Echocardiography and right heart

catheterization in pulmonary hypertension

Robert NaeijeErasme University Hospital

Brussels, Belgium

Pulmonary Hypertension and Pulmonary Vascular DiseaseEdinburgh, UK, April 26-28, 2007

Right heart catheterization: the gold standard for the diagnosis of

PHPulmonary hypertension is defined by a mean pulmonary artery pressure of > 25 mmHg at rest and > 30 mmHg at exercise (NIH registry)

- Limits of normal of resting mean Ppa 8-20 mmHg- Upper limit of normal of exercise mean Ppa ~40 mmHg (systolic ~65 mmHg)

Naeije R. Pulmonary vascular function. In: Pulmonary Circulation. AJ Peacock and LJ Rubin eds, 2nd ed, Arnold, 2004, chap 1, pp 3-13,

Pra Prv Ppa Ppao

0

Pre

ssur

e, m

mH

g

20

PAH: hemodynamic profile

NIH registryN = 187

IPPHSN = 95

NormalN = 32

Ppa, mmHg 60 ± 18 57 ± 13 8-20

Ppao, mmHg 9 ± 4 9 ± 3 5-14

Pra, mmHg 9 ± 6 11 ± 6 1-9

Q, L/min/m2 2.3 ± 0.9 2.0 ± 1.0 2.5-4.5

PaO2, mmHg

PaCO2, mmHg

70 ± 1330 ± 6

76 ± 2031 ± 5

80-10034-44

Effects of exercise - classical view

An increase in cardiac output during exercise does not greatly affect pulmonary vascular pressures

Typical values for pulmonary vascular pressures and cardiac output at high levels of exercise are Ppa 20-25 mmHg

Ppao 12-15 mmHgQ 20 L/min

AP Fishman, Handbook of Physiology 1985

0 4 8 12 16 20 24 28 320

10

20

30

40

Pulmonary blood flow, l.min-1

Pre

ssur

e, m

mH

g

Ppa

Ppao

Source: Naeije et al J Appl Physiol 1993; 74: 1666-71

Increased pulmonary vascular pressures at high levels of exerciseIncreased pulmonary vascular pressures at high levels of exercise

Limits of normal of pulmonary artery pressures

Review of studies on pulmonary hemodynamics in a total of 91 normal subjects at exercise.

Mean slope of Ppa-Q:1.0 mmHg - L/min in young subjects2.5 mmHg - L/min in old subjectsMean slope of Ppa-Pla:1 mmHg - 1 mmHgFrom Reeves et al.. In: Pulmonary Vascular Physiology

and Pathophysiology. Lung Biology in Health and Disease, Vol 38, Ed Weir and Reeves, Marcel Dekker 1989; chap 4, pp 107-133

PVR = (Ppa - Pla) / Q

Ppa = Q x PVR + Pla

The pulmonary vascular resistance equationThe pulmonary vascular resistance equation

Example: left-to-right shunt-induced pulmonary hypertension

Patient 67 yr with dyspnea and fatigue, pulmonary hypertension and large ASD (echo)

Cath: Qp/Qs = 3.2, Qs = 5 L/min, Ppa 80/15, mean 40 mmHg, Pla 11 mmHg, Pra 10 mmHg, SaO2 95 %

With a normal pulmonary blood flow, Ppa/Q slope 2.5 mmHg/L/min, Ppa = 15 mmHg

Indication for shunt closure, not medical therapy!

PVR = (Ppa – Pla) / Q

PVR calculation rests on the assumptions of linearity and zero crossing

- (Ppa – Pla) /Q relationships are described by a linear approximation over physiological ranges of flows, but present with positive extrapolated pressure intercepts

- PVR therefore is a flow-dependent variable, and better described by a multipoint Ppa/Q relationship

Naeije R. Pulmonary vascular resistance: a meaningless variable? Intens Care Med 2003;29:526-9

Ppa Pla

OutflowInflow

pressurepressure

PcPVR =

Ppa - Pla

Q

1. Linearity2. zero crossing

Ppa-Pla PVR

Q Q

Pc

PVR

Starling resistor modelStarling resistor model

Naeije R, Intens Care Med 2003; 29: 526-9

Improved measurement of PVR

PVR is better defined by measurements of pulmonary artery pressures at several levels of flow, because

