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Harrison's Cardiology - Detailed Topic-by-Topic Guidelines

Source: Harrison's Principles of Internal Medicine, 22nd Ed. (2025, McGraw Hill)

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TOPIC 1: HEART FAILURE (HF)

Definition & Epidemiology

Classification

Pathophysiology

• Systolic HF: Reduced contractility → reduced stroke volume → compensatory neurohormonal activation (RAAS, SNS) → maladaptive remodeling
• Diastolic HF: Impaired relaxation/filling → elevated filling pressures → pulmonary congestion

Clinical Features

• Dyspnea (exertional, then at rest, orthopnea, PND)
• Fatigue and reduced exercise tolerance
• Fluid retention: peripheral edema, ascites, raised JVP
• Pulmonary crepitations, S3 gallop, displaced apex beat

Diagnosis

• ECG: LVH, prior MI, LBBB (dyssynchrony)
• Echo: Gold standard - EF%, wall motion, diastolic function grade
• BNP/NT-proBNP: elevated in fluid overload (BNP >100 pg/mL diagnostic)
• CXR: cardiomegaly, pulmonary vascular congestion, Kerley B lines

Management - HFrEF (evidence-based pillars)

1. ACE inhibitor / ARB - reduce mortality (e.g., enalapril, ramipril, losartan)
2. Beta-blockers - carvedilol, bisoprolol, metoprolol succinate - reduce sudden death
3. Mineralocorticoid Receptor Antagonist (MRA) - spironolactone/eplerenone - reduces mortality post-MI with EF <40%
4. ARNI (Sacubitril/Valsartan) - replaces ACEI in stable HFrEF; superior to enalapril (PARADIGM-HF)
5. SGLT2 inhibitors - dapagliflozin/empagliflozin - reduce HF hospitalization and CV death (now proven in both HFrEF and HFpEF)
6. Diuretics - loop diuretics (furosemide) for symptom relief, not proven to reduce mortality
7. CRT - for LBBB with QRS >150 ms and EF <35%
8. ICD - EF <35% despite optimal therapy ≥3 months

Acute Decompensated HF

• IV furosemide (loop diuretic) - cornerstone for congestion
• IV nitroglycerin/isosorbide - preload reduction via venodilation (advantage: no plasma volume loss)
• Avoid hypoxemia; maintain SpO2 >95%
• Inotropes (dobutamine, milrinone) - for low-output/cardiogenic shock
• ACE inhibitors: ideal long-term after STEMI with LV dysfunction

HFpEF Management

• Control BP, HR, fluid status
• SGLT2i (empagliflozin shown to reduce hospitalization in EMPEROR-Preserved trial)
• Diuretics for symptom relief
• Spironolactone: modest benefit in selected patients

Cardiogenic Shock

• Incidence ~7% post-STEMI (down from 20% with prompt reperfusion)
• 90% develop in-hospital (not on admission)
• Requires inotropic support + mechanical circulatory support (IABP, Impella, VA-ECMO)

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TOPIC 2: CORONARY ARTERY DISEASE (CAD) & ACUTE CORONARY SYNDROMES (ACS)

Definition

Risk Factors

• Non-modifiable: age, male sex, family history, genetics
• Modifiable: hypertension, dyslipidemia, diabetes, smoking, obesity, sedentary lifestyle

Diagnosis of CAD - Imaging (Harrison's Table 248-3)

• Coronary CTA: best for excluding CAD in low-intermediate pretest probability
• Stress imaging preferred over ETT alone in: women, LBBB, inability to exercise, diabetics with intermediate-high risk
• 2021 ACC/AHA Chest Pain Guidelines: Class I for both coronary CTA AND stress imaging in symptomatic patients without prior CAD

STEMI (ST-Elevation MI)

• Morphine (if pain uncontrolled)
• Oxygen (if SpO2 <90%)
• Nitrates (not in RV infarction or BP<90)
• Aspirin 300 mg loading

• Primary PCI - gold standard (preferred if available within 60-90 min)
• Thrombolysis - if PCI not available within 120 min (tenecteplase, streptokinase)

• Beta-blocker, ACE inhibitor, statin, aspirin, P2Y12 for 1 year (minimum)
• ACE inhibitors: "ideal" for LV dysfunction post-MI (esp. long-term)
• Digitalis: benefits "unimpressive" post-STEMI (Harrison's specific note)

RV Infarction

• Seen in ~1/3 of inferior MI
• Clinical: JVD + Kussmaul's sign + hypotension WITHOUT pulmonary edema
• ST elevation in V4R (right-sided leads)
• Treatment: volume expansion (NOT diuretics) to maintain RV preload

