Cardiovascular System

Angina spectrum

• Symptoms of angina typically appear once a coronary vessel is roughly 90% occluded; anginal pain classically lasts only a few minutes and produces transient ST-segment depression during the episode.
• Anti-anginal treatment for stable disease centers on nitrates, beta-blockers, and calcium channel blockers.
• Nitrates are converted to nitric oxide, causing venodilation that lowers preload (and modest coronary dilation); sublingual nitroglycerin is first-line for acute attacks, and longer-acting nitrates (e.g., isosorbide dinitrate) are used for prophylaxis; expect headache, tachyphylaxis, orthostatic hypotension, and flushing. Never combine nitrates with a PDE-5 inhibitor (e.g., sildenafil) — both raise cGMP through the same pathway, and the combination can cause severe, refractory hypotension; nitrates are also avoided in right ventricular infarction and hypertrophic cardiomyopathy, since both depend on adequate preload.
• Unstable angina is managed with anticoagulation (heparin, low-molecular-weight heparin, aspirin), nitrates, and beta-blockers; calcium channel blockers and thrombolytics are not appropriate for unstable angina.
• Cocaine can precipitate ischemia through coronary vasospasm by blocking reuptake of catecholamines (dopamine, norepinephrine, epinephrine, serotonin) at the synapse, in contrast to amphetamines, which stimulate catecholamine release.

Diagnostic testing for suspected chronic coronary disease

• Exercise (or pharmacologic) stress testing is a standard way to unmask subacute/chronic coronary occlusion that isn't apparent at rest.
• Thallium-201 perfusion scanning reveals regions of reduced perfusion (defects) during stress.
• Technetium-99m scanning is useful for imaging areas of prior infarction.

How antianginals reduce oxygen demand

Antianginal therapy works by lowering one or more of the determinants of myocardial oxygen consumption: end-diastolic volume, blood pressure, heart rate, and contractility.

• Because nitrates alone trigger reflex tachycardia and increased contractility, pairing them with a beta-blocker blunts that reflex and produces a larger net reduction in oxygen demand than either drug alone.
• Ranolazine is reserved for refractory angina: it inhibits the late inward sodium current, which indirectly reduces intracellular calcium overload and diastolic wall tension — without changing heart rate or blood pressure. Watch for constipation and QT prolongation.

Myocardial infarction

• Caused by a fixed occlusive thrombus over a ruptured plaque, cutting off perfusion to downstream myocardium.
• Subendocardial tissue is most vulnerable first, since it receives the least perfusion reserve during systole.

ECG localization of STEMI

Time course of infarction

• Cardiac troponin rises within a few hours, peaks around 24 hours, and stays elevated for roughly a week or more — the most sensitive/specific marker and the earliest to rise.
• CK-MB rises and falls faster than troponin, making it useful for detecting reinfarction within days of an initial event.
• AST and LDH rise later and more slowly, following behind troponin and CK-MB — historically used but now largely superseded by troponin.
• Because it preferentially blocks partially depolarized (ischemic) tissue over normal tissue — a state-dependent effect — IV lidocaine is useful for suppressing acute MI-associated ventricular arrhythmias.

Chronic ischemic patterns

• Myocardial hibernation: a chronically underperfused segment of viable myocardium downregulates its contractile function to match the reduced blood supply; this systolic dysfunction is potentially reversible with revascularization.
• Myocardial stunning: a brief episode of acute ischemia (e.g., after successful reperfusion) leaves transient, reversible contractile dysfunction even though blood flow has been restored.
• Coronary steal syndrome: distal to a fixed coronary stenosis, resistance vessels are already maximally dilated to compensate for reduced flow. Giving a vasodilator (dipyridamole, adenosine, regadenoson) dilates the healthy vessels further, dropping their resistance and diverting ("stealing") blood away from the already-maximally-dilated, stenosed territory — the basis of vasodilator stress testing, which detects this flow mismatch even though it can, rarely, provoke true ischemia.

Complications by timing

Post-MI management

• Revascularization (thrombolysis or percutaneous intervention) when timely.
• Antiplatelet therapy (aspirin), anticoagulation, nitrates, and analgesia acutely.
• Long-term secondary prevention: beta-blockers, ACE inhibitors, statins, and aspirin all reduce mortality/remodeling.

Left- vs. right-sided failure

Systolic vs. diastolic (HFrEF vs. HFpEF)

• HFrEF (reduced ejection fraction, systolic dysfunction): the ventricle can't contract normally, so ejection fraction falls and end-diastolic volume rises; classic causes are prior MI or dilated cardiomyopathy.
• HFpEF (preserved ejection fraction, diastolic dysfunction): ejection fraction stays roughly normal, but a stiff, poorly compliant ventricle (often from chronic hypertension-driven hypertrophy) can't fill properly, so filling pressures rise for a given volume.
• B-type natriuretic peptide (BNP), released by stretched ventricular myocytes in response to wall tension, is a useful blood test for diagnosing heart failure — a very good negative predictive value makes a low BNP helpful for ruling HF out.

