Pediatr Cardiol DOI 10.1007/s00246-015-1143-3

ORIGINAL ARTICLE

The Effects of Pulmonary Valve Replacement for Severe Pulmonary Regurgitation on Exercise Capacity and Cardiac Function Jason G. Ho1 • Marcus S. Schamberger1 • Roger A. Hurwitz1 • Tiffanie R. Johnson1 Lauren E. Sterrett1 • Eric S. Ebenroth1



Received: 3 December 2014 / Accepted: 4 March 2015 Ó Springer Science+Business Media New York 2015

Abstract Patients may develop hemodynamic abnormalities after right ventricular outflow tract (RVOT) repair. Re-intervention timing remains a dilemma. This study evaluates exercise capacity and RV function before and after intervention using age-related comparisons. Twentysix patients with severe pulmonary regurgitation (PR) after initial repair scheduled for pulmonary valve replacement (PVR) were enrolled. Metabolic treadmill testing (EST) and MRI were obtained before and after surgery. EST results were compared with matched controls. Preoperative exercise time and peak oxygen consumption (VO2 max) were significantly diminished compared with controls but were not significantly different postoperatively. The patients were then split into age-related cohorts. When comparing pre-PVR and post-PVR exercise time and VO2 max among themselves, neither cohort showed significant differences. However, patients younger than 25 years had better postoperative results, an age-related difference not seen in the controls. Preoperative MRI showed significantly dilated RV, PR, and low normal function. After PVR, the right to left ventricular end-diastolic volume ratio (RVEDV:LVEDV) and pulmonary artery regurgitant fraction (RF) significantly decreased. There was no change in ventricular ejection fractions (EF). Severe PR, decreased RVEF, and RV dilation can significantly diminish exercise capacity. PVR improves RVEDV:LVEDV and RF, but not EF. Younger patients had better exercise capacity that was

& Jason G. Ho [email protected] 1

Section of Cardiology, Department of Pediatrics, Riley Hospital for Children at Indiana University Health, Indiana University School of Medicine, 699 Riley Hospital Drive, RR 127, Indianapolis, IN 46202, USA

maintained postoperatively. This age-related difference was not seen in the controls, indicating that earlier intervention may preserve exercise capacity. Serial ESTs in patients with severe PR following RVOT repair may identify deteriorating exercise capacity as an early indicator for the need for PVR. Keywords Pulmonary valve replacement  Tetralogy of Fallot  Exercise capacity

Introduction Multiple congenital heart conditions seen in pediatric cardiology involve malformation of the pulmonary or right ventricular outflow tract (RVOT). Patients with this pathology undergo RVOT repair during initial surgery, usually with patching of their native outflow tract or with placement of a conduit between the right ventricle (RV) and pulmonary artery (PA). Initial RVOT repair by these methods is known to have limited duration. There is a risk of development of pulmonary stenosis (PS) from calcification or unequal growth as well as pulmonary regurgitation (PR) from loss of valvular competency. Severe PR after initial RVOT repair leads to volume overload in the RV, which can lead to chronic issues including decreased exercise performance [2, 22, 32], development of both right and left ventricular dysfunction [3, 4], ventricular arrhythmias [31], and symptoms such as dyspnea, fatigue, syncope, palpitations, nausea, chest pain, and sudden death [1, 6, 12, 13, 19]. Even after developing moderate-to-severe PR, patients may remain asymptomatic. Dependence on clinical evaluation may mislead practitioners as the initial presentation of PR may be subtle. Studies have previously

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evaluated the impact of timing of pulmonary valve replacement (PVR) on the RV, with suggestion of early replacement being beneficial to avoid progressive RV dilatation and dysfunction even with lack of symptomatology [4, 24]. However, drawbacks exist for early valve replacement. The replacement valve used in PVR also has limited durability due to eventual loss of structural stability with time and accelerated rate of patient growth [8, 18]. Accordingly, once a new valve is placed, the time period for subsequent PVR effectively has started, increasing the future surgical burden for the patient. These complicating factors cloud the optimal timing of PVR in this patient population and result in a difficult clinical dilemma. In addition, studies have resulted in conflicting reports on the measured impact of PVR on exercise capacity [5, 7, 10, 11, 21, 23, 27]. Exercise stress testing (EST) has been found to have high sensitivity and specificity in identifying TOF patients with severe PR and RV dysfunction [11]. Thus, evaluation of the exercise capacity and parameters of RV function before and after PVR may help guide clinicians regarding optimal PVR timing. The purpose of this study was to evaluate exercise capacity via standard metabolic treadmill EST and RV function via cardiac magnetic resonance imaging (MRI) before and after PVR for severe PR. The hypothesis is that both exercise capacity and RV hemodynamics would significantly improve after successful PVR.

