JURNAL KEDOKTERAN DIPONEGORO

(DIPONEGORO MEDICAL JOURNAL)

Online : http://ejournal3.undip.ac.id/index.php/medico
E-ISSN : 2540-8844
DOI: 10.14710/dmj.v12i3.38665
JKD (DMJ), Volume 12, Number 3, May 2023 : 167-172

Mochamad Ali Sobirin, Kelly Kuswidiyanto, Yan Herry, Sodiqur Rifqi, Hiroyuki Tsutsui

THE COMPARISON OF CLINICAL CHARACTERISTICS OF ACUTE

DECOMPENSATED HEART FAILURE PATIENTS BETWEEN JCARE-CARD JAPAN
AND DR. KARIADI HOSPITAL REGISTRY

Mochamad Ali Sobirin1*, Kelly Kuswidiyanto2, Yan Herry1, Sodiqur Rifqi1, Hiroyuki Tsutsui3,4
1Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Diponegoro, Semarang, Indonesia
2Department of Cardiology and Vascular Medicine, Cilacap General Hospital, Cilacap, Indonesia
3Department of Cardiovascular Medicine, Faculty of Medical Science, Kyushu University, Japan
4School of Medicine and Graduate School, International University of Health and Welfare, Japan

* Corresponding Author : E-mail: [email protected]

ABSTRACT
Background: Heart failure (HF) is a significant public health issue because of its high prevalence, dismal prognosis, and
high financial burden caused by frequent hospitalizations and extensive care. Low socioeconomic status has been linked
to an increased incidence of HF, and different regions and races may have varied clinical characteristics of HF patients.
Asian nations Indonesia and Japan both have varying socioeconomic conditions that could affect clinical characteristics
and outcomes. The differences between HF patients from Indonesia and Japan in terms of clinical characteristics and
outcomes have not been previously investigated. Objective: To investigate demographic and clinical characteristics of HF
patients in Indonesia and compare with Japanese registry. Methods: In this retrospective observational study, patients
presenting with acute decompensated heart failure (ADHF) at dr. Kariadi Hospital (RSDK) were consecutively recruited
during 2014-2015 hospitalization period. Baseline data including demographic, clinical characteristics, laboratory data on
admission, medication use before hospitalization, and length of stay during hospitalization were collected from medical
record using the form of the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD). The descriptive
analysis was performed to compare those HF characteristics. Results: A total of 246 ADHF patients in RSDK registry
were included with average of age of subjects was 56.4 years-old and 57.3% were male. Etiology was predominantly
ischemic heart disease (IHD) in 60.6%, average left ventricular ejection fraction 40.1% and length of hospital stay was 8.8
days. Compared to Japanese registry, the characteristics of clinical status and laboratory data on admission were almost
similar between studies except for higher prevalence of ischemic heart disease, renal dysfunction and dyslipidemia but
lower prior stroke in RSDK study. The average length of stay at hospital was longer in Japanese registry (8.8 days vs. 33.9
days). Conclusion: Ischaemic heart disease and renal dysfunction more prevalent in RSDK registry, but prior stroke and
length of stay at hospital higher in Japanese registry of hospitalized ADHF patients.
Keywords: Acute Decompensated Heart Failure, Clinical Characteristics, Registry, Length of Stay

