Daily Cardiology Research Analysis
Analyzed 143 papers and selected 3 impactful papers.
Summary
Analyzed 143 papers and selected 3 impactful articles.
Selected Articles
1. Pyruvate metabolism enzyme Dlat induces mitochondria protein hyperacetylation to limit fatty acid oxidation in the HFpEF heart.
This mechanistic study identifies Dlat as a mitochondrial transacetylase that hyperacetylates FAO enzymes (including HADHA K728), suppressing fatty acid oxidation and worsening HFpEF phenotypes. Dlat knockdown reverses FAO inhibition and ameliorates cardiac metabolic and functional abnormalities, linking protein hyperacetylation causally to HFpEF.
Impact: It reveals a previously unrecognized enzymatic driver of mitochondrial protein hyperacetylation in HFpEF, providing a concrete molecular target and a mechanistic bridge between acetylation and metabolic failure.
Clinical Implications: While preclinical, targeting Dlat-mediated acetylation or restoring FAO could open therapeutic avenues for HFpEF, a condition with limited disease-modifying options.
Key Findings
- HFpEF hearts exhibit pronounced mitochondrial protein hyperacetylation enriched in the FAO pathway.
- Dlat functions as a mitochondrial transacetylase that directly acetylates FAO enzymes; Dlat increases HADHA K728 acetylation, inactivating HADHA.
- Dlat overexpression worsens lipid metabolic derangements and cardiac phenotype, whereas Dlat knockdown rescues FAO and mitigates HFpEF features.
Methodological Strengths
- Integrated in vivo and in vitro validation with site-specific acetylation (HADHA K728) mapping
- Mechanistic causality supported by gain- and loss-of-function of Dlat linked to metabolic and phenotypic rescue
Limitations
- Preclinical models may not fully recapitulate human HFpEF comorbidities and heterogeneity
- Translational relevance of targeting Dlat requires pharmacologic tools and human validation
Future Directions: Develop selective Dlat modulators; verify Dlat–acetylome signatures and FAO restoration in human HFpEF tissues; test therapeutic modulation in large-animal models and early-phase trials.
Increased protein acetylation is frequently observed in the failing heart, including in hearts with heart failure with preserved ejection fraction (HFpEF). However, its role in the pathogenesis of HFpEF remains insufficiently investigated. Here, we found that HFpEF hearts displayed significantly protein hyperacetylation, which were predominantly localized to mitochondria and particularly enriched in fatty acid oxidation (FAO) pathway. Notably, Dlat, a pyruvate metabolism enzyme, was identified as the key tr
2. Cardiac amyloidosis across the spectrum of left ventricular function: multimodal functional and prognostic insights.
In 2244 cardiac amyloidosis patients, 39% presented with HFmrEF/HFrEF. A decision tree combining LVEF, GLS, and cardiac index defined four prognostic strata with distinct 4-year mortality risks, outperforming LVEF alone and supporting multimodal imaging for individualized management.
Impact: Provides robust, externally validated evidence that multimodal functional parameters refine prognosis beyond LVEF across amyloidosis phenotypes.
Clinical Implications: Adopt routine GLS and cardiac index assessment alongside LVEF in cardiac amyloidosis to enhance risk stratification and guide timing/intensity of disease-modifying therapies.
Key Findings
- 39% of CA patients presented with HFmrEF or HFrEF despite CA’s HFpEF association.
- LVEF correlated only moderately with GLS and weakly with cardiac index, indicating complementary information.
- A decision tree integrating LVEF, GLS, and CIx yielded four prognostic groups with HRs for 4-year mortality from 1.6 to 3.7; findings were externally validated.
Methodological Strengths
- Large, phenotype-diverse cohort with external validation
- Multimodal imaging integration and decision tree modeling with time-to-event analysis
Limitations
- Observational design with potential residual confounding
- Center-specific practices may influence imaging acquisition and measurements
Future Directions: Prospective validation of the LVEF–GLS–CIx algorithm and integration with biomarkers/genetics to build individualized treatment pathways.
