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QUESTION 31 & 32: Cardiomyopathy - Etiology, Pathogenesis, Classification, Clinical Manifestations, Diagnostics, Differential Diagnosis, Treatment, Surgical Treatment, Prevention; Primary vs Secondary Cardiomyopathy

Definition

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Classification (Traditional Morphologic)

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Primary vs Secondary Cardiomyopathy

• Primary (idiopathic): Disease intrinsic to the myocardium without identifiable systemic cause. Can be genetic (sarcomere mutations), inflammatory (myocarditis), or idiopathic.
• Secondary: Myocardial involvement as part of a systemic/generalized disease process.

• Infiltrative: Amyloidosis, sarcoidosis, Gaucher's disease, Hurler's disease
• Storage diseases: Hemochromatosis, Fabry disease, glycogen storage diseases
• Endomyocardial: Endomyocardial fibrosis, hypereosinophilic syndrome
• Inflammatory (granulomatous): Sarcoidosis
• Endocrine: Diabetes mellitus, hyperthyroidism, hypothyroidism, Cushing's disease, acromegaly
• Cardiofacial syndromes: Noonan syndrome, LEOPARD syndrome
• Neuromuscular disorders: Duchenne-Becker muscular dystrophy, Emery-Dreifuss dystrophy, myotonic dystrophy
• Nutritional deficiencies: Beriberi (thiamine), selenium deficiency
• Autoimmune/collagen vascular: SLE, rheumatoid arthritis, scleroderma, dermatomyositis
• Toxins: Alcohol, cocaine, doxorubicin, radiation
• Peripartum: Peripartum cardiomyopathy

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Pathogenesis Overview

• Sarcomere mutations: Most common cause of HCM (beta-myosin heavy chain, myosin-binding protein C)
• Cytoskeletal mutations: Lead to DCM (dystrophin, titin, lamin A/C, desmin)
• Calcium handling abnormalities: Central in HCM and some arrhythmic phenotypes
• Immune/inflammatory pathways: Myocarditis evolving to cardiomyopathy; nearly 1 in 5 inflammatory myocarditis patients harbor pathogenic cardiomyopathy variants

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Diagnostic Evaluation (General for All Cardiomyopathies)

• ECG
• Chest radiograph
• 2D and Doppler echocardiography
• Cardiac MRI (evidence of myocardial inflammation and fibrosis)

• Serum electrolytes (Na, K, Ca, Mg)
• Fasting glucose / HbA1c
• Creatinine, BUN, LFTs
• Lipid profile
• TSH (thyroid function)
• Serum iron, transferrin saturation
• Urinalysis
• Creatine kinase isoforms, cardiac troponin
• CBC with differential

• Respiratory pathogen panel
• HIV, Chagas' disease (T. cruzi), Lyme disease, toxoplasmosis, trichinosis serology
• Genetic counseling and multigene cardiomyopathy panel
• Rheumatologic serologies
• Endomyocardial biopsy (with electron microscopy for storage diseases)
• Coronary angiography (if ischemia suspected)

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QUESTION 33: Hypertrophic Cardiomyopathy (HCM)

Definition & Epidemiology

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Genetics & Pathogenesis

• Autosomal dominant inheritance in the majority
• Most commonly caused by mutations in beta-myosin heavy chain (MYH7) and myosin-binding protein C (MYBPC3) - both sarcomere proteins
• Results in asymmetric septal hypertrophy with dynamic left ventricular outflow tract (LVOT) obstruction in ~70% of patients
• Abnormal myocyte arrangement (disarray), interstitial fibrosis
• Impaired diastolic relaxation due to stiff, hypertrophied myocardium

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Classification

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Hemodynamic Disorders

• Dynamic LVOT obstruction caused by systolic anterior motion (SAM) of the mitral valve
• Mitral regurgitation (eccentric) commonly associated
• Diastolic dysfunction (impaired relaxation, elevated filling pressures)
• Abnormal response to exercise: BP may fail to rise or fall (poor prognostic sign)

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Clinical Manifestations

• Exertional dyspnea (most common - due to diastolic dysfunction + obstruction)
• Chest pain (angina - from ischemia due to microvascular disease + increased demand)
• Palpitations
• Syncope or presyncope (especially exertional - from LVOT obstruction or arrhythmia)
• Sudden cardiac death - often the first presentation in young athletes

