Congestive Heart Failure (CHF) - MBBS Medicine Notes

1. DEFINITION

• HFrEF (Heart Failure with Reduced Ejection Fraction): EF < 40% - systolic dysfunction
• HFpEF (Heart Failure with Preserved Ejection Fraction): EF ≥ 50% - diastolic dysfunction
• HFmrEF (Mid-Range): EF 40-49%

2. EPIDEMIOLOGY

• Affects ~26 million people worldwide
• Prevalence increases sharply with age
• In industrialized countries, coronary artery disease (CAD) accounts for 60-75% of HF cases
• 5-year mortality remains >50%; worse than many cancers
• Framingham Study: Median survival was 1.7 years (men) and 3.2 years (women) after diagnosis
• Only 25% of men and 38% of women survived 5 years

3. ETIOLOGY

Most Common Causes (Industrialized Countries)

Other Causes

• Hypertrophic/restrictive cardiomyopathy
• Congenital heart disease
• Arrhythmias (AF, severe bradycardia)
• High-output states: anemia, thyrotoxicosis, AV fistula, Paget disease, beriberi
• Toxins: alcohol, anthracyclines, cobalt
• Genetic: mutations in cytoskeletal proteins (desmin, vinculin), nuclear membrane (lamin), inherited in autosomal dominant fashion; also Duchenne/Becker muscular dystrophies

4. PATHOPHYSIOLOGY

Compensatory Mechanisms (Frank-Starling & Neurohumoral)

4.1 Frank-Starling Mechanism

• Increased ventricular filling volume dilates the heart
• Greater actin-myosin cross-bridge formation increases stroke volume
• Compensated HF: Dilated ventricle maintains cardiac output
• Decompensated HF: Overloaded muscle can no longer maintain output; increased wall tension raises O2 demand on already-compromised myocardium

4.2 Neurohumoral Activation

1. Sympathetic Nervous System (SNS):
   • Releases norepinephrine → increased heart rate, contractility, and vascular resistance
   • Chronic activation leads to down-regulation of beta-receptors, cardiotoxicity, arrhythmias
2. Renin-Angiotensin-Aldosterone System (RAAS):
   • Angiotensin II → vasoconstriction, aldosterone release → Na+/H2O retention → increased preload and afterload
   • Angiotensin II also promotes myocyte hypertrophy and fibrosis
   • Renal angiotensin II increases 1000-fold in HF
3. Atrial Natriuretic Peptide (ANP) / BNP:
   • Released in response to volume overload
   • Counteracts RAAS: causes natriuresis, diuresis, vasodilation
   • Clinically used as a biomarker (BNP, NT-proBNP)
4. Arginine Vasopressin (ADH):
   • Released despite hyponatremia in HF → free water retention → dilutional hyponatremia

4.3 Cardiac Remodeling (Pathological Hypertrophy)

• Pressure overload (e.g., hypertension, aortic stenosis): New sarcomeres added in parallel → concentric hypertrophy (increased wall thickness, normal chamber size)
• Volume overload (e.g., mitral regurgitation, ASD): New sarcomeres added in series → eccentric hypertrophy / dilation (increased chamber size)

• Reduced capillary/myocyte ratio → ischemia and metabolic reprogramming
• Altered gene expression: fetal isoforms re-expressed (slower myosin ATPase, altered Ca2+ handling via SERCA)
• Fibroblast proliferation → interstitial fibrosis → increased stiffness, arrhythmias, impaired conduction
• Cardiomyocyte death by apoptosis and necrosis
• Endothelial dysfunction: reduced NO production, increased ROS → vasoconstriction

4.4 Hemodynamic Consequences

• Decreased cardiac output → decreased renal perfusion → RAAS activation → Na+/H2O retention
• Increased preload → elevated filling pressures → pulmonary congestion (left-sided) and/or systemic congestion (right-sided)
• Increased afterload (vasoconstriction) → further reduction in cardiac output

5. CLASSIFICATION

ACC/AHA Staging (A-D) vs. NYHA Functional Class (I-IV)

Key point: ACC/AHA stages describe structural disease progression (cannot improve); NYHA classes describe functional capacity (can fluctuate with therapy).

