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HEART FAILURE - Complete Exam-Oriented Notes

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PART 1: SYMPTOMS AND SIGNS OF HEART FAILURE

Left Ventricular (LV) Failure

• Dyspnea - the cardinal symptom, occurs in 3 forms:
  • Exertional dyspnea - breathlessness on effort, earliest symptom
  • Orthopnea - breathlessness on lying flat; patient needs extra pillows; due to redistribution of fluid from legs to lungs
  • Paroxysmal Nocturnal Dyspnea (PND) - sudden breathlessness waking the patient from sleep (see below)
• Acute pulmonary edema - severe form of cardiac asthma with frothy sputum
• Cough - often dry, nocturnal
• Fatigue
• Decreased urine output (oliguria due to poor renal perfusion)

• Cardiac: Enlargement of LV, S3 Gallop rhythm, Systolic murmur in apex
• Pulmonary: Crepitations (fine basal crackles), Pleural effusion

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Right Ventricular (RV) Failure

• Leg swelling
• Gastrointestinal symptoms - anorexia (due to hepatic/portal congestion)
• Renal symptoms - oliguria
• Pain in right hypochondrium (due to hepatomegaly)
• Dyspnea

• Raised JVP
• Positive hepatojugular reflux
• Hepatomegaly
• Edema (pitting, bilateral, pretibial)
• Pleural fluid and ascites

Memory Trick - "FACES": Fatigue, Activities limited, Chest congestion, Edema/ankle swelling, Shortness of breath

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Paroxysmal Nocturnal Dyspnea (PND)

• Closely related to nocturnal cough
• Characterized by wheezing (secondary to bronchospasm) = "Cardiac Asthma"
• Most prominent at night
• Acute pulmonary edema is the severe form
• Cheyne-Stokes respiration may also be seen

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Nocturia

• Observed during early heart failure
• Mechanism: Renal perfusion and diuresis are better at night when the patient is supine (fluid redistribution from dependent parts back to circulation)

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Cerebral Symptoms

• Confusion
• Difficulty in concentration
• Impaired memory
• Headache
• Insomnia
• Anxiety

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Nonspecific Symptoms

• Fatigue - low cardiac output + decreased perfusion of skeletal muscles
• Low-grade fever - reduction of cutaneous blood flow
• Anorexia, nausea, abdominal fullness/pain - congestion of liver and portal venous system

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Signs - Detailed

Dependent/Cardiac Edema

• Due to gravity - fluid accumulates over dependent parts
• In ambulant patients: symmetrical in both legs, especially pretibial region and ankles
• Worse in evening, less in morning
• In bedridden patients: sacral region
• Anasarca = generalized edema throughout body in advanced HF; face and upper limbs spared until terminal stages

Cyanosis

• Observed in lips and nail beds
• Extremities appear cold and pale due to reduced blood flow (peripheral cyanosis)

Pulse

• Pulse volume is reduced
• Pulsus alternans = regular alternation between strong and weak pulse = sign of severe heart failure

Blood Pressure

• Reduced pulse pressure - due to reduced stroke volume
• Mild elevation of diastolic BP - due to generalized vasoconstriction
• Hypotension - prominent in acute heart failure

Jugular Venous Pressure (JVP)

• JVP is raised due to elevated systemic venous pressure
• In early HF, JVP may not be raised at rest; demonstrated by:
  • During/immediately after exercise
  • Hepatojugular reflux (sustained pressure on abdomen causing JVP rise) = positive abdominojugular reflux

Third and Fourth Heart Sound

• S3 gallop = highly suggestive of heart failure (pathological third heart sound)
• Triple/quadruple/summation gallop is seen

Respiratory System - Percussion

• Dull percussion notes over the bases of lungs (infrascapular, infra-axillary areas) due to pleural effusion/pulmonary edema

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PART 2: INVESTIGATIONS IN HEART FAILURE

Exam Point: Diagnosis requires evidence of cardiac dysfunction by investigation + identification of underlying cause.

