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Antiarrhythmic Drugs - Complete Study Guide

The Cardiac Action Potential (Foundation)

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Vaughan-Williams Classification

Class I - Sodium Channel Blockers

Class IA - Intermediate dissociation, PROLONGS APD & QT

• Quinidine: Cinchonism (tinnitus, headache, visual disturbances), hemolytic anemia, torsades de pointes, thrombocytopenia
• Procainamide: Drug-induced lupus-like syndrome (reversible), hypotension; active metabolite NAPA (N-acetylprocainamide) can cause torsades in renal failure patients
• Disopyramide: Significant antimuscarinic effects (urinary retention, dry mouth); can precipitate heart failure

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Class IB - Fast dissociation, SHORTENS APD

• Lidocaine: IV only (extensive first-pass if oral). Neurologic toxicity - tremor, paresthesias, confusion, seizures
• Mexiletine: Oral lidocaine analogue; GI side effects (nausea, dyspepsia)

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Class IC - Slow dissociation, NO CHANGE in APD

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Class II - Beta-Blockers

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Class III - Potassium Channel Blockers (prolong repolarization)

Amiodarone (the "dirty drug" - most important for exams)

• Pulmonary toxicity - pneumonitis, fibrosis (most serious)
• Hepatotoxicity - transaminase elevation, cirrhosis
• Thyroid dysfunction - both hypo- and hyperthyroidism (contains iodine; structurally like T4)
• Corneal microdeposits - reversible; optic neuritis (rare)
• Blue-gray skin discoloration (sun-exposed areas)
• Peripheral neuropathy
• Many drug interactions via CYP inhibition (raises levels of warfarin, digoxin, statins)

Other Class III drugs

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Class IV - Calcium Channel Blockers

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"Other" Antiarrhythmic Drugs

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Drug-to-Arrhythmia Matching (Exam Favorite)

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QT-Prolonging Drugs (High-Yield for Exams)

• Class IA: Quinidine > procainamide, disopyramide
• Class III: Sotalol, dofetilide, ibutilide (amiodarone - low risk despite QT prolongation)

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Quick Mnemonics

• Class IA: "Quinidine Promotes Depolarization" (Quinidine, Procainamide, Disopyramide)
• Amiodarone toxicity: "PLATE" - Pulmonary, Liver, Athyroid, Thyroid, Eye (corneal)
• Adenosine reversal: Caffeine and theophylline are xanthines that block adenosine receptors - they antagonize its effect
• Class IC + MI = Bad: CAST trial - flecainide/encainide increased mortality post-MI despite suppressing PVCs

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Congestive Heart Failure - Complete Study Guide

Definition

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Classification

By Ejection Fraction (Modern, Most Important)

ACC/AHA Staging (A-D) - "Cannot go backward"

NYHA Functional Classification (Symptom severity)

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Causes / Etiology

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Pathophysiology

Two Harmful Neurohormonal Cascades:

• Low CO → renin → Angiotensin I → ACE → Angiotensin II
• AII → vasoconstriction, myocyte hypertrophy, apoptosis, ventricular fibrosis
• AII → aldosterone → Na⁺/water retention → increased preload → worsens congestion

• Low CO → ↑ norepinephrine → tachycardia, vasoconstriction
• Catecholamines → direct myocardial toxicity (Ca²⁺ overload), LVH, arrhythmias, ↑ O₂ demand
• Chronic: downregulation of β-adrenergic receptors

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Clinical Features

Symptoms

Signs

• JVD (most reliable sign of elevated venous pressure)
• S3 gallop (pathological, sign of volume overload / dilated LV)
• S4 gallop (stiff, non-compliant LV - diastolic dysfunction)
• Displaced, sustained apical impulse
• Bilateral basal crackles (pulmonary edema)
• Cheyne-Stokes breathing (severe HF)
• Cool peripheries (low CO)

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Investigations

• Alveolar edema ("bat wing" opacities)
• B-lines (Kerley B lines - interstitial edema)
• Cardiomegaly (CTR > 0.5)
• Distended upper lobe veins (vascular redistribution)
• Effusions (pleural)