• Harsh systolic ejection murmur at LLSB - increases with Valsalva (decreased preload), decreases with squatting
• Bifid carotid pulse (pulsus bisferiens)
• Sustained LV apical impulse
• S4 gallop (from vigorous atrial contraction against stiff LV)
• Paradoxical splitting of S2 (with severe obstruction)

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Diagnostics

• LV hypertrophy pattern
• Deep Q waves in inferolateral leads (not due to infarction)
• ST/T wave changes
• Preexcitation (WPW) in some

• Asymmetric septal hypertrophy (ASH)
• SAM (systolic anterior motion of mitral valve)
• LVOT gradient measurement
• Diastolic dysfunction grading

• Precise wall thickness measurement
• Late gadolinium enhancement (LGE) indicates fibrosis - prognostic marker
• Identifies apical aneurysms

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Differential Diagnosis

• Hypertensive heart disease (LVH from HTN)
• Aortic stenosis (fixed obstruction)
• Athlete's heart (physiologic hypertrophy - ≤12 mm, no symptoms, normal Doppler)
• Fabry disease (x-linked lysosomal storage - pseudohypertrophy)
• LEOPARD/Noonan syndrome (syndromic HCM in children)
• Amyloidosis (infiltrative - "sparkling" echo, restrictive pattern)

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Complications

• Sudden cardiac death (ventricular tachyarrhythmias)
• Atrial fibrillation + stroke (15-25% lifetime risk)
• Progressive heart failure (HCM-rEF in ~5%)
• Infective endocarditis (uncommon)

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Treatment

1. Beta-blockers (first-line for obstructive symptoms) - slow heart rate, enhance diastolic filling, decrease contractility
2. Verapamil (L-type calcium channel blocker) - alternative/additive to beta-blockers
3. Disopyramide - added for persistent exertional dyspnea; potent negative inotrope
4. Mavacamten (FDA-approved cardiac myosin inhibitor) - shown high efficacy for symptomatic obstructive HCM, including patients with persistent symptoms despite beta-blocker; also aficamten (under investigation)
5. Diuretics - for fluid retention and venous congestion (with or without obstruction)

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Surgical Treatment - Indications

1. Surgical myectomy (Morrow procedure) - gold standard
   • Excises septal myocardium involved in dynamic obstruction
   • Extremely low perioperative mortality at experienced centers
   • Excellent long-term survival, free from recurrent obstruction
   • Mitral valve repair usually unnecessary (MR resolves with myectomy)
   • Most common complication: complete heart block requiring permanent pacing
2. Alcohol septal ablation (Percutaneous)
   • Requires suitable coronary anatomy
   • Controlled infarction of proximal septum
   • Similar gradient reduction to myectomy
   • Reserved for patients who wish to avoid surgery or have significant comorbidities
   • Most common complication: complete heart block

• Indicated for patients with ≥1 major risk factor for sudden death
• Major risk factors include: young age, nonsustained VT, failure of BP to rise with exercise, recent syncope (within 6 months), ventricular wall thickness >3 cm

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Prevention

• Genetic testing and family screening
• Restriction from competitive sports (historically; recent evidence suggests shared decision-making about exercise)
• ICD for high-risk patients
• Anticoagulation for AF

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QUESTION 34: Dilated Cardiomyopathy (DCM)

Definition

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Etiology & Classification

• Mutations in genes for structural proteins: titin (TTN - most common), lamin A/C (LMNA), dystrophin, desmin (DES)
• Autosomal dominant, recessive, X-linked, and mitochondrial patterns
• Lamin A/C and SCN5A mutations particularly associated with conduction system disease and ventricular arrhythmias

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Clinical Manifestations

• Progressive exertional dyspnea, orthopnea, PND
• Fatigue and exercise intolerance (reduced cardiac output)
• Peripheral edema, ascites (right heart failure)
• Palpitations (atrial and ventricular arrhythmias)
• Embolic events (LV thrombus/AF)

• Cardiomegaly (displaced, diffuse apex beat)
• S3 gallop (volume overload, dilated LV)
• Functional mitral regurgitation murmur (dilated annulus)
• Elevated JVP, peripheral edema, hepatomegaly (right heart involvement)
• Pulsus alternans (severe LV dysfunction)

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Diagnostics

• ECG: LBBB pattern, LVH, atrial fibrillation, nonspecific ST-T changes, Q waves
• Echo: Dilated LV, global hypokinesia, LVEF ≤40%, functional MR, LV thrombus
• BNP/NT-proBNP: Elevated, correlates with severity
• Cardiac MRI: Intramural or subepicardial LGE pattern (vs. subendocardial in ischemic disease)
• Coronary angiography: To exclude ischemic cardiomyopathy
• Genetic testing: Multigene cardiomyopathy panel
• Endomyocardial biopsy: For suspected specific diagnoses (giant cell myocarditis, sarcoidosis, hemochromatosis, eosinophilic myocarditis)

