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Congestive Heart Failure (CHF) - Complete MBBS Final Year Notes

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1. DEFINITION

• The ESC definition emphasizes cardinal symptoms (breathlessness, ankle swelling, fatigue) accompanied by signs (elevated JVP, pulmonary crackles, peripheral edema) due to structural/functional cardiac abnormality causing elevated intracardiac pressures and/or inadequate cardiac output at rest or during exercise.
• The term "congestive heart failure" is now largely replaced by "heart failure" because some patients present without volume overload.
• In pathophysiologic terms: HF = syndrome of elevated cardiac filling pressure and/or inadequate peripheral oxygen delivery, at rest or during stress, caused by cardiac dysfunction.

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2. EPIDEMIOLOGY

• Most common cause of hospitalization in adults >65 years.
• 5-year mortality ~50% overall; readmission within 6 months in ~50% of hospitalized patients.
• Costs: Estimated $22.3 billion in US (2018), projected to rise to $70 billion by 2030.

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3. ETIOLOGY AND CAUSES

HF with Reduced Ejection Fraction (HFrEF, EF ≤40%)

• Coronary artery disease (MI, ischemia) - most common cause in developed countries
• Valvular heart disease (aortic stenosis/regurgitation, mitral/tricuspid regurgitation)
• Nonischemic cardiomyopathy:
  • Infiltrative disorders (amyloidosis, sarcoidosis, hemochromatosis)
  • Familial/genetic cardiomyopathies
  • Tachycardia-induced cardiomyopathy
  • Toxic: chemotherapy, immunotherapy, drugs (hydroxychloroquine), alcohol
• Hypertension (can cause both HFrEF and HFpEF)

HF with Preserved Ejection Fraction (HFpEF, EF ≥50%)

High-Output Heart Failure (rare)

• Severe anemia, hyperthyroidism, AV fistula, Paget's disease, beriberi (thiamine deficiency)
• Normal/elevated CO with low SVR - seldom causes HF alone, but may precipitate it in underlying cardiac disease

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4. CLASSIFICATION

By Ejection Fraction (EF):

NYHA Functional Classification:

ACC/AHA Staging (by progression):

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5. PATHOPHYSIOLOGY

5a. Primary Hemodynamic Abnormalities

• Ventricular dysfunction → decreased cardiac output (CO) → activation of compensatory mechanisms
• Three determinants of myocardial performance: preload, afterload, and contractility

5b. Neurohormonal Activation (The Core Mechanism)

1. Sympathetic Nervous System (SNS):
   • Increased norepinephrine → tachycardia, vasoconstriction, increased contractility (short-term compensation)
   • Chronic activation → cardiac toxicity, myocyte apoptosis, progressive dysfunction
2. Renin-Angiotensin-Aldosterone System (RAAS):
   • Reduced renal perfusion → renin → Ang II → aldosterone
   • Angiotensin II → vasoconstriction + aldosterone release → sodium and water retention → volume overload
   • Long-term: maladaptive fibrosis, hypertrophy, remodeling
3. Arginine Vasopressin (ADH):
   • Elevated in HF → water retention → dilutional hyponatremia
4. Natriuretic Peptides (BNP, ANP) - Compensatory:
   • Released by myocardial stretch → natriuresis, vasodilation, anti-fibrotic
   • BNP/NT-proBNP are key diagnostic and prognostic biomarkers
5. Endothelin-1:
   • Potent vasoconstrictor; elevated in HF, correlates with severity
6. Inflammatory Cytokines:
   • TNF-α, IL-1, IL-6 → progressive cardiac dysfunction, cardiac cachexia

5c. Ventricular Remodeling

• Concentric hypertrophy: increased mass without chamber volume increase - pressure overload (hypertension, aortic stenosis) - reduces wall stress via Laplace's law
• Eccentric hypertrophy: increased chamber volume - volume overload (AR, MR) - eventually → dilation and systolic dysfunction
• Remodeling involves:
  • Myocyte hypertrophy + interstitial fibrosis
  • Altered calcium-handling proteins
  • Re-expression of fetal genes
  • Myocyte apoptosis and necrosis
  • Afterload mismatch → cycle of progressive dysfunction

5d. HFpEF Pathophysiology

• Impaired calcium reuptake into sarcoplasmic reticulum → delayed relaxation
• Increased passive myocardial stiffness from fibrosis/hypertrophy
• Microvascular inflammation, endothelial dysfunction
• Systemic inflammation (driven by comorbidities: obesity, DM, HTN)

5e. Cardiorenal Syndrome

• Reduced CO → decreased renal arterial perfusion AND elevated venous congestion → renal dysfunction
• Increased intra-abdominal pressure (right-sided HF) → renal vasoconstriction
• Splanchnic and hepatorenal reflexes worsen renal function
• Diuresis relieves both volume and abdominal pressure → improves renal function

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6. CLINICAL FEATURES

Symptoms:

Signs on Physical Examination:

• Mild-moderate HF: Well nourished and comfortable at rest
• Severe HF: Sits upright, anxious, diaphoretic, dyspneic at rest; cool extremities, peripheral cyanosis
• Cardiac cachexia: Unintentional edema-free weight loss >5% in 12 months (bitemporal wasting)
• Scleral icterus/jaundice: Severe right HF

• Tachycardia (new-onset), BP may be elevated early (sympathetic activation)
• Chronic HF on therapy: resting HR ideally <70-75 bpm; BP in normal-low-normal range
• Irregular rhythm (AF, premature complexes)
• Severe HF: low BP (cardiogenic shock), pulsus alternans

