Tehran University of Medical Sciences The Research in Heart Yield and Translational Medicine (RHYTHM) 3115-7270 18 1 2023 01 30 1 9 EN Elaheh Honarkar-Shafie Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. Mohammad Javad Hosseinzadeh-Attar Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. Fatemeh Taheri Department of Clinical Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran. Najme-Sadat Moosavi Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. Mehdi Yaseri Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Mohammad Alidoosti Department of Cardiology, Tehran Heart Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Ali Vasheghani-Farahani Cardiac Primary Prevention Research Center, Cardiovascular Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran. 2022 11 21 2023 01 01 Background: Insulin resistance (IR), even in its subclinical state, is a significant risk factor for the onset and progression of coronary artery disease (CAD). IR is a multifactorial condition, and dietary composition is a factor associated with its development. Elevated advanced glycation end products (AGEs) in the body, secondary to highly processed food consumption, can impair glucose metabolism. The present study investigated whether a restricted AGE diet could affect insulin sensitivity and anthropometric indices reflecting visceral adipose tissue in nondiabetic CAD patients. Methods: This trial randomly allocated 42 angioplasty-treated patients to follow either low-AGE or control diets based on the AHA/NCEP guidelines for 12 weeks. Serum levels of total AGEs, insulin, HbA1c, and fasting blood sugar, as well as anthropometric measurements, were evaluated before and after the intervention. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and anthropometric indices were calculated according to the proposed formula. The patients’ health status was assessed using the Seattle Angina Questionnaire (SAQ) at baseline and after the intervention. Results: Our study showed a significant reduction in anthropometric indices in the low-AGE group after 12 weeks. Insulin levels and IR decreased during the low-AGE diet. No significant changes were observed in the other serum biochemical markers. All SAQ domains significantly decreased in both groups, except for Treatment Satisfaction. Conclusion: A low-AGE diet for 12 weeks had beneficial effects on HOMA-IR and insulin levels in patients with CAD. Regarding the fundamental role of AGE in IR development and body fat distribution, AGE restriction may positively affect these patients. https://rhythm.tums.ac.ir/index.php/jthc/article/view/1759 https://rhythm.tums.ac.ir/index.php/jthc/article/download/1759/1044

Tehran University of Medical Sciences The Research in Heart Yield and Translational Medicine (RHYTHM) 3115-7270 18 1 2023 01 30 10 15 Zahra Momayez Sanat Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Seyyed Mojtaba Ghorashi * Department of MPH, Shiraz School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. **Cardiac Primary Prevention Research Center, Cardiovascular Disease Research Institute, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. Ava Ajir igestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran. Amir Fazeli Cardiac Primary Prevention Research Center, Cardiovascular Disease Research Institute, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. Hamidreza Hekmat Department of Cardiology, Ziaeian Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Negar Omidi Cardiac Primary Prevention Research Center, Cardiovascular Disease Research Institute, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. 2021 11 29 2022 12 01 Background: Coronary artery disease (CAD) and nonalcoholic fatty liver disease (NAFLD) are 2 common diseases around the globe. This investigation aimed to evaluate NAFLD prevalence in patients with CAD and the potential association between NAFLD and CAD. Methods: This case-control study was performed between January 2017 and January 2018 at Ziaeian Hospital, Tehran, Iran. All patients aged between 35 and 5 years and referred for myocardial perfusion imaging were selected for the study. Totally, 180 participants were divided into CAD+ and CAD− groups. CAD was defined as stenosis of greater than 50.0% in at least 1 coronary artery. Afterward, all the patients underwent abdominal sonography and laboratory tests for NAFLD evaluation. Patients with a history of liver diseases, alcohol consumption, and drug-induced steatosis were excluded. Results: The study population consisted of 122 women (67.8%) and 58 men (32.2%) at a mean age of 49.31±5.42 years. NAFLD was detected in 115 patients. NAFLD prevalence in the CAD+ group was 78.9%. NAFLD was determined as an independent risk factor for CAD (OR, 3.9). Conclusion: NAFLD prevalence was high in the CAD+ group. The incidence of steatosis is on the rise in the general population. Hence, considering the high prevalence of abdominal obesity, all patients with NAFLD should be evaluated for CAD.  https://rhythm.tums.ac.ir/index.php/jthc/article/view/1561 https://rhythm.tums.ac.ir/index.php/jthc/article/download/1561/1047

