STUDY POPULATION. Of 480 subjects enrolled across the two sites, 47 (10%) patients with no TR and 14 (3%) with a coaptation defect resulting in severe, free-flowing TR were excluded, yielding 419 patients (Karolinska: n = 296 (70%); Umeå: n = 123 (30%)) for analysis. Clinical characteristics, invasive and echocardiographic data are provided in Table 1. Fifty-two percent of the subjects were female. Twenty percent (n = 86) presented with AF and 7% (n = 31) were on pacemaker therapy. A wide range of invasive pressures were observed for RAPmean (1 to 29mmHg), PAPmean (7 to 99mmHg) and PAPsystolic (12 to 136mmHg). One hundred and seventy-nine patients (44%) presented with reduced RV systolic function as suggested by TAPSE < 16mm[10]. Echocardiographic images of the IVC were either not available or did not permit optimal evaluation in a small fraction (n = 32; 7.6%). Two hundred and forty patients (57%) presented with mild TR, 122 (29%) with moderate TR, and 57 (14%) with severe TR. An illustration of echocardiographic evaluation of PA pressures is provided in Fig. 1.
Table 1
Clinical Characteristics, invasive and echocardiographic data of patient population. Data presented as mean ± SD/ median (Q1; Q3) or number (%)
| Patient population (n = 419) |
Demographics | |
Age (years) | 62 ± 15 |
Female | 218 (52) |
Medical history | |
Diabetes | 59 (14) |
Hypertension | 188 (44) |
Atrial Fibrillation | 86 (20) |
Clinical assessment | |
Heart rate (bpm) | 72 ± 14 |
Body surface area (m2) | 1.9 ± 0.9 |
Systolic blood pressure (mmHg) | 123 ± 23 |
Diastolic blood pressure (mmHg) | 70 ± 13 |
Indication for RHC | |
PAH or CTEPH | 169 (40) |
Heart Failure | 176 (42) |
Post-cardiac transplantation | 8 (2) |
Constriction | 26 (6) |
Arrhythmogenic right ventricular dysplasia | 25 (6) |
Others | 15 (4) |
RHC | |
PAPsystolic (mmHg) | 49 (37;66) |
PAPdiastolic (mmHg) | 20 (14;25) |
PAPmean (mmHg) | 32 (23;41) |
RAPmean (mmHg) | 7 (4;11) |
Echocardiography | |
RVIDbasal (mm) | 42 ± 8 |
TAPSE (mm) | 17 ± 5 |
RA area (cm2) | 22 ± 7 |
Doppler | |
TRVmax (m/s) | 3.2 (2.7;3.8) |
RHC right heart catheterization, PAH pulmonary arterial hypertension, CTEPH chronic thromboembolic pulmonary hypertension, PAP pulmonary artery pressure, RAP right atrial pressure, RVID right ventricular internal diameter end-diastole, TAPSE tricuspid annular plane systolic excursion, TRVmax tricuspid regurgitation max velocity, RA right area. |
ACCURACY OF TRV max TO IDENTIFY PRESENCE OF PH. TRVmax demonstrated strong association with invasive PAPmean (r = 0.75, p < 0.001) and a cut-off of 2.8m/sec demonstrated good ability to identify PH, defined as invasive PAPmean ≥ 25mmHg (AUC = 0.87, CI 0.84 to 0.91, p < 0.001). Sensitivity analysis for different echocardiographic cut-offs to is presented in Table 2. At 2.8m/sec, TRVmax demonstrated 89% sensitivity and 62% specificity to identify PH, with a 38% false positive rate. Forty-five patients (15%) with a TRVmax >2.8m/sec demonstrated normal PA pressures on RHC. At 3.4m/sec, TRVmax demonstrated 94% specificity and 62% sensitivity, and false positive rate fell to 5.9%. Even when balanced sensitivity and specificity was identified at a 3.0m/sec cut-off (80% sensitivity, 80% specificity), a 20% false positive rate was observed. Supplementary sensitivity analysis was also performed considering PAPmean ≥ 20mmHg which revealed similar results (Supplementary Table 1). On Bland-Altman analysis, echocardiographic TR gradient demonstrated a mean bias of + 2.5mmHg with invasive RV-RA gradient (95% limits of agreement + 23 to -18mmHg).
