Differences in clinical characteristics and its effect for outcomes

Byung Su Yoo, MD., PhD.

Division of Cardiology, Wonju College of Medicine,

Yonsei University, South Korea

Differences in clinical characteristics

and its effect for outcomes

between western and Korean patients

with ADHF :

ACC 2015: Advances in the care of patients with heart failure

Outlines : What’s difference ?

Background

Comparisons of Acute Heart Failure Registry

Outcomes and other clinical analysis

Summary

: the prevalence of heart failure has been rapidly increasing in worldwide and its

influence on mortality, morbidity and the cost of health care is growing fast.

Heart failure is epidemic in worldwide

Heart

Failure ↑

Aging

Society

Advanced medical & surgical

care

IHD, DM etc.

Background

Comparisons of HF prevalence

Estimated Prevalence of heart failure by age group

(National Health Insurance Service’s sample cohort

database, 2010, Korea).

Prevalence of heart failure by sex and age (National

Health and Nutrition Examination Survey: 2009–

2012). Source: National Center for Health Statistics

and National Heart, Lung, and Blood Institute. USA

0.8

3.8

9.4

0.8

4.7

9.5

0

2

4

6

8

10

40-59 60-79 80+

Pre

va

len

ce

Age

Men Women

0.2

1.5

6.6

10.6

0.6 1.2

4.8

13.5

0

2

4

6

8

10

12

14

16

20-39 40-59 60-79 80+

Pre

va

len

ce

of P

op

ula

tio

n

Age (Years)

Background

Trends of heart failure in Korea Heart failure is rapidly increasing, especially in old age

2009 y 2010 y 2011 y 2012 y 2013 y

Total 94,421 100,480 109,588 114,393 115,063

Male 32,989 36,334 41,010 42,935 44,330

Female 61,432 64,146 68,578 71,458 70,733

(number of total HF patients)

Total 0-9 YO 10-19 YO 20-29 YO 30-39 YO 40-49 YO 50-59 YO 60-69 YO 70-79YO ≥80 YO

Male 176 3 3 8 25 70 338 462 1,179 2,744

Female 285 3 3 7 22 52 159 506 1,622 3,362

(number of HF patients per 100,000 population)

*In Korea, annually in average, 230 patients/100,000 population visit clinic or hospital due to any causes

**HF patients (≥ 80 YO) visit hospital 14 times frequently compared to general population

National Health Insurance database, 2014, Korea

Background

0.0

0.5

1.0

1.5

2.0

2002 2003 2004 2005 2006 2007 2008 2009 2010

Pre

va

len

ce

(%

)

Year

Men

Women

0.75%

1.06%

1990 2000 2010 2020 2030 2040 2050

Aging is global issue

Trends in aged population according to nation 2012. UN

Prevalence of heart failure by sex in 2002-

2010 (Source : National Health Insurance

Service’s sample cohort database)

0%

10%

20%

30%

40%

USA

Italy

India

China

Japan

Korea

Background

• Average age: 55-65 years vs. 65~70

• Women: 20-25% vs. 50%

• Ischemia etiology (CAD): ≈ 50% vs. ≈ 50%

• Renal insufficiency: usually excluded

(mean Cr 1.1-1.3) vs. 30%

• Preserved LV systolic function: usually excluded (LVEF usually <35-

40) vs. ≈ 50%

• Atrial fibrillation: < 25% vs. >30%

Characteristics of ADHF Patients

Enrolled in Clinical Trials vs. Registry

We need a registry data to evaluate characteristics, clinical profiles

and clinical outcomes of ADHF.


Korean Acute Heart Failure Registries

Korean HF (KorHF)

Registry

Korean Acute HF

(KorAHF) Registry

Study duration 2004. 6 – 2009. 4 2011. 3 – 2014. 2

Sites 24 hospitals 10 hospitals

Patients 3,200 5,600

Sponsor Korean Society

of Cardiology

Korea National

Institute of Health

(KNIH)

