Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website http://www.cardiologyres.org

Original Article

Volume 10, Number 3, June 2019, pages 157-164

Age-Dependent Impact of Pre-Transplant Intensive Care Unit Stay on Mortality in Heart Transplant Recipients

Figure 1. Age group-specific hazard ratios associated with pre-transplant intensive care unit stay for 1-year mortality, with 95% confidence intervals.

Figure 2. Age group-specific hazard ratios associated with pre-transplant intensive care unit stay for overall mortality, with 95% confidence intervals.

**Table 1.** Patient Characteristics According to Pre-Transplant ICU Stay (N = 19,508)
Characteristic	Missing data	Not in ICU (N = 13,199)	In ICU (N = 6,309)	P value
Age group (years)	0			< 0.001
< 1		384 (3%)	841 (13%)
2 - 11		559 (4%)	408 (6%)
12 - 18		520 (4%)	349 (6%)
19 - 29		746 (6%)	434 (7%)
30 - 39		988 (7%)	429 (7%)
40 - 49		1,865 (14%)	765 (12%)
50 - 59		3,792 (29%)	1,468 (23%)
60 - 69		3,996 (30%)	1,468 (23%)
≥ 70		349 (3%)	147 (2%)
Female gender	0	3,573 (27%)	1,944 (31%)	< 0.001
Race	0			< 0.001
Non-Hispanic White		8,928 (68%)	4,028 (64%)
Non-Hispanic Black		2,597 (20%)	1,278 (20%)
Hispanic		1,105 (8%)	677 (11%)
Other		569 (4%)	326 (5%)
Body mass index category	13			< 0.001
Underweight		508 (4%)	521 (8%)
Normal weight		4,526 (34%)	2,716 (43%)
Overweight		8,160 (62%)	3,064 (49%)
Indication for transplant	0			< 0.001
Congenital heart disease		932 (7%)	870 (14%)
Hypertrophic cardiomyopathy		298 (2%)	146 (2%)
Ischemic cardiomyopathy		4,767 (36%)	1,759 (28%)
Non-ischemic cardiomyopathy		6,198 (47%)	3,065 (49%)
Restrictive cardiomyopathy		432 (3%)	207 (3%)
Valvular heart disease		190 (1%)	113 (2%)
Other		382 (3%)	149 (2%)
Mechanical ventilation	0	91 (1%)	758 (12%)	< 0.001
Mechanical circulatory support	0			< 0.001
None		7,790 (59%)	4,778 (76%)
Extracorporeal membrane oxygenation		31 (0.2%)	261 (4%)
Ventricular assist device		5,378 (41%)	1,270 (20%)
Inotrope use	0	3,801 (29%)	4,183 (66%)	< 0.001
Dialysis on waitlist	177	162 (1%)	214 (3%)	< 0.001
Bilirubin > 2 mg/dL	344	985 (8%)	891 (14%)	< 0.001
Infection requiring intravenous antibiotics	486	1,140 (9%)	1,106 (18%)	< 0.001
Allograft ischemia time (h)	340			0.001
< 2		1,533 (12%)	625 (10%)
2 - 4		8,513 (66%)	4,102 (66%)
> 4		2,932 (23%)	1,463 (24%)

Table 1. Patient Characteristics According to Pre-Transplant ICU Stay (N = 19,508)

Characteristic

Missing data

Not in ICU (N = 13,199)

In ICU (N = 6,309)

P value

N (%)

Age group (years)

< 0.001

< 1

384 (3%)

841 (13%)

2 - 11

559 (4%)

408 (6%)

12 - 18

520 (4%)

349 (6%)

19 - 29

746 (6%)

434 (7%)

30 - 39

988 (7%)

429 (7%)

40 - 49

1,865 (14%)

765 (12%)

50 - 59

3,792 (29%)

1,468 (23%)

60 - 69

3,996 (30%)

1,468 (23%)

≥ 70

349 (3%)

147 (2%)

Female gender

3,573 (27%)

1,944 (31%)

< 0.001

Race

< 0.001

Non-Hispanic White

8,928 (68%)

4,028 (64%)

Non-Hispanic Black

2,597 (20%)

1,278 (20%)

Hispanic

1,105 (8%)

677 (11%)

Other

569 (4%)

326 (5%)

Body mass index category

< 0.001

Underweight

508 (4%)

521 (8%)

Normal weight

4,526 (34%)

2,716 (43%)

Overweight

8,160 (62%)

3,064 (49%)

Indication for transplant

< 0.001

Congenital heart disease

932 (7%)

870 (14%)

Hypertrophic cardiomyopathy

298 (2%)

146 (2%)

Ischemic cardiomyopathy

4,767 (36%)

