Pulmonary Pulmonary HypertensionHypertension

Pulmonary Pulmonary HypertensionHypertension

Allison K. Cabalka, MDAllison K. Cabalka, MDAssociate Professor of PediatricsAssociate Professor of PediatricsConsultant, Pediatric CardiologyConsultant, Pediatric Cardiology

Mayo ClinicMayo Clinic

Allison K. Cabalka, MDAllison K. Cabalka, MDAssociate Professor of PediatricsAssociate Professor of PediatricsConsultant, Pediatric CardiologyConsultant, Pediatric Cardiology

Mayo ClinicMayo Clinic

CHD and PHTN: IssuesCHD and PHTN: IssuesCHD and PHTN: IssuesCHD and PHTN: Issues

•What is Pulmonary HTN?What is Pulmonary HTN? How does one define elevated How does one define elevated

pulmonary artery pressurepulmonary artery pressure Classification schemeClassification scheme

•How do we assess PHTN in How do we assess PHTN in those with CHD?those with CHD? Non-invasive: clinical, echoNon-invasive: clinical, echo Invasive: cath evaluationInvasive: cath evaluation

•Treatment of PHTN?Treatment of PHTN?

•What is Pulmonary HTN?What is Pulmonary HTN? How does one define elevated How does one define elevated

pulmonary artery pressurepulmonary artery pressure Classification schemeClassification scheme

•How do we assess PHTN in How do we assess PHTN in those with CHD?those with CHD? Non-invasive: clinical, echoNon-invasive: clinical, echo Invasive: cath evaluationInvasive: cath evaluation

•Treatment of PHTN?Treatment of PHTN?

What is Pulmonary HTN?What is Pulmonary HTN?What is Pulmonary HTN?What is Pulmonary HTN?

•Simple DescriptionSimple DescriptionElevated PA pressureElevated PA pressure(( pulm vein pressure) pulm vein pressure)

•DefinitionDefinition (mm Hg)(mm Hg)PA pressurePA pressure >30/15>30/15PA (mean)PA (mean) >25>25

MildMild 26-3526-35ModerateModerate 36-5036-50SevereSevere >50>50

•Simple DescriptionSimple DescriptionElevated PA pressureElevated PA pressure(( pulm vein pressure) pulm vein pressure)

•DefinitionDefinition (mm Hg)(mm Hg)PA pressurePA pressure >30/15>30/15PA (mean)PA (mean) >25>25

MildMild 26-3526-35ModerateModerate 36-5036-50SevereSevere >50>50

Why is PTHN Important?Why is PTHN Important?Why is PTHN Important?Why is PTHN Important?

•It is a disease of the entire It is a disease of the entire pulmonary circulationpulmonary circulation

•It is a critical determinant of It is a critical determinant of outcomeoutcome Morbidity, mortality in pediatric lung, Morbidity, mortality in pediatric lung,

cardiac, pulmonary, hematologic, and cardiac, pulmonary, hematologic, and other diseasesother diseases

•It is a disease of the entire It is a disease of the entire pulmonary circulationpulmonary circulation

•It is a critical determinant of It is a critical determinant of outcomeoutcome Morbidity, mortality in pediatric lung, Morbidity, mortality in pediatric lung,

cardiac, pulmonary, hematologic, and cardiac, pulmonary, hematologic, and other diseasesother diseases

Evian-Venice ClassificationEvian-Venice ClassificationEvian-Venice ClassificationEvian-Venice Classification

•PHTN in the setting of CHD with PHTN in the setting of CHD with systemic to PA shuntssystemic to PA shunts Classified as Pulmonary Classified as Pulmonary ArterialArterial

HypertensionHypertension

•Considering the following:Considering the following: Type of CHDType of CHD Prognosis/evolution of pulmonary vascular Prognosis/evolution of pulmonary vascular

diseasedisease Circulatory physiologyCirculatory physiology

•PHTN in the setting of CHD with PHTN in the setting of CHD with systemic to PA shuntssystemic to PA shunts Classified as Pulmonary Classified as Pulmonary ArterialArterial

HypertensionHypertension

•Considering the following:Considering the following: Type of CHDType of CHD Prognosis/evolution of pulmonary vascular Prognosis/evolution of pulmonary vascular

diseasedisease Circulatory physiologyCirculatory physiology

World Symposiums on PHTN; Evian 1998 and Venice 2003

Characterizing PHTN in CHDCharacterizing PHTN in CHDCharacterizing PHTN in CHDCharacterizing PHTN in CHD

•Presence of systemic-to-Presence of systemic-to-pulmonary shuntpulmonary shunt Location of shuntLocation of shunt Direction of shuntDirection of shunt Size of defectSize of defect

•State of repairState of repair•Associated cardiac anomalies Associated cardiac anomalies

•Presence of systemic-to-Presence of systemic-to-pulmonary shuntpulmonary shunt Location of shuntLocation of shunt Direction of shuntDirection of shunt Size of defectSize of defect

•State of repairState of repair•Associated cardiac anomalies Associated cardiac anomalies

Evian/Venice Classification

Systemic-to-Pulmonary ShuntSystemic-to-Pulmonary ShuntSystemic-to-Pulmonary ShuntSystemic-to-Pulmonary Shunt

•Yes/NoYes/No•Previously present by history? Previously present by history?

