Cardiology Core Curriculum A problem-based approach - part 6 pot

Thepresent discussion focuses on the types of congenital heart diseasethat may present for the first time in adulthood.1–4 Left to right shunts Atrial septal defects Atrial septal defect

at the flat portion of the Starling curve This may require a reduction

in the diuretic dose or even a “diuretic holiday” for 1 or 2 days inorder to introduce ACE inhibitors A slow upward titration will alsoincrease the likelihood that targeted doses will be reached

Adverse reactions include the development of an ACE induced cough; this is mediated by bradykinins, which are increasedwith ACE inhibition No specific therapy is effective in relievingcough Patients either cope with antitussives or discontinue therapy.Less frequently, development of angioneurotic edema, drugeruptions, and rarely drug-induced neutropenia occur ACE inhibitorsare contraindicated in pregnancy

inhibitor-Several points regarding ACE inhibitor therapy for heart failureshould be remembered

• ACE inhibitors are indicated in all patients with heart failure andleft ventricular systolic dysfunction

• Therapy should mimic that of the major survival trials in terms ofdose and agent selected

• ACE inhibitors should not be suspended or discontinued because ofhypotension unless the patient is symptomatic This is because ofthe interrelationship between blood pressure (BP), cardiac output(CO) and systemic vascular resistance (SVR), which is defined by BP

= CO × SVR Even though ACE inhibitors and other vasodilatorsdecrease SVR, the corresponding increase in CO offsets any drop in

BP unless the patient is volume depleted

Angiotensin II receptor antagonists

These agents competitively inhibit the receptors for angiotensin II,and there is a lack of associated cough because there is no effect onbradykinins The weight of evidence suggests that these agents should

be considered in patients being treated with digitalis, diuretics, and a

β-blocker who cannot tolerate an ACE inhibitor because of cough orangioedema.5

ββ -Blockers

Activation of the sympathetic nervous system adversely influences thecourse of chronic heart failure Until relatively recently, it was thoughtthat β-adrenoreceptor antagonists were contraindicated in heart failurebecause of their negative inotropic effects However, it has emerged thatseveral β-blockers (carvedilol,12 bisoprolol, and extended releasemetoprolol) improve mortality and quality of life, and reduce

hospitalization in patients with mild to moderate (New York HeartAssociation class II or III) heart failure.13 Initiation of this therapyrequires individualized drug dosing and very careful clinical monitoring.

Additional therapy for congestive heart failure

Electrolyte supplementation is frequently required in patients onsignificant diuretic doses Potassium supplementation is mostfrequently required but can cause gastrointestinal irritation The usualsupplemental dose required is 20–120 mEq/day (20–120 mmol/day)

If higher doses are required, then concomitant use of a sparing diuretic should be considered Hypokalemia may be difficult tocorrect without first correcting hypomagnesemia, because Mg2 + is acofactor for the Na+/K+-ATPase pump Magnesium supplementation isdifficult because serum measures do not accurately reflect magnesiumstores The oral supplements are poorly absorbed, which also makesrepletion difficult If renal function is normal, then the dose ofmagnesium is 14 mEq (14 mmol) three to four times daily

potassium-Anticoagulants are often given to patients with marked impairment

in systolic function, or dilated cardiomyopathy to protect against thedevelopment of formation of mural thrombus and possible systemicembolization, which may result in strokes or pulmonary emboli.14Certainly, anticoagulants should be given to patients at highest risk(i.e those with multiple risk factors for emboli [atrial fibrillation,mitral valve disease] or prior embolic events) Warfarin sodium is thepreferred agent and should be given to adjust the InternationalNormalized Ratio to 2·0

Amiodarone is a class III antiarrhythmic that has shown somepromise in small trials of heart failure patients It causes a slower heartrate and mild vasodilatation, and suppresses arrhythmias, but it doesnot reduce the incidence of sudden death or prolong survival.15Many patients with heart failure require care in a critical caresetting where parenteral agents are used The available agents includethe following:

• intravenous nitroglycerin, which causes preload reduction

• intravenous nitroprusside, which reduces afterload

• dobutamine, which stimulates cardiac contractility and increasescardiac output

• dopamine, which at low doses improves renal blood flow; atmoderate doses it stimulates cardiac contractility, and at higherdoses it causes systemic vasoconstriction and raises blood pressure

• milrinone, which causes vasodilatation and augmented cardiacoutput by inhibiting phosphodiesterase

Cardiac transplantation

Advances in candidate selection, surgical techniques, postoperativecare, immunosuppression, surveillance for rejection, and avoidance ofsevere infection has resulted in dramatic improvements in survivalsince the introduction of cardiac transplantation in 1968 One yearsurvival rates now average 80%, and in selected centers the 1 yearsurvival exceeds 90% Five year survival is approximately 70% Themajor limitation to cardiac transplantation is the availability of donororgans, and not every patient who can benefit from cardiactransplantation will receive a heart The task for transplantcommittees is to decide who are the best candidates for this limitedresource (Box 10.2)

Box 10.2 Heart transplantation

When to refer for transplantation?

Left ventricular ejection fraction <<0·20

Class IV congestive hear t failure

Intractable arrhythmias that are not amenable to other therapy

Refractor y ischemia despite effor ts at revascularization

Poor exercise capacity by objective criteria

Marked hyponatremia

Fluctuating renal/hepatic function

Contraindications

Severe comorbidities

Intrinsic renal, hepatic, or pulmonar y disease

Severe peripheral vascular disease

Insulin-dependent diabetes with end-organ complications

Recent stroke

Recent pulmonar y infarction

Active infection or malignancy

is an active, 20 pack-year smoker, with hypertension treated for

5 years with calcium channel blockers and hyperlipidemia Bloodpressure was 160/90 mmHg 3 months previously

Examination Physical examination: the patient appeared morbidly

obese (305 lb [138·6 kg]) Height: 68 inches (172·7 cm) Noabnormalities of skin, nail beds, or oral mucosa Pulse: 92 beats/min,normal character Blood pressure: 110/70 mmHg in right arm Jugularvenous pulse: normal Cardiac impulse: normal First heart sound:normal Second heart sound: split normally on inspiration Fourthheart sound present No murmurs Two component friction rubheard 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

Investigations Chest x ray: cardiomegaly with clear lung fields.

Electrocardiogram: 2 mm flat ST depression in leads I, aVL, V5, V6;T-wave inversions in leads V4–V6 Electrolytes: potassium 3·6 mEq/l(3·6 mmol/l); creatinine 1·9 mg/dl (168µmol/l); glucose 165 mg/dl(9·1 mmol/l) Serial cardiac enzymes: creatinine kinase-MB 79–96–54units (normal range 0–3) Echocardiogram: inferolateral hypokinesis;mild mitral regurgitation; left ventricular dimension 5·8 cm (normal

<5·5 cm); left ventricular septum 1·6 cm; left ventricular posteriorwall 1·5 cm (normal <1·1 cm); small pericardial effusion; leftventricular ejection fraction 0·27 Exercise stress test: the patientexercised for 12 min on a modified Bruce protocol to peak heart rate

140 beats/min, peak systolic blood pressure 190 mmHg, MET level 6·5(consistent with peak oxygen consumption of 23 ml/kg per min) Noanginal symptoms or ST-T changes on electrocardiogram duringexercise

Hospital day 5 The patient is ambulating and is asymptomatic, with

normal vital signs and cardiac examination, except for presence of afourth heart sound on auscultation

Questions

1 What diagnosis or diagnoses are applicable? (A) Congestive heartfailure (B) Pericarditis (C) Q-wave myocardial infarction (D) Non-Q-wave myocardial infarction (E) A and C (F) B and D (G) A, B, and C

2 Based on the diagnosis and clinical course, what would be the bestmedical regimen at the time of discharge? (A) The patient is notready for discharge; additional procedures need to be done.(B) Aspirin, lipid lowering therapy, and calcium channel blocker(nifedipine) (C) β-blocker (propanolol) (D) Aspirin, ACEinhibitor, β-blocker, and lipid lowering medication (E) Nomedical therapy is indicated

3 Which of the following findings confirm the diagnosis of CHF inthis case? (A) Left ventricular ejection fraction below 0·30

(B) Dilated left ventricle (C) History of hypertension (D) All ofthese (E) None of these.

