Nitric Oxide Stroke Volume Index as a New Hemodynamic Prognostic Parameter for Patients with Pulmonary Arterial Hypertension
Abstract
:1. Introduction
2. Methods
Study Population
3. Clinical Assessments
3.1. Echocardiography
3.2. Biochemical Methods
3.3. Right Heart Catheterization
4. Protocol of Vasoreactivity Testing
5. Data Analysis
Statistical Analysis
6. Results
6.1. Univariable Cox Regression Analysis
6.2. Multivariable Cox Regression Analysis with a Step-Wise Algorithm—Selection of Variables for Analysis and Results
7. Discussion
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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All Group N (%) Mean ± SD Median (IQR) n = 62 | A 5-Years Survival N (%) Mean ± SD Median (IQR) n = 25 | B Death or Lung Transplantation Mean ± SD Median (IQR) n = 37 | A vs. B “U” Mann-Whitney, t-Student, Ch2 Tests p | |
---|---|---|---|---|
General characteristic | ||||
Female—n (%) | 53 (85.48) | 23 (92.00) | 30 (81.08) | p = 0.407 |
age (years) (18.11–74.87) (median (IQR)) | 46.84 (33.33–58.02) | 46.88 (27.00–52.89) | 46.80 (33.56–59.28) | p = 0.239 |
Time of follow-up (days) (7–1825) | 1089.92 ± 703.00 | 1825.00 | 593.24 ± 456.77 | p = 0.226 |
WHO-FC I-II—n (%) | 12 (19.35) | 10 (40.00) | 2 (5.41) | p = 0.002 |
WHO-FC III-IV—n (%) | 50 (80.65) | 15 (60.00) | 35 (94.59) | p = 0.002 |
NO test responder—n (%) | 8 (12.90) | 6 (24.00) | 2 (5.41) | p = 0.079 |
6MWT (m) | 318.84 ± 136.64 | 395.06 ± 132.42 | 265.92 ± 113.81 | p < 0.001 |
PAH etiology | ||||
Idiopathic—n (%) | 49 (79.03) | 23 (92.00) | 26 (70.27) | p = 0.081 |
Heritable—n (%) | 3 (4.84) | 0 (0.00) | 3 (8.12) | p = 0.392 |
Connective tissue disease—n (%) | 7 (11.29) | 2 (8.00) | 5 (13.51) | p = 0.792 |
Human immunodeficiency virus infection—n (%) | 1 (1.61) | 0 (0.00) | 1 (2.70) | p = 0.842 |
Congenital heart disease (corrected)—n (%) | 2 (3.23) | 1 (4.00) | 1 (2.70) | p = 0.653 |
Pharmacotherapy | ||||
CCB—n (%) (monotherapy—n (%)) | 39 (62.90) (22 (35.48)) | 15 (60.00) (8 (32.00)) | 24 (64.86) (14 (37.84)) | p = 0.904 |
PDE-5i—n (%) (monotherapy—n (%)) | 39 (62.90) 19 (30.65) | 17 (68.00) 10 (40.00) | 22 (59.46) 9 (24.32) | p = 0.302 |
Prostanoids *—n (%) (monotherapy—n (%)) | 18 (29.03) (1 (1.61)) | 5 (20.00) (0 (0.00)) | 13 (35.14) (1 (2.70)) | p = 0.316 |
ERA—n (%) (monotherapy—n (%)) | 5 (8.06) (0 (0.00)) | 4 (16.00) (0 (0.00)) | 1 (2.70) (0 (0.00)) | p = 0.206 |
PDE-5i + prostanoids—n (%) | 15 (24.19) | 3 (12.00) | 12 (37.83) | p = 0.124 |
PDE-5i + ERA—n (%) | 3 (4.84) | 2 (8.00) | 1 (2.70) | p = 0.753 |