1,759 (28%)

Non-ischemic cardiomyopathy

6,198 (47%)

3,065 (49%)

Restrictive cardiomyopathy

432 (3%)

207 (3%)

Valvular heart disease

190 (1%)

113 (2%)

Other

382 (3%)

149 (2%)

Mechanical ventilation

91 (1%)

758 (12%)

< 0.001

Mechanical circulatory support

< 0.001

None

7,790 (59%)

4,778 (76%)

Extracorporeal membrane oxygenation

31 (0.2%)

261 (4%)

Ventricular assist device

5,378 (41%)

1,270 (20%)

Inotrope use

3,801 (29%)

4,183 (66%)

< 0.001

Dialysis on waitlist

177

162 (1%)

214 (3%)

< 0.001

Bilirubin > 2 mg/dL

344

985 (8%)

891 (14%)

< 0.001

Infection requiring intravenous antibiotics

486

1,140 (9%)

1,106 (18%)

< 0.001

Allograft ischemia time (h)

340

0.001

< 2

1,533 (12%)

625 (10%)

2 - 4

8,513 (66%)

4,102 (66%)

> 4

2,932 (23%)

1,463 (24%)

**Table 2.** Multivariable Cox Proportional Hazards Analysis of 1-Year Mortality After Heart Transplantation (N = 18,396)
Covariate	HR	95% CI	P value
^aHazard ratio (HR) reflects estimate for ages 40 - 49 years. The interaction terms estimate how this HR is modified in other age groups. BMI: body mass index.
Pre-transplant ICU stay^a	1.5	1.2, 2.0	0.003
Age group (years)
< 1	0.8	0.5, 1.3	0.434
2 - 11	0.5	0.3, 0.8	0.002
12 - 18	0.4	0.3, 0.7	0.001
19 - 29	0.9	0.7, 1.3	0.685
30 - 39	1.2	0.9, 1.6	0.153
40 - 49	Ref.	-	-
50 - 59	1.3	1.0, 1.6	0.025
60 - 69	1.8	1.5, 2.2	< 0.001
≥ 70	2.1	1.5, 3.0	< 0.001
Interaction of ICU stay with age group (years)
< 1	0.7	0.4, 1.1	0.139
2 - 11	0.6	0.3, 1.1	0.110
12 - 18	0.8	0.4, 1.6	0.536
19 - 29	0.8	0.5, 1.4	0.472
30 - 39	0.8	0.5, 1.2	0.276
40 - 49	Ref.	-	-
50 - 59	0.9	0.6, 1.3	0.536
60 - 69	0.7	0.5, 1.0	0.067
≥ 70	0.6	0.3, 1.2	0.171
Female gender	1.1	1.0, 1.3	0.025
Race
Non-Hispanic White	Ref.	-	-
Non-Hispanic Black	1.4	1.2, 1.5	< 0.001
Hispanic	1.1	0.9, 1.3	0.310
Other	1.1	0.8, 1.3	0.657
BMI category
Underweight	0.8	0.7, 1.1	0.163
Normal weight	Ref.	-	-
Overweight	1.1	1.0, 1.3	0.015
Indication for transplant
Congenital heart disease	Ref.	-	-
Hypertrophic cardiomyopathy	0.5	0.3, 0.7	< 0.001
Ischemic cardiomyopathy	0.4	0.4, 0.5	< 0.001
Non-ischemic cardiomyopathy	0.4	0.3, 0.4	< 0.001
Restrictive cardiomyopathy	0.6	0.5, 0.8	< 0.001
Valvular heart disease	0.4	0.2, 0.6	< 0.001
Other	0.3	0.2, 0.5	< 0.001
Mechanical ventilation	1.8	1.5, 2.2	< 0.001
Mechanical circulatory support
None	Ref.	-	-
Extracorporeal membrane oxygenation	3.1	2.4, 4.0	< 0.001
Ventricular assist device	1.4	1.2, 1.6	< 0.001
Inotrope use	1.0	0.9, 1.1	0.567
Dialysis on waitlist	2.2	1.8, 2.8	< 0.001
Bilirubin > 2 mg/dL	1.6	1.4, 1.9	< 0.001
Infection requiring intravenous antibiotics	1.2	1.1, 1.4	0.001
Allograft ischemia time (h)
< 2	Ref.	-	-
2 - 4	1.0	0.8, 1.2	0.878
> 4	1.3	1.1, 1.6	0.001

Table 2. Multivariable Cox Proportional Hazards Analysis of 1-Year Mortality After Heart Transplantation (N = 18,396)

Covariate

95% CI

P value

^aHazard ratio (HR) reflects estimate for ages 40 - 49 years. The interaction terms estimate how this HR is modified in other age groups. BMI: body mass index.

