Pulmonary hypertension with cardiac shunt determination

PULMONARY HYPERTENSION AND CARDIAC SHUNT DETERMINATION

DR. RAJESH DAS

PULMONARY HYPERTENSIONOVERVIEW

Definitions Pathogenesis Classification Diagnosis

IMPORTANT DEFINITIONS

Pulmonary hypertension (PH) is a haemodynamic and pathophysiological

condition defined as an increase in mean pulmonary arterial pressure (PAP) ≥25 mmHg at rest as assessed by right heart catheterization.

The definition of PH on exercise as a mean PAP .30 mmHg as assessed by RHC is not supported by published data and healthy individuals can reachmuch higher values.

European Heart Journal (2009) 30, 2493–2537

HAEMODYNAMIC DEFINITIONS OF PULMONARY HYPERTENSION




THE EXACT PROCESS IS STILL UNKNOWN!!

MOLECULAR ABNORMALITIES IN PAH Prostacyclin

vasodilator, inhibits platelet activation, antiproliferative properties,Prostacyclin synthase is decreased in the pulmonary arteries in PAH.

Endothelin-1 Potent vasoconstrictor and stimulates PASMC

proliferation.Plasma levels of ET-1 are increased in PAH and clearance is reduced.

Nitric Oxide. Vasodilator, inhibitor of platelet activation Inhibition of vascular smooth-muscle cell

proliferation.Impaired production of NO is seen in PAH.

Serotonin (5-HT) vasoconstrictor and promotes PASMC hypertrophy

and hyperplasia.Allelic variation in serotonin transporter(SERT) present in PAH.

Vasoactive intestinal peptide (VIP) has a pharmacologic profile similar to prostacyclins.

Serum and lung tissue VIP levels are decreased in PAH patients

GENETICS OF PAH Bone Morphogenetic Protein Receptor 2

Gene(BMPR2) belong to the TGF-b superfamily involved in the

control of vascular cell proliferation. mutations are detected in at least 75% of cases

PAH occurs in a familial context. Mutations of this gene can also be detected in 25%

of apparently sporadic cases.

Activin Receptor-like Kinase 1 And Endoglin PAH associated with HHT.

PATHOGENESIS OF PAH

Gaine S. J Am Med Assoc 2000;284:3160-68



CLASSIFICATION OF PULMONARY HYPERTENSION

First attempt in 1973 meeting organized by the WHO. A distinction was made between primary

and secondary PH

The Dana Point 2008 4th World Symposium on PH Based on shared pathologic, pathobiologic,

and clinical features.

UPDATED CLINICAL CLASSIFICATION OF PULMONARY ARTERIAL HYPERTENSION (DANA POINT, 2008)

1 Pulmonary arterial hypertension (PAH)

1.1 Idiopathic

1.2 Heritable 1.2.1 BMPR2 1.2.2 ALK1, endoglin

(with or without hereditary haemorrhagic telangiectasia)

1.2.3 Unknown

1.3 Drugs and toxins induced

1.4 Associated with (APAH) 1.4.1 Connective tissue diseases 1.4.2 HIV infection 1.4.3 Portal hypertension 1.4.4 Congenital heart disease 1.4.5 Schistosomiasis 1.4.6 Chronic haemolytic anaemia

1.5 Persistent pulmonary hypertension of the newborn

1’ Pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis

J Am Coll Cardiol 2009;54:S43–S54.


2. Pulmonary hypertension due to left heart disease 2.1. Systolic dysfunction 2.2. Diastolic dysfunction 2.3. Valvular disease

3. Pulmonary hypertension due to lung diseases and/or hypoxia 3.1. Chronic obstructive pulmonary disease 3.2. Interstitial lung disease 3.3. Other pulmonary diseases with mixed restrictive and obstructive pattern 3.4. Sleep-disordered breathing 3.5. Alveolar hypoventilation disorders 3.6. Chronic exposure to high altitude 3.7. Developmental abnormalities


4. Chronic thromboembolic pulmonary hypertension (CTEPH)

5. PH with unclear multifactorial mechanisms 5.1. Hematologic disorders: myeloproliferative disorders splenectomy.

5.2. Systemic disorders, sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis

5.3. Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders

5.4. Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis

EPEDIOMOLOGY

Commonest cause of PH in adults is COPD.

