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Incremental Benefit of Cardiopulmonary Exercise Testing for the Prediction of Outcome in Stable Prevalent Pulmonary Arterial Hypertension Patients
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The Journal of Heart and Lung Transplantation, Vol 36, No 4S, April 2017
catheterization (RHC). Intraoperative values were measured with a Swan Ganz catheter. Differences in PAP (Δ mPAP, Δ PASP, and Δ PADP) at evaluation vs. at LTx were analyzed via independent t-tests. Primary graft dysfunction (PGD) was recorded at 48-72 hours post-LTx. Results: In total, 59 patients received bilateral LTx for obstructive or restrictive ESLD during this period. Of these, 23 (39%) were Group A and 36 (61%) were Group B. Median age was similar between groups (Group A: 63 years, Group B: 64 years, p= 0.83). Median lung allocation score was significantly higher in Group B. Group B had greater Δ mPAP and Δ PASP than Group A despite shorter waitlist time and time between RHC and LTx. Post-LTx length of stay (LOS) was higher in Group B, but intensive care unit LOS was comparable. 3 patients in Group B (8.3%) required cardiopulmonary bypass (CPB), but no patient in Group A required CPB. PGD Grade 3 affected a higher proportion of Group B (9/36, 25%) than Group A (3/23, 13%) (p= 0.33). 30-day mortality was 0% for both groups. Conclusion: Despite shorter waitlist time and time from RHC to LTx, patients with restrictive ESLD had much greater increase in mPAP and PASP while awaiting LTx, compared to obstructive ESLD. Those with restrictive ESLD will likely have significantly higher PAP at LTx than at RHC, which may translate to increased use of CPB at LTx and greater risk of PGD Grade 3.
LTx Patient Characteristics and Outcomes by Disease Group
Variable
Group A (Obstructive ESLD) (n= 23) Median (IQR)
Group B (Restrictive ESLD) (n= 36) Median (IQR)
P-value1
Male sex, n (%)
10 (43.5)
23 (63.9)
0.18
Lung allocation score
33.1 (32.7, 35.7)
42.5 (36.1, 49.2)
< 0.001
Time on waitlist, days
20 (10, 66)
11 (3, 20.5)
0.012
Duration between RHC and LTx
82 (42, 188)
50.5 (26.5, 87)
0.051
Mean pulmonary artery pressure at evaluation, mmHg
21 (17, 24)
16 (10.5, 23)
0.081
Pulmonary artery systolic pressure at evaluation, mmHg
34 (26 ,44)
41 (36, 50)
0.004
Pulmonary artery diastolic pressure at evaluation, mmHg
21 (17, 26)
24 (21, 27)
0.18
Mean pulmonary artery pressure at LTx, mmHg
26 (22, 32)
30.5 (26, 34)
0.030
Pulmonary artery 34 (26 ,44) systolic pressure at LTx, mmHg
41 (36, 50)
0.004
Pulmonary artery 21 (17, 26) diastolic pressure at LTx, mmHg
24 (21, 27)
0.18
Δ mean pulmonary artery pressure, mmHg
6 (2, 13)
13 (6.5, 20.5)
0.007
Δ pulmonary artery systolic pressure, mmHg
5 (-4, 19)
14 (2.5, 26)
0.025
Δ pulmonary artery diastolic pressure, mmHg
4 (-3, 12)
8 (3, 12)
0.21
Primary graft dysfunction Grade 3 at 48-72 hours post-LTx, n (%)
3 (13)
9 (25)
0.33
Cardiopulmonary bypass use, n (%)
0 (0.0)
3 (8.3)
0.27
ECMO for PGD, n (%)
1 (4.4)
1( 78) Incremental Benefit of Cardiopulmonary Exercise Testing for the Prediction of Outcome in Stable Prevalent Pulmonary Arterial Hypertension Patients R. Badagliacca ,1 S. Papa,1 R. Poscia,1 G. Valli,1 B. Pezzuto,1 G. Manzi,1 P. Palange,2 F. Fedele,1 C.D. Vizza.1 1Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy; 2Clinical Medicine, Sapienza University of Rome, Rome, Italy. Purpose: In pulmonary arterial hypertension (PAH) escalation of therapy is mainly based on clinical and hemodynamic evaluation. We aimed to evaluate the incremental prognostic value of cardiopulmonary exercise test (CPET) on long-term prognosis in stable prevalent patients. Methods: Sixty-three prevalent PAH patients were enrolled as a derivation cohort if free from clinical worsening (CW) after 1-year treatment from diagnosis. A prognostic model was constructed and