Ipertensione polmonare Eco e diagnosi: vantaggi, limiti, errori evitabili Michele D’Alto mic.dalto@tin.it UOC Cardiologia II Università degli Studi, A.O. “V. Monaldi” - Napoli

Pulmonary hypertension: general definitions 2009

Pulmonary hypertension: haemodynamic definition 2009

WHO classification of pulmonary hypertension Venice 2003 revised Dana Point 2008 1. Pulmonary arterial hypertension Idiopathic PAH Heritable PAH (BMPR2, ALK1..) Drugs and toxins Associated with CTD, HIV, portal hypertension, congenital heart diseases, chronic hemolytic anemia (SSD) and shistosomiasis PPHN 1’ PVOD, PHCM 2. PH with left heart disease Systolic dysfunction Diastolic dysfunction Valvular 3. PH with lung diseases/hypoxemia COPD Interstitial lung diseases Sleep-disordered breathing Altitude exposure Alveolar hypoventilation Developmental abnormalities 4. CTEPH No more distinction proximal/distal 5. Miscellaneous Sarcoidosis, histiocytosis X, Gaucher,..

Normal estimated PAPs value at echo? 37 mmHg, but…

Echocardiography for PH diagnosis: pitfalls TVR Poor Doppler signal Uncertain TVR peak Theta angle RV systolic pressure estimation Simplified Bernoulli ΔP = 4 (V)2 TVR (simplified Bernoulli) + RAP estimation Arbitrary From ICV to… RAP

Echocardiography, age and body size Circulation 2001;104: 2797–802 J Am Coll Cardiol 2009;54:S55–66 3790 “normal” subjects (1358 M, 2432 F) from 1 to 89 years. PASP calculated by modified Bernoulli equation, with RAP assumed to be 10 mmHg. +10

Echocardiography, age and body size Circulation 2001;104: 2797–802

Echocardiography for PH in SSc Arthritis Rheum 2005;52(12):3792-3800 - 21 SSc expert centers - 599 SSc patients (-29 known PAH = 570) Reliability of prospective screening of SSc patients based on: TVR >2.5 m/s in symptomatic patients or TVR >3.0 m/s irrespective of symptoms. 33 patients 45% of cases of echocardiographic diagnoses of PH were falsely positive!

Echocardiography for PH in SSc Rheumatology 2004; 43:461-6 137 SSc pts studied false pos echo false neg cath

Estimated right atrial pressure Systolic PAP = RV-RA gradient + RAP ICV < 15mm collasso RAP 0-5 mmHg ICV 15-25mm rid. >50% RAP 5-10 mmHg ICV >25mm rid. <50% RAP 10-15 mmHg ICV >25mm+v.sovr. No rid. RAP 20 mmHg Mod from Otto CM, 2002

Estimated right atrial pressure Echocardiography for PH in HIV Am J Respir Crit Care Med 2009;179:615–621 65 HIV pts studied Estimated right atrial pressure IVC <20mm Collaps >50% IVC <20mm Collaps <50% IVC >20mm Collaps >50% IVC >20mm Collaps <50%

Echocardiography 65 HIV pts studied Good quality Doppler Am J Respir Crit Care Med 2009;179:615–621 65 HIV pts studied Good quality Doppler Poor quality Doppler 95% limits of agreement: +38.8 and -40.0 mmHg

additional echo variables 2009 PH possible: PASP 37-50 mmHg (TVR 2.9-3.4 m/s) additional echo variables PH likely: - PASP >50 (TVR > 3.4 m/s)

Echocardiography Direct PH signs Indirect PH signs PASP > 37 (50) mmHg Increased velocity PV reg (mPAP) Short acc. time in RVOT (mPAP) Right heart dilation Flat IV septum (LV EI <0.8) Increased RV wall thickness 2009

Indirect PH signs: PAPm 79 - 0.45 • (AcT) PAPm = 79 - 0.45 • 44.3 = 79 - 20 = 59 PAPm = 57 Mean PAP

Indirect PH signs: Right heart (and PA) dilation 57 mm Ao PA

Right atrium: and PAH cm2/m (area/altezza) Raymond, RJ, J Am Coll Cardiol 2002;39:1214–9

