Conundrum of Classifying Subtypes of Pulmonary Hypertension—Introducing a Novel Approach to Classify “Borderline” Patients in a Population with Severe Aortic Stenosis Undergoing TAVI
Abstract
:1. Introduction
2. Methods
2.1. Patient Population
2.2. Procedure of RHC
2.3. Subtypes of PH
2.4. Transthoracic Echocardiography
2.5. TAVI Procedure
2.6. Clinical Follow-Up and Study Endpoint
2.7. Statistical Analysis
3. Results
3.1. PH Subtypes of Study Collective
3.2. General Characteristics
3.3. Kaplan–Meier Curves and Cox Proportional Hazard Regression
3.4. ROC Curves and Cut-Off Values
4. Discussion
4.1. PH as a Solitary Risk Factor in Patients Receiving TAVI?
4.2. Prec-PH and AS—Does This Constellation Fit Together?
4.3. Borderlinepc-PH—Is It Worth Being a New Subtype?
5. Conclusions
6. Limitations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Overall Cohort | No PH | Prec-PH | Ipc-PH | Borderlinepc-PH | Cpc-PH | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Mean | SD (±) | Mean | SD (±) | Mean | SD (±) | Mean | SD (±) | Mean | SD (±) | Mean | SD (±) | p-Value | |
General data | |||||||||||||
Age (years) | 80.5 | 7.2 | 80.6 | 6.2 | 83.5 | 5.6 | 79.6 | 8.1 | 80.6 | 7.1 | 80.6 | 7.4 | 0.234 |
Weight (kg) | 73.7 | 13.1 | 70.8 | 13.1 | 75.4 | 16.3 | 77.2 | 12.6 | 71.5 | 12.1 | 70.1 | 10.9 | 0.005 |
Height (cm) | 164.4 | 8.9 | 162.9 | 8.9 | 164.7 | 9.0 | 166.0 | 8.8 | 163.1 | 8.5 | 166.0 | 9.6 | 0.102 |
Creatinine (µmol/L) | 121.9 | 87.8 | 104.6 | 54.4 | 114.6 | 53.2 | 136.4 | 109.7 | 121.8 | 90.6 | 111.1 | 52.2 | 0.255 |
C-reactive protein (mg/L) | 18.9 | 32.8 | 10.8 | 22.1 | 15.5 | 19.8 | 19.6 | 34.3 | 26.2 | 41.5 | 19.5 | 27.4 | 0.132 |
Hemoglobin (mmol/L) | 7.5 | 1.1 | 7.5 | 1.0 | 7.7 | 0.9 | 7.2 | 1.1 | 7.5 | 1.2 | 7.7 | 1.4 | 0.218 |
STS-Score | 4.1 | 2.5 | 3.5 | 2.1 | 4.7 | 3.0 | 4.1 | 2.8 | 4.3 | 2.2 | 4.0 | 2.8 | 0.267 |
EuroScore II | 6.7 | 5.4 | 5.0 | 5.7 | 6.0 | 4.2 | 7.4 | 5.2 | 7.6 | 5.3 | 7.4 | 5.1 | 0.175 |
Concomitant diseases | |||||||||||||
Insulin-dependent diabetes (%) | 23.9 | 19.4 | 8.3 | 29.8 | 25.7 | 20.0 | 0.186 | ||||||
Non-insulin-dependent diabetes (%) | 34.5 | 35.8 | 50.0 | 25.0 | 36.5 | 60.0 | 0.024 | ||||||
Arterial hypertension (%) | 91.2 | 92.5 | 95.8 | 88.5 | 91.9 | 93.3 | 0.756 | ||||||
Coronary heart disease - 1 vessel (%) | 21.8 | 20.9 | 16.7 | 23.1 | 21.6 | 26.7 | 0.950 | ||||||
Coronary heart disease - 2 vessels (%) | 13.4 | 10.4 | 25.0 | 15.4 | 12.2 | 6.7 | 0.194 | ||||||
Coronary heart disease - 3 vessels (%) | 15.5 | 14.9 | 4.2 | 13.5 | 23.0 | 13.3 | 0.206 | ||||||
