Download Cardiorespiratory Function of Pediatric Heart Transplant Recipients

Authors:
Hsin-Hui Chiu, MD
Mei-Hwan Wu, MD, PhD
Shoei-Shen Wang, MD, PhD
Ching Lan, MD
Nai-Kuan Chou, MD, PhD
Ssu-Yuan Chen, MD, PhD
Jin-Shin Lai, MD
Cardiopulmonary
BRIEF REPORT
Affiliations:
From the Department of Pediatrics,
National Taiwan University Hospital and
National Taiwan University College of
Medicine, Taipei (H-HC, M-HW);
Department of Pediatrics, National
Taiwan University Hospital Yun-Lin
Branch, Yun-Lin (H-HC); Department of
Surgery, National Taiwan University
Hospital and National Taiwan University
College of Medicine, Taipei (S-SW,
N-KC); and Department of Physical
Medicine and Rehabilitation, National
Taiwan University Hospital and National
Taiwan University College of Medicine,
Taipei, Taiwan (CL, S-YC, J-SL).
Cardiorespiratory Function of
Pediatric Heart Transplant Recipients
in the Early Postoperative Period
ABSTRACT
Chiu H-H, Wu M-H, Wang S-S, Lan C, Chou N-K, Chen S-Y, Lai J-S:
Cardiorespiratory function of pediatric heart transplant recipients in the early
postoperative period. Am J Phys Med Rehabil 2012;91:156Y161.
Correspondence:
All correspondence and requests for
reprints should be addressed to:
Ssu-Yuan Chen, MD, PhD, Department
of Physical Medicine and Rehabilitation,
National Taiwan University Hospital,
7 Chun-Shan South Road, Taipei 10002,
Taiwan.
Disclosures:
Financial disclosure statements have
been obtained, and no conflicts of
interest have been reported by the
authors or by any individuals in control
of the content of this article.
0894-9115/11/9102-0156/0
American Journal of Physical
Medicine & Rehabilitation
Copyright * 2012 by Lippincott
Williams & Wilkins
In this study, we sought to assess the cardiopulmonary functions in three pediatric
heart transplant recipients, two of whom are with dilated cardiomyopathy, whereas
one is with cyanotic heart disease, in early postoperative period. Cardiopulmonary
exercise testing was performed using an incremental cycling at 1 mo after surgery.
The results revealed that our study subjects had obvious impairment in workload,
oxygen consumption, and oxygen pulse at peak exercise and ventilatory threshold at
1 mo after orthotropic heart transplantation. The pediatric orthotropic heart transplantation recipients also showed a high resting heart rate (90Y106 beats/min), a
low peak heart rate (109Y117 beats/min) during exercise, and continuous heart
rate acceleration till 1 to 3 mins after the cessation of exercise. In conclusion, pediatric orthotropic heart transplant recipients have a low cardiopulmonary endurance
during the early postoperative period. An early structured, individualized cardiopulmonary rehabilitation program for pediatric orthotropic heart transplant recipients
will be an area for future evaluation and research.
Key Words: Exercise Testing, Oxygen Consumption, Aerobic Capacity, Ventilatory
Threshold, Pediatric Heart Transplantation
DOI: 10.1097/PHM.0b013e318238a0b1
H
eart transplantation is a viable alternative for intractable heart failure and
increases the survival rate significantly. Sustained suboptimal exercise capacity
(50%Y70% of normal values) after transplantation was reported in previous studies; however, physical training may improve exercise capacity.1Y4 Although many
investigations of the cardiorespiratory function after heart transplantations were
reported in adult recipients, the data are scarce in pediatric heart transplant
recipients.5Y9 Heart rate (HR), blood pressure (BP), workload, breath-by-breath
measures of oxygen consumption (V̇O2), carbon dioxide production (V̇CO2), and
minute ventilation (V̇E) during cardiopulmonary exercise testing (CPET) provide
critical information on the exercise capacity of patients with cardiovascular and
pulmonary disease.10 The ventilatory threshold (VeT), assessed using ventilatory
156
Am. J. Phys. Med. Rehabil. & Vol. 91, No. 2, February 2012
Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
expired gas, is a widely used index to evaluate an
individual’s submaximal endurance exercise capacity.10 To our knowledge, no study has reported on
cardiorespiratory responses during CPET in children
who underwent orthotropic heart transplantation
(OHT) in the early postoperative period. In this study,
we report the cardiorespiratory responses to exercise
in three pediatric OHT recipients at 1 mo (28Y35
days) after transplantation.
