Background
Methods
Patient selection
Right heart catheterization
Echocardiography
Cardiopulmonary exercise testing
Ethics statement
Statistical methods
Results
Study population (Table 1)
mean ± SD or n (%) | ||||||
---|---|---|---|---|---|---|
Demographics | Age |
(years)
| 53 | ± | 14.65 | |
BMI |
(kg/m
2
)
| 27.9 | ± | 5.69 | ||
Gender | male |
n (%)
| 21 | (38.9) | ||
female |
n (%)
| 33 | (61.1) | |||
Diagnosis | IPAH |
n (%)
| 31 | (57.4) | ||
HPAH |
n (%)
| 8 | (14.8) | |||
APAH |
n (%)
| 12 | (22.2) | |||
CTEPH |
n (%)
| 3 | (5.6) | |||
WHO functional class | I |
n (%)
| 1 | (1.9) | ||
II |
n (%)
| 36 | (66.7) | |||
III |
n (%)
| 17 | (31.5) | |||
PAH-targeted medication | Endothelin receptor antagonist | 40 | (74.1) | |||
Phosphodiesterase-5-inhibitors | 38 | (70.4) | ||||
Soluble guanylate cyclase-stimulator | 8 | (13.0) | ||||
Prostanoids | 6 | (14.8) | ||||
Calcium channel blockers | 2 | (03.7) | ||||
Combination therapy | ||||||
Mono |
n (%)
| 18 | (33.3) | |||
Double |
n (%)
| 31 | (57.4) | |||
Triple |
n (%)
| 5 | (9.3) | |||
RHC | Rest | mPAP |
(mmHg)
| 35.5 | ± | 11.69 |
sPAP |
(mmHg)
| 57.6 | ± | 20.87 | ||
dPAP |
(mmHg)
| 23 | ± | 7.87 | ||
PCWP |
(mmHg)
| 10 | ± | 3.54 | ||
PVR |
(dyn*sec*cm
−5
)
| 393.4 | ± | 235.03 | ||
CO |
(l/min)
| 5.8 | ± | 1.61 | ||
CI |
(l/min/m
2
)
| 3 | ± | 0.73 | ||
SVI |
(ml/m
2
)
| 41.1 | ± | 10.2 | ||
25 W | ∆ CI |
(l/min/m
2
)
| 1.2 | ± | 0.67 | |
50 W | ∆ CI |
(l/min/m
2
)
| 2 | ± | 0.93 | |
75 W | ∆ CI |
(l/min/m
2
)
| 2.6 | ± | 1.15 | |
Peak | mPAP |
(mmHg)
| 56.5 | ± | 15.91 | |
sPAP |
(mmHg)
| 90.2 | ± | 28.36 | ||
dPAP |
(mmHg)
| 36.1 | ± | 11.56 | ||
CO |
(l/min)
| 10.2 | ± | 3.49 | ||
CI |
(l/min/m
2
)
| 5.3 | ± | 1.59 | ||
SVI |
(ml/m
2
)
| 47.2 | ± | 13.9 | ||
Echocardiography | RV area |
(cm
2
)
| 20.1 | ± | 5.59 | |
RA area |
(cm
2
)
| 16.8 | ± | 6.62 | ||
TAPSE |
(cm)
| 2.3 | ± | 0.38 | ||
Cardiopulmonary exercise testing (CPET) | peak V’O2 |
(ml/min)
| 1126 | ± | 428.88 | |
peak V’O2/kg |
(ml/min/kg)
| 14.1 | ± | 3.92 | ||
sPAP Max |
(mmHg)
| 81.8 | ± | 27.87 | ||
6-MWD |
(m)
| 423 | ± | 113.09 | ||
Laboratory analysis | NT-proBNP |
(pg/ml)
| 470.3 | ± | 856.74 | |
Pulmonary function test (PFT) | DLCOc SB |
(% Soll)
| 58.6 | ± | 17.25 | |
DLCOc VA |
(% Soll)
| 70.42 | ± | 20.00 |
n | RA area ≤ 16 cm2 | n | RA area > 16 cm2 | p-value | n | RV area ≤ 20 cm2 | n | RV area > 20 cm2 | p-value | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Demographics | Age |
