Cardiology Core Curriculum A problem-based approach - part 8 pps

The sustained increases in right ventricular Table 14.1 Primary pulmonary hypertension versus recurrent pulmonary embolism Recurrent pulmonary Similarities Symptoms Fatigue, dyspnea on e

Answer to question 2 Figure 13.12 shows a magnetic resonanceangiogram of the thoracic cavity In this angiogram, rapid blood flow

is recorded as lighter shading while slower flow is indicated in darkertones The heart is anterior in this photo (blurred due to motionartifact), and the descending aorta is located posteriorly Within theaorta a partition is visualized, which is the intimal “flap” of thedissection On one side of the flap normal blood flow is present and

is the lighter of the two zones This represents the “true lumen” of theaorta The “false lumen” is the channel created by the dissectionprocess within the media of the aorta and is the darker of the twozones

This patient subsequently underwent contrast aortography(Figure 13.13) The thoracic angiogram shows the catheter in the

“true” aortic lumen In this study the entire length of the dissection

is visualized from its origin just above the aortic valve to its distalaspect within the descending aorta Also note the opacification of theleft ventricle, which indicates aortic regurgitation through anincompetent aortic valve These studies show this to be a proximal(type A) dissection with involvement of the ascending aorta as well asthe arch and descending aorta

Answer to question 3 The ideal study would be one that is readilyavailable, quickly performed, sensitive for the diagnosis of dissectionanywhere along the aorta, able to identify the site of intimaldisruption (which determines the surgical approach), and can identifyconcomitant aortic regurgitation or pericardial effusion Historicallythe “gold standard” for the diagnosis of aortic dissection has thereforebeen invasive catheterization and angiography However, the newernon-invasive modalities are highly sensitive and often eliminate theneed for angiography These include magnetic resonance imaging,transesophageal echocardiography, and computed tomography.Although the positive and negative predictive values favor magneticresonance imaging over the other non-invasive imaging studies (seeTable 13.3), the use of magnetic resonance imaging in this settingmay be limited by the long image acquisition time In addition,for critically ill patients magnetic resonance imaging is not practicalbecause it is impossible to attach intravenous infusion pumps withmetallic components or mechanical ventilators to the patient withinthe magnetic imaging field The advantage of transesophagealechocardiography is that it is usually readily available; it is portable,accurate, and quick to perform and interpret; and it is less costly thanmagnetic resonance imaging It can be used to detect aortic regurgitationand to assess ventricular function Computed tomography is alsosensitive and accurate, but suffers the disadvantages of its lack ofportability and the inability to assess aortic regurgitation Thus there are

clear trade-offs with any of these non-invasive techniques; therefore, ateach medical center the best diagnostic test for aortic dissection is theone that can be performed most rapidly and with the greatest localexpertise.

Answer to question 4 Once the diagnosis of a proximal aorticdissection is confirmed, the immediate management strategy is to callfor surgical consultation followed by emergent repair Medicalmanagement (antihypertensive and vasodilator therapy, as describedbelow) should not delay surgical intervention Ideally, surgicalevaluation should proceed in parallel with the diagnostic strategy ifthe initial differential diagnosis includes aortic dissection

For patients with a distal (type B) aortic dissection, the goal is tolower intra-aortic pressure and the force of ventricular contraction(dP/dt) in order to prevent further extension of the dissection This isinitially accomplished by the administration of intravenous

β-blockers (typically metoprolol or the short-acting agent esmolol), aswell as antihypertensive/vasodilator therapy using agents such asintravenous nitroprusside Once stabilized, oral β-blockers and otherantihypertensive agents can be substituted

Answer to question 5 Proximal (type A) aortic dissections should berepaired surgically to improve survival, whereas distal (type B) aorticdissections are treated medically with control of blood pressure asoutlined above However, there are exceptions to this rule Type Baortic dissections complicated by compromise of blood flow to vitalorgans, impending aortic rupture, or retrograde extension into theascending aorta should prompt surgical repair In addition, aorticdissections in all patients with Marfan’s syndrome should besurgically repaired because of the high incidence of redissection iftreated only with medications

The patient in this case underwent successful surgical repair of theascending aorta and replacement of the aortic valve, followed byaggressive long-term antihypertensive therapy

Heart tumors

Tumors of the heart are uncommon but can cause significantmorbidity, often in young individuals Tumors may be primary, butare more often metastatic from extracardiac sites Cardiac neoplasmsmay be asymptomatic Alternatively, they may result in aconstellation of findings due to their ability to act as space occupyinglesions and interfere with normal intracardiac blood flow, causepulmonary or systemic embolism, invade and destroy myocardial

tissue, and cause constitutional symptoms that mimic systemicillnesses.

Primary benign tumors of the heart

Approximately 75% of the primary tumors of the heart are benignand 25% are malignant Cardiac myxomas are the most commonprimary tumors, and are usually pathologically benign and curable ingeneral Myxomas, such as the one presented in the case history below,appear as large gelatinous, shiny, lobular masses, often severalcentimeters in diameter (Figure 13.14) Microscopically, they consist ofscattered stellate cells in a mucinous matrix They may arise from theendothelium of any cardiac chamber However, 75% of myxomasappear in the left atrium, approximately 20% in right atrium, and theremainder in the ventricles or on the surface of the cardiac valves Atrialmyxomas are most often pedunculated and 85% of the time arise fromthe fossa ovalis in the mid-atrial septum Myxomas appear as solitarylesions 95% of the time, and in the remainder multiple tumors arepresent Up to 10% of myxomas occur in a hereditary manner

The clinical relevance of cardiac myxomas is due to three features

of the tumor First, these are generally large, mobile, space occupyinglesions that can obstruct the inflow of blood to or outflow from thecardiac chamber in which they appear Second, friable tumorFigure 13.14 Gross pathologic specimen of a resected left atrial myxoma The tumor consists of a stalk with large gelatinous, shiny lobules

fragments or superimposed thrombi embolize to the systemiccirculation in 30–70% of patients with left atrial myxoma In a similarmanner, pulmonary embolism may result from emboli derived from aright atrial myxoma Finally, constitutional symptoms such as fever,chills, sweats, fatigue, and myalgias occur and may be related tonecrosis of portions of the myxoma or tumor secretory products.Left atrial myxomas may transiently obstruct blood flow across themitral valve during diastole Symptoms are intermittent and mayrelate to changes in body position due to the movement of the tumorwithin the chamber In such patients, episodic dyspnea, light-headedness and syncope often occur The physical examination of apatient with left atrial myxoma may demonstrate the stigmata ofperipheral systemic emboli and an abnormal cardiac examination Inearly diastole, a low-pitched “tumor plop” may be heard, as themobile tumor strikes the mitral valve or heart chamber wall If partialobstruction of transmitral flow ensues, then a diastolic murmurmimicking mitral stenosis can be heard In some cases, chronicrepetitive traumatic injury of the mitral valve by the myxoma mayresult in leaflet damage and the murmur of mitral regurgitation.Patients with right atrial myxoma may also manifest positionaldyspnea and syncope because of intermittent obstruction of thetricuspid valve In addition, symptoms typical of pulmonary embolimay result if there is dislodgement of tumor fragments Signs of rightsided heart failure may also appear, including jugular venousdistension, hepatomegaly, and peripheral edema A tall “a” wave may

be present in the jugular venous pulse if right atrial contraction causesthe tumor to partially obstruct blood flow across the tricuspid valve.Laboratory studies in patients with myxomas reveal anemia,leukocytosis, and an elevated erythrocyte sedimentation rate The

chest x ray film usually demonstrates a normal cardiac silhouette;

rarely, calcification within a myxoma may be visualized on the plainfilm The electrocardiogram may demonstrate left or right atrialenlargement, reflecting obstructed blood flow in the chamber thatcontains the tumor The most useful imaging modality istwo-dimensional echocardiography because myxomas are usuallyreadily identified using this technique (Figure 13.15) Although lessconvenient to perform, computed tomography and magneticresonance imaging have sensitivities of detection similar to that ofechocardiography