- This limits variability related to errors of measurement on both numerator and denominator of just one P/Q ratio

- This allows to defined a more realistic slope of P/Q, which may be different than assumed by PVR calculation

Kafi SA et al, JACC 1998; 31: 1372-6Kafi SA et al, JACC 1998; 31: 1372-6

Ppa/Q plots: exercise vs dobutamine to increase QPpa/Q plots: exercise vs dobutamine to increase Q

Pla = 11 mmHg

Pulmonary artery pressure-flow relations after prostacyclin in PPH Castelain et al, Am J Respir Crit Care Med

2002; 165: 338-40 Ppa/Q relationships before and after 6 wk

iv prostacyclin therapy (11 ± 1.5 ng/kg/min) in 7 PPH patients unresponsive to iNO

Resting hemodynamics unchanged (Ppa 56 to 52 mmHg, Q 2.45 to 2.62 L/min/m2, PVR from 24 to 21 WU, all P NS), but 6 min wk increased by 81 m

Slope of Ppa/Q decreased from 18.2 to 13.1 mmHg/L/min/m2 P < 0.01

0

25

50

75

100

0 1 2 3 4 5 6

y = 7.5 x + 23 r=0.90

y = 12.1 x + 18 r=0.91

Baseline

Prostacycline

Mea

n P

AP

– P

AO

P (

mm

Hg)

Cardiac Index (L/min/m2)

P < 0.01

0

40

80

120

160

Systolic Ppa (mmHg)

0

25

50

75

0 1 2 3 4 5 6

0

25

50

75

100

20

40

60

80

0 1 2 3 4 5

CI(L/min/m2)

BASELINE

PROSTACYCLIN

Mean Ppa - Ppao(mmHg)

Diastolic Ppa (mmHg)

Q

New formula to predict mean Ppa using systolic Ppa

Chemla et al, Chest 2004;126:1313-7

36 patients: 9 IPAH, 7 CTEPH, 6 venous PH, 9 controls

mPpa = 0.61 sPpa + 2 mmHgR2 = 0.98

Ppao?Ppao?Ppw?Ppw?Ppc?Ppc?Pla?Pla?

Left atrial pressure, occluded pressure, wedge pressure,Left atrial pressure, occluded pressure, wedge pressure,and capillary pressure are not equivalentand capillary pressure are not equivalent

stop flowPpao

Ppw

Ppc

Ppa Pla

"occluded" pressure

"wedge" pressure

Arteries VeinsCapillaries

Pre

ssur

e, m

mH

g

Time, seconds

artery capillary vein

Swan-Ganz

Before occlusion

After occlusion

Moment of occlusion

Rapid portion

Inflexion pointSlow portion

Single occlusion for the differential diagnosis between CTEPH, PAH, PVO

Fesler et al, Eur Respir J 2003; 21: 31-6 Fesler et al, Eur Respir J 2003; 21: 31-6

Arterial occlusion for the prediction of postoperative pulmonary hypertension after

pulmonary thrombo-endarteriectomy

Pre-operative partitioning of pulmonary vascular resistance correlates with early outcome following thromboendarterectomy for CTEPH

Kim NH, Fesler P, Channick RN, Knowlton KU, Ben-Yehuda O, Lee SH, Naeije R, Rubin LJ Circulation 2004; 109: 18-22

Occlusion Occlusion

Kim NH, et al. Circulation 2004;109:18-22.

Pre-opPpa 81/33 (50)

fPP 0.96

Post-opPpa 31/11 (21)

∆R 66% rel

Pre-opPpa 84/33 (53)

fPP 0.96

Post-opPpa 86/33 (52)

∆R 26% rel

Patient 1 -- Rup 81% Patient 2 – Rup 52%

Pulmonary artery occlusionWaveform analysis in CTEPH

r = - 0.87

0

500

1000

1500

2000

2500

40 50 60 70 80 90

Rup % pre-PEA

TPRi po

st-P

EACorrelation between pre-op Rup

and post-op TPRi

PEA survivors (23)PEA non-survivors (5)

Kim NH, et al. Circulation 2004;109:18-22

Diagnosis and evaluation of PAH

ABG: arterial blood gasesRHC: right heart catheterisation

I. PH suspicion

II. PH detection

III. PH differentiation

Haemodynamics: RHC + vasoreactivity

Exercise capacity: 6-minute walk test, peak VO2

Blood tests & immunologyHIV testAbdominal ultrasound scan

Pulmonary function tests & ABGVentilation / perfusion lung scanHigh resolution CTSpiral CTPulmonary angiography

ECGChest radiographyTT echocardiography

Symptoms & physical examinationScreening proceduresIncidental findings

ESC Guidelines - Galiè N, et al. Eur Heart J 2004; 25:2243-78.