6. CLINICAL FEATURES

6.1 Left-Sided Heart Failure

• Dyspnea on exertion - the cardinal symptom
• Orthopnea - dyspnea when lying flat (ask number of pillows needed); due to redistribution of fluid from lower extremities to pulmonary circulation
• Paroxysmal Nocturnal Dyspnea (PND) - patient wakes up 1-2 hours after sleep, gasps for air, relieved by sitting up; highly specific for HF
• Cardiac asthma - wheeze from bronchospasm due to pulmonary edema
• Cough - may be dry or produce pink frothy sputum in severe cases
• Fatigue and weakness - from reduced cardiac output
• Nocturia - increased renal perfusion when recumbent at night

• Tachycardia
• Pulsus alternans (alternating strong/weak pulses - indicates severe LV dysfunction)
• Displaced/laterally shifted apex beat (cardiomegaly)
• S3 gallop (protodiastolic) - pathognomonic of volume overload/HF; indicates reduced compliance and rapid ventricular filling
• S4 gallop (presystolic) - from atrial kick into a stiff ventricle; seen in diastolic dysfunction, hypertension, IHD
• Functional mitral regurgitation - from LV dilation
• Bilateral basal crackles (crepitations) on lung auscultation - from pulmonary edema
• Cheyne-Stokes respiration - in severe HF; from prolonged circulation time
• Signs of pleural effusion (usually right-sided or bilateral)
• Elevated JVP (if right-sided failure co-exists)

6.2 Right-Sided Heart Failure

• Peripheral edema
• Abdominal swelling (ascites)
• Anorexia, nausea (gut edema)
• Right upper quadrant discomfort (hepatomegaly)

• Elevated Jugular Venous Pressure (JVP) - key sign
• Hepatojugular reflux (abdominojugular test) - pressing on the liver causes sustained rise in JVP
• Hepatomegaly (congestive, tender, pulsatile in TR)
• Pitting edema of dependent parts (ankles, legs, presacral in bedridden patients)
• Ascites
• Pleural effusion (transudates, more right-sided)
• Splenomegaly (from portal hypertension)
• Congestive splenomegaly

6.3 Congestive (Biventricular) Heart Failure

• Combination of both left and right-sided features
• Most common end-stage presentation
• Features: gross peripheral edema + pulmonary congestion + massively elevated JVP + cardiomegaly

7. INVESTIGATIONS

7.1 Electrocardiogram (ECG)

• Left bundle branch block (LBBB) - common in DCM
• LV hypertrophy (in hypertensive HF, AS)
• Q waves (prior MI)
• AF (common trigger/comorbidity)
• Non-specific ST-T changes
• Low voltage (in restrictive cardiomyopathy, amyloidosis)
• A normal ECG makes HF unlikely

7.2 Chest X-Ray (CXR)

• A - Alveolar edema ("bat wing" shadowing around hila)
• B - Kerley B lines (horizontal lines at lung bases - interstitial edema)
• C - Cardiomegaly (CTR > 0.5)
• D - Dilated upper lobe veins (cephalization of blood vessels - upper lobe veins larger than lower)
• E - Effusion (pleural, usually right-sided first)
• Fluffy perihilar shadowing (pulmonary edema)

7.3 Echocardiography (Key Investigation)

• Most important investigation - assesses:
  • LV/RV size and function
  • Ejection fraction (EF): Normal ≥ 55%
  • Wall motion abnormalities (IHD)
  • Valvular structure and function
  • Pericardial disease
  • Diastolic dysfunction (filling patterns: E/A ratio, deceleration time)
  • Differentiates HFrEF from HFpEF

7.4 Biomarkers

• Released from ventricular myocytes in response to increased wall stress
• BNP < 100 pg/mL: HF diagnosis unlikely
• BNP > 400 pg/mL: HF diagnosis likely; supports further workup
• BNP 100-500 pg/mL: Indeterminate zone
• NT-proBNP: longer half-life, higher values, adjusted for age (< 300 pg/mL rules out; age-specific cut-offs for rule-in)
• Useful for: diagnosis, severity assessment, prognosis, monitoring treatment response
• Elevated in: PE, pulmonary hypertension, renal failure, sepsis, AF (false positives)

7.5 Blood Tests

• CBC: Anemia (common comorbidity, worsens HF)
• Serum electrolytes: Hyponatremia (poor prognosis), hypo/hyperkalemia
• Renal function (BUN, creatinine, eGFR): Cardiorenal syndrome; renal impairment predicts mortality
• Liver function tests: Congestive hepatopathy
• Thyroid function (TFT): Hypo/hyperthyroidism can cause HF
• Fasting glucose / HbA1c: Diabetes - major risk factor
• Iron studies (Ferritin, TSAT): Iron deficiency common even without anemia; defined as Ferritin < 100 µg/L or Ferritin 100-299 µg/L + TSAT < 20%
• Lipid profile
• Troponin (if acute decompensation / ACS suspected)

7.6 Other Investigations

• 6-minute walk test / Cardiopulmonary exercise test (CPET): Functional capacity, VO2 max
• Cardiac MRI: Gold standard for myocardial tissue characterization (fibrosis, infiltration, myocarditis)
• Coronary angiography: If IHD suspected
• Right heart catheterization (Swan-Ganz): For hemodynamic assessment in advanced HF, before transplant/MCS
• Holter monitor: Arrhythmia detection