Pathophysiologic loop

• This compensatory neurohormonal activation initially supports blood pressure but ultimately worsens congestion and remodeling — the rationale for RAA-axis blockade in treatment.

Pharmacologic management

• Digoxin's inotropic mechanism cascade: blocking the Na⁺/K⁺-ATPase raises intracellular sodium, which reduces the activity of the Na⁺/Ca²⁺ antiporter, which in turn raises intracellular calcium available for contraction.
• ACE inhibitor adverse effects include reversible renal insufficiency, hyperkalemia, angioedema, dry cough (bradykinin-mediated), and orthostatic hypotension; they are fetotoxic and contraindicated in pregnancy.
• Cor pulmonale is right-sided heart failure caused by a primary lung disorder that produces pulmonary arterial hypertension.
• High-output heart failure is an uncommon pattern where cardiac output is actually elevated but still can't meet the body's needs, because systemic vascular resistance has fallen sharply (severe anemia, hyperthyroidism, arteriovenous shunting/fistula, wet beriberi, advanced cirrhosis, severe obesity, or Paget disease of bone). It still presents with the same signs of venous congestion as low-output failure.
• Milrinone is a short-term IV inotrope/vasodilator for acute decompensated heart failure or cardiogenic shock: by inhibiting phosphodiesterase-3, it raises intracellular cAMP in the myocardium (↑ contractility) and in vascular smooth muscle (vasodilation). It is not used chronically, since long-term phosphodiesterase-3 inhibition increases mortality.

Normal ECG landmarks

• P wave: atrial depolarization.
• PR interval (0.12–0.20 s): atrial-to-ventricular conduction time, mostly reflecting AV nodal delay.
• QRS (< 0.10 s normally): ventricular depolarization.
• T wave: ventricular repolarization; inversion can indicate ischemia or a recent MI.
• U wave: a small deflection after the T wave, most notably prominent in hypokalemia (also seen with bradycardia).

Heart blocks

Tachyarrhythmia patterns

• Atrial fibrillation: chaotic, disorganized atrial activity with an irregularly irregular ventricular response; risk of atrial mural thrombus and embolic stroke.
• Atrial flutter: organized "sawtooth" atrial activity around 300/min with a regular conduction ratio (e.g., 2:1).
• Ventricular tachycardia: wide, regularly-shaped QRS complexes at a rapid rate; AV dissociation may be present.
• Ventricular fibrillation: chaotic, disorganized ventricular activity — a pulseless, life-threatening rhythm.
• Torsades de pointes: polymorphic VT with QRS amplitude that appears to twist around the baseline; associated with QT prolongation.
• Wolff–Parkinson–White: an accessory bypass tract preexcites the ventricle, producing a short PR interval and a slurred initial QRS upstroke (delta wave).

Premature beats

• Premature atrial contraction: an early beat from an ectopic atrial focus rather than the SA node; narrow QRS with a preceding (often abnormal-looking) P wave. Usually benign and often triggered by caffeine or adrenergic drive, though frequent PACs raise the risk of atrial fibrillation/flutter.
• Premature ventricular contraction: an early, wide QRS beat with no preceding P wave, arising from a ventricular focus; shortens diastolic filling time and so lowers that beat's stroke volume. Prognosis depends mainly on the underlying heart disease.

Sick sinus syndrome and hereditary channelopathies

• Sick sinus syndrome: age-related degeneration of the SA node producing bradycardia, sinus pauses, sinus arrest, or alternating brady-tachycardia; may need a pacemaker if symptomatic.
• Brugada syndrome: autosomal dominant, usually from a loss-of-function sodium channel mutation, more prevalent in males of Asian descent; ECG shows a pseudo-right-bundle-branch-block pattern with ST elevation in the right precordial leads (V1–V3) and confers a real risk of sudden cardiac death — managed with an implantable defibrillator.
• Congenital long QT syndrome: usually a loss-of-function potassium channel mutation impairing repolarization, predisposing to torsades de pointes. Romano-Ward syndrome is autosomal dominant with a purely cardiac phenotype; Jervell and Lange-Nielsen syndrome is autosomal recessive and adds sensorineural deafness.

Antiarrhythmic drug classes (Vaughan Williams)

• Digoxin's therapeutic ECG signature is distinct from toxicity: it increases the PR interval, decreases the QT interval, depresses the ST segment, and inverts the T wave.

Other antiarrhythmic agents

• Adenosine: transiently blocks AV nodal conduction by increasing potassium efflux and hyperpolarizing nodal tissue, effectively terminating reentry circuits that depend on the AV node; very short half-life (seconds); first-line for terminating reentrant supraventricular tachycardia and useful diagnostically to unmask atrial activity or distinguish a supraventricular from a ventricular origin of a wide-complex tachycardia. Side effects include flushing, transient hypotension, and chest pain.
• Digoxin: inhibits the myocyte Na⁺/K⁺-ATPase, indirectly raising intracellular calcium via the Na⁺/Ca²⁺ exchanger; increases contractility and slows AV conduction.
• Potassium: useful in digoxin toxicity with hypokalemia, since low potassium potentiates digoxin binding.