1. Chest X-ray

• Cardiomegaly (CTR >0.5)
• Phantom tumor = fluid in horizontal or oblique fissures of lungs; disappears after diuretics
• Bat's wing appearance = hazy opacification spreading from hilar regions on both sides (associated with pulmonary edema)
• Pleural effusion (bilateral or unilateral)

2. Electrocardiography (ECG)

• Previous MI
• Active ischemia
• Ventricular hypertrophy (e.g., due to hypertension)
• Atrial abnormality
• Arrhythmias and conduction abnormalities

3. Echocardiography (Most Important Investigation)

1. Determine the etiology
2. Detect unsuspected valvular heart disease (e.g., occult mitral stenosis)
3. Identify patients who will benefit from long-term drug therapy (e.g., ACE inhibitors)
4. Assess cardiac chamber dimensions (size and shape), ejection fraction, valvular functions, cardiomyopathies, and regional wall motion abnormalities
5. Differentiate systolic from diastolic heart failure

4. Other Advanced Investigations

• Stress echocardiography - assesses viability in dysfunctional myocardium (stunned/hibernating)
• Nuclear cardiology (Radionuclide angiography - RNA) - quantifies ventricular ejection fraction
• SPECT / PET - assess myocardial viability and ischemia
• Cardiac MRI - assesses delayed enhancement ("infarct imaging"), useful for cardiomyopathies (e.g., amyloid)
• Cardiac catheterization - measures pulmonary artery pressure, left atrial wedge pressure, left ventricular end-diastolic pressure; useful for diagnosis of cardiomyopathies and post-transplant follow-up
• Cardiac biopsy - to assess rejection in transplanted patients
• Cardiopulmonary exercise testing - peak oxygen consumption (VO2) useful in predicting hospital admission and death in severe HF; decides need for defibrillator
• Ambulatory 24-hour ECG (Holter) - for suspected arrhythmia
• Brain Natriuretic Peptide (BNP) / NT-proBNP - marker of risk (>100 pg/mL); highly sensitive for diagnosis; elevated in heart failure, useful to differentiate cardiac from respiratory cause of acute dyspnea
• Blood tests - FBC, liver function, serum urea, creatinine and electrolytes, cardiac enzymes, thyroid function
• Invasive hemodynamic monitoring - selected patients with persistent symptoms despite standard therapies

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PART 3: FRAMINGHAM CRITERIA FOR DIAGNOSIS OF HEART FAILURE (Table 1.85)

Criteria: 1 Major + 2 Minor

Memory for Major: P-D-R-C-A-S-I-P-W or "PND Distended neck veins, Rales, Cardiomegaly, APE, S3, IVP raised, Positive HJR, Weight loss"

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PART 4: COMPLICATIONS IN ADVANCED HEART FAILURE

1. Renal Failure - Cardiorenal Syndrome

• Poor renal perfusion due to low cardiac output
• Worsened by diuretics, ACE inhibitors, ARBs

2. Hypokalemia

• Due to potassium-losing diuretics
• Due to hyperaldosteronism (activation of RAAS)
• Impaired aldosterone metabolism due to hepatic congestion

3. Hyperkalemia

• Due to drugs promoting renal resorption of potassium
• E.g., combination of ACE inhibitors + ARBs + mineralocorticoid receptor antagonists (MRAs)

4. Hyponatremia

• Poor prognostic sign in severe HF
• Due to: diuretics, inappropriate water retention (high ADH secretion), failure of cell membrane ion pump

5. Hepatic Dysfunction

• Due to hepatic venous congestion and poor arterial perfusion

6. Thromboembolism

• DVT and pulmonary embolism due to low cardiac output and immobility
• Systemic emboli in patients with atrial fibrillation or flutter
• Also with intracardiac thrombus (mitral stenosis, MI, LV aneurysm)