Methods The Institutional Review Board at Indiana University approved this prospective study. Patients were status postinitial RVOT repair, had developed severe PR, and were already scheduled for PVR by their primary cardiologists. Exclusion criteria included complex congenital heart disease that was unrepaired or non-palliated, moderate-tosevere concomitant PS, inability to undergo metabolic treadmill EST, failure to return for follow-up, and the presence of any other serious conditions that could complicate management and follow-up. Informed consent was obtained from all subjects eligible for enrollment into the study and prior to all testing. The study patients underwent a maximal treadmill EST on a Quinton Q-Stress TM55 treadmill (Quinton Cardiology, Bothell, WA, USA), utilizing the standard Bruce protocol. Metabolic testing was also done during the treadmill test with a Sensormedics Vmax29 metabolic cart (CareFusion, San Diego, CA, USA) using breath-by-breath expired gas collection. A valid maximal oxygen consumption (VO2 max) test was defined when a subject had a respiratory quotient (RQ) of greater than 1.0 and either

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stopped due to volitional exhaustion or achievement of 95 % of the age-predicted maximum heart rate, based on the formula: 208-0.7(age) [17]. Anaerobic threshold (AT) was calculated and defined as the point at which the ventilatory equivalent ratio for oxygen (VE/VO2) increased disproportionately to the ventilatory equivalent ratio for carbon dioxide (VE/VCO2). The AT was then compared with the predicted VO2 max, and the percentile was recorded, with normal being greater or equal to 40 %. Oxygen pulse was measured in milliliters per beat and serves an estimation of stroke volume. In addition, the VE/ VCO2 slope was measured and recorded at peak exercise. EST comparisons between study subjects prior to surgery and healthy controls were also performed. The control subjects were selected from our exercise database of healthy individuals who had completed the maximal treadmill EST. The controls were age- and gender-matched to the study subjects, and when possible, the controls were matched for body mass index (BMI) also. Both the study subjects and healthy controls were also split into age-related cohorts to look at the effects of surgical timing on exercise capacity. Initial statistical analysis using two sample t tests was performed on age cohorts to determine whether a specific age could be identified that would create a significant distinction between younger and older patients. This age could then serve as a possible age time limit for consideration for PVR. As a result, the younger cohort was defined as an age less than 25 years, with the older cohort consisting of individuals greater or equal to 25 years old. Cardiac MRI studies were performed on a 1.5-T clinical scanner (MAGNETOM Avanto, Siemens Medical Solutions, Erlangen, Germany) using a standard imaging protocol including 3D steady-state free precession (SSFP) ECG- and respiratory-gated axial plane images (WHOLE HEART); retrospective ECG-gated, SSFP (TrueFISP) cine images of 4-chamber and entire short axis stack from the base to apex of the heart covering the entire ventricular cavities (for volumetric analysis); and additional TrueFISP cines in appropriate planes to evaluate specific anatomy. Post-processing analyses of function and flow were performed with the use of dedicated software (Argus; Siemens Medical Solutions). Tracing of cavity borders to obtain end-systolic and end-diastolic volumes was used to calculate stroke volumes and ejection fraction for the right and left ventricles. Through-plane phase contrast velocity-encoded imaging was used to determine forward and reverse volume for calculation of regurgitant fraction (RF) in selected vessels. Statistical analysis included paired t tests to compare the preoperative and postoperative EST and MRI data for study subjects; two sample t tests and v2 tests to compare subjects versus controls when appropriate on EST data and

Pediatr Cardiol

subject characteristics; and separate linear regression models to evaluate each change from post-surgery to presurgery EST measurements. In each model, covariates included the pre-surgery value of the EST measurement, surgery characteristics potentially associated with the outcome, and the interaction between the two. Analysis was performed using SAS, version 9.2 (SAS, Cary, NC, USA). Statistical significance for this study was defined as p B 0.05 (two-tailed).