METHODS
Patients
Case 1
An 11.2-yr-old girl with a case of complete
atrioventricular block underwent permanent pacemaker implantation at the age of 2.8 yrs. Chronic
cardiac dyssynchrony induced dilated cardiomyopathy, and OHT was performed when the girl was
11.2 yrs old.
Case 2
A 13.7-yr-old boy with a history of growth hormone deficiency and hypogammaglobulinemia was
receiving regular growth hormone and immunoglobulin therapy. However, dilated cardiomyopathy
with congestive heart failure occurred at the age of
13 yrs. He had undergone OHT at 13.6 yrs old.
Case 3
A 15.5-yr-old boy had complex heart disease
(double inlet of left ventricle and L-transposition of
great arteries) and received a left Blalock-Taussig
shunt (a palliative graft from subclavian artery to
the pulmonary artery) at the age of 13 yrs. However,
progressive congestive heart failure and arrhythmia developed afterward, and OHT was performed
at 15.4 yrs old.
All three recipients were under tripleimmunosuppressant therapy with tacrolimus, mycophenolate, and prednisolone. The CPET was performed
at 1 mo (28Y35 days) after OHT.
analyzed breath-by-breath using an automatic gas
analyzer (Quark b2 system, Cosmed s.r.l., Rome,
Italy). Exercise cardiopulmonary parameters, including workload, V̇E, V̇O2, V̇CO2, oxygen pulse (O2 pulse),
ventilatory equivalent for oxygen (V̇E/V̇O2), and ventilatory equivalent for carbon dioxide (V̇E/V̇CO2),
were processed.
Exercise Protocol
CPET was performed at least 2 hrs after breakfast. The test began with 2 mins of baseline data
collection while sitting on the cycle ergometer, followed by 2 mins of warm-up cycling with no resistance, then with load increased in a ramp protocol.
The increment of workload was chosen according
to patient’s body weight: increased by 5 W/min for
children weighing under 40 kg, and increased by
10 W/min for those weighing more than 40 kg.
Patients exercised in an upright position until the
appearance of symptoms (i.e., fatigue, angina, undue
dyspnea, claudication, and cerebral symptoms) or
signs (2-mm ST depression over resting electrocardiogram, significant ectopic activity, inappropriate
BP response). In the recovery phase, HR was monitored for 10 mins through unloaded cycling.
The VeT was determined by at least two of the
following criteria: (1) the V̇E/V̇O2 began to increase
systematically without a corresponding increase in
the V̇E/V̇CO2,11 (2) the partial pressure of end tidal
oxygen began to increase without a decrease in the
partial pressure of end tidal carbon dioxide,12 and
(3) departure from linearity for minute ventilation.13
Two independent observers with experience in CPET
determined the VeT. In addition, we performed a
systematic literature search of MEDLINE concerning
exercise capacity in pediatric heart transplantation
recipients and also searched the reference lists of all
identified relevant publications. The study was approved by the research ethics committee of
the hospital, and the guardian of each study subject
signed the informed consent form.
Equipment and Measurement
The CPET was performed on a cycle ergometer
(Corival; Lode BV, Zernikepark 16, Groningen, the
Netherlands) in an air-conditioned laboratory at a
temperature of 22-C to 26-C, barometric pressure
of 756 to 772 mm Hg, and a relative humidity of
54% to 68%. The blood pressure (TANGO; SunTech
Medical Instruments Inc, North Carolina) and continuous 12-lead electrocardiogram (CENTRA Stress
System; Marquette Electronics Inc, Wisconsin) were
monitored during exercise. The expired air was
www.ajpmr.com
RESULTS
Patient Characteristics
The baseline characteristics of the patients
were summarized in Table 1. The resting HR, systolic and diastolic BP, and left ventricular ejection
fraction by echocardiography were measured. None
of the recipients experienced chest pain, dizziness,
or ST depression Q3 mm during exercise.
