- CLINICAL VIGNETTE
Sacubitril/valsartan as first-line therapy in anthracycline-induced cardiotoxicity
Rafał Dankowski1*, Wioletta Sacharczuk1*, Anna Łojko-Dankowska2, Anna Nowicka1, Anna Szałek-Goralewska1, Andrzej Szyszka1
12nd Department of Cardiology, Poznan University of Medical Sciences, Poznań, Poland
2Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznań, Poland
*Both authors equally contributed to the study
Correspondence to:
Rafał Dankowski, MD, PhD,
2nd Department of Cardiology,
Poznan University of Medical Sciences,
28 Czerwca 1956 194, 61–485 Poznań, Poland,
phone: +48 61 227 41 60,
e-mail: rafaldan@ump.edu.pl
Copyright by the Author(s), 2021
Kardiol Pol. 2021; 79 (9): 1040–1041; DOI: 10.33963/KP.a2021.0052
Received: April 25, 2021
Revision accepted: June 28, 2021
Published online: June 30, 2021
A 69-year-old female patient was admitted to the cardiology department due to a diagnosis of acute heart failure (AHF). She had a history of chemotherapy due to diffuse large B-cell lymphoma. The patient received the total anthracycline dose of 450 mg/m2. The last anthracycline chemotherapy was administered two months ago. The patient had no previous history of cardiovascular diseases. On admission, N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin I (hsTnI) levels were elevated (NT-proBNP: 5987 pg/ml; reference range <125 pg/ml; hsTnI: 74 pg/ml; reference range <14 pg/ml). Coronary angiography excluded vessel narrowing. Echocardiography showed moderate functional mitral regurgitation and severe left ventricular systolic dysfunction. Left ventricular ejection fraction (LVEF) was 24%, and global longitudinal strain (GLS) was 8.1% (Figure 1A).
Figure 1. Global longitudinal strain — bull’s-eye presentation. A. Baseline. B. Follow-up
A preliminary diagnosis of anthracycline-induced cardiotoxicity was made. The patient was treated initially with intravenous catecholamines and diuretics. After hemodynamic improvement catecholamines were stopped and intravenous diuretics were switched to oral torasemide 40 mg once daily (OD). Sacubitril/Valsartan (S/V) 24/26 mg twice a day (BID) and bisoprolol 2.5 mg OD were started. During the next few days, hypotension was observed. Bisoprolol was switched to ivabradine 5 mg BID, and diuretics were reduced. Enhanced superveillance including control of diuresis, creatinine, and potassium levels, allowed to maintain the S/V treatment (Table 1). The patient was discharged home with the diagnosis of heart failure with reduced ejection fraction (HFrEF) associated with anthracycline-induced cardiotoxicity. At discharge the patient was in New York Heart Association (NYHA) class III; a 6-minute walk test (6MWT) was 192 m.
Table 1. Pharmacological treatment, hemodynamics, and laboratory results of the patient during the hospitalization
|
|
Admission |
Day 1 |
Day 2 |
Day 3 |
Day 4 |
Day 5 |
Day 6 |
Day 7 |
Day 8 |
Discharge |
|
Treatment |
||||||||||
|
Catecholamines IV |
Start |
|
|
Stop |
|
|
|
|
|
|
|
Furosemide IV |
Start |
|
|
Stop |
|
|
|
|
|
|
|
Torasemide 40 mg OD |
|
|
|
Start |
Reduced (20 mg OD) |
|
|
|
|
|
|
Sacubitril/Valsartan 24/26 mg BID |
|
|
|
Start |
|
|
|
|
|
|
|
Ivabradine 5 mg BID |
|
|
|
|
|
Start |
|
|
|
|
|
Bisoprolol 2.5 mg OD |
|
|
Start |
|
Stop |
|
|
|
|
|
|
Hemodynamics |
||||||||||
|
Blood pressure, mm Hg Morning Evening |
92/78 102/76 |
109/81 104/78 |
111/69 103/77 |
106/73 97/62 |
87/54 91/62 |
93/69 92/65 |
99/67 92/68 |
97/58 91/52 |
101/71 97/59 |
102/61
|
|
Heart rate, beats/min Morning Evening |
107 104 |
80 101 |
85 88 |
79 78 |
99 88 |
79 89 |
76 69 |
82 74 |
60 72 |
73 71 |
|
Laboratory investigations |
||||||||||
|
Potassium, mmol/l |
5.1 |
4.6 |
3.9 |
4.1 |
4.6 |
|
4.3 |
|
4.5 |
|
|
Creatinine, µmol/l |
97.3 |
132.6 |
123.8 |
123.8 |
88.4 |
|
97.3 |
|
88.4 |
|
|
eGFR, ml/min/1.73m2 |
50.2 |
37.8 |
39.6 |
38.4 |
58.0 |
|
50.2 |
|
58.0 |
|
|
Diuresis, ml/24 h |
|
2500 |
2800 |
2600 |
2700 |
2900 |
3200 |
2300 |
|
|
Abbreviations: BID, twice daily; IV, intravenous; OD, once daily
After one month, the patient’s status was stable and S/V was increased to 49/51 mg BID. At the third-month follow-up the patient was in NYHA class II, and 6MWT distance increased to 384 m. The creatinine and potassium levels were stable, while NT-proBNP and hsTnI levels decreased to 865 pg/ml and 23 pg/ml, respectively. The left ventricular systolic function improved (LVEF, 42%, GLS, –10.2%; Figure 1B), and mitral regurgitation was only mild.
Our clinical vignette concerns the problem of anthracycline-induced myocardial injury. Cardiotoxicity due to anthracyclines may be acute, early, or late [1]. In our case, we observed the early type (i.e. <1 year since the anthracycline chemotherapy). The previous retrospective studies considered both — early and late types of anthracycline-induced cardiotoxicity as irreversible [2]. However, recent studies showed that early detection and adequate, guideline-directed heart failure treatment could stop or even reverse the progression of cardiac dysfunction [3, 4].
Our case demonstrates that S/V can be initiated immediately after achieving the patient’s hemodynamic stability. S/V was administered as the first-line therapy in our patient, instead of angiotensin-converting enzyme inhibitors. The essence of our observation is compliant with the results of the PIONEER-HF trial , which proved the safety and feasibility of early initiation of S/V therapy in hospitalized patients after the AHF episode [5]. Importantly, our case addresses also the central issue of S/V treatment — hypotension. We demonstrated that it could be effectively managed by reducing diuretics dose and switching from beta-blocker to ivabradine. We can conclude that S/V could be safely started as the first-line therapy in patients with anthracycline-induced cardiotoxicity.
Article information
Conflict of interest: AS, WS and RD received lecture honoraria from Novartis.
Open access: This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially. For commercial use, please contact the journal office at kardiologiapolska@ptkardio.pl.
How to cite: Dankowski R, Sacharczuk W, Łojko-Dankowska A, et al. Sacubitril/valsartan as first-line therapy in anthracycline-induced cardiotoxicity. Kardiol Pol. 2021; 79(9): 1040–1041, doi: 10.33963/KP.a2021.0052.
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