Cardiovascular Pharmacology: Heart Failure and Arrhythmias (CV4, CV5, CV6)

Comprehensive vocabulary flashcards covering the entire cardiovascular pharmacology sequence for heart failure (CV4), arrhythmia fundamentals/atrial fibrillation (CV5), and advanced arrhythmias/ventricular tachycardia (CV6).

Heart Failure with Reduced Ejection Fraction (HFrEF)

A clinical diagnosis characterized by ventricular dilation, diminished contractility, and an ejection fraction below normal, leading to reduced cardiac output and tissue perfusion.

Ejection Fraction (EF)

The fraction of blood pumped out of the left ventricle relative to the total volume filled prior to each heartbeat.

Normal Ejection Fraction

An ejection fraction of at least $50\%$ under healthy physiological conditions.

Cardiac Output (CO)

The total volume of blood pumped by the heart per unit of time, calculated as the product of stroke volume and heart rate.

Left Ventricular (LV) Dilation

Structural remodeling in which the left ventricular cavity enlarges while the muscular chamber walls become thinner and mechanically compromised.

Exertional Dyspnea

Shortness of breath brought on by physical exertion, presenting as a hallmark clinical manifestation of heart failure in Sarah.

Ankle Edema

Peripheral fluid accumulation in the lower extremities secondary to venous congestion and enhanced sodium and water retention.

Blood Pressure Relationship ($BP = CO \times TPR$)

The hemodynamic equation demonstrating that blood pressure depends directly on cardiac output and total peripheral resistance.

Total Peripheral Resistance (TPR)

The vascular resistance against which blood flows throughout the systemic circulation, which elevates compensatory vasoconstriction.

Carotid Sinus Stretch in Low CO

A reduction in arterial wall stretch within the carotid arteries triggered by low blood pressure, driving neurohormonal compensatory activation.

Neurohormonal Response in Heart Failure

The compensatory physiological activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system in response to low systemic perfusion.

Sympathetic Nervous System (SNS) Compensatory Role

Initial physiological release of norepinephrine to raise heart rate, contractile force, and peripheral vascular tone to restore blood pressure.

Chronic Norepinephrine Toxicity

Prolonged adrenergic signaling resulting in direct cardiomyocyte damage, adverse cardiac remodeling, and heightened arrhythmia risk.

Renin-Angiotensin-Aldosterone System (RAAS) Activation

Enzymatic cascade triggered by decreased renal perfusion and sympathetic tone that promotes vasoconstriction and fluid retention.

Angiotensin II

A potent peptide that directly induces arterial vasoconstriction, raises afterload, stimulates aldosterone release, and increases myocardial fibrosis.

Afterload

The systemic arterial resistance that the left ventricle must overcome to eject blood, where high levels impair cardiac output further.

Aldosterone

A mineralocorticoid hormone promoting renal sodium and fluid reabsorption, expanding circulating plasma volume and increasing preload.

Preload

The end-diastolic volume filling and stretching the ventricular muscle; excessive expansion exacerbates congestion in a failing heart.

Congestion in Heart Failure

Venous fluid backup into the pulmonary bed and dependent peripheral tissues occurring when the failing ventricle cannot efficiently pump forward.

Beta-Blocker Paradox in HFrEF

The therapeutic rationale of administering a negative inotrope like Metoprolol to block long-term detrimental adrenergic remodeling despite low baseline CO.

Metoprolol Titration Strategy

Starting the drug at a very low dosage and gradually titrating upward in clinical trials to ensure therapeutic protection outweighs inotropic depression.

Metoprolol Formulation Switching

Adjusting a patient from a rapid-release formulation to an extended-release preparation to maintain continuous adrenergic blockade.

ARNI (Angiotensin Receptor-Neprilysin Inhibitor)

A dual-action pharmacological class combining an ARB and an enzyme inhibitor, exemplified by Sacubitril + Valsartan.

Sacubitril

A neprilysin inhibitor that prevents the enzymatic breakdown of beneficial endogenous natriuretic peptides.

Neprilysin

The metalloprotease enzyme responsible for clearing and degrading ANP and BNP into biologically inactive metabolites.

Atrial Natriuretic Peptide (ANP) and Brain Natriuretic Peptide (BNP)

Cardiac peptides that promote systemic vasodilation to reduce afterload and induce urinary sodium/water excretion to decrease preload.

Valsartan

An angiotensin receptor blocker (ARB) that prevents Angiotensin II-mediated vasoconstriction, reducing systemic resistance and afterload.

Mineralocorticoid Receptor Antagonist (MRA)

A drug class that blocks aldosterone receptors in the renal collecting duct, reducing preload without sacrificing potassium.

Spironolactone

An MRA that downregulates ENaC in the renal collecting duct, promoting sodium and water excretion to lower preload.

ENaC (Epithelial Sodium Channel)

The apical collecting duct channel through which aldosterone drives sodium reabsorption, targeted indirectly by Spironolactone.