Rhythm-specific treatment approach

• Chronic atrial fibrillation predisposes to atrial thrombus with systemic embolization, so anticoagulation (e.g., warfarin) is used to prevent stroke.
• Diltiazem is particularly useful for controlling ventricular rate in atrial fibrillation because it slows AV nodal conduction.

Digoxin toxicity

• Presents with GI symptoms, visual disturbances (yellow-green halos), confusion, and dangerous arrhythmias.
• Toxicity risk rises with renal impairment (reduced clearance), hypokalemia (potentiates binding), and quinidine (displaces digoxin from tissue binding sites and reduces its clearance).
• Management: repeated-dose activated charcoal; avoid giving calcium in associated hyperkalemia, since it can worsen intracellular calcium overload; give atropine if bradycardia is present; treat hyperkalemia only if it is producing ECG changes.
• Digoxin-specific antibody fragments (Fab) are reserved for severe toxicity — hemodynamic instability, life-threatening arrhythmia or severe bradycardia unresponsive to atropine, markedly elevated potassium or digoxin level, a large ingested dose, or a digoxin-toxic rhythm with an elevated level.

Adverse effects by antiarrhythmic class

• Class IA: quinidine causes cinchonism (headache, tinnitus, thrombocytopenia); procainamide can cause a reversible lupus-like syndrome; both risk torsades de pointes.
• Class IB: CNS stimulation/depression is common to the group; long-term tocainide use can also cause neutropenia and thrombocytopenia.
• Class IC: proarrhythmic, especially post-MI — avoided in structural/ischemic heart disease.
• Class II (beta-blockers): bradycardia, AV block, bronchospasm, heart failure exacerbation, sedation, sleep disturbance; class II and class III agents are the antiarrhythmic groups shown to reduce mortality, whereas most other antiarrhythmics can themselves be proarrhythmic.
• Class III: amiodarone carries broad, distinctive toxicity beyond its class III action — pulmonary fibrosis, corneal deposits, hepatotoxicity, skin discoloration/photodermatitis, thyroid dysfunction (more often hypothyroidism), and neurologic effects, in addition to bradycardia/heart block.
• Class IV (non-dihydropyridine CCBs): constipation, flushing, peripheral edema, AV block, sinus node depression.

Beyond the antiarrhythmics themselves, a wide range of other drug classes can prolong the QT interval and predispose to torsades de pointes — remembered with "ABCDEF+NO": Antiarrhythmics (class IA/III), Arsenic, Biotics (macrolides, fluoroquinolones), Cychotics (haloperidol), Chloroquine, Depressants (TCAs), Diuretics (thiazides), Emetics (ondansetron), Fungals (fluconazole), protease iNhibitors, Opioids (methadone).

Classification

• Essential (primary) hypertension: accounts for roughly 95% of cases; multifactorial, no single identifiable cause; diagnosed after blood pressure is found above 140/90 mm Hg on three separate occasions with the patient seated comfortably.
• Secondary hypertension: attributable to an identifiable condition.

Hypertensive urgency vs. emergency

• Both involve severely elevated blood pressure (roughly ≥180/120 mm Hg).
• Urgency: no acute end-organ damage.
• Emergency: evidence of acute end-organ damage — encephalopathy, aortic dissection, pulmonary edema, acute kidney injury, papilledema.
• Emergencies require controlled IV blood-pressure reduction (e.g., nitroprusside, labetalol, nicardipine, clevidipine, or fenoldopam) rather than pure beta-blockade, since unopposed alpha stimulation can worsen vasoconstriction.
• Malignant (emergency) hypertension is a major cause of early death via cerebrovascular accident and has classically been described as disproportionately affecting young Black men.

Chronic end-organ effects of hypertension

• Left ventricular hypertrophy (also seen with aortic stenosis and mitral regurgitation).
• Arteriolosclerosis ("hyaline" or "hyperplastic onion-skinning" of small vessel walls).
• Retinal hemorrhages/exudates.

Antihypertensive drug classes

Beta-blocker effects by organ system

• Beyond hypertension, beta-blockers are used for stable angina, post-MI prophylaxis, symptomatic control of hyperthyroidism, migraine prophylaxis, and anxiety disorder.
• Nonselective alpha-blockers (phenoxybenzamine, phentolamine) are used specifically to manage pheochromocytoma before and during surgery.

Choosing an antihypertensive by comorbidity

Atherogenesis

• The lipid-rich necrotic core is the most cholesterol-dense part of an established plaque.
• Plaque rupture exposes thrombogenic material, triggering platelet aggregation and acute thrombosis.
• Complications: occlusive thrombosis (MI, stroke), aneurysmal weakening of the wall, embolization of plaque debris, renal arterial ischemia, and death.