(years)
| 33 | 53.6 | ± | 14.4 | 21 | 52.1 | ± | 15.3 | 0.71 | 30 | 51.4 | ± | 13.7 | 24 | 55.1 | ± | 15.8 | 0.354 | |||
BMI |
(kg/m
2
)
| 33 | 28.3 | ± | 6.5 | 21 | 27.3 | ± | 4.3 | 0.537 | 30 | 27.5 | ± | 5.5 | 24 | 28.4 | ± | 6.1 | 0.591 | ||||
6-MWD |
(m)
| 32 | 429 | ± | 124 | 21 | 414 | ± | 97 | 0.655 | 30 | 436 | ± | 127 | 23 | 406 | ± | 92 | 0.350 | ||||
PAH-targeted medication | ERA | 24 | (72.7%) | 16 | (76.2%) | 1.0 | 22 | (73.3%) | 18 | (75%) | 1.0 | ||||||||||||
PDE5-I | 22 | (66.7%) | 16 | (76.2%) | 0.549 | 21 | (70%) | 17 | (70.8%) | 1.0 | |||||||||||||
sGC stimulator | 3 | (9.1%) | 5 | (23.8%) | 0.238 | 3 | (10%) | 5 | (20.8%) | 0.443 | |||||||||||||
Prostanoids | 3 | (9.1%) | 3 | (14.3%) | 0.667 | 2 | (6.7%) | 4 | (16.7%) | 0.389 | |||||||||||||
Calcium channel blockers | 2 | (6.1%) | 0 | 0.516 | 2 | (6.7%) | 0 | 0.497 | |||||||||||||||
Combination therapy | Mono |
n (%)
| 13 | (39.4%) | 5 | (23.8%) | 0.102 | 11 | (36.7%) | 7 | (29.2%) | 0.414 | |||||||||||
Double |
n (%)
| 17 | (51.5%) | 14 | (66.7%) | 17 | (56.7%) | 14 | (58.3%) | ||||||||||||||
Triple |
n (%)
| 3 | (9.1%) | 2 | (9.5%) | 2 | (6.6%) | 3 | (12.5%) | ||||||||||||||
Echocardiography | RV area |
(cm
2
)
| 33 | 17.3 | ± | 3.9 | 21 | 24.6 | ± | 4.9 | < 0.0001 | * | 30 | 16.3 | ± | 3.1 | 24 | 25.0 | ± | 4.0 | < 0.0001 | * | |
RA area |
(cm
2
)
| 33 | 13.2 | ± | 2.7 | 21 | 22.4 | ± | 7.1 | < 0.0001 | * | 30 | 13.3 | ± | 3.2 | 24 | 21.1 | ± | 7.2 | < 0.0001 | * | ||
sPAP |
(mmHg)
| 33 | 42 | ± | 16 | 21 | 57 | ± | 17 | 0.003 | * | 30 | 42 | ± | 12 | 24 | 56 | 20 | 0.006 | * | |||
TAPSE |
(cm)
| 33 | 2.4 | ± | 0.4 | 21 | 2.3 | ± | 0.4 | 0.362 | 30 | 2.4 | ± | 0.4 | 24 | 2.3 | ± | 0.4 | 0.204 | ||||
Cardiopulmonary Exercise Testing | peak V’O2 |
(ml/min)
| 33 | 1155 | ± | 495 | 21 | 1080 | ± | 302 | 0.536 | 30 | 1144 | ± | 435 | 24 | 1103 | ± | 429 | 0.730 | |||
peak V’O2/kg |
(ml/min/kg)
| 33 | 14.5 | ± | 4.1 | 21 | 13.4 | ± | 3.7 | 0.321 | 30 | 14.7 | ± | 3.6 | 24 | 13.2 | ± | 4.2 | 0.166 | ||||
Laboratory analysis | NT-proBNP |
(pg/ml)
| 33 | 191 | ± | 231 | 20 | 931 | ± | 1266 | 0.018 | * | 30 | 145 | ± | 125 | 23 | 895 | ± | 1191 | 0.006 | * | |
Pulmonary function test | DLCOc SB |
(% Soll)
| 30 | 58.6 | ± | 18.6 | 18 | 58.6 | ± | 15.2 | 0.988 | 27 | 60.5 | ± | 15.3 | 21 | 56.2 | ± | 19.6 | 0.398 | |||