COPD (%) | 25.0 | 19.4 | 29.2 | 27.9 | 23.0 | 33.3 | 0.641 | ||||||
Myocardial infarction (%) | 14.8 | 14.9 | 4.2 | 17.5 | 14.9 | 13.3 | 0.599 | ||||||
Stroke (%) | 15.1 | 10.4 | 20.8 | 19.2 | 12.2 | 13.3 | 0.454 | ||||||
Atrial fibrillation (%) | 52.6 | 34.9 | 40.0 | 66.7 | 52.4 | 71.4 | 0.023 | ||||||
NYHA II | 11.3 | 17.9 | 20.8 | 8.7 | 5.4 | 13.3 | 0.072 | ||||||
NYHA III | 60.2 | 62.7 | 62.5 | 58.7 | 62.2 | 46.7 | 0.844 | ||||||
NYHA IV | 22.9 | 13.4 | 12.5 | 25.0 | 29.7 | 33.3 | 0.093 | ||||||
Echocardiographic measurements | |||||||||||||
EF (%) | 56.6 | 16.2 | 60.2 | 15.1 | 59.8 | 13.2 | 56.8 | 16.0 | 52.0 | 17.4 | 57.2 | 16.7 | 0.041 |
LVEDD (mm) | 48.9 | 8.0 | 47.2 | 7.9 | 48.1 | 7.3 | 49.9 | 7.5 | 49.5 | 8.4 | 49.3 | 9.9 | 0.284 |
LVESD (mm) | 32.5 | 9.5 | 30.0 | 9.3 | 32.6 | 9.6 | 33.0 | 9.3 | 33.9 | 9.5 | 34.8 | 11.6 | 0.286 |
sPAP (mmHg) | 41.8 | 13.4 | 32.6 | 7.7 | 34.3 | 11.6 | 44.0 | 12.1 | 47.0 | 14.7 | 50.3 | 13.5 | <0.001 |
AVA (cm2) | 0.7 | 0.2 | 0.7 | 0.2 | 0.6 | 0.2 | 0.7 | 0.2 | 0.6 | 0.2 | 0.7 | 0.2 | 0.012 |
AV max (m/s) | 4.3 | 0.7 | 4.5 | 0.7 | 4.4 | 0.5 | 4.3 | 0.6 | 4.2 | 0.8 | 4.4 | 0.8 | 0.243 |
AV dpmax (mmHg) | 78.5 | 26.3 | 82.8 | 25.6 | 79.4 | 15.5 | 75.1 | 23.0 | 78.2 | 32.3 | 81.1 | 30.2 | 0.470 |
AV dpmean (mmHg) | 47.7 | 16.7 | 50.6 | 17.5 | 48.2 | 12.5 | 45.6 | 14.2 | 47.6 | 19.9 | 48.0 | 17.9 | 0.481 |
Mitral regurgitation I° (%) | 49.6 | 63.6 | 62.5 | 45.5 | 32.4 | 66.7 | <0.001 | ||||||
Mitral regurgitation II° (%) | 38.4 | 31.8 | 16.7 | 41.4 | 48.6 | 20.0 | 0.042 | ||||||
Mitral regurgitation III° (%) | 8.4 | 3.1 | 16.7 | 9.1 | 14.9 | 6.7 | 0.076 | ||||||
Tricuspid regurgitation I° (%) | 51.9 | 61.3 | 45.8 | 48.4 | 48.6 | 33.3 | 0.284 | ||||||
Tricuspid regurgitation II° (%) | 32.7 | 30.6 | 29.2 | 32.3 | 29.7 | 46.7 | 0.791 | ||||||
Tricuspid regurgitation III° (%) | 12.3 | 3.2 | 20.8 | 17.1 | 16.2 | 13.3 | 0.028 | ||||||
Paravalvular regurgitation I° (%) | 37.9 | 38.1 | 60.0 | 39.6 | 30.0 | 37.5 | 0.524 | ||||||
Paravalvular regurgitation II° (%) | 13.1 | 11.9 | 10.0 | 15.1 | 10.0 | 25.0 | 0.798 | ||||||
Paravalvular regurgitation III° (%) | 0.7 | 0.0 | 10.0 | 0.0 | 0.0 | 0.0 | 0.006 | ||||||
Measurements of RHC | |||||||||||||
sPAP (mmHg) | 53.5 | 18.1 | 33.8 | 6.8 | 44.3 | 7.5 | 55.9 | 14.1 | 67.1 | 14.2 | 72.4 | 19.8 | <0.001 |
mPAP (mmHg) | 34.1 | 12.0 | 19.6 | 3.7 | 27.6 | 2.9 | 36.3 | 8.2 | 42.9 | 8.7 | 50.1 | 11.3 | <0.001 |
dPAP (mmHg) | 20.1 | 8.8 | 9.9 | 4.1 | 16.5 | 2.6 | 22.2 | 6.8 | 24.7 | 6.7 | 33.5 | 7.8 | <0.001 |
