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Role of the Echocardiogram in the Assessment of Pulmonary Hypertension and the Right Ventricle. Antoine Hage , M.D Director, Solid Organ Transplant Cardiology Co-Director , Pulmonary Hypertension Program Cedars Sinai Heart Institute Clinical Professor of Medicine/ Cardiology
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Role of the Echocardiogram in the Assessment of Pulmonary Hypertension and the Right Ventricle Antoine Hage, M.D Director, Solid Organ Transplant Cardiology Co-Director, Pulmonary Hypertension Program Cedars Sinai Heart Institute Clinical Professor of Medicine/ Cardiology David Geffen School of Medicine at UCLA
Role of Echocardiography in Pulmonary Hypertension: Overview • Definition and classification • Role of ECHO in • Diagnosis (allows identification of patients for whom RHC is required) • Screening high risk patient populations • Evaluation of Structure/ Morphology/ Function/ Hemodynamics of RV and PA (CHD) • Determining etiology / PH group (PAH vs PVH) and secondary causes • Risk stratification (Evaluation of functional and hemodynamic impairment) • Formulating therapeutic options, monitoring disease stability and response to therapy (longitutudinal F/U) • Prognostic evaluation
Hemodynamic Definition of PH/PAH PH Mean PAP ≥25 mm Hg Mean PAP ≥25 mm Hg plusPCWP/LVEDP ≤15 mm Hg PAH ACCF/AHA CECD includes PVR >3 Wood Units Badesch D et al. J Am Coll Cardiol. 2009;54:S55-S66. McLaughlin VV et al. J Am Coll Cardiol. 2009;53:1573-1619.
Clinical Classification of Pulmonary Hypertension (Dana Point 2008) • 3. PH Owing to Lung Diseases and/or Hypoxia • COPD • ILD • Other pulmonary diseases with mixedrestrictive and obstructive pattern • Sleep-disordered breathing • Alveolar hypoventilation disorders • Chronic exposure to high altitude • Developmental abnormalities • 4. CTEPH • 5. PH With Unclear Multifactorial Mechanisms • Hematologic disorders (MPD, splenectomy,..) • Systemic disorders (sarcoidosis, LAM,..) • Metabolic disorders (e.g Thyroid disorders,.. ) • Others (e.g Renal failure/ dialysis, fibrosingmediastinitis,..) • PAH • Idiopathic PAH • Heritable (BMPR2, ALK1, Endoglin) • Drug- and toxin-induced • Persistent PH of newborn • Associated with: • CTD • HIV infection • portal hypertension • CHD • schistosomiasis • chronic hemolytic anemia 1’. PVOD and/or PCH • PH Owing to Left Heart Diseases • Systolic dysfunction • Diastolic dysfunction • Valvular disease Simonneau G et al. J Am Coll Cardiol. 2009;54;S43-S54.
When to Suspect and Screen for PAH • Family history • 6% - 12% prevalence of positive family history. If BMPR2 present, 20% chance of developing PAH. • Autosomal dominant, incomplete penetrance, genetic anticipation • Connective tissue disease • Limited and diffuse scleroderma: 8%- 30% • CREST: up to 20% - 25% • Systemic lupus erythematosus: 4% - 14% • Rheumatoid arthritis up to 21% • Congenital Heart Disease • Reversal of left-to-right shunt • Ventricular septal defect, patent ductusarteriosus, atrialseptal defect • Portal hypertension • Nearly 10% have elevated right ventricular systolic pressure by echo and RHC. • 4% have severe PAH to contraindicate liver transplantation • Deep venous thrombosis/history of pulmonary embolism • Up to 3-4% of survivors • Appetite suppressant or stimulant use • 1/20000 of Fen Phen users more than 3 months • Methamphetamine use • HIV • 0.5% (1/200) patients. • Sickle cell disease, hemodialysis patients, etc
Echocardiography in Pulmonary HTN • Echocardiography is an integral part of the assessment of a patient with PH, Often the first test to detect PH • Evaluates cardiac structure, function and hemodynamics • Rules out congenital heart diseases and shunts* • Provides a reasonably accurate estimate of pulmonary artery pressures • Guides diagnosis and therapy • Helps determine prognosis: Many Echo parameters are prognostic indicators: • RV size and function (eg,TAPSE, S’, FAC, MPI/TEI index) • Pericardial effusion • Estimate of CO/CI and RA pressure (hemodynamics) * May need TEE
Role of Echocardiography in the Screening of Patients at Risk of Developing PH/ PAH
When to Suspect and Screen for PAH • Family history/ Heritable PAH • Connective tissue disease • Congenital Heart Disease • Portal hypertension • Deep venous thrombosis/ history of pulmonary embolism • HIV patients • Appetite suppressant or stimulant use (Methamphetamine) • Sickle cell disease, hemodialysis patients/fistula, sarcoidosis, post-splenectomy etc.