The curative treatment of an intracardiac myxoma is surgicalexcision Rarely, the tumor recurs (most often in the familial forms ofmyxoma), so that yearly echocardiography is recommended for

5 years following excision of the tumor

Cardiac myxomas have been reported as part of a syndromeincluding lentigines, blue nevi, and various endocrine abnormalities

(Cushing’s disease, acromegaly, testicular tumors, and myxoidfibroadenomas of the breast).

Other benign tumors of the heart are often asymptomatic, but theytoo may obstruct intracardiac blood flow or result in arrhythmiasand/or conduction disturbances Fibroelastomas are sometimes found

as an incidental finding on echocardiography They arise as smallmasses on the cardiac valves or adjacent endothelium They areseldom symptomatic, but occasionally interfere with valvularfunction Rhabdomyomas are the most common cardiac tumors inchildren They generally occur within the ventricles, are oftenmultiple, and depending on their size and location they may mimicvalvular stenosis, restrictive or hypertrophic cardiomyopathy, orresult in congestive heart failure Cardiac lipomas are often an

Figure 13.15 Echocardiogram, apical four chamber view, demonstrating a mass (M) extending between the left atrium (LA) and left ventricle (LV) RA, right atrium;

RV, right ventricle

incidental finding at autopsy Sometimes they become quite large andobstruct intracardiac flow or cause arrhythmias.

Primary malignant tumors of the heart

Primary cardiac malignant tumors are usually a form of sarcoma andappear more commonly in the right side of the heart Symptoms arisefrom intracavitary growth as well as invasion of the myocardium,conduction system, and pericardium Depending on the size andrate of progression, malignant cardiac tumors can result in suddencongestive heart failure, syncope, arrhythmias, and conductiondisturbances Myocardial invasion can result in electrocardiographicabnormalities that mimic acute myocardial infarction Erosion into thepericardium results in large hemorrhagic effusions In most cases,death occurs within weeks to months following initial presentation ofmalignant cardiac tumors Cures are uncommon, even with surgicaland radiation therapy Rarely, cardiac transplantation has beenperformed successfully Of the modalities available to image suspectedmalignant cardiac tumors, magnetic resonance stands out because itprovides superb anatomic detail that can delineate the extent of tumorinvasion and the relationship to normal cardiac structures

Metastatic tumors to the heart

Metastatic tumors to the heart are much more common thanprimary cardiac tumors They are found in 10% of patients who diefrom extracardiac malignancies, but they are rarely symptomaticduring life Cardiac metastases are most commonly found in patientswith cancer of the lung, breast, melanoma, leukemia, and lymphoma.Metastases arising from Kaposi’s sarcoma have been found in patientswith AIDS Metastatic cardiac tumors may invade the heart via theblood stream, the lymphatic system, or by direct invasion from theprimary neoplastic site Grossly, they may appear as small nodules or

as a diffuse infiltration into the myocardium and/or pericardium.When symptomatic, clinical findings are similar to those of primarycardiac malignant tumors Most commonly, symptoms are attributable

to pericardial metastasis with large malignant hemorrhagic effusions,which often result in cardiac tamponade Infiltrating tumor can alsoencase the heart and result in physiology resembling that ofconstrictive pericarditis

The prognosis of an individual with metastatic cardiac tumor ispoor, and therapy is generally palliative In rare cases, cardiac invasion

may respond to radiation or chemotherapy Acute deterioration due

to cardiac tamponade is treated by pericardiocentesis or, if recurrent,

by surgical creation of a pericardial window for continued drainage.Occasionally, certain carcinomas of extracardiac origin may extendinto the inferior vena cava and enter the right heart chambers via thatroute Such lesions are often readily visualized by echocardiography

or other imaging modalities Examples of such tumors include renalcell and hepatocellular carcinoma

Case studies

Case 13.3

A 22-year-old male college student and football player has been inpreviously good health Over the months before admission he notedintermittent low grade fever, fatigue, and decreased appetite Over the

2 weeks before admission he experienced repeated episodes of severelight-headedness and sudden dyspnea with rapid changes in position,such as jumping to catch the football The coach dismissed him fromthe football team because of his poor performance His mother,however, was not satisfied that a cause had been found for hissymptoms, and brought him to the hospital for evaluation His pastmedical history is unremarkable He is a non-smoker, non-drinker,and denies use of illicit drugs

Examination Physical examination: the patient appeared tired No

peripheral stigmata of embolic phenomena Temperature: 99°F(37·2°C) Weight: 200 lb (90·6 kg) Pulse: 64 beats/min, regular,normal sinus rhythm Blood pressure: 120/80 mmHg Jugular venouspulse: 5 cm Cardiac impulse: normal First heart sound: normal.Second heart sound: splits normally on inspiration In the left lateraldecubitus position, at the apex, an intermittent early diastolic lowfrequency sound was heard, which was followed by a brief diastolicmurmur Chest examination: normal air entry, no rales or rhonchi.Abdominal examination: soft abdomen, no tenderness Normal liverspan No other obvious abnormalities No peripheral edema Femoral,popliteal, and foot pulses were equally diminished Carotid pulses:normal, no bruits

Investigations Hematocrit: 44% White blood cell count: 8 300/mm3.Erythrocyte sedimentation rate: 34 Electrocardiogram: sinus rhythmwith normal intervals and axis; a normal tracing Echocardiography: 5

cm × 5 cm mobile mass within the left atrium (see Figure 13.15) Itappears pedunculated and attached to the mid-portion of the atrial

septum During diastole, the mass prolapses into the mitral valve orificewith partial obstruction of left ventricular inflow.

