against atrial fibrillation in patients with type 2 diabetes. However, the results were predominantly driven from trials involving dapagliflozin. METHODS AND RESULTS: We used a nationwide, population-based cohort of patients with type 2 diabetes who initiated either dapagliflozin or empagliflozin between May 2016 and December 2018. An active-comparator, new-user design was used, and the 2 groups of patients were matched using propensity scores. The primary outcome was incident nonvalvular atrial fibrillation, which was analyzed using both the main intention-to-treat and sensitivity analysis that censored patients who skipped their medications for ≥30 days. Men ≥55 years of age and women ≥60 years of age with ≥1 traditional risk factor or those with established cardiovascular disease were categorized as high cardiovascular risk group. Patients not included in the high-risk group were categorized as low risk. After 1:1 propensity-score matching, a total of 137 928 patients (mean age, 55 years; 58% men) were included and followed up for 2.2±0.6 years. The risk of incident atrial fibrillation was significantly lower in the dapagliflozin group in both the main (hazard ratio [HR], 0.885 [95% CI, 0.789-0.992]) and sensitivity analyses (HR, 0.835 [95% CI, 0.719-0.970]). Notably, this was consistent in both the low and high cardiovascular risk groups. There was no effect modification by age, sex, body mass index, duration of diabetes, or renal function. CONCLUSIONS: This real-world, population-based study demonstrates that patients with type 2 diabetes using dapagliflozin may have a lower risk of developing nonvalvular atrial fibrillation than those using empagliflozin.

Risk of newly developed atrial fibrillation by alcohol consumption differs according to genetic predisposition to alcohol metabolism: a large-scale cohort study with UK Biobank.

BACKGROUND: The predictive relationship between mild-to-moderate alcohol consumption and the risk of incident atrial fibrillation (AF) remains controversial. OBJECTIVE: We investigated whether the relationship between alcohol consumption and the risk of incident AF could be associated with the genetic predisposition to alcohol metabolism. METHODS: A total of 399,329 subjects with genetic data from the UK Biobank database, enrolled between 2006 and 2010, were identified and followed for incident AF until 2021. Genetic predisposition to alcohol metabolism was stratified according to the polygenic risk score (PRS) tertiles. Alcohol consumption was categorized as non-drinkers, mild-to-moderate drinkers (< 30 g/day), and heavy drinkers (≥ 30 g/day). RESULTS: During the follow-up (median 12.2 years), 19,237 cases of AF occurred. When stratified by PRS tertiles, there was a significant relationship between genetic predisposition to alcohol metabolism and actual alcohol consumption habits (P < 0.001). Mild-to-moderate drinkers showed a decreased risk of AF (HR 0.96, 95% CI 0.92-0.99), and heavy drinkers showed an increased risk of AF (HR 1.06, 95% CI 1.02-1.10) compared to non-drinkers. When stratified according to PRS tertiles for genetic predisposition to alcohol metabolism, mild-to-moderate drinkers had equivalent AF risks, and heavy drinkers showed increased AF risk in the low PRS tertile group. However, mild-to-moderate drinkers had decreased AF risks and heavy drinkers showed similar risks of AF in the middle/high PRS tertile groups. CONCLUSIONS: Differential associations between alcohol consumption habits and incident AF across genetic predisposition to alcohol metabolism were observed; individuals with genetic predisposition to low alcohol metabolism were more susceptible to AF.