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Clinical Review & Education Clinical Crossroads Asymptomatic Aortic Stenosis in the Elderly A Clinical Review Warren J. Manning, MD IMPORTANCE Aortic stenosis is the most common form of valvular heart disease. Progression of aortic stenosis is very slow and highly variable. Decisions about when to perform valve surgery are made by subjective assessment of patient symptoms and objective measures of the valve and ventricular function by transthoracic echocardiography. CME Quiz at jamanetworkcme.com and CME Questions 1500 OBJECTIVE To review current concepts regarding the development, progression, and assessment of aortic stenosis; the appropriate monitoring intervals for transthoracic echocardiography; and the indications for valve procedures. EVIDENCE REVIEW Guidelines and literature search. FINDINGS Angina, exertional syncope, and heart failure are key symptoms indicating a need for intervention. The frequency of valvular monitoring by transthoracic echocardiography is guided by the disease severity. Despite evidence of severe disease, valve procedures can safely be deferred if patients experience no symptoms and have normal left ventricular ejection fraction. Asymptomatic patients with severe aortic stenosis may subconsciously curtail their activities to avoid symptoms. Apparently, asymptomatic patients can undergo a carefully monitored exercise stress test to confirm both their asymptomatic status and hemodynamic response to exercise. Bioprosthetic valves are a good replacement alternative for older patients who are good surgical candidates and who have no need for warfarin therapy. For patients who are at high or very high risk of cardiac surgery, transcutaneous aortic valve implantation is an increasing available and preferred over medical management. CONCLUSIONS AND RELEVANCE Asymptomatic patients with severe aortic stenosis require frequent monitoring of their subjective symptoms combined with objective measurement of aortic valve gradient and ventricular function by transthoracic echocardiography. Although conventional surgical replacement remains the mainstay of therapy for aortic stenosis, transcutaneous aortic valve implantation options are evolving. JAMA. 2013;310(14):1490-1497. doi:10.1001/jama.2013.279194 This article is based on a conference that took place at the Medicine Grand Rounds at Beth Israel Deaconess Medical Center, Boston, Massachusetts, on March 12, 2009. Case Presentation Dr Libman Dr T is an 85-year-old physician with a history of hypertension and aortic stenosis who was in his usual state of health until 2 months ago, when he noticed mild shortness of breath while walking up an incline. Symptoms did not progress and were inconsistent. He was able to walk on level surfaces and pursue his normal daily activities without difficulty. He denied chest pain, orthopnea, paroxysmal nocturnal dyspnea, peripheral edema, lightheadedness, or syncope. He has no history of coronary artery disease. His 1490 Author Affiliation: Cardiovascular Division, Department of Medicine, and Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Corresponding Author: Warren J. Manning, MD, Cardiovascular Division, 330 Brookline Ave, Boston, MA 02215 ([email protected]). Section Editor: Edward H. Livingston, MD, Deputy Editor, JAMA. past medical history is noteworthy for recurrent skin cancers, restless leg syndrome, chronic constipation, and hyperlipidemia. His current medications include 50 mg of hydrochlorothiazide, 40 mg of lisinopril, 0.25 mg of pramipexole, and 20 mg of simvastatin daily and 50 mg of metoprolol tartrate twice daily. Dr T is married and lives with his wife. He has 2 grown children. He is a semiretired allergist-immunologist. He has 1 to 2 glasses of wine per week. He has no history of cigarette smoking. On examination, his blood pressure was 124/78 mm Hg with a regular pulse of 64/min. Jugular venous pressure was 6 cm; carotid arteries were palpable with slightly delayed upstroke and no bruits. His heart beat at a regular rhythm with normal S1, fixed split S2, and no S3 or S4. There was a grade 3/4 systolic ejection murmur, which was loudest at his right upper sternal border radiating toward the carotids. The point of maximal impulse was not displaced. JAMA October 9, 2013 Volume 310, Number 14 Downloaded From: http://jama.jamanetwork.com/ by a Beth Israel Deaconess Medical Center User on 09/24/2014 jama.com Asymptomatic Aortic Stenosis in the Elderly Clinical Crossroads Clinical Review & Education Figure 1. Dr T's Transthoracic Echocardiogram Continuous Wave Color Doppler Results, August 2008 and January 