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Pharmacological Management

HFrEF - Evidence-Based Drug Therapy (MORTALITY-REDUCING DRUGS)

1. ACE Inhibitors / ARBs (RAAS Blockade)

2. Beta-Blockers

• Block harmful effects of catecholamines, reverse remodeling, reduce sudden cardiac death
• Start low, go slow - never start during acute decompensation
• Reduce resting heart rate to 55-60 bpm target
• Carvedilol also has alpha-1 blocking (vasodilatory) properties

3. Mineralocorticoid Receptor Antagonists (MRAs)

• Block aldosterone escape, reduce cardiac fibrosis
• Watch for: Hyperkalemia, gynecomastia (spironolactone)
• Use if K⁺ < 5.0 mmol/L and GFR > 30

4. SGLT2 Inhibitors (newest pillar - now standard of care)

• Reduce HF hospitalizations and cardiovascular death regardless of diabetes status
• Mechanism in HF: osmotic diuresis, reduced preload/afterload, improved cardiac metabolism
• Also benefit HFpEF (EMPEROR-Preserved, DELIVER trials)

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Additional Drugs

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HFpEF Management

• Treat underlying cause (HTN, AFib, volume overload)
• Diuretics for congestion symptoms
• SGLT2 inhibitors (dapagliflozin, empagliflozin) - now shown to reduce hospitalizations
• BP control (target < 130/80 mmHg)
• Rate control for AFib (non-dihydropyridine CCBs are safe here, unlike HFrEF)

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Drugs to AVOID in HFrEF

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Device Therapy (Non-Pharmacologic)

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Quick Summary: Drug Targets in HF

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Key Exam High-Yield Points

• BNP is the best biomarker for HF diagnosis and monitoring
• Echocardiogram is the investigation of choice
• S3 gallop = volume overload (HFrEF); S4 gallop = stiff LV (HFpEF)
• Sacubitril/valsartan is now preferred over ACE inhibitors in stable HFrEF (PARADIGM-HF)
• SGLT2 inhibitors are the newest pillar - benefit in both HFrEF and HFpEF
• Beta-blockers reduce sudden cardiac death (↓ mortality from arrhythmia)
• Spironolactone - monitor K⁺; contraindicated if K⁺ > 5.0 or GFR < 30
• Carvedilol is preferred over non-selective beta-blockers (also blocks alpha-1)
• Only amiodarone and dofetilide are safe antiarrhythmics in HF
• ACC/AHA stages cannot go backward (unlike NYHA which can improve with treatment)

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Acute Heart Failure - Complete Study Guide

Definition

• New-onset AHF - first presentation (e.g., large MI, acute valvular rupture)
• Acute-on-chronic HF - decompensation of previously stable chronic HF (most common)

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Pathophysiology

What happens immediately after acute cardiac damage

Neurohormonal cascade (from Guyton & Hall)

1. Cardiac output falls → baroreceptors fire → sympathetic nervous system activated
2. Norepinephrine released → tachycardia, vasoconstriction, increased venous return (↑ preload)
3. Renal perfusion falls → RAAS activated → angiotensin II + aldosterone → Na⁺/water retention
4. Vasopressin (ADH) released → water retention
5. Endothelin-1 → potent vasoconstriction
6. TNF-α, cytokines → endothelial dysfunction
7. Net result: ↑ filling pressures → pulmonary and peripheral congestion

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Clinical Classification of AHF (6 Phenotypes - Tintinalli)

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Common Precipitants of Acute Decompensation

• P - Pulmonary embolism
• I - Infection (pneumonia, sepsis)
• R - Rhythm disorder (new AFib most common)
• A - Anemia / Acute MI
• T - Treatment non-compliance (salt, fluids, medications)
• E - Endocrine (thyrotoxicosis)
• S - Substance abuse (alcohol, cocaine) / Salt excess

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Clinical Features

Symptoms

Signs

• Tachycardia, tachypnea
• JVD (elevated venous pressure)
• Bilateral basal crackles (pulmonary edema)
• S3 gallop (volume overload)
• Peripheral pitting edema
• Displaced/sustained apex beat
• Hepatomegaly, hepatojugular reflux