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Differential Diagnosis

• Ischemic cardiomyopathy (subendocardial LGE on MRI, CAD on angiography)
• Alcoholic cardiomyopathy (history + abstinence may lead to recovery)
• Hypertensive heart disease
• Valvular heart disease (aortic/mitral)
• Tachycardia-induced cardiomyopathy (rate control reverses LV dysfunction)
• Giant cell myocarditis (acute, rapidly progressive, biopsy-proven)

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Treatment

1. ACE inhibitors / ARBs (or sacubitril/valsartan - ARNI) - reduce mortality/morbidity
2. Beta-blockers (carvedilol, metoprolol succinate, bisoprolol) - reduce mortality
3. Mineralocorticoid receptor antagonists (spironolactone, eplerenone) - reduce mortality
4. SGLT2 inhibitors (dapagliflozin, empagliflozin) - reduce HF hospitalizations and mortality
5. Diuretics (loop diuretics) - symptom relief
6. Hydralazine + nitrate - if ACE-I/ARB intolerant (especially in Black patients)
7. Ivabradine - if HR remains elevated on max beta-blocker
8. Digoxin - for rate control in AF; modest symptomatic benefit

• ICD: LVEF ≤35% + NYHA II-III + optimal medical therapy ≥3 months
• CRT (Cardiac Resynchronization Therapy): LVEF ≤35% + LBBB with QRS ≥150 ms + NYHA II-IV

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Surgical Indications

• Heart transplantation: End-stage DCM, LVEF ≤25%, refractory symptoms despite optimal medical and device therapy
• LVAD (Left Ventricular Assist Device): Bridge to transplant, destination therapy for ineligible transplant patients
• Mitral valve repair: Functional MR with severe symptoms
• Catheter ablation: For recurrent VT associated with cardiomyopathy scarring

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Prevention

• Genetic screening of first-degree relatives
• Alcohol abstinence (reversal possible with early abstinence)
• Cardioprotective protocols during chemotherapy (anthracyclines)
• Prophylactic beta-blockers before/during cardiotoxic therapy
• Treatment of underlying tachycardia (tachycardia-induced DCM is reversible)

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QUESTION 35: Restrictive Cardiomyopathy (RCM)

Definition

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Classification (Etiology)

• Endomyocardial fibrosis (tropical, most prevalent worldwide)
• Hypereosinophilic syndrome (Loeffler's endocarditis)
• Radiation-induced fibrosis

• Amyloidosis (transthyretin - ATTR and light chain - AL) - increasing emphasis in diagnosis
• Sarcoidosis

• Hemochromatosis
• Fabry disease
• Glycogen storage diseases

• Post-radiation
• Scleroderma

• Desmin (DES) mutations - combined cardiac and skeletal myopathy
• Sarcomere variants - overlap with HCM

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Hemodynamic Pattern

• "Square root" sign (dip-and-plateau) on RV pressure tracing
• Elevated and equalized diastolic filling pressures (RVEDP = LVEDP)
• Normal or near-normal systolic function (EF ≥50%)
• Reduced stroke volume and cardiac output
• Elevated BNP/NT-proBNP

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Clinical Manifestations

• Exertional dyspnea (predominant symptom)
• Exercise intolerance
• Right heart failure symptoms: edema, ascites, hepatomegaly, JVP elevation
• Kussmaul's sign (paradoxical rise in JVP with inspiration)
• Palpitations (AF common)
• Syncope (rare)

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Diagnostics

• Echocardiography: Normal or mildly reduced EF, biatrial enlargement, diastolic dysfunction grade III-IV, Doppler: restrictive filling pattern (E>>A, short deceleration time), myocardial granular "sparkling" in amyloidosis
• Cardiac MRI: Global subendocardial LGE in AL amyloidosis, patchy in sarcoidosis; diffuse RV/LV involvement
• ECG: Low voltage (especially in amyloidosis - classic "voltage-mass mismatch"), conduction defects, arrhythmias
• Biopsy: Endomyocardial biopsy; Congo red staining (amyloid - apple-green birefringence); rectal/abdominal fat aspirate for AL amyloidosis
• Nuclear imaging: Technetium pyrophosphate (Tc-PYP) scan for ATTR amyloidosis (high specificity)
• Serum/urine protein electrophoresis + free light chains: For AL amyloidosis
• Genetic testing: For hereditary ATTR, Fabry disease, desminopathy