7. Atrial and Ventricular Arrhythmias

• AF occurs in 20% of HF patients
• Sudden death in 50% due to ventricular arrhythmia
• Also: ventricular ectopic beats, non-sustained VT
• Causes: electrolyte changes (hypokalemia/hypomagnesemia), underlying heart disease, proarrhythmic effects of sympathetic activation

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PART 5: ARRHYTHMIAS IN HEART FAILURE - PATHOGENESIS

Factors in Pathogenesis of Tachyarrhythmias

Key Exam Points on Arrhythmias:

• Most common SVA in HF = Atrial Fibrillation (AF)
• AF and congestive HF exacerbate each other
• Ventricular rate control is paramount in tachycardia-related cardiomyopathy
• Patients with HFpEF are dependent on adequate ventricular filling - onset of AF causes rapid HF

• 80% of HFrEF patients have frequent and complex ventricular arrhythmias

• ~50% have non-sustained VT
• Sustained VT and VF = main mechanisms of sudden cardiac death in HF

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PART 6: STAGES OF HEART FAILURE (ACC/AHA Classification)

Key point: Disease progression is unidirectional - from A→B→C→D. The goal of treatment is to prevent progression.

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PART 7: MANAGEMENT OF HEART FAILURE

Aims of Treatment (4 Goals):

1. Relief of symptoms
2. Prevention and control of disease causing cardiac dysfunction
3. Arrest disease progression
4. Improve quality and length of life

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A. General/Lifestyle Measures

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B. Drug Therapy

Principle: Heart function improved by (1) increasing contractility, (2) reducing preload, (3) reducing afterload

1. Diuretics

• In severe HF: combination of loop + thiazide may be needed
• Regular monitoring of serum electrolytes and renal function (risk of hypokalemia and hypomagnesemia)
• Spironolactone (MRA) = potassium-sparing diuretic; beneficial in HF with severe LV systolic dysfunction

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2. Angiotensin Receptor-Neprilysin Inhibitor (ARNI): Sacubitril-Valsartan

• Sacubitril inhibits neprilysin (neutral endopeptidase) → increased natriuretic peptides → vasodilation and natriuresis
• Valsartan = direct antagonism of AT2 receptors (ARB component)

• Allow 36-hour washout period when switching from ACE inhibitors (risk of angioedema)
• Use in stable patients with SBP >100 mmHg
• No recent IV vasodilator or inotrope
• K+ <5 mEq/L
• Monitor volume status

• Start: Sacubitril 24 mg / Valsartan 26 mg twice daily
• Double every 1-2 weeks
• Target: 97/103 mg twice daily

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QUICK REVISION TABLE - Exam High-Yield Points

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HEART FAILURE - Drug Therapy & Advanced Management (Complete Exam Notes)

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PART 1: PHARMACOLOGICAL MANAGEMENT - DRUG-BY-DRUG

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1. ACE INHIBITORS (ACEI)

Mechanism of Action

• Peripheral vasoconstriction
• Activation of the sympathetic nervous system
• Salt and water retention due to aldosterone release

Uses

• Improve survival in all functional classes (NYHA I-IV)
• Given to ALL patients at risk of developing HF
• Improve effort tolerance and mortality
• Prevent onset of overt HF in patients with asymptomatic HF following myocardial infarction

Initiation

• Start at low dose
• Gradually increase over few days to weeks to target/maximum tolerable dose
• Regular blood pressure monitoring required
• Measure serum creatinine concomitantly
• Stop potassium-sparing diuretics before starting

Drugs and Doses (EXAM IMPORTANT - memorize these)

Mnemonic for ACEi in HF: CELR - Captopril, Enalapril, Lisinopril, Ramipril

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2. ANGIOTENSIN II RECEPTOR ANTAGONISTS (ARA/ARBs)

Indications

• Second-line therapy in patients intolerant of ACEI (e.g., due to cough) or as alternative to ACEI

Drugs and Doses

• Same initiation and monitoring protocol as ACEI
• Titration done by doubling the dose

Key Point: Do NOT combine ACEI + ARB + MRA (triple blockade) - increases risk of hyperkalemia and renal failure

