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InternalMed_Harrison. Death in patients with severe AS occurs most commonly in the seventh and eighth decades. Based on data obtained at postmortem examination in patients before surgical treatment became widely available, the average time to death after the onset of various symptoms was as follows: angina pectoris, 3 years; syncope, 3 years; dyspnea, 2 years; congestive heart failure, 1.5–2 years. Moreover, in >80% of patients who died with AS, symptoms had existed for <4 years. Among adults dying with valvular AS, sudden death, which presumably resulted from an arrhythmia, occurred in 10–20%; however, most sudden deaths occurred in patients who had previously been symptomatic. Sudden death as the first manifestation of severe AS is very uncommon (<1% per year) in asymptomatic adult patients. Calcific AS is a progressive disease, with an annual reduction in valve area averaging 0.1 cm2 and annual increases in the peak jet velocity and mean valve gradient averaging 0.3 meters/s and 7 mmHg, respectively


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InternalMed_Harrison. a progressive disease, with an annual reduction in valve area averaging 0.1 cm2 and annual increases in the peak jet velocity and mean valve gradient averaging 0.3 meters/s and 7 mmHg, respectively (Table 283-2).


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TREATMEnT aortic StenoSiS (fig. 283-2)

InternalMed_Harrison. TREATMEnT aortic StenoSiS (fig. 283-2)


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InternalMed_Harrison. In patients with severe AS (valve area <1 cm2), strenuous physical activity and competitive sports should be avoided, even in the asymptomatic stage. Care must be taken to avoid dehydration and hypovolemia to protect against a significant reduction in CO. Medications used for the treatment of hypertension or CAD, including beta blockers and angiotensin-converting enzyme (ACE) inhibitors, are generally safe for asymptomatic patients with preserved LV systolic function. Nitroglycerin is helpful in relieving angina pectoris in patients with CAD. Retrospective studies have shown that patients with degenerative calcific AS who receive HMG-CoA reductase inhibitors (“statins”) exhibit slower progression of leaflet calcification and aortic valve area reduction than those who do not. However, randomized prospective studies with either high-dose atorvastatin or combination simvastatin/ezetimibe have failed to show a measurable effect on valve-related outcomes. The use of statin medications


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InternalMed_Harrison. randomized prospective studies with either high-dose atorvastatin or combination simvastatin/ezetimibe have failed to show a measurable effect on valve-related outcomes. The use of statin medications should continue to be driven by considerations regarding primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) events. ACE inhibitors have not been studied prospectively for AS-related outcomes. The need for endocarditis prophylaxis is restricted to AS patients with a prior history of endocarditis.


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InternalMed_Harrison. Asymptomatic patients with calcific AS and severe obstruction should be followed carefully for the development of symptoms and by serial echocardiograms for evidence of deteriorating LV function. Operation is indicated in patients with severe AS (valve aData are for the first two quarters of calendar year 2013, during which 1004 sites reported a total of 135,666 procedures. Data are available from the Society of Thoracic Surgeons at http://www.sts.org/sites/default/files/documents/2013_3rdHarvestExecutiveSummary.pdf. Abbreviations: AVR, aortic valve replacement; CAB, coronary artery bypass; MVR, mitral valve replacement.


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InternalMed_Harrison. area <1 cm2 or 0.6 cm2/m2 body surface area) who are symptomatic, those who exhibit LV systolic dysfunction (EF <50%), and those with BAV disease and an aneurysmal root or ascending aorta (maximal dimension >5.5 cm). Operation for aneurysm disease is recommended at smaller aortic diameters (4.5–5.0 cm) for patients with a family history of an aortic catastrophe and for patients who exhibit rapid aneurysm growth (>0.5 cm/year). Patients with asymptomatic moderate or severe AS who are referred for coronary artery bypass grafting surgery should also have AVR. In patients without heart failure, the operative risk of AVR (including patients with AS or AR) is approximately 2% (Table 283-2) but increases as a function of age and the need for concomitant aortic surgery or coronary revascularization with bypass grafting. The indications for AVR in the asymptomatic patient have been the subject of intense debate over the past 5 years, as surgical outcomes in selected patients have continued to


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InternalMed_Harrison. with bypass grafting. The indications for AVR in the asymptomatic patient have been the subject of intense debate over the past 5 years, as surgical outcomes in selected patients have continued to improve. Relative indications for which surgery can be considered include an abnormal response to treadmill exercise; rapid progression of AS, especially when urgent access to medical care might be compromised; very severe AS, defined by an aortic valve jet velocity >5 meters/s or mean gradient >60 mmHg and low operative risk; and excessive LV hypertrophy in the absence of systemic hypertension. Exercise testing can be safely performed in the asymptomatic patient, as many as one-third of whom will show signs of functional impairment.


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InternalMed_Harrison. Operation should be carried out promptly after symptom onset. In patients with low-flow, low-gradient severe AS with reduced LVEF, the perioperative mortality risk is high (15–20%), and evidence of myocardial disease may persist even when the operation is technically successful. Long-term postoperative survival correlates with preoperative LV function. Nonetheless, in view of the even worse prognosis of such patients when they are treated medically, there is usually little choice but to advise valve replacement, especially in patients in whom contractile reserve can be demonstrated by dobutamine stress echocardiography (defined by a ≥20% increase in stroke volume after dobutamine challenge). Patients in this high surgical risk group may benefit from transcatheter aortic valve replacement (TAVR, see below). The treatment of patients with low-flow, low-gradient severe AS with normal LVEF is also difficult. Outcomes appear to be better with surgery compared with conservative medical care


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InternalMed_Harrison. see below). The treatment of patients with low-flow, low-gradient severe AS with normal LVEF is also difficult. Outcomes appear to be better with surgery compared with conservative medical care for symptomatic patients with this type of “paradoxical” low-flow AS, but more research is needed to guide therapeutic decision-making. In patients in whom severe AS and CAD coexist, relief of the AS and revascularization may sometimes result in striking clinical and hemodynamic improvement (Table 283-2).


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InternalMed_Harrison. Because many patients with calcific AS are elderly, particular attention must be directed to the adequacy of hepatic, renal, and pulmonary function before AVR is recommended. Age alone is not a contraindication to AVR for AS. The perioperative mortality rate depends to a substantial extent on the patient’s preoperative clinical and hemodynamic state. Treatment decisions for AS patients who are not at low operative risk should be made by a multidisciplinary heart team with representation from general cardiology, interventional cardiology, imaging, cardiac surgery, and other allied specialties as needed, including geriatrics. The 10-year survival rate of older adult patients with AVR is approximately 60%. Approximately 30% of bioprosthetic valves evidence primary valve failure in 10 years, requiring re-replacement, and an approximately equal percentage of patients with mechanical prostheses develop significant hemorrhagic complications as a consequence of treatment with vitamin K


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InternalMed_Harrison. requiring re-replacement, and an approximately equal percentage of patients with mechanical prostheses develop significant hemorrhagic complications as a consequence of treatment with vitamin K antagonists. Homograft AVR is usually reserved for patients with aortic valve endocarditis.


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InternalMed_Harrison. The Ross procedure involves replacement of the diseased aortic valve with the autologous pulmonic valve and implantation of a homograft in the native pulmonic position. Its use has declined considerably in the United States because of the technical complexity of the procedure and the incidence of late postoperative aortic root dilation and autograft failure with AR. There is also a low incidence of pulmonary homograft stenosis. Vmax 3 m/s –3.9 m/s ˛Pmean 20–39 mmHg Severe AS Vmax °4 m/s ˛Pmean °40 mmHg AVR (I) AVR (IIa) AVR (IIb) Vmax °5 m/s ˛Pmean °60 mmHg low surgical risk ˛Vmax >0.3 m/s/y low surgical risk Abnormal ETT Asymptomatic (stage C) LVEF <50% (stage C2) Other cardiac surgery Symptomatic (stage D1)


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InternalMed_Harrison. FIGURE 283-2 Management strategy for patients with aortic stenosis. Preoperative coronary angiography should be performed routinely as determined by age, symptoms, and coronary risk factors. Cardiac catheterization and angiography may also be helpful when there is a discrepancy between clinical and noninvasive findings. Patients who do not meet criteria for intervention should be monitored periodically with clinical and echocardiographic follow-up. The class designations refer to the American College of Cardiology/American Heart Association methodology for treatment recommendations. Class I recommendations should be performed or are indicated; Class IIa recommendations are considered reasonable to perform; Class IIb recommendations may be considered. The stages refer to the stages of progression of the disease. At disease stage A, risk factors are present for the development of valve dysfunction; stage B refers to progressive, mild-moderate, asymptomatic valve disease; stage C disease


