Daily Cardiology Research Analysis
Three impactful cardiology papers stood out today: a network meta-analysis links psoriasis biologics to differential cardiovascular risk; deep learning echocardiography markedly improves detection of transthyretin cardiac amyloidosis with low bias; and phosphoproteomics implicates DYRK1A as a kinase driver of incomplete reverse remodelling after aortic valve replacement, suggesting a new therapeutic target.
Summary
Three impactful cardiology papers stood out today: a network meta-analysis links psoriasis biologics to differential cardiovascular risk; deep learning echocardiography markedly improves detection of transthyretin cardiac amyloidosis with low bias; and phosphoproteomics implicates DYRK1A as a kinase driver of incomplete reverse remodelling after aortic valve replacement, suggesting a new therapeutic target.
Research Themes
- AI-enabled echocardiographic diagnosis and fairness auditing
- Cardiovascular safety of systemic immunomodulators in psoriasis
- Phosphoproteomics and kinase targets in cardiac reverse remodelling
Selected Articles
1. Cardiovascular and Kidney Outcomes After Systemic Treatment for Plaque Psoriasis: A Systematic Review and Network Meta-analysis.
In 68 RCTs (n=34,414), bimekizumab ranked highest for PASI75 and reduced total cardiovascular events versus placebo, whereas ixekizumab increased MACE despite strong PASI90 efficacy. Renal outcomes were similar across treatments. Findings suggest cardiovascular safety differences among psoriasis biologics.
Impact: This NMA integrates a large RCT evidence base to quantify treatment efficacy alongside cardiovascular safety signals, directly informing therapeutic choices in patients at elevated cardiovascular risk.
Clinical Implications: For psoriasis patients with high cardiovascular risk, bimekizumab may be preferred; ixekizumab should be used cautiously with cardiovascular risk assessment and monitoring. Multidisciplinary cardio-dermatology collaboration and postmarketing surveillance are warranted.
Key Findings
- Across 68 RCTs (n=34,414), bimekizumab improved PASI75 and reduced total cardiovascular events versus placebo (OR 0.06, 95% CI 0–0.80).
- Ixekizumab achieved superior PASI90 but increased MACE versus placebo (OR 3.26, 95% CI 1.26–9.31) and versus bimekizumab.
- Renal outcomes did not differ meaningfully among systemic agents; evidence certainty was high for efficacy and moderate for cardiovascular outcomes.
Methodological Strengths
- Prospective protocol registration (PROSPERO) with duplicate study selection and data extraction
- Network meta-analysis enabling indirect comparisons across 68 RCTs with SUCRA-based ranking and certainty grading
Limitations
- Heterogeneity across trials and low event rates for cardiovascular outcomes
- Most included RCTs were not primarily designed or powered for cardiovascular or renal endpoints; need for real-world data
Future Directions: Leverage real-world registries and postmarketing data to validate cardiovascular safety signals and consider head-to-head trials in high-risk populations; mechanistic studies to elucidate differential CV effects.
2. Evaluating the Performance and Potential Bias of Predictive Models for Detection of Transthyretin Cardiac Amyloidosis.
In a matched heart failure cohort (176 ATTR-CM cases; 3,192 controls), two deep learning echocardiography models (AUC 0.88 and 0.92) outperformed a regression score and a claims-based model and met fairness criteria for equal opportunity in Black patients. Claims-based random forest detection performed poorly (AUC 0.49).
Impact: Demonstrates superior diagnostic performance and fairness of deep learning echo models for ATTR-CM, which could reduce diagnostic delays and improve access to disease-modifying therapy.
Clinical Implications: Integrating validated deep learning echo models into heart failure workflows could flag suspected ATTR-CM for confirmatory scintigraphy/MRI and TTR testing, expediting treatment decisions while maintaining equity.
Key Findings
- Echo-based deep learning models achieved AUC 0.88 (EchoNet-LVH) and 0.92 (EchoGo Amyloidosis), surpassing the Mayo ATTR-CM score (AUC 0.79) and a claims-based random forest model (AUC 0.49).
- Fairness auditing met equal opportunity criteria among patients who identified as Black.
- External validation used a matched heart failure cohort with an enriched 5% prevalence (176 cases; 3,192 controls).
Methodological Strengths
- Head-to-head comparison of four distinct algorithms with external validation and DeLong testing
- Formal fairness auditing using standard metrics to assess potential harms due to model bias
Limitations
- Single integrated health system and enriched case prevalence may limit generalizability and introduce spectrum bias
- Retrospective design; prospective impact on diagnostic timelines and outcomes not assessed
Future Directions: Prospective implementation studies assessing diagnostic yield, time-to-diagnosis, cost-effectiveness, and equity across diverse systems; continuous learning and multi-center validation.
3. Myocardial phosphoproteomics unveils a key role of DYRK1A in aortic valve replacement-induced reverse remodelling.
Proteomic and phosphoproteomic profiling of AVR patients revealed inflammatory/complement activation and reduced ATP production in incomplete reverse remodelling, whereas complete remodelling associated with better mitochondrial function. Kinase inference highlighted DYRK1A, whose activity inversely correlated with LV mass regression, nominating a potential therapeutic target.
Impact: Combining myocardial phosphoproteomics with metabolic modelling identifies DYRK1A as a mechanistic driver of incomplete reverse remodelling after AVR, advancing target discovery for post-AVR heart failure risk.
Clinical Implications: While preliminary, DYRK1A inhibition may represent a strategy to augment reverse remodelling after AVR; profiling could stratify patients at risk for incomplete remodelling and guide adjunctive therapies.
Key Findings
- LC-MS/MS identified 83 dysregulated myocardial proteins distinguishing complete (≥15% LV mass regression) vs incomplete (≤5%) reverse remodelling groups.
- Gene ontology and kinetic metabolic modelling pointed to inflammation/complement activation and lower ATP production capacity in incomplete remodelling; complete remodelling showed better mitochondrial function.
- Phosphoproteomic kinase inference implicated DYRK1A; its activity inversely correlated with LV mass regression (r = −0.62), suggesting a therapeutic target.
Methodological Strengths
- Integrated myocardial proteomics/phosphoproteomics with gene ontology and kinase inference
- Kinetic metabolic modelling corroborated bioenergetic deficits in incomplete reverse remodelling
Limitations
- Sample size and exact cohort numbers not specified in the abstract; likely limited clinical generalizability
- Associational findings without interventional validation of DYRK1A modulation; abstract truncated
Future Directions: Validate DYRK1A as a modifiable target in larger human cohorts and preclinical models; test kinase inhibitors to enhance reverse remodelling; integrate multi-omics to refine patient stratification post-AVR.