Daily Cardiology Research Analysis
Analyzed 59 papers and selected 3 impactful papers.
Summary
Three impactful studies advance cardiovascular science and practice: a multicenter Fontan cohort integrating computational fluid dynamics (CFD) to guide conduit sizing, a large imaging cohort revealing non-linear and episodic growth dynamics of the ascending aorta, and an epigenome-wide analysis linking smoking-associated DNA methylation to mortality with mediation evidence. Together, they refine surgical planning, surveillance strategies in aortopathy, and mechanistic pathways of smoking-related cardiovascular risk.
Research Themes
- Computational physiology guiding congenital heart surgery
- Nonlinear and episodic aortic growth informing surveillance
- Epigenomic mechanisms linking smoking to cardiovascular mortality
Selected Articles
1. Outcomes of a physiology-driven extracardiac Fontan strategy incorporating computational fluid dynamics: a multicenter study.
In 788 extracardiac Fontan patients across 2009–2025, overall survival remained high with low early mortality. CFD-guided conduit sizing improved early postoperative hemodynamics in late-era patients but did not independently reduce mid-term clinical events after adjustment, supporting its role as decision support within individualized surgical planning.
Impact: This is a large, contemporary multicenter cohort demonstrating real-world outcomes and the pragmatic value of CFD in optimizing Fontan conduit geometry. It advances implementation of computational physiology in congenital heart surgery.
Clinical Implications: CFD-guided conduit sizing can be used as a decision-support tool to optimize early hemodynamics in extracardiac Fontan, while clinicians should not expect independent mid-term event reductions solely from sizing optimization. Selective fenestration and geometry-aware planning remain key for tailored care.
Key Findings
- Early mortality after extracardiac Fontan was 2.4% with 10-year survival of 92.5%.
- CFD-guided conduit sizing in Era II improved early postoperative hemodynamics.
- After adjustment, CFD-guided sizing did not independently reduce mid-term clinical events.
- Era II showed shorter pleural drainage and fewer prolonged effusions; fenestrated cases had higher event rates consistent with confounding by indication.
Methodological Strengths
- Multicenter cohort with large sample size and prespecified subgroup analyses
- Robust time-to-event methods including competing-risk analyses and multivariable adjustment
Limitations
- Retrospective design with potential residual confounding and selection bias (e.g., fenestration)
- CFD-guided sizing evaluated in a late-era subcohort; non-random allocation limits causal inference
Future Directions: Prospective studies or pragmatic trials integrating standardized CFD workflows could assess causal impact on clinical events and long-term Fontan physiology; model-informed strategies for antithrombotic management and conduit geometry warrant evaluation.
OBJECTIVES: To report early and mid-term outcomes after extracardiac total cavopulmonary connection (EC-TCPC) and to evaluate prespecified subgroup comparisons, including calendar-time era effects (Era I vs Era II), selective fenestration, conduit-size categories, and late-era computational fluid dynamics (CFD)-guided conduit sizing. METHODS: This multicentre retrospective cohort study included 788 patients who underwent EC-TCPC between 2009 and 2025. Patients were prespecified into Era I (2009-2016) and Era II (2017-2025) for calendar-time comparisons reflecting evolving pathway-based management; the CFD-guided subcohort was restricted to late-era patients. Survival and event-related outcomes were analyzed using Kaplan-Meier, competing-risk methods, and multivariable regression models. RESULTS: Early mortality was 2.4%. During a median follow-up of 8.2 years, overall survival was 97.2% at 1 year, 95.0% at 5 years, and 92.5% at 10 years. Freedom from major adverse events was 95.6%, 84.3%, and 75.3% at the same time points; the 10-year cumulative incidence of thromboembolism was 6.8% and of major adverse events was 23.6%. In the prespecified era comparison, Era II was associated with shorter pleural drainage duration and lower rates of prolonged pleural effusion. Fenestrated patients showed higher event rates, consistent with confounding by indication. In Era II, CFD-guided conduit sizing was associated with improved early postoperative haemodynamics but did not independently reduce mid-term clinical events after adjustment. CONCLUSIONS: A physiology-driven extracardiac Fontan strategy provides low early mortality and preserved mid-term survival. Selective fenestration and geometry-aware conduit sizing support individualized surgical planning, whereas CFD-guided optimization should be regarded as a decision-support tool rather than a causal determinant of outcome.
