Management of severe heart failure in japan heart transplantation and lvad

1. Joint Symposium
ESC-Japanese Heart Failure Society
Treatment of Severe Heart Failure in Japan
Japanese Heart Failure Society
Tokyo Medical and Dental University
Mitsuaki Isobe

2. Conflict of Interest
I have nothing to disclose regarding
this presentation

3. Established 1996
2496 Members (Doctors, Nurses, other professionals)

4. Causes of Death in Japan and Europe
‘50 ‘60 ‘70 ‘80 ‘90 ‘00 ‘10
Neoplasm
Cardiac Dis
Pneumonia
Stroke
Cause of death
Japanese survey 2010
CHD
20%
Stroke
10%
Other CVD
12%
CHD
22%
Stroke
15%
Other CVD
15%
Men Women
European Cardiovascular Statistics 2012

5. HF in Japan
Patient number
Hospitalized patients with
Cardiovascular Disease
Cardiovascular
Gastrointestinal
HF
APHT
Arrhythmia
AMI
AD
National Survey
MHLW 2008
National Survey
MHLW 2008
Tsuchihashi-Makaya M, et al. Circ J 2009
HFrEF and HFpEF in
Japan
LVEF (%)
n＝1,692
250
200
0
150
100
50
～
9.9
5.0
～
14.9
10.0
～
19.9
15.0
～
24.9
20.0
～
29.9
25.0
～
34.9
30.0
～
39.9
35.0
～
44.9
40.0
～
49.9
45.0
～
54.9
50.0
～
59.9
55.0
～
64.9
60.0
～
69.9
65.0
～
74.9
70.0
～
79.9
75.0
～
84.9
80.0
～
85.0
Preserved
EF
Reduced
EF
26
％
16
％
58
％
40%
(人)

6. Causes of death for major cardiovascular disease in Japan
- Annual number -
MHLW, 1996-2012 Vital Statistics

7. Age distribution of CHF in Japan
Hamaguchi S, et al. Circ J 2011; 75: 2403-2410
0
120
100
40
0
(人)
80
60
20
Patientnumber
Age
100908070605040302010
n=2,675
71.0±13.4（
Mean±SD）
80>28.6％
908070605040
80.6%
National Survey
MHLW 2008
908070605040
Age
Estimated total number
of HF patients
Number of hospitalized
HF patients
J-CARE CARD

8. Elderly Population in the World
Heart Failure in Japan
(estimation)
Italia
UK
Greece
USA
Japan
SwedenFrance
Germany
0
200
300
500
600
800
700
400
100
NumberofPatients
（million）
1960 1970 1980 1990 2000 2020 2030204020502010
Heart Failure in US
National Health and Nutrition Examination Survey III, 1994
Okura, et al: Circ J, 2008
2025
2040

9. Tsutsui H, et al. Circ J 2007;71：449-454
Valvular
disease
Ischemic Heart
Disease
0 10 20 30 40 （％）
others
Hypertension
Cardiomyopathy
unknown
30％
35％
26％
15％
12％
5％
Causes of Heart Failure in Japan
－JCARE-GENERAL－

10. IHD HHD VHD DCM Others
SEOSI
（Italia）
0 20 40 60 80 100（％）
Framingham
（USA）
Etiology of Heart Failure in Europe and US

11. (Goda A, Isobe M, et al: Int Heart J, 2009)
１年後総死亡5.0%
心血管死亡4.5%
NYHA
Class IV HF
1year mortality:35%
Survival
βblocker (+) （n＝558）
βblocker (-) （n＝289）
1400120010008006004002000
0
0.2
0.4
0.6
0.8
1.0
Days
EventfreeSurvival
908070605040300
0.6
0.8
1.0
0.7
0.9
2010
HR 0.606
95%CI 0.377~0.974
P＝0.038
Log rank
P＜0.001
Tsuchihashi-Makaya ., Tsutsui. et al： Circ J 2010
Survival Rate of Heart Failure Patients in Japan
eGFR

12. Heart Transplantation and
Left Ventricular Assist Device
in Japan

13. Number of Heart Transplants in
Japan （2013.12.31）

14. Eurotransplant Registry
(8 countries)
Japanese Registry
Number of Waiting list vs Heart Transplant
total population=133 million total population=127 million
waiting time=approx. 3 years
(2012)

15. Heart transplant donors
per 1 million people in 2009
From Transplantation Procurement Management (TPM)
: International Registry Organ Donation and Transplantation

16. Days
Status１（～18）
Status１（18〜60)
Status２（～18)
Status２（18〜60）
Survival of patients who wait for
Heart Transplantation in Japan
・Status１：IV
catecholamine or LVADs
・Status２： no
catecholamine or LVADs
・Adult: age 18-60 yo
・Pediatric: age 0-17 yo

17. Survival rate after heart transplantation
Years after transplantation
Survivalrate
Heart transplantation in Japan
The International Society for
Heart and Lung Transplantation
• Strict selection of recipients by National committee
• Full coverage of medical cost by the government
• Difference in underlining heart disease

