cardiovascular physiology - cardiac cycle and murmurs

Cardiovascular Physiology

• Describe what is happening at each point of the following curve?

• The graph above depicts the left ventricular pressure and volume during the cardiac cycle. Together these graphs can be used to plot the various phases of the cardiac cycle. First, on the left, is atrial systole. In this phase, blood is forcefully expelled from the atria into the ventricles causing the slight increase in ventricular pressure and volume seen on the far left of the graph.

• Next the mitral valve closes causing a slight depression of the ventricular pressure curve (marked as point A above). The ventricle then begins to contract. The segment between points A and B corresponds to isovolumetric contraction. During this time the ventricular pressure increases but the ventricular volume remains the same because the aortic and mitral valves are closed.

• When the ventricular pressure exceeds the diastolic systemic blood pressure the aortic valve opens (point B). Now the ventricular volume begins to decrease sharply as blood is expelled. The left ventricular pressure continues to increase between points B and C until the systolic maximum blood pressure is reached.

• When these two values are equal, the aortic valve closes (point C). Isovolumetric relaxation occurs between points C and D. The ventricle relaxes and both the aortic and mitral valves are closed. At point D, the mitral valve opens, initiating the phase of diastolic filling.

Which of the following causes the changes depicted by the following curves?a) Excessive hydration b) Acute hemorrhage c) Chronic anemia d) Myocardial infarction e) Anaphylaxis

• The graph above combines cardiac and vascular function curves. The cardiac function curve, labeled as cardiac output (CO) illustrates the Frank-Starling effect. • The Frank-Starling effect states that as cardiac muscle is increasingly

stretched, the cardiac output increases (up to a limit). This is essentially a length-tension relationship. This relationship reaches its limit at the flat portion of the curve. • The vascular function curve, labeled venous return, gives the mean systemic

pressure where it intersects with the x axis and the total peripheral resistance (TPR) with its slope. Increases in blood volume shift this graph to the right and increases in the TPR decrease the slope of the curve (in part due to the increased afterload in the systemic circulation).

• The dashed lines depict decreased cardiac output and unchanged venous return (unchanged blood volume and TPR). An isolated decrease in cardiac output indicates decreased contractility that is not the result of decreased preload (because the venous return line is unchanged). This indicates either the action of a negative inotropic drug or injury to the myocardium inhibiting contraction, such as a myocardial infarction.

• (Choice A) Excessive hydration or a blood transfusion would increase the blood volume; shift the venous return graph to the right and change the cardiac output from point A to point B. Because there is more volume in the right atrium, the right atrial pressure is also elevated. • (Choice B) Acute hemorrhage would cause a sharp decrease in the circulating

blood volume and would shift the venous return curve to the left. • (Choice C) Chronic anemia causes an increase in cardiac output in an effort to

meet the metabolic demands of the tissues. This causes an increase in the slope of the cardiac output graph. • (Choice E) Anaphylaxis causes widespread venous and arteriolar dilatation along

with increased capillary permeability and third-spacing of fluids. This results in a serious drop in venous return.

Which of the following is most likely to increase as a result of the change shown by the dashed line?a) Ventricular Preloadb) End-diastolic pressurec) Ventricular afterloadd) End-systolic volumee) Ejection fraction

• The ventricular pressure-volume loop depicts the relationship between pressure and volume in the left ventricle during systole and diastole. Left ventricular contraction ejection, relaxation and refilling are represented as follows:

• The dashed loop reflects an increase in cardiac contractility and stroke volume as evidenced by the increased ejection volume and higher systolic pressure generated.

• Increased ventricular preload would be represented by widening of the ventricular pressure-volume loop to the right, corresponding to an increased intra ventricular volume during diastolic filling. End-diastolic pressure would be increased by an increased preload.

• Ventricular afterload is increased when there is increased systemic blood pressure against which the ventricle must pump. The ventricular pressure-volume loop would show elevated pressures during the isovolumetric ventricular contraction phase before the aortic valve opens.

• End-systolic volume would be increased in states of decreased cardiac contractility: the ventricular pressure-volume loop would be narrowed by shifting the isovolumetric relaxation line to the right.

If an arteriovenous shunt is created by a particular injury, what would most likely result in which of the following changes of the left ventricular pressure-volume loop?

If an arteriovenous shunt is created by a particular injury, what would most likely result in which of the following changes of the left ventricular pressure-volume loop? Answer = B

• Arteriovenous (AV) shunts result from the formation of AV fistulas. An AV fistula is an abnormal communication between an artery and a vein that bypasses the capillary beds, which are the major source of resistance in the vascular system. Thus AV shunts allow blood under arterial pressure to directly enter the venous system. AV fistulas can be congenital or acquired (e.g. secondary to penetrating injuries or iatrogenically created for the purpose of dialysis access). In patients with an AV fistula, physical exam will reveal a pulsatile mass with a thrill on palpation.

• Auscultation reveals a constant bruit over the site. • Pressure-volume loops represent the relationship between pressure and volume in

the left ventricle during systole and diastole. AV shunts increase cardiac preload by increasing the rate and volume of blood flow back to the heart. This increase in the diastolic ventricular volume causes elongation of the diastolic filling segment (bottom line) on the ventricular pressure-volume loop. Loop B reflects these changes.

• (Choice A) This graph represents an increase in cardiac contractility. Increased contractility generates higher systolic blood pressures and causes an increased volume of blood to be ejected from the ventricles as compared to baseline. • (Choice C) This graph represents increased afterload. Afterload is the

pressure against which the heart must pump to force blood into the systemic circulation. The loop is taller because elevated pressures are required in this state, and it is narrower because the ventricle cannot eject as much volume in the face of an increased afterload. Thus stroke volume is decreased. • (Choice D) This graph represents decreased preload.

Which of the following pairs of pre-medication (solid curve) and post-medication (dashed curve) left ventricular pressure/volume relationships best represents the effects of nitroprusside in this patient?

Which of the following pairs of pre-medication (solid curve) and post-medication (dashed curve) left ventricular pressure/volume relationships best represents the effects of nitroprusside in this patient? Answer = E

• Nitroprusside is a short-acting balanced venous and arterial vasodilator. As such it decreases left ventricular (LV) preload and afterload, allowing an adequate cardiac output to be delivered at a lower LV end diastolic pressure (LVEDP). Of the choices given, only graph E shows a decrease in both LVEDP (preload) and mean systolic intraventricular pressure (afterload) without a reduction in stroke volume.