IV. PAH evaluation

Doppler Echocardiography in Pulmonary Hypertension

• Differential diagnosis: exclusion of mitral and/or aortic valvulopathy, LV systolic/diastolic failure

• Measurement of pressures: maximum velocity of tricuspid regurgitation, acceleration time of pulmonary flow

• Evaluation of right ventricular function: cardiac output, right heart volumes (surface areas), septal displacement (eccentricity index), pericardial effusion, inferior vena cava dimensions and collapsibility, Tei index, TAPSE

• Exercise stress test• Tissue Doppler imaging

Measurement of systolic pulmonary artery pressure from tricuspid

regurgitation

P = 4 x v2

Syst Ppa = P + Pra

m/s

Naeije and Torbicki, Eur Respir J 1995; 8: 1445-1449

Ppa 21/9 mmHg Ppa 74/20 mmHg

Pulmonary Hypertension:Doppler-Echocardiography Definition

Mild pulmonary hypertension is defined as a tricuspid Mild pulmonary hypertension is defined as a tricuspid regurgitant velocity on Doppler echocardiography of regurgitant velocity on Doppler echocardiography of 2.8-

3.4 m/sec which corresponds (assuming a RAP = 5 mmHg) which corresponds (assuming a RAP = 5 mmHg) to a systolic pulmonary artery pressure of to a systolic pulmonary artery pressure of 36-50 mmHg, mmHg,

Venice 3rd World Symposium PAH 2003

Transthoracic echocardiography (TTE): PAP estimate from tricuspid

regurgitation

• High correlation between TTE and RHC measurements of sPAP(0.57–0.93)1

• Moderate agreement

1. Barst RJ, et al. J Am Coll Cardiol 2004; 43:40S-47S.2. Mukerjee D, et al. Rheumatology 2004; 43:461-6.

mPAP (mmHg) at RHC

Tri

cu

sp

id g

rad

ien

t (m

mH

g)

80

1009080706050403020100

0 20 40 60

R2 = 0.4515

RHC = right heart catheterisation

0

20

40

60

80

100

120

0,0 5,0 10,0Cardiac index (l/min/m²)

Cal

cula

ted m

ean P

pa

(mm

Hg)

Healthy subjectSSc-related exercise PAHSevere PAH

Healthy subject - 90W

Systemic sclerosis

(SSc)-relatedexercise PAH

60W

Severe PAH 40W

y = 44.9x - 109

y = 9.9x - 9.5

y = 2.3x+4.8

Stress echocardiography

Measurement of mean pulmonary artery pressure from pulmonary flow waves

AT < 100 ms, AT/ET < 35 %, NR < 50 %, late systolic deceleration of flow

Naeije and Torbicki, Eur Respir J 1995; 8: 1445-1449

AT ET

Ppa 21/9 mmHg Ppa 84/18 mmHg Ppa 62/24 mmHg

TN

NET

NR = TN/NET

A novel echocardiographic predictor of in-hospital mortality and mid-term

hemodynamic improvement after pulmonary endarteriectomy for chronic

thromboembolic pulmonary hypertension. Hardziyenka M et al, Eur Heart J 2007

Time to notching expressed as a notch ratio (NR), or the ratio of time from onset of flow to maximum flow deceleration to time from maximum flow deceleration to end of flow (TN/NET), is associated with in-hospital mortality and increased systolic pulmonary artery pressure at 3 months

The NR is determined by wave reflection Huez S and Naeije R. Reflections about wave reflections

oin CTEPH Editorial, Eur Heart J 2007

Normal Pulmonary hypertension

Tricuspidregurgitation jet

Pulmonaryflow velocity

RV

RARA

RVLVLV

LALA

Tricuspidregurgitation jet

Pulmonaryflow velocity

Doppler-Echocardiography in PAH

Before diuretics, Ppao 28 mmHgBefore diuretics, Ppao 28 mmHg After diuretics, Ppao 13 mmHgAfter diuretics, Ppao 13 mmHg