PDE-5i + prostanoids + ERA—n (%) | 2 (3.23) | 2 (8.00) | 0 (0.00) | |
Basic biochemistry | ||||
NT-proBNP ** (pg/mL) (n = 38) | 1828.0 (2020.0–3270.0) | 2020.0 (880.0–2656.0) | 2253.0 (1726.0–3645.0) | p = 0.001 |
Uric acid ** (µmol/L) (n = 46) | 393.00 (303.00–536.00) | 307.00 (273.00–360.00) | 474.00 (393.00–570.00) | p = 0.003 |
Haemoglobin (g/dL) | 13.85 (12.60–14.90) | 13.90 (12.90–14.60) | 13.80 (12.30–14.90) | p = 0.649 |
Sodium (mmol/L) | 139.00 (136.00–142.00) | 140.60 (137.00–143.00) | 138.00 (136.00–141.00) | p = 0.046 |
Creatinine (µmol/L) | 81.65 (66.80–99.00) | 66.80 (61.40–79.20) | 90.00 (78.00–106.40) | p = 0.001 |
Echocardiographic data | ||||
RVd (4 chamber view) (mm) | 43.10 ± 10.57 | 39.29 ± 11.22 | 45.57 ± 9.48 | p = 0.022 |
RAA (cm2) | 23.15 ± 8.19 | 18.54 ± 6.86 | 26.31 ± 7.57 | p < 0.001 |
TAPSE ** (mm) (n = 36) | 17.42 ± 5.90 | 18.95 ± 5.89 | 15.71 ± 5.58 | p = 0.100 |
TR V max. (m/s) | 4.17 ± 2.71 | 3.79 ± 2.81 | 4.41 ± 2.48 | p = 0.006 |
RVSP (mmHg) | 78.44 ± 29.57 | 64.60 ± 31.77 | 87.78 ± 24.58 | p = 0.001 |
AcT ** (ms) (n = 58) | 65.34 ± 24.77 | 77.39 ± 27.73 | 57.43 ± 19.20 | p = 0.648 |
Fluid in pericardium—n (%) | 18 (29.03) | 4 (14.29) | 14 (37.84) | p = 0.116 |
VCI ** diameter (mm) (n = 53) | 19.00 (16.50–22.50) | 18.00 (15.00–21.00) | 20.00 (17.00–23.00) | p = 0.102 |
VCI **collapse during inspiration—N1/N2 (%) | 15/38 (28.30) | 11/11 (100.00) | 4/27 (14.80) | p = 0.004 |
Basic Measurements Mean ± SD Median (IQR) | iNO Inhalation (60 ppm) Mean ± SD Median (IQR) | Wilcoxon Test, Paired t-Student Test p | |
---|---|---|---|
PAPs (mmHg) | 80.10 (64.00–99.50) | 65.00 (54.00–83.50) | p < 0.001 |
PAPd (mmHg) | 38.10 (31.00–48.00) | 33.50 (24.20–39.10) | p < 0.001 |
PAPm (mmHg) | 52.57 (41.67–62.00) | 44.00 (33.60–53.50) | p < 0.001 |
SBP (mmHg) | 122.67 ± 18.53 | 120.79 ± 17.70 | p = 0.023 |
DBP (mmHg) | 75.89 ± 12.18 | 73.57 ± 12.05 | p = 0.013 |
MBP (mmHg) | 91.48 ± 12.98 | 89.44 ± 12.54 | p < 0.007 |
HR (bpm) | 81.67 ± 14.71 | 76.75 ± 14.20 | p < 0.001 |
SVI (mL/m2) | 27.09 (20.71–34.69) | 28.61 (22.62–56.48) | p = 0.058 |
PAWP (mmHg) | 10.00 (6.70–11.00) | 9.58 (6.08–11.75) | p = 0.433 |
PVRI (Wood units × m2) | 19.52 (14.73–29.97) | 15.76 (10.85–26.59) | p < 0.001 |
TPG (mmHg) | 43.75 (34.77–55.33) | 31.90 (22.41–39.40) | p < 0.001 |
RAP (mmHg) | 8.00 (5.00–12.00) | 7.50 (4.00–11.00) | p < 0.001 |
CI (L/min/m2) | 2.17 (1.70–2.88) | 2.24 (1.86–2.88) | p = 0.791 |
Basic Hemodynamic Parameters | iNO Inhalation Hemodynamic Parameters | |||||||
---|---|---|---|---|---|---|---|---|
