Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15. Col. Belisario Dominguez Sección XVI, Tlalpan, Mexico City 14080, Mexico.
Radiology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico.
Semin Arthritis Rheum. 2019 Oct;49(2):273-278. doi: 10.1016/j.semarthrit.2019.02.005. Epub 2019 Feb 11.
In previous studies we showed that prevalence of myocardial fibrosis as assessed by late enhancement on cardiac MRI in SSc patients is 45% and is associated to diffuse disease (dcSSc) and lower left ventricle ejection fraction; microvascular damage defined as decreased perfusion on cardiac MRI after adenosine infusion, was also very frequent (79%). Our aim was to identify baseline characteristics associated to the development of cardiovascular outcomes (heart failure, coronary artery disease, arrhythmias, vasculopathy, elevated systolic pulmonary artery pressure and death) in SSc patients with previously documented myocardial fibrosis and microvascular damage.
We included 62 SSc patients who participated in the study of prevalence of myocardial fibrosis (2008-2010) and in our local SSc cohort. We performed baseline clinical evaluation, cardiac MRI, coronary CT angiography, transthoracic echocardiogram, and yearly clinical and cardiovascular evaluation that included Medsger's severity scale items, electrocardiogram, echocardiogram, chest X-ray or HRCT and spirometry; we registered presence and severity of internal organ involvement and cardiovascular outcomes. Ordinal variables were analyzed using Chi square test and Fisher test when appropriate, numeric variables were compared using Student's t-test or Mann Whitney U when appropriate, logistic regression and Cox proportional hazard ratio were used to perform multivariable analysis.
We obtained follow-up information from 62 patients (29 dcSSc, 33 lcSSc), mean follow-up was 43.5 months. Multivariable analysis showed that elevated basal ultrasensitive CRP was associated to mortality (p = 0.004, OR: 11.9, 95% CI 2.1-65.7) and recurrent digital tip ischemic ulcers (p = 0.001, OR 26.8, 95% CI 3,9-181.3) on follow-up. Myocardial fibrosis, particularly in the middle segments (p = 0.01, OR: 11.49, 95% CI 1.6-83), and older age (p = 0.02, OR: 1.11, 95% CI 1.01-1.22) were associated to heart failure on follow-up. Higher maximum mRSS was associated to coronary artery disease (p = 0.02, OR: 1.2, 95% CI 1.02-1.38), while insertion point fibrosis (p = 0.001, OR: 12.5 95% CI 2.7-56.6) was associated to recurrent digital tip ischemic ulcers.
This study shows that myocardial fibrosis, elevated ultrasensitive CRP, and higher maximum mRSS are independent predictors of cardiovascular outcomes in SSc patients. Future studies should focus on early preventive and therapeutic strategies for this group of patients.
在之前的研究中,我们发现通过心脏 MRI 上的晚期钆增强评估,系统性硬化症(SSc)患者的心肌纤维化患病率为 45%,且与弥漫性疾病(dcSSc)和较低的左心室射血分数相关;通过腺苷输注后心脏 MRI 评估的微血管损伤(定义为灌注减少)也非常常见(79%)。我们的目的是确定基线特征与先前有心肌纤维化和微血管损伤记录的 SSc 患者心血管结局(心力衰竭、冠状动脉疾病、心律失常、血管病变、肺动脉收缩压升高和死亡)的发展相关。
我们纳入了 62 名参加心肌纤维化患病率研究(2008-2010 年)的 SSc 患者,以及我们当地的 SSc 队列。我们进行了基线临床评估、心脏 MRI、冠状动脉 CT 血管造影、经胸超声心动图和每年的临床和心血管评估,包括 Medsger 严重程度量表项目、心电图、超声心动图、胸部 X 线或 HRCT 和肺功能检查;我们记录了内部器官受累和心血管结局的存在和严重程度。对于有序变量,使用卡方检验和 Fisher 检验进行分析(如果适用),对于数值变量,使用学生 t 检验或 Mann Whitney U 检验进行比较(如果适用),使用逻辑回归和 Cox 比例风险比进行多变量分析。
我们从 62 名患者(29 名 dcSSc,33 名 lcSSc)获得了随访信息,平均随访时间为 43.5 个月。多变量分析显示,基础超敏 C 反应蛋白升高与死亡率(p=0.004,OR:11.9,95%CI 2.1-65.7)和随访时复发性指尖缺血性溃疡(p=0.001,OR:26.8,95%CI 3.9-181.3)相关。心肌纤维化,特别是中段(p=0.01,OR:11.49,95%CI 1.6-83)和年龄较大(p=0.02,OR:1.11,95%CI 1.01-1.22)与随访时的心力衰竭相关。最大 mRSS 较高与冠状动脉疾病相关(p=0.02,OR:1.2,95%CI 1.02-1.38),而插入点纤维化(p=0.001,OR:12.5,95%CI 2.7-56.6)与复发性指尖缺血性溃疡相关。
本研究表明,心肌纤维化、超敏 C 反应蛋白升高和最大 mRSS 是 SSc 患者心血管结局的独立预测因素。未来的研究应关注这组患者的早期预防和治疗策略。