Echocardiographic Criteria Corresponding to Various Levels of Likelihood of Presence of Pulmonary Hypertension * Eg, if RV morphology and function and/or systolic time intervals such as PAAT, or mid systolic deceleration of right ventricular ejection (notching) are suggestive of PH, such diagnosis should be considered “possible” even if Doppler estimate of sPAP is within normal range . # TRV > 2.8 m/Sec corresponds to TIPG > 31 mm Hg, suggest PH except in elderly or very obese patients Galie N, et al: EurRespir J. 2009; 34; 1219-1263
Screening Patient Groups at Risk of Developing PAH • Yearly echocardiography is recommended in patients • At risk for heritable PAH • With CTD, especially patients with scleroderma • Some recommend echo Q 2 years if normal BNP and : • DLCO > 70% and • FVC% /DLCO% < 1.6 • With sickle cell disease • Echocardiography should be considered, in patients with PH-suggestive symptoms • After pulmonary embolism • With HIV infection • With portal hypertension • With prior appetite suppressant use • With sarcoidosis • After splenectomy
Limitations of Echocardiography in PAH1,2 • Experienced technicians and interpreting physicians are essential • Consistency of skilled technicians/readers • Applies to all imaging modalities • Images can be limited in some patient populations • The RV, the chamber of highest concern in PAH, is the least emphasized on the “standard” echocardiography exam • TR jet may be absent in some patients, thus precluding PASP assessment • May overestimate or underestimate actual pulmonary arterial pressure • Can estimate LVEDP (PCWP) or CO/CI, but may prove impractical CI, cardiac index; CO, cardiac output; LVEDP, left ventricular end diastolic pressure; PASP, pulmonary arterial systolic pressure; PCWP, pulmonary capillary wedge pressure; RV, right ventricle; TR, tricuspid regurgitation. 1. Cheitlin et al. Circulation. 1997;95:1686-1744. 2. McGoon et al. Chest. 2004;126:14S-34S.
Echocardiographic Findings that Increase Clinical Suspicion of PVH • Absence of right heart chamber enlargement or pericardial effusion • Evidence of left atrial enlargement • Presence of left ventricular hypertrophy • Impaired diastolic relaxation indices • Elevated left ventricular filling pressures as determined by E/e’ • ratio >15 (most reliable predictor of LA pressure >15 mmHg) • Extent of functional MR and size of mitral valve regurgitant orifice • at rest or during exercise (predictor of increased PA and pulmonary • edema in ischemic heart disease and probably in HFpEF) • Modest elevation of pulmonary pressures (i.e., 60’s rather than > • 80’s)
Findings that Increase the Clinical Suspicion of PVH • Age (elderly) • Female gender • Obesity • Systemic Htn (particularly if not optimally controlled) and LVH • Diabetes mellitus • Coronary artery disease • Obstructive sleep apnea • Atrial fibrillation • EKG findings: • Lack of right axis deviation • Lack of right atrial enlargement or RVH • Evidence of left atrial enlargement • Evidence of left ventricular hypertrophy • Chest X-ray findings: • Pulmonary vascular congestion/ Kerley B lines • Pulmonary edema • Pleural effusion
Progression of RV Dysfunction in PAH Champion H C et al. Circulation 2009;120:992-1007
Estimating Pulmonary Artery Pressures by Echo TR PR TR TR Mean Diast 2* SPAP = 4TR Vmax2 + RAP TR Vmax= Peak TR velocity Diast PA = 4PRend Vmax2 + RAP PRendVmax= End PR velocity Mean PA = TR Vmean+ RAP Or = 4PR Vmax2 + RAP PR Vmax= Peak PR velocity TR Vmean=from VTI Modified from Garvan Kane
Mean Pulmonary Artery pressure • The most reproducible method to estimate mean PA pressure is based on the mean Doppler gradient of the tricuspid regurgitant (TR) signal Mean PA Mean systolic Estimated Pressure RV-RA gradient RA pressure = + Aduen JF, et al. J Am Soc Echocardiogr. 2009: 22; 814-819
Pulmonary Artery Mean and Diastolic Pressures mPAP = 79 – 0.45x (PAAT) = 79 - 0.45x (130) =79-59 = 20 mm Hg mPAP =79 – 0.45x (PAAT) =79- 0.45x (70) = 79 – 32 = 47 mm Hg • PA Diastolic Pressure • [PADP = 4 x (end-diastolic pulmonary • regurgitant velocity)² + RA pressure] • Mean PA Pressure • mPAP = 1/3(SPAP) + 2/3(PADP) • Or 4 x (early PR velocity)² + estimated RA pressure • Or: 0.61 xsPAP + 2 mm Hg ( Chemla’s Equation) • Or: 79 - 0.45 x (PAAT) • Or: 90 – (0.62 x PAAT) • Or mPAP= 80 – 0.5 x (PAAT) • Or: RAP + VTI of TR jet CHEST. 2011;139(5):973-975.