5-Years Survival Mean ± SD Median (IQR) n = 25 | Death or Lung Transplantation Mean ± SD Median (IQR) n = 37 | Mann-Whitney U, t-Student, Tests p | 5-Years Survival Mean ± SD n = 25 | Death or Lung Transplantation Mean ± SD n = 37 | Mann-Whitney U, t-Student, Tests p | Wilcoxon Test, Paired t-Student Test p | Wilcoxon Test, Paired t-Student Test p | |
A | B | A vs B | C | D | C vs D | A vs C | B vs D | |
PAPs (mmHg) | 85.00 (62.00–99.50) | 80.00 (65.80–98.00) | p = 0.763 | 60.00 (41.25–83.00) | 68.40 (57.00–90.00) | p = 0.146 | p = 0.001 | p = 0.001 |
PAPd (mmHg) | 37.60 (26.00–48.00) | 38.20 (33.00–43.00) | p = 0.651 | 29.80 (21.00–39.00) | 33.80 (26.00–39.20) | p = 0.290 | p = 0.001 | p = 0.001 |
PAPm (mmHg) | 55.00 (38.00–62.33) | 51.87 (44.33–60.00) | p = 0.774 | 41.17 (27.27–52.67) | 45.33 (39.07–55.00) | p = 0.202 | p = 0.001 | p = 0.001 |
SBP (mmHg) | 124.22 ± 16.02 | 121.62 ± 20.19 | p = 0.592 | 120.77 ± 16.45 | 120.80 ± 18.78 | p = 0.994 | p = 0.080 | p = 0.157 |
DBP (mmHg) | 74.91 ± 14.24 | 76.55 ± 10.74 | p = 0.606 | 72.21 ± 12.61 | 74.54 ± 11.72 | p = 0.465 | p = 0.093 | p = 0.072 |
MBP (mmHg) | 91.34 ± 13.86 | 91.56 ± 12.54 | p = 0.948 | 88.40 ± 12.57 | 90.21 ± 12.65 | p = 0.588 | p = 0.049 | p = 0.069 |
HR (bpm) | 76.04 ± 16.07 | 85.47 ± 12.55 | p = 0.012 | 71.66 ± 14.32 | 80.39 ± 13.13 | p = 0.017 | p = 0.035 | p < 0.001 |
SVI (mL/m2) | 34.69 (25.92–46.88) | 21.41 (19.52–29.07) | p < 0.001 | 65.62 (49.20–76.40) | 24.41 (17.99–28.27) | p < 0.001 | p = 0.001 | p = 0.308 |
PAWP (mmHg) | 9.00 (5.00–11.00) | 10.00 (8.00–11.00) | p = 0.312 | 8.00 (5.00–12.00) | 10.00 (7.00–11.50) | p = 0.368 | p = 0.374 | p = 0.846 |
PVRI (Wood units × m2) | 16.42 (10.93–27.24) | 24.52 (15.68–29.97) | p = 0.164 | 12.13 (7.10–21.11) | 18.12 (12.74–27.28) | p = 0.070 | p = 0.001 | p = 0.001 |
TPG (mmHg) | 47.33 (31.22–55.33) | 41.87 (37.03–52.00) | p = 0.949 | 32.77 (19.67–45.67) | 37.13 (30.07–45.00) | p = 0.286 | p = 0.001 | p = 0.001 |
RAP (mmHg) | 7.00 (3.70–13.00) | 8.00 (7.00–10.00) | p = 0.518 | 6.00 (3.00–12.00) | 8.00 (6.00–10.00) | p = 0.323 | p = 0.004 | p = 0.019 |
CI (L/min/m2) | 2.69 (2.02–3.13) | 1.98 (1.63–2.50) | p = 0.007 | 2.48 (2.21–3.07) | 2.14 (1.72–2.44) | p = 0.006 | p = 0.903 | p = 0.397 |
SaO2 (%) | 94.40 (92.00–97.00) | 92.00 (89.00–93.40) | p = 0.008 | |||||
SvO2 (%) | 69.00 (65.00–75.00) | 64.50 (58.00–71.00) | p = 0.014 |
HR | 95% Confidence Interval | p | |
---|---|---|---|
Female (yes/no) | 0.507 | 0.222–1.157 | 0.107 |
Age (years) | 1.012 | 0.990–1.035 | 0.292 |
WHO–FC (by one class) | 2.408 | 1.458–3.978 | 0.001 |