Tehran University of Medical Sciences The Research in Heart Yield and Translational Medicine (RHYTHM) 3115-7270 18 1 2023 01 30 16 23 Hossein Sheibani Clinical Research Development Unit, Imam Hossein Hospital, Shahroud University of Medical Sciences, Shahroud, Iran. Mehran Gheshlaghi Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran. Somayeh Shah Hosseini Imam Hossein Center for Education, Research and Treatment, Shahroud University of Medical Sciences, Shahroud, Iran. Mojgan Javedani Masroor Shahid Akbar Abadi Clinical Research Development Unit (ShACRDU), Iran University of Medical Sciences (IUMS), Tehran, Iran. Salman Daliri Clinical Research Development Unit, Imam Hossein Hospital, Shahroud University of Medical Sciences, Shahroud, Iran. 2022 02 07 2023 03 11 Background: COVID-19 has rapidly become a global health emergency. This infection can cause damage to various organs. Injury to myocardial cells is one of the salient manifestations of COVID-19. The clinical course and outcome of acute coronary syndrome (ACS) are influenced by various factors, including comorbidities and concomitant diseases. One of these acute concomitant diseases is COVID-19, which can affect the clinical course and outcome of acute myocardial infarction (MI). Methods: The present cross-sectional study compared the clinical course and outcome of MI and some of its practical factors between patients with and without COVID-19. The study population consisted of 180 patients (129 males and 51 females) diagnosed with acute MI. Eighty patients had COVID-19 infection concurrently. Results: The mean age of the patients was 65.62 years. The frequencies of non–ST-elevation MI (vs ST-elevation MI), lower ejection fractions (<30), and arrhythmias were significantly higher in the COVID-19 group than in the non–COVID-19 group (P=0.006, 0.003, and P<0.001, respectively). The single-vessel disease was the most frequent angiographic result in the COVID-19 group, while the double-vessel disease was the most frequent angiographic result in the non–COVID-19 group (P<0.001). Conclusion: It appears that patients with ACS who are co-infected with COVID-19 infection need essential care. https://rhythm.tums.ac.ir/index.php/jthc/article/view/1614 https://rhythm.tums.ac.ir/index.php/jthc/article/download/1614/1045

Tehran University of Medical Sciences The Research in Heart Yield and Translational Medicine (RHYTHM) 3115-7270 18 1 2023 01 30 24 32 EN Seyyed Mojtaba Ghorashi 1. MPH Department, Shiraz School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. 2. Cardiovascular Disease Research Institute, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. Pooria Ahmadi 2. Cardiovascular Disease Research Institute, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. Reza Shahnazar Nezhad Khalesi 2. Cardiovascular Disease Research Institute, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. Amir Fazeli 2. Cardiovascular Disease Research Institute, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. Hossein Molavi Vardanjani 1. MPH Department, Shiraz School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Alireza Salehi 1. MPH Department, Shiraz School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Negar Omidi 2. Cardiovascular Disease Research Institute, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. Mesbah Shams 3. Endocrine and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Amirhossein Babaei 4. Otolaryngology Research Center, Department of Otolaryngology, Shiraz University of Medical Sciences, Shiraz, Iran. 5. Student research committee, Shiraz University of Medical Sciences, Shiraz, Iran. 2022 07 21 2022 11 07 Background: While the traditional risk factors of atherosclerotic cardiovascular disease (ASCVD) have been well-established, the evolving role of nontraditional risk factors is not apparent. This study aimed to evaluate the association between nontraditional risk factors and the calculated 10-year ASCVD risk in a general population. Methods: This cross-sectional study was conducted using the Pars Cohort Study data. All inhabitants of the Valashahr district in southern Iran, aged 40–75 years, were invited (2012-2014). Patients with a history of cardiovascular disease (CVD) were excluded. The demographic and