Ambrosino Pasquale, Parrella Paolo, Formisano Roberto, Perrotta Giovanni, D'Anna Silvestro Ennio, Mosella Marco, Papa Antimo, Maniscalco Mauro
Istituti Clinici Scientifici Maugeri IRCCS, Cardiac Rehabilitation Unit of Telese Terme Institute, 82037 Telese Terme, Italy.
Ospedale Sacro Cuore di Gesù Fatebenefratelli, 82100 Benevento, Italy.
J Clin Med. 2022 Mar 7;11(5):1452. doi: 10.3390/jcm11051452.
Endothelial dysfunction has been proposed as the common pathogenic background of most manifestations of coronavirus disease 2019 (COVID-19). Among these, some authors also reported an impaired exercise response during cardiopulmonary exercise testing (CPET). We aimed to explore the potential association between endothelial dysfunction and the reduced CPET performance in COVID-19 survivors.
36 consecutive COVID-19 survivors underwent symptom-limited incremental CPET and assessment of endothelium-dependent flow-mediate dilation (FMD) according to standardized protocols.
A significantly higher FMD was documented in patients with a preserved, as compared to those with a reduced, exercise capacity (4.11% ± 2.08 vs. 2.54% ± 1.85, = 0.048), confirmed in a multivariate analysis (β = 0.899, = 0.038). In the overall study population, FMD values showed a significant Pearson's correlation with two primary CPET parameters, namely ventilation/carbon dioxide production (VE/VCO) slope (r = -0.371, = 0.026) and end-tidal carbon dioxide tension (PCO) at peak (r = 0.439, = 0.007). In multiple linear regressions, FMD was the only independent predictor of VE/VCO slope (β = -1.308, = 0.029) and peak PCO values (β = 0.779, = 0.021). Accordingly, when stratifying our study population based on their ventilatory efficiency, patients with a ventilatory class III-IV (VE/VCO slope ≥ 36) exhibited significantly lower FMD values as compared to those with a ventilatory class I-II.
The alteration of endothelial barrier properties in systemic and pulmonary circulation may represent a key pathogenic mechanism of the reduced CPET performance in COVID-19 survivors. Personalized pharmacological and rehabilitation strategies targeting endothelial function may represent an attractive therapeutic option.
内皮功能障碍被认为是2019冠状病毒病(COVID-19)大多数表现的共同致病背景。其中,一些作者还报告了心肺运动试验(CPET)期间运动反应受损。我们旨在探讨COVID-19幸存者内皮功能障碍与CPET表现降低之间的潜在关联。
36例连续的COVID-19幸存者按照标准化方案进行症状限制递增CPET,并评估内皮依赖性血流介导的血管舒张(FMD)。
与运动能力降低的患者相比,运动能力保留的患者记录到显著更高的FMD(4.11%±2.08对2.54%±1.85,P = 0.048),多变量分析证实(β = 0.899,P = 0.038)。在整个研究人群中,FMD值与两个主要CPET参数显著相关,即通气/二氧化碳产生(VE/VCO₂)斜率(r = -0.371,P = 0.026)和峰值时的呼气末二氧化碳分压(PCO₂)(r = 0.439,P = 0.007)。在多元线性回归中,FMD是VE/VCO₂斜率(β = -1.308,P = 0.029)和峰值PCO₂值(β = 0.779,P = 0.021)的唯一独立预测因子。因此,根据通气效率对研究人群进行分层时,通气分级为III-IV级(VE/VCO₂斜率≥36)的患者与通气分级为I-II级的患者相比,FMD值显著更低。
全身和肺循环中内皮屏障特性的改变可能是COVID-19幸存者CPET表现降低的关键致病机制。针对内皮功能的个性化药物和康复策略可能是一种有吸引力的治疗选择。