Prognostic value of echocardiographic parameters in patients with pulmonary arterial hypertension (PAH) treated with targeted therapies
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1 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
2 Echocardiographic parameters correlated with prognosis in PAH patients Study Year n Diagnosis Therapy Multivariated analyses Eysmann et al IPAH Conventional Peric. effusion Yeo et al IPAH Conventional Tei index Tei et al IPAH Conventional Tei index Raymond et al Mahapatra et al Mustabante et al IPAH Epoprostenol Peric. effusion RA Area index IPAH Conventional PAVC IPAH Non specific RA Area TR Area Forfia et al IPAH (47) + PI Prostanoids, ERA, PDE5I Ghio et al IPAH Prostanoids, ERA, PDE5I Peric. effusion TAPSE TAPSE
3 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
4 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
5 Galiè. N et al Eur Heart J and Eur Respir J, 2009
6 PH echocardiographic protocol 6 65 parameters
7 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
8 Results
9 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)
10 Etiology HIV-PAH (n 31) 9% OTHER (n 3) 1% CTD-PAH (n 91) 27% IPAH-HPAH-DRUGS (n 213) 63%
11 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
12 Echocardiographic parameters - 1 PARAMETER n Mean ± SD Normal RVTD Area index (cm 2 /m 2 ) ± ± 1.4 LVTD Area index (cm 2 /m 2 ) ± ± 2.4 RA Area index (cm 2 /m 2 ) ± ± 1.7
13 Echocardiographic parameters - 2 D2 D1 PARAMETER n Average ± SD Normal TR V max (m/sec) ± ± 0.5 TR Area (cm 2 ) ± ± 0.8 LV TD EI ± ± 0.07 LV TS EI ± ± 0.01
14 Echocardiographic parameters - 3 T R PARAMETER n Average ± SD Normal RV Tei index ± ± 0.04 TAPSE (cm) ± 0.50 >2 Pericardial effusion(y/n) /190 (42.9%) / PFO (Y/N) /243 (25%) 24.3%
15 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)
16 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)
17 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 %
18 Univariate analysis Demographic, functional and exercise capacity variables Variable n Univariate HR (95% CI) p Gender (M) (1.141; 2.316) Age (years) (1.024; 1.049) < WHO FC (III-IV) (3.343; ) < MWD (mts) (0.992; 0.996) <0.0001
19 Univariate analysis Demographic, functional and exercise capacity variables Variable n Univariate HR (95% CI) p Gender (M) (1.141; 2.316) Age (years) (1.024; 1.049) < WHO FC (III-IV) (3.343; ) < MWD (mts) (0.992; 0.996) <0.0001
20 Univariate analysis Haemodynamic variables Variable n Univariate HR (95% CI) p RAP (mmhg) (1.018; 1.087) PAPm (mmhg) (0.986; 1.011) CI (L/min/m 2 ) (0.562; 0.984) PVR (mmhg) (0.984; 1.030) PA SatO 2 (%) (0.942; 0.978) <
21 Univariate analysis Haemodynamic variables Variable n Univariate HR (95% CI) p RAP (mmhg) (1.018; 1.087) PAPm (mmhg) (0.986; 1.011) CI (L/min/m 2 ) (0.562; 0.984) PVR (mmhg) (0.984; 1.030) PA SatO 2 (%) (0.942; 0.978) <
22 Univariate analysis Echocardiographic variables Variables n Univariate HR (95% CI) p RV TD Area index (cm 2 /m 2 ) (1.002; 1.071) LV TD Area index (cm 2 /m 2 ) (0.870; 0.973) RA Area index (cm 2 /m 2 ) ( ) < TR Vmax (m/sec) (1.001; 1.007) TR Area (cm 2 ) (1.022; 1.072) <
23 Univariate analysis Echocardiographic variables Variables n Univariate HR (95% CI) p RV TD Area index (cm 2 /m 2 ) (1.002; 1.071) LV TD Area index (cm 2 /m 2 ) (0.870; 0.973) RA Area index (cm 2 /m 2 ) ( ) < TR Vmax (m/sec) (1.001; 1.007) TR Area (cm 2 ) (1.022; 1.072) <
24 Univariate analysis Echocardiographic variables Variables n Univariate HR (95% CI) p LV TD EI (0.764; 1.701) LV TS EI (0.883; 1.616) RV Tei index ( ) Pericardial effusion (YES) (1.225; 2.478) TAPSE (cm) (0.352; 5.083) PFO (YES) (0.701; 1.588) 0.797
25 Univariate analysis Echocardiographic variables Variables n Univariate HR (95% CI) p LV TD EI (0.764; 1.701) LV TS EI (0.883; 1.616) RV Tei index ( ) Pericardial effusion (YES) (1.225; 2.478) TAPSE (cm) (0.352; 5.083) PFO (YES) (0.701; 1.588) 0.797
26 Multivariate analysis (Including all parameters with p<0.05 at UA) PAH (n= 309) Variabile Univariate HR (95% CI) p Age (years) ( ) Male ( ) MWD (mts) ( ) < RA Area index (cm 2 /m 2 ) ( ) 0.040
27 RA Area Index (cm 2 /m 2 ) Pearson correlation r = p = TR Area (cm 2 )
28 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 <
29 Survival Survival based on the median 6MWD 72.6% 360 mt 47.2% < 360 mt Log rank Test p<0.001 N N Months < 360
30 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 <
31 Survival Survival stratification based on gender 70.8?% 63.8% F 47.5% 44.5?% M Log rank Test p=0.007 N Months F N M
32 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
33 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): 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):
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