validated in a different time-set cohort of prevalent PAH patients, in WHO class I-II, cardiac index (CI) ≥ 2.5 and right atrial pressure (RAP) < 8mmHg after 1-year treatment. Discrimination and calibration were assessed. Results: During a mean period of 490±237 days, 25 patients of the derivation cohort experienced CW (39.7%). ∆WHO class, ∆CI and RAP were independent predictors of CW (Model-1). With addition of CPET variables (Model2), VO2peak and ∆CI independently improved the power of the prognostic model (AUC: 0.67 vs 0.80, respectively; p< 0.001). ROC-derived cut-points, ∆CI< 0.45 l/min/m2 and VO2peak ≤ 15 ml/kg/min, were used for CW detection. In the validation cohort 20/80 patients experienced CW (25%) during 428±210 days. Group 1 (> 15 VO2peak + ≥ 0.45 ∆CI), Group 2 (> 15 VO2peak + < 0.45 ∆CI), Group 3 (≤ 15 VO2peak + ≥ 0.45 ∆CI) and Group 4 (≤ 15 VO2peak + < 0.45 ∆CI) showed 100%-100%, 100%-83%, 75%-56%, 70%46%, event-free survival at 1-2 years, respectively. Group 3-4 showed 5.6 and 7.8 increase in the hazard ratio, respectively, compared with the pooled Group 1-2 (p= 0.003). The combination of VO2peak > 15mmHg/kg/min and ∆CI ≥ 0.45 l/min/m2 had high sensitivity (100%) and negative predictive value (100%). Discrimination (c-statistic 0.79, derivation cohort; 0.77, validation cohort) and calibration (intercept 0.01; slope 0.94) were highly acceptable. Conclusion: Low ∆CI+low VO2peak and high ∆CI+low VO2peak identify patients at high risk of CW, suggesting a more aggressive therapeutic approach. 1( 79)
2 (5.6)
0.83
Post-LTx length of stay, 12 (10, 14) days
14 (12, 19.5)
0.039
Intensive care unit length of stay, days
9 (4.5, 19.5)
0.12
7 (4, 12)
Abbreviations: ESLD: End-stage lung disease, IQR: Interquartile range, LTx: lung transplantation, PGD: primary graft dysfunction, RHC: right heart catheterization 1 Wilcoxon Rank Sum used for continuous variables, and Fisher’s exact used for categorical variables.
Pediatric Marginal Donor Hearts: National Use and Center-Specific Variability A.K. Morrison ,1 D. Tumin,2 D. Hayes Jr.,3 C. Phelps,1 J. Tobias,2 R.J. Gajarski,1 D. Nandi.1 1The Heart Center, Nationwide Children's Hospital, Columbus, OH; 2Department of Anesthesiology & Pain Medicine, Nationwide Children's Hospital, Columbus, OH; 3Section of Pulmonary Medicine, Nationwide Children's Hospital, Columbus, OH. Purpose: Donor organ shortages contribute to high mortality in pediatric patients awaiting heart transplant. We examined national trends in pediatric donor use, the prevalence of potentially marginal characteristics among donor organs, and center-level variation in marginal donor use. Methods: UNOS data were queried for all heart donors < 18 years old from 2006 to 2015. A logistic regression model of donor heart recovery for transplant was created using previously cited marginal characteristics: LV dysfunction (EF < 50%), inotrope use, cerebrovascular death, CDC high risk status, female gender, hypertension, and diabetes, and adjusted for donor age. Center-level variation in and possible factors associated with marginal donor use for recipients aged < 18 years were assessed among 47 centers performing ≥ 10 pediatric transplants over the study period. Results: Of 8,910 pediatric hearts offered for donation from 2006 to 2015, 3,942 (44%) were recovered for transplant. The proportion of pediatric donor hearts used in pediatric recipients has increased over time, from 24% in 2006 to 39% in 2015 (p< 0.001). LV dysfunction, inotrope use (≥ 3), hypertension, and diabetes were the only marginal characteristics associated with donor organ non-use. Across centers, the median proportion of donor hearts used with one of these characteristics was 5% (range 0-12%). Neither a center’s 1-year mortality, nor their transplant volume, was associated with center proportion of marginal donor use.
