Background: In the 1990s, there were few multicenter research collaborations and pediatric cardiovascular clinical trials. The National Heart, Lung, and Blood Institute at the National Institutes of Health established the Pediatric Heart Network (PHN) in 2001 to stimulate multi-center collaboration and clinical studies in children and adults with congenital heart disease (CHD) and pediatric acquired heart disease. Methods: The PHN developed a flexible infrastructure for multi-center collaborative clinical research in children and adults with CHD and pediatric acquired heart disease. The objectives of the PHN are to improve health outcomes in individuals of all ages with CHD and pediatric acquired heart disease, to disseminate findings to improve treatment options and standards of care, to train and educate new investigators, and to support families during the conduct of clinical research. Results: To date, the PHN has conducted 30 studies, including 13 clinical trials, across over 60 sites and has enrolled over 10,000 participants. PHN studies have impacted clinical practice and guidelines in CHD and have supported the career development of young investigators, research nurses, and study coordinators. None of this would have been possible without the many partnerships with patient advocacy organizations, the U.S. Food and Drug Administration, a variety of industry collaborators and clinical registries. PHN studies have leveraged registry data to improve efficiency, minimize burden and reduce errors in data collection. Conclusion: The PHN’s success is due to fostering collaboration across pediatric cardiology centers, creating a clinical research infrastructure that can adapt to different types of studies, and emphasizing career development of young investigators and research coordinators. This paper will summarize the PHN’s history, partnerships, use of clinical registries, future directions, and ways to get involved.
Atherosclerotic cardiovascular disease remains the leading cause of global mortality, with low-density lipoprotein cholesterol established as a primary causal risk factor. Despite widespread implementation of statin therapy, substantial interindividual variability in treatment response persists, necessitating precision medicine approaches to optimize therapeutic outcomes. This comprehensive narrative review synthesizes current understanding of pharmacogenomic determinants influencing lipid-lowering therapy efficacy, examines mechanisms underlying residual cardiovascular risk, and evaluates emerging therapeutic modalities targeting previously unexploited pathways in lipid metabolism. Genetic variants in key genes including 3-hydroxy-3-methylglutaryl-CoA reductase, apolipoprotein E, low-density lipoprotein receptor, and proprotein convertase subtilisin/kexin type 9 demonstrate significant associations with differential treatment responses, with specific polymorphisms conferring enhanced efficacy or increased intolerance risk. Beyond traditional statin therapy, novel therapeutic approaches targeting proprotein convertase subtilisin/kexin type 9, angiopoietin-like protein 3, apolipoprotein C-III, and ATP citrate lyase offer substantial low-density lipoprotein cholesterol reductions of 50–80%, while RNA-based therapies including antisense oligonucleotides and small interfering RNA provide precise molecular targeting capabilities. Despite intensive lipid-lowering interventions, residual cardiovascular risk persists through four principal mechanisms: triglyceride-rich lipoproteins, lipoprotein(a), inflammatory processes, and suboptimal treatment adherence. Integration of pharmacogenomic insights with emerging therapeutic modalities enables personalized risk stratification and treatment selection, representing a paradigm shift toward precision medicine in cardiovascular disease prevention and management.
Background: Four-dimensional (4D) ultrasound is increasingly being used for prenatal diagnosis of congenital heart disease (CHD). We aimed to perform a systematic review and meta-analysis to evaluate its diagnostic accuracy for fetal CHD. Methods: This systematic review was conducted in accordance with the PRISMA-DTA guidelines. We systematically searched eight databases for studies published up to July 22, 2025. Data were extracted to calculate diagnostic accuracy metrics, study quality was assessed using QUADAS-2, and a bivariate random-effects model was used for the meta-analysis. Results: A total of 49 studies were included, comprising 45 retrospective and 4 prospective studies, which were mainly (91.8%) conducted in China. These studies involved 23,397 fetuses, among which 2115 were diagnosed with congenital heart disease. The pooled sensitivity of 4D ultrasound for diagnosing fetal congenital heart disease was 0.91 (95% CI: 0.89–0.93), the pooled specificity was 0.98 (95% CI: 0.97–0.99), and the area under the summary receiver operating characteristic (SROC) curve (AUC) was 0.98 (95% CI: 0.96–0.99). Although 4D ultrasound technology can be implemented as early as 11 weeks of gestation, its diagnostic sensitivity and specificity reached a superior level and stabilized at an average of 20 weeks of gestation (range 14–28 weeks). Meta-regression indicated that sample size and prior suspicion of fetal CHD were significant contributors to heterogeneity (p < 0.05). Conclusion: Four-dimensional ultrasound has high diagnostic efficacy for fetal CHD and is suitable for prenatal screening of fetal CHD, and the diagnostic effect is optimal and stable at an average gestational age of 20 weeks (range 14–28 weeks).
