PULMONARY ARTERIAL HYPERTENSION IN CHD

Dr. K.V.Siva Krishna

Emryology

Normal pulmonary circulation• High flow, low pressure and low resistance circulation• Unique double arterial blood supply• Pulmonary arteries:

– Elastic: conducting vessel, ≥ 500 μm, highly distensible– Muscular: 100-500 μm, no elastin, non distensible– Arterioles: ≤ 100 μm, thin intima and single elastic lamina

• Bronchial arteries: nutrition to the airways

Development of Pulmonary circulation

• It was observed from the postmortem arteriograms that the vessels are prominent in the newborn, whereas in the adult they are obscured by a dense background haze produced by the addition of many small intra-acinar arteries not present at birth.

• Foetus : With increasing age, muscle is observed in arteries located more peripherally within the acinus.

• At first nonmuscular arteries become partially muscular, and later they become fully muscularized.

• At birth: The muscularized arteries are thick walled, but within a few days, the smallest muscular arteries dilate, and their walls thin to adult levels.

• @4 months of age: This process has included the largest muscular pulmonary arteries and is complete.

• Arteries grow both in number and size, and they grow most rapidly in infancy.

• The latter process contributes >90% of the smaller or intra-acinar pulmonary arterial vessels present in the older child and adult

• Development of new arteries and arterioles occur.

• Although alveoli also proliferate, the ratio of alveoli to arteries actually decreases from the newborn value of 20:1 to the value of 8:1, which is achieved first in early childhood and persists.

CHANGES AFTER BIRTH• At birth PBF increases 8-10 times with a fall in

pulmonary pressure to a level less than 50% of systemic pressure

• Pulmonary vascular resistance may be as high as 8 to 10 Wood units immediately after birth, it normally falls rapidly throughout the first week of life.

• By 6 to 8 weeks, pulmonary vascular resistance usually has reached a normal adult level of 1 to 3 Wood units

• PH is defined as a mean pulmonary artery pressure >25 mm Hg at rest or >30 mm Hg during exercise.

• The term PAH describes a group of PH patients characterized haemodynamically by the presence of pre-capillary PH, defined by a pulmonary artery wedge pressure (PAWP) ≤15 mmHg and a PVRI >3 Wood units*m2 (WU).

Definition

• In Single Ventricle physiology • PAH is defined as • PVRI > 3WU• Trans pulmonary gradient (TPG) > 6mmhg

PATHOPHYSIOLOGY of PAH • Panvasculopathy predominantly affecting small PA• Exact mechanism is unknown, abnormalities in pulmonary

artery endothelial & smooth muscle cells (PASMCs) with varying degrees of

I. Vasoconstriction, [PASMCs, K+ &Ca2+ channels]

II. Vascular proliferation, [PASMCs, ECM syn.] SERT ON PASMCs: apoptosis, proliferation

III. Thrombosis, and IV. Inflammationcontribute to the development of pulmonary

hypertension

Pathophysiology of PAH

PAH in children• Causes • Pulmonary vascular obstructive disease related

to congenital heart disease (i.e., Eisenmenger syndrome) develops after a period of decreased pulmonary vascular resistance and increased pulmonary flow.

• In some children who have anatomically large systemic-to-pulmonary shunts (e.g., ventricular septal defect or patent ductus arteriosus), the pulmonary vascular obstructive disease occurs without there having been a large left-to-right shunt or signs of congestive heart failure, suggesting that the PAH may be idiopathic PAH rather than PAH related to the congenital heart disease.

• In pulmonary hypertension of the newborn (PPHN), there may be a failure of the normal decline in PVR after birth, which may be triggered by many factors related to neonatal stress

Eisenmenger Syndrome

Definition:Pulmonary hypertension at or near systemic level with reversed or bidirectional shunt between the pulmonary and systemic circulation at aorto-pulmonary, ventricular or atrial level and pulmonary vascular resistance above 800 dyne/cm-5 (10 Wood Units)

Paul Wood, Br Med J, 1958

Hemodynamically,• Eisenmenger syndrome (ES) is defined as

an elevation of the pulmonary vascular resistance to 12 Wood Units or to a pulmonary-to-systemic resistance ratio equal to or greater than 1.0

