Clonal Hematopoiesis Is Associated With Long-Term Adverse Outcomes Following Cardiac Surgery.

BACKGROUND: Cardiac surgery triggers sterile innate immune responses leading to postoperative complications. Clonal hematopoiesis (CH) is associated with short-term inflammation-mediated outcomes after cardiac surgery. The impact of CH on long-term postoperative outcomes remains unknown. METHODS AND RESULTS: In this cohort study, patients undergoing elective cardiac surgery were included from January 2017 to September 2019. Patients were screened for CH using a predefined gene panel of 19 genes. Recorded clinical events were all-cause death, major adverse cardiac and cerebral events including cardiovascular death, myocardial infarction or nonscheduled coronary revascularization, stroke, and hospitalization for acute heart failure. The primary study outcome was time to a composite criterion including all-cause mortality and major adverse cardiac and cerebral events. Among 314 genotyped patients (median age: 67 years; interquartile range 59-74 years), 139 (44%) presented with CH, based on a variant allelic frequency ≥1%. Carriers of CH had a higher proportion of patients with a history of atrial fibrillation (26% for CH versus 17% for non-CH carriers, P=0.022). The most frequently mutated genes were DNMT3A, TET2, and ASXL1. After a median follow-up of 1203 [813-1435] days, the primary outcome occurred in 50 patients. After multivariable adjustment, CH was independently associated with a higher risk for the primary outcome (hazard ratio, 1.88 [95% CI, 1.05-3.41], P=0.035). Most adverse events occurred in patients carrying TET2 variants. CONCLUSIONS: In patients undergoing cardiac surgery, CH is frequent and associated with a 2-fold increased long-term risk for major adverse clinical outcomes. CH is a novel risk factor for long-term postcardiac surgery complications and might be useful to personalize management decisions. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03376165.

Feasibility and prognostic significance of ventricular-arterial coupling after myocardial infarction: the RIGID-MI cohort.

AIMS: The clinical significance and feasibility of the recently described non-invasive parameters exploring ventricular-arterial coupling (VAC) remain uncertain. This study aimed to assess VAC parameters for prognostic stratification in stable patients with left ventricular ejection fraction (LVEF) ≥40% following myocardial infarction (MI). METHODS AND RESULTS: Between 2018 and 2021, patients with LVEF ≥40% were evaluated 1 month following MI using transthoracic echocardiography (TTE) and arterial tonometry at rest and after a handgrip test. VAC was studied via the ratio between arterial elastance (Ea) and end-systolic LV elastance (Ees) and between pulse wave velocity (PWV) and global longitudinal strain (GLS). Patients were followed for major adverse cardiovascular events (MACE): all-cause death, acute heart failure, stroke, AMI, and urgent cardiovascular hospitalization. Among the 374 patients included, Ea/Ees and PWV/GLS were obtained at rest for 354 (95%) and 253 patients (68%), respectively. Isometric exercise was workable in 335 patients (85%). During a median follow-up of 32 months (interquartile range: 16-42), 41 (11%) MACE occurred. Patients presenting MACE were significantly older and had a higher prevalence of peripheral arterial disease, lower GLS, higher Ea, PWV, and PWV/GLS ratio. The Ea/Ees ratio and standard TTE parameters during isometric exercise were not associated with MACE. After adjustment, the PWV/GLS ratio was the only VAC parameter independently associated with outcome. Receiver operating characteristic curve analysis identified a PWV/GLS ratio >0.70 (Youden's index = 0.37) as the best threshold to identify patients developing MACE: hazard ratio (95% confidence interval) = 2.2 (1.14-4.27), P = 0.02. CONCLUSION: The PWV/GLS ratio, assessed 1 month after MI, identifies a group of patients at higher risk of MACE providing additional value on top of conventional non-invasive parameters.

Hematopoietic Somatic Mosaicism Is Associated With an Increased Risk of Postoperative Atrial Fibrillation.

BACKGROUND: On-pump cardiac surgery triggers sterile inflammation and postoperative complications such as postoperative atrial fibrillation (POAF). Hematopoietic somatic mosaicism (HSM) is a recently identified risk factor for cardiovascular diseases and results in a shift toward a chronic proinflammatory monocyte transcriptome and phenotype. OBJECTIVES: The aim of this study was to assess the prevalence, characteristics, and impact of HSM on preoperative blood and myocardial myeloid cells as well as on outcomes after cardiac surgery. METHODS: Blood DNA from 104 patients referred for surgical aortic valve replacement (AVR) was genotyped using the HemePACT panel (576 genes). Four screening methods were applied to assess HSM, and postoperative outcomes were explored. In-depth blood and myocardial leukocyte phenotyping was performed in selected patients using mass cytometry and preoperative and postoperative RNA sequencing analysis of classical monocytes. RESULTS: The prevalence of HSM in the patient cohort ranged from 29%, when considering the conventional HSM panel (97 genes) with variant allelic frequencies ≥2%, to 60% when considering the full HemePACT panel and variant allelic frequencies ≥1%. Three of 4 explored HSM definitions were significantly associated with higher risk for POAF. On the basis of the most inclusive definition, HSM carriers exhibited a 3.5-fold higher risk for POAF (age-adjusted OR: 3.5; 95% CI: 1.52-8.03; P = 0.003) and an exaggerated inflammatory response following AVR. HSM carriers presented higher levels of activated CD64+CD14+CD16- circulating monocytes and inflammatory monocyte-derived macrophages in presurgery myocardium. CONCLUSIONS: HSM is frequent in candidates for AVR, is associated with an enrichment of proinflammatory cardiac monocyte-derived macrophages, and predisposes to a higher incidence of POAF. HSM assessment may be useful in the personalized management of patients in the perioperative period. (Post-Operative Myocardial Incident & Atrial Fibrillation [POMI-AF]; NCT03376165).