4 Is this patient a candidate for eventual heart transplantation?(A) Yes – he has reduced left ventricular function with an ejectionfraction under 0·30 and reduced exercise capacity, with anestimated maximal oxygen consumption below 30 ml/kg per min.(B) No – his clinical course is inconsistent with the indications fortransplantation

Answers

Answer to question 1 F This patient has had a non-Q-wave myocardialinfarction complicated by pericarditis The electrocardiographicfindings rule out a Q-wave myocardial infarction The diagnosis of anacute myocardial infarction is confirmed by the diagnostic enzymepattern Pericarditis is confirmed by the presence of a pericardialfriction rub and a small pericardial effusion

The important concept arising from this question is that thediagnosis of CHF cannot be made on the basis of an abnormalmeasure of left ventricular function The left ventricular ejectionfraction is reduced and suggests a poor prognosis, but is not sufficientfor the diagnosis of CHF Remember that, for the diagnosis of CHF to

be confirmed, there must be both evidence of ventricular dysfunctionand evidence of symptoms due to ventricular dysfunction Thispatient has asymptomatic left ventricular dysfunction after amyocardial infarction

Answer to question 2 D Asymptomatic left ventricular dysfunctionfollowing myocardial infarction represents a newly appreciated area ofleft ventricular dysfunction that is clinically important Patients with leftventricular dysfunction after myocardial dysfunction go on to developeventual CHF, recurrent myocardial infarction, and premature death.The use of ACE inhibitors in this group of patients has been associatedwith an improvement in survival, a reduced likelihood of development

of heart failure, and a reduced rate of recurrent myocardial infarction

β-Blockers and aspirin are indicated after myocardial infarction Theaddition of lipid lowering therapy is specific for this patient, given thehistory of a significant but untreated hyperlipidemia

There is no indication for most types of calcium channel blockersafter myocardial infarction, and their routine use is usuallycontraindicated, especially in patients with known pulmonarycongestion and ventricular dysfunction This is probably due to theirnegative inotropic properties

Based on this patient’s benign clinical course, a cardiaccatheterization after myocardial infarction is not indicated

Answer to question 3 E Again, this patient does not have CHF butrather has asymptomatic left ventricular dysfunction All of thedescriptors are valid, including depressed left ventricular function,dilated left ventricle, and prior history of hypertension, but again thelack of symptoms prevents one from making a diagnosis of heart failure.Answer to question 4 B The data listed in A are not indications forheart transplantation A maximal oxygen consumption greater than

20 ml/kg per min is consistent with a good short-term prognosis anddoes not suggest that transplantation is indicated Similarly, hearttransplantation is not done on the basis of a depressed left ventricularejection fraction alone

2 years ago After 2 more weeks of malaise, cough, and fatigue, thepatient developed difficulty sleeping and vague abdominaldiscomfort He then presented to a university hospital emergencyroom where he was evaluated by a senior medical student He did notuse tobacco or alcohol, and had no prior illnesses

Examination Physical examination: the patient appeared seriously

ill Extremities cool Pulse: 120 beats/min, with pulsus alternans.Blood pressure: 80/60 mmHg Jugular venous pulse: 12 cm at 45°.Parasternal lift First heart sound: normal Second heart: normal.Third and fourth heart sounds were present, along with a grade 3/6mitral holosystolic murmur Chest examination: diffuse crackles tomid-chest Abdominal examination: soft abdomen, liver span 16 cm

No peripheral edema Femoral and popliteal pulses: all palpable andequal Carotid pulses: normal, no bruits

Investigations Chest x ray: markedly enlarged cardiac shadow;

blunted costophrenic angles; enlarged pulmonary arteries; diffuse

pan-lobar infiltrates in an alveolar pattern Electrocardiogram: sinustachycardia, biatrial overload, prominent voltage, diffuse non-specificST-T wave changes Laboratory tests: hemoglobin 12 g/dl (120 g/l),sodium 131 mEq/l (131 mmol/l), creatinine 2·2 mg/dl (194µmol/l),aspartate aminotransferase 125 U/l (2·1µkat/l; normal range0–0·58 µkat/l), alanine aminotransferase 100 U/L (1·7µkat/l), alkalinephosphatase 235 U/l (Normal range 30–120 U/l); total bilirubin2·1 mg/dl (36µmol/l; normal range 5·1–17µmol/l); thyroid functiontests normal Echocardiogram: severe depression of left ventricularsystolic function, left ventricular diastolic diameter 8·2 cm (normal

<6 cm), left ventricular ejection fraction 0·15, dilated left atrium,moderately severe mitral insufficiency, moderate tricuspidinsufficiency, estimated right ventricular systolic pressure 56 mmHg.Right heart catheterization: cardiac output 2·8 l/min (normal

>4·0 l/min), right atrium 20 mmHg (normal 2–10 mmHg), rightventricle 60/20 mmHg (normal range 15–30/2–10 mmHg),pulmonary artery 60/35 mmHg (normal range 15–30/5–10 mmHg),wedge pressure 33 mmHg (normal 5–14 mmHg), mixed venous saturation49% (normal >60%), systemic vascular resistance 1428 dynes·s/cm5(143 kPa·s/l) Endomyocardial biopsy: normal myocardial cells withsparse interstitial inflammatory infiltrate

Hospital day 3 For the first 2 hospital days the patient was treated

with oral medications while undergoing the hospital evaluationoutlined above He remained uncomfortable throughout the first

48 hours The patient awoke with nausea and extreme malaise Hisblood pressure was 65 mmHg He had a witnessed syncopal episodewith telemetry demonstrating a wide complex tachycardia at

175 beats/min Emergent direct current cardioversion was requiredtwice The patient was transferred to intensive care unit A right heartcatheter was placed, with findings identical to those noted above

Hospital day 20 After intensive medical therapy the patient was

recovering well He became ambulatory His blood pressure was116/70 mmHg and his heart rate was 68 beats/min His cardiacexamination was normal Repeat echocardiography revealed a leftventricular ejection fraction 0·25 with a small apical shadow, consistentwith a ventricular clot Three months later, echocardiographydemonstrated an ejection fraction of 0·54 One month later he returned

to his usual employment

Questions

1 The diagnosis of CHF was not originally suspected because

of which of the following? (A) The patient had no clinicalevidence of heart disease at the onset of his illness (B) Thepatient’s demographics were atypical for the diagnosis of heart

failure (C) No signs or symptoms of heart failure were present atthe onset of his illness (D) The diagnosis of CHF can be difficult todiscriminate from atypical pneumonia (E) A and C (F) B and D.

2 At the time of hospital presentation, this patient had CHF of whatseverity? (A) Class I (B) Class II (C) Class III (D) Class IV (E) Thepatient did not have CHF at the time of presentation

3 The diagnostic right heart catheterization revealed whichhemodynamic profile? (A) Increased preload (B) Decreasedafterload (C) Increased afterload (D) Normal cardiac index (E) Aand C (F) B and D (G) None of the above

4 The hemodynamic findings are consistent with which ofthe following? (A) Septic shock (B) Cardiogenic shock.(C) Hypovolemic shock

5 Regarding the dramatic decompensation on day 3, which of thefollowing statements is correct? (A) Ventricular tachycardia is anunexpected complication (B) The presence of ventriculartachycardia represents a serious negative prognostic factor (C)This patient should be treated with antiarrhythmic agentsindefinitely in view of this life-threatening episode of ventriculartachycardia

6 What is the best therapy at the time of transfer to the intensivecare unit? (A) Oxygen, high dose oral diuretics, high dosedopamine, and broad spectrum antibiotics (B) Dobutaminetitrated to a cardiac index greater than 2·5 l/min per m2, andparenteral diuretics, oxygen, lidocaine, and intravenousnitroprusside (C) High dose steroid therapy, intravenous immuneglobulin, and norepinephrine

Answers

Answer to question 1 F This patient had CHF probably due to acutemyocarditis Because he does not represent the usual patient affectedwith CHF and because upper respiratory illnesses are so common inhis age range, the diagnosis of heart failure was missed This is afrequent occurrence in daily practice The evidence for heart failurewas present in the beginning, with cough and fatigue as well as theresting tachycardia In this case, the diagnosis of CHF was not madeeven though symptoms were present

Answer to question 2 D By the time this patient was admitted thediagnosis of heart failure was obvious and he was critically ill Thepresence of symptoms at rest is consistent with class IV CHF, whichcarries a 70% 1 year mortality

