RESUMEN
BACKGROUND: The role of cellular senescence in human heart failure (HF) remains unclear. The senescence-associated secretory phenotype (SASP) is composed of proteins released by senescent cells. We assessed the prognostic significance and biologic pathways associated with the SASP in human HF using a plasma proteomics approach. METHODS AND RESULTS: We measured 25 known SASP proteins among 2248 PHFS (Penn HF Study) participants using the SOMAScan V4 assay. We extracted the common variance in these proteins to generate SASP factor scores and assessed the relationship between these SASP factor scores and (1) all-cause death and (2) the composite of death or HF hospital admission. We also assessed the relationship of each SASP factor to 4746 other proteins, correcting for multiple comparisons, followed by pathway analyses. Two SASP factors were identified. Both factors were associated with older age, lower estimated glomerular filtration rate, and more advanced New York Heart Association class, among other clinical variables. Both SASP factors exhibited a significant positive association with the risk of death independent of the Meta-Analysis of Global-Group in Chronic HF score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. The 2 identified SASP factors were associated with 1201 and 1554 proteins, respectively, belonging to various pathways including the coagulation system, complement system, acute phase response signaling, and retinoid X receptor-related pathways that regulate cell metabolism. CONCLUSIONS: Increased SASP components are independently associated with adverse outcomes in HF. Biologic pathways associated with SASP are predominantly related to coagulation, inflammation, and cell metabolism.
Asunto(s)
Biomarcadores , Insuficiencia Cardíaca , Proteómica , Fenotipo Secretor Asociado a la Senescencia , Humanos , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/metabolismo , Masculino , Femenino , Biomarcadores/sangre , Pronóstico , Anciano , Persona de Mediana Edad , Proteómica/métodos , Senescencia Celular , Fragmentos de Péptidos , Péptido Natriurético EncefálicoRESUMEN
BACKGROUND: Kidney disease is common in heart failure with preserved ejection fraction (HFpEF). However, the biologic correlates and prognostic significance of kidney injury (KI), in HFpEF, beyond the estimated glomerular filtration rate (eGFR), are unclear. METHODS AND RESULTS: Using baseline plasma samples from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, we measured the following KI biomarkers: cystatin-C, fatty acid-binding protein-3, Beta-2 microglobulin, neutrophil gelatinase-associated lipocalin, and kidney-injury molecule-1. Factor analysis was used to extract the common variability underlying these biomarkers. We assessed the relationship between the KI-factor score and the risk of death or HF-related hospital admission in models adjusted for the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. We also assessed the relationship between the KI factor score and ~5000 plasma proteins, followed by pathway analysis. We validated our findings among HFpEF participants in the Penn Heart Failure Study. KI was associated with the risk of death or HF-related hospital admission independent of the Meta-Analysis Global Group in Chronic Heart Failure risk score and eGFR. Both the risk score and eGFR were no longer associated with death or HF-related hospital admission after adjusting for the KI factor score. KI was predominantly associated with proteins and biologic pathways related to complement activation, inflammation, fibrosis, and cholesterol homeostasis. KI was associated with 140 proteins, which reproduced across cohorts. Findings regarding biologic associations and the prognostic significance of KI were also reproduced in the validation cohort. CONCLUSIONS: KI is associated with adverse outcomes in HFpEF independent of baseline eGFR. Patients with HFpEF and KI exhibit a plasma proteomic signature indicative of complement activation, inflammation, fibrosis, and impaired cholesterol homeostasis.
Asunto(s)
Biomarcadores , Insuficiencia Cardíaca , Proteómica , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/mortalidad , Volumen Sistólico/fisiología , Masculino , Femenino , Anciano , Proteómica/métodos , Pronóstico , Biomarcadores/sangre , Persona de Mediana Edad , Tasa de Filtración Glomerular , Enfermedades Renales/sangre , Enfermedades Renales/fisiopatología , Enfermedades Renales/diagnóstico , Enfermedades Renales/mortalidad , Función Ventricular Izquierda , Antagonistas de Receptores de Mineralocorticoides/uso terapéutico , Riñón/fisiopatología , Factores de RiesgoRESUMEN
OBJECTIVE: Anterior and bileaflet degenerative mitral regurgitation repairs are challenging. We examined our early and late outcomes for repair using 4 techniques, without neochord repair. METHODS: Between February 1, 2006, and June 30, 2021, a total of 2368 patients received mitral valve ± other surgery by 1 surgeon, including 1160 with degenerative mitral regurgitation. Clinical follow-up was conducted annually (mean 6.8 ± 4.4 years). RESULTS: Repair was performed in 1137 patients (98%) (mean age, 60.5 ± 11.9 years). Repair rate varied between groups: 99% for isolated posterior leaflet (794/799), 91% for isolated anterior leaflet (83/91), and 96% for bileaflet prolapse (260/270; P < .001). Thirty-day mortality was 0.2%. On a scale of 0 to 4+ mitral regurgitation, mean mitral regurgitation grade decreased from 3.8 ± 0.6 preoperatively to 0.07 ± 0.3 at discharge, including moderate (2+) in 0.6% (7/1137) overall and 0.9% (3/343) with anterior prolapse. None were more than 2+ at discharge. Among the 3 groups of leaflet prolapse, there was no significant difference in long-term survival (P = .26), freedom from mitral valve reintervention (P = .12; 99.4% overall), and freedom from more than moderate (2+) mitral regurgitation (P = .16; 98.3% overall). The 4 most common anterior leaflet repair techniques (chord transfer 17%; commissuroplasty 10%; Alfieri [edge-to-edge] 6%); ring with posterior resection (4.3%) had similar freedom from 10-year reintervention (99.4%, 94%, 100%, and 100%, respectively; P = .29). CONCLUSIONS: Complex anterior leaflet prolapse repairs are successful using a variety of techniques without neochord implantation. Although neochords are popular, there are other ways to repair complex valves that do not require as much judgment and experience.
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INTRODUCTION: Esophageal thermal injury (ETI) is a well-recognized complication of atrial fibrillation (AF) ablation. Previous studies have demonstrated that direct esophageal cooling reduces ETI during radiofrequency AF ablation. The purpose of this study was to evaluate the use of an esophageal warming device to prevent ETI during cryoballoon ablation (CBA) for AF. METHODS: This prospective, double-blinded study enrolled 42 patients with symptomatic AF undergoing CBA. Patients were randomized to the treatment group with esophageal warming (42°C) using recirculated water through a multilumen, silicone tube inserted into the esophagus (EnsoETM®; Attune Medical) (WRM) or the control group with a luminal single-electrode esophageal temperature monitoring probe (LET). Patients underwent upper endoscopy esophagogastroduodenoscopy (EGD) the following day. ETI was classified into four grades. RESULTS: Baseline patient characteristics were similar between groups. Procedural characteristics including number of freezes, total freeze time, early freeze terminations, coldest balloon temperature, procedure duration, posterior wall ablation, and proton pump inhibitor and transesophageal echocardiogram use before procedure were not different between groups. The EGD was completed in 40/42 patients. There was significantly more ETI in the WRM group compared to the LET group (n = 8 [38%] vs. n = 1 [5%], p = 0.02). All ETI lesions were grade 1 (erythema) or 2 (superficial ulceration). Total freeze time in the left inferior pulmonary vein was predictive of ETI (360 vs. 300 s, p = 0.03). CONCLUSION: Use of a luminal heat exchange tube for esophageal warming during CBA for AF was paradoxically associated with a higher risk of ETI.