Heart Failure - Harrison's Principles of Internal Medicine, 22nd Edition (2025)

1. DEFINITION

• The older term "congestive heart failure" is less preferred because some patients present without volume overload signs.
• "Cardiomyopathy" and "LV dysfunction" are broader terms for myocardial structural/functional disorders that may lead to HF.

2. EPIDEMIOLOGY

• ~6.7 million American adults are treated for HF; >600,000 new cases/year
• Globally, an estimated 56.2 million people have HF
• 5-year survival ~50% in primary care; 1-year mortality up to 40% in severe HF
• 1 in 8 deaths in the US lists HF on the death certificate
• Racial disparities: Black individuals have the highest risk, followed by Hispanic, White, and Chinese Americans - attributed to cardiometabolic risk factors and social determinants of health

3. PHENOTYPES / CLASSIFICATION

• Stage A: At risk (no symptoms, no structural disease)
• Stage B: Asymptomatic ventricular dysfunction
• Stage C: Symptomatic HF (most patients)
• Stage D: Advanced/refractory HF - salvage therapies needed

• Chronic HF: Longstanding (months to years) symptoms on therapy; episodes that resolve termed "remission" (not "stable"), since risk for decompensation/sudden death persists
• Acute HF (ADHF): Rapid onset or worsening of HF symptoms; ~80% represent worsening chronic HF, ~20% are new-onset (ACS, acute valvular dysfunction, hypertensive urgency, postcardiotomy)

4. PATHOPHYSIOLOGY

4a. Progressive Disease Model (HFrEF)

• Index event: acute (MI), gradual (pressure/volume overload), inherited (genetic cardiomyopathy), or congenital
• Patients may be asymptomatic for prolonged periods due to compensatory mechanisms that ultimately contribute to disease progression

4b. Ventricular Remodeling

• Myocyte hypertrophy and interstitial fibrosis
• Alterations in calcium-handling and cytoskeletal protein function
• Reexpression of fetal genes
• Cell loss via necrosis and apoptosis
• Afterload mismatch from systemic vasoconstriction + neurohormonal failure

4c. HFpEF Pathophysiology

5. SYMPTOMS

• Dyspnea on exertion - most common early symptom; caused by elevated pulmonary venous pressure
• Orthopnea - dyspnea in recumbent position; quantified by number of pillows used
• PND (paroxysmal nocturnal dyspnea) - awakens patient 1-3 hours after sleep; relieved by sitting up
• Bendopnea - dyspnea on bending forward (elevated filling pressures)
• Fatigue and weakness - from decreased cardiac output and peripheral hypoperfusion
• Nocturia - improved CO in supine position increases renal perfusion + delayed diuretic effect
• Oliguria - sign of advanced HF (severe reduction in renal blood flow)
• Mood disturbances and poor sleep - exacerbated by nocturnal dyspnea and sleep apnea
• Cardiac cachexia - unintentional weight loss; sign of advanced/poor prognosis

6. PHYSICAL EXAMINATION

General

• Mild-moderate HF: Well nourished, comfortable at rest; dyspnea on exertion
• Severe HF: Must sit upright, anxious, diaphoretic, dyspneic at rest; pallor (anemia) or duskiness (low output); cool extremities, peripheral cyanosis

Key Signs

7. PRECIPITATING FACTORS (Table 264-5)

8. DIAGNOSIS

Biomarkers

• BNP/NT-proBNP: Gold standard biomarkers; elevated in HF from volume/pressure overload; used for diagnosis, prognosis, and monitoring
• Cardiac troponins: Elevated in ADHF; associated with worse outcomes

Electrocardiogram

• No specific diagnostic pattern for HF
• LVH + left atrial enlargement → HFpEF from HTN, AS, HCM
• Q waves → ischemic cardiomyopathy
• Pseudo-infarct pattern (Q waves + reduced QRS voltage) → restrictive/infiltrative (amyloid)
• Conduction disease → cardiac sarcoid or Chagas cardiomyopathy
• AF present in up to 40% of chronic HF patients
• QRS width and LBBB guide CRT/pacing eligibility

Echocardiography (key noninvasive tool)

• LVEF ≥50% = systolic function normal
• Myocardial strain (speckle tracking) adds prognostic value
• Doppler estimates CO, PA pressures, valve areas, diastolic dysfunction
• TEE/CT: rule out LAA thrombus before cardioversion; assess valve pathology for TAVR/repair

Cardiac MRI

• Best for quantitative LV mass, volumes, function
• Defines specific etiology: ischemic CM, myocarditis, amyloidosis, hemochromatosis
• Late gadolinium enhancement (LGE) patterns guide diagnosis

Cardiopulmonary Exercise Testing (CPET)

• Used in evaluation for MCS or heart transplant
• Key parameters: peak VO2 and VE/VCO2 slope (independent predictors of survival)

Independent Predictors of Adverse Outcome (Table 264-1)

• Male sex, older age, diabetes mellitus, CKD, CAD, advanced NYHA class
• Presence of S3 or elevated JVP
• Decreased exercise capacity, cardiac cachexia
• Low LVEF, low sodium, elevated BNP/troponin, renal impairment

9. MANAGEMENT

9a. HFrEF (LVEF ≤40%) - The "Four Pillars"

9b. HFpEF/HFmrEF (LVEF ≥41%)

• Historically symptom-focused; management of comorbidities (obesity, DM, sleep apnea, HTN, AF, anemia, CKD)
• SGLT-2 inhibitors now have evidence to reduce CV mortality and HF hospitalizations in HFmrEF and HFpEF
• GLP-1 agonists and angiotensin-neprilysin inhibitors: emerging favorable results
• RAAS antagonists and MRA show variable benefits; principally in those with LVEF <60%

9c. Acute Decompensated HF (ADHF) Management

1. Hypertensive ADHF: High BP, pulmonary congestion → vasodilators (nitrates, nitroprusside)
2. Normotensive ADHF: Congestion without hypotension → IV diuretics (furosemide)
3. Low-output ADHF/Cardiogenic shock: Hypotension, hypoperfusion → inotropes, vasopressors, MCS

• Dobutamine: 2-20 μg/kg/min; variable efficacy with beta-blockers
• Milrinone: 0.375-0.75 μg/kg/min; reduce dose in renal insufficiency
• Levosimendan: 0.1 μg/kg/min; retains efficacy in presence of beta-blockers

• Nitroglycerin: 10-200 μg/min (often underdosed)
• Nitroprusside: 0.3-5 μg/kg/min; requires arterial line; caution thiocyanate toxicity in renal failure
• Nesiritide: 2 μg/kg bolus + 0.01 μg/kg/min infusion; hypotension risk

• BUN >43 mg/dL, SBP <115 mmHg, creatinine >2.75 mg/dL, elevated BNP/troponins

9d. Device Therapy

• ICD (Implantable Cardioverter-Defibrillator): Sudden cardiac death prevention in HFrEF
• CRT (Cardiac Resynchronization Therapy): For LBBB with wide QRS; improves symptoms and mortality
• His bundle / LBBP pacing: Emerging alternative to CRT

9e. Advanced/Stage D HF

• Cardiac transplantation: Gold standard for eligible patients
• LVAD (Mechanical Circulatory Support): Bridge to transplant or destination therapy
• Palliative care: Appropriate when salvage therapies are exhausted

9f. Surgical Therapy (selected indications)

• Coronary revascularization (for ischemic HF)
• Valvular repair/replacement (mitral, aortic)
• Transcatheter valve procedures (TAVR, MitraClip)

10. SUMMARY TABLE: HF EF-Based Management