Organoprotective effects of serelaxin in patients with severe decompensated heart failure
Abstract
Serelaxin (recombinant molecule of the human relaxin-2) is an innovative drug for the treatment of acute heart failure. Preclinical and clinical studies demonstrated the ability of serelaxin to relieve the symptoms of heart failure, provide a significant reduction in congestion and have a protective effect on the heart, kidneys, liver. 48-hour serelaxin infusion in patient with ischemic cardiomyopathy and severe decompensated heart failure with cardio-hepatic syndrome led to significant regression of systemic congestion (evaluated by physical signs and by bioimpedance vector analysis), the improvement of structural and functional state of the myocardium (evaluated by standard echocardiography and global systolic longitudinal deformation of the left ventricle with speckle tracking echocardiography), regression of cardio-hepatic syndrome, improvement of renal function. Serelaxin therapy was well tolerated and was safe. Presented case report demonstrates beneficial effects of serelaxin on the heart failure symptoms and the organoprotective effects.
About the Authors
Z. D. Kobalava
Peoples’ Friendship University of Russia
Russian Federation
Vavilova ul. 61, Moscow, 117292
Russian Federation
Vavilova ul. 61, Moscow, 117292
S. V. Villevalde
Peoples’ Friendship University of Russia
Russian Federation
Vavilova ul. 61, Moscow, 117292
Russian Federation
Vavilova ul. 61, Moscow, 117292
A. E. Solov'jova
Peoples’ Friendship University of Russia
Russian Federation
Vavilova ul. 61, Moscow, 117292
Russian Federation
Vavilova ul. 61, Moscow, 117292
I. A. Merai
Peoples’ Friendship University of Russia;
City Clinical Hospital №64
Russian Federation
Vavilova ul. 61, Moscow, 117292
Russian Federation
Vavilova ul. 61, Moscow, 117292
References
1. Moin D.S., Bloom M.W., Papadimitriou L., Butler J. Serelaxin for the treatment of heart failure. Expert Review of Cardiovascular Therapy 2016;14(6):667-75
2. Tietjens J., Teerlink J.R. Serelaxin and acute heart failure Heart 2016;102:95-99.
3. Raleigh J.M., Toldo S., Das A., Abbate A., Salloum F. Relaxin' the Heart: A Novel Therapeutic Modality. J Cardiovasc Pharmacol Ther. 2016;21(4):353-62.
4. Teerlink J.R., Cotter G., Davison B.A. et al. Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet 2013;381:29-39.
5. Cotter G., Milo O., Davison B.A. Increased mortality after an acute heart failure episode: new pathophysiological insights from the RELAX-AHF study and beyond. Curr Heart Fail Rep 2014;11(1):19-30.
6. Kovaleva G.V., Sutygina T.Yu., Koroleva L.Yu., Mironov N.N. Case report of post-MI reccurrent left ventricular failure management with Serelaxine-recombinant human relaxin-2 (Reasanz, Novartis) Kardiologija i serdechno-sosudistaja hirurgija, 2015;8(5):92-94. Russian (Ковалева Г.В., Сутыгина Т.Ю., Королёва Л.Ю., Миронов Н.Н. Клинический случай лечения рецидивирующей острой левожелудочковой недостаточности нафоне острогоинфаркта миокарда серелаксином—рекомбинантным препаратом человеческого релаксина-2 (Реасанз, NOVARTIS) Кардиология и сердечно-сосудистая хирургия 2015;8(5):92-94.7.
