Free USMLE Step 1 Cardiovascular practice questions

The flank ecchymosis, supratherapeutic INR and back pain after a fall suggest a retroperitoneal hemorrhage, and the hemodynamic profile is classic for hypovolemic shock.

Shock is classified by three levers: preload (PCWP), cardiac output and systemic vascular resistance. Reading SVR first, it is high, so this is a "cold" shock (cool, clammy skin from compensatory vasoconstriction). Within cold shock, the low PCWP and low right atrial pressure (flat neck veins, clear lungs) show an empty tank rather than a failing pump. Blood loss lowers mean systemic filling pressure and venous return, so preload and cardiac output fall. Baroreceptor unloading raises sympathetic outflow, producing tachycardia and arteriolar constriction that raise SVR. Low flow makes tissues extract more O2, so mixed venous saturation falls.

A. Cardiogenic shock also has low output, high SVR and low mixed venous saturation, but the failing pump causes a high PCWP with pulmonary congestion.

C. Neurogenic shock (for example, after spinal cord injury from a fall) loses sympathetic tone, so SVR is low and the patient is warm and bradycardic, not cold and tachycardic.

D. Obstructive shock from tamponade or tension pneumothorax raises right atrial pressure and distends the neck veins; tamponade also equalizes diastolic pressures and raises PCWP.

E. Septic shock is a distributive, "warm" shock with low SVR, often high cardiac output early, and a high mixed venous saturation from impaired extraction.

Statins competitively inhibit HMG-CoA reductase, the rate-limiting enzyme that converts HMG-CoA to mevalonate. The resulting fall in hepatocyte cholesterol is sensed in the endoplasmic reticulum, and the sterol-sensing transcription factor SREBP-2 is transported to the Golgi, cleaved, and moves to the nucleus. There it increases transcription of the LDL receptor gene. More receptors on the hepatocyte surface take up circulating LDL, which is why statins lower LDL by 20% to 60%, more than any other oral class, and reduce cardiovascular and all-cause mortality. The modest fall in triglycerides and rise in HDL are minor effects.

A. Decreased VLDL assembly from impaired apoB lipidation describes lomitapide, which inhibits microsomal triglyceride transfer protein and lowers LDL without LDL receptors. B. Increased lipoprotein lipase activity is the main action of fibrates, which mostly lower triglycerides. C. Decreased PCSK9 synthesis is the opposite of what statins do: SREBP-2 also drives PCSK9 transcription, so statins raise PCSK9 and partly blunt their own effect, which is why adding a PCSK9 inhibitor is synergistic. E. Decreased intestinal cholesterol absorption is the effect of ezetimibe through NPC1L1 blockade; statins act on synthesis, not absorption.

A pure positive inotrope lifts the cardiac function (Frank-Starling) curve: at any given right atrial pressure (preload), the ventricle ejects more blood. Because the drug does not change blood volume, venous tone or arteriolar resistance, the venous return curve stays where it is (same MSFP, same slope).

The new steady state is where the higher cardiac curve crosses the unchanged venous return curve. Moving up along a venous return line means moving to the left, so the new point has a higher cardiac output and a lower right atrial pressure. Physiologically, the stronger ventricle empties more completely, draws blood out of the right atrium and lowers RAP, which widens the gradient (MSFP minus RAP) that drives venous return. The rule of thumb: inotropy moves CO and RAP in opposite directions. Clinical examples include sympathetic beta1 stimulation, dobutamine and digoxin.

A. A rise in both CO and RAP is the signature of a volume load or venoconstriction (parallel right shift of the venous return curve). C. A fall in CO with a rise in RAP is negative inotropy, as in systolic heart failure or beta-blockade. D. A fall in both is hemorrhage, dehydration or venodilation (parallel left shift). E. A rise in CO with RAP about unchanged is the pattern of a fall in TPR, which rotates the venous return curve and also lifts the cardiac curve by lowering afterload; the stem rules out any change in vascular resistance.

A flat pink-purple patch that is fully present at birth and unilateral on the face is a port-wine stain (nevus flammeus), a capillary malformation. Most carry a somatic activating GNAQ mutation. The key biologic distinction is between vascular tumors and vascular malformations. Malformations are errors in forming vessels: they are present at birth, have no proliferative phase, grow only in proportion to the child, and never involute. Over decades a port-wine stain typically darkens and thickens, and it may become nodular. Pulsed-dye laser can lighten it. A lesion in the ophthalmic (V1) distribution would raise concern for Sturge-Weber syndrome with an ipsilateral leptomeningeal malformation and glaucoma; this lesion spares the forehead and eyelids.