Eisenmenger Syndrome – A progressive disease

MECHANISM• Multifactorial

– Vasoconstriction– Proliferative and obstructive remodelling of the

pulmonary vascular bed– Inflammation and thrombosis– Failure of endothelial cell apoptosis, intimal

proliferation, and irreversible PAH

• Stage I - Medial hypertrophy (reversible)• Stage II - Cellular Intimal hyperplasia in a abnormally

muscular artery (reversible)• Stage III - Lumen occlusion from intimal hyperplasia

of fibroelastic tissue (partially reversible)• Stage IV - Arteriolar dilation and medial thinning

(irreversible)• Stage V - Plexiform lesion, which is an angiomatoid

formation (terminal and irreversible)• Stage VI - Fibrinoid/necrotizing arteritis (terminal and

irreversible

Heath-Edwards Classification – pathology of PAH

Reversible

Irreversible

Lung biospy

Grade Peripheral arteries Medial thickness(muscular arteries)

Arterial concerntration

Grade A Muscle extened into peripheral arteries

<1.5 times N

Normal Grade B ( mild ) Increased extension

1.5 to 2 times

Grade B (severe) > 2 times N

Grade C Arterial concerntration and size reduced

• A biopsy showing severe grade C and grade III or greater changes in 20% of vessels indicative of severe vascular disease that is unlikely to regress postoperatively.

• Severe grade B, or grade II changes in any vessel may preclude a favorable result from a Fontan procedure.

PRESSURE = FLOW X RESISTANCE

HYPERKINETIC PAH OBSTRUCTIVE PAH

• Age of the patient and complexity of lesion influence development of ES.

• Significant biologic variability exists in the clinical presentation and prognosis of underlying CHD

• BMPR2 mutations in patients with PAH in CHD. • These data raise the possibility that the presence of

a genetic predisposition in some patients with CHD may contribute to the observed biologic variability

• Pathologically similar to primary PAH• Endothelial proliferation is polyclonal in ES while

monoclonal in IPAH• Certain vascular patterns are different between

the two-– Persistent foetal pattern in large PA with elastic fibres

being long and densely packed as in the aorta – persistence of the foetal type of muscular artery

• Better appreciated with VSD & PDA than ASD

LESS WITH ES THAN IPAH

Vascular abnormalities associated with pulmonary hypertension

NATURAL HISTORY• Survival, as measured by age reached • 30 years of age: 75%• 40 years of age: 70%• 55 years of age: 55%

• IPAH –NIH registry -1,3,5 yr survival -68%,48%,38%

Diller, et al..Model of chronic adaptation: right ventricular function in Eisenmenger syndrome European Heart Journal Supplements 9

• Transplant free survival --• 97% at 1 year, 89% at 2 years, and 77% at

3 years for patients with ES • 77%, 69%, and 35%, respectively, for

patients with PPH

• Have a long symptom free time period• Patients have adjusted to a lower exercise capacity since

childhood. • Patients may even do well throughout adolescence and

early adulthood. • Many become symptomatic during their 30s and gradually

develop complaints and complications, particularly cyanosis, exercise intolerance, dyspnea upon exertion, etc..

• Rhythm disturbances, particularly atrial fibrillation, corresponds to clinical deterioration and right heart failure.

• According to historical data, patients with ES usually die between 30 and 35 years.

• However, survival to late adulthood has been reported

Second Congenital Heart Disease Natural History Study (1993)

• Demontrated that patients with ES can survive for several decades following diagnosis.

• In this study, 54% of 98 unoperated patients with ventricular septal defects and ES were alive 20 years after diagnosis

Kidd L, Driscoll DJ, Gersony WM, Hayes CJ, Keane JF, O’Fallon WM, Pieroni DR, Wolfe RR, Weidman WH. Second natural history study of congenital heart defects. Circulation 1993;87(suppl I):38-51.

WHY GOOD PROGNOSIS?1. RV appears to adapt to the rise in pressure

through hypertrophy and preservation of a fetal-like phenotype

2. Regression of the physiologic right ventricular hypertrophy does not occur and the right-to-left shunt serves as an excess flow valve

3. Ability of Eisenmenger patients to maintain their systemic CO at the expense of cyanosis

Eisenmenger SyndromeUnderlying Basic Lesions

Type of lesion Somerville’98(n=132) Daliento ’98(182)

Ventricular Septal Defect 45 71

Atrial Septal Defect 6 21

Patent ductus arteriosus 12 36

Atrio ventricular septal defect 16 23

Truncus arteriosus 15 11

Single ventricle 13 9Transposition of great arteries

5 8

Others 20 9

WHY EARLY ES IN POSTTRICUSPID SHUNT THAN ASD?