Estimated incidence of IPAH is 1-2 newly diagnosed cases per million people per year.

Prevalence of PAH in adult CHD- 5–10%, out of which 25- 50% presenting with ES.

Rev Esp Cardiol. 2010 Oct;63(10):1179-93

http://www.ncbi.nlm.nih.gov/pubmed/20875358





PH WITH CARDIAC SHUNT

PAH associated with CHD is included in group 1 of the PH clinical classification.

Persistent exposure of the pulmonary vasculature to increased blood flow may result in a typical pulmonary obstructive arteriopathy (identical to other PAH forms) that leads to the increase of PVR.

Rev Esp Cardiol. 2010 Oct;63(10):1179-93






CLINICAL CLASSIFICATION OF CONGENITAL SYSTEMIC-TO-PULMONARY SHUNTS ASSOCIATED WITH PAH

A. Eisenmenger’s syndrome ES includes all systemic-to-pulmonary shunts due to

large defects leading to a severe increase in PVR and resulting in a reversed or bidirectional shunt.

Cyanosis, erythrocytosis, and multiple organ involvement are present.

B. PAH associated with systemic-to-pulmonary shunts

In these patients with moderate to large defects, the increase in PVR is mild to moderate, systemic-to-pulmonary shunt is still largely present.

no cyanosis is present at rest.European Heart Journal (2009) 30, 2493–2537

C. PAH with small defects usually VSD<1 cm and ASD<2 cm of effective

diameter assessed by echocardiography. clinical picture similar to idiopathic PAH.

D. PAH after corrective cardiac surgery PAH is either still present immediately after surgery

or has recurred several months or years after surgery in the absence of significant post-operative residual congenital lesions.


CLINICAL CLASSIFICATION OF CONGENITAL SYSTEMIC-TO-PULMONARY SHUNTS ASSOCIATED WITH PAH



WHEN SHOULD THE DIAGNOSIS OFPAH BE CONSIDERED?

Patients with unexplained exercise limitation

Patients with clinical signs consistent with right heart dysfunction

Patients with abnormal right ventricular findings on radiography, echocardiography or electrocardiography

Patients with systemic disease known to be associated with PAH

SYMPTOMS ASSOCIATED WITH PAH

Shortness of breath Syncope Chest pain Symptoms of RH dysfunction

BreathlessnessAscitesAnkle swellingAnorexia

SIGNS ASSOCIATED WITH PAH

Loud split P2 RV hypertrophy Increased “a” waves Increased “v” waves Diastolic murmur (PR) Pansystolic murmur (TR)

SIGNS OF RH FAILURE

Poor peripheral perfusion Raised RA pressure RV 3rd and 4th heart sounds Tricuspid regurgitation Ejection systolic murmur across the

pulmonary valve

WHO CLASSIFICATION OF FUNCTIONAL STATUS OF PATIENTS WITH PH

DIAGNOSIS OF PH WITH CARDIAC SHUNTS

The signs and symptoms of Eisenmenger’s syndrome result from PH, low arterial O2 saturation, and secondary erythrocytosis.

They include dyspnoea, fatigue, and syncope.

haemoptysis, cerebrovascular accidents, brain abscesses, coagulation abnormalities, and sudden death.

PULMONARY ARTERIAL HYPERTENSION: CLINICAL COURSE AND PROGRESSION

CLEVELAND CLINIC JOURNAL OF MEDICINE 2007. 74(10)

DIAGNOSTIC ALGORITHM FOR PAH


Contd on next slide

DIAGNOSTIC ALGORITHM FOR PAH CONTD..


FINDINGS ON ELECTROCARDIOGRAM

• Highly specific but not very sensitive. • RVH, RAE, RAD, RBBB.