INTRODUCTION Worryingly, Hawkins et reported that low

Heart failure (HF) is a clinical syndrome as the socioeconomic status was linked with increased
final stage of a variety of diseases that attack the heart incidence of HF in both community and hospital
organ. The main manifestations are shortness of settings and due to the increased risk of a significant
breath and fatigue, which limits physical activity, as risk factor for heart diseases like coronary artery
well as fluid accumulation, leading to pulmonary disease, hypertension, and diabetes mellitus (DM),
congestion and peripheral edema. Due to the high the prevalence of HF is anticipated to be equal to the
frequency, poor prognosis, and significant financial proportion in developed nations.4 Meanwhile in
burden associated with healthcare, HF has emerged Japan, a developed nation, as shown in a study by
as a significant health issue in Western countries over Okura et al. predicted that the number of patients with
the past ten years..1,2 Indonesia and Japan are left ventricular dysfunction (LVD) will increase to 1.3
demographic Asian countries but have different million in 2030, causing a heart failure pandemic.5
socioeconomic characteristics which may affect Moreover, recent reports have shown a dramatic
guideline-directed therapy and clinical outcomes. In increase in the prevalence of heart failure patients
Indonesia, The Government Basic Health Research with an ischemic etiology compared to previous
(Riskesdas) 2007 with 968,997 respondents in 440 studies, it approaches the prevalence observed in
districts of 33 provinces showed that the proportion Western subjects, accounting for 50–60%.6 Little is
of patients with HF based on symptoms was 0.31%.3 known about the impact of these differences on the

167
 JURNAL KEDOKTERAN DIPONEGORO
(DIPONEGORO MEDICAL JOURNAL)
Online : http://ejournal3.undip.ac.id/index.php/medico
E-ISSN : 2540-8844
DOI: 10.14710/dmj.v12i3.38665
JKD (DMJ), Volume 12, Number 3, May 2023 : 167-172

Mochamad Ali Sobirin, Kelly Kuswidiyanto, Yan Herry, Sodiqur Rifqi, Hiroyuki Tsutsui

use of evidence-based heart failure treatments and its such as valvular heart disease, and dilated
outcomes in Asian countries with different cardiomyopathy was similar between studies.
socioeconomic statuses, such as Indonesia and Japan. The comorbidities were also similar between
Therefore, this study aimed to describe and compare studies such as hypertension (50–60%), diabetes
the clinical characteristics of heart failure patients mellitus (25–30%), except prior stroke being lower in
hospitalized with exacerbation of heart failure RSDK studies (6.0%) than those in Japanese studies
symptoms in Indonesia and Japan. 16.3%). However, the prevalence of renal dysfunction
(28.4% vs. 11.3%) and dyslipidemia (46.8% vs.
METHODS 25.8%) were higher in RSDK studies.
This descriptive study compared and studied
retrospectively the demographic characteristics and Clinical status on admission
treatments in patients hospitalized with worsening The mean heart rate, systolic blood pressure