Pediatric Heart Transplantation
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157
TABLE 1 Characteristics at time of exercise testing
Age, yrs
Sex
Height, cm
Weight, kg
Resting HR, beats/min
Resting SBP, mm Hg
Resting DBP, mm Hg
LVEF, %
1
2
3
11.2
Female
143
32.3
106
117
84
69
13.7
Male
148.5
59.0
101
102
68
76
15.5
Male
161.5
42.5
90
124
71
70
HR, heart rate; SBP, systolic blood pressure; DBP, diastolic
blood pressure; LVEF, left ventricular ejection fraction.
Exercise Performance
The cardiorespiratory responses during exercise were summarized in Table 2. At 1 mo after
OHT, the HR (104Y114 beats/min), workload
(35Y50 W), V̇O2 (12.27Y17.66 ml/kg per minute), O2
pulse (5.0Y7.4 ml/beat), and V̇E (30.1Y36.6 l/min) at
peak exercise were reduced in comparison with
the data of normal children and pediatric OHT recipients in the literature review (Table 3).5Y9,14,15
After cessation of exercise, the HR continued to
accelerate for 1 to 3 mins, reached the maximal HR
(109Y118 beats/min), and then decelerated slowly.
The V̇E/V̇O2 (46Y53) and V̇E/V̇CO2 (35Y48) were higher
than data in Table 3.7
At the VeT, patient’s HR (92Y107 beats/min),
workload (15Y20 W), V̇O2 (9.42Y11.73 ml/kg per
minute), O2 pulse (3.5Y5.4 ml/beat), and V̇E
(16.4Y24.4 L/min) were also lower than that of
previous reports.9
DISCUSSION
CPET measures a broad range of parameters
to evaluate the cardiorespiratory responses to exercise quantitatively and provides a more precise
determination of aerobic capacity.10 V̇E is the volume of air moved into or out of the lungs in 1 min.
The reference range of V̇E varies and increases with
age increment in children and adolescents.15 The
V̇E/V̇O2 reflects the ventilatory requirement for any
oxygen uptake, and it is an index of ventilatory efficiency. The V̇E/V̇CO2 represents the ventilatory requirement to eliminate a given amount of CO2
produced by the metabolizing tissue.16 Lower V̇E
and higher V̇E/V̇O2 and V̇E/V̇CO2 levels were noted in
OHT recipients and patients with congestive heart
failure.7,16Y18 Our study also revealed similar findings (Tables 2 and 3). Greater lactic acidosis or compensation for increased dead space during exercise
might explain the phenomenon.7 The VeT, obtained
during CPET, is closely related to lactate threshold.10
VeT defines the upper range of sustainable exercise
intensity and is considered an indicator of cardiovascular fitness.19 The low V̇O2 at VeT in the current
study, as well as previous reports among adult OHT
recipients, implies poor endurance in participation
in moderate-intensity physical activities.16,20
TABLE 2 Cardiopulmonary responses of the subjects at peak exercise and ventilatory threshold at one
month after heart transplantation
Peak exercise
Workload, W
Peak heart rate, beats/min
Maximal heart rate, beats/min
Systolic BP, mm Hg
Diastolic BP, mm Hg
V̇O2, ml/kg per minute
O2 pulse, ml/beat
V̇E, l/min
V̇E/V̇O2
V̇E/V̇CO2
Ventilatory threshold
Heart rate, beats/min
Workload, W
V̇O2, ml/kg per minute
O2 pulse, ml/beat
V̇E, l/min
V̇e/V̇o2
V̇e/V̇co2
1
2
3
35
114
117
156
77
17.66 (43% of predicted
normal value)
5.0
30.1
53
48
35
114
118
138
96
12.27 (25% of predicted
normal value)
6.5
36.6
46
44
50
104
109
180
82
17.52 (36% of predicted
normal value)
7.4
36.5
46
35
107
15
11.73
3.5
16.4
39
43
104
15
9.43
5.3
24.4
40
40
92
20
11.53
5.4
20.2
37
36
BP, blood pressure; V̇O2, oxygen consumption; V̇E, minute ventilation; V̇E/V̇O2, ventilatory equivalent for oxygen; V̇E/V̇CO2,
ventilatory equivalent for carbon dioxide; W, Watts.
158
Chiu et al.