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InternalMed_Harrison. of the disease. At disease stage A, risk factors are present for the development of valve dysfunction; stage B refers to progressive, mild-moderate, asymptomatic valve disease; stage C disease is severe in nature but clinically asymptomatic; stage C1 characterizes asymptomatic patients with severe valve disease but compensated ventricular function; stage C2 refers to asymptomatic, severe disease with ventricular decompensation; stage D refers to severe, symptomatic valve disease. With aortic stenosis, stage D1 refers to symptomatic patients with severe aortic stenosis and a high valve gradient (>40 mmHg mean gradient); stage D2 comprises patients with symptomatic, severe, low-flow, low-gradient aortic stenosis and low left ventricular ejection fraction; and stage D3 characterizes patients with symptomatic, severe, low-flow, low-gradient aortic stenosis and preserved left ventricular ejection fraction (paradoxical, low-flow, low-gradient severe aortic stenosis). AS, aortic stenosis;


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InternalMed_Harrison. with symptomatic, severe, low-flow, low-gradient aortic stenosis and preserved left ventricular ejection fraction (paradoxical, low-flow, low-gradient severe aortic stenosis). AS, aortic stenosis; AVA; aortic valve area; AVR, aortic valve replacement by either surgical or transcatheter approach; BP, blood pressure; DSE, dobutamine stress echocardiography; ETT, exercise treadmill test; LVEF, left ventricular ejection fraction; ΔP , mean pressure gradient; and V , maximum velocity. (Adapted from RA Nishimura et al: 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease. J Am Coll Cardiol doi: 10.1016/j.jacc.2014.02.536, 2014, with permission.)


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InternalMed_Harrison. This procedure is preferable to operation in many children and young adults with congenital, noncalcific AS (Chap. 282). It is not commonly used as definitive therapy in adults with severe calcific AS because of a very high restenosis rate (80% within 1 year) and the risk of procedural complications, but on occasion, it has been used successfully as a “bridge to operation” in patients with severe LV dysfunction and shock who are too ill to tolerate surgery. It is performed routinely as part of the TAVR procedure (see below). TAVR for treatment of AS has been performed in more than 50,000 prohibitiveor high-surgical-risk adult patients worldwide using one of two available systems, a balloon-expandable valve and a self-expanding valve, both of which incorporate a pericardial prosthesis (Fig. 283-3). More than 250 U.S. centers now offer this procedure.


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InternalMed_Harrison. TAVR is most frequently performed via the transfemoral route, although trans-LV apical, subclavian, carotid, and ascending aortic routes have been used. Aortic balloon valvuloplasty under rapid RV pacing is performed as a first step to create an orifice of sufficient size for the prosthesis. Procedural success rates exceed 90%. Among elderly patients with severe AS who are considered inoperable (i.e., prohibitive surgical risk), 1and 2-year survival rates are significantly higher with TAVR compared with medical therapy (including PABV) (Fig. 283-4). Oneand 2-year survival rates are essentially equal for high-surgical-risk patients treated with TAVR or surgical AVR (SAVR) (Fig. 283-5). TAVR is associated with an early hazard for stroke and a higher incidence of postprocedural, paravalvular AR, a risk factor for mortality over the next 2 years. Postprocedural heart block requiring permanent pacemaker therapy is observed significantly more frequently with the self-expanding valve. Valve


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InternalMed_Harrison. AR, a risk factor for mortality over the next 2 years. Postprocedural heart block requiring permanent pacemaker therapy is observed significantly more frequently with the self-expanding valve. Valve performance characteristics are excellent. Overall outcomes with this transformative technology have been very favorable and have allowed the extension of AVR to groups of patients previously considered at high or prohibitive risk for conventional surgery. Nevertheless, some patients are not candidates for this procedure because their comorbidity profile, including an assessment of frailty, would make its undertaking inappropriate. The heart team is specifically charged with making challenging decisions of this nature. The use of these devices for the treatment of patients at intermediate operative risk and for those with structural deterioration of bioprosthetic aortic and mitral valves (“valve-in-valve”), as an alternative to reoperative valve replacement, is under active study.


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InternalMed_Harrison. FIGURE 283-3 Balloon-expandable (A) and self-expanding (B) valves for transcatheter aortic valve replacement (TAVR). B, inflated balloon; N, nose cone; V, valve. (Part A, courtesy of Edwards Lifesciences, Irvine, CA; with permission. NovaFlex+ is a trademark of Edwards Lifesciences Corporation. Part B, © Medtronic, Inc. 2015. Medtronic CoreValve Transcatheter Aortic Valve. CoreValve is a registered trademark of Medtronic, Inc.) Hazard ratio, 0.56 (95% CI, 0.43–0.73) P<0.001 (Table 283-1) AR may be caused by primary valve disease or by primary aortic root disease. Primary Valve Disease Rheumatic disease results in thickening, deformity, and shortening of the individual aortic valve cusps, changes that prevent their proper opening during systole and closure during diastole. A rheumatic origin is much less common in patients with isolated AR who do not have associated rheumatic mitral valve disease. Patients with congenital BAV disease may develop predominant AR,


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InternalMed_Harrison. Death from any Cause, Intention-to-Treat Population 68.0 Standard therapy 43.3 TAVR 0 10 20 30Death from any cause (%)40 50 60 Surgery TAVR Hazard ratio, 0.90 (95% CI, 0.71–1.15) P = 0.41 No. at Risk


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InternalMed_Harrison. No. at Risk FIGURE 283-4 Twenty-four-month outcomes following transcatheter aortic valve replacement (TAVR) for inoperable patients in the PARTNER I trial (cohort B). CI, confidence interval. (Adapted from RR Makkar et al: N Engl J Med 366:1696, 2012; with permission.) and approximately 20% of patients will require aortic valve surgery between 10 and 40 years of age. Congenital fenestrations of the aortic valve occasionally produce mild AR. Membranous subaortic stenosis often leads to thickening and scarring of the aortic valve leaflets with secondary AR. Prolapse of an aortic cusp, resulting in progressive chronic AR, occurs in approximately 15% of patients with ventricular septal defect (Chap. 282) but may also occur as an isolated phenomenon or as a consequence of myxomatous degeneration sometimes associated with mitral and/or tricuspid valve involvement.


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InternalMed_Harrison. AR may result from infective endocarditis, which can develop on a valve previously affected by rheumatic disease, a congenitally deformed valve, or on a normal aortic valve, and may lead to perforation or erosion of one or more leaflets. The aortic valve leaflets may become scarred and retracted during the course of syphilis or ankylosing spondylitis and contribute further to the AR that derives primarily from the associated root disease. Although traumatic rupture or avulsion of an aortic cusp is an uncommon cause of acute AR, it represents the most frequent serious lesion in patients surviving nonpenetrating cardiac injuries. The coexistence of hemodynamically significant AS with AR usually excludes all the rarer forms of AR because it occurs almost exclusively in patients with rheumatic or congenital AR. In patients with AR due to primary valvular disease, dilation of the aortic annulus may occur secondarily and lead to worsening regurgitation.


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InternalMed_Harrison. Primary Aortic Root Disease AR also may be due entirely to marked aortic annular dilation, i.e., aortic root disease, without primary involvement of the valve leaflets; widening of the aortic annulus and separation of the aortic leaflets are responsible for the AR (Chap. 301). Medial degeneration of the ascending aorta, which may or may not be associated with other manifestations of Marfan’s syndrome; idiopathic dilation of the aorta; annuloaortic ectasia; osteogenesis imperfecta; and severe, chronic hypertension may all widen the aortic annulus and lead to progressive AR. Occasionally AR is caused by retrograde dissection of the aorta involving the aortic annulus. Syphilis and ankylosing spondylitis, both of which may affect the aortic leaflets, may also be associated with cellular infiltration and scarring of the media of the thoracic aorta, leading to aortic dilation, aneurysm formation, and severe regurgitation. In syphilis of the aorta (Chap. 206), now a very rare condition, the


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InternalMed_Harrison. and scarring of the media of the thoracic aorta, leading to aortic dilation, aneurysm formation, and severe regurgitation. In syphilis of the aorta (Chap. 206), now a very rare condition, the involvement of the intima may narrow the coronary ostia, which in turn may be responsible for myocardial ischemia.


