Letter by Nikolova et al Regarding Article, "Heart Failure With Preserved Ejection Fraction in Perspective".
Letter by Nikolova et al Regarding Article, "Heart Failure With Preserved Ejection Fraction in Perspective".
复制标题
Nikolova 等人关于文章“保留射血分数的心力衰竭”的信函。
DOI：
10.1161/circresaha.119.315583
复制
发表时间：
2019
影响因子：
20.1
通讯作者：
Shaw,RobinM
中科院分区：
文献类型：
--
作者：
Nikolova,AndrianaP;Hong,TingTing;Shaw,RobinM
我们要祝贺Pfeffer等人1对射血分数保留性心力衰竭（HFpEF）复杂综合征的当前知识状态的出色综述。作者提供了一个全面的历史和流行病学的角度来看，在我们的理解这种综合征的演变。然而，我们想指出的是，在考虑这种疾病时，应该包括一个由动物和人类数据支持的基本病理生理过程。特别是，作者讨论了钙稳态变化作为舒张期舒张异常和心肌僵硬发展的主要贡献者的重要性。病理性钙稳态的一个主要组成部分是横小管（TT）网络的重塑。TTs是心肌细胞中丰富折叠的膜结构，其含有钙（Ca 2+）信号微区。2-4同步的Ca 2+瞬变和兴奋-收缩耦合依赖于这些Ca 2+微区，这是在HFpEF中断的精确的建筑组织的维护。5-7即使在代偿性肥大阶段，也可在心肌中观察到TT变化。8，9在心力衰竭进展的连续过程中，在射血分数降低的心力衰竭中，甚至在HFpEF的情况下，TT表现出管腔扩张恶化和微区丢失。5，6，9此外，已经提出将不利的TT变化作为左心室辅助装置患者的预后工具，可以预测机械卸载后左心室功能恢复的可能性。10由于通过侵入性肌内膜活检检测TT完整性是不切实际的，cBIN 1（心脏桥接积分器1）正在成为一种反映TT重塑的非侵入性测试，因此有可能改变HFpEF诊断和预后的模式。cBIN 1是心肌细胞中的TT支架蛋白，其与TT健康成比例地转变为血液，在某种意义上允许心肌的液体活检。11，12我们小组最近进行的一项研究表明，在52例左心室射血分数保留的心肌病患者队列中，cBIN 1及其对数倒数衍生评分CS（cBIN 1评分）能够诊断心力衰竭人群，曲线下面积为0.98（95% CI，0.96-1.00）。12 CS提供了心力衰竭和对照人群的稳健分离。12此外，CS能够预测未来心血管住院超过1年的随访。12来自动物和人类研究的大量证据表明TT变化与HFpEF发病机制有关。因此，TT重塑是我们理解这种疾病和评估其受影响患者的重要前沿。
We would like to congratulate Pfeffer et al1 for their excellent review of the current state of knowledge of the complex syndrome of heart failure with preserved ejection fraction (HFpEF). The authors provide a comprehensive historical and epidemiological perspective on the evolution in our understanding of this syndrome. However, we would like to point out that there is a fundamental pathophysiological process supported by animal and human data that should be included when considering this disorder. In particular, the authors discuss the importance of calcium homeostatic changes as a major contributor to the development of diastolic relaxation abnormalities and myocardial stiffness. A major component of pathological calcium homeostasis is remodeling of the transverse tubule (TT) network. TTs are richly folded membrane structures in cardiomyocytes, which harbor calcium (Ca2+) signaling microdomains. 2–4 Synchrony of Ca2+ transients and excitation-contraction coupling are dependent on the maintenance of the precise architectural organization of theses Ca2+ microdomains, which are disrupted in HFpEF. 5–7 TT changes are observed in the myocardium even at the stage of compensated hypertrophy. 8, 9 In the continuum to heart failure progression, in heart failure with reduced ejection fraction and even with HFpEF, TTs exhibit worsening luminal dilation and microdomain loss. 5, 6, 9 Moreover, adverse TT changes have been proposed to serve as a prognostic tool in left ventricular assist device patients that can predict the potential for left ventricle functional recovery with mechanical unloading. 10 As it is impractical to assay TT integrity via invasive endomyocardial biopsies, cBIN1 (cardiac bridging integrator 1) is emerging as a noninvasive test that reflects TT remodeling and thus has the potential to change the paradigm of HFpEF diagnosis and prognosis. cBIN1 is a TT scaffolding protein in cardiomyocytes, which is turned over into blood in proportion to TT health, allowing in a sense a liquid biopsy of the myocardium. 11, 12 A recent study performed by our group demonstrated that in a cohort of 52 patients experiencing cardiomyopathies with preserved left ventricular ejection fraction, cBIN1 and its log inverse derived score CS (cBIN1 Score) are able to diagnose the heart failure population with an area under the curve of 0.98 (95% CI, 0.96–1.00). 12 CS provides a robust separation of the heart failure and control populations. 12 Additionally, CS is able to prognosticate future cardiovascular hospitalizations over 1 year of follow-up. 12 The accumulating body of evidence, from both animal and human studies, implicates TT changes in HFpEF pathogenesis. TT remodeling is, therefore, an important frontier in our understanding of this disease and our assessment of its affected patients.