• (Choice A) Here the preload is unchanged. The dashed LV pressure/volume curve reflects an increase in cardiac contractility. Nitroprusside decreases preload and afterload but does not directly alter cardiac contractility. • (Choice B) Here the preload is increased. • (Choice C) Here both the preload and afterload have increased, while

the end systolic volume and stroke volume have decreased. • (Choice D) While this graph appropriately depicts decreased preload,

nitroprusside infusion would also reduce afterload to maintain adequate cardiac output.

Describe the phases depicted by the following diagram

• This pressure-volume loop depicts the relationship between pressure and volume in the left ventricle during systole and diastole. Left ventricular contraction ejection, relaxation and refilling are shown as follows:

• 1. Isovolumetric contraction: This phase of the cardiac cycle begins with the closure of the mitral valve at point

• A. During this period of time the left ventricle is contracting and intraventricular pressure is increasing, but no blood is leaving the ventricle because both the aortic and mitral valves are closed. The pressure in the left ventricle continues to increase until the systemic diastolic blood pressure is reached and the aortic valve opens at point B.

• Ventricular ejection: This phase of the cardiac cycle is represented by the curved line between points B and Con the graph. This phase begins with the opening of the aortic valve at point B and represents the period of time where blood is actively squeezed out of the ventricle and into the systemic circulation.

• Isovolumetric relaxation: This phase of the cardiac cycle is represented by the line between points C and D on the above graph. This phase begins with closure of the aortic valve at point C. The pressure in the ventricle decreases during this time, but no blood enters or leaves the ventricle because both the aortic and mitral valves are closed.

• Ventricular filling: This phase is represented by the line between points D and A on the above graph. This phase begins with the opening of the mitral valve at point D, and during this time blood fills the ventricles.

• The patient described above most likely has mitral stenosis. The “opening snap” results from the abrupt halting of motion of the stenotic mitral valve leaflets during mitral valve opening. Mitral valve opening is represented by point D on the above graph. The diastolic rumbling murmur is the result of turbulent blood flow through the stenotic mitral valve during left atrial contraction. Prior rheumatic carditis is the most common cause of mitral stenosis.

A 43-year-old man is rushed to the emergency room following repeated episodes of coffee ground-appearing emesis. He has a blood pressure of 70/40 mmHg, a heart rate of 130/mm, and his extremities are cool to the touch. Immediate infusion of 2L of normal saline is expected to increase: a) Total peripheral resistance b) Ventricular muscle contraction velocity c) End-diastolic sarcomere length d) Heart rate e) Diastolic ventricular compliance

• This patient is most likely experiencing a brisk upper gastrointestinal bleed. ‘Coffee ground emesis suggests the presence of blood in the vomitus that has been exposed to gastric acid. The coffee ground color of the blood is caused by the oxidation of heme iron.

• The patient’s clinical presentation indicates that he has lost a considerable amount of blood and is experiencing hypovolemic shock. The human body can sustain a normal blood pressure and cardiac output with blood losses of up to 10% of the circulating blood volume. After this point the sympathetic nervous system is activated leading to constriction of the arteriolar and venous beds as well as stimulation of the heart.

• Constriction of the arteriolar beds serves to increase total peripheral resistance and maintain end organ pressure. It also serves to shunt blood away from the extremities and skin and toward the vital organs (hence the patient’s cool extremities). Constriction of the venous circulation increases blood return to the heart, thereby assisting in maintaining preload.

• Finally, stimulation of the heart results in increased contractility and heart rate. Despite these actions of the sympathetic system, progressive bleeding will lead to a drop in blood pressure. • In the treatment of hypovolemic shock the most important intervention other than

identifying and eliminating the source of bleeding is rapid infusion of blood products and crystalloid solutions like normal saline. In a patient with hypovolemic shock the intravascular volume is low and the sympathetic system is maximally stimulated thus administration of vasopressors is of little benefit beyond a small temporary effect in some cases. • By infusing intravenous fluids one can immediately increase the intravascular

volume and ventricular preload. The preload increase extends the end diastolic sarcomere length in the ventricular myocardium increasing stroke volume and cardiac output.

• (Choices A and B) In a patient with hypovolemic shock total peripheral resistance and contraction velocity are high due to sympathetic activation. Administration of fluids will reduce sympathetic activation and decrease both of these parameters. • (Choice D) Fluid resuscitation of the hypovolemic patient will cause the

heart rate to decrease. • (Choice E) The diastolic ventricular compliance is unaffected by crystalloid

infusions. Compliance is affected by pathologic processes acting on the heart itself such as amyloid cardiomyopathy and hypertrophic cardiomyopathy two processes that decrease compliance. Dilated cardiomyopathies increase ventricular compliance.

Murmurs

A 38 year old female is being evaluated for progressive exertional dyspnea. The cardiac catheterization data are obtained. Left ventricular end-diastolic pressure – 10 mmHg (normal 3 -12 mmHg). Left ventricular peak systolic pressure – 110 mmHg (normal 100 -140 mmHg), Pulmonary capillary wedge pressure – 36 mmHg (normal <12mmHg). Which of the following is the most likely cause of this patient’s symptoms?a) Mitral stenosis b) Aortic stenosis c) Dilated cardiomyopathy d) Restrictive cardiomyopathy e) Cardiac tamponade

• The pulmonary capillary wedge pressure (PCWP) is the pressure in a pulmonary artery distal to the point of its occlusion by an inflated intravascular balloon. • Because there is no significant blood flow towards the left atrium (LA)

beyond this point of occlusion, the pressure at the tip of the “wedged” pulmonary artery catheter becomes nearly equal to the LA pressure. • During normal diastole, the LA pressure is nearly equal to the left ventricular

(LV) pressure since the open mitral valve offers minimal resistance to flow between the two chambers. In this patient, cardiac catheterization reveals a LA end-diastolic pressure (LAEDP) that is significantly greater than the LVEDP. This abnormal pressure gradient implies increased resistance flow between the LA and LV, i.e. mitral stenosis.