• Elevated JVP (>4 cm above sternal angle) indicates elevated right heart filling pressures
• Hepatojugular reflux: compress RUQ → JVP rises → indicates right heart failure

• Bilateral basal inspiratory crackles (pulmonary edema)
• Dullness at bases (pleural effusion)
• Wheezing ("cardiac asthma")

• Displaced apex beat (dilated LV)
• S3 gallop (protodiastolic): pathognomonic of LV dysfunction and elevated filling pressures
• S4 gallop (presystolic): impaired LV relaxation/stiffness (HFpEF)
• Murmurs (underlying valvular disease)
• Parasternal heave (right ventricular hypertrophy)

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

• Pitting edema (bilateral, dependent)
• Anasarca (severe HF)

• Reduced EF, reduced RV ejection fraction, elevated PCWP, reduced cardiac index, hyponatremia, elevated troponin/BNP, LBBB, AF, ventricular tachycardia

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7. PRECIPITATING FACTORS

• Patient-related: Dietary indiscretion (excess salt/fluid), medication non-compliance
• Cardiovascular: Myocardial ischemia/infarction, new arrhythmias (especially AF), pulmonary embolism
• Provider-related: NSAIDs, thiazolidinediones, TNF inhibitors, calcium channel blockers (negative inotropes), excessive IV fluids, cardiotoxic drugs
• Other systemic illness: Infections, worsening renal/hepatic failure, hyperthyroidism, anemia/iron deficiency, untreated sleep apnea

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8. INVESTIGATIONS

Routine Laboratories:

• BMP/CMP: Urea, creatinine (elevated in moderate-severe HF), electrolytes
  • Hyponatremia: diuretics + vasopressin-mediated water retention - negative prognostic indicator
  • Hypokalemia: loop/thiazide diuretics
  • Hyperkalemia: severe GFR reduction + RAAS inhibitors
• CBC: Anemia (common comorbidity, worsens HF)
• LFTs: Elevated transaminases, bilirubin (congestive hepatopathy); marked elevation + lactic acid → cardiogenic shock
• Thyroid function (to exclude thyroid causes)
• Urinalysis: Proteinuria (hypertension, diabetes)

Biomarkers:

• BNP (B-type natriuretic peptide) and NT-proBNP:
  • Elevated in HF proportional to filling pressures and symptoms
  • Best used to rule in/out HF in dyspneic patients; guides prognosis and therapy
  • Also elevated in: AF, PE, renal failure, sepsis
• Cardiac troponin I/T: Elevated in myocyte injury; predicts worse prognosis

12-Lead ECG:

• Detects: LVH, LBBB (indicates dyssynchrony), AF, ischemia/infarction, QRS prolongation
• LBBB + HF → indication for cardiac resynchronization therapy (CRT)

Chest X-Ray:

• Cardiomegaly (CTR >0.5)
• Pulmonary vascular redistribution (upper lobe diversion - "cephalization")
• Kerley B lines (horizontal, 1-2 cm at lung bases - interstitial edema)
• Pulmonary edema (bat-wing/perihilar haziness)
• Pleural effusions (typically bilateral, more on right)

Echocardiography (KEY Investigation):

• Most important single test in HF evaluation
• Two-dimensional echo with Doppler:
  • Measures LVEF (distinguishes HFrEF vs HFpEF)
  • Detects wall motion abnormalities, valvular disease, diastolic dysfunction (Grade I-IV)
  • Estimates pulmonary artery pressures
  • Assesses right ventricular function, pericardial disease
  • Detects thrombus, infiltrative disease

Other Investigations:

• Cardiac MRI: Gold standard for myocardial tissue characterization (inflammation, fibrosis, infiltration)
• Coronary angiography/CT coronary angiography: Rule out ischemic etiology
• Cardiac nuclear imaging (PET): Myocardial viability assessment before revascularization
• 6-minute walk test / Cardiopulmonary exercise testing (CPET): Objective functional capacity; VO2 max <14 mL/kg/min → indication for transplant evaluation
• Right heart catheterization (pulmonary artery catheter): Gold standard for hemodynamics; reserved for refractory HF, diagnostic uncertainty, pre-transplant/LVAD evaluation

Diagnostic Algorithm (Fig. 264-8 from Harrison's):

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9. MANAGEMENT

9a. General Principles and Non-Pharmacological Measures:

• Sodium restriction: <2-3 g/day
• Fluid restriction: 1.5-2 L/day in moderate-severe HF with hyponatremia
• Weight monitoring: Daily weights; contact physician if weight gain >2 kg in 2 days
• Aerobic exercise: Safe and beneficial in stable HF (NYHA I-III)
• Treat modifiable risk factors: BP control, diabetes management, dyslipidemia
• Avoid: NSAIDs, excessive alcohol, illicit drugs, negative inotropes (unless necessary)
• Vaccinations: Annual influenza, pneumococcal

9b. Pharmacological Management of HFrEF (Four Pillars - "Fantastic Four"):

• Block RAAS → vasodilation + reduced aldosterone
• ACEi: captopril, enalapril, ramipril, lisinopril
• ARB (if ACEi-intolerant): valsartan, candesartan, losartan
• Dose to target/maximum tolerated
• Reduce mortality and hospitalizations in all symptomatic HFrEF

• Block chronic SNS activation
• Evidence-based agents: carvedilol, bisoprolol, metoprolol succinate
• Start low, titrate slowly; avoid in acute decompensation
• Reduce mortality 30-35%; prevent sudden cardiac death

• Spironolactone, eplerenone (fewer androgenic side effects)
• Block aldosterone → reduce fibrosis, sodium retention
• Monitor K+ and creatinine carefully (hyperkalemia risk)
• Reduce mortality in NYHA II-IV with EF ≤35% (RALES, EPHESUS trials)