Risk factors

Familial dyslipidemia patterns

• Type IIb (combined hyperlipidemia) and type IV (hypertriglyceridemia) are the two most common familial dyslipidemia patterns overall.

Lipid-lowering agents

Physical signs of hyperlipidemia

• Xanthomas: lipid-laden plaques or nodules in the skin, especially around the eyelids (xanthelasma).
• Tendinous xanthoma: lipid deposits in tendons, classically the Achilles tendon — a clue for familial hypercholesterolemia.
• Corneal arcus: a lipid ring at the edge of the cornea; common and benign in older adults (arcus senilis), but suggests hypercholesterolemia when it appears at a younger age.

Systolic murmurs

Diastolic murmurs

• Maneuvers that increase venous return/preload (squatting, leg raise) or afterload (handgrip) tend to intensify regurgitant and stenotic left-heart murmurs, while maneuvers that reduce preload (standing, Valsalva strain) intensify the hypertrophic cardiomyopathy murmur and mitral valve prolapse click.

Maneuver effects, in more detail

Pressure–volume loop changes by lesion

• Idiopathic dilated cardiomyopathy is the most common form of cardiomyopathy overall; management includes digitalis, ACE inhibitors, heart transplantation, and sometimes chronic anticoagulation given the embolic risk.

Hypertrophic obstructive cardiomyopathy (HOCM)

• The subset of hypertrophic cardiomyopathy where asymmetric septal hypertrophy plus systolic anterior motion of the mitral valve obstructs the left ventricular outflow tract during systole — producing dyspnea and, in severe cases, exertional syncope.
• Because outflow obstruction worsens with a smaller, more vigorously contracting ventricle, drugs that reduce preload (diuretics, vasodilators) make symptoms worse and are avoided; high-intensity athletic activity is also avoided given the sudden-death risk.
• First-line treatment is a beta-blocker or a non-dihydropyridine CCB; the myosin inhibitor mavacamten is used for refractory symptoms, and an implantable defibrillator is added for patients at high risk of sudden death.

Stress (takotsubo) cardiomyopathy

• Transient apical ballooning of the left ventricle, likely from a surge of catecholamines during acute emotional or physical stress ("broken heart syndrome").
• Mimics an acute coronary syndrome clinically but occurs without obstructive coronary disease; usually reversible with supportive care.

Myocarditis

• Inflammation of the myocardium, most often viral — coxsackievirus B is the classic and most common cause of neonatal myocarditis; parvovirus B19 and human herpesvirus 6 are other common viral causes.
• HIV can cause myocarditis indirectly through opportunistic toxoplasmosis or cardiac involvement by Kaposi sarcoma.
• Bacterial causes include Staphylococcus aureus, Corynebacterium diphtheriae, and tuberculosis.
• Other causes: Chagas disease (Trypanosoma cruzi, transmitted by the reduviid/"kissing" bug), Lyme disease (Borrelia burgdorferi, transmitted by the Ixodes tick — stage 1 causes erythema chronicum migrans, stage 2 brings cardiac and neurologic involvement, stage 3 brings arthritis), hypersensitivity reactions, sarcoidosis.
• Findings: muffled S1, S3 gallop, mitral regurgitation murmur, cardiomegaly; can progress to dilated cardiomyopathy and arrhythmia.

Infective endocarditis

• Vegetations of organisms, platelets, and fibrin form on heart valves, most often on the mitral or aortic valve (tricuspid involvement suggests IV drug use).
• Classic peripheral findings: Janeway lesions (painless erythematous macules), Osler nodes (painful, tender nodules), splinter hemorrhages, Roth spots, and conjunctival petechiae — reflecting immune complex deposition and septic emboli.

• Blood-culture-negative endocarditis can result from the fastidious HACEK group of organisms.
• Endocarditis caused by Streptococcus bovis should prompt evaluation for an underlying gastrointestinal malignancy.
• Prosthetic heart valves predispose to endocarditis caused by Staphylococcus epidermidis.

Rheumatic heart disease

• A delayed immune-mediated sequela of pharyngitis caused by group A streptococcus, driven by molecular mimicry between streptococcal and cardiac antigens.
• Acute rheumatic fever mainly affects children; can involve all layers of the heart (pancarditis), including pericarditis with effusion; myocarditis is the leading cause of early death in the acute phase.
• Endocarditis in rheumatic fever affects valves in a characteristic order — mitral, then aortic, then tricuspid, then pulmonary — with the mitral valve most often involved overall; repeated episodes cause chronic fibrotic, stenotic valve disease.
• Characteristic histology: the Aschoff body, a focus of fibrinoid necrosis with activated macrophages (Anitschkow cells) and giant cells.
• Extracardiac features: migratory polyarthritis, subcutaneous nodules, erythema marginatum, and Sydenham chorea.
• Diagnosis is supported by evidence of a recent group A streptococcal infection, most often an elevated antistreptolysin-O (ASO) titer.

