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QUESTIONS 41-51: DETAILED CARDIAC ANSWERS

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QUESTION 41: PERICARDITIS

Etiology

• Infectious: Viral (Coxsackievirus B most common, ECHO, Adenovirus, HIV, EBV, CMR, SARS-CoV-2); Bacterial (TB is the most common identifiable infectious cause worldwide; Staph, Strep, H. flu); Fungal (Histoplasma, Candida); Parasitic
• Immune/Inflammatory: SLE (pericarditis in 40-80% at autopsy), RA (1-2% clinically), systemic sclerosis, sarcoidosis, Dressler syndrome (post-MI), post-pericardiotomy syndrome
• Metabolic: Uremia (pericarditis in up to 20% of patients with advanced CKD), hypothyroidism
• Neoplastic: Direct invasion (lung, breast cancer, lymphoma) or metastatic; malignant effusions have ~75% subsequent mortality
• Iatrogenic/Trauma: Post-cardiac surgery, radiation-induced, blunt chest trauma, esophageal perforation
• Drug-induced: Procainamide, hydralazine, isoniazid (lupus-like syndrome); immune checkpoint inhibitors (ipilimumab, pembrolizumab)

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Pathogenesis

1. Acute (<6 weeks): fibrinous or effusive
2. Subacute (6 weeks - 6 months): constrictive-effusive
3. Chronic (>6 months): effusive or constrictive
4. Recurrent: relapse after symptom-free period of at least 4-6 weeks

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Clinical Picture by Type

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Diagnosis

Inspection

• Patient characteristically leans forward to relieve pain
• Diaphoresis if febrile
• Tachypnea
• In large effusion: muffled heart sounds, distended neck veins, hypotension (Beck's triad in tamponade)

Palpation

• Precordial tenderness
• In effusion: displaced apical impulse becomes impalpable
• In constrictive pericarditis: palpable pericardial knock
• Check for subcutaneous edema (in constrictive/chronic)

Percussion

• In large effusion: cardiac dullness extends beyond apical impulse
• Ewart's sign: dullness at left scapular angle due to left lower lobe compression by large pericardial effusion (also called Pins sign)
• Hepatomegaly and ascites in constrictive pericarditis

Auscultation

• Pericardial friction rub: pathognomonic - scratchy, leathery sound, heard best at lower left sternal border with patient leaning forward and breath held in expiration
• Three components: atrial systole, ventricular systole, early ventricular diastole (systolic component is most consistent)
• May be evanescent - reassess frequently
• S3 may be heard in effusion
• In constrictive pericarditis: early diastolic pericardial knock (heard earlier and higher pitched than S3)

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Laboratory

• CBC: leukocytosis (bacterial, viral), eosinophilia (drug-induced)
• ESR/CRP/CRP: elevated in active inflammation - CRP is useful to guide duration of therapy
• Troponin I/T: may be elevated - indicates concomitant myocarditis (myopericarditis)
• BUN/creatinine: to exclude uremia as cause
• ANA, RF, anti-dsDNA: if SLE or RA suspected
• TSH/T4: if hypothyroidism suspected (asymptomatic effusion)
• HIV test: if risk factors present
• Blood cultures: if febrile
• Tuberculin skin test (PPD): in all patients (plus control)
• ASO titer: in children/teenagers (rheumatic fever)
• Pericardial fluid analysis (if pericardiocentesis performed): LDH, protein, cell count, cytology, cultures (bacterial, TB), PCR for TB, adenosine deaminase (elevated in TB)

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Instrumental Diagnostics

• Stage 1 (days 1-2): Diffuse ST elevation (concave/saddle-shaped) in all leads except aVR and V1; PR segment depression (highly specific)
• Stage 2 (1-3 weeks): ST returns to baseline, PR remains depressed
• Stage 3: T-wave inversion (after ST normalizes - differs from MI)
• Stage 4: ECG normalization
• Key differentiator from STEMI: changes are diffuse (not localized), concave elevation, no reciprocal changes except in aVR/V1

• Normal in acute fibrinous pericarditis
• "Water bottle" heart (globular cardiac silhouette) when effusion >250 mL
• "3 sign" and rib notching in coarctation (different entity)
• Calcification in chronic constrictive pericarditis

• Detects effusion (most sensitive method), quantifies size
• Tamponade signs: RV diastolic collapse, RA collapse, plethoric IVC, respiratory variation in mitral/tricuspid inflow
• Pericardial thickening in constrictive disease
• LV/RV function assessment

• CT: excellent for detecting pericardial calcification (constrictive), pericardial thickening
• Cardiac MRI (CMR): gold standard for pericardial inflammation - shows late gadolinium enhancement of inflamed pericardium; detects myocardial involvement

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Treatment (taking into account etiological factors)

• Activity restriction until symptoms/CRP normalize (Class I recommendation)
• Avoid anticoagulants (risk of hemopericardium) - unless AF or prosthetic valve requires it

• Aspirin 650 mg q6h OR Ibuprofen 300-800 mg q6-8h for 3-4 weeks, then taper
• Colchicine 0.5 mg twice daily (or 0.5 mg once daily if weight <70 kg) for 3 months - reduces recurrence from 55% to 24% at 18 months; reduces persistent symptoms at 72 hours
• Proton pump inhibitor (omeprazole 20 mg/day) to protect GI mucosa

• Reload colchicine + IM ketorolac 15-30 mg once, then oral NSAID + colchicine for at least 3 months
• Corticosteroids (prednisone 0.25-0.5 mg/kg/day) only if NSAIDs/colchicine contraindicated or failed - use low dose and slow taper to minimize recurrence risk
• Anakinra (IL-1 receptor antagonist) for refractory/steroid-dependent cases

• Bacterial/purulent: IV antibiotics (gram+ coverage: vancomycin + beta-lactam) + urgent surgical drainage - medical therapy alone has >30% mortality
• TB pericarditis: 4-drug anti-TB regimen (HRZE) for 6 months + prednisolone 60 mg/day tapered over 11 weeks to prevent constriction
• Uremic pericarditis: Intensified hemodialysis is treatment of choice; NSAIDs if not on dialysis; steroids if unresponsive
• SLE/RA: NSAIDs or hydroxychloroquine; corticosteroids for refractory cases; treat underlying disease
• Malignant effusion: Pericardiocentesis + chemotherapy/radiation of underlying malignancy; pericardial window for recurrent effusions
• Post-MI (Dressler syndrome): Aspirin preferred; avoid NSAIDs/corticosteroids as they impair myocardial healing

1. Constrictive pericarditis (definitive treatment - removes both layers)
2. Recurrent pericarditis refractory to medical therapy (>3 recurrences despite optimal medical management)
3. Purulent pericarditis with inadequate drainage
4. Large organized/multiloculated effusions not amenable to pericardiocentesis
5. Pericardial biopsy required for diagnosis

• Mortality of pericardiectomy: 5-15%; incomplete resection reduces efficacy

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QUESTION 42: CARDIAC TAMPONADE

Reasons for Development

• Neoplastic (most common in developed countries): lung, breast cancer, lymphoma, leukemia
• Idiopathic/viral pericarditis: acute viral pericarditis
• Iatrogenic: cardiac catheterization, pacemaker lead perforation, cardiac surgery, central line placement
• Trauma: penetrating or blunt thoracic injury, aortic dissection
• Uremia
• Radiation therapy
• TB (especially in developing world)
• Bacterial (purulent) pericarditis: most dangerous (high mortality)
• Anticoagulant therapy/hemopericardium

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Clinical Symptoms

• Dyspnea (most common symptom)
• Chest pain or pressure
• Anxiety and a sense of impending doom
• Fatigue and weakness
• Palpitations
• Dizziness, presyncope

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Physical Examination - Diagnosis

Inspection

• Obvious respiratory distress, tachypnea
• Tachycardia
• Pallor, diaphoresis (from low cardiac output)
• Distended neck veins (JVD) - elevated JVP
• Cyanosis in severe cases
• Pulsus paradoxus: inspiratory drop in systolic BP >10 mmHg (normally <10 mmHg)

Palpation

• Tachycardia (compensatory to maintain CO)
• Weak, thready peripheral pulses
• Hypotension (late sign)
• Apical impulse may be impalpable

Percussion

• Cardiac dullness extending beyond the apical impulse (large effusion)
• May detect hepatomegaly and ascites if longstanding

Auscultation

• Muffled/distant heart sounds - due to fluid insulating the heart
• Friction rub may be present (if pericarditis is the cause)
• Decreased breath sounds at left base (Ewart sign - lung compression)
• Hypotension with tachycardia - key hemodynamic finding

1. Hypotension
2. Elevated JVP (distended neck veins)
3. Muffled heart sounds

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Hemodynamics

• Increased intrapericardial pressure compresses all chambers
• RV compressed first during diastole (lower pressure chamber)
• LV filling progressively reduced
• Decreased stroke volume
• Compensatory tachycardia (catecholamine surge)
• Increased venous pressure (elevated JVP, hepatojugular reflux)
• Pulsus paradoxus (>10 mmHg drop in SBP on inspiration): exaggerated ventricular interdependence - RV expands during inspiration at expense of LV
• Progressive: CO falls → hypotension → cardiogenic shock → cardiac arrest

