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 »  Abstract
 » Introduction
 » Case Report
 » Discussion
 »  References
 »  Article Figures

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 Table of Contents    
DRUG WATCH
Year : 2019  |  Volume : 51  |  Issue : 6  |  Page : 413-415
 

Is there a place for angiotensin receptor-neprilysin inhibitors in the treatment of heart failure patients after heart transplantation?


1 Department of Cardiovascular Diseases, University Hospital “Sveti Duh”; University of Zagreb School of Medicine, Zagreb, Croatia
2 Department of Cardiovascular Diseases, University Hospital “Sveti Duh”, Zagreb, Croatia
3 Department of Cardiovascular Diseases, University Hospital “Sveti Duh”; Croatian Catholic University, Zagreb, Croatia

Date of Submission12-Feb-2019
Date of Acceptance23-Jul-2019
Date of Web Publication16-Jan-2020

Correspondence Address:
Dr. Dario Gulin
Department of Cardiovascular Diseases, University Hospital “Sveti Duh”, Sveti Duh 64, 10000 Zagreb
Croatia
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijp.IJP_562_18

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 » Abstract 


We present a case report of a heart failure patient after heart transplantation due to end-stage ischemic cardiomyopathy with significant clinical and echocardiographic improvement 3 months after the introduction of sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor. This new class of drugs is proved to be beneficial in heart failure patients, especially with reduced ejection fraction (HFrEF), but they have not yet been used in heart failure patients after heart transplantation. We believe that the increase of left ventricular systolic function, improvement of global longitudinal strain, and reduction of pulmonary hypertension with consequent clinical recovery in our patient may have been caused by sacubitril/valsartan.


Keywords: Heart failure, heart transplantation, sacubitril/valsartan


How to cite this article:
Gulin D, Planinic Z, Habek JC, Sikic J. Is there a place for angiotensin receptor-neprilysin inhibitors in the treatment of heart failure patients after heart transplantation?. Indian J Pharmacol 2019;51:413-5

How to cite this URL:
Gulin D, Planinic Z, Habek JC, Sikic J. Is there a place for angiotensin receptor-neprilysin inhibitors in the treatment of heart failure patients after heart transplantation?. Indian J Pharmacol [serial online] 2019 [cited 2020 Apr 8];51:413-5. Available from: http://www.ijp-online.com/text.asp?2019/51/6/413/276048





 » Introduction Top


Angiotensin receptor-neprilysin inhibitors (ARNIs) have been introduced in the past few years as a new class of drugs for the treatment of heart failure patients. Its benefits have been proven in randomized control trials in heart failure patients, mostly with reduced ejection fraction (HFrEF).[1],[2] Beside angiotensin receptor blocker (ARB), neprilysin inhibition with sacubitril augments beneficial counterregulatory systems resulting in increased levels of several endogenous vasoactive peptides (including natriuretic peptide, bradykinin, and adrenomedullin). Therefore, inhibition of both neprilysin and renin–angiotensin–aldosterone system is believed to be more effective than single angiotensin-converting enzyme inhibitor or single ARB therapy in heart failure patients.[1] Furthermore, recent studies reveal new indications and information about ARNI benefit in patients after myocardial infarction by reducing myocardial fibrosis and remodeling.[3] Treatment of heart failure in patients after heart transplantation is challenging with limitations in therapeutic possibilities. We present a case report of a heart failure patient after heart transplantation with significant clinical and echocardiographic improvement after sacubitril/valsartan introduction.