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3. BETA-ADRENOCEPTOR BLOCKERS (Beta-Blockers)

Indications

• All patients with current or prior HF and LVEF ≤40% (HFrEF) in the absence of a contraindication

How to Start

• Start low dose, increase gradually over 12 weeks
• Can be started even during hospitalization (not in acute decompensation)

Drugs and Doses

Mnemonic: BCM - Bisoprolol, Carvedilol, Metoprolol succinate

Exam Note: Carvedilol is a non-selective beta-blocker with alpha-1 blocking activity. Bisoprolol and metoprolol succinate are cardioselective (beta-1 selective). Only these 3 are proven to reduce mortality in HF.

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4. SGLT2 INHIBITORS (Newest Addition - Very High Exam Importance)

Drugs

• Dapagliflozin (DAPA-HF trial)
• Empagliflozin (EMPEROR-Reduced trial)

Mechanisms of Action (Multiple mechanisms - know all)

1. Osmotic diuresis and natriuresis → reduce preload → lower congestion and cardiac filling pressures
2. Enhance myocardial utilization of ketones → improve cardiac metabolism → increase cardiac efficiency and reduce myocardial oxygen consumption
3. Improve endothelial function
4. Decrease arterial stiffness
5. Mitigate cardiac fibrosis and inflammation → enhance cardiac remodeling

Clinical Benefits (from major trials)

• Reduce heart failure hospitalization
• Reduce cardiovascular mortality
• Reduce progression of kidney disease

Exam Tip: SGLT2 inhibitors are now part of the "four pillars" of HFrEF therapy alongside ACEI/ARNI, beta-blockers, and MRA.

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5. ALDOSTERONE RECEPTOR ANTAGONISTS (MRA - Mineralocorticoid Receptor Antagonists)

Indications

• NYHA Class II-IV
• EF <35%
• No contraindication:
  • GFR >30 mL/min
  • Creatinine: <2.5 mg/dL (male), <2.0 mg/dL (female)
  • K+ <5 mEq/L
• Improve survival in HF

Drug and Dose

• Spironolactone: 12.5-25 mg once daily, titrated to 50 mg daily

Monitoring Protocol (EXAM - very specific)

• Stop all potassium supplements before starting
• Check K+ and creatinine:
  • 2-3 days after starting
  • Then at 1 week
  • Then monthly for 3 months
  • Then every 3 months
  • And when clinically indicated

Side Effects

• Hyperkalemia (10-15%)
• Gynecomastia or breast pain (anti-androgen effect - specific to spironolactone; use eplerenone to avoid this)

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6. DIGOXIN (Cardiac Glycoside)

Uses

• Patients with atrial fibrillation with heart failure (primary indication)
• Add-on therapy in symptomatic HF patients already on ACEI and beta-blockers
• No mortality benefit - only decreases frequency of hospitalizations

Dosing

• No loading dose required in HF
• Usual dose: 0.125-0.25 mg daily
• Low dose 0.125 mg on alternate days if:
  • Age >70 years
  • Chronic kidney disease
  • Low lean body mass
• Maintain plasma concentration: 0.5-0.9 ng/dL (narrow therapeutic range - easily toxic)

Exam Tip: Digoxin toxicity is enhanced by hypokalemia. Signs: nausea, vomiting, visual disturbances (yellow-green halos), arrhythmias. Digoxin toxicity treated with digoxin-specific antibody fragments (Digibind).