Am. J. Phys. Med. Rehabil. & Vol. 91, No. 2, February 2012
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14
9.4 T 0.8
3.6 T 0.5
Treadmill
105 T 41
169 T 5
33 T 2.1
Y
Y
Y
Y
Y
16
13 (8Y19)
1.6 (0.5Y5.5)
Bicycle
Y
134 (103Y177)
22.3 (15.9Y35.8)
Y
51.0 (26.1Y87.6)
52.2 (36.2Y63.9)
39.3 (33.9Y47.6)
Y
31
11.7 T 4.1
1.3 T 0.8
Bicycle
68 (10T120)
136 T 22
20 T 6
Y
Y
Y
Y
Y
OHT recipients
24
9.7 T 2.3
9.5 T 2.33
Treadmill
Y
158 T 15
32.3 T 5.6
5.5 T 1.1/m2
Y
Y
Y
27.6 T 9.6
41
13 (7Y18)
Y
Bicycle
140 (70Y300)
194 (167Y214)
41.3 (25.6Y61.4)
Y
72.9 (46.8Y138.8)
37.1 (30.5Y49.8)
33.0 (26.6Y44.0)
Y
25
10.5 T 1.4
Y
Treadmill
Y
189 T 12
36.8 T 5.5
6.1 T 1.7/m2
Y
Y
Y
32.9 T 6.0
170
10Y16
Y
Treadmill
Y
198Y203
51.67Y54.85
Y
62.9Y132.7a
Y
Y
Y
66
13.8 T 2.9
Y
Bicycle
Y
170 T 18
35.5 T 7.4
10.4 T 3.6
Y
Y
34.0 T 6.5
Y
No. subjects
Age, yrs
Time after OHT, yrs
Exercise mode
Workload, W
Peak HR, beats/min
Peak V̇O2 ml/kg per minute
Peak O2 pulse, ml/beat
Peak V̇E, l/min
Peak V̇E/V̇o2
Peak V̇E/V̇co2
V̇O2 at VeT, ml/kg per minute
Normal
HR, heart rate; V̇O2, oxygen consumption; V̇E, minute ventilation; V̇E/V̇O2, ventilatory equivalent for oxygen; V̇E/V̇CO2, ventilatory equivalent for carbon dioxide; VeT, ventilatory threshold; OHT, orthotropic heart transplantation.
28
13.8 T 5.0
2.8 T 0.4
Bicycle/treadmill
62 T 38
152.1 T 15.3
25.0 T 6.7
Y
Y
Y
Y
Y
Davis et al5
Pastore et al8
Nixon et al17
Hsu et al6
Abarbanell et al19
Nixon et al7
Abarbanell et al19
Fredriksen et al15
Yetman et al14
TABLE 3 Reports of cardiopulmonary responses to exercise in normal and pediatric OHT recipients
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In healthy subjects, peak HR during exercise is
mediated by sinus node function and cardiac sympathetic innervation.10,21Y23 After cessation of exercise,
HR recovery is mediated initially by vagal inhibition,
followed by a combination of vagal inhibition and
sympathetic withdraw.21Y23 In the transplanted heart,
sympathetic denervation and lack of local catecholamine release reduces the chronotropic response at
the peak exercise.23 HR recovery after cessation of
exercise is dependent on the removal of circulating
catecholamine and the lack of vagal inhibition, which
leads to continuous HR increment in the first 2 mins
after exercise termination.16,18,23 In addition, a higher
resting HR after OHT has been reported, which may be
attributed to the intrinsic rate of the sinoatrial
node.16,18,23
In this study, our patients displayed a high
resting HR, a low peak HR during exercise, and
continuous HR increase toward 1 to 3 mins after
cessation of exercise in the early postoperative period. These findings were similar with the HR response of adult OHT recipients in our previous
study.16 However, Singh et al.24 indicated that pediatric recipients had a continuous HR deceleration
after cessation of exercise with an attenuated rate at
1 yr after OHT.24 Late autonomic reinnervation of
the transplanted heart during follow-up might explain the attenuation of characteristic HR responses
in OHT recipients.24
Both in adult and pediatric OHT recipients,
sustained suboptimal exercise capacity (50%Y70%
of reference values) is noted.1Y9 Workload, V̇O2, O2
pulse, V̇E at peak exercise, and VeT are significantly
lower in OHT groups.1Y9 These may be attributed
to many factors, including cardiac denervation, graft
rejection, deconditioning, or immunosuppressive
therapy.1Y4 In the current study, the peak V̇O2 of pediatric recipients was 12.3-17.7 ml/kg per minute,
and it was higher than adult recipients at 1 mo after
OHT (9.2 ml/kg per minute).4 This may be attributed to higher metabolic rate in children, muscle
deconditioning, and decreased ventricular function
in adults.4,25
Previous studies reported that higher resting
systolic and diastolic BP and lower peak systolic
BP during cycling were noted in adult OHT recipients.20,25 Many factors are proposed, including
cardiac denervation, chronic elevation of circulating