• POST TRICUSPID SHUNT (VSD/PDA)

• PVR never comes down to normal due to

high pressure flow from infancy

• Regression of medial hypertrophy of SMC &

RVH does not occur

• DVP PAH & reversal of shunt at an early age• PRETRICUSPID SHUNTS( ASD)• Direction of shunt is determined by the Right

ventricular compliance so no shunt occurs

till 3 months

• PVR reaches normal by 3 mths

• PAH & ES occurs late in life especially in a

large ASD

• PAH in ASD believed to be acquired or

unrelated to the defect

PAH associated with heart Defects with Decreased Pulmonary Blood Flow

• Condition likePA with intact IVSTOF

• Associated because of Hypoplasia of pulmonary arteries. Intra-acinar pulmonary arteries are small and few

in number. Alveolar development is impaired (mostly

reduction in alveolar number) ↑ Hematocrit resulting in in-situ thrombus.

Signs and Symptoms

1. Exertional dyspnea, 2. Lethargy, and 3. Fatigue,

In ability to increase cardiac

output

1. Exertional chest pain (ie, angina), 2. Exertional syncope, and 3. Peripheral edema

The PH progresses and right ventricular failure develops.

Right ventricular wall stress Myocardial oxygen demand

Subendocardial hypoperfusion

Angina

Dynamic compression of the left main coronary artery by an enlarged pulmonary artery(if PA > 40mm)

CLINICAL FEATURES

COMPLICATION FREQUENCY1. HAEMOPTYSIS 20%

2. PULMONARY THROMBOEMBOLISM 13%

3. STROKE 8%

4. CEREBRAL ABSCESS 4%

5.I.E 3%

SYMPTOM FREQUENCY

D.O.E 84%

INCREASED CYANOSIS 59%

HYPERVISCOSITY 39%

ANGINA 13%

SYNCOPE 10%

CHF 8%

Signs and Symptoms• Passive hepatic congestion may cause

anorexia and abdominal pain in the right upper quadrant.

• Less common symptoms of PH include cough, hemoptysis, and hoarseness (ie, Ortner's syndrome) left recurrent laryngeal nerve compressed by a dilated main pulmonary artery.

• Dizziness or syncope • Lower extremity edema and eventually ascites • Cyanosis of the lips and skin

CYANOSIS & CLUBBING in ES• Cyanosis• Most florid when the shunt was at ventricular level and least with a

patent ductus. • VSD -no case was truly acyanotic even at rest,42% had gross

cyanosis• PDA -60% of were acyanotic in the head and upper extremities. only

4% had gross cyanosis,differential cyanosis-50%

• Clubbing • PDA -absent in 76% of the cases ,considerable in only 5%; • VSD-Absent 3% and gross 36%. • ASD-Intermediate

• Squatting - uncommon • Relatively more frequent with ventricular septal

defect (15%) than with atrial septal defect(5%) or patent ductus (3%)(p.Wood)

PHYSICAL FEATURES• Pulse-small about twice as often with atrial

septal defect (88%) as with ventricular septal defect (37%) or patent ductus (50%).

• When full or water-hammer in quality, atrial septal defect was never present

• Bidirectional aorto-pulmonary shunts -water-hammer pulses (12%)(p.wood)

• Jugular Venous Pressure: small dominant a wave measuring about 3 mm. Hg 20 to 25% of cases of each type.

• Large v waves from tricuspid incompetence in 5% of all cases

• RV impulse palpable in ASD(57%),rare with VSD/PDA• An impulse over the pulmonary -66% of cases in each

group.• Right atrial gallop -38% of cases with interatrial shunt,

but in only 2 to 3% of the others• Pulmonary ejection click -in about two-thirds of all

cases• Functional pulmonary ejection murmur, usually of

moderate intensity and relatively short duration, -80% of all cases, -loud in 25%

• Thrill - one-half of the loud murmurs,10% overall

S2• ASD –wide fixed,never single• VSD –single (55%),wide varying(12%)• PDA –narrow/wide

varying(50%),single(6%)

• Auscultation of the heart may also reveal a systolic ejection murmur and, in more severe disease, a diastolic pulmonic regurgitation murmur.