If not, consider another classification If not, consider another classification system (such as WHO)system (such as WHO)

•For purposes of For purposes of thisthis discussion, discussion, we will assume all pts have a we will assume all pts have a shunt lesion (CHD)shunt lesion (CHD)

•Yes/NoYes/No•Previously present by history? Previously present by history?

If not, consider another classification If not, consider another classification system (such as WHO)system (such as WHO)

•For purposes of For purposes of thisthis discussion, discussion, we will assume all pts have a we will assume all pts have a shunt lesion (CHD)shunt lesion (CHD)

Evian/Venice Classification

Location of Shunt?Location of Shunt?Location of Shunt?Location of Shunt?

•Pre-tricuspid levelPre-tricuspid level Inter-atrial communication (ASD)Inter-atrial communication (ASD) Anomalous pulmonary venous Anomalous pulmonary venous

drainage/connectiondrainage/connection

•Post-tricuspid levelPost-tricuspid level Ventricular septal defect (VSD)Ventricular septal defect (VSD) Patent ductus arteriosus/AP windowPatent ductus arteriosus/AP window Functionally univentricular heartsFunctionally univentricular hearts

•Pre-tricuspid levelPre-tricuspid level Inter-atrial communication (ASD)Inter-atrial communication (ASD) Anomalous pulmonary venous Anomalous pulmonary venous

drainage/connectiondrainage/connection

•Post-tricuspid levelPost-tricuspid level Ventricular septal defect (VSD)Ventricular septal defect (VSD) Patent ductus arteriosus/AP windowPatent ductus arteriosus/AP window Functionally univentricular heartsFunctionally univentricular hearts

Evian/Venice Classification

Where is the Shunt?Where is the Shunt?Where is the Shunt?Where is the Shunt?

Direction of Shunt?Direction of Shunt?Direction of Shunt?Direction of Shunt?

•Systemic to pulmonarySystemic to pulmonary Left-to-rightLeft-to-right

•Pulmonary to systemicPulmonary to systemic Right-to-leftRight-to-left

•BidirectionalBidirectional

•Systemic to pulmonarySystemic to pulmonary Left-to-rightLeft-to-right

•Pulmonary to systemicPulmonary to systemic Right-to-leftRight-to-left

•BidirectionalBidirectional

Evian/Venice Classification

Size of Defect?Size of Defect?Size of Defect?Size of Defect?

•Anatomic and functionalAnatomic and functional•Consider size at presentation Consider size at presentation

and current sizeand current size•Quantification of shuntQuantification of shunt

Ratio of pulmonary and systemic Ratio of pulmonary and systemic flowsflows

•Restriction? Restriction? Is there any pressure gradient Is there any pressure gradient

through the post-tricuspid defect?through the post-tricuspid defect?

•Anatomic and functionalAnatomic and functional•Consider size at presentation Consider size at presentation

and current sizeand current size•Quantification of shuntQuantification of shunt

Ratio of pulmonary and systemic Ratio of pulmonary and systemic flowsflows

•Restriction? Restriction? Is there any pressure gradient Is there any pressure gradient

through the post-tricuspid defect?through the post-tricuspid defect?Evian/Venice Classification

State of Repair?State of Repair?State of Repair?State of Repair?

•UnoperatedUnoperated•PalliatedPalliated

Age at repairAge at repair Type of surgeryType of surgery

•RepairedRepaired Age at repairAge at repair Type of surgeryType of surgery

•UnoperatedUnoperated•PalliatedPalliated

Age at repairAge at repair Type of surgeryType of surgery

•RepairedRepaired Age at repairAge at repair Type of surgeryType of surgery

Modified from Venice 2003

IF Postoperative Patient?IF Postoperative Patient?IF Postoperative Patient?IF Postoperative Patient?

