Discovery of Titin and Its Role in Heart Function and Disease

Circulation Research, Год журнала: 2025, Номер 136(1), С. 135 - 157

Опубликована: Янв. 2, 2025

This review examines the giant elastic protein titin and its critical roles in heart function, both health disease, as discovered since identification nearly 50 years ago. Encoded by TTN (titin gene), has emerged a major disease locus for cardiac disorders. Functionally, acts third myofilament type, connecting sarcomeric Z-disks M-bands, regulating myocardial passive stiffness stretch sensing. Its I-band segment, which includes N2B element PEVK (proline, glutamate, valine, lysine-rich regions), serves viscoelastic spring, adjusting sarcomere length force response to stretch. The details how alternative splicing of pre-mRNA produces different isoforms that greatly impact tension under physiological pathological conditions. Key posttranslational modifications, especially phosphorylation, play crucial titin’s stiffness, allowing rapid adaptation changing hemodynamic demands. Abnormal modifications dysregulation are linked diseases such failure with preserved ejection fraction, where increased impairs diastolic function. In addition, discusses importance A-band region setting thick filament enhancing Ca² + sensitivity, contributing Frank-Starling Mechanism heart. truncating variants frequently associated dilated cardiomyopathy, outlines potential mechanisms, including haploinsufficiency, disarray, altered regulation. Variants have also been conditions peripartum cardiomyopathy chemotherapy-induced cardiomyopathy. Therapeutic avenues explored, targeting factors RBM20 (RNA binding motif 20) adjust isoform ratios or using engineered tissues study mechanisms. Advances genetic engineering, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats), offer promise modifying treat titin-related cardiomyopathies. comprehensive highlights structural, mechanical, signaling function mutations on diseases.

Язык: Английский

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The Role of SGLT2-Inhibitors Across All Stages of Heart Failure and Mechanisms of Early Clinical Benefit: From Prevention to Advanced Heart Failure

Biomedicines, Год журнала: 2025, Номер 13(3), С. 608 - 608

Опубликована: Март 3, 2025

Sodium-glucose cotransporter-2 inhibitors (SGLT2i), initially developed as antihyperglycemic agents, have revolutionized heart failure (HF) management, offering substantial benefits across all stages and phenotypes of the disease. Regardless left ventricular ejection fraction (LVEF), these agents proven efficacy in both chronic acute HF presentations. This review explores SGLT2i applications spanning continuum, from early (Stage A) at-risk individuals to mitigation progression advanced D). Evidence numerous trials has shown that significantly lower rates hospitalization, improve renal function, decreases cardiovascular mortality, highlighting their multifaced mechanisms action care. also highlights potential by which exert beneficial effects on systems, each contributing sustained clinical improvements. However, integration into guideline-directed medical therapy poses practical challenges, including initiation timing, dosing, monitoring, are addressed support effective treatment adaptation patient populations. Ultimately, this provides a comprehensive assessment foundational HF, emphasizing role an intervention multiple aimed at improving outcomes entire spectrum.

Язык: Английский

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BNP and NT-proBNP as prognostic biomarkers for the prediction of adverse outcomes in HFpEF patients: A systematic review and meta-analysis

Heart Failure Reviews, Год журнала: 2024, Номер unknown

Опубликована: Окт. 7, 2024

Язык: Английский

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Assessing the risk of heart failure in type 2 diabetes: a prediction algorithm to sustain the evaluation of NT-proBNP in primary care

Endocrine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 12, 2025

Язык: Английский

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Evolution of the Quality of Care in Patients with Decompensated Heart Failure in a Venezuelan Hospital

Journal of Clinical Medicine, Год журнала: 2025, Номер 14(2), С. 644 - 644

Опубликована: Янв. 20, 2025

Background/Objectives: Several parameters have been proposed for the objective measurement of quality care (QoC) and breaches in patients with heart failure (HF). Therefore, this study was to evaluate measures QoC inpatients decompensated HF cardiology department a tertiary Venezuelan hospital. Methods: An observational, descriptive, ambispective conducted adults all genders diagnosed between 2022 2024. Sociodemographic, clinical, therapeutic variables were assessed, as well psychobiologic habits, QoC, readmissions, in-hospital mortality within first 6 months care. Results: Among 131 subjects evaluated, average age 63.6 ± 14.1 years, 58% (n = 76) being male. most common programming follow-up consultations (98.5%; n 129), followed by prescription beta-blockers (90.1%; 118). upwards trend also observed later years regarding frequency left ventricle ejection fraction (LVEF) assessment (p < 0.001), use iSGLT2 0.03). During follow-up, 36.6% died months, those NYHA class IV showing higher probability death (OR: 3.84; CI95%: 0.89–16.55; 0.04). Conclusions: The population similar previous reports, LVEF particularly significant increase recent years.

