cardiology2016131140

cardiology2016 131-140,Q 1,This item has associated media that may require the use of headphones. Please ensure your system/speaker volume is set to an audible level.A 52-year-old man comes to the physician because of increasing fatigue over the last two weeks. He has also been experiencing exertional dyspnea and occasional headaches. Cardiac auscultation findings at the left sternal border are given below.Which of the following is most consistent with this patients auscultatory findings? A. Aortic regurgitation B. Hypertrophic cardiomyopathy C. Mitral valve prolapse D. Papillary muscle dysfunction E. Tricuspid regurgitation,A 1,Correct answer:AThe auscultatory findings in this patient are classic for aortic regurgitation, which is characterized by an early diastolic murmur. Although many patients with aortic regurgitation remain asymptomatic for decades, symptoms can occur as the regurgitant volume increases; including palpitations or atypical chest pain. Signs and symptoms of left heart failure can also occur, which may explain this patients exertional dyspnea and fatigue. The duration of the diastolic murmur can provide information about the severity of aortic regurgitation, with more advanced cases producing a holodiastolic murmur and mild cases leading to only an early diastolic murmur. In developed countries, aortic regurgitation is most commonly caused by aortic root dilation (in which the murmur is often best heard at the right sternal border) or a bicuspid aortic valve.(Choice B) Hypertrophic cardiomyopathy is almost always associated with mitral regurgitation secondary to impaired mitral valve closure, which would produce a systolic murmur as opposed to the diastolic murmur heard in this case.(Choice C) Mitral valve prolapse is classically associated with a midsystolic click and a late systolic murmur, not a diastolic murmur.(Choice D) Papillary muscle dysfunction can lead to mitral regurgitation; which, as stated above, would cause a systolic murmur.(Choice E) Similar to mitral regurgitation, tricuspid regurgitation would result in a systolic murmur as opposed to a diastolic murmur.Educational objective:Aortic regurgitation is characterized by an early diastolic murmur and is most commonly caused by aortic root dilation or a bicuspid aortic valve in developed countries.,Q 2,A 56-year-old man comes to the emergency department due to progressively worsening dyspnea. He can walk only a few blocks before becoming short of breath. He also finds it difficult to sleep lying flat and requires three pillows to prop himself upright when sleeping. The patient does not use tobacco, alcohol, or illicit drugs. His other medical problems include chronic hypertension, but he takes medication only when experiencing headaches. Blood pressure is 170/100 mm Hg and pulse is 80/min. Physical examination shows bilateral basilar lung crackles, jugular venous distension, and bilateral lower extremity edema. A chest x-ray reveals cardiomegaly and hilar prominence. An electrocardiogram (ECG) shows left ventricular hypertrophy. An echocardiogram shows pulmonary arterial hypertension. Which of the following is the most likely underlying mechanism for this patients pulmonary hypertension?A. Hypoxia-induced pulmonary vasoconstriction B. increased pulmonary artery flow volume C. Inflammatory pulmonary vascular disease D. Mechanical obstruction of the pulmonary arterial tree E. Obliteration of the pulmonary vascular bed F. Vasoconstriction due to pulmonary venous congestion,A 2,Correct answer:FThis patient has left-sided heart failure (orthopnea and crackles) most likely due to long-standing, poorly controlled hypertension. Hypertensive heart disease is the most common cause of left ventricular (LV) diastolic dysfunction. It is characterized by concentric LV hypertrophy and decreased LV diastolic compliance. As a result higher diastolic filling pressures are needed to maintain stroke volume and cardiac output. This increase in pressure is transmitted backward to the left atrium and pulmonary veins, where it can cause pulmonary hypertension (PH) and subsequent right-sided heart failure (jugular venous distension, prominent peripheral edema).The pathogenesis of PH due to left heart disease begins with a passive increase in pulmonary capillary and arterial pressure secondary to pulmonary venous congestion. The high pressures result in endothelial damage and capillary leakage of seaim proteins into the interstitium. This leads to decreased production of nitric oxide (vasodilator) and increased production of endothelin (vasoconstrictor) by the dysfunctional epithelium, resulting in increased vascular tone. Overtime, remodeling of the pulmonary vasculature occurs with increased smooth muscle cell proliferation (medial hypertrophy) and collagen and elastase deposition (intimal thickening and fibrosis). Remodeling is less extensive than in (idiopathic) pulmonary arterial hypertension; therefore. PH due to left heart disease is usually at least partially reversible following correction of the underlying abnormality (eg, LV dysfunction, mitral valve disease).