2. Changes of DNA methylation in smokers and ex-smokers referred for coronary angiography. Results from the LURIC study.
In an angiography cohort with discovery–replication EWAS, smoking was associated with 24,930 differentially methylated CpGs (11,907 novel), some persisting >10 years after cessation. A mortality-associated CpG score mediated the relationship between smoking and all-cause mortality, implicating epigenetic mechanisms in smoking-related cardiovascular risk.
Impact: This large EWAS with replication identifies thousands of novel smoking-associated methylation sites and provides mediation evidence linking epigenetic alterations to mortality. It advances mechanistic understanding and potential biomarker development for cardiovascular risk stratification.
Clinical Implications: DNA methylation signatures may refine residual cardiovascular risk assessment among smokers and ex-smokers beyond traditional factors, informing precision prevention strategies; persistence after cessation underscores the need for early intervention and monitoring.
Key Findings
- Meta-analysis identified 24,930 smoking-associated differentially methylated CpGs, including 11,907 not reported in prior large EWAS.
- A subset of methylation changes persisted more than 10 years after smoking cessation.
- A CpG score derived from mortality-associated DMPs strongly predicted all-cause mortality and mediated the smoking–mortality association.
Methodological Strengths
- Discovery–replication design with independent validation and meta-analysis
- Mediation analysis within a counterfactual framework linking epigenetic changes to outcomes
Limitations
- Observational design limits causal inference; residual confounding cannot be excluded
- Whole-blood methylation may not capture tissue-specific effects relevant to target organs
Future Directions: Prospective interventional studies assessing whether methylation-informed risk stratification or targeted prevention reduces events; exploration of tissue-specific methylation and integration with transcriptomic/causal inference methods (e.g., Mendelian randomization).
BACKGROUND: Tobacco smoking remains a major global health burden and is a leading risk factor for cardiovascular disease and cancer. Accumulating evidence suggests that tobacco smoke induces widespread alterations in DNA methylation, which may contribute to smoking-related morbidity and mortality. METHODS: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study is a monocentric prospective cohort including 3316 patients referred for coronary angiography. Genome-wide DNA methylation was assessed in 2423 participants using the Illumina HumanMethylationEPIC BeadChip. A discovery-replication design was applied (discovery n = 1262; replication n = 1161). Associations between smoking status (never/former vs. current) and CpG-specific methylation levels were evaluated using multivariable linear regression models. Cox proportional hazards models were used to assess associations with all-cause and cardiovascular mortality. Mediation was examined within a counterfactual framework using natural effect models. RESULTS: In the discovery sample, 14,403 CpG sites were significantly associated with smoking after false-discovery-rate correction (differentially methylated probes, DMPs). Of these, 3,000 were replicated in the independent sample at an FDR-adjusted p value < 0.05. In random-effect meta-analysis of both samples, 24,930 DMPs remained significant after multiple testing correction, of which 11,907 had not been reported in the largest published smoking EWAS to date. Among former smokers, a subset of DMPs remained differentially methylated more than 10 years after smoking cessation, indicating long-term persistence of smoking-associated epigenetic alterations. A CpG score constructed from mortality-associated DMPs was strongly associated with all-cause mortality. Inclusion of this score in Cox regression models attenuated the association between smoking status and mortality. Mediation analysis demonstrated a statistically significant natural indirect effect of smoking on all-cause mortality via the CpG score. CONCLUSIONS: Tobacco smoking is associated with widespread, exposure-dependent alterations in DNA methylation, many of which persist for years after cessation. These epigenetic changes are strongly linked to mortality risk and may represent an important biological pathway underlying the association between smoking and adverse health outcomes.