• The right sided murmurs and gallops are augmented with inspiration

• Right ventricular failure results in systemic venous

hypertension.

• This can lead to findings such as elevated jugular venous

pressure, a right ventricular third heart sound, and a high-

pitched tricuspid regurgitant murmur accompanied by a

prominent V wave in the jugular venous pulse if tricuspid

regurgitation is present.

• In addition, hepatomegaly, a pulsatile liver, peripheral edema,

and ascites may exist.

Work up Imaging tests are useful in 1. detection of PH , 2. assessment of severity of PH, 3. categorization – the specific group the patient belongs to, 4. prognostication , 5. serial followup of patients( those who receive PH specific therapies)

ECG• RVH – tall R in v1 , R/S >1 , monophasic R or qR• Right atrial abnormality – tall peaked P in lead 2• RIGHT axis deviation• Secondary ST- T Changes in V1- V4.• RBBB – uncommon manifestation• RVH ± RAD is present nearly 90% of patients.• A normal ECG is reported in <5% cases.

RBBBExtreme right axis deviation (+180 degrees)S1 Q3 T3T-wave inversions in V1-4 and lead IIIClockwise rotation with persistent S wave in V6

Right axis deviation.T-wave inversions in V1-4 (extending to V5).Clockwise rotation with persistent S wave in V6.

• The rhythm is usually sinus , AF occurs rarely in patients with advanced RV disease and RV dysfunction.

• The annual risk of SVT is roughly 3%.• Ventricular arrhythmias are unusual.

CXR• It is abnormal in nearly 90% patients.• Enlarged MPA• Right pulmonary artery diameter > 14mm

in women , >16 mm in men.• Prunning – rapid tapering of peripheral

pulmonary arteries and increased translucency of peripheral lung fields due to hypovascularity.

 A right interlobar pulmonary diameter of greater than 16 mm or a hilar-to-thoracic ratio of greater than 0.44 is specific but not sensitive for the diagnosis of pulmonary hypertension.

• Cardiomegaly with right atrial and right ventricular enlargement usually present.

• Right atrial appendage dilatation results in obliteration of retrosternal space in its upper part.

• Retrosternal space obliteration beyond its lower 1/3rd indicates RV dilatation.

CXR – clue to etiology…• Pulmonary venous hypertension – dilated

upper lobe veins , perivascular cuffing , ground glass appearance of lung fields , kerly B lines, thickened minor fissure.

• Shunt lesions – shunt at atrial and ventricular level may results in inconspicuous aorta , shunt at arterial level leads to dilated ascending aorta.

• Lund parenchymal diseases – ILD , COPD.• Chronic thromboembolic PH- focal

hypovascularity • Congenital absence of a pulmonary artery.

• Lateral chest radiograph shows filling of the retrosternal airspace, a result of right ventricular dilatation.

• The right ventricle is in contact with more than one-third of the distance from the sternodiaphragmatic angle to the point where the trachea meets the sternum.

Echocardiographic Assessment• Echocardiography with Doppler studies is the most useful

first line investigation in a patient presenting with clinical features suggestive of pulmonary hypertension.

• It facilitates:1)    Estimation of pulmonary artery systolic pressure to

determine if PH is present.2)    Assessment of cardiac cause of PH3)    Assessment of severity of RV dysfunction4)    Assessment of prognostic variables

• Pulmonary valve  M-Mode

• According to Wyeman  the following M mode signs are useful in diagnosing PAH.

1. Diminished or absent a2. Presence of mid-systolic closure or notching3. Fluttering of the posterior pulmonic leaflet

M-mode of the pulmonary valve showing rectification of diastolic curve and lack of an atrial contraction dip in pulmonary hypertension patients (A). The mid-systolic dip (arrows), which is a specific (although low-sensitivity) sign of significant pulmonary hypertension, can be observed in

the lining of the pulmonary valve during the systolic phase (B).

• These findings generally manifest in moderate to severe PH.

• In pts with PAH ,colour reversal in MPA is a common finding.

