Daily Cardiology Research Analysis
Three studies advance cardiology across mechanisms, therapeutics, and diagnostics: (1) a translational study links platelet-derived CCL3/CCR5 signaling to endothelial mitochondrial dysfunction in myocardial infarction and associates circulating CCL3 with future MACE; (2) a network meta-analysis of 35 RCTs shows diuretic combinations (notably with acetazolamide) improve decongestion in acute heart failure without mortality benefit; (3) a large real-world cohort finds SGLT2 inhibitors after TAVI i
Summary
Three studies advance cardiology across mechanisms, therapeutics, and diagnostics: (1) a translational study links platelet-derived CCL3/CCR5 signaling to endothelial mitochondrial dysfunction in myocardial infarction and associates circulating CCL3 with future MACE; (2) a network meta-analysis of 35 RCTs shows diuretic combinations (notably with acetazolamide) improve decongestion in acute heart failure without mortality benefit; (3) a large real-world cohort finds SGLT2 inhibitors after TAVI in heart failure are associated with lower mortality and fewer adverse cardiovascular events.
Research Themes
- Platelet–endothelium crosstalk and mitochondrial dysfunction in MI
- Optimizing decongestion strategies in acute heart failure
- SGLT2 inhibitors in structural heart disease (post-TAVI heart failure)
Selected Articles
1. Platelets induce endothelial cell mitochondrial dysfunction in myocardial infarction.
Platelet releasates from MI patients disrupted endothelial mitochondrial potential and networks. Multi-omics identified CCL3 upregulation in MI platelets as a key mediator; CCR5 blockade attenuated these effects. In a cohort of 261 patients with established CVD, higher circulating CCL3 associated with incident MACE, linking platelet activation to endothelial dysfunction and outcomes.
Impact: Defines a novel platelet–endothelium mitochondrial injury axis via CCL3/CCR5 with translational potential and prognostic relevance.
Clinical Implications: Suggests CCL3/CCR5 as a therapeutic target to mitigate coronary endothelial damage in MI and highlights circulating CCL3 as a potential risk stratification biomarker.
Key Findings
- MI platelet releasates decreased endothelial mitochondrial membrane potential and disrupted mitochondrial networks.
- CCL3 was upregulated in MI platelets and mediated endothelial mitochondrial dysfunction; CCR5 blockade attenuated effects.
- Higher circulating CCL3 levels predicted incident major adverse cardiovascular events in an independent cohort (n=261).
Methodological Strengths
- Integrative multi-omics combining platelet and endothelial transcriptomics with functional mitochondrial assays
- Independent clinical cohort linking CCL3 levels to incident outcomes and receptor-blockade mechanistic validation
Limitations
- Causality for clinical outcomes not established without intervention trials
- Size of clinical association cohort (n=261) limits subgroup analyses and external generalizability
Future Directions: Test CCR5 antagonism or CCL3 neutralization to prevent microvascular injury in MI, and evaluate CCL3-guided risk stratification in larger prospective cohorts.
2. Combinations of diuretics for acute heart failure: a systematic review with network meta-analysis and trial sequential analysis.
Across 35 RCTs (n=11,743), combination diuretic therapy improved short-term decongestion (greater weight loss/urine output), with combinations including acetazolamide showing the largest effects. No reduction was observed in all-cause mortality, SAEs, readmissions, or kidney failure; TSA supported lack of mortality benefit with current evidence.
Impact: Provides high-level evidence clarifying that decongestion gains do not translate into mortality benefits, guiding pragmatic AHF pharmacotherapy and trial design.
Clinical Implications: Supports using combination diuretics (notably acetazolamide) to accelerate decongestion while setting realistic expectations regarding survival; emphasizes the need to individualize therapy and monitor for safety without expecting mortality reductions.
Key Findings
- Network meta-analysis of 35 RCTs (11,743 patients) showed combination diuretics improved short-term decongestion metrics.
- Acetazolamide-containing regimens produced greater weight loss and diuresis than usual care.
- No significant effect on all-cause mortality, SAEs, hospital readmissions, or kidney failure; TSA indicated insufficient evidence for mortality reduction.
Methodological Strengths
- Comprehensive network meta-analysis with trial sequential analysis across 35 randomized trials
- Robust risk-of-bias assessment using RoB 2.0 and evaluation of heterogeneity
Limitations
- Outcome focus on short-term decongestion; trials underpowered for mortality endpoints
- Indirect comparisons inherent to NMA and variability in dosing and patient selection
Future Directions: Design adequately powered RCTs to test whether targeted decongestion strategies (e.g., acetazolamide-guided) improve patient-centered outcomes and to identify phenotypes that benefit most.
3. Impact of SGLT2 inhibitors on long-term outcomes in TAVI patients with heart failure: a propensity-matched analysis.
In a propensity-matched multicenter cohort (3,022 vs 3,022), SGLT2 inhibitor initiation within 30 days post-TAVI in patients with heart failure was associated with lower all-cause mortality at 3 months, 6 months, 12 months, and 5 years, fewer hospital/ER visits, and lower 5-year myocardial infarction. Stroke reduction was transient; renal and arrhythmic outcomes were similar.
Impact: Extends the benefits of SGLT2 inhibitors to a high-risk structural heart disease population with signals for survival benefit, informing post-TAVI management.
Clinical Implications: Consider early SGLT2 inhibitor initiation after TAVI in heart failure patients, while acknowledging observational design and the need to individualize therapy and monitor for tolerability.
Key Findings
- Propensity-matched analysis (n=6,044) showed lower all-cause mortality with SGLT2 inhibitors at 3, 6, 12 months and 5 years post-TAVI.
- SGLT2 inhibitor users had fewer hospital/ER visits and reduced 5-year myocardial infarction; stroke reduction was not sustained long-term.
- No significant differences in renal or arrhythmic outcomes between groups.
Methodological Strengths
- Large multicenter real-world dataset with 1:1 propensity score matching
- Multiple time-point survival analyses and assessment of broad cardiovascular outcomes
Limitations
- Retrospective observational design with potential residual confounding and treatment selection bias
- Medication adherence, dosing, and cause-specific mortality not fully captured
Future Directions: Prospective randomized trials in post-TAVI heart failure populations to confirm mortality benefit, define optimal timing, and evaluate safety and subgroups.