Prognostic value of echocardiographic parameters in patients with pulmonary arterial hypertension (PAH) treated with targeted therapies E. Beciani, M. Palazzini, C. Bachetti, F. Sgro, E. Conficoni, E. Gotti, G. Mazzanti, A. Manes, A. Branzi, N. Galie Institute of Cardiology, University of Bologna, Italy
Echocardiographic parameters correlated with prognosis in PAH patients Study Year n Diagnosis Therapy Multivariated analyses Eysmann et al 1986-1988 26 IPAH Conventional Peric. effusion Yeo et al 1987-1994 53 IPAH Conventional Tei index Tei et al 1987-1994 26 IPAH Conventional Tei index Raymond et al Mahapatra et al Mustabante et al 1994-1995 79 IPAH Epoprostenol Peric. effusion RA Area index 1999 54 IPAH Conventional PAVC 1993-2000 25 IPAH Non specific RA Area TR Area Forfia et al 2004 63 IPAH (47) + PI Prostanoids, ERA, PDE5I Ghio et al. 1996-2004 59 IPAH Prostanoids, ERA, PDE5I Peric. effusion TAPSE TAPSE
Purpose To prospectively assess the prognostic value of echocardiographic parameters in a large cohort of PAH patients treated according to current guidelines including combination therapy
Methods Between 1 st September 2000 and 31 st December 2009 we enrolled 338 patients (mean age 52±17; females 62%) with PAH of different etiologies At baseline, patients underwent clinical evaluation, WHO functional class assessment, six minute walk distance (6MWD), right heart catheterization and echocardiography
Galiè. N et al Eur Heart J and Eur Respir J, 2009
PH echocardiographic protocol 6 65 parameters
Parameters included in the analysis (11) RVTD Area index (cm 2 /m 2 ) LVTD Area index (cm2/m2) RA Area index (cm2/m2) TR V max (m/sec) RV Tei index TAPSE (cm) Pericardial effusion(y/n) PFO (Y/N) TR Area (cm2) LV TD EI LV TS EI
Results
Demographic and baseline functional and exercise capacity characteristics 338 patients Age (years) 52 ± 17 (12-81) Female/Male 209/129 (61.8% F) I-II 100 (30%) WHO FC (335 pts) III 216 (64.5%) IV 18 (5.5%) 6MWD (m, 316 pts) 358 ± 129 (50-650)
Etiology HIV-PAH (n 31) 9% OTHER (n 3) 1% CTD-PAH (n 91) 27% IPAH-HPAH-DRUGS (n 213) 63%
Baseline Haemodynamic Characteristics Haemodynamic parameters Mean ± SD RAP (mmhg) 8 ± 5 PAPm (mmhg) 53 ± 14 CI (l/min/m 2 ) 2.4 ± 0.7 PVR (Wood Unit) 12.4 ± 7.0 PA SatO 2 (%) 60 ± 9
Echocardiographic parameters - 1 PARAMETER n Mean ± SD Normal RVTD Area index (cm 2 /m 2 ) 329 17.0 ± 4.9 7.1 ± 1.4 LVTD Area index (cm 2 /m 2 ) 328 11.5 ± 3.3 16.1 ± 2.4 RA Area index (cm 2 /m 2 ) 329 14.3 ± 4.8 9.1 ± 1.7
Echocardiographic parameters - 2 D2 D1 PARAMETER n Average ± SD Normal TR V max (m/sec) 310 4.3 ± 0.6 2.6 ± 0.5 TR Area (cm 2 ) 322 6.7 ± 5.6 0.7 ± 0.8 LV TD EI 334 1.41 ± 0.42 1.01 ± 0.07 LV TS EI 334 1.57 ± 0.54 1.00 ± 0.01
Echocardiographic parameters - 3 T R PARAMETER n Average ± SD Normal RV Tei index 295 0.73 ± 0.35 0.28 ± 0.04 TAPSE (cm) 89 1.67 ± 0.50 >2 Pericardial effusion(y/n) 333 143/190 (42.9%) / PFO (Y/N) 324 81/243 (25%) 24.3%
PAH specific therapy-1 No specific therapy (n 13) 4% Monotherapy (n 138) 50% 15% CCB (n 50) 81% Specific therapy (n 275) 50% Combination therapy (n 137)
PAH specific therapy-2 Monotherapy (n 138) Combination therapy (n 137) Prostanoids (n 11) Triple tp (n 48) 15% PDE 5 (n 56) 41% 35% 51% ERA (n 71) 65% Double tp (n 89)
Survival Kaplan-Meier survival curve 83.9% 67.3% 57.5% Follow-up 36.7 ± 30.6 months 125 Deceased 21 Lost follow-up 4 Lung Transplant Months N % 338 246 185 143 108 79 51 31 20 100 84 74 67 61 56 51 45 43
Univariate analysis Demographic, functional and exercise capacity variables Variable n Univariate HR (95% CI) p Gender (M) 338 1.626 (1.141; 2.316) 0.007 Age (years) 338 1.036 (1.024; 1.049) <0.0001 WHO FC (III-IV) 335 6.218 (3.343; 11.564) <0.0001 6MWD (mts) 316 0.994 (0.992; 0.996) <0.0001
Univariate analysis Demographic, functional and exercise capacity variables Variable n Univariate HR (95% CI) p Gender (M) 338 1.626 (1.141; 2.316) 0.007 Age (years) 338 1.036 (1.024; 1.049) <0.0001 WHO FC (III-IV) 335 6.218 (3.343; 11.564) <0.0001 6MWD (mts) 316 0.994 (0.992; 0.996) <0.0001
Univariate analysis Haemodynamic variables Variable n Univariate HR (95% CI) p RAP (mmhg) 333 1.052 (1.018; 1.087) 0.002 PAPm (mmhg) 333 0.999 (0.986; 1.011) 0.856 CI (L/min/m 2 ) 333 0.743 (0.562; 0.984) 0.038 PVR (mmhg) 333 1.007 (0.984; 1.030) 0.554 PA SatO 2 (%) 333 0.960 (0.942; 0.978) < 0.0001