Answer to question 3 E

Answer to question 4 B A review of the hemodynamic profiledemonstrates severe left ventricular dysfunction The cardiac output

is severely depressed The preload is markedly increased, given thepulmonary capillary wedge pressure of 33 mmHg and the centralvenous pressure of 20 mmHg The afterload is also increased, based

on a calculated systemic vascular resistance in excess of

1400 dynes·s/cm5 The profile of severely reduced cardiac output andincreased filling pressures with a markedly elevated peripheralresistance is consistent with the diagnosis of cardiogenic shock

Answer to question 5 B For patients with heart failure the incidence

of ventricular arrhythmias approaches 75% and the presence ofcomplex ventricular rhythm disturbances, including ventriculartachycardia, approaches 50% Ventricular tachycardia is an expectedcomplication of severe heart failure Despite the prevalence ofventricular arrhythmias in heart failure, no data as yet suggest thatmedical therapy can modify the rate of death due to sudden cardiacevents Antiarrhythmic therapy is not necessarily indicated on achronic basis Nevertheless, when serious ventricular arrhythmiascomplicate CHF, the prognosis is noted to be quite poor

Answer to question 6 B At the time of transfer to the intensive careunit, this patient is seriously ill having just been resuscitated from acardiac arrest The right heart catheterization confirms poorventricular function The goal of management is to improve thecardiac output, reduce the elevated filling pressures, providesupplemental oxygen, and initiate prophylactic therapy forventricular arrhythmias The addition of nitroprusside is of benefitbecause of its vasodilator properties and ability to reduce afterload.The choices listed in A are not inappropriate except for the use oforal diuretics In a critically ill patient with evidence of central venouspressure elevation and elevated liver function tests consistent with acongested liver, it is unwise to continue to administer oral agents thatwill have an unpredictable absorption and therefore an unpredictableresponse

The biopsy evidence of acute myocarditis suggests thatimmunosuppressive therapy may be of benefit to resolve this acuteinflammatory process The available data demonstrate that thespontaneous recovery rate from such an illness is as high as 40–50%,which is identical to the recovery rate seen with immunosuppressivetherapy but without the toxicity of steroids Supportive care remainsthe best option for patients with acute onset CHF, even if myocarditis

is biopsy proven

Case 10.3

A 69-year-old woman with a longstanding history of essentialhypertension presents to the primary care clinic for routineevaluation She initially denied any specific complaints at the presenttime On further questioning she notes that she has had anunexplained weight gain She also describes frequent episodes offatigue, which she attributes to “old age” She is unable to take herevening walk without resting halfway through Her family thinks she

is well and simply needs to rest more frequently Past history:

a 20 year history of documented hypertension, intermittentcompliance with medications, and no history of stroke or renaldisease; overweight by 30 lb (13·6 kg) for 30 years; and an active 13pack-year history of smoking Current medications: verapamil 80 mgthree times daily and hydrochlorothiazide 75 mg/day

Examination Physical examination: the patient appeared normal.

Pulse: 96 beats/min, normal character Blood pressure: 170/95 mmHg.Jugular venous pulse: normal Cardiac impulse: displaced laterally,diffuse First heart sound: normal Second heart sound: split normally

on inspiration No added sounds or murmurs Chest examination:normal air entry, fine basilar crackles Abdominal examination: softabdomen, liver tender to palpation, no masses Normal liver span.Trace ankle edema Carotid pulses: normal, no bruits

Investigations Chest x ray: clear lung fields, cardiothoracic ratio of

0·65 Electrocardiogram: sinus tachycardia, left atrial overload, leftventricular hypertrophy Laboratory findings: hemoglobin 10 g/dl(100 g/l), creatinine 2·9 mg/dl (256µmol/l), potassium 3·5 mEq/l(3·5 mmol/l), glucose 160 mg/dl (8·9 mmol/l)

Questions

1 Does this patient have CHF? (A) Yes – she has a known history ofhypertension (B) No – there is no assessment of ventricularfunction to establish the diagnosis of CHF (C) No – she has poorlycontrolled hypertension (D) Yes – she has probable hypertensiveheart disease and symptoms of volume overload (E) There areinsufficient data to make the diagnosis

2 What is the next most appropriate step in the evaluation?(A) Evaluation for coronary artery disease (B) Echocardiogram.(C) Both A and B (D) Neither A nor B – all of the data needed areavailable already

3 What is the mortality risk over the next year based on the severity

of her illness at the present time? (A) 5% (B) 10–15% (C) 30%.(D) 70%

4 She seeks a second opinion and undergoes a diagnostic cardiaccatheterization Results: left ventricular ejection fraction 0·35,diffuse mild global hypokinesis, left ventricular end-diastolicpressure 35 mmHg; normal coronary arteries Based on thesefindings, what is her major pathology? (A) Systolic dysfunction.(B) Diastolic dysfunction (C) Both A and B (D) Neither A nor B.(E) None of these – she has a primary idiopathic dilatedcardiomyopathy.

5 Based on the current diagnosis, which of these regimens wouldrepresent the best medical therapy? (A) Captopril 6·25 mg threetimes daily, furosemide 10 mg twice daily, and digoxin0·37 mg/day (B) Verapamil 240 mg three times daily andhydrochlorothiazide 100 mg/day (C) Coumadin 10 mg/day,nifedipine 60 mg three times daily, metolazone 2·5 mg/day,bumetamide 1 mg/day, and potassium chloride 10 mEq/day(10 mmol/day) (D) Enalapril 10 mg twice daily, furosemide

40 mg twice daily, digoxin 0·25 mg every other day, andpotassium chloride 10 mEq/day (10 mmol/day) (E) She needs to

be referred for consideration of cardiac transplantation

Answers

Answer to question 1 D The diagnosis of heart failure is made withhypertensive heart disease (lengthy history of hypertension and leftventricular hypertrophy with cardiomegaly) and CHF symptoms.Answer to question 2 C This is a newly appreciated diagnosis of heartfailure Therefore, an assessment of ventricular function is indicated todetermine the etiology and extent of left ventricular dysfunction It isappropriate to evaluate for coronary artery disease because thisremains the most common cause of heart failure Moreover, thispatient has a number of important risk factors, includinghypertension, smoking, obesity, and lack of postmenopausal estrogentherapy

Answer to question 3 C This patient has symptoms consistent withclass III heart failure Although these patients are ambulatory andcomfortable at rest, they carry a very worrisome prognosis over theshort term

Answer to question 4 C Given that this patient has had longstandinghypertension, the diagnosis of a primary cardiomyopathy cannot bemade The left ventricular systolic function is depressed based on aleft ventricular ejection fraction below 0·40, and the diastolic function

is similarly impaired on the basis of an elevated left ventricular

end-diastolic pressure As a consequence, this patient has both systolicand diastolic dysfunction This is a common observation in patientswho have heart failure due to chronic hypertension.

Answer to question 5 D This patient has several contraindications tocardiac transplantation in view of her advanced age and renalinsufficiency She has not yet had an appropriate trial of medicaltherapy that might result in substantial improvement in hersymptoms The choice of appropriate medical therapy for patientswith heart failure is a critical question Option A includes asubtherapeutic dose of an ACE inhibitor and daily administration ofhigh dose digoxin therapy, which is not likely to be well tolerated inthis patient with renal insufficiency Option B includes high dosecalcium channel blocker therapy, which, although intriguing because

of the diastolic dysfunction, is not indicated because the knownnegative inotropic action of this drug will probably exacerbate heartfailure Thiazide diuretics are not likely to be effective, even in highdoses, in a patient with renal insufficiency Option C includes the use

of anticoagulants, which are not routinely indicated unless the riskfor clot formation is exaggerated because of atrial fibrillation, mitralvalve disease, or known prior emboli Even though nifedipine is avasodilator, its negative inotropic action once again makes it asuboptimal choice in the management of heart failure Only option

D includes an appropriate dose of ACE inhibitor, reduced dose ofdigoxin, loop diuretic, and modest potassium supplementation

Case 10.4

A 37-year-old woman 2 years postpartum presents for evaluation ofdyspnea She describes a normal pregnancy and a benign postpartumcourse immediately after delivery She now notes that it is much moredifficult for her to complete her tasks at work She previously rode astationary bike 30 min a day three times per week She now has toomuch fatigue She has recently experienced stress in her married lifebecause she is always tired She twice noted over the past month thatshe has nearly passed out Past history: no illnesses or surgery;she drinks two to three glasses of wine nightly and smokes one ortwo cigarettes two or three times per week Family history: a distantcousin died suddenly at age 31 years; no autopsy was conducted.Medications: oral contraceptives

Examination Physical examination: the patient had dusky lips.