(Choices A and E) Hypoxia-induced vasoconstriction and emphysematous obliteration of the vasculature underlie the pathogenesis of PH due to chronic obstructive pulmonary disease (COPD). This patients PH is more likely due to heart failure than to COPD.(Choice B) Congenital heart diseases that cause left-to-right shunts can increase pulmonary artery flow volume. A large ventricular septal defect will cause PH at a young age secondary to early pulmonary vascular remodeling. Atrial septal defects typically take longer to produce such effects due to a lesser degree of shunting and pressure overload. Although pulmonary artery pressures rise in the setting of left heart failure, pulmonary arterial flow will remain the same or decrease as heart failure worsens.(Choice C) Inflammatory pulmonary vascular disease can be seen in pulmonary vasculitides such as granulomatosis with polyangiitis (Wegeners) and eosinophilic granulomatosis with polyangiitis (Churg-Strauss). In rare instances, these can result in secondary PH.(Choice D) Mechanical obstruction of the pulmonary arterial tree occurs in acute pulmonary embolism. Some patients with pulmonary embolism develop chronic thromboembolic pulmonary hypertension despite receiving appropriate treatment. However, this patient has no history of thromboembolic pulmonary disease, and his orthopnea and crackles are more suggestive of PH due to left heart failure.Educational objective:Left-sided heart disease can cause pulmonary hypertension by increasing pulmonary venous pressure and congestion. This leads to a passive increase in pulmonary arterial pressure, which is made worse by reactive vasoconstriction and structural remodeling of the pulmonary vasculature secondary to impaired nitric oxide availability and increased endothelin expression.,Q 3,A 50-year-old male begins treatment with an antiarrhythmic medication for recurrent atrial fibrillation. The arrhythmia resolves, and there is now mild bradycardia and significant QT interval prolongation on his EKG recording. Which of the following drugs was most likely used in this patient?A. Metoprolol B. Propranolol C. Sotalol D. Carvedilol E. Verapamil F. Diltiazem,A 3,Correct answer:CThe QT-interval represents the period of ventricular repolarization as the ventricles prepare for the next beat. Repolarization is mediated by K+ efflux from the cardiac myocyte. Sotalol is a beta-blocker with class 3 (K- channel blocking) antiarrhythmic properties. Other class 3 antiarrhythmics include amiodarone, ibutilide. and dofetilide. Sotalol is the only class 3 antiarrhythmic with beta-adrenergic blocking abilities (causing the patients mild bradycardia) as well as class 3 effects (causing the QT interval prolongation).Choices A, B, and D) Metoprolol, propranolol and carvedilol are beta-blockers like sotalol, but these medications lack sotalols class 3 K* blocking effects. Beta-blockers decrease heart rate and cardiac contractility by slowing AV nodal conduction and the phase 4 depolarization of cardiac pacemaker cells. They are useful as rate controlling agents, as myocardium protective agents following myocardial infarction or in CHF resulting from systolic dysfunction, and as antihypertensives. They do not prolong the QT interval.(Choices E and F) Verapamil and diltiazem are calcium channel blockers that affect cardiac tissue and are therefore class 4 antiarrhythmic agents. Verapamil is the most cardioselective, but both will act on the peripheral vasculature as well, causing a decrease in blood pressure. As calcium channel blockers, these medications slow the phase 0 depolarization of cardiac pacemaker cells and phase 2 of the myocyte action potential, neither of which will change the QT interval. Their adverse effects include negative inotropy and the potential for AV block. Verapamil is additionally associated with gingival hyperplasia and constipation.Educational Objective:Sotalol has both beta-adrenergic blocking properties and class 3 antiarrhythmic (K-channel blocking) properties. It