Univariate analysis Haemodynamic variables Variable n Univariate HR (95% CI) p RAP (mmhg) 333 1.052 (1.018; 1.087) 0.002 PAPm (mmhg) 333 0.999 (0.986; 1.011) 0.856 CI (L/min/m 2 ) 333 0.743 (0.562; 0.984) 0.038 PVR (mmhg) 333 1.007 (0.984; 1.030) 0.554 PA SatO 2 (%) 333 0.960 (0.942; 0.978) < 0.0001
Univariate analysis Echocardiographic variables Variables n Univariate HR (95% CI) p RV TD Area index (cm 2 /m 2 ) 329 1.036 (1.002; 1.071) 0.039 LV TD Area index (cm 2 /m 2 ) 328 0.920 (0.870; 0.973) 0.003 RA Area index (cm 2 /m 2 ) 329 1.065 (1.032-1.099) < 0.0001 TR Vmax (m/sec) 310 1.004 (1.001; 1.007) 0.009 TR Area (cm 2 ) 322 1.047 (1.022; 1.072) < 0.0001
Univariate analysis Echocardiographic variables Variables n Univariate HR (95% CI) p RV TD Area index (cm 2 /m 2 ) 329 1.036 (1.002; 1.071) 0.039 LV TD Area index (cm 2 /m 2 ) 328 0.920 (0.870; 0.973) 0.003 RA Area index (cm 2 /m 2 ) 329 1.065 (1.032-1.099) < 0.0001 TR Vmax (m/sec) 310 1.004 (1.001; 1.007) 0.009 TR Area (cm 2 ) 322 1.047 (1.022; 1.072) < 0.0001
Univariate analysis Echocardiographic variables Variables n Univariate HR (95% CI) p LV TD EI 334 1.140 (0.764; 1.701) 0.522 LV TS EI 334 1.194 (0.883; 1.616) 0.250 RV Tei index 295 1.159 (0.701-1.917) 0.566 Pericardial effusion (YES) 333 1.742 (1.225; 2.478) 0.002 TAPSE (cm) 89 1.337 (0.352; 5.083) 0.670 PFO (YES) 324 1.055 (0.701; 1.588) 0.797
Univariate analysis Echocardiographic variables Variables n Univariate HR (95% CI) p LV TD EI 334 1.140 (0.764; 1.701) 0.522 LV TS EI 334 1.194 (0.883; 1.616) 0.250 RV Tei index 295 1.159 (0.701-1.917) 0.566 Pericardial effusion (YES) 333 1.742 (1.225; 2.478) 0.002 TAPSE (cm) 89 1.337 (0.352; 5.083) 0.670 PFO (YES) 324 1.055 (0.701; 1.588) 0.797
Multivariate analysis (Including all parameters with p<0.05 at UA) PAH (n= 309) Variabile Univariate HR (95% CI) p Age (years) 1.021 (1.007-1.036) 0.003 Male 1.748 (1.179-2.592) 0.005 6MWD (mts) 0.995 (0.993-0.997) <0.0001 RA Area index (cm 2 /m 2 ) 1.042 (1.002-1.084) 0.040
RA Area Index (cm 2 /m 2 ) Pearson correlation r = 0.564 p = 0.0001 TR Area (cm 2 )
Survival Survival based on the median RA area index 74.9% < 13.5cm 2 /m 2 43% 13.5cm 2 /m 2 Log rank Test p<0.001 N N Months 165 131 92 72 56 40 22 11 7 < 13.5 164 109 87 66 47 36 26 18 11 13.5
Survival Survival based on the median 6MWD 72.6% 360 mt 47.2% < 360 mt Log rank Test p<0.001 N N Months 154 108 76 56 39 30 17 11 7 360 162 133 105 84 66 47 32 19 12 < 360
Survival Survival stratification based on the median age 70.8% < 54 year 44.5% 54 year Log rank Test p<0.001 N N Months 166 129 107 84 67 51 33 21 14 < 54 172 117 78 59 41 28 18 10 6 54
Survival Survival stratification based on gender 70.8?% 63.8% F 47.5% 44.5?% M Log rank Test p=0.007 N Months 209 154 118 96 76 58 38 24 16 F N 129 92 67 47 32 21 13 7 4 M
Conclusions (1) This study is currently the largest available on the prognostic value of echocardiographic parameters in patients with PAH treated according to current guidelines Different clinical, exercise capacity, haemodynamic and echocardiographic parameters appear to be correlated to survival in univariate analyses. These results are in keeping with studies available in the literature The multivariate analysis identify four independent prognostic factors in patients with PAH: age, gender, functional capacity and right atrium area index
Conclusions (2) The right atrium area index is correlated with the tricuspid regurgitation area and represents an indicator of the pathological remodeling of the heart It is not clear if the right atrium enlargement (and the tricuspid regurgitation area) can regress after the use of the drugs approved for PAH (1,2) 1. Hinderliter AL, et al: Effects of long-term infusion of prostacyclin (epoprostenol) on echocardiographic measures of right ventricular structure and function in primary pulmonary hypertension. Primary Pulmonary Hypertension Study Group. Circulation 1997;95(6):1479-1486. 2. Galie N, et al.: Effects of the oral endothelin-receptor antagonist bosentan on echocardiographic and doppler measures in patients with pulmonary arterial hypertension. J Am Coll Cardiol 2003;41(8):1380-1386.