Жамият ва инновациялар –
Общество и инновации –
Society and innovations
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Effective influence of sacubitril/valsartan on systolic function of
left ventricle in patients with heart failure and a reduced ejеction
fraction
Ikbol ADILOVA
1
, Gulnoza AKBAROVA
2
Republican Scientific-Practical Center of Sports Medicine
Tashkent State Stomatology Institute
ARTICLE INFO
ABSTRACT
Article history:
Received March 2021
Received in revised form
20 March 2021
Accepted 15 April 2021
Available online
20 May 2021
Aim: We evaluated the influence of sacubitril/valsartan on the
left ventricle function and clinical status of patients with heart
failure and a reduced ejection fraction.
Materials and methods: From 2018 to 2020, patients cured
with 50-200 mg sacubitril/valsartan after coronary bypass
grafting or coronary stenting for ischemic heart disease and
HFrEF (aged 54-70 years) were enrolled in this prospective
study.
Results: There was no death case. There was a female
prevalence with female to male ratio of 1,7:1. the value of
ejection fraction high significantly increased(p=0,035), whereas
the indices of left ventricle end-diastolic volume(p=0,015) and
end-diastolic volume index (p=0,022) as well as left ventricle
mass index were high significantly decreased(p=0,001) that
indicate the amelioration of left ventricle systolic function.
Correspondingly, the clinical status of all patients improved
according to New York Heart Association Class (p=0,001).
Conclusion: The post-CABG or PCI patients with HFrEF should
be cured with sacubitril/valsartan basingon its implementation
instruction. Nevertheless, future studies should focus on a larger
cohort of post-CABG or PCI patients to compare the effectiveness
and safety of sacubitril/valsartan usage raising from its adverse
event in comparison to conventional therapy.
2181-1415/© 2021 in Science LLC.
This is an open access article under the Attribution 4.0 International
(CC BY 4.0) license (https://creativecommons.org/licenses/by/4.0/deed.ru)
Keywords:
sacubitril/valsartan;
neprilysin,
reduced ejection fraction,
heart failure,
left ventricle.
1
Doctor of Philosophy, Republican Scientific-Practical Center of Sports Medicine, Tashkent, Uzbekistan.
E-mail: ikbol.adilova@mail.ru.
2
Doctor of Philosophy, Tashkent State Stomatology Institute, Tashkent, Uzbekistan.
E-mail: bakolli19@mail.ru.
Жамият ва инновациялар – Общество и инновации – Society and innovations
Special Issue – 4 (2021) / ISSN 2181-1415
747
Юрак етишмовчилиги ва паст фракцияли беморларда
сакубитрил/валсартан чап қоринча систолик функциясига
эффективли таъсири
АННОТАЦИЯ
Калит сўзлар:
сакубутрил/валсартан;
неприлизин,
пасайган қискариш
фракцияси,
юрак етишмовчилиги,
чап қоринча.
Мақсад: сакубутрил/валсартаннинг юрак етишмовчилиги
ва пасайган қисқариш фракцияси билан булган беморларнинг
чап қоринчаси столик функциясига ва клиник ҳолатига
таъсирини баҳолаш.
Материаллар ва методлар: 2018–2020 йй. мобайнида илмий
тадқиқотга коронар шунтлаш еки стентлашдан кейин 50-200
мг сакубитрил/валсартан билан даволанган беморлар (54-70
ёш) жалб этилди.
Натижалар: ўлим асорати қайд етилмади. Аёлларнинг
эркакларга нисбати 1,7:1 ни ташкил етди. Чап қоринча
қисқариш фракцияси статистик ахамиятли даражада
пасайди
(р=0,035).
Якуний
диастолик
ҳажми
кўрсаткичлари (р=0,015) ва якуний диастолик ҳажми
индекси (р=0,022), шунингдек, чап қоринча масса индекси
статистик ахамиятли даражада камайганлиги (р=0,001) чап
қоринча
систолик
функциясини
яхшилаганлигини
билдиради. Ҳамда, барча беморларнинг NYHA бўйича
клиник ҳолатияхшиланди (р=0,001).
Хулоса: юрак етишмовчилиги ва юрак қисқариш
фракцияси паст булган беморлар коронар шунтлаш ёки
стентлашдан
кейин
сакубитрил/валсартан
билан
даволаниши
мақсадга
мувофиқ.
Бироқ,
келажакда
тадқиқотлар коронар шунтлаш еки стентлашни куздан
кечирган
купроқ
беморларда
сакубитрил/валсартан
самарадорлигини ва хавфсизлигини уларнинг салбий
таъсиридан келиб чиққан ҳолда анъанавий даво услуби
билан таққослашга қаратилган булиши керак.
Эффективное
влияние
сакубитрил/валсартана
на
систолическую функцию левого желудочка у пациентов с
сердечной недостаточностью и низкой фракцией выброса
АННОТАЦИЯ
Ключевые слова:
сакубитрил/валсартан;
неприлизин,
сниженная фракция
выброса,
сердечная
недостаточность,
левый желудочек.