Results Twenty-six patients (15 males, 11 females) were initially enrolled into the study with the following diagnoses: Tetralogy of Fallot (n = 18, including 1 with absent valve and 1 with discontinuous pulmonary arteries), double-outlet RV with ventricular septal defect (VSD) and pulmonary atresia (n = 4), pulmonary atresia with VSD (n = 3), and PS with PR (n = 1). The PS patient had a valvotomy with RVOT patch placement at 18 months and eventually developed severe PR. The patients were repaired initially at the average age of 3.4 ± 3.2 years (range 0.1–16.6) using the following types of repair: transannular patch (n = 19), valvulotomy with transannular patch (n = 3), non-valved RV–PA conduit (n = 3), and valved RV–PA conduit (n = 1). The patients had their most recent PVRs done at an average age of 20.0 ± 7.6 years (10–47.1) with the following replacement types: bovine valve (n = 15), porcine valve (n = 9), and homograft (n = 2). All patients underwent standard metabolic EST an average of 1.2 ± 2.1 months (range 0.0–9.9 months) before their PVR and an average of 14.1 ± 4.3 months (5.6–27.6) after surgery. In addition, 11 patients who had a cardiac MRI performed an average of 6.4 ± 4.6 months (range 1.3–12.4 months) prior to surgery and an average of 14.9 ± 1.8 months (12.5–18.4) after PVR. Individual patient characteristics are listed in Table 1. Preoperative patient EST results were compared with those of the control group as seen in Table 2. The preoperative exercise time, VO2 max, and oxygen pulse were significantly diminished in the patient cohort compared with the controls. In addition, the patients had a significantly blunted heart rate response to maximal exercise compared with controls. Patient Preoperative Versus Postoperative Comparison The exercise test results for the patients before and after PVR were then compared as shown in Table 3. Exercise

time (Fig. 1), VO2 max (Fig. 2), percent predicted VO2 max, percent predicted peak heart rate, oxygen pulse, VE/ VCO2 slope, and anaerobic threshold to VO2 max percentage were all found not to have significant changes after PVR. Magnetic Resonance Imaging Magnetic resonance imaging results for the 11 available patients are listed in Table 3 and illustrated in Fig. 3a–d. Initial preoperative MRI data showed evidence of significantly dilated RVs with marked PR and low normal RV function. After surgery, a comparison of the pre- and postoperative MRI findings showed a significant decrease in the right ventricular to left ventricular end-diastolic volume ratio (RVEDV:LVEDV), pulmonary artery RF, indexed RV end-diastolic volume, and indexed RV endsystolic volume. There was no significant change in either ventricular ejection fraction. Age-Related Comparisons The results were then analyzed by dividing the patient cohort into two age-related groups: \ 25 years (n = 20) and C 25 years (n = 6). The younger and older age cohorts were then compared separately with respect to preoperative and postoperative EST performance. Neither cohort showed a significant difference in comparing preand postoperative exercise times, VO2 max, percent predicted VO2 max, percent predicted peak heart rate, oxygen pulse, VE/VCO2 slope, or anaerobic threshold to VO2 max percentage as shown in Table 4. A comparison was then made between the two age cohorts to look at age-related differences before and after surgery. Prior to surgery, the younger patients had better exercise parameters than the older group (Table 5), but none to a significant degree. After surgery, the younger patients had higher exercise parameters compared with the older cohort with the exception of oxygen pulse. For the younger cohort, the parameters of VO2 max and percent predicted peak heart rate were significantly higher than those of the older cohort. Of note, although the VE/VCO2 slope was significantly higher in the younger cohort compared with the older, both groups had results within normal limits. To create an age-related reference, a similar comparison was performed in the control population that was also split into identical age-related groups defined as those control individuals younger than 25 years and those 25 years and older. No significant age-related difference was seen for any of the measured exercise parameters as seen in Table 6.