• (Choice B) Isolated aortic stenosis would cause elevation of the left ventricular peak systolic pressure. It could also elevate both the PCVVP and the LVEDPI but these two values would remain approximately equal. • (Choice C) Dilated cardiomyopathy would reduce the left ventricular peak

systolic pressure and elevate the PCWP and LVEDP. The PCWP and LVEDP would remain approximately equal. • (Choice D) Restrictive cardiomyopathy causes diastolic dysfunction and

similar elevations of the PCVVP and LVEDP. The PCWP and LVEDP would remain approximately equal. • (Choice E) In the absence of mitral stenosis, tamponade would elevate the

PCWP and LVEDP to the same degree, keeping them equal.

A 53-year-old male presents to your office with difficulty breathing and increasing fatigue. He has been sleeping in a recliner chair to relieve his shortness of breath. His past medical history is significant for a myocardial infarction two months ago. On cardiac auscultation, a diastolic sound is heard when the patient lies in the left lateral decubitus position. Which of the following is most likely to accentuate this physical examination finding? a) Valsalva maneuver b) Expiration c) Standing d) Furosemide injection e) Amyl nitrite inhalation

• This patient presents with signs and symptoms of heart failure. Heart failure can result from a variety of pathogenic processes. Repeated bouts of myocardial ischemia are the most common cause.

• In heart failure resulting from systolic dysfunction the ejection fraction is decreased and the heart is left with a considerable end-systolic volume within the ventricles. An 53, or ventricular gallop heart sound is commonly heard in patients with left ventricular failure (this can be a normal variant in healthy children and adolescents). The 33 heart sound is a low frequency sound that occurs immediately following 32 during the phase of rapid passive ventricular filling. It results from blood rushing into a partially filled ventricle or into a very stiff ventricle in patients with restrictive cardiomyopathy.

• The 33 is best appreciated with the bell of the stethoscope pressed lightly against the skin in the region of the ventricular apex. (The bell is well-suited to detect low frequency sounds while the diaphragm is best for hearing high-pitched sounds like S1 and S2.) Having the patient lie in the left lateral decubitus position makes it easier to hear 53. Having the patient exhale completely while in this position can make the sound even more audible by decreasing the volume of the lungs and bringing the heart closer to the chest wall.

• (Choices A and C) The Valsalva maneuver (bearing down against a closed glottis) and the standing position can be used to differentiate between the various causes of a systolic murmur in the left heart. Both maneuvers decrease venous return to the heart thereby reducing left ventricular volume and blood pressure. The murmurs associated with mitral valve prolapse and hypertrophic cardiomyopathy become more audible and those associated with aortic stenosis become less audible. Squatting and Valsalva release (maneuvers that increase venous return) have the opposite effect.

• (Choice D) Furosemide injection causes brisk diuresis. The volume reduction would likely lessen the intensity of the 33 sound.

• (Choice E) Amyl nitrite inhalation causes vasodilatation and decreased blood pressure. It would have the same effect as the Valsalva maneuver on the murmurs of mitral prolapse hypertrophic cardiomyopathy and aortic stenosis.

A 46 year old patient is referred to the cardiology department after a primary care physician hears a murmur on cardiac auscultation. Physical examination reveals bounding femoral pulses and carotid pulsations that are accompanied by head-bobbing. This patient most likely suffers from:a) Mitral stenosisb) Aortic stenosisc) Tricuspid Regurgitationd) Mitral Regurgitatione) Aortic Regurgitationf) Pulmonary Stenosis

• This patient’s physical exam findings are classic for aortic regurgitation (AR). In patients with AR, there is a large left ventricular stroke volume (LVSV) a large regurgitant SV, and a large pulse pressure. The left ventricular end diastolic volume is also increased due to the incompetent aortic valve. Bounding femoral and carotid pulses marked by abrupt distention and quick collapse (“water-hammer” pulses) are the result of the large pulse pressure. Some patients exhibit head-bobbing with carotid pulsations (de Musset sign) due to transfer of momentum from the large left ventricular stroke volume (LVSV) to the head and neck.

• (Choice A) In isolated mitral stenosis (MS), left ventricular diastolic pressures are usually near-normal. though pressures proximal to the stenotic mitral valve are typically elevated. Since the left ventricular end-diastolic volume is not elevated, stroke volume and pulse pressures are usually near-normal. • (Choice B) Aortic stenosis causes delayed, prolonged carotid pulses (pulsus

parvus et tardus). Systolic vibrations or a carotid “shudder” (thrill) may also be present. (Choices C and F) Neither tricuspid regurgitation nor pulmonary stenosis causes the pattern of physical findings described above. • (Choice D) Mitral regurgitation increases the LVSV but does not increase the

volume of blood ejected into the aorta. This patient’s physical examination findings are the result of an abnormally large volume of blood being ejected into the aorta.

A thrombus originating in the deep veins of the lower extremities is most likely to cause a stroke in a patient with which of the following physical findings? a) Splitting of S1 that is accentuated on inspiration b) Ejection-type systolic murmur that increases on standing c) Diastolic decrescendo-type murmur that decreases following amyl

nitrite inhalation d) Presystolic murmur that disappears with atrial fibrillation e) Splitting of S2 that does not change with respiration

• A patent connection between the right and left atria is a defect that would make a paradoxical embolism possible. Paradoxical emboli originate in the venous system, but cross over into the arterial circulation (bypassing the lungs) via an abnormal connection between the right and left heart. Wide splitting of S2 that does not vary with respiration can result from an atrial septal defect (ASD) a defect that would permit a paradoxical embolism.

• (Choice A) Assuming the patient had no S4 gallops or aortic ejection click, a split S1 accentuated on inspiration would indicate delayed closure of the tricuspid valve. This could be caused by a right bundle branch block and need not indicate any abnormal connection between the right and left cardiac chambers.

• (Choice B) A systolic ejection murmur (SEM) generally refers to a mid-systolic crescendo-decrescendo murmur, most commonly the result of aortic stenosis. Hypertrophic obstructive cardiomyopathy may also cause SEM. When in the upright position, venous return to the heart is decreased and the left ventricular enddiastolic volume and stroke volume are reduced, increasing the SEM of hypertrophic obstructive cardiomyopathy. Neither of these lesions by themselves would permit a paradoxical embolus.