2009 A August 2008 B January 2009 Aortic valve area Aortic valve peak velocity Aoritc valve peak gradient Aortic valve mean gradient 0.9 cm2 4.1 m/s 67 mm Hg 43 mm Hg A transthoracic echocardiograph, performed 2 months prior, showed mild concentric left ventricular (LV) hypertrophy with normal cavity size and normal regional-global systolic function (ejection fraction, >60%; normal ejection fraction, 55%-70%). Peak gradient across the aortic valve was 97 mm Hg (normal peak gradient, <15 mm Hg), and a calculated aortic valve area of 0.7 cm2 (normal aortic valve area, >3.0 cm2). There was no aortic regurgitation. There was mild mitral regurgitation. Seven months before, his peak gradient was 67 mm Hg, demonstrating that the severity of aortic stenosis had increased (Figure 1). A stress nuclear study a month prior was stopped after 6.75 minutes of a modified Bruce protocol due to fatigue and an asymptomatic reduction in blood pressure from 148/84 mm Hg to 122/68 mm Hg. Electrocardiograph showed 2 to 2.5 mm of upslopinghorizontal ST segment depression inferolaterally, which became downsloping in recovery. The nuclear study was interpreted as “probably normal myocardial perfusion.” Dr T was diagnosed with severe aortic stenosis. In light of his ability to function well and in the absence of rest symptoms or reduction in LV function, it was decided to monitor him clinically for the present time. Dr T: His View I was diagnosed with a heart murmur, which was compatible with aortic stenosis about 8 or 10 years ago. I was asymptomatic at that time. The first symptom I had was this past summer, when I was climbing a steep hill to my summer house. I noticed that I was getting extraordinarily short of breath. I continue, however, to go to the gym at least 3 times a week and work out for 20 to 30 minutes on elliptical machines without symptoms. I talked to my primary care jama.com Aortic valve area Aortic valve peak velocity Aoritc valve peak gradient Aortic valve mean gradient 0.7 cm2 4.9 m/s 97 mm Hg 68 mm Hg physician who suggested that we get another echocardiograph, which showed severe aortic stenosis. I was obviously concerned. I live a very active lifestyle for someone who is 85. I see patients on a part time basis, go to school, and live actively. I am concerned that at some point, I will become symptomatic, and then I will have to get a valve replacement. I know that my doctors havesuggestedwatchfulwaiting,butIamwonderinggivenmyageand generally good health whether I should proceed with surgery now. Epidemiology and Etiology of Aortic Stenosis Dr Manning Dr T is a relatively active 85-year-old gentleman who shares a valvular pathology with many older adults. He is fortunate tohavelivedtoanerainwhichnoninvasiveimagingtechnologyisreadily available both to diagnose and to monitor this common disorder. In addition, highly successful treatment options are widely available. Given the increase in longevity afforded by other advances in health care, degenerative calcified aortic stenosis has now become the most common form of valvular heart disease in the Western World with a prevalence of 3% of those 75 years or older, and representing a major health care burden that is projected to increase with an aging population.1 There is ongoing basic science and clinical research to further our understanding of its pathogenesis and management.2 Although we often think of aortic stenosis as fixed obstructive aortic valve disease, a similar presentation, albeit in a younger population, may occur with supravalvular and subvalvular membranes. These “nonvalvular but fixed” obstructive conditions may present in a similar manner and are readily distinguished by transthoracic echocardiography. Aortic stenosis is characterized by a progressive narrowing of the aortic valve that leads to a pressure overload state on the LV. ValJAMA October 9, 2013 Volume 310, Number 14 Downloaded From: http://jama.jamanetwork.com/ by a Beth Israel Deaconess Medical Center User on 09/24/2014 1491 Clinical Review & Education Clinical Crossroads Asymptomatic Aortic Stenosis in the Elderly Figure 2. Normal and Stenotic Aortic Valve Morphologies A Normal heart valve anatomy B Examples of types of aortic stenosis and age of presentation of aortic stenosis ANTERIOR Left coronary artery (LCA) Right coronary artery (RCA) PULMONARY VA LV E Degenerative calcific aortic stenosis (elderly [>70 yrs]) LCA Aortic valve Rheumatic aortic stenosis (young and middle-aged adults) LCA RCA RCA Valve area LEF T ATRIOVENTRICULAR VALVE RIGHT ATRIOVENTRICULAR VALVE Bicuspid aortic stenosis (young and middle-aged adultsa) LCA RCA Unicuspid aortic stenosis (infants and children) LCA RCA Coronary sinus POSTERIOR a Most common congenital cardiac anomaly in adults (men > women)1; also occurs secondary to thoracic aorta anomalies (aneurysm, dissection, or coarctation) vular aortic stenosis has several etiologies that typically present in different age groups, including unicuspid, bicuspid, and trileaflet aortic stenosis (Figure 2). Rheumatic aortic stenosis leads to leaflet thickening and fusion with a progressively narrow, “oval” residual orifice. Patients with degenerative calcific aortic stenosis are typically older (>70 years), and the residual orifice retains a Y or branch opening configuration. The pathophysiology of degenerative calcific aortic stenosis is not a passive process reflecting the inevitable consequence of aging but is the result of a biologically active process with characteristic features of an osteoblast phenotype.3 Risk factors for disease progression mirror those of coronary artery disease. Of those risk factors, Dr T has advanced age, hypertension, and hyperlipidemia.4 Other risk factors include diabetes, smoking, and renal dysfunction. An inflammatory basis for aortic stenosis is supported by studies demonstrating increasing 18-fluorodeoxyglucose levels, a positron emission tomographic ligand marker of macrophage activity, with increasing valve stenosis severity.5 Symptoms and Signs An increase in the aortic valve gradient results in pressure overload and concentric LV wall thickening or hypertrophy with preservation of LV cavitysizeandejectionfraction—aswasseeninDrT’stransthoracicechocardiograph. Despite a preserved ejection fraction, subclinical abnormalitiesofsystolicfunctionmaybepresentandidentifiedbyassessment of LV strain.6,7 The hypertrophy and associated fibrosis8 likely contributes to LV diastolic dysfunction and increased filling pressure. In a subset of patients with severe aortic stenosis, LV hypertrophy is absent.9 The 3 cardinal symptoms of aortic stenosis indicating a need for mechanical intervention are angina, exertional syncope or presyncope, and heart failure (eg, exertional cardiac dyspnea, orthopnea, 1492 paroxysmal nocturnal dyspnea, pedal edema). Heart failure is the result of LV hypertrophy with fibrosis8 and diastolic dysfunction, with increased filling pressure, often despite preserved LV ejection fraction; exertional syncope or presyncope is the result of peripheral vasodilation with an inability of the heart to increase stroke volume; and angina is the result of increased myocardial muscle and increased myocardial demand with limited coronary blood supply without or with obstructive coronary artery disease. Exertional angina may be present in up to 50% of patients with aortic stenosis despite the absence of obstructive coronary artery disease.10 Physical examination findings include a delayed carotid upstroke (pulsus parvus et tardus or slowly rising carotid upstroke; a finding that is often absent in older persons) and a sustained point of maximal impulse due to LV hypertrophy. Auscultation demonstrates a normal or accentuated S1, followed by a harsh, late-peaking systolic murmur (an exampleofthesoundisavailableathttp://www.dundee.ac.uk/medther /Cardiology/as.htm) that is best heard in the right or left upper sternal border and is transmitted to the right clavicular area and carotids (compared with the murmur of mitral regurgitation that is best heard at the left lower sternal border, peaks earlier, and radiates to the axilla and back). As the severity of aortic stenosis progresses, the murmur peaks later in systole or may even decrease in intensity as stroke volume declines. The aortic component of S2 is soft or absent in severe aortic stenosis. Although I have not had the opportunity to examine Dr T, I suspect the aortic valve closure component of S2 was minimal or absent. Criteria for Climactically Significant Aortic Stenosis The normal aortic valve has 3 thin, highly mobile leaflets that provide a valve opening of 3 to 4 cm2 and minimal gradient (<10 mm Hg). Progression of aortic stenosis in the early stages is very slow, JAMA October 9, 2013 Volume 310, Number 14 Downloaded From: http://jama.jamanetwork.com/ by a Beth Israel Deaconess Medical Center User on 09/24/2014 jama.com Asymptomatic Aortic Stenosis in the Elderly Clinical Crossroads Clinical Review & Education Table 1. Clinical Data From Serial Echocardiographic Studies Performed on Dr T Peak velocity, m/s March 18, 2003 3.4 September 19, 2005 3.3 August 6, 2008 4.1 January 21, 2009 4.9 Gradient, mm Hg Peak 46 Mean 26 Valve area, cm2 44 1.0 with estimates of lumen loss of 0.10 cm2 per year11 and increase in peak gradient