Aneurysm types

Abdominal aortic aneurysm (AAA)

• Focal dilation of the infrarenal aorta, most often atherosclerotic.
• Often asymptomatic until rupture; can present with vague abdominal pain and is easily mistaken for kidney stones in the emergency setting.
• Classic rupture triad = hypotension, abdominal/back pain, pulsatile abdominal mass.
• One-time ultrasound screening is recommended for men aged roughly 65–75 with any smoking history.
• Surgical repair is generally offered for a diameter ≥5.5 cm, growth ≥0.5 cm over 6 months, or any symptomatic aneurysm.

Aortic dissection

• An intimal tear allows blood to dissect into the media, creating a false lumen.
• Hypertension is the dominant risk factor; connective tissue disorders (Marfan, Ehlers-Danlos) and prior trauma also predispose.
• Classified by whether the ascending aorta is involved: dissections involving the ascending aorta need urgent surgery; those confined to the descending aorta are usually managed medically unless complicated.
• Presentation: sudden, severe, tearing chest/back pain; widened mediastinum on chest x-ray.
• Initial management: rapid heart-rate and blood-pressure control (e.g., IV beta-blocker) before any further workup or intervention.

Traumatic aortic rupture & subclavian steal

• Traumatic aortic rupture: a sudden deceleration injury (motor vehicle collision, major fall) shears the aorta most often at the aortic isthmus, just distal to the left subclavian artery origin; chest x-ray classically shows a widened mediastinum.
• Subclavian steal syndrome: stenosis of the subclavian artery proximal to the vertebral artery origin causes blood to flow backward down the ipsilateral vertebral artery to supply the arm during exertion, "stealing" from the posterior cerebral circulation. Presents with arm ischemia/paresthesia plus vertebrobasilar symptoms (dizziness, vertigo) on exertion of the affected arm, and a systolic blood pressure difference >15 mm Hg between arms. Most often atherosclerotic, but can follow Takayasu arteritis or cardiac surgery.

Cholesterol embolization syndrome

• Cholesterol crystals dislodge from an atherosclerotic plaque (usually in the aorta) and shower into small distal arteries — classically after an invasive vascular procedure like angiography or angioplasty.
• Produces end-organ damage from small-vessel occlusion plus an inflammatory response: livedo reticularis, blue/discolored toes, acute kidney injury, stroke, or bowel ischemia.
• Because only small distal vessels are affected, proximal pulses typically remain palpable — a useful distinction from large-vessel thromboembolism.

Deep venous thrombosis

• A clot forms within a deep vein, producing unilateral limb swelling, redness, warmth, and pain.
• Predisposed by Virchow triad — Stasis (immobility, long travel, postoperative state), hypercoagulability (factor V Leiden and other clotting-cascade defects, oral contraceptives, pregnancy), and endothelial damage (exposed collagen activates the clotting cascade).
• Embolization risk is highest for proximal (femoral, iliac, popliteal) clots; isolated distal calf DVTs are less likely to embolize and often resolve on their own.
• A D-dimer test has good sensitivity to rule out DVT when pretest probability is low, but poor specificity; compression ultrasound with Doppler is the imaging test of choice.
• Heparin (unfractionated or low-molecular-weight) is used for prophylaxis and acute management; direct oral anticoagulants are used for ongoing treatment and prevention.

By vessel size

Small vessel

• Granulomatosis with polyangiitis (Wegener): c-ANCA positive; more common in males; classic triad of necrotizing vasculitis, necrotizing granulomas of the respiratory tract, and necrotizing glomerulitis; presents with cough, sinus/nasal septum ulceration, and red blood cell casts in the urine.
• Eosinophilic granulomatosis with polyangiitis (Churg-Strauss): p-ANCA positive; asthma, eosinophilia, and vasculitis.
• IgA vasculitis (Henoch-Schönlein purpura): children, often atopic and following an upper respiratory infection; hemorrhagic urticaria, palpable purpura, arthralgia, abdominal pain, and IgA-mediated renal disease with red blood cell casts.

Not a true vasculitis but relevant

• Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu): autosomal dominant; fragile telangiectatic vessels causing recurrent epistaxis and GI bleeding; notably more common in Utah's Mormon population due to a founder effect.
• Kaposi sarcoma: HHV-8–driven vascular neoplasm, classically in the setting of advanced HIV/AIDS.

