Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or OpenAthens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Free Access

Sacubitril/Valsartan in an Elderly Patient with Heart Failure: A Case Report

Cameli M. · Pastore M.C. · Pagliaro A. · Di Tommaso C. · Reccia R. · Curci V. · Mandoli G.E. · Mondillo S.

Author affiliations

Department of Cardiovascular Diseases, University of Siena, Siena, Italy

Corresponding Author

Matteo Cameli, MD, PhD

Department of Cardiovascular Diseases

University of Siena

IT-53100 Siena (Italy)

E-Mail matteo.cameli@yahoo.com

Related Articles for ""

Cardiology 2017;138(suppl 1):3-6

Abstract

Sacubitril/valsartan has recently been approved for the treatment of heart failure with reduced ejection fraction. Given its recent introduction in the armamentarium for the treatment of heart failure (HF), “field-practice” evidence is required to deepen the clinical management of sacubitril/valsartan therapy. We report a relevant case of an elderly patient who achieved major clinical benefits after only 3 months of sacubitril/valsartan therapy. Importantly, in our assessment, we employed speckle tracking echocardiography (STE), a recent echocardiography technique that is non-Doppler and not angle dependent, which analyzes deformations of heart chambers from standard images and allows a fast, reliable, and reproducible assessment of heart function. After 3 months of therapy, NHYA class decreased from III to I-II and hypertension was controlled. Echocardiography examination also showed a marked improvement, with a reduction of left ventricular diameter, improved diastolic function (E = 0.39 m/s; A 0.69 m/s; E/A 0.55), normalized diastolic function index (E/E' TDI = 6.93), normalized atrial volume (63 mL), and improved atrial strain (15.44%). This case report documents the fast clinical and symptom improvement with sacubitril/valsartan in an elderly patient with HF; comprehensive echocardiographic assessment, including STE, also revealed a marked functional improvement with this compound.

© 2017 S. Karger AG, Basel


Introduction

Sacubitril/valsartan (LCZ696, Entresto; Novartis, Basel, Switzerland) has been recently approved by the FDA and EMA for the treatment of heart failure (HF). It is the first molecule belonging to the class of angiotensin receptor-neprilysin inhibitors (ARNi): while valsartan blocks the angiotensin receptor, sacubitril inhibits neprilysin, an endopeptidase which cleaves natriuretic peptides [1].

The efficacy of sacubitril/valsartan in patients affected by HF with reduced ejection fraction (HFrEF) was demonstrated in the pivotal randomized PARADIGM-HF trial [2]. Moreover, the ongoing PARAGON-HF trial showed promising preliminary results [3]. Following the encouraging clinical results shown in well-designed studies, the recent guidelines for the treatment of HF issued by the European Society of Cardiology (ESC) recommended the use of ARNi instead of ACE inhibitors [4]. The recommended starting dosage is 49/51 mg, which is then titrated after 2-4 weeks. Adverse events with sacubitril/valsartan are rare, with hypotension being the most common [5].

Given its recent introduction in the armamentarium for the treatment of HF, “field practice” evidence is required to deepen the clinical management of sacubitril/valsartan therapy. In our daily practice, we can confirm the effectiveness and safety of this compound. In particular, we report here a relevant case of an elderly patient who achieved major clinical benefits after only 3 months of sacubitril/valsartan therapy.

Case Report

This case involves an 89-year-old man, who was referred to our cardiology unit before an intervention of vascular surgery (aneurism of abdominal aorta). The patient presented chronic ischemic heart disease (PTCA in 2000) and received a pacemaker in 2016. He also presented dyslipidemia, atheromatosis (abdominal aorta and carotids), hypertension (160/85 mm Hg), systolic murmur (2/6), diabetes, splenectomy, and kidney cirrhosis. The patient reported experiencing dyspnea on mild efforts, which corresponds to NYHA class II. No laboratory abnormalities were reported. The ECG showed a pacemaker rhythm of 64 bpm. The patient was under treatment with ACE inhibitors, furosemide 25 mg/day, potassium canreonate 50 mg/day, metformin, ASA, statins, and omega-3 fatty acids.

Echocardiography showed reduced left ventricular ejection fraction (35%), moderate mitral insufficiency (3+/4+), increased pulmonary pressure (45 mm Hg), increased ventricular diameter and thickness, and akinesia of interventricular septum. Therefore, the patient was diagnosed with HFrEF.

