HISTORY

34-year-old woman.

CHIEF COMPLAINT: Progressive exercise intolerance of eighteen

months duration.

PRESENT ILLNESS: In addition to diminished exercise tolerance, she has

poorly localized chest pain with exertion which is relieved by rest. Last month

while walking up a flight of stairs she nearly “passed out.”

Her growth and development were normal. No murmurs have been described

in the past. She delivered her third child four years ago, and has had no

problem with her pregnancies.

Question: What diagnoses are suggested by this history?

11-1

Answer: The history is consistent with pulmonary arterial hypertension of

which there are four basic causes:

1. Outflow obstruction, e.g., mitral stenosis

2. Shunt lesions, e.g., ventricular septal defect

3. Vascular lung disease, e.g., multiple emboli

4. Airway lung disease, e.g., chronic bronchitis

The lack of orthopnea or nocturnal dyspnea is against mitral stenosis, and the

lack of a previous murmur is against both mitral stenosis and a shunt lesion.

However, when pulmonary hypertension is severe, the diagnosis may be

difficult to define.

Proceed

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PHYSICAL SIGNS

a. GENERAL APPEARANCE - Slightly dyspneic 34-year-old woman.

b. VENOUS PULSE - The CVP is estimated to be 12 cm H2O.

Question: How do you interpret the venous pulse?

JUGULAR

VENOUS

PULSE

ECG

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Answer: The central venous pressure is elevated and there is a giant “a”

wave (arrow), reflecting an enhanced right atrial contraction as it pumps against

an increased resistance to outflow.

c. ARTERIAL PULSE - (BP = 90/70 mm Hg)

Question: How do you interpret the arterial pulse?

CAROTID

1.0 SECOND

ECG

Answer: The arterial pulse is diminished, as is the patient’s pulse pressure.

This suggests either low cardiac output, obstruction to outflow at the valve level

or obstruction in the pulmonary circulation.

Proceed

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d. PRECORDIAL MOVEMENT

Question: How do you interpret the precordial movements?

ECG

UPPER RIGHT

STERNAL EDGE

MID-LEFT

STERNAL EDGE

UPPER LEFT

STERNAL EDGE

.20 sec.

200

CPS

S1 S2

Answer: There are a palpable fourth sound and a sustained systolic

impulse in the third and fourth interspaces, and a separate systolic impulse in

the second interspace. These movements are typically found when the right

heart is severely after-(pressure) loaded, as the pulmonary artery and right

ventricle dilate and hypertrophy. Note there is no separate apical impulse,

suggesting the enlarged right ventricle occupies the apex.

Proceed

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11-8

e. CARDIAC AUSCULTATION

Question: How do you interpret the acoustic events at the upper left

sternal edge?

ECG

S1 S2 PHONO-

CARDIOGRAM

(Pulmonic Area)

CAROTID

EXPIRATION INSPIRATION

S1

S2 S1

S2

Answer: There is a late occurring pulmonary ejection sound (approximately

.06 seconds after S1). The higher the pulmonary resistance and the slower the

rate of the right ventricular contraction, the later the ejection sound. It is the

only right-sided event which may be selectively increased with expiration.

There is a short crescendo-decrescendo systolic murmur increased during

inspiration. Since it occurs only during maximum flow across the pulmonary

valve, it is likely due to turbulence in a dilated pulmonary artery.

The pulmonary second sound is increased and obscures the sound of aortic

closure. With greater right ventricular failure, it may be delayed, and wide

persistent splitting may result.

Proceed

11-9

Answer (continued): There is a diastolic murmur of pulmonary

regurgitation due to pulmonary hypertension. The high diastolic pressure

exerted on the incompetent pulmonary valve throughout diastole accounts for

its early onset, high frequency, decrescendo configuration and length in

contrast to patients with congenital pulmonary regurgitation. The murmur per

se is therefore very similar to that heard in aortic regurgitation. These concepts

are demonstrated on the pressure curves of the pulmonary artery (PA) and

right ventricle (RV) which follow.

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THE DIASTOLIC MURMUR

Though a right-sided fourth sound was

readily palpated, it was not audible due

to its very low frequency. If functional

tricuspid incompetence occurs, a

holosystolic murmur may be heard,

especially during inspiration as right

heart filling is augmented, and may be

associated with a right-sided third sound.

f. PULMONARY AUSCULTATION

Question: How do you interpret the

acoustic events in the pulmonary lung

fields?