•Correction of shunt and age at Correction of shunt and age at correctioncorrection•Pulmonary arterial bandingPulmonary arterial banding

Age at PAB, duration of bandingAge at PAB, duration of banding

•Presence and type of surgical Presence and type of surgical shuntsshunts Blalock-Taussig, Pott’s, WaterstonBlalock-Taussig, Pott’s, Waterston

•Residual shuntingResidual shunting Quantification and directionQuantification and direction

•Correction of shunt and age at Correction of shunt and age at correctioncorrection•Pulmonary arterial bandingPulmonary arterial banding

Age at PAB, duration of bandingAge at PAB, duration of banding

•Presence and type of surgical Presence and type of surgical shuntsshunts Blalock-Taussig, Pott’s, WaterstonBlalock-Taussig, Pott’s, Waterston

•Residual shuntingResidual shunting Quantification and directionQuantification and direction

Evian/Venice Classification

Associated Cardiac AnomaliesAssociated Cardiac AnomaliesAssociated Cardiac AnomaliesAssociated Cardiac Anomalies

Especially those that affect Especially those that affect pulmonary hemodynamics:pulmonary hemodynamics:

•Pulmonary valve stenosisPulmonary valve stenosis•Defects affecting pulmonary Defects affecting pulmonary

venous “outflow”venous “outflow” Cor triatriatum, mitral stenosis, LV Cor triatriatum, mitral stenosis, LV

dysfunctiondysfunction•Ventricular functionVentricular function

Systolic, diastolic Systolic, diastolic Overall cardiac outputOverall cardiac output

Especially those that affect Especially those that affect pulmonary hemodynamics:pulmonary hemodynamics:

•Pulmonary valve stenosisPulmonary valve stenosis•Defects affecting pulmonary Defects affecting pulmonary

venous “outflow”venous “outflow” Cor triatriatum, mitral stenosis, LV Cor triatriatum, mitral stenosis, LV

dysfunctiondysfunction•Ventricular functionVentricular function

Systolic, diastolic Systolic, diastolic Overall cardiac outputOverall cardiac output

Evian/Venice Classification

Considering CHD and PHTNConsidering CHD and PHTNConsidering CHD and PHTNConsidering CHD and PHTN

Basic issues at presentation:Basic issues at presentation:• Is the patient still repairable?Is the patient still repairable?

Is the shunt lesion recognized in a Is the shunt lesion recognized in a timely fashion?timely fashion?

• Is the pulmonary hypertension Is the pulmonary hypertension reversible?reversible?

There may be a point of “no return” There may be a point of “no return” but the time course varies widely but the time course varies widely from patient to patient…from patient to patient…

Basic issues at presentation:Basic issues at presentation:• Is the patient still repairable?Is the patient still repairable?

Is the shunt lesion recognized in a Is the shunt lesion recognized in a timely fashion?timely fashion?

• Is the pulmonary hypertension Is the pulmonary hypertension reversible?reversible?

There may be a point of “no return” There may be a point of “no return” but the time course varies widely but the time course varies widely from patient to patient…from patient to patient…

Pulmonary Arterial HTNPulmonary Arterial HTNPulmonary Arterial HTNPulmonary Arterial HTN

In patients with CHD:In patients with CHD:•Pulmonary artery is exposed to Pulmonary artery is exposed to

systemic pressure when VSD or systemic pressure when VSD or PDA is unrestrictivePDA is unrestrictive•Pulmonary HTNPulmonary HTN is present from is present from

birthbirth•Pulmonary vascular resistancePulmonary vascular resistance

determines outcomedetermines outcome

In patients with CHD:In patients with CHD:•Pulmonary artery is exposed to Pulmonary artery is exposed to

systemic pressure when VSD or systemic pressure when VSD or PDA is unrestrictivePDA is unrestrictive•Pulmonary HTNPulmonary HTN is present from is present from

birthbirth•Pulmonary vascular resistancePulmonary vascular resistance

determines outcomedetermines outcome

What What isis the Point of No Return? the Point of No Return?What What isis the Point of No Return? the Point of No Return?

Eisenmenger Eisenmenger syndrome:syndrome:

•Pulmonary Pulmonary vascular vascular resistance is resistance is elevatedelevated

•Shunt reverses Shunt reverses and becomes and becomes right-to-leftright-to-left

Eisenmenger Eisenmenger syndrome:syndrome:

•Pulmonary Pulmonary vascular vascular resistance is resistance is elevatedelevated

•Shunt reverses Shunt reverses and becomes and becomes right-to-leftright-to-left

PVD: Who is at Risk?PVD: Who is at Risk?PVD: Who is at Risk?PVD: Who is at Risk?