of 10 mm Hg per year,12 but there is great variation among individual patients. There is considerable valve area reserve. Symptoms of aortic stenosis do not develop until there has been 60% to 75% loss of valve area to less than 1.0 cm2. As a result of this large reserve and very slow progression, many patients remain asymptomatic for a decade or more, though a murmur is usually heard when the valve area is 1.5 to 2 cm2, a level considered to be mild aortic stenosis. As expected, normalization for body size may be more meaningful, especially for larger or smaller individuals— with severe aortic stenosis defined as a valve area of less than 1.0 cm2 or a body surface area normalized valve area of less than 0.6 cm2/m2. Dr T has a valve area of 0.7 cm2 (0.35 cm2/m2) placing him in the range of severe aortic stenosis. Measurement of Aortic Stenosis Patients with a suspicion of aortic stenosis or with heart failure and exertional syncope will benefit from a resting transthoracic echocardiography, which readily allows for assessment of LV wall thickness (for hypertrophy), cavity size, and regional-global systolic function. In addition, aortic valve morphology (number of leaflets, leaflet thickening, leaflet mobility) can be assessed. Finally, Doppler echocardiography allows for an accurate noninvasive assessment of aortic valve peak and mean gradients, estimation of aortic valve area, and assessment of aortic regurgitation and mitral regurgitation. Using continuous wave Doppler, the peak and mean gradients across the stenotic aortic valve can be measured. The transthoracic echocardiography peak aortic valve gradient is slightly higher than the gradient reported at cardiac catheterization as the transthoracic echocardiography Doppler gradient measures the maximal instantaneous peak gradient between the aorta and the LV, while invasive measurements report the difference between the peak LV pressure and the peak aortic pressure (Figure 1). The mean gradients derived by both methods are similar. If Doppler echocardiography is unable to assess the valve, other options include planimetry using moderately invasive 2- or 3-dimensional transesophageal echocardiography, computed tomography,13 and cardiovascular magnetic resonance.14 All of these methods offer good correlation with transthoracic echocardiography and cardiac catheterization but with additional cost, invasiveness, or radiation exposure. They are infrequently needed. Medical Management of Significant Aortic Stenosis Dr T has been monitored for nearly a decade since his initial diagnosis with minimal change in the peak aortic valve gradient from jama.com 67 97 43 68 0.9 0.7 2003 to 2005 but has experienced marked increase between 2005 and 2008 and again between 2008 and 2009 (Table 1). Progression of aortic stenosis is highly variable, but usually is very slow,11,12 and there is tremendous reserve so that symptoms may not develop for many decades or until 75% of the valve area has been lost. Although overall progression is approximately 0.10 cm2 per year, data suggest that aortic valve calcification is among the strongest predictors of rapid progression.12 Medical therapy to prevent progression or complications of aortic stenosis is limited. Retrospective data initially suggested a benefit of statin therapy15 in slowing progression, but subsequent prospective studies have demonstrated no benefit for aortic stenosis disease progression (velocity gradient or progression to aortic valve replacement).16,17 Prospective studies of statins did demonstrate a decrease in ischemic cardiovascular events,16 and there is frequent coexistant coronary artery disease. Due to this benefit, I prescribe statin therapy for my patients with aortic stenosis, as was done for Dr T. Patients with all types of prosthetic valves should received antibiotic prophylaxis,18 but current American Heart Association and American College of Cardiology (AHA/ACC) prophylaxis recommendations no longer include antibiotic prophylaxis for native valve aortic stenosis (Box 1).18 I advise patients with severe aortic stenosis to stay well hydrated and to avoid hot tubs or baths, steam rooms, and saunas so as to avoid hypotension that may result from peripheral vasodilation with impaired stroke volume augmentation. For asymptomatic patients with preserved LV ejection fraction, follow-up transthoracic echocardiographs to monitor the gradient and LV systolic function is recommended every 3 to 5 years for mild aortic stenosis, every 1 to 2 years for moderate aortic stenosis, every 6 to 12 months for asymptomatic severe aortic stenosis.19,20 Transthoracic echocardiography is