The Journal of Heart and Lung Transplantation, Vol 36, No 4S, April 2017
catheterization (RHC). Intraoperative values were measured with a Swan Ganz catheter. Differences in PAP (Δ mPAP, Δ PASP, and Δ PADP) at evaluation vs. at LTx were analyzed via independent t-tests. Primary graft dysfunction (PGD) was recorded at 48-72 hours post-LTx. Results: In total, 59 patients received bilateral LTx for obstructive or restrictive ESLD during this period. Of these, 23 (39%) were Group A and 36 (61%) were Group B. Median age was similar between groups (Group A: 63 years, Group B: 64 years, p= 0.83). Median lung allocation score was significantly higher in Group B. Group B had greater Δ mPAP and Δ PASP than Group A despite shorter waitlist time and time between RHC and LTx. Post-LTx length of stay (LOS) was higher in Group B, but intensive care unit LOS was comparable. 3 patients in Group B (8.3%) required cardiopulmonary bypass (CPB), but no patient in Group A required CPB. PGD Grade 3 affected a higher proportion of Group B (9/36, 25%) than Group A (3/23, 13%) (p= 0.33). 30-day mortality was 0% for both groups. Conclusion: Despite shorter waitlist time and time from RHC to LTx, patients with restrictive ESLD had much greater increase in mPAP and PASP while awaiting LTx, compared to obstructive ESLD. Those with restrictive ESLD will likely have significantly higher PAP at LTx than at RHC, which may translate to increased use of CPB at LTx and greater risk of PGD Grade 3.
LTx Patient Characteristics and Outcomes by Disease Group
Variable
Group A (Obstructive ESLD) (n= 23) Median (IQR)
Group B (Restrictive ESLD) (n= 36) Median (IQR)
P-value1
Male sex, n (%)
10 (43.5)
23 (63.9)
0.18
Lung allocation score
33.1 (32.7, 35.7)
42.5 (36.1, 49.2)
< 0.001
Time on waitlist, days
20 (10, 66)
11 (3, 20.5)
0.012
Duration between RHC and LTx
82 (42, 188)
50.5 (26.5, 87)
0.051
Mean pulmonary artery pressure at evaluation, mmHg
21 (17, 24)
16 (10.5, 23)
0.081
Pulmonary artery systolic pressure at evaluation, mmHg
34 (26 ,44)
41 (36, 50)
0.004
Pulmonary artery diastolic pressure at evaluation, mmHg
21 (17, 26)
24 (21, 27)
0.18
Mean pulmonary artery pressure at LTx, mmHg
26 (22, 32)
30.5 (26, 34)
0.030
Pulmonary artery 34 (26 ,44) systolic pressure at LTx, mmHg
41 (36, 50)
0.004
Pulmonary artery 21 (17, 26) diastolic pressure at LTx, mmHg
24 (21, 27)
0.18
Δ mean pulmonary artery pressure, mmHg
6 (2, 13)
13 (6.5, 20.5)
0.007
Δ pulmonary artery systolic pressure, mmHg
5 (-4, 19)
14 (2.5, 26)
0.025
Δ pulmonary artery diastolic pressure, mmHg
4 (-3, 12)
8 (3, 12)
0.21
Primary graft dysfunction Grade 3 at 48-72 hours post-LTx, n (%)
3 (13)
9 (25)
0.33
Cardiopulmonary bypass use, n (%)
0 (0.0)
3 (8.3)
0.27
ECMO for PGD, n (%)
1 (4.4)
1( 78) Incremental Benefit of Cardiopulmonary Exercise Testing for the Prediction of Outcome in Stable Prevalent Pulmonary Arterial Hypertension Patients R. Badagliacca ,1 S. Papa,1 R. Poscia,1 G. Valli,1 B. Pezzuto,1 G. Manzi,1 P. Palange,2 F. Fedele,1 C.D. Vizza.1 1Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy; 2Clinical Medicine, Sapienza University of Rome, Rome, Italy. Purpose: In pulmonary arterial hypertension (PAH) escalation of therapy is mainly based on clinical and hemodynamic evaluation. We aimed to evaluate the incremental prognostic value of cardiopulmonary exercise test (CPET) on long-term prognosis in stable prevalent patients. Methods: Sixty-three prevalent PAH patients were enrolled as a derivation cohort if free from clinical worsening (CW) after 1-year treatment from diagnosis. A prognostic model was constructed and validated in a different time-set cohort of prevalent PAH patients, in WHO class I-II, cardiac index (CI) ≥ 2.5 and right