NSTEMI/UA

• No ST elevation; troponin positive (NSTEMI) or negative (UA)
• Risk stratification by TIMI or GRACE score
• Antiplatelet + anticoagulation; early invasive strategy for high-risk
• Avoid nitrates in phosphodiesterase inhibitor users

Stable CAD

• Medical therapy first (ISCHEMIA trial 2020): optimal medical therapy comparable to early invasive strategy for most stable CAD with moderate/severe ischemia
• Medical: aspirin, statin (high-intensity), beta-blocker, ACEI/ARB, nitroglycerin PRN
• Revascularization indicated for: left main disease, proximal LAD, 3-vessel disease with LV dysfunction, refractory symptoms

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TOPIC 3: HYPERTENSION

Classification (ACC/AHA 2017)

Primary (Essential) Hypertension (~90% of cases)

1. Poor diet quality
2. Excess body weight / obesity
3. Excessive sodium intake (nearly all adults exceed WHO limits)
4. Insufficient potassium intake
5. Physical inactivity (>25% of US adults report none)
6. Alcohol consumption

Secondary Hypertension (~10% of cases)

Target Organ Damage

• LVH, retinopathy, microalbuminuria, proteinuria, CKD
• Stroke, CAD, PVD, HF, aortic dissection

Treatment

• DASH diet (low sodium, high potassium, low fat)
• Weight loss (1 mmHg per 1 kg lost)
• Aerobic exercise ≥150 min/week
• Limit alcohol
• Stop smoking

• General adults: <130/80 mmHg (ACC/AHA 2017)
• CKD with proteinuria: <130/80

• 80 years old: <150/90 (ESC) or <150 systolic (ACP); individualize

• SPRINT trial: intensive SBP target <120 mmHg reduced CV events but excluded diabetics, prior stroke, severe comorbidities

• Urgency: >180/120 without end-organ damage → oral labetalol, amlodipine, reduce BP over 24-48h
• Emergency: >180/120 WITH end-organ damage → IV labetalol/nicardipine/sodium nitroprusside; reduce MAP by no more than 25% in first hour

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TOPIC 4: ARRHYTHMIAS

Sinus Arrhythmias

• Sinus arrhythmia: P-P variation >120 ms; usually physiologic; types: respirophasic, ventriculophasic, non-phasic
• Sinus tachycardia (>100 bpm): sympathetic stimulation/vagal withdrawal; must identify and treat underlying cause
• Sinus bradycardia (<60 bpm): normal in athletes/sleep; sick sinus syndrome if symptomatic

Supraventricular Tachycardias (SVTs)

1. AVNRT - most common SVT; reentry within AV node; narrow complex, retrograde P waves
2. AVRT (WPW) - accessory pathway; delta wave on ECG; risk of AF→VF if accessory pathway has short refractory period
3. Atrial Flutter - 2:1 or 4:1 block; saw-tooth baseline; rate ~150 (with 2:1 block)
4. Atrial Tachycardia - focal or multifocal; abnormal P-wave morphology

• Vagal maneuvers → IV adenosine (6 mg, then 12 mg)
• If WPW: avoid adenosine/verapamil (can accelerate conduction); use procainamide
• Rate control: metoprolol, verapamil, diltiazem

Atrial Fibrillation (AF)

1. Rate control (HR <80 resting): beta-blockers, non-DHP CCBs, digoxin
2. Rhythm control (for symptomatic/young patients): cardioversion (electrical or pharmacologic), antiarrhythmics (flecainide, propafenone for no structural disease; amiodarone for structural heart disease), catheter ablation
3. Anticoagulation for stroke prevention:
   • CHA₂DS₂-VASc score ≥2 (men) or ≥3 (women): anticoagulate
   • DOACs (apixaban, rivaroxaban, dabigatran) preferred over warfarin
   • Assess bleeding risk with HAS-BLED score

Ventricular Arrhythmias

• Very common; usually benign in structurally normal hearts
• High burden (>20% of beats) can cause PVC-induced cardiomyopathy
• Indications for treatment: symptomatic, high burden causing LV dysfunction
• Treatment: beta-blockers, catheter ablation for focal PVCs

• Sustained VT (>30 seconds or requires termination): serious, requires evaluation
• Structural heart disease most common underlying cause (prior MI, cardiomyopathy)
• Management: acute - IV amiodarone, lidocaine, DC cardioversion; chronic - ICD, catheter ablation

• Disordered activation, no identifiable QRS
• Mechanism: spiral wave reentry/multiple circulating wavefronts
• Treatment: immediate defibrillation (ACLS protocol)
• If resuscitated without reversible cause: ICD implantation