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Instrumental Criteria

• Sinus tachycardia (most common and often earliest finding)
• Electrical alternans: alternating QRS amplitude/axis due to heart swinging in effusion - highly specific for tamponade when combined with sinus tachycardia
• Low voltage QRS complexes
• ST changes of underlying pericarditis may be present

• "Water bottle" cardiac silhouette (globular enlargement of cardiac shadow)
• Clear lung fields (no pulmonary edema - distinguishes from heart failure)
• Lateral view: fat pad sign (separation of pericardial and epicardial fat stripes)

• Large pericardial effusion visualized
• RV diastolic collapse (earliest echocardiographic sign)
• RA systolic collapse (>1/3 of cardiac cycle = highly specific)
• Plethoric IVC (>2.1 cm, <50% respiratory collapse)
• Respiratory variation in mitral inflow: >25% variation (normal <10%)
• Tricuspid inflow variation >40%
• "Swinging heart" motion within effusion

• Equalization of intracardiac diastolic pressures (RA = RV diastolic = PCWP within 5 mmHg)
• Elevated RA pressure with prominent x descent but absent y descent (distinguishes from constrictive pericarditis which has both x and y descents)

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Methods of Treatment

• IV fluid bolus (500 mL NS) as temporizing measure to increase preload - particularly useful in hypovolemic tamponade
• Avoid mechanical ventilation if possible - positive intrathoracic pressure further reduces cardiac filling and may precipitate cardiovascular collapse
• Inotropes generally ineffective (maximal endogenous catecholamine stimulation already present)
• Avoid sedatives/anesthetics that blunt sympathetic response

• Echocardiography-guided percutaneous pericardiocentesis is preferred
• Indicated when ≥1 cm of fluid anterior to RV free wall throughout diastole
• Approach: subxiphoid (most common) or apical depending on echo guidance
• Needle entry site: defined by echocardiography as minimal distance from skin to fluid without intervening structures
• Insert needle → aspirate fluid → place guidewire → dilate → indwelling catheter for continued drainage (minimizes recurrence)
• Pericardial fluid analysis: LDH, protein, cell count, cytology, cultures, PCR for TB

• Hemodynamically significant effusions < 1 cm, organized, multiloculated, or focal (not amenable to percutaneous drainage)
• Recurrent effusions requiring pericardial window
• Bacterial/purulent pericarditis (urgent surgical drainage)
• Hemorrhagic effusions from trauma or aortic dissection - emergency surgery
• Need for pericardial tissue for diagnosis
• Pericardial window creation: allows drainage into pleural space, prevents recurrence - either surgical or percutaneous balloon creation
• Malignant effusions: balloon pericardiotomy or surgical window preferred as they recur

• Colchicine + NSAIDs to prevent recurrence
• Address underlying etiology (e.g., chemotherapy for malignancy, anti-TB therapy, dialysis for uremia)
• Prognosis: in-hospital mortality <10% with tamponade; subsequent mortality ~75% with malignant effusion vs 3-5% annual mortality for other causes

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QUESTION 43: MYOCARDITIS - Definition, Etiology, Pathogenesis, Classification, Clinical Picture, Variants

Definition

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Etiology

• Viral (most common in Western world): Coxsackievirus B (most common), SARS-CoV-2, HIV, Adenovirus, Echovirus, Parvovirus B19, CMV, EBV, Influenza, Hepatitis C, Herpes simplex, Varicella-zoster, measles, mumps, rubella, dengue, rabies, RSV
• Protozoal: Trypanosoma cruzi (Chagas - most common worldwide!), Toxoplasma gondii
• Bacterial: Corynebacterium diphtheriae (toxin-mediated), Borrelia burgdorferi (Lyme), Brucella, Salmonella, Mycobacterium, Neisseria meningitidis, Staphylococcus, Streptococcus
• Spirochetal: Treponema pallidum, Leptospira
• Rickettsial: Coxiella burnetii, Rickettsia rickettsii
• Fungal: Aspergillus, Candida, Cryptococcus, Histoplasma
• Parasitic: Trichinella spiralis, Echinococcus

• Heart transplant rejection (alloantigens)
• Autoimmune: Giant cell myocarditis, SLE, Kawasaki disease, sarcoidosis, eosinophilic granulomatosis with polyangiitis, celiac disease, polymyositis, scleroderma, Whipple disease

• Drugs: Anthracyclines, catecholamines, cocaine, amphetamines, cyclophosphamide, 5-fluorouracil, trastuzumab, interferon, immune checkpoint inhibitors (ipilimumab, pembrolizumab - increasingly important cause), clozapine, tricyclic antidepressants, thiazide diuretics
• Physical agents: Electric shock, radiation, hyperpyrexia
• Heavy metals: Copper, iron, lead
• Other: Arsenic, snake/scorpion bite, carbon monoxide, smallpox vaccination (7.8/100,000 administrations)

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Pathogenesis

1. Phase 1 - Direct viral injury (0-3 days): Cardiotropic viruses enter cardiomyocytes via receptor-mediated endocytosis (e.g., CAR receptor for Coxsackievirus). Viral genome is translated to produce viral proteins and proteases that directly damage cytoskeletal proteins. Coxsackievirus B3 protease 2A cleaves dystrophin, disrupting the cytoskeleton.
2. Phase 2 - Immune-mediated injury (3-14 days): Natural killer cells, macrophages, and T lymphocytes are recruited. Cytokine release (IL-1β, IL-6, TNF-α) amplifies inflammation. Molecular mimicry - viral antigens resembling cardiac proteins (myosin heavy chain, adenine nucleotide translocator) trigger autoreactive T-cell responses even after virus is cleared.
3. Phase 3 - Chronic autoimmune cardiomyopathy (>14 days): In susceptible individuals, autoimmune response persists leading to dilated cardiomyopathy with fibrosis, chamber dilation, and systolic dysfunction.

• Active myocarditis: myocyte degeneration/necrosis + cellular infiltrate ± fibrosis
• Borderline myocarditis: cellular infiltrate without myocyte injury
• Persistent myocarditis: continued active myocarditis on repeated biopsy
• Resolving/resolved myocarditis: diminished/absent infiltrate with connective tissue healing

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Classification

• Onset: Abrupt, within 2 weeks of viral prodrome
• Presentation: Severe hemodynamic compromise requiring mechanical circulatory support
• Histology: Multiple foci of active inflammation, myocyte necrosis
• LV: Normal or slightly dilated but hyperdynamic failure
• Prognosis: Paradoxically better long-term - if patient survives acute phase, typically complete recovery; ~93% survival at 11 years

• Onset: Less distinct, <3 months
• Presentation: Variable from mild symptoms to moderate HF
• LV: Dilated with impaired function
• Prognosis: ~56% recovery; ~44% progress to dilated cardiomyopathy or death

• Onset: Gradual >3 months
• Presentation: Progressive dilated cardiomyopathy picture
• May have persistent low-grade inflammation
• Histology: Giant cells, eosinophilic infiltrate (in autoimmune forms)

• Low-grade persistent inflammation despite clinical improvement
• Normal LV systolic function but diastolic dysfunction and persistent symptoms (chest pain, palpitations)

• Lymphocytic (most common)
• Eosinophilic
• Giant cell (most aggressive)
• Granulomatous (sarcoidosis-associated)
• Mixed

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Clinical Picture

• Chest pain (pleuritic or angina-like) - may mimic MI
• Dyspnea at rest or on exertion
• Palpitations and arrhythmias
• Fatigue, weakness
• Prodromal flu-like illness: fever, myalgias, upper respiratory or GI symptoms 1-4 weeks before
• Sudden cardiac death in young athletes (first presentation in some)

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Physical Examination

Inspection

• Tachycardia (most common physical finding)
• Signs of heart failure: orthopnea, diaphoresis
• Pallor, peripheral cyanosis in advanced disease
• Periorbital or pedal edema

Palpation

• Displaced, diffuse apical impulse (dilated cardiomyopathy)
• Signs of right heart failure: hepatomegaly, ascites, peripheral edema
• Weak peripheral pulses in cardiogenic shock

Percussion

• Increased area of cardiac dullness (cardiomegaly)
• Hepatomegaly

Auscultation

• S3 gallop (ventricular dysfunction, volume overload)
• S4 (reduced compliance)
• Mitral regurgitation murmur (annular dilation, papillary muscle dysfunction)
• Rubs may be present if myopericarditis
• Pulmonary rales (pulmonary edema in severe cases)
• Signs of tricuspid regurgitation in right HF

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Laboratory

• CBC: leukocytosis (viral prodrome), eosinophilia (drug/parasitic), anemia (chronic)
• ESR, CRP: elevated
• Troponin T or I: elevated in 30-50% of cases - marker of myocyte necrosis
• BNP/NT-proBNP: elevated (HF marker)
• CK-MB: may be elevated
• Viral serologies: paired acute and convalescent titers (coxsackievirus, adenovirus, influenza) - 4-fold rise is significant; correlation with biopsy best for HIV and Lyme
• ANA, anti-dsDNA: if autoimmune suspected
• Autoantibodies: against myosin heavy chain, adenine nucleotide translocator - biomarkers of autoimmune myocarditis
• Blood cultures: if bacterial sepsis
• Lyme serology (anti-Borrelia antibodies)
• TSH: hypothyroid cardiomyopathy
• Novel biomarker: microRNA has-miR-Chr8:96 - specific for myocarditis (rarely elevated in MI)