prolongs both the PR interval and the QT interval.,Q 4,A 45-year-old male with atrial fibrillation receives dofetilide as a means of pharmacologic cardioversion and the arrhythmia resolves This medication exerts its main effect on which portion of the action potential curve?A.A B.B C.C D.D E.E,A 4,Correct answer:EThe action potential pictured above is that of a cardiac myocyte with phases 0(B), 1(C), 2(D), 3(E) and 4(A). Remember that this differs from the action potential of cardiac pacemaker cells which have only phases 4, 0 and 3. Dofetilide is a class 3 (K+ blocking) antiarrhythmic agent that slows potassium efflux from the cardiac myocyte. Thus, it mainly affects phase 3 (Choice E).(Choice A) Phase 4 of the myocyte action potential is the resting portion of the curve where ingoing and outgoing currents are balanced.(Choice B) During phase 0 of the cardiac myocyte action potential, there is a large influx of sodium ions into the cell that causes the cell to depolarize. The class I antiarrhythmics alter phase 0 of the action potential by modulating the sodium permeability of the cell membrane.(Choice C) Phase 1 of the action potential is a brief period of cell membrane repolarization mediated by a sharp decrease in sodium conductance and an increase in potassium permeability. It is not modulated to an appreciable extent by antiarrhythmic medications.(Choice D) Phase 2 of the cardiac myocyte action potential is the plateau of theaction potential where movement of ions into (Ca) and out of (K+) the cell isrelatively equal. K+-blocking agents (class 3 antiarrhythmics) do modulate this portion of the action potential, but exert their greatest effect during phase 3, which is completely dependent on potassium efflux. The antiarrhythmic effect of the calcium channel blockers applies only to calcium sensitive tissues of the heart such as the AV node.Educational Objective:Class 3 antiarrhythmic agents block potassium efflux from cardiac myocytes and prolong phase 3 of the myocyte action potential.,Q 5,A 53-year-old man with a known history of hypertension comes to the emergency department with shortness of breath and chest tightness. The patient was playing in a poker tournament when his symptoms first began. He has a history of hypertension and is not compliant with his medications. His last medical follow-up was a year ago. Blood pressure is 195/115 mm Hg and pulse is 90/min and regular. Lung examination reveals bibasilar crackles. Nitroglycerin infusion is started and results in significant symptomatic improvement. Repeat blood pressure is 165/90 mm Hg. Which of the following intracellular events is most likely responsible for the beneficial effects of this patients treatment?A. Actin phosphorylation B. Calcium release from sarcoplasmic reticulum C. Enhanced cyclic mononucleotide degradation D. Inositol triphosphate accumulation E. Myosin dephosphorylation F. Tyrosine kinase activation,A 5,Correct answer: EThis patients clinical presentation is consistent with acute pulmonary edema due to severely elevated blood pressure (hypertensive emergency). In such cases, intravenous vasodilators (nitroglycerine, sodium nitroprusside) are often used to improve the acute heart failure by reducing afterioad.Nitrates are metabolized within vascular smooth muscle cells to nitric oxide, which activates guanylate cyclase and promotes the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). Increased levels of cGMP lead to decreased intracellular calcium, resultant decreased activity of myosin light-chain kinase, and, finally, myosin light chain dephosphorylation and vascular smooth muscle relaxation.(Choice A) Actin phosphorylation has no role in smooth or skeletal muscle relaxation. In smooth muscle, a stimulus to contract leads to increased intracellular calcium, which leads to myosin phosphorylation. Once myosin is phosphorylated, it is able to bind directly to actin and cause muscle contraction.(Choice B) Calcium release from sarcoplasmic reticulum would lead to increased contraction of the cardiac myocytes. It is not involved in the mechanism of action of nitrates on vascular smooth muscle cells.(Choice C) Nitrates do not cause an increase in cyclic mononucleotide degradation. On the contrary, they activate guanylate cyclase and promote conversion of GTP to cGMP. which ultimately leads to smooth muscle relaxation(Choice D) Inositol triphosphate binds to its receptor on the endoplasmic reticulum and leads to the release of Ca：- into the cytoplasm. In vascular smooth muscle cells, this increased concentration of cytoplasmic Ca7* results in increased smooth muscle contraction.