UNASSIGNED: This study aimed to provide an up-to-date evaluation of the burden of alcohol use disorder and its consequences in Iran from 1990 to 2019.
UNASSIGNED: We assessed the burden of alcohol use disorder and its three subsequent disorders, including cirrhosis and other chronic liver diseases, liver cancer, and cardiomyopathy using Global Burden of Disease (GBD) data. We retrieved data on incidence, prevalence, death, Years of Life Lost from mortality (YLL), Years of healthy life Lost due to Disability (YLD), and Disability-Adjusted Life Year (DALY), which is calculated by summing YLL and YLD values, indices, as well as sociodemographic index (SDI) values.
UNASSIGNED: Age-standardized DALY rate of alcohol use disorder reduced from 55.5 in 1990 to 41.8 per 100,000 in 2019 (-24.1 %). Similarly, age-standardized DALY rates of cirrhosis due to alcohol use (-28.7 %), liver cancer due to alcohol use (-20.9 %), and alcoholic cardiomyopathy (-36.3 %) decreased in Iran from 1990 to 2019. In 2019, alcohol use disorder had the highest DALY rate among individuals younger than 55 years, while cirrhosis due to alcohol use imposed the greatest burden on those older than 55. After adjusting for the year, SDI was negatively associated with the age-standardized DALY rate of liver cancer due to alcohol use (p < 0.001), positively associated with that of alcoholic cardiomyopathy (p = 0.002), and not significantly associated with the burden of other conditions (p > 0.05).
UNASSIGNED: Despite reductions in the age-standardized DALY rate of alcohol use disorders and related consequences among Iranians, they remain a serious public health concern in Iran.

Viral myocarditis is a serious complication of viral infections that is known to impact young adults and can result in significant cardiac issues like earlier onset of heart failure, arrhythmia, or structural heart disease if not detected and treated promptly. This is a case report focusing on a 25-year-old woman diagnosed with viral myocarditis highlighting the diagnostic difficulties it can present with due to its diverse symptoms. Following a thorough diagnostic workup and appropriate treatment, including diuretics, antibiotics, and guideline-directed medical therapy, her condition significantly improved. Early suspicion and prompt treatment are important because myocarditis can lead to long-term heart failure. This case shows the nature of the symptoms and the challenges posed by current diagnostic methods. By conducting clinical assessments and using advanced imaging techniques, the diagnosis was confirmed, leading to appropriate treatment for this patient.

Background: The NKX2-5 gene encodes a transcription factor that plays a role in atrioventricular nodal and myocardial development. Pathogenic variants of NKX2-5 are associated with congenital heart disease and sudden cardiac death. The missense variant in this case is one of the more common ones in Northern Europe and has high penetrance in familial cases. To our knowledge, this is the youngest person who died due to this variant. Case summary: This was a healthy, asymptomatic 14-year-old male with well-managed mild congenital dilated cardiomyopathy who died unexpectedly in his home. Postmortem examination revealed the NKX2-5 pathogenic missense variant, p.Phe145Leu, as the only explicable cause of death. Discussion: We propose that immediate family members of those who die suddenly due to NKX2-5 disease undergo genetic counseling and longitudinal screening to include this gene, as pathogenic variants in the NKX2-5 gene may manifest in a time-dependent manner.

