Daily Cardiology Research Analysis
Analyzed 76 papers and selected 3 impactful papers.
Summary
Three standout cardiology papers span clinical AI, ablation technology, and mechanistic cardio-oncology. A randomized trial in Nature Medicine shows that a large language model can enhance complex cardiology decision-making with fewer clinically significant errors. Long-term randomized data support durable effectiveness of pulsed field ablation versus thermal ablation, while a mechanistic study unveils a PGAM1–VDAC1–cGAS-STING–ferroptosis axis driving doxorubicin cardiotoxicity.
Research Themes
- AI decision support in complex cardiology
- Long-term outcomes of pulsed field ablation
- Mechanisms of doxorubicin cardiotoxicity
Selected Articles
1. A large language model for complex cardiology care.
In a randomized evaluation of complex cardiology cases, AMIE (a large language model) improved assessment quality: subspecialists preferred AMIE-assisted plans more often, with fewer clinically significant errors and less missing content. Participating cardiologists reported perceived benefit and time savings with AMIE assistance.
Impact: This is among the first randomized trials showing practical, measurable benefits of an LLM in subspecialty cardiology decision-making. It establishes a quality signal beyond diagnostic accuracy metrics, focusing on clinically significant errors and completeness.
Clinical Implications: LLM-assisted reviews could augment general cardiologists managing complex genetic cardiomyopathy cases, reducing harmful errors and omissions. Integration should be staged, with human oversight, audit trails, and local validation before broader deployment.
Key Findings
- Subspecialists preferred AMIE-assisted assessments 46.7% vs 32.7% for unaided cardiologists (P=0.02).
- Clinically significant errors were lower with AMIE assistance: 13.1% vs 24.3% (P=0.033).
- Missing content decreased with AMIE: 17.8% vs 37.4% (P=0.0021).
- Cardiologists reported AMIE helped in 57.0% and saved time in 50.5% of cases.
Methodological Strengths
- Randomized controlled design with blinded subspecialist adjudication across ten domains
- Access to raw multimodal diagnostic data (ECG, echo, CMR, CPET) for realistic case management
Limitations
- Retrospective patient data and no direct patient outcomes or safety endpoints
- Single experimental LLM and limited number of participating clinicians may limit generalizability
Future Directions: Prospective trials linking AI-assisted decisions to patient outcomes, cost-effectiveness analyses, and benchmarking across multiple LLMs and health systems with robust safety governance.
The scarcity of subspecialist medical expertise poses a considerable challenge for healthcare delivery. This issue is particularly acute in cardiology, where timely, accurate management determines outcomes. We explored the potential of Articulate Medical Intelligence Explorer (AMIE), a large language model-based experimental medical artificial intelligence system, to augment clinical decision-making in this challenging context. We conducted a randomized controlled trial comparing large language model-assisted care with the usual care of complex patients suspected of having a genetic cardiomyopathy, and we curated a real-world dataset of complex cases from a subspecialist cardiology practice. Nine participating general cardiologists were provided with access to both clinical text reports and raw diagnostic data-including electrocardiograms, echocardiograms, cardiac magnetic resonance imaging scans and cardiopulmonary exercise testing-and were randomized to manage these cases, either with or without assistance from AMIE. We developed a ten-domain evaluation rubric used by three blinded subspecialists to evaluate the quality of triage, diagnosis and management. In our randomized controlled trial with retrospective patient data, subspecialists favored large language model-assisted responses overall, and for the management plan and diagnostic testing domains, with the remaining domains considered a tie. Overall, subspecialists preferred AMIE-assisted cardiology assessments 46.7% of the time, compared with 32.7% for cardiologists alone (P = 0.02), with 20.6% rated as a tie. Subspecialists also quantified errors, extra and missing content, reasoning and potential bias. Cardiologists alone had more clinically significant errors (24.3% versus 13.1%, P = 0.033) and more missing content (37.4% versus 17.8%, P = 0.0021) than cardiologists assisted by AMIE. Lastly, cardiologists who used AMIE reported that AMIE helped their assessment more than half the time (57.0%) and saved time in 50.5% of cases.