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InternalMed_Harrison. The total stroke volume ejected by the LV (i.e., the sum of the effective forward stroke volume and the volume of blood that regurgitates back into the LV) is increased in patients with AR. In patients with severe AR, the volume of regurgitant flow may equal the effective forward stroke volume. In contrast to MR, in which a portion of the LV stroke volume is delivered into the low-pressure LA, in AR the entire LV stroke volume is ejected into a high-pressure zone, the aorta. An increase in the LV end-diastolic volume (increased preload) constitutes the major hemodynamic compensation for AR. The dilation and eccentric hypertrophy of the LV allow this chamber to eject a larger stroke volume without requiring any increase in the relative shortening of each myofibril. Therefore, severe AR may occur with a normal effective forward stroke volume and a normal LVEF (total [forward plus regurgitant] stroke volume/end-diastolic volume), together with an elevated LV end-diastolic pressure and


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InternalMed_Harrison. occur with a normal effective forward stroke volume and a normal LVEF (total [forward plus regurgitant] stroke volume/end-diastolic volume), together with an elevated LV end-diastolic pressure and volume. However, through the operation of Laplace’s law, LV dilation increases the LV systolic tension required to develop any given level of systolic pressure. Chronic AR is, thus, a state in which LV preload and afterload are both increased. Ultimately, these adaptive measures fail. As LV function deteriorates, the end-diastolic volume rises further and the forward stroke volume and EF decline. Deterioration of LV function often precedes the development of symptoms. Considerable thickening of the LV wall also occurs with chronic AR, and at autopsy, the hearts of these patients may be among the largest encountered, sometimes weighing >1000 g.


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InternalMed_Harrison. The reverse pressure gradient from aorta to LV, which drives the AR flow, falls progressively during diastole, accounting for the decrescendo nature of the diastolic murmur. Equilibration between aortic and LV 1535 pressures may occur toward the end of diastole in patients with chronic severe AR, particularly when the heart rate is slow. In patients with acute severe AR, the LV is unprepared for the regurgitant volume load. LV compliance is normal or reduced, and LV diastolic pressures rise rapidly, occasionally to levels >40 mmHg. The LV pressure may exceed the LA pressure toward the end of diastole, and this reversed pressure gradient closes the mitral valve prematurely.


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InternalMed_Harrison. In patients with chronic severe AR, the effective forward CO usually is normal or only slightly reduced at rest, but often it fails to rise nor mally during exertion. An early sign of LV dysfunction is a reduction in the EF. In advanced stages, there may be considerable elevation of the LA, PA wedge, PA, and RV pressures and lowering of the forward CO at rest. Myocardial ischemia may occur in patients with AR because myocardial oxygen requirements are elevated by LV dilation, hypertrophy, and elevated LV systolic tension, and coronary blood flow may be compromised. A large fraction of coronary blood flow occurs during diastole, when arterial pressure is low, thereby reducing coronary perfusion or driving pressure. This combination of increased oxygen demand and reduced supply may cause myocardial ischemia, particularly of the subendocardium, even in the absence of epicardial CAD.


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InternalMed_Harrison. Approximately three-fourths of patients with pure or predominant valvular AR are men; women predominate among patients with primary valvular AR who have associated rheumatic mitral valve disease. A history compatible with infective endocarditis may sometimes be elicited from patients with rheumatic or congenital involvement of the aortic valve, and the infection often precipitates or seriously aggravates preexisting symptoms. In patients with acute severe AR, as may occur in infective endocarditis, aortic dissection, or trauma, the LV cannot dilate sufficiently to maintain stroke volume, and LV diastolic pressure rises rapidly with associated marked elevations of LA and PA wedge pressures. Pulmonary edema and/or cardiogenic shock may develop rapidly.


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InternalMed_Harrison. Chronic severe AR may have a long latent period, and patients may remain relatively asymptomatic for as long as 10–15 years. However, uncomfortable awareness of the heartbeat, especially on lying down, may be an early complaint. Sinus tachycardia, during exertion or with emotion, or premature ventricular contractions may produce particularly uncomfortable palpitations as well as head pounding. These complaints may persist for many years before the development of exertional dyspnea, usually the first symptom of diminished cardiac reserve. The dyspnea is followed by orthopnea, paroxysmal nocturnal dyspnea, and excessive diaphoresis. Anginal chest pain even in the absence of CAD may occur in patients with severe AR, even in younger patients. Anginal pain may develop at rest as well as during exertion. Nocturnal angina may be a particularly troublesome symptom, and it may be accompanied by marked diaphoresis. The anginal episodes can be prolonged and often do not respond satisfactorily to


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InternalMed_Harrison. exertion. Nocturnal angina may be a particularly troublesome symptom, and it may be accompanied by marked diaphoresis. The anginal episodes can be prolonged and often do not respond satisfactorily to sublingual nitroglycerin. Systemic fluid accumulation, including congestive hepatomegaly and ankle edema, may develop late in the course of the disease.


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InternalMed_Harrison. In chronic severe AR, the jarring of the entire body and the bobbing motion of the head with each systole can be appreciated, and the abrupt distention and collapse of the larger arteries are easily visible. The examination should be directed toward the detection of conditions predisposing to AR, such as bicuspid valve, endocarditis, Marfan’s syndrome, and ankylosing spondylitis.


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InternalMed_Harrison. Arterial Pulse A rapidly rising “water-hammer” pulse, which collapses suddenly as arterial pressure falls rapidly during late systole and diastole (Corrigan’s pulse), and capillary pulsations, an alternate flushing and paling of the skin at the root of the nail while pressure is applied to the tip of the nail (Quincke’s pulse), are characteristic 1536 of chronic severe AR. A booming “pistol-shot” sound can be heard over the femoral arteries (Traube’s sign), and a to-and-fro murmur (Duroziez’s sign) is audible if the femoral artery is lightly compressed with a stethoscope. The arterial pulse pressure is widened as a result of both systolic hypertension and a lowering of the diastolic pressure. The measurement of arterial diastolic pressure with a sphygmomanometer may be complicated by the fact that systolic sounds are frequently heard with the cuff completely deflated. However, the level of cuff pressure at the time of muffling of the Korotkoff sounds (phase IV) generally corresponds


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InternalMed_Harrison. fact that systolic sounds are frequently heard with the cuff completely deflated. However, the level of cuff pressure at the time of muffling of the Korotkoff sounds (phase IV) generally corresponds fairly closely to the true intraarterial diastolic pressure. As the disease progresses and the LV end-diastolic pressure rises, the arterial diastolic pressure may actually rise as well, because the aortic diastolic pressure cannot fall below the LV end-diastolic pressure. For the same reason, acute severe AR may also be accompanied by only a slight widening of the pulse pressure. Such patients are invariably tachycardic as the heart rate increases in an attempt to preserve the CO.


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InternalMed_Harrison. Palpation In patients with chronic severe AR, the LV impulse is heaving and displaced laterally and inferiorly. The systolic expansion and diastolic retraction of the apex are prominent. A diastolic thrill may be palpable along the left sternal border in thin-chested individuals, and a prominent systolic thrill may be palpable in the suprasternal notch and transmitted upward along the carotid arteries. This systolic thrill and the accompanying murmur do not necessarily signify the coexistence of AS. In some patients with AR or with combined AS and AR, the carotid arterial pulse may be bisferiens, i.e., with two systolic waves separated by a trough (see Fig. 267-2D).


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InternalMed_Harrison. Auscultation In patients with severe AR, the aortic valve closure sound (A2) is usually absent. A systolic ejection sound is audible in patients with BAV disease, and occasionally an S4 also may be heard. The murmur of chronic AR is typically a high-pitched, blowing, decrescendo diastolic murmur, heard best in the third intercostal space along the left sternal border (see Fig. 267-5B). In patients with mild AR, this murmur is brief, but as the severity increases, it generally becomes louder and longer, indeed holodiastolic. When the murmur is soft, it can be heard best with the diaphragm of the stethoscope and with the patient sitting up, leaning forward, and with the breath held in forced expiration. In patients in whom the AR is caused by primary valvular disease, the diastolic murmur is usually louder along the left than the right sternal border. However, when the murmur is heard best along the right sternal border, it suggests that the AR is caused by aneurysmal dilation of the


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InternalMed_Harrison. is usually louder along the left than the right sternal border. However, when the murmur is heard best along the right sternal border, it suggests that the AR is caused by aneurysmal dilation of the aortic root. “Cooing” or musical diastolic murmurs suggest eversion of an aortic cusp vibrating in the regurgitant stream.