DLCOc VA |
(% Soll)
| 30 | 69.0 | ± | 21.2 | 18 | 72.8 | ± | 18.1 | 0.522 | 27 | 70.1 | ± | 19.3 | 21 | 70.8 | ± | 21.3 | 0.906 | ||||
RHC | Rest | mPAP |
(mmHg)
| 33 | 32 | ± | 10 | 21 | 41 | ± | 13 | 0.012 | * | 30 | 32 | ± | 9 | 24 | 40 | ± | 13 | 0.014 | * |
sPAP |
(mmHg)
| 33 | 51 | ± | 17 | 21 | 68 | ± | 22 | 0.002 | * | 30 | 51 | ± | 16 | 24 | 66 | ± | 24 | 0.013 | * | ||
dPAP |
(mmHg)
| 33 | 21 | ± | 6 | 21 | 26 | ± | 9 | 0.032 | * | 30 | 21 | ± | 6 | 24 | 26 | ± | 9 | 0.018 | * | ||
PAWP |
(mmHg)
| 33 | 10 | ± | 3 | 21 | 10 | ± | 4 | 0.514 | 30 | 10 | ± | 3 | 24 | 10 | ± | 4 | 0.852 | ||||
PVR |
(dyn*sec*cm
− 5
)
| 33 | 335 | ± | 201 | 21 | 486 | ± | 259 | 0.03 | * | 30 | 311 | ± | 149 | 24 | 496 | ± | 282 | 0.006 | * | ||
CI |
(l/min/m
2
)
| 33 | 3.08 | ± | 0.63 | 21 | 2.93 | ± | 0.88 | 0.470 | 30 | 3.19 | ± | 0.67 | 24 | 2.82 | ± | 0.77 | 0.062 | ||||
HR |
(1/min)
| 33 | 74 | ± | 12 | 21 | 76 | ± | 12 | 0.480 | 30 | 75 | ± | 10 | 24 | 75 | ± | 13 | 0.927 | ||||
SV |
(ml)
| 33 | 79.4 | ± | 21.2 | 21 | 77.1 | ± | 25.4 | 0.716 | 30 | 80.1 | ± | 19.0 | 24 | 76.4 | ± | 27.0 | 0.556 | ||||
SVI |
(ml/m
2
)
| 33 | 42.2 | ± | 8.4 | 21 | 39.3 | ± | 12.6 | 0.317 | 30 | 42.9 | ± | 8.4 | 24 | 38.8 | ± | 11.9 | 0.142 | ||||
25 W | ∆ CI |
(l/min/m
2
)
| 31 | 1.4 | ± | 0.7 | 20 | 0.9 | ± | 0.5 | 0.008 | * | 28 | 1.3 | ± | 0.7 | 23 | 1.0 | ± | 0.6 | 0.114 | ||
HR |
(1/min)
| 31 | 91 | ± | 18 | 20 | 93 | ± | 12 | 0.572 | 28 | 91 | ± | 18 | 23 | 93 | ± | 13 | 0.623 | ||||
∆ SV |
(ml)
| 31 | 14.6 | ± | 20.4 | 20 | 6.2 | ± | 12.3 | 0.105 | 28 | 15.0 | ± | 21.5 | 23 | 6.9 | ± | 11.5 | 0.112 | ||||
50 W | ∆ CI |
(l/min/m
2
)
| 31 | 2.2 | ± | 1.0 | 18 | 1.6 | ± | 0.7 | 0.027 | * | 28 | 2.28 | ± | 0.91 | 21 | 1.51 | ± | 0.76 | 0.003 | * | |
HR |
(1/min)
| 31 | 103 | ± | 17 | 18 | 105 | ± | 17 | 0.639 | 28 | 102 | ± | 18 | 21 | 106 | ± | 15 | 0.345 | ||||
∆ SV |
(ml)
| 31 | 18.0 | ± | 22.7 | 18 | 7.2 | ± | 13.1 | 0.041 | * | 28 | 21.0 | ± | 22.5 | 21 | 4.7 | ± | 12.0 | 0.002 | * | ||
75 W | ∆ CI |
(l/min/m
2
)
| 18 | 2.9 | ± | 1.2 | 9 | 2.0 | ± | 0.6 | 0.043 | * | 16 | 2.93 | ± | 1.17 | 11 | 2.09 | ± | 0.96 | 0.060 | ||
HR |
(1/min)
| 18 | 113 | ± | 16 | 9 | 112 | ± | 12 | 0.813 | 16 | 111 | ± | 17 | 11 | 115 | ± | 10 | 0.541 | ||||
∆ SV |
(ml)
| 18 | 22.2 | ± | 18.1 | 9 | 7.4 | ± | 18.1 | 0.045 | * | 16 | 25.0 | ± | 14.2 | 11 | 6.0 | ± | 18.2 | 0.005 | * | ||