 » Case Report Top


A 56-year-old male patient, who had an orthotopic heart transplantation in 2014 due to end-stage ischemic cardiomyopathy, was hospitalized for acute heart failure with N-terminal pro B-type natriuretic peptide value of 4068 ng/L and 2-month history of worsening dyspnea, fatigue, and reduced exercise tolerance. These symptoms, in varying intensity, have been present since early after heart transplantation causing several heart failure hospitalizations over the years. Two-dimensional echocardiography examination in 2015, 1 year after heart transplantation, already showed globally hypokinetic left ventricle with reduced systolic function (EF: 35%), reduced right ventricle systolic function (tricuspid annular plane systolic excursion: 10 mm), and indirect signs of pulmonary hypertension (right ventricular systolic pressure [RVSP]: 59 mmHg). Endomyocardial biopsy was performed in 2016 and showed no evidence of rejection (Grade ISHLT-0R, according to the International Society for Heart and Lung Transplantation criteria).[4] Furthermore, there was no sign of cardiac allograft vasculopathy 0[5] on repeated coronary angiographies, last one being performed in 2017. During the last hospitalization, there was an echocardiographic deterioration showing a further reduction of left ventricle systolic function (EF: 29%), diffuse hypocontractility (Average global longitudinal peak systolic strain [GLPSavg] −4.1%) [Figure 1], and increase in pulmonary artery hypertension (RVSP: 65 mmHg). Along with immunosuppressive (cyclosporine and mycophenolate mofetil) and standard heart failure therapy, to improve cardiac function, sacubitril/valsartan was added into the treatment. At first, sacubitril/valsartan was started with the lowest dose of 24/26 mg twice a day, which was up titrated 2 weeks later to 49/51 mg twice a day. After 3 months, during regular follow-up, the patient was feeling much better with significantly improved physical activity tolerance. Clinically, there were no signs of peripheral edema, elevated jugular venous pressure, or pulmonary congestion on chest X-ray. Latest echocardiography examination showed surprising improvement of left ventricular systolic function (EF: 41%) and longitudinal myocardial deformation (GLPSavg − 7.4%) with reduction of pulmonary artery hypertension (RVSP: 50 mmHg) [Figure 2].
Figure 1: Echocardiography examination showing ejection fraction and global longitudinal strain before sacubitril/valsartan introduction

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Figure 2: Echocardiography examination showing ejection fraction and global longitudinal strain 3 months after sacubitril/valsartan introduction

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 » Discussion Top


ARNIs are proved to be effective in patients with heart failure, especially with reduced systolic function (HFrEF).[1] Heart transplantation is the treatment of choice for end-stage heart failure refractory to optimal medical therapy,[6] but there is no sufficient information for heart failure treatment after heart transplantation. We believe that sacubitril/valsartan addition into our patient's therapy may have caused heart failure symptoms relief and significant echocardiographic improvement of left ventricular systolic function, global longitudinal strain, and reduction of pulmonary hypertension. To our knowledge and available evidence-based literature, sacubitril/valsartan has not been used in heart failure patients after heart transplantation. Definitely, this requires further investigation to improve therapeutic possibilities for heart failure patients after heart transplantation.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin-converting enzyme inhibition in patients with chronic systolic heart failure: Rationale for and design of the prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF). Eur J Heart Fail 2013;15:1062-73.  Back to cited text no. 1
    
2.
Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC) Developed with the Special Contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016;37:2129-200.  Back to cited text no. 2
    
3.
von Lueder TG, Wang BH, Kompa AR, Huang L, Webb R, Jordaan P, et al. Angiotensin receptor neprilysin inhibitor LCZ696 attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy. Circ Heart Fail 2015;8:71-8.  Back to cited text no. 3
    
4.
Stewart S, Winters GL, Fishbein MC, Tazelaar HD, Kobashigawa J, Abrams J, et al. Revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant 2005;24:1710-20.  Back to cited text no. 4
    
5.
Mehra MR, Crespo-Leiro MG, Dipchand A, Ensminger SM, Hiemann NE, Kobashigawa JA, et al. International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010. J Heart Lung Transplant 2010;29:717-27.  Back to cited text no. 5
    
6.
Alraies MC, Eckman P. Adult heart transplant: Indications and outcomes. J Thorac Dis 2014;6:1120-8.  Back to cited text no. 6
    


    Figures

  [Figure 1], [Figure 2]



 

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