Pulse: 96 beats/min, normal character Blood pressure: 90/70 mmHg

in right arm Jugular venous pulse: >15 cm with ‘v’ waves Cardiacimpulse: parasternal lift First heart sound: normal Second heart

sound: loud Third heart sound: louder with inspiration 3/6holosystolic murmur at lower left sternal edge Chest examination:normal air entry, no rales or rhonchi Abdominal examination: liverenlarged and pulsatile Trace peripheral edema.

Investigations Chest x ray: enlarged main pulmonary arteries with

oligemia of the lung fields; diminished retrosternal air space.Electrocardiogram: sinus tachycardia; right atrial overload; axis of(+)120° Prominent RSR’ in leads V1–V3 Anterior ST depression withT-wave inversion

Questions

1 The differential diagnosis includes which of the following?(A) CHF (B) Primary pulmonary hypertension (C) Atrial septaldefect (D) A and B (E) A and C (F) All of these

2 The next most appropriate step in the work up would be which ofthe following? (A) Work up for mediastinal tumors based on the

abnormal x ray film (B) Echocardiogram and right heart

catheterization (C) Left heart catheterization (D) Connectivetissue disease work up (E) A and C (F) B and D

3 After another near syncopal episode she returned and wasadmitted A Swan–Ganz catheter was placed and demonstratedthe following findings: pulmonary artery pressure 90/45 mmHg,pulmonary capillary wedge pressure 6 mmHg, cardiac output

3 l/min, right atrial pressure 20 mmHg, right atrial oxygensaturation 58%, pulmonary artery oxygen saturation 61% Themost appropriate therapy for this patient includes which of thefollowing? (A) Captopril 75 mg three times daily, furosemide

80 mg/day, and potassium chloride 20 mEq/day (20 mmol/day).(B) Digoxin 0·25 mg/day and furosemide 20 mg/day (C)Nifedipine 60 mg every 6 hours, hydrochlorothiazide 50 mg/day,and coumadin 5 mg/day

4 After 2 years she began to fail on the above medical therapy She

is placed on oxygen at 4 l/min and a continuous prostacyclininfusion Which is the most appropriate treatment option?(A) Surgical repair of congenital heart disease (B) Hearttransplantation evaluation (C) Heart lung transplant evaluation.(D) Lung transplantation evaluation

Answers

Answer to question 1 F All of the choices comprise an appropriatedifferential diagnosis for a young patient who presents with dyspneaand evidence of at least right ventricular dysfunction Adult forms ofcongenital heart disease are uncommon but should be considered in

atypical cases, especially in the younger patient This patient hasevidence of right heart failure and pulmonary hypertension Thehistory of progressive dyspnea in a young woman is associated withthis diagnosis The examination contains impressive evidence forright heart dysfunction: “v” waves consistent with tricuspidregurgitation; a prominent second heart sound consistent withprominent closure of the pulmonic valve; a parasternal lift due toright ventricular pressure or volume overload and a right sided thirdhear sound consistent with right ventricular dilatation; tricuspidinsufficiency; hepatomegaly; and peripheral edema.

Answer to question 2 F The retrosternal fullness on chest x ray film

does not represent a mediastinal tumor but rather right ventricularenlargement, which is otherwise difficult to observe on a chestradiograph A left heart study is not indicated based on minimal if anyrisk factors being present The diagnosis of pulmonary hypertensionneeds to be confirmed or ruled out An echocardiogram allows one toconfirm the extent of right ventricular disease and to estimatenon-invasively the pulmonary artery pressure It also is quite useful inevaluating adult congenital heart disease The right heartcatheterization is the definitive study in this case The diagnosis ofprimary pulmonary hypertension cannot be established untilconnective tissue disorders have been ruled out

Answer to question 3 C The right heart catheterization confirms thediagnosis of primary pulmonary hypertension Left heart failure may

be associated with striking elevations in pulmonary artery pressurebut with associated elevations in pulmonary capillary wedge pressure.The finding of a normal wedge pressure with near systemicpulmonary artery pressures confirms the diagnosis The measuredoxygen saturations are not consistent with a left to right shunt andeffectively rule out the common adult congenital heart diseases Thebest available medical therapy at present for primary pulmonaryhypertension includes calcium channel blockers, gentle diuretics, andanticoagulation

Answer to question 4 D The use of prostacyclin (a prostaglandinthat causes vasodilatation) is an effective strategy for relief ofsymptoms in patients with primary pulmonary hypertension whohave failed high dose calcium channel blocker therapy Lungtransplantation is the last treatment option after all medical attemptshave failed Even though this patient has evidence of right ventriculardysfunction, it appears that successful lung transplantation for thisillness relieves the afterload on the right ventricle and normalfunction returns A heart–lung transplant is therefore not indicated

The 1 year survival for heart–lung transplantation is approximately50% A heart transplantation alone does not solve the problem withpulmonary hypertension In fact, patients cannot receive a hearttransplant until significant pulmonary hypertension not due to leftheart failure has been ruled out The available data have revealed thatpatients with pulmonary hypertension, that is fixed, do not do wellwith heart transplantation even if overt heart disease is the majorpathology The heart transplant work up for all potential recipientsincludes a right heart catheterization for this reason A lungtransplantation is the only way to prolong survival once the patienthas reached the point of continuous prostacyclin infusion.

References

1 Hosenpud JD, Greenberg BH Congestive heart failure Pathophysiology, diagnosis, and

comprehensive approach to management New York: Springer-Verlag, 1994.

2 Felker GM, Thompson RE, Hare JM, et al Underlying causes and long-term survival

in patients with initially unexplained cardiomyopathy N Engl J Med 2000;

Heart Failure Circulation 1995;92:2764–84.

5 Hunt SA, Baker DW, Chin MH, et al ACC/AHA Guidelines for the Evaluation and

Management of Chronic Heart Failure in the Adult: executive summary: a report

of the American College of Cardiology/American Heart Association Task Force on

Practice Guidelines J Am Coll Cardiol 2001;38:2101–13.

6 The Digitalis Investigation Group The effect of digoxin on mortality and

morbidity in patients with heart failure N Engl J Med 1997;336:525–33.

7 Crawford M Cardiology clinics: congestive heart failure, vol 12 Philadelphia:

WB Saunders, 1994.

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mortality in patients with severe heart failure N Engl J Med 1999;341:709–17.

9 Cohn JN, Johnson G, Ziesche S, et al A comparison of enalapril with isosorbide dinitrate in treatment of chronic congestive heart failure N Engl J Med

hydralazine-1991;325:303–10.

10 The CONSENSUS Trial Study Group Effects of enalapril on mortality in severe

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12 Frishman WH Carvedilol N Engl J Med 1998;339:1759–65.

13 Califf RM, O'Connor CM β -Blocker therapy for heart failure The evidence is in,

now the work begins JAMA 2000;283:1335–7.

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333:77–82.

11: Congenital heart disease

M ELIZABETH BRICKNER

Congenital heart disease occurs in fewer than 1% of all live births.Although the majority of cases are diagnosed in childhood, patientsmay not present until adulthood Improvements in both medicaltherapy and surgery have also resulted in an increasing number ofpatients with congenital heart disease surviving into adulthood Thepresent discussion focuses on the types of congenital heart diseasethat may present for the first time in adulthood.1–4

Left to right shunts

Atrial septal defects

Atrial septal defects account for 5–10% of all congenital heart defects andare more common in females than males (2:1 female : male ratio) Thereare three common anatomic types (Figure 11.1) Ostium secundum defectsare located in the middle portion of the interatrial septum and are the mostcommon type (70%) Ostium primum defects (15%) are located in theinferior portion of the interatrial septum and are often associated withabnormalities of the mitral and tricuspid valves (clefts) that may result insignificant valve regurgitation Sinus venosus atrial septal defects (10–15%)are located in the superior portion of the interatrial septum, at the junction

of the superior vena cava and the right atrium Partial anomalouspulmonary venous drainage is commonly associated with sinus venosusdefects, and usually involves drainage of one (but occasionally both) of theright pulmonary veins into the superior vena cava or right atrium Sinusvenosus defects may be associated with ectopic atrial rhythms

Atrial septal defects result in continuous left to right flow across theinteratrial septum, and the size of the defect and the difference incompliance between the pulmonary and systemic circulationsdetermine the magnitude of the shunt The resulting volume overload

of the right atrium and right ventricle leads to enlargement of thosechambers Atrial septal defects are usually asymptomatic in childhoodand early adulthood, and may not be diagnosed With increasing age,symptoms of fatigue, exercise intolerance, palpitations, and exertionaldyspnea become more common

The cardinal finding on physical examination is a widely splitsecond heart sound (S2) that does not vary with respiration (i.e fixedsplitting) because of delay in pulmonary valve closure in patients with

normal pulmonary pressures and low pulmonary vascular resistance.