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Instrumental Diagnostics

• Sinus tachycardia (most common)
• Non-specific ST-T changes
• Bundle branch block (conduction system involvement)
• AV block (especially Lyme carditis - all degrees of AV block)
• Ventricular arrhythmias (VT, VF) especially in giant cell myocarditis
• Low voltage QRS complexes
• Q waves mimicking MI (focal myocarditis)

• Cardiomegaly (dilated heart)
• Pulmonary venous congestion/pulmonary edema
• Pleural effusions

• LV or RV systolic dysfunction, reduced EF
• Regional wall motion abnormalities (may mimic MI)
• LV dilation
• RV involvement (poor prognostic sign)
• LV thrombus (risk of embolism)
• Pericardial effusion (myopericarditis)
• Diastolic dysfunction
• MR or TR from ventricular dilation

• T2-weighted imaging: myocardial edema (signal intensity ratio myocardium:skeletal muscle >2)
• T1 early gadolinium enhancement: hyperemia and capillary leak
• T1 late gadolinium enhancement (LGE): fibrosis/necrosis - typically non-ischemic pattern (subepicardial or midwall), sparing subendocardium (unlike MI which is subendocardial)
• Lake Louise Criteria: 2 of 3 positive criteria = myocarditis likely: (1) T2 edema, (2) early gadolinium enhancement, (3) LGE
• CMR can show extent of pericardial involvement in myopericarditis

• Right ventricular EMB via jugular or femoral vein approach
• Dallas criteria applied to sample
• Immunohistochemistry: CD3 (T-cells) ≥7/mm², CD68 (macrophages)
• PCR on biopsy: viral genome detection (guides antiviral therapy)
• Indications (American/European guidelines):
  • New-onset HF with hemodynamic compromise (fulminant myocarditis)
  • New-onset HF with heart block or ventricular arrhythmias
  • Suspected giant cell myocarditis (rapidly progressive HF + arrhythmias)
  • HF refractory to standard therapy
  • Suspected systemic disease (sarcoidosis, hemochromatosis, amyloidosis)
• Limitations: sampling error (patchy distribution), Dallas criteria sensitivity 10-20%

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Complications

• Dilated cardiomyopathy (most significant long-term complication)
• Sudden cardiac death (ventricular arrhythmias)
• Heart failure (acute and chronic)
• Complete heart block requiring pacemaker
• Thromboembolic events (LV thrombus → stroke/peripheral embolism)
• Constrictive pericarditis (if myopericarditis)

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Basic Principles of Treatment

• Activity restriction: avoid strenuous exercise for at least 6 months after diagnosis (regardless of symptoms) - risk of sudden death is increased
• Treat underlying cause (antiviral, antibiotics for bacterial, anti-parasitic for Chagas, stop offending drug)

• ACE inhibitors (e.g., enalapril, lisinopril): reduce preload/afterload, prevent LV remodeling
• Beta-blockers (e.g., carvedilol, metoprolol succinate): after hemodynamic stabilization; reduce mortality, arrhythmia risk
• Diuretics: loop diuretics (furosemide) for fluid overload
• Aldosterone antagonists (spironolactone/eplerenone): if EF ≤35%
• Digoxin: use with caution (may worsen myocarditis by increasing cytokine production) - reserve for AF rate control or severe systolic dysfunction refractory to other therapy
• SGLT2 inhibitors (dapagliflozin/empagliflozin): now part of HF with reduced EF management

• Antiarrhythmic drugs for sustained VT
• Temporary pacing for high-degree AV block (especially Lyme carditis - usually reversible)
• ICD: defer implantation for ≥6 months to allow recovery; permanent ICD if sustained arrhythmia persists

• IABP (intra-aortic balloon pump), ECMO, Impella, or LVAD for fulminant myocarditis with cardiogenic shock
• Bridge to recovery or transplantation

• Not recommended for viral myocarditis (may worsen by impairing viral clearance)
• Indicated for: giant cell myocarditis (cyclosporine + corticosteroids + azathioprine), autoimmune/lymphocytic myocarditis with positive biopsy (but negative viral PCR), cardiac sarcoidosis (prednisone), Lyme carditis after antibiotics
• Colchicine and NSAIDs: for myopericarditis component (pericardial involvement)
• IVIG: used in pediatric myocarditis and acute dilated cardiomyopathy in some centers

• Vaccination (influenza, COVID-19 - note mRNA vaccine myocarditis is rare and usually self-limited)
• Avoiding alcohol, illicit drugs, cardiotoxic medications
• Genetic counseling and family screening for inherited cardiomyopathies

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QUESTION 44: MYOCARDITIS - MAYO CLINIC CLASSIFICATION

1. Lymphocytic Myocarditis (most common, ~50%)

• Predominantly lymphocytic infiltrate (CD4+ and CD8+ T cells)
• Usually viral etiology
• Most respond to GDMT; some progress to DCM

2. Eosinophilic Myocarditis (~2-5%)

• Eosinophilic infiltrate; two subtypes:
  • Hypersensitivity myocarditis: drug reaction (antibiotics, diuretics, anticonvulsants); typically mild
  • Acute necrotizing eosinophilic myocarditis: rare, rapid hemodynamic collapse, requires emergency immunosuppression
• Peripheral eosinophilia often present
• Treatment: remove offending agent; corticosteroids

3. Giant Cell Myocarditis (~10-20% of biopsy-positive cases)

• Most aggressive form - highest mortality
• Multi-nucleated giant cells + extensive necrosis
• No identifiable viral cause; autoimmune pathogenesis
• Clinical features: rapid-onset HF, ventricular tachycardia, AV block in young adults
• Treatment: triple immunosuppression (cyclosporine + corticosteroids + azathioprine) - improves transplant-free survival from 3 to 12.3 months
• High rate of relapse after transplantation (recurrence in 25%)

4. Granulomatous Myocarditis (Cardiac Sarcoidosis)

• Non-caseating granulomas with multinucleated giant cells
• Associated with systemic sarcoidosis or isolated cardiac sarcoidosis
• Clinical: AV block (complete heart block is hallmark), VT, HF, sudden death
• ECG: right bundle branch block pattern is common
• Diagnosis: PET scan (FDG-avid myocardial inflammation), CMR
• Treatment: corticosteroids (prednisone 40 mg/day tapered), ICD implantation for VT/sudden death risk

5. Chagas Myocarditis (Infectious - special form)

• Trypanosoma cruzi - most common worldwide cause of myocarditis
• Phases: acute (myocarditis), indeterminate (latent), chronic (DCM, apical aneurysm, arrhythmias)
• Pathognomonic: apical LV aneurysm on echo
• Treatment: Benznidazole or nifurtimox (anti-parasitic - effective mainly in acute phase)

6. Peripartum Myocarditis

• Occurs in last month of pregnancy or within 5 months postpartum
• Autoimmune component; PRLACT16kD cleavage product implicated
• Treatment: bromocriptine (to inhibit prolactin), GDMT

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Diagnosis - Instrumental and Laboratory Role (Mayo Clinic approach)

• CMR as preferred initial test before biopsy
• EMB reserved for specific indications (fulminant, arrhythmic, suspected giant cell)
• Diagnostic algorithm: echo → CMR → EMB if high-risk features

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Basic Principles of Treatment (same as Q43, see above)

• Influenza vaccination
• Avoid alcohol, recreational drugs
• No strenuous exercise during acute phase (6 months minimum)
• Family screening if genetic/familial cardiomyopathy component

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QUESTION 45: CONGENITAL HEART DISEASE IN ADULTS

Etiology

• Down syndrome (trisomy 21): 50% have endocardial cushion defects (AV canal), VSD
• Trisomy 13 and 18: VSD in 90%
• Turner syndrome (45,X): coarctation of aorta, bicuspid aortic valve, ASD
• 22q11 deletion (DiGeorge/CATCH-22 syndrome): Tetralogy of Fallot (15% have 22q11 deletion), truncus arteriosus, interrupted aortic arch; phenotype = Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia
• Noonan syndrome: pulmonary stenosis, hypertrophic cardiomyopathy
• Williams syndrome: supravalvular aortic stenosis, pulmonary artery stenosis
• Marfan syndrome: aortic root dilation, MR, MVP

• Rubella (1st trimester): PDA (most characteristic), pulmonary artery stenosis, ASD, VSD - "Rubella syndrome"
• CMV, Toxoplasmosis: non-specific CHD
• Coxsackievirus: transient neonatal cardiomyopathy

• Warfarin: pulmonary stenosis, PDA
• Lithium: Ebstein anomaly (tricuspid valve downward displacement)
• Phenytoin, valproate: various CHD
• Thalidomide: cardiac and limb defects
• Alcohol (fetal alcohol syndrome): VSD, ASD, Tetralogy

• Maternal diabetes (poorly controlled): transposition of great arteries, VSD, HCM
• Maternal SLE: complete heart block in neonate (anti-Ro antibodies)
• Maternal phenylketonuria: VSD, Tetralogy

• Hypoxia at high altitude
• Organic solvents
• Ionizing radiation

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Classification by Complexity

• Small isolated VSD, ASD, PDA (spontaneous closure common)
• Isolated pulmonary stenosis (mild)
• Bicuspid aortic valve