• Sacubitril/valsartan (Entresto)
• Combined neprilysin inhibition (↑ BNP, natriuresis) + AT1 blockade
• PARADIGM-HF trial: 20% relative risk reduction in cardiovascular death/HF hospitalization vs enalapril
• Now preferred over ACEi/ARB in patients who tolerate it
• Cannot combine with ACEi (risk of angioedema); washout 36 hours required

• Dapagliflozin, empagliflozin
• DAPA-HF trial: 26% reduction in worsening HF or CV death; independent of diabetes status
• EMPEROR-Reduced: 25% reduction in CV death or HF hospitalization
• Mechanism in HF: osmotic diuresis, natriuresis, reductions in preload/afterload, metabolic effects
• Now foundational therapy alongside ARNI, beta-blockers, and MRA ("four pillars")

• Loop diuretics (furosemide, torsemide, bumetanide): Symptom relief through decongestion; no mortality benefit but essential for quality of life
• Ivabradine: Inhibits If current in SA node → pure rate reduction; indicated when HR >70 bpm in sinus rhythm despite optimal beta-blocker; reduces HF hospitalization (SHIFT trial)
• Digoxin: Positive inotrope + rate control in AF; reduces HF hospitalizations (no mortality benefit); narrow therapeutic index; target level 0.5-0.9 ng/mL
• Hydralazine + Isosorbide dinitrate: Used if ACEi/ARB/ARNI not tolerated; particularly beneficial in Black patients (A-HeFT trial)
• Vericiguat: Soluble guanylyl cyclase stimulator; modest 10% relative risk reduction in CV death/HF hospitalization in high-risk HFrEF (VICTORIA trial)

9c. Management of Acute Decompensated HF (ADHF):

1. Identify and address precipitating factors
2. Hemodynamic optimization: relieve congestion, reduce afterload, maximize organ perfusion

• Warm + Wet (most common): IV diuretics ± vasodilators
• Cold + Wet (low output + congestion): Inotropes + diuretics
• Cold + Dry (cardiogenic shock): Vasopressors + mechanical support

• IV loop diuretics (furosemide IV 40-160 mg): Essential when oral therapy insufficient
• IV furosemide should be given at ≥ equivalent oral dose
• Ultrafiltration: Considered in diuretic resistance

• IV nitroglycerin: reduces preload (venodilation) and afterload
• IV nitroprusside: arterial + venous dilation; watch cyanide toxicity
• IV nesiritide (BNP): vasodilation; no mortality benefit

• Dobutamine (β1 agonist): positive inotropy; may worsen arrhythmias
• Milrinone (PDE-3 inhibitor): inotropy + vasodilation; use in beta-blocker-intolerant patients
• No long-term survival benefit; reserved as bridge therapy

• BUN >43 mg/dL
• SBP <115 mmHg
• Serum creatinine >2.75 mg/dL
• Elevated troponin/natriuretic peptides

9d. Device Therapy:

• Primary prevention: EF ≤35% despite 3+ months of optimal medical therapy; NYHA class II-III
• No benefit within 40 days of MI
• Principles: most benefit at early HF stages; sudden death incidence diminishes with advancing HF

• Indicated: EF ≤35% + LBBB + QRS ≥150 ms + NYHA class II-IV on optimal therapy
• Corrects ventricular dyssynchrony → improved CO, reverse remodeling
• CRT-D = CRT + ICD (preferred in eligible patients)

9e. Surgical Therapy:

• CABG: Ischemic cardiomyopathy with multivessel CAD + angina; long-term mortality benefit (STICH trial - 10-year benefit shown)
• Mitral valve repair/replacement: For functional MR with severe regurgitation despite medical therapy; transcatheter edge-to-edge repair (TEER/MitraClip) showing benefit
• Surgical ventricular restoration (SVR): Limited evidence for LVEF improvement; considered with LV aneurysm + refractory HF, arrhythmias, or thromboembolism
• Left Ventricular Assist Device (LVAD): Mechanical circulatory support for:
  • Bridge to transplantation
  • Destination therapy (in transplant-ineligible patients)
  • Bridge to recovery (in potentially reversible cardiomyopathies)
• Heart Transplantation: Definitive therapy for end-stage HF; 5-year survival >70%; limited by donor availability

9f. Management of HFpEF:

• No proven mortality-reducing pharmacotherapy until recently
• SGLT-2 inhibitors (empagliflozin - EMPEROR-Preserved; dapagliflozin - DELIVER): Reduce CV mortality/HF hospitalization - now recommended for HFmrEF and HFpEF
• Focus on: symptom control, diuretics (congestion), BP control, AF management, comorbidity treatment (obesity, DM, OSA)
• ARBs (candesartan - CHARM Preserved): reduced HF hospitalizations but no mortality benefit
• MRAs (spironolactone - TOPCAT): possible hospitalization reduction in Americas subgroup

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10. COMPLICATIONS

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11. PROGNOSIS

• Overall 5-year mortality ~50% (comparable to many cancers)
• NYHA Class IV: 1-year mortality >50%
• Poor prognosis indicators:
  • Low LVEF, elevated JVP, S3 gallop, cardiac cachexia
  • Hyponatremia, elevated creatinine, elevated BNP/troponin
  • AF, LBBB, ventricular tachycardia
  • NYHA Class III-IV
  • Low VO2 max on CPET
• Prognosis is improving with guideline-directed medical therapy (GDMT)

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12. QUICK MEMORY AIDS

• Class I - No limitation
• Class II - Slight limitation
• Class III - Marked limitation
• Class IV - Symptoms at Rest