BACKGROUND: Although cardiac amyloidosis (CA) is often considered to be a cause of heart failure with preserved ejection fraction (HFpEF), many patients present with mildly reduced (HFmrEF) or reduced ejection fraction (HFrEF). Recognising CA across this spectrum is essential for diagnosis and risk stratification. METHODS: We studied 2244 patients with CA (557 light chain amyloidosis, 392 hereditary transthyretin amyloidosis, 1137 wild-type transthyretin amyloidosis) at the French national reference centre. Left ventricular ejection fraction (LVEF) was classified according to European Society of Cardiology guidelines. We evaluated the prognostic relevance of LVEF and its interaction with global longitudinal strain (GLS) and cardiac index (CIx). Survival was assessed with a Kaplan-Meier analysis, and a decision tree combined LVEF, GLS and CIx. Our findings were confirmed externally in an independent, French validation cohort. RESULTS: Although HFpEF was the most common phenotype, 39% of patients presented with HFmrEF or HFrEF. The survival time varied with the phenotype; the median was 30 months in HFrEF, 40 months in HFmrEF and was not reached in HFpEF. LVEF correlated moderately with GLS and weakly with CIx. A decision tree integrating LVEF, GLS and CIx identified four prognostic groups with HRs for 4-year mortality ranging from 1.6 to 3.7. CONCLUSIONS: CA affects the full spectrum of LVEF phenotypes. The integration of LVEF, GLS and CIx improves prognostic stratification and argues in favour of a multimodal imaging approach for early diagnosis and individualised management.
3. Left-sided heart failure determines outcomes in patients with severe tricuspid regurgitation undergoing percutaneous repair.
In 1,773 patients undergoing tricuspid TEER, left-sided HF phenotypes strongly influenced 2-year mortality and procedural success. While success (TR ≤ moderate) improved outcomes across all phenotypes, prognostic drivers differed (RV function in HFmrEF/HFrEF; right-sided pressures in HFpEF), supporting phenotype-specific selection and follow-up.
Impact: Provides large-scale, practice-informing evidence that HF phenotype stratification is crucial for outcome prediction after tricuspid TEER and that success benefits all but with time-varying effects.
Clinical Implications: Incorporate LVEF and hemodynamic phenotyping (PCWP) to guide TEER candidacy and tailor surveillance, focusing on RV function in HFrEF/HFmrEF and right-sided pressures in HFpEF.
Key Findings
- HF phenotypes distribution: 30% HFmrEF/HFrEF, 44% HFpEF, 26% non-overt left-sided HF in T-TEER candidates.
- Procedural success (TR ≤ moderate) highest in non-overt left-sided HF (87%) and lowest in HFmrEF/HFrEF (78%).
- 2-year mortality varied by phenotype (25.0% HFmrEF/HFrEF; 20.3% HFpEF; 13.1% non-overt), with phenotype-specific predictors of survival.
Methodological Strengths
- Large multicenter registry with predefined phenotypic stratification and 2-year outcomes
- Clinically meaningful endpoints and analysis of procedural success across phenotypes
Limitations
- Observational, non-randomized design with potential selection and treatment biases
- Procedure techniques and aftercare likely varied across centers
Future Directions: Prospective studies to test phenotype-guided selection and management algorithms; incorporate RV-pulmonary coupling and imaging biomarkers to refine risk.
AIMS: Tricuspid regurgitation (TR) frequently coexists with left-sided heart failure (HF). Tricuspid valve transcatheter edge-to-edge repair (T-TEER) has emerged as a treatment for severe TR, yet the prognostic role of coexisting HF phenotypes remains unclear. METHODS AND RESULTS: In the EuroTR registry, we assessed the impact of HF subtypes on 2-year all-cause mortality after T-TEER. Patients were stratified by left ventricular ejection fraction (LVEF) into reduced/mildly reduced (HFmrEF/HFrEF <50%) and preserved (≥50%). Those with preserved LVEF were further divided by pulmonary capillary wedge pressure (PCWP) into HFpEF (>15 mmHg) and non-overt left-sided HF (≤15 mmHg). Among 1,773 patients, 30% had HFmrEF/HFrEF, 44% HFpEF, and 26% non-overt left-sided HF. Procedural success (TR ≤moderate) was highest in non-overt left-sided HF (87%) and lowest in HFmrEF/HFrEF (78%). Symptom burden improved across all groups (p<0.001). Estimated 2-year mortality was 25.0% in HFmrEF/HFrEF, 20.3% in HFpEF, and 13.1% in non-overt left-sided HF. Procedural success was associated with improved outcomes in all groups (p<0.01). Among successfully treated patients, survival was comparable between HFmrEF/HFrEF and HFpEF at 1-year but better in HFpEF at 2-years (p=0.027). Predictors of survival differed by phenotype: right ventricular function for HFmrEF/HFrEF, right-sided pressures for HFpEF, and baseline TR severity for non-overt left-sided HF. CONCLUSION: Consideration of left-sided pathologies in patients with significant TR is important as outcomes and predictors for survival differ. Across HF phenotypes, procedural success is associated with survival but the prognostic impact of TR reduction may unfold over time especially in HFpEF.