Proceed

100

PA

RV

DM

P2 S1

0

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11-12

Answer:

In all lung fields, there are normal vesicular breath sounds.

ELECTROCARDIOGRAM

Question: How do you interpret this ECG?

I II III aVR aVL aVF

V1 V2 V3 V4 V5 V6

NORMAL STANDARD

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Answer: The ECG shows right atrial enlargement, right axis deviation and

right ventricular hypertrophy. The ST segment and T wave changes are

consistent with right ventricular strain.

CHEST X RAYS

Question: What abnormalities are seen in these chest X rays?

POSTEROANTERIOR (PA) LEFT LATERAL

Answer: The PA chest film shows an increased cardiothoracic ratio with

marked prominence of the main pulmonary artery and its branches. The

enlarged right ventricle forms an acute angle with the diaphragm, and a dilated

right atrium forms a convex sweep along the lower right cardiac border. The

peripheral lung fields are radiolucent. The lateral film shows the right ventricle

filling the retrosternal space, implying it is enlarged, although chest

configuration alone may cause this apparent change in some patients.

Question: Based on the history, physical examination, ECG and chest

X rays, what is your initial diagnostic impression and plan to further evaluate

the patient?

11-14

Answer: Based on the history, physical examination, ECG and X rays, the

patient has severe pulmonary arterial hypertension of unknown cause. Further

evaluation to determine a potentially treatable lesion is mandatory, as the

prognosis and treatment of the pulmonary hypertension depends on the

etiology. Efforts should specifically be directed at detecting unrecognized and

potentially treatable thromboemboli, a shunt lesion or mitral stenosis.

Question: What non-invasive procedure may be helpful in differentiating

between pulmonary thromboemboli and primary pulmonary hypertension?

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Answer: A ventilation perfusion lung scan. The patient’s study follows.

Question: What is your interpretation of the lung scan?

LUNG SCAN

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Answer: The patient’s perfusion lung scan shows symmetric distribution of

small areas of hypoperfusion, as is typically seen in primary pulmonary

hypertension. In patients with pulmonary emboli, the lung scan typically shows

asymmetric large defects corresponding to pulmonary segments and

subsegments as shown below.

Question: What non-invasive procedure may be helpful in assessing mitral

stenosis as a cause of the patient’s pulmonary hypertension?

11-17

Answer: Since the diagnosis of primary pulmonary hypertension has a poor

prognosis, further study is indicated. A two-dimensional echo Doppler can be

used to estimate pulmonary artery pressure, more precisely locate the source

of the high frequency diastolic murmur, quantitate ventricular size and

function, detect an intracardiac shunt and exclude mitral stenosis and other

causes of secondary pulmonary hypertension.

Patients with pulmonary hypertension may require a diagnostic catheterization

study to establish the severity of the pulmonary hypertension, and exclude

secondary causes. The patient’s study follows.

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LABORATORY

Cardiac catheterization revealed no shunt lesion. Mild arterial desaturation was

found, but breathing 100% O2 resulted in full saturation. The wedge pressure

was normal.

Question: How do you interpret the catheterization data?

100

Aorta

Left

Ventricle Pulmonary

Artery

Left Atrium 0

80

60

40

20

Answer: The pulmonary artery pressure is at systemic levels. There is no

mitral gradient. There is no shunt lesion, and left ventricular filling pressure is

normal. The mild arterial desaturation is due to the patient’s pulmonary disease

per se, as it was reversed by 100% O2.

Although not indicated in our patient, when the lung scan is suggestive of

thromboembolism, a pulmonary angiogram should follow the catheterization

study. A representative study follows.

Proceed

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LABORATORY (continued)

MAIN PULMONARY ARTERY ANGIOGRAM

Questions:

1. How do you interpret the patient’s pulmonary angiogram?

2. How would you treat this patient?

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Answers:

1. The pulmonary angiogram reveals marked dilation of the main and

proximal right and left pulmonary arteries. The peripheral pulmonary

arteries taper rapidly and the vascularity of the outer one-third of the lung

field is decreased (a “pruned tree” appearance). There are no filling

defects. Opacification of the right ventricular outflow tract (arrow) due to

pulmonic insufficiency is evident. The levo phase (not shown) revealed no

pulmonary venous obstruction. The angiogram is compatible with severe

primary pulmonary hypertension.