performed to monitor both the severity of aortic stenosis and associated aortic regurgitation as well as LV ejection fraction. Dr T has had several transthoracic echocardiographies (Table 1) over the years, demonstrating relatively stable peak gradients until last year; with subsequent rapid peak gradient progression from 67 to 97 mm Hg. All of his transthoracic echocardiographies have demonstrated a preserved LV ejection fraction. Surgical Treatment of Significant Aortic Stenosis Class I indications for aortic valve surgery as recommended by both the ACC/AHA and the European Society of Cardiology and European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines20,21 include symptomatic (heart failure, exertional presyncope or syncope, or exertional angina) patients with severe aortic stenosis (aortic valve area, <1.0 cm2 or <0.6 cm2/m2) and asympJAMA October 9, 2013 Volume 310, Number 14 Downloaded From: http://jama.jamanetwork.com/ by a Beth Israel Deaconess Medical Center User on 09/24/2014 1493 Clinical Review & Education Clinical Crossroads Asymptomatic Aortic Stenosis in the Elderly Box 1. Recommendations for Patients With Valve Replacements Box 2. Recommendations for Surgery Medical therapy Surgery Statins Nonemergency surgery should be performed 4 to 8 weeks after development of symptoms. Endocarditis prophylaxis is not recommended Follow-up Asymptomatic patients with preserved LV ejection fraction Mild aortic stenosis transthoracic echocardiograph every 3 to 5 years Moderate aortic stenosis transthoracic echocardiograph every 1 to 2 years Severe aortic stenosis transthoracic echocardiograph every 6 months to a year Symptomatic patients and asymptomatic patients with depressed LV ejection fraction are referred for coronary angiography and elective surgery Finally, aortic valve surgery is recommended (class IIa) for asymptomatic patients with mild or greater aortic stenosis at the time of coronary artery bypass graft surgery or other heart valve or thoracic aorta surgery (eg, mitral valve surgery). Observation In the absence of symptoms and with preserved left ventricle (LV) systolic function, observation with deferral of surgery has an excellent prognosis, especially if the peak aortic stenosis gradient is less than 80 mm Hg.40 Asymptomatic patients with severe aortic stenosis but depressed LV ejection fraction are also class I surgical candidates.20,21 Table 2. Indications for Aortic Valve Replacement Based on Current Recommendations Indication for Aortic Valve Replacement ACC/AHA Classa Level of Evidenceb ESC/EACTS Classa Level of Evidenceb Symptomatic severe aortic stenosis I B I B Undergoing coronary artery bypass graft surgery I C I C Undergoing surgery on the aorta or other heart valves I C I C a Not due to another cause. And left ventricular systolic dysfunction <0.50c I C I C b Based on the ACC/AHA20 and ESC/EACTs21 guidelines. IIa B IIa C c Abnormal response to exercise IIb C IIa C When the aortic valve is 0.6 cm2, the mean gradient is higher than 60 mm Hg, and peak velocity is less than 5 m/s indicates that expected operative mortality is less than 1.0%. High likelihood of rapid progression IIb C d Peak velocity is greater than 5.5 m/s or progression is greater than 0.3 m/s per year. Severe aortic stenosis Moderate aortic stenosis undergoing coronary artery bypass graft surgery, surgery on the aorta, or surgery on the other heart valve Abbreviations: ACC/AHA, American College of Cardiology and American Heart Association; ESC/EACTS, European Society of Cardiology and European Association for Cardio-Thoracic Surgery. Asymptomatic aortic stenosis Severe Extreme severe b IIb C tomatic patients with depressed ejection fraction (<50%; Box 2). Of the 3 cardinal symptoms, heart failure is the most ominous with survival of less than a year after heart failure symptoms without valve replacement.22 For patients who present with exertional syncope, survival is less than 2 years after development of syncope without valve replacement (Table 2, Figure 3). Dr T is largely asymptomatic except for a single episode of dyspnea while walking up a steep incline. He reports being able to perform his usual daily activities, including regular use of elliptical machines without symptoms. Some patients will subconsciously restrict their activity to avoid symptoms. Thus, while they have no symptoms, it is because they have curtailed their activities, often ascribing their diminished activity level to “advancing age.” For patients with equivocal symptoms like Dr T, I often perform a carefully monitored exercise stress test. An abnormal response (found in a third of seemingly asymptomatic