2. Pulsed Field versus Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation: 4-Year Outcomes in the ADVENT-LTO Study.
Four-year follow-up of the randomized ADVENT trial shows maintained effectiveness of pulsed field ablation versus thermal ablation for paroxysmal AF, with fewer repeat ablations and a trend toward fewer hospital-based arrhythmia interventions. These durable data reinforce PFA’s role given its established safety advantages.
Impact: First robust long-term (≈4-year) randomized follow-up comparing PFA and thermal ablation demonstrates durable performance and procedural efficiency advantages, informing technology adoption and lifetime management strategies in AF.
Clinical Implications: For paroxysmal AF, PFA can be considered a first-line ablation modality given durable outcomes and fewer repeat procedures, especially when balanced with its favorable safety profile (e.g., reduced collateral thermal injury).
Key Findings
- Four-year treatment success: 72.8% (PFA) vs 64.1% (thermal), P=0.12.
- Freedom from hospital-based arrhythmia intervention favored PFA (HR 0.64, 95% CI 0.38–1.05).
- Repeat ablations were fewer with PFA: 10.4% vs 17.7% (P=0.04).
- Trend toward reduced progression to persistent AF with PFA (HR 0.55, 95% CI 0.16–1.88).
Methodological Strengths
- Randomized comparator with extended follow-up (~4 years) in a sizable cohort (n=364)
- Pre-specified outcomes including repeat ablation and arrhythmia-related interventions
Limitations
- Primary endpoint difference was not statistically significant at 4 years
- Extension study may be underpowered for some secondary endpoints; post-trial therapy effects possible
Future Directions: Head-to-head randomized trials powered for long-term clinical endpoints (e.g., hospitalization, stroke) and health-economic analyses comparing PFA with thermal modalities across AF subtypes.
Pulsed field ablation (PFA) has proven to be a safe and effective non-thermal ablation modality for the treatment of atrial fibrillation (AF), but little outcome data beyond 1 year has been reported. Here, we present results from the ADVENT-LTO study, which provides extended follow-up of the ADVENT trial, the first randomized trial comparing PFA with conventional thermal ablation. In ADVENT-LTO, 364 paroxysmal AF patients (183 PFA, 181 thermal; 237 men, 127 women) participated, and were followed for 1,332±147 days. For the primary endpoint of four-year treatment success, PFA demonstrated preserved effectiveness compared to thermal ablation (72.8% PFA, 64.1% thermal; P=0.12). Moreover, there was a trend favoring PFA as compared to thermal ablation for the pre-specified outcome of freedom from hospital-based arrhythmia intervention (85.6% PFA, 78.6% thermal; HR 0.64, 95%CI 0.38, 1.05), including fewer repeat ablations (10.4% PFA, 17.7% thermal; P=0.04), as well as a trend favoring PFA as compared to thermal ablation for the pre-specified outcome of progression to persistent AF (2.6% PFA, 4.6% thermal; HR 0.55, 95%CI 0.16, 1.88). Taken together, these data demonstrate that the favorable outcomes of PFA are maintained over the course of four years. Coupled with the safety advantages of PFA over thermal ablation, these long-term data support widespread adoption of PFA for the treatment of AF. Clinical Trial Registration: NCT06526546.
3. PGAM1-dependent VDAC1 oligomerization disrupts mitochondrial quality control to drive doxorubicin cardiotoxicity via the cGAS-STING-ferroptosis axis.
This mechanistic study identifies a PGAM1-driven VDAC1 oligomerization pathway that collapses mitochondrial quality control, triggers ER stress and mtDNA leakage, activates cGAS-STING, and culminates in ferroptosis during doxorubicin cardiotoxicity. Genetic ablation of PGAM1 protected mice, and pharmacologic perturbations validated pathway causality.
