Biomedical subjects

Naveen L Pereira

Publications and source records attributed to Naveen L Pereira.

3 recordsLinked to original sources

PubMed2026

Incidence of Atrial and Ventricular Arrhythmias in Patients With Titin Truncating Variants Across the Ventricular Morphofunctional Phenotypic Spectrum.

BACKGROUND: Titin truncating variants (TTNtvs), the most common genetic cause of dilated cardiomyopathy (DCM), are over-represented in early-onset atrial fibrillation (AF) and unexplained sudden cardiac arrest/death (SCA/SCD), suggesting they can cause arrhythmias before development of overt ventricular cardiomyopathy. OBJECTIVES: This study sought to compare the incidence of atrial and ventricular arrhythmias (VAs) between TTNtv-positive patients with genotype-positive but phenotype-negative (G+/P-) disease, nondilated left ventricular cardiomyopathy (NDLVC), and DCM. METHODS: A retrospective review of 1,229 patients in our Arrhythmogenic/Dilated Cardiomyopathy Registry was used to identify those with pathogenic/likely pathogenic TTNtvs. Patients were classified as having G+/P- disease, NDLVC, or DCM using the 2023 European Society of Cardiology guideline for cardiomyopathies. The incidence of AF, sustained VA, appropriate defibrillator therapies, SCA, and SCD was ascertained from medical records. RESULTS: Among 253 TTNtv-positive patients (mean age of 45 ± 16 years; 59% male), 54 (21%) were G+/P-, 49 (20%) were NDLVC, and 150 (59%) were DCM. During a median follow-up of 3.8 years at our institution, new-onset AF was seen in 67 patients (26% of those at risk). There was no significant difference in survival from new-onset AF in patients with NDLVC (HR: 3.29; 95% CI: 0.71-15.3; P = 0.13), although DCM was associated with worse AF-free survival (HR: 4.86; 95% CI: 1.17-20.1; P = 0.03). New-onset VAs were seen in 44 (17%) patients during follow-up, including SCA in 12 (5%) patients. There was no association between NDLVC (HR: 0.71; 95% CI: 0.19-2.69; P = 0.62) and DCM (HR: 0.97; 95% CI: 0.37-2.54; P = 0.95) phenotypes compared with G+/P- patients. Cardiac transplantation was done in 14 (6%) patients, and 6 (2%) died of cardiac causes, including 2 cases of SCD. CONCLUSIONS: When stratified by morphofunctional phenotype, there was no difference in VAs across morphofunctional phenotypes in patients with TTNtvs. This highlights that patients with TTNtvs may be at risk of SCA/SCD even without overt ventricular cardiomyopathy. The risk of new-onset AF was highest in patients with DCM but was seen at all phenotypic stages during follow-up.

arrhythmia↗

PubMed2026

2025 Acute Coronary Syndrome Guideline: Missing the Boat on CYP2C19 Genotyping.

The 2025 American College of Cardiology/American Heart Association/American College of Emergency Physicians/National Association of Emergency Medical Services Physicians/Society for Cardiovascular Angiography & Interventions acute coronary syndrome guideline focuses on strategies to reduce bleeding risk with antiplatelet therapy yet lacks any recommendation related to CYP2C19 genotyping. The impact of CYP2C19 loss-of-function alleles on the effectiveness of clopidogrel is well documented, and although prasugrel and ticagrelor more effectively reduce the risk for atherothrombotic events compared with clopidogrel in patients with a CYP2C19 loss-of-function allele, clopidogrel reduces bleeding risk without an increase in atherothrombotic events compared with prasugrel or ticagrelor in those without a loss-of-function allele. Accordingly, an American Heart Association Scientific Statement supports CYP2C19 genetic testing before oral P2Y12 inhibitors are prescribed. This commentary summarizes the evidence in support of CYP2C19-guided P2Y12 inhibitor selection in the context of other 2025 acute coronary syndrome guideline recommendations and urges future guidelines to incorporate recommendations for CYP2C19 genotyping, especially for those at high bleeding risk.

Humans↗

PubMed2026

Novel association of NAV3 with dilated cardiomyopathy and its role in cardiac fibrosis.

A genome-wide association study (GWAS) identified neuron navigator 3 (NAV3) as a potential genetic determinant of myocardial recovery in dilated cardiomyopathy (DCM). This study aimed to understand its functional role in cardiac pathophysiology by leveraging omics approaches. Single-cell RNA-seq transcriptomic data from previously published adult human hearts indicate that NAV3 expression is highest in cardiac fibroblasts, suggesting its functional role in these cells. In vitro, stimulation of primary human ventricular cardiac fibroblasts with transforming growth factor β1 (TGF-β1) induced NAV3 expression in a dose and time-dependent manner. Small-interfering-RNA-mediated knockdown of NAV3 significantly attenuated TGF-β1-induced fibroblast activation, reducing the expression of α-smooth muscle actin (α-SMA), collagens, and fibronectin. RNA sequencing of NAV3-silenced fibroblasts, confirmed by Western blot, revealed upregulation of cell cycle regulators and downregulation of profibrotic markers, suggesting that NAV3 facilitates TGF-β1-induced cell cycle arrest and fibroblast-to-myofibroblast transition. Notably, NAV3 silencing did not alter canonical SMAD2/3 phosphorylation, implying a role for NAV3 in modulating fibrotic signaling through other pathways. Our findings provide functional and mechanistic insights into NAV3's novel role in cardiac fibrosis, showing that reduced NAV3 expression attenuates TGF-β1-mediated fibroblast activation by regulating cell cycle signaling. These results support further investigation of NAV3 as a potential modulator of cardiac fibrosis and myocardial recovery in DCM.NEW & NOTEWORTHY This study uncovers a previously unrecognized role for NAV3 in TGF-β1-driven cardiac fibroblast activation. We show that NAV3 facilitates profibrotic remodeling through noncanonical signaling and cell cycle arrest, independently of SMAD2/3. These findings position NAV3 as a novel regulator of fibroblast phenotype and a potential modulator of cardiac fibrosis.

Humans↗