• (Choice C) An early diastolic decrescendo murmur is characteristic of aortic regurgitation (AR). Inhaled amyl nitrite produces marked vasodilatation, resulting in reduction of systemic arterial pressure and decreasing this regurgitant murmur. Isolated AR does not result in an abnormal right-to-left heart connection that would permit paradoxical embolism. • (Choice D) “Presystolic accentuation” occurs when the intensity of a diastolic

murmur becomes louder just prior to S1 or when a diastolic murmur appears just prior to S1. A presystolic (late diastolic) murmur can result from mitral or tricuspid valve stenosis and/or physiologically increased blood flow across these valves. Presystolic accentuation occurs due to atrial contraction. Atrial fibrillation could eliminate an atrioventricular valve stenotic murmur by removing the atrial contraction during late diastole. However, tricuspid and/or mitral stenosis alone would not permit a paradoxical embolus.

A 73-year-old Caucasian male presents to your office following repeated episodes of exertional dyspnea. Physical examination reveals a cardiac murmur. The patient is referred to cardiologist or further evaluation. Cardiac catheterization is performed and the findings are shown on the slide below. Which of the time points indicated on the slide best corresponds to the peak of the murmur intensity in this patient? a) Ab) Bc) Cd) De) Ef) F

• The hemodynamic profile shows an abnormal pressure gradient between the left ventricle (LV) and the aorta (Ac) during systole (see arrows in graph below), indicating significant aortic stenosis (AS).

• The intensity of the murmur of AS is directly related to the magnitude of the LV-toaorta pressure gradient. Thus the murmur in this patient would be loudest at point B and less intense at point A. • (Choices A and C) The murmur of AS is a systolic ejection-type

crescendodecrescendo murmur that starts after the first heart sound, following the opening of the aortic valve (time A). It typically ends before the A2 component of the second heart sound (time C). At times A and C, the left ventricular and aortic pressures are nearly equal so that a murmur due to flow across the aortic valve would be unlikely at these points.

• (Choices D and E) These points occur during diastole, when the aortic valve is closed and the mitral valve is open. There is no abnormally elevated pressure gradient between the left atrium and left ventricle, consistent with normal unobstructed diastolic filling of the left ventricle. Since turbulent flow due to a high pressure gradient is generally required to produce a murmur the patient would not have a murmur at times D or E. • (Choice F) This time point corresponds to atrial contraction just prior

to ventricular systole. There is no abnormally elevated pressure gradient between the left atrium and left ventricle consistent with normal unobstructed filling of the left ventricle.

A 52-year-old Caucasian male presents to your office for a routine checkup. He says that ‘some cardiac problems were detected during his previous visit to the doctor. Physical examination reveals a holosystolic murmur at the apex that radiates to the axilla. Which of the following is the best indicator of the severity of this patient’s problem? a) Holosystolic murmur intensity b) Presystolic component of the murmur c) S2 to opening snap (OS) time interval d) Presence of audible S3 e) Presence of audible S4

• Under most modern clinical circumstances, the anatomy and severity of mitral regurgitation (MR) are best delineated by2D and Doppler echocardiography. Among auscultator findings, the best indicator of a high regurgitant volume indicating severe MR with left ventricular volume overload is the presence of a left ventricular S3 gallop. A left ventricular (LV) S3 gallop reflects an increased rate of filling of the LV during mid diastole. It can be heard as a consequence of MR and in this condition reflects the relatively high volume of regurgitant flow which is “recycled” back into the LV during diastole.

• (Choice A) If the volume of left ventricular blood pumped backed into the left atrium during systole, or regurgitant volume, is used as a measure of severity of mitral regurgitation (MR), then one might expect the murmur of MR to become louder as regurgitant volume increased. However, this would only apply to an anatomically fixed effective regurgitant orifice (ERO). In the clinical setting, patients with higher regurgitant volumes may also have larger EROs, such that systolic transvalvular flow resistance and the degree of turbulence in the regurgitant jet (which accounts for the intensity of the murmur of MR) may not be strongly correlated with regurgitant volume.

• (Choice B) The murmur of mitral regurgitation is either holosystolic or, in some cases of mitral valve prolapse, midsystolic. In some cases of severe MR, a diastolic rumble produced by a high rate of flow across a normal sized diastolic mitral orifice may be heard. The latter amounts to a functional murmur (relative mitral stenosis) but is a less reliable finding with a high regurgitant volume than is the presence of an S3. (Choice C) The S2 to opening snap interval is a diastolic interval between the second heart sound (specifically A2) and the tensing of a stenotic mitral valve. It is a parameter of mitral stenosis, not mitral regurgitation.

• (Choice E) In a patient with mitral regurgitation, a left ventricular S4 gallop would most likely be a sign of left heart failure, indicating LV dilatation and the reaching of the limit of LV compliance during end diastole. However, many patients with severe MR have not yet developed left sided heart failure. In the latter group of patients, a left sided S3 would be a more likely finding on cardiac auscultation than a left sided S4.

A 32-year-old Asian female presents to your office complaining of easy fatigability and exertional dyspnea. Cardiac auscultation reveals an extra diastolic sound and a diastolic murmur at the apex. You suspect mitral stenosis. Cardiac catheterization findings are given on the slide below. Which of the following corresponds to the opening snap (OS) timing in this patient? a) Ab) Bc) Cd) De) E

• The opening snap (OS) in patents with mitral stenosis is an early diastolic sound due to tensing of the abnormal mitral valve (MV) leaflets after the valve cusps have completed their opening excursion. This occurs shortly after the mitral valve opens, when left ventricular pressure drops below left atrial pressure.• From the graph above, it can be seen that the higher the early diastolic

left atrial pressure the closer the opening snap will tend to be to point B, which corresponds to the A2 component of the heart sound. • The A2-OS interval is inversely correlated with the severity of mitral

stenosis. The more severe the stenosis, the higher the steady state left atrial pressure in early diastole and the shorter the A2-OS interval

• (Choice A) This point corresponds to the opening of the aortic valve at the end of isovolumetric ventricular contraction in early systole, when the left ventricular pressure exceeds the aortic pressure.