• Early systolic forward flow along the lateral wall with subsequent late systolic flow

Pulsed wave Doppler in the pulmonary artery showing rapid early systolic acceleration and mid-systolic slowing.

Estimating Pulmonary Artery Systolic Pressure

• Echocardiographic evaluation of pulmonary artery systolic pressure (PASP) relies on the fact that PASP approximates right ventricular systolic pressure (RVSP) in the absence of right ventricular outflow obstruction.

• The most accurate echocardiographic method for estimating (PASP) uses the simplified Bernoulli equation to obtain a systolic trans-valvular pressure gradient.

• DPRV-RA = 4(VTR)2

• Where VTR is the velocity of the tricuspid regurgitant jet. This figure is added to an estimate of right atrial pressure (RAP) to produce an estimate of RVSP.

• PASP » RVSP = 4(VTR)2 + RAP

ESTIMATION OF RAP• Qualitative Features that suggest elevated

RAP in ECHO – 1. RA enlargement2. Persistent bowing of atrial septum toward

left atrium3. Dilated coronary sinus4. Dilated IVC and hepatic veins.

Other methods to asses RAP• Ratio between Tricuspid valve E velocity

and tricuspid annulus tissue doppler velocity E’ .

• If the ratio is >6 , RAP of >10 mmhg is predicted with a sensitivity of 79% and specificity of 87.7%.

Hepatic vein (HV) flow velocities• The HV flow velocity profile consists of 4 components,

2 in forward flow and 2 in flow reversal, each with a systolic and diastolic component (S, D and SR, SD).

• The velocities reflect changes in right atrial pressure and compliance, analogous to the pulmonary vein flow velocity changes for the left atrium.

• Normally, there should be no prominent reversal of velocities and S is higher than D.

• As RV filling pressure increases, flow reversal in systole and diastole becomes prominent and is augmented by inspiration.

• HV diastolic flow reversal is seen in PH and constrictive pericarditis. Respiratory variation helps differentiate between them.

• It is augmented with expiration in constriction, whilst in PH it remains constant.

• Hepatic venous systolic filling fraction -

VTI of systolic flow/ systolic +diastolic flow VTI

• A Value of<55% is suggestive of RAP being heigher than 8mmhg with a sensitivity of 86% and specificity of 90%.

• ESTIMATION of PAP in pts without PR /TR

• Comprises nearly 15% of pts• RV IVRT/HR >65 ms identifies those with

PASP >40 mmhg.• But if RA pressure is high ,IVRT may be

shorter despite pumonary hypertension.

PUMONARY ARTERY ACCELERATION TIME

• In normal individuals, AcT exceeds 140 milliseconds and progressively shortens with increasing degrees of pulmonary hypertension.

• The shorter the acceleration time, the higher the pulmonary artery pressure.

MEAN PAP• The mean pulmonary artery pressure can also be

estimated by Doppler. • Mpap = 0.61 × spap + 2mmhg• Mpap = 4 × early diastolic PR velocity• MPAP= 4× mean velocity of TR +RAP• MILD PAH mpap – 25 to 40 mmhg • MODERATE - : 40 – 55 mmhg• SEVERE - : >55 mmhg

• Mpap = 79-(0.45×acceleration time)• If AT <120 ms ; Mpap = 90-(0.62×AT )• This method is relatively easy to perform,

highly reproducible, and unlike pressure estimates based on tricuspid regurgitation velocity, Doppler recordings from the RVOT are available in virtually all patients.

DIASTOLIC PAP• Dpap =( 4×end diastolic velocity of PR jet)

+ RA pressure• Dpap = 0.49 × SPAP • In cases where PR jet is not available , RV

pressure at the time of pulmonary valve opening from TR velocity spectrum can be used.

PVR• Pressures are flow dependent, so

assessment of disease severity cannot be reliably done from systolic pressure alone.

• Ex – pts with advanced PH , decreased RV function RVSP is lower than expected.

• In these situations calculation of PVR is more dependable.

• PVR= ( TR velocity/RVOT VTI) 10 0.16₊• A TRV/RVO VTI cutoff value of 0.175 had

a sensitivity of 77% and specificity of 81% to determine PVR >2 WU.

• If >0.275 ,PVR of >6wu is very likely.• But this equation performed

poorly(underestimation) when PVR >8

• PVR = (RVSP – E/e’ )RVOT VTI• This equation performed better than the

previous one when compared to invasively measured PVR.