HF in dr. Kariadi Hospital (RSDK), Semarang, (SBP) and diastolic blood pressure (DBP) were
Indonesia and prospectively in Japan using the same similar between studies. Laboratory data such as
form of the Japanese Cardiac Registry of Heart sodium electrolyte and hemoglobin were similar
Failure in Cardiology (JCARE-CARD).7 In this between studies except for higher serum creatinine
study, we analyzed the acute phase data of (1) level in RSDK registry. Plasma B-type natriuretic
characteristics (age, sex, cause of HF, and medical peptide (BNP) was higher on admission in RSDK
history), (2) admission vital signs and laboratory data (collected in small numbers) compared to Japanese
(blood chemistry and echocardiogram), (3) medical studies (data not shown) which also showed more
drug use (angiotensin-converting enzyme [ACE] severe heart failure in RSDK registry (Table 2).
inhibitor, angiotensin II receptor blocker [ARB], β
blocker, diuretics, digitalis, calcium channel blocker, Table 1. Patient characteristics COPD, chronic obstructive
aspirin, and statin), (4) length of stay. There were a pulmonary disease; HF, heart failure
Characteristics RSDK Registry JCARE-CARD
total of 1677 and 246 patients in Japan and Indonesia, (n= 246) Japan
respectively. (n= 1677)
Age, yrs (mean ± SD) 56.4 ± 13.0 70.7 ± 13.5
RESULTS Male, % 57.3 59.4
Causes of HF,%
Ischemic 60.6 34.0
Patient characteristics Valvular 20.3 28.1
The average age of the 246 studied patients was Hypertensive 37.8 26.4
56.4 ± 13.0 years and 57.3% were men (Table 1). The Dilated cardiomyopathy 8.1 17.0
Medical history, %
causes of HF were mostly due to ischemic heart Hypertension 61.2 52.1
disease in 60.6% and or hypertensive heart disease in Diabetes mellitus 32.4 29.8
37.8%, valvular heart disease in 20.3%, and dilated Dyslipidemia 46.8 25.8
cardiomyopathy in 8.1%. Risk factors for ischemic Prior stroke 6.0 16.3
heart disease (IHD) included hypertension (61.2%), Renal dysfunction 36.0 11.3
Anemia 45.6 20.3
diabetes mellitus (32.4%), and dyslipidemia (46.8%). COPD 7.2 5.8
Approximately one-thirds of the patients had a Prior hospitalization (HF) 28.4 50.0
history of prior hospitalization due to HF.
Patient characteristics in this study were Medication use before hospitalization was also
compared with those in JCARE-CARD Japan (Table compared between studies. The use of ACE
1). The mean age was younger in RSDK 56.3 ± 12.8 inhibitors/ARBs (48.4% vs. 55.4%), and β blockers
years old. Males were predominant sharing 57-60% (21.1% vs. 22.3%) was similar between studies, but
in both studies. Ischemic heart disease, some with the choice of using ACE inhibitors was slightly lower
concomitant hypertensive heart disease, was the most in RSDK registry (13.0% vs. 26.5%) (Table 2). The
predominant cause of HF, but it was higher in RSDK use of calcium channel blockers and aspirin before
(65.3% vs 34.0%). The prevalence of other causes hospitalization admission was lower in the RSDK
registry, but, the use of aldosterone antagonist was