• EF ≤35% despite optimal medical therapy ≥3 months
• NYHA class II-III HF
• Hypertrophic Cardiomyopathy: ICD for high-risk features (wall thickness >3 cm, prior syncope, NSVT, BP failure to rise with exercise, family history of SCD)
• Genetic dilated CMP: Lamin A/C or SCN5A mutations with EF <35%

• Surgical cryoablation for refractory VT (usually combined with aneurysmectomy)
• Used as adjunct to ventricular assist device implantation

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TOPIC 5: VALVULAR HEART DISEASE

Overview

• Cardiac murmur on examination
• Unexplained dyspnea
• Syncope or presyncope
• Preoperative assessment for bypass surgery

Aortic Stenosis (AS)

• No medical therapy proven to halt progression
• Surgical Aortic Valve Replacement (SAVR): standard for low-surgical-risk patients
• TAVI/TAVR (Transcatheter Aortic Valve Implantation): now indicated for all risk levels; preferred for high and intermediate surgical risk
• Timing: when symptomatic OR EF <50% OR undergoing other cardiac surgery

Aortic Regurgitation (AR)

Mitral Stenosis (MS)

• Rate control (beta-blocker, CCB) for AF
• Anticoagulation if AF or prior embolism
• Percutaneous Mitral Balloon Commissurotomy (PMBC): preferred for pliable, non-calcified valve without MR
• Surgical repair/replacement when PMBC not feasible

Mitral Regurgitation (MR)

• Symptomatic severe MR: surgical mitral valve repair preferred over replacement
• Asymptomatic severe primary MR with EF <60% or LVESD >40 mm: surgery
• Secondary MR: treat underlying HF; MitraClip for high-risk surgical patients (COAPT trial criteria)

Mitral Valve Prolapse (MVP)

• Most common valvular abnormality (~2-3% of population)
• Usually benign; rarely associated with MR or sudden death (arrhythmic MVP syndrome)
• Mid-systolic click ± late systolic murmur

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TOPIC 6: CARDIOMYOPATHIES

Hypertrophic Cardiomyopathy (HCM)

• Most common genetic cardiovascular disorder - 1 in 500 individuals
• Leading cause of sudden death <35 years in athletes
• Genetics: Autosomal dominant; sarcomere protein gene mutations (MYH7, MYBPC3 most common)

• Age <30
• LV wall thickness >3 cm
• Non-sustained VT on Holter
• Failure of BP to rise ≥20 mmHg with exercise
• Recent syncope (within 6 months)
• Family history of SCD from HCM
• LV apical aneurysm
• Massive LGE on CMR

• Medical: Beta-blockers, non-DHP CCBs (verapamil) - reduce symptoms of obstruction
• Mavacamten (cardiac myosin inhibitor) - new approved drug for obstructive HCM
• Disopyramide: for refractory obstruction
• Septal reduction therapy:
  • Surgical myectomy: SCD rate <1%/year post-procedure (gold standard)
  • Alcohol septal ablation: SCD rate 1-5%/year; alternative for high surgical risk
• ICD: For high-risk patients (see above)

Dilated Cardiomyopathy (DCM)

• EF <40%, dilated LV without cause (ischemia, valvular disease)
• Genetic DCM: 30-40% of nonischemic DCM; Lamin A/C and SCN5A mutations especially associated with arrhythmia
• Inheritance: autosomal dominant, recessive, X-linked (Duchenne/Becker), mitochondrial
• Treatment: Same as HFrEF (GDMT) + ICD if EF <35%

Restrictive Cardiomyopathy (RCM)

• Stiff, non-compliant ventricles with preserved EF but severely impaired filling
• Causes: Amyloidosis (AL or ATTR), hemochromatosis, sarcoidosis, Fabry disease, radiation
• ATTR amyloidosis: tafamidis reduces CV mortality (ATTR-ACT trial); consider early diagnosis with Tc-99m pyrophosphate scan
• Hemodynamics: Elevated filling pressures, low-normal EF, diastolic dysfunction grade III/IV

Inflammatory Cardiomyopathy (Myocarditis)

• Causes: Viral (Coxsackie B, parvovirus B19, COVID-19), autoimmune, toxic (anthracyclines, clozapine), giant cell myocarditis
• Presentation: Chest pain, acute HF, arrhythmias; can mimic STEMI
• Diagnosis: Troponin elevation, diffuse ST changes, MRI with LGE in non-ischemic pattern
• Biopsy: Dallas criteria (lymphocytic infiltration + myocyte necrosis)
• Treatment: Supportive; immunosuppression for giant cell/eosinophilic myocarditis; avoid NSAIDs

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TOPIC 7: PERICARDIAL DISEASE