F/U duration 1.7 year (0.1-4.9

years) > 3 years, expected

F/U rate 81% 95%

Publications 11 papers 1 design paper

In-hospital

mortality* 6.4% 6.1 %


Eur J Heart Fail. 2014 Jun;16(6):700-8 * : including transplantation

KorAHF ATTEND ADHERE OPTIMIZE-HF EHFSII

Country Korea Japan USA USA Europe

Year 2011.3~2014.2 2007.5-(2012.9) 2001.9-2004.1 2003.3-2004.12 2004.10-2005.8

Sample size 5660 1110 (2009.6) 105388 48612/5791(330) 3580/2981

Follow-up duration >3.0 years 180 days N/A 60,90 days 3-, 12-month

Demographics

Age 68(15) 73 (14) 72 (14) 73 (14) 70 (13)

Male 53.3% 59 48 48 61

Comorbidities

Hypertension 59.2% 71 75 71 63

DM 35.6% 34 44 42 33

Stroke 15.2% 12 17 16 13

AF 27.5% 40 31 31 39

Cause of HF

Ischemia 37% 33 57 60 54

Hypertensive 3.9% 18 N/A 23 11

Summary of baseline data Comparisons of Acute Heart Failure Registry

Eur J Heart Fail. 2014 Jun;16(6):700-8

KorAHF ATTEND ADHERE OPTIMIZE-HF EHFSII

Country Korea Japan USA USA Europe

Year 2011.3~2014.2 2007.5-(2012.9) 2001.9-2004.1 2003.3-2004.12 2004.10-2005.8

Sample size 5660 1110 (2009.6) 105388 48612/5791(330) 3580/2981

Follow-up duration >3.0 years 180 days N/A 60,90 days 3-, 12-month

Clinical status on admission

De novo HF 52.1% 63 24 13 37

Creatinine 1.48 (1.46) 1.4 (1.5) 1.8 (1.6) 1.8 (1.8) N/A

Heart rate 92.7 (27.1) 99 (30) N/A 87 (22) median 95

Systolci BP 131.1 (30.3) 147 (38) 144 (33) 143 (33) median 135

LVEF ≤40% 51.7% 57 47 48.8 46

Management

IV diuretics 74.9% 80 87 N/A 84

IV inotropes 31.3% 21 8 7 <29.8

IV vasodilators 41.0% 46 7 14 38

Outcome

Length of stay (median) 9.0 days 21 4.3 6.4 (mean) 9

in-hospital mortality 4.8% 7.7 3.8 3.8 6.7


Summary of baseline data Comparisons of Acute Heart Failure Registry

Total In-hospital mortality 4.76%

in-hospital mortality: 6.14% Urgent heart transplantation 1.38%

Hospital stay (median) 9 days

Medical cost 9,164,200 Korean won ( 7,968 US $)

Outcomes

After discharge,

90-day mortality: 4.2%

HF readmission rate: 12.9%

ADHERE


Circ Heart Fail. 2011 : from the Biomarkers in Acute Heart Failure (BACH)

Risk factors for in-hospital death

ADHERE, JAMA 2005 OPTIMIZE HF , JAMA 2006

LESS THAN GREATER THAN

2.68%

n=25,122

8.98%

n=7202

SYS BP 115

n=24,933

SYS BP 115

n=7150

6.41%

n=5102

15.28%

n=2048

2.14%

n=20,834

5.49%

n=4099

Cr 2.75

2045

12.42%

n=1425

21.94%

n=620

BUN 43

n=33,324

Highest to Lowest Risk Cohort

OR 12.9 (95% CI 10.4-15.9)

2.6

5.5

7.5

16.3

0

2

4

6

8

10

12

14

16

18

SBP > 100mm HgSCr < 2.0 mg/dL

(n=34,909)

SBP > 100mm Hg SCr ≥ 2.0 mg/dL

(n=9780)

SBP ≤100mm Hg SCr < 2.0 mg/dL

(n=2680)

SBP ≤100mm Hg SCr ≥ 2.0 mg/dL

(n=1243)

In-H

ospita

l M

ort

alit

y (

%)


Predictors of in-hospital mortality Multivariate analysis from KorHF KorAHF registry