• (Choice B) Point B corresponds to the closure of the aortic valve at the end of systole, producing the A2 component of the second heart sound. The aortic valve closes as soon as left ventricular pressure drops below the aortic pressure.

• (Choice D) This is a random point in diastole, when the mitral valve is already maximally open and ventricular filling is progressing. Note that there is a significant gradient of pressure between the left atrium and left ventricle during diastole, consistent with mitral stenosis. Under normal conditions, diastolic left atrial and left ventricular pressures are nearly equal.

• (Choice E) Point E roughly corresponds to the onset of atrial contraction during late ventricular diastole. The mitral valve is still maximally open. Note the increase in the gradient of pressure between the left atrium and left ventricle produced by atrial contraction. This can cause presystolic accentuation of the diastolic murmur of mitral stenosis.

A 12-year-old Caucasian male is found to have a wide, fixed splitting of the second heart sound (S2) on routine physical examination. He denies any symptoms. If present, the congenital heart disease in this patient may require surgical repair to prevent irreversible changes in the: a) Right ventricle b) Right atrium c) Left ventricle d) Left atrium e) Pulmonary vessels f) Coronary vessels

• Wide fixed splitting of S2 that does not vary with respiration is a characteristic auscultatory finding of an atrial septal defect (ASD). ASD creates a left-to-right shunt because of the high pressure in the left atrium. The result is increased blood flow through the pulmonary artery.

• The muscular pulmonary arteries may develop laminated medial hypertrophy that can become so severe overtime as to increase the pulmonary vascular resistance above the total systemic vascular resistance. At this point the original left-to-right intracardiac shunt reverses, and flow becomes right-to- left.

• This switch to right-to-left shunting manifests as late-onset cyanosis, with clubbing and polycythemia. Eisenmenger syndrome is the name for reversal of shunt flow through a congenital cardiac defect that occurs as a result of chronic pulmonary hypertension. Overtime the pulmonary vascular sclerosis becomes irreversible and closure of the cardiac septal defect can no longer be hemodynamically tolerated by the right ventricle.

• (Choices A and B) Pulmonary hypertension produced by an ASD could result in right ventricular hypertrophy and right atrial enlargement. However, these changes are not necessarily irreversible. If the pulmonary hypertension is corrected, the right heart can revert to a more normal morphology. • (Choices C and D) Left ventricular failure is uncommon in patients

with ASD. Left atrial enlargement can be present due to volume overload but the main changes are in the right side of the heart.

A 72-year-old Caucasian male has a presystolic sound on cardiac auscultation that immediately precedes the first heart sound and is best heard when the patient turns to his left side and holds his breath. The patient’s blood pressure is 150/90 mmHg and his heart rate is 74 beats per minute and regular. He has a long history of hypertension and evidence of extensive calcinosis around the mitral and aortic valves on chest x-ray. The extra sound is most likely due to:a) Increased flow velocity through the aortic valve b) Restricted motion of the aortic valve cusps c) Restricted motion of the mitral valve cusps d) Papillary muscle tension after the rapid filling of the ventricles e) Increased stiffness of the left ventricular wall

• An S4 gallop (also known as an atrial sound or atrial gallop) is a presystolic sound on cardiac auscultation that immediately precedes S1. A left-sided S4 is heard best at the cardiac apex with the patient in the left lateral decubitus position, and a rightsided S4 is heard best along the lower left sternal border (the tricuspid area) with the patient in the supine position.

• An S4 is heard when there is a sudden rise in end diastolic ventricular pressure caused by atrial contraction against a ventricle that has reached the limit of its compliance. Thus, an S4 may be present in any condition that causes a stiff ventricle. Degenerative mitral annular calcification or aortic valve calcification can be associated with chronically elevated LV pressures and systemic hypertension. This patient probably has left ventricular hypertrophy (LVH) associated with hypertensive heart disease. LVH reduces ventricular compliance and can cause diastolic dysfunction.

• A normal atrial contraction is required to generate an S4. (Choice A) This would tend to produce the murmur of aortic stenosis, an ejectiontype murmur that occurs during systole (after S1 and before A2).

• (Choice B) Restricted motion of the aortic valve cusps might be associated with an aortic ejection click, aortic stenosis, and/or aortic regurgitation. In any event, the extra sound(s) produced would occur after S1, during systole.

• (Choice C) Restricted motion of the mitral valve cusps could result in abnormal diastolic sounds, like an opening snap and/or a murmur of mitral stenosis (MS). The opening snap would occur early in diastole. Pre-systolic accentuation (due to atrial contraction) of an otherwise inaudible murmur of MS could explain the extra sound heard in this patient. However, isolated MS is generally associated with normal or reduced left ventricular pressures making degenerative mitral annular calcification as seen in this patient less likely.

• (Choice D)The papillary muscles are not placed under increased tension during diastolic ventricular filling. They are tensed during ventricular systole, after S1.

A 33-year-old Hispanic female who recently emigrated from Mexico is brought to the ER with severe shortness of breath and hemoptysis. She is treated with diuretics, and begins to feel better. However, she develops rightsided hemiparesis soon after. Based on the history and initial physical examination, you suspect mitral stenosis is responsible. Which of the following findings suggests an associated lesion or another diagnosis in this patient?a) Right ventricular dilation b) Increased systolic pulmonary artery pressure c) Increased pulmonary capillary wedge pressure d) Tricuspid regurgitation e) Increased diastolic left ventricular pressure f) Reduced pulmonary compliance

• In isolated mitral stenosis (MS) diastolic pressures in the left ventricle (LV) are usually near normal. Only pressures proximal to the stenotic mitral valve would be markedly elevated.

• When a patient with suspected MS is also found to have an increased LV end diastolic pressure, the presence of an additional lesion is likely. Possibilities include rheumatic involvement of the aortic valve (which typically causes combined aortic stenosis and regurgitation), or infective endocarditis superimposed on an aortic valve deformed by chronic rheumatic heart disease (RHD).