Цель: оценка влияния сакубитрил/валсартана на
функцию левого желудочка и клинический статус
пациентов с сердечной недостаточностью и сниженной
фракцией выброса.
Материалы и методы: с 2018 по 2020 гг. в проспективное
исследование были включены пациенты, излечившиеся с
помощью сакубитрил/валсартана в дозе 50-200 мг после
АКШ или ЧКВ по поводу ишемической болезни сердца и
сердечной недостаточности с низкой фракцией выброса
(в возрасте 54-70 лет).
Жамият ва инновациялар – Общество и инновации – Society and innovations
Special Issue – 4 (2021) / ISSN 2181-1415
748
Результаты: летальный исход не был отмечен.
Соотношение
женщин
и
мужчин
составило
1,7: 1. Значение высокой фракции выброса достоверно
увеличилось (p = 0,035), тогда как показатели конечного
диастолического объема левого желудочка (p = 0,015) и
индекса конечного диастолического объема (p = 0,022), а
также индекса массы левого желудочка статистически
значимо уменьшились (p = 0,001), что свидетельствует об
улучшении систолической функции левого желудочка.
Соответственно, клинический статус всех пациентов
улучшился по классу NYHA (p = 0,001).
Заключение: пациенты с сердечной недостаточностью и
сниженной фракцией выброса после АКШ или ЧКВ должны
лечиться сакубитрил/валсартаном в соответствии с
инструкциями по его применению. Тем не менее, будущие
исследования должны быть сосредоточены на более
широкой когорте пациентов, перенесших АКШ или ЧКВ,
чтобы сравнить эффективность и безопасность применения
сакубитрил/валсартана в отношении его побочных
действий в сравнение с традиционной терапией.
INTRODUCTION
Approximately 7% among all leading causes of the overall morbidity in Uzbekistan
attributed to chronic heart failure [1]. As known, over the last 20 years the rate of
morbidity and mortality is diminished in patients with heart failure with reduced ejection
fraction (HFrEF) by means of medications targeted the renin–angiotensin–aldosterone
system [2, 3]. As previously reported, several efforts to potentially benefit patients with
HFrEF due to the rise of the activity of natriuretic peptides (NPs) have failed until a large
(n=8442 patients), phase III, randomized, controlled clinical trial (PARADIGM-HF) which
highlighted the advantageous results of sacubitril/valsartan regarding decrease
the risk of
cardiovascular death and hospitalization for heart failure by 20% and
16% less risk for
death from any cause as compared with enalapril (p<0,001) [4]. As shown in figure 1,
sacubitril/valsartan (formerly known as LCZ696) is a first-in-class angiotensin receptor
neprilysin inhibitor (ARNI) that simultaneously suppresses RAAS activation through
blockade of angiotensin II type 1 receptors and enhances vasoactive peptides including
NPs through inhibition of neprilysin, the enzyme responsible for their degradation [5, 6].
As a result, ARNI combined with angiotensin II receptor antagonist contribute to the
neurohormonal balanced influence on vasodilation and vasoconstriction. Nevertheless,
the influence of sacubitril/valsartan on systolic function of left ventricle (LV) after
coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) less
studied that we aimed at handling with it.
Жамият ва инновациялар – Общество и инновации – Society and innovations
Special Issue – 4 (2021) / ISSN 2181-1415
749
Fig 1. A mechanism of the balanced effect of
sacubitril/valsartan on vasodilation and
vasoconstriction.
MATERIALS AND METHODS
A prospective observational study conducted on 30 patients after coronary bypass
grafting or coronary stenting for ischemic heart disease and HFrEF, aged between 54 and
70 years, who were investigated in out-patient department of
Republican Scientific-
Practical Center of Sports Medicine
and treated with 50
-200 mg
sacubitril/valsartan
(Yuperio
TM
; Novartis Pharma services, Switzerland
)
between December 2018 and
December 2020.
The inclusion criterion of
HFrEF
patients was the post-CABG or coronary
stenting states. The informed consent was obtained from the patient’s next of kin. Patient
demographics are given in Table 1.
Table 1.
Patient demographics (n=30).
Variable
n (%) or mean ± SD
Age (years)
63,0±4,72
Sex (F/M)
19/11(63,6/36,4)
Hypertension
27 (90,9)
Postinfarction cardiosclerosis
22 (72,7)
Diabetes
16(54,5)
*Post CABG
13 (43,3)
*Post CS
17(56,7)
Mitral regurgitation I degree
13(43,3)
Mitral regurgitation II degree
3(10,0)
*RBBB
11 (36,4)
*CABG –
coronary artery bypass grafting, *
CS
–
coronary stenting, *
RBBB –
right
bundle branch block
.
Жамият ва инновациялар – Общество и инновации – Society and innovations
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Statistical analysis. Data were processed by using SPSS 19.0 statistical analysis
software. The quantitative data were expressed as the mean and standard deviation (SD)
,
respectively.Continuous variables were compared using t test and the rank-sum tests.