catecholamine, the adverse effects of immunosuppressants, and reduced vascular compliance caused
by preoperative congestive heart failure.25,26 However, Pastore et al.8 observed similar systolic BP in
resting and peak exercise among healthy children
and OHT groups. In our study, a higher diastolic BP
Pediatric Heart Transplantation
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159
(71Y84 mm Hg) at rest and a lower peak systolic
BP (138Y180 mm Hg) during exercise were noted,8
which was consistent with Chen’s16 data for adult
patients.16
This study was limited to a small sample size.
The cardiorespiratory function of pediatric OHT
recipients has been rarely reported in the literature because of a small sample size and lack of a
standardized training program. Small body size, a
shorter attention span, and lower motivation are
common in children, which makes the CPET more
difficult.24,27 This study simply reported the isolated
results. Many factors such as previous disability and
severity of postoperative course might influence the
results independently of the transplant per se. Continuous patient recruitment is required for further
evaluation. In addition, blood lactate measurement
during CPET was not performed to detect lactate
threshold in this study. We determined VeT as
a reflection of anaerobic threshold in our study
subjects. Although no universal agreement exists
regarding the methods of VeT detection, the confidence of VeT determination in this study was
assured by application of the most common VeT
criteria and calculation from two independent experienced observers.10
In conclusion, this is the first study investigating the cardiorespiratory response of pediatric
OHT patients during exercise in the early postoperative phase. The major findings of this study
can be listed as the following: (1) cardiorespiratory
responses to exercise in pediatric OHT recipients
are similar to adult recipients; (2) pediatric OHT
recipients have obvious impairments in workload,
V̇O2, O2 pulse, and V̇E at the peak exercise and the
VeT. This study provides references for designing
the early cardiac rehabilitation program to enhance
the physical capacity of pediatric OHT recipients. For
example, the VeT detected in CPET might be used
as the individualized training intensity for exercise
prescription for OHT recipients.19 Pediatric OHT recipients with low cardiovascular fitness might have
low levels of physical activity and run the risk of becoming overweight during follow-up.28 An early
structured, individualized cardiopulmonary rehabilitation program for pediatric OHT patients will be an
area for future evaluation and research.
1. Ulubay G, Ulasli SS, Sezgin A, et al: Assessing exercise performance after heart transplantation. Clin
Transplant 2007;21:398Y404
2. Kobashigawa JA, Leaf DA, Lee N, et al: A controlled
Chiu et al.
3. Bernardi L, Radaelli A, Passino C, et al: Effects of
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4. Bartels MN, Whiteson JH, Alba AS, et al: Cardiopulmonary rehabilitation and cancer rehabilitation.
1. Cardiac rehabilitation review. Arch Phys Med
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5. Davis JA, McBride MG, Chrisant MR, et al: Longitudinal assessment of cardiovascular exercise performance after pediatric heart transplantation. J Heart
Lung Transplant 2006;25:626Y33
6. Hsu DT, Garofano RP, Douglas JM, et al: Exercise
performance after pediatric heart transplantation.
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7. Nixon PA, Fricker FJ, Noyes BE, et al: Exercise testing in pediatric heart, heart-lung, and lung transplant
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9. Abarbanell G, Mulla N, Chinnock R, et al: Exercise
assessment in infants after cardiac transplantation.
J Heart Lung Transplant 2004;23:1334Y8
10. Balady GJ, Arena R, Sietsema K et al: Clinician’s
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middle-aged men. J Appl Physiol 1979;46:1039Y46
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