Severe Aortic Stenosis Case File

Severe Aortic Stenosis Case File

Eugene C. Toy, Md, Michael d . Faulx, Md

Case 10

A 67-year-old man with a history of hyperlipidemia and hypertension is evaluated in the emergency room after a syncopal event. He was mowing the lawn. became “winded” and suddenly “blacked out.” He remarks that he has had two other episodes of syncope over the past 3 months, and has developed occasional exertional chest discomfort over the past year. His medications include lisinopril and simvastatin. On assessment. vitals are BP 146/87 mmHg, HR 102 bpm and irregular. with normal respirations at 14 breaths/min. Examination is notable for a III/VI late-peaking systolic murmur most audible at the right upper sternal border, which obliterates the second heart sound and radiates to the carotid arteries. His carotid pulse is blunted, and the upstroke is delayed compared to his heart sounds on auscultation.

c What is the most likely diagnosis?

c What the best next diagnostic steps?

c What is the best treatment?

Answer to Case 10:

Severe Aortic Stenosis

Summary: This 67-year-old man presents with recurrent syncope in the setting of exertional dyspnea and intermittent exertional chest discomfort. His presentation indicates possible valvular pathology, and his examination suggests severe aortic valve stenosis. In view of his symptoms and physical examination, he has a clear indication for aortic valve replacement.

• Most likely diagnosis: Severe aortic stenosis.
• Next diagnostic step: Transthoracic echocardiogram (TTE).
• Best treatment: Aortic valve replacement.

ANALYSIS

Objectives

1. Understand the presentation and basic pathophysiology of valvular stenoses, including aortic stenosis, mitral stenosis, pulmonary stenosis, and tricuspid stenosis.
2. Understand the diagnosis and natural history of aortic stenosis and mitral stenosis.
3. Understand the medical, percutaneous, and surgical treatments for aortic stenosis and mitral stenosis.

Considerations

This 67-year-old man presents with classic findings of severe aortic stenosis. Valvular stenosis can be separated into left-sided stenoses (aortic and mitral valves) and right-sided stenoses (pulmonary and tricuspid valves). In this case study, the various valvular stenoses will be discussed individually. As aortic stenosis is the most common valvular stenosis encountered in clinical practice, it will be the focus of this case.

Approach To:

Valvular Stenosis

DEFINITIONS

AFTERLOAD: The tension in the left ventricular wall developed during systole, or more simply, the load against which the heart beats. Typically refers to systemic vascular resistance of the arterial system; however, it may be fixed in the setting of aortic or mitral stenosis.

PRELOAD: The volume of the right or left ventricle at end diastole, or more simply, the stretching of the myocardium due to filling of the heart. Preload reflects the volume status of the patient; it is high in states of volume overload, and low when dehydrated or hypovolemic.

VALVULAR STENOSIS: Narrowing of the valvular orifice, due to restriction of the opening of the valvular leaflets, which causes obstruction of flow.

CLINICAL APPROACH

Aortic Stenosis

Etiology Aortic stenosis (AS) is the most common cause of left ventricular outflow obstruction in adults. The three most common etiologies of AS are calcific disease of a trileaflet (normal) aortic valve, superimposed calcification of a congenitally abnormal (ie, bicuspid) valve, and sequelae of rheumatic fever. Although rheumatic disease is the most common cause worldwide, calcific disease is most prevalent in North America and Europe.

Pathophysiology Rheumatic valve disease is typically caused by untreated infection, usually group A Streptococcus. Antibodies formed against the bacteria attack the valve, causing fusion of the commissures between the leaflets, and resultant stenosis. Calcific aortic valve disease of a normal trileaflet or congenitally bicuspid aortic valve is caused by gradual lipid accumulation, inflammation, and eventual calcification, which causes aortic sclerosis. Eventually, the calcified leaflets become thickened and stiff, and do not open fully during systole. The disease process is accelerated as mechanical stress and shear force gradually wear on the valve. Although AS shares several risk factors with atherosclerosis, studies have shown that therapies to treat atherosclerosis (ie, statins) do not slow the progression of AS once mild disease is present.