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InternalMed_Harrison. A mid-systolic ejection murmur is frequently audible in isolated AR. It is generally heard best at the base of the heart and is transmitted along the carotid arteries. This murmur may be quite loud without signifying aortic obstruction. A third murmur sometimes heard in patients with severe AR is the Austin Flint murmur, a soft, low-pitched, rumbling mid-to-late diastolic murmur. It is probably produced by the diastolic displacement of the anterior leaflet of the mitral valve by the AR stream and is not associated with hemodynamically significant mitral obstruction. The auscultatory features of AR are intensified by strenuous and sustained handgrip, which augments systemic vascular resistance. In acute severe AR, the elevation of LV end-diastolic pressure may lead to early closure of the mitral valve, a soft S1, a pulse pressure that is not particularly wide, and a soft, short, early diastolic murmur of AR.


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InternalMed_Harrison. LABORATORY EXAMINATION ECG In patients with chronic severe AR, the ECG signs of LV hypertrophy become manifest (Chap. 268). In addition, these patients frequently exhibit ST-segment depression and T-wave inversion in leads I, aVL, V5, and V6 (“LV strain”). Left-axis deviation and/or QRS prolongation denote diffuse myocardial disease, generally associated with patchy fibrosis, and usually signify a poor prognosis.


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InternalMed_Harrison. Echocardiogram LV size is increased in chronic AR and systolic function is normal or even supernormal until myocardial contractility declines, as signaled by a decrease in EF or increase in the end-systolic dimension. A rapid, high-frequency diastolic fluttering of the anterior mitral leaflet produced by the impact of the regurgitant jet is a characteristic finding. The echocardiogram is also useful in determining the cause of AR, by detecting dilation of the aortic annulus and root, aortic dissection (see Fig. 270e-5), or primary leaflet pathology. With severe AR, the central jet width assessed by color flow Doppler imaging exceeds 65% of the LV outflow tract, the regurgitant volume is ≥60 mL/beat, the regurgitant fraction is ≥50%, and there is diastolic flow reversal in the proximal descending thoracic aorta. The continuous-wave Doppler profile of the AR jet shows a rapid deceleration time in patients with acute severe AR, due to the rapid increase in LV diastolic pressure.


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InternalMed_Harrison. descending thoracic aorta. The continuous-wave Doppler profile of the AR jet shows a rapid deceleration time in patients with acute severe AR, due to the rapid increase in LV diastolic pressure. Surveillance transthoracic echocardiography forms the cornerstone of longitudinal follow-up and allows for the early detection of changes in LV size and/or function. For patients in whom transthoracic echocardiography (TTE) is limited by poor acoustical windows or inadequate semiquantitative assessment of LV function or the severity of the regurgitation, cardiac magnetic resonance imaging (MRI) can be performed. This modality also allows for accurate assessment of aortic size and contour. Transesophageal echocardiography (TEE) can also provide detailed anatomic assessment of the valve, root, and portions of the aorta.


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InternalMed_Harrison. Chest X-Ray In chronic severe AR, the apex is displaced downward and to the left in the frontal projection. In the left anterior oblique and lateral projections, the LV is displaced posteriorly and encroaches on the spine. When AR is caused by primary disease of the aortic root, aneurysmal dilation of the aorta may be noted, and the aorta may fill the retrosternal space in the lateral view. Echocardiography, cardiac MRI, and chest CT angiography are more sensitive than the chest x-ray for the detection of root and ascending aortic enlargement. Cardiac Catheterization and Angiography When needed, right and left heart catheterization with contrast aortography can provide confirmation of the magnitude of regurgitation and the status of LV function. Coronary angiography is performed routinely in appropriate patients prior to surgery. ACUTE AORTIC REGURGITATION (FIG. 283-6)


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InternalMed_Harrison. ACUTE AORTIC REGURGITATION (FIG. 283-6) Patients with acute severe AR may respond to intravenous diuretics and vasodilators (such as sodium nitroprusside), but stabilization is usually short-lived and operation is indicated urgently. Intraaortic balloon counterpulsation is contraindicated. Beta blockers are also best avoided so as not to reduce the CO further or slow the heart rate, thus allowing more time for diastolic filling of the LV. Surgery is the treatment of choice and is usually necessary within 24 h of diagnosis.


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InternalMed_Harrison. Early symptoms of dyspnea and effort intolerance respond to treatment with diuretics; vasodilators (ACE inhibitors, dihydropyridine calcium channel blockers, or hydralazine) may be useful as well. Surgery can then be performed in a more controlled setting. The use of vasodilators to extend the compensated phase of chronic severe AR before the onset of symptoms or the development of LV dysfunction is more controversial and less well established. Systolic blood pressure should be controlled (goal <140 mmHg) in patients with chronic AR, and vasodilators are an excellent first choice as antihypertensive agents. It is often difficult to achieve adequate control because of the increased stroke volume that accompanies severe AR. Cardiac arrhythmias and systemic infections are poorly tolerated in patients with severe AR and must be treated promptly and vigorously. Although nitroglycerin and long-acting nitrates are not as helpful in relieving anginal pain as they are in patients with ischemic


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InternalMed_Harrison. patients with severe AR and must be treated promptly and vigorously. Although nitroglycerin and long-acting nitrates are not as helpful in relieving anginal pain as they are in patients with ischemic heart disease, they are worth a trial. Patients with


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InternalMed_Harrison. Vena contracta >0.6 cm (stage B) Holodiastolic aortic flow reversal Vena contracta °0.6 cm vena contracta >0.6 cm ERO ˜0.3 cm2 ERO <0.3 cm2 LV dilation O ˜0.3 cm


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InternalMed_Harrison. FIGURE 283-6 Management of patients with aortic regurgitation. See legend for Fig. 283-2 for explanation of treatment recommendations (Class I, IIa, and IIb) and disease stages (B, C1, C2, D). Preoperative coronary angiography should be performed routinely as determined by age, symptoms, and coronary risk factors. Cardiac catheterization and angiography may also be helpful when there is a discrepancy between clinical and noninvasive findings. Patients who do not meet criteria for intervention should be monitored periodically with clinical and echocardiographic follow-up. AR, aortic regurgitation; AVR, aortic valve replacement (valve repair may be appropriate in selected patients); ERO, effective regurgitant orifice; LV, left ventricular; LVEDD, left ventricular end-diastolic dimension; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; RF, regurgitant fraction; RVol, regurgitant volume. (Adapted from RA Nishimura et al: 2014 AHA/ACC Guideline for


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InternalMed_Harrison. left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; RF, regurgitant fraction; RVol, regurgitant volume. (Adapted from RA Nishimura et al: 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease. J Am Coll Cardiol doi: 10.1016/j.jacc.2014.02.536, 2014, with permission.) syphilitic aortitis should receive a full course of penicillin therapy (Chap. 206). Beta blockers and the angiotensin receptor blocker losartan may be useful to retard the rate of aortic root enlargement in young patients with Marfan’s syndrome and aortic root dilation. Early reports of the efficacy of losartan in patients with Marfan’s syndrome have led to its use in other populations of patients including those with BAV disease and aortopathy. The use of beta blockers in patients with valvular AR was previously felt to be relatively contraindicated due to concerns that the resulting slowing of the heart rate would allow more time for diastolic regurgitation.


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InternalMed_Harrison. in patients with valvular AR was previously felt to be relatively contraindicated due to concerns that the resulting slowing of the heart rate would allow more time for diastolic regurgitation. More recent observational reports, however, suggest that beta blockers may provide functional benefit in patients with chronic AR. Beta blockers can sometimes provide incremental blood pressure lowering in patients with chronic AR and hypertension. Patients with severe AR, particularly those with an associated aortopathy, should avoid isometric exercises.


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InternalMed_Harrison. In deciding on the advisability and proper timing of surgical treatment, two points should be kept in mind: (1) patients with chronic severe AR usually do not become symptomatic until after the development of myocardial dysfunction; and (2) when delayed too long (defined as >1 year from onset of symptoms or LV dysfunction), surgical treatment often does not restore normal LV function. Therefore, in patients with chronic severe AR, careful clinical follow-up and noninvasive testing with echocardiography at approximately 6-to 12-month intervals are necessary if operation is to be undertaken at the optimal time, i.e., after the onset of LV dysfunction but prior to the development of severe symptoms. Exercise testing may be helpful to assess effort tolerance more objectively. Operation can be deferred as long as the patient both remains asymptomatic and retains normal LV function without severe chamber dilation.