A short-acting vasodilator challenge should also be part of the initial

catheterization study and is used to evaluate pulmonary vasodilatory

response. A positive response to the vasodilator challenge predicts those

patients who will benefit from a long-acting oral vasodilator while a

negative response predicts those who will benefit from chronic IV

prostacyclin. This patient had a positive response to the challenge.

2. The patient was treated with a long-acting oral calcium channel blocker

and anticoagulation to prevent in situ thrombosis. This treatment regimen

has been shown to improve symptoms, exercise tolerance and survival. If

the patient develops progressive symptoms in the future, she will be

considered for lung transplantation.

Proceed for Summary

SUMMARY

Primary pulmonary hypertension is a syndrome resulting from intrinsic,

idiopathic and progressive obstructive disease in the small terminal arteries and

arterioles of the pulmonary vascular bed. Early in the natural history,

vasoconstriction contributes to elevated arteriolar resistance, which ultimately

becomes fixed and non-vasoreactive. Due to the increased resistance to flow

through the lungs, pulmonary artery pressure rises, and cardiac output,

especially with exercise, drops. Ultimately, right ventricular hypertrophy and

failure occur.

The disease is twice as common in women as in men, and occurs especially

between the ages of 20 and 50. Death commonly occurs within five years after

symptoms appear, if the patient is untreated. This syndrome may be familial.

Proceed

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The typical histopathology of primary pulmonary hypertension is shown below.

There is marked intimal cellular proliferation and medial hypertrophy of the

arteriolar wall. A bronchiole lies to the right of the arteriole.

The above changes may progress to necrotizing arteritis. Since in situ thrombi

are commonly seen, this syndrome may be pathologically as well as clinically

indistinguishable from recurrent small multiple pulmonary emboli.

Proceed for Case Review

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To Review This Case of

Primary Pulmonary Hypertension:

The HISTORY is typical, including exercise intolerance and effort syncope

due to low fixed cardiac output, in a patient with no previous murmur. Chest

pain resembling angina may be due to inadequate coronary flow in the face of

an acutely stressed hypertensive right ventricle.

PHYSICAL SIGNS:

a. The GENERAL APPEARANCE reveals a slightly dyspneic woman in her

30’s.

b. The JUGULAR VENOUS PULSE mean pressure is elevated at

12 cm H2O and reflects the increased right atrial filling pressure caused by

the thickened, less compliant right ventricle. The wave form shows a giant

“a” wave from an increased atrial contraction.

c. The CAROTID ARTERIAL PULSE is diminished due to obliterative

obstructive pulmonary disease associated with diminished cardiac output.

d. PRECORDIAL MOVEMENTS reveal a palpable pulmonary artery and

a presystolic and sustained right ventricular impulse.

e. CARDIAC AUSCULTATION reveals classic findings of pulmonary

hypertension. The pulmonic component of the second sound is very loud,

obscuring the sound of aortic closure. Although it was palpated, no fourth

sound is heard due to its very low frequency. There is a prominent ejection

sound which selectively diminishes on inspiration. There is an early systolic

“flow” murmur due to turbulence in the dilated pulmonary artery during the

maximum flow, and a diastolic decrescendo murmur of pulmonary

incompetence associated with severe pulmonary hypertension. Both

murmurs are increased during inspiration, as right-sided filling is

augmented by the drop in intrathoracic pressure.

Proceed

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f. PULMONARY AUSCULTATION reveals normal vesicular breath

sounds in all lung fields.

The ELECTROCARDIOGRAM shows right atrial enlargement,

right axis deviation and right ventricular hypertrophy and “strain.”

The CHEST X RAYS show radiolucent peripheral lung fields,

pulmonary artery enlargement, and right atrial and ventricular enlargement.

LABORATORY STUDY with non-invasive techniques reveals a

LUNG SCAN typical of primary pulmonary hypertension.

The ECHOCARDIOGRAM is classic for pulmonary hypertension, but more

importantly, essentially excludes mitral stenosis.

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CARDIAC CATHETERIZATION confirms severe pulmonary hypertension

with systemic pressure in the pulmonary artery, and excludes mitral stenosis

and shunt lesions.

PULMONARY ANGIOGRAPHY reveals a classic “pruned tree” appearance

of the pulmonary arteries without filling defects of large pulmonary emboli,

confirms the patient’s pulmonary insufficiency, and excludes pulmonary venous

obstruction. The patient had a positive response to the vasodilator challenge.

The TREATMENT for primary pulmonary hypertension is evolving and

includes vasodilators and anticoagulants. Refractory patients may be

candidates for lung transplantation.

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