lifestyle data were collected using a validated questionnaire. Multinomial logistic regression analysis was used to evaluate the association between the calculated 10-year ASCVD risk and the nontraditional risk factors of CVD, including marital status, ethnicity, educational level, tobacco and opiate consumption, physical inactivity, and psychiatric disorders. Results: Of 9264 participants (mean age =52.2±9.0 y; 45.8% male), 7152 patients met the inclusion criteria. In total, 20.2%, 7.6%, 36.3%, 56.4%, and 46.2% of the population were cigarette smokers, opiate consumers, tobacco consumers, ethnically Fars, and illiterate, respectively. The prevalence rates of low, borderline, and intermediate-to-high 10-year ASCVD risks were 74.3%, 9.8%, and 16.2%, respectively. In multinomial regression, anxiety (adjusted odds ratio [aOR], 0.58; P<0.001) was significantly associated with a lower ASCVD risk, whereas opiate consumption (aOR, 2.94; P<0.001) and illiteracy (aOR, 2.48; P<0.001) were significantly associated with a higher ASCVD risk. Conclusion: Nontraditional risk factors are associated with the 10-year ASCVD risk and, thus, might be considered besides traditional ones for ASCVD in preventive medicine and health policies. https://rhythm.tums.ac.ir/index.php/jthc/article/view/1685 https://rhythm.tums.ac.ir/index.php/jthc/article/download/1685/1046

Tehran University of Medical Sciences The Research in Heart Yield and Translational Medicine (RHYTHM) 3115-7270 18 1 2023 01 30 33 38 EN Maryam Farokhipour Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Farzaneh Ketabchi Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. 2022 09 08 2023 02 01 Background: Heart rate variability (HRV) is calculated by electrocardiography (ECG-HRV) or blood pressure (BP-HRV). The purpose of this study was to determine the validity of the above methods in rats with normal and ischemic hearts during the baroreflex maneuver. Methods: The study was conducted at Shiraz University of Medical Sciences, Shiraz, Iran, in 2021. Sprague-Dawley rats were divided into a sham group and an isoproterenol-mediated cardiac ischemia (ISO) group. Saline and isoproterenol (150 mg/kg) injected subcutaneously for 2 consecutive days in the sham and ISO groups, respectively. Then, the animals were anesthetized with an intraperitoneal injection of sodium thiopental (60 mg/kg), and the femoral artery and vein were cannulated. Baroreflex was activated using an intravenous injection of phenylephrine (10 µg/100 µL saline). ECG, BP, and heart rate (HR) were recorded, and the time domain of HRV and baroreflex gain were calculated. Results: Baroreflex gain in the ISO group (male, weight=275.8±2.8 g, n=8) was lower than that in the sham group (male, weight=258±2.3 g, n=8) (P<0.05). ECG-HRV indicated an increase in the standard deviation of the RR interval (SDRR), the index of overall HRV, and the parasympathetic index of the root mean square of successive differences (RMSSD) in both groups. However, the rise in SDRR and RMSSD in the ISO group was less than that in the sham group (P<0.05). SDRR and RMSSD obtained from BP did not show a difference between the sham and ISO groups, nor did they correspond with the results seen in baroreflex gain. Conclusion: BP-HRV was not as valuable as ECG-HRV in assessing cardiac ischemia. https://rhythm.tums.ac.ir/index.php/jthc/article/view/1716 https://rhythm.tums.ac.ir/index.php/jthc/article/download/1716/1048

Tehran University of Medical Sciences The Research in Heart Yield and Translational Medicine (RHYTHM) 3115-7270 18 1 2023 01 30 39 45 Sedigheh Sadat Naimi Physiotherapy Research Center, School of Rehabilitation, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Soulmaz Rahbar Department of Physiotherapy, School of Rehabilitation Sciences, Hamadan University of Medical Sciences, Hamadan, Iran. Mohammad Reza Asadi Department of Physiotherapy, School of Rehabilitation Sciences, Hamadan University of Medical Sciences, Hamadan, Iran. Hojjat Radinmehr Department of Physiotherapy, School of Rehabilitation Sciences, Hamadan University of Medical Sciences, Hamadan, Iran. https://rhythm.tums.ac.ir/index.php/jthc/article/view/2377 https://rhythm.tums.ac.ir/index.php/jthc/article/download/2377/1250