• Beta-blocker
• ARNI (sacubitril/valsartan) or ACEi/ARB
• Mineralocorticoid receptor antagonist
• SGLT-2 inhibitor

• Pulmonary embolism
• Infection / Ischemia
• Rhythm disorders (AF)
• Anemia / Arrhythmia
• Thyroid dysfunction
• Endocarditis / fluid overload
• Salt/medication non-compliance

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PubMed Note: The 2022 AHA/ACC/HFSA Heart Failure Guidelines (Heidenreich et al., PMID 35379503) and the SGLT-2 inhibitor trials (DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved) are the most recent major evidence updates - all reflected in Harrison's 22nd edition content above.---

• Davidson's Principles & Practice of Medicine (very popular for MBBS in UK/India/South Asia)
• Harrison's Principles of Internal Medicine (the gold standard for MBBS final year globally)
• Kumar & Clark's Clinical Medicine

1. Definition - Universal HF definition (AHA/ACC/ESC), distinction from CHF
2. Epidemiology - Prevalence, incidence, lifetime risk, costs
3. Etiology - HFrEF vs HFpEF causes, high-output HF
4. Classification - EF-based types, NYHA functional classes I-IV, ACC/AHA stages A-D
5. Pathophysiology - Neurohormonal activation (SNS, RAAS, ADH, BNP, endothelin), ventricular remodeling, cardiorenal syndrome
6. Clinical Features - All symptoms with mechanisms, complete physical signs
7. Precipitating Factors - Mnemonic PIRATES
8. Investigations - Labs, BNP, ECG, CXR (Kerley B lines), Echo, advanced imaging
9. Management - Four pillars (Beta-blocker + ARNI + MRA + SGLT-2i), acute HF phenotypes, device therapy (ICD/CRT), surgical options, HFpEF management
10. Complications and Prognosis
11. Memory Aids for exams

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CONGESTIVE HEART FAILURE (CHF)

Comprehensive MBBS Final Year Notes

Sources: Harrison's 22nd Ed (2025) + Goldman-Cecil Medicine

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SECTION 1: DEFINITION

• The AHA/ACC/HFSA definition: "a complex clinical syndrome with symptoms and signs that result from any structural or functional impairment of ventricular filling or ejection of blood."
• The ESC definition emphasizes: cardinal symptoms (breathlessness, ankle swelling, fatigue) accompanied by signs (elevated JVP, pulmonary crackles, peripheral edema) due to structural/functional cardiac abnormality causing elevated intracardiac pressures and/or inadequate cardiac output at rest or during exercise.
• Pathophysiologic definition: a syndrome characterized by elevated cardiac filling pressure and/or inadequate peripheral oxygen delivery, at rest or during stress, caused by cardiac dysfunction.

Why "heart failure" not "congestive heart failure"? Because congestion is a common but NOT universal feature - some patients present without signs of volume overload. Hence the older term "congestive heart failure" (CHF) has been replaced by simply "heart failure" (HF) in modern guidelines.

Key Types:

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SECTION 2: EPIDEMIOLOGY

• Prevalence is increasing in younger and older individuals, and especially in those with preserved ejection fraction (HFpEF).
• Despite rising prevalence, temporal improvements in survival have occurred with guideline-directed medical therapy.

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SECTION 3: ETIOLOGY AND CAUSES

3a. Causes of HF (Goldman-Cecil Table 45-1):

Regional variation: Chagas cardiomyopathy is prevalent in Central/South America. Rheumatic valvular disease is common in developing countries but rare in developed nations.

3b. Causes of Right-sided HF:

• Most commonly: left-sided HF (commonest cause)
• Pulmonary thromboembolic disease
• Chronic lung disease (cor pulmonale)
• Pulmonary arterial hypertension
• Right ventricular infarction
• Tricuspid valve disease

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SECTION 4: CLASSIFICATION

4a. Classification by Ejection Fraction (EF):

4b. NYHA Functional Classification:

4c. ACC/AHA Staging (Disease Progression):

Key concept: Stage A→D describes disease progression; NYHA I→IV describes symptom severity. A patient can be Stage C, NYHA Class II. Both must be recorded.

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SECTION 5: PATHOPHYSIOLOGY

5a. Fundamental Concept:

5b. Neurohormonal Activation - The Central Mechanism:

1. Sympathetic Nervous System (SNS) Activation:

• Trigger: Reduced CO detected by baroreceptors
• Effects: ↑ Heart rate, ↑ myocardial contractility, peripheral vasoconstriction (maintains BP)
• Chronic maladaptation:
  • Myocardial norepinephrine toxicity → myocyte apoptosis
  • ↓ β1-receptor density and sensitivity (downregulation)
  • Promotes ventricular arrhythmias → sudden cardiac death
  • Increased afterload → worsens pump function
• Clinical correlate: Resting tachycardia is a sign of sympathetic activation in HF

2. Renin-Angiotensin-Aldosterone System (RAAS):

• Trigger: Reduced renal perfusion + sympathetic activation + hyponatremia
• Pathway: Renin → Angiotensin I → ACE → Angiotensin II (Ang II)
• Ang II effects:
  • Potent vasoconstriction → ↑ afterload
  • Aldosterone release → sodium and water retention → volume overload
  • Promotes cardiac fibrosis, hypertrophy, and remodeling
  • Stimulates further norepinephrine release
• Aldosterone effects:
  • Sodium retention in collecting duct
  • Potassium and magnesium wasting → arrhythmias
  • Promotes myocardial fibrosis and endothelial dysfunction
• Net result: Fluid accumulation → congestion; structural remodeling → progressive dysfunction