Heart position, pericardium & coronary blood supply

• The left atrium forms the most posterior part of the heart — an enlarged left atrium (e.g., mitral stenosis) can compress the esophagus (causing dysphagia) or the left recurrent laryngeal nerve (causing hoarseness, called Ortner syndrome).
• The right ventricle is the most anterior chamber and so is the structure most often injured in penetrating chest trauma; on the diaphragmatic (inferior) surface, the left ventricle makes up roughly two-thirds and the right ventricle roughly one-third.
• The pericardium has three layers, outer to inner: fibrous pericardium, parietal (serous) pericardium, and epicardium (visceral pericardium) — with the pericardial space in between. The pericardium is innervated by the phrenic nerve, which is why pericarditis can refer pain to the neck, shoulder, or arm.
• The left anterior descending (LAD) artery supplies the anterior two-thirds of the interventricular septum, the anterolateral papillary muscle, and the anterior LV wall — it is the vessel most often occluded in MI.
• The posterior descending artery (PDA) supplies the posterior third of the septum, the posterior two-thirds of the ventricular walls, the posteromedial papillary muscle, and (usually) the SA and AV nodes; an infarct here can cause nodal dysfunction such as bradycardia or heart block.
• Coronary "dominance" refers to which vessel gives rise to the PDA: right-dominant (PDA from the RCA) is most common, left-dominant (PDA from the LCX) occurs in roughly 5–10%, and codominant circulation (PDA from both) in roughly 10–20%.
• The right (acute) marginal artery supplies the right ventricle; the coronary sinus runs in the left atrioventricular groove and drains into the right atrium, and normally carries the most deoxygenated blood in the body.
• Coronary blood flow to the left ventricle and interventricular septum peaks in early diastole, when the myocardium is relaxed and not compressing its own vessels — unlike most other organs, which are perfused mainly during systole.

Electrical conduction pathway

• The SA node is the dominant pacemaker because it has the fastest intrinsic rate of spontaneous phase-4 depolarization.
• Nodal tissue (SA, AV) depolarizes via slow inward calcium current; working atrial/ventricular myocardium depolarizes via fast sodium current.
• The AV node deliberately conducts slowly, which (1) lets the atria finish contracting and empty into the ventricles before ventricular systole and (2) protects the ventricles from excessively fast atrial rates.
• Conduction velocity tracks the steepness (upstroke) of phase 0, not the total duration of the action potential.
• The SA node sits in the upper crista terminalis near the SVC; the AV node sits in the interatrial septum near the opening of the coronary sinus and is supplied by the PDA (hence the nodal dysfunction seen with inferior/PDA-territory infarcts).
• Intrinsic pacemaker rate, fastest to slowest: SA node > atria > AV node > bundle of His/Purkinje fibers/ventricles — this hierarchy is what allows a slower "escape" pacemaker to take over if a faster one fails.
• Conduction velocity, fastest to slowest: His-Purkinje system > atria > ventricles > AV node (mnemonic: "He Parks At Ventura Avenue").

Pacemaker vs. myocardial action potentials

• Acetylcholine and adenosine slow phase-4 depolarization (↓ heart rate); catecholamines speed it up (↑ heart rate) by increasing the likelihood that HCN channels are open.
• Because the fast Na⁺ channels in nodal cells are permanently inactivated at their less-negative resting potential, the AV node relies on the slower Ca²⁺-driven upstroke — the cellular basis for its role in intentionally delaying transmission from atria to ventricles.

Chronotropy, inotropy, and loading conditions

Cardiac cycle — phase by phase

1. Isovolumetric contraction: mitral valve closes → aortic valve opens; ventricular volume constant, pressure rising steeply; peak myocardial oxygen demand.
2. Ejection: aortic valve open, blood leaves ventricle, volume falls.
3. Isovolumetric relaxation: aortic valve closes → mitral valve opens; volume constant, pressure falling.
4. Rapid filling: immediately after mitral valve opens.
5. Reduced (diastasis) filling: passive filling slows just before atrial systole.

• Heart sounds: S1 = mitral/tricuspid closure (start of systole); S2 = aortic/pulmonic closure (start of diastole); S3 = rapid ventricular filling (normal in youth, pathologic in volume overload/heart failure); S4 = atrial contraction against a stiff ventricle.
• Jugular venous waveform: a wave = atrial contraction; c wave = tricuspid bulging into the atrium during isovolumetric ventricular contraction; v wave = atrial filling against a closed tricuspid valve.
• On the pressure–volume loop: increased contractility raises stroke volume/ejection fraction and lowers end-systolic volume; increased afterload lowers stroke volume and raises end-systolic volume; increased preload raises stroke volume (Frank–Starling).

Frank–Starling (contractility) curves

• Plotting stroke volume (or cardiac output) against ventricular end-diastolic volume (preload) gives the Frank–Starling curve: within physiologic limits, more stretch produces a stronger contraction.
• Positive inotropes (catecholamines, digoxin, exercise) shift the whole curve upward and to the left — more output for the same preload.
• Loss of functional myocardium (e.g., after MI), acute beta-blockade, non-dihydropyridine CCBs, and heart failure shift the curve downward and to the right — less output for the same preload.
• A failing heart placed back on a positive inotrope moves partway back up toward — but usually not fully onto — the normal curve.