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Pediatr Cardiol Table 1 Subject characteristics Subject number

Sex

Diagnoses

1

M

TOF

2

F

3

F

4

Age at initial repair

Age at PVR

Age at EST 1

Age at EST 2

Age at MRI 1

Age at MRI 2

0.9

10.0

10.0

11.4

PA, VSD

3.4

11.5

11.5

12.4

TOF

1.8

13.4

13.2

14.5

M

TOF

1.9

13.5

13.5

14.5

5

M

TOF absent valve

0.6

13.7

13.7

14.8

6

M

TOF

1.5

16.2

13.6

14.8

16.2

17.4

16.1

17.4

7 8

M F

TOF TOF

4.3 2.0

16.5 17.0

16.1 16.7

17.5 17.7

9

M

TOF

2.8

16.7

16.7

17.9

15.7

17.9

10

M

DORV, VSD, PS

0.4

17.3

17.3

18.4

16.6

18.4

11

F

TOF

0.1

17.8

17.6

18.2

12

M

TOF

2.2

16.8

16.8

18.2

15.8

18.2

13

F

DORV, VSD, PA

4.7

18.1

18.1

18.6

14

F

DORV, VSD, PA

5.0

17.2

17.2

18.6

15

M

TOF

1.1

18.4

18.4

19.3

18.2

19.5

16

F

TOF

4.3

18.4

18.3

19.8

18.1

19.7

17

F

DORV, VSD, PA

5.1

18.7

17.9

19.8

17.9

19.8

18

M

TOF

3.9

19.2

19.1

20.5

19

M

TOF

2.5

19.8

19.7

21.3

18.7

21.3

20

M

PS, PI

1.5

23.3

23.2

24.6

23.0

24.7

21

F

TOF

3.0

25.8

25.7

27.5

22 23

F F

PA, VSD TOF

6.9 1.5

25.2 28.9

25.2 28.9

27.5 30.1

28.6

30.1

24

M

PA, VSD

5.9

28.8

28.8

30.1

25

M

TOF

4.0

30.1

30.0

31.2

26

M

TOF

16.6

47.1

46.9

48.2

Ages expressed in years TOF tetralogy of Fallot, PA pulmonary atresia, VSD ventricular septal defect, DORV double-outlet right ventricle, PS pulmonary stenosis, PI pulmonary insufficiency

Table 2 Patient–control comparison of demographics and exercise stress test results

Patients (n = 26)

Controls (n = 26)

Female gender

11 (42.3 %)

11 (42.3 %)

1.00

Age at first EST

19.9 ± 7.6 (10–47)

19.0 ± 7.6 (8–43)

0.68

Height (cm)

165.6 ± 12.5 (128.2–185.4)

169.2 ± 12.1 (131–186.5)

0.30

Weight (kg)

61.7 ± 15.7 (25.4–96.6)

63.2 ± 12.7 (29.5–87.0)

0.70

Body mass index (kg/m2)

22.2 ± 4.3 (15.5–30.8)

21.9 ± 2.5 (17.2–26.0)

0.71

Exercise time (min)

10.7 ± 2.7 (5.0–16.5)

14.5 ± 2.9 (9.9–21.0)

\0.0001

VO2 max (ml/kg/min)

27.8 ± 8.1 (13.4–46.8)

41.2 ± 9.6 (25.7–58.4)

\0.0001

% Predicted peak heart rate

89.0 ± 10.6 (53.7–102.1)

94.1 ± 4.4 (86.7–106.2)

0.029

Oxygen pulse (mL/beat)

9.6 ± 4.1 (3.8–18.4)

14.0 ± 4.9 (7.4–22.4)

0.0024

Values expressed either as n (%) or mean ± standard deviation (range) EST exercise stress testing; VO2 max maximal oxygen consumption

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p value

Pediatr Cardiol Table 3 Paired t test results comparing exercise stress testing and MRI before and after surgery

n

Pre-surgery

Post-surgery

Change from pre-surgery

p value

Exercise stress testing (n = 26) Exercise time (min)

26

10.7 ± 2.7

10.7 ± 2.2

0.020 ± 1.73

0.95

VO2 max (ml/kg/min)

26

27.8 ± 8.1

28.3 ± 7.9

0.48 ± 6.50

0.71

% Predicted VO2 max

26

65.4 ± 18.8

67.2 ± 17.8

1.8 ± 14.8

0.54

% Predicted peak HR

26

89.0 ± 10.6

89.1 ± 12.0

0.13 ± 11.7

0.96 0.48

Oxygen pulse (mL/beat)