• In patients with RHDI the mitral valve alone is the sole site of involvement in 65% to 70% of cases. Both the mitral and aortic valves are affected in about 25% of cases. This patient’s right-sided hemiparesis may have arisen from an embolic stroke complicating isolated MS (via atrial dilatation, atrial mural thrombosis and thromboembolism) or from an aortic valve vegetation generated by endocarditis. (Choice A) Right ventricular dilatation is found in mitral stenosis that is severe enough to cause significant pulmonary hypertension.

• (Choice B) This finding would be expected in isolated mitral stenosis severe enough to cause significant pulmonary hypertension via backward transmission of elevated left atrial pressure.

• (Choice C) This finding would be expected in isolated mitral stenosis (MS) severe enough to cause a significant elevation of left atrial pressure. A properly measured pulmonary capillary wedge pressure reflects the left atrial transmural pressure at end diastole, which is elevated in MS, even though left ventricular end diastolic transmural pressure (LVEDP) may be normal. Note that the wedge pressure does not reflect LVEDP in patients with MS.

• (Choice D) Tricuspid regurgitation may occur as a complication of severe isolated mitral stenosis, as a consequence of right ventricular dilatation due to pulmonary hypertension.

• (Choice F) Reduced pulmonary vascular compliance may complicate long-standing pulmonary hypertension induced by isolated mitral stenosis. Pulmonary vascular endothelial dysfunction and reactive vasoconstriction can result from pulmonary hypertension. Chronic pulmonary hypertension can also cause reactive hypertrophy in the walls of pulmonary vessels (pulmonary vascular sclerosis). Both of these processes reduce pulmonary vascular compliance.

A 46-year-old Caucasian female presents to your office because of easy fatigability and exertional dyspnea. Auscultation of the heart reveals a diminished first heart sound and an apical holosystolic murmur radiating to the axilla. Lungs have bibasilar crackles. There is no elevation of jugular venous pressure or peripheral edema. Which of the following would most likely increase forward-toregurgitant volume ratio in this patient? a) Decreasing left ventricular preload b) Increasing left ventricular contractility c) Decreasing left ventricular afterload d) Decreasing heart rate e) Increasing left ventricular volume

A 46-year-old Caucasian female presents to your office because of easy fatigability and exertional dyspnea. Auscultation of the heart reveals a diminished first heart sound and an apical holosystolic murmur radiating to the axilla. Lungs have bibasilar crackles. There is no elevation of jugular venous pressure or peripheral edema. Which of the following would most likely increase forward-to-regurgitant volume ratio in this patient? a) Decreasing left ventricular preload b) Increasing left ventricular contractility c) Decreasing left ventricular afterload d) Decreasing heart rate e) Increasing left ventricular volume

• This patient has clinical features suggestive of mitral regurgitation with left sided heart failure. In a patient with mitral regurgitation, some of the blood in the left ventricle is pumped forward through the aortic valve and is considered the forward stroke volume (FSV) while some is forced backwards through the incompetent mitral valve into the left atrium and is considered the regurgitant stroke volume (RSV).

• If the systolic retrograde flow resistance between the LV and LA, the preload (LV end diastolic volume) and the contractility remain the same, the amount of blood that flows forward and backward is determined by the left ventricular afterload (or systolic intraventricular pressure). The lower the average LV afterload, the lower will be the average systolic pressure gradient driving regurgitant flow into the LA and the lower will be the RSV. Moreover, FSV will be increased. This will increase the forward-to-regurgitant volume ratio. Thus arterial vasodilator therapy, which acts to decrease LV afterload, tends to decrease RSV and increase FSV in patients with MR.

• (Choice A) LV preload reduction might decrease the regurgitant flow fraction if the degree of mitral valve incompetence was LV end diastolic volume dependent (eg. in dilated cardiomyopathy) or if the reduction in LV preload was also accompanied by a slight decrease in LV afterload. However these effects on the regurgitant flow fraction would generally be quantitatively less than that of a significant reduction of afterload.

• (Choice B) For a fixed anatomical degree of mitral valve incompetence producing mitral regurgitation (MR) and at a given left ventricular preload, an increase in LV contractility would tend to increase LV afterload. The latter would tend to increase the fraction of each LV stroke volume going into regurgitant flow. Thus an isolated increase in LV contractility would tend to increase MR. Partly for this reason some experts recommend chronic beta blocker therapy for patients with significant MR.

• (Choice D) A primary decrease in heart rate (HR) would tend to increase LV end diastolic volume (preload). In the new steady state after recruitment of cardiovascular reflexes to maintain forward LV output and mean systemic arterial pressure LV afterload might not be significantly changed. Moreover in some cases of MR where LV dilatation alone maybe responsible the fraction of regurgitant flow can increase as the LV dilates further (as preload is increased). Under these conditions a primary decrease in heart rate could decrease the forward to regurgitant LV output ratio.

• (Choice E) Presumably this choice means increasing LV end diastolic volume or preload. As explained above increasing LV preload does not significantly alter steady state LV afterload, the major determinant of the degree of mitral regurgitation. Moreover LV dilatation alone can contribute to or worsen MR.

A 63-year-old Caucasian male presents to the emergency department with severe dyspnea, orthopnea and fatigue. He suffered a myocardial infarction six months ago, and has not been compliant with his medications since that time. On exam, his blood pressure is 170/100 mmHg and his heart rate is 100 beats per minute. Auscultation reveals crackles at the lung bases, an S3 gallop, and a Il/VI holosystolic murmur over the apex. After initial treatment with diuretics and vasodilators the patient’s condition improves significantly. The next morning, there are no appreciable gallops or murmurs on cardiac exam. The murmur heard at presentation is likely explained by:a) Thickened and deformed mitral valve cusps b) Heavily calcified mitral annulus c) Increased flow rate through the aortic valve d) Ruptured chorda tendineae e) Functional mitral regurgitation

• This patient’s symptoms of dyspnea and orthopnea together with bibasilar crackles are consistent with high pulmonary venous pressure and pulmonary edema in the dependent lung. The holosystolic murmur heard over the cardiac apex is suggestive of mitral regurgitation (MR). An 33 gallop reflects an increased left ventricular filling rate during mid diastole, and can be heard as a consequence of MR. • Treatment with a diuretic tends to reduce left ventricular (LV) preload and

therefore decreases the LV end diastolic volume (EDV). Since the patient’s murmur and gallop disappeared following the reduction of LVEDVI his MR was most likely functional— that is, due to transient hemodynamic factors causing LV dilatation and/or papillary muscle ischemia rather than due to a fixed mitral valve lesion.

