Fabiani Iacopo, Santoni Tatiana, Angelillis Marco, Petricciuolo Serena, Colli Andrea, Pellegrini Giovanni, Mazzei Deborah, Pugliese Nicola Riccardo, Petronio Anna Sonia, De Caterina Raffaele
Cardiac, Thoracic and Vascular Department, Pisa University Hospital and University of Pisa, Via Paradisa 2, 56124 Pisa, Italy.
Department of Surgical, Medical, Molecular Pathology and Critical Area, Pisa University Hospital and University of Pisa, Via Paradisa 2, 56124 Pisa, Italy.
J Clin Med. 2020 Sep 17;9(9):2998. doi: 10.3390/jcm9092998.
Frailty is an important outcome predictor in patients with aortic stenosis who are candidates for transcatheter or surgical aortic valve replacement (AVR). Growth/differentiation factor 15 (GDF15) is a cytokine playing a role in the pathophysiology of ventricular remodeling. We assessed its potential role as an independent soluble biomarker of frailty in these patients. We studied 62 patients (age, mean 79 years, 95% confidence interval (CI) 77-81; 54.8% female) with severe aortic valve stenosis and candidates for AVR. We systematically assessed pre-intervention GDF15 levels for their relationship with frailty (Katz score) and echocardiographic parameters of left ventricular dysfunction/remodeling. Fifteen hypertensive patients with left ventricular (LV) hypertrophy served as controls. Patients with aortic valve stenosis featured higher GDF15 levels than controls (1773, 95% CI 1574-1971 pg/mL vs. 775, 95% CI 600-950 pg/mL, respectively, < 0.0001). Subjects in the upper GDF15 tertile were older ( = 0.004), with a more advanced NYHA functional class ( = 0.04) and a higher prevalence of impaired renal function ( = 0.004). Such patients also showed a higher frailty score ( = 0.04) and higher indices of LV dysfunction, including reduced global longitudinal strain ( = 0.01) and a higher left ventricular mass ( = 0.001). GDF15 was significantly related to the Katz score, and predicted (OR 1.05; 95% CI 0.9-1.1; = 0.03) a low (<5) Katz score, independent of the relationship with LV mass, age, renal function or indices of LV dysfunction. GDF15 is increased in patients with severe aortic stenosis and appears to be a soluble correlate of patients' frailty, independent of indices of left ventricular dysfunction.
衰弱是主动脉瓣狭窄患者经导管或外科主动脉瓣置换术（AVR）候选者的重要预后预测指标。生长/分化因子15（GDF15）是一种在心室重塑病理生理学中起作用的细胞因子。我们评估了其作为这些患者衰弱独立可溶性生物标志物的潜在作用。我们研究了62例重度主动脉瓣狭窄且为AVR候选者的患者（年龄，平均79岁，95%置信区间（CI）77 - 81；54.8%为女性）。我们系统评估了干预前GDF15水平与衰弱（Katz评分）以及左心室功能障碍/重塑的超声心动图参数之间的关系。15例左心室（LV）肥厚的高血压患者作为对照。主动脉瓣狭窄患者的GDF15水平高于对照组（分别为1773，95%CI 1574 - 1971 pg/mL与775，95%CI 600 - 950 pg/mL，<0.0001）。GDF15三分位数较高的受试者年龄较大（=0.004），纽约心脏协会（NYHA）功能分级更高级（=0.04），肾功能受损的患病率更高（=0.004）。这些患者还表现出更高的衰弱评分（=0.04）和更高的左心室功能障碍指标，包括整体纵向应变降低（=0.01）和左心室质量增加（=0.001）。GDF15与Katz评分显著相关，并预测（OR 1.05；95%CI 0.9 - 1.1；=0.03）低（<5）Katz评分，独立于与左心室质量、年龄、肾功能或左心室功能障碍指标的关系。严重主动脉瓣狭窄患者的GDF1增加，似乎是患者衰弱的可溶性相关因素，独立于左心室功能障碍指标。