8. MANAGEMENT

8.1 General / Non-Pharmacological

• Salt restriction: < 2-3 g/day sodium
• Fluid restriction: ~1.5-2 L/day in symptomatic HF
• Daily weight monitoring: Alert if gaining > 2 kg in 2 days
• Exercise rehabilitation: Improves functional capacity in stable HF
• Smoking cessation, alcohol limitation
• Vaccination: Annual influenza, pneumococcal
• Address reversible precipitating factors: Infections, arrhythmias (AF), uncontrolled hypertension, medication non-compliance, NSAIDs (cause Na+ retention, blunt diuretic response), anemia, thyroid disease

8.2 Pharmacological Management of HFrEF

A. DIURETICS - for Fluid Overload (Symptomatic Relief)

• Furosemide - 20-40 mg OD/BD (up to 600 mg/day); duration 6-8 hours
• Bumetanide - 0.5-1 mg OD/BD
• Torsemide - 10-20 mg OD; longer duration (12-16 hrs), better oral bioavailability
• Mechanism: Block Na+/K+/2Cl- cotransporter in thick ascending limb of Loop of Henle
• Side effects: Hypokalemia, hyponatremia, ototoxicity, hypomagnesemia, gout

• Metolazone (2.5-5 mg), Hydrochlorothiazide
• Added to loop diuretics in resistant edema

• Spironolactone / Eplerenone
• (Discussed further below as disease-modifying agents)

• Tolvaptan - for hypervolemic/euvolemic hyponatremia in HF
• Aquaresis without natriuresis

B. NEUROHORMONAL BLOCKADE - Disease-Modifying Therapy (Reduce Mortality)

• Drugs: Enalapril, Lisinopril, Ramipril, Captopril
• Mechanism: Block conversion of Angiotensin I → II → reduce vasoconstriction, aldosterone, preload, afterload; inhibit cardiac remodeling
• Benefits: Reduce mortality 20-25%, improve symptoms, reverse remodeling
• Start low, titrate to target doses
• Monitor: Creatinine, K+ (risk of hyperkalemia)
• Contraindications: Bilateral renal artery stenosis, pregnancy, angioedema, K+ > 5.5 mEq/L
• Side effect: Dry cough (due to bradykinin accumulation) - switch to ARB

• Drugs: Losartan, Valsartan, Candesartan, Sacubitril
• Used when ACEi is not tolerated (especially cough)
• Similar mortality benefit to ACEi
• Less bradykinin-mediated effects (no cough)

• Drug: Sacubitril/Valsartan (Entresto)
• Mechanism: Valsartan (ARB) + Sacubitril (neprilysin inhibitor) → blocks breakdown of natriuretic peptides (ANP, BNP) → enhanced natriuresis + vasodilation + anti-remodeling
• Superior to ACEi alone (PARADIGM-HF trial): 20% reduction in CV death/HF hospitalization
• Do not combine with ACEi (risk of angioedema); wash out period of 36 hours required
• First-line preferred over ACEi in symptomatic HFrEF patients who can tolerate it

• Drugs: Carvedilol (alpha + beta), Bisoprolol, Metoprolol succinate (extended release)
• These are the ONLY beta-blockers with proven mortality benefit in HF
• Mechanism: Reduce heart rate, block chronic sympathetic activation, reverse beta-receptor downregulation, reduce sudden cardiac death, reverse remodeling
• Benefits: Reduce mortality 34-35%, reduce hospitalizations, improve EF
• Start only in stable (euvolemic) patients - initiate at very low doses, titrate slowly
• DO NOT start in acutely decompensated HF (can precipitate acute decompensation)
• Side effects: Bradycardia, hypotension, fatigue, bronchospasm (use cardioselective BBs)

• Drugs: Spironolactone (25-50 mg/day), Eplerenone (more selective, less gynecomastia)
• Added in NYHA Class II-IV HFrEF with EF ≤ 35%
• Mechanism: Block aldosterone → reduce Na+ retention, reduce cardiac fibrosis and remodeling
• Benefit: 30% reduction in mortality (RALES trial - spironolactone; EMPHASIS-HF - eplerenone)
• Monitor K+ closely (risk of hyperkalemia, especially with ACEi/ARB)
• Contraindicated: K+ > 5.0 mEq/L, creatinine > 2.5 mg/dL

• Drugs: Dapagliflozin, Empagliflozin
• Originally antidiabetic drugs; now approved for HF (with or without diabetes)
• Mechanism: Reduce tubular glucose reabsorption → osmotic diuresis + natriuresis; direct cardiac effects (improved mitochondrial function, reduced inflammation)
• Benefits (DAPA-HF, EMPEROR-Reduced trials): Reduce HF hospitalization and CV death by ~25%; also stabilize renal function
• Well-tolerated; low risk of hypoglycemia and hyperkalemia
• The "fourth pillar" of HFrEF therapy (alongside ARNI/ACEi, BB, MRA)