Table 2
Sensitivity, specificity, positive predictive value, negative predictive value for echocardiographic cut-offs to identify corresponding RHC values
| Cut off | RHC value | Sensitivity (%) | Specificity (%) | Positive predictive value (%) | Negative predictive value (%) |
TRVmax | 2.8m/sec | PAPmean≥25mmHg | 89 | 62 | 85 | 68 |
TRVmax | 3.0m/sec | PAPmean≥25mmHg | 80 | 80 | 90 | 62 |
TRVmax | 3.4m/sec | PAPmean≥25mmHg | 62 | 94 | 96 | 50 |
Estimated RAP | 7mmHg | RAPmean>7mmHg | 84 | 68 | 69 | 85 |
ACCURACY OF IVC TO ESTIMATE RAP mean CATEGORIES. RAPmean estimated as per ASE/EACVI recommendations[10] demonstrated a good ability to identify invasive RAPmean >7mmHg (AUC: 0.80; CI 0.76 to 0.85, p < 0.001). However, Sensitivity analysis demonstrated a modest 68% specificity and 69% PPV (Table 2). Further, 67 subjects (32%) that demonstrated elevated RAPmean estimated by echocardiography demonstrated normal invasive RAPmean. When invasive RAPmean was plotted against echocardiographic estimates, median (IQR) for the 3,8 and 15mmHg IVC-estimated subgroups were 5 (3 to 7mmHg), 8 (5 to 10mmHg) and 13 (8 to 16mmHg) (p < 0.001 for comparison between groups). A total of 122 patients displayed an IVC-estimated RAPmean of 15mmHg. In this subgroup, 15 (12%) demonstrated an invasive RAPmean < 5mmHg, and 45 (37%), an RAPmean ≤ 10mmHg. On Bland-Altman analysis, minimal bias but poor precision was observed between modalities (mean bias: -0.1mmHg; 95% limits of agreement + 9.1 to -9.5mmHg).
ACCURACY OF ECHOCARDIOGRAPHY TO EVALUATE INVASIVE PAP systolic . Echocardiographic PAPsystolic as per the ASE/EACVI approach demonstrated strong association with invasive PAPsystolic (r = 0.86, p < 0.001) (Fig. 2a). Bias and limits of agreement between echocardiographic estimates of PAPsystolic and RHC are presented in Table 3 and Fig. 2b. Bland-Altman analysis revealed low bias between echocardiography and RHC (mean bias = + 2.4mmHg; CI 1.2-3.5mmHg) with wide limits of agreement (-20 to + 25mmHg) (Fig. 2b). Only 62% of individual echocardiographic estimates were accurate. Echocardiography overestimated RHC by > 10mmHg in 92 of 387 estimates (24%) and underestimated RHC by > 10mmHg in 36 of 387 estimates (10%). Absolute values for magnitude of overestimation were comparable with underestimation (18 ± 5 vs. 18 ± 6mm). When median RAPmean (7mmHg) was incorporated instead of IVC-based estimates [10], association between echocardiographic and invasive PAPsystolic remained strong (r = 0.83, p < 0.001) (Fig. 3a). Bland-Altman analysis displayed relatively lower mean bias between methods (Bias: +1.4mmHg, 95% CI 0.2-2.5mmHg) and comparable limits of agreement (– 22 to + 25mmHg) when compared with the ASE/EACVI approach (Fig. 3b).
Table 3
Bias and limits of agreement between echocardiographic estimates of systolic and mean pulmonary artery pressures and right heart catheterization
Echo Estimate | Bias ± SD | 95% CI | Lower limit (Mean-2SD) | Upper limit (Mean + 2SD) |
PAPsystolic (ASE/EACVI) (mmHg) | + 2.4 ± 11 | 1.2–3.5 | -20 | + 25 |
PAPsystolic (RAP = 7mmHg) (mmHg) | + 1.4 ± 12 | 0.2–2.5 | -22 | + 25 |
PAPmean (ASE/EACVI) (mmHg) | + 1.9 ± 8 | 1.0–2.6 | -14 | + 18 |
PAPmean (RAP = 7mmHg) (mmHg) | + 1.4 ± 9 | 0.5–2.2 | -16 | + 19 |
ACCURACY OF ECHOCARDIOGRAPHY TO EVALUATE INVASIVE PAP mean .
Echocardiographic PAPmean incorporating recommendation-based RAP estimates[10] demonstrated strong association with invasive PAPmean (r = 0.81, p < 0.001) (Fig. 4a). Bias and limits of agreement between echocardiographic estimates of PAPmean and RHC are presented in Table 3. Bland-Altman analysis revealed low bias between methods (mean bias = + 1.9mmHg; 95% CI 1.0-2.6mmHg) with modest precision (limits of agreement = -14 to + 18mmHg) (Fig. 4b). Applying an RAPmean = 7mmHg to echocardiographic PAPmean lowered bias between methods (mean bias = + 1.3mmHg; 95% CI 0.5-2.2mmHg) and showcased comparable limits of agreement (-16 to + 19mmHg) (Fig. 5b).