We decided to switch ACE inhibitor therapy to sacubitril/valsartan 49/51 mg b.i.d., following the actual indications for its prescription in patients with HFrEF.

After 3 weeks, echocardiography examination revealed impaired diastolic function (E = 0.97 m/s; A = 0.35 m/s; E/A = 2.77; E/E' = 17) in HFrEF and atrial volume of 115 mL (Fig. 1). Similar findings were reported with speckle tracking echocardiography (STE) (atrial strain: 8.91%). Clinical improvement became evident after 3 months of therapy with sacubitril/valsartan: NHYA class decreased to I-II and hypertension was controlled. Echocardiography examination also showed a marked improvement, with a reduction of left ventricular diameter, improved diastolic function (E = 0.39 m/s; A 0.69 m/s; E/A 0.55), normalized diastolic function index (E/E' TDI = 6.93), normalized atrial volume (63 mL), and improved atrial strain (15.44%) (Fig. 2).

Fig. 1

Echocardiographic assessment 3 weeks after the initiation of sacubitril/valsartan therapy: restricted Doppler pattern (a), E/E' = 17.48 (b), atrial volume: 115 mL (c), and atrial strain = 8.91% (d).

/WebMaterial/ShowPic/912420

Fig. 2

Echocardiographic assessment 3 months after the initiation of sacubitril/valsartan therapy: impaired distension Doppler pattern (a), E/E' = 6.93 (b), atrial volume: 63 mL (c), and atrial strain = 15.44% (d).

/WebMaterial/ShowPic/912419

Therapy with sacubitril/valsartan 49/51 b.i.d. was continued and a new evaluation was scheduled 3 months later.

Clinical Comment

We believe that the present case presents several aspects worthy of discussion. First, it documents the rapid improvement of a patient's clinical conditions following the initiation of sacubitril/valsartan therapy - which replaced prior treatment with ACE inhibitors. Moreover, it documents the improvement of diastolic and myocardial function with this drug, thus targeting the underlying mechanisms of HF [6]. Indeed, reduced myocardial distensibility increases filling pressure, thus impeding the maintenance of heart flow [7]. In this case, increased preload or peripheral blood pressure may have resulted in a further increase of central and venous pressure, leading to pulmonary edema [8]. Therefore, measuring filling pressure is of landmark importance in the management of HF.

Right heart catheterization represents the gold standard for the measurement of intracardiac pressure, and it allows to obtain a pressure-volume curve [9]. However, right heart catheterization is an invasive procedure and therefore it is usually replaced by echocardiography in clinical practice. With this latter method, filling pressure and modifications of heart structure can be estimated [10,11,12].

In our assessment, we employed STE, a recent echocardiography technique that is non-Doppler and not angle dependent, which analyzes deformations of heart chambers from standard images by a dedicated software. STE allows a fast, reliable, and reproducible assessment of heart function [13,14,15]. Atrial strain, estimated by STE, shows a good correlation with NYHA class [16] and NT-proBNP concentration [17]. Moreover, atrial strain correlates with pulmonary capillary wedge pressure [18,19].

In conclusion, this case report documents the fast clinical and symptom improvement with sacubitril/valsartan in an elderly patient with HF; comprehensive echocardiographic assessment, including STE, also revealed a marked functional improvement with this compound.

Acknowledgements

Editorial assistance for the preparation of this paper was provided by Luca Giacomelli, PhD, on behalf of Content Ed Net; this assistance was funded by Novartis.

Conflict of Interest

The authors have no conflict of interest to declare.