168
 JURNAL KEDOKTERAN DIPONEGORO
(DIPONEGORO MEDICAL JOURNAL)
Online : http://ejournal3.undip.ac.id/index.php/medico
E-ISSN : 2540-8844
DOI: 10.14710/dmj.v12i3.38665
JKD (DMJ), Volume 12, Number 3, May 2023 : 167-172

Mochamad Ali Sobirin, Kelly Kuswidiyanto, Yan Herry, Sodiqur Rifqi, Hiroyuki Tsutsui

higher in RSDK study than Japanese study (59.3%

and 24.1%). 15

Length of stay 10
The average length of stay was 8.8 ± 6.7 days

Day
in the present study. It was much longer in Japanese
study (33.9 ± 34.9 days). Median length of stay 5
reported in JCARE-CARD RSDK and Japan is
shown in Fig. 1. The most striking difference was 0
longer length of stay in Japanese study (15 days vs. JCARE-CARD JCARE-CARD
7 days). RSDK Japan

Table 2. Vital signs, laboratory data and medication use on Figure 1. Median Length of Stay (days)
admission
Characteristics RSDK JCARE-CARD
Registry Japan DISCUSSION
(n= 246) (n= 1677) In the present study, using the JCARE-CARD
Vital signs database, the characteristics, clinical status, and
Heart rate, bpm 91.1 ± 19.0 87.8 ± 24.4 laboratory data at the admission of patients
SBP, mmHg 125.3 ± 23.3 134.3 ± 30.3
DBP, mmHg 79.4 ± 15.3 75.4 ± 18.2
hospitalized with acute decompensated heart failure
Laboratory Data were almost the same between studies, except for a
Serum creatinine, 1.81 ± 1.56 1.28 ± 1.03 higher prevalence of ischemic heart disease, renal
mg/dl dysfunction, and dyslipidemia but lower prior stroke
BUN, mg/dl 26.5 ± 19.1 26.2 ± 16.7 in RSDK study. Management was also similar except
Na, mequiv/L 139.9 ± 4.8 139.7 ± 4.6
Hemoglobin, g/dL 12.7 ± 2.1 12.4 ± 4.5 for the higher use of ACE inhibitors and lower use of
LVEF, % 40.1 ± 19.2 42.5 ± 17.9 aldosterone antagonists in the Japanese study. The
Medication Use most surprising difference between RSDK and the
ACE inhibitor, % 13.0 26.5 Japanese study was the longer length of stay in Japan.
ARB, % 35.4 28.9
Βeta blocker, % 21.1 22.3
The clinical characteristics of patients
Diuretics, hospitalized due to HF were almost similar between
Loop diuretics,% 54.9 54.4 RSDK and Japan study, even with previous large
Aldosterone 59.3 24.1 studies such as ATTEND (acute decompensated heart
antagonist, % failure syndromes) registry,8 ADHERE (Acute
Digitalis, % 34.1 26.6
CCB, % 6.5 24.2 Decompensated Heart Failure National Registry),9
Aspirin, % 22.8 34.5 OPTIMIZE-HF (Organized Program to Initiate
Statin, % 23.6 16.2 Lifesaving Treatment in Hospitalized Patients with
Heart Failure),10 EHFS-II (Euro Heart Failure Survey
SBP, systolic blod pressure; DBP, diastolic blood II).11 This patient similarity may be due to the
pressure; LVEF, left ventricular ejection fraction; inclusion of only hospitalized patients with
ACE, angiotensin converting enzyme; ARB, exacerbated heart failure, which may also include
angiotensin receptor blocker; CCB, calcium channel patients with somewhat uniform conditions on
blockers admission. However, the prevalence of ischemic heart
disease (IHD) in JCARE-CARD Japan (34%) was
lower than that in the RSDK study (approximately
60%), and the prevalence was similar in Western
countries. Interestingly, Shiba et al reported a trend of
westernization from CHART-2 study that showed
IHD was the most prevalent cause of HF reaching
53%, this has led many experts to speculate that the
apparent trend toward increasing prevalence of CAD