mPCWP (mmHg) | 21.3 | 9.4 | 10.6 | 4.0 | 12.9 | 1.8 | 25.5 | 7.5 | 27.1 | 6.9 | 23.7 | 7.5 | <0.001 |
DPG (mmHg) | −1.2 | 5.7 | −0.7 | 4.8 | 3.6 | 2.7 | −3.4 | 4.4 | −2.4 | 5.5 | 10.1 | 3.3 | <0.001 |
PVR (WU) | 3.3 | 2.1 | 2.5 | 1.5 | 3.2 | 1.0 | 1.9 | 0.6 | 5.0 | 2.2 | 6.7 | 2.3 | <0.001 |
TPG (mmHg) | 12.8 | 6.1 | 8.9 | 3.3 | 14.8 | 2.9 | 10.8 | 3.6 | 15.8 | 5.6 | 27.0 | 9.1 | <0.001 |
CO (L/min) | 4.2 | 1.2 | 4.2 | 1.3 | 4.2 | 1.0 | 4.5 | 1.2 | 3.7 | 1.0 | 3.9 | 1.0 | <0.001 |
Procedurale data | |||||||||||||
Transfemoral approach (%) | 75.4 | 77.6 | 83.3 | 72.1 | 77.0 | 66.7 | 0.678 | ||||||
CoreValve (%) | 22.3 | 17.9 | 29.2 | 25.0 | 21.6 | 20.0 | 0.800 | ||||||
JenaValve (%) | 15.9 | 16.4 | 12.5 | 15.4 | 16.2 | 20.0 | 0.979 | ||||||
Edwards (%) | 61.8 | 65.7 | 58.3 | 59.6 | 62.2 | 60.0 | 0.941 | ||||||
Major vascular complications (%) | 11.3 | 11.9 | 8.3 | 9.6 | 12.2 | 20.0 | 0.786 |
Univariate | Multivariable | |||
---|---|---|---|---|
Hazard Ratio (95% CI) | p-Value | Hazard Ratio (95% CI) | p-Value | |
General data | ||||
Age (years) | 0.998 (0.967–1.030) | 0.894 | ||
Weight (kg) | 0.989 (0.972–1.007) | 0.216 | ||
Height (cm) | 1.000 (0.974–1.025) | 0.974 | ||
Creatinine (µmol/L) | 1.001 (0.999–1.003) | 0.247 | ||
C-reactive protein (mg/L) | 1.006 (1.000–1.011) | 0.039 | 1.000 (0.984–1.016) | 0.968 |
Hemoglobin (mmol/L) | 0.899 (0.720–1.124) | 0.351 | ||
STS-Score | 1.164 (1.093–1.240) | <0.001 | 1.114 (0.951–1.306) | 0.181 |
EuroScore II | 1.081 (1.041–1.123) | <0.001 | 1.138 (1.049–1.235) | 0.002 |
Concomitant diseases | ||||
Insulin-dependent diabetes | 1.392 (0.854–2.268) | 0.184 | ||
Non-insulin-dependent diabetes | 1.366 (0.866–2.155) | 0.179 | ||
Arterial hypertension | 1.417 (0.572–3.508) | 0.451 | ||
Coronary heart disease ≥ 2 vessels | 1.354 (0.844–2.171) | 0.209 | ||
COPD | 1.939 (1.218–3.085) | 0.005 | 1.207 (0.380–3.836) | 0.750 |
Myocardial infarction | 1.782 (1.040–3.054) | 0.036 | 1.202 (0.305–4.730) | 0.792 |
Stroke | 1.959 (1.166–3.291) | 0.011 | 0.367 (0.079–1.718) | 0.203 |
Atrial fibrillation | 1.619 (0.869–3.019) | 0.129 | ||
NYHA ≥ III | 1.951 (0.786–4.843) | 0.150 | ||
Echocardiographic measurements | ||||
EF (%) | 0.990 (0.976–1.003) | 0.135 | ||
LVEDD (mm) | 1.015 (0.988–1.044) | 0.273 | ||
LVESD (mm) | 1.004 (0.974–1.035 | 0.788 | ||
sPAP (mmHg) | 1.028 (1.012–1.044) | <0.001 | 0.974 (0.928–1.022) | 0.285 |
AVA (cm2) | 0.231 (0.055–0.967) | 0.045 | 0.268 (0.014–5.192) | 0.384 |
AV max (m/s) | 0.846 (0.605–1.182) | 0.327 | ||
AV dpmax (mmHg) | 0.995 (0.985–1.004) | 0.249 | ||