A parasternal lift due to a prominent, hyperdynamic right ventricularimpulse may be palpated A mid-systolic ejection murmur over thepulmonic area is invariably present, and is caused by increased bloodflow across the pulmonic valve (Flow across the atrial septal defectitself does not cause a murmur.) If the shunt is large the increased flowacross the tricuspid valve may result in a mid-diastolic rumblingmurmur at the lower left sternal border

Over time, in response to the increased pulmonary blood flow,pulmonary vascular resistance and pulmonary pressures may increase

As pulmonary hypertension develops, the physical examinationfindings change Splitting of S2 becomes narrower as pulmonarypressures increase and the pulmonary component of S2 (P2) becomes

LA

LV RV RA

Right pulmonary veins

Sinus venosus defect

Ostium secundum defect

Ostium primum defect

LA

LV RV

RA LA

LV RV RA

Figure 11.1 Anatomic types of atrial septal defects (a) Ostium secundum defect with normal pulmonar y venous connections (b) Ostium primum defect with an abnormal mitral valve (cleft in anterior mitral leaflet) (c) Sinus venosus defect with associated par tial anomalous pulmonar y venous drainage (right pulmonar y veins draining into the superior vena cava) LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle

(a)

(c)

(b)

louder As pulmonary vascular resistance increases, the magnitude ofthe left to right shunt decreases and the pulmonary flow murmur alsodecreases As the pulmonary vascular resistance rises, predominantright to left shunting may ensue with resulting hypoxia, cyanosis, andclubbing (Eisenmenger physiology).

Classic electrocardiographic findings in an uncomplicated ostiumsecundum atrial septal defect include right axis deviation, rightventricular hypertrophy, and incomplete right bundle branch block.This delay in right ventricular activation may be due either to volumeoverload or to actual conduction delay in the right bundle.Electrocardiographic evidence of right ventricular hypertrophy may bepresent as well Left axis deviation suggests an ostium primum atrialseptal defect and an ectopic atrial rhythm suggests the presence of a

sinus venosus type of defect The chest x ray film in an uncomplicated

atrial septal defect demonstrates cardiomegaly, with enlargement ofthe right atrium and ventricle and increased pulmonary vascularmarkings (“plethora”) indicative of increased pulmonary blood flow.Enlargement of the main pulmonary arteries may be seen

The diagnosis of an atrial septal defect can be made byechocardiography, which demonstrates enlargement of the right atriumand ventricle, the location and size of the defect, and the direction of theintracardiac shunt Ostium secundum and ostium primum defects canusually be seen by transthoracic echocardiography, whereas only 50% ofsinus venosus defects can be seen using this technique Transesophagealechocardiography is a superior technique for demonstrating the sinusvenosus type of defects Cardiac catheterization is another technique fordiagnosing atrial septal defects A “step-up” in oxygen saturation due toleft to right shunting across the defect is demonstrated by taking bloodsamples proximal to the shunt (from the vena cavae) and distal to theshunt (from the right ventricle or pulmonary artery) The ratio ofpulmonary to systemic blood flow (Qp/Qs) can be calculated from theseoxygen saturation data to determine the size of the shunt Cardiaccatheterization also allows measurement of pulmonary pressures andpulmonary vascular resistance In older patients, coronary angiography

is also performed to diagnose concomitant coronary artery disease.Eisenmenger’s syndrome (pulmonary hypertension with reversed orbidirectional shunt at atrial, ventricular, or aortopulmonary level) is

an uncommon complication of atrial septal defects, and occurs infewer than 10% of longstanding cases appearing in adulthood Morecommonly, patients with untreated atrial septal defects develop rightheart failure and atrial arrhythmias as a consequence of volumeoverload of the right ventricle In these patients symptoms usuallydevelop by the fourth or fifth decade of life

Prophylaxis for bacterial endocarditis is not required for atrial septaldefects unless valvular defects are also present Closure of the defect is

recommended for all atrial septal defects of significant size(pulmonary to systemic flow ratio >2:1) unless pulmonary vascularresistance is prohibitively high In addition to surgical closure, thereare percutaneous devices that can be can be used in suitablecandidates With a pulmonary to systemic vascular resistance ratio ofgreater than 0·7, surgery is associated with increased morbidity andmortality, and shunt closure is almost always contraindicated Surgeryshould be done as early as possible after the defect is detected Closurebefore age 40 years may allow normal cardiac size and function toreturn, whereas closure in older patients is often associated withresidual right heart failure and atrial arrhythmias Transcatheterclosure of small to moderate size defects represents a new option forsome patients, although long-term results are not available and directcomparisons with surgical outcomes have not been conducted.

Ventricular septal defects

Ventricular septal defects are among the most common forms ofcongenital heart disease (20–30% of all defects) and are morecommon in males Ventricular septal defects may involve themembranous septum (70%), the muscular septum (25%), thesupracristal region (involving the annuli of the aorta and pulmonaryartery; 5%), or the inlet portion of the septum (under the mitral andtricuspid valves; Figure 11.2) Both perimembranous and musculartypes of ventricular septal defects may close spontaneously (as many

as 50%), usually within the first year of life

Because ventricular septal defects usually produce a loud murmur,they are commonly detected in childhood Small defects result insmall shunts and are usually asymptomatic Moderate to large defectsresult in volume overload of the left atrium and left ventricle, and areassociated with symptoms such as poor exercise tolerance andcongestive heart failure These larger defects are usually diagnosed inchildhood With larger shunts, pulmonary pressures and pulmonaryvascular resistance may be elevated With severe pulmonaryhypertension, shunt reversal occurs (Eisenmenger’s syndrome) Whenventricular septal defects are discovered in adulthood, they are usuallysmall (an incidental finding) or the patient has had prior surgery orhas developed a complication related to the defect

The physical examination, electrocardiographic, and chest x ray

findings depend on the size of the ventricular septal defect and theamount of pulmonary hypertension With small defects (<0·5 cm2), thesmall left to right shunt does not result in significant volume overload

to the heart The left to right shunt across the defect causes a palpablethrill and a loud, holosystolic murmur that is heard best along the leftsternal border The S2is normal The electrocardiogram and chest x ray

film are normal With defects of moderate size (0·5–1·0 cm2) volumeoverload of the left atrium and left ventricle occurs A systolic thrill andholosystolic murmur are again present and a mid-diastolic rumble can

be heart over the mitral area, indicating increased blood flow across thevalve Left ventricular hypertrophy is seen on the electrocardiogram,and pulmonary plethora (increased pulmonary vascular markings) is

seen on the chest x ray film With large defects (>1·0 cm2) left sidedthird heart sound (S3) and fourth heart sound (S4) are usually present,

in addition to a palpable thrill and systolic and diastolic murmurs Signs

of pulmonary hypertension may be present as well, with a palpableparasternal lift due to right ventricular pressure overload and a loud P2

on auscultation At this stage the electrocardiogram demonstrates

biventricular hypertrophy and the chest x ray film shows frank

cardiomegaly in addition to pulmonary plethora With development ofirreversible pulmonary hypertension and shunt reversal (Eisenmenger’ssyndrome), the murmurs and systolic thrill disappear, the S2 (P2)