B describes infantile hemangioma, a true endothelial tumor (GLUT1-positive) that is absent or faint at birth, proliferates for 3 to 5 months and then involutes over years. C describes the midline salmon patch (stork bite) on the nape or glabella, which usually fades. D is typical of pyogenic granuloma, a friable lobular capillary hemangioma. E is wrong because port-wine stains are not premalignant; angiosarcoma arises in sun-damaged scalp, irradiated skin, lymphedematous limbs or the liver.

This patient has drug-induced long QT with torsades de pointes. High-dose methadone and ondansetron both block the rapid delayed-rectifier potassium current (IKr, the hERG channel), and her risk is multiplied by hypokalemia and hypomagnesemia from gastroenteritis, bradycardia and female sex.

With IKr blocked, phase 3 repolarization slows and the ventricular action potential lengthens, seen as a long QT. During this prolonged plateau (phase 2) and early phase 3, L-type calcium channels recover from inactivation and reopen, producing an inward current that depolarizes the membrane before repolarization is complete. These early afterdepolarizations (EADs), which are favored by slow heart rates and long pauses, can reach threshold and fire premature beats; because repolarization is uneven across the myocardium, the beats propagate as a polymorphic VT whose axis twists around the baseline. Treatment is IV magnesium sulfate even with normal serum magnesium, potassium repletion, stopping the QT drugs, and pacing or isoproterenol for pause-dependent recurrences.

A, delayed afterdepolarizations, occur after repolarization is complete and are caused by calcium overload of the sarcoplasmic reticulum, as in digoxin toxicity; they produce bidirectional VT or atrial tachycardia with block. B, accessory pathway reentry, causes orthodromic or antidromic reentrant tachycardia in Wolff-Parkinson-White syndrome. C is wrong because she is bradycardic, and increased sinus automaticity produces sinus tachycardia, not polymorphic VT. E, fast sodium channel blockade (class IC drugs, tricyclic overdose), widens the QRS complex and promotes monomorphic VT rather than lengthening the QT.

This man has cardiac tamponade from rupture of the left ventricular free wall, a complication 3 to 14 days after a transmural infarct, presenting with Beck triad (hypotension, distended neck veins, muffled heart sounds), tachycardia, and right-sided chamber collapse. The pericardial pressure-volume curve is flat at first and then turns nearly vertical. The fibrous pericardium stretches only slowly, so when fluid accumulates over weeks the sac can accommodate more than 1 L at modest pressure. When blood enters suddenly, the pericardium has no time to stretch, and as little as 150 to 200 mL drives intrapericardial pressure above the filling pressures of the thin-walled right heart chambers. Diastolic filling, stroke volume, and blood pressure then fall, producing obstructive shock. For the same reason, removing a small volume by drainage can be lifesaving.

B. A thickened, fibrotic pericardium causes constrictive pericarditis, a chronic process; a pericardium 4 days after an MI is not fibrotic. C. The viscosity of the fluid does not determine intrapericardial pressure; volume and rate of accumulation relative to compliance do. D. Infarct-related pump failure causes cardiogenic shock with pulmonary edema, not chamber collapse on echo. E. Hypovolemia would produce flat neck veins and a falling hemoglobin, not distended jugular veins.

Clopidogrel is a thienopyridine prodrug. It must be oxidized by hepatic cytochrome P450 enzymes, chiefly CYP2C19, into an active thiol metabolite that irreversibly blocks the platelet P2Y12 ADP receptor. ADP acting on P2Y12 normally amplifies activation of GPIIb/IIIa, so blocking it reduces platelet aggregation, and with aspirin it forms dual antiplatelet therapy after stenting. Patients who carry two loss-of-function CYP2C19 alleles (poor metabolizers) generate little active drug, have higher on-treatment platelet reactivity, and have more stent thrombosis. Inhibitors of CYP2C19, such as omeprazole, have a similar but smaller effect. Ticagrelor (active without conversion and reversible) or prasugrel (little CYP2C19 dependence) are alternatives in such patients.

B. Acetylation of COX-1 is aspirin's action; aspirin is not a prodrug requiring CYP2C19, so this genotype does not affect it. C. Binding to GPIIb/IIIa describes the IV agents abciximab, eptifibatide and tirofiban, which he was not taking. D. PDE3 inhibition describes cilostazol, used for claudication. E. Impaired renal elimination would raise drug levels and cause bleeding rather than thrombosis, and it is unrelated to CYP2C19.