• Large VSD, large ASD, AV canal (complete)
• Moderate pulmonary stenosis
• Coarctation of aorta (isolated)
• Partial anomalous pulmonary venous drainage
• Ebstein anomaly (mild)

• Tetralogy of Fallot
• Transposition of the great arteries
• Tricuspid atresia
• Pulmonary atresia
• Total anomalous pulmonary venous return
• Double-outlet right ventricle
• Univentricular heart (single ventricle)
• Eisenmenger syndrome

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Hemodynamic Disorders and Options

• ↑ pulmonary blood flow, volume overload of right heart, pulmonary hypertension
• Examples: ASD, VSD, PDA
• Natural history: gradual Eisenmenger syndrome (irreversible pulmonary hypertension with shunt reversal)

• Pressure overload of affected ventricle
• Examples: Aortic stenosis, pulmonary stenosis, coarctation
• May lead to ventricular hypertrophy, heart failure, arrhythmias

• ↓ pulmonary blood flow, systemic hypoxemia, polycythemia, clubbing
• Examples: Tetralogy of Fallot (post-repair adults), Eisenmenger syndrome

• Volume overload
• Most common post-surgical: pulmonary regurgitation after TOF repair, residual VSD

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Clinical Features

• Cyanosis: central (lips, tongue) vs. peripheral; differential cyanosis (feet > hands = PDA with Eisenmenger)
• Clubbing: chronic hypoxemia >6 months
• Polycythemia: compensatory; causes hyperviscosity, thrombosis
• Exercise intolerance: common across many CHDs
• Arrhythmias: very common in adults with repaired CHD (especially AF/flutter in ASD, VT/VF post-TOF repair)
• Endocarditis: all unrepaired CHD (except isolated ASD secundum) - SBE prophylaxis guidelines apply
• Paradoxical emboli: right-to-left shunts → systemic embolism (stroke, abscess)

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Diagnostic Methods

• ECG: axis, hypertrophy patterns, arrhythmias, bundle branch blocks
• Chest X-ray: cardiac size, pulmonary vascularity (plethora = shunt, oligemia = obstruction), cardiac silhouette shape
• Transthoracic echocardiography (TTE): first-line imaging - identifies anatomy, function, shunts, pressures (Doppler)
• Transesophageal echocardiography (TEE): superior for ASD, venous anomalies, prosthetic valves
• Cardiac MRI: gold standard for complex anatomy, RV function, quantification of shunts, regurgitant volumes
• Cardiac CT: coronary anatomy, vascular anomalies, calcification
• Cardiac catheterization: measures pulmonary vascular resistance (critical before closure), PA pressures, Qp:Qs (shunt ratio), angiography

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Principles of Treatment

• Specialized adult congenital heart disease (ACHD) centers
• Medical management: heart failure therapy, anticoagulation, arrhythmia management
• Percutaneous interventions: device closure (ASD, PDA, VSD), balloon valvuloplasty (pulmonary stenosis), stenting (coarctation)
• Surgical repair/re-operation
• Heart transplantation for end-stage disease
• SBE prophylaxis per current guidelines (high-risk procedures + high-risk lesions)
• Contraception counseling (pregnancy risk stratification)
• Exercise restrictions based on specific lesion and repair status

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QUESTION 46: PATENT DUCTUS ARTERIOSUS (PDA)

Etiology

• Familial recurrence rate ~3%
• Associated with chromosome 12q24 mutations
• Part of Char syndrome (mutations in TFAP2B gene): facial dysmorphism, hand anomalies, PDA
• Associated with Down syndrome, Turner syndrome, DiGeorge syndrome

• Congenital rubella (1st trimester): PDA is the most characteristic cardiac lesion of rubella syndrome - rubella virus directly inhibits ductal smooth muscle contraction
• Other maternal infections (CMV) may contribute

• Prematurity (prostaglandin E2 and E1 levels high, oxygen tension low - both promote ductal patency)
• Birth at high altitude (chronic hypoxia)
• Female sex (PDA 2-3x more common in females)
• Respiratory distress syndrome in preterm infants

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Pathophysiology

• Aortic pressure > pulmonary artery pressure → left-to-right shunt (aorta → PA)
• Continuous flow throughout cardiac cycle
• Left atrium and LV dilate (volume overload)
• Increased pulmonary blood flow → pulmonary hypertension → eventually Eisenmenger (R→L shunt) in 5%
• RV progressively affected as pulmonary hypertension develops

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Diagnosis

Inspection

• Differential cyanosis (with Eisenmenger): toes cyanotic and clubbed, fingers normal - because R→L shunt from PA enters descending aorta distal to subclavian artery
• Signs of heart failure in large PDA: tachypnea, diaphoresis, poor feeding in infants; exercise intolerance in adults
• Growth retardation in children with large PDAs

Palpation

• Bounding (waterhammer) pulse - wide pulse pressure (aortic diastolic runoff into PA lowers DBP)
• Left and right ventricular heaves depending on relative volume/pressure overload
• Thrill at left upper sternal border/infraclavicular area
• Hepatomegaly (right heart failure)

Percussion

• Increased cardiac dullness (cardiomegaly)
• Hepatomegaly on abdominal percussion

Auscultation

• Classic "machinery" murmur (Gibson murmur): continuous, crescendo-decrescendo ("rolling thunder"), heard best at first or second left intercostal space below left clavicle - pathognomonic
• As pulmonary pressure rises: diastolic component shortens progressively
• With Eisenmenger physiology: murmur disappears; findings dominated by pulmonary hypertension (loud P2, Graham Steell murmur of PR)
• With large shunt: apical mid-diastolic flow rumble (increased mitral flow)
• Bounding heart sounds

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Laboratory

• CBC: polycythemia in Eisenmenger physiology; anemia from iron deficiency in large left-to-right shunts
• Pulse oximetry: differential oxygen saturation (toes < fingers in Eisenmenger)
• BNP: elevated in HF
• No specific blood tests diagnostic of PDA itself

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Instrumental

• Small PDA: normal
• Moderate PDA: LV hypertrophy and dilation (left axis deviation, tall R in V5-6)
• Large PDA with PH: biventricular hypertrophy
• Eisenmenger: RV hypertrophy, right axis deviation

• Small PDA: normal
• Moderate/large PDA:
  • Pulmonary plethora (increased vascular markings)
  • Dilated ascending aorta and pulmonary artery
  • Enlarged left atrium and left ventricle
  • In older patients: calcification at the PDA location
• Eisenmenger: peripheral pruning of pulmonary vessels

• May not directly visualize PDA but:
• Color Doppler: continuous turbulent flow in MPA adjacent to bifurcation - diagnostic
• LA and LV dilation (volume overload)
• PA pressure estimation (tricuspid regurgitation jet)
• LA:aorta ratio >1.5:1 indicates significant shunt
• Visualize PDA by parasternal short axis view

• Oxygen step-up at PA level (increased O2 saturation)
• PA pressure measurement
• Pulmonary vascular resistance (PVR) - mandatory before closure if PH present
• Aortography: delineates PDA anatomy, size
• Calculate Qp:Qs (shunt ratio) - significant if >1.5:1

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Treatment

• Ibuprofen or indomethacin (prostaglandin inhibitors): effective for closure in premature infants; NOT effective in term infants or adults (fully developed fibromuscular duct)
• Heart failure management: diuretics, ACE inhibitors (for symptomatic large PDAs)
• SBE prophylaxis for unrepaired PDA during at-risk procedures

• Percutaneous transcatheter closure: preferred for most PDAs in adults and older children
  • Coil embolization: for small PDAs (<3 mm)
  • Amplatzer duct occluder: for moderate to large PDAs
  • Advantages: avoids sternotomy, short hospital stay
  • Reported mortality <1%
• Surgical ligation (PDA ligation): for premature infants, large calcified PDAs, complex anatomy not suitable for device, or if endarteritis has occurred
  • Thoracoscopic video-assisted approach for infants
  • Open thoracotomy for complex cases
  • Operative mortality <1-8% depending on calcification and PH

• Left-sided heart enlargement (LA, LV dilation) due to significant shunt
• Prior infectious endarteritis
• Symptomatic PDA at any size
• Pulmonary hypertension if still reversible (PVR <2/3 systemic vascular resistance)

• Eisenmenger syndrome (irreversible pulmonary hypertension with R→L shunt) - closure worsens symptoms, increases mortality
• PDA providing pulmonary blood flow in pulmonary atresia (prostaglandin E1 to keep open)

• After successful closure in infancy/childhood: normal cardiac function, no special follow-up
• 2/3 of untreated patients die by age 60; mortality 3-4%/year by 4th decade

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QUESTION 47: ATRIAL SEPTAL DEFECT (ASD)

Etiology

• Autosomal dominant mutations in NKX2.5 (transcription factor critical for cardiac morphogenesis): causes ASD + AV conduction defects
• GATA4 mutations: familial ASD
• TBX5 mutations: Holt-Oram syndrome (ASD + hand anomalies)
• Familial ASD: ~5-10% recurrence in first-degree relatives

• Rubella: ASD is a known cardiac manifestation of rubella embryopathy
• Other maternal viral infections (early 1st trimester) during cardiac septation (3rd-7th week) can cause ASD

• Primary (ostium primum): failure of septum primum to fuse with endocardial cushions; associated with cleft mitral valve, MR, AV block, Down syndrome
• Secondary (ostium secundum): failure of septum secundum to cover fossa ovalis; most common type; isolated lesion