The effective opening aortic valve area (AVA) in a healthy individual is 3.0–4.0 cm². Aortic sclerosis is defined as valve narrowing that is < 3.0 cm² but >1.5 cm², with a jet velocity of ≤2.5 cm². Aortic stenosis is officially defined once AVA reaches <1.5 cm² and the jet velocity is >2.6 cm². Obstruction to flow does not occur until AVA is <1.5 cm², and symptoms do not typically occur until AS is severe, at <1.0 cm². Grading to the severity of aortic stenosis is based on the valve area and pressure gradients across the valve, as shown in Table 10-1.

*Critical AS if aortic valve area is < 0.6–0.7 cm².

When AS becomes hemodynamically significant, it causes a fixed increase in LV afterload, which over time results in left ventricular hypertrophy (LVH). This further decreases LV compliance, increases LV end diastolic pressure, and promotes diastolic dysfunction (or more simply, problems with the heart filling). Diastolic dysfunction and subendocardial ischemia may contribute to a loss of LV function and eventual decline in ejection fraction.

Clinical Presentation Understanding the pathophysiology of AS allows for an easy understanding of its symptoms. As diastolic dysfunction progresses, the coronary arteries may not fill adequately, and LVH may cause the myocardium to outgrow the blood supply of the small capillaries of the heart, leading to angina. As the stenosis, LVH, and diastolic dysfunction worsen, symptoms of dyspnea on exertion and leftsided heart failure may develop. Further, the fixed obstruction to flow caused by AS may make it difficult for cardiac output to appropriately increase during exercise. As peripheral vasodilation occurs during exercise, blood pressure may fall, which may lead to decreased cerebral perfusion and syncope.

Physical examination The murmur of AS is classically described as a systolic “ejection” murmur, heard best at the base of the heart at the right 2nd intercostal space with radiation to the carotids. The murmur may begin with an “ejection click” in systole, and typically grows louder and then softer by the end of systole (a so-called crescendo-decrescend quality). As the aortic valve area (AVA) decreases, the peak of the murmur moves closer to S2, eventually softening or obliterating S2 altogether. Further, an LV thrill may be palpated, and the point of maximal impulse may be laterally displaced. Additionally, as a result of the LV outflow tract obstruction, the carotid pulse may be weak and its rise delayed compared to auscultation of cardiac injection during systole (termed pulsus parvus et tardus). The examination findings most predictive of severe AS are pulsus parvus et tardus, a mid-to-latepeaking systolic ejection murmur, and a reduced intensity of the 2nd heart sound.

Differential Diagnosis The murmur of AS may be confused for aortic sclerosis or obstructive hypertrophic cardiomyopathy (HCM). The murmur of aortic sclerosis shares many similar features with AS; however, it typically does not radiate to the carotids or obliterate the 2nd heart sound. The HCM murmur may be indistinguishable from AS; however, with maneuvers that decrease preload (ie, standing from a sitting position), the HCM murmur typically increases, and with maneuvers that increase preload (Valsalva maneuver, leg raise), the HCM murmur typically decreases. Neither maneuver typically affects AS.

Diagnostic Approach Obtaining a transthoracic echocardiogram allows for formal assessment of the AVA, mean and peak gradients, and valve structure (ie, whether it is tricuspid or bicuspid). Concurrent aortic regurgitation is present in over 80% of patients with AS, and can be further assessed with echocardiography. Further, the aortic root, ascending aorta, and presence of an aortic coarctation may be measured by echocardiography. This is especially important in patients with a bicuspid aortic valve, as there is a strong association with aortic root disease and coarctation of the aorta.

Additional tests that are often obtained in patients with AS are an ECG (may show LVH), CXR, and transesophageal echocardiogram. Cardiac catheterization may be used to formally measure the valve area, and may be requested prior to valve surgery to evaluate whether coronary artery bypass grafting (CABG) needs to be done at the same time.

