Daily Cardiology Research Analysis
Analyzed 131 papers and selected 3 impactful papers.
Summary
Analyzed 131 papers and selected 3 impactful articles.
Selected Articles
1. Molecular mechanism leading to human coronary atherosclerosis assessed by proteomic analysis and RNA sequences.
Using 322 human coronary samples spanning normal to preclinical plaque, the authors defined four proteomic latent features that track early atherosclerosis, including marked mitochondrial biosynthetic decline and vascular unit activation before immune recruitment. Computational network mapping nominated transcriptional regulators, and manipulating MLXIPL in human arterial organoids produced predicted proteomic shifts, highlighting actionable early drivers.
Impact: This large, human-tissue multi-omics atlas reveals earliest molecular programs of coronary atherogenesis and functionally validates a master regulator, offering high-value targets for disease interception.
Clinical Implications: While not immediately practice-changing, the study prioritizes early targets (e.g., MLXIPL-regulated programs, mitochondrial pathways, vascular unit activation) for therapeutic development aimed at intercepting atherogenesis before immune recruitment.
Key Findings
- Identified four proteomic latent features (100 proteins each) tracking early molecular disease progression (FDR P < .01).
- Early changes showed dramatic decline in mitochondrial biosynthesis proteins and vascular unit activation (including pericytes).
- Neurovascular and neuroimmune modulation preceded characteristic immune cell recruitment of plaques.
- Single-cell coronary RNASeq validated latent features and master transcriptional regulators (all P < .01).
- Functional validation: MLXIPL manipulation in human arterial organoids induced expected expression shifts in two targeted latent features (P = .0003 and P < .00001).
- Despite no clinical disease, 56% of samples displayed morphologic preclinical atherosclerosis.
Methodological Strengths
- Large human coronary tissue biorepository (n=322) spanning normal to preclinical plaque.
- Integrated proteomics, RNA-Seq, dimensionality reduction/deconvolution with single-cell validation and organoid functional testing.
Limitations
- Cross-sectional human tissue with pseudo-time inference rather than longitudinal progression.
- Functional validation focused on one regulator (MLXIPL); translational path to therapies remains to be established.
Future Directions: Prospective validation in living human cohorts, perturbation of additional candidate regulators, and target engagement studies to develop early-interception therapies for coronary atherosclerosis.
BACKGROUND AND AIMS: Atherosclerosis results from cellular and extracellular changes in the arterial wall, preceded by molecular shifts that initiate disease and drive tissue conversion, yet these changes are not yet fully described. More data are needed concerning these early changes in the coronary artery molecular landscape that signify the initiation of atherosclerosis and the subsequent tissue pheno-conversion to atherosclerotic plaque. This report summarizes results from a large biorepository of human coronary artery tissue, applying state-of-the-art omics technology, advanced data analytic methods, and an arterial organoid model system to predict molecular dynamics and identify potential regulatory mechanisms that could interrupt molecular changes that contribute to the earliest stages of disease pathogenesis. The long-term goal of this effort is to identify and develop new therapies to further mitigate the persistently high burden of clinical coronary disease. METHODS: Mass spectrometry-based proteomic analysis and RNA sequencing (RNASeq) were used to analyse proximal coronary arterial samples from young adults who died of trauma with no ante mortem suspicion of coronary disease [n = 322, mean age (range): 34.1 years (15-59); sex: M-239, F-83; race: W-218, B-88, other-16]. Despite the absence of clinical disease, 56% of samples had morphologic evidence of pre-clinical atherosclerosis. Analyses of the proteomic data (n = 1900 proteins) using state-of-the-art dimensionality reduction and deconvolution techniques generated an estimate of molecular disease progression (e.g. pseudo-time) and identified selected proteomic latent features (LFs) (i.e. large groups of co-ordinated proteins) associated with its initiation and progression. Computational genomics, machine learning models, and multi-omic network mapping of these proteomic LFs and associated mRNA gene transcripts suggested potential transcriptional regulators which were subsequently confirmed in publicly available single-cell coronary artery data. The effects of one of the leading regulatory transcription factors (TFs), MLXIPL, predicted to regulate two LFs, were further validated in a human arterial cell organoid model system. RESULTS: Four proteomic LFs, composed of n = 100 signature proteins/LF, exhibited distinct patterns with respect to disease progression [false discovery rate (FDR) P < .01]. These LFs illuminate the earliest changes in the arterial proteome during tissue pheno-conversion from normal coronary artery to atherosclerotic plaque, including dramatic declines in mitochondrial energy biosynthesis proteins, evidence of vascular unit activation (including pericytes), and neurovascular and neuroimmune modulation (all FDR P < .01). These early changes preceded the expected immune cell recruitment and innate immune response characteristic of atherosclerotic plaque formation. Analysis of transcriptional regulatory networks identified from RNASeq data highlighted both known and novel TFs and master regulators of LF proteins that may drive the initial and early stages of disease progression. Publicly available single-cell RNASeq data from normal and atherosclerotic coronary arteries validated the LFs and several of their likely master transcriptional regulators (all P < .01); and manipulation of the levels of one of top regulatory TFs, MLXIPL, in human arterial cell organoids resulted in the expected changes in expression of the proteins associated with its two targeted LFs (P = .0003 and P < .00001, respectively). CONCLUSIONS: The unique nature of this human coronary biorepository with samples ranging from entirely normal to mature pre-clinical atherosclerotic plaque facilitated prediction of molecular disease progression and identification of several potential transcriptional regulators for further evaluation as potential novel targets to interrupt early initiation and progression of atherosclerotic coronary disease.
2. Intravascular Ultrasound-Guided Local Theranostics Enables Precise Treatment of Atherosclerotic Plaques.
A single IVUS-guided catheter integrates imaging and sonodynamic therapy using osteopontin-targeted, piezoelectric bismuth nanoparticles that accumulate in foam cells. Pulsed ultrasound parameters control ROS generation, inducing foam-cell apoptosis and plaque regression in preclinical models with minimal off-target effects, enabling precise, lesion-specific intravascular theranostics.
Impact: Introduces a clinically plausible, image-integrated intravascular theranostic platform that overcomes depth and targeting limitations of SDT, potentially transforming coronary plaque treatment.
Clinical Implications: If validated in humans, IVUS-guided piezo-sonodynamic therapy could provide lesion-specific coronary plaque regression with real-time monitoring, complementing or reducing reliance on systemic lipid-lowering and anti-inflammatory strategies.
Key Findings
- Developed an IVUS-guided catheter that integrates high-resolution imaging and localized sonodynamic therapy.
- Engineered osteopontin-targeted, piezoelectric bismuth nanoparticles that selectively accumulate in foam cells.
- Modulating pulse-repetition time and pulse width controlled ROS generation, inducing foam-cell apoptosis.
- In vitro and in vivo studies demonstrated plaque regression with minimal adverse effects.
- Real-time IVUS visualization ensured precise, lesion-specific energy delivery.
Methodological Strengths
- Theranostic integration of imaging and therapy in a single intravascular catheter.
- Systematic in vitro and in vivo validation with mechanistic control via ultrasound pulse parameters.
Limitations
- Preclinical models; human coronary safety, biodistribution, and long-term outcomes are unknown.
- Regulatory translation and manufacturing scalability of targeted nanoparticles remain to be addressed.
Future Directions: GLP toxicology, large-animal coronary studies, and first-in-human feasibility to assess safety, target engagement, and plaque biology endpoints; optimization of nanoparticle pharmacokinetics and catheter deliverability.
Although sonodynamic therapy (SDT) has shown promise in reducing atherosclerotic plaque burden, its clinical application remains confined to superficial lesions, as deep-seated plaques such as those in coronary arteries lack precise imaging guidance and lesion-specific energy delivery. Here, we report an intravascular ultrasound (IVUS)-guided SDT strategy that integrates high-resolution imaging and precise treatment within a single catheter system. Osteopontin (OPN)-targeted bismuth-based nanoparticles (BSNPs), endowed with piezoelectricity through defect-induced symmetry breaking, selectively accumulate in foam cells. Pulsed ultrasound emitted by the IVUS catheter triggers BSNPs to generate reactive oxygen species (ROS) through the modulation of pulse-repetition time (PRT) and pulse width (PW), thereby inducing foam cell apoptosis and promoting plaque regression. With IVUS guidance, the SDT process can be visualized in real time, ensuring precise lesion-specific treatment. Systematic in vitro and in vivo studies demonstrate the effective antiatherosclerotic effect with minimal adverse effects. This imaging-integrated piezo-sonodynamic platform establishes a multifunctional catheter-based ultrasound theranostic strategy, providing a precise and clinically translatable approach for treating atherosclerosis.