Tehran University of Medical Sciences The Research in Heart Yield and Translational Medicine (RHYTHM) 3115-7270 21 1 2024 06 22 111 115 Farnaz Ahmadi Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Raha Parnia Simon Fraser University, Vancouver, British Columbia, Canada Bahamin Astani Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Mohammad-Sadegh Keshmiri Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Shakiba Khodadad Department of Gynecology Oncology, Erfan Hospital, Tehran, Iran Hakimeh Sheikhzadeh Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Zahra Daneshmandi Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Faezeh Ansari Mofid Children’s Hospital, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Mahsa Riahi Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Sima Noorali Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Hannaneh Yousefi-Koma Masih Daneshvari Hospital, Tehran, Iran Babak Sharif-Kashani Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. Shadi Shafaghi Lung Transplantation Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran. 2024 07 04 2024 09 22 Background: Pregnancy in women with pulmonary hypertension (PH) is contraindicated because of high mortality rates associated with physiological changes, particularly in the peripartum and postpartum periods. Termination is recommended early if pregnancy occurs. Consequently, clinical experience with continued pregnancy in patients with PH is scarce. Case Presentation: A 31-year-old woman was diagnosed with multiple bilateral pulmonary and right ventricular hydatid cysts. After surgical and pharmacologic treatments, she developed PH due to pulmonary artery obstruction 8 years later. Because of her condition, she was ineligible for surgery and received medical therapy, including tadalafil, bosentan, and eplerenone. After 3 years, she conceived despite advice to avoid pregnancy. At 37 weeks’ gestation, she underwent successful emergency cesarean delivery because of maternal dyspnea and tachycardia. Conclusion: Prompt treatment and regular follow-up in a tertiary care center using a multidisciplinary approach are crucial for managing pregnant patients with PH. https://rhythm.tums.ac.ir/index.php/jthc/article/view/2118 https://rhythm.tums.ac.ir/index.php/jthc/article/download/2118/1252

Tehran University of Medical Sciences The Research in Heart Yield and Translational Medicine (RHYTHM) 3115-7270 21 1 2026 04 26 20 31 Rizki Hilman Department of Cardiology, Faculty of Medicine, Dr. Zainoel Abidin Hospital, Universitas Syiah Kuala, Banda Aceh, Indonesia Adi Purnawarman Department of Cardiology, Faculty of Medicine, Dr. Zainoel Abidin Hospital, Universitas Syiah Kuala, Banda Aceh, Indonesia Haris Munirwan Department of Cardiology, Faculty of Medicine, Dr. Zainoel Abidin Hospital, Universitas Syiah Kuala, Banda Aceh, Indonesia Muhammad Ridwan Department of Cardiology, Faculty of Medicine, Dr. Zainoel Abidin Hospital, Universitas Syiah Kuala, Banda Aceh, Indonesia Herlina Dimiati Department of Pediatric, Faculty of Medicine, Dr. Zainoel Abidin Hospital, Universitas Syiah Kuala, Banda Aceh, Indonesia 2025 12 26 2026 02 03 Background: Arrhythmia is a common and clinically significant complication during hospitalization for ST-segment elevation myocardial infarction (STEMI). This study aimed to identify factors associated with the occurrence of arrhythmia in the acute phase of STEMI. Methods: This single-center cross-sectional study was conducted among adult patients hospitalized with STEMI. Demographic and clinical variables, including cardiovascular risk factors and disease severity (Killip class, Thrombolysis in Myocardial Infarction [TIMI] score, and Global Registry of Acute Coronary Events [GRACE] score), were obtained from medical records. The primary outcome was in-hospital arrhythmia, defined as documented atrial or ventricular tachyarrhythmia or clinically significant bradyarrhythmia. Factors associated with arrhythmia were assessed using bivariate analyses followed by multivariable logistic regression. Results: This study involved 113 patients, with a mean age of 56.4 (11.1) years. Arrhythmia occurred in 26.5% (30 patients) during hospitalization. In bivariate analyses, arrhythmia was associated with higher Killip class (P<0.001), higher TIMI score (P=0.005), higher GRACE score (P=0.001), lower tricuspid annular plane systolic excursion (P=0.002), elevated serum potassium level (P=0.010), and impaired renal function, reflected by higher urea (P=0.005) and creatinine levels (P = 0.004). After multivariable adjustment, only Killip class remained independently associated with arrhythmia: patients presenting with Killip class I had a significantly lower risk of arrhythmia than those with higher Killip classes (adjusted OR, 0.404; 95% CI, 0.20 to 0.80; P=0.009). Conclusion: In hospitalized patients with STEMI, arrhythmic risk is chiefly driven by early clinical severity. Killip class is a simple bedside predictor of in-hospital arrhythmia and can aid early risk stratification and monitoring. https://rhythm.tums.ac.ir/index.php/jthc/article/view/2417 https://rhythm.tums.ac.ir/index.php/jthc/article/download/2417/1242