FINDINGS IN PH CHEST RADIOGRAPHY

Cardiac enlargement

Prominent proximal PA

“Pruning” of distal PA

ECHOCARDIOGRAPHY IN PAH

T R RVE RAE RVH Flattening of IVS Dilated IVC

VENTILATION PERFUSION LUNG SCAN

IPAH CTEPH

CT FEATURES OF PULMONARY HYPERTENSION

Wall-adherent thrombotic material in pulmonary arteries CTEPH Severe idiopathic pulmonary arterial hypertension

Calcifications in pulmonary arteries CTEPH Longstanding severe pulmonary hypertension Eisenmenger syndrome

Peripheral pulmonary arteriovenous shunting Portopulmonary hypertension Hepatopulmonary syndrome

Pulmonary vascular dilatation (central or peripheral) Left-to-right shunt

RadioGraphics 2010; 30:1753–1777

MAGNETIC RESONANCE IMAGING (MRI)

Useful for Assessment of congenital heart diseases in children and adults:

visceral-atrial situs,

connection and course of great veins and arteries,

Hidden septal defects (sinus venosus ASD and supracristal, or posterior ventricular septal defects)

above all, assessment of the size and function of the cardiac chambers, and in particular the right ventricle

Rev Esp Cardiol. 2007;60(9):895-8

GENETIC TESTING

Genetic testing and professional genetic counseling should be offered to relatives of patients with FPAH.

CHEST 2007; 131:1917–1928

6 MINUTE WALK TESTING

In patients with PAH, serial determinations of functional class and exercise capacity assessed by the 6 minute walk test provide benchmarks for disease severity, response to therapy, and progression.

CHEST 2007; 131:1917–1928

TRANSESOPHAGEAL ECHOCARDIOGRAPHY (TEE)

Useful in detection of intracardiac shunts, especially ASD and detect central pulmonary emboli

CHEST 2007; 131:1917–1928

PULMONARY ANGIOGRAPHY

In patients with PAH and a V/Q scan suggestive of CTEPH, pulmonary angiogram is required for accurate diagnosis and best anatomic definition to assess operability.

CHEST 2007; 131:1917–1928

RIGHT HEART CATHETERIZATION

-CONFIRMATION OF DIAGNOSIS -EXCLUSION OF OTHER CAUSES -ESTABLISH SEVERITY -ASSEMENT OF PROGNOSIS -ASSESMENT OF PULMONARY VASOREACTIVITY: challenge with inhaled NO, intravenous

epoprostenol or intravenous adenosine. Positive Response:

>10mm mean PAP decrease and < 30mmHg final mean PAP > 33% decrease in PVR, ideally to < 6 units. Unchanged or increased CI

CHEST 2007; 131:1917–1928

PROGNOSIS

NATURAL HISTORY AND SURVIVAL

INTRACARDIAC SHUNT ESTIMATION

INTRACARDIAC SHUNTS

Left-to-right shunt

Right-to-left shunt

Bidirectional shunt

WHEN TO SUSPECT DURING CATHETERIZATION?

unexplained pulmonary artery oxygen saturation exceeding 80%(? Left-Right shunt)

unexplained arterial desaturation <95% (Right- left shunt)

Arterial desaturation commonly results from alveolar hypoventilation and associated physiological shunting oversedation from premedication, pulmonary disease, pulmonary venous congestion, pulmonary edema, cardiogenic shock.

METHODS TO ESTIMATE SHUNTS

Cardiac CatheterisationOximeric methodIndicator dilution method

Echocardiography

PRINCIPLES OF THE OXYMETRIC METHOD

Blood Sampling from various chambers to determine Oxygen Saturation.

Left to Right Shunt is present when a significant increase in blood oxygen saturation is found between 2 right sided vessels or chambers.

OXIMETRIC METHOD

A “screening” oxygen saturation measurement is done by sampling of blood in the SVC and the pulmonary artery.

If the difference is 8% or more, a left-to-right shunt may be present, and an oximetry “run” is performed.

OXIMETRIC RUN

Obtain a 2-ml sample from each of the following locations: 1. Left and or right PA.

2. Main PA.

3. RVOT.

4. RV-mid

5. RV-tricuspid valve or apex

6. RA- low or near tricuspid valve

7. RA- mid

8.RA- high

9. SVC- low (near junction with right atrium)

10. SVC- high (near junction with innominate vein)

11. IVC- high (just at or below diaphragm)

12. IVC- low L4-L5)

13. LV

14. Aorta(distal to insertion of ductus )

OXIMETRIC RUN

For localizing Right to Left Shunts one should also obtain samples from…. Pulmonary Vein Left Atrium Left Ventricle Distal Aorta

OXIMETRY RUN

A significant step-up is defined as an increase in blood oxygen content or saturation that exceeds the normal variability that might be observed if multiple samples were drawn from that cardiac chamber.