(Choice F) Tyrosine kinases play a role in a wide variety of intracellular processes and pathways. The effects of insulin and insulin-like growth factor occur via activation of receptor tyrosine kinases, which in turn cause phosphorylation of tyrosine residues on intracellular proteins important for signal transduction.Educational objective:Nitrates (via conversion to nitric oxide) activate guanylate cyclase and increase the intracellular levels of cyclic guanosine monophosphate (cGMP). Increased levels of cGMP lead to decreased activity of myosin light-chain kinase and myosin light chain dephosphorylation, resulting in vascular smooth muscle relaxation.,Q 6,Milrinone is a strong inotropic agent. Its mechanism of action involves inhibition of phosphodiesterase isoenzyme 3. Which of the following additional responses is most likely an extension of its pharmacologic effect?A. Angioedema B. Antiarrhythmic action C. Vasodilation D Increased right atnal pressure E. Sodium and water retention F. AV conduction block,A 6,Correct answer: CMilrinone, as stated in the question stem, is a phosphodiesterase isoenzyme 3 inhibitor. In the cardiac myocyte phosphodiesterase isoenzyme 3 acts to metabolize cyclic AMP (cAMP), an important second messenger in excitation-contraction coupling. cAMP is formed from ATP by adenylyl cyclase, the activity of which is stimulated by beta agonists. Cyclic AMP increases the conductance of the calcium channels in the sarcoplasmic reticulum, and as a result, more calcium can enter the cell and strengthen the force of contraction. Thus, the inhibition of phosphodiesterase isoenzyme 3 by milrinone can increase cardiac contractility.In vascular smooth muscle, increases in cAMP cause vasodilation, a well-known side effect of phosphodiesterase inhibitors which can occasionally limit their use in hypotensive patients.(Choice A) Angioedema is most frequently manifest as rapid-onset swelling of the lips and larynx. It is a serious, though rare, side effect of ACE-inhibitors.(Choice B) Antiarrhythmic medications are broken into 6 classes based on their mechanism of action (class IA, IB, and IC drugs modulate sodium channels; class II drugs act on the sympathetic nervous system; class III drugs modulate potassium channels; class IV drugs are calcium channel blockers). Phosphodiesterase inhibitors do not have antiarrhythmic properties.(Choice D) A strong inotropic agent, which milrinone was identified as in the question stem, would not cause increased right atrial pressure.(Choice E) Sodium and water retention would not be a desired effect in a patient with congestive heart failure and is not an effect of the phosphodiesterase inhibitors.(Choice F) AV Conduction block can be caused by digitalis toxicity, but it is not an effect of the phosphodiesterase inhibitors.Educational Objective:Phosphodiesterase inhibitors lead to increased cardiac contractility via increased intracellular cAMP concentration. cAMP promotes increased intracellular calcium in cardiac myocytes and is normally metabolized by phosphodiesterases. In vascular smooth muscle, increases in cAMP cause vasodilation, a well-known side effect of phosphodiesterase inhibitors which can occasionally limit their use in hypotensive patients.,Q 7,A 64-year-old man with stable angina is being treated with atenolol and aspirin. He reports that over the last week, his symptoms have been worsening. His physician decides to add a new medication to his regimen. Several days later, he presents to the emergency room complaining of severe dizziness. On physical examination, his blood pressure is 100/70 mm Hg and his heart rate is 38 beats per minute. Which of the following medications was most likely administered?A. Nifedipine B. Captopril C. Verapamil D Isosorbide dinitrate E. Prazosin,A 7,Correct answer:CMedications with negative chronotropic effects |-adrenergic blockers (eg, metoprolol, atenolol)Non-dihydropyridine calcium channel blockers (eg. verapamil, diltiazem)Cardiac glycosides (eg. digoxin)Amiodarone and sotalolCholinergic agonists (eg, pilocarpine, rivastigmine)-adrenergic blocking agents are frequently used in patients with stable angina pectoris in order to reduce myocardial oxygen demand and improve symptoms. They are usually titrated to achieve a target heart rate of 55 to 60 beats per minute. This patients heart rate is significantly lower, indicating that the new drug has a negative chronotropic effectWhen used concomitantly, non-dihydropyridine-type calcium channel blockers (eg, ve