From the Department of Medicine, Cardiovascular Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass (A. Schulz); Department of Cardiology and Pneumology, University Medical Center Göttingen, Georg-August-University Göttingen, Robert-Koch-Str. 40, 37099 Göttingen, Germany (A. Schulz, I.N.S., S.J.B., T.L., R.E., G.H., U.R., A. Schuster); German Center for Cardiovascular Research (DZHK), Partner Site Lower Saxony, Germany (A. Schulz, I.N.S., S.J.B., T.L., R.E., G.H., U.R., A. Schuster); School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom (S.J.B., A. Schuster); Institute of Biomedical Imaging, University of Graz, Graz, Austria (A.S.A.); FORUM Radiology, Rosdorf, Germany (J.T.K.); German Center for Cardiovascular Research (DZHK), Partner Site Lower Saxony, Germany (J.T.K.); Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital Würzburg, Würzburg, Germany (A.H.); Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany (C.M.); Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, Calif (P.S.T.); VA Palo Alto Health Care System, Palo Alto, Calif (P.S.T.); and FORUM Cardiology, Rosdorf, Germany (A. Schuster).
Radiol Cardiothorac Imaging. 2024 Aug;6(4):e230344. doi: 10.1148/ryct.230344.
Purpose To investigate if aortic stiffening as detected with cardiac MRI is an early phenomenon in the development and progression of heart failure with preserved ejection fraction (HFpEF). Materials and Methods Both clinical and preclinical studies were performed. The clinical study was a secondary analysis of the prospective HFpEF stress trial (August 2017 through September 2019) and included 48 participants (median age, 69 years [range, 65-73 years]; 33 female, 15 male) with noncardiac dyspnea (NCD, = 21), overt HFpEF at rest (pulmonary capillary wedge pressure [PCWP] ≥ 15 mm Hg, = 14), and masked HFpEF at rest diagnosed during exercise stress (PCWP ≥ 25 mm Hg, = 13) according to right heart catheterization. Additionally, all participants underwent echocardiography and cardiac MRI at rest and during exercise stress. Aortic pulse wave velocity (PWV) was calculated. The mechanistic preclinical study characterized cardiac function and structure in transgenic mice with induced arterial stiffness (Runx2-smTg mice). Statistical analyses comprised nonparametric and parametric comparisons, Spearman correlations, and logistic regression models. Results Participants with HFpEF showed increased PWV (NCD vs masked HFpEF: 7.0 m/sec [IQR: 5.0-9.5 m/sec] vs 10.0 m/sec [IQR: 8.0-13.4 m/sec], = .005; NCD vs overt HFpEF: 7.0 m/sec [IQR: 5.0-9.5 m/sec] vs 11.0 m/sec [IQR: 7.5-12.0 m/sec], = .01). Increased PWV correlated with higher PCWP ( = .006), left atrial and left ventricular long-axis strain (all < .02), and N-terminal pro-brain natriuretic peptide levels ( < .001). Participants with overt HFpEF had higher levels of myocardial fibrosis, as demonstrated by increased native T1 times (1199 msec [IQR: 1169-1228 msec] vs 1234 msec [IQR: 1208-1255 msec], = .009). Aortic stiffness was independently associated with HFpEF on multivariable analyses (odds ratio, 1.31; = .049). Runx2-smTG mice exhibited an "HFpEF" phenotype compared with wild-type controls, with preserved left ventricular fractional shortening but an early and late diastolic mitral annulus velocity less than 1 (mean, 0.67 ± 0.39 [standard error of the mean] vs 1.45 ± 0.47; = .004), increased myocardial collagen deposition (mean, 11% ± 1 vs 2% ± 1; < .001), and increased brain natriuretic peptide levels (mean, 171 pg/mL ± 23 vs 101 pg/mL ± 10; < .001). Conclusion This study provides translational evidence that increased arterial stiffness might be associated with development and progression of HFpEF and may facilitate its early detection. MR Functional Imaging, MR Imaging, Animal Studies, Cardiac, Aorta, Heart ClinicalTrials.gov identifier NCT03260621 © RSNA, 2024.
目的 探讨心脏 MRI 检测到的主动脉僵硬度是否是射血分数保留型心力衰竭（HFpEF）发生和进展的早期现象。
材料与方法 进行了临床和临床前研究。临床研究是前瞻性 HFpEF 应激试验（2017 年 8 月至 2019 年 9 月）的二次分析，纳入 48 名参与者（中位年龄 69 岁[范围，65-73 岁]；33 名女性，15 名男性），非心源性呼吸困难（NCD， = 21）、静息时显性 HFpEF（肺毛细血管楔压[PCWP]≥15mmHg， = 14）和静息时运动应激时诊断的隐匿性 HFpEF（PCWP≥25mmHg， = 13）根据右心导管检查。此外，所有参与者在静息和运动应激时均接受超声心动图和心脏 MRI 检查。计算主动脉脉搏波速度（PWV）。在诱导动脉僵硬的转基因小鼠中进行了机制性临床前研究，以确定心脏功能和结构。统计分析包括非参数和参数比较、Spearman 相关性和逻辑回归模型。
结果 HFpEF 患者的 PWV 增加（NCD 与隐匿性 HFpEF：7.0m/sec[IQR：5.0-9.5m/sec]与 10.0m/sec[IQR：8.0-13.4m/sec]， =.005；NCD 与显性 HFpEF：7.0m/sec[IQR：5.0-9.5m/sec]与 11.0m/sec[IQR：7.5-12.0m/sec]， =.01）。PWV 增加与更高的 PCWP 相关（ =.006）、左心房和左心室长轴应变（均 <.02）和 N 端脑利钠肽水平（ <.001）。显性 HFpEF 患者心肌纤维化水平较高，表现为心肌 T1 时间增加（1199ms[IQR：1169-1228ms]与 1234ms[IQR：1208-1255ms]， =.009）。多变量分析显示，主动脉僵硬与 HFpEF 独立相关（优势比，1.31； =.049）。Runx2-smTG 小鼠与野生型对照相比表现出“HFpEF”表型，保留左心室短轴缩短率，但早期和晚期舒张二尖瓣环速度小于 1（平均值，0.67±0.39[均数标准差]与 1.45±0.47； =.004），心肌胶原沉积增加（平均值，11%±1 与 2%±1； <.001），脑利钠肽水平升高（平均值，171pg/mL±23 与 101pg/mL±10； <.001）。
结论 本研究提供了转化证据，表明动脉僵硬度增加可能与 HFpEF 的发生和进展相关，并可能有助于其早期发现。