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Investigations

• BNP < 100 pg/mL: HF unlikely
• BNP > 400 pg/mL: HF likely
• Grey zone 100-400: consider other causes (PE, COPD, renal failure also raise BNP)

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Emergency Management

Immediate Priorities (ABC approach)

1. Airway/Breathing - oxygen to maintain SpO₂ ≥ 95%
2. Sit patient upright - reduces preload
3. IV access + monitoring - ECG, SpO₂, urine output
4. Identify and treat precipitant

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Treatment by Phenotype

A. Hypertensive AHF / Pulmonary Edema

• Key point: In hypertensive AHF, fluid redistribution (not overload) is the main problem - symptoms may resolve with vasodilators alone without needing large doses of diuretics
• NTG complication: hypotension (give 250-1000 mL NS if persistent)

• IV preferred over oral in acute setting (bowel wall edema reduces oral absorption)
• Onset of diuresis: ~10-15 minutes IV
• Monitor: K⁺, Cr, urine output (target 0.5-1 mL/kg/hr)
• If inadequate response: double dose and repeat in 30-60 min; consider adding acetazolamide

• CPAP or BiPAP if severe dyspnea or hypoxia despite O₂
• Reduces work of breathing and need for intubation
• Indicated: SpO₂ < 90% despite O₂, RR > 25, PaCO₂ rising

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B. Normotensive AHF (Acute-on-Chronic)

• Loop diuretics first
• Titrate based on urine output and symptoms
• Add vasodilator if congestion persists despite diuretics
• Continue chronic HF medications if tolerated

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C. Cardiogenic Shock (SBP < 90 mmHg)

• Inotropes reserved for: hypotension, end-organ dysfunction, unresponsive to standard therapy
• Consider IABP (intra-aortic balloon pump) or ECMO in refractory cardiogenic shock
• Urgent revascularization if ACS-related (PCI/CABG)

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D. High-Output Heart Failure

• Treat the underlying cause (transfuse for anemia, antithyroid drugs for thyrotoxicosis, thiamine for beriberi)
• Diuretics if congested, but avoid excessive volume removal

E. Right Heart Failure

• Identify cause (PE? Pulmonary HTN? RV infarct? Valvular?)
• Avoid aggressive diuresis - RV is preload dependent
• Treat underlying cause
• Optimize right ventricular preload carefully

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Medications Table Summary

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Disposition / Admission Criteria

• Altered mental status
• Persistent hypoxia despite NIV
• Hypotension
• Troponin elevation / ischemic ECG changes
• Tachycardia / tachypnea not responding
• Inadequate urine output

• Good response to therapy
• No high-risk features
• Good social support and follow-up

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AHF in the Context of Acute MI

• Priority: Rapid coronary reperfusion (PCI or thrombolysis)
• IV furosemide acutely reduces LVEDP in 5-15 minutes via venodilation (before diuresis begins)
• Use diuretics judiciously - avoid reducing preload too aggressively (may reduce CO further)
• Vasodilators (isosorbide dinitrate) + furosemide = best first-line combination in LVF complicating MI
• Inotropes if cardiogenic shock develops

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Key Exam Points

• Vasodilators before diuretics in hypertensive AHF (fluid redistribution, not just overload)
• Diuretics first in normotensive acute-on-chronic HF with edema
• CPAP/BiPAP reduces intubation need in pulmonary edema
• Dobutamine = inotrope of choice for cardiogenic shock with near-normal BP
• Avoid morphine in AHF - associated with worse outcomes in recent data
• BNP is the best biomarker; also used to monitor response to treatment
• Torsemide may have advantages over furosemide (better bioavailability, less re-admissions)
• Diuretic resistance: try higher IV dose, add thiazide (metolazone), or consider ultrafiltration
• In AHF + hyponatremia: vasopressin antagonists (tolvaptan, conivaptan) may help symptoms but do NOT reduce mortality
• Nesiritide reduces PCWP but does NOT improve mortality vs. standard therapy

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