UNASSIGNED: Atrial fibrillation/atrial flutter (AF/AFL) are common manifestations of transthyretin amyloid cardiomyopathy (ATTR-CM) but have not been found to be predictive of mortality.
UNASSIGNED: This analysis aimed to examine whether baseline or historical AF/AFL at enrollment was prognostic for all-cause mortality.
UNASSIGNED: In the ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial), a 30-month study of tafamidis vs placebo for ATTR-CM, AF/AFL was evaluated as an independent prognostic factor for all-cause mortality using Cox proportional hazards modelling. The impact of AF/AFL on tafamidis efficacy was explored by adding an interaction term for AF/AFL status and treatment.
UNASSIGNED: ATTR-ACT enrolled 441 patients with ATTR-CM (median age 75 years; 90% male); 314 (71.2%) had baseline or historical AF/AFL at enrollment. AF/AFL was an independent prognostic factor for all-cause mortality after adjusting for covariates prespecified in the ATTR-ACT model (treatment, genotype, New York Heart Association functional class; HR: 0.550; 95% CI: 0.368-0.821) but not in an expanded stepwise model selection analysis including 23 covariates (blood urea nitrogen and N-terminal pro-B-type natriuretic peptide concentration, 6-minute walk test distance, genotype, treatment, and global longitudinal strain were prognostic [P < 0.01]). The interactions between tafamidis treatment and AF/AFL for all-cause mortality (P = 0.33) and changes in Kansas City Cardiomyopathy Questionnaire Overall Summary score (P = 0.83) and 6-minute walk test distance (P = 0.82) were not significant.
UNASSIGNED: In ATTR-ACT, baseline or historical AF/AFL was prognostic for all-cause mortality in analyses with limited adjustment but not after accounting for additional indicators of disease severity. Baseline or historical AF/AFL did not impact the efficacy of tafamidis treatment. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy [ATTR-ACT]; NCT01994889).

UNASSIGNED: Osimertinib is a well-tolerated first- or second-line treatment option for elderly patients with epidermal growth factor receptor mutation-positive advanced non-small cell lung cancer. However, the safety of osimertinib in elderly patients requires further investigation. Herein, we identified safety signals for various osimertinib-related adverse events (AEs) in elderly patients by disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database.
UNASSIGNED: Data from the JADER database from April 2004 to March 2023 were obtained from the Pharmaceuticals and Medical Devices Agency website. Safety signal detection for osimertinib-related AEs in elderly patients (≥70 years old) was determined using the relative elderly reporting odds ratio (ROR). For osimertinib-related AEs, we extracted 92 preferred terms (PTs) and nine standardized MedDRA queries (SMQs).
UNASSIGNED: Safety signals in elderly patients were detected for \"Cardiomyopathy (PT)\" and \"Cardiomyopathy (SMQ)\". The symptoms most frequently associated with \"Cardiomyopathy (SMQ)\" included \"Ejection fraction decreased (PT)\", \"Cardiomyopathy (PT)\", and \"Stress cardiomyopathy (PT)\". Notably, 53.7% of these outcomes were \"Recovery\" or \"Remission\". The median time to the onset of \"Cardiomyopathy (SMQ)\" in elderly patients was 85 days (range=2-537 days).
UNASSIGNED: We demonstrated that patients ≥70 years potentially have increased osimertinib-related cardiomyopathy compared with patients <70 years. In the future, it is necessary to conduct research focusing on cardiomyopathy in elderly patients.

BACKGROUND: Pathogenic variants of MYH7, which encodes the beta-myosin heavy chain protein, are major causes of dilated and hypertrophic cardiomyopathy.
METHODS: In this study, we used whole-genome sequencing data to identify MYH7 variants in 397 patients with various cardiomyopathy subtypes who were participating in the National Project of Bio Big Data pilot study in Korea. We also performed in silico analyses to predict the pathogenicity of the novel variants, comparing them to known pathogenic missense variants.
RESULTS: We identified 27 MYH7 variants in 41 unrelated patients with cardiomyopathy, consisting of 20 previously known pathogenic/likely pathogenic variants, 2 variants of uncertain significance, and 5 novel variants. Notably, the pathogenic variants predominantly clustered within the myosin motor domain of MYH7. We confirmed that the novel identified variants could be pathogenic, as indicated by high prediction scores in the in silico analyses, including SIFT, Mutation Assessor, PROVEAN, PolyPhen-2, CADD, REVEL, MetaLR, MetaRNN, and MetaSVM. Furthermore, we assessed their damaging effects on protein dynamics and stability using DynaMut2 and Missense3D tools.
CONCLUSIONS: Overall, our study identified the distribution of MYH7 variants among patients with cardiomyopathy in Korea, offering new insights for improved diagnosis by enriching the data on the pathogenicity of novel variants using in silico tools and evaluating the function and structural stability of the MYH7 protein.