Tehran University of Medical Sciences The Research in Heart Yield and Translational Medicine (RHYTHM) 3115-7270 21 1 2026 04 26 32 39 Ali Mirzaei Department of Pharmacology & Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran Maryam Mehrpooya Department of Clinical Pharmacy, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran Akram Ranjbar Department of Pharmacology & Toxicology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran Sajad Naghdi Farshchian Cardiovascular Subspecialty Medical Center, Hamadan University of Medical Sciences, Hamadan, Iran Afsaneh Familmotaghi Farshchian Cardiovascular Subspecialty Medical Center, Hamadan University of Medical Sciences, Hamadan, Iran Seyed Saman Talebi Department of Internal Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran Seyed Kianoosh Hosseini Department of Cardiology, School of Medicine, Farshchian Cardiovascular Subspecialty Medical Center, Hamadan University of Medical Sciences, Hamadan, Iran 2025 07 26 2025 12 16 Background: Ischemic heart disease is the leading cause of death worldwide. Oxidative stress plays a key role in myocardial infarction (MI). Ferroptosis, a type of iron-dependent regulated cell death caused by lipid peroxide accumulation, has been identified as a key mechanism in ischemic injury. This study aimed to investigate the association between oxidative stress and ferroptosis in patients with non–ST-segment-elevation myocardial infarction (NSTEMI). Methods: In this case-control study, 25 patients with NSTEMI and 25 controls were included. In serum samples, cardiac markers (troponin I and CK-MB), oxidative stress biomarkers including lipid peroxidation (LPO), total antioxidant capacity (TAC), total thiol groups (TTG), superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity, and iron and ferritin levels were measured. Results: In patients with NSTEMI, serum levels of cardiac markers (troponin I and CK-MB), LPO, iron, and ferritin were significantly higher than in controls. In contrast, TAC, TTG, and SOD and GPx activities were significantly lower in patients with NSTEMI. Conclusion: This study demonstrated a possible role of oxidative stress in the pathophysiology of NSTEMI. Elevated iron and LPO levels and reduced GPx activity may contribute to cardiac cell death through ferroptosis. https://rhythm.tums.ac.ir/index.php/jthc/article/view/2319 https://rhythm.tums.ac.ir/index.php/jthc/article/download/2319/1243

Tehran University of Medical Sciences The Research in Heart Yield and Translational Medicine (RHYTHM) 3115-7270 21 1 2026 04 26 40 49 Fadhlan Rahman Citra Husada Jember Hospital Suryono Suryono Department of Cardiology and Vascular Medicine, Faculty of Medicine, Jember University, Jember, Indonesia; Dr. Soebandi General Hospital, Jember, Indonesia Aditha Maulana Department of Cardiology and Vascular Medicine, Faculty of Medicine, Jember University, Jember, Indonesia; Dr. Soebandi General Hospital, Jember, Indonesia Pipiet Wulandari Department of Cardiology and Vascular Medicine, Faculty of Medicine, Jember University, Jember, Indonesia; Dr. Soebandi General Hospital, Jember, Indonesia 2025 12 15 2026 02 02 Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with substantial morbidity and mortality. AF occurring in individuals without structural heart disease or conventional risk factors, currently referred to as AF without overt comorbidity, remains poorly understood. Genetic susceptibility is thought to contribute, but the underlying molecular mechanisms are incompletely defined. This study aimed to identify key genes and biological processes associated with AF without overt comorbidity using an in-silico bioinformatics approach. Methods: Genes associated with AF without overt comorbidity were retrieved from the GeneCards database using a knowledge-based, database-driven strategy. Functional enrichment analysis of Gene Ontology biological processes was performed using WebGestalt. Protein-protein interaction (PPI) analysis was conducted using STRING and visualized in Cytoscape. Hub genes were identified exclusively using the Density of Maximum Neighborhood Component (DMNC) algorithm via the CytoHubba plugin. Three-dimensional protein structures of selected hub genes were modeled using SWISS-MODEL and evaluated using PROCHECK for exploratory structural characterization. Results: Eighty-one genes associated with AF without overt comorbidity were identified. PPI analysis demonstrated significant interaction enrichment (P<1.0×10⁻¹⁶), indicating a nonrandom and biologically coherent network. Functional enrichment analysis revealed cardiac muscle cell action potential and cardiac muscle contraction as the most significantly enriched biological processes. Ten hub genes were identified based on DMNC ranking. Among these, GPD1L, SCN1B, SCN4B, and KCNE2 showed central network positions and acceptable stereochemical quality in exploratory structural evaluation. Conclusion: This in silico study identifies candidate genes and biological processes potentially involved in AF without overt comorbidity. The findings are hypothesis generating and warrant further functional and clinical validation. https://rhythm.tums.ac.ir/index.php/jthc/article/view/2407 https://rhythm.tums.ac.ir/index.php/jthc/article/download/2407/1244