3. Arginine Vasopressin (ADH/AVP):

• Released from hypothalamus in response to ↓ CO and elevated plasma osmolarity
• Causes free water retention without sodium → dilutional hyponatremia
• Vasoconstriction → ↑ afterload
• Copeptin is a stable plasma surrogate for vasopressin, elevated in HF

4. Natriuretic Peptides (Compensatory):

• ANP (Atrial Natriuretic Peptide): Released by atrial stretch
• BNP (B-type/Brain Natriuretic Peptide): Released by ventricular wall stress
• NT-proBNP: Inactive N-terminal fragment of pro-BNP
• Actions: Natriuresis, vasodilation, anti-fibrotic, suppresses RAAS
• Limitation: Their compensatory effect is overwhelmed by RAAS/SNS activation in severe HF
• Clinical use: BNP/NT-proBNP are key diagnostic and prognostic biomarkers

5. Endothelin-1:

• Produced by endothelium in response to Ang II, inflammation, vascular shear stress
• Potent vasoconstrictor
• Promotes adverse cardiac remodeling
• Elevated in HF; correlates with severity

6. Inflammatory Cytokines:

• TNF-α, IL-1β, IL-6 are elevated in HF
• Cause progressive myocardial dysfunction
• Contribute to cardiac cachexia and muscle wasting
• Gut congestion → increased intestinal permeability → endotoxemia (LPS) → macrophage activation → cytokine release (gut-heart axis)

7. Galectin-3 and ST2:

• Galectin-3: promotes cardiac fibroblast proliferation and collagen synthesis → maladaptive remodeling; prognostic marker
• sST2 (soluble ST2): secreted from myocytes during biomechanical strain; mediates myocardial hypertrophy and fibrosis; prognostic marker

5c. Ventricular Remodeling:

• Myocyte hypertrophy + interstitial fibrosis (collagen matrix alteration)
• Altered calcium-handling proteins (reduced SERCA2a activity → impaired Ca²⁺ reuptake)
• Re-expression of fetal gene program (β-MHC replaces α-MHC; ANP, BNP re-expressed)
• Myocyte loss via necrosis and apoptosis (programmed cell death)
• Cytoskeletal protein dysfunction
• Afterload mismatch: systemic vasoconstriction + failing ventricle = vicious cycle

5d. HFpEF Pathophysiology:

• Impaired relaxation (lusitropy): reduced Ca²⁺ reuptake into sarcoplasmic reticulum → prolonged diastole
• Increased myocardial passive stiffness from fibrosis and hypertrophy
• Elevated LV filling pressures → pulmonary venous hypertension → dyspnea
• Microvascular inflammation and endothelial dysfunction (driven by comorbidities: obesity, DM, HTN)
• Systemic inflammation → impaired NO signaling → myocardial fibrosis
• Pericardial constraint in obesity contributes to elevated filling pressures

5e. Cardiorenal Syndrome:

• Type 1: Acute worsening of heart → acute kidney injury
• Type 2: Chronic HF → chronic kidney disease
• Mechanisms:
  • ↓ Renal arterial perfusion (forward failure)
  • ↑ Renal venous congestion (backward failure - now recognized as equally important)
  • ↑ Intra-abdominal pressure (right HF)
  • Splanchnic-renal reflex (splenic/hepatic congestion → renal vasoconstriction)
  • Neurohormonal activation (RAAS, SNS, ADH)
• Diuresis relieves both volume AND abdominal pressure → improves renal function

5f. Hemodynamic Summary:

• Preload ↑ (venous return, Na/water retention) → volume overload
• Afterload ↑ (SNS vasoconstriction, RAAS) → impedes ejection
• Contractility ↓ (myocyte loss, remodeling, neurohormonal toxicity)
• Heart rate ↑ (sympathetic activation) - compensatory but ↑ myocardial O₂ demand

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SECTION 6: CLINICAL FEATURES

6a. Symptoms - Left-Sided HF (Pulmonary Congestion):

6b. Symptoms - Right-Sided HF (Systemic Venous Congestion):

6c. Symptoms - Low Cardiac Output:

• Fatigue, lethargy, mental clouding
• Cool, clammy extremities
• Oliguria (advanced HF - severe ↓ renal perfusion)
• Cardiac cachexia: involuntary weight loss >5% in 12 months (edema-free); bitemporal wasting; indicates severe, advanced HF

6d. Physical Signs:

General Appearance:

• Mild-moderate HF: comfortable at rest, distressed with minimal exertion
• Severe HF: sitting upright (cannot lie flat), anxious, diaphoretic, dyspneic at rest
• Pallor (anemia), peripheral cyanosis (low output)
• Cardiac cachexia: bitemporal or upper body muscle wasting

Vital Signs:

Jugular Venous Pressure (JVP):

• Elevated JVP (>4 cm above sternal angle with patient at 45°) = elevated right heart filling pressures
• Hepatojugular reflux (HJR): sustained pressure on RUQ for ≥15 seconds → JVP rises by ≥4 cm → positive = right heart failure
• Kussmaul's sign: JVP rises on inspiration (constrictive pericarditis or severe RVF); normally falls on inspiration

Chest Examination:

• Bilateral basal inspiratory crackles (crepitations): pulmonary edema - small airways snapping open on inspiration
• Stony dullness at bases: pleural effusion (bilateral; more on right)
• Wheeze: "cardiac asthma" (bronchospasm from pulmonary congestion)
• Reduced breath sounds at bases (effusion)

Precordial Examination:

Abdomen:

• Hepatomegaly: tender, firm, smooth; pulsatile in tricuspid regurgitation
• Ascites: advanced right HF; shifting dullness, fluid thrill
• Splenomegaly (sometimes)

Extremities:

• Pitting edema: bilateral, dependent; starts in ankles - progresses to legs, thighs, sacrum, scrotum/labia in bed-bound patients
• Anasarca: generalized edema including ascites and pleural effusions
• Cool extremities with low output
• Peripheral cyanosis (slow flow → ↑ O₂ extraction peripherally)

Signs in Right vs Left HF:

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SECTION 7: PRECIPITATING FACTORS

Clinical pearl: In 25-50% of admissions, no clear precipitant is identified ("unknown/unexplained").