Right atrium size Normal value: <16 cm2 <9 cm2/m <40 ml <20 ml/m2 Raymond RJ, J Am Coll Cardiol 2002;39:1214–9 Wang Y, Chest 1984;86:595-601

Indirect PH signs: flat IV septum, hypertrophic RV wall Left ventricular (LV) eccentricity index (EI): D2/D1 in short axis view (normal value = 1) D2 D1 LV RV EI = 0.65

What determines PAPm? PVR = ΔP / Q PVR PVR = (PAPm – PWP) / Q ΔP Q PVR X Q = PAPm – PWP PVR X Q + PWP = PAPm High output LV dysfunction PAH

Three different conditions with high estimated PAPm (PVR X Q) + PWP = PAPm PAH High output LV dysfunction Argiento, Eur Respir J 2009

Assessment of LV filling pressures PCWP = 1.9 + (1.24 x E/Ea) NO PAH or very end-stage Normal LV filling pressure Precapillary PH first diagnosis 9/60 (15%) mistakes Nagueh et al. JACC 1997 & Circulation 2000

Midsystolic pulmonary artery notching = High PVR Rats were treated with monocrotaline for: 0 (A), 15 (B), 22 (C), 37 (D) days. 0 d monocrotaline 15 d monocrotaline Midsystolic pulmonary artery notching. Rats were treated with monocrotaline (MCT) for 0 (A), 15 (B), 22 (C), and 37 (D) days. Pulse-wave Doppler of pulmonary outflow was recorded in the parasternal view at the level of the aortic valve. Sample volume was placed (5 mm) proximal to the pulmonary valve leaflets and aligned to maximize laminar flow. Note the early notching at day 15 (B) and its subsequent progression. 22 d monocrotaline 37 d monocrotaline Jones J E, Am J Physiol Heart Circ Physiol 2002;283:364-71

Midsystolic pulmonary artery notching = High PVR Normal High PVR Very high PVR

Midsystolic pulmonary artery notching = High PVR Why? = reverse wave for high PVR

Pre-test probability: the Bayes’ theory The probability of an event A given an event B (e.g., the probability of CAD given a positive stress test) depends not only on the relationship between events A and B (i.e., the accuracy of stress test) but also on the marginal probability (or "simple probability") of occurrence of each event in a specific population. Rev. Thomas Bayes, 1763 Stress test for CAD detection: - CAD prevalence in group A = 50%; test + = 82% CAD - CAD prevalence in group B = 3%; test + = 13% CAD

Population at risk for PAH J Am Coll Cardiol 2008;51:1527–38 Relatives of IPAH patients Associated condition for PAH Connective tissue disease (CREST* 30%, SSc 10%) 10-15% Portal hypertension 1-6% HIV infection 0.5-1% Anorexigen drugs 0.006-0.01% Unoperated shunt 5-10% *CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia)

Pre-test probability of precapillary PH 2009

Pre-test probability of pre-capillary PH high RA > LA RV > LV D-shaped LV

Pre-test probability of pre-capillary PH low RA < LA RV < LV Normal shaped LV

PAH RV adaptation to pressure overload RV hypertrophy and progressive dilatation Tricuspid regurgitation and RA dilatation Paradoxical septal motion and altered LV filling Diastolic and systolic RV dysfunction Pericardial effusion in the more severe cases LV dysfunction Haddad et al. Circulation 2008

PAH PVH Pulmonary arterial or venous hypertension? RV dilation/hypertrophy LV dilation/hypertrophy RA enlargement LA enlargement E/A <1 (mild diastolic dysf) E/A >1 (pseudonorm/restr) PAH predisposing condition Left heart disease D-shape LV Normal LV shape PA notch No PA notch PAH PVH Group 1 Dana Point Group 2 Dana Point

Take-at-home message ECHO The gold standard for PAH diagnosis remains right heart catheterization! Echo plays a key-role in screening, differential diagnosis and follow-up. ECHO Echo does not provide “magic numbers”: multi-parametric evaluation! It is mandatory to evaluate the PAH “pre-test probability”. It is strongly encouraged a deep knowledge of PAH pathophysiology (echo as part of clinic evaluation!).