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Differential Diagnosis

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Treatment

• ATTR amyloidosis: Tafamidis (FDA-approved stabilizer; reduces mortality and hospitalizations), patisiran/inotersen (RNA-targeted therapy for hereditary ATTR with polyneuropathy)
• AL amyloidosis: Chemotherapy (bortezomib-based regimens), autologous stem cell transplant
• Hemochromatosis: Phlebotomy, chelation therapy
• Fabry disease: Enzyme replacement therapy
• Sarcoidosis: Corticosteroids
• Eosinophilic myocarditis: Corticosteroids, excision of thrombus

• Diuretics (carefully - risk of hypotension)
• Rate control for AF; anticoagulation
• Pacemaker/ICD for conduction disease/arrhythmias (especially in sarcoidosis, amyloidosis)

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Surgical Indications

• Pericardiectomy: Not applicable (this is for constrictive pericarditis)
• Surgical excision: Endomyocardial fibrosis (resection of fibrotic endocardium)
• Heart transplantation: End-stage RCM in appropriate candidates (contraindicated in amyloidosis with systemic involvement)
• Valve surgery: As needed for severe valvular disease

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QUESTION 36 & 37: Infective Endocarditis

Definition

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Epidemiology

• Incidence: ~15 cases per 100,000 population per year in the United States
• In developed countries, 25-35% of native-valve IE (NVE) is health care-associated
• 16-30% of all cases involve prosthetic valves (PVE)
• S. aureus has become the most common causative organism in developed countries
• Recent acceleration in younger patients (aged 25-44) associated with opioid use disorder

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Etiology

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Pathological Anatomy

• High-velocity jets damage endothelium (e.g., mitral regurgitation jet)
• Sterile fibrin-platelet thrombus forms (non-bacterial thrombotic endocarditis)
• Bacteria adhere, proliferate within the vegetation
• Vegetations grow by layered deposition; bacteria protected from antibiotics and phagocytes
• Pathological consequences: valve destruction, perivalvular extension (abscess), emboli

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Classification

• Acute IE: Hectically febrile, rapidly damages cardiac structures, seeds extracardiac sites; progresses to death within weeks if untreated (S. aureus)
• Subacute IE: Indolent course, gradual structural damage, rarely metastasizes; gradually progressive unless major embolic event (viridans strep)

• Native valve endocarditis (NVE)
• Prosthetic valve endocarditis (PVE) - early (<1 year): coag-negative staph; late (>1 year): similar to NVE
• CIED-IE (Cardiovascular Implantable Electronic Device endocarditis)

• Health care-associated
• Injection drug use (IDU) - right-sided (tricuspid) more common
• Community-acquired

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Primary vs Secondary Endocarditis

• Primary (NVE): Infection of a previously normal or minimally diseased valve
• Secondary: Infection superimposed on pre-existing valve disease (rheumatic disease, MVP, bicuspid aortic valve, prosthetic valve, congenital lesions)

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Clinical Manifestations

• Fever (most common - >90%)
• Chills, sweats, malaise, anorexia, weight loss
• Arthralgia, myalgia
• New regurgitant murmur (60-85%)

• Petechiae: Conjunctival, palatal, skin
• Splinter hemorrhages: Linear subungual hemorrhages (non-specific)
• Osler nodes: Painful, tender nodules on finger/toe pads (immune complex mediated)
• Janeway lesions: Non-tender erythematous macules on palms/soles (septic emboli)
• Roth spots: Oval retinal hemorrhages with pale centers
• Clubbing (subacute, long-standing)

• Stroke (cerebral emboli - most common serious complication)
• Pulmonary emboli (right-sided IE)
• Splenic infarct, renal infarct
• Mycotic aneurysms

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Diagnostics

• Three sets from different venipuncture sites, 30+ minutes apart
• If subacute IE suspected and patient is stable, cultures before antibiotics
• If acute IE or hemodynamically unstable: cultures immediately, start antibiotics

• TTE: Specifically confirms vegetations; inadequate in 20%; misses 20-35% vegetations
• TEE: Detects vegetations >90%; should be performed when TTE inconclusive, prosthetic valve, or complications suspected; sensitivity 90%+; false-negative 6-18%
• TEE indications: PVE, CIED-IE, suboptimal TTE, intracardiac complications suspected