Tehran University of Medical Sciences The Research in Heart Yield and Translational Medicine (RHYTHM) 3115-7270 21 1 2026 04 26 50 70 Mohammadsadegh Talebi Kahdouei Fetal and Pediatric Cardiovascular Research Center, Children’s Medical Center, Tehran, Iran, Islamic Republic Of Hosein Ghasempour Fetal and Pediatric Cardiovascular Research Center, Children’s Medical Center, Tehran, Iran, Islamic Republic Of Fatemeh Aghaei Fetal and Pediatric Cardiovascular Research Center, Children’s Medical Center, Tehran, Iran, Islamic Republic Of Elaheh Vafaei Fetal and Pediatric Cardiovascular Research Center, Children’s Medical Center, Tehran, Iran, Islamic Republic Of Behnaz Sohrabi School of Medicine, Isfahan University of Medical Science, Isfahan, Iran, Islamic Republic of Ehsan Aghaei Moghadam Fetal and Pediatric Cardiovascular Research Center, Children’s Medical Center, Tehran, Iran, Islamic Republic Of Negin Rahimidanesh School of Medicine, Islamic Azad University, Tehran Medical Branch, Tehran, Iran, Islamic Republic of, Ali Dahmarde Ei Department of General Surgery, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran, Islamic Republic of Mojtaba Shurmij Department of General Surgery, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran, Islamic Republic of 2025 11 17 2026 01 11 Background: Rheumatic heart disease (RHD) remains a major cause of preventable cardiovascular morbidity and mortality, particularly in low- and middle-income countries. Despite the World Health Organization’s 2018 resolution calling for global elimination of RHD, substantial disparities in disease burden persist across regions and levels of socio-economic development. While previous studies have reported global trends, a clear comparative assessment of long-term changes in both fatal and non-fatal RHD burden across socio-demographic and geographic regions remains limited. This study aimed to assess long-term changes in the global burden of RHD between 1990 and 2021, with a specific focus on regional and socio-demographic disparities, using the most recent estimates from the Global Burden of Disease (GBD) 2021 study. We additionally assessed temporal trends across Socio-demographic Index (SDI) groups and GBD regions, with a specific focus on fatal (YLL) and non-fatal (YLD) components of disease burden. Methods: We conducted a secondary analysis of model-based estimates from the Global Burden of Disease (GBD) 2021 study to assess the burden of RHD between 1990 and 2021. Metrics included age-standardized and all-age incidence, prevalence, mortality, years of life lost (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY). Data were stratified by five Socio-demographic Index (SDI) levels and 13 global regions. Estimates were produced using DisMod-MR 2.1 and CODEm and are reported as means with 95% uncertainty intervals (UIs). Results: Globally, age-standardized mortality and DALY rates for RHD declined by 56% and 53%, respectively, from 1990 to 2021. YLL decreased by 59%, while YLD rose by 11%, indicating a shift toward chronic non-fatal burden. For instance, the global age-standardized mortality rate fell from 9.1 (95% UI: 8.4–9.8) to 4.0 (3.6–4.5) per 100,000. High and high-middle SDI regions achieved the greatest reductions across all indicators. In contrast, low and low-middle-SDI regions experienced persistently high absolute deaths and DALYs, with South Asia alone accounting for over 27% of global RHD deaths in 2021. Females consistently bore a higher non-fatal burden (YLD) than males. Although the dataset includes the COVID-19 era, the specific impacts of the pandemic on RHD care and outcomes warrant further investigation. Across all SDI groups and regions, declines in DALYs were largely driven by reductions in years of life lost (YLLs), whereas years lived with disability (YLDs) remained relatively stable. Conclusions: While global RHD mortality has declined, substantial regional and socioeconomic disparities persist. The epidemiologic transition towards disability highlights the need for long-term care infr