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7. VASODILATORS AND NITRATES (Hydralazine-Nitrate Combination)

• Combination of hydralazine (reduces afterload) + nitrates (reduce preload)
• Use is limited by:
  • Pharmacological tolerance
  • Hypotension
• Used when ACEI/ARB/ARNI are not tolerated (e.g., renal failure, hyperkalemia)

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PART 2: NON-PHARMACOLOGICAL (DEVICE) TREATMENT

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A. Implantable Cardioverter Defibrillator (ICD)

Indication (EXAM IMPORTANT - very specific criteria)

• Nonischemic OR ischemic heart disease (at least 40 days post-MI)
• LVEF <35% with NYHA Class II or III symptoms
• OR NYHA I with EF <30%
• On chronic medical therapy
• Reasonable expectation of meaningful survival >1 year

Rationale

• Patients with symptomatic ventricular arrhythmias + HF have a very bad prognosis
• ICD improves survival irrespective of their response to antiarrhythmic drug therapy

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B. Cardiac Resynchronization Therapy (CRT)

Indication (EXAM - memorize all 4 criteria)

1. LVEF ≤35%
2. Sinus rhythm
3. Left bundle branch block (LBBB) with QRS duration ≥150 ms
4. NYHA Class II, III, or ambulatory IV symptoms

Mechanism

• Both LV and RV are paced simultaneously
• Generates a more coordinated left ventricular contraction
• Improves cardiac output
• Improves symptoms AND survival

Exam Note: CRT-D = CRT + ICD combined device. This is preferred in patients who meet criteria for both.

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C. Coronary Revascularization

• Coronary artery disease = most common cause of HF
• Patients with angina + LV dysfunction: higher mortality from surgery (10-20%), but symptoms and prognosis are improved
• CABG or PCI may improve function in "hibernating" myocardium
• Hibernating myocardium identified by:
  • Stress echocardiography
  • Specialized nuclear imaging
  • MR imaging
• Before recommending surgery: consider age, symptoms, and evidence of reversible myocardial ischemia

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D. Hibernating Myocardium vs Myocardial Stunning (FREQUENTLY EXAMINED - Know the difference)

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E. Cardiac Transplantation

Indication

• Younger patients with severe intractable HF
• Life expectancy <6 months despite optimal therapy
• Most common indications: coronary artery disease and dilated cardiomyopathy

Contraindications

• Pulmonary vascular disease due to long-standing left HF
• Complex congenital heart disease (e.g., Eisenmenger's syndrome)
• Primary pulmonary hypertension

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F. Ventricular Assist Devices (VADs)

1. Bridge to cardiac transplantation (most common use)
2. Potential long-term therapy (destination therapy)
3. Short-term restoration therapy after a potentially reversible insult (e.g., viral myocarditis)

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PART 3: NEWER AGENTS IN HEART FAILURE MANAGEMENT

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1. Nesiritide (Recombinant analog of BNP)

Actions

1. Increase natriuresis, diuresis, and cardiac index
2. Reduce pulmonary capillary wedge pressure (PCWP), pulmonary artery pressure, pulmonary vascular resistance, and systemic blood pressure (dose-dependent)
3. Reversal of deleterious neurohormonal response in HF
4. Reduce levels of endothelin-1, aldosterone, and norepinephrine

Advantages

• Does NOT require ICU admission or invasive monitoring
• Lower incidence of tachycardia and proarrhythmic effects
• Reduces need for supportive therapies like diuretics

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2. Endopeptidase Inhibitor

• ACE + neutral peptidases inhibitor
• Example: Omapatrilat

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3. Levosimendan (Calcium Sensitizer)

• Novel agent with inotropic properties
• Developed specifically for ADHF (Acute Decompensated Heart Failure)
• Mechanism: Acts by sensitizing Troponin C to calcium → increases myocardial contractility without increasing oxygen demand
• Advantage over traditional inotropes: does not cause arrhythmias through calcium overload

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4. Endothelin Receptor Antagonists

• Examples: Bosentan, Tezosentan
• Effective in: acute coronary syndromes, acute renal failure, acute HF
• Indirectly improve contractility
• Decrease pulmonary capillary wedge pressure

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5. Vasopressin Antagonists (V2RA)

• Examples: Tolvaptan, Lixivaptan, Conivaptan
• Used as adjuvant to diuretics in advanced HF
• Mechanism: Block ADH (vasopressin) receptors → free water excretion (aquaresis) without sodium loss
• Useful in hyponatremia in HF

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6. Other Newer Agents

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PART 4: MANAGEMENT BASED ON HEMODYNAMIC PROFILE (Fig. 1.48)

• Cardiac output (vertical axis - perfusion: warm vs. cold)
• Pulmonary capillary wedge pressure (horizontal axis - congestion: dry vs. wet)

Exam Tip: "Cold" = low perfusion = low cardiac output. "Wet" = congested = high PCWP. The worst scenario is "Cold and Wet" - these patients need the most aggressive therapy.