Pulmonary Pulmonary VascularVascularDiseaseDisease

Pulmonary Pulmonary VascularVascularDiseaseDisease

Shunt + Shunt + Pulmonary Pulmonary

HypertensionHypertension

Shunt + Shunt + Pulmonary Pulmonary

HypertensionHypertension

Particularly if there is CyanosisParticularly if there is Cyanosis

Two Ventricles…Two Ventricles…Two Ventricles…Two Ventricles…

•Large VSD, Large PDALarge VSD, Large PDA•Combined intracardiac shunts Combined intracardiac shunts

i.e. d-TGA with VSD; DORVi.e. d-TGA with VSD; DORV Cyanosis and mixing is a BAD combinationCyanosis and mixing is a BAD combination

•What about large ASD?What about large ASD? This may be a separate issue This may be a separate issue

i.e. Primary pulmonary HTNi.e. Primary pulmonary HTN

•Other factors:Other factors: Pulmonary venous obstruction, arch Pulmonary venous obstruction, arch

obstruction (Shone’s syndrome), AV valve obstruction (Shone’s syndrome), AV valve regurgitationregurgitation

•Large VSD, Large PDALarge VSD, Large PDA•Combined intracardiac shunts Combined intracardiac shunts

i.e. d-TGA with VSD; DORVi.e. d-TGA with VSD; DORV Cyanosis and mixing is a BAD combinationCyanosis and mixing is a BAD combination

•What about large ASD?What about large ASD? This may be a separate issue This may be a separate issue

i.e. Primary pulmonary HTNi.e. Primary pulmonary HTN

•Other factors:Other factors: Pulmonary venous obstruction, arch Pulmonary venous obstruction, arch

obstruction (Shone’s syndrome), AV valve obstruction (Shone’s syndrome), AV valve regurgitationregurgitation

One Ventricle…One Ventricle…One Ventricle…One Ventricle…

•Basically anyone with an Basically anyone with an unprotectedunprotected PA bed (no PS) PA bed (no PS) Tricuspid atresia with unrestrictive Tricuspid atresia with unrestrictive

VSD, no PSVSD, no PS DILV without pulmonary stenosisDILV without pulmonary stenosis DORV with small LV, no PSDORV with small LV, no PS Ductal-dependent, complex CHD with Ductal-dependent, complex CHD with

persistently large PDApersistently large PDA

•Basically anyone with an Basically anyone with an unprotectedunprotected PA bed (no PS) PA bed (no PS) Tricuspid atresia with unrestrictive Tricuspid atresia with unrestrictive

VSD, no PSVSD, no PS DILV without pulmonary stenosisDILV without pulmonary stenosis DORV with small LV, no PSDORV with small LV, no PS Ductal-dependent, complex CHD with Ductal-dependent, complex CHD with

persistently large PDApersistently large PDA

Assessment of PHTNAssessment of PHTNAssessment of PHTNAssessment of PHTNIn the Setting of CHDIn the Setting of CHDIn the Setting of CHDIn the Setting of CHD

Assessment in CHDAssessment in CHDAssessment in CHDAssessment in CHD

•Early recognition and referral of Early recognition and referral of CHD is criticalCHD is critical This is extremely important! This is extremely important! Natural history may vary; timing or Natural history may vary; timing or

presentation may also varypresentation may also vary

•Clinical evaluationClinical evaluation Symptoms, growth pattern, other Symptoms, growth pattern, other

illnesses and hospitalizations?illnesses and hospitalizations? Physical examinationPhysical examination Laboratory evaluationLaboratory evaluation

•Early recognition and referral of Early recognition and referral of CHD is criticalCHD is critical This is extremely important! This is extremely important! Natural history may vary; timing or Natural history may vary; timing or

presentation may also varypresentation may also vary

•Clinical evaluationClinical evaluation Symptoms, growth pattern, other Symptoms, growth pattern, other

illnesses and hospitalizations?illnesses and hospitalizations? Physical examinationPhysical examination Laboratory evaluationLaboratory evaluation

Clinical Assessment in CHDClinical Assessment in CHDClinical Assessment in CHDClinical Assessment in CHD

Clinical exam: Clinical exam: •Does the patient have evidence of Does the patient have evidence of

large L-to-R shunt?large L-to-R shunt? S2, P2 componentS2, P2 component Continuous PDA murmurContinuous PDA murmur Systolic murmur with diastolic flow rumble Systolic murmur with diastolic flow rumble

through mitral valvethrough mitral valve•Or not?Or not?

Loud, single S2 (P2), minimal murmurLoud, single S2 (P2), minimal murmur Very short systolic murmurVery short systolic murmur No flow rumble or continuous murmurNo flow rumble or continuous murmur

Clinical exam: Clinical exam: •Does the patient have evidence of Does the patient have evidence of

large L-to-R shunt?large L-to-R shunt? S2, P2 componentS2, P2 component Continuous PDA murmurContinuous PDA murmur Systolic murmur with diastolic flow rumble Systolic murmur with diastolic flow rumble

through mitral valvethrough mitral valve•Or not?Or not?

Loud, single S2 (P2), minimal murmurLoud, single S2 (P2), minimal murmur Very short systolic murmurVery short systolic murmur No flow rumble or continuous murmurNo flow rumble or continuous murmur

Is the patient PINK or cyanotic?