References

  1. Langenickel TH, Dole WP: Angiotensin receptor-neprilysin inhibition with LCZ696: a novel approach for the treatment of heart failure. Drug Discov Today Ther Strategy 2012;9:e131-e139.
    External Resources
  2. McMurray JJV, Packer M, Desai AS, et al; PARADIGM-HF Investigators and Committees: Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993-1004.
  3. Solomon SD, Rizkala AR, Gong J, Wang W, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, Van Veldhuisen DJ, Zannad F, Zile MR, Desai A, Shi VC, Lefkowitz MP, McMurray JJV: Angiotensin receptor neprilysin inhibition in heart failure with preserved ejection fraction: rationale and design of the PARAGON-HF trial. JACC Heart Fail 2017;5:471-482.
  4. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; Authors/Task Force Members; Document Reviewers: 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur J Heart Fail 2016;18:891-975.
  5. Fala L: Entresto (sacubitril/valsartan): first-in-class angiotensin receptor neprilysin inhibitor FDA approved for heart failure. Am Health Drug Benefits 2016;9(Spec Feature):78-82.
    External Resources
  6. Nichimura RA, Tajik AJ: Evaluation of diastolic filling of left ventricle in health and disease: Doppler echocardiography is the clinician's Rosetta stone. J Am Coll Cardiol 1997;30:8-18.
  7. Zile MR, Brutsaert DL: New concepts in diastolic dysfunction and diastolic heart failure. Part I. Diagnosis, prognosis, and measurements of diastolic function. Circulation 2002;105:1387-1393.
  8. Gaasch WH, Zile MR: Left ventricular diastolic dysfunction and diastolic heart failure. Annu Rev Med 2004;55:373-394.
  9. Paulus WJ, Tschope C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbely A, Edes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL: How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J 2007;28:2539-2255.
  10. Cameli M, Mandoli GE, Loiacono F, Dini FL, Henein M, Mondillo S: Left atrial strain: a new parameter for assessment of left ventricular filling pressure. Heart Fail Rev 2016;21:65-76.
  11. Yamada H, Klein AL: Diastology 2010: clinical approach to diastolic heart failure. J Echocardiogr 2010;8:65-79.
  12. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelisa A: Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiograph 2009;10:165-193.
  13. Cameli M, Caputo M, Mondillo S, Ballo P, Palmerini E, Lisi M, Marino E, Galderisi M: Feasibility and reference values of left atrial longitudinal strain imaging by two-dimensional speckle tracking. Cardiovasc Ultrasound 2009;7:6.
  14. Vianna-Pinton R, Moreno CA, Baxter CM, Lee KS, Tsang TS, Appleton CP: Two-dimensional speckle-tracking echocardiography of the left atrium: feasibility and regional contraction and relaxation differences in normal subjects. J Am Soc Echocardiogr 2009;22:299-305.
  15. Ahmed MK, Soliman MA, Reda AA, Abd El-Ghani RS: Assessment of left atrial deformation properties by speckle tracking in patients with systolic heart failure. Egypt Heart J 2015;67:199-208.
    External Resources
  16. Sanchis L, Gabrielli L, Andrea R, Falces C, Duchateau N, PerezVilla F, Bijnens B, Sitges M: Left atrial dysfunction relates to symptom onset in patients with heart failure and preserved left ventricular ejection fraction. Eur Heart J Cardiovasc Imaging 2015;16:62-67.
  17. Kurt M, Tanboga IH, Aksakal E, Kaya A, Isik T, Ekinci M, Bilen E: Relation of left ventricular end-diastolic pressure and N-terminal pro-brain natriuretic peptide level with left atrial deformation parameters. Eur Heart J Cardiovasc Imaging 2012;13:524-530.
  18. Cameli M, Sparla S, Losito M, Righini FM, Menci D, Lisi M, D'Ascenzi F, Focardi M, Favilli R, Pierli C, Fineschi M, Mondillo S: Correlation of left atrial strain and Doppler measurements with invasive measurement of left ventricular end diastolic pressure in patients stratified for different values of ejection fraction. Echocardiography 2016;33:398-405.
  19. Cameli M, Lisi M, Mondillo S, Padeletti M, Ballo P, Tsioulpas C, Bernazzali S, Maccherini M: Left atrial longitudinal strain by speckle tracking echocardiography correlates well with left ventricular filling pressures in patients with heart failure. Cardiovasc Ultrasound 2010;8:14.

Author Contacts

Matteo Cameli, MD, PhD

Department of Cardiovascular Diseases

University of Siena

IT-53100 Siena (Italy)

E-Mail matteo.cameli@yahoo.com


Article / Publication Details

First-Page Preview
Abstract of  

Published online: December 21, 2017
Issue release date: December 2017

Number of Print Pages: 4
Number of Figures: 2
Number of Tables: 0

ISSN: 0008-6312 (Print)
eISSN: 1421-9751 (Online)