20

9.6 ± 4.1

9.9 ± 3.6

0.31 ± 1.9

VE/VCO2 slope

24

33.6 ± 5.3

32.4 ± 3.9

-1.2 ± 4.2

0.17

AT to VO2 max %

22

49.8 ± 12.4

49.6 ± 9.2

-0.18 ± 10.2

0.93

Magnetic resonance imaging (n = 11) RVEDV:LVEDV

11

1.89 ± 0.25

1.20 ± 0.12

-0.7 ± 0.3

\0.0001

MPA RF

11

0.46 ± 0.10

0.01 ± 0.01

-0.45 ± 0.10

\0.0001

RVEF

11

0.47 ± 0.06

0.48 ± 0.09

0.01 ± 0.12

0.88

LVEF

11

0.57 ± 0.07

0.54 ± 0.10

-0.03 ± 0.07

0.16

Indexed RVEDV (ml/m2)

11

133.2 ± 22.0

99.7 ± 24.4

-33.5 ± 22.0

0.0005

Indexed RVESV (ml/m2)

11

70.6 ± 16.8

52.8 ± 18.1

-17.8 ± 18.6

0.01

Values expressed as mean ± standard deviation (range) VO2 max maximal oxygen consumption, HR heart rate, VE/VCO2 ventilatory equivalent ratio for carbon dioxide, AT anaerobic threshold, RVEDV:LVEDV right ventricular to left ventricular end-diastolic volume ratio, MPF RF main pulmonary artery regurgitant fraction, RVEF right ventricular ejection fraction, LVEF left ventricular ejection fraction, RVEDV right ventricular end-diastolic volume, RVESV right ventricular end-systolic volume

50

18

45

16

40

VO2 Max (mL/kg/min)

Exercise Time (min)

14

12

10

8

6

4

35 30 25 20 15

Pre-Op

Post-Op

Fig. 1 Exercise time preoperative versus postoperative. Comparing the individual exercise times for each patient before and after pulmonary valve replacement. The preoperative and postoperative means were 10.7 ± 2.7 and 10.7 ± 2.2 min, respectively (p = ns). Patients 20 and 25 from Table 1 were noted to have decreased postoperatively in exercise time

Discussion Patients with severe PR following RVOT repair can have diminished exercise capacity, decreased RVEF, and RV dilatation. PVR did not significantly improve the exercise capacity of our patients. Intervention with PVR did result

10

Pre-Op

Post-Op

Fig. 2 VO2 max preoperative versus postoperative. Comparing the individual VO2 max for each patient before and after pulmonary valve replacement. The preoperative and postoperative means were 27.8 ± 8.1 and 28.3 ± 7.9 ml/kg/min, respectively (p = ns). Patient 1 from Table 1 had a notable increase in VO2 max postoperatively

in a marked reduction in RV size and PA regurgitant fraction on MRI. Importantly, younger patients tended to have better exercise capacity prior to surgery and maintained that capacity after PVR. This age-related difference in exercise capacity was not seen in the control population, indicating that perhaps earlier intervention in those with severe PR

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a

b

2.5

0.70 0.60

MPA Regurgitant Fraction

RVEDV:LVEDV

2.0

1.5

1.0

0.5

0.50 0.40 0.30 0.20 0.10

0.0

0.00

Post-Op

d 0.70

0.50 0.40 0.30 0.20 0.10 0.00

Pre-Op

Post-Op

Pre-Op

Post-Op

0.80 0.70

0.60

Left Ventricular Ejection Fraction

Right Ventricular Ejection Fraction

c

Pre-Op

Pre-Op

Post-Op

0.60 0.50 0.40 0.30 0.20 0.10 0.00

Fig. 3 Magnetic resonance imaging parameters preoperative versus postoperative. a A comparison of the right ventricular with left ventricular end-diastolic volume ratio before and after pulmonary valve replacement. The preoperative and postoperative means were 1.89 ± 0.25 and 1.20 ± 0.12, respectively (p \ 0.0001). b A comparison of the pulmonary arterial regurgitant fraction before and after pulmonary valve replacement. The preoperative and postoperative means were 0.46 ± 0.10 and 0.01 ± 0.01, respectively (p \ 0.0001). c A comparison of the right ventricular ejection fraction before and