CXR in Shunt PhysiologyCXR in Shunt PhysiologyCXR in Shunt PhysiologyCXR in Shunt Physiology

This should be reassuring…This should be reassuring…

CXR in Shunt PhysiologyCXR in Shunt PhysiologyCXR in Shunt PhysiologyCXR in Shunt Physiology

This is more reassuring…This is more reassuring…

CXR in Shunt PhysiologyCXR in Shunt PhysiologyCXR in Shunt PhysiologyCXR in Shunt Physiology

This is NOT reassuring…This is NOT reassuring…

Echo AssessmentEcho AssessmentEcho AssessmentEcho Assessment

Careful evaluation of anatomy Careful evaluation of anatomy and physiology:and physiology:•Confirmation of location, size Confirmation of location, size

and associated defectsand associated defects Doppler profile (velocity)Doppler profile (velocity) Shunt direction, left-to-right; Shunt direction, left-to-right;

bidirectional; right-to-leftbidirectional; right-to-left Left-sided structural enlargementLeft-sided structural enlargement Associated valve pathologyAssociated valve pathology Ventricular functionVentricular function

Careful evaluation of anatomy Careful evaluation of anatomy and physiology:and physiology:•Confirmation of location, size Confirmation of location, size

and associated defectsand associated defects Doppler profile (velocity)Doppler profile (velocity) Shunt direction, left-to-right; Shunt direction, left-to-right;

bidirectional; right-to-leftbidirectional; right-to-left Left-sided structural enlargementLeft-sided structural enlargement Associated valve pathologyAssociated valve pathology Ventricular functionVentricular function

Echo AssessmentEcho AssessmentEcho AssessmentEcho Assessment

•Need to be very careful in the patient Need to be very careful in the patient with a large post-tricuspid defect (i.e. with a large post-tricuspid defect (i.e. VSD) to VSD) to NOTNOT miss other defects miss other defects Always evaluate the aortic arch and ductus very Always evaluate the aortic arch and ductus very

carefullycarefully Sometimes the PDA with bidirectional shunt is Sometimes the PDA with bidirectional shunt is

very easy to “miss”very easy to “miss”

•Be careful in the patient with Be careful in the patient with bidirectional or right-to-left shuntbidirectional or right-to-left shunt Suspicions of elevated pulmonary resistance?Suspicions of elevated pulmonary resistance? The patient needs hemodynamic cath studyThe patient needs hemodynamic cath study

•Need to be very careful in the patient Need to be very careful in the patient with a large post-tricuspid defect (i.e. with a large post-tricuspid defect (i.e. VSD) to VSD) to NOTNOT miss other defects miss other defects Always evaluate the aortic arch and ductus very Always evaluate the aortic arch and ductus very

carefullycarefully Sometimes the PDA with bidirectional shunt is Sometimes the PDA with bidirectional shunt is

very easy to “miss”very easy to “miss”

•Be careful in the patient with Be careful in the patient with bidirectional or right-to-left shuntbidirectional or right-to-left shunt Suspicions of elevated pulmonary resistance?Suspicions of elevated pulmonary resistance? The patient needs hemodynamic cath studyThe patient needs hemodynamic cath study

Shunts and ResistanceShunts and ResistanceShunts and ResistanceShunts and Resistance

•Resistance determination is the Resistance determination is the MAIN reason to cath a child/adult MAIN reason to cath a child/adult with CHDwith CHD•Meticulous collection of data!Meticulous collection of data!•Resistance is related to pressure Resistance is related to pressure

divided by flow:divided by flow:

•Resistance determination is the Resistance determination is the MAIN reason to cath a child/adult MAIN reason to cath a child/adult with CHDwith CHD•Meticulous collection of data!Meticulous collection of data!•Resistance is related to pressure Resistance is related to pressure

divided by flow:divided by flow:

RpaRpa = = Pressure drop across PA bed Pressure drop across PA bed

Flow Flow

Looking at Resistance Looking at Resistance Another WayAnother Way

Looking at Resistance Looking at Resistance Another WayAnother Way

•Relationship of pressure to flow Relationship of pressure to flow and resistanceand resistance

PAP = Flow (Qp) PAP = Flow (Qp) •• Resistance Resistance

•IMPT point: Increased pressure IMPT point: Increased pressure can have can have eithereither or or bothboth as as possible sourcespossible sources

•Relationship of pressure to flow Relationship of pressure to flow and resistanceand resistance

PAP = Flow (Qp) PAP = Flow (Qp) •• Resistance Resistance

•IMPT point: Increased pressure IMPT point: Increased pressure can have can have eithereither or or bothboth as as possible sourcespossible sources

The “Basic” Cath StudyThe “Basic” Cath StudyThe “Basic” Cath StudyThe “Basic” Cath Study