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SECTION 8: INVESTIGATIONS

8a. Routine Blood Tests:

8b. Biomarkers:

Natriuretic Peptides (Most Important):

• BNP rises with: ventricular wall stress, volume overload, ischemia
• BNP may be falsely low in: obesity (adipose tissue clears BNP)
• BNP may be falsely elevated in: AF, PE, renal failure, sepsis, RVF without LVF
• Serial BNP monitoring: falling BNP with treatment = good response; rising BNP = deterioration

Cardiac Troponin (cTnI/cTnT):

• Elevated in HF due to myocyte injury and stretch
• High-sensitivity troponin (hs-cTn) independently predicts mortality in HF
• Rising troponin in CHF patient suggests ACS as precipitant or ongoing myocyte injury

Other Biomarkers (emerging):

• Galectin-3: promotes fibrosis; prognostic marker independent of NPs
• sST2 (soluble ST2): elevated with biomechanical strain; predicts adverse remodeling and poor outcomes
• GDF-15: prognostic marker; potential therapy target
• Cystatin C: more sensitive than creatinine for GFR estimation in HF
• NGAL (Neutrophil Gelatinase-Associated Lipocalin): early marker of renal tubular damage in HF

8c. 12-Lead ECG:

8d. Chest X-Ray (CXR):

CXR correlation with PCWP:

• PCWP 12-18: Upper lobe diversion
• PCWP 18-25: Kerley B lines + perihilar haziness
• PCWP >25: Alveolar edema
• PCWP >30: Pleural effusions

8e. Echocardiography (THE Key Investigation):

Diastolic Dysfunction Grading:

8f. Other Investigations:

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SECTION 9: MANAGEMENT

9a. General Measures (Non-Pharmacological):

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9b. Pharmacological Management of HFrEF - The "FOUR PILLARS" (BAMS):

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PILLAR 1: β-BLOCKERS

• Start LOW, titrate SLOW: double dose every 2 weeks minimum
• Monitor HR, BP, symptoms, signs of congestion, body weight
• Check biochemistry 1-2 weeks after initiation and after final dose titration
• "Some β-blocker is better than no β-blocker"
• Do NOT start in acute decompensated HF (wait until euvolemic)
• Symptomatic improvement may take 3-6 months; initial temporary worsening possible

• Worsening congestion → increase diuretic first, then halve β-blocker dose if still worsening
• HR <50 bpm with symptoms → halve dose; rarely need to stop
• Severe deterioration → halve or stop (rare); seek specialist advice

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PILLAR 2: ARNI (or ACEi or ARB)

• Combines neprilysin inhibitor (sacubitril) + angiotensin receptor blocker (valsartan)
• Neprilysin inhibition → ↑ BNP, ANP → natriuresis, vasodilation, anti-fibrosis
• PARADIGM-HF trial: 20% relative reduction in CV death or HF hospitalization vs enalapril
• Now PREFERRED over ACEi/ARB in symptomatic HFrEF patients who tolerate it
• Starting dose: 24/26 mg BD → target 97/103 mg BD
• IMPORTANT: Cannot combine with ACEi (angioedema risk); must have 36-hour washout from last ACEi dose before starting ARNI

• Block conversion of Ang I → Ang II; also ↑ bradykinin (→ cough, angioedema)
• All-cause mortality reduction; reduce hospitalizations
• Agents: Enalapril, Ramipril, Lisinopril, Captopril, Perindopril
• Start low, titrate to maximum tolerated dose
• Side effects: Dry cough (10-15%; due to ↑ bradykinin - switch to ARB), angioedema (rare, potentially fatal - STOP immediately; do NOT re-challenge), hyperkalaemia, worsening renal function, hypotension
• Contraindications: Bilateral renal artery stenosis, pregnancy (teratogenic - category D), angioedema history, hyperkalemia, severe aortic stenosis

• Block AT1 receptor; do NOT increase bradykinin → no cough
• Agents: Valsartan, Candesartan, Losartan
• Side effects: Hyperkalemia, worsening renal function (less cough/angioedema than ACEi)
• Not superior to ACEi; do NOT combine ACEi + ARB (ONTARGET trial showed no benefit + ↑ harm)

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PILLAR 3: MINERALOCORTICOID RECEPTOR ANTAGONISTS (MRA)

• Block aldosterone → reduce Na retention, cardiac fibrosis, endothelial dysfunction
• RALES trial (spironolactone, EF ≤35%): 30% mortality reduction in severe HF (NYHA III-IV)
• EPHESUS trial (eplerenone, post-MI HF): 15% relative risk reduction in mortality
• Also reduces hospitalizations and improves NYHA class

• Check K⁺ and creatinine at 1, 4, 8, 12 weeks; then 6, 9, 12 months; then 6-monthly
• K⁺ >5.5 mmol/L: reduce to 25 mg alternate days; monitor closely
• K⁺ >6.0 mmol/L or creatinine >310 μmol/L (3.5 mg/dL): STOP immediately

• K⁺ >5.0 mmol/L (significant hyperkalemia)
• Creatinine >221 μmol/L (2.5 mg/dL) or eGFR <30 mL/min
• Concomitant K⁺ supplements or K⁺-sparing diuretics

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PILLAR 4: SGLT-2 INHIBITORS (Sodium-Glucose Cotransporter-2 Inhibitors)

• Osmotic diuresis and natriuresis → ↓ preload
• ↓ Afterload
• Metabolic effects: ketogenesis, fuel substrate shifting
• ↓ Uric acid, ↓ inflammatory markers, ↓ fibrosis

Benefits are independent of diabetes status - proven in non-diabetic HF patients too.