AV dpmean (mmHg) | 0.992 (0.978–1.006) | 0.267 | ||
Mitral regurgitation ≥ II° | 1.319 (0.841–2.069) | 0.229 | ||
Tricuspid regurgitation ≥ II° | 1.890 (1.166–3.065) | 0.010 | 3.119 (1.217–7.994) | 0.018 |
Paravalvular regurgitation ≥ II° | 1.720 (0.792–3.733) | 0.170 | ||
Measurements of RHC | ||||
sPAP (mmHg) | 1.019 (1.008–1.030) | 0.001 | 1.015 (0.974–1.058) | 0.480 |
mPAP (mmHg) | 1.032 (1.014–1.051) | 0.001 | 1.026 (0.874–1.203) | 0.756 |
dPAP (mmHg) | 1.034 (1.009–1.059) | 0.008 | 0.912 (0.841–0.990) | 0.027 |
mPCWP (mmHg) | 1.024 (1.001–1.047) | 0.041 | 1.043 (0.931–1.170) | 0.467 |
DPG (mmHg) | 1.015 (0.973–1.059) | 0.480 | ||
PVR (WU) | 1.167 (1.077–1.265) | <0.001 | 1.079 (0.867–1.344) | 0.494 |
PVR > 3 (WU) | 2.414 (1.510–3.859) | <0.001 | 0.492 (0.093–2.615) | 0.406 |
CO (L/min) | 0.859 (0.697–1.060) | 0.156 | ||
Procedurale data | ||||
Transfemoral approach | 0.540 (0.338–0.862) | 0.010 | 0.546 (0.230–1.297) | 0.171 |
CoreValve | 0.990 (0.578–1.696) | 0.971 | ||
JenaValve | 1.681 (0.981–2.880) | 0.059 | 0.478 (0.121–1.882) | 0.291 |
Edwards | 0.702 (0.448–1.099) | 0.121 | ||
Major vascular complications | 3.351 (1.953–5.749) | <0.001 | 4.194 (1.272–13.829) | 0.019 |
AUC | p-Value | Cut-Off | Sensitivity | Specificity | Youden Index | |
---|---|---|---|---|---|---|
Measurements of RHC-overall cohort | ||||||
sPAP (mmHg) | 0.620 | 0.002 | 49.50 | 0.69 | 0.53 | 0.22 |
mPAP (mmHg) | 0.623 | 0.001 | 34.50 | 0.62 | 0.60 | 0.22 |
dPAP (mmHg) | 0.599 | 0.010 | 15.50 | 0.79 | 0.60 | 0.19 |
mPCWP (mmHg) | 0.586 | 0.036 | 16.50 | 0.77 | 0.40 | 0.16 |
DPG (mmHg) | 0.511 | 0.772 | 1.50 | 0.36 | 0.73 | 0.09 |
PVR (WU) | 0.631 | 0.001 | 3.15 | 0.59 | 0.67 | 0.26 |
TPG (mmHg) | 0.575 | 0.053 | 12.50 | 0.55 | 0.60 | 0.16 |
CO (L/min) | 0.431 | 0.082 | 2.45 | 0.99 | 0.05 | 0.03 |
Measurements of RHC-prec-PH | ||||||
sPAP (mmHg) | 0.519 | 0.894 | 37.50 | 1.00 | 0.17 | 0.17 |
mPAP (mmHg) | 0.602 | 0.463 | 30.50 | 0.33 | 0.94 | 0.28 |
dPAP (mmHg) | 0.611 | 0.424 | 15.50 | 0.83 | 0.50 | 0.33 |
mPCWP (mmHg) | 0.486 | 0.920 | 14.50 | 0.33 | 0.83 | 0.17 |
DPG (mmHg) | 0.542 | 0.764 | 8.50 | 0.17 | 1.00 | 0.17 |
PVR (WU) | 0.711 | 0.157 | 3.30 | 1.00 | 0.67 | 0.67 |
TPG (mmHg) | 0.551 | 0.714 | 13.50 | 0.83 | 0.33 | 0.17 |
CO (L/min) | 0.267 | 0.118 | 2.95 | 1.00 | 0.06 | 0.06 |
Measurements of RHC-ipc-PH | ||||||
sPAP (mmHg) | 0.562 | 0.366 | 47.50 | 0.87 | 0.32 | 0.19 |
mPAP (mmHg) | 0.551 | 0.457 | 33.50 | 0.74 | 0.48 | 0.22 |
dPAP (mmHg) | 0.553 | 0.440 | 27.50 | 0.30 | 0.84 | 0.14 |
mPCWP (mmHg) | 0.530 | 0.661 | 19.50 | 0.87 | 0.36 | 0.13 |