Treatment Medical treatment of AS is challenging, and there are currently no effective medical therapies that reverse aortic stenosis. Concomitant hypertension may lead to the development of symptoms at earlier stages of AS; therefore, antihypertensive medications such as ACE inhibitors should be considered and titrated carefully to avoid large fluctuations in blood pressure. Although the cardiac output is not completely “fixed” in severe aortic stenosis, it is limited and hypotension is poorly tolerated in patients with advanced AS, so aggressive blood pressure lowering should be avoided. Patients with atrial fibrillation benefit from heart rate control with beta-blockers, as rapid ventricular response may impair LV filling in the setting of diastolic dysfunction, and lead to pulmonary edema. Patients with heart failure should receive diuretic therapy as necessary, but care should be taken to avoid hypovolemia, as patients may depend on preload for maintenance of their cardiac output. Additionally, nitrates and vasodilators should be used cautiously to avoid decreasing preload for this reason.

Given the limited utility of medical management in AS, surgical and catheterbased therapies are the mainstays of treatment. Balloon aortic valvuloplasty may be considered in patients with severe AS who are not candidates for conventional aortic valve surgery or transcatheter valve replacement. In this procedure an arterial access sheath is placed, typically in the femoral artery, and a catheter outfitted with a noncompliant balloon is placed inside the stenosis valve orifice over a guidewire. The balloon is then inflated during a period of rapid right ventricular pacing via a transvenous pacing wire in order to transiently halt cardiac outflow while the balloon is inflated. Balloon valvuloplasty may allow for immediate improvement in symptoms, but results are typically not durable past 6 months, and as such the procedure is reserved for palliation and bridge to more permanent therapies.

Because of the limitations of valvuloplasty, aortic valve replacement is the standard of care for severe AS. Major indications for surgery include the onset of symptoms, patients undergoing CABG or other cardiovascular surgery, or an LVEF of <50%. Additionally, asymptomatic patients whose symptoms are provoked during stress testing are often referred for surgery. The valve is then replaced via an open or minimally invasive approach with a bioprosthetic (cadaver, bovine, or porcine) or mechanical (metal) material. Bioprosthetic valves hold the advantage of needing anticoagulation for only 3 months following surgery, while mechanical valves require lifelong anticoagulation [international normalized ratio (INR) 2–3 for bileaflet disk valves, INR 2.5–3.5 for tilting disk or caged ball valves). However, bioprosthetic valves are less durable than mechanical valves. Although durability is difficult to accurately predict, patients receiving bioprosthetic valves have a 25% lifetime risk for reoperation versus <5% for mechanical valves.

Patients with severe AS who are not candidates or high risk for surgery may be considered for transcatheter aortic valve replacement (TAVR). The pivotal study

figure 10-1. Transcatheter aortic valve replacement (TAVR). A bioprosthetic valve is crimped onto a

deflated angioplasty balloon and delivered to the ascending aorta from an introducer sheath in the

femoral artery (a). The compressed prosthesis is moved into position within the native aortic valve

using radiographic and trans esophageal echocardiographic guidance (b). during a period of rapid

electrical pacing from the right ventricle, the balloon is inflated, expanding the prosthesis, which

then holds its shape as it pushes the native valve into the aortic wall (c). The balloon is deflated and

the delivery system is withdrawn, leaving the prosthesis in place and functional (d). (Reprinted with

permission, Cleveland Clinic Center for Medical Art & Photography © 2013. All rights reserved.)

evaluating this technique was the PARTNER (Placement of AoRtic TraNscathetER valves) trial, which showed that TAVR was superior to medical treatment and noninferior to surgical valve replacement for patients with severe AS. This is a catheter-based therapy, which follows similar steps as an aortic valvuloplasty; however, following the valuloplasty, an expandable stent containing a bioprosthetic heart valve is placed over the diseased aortic valve (Figure 10-1). The transfemoral approach is utilized most commonly; however, other access options include access via the subclavian artery, and via surgical puncture of the cardiac apex.