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Pathophysiology

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Diagnosis

Inspection

• Most asymptomatic until 3rd-4th decade
• Initial symptoms: exercise intolerance, dyspnea on exertion, fatigue (right HF and PH)
• Palpitations (AF, flutter - very common after 4th decade due to RA dilation)
• Recurrent respiratory infections (increased pulmonary flow)
• Stroke (paradoxical embolism through ASD - even without Eisenmenger)
• Cyanosis only in Eisenmenger or with R→L shunting (e.g., during Valsalva)

Palpation

• Normal LV impulse (unless associated MV disease)
• RV impulse palpable at left parasternal area or subxiphoid (volume-loaded RV)
• Dilated pulmonary artery: palpable at 2nd left intercostal space
• No thrill (usually low-pressure L→R shunt)

Percussion

• Increased area of cardiac dullness (RA, RV dilation)

Auscultation

• Wide and fixed splitting of S2: hallmark of ASD
  • Fixed because: increased venous return during inspiration normally widens S2 splitting, but this is offset by decreased L→R shunt → net effect: constant splitting regardless of respiration
  • P2 delayed (RV overload + increased pulmonary vascular capacitance)
• Soft ejection systolic murmur at 2nd left intercostal space (increased pulmonary valve flow - not from ASD itself)
• Mid-diastolic murmur at lower left sternal border (increased tricuspid flow) if large shunt (Qp:Qs >2:1)
• With advanced PH: loud P2, Graham Steell murmur (pulmonary regurgitation), TR murmur
• Evidence of right heart failure: ↑ JVP with hepatojugular reflux, peripheral edema

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Laboratory

• CBC: generally normal; polycythemia in Eisenmenger
• Pulse oximetry: differential if Eisenmenger
• BNP/NT-proBNP: elevated with right HF
• ECG: incomplete right bundle branch block (rSR' in V1) - hallmark finding; right axis deviation; atrial abnormalities (P pulmonale), AF/flutter; prolonged PR interval
• In ostium primum: left axis deviation (common due to aberrant AV node)

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Instrumental

• Pulmonary vascular plethora (increased vascular markings bilaterally)
• Dilated main pulmonary artery and bilateral branches
• Right atrial and RV enlargement
• Small aortic knuckle
• With Eisenmenger: central pulmonary artery dilation but peripheral pruning

• Secundum and primum ASDs visualized with TTE; sinus venosus ASD may require TEE
• Doppler: L→R color flow across defect
• RV and RA dilation, RV volume overload (paradoxical septal motion)
• Estimate PA pressures
• LA:aorta ratio
• TEE + agitated saline (bubble study): R→L shunting with Valsalva = patent foramen ovale
• Shunt ratio Qp:Qs measured

• Precise measurement of RV/LV volumes, shunt quantification
• Superior for sinus venosus ASDs and anomalous pulmonary veins

• Oxygen step-up at RA level
• PA pressure, PVR measurement
• Shunt ratio

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Treatment and Indications for Surgical Treatment

• Right-sided heart enlargement (RA, RV dilation) with or without symptoms
• Qp:Qs ≥1.5:1
• Paradoxical embolism/cryptogenic stroke with documented R→L shunt
• Symptomatic patients with significant shunts even with PH if PVR <2/3 systemic

• Preferred for ostium secundum ASDs up to 3.5 cm diameter, with adequate septal rim
• Amplatzer septal occluder or similar device
• Avoids sternotomy and cardiopulmonary bypass
• Performed in cardiac catheterization lab

• Ostium primum ASD (requires repair of cleft mitral valve)
• Sinus venosus ASD (requires anomalous pulmonary vein reimplantation)
• Coronary sinus ASD
• Device closure not technically feasible (deficient rim, large size >3.5 cm)
• Concomitant valvular repair required

• Closure before age 25: normal survival
• Closure at age 40-60 with symptoms and significant shunt: improved functional status and survival
• Arrhythmias (AF/flutter) may persist even after closure if atria are dilated - require antiarrhythmic therapy

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QUESTION 48: VENTRICULAR SEPTAL DEFECT (VSD)

Etiology

• Autosomal dominant mutations: GATA4, NKX2.5, TBX5, CFC1 (heterotaxy)
• Familial recurrence rate: ~3%
• Associated chromosomal disorders: Down syndrome (trisomy 21), trisomy 13, trisomy 18 (90% have VSD)
• Part of 22q11 deletion syndromes

• Rubella (first trimester): VSD can be part of rubella embryopathy
• Influenza in first trimester: some association with VSD

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Classification

• Small (restrictive) VSD: Qp:Qs <1.5:1; no LV volume overload; PA pressure normal; Roger's disease
• Moderate VSD: Qp:Qs 1.5-2.0:1; mild LV dilation; mild-moderate PH
• Large (non-restrictive) VSD: Qp:Qs >2:1; LV dilation; equal PA and aortic pressure; Eisenmenger if untreated

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Clinical Forms

• Loud harsh holosystolic murmur but minimal hemodynamic consequences
• Near-normal pulmonary pressure
• No symptoms; incidental finding
• Risk: endocarditis (~0.45%/year)

• Dyspnea on exertion, recurrent respiratory infections
• LV dilation on echo
• Progressive PH risk

• Symptoms in infancy: poor feeding, tachypnea, failure to thrive
• Adults: dyspnea, cyanosis (if Eisenmenger develops)

• R→L shunting, central cyanosis, clubbing, polycythemia
• Murmur may disappear as shunt reverses

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Hemodynamics

• L→R shunt at ventricular level (systole primarily)
• Increased pulmonary blood flow → LA and LV volume overload → LV dilation
• Progressive pulmonary vascular disease → ↑ PVR → ↑ PA pressure → Eisenmenger complex
• High-velocity jet across VSD creates right ventricular pressure overload in some configurations

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Diagnosis

Inspection

• Small VSD: normal appearance, no cyanosis
• Large VSD: tachypnea, signs of HF, underdeveloped chest
• Eisenmenger: central cyanosis, clubbing, polycythemia, differential cyanosis

Palpation

• Systolic thrill at lower left sternal border (4th ICS) - pathognomonic of restrictive VSD
• Hyperdynamic LV apical impulse (volume-loaded LV)
• Right ventricular heave if PH develops
• Displaced apical impulse (LV dilation)
• Hepatomegaly in right HF

Percussion

• Increased cardiac dullness (biventricular enlargement)

Auscultation

• Holosystolic (pansystolic) murmur: best heard at lower left sternal border (4th ICS), harsh, grade 3-5/6 - classically louder murmur = smaller VSD (paradox of Roger's disease)
• Large VSD: softer murmur (less pressure gradient), loud P2 (PH)
• Apical mid-diastolic murmur: increased mitral flow if large L→R shunt (Qp:Qs >2:1)
• Outlet VSD: early diastolic murmur of AR (aortic cusp prolapse)
• Eisenmenger: murmur disappears, loud P2, Graham Steell (PR murmur)
• S3 if left HF
• Signs of right HF in advanced disease

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Differential Diagnosis

• Mitral regurgitation (both pansystolic, but MR heard at apex radiating to axilla)
• Tricuspid regurgitation (louder with inspiration - Carvallo sign)
• Hypertrophic obstructive cardiomyopathy
• Aortic stenosis (systolic, but ejection-type, at base)

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Laboratory

• CBC: polycythemia (Eisenmenger), anemia (large L→R shunts, iron deficiency)
• BNP elevated in HF
• ABG: hypoxemia in Eisenmenger

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Instrumental

• Small VSD: normal
• Moderate VSD: LV hypertrophy (tall R in V5-6, deep S in V1)
• Large VSD: biventricular hypertrophy
• PH developing: right axis deviation, RV hypertrophy
• Perimembranous VSD: may show LBBB or conduction defects (AV node proximity)

• Small VSD: normal
• Moderate/large VSD: cardiomegaly (LA, LV, and RA/RV enlargement), pulmonary plethora, dilated PA
• Eisenmenger: dilated central PA, peripheral vascular pruning

• Transthoracic echo: defines location, size, number of defects; LV/RV volumes; PA pressure (TR jet velocity)
• Color Doppler: L→R flow, velocity across VSD (high velocity = restrictive/small VSD)
• Measures Qp:Qs
• Watch for AR in outlet VSDs (aortic cusp prolapse)

• Oxygen step-up at RV level
• PA pressure and PVR measurement (critical for repair decision)
• Shunt ratio Qp:Qs
• Assess reversibility of PH (response to nitric oxide/oxygen)

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Treatment

• Small muscular and perimembranous VSDs: ~50-75% close spontaneously in first 2 years of life; watch-and-wait policy

• Diuretics, ACE inhibitors for heart failure
• SBE prophylaxis
• No closure is possible if Eisenmenger (contraindicated)
• Eisenmenger management: oxygen, oral anticoagulants, pulmonary vasodilators (sildenafil, bosentan), phlebotomy for severe polycythemia (>65% hematocrit)

• Muscular and perimembranous VSDs (selected cases)
• Amplatzer muscular VSD occluder
• Particularly useful for post-MI VSDs and high surgical risk patients
• Emerging technology: periventricular device closure