DPG (mmHg) | 0.523 | 0.739 | -5.50 | 0.87 | 0.32 | 0.19 |
PVR (WU) | 0.449 | 0.475 | 2.08 | 0.48 | 0.56 | 0.03 |
TPG (mmHg) | 0.511 | 0.876 | 7.50 | 0.91 | 0.19 | 0.10 |
CO (L/min) | 0.395 | 0.141 | 7.40 | 0.10 | 1.00 | 0.09 |
Measurements of RHC-borderlinepc-PH | ||||||
sPAP (mmHg) | 0.514 | 0.854 | 81.50 | 0.29 | 0.91 | 0.20 |
mPAP (mmHg) | 0.513 | 0.854 | 50.50 | 0.29 | 0.89 | 0.18 |
dPAP (mmHg) | 0.467 | 0.636 | 12.00 | 1.00 | 0.06 | 0.06 |
mPCWP (mmHg) | 0.490 | 0.889 | 37.50 | 0.14 | 0.96 | 0.10 |
DPG (mmHg) | 0.511 | 0.872 | 1.50 | 0.32 | 0.78 | 0.10 |
PVR (WU) | 0.574 | 0.290 | 4.22 | 0.68 | 0.52 | 0.20 |
TPG (mmHg) | 0.535 | 0.614 | 19.50 | 0.32 | 0.82 | 0.14 |
CO (L/min) | 0.557 | 0.413 | 3.19 | 0.75 | 0.41 | 0.16 |
Measurements of RHC-cpc-PH | ||||||
sPAP (mmHg) | 0.857 | 0.021 | 67.00 | 1.00 | 0.86 | 0.86 |
mPAP (mmHg) | 0.821 | 0.037 | 43.50 | 1.00 | 0.71 | 0.71 |
dPAP (mmHg) | 0.643 | 0.355 | 38.50 | 0.50 | 0.86 | 0.36 |
mPCWP (mmHg) | 0.482 | 0.908 | 16.50 | 1.00 | 0.14 | 0.14 |
DPG (mmHg) | 0.821 | 0.037 | 9.50 | 0.75 | 0.86 | 0.61 |
PVR (WU) | 0.729 | 0.156 | 4.74 | 1.00 | 0.50 | 0.50 |
TPG (mmHg) | 0.898 | 0.013 | 23.50 | 1.00 | 0.86 | 0.86 |
CO (L/min) | 0.429 | 0.643 | 2.92 | 0.88 | 0.29 | 0.16 |
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Boxhammer, E.; Gharibeh, S.X.; Wernly, B.; Kelm, M.; Franz, M.; Kretzschmar, D.; Hoppe, U.C.; Lauten, A.; Lichtenauer, M. Conundrum of Classifying Subtypes of Pulmonary Hypertension—Introducing a Novel Approach to Classify “Borderline” Patients in a Population with Severe Aortic Stenosis Undergoing TAVI. J. Cardiovasc. Dev. Dis. 2022, 9, 294. https://doi.org/10.3390/jcdd9090294
Boxhammer E, Gharibeh SX, Wernly B, Kelm M, Franz M, Kretzschmar D, Hoppe UC, Lauten A, Lichtenauer M. Conundrum of Classifying Subtypes of Pulmonary Hypertension—Introducing a Novel Approach to Classify “Borderline” Patients in a Population with Severe Aortic Stenosis Undergoing TAVI. Journal of Cardiovascular Development and Disease. 2022; 9(9):294. https://doi.org/10.3390/jcdd9090294
Chicago/Turabian StyleBoxhammer, Elke, Sarah X. Gharibeh, Bernhard Wernly, Malte Kelm, Marcus Franz, Daniel Kretzschmar, Uta C. Hoppe, Alexander Lauten, and Michael Lichtenauer. 2022. "Conundrum of Classifying Subtypes of Pulmonary Hypertension—Introducing a Novel Approach to Classify “Borderline” Patients in a Population with Severe Aortic Stenosis Undergoing TAVI" Journal of Cardiovascular Development and Disease 9, no. 9: 294. https://doi.org/10.3390/jcdd9090294