Язык: Английский

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Update on the Efficacy and Safety of Sodium–Glucose Co-Transporter 2 Inhibitors in Patients with Chronic Diseases: A Systematic Review and Meta-Analysis

Medicina, Год журнала: 2025, Номер 61(2), С. 202 - 202

Опубликована: Янв. 23, 2025

Background: Sodium–glucose co-transporter-2 (SGLT2) inhibitors have emerged as vital medications for the management of type 2 diabetes mellitus (T2DM). Numerous studies highlighted cardioprotective and renal protective benefits SGLT2 inhibitors. Consequently, it is essential to assess their efficacy safety in patients with chronic diseases. Method: We conducted a systematic review meta-analysis randomized controlled trials (RCTs) evaluating effects on major cardiovascular outcomes T2DM, heart failure (HF), kidney disease (CKD). searched PubMed, Cochrane, Embase databases published between 30 September 2021 17 May 2023. The primary interest included nonfatal myocardial infarction (MI), hospitalization (HHF), death, stroke. assessed were hypoglycemia, urinary tract infections (UTIs), acute injury (AKI). Result: identified 13 RCTs involving 90,413 participants. In significantly reduced risk MI by 12% (hazard ratio [HR] = 0.88, 95% confidence interval [CI]: 0.78–0.98), HHF 33% (HR 0.67, CI: 0.62–0.74), cardiac death 15% 0.95, 0.80–1.13). However, they did not reduce stroke 0.85, 0.75–0.95). HF, 28% 0.72, 0.66–0.77) 0.80–0.96). For CKD, 35% 0.65, 0.55–0.76) 16% 0.84, 0.73–0.96). Regarding outcomes, increase hypoglycemia or nor (UTIs) HF (AKI) HF. UTIs 8% (risk [RR] 1.08, 1.01–1.16) T2DM AKI 22% (RR 0.78, 0.67–0.89) 19% 0.81, 0.69–0.97) respectively. Conclusions: demonstrated significant improvement CKD while also maintaining favorable profile. These findings advocate broader application diseases, particularly reducing incidence MI, HHF, death. Further research optimize use across diverse patient populations stages disease.

Язык: Английский

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Acute Heart Failure and Non-Ischemic Cardiomyopathies: A Comprehensive Review and Critical Appraisal

Diagnostics, Год журнала: 2025, Номер 15(5), С. 540 - 540

Опубликована: Фев. 23, 2025

Acute heart failure (AHF) is a complex clinical syndrome characterized by the rapid or gradual onset of symptoms and/or signs (HF), leading to an unplanned hospital admission emergency department visit. AHF cause hospitalization in patients over 65 years, thus significantly impacting public health care. However, its prognosis remains poor with high rates mortality and rehospitalization. Many pre-existing cardiac conditions can lead AHF, but it also arise de novo due acute events. Therefore, understanding etiology could improve patient management outcomes. Cardiomyopathies (CMPs) are heterogeneous group muscle diseases, including dilated cardiomyopathy (DCM), hypertrophic (HCM), restrictive (RCM), non-dilated (NDLVC), arrhythmogenic right ventricular (ARVC), that frequently present HF. Patients CMPs under-represented studies compared other etiologies, therefore therapeutic responses prognoses remain unknown. In DCM, represents most frequent death despite treatment improvements. Additionally, DCM first indication for transplant (HT) among young middle-aged adults. HCM, progression rare more concomitant severe left ventricle (LV) obstruction hypertrophy LV systolic dysfunction. HF natural evolution RCM associated outcomes irrespective etiology. Furthermore, while occurrence ARVC, this condition NDLVC currently manuscript, we assessed available evidence on CMPs. Data presentation, management, according specific limited. Future assessing treatment, warranted.