• PCR/NAT: Identifies C. burnetii, Bartonella, T. whipplei from blood
• Indirect immunofluorescence: Bartonella IgG ≥1:800
• Next-generation metagenomic sequencing (investigational)
• 18F-FDG PET scan: Useful for PVE and CIED-IE

• Cardiac CT angiogram: Superior for pseudoaneurysm, abscess; can substitute pre-op cardiac catheterization
• Chest radiograph (pulmonary emboli in right-sided IE)
• Brain MRI (embolic strokes)

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Modified Duke Criteria (2015 / Duke-ISCVID Update)

Major Criteria:

• Typical microorganism from 2 separate cultures: viridans strep, S. bovis group, HACEK, S. aureus, community-acquired enterococci
• Persistently positive cultures (≥2 positive cultures ≥12 hours apart)
• Single positive culture for Coxiella burnetii (Q fever) or anti-phase 1 IgG ≥1:800
• Positive PCR/NAT from blood for C. burnetii, Bartonella, or T. whipplei
• Bartonella IgG ≥1:800

• Echocardiographic evidence: oscillating intracardiac mass, abscess/fistula, new partial dehiscence of prosthetic valve, new valvular regurgitation
• Positive 18F-FDG PET/CT (abnormal activity around prosthetic valve ≥3 months post-implant)
• Positive radiolabeled WBC SPECT/CT

Minor Criteria:

1. Predisposing heart condition or injection drug use
2. Fever ≥38°C
3. Vascular phenomena (major emboli, septic pulmonary emboli, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions)
4. Immunologic phenomena (glomerulonephritis, Osler nodes, Roth spots, rheumatoid factor)
5. Microbiological evidence: positive culture not meeting major criteria
6. Echocardiographic findings not meeting major criteria
7. New valvular regurgitation (not meeting major criteria)

Case Definitions:

• Definite IE: 2 major; or 1 major + 3 minor; or 5 minor criteria; or pathological diagnosis
• Possible IE: 1 major + 1 minor; or 3 minor criteria
• Rejected IE: Alternative diagnosis confirmed; or resolution of symptoms with ≤4 days antibiotics; or no pathologic evidence at surgery/autopsy after ≤4 days

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Complications

• Cardiac: Heart failure (most common cause of death), perivalvular abscess, fistula, complete heart block, prosthetic valve dehiscence
• Neurological: Embolic stroke (15-20%), brain abscess, meningitis, mycotic aneurysm, intracranial hemorrhage
• Septic emboli: Pulmonary (right-sided), splenic abscess, vertebral osteomyelitis
• Renal: Embolic infarcts, immune complex glomerulonephritis, drug nephrotoxicity
• Mycotic aneurysms: Intracranial, aortic, visceral

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Treatment

• Bactericidal antibiotics required (bacteriostasis insufficient)
• Prolonged duration necessary (4-6 weeks) to sterilize avascular vegetation
• Pending culture results: stable subacute IE patients may have antibiotics withheld to allow collection of additional blood cultures

1. Heart failure not responsive to medical therapy (most common indication)
2. Uncontrolled infection (persistent bacteremia >7 days despite appropriate antibiotics, fungi, highly resistant organisms)
3. Perivalvular extension: Abscess, fistula, destructive penetrating lesions
4. Embolic prevention: Large mobile vegetations (>10-15 mm) especially with recent embolism
5. Prosthetic valve IE with dehiscence, obstruction, or persisting infection
6. Recurrent emboli despite appropriate antibiotic therapy

• Emergency (within hours): Acute severe aortic regurgitation or MR with pulmonary edema, cardiac tamponade
• Urgent (within days): Uncontrolled infection, progressive paravalvular extension
• Elective (within weeks): Controlled infection with prosthetic valve or relative indications

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Prevention of Exacerbations (Antibiotic Prophylaxis)

1. Prosthetic cardiac valves or prosthetic material used for repair
2. Previous history of IE
3. Congenital heart disease (CHD):
   • Unrepaired cyanotic CHD (including palliative shunts/conduits)
   • Repaired CHD with residual defects at or adjacent to prosthetic patch/device
   • Completely repaired CHD within 6 months
4. Cardiac transplant recipients with valvulopathy

• All dental procedures involving gingival manipulation or oral mucosa perforation
• Respiratory tract procedures in high-risk patients
• NOT routine GI/GU procedures (per current guidelines)

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QUESTION 38: Heart Failure - Etiology, Pathogenesis, Classification

