循環器ジャーナル68巻1号

2020年01月発行

特集 U40世代が描く心不全診療の現状と未来—基礎研究を識り，臨床を素心深考する Ⅰ．心筋症

—基礎編—拡張型心筋症のreversibilityの評価はどのようにされますか？

著者： 藤田寛奈¹

所属機関： ¹東京大学医学部附属病院循環器内科

ページ範囲：P.12 - P.18

Point
・基礎研究の進展とともに心不全発症進展にかかわる詳細な分子メカニズムが明らかになってきている．
・左室のリモデリングおよび心不全の発症進展には，背景としての遺伝子変異と，種々の負荷に対する心筋細胞および炎症細胞，内皮細胞，線維芽細胞，細胞外マトリクスなどが複合的に連関してもたらされる心筋の遺伝子発現およびその制御の変化，DNAダメージ，心筋の代謝状態の変化が関与する．
・分子病態に即した予後予測指標や新規の治療薬が見出されつつあり，今後の実用化およびより詳細な患者病態の層別化やそれに基づいた個別化医療の実現が期待される．

参考文献

1) Merlo M, Pyxaras SA, Pinamonti B, et al:Prevalence and prognostic significance of left ventricular reverse remodeling in dilated cardiomyopathy receiving tailored medical treatment. J Am Coll Cardiol 57:1468-1476, 2011

2) McNally E, Golbus JR, Puckelwartz MJ:Genetic mutations and mechanisms in dilated cardiomyopathy. J Clin Invest 123:19-26, 2013

3) Herman DS, Lam L, Taylor MR, et al:Truncations of titin causing dilated cardiomyopathy. N Engl J Med 366:619-628, 2012

4) Tobita T, Nomura S, Fujita T, et al:Genetic basis of cardiomyopathy and the genotypes involved in prognosis and left ventricular reverse remodeling. Sci Rep 8:1998, 2018

5) Dal Ferro M, Stolfo D, Altinier A, et al:Association between mutation status and left ventricular reverse remodelling in dilated cardiomyopathy. Heart 103:1704-1710, 2017

6) Ton VK, Vunjak-Novakovic G, Topkara VK:Transcriptional patterns of reverse remodeling with left ventricular assist devices:a consistent signature. Expert Rev Med Devices 13:1029-1034, 2016

7) Topkara VK. Chambers KT, Yang KC, et al:Functional significance of the discordance between transcriptional profile and left ventricular structure/function during reverse remodeling. JCI Insight 1:e86038, 2016

8) Halliday BP, Wassall R, Lota AS, et al:Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy（TRED-HF）:an open-label, pilot, randomised trial. Lancet 393:61-73, 2019

9) Nomura S, Satoh M, Fujita T, et al:Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure. Nat Commun 9:4435, 2018

10) Higo T, Naito AT, Sumida T, et al:DNA single-strand break-induced DNA damage response causes heart failure. Nat Commun 8:15104, 2017

11) Chang, ACY, Chang ACH, Kirillova A, et al:Telomere shortening is a hallmark of genetic cardiomyopathies. Proc Natl Acad Sci USA 115:9276-9281, 2018

12) Ko T, Fujita K, Nomura S, et al:Quantification of DNA Damage in Heart Tissue as a Novel prediction Tool for Therapeutic Prognosis of Patients With Dilated Cardio myopathy. JACC Basic Transl Sci, 2019 in press.

13) Diakos, NA, Navankasattusas S, Abel ED, et al:Evidence of Glycolysis Up-Regulation and Pyruvate Mitochondrial Oxidation Mismatch During Mechanical Unloading of the Failing Human Heart:Implications for Cardiac Reloading and Conditioning. JACC Basic Transl Sci 1 432-444, 2016

14) Kumar V, Santhosh Kumar TR, Kartha CC, et al:Mitochondrial membrane transporters and metabolic switch in heart failure. Heart Fail Rev 24:255-267, 2019

15) Chatfield KC, Sparagna GC, Chau S, et al:Elamipretide Improves Mitochondrial Function in the Failing Human Heart. JACC Basic Transl Sci 4:147-157, 2019

16) Nakayama T, Sugano Y, Yokoyama T, et al:Clinical impact of the presence of macrophages in endomyocardial biopsies of patients with dilated cardiomyopathy. Eur J Heart Fail 19:490-498, 2017

17) Jabbour A, Hayward CS, Keogh AM, et al:Parenteral administration of recombinant human neuregulin-1 to patients with stable chronic heart failure produces favourable acute and chronic haemodynamic responses. Eur J Heart Fail 13:83-92, 2011

18) Valiente-Alandi I, Potter SJ, Salvador AM, et al:Inhibiting Fibronectin Attenuates Fibrosis and Improves Cardiac Function in a Model of Heart Failure. Circulation 138:1236-1252, 2018