LA

Ao

LA

LA PA

Muscular defect Inlet defect

Outlet defect Paramembranous defect

LV LV

LA

LV RV RA

Figure 11.2 Anatomic types of ventricular septal defects (a) Paramembranous defects are located beneath the aor tic valve, adjacent to the tricuspid valve Outlet defects are related to both the aor tic and pulmonar y valves (b) Muscular defect (c) Inlet defect, underlying the mitral and tricuspid valves Ao, ascending aor ta; L, left coronar y cusp of aor tic valve; LA, left atrium; LV, left ventricle; N, non-coronar y cusp; PA, pulmonar y ar ter y; R, right coronar y cusp of aor tic valve; RA, right atrium;

RV, right ventricle

(a)

(c) (b)

becomes narrow or even single, and cyanosis and clubbing appear.The electrocardiogram now demonstrates pure right ventricular

hypertrophy The chest x ray film may now show dilated main

pulmonary arteries and small, “pruned” distal pulmonary vessels withrelative oligemia of the vascular markings

The diagnosis of a ventricular septal defect can be made bytransthoracic echocardiography, which demonstrates the location andsize of the defect and the direction of the shunt With moderate to largeshunts, left atrial and ventricular enlargement is seen Transesophagealechocardiography is needed only for patients with technically inadequatetransthoracic imaging Cardiac catheterization is also used to diagnoseleft to right shunting associated with ventricular septal defects bydemonstrating a “step-up” between the right atrium and the pulmonaryartery, or by demonstrating contrast shunting from the left to rightventricle The ratio of pulmonary to systemic blood flow (Qp/Qs) iscalculated to determine the size of the shunt and pulmonary pressuresand pulmonary vascular resistance is also calculated If pulmonaryvascular resistance is markedly elevated (>70% of systemic vascularresistance), then shunt closure is contraindicated

The development of severe pulmonary hypertension with shuntreversal causing cyanosis (Eisenmenger’s syndrome) is a dreadedcomplication of ventricular septal defects, occurring in 10–25% (morecommonly than with atrial septal defects) In patients with ventricularseptal defects, this syndrome usually presents in the first or seconddecade of life Despite severe disease, survival to early adulthood iscommon Infective endocarditis is another complication in patientswith ventricular septal defects The tricuspid valve, or the rightventricular endocardium itself, where the turbulent left to right “jet”strikes, is usually involved Other acquired complications include thedevelopment of aortic regurgitation and subaortic stenosis

When a ventricular septal defect is diagnosed it is important toassess the magnitude of the shunt and the degree of pulmonaryvascular disease Surgical closure is recommended for significant left

to right shunts (pulmonary to systemic flow ratio 2:1) If significantpulmonary hypertension is suspected, then cardiac catheterization isnecessary to measure pulmonary vascular resistance As for all shuntlesions, significant pulmonary vascular disease (pulmonary vascularresistance to systemic vascular resistance ratio greater than 0·7) is acontraindication to shunt closure because it is likely to result in acuteright heart failure and death Prophylaxis for bacterial endocarditis isrequired for all ventricular septal defects, regardless of their size.Continued antibiotic prophylaxis is also recommended for anypatients with a residual ventricular septal defect after surgicalclosure

Patent ductus arteriosus

The ductus arteriosus is a normal part of the fetal circulation,connecting the pulmonary trunk and the descending aorta just distal

to the left subclavian artery so that most of the fetal right ventricularoutput bypasses the unexpanded lungs and travels to the placentawhere oxygenation occurs Persistence of this communication afterbirth is referred to as a patent ductus arteriosus (Figure 11.3) It ismore common in females than in males (3:1) and may be seen inassociation with maternal rubella, and pulmonary disease in infantsand in premature infants A patent ductus arteriosus produceshemodynamic changes that are similar to those seen with ventricularseptal defects The left to right shunt produces a volume load on theleft heart, and the magnitude of the shunt depends on the size of theductus and the pulmonary vascular resistance

The clinical manifestations of a patent ductus arteriosus depend onthe size of the shunt Patients with a small shunt are asymptomatic,whereas large shunts can result in recurrent pulmonary infections,poor exercise tolerance, exertional dyspnea, and congestive heartfailure A large ductus can cause compression of the recurrentlaryngeal nerve, resulting in hoarseness

The classic finding on physical examination is a “machinery-type”continuous murmur (for example, a murmur that persists throughoutsystole and continues past the second heart sounds) at the left uppersternal border With a small ductus, the remainder of the physical

RV

LV

LA Ao

Figure 11.3 Patent ductus ar teriosus Ao, ascending aor ta; LA, left atrium; LV, left ventricle; PA, pulmonar y ar ter y; RA, right atrium; RV, right ventricle

examination is normal, as are the electrocardiogram and the chest

x ray findings With moderate to large shunts, the precordium is

hyperactive, peripheral pulses are bounding (due to rapid run-offthrough the ductus), and a diastolic rumble is heard across the mitralvalve, indicating an increased volume of blood flow The pulmonarycomponent of S2 is usually increased The electrocardiogramdemonstrates left ventricular hypertrophy and may show rightventricular hypertrophy as well Cardiomegaly with pulmonary

plethora is seen on the chest x ray.

As with other shunts, pulmonary vascular disease may developresulting in Eisenmenger’s syndrome If the Eisenmenger physiology ispresent, then S2is loud and single, and the continuous murmur and themitral diastolic murmur are no longer heard Differential cyanosis may

be present (cyanosis of the lower extremities) as desaturated blood fromthe right to left shunt enters the descending aorta through the ductus.The upper extremities, perfused by unshunted blood, will be acyanotic.The diagnosis of an uncomplicated patent ductus arteriosus can bemade by transthoracic echocardiography, which demonstratescontinuous left to right shunting from the aorta to the pulmonary artery

At cardiac catheterization the shunt can be diagnosed by demonstrating

an oxygen “step-up” in the pulmonary artery or by demonstratingcontrast shunting from the aorta to the pulmonary artery

The presence of a patent ductus increases the risk for infectiveendocarditis, and with significant shunts it increases the risk for heartfailure and Eisenmenger’s syndrome Severe pulmonary vascularobstruction may cause calcification, aneurysmal dilatation, or rupture

of the ductus Closure of the shunt is recommended for all patientsexcept those with Eisenmenger physiology and elderly patients.Quantitation of the shunt size is not important in determining theneed for shunt closure In general, surgical ligation or division of theductus has a low operative mortality and morbidity, althoughcomplications such as damage to the recurrent laryngeal nerve, thephrenic nerve, or the thoracic duct can occur Newer, non-surgicaloptions for closure of the patent ductus arteriosus include “button”devices, “double umbrella” occluders, and spring coils These variousdevices can be placed percutaneously with low complication rates andmay become the procedure of choice for selected patients

Obstructive lesions

Aortic stenosis

Congenital abnormalities of the aortic valve can result in a valvethat is obstructive at birth or may develop progressive obstruction

over time Aortic valve stenosis may be due to bicuspid valves orunicuspid valves Unicuspid valves are inherently stenotic andsymptoms present in infancy and childhood Bicuspid aortic valvesoccur in 1–2% of the general population, more commonly in malesthan in females The bicuspid aortic valve has only two cusps (usually

of unequal size), rather than three normal cusps (Figure 11.4) In 50%

of cases, a raphe or false commissure is seen on the larger of the twoleaflets Bicuspid valves are usually not inherently stenotic and mayfunction normally throughout life In some patients, progressivefibrosis and calcification of the cusps occurs, resulting in progressiveaortic stenosis Bicuspid valves commonly exhibit some degree of

Figure 11.4 Transesophageal echocardiographic images of a normal aor tic valve and a bicuspid aor tic valve A normal aor tic valve in (a) closed and (b) open position, and a bicuspid aor tic valve in (c) closed and (d) open position

aortic regurgitation that may be progressive over time, and infectiveendocarditis is common in patients with bicuspid aortic valves and is

a major cause of aortic regurgitation Bicuspid aortic valves are alsoassociated with coarctation of the aorta, dilatation of the aortic root,and an increased risk for aortic dissection

Patients with bicuspid aortic valves are usually asymptomatic butmay present with symptoms if the valve is dysfunctional Patientswith mild aortic stenosis are usually asymptomatic but patients withmoderate to severe aortic stenosis may present with angina, syncope,

or symptoms of heart failure Typically, patients present withsymptomatic aortic stenosis in their 40s or 50s, whereas patients withdegenerative aortic stenosis typically present at an older age