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PART 5: ACC/AHA STAGES - TREATMENT PYRAMID (Fig. 1.49)

Stage A - Asymptomatic, No Heart Damage, High-Risk Factors

• Risk factor control (hypertension, diabetes, obesity, smoking)
• Lipid management
• Treat atrial fibrillation
• Patient and family education
• ACE inhibitors and ARAs in some patients

Stage B - Asymptomatic but Have Signs of Structural Heart Damage

• All Stage A measures
• ACE inhibitors and ARBs in some patients
• Control BP, diabetes; weight reduction; quit smoking; lipid management

Stage C - Symptomatic HF (Current or Previous Symptoms) + Structural Heart Damage

• All Stage A + B measures
• ACE inhibitors or ARBs in all patients
• Beta-blockers in selected patients
• Spironolactone (if LVEF <40%)
• Dietary restriction of sodium, diuretics, and digoxin
• Device therapy: CRT (if bundle branch block), ICD
• Depending on cause: revascularization, mitral valve surgery
• Aldosterone receptor antagonists
• Surgical consultation for coronary artery revascularization and valve repair/replacement

2022 ACC/AHA/HFSA Update: ARNI (sacubitril-valsartan) preferred over ACEi in NYHA Class II-III. ACEi or ARB in Class II-IV.

Stage D - End-Stage Disease, Refractory Symptoms Requiring Special Intervention

• All Stage A, B, C measures
• Temporary intravenous inotropic support
• Mechanical circulatory support depending on cause:
  • Intra-aortic balloon pump (IABP)
  • Ventricular assist devices (VADs)
  • Device therapy - permanent implantable VAD
  • Cardiac transplantation / artificial heart

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PART 6: REFRACTORY HEART FAILURE

• Marked HF symptoms interfering with daily life + recurrent hospitalizations despite optimizing GDMT
• = Stage D as per ACC/AHA guidelines
• Managed as end-stage HF - novel agents and non-pharmacological agents can be tried
• See Stage D treatment above

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PART 7: BRAIN NATRIURETIC PEPTIDE (BNP) - Short Essay Format

Discovery and Structure

• Named "brain" natriuretic peptide because first discovered in porcine brain
• Actually predominantly secreted by ventricles (not the brain in humans)
• A 32-amino acid peptide secreted in response to:
  • Left ventricular stretching
  • Increased wall tension
• Secreted along with an inactive 76-amino acid N-terminal fragment = NT-proBNP

Activation

• Activated after a prolonged period of volume overload
• Similar action to ANP (atrial natriuretic peptide) but greater diagnostic and prognostic value
• Reason: longer half-life than ANP

Normal Values

• BNP < 50 pg/mL (or <50 ng/L) = normal

Diagnostic and Prognostic Utility

• BNP levels are raised in conditions with LV systolic dysfunction
• Used for:
  1. Diagnosis of congestive HF
  2. Useful in emergency room when clinical diagnosis is uncertain
  3. Assess prognosis in HF
  4. Monitor response to therapy in HF
  5. Raised BNP = increased risk of death or cardiovascular events

Other Conditions with Raised BNP (EXAM - "false positives")

• Renal failure (decreased clearance)
• Pulmonary embolism
• Pulmonary hypertension
• Chronic hypoxia
• Atrial fibrillation
• Acute myocardial infarction
• Obese patients
• Sepsis

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QUICK REVISION TABLES

Drug Doses - High-Yield Summary

Device Therapy - Criteria Comparison

Classic Exam One-Liners