after pulmonary valve replacement. The preoperative and postoperative means were 0.47 ± 0.06 and 0.48 ± 0.09, respectively (p = ns). Patients 5 and 10 from Table 1 had a notable decrease in right ventricular ejection fraction after pulmonary valve replacement. d A comparison of the left ventricular ejection fraction before and after pulmonary valve replacement. The preoperative and postoperative means were 0.57 ± 0.07 and 0.54 ± 0.10, respectively (p = ns)

would allow for better preservation of exercise capacity in this patient population. Intervention with PVR appears to stabilize exercise capacity in our patient cohort in the short- to medium-term postoperative period of approximately 1 year.

that compared with controls, patients had significantly depressed peak VO2 values and abnormal RV response to exercise likely due to long-standing volume overload with an increased RVEDV and lack of decrease in RVESV. This study compared the results of EST for individual subjects before and after PVR at an average age of 20.0 years with no significant difference seen in any EST parameters. Others have also found little to no improvement in exercise capacity and VO2 max after PVR, with average subject ages of 24, 23.8, and 27.9 [7, 10, 27]. Various theories have been proposed as to why no improvement in EST parameters is sometimes seen after

Evaluation for Pulmonary Valve Replacement Using Exercise Stress Testing The results of this study showed a significant decrease in exercise time, VO2 max, oxygen pulse, percent predicted peak heart rate for preoperative subjects compared with age- and gender-matched controls. Roest et al. also found

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Pediatr Cardiol Table 4 Paired t test results comparing exercise stress testing and MRI before and after surgery separated by age cohorts

n

Pre-surgery

Post-surgery

Change from pre-surgery

p value

Exercise stress testing in patients with age at surgery \25 years (n = 20) Exercise time (min)

20

11.1 ± 2.7

11.1 ± 2.0

0.03 ± 1.4

0.93

VO2 max (ml/kg/min)

20

29.2 ± 8.4

30.2 ± 7.2

1.01 ± 7.25

0.54

% predicted VO2 max

20

67.7 ± 19.5

70.6 ± 16.3

2.85 ± 16.5

0.45

% Predicted Peak HR

20

90.3 ± 10.1

92.7 ± 8.4

2.48 ± 6.91

0.13

Oxygen Pulse (mL/beat)

20

9.6 ± 4.5

9.8 ± 3.7

0.21 ± 1.99

0.68

VE/VCO2 slope

19

34.3 ± 5.7

33.1 ± 4.1

-1.16 ± 4.69

0.30

AT to VO2 max %

18

50.9 ± 13.1

50.4 ± 9.9

-0.44 ± 10.8

0.86

Exercise stress testing in patients with age at surgery C25 years (n = 6) Exercise time (min)

6

9.4 ± 2.6

9.4 ± 2.6

-0.01 ± 2.7

0.99

VO2 max (ml/kg/min)

6

23.1 ± 5.3

21.9 ± 6.9

-1.27 ± 2.62

0.29

% predicted VO2 max

6

57.8 ± 15.2

56.2 ± 19.5

-1.67 ± 6.65

0.57

% Predicted peak HR

6

84.6 ± 11.8

76.9 ± 14.8

-7.7 ± 20.1

0.39

Oxygen pulse (mL/beat)

4

9.3 ± 2.5

10.0 ± 3.5

0.73 ± 1.8

0.48

VE/VCO2 slope AT to VO2 max %

5 4

31.3 ± 2.6 45.0 ± 7.9

29.8 ± 1.0 46.0 ± 4.8

-1.50 ± 1.88 1.00 ± 8.41

0.15 0.83

Values expressed as mean ± standard deviation (range) VO2 max maximal oxygen consumption, HR heart rate, VE/VCO2 ventilatory equivalent ratio for carbon dioxide, AT anaerobic threshold

Table 5 Results from t tests comparing exercise stress testing before and after surgery between age cohorts Young cohort (surgical age \25 years) Pre-surgery exercise stress testing results Exercise time (min)

Old cohort (surgical age C25 years)

p value

11.1 ± 2.7

9.4 ± 2.6

0.20

VO2 max (ml/kg/min)