Definition

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Etiological Factors

• Most common cause in developed countries (~60-70% of HF)
• Acute MI, chronic ischemic cardiomyopathy

• Hypertension (HTN) - pressure overload leading to LVH then failure
• Dilated cardiomyopathy (idiopathic, familial, toxic, inflammatory)
• Valvular heart disease: Aortic stenosis/regurgitation, mitral regurgitation/stenosis
• Arrhythmias: Tachycardia-induced (AF, incessant SVT, VT)
• Metabolic: Diabetes, thyroid disease, hemochromatosis
• Toxic: Alcohol, anthracyclines, trastuzumab, cocaine
• Genetic cardiomyopathies
• Infectious: Viral myocarditis, Chagas, HIV
• Infiltrative: Amyloidosis, sarcoidosis
• Peripartum cardiomyopathy
• High-output HF: Severe anemia, AV fistula, Paget's disease, beriberi, hyperthyroidism

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Modern Pathogenesis

• Reduced renal perfusion activates renin release
• Angiotensin II: vasoconstriction, aldosterone release, sympathetic activation
• Aldosterone: Na/water retention, potassium wasting, myocardial fibrosis
• Beneficial short-term (maintains perfusion); harmful long-term (remodeling)

• Increased heart rate, contractility (short-term compensation)
• Chronic: beta-receptor downregulation, catecholamine cardiotoxicity, arrhythmias, apoptosis

• Released by stressed myocardium
• Counterregulatory: promote natriuresis, vasodilation, anti-fibrotic
• Overwhelmed in advanced HF

• Progressive LV dilation and shape change (spherical remodeling)
• Myocyte hypertrophy, apoptosis, and loss
• Interstitial fibrosis
• Functional mitral regurgitation (annular dilation)
• Perpetuates a vicious cycle of increasing wall stress and further dysfunction

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Classification

By LVEF (Hemodynamic Variants):

By Stages (ACC/AHA):

• Stage A: At risk for HF; no structural disease (HTN, DM, family history)
• Stage B: Structural disease; no symptoms
• Stage C: Structural disease + current or prior HF symptoms
• Stage D: Refractory, advanced HF requiring special interventions

By Functional Class (NYHA):

• Class I: No limitation of ordinary physical activity
• Class II: Slight limitation; symptoms with moderate exertion
• Class III: Marked limitation; symptoms with minimal exertion
• Class IV: Symptoms at rest; unable to carry any activity without discomfort

By Clinical Presentation:

• Acute decompensated HF (ADHF)
• Chronic HF (stable, compensated)
• High-output HF
• Right vs Left HF (or biventricular)

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QUESTION 39: Chronic Heart Failure - Clinical Picture, Physical Examination, Diagnostic Methods, Treatment

Clinical Picture of CHF

• Dyspnea on exertion (earliest and most common symptom)
• Orthopnea (dyspnea when lying flat; 2-3 pillow orthopnea)
• Paroxysmal nocturnal dyspnea (PND) - sudden awakening with breathlessness, relieved by sitting up
• Cough (especially nocturnal; frothy white/pink-tinged sputum in severe cases)
• Cardiac asthma (wheeze from airway edema - mimics bronchial asthma)
• Cheyne-Stokes respirations (central apnea alternating with hyperpnea; advanced HF)
• Fatigue, weakness, exercise intolerance (reduced cardiac output)
• Nocturia (redistribution of edema fluid when supine at night)
• Mental status changes (elderly patients)

• Peripheral edema (bilateral, pitting, dependent - ankles when ambulatory, sacrum when supine)
• Abdominal bloating, ascites
• Right upper quadrant discomfort (hepatic congestion)
• Anorexia, nausea (gut edema)
• Weight gain (fluid retention)

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Physical Examination

• Tachycardia (compensatory)
• Low blood pressure (severe dysfunction) or elevated BP (HTN-driven HF)
• Pulsus alternans (alternating strong/weak pulse - severe systolic dysfunction)
• Reduced pulse pressure (low output)
• Tachypnea, low SpO2

• Elevated JVP (most reliable sign of elevated right heart pressures)
• Hepatojugular reflux (abdominojugular test) - positive in right HF
• Kussmaul's sign: JVP rises with inspiration (restrictive physiology, severe RV failure)

• Bibasal crepitations/crackles (pulmonary edema)
• Pleural effusion (dullness to percussion, absent breath sounds at bases)
• Wheeze ("cardiac asthma")

