Daily Cardiology Research Analysis
Analyzed 150 papers and selected 3 impactful papers.
Summary
Three impactful cardiology studies span mechanistic, epidemiologic, and clinical trial domains: a Cell Metabolism study identifies a gut microbe–derived metabolite (isovaleric acid) that protects against atrial fibrillation via GPR109A/STAT3–GSDME pathways; the PORTHOS population study in European Heart Journal reveals very high heart failure prevalence with >90% HFpEF and underdiagnosis in adults ≥50; and a prespecified FINEARTS-HF analysis supports eGFR-based finerenone dosing down to eGFR 25 mL/min/1.73 m² in HFmrEF/HFpEF.
Research Themes
- Microbiome–cardiac electrophysiology axis and arrhythmia mechanisms
- Population burden and detection of HFpEF in aging societies
- Kidney function–based dosing strategies for cardio-renal therapeutics
Selected Articles
1. Gut microbiota-derived isovaleric acid alleviates atrial fibrillation by suppressing GSDME-dependent pyroptosis.
Across clinical cohorts and animal models, Ruminococcus gnavus–derived isovaleric acid reduced atrial fibrillation susceptibility and atrial fibrosis. IVA activates GPR109A on atrial cardiomyocytes, dampening IL-6/STAT3 signaling and blocking GSDME-dependent pyroptosis, thereby interrupting a STAT3–GSDME feedforward loop.
Impact: This study uncovers a microbiome–metabolite–host signaling axis that mechanistically links dietary amino acid metabolism to arrhythmia suppression, revealing GPR109A/STAT3–GSDME as actionable nodes.
Clinical Implications: While not practice-changing yet, the data support clinical exploration of IVA supplementation, targeted probiotics (e.g., R. gnavus), or GPR109A agonism as novel anti-arrhythmic strategies and biomarkers linking diet–microbiome–AF risk.
Key Findings
- R. gnavus colonization or exogenous isovaleric acid reduced AF susceptibility and atrial fibrosis in vivo.
- R. gnavus converts dietary leucine to isovaleric acid via the enzyme vorC (2-oxoisovalerate ferredoxin reductase γ-subunit).
- Isovaleric acid activates GPR109A on atrial cardiomyocytes, suppresses IL-6/STAT3 signaling, and blocks GSDME-dependent pyroptosis.
Methodological Strengths
- Integrated multi-system approach spanning clinical cohorts, multiple animal models, and cellular mechanistic validation.
- Precise metabolite–receptor–pathway mapping (IVA–GPR109A–STAT3/GSDME) with functional readouts.
Limitations
- Lack of interventional human trials; translational efficacy and safety of IVA or probiotics remain unproven.
- Dose–response, long-term effects, and generalizability across diverse AF phenotypes are not established.
Future Directions: Conduct early-phase trials of IVA supplementation or targeted probiotics; evaluate selective GPR109A agonists; longitudinally link dietary leucine–IVA axis to AF outcomes and patient subphenotypes.
Atrial fibrillation (AF), a common and clinically significant cardiac rhythm disturbance, is associated with gut microbial dysbiosis. However, the precise role of the microbiota and associated metabolism in this condition remain unclear. Through integrated analysis of clinical cohorts and multiple animal models, we identified an intestinal symbiont, Ruminococcus gnavus (R. gnavus), which suppresses the occurrence of AF and atrial fibrosis by producing the leucine-derived branched-chain fatty acid isovaleric acid (IVA). R. gnavus colonization or exogenous IVA supplementation reduced AF susceptibility and improved fibrosis-driven atrial remodeling. Mechanistically, R. gnavus metabolizes dietary leucine into IVA through its unique enzyme 2-oxoisovalerate ferredoxin reductase γ-subunit (vorC). Microbiome-derived IVA activates G protein-coupled receptor 109A (GPR109A) on atrial cardiomyocytes, inhibiting interleukin (IL)-6/signal transducer and activator of transcription 3 (STAT3) signaling activation and blocking gasdermin E (GSDME)-mediated pyroptosis through a STAT3-GSDME feedforward circuit. These results reveal that the microbial metabolism of dietary leucine and the production of IVA play pivotal roles in preventing AF onset and progression.
2. Efficacy and Safety of the Kidney Function-Based Finerenone Dosing Strategy Used in FINEARTS-HF.
In a prespecified analysis of 5,986 HFmrEF/HFpEF patients, eGFR-guided finerenone dosing achieved consistent reductions in the primary outcome across high- and low-eGFR strata, with safety profiles that were similar between strata. The odds reduction for hypokalemia was greater in the higher eGFR/high-dose stratum.
Impact: Provides practical dosing guidance for finerenone in HFmrEF/HFpEF patients with impaired renal function, supporting use down to eGFR 25 mL/min/1.73 m².
Clinical Implications: Clinicians can implement eGFR-based finerenone dosing for HFmrEF/HFpEF with monitoring, enabling broader use in patients with CKD while maintaining safety, including potassium management.
Key Findings
- Across 5,986 patients, finerenone reduced the primary outcome consistently in both dosing strata (rate ratio 0.77 vs 0.87; interaction P=0.34).
- Safety was comparable between strata; reduction in hypokalemia odds with finerenone vs placebo was greater in the higher eGFR/high-dose stratum (P-interaction <0.01).
- Effective and safe use was observed down to baseline eGFR 25 mL/min/1.73 m².
Methodological Strengths
- Prespecified analysis within a large randomized trial with clear dosing strata by renal function.
- Consistent effects across strata on primary and secondary outcomes with robust statistical assessment (interaction testing).
Limitations
- As a stratified prespecified analysis, it was not powered for definitive interaction effects.