Haemodynamic forces (HDFs), which represent the forces exchanged between blood and surrounding tissues, are critical in regulating the structure and function of the left ventricle (LV). These forces can be assessed on cardiac magnetic resonance or transthoracic echocardiography exams using specialized software, offering a non-invasive alternative for measuring intraventricular pressure gradients. The analysis of HDFs can be a valuable tool in improving our understanding of cardiovascular disease and providing insights beyond traditional diagnostic and therapeutic approaches. For instance, HDF analysis has the potential to identify early signs of adverse remodelling and cardiac dysfunction, which may not be detected by standard imaging methods such as bidimensional or speckle-tracking echocardiography. This review aims to summarize the principles of HDF analysis and to reappraise its possible applications to cardiac disorders.

The cardiac troponin complex (cTn) is a regulatory component of sarcomere. cTn consists of three subunits: cardiac troponin C (cTnC), which confers Ca2+ sensitivity to muscle; cTnI, which inhibits the interaction of cross-bridge of myosin with thin filament during diastole; and cTnT, which has multiple roles in sarcomere, such as promoting the link between the cTnI-cTnC complex and tropomyosin within the thin filament and influencing Ca2+ sensitivity of cTn and force development during contraction. Conditions that interfere with interactions within cTn and/or other thin filament proteins can be key factors in the regulation of cardiac contraction. These conditions include alterations in myofilament Ca2+ sensitivity, direct changes in cTn function, and triggering downstream events that lead to adverse cardiac remodeling and impairment of heart function. This review describes gene expression and post-translational modifications of cTn as well as the conditions that can adversely affect the delicate balance among the components of cTn, thereby promoting contractile dysfunction.

UNASSIGNED: Black patients have disproportionately more cases of peripartum cardiomyopathy (PPCM) and more severe disease. To better understand these disparities, we examined the geographic distribution of patients with PPCM by race and evaluated associations between race and social vulnerability. We hypothesized that Black patients with PPCM are more likely than White patients to live in socially vulnerable communities.
UNASSIGNED: A retrospective cohort study of patients with PPCM defined by the National Institutes of Health, National Heart, Lung, and Blood Institute was conducted at a single center from January 2000 to November 2017. The US census tract for each patient was identified, and social vulnerability was assessed using the Centers for Disease Control and Prevention Social Vulnerability Index (SVI). Higher SVI values represent a more vulnerable community. SVI and select subcomponents were compared by self-reported race.
UNASSIGNED: Among 90 patients with PPCM (47 White, 43 Black), the ejection fraction at diagnosis was similar between groups, although Black patients were more likely to have an ejection fraction of ≤40% at 6 to 12 months postpartum. Black race was associated with living in areas of greater social vulnerability; mean SVI was significantly higher among Black individuals than among White individuals (.56 versus .33, P=.0003). Black patients lived in areas with more people living in poverty, higher unemployment, and more single-parent households.
UNASSIGNED: Black patients with PPCM were more likely to have persistent left ventricular dysfunction and live in areas of greater social vulnerability. Strategies to achieve equitable social determinants of health are needed to improve health outcomes in Black patients with PPCM.

Treatment of fatty acid oxidation disorders is based on dietary, pharmacological and metabolic decompensation measures. It is essential to provide the patient with sufficient glucose to prevent lipolysis and to avoid the use of fatty acids as fuel as far as possible. Dietary management consists of preventing periods of fasting and restricting fat intake by increasing carbohydrate intake, while maintaining an adequate and uninterrupted caloric intake. In long-chain deficits, long-chain triglyceride restriction should be 10% of total energy, with linoleic acid and linolenic acid intake of 3-4% and 0.5-1% (5/1-10/1 ratio), with medium-chain triglyceride supplementation at 10-25% of total energy (total MCT+LCT ratio = 20-35%). Trihepatnoin is a new therapeutic option with a good safety and efficacy profile. Patients at risk of rhabdomyolysis should ingest MCT or carbohydrates or a combination of both 20 min before exercise. In medium- and short-chain deficits, dietary modifications are not advised (except during exacerbations), with MCT contraindicated and slow sugars recommended 20 min before any significant physical exertion. Parents should be alerted to the need to increase the amount and frequency of carbohydrate intake in stressful situations. The main measure in emergency hospital treatment is the administration of IV glucose. The use of carnitine remains controversial and new therapeutic options are under investigation.