• LINDQVIST method- PVR= mPAP – PAWP / CO Mpap= PASP × 0.61+ 2 mmhg PAWP is assumed to be 10 mmhg CO = LVO VTI × CSA of LVOT × heart rate

PULMONARY VASCULAR CAPACITANCE

• A measure of proximal PA distensibility • PVCAP = stroke volume/ pulse pressure SV / 4 × (TRV2- PRV 2)A value of < 0.8ml/mmhg predicts higher

mortality in PAH.

Assessing Severity of RV Dysfunction

• Assessment of right ventricular function is the single most important aspect of the DE examination in patients with known or suspected PVD

• As the morbidity and mortality associated with this condition is heavily dependent on the degree of adaptation of the right ventricle to its excessive pulmonary vascular load.

• The right ventricle is better suited for volume work.

• When there is afterload mismatch RV dilatation is seen.

• When RV dilates it assumes a bullet shape in A4C view and circular in SAX view.

• SYSTOLIC FLATTENING OF IVS• Degree septal bowing is quantified by measuring LV

• ECCENTRICITY INDEX.• Normally LV is circular in both systole and diatole ,with

both vertical and horizontal dimensions of the cavity is equal.

• Normal index is 1.• Mild septal flattening – 1.1 to 1.4• Moderate – 1.5 to 1.8 • Severe - >1.8

TAPSE• TAPSE can be derived from 2D echo or M-

Mode , is simple to perform and has been shown to be highly reproducible, owed in part to the lack of reliance on RV endocardial definition or geometric assumptions.

• Ghio et al. recently showed in a PAH cohort that a TAPSE≤1.5 cm was associated with a nearly three-fold higher event rate (death or emergent lung transplant) versus subjects with a TAPSE>1.5 cm.

TDI• Tissue Doppler imaging (TDI) can also be used to

measure the velocity of RV contraction in the longitudinal axis (denoted S’ or Sa), correlates with TAPSE (r=0.90), and is another simple and reproducible method of RV function assessment.

• An S’ <10 cm/sec predicts a cardiac index <2.0 l/min/m2 with 89% sensitivity and 87% specificity.

• In addition, the RV TDI signal can be integrated to measure the longitudinal tissue displacement.

TEI index• The myocardial performance index (MPI or Tei-Doppler

index) uses a different approach to RV function assessment, integrating systolic and diastolic function parameters in a single measure.

• the formula IVRT+IVCT/RVET, where IVRT is the RV isovolumic relaxation time, IVCT is the isovolumic contraction time, and RVET is the RV ejection time.

• The time intervals are typically derived from tissue Doppler signals.

• Increasing values represent worsening function, with an increased RV MPI associated with decreased survival in PAH.

Doppler Echocardiography

• Normal value is 0.28 ± 0.004• It is prolonged in RV dysfunction.• The upper reference limit is 0.40 by pulsed

doppler and 0.55 is by tissue doppler.• Limitation – it is load dependent and may

get pseudonormalized if RA pressure are high.

RV SIZE• The normal RV measures approximately 2.5–3.5 cm at end-

diastole, with a planimetered area of 15–18 cm2.

• Typically, the RV dimension and area are two-thirds that of the LV.

• The normal RV:LV ratio is approximately 0.6–0.8, with increasing RV:LV ratios in patients with mild (0.8–1.0), moderate (1.1–1.4), and severe (≥1.5) RV dilatation.

• A useful rule of thumb: RV:LV ratio should be <1.0,

• Value >1.0 : strongly suggestive of RV dilatation, often coinciding with RV dysfunction.

RVFAC• A more quantitative approach is to measure the

total systolic area change of the RV, referred to as the RV fractional area of change (RVFAC).

• This measure is derived from the planimetered areas of the RV at end-diastole and end-systole ([RVFAC=RV Area ED-RV areaES/RV AreaED] × 100) from the apical four-chamber view.

• Normal value is 56 ± 13.• A value of <40% implies RV dysfunction.• The RVFAC does not require geometric assumptions

and correlates with the RV ejection fraction. • However, incomplete visualization of the RV cavity

(more common in the setting of RV enlargement) as well as suboptimal endocardial definition lead to relatively high inter- and intra-observer variablility.