• Now guideline-endorsed as foundational therapy alongside ARNI, β-blocker, and MRA for all HFrEF (and increasingly HFpEF)

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9c. Additional Drug Therapies for HFrEF:

Diuretics (Symptom Relief - No Mortality Benefit):

Ivabradine:

• Pure heart rate reduction (inhibits If "funny current" in SA node); no effect on contractility or BP
• SHIFT trial: significant reduction in HF hospitalizations
• Indication: Sinus rhythm + HR ≥70 bpm despite target β-blocker dose (or β-blocker contraindicated) + symptomatic HFrEF (LVEF ≤35%)
• Starting dose: 5 mg BD → 7.5 mg BD
• Side effect: Visual phosphenes (15%), bradycardia
• Contraindication: AF, bradycardia, sick sinus syndrome

Digoxin (Cardiac Glycoside):

• Mechanism: Inhibits Na⁺/K⁺-ATPase → ↑ intracellular Ca²⁺ → positive inotropy; also slows AV conduction (↓ ventricular rate in AF)
• DIG trial: No mortality benefit; reduces HF hospitalizations in sinus rhythm
• Current indications: HFrEF with persistent symptoms (NYHA II-IV) despite optimal therapy; particularly useful with AF for rate control
• Dose: 0.125-0.25 mg OD (reduce in elderly and CKD)
• Therapeutic level: 0.5-0.9 ng/mL (higher levels not beneficial and increase toxicity)
• Digoxin toxicity:
  • Precipitants: Hypokalemia (most important), hypomagnesemia, renal failure, drugs (amiodarone, verapamil, quinidine all ↑ digoxin levels)
  • Symptoms: Nausea, vomiting, yellow-green xanthopsia (disturbed colour vision), confusion
  • ECG: Reverse tick (scooped ST depression), heart block, VT/VF
  • Treatment: Stop digoxin, correct hypokalemia, digoxin-specific antibody (Fab fragments) for life-threatening toxicity

Hydralazine + Isosorbide Dinitrate (H-ISDN):

• Hydralazine: arterial vasodilator (↓ afterload) + antioxidant
• Isosorbide dinitrate: venous dilator (↓ preload)
• A-HeFT trial: significantly reduced mortality in Black patients with symptomatic HFrEF
• Use: (1) Patients who cannot tolerate ACEi/ARB/ARNI (e.g., bilateral RAS, severe CKD, angioedema); (2) Self-identified Black patients in addition to standard therapy
• Side effects: Headache, palpitations, fluid retention; hydralazine: drug-induced lupus with long-term use

Vericiguat (Soluble Guanylyl Cyclase Stimulator):

• Stimulates sGC → ↑ cyclic GMP → vasodilation
• VICTORIA trial: 10% relative risk reduction in CV death or HF hospitalization in high-risk HFrEF (NYHA II-IV, LVEF <45%, recent hospitalization/IV diuretics despite GDMT)
• Role: Adjunct in high-risk patients with recent decompensation despite GDMT
• Target dose: 10 mg OD

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9d. Approach to Newly Diagnosed HFrEF (Stepwise):

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9e. Device Therapy:

Implantable Cardioverter-Defibrillator (ICD):

• Criteria: LVEF ≤35% + NYHA Class II-III + on optimal GDMT for ≥3 months + life expectancy >1 year
• Do NOT implant within 40 days of MI (DINAMIT trial: no benefit)
• Post-MI with EF ≤30-35% + NYHA I: also qualifies (MADIT-II trial)
• Secondary prevention: Any patient with sustained VT/VF or cardiac arrest (if reversible cause excluded)

• Sudden death in HF is from progressive LV dysfunction, not just focal arrhythmia (except post-MI scar)
• Most benefit at early HF stages; SCD incidence decreases with advancing NYHA class
• ICD discharge ≠ aborted SCD (some arrhythmias self-terminate)
• An appropriate ICD shock is associated with worse near-term prognosis (marker of disease severity)

Cardiac Resynchronization Therapy (CRT):

• LVEF ≤35%
• LBBB with QRS ≥150 ms (QRS 120-149 ms: weaker evidence)
• NYHA Class II-IV despite optimal GDMT
• Sinus rhythm (or AF with controlled HR)

• CRT-P: Pacemaker function only
• CRT-D: Combines CRT + ICD (preferred in eligible patients for both)

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9f. Surgical and Advanced Therapies:

Coronary Artery Bypass Grafting (CABG):

• Indication: Ischemic cardiomyopathy + multivessel CAD ± viable (hibernating) myocardium
• STICH trial: No initial benefit, but long-term 10-year benefit in CV death and all-cause mortality vs medical therapy
• Revascularization most robustly beneficial with ongoing angina + LV dysfunction
• Hibernating myocardium = viable myocardium with abnormal function that may recover after revascularization; assess with PET or cardiac MRI (late gadolinium enhancement)

Mitral Valve Repair/Replacement:

• Functional/secondary MR is common in dilated HFrEF; severity inversely related to prognosis
• Transcatheter edge-to-edge repair (TEER/MitraClip): For severe functional MR in HFrEF patients not amenable to surgery (MITRA-FR and COAPT trials - conflicting results; benefit in patients with disproportionate MR)
• Surgical repair less commonly indicated for functional MR

Left Ventricular Assist Device (LVAD):

• Mechanical pump to assist LV function; implanted surgically
• Indications:
  • Bridge to transplantation (BTT): Stabilize patient while awaiting donor heart
  • Destination therapy (DT): Permanent therapy in transplant-ineligible patients
  • Bridge to recovery: Potentially reversible cardiomyopathies (myocarditis, peripartum)
  • Bridge to decision (while determining transplant eligibility)
• Criteria for LVAD: Stage D HF (INTERMACS profile 1-5), LVEF <25%, VO₂ max <14 mL/kg/min, NYHA IV despite GDMT
• Complications: Stroke, bleeding (especially GI), device infection, pump thrombosis, aortic insufficiency, right HF after LVAD implant

Heart Transplantation:

• Definitive therapy for end-stage HF not responding to other therapies
• 5-year survival: >70%; median survival ~12 years
• Key indication: Stage D HF + VO₂ max <10-12 mL/kg/min (or <14 mL/kg/min with other poor prognostic factors) + no alternative therapy
• Absolute contraindications: Active infection, active malignancy, irreversible pulmonary hypertension (PVR >5 Wood units unresponsive to vasodilators), severe hepatic/renal failure, severe COPD, active substance abuse, poor compliance
• Limited by: Donor organ availability; long waiting lists; lifelong immunosuppression (tacrolimus + mycophenolate ± steroids)
• Post-transplant complications: Rejection (acute cellular, chronic/allograft vasculopathy), infection (opportunistic), malignancy (skin, lymphoma), drug toxicity

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9g. Management of Acute Decompensated HF (ADHF):

Step 1 - Identify Precipitant (Table 46-7):

Step 2 - Clinical Phenotyping ("Wet/Dry + Warm/Cold"):

Step 3 - Volume Management:

• IV Loop Diuretics (furosemide IV 40-200 mg): Essential for acute congestion
  • IV dose should equal or exceed the patient's chronic oral dose
  • Convert to oral when euvolemic
• Thiazide addition (metolazone 2.5-10 mg): For diuretic resistance - "sequential nephron blockade"
• Ultrafiltration: Mechanical fluid removal; for severe diuretic resistance
• Monitor: Daily weight, fluid balance, U&E, creatinine, BP

Step 4 - Vasodilators (Hypertensive/Normotensive ADHF):

• IV nitroglycerin (glyceryl trinitrate): Venodilator + arterial dilator; rapid symptom relief; titrate to BP
• IV nitroprusside: Potent arterial + venous dilation; monitor for cyanide toxicity (limit to 48-72 hours); requires arterial line
• Nesiritide (recombinant BNP): Vasodilation; no mortality benefit; limited use
• Avoid vasodilators in: SBP <90 mmHg, severe aortic stenosis, right HF without LV involvement

Step 5 - Inotropes (Low-Output/Cardiogenic Shock):

Important: Inotropes have no long-term survival benefit and may increase arrhythmia risk. Used as bridge therapy only.

Step 6 - Oxygen Therapy:

• Supplemental O₂ if SpO₂ <90% or PaO₂ <60 mmHg
• High-flow nasal oxygen or Non-invasive ventilation (NIV): CPAP or BiPAP for acute pulmonary edema - reduces intubation rate and improves short-term outcomes
• Invasive mechanical ventilation (intubation): If NIV fails or severe respiratory failure

Step 7 - Monitoring:

• Continuous cardiac monitoring
• Hourly urine output
• BNP/troponin
• Pulmonary artery catheter (Swan-Ganz): Reserved for cardiogenic shock, refractory HF, diagnostic uncertainty - routine use NOT recommended

Predictors of Worse ADHF Outcome:

• BUN >43 mg/dL (15.4 mmol/L)
• SBP <115 mmHg
• Creatinine >2.75 mg/dL (243 μmol/L)
• Elevated troponin + BNP

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9h. Management of HFpEF:

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SECTION 10: COMPLICATIONS

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SECTION 11: PROGNOSIS

Poor Prognostic Indicators:

Temporal Pattern of Death in HF:

• Mild-moderate HF (NYHA II-III): Sudden cardiac death predominates (~50% of deaths)
• Severe HF (NYHA IV): Progressive pump failure predominates (SCD less likely relatively)
• This explains why ICD benefit is greatest in NYHA II-III, not IV

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SECTION 12: EXAM-READY SUMMARY TABLES

Key Drug Doses for HFrEF:

Quick Differentials for Dyspnea + Edema:

• HF, constrictive pericarditis, nephrotic syndrome, hypoalbuminemia (cirrhosis, malnutrition), venous insufficiency, hypothyroidism, drugs (CCBs, glitazones, NSAIDs)

Mnemonics:

• I = No limitation; II = Slight; III = Marked; IV = Rest

• B = β-blocker; A = ARNI; M = MRA; S = SGLT-2i

• P = PE; I = Infection/Ischemia; R = Rhythm disorders; A = Anemia; T = Thyroid; E = Endocarditis/Excess fluid; S = Salt/non-compliance

• A = Alveolar edema (perihilar haze/bat-wing)
• B = Kerley B lines
• C = Cardiomegaly (CTR >0.5)
• D = Dilated pulmonary vessels (upper lobe diversion)
• E = Effusions (pleural)

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