Atrial Fibrosis in Atrial Fibrillation: Mechanistic Insights, Diagnostic Challenges, and Emerging Therapeutic Targets

International Journal of Molecular Sciences, Год журнала: 2024, Номер 26(1), С. 209 - 209

Опубликована: Дек. 30, 2024

Atrial fibrosis is a hallmark of atrial cardiomyopathy and plays pivotal role in the pathogenesis fibrillation (AF), contributing to its onset progression. The mechanisms underlying are multifaceted, involving stretch-induced fibroblast activation, oxidative stress, inflammation, coagulation pathways. Variations types-reactive replacement fibrosis-are influenced by patient-specific factors such as age, sex, comorbidities, complicating therapeutic approaches. heterogeneity leads distinct electrophysiological abnormalities that promote AF via reentrant activity enhanced automaticity mechanisms. Despite advancements imaging, late gadolinium enhancement CMR electroanatomical mapping, challenges accurately quantifying persist. Emerging strategies include antifibrotic agents targeting renin-angiotensin-aldosterone system, novel pathways like TGF-β signaling, cardio-metabolic drugs SGLT2 inhibitors GLP-1 receptor agonists. Innovative interventions, including microRNA modulation lipid nanoparticle-based therapies, show promise but require validation. Knowledge gaps remain correlating clinical outcomes with patterns optimizing diagnostic tools. Future research should focus on precise phenotyping, integrating advanced imaging molecular biomarkers, conducting robust trials evaluate therapies' efficacy reducing burden related complications.

Язык: Английский

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Mitigating Increased Cardiovascular Risk in Patients with Obstructive Sleep Apnea Using GLP-1 Receptor Agonists and SGLT2 Inhibitors: Hype or Hope?

Biomedicines, Год журнала: 2024, Номер 12(11), С. 2503 - 2503

Опубликована: Ноя. 1, 2024

Obstructive sleep apnea (OSA) is a prevalent condition associated with increased cardiovascular risk, particularly in individuals comorbid obesity and type 2 diabetes (T2D). Despite the widespread use of continuous positive airway pressure (CPAP) for OSA management, adherence remains suboptimal, CPAP has not consistently demonstrated reductions surrogate events. Recently, attention focused on glucagon-like peptide-1 receptor agonists (GLP-1RAs) sodium-glucose cotransporter-2 (SGLT2) inhibitors as potential therapeutic agents mitigating risk patients. These agents, originally developed T2D have pleiotropic effects, including significant weight loss, blood reduction, amelioration endothelial dysfunction arterial stiffness, along anti-inflammatory benefits, which may be beneficial OSA. Emerging clinical evidence suggests that GLP-1RAs SGLT2 can reduce severity improve daytime sleepiness, potentially reversing adverse effects observed This review explores pathophysiological mechanisms linking disease evaluates roles addressing Further research, long-term trials, necessary to establish effectiveness these therapies reducing events improving patients' reported outcomes this population.

Язык: Английский

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Effect of Glucagon-like Peptide-1 Receptor Agonism on Aortic Valve Stenosis Risk: A Mendelian Randomization Analysis

Journal of Clinical Medicine, Год журнала: 2024, Номер 13(21), С. 6411 - 6411

Опубликована: Окт. 26, 2024

Background: Aortic valve repair is currently the only effective treatment for calcific aortic stenosis (CAVS), as no pharmacological therapies exist to prevent or slow its progression. Recent promising results showed that glucagon-like peptide-1 (GLP-1) attenuates calcification of interstitial cells. Therefore, we conducted a two-sample Mendelian randomization analysis investigate effect GLP-1 receptor agonism (GLP-1Ra) on risk CAVS. Methods: The inverse variance weighted (IVW) method was used obtain primary causal inference, and several sensitivity analyses, including MR-Egger, were performed assess robustness results. Results: Based IVW estimates, GLP-1Ra neutral CAVS (odds ratio [OR] per 1 mmol/mol decrease in glycated hemoglobin = 0.87, 95% CI [0.69, 1.11], p 0.259; I2 4.5%, Cohran’s Q 2.09, heterogeneity 0.35; F statistic 16.8). A non-significant also derived by analyses. No evidence horizontal pleiotropy identified. Conclusions: not significantly associated with Furthermore, pragmatically designed studies are required evaluate clinical course different patient subgroups.

Язык: Английский

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Treatment of obesity-related HFpEF: a STEP closer to the SUMMIT

Future Cardiology, Год журнала: 2025, Номер unknown, С. 1 - 4

Опубликована: Март 7, 2025

Язык: Английский

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Cardiometabolic Phenotype in HFpEF: Insights from Murine Models

Biomedicines, Год журнала: 2025, Номер 13(3), С. 744 - 744

Опубликована: Март 18, 2025

Heart failure with preserved ejection fraction (HFpEF) remains a significant challenge in modern healthcare. It accounts for the majority of heart cases and their number worldwide is steadily increasing. With its high prevalence substantial clinical impact, therapeutic strategies HFpEF are still inadequate. This review focuses on cardiometabolic phenotype which characterised by such conditions as obesity, type 2 diabetes mellitus, hypertension. Various murine models that mimic this discussed. Each model’s pathophysiological aspects, namely inflammation, oxidative stress, endothelial dysfunction, changes cardiomyocyte protein function, myocardial metabolism alterations examined detail. Understanding these can provide insight into mechanisms underlying aid development effective interventions.