169
 JURNAL KEDOKTERAN DIPONEGORO
(DIPONEGORO MEDICAL JOURNAL)
Online : http://ejournal3.undip.ac.id/index.php/medico
E-ISSN : 2540-8844
DOI: 10.14710/dmj.v12i3.38665
JKD (DMJ), Volume 12, Number 3, May 2023 : 167-172

Mochamad Ali Sobirin, Kelly Kuswidiyanto, Yan Herry, Sodiqur Rifqi, Hiroyuki Tsutsui

as a cause of heart failure is due to: (1) the number of Ultimately, concomitant patients with stroke and HF
CAD patients is increasing due to the accelerating have higher mortality rates, more severe neurological
westernization of Japanese lifestyles. (2) recent deficits, and longer hospital stays than those without
therapeutic advances have dramatically increased the HF.17 The study found that the higher rate of
number of survivors of acute coronary events.5 experiencing stroke in Japan may be due to the higher
Meanwhile, the prevalence of stroke was higher in proportion of older people, and the rate of
Japan than in the RSDK study. These differences, hemorrhagic stroke is thought to be twice as high in
therefore, suggest that there are still clinical features Japan as in Western countries.18
of heart failure patients that may vary by region and The longer stay in Japan compared to the RSDK
race. study may be due to differences in the medical
HF patients in the RSDK study had a similarly system, continued management of comorbidities, and
low rate of beta-blocker usage before hospitalization intensive management of risk factors during
compared to the Japan study (21.1% vs. 22.8%) hospitalization due to worsening heart failure. Longer
despite the beneficial effect of beta-blockers on heart hospital stays may increase opportunities for
failure patients. Angiotensin-converting enzyme optimizing management and are known to improve
(ACE) inhibitors/angiotensin receptor blockers outcomes in HF patients.19 Unfortunately, as the
(ARBs) and beta-blockers are known to improve nature of HF patients, it is known for the high rates
outcomes in patients with chronic heart failure for hospitalization, recurrence and treatment that in
secondary to left ventricular systolic dysfunction, and the United States (U.S.) the expenses reaching 39
recent European Society of Cardiology (ESC) billion dollars per year.20 In the other hand, despite
guidelines for the treatment of HF stated that both fewer length of stay in RSDK patients, there was low
beta-blockers and ACE inhibitors should be started as usage of standard medication i.e. beta blocker that
soon as possible after diagnosis of heart failure with could affect the recurrence rate for admission and
reduced ejection fraction (HFrEF).12 ACE inhibitors survival which is worse in low socioeconomic status
have moderate effects on left ventricular remodeling, as concluded by Hawkins et al.4 Therefore, it is
whereas β-blockers often lead to marked extremely important to move forward so that patients
improvements in EF. In addition, beta-blockers have receive the best possible care (including education)
antiischemic effects and are probably more effective and access to multidisciplinary HF teams.
in reducing the risk of sudden cardiac death, leading
to a significant and earlier reduction in all-cause CONCLUSION
mortality. The Euro Heart Failure Study also found The characteristics, clinical status, and laboratory
that heart failure medications, especially beta- data on admission in patients hospitalized with ADHF
blockers, were underused and inappropriately low were similar between dr. Kariadi Hospital (RSDK)
when prescribed.13 This may be a throwback to the and Japan registry, except for higher ischemic
past, when beta-blockers were considered etiology, renal dysfunction and dyslipidemia in
contraindicated in patients with left ventricular RSDK, but higher prior stroke in Japan which might
dysfunction.14 This study also revealed that patients contribute to the longer length of stay in Japan.
in RSDK had a lower rate of ACE inhibitor use and
higher use of ARBs, similar to the Japan study. ETHICAL APPROVAL
Regarding the association between heart failure This study was reviewed and approved by The
and stroke, a population-based cohort study by Ethics Commission of the Faculty of Medicine,
Adelborg et al. reported that heart failure patients had Universitas Diponegoro, and dr. Kariadi Hospital
a higher risk of not only ischemic stroke, but also all Semarang, Indonesia, with approval number:
stroke subtypes, than the general population.15 After 909/EC/FK-RSDK/IX/2016.
a first stroke, women were 25 times more likely to
have a major adverse cardiac event, including heart CONFLICTS OF INTEREST
attack, heart failure, and cardiovascular death, and The authors declare no conflict of interest
men without apparent heart disease were 23 times
more likely to have MACE 30 days later.16