•Hemodynamics needed:Hemodynamics needed: RA and LA (PCWP), MPA mean, and RA and LA (PCWP), MPA mean, and

systemic artery mean pressuressystemic artery mean pressures

•Blood samples needed:Blood samples needed: Mixed venous (SVC), pulmonary Mixed venous (SVC), pulmonary

artery, pulmonary vein, aortaartery, pulmonary vein, aorta

•Typically done first in room airTypically done first in room air Calculate the Qp, Qs and Resistance Calculate the Qp, Qs and Resistance

•Perform 100% O2 studyPerform 100% O2 study

•Hemodynamics needed:Hemodynamics needed: RA and LA (PCWP), MPA mean, and RA and LA (PCWP), MPA mean, and

systemic artery mean pressuressystemic artery mean pressures

•Blood samples needed:Blood samples needed: Mixed venous (SVC), pulmonary Mixed venous (SVC), pulmonary

artery, pulmonary vein, aortaartery, pulmonary vein, aorta

•Typically done first in room airTypically done first in room air Calculate the Qp, Qs and Resistance Calculate the Qp, Qs and Resistance

•Perform 100% O2 studyPerform 100% O2 study

Cath: Basic FormulasCath: Basic FormulasCath: Basic FormulasCath: Basic Formulas

•Shunts from O2 saturation dataShunts from O2 saturation dataQp = Pulmonary blood flow (index)

Qp = VO2 / (PV sat-PA sat) (O2 capacity)

Qs = Systemic blood flow (index)

Qs = VO2 / (SA sat- MV sat) (O2 capacity)

VO2 = Oxygen consumption (ml/min/m2)VO2 = Oxygen consumption (ml/min/m2) O2 Capacity = 13.6 x Hgb (gm/dL)O2 Capacity = 13.6 x Hgb (gm/dL)

•Shunts from O2 saturation dataShunts from O2 saturation dataQp = Pulmonary blood flow (index)

Qp = VO2 / (PV sat-PA sat) (O2 capacity)

Qs = Systemic blood flow (index)

Qs = VO2 / (SA sat- MV sat) (O2 capacity)

VO2 = Oxygen consumption (ml/min/m2)VO2 = Oxygen consumption (ml/min/m2) O2 Capacity = 13.6 x Hgb (gm/dL)O2 Capacity = 13.6 x Hgb (gm/dL)

Dissolved Oxygen ?Dissolved Oxygen ?Dissolved Oxygen ?Dissolved Oxygen ?

•O2 content = O2 capacity x O2 O2 content = O2 capacity x O2 saturation + PaO2 x .03ml/mmHgsaturation + PaO2 x .03ml/mmHg Hgb 11.5 gm/dlHgb 11.5 gm/dl Room air; PV pO2 = 106Room air; PV pO2 = 106

Oxygen content =(11.5x13.6x0.99)+ Oxygen content =(11.5x13.6x0.99)+ (106x0.03) = 155 + 3.3 = 158(106x0.03) = 155 + 3.3 = 158

100% Oxygen; PV pO2 = 566, sat 100%100% Oxygen; PV pO2 = 566, sat 100%Oxygen content = (11.5x13.6x1.0) + Oxygen content = (11.5x13.6x1.0) +

(566x0.03) = 156 + 17 = 173(566x0.03) = 156 + 17 = 173

•O2 content = O2 capacity x O2 O2 content = O2 capacity x O2 saturation + PaO2 x .03ml/mmHgsaturation + PaO2 x .03ml/mmHg Hgb 11.5 gm/dlHgb 11.5 gm/dl Room air; PV pO2 = 106Room air; PV pO2 = 106

Oxygen content =(11.5x13.6x0.99)+ Oxygen content =(11.5x13.6x0.99)+ (106x0.03) = 155 + 3.3 = 158(106x0.03) = 155 + 3.3 = 158

100% Oxygen; PV pO2 = 566, sat 100%100% Oxygen; PV pO2 = 566, sat 100%Oxygen content = (11.5x13.6x1.0) + Oxygen content = (11.5x13.6x1.0) +

(566x0.03) = 156 + 17 = 173(566x0.03) = 156 + 17 = 173

Dissolved Oxygen?Dissolved Oxygen?Dissolved Oxygen?Dissolved Oxygen?

•Remember that Qp = Remember that Qp = VO2 / VO2 / (PV sat-PA sat) x (O(PV sat-PA sat) x (O22 capacity) capacity)

•If we ignore dissolved O2 then we If we ignore dissolved O2 then we have a smaller number in have a smaller number in denominator, and a “higher” Qpdenominator, and a “higher” Qp

•This will This will falselyfalsely reduce the Rpa in reduce the Rpa in calculations…calculations…

•Remember that Qp = Remember that Qp = VO2 / VO2 / (PV sat-PA sat) x (O(PV sat-PA sat) x (O22 capacity) capacity)

•If we ignore dissolved O2 then we If we ignore dissolved O2 then we have a smaller number in have a smaller number in denominator, and a “higher” Qpdenominator, and a “higher” Qp