Язык: Английский

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An international modified Delphi consensus study on the optimal diagnosis and treatment of patients with HFpEF

Current Medical Research and Opinion, Год журнала: 2025, Номер unknown, С. 1 - 17

Опубликована: Март 18, 2025

Objective The global burden of HFpEF is high and, despite developments in available therapies, patient outcomes have not improved significantly. This study aimed to explore the optimal approaches diagnosis and treatment patients with develop recommendations on how guideline directed medical therapy can be introduced a more equitable universal manner.

Язык: Английский

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Clonal Hematopoiesis of Indeterminate Potential and Atrial Fibrillation: Insights into Pathophysiology and Clinical Implications

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2739 - 2739

Опубликована: Март 18, 2025

Clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a novel risk factor for cardiovascular diseases. CHIP is characterized by the expansion hematopoietic stem cell clones harboring somatic mutations in genes such TET2, DNMT3A, and ASXL1, which are implicated inflammation, atrial remodeling, hypercoagulability. These foster pro-inflammatory pro-thrombotic environment conducive to arrhythmogenesis, thereby linking development progression fibrillation (AF). Mechanistic insights indicate that contributes fibrosis, disrupts calcium signaling, exacerbates oxidative stress, all heighten susceptibility AF. Clinical studies, including epidemiological Mendelian randomization analyses, further support association between an increased both incident progressive AF, with specific TET2 ASXL1 identified significant contributors. Additionally, been linked adverse outcomes elevated rates heart failure, thromboembolism, mortality. Understanding CHIP’s role AF pathophysiology offers opportunities precision medicine approaches, providing avenues early intervention targeted treatment. This review synthesizes current mechanistic clinical evidence on emphasizes its biomarker stratification, explores emerging therapeutic strategies targeting CHIP-associated pathways.

Язык: Английский

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Treatment options for heart failure in individuals with overweight or obesity: a review

Future Cardiology, Год журнала: 2025, Номер unknown, С. 1 - 15

Опубликована: Март 18, 2025

Obesity and heart failure are interlaced global epidemics, each contributing to significant morbidity mortality. is not only a risk-factor for failure, but also complicates its management, by distinctive pathophysiological mechanisms cumulative comorbidities, requiring tailored treatment plan. To present current options in individuals with overweight/obesity, emphasizing available pharmacological therapies, non-pharmacological strategies, the management of related comorbidities. We conducted comprehensive literature review regarding results treatments including cornerstone interventions as well emerging therapeutic options. Specific drug classes, angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, sodium-glucose cotransporter-2 have demonstrated consistent efficacy irrespective body mass index, while diuretics remain key fluid management. Glucagon-like peptide-1 agonists shown promising improving relevant outcomes warrant further research. Non-pharmacological approaches, weight-loss strategies lifestyle modifications, improve symptoms, exercise tolerance quality life. Managing overweight/obesity requires multidisciplinary, individualized approach integrating Emerging therapies preventive arise address unique challenges this population provide improved outcomes.

Язык: Английский

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GLP-1 Receptor Agonists and Myocardial Perfusion: Bridging Mechanisms to Clinical Outcomes

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 3050 - 3050

Опубликована: Март 26, 2025

Coronary microvascular dysfunction (CMD) is a key contributor to myocardial ischemia and adverse cardiovascular outcomes, particularly in individuals with metabolic disorders such as type 2 diabetes (T2D). While conventional therapies primarily target epicardial coronary disease, effective treatments for CMD remain limited. Glucagon-like peptide-1 receptor (GLP-1R) agonists have emerged promising agents benefits extending beyond glycemic control. Preclinical clinical evidence suggests that GLP-1R activation enhances function through mechanisms including improved endothelial function, increased nitric oxide bioavailability, attenuation of oxidative stress, reduced vascular inflammation. Moreover, been shown improve blood flow, perfusion reserve, high-risk populations. Despite these findings, inconsistencies across studies due variability patient populations, study designs, imaging methodologies. This review summarizes current on the role perfusion, bridging mechanistic insights outcomes. Further large-scale, well-designed trials are needed clarify their long-term impact microcirculation explore potential targeted CMD.

Язык: Английский

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Obesity-Related Phenotype of Heart Failure With Preserved Ejection Fraction: A Comprehensive Review

Cureus, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome an obesity-related phenotype gaining prominence amid the global obesity epidemic. This review explores distinct pathophysiological mechanisms, diagnostic challenges, and management strategies associated obesity-induced HFpEF. Obesity contributes to HFpEF through several key including increased blood volume, myocardial hypertrophy fibrosis, systemic inflammation, metabolic dysregulation. These factors collectively exacerbate diastolic dysfunction elevate left ventricular filling pressures, hallmark features of Diagnosing in obese patients particularly challenging due overlapping comorbidities such as hypertension diabetes, well reduced reliability traditional biomarkers N-terminal pro-B-type natriuretic peptide. Advanced imaging techniques are crucial assessing remodeling. Managing requires comprehensive approach. Lifestyle modifications, weight loss exercise, form cornerstone treatment, complemented by pharmacological therapies sodium-glucose cotransporter 2 inhibitors mineralocorticoid receptor antagonists. Optimizing comorbidity essential, while emerging targeting dysfunction, alongside precision medicine approaches, offer promising future advancements. underscores need for inclusive trials personalized treatment improve outcomes A deeper understanding this developing targeted interventions that enhance patient care quality life. Integrating these insights into practice can help optimize accuracy, refine therapeutic guide risk stratification better management.

Язык: Английский

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