170
 JURNAL KEDOKTERAN DIPONEGORO
(DIPONEGORO MEDICAL JOURNAL)
Online : http://ejournal3.undip.ac.id/index.php/medico
E-ISSN : 2540-8844
DOI: 10.14710/dmj.v12i3.38665
JKD (DMJ), Volume 12, Number 3, May 2023 : 167-172

Mochamad Ali Sobirin, Kelly Kuswidiyanto, Yan Herry, Sodiqur Rifqi, Hiroyuki Tsutsui

FUNDING 9. Adams KF Jr., Fonarow GC, Emerman CL, et al.

This study received funding from Sumitomo 2005. ADHERE Scientific Advisory Committee
Foundation Grant Japan Related Research Project and Investigators. Characteristics and outcomes of
patients hospitalized for heart failure in the United
ACKNOWLEDGMENTS Stated: rationale, design, and preliminary
This work was supported by the Department of observations from the first 100,000 cases in the
Cardiology and Vascular Medicine, Faculty of Acute Decompensated Heart Failure National
Medicine, Universitas Diponegoro. Survey (ADHERE). Am Heart J. 149:209-216.
10. Fonarow, G.C., Abraham, W.T., Albert, et al.
REFERENCES 2008. Day of admission and clinical outcomes for
1. Jessup M, Brozena S. 2003. Heart Failure. N Engl patients hospitalized for heart failure: findings
J Med. 348:2007-2018. from the Organized Program to Initiate Lifesaving
2. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Treatment in Hospitalized Patients With Heart
Byun JJ, Colvin MM. 2022 AHA/ACC/HFSA Failure (OPTIMIZE-HF). Circ Heart Fail. 1: 50–
Guideline for the Management of Heart Failure: 57
A Report of the American College of 11. Nieminen, M.S., Brutsaert, D., Dickstein, K., et al.
Cardiology/American Heart Association Joint 2006. EuroHeart Failure Survey II (EHFS II): a
Committee on Clinical Practice Guidelines. survey on hospitalized acute heart failure patients:
Circulation. 2022 May 3;145(18):e895-e1032. description of population. Eur Heart J. 27: 2725–
3. Delima, Mihardja L, Sumartono W, et al. 2008. 2736
Laporan Akhir: Prevalensi dan faktor determinan 12. McDonagh TA, Metra M, Adamo M, Gardner RS,
penyakit jantung di Indonesia (Analisis lanjut Baumbach A, Böhm M, et al. ESC Scientific
data Riskesdas 2007). Puslitbang Biomedis dan Document Group. 2021 ESC Guidelines for the
Farmasi, Depkes RI. diagnosis and treatment of acute and chronic heart
4. Hawkins NM, Jhund PS, McMurray JJ, Capewell failure. Eur Heart J. 2021 Sep 21;42(36):3599-
S. 2012. Heart failure and socioeconomic status: 3726. doi: 10.1093/eurheartj/ehab368. Erratum in:
accumulating evidence of inequality. Eur J Heart Eur Heart J. 2021 Oct 14;: PMID: 34447992
Fail. Feb;14(2):138-46 13. Komajdaa M, Follath F, Swedberg K et al.; The
5. Okura Y, Ramadan MM, Ohno Y, et al. 2008. Study Group of Diagnosis of the Working Group
Impending endemic: future projection of heart on Heart Failure of the European Society of
failure in Japan to the year of 2055. Circ J. Cardiology. The EuroHeart Failure Survey
72:489-491. programme – a survey on the quality of care
6. Shiba N, Nochioka K, Miura M, et al. 2011. Trend among patients with heart failure in Europe. Part
of westernization of etiology and clinical 2: treatment. Eur Heart J 2006;27:2725–36.
characteristics of heart failure patients in Japan. 14. Laxman Dubey, Paul Kalra, Henry Purcell. 2013.
Circ J. 75:823-833. Underuse of beta blockers in patients with heart
7. Hamaguchi S, Kinugawa S, Tsuchihashi-Makaya failure. Br J Cardiol. 20:11–13
M, et al. 2013. Characteristics, management, and 15. Adelborg K, Szépligeti S, Sundbøll J, Horváth-
outcomes for patients during hospitalization due Puhó E, Henderson VW, Ording A, et al. Risk of
to worsening heart failure-A report from the stroke in patients with heart failure: a population-
Japanese Cardiac Registry of Heart Failure in based 30-year cohort
Cardiology (JCARE-CARD). J Cardiol. study. Stroke. 2017;48:1161–1168
Aug;62(2):95-101 16. Sposato L.A, Lam M, Allen B, Shariff S.Z,
8. Sato, N, Kajimoto, K, Asai, K., et al. 2010. Acute Saposnik G. First-ever ischemic stroke and
decompensated heart failure syndromes incident major adverse cardiovascular events in 93
(ATTEND) registry. A prospective observational 627 older women and men. Stroke. 2020; : 387-
multicenter cohort study: rationale, design, and 394
preliminary data. Am Heart J. 159: 949–955 17. Haeusler KG, Laufs U, Endres M. Chronic heart
(e941) failure and ischemic

171
 JURNAL KEDOKTERAN DIPONEGORO
(DIPONEGORO MEDICAL JOURNAL)
Online : http://ejournal3.undip.ac.id/index.php/medico
E-ISSN : 2540-8844
DOI: 10.14710/dmj.v12i3.38665
JKD (DMJ), Volume 12, Number 3, May 2023 : 167-172

Mochamad Ali Sobirin, Kelly Kuswidiyanto, Yan Herry, Sodiqur Rifqi, Hiroyuki Tsutsui

stroke. Stroke. 2011;42:2977–2982

18. Suzuki, K., Izumi, M. The incidence of
hemorrhagic stroke in Japan is twice compared
with western countries: the Akita stroke
registry. Neurol Sci . 2015; 36, 155–160.
https://doi.org/10.1007/s10072-014-1917-z
19. Gheorghiade, M. and Pang, P.S. Acute heart
failure syndromes. J Am Coll Cardiol. 2009; 53:
557–573
20. Bui AL, Horwich TB, Fonarow GC, et al. 2011.
Epidemiology and risk profile of heart failure.
Nature Reviews Cardiology. 8:30-41.

172