• Acute LV dilatation can sufficiently separate otherwise normal mitral valve leaflets to permit functional regurgitation. The most common anatomical abnormality producing mitral regurgitation is myxomatous degeneration (mitral valve prolapse). Afterload reduction with a vasodilator decreases the average intraventricular systolic pressure required to generate a given stroke volume and would tend to reduce MR due to any cause. • (Choice A) Thickened and deformed mitral valve cusps are fixed

anatomical lesions that typically result from chronic rheumatic heart disease. For this reason, these lesions are usually only found in older individuals (who may not have had access to antibiotics while young). Mitral stenosis is the usual result.

• (Choice C) Mitral annular calcification, consisting of degenerative calcific deposits in the fibrous ring of the mitral valve, generally does not impair valvular function. There is associated regurgitation or stenosis only in rare instances. Mitral annular calcification is most common in women older than 60, individuals with a history of myxomatous degeneration of the mitral valve, and individuals with chronically elevated left ventricular (LV) pressures. Furthermore, whereas the patient in the vignette had mitral regurgitation that was eliminated by a reduction in LV size (which also decreases the mitral valve radius), the radius is fixed in patients with a calcified mitral valve annulus. • (Choice D) An increased rate of flow through the aortic valve could produce a

functional murmur of aortic stenosis, which would be a systolic ejection type murmur heard best over the aortic area (right upper sternal border).

• (Choice E) Chordae tendineae rupture producing severe mitral regurgitation (MR) is a complication of bacterial endocarditis, and less frequently of connective tissue diseases or acute myocardial infarction. When papillary muscle or chordae rupture occurs in association with myocardial infarction, it is usually an early complication of the Ml (i.e. occurring within 10 days).• The MR of the patient in the vignette appears to have been precipitated by

medication non-compliance which caused an acute hemodynamic change. Thus endocarditis and connective tissue disease are more remote possibilities. Additionally, the murmur of MR due to chordae rupture may not be completely eliminated by pharmacological manipulations. Chordae rupture results in fixed anatomic (versus reversible functional) MR.

A 34-year-old immigrant from South Asia presents to your office complaining of heart palpitations that are particularly prominent at night. He also notes that with moderate exertion, he experiences head “pounding” accompanied by involuntary head bobbing. He remembers being diagnosed with a heart murmur years before, but he cannot recall the type and has never received any treatment. Based on this patient’s history, you suspect:a) Restricted left ventricular filling b) Impaired left ventricular contractility c) Left ventricular outflow obstruction d) Systolic-diastolic hypertension e) Widening of the pulse pressure

• This patient complains of nocturnal palpitations and head pounding with exertion. Palpitations may result from forceful ventricular contractions ejecting large stroke volumes, and head pounding can be due to unusually high amplitude pulsations of the intracranial arteries with each heartbeat. In voluntary head bobbing can be a sign of a widened pulse pressure (recall that pulse pressure = peak systolic arterial pressure — end diastolic arterial pressure). The most likely cause of a repetitive, widened pulse pressure together with unusually large LV stroke volumes and a heart murmur is aortic regurgitation (AR). • (Choice A) Restriction of left ventricular (LV) filling would result in a reduced LV

end diastolic volume (reduced preload). At a given level of contractility, this would cause a reduction in stroke volume. Lower stroke volumes result in lower pulse pressures, whereas this patient’s symptoms and signs suggest a high pulse pressure.

• (Choice B) Impaired left ventricular contractility would cause a reduction in stroke volume for a given preload, resulting in lower pulse pressures. • (Choice C) Left ventricular outflow tract obstruction, as can result

from aortic stenosis or hypertrophic cardiomyopathy, could cause a murmur but would tend to reduce stroke volume and thus pulse pressure. • (Choice D) Combined systolic and diastolic hypertension is not

necessarily accompanied by an abnormally large pulse pressure or murmur.

A 54-year-old Caucasian female presents to your office with exertional dyspnea and fatigue. She also describes nocturnal episodes of dyspnea and orthopnea. After initial evaluation cardiac catheterization was performed that reveals the following findings (see the diagram below). The pressure tracings shown in the diagram are most consistent with which of the following? a) Aortic stenosis b) Aortic regurgitation c) Mitral stenosis d) Mitral regurgitation e) Normal findings

• This patient presents with nonspecific symptoms consistent with an inadequate ability to increase cardiac output during exertion as well as elevated pressures in the pulmonary circulation resulting in a degree of pulmonary edema. The v wave corresponding to left atrial filling during the patient’s cardiac catheterization is abnormal. See graph below.

• Note that the peak v wave pressure corresponding to maximal left atrial filling just prior to the opening of the mitral valve (arrowheads) is elevated. These abnormalities are indicative of mitral regurgitation, with abnormal retrograde filling of the left atrium during ventricular systole.

• (Choice A) The major hemodynamic finding in a patient with aortic stenosis would be a pressure difference (gradient) between the left ventricle and the aorta in the interval delimited by points A and B on the graph in the explanation under (Choice D). A corresponds to opening of the aortic valve and B corresponds to its closure. Left ventricular pressure would be significantly higher than aortic pressure during the A-B interval.

• (Choice B) Aortic regurgitation would tend to elevate both the left ventricular (LV) and left atrial diastolic pressures above their normal values. However the contour of the left atrial pressure tracing relative to the LV pressure curve would not be significantly altered—as it is altered in this patient.

• (Choice C) Mitral stenosis affects the hemodynamic profile during cardiac catheterization as shown below. • Note the pressure gradient between the left atrium and left ventricle

during diastole (arrows). • (Choice E) Only the aortic and left ventricular pressure tracings in this

patient have a grossly normal relationship.