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InternalMed_Harrison. AVR is indicated for the treatment of severe AR in symptomatic patients irrespective of LV function. In general, the operation should be carried out in asymptomatic patients with severe AR and progressive LV dysfunction defined by an LVEF <50%, an LV end-systolic dimension >50 mm, or an LV diastolic dimension >65 mm. Smaller dimensions may be appropriate thresholds in individuals of smaller stature. Patients with severe AR without indications for operation should be followed by clinical and echocardiographic examination every 6–12 months. FIGURE 283-7 Valve-sparing aortic root reconstruction (David procedure). (From P Steltzer et al [eds]: Valvular Heart Disease: A Companion to Braunwald’s Heart Disease, 3rd ed, Fig 12-27, p. 200.)


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InternalMed_Harrison. Surgical options for management of aortic valve and root disease have expanded considerably over the past decade. AVR with a suitable mechanical or tissue prosthesis is generally necessary in patients with rheumatic AR and in many patients with other forms of regurgitation. Rarely, when a leaflet has been perforated during infective endocarditis or torn from its attachments to the aortic annulus by thoracic trauma, primary surgical repair may be possible. When AR is due to aneurysmal dilation of the root or proximal ascending aorta rather than to primary valve involvement, it may be possible to reduce or eliminate the regurgitation by narrowing the annulus or by excising a portion of the aortic root without replacing the valve. Elective, valve-sparing aortic root reconstruction generally involves reimplantation of the valve in a contoured graft with reattachment of the coronary artery buttons into the side of the graft and is best undertaken in specialized surgical centers (Fig.


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InternalMed_Harrison. involves reimplantation of the valve in a contoured graft with reattachment of the coronary artery buttons into the side of the graft and is best undertaken in specialized surgical centers (Fig. 283-7). Resuspension of the native aortic valve leaflets is possible in approximately 50% of patients with acute AR in the setting of type A aortic dissection. In other conditions, however, regurgitation can be effectively eliminated only by replacing the aortic valve, the dilated or aneurysmal ascending aorta responsible for the regurgitation, and implanting a composite valve-graft conduit. This formidable procedure entails a higher risk than isolated AVR.


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InternalMed_Harrison. As in patients with other valvular abnormalities, both the operative risk and the late mortality rate are largely dependent on the stage of the disease and myocardial function at the time of operation. The overall operative mortality rate for isolated AVR (performed for either or both AS or AR) is approximately 2% (Table 283-2). However, patients with AR, marked cardiac enlargement, and prolonged LV dysfunction experience an operative mortality rate of approximately 10% and a late mortality rate of approximately 5% per year due to LV failure despite a technically satisfactory operation. Nonetheless, because of the very poor prognosis with medical management, even patients with LV systolic failure should be considered for operation. Patients with acute severe AR require prompt surgical treatment, which may be lifesaving.


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InternalMed_Harrison. Patients with acute severe AR require prompt surgical treatment, which may be lifesaving. Mitral valve Disease Patrick T. O’Gara, Joseph Loscalzo The role of the physical examination in the evaluation of patients with valvular heart disease is also considered in Chaps. 51e and 267; of electrocardiography (ECG) in Chap. 268; of echocardiography and other noninvasive imaging techniques in Chap. 270e; and of cardiac 284 catheterization and angiography in Chap. 272.


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InternalMed_Harrison. Rheumatic fever is the leading cause of mitral stenosis (MS) (Table 284-1). Other less common etiologies of obstruction to left ventricular inflow include congenital mitral valve stenosis, cor triatriatum, mitral annular calcification with extension onto the leaflets, systemic lupus erythematosus, rheumatoid arthritis, left atrial myxoma, and infective endocarditis with large vegetations. Pure or predominant MS occurs in approximately 40% of all patients with rheumatic heart disease and a history of rheumatic fever (Chap. 381). In other patients with rheumatic heart disease, lesser degrees of MS may accompany mitral regurgitation (MR) and aortic valve disease. With reductions in the incidence of acute rheumatic fever, particularly in temperate climates and developed countries, the incidence of MS has declined considerably over the past several decades. However, it remains a major problem in developing nations, especially in tropical and semitropical climates.


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InternalMed_Harrison. In rheumatic MS, chronic inflammation leads to diffuse thickening of the valve leaflets with formation of fibrous tissue and/or calcific deposits. The mitral commissures fuse, the chordae tendineae fuse and shorten, the valvular cusps become rigid, and these changes, in turn, lead to narrowing at the apex of the funnel-shaped (“fish-mouth”) valve. Although the initial insult to the mitral valve is rheumatic, later changes may be exacerbated by a nonspecific process resulting from trauma to the valve due to altered flow patterns. Calcification of the Mitral stenosis Rheumatic fever Congenital Severe mitral annular calcification SLE, RA Mitral regurgitation Acute Endocarditis Papillary muscle rupture (post-MI) Trauma Chordal rupture/leaflet flail (MVP, IE) Chronic Myxomatous (MVP) Rheumatic fever Endocarditis (healed) Mitral annular calcification Congenital (cleft, AV canal) HOCM with SAM Ischemic (LV remodeling) Dilated cardiomyopathy Radiation


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InternalMed_Harrison. Chronic Myxomatous (MVP) Rheumatic fever Endocarditis (healed) Mitral annular calcification Congenital (cleft, AV canal) HOCM with SAM Ischemic (LV remodeling) Dilated cardiomyopathy Radiation Abbreviations: AV, atrioventricular; IE, infective endocarditis; HOCM, hypertrophic obstructive cardiomyopathy; LV, left ventricular; MI, myocardial infarction; MVP, mitral valve prolapse; RA, rheumatoid arthritis; SAM, systolic anterior motion; SLE, systemic lupus erythematosus. stenotic mitral valve immobilizes the leaflets and narrows the orifice 1539 further. Thrombus formation and arterial embolization may arise from the calcific valve itself, but in patients with atrial fibrillation (AF), thrombi arise more frequently from the dilated left atrium (LA), particularly from within the LA appendage.


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InternalMed_Harrison. In normal adults, the area of the mitral valve orifice is 4–6 cm2. In the presence of significant obstruction, i.e., when the orifice area is reduced to < ~2 cm2, blood can flow from the LA to the left ventricle (LV) only if propelled by an abnormally elevated left atrioventricular pressure gradient, the hemodynamic hallmark of MS. When the mitral valve opening is reduced to <1.5 cm2, referred to as “severe” MS, an LA pressure of ~25 mmHg is required to maintain a normal cardiac output (CO). The elevated pulmonary venous and pulmonary arterial (PA) wedge pressures reduce pulmonary compliance, contributing to exertional dyspnea. The first bouts of dyspnea are usually precipitated by clinical events that increase the rate of blood flow across the mitral orifice, resulting in further elevation of the LA pressure (see below).


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InternalMed_Harrison. To assess the severity of obstruction hemodynamically, both the transvalvular pressure gradient and the flow rate must be measured (Chap. 272). The latter depends not only on the CO but on the heart rate, as well. An increase in heart rate shortens diastole proportionately more than systole and diminishes the time available for flow across the mitral valve. Therefore, at any given level of CO, tachycardia, including that associated with rapid AF, augments the transvalvular pressure gradient and elevates further the LA pressure. Similar considerations apply to the pathophysiology of tricuspid stenosis.


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InternalMed_Harrison. The LV diastolic pressure and ejection fraction (EF) are normal in isolated MS. In MS and sinus rhythm, the elevated LA and PA wedge pressures exhibit a prominent atrial contraction pattern (a wave) and a gradual pressure decline after the v wave and mitral valve opening (y descent). In severe MS and whenever pulmonary vascular resistance is significantly increased, the PA pressure (PAP) is elevated at rest and rises further during exercise, often causing secondary elevations of right ventricular (RV) end-diastolic pressure and volume. Cardiac Output In patients with severe MS (mitral valve orifice 1–1.5 cm2), the CO is normal or almost so at rest, but rises subnormally during exertion. In patients with very severe MS (valve area <1 cm2), particularly those in whom pulmonary vascular resistance is markedly elevated, the CO is subnormal at rest and may fail to rise or may even decline during activity.