Pulmonary Acceleration Time PV AccT 72 ms mPA = 47 mm Hg Mean PA pressure = 79 - (0.45 x AT)
PA in Pulmonary vascular disease CTEPH- Before PTE Same pt After PTE
Right Atrial Pressure Estimate: IVC and Hepatic Vein Right atrial (RA) pressure estimate should not not be based on an arbitrary value, but rather based on 2D and Doppler imaging of the IVC and hepatic veins* Modified from Garvan Kane *Hepatic veins > 11 mm is abnormal
Right Atrial Pressure Estimate: IVC and Hepatic Vein American Society of Echocardiography Recommends: • 3mmHg, IVC diameter <21mm w/ >50% collapse • 8mmHg, IVC normal in diameter w/ <50% collapse • 15mmHg, IVC diameter >21mm w/ >50% collapse • 20mmHg, IVC dilatation with <50% collapse
Right Atrial Pressure Estimate:Hepatic Vein Flow in PAH Patients • Systolic filling fraction: Vs/ (Vs + Vd) < 55% sensitive and specific for increased RA pressure • Abnormal: A wave is larger than systolic S wave Abnormal A A A D S S D D Abnormal: Vs/Vd< 1 (eg; High RA pressure) Normal: Systolic predominance in hep. vein flow
How should you define mild, moderate, and severe PH? • Not by RVSP • Not by the ratio of RVSP to systemic BP • Define PH severity by the degree of: • RV dilatation • RV dysfunction • RA pressure elevation • Decrease in cardiac index Modified from Garvan Kane
Right Ventricular Afterload RESISTANCE PVR: mean PAP – PCWP = TPG Flow (CO) CO • Reflects the arterial load to steady flow • Doppler correlate: Peak TR pressure gradient / RVOT TVI (although does not incorporate LV filling pressure) Modified from Garvan Kane
PVR PVR = [(TRV/TVIRVOT) x 10] + 0.16 (Abbas Formula)* = (3.9 / 10.2) x10 + 0.16; = 0.38 x10 + 0.16; = 3.8+ 0.16 = 3.98 WU PVRc = (RVSP – E/e’) / VTIRVOT (Corrected Dahiya equation)# *Abbas, AE et al. JACC 2003. 41: 1021-1027 #Dahiya, A et al . Heart 2010. 96: 2005-2009
Right Ventricular Afterload Compliance / Capacitance • Can be estimated by SV / Pulse Pressure (by cath or ECHO) • May be as (more) important in PH as resistance • Pulsatile component of pressure and flow is 30-50% of power transferred from RV to pulmonary bed • Less than 1.0 is abnormal and < 0.8 mL/mm Hg predicts mortality in PAH patients PVCAP = Stroke Volume = LVOT Area x TVI PA Pulse Pressure* 4 (TR Vmax2 – PRendV2) PVCAP = Pulmonary vascular capacitance * PA systolic – PA diastolic Mahapatra, S et al. J. Am Soc Echocardiogr, 2006, 19: 1045-1050
Indirect Echocardiographic Findings in PH • Mean PA pressure : • = 79 - (0.45x PAAT) • Or = 90 – (0.62 x PAAT) • Or =80 – 0.5 x (PAAT) PV AccT 72 ms = 47 mm Hg • RVOT Acceleration time < 90 msec • “Flying W” sign by M-Mode (mid-systolic notching) • Dilated Coronary Sinus Reynolds, BS, RDCS, Terry. The Echocardiographer’s Pocket Reference. Arizona: 2007. Print.
RV Apical 4 Chamber view:Obtain apical long axis views optimized to visualize RV RV centric LV centric
RV Dilatation / LV Compression Flattening / D-shaped Septum RA / RV Morphology in PAH • Apex-forming RV • RAE / IAS Displacement
RV size: Qualitative “Eyeball” Estimate Mild RVE Normal Normal RV Similar to LV/ Shares apex RV 2/3 size of LV Severe RVE Moderate RVE Very large RV/ Apex forming D shaped septum RV Larger than LV
Quantitative Estimate of RV Size • Length (> 86 mm*) • Mid diameter (> 35 mm*) • Basal diameter (>42 mm*) • RV area > 28 cm2* * Measures indicate dilatation • RV end-diastolic diameter has been identified • as a predictor of survival in patients with • chronic pulmonary disease • Tips • Measure at end diastole from an RV • focused apical 4-chamber view • Optimize image to have maximum • diameter without foreshortening the • ventricle LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle. Voekel et al. Circulation. 2006;114:1883-1891. Images courtesy of Kirk Spencer, MD, and Lissa Sugeng, MD, MPH, University of Chicago. Rudski,LG et al. J. Am Soc Echocardiogr 2010.23: 685-713 RVH: RV thickness > 0.5 cm
RV measurements in 2D • RV end-diastolic diameter has been identified as a predictor of survival in patients with chronic pulmonary disease • RV Enlargement: RVD1 > 42 mm or RVD2 > 35 mm or RV Length > 79 mm RV Area > 28 cm2 RVH: RV thickness > 0.5 cm J Am Soc Echocardiogr 2010;23:685-713.
