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1 Cardiac Catheterization is Cardiac Catheterization is Unnecessary in the Evaluation of Unnecessary in the Evaluation of Patients with Pulmonary Patients with Pulmonary Hypertension: Hypertension: CON CON Dunbar Ivy, MD Dunbar Ivy, MD The Children The Children’ s Hospital Heart Institute s Hospital Heart Institute 2 Diagnostic Evaluation: Right Heart Cardiac Catheterization Gold Standard’ Establish diagnosis Ascertain etiology Evaluate vasoreactivity Establish severity & prognosis Guide treatment McGoon M, Gutterman D, Steen V, et al. Chest 2004;126;14S-34S

Cardiac Catheterization is Unnecessary in the … Catheterization is Unnecessary in the Evaluation of Patients with Pulmonary Hypertension: CON ... Right Heart Cardiac Catheterization

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Cardiac Catheterization is Cardiac Catheterization is Unnecessary in the Evaluation of Unnecessary in the Evaluation of

Patients with Pulmonary Patients with Pulmonary Hypertension:Hypertension:

CONCON

Dunbar Ivy, MDDunbar Ivy, MDThe ChildrenThe Children’’s Hospital Heart Institutes Hospital Heart Institute

2

Diagnostic Evaluation:Right Heart Cardiac Catheterization

‘Gold Standard’

• Establish diagnosis

• Ascertain etiology

• Evaluate vasoreactivity

• Establish severity & prognosis

• Guide treatment

McGoon M, Gutterman D, Steen V, et al. Chest 2004;126;14S-34S

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Pulmonary Arterial HypertensionPulmonary Arterial Hypertension

•• Sustained elevation of mean pulmonary Sustained elevation of mean pulmonary arterial pressure to > 25 mm Hg, with a arterial pressure to > 25 mm Hg, with a mean pulmonary capillary and left atrial mean pulmonary capillary and left atrial pressure < 15 mm Hg at rest pressure < 15 mm Hg at rest

–– Pulmonary Vascular resistance > 3 Units Pulmonary Vascular resistance > 3 Units X mX m22

Simonneau G, et al. J Am Coll Cardiol 2009;54:S43-S54

Echo Doppler Estimate of PA pressure

Limitations of Doppler Estimate of PA Systolic Pressure

• Requires a good acoustic window

• Requires a good and properly aligned Doppler signal

• Tricuspid regurgitation has to be present

• Can be affected by incorrect assumption of right atrial pressure

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Pulmonary Vein Stenosis IN BPD

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Pulmonary Vein Stenosis

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Diagnostic Evaluation:Right Heart Cardiac Catheterization

‘Gold Standard’

• Establish diagnosis

• Ascertain etiology

• Evaluate vasoreactivity

• Establish severity & prognosis

• Guide treatment

McGoon M, Gutterman D, Steen V, et al. Chest 2004;126;14S-34S

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What Is the Cause of Pulmonary Hypertension?

2

VCVC RARA RVRV PAPA PVPVPCPC

LALA LVLV AoAo

PostPost--Capillary PH Capillary PH (PCWP>15 (PCWP>15 mmHgmmHg; PVR ; PVR nlnl))

Systemic HTNSystemic HTNAoVAoV DiseaseDisease

Myocardial DiseaseMyocardial DiseaseDilated CMPDilated CMP--ischemic/nonischemic/non--iscisc..

HypertrophicHypertrophic CMPCMPRestrictive/infiltrative CMPRestrictive/infiltrative CMP

Obesity and othersObesity and others

AtrialAtrial MyxomaMyxomaCorCor TriatriatumTriatriatum

PV PV compression compression

PVODPVOD

PAHPAHRespiratoryRespiratory

DiseasesDiseasesPEPE

PulmonaryPulmonary Hypertension:Hypertension: TypesTypes

MV DiseaseMV Disease

↑↑LVEDPLVEDP

PrePre--capillary PH (PAH)capillary PH (PAH)PCWPPCWP<<15 15 mmHgmmHgPVR PVR >> 3 Wu3 Wu

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BPD and PAH

Mourani, Ivy, Rosenberg, Fagan, Abman. J Peds 2008;152:291-293

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Diagnostic Evaluation:Right Heart Cardiac Catheterization

‘Gold Standard’

• Establish diagnosis

• Ascertain etiology

• Evaluate vasoreactivity

• Establish severity & prognosis

• Guide treatment

McGoon M, Gutterman D, Steen V, et al. Chest 2004;126;14S-34S

Treatment Overview

Barst R, et al. J Am Coll Cardiol 2009;54:S78-S84

Incomplete response

Yes No

Incomplete response

Incomplete response

Incomplete response

Incomplete response

Yes

No

Calcium Channel Blocker

Conventional treatment

Acute vasodilator response

Responder Non Responder

Right heart failure

Bosentan oralSildenafil oralTadalafil oral

Iloprost inhaledTreprostinil sc

Treprostinil inhaled

Combination of drugs

IV prostanoids (Epoprostenol, Treprostinil) 

Atrial septostomy

Transplantation

Tissot, Ivy, Beghetti

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Pulmonary Vascular Pulmonary Vascular Reactivity TestingReactivity Testing

•• Acute response Acute response -- ClassicClassic-- Decrease in mPAP of at least 20% Decrease in mPAP of at least 20% -- with the PVR decreasing with the PVR decreasing 20%20%-- with no change or an increase inwith no change or an increase incardiac outputcardiac output