LV diastolic dysfunction (increased A/E) and eccentricity index (D1<<D2) in severe PAH

D1

D2

2D and Doppler and cardiac catheterization correlates of survival in PPH

(n=26, mean f-up 19.7 months,)

Univariate

severity (none, trace, <1cm, 1-2cm), p = 0.05

Multivariate

severity of effusion – the only independent

predictor of survival

Pericardial effusion (41 Echo/9cath variables)

Eysmann S. Circulation 1989

Raymond RJ et al. J Am Coll Cardiol. 2002;39:1214-1219.

Right Atrial Size Pericardial Effusion LV-Eccentricity Index

RA size < median

RA size > median

No effusion

Effusion

EI < median

EI > median

EI < median

EI > median

No effusion

Effusion

RA size < median

RA size > median

Years Years Years

Sur

viva

l (%

)F

reed

om f

rom

com

posi

te e

nd p

oint

(%

)

0

20

40

60

80

100

0

20

40

60

80

100

0

20

40

60

80

100

0

20

40

60

80

100

0

20

40

60

80

100

0

20

40

60

80

100

0 1 2 3 4 5 0 1 2 3 4 5 0 1 2 3 4 5

0 1 2 3 4 50 1 2 3 4 50 1 2 3 4 5

Echocardiographic Predictors of Adverse Outcomes in PPH

Doppler echocardiographic index for assessment of global right ventricular function

Tei,C.; Dujardin,K.S.; Hodge,D.O.; Bailey,K.R.; McGoon,M.D.; Tajik,A.J.;

Seward,S.B. J Am Soc Echocardiogr, 1996;9:838-47

TR

Tei index

Doppler Echocardiographic Index for Assessment of Global Right Ventricular Function

26 IPAH patients

Index <0.88

60

0

Index >0.88

80

100

40

20

0

10 20 30

Months of follow-up

Alive (%)

Tei C et al. J Am Soc Echocardiogr 1996; 9: 838-847

Tricuspid annular displacement predicts survival in pulmonary

hypertension Forfia et al, Am J Respir Crit Care Med 2006; 174: 1034-41

• Prospective study of 63 consecutive patients with pulmonary hypertension referred for RHC

• Tricuspid annular plane systolic excursion (TAPSE) < 1.8 cm was associated with greater RV dysfunction

• In 47 patients with pulmonary hypertension, 2 tr survival = 88 % if TAPSE > 1.8 cm, 50 % if TAPSE < 1.8 cm

• For everey 1 mm decrease in TAPSE, risk of death increased by 17 %

Forfia et al, Am J Respir Crit Care Med 2006; 174: 1034-41

Importance of IVC and

TDICase report

Man 50 yr, from Brussels to La Paz « alto » (4000 m), in January 2006HAPE on the Ruwenzori in 1988

Several uneventful climbs above 5000 m, up to 6800 mMild headache and fatigue on the Bolivian altiplanoUneventful travel to lake Titicaca (day 3) (4000 m) and

hike to Sajama mountain base camp (day 5) (5200 m)Echocardiography, sea level and days 3 - 5, at 4000 -

4300 m Huez et al, Circulation 2007; 115: 308-309

INFERIOR VENA CAVA PULMONARY DOPPLER TRICUSPID REGURGITANT JET

Sea levelSea level

4000 m, 3 days4000 m, 3 days

4000 m, 5 days4000 m, 5 days

2.7 cm2.7 cm

2.1 cm2.1 cm

ANNULUSBASE APEX

postsystolic shorteningpostsystolic shortening

Circulation 1997; 95: 1479-1486

Hinderliter AL et al. Circulation. 1997;95:1479-1486.