patients) includes the development of symptoms or a decrease in blood pressure and defines a high-risk group that is likely to need valve replacement within a year.23 Dr T’s stress test showed a drop in blood pressure and ischemic ST-wave depression suggesting that he is at high risk of mortality (Box 3). Conventional aortic stenosis treatment options include surgical valve replacement with a mechanical or bioprosthetic valve, a 1494 IIa d C cadaver aortic valve, and the Ross procedure (Table 3). A new option for high-risk patients is transcutaneous aortic valve implant.25-27 Both mechanical and bioprosthetic aortic valves give a similar hemodynamic profile. All prosthetic valves increase the risk of endocarditis, so antibiotic prophylaxis is recommended. Mechanical aortic valves are more durable but have higher thrombogenicity, requiring lifelong warfarin (typical target international normalized ratio, 2.0-3.0). Oral warfarin alternatives including dabigatran, rivaroxaban, and apixaban have not been fully assessed for mechanical valves, but adverse events have been reported for dabigatran.28 A prospective trial comparing dabigatran with warfarin in patients with prosthetic valves was prematurely stopped due to increased stroke, myocardial infarction, and mechanical valve thrombi in the dabigatran group.29 Bioprosthetic aortic valves do not require warfarin, but they are less durable,30 especially in younger patients and those with renal dysfunction, failing due to fibrosis or calcification with resultant stenosis, or regurgitation, or both. The longevity of bioprosthetic valves is inversely related to the patient’s age, with a longevity of 1 to 2 decades for patients older than 70 years vs 5 to 10 years for patients younger than 50 years. Thus, otherwise healthy patients younger than 60 years or patients who need long-term warfarin for another condition JAMA October 9, 2013 Volume 310, Number 14 Downloaded From: http://jama.jamanetwork.com/ by a Beth Israel Deaconess Medical Center User on 09/24/2014 jama.com Asymptomatic Aortic Stenosis in the Elderly (eg, atrial fibrillation) generally receive mechanical valves, while for those older than 70 years old, such as Dr T, bioprosthetic valves are preferred. These bioprostheses will provide a good hemodynamic result with 15- to 20-year longevity. In-hospital mortality among patients requiring isolated aortic valve surgery is 2% to 5% and increases to 5% to 10% if coronary artery bypass graft surgery is also needed.31 Excellent results are obtained even among patients like Dr T who are older than 80 years.32 Risk factors for in-hospital mortality include hypertension, diabetes, depressed LV ejection fraction, emergency surgery, and prior cardiac surgery.31-33 From these data, Dr T has a predicted inhospital mortality of approximately 3% with excellent long-term survival.31-33 For patients who survive without morbidity, the longterm prognosis of isolated aortic valve replacement for aortic stenosis is excellent and approximates the normal population.34 Adverse long-term risk factors include stroke, smoking, diabetes, and renal failure.32,35 Were Dr T to have numerous comorbidities so as to be at very high risk of cardiac surgery, consideration of transcutaneous aortic valve implant would be considered. In the United States, the Edwards Sapien and Medtronic CoreValve options have been the most widely studied. Current data are promising in very high-risk patients with regards to short-term morbidity and mortality with benefit at 2 years for mortality (vs medical therapy).25-27 Major advantages of the transcutaneous aortic valve implant approach are the rapid patient recovery but with an increased risk of vascular complications, heart block, and stroke. Postprocedure aortic regurgitation appears to be a predictor for adverse outcomes.35 Currently, the Edwards Sapien valve is approved by the US Food and Drug Administration for use in patients with severe symptomatic calcified aortic stenosis at high risk of operative morbidity and mortality.36 Data suggest similar 30-day and 1-year mortality and major morbidity for the Edwards Sapien and Medtronic CoreValve systems.37 Because the presence of angina may be related to aortic stenosis or coexistant coronary artery disease and because patients with aortic stenosis are often older with typical risk factors for coronary artery disease, screening coronary angiography is recommended for most adult patients prior to aortic valve surgery.20,21 Data suggest a potential role for coronary computed tomography as a screening test to exclude obstructive coronary artery disease38 in middleaged patients. If