management of severe heart failure in japan heart transplantation and lvad

Joint SymposiumESC-Japanese Heart Failure Society

Treatment of Severe Heart Failure in Japan

Japanese Heart Failure SocietyTokyo Medical and Dental University

Mitsuaki Isobe

Conflict of Interest

I have nothing to disclose regarding this presentation

Established 19962496 Members (Doctors, Nurses, other professionals)

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

CHD20%

Stroke10%

Other CVD12%

CHD 22%

Stroke 15%

Other CVD 15%

Men Women

European Cardiovascular Statistics 2012

HF in JapanPatient number

Hospitalized patients with Cardiovascular Disease

Cardiovascular

Gastrointestinal

HF

APHTArrhythmia

AMIAD

National SurveyMHLW 2008

National SurveyMHLW 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)

Causes of death for major cardiovascular disease in Japan- Annual number -

MHLW, 1996-2012 Vital Statistics

Age distribution of CHF in Japan

Hamaguchi S, et al. Circ J 2011; 75: 2403-2410

0

120

100

40

0

(人)

80

60

20P

atient n

um

ber

Age

100908070605040302010

n=2,67571.0±13.4（Mean±SD）

80>28.6％

908070605040

80.6%

National SurveyMHLW 2008

908070605040

Age

Estimated total number of HF patients

Number of hospitalized HF patients

J-CARE CARD

Elderly Population in the WorldHeart Failure in Japan

(estimation)

Italia

UK

Greece

USAJapan

SwedenFrance

Germany0

200

300

500

600

800

700

400

100

Num

ber of Patients

（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

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－

IHD HHD VHD DCM Others

SEOSI（Italia）

0 20 40 60 80 100（％）

Framingham（USA）

Etiology of Heart Failure in Europe and US

(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 HF1year mortality:35%

Survival

βblocker (+) （n＝558）βblocker (-) （n＝289）

14001200100080060040020000

0.2

0.4

0.6

0.8

1.0

Days

Even

t fre

e Su

rviv

al

9080706050403000.6

0.8

1.0

0.7

0.9

2010

HR 0.60695%CI 0.377~0.974P＝0.038

Log rank P＜0.001

Tsuchihashi-Makaya ., Tsutsui. et al： Circ J 2010

Survival Rate of Heart Failure Patients in JapaneGFR

Heart Transplantation and Left Ventricular Assist Device

in Japan

Number of Heart Transplants in Japan （2013.12.31）

Eurotransplant Registry (8 countries) Japanese Registry

Number of Waiting list vs Heart Transplant

total population=133 million total population=127 millionwaiting time=approx. 3 years

(2012)

Heart transplant donors per 1 million people in 2009

From Transplantation Procurement Management (TPM): International Registry Organ Donation and Transplantation

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

Survival rate after heart transplantation

Years after transplantation

Surv

ival

rate

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

ISHLT from 2006-2012

UNOS (USA) Current USA Waiting List

Japanese Waiting List2013

Causes of HF waiting for transplant

Patients are waiting for Heart Tx under LVAD Support

Implantable VAD

Extracorporeal VAD

No VAD

Implantable VAD

Extracorporeal VAD

As of Jan 201426 participating hospitals

Approval

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.

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 ~ 1011 ~ 1516 ~ 2021 ~ 25

26 ~ 3031 ~ 3536 ~ 4041 ~ 4546 ~ 50

51 ~ 55

56 ~ 6061 ~ 6566 ~ 70

71 ~ 7576 ~ 8081 ~ 8586 ~ 9091 ~ 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

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）

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

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）

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

Number of Heart Transplant, Application and Waiting

Sato et al; Am Heart J. 2010;159:949-55Gheorghiade M et al; Am J Med. 2006;119(12A):S3-10Nieminen 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)

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

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

ESC Guidelines: Heart Failure 2012ACE-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

Prescription for Heart Failure

Aldo P.Maggioni et al; Eur J Heart Failure(2010) 12,1076-1084

0 20 40 60 80 100

CCB

Aldosteroneblockers

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

Aldosteroneblockers

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

ESC Guidelines: Heart Failure 2012Diagnosis of HF by biomarkers

Statement from Japanese Heart Failure Society on BNP、NT-proBNP