• Patch closure via cardiopulmonary bypass
• Indications:
  • Qp:Qs ≥2:1
  • Progressive LV dilation
  • Prior endocarditis
  • Outlet VSD with progressive AR
  • Perimembranous VSD (surgical preferred)
  • Inlet VSD requiring AV valve repair
  • Recurrent pneumonia despite medical therapy
• Mortality <1% in experienced centers (isolated VSD repair)
• Pulmonary artery banding (palliative): if surgery not immediately feasible in infants with severe PH

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QUESTION 49: AORTIC VALVE STENOSIS (Congenital, in Adults)

Anatomical Classification

• Bicuspid aortic valve (~2% of general population, most common congenital cardiac anomaly in adults): accounts for up to 50% of surgical aortic stenosis in adults; two leaflets (often asymmetric) with raphe; progressive calcification/stenosis typically manifests 4th-6th decade
• Unicuspid: presents in infancy/early childhood with severe stenosis
• Tricuspid (dysplastic): fibrous thickened leaflets; less common

• Discrete fibromuscular ring or tunnel below aortic valve
• Progressive LV outflow obstruction
• May damage aortic valve (secondary AR)

• Narrowing of ascending aorta above coronary ostia
• Associated with Williams syndrome (elastin gene mutation: ELN)
• Coronary arteries at risk (above obstruction - high pressure) → early atherosclerosis

• Stage A: Risk factors, no valve disease
• Stage B: Progressive AS (mild-moderate), no symptoms, EF preserved
• Stage C: Severe AS, asymptomatic (C1: preserved EF; C2: EF <50%)
• Stage D: Severe AS with symptoms

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Hemodynamics and Pathophysiology

• Obstruction to LV outflow → pressure overload → concentric LV hypertrophy (compensation)
• ↑ LV end-diastolic pressure → impaired LV relaxation → diastolic dysfunction
• Myocardial O2 demand increases (hypertrophy, ↑ wall stress) while supply decreases (low diastolic pressure, compression of subendocardial vessels) → angina without CAD
• As disease progresses: LV systolic dysfunction, pulmonary venous hypertension, HF
• Reduced forward stroke volume → syncope (especially on exertion - vasodilatation with fixed CO)
• Critical AS: AVA <1.0 cm² (normal 3-4 cm²); mean gradient >40 mmHg

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Diagnosis

Inspection

• Pallor (low cardiac output)
• Classic triad of symptoms (each heralding poor prognosis without intervention):
  1. Angina (survival ~5 years untreated)
  2. Syncope (survival ~3 years untreated)
  3. Heart failure/dyspnea (survival ~2 years untreated)

Palpation

• Sustained, heaving apex beat - pressure-loaded, non-displaced LV
• Parvus et tardus pulse - slow-rising, small-volume carotid pulse (plateau pulse): pathognomonic
• Systolic thrill at aortic area (2nd right ICS) and carotid arteries
• Narrow pulse pressure

Percussion

• Cardiac dullness at left sternal border (LV hypertrophy but not necessarily displaced)

Auscultation

• Ejection systolic murmur (ESM): harsh, crescendo-decrescendo, heard at 2nd right intercostal space (aortic area), radiates to carotid arteries (Gallavardin phenomenon - musical component to apex that mimics MR)
• Murmur peaks late in systole with severe AS (peak shifts later as severity ↑)
• Soft or absent A2 (calcified, immobile leaflets)
• S4 gallop (stiff, hypertrophied LV)
• Ejection click just before murmur (bicuspid valve - lost when valve calcifies)
• When LV fails: S3, displaced apex beat

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Laboratory

• CBC: normal or anemia exacerbating symptoms
• BNP/NT-proBNP: elevated with LV dysfunction; useful to monitor progression
• Troponin: elevated in severe AS with LV damage
• No pathognomonic blood tests

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Instrumental

• LV hypertrophy (Sokolow-Lyon: SV1 + RV5/6 > 35 mm)
• LV strain pattern (ST depression, T inversion in lateral leads)
• Left atrial abnormality (LAE)
• LBBB (advanced disease)

• Heart size initially normal or mildly enlarged (concentric hypertrophy - no dilation)
• Post-stenotic dilation of ascending aorta (hallmark)
• Calcification of aortic valve (best seen on lateral view)
• Pulmonary venous congestion when LV fails

• Aortic valve morphology (bicuspid, tricuspid, calcification)
• Valve area by planimetry or continuity equation
• Mean and peak gradients (Doppler)
• LV size, wall thickness, EF
• Staging: mean gradient >40 mmHg + AVA <1 cm² = severe AS
• Low-flow/low-gradient AS (EF <50%): use dobutamine stress echo to distinguish true severe from pseudo-severe
• Measure pulmonary pressures

• Aortic valve calcium score: Agatston score - score >1600 in men, >800 in women = severe AS
• Planning for TAVR: annular dimensions, access anatomy
• Detects subvalvular/supravalvular anatomy

• Hemodynamic assessment when echo inconclusive
• Pre-surgical coronary angiography (to determine need for CABG with AVR)
• Pullback gradient across AV

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Differential Diagnosis

• Hypertrophic obstructive cardiomyopathy (murmur ↑ with Valsalva/standing, ↓ with squatting)
• Pulmonary stenosis (murmur at 2nd left ICS, radiates to back)
• MR (pansystolic, apex to axilla)
• Aortic sclerosis (calcification without obstruction - AVA >1.5 cm², mean gradient <20 mmHg)
• Supravalvular AS (both arm pressures may differ; no ejection click; associated with Williams)

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Treatment

• Avoid vasodilators (can cause hypotension - reduce preload in stiff, non-compliant LV)
• Treat hypertension carefully (ACE inhibitors, calcium channel blockers in small doses)
• Statins: do NOT prevent progression (negative trials), but treat concomitant CAD
• Treat HF: diuretics for volume overload, beta-blockers if tachycardia, digoxin if AF
• Exercise restriction with severe symptomatic AS

• Class I (mandatory): Symptomatic severe AS (angina, syncope, HF) + AVA <1 cm²
• Class I: Severe AS undergoing other cardiac surgery (CABG, MV repair)
• Class IIa: Asymptomatic severe AS with EF <50% (Stage C2)
• Class IIa: Very severe AS (mean gradient >60 mmHg, velocity >5 m/s) even if asymptomatic
• Class IIb: Moderate AS with undergoing other cardiac surgery

• Preferred in younger patients (<65 years), bicuspid AV anatomy
• Bioprosthetic valve (less durable but no anticoagulation needed; re-replacement after 10-15 years)
• Mechanical valve (durable; lifelong warfarin required)
• Ross procedure (pulmonary autograft): in younger patients - own pulmonary valve moved to aortic position, RV outflow reconstructed with homograft

• Catheter-based valve implantation via transfemoral, transaortic, or transapical approach
• Initially for high surgical risk; now approved for intermediate and low surgical risk patients
• PARTNER 3 and Evolut Low Risk trials: TAVR non-inferior to surgery at 2 years for low-risk patients
• Valve-in-valve TAVR: for degenerated bioprosthetic valves

• Temporary palliative option (restenosis common within 6-12 months)
• Bridge to definitive AVR/TAVR
• Used for hemodynamically unstable patients, or non-cardiac surgery preparation

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QUESTION 50: COARCTATION OF THE AORTA

Etiology

• Turner syndrome (45,X): most common syndrome associated with coarctation (~35% of Turner patients have coarctation); also bicuspid AV, aortic stenosis, ASD
• Bicuspid aortic valve present in ~50% of coarctation patients
• Autosomal dominant familial recurrence
• 22q11 deletion: coarctation in some
• Loeys-Dietz and Williams syndromes occasionally associated

• Maternal rubella: coarctation can be part of rubella syndrome
• Same risk factors as other CHD

1. Postductal (adult type, most common): discrete shelf-like narrowing just distal to left subclavian artery origin; well-developed collaterals; presents later in life with hypertension
2. Preductal (infantile/ductal type, rare): proximal to ductus insertion; collaterals poorly developed; presents in infancy with heart failure and shock when ductus closes

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Clinical Presentation

Inspection

• Asymptomatic in many (incidental finding of hypertension or murmur)
• Headaches, epistaxis (upper body hypertension)
• Claudication, coldness, weakness of legs (lower body ischemia)
• Differential cyanosis (feet > hands) if preductal type with PDA open (deox blood from PA enters descending aorta)
• Growth retardation in severe cases

Palpation

• Brachial-femoral pulse delay (classic finding): femoral pulse delayed relative to radial/brachial pulse
• Diminished femoral pulses (reduced volume)
• Upper extremity hypertension with lower extremity normotension or hypotension
• Systolic BP in right arm 15-20 mmHg higher than legs: diagnostic (if right arm > left arm: obstruction proximal to left subclavian)
• Palpable collaterals in intercostal and subscapular areas

Percussion

• Hepatomegaly and cardiac enlargement (rare; depends on HF presence)

Auscultation

• Ejection systolic murmur at left sternal border and back (between scapulae) - over coarctation site
• Ejection click if bicuspid AV
• Continuous murmur from collateral vessels (intercostal, internal mammary arteries)
• If bicuspid AV stenosis: aortic ejection murmur at right upper sternal border
• Signs of AR if bicuspid AV incompetent (early diastolic murmur)
• "Machinery" or bruits heard at the back and intercostal spaces from collaterals

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Coarctation Options (Types)