NO test responder (yes/no) | 0.258 | 0.062–1.076 | 0.063 |
6MWT distance (1 m) | 0.995 | 0.992–0.997 | <0.001 |
PAH Idiopathic (yes /no) | 1.049 | 0.495–2.225 | 0.900 |
PAH Connective tissue disease (yes/no) | 1.327 | 0.552–3.188 | 0.527 |
CCB (only) (yes/no) | 1.139 | 0.580–2.239 | 0.705 |
PDE-5i (only) (yes/no) | 0.783 | 0.406–1.510 | 0.465 |
PDE-5i + prostanoids(yes/no) | 1.379 | 0.701–2.715 | 0.352 |
PDE-5i + ERA(yes/no) | 0.232 | 0.032–1.692 | 0.15 |
NT-proBNP (by 100 pg/mL) | 1.012 | 1.005–1.019 | <0.001 |
Uric acid (by 10 µmol/L) | 1.031 | 1.013–1.048 | <0.001 |
Haemoglobin (by 1 g/dL) | 0.921 | 0.779–1.088 | 0.331 |
Sodium (by 1 mmol/L) | 0.927 | 0.852–1.008 | 0.075 |
Creatinine (by 1 µmol/L) | 1.018 | 1.006–1.030 | 0.002 |
RVd (4 chamber view) (by 1 mm) | 1.028 | 1.001–1.055 | 0.041 |
RAA (by 1 cm2) | 1.07 | 1.032–1.110 | <0.001 |
TAPSE (by 1 mm) | 0.922 | 0.922–0.922 | 0.922 |
TR V max. (by 1 m/s) | 1.924 | 1.274–2.906 | 0.002 |
RVSP (by 1 mmHg) | 1.017 | 1.006–1.029 | 0.002 |
AcT (by 1 ms) | 0.976 | 0.961–0.992 | 0.003 |
Fluid in pericardium (yes/no) | 1.986 | 1.018–3.874 | 0.044 |
VCI diameter (1 mm) (n = 53) | 0.994 | 0.964–1.026 | 0.729 |
VCI collapse during inspiration (yes/no) | 0.258 | 0.090–0.740 | 0.012 |
HR | 95% Confidence Interval | p | |
---|---|---|---|
PAPs (mmHg) | 1.001 | 0.989–1.013 | 0.877 |
PAPd (mmHg) | 1.007 | 0.986–1.028 | 0.523 |
PAPm (mmHg) | 1.004 | 0.986–1.021 | 0.681 |
SBP (mmHg) | 0.991 | 0.972–1.009 | 0.318 |
DBP (mmHg) | 1.004 | 0.979–1.029 | 0.778 |
MBP (mmHg) | 0.997 | 0.972–1.021 | 0.787 |
HR (bpm) | 1.030 | 1.009–1.052 | 0.006 |
SVI (mL/m2) | 0.939 | 0.907–0.971 | <0.001 |
PAWP (mmHg) | 1.058 | 0.970–1.155 | 0.201 |
PVRI (Wood units × m2) | 1.017 | 0.990–1.044 | 0.220 |
TPG (mmHg) | 1.001 | 0.983–1.020 | 0.893 |
RAP (mmHg) | 1.003 | 0.949–1.060 | 0.910 |
CI (L/min/m2) | 0.500 | 0.300–0.834 | 0.008 |
SaO2 (%) | 0.874 | 0.818–0.934 | <0.001 |
SvO2 (%) | 0.970 | 0.945–0.996 | 0.024 |
HR | 95% Confidence Interval | p | |
---|---|---|---|
PAPs (mmHg) | 1.005 | 0.995–1.016 | 0.349 |
PAPd (mmHg) | 1.010 | 0.990–1.031 | 0.340 |
PAPm (mmHg) | 1.008 | 0.992–1.024 | 0.334 |
SBP (mmHg) | 0.997 | 0.977–1.017 | 0.740 |
DBP (mmHg) | 1.006 | 0.980–1.033 | 0.643 |
MBP (mmHg) | 1.003 | 0.976–1.030 | 0.849 |
HR (bpm) | 1.033 | 1.009–1.057 | 0.006 |
SVI (mL/m2) | 0.913 | 0.883–0.945 | <0.001 |
PAWP (mmHg) | 1.065 | 0.985–1.151 | 0.113 |
PVRI (Wood units × m2) | 1.023 | 0.995–1.052 | 0.114 |
TPG (mmHg) | 1.010 | 0.982–1.039 | 0.496 |
RAP (mmHg) | 1.009 | 0.953–1.069 | 0.750 |
CI (L/min/m2) | 0.467 | 0.266–0.818 | 0.008 |