The physical examination, electrocardiogram, and chest x ray

findings in patients with congenital aortic stenosis are similar to thoseseen in patients with acquired forms of aortic stenosis, except thatbicuspid valves are frequently associated with an ejection click.Echocardiography can document valve anatomy and quantitate theseverity of stenosis Cardiac catheterization is also used to quantitatethe severity of stenosis The management of congenital aortic stenosis

in adults is similar to that for patients with acquired forms of aorticstenosis, and intervention is indicated for symptomatic patients.Valve replacement is required for most patients but balloonvalvuloplasty is an option for a few patients with stenotic valves thatare relatively pliable and non-calcified All patients with bicuspidaortic valves require prophylaxis against bacterial endocarditis

Pulmonic stenosis

Obstruction of the right ventricular outflow tract can occur at thelevel of the valve, in the infundibulum (below the valve), or above thevalve Valvular stenosis accounts for approximately 90% of cases ofpulmonic stenosis and is commonly associated with survival intoadulthood Infundibular stenosis is usually associated with tetralogy

of Fallot or other congenital malformations

Symptoms depend on the severity of the stenosis Patients withtrivial (peak gradient <25 mmHg) or mild stenosis (peak gradient25–50 mmHg) are usually asymptomatic With more significantstenosis, fatigue and exertional dyspnea are common Syncope canalso occur Symptoms of right ventricular failure can occur with severestenosis (peak gradient >75–100 mmHg) Right to left shunt withcentral cyanosis can occur if there is an associated atrial septal defect

or patent foramen ovale in the presence of severe pulmonic stenosis

On physical examination, a parasternal lift may be palpated due toright ventricular pressure overload, and a systolic ejection murmur is

heard along the left sternal border With mild stenosis, the murmurpeaks early, a systolic ejection click is often heard, and P2 is usuallynormal A systolic thrill along the left sternal border may be presentwith mild degrees of stenosis but is more common with moderate tosevere obstruction With increasing degrees of obstruction, the systolicmurmur peaks later, the ejection click often disappears, and P2becomessofter and delayed With severe pulmonic stenosis one may find aprominent “a” wave in the jugular venous pulse and a right ventricular

S4 As the severity of pulmonic stenosis increases the electrocardiogramprogresses from normal to right axis deviation and right ventricularhypertrophy, and eventually a right ventricular strain pattern develops

as well The chest x ray film usually demonstrates normal heart size and

poststenotic dilatation of the main pulmonary artery

Echocardiography demonstrates thickened pulmonary valve leafletswith limited mobility The pressure gradient can be determine by Dopplertechniques, and associated lesions such as interatrial shunts can also bedetected At cardiac catheterization, the pressure gradient between theright ventricle and the pulmonary artery can be measured Balloonvalvuloplasty can also be performed at the time of catheterization and isrecommended as the initial therapy for symptomatic patients withmoderate to severe stenosis Balloon valvuloplasty achieves reductions ingradient that are comparable to those achieved by surgery, but with lowermorbidity and mortality rates Surgery is reserved for patients with otherassociated lesions that require repair or for those in whom balloonvalvuloplasty is not successful No intervention is required forasymptomatic patients with mild to moderate stenosis

Coarctation of the aorta

Coarctation of the aorta accounts for approximately 8% of allcongenital heart disease It is more common in males than in females(ratio 2:1) and is commonly seen in association with Turner’ssyndrome (gonadal dysgenesis in phenotypic women with primaryamenorrhea, short stature, and multiple congenital abnormalities).Bicuspid aortic valves are seen in approximately half of all patientswith coarctation of the aorta Other obstructive lesions of the leftheart (mitral stenosis, subaortic stenosis, aortic stenosis) are alsoassociated with coarctation of the aorta As many as 20% of cases ofcoarctation are undetected in childhood, presenting either inadolescence or adulthood In adults, a ridge, or web, of tissue causingobstruction to flow is present in the aorta just distal to the leftsubclavian artery (Figure 11.5) Collateral circulation to the lowerbody is usually well developed and patients are often asymptomatic(collaterals may be palpated in the posterior intercostal spaces)

Coarctation of the aorta should be suspected in a young adult whopresents with hypertension.

Patients are hypertensive with a higher blood pressure in the armsthan in the legs (>20 mmHg) Simultaneous palpation of the radial andfemoral arteries reveals the femoral pulses to be diminished and delayed.Pulses in the lower extremities are decreased or even absent On cardiacauscultation, an aortic ejection click and increased intensity of the aorticcomponent of S2 (A2) may be heard, with a bicuspid aortic valve.Murmurs may arise from an associated bicuspid aortic valve, from thecoarctation itself, or from collateral arterial flow A systolic ejectionmurmur is commonly heard and a diastolic murmur of aorticinsufficiency may be detected A localized systolic murmur over thespine can be heard at the site of the coarctation Bruits secondary tocollateral flow may be heard both anteriorly (flow through the internalmammary arteries) and posteriorly (flow through the intercostalarteries) If right arm pulses are intact but left arm pulses are absent, thenthe coarctation is proximal to or at the level of the left subclavian artery.The electrocardiogram may be normal (in up to 20%) but left

ventricular hypertrophy is common On chest x ray, the heart size is

normal or only mildly enlarged The ascending aorta may appear

PA Ao

LSA

LCC RCC

RSA

Figure 11.5 Coarctation of the aor ta (postductal type) The area of obstruction is located distal to the left subclavian ar ter y (LSA), near the ligamentum ar teriosum (fine arrow) Ao, aor ta; LCC, left common carotid ar ter y; PA, pulmonar y ar ter y; RCC, right common carotid ar ter y; RSA, right subclavian ar ter y (Thick arrow shows site of coarctation of the aor ta)

dilated (suggesting a bicuspid aortic valve) A “three” sign may beseen, caused by a dilated left subclavian artery above the coarctationand poststenotic dilatation of the aorta below the coarctation Ribnotching is seen in the posterior aspect of the fourth to eighth ribs inolder children and adults as a result of erosion of the rib margins byenlargement of the intercostal arteries.

The diagnosis of coarctation of the aorta can best be confirmed bymagnetic resonance imaging, which can demonstrate the anatomy andassess the degree of obstruction Echocardiography is also useful,particularly in children, in whom the area of coarctation may bedirectly visualized Color Doppler can demonstrate turbulent flowacross the obstruction and the pressure gradient can be measured byDoppler Cardiac catheterization also provides excellent anatomic andhemodynamic definition The pressure gradient across the coarctationcan be measured The lesion itself can be demonstrated by angiography.Identification and correction of coarctation of the aorta isimportant because the median survival for patients with uncorrectedcoarctation of the aorta is in the mid-30s Complications ofcoarctation include left ventricular failure due to longstandinghypertension, endocarditis (occurring either on the associatedbicuspid valve or at the site of the coarctation), dissecting aorticaneurysm, and rupture of the aorta Rupture or dissection mostcommonly occurs in the third or fourth decade of life with anincreased risk during pregnancy Stenosis or regurgitation of theassociated bicuspid aortic valve can also occur

Intervention is recommended when a significant gradient(>30–50 mmHg) is present Options include surgical correction andballoon aortoplasty Surgical repair can be achieved with resectionand end-to-end anastomosis, use of the left subclavian artery as apatch, or use of a Dacron patch Long-term survival after surgicalrepair depends on the age at the time of repair, with best results seenwith repair in infancy and the shortest survival times reported withrepair after age 40 years Persistent hypertension is commonpostoperatively, and appears to be related to increased age at the time

of repair Balloon aortoplasty is an alternative to surgery that appears

to be most appropriate for infants and children, and may be useful inthe setting of postoperative restenosis

Cyanotic congenital heart disease

Tetralogy of Fallot

Tetralogy of Fallot accounts for approximately 10% of all congenitalheart disease and is the most common cyanotic defect presenting in

adulthood (Figure 11.6) The four components of tetralogy are a largeventricular septal defect, overriding of the aorta, obstruction of theright ventricular outflow tract, and right ventricular hypertrophy Theventricular septal defect is large and non-restrictive, which results

in equalization of right and left ventricular pressures Obstruction ofthe right ventricular outflow tract may occur at the level of theinfundibulum (50%), at the level of the pulmonic valve (isolatedvalvular stenosis in 10%), or at multiple levels within the rightventricular outflow tract and pulmonary artery The pathophysiologyand clinical presentation depend on the degree of right ventricularoutflow tract obstruction In the classic form of tetralogy withsignificant stenosis of the outflow tract, pulmonary blood flow isdiminished and pulmonary pressures are low to normal A significantright to left shunt is present, its magnitude determined by the ratio ofpulmonary to systemic vascular resistance Patients present withcyanosis and exertional dyspnea Cyanotic “spells” occur in infantsbut are not seen in adults

Ao

PA

LA RA

RV

LV

Figure 11.6 Tetralogy of Fallot with left aor tic arch (normal orientation) A large non-restrictive ventricular septal defect with an overriding aor ta is shown Obstruction to right ventricular outflow is present (both valvular pulmonic stenosis and infundibular stenosis in this example) with decreased flow into the pulmonar y

ar ter y Flow across the ventricular septal defect is predominantly right to left Right ventricular hyper trophy is present Ao, aor ta; LA, left atrium; LV, left ventricle; PA, pulmonar y ar ter y; RA, right atrium; RV, right ventricle

In contrast to the classic form of tetralogy of Fallot, mild degrees ofobstruction across the right ventricular outflow tract are associatedwith increased pulmonary blood flow and a small to moderate left toright shunt across the ventricular septal defect In this form, thepatient is acyanotic (so-called “pink tetralogy”) and is usuallyasymptomatic However, over time progression of the rightventricular outflow tract obstruction usually occurs, resulting indevelopment of cyanosis and symptoms.

On physical examination in classic tetralogy of Fallot, cyanosis andclubbing are present In the jugular venous pulse “a” and “v” wavesare prominent, and a parasternal lift due to right ventricular pressureoverload may be felt The S2 is usually single (inaudible pulmonarycomponent) A systolic ejection murmur is heard along the sternalborder caused by the outflow tract obstruction, with the intensity andduration of the murmur directly related to the severity of obstruction

A systolic thrill secondary to the outflow tract obstruction may also benoted If there is significant collateral circulation to the lungs fromthe bronchial arteries, then continuous murmurs may be heard in thechest The electrocardiogram demonstrates right axis deviation

and right ventricular hypertrophy On chest x ray, the heart size is

small to normal and is classically “boot-shaped” Pulmonary vascularmarkings are decreased with “oligemia” of the lung fields A rightsided aortic arch is seen in 25% of cases

While most patients with tetralogy of Fallot present with cyanosis

in infancy, some patients may survive to adulthood in the unoperatedstate Symptoms typically worsen with increasing age as the degree ofright ventricular obstruction increases In addition to complaints ofcyanosis and exercise limitations, patients also develop complicationsassociated with cyanotic heart disease, including erythrocytosis,hyperviscosity, coagulation abnormalities, gout, stroke, brain abscess,and infective endocarditis

The diagnosis of tetralogy of Fallot can be made by echocardiography

or cardiac catheterization Echocardiography demonstrates rightventricular hypertrophy, the ventricular septal defect, the overridingaorta, and the level and severity of right ventricular outflow tractobstruction Cardiac catheterization is required if surgical correction isbeing considered The ventricular septal defect with right to leftshunting is demonstrated on ventriculography, and the degree of rightventricular outflow tract obstruction can be measured In addition,coronary angiography is performed to exclude the possibility ofanomalous coronary arteries (seen in 10%)

All patients with tetralogy of Fallot require bacterial endocarditisprophylaxis Surgical correction with patch closure of the ventricularseptal defect and relief of right ventricular outflow tract obstruction is

performed to provide relief of symptoms and improve survival Relief

of right ventricular outflow tract obstruction may involve pulmonaryvalvotomy, enlargement of the pulmonary artery annulus with aprosthetic patch, and resection of infundibular stenosis; in some cases

it requires a prosthetic conduit to bypass the obstruction Surgicalcorrection in uncomplicated forms of tetralogy of Fallot can beperformed with a mortality rate of approximately 5% and results ingood long-term survival Postoperatively, patients need to be followedcarefully because they are at risk for arrhythmias and conductiondisorders, recurrent right heart obstruction, pulmonic insufficiency,right ventricular dysfunction, and complications associated withprosthetic patches, valves, or conduits

Eisenmenger’ syndrome

In patients with left to right shunts and increased pulmonary bloodflow, progressive histologic changes may occur in the pulmonaryvascular bed as a consequence of the increased pulmonary blood flowand pressure These histologic changes occur predominantly in thesmall muscular arteries, ultimately resulting in irreversible pulmonaryhypertension and elevation in pulmonary vascular resistance, acondition referred to as pulmonary vascular obstructive disease Theinitial changes (largely reversible) consist of medial hypertrophy,intimal proliferation, and fibrosis The later stages (irreversible)consist of dilatation and thinning of the vessel wall, development ofplexiform lesions within the lumen of the vessels, and fibrinoidnecrosis of the arteries As pulmonary vascular resistance approaches

or exceeds systemic vascular resistance, the shunt flow becomesbidirectional or predominantly right to left The term “Eisenmenger’ssyndrome” is used to describe patients with shunt reversal due tosevere pulmonary vascular disease

The pathologic changes that occur in the pulmonary vascular bedbegin in childhood but may not result in symptoms until latechildhood or early adulthood Symptoms usually occur earlier withlarge shunts at the level of the aorta or ventricle and later with shunts

at the atrial level Patients commonly present with complaints ofexertional fatigue and dyspnea as well as cyanosis Recurrent episodes

of hemoptysis may occur due to in situ thrombosis of small

pulmonary arteries, recurrent pulmonary emboli with infarction, orhemorrhage from plexiform lesions within the pulmonary vessels.Occasionally, patients may present with massive hemoptysis due torupture of a pulmonary artery Exertional angina may occur because

of right ventricular ischemia Exercise can also result in syncope by

causing a reduction in systemic vascular resistance, increased right toleft shunting, and decreased cerebral oxygenation Syncope or suddendeath also occur as the result of arrhythmias Arrhythmias mayresult in rapid clinical deterioration Right heart failure is a latecomplication of pulmonary vascular obstructive disease and is morecommonly seen in older patients.

Patients with significant right to left shunting have chronichypoxemia, stimulating erythropoietin production and resulting in anelevated red blood cell mass (erythrocytosis) Marked erythrocytosis canresult in symptoms of hyperviscosity (headache, myalgias, paresthesias,blurry vision, dizziness, and exertional dyspnea) The increase in red cellturnover can result in calcium bilirubinate gallstones, placing patients atrisk for acute cholecystitis Patients may develop anemia secondary toiron deficiency (most commonly) or folate or vitamin B12deficiency, adiagnosis that can easily be missed in a patient who presents withhemoglobin within the “normal” range The development of irondeficiency is detrimental in these patients because iron deficiency results

in increased blood viscosity, which can worsen hyperviscositysymptoms Coagulation abnormalities including factor deficiencies andplatelet dysfunction also occur, placing patients at risk for boththrombotic and hemorrhagic complications Brain abscess is anuncommon complication, resulting from paradoxic embolism ofinfected material Patients frequently develop impaired renal function.Impaired excretion of uric acid resulting in hyperuricemia is commonand is a marker of underlying renal dysfunction

The predominant finding on physical examination is centralcyanosis and clubbing, as well as evidence of pulmonaryhypertension If Eisenmenger’s syndrome is due to a patent ductusarteriosus, cyanosis and clubbing will be limited to the lowerextremities (“differential cyanosis”) Signs of pulmonary hypertensioninclude prominent “a” wave in the jugular venous pulse, a parasternallift due to right ventricular pressure overload, a prominent (and oftenpalpable) P2, and murmurs of tricuspid and pulmonic regurgitation.Other murmurs are not present (for example, the classic murmurs of

a ventricular septal defect or patent ductus arteriosus are absent) The

chest x ray film demonstrates dilatation of the central pulmonary

arteries with “pruning” of the distal vessels Cardiomegaly is notusually seen The electrocardiogram shows right axis deviation, rightatrial overload, and right ventricular hypertrophy

Echocardiography is useful in demonstrating a right ventricularpressure overload pattern, estimating the severity of pulmonaryhypertension, and demonstrating the underlying cardiac defect.Cardiac catheterization is extremely important in evaluating patientswith possible Eisenmenger’s syndrome In addition to demonstrating