• Discrete (simple) coarctation: localized shelf; most amenable to treatment
• Hypoplastic (tubular) coarctation: longer segment of narrowing; higher risk
• Coarctation with complex associated lesions: PDA, VSD, bicuspid AV, Shone syndrome (multiple LV obstructions)
• Recoarctation: recurrence after repair (more common after balloon angioplasty)

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Laboratory

• CBC: normal unless associated polycythemia/anemia
• Blood pressure (upper and lower extremities): most important "laboratory" measure
• BNP elevated if HF
• Creatinine: may be elevated if long-standing hypertension causes renal dysfunction
• Echo-Doppler: gradient across coarctation

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Instrumental

• Left ventricular hypertrophy (LVH): left axis deviation, tall R in V5-V6
• ST-T changes in LV strain
• Atrial fibrillation in older patients with longstanding HF

• "3 sign" on PA view: upper part = dilated left subclavian artery (or aorta above), middle = indentation of coarctation, lower = post-stenotic dilation of descending aorta
• "Reverse 3 sign" (Sigma sign) on barium swallow
• Rib notching (classic): bilateral erosions of the inferior margins of the 3rd-8th ribs due to dilated intercostal arteries (collaterals); seen after 5 years of age
• Normal or slightly enlarged cardiac silhouette
• Normal pulmonary vascularity (no L→R shunt at this level)
• Dilated ascending aorta (if bicuspid AV)

• Parasternal/suprasternal views: visualize aortic arch and coarctation
• Doppler: high velocity flow at coarctation site; gradient estimation
• Diastolic "runoff" pattern on descending aortic Doppler (low-resistance pattern distally = diagnostic)
• LV hypertrophy, function
• Associated bicuspid AV assessment
• Doppler gradient: mean >20 mmHg at rest, >40 mmHg exercise = significant

• Precise anatomical delineation of coarctation location, length, degree
• Collateral vessel quantification
• Aortic arch anatomy
• LV mass and function
• Preferred pre- and post-operative assessment

• Detailed anatomy
• Useful when MRI not available

• Definitive pressure measurement across coarctation
• Performed at time of balloon angioplasty/stenting

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Differential Diagnosis

• Takayasu arteritis (acquired aortic narrowing - different age, ESR elevated, constitutional symptoms)
• Aortic arch hypoplasia
• Midaortic syndrome (rare)
• Essential hypertension (no pulse discrepancy)

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Treatment

• Angiography confirms anatomy → balloon dilation ± stent placement
• Stenting preferred over plain angioplasty in adults (less recoarctation)
• Covered stents for calcified or complex lesions
• Can be performed for native coarctation or recoarctation

• Resection with end-to-end anastomosis: most common procedure in infants/children
• Patch aortoplasty: with synthetic patch (risk of aneurysm at repair site)
• Subclavian flap repair: uses left subclavian artery as flap; may compromise left arm blood flow
• Bypass graft (tube graft): for long-segment coarctation, calcified lesions, or complex anatomy
• Operative mortality: <1% in elective cases without associated defects

• Peak-to-peak systolic gradient across coarctation ≥20 mmHg (invasive measurement)
• Upper extremity hypertension + evidence of collateral circulation (even with smaller gradient)
• Symptomatic coarctation at any age

• Antihypertensive therapy (beta-blockers preferred): important before and after repair
• Post-repair hypertension common (remodeling takes years)
• ACE inhibitors/ARBs for LV dysfunction

• Systemic hypertension → LVH, HF
• Premature CAD
• Aortic dissection/aneurysm (especially at coarctation site)
• Berry aneurysm of the circle of Willis (3-5% of patients) → subarachnoid hemorrhage
• Infective endarteritis
• Stroke

• Recoarctation (10-20% after surgery/angioplasty)
• Aortic aneurysm at repair site
• Persistent hypertension (~50% remain hypertensive post-repair if repaired >25 years)
• Paraplegia (rare - aortic cross-clamp during surgery)

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QUESTION 51: TETRALOGY OF FALLOT

Anomalies Characterizing the Defect (The 4 Components)

1. Right ventricular outflow tract obstruction (RVOTO): infundibular (subpulmonic muscular obstruction - most common), valvular pulmonary stenosis (fused leaflets), annular hypoplasia, supravalvular, or combination; severity determines degree of cyanosis
2. Large, unrestrictive, misaligned VSD: non-restrictive perimembranous VSD - equalization of ventricular pressures
3. Overriding aorta: aortic root positioned above the VSD, receiving blood from both RV and LV (degree of override varies 30-95%)
4. RV hypertrophy: secondary to RVOTO and high RV pressure; RV wall thickness equals LV

• Right-sided aortic arch: 25% (arch goes over right bronchus)
• ASD/PFO: "pentalogy of Fallot"
• Anomalous left anterior descending coronary artery from right coronary artery (important pre-surgical finding - crosses RVOT)
• Absence of pulmonary valve (tetralogy with absent pulmonary valve)
• Muscular or additional VSDs

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Basic Hemodynamic Changes

• RVOTO creates high RV pressure equal to LV pressure (non-restrictive VSD)
• RV systolic pressure ≈ LV systolic pressure ≈ systemic pressure
• Degree of R→L shunting depends on: (1) severity of RVOTO, (2) systemic vascular resistance (SVR)
• When SVR falls (exercise, vasodilation): more deoxygenated blood shunts R→L across VSD → "tet spell" (hypoxic episode)
• When SVR rises (squatting, leg crossing): increases SVR → reduces R→L shunt → improves oxygenation (explains "squatting" behavior in children)
• Decreased pulmonary blood flow → chronic systemic hypoxemia → polycythemia, clubbing, cyanosis

• Sudden worsening cyanosis, hyperpnea, agitation, followed by syncope or death
• Triggered by: crying, feeding, exercise, fever, morning waking (↓ SVR)
• Mechanism: RVOTO ± ↓ SVR → ↑ R→L shunting → severe hypoxemia → hyperventilation → ↑ CO2 removal → paradoxically worsens by ↓ PCO2 (stimulates hyperpnea, which ↓ venous return)
• Management: knee-chest (squatting) position, O2, morphine (reduces hyperpnea), IV propranolol (↓ RVOT spasm), phenylephrine (↑ SVR), IV fluids, sodium bicarbonate

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Clinical Picture

1. Classical cyanotic TOF: moderate-severe RVOTO; R→L shunting predominates; cyanosis from birth
2. "Pink" (acyanotic) TOF: mild RVOTO; minimal R→L shunting; may be initially acyanotic; gradually develops cyanosis by age 1-3 years as infundibulum hypertrophies
3. TOF with pulmonary atresia (most severe): no forward flow through RVOT; dependent on collaterals (MAPCAs = major aortopulmonary collateral arteries) or PDA for pulmonary blood flow
4. Repaired TOF adults: surgically corrected; long-term complications predominate

• Neonates/infants: cyanosis (worse with crying/feeding), tet spells
• Older children: exercise intolerance, cyanotic spells, squatting behavior
• Adolescents/adults (repaired): well-tolerated initially; then pulmonary regurgitation (from repair), RV dilation, RV failure, arrhythmias (VT, AF)

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Physical Examination

Inspection

• Central cyanosis (lips, tongue, mucous membranes): depends on RVOTO severity
• Clubbing (digital) of fingers and toes: chronic hypoxemia
• Polycythemia signs: plethora, ruddy complexion
• Hypercyanotic spells (in infants): acute worsening cyanosis, hyperpnea
• Growth retardation
• Normal or mildly small body habitus

Palpation

• RV heave (hypertrophied RV) at left sternal border
• Systolic thrill at left sternal border (RVOT turbulence)
• Peripheral pulses: normal character (no bounding pulse - no L→R shunt)
• No LV heave (blood preferentially exits aorta from both ventricles)

Percussion

• Normal cardiac dullness (heart size is normal in TOF - RV hypertrophy with concentric enlargement)
• Hepatomegaly only in right HF (late)

Auscultation

• Systolic ejection murmur (SEM) at left sternal border: due to RVOTO (pulmonary stenosis)
• No separate VSD murmur (non-restrictive VSD with equalized pressures = no gradient = no murmur across VSD)
• Soft P2 or absent P2 (reduced pulmonary flow)
• Single S2 (pulmonary component inaudible or absent)
• No VSD murmur (paradox: the larger the VSD, the smaller/absent the murmur because pressure equalization)
• Adults post-repair: early diastolic murmur of pulmonary regurgitation (from patch repair or valvotomy), RV S3 if RV failure

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Laboratory

• CBC: polycythemia (elevated Hgb, Hct, RBC count); elevated WBC if concurrent infection
• Iron studies: iron deficiency anemia can mask polycythemia but worsen symptoms (microcytic RBCs increase blood viscosity disproportionately)
• Coagulation: thrombocytopenia and coagulopathy with severe polycythemia (platelet consumption, shortened platelet survival)
• ABG: hypoxemia (PaO2 reduced), compensatory metabolic alkalosis
• Uric acid: elevated (increased cell turnover from polycythemia)
• Creatinine: may be elevated from chronic hypoxemia/polycythemia and renal hypoperfusion
• BNP: elevated if RV dysfunction (post-repair adults)

