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.
Coronary endothelial dysfunction plays a key role in the pathogenesis of acute coronary syndromes. During myocardial infarction (MI), activated platelets release prothrombotic and proinflammatory factors, contributing to vascular injury and dysfunction. To investigate platelet-mediated endothelial dysfunction, endothelial cells (ECs) were treated with platelet-released factors from patients with MI and non-MI controls undergoing coronary angiography. RNA sequencing revealed that MI platelets induced EC mi
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.
BACKGROUND: Acute heart failure (AHF) is a severe clinical syndrome associated with high morbidity and mortality. Effective management of congestion is a primary treatment goal and often requires hospitalisation. While loop-diuretics remain the cornerstone of AHF therapy, the optimal combination of diuretics to an effective decongestion remains uncertain. This systematic review aims to evaluate the efficacy and safety of various diuretic combinations compared with usual care in AHF patients. METHODS: The search was conducted across the databases: Medline, Embase, Latin American and Caribbean Health Sciences Literature, Web of Science, Scopus and The Cochrane Central Register of Controlled Trials. Network meta-analysis was used to compare the relative efficacy of different diuretic combinations. Trial sequential analysis (TSA) was conducted to evaluate the sufficiency of cumulative evidence for definitive conclusions. Risk of bias was assessed using the Cochrane Risk of Bias tool for randomised trials V.2. Statistical heterogeneity was evaluated via visual inspection of forest plots through the
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.
INTRODUCTION AND OBJECTIVES: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve outcomes in heart failure (HF), but their role in patients undergoing transcatheter aortic valve implantation (TAVI) remains unclear. A recent randomized trial (DapaTAVI) showed reduced HF hospitalizations with SGLT2i post-TAVI, but effects on mortality and broader outcomes are unknown. METHODS: Using the TriNetX Research Network, we conducted a multicenter retrospective cohort study of adults with HF who underwent TAVI between 2015 and 2025. Patients prescribed SGLT2i within 30 days of TAVI were 1:1 propensity score-matched to nonusers. The primary outcome was all-cause mortality; secondary outcomes included hospitalizations, myocardial infarction, stroke, arrhythmias, and renal events. RESULTS: Among 58 193 TAVI recipients, 3022 SGLT2i users were matched to 3022 nonusers. SGLT2i use was associated with significantly lower mortality at 3 months (3.5% vs 4.9%; HR, 0.71), 6 months (5.0% vs 8.1%; HR, 0.61), 12 months (7.3% vs 10.5%; HR, 0.71), and 5 years (10.7% vs 20.6%; HR, 0.59; all P < .01). SGLT2i users also had fewer hospital or emergency room visits and a lower 5-year incidence of myocardial infarction (12.0% vs 14.4%; OR, 0.81, P = .007). Stroke incidence was lower at 6 months (4.8% vs 6.1%; P = .041) but was not sustained long term. Renal and arrhythmic outcomes were similar between groups. CONCLUSIONS: SGLT2i use in patients with HF undergoing TAVI was associated with reduced mortality and fewer adverse cardiovascular events. These findings support the integration of SGLT2i into post-TAVI management strategies.