Prognosis Patients with a congenitally bicuspid aortic valve are typically asymptomatic for decades, until the calcification and leaflet restriction cause obstruction and symptoms. Regardless of the underlying etiology of AS, the average survival for patients once symptoms develop is low: angina (5 years), syncope (3 years), and heart failure (2 years). Following valve replacement, life expectancy and quality of life are generally good, approaching age-matched controls with similar comorbidities.

Mitral Stenosis

Pathophysiology Mitral stenosis (MS) is caused by thickening and restriction of the valve leaflets, causing obstruction of blood flow into the LV, increased pressure in the LA, pulmonary vasculature, and right side of the heart. As the LA enlarges, atrial fibrillation may develop. In the majority of cases, MS is caused by rheumatic fever (discussed in the AS section). Congenital MS is the second most common cause; a less frequent cause is severe mitral annular calcification

(particularly in end-stage renal disease). A normal mitral valve area is 3.0–4.0 cm²,

with mild stenosis graded 1.5–2.5 cm²; moderate, 1.0–1.5 cm²; and severe, <1.0 cm². Grading of MS on the basis of valve area and transmitral gradients is summarized in Table 10-2.

Clinical Presentation The classic murmur of MS is a diastolic “opening snap” (OS), followed by a low-pitched diastolic rumble most audible at the cardiac apex. It is best heard in a quiet room with the patient lying in the left lateral decubitus position at end expiration, with the bell of the stethoscope. As MS progresses and the LA pressure is higher, the OS occurs earlier after S2, and thus the shorter the S2-OS interval, the more severe the MS.

Patients with MS often present with symptoms of left-sided heart failure. Chronic MS often leads to pulmonary hypertension, right ventricular hypertrophy, and eventual right-sided heart failure. Thus, the most common symptoms in MS are dyspnea, hemoptysis, atrial fibrillation, systemic thromboembolism, hoarseness, and infective endocarditis. With severe MS, cardiac output is decreased, and the resultant vasoconstriction causes pinkish purple patches on the cheeks, called “mitral facies.” During pregnancy, the increase in preload, heart rate, and cardiac output can increase the resting transmitral gradient, which may lead to symptoms.

Differential Diagnosis Left atrial myxomas, other cardiac tumors, and congenital abnormalities (such as a LA membrane) may cause LA outflow obstruction and symptoms similar to MS. Additionally, radiation heart disease and prior valve replacement may predispose patients to developing MS.

Diagnostic Approach The diagnostic approach to MS is similar to that of AS. TTE is the diagnostic modality of choice, as it allows for measurement of valve gradients and valve area. Further, atrial size and assessment of pulmonary hypertension and right-heart function can be measured with TTE. ECG may show signs of left atrial enlargement, right-axis deviation, and right-heart strain. CXR may be normal, or show left atrial enlargement (LAE) and calcification of the mitral valve. Cardiac catheterization allows for direct measurement of intracardiac pressures and a precise determination of the mitral valve gradient and may be necessary if TTE is inconclusive.

Treatment and Prognosis Medical therapy for MS centers on control of symptoms of left-sided heart failure with diuretic therapy and salt restriction. Patients with atrial fibrillation should be offered rate control with beta-blockers, and digoxin may be added, as this may reduce hospitalization in patients with reduced

EF. Patients who have had a prior thromboembolic event should be anticoagulated to an INR of 2.0–3.0 for life, and some studies suggest the addition of low-dose aspirin as well. The ACC/AHA guidelines suggest that anticoagulation should be considered in patients with severe MS and LAE regardless of prior thromboembolic history.

Patients should be offered mitral valuloplasty or surgery once MS is severe, symptoms are present, or there is evidence of pulmonary hypertension [pulmonary artery systolic pressure (PASP) > 50 mmHg at rest or > 60 mmHg with exercise]. As opposed to AS, percutaneous valvuloplasty is the treatment of choice in most patients with MS, as results are typically more successful and much more durable. Exceptions to this rule are in patients with congenital MS, and in patients with severe (3–4+) mitral regurgitation, in which surgery should be pursued. Percutaneous valvuloplasty and/or surgery may be repeated in the same individual as long as the valve anatomy allows.