Peak | mPAP |
(mmHg)
| 33 | 54 | ± | 15 | 21 | 61 | ± | 17 | 0.115 | 30 | 54 | ± | 15 | 24 | 60 | ± | 17 | 0.124 | |||
sPAP |
(mmHg)
| 33 | 84 | ± | 26 | 21 | 100 | ± | 30 | 0.049 | * | 30 | 85 | ± | 25 | 24 | 97 | ± | 31 | 0.144 | |||
dPAP |
(mmHg)
| 33 | 35 | ± | 12 | 21 | 38 | ± | 11 | 0.254 | 30 | 34 | ± | 12 | 24 | 39 | ± | 10 | 0.111 | ||||
CI |
(l/min/m
2
)
| 33 | 5.62 | ± | 1.57 | 21 | 4.80 | ± | 1.52 | 0.049 | * | 30 | 5.92 | ± | 1.43 | 24 | 4.52 | ± | 1.45 | 0.001 | * | ||
∆ CI |
(l/min/m
2
)
| 33 | 2.54 | ± | 1.42 | 21 | 1.86 | ± | 0.83 | 0.033 | * | 30 | 2.73 | ± | 1.34 | 24 | 1.7 | ± | 0.88 | 0.002 | * | ||
SV |
(ml)
| 33 | 93.3 | ± | 26.7 | 21 | 86.0 | ± | 33.8 | 0.383 | 30 | 0.1 | ± | 0.027 | 24 | 0.08 | ± | 0.029 | 0.007 | * | |||
PAC |
(ml/mmHg)
| 33 | 39.0 | ± | 13.7 | 21 | 33.1 | ± | 12.4 | 0.108 | 30 | 39.5 | ± | 11.2 | 24 | 33.2 | ± | 15.3 | 0.027 | * | |||
SVI | (l/m2) | 33 | 49.4 | ± | 11.5 | 21 | 43.7 | ± | 16.6 | 0.141 | 30 | 53.1 | ± | 11.1 | 24 | 39.8 | ± | 13.7 | < 0.001 | * |
Factors associated with right heart size and RV output reserve (Tables 3 and 4)
Right atrial area | Right ventricular area | |||||||
---|---|---|---|---|---|---|---|---|
n | pearson’s R | p-value | n | pearson’s R | p-value | |||
Univariate analysis | ||||||||
Age | 54 | 0.193 | 0.162 | 54 | - 0.048 | 0.209 | ||
Body mass index | 54 | 0.181 | 0.190 | 54 | 0.733 | 0.129 | ||
6-min walking distance | 53 | - 0.108 | 0.441 | 53 | - 0.121 | 0.387 | ||
NT-proBNP | 53 | 0.539 | < 0.001 | * | 53 | 0.538 | < 0.001 | * |
Echocardiography | ||||||||
Systolic pulmonary arterial pressure | 54 | 0.307 | 0.024 | * | 54 | 0.567 | < 0.001 | * |
Right atrial area | – | 54 | 0.703 | < 0.001 | * | |||
Right ventricular area | 54 | 0.703 | < 0.001 | * | – | |||
Tricuspid annular plane systolic excursion | 54 | - 0.128 | 0.356 | 54 | - 0.082 | 0.554 | ||
Cardiopulmonary exercise testing | ||||||||
Peak oxygen consumption (V’O2) | 54 | 0.042 | 0.736 | 54 | 0.051 | 0.713 | ||
Peak oxygen consumption/kg (V’O2/kg) | 54 | - 0.199 | 0.149 | 54 | - 0.227 | 0.099 | ||
Right heart catheter | ||||||||
rest | ||||||||
Mean pulmonary arterial pressure | 54 | 0.176 | 0.202 | 54 | 0.544 | < 0.001 | * | |
Cardiac Output | 54 | - 0.028 | 0.839 | 54 | - 0.052 | 0.709 | ||
Cardiac Index | 54 | - 0.209 | 0.129 | 54 | - 0.281 | 0.040 | * | |