A patient with a prior NSAID ulcer who was switched to an anti-inflammatory drug that relieves arthritis pain without GI symptoms is taking celecoxib, a selective COX-2 inhibitor. Sparing COX-1 preserves gastric prostaglandins that maintain mucus, bicarbonate and mucosal blood flow, so ulcer risk falls.

The same selectivity explains the thrombotic risk. In vascular endothelium, COX-2 is a major source of prostacyclin (PGI2), which raises platelet cAMP, inhibits aggregation and causes vasodilation. Platelets express only COX-1, which makes thromboxane A2, a promoter of aggregation and vasoconstriction. Celecoxib lowers PGI2 but leaves platelet TXA2 untouched, tilting the balance toward thrombosis and increasing the risk of myocardial infarction and stroke, especially in patients with cardiovascular risk factors such as this one. It also has no antiplatelet effect of its own, and its sulfonamide group is a caution in sulfa allergy.

B. Irreversible acetylation of platelet COX-1 is aspirin's mechanism; it reduces thromboxane for the 7 to 10 day platelet lifespan and is antithrombotic, not prothrombotic.

C. Reduced antithrombin is a feature of nephrotic syndrome, liver disease and estrogen therapy, not COX inhibition.

D. Shunting of arachidonic acid to the lipoxygenase pathway explains aspirin-exacerbated respiratory disease (bronchospasm and nasal polyps), not coronary thrombosis.

E. Lipocortin (annexin A1) induction is how glucocorticoids inhibit phospholipase A2; celecoxib acts downstream at COX and does not inhibit lipocortin.

The drug is a neprilysin inhibitor (like sacubitril or the older agent candoxatril). Neprilysin is a membrane zinc metalloendopeptidase that degrades ANP, BNP, bradykinin and substance P, so blocking it raises natriuretic peptides, which act on particulate guanylate cyclase receptors to raise cGMP and cause natriuresis and vasodilation. The rise in urinary sodium and cGMP shows that this arm of the response is working.

However, neprilysin also breaks down angiotensin II. Inhibiting it alone therefore lets angiotensin II accumulate, and AT1 receptor mediated vasoconstriction, aldosterone release and sodium retention offset the natriuretic peptide benefit, leaving blood pressure nearly unchanged. Blocking the AT1 receptor with an ARB unmasks the vasodilator effect, which is why sacubitril is marketed only in combination with valsartan. An ACE inhibitor is not used as the partner because ACE and neprilysin both degrade bradykinin, and dual inhibition causes angioedema.

A. Downregulation of natriuretic peptide receptor A would blunt the cGMP response, but urinary cGMP rose. B. Faster clearance by natriuretic peptide receptor C would lower ANP, yet plasma ANP doubled. C. Natriuretic peptides do suppress renin release, but that would lower blood pressure further rather than oppose the drug. E. Neprilysin inhibition decreases, not increases, bradykinin degradation, and the resulting bradykinin excess is vasodilatory.

This man has carcinoid syndrome from a midgut (ileal) neuroendocrine tumor with hepatic metastases, and right-sided carcinoid heart disease (tricuspid regurgitation with large v waves and a pulsatile liver, plus pulmonic stenosis).

Serotonin from the primary tumor normally enters portal blood and is inactivated by hepatic monoamine oxidase on first pass, so a gut tumor alone rarely causes symptoms. Liver metastases drain directly into the hepatic veins and IVC, delivering serotonin, tachykinins and bradykinin to the right heart. Serotonin acting on 5-HT2B receptors stimulates myofibroblast proliferation, producing pearly-white plaques that thicken and fix the tricuspid and pulmonic leaflets. Blood then passes through the lungs, where pulmonary monoamine oxidase degrades serotonin to 5-HIAA, so the left heart is protected. Left-sided lesions appear only when serotonin bypasses the lungs: a PFO or ASD with right-to-left flow, a bronchial carcinoid draining into the pulmonary veins, or a very high hormone burden.

A. Hepatic first-pass metabolism explains why gut tumors without liver metastases spare the heart, but this patient's metastases bypass that barrier, so it cannot explain left-sided sparing.

B. Left-sided valves do express 5-HT2B receptors; fenfluramine and pergolide, which circulate freely, cause mitral and aortic regurgitation through them.

D. Pulmonary ACE does degrade bradykinin, but bradykinin causes flushing, not the fibrotic valve plaques, which are driven by serotonin.

E. Pressure does not prevent plaques; serotonergic drugs damage left-sided valves despite systemic pressures.