Rajah Megan R, Marais Erna, Maarman Gerald J, Doubell Emma, Doubell Anton F, Herbst Philip G
Division of Cardiology, Department of Medicine, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Cape Town 8000, South Africa.
Centre for Cardio-Metabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town 8000, South Africa.
Diagnostics (Basel). 2025 Apr 30;15(9):1143. doi: 10.3390/diagnostics15091143.
Myocardial fibrosis in aortic stenosis (AS) is associated with a significant risk of poor clinical outcomes. Myocardial fibrosis can be evaluated using cardiovascular magnetic resonance (CMR) imaging and may be useful for risk-stratifying patients at high risk for poorer outcomes. A circulating biomarker of fibrosis may be a cheaper, more accessible alternative to CMR in lower-to-middle-income countries. This study evaluated the correlation between serum biomarkers of myocardial fibrosis (TGF-β1, PICP, and PIIINP) with CMR markers of myocardial fibrosis (T1 mapping, extracellular volume fraction (ECV), and late gadolinium enhancement (LGE)). Twenty-one high-gradient (mean gradient ≥ 40 mmHg) severe AS (aortic valve area < 1.0 cm) participants underwent T1 mapping and LGE imaging using CMR. Blood serum was collected for enzyme-linked immunosorbent assays of the listed biomarkers. Serum TGF-β1 was associated significantly with the global T1 relaxation time on CMR (r = 0.46 with 95% CI 0.03 to 0.74, = 0.04). In the high T1 time group (1056 vs. 1023 ms), trends toward elevated serum TGF-β1 concentration (13,044 vs. 10,341 pg/mL, = 0.08) and ECV (26% vs. 24%, = 0.07) were observed. The high T1 and trend towards elevated TGF-β1 concentration in this group tracked adverse LV remodeling and systolic dysfunction. There were no significant associations between PICP/PIIINP and T1 mapping or between the biomarkers and LGE quantity. Serum TGF-β1 is a potential surrogate for diffuse interstitial fibrosis measured by T1 mapping and ECV on CMR. Serum PICP and PIIINP may be less appropriate as surrogate markers of fibrosis in view of their temporal trends over the course of AS. Larger studies are needed to validate the utility of TGF-β1 as a marker of diffuse fibrosis and to evaluate the utility of serial PICP/PIIINP measurements to predict decompensation.
主动脉瓣狭窄（AS）中的心肌纤维化与临床预后不良的显著风险相关。心肌纤维化可通过心血管磁共振（CMR）成像进行评估，且可能有助于对预后较差的高危患者进行风险分层。在中低收入国家，纤维化的循环生物标志物可能是比CMR更便宜、更易获取的替代方法。本研究评估了心肌纤维化的血清生物标志物（转化生长因子-β1、I型前胶原羧基端前肽（PICP）和III型前胶原氨基端前肽（PIIINP））与心肌纤维化的CMR标志物（T1 mapping、细胞外容积分数（ECV）和延迟钆增强（LGE））之间的相关性。21名高梯度（平均梯度≥40 mmHg）重度AS（主动脉瓣面积<1.0 cm²）参与者接受了CMR的T1 mapping和LGE成像检查。采集血清用于所列生物标志物的酶联免疫吸附测定。血清转化生长因子-β1与CMR上的整体T1弛豫时间显著相关（r = 0.46，95%可信区间为0.03至0.74，P = 0.04）。在高T1时间组（1056对1023 ms）中，观察到血清转化生长因子-β1浓度升高的趋势（13,044对10,341 pg/mL，P = 0.08）和ECV升高的趋势（26%对24%，P = 0.07）。该组中高T1及转化生长因子-β1浓度升高的趋势与不良的左心室重构和收缩功能障碍相关。PICP/PIIINP与T1 mapping之间或生物标志物与LGE量之间均无显著关联。血清转化生长因子-β1是通过CMR上的T1 mapping和ECV测量的弥漫性间质纤维化的潜在替代指标。鉴于血清PICP和PIIINP在AS病程中的时间趋势，它们作为纤维化替代标志物可能不太合适。需要开展更大规模的研究来验证转化生长因子-β1作为弥漫性纤维化标志物的效用，并评估连续测量PICP/PIIINP以预测失代偿的效用。