Pulmonary arterial wedge pressure | 54 | 0.025 | 0.857 | 54 | - 0.101 | 0.467 | ||
Pulmonary vascular resistance | 54 | 0.175 | 0.206 | 54 | 0.508 | < 0.001 | * | |
Stroke volume index | 54 | −0.244 | 0.076 | 54 | −0.301 | 0.027 | * | |
exercise | ||||||||
Mean pulmonary arterial pressure | 54 | 0.097 | 0.486 | 54 | 0.419 | 0.002 | * | |
Cardiac Output | 54 | - 0.177 | 0.200 | 54 | - 0.223 | 0.104 | ||
Cardiac Index | 54 | - 0.344 | 0.011 | * | 54 | - 0.427 | 0.001 | * |
∆ CI peak | 54 | - 0.313 | 0.021 | * | 54 | - 0.376 | 0.005 | * |
Stroke volume index | 54 | −0.264 | 0.054 | 54 | −0.407 | 0.002 | * | |
Lung function / Diffusing capacity | ||||||||
DLCOc SB | 48 | - 0.052 | 0.723 | 48 | - 0.003 | 0.982 | ||
DLCOc /VA | 48 | 0.176 | 0.231 | 48 | 0.137 | 0.352 |
Univariate analysis (∆ CI Peak) | n | pearson’s R | p-value | |
---|---|---|---|---|
Age | 54 | 0.424 | 0.001 | * |
Body mass index | 54 | 0.092 | 0.506 | |
6 min walking distance | 54 | 0.278 | 0.044 | * |
NT-proBNP | 54 | - 0.360 | 0.008 | * |
Echocardiography | ||||
Systolic pulmonary arterial pressure | 54 | - 0.462 | < 0.001 | * |
Right atrial area | 54 | - 0.313 | 0.021 | * |
Right ventricular area | 54 | - 0.376 | 0.005 | * |
Tricuspid annular plane systolic excursion | 54 | 0.065 | 0.64 | |
Cardiopulmonary exercise testing | ||||
peak oxygen consumption (V’O2) | 54 | 0.466 | < 0.001 | * |
peak oxygen consumption/kg (V’O2/kg) | 54 | 0.380 | 0.005 | * |
Right heart catheter | ||||
rest | ||||
mean pulmonary arterial pressure | 54 | - 0.288 | 0.035 | * |
Cardiac Output | 54 | 0.282 | 0.039 | * |
Cardiac Index | 54 | 0.223 | 0.106 | |
Pulmonary arterial wedge pressure | 54 | - 0.016 | 0.906 | |
pulmonary vascular resistance | 54 | - 0.366 | 0.006 | * |
exercise | ||||
mean pulmonary arterial pressure | 54 | - 0.073 | 0.598 | |
Cardiac Output | 54 | 0.839 | < 0.001 | * |
Cardiac Index | 54 | 0.894 | < 0.001 | * |
Lung function / Diffusing capacity | ||||
DLCOc SB | 48 | 0.361 | 0.012 | * |
DLCOc / VA | 48 | 0.342 | 0.017 | * |
Multivariate analysis | ||||
Logistic Regression (stepwise forward selection) | ||||
∆ CI exrcise (dichotomous) | Exp (B) | |||
Right ventricular area | 47 | 0.863 | 0.027 | * |
Linear Regression (stepwise forward selection) | ||||
∆ CI Peak (continuous) | pearson’s R | |||
Right ventricular area | 47 | - 0.360 | 0.003 | * |
Age | 47 | - 0.412 | 0.001 | * |