Pre-transplant ICU stay^a

1.5

1.2, 2.0

0.003

Age group (years)

< 1

0.8

0.5, 1.3

0.434

2 - 11

0.5

0.3, 0.8

0.002

12 - 18

0.4

0.3, 0.7

0.001

19 - 29

0.9

0.7, 1.3

0.685

30 - 39

1.2

0.9, 1.6

0.153

40 - 49

Ref.

50 - 59

1.3

1.0, 1.6

0.025

60 - 69

1.8

1.5, 2.2

< 0.001

≥ 70

2.1

1.5, 3.0

< 0.001

Interaction of ICU stay with age group (years)

< 1

0.7

0.4, 1.1

0.139

2 - 11

0.6

0.3, 1.1

0.110

12 - 18

0.8

0.4, 1.6

0.536

19 - 29

0.8

0.5, 1.4

0.472

30 - 39

0.8

0.5, 1.2

0.276

40 - 49

Ref.

50 - 59

0.9

0.6, 1.3

0.536

60 - 69

0.7

0.5, 1.0

0.067

≥ 70

0.6

0.3, 1.2

0.171

Female gender

1.1

1.0, 1.3

0.025

Race

Non-Hispanic White

Ref.

Non-Hispanic Black

1.4

1.2, 1.5

< 0.001

Hispanic

1.1

0.9, 1.3

0.310

Other

1.1

0.8, 1.3

0.657

BMI category

Underweight

0.8

0.7, 1.1

0.163

Normal weight

Ref.

Overweight

1.1

1.0, 1.3

0.015

Indication for transplant

Congenital heart disease

Ref.

Hypertrophic cardiomyopathy

0.5

0.3, 0.7

< 0.001

Ischemic cardiomyopathy

0.4

0.4, 0.5

< 0.001

Non-ischemic cardiomyopathy

0.4

0.3, 0.4

< 0.001

Restrictive cardiomyopathy

0.6

0.5, 0.8

< 0.001

Valvular heart disease

0.4

0.2, 0.6

< 0.001

Other

0.3

0.2, 0.5

< 0.001

Mechanical ventilation

1.8

1.5, 2.2

< 0.001

Mechanical circulatory support

None

Ref.

Extracorporeal membrane oxygenation

3.1

2.4, 4.0

< 0.001

Ventricular assist device

1.4

1.2, 1.6

< 0.001

Inotrope use

1.0

0.9, 1.1

0.567

Dialysis on waitlist

2.2

1.8, 2.8

< 0.001

Bilirubin > 2 mg/dL

1.6

1.4, 1.9

< 0.001

Infection requiring intravenous antibiotics

1.2

1.1, 1.4

0.001

Allograft ischemia time (h)

< 2

Ref.

2 - 4

1.0

0.8, 1.2

0.878

> 4

1.3

1.1, 1.6

0.001

**Table 3.** Multivariable Cox Proportional Hazards Analysis of Overall Mortality After Heart Transplantation (N = 18,396)
Covariate	HR	95% CI	P value
^aHazard ratio (HR) reflects estimate for ages 40 - 49 years. The interaction terms estimate how this HR is modified in other age groups. BMI: body mass index.
Pre-transplant ICU stay^a	1.3	1.1, 1.5	0.007
Age group (years)
< 1	0.8	0.6, 1.0	0.060
2 - 11	0.6	0.5, 0.8	< 0.001
12 - 18	0.9	0.7, 1.2	0.583
19 - 29	1.4	1.2, 1.7	< 0.001
30 - 39	1.1	0.9, 1.3	0.196
40 - 49	Ref.	-	-
50 - 59	1.1	0.9, 1.2	0.342
60 - 69	1.3	1.2, 1.5	< 0.001
≥ 70	1.8	1.4, 2.2	< 0.001
Interaction of ICU stay with age group (years)
< 1	0.9	0.6, 1.3	0.587
2 - 11	0.7	0.5, 1.1	0.115
12 - 18	0.7	0.5, 1.0	0.069
19 - 29	0.9	0.7, 1.2	0.590
30 - 39	0.9	0.7, 1.2	0.396
40 - 49	Ref.	-	-
50 - 59	0.9	0.7, 1.1	0.276
60 - 69	0.9	0.7, 1.1	0.246
≥ 70	0.6	0.4, 1.0	0.051
Female gender	1.1	1.0, 1.2	0.015
Race
Non-Hispanic White	Ref.	-	-
Non-Hispanic Black	1.5	1.4, 1.6	<0.001
Hispanic	1.0	0.9, 1.1	0.956
Other	1.0	0.9, 1.2	0.716
BMI category
Underweight	1.0	0.8, 1.1	0.807
Normal weight	Ref.	-	-
Overweight	1.2	1.1, 1.3	< 0.001
Indication for transplant
Congenital heart disease	Ref.	-	-
Hypertrophic cardiomyopathy	0.5	0.4, 0.7	< 0.001
Ischemic cardiomyopathy	0.8	0.7, 0.9	0.001
Non-ischemic cardiomyopathy	0.6	0.5, 0.7	< 0.001
Restrictive cardiomyopathy	0.8	0.6, 0.9	0.014
Valvular heart disease	0.6	0.4, 0.7	< 0.001
Other	0.6	0.4, 0.7	< 0.001
Mechanical ventilation	1.3	1.1, 1.5	0.002
Mechanical circulatory support
None	Ref.	-	-
Extracorporeal membrane oxygenation	2.0	1.6, 2.5	< 0.001
Ventricular assist device	1.1	1.0, 1.2	0.001
Inotrope use	1.0	0.9, 1.1	0.632
Dialysis on waitlist	1.8	1.5, 2.2	< 0.001
Bilirubin > 2 mg/dL	1.2	1.1, 1.3	< 0.001
Infection requiring IV antibiotics	1.2	1.1, 1.3	< 0.001
Allograft ischemia time (h)
< 2	Ref.	-	-
2 - 4	1.0	0.9, 1.1	0.888
> 4	1.2	1.1, 1.4	< 0.001