Questions

1 What is the differential diagnosis of the echocardiographic lesion?

2 Is this likely to be a benign or malignant lesion?

3 What complications may arise from this process?

4 What therapy is indicated?

Answers

Answer to question 1 This young man presents with recent onset ofconstitutional symptoms, positional light-headedness, and a largemass within the left atrium that appears pedunculated Thedifferential diagnosis of this lesion includes a large thrombus, anintracardiac tumor or possibly infective endocarditis Any of theseconditions may present with the described constitutional symptoms.There is no apparent clinical reason for this individual to have anintracardiac thrombus Notably, the left atrium is not significantlyenlarged, and he does not have mitral valve disease or atrialfibrillation The pedunculated mass appears to be attached to theinteratrial septum, which is the most typical position for a left atrialmyxoma Conversely, thrombus within the left atrium is mostcommonly observed in the region of the atrial appendage Bloodcultures had been obtained but were negative, ruling againstendocarditis

Answer to question 2 Of the heart tumors, the location,pedunculated attachment, and origin at the mid-intra-atrial septum

in this case are most consistent with a cardiac myxoma, as describedbelow Myxomas are usually pathologically benign and are surgicallycurable

Answer to question 3 The clinical presentation of left atrial myxomaincludes constitutional symptoms (fever, chills, sweats, fatigue,myalgias), systemic emboli including stroke, and obstruction inintracardiac blood flow In this young man’s case, sudden changes inposition resulted in syncope due to obstruction of diastolic blood flowacross the mitral valve into the left ventricle

Answer to question 4 The presence of a left atrial myxoma withevidence of obstructed blood flow or embolization is a medicalemergency, and prompt surgical excision should follow

Further reading

Diseases of the pericardium

Cameron J, Oesterle SN, Baldwin JC, Hancock EW The etiology spectrum of

constrictive pericarditis Am Heart J 1987;113:354–60.

Fowler NO The pericardium in health and disease New York: Futura Publishing Co, 1985.

Klein AL, Cohen GI Doppler echocardiographic assessment of constrictive pericarditis,

cardiac amyloidosis, and cardiac tamponade Cleve Clin J Med 1992;59:278–90.

Lilly LS, ed Pathophysiology of heart disease Philadelphia: Lea & Febiger, 2002.

Oh JK, Hatle LK, Seward JB, et al Diagnostic role of Doppler echocardiography in

constrictive pericarditis J Am Coll Cardiol 1994;23:154–62.

Shabetai R, ed Diseases of the pericardium Cardiol Clin 1990;8:579–716.

Singh S, Wann LS, Schuchard GH, et al Right ventricular and right atrial collapse in

patients with cardiac tamponade: a combined echocardiographic and hemodynamic

study Circulation 1984;70:966.

Soulen RL, Stark DD, Higgins CB Magnetic resonance imaging of constrictive

pericardial disease Am J Cardiol 1985;55:480.

Spodick DH Macrophysiology, microphysiology, and anatomy of the pericardium: a

synopsis Am Heart J 1992;124:1046–51.

Diseases of the aorta

Belkin M, Donaldson MC, Whittemore AD Abdominal aortic aneurysms Curr Opin

Cardiol 1994;9:581–90.

Cigarroa JE, Isselbacher EM, DeSanctis RW, Eagle KA Diagnostic imaging in the

evaluation of suspected aortic dissection: old standards and new directions N Engl J

Med 1993;328:35–43.

Ernst CB Abdominal aortic aneurysm N Engl J Med 1993;328:1167–72.

Hagan PG, Nienaber CA, Isselbacher EM, et al The International Registry of Acute

Aortic Dissection (IRAD) JAMA 2000;283:897–903.

Izzo JL, Black HR, ed Hypertension primer: the essentials of high blood pressure Dallas:

American Heart Association, 1993.

Kouchokos NT, Daigenis D Surgery of the thoracic aorta N Engl J Med

Reynen K Cardiac myxomas N Engl J Med 1995;333:1610–17.

Fyke FE III, Seward JB, Edwards WD, et al Primary cardiac tumors: experience with

30 consecutive patients since the introduction of two-dimensional

echocardiography J Am Coll Cardiol 1985;5:1465–73.

Reeder, GS, Khandheria BK, Seward JB, et al Transesophageal echocardiography and

cardiac masses Mayo Clin Proc 1991;66:1101–9.

Salcedo EE, Cohen GI, White, RD, Davison MB Cardiac tumors: diagnosis and

management Curr Probl Cardiol 1992;17:73–137.

pulmonary hypertension

SAMUEL Z GOLDHABER

Pulmonary embolism and deep venous thrombosis (DVT) result inhundreds of thousands of hospitalizations, and attempts at promptdiagnosis and appropriate treatment of this illness cost billions ofdollars annually The incidence of pulmonary embolism and DVTincreases steadily with age For patients with pulmonary embolism,the most dangerous period precedes ascertainment of the correctdiagnosis The latter is quite difficult despite the availability oftraditional tests such as lung scanning, right heart catheterization, andpulmonary angiography, as well as plasma D-dimer enzyme linkedimmunosorbent assay (a blood screening test), leg ultrasonographywith color Doppler imaging (to detect venous thrombosis), chestcomputed tomography scanning, and echocardiography

Contemporary diagnosis of pulmonary embolism emphasizes astrategy that integrates clinical findings with a variety of diagnosticmodalities.1–4

The optimal approach to treatment (primary therapy withthrombolysis or embolectomy versus secondary prevention withanticoagulation alone) is somewhat controversial Risk stratificationhas emerged as the key concept in planning the treatment of patientswith pulmonary embolism Because pulmonary embolism is difficult

to diagnose, expensive to treat, and occasionally lethal despitetherapy, utilization of primary preventive measures is extraordinarilyimportant.5 Fortunately, a variety of effective mechanical measuresand pharmacologic agents can be employed Primary prophylaxis

is cost effective For every 1 000 000 patients undergoing operationwho receive primary prophylaxis against DVT and pulmonaryembolism, approximately US$60 000 000 can be saved in directhealthcare costs

Pathophysiology

The most spectacular advance in the molecular medicine of venousthrombosis is the discovery of a specific genetic mutation, termedfactor V Leiden, which predisposes to pulmonary embolism and DVT.This mutation results from a single nucleotide substitution of adeninefor guanine 1691, which replaces the amino acid arginine with

glutamine at position 506 This change eliminates the protein Ccleavage site in factor V Consequently, resistance to activated protein

C (aPC) is the phenotypic expression of this genetic mutation.Normally, one can add a specified amount of aPC to plasma andobserve prolongation in the activated partial thromboplastin time.However, patients with “aPC resistance” have an inadequateprolongation in partial thromboplastin time In contrast to classiccoagulation protein deficiencies, which are rare (such as antithrombinIII, protein C, and protein S), aPC resistance occurs frequently amongpatients with venous thrombosis

The allelic frequency of the factor V Leiden mutation is about 3%

in healthy American male physicians In the Physicians’ Health Study,the prevalence of the factor V mutation was three times higher amongmen who developed venous thrombosis.6

The ramifications of testing for factor V Leiden are far reaching Forexample, in a case–control study of premenopausal women whodeveloped DVT, the risk for thrombosis among users of oralcontraceptives was increased fourfold However, the risk forthrombosis among carriers of the factor V Leiden mutation waseightfold as compared with non-carriers When the risks associatedwith oral contraceptive use and factor V Leiden were combined, therate of thrombosis increased more than 30-fold

A careful family history is the most rapid and cost effective method

to identify a genetic predisposition to venous thrombosis

Conditions that increase venous stasis or cause endothelial damageare likely to predispose to venous thrombosis, especially amongpatients who already have subclinical hypercoagulable states Theseconditions include surgery, immobilization, trauma, obesity,increasing age, oral contraceptives, pregnancy, cancer (particularlyoccult adenocarcinoma), stroke, spinal cord injury, and indwellingcentral venous catheters Of course, patients who have had a priorpulmonary embolism or DVT are particularly susceptible torecurrences, even many years after the initial event