any stenoses are suggested, a coronary angiogram is performed. Clinical Crossroads Clinical Review & Education Figure 3. Algorithm for Management of Severe Aortic Stenosis Follow-up every 6-12 mo Severe aortic valve stenosis Valve area < 1.0 cm2 Indexed valve area < 0.6 cm2/m2 BSA Yes Symptoms present or needs other heart or aortic surgery No Uncertain Symptoms or Decrease in BP Exercise test No symptoms or Increase in BP Yes LVEF < 50% ? No Aortic valve replacement Adapted from Bonow et al20 and Vahanian et al.21 BP indicates blood pressure and LVEF, left ventricular ejection fraction Box 3. American Heart Association Recommendationsa I. Evidence or general agreement that a given procedure or treatment is useful and effective. II. Conflicting evidence or a divergence of opinion about the usefulness or efficacy of a procedure or treatment a. Evidence favors an interventions usefulness b. Evidence regarding an interventions utility is less well established III. Evidence, general agreement, or both that the procedure or treatment is not useful or effective and in some cases may be harmful a Based on Gibbons et al.24 Table 3. Treatment Options for Aortic Stenosis Option Target Group Advantages All Decrease in ischemic cardiovascular events Cadaver Younger adults No need for warfarin; moderate longevity; can be used for women of child-bearing age Biological >65 y No need for warfarin; 15-20 year longevity Medical treatment Statin Surgery options Valve Recommendations for Dr T Dr T is relatively asymptomatic but has severe aortic stenosis and preserved LV ejection fraction. Although he reports regular exercise on an elliptical, I am particularly concerned by the abnormal hypotensive response on stress testing at a low workload, with accompanying ischemic electrocardiographic changes. Based on this, he has a class IIa recommendation for surgical intervention (Table 2).20,21 I recommend that he undergo a coronary angiogram to determine the presence of coexistant coronary artery disease (there is no need to cross the aortic valve to confirm the gradient or to perform left ventriculography) followed by elective aortic valve surgery with a bioprosthetic valve (coronary artery bypass may be jama.com Mechanical <65 y Needs warfarin Ross procedurea <40 y No need for warfarin; moderate longevity TAVI >65 y Shorter surgical recovery Abbreviation: TAVI, transcutaneous aortic valve implant. a Ross procedure is an operation in which the patient’s native pulmonic valve is moved to the aortic position and a cadaver valve is placed in the pulmonic position. JAMA October 9, 2013 Volume 310, Number 14 Downloaded From: http://jama.jamanetwork.com/ by a Beth Israel Deaconess Medical Center User on 09/24/2014 1495 Clinical Review & Education Clinical Crossroads Asymptomatic Aortic Stenosis in the Elderly needed as well depending on the results of the angiogram). A bioprosthesis will provide good valve longevity without the need for long-term warfarin. The procedure should be performed in the next 4 to 8 weeks. Follow-up With Dr T Based on the recommendations of Dr Manning, Dr T decided to undergo surgery. In April 2009, 1 month after the conference, he underwent coronary angiography. The aortic valve was not crossed with a catheter. Angiography demonstrated 90% stenoses of the first and second obtuse marginal arteries. Three weeks later, he underwent uncomplicated aortic valve replacement with a bioprosthetic valve and 2-vessel bypass. He was discharged on postoperative day 6 with home visiting nurse and physical therapy supports. In 2013, Dr T has just turned 90 years-old and is doing quite well. He remains happy with his decision to proceed with surgery. He continues to be very physically active, exercising on the elliptical machine every other day without any shortness of breath or chest pain. He is currently taking 81 mg of aspirin, 2.5 mg of lisinopril, and 20 mg of simvastatin daily and 100 mg of metoprolol succinate twice a day. He is grateful to Dr Manning for helping him make the decision to proceed with surgery. Questions and Discussion QUESTION He has restless leg syndrome that can be caused by iron deficiency. Do you think he is having intravascular red cell lysis from the deformed valve? DR MANNING Although reported, it is not common to have red cell lysis with native valve aortic stenosis. This condition is more common with prosthetic valve dysfunction either due to a stenosis or a perivalvular leak. Aortic stenosis has been associated with both angiodysplasia and clotting abnormalities (impaired platelet function and decreased levels of von Willebrand factors).39 QUESTION Why is it that