Changes in Echocardiographic Variables by Treatment Group

Right ventricular end-diastolic area (cm2/m) 33 0.4 30 1.6 0.05

Right ventricular % change in area 33 –2.2 30 –2.5 NS

Systolic eccentricity index 32 –0.02 37 0.14 0.02

Diastolic eccentricity index 33 –0.15 37 0.13 0.001

Pericardial effusion size score 36 0 38 0 NS

Tricuspid regurgitant jet area (cm2) 34 0.4 35 1.0 NS

Max tricuspid regurgitant jet velocity (m/s) 32 –0.04 30 0.13 0.01

n nMedian

Change*Median

Change* p

Prostacyclin PlusConventional

Therapy

Conventional Therapy

Alone

J Am Coll Cardiol. 2003;241:1380-1386.

Effects of the Oral Endothelin-ReceptorAntagonist Bosentan on Echocardiographicand Doppler Measures in Patients With Pulmonary Arterial Hypertension

Nazzareno Galiè, MD, Alan L. Hinderliter, MD, Adam Torbicki, MD, Thierry Fourme, MD, Gerald Simonneau, MD, Tomas Pulido, MD, Nilda Espinola-Zavaleta MD, Guido Rocchi, MD, Alessandra Manes, MD, Robert Frantz, MD, Marcin Kurzyna, MD, Sherif F. Naguch, MD, Robyn Barst, MD, Richard Channick, MD, Karl Dujardin, MD, Andrew Kronenberg, MD, Isabelle Leconte, PhD, Maurizio Rainisio, PhD, Lewis Rubin, MD.

Bologna, Italy; Chapel Hill, North Carolina; Warsaw, Poland; Paris, France; Mexico City, Mexico;Rochester, Minnesota; Houston, Texas; New York, New York; San Diego, California; Leuven, Belgium; and Allschwil, Switzerland.

Mean change from baseline to week 16 in results of

RV : LV end-diastolic area

Treatment effect = - 0.64 , p = 0.007

-0.3

-0.2

-0.1

-0.0

0.1

0.2

0.3

0.4

0.5

Bosentan

PlaceboCh

ang

e fr

om

bas

elin

e in

RV

/LV

en

d-d

iast

olic

are

a

Mean change from baseline to week 16 in results of

Doppler RV Index (Tei index)

Treatment effect = -0.06, p = 0.034

DRVI = (TRDUR-RVET)/RVET

TRDUR

RVET

-0.15

-0.10

-0.05

-0.00

0.05 Bosentan (45)

Placebo (26)

Ch

ang

e f

rom

bas

elin

e in

Do

pp

ler

RV

Ind

ex

(mse

c)

Mean change from baseline to week 16 in results of

Pericardial Effusion Size

Treatment effect = -0.54, p = 0.05

-0.25

0.00

0.25

0.50

0.75Bosentan (56)

Placebo (29)

Ch

ang

e f

rom

bas

elin

e in

Pri

card

ial e

ffu

sio

n s

ize

(n)

Absent=0

Trace=1

Small=2

Moderate=3

Large=4

Mean p†

RV end-diastolic area–cm2 -1.81 0.122

RV end-systolic area–cm2 -2.32 0.057

RV percent change in area–% 4.84 0.094

LV end-diastolic area–cm2 4.19 0.003

LV end-systolic area–cm2 2.70 0.016

LV systolic eccentricity index -0.12 0.047

LV diastolic eccentricity index -0.07 0.174

RV:LV diastolic areas ratio -0.64 0.007

IVC minimum diameter – cm -0.22 0.033

Pericardial effusion score - % -17‡ 0.053

Mean p†

RV acceleration Time–msec 5.87 0.169

RV ejection time–msec 22.15 0.007

Doppler RV index -0.06 0.034

TV reg velocity–cm/sec -10.90 0.280

LV stroke volume – ml 7.37 0.007

Heart Rate – b/min -2.31 0.118

Cardiac Index – l/min/m2 0.37 0.007

MV peak E vel – cm/sec 10.45 0.003

MV E/A ratio 0.18 0.004

MV Time-vel integral – cm 2.34 0.001

> 80% feasibility

Mean change from baseline to week 16 in results of

Echocardiographyc and Doppler parameters

P0.05

Conclusions

• Right heart catheterization remains the gold standard of diagnosis in pulmonary hypertension – measurements can be refined by partitioning of PVR and exercise stress

• Doppler echocardiography is essential in screening, differential diagnosis, and follow-up of pulmonary hypertension

The procedure must be seen as an extension of the clinical examination, not a source of magic numbers

A Boonstra