Most pulmonary emboli result from thrombi that originate in thepelvic or deep veins of the leg, and occasionally thrombi in theaxillary or subclavian veins embolize to the pulmonary arteries.Almost half of patients with proximal leg DVT have asymptomaticpulmonary emboli When venous thrombi become dislodged fromtheir sites of formation, they flow through the venous system to thepulmonary arterial circulation Although extremely large emboli maylodge at the bifurcation of the pulmonary artery, forming a “saddleembolus”, more commonly a second, third, or fourth orderpulmonary vessel is affected

Pulmonary embolism can have the following pathophysiologiceffects:

• increased pulmonary vascular resistance due to vascular obstruction,neurohumoral agents, or pulmonary artery baroreceptors

• impaired gas exchange due to increased alveolar dead space fromvascular obstruction and hypoxemia from alveolar hypoventilation,low ventilation/perfusion units, and right to left shunting, as well asimpaired carbon monoxide transfer due to loss of gas exchangesurface

• alveolar hyperventilation due to reflex stimulation of irritantreceptors

• increased airway resistance due to bronchoconstriction

• decreased pulmonary compliance due to lung edema, lunghemorrhage, and loss of surfactant

Right heart failure

The hemodynamic response to pulmonary embolism depends onthe size of the embolus, coexistent cardiopulmonary disease, andneurohumoral activation Pulmonary artery obstruction andcirculating neurohumoral substances reduce the pulmonary vascularbed and cause an increase in right ventricular afterload As rightventricular and pulmonary artery pressures rise, the right ventricledilates, becomes hypokinetic, and ultimately fails Progressive rightheart failure leads to reduced forward cardiac output and is usuallythe cause of death from acute pulmonary embolism

Sudden increases in right ventricular pressure adversely affect leftventricular function because of the anatomic juxtaposition of the twoventricles and “ventricular interdependence” Moderate right ventricularhypertension can displace the interventricular septum toward the leftventricle, resulting in decreased left ventricular diastolic filling andend-diastolic volume (Figure 14.1).7 The subsequent reduction incoronary artery perfusion pressure to the overloaded right ventricle maycause progressive right ventricular ischemia and failure Ultimately, rightventricular infarction, circulatory arrest, and death may ensue

Diagnosis

The differential diagnosis of pulmonary embolism is broad andcovers a spectrum from life-threatening disease such as acutemyocardial infarction to innocuous anxiety states (Box 14.1) Somepatients have concomitant pulmonary embolism and other illnesses.Thus, for example, if pneumonia or heart failure do not respond toappropriate therapy, then the possibility of coexisting pulmonaryembolism should be considered

Box 14.1 Differential diagnosis of pulmonary embolism

Anxiety; hyper ventilation syndrome

Paradoxic embolism may present with a sudden, devastating strokeand concomitant pulmonary embolism Such patients often have apatent foramen ovale evident on echocardiography Among patientssuspected of paradoxic embolism, occult leg vein thrombosis isfrequently present and often is confined to the calves

Non-thrombotic pulmonary embolism is less common thanthrombotic pulmonary embolism Fat embolism syndrome is mostoften observed after blunt trauma complicated by long bone fractures.Among cancer patients, tumor embolism is more difficult to diagnoseclinically than thrombotic pulmonary embolism because presenting

Figure 14.1 Parasternal shor t axis views of the right ventricle (RV) and left ventricle (LV) in (a) diastole and (b) systole There is diastolic and systolic bowing of the inter ventricular septum (arrows) into the left ventricle compatible with right ventricular volume and pressure overloads, respectively The right ventricle is appreciably dilated and markedly hypokinetic, with little change in apparent right ventricular area from diastole to systole PE, small pericardial effusion Reprinted with permission from Come 7

symptoms and signs are similar in both conditions Air embolus canoccur during placement or removal of a central venous catheter.8

Intravenous drug abusers may inadvertently inject a variety ofsubstances that contaminate their drug supply, such as hair, talc, andcotton These patients are also susceptible to septic pulmonaryembolus, which may be accompanied by endocarditis of the tricuspid

or pulmonic valves

Distinguishing between pulmonary embolism and primarypulmonary hypertension requires special consideration (Table 14.1).Primary pulmonary hypertension is a disease of unclear etiology inwhich the pulmonary vasculature undergoes extensive remodeling,leading to elevations in pulmonary artery pressure and pulmonaryvascular resistance The sustained increases in right ventricular

Table 14.1 Primary pulmonary hypertension versus recurrent pulmonary embolism

Recurrent pulmonary

Similarities

Symptoms Fatigue, dyspnea on exer tion (most

common); chest pain; syncope, hemoptysis, cyanosis (also common) Clinical course Progressive dyspnea, right hear t failure

Hemodynamics Elevated right hear t pressures, normal

pulmonar y capillar y wedge pressure Histology Thrombotic lesions usually present

per fusion defects per fusion defects Pulmonar y ar ter y systolic >60 <60

pressure (mmHg)

Pulmonar y angiogram “Pruning” Intraluminal filling defects Confounding problems Thrombi may occur on “Pruning” can also with angiogram or distal to PPH lesions suggest pulmonar y

embolism Diagnostic modalities Lung biopsy Pulmonar y angioscopy;

chest computed tomography or pulmonar y angiography

high dose nifedipine vena cava interruption;

or diltiazem; long-term thromboendar terectomy continuous intravenous

prostacyclin; bosentan PPH, primar y pulmonar y hyper tension

afterload result initially in right ventricular hypertrophy andsubsequently in right heart dilatation and depressed cardiac function.Both primary pulmonary hypertension and thrombotic pulmonaryembolism are treated with anticoagulants However, the prognosiswith primary pulmonary hypertension is usually more ominous.

In considering the diagnosis of thrombotic pulmonary embolism,clinical clues remain of paramount importance Unexplaineddyspnea, light-headedness, and chest pain are three of the mostcommon presenting symptoms of hemodynamically importantpulmonary embolism Whereas dyspnea, syncope, or cyanosisportends a major life-threatening pulmonary embolism, pleuriticchest pain often signifies that the embolism is small and located inthe distal pulmonary arterial system, near the pleural lining

Pulmonary embolism should be suspected in hypotensive patients

in the following circumstances9:

• there is evidence of or there are predisposing factors for venousthrombosis, and

• there is clinical evidence of acute cor pulmonale (acute rightventricular failure) such as distended neck veins, a third heartsound (S3) gallop, or a parasternal lift due to right ventricularpressure overload, tachycardia, or tachypnea, and especially if

• there is electrocardiographic evidence of acute cor pulmonalemanifested by a new S1-Q3-T3pattern, new incomplete right bundlebranch block, or right ventricular ischemia