he can do the elliptical but not walk up the hill? DR MANNING I suspect he has modified his activity. We know that his blood pressure fell at a treadmill speed of only 1.7 miles per hour and at a 10° elevation. That is not a very high intensity. We also know that his rate-pressure-product (peak heart rate × peak systolic blood pressure) only reached 12 000. Even though he is using the elliptical, I suspect it is not with great intensity. Patients with aortic stenosis will often have shortness of breath with exertion and will reduce their effort. They say, “Oh, I’m just getting a little older,” or “I now prefer doubles to singles tennis.” They are simply adapting to the inability to increase stroke volume and cardiac output. QUESTION How do you evaluate patients after surgery? Do they need yearly echoes? DR MANNING I usually obtain 1 transthoracic echocardiograph in the first few months after surgery to document the baseline gradient and any potential valvular regurgitation. Presuming the patient is stable and asymptomatic, unless there is a change in examination or symptoms, I will not obtain another one for 4 to 5 years.19 Due to the potential for valve failure with bioprosthetic valves, beginning at 10 years after implantation,30 I usually obtain a transthoracic echocardiograph every 3 years.19 ARTICLE INFORMATION REFERENCES Conflict of Interest Disclosures: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and reports that he has received a research grant from Philips Medical Systems. Several years after this presentation, Dr Manning became a site coinvestigator for the Medtronic CoreValve System and has received travel reimbursement for an investigator meeting. 1. Nkomo VT, Gardin JM, Skelton TN, Gottdiener JS, Scott CG, Enriquez-Sarano M. Burden of valvular heart diseases: a population-based study. Lancet. 2006;368(9540):1005-1011. The conference on which this article is based took place at the Medicine Grand Rounds at Beth Israel Deaconess Medical Center, Boston, Massachusetts, on Thursday, March 12, 2009. 3. Rajamannan NM, Subramaniam M, Rickard D, et al. Human aortic valve calcification is associated with an osteoblast phenotype. Circulation. 2003;107(17):2181-2184. Additional Contributions: We thank the patient for sharing his story and for providing permission to publish it. 4. Stewart BF, Siscovick D, Lind BK, et al. Clinical factors associated with calcific aortic valve disease: Cardiovascular Health Study. J Am Coll Cardiol. 1997;29(3):630-634. Clinical Crossroads at Beth Israel Deaconess Medical Center is produced and edited by Risa B. Burns, MD, series editor; Jon Crocker, MD, Howard Libman, MD, Eileen E. Reynolds, MD, Amy N. Ship, MD, Gerald Smetana, MD, and Anjala V. Tess, MD. 1496 QUESTION What is the best way to get Dr T back up on his feet quickly after surgery? DR MANNING Prior to surgery, Dr T should stay active to avoid deconditioning by walking and using his elliptical machine but should not increase his exercise intensity. Preoperative dental assessment is important to reduce the risk of subsequent endocarditis. Hospitalization would likely be for 5 to 7 days followed by 1 to 2 weeks of more intense rehabilitation. Near complete recovery is within 2 months, although I advise very active patients after sternotomy to avoid vigorous upper body exercises (eg, golf, tennis, bowling) for 3 to 6 months to allow for full sternal healing. Walking is an excellent form of postsurgery exercise. 2. NHLBI Works Group Calcific Aortic Stenosis Executive Summary. National Heart, Lung, and Blood Institute. http://www.nhlbi.nih.gov/meetings /workshops/cas.htm. Updated March 2010. Accessed August 28, 2013. 5. Dweck MR, Jones C, Joshi NV, et al. Assessment of valvular calcification and inflammation by positron emission tomography in patients with aortic stenosis. Circulation. 2012;125(1):76-86. 6. Lancellotti P, Moonen M, Magne J, et al. Prognostic effect of long-axis left ventricular dysfunction and B-type natriuretic peptide levels in asymptomatic aortic stenosis. Am J Cardiol. 2010;105(3):383-388. 7. Bauer F, Mghaieth F, Dervaux N, et al. Preoperative tissue Doppler imaging differentiates beneficial from detrimental left ventricular hypertrophy in patients with surgical aortic stenosis: a postoperative morbidity study. Heart. 2008;94(11):1440-1445. 8. Azevedo CF, Nigri M, Higuchi ML, et al. Prognostic significance of myocardial fibrosis quantification by histopathology and magnetic resonance imaging in patients with severe aortic valve disease. J Am Coll Cardiol. 2010;56(4): 278-287. 9. Kupari M, Turto H, Lommi J. 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