• Cardiomegaly (laterally displaced, diffuse apical impulse)
• S3 gallop (pathognomonic in adults; volume overload, rapid ventricular filling - "Ken-tuc-ky")
• S4 gallop (LV hypertrophy, stiff ventricle - "Ten-nes-see")
• Murmurs of underlying valvular disease or functional MR/TR
• Paradoxical S2 splitting (LBBB or aortic stenosis)

• Hepatomegaly (tender, pulsatile in TR)
• Ascites (advanced, chronic right HF)
• Splenomegaly (rare)

• Bilateral pitting peripheral edema (ankles, legs, thighs, scrotum)
• Cyanosis (peripheral - reduced perfusion; central - severe pulmonary disease)
• Cool extremities (low output state)

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Laboratory Diagnostic Tests

• BNP (B-type natriuretic peptide) and NT-proBNP: Elevated; directly proportional to HF severity; used for diagnosis, risk stratification, and monitoring therapy
  • BNP >100 pg/mL (or NT-proBNP >300 pg/mL): HF likely
  • BNP <35 pg/mL (NT-proBNP <125 pg/mL): HF unlikely
• Troponin I/T: Elevated in myocyte injury, acute decompensation, poor prognosis
• Serum electrolytes: Hyponatremia (poor prognosis), hypokalemia (diuretics)
• Renal function: Creatinine, BUN (elevated - "cardiorenal syndrome" or diuretic effect)
• Liver function tests: Elevated AST, ALT, bilirubin (hepatic congestion)
• CBC: Anemia (comorbidity, worsens HF); leukocytosis (infection/inflammation)
• Fasting glucose / HbA1c: Diabetes as cause or comorbidity
• Thyroid function (TSH): Hypo/hyperthyroidism as cause
• Iron studies: Serum ferritin, transferrin saturation (iron deficiency is treatable comorbidity in HF)
• Lipid profile: Cardiovascular risk assessment
• Serum albumin: Nutritional status, edema formation

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Instrumental Diagnostic Studies

• LV hypertrophy (voltage criteria), LBBB (indicates dyssynchrony, CRT candidate)
• Q waves (ischemic etiology)
• Atrial fibrillation (common comorbidity and cause)
• Prolonged PR interval, bundle branch blocks

• Cardiomegaly (cardiothoracic ratio >0.5)
• Pulmonary venous congestion (upper lobe diversion)
• Interstitial edema: Kerley B lines (horizontal lines at lung bases)
• Alveolar edema ("bat wing" or "butterfly" pattern)
• Pleural effusions (blunting of costophrenic angles)

• LV and RV dimensions, wall thickness, wall motion abnormalities
• LVEF measurement (Simpson's biplane method)
• Diastolic function grading (E/A ratio, e' velocity, E/e' ratio)
• Valvular disease severity
• Estimation of filling pressures (E/e' >15 = elevated LV filling pressure)
• Pulmonary artery pressure estimation (TR jet velocity)
• RV size and function (TAPSE, FAC)
• Pericardial effusion

• Gold standard for LV/RV volumes and EF
• LGE for myocardial fibrosis/scar (ischemic vs non-ischemic pattern)
• Myocardial inflammation (T1, T2 mapping)
• Infiltrative disease (amyloid, hemochromatosis, sarcoidosis)
• Viability assessment

• To exclude ischemic etiology (required in most new HFrEF patients)

• Objective functional capacity (6-minute walk test, cardiopulmonary exercise testing)
• VO2 max: <14 mL/kg/min indicates need for advanced therapy

• Gold standard for hemodynamic assessment
• Measures CO, CI, PCWP, PAP, SVR, PVR
• Required before heart transplantation evaluation
• Guides therapy in refractory/advanced HF

• Accurate LVEF when echo technically difficult
• Myocardial perfusion imaging (ischemia evaluation)

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Treatment of CHF

HFrEF (EF <40%) - Guideline-Directed Medical Therapy (GDMT):

1. ARNI (Sacubitril/Valsartan) or ACE-I/ARB:
   • Sacubitril/valsartan (Entresto) preferred over ACE-I; reduces mortality, hospitalizations
   • ACE-I (enalapril, lisinopril) or ARB (valsartan, candesartan) if ARNI not tolerated
2. Beta-blockers:
   • Carvedilol, metoprolol succinate XL, bisoprolol
   • Start low, titrate up; contraindicated in acute decompensation
3. Mineralocorticoid receptor antagonists (MRA):
   • Spironolactone or eplerenone
   • Indicated if EF ≤35%, NYHA II-IV (watch K+, renal function)
4. SGLT2 inhibitors:
   • Dapagliflozin (DAPA-HF trial) or Empagliflozin (EMPEROR-Reduced)
   • Reduce HF hospitalizations and cardiovascular mortality regardless of diabetes status