Spironolactone-Induced Gynecomastia

Breast enlargement in males caused by Spironolactone's non-selective binding and inhibition of androgen/testosterone receptors.

Eplerenone

A selective mineralocorticoid receptor antagonist alternative that does not bind testosterone receptors, avoiding gynecomastia.

SGLT2 (Sodium-Glucose Cotransporter 2)

A renal transporter located in the early proximal tubule responsible for reabsorbing filtered glucose along with sodium back into blood.

Dapagliflozin

An SGLT2 inhibitor originally introduced for diabetes that blocks renal glucose and sodium reabsorption, promoting osmotic diuresis.

Osmotic Diuresis by Dapagliflozin

The excretion of urinary glucose and sodium that draws free water along with them, reducing circulating volume and cardiac preload.

Dr. Peter Light's Lab

The University of Alberta research group referenced for uncovering novel cardioprotective mechanisms of SGLT2 inhibitors.

Furosemide

A loop diuretic reserved for significant congestive symptoms to elicit rapid and substantial diuresis.

NKCC2 ($Na^+-K^+-2Cl^-$ Cotransporter)

The major transport protein in the thick ascending limb of the loop of Henle responsible for extensive sodium reabsorption, inhibited by Furosemide.

Amlodipine Discontinuation in Sarah

The clinical withdrawal of a DHP calcium channel blocker due to potential exacerbation of peripheral ankle edema in heart failure.

Losartan Discontinuation in Sarah

The clinical replacement of single-agent Losartan in Sarah's regimen with the superior combination therapy Sacubitril + Valsartan.

Sarah's Comprehensive HFrEF Regimen

The combined pharmacotherapy consisting of Sacubitril + Valsartan, Spironolactone, Metoprolol, Dapagliflozin, Atorvastatin, and Aspirin.

Sinoatrial (SA) Node

The primary intrinsic pacemaker of the heart that spontaneously initiates electrical impulses to coordinate rhythmic contractions.

Cardiac Conduction System Pathway

The sequential electrical route comprising SA node, atrial myocardium, AV node, Bundle of His, bundle branches, and Purkinje network.

Autonomic Independence of Cardiac Pacemakers

The ability of the heart to continue rhythmic spontaneous beating even after all autonomic innervation is severed, as in cardiac transplantation.

Nodal Action Potential

The slow-response electrical waveform characteristic of SA and AV nodal cells, consisting of Phase 0, Phase 3, and Phase 4.

Phase 0 in AV Nodal Cells

The upstroke depolarization phase driven predominantly by the inward influx of calcium through L-type $Ca^{2+}$ channels.

Phase 3 in AV Nodal Cells

The repolarization phase mediated by outward potassium flux through $K^+$ channels, restoring negative intracellular potential.

Phase 4 Pacemaker Potential

The slow, spontaneous diastolic depolarization seen in nodal cells that gradually raises membrane potential toward the excitation threshold.

Non-Contractile Nature of Nodal Cells

The cellular characteristic where pacemaker and nodal cells generate and conduct impulses without undergoing excitation-contraction coupling.

Cardiomyocyte Action Potential

The fast-response electrical waveform characteristic of atrial and ventricular contractile myocytes, featuring five distinct phases (0 through 4).

Phase 0 in Cardiomyocytes

Rapid membrane depolarization caused by the opening of fast voltage-gated $Na^+$ channels and massive inward sodium current.

Voltage-Gated Sodium Channels

Ion channels responsible for rapid cardiac conduction velocity in working muscle, which open and inactivate much faster than calcium channels.

Phase 1 in Cardiomyocytes

Brief, transient early repolarization resulting from rapid inactivation of voltage-gated sodium channels and brief potassium efflux.

Phase 2 (Plateau Phase)

The prolonged sustained depolarization phase where inward calcium influx through L-type channels balances outward potassium efflux.

Phase 3 in Cardiomyocytes

Rapid final repolarization driven by sustained outward potassium efflux through $K^+$ channels after calcium channels close.

Phase 4 in Cardiomyocytes

The stable resting membrane potential maintained primarily by background inward rectifier potassium currents.

SERCA2a

The sarcoplasmic/endoplasmic reticulum calcium ATPase pump that resequesters cytosolic calcium back into intracellular stores for muscle relaxation.

Troponin-C

The calcium-sensing subunit of the troponin regulatory complex on actin filaments that initiates cardiomyocyte mechanical cross-bridge contraction.

Refractory Period

The duration from ion channel inactivation following an action potential until channel recovery, during which another action potential cannot fire.

Inactivated Channel State

The closed, non-conducting conformation assumed by sodium or calcium channels immediately after opening, requiring membrane repolarization to reset.

Prolongation of Refractoriness via Potassium Blockade

Pharmacological inhibition of repolarizing $K^+$ channels, which extends action potential duration and delays channel reactivation.

Ectopic Pacemaker

An abnormal focus in the myocardium outside the SA node that fires spontaneous impulses faster than the intrinsic nodal rate.

Pulmonary Vein Ectopic Foci

Sleeve-like myocardial tissue around the pulmonary veins that frequently triggers ectopic beats initiating atrial fibrillation.