Язык: Английский

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Sodium-glucose co-transporter 2 inhibitors: a pleiotropic drug in humans with promising results in cats

Frontiers in Veterinary Science, Год журнала: 2025, Номер 12

Опубликована: Фев. 28, 2025

Diabetes mellitus is a common metabolic disease in humans and cats. Cats share several features of human type-2 diabetes can be considered an animal model for this disease. In the last decade, sodium-glucose transporter 2 inhibitors (SGLT2i) have been used successfully as class hypoglycemic drug that inhibits reabsorption glucose from renal proximal tubules, consequently managing hyperglycemia through glycosuria. Furthermore, SGLT2i shown to cardiac, renal, other protective effects diabetic acting pleiotropic drug. Currently, at least six are approved by Food Drug Administration (FDA) use with diabetes, recently, two drugs were This narrative review focuses on treat We summarize data support controlling protecting against cardiovascular damage. also available literature regarding benefits these well Adverse related discussed.

Язык: Английский

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Prognostic Impact of HFpEF in Hypertrophic Cardiomyopathy: A Machine Learning-Based Risk Stratification Study

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

Background: Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder that often progresses to heart failure with preserved ejection fraction (HFpEF), substantially impacting patient prognosis. However, the clinical characteristics and prognostic significance of HFpEF in HCM are not well understood. This study aims identify key predictors adverse outcomes patients develop machine learning-based risk stratification model for improved management. Methods: retrospective cohort analyzed data from 2,615 who were evaluated at four tertiary medical centers between October 1, 2009, December 31, 2024. Of these, 1,152 diagnosed based on American Heart Association (AHA) criteria. Clinical characteristics, echocardiographic parameters, laboratory biomarkers assessed, all-cause mortality transplantation as primary endpoints. Cox proportional hazards regression models employed independent factors. Additionally, learning algorithms, including XGBoost, used predictive model. Results: HFpEF had significantly greater left ventricular septal thickness (19.01 ± 5.86 mm vs. 16.62 5.65 mm, p < 0.001), higher preoperative LVOT gradients (52.97 41.35 mmHg 40.72 38.08 mmHg, elevated BNP levels (2,281.63 1,761.16 pg/mL 365.46 193.07 pg/mL, 0.001). Both univariate multivariate analysis identified (HR: 1.028, 95% CI: 1.018–1.038, 0.001) atrial fibrillation 4.028, 1.929–8.411, cardiovascular events. The XGBoost-based outperformed traditional methods, achieving an area under receiver operating characteristic curve (AUC) 0.90, accuracy 85.4%, sensitivity 83.9%, specificity 86.8%. Conclusions: worsens prognosis patients, emphasizing importance early identification stratification. mortality. demonstrated superior performance compared conventional presenting promising AI-driven approach personalized assessment. Future studies should focus prospective validation, novel HFpEF-targeted therapeutics, integration AI decision-making.

Язык: Английский

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Transition to Advanced Heart Failure: From Identification to Improving Prognosis

Journal of Cardiovascular Development and Disease, Год журнала: 2025, Номер 12(3), С. 104 - 104

Опубликована: Март 17, 2025

Advanced heart failure (AHF) represents the terminal stage of (HF), characterized by persistent symptoms and functional limitations despite optimal guideline-directed medical therapy (GDMT). This review explores clinical definition, pathophysiology, therapeutic approaches for AHF. Characterized severe symptoms, New York Heart Association (NYHA) class III-IV, significant cardiac dysfunction, frequent hospitalizations, AHF presents substantial challenges in prognosis management. Pathophysiological mechanisms include neurohormonal activation, ventricular remodeling, systemic inflammation, leading to reduced output organ dysfunction. Therapeutic strategies involve a multidisciplinary approach, including pharmacological treatments, device-based interventions like assisted devices, advanced options such as transplantation. Despite progress, management faces limitations, disparities access care need personalized approaches. Novel therapies, artificial intelligence, remote monitoring technologies offer future opportunities improve outcomes. Palliative care, which focuses on symptom relief quality life, remains crucial patients ineligible invasive interventions. Early identification timely intervention are pivotal enhancing survival outcomes this vulnerable population. underscores necessity integrating innovative technologies, medicine, robust palliative into address its high morbidity mortality.

Язык: Английский

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