• Diuretics: Loop diuretics (furosemide, torsemide) - symptom control, reduce congestion; no mortality benefit
• Ivabradine: If HR ≥70 bpm in sinus rhythm despite max beta-blocker; reduces HF hospitalizations
• Hydralazine + ISDN: For Black patients unable to tolerate RAAS blockade; mortality benefit
• Digoxin: Reduces HF hospitalizations; may control ventricular rate in AF
• Iron supplementation (IV ferric carboxymaltose): If iron-deficient (ferritin <100 or <300 + transferrin sat <20%)
• Omega-3 polyunsaturated fatty acids: Modest mortality benefit in stable CHF

HFpEF (EF ≥50%):

• Treat underlying causes: HTN, AF, obesity, diabetes, coronary disease
• SGLT2 inhibitors (empagliflozin, dapagliflozin) - proven benefit in HFpEF
• Diuretics for symptom control
• MRA (spironolactone) - possible benefit in HFmrEF/HFpEF
• ARNI - benefit in HFpEF with lower EF range (41-55%)

Device Therapy:

Advanced Heart Failure Therapies:

• LVAD (Left Ventricular Assist Device): Bridge to transplant or destination therapy; LVEF <25%, INTERMACS 1-4
• Heart transplantation: Gold standard for end-stage HF; VO2 max <14 mL/kg/min; limited by donor availability
• Inotropic support (IV dobutamine/milrinone): For acute decompensation; bridge to transplant/LVAD

Lifestyle & Non-pharmacologic:

• Sodium restriction: <2 g/day
• Fluid restriction: 1.5-2 L/day in advanced HF
• Daily weight monitoring: Alert for >2 kg gain in 2 days
• Exercise cardiac rehabilitation: Improves functional capacity and quality of life (HF-ACTION trial)
• Smoking cessation, alcohol abstinence
• Vaccination: Annual influenza, pneumococcal, COVID-19

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References: All content sourced from Harrison's Principles of Internal Medicine, 22nd Edition (2025, McGraw Hill Medical), Chapters 133 (Infective Endocarditis), 261-262 (Arrhythmias/Cardiomyopathy), 264 (Heart Failure), 266 (Classification of Cardiomyopathy), 267 (Genetic Cardiomyopathies), and 268 (Myocarditis).All nine questions have been answered comprehensively. Here is a summary of what was covered:

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Summary of Topics Covered

• Definition, morphologic classification (HCM/DCM/RCM/ARVC)
• Primary vs secondary causes (with full table of systemic diseases)
• Two-hit genetic model of pathogenesis
• General diagnostic workup (Harrison's Ch. 266, p. 2045)

• Genetics (1 in 500; sarcomere mutations - MYH7, MYBPC3)
• Dynamic LVOT obstruction mechanism, SAM, hemodynamics
• Clinical features (murmur behavior, S4, bifid pulse)
• Treatment: beta-blockers, verapamil, disopyramide, mavacamten (new FDA-approved myosin inhibitor)
• Surgical: myectomy vs alcohol septal ablation; ICD for sudden death risk

• Genetic (titin, lamin A/C) and acquired causes
• Heart failure syndrome presentation + echo/MRI findings
• Four-pillar GDMT: ARNI, beta-blocker, MRA, SGLT2i
• ICD, CRT, transplant indications

• ATTR amyloidosis (tafamidis - FDA-approved), endomyocardial fibrosis, Fabry, sarcoidosis
• Key distinction from constrictive pericarditis (table)
• Treatment of underlying disease

• Vegetation pathology, acute vs subacute, NVE/PVE/CIED-IE
• Duke-ISCVID 2015 criteria (major/minor, definite/possible/rejected)
• Antibiotic regimens by organism
• Surgical indications (HF, uncontrolled infection, embolic risk, abscess)

• RAAS, SNS, natriuretic peptide axes
• HFrEF/HFmrEF/HFpEF by EF; ACC/AHA stages A-D; NYHA I-IV

• Detailed symptom complex (LV vs RV failure symptoms)
• Physical exam findings (S3, JVP, crackles, pulsus alternans)
• Labs (BNP/NT-proBNP, troponin, iron studies)
• Instruments (echo, MRI, RHC, CXR with Kerley B lines)
• GDMT treatment with device therapy and advanced options