Prognosis The natural history of MS is such that patients may have underling MS but be asymptomatic, with a latency period of 20–40 years. Pregnancy should be discouraged in patients with severe MS because there is a significant mortality rate during surgery. Death from MS is typically due to progressive heart failure or systemic thromboembolism as a complication of atrial fibrillation.

Pulmonic Stenosis

Pathophysiology Stenosis of the pulmonary valve is a relatively common congenital defect, but is uncommon in adults. The normal trileaflet pulmonic valve may have partial or complete fusion of any of the valve leaflets, thickening, and narrowing of the valve area. Pulmonic stenosis (PS) is often associated with other congenital abnormalities (such as tetralogy of Fallot). Adults may develop PS as a result of carcinoid syndrome.

Clinical Presentation The murmur of PS is a systolic ejection murmur that is similar to AS, except that it is most audible at the left upper sternal border, and the murmur increases with inspiration. As with AS, the murmur peaks later and becomes louder as the PS worsens. Additionally, patients may have an RV lift, a loud P2, and fixed splitting of the 2nd heart sound as PS worsens. Symptoms of severe pulmonic stenosis include exertional dyspnea, fatigue, chest pain, and syncope.

Diagnostic Approach As with AS, a TTE is the first diagnostic test to order for evaluation of PS. Severe PS is defined as a peak Doppler gradient of >50–60 mmHg, a mean Doppler gradient of >30–40 mmHg, or a peak velocity of >4 m/s. ECG may show signs of right-heart strain (RVH, right-axis deviation, right bundle branch block, and right atrial enlargement or “p-pulmonale”). Likewise, CXR may show right atrial enlargement. Invasive hemodynamic measurement with right-heart catheterization is indicated if the diagnosis is unclear or if pulmonary valvuloplasty is needed.

Treatment and Prognosis Balloon valvuloplasty is recommended in asymptomatc patients with a peak Doppler gradient of >60 mmHg or a mean gradient of >40 mmHg. In symptomatic patients, the peak and mean pressure criteria are each lowered by 10 mmHg (>50 mmHg peak, > 30 mmHg mean). Surgical therapy is recommended in patients with associated severe pulmonary regurgitation, hyoplastic pulmonary annulus, or sub- or supravalvular PS.

Tricuspid Stenosis

Overview Tricuspid stenosis (TS) is uncommon, and is typically associated with other valvular lesions, carcinoid syndrome, or rheumatic heart disease. It is infrequently seen in adults.

The murmur of and overall presentation of TS is similar to MS—there is an opening snap followed by a low-pitched diastolic murmur, but unlike MS, it is heard at the lower left sternal border and increases with inspiration. Obstruction of flow across the tricuspid valve leads to an increase in RA pressure, and jugular venous distention with a prominent A wave and slow y descent. The predominant symptoms

of TS are right-sided heart failure. Like the other valvular lesions discussed, the TTE is utilized for diagnosis. A tricuspid valve area of < 1.0 cm² is indicative of severe TS. Similar to MS, most cases of TS can be treated with balloon valvuloplasty, with surgery reserved for cases refractory to the percutaneous approach.

CASE CORRELATION

• See also Case 8 (hypertrophic obstructive cardiomyopathy).

COMPREHENSION QUESTIONS

10.1 A 78-year-old man presents with occasional syncope with exertion for the last 2 months. Physical exam demonstrates a III/VI late-peaking systolic murmur at the right upper sternal border. The second heart sound is dampened, and the carotid upstroke is delayed. On the basis of the examination, what is the most likely diagnosis?

A. Aortic sclerosis

B. Mild to moderate aortic stenosis

C. Severe aortic stenosis

D. Hypertrophic obstructive cardiomyopathy

E. Severe mitral regurgitation

10.2 An 80-year-old woman with a history of coronary artery disease (treated with three-vessel CABG), severe COPD [forced expiratory volume in 1 second (FEV1) 0.7 L], chronic kidney disease, and type 2 diabetes presents for evaluation of critical AS. She is presently hemodynamically stable but describes

progressive NYHA class 3 dyspnea that limits her active lifestyle. Her echocardiogram shows that her AVA is 0.5 cm² with peak and mean transaortic pressure gradients of 84 mmHg and 56 mmHg, respectively. Which of the following is the best treatment option for this patient?

