THE RIGHT VENTRICLE IN PULMONARY HYPERTENSION R. DRAGU Cardiology Dept. Rambam Health Care Campus Rappaport Faculty of Medicine Technion, Israel
Why the Right Ventricle? Pulmonary hypertension (PH) Right ventricle (RV) function Outcome
RV dysfunction & outcome PH & RV dysfunction Ghio, et al. JACC 2001;37:138-188
RV dysfunction & outcome I-II III IV <250 m 250-350 m >350 m NYHA class 6MWD Humbert, et al. Circ 2010;122:156-163
RV dysfunction & outcome Galie et al. Eur H J 2009;30:2493-2537.
Variable Depends on: RV response to PH PH type Onset rapidity PH severity Prediction of future dysfunction LIMITED
RV Chamber characteristics Thinner free wall Lower mass Different geometry Greater distensibility Operates at higher volumes Difference from LV
RV response in PH Van Wolferen et al. Eur Heart J 2008; 29:120-7.
RV response to PH Ea Ea Haddad et al. Circulation 2008; 117:1436-48. Naeije et al. Eur Heart J 2007;9,H5 H9.
RV afterload PVR used in clinical practice as equivalent for afterload may not reflect its complex nature Pulmonary arterial system Low impedance / high distensible High compliance Low resistance Low peripheral pulse wave reflection coefficient
Pulmonary circulation Systemic circulation Resistance small arteries arterioles Compliance aorta Pulmonary circulation Resistance small arteries arterioles Compliance entire pulmonary circulation
Windkessel model
RC constant
Capacitance and outcome Mahapatra et al. JACC 2006;47, 799-806 Dragu et al. IHS Congress 2013
Capacitance and outcome (ml/mmhg) Dragu et al. IHS Congress 2013
Assessment of RV function in PH Mechanisms of RV failure in PH Prognostic implications Effect of PH-specific tx on RV
Parameters that reflect RV function Echocardiography RA area 1 RV Area 1 TAPSE 1,2 Tei index 3 RV fractional area change 2 Degree of tricuspid regurgitation 2 Pericardial effusion 4 Inferior vena cava collapsibility 2 Superior vena cava flow velocity pattern 2 LV eccentricity index 2 RV filling pressure 5 MRI RV EF% and SV 6 Mass index 7 and geometry 8 RHC Right atrial pressure 9 Cardiac index 10 Biomarkers NT-proBNP 11 Troponin T 12 1. Grünig, et al. DMW 2010. 2. Ghio S, et al. Int J Cardiol 2010. 3. Tei C, et al. J Am Soc Echocardiogr 1996. 4. Raymond RJ, et al. JACC 2002. 5. Utsunomiya H, et al. J Am Soc Echocardiogr 2009. 6. van de Veerdonk M, et al. JACC 2011. 7. Hagger, et al. Rheumatology 2009. 8. Mauritz, et al. Chest 2012. 9. McLaughlin VV, et al. Circulation 2002. 10. D Alonzo GE, et al. Ann Intern Med 1991. 11. Nagaya N, et al. JACC 1998. 12. Torbicki A, et al. Circulation 2003.
Echo Variables in good correlation with: Hemodynamics Anatomy Limited visualisation of RV: Complex geometry Extensive trabeculations Retrosternal position
Cl (L/min/m 2 ) Six-minute walk (m) Echo - Pericardial effusion 5 r = -0.40 p < 0.001 500 r = -0.50 p < 0.001 4 400 3 300 2 200 1 100 0 None Trace Small Moderate 0 None Trace Small Moderate Effusion size Effusion size Hinderliter, et al. AJC 1999; 84:481-4.
Freedom from composite endpoints (%) Survival (%) Cumulative survival Echo - Pericardial effusion 100 80 60 No effusion Effusion 1.00 Non pericardial effusion 40 20 0 0 1 2 3 4 5 Time (years) 100 80 60 No effusion 40 Effusion 20 0 0 1 2 3 4 5 Time (years) 0.75 0.50 0.25 0.0 Pericardial effusion Logrank p-value 0.028 12 24 36 Time (months) Raymond RJ, et al. JACC 2002; 39:1214-9. Zhang, et al. Chest 2011; 140:301-9.
Echo - TAPSE Normal TAPSE Longitudinal movement of lateral tricuspid annulus towards apex at peak systole Abundant longitudinal fibres Low TAPSE Correlates with RV systolic function Rudski LG, et al. J Am Soc Echocardiogr 2010; 23:685-713.