•This will This will falselyfalsely reduce the Rpa in reduce the Rpa in calculations…calculations…

* Resistance = PAP/ Flow (Qp) * Resistance = PAP/ Flow (Qp)

Rpa: Pulmonary ResistanceRpa: Pulmonary ResistanceRpa: Pulmonary ResistanceRpa: Pulmonary Resistance

•Normal Normal ≤≤ 3 wood units 3 wood units••mm22

•Borderline between 3-6 wood Borderline between 3-6 wood unitsunits••mm22

•Over 6 wood unitsOver 6 wood units••mm22

QuestionableQuestionable PHTN may persist or progressPHTN may persist or progress May treat for reversibility over timeMay treat for reversibility over time

•Eisenmenger physiology pts Eisenmenger physiology pts usually live longer than those usually live longer than those with repair!with repair!

•Normal Normal ≤≤ 3 wood units 3 wood units••mm22

•Borderline between 3-6 wood Borderline between 3-6 wood unitsunits••mm22

•Over 6 wood unitsOver 6 wood units••mm22

QuestionableQuestionable PHTN may persist or progressPHTN may persist or progress May treat for reversibility over timeMay treat for reversibility over time

•Eisenmenger physiology pts Eisenmenger physiology pts usually live longer than those usually live longer than those with repair!with repair!

What about Altitude?What about Altitude?What about Altitude?What about Altitude?

Altitude PhysiologyAltitude PhysiologyAltitude PhysiologyAltitude Physiology

•Potential contribution of altitudePotential contribution of altitude Delayed transition of decline in Delayed transition of decline in

pulmonary vascular resistancepulmonary vascular resistanceDelayed remodeling of vascular Delayed remodeling of vascular

bedbedIncreased muscularization of Increased muscularization of

arteriesarteries Persistence of the PDAPersistence of the PDA

•High altitudeHigh altitude Living above 4000 metersLiving above 4000 meters These changes are even more These changes are even more

accentuatedaccentuated

•Potential contribution of altitudePotential contribution of altitude Delayed transition of decline in Delayed transition of decline in

pulmonary vascular resistancepulmonary vascular resistanceDelayed remodeling of vascular Delayed remodeling of vascular

bedbedIncreased muscularization of Increased muscularization of

arteriesarteries Persistence of the PDAPersistence of the PDA

•High altitudeHigh altitude Living above 4000 metersLiving above 4000 meters These changes are even more These changes are even more

accentuatedaccentuated

Treatment Options?Treatment Options?Treatment Options?Treatment Options?

Treatment of Elevated RpaTreatment of Elevated RpaTreatment of Elevated RpaTreatment of Elevated Rpa

Once you’ve demonstrated that Once you’ve demonstrated that Rpa is elevated…Rpa is elevated…•Treatment with pulmonary Treatment with pulmonary

vasodilator therapyvasodilator therapy Sildenafil Sildenafil BosentanBosentan Other more complex regimens are not Other more complex regimens are not

usually practicalusually practical

Once you’ve demonstrated that Once you’ve demonstrated that Rpa is elevated…Rpa is elevated…•Treatment with pulmonary Treatment with pulmonary

vasodilator therapyvasodilator therapy Sildenafil Sildenafil BosentanBosentan Other more complex regimens are not Other more complex regimens are not

usually practicalusually practical

SildenafilSildenafilSildenafilSildenafil

•Cyclic GMP Phosphodiesterase Cyclic GMP Phosphodiesterase type 5 inhibitortype 5 inhibitor Prolongs vasodilatory effect of nitric Prolongs vasodilatory effect of nitric

oxideoxide

•Cyclic GMP Phosphodiesterase Cyclic GMP Phosphodiesterase type 5 inhibitortype 5 inhibitor Prolongs vasodilatory effect of nitric Prolongs vasodilatory effect of nitric

oxideoxide

SildenafilSildenafilSildenafilSildenafil

•Typical adult dose = 20 mg TIDTypical adult dose = 20 mg TID•Pediatric dosing Pediatric dosing

Initial dose: 0.5 mg/kg/dose every 8 Initial dose: 0.5 mg/kg/dose every 8 hours hours

Increased if needed and if tolerated Increased if needed and if tolerated Typical maximum: 2 mg/kg/dose Typical maximum: 2 mg/kg/dose

every 6-8 hours every 6-8 hours

•Typical adult dose = 20 mg TIDTypical adult dose = 20 mg TID•Pediatric dosing Pediatric dosing

Initial dose: 0.5 mg/kg/dose every 8 Initial dose: 0.5 mg/kg/dose every 8 hours hours