AUC | 95% Confidence Interval | p | Cut Off Value | Specificity/Sensitivity (%) | |
---|---|---|---|---|---|
HR(baseline) | 0.682 | 0.540–0.823 | 0.0118 | 79.6bpm | 72.97/64.00 |
CI(baseline) | 0.704 | 0.568–0.839 | 0.0032 | 2.471 L/min/m2 | 72.97/64.00 |
SVI(baseline) | 0.773 | 0.646–0.900 | <0.0001 | 29.142 mL/m2 | 74.48/72.44 |
SaO2 | 0.699 | 0.568–0.831 | 0.0030 | 95.20% | 85.78/48.00 |
RAA | 0.784 | 0.661–0.907 | <0.0001 | 17.00 cm2 | 94.29/58.33 |
HR(NO test) | 0.674 | 0.530–0.817 | 0.0178 | 76.75 bpm | 68.57/72.00 |
CI(NO test) | 0.71 | 0.576–0.844 | 0.0021 | 2.372 L/min/m2 | 75.00/64.00 |
SVI(NO test) | 0.956 | 0.899–1.000 | <0.0001 | 39.86 mL/m2 | 100.0/84.00 |
HR | 95% Confidence Interval | p | |
---|---|---|---|
SVI(NO test) (mL/m2) | 0.910 | 0.878–0.944 | <0.001 |
SaO2 (1%) | 0.910 | 0.843–0.982 | 0.015 |
HR | 95% Confidence Interval | p | |
---|---|---|---|
SVI(NO test) (mL/m2) | 0.917 | 0.876–0.960 | <0.001 |
SaO2 (1%) | 0.909 | 0.795–1.040 | 0.166 |
NT-proBNP (pg/mL) (n = 38) | 1.008 | 1.000–1.016 | 0.063 |
SVI(NO test) (mL/m2) | 0.903 | 0.864–0.945 | <0.001 |
SaO2 (1%) | 0.896 | 0.810–0.990 | 0.031 |
Uric acid (µmol/L) (n = 46) | 1.013 | 0.992–1.035 | 0.227 |
SVI(NO test) (mL/m2) | 0.911 | 0.878–0.946 | <0.001 |
SaO2 (1 pp) | 0.911 | 0.843–0.984 | 0.0175 |
Sodium (mmol/L) (n = 62) | 0.983 | 0.906–1.066 | 0.679 |
SVI(NO test) (mL/m2) | 0.910 | 0.877–0.945 | <0.001 |
SaO2 (1%) | 0.903 | 0.836–0.976 | 0.010 |
AcT (ms) (n = 58) | 0.991 | 0.974–1.008 | 0.275 |
SVI(NO test) (mL/m2) (n = 53) | 0.901 | 0.862–0.943 | <0.001 |
SaO2 (1%) | 0.904 | 0.831–0.984 | 0.019 |
VCI collapse during inspiration (n = 53) | 2.279 | 0.660–7.869 | 0.193 |
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Barańska-Pawełczak, K.; Wojciechowska, C.; Opara, M.; Jacheć, W. Nitric Oxide Stroke Volume Index as a New Hemodynamic Prognostic Parameter for Patients with Pulmonary Arterial Hypertension. J. Clin. Med. 2020, 9, 2939. https://doi.org/10.3390/jcm9092939
Barańska-Pawełczak K, Wojciechowska C, Opara M, Jacheć W. Nitric Oxide Stroke Volume Index as a New Hemodynamic Prognostic Parameter for Patients with Pulmonary Arterial Hypertension. Journal of Clinical Medicine. 2020; 9(9):2939. https://doi.org/10.3390/jcm9092939
Chicago/Turabian StyleBarańska-Pawełczak, Karolina, Celina Wojciechowska, Mariusz Opara, and Wojciech Jacheć. 2020. "Nitric Oxide Stroke Volume Index as a New Hemodynamic Prognostic Parameter for Patients with Pulmonary Arterial Hypertension" Journal of Clinical Medicine 9, no. 9: 2939. https://doi.org/10.3390/jcm9092939