atrial pressure (RAP) < 8mmHg after 1-year treatment. Discrimination and calibration were assessed. Results: During a mean period of 490±237 days, 25 patients of the derivation cohort experienced CW (39.7%). ∆WHO class, ∆CI and RAP were independent predictors of CW (Model-1). With addition of CPET variables (Model2), VO2peak and ∆CI independently improved the power of the prognostic model (AUC: 0.67 vs 0.80, respectively; p< 0.001). ROC-derived cut-points, ∆CI< 0.45 l/min/m2 and VO2peak ≤ 15 ml/kg/min, were used for CW detection. In the validation cohort 20/80 patients experienced CW (25%) during 428±210 days. Group 1 (> 15 VO2peak + ≥ 0.45 ∆CI), Group 2 (> 15 VO2peak + < 0.45 ∆CI), Group 3 (≤ 15 VO2peak + ≥ 0.45 ∆CI) and Group 4 (≤ 15 VO2peak + < 0.45 ∆CI) showed 100%-100%, 100%-83%, 75%-56%, 70%46%, event-free survival at 1-2 years, respectively. Group 3-4 showed 5.6 and 7.8 increase in the hazard ratio, respectively, compared with the pooled Group 1-2 (p= 0.003). The combination of VO2peak > 15mmHg/kg/min and ∆CI ≥ 0.45 l/min/m2 had high sensitivity (100%) and negative predictive value (100%). Discrimination (c-statistic 0.79, derivation cohort; 0.77, validation cohort) and calibration (intercept 0.01; slope 0.94) were highly acceptable. Conclusion: Low ∆CI+low VO2peak and high ∆CI+low VO2peak identify patients at high risk of CW, suggesting a more aggressive therapeutic approach. 1( 79)
2 (5.6)
0.83
Post-LTx length of stay, 12 (10, 14) days
14 (12, 19.5)
0.039
Intensive care unit length of stay, days
9 (4.5, 19.5)
0.12
7 (4, 12)
Abbreviations: ESLD: End-stage lung disease, IQR: Interquartile range, LTx: lung transplantation, PGD: primary graft dysfunction, RHC: right heart catheterization 1 Wilcoxon Rank Sum used for continuous variables, and Fisher’s exact used for categorical variables.
Pediatric Marginal Donor Hearts: National Use and Center-Specific Variability A.K. Morrison ,1 D. Tumin,2 D. Hayes Jr.,3 C. Phelps,1 J. Tobias,2 R.J. Gajarski,1 D. Nandi.1 1The Heart Center, Nationwide Children's Hospital, Columbus, OH; 2Department of Anesthesiology & Pain Medicine, Nationwide Children's Hospital, Columbus, OH; 3Section of Pulmonary Medicine, Nationwide Children's Hospital, Columbus, OH. Purpose: Donor organ shortages contribute to high mortality in pediatric patients awaiting heart transplant. We examined national trends in pediatric donor use, the prevalence of potentially marginal characteristics among donor organs, and center-level variation in marginal donor use. Methods: UNOS data were queried for all heart donors < 18 years old from 2006 to 2015. A logistic regression model of donor heart recovery for transplant was created using previously cited marginal characteristics: LV dysfunction (EF < 50%), inotrope use, cerebrovascular death, CDC high risk status, female gender, hypertension, and diabetes, and adjusted for donor age. Center-level variation in and possible factors associated with marginal donor use for recipients aged < 18 years were assessed among 47 centers performing ≥ 10 pediatric transplants over the study period. Results: Of 8,910 pediatric hearts offered for donation from 2006 to 2015, 3,942 (44%) were recovered for transplant. The proportion of pediatric donor hearts used in pediatric recipients has increased over time, from 24% in 2006 to 39% in 2015 (p< 0.001). LV dysfunction, inotrope use (≥ 3), hypertension, and diabetes were the only marginal characteristics associated with donor organ non-use. Across centers, the median proportion of donor hearts used with one of these characteristics was 5% (range 0-12%). Neither a center’s 1-year mortality, nor their transplant volume, was associated with center proportion of marginal donor use.