Acute Pericarditis

1. Pleuritic chest pain (relieved leaning forward)
2. Pericardial friction rub
3. New widespread ST elevation or PR depression
4. New/worsening pericardial effusion

• Stage I: Diffuse saddle-shaped ST elevation + PR depression
• Stage II: ST normalizes
• Stage III: T-wave inversions
• Stage IV: ECG normalization

• NSAIDs (ibuprofen 600-800 mg TID or aspirin) - first-line
• Colchicine (0.5 mg BD, 3 months) - added to reduce recurrence (COPE, ICAP trials)
• Restrict activity until asymptomatic + CRP normal
• Corticosteroids: only if NSAID/colchicine contraindicated (increase risk of recurrence if used inappropriately)
• Avoid anticoagulation in large effusion (risk of hemopericardium)

Cardiac Tamponade

• Compression of heart by pericardial fluid → impaired filling → reduced cardiac output
• Beck's Triad: hypotension + muffled heart sounds + raised JVP
• Pulsus paradoxus: fall in SBP >10 mmHg on inspiration (pathognomonic when >20 mmHg)
• ECG: Electrical alternans (alternating QRS axis/amplitude)
• Echo: RA/RV collapse in diastole, IVC plethora (>21 mm, non-collapsing)
• Treatment: Emergency pericardiocentesis (needle or surgical)

Constrictive Pericarditis

• Fibrotic, thickened, often calcified pericardium → impaired diastolic filling
• Causes: Prior pericarditis, cardiac surgery, radiation, TB (most common worldwide)
• Features: Kussmaul's sign, pericardial knock (early S3-like sound), "square root sign" on hemodynamic tracing
• Echo: Septal bounce, respiratory variation in mitral/tricuspid inflow
• CT/MRI: Pericardial thickness >4 mm (normal <2 mm)
• Treatment: Pericardiectomy (surgical stripping) - definitive; 5-10% operative mortality

Pericardial Effusion

• Causes: Any pericarditis cause, hypothyroidism, malignancy, post-procedure
• Echo classification: Small (<10 mm), moderate (10-20 mm), large (>20 mm)
• Management: Treat underlying cause; pericardiocentesis if large/tamponade/diagnostic need

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TOPIC 8: PERIPHERAL VASCULAR & AORTIC DISEASE

Peripheral Arterial Disease (PAD)

• I: Asymptomatic
• IIA: Intermittent claudication (>200 m)
• IIB: Intermittent claudication (<200 m)
• III: Rest pain
• IV: Ulcer/gangrene (critical limb ischemia)

• All patients: antiplatelet (aspirin/clopidogrel), statin (high-intensity), smoking cessation, BP control
• Supervised exercise therapy: as effective as revascularization for claudication
• Revascularization for critical limb ischemia or lifestyle-limiting symptoms: endovascular (angioplasty ± stent) or surgical bypass
• Cilostazol: PDE-3 inhibitor, improves claudication symptoms; avoid in HF

Aortic Aneurysm

• Normal aorta <3 cm; AAA = ≥3 cm (defined as >50% dilation)
• Risk factors: Male, age >65, smoking, family history, atherosclerosis
• Screening: One-time ultrasound for men aged 65-75 who have ever smoked (USPSTF Grade B)
• Surveillance: 3-3.9 cm - every 3 years; 4-4.9 cm - annual; ≥5 cm - semi-annual
• Repair: Elective when ≥5.5 cm (men) or ≥5.0 cm (women); or growth >0.5 cm/6 months; or symptomatic
• Methods: EVAR (endovascular) or open surgical repair

• Often involves root (Marfan, bicuspid AV), arch, or descending
• Marfan syndrome: FBN1 gene; repair when ≥5.0-5.5 cm (or ≥4.5-5.0 with rapid growth or family history of dissection)
• Loeys-Dietz syndrome: Consider repair at smaller diameters (≥4.5 cm)

Aortic Dissection

• Stanford A: Involves ascending aorta → surgical emergency
• Stanford B: Only descending aorta → usually medical management (unless complicated)

• CXR: widened mediastinum (>8 cm)
• CT aortography: gold standard (sensitivity/specificity >95%)
• TEE: alternative if CT not feasible; also shows AR, pericardial effusion
• Avoid: coronary angiography as first-line (delays definitive imaging)

• Type A: Emergency surgery (replace ascending aorta ± AVR ± coronary reimplantation)
• Type B uncomplicated: IV beta-blocker (esmolol/labetalol) + IV nitroprusside; target SBP 100-120 mmHg, HR <60 bpm
• Type B complicated (malperfusion, rupture, rapid expansion): TEVAR (thoracic endovascular aortic repair)

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QUICK SUMMARY TABLE - Harrison's Cardiology Key Drug Therapies

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