Patients with massive pulmonary embolism present with systemicarterial hypotension and usually have anatomically widespreadthromboembolism Primary therapy with thrombolysis orembolectomy offers the greatest chance of survival.10 A moderate tolarge pulmonary embolus may be associated with right ventricularhypokinesis seen on echocardiography despite normal systemicarterial pressure There is increasing evidence that such patients maybenefit from primary therapy with thrombolysis or embolectomy (inaddition to secondary prevention with anticoagulation) in order toavert recurrent embolism Small to moderate pulmonary emboli areusually found in the presence of both normal right heart functionand normal systemic arterial pressure These patients have a goodprognosis with secondary prevention measures, such as eitheradequate anticoagulation or an inferior vena cava filter Pulmonaryinfarction is often accompanied by severe pleuritic chest pain and,rarely, by a small amount of hemoptysis Despite the discomfortusually experienced, the associated pulmonary embolus is almostalways anatomically small and hemodynamically inconsequential

Venous thrombosis as a surrogate

for pulmonary embolism

The presence of confirmed DVT is usually an adequate surrogate forpulmonary embolism Therefore, symptoms and signs of DVT shouldalso be sought when investigating the possibility of pulmonaryembolism DVT may be described as an intermittent “pulling”sensation at the insertion of the lower calf muscle into the posteriorportion of the lower leg An insidious feeling of calf cramping maysubsequently become more pronounced, and warmth, swelling, orerythema may ensue Eventually, the discomfort and abnormal physicalfindings may extend proximally into the popliteal fossa or thigh.Occasionally, a cord may be palpable, or prominent venous collateralsmay appear However, Homans’ sign, defined as increased resistance orpain during dorsiflexion of the foot, is unreliable and non-specific

In patients with prior DVT, the sudden onset of diffuse leg swellingusually indicates venous insufficiency and not recurrent venousthrombosis Other clues to venous insufficiency include brownishpigmentation (and rarely ulceration) of the medial malleolus, or pain,cramping, or calf mottling and discoloration when standing

Laboratory and imaging tests

Classic chest radiograph findings include focal oligemia(Westermark’s sign), indicating massive central embolic occlusion, or

a peripheral wedge shaped density above the diaphragm (Hampton’shump), indicating pulmonary infarction Enlargement of a centralpulmonary artery, especially with progressive expansion on serialradiographs, is a cardinal sign of pulmonary hypertension on plainchest radiography

Enlargement of the right descending pulmonary artery (Palla’s sign)

to greater than 16 mm diameter also suggests pulmonary arterialhypertension Chest radiography can also help identify patients withother diseases, such as lobar pneumonia or pneumothorax, which canmimic pulmonary embolism However, patients with these illnessescan also have concomitant pulmonary embolism

The electrocardiogram is useful not only to help exclude acutemyocardial infarction but also because patients with a largepulmonary embolism may have electrocardiographic manifestations

of right heart strain (Box 14.2).9 The differential diagnosis of newright heart strain includes acute pulmonary embolism, acute asthma,

or exacerbation of chronic bronchitis in patients with chronicobstructive pulmonary disease

Box 14.2 Electrocardiographic findings in pulmonary embolism9

Incomplete or complete right bundle branch block

S in leads I and aVL >1·5 mm

Transition zone shift to V5

QS in leads III and aVF, but not in lead II

QRS axis >90° or indeterminate axis

Low limb lead voltage

T-wave inversion in leads III and aVF or in leads V1–V4

Unfortunately, the time honored screening test of abnormal roomair arterial blood gases is not useful in triaging patients suspected ofhaving pulmonary embolism.11 Although arterial blood gases areinexpensive and readily available, extensive analyses of the largeProspective Investigation of Pulmonary Embolism Diagnosis(PIOPED) database12 indicate that even sophisticated calculations ofthe alveolar–arterial oxygen difference do not accurately separatepatients with pulmonary embolism from those without pulmonaryembolism Therefore, arterial blood gases should not be obtained as ascreening test in patients with suspected pulmonary embolism.The most promising blood test for pulmonary embolism is anabnormally elevated level of enzyme linked immunosorbent assay(ELISA) determined plasma D-dimer (>500 ng/ml), which has a morethan 90% sensitivity for identifying patients with pulmonaryembolism proven by lung scan or by angiogram.13,14This test relies onthe principle that most patients with pulmonary embolism haveongoing endogenous fibrinolysis that is not effective enough toprevent pulmonary embolism but that does break down some of thefibrin clot to D-dimers (Figures 14.2 and 14.315) These D-dimers can

be assayed by monoclonal antibodies that are commercially available.Although elevated plasma concentrations of D-dimers are sensitive forthe presence of pulmonary embolism, they are not specific Levels areelevated in patients for at least 1 week postoperatively and are alsoincreased in patients with myocardial infarction, sepsis, or almost anyother systemic illness Therefore, the plasma D-dimer ELISA is bestutilized when suspected pulmonary embolism patients have nocoexisting acute systemic illness The usual D-dimer measurementobtained in hospital laboratories employs a latex agglutination assay

to detect disseminated intravascular coagulation Unlike the ELISA,the latex agglutination assay is simply not sensitive enough forreliable pulmonary embolism screening.14Therefore, use of an ELISAbased assay is necessary to “rule out pulmonary embolism”

Ventilation/perfusion lung scanning is the principal diagnosticimaging test for suspected acute pulmonary embolism (Table 14.2).Small particulate aggregates of albumin or microspheres labeled

D-dimers (XDP)

with a γ emitting radionuclide (usually technetium) are injectedintravenously and are trapped in the pulmonary capillary bed Aperfusion scan defect suggests decreased blood flow, possibly due topulmonary embolism Ventilation scans, obtained with radiolabeledinhaled gases such as xenon or krypton, may improve the specificity

of the perfusion scan Abnormal ventilation scans indicate ventilated lung, thereby providing possible explanations for perfusiondefects other than acute pulmonary embolism The ventilation/perfusion scan is most useful if it is normal or if it demonstrates apattern that is suggestive of a high probability of pulmonaryembolism The diagnosis of pulmonary embolism is very unlikely(<5% chance) in patients with normal and near normal scans; incontrast, it is about 90% certain in patients with high probabilityscans A high probability scan for pulmonary embolism is defined ashaving two or more segmental perfusion defects in the presence ofnormal ventilation Unfortunately, fewer than half of patientswith angiographically confirmed pulmonary embolism have a highprobability scan Intermediate probability scans or low probabilityscans with high clinical suspicion do not exclude pulmonaryembolism.15 In PIOPED, 40% of patients with high clinical suspicion

non-for pulmonary embolism and “low probability” scans did, in fact,have pulmonary embolism at angiography (Table 14.2).

Ultrasonography of the leg veins is usually accurate in diagnosingproximal leg DVT in symptomatic outpatients but it is an insensitivescreening test for DVT in asymptomatic inpatients.16 Overall, aboutone-third of pulmonary embolism patients have no venographicevidence of leg DVT Therefore, if clinical suspicion of pulmonaryembolism is high, then the diagnosis of pulmonary embolism should

be pursued even in the absence of DVT

Bedside echocardiography is particularly useful among clinicallyunstable patients who seem “too ill” to undergo lung scanning orpulmonary angiography If transthoracic echocardiographic imagesare technically inadequate, then transesophageal echocardiographyshould be considered Although it is unusual for echocardiography

to demonstrate a thrombus in the main pulmonary artery or at itsproximal bifurcation, a constellation of indirect findings will oftensuggest pulmonary embolism (Box 14.3) However, patients can alsohave a normal echocardiogram despite anatomically extensive

pulmonary embolism Echocardiography for suspected pulmonaryembolism can also help to exclude other life-threatening conditions,such as ventricular septal rupture, aortic dissection, and pericardialtamponade The distinction is important because patients with thesealternative, grave illnesses require urgent therapy that differs radicallyfrom that for pulmonary embolism.