18. ISHLT
from 2006-2012
UNOS (USA)
Current USA Waiting List
Japanese Waiting
List
2013
Causes of HF waiting for transplant

19. Patients are waiting for Heart Tx under LVAD
Support
Implantable
VAD
Extracorporeal
VAD
No
VAD
Implantable VAD
Extracorporeal VAD
As of Jan 2014
26 participating
hospitals
Approval

20. Conclusions
• Heart failure is expanding throughout the world in
association with increase in elderly population.
• The largest contributors to the HF are IHD and HHD
irrespective of registries.
• Increase of heart transplant donor is an urgent
thema to save refractory HF patients.
• HF is a threat of industrialized societies and
cooperation among the ESC, AHA and JCS is a clue to
fight with this international threat.
• World-wide registry is necessary to investigate the
prognosis of HF in the real world.

22. Tsuchihashi-Makaya M, et al. Circ J 2009
HFrEF and HFpEF in
Japan
LVEF (%)
n＝1,692
250
200
0
150
100
50
～
9.9
5.0
～
14.9
10.0
～
19.9
15.0
～
24.9
20.0
～
29.9
25.0
～
34.9
30.0
～
39.9
35.0
～
44.9
40.0
～
49.9
45.0
～
54.9
50.0
～
59.9
55.0
～
64.9
60.0
～
69.9
65.0
～
74.9
70.0
～
79.9
75.0
～
84.9
80.0
～
85.0
Preserved
EF
Reduced
EF
26
％
16
％
58
％
40%
(人)
HFrEF and HFpEF in US
Fonarow GC, et al. J Am Coll Cardiol 2007; 50: 768-777
(人)
0~5
LVEF (％)
5,000
4,000
0
3,000
2,000
1,000
6~10
11~15
16~20
21~25
26~30
31~35
36~40
41~45
46~50
51~55
56~60
61~65
66~70
71~75
76~80
81~85
86~90
91~95
96~100
LVEF ≧ 40％：51.2％
LVEF > 50％：24.4％
– OPTIMIZE-HF –
HFrEF and HFpEF in Germany
– CARLA Study –
60.5% 39.5%
Tiller D et al. PLoS ONE 2013; 8: e59225
n＝86 n＝77
HFrEF HFpEF
42.7% 57.3%
HFrEF HFpEF

23. 東京医科歯科大学大学院
循環制御内科学教室
（循環器内科）

24. Waiting list vs number of heart transplant in Japan
（2013.12.31）

25. 心臓移植適応検討申請状況
植え込み型補助人工心臓認可
平均5.9例/月
（新規申請）
平均9.5例/月
（新規申請）

26. 心臓移植適応検討小委員会
• 委員長 1名、副委員長 2名、
• 幹事 3名（判定文作成等担当）、
• 評価委員 計 42名 （申請施設グループごとに計6グープ
に分け、評価を担当）
日本循環器学会
心臓移植委員会
心臓移植適応検討小委員会

27. Number of Heart Transplant,
Application and Waiting

28. Sato et al; Am Heart J. 2010;159:949-55
Gheorghiade M et al; Am J Med. 2006;119(12A):S3-10
Nieminen MS et al; Eur Heart J. 2006;27:2725-36
Comparison of comorbidities and etiology of ADHF
among Japan, USA and Europe
ATTEND(JAPAN, N=1110, 2010)
OPTIMIZE-HF(USA, N=48612, 2006)
EHFSⅡ(Europe, N=3580, 2006)

29. Patinets waiting for Heart Tx
under Mechanical Support
2015年3月31日現在 380名がネットワーク登録され待機中
Status 1:補助循環下もしくは
カテコラミンサポート下
Status 2:補助循環もしくはカテコ
ラミンサポートなく管理中の患者
Status 3:心臓移植に適さない全
身状態の患者

30. 植込型VAD認
可
国内移植
初例
臓器移植法改正
年別適応検討申請状況

31. ESC Guidelines: Heart Failure 2012
ACE-I(ARB)
β-blocker
MR antagonists
EF<35
HR>70
Ivabradine
QRS>120
CRT
NYHA II-IV
Diuretics
NYHA II-IV
NYHA II-IV and EF<35
LVAD/Tx
NYHA II-IV

32. Prescription for Heart Failure
Aldo P.Maggioni et al; Eur J Heart Failure(2010) 12,1076-1084
0 20 40 60 80 100
CCB
Aldosterone
blockers
Diuretics
Digitalis
βblockers
ACE-i/ARBs
ARB
ACE-i 64.9
27.0
88.5
86.7
20.6
（n=3,226）
82.8
43.7
9.9
βblockersβblockers
0 20 40 60 80 100
ACEI
ARB
Aldosterone
blockers
Diuretics
Digitalis
statin 23.1
28.7
66.0
45.9
44.2
45.9
（n=947）
CCB 17.1
88.1
(JCARE-CARD）
Tsutsui H, et al. Circ J 2007;71：449-454

33. ESC Guidelines: Heart Failure 2012
Diagnosis of HF by biomarkers
Statement from Japanese
Heart Failure Society on
BNP、NT-proBNP