••Acute response Acute response --RevisedRevised-- Decrease in mPAP of at least 10 mmHg Decrease in mPAP of at least 10 mmHg -- with the mPAP decreasing with the mPAP decreasing ≤≤ 40 mmHg 40 mmHg -- with a normal or high cardiac outputwith a normal or high cardiac output

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Diagnostic Evaluation:Right Heart Cardiac Catheterization

‘Gold Standard’

• Establish diagnosis

• Ascertain etiology

• Evaluate vasoreactivity

• Establish severity & prognosis

• Guide treatment

McGoon M, Gutterman D, Steen V, et al. Chest 2004;126;14S-34S

HemodynamicsHemodynamics——NIH RegistryNIH Registry

4

Freq

uenc

y

Right Atrial Pressure (mm Hg)

30

20

10

08 12 16 20 24 28

Normal Range

1

Freq

uenc

y

Cardiac Index (L/Min/M2)

50

30

100

40

20

2 3 4 5 6 7 8

Normal Range

20 60 80

50

Freq

uenc

y

Mean Pulmonary Artery Pressure(mm Hg)

4030

20

10

040 100 120

Normal Range

10 40 50

30

Freq

uenc

y

Pulmonary Vascular Resistance Index(L/Min/M2)

25201510

030 70 80

5

20 60 90

Normal Range

Rich S et al. Ann Intern Med. 1987;107:216-223.

Hemodynamic Predictors of Survival in Patients With PPH: A National

Prospective Registry

D’Alonzo GE, et al. Ann Intern Med. 1991;115:343-349.

Variable Odds Ratio (95% CIs)Right atrial pressure (mean) 1.99 (1.47 – 2.69)

Pulmonary arterial pressure (mean) 1.16 (1.05 – 1.28)

Cardiac index 0.62 (0.46 – 0.82)

PAH Determinants of Risk

McLaughlin VV and McGoon MD. Circulation, In press.

Determinants of RiskDeterminants of Risk Lower RiskLower Risk Higher RiskHigher Risk

Clinical evidence ofRV failure No Yes

Progression Gradual Rapid

WHO class II, III IV

6MW distance Longer (>400 m) Shorter (<300 m)

BNP Minimally elevated Very elevated

Echocardiographic findings Minimal RV dysfunction

Pericardial effusion,significant RV dysfunction

Hemodynamics Normal/near normalRAP and CI High RAP, low RAP

Sitbon O et al. J Am Coll Cardiol. 2002;40:780-788.

Predictors of Outcome on EpoprostenolVariables

Hazard Ratio (95% CI) p value

Age >44 yrs 1.17 (0.71-1.94) 0.535

Gender (female/male) 0.95 (0.53-1.71) 0.877

Anorexigenic (yes/no) 0.95 (0.55-1.65) 0.853

Raynaud’s phenomenon(presence/absence) 1.38 (0.72-2.65) 0.334

History of syncope (yes/no) 0.75 (0.44-1.25) 0.226

History of right-sided heart failure (yes/no) 2.19 (1.31-3.64) 0.003

NYHA FC IV vs III 2.24 (1.34-3.73) 0.002

Six-minute walk distance ≤250 m 2.20 (1.31-3.69) 0.003

Baseline hemodynamicsmRAP ≥12 mm HgmPAP <65 mm HgPAOP ≥10 mm HgCI ≤1.80 L/min/m2

TPR ≥35.4 U/m2

mSAP ≤93 mm HgHeart rate ≤88 beats/minSystolic index ≤21.4 mL/m2

Svo2 ≤54.5%

2.74 (1.58-4.75)1.72 (1.04-2.86)0.87 (0.51-1.50)0.96 (0.58-1.59)0.65 (0.39-1.09)1.24 (0.71-2.18)0.76 (0.43-1.34)1.46 (0.83-2.58)1.54 (0.93-2.56)

0.00030.0360.6230.8790.1020.4490.3490.1730.096

VariablesHazard Ratio

(95% CI) p value

NYHA FC III/IV vs I/II 8.75 (4.58-16.7) <0.0001

Six-minute walk distance <380 m 2.62 (1.45-4.74) 0.001

Increaase in distance walked <112 m from baseline 1.09 (0.61-1.96) 0.759

Dose of epoprostenol achieved <14 ng/kg/min 0.60 (0.33-1.08) 0.086

mRAP >10 mm Hg 3.57 (1.65-7.71) 0.001

mPAP <59 mm Hg 1.94 (1.06-3.55) 0.032

Decrease in mPAP ≥10% relative to baseline 1.25 (0.69-2.27) 0.462

CI ≤2.4 L/min/m2 1.45 (0.79-2.66) 0.231

Increase in CI <0.5 L/min/m2 relative to baseline

2.35 (1.23-4.52) 0.010

TPR ≥25 U/m2 1.53 (0.82-2.85) 0.185

Decrease in TPR <30% relative to baseline 1.90 (1.02-3.54) 0.041

Svo2 <62% 2.64 (1.41-4.95) 0.002

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Diagnostic Evaluation:Right Heart Cardiac Catheterization

‘Gold Standard’

• Establish diagnosis

• Ascertain etiology

• Evaluate vasoreactivity

• Establish severity & prognosis

• Guide treatment

McGoon M, Gutterman D, Steen V, et al. Chest 2004;126;14S-34S

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Guide Treatment:

• Epoprostenol dosing

• Timing of listing for lung transplantation

• Timing for addition or change of therapy

• Performance of atrial septostomy