Increased if needed and if tolerated Increased if needed and if tolerated Typical maximum: 2 mg/kg/dose Typical maximum: 2 mg/kg/dose

every 6-8 hours every 6-8 hours

BosentanBosentanBosentanBosentan

•Endothelin receptor antagonistEndothelin receptor antagonist Endothelin-1 receptors are potent Endothelin-1 receptors are potent

vasoconstrictors; found in higher vasoconstrictors; found in higher concentration in lungs of PTHN ptsconcentration in lungs of PTHN pts

•BREATHE – 5BREATHE – 5 Reduced RpaReduced Rpa Improved 6 min walk distanceImproved 6 min walk distance With Rx effects may be maintained for 2 With Rx effects may be maintained for 2

yrs (may improve PHTN mortality)yrs (may improve PHTN mortality)

•Endothelin receptor antagonistEndothelin receptor antagonist Endothelin-1 receptors are potent Endothelin-1 receptors are potent

vasoconstrictors; found in higher vasoconstrictors; found in higher concentration in lungs of PTHN ptsconcentration in lungs of PTHN pts

•BREATHE – 5BREATHE – 5 Reduced RpaReduced Rpa Improved 6 min walk distanceImproved 6 min walk distance With Rx effects may be maintained for 2 With Rx effects may be maintained for 2

yrs (may improve PHTN mortality)yrs (may improve PHTN mortality)

BosentanBosentanBosentanBosentan

•DosageDosage 10-20 kg:10-20 kg: Initial: 31.25 mg daily for 4 Initial: 31.25 mg daily for 4

weeks; increase to maintenance dose of weeks; increase to maintenance dose of 31.25 mg twice daily31.25 mg twice daily

>20-40 kg:>20-40 kg: Initial: 31.25 mg twice daily for Initial: 31.25 mg twice daily for 4 weeks; increase to maintenance dose of 4 weeks; increase to maintenance dose of 62.5 mg twice daily62.5 mg twice daily

>40 kg:>40 kg: Initial: 62.5 mg twice daily for 4 Initial: 62.5 mg twice daily for 4 weeks; increase to maintenance dose of weeks; increase to maintenance dose of 125 mg twice daily125 mg twice daily

•Must monitor liver enzymesMust monitor liver enzymes

•DosageDosage 10-20 kg:10-20 kg: Initial: 31.25 mg daily for 4 Initial: 31.25 mg daily for 4

weeks; increase to maintenance dose of weeks; increase to maintenance dose of 31.25 mg twice daily31.25 mg twice daily

>20-40 kg:>20-40 kg: Initial: 31.25 mg twice daily for Initial: 31.25 mg twice daily for 4 weeks; increase to maintenance dose of 4 weeks; increase to maintenance dose of 62.5 mg twice daily62.5 mg twice daily

>40 kg:>40 kg: Initial: 62.5 mg twice daily for 4 Initial: 62.5 mg twice daily for 4 weeks; increase to maintenance dose of weeks; increase to maintenance dose of 125 mg twice daily125 mg twice daily

•Must monitor liver enzymesMust monitor liver enzymes

Take Home PointsTake Home PointsTake Home PointsTake Home Points

•Patient with shunt lesion and Patient with shunt lesion and obvious increased PBF on obvious increased PBF on clinical/echo evaluation clinical/echo evaluation shouldshould be be repairablerepairable•Elevated Rpa on clinical Elevated Rpa on clinical

evaluation warrants further studyevaluation warrants further study Cardiac cath and OCardiac cath and O22 study study Evaluate shunt and reactivity of the Evaluate shunt and reactivity of the

pulmonary vascular bedpulmonary vascular bed

•Patient with shunt lesion and Patient with shunt lesion and obvious increased PBF on obvious increased PBF on clinical/echo evaluation clinical/echo evaluation shouldshould be be repairablerepairable•Elevated Rpa on clinical Elevated Rpa on clinical

evaluation warrants further studyevaluation warrants further study Cardiac cath and OCardiac cath and O22 study study Evaluate shunt and reactivity of the Evaluate shunt and reactivity of the

pulmonary vascular bedpulmonary vascular bed

Take Home PointsTake Home PointsTake Home PointsTake Home Points

•Early recognition is criticalEarly recognition is critical If evidence of increased pulmonary If evidence of increased pulmonary

resistance consider treatment with resistance consider treatment with pulmonary vasodilator therapypulmonary vasodilator therapy

•In patients with obvious In patients with obvious Eisenmenger physiology it is Eisenmenger physiology it is better to leave them alonebetter to leave them alone They will survive longer!!!They will survive longer!!!

•Early recognition is criticalEarly recognition is critical If evidence of increased pulmonary If evidence of increased pulmonary

resistance consider treatment with resistance consider treatment with pulmonary vasodilator therapypulmonary vasodilator therapy

•In patients with obvious In patients with obvious Eisenmenger physiology it is Eisenmenger physiology it is better to leave them alonebetter to leave them alone They will survive longer!!!They will survive longer!!!