Cardiovascular therapeutic targets of sodium-glucose co-transporter 2 (SGLT2) inhibitors beyond heart failure DOI Creative Commons
Matteo Armillotta,

Francesco Angeli,

Pasquale Paolisso

et al.

Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: 270, P. 108861 - 108861

Published: April 15, 2025

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are oral antidiabetic agents that have shown significant improvements in cardiovascular and renal outcomes among patients with heart failure (HF), regardless of diabetic status, establishing them as a cornerstone therapy. In addition to glycemic control the osmotic diuretic effect, inhibition SGLT2 improves endothelial function vasodilation, optimizing myocardial energy metabolism preserving cardiac contractility. Moreover, may exhibit anti-inflammatory properties attenuate acute ischemia/reperfusion injury, thereby reducing infarct size, enhancing left ventricular function, mitigating arrhythmias. These pleiotropic effects demonstrated efficacy across various conditions, ranging from chronic coronary syndromes extending arrhythmias, valvular disease, cardiomyopathies, cardio-oncology, cerebrovascular disease. This review provides an overview current literature on potential mechanisms underlying effectiveness wide range diseases beyond HF.

Language: Английский

The Last Decade in Cardiac Amyloidosis DOI Creative Commons
Alberico Del Torto, Adam Ioannou, Sarah Cuddy

et al.

JACC. Cardiovascular imaging, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Cardiac amyloidosis represents a unique disease process characterized by amyloid fibril deposition within the myocardial extracellular space. Advances in multimodality cardiac imaging enable accurate diagnosis and facilitate prompt initiation of disease-modifying therapies. Furthermore, rapid advances have enriched understanding underlying pathogenesis, enhanced prognostication, resulted development imaging-based markers that reflect burden, which is increasing importance when assessing response to treatment. Whereas conventional therapies focused on reducing formation subsequent stabilization process, novel agents are being developed accelerate immune-mediated removal fibrils from heart. In this context, ability track changes burden over time paramount importance. Although advanced techniques shown efficacy tracking treatment response, future research improved precision through use artificial intelligence may augment detection earlier course

Language: Английский

Citations

4
Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Cardiovascular Outcomes in Transthyretin Amyloid Cardiomyopathy DOI

Stefano Byer,

Aravinthasamy Sivamurugan,

Udhayvir Singh Grewal

et al.

The American Journal of Cardiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

2
Efficacy of Acoramidis on All-Cause Mortality and Cardiovascular Hospitalization in Transthyretin Amyloid Cardiomyopathy DOI Creative Commons
Daniel P. Judge, Kevin Alexander, Francesco Cappelli

et al.

Journal of the American College of Cardiology, Journal Year: 2025, Volume and Issue: 85(10), P. 1003 - 1014

Published: March 1, 2025

Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed chronic disease associated with progressive heart failure that results in impaired quality of life, repeated hospitalizations, and premature death. Acoramidis a selective, oral transthyretin stabilizer recently approved by the U.S. Food Drug Administration for treatment ATTR-CM. In phase 3, randomized, double-blind study (ATTRibute-CM [Efficacy Safety AG10 Subjects With Amyloid Cardiomyopathy]), acoramidis was well tolerated showed clinical efficacy improving primary endpoint, hierarchical combination all-cause mortality (ACM), cardiovascular-related hospitalization (CVH), N-terminal pro-B-type natriuretic peptide level, 6-minute walk distance. The goal this to characterize on ACM CVH. ATTRibute-CM, participants ATTR-CM were randomized 2:1 receive hydrochloride (800 mg twice daily) or placebo 30 months. Efficacy analyses conducted modified intention-to-treat population (participants baseline estimated glomerular filtration rate ≥30 mL/min/1.73 m2). CVH composite first plotted using Kaplan-Meier curves summarized stratified Cox proportional hazards model. annualized frequency analyzed negative binomial regression Subgroup Of 632 treatment, 611 (97%) included (acoramidis, n = 409; placebo, 202). Compared reduced occurrence 35.9%; 50.5%; HR: 0.64; 95% CI: 0.50-0.83; P 0.0008) 26.7%; 42.6%; 0.60; 0.45-0.80; 0.0005), separating at month 3 continuing diverge through 30. Annualized compared 0.22; 0.45; relative risk ratio: 50%; 0.36-0.70; < 0.0001). consistent across subgroups. tolerated, no safety signals potential concern identified. ATTR-CM, vs early effect driven reduction (Efficacy Cardiomyopathy [ATTRibute-CM]; NCT03860935).

Language: Английский

Citations

2
Clinical Phenotype and Prognosis of Asymptomatic Patients With Transthyretin Cardiac Amyloid Infiltration DOI Creative Commons
Aldostefano Porcari, Yousuf Razvi, Francesco Cappelli

et al.