29.2 ± 8.4

23.1 ± 5.3

0.055

% Predicted peak HR

90.3 ± 10.1

84.6 ± 11.8

0.33

9.6 ± 4.5

9.3 ± 2.5

0.85

VE/VCO2 slope

34.3 ± 5.7

31.3 ± 2.6

0.12

% predicted VO2 max

67.7 ± 19.5

57.8 ± 15.2

0.22

AT to VO2 max %

50.9 ± 13.1

45.0 ± 7.9

0.24

Oxygen pulse (mL/beat)

Post-surgery exercise stress testing results Exercise time (min)

11.1 ± 2.0

9.4 ± 2.6

0.18

VO2 max (ml/kg/min)

30.2 ± 7.2

21.9 ± 6.9

0.030

% Predicted peak HR

92.7 ± 8.4

76.9 ± 14.8

0.047

9.8 ± 3.7

10.0 ± 3.5

0.92

VE/VCO2 slope

33.1 ± 4.1

29.8 ± 1.0

0.00

% predicted VO2 max

70.6 ± 16.3

56.2 ± 19.5

0.14

AT to VO2 max %

50.4 ± 9.9

46.0 ± 4.8

0.18

Oxygen pulse (mL/beat)

Values expressed as mean ± standard deviation VO2 max maximal oxygen consumption, HR heart rate, VE/VCO2 ventilatory equivalent ratio for carbon dioxide, AT anaerobic threshold

PVR. These include prolonged exposure of the ventricles to inappropriate loading conditions, persistent RV dysfunction after PVR, deconditioning of patients, altered pulmonary function, and chronotropic incompetence impairing effort tolerance [5, 7, 10, 32]. These proposals

suggest that PVR should be done sooner and that symptoms alone may not be a good indicator to determine PVR timing. In addition, our recent studies have demonstrated that evaluation of this patient population with pulmonary function testing and metabolic variables is helpful to

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Pediatr Cardiol Table 6 Results from t tests comparing exercise stress testing in the control sample between age cohorts

Controls \25 years old (n = 20)

Controls C25 years old (n = 6)

p value 0.23

Exercise time (min)

14.8 ± 3.0

13.4 ± 2.1

VO2 max (ml/kg/min)

41.6 ± 10.5

39.8 ± 6.2

0.61

% Predicted peak HR

93.3 ± 3.3

97.5 ± 5.8

0.14

Oxygen pulse (mL/beat)

13.3 ± 5.2

16.1 ± 3.3

0.16

Values expressed as mean ± standard deviation VO2 max maximal oxygen consumption, HR heart rate

determine the status of cardiopulmonary limitations. Abnormalities in pulmonary function were a major factor in limiting exercise capacity with severe PR before and after PVR. Conversely, those patients affected primarily from a cardiac standpoint stand to gain the most benefits from PVR [23]. Another reason to consider earlier PVR repair includes the finding that exercise capacity may be better preserved with earlier PVR. In our study, significant differences are seen when comparing the younger and older cohort after surgery. No significant differences in EST parameters are measured preoperatively; however, after surgery, the older cohort had a significant decrease in VO2 max and percent predicted peak heart rate compared with the younger cohort. This same age-related difference in EST parameters was not appreciated when comparing young and old controls, implying that this difference cannot be attributed strictly to the age difference between cohorts. Frigiola et al. [5] also found that younger subjects—using 17.5 years as the divider—were found to benefit more from PVR with improved LV filling and cardiac output, suggesting better preservation of exercise capacity with earlier timing of PVR. Evaluation for Pulmonary Valve Replacement Using Magnetic Resonance Imaging Our data support previous MRI findings of correction of RV dimensions without significant change in RVEF [7, 14, 20, 26–30]. Vliegen et al. suggest utilizing a separate measurement to evaluate net forward pulmonary flow instead of stroke volume to remove any confounding factors of regurgitant flow and shunting that may affect stroke volume. This is calculated by taking the difference from pulmonary forward flow and regurgitant flow (net pulmonary flow) and dividing by the RVEDV [14]. Performing those measurements for our patient population, there was a significant increase in net pulmonary flow post-PVR from 27.2 ± 4.9 to 48.8 ± 13.2 % (p = 0.0003). Frigiola et al. did find that RVEF significantly improved after PVR, along with RV dimensions. It was postulated that their patients’ RVEF improved due to relatively smaller RVEDV compared with other studies [5].