P<0,05 was considered statistically significant, whereas P<0,001 was highly significant.
RESULTS
There was a female prevalence with female to male ratio of 1,7
:1
. A mean follow-up
period was 2,1±0,5 years. At the final follow-up examination, neither readmission to clinic
due to exacerbation of heart failure nor death case was registered. As seen in table 2, the
echocardiographic signs of mild and moderate ischemic mitral regurgitation were
high
significantly
disappeared
(
p=0,001
)
. Correspondingly, the value of ejection fraction
high
significantly
raised
(
p=0,035
)
, whereas the indices of left ventricle end-diastolic
volume
(
p=0,015
)
and end-diastolic volume index
(
p=0,022
)
as well as left ventricle mass
index were high significantly dropped
(
p=0,001
)
that indicate the amelioration of left
ventricle contractility. As a result, the clinical status of all patients improved according to
New York Heart Association Class
(
p=0,001
)
.
Table 2.
Comparative echocardiographic results of left ventricle function and clinical status before
and after
sacubitril/valsartan introduction
(n=30).
Parameters
Before
medication
After medication
P
Secondary mitral
regurgitation, n (%)
Mild
18 (60,0)
0
0,001
Moderate
14 (4,67)
0
0,001
Ejection fraction (%)
42,54±5,02
51,54±4,41
0,035
Left ventricle contractility-hypokinesia, n (%)
19(63,3)
2(6,7)
0,001
Left ventricle end-diastolic volume, ml
200,72±50,66
114,75±22,45
0,015
Left ventricle end-diastolic volume index,
ml/m
2
115,84±2,93
88,93±2,13
0,022
Left ventricle mass index, gr/m
2
123,03±48,46
95,27±25,41
0,001
*NYHA class, n (%)
I
1 (3,3)
0
0,001
II
27 (90)
10 (33,3)
0,001
III
2 (6,6)
0
0,001
*NYHA –
New York Heart Association.
DISCUSSION
As previously reported, chronic heart failure resulting in depressed ejection fraction
of left ventricle has been considered as a frequent cause of death not only in older but also
in young patients [7-10].
Of particular interest, a
randomized, controlled clinical trial (PARADIGM-HF)
showed that 21 (0,2%) patients of all 8442 needed treatment with sacubitril/valsartan
instead of enalapril for 27 months to prevent one death from a cardiovascular cause or
hospitalization for HF.
Fonarow et al. reported that
approximately 28,484 deaths (range
18,230
-
41,017) could be prevented yearly with optimal usage of ARNI/ARBs therapy
instead of ACEIs/ARBs that may accelerate more implementation of ARNI/ARBs [11].
Жамият ва инновациялар – Общество и инновации – Society and innovations
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751
Accordingly,
the 2017 update of the American College of Cardiology/ American Heart
Association/Heart Failure Society of America (ACC/AHA/HFSA) guideline for HF
management included
ARNI/ARBs
, along with ACEIs and ARBs, as a treatment to reduce
mortality and morbidity in HFrEF
[11, 12]
.
The results of De Vecchis et al. retrospective study demonstrated the reduction of
mortality rate at 6 months (OR 0,14; 95% CI 0,04-0,50) and HF hospitalization (OR 0,03;
95% CI 0,01-0,14) in patients treated with sacubitril/valsartan versus conventional
therapy
[13]
. Furthermore, according to some studies’ data, adverse events profile for
sacubitril/valsartan is similar to that of
ACEIs/ARBs [13, 14].
To the best of our knowledge, previous studies are scarce regarding the evaluation
of
sacubitril/valsartan
influence on left ventricle geometry and function in
HFrEF
patients
after CABG or PCI and mostly have focused on ischemic heart disease but non-operated
patients. Thus, our goal in this study is to facilitate research on the aforementioned effect
of
sacubitril/valsartan
treatment
.
Though competing in the past, conservative therapy with
sacubitril/valsartan
should not be opposed to other treatment strategy comprising ACE inhibitor usage [15,
16]. This study was conducted to better define the place of
sacubitril/valsartan
introduction
in the armamentarium to treat patients with chronic heart failure after
coronary bypass grafting or stenting. As identified in this study, the post-CABG or PCI
patients with depressed ejection fraction are considered as appropriate candidates for the
abovementioned therapy.
The results of our experience are coexistent with previous studies regarding the
effect of
sacubitril/valsartan implementation on left ventricle systolic function and
absence of both readmissions due to clinical worsening and death.
CONCLUSION
To summarize,
sacubitril/valsartan
may reduce the rate of rehospitalization due to
the clinical deterioration as well as death rate in these candidates. Thus, our findings
suggest that the post-CABG or PCI patients with
HFrEF
should be placed on
sacubitril/valsartan
treatment according to its implementation instruction. Nevertheless,
confirmation of the clinical usefulness and safety of latter treatment concerning it adverse
events compared to ACEIs/ARBs requires further studies in a larger cohort of post-CABG
or PCI patients.
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