Box 14.3 Echocardiographic findings in pulmonary embolism

Right ventricular dilatation

Right ventricular hypokinesis (especially the right ventricular free wall)

Bowing of the inter ventricular septum into the left ventricle

Extrinsic compression of an intrinsically normal left ventricle

Tricuspid regurgitation

Pulmonar y ar ter y dilatation

Decreased inspirator y collapse of inferior vena cava

Right heart catheterization and pulmonary angiography

Before undertaking diagnostic pulmonary angiography, accurateand high quality recordings of right heart pressures and waveformsshould be obtained A carefully performed right heart catheterizationmay provide important clues to alternative diagnoses such as cardiactamponade and left ventricular failure Patients with dyspnea andpulmonary hypertension might have intracardiac shunting, whichcan be defined most precisely by an oxygen saturation run If thepressure tracing “dampens” or “wedges” in the proximal pulmonaryartery without balloon expansion, then anatomically massivepulmonary embolism should be suspected before injection of contrastagent Even when the angiographic diagnosis is in fact pulmonaryembolism, a carefully performed right heart catheterization can

Table 14.2 PIOPED: pulmonary embolism status

provide clues about the age of the thrombus, based on the degree ofelevation of the pulmonary artery systolic pressure In general, if thepulmonary artery systolic pressure exceeds approximately 50 mmHg,then the differential diagnosis should include chronic pulmonaryembolism and acute pulmonary embolism superimposed on chronicpulmonary embolism.

Pulmonary angiography can almost always be accomplished safely if:

• selective angiography is performed, with the perfusion lung scanserving as a road map to the angiographer

• soft, flexible catheters with side holes are employed, rather thanstiff catheters with end holes

• a low osmolar contrast agent is utilized to minimize the transienthypotension, heat, and coughing sensation that often occurs withconventional radiocontrast agents

Among patients undergoing pulmonary angiography, anintraluminal filling defect seen in more than one projection is themost reliable feature to diagnose pulmonary embolism Standardcontrast pulmonary angiography can detect emboli accurately inperipheral vessels as small as 1–2 mm Secondary signs of pulmonaryembolism reflect decreased perfusion and consist of abrupt occlusion(“cut-off”) of vessels, oligemia or avascularity of a segment, aprolonged arterial phase with slow filling and emptying of veins, andtortuous tapering peripheral vessels

Pulmonary angiography may also help diagnose chronic pulmonaryembolism Arteries may appear “pouched”, and thrombus appearsorganized with a concave edge Band-like defects called webs may bepresent, in addition to intimal irregularities and abrupt narrowing orocclusion of lobar vessels

With increasing frequency, chest computed tomography scanningwith contrast is replacing classical contrast pulmonary angiography,which is now being reserved for patients who have equivocal chestcomputed tomography scans or who require therapeutic proceduressuch as catheter embolectomy in the interventional laboratory

Overall diagnostic strategy

An integrated diagnostic approach is advocated, which combinesclinical assessment, lung scanning, and evaluation for DVT This strategynarrows the number of patients who require pulmonary angiography.Often, a definitive diagnosis can be obtained by combining clinicallikelihood, plasma D-dimer ELISA, leg ultrasonography, lung scan, and

chest computed tomography scan results When the plasma D-dimerELISA is elevated in the presence of a normal leg ultrasound, normalechocardiogram, and non-diagnostic lung scan and chest computedtomography scan, the clinical setting may warrant pulmonaryangiography (Figure 14.4) Ordinarily, pulmonary angiography isunnecessary for patients with high probability lung scans, even ifthrombolysis is planned This strategy is analogous to the widelyaccepted practice of empirically administering thrombolysis to patientswith chest pain and ST-segment elevation on electrocardiogram whohave suspected (but not definitely proven) acute myocardial infarction,rather than proceeding with diagnostic coronary angiography.

Suspect PE Pulmonary embolus diagnosis strategy

Normal

Stop workup

Pulmonary angiogram

We consider patients with pulmonary embolism to behemodynamically unstable if they have right ventricular hypokinesis,usually documented on echocardiogram, even in the presence of anormal systemic arterial pressure.15–17 Such patients may initiallyappear deceptively stable based on the clinical evaluation alone Weuse echocardiographic assessment of right ventricular function tohelp risk stratify pulmonary embolism patients into good prognosis(Figure 14.5) or ominous prognosis (Figure 14.6) groups Pulmonaryembolism patients with good prognosis do well clinically withanticoagulation alone or filter placement (secondary prevention).Pulmonary embolism patients with ominous prognosis may havebetter outcomes if primary therapy is utilized (i.e thrombolysis orembolectomy) in addition to anticoagulation

Despite adequate heparin anticoagulation, patients with rightventricular hypokinesis are at high risk for recurrent pulmonaryembolism and clinical deterioration, even if they are normotensiveinitially.1Therefore, they are potential candidates for primary therapywith thrombolysis or mechanical intervention If patients arecandidates for thrombolysis, then we administer thrombolysis in

Risk stratify:

good prognosis

Normotension plus normal RV

Secondary prevention

is adequate

Consider anticoagulation

alone

Insert IVC filter Figure 14.5 Risk stratification: pulmonar y embolism patients with good prognosis have good outcomes with secondar y prevention alone

preference to embolectomy, which is reserved for those few instances

in which thrombolysis fails or for situations in which thrombolysis iscontraindicated Dobutamine – a β-adrenergic agonist with positiveinotropic and pulmonary vasodilating effects – should be utilized totreat right heart failure and cardiogenic shock In general, volumeloading is ill advised because increased right ventricular dilatation canlead to even further reductions in left ventricular forward output

Anticoagulation

Unfractionated heparin is administered immediately, as soon aspulmonary embolism is suspected clinically Initiate heparin with abolus of 5000–10 000 units followed by a continuous intravenousinfusion of approximately 1250 units/hour while the diagnostic work

up is pursued The partial thromboplastin time should then be adjusted

to a target of at least twice the control value In established pulmonaryembolism, failure to use heparin in adequate doses can prolong theduration of hospital stay, predispose to recurrent pulmonary embolism,and increase the costs of medical care Low molecular weight heparin is

Risk stratify:

ominous prognosis

Hypotension, or

RV hypokinesis

Consider primary therapy

Anticoagulation

plus thrombolysis

Embolectomy:

catheter/

surgical Figure 14.6 Risk stratification: pulmonar y embolism patients with ominous prognosis may have improved outcomes if primar y therapy (thrombolysis or embolectomy) is utilized in addition to anticoagulation

evolving as a contemporary alternative to unfractionated heparin formanagement of acute pulmonary embolism