STRAIN and STRAIN RATE• 2D strain using speckle tracking method is

likely to be more sensitive to detect early RV dysfunction.

• Normal strain rate at base : 1.5 -1.74 mid cavity :1.46 – 1.62• Normal value for strain : 25% -33%

Echocardiographic Assessment of Cardiac Causes of Pulmonary Hypertension

• The most common cause of pulmonary hypertension is left sided heart disease resulting in venous pulmonary hypertension.

• Echocardiography allows for assessment of left ventricular systolic and diastolic dysfunction as well as left sided valvular disease and congenital heart disease.

PERICARDIAL EFFUSION• In the setting of PAH, a mild to moderate circumferential pericardial

effusion is seen in up to half of patients.

• In general, a pericardial effusion typically indicates right heart decompensation, and is likely conferred on the basis of longstanding right atrial hypertension and impaired myocardial lymphatic drainage.

• The presence of a pericardial effusion has been one of the most consistent echocardiographic findings indicative of a poor prognosis in PAH.

• Percutaneous or surgical pericardial drainage should be avoided unless there is especially compelling evidence of tamponade, as the effusion typically is the result (not the cause) of RV failure and right atrial hypertension

PROGNOSTIC FACTORSBest predictors of poor outlook 1.RA size- RA area index change of 5 cm2/m2. Pericardial effusion 3. Degree of interventricuar septal shift

• MPAP >49 mmhg • Dpap >29 mmhg• Abnormal end diastolic septal curvature• IVC >2cm with <50% inspiratory collapse• TEI index >0.98• TAPSE

CT CHEST• Plays an important role in diagnosis of

certain causes of PH.• CT findings in PH –• 1. diameter of MPA > 29mm• 2. MPA/ ascending thoracic aorta >1• 3. A segmental artery to bronchus

diameter ratio > 1 in three or four lobes.• 4. distensibility of PA <16.5%

 the pulmonary artery measures 41 mm in diameter

• Cardiac changes – • 1. RVH – wall thickness >4 mm• 2. RV dilatation – RV/LV diameter ratio >1

at midventricular level on axial images.• 3.straightening or leftward bowing of IVS• 4. reduced RV EF• 5.dilated IVC / HEPATIC VEINS.

• MOSAIC pattern of lung attenuation – 77% of pts with CTPH and 12% of IPAH patients.

• Regions of hyperemic lung and adjacent regions of oligemic lung.

• Other diseases – small airway diseases and infiltrative lung diseases.

CT PULMONARY ANGIOGRAM• Useful in imaging the vascular changes that typically

occur in CTPH.• The central Pas are dilated , luminal irregularities by

organized thrombus, rat tail appearance of PA branches ,bands ,pouches, webs or flaps, stenosis, post stenotic dilatation and tortuosity.

• The sensitivity and specificity is 98 and 95% at lobar level and 94% and 93% at segmental level with reference to invasive angiography.

eccentrically located thrombus that forms obtuse angles with the vessel wall 

 peripheral wedge-shaped area of hyperattenuation in the lung (arrow), a finding that may represent an infarct, as well as a linear band (arrowhead).

FUNCTIONAL STATUS ASSESMENT

• Exercise testing O2 consumption-<10.4ml/min/m2 associated with poor prognosis

• 6 minute walk test-simple test-detect exercise desaturation,functional assessment

CARDIAC CATHETERISATIONIndications • Not required for diagnosis

• It must be done in borderline cases to assess operability

• Response of pulmonary vasculature to pulmonary

vasodilators like 02, tolazoline and nitric oxide should be

assessed

PRECAUTIONS WHILE DOING CATH• Polycythemia

– PCV of >65% =Phlebotomy (O-D/O x wt x70)• Anaemia

– Appropriate Hb =38 –(0.25 xSaO2)• Contrast use

– Less than 4ml/kg

HEMODYNAMICS IN ES VS PPH• ES had greater pulmonary artery pressures (107

+/- 20 versus 97 +/- 21 mm Hg, p = 0.06)• Patients with Eisenmenger syndrome had

greater systemic cardiac indexes (2.7 +/- 0.6 versus 2.2 +/- 0.8 L/min/m2, p < 0.05) and lower mean right atrial pressures (5 +/- 2 versus 12 +/- 5 mm Hg, p < 0.0001) than patients with primary pulmonary hypertension