JAMA Cardiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 22, 2025

Importance Patients with transthyretin (ATTR) cardiac amyloid infiltration are increasingly diagnosed at earlier disease stages no heart failure (HF) symptoms and a wide range of infiltration. Objective To characterize the clinical phenotype natural history asymptomatic patients ATTR Design, Setting, Participants This cohort study analyzed data all 12 international centers for amyloidosis from January 1, 2008, through December 31, 2023. Inclusion criteria were infiltration, defined as an absence HF history, signs symptoms, diuretic therapy, plasma cell dyscrasia evidence myocardial uptake on bone scintigraphy. If was present, histologic confirmation required. Exposure Asymptomatic Main Outcomes Measures The primary outcomes all-cause cardiovascular (CV) mortality. secondary unplanned hospitalization, CV-related composite outcome CV mortality hospitalization. Results comprised 485 (mean [SD] age, 74.9 [9.9] years, 85.8% male, 112 [23.1%] hereditary amyloidosis), 369 (76.1%) having grade 2 or 3 116 (23.9%) 1 baseline. exhibited significantly more functional structural abnormalities vs uptake. At compared uptake, had greater development (54.3% [95% CI, 47.7%-61.3%] 23.1% 14.8%-35.1%]), outpatient initiation N-terminal pro-B-type natriuretic peptide progression (35.0% 28.0%-43.2%] 12.4% 6.3%-23.7%]), hospitalization (8.7% 5.9%-12.9%] 0%) (20.0% 15.7%-25.3%] 4.3% 1.6%-11.3%]). Over median follow-up 37 months (IQR, 20-64 months), death rate similar between uptake; however, those higher risk (unadjusted hazard ratio, 5.30; 95% 1.92-14.65). Conclusions Relevance shows that encompasses spectrum severity, experiencing increased events lower event predominantly non-CV These findings support use disease-modifying treatments in highlight need large-scale studies to assess their role

Language: Английский

Citations

1
Can Outpatient Worsening Heart Failure Serve as an Endpoint in Clinical Trials of Transthyretin Amyloidosis? DOI
Richard K. Cheng, Douglas Leedy, Frederick L. Ruberg

et al.

Journal of the American College of Cardiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Sodium‐glucose cotransporter 2 inhibitors and outcomes in transthyretin amyloid cardiomyopathy: Systematic review and meta‐analysis DOI Creative Commons
Paschalis Karakasis, Panagiotis Theofilis, Dimitrios Patoulias

et al.

European Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR‐CM) commonly leads to heart failure but has traditionally been an exclusion criterion in randomized clinical trials (RCTs) of sodium‐glucose cotransporter 2 inhibitors (SGLT2i); therefore, the effects these drugs this population remain undocumented. In light recent studies, meta‐analysis aimed investigate effect SGLT2i on prognosis patients with ATTR‐CM. Methods A comprehensive search Medline, Scopus, and Cochrane Library was conducted up November 17, 2024. Study selection, data extraction quality assessment were carried out independently by two investigators. Associations outcomes pooled using random‐effects meta‐analyses. Results total five studies (9766 participants, 4 propensity score‐matched) included. The use associated significant reductions all‐cause mortality [hazard ratio (HR) .54, 95% confidence interval (CI) .44–.66], cardiovascular (HR .39, CI .23–.65), major adverse events .71, .61–.83), hospitalizations (HFHs) .63, .52–.77) compared non‐use. odds cardiac arrhythmias significantly lower among users non‐users [odds (OR) .73, .65–.83]. Specifically, atrial fibrillation (AF) (OR .75, .62–.91), ventricular tachycardia .72, .59–.88), sudden arrest .50–.99). Conclusions SGLT2is may be a more favourable Adequately powered, long‐term RCTs are required validate available observational evidence.

Language: Английский

Citations

1
Sodium-Glucose Cotransporter 2 Inhibitor Use and Outcomes in Transthyretin Amyloid Cardiomyopathy DOI Creative Commons
Vikash Jaiswal, Muhammad Hanif, Yusra Mashkoor

et al.

JACC Advances, Journal Year: 2024, Volume and Issue: 3(12), P. 101405 - 101405

Published: Nov. 15, 2024

Language: Английский

Citations

8
Transthyretin cardiac amyloid: Broad heart failure phenotypic spectrum and implications for diagnosis DOI Creative Commons

Mileydis Alonso,

Radhika Neicheril,

Yosef Manla

et al.

ESC Heart Failure, Journal Year: 2024, Volume and Issue: 11(6), P. 3649 - 3655

Published: Aug. 24, 2024

Transthyretin cardiac amyloidosis (ATTR-CA) is most often associated with heart failure preserved ejection fraction (HFpEF). However, patients may present impaired systolic function at the time of diagnosis, which has not been widely investigated. We sought to explore prevalence various (HF) phenotypes and their clinical characteristics ATTR-CA diagnosis.

Language: Английский

Citations

5
Hereditary cardiac amyloidosis associated with a rare p.Ala101Val transthyretin mutation: a case description DOI Open Access

Shanshan Yuan,

Miao Zhang, Wei Liu

et al.

Quantitative Imaging in Medicine and Surgery, Journal Year: 2025, Volume and Issue: 15(3), P. 2625 - 2631

Published: Jan. 21, 2025

Language: Английский

Citations

0
Improving Long-term Outcomes in ATTR-CM DOI Creative Commons
Nowell M. Fine

JACC CardioOncology, Journal Year: 2025, Volume and Issue: 7(3), P. 294 - 296

Published: Feb. 11, 2025

Language: Английский

Citations

0