Congenital Heart Disease (CHD) encompasses a range of structural abnormalities of the heart and great vessels present at birth and is associated with significant lifelong morbidity, including heart failure and arrhythmias. Early diagnosis is critical for optimizing perinatal management and improving outcomes. This review focuses on early fetal echocardiography, a specialized ultrasound technique that enables detection of cardiac abnormalities in utero, as early as 11-14 weeks of gestation, compared to traditional imaging performed at approximately 20 weeks. Advancements in early imaging have improved the identification of high-risk fetuses, particularly those with genetic predispositions or family history of CHD, allowing for earlier clinical decision-making and intervention planning. In select cases, prenatal detection facilitates in utero management of conditions such as aortic stenosis and hypoplastic left heart syndrome. Additionally, emerging applications of artificial intelligence (AI) have enhanced image analysis and diagnostic accuracy, supporting clinicians in the early recognition of CHD. Despite these advances, challenges remain, including variability in diagnostic accuracy in early gestation, risk of false positives, and limited access to specialized imaging technologies. Continued integration of AI-driven tools and the development of standardized screening protocols hold promise for improving diagnostic consistency and long-term outcomes in patients with CHD.
Background:Mulibrey nanism is a rare autosomal recessive genetic disorder caused by homozygous or compound heterozygous mutations in the tripartite motif protein 37 (TRIM37 gene), which codes for a RING finger E3 ubiquitin ligase. Affected individuals present with prenatal-onset growth failure, abnormalities in multiple organs, and heart disorders, including constrictive pericarditis and restrictive cardiomyopathy. Methods and Results:We performed phenotypic-genotypic analyses in a 32-week gestation preterm infant presenting with a complex congenital heart disease, including interrupted aortic arch type B, persistent left-sided superior vena cava (SVC), septal defects, and valvular disease, in addition to other congenital malformations. Initial genetic screenings, including whole genome chromosomal microarray, were negative. Whole exome sequencing (WES) of DNA samples from the proband/mother duo revealed two novel heterozygous missense variants [c.199C>T (p.Arg67Cys)] and [c.2041C>G (p.Gln681Glu)] in the TRIM37 gene, which has been associated with Mulibrey nanism. The c.199C>T variant was inherited from the mother; however, the mode of inheritance of the c.2041C>G could not be ascertained. Whether the two variants are present on the same allele could not be determined either, due to the unavailability of the father or any family member for additional genetic analysis. However, in silico analysis predicted that both variants are damaging, and both amino acid positions are fairly well conserved. Conclusion:These findings highlight the critical role of the TRIM37 genetic variants in complex congenital heart defect phenotypes associated with Mulibrey nanism and emphasize the importance of comprehensive triobased WES for antenatal care and early diagnosis.
Background:Heart failure (HF), atrial fibrillation (AF)/atrial flutter (AFL) and sepsis commonly co-occur in hospitalized patients. This study determines temporal mortality trends associated with concurrent HF, AF/AFL, and sepsis among adults across demographic and geographic groups in the United States. Methods:The CDC Wonder database was utilized to extract age-adjusted mortality rates (AAMR) per 100,000 for deaths listing HF, AF/AFL, and sepsis. Trends were analyzed by age, race/ethnicity, region, and sex. Joinpoint regression calculated the annual percent change (APC) and average annual percent change (AAPC) for AAMR with 95% CI. Results:From 1999 to 2023, there were 1,749,565 deaths involving HF, AF/AFL, and sepsis. AAMR doubled (1999: 11.79 vs 2020: 23.87 per 100,000), with a critical 2012 inflection point accelerating mortality from 1.29% to 6.42% annually. White individuals had steepest post-2012 acceleration (6.67%), surpassing Black individuals by 2020 (24.88 vs 20.80 per 100,000). Males had higher AAMRs than females (28.69 vs 20.19 per 100,000 in 2020). Middle-aged adults (45-64 years) showed highest acceleration (9.98-10.30%), nearly double those aged ≥85 years (5.82%). The Midwest and South had steepest increases (7.07% and 7.11%). During 2018-2023, mortality continued increasing at 6.11% annually without stabilization. Conclusions:Mortality involving HF, AF/AFL and sepsis doubled from 1999-2023 with sustained acceleration and no post-pandemic stabilization. Targeted interventions should focus on males, middle-aged adults, and high-risk regions with enhanced post-discharge care.