Splitting of S2

Neurohormonal regulation

• Baroreceptors in the carotid sinus and aortic arch sense stretch; carotid input travels via CN IX, aortic arch input via CN X, both relaying to the nucleus tractus solitarius in the medulla.
• Rising pressure → increased vagal (parasympathetic) tone → slower heart rate and lower pressure; falling pressure has the opposite effect, and this baroreceptor reflex is the body's key acute compensation for hypovolemic shock.
• Carotid sinus hypersensitivity — an exaggerated response to gentle pressure over the carotid sinus (tight collar, shaving, carotid massage) — can trigger enough reflex bradycardia and vasodilation to cause presyncope or syncope; risk rises with atherosclerosis, prior neck surgery, or older age.
• Peripheral chemoreceptors (carotid and aortic bodies) respond to a falling PO₂ (below roughly 60 mm Hg), a rising PCO₂, and a falling pH. Central chemoreceptors in the medulla respond only to CO₂/pH changes in brain interstitial fluid, not directly to oxygen, and become progressively less sensitive with chronic CO₂ retention (e.g., COPD) — shifting the drive to breathe onto the peripheral (hypoxic) chemoreceptors.
• The Cushing reflex is a triad of hypertension, bradycardia, and irregular respiration seen with rising intracranial pressure: cerebral ischemia raises sympathetic tone and blood pressure, and the resulting stretch then triggers a baroreceptor-mediated reflex bradycardia.
• Atrial natriuretic peptide is released by stretched atrial myocytes and counteracts the renin-angiotensin-aldosterone (RAA) axis: it promotes natriuresis, vasodilation, and inhibits renin.
• Antidiuretic hormone (vasopressin) increases free-water reabsorption in the collecting duct and constricts arterioles, raising both volume and resistance.

Local blood flow autoregulation

Most organs adjust their own vascular tone to keep blood flow roughly constant across a range of perfusion pressures, largely through locally produced vasodilator metabolites.

Capillary fluid exchange

• Fluid movement across the capillary wall is governed by the balance of four Starling forces: capillary hydrostatic pressure (pushes fluid out), interstitial hydrostatic pressure (pushes fluid in), plasma oncotic pressure (pulls fluid in), and interstitial oncotic pressure (pulls fluid out).
• Edema results when this balance shifts toward net outward flow: raised capillary hydrostatic pressure (e.g., heart failure), raised capillary permeability (toxins, infection, burns), raised interstitial oncotic pressure (lymphatic blockage), or reduced plasma oncotic pressure (nephrotic syndrome, liver failure, malnutrition).

Key equations

• Resistances in series add directly; resistances in parallel combine reciprocally, so recruiting parallel capillary beds lowers overall resistance.
• Myocardial oxygen demand rises with contractility, afterload, heart rate, and ventricular wall tension; the coronary sinus normally carries the most deoxygenated blood in the body, reflecting how much oxygen the heart itself extracts.
• Pulmonary capillary wedge pressure (PCWP), measured via a Swan-Ganz catheter, approximates left atrial pressure and left ventricular end-diastolic pressure — except in mitral stenosis, where the stenotic valve makes PCWP read higher than the true LVEDP.
• Pulse pressure widens in aortic regurgitation, age-related aortic stiffening (isolated systolic hypertension), obstructive sleep apnea, and high-output states (anemia, hyperthyroidism, transient with exercise); it narrows in aortic stenosis, cardiogenic shock, cardiac tamponade, and advanced heart failure.

Origin & early folding

• Heart tissue arises from splanchnic mesoderm.
• Two endocardial tubes form cranially and fuse into a single tube as the embryo folds.
• Folding brings the tube into the thorax, ventral to the foregut.

Five dilations of the primitive heart tube

Septation

• Two overlapping atrial septa (septum primum, septum secundum) build the interatrial wall.
• Their offset openings create the foramen ovale, a right-to-left shunt in fetal life.
• Fetal pulmonary vascular resistance is high, so right atrial pressure exceeds left — blood crosses the shunt rather than entering collapsed fetal lungs.
• At birth, lung expansion drops pulmonary resistance, left atrial pressure rises above right, and the septa are pressed together, functionally sealing the shunt.
• Interventricular septum forms from muscular ingrowth below plus membranous contributions from the spiral (aorticopulmonary) septum, the right and left bulbar ridges, and the endocardial (AV) cushions above.
• Abnormal development of the aorticopulmonary/spiral septum underlies tetralogy of Fallot, transposition of the great vessels, and persistent truncus arteriosus.

Valve development

• The aortic and pulmonary (semilunar) valves form from endocardial cushions within the outflow tract.
• The mitral and tricuspid (AV) valves form from the fused endocardial cushions of the AV canal.
• Valve anomalies from this process range from stenotic or regurgitant leaflets to a frankly absent (atretic) valve or an abnormally displaced one.

Aortic arch derivatives

• The paired dorsal aortae run the length of the embryo and fuse in the midline to form the descending aorta.