Left Ventricular End-Diastolic Pressure (LVEDP) Elevation

Increased filling pressure inside a dilated, failing ventricle that transmits backward tension into the left atrium.

Atrial Stretch-Induced Arrhythmogenesis

Mechanical distension of the atrial chamber walls that alters electrophysiological properties and stimulates ectopic impulse formation.

Atrial Fibrillation (AFib)

A supraventricular tachyarrhythmia characterized by chaotic, uncoordinated atrial excitation and loss of effective atrial mechanical systole.

Absent P Waves

The electrocardiographic absence of distinct atrial depolarization waves, diagnostic of atrial fibrillation.

Irregular R-R Intervals

An irregular distance between consecutive QRS complexes representing unpredictable, irregularly irregular ventricular responses in AFib.

Sarah's Presentation with AFib

Occurrence six months post-HFrEF diagnosis with sudden palpitations, generalized fatigue, and worsening shortness of breath.

Rate Control Strategy in AFib

A management goal aiming to restrict the number of irregular atrial impulses transmitted across the AV node into the ventricles.

Ventricular Filling Time in Tachycardia

The diastolic period necessary for passive ventricular filling, which becomes severely curtailed when ventricular rates are excessively fast.

AV Node Filtering Function

The intrinsic physiological delay within the atrioventricular node that prevents massive fibrillatory atrial frequencies from engaging ventricles.

Metoprolol in AFib Rate Control

A selective $\beta_1$-adrenergic receptor blocker that lowers AV nodal calcium currents via reduced cAMP/PKA signaling, slowing ventricular rate.

Contraindication of Diltiazem in Sarah

The clinical rule barring non-DHP CCBs in Sarah because their negative inotropic effect severely depresses systolic function in HFrEF.

Non-Dihydropyridine CCBs (Non-DHP CCBs)

Calcium channel blockers such as Diltiazem that target cardiac L-type channels, slowing AV conduction but markedly reducing contractility.

Rhythm Control Strategy in AFib

A therapeutic objective focused on terminating abnormal chaotic impulses in the atria to restore and maintain normal sinus rhythm.

Amiodarone

A broad-spectrum antiarrhythmic agent capable of blocking multiple cardiac ion channels used for atrial and ventricular rhythm management.

Amiodarone Ion Channel Targets

The pharmacological property of Amiodarone blocking sodium ($Na^+$), calcium ($Ca^{2+}$), and potassium ($K^+$) channels.

Amiodarone's Potassium Affinity

The drug's predominant clinical affinity for blocking repolarizing potassium channels, prolonging the effective refractory period.

Oral Amiodarone in AFib

The standard oral route used for maintenance rhythm control in atrial fibrillation to terminate erratic ectopic propagation.

Amiodarone Overdose Danger

The risk of totally arresting cardiac conduction or paradoxically inducing lethal proarrhythmias due to comprehensive pan-channel blockade.

Amiodarone Pulmonary Toxicity

A severe, potentially life-threatening adverse reaction resulting in widespread inflammatory and alveolar lung consolidation.

Reversibility of Amiodarone Toxicity

Resolution of pulmonary consolidations demonstrated on repeat chest radiography $45\text{ days}$ after stopping Amiodarone therapy.

Monomorphic Ventricular Tachycardia (VT)

A rapid ventricular rhythm where every QRS complex displays the exact same uniform morphological shape and configuration.

Sarah's Monomorphic VT Heart Rate

A sudden ventricular tachycardia at $170\text{ beats/min}$ arising three months after initial stabilization.

Uniform QRS Morphology

Identical beat-to-beat QRS complexes indicating that all abnormal ventricular impulses originate from a single distinct focal site or circuit.

P-Wave Disruption in Monomorphic VT

The loss of normal sinus P-waves, which appear merged directly into wide, independently firing QRS complexes.

Re-Entry Circuit

A continuous loop of unidirectional conduction block and slow propagation enabling an electrical wavefront to perpetually re-excite cardiac tissue.

Myocardial Scar Tissue in VT Pathogenesis

Inexcitable fibrous collagen formed after an infarction around which surviving ischemic pathways form an anatomical re-entrant loop.

Intravenous (IV) Amiodarone in VT

Acute parenteral administration to terminate ventricular tachycardia, presenting lower pulmonary toxicity risk due to shorter exposure time.

Lidocaine

A class IB antiarrhythmic that preferentially binds and blocks inactivated fast $Na^+$ channels in depolarized, ischemic cardiac myocardium.

Lidocaine Ischemic Selectivity

Higher drug binding affinity for depolarized, damaged myocytes, making it ideal during or immediately after acute myocardial infarction.

Flecainide and Encainide

Class IC sodium channel blockers strictly contraindicated in patients with previous myocardial infarction due to fatal proarrhythmia.

CAST (Cardiac Arrhythmia Suppression Trial)

A major clinical study demonstrating that Flecainide and Encainide increased all-cause mortality when used post-MI for ventricular arrhythmias.