Bleeding and thrombocytopenia are the major side effects of term unfractionated heparin administration When unfractionatedheparin is administered chronically (the usual case when pulmonaryembolism is being treated during pregnancy), heparin associatedosteopenia may develop Oral anticoagulation with warfarin can bestarted as soon as the partial thromboplastin time is within thetherapeutic range Patients should receive at least 5 days of heparinwhile an adequate level of oral anticoagulation is established Theprothrombin time, utilized to adjust the dose of oral anticoagulation,should be reported according to the well standardized InternationalNormalized Ratio (INR) but not according to the prothrombin time ratio

short-or the prothrombin time expressed in seconds The target INR range is2·0–3·0 However, for patients with pulmonary embolism andantiphospholipid antibodies, more intensive anticoagulation, with atarget INR range of 3·0–4·0, will result in fewer recurrent embolic events.After discontinuation of anticoagulation, the risk for recurrentpulmonary embolism is surprisingly high Patients with underlyingcancer that is not cured or massive obesity should probably beanticoagulated indefinitely For other patients, I anticoagulate thefirst episode of isolated calf vein thrombosis for 3 months, andproximal DVT or pulmonary embolism for 6 months

Inferior vena cava filter

An inferior vena caval filter does not directly treat an establishedpulmonary embolism16 but it does provide secondary prevention ofrecurrent pulmonary embolism Accepted indications for filter insertioninclude established venous thrombosis with active, clinically importantbleeding that prohibits the use of heparin; and recurrent pulmonaryembolism despite adequate anticoagulation An inferior vena cava filtermay also be used adjunctively to prevent recurrent pulmonary embolismamong hemodynamically compromised pulmonary embolism patientswho cannot be treated with thrombolytic therapy Whenever possible,anticoagulation should also be utilized to prevent further thrombosis

Thombolysis

Thrombolysis (Box 14.4)10,17 and mechanical catheterinterventions18 debulk clot and provide primary treatment ofpulmonary embolism Over the past decade, the administration ofthrombolysis to pulmonary embolism patients has been streamlined

so that it is safer, less expensive, and less time consuming (Table 14.3)

Box 14.4 US Food and Drug Administration approved thrombolyticregimens for pulmonary embolism

Streptokinase (approved in 1977): 250 000 IU as a loading dose over 30 min, followed by 100 000 U/hour for 24 hours

Urokinase (approved in 1978): 2000 IU/lb as a loading dose over 10 min, followed by 2000 IU/lb per hour for 12–24 hours

Recombinant tissue-type plasminogen activator (approved in 1990): 100 mg

as a continuous peripheral intravenous infusion administered over 2 hours

Contraindications to thrombolysis include intracranial disease,recent surgery, or trauma There is about a 1% risk for intracranialhemorrhage Careful patient screening for potential contraindications

is the best way to minimize bleeding risk

Embolectomy

There has been a resurgence of interest in aggressive interventionalmanagement of pulmonary embolism, often undertaken in the cardiaccatheterization laboratory.18,19 The Greenfield embolectomy device isprobably the most frequently used catheter based method of extractingTable 14.3 Old and new concepts in pulmonary embolism thrombolysis

Concept

Diagnosis Mandator y pulmonar y High probability lung scan,

angiogram suggestive echocardiogram

(if hypotensive), or chest computed tomography scan with contrast

Indications Systemic ar terial Hypotension or normotension

hypotension with accompanying right

ventricular hypokinesis Time window 5 days or less 14 days or less

Agents Streptokinase or r t-PA

urokinase Dosing regimens 24 h streptokinase or 100 mg/2 h r t-PA

12–24 h urokinase Route Via pulmonar y ar ter y Via peripheral vein

catheter Coagulation tests “DIC screens” ever y PTT at conclusion of

4–6 h during infusion thrombolysis DIC, disseminated intravascular coagulation; PTT, par tial thromboplastin time;

r t-PA, recombinant tissue-type plasminogen activator

pulmonary arterial thrombus It consists of a 10 F steerable catheterwith a suction cup attached at the tip Because of the cup’s large size,

a surgical venotomy is utilized, usually in the right internal jugularvein A steerable handle controls progression of the catheter throughthe right cardiac chambers and the pulmonary arterial branches Ifcatheter based strategies fail, then emergent surgical embolectomywith cardiopulmonary bypass can be undertaken.20A non-randomizedcomparison of recombinant tissue-type plasminogen activatorthrombolysis versus surgical embolectomy indicated that bothapproaches can be lifesaving in the majority of patients with massivepulmonary embolism It is best to refer patients for embolectomybefore the development of overt cardiogenic shock

Pulmonary thromboendarterectomy

Patients with chronic pulmonary hypertension due to priorpulmonary embolism may be virtually bedridden with breathlessnessbecause of high pulmonary arterial pressures They should be consideredfor pulmonary thromboendarterectomy which, if successful, can reduceand at times even cure pulmonary hypertension The operation involves

a median sternotomy, institution of cardiopulmonary bypass, and deephypothermia with circulatory arrest periods Incisions are made in bothpulmonary arteries The surgeon performing thromboendarterectomycreates an endarterectomy plane and then dissects endothelializedthrombus from as many involved pulmonary vessels as possible Atselected centers, pulmonary thromboendarterectomy can be performedwith good results and at an acceptable risk among patients debilitatedfrom chronic pulmonary hypertension due to pulmonary embolism

Primary prevention

Primary prophylaxis is of paramount importance becausepulmonary embolism is both difficult to recognize and expensive totreat Fortunately, mechanical and pharmacologic prophylaxismodalities are widely available and usually effective (Table 14.4)

Case studies

Case 14.1

A 21-year-old woman, who was 8 weeks pregnant and nulliparous,was hospitalized with suspicion of pulmonary embolism She had

complained of pleuritic chest and back discomfort for 1 week Herprimary care provider estimated the overall likelihood of pulmonaryembolism to be 50% She was previously healthy A “cold” (viralsyndrome) was going around the family.

Examination Physical examination: the patient appeared tearful

and anxious No abnormalities of skin, nail beds, or oral mucosa.Pulse: 88 beats/min Blood pressure: 105/65 mmHg in right arm.Respiratory rate: 24/min Jugular venous pulse: 8 cm Cardiacimpulse: normal First heart sound: normal Second heart sound: splitnormally on inspiration No added sounds or murmurs Chestexamination: normal air entry, no rales or rhonchi Abdominalexamination: soft abdomen, no tenderness, and no masses Normal

Table 14.4 Primary prevention of pulmonary embolism

Gynecologic cancer surger y Coumadin (target INR 2·0–2·5) ± IPC

Unfractionated heparin 5000 U ever y 8 h

± IPC or enoxaparin 40 mg/day or dalteparin 5000 units/day Urologic surger y War farin (target INR 2·0–2·5) ± IPC Thoracic surger y IPC plus unfractionated heparin

5000 U ever y 8 h High risk general surger y IPC or graded compression stockings plus (for example prior VTE, unfractionated heparin 5000 U ever y current cancer, or obesity) 8 h or enoxaparin 40 mg/day or

dalteparin 5000 units/day General, gynecologic, or urologic Graded compression stockings plus surger y (without prior VTE) for unfractionated heparin 5000 U ever y non-cancerous conditions 12 h or enoxaparin 40 mg/day or

dalteparin 2500 units/day IPC alone

Neurosurger y, eye surger y, or Graded compression stockings ± IPC other surger y when prophylactic

anticoagulation is contraindicated

Medical conditions Graded compression stockings ± heparin

5000 U ever y 8–12 h or enoxaparin

40 mg/day IPC alone INR, International Normalized Ratio; IPC, intermittent pneumatic compression; VTE, venous thromboembolism

liver span No peripheral edema Femoral, popliteal, posterior tibial,and dorsalis pedis pulses: all normal volume and equal Carotidpulses: normal, no bruits Optic fundi: normal.