Venous system

• Vitelline veins → ductus venosus, hepatic sinusoids, portal vein, superior and inferior mesenteric veins, and part of the IVC.
• Umbilical veins: only the left persists prenatally, carrying oxygenated placental blood to the fetus via the ductus venosus; it becomes the ligamentum teres hepatis after birth. The right umbilical vein regresses entirely.
• Cardinal veins: anterior → superior vena cava/internal jugular system; posterior → inferior vena cava, azygos system, renal and common iliac veins.

Fetal circulation shunts

• Ductus arteriosus patency is maintained by locally produced prostaglandin E2 and low fetal oxygen tension.
• After birth, rising oxygen tension and falling prostaglandin levels drive functional closure within the first days of life.
• Clinically: indomethacin (a prostaglandin-synthesis inhibitor) helps close a patent ductus; exogenous prostaglandin E1 keeps it open when systemic or pulmonary flow depends on the shunt.
• Umbilical arteries carry deoxygenated fetal blood to the placenta — one of the few arterial systems in the body that does not carry oxygenated blood, along with the pulmonary arteries.

Congenital heart defects — quick reference

Other cyanotic (right-to-left) lesions

A simple way to remember the classic right-to-left ("blue baby") lesions is by vessel count in the name — truncus arteriosus (1 vessel), transposition (2 switched vessels), tricuspid atresia (3 = "tri"), tetralogy of Fallot (4 = "tetra"), and total anomalous pulmonary venous return (5 letters).

Congenital defect associations

Cardiac tumors

• Metastatic tumors to the heart are far more common than primary cardiac tumors.
• Myxoma: the most common primary cardiac tumor in adults, usually arising in the left atrium; can cause a "ball-valve" obstruction of the mitral orifice, syncope, and constitutional symptoms.
• Rhabdomyoma: the most common primary cardiac tumor in children; associated with tuberous sclerosis; histologically shows characteristic "spider cells" with glycogen-rich vacuoles.

Pericarditis

• Most often idiopathic or viral (coxsackievirus A or B, producing serous pericarditis); also tuberculosis (hemorrhagic pericarditis), uremia (serofibrinous), SLE and scleroderma (serous), and post-MI (Dressler syndrome, fibrinous).
• Sharp, pleuritic chest pain that worsens lying flat/with inspiration and improves sitting forward; pericardial friction rub; jugular venous distension that rises further with inspiration (Kussmaul sign); distant heart sounds; diffuse ST elevation on ECG.
• Unlike an MI, the ST elevation of pericarditis is diffuse across leads rather than confined to the distribution of one coronary territory, and is not accompanied by the reciprocal QRS changes seen in infarction.
• Chronic/recurrent pericarditis can progress to constrictive pericarditis, which mimics right-sided heart failure due to a rigid, non-compliant, calcified pericardium obliterating the pericardial cavity.

Jugular venous waveform abnormalities

Cardiac tamponade

• Fluid accumulation in the pericardial space compresses the heart, limiting ventricular filling; the most common causes are neoplasm, idiopathic pericarditis, and uremia.
• Classic findings: elevated intracardiac/intrapericardial pressure, reduced cardiac output, muffled heart sounds, and jugular venous distension (Beck triad along with hypotension).
• Pulsus paradoxus: an exaggerated (>10 mm Hg) inspiratory drop in systolic blood pressure. Mechanistically, inspiration increases venous return to the right ventricle, but with a non-compliant pericardium the interventricular septum bows into the left ventricle instead, reducing left ventricular filling and stroke volume. Beyond tamponade, this same pattern is seen in constrictive pericarditis and obstructive airway disease (croup, obstructive sleep apnea, asthma/COPD) — remembered as "COAT."
• Echocardiography shows a pericardial effusion along with systolic collapse of the right atrium, diastolic collapse of the right ventricle, and a plethoric, non-collapsing IVC; the ECG may show low voltage and electrical alternans from the heart swinging within the effusion.
• Treatment is pericardiocentesis to relieve the compression; the needle traverses skin, superficial fascia, pectoralis major, the intercostal muscle layers, and the fibrous and parietal serous pericardium.

• Shock = a state in which oxygen delivery fails to meet tissue metabolic demand.
• Common signs: tachycardia, hypotension, oliguria, altered mental status, weak pulses.

• Coronary (and renal, cerebral) blood flow is normally autoregulated to match local tissue metabolic demand, mediated in part by nitric oxide and adenosine.
• Sustained shock produces characteristic end-organ injury: acute tubular necrosis in the kidney, neuronal necrosis in the brain, fatty change in the heart and liver, patchy hemorrhage in the colon, and pulmonary edema from acute lung injury.

• Thrombotic risk: estrogen-containing oral contraceptives increase venous thromboembolic risk.
• Direct cardiotoxicity: anthracyclines (doxorubicin, daunorubicin) cause dose-dependent, largely irreversible cardiomyopathy; tricyclic antidepressants and lithium can also impair cardiac conduction/function.
• QT prolongation / torsades risk: class IA and class III antiarrhythmics, and tricyclic antidepressants.