RA area index (cm 2 /m) RV area index (cm 2 /m) Diastolic eccentricity index Systolic eccentricity index Cardiac index (l/min/m 2 ) Mixed venous O 2 (%) Echo - TAPSE 4 3 2 1 p< 0.0001 * 80 70 60 p< 0.0001 * 50 40 1.8 < 1.8 1.8 < 1.8 Systolic function Remodelling RV / LV 24 20 16 12 8 p< 0.0001 24 p= 0.01 * * 20 16 12 8 1.8 < 1.8 1.8 < 1.8 2.0 1.6 1.2 p= 0.002 * 2.8 2.4 2.0 1.6 1.2 p= 0.009 * 0.8 0.8 1.8 < 1.8 1.8 < 1.8 Forfia, et al. Am J Respir Crit Care Med 2006; 174:1034-41.
0.2 RV diameter < 36.5 mm RV diameter 36.5 RV diameter > 36.5 6.6 (95%CI 3.3-13.2) 0.0 0 12 24 36 48 Months RV diameter > 36.5 mm Survival curves in patients with RV wall thickness > 6.6 mm 15.9 (95%CI 9.4-26.8) 1.00 0.7 0.5 Echo - RV morphology Survival curves in patients with RV wall thickness 6.6 mm 1.00 0.7 0.5 Death rate per 100 patient-year: 0.2 0.0 RV diameter 36.5 RV diameter > 36.5 0 12 24 36 48 Months Ghio, et al. AJC 2011; 107:628-32.
Echo - 2D longitudinal strain Percentage change in myocardial deformation Doppler or speckles More negative = better contractility Unlike TAPSE it takes whole RV into account Load dependent Freed, et al. Cur Cardiol Rep 2012; online early pub.
Proportion with symptom progression, % Survival, % Echo - 2D longitudinal strain 25 20 * 100% 80% Loop diuretics * Oedema despite loop diuretics 100 p < 0.005 15 60% * 80 10 40% 60 5 0 20% 0% 40 0 2 4 Follow-up, years Mild (>-20%) Moderate (-20 to -12.5%) Severe (<-12.5%) Sachdev, et al. Chest 2011; 139:1299-1309.
Echo - 3D Rapid acquisition of full volume 3D data Accurate & reproducible measures of RV ESV (ml) EDV (ml) EF (%) Correlation 0.89 (-9ml) 0.87 (-14ml) 0.87 (-2%) Sugeng, et al. JACC Imag 2010; 3:10-8.
Survival (%) CMRI - Stroke volume 64 IPAH prevalent patients Measured at baseline by MRI Mean follow-up: 32 months 100 80 60 40 20 0 SVI > 25 ml/m 2 SVI 25 ml/m 2 0 10 20 30 40 50 60 70 80 Time (months) p = 0.009 Van Wolferen SA, et al. Eur Heart J 2007; 28:1250-7.
1-Clinical worsening (%) CMRI - RV ejection fraction 100 75 50 25 0 Log-rank p = 0.0063 0 200 400 600 Days to event RVEF < 39% RVEF 39% p < 0.001 0 25 50 75 100 125 Time (months) RVEF > 35% RVEF < 35% Freed et al. JCMR 2012; 14:11. van de Veerdonk et al. JACC 2011; 58:2511-9.
CMRI - Myocardial delayed enhancement
1-Clinical worsening (%) Total delayed enhancement mass (g) CMRI - Myocardial delayed enhancement Right ventricular insertion point-late gadolinium enhancement (RVIP-LGE) 100 75 Log-rank p = 0.0065 12.00 10.00 8.00 50 6.00 25 0 0 200 400 600 Days to event 4.00 2.00 0.00 0.25 0.50 0.75 1.00 1.25 Ventricular mass index RVIP-LGE No RVIP-LGE Freed, et al. JCMR 2012; 14:11. Shehata, et al. AJR 2011; 196:87-94.
Plasma BNP levels (pg/ml) Plasma BNP levels (pg/ml) Plasma BNP levels (pg/ml) BNP as surrogate of RV function 300 * 10 3 r = -0.73. p < 0.001 10 3 r = 0.11. p = NS 200 10 2 10 2 100 * 10 1 10 1 0 Cont. RVVO RVPO 1 0 20 30 40 50 60 70 RVEF (%) 1 0 100 200 300 400 RVEDVI (ml/m 2 ) *p < 0.05 vs control p < 0.05 vs RVVO 44 patients 18 - ASD (RVVO) 16 - CTEPH (RVPO) Nagaya N, et al. J Am Coll Cardiol 1998; 31:202-8.
Cumulative survival Prognostic value of cardiac troponin T in PAH and CTEPH patients 1.0 0.8 0.6 p= 0.0003 p= 0.005 Cardiac troponin T (-) 0.4 p= 0.001 0.2 Cardiac troponin T (+) 0.0 Numbers at risk, n 0 6 12 18 24 Time (months) 48 43 33 30 25 8 4 4 2 2 Torbicki A, et al. Circulation 2003; 108:844-8.
Conclusion Sir William Harvey 1616 De Motu Cardis Thus the right ventricle may be said to be made for the sake of transmitting blood through the lungs, not for nourishing them. Paucity of knowledge regarding RV Understanding of RV adaptation to PH crucial for Tx.