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InternalMed_Harrison. Pulmonary Hypertension The clinical and hemodynamic features of MS are influenced importantly by the level of the PAP. Pulmonary hypertension results from: (1) passive backward transmission of the elevated LA pressure; (2) pulmonary arteriolar constriction (the so-called “second stenosis”), which presumably is triggered by LA and pulmonary venous hypertension (reactive pulmonary hypertension); interstitial edema in the walls of the small pulmonary vessels; and at end stage, organic obliterative changes in the pulmonary vascular bed. Severe pulmonary hypertension results in RV enlargement, secondary tricuspid regurgitation (TR), and pulmonic regurgitation (PR), as well as right-sided heart failure.


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InternalMed_Harrison. In temperate climates, the latent period between the initial attack of rheumatic carditis (in the increasingly rare circumstances in which a history of one can be elicited) and the development of symptoms due to MS is generally about two decades; most patients begin to experience disability in the fourth decade of life. Studies carried out before the development of mitral valvotomy revealed that once a patient with MS became seriously symptomatic, the disease progressed inexorably to death within 2–5 years.


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InternalMed_Harrison. In patients whose mitral orifices are large enough to accommodate a normal blood flow with only mild elevations of LA pressure, marked elevations of this pressure leading to dyspnea and cough may be precipitated by sudden changes in the heart rate, volume status, or CO, as, for example, with severe exertion, excitement, fever, severe anemia, paroxysmal AF 1540 and other tachycardias, sexual intercourse, pregnancy, and thyrotoxicosis. As MS progresses, lesser degrees of stress precipitate dyspnea, the patient becomes limited in daily activities, and orthopnea and paroxysmal nocturnal dyspnea develop. The development of persistent AF often marks a turning point in the patient’s course and is generally associated with acceleration of the rate at which symptoms progress. Hemoptysis (Chap. 48) results from rupture of pulmonary-bronchial venous connections secondary to pulmonary venous hypertension. It occurs most frequently in patients who have elevated LA pressures without markedly


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InternalMed_Harrison. 48) results from rupture of pulmonary-bronchial venous connections secondary to pulmonary venous hypertension. It occurs most frequently in patients who have elevated LA pressures without markedly elevated pulmonary vascular resistances and is rarely fatal. Recurrent pulmonary emboli (Chap. 300), sometimes with infarction, are an important cause of morbidity and mortality late in the course of MS. Pulmonary infections, i.e., bronchitis, bronchopneumonia, and lobar pneumonia, commonly complicate untreated MS, especially during the winter months.


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InternalMed_Harrison. Pulmonary Changes In addition to the aforementioned changes in the pulmonary vascular bed, fibrous thickening of the walls of the alveoli and pulmonary capillaries occurs commonly in MS. The vital capacity, total lung capacity, maximal breathing capacity, and oxygen uptake per unit of ventilation are reduced (Chap. 306e). Pulmonary compliance falls further as pulmonary capillary pressure rises during exercise. Thrombi and Emboli Thrombi may form in the left atria, particularly within the enlarged atrial appendages of patients with MS. Systemic embolization, the incidence of which is 10–20%, occurs more frequently in patients with AF, in patients >65 years of age, and in those with a reduced CO. However, systemic embolization may be the presenting feature in otherwise asymptomatic patients with only mild MS. (See also Chaps. 51e and 267)


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InternalMed_Harrison. (See also Chaps. 51e and 267) Inspection and Palpation In patients with severe MS, there may be a malar flush with pinched and blue facies. In patients with sinus rhythm and severe pulmonary hypertension or associated tricuspid stenosis (TS), the jugular venous pulse reveals prominent a waves due to vigorous right atrial systole. The systemic arterial pressure is usually normal or slightly low. An RV tap along the left sternal border signifies an enlarged RV. A diastolic thrill may rarely be present at the cardiac apex, with the patient in the left lateral recumbent position.


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InternalMed_Harrison. Auscultation The first heart sound (S1) is usually accentuated in the early stages of the disease and slightly delayed. The pulmonic component of the second heart sound (P2) also is often accentuated with elevated PA pressures, and the two components of the second heart sound (S2) are closely split. The opening snap (OS) of the mitral valve is most readily audible in expiration at, or just medial to, the cardiac apex. This sound generally follows the sound of aortic valve closure (A2) by 0.05–0.12 s. The time interval between A2 and OS varies inversely with the severity of the MS. The OS is followed by a low-pitched, rumbling, diastolic murmur, heard best at the apex with the patient in the left lateral recumbent position (see Fig. 267-5); it is accentuated by mild exercise (e.g., a few rapid sit-ups) carried out just before auscultation. In general, the duration of this murmur correlates with the severity of the stenosis in patients with preserved CO. In patients with sinus rhythm,


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InternalMed_Harrison. rapid sit-ups) carried out just before auscultation. In general, the duration of this murmur correlates with the severity of the stenosis in patients with preserved CO. In patients with sinus rhythm, the murmur often reappears or becomes louder during atrial systole (presystolic accentuation). Soft, grade I or II/VI systolic murmurs are commonly heard at the apex or along the left sternal border in patients with pure MS and do not necessarily signify the presence of MR. Hepatomegaly, ankle edema, ascites, and pleural effusion, particularly in the right pleural cavity, may occur in patients with MS and RV failure.


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InternalMed_Harrison. Associated Lesions With severe pulmonary hypertension, a pansystolic murmur produced by functional TR may be audible along the left sternal border. This murmur is usually louder during inspiration and diminishes during forced expiration (Carvallo’s sign). When the CO is markedly reduced in MS, the typical auscultatory findings, including the diastolic rumbling murmur, may not be detectable (silent MS), but they may reappear as compensation is restored. The Graham Steell murmur of PR, a high-pitched, diastolic, decrescendo blowing murmur along the left sternal border, results from dilation of the pulmonary valve ring and occurs in patients with mitral valve disease and severe pulmonary hypertension. This murmur may be indistinguishable from the more common murmur produced by aortic regurgitation (AR), although it may increase in intensity with inspiration and is accompanied by a loud and often palpable P2.


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InternalMed_Harrison. LABORATORY EXAMINATION ECG In MS and sinus rhythm, the P wave usually suggests LA enlargement (see Fig. 268-8). It may become tall and peaked in lead II and upright in lead V1 when severe pulmonary hypertension or TS complicates MS and right atrial (RA) enlargement occurs. The QRS complex is usually normal. However, with severe pulmonary hypertension, right axis deviation and RV hypertrophy are often present.


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InternalMed_Harrison. Echocardiogram (See also Chap. 270e) Transthoracic echocardiography (TTE) with color flow and spectral Doppler imaging provides critical information, including measurements of mitral inflow velocity during early (E wave) and late (A wave in patients in sinus rhythm) diastolic filling, estimates of the transvalvular peak and mean gradients and of the mitral orifice area, the presence and severity of any associated MR, the extent of leaflet calcification and restriction, the degree of distortion of the subvalvular apparatus, and the anatomic suitability for percutaneous mitral balloon valvotomy (percutaneous mitral balloon valvuloplasty [PMBV]; see below). In addition, TTE provides an assessment of LV and RV function, chamber sizes, an estimation of the PAP based on the tricuspid regurgitant jet velocity, and an indication of the presence and severity of any associated valvular lesions, such as aortic stenosis and/or regurgitation. Transesophageal echocardiography (TEE) provides


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InternalMed_Harrison. jet velocity, and an indication of the presence and severity of any associated valvular lesions, such as aortic stenosis and/or regurgitation. Transesophageal echocardiography (TEE) provides superior images and should be used when TTE is inadequate for guiding management decisions. TEE is especially indicated to exclude the presence of LA thrombus prior to PMBV. The performance of TTE with exercise to evaluate the mean mitral diastolic gradient and PA pressures can be very helpful in the evaluation of patients with MS when there is a discrepancy between the clinical findings and the resting hemodynamics.


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InternalMed_Harrison. Chest X-Ray The earliest changes are straightening of the upper left border of the cardiac silhouette, prominence of the main PAs, dilation of the upper lobe pulmonary veins, and posterior displacement of the esophagus by an enlarged LA. Kerley B lines are fine, dense, opaque, horizontal lines that are most prominent in the lower and mid-lung fields and that result from distention of interlobular septae and lymphatics with edema when the resting mean LA pressure exceeds approximately 20 mmHg.