Impact: Revealing a coherent PGAM1–VDAC1–cGAS-STING–ferroptosis axis connects metabolic enzymes, mitochondrial membrane dynamics, innate immunity, and regulated cell death in cardiotoxicity, opening multiple druggable nodes for cardio-oncology.
Clinical Implications: Targeting PGAM1/VDAC1 interactions or downstream STING activation may mitigate anthracycline cardiotoxicity; the pathway also suggests potential biomarkers (e.g., mtDNA, ferroptosis markers) for risk stratification and monitoring.
Key Findings
- Doxorubicin upregulated PGAM1 in cardiomyocytes; PGAM1-cKO mice were protected from dysfunction, fibrosis, and inflammation.
- PGAM1 promoted pathological VDAC1 oligomerization, collapsing mitochondrial quality control and inducing ER stress with cytosolic mtDNA leakage.
- Cytosolic mtDNA activated cGAS-STING, a critical upstream driver of cardiomyocyte ferroptosis; pharmacologic manipulation confirmed pathway causality.
Methodological Strengths
- In vivo genetic model (cardiomyocyte-specific PGAM1 knockout) with functional and histologic readouts
- Multimodal mechanistic validation (biochemistry, imaging, co-IP, pharmacologic perturbation) across in vivo and in vitro systems
Limitations
- Preclinical models; translational relevance to human patients and dosing regimens requires validation
- Potential off-target effects of pharmacologic tools and context-specificity of ferroptosis in human myocardium
Future Directions: Test PGAM1 or STING inhibitors as cardioprotective co-therapies in anthracycline regimens; develop and validate circulating biomarkers (e.g., mtDNA, lipid peroxidation indices) to guide precision cardio-oncology.
OBJECTIVES: Doxorubicin (Dox) is a potent chemotherapeutic agent whose clinical use is limited by severe cardiotoxicity. The underlying molecular mechanisms remain incompletely understood. This study aimed to investigate the role of the phosphoglycerate mutase 1 (PGAM1)/voltage-dependent anion channel 1 (VDAC1) axis in early-stage Dox-induced cardiotoxicity, focusing on its impact on mitochondrial quality control (MQC), endoplasmic reticulum (ER) stress, and the subsequent activation of innate immune signaling. METHODS: We established a short-term cumulative Dox-induced cardiomyopathy model using wild-type and cardiomyocyte-specific PGAM1 knockout (PGAM1-CKO) mice. Cardiac function was assessed by echocardiography. In vitro experiments were performed on neonatal mouse cardiomyocytes (NMCMs) and HL-1 cells. Molecular techniques including Western blotting, immunofluorescence, co-immunoprecipitation, and quantitative PCR were used to dissect the signaling pathway. Key pathway components were validated using specific pharmacological inhibitors and activators. RESULTS: Dox treatment significantly upregulated PGAM1 expression in cardiomyocytes. PGAM1-CKO mice were protected from Dox-induced cardiac dysfunction, fibrosis, and inflammation. Mechanistically, Dox-induced PGAM1 promoted the pathological oligomerization of VDAC1. This PGAM1-VDAC1 interaction triggered the collapse of MQC and induced ER stress, leading to the leakage of mitochondrial DNA (mtDNA) into the cytosol. The released cytosolic mtDNA subsequently activated the cGAS-STING innate immune pathway, which we identified as a critical upstream driver of cardiomyocyte ferroptosis. Pharmacological induction of VDAC1 oligomerization or STING activation abolished the cardioprotective effects observed in PGAM1-CKO mice. CONCLUSION: Our findings reveal a novel PGAM1/VDAC1 signaling axis that triggers early Dox-induced cardiotoxicity. This axis disrupts mitochondrial homeostasis, leading to mtDNA release, which activates the cGAS-STING pathway and ultimately culminates in cardiomyocyte ferroptosis. Targeting the PGAM1/VDAC1 interaction presents a promising therapeutic strategy to mitigate Dox-induced cardiac injury.