Variables Adjusted OR(95% CI) p-value

Lung congestion 1.67 (1.06,2.64) 0.0274

Chronic renal disease in past medical Hx 2.01 (1.34,3.02) 0.0008

Newly detected DM at admission 2.23 (1.15,4.32) 0.0177

Newly detected renal failure

at admission (Cr > 2.0) 4.57 (3.02,6.92) <.0001

Q wave (ECG) 1.97 (1.35,2.87) 0.0005

RBBB (ECG) 1.95 (1.26,3.04) 0.0030

*Other aggravating factors 2.22 (1.44,3.43) 0.0003

BMI < 25kg/m2 2.09 (1.37,3.19) 0.0006

SBP < 100 mmHg 3.41 (2.41,4.82) <.0001

WBC ≥ 10,000 1.80 (1.30,2.50) 0.0004

Sodium < 135 mmEq/L 1.98 (1.42,2.74) <.0001

LVEF < 40% 1.82 (1.29,2.57) 0.0006

C-statistics 0.806

Variables Adjusted OR (95% CI) p-value

Lung congestion 2.38 (1.17,4.82) 0.016

SBP < 100 mmHg 4.45 (2.69,7.37) <0.001

ECG (Q wave) 1.98 (1.07,3.65) 0.029

ECG (RBBB) 2.68 (1.47,4.89) 0.001

Lab (WBC ≥10000/mm3) 1.82 (1.12,2.96) 0.016

Lab (Sodium <135mmol/L) 2.06 (1.27,3.34) 0.003

Lab (Cr ≥2.0mg/dL) 2.83 (1.66,4.81) <0.001

LVEF <40% 1.88 (1.14,3.1) 0.014

Aggravating factor_others 3.17 (1.71,5.86) <0.001

Etiology of heart failure_valvular heart disease 2.12 (1.16,3.89) 0.015

C-statistics 0.807



Eve

nt

fre

e S

urv

iva

l

Hyponatremia Log Rank P < 0.001

NN

HN

OPTIMIZE, HF Gheorghiade M. Eur Heart J 2007

Yoo BS et al. JKIM 2015


in-hopital mortality

in-hopital mortality

Baseline sBP in mortality

Heart 2009 95: 56-62 Yoo BS et al. (submitted to JCF)


Obesity paradox is a global phenomenon

N=6,142 patients from 12 prospective observational cohorts.

Primary outcome: All cause death.

Shah R et al. J Am Coll Cardiol. 2014;63:778-85.

Forest Plot of HR for Association of BMI With All-Cause Mortality All-Cause Mortality 30 Days and 1 Year


Obesity paradox in KorAHF ;

similar result

Unpublished data from KorAHF

Adjusted for several factors


Shah R et al. J Am Coll Cardiol. 2014;63:778-85.

KorAHF Great network

Quality of Care

Fonarow GC et al. Arch Intern Med 2005;165:1469-1477 Yoo BS, Oh JW, Kang SM, Choi DJ, PLoS ONE : 2014

Youn YJ, Yoo BS, Circ J. 2012 Apr 25;76(5):1151-1158 5.0

6.1

3.1

1.4

0.0

2.0

4.0

6.0

8.0

10.0

Length of Stay(median)

Mortality

All P<0.0001

Lagging Centers Leading Centers


Drug adherence in systolic HF

67.6

41.1

58.8

65.7

49.5 44.7

84 83

21

0

10

20

30

40

50

60

70

80

90

100

ACEI/ARB BB AA

KorHF

KorAHF

ADHERE

(%)


Limitation

• Potential biases of registry data

- Selection bias

- Not consecutive patients

- Different socioeconomic status and health

care system

Summary : What’s difference?

1. Background :

– rapidly increasing prevalence of HF (esp. aging)

2. Compared with other registries

– relatively young (mean 69 years old)

– high rate of de novo HF: 52.1%

– low incidence of hypertension and CAD

– low BP at admission

3. Outcomes

– in-hospital mortality (≈5%) with low 90-day mortality rate

– Similar effect of Cr, SBP, BMI and serum sodium level

– low Use of BB at discharge.

Thanks to

• KorAHF Registry Investigator

(PI: BS Oh, and investigators)

• Korea Heart Failure Society Members

(Present: MC Cho and members)

• ACC and KSC

15 (Fri) ~ 16 (Sat) April, 2016 Daegu, Korea

Healthcare

Differences in clinical characteristics and its effect for outcomes