For additional information: https://www.karger.com/CRD


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Langenickel TH, Dole WP: Angiotensin receptor-neprilysin inhibition with LCZ696: a novel approach for the treatment of heart failure. Drug Discov Today Ther Strategy 2012;9:e131-e139.
    External Resources
  2. McMurray JJV, Packer M, Desai AS, et al; PARADIGM-HF Investigators and Committees: Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371:993-1004.
  3. Solomon SD, Rizkala AR, Gong J, Wang W, Anand IS, Ge J, Lam CSP, Maggioni AP, Martinez F, Packer M, Pfeffer MA, Pieske B, Redfield MM, Rouleau JL, Van Veldhuisen DJ, Zannad F, Zile MR, Desai A, Shi VC, Lefkowitz MP, McMurray JJV: Angiotensin receptor neprilysin inhibition in heart failure with preserved ejection fraction: rationale and design of the PARAGON-HF trial. JACC Heart Fail 2017;5:471-482.
  4. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; Authors/Task Force Members; Document Reviewers: 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur J Heart Fail 2016;18:891-975.
  5. Fala L: Entresto (sacubitril/valsartan): first-in-class angiotensin receptor neprilysin inhibitor FDA approved for heart failure. Am Health Drug Benefits 2016;9(Spec Feature):78-82.
    External Resources
  6. Nichimura RA, Tajik AJ: Evaluation of diastolic filling of left ventricle in health and disease: Doppler echocardiography is the clinician's Rosetta stone. J Am Coll Cardiol 1997;30:8-18.
  7. Zile MR, Brutsaert DL: New concepts in diastolic dysfunction and diastolic heart failure. Part I. Diagnosis, prognosis, and measurements of diastolic function. Circulation 2002;105:1387-1393.
  8. Gaasch WH, Zile MR: Left ventricular diastolic dysfunction and diastolic heart failure. Annu Rev Med 2004;55:373-394.
  9. Paulus WJ, Tschope C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbely A, Edes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL: How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J 2007;28:2539-2255.
  10. Cameli M, Mandoli GE, Loiacono F, Dini FL, Henein M, Mondillo S: Left atrial strain: a new parameter for assessment of left ventricular filling pressure. Heart Fail Rev 2016;21:65-76.
  11. Yamada H, Klein AL: Diastology 2010: clinical approach to diastolic heart failure. J Echocardiogr 2010;8:65-79.
  12. Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelisa A: Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiograph 2009;10:165-193.
  13. Cameli M, Caputo M, Mondillo S, Ballo P, Palmerini E, Lisi M, Marino E, Galderisi M: Feasibility and reference values of left atrial longitudinal strain imaging by two-dimensional speckle tracking. Cardiovasc Ultrasound 2009;7:6.
  14. Vianna-Pinton R, Moreno CA, Baxter CM, Lee KS, Tsang TS, Appleton CP: Two-dimensional speckle-tracking echocardiography of the left atrium: feasibility and regional contraction and relaxation differences in normal subjects. J Am Soc Echocardiogr 2009;22:299-305.
  15. Ahmed MK, Soliman MA, Reda AA, Abd El-Ghani RS: Assessment of left atrial deformation properties by speckle tracking in patients with systolic heart failure. Egypt Heart J 2015;67:199-208.
    External Resources
  16. Sanchis L, Gabrielli L, Andrea R, Falces C, Duchateau N, PerezVilla F, Bijnens B, Sitges M: Left atrial dysfunction relates to symptom onset in patients with heart failure and preserved left ventricular ejection fraction. Eur Heart J Cardiovasc Imaging 2015;16:62-67.
  17. Kurt M, Tanboga IH, Aksakal E, Kaya A, Isik T, Ekinci M, Bilen E: Relation of left ventricular end-diastolic pressure and N-terminal pro-brain natriuretic peptide level with left atrial deformation parameters. Eur Heart J Cardiovasc Imaging 2012;13:524-530.
  18. Cameli M, Sparla S, Losito M, Righini FM, Menci D, Lisi M, D'Ascenzi F, Focardi M, Favilli R, Pierli C, Fineschi M, Mondillo S: Correlation of left atrial strain and Doppler measurements with invasive measurement of left ventricular end diastolic pressure in patients stratified for different values of ejection fraction. Echocardiography 2016;33:398-405.
  19. Cameli M, Lisi M, Mondillo S, Padeletti M, Ballo P, Tsioulpas C, Bernazzali S, Maccherini M: Left atrial longitudinal strain by speckle tracking echocardiography correlates well with left ventricular filling pressures in patients with heart failure. Cardiovasc Ultrasound 2010;8:14.