3. Pulsed Field Ablation versus Thermal Ablation for Pulmonary Vein Isolation: A Network Meta-Analysis of Randomized Controlled Trials.
Across 18 RCTs (n=4,162), PFA reduced 12-month atrial tachyarrhythmia recurrence versus radiofrequency (RR 1.48) and cryoballoon (RR 1.43), with similar major complication rates. PFA had the shortest procedural time, while RF had less fluoroscopy time, supporting PFA as an efficacious and efficient first-line energy for pulmonary vein isolation.
Impact: Synthesizes RCT evidence indicating superior efficacy and efficiency of PFA compared with thermal energies for first-time AF ablation, informing technology selection and workflow optimization.
Clinical Implications: Operators may preferentially adopt PFA for first-time PVI given lower recurrence and shorter procedure times with comparable safety; fluoroscopy exposure may be lower with RF, warranting radiation-sparing strategies in PFA workflows.
Key Findings
- Included 18 RCTs with 4,162 patients undergoing first-time PVI.
- Thermal energies had higher 12-month ATA recurrence versus PFA (RFA RR 1.48; CBA RR 1.43; LBA RR 1.29, non-significant).
- PFA showed the shortest procedural time among energies; RF had lower fluoroscopy time.
- Major periprocedural complications were similar across energy sources.
- Findings were consistent in paroxysmal-only and contemporary-technology subgroups.
Methodological Strengths
- Network meta-analysis restricted to RCTs with PRISMA-compliant methods and registration.
- Pre-specified subgroup analyses (paroxysmal AF and contemporary technologies) to test robustness.
Limitations
- Indirect comparisons across heterogeneous devices and operator experience; lack of patient-level data.
- Follow-up limited to 12 months; long-term durability and lesion quality require further study.
Future Directions: Head-to-head RCTs with standardized endpoints, longer follow-up, and patient-level cost-effectiveness; studies optimizing PFA workflows to reduce fluoroscopy exposure.
BACKGROUND AND AIMS: Pulsed field ablation (PFA) has recently emerged as a promising alternative to conventional energy sources (ES) for atrial fibrillation (AF) ablation. However, comparative data between PFA and other ES-such as radiofrequency (RFA), cryoballoon (CBA), and laser balloon ablation (LBA)-remain limited.This network meta-analysis (CRD420251054760) aimed to compare outcomes of PFA versus thermal ES for AF ablation. METHODS: A systematic network metanalysis using PubMed, Cochrane and EMBASE from inception to March 2026 was performed. Randomized controlled trials comparing different ES in first-attempt pulmonary vein isolation were included. Data extraction was performed according to PRISMA guidelines. The primary outcome was the recurrence of any sustained atrial tachyarrhythmia (ATA) at 12-month follow-up. Safety and efficiency outcomes were also compared among groups. RESULTS: We included 18 studies, encompassing 4,162 patients. Compared to PFA, thermal ablation technologies showed a higher risk of ATA recurrence at 12-month follow-up (RFA: RR of 1.48 (95% CI 1.10-2.00); CBA: 1.43 (95% CI 1.07-1.92); LBA: RR 1.29 (CI 95% 0.84; 1.98)). PFA exhibited lowest procedural time among transcatheter ES, whereas RFA displayed a significantly lower fluoroscopy time. No significant differences were recorded for major periprocedural complications. A subgroup analysis restricted to studies involving only paroxysmal AF patients, as well as those employing contemporary technologies, yielded consistent findings. CONCLUSIONS: The present data indicate that, in patients undergoing a first transcatheter AF ablation, PFA may be associated with favourable efficacy and procedural efficiency compared with traditional thermal technologies, while showing a broadly comparable safety profile.