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InternalMed_Harrison. Like MS, significant MR may also be associated with a prominent diastolic murmur at the apex due to increased antegrade transmitral flow, but in patients with isolated MR, this diastolic murmur commences slightly later than in patients with MS, and there is often clear-cut evidence of LV enlargement. An OS and increased P2 are absent, and S1 is soft or absent. An apical pansystolic murmur of at least grade III/VI intensity as well as an S3 suggest significant MR. Similarly, the apical mid-diastolic murmur associated with severe AR (Austin Flint murmur) may be mistaken for MS but can be differentiated from it because it is not intensified in presystole and becomes softer with administration of amyl nitrite or other arterial vasodilators. TS, which occurs rarely in the absence of MS, may mask many of the clinical features of MS or be clinically silent; when present, the diastolic murmur of TS increases with inspiration and the y descent in the jugular venous pulse is delayed.


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InternalMed_Harrison. Atrial septal defect (Chap. 282) may be mistaken for MS; in both conditions, there is often clinical, ECG, and chest x-ray evidence of RV enlargement and accentuation of pulmonary vascularity. However, the absence of LA enlargement and of Kerley B lines and the demonstration of fixed splitting of S2 with a grade II or III mid-systolic murmur at the mid to upper left sternal border all favor atrial septal defect over MS. Atrial septal defects with large left-to-right shunts may result in functional TS because of the enhanced diastolic flow.


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InternalMed_Harrison. Left atrial myxoma (Chap. 289e) may obstruct LA emptying, causing dyspnea, a diastolic murmur, and hemodynamic changes resembling those of MS. However, patients with an LA myxoma often have features suggestive of a systemic disease, such as weight loss, fever, anemia, systemic emboli, and elevated serum IgG and interleukin 6 (IL-6) concentrations. The auscultatory findings may change markedly with body position. The diagnosis can be established by the demonstration of a characteristic echo-producing mass in the LA with TTE.


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InternalMed_Harrison. Left and right heart catheterization can be useful when there is a discrepancy between the clinical and noninvasive findings, including those from TEE and exercise echocardiographic testing as appropriate. Catheterization is helpful in assessing associated lesions, such as aortic stenosis (AS) and AR. Catheterization and coronary angiography are not usually necessary to aid in decision-making about surgery in patients younger than 65 years of age with typical findings of severe mitral obstruction on physical examination and TTE. In men older than 40 years of age, women older than 45 years of age, and younger patients with coronary risk factors, especially those with positive noninvasive stress tests for myocardial ischemia, coronary angiography is advisable preoperatively to identify patients with critical coronary obstructions that should be bypassed at the time of operation. Computed tomographic coronary angiography (CTCA) (Chap. 270e) is now often used to screen preoperatively for


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InternalMed_Harrison. with critical coronary obstructions that should be bypassed at the time of operation. Computed tomographic coronary angiography (CTCA) (Chap. 270e) is now often used to screen preoperatively for the presence of coronary artery disease (CAD) in patients with valvular heart 1541 disease and low pretest likelihood of CAD. Catheterization and left ventriculography may be useful in patients who have undergone PMBV or previous mitral valve surgery for MS, and who have redeveloped limiting symptoms, especially if questions regarding the severity of the valve lesion(s) remain after noninvasive study.


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InternalMed_Harrison. (Fig. 284-1) Penicillin prophylaxis of group A β-hemolytic streptococcal infections (Chap. 381) for secondary prevention of rheumatic fever is important for at-risk patients with rheumatic MS. Recommendations for infective endocarditis prophylaxis are similar to those for other valve lesions and are restricted to patients at high risk for complications from infection, including patients with a history of endocarditis. In symptomatic patients, some improvement usually occurs with restriction of sodium intake and small doses of oral diuretics. Beta blockers, nondihydropyridine calcium channel blockers (e.g., verapamil or diltiazem), and digitalis glycosides are useful in slowing the ventricular rate of patients with AF. Warfarin therapy targeted to an international normalized ratio (INR) of 2–3 should be administered indefinitely to patients with MS who have AF or a history of thromboembolism. The routine use of warfarin in patients in sinus rhythm with LA enlargement (maximal dimension


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InternalMed_Harrison. Rheumatic MS Very severe MS MVA ˜1 cm2 T½ °220 ms Severe MS MVA ˜1.5 cm2 T½ °150 ms Progressive MS MVA >1.5 cm2 T½ <150 ms Asymptomatic (stage C) Asymptomatic (stage C) Symptomatic (stage D) Symptomatic with no other cause Class I Class IIa Class IIb


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InternalMed_Harrison. FIGURE 284-1 Management of rheumatic mitral stenosis. See legend for Fig. 283-2 for explanation of treatment recommendations (class I, IIa, IIb) and disease stages (C, D). Preoperative coronary angiography should be performed routinely as determined by age, symptoms, and coronary risk factors. Cardiac catheterization and angiography may also be helpful when there is a discrepancy between clinical and noninvasive findings. AF, atrial fibrillation; LA, left atrial; MR, mitral regurgitation; MS, mitral stenosis; MVA, mitral valve area; MVR, mitral valve surgery (repair or replacement); NYHA, New York Heart Association; PCWP, pulmonary capillary wedge pressure; PMBC, percutaneous mitral balloon commissurotomy; and T ½, pressure half-time. (Adapted from RA Nishimura et al: 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease. J Am Coll Cardiol doi: 10.1016/j.jacc.2014.02.536, 2014, with permission.) 1542 >5.5 cm) with or without spontaneous echo contrast is


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InternalMed_Harrison. for the Management of Patients with Valvular Heart Disease. J Am Coll Cardiol doi: 10.1016/j.jacc.2014.02.536, 2014, with permission.) 1542 >5.5 cm) with or without spontaneous echo contrast is more controversial. The novel oral anticoagulants are not approved for use in patients with significant valvular heart disease. If AF is of relatively recent onset in a patient whose MS is not severe enough to warrant PMBV or surgical commissurotomy, reversion to sinus rhythm pharmacologically or by means of electrical countershock is indicated. Usually, cardioversion should be undertaken after the patient has had at least 3 consecutive weeks of anticoagulant treatment to a therapeutic INR. If cardioversion is indicated more urgently, then intravenous heparin should be provided and TEE performed to exclude the presence of LA thrombus before the procedure. Conversion to sinus rhythm is rarely successful or sustained in patients with severe MS, particularly those in whom the LA is especially


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InternalMed_Harrison. to exclude the presence of LA thrombus before the procedure. Conversion to sinus rhythm is rarely successful or sustained in patients with severe MS, particularly those in whom the LA is especially enlarged or in whom AF has been present for more than 1 year.


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InternalMed_Harrison. Unless there is a contraindication, mitral valvotomy is indicated in symptomatic (New York Heart Association [NYHA] Functional Class II–IV) patients with isolated severe MS, whose effective orifice (valve area) is < ~1 cm2/m2 body surface area, or <1.5 cm2 in normal-sized adults. Mitral valvotomy can be carried out by two techniques: PMBV and surgical valvotomy. In PMBV (Figs. 284-2 and 284-3), a catheter is directed into the LA after transseptal puncture, and a single balloon is directed across the valve and inflated in the valvular orifice. Ideal patients have relatively pliable leaflets with little or no commissural calcium. In addition, the subvalvular structures should not be significantly scarred or thickened, and there should be no LA thrombus. The shortand long-term results of this procedure in appropriate patients are similar to those of surgical valvotomy, but with less morbidity and a lower periprocedural mortality rate. Event-free


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InternalMed_Harrison. FIGURE 284-2 Inoue balloon technique for percutaneous mitral balloon valvotomy. A. After transseptal puncture, the deflated balloon catheter is advanced across the interatrial septum, then across the mitral valve and into the left ventricle. B–D. The balloon is inflated stepwise within the mitral orifice. Mean mitral gradient 3 mmHg Cardiac output 3.8 L/min Mitral valve area 1.8 cm2 LV LA Mean mitral gradient 15 mmHg Cardiac output 3 L/min Mitral valve area 0.6 cm2 40 20 0 LV LA FIGURE 284-3 Simultaneous left atrial (LA) and left ventricular (LV) pressure before and after percutaneous mitral balloon valvuloplasty (PMBV) in a patient with severe mitral stenosis. ECG, electrocardiogram.


