Perioperative Opioid Exposure in Adolescents and Long-Term Psychiatric/Utilization Outcomes: A Propensity-Matched Real World Cohort Study.

Cardiomyopathies are a heterogeneous group of myocardial disorders characterized by structural and functional abnormalities of the heart muscle, often leading to mechanical dysfunction, electrical instability, or both. According to their predominant phenotype, cardiomyopathies are commonly classified as hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), dilated cardiomyopathy (DCM), and arrhythmogenic cardiomyopathy (ACM) [,,]. Among these conditions, DCM is one of the most common forms of non-ischemic cardiomyopathy and is defined by left ventricular, or biventricular, dilation associated with systolic dysfunction in the absence of abnormal loading conditions or significant coronary artery disease [,]. DCM represents a major cause of heart failure, arrhythmias, cardiac transplantation, and premature mortality worldwide []. The annual incidence in Europe and North America ranges from 5 to 7.9 cases per 100,000 people []. Other epidemiological studies have consistently reported a higher prevalence and greater severity of DCM in males than in females, with an estimated male-to-female ratio of approximately 2:1. The biological mechanisms underlying these sex-related differences remain incompletely understood and may involve genetic, epigenetic, hormonal, and environmental factors, as well as differences in disease penetrance and expressivity [,]. DCM can be classified into genetic, either familial or sporadic, and acquired forms. Secondary forms may result from ischemic injury, myocarditis, exposure to cardiotoxic agents, metabolic disorders, or endocrine abnormalities [,]. Over the last two decades, advances in next-generation sequencing (NGS) technologies have substantially improved our understanding of the genetic basis of DCM, revealing marked genetic heterogeneity and identifying numerous disease-associated genes [,]. Genetic testing is increasingly recognized as an essential component of clinical evaluation, as it can provide valuable information for diagnosis, prognosis, family screening, and personalized management strategies [,]. Among the genes most frequently implicated in DCM, TTN has attracted particular attention. This gene encodes titin, the largest known human protein and a critical structural component of the sarcomere. Multiple studies have shown that pathogenic TTN variants, particularly truncating variants, represent the most common genetic cause of DCM [,,]. A meta-analysis published in 2019 estimated that TTN variants account for approximately 17% of DCM cases, underscoring their major contribution to disease pathogenesis []. Growing evidence also indicates a close relationship between cardiovascular and neurological diseases. Cardiomyopathies are frequently observed in patients with neuromuscular disorders, including muscular dystrophies, congenital myopathies, myofibrillar myopathies, and metabolic myopathies [,,,,]. More recently, increasing attention has focused on the overlap between cardiovascular diseases and neurodegenerative disorders, which appear to share molecular pathways, biological mechanisms, and genetic risk factors [,]. A recent review by Cousineau and colleagues highlighted several biological links between cardiovascular diseases and neurodegenerative disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) []. These interactions involve common pathways related to mitochondrial dysfunction, neuroinflammation, autonomic regulation, vascular impairment, and cellular stress responses. In addition, several genes associated with cardiovascular diseases have also been implicated in neurological disorders, suggesting the existence of shared pathogenic mechanisms [].