Septal Flattening- Eccentricity Index D1 D2 Eccentricity Index : D1/D2 > 1 In Diastole= volume overload In Systole= volume and pressure overload E.I = 40/25 = 1.6 (D1/D2)
Pericardial Effusion: A bad Sign in PH • Associated with greater disease severity • Increases mortality risk • Likely reflects high venous pressure and poor lymphatics drainage rather than a risk of cardiac tamponade
Echo and RV Function • 3D ECHO might become gold standard • No other valid quantitative assessment of RV function • Subjective evaluation • Tricuspid annular plane systolic excursion (TAPSE) • Tricuspid annulus TDI velocities (S’) • RIMP (Tei Index) • RV area fractional shortening • Dp/dt • RV longitudinal strain measurement • Measurement of cardiac output
Echo measures of RV Function: TAPSE TAPSE • Simple, reproducible • Represents longitudinal function • Correlates well with radionuclide angiography in determining RV systolic function. Relatively load dependent. • Normal > 20 mm. • TAPSE < 18 mm has negative prognostic implications • Angle and load dependent To execute: • In Apical-4 chamber view, place M-Mode cursor through the lateral tricuspid annulus • Measure excursion from end-diastole to end-systole • Average over 3 beats • Off-axis views tend to overestimate TAPSE (as with the apex-forming RV) J Am Soc Echocardiogr 2010;23:685-713., Heart 2006;92:i19-i26 doi:10.1136/hrt.2005.082503
Echo Measures of RV Function:TV annular velocity (S’) by TDI • TV Annular velocity s’ • MPI=(TCO-ET)/ET • Simple, sensitive, reproducible • Good indicator of basal free wall function • By TDI, several indices of RV function can be obtained from a single cardiac cycle • Peak velocities • Isovolumic parameters • Tei index • Angle dependant • Relatively independent of loading conditions • Correlated with RVEF by first pass radionuclide ventriculography • Normal > 10 cm/s • Normal MPI by TDI < 0.55
The RV Index of Myocardial Performance (RIMP) Global Indicator of Systolic and Diastolic Function. • Needs the measurements • of 2 different cardiac cycles • (tricuspid inflow and RV • outflow by PW Doppler) • Normal values below 0.4 • (mean 0.28) • Relatively independent of HR • and from loading conditions • Prognostic in PH • May get pseudonormalized • with high RVDP/ RAP Haddad F et al. Circulation 2008;117:1436-1448 Tei C, et al: J Am Soc Echocardiogr. 1996; 9: 838-847
RV FAC (Fractional Area Change) / Apex-forming RV RV FAC%= 100x RVarea diastole – RVareasystole / Rvareadiastole 27.2 - 21.7 / 27.2 = 20%
Dp/dtRate of rise of LV or RV pressure Normal dp/dt> 400 mm Hg/sec
Prognostic Parameters and Determinants of Risk in PAH Syncope is poor prognostic sign added in the ESC guidelines McLaughlin VV et al. J Am CollCardiol. 2009;53:1573-1619.
Prognostic Value of Echo Parameters of RV Function • 47 pts with PAH • 2-year survival = 88 % if TAPSE > 18 mm • 2-year survival = 50 % if TAPSE < 18 mm • Forfia PR – Am J RespirCrit Care Med 2006; 174: 1034-41 Prognostic Value of MPI Meluzin J – Eur J Echocardiogr 2003; 4: 267-71 Prognostic Value of MPI YeoTc – Am J Cardiol 1998; 81:1157-61 Tei, C- JASE 1996; 9: 838-47 Van Wolferen, SA et al. Eur Heart J (2007) 28, 1250–1257
Kaplan-Meier Survival Curves for Echocardiographic Predictors of Outcomes 81 pts prostacyclinevs placebo F/U 36 months, 20 deaths, 21 transplantations Right atrial area > 20 cm2, abnormal; > 27 cm2 associated with poor prognosis Eccentricity index > 1 abnormal; > 1.7 carries poor prognosis Raymond, R. J. et al. J Am CollCardiol 2002;39:1214-1219
Suggested Assessments and Timing for Follow-ups in patients with PAH: ESC Guidelines