3. Nonlinear and Episodic Growth in the Natural History of Ascending Aortic Dilation.
In a 3,315-patient imaging cohort, baseline size (Z-score) showed a U-shaped, non-linear association with subsequent ascending aortic growth, and most enlarging aortas grew episodically rather than continuously. Age, sex, and blood pressure modified growth, challenging linear surveillance assumptions and threshold-based decision pathways.
Impact: This study reframes aortopathy progression as predominantly episodic with non-linear size–growth behavior, directly informing surveillance intervals and risk counseling. It challenges conventional linear growth models used in clinical decision-making.
Clinical Implications: Surveillance strategies for ascending aortic dilation should account for episodic growth and non-linear risk, potentially justifying dynamic imaging intervals and personalized thresholds that integrate modifiers like age, sex, and blood pressure.
Key Findings
- Baseline size (Z-score) had a U-shaped, non-linear association with subsequent growth (p<0.001).
- Among patients with total growth ≥2.0 mm, 81% exhibited episodic (discontinuous) growth patterns.
- Over half (58.3%) of enlargers started with non-dilated aortas (Z<2), and growth was modified by age, sex, and blood pressure.
Methodological Strengths
- Large imaging cohort with repeated CT/MR enabling trajectory phenotyping
- Use of generalized additive models and multivariable adjustment to capture non-linear effects
Limitations
- Single-center retrospective design may limit generalizability and introduce residual confounding
- Imaging intervals and modality heterogeneity could influence measured growth patterns
Future Directions: Prospective, multi-center validation of episodic growth phenotypes and testing adaptive surveillance algorithms; integration with biomechanical markers (e.g., wall stress) to refine individualized thresholds for intervention.
BACKGROUND: Predicting ascending aortic (AsAo) growth is challenging. Linear, continuous assumptions may oversimplify biology. We evaluated: (1) whether baseline body size-indexed diameter has a non-linear association with subsequent growth; and (2) whether patient-level trajectories are continuous or episodic. METHODS: Single-center, retrospective study (2012-2024). The Primary Cohort (n=3,315; ≥2 CT/MR scans) modeled the association between baseline indexed size (Z-score) and annualized growth using multivariable linear regression and generalized additive models (GAMs), adjusting for clinical covariates. A Sub-Cohort (n=1,055; ≥4 scans) was classified into longitudinal phenotypes: Stable (Total Growth <2.0 mm), Stable-with-Noise (Total Growth <2.0 mm with alternating small changes), Continuous Growth (Total Growth ≥2.0 mm without an episodic event), and Discontinuous/Episodic Growth (Total Growth ≥2.0 mm with ≥1 growth episode, defined as a diameter increase ≥2.0 mm within one interval or across two adjacent intervals). RESULTS: In the Primary Cohort, baseline Z-score showed a significant non-linear (U-shaped) association with subsequent growth in GAMs (p<0.001), with higher growth for small (Z<0) and severely dilated (Z>5) aortas. The size-growth relationship was significantly moderated by age, sex, blood pressure. In the Sub-Cohort, phenotype distribution was: Stable 50.4% (532/1,055), Stable-with-Noise 21.6% (228/1,055), Continuous 5.4% (57/1,055), and Discontinuous/Episodic 22.6% (238/1,055). Among patients with Total Growth ≥2.0 mm (n=295), 81% (238/295) were episodic and 58.3% (172/295) had a non-dilated baseline aorta (Z<2). CONCLUSION: The cohort-level size-growth relationship is non-linear, and episodic growth behavior dominates among those that enlarge. These findings support reassessing surveillance intervals, risk communication, and threshold-based decision pathways in thoracic aortic disease.