• Drug: Ivabradine
• Mechanism: Inhibits HCN channel (If current) in SA node → reduces heart rate without affecting contractility
• Used in HFrEF (EF ≤ 35%) with resting HR ≥ 70 bpm on maximally tolerated BB, NYHA II-III, in sinus rhythm
• SHIFT trial: Reduced HF hospitalizations

• Combination vasodilator
• Particularly effective in Black/African American patients (A-HeFT trial: significant mortality reduction in this population)
• Used when ACEi/ARB/ARNI not tolerated (cough, angioedema, renal dysfunction)
• Mechanism: Hydralazine - arterial vasodilator (↓ afterload); Nitrate - venodilator (↓ preload)

• Mechanism: Inhibits Na+/K+ ATPase → increased intracellular Ca2+ → positive inotropy; also reduces sympathetic activation and slows AV conduction
• Used in HFrEF with AF (for rate control) or persistent symptoms on maximal therapy
• Reduces hospitalizations but NOT mortality (DIG trial)
• Narrow therapeutic index: target serum level 0.5-0.9 ng/mL
• Toxicity: Nausea, vomiting, visual disturbances (xanthopsia), arrhythmias (bigeminy, junctional tachycardia, heart block); worsened by hypokalemia/hypomagnesemia
• Avoid in: Hypertrophic obstructive cardiomyopathy, WPW syndrome

• Vericiguat (soluble guanylate cyclase stimulator): For high-risk HFrEF after decompensation
• Omecamtiv mecarbil (cardiac myosin activator): Still under investigation

Summary Table: "Quadruple Therapy" for HFrEF

8.3 Management of HFpEF

• Much more limited evidence compared to HFrEF
• No mortality benefit shown with ACEi, ARB, BB in HFpEF
• Management: diuretics for symptomatic congestion, control heart rate, treat underlying cause (BP, AF, ischemia)
• SGLT2 inhibitors (Empagliflozin - EMPEROR-Preserved trial): Reduce HF hospitalizations - first class to show benefit in HFpEF
• Spironolactone: TOPCAT trial showed borderline benefit, used in practice

8.4 Device Therapy

• Prevents sudden cardiac death (SCD) from ventricular arrhythmias
• Indicated in: EF ≤ 35%, NYHA class II-III, on optimal medical therapy for > 3 months
• Primary or secondary prevention of SCD

• Indicated in: EF ≤ 35%, LBBB with QRS ≥ 150 ms (or 120-150 ms with appropriate morphology), NYHA II-III
• Synchronizes LV-RV contraction → improves EF, symptoms, mortality

8.5 Management of Acute Decompensated Heart Failure (ADHF)

• L - Lasix (Furosemide IV) - IV loop diuretics urgently
• M - Morphine (low dose - reduces anxiety, venodilation) - controversial, now used less
• N - Nitrates (IV/SL GTN) - for pulmonary edema with normal/high BP; venodilation
• O - Oxygen - maintain SpO2 > 94%; NIV (BiPAP) if respiratory failure
• P - Position - sit upright, legs dependent

• Nitroglycerin (GTN), Sodium nitroprusside (for hypertensive emergency + pulmonary edema)
• Avoid if BP < 90 mmHg

• Dobutamine (beta-1 agonist - increases contractility without much vasoconstriction)
• Dopamine (low dose - renal vasodilation; higher doses - vasopressor)
• Milrinone (phosphodiesterase-3 inhibitor - inotropy + vasodilation)
• Use as bridge to definitive therapy; short-term only

8.6 Advanced/Refractory HF (Stage D)

• Ventricular Assist Devices (VAD): LVAD as bridge to transplant or destination therapy
• Cardiac Transplantation: Gold standard for end-stage HF; 50% survival at 10 years
• Criteria: NYHA IV, medically refractory, no other surgical options, adequate social support
• Contraindications: Irreversible pulmonary hypertension (PVR > 6 Wood units), active infection, malignancy, severe non-cardiac illness
• Palliative Care: Symptom management (opioids for dyspnea), hospice

9. COMPLICATIONS

10. PROGNOSIS

• Low EF (< 25%)
• NYHA Class IV
• Hyponatremia (Na+ < 130 mEq/L)
• Elevated BNP/NT-proBNP
• Elevated creatinine / low eGFR (cardiorenal syndrome)
• Presence of arrhythmias (VT, AF)
• Low peak VO2 on CPET (< 10 mL/kg/min)
• Frequent hospitalizations
• Lack of response to BB/ACEi

11. HIGH-YIELD EXAM POINTS

• Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, Chapters 48, 49, 50
• Robbins & Kumar Basic Pathology, Chapter 9 (Heart)
• Goodman & Gilman's The Pharmacological Basis of Therapeutics, Chapter 33
• Goldman-Cecil Medicine, Chapter on Heart Failure