Table 3. Multivariable Cox Proportional Hazards Analysis of Overall Mortality After Heart Transplantation (N = 18,396)

Covariate

95% CI

P value

^aHazard ratio (HR) reflects estimate for ages 40 - 49 years. The interaction terms estimate how this HR is modified in other age groups. BMI: body mass index.

Pre-transplant ICU stay^a

1.3

1.1, 1.5

0.007

Age group (years)

< 1

0.8

0.6, 1.0

0.060

2 - 11

0.6

0.5, 0.8

< 0.001

12 - 18

0.9

0.7, 1.2

0.583

19 - 29

1.4

1.2, 1.7

< 0.001

30 - 39

1.1

0.9, 1.3

0.196

40 - 49

Ref.

50 - 59

1.1

0.9, 1.2

0.342

60 - 69

1.3

1.2, 1.5

< 0.001

≥ 70

1.8

1.4, 2.2

< 0.001

Interaction of ICU stay with age group (years)

< 1

0.9

0.6, 1.3

0.587

2 - 11

0.7

0.5, 1.1

0.115

12 - 18

0.7

0.5, 1.0

0.069

19 - 29

0.9

0.7, 1.2

0.590

30 - 39

0.9

0.7, 1.2

0.396

40 - 49

Ref.

50 - 59

0.9

0.7, 1.1

0.276

60 - 69

0.9

0.7, 1.1

0.246

≥ 70

0.6

0.4, 1.0

0.051

Female gender

1.1

1.0, 1.2

0.015

Race

Non-Hispanic White

Ref.

Non-Hispanic Black

1.5

1.4, 1.6

<0.001

Hispanic

1.0

0.9, 1.1

0.956

Other

1.0

0.9, 1.2

0.716

BMI category

Underweight

1.0

0.8, 1.1

0.807

Normal weight

Ref.

Overweight

1.2

1.1, 1.3

< 0.001

Indication for transplant

Congenital heart disease

Ref.

Hypertrophic cardiomyopathy

0.5

0.4, 0.7

< 0.001

Ischemic cardiomyopathy

0.8

0.7, 0.9

0.001

Non-ischemic cardiomyopathy

0.6

0.5, 0.7

< 0.001

Restrictive cardiomyopathy

0.8

0.6, 0.9

0.014

Valvular heart disease

0.6

0.4, 0.7

< 0.001

Other

0.6

0.4, 0.7

< 0.001

Mechanical ventilation

1.3

1.1, 1.5

0.002

Mechanical circulatory support

None

Ref.

Extracorporeal membrane oxygenation

2.0

1.6, 2.5

< 0.001

Ventricular assist device

1.1

1.0, 1.2

0.001

Inotrope use

1.0

0.9, 1.1

0.632

Dialysis on waitlist

1.8

1.5, 2.2

< 0.001

Bilirubin > 2 mg/dL

1.2

1.1, 1.3

< 0.001

Infection requiring IV antibiotics

1.2

1.1, 1.3

< 0.001

Allograft ischemia time (h)

< 2

Ref.

2 - 4

1.0

0.9, 1.1

0.888

> 4

1.2

1.1, 1.4

< 0.001