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InternalMed_Harrison. (Courtesy of Raymond G. McKay, MD; with permission.) survival in younger (<45 years) patients with pliable valves is excellent, with rates as high as 80–90% over 3–7 years. Therefore, PMBV has become the procedure of choice for such patients when it can be performed by a skilled operator in a high-volume center. TTE is helpful in identifying patients for the percutaneous procedure, and TEE is performed routinely to exclude LA thrombus and to assess the degree of MR at the time of the scheduled procedure. An “echo score” has been developed to help guide decision-making. The score accounts for the degree of leaflet thickening, calcification, and mobility, and for the extent of subvalvular thickening. A lower score predicts a higher likelihood of successful PMBV.


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InternalMed_Harrison. In patients in whom PMBV is not possible or unsuccessful, or in many patients with restenosis after previous surgery, an “open” valvotomy using cardiopulmonary bypass is necessary. In addition to opening the valve commissures, it is important to loosen any subvalvular fusion of papillary muscles and chordae tendineae; to remove large deposits of calcium, thereby improving valvular function; and to remove atrial thrombi. The perioperative mortality rate is ~2%.


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InternalMed_Harrison. Successful valvotomy is defined by a 50% reduction in the mean mitral valve gradient and a doubling of the mitral valve area. Successful valvotomy, whether balloon or surgical, usually results in striking symptomatic and hemodynamic improvement and prolongs survival. However, there is no evidence that the procedure improves the prognosis of patients with slight or no functional impairment. Therefore, unless recurrent systemic embolization or severe pulmonary hypertension has occurred (PA systolic pressures >50 mmHg at rest or >60 mmHg with exercise), valvotomy is not recommended for patients who are entirely asymptomatic and/or who have mild or moderate stenosis (mitral valve area >1.5 cm2). When there is little symptomatic improvement after valvotomy, it is likely that the procedure was ineffective, that it induced MR, or that associated valvular or myocardial disease was present. About half of all patients undergoing surgical mitral valvotomy require reoperation by 10 years. In the


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InternalMed_Harrison. ineffective, that it induced MR, or that associated valvular or myocardial disease was present. About half of all patients undergoing surgical mitral valvotomy require reoperation by 10 years. In the pregnant patient with MS, valvotomy should be carried out if pulmonary congestion occurs despite intensive medical treatment. PMBV is the preferred strategy in this setting and is performed with TEE and no or minimal x-ray exposure.


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InternalMed_Harrison. Mitral valve replacement (MVR) is necessary in patients with MS and significant associated MR, those in whom the valve has been severely distorted by previous transcatheter or operative aData are for the first two quarters of calendar year 2013, during which 1004 sites reported a total of 135,666 procedures. Data are available from the Society of Thoracic Surgeons at http://www.sts.org/sites/default/files/documents/2013_3rdHarvestExecutiveSummary.pdf. Abbreviations: CAB, coronary artery bypass; MVR, mitral valve replacement; MVRp, mitral valve repair.


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InternalMed_Harrison. manipulation, or those in whom the surgeon does not find it possible to improve valve function significantly with valvotomy. MVR is now routinely performed with preservation of the chordal attachments to optimize LV functional recovery. Perioperative mortality rates with MVR vary with age, LV function, the presence of CAD, and associated comorbidities. They average 5% overall but are lower in young patients and may be twice as high in patients >65 years of age with significant comorbidities (Table 284-2). Because there are also long-term complications of valve replacement, patients in whom preoperative evaluation suggests the possibility that MVR may be required should be operated on only if they have severe MS—i.e., an orifice area ≤1.5 cm2—and are in NYHA Class III, i.e., symptomatic with ordinary activity despite optimal medical therapy. The overall 10-year survival of surgical survivors is ~70%. Long-term prognosis is worse in patients >65 years of age and those with marked


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InternalMed_Harrison. with ordinary activity despite optimal medical therapy. The overall 10-year survival of surgical survivors is ~70%. Long-term prognosis is worse in patients >65 years of age and those with marked disability and marked depression of the CO preoperatively. Pulmonary hypertension and RV dysfunction are additional risk factors for poor outcome.


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InternalMed_Harrison. MR may result from an abnormality or disease process that affects any one or more of the five functional components of the mitral valve apparatus (leaflets, annulus, chordae tendineae, papillary muscles, and subjacent myocardium) (Table 284-1). Acute MR can occur in the setting of acute myocardial infarction (MI) with papillary muscle rupture (Chap. 295), following blunt chest wall trauma, or during the course of infective endocarditis. With acute MI, the posteromedial papillary muscle is involved much more frequently than the anterolateral papillary muscle because of its singular blood supply. Transient, acute MR can occur during periods of active ischemia and bouts of angina pectoris. Rupture of chordae tendineae can result in “acute-on-chronic MR” in patients with myxomatous degeneration of the valve apparatus.


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InternalMed_Harrison. Chronic MR can result from rheumatic disease, mitral valve prolapse (MVP), extensive mitral annular calcification, congenital valve defects, hypertrophic obstructive cardiomyopathy (HOCM), and dilated cardiomyopathy (Chap. 287). Distinction also should be drawn between primary (degenerative, organic) MR, in which the leaflets and/or chordae tendineae are primarily responsible for abnormal valve function, and functional (secondary) MR, in which the leaflets and chordae tendineae are structurally normal but the regurgitation is caused by annular enlargement, papillary muscle displacement, leaflet tethering, or their combination. The rheumatic process produces rigidity, deformity, and retraction of the valve cusps and commissural fusion, as well as shortening, contraction, and fusion of the chordae tendineae. The MR associated with both MVP and HOCM is usually dynamic in nature. MR in HOCM occurs as a consequence of anterior papillary muscle displacement and systolic anterior motion of


InternalMed_Harrison

InternalMed_Harrison. chordae tendineae. The MR associated with both MVP and HOCM is usually dynamic in nature. MR in HOCM occurs as a consequence of anterior papillary muscle displacement and systolic anterior motion of the anterior mitral valve leaflet into the narrowed LV outflow tract. Annular calcification is especially prevalent among patients with advanced renal disease and is commonly observed in women >65 years of age with hypertension and diabetes. MR may occur as a congenital anomaly (Chap. 282), most commonly as a defect of the endocardial 1543 cushions (atrioventricular cushion defects). A cleft anterior mitral valve leaflet accompanies primum atrial septal defect. Chronic MR is frequently secondary to ischemia and may occur as a consequence of ventricular remodeling, papillary muscle displacement, and leaflet tethering, or with fibrosis of a papillary muscle, in patients with healed MI(s) and ischemic cardiomyopathy. Similar mechanisms of annular dilation and ventricular remodeling contribute


InternalMed_Harrison

InternalMed_Harrison. and leaflet tethering, or with fibrosis of a papillary muscle, in patients with healed MI(s) and ischemic cardiomyopathy. Similar mechanisms of annular dilation and ventricular remodeling contribute to the MR that occurs among patients with nonischemic forms of dilated cardiomyopathy once the LV end-diastolic dimension reaches 6 cm.


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InternalMed_Harrison. Irrespective of cause, chronic severe MR is often progressive, because enlargement of the LA places tension on the posterior mitral leaflet, pulling it away from the mitral orifice and thereby aggravating the valvular dysfunction. Similarly, LV dilation increases the regurgitation, which, in turn, enlarges the LA and LV further, resulting in a vicious circle; hence the aphorism, “mitral regurgitation begets mitral regurgitation.”


InternalMed_Harrison

InternalMed_Harrison. The resistance to LV emptying (LV afterload) is reduced in patients with MR. As a consequence, the LV is decompressed into the LA during ejection, and with the reduction in LV size during systole, there is a rapid decline in LV tension. The initial compensation to MR is more complete LV emptying. However, LV volume increases progressively with time as the severity of the regurgitation increases and as LV contractile function deteriorates. This increase in LV volume is often accompanied by a reduced forward CO. LV compliance is often increased, and thus, LV diastolic pressure does not increase until late in the course. The regurgitant volume varies directly with the LV systolic pressure and the size of the regurgitant orifice; the latter, in turn, is influenced by the extent of LV and mitral annular dilation. Because EF rises in severe MR in the presence of normal LV function, even a modest reduction in this parameter (<60%) reflects significant dysfunction.


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InternalMed_Harrison. During early diastole, as the distended LA empties, there is a particularly rapid y descent in the absence of accompanying MS. A brief, early diastolic LA-LV pressure gradient (often generating a rapid filling sound [S3] and mid-diastolic murmur masquerading as MS) may occur in patients with pure, severe MR as a result of the very rapid flow of blood across a normal-sized mitral orifice.


InternalMed_Harrