Background
Methods
Study design
Study population
Analysis of echocardiography
Data collection
Statistics
Results
Mean ± standard deviation or n and (%) | 95% CI (mean) | median and interquartile ranges | |||
---|---|---|---|---|---|
Variable | N | lower limit | upper limit | ||
Demographics | |||||
Age [years] | 71 | 59.1 ± 13.42 | 56.0 | 62.3 | 60 [50; 71] |
Height [cm] | 71 | 167.6 ± 9.89 | 165.2 | 169.9 | 168 [160; 174] |
Weight [kg] | 71 | 76.91 ± 17.53 | 72.77 | 81.06 | 73.0 [65; 87] |
BMI [kg/m2] | 71 | 27.26 ± 5.04 | 26.06 | 28.45 | 26.42 [24; 29.05] |
gender [female n (%)] | 38 (53.5%) | ||||
Pulmonary hypertension etiology | |||||
Idiopathic PAH | 14 (19.7%) | ||||
CTD-APAH | 10 (14.1%) | ||||
Other PAH | 8 (11.3%) | ||||
Chronic thromboembolic pulmonary hypertension | 39 (54.9%) | ||||
WHO functional class | |||||
II | 17 (23.9%) | ||||
III | 54 (76.1%) | ||||
Pulmonary hypertension targeted treatment | |||||
treatment naÏve | 52 (73%) | ||||
Endothelin-Receptor-Antagonist | 14 (20%) | ||||
Phosphodiesterase-5-inhibitor | 5 (7%) | ||||
Oxygen | 7 (10%) | ||||
Vital signs | |||||
Systolic Blood Pressure [mmHg] | 71 | 114.3 ± 12.90 | 111.2 | 117.3 | 110 [105; 123] |
Diastolic Blood Pressure [mmHg] | 71 | 72.0 ± 9.93 | 69.6 | 74.3 | 70 [65; 80] |
Heart Rate [bpm] | 71 | 80.6 ± 9.99 | 78.2 | 83.0 | 80 [72; 88] |
Clinical parameters | |||||
NTproBNP [pmol/L] | 41 | 140.97 ± 230.87 | 68.10 | 213.84 | 43.3 [18.1; 175.5] |
6-min walking distance [meters] | 68 | 359.0 ± 91.48 | 336.9 | 381.1 | 359 [295; 419] |
Hemodynamics measured by right heart catheter | |||||
mean PAP [mmHg] | 45 | 46.13 ± 9.833 | 43.17 | 49.08 | 46.0 [39; 54] |
Pulmonary Vascular Resistance [dyn*sec*cm−5] | 45 | 700.75 ± 282.82 | 615.79 | 785.72 | 593.6 [510.6; 829] |
Cardiac Index [L/min/m2] | 45 | 2.53 ± 0.46 | 2.39 | 2.66 | 2.58 [2.31; 2.78] |
Cardiac Output [L/min] | 45 | 4.69 ± 1.06 | 4.37 | 5.01 | 4.6 [4.3; 5.2] |
Pulmonary Arterial Wedge Pressure [mmHg] | 45 | 7.4 ± 2.85 | 6.5 | 8.2 | 7 [5; 8] |
Effect of riociguat on right heart size and function
baseline - 3 months | baseline - 6 months | 12 months | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Mean ± standard deviation | 95% CI (mean) | median and interquartile ranges | Mean ± standard deviation | 95% CI (mean) | median and interquartile ranges | Mean ± standard deviation | 95% CI (mean) | median and interquartile ranges | ||||||||||
N | lower limit | upper limit | p-value | N | lower limit | upper limit | p-value | N | lower limit | upper limit | p-value | |||||||
RA area [cm2] | 30 | - 1.21 ± 3.94 | - 2.67 | 0.26 | 1.0 [−4.54; 1.69] | 0.104 | 34 | - 2.43 ± 3.74 | - 3.73 | - 1.13 | 1.99 [−5.0; 0.29] | < 0.001 | 49 | - 2.58 ± 4.37 | - 3.84 | - 1.33 | 2.38 [−6.0; 0.3] | < 0.001 |
RV area [cm2] | 29 | -3.0 ± 2.95 | −4.12 | −1.87 | 2.0 [−5.0; − 1.0] | < 0.001 | 32 | −3.01 ± 3.15 | −4.23 | −1.96 | −2.36 [−5.5; − 1.0] | < 0.001 | 44 | - 3.51 ± 5.23 | −5.1 | − 1.92 | − 3.25 [− 5.6; 0.0] | < 0.001 |
TAPSE [mm] | 29 | 0.86 ± 2.97 | - 0.27 | 1.99 | 0 [−1.0; 2.0] | 0.257 | 32 | 2.38 ± 4.25 | 0.85 | 3.92 | 2.0 [0; 3.7] | 0.003 | 45 | 2.95 ± 4.78 | 1.52 | 4.39 | 3.7 [0; 5.5] | < 0.001 |
FAC [mm] | 15 | 1.67 ± 3.18 | −0.09 | 3.43 | 0.99 [0; 2.41] | 0.068 | 16 | 6.13 ± 4.32 | 3.83 | 8.43 | 5.11 [3.69; 8.33] | < 0.001 | 27 | 8.12 ± 8.87 | 4.61 | 11.62 | 8.72 [−3.2; 15.0] | < 0.001 |
RV thickness [mm] | 28 | −0.68 ± 1.99 | −1.45 | 0.1 | 0.0 [0.0; 1.75] | 0.109 | 27 | −1.13 ± 2.03 | −1.94 | −0.33 | 1.0 [0.0; 2.0] | 0.008 | 32 | −0.76 ± 2.2 | −1.55 | 0.03 | 0.9 [0.0; 2.0] | 0.023 |
TRV [cm/sec] | 29 | - 0.28 ± 0.5 | −0.47 | −0.09 | −0.24 [− 0.4;-0.02] | 0.005 | 32 | − 0.48 ± 0.63 | −0.71 | − 0.25 | −0.57 [− 0.71; − 0.07] | < 0.001 | 47 | −0.36 ± 0.83 | −0.6 | −0.12 | − 0.52 [− 0.77; − 0.03] | 0.005 |
IVC diameter [mm] | 22 | −0.81 ± 3.48 | −2.35 | 0.73 | 0.5 [−2.0; 0.0] | 0.288 | 25 | −0.23 ± 3.83 | −1.81 | 1.35 | 0.0 [− 2.0; 3.0] | 0.764 | 28 | −0.50 ± 4.07 | −2.08 | 1.08 | 1.0 [−3.45; 2.6] | 0.518 |
LV-EI | 27 | −0.05 ± 0.17 | −0.12 | 0.02 | 0.0 [−0.1; 0.0] | 0.147 | 30 | −0.005 ± 0.25 | −0.1 | 0.09 | 0.0 [−0.2; 0.1] | 0.906 | 40 | −0.13 ± 0.22 | −0.20 | −0.06 | − 0.1 [− 0.25; 00] | < 0.001 |
PA diameter [mm] | 21 | − 0.05 ± 2.09 | −1.0 | 0.9 | 0.0 [−1.0; 0.0] | 0.886 | 21 | −0.99 ± 4.35 | −2.97 | 0.99 | 0.0 [−2.0; 0.7] | 0.309 | 26 | −1.64 ± 3.17 | −2.92 | 0.36 | −1.0 [−3.5; 0.0] | 0.014 |
Description of patients who did not receive echocardiography after 12 months
Variable | 12 months dropouts [n = 21] | 12 months completers [n = 50] | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Mean ± standard deviation or n and (%) | 95% CI (mean) | median and interquartile ranges | Mean ± standard deviation or n and % | 95% CI (mean) | median and interquartile ranges | ||||||
N | lower limit | upper limit | N | lower limit | upper limit | p-value | |||||
Demographics | |||||||||||
Age [years] | 21 | 59.5 ± 11.66 | 54.2 | 64.8 | 56 [49; 71] | 50 | 59.0 ± 14.2 | 54.9 | 63.0 | 60 [51; 71] | 0.845 |
Height [cm] | 21 | 170.1 ± 10.95 | 165.1 | 175.1 | 172 [163; 175] | 50 | 166.5 ± 9.3 | 163.9 | 169.2 | 168 [160; 173] | 0.267 |
Weight [kg] | 21 | 78.7 ± 12.5 | 73.0 | 84.4 | 75.0 [71; 88] | 50 | 76.2 ± 19.3 | 70.7 | 81.6 | 71 [65; 85] | 0.196 |
BMI [kg/m2] | 21 | 27.2 ± 3.5 | 25.6 | 28.8 | 26.8 [25.7; 28.4] | 50 | 27.3 ± 5.6 | 25.7 | 28.9 | 26.0 [23.3; 30.0] | 0.575 |
gender [female n (%)] | 11 (52.4%) | 27 (54.0%) | |||||||||
Pulmonary hypertension etiology | |||||||||||
Idiopathic PAH | 3 (14.3%) | 11 (22.0%) | |||||||||
Other PAH | 6 (28.6%) | 12 (24.0%) | |||||||||
Chronic thromboembolic pulmonary hypertension | 12 (57.1%) | 27 (54.0%) | |||||||||
WHO functional class | |||||||||||
II | 6 (28.6%) | 11 (22.0%) | |||||||||
III | 15 (71.4%) | 39 (78.0%) | |||||||||
Pulmonary hypertension targeted treatment | |||||||||||
treatment naÏve | 2 (33.3%) | 35 (70%) | |||||||||
Endothelin-Receptor-Antagonist | 2 (33.3%) | 12 (24%) | |||||||||
Phosphodiesterase-5-inhibitor | 2 (33.3%) | 3 (6%) | |||||||||
Oxygen | 2 (33.3%) | 5 (10%) | |||||||||
Vital signs | |||||||||||
Systolic Blood Pressure [mmHg] | 21 | 116 ± 12 | 110 | 121 | 110 [110; 125] | 50 | 114 ± 14 | 110 | 121 | 110 [110; 125] | 0.378 |
Diastolic Blood Pressure [mmHg] | 21 | 75 ± 10 | 71 | 80 | 76 [70; 80] | 50 | 71 ± 10 | 68 | 73 | 70 [64; 80] | 0.040 |
Heart Rate [bpm] | 21 | 79 ± 9 | 75 | 83 | 80 [72; 84] | 50 | 81 ± 11 | 78 | 84 | 80 [73; 88] | 0.645 |
Clinical parameters | |||||||||||
NTproBNP [pmol/L] | 11 | 183.7 ± 243.4 | 20.2 | 347.2 | 76 [29.6; 217.4] | 30 | 125.3 ± 228.4 | 40.0 | 210.6 | 42.2 [17.4; 144.8] | 0.471 |
6-min walking distance [meters] | 18 | 338.5 ± 99.9 | 288.8 | 388.2 | 362 [270; 406] | 50 | 366.4 ± 88.1 | 341.3 | 391.4 | 370 [301; 420] | 0.440 |
Hemodynamics measured by right heart catheter | |||||||||||
mean PAP [mmHg] | 13 | 48.6 ± 54.1 | 43.0 | 54.1 | 47 [45; 57] | 32 | 45.1 ± 10.1 | 41.5 | 48.8 | 43.5 [37.8; 53.3] | 0.215 |
Pulmonary Vascular Resistance [dyn*sec*cm− 5] | 13 | 781.3 ± 259.3 | 624.6 | 938.0 | 747.8 [615.4; 904.3] | 32 | 668.0 ± 289.3 | 563.8 | 772.3 | 563.1 [495.2; 789.7] | 0.112 |
Cardiac Index [L/min/m2] | 13 | 2.4 ± 0.5 | 2.1 | 2.7 | 2.5 [2.2; 2.7] | 32 | 2.6 ± 0.5 | 2.4 | 2.7 | 2.6 [2.4; 2.8] | 0.276 |
Cardiac Output [L/min] | 13 | 4.6 ± 0.9 | 4.0 | 5.1 | 4.6 [4.3; 5.2] | 32 | 4.8 ± 1.1 | 4.3 | 5.2 | 4.6 [4.3; 8.2] | 0.861 |
Pulmonary Arterial Wedge Pressure [mmHg] | 13 | 6.0 ± 2.7 | 4.4 | 7.6 | 6 [5; 8] | 32 | 7.9 ± 2.8 | 6.9 | 8.9 | 7 [6; 10] | 0.052 |
Placebo group
Mean ± standard deviation | 95% CI (mean) | median and interquartile ranges | |||
---|---|---|---|---|---|
Parameter | N | lower limit | upper limit | ||
Echocardiography | |||||
right atrial area [cm2] | 5 | −0.4 ± 2.9 | −4.1 | 3.2 | 1 [−3.2; 2] |
right ventricular area [cm2] | 5 | 2.0 ± 6.4 | −6.0 | 9.8 | 0 [−5.3; 10] |
TAPSE [mm] | 5 | 0.5 ± 3.3 | −3.6 | 4.5 | 0 [−2.6; 6] |
RV thickness [mm] | 4 | 1.0 ± 0.8 | −0.3 | 2.3 | 1.0 [0.5; 1.5] |
TRV [cm/sec] | 4 | 0.1 ± 0.2 | −0.3 | 0.4 | 0.1 [−0.1; 0.3] |
IVC diameter [mm] | 5 | −0.4 ± 2.7 | −3.8 | 2.9 | 0 [0; 0.8] |
LV-EI | 5 | −0.1 ± 0.1 | −0.2 | 0.03 | −0.1 [− 0.2; 0] |
PA diameter [mm] | 4 | −0.25 ± 1.3 | −2.3 | 1.8 | 0 [−1.0; 0.5] |