7. Shpagina L.A., Surovenko T.N., Panacheva L.A., Loktin E.M., Kohno V.N., Elizarova N.L., Kotova O.S., Rukavitsina A.A., Rogovskih W.Yu. Experience With the Use of Serelaxin for Acute Right Ventricular Failure Due to Pulmonary Embolism in Patients With Acute Ischemic Stroke. Kardiologija 2016;56(2):68-72. Russian. (Шпагина Л.Д., Суровенко Т.Н., Паначева Л.А., Локтин Е.М., Кохно В.Н., Елизарьева Н.Л., Котова О.С., Рукавицына А.А., Роговских В.Ю. Опыт применения серелаксина для лечения острой правожелудочковой недостаточности при тромбоэмболии легочной артерии в условиях острого нарушения мозгового кровообращения Кардиология. 2016;56(2):68-72)
8. Zhirov I.V., Nasonova S.N., Tereshchenko S.N., Nikolaeva O.A., Uskach T.M. Clinical case of usage of serelaxin in the patient with acute decompensated heart failure. Russian Journal of Cardiology 2016;132(4):83-88. Russian (Жиров И.В., Насонова С.Н., Терещенко С.Н., Николаева О.А., Ускач Т.М. Клинический опыт применения серелаксина у пациента с острой декомпенсацией хронической сердечной недостаточности Российский кардиологический журнал 2016;132(4): 83-88))
9. Shpagina L.A., Panacheva L.A., Loctin E.M., Pospelova T.I., Kotova O.S., Kokhno V.N., Rukavitsina A.A. An experience of serelaxine use for acute heart failure in patients with oncohematological diseases Cardiovascular Therapy and Prevention 2015;14(3):35-38. Russian (Шпагина Л.А.,Паначева Л.А., Локтин Е.М., Поспелова Т.И., Котова О.С., Кохно В.Н., Рукавицына А.А. опыт применения серелаксина при острой сердечной недостаточности у больных с онкогематологическими заболеваниями Кардиоваскулярная терапия и профилактика. 2015;14(3):35-38)
10. Jelinic M., Leo C.H., Post Uiterweer E.D. et al. Localization of relaxin receptors in arteries and veins, and region-specific increases in compliance and bradykinin-mediated relaxation after in vivo serelaxin treatment. FASEB J. 2014;28:275-287
11. Danielson L.A., Sherwood O.D., Conrad K.P. Relaxin is a potent renal vasodilator in conscious rats. J Clin Invest. 1999;103(4):525-533
12. Smith M.C., Danielson L.A., Conrad K.P., Davison JM. Influence of recombinant human relaxin on renal hemodynamics in healthy volunteers. J Am Soc Nephrol. 2006;17(11):3192-3197
13. Chow B.S. et al. Relaxin requires the angiotensin II type 2 receptor to abrogate renal interstitial fibrosis. Kidney Int. 2014:86:75-85
14. Http://www.medscape.com/viewarticle/863962#vp_1
15. Boehnert M.U., Armbruster F.P., Hilbig H. Relaxin as a protective substance in the preserving solution for liver transplantation: spectrophotometric in vivo imaging of local oxygen supply in an isolated perfused rat liver model. Ann N Y Acad Sci 2009;1160:320-321
16. Metra M, Cotter G, Davison BA et al. RELAX-AHF Investigators. Effect of serelaxin on cardiac, renal, and hepatic biomarkers in the Relaxin in AcuteHeart Failure (RELAX-AHF) development program: correlation with outcomes. J Am Coll Cardiol 2013;61:196-206
17. Samuel CS, Cendrawan S, Gao XM, Ming Z, Zhao C, Kiriazis H, Xu Q, Tregear GW, Bathgate RA, Du XJ. Relaxin remodels fibrotic healing following myocardial infarction. Lab Invest 2011;91:675-690.
18. Perna AM, Masini E, Nistri S, Briganti V, Chiappini L, Stefano P, Bigazzi M, Pieroni C, Bani Sacchi T, Bani D. Novel drug development opportunity forrelaxin in acute myocardial infarction: evidences from a swine model. FASEB J 2005;19:1525-1527.
19. Nistri S, Cinci L, Perna AM, Masini E, Mastroianni R, Bani D. Relaxin induces mast cell inhibition and reduces ventricular arrhythmias in a swine model of acute myocardial infarction. Pharmacol Res 2008;57:43-48.
20. Billebeau G, Prud’homme M, Sadoune M. et al. Effects of serelaxin on a systolic cardiac dysfunction induced by isoproterenol in mice with increased cardiac aldosterone. European Journal of Heart Failure 2016,18(Suppl. 1),8
21. Parikh A, Patel D, Mctiernan CF, et al. Relaxin suppresses atrial fibrillation by reversing fibrosis and myocyte hypertrophy and increasing conduction velocity and sodium current in spontaneously hypertensive rat hearts. Circ Res 2013;113:313-321
For citation:
Kobalava Z.D., Villevalde S.V., Solov'jova A.E., Merai I.A. Organoprotective effects of serelaxin in patients with severe decompensated heart failure. Rational Pharmacotherapy in Cardiology. 2016;12(4):414-423. (In Russ.) https://doi.org/10.20996/1819-6446-2016-12-4-414-423
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