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The Dilemma of Optimal Timing of Pulmonary Valve Replacement The dilemma of PVR timing depends on multiple factors including clinical evaluation, test results, and on the center’s desire to preserve as much function as possible while not exposing individuals to a large surgical burden. Recommendations vary with respect to details, but the consensus is that PVR should be scheduled in early adulthood in those with severe PR and RV dysfunction [16, 31]. Predicting a favorable response after PVR correlates more with RV hemodynamics than chronological age, although these factors may be related. Patients undergoing PVR with an indexed RVEDV B 170 ml/m2 almost uniformly had normalization of RV volumes [26]. Of the patients in this study who underwent MRI, 10 out of 11 had an indexed RVEDV B 170 ml/m2, with all showing normalization of RV volumes. A recent article recommends consideration of PVR before the indexed RVEDV exceeds 163 ml/m2 [15]. Suggested guidelines for PVR timing in the face of significant PR include proceeding with an RVEDV:LVEDV ratio C1.5 in symptomatic patients or an RVEDV:LVEDV ratio C2 in asymptomatic patients [5]. Another guideline recommends those with moderate-tosevere PR undergo PVR with the presence of two or more of the following features: RVEDV index C160 ml/m2, RVESV index C70 ml/m2, LVEDV index C65 ml/m2, RVEF B 45 %, and presence of an RVOT aneurysm [9]. Besides preserving exercise capacity and increasing the chances for the improvement in RV dimensions, early PVR also allows for QRS stabilization and reduction in the risk of arrhythmias. The risk of sudden death is also decreased. Whether this is from a rhythm or altered hemodynamics standpoint is not clear [6, 7, 16, 25]. Study Limitations A limitation is the relatively small number of patients available for inclusion. Also, as stated above, the confounding factor of undergoing cardiothoracic surgery remains when comparing the patient group with healthy controls. The follow-up period of 1 year was evaluated in

Pediatr Cardiol

this study; however, longer follow-up periods are required to draw stronger conclusions from the study. Future Directions We hope to continue to perform EST and cardiac MRI on this population of post-PVR patients to determine whether their exercise capacities and ventricular hemodynamics will improve in the longer term. We would also like to evaluate the EST and MRI results for a cohort of patients who are status post-initial RVOT repair but without severe PR to use as a comparison for the study group. This would allow us to remove the confounding factor of the initial surgery when comparing the study group with healthy controls. In addition, we will begin routine serial EST of patients with a history of initial RVOT repair sooner and look for any signs of diminishing exercise capacity. This will better allow our group to determine the optimal timing for PVR to maximize the exercise capacity of these patients as shown in the age-related differences in this study.

Conclusion This study showed that patients who are status post-RVOT repair with severe PR do not have significantly improved exercise capacity and RV hemodynamics as we had hypothesized. While PVR can improve certain RV functional parameters, it does not improve ventricular function or exercise capacity, at least in the short term. However, while the RVEF measurement remained the same after PVR, this could be interpreted as improvement in hemodynamics in the face of markedly reduced RV end-diastolic volume and pulmonary artery RF, suggesting an increase in net forward pulmonary flow. The results of this study do suggest that serial EST in patients with severe PR following RVOT repair should be performed routinely to identify deteriorating exercise capacity in the face of RV dilation. Our age-specific data suggest that exercise capacity can be preserved at a higher level if PVR is performed before significant deterioration is allowed to develop. These data can then be used as an early indicator for the need for PVR and help clinicians decide the optimal surgical timing for their patients. It is also important to realize that the decisions to proceed with PVR are unique to each patient and situation and require gathering of data to assess quantitative measures such as ventricular function, valvar function, and chamber dimensions, along with clinical evaluations to assess qualitative measures including patient symptomatology, quality of life, and exercise capacity.

Conflict of interest of interest.

The authors declare that they have no conflict

Ethical standard All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study.

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The Effects of Pulmonary Valve Replacement for Severe Pulmonary Regurgitation on Exercise Capacity and Cardiac Function.

Patients may develop hemodynamic abnormalities after right ventricular outflow tract (RVOT) repair. Re-intervention timing remains a dilemma. This stu...
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