A 44-year-old Caucasian male is successfully treated for infective endocarditis with a long course of antibiotics. Echocardiographic evaluation reveals significant aortic regurgitation as a consequence of the infection. Which of the following is the major hemodynamic compensation for this valvular abnormality?a) Increase in left ventricular afterload b) Increase in left ventricular preload c) Concentric left ventricular hypertrophy d) Sustained increase in heart rate e) Decrease in aortic elasticity

• In a patient with relatively acute aortic regurgitation, the major hemodynamic adaptation to maintain cardiac output is an increase in the left ventricular end diastolic volume (EDV). Assuming no acute decrease in contractility, this preload increase allows forward LV stroke volume (FSV) in the new steady state to remain adequate, although reduced from normal.

• (Choice A) Left ventricular (LV) afterload is already increased in acute aortic regurgitation (AR), and is associated with a greatly increased LV total stroke volume and a widened pulse pressure. A further increase in afterload would increase the regurgitant stroke volume and further decrease the LV forward stroke volume (FSV), thereby further reducing cardiac output. This is why medical stabilization of patients with severe acute AR may include administration of a vasodilator (nitroprusside) in addition to an intravenous positive inotropic agent (dopamine or dobutamine). The vasodilator decreases after load in order to improve the FSV.

• (Choice C) Aortic regurgitation subjects the left ventricle (LV) to volume overload, not pressure overload. The adaptation to volume overload is eccentric hypertrophy, i.e. chamber dilation (due to increased end diastolic volume, EDV) with predominantly “in series synthesis” of new myocardial sarcomeres. Concentric hypertrophy, the response to pressure overload, involves “in parallel deposition” of new sarcomeres, which produces net ventricular wall thickening and a reduction in ventricular chamber size (decreased EDV). Pressure overload may occur in aortic stenosis or systemic hypertension.

• (Choice D) This patient’s relatively acute aortic regurgitation (AR) would decrease the left ventricular forward stroke volume. The acute compensatory response to maintain cardiac output would include an increase heart rate. Patients with acute AR are usually tachycardic and poorly tolerant of lower heart rates. • However this answer choice describes a sustained increase in heart rate. As the

heart of a patient who survives acute AR adapts to volume overload, increased left ventricular end diastolic volume (LVEDV) and eccentric LV hypertrophy result in progressive increases in LV forward stroke volume. Heart rate therefore returns toward normal in chronic AR, so that sustained tachycardia is not the major final hemodynamic compensation. • (Choice E) A decrease in aortic elasticity would tend to increase afterload. An

increase in afterload would further decrease net left ventricular (cardiac) output.

A 45-year-old Caucasian female is hospitalized with exertional dyspnea and fatigue. She recently emigrated from Eastern Europe and has no significant past medical history. Her blood pressure is 110/80 mmHg and her heart rate is 90 beats per minute and regular. You suspect mitral stenosis. Which of the following is the best indicator of the severity of stenosis?a) Diastolic murmur intensity b) Presystolic accentuation of the murmur c) S2-to-opening snap time interval d) Audible S3 e) Audible S4

• The best auscultatory indicator of the severity of mitral stenosis (MS) is the length of the interval between A2 and the opening snap (OS). The shorter the interval the more severe the stenosis. The OS occurs due to tensing of the mitral valve (MV) leaflets after the valve cusps have completed their opening excursion. The more thickened and fibrotic the MV the earlier this tensing occurs. The A2-OS interval is also inversely correlated with mean diastolic left atrial pressure. (In modern practice the standard for the diagnosis and determination of MS severity is measurement of mean transvalvular pressure gradients via 2-D Doppler echocardiography).

• (Choice A) Although the intensity of the diastolic rumble of mitral stenosis (MS) may increase as the degree of MS increases this sign is a less reliable indicator of MS severity. This is because the transmission of the flow murmur at a given transvalvular pressure gradient varies among patients depending upon thoracic anatomy. The diastolic rumble is heard best at the cardiac apex (mitral area) with the bell of a stethoscope.

• (Choice B) There is presystolic accentuation of the murmur of mitral stenosis (MS) because of the increased transvalvular flow associated with left atrial contraction. This accentuation is heard across a range of MS severity. More significant than the degree of presystolic accentuation is its presence or absence. When MS becomes severe enough to precipitate atrial fibrillation, presystolic accentuation of the MS murmur disappears.

• (Choices D and E) Left-sided SS and/or S4 gallops are generally absent in mitral stenosis (MS), since left ventricular filling is subnormal to normal. When MS is severe enough to produce pulmonary hypertension, patients may develop rightsided heart failure, with dilatation of the right ventricle (RV) and its annulus and possible secondary tricuspid or pulmonic regurgitation. Tricuspid and pulmonic regurgitation might cause a right-sided S3 and/or S4. However these EN gallops would only arise when the maximal degree of MS had been reached and thus are poor indicators of the severity of less serious MS.

A 52-year-old Caucasian male presents to your office with two week history of progressive fatigue and exertional dyspnea. He brings with him the report from a recent cardiac catheterization (shown below). Cardiac auscultation reveals a murmur that is best heard when the patient sits up and leans forward. Which of the time points pictured below corresponds to the peak murmur intensity? a) Ab) Bc) Cd) De) E

• Cardiac catheterization shows a hemodynamic profile consistent with aortic regurgitation (AR). Note the high peaking left ventricular and aortic pressures during systole and the steep diastolic decline in aortic pressure. A normal catheterization report is shown below for purposes of comparison:

• The peak intensity of an AR murmur occurs after closure of the incompetent aortic valve, at the point when the pressure gradient between the aorta and the left ventricle is at its maximum i.e. time C. • (Choice A) This time point corresponds to the opening of the aortic

valve during systole. The murmur of aortic stenosis would be heard best here. • (Choice B) This point corresponds to the closure of the aortic valve.

The A2 heart sound is heard here. At this instant there is not yet regurgitant flow from the aorta to the left ventricle, so no murmurs are audible.

• (Choice D) Time point D occurs in mid-diastole. The murmur of AR might be heard here, as there is a pressure gradient between the aorta and left ventricle (LV). However the intensity of the murmur would be less than at time C because the magnitude of the gradient is less. Because the AR murmur decreases in intensity with the falling aortic pressure, it is a “decrescendo” diastolic murmur. • (Choice E)Time E marks the onset of left atrial contraction at the end

of ventricular diastole. If the murmur of AR were still audible at this time, its intensity would be further reduced by the increase in left ventricular end diastolic pressure.