Investigations Chest x ray and electrocardiogram: normal.

Ventilation/perfusion lung scan: intermediate probability forpulmonary embolism Leg ultrasound: negative for DVT.Echocardiogram: normal, including normal right ventricularfunction D-dimer: a plasma D-dimer enzyme linked immunosorbentassay (ELISA) was 2003 ng/ml (normal <500 ng/ml)

Questions

1 Based on the lung scan result and the primary care provider’sclinical impression, what is the PIOPED estimate of her likelihood

of having a pulmonary embolism?

2 What is the differential diagnosis?

3 How does the elevated plasma D-dimer ELISA affect your estimate

of the likelihood of pulmonary embolism?

4 How does the normal echocardiogram affect your estimate of thelikelihood of pulmonary embolism?

5 What is the “down side” of empiric treatment for pulmonaryembolism?

6 What are the possible advantages and disadvantages ofpulmonary angiography?

7 What do you think was actually done in this case, and what wasthe outcome?

Answers

Answer to question 1 With an intermediate clinical suspicion andintermediate probability lung scan, the PIOPED estimate of herlikelihood of pulmonary embolism is 28% (see Table 14.2)

Answer to question 2 The differential diagnosis includes acute viralillness, muscoloskeletal pain, pericarditis, and pulmonary embolism.Answer to question 3 The presence of a markedly elevated plasma D-dimer level means that the D-dimer cannot be used in this case toexclude pulmonary embolism If the clinical suspicion is sufficientlyhigh, then the work up for pulmonary embolism should continue or,alternatively, the patient should be treated empirically for pulmonaryembolism

Answer to question 4 The normal echocardiogram does not excludepulmonary embolism, but it does indicate that if pulmonary

embolism is present then the prognosis will be favorable withsecondary prevention alone (i.e anticoagulation) There will be noneed to consider thrombolytic therapy or embolectomy.

Answer to question 5 The “down side” of empiric treatment spans arange of medical, psychologic, and social considerations Medically, ifshe does not really have pulmonary embolism, then she would beexposed unnecessarily to heparin Although in her age group bleeding

is exceedingly rare, prolonged exposure to heparin places her at riskfor developing heparin associated osteopenia or thrombocytopenia.She and society would also incur the expense and inconvenience offull dose heparin during pregnancy, followed by warfarin postpartum.She would be instructed to avoid all forms of estrogen andprogesterone contraceptives, as well as postmenopausal hormonereplacement therapy Finally, she would be labeled as having suffered

a pulmonary embolism, without solid evidence to support thiscontention Because of the inherited nature of some pulmonaryemboli, she would always be concerned about whether her childrenwould be at risk for venous thrombosis

Answer to question 6 If chest computed tomography scan or classicpulmonary angiography were normal, then she could be dischargedwithin several hours of completing the procedure The fetal exposure

to radiation during pulmonary angiography is well below therecommended maximum for pregnancy

Answer to question 7 After considerable discussion, the patient andher primary care provider agreed to proceed with cardiaccatheterization and pulmonary angiography Appropriate leadshielding of the abdomen was employed, and fluoroscopy time waskept to a minimum Right heart pressures were entirely normal (rightatrial 5 mmHg, pulmonary artery 25/9 mmHg), but angiographydemonstrated a large right lower lobar pulmonary embolism(Figure 14.7) Therefore, she was maintained on continuousintravenous heparin for her entire pregnancy and was anticoagulatedwith warfarin postpartum Her delivery was entirely unremarkableand she was discharged home uneventfully

Case 14.2

A 53-year-old man presented with gradually worsening dyspnea onexertion He complained of fatigue and inability to work and pursueleisure activities without marked shortness of breath

At age 25 years he had suffered bilateral DVT of the legs but did notreceive a prolonged course of anticoagulation because of a duodenalulcer 3 years previously At age 36 years he presented with syncopeaccompanied by tachycardia and diaphoresis His electrocardiogram atthat time was notable for atrial fibrillation and inverted T waves inleads V1–V3 Five years later he complained of exertional dyspnea Alung scan demonstrated a high probability of pulmonary embolism Atthat time his mean pulmonary arterial pressure was 32 mmHg, and apulmonary angiogram was positive for pulmonary embolism He wasplaced on warfarin During the ensuing 12 years of anticoagulation, hisdyspnea worsened to the point where he could not pursue the activelifestyle that he desired.

Examination Physical examination: the patient appeared

normal No abnormalities of skin, nail beds, or oral mucosa Pulse:

94 beats/min, normal character, irregularly irregular Blood pressure:120/80 mmHg in right arm Jugular venous pulse: 10 cm Cardiac

Figure 14.7 Pulmonar y angiography with digital subtraction (left anterior oblique projection) demonstrates a large, acute embolus in the right lower lobar pulmonar y

ar ter y (arrowhead)

impulse: normal First heart sound: normal: Second heart sound: splitnormally on inspiration Gallop rhythm and grade 2/6 holosystolicmurmur heard at left lower sternal border, which increased withinspiration Chest examination: normal air entry, no rales or rhonchi.Abdominal examination: soft abdomen, no tenderness, and nomasses Normal liver span No peripheral edema Femoral, popliteal,posterior tibial, and dorsalis pedis pulses: all normal volume andequal Carotid pulses: normal, no bruits Optic fundi: normal.

Investigations Electrocardiogram: atrial fibrillation at a rate of

94/min; QRS axis of 116°; right axis deviation; right ventricularhypertrophy; left posterior fascicular block; diffuse ST and T waveabnormalities Echocardiogram: very enlarged and moderatelyhypertrophied right ventricle with moderately reduced systolicfunction; the left ventricle was relatively small with marked septalflattening and abnormal septal motion but preserved systolic function

Questions

1 What is the pathophysiology of this patient’s condition?

2 What risks are associated with various management strategies?

3 What further diagnostic tests might be considered?

4 What do you think was actually done in this case, and what wasthe outcome?

Dyspnea is associated with an increase in dead space ventilation,resulting in high minute ventilation demands and an inability ofcardiac output to meet metabolic demands

Findings on physical examination are influenced by the degree ofpulmonary hypertension and right ventricular dysfunction that ispresent This patient has evidence of tricuspid regurgitation and rightheart failure on physical examination This was corroborated by hiselectrocardiogram and echocardiogram

Answer to question 2 If treated medically he would continue toreceive warfarin and would be placed on round the clock oxygen Hisdyspnea and right ventricular failure would, nevertheless, inexorablyworsen With pulmonary thromboendarterectomy he would have an