Hopkins et al,Comparison of the hemodynamics and survival of adults with severe primary pulmonary hypertension or Eisenmenger syndrome.J Heart Lung Transplant. 1996 Jan;15(1 Pt 1):100-5

DETERMINING REVERSIBILTY

• Absolute PVR >12 ASD,>8 VSD,>7 PDA• PVRI/SVRI Ratio <0.25 =operable 0.25-0.5 –operable,mild risk 0.5-0.75 – operable with high risk of post op PAH >0.75 - Unoperable• PASP >80% SBP• PA mean >50% Sytemic mean

NO LONGER APPLICABLE

VASODILATOR TESTING

FAVOURABLE PARAMETER FOR ICR

PIT FALLS• Reversibility seen in <10%• Hemodynamic guidelines to ensure postoperative

success and long-term survival without pulmonary hypertension are still not precise.– Lock et al(1982) showed that in large VSD with PAH, fall in

PVR/SVR by >30% did not correlate with operative survival or late PVR/SVR.

– Moller (1991) showed closure of VSD with high PVR of >7 WU had higher operative and long term mortality.

– Kannan et al (2003)showed that 21% of those who showed vasoreacitivity had poor outcome with persistent PAH

• Technical difficulties leading to calculation errors and other medical conditions need to be considered

• Vishwanath S,Kumar.Assessment of operability of congenital cardiac shunts with increased PVR;CCI 2008

• Controversy whether testing at maximal stimulation (90% O2 and 80 parts per million of iNO) or a conservative intermediate protocols (O2 21–30%, iNO 40 PPM) or gradual increases in vasodilator challenge would be better predictors.

PIT FALLS• However, advanced therapies for PAH have a

combined vasodilative and antiproliferative effect. • Thus, there is also evidence to suggest that the

pulmonary hemodynamics and the clinical status may improve irrespective of the response to acute vasodilator testing.

• Absent or a negative pulmonary vasoreactivity study should not preclude initiating disease-targeting therapy.

Pulmonary wedge angiography • For the right-sided

angiogram, a 5F or 6F pulmonary wedge catheter was placed in the lower lobe to a level one rib space below the takeoff of the right pulmonary artery.

• For the left-sided studies, the catheter was placed two rib spaces below the takeoff of the left pulmonary artery.

• After the catheter was positioned, the balloon was inflated and contrast material was injected at a dose of 0.3 ml/kg (minimum 2 ml).

• Injections were by hand as this was thought to be safer and simpler

Analysis of the Angiogram• Tapering • AP view• Maximum expiration• Arterial lumen diameter 2.5 &1.5mm

noted.• The length of the artery between the two

diameters is measured for as many no. of vessels as possible

• Average taken.

Rate of Tapering

• The length of the artery segment between the two diameters reflected the rate of tapering of the artery (the longer the segment, the more gradual the tapering; the shorter, the more abrupt).

• Background Haze• The degree of filling of small peripheral

arteries that determines the background haze.

• The degree of background haze was assessed as being normal, mildly, moderately or markedly reduced by comparing the angiogram with standard normal angiograms.

• Arterial concentration is reduced in newborns and young infants.

• In patients younger than 6 months of age, mild or moderate reduction was considered normal, and in younger than 1 year of age mild reduction was considered normal.

• Reduced background haze in patients with PAH.

• Pulmonary Circulation Time:• Pulmonary circulation time as the transit

time of the contrast material through the capillaries and veins.

• Measured by counting the number of frames between the time the balloon was deflated and the time contrast material was seen in the pulmonary veins at their site of entry into the left atrium.

• This is divided by the frame rate of the cine film

• Longer the circulation time severe the pulmonary vascular disease.

• Quantitative assessment from a pulmonary wedge angiogram of the rate of tapering of the pulmonary arteries is useful in patients with congenital heart disease who have, or are at risk of developing, severe pulmonary vascular changes and fixed elevation in pulmonary vascular resistance.

• More abrupt arterial tapering is more suggestive of severe changes in the distal pulmonary vascular bed

Management • Pharmacological therapy• Conventional therapy • Anticoagulation• CCB’s• Prostacyclins• Endothelin receptor antagonists• PDE inhibitors• Novel therapies

Novel therapies

Riocigaut

fasudil

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