Weekly Cardiology Research Analysis
This week’s cardiology literature emphasized rapid translation across diagnostics, mechanism-driven targets, and population-level risk evidence. High‑quality randomized and registry studies supported AI-guided arrhythmia workflows and stage‑based device selection, while mechanistic and preclinical work nominated druggable targets (e.g., PRL2, TRPM7, PCSK9, CRYAB phosphorylation) for remodeling and ischemia–reperfusion injury. Large population cohorts and meta-analyses refined risk across real‑wo
Summary
This week’s cardiology literature emphasized rapid translation across diagnostics, mechanism-driven targets, and population-level risk evidence. High‑quality randomized and registry studies supported AI-guided arrhythmia workflows and stage‑based device selection, while mechanistic and preclinical work nominated druggable targets (e.g., PRL2, TRPM7, PCSK9, CRYAB phosphorylation) for remodeling and ischemia–reperfusion injury. Large population cohorts and meta-analyses refined risk across real‑world contexts (contraception arterial risk, AAS harms, anticoagulation in dialysis).
Selected Articles
1. Artificial intelligence for direct-to-physician reporting of ambulatory electrocardiography.
An ensemble AI (DeepRhythmAI) analyzed 14,606 ambulatory ECG recordings and, against cardiologist consensus, achieved markedly higher sensitivity for critical arrhythmias (98.6% vs 80.3% for technicians), reducing false negatives ~14-fold per patient. AI increased false positives modestly but demonstrated strong negative predictive value supporting direct-to-physician preliminary reporting to shorten delays and decrease missed events.
Impact: Demonstrates that an AI system can drastically reduce missed critical arrhythmias in large real-world ambulatory ECG datasets with cardiologist-adjudicated validation, enabling safer workflow redesign and faster clinician notification.
Clinical Implications: Health systems can pilot AI-first ambulatory ECG triage for prompt clinician alerts of high-risk events, with human review reserved for AI-flagged positives; implementation studies should address false-positive management and device/protocol generalizability.
Key Findings
- AI sensitivity for critical arrhythmias 98.6% vs technicians 80.3%.
- False negatives reduced from 44.3 to 3.2 per 1,000 patients by AI; false positives modestly higher (median 12 vs 5 per 1,000 patient-days).
2. Cardiomyocyte PRL2 Promotes Cardiac Hypertrophy via Directly Dephosphorylating AMPKα2.
This mechanistic study shows PRL2 is upregulated in hypertrophic myocardium (mouse and human) and functions as a phosphatase that directly dephosphorylates AMPKα2, suppressing AMPK signaling. Genetic PRL2 deficiency preserved AMPK activation and attenuated hypertrophy, fibrosis, and dysfunction in Ang II and TAC models, nominating PRL2 as a druggable nodal regulator of metabolic stress signaling.
Impact: Uncovers a direct enzyme–substrate interaction (PRL2→AMPKα2) that links metabolic stress control to remodeling, offering a concrete target (PRL2 inhibition/degradation) with potential to alter heart failure pathogenesis.
Clinical Implications: Translational work to develop selective PRL2 inhibitors or degraders is warranted; if safe and target‑engaging, PRL2 modulation could be tested to prevent or reverse pathological hypertrophy and HF progression.
Key Findings
- PRL2 upregulated in hypertrophic myocardium from mice and human HF tissue.
- PRL2 deficiency attenuated hypertrophy, fibrosis, and dysfunction in Ang II and TAC models.
- PRL2 directly interacts with and dephosphorylates AMPKα2, reducing AMPK signaling.
3. Stroke and myocardial infarction with contemporary hormonal contraception: real-world, nationwide, prospective cohort study.
In a Danish nationwide cohort of 2,025,691 women over >22 million person-years, combined oral contraceptives approximately doubled ischemic stroke and MI risk (adjusted IRR ≈2.0), progestin-only pills modestly increased risk, while levonorgestrel‑releasing intrauterine devices showed no increased arterial risk. Absolute event rates were low but clinically meaningful for counseling and contraceptive selection.
Impact: Provides one of the largest real‑world, method‑specific estimates of arterial thrombotic risk across contemporary contraceptives and identifies levonorgestrel IUD as a low‑arterial‑risk option, directly informing clinical counseling.
Clinical Implications: When arterial risk minimization is prioritized, levonorgestrel IUDs should be considered; discuss small but meaningful elevated arterial risks with combined or progestin-only systemic methods, especially in women with vascular risk factors.
Key Findings
- Combined oral contraception associated with ~2.0 adjusted rate ratio for ischemic stroke and MI vs non-use.
- Progestin-only pills had modestly increased arterial risk; levonorgestrel-releasing IUD showed no increased risk.
- Study covered 2,025,691 women with 22,209,697 person‑years and method-specific standardized rates.