O2 content (ml/L)= SpO2 × 1.36 (ml/g) × Hb (g/dL) × 10

1 vol% = 1ml O2/100ml blood or 10 ml O2/L

OXIMETRY RUN

Dexter Criteria: significant step-up in oximetry run :

Right Atrium: Highest O2 content in blood samples drawn from the RA exceeds the highest content in the venae cavae by 2 vol % .

Right ventricle: If the highest RV sample is 1 vol % higher than the highest RA sample.

Pulm. artery: the PA oxygen content is more than 0.5 vol% greater than the highest RV sample.

OXIMETRY RUN In an anemic or polycythemic patient step-up in

percentage oxygen saturation is better.

Oxygen Saturation Values for Shunt Detection:

a Difference distal- proximal chamber.

QUANTIFICATION OF SHUNT

FICK EQUATION The principles used

to determine Fick cardiac output are also used to quantify intra-cardiac shunts.

Flow= Oxygen consumption/Arterial-Venous oxygen content difference.

O2 consumption is assumed based on patient’s age, gender and body surface area when not directly measured.

CALCULATION OF PULMONARY BLOOD FLOW (QP)

CALCULATION OF SYSTEMIC BLOOD FLOW (QS)

WHAT IS MIXED VENOUS O2 CONTENT?

The MVO2 (mixed venous oxygen content) is the average oxygen content of the blood in the chamber proximal to the shunt.

When assessing a left-to-right shunt at the level of the RA, mixed venous oxygen content is calculated by the Flamm formula: MVO2 = 3(SVC O2 content) + (IVC O2 content)

4

CALCULATION OF BIDIRECTIONAL SHUNTS

Effective blood flow: the flow that would exist in the absence of any left-to-right or right-to-left shunting:

L → R shunt = PBF – SBF (Or Qp – Qs)

Bidirectional shunts: L → R shunt = PBF – EBF (or Qp – QEP)

R → L shunt = SBF – EBF (or Qs – QEP)

SHUNT CALCULATION

CLINICAL SIGNIFICANCE OF SHUNT

flow ratio= PBF/SBF (or QP/QS)

<1.5 small left-to-right shunt.

≥2.0 large left-to-right shunt.

<1.0 right-to-left shunt.

If oxygen consumption is not measured:

INDICATOR DILUTION METHOD More sensitive than the oximetric method in detection of

small shunts.

Cannot be used to localize the level of a left-to-right shunt.

Dye used- Indocyanine Green.

Left to Right : Dye is injected into pulmonary artery and a sample is taken from the systemic artery.

Right to Left: dye injected just proximal to the presumed shunt and blood sample is taken from systemic artery

SHUNT ESTIMATION BY ECHOCARDIOGRAPHY

PW Doppler or color flow imaging:flow disturbance is found downstream from the

defect.velocity of blood flow through the shunt orifice

is related to the pressure gradient

2D imaging;ASD-Dilation RA and RV,paradoxical septal

motion .PDA & VSD: Dilation LA and LV.

IMPORTANCE OF PULMONARY VASCULAR RESISTANCE CONGENITAL CENTRAL SHUNTS

The decision as to whether a patient with congenital heart disease would profit from corrective surgery often hinges on the calculated pulmonary vascular resistance.

IMPORTANT CALCULATIONS: PVR PVR:SVR ratio.

PULMONARY VASCULAR RESISTANCE

PVR = mean PAP – mean LAP (or PCWP)Qp

-in Woods Unit (mmHg/L/min)

SVR = mean systemic arterial P – mean RAP

Qs

PVRI= PVR/ BSA (Sq. m.)

FAVOURABLE OUTCOME IN SURGERY

A baseline PVRI <6 Woods units/m2 associated with a resistance ratio of <0.3 without a vasoreactivity test is interpreted as indicative of a favorable outcome following operations resulting in a biventricular circulation.

FAVORABLE OUTCOME IN SURGERY

Acute vasodilator challenge using oxygen/ nitric oxide: Done if baseline PVRI is between 6 and 9

Wood units/m2 in the presence of a resistance ratio from around 0.3-0.5.

favorable outcome: A decrease of 20% in the PVRI. A decrease of around 20% in the ratio of

pulmonary to systemic vascular resistance A final PVR index of <6 Woods units/m2. A final ratio of resistance of <0.3.

THANK YOU……

Pulmonary hypertension with cardiac shunt determination

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