- Follow-up duration and applicability beyond the studied eGFR range (<25 mL/min/1.73 m²) remain untested.
Future Directions: Implementation studies for eGFR-based dosing in routine care; evaluate potassium-monitoring protocols; explore efficacy in eGFR <25 and across diverse HF phenotypes.
BACKGROUND: Given that mineralocorticoid receptor antagonists have the potential to impair renal function and induce hyperkalemia, close monitoring of estimated glomerular filtration rate (eGFR) and serum potassium levels is essential to ensure the safe administration of this therapy. OBJECTIVES: In this prespecified analysis, the authors evaluated the efficacy and safety of the kidney function-based finerenone dosing strategy used in the FINEARTS-HF trial. METHODS: In FINEARTS-HF, patients with an eGFR of 25 to 60 mL/min/1.73 m RESULTS: Among 5,986 (99.8%) analyzable patients, 3,159 were assigned to the higher eGFR/high-dose stratum and 2,827 to the lower eGFR/low-dose stratum group. The mean ± SD achieved dose was 32.3 ± 9.1 mg (finerenone) and 34.4 ± 7.8 mg (placebo) in the higher eGFR/high-dose stratum, and 15.6 ± 4.3 mg (finerenone) and 16.7 ± 4.0 mg (placebo) in the lower eGFR/low-dose stratum. The effect of finerenone on the primary outcome was consistent across the 2 dosing strata (higher eGFR/high-dose stratum: rate ratio: 0.77 [95% CI: 0.63-0.94] vs lower eGFR/low-dose stratum: rate ratio: 0.87 [95% CI: 0.74-1.03]; P for interaction = 0.34). Consistent benefits were observed for the components of the primary outcome and all-cause death. Safety was also consistent between dosing strata, except for hypokalemia, where the reduction in the odds of hypokalemia with finerenone compared to placebo was greater in the higher eGFR/high-dose stratum (P-interaction < 0.01). CONCLUSIONS: In FINEARTS-HF, an eGFR-based dosing strategy allowed effective and safe use of finerenone in patients with heart failure with mildly reduced ejection fraction/ heart failure with preserved ejection fraction with a baseline eGFR as low as 25 mL/min/1.73 m
3. Heart failure in the Portuguese population aged ≥50 years: prevalence and phenotypes in the PORTHOS study.
In a population-based two-stage screening of 6,189 adults ≥50, heart failure prevalence was 16.54% with sharp age and sex gradients; 93.4% were HFpEF and 90% were previously undiagnosed. Findings endorse NT-proBNP screening plus echocardiography to detect HF, particularly HFpEF, in aging populations.
Impact: Defines contemporary, high HFpEF burden and underdiagnosis in community-dwelling older adults using standardized ESC/HFA-PEFF criteria, informing screening and health policy.
Clinical Implications: Supports targeted NT-proBNP-based screening and echocardiographic confirmation to identify undiagnosed HFpEF, emphasizing strategies for older adults and women.
Key Findings
- Estimated HF prevalence was 16.54% among adults ≥50, rising steeply with age and higher in females (21.00%) than males (10.47%).
- HFpEF accounted for 93.4% of HF cases; approximately 90% of HF cases were previously undiagnosed.
- HFpEF was independently associated with older age, female sex, type 2 diabetes, atrial fibrillation, and dyslipidemia.
Methodological Strengths
- Population-based, two-stage design integrating NT-proBNP screening with echocardiographic confirmation.
- Use of up-to-date ESC 2021 and HFA-PEFF diagnostic frameworks for standardized phenotyping.
Limitations
- Cross-sectional design limits causal inference and temporal trends.
- Single-country study may limit generalizability; screening thresholds and access may vary by health system.
Future Directions: Evaluate cost-effectiveness and implementation of NT-proBNP–echo screening pathways; develop strategies for HFpEF risk stratification and early intervention in primary care.
BACKGROUND AND AIMS: Heart failure (HF) is a major global health burden, yet its true prevalence remains uncertain due to heterogeneous study designs and evolving diagnostic criteria. The Portuguese Heart Failure Prevalence Observational Study (PORTHOS) aimed to estimate the prevalence and phenotypic distribution of HF in community-dwelling adults aged ≥50 years in mainland Portugal. METHODS: PORTHOS was a cross-sectional, population-based study with a two-stage design. Stage 1 randomly selected community-dwelling individuals aged ≥50 years via structured interviews and point-of-care N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing. Individuals with NT-proBNP ≥125 pg/mL and/or a self-reported HF diagnosis, plus a random 5% of screen-negatives, proceeded to stage 2. This confirmatory stage included clinical assessment, electrocardiogram, and echocardiography. HF diagnosis required the presence of symptoms, NT-proBNP ≥125 pg/mL, and echocardiographic criteria. HF was defined as per the 2021 ESC and HFA-PEFF guidelines. RESULTS: Of 6189 participants, 2249 screened positive and 1136 were diagnosed with HF. The estimated HF prevalence was 16.54%, increasing with age (from 4.01% in 50-59 years old to 30.68% in those ≥70) and higher in females than males (21.00% vs 10.47%). Notably, 93.4% had HF with preserved ejection fraction (HFpEF), and 90% were previously undiagnosed. HFpEF was independently associated with older age, female sex, type 2 diabetes, atrial fibrillation, and dyslipidaemia. CONCLUSIONS: HF affects approximately one in six Portuguese adults aged ≥50 years, with HFpEF accounting for over 90% of cases, most previously undiagnosed. These findings support NT-proBNP-based screening combined with echocardiographic evaluation to improve early HF detection in ageing populations.