A. Medical management with beta-blockers and afterload reduction

B. Percutaneous balloon valvuloplasty

C. Transcatheter aortic valve replacement (TAVR)

D. Redo sternotomy and open aortic valve replacement

E. Referral to a hospice

10.3 A 24-year-old woman is admitted to the hospital with acute pulmonary edema and atrial fibrillation with rapid ventricular rate. Examination reveals an early diastolic murmur most audible at the apex. What is the most likely diagnosis?

A. Aortic regurgitation

B. Congenital aortic stenosis

C. Mitral regurgitation

D. Mitral stenosis

10.4 A 36-year-old female is admitted to the hospital with flushing, abdominal pain, and diarrhea for the past week. A CT of the abdomen shows diffuse abdominal lymphadadenopathy, a 2-cm mass in the cecum, and a 1-cm liver mass of uncertain etiology. Physical examination reveals BP 90/54, HR 112 and regular, a II/VI systolic murmur at the left upper sternal border, and right upper quadrant abdominal pain. What is the most likely diagnosis?

A. Hepatocellular carcinoma

B. Carcinoid syndrome

C. Intestinal lymphoma

D. Gastrinoma

ANSWERS

10.1 C. The examination findings are consistent with severe AS. As the stenosis worsens, the murmur becomes late-peaking, obliterating S2, and there may be pulsus parvus et tardus. None of the other valvular abnormalities are described by this patient’s murmur.

10.2 C. TAVR has emerged as the treatment of choice for patients with severe AS who are at high risk for complications related to open-valve replacement. Medical therapy does not improve survival or improve symptoms much in patients with severe AS. Balloon valvuloplasty does not provide complete or durable hemodynamic improvement and is generally used as a palliative procedure or as a “bail out” procedure for critically ill patients who are expected to recover enough to potentially undergo TAVR or open-valve replacement.

10.3 D. This question describes the classic clinical scenario of MS exacerbated by the physiologic changes of pregnancy, including increased preload and pulse. This patient should be diuresed carefully, and monitored closely throughout pregnancy given the high association of morbidity and mortality with MS and pregnancy.

10.4 B. This patient’s symptoms are most consistent with carcinoid syndrome. The symptoms of carcinoid syndrome are due to an excess secretion of seritonin, which causes bronchospasm, diarrhea, sweating, and flushing. As seritonin is metabolized by the liver, these symptoms do not typically present unless carcinoid is metastatic to the liver. Carcinoid is associated with right-sided valvular heart lesions, including pulmonary stenosis, as in this patient.

CLINICAL PEARLS

C Aortic stenosis is classified as severe once AVA< 1.0 cm2, mean gradient > 40 mmHg, and peak gradient> 60 mmHg. Mortality from AS typically occurs within 5 years of the onset of angina, 3 years of syncope, and 2 years of heart failure symptoms.

C The TAVR procedure has been shown to be superior to medical therapy in inoperable patients and non inferior to surgery in high-risk patients with severe AS.

C Percutaneous balloon valvuloplasty may provide temporary relief, but results are not durable in AS, with average duration of procedural success approximately 3-6 months. ln contrast, valvuloplasty is the treatment of choice for MS, as results are typically much more successful and durable.

C Rheumatic fever is the major cause of MS, and may be associated with AS and right-sided valvular stenoses. as well.

C Carcinoid is the most common cause of right-sided valvular stenoses in adults, and typically is not symptomatic unless metastatic to the liver.

References

Baumgartner H, et al. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. Eur J Echocardiogr. 2009;10:1–25. 

Leon MB, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363:1597–1607. 

Smith CR, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med. 2011;2187–2198.

HomeCase FilesSevere Aortic Stenosis Case File