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Instrumental Diagnostics

• Right axis deviation (RAD)
• RV hypertrophy: tall R in V1, deep S in V5-6 (R > S in V1)
• Right bundle branch block (RBBB) pattern - especially post-repair (right ventriculotomy)
• P pulmonale (RA enlargement)
• Post-repair: prolonged QRS duration (>180 ms) = marker of sudden death risk

• Normal cardiac size (RV hypertrophy is concentric, not dilating)
• "Boot-shaped" cardiac silhouette: concave main pulmonary artery segment (hypoplastic PA) creates distinctive left heart border; elevated apex (RV pushes LV upward)
• Decreased pulmonary vascular markings (oligemia - reduced pulmonary blood flow)
• Right-sided aortic arch in 25% (rightward deviation of trachea)
• Absence of MPA segment on left heart border

• Confirms 4 components: RVOTO, VSD, overriding aorta, RVH
• Doppler: RVOT gradient, pulmonary valve morphology
• Evaluate for associated anomalies
• Coronary artery anatomy (important for surgery)
• In repaired adults: RV size/function, degree of pulmonary regurgitation (PR), residual RVOTO, residual VSD

• Most important tool for adult TOF management
• RV volumes (RVEDV >160 mL/m² = indication for pulmonary valve replacement)
• Quantify pulmonary regurgitation fraction (>25% is significant)
• RV systolic function (RVEF <45% = indication for PVR)
• LV function assessment

• Pre-surgical hemodynamic assessment
• Coronary angiography (anomalous LAD from RCA crosses RVOT - must know before surgery)
• Measurement of RVOT/PA gradient
• Branch PA pressures (stenosis assessment)

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Treatment

• Blalock-Taussig (BT) shunt: subclavian artery → pulmonary artery anastomosis; increases pulmonary blood flow; now usually modified BT shunt (Gore-Tex tube graft)
• Potts shunt (aorta to left PA), Waterston shunt (ascending aorta to right PA): historical; rarely used now
• Indication: severe cyanosis in small infant not suitable for immediate complete repair; profound polycythemia
• PGE1 (prostaglandin E1): IV infusion in neonates with severe cyanosis to maintain ductal patency

• Optimal age: 3-6 months for most centers (or earlier if severe cyanosis)
• Technique:
  • Close VSD with synthetic patch (route through right atrium or right ventricle)
  • Relieve RVOTO: resect infundibular muscle, pulmonary valvotomy/valvectomy, patch enlargement of RVOT/pulmonary annulus (transannular patch)
  • Pericardial or synthetic patch for RVOT reconstruction
• Transannular patch (for small annulus): relieves obstruction but creates pulmonary regurgitation - the major long-term complication
• 30-year survival post-repair: >90%

1. Knee-chest position (squatting equivalent - ↑ SVR, ↓ R→L shunting)
2. High-flow O2
3. IV morphine sulfate (0.1 mg/kg) - reduces hyperpnea and agitation
4. IV phenylephrine (0.02 mg/kg) - ↑ SVR
5. IV propranolol (0.01-0.02 mg/kg) - reduces RVOT spasm (dynamic obstruction)
6. IV sodium bicarbonate (1 mEq/kg) - correct metabolic acidosis
7. If no response: ketamine IV (↑ SVR, good analgesia for infants), consider urgent surgery

• Pulmonary valve replacement (PVR): indicated for severe PR with:
  • RVEDV >160 mL/m² on MRI
  • RVEF <45%
  • Sustained VT
  • Progressive exercise intolerance
  • Options: surgical bioprosthesis or percutaneous pulmonary valve implantation (Melody/SAPIEN valve via catheter)
• ICD implantation: for sustained VT or VF; risk factors: QRS duration >180 ms, LV dysfunction, severe PR, inducible VT on EPS
• Antiarrhythmic therapy: beta-blockers, amiodarone
• Catheter ablation: for atrial arrhythmias (AFL, AF) - very common in repaired TOF adults due to right atrial scarring
• Regular follow-up (every 1-2 years at ACHD center): ECG, echocardiography, exercise testing, cardiac MRI every 3-5 years

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Summary of All 11 Questions Answered

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Q41 - Pericarditis

• Etiology: viral/idiopathic (85%), TB, bacterial, SLE, RA, uremia, neoplastic, drug-induced, post-MI (Dressler), radiation
• Physical exam: Ewart's sign, pericardial friction rub (3 components at LLSB), pericardial knock in constrictive
• ECG: 4 stages - diffuse concave ST elevation + PR depression → T inversion → normalization; differs from STEMI (diffuse, no reciprocal changes)
• Treatment: Aspirin 650 mg q6h + Colchicine 0.5-1.2 mg/day x 3 months; etiology-specific (anti-TB, dialysis for uremia, corticosteroids only if NSAIDs fail); pericardiectomy for constrictive disease and refractory recurrences

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Q42 - Cardiac Tamponade

• Beck's triad: Hypotension + elevated JVP + muffled heart sounds
• Hemodynamics: Equalization of diastolic pressures; pulsus paradoxus; electrical alternans on ECG
• Echo gold standard: RV diastolic collapse, plethoric IVC, respiratory variation in mitral inflow
• Treatment: Echo-guided pericardiocentesis; surgical drainage for organized/multiloculated effusions, purulent pericarditis, trauma

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Q43/Q44 - Myocarditis

• Etiology: Coxsackievirus B (West), Chagas (worldwide); toxic (checkpoint inhibitors increasingly important)
• Pathogenesis: 3 phases - direct viral injury → immune-mediated injury (molecular mimicry) → chronic autoimmune cardiomyopathy
• Clinical variants: Fulminant (acute, best prognosis), Acute non-fulminant, Chronic active, Chronic persistent
• Mayo Clinic classification: Lymphocytic, Eosinophilic, Giant cell (most aggressive), Granulomatous, Chagas
• Gold standard diagnosis: CMR (Lake Louise criteria) + Endomyocardial biopsy (Dallas criteria + immunohistochemistry + PCR)
• Treatment: Activity restriction 6 months + GDMT (ACE-I, BB, diuretics, SGLT2i) + Mechanical circulatory support for fulminant; immunosuppression for giant cell/autoimmune; no immunosuppression for viral

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Q45 - Congenital Heart Disease (General)

• Etiology: Down syndrome (AV canal), Turner (coarctation), 22q11 (TOF), rubella (PDA, PS, ASD), maternal diabetes (TGA)
• Classification: Simple / Moderate / Complex; by hemodynamic type: L→R shunts, obstructive, R→L (cyanotic)
• Prevalence in adults: ASD (30-40%), VSD (15-20%), PDA (5-10%), Bicuspid AV (2% of population)

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Q46 - PDA

• Classic murmur: "Machinery" (Gibson) - continuous crescendo-decrescendo at 1st-2nd left ICS
• Differential cyanosis: toes cyanotic, fingers normal (Eisenmenger PDA)
• Treatment: Ibuprofen/indomethacin (premature infants only); device closure (coil/Amplatzer) in adults; surgical ligation; contraindicated in Eisenmenger

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Q47 - ASD

• Hallmark auscultation: Wide FIXED splitting of S2 + soft pulmonary ejection murmur
• ECG hallmark: Incomplete RBBB (rSR' in V1)
• Types: Secundum (70%, device closure), Primum (surgery needed - cleft MV), Sinus venosus (surgery needed - anomalous pulmonary veins)
• Treatment: Device closure (Amplatzer) for secundum ASD <3.5 cm; surgery for all others

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Q48 - VSD

• Paradox: Louder murmur = smaller, more restrictive VSD (Roger's disease)
• Murmur: Holosystolic at lower left sternal border (4th ICS) ± thrill
• Classification: Perimembranous (70-80%), Muscular (15-20%), Outlet/supracristal (5-7%, Asian population, AR risk), Inlet (AV canal type)
• Treatment: Spontaneous closure common in small defects; device or surgical patch closure when Qp:Qs ≥2:1 or LV dilation

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Q49 - Congenital Aortic Valve Stenosis

• Bicuspid AV: Most common adult CHD; accounts for 50% of surgical AS
• Classic triad: Angina (5-yr survival) → Syncope (3-yr) → Heart failure (2-yr) without AVR
• Parvus et tardus pulse + late-peaking ejection systolic murmur + absent A2 + S4
• Treatment: TAVR (preferred in intermediate/high surgical risk); SAVR (preferred <65 years); balloon valvuloplasty as bridge only

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Q50 - Coarctation of the Aorta

• Classic signs: "3 sign" on CXR + rib notching (3rd-8th ribs) + brachial-femoral pulse delay
• Associations: Turner syndrome (35%), bicuspid AV (50% of coarctation patients), berry aneurysms (3-5%)
• Treatment: Balloon angioplasty + stent in adults; surgical resection/end-to-end anastomosis in infants; treat persistent hypertension with beta-blockers post-repair

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Q51 - Tetralogy of Fallot

• 4 components: RVOTO + large non-restrictive VSD + overriding aorta + RVH (all from single embryologic defect - infundibular septum deviation)
• "Boot-shaped heart" on CXR + decreased pulmonary markings + right aortic arch (25%)
• No VSD murmur (non-restrictive VSD - no gradient); ejection murmur from RVOTO
• Tet spell management: Knee-chest position + O2 + morphine + phenylephrine + propranolol
• Long-term (repaired adults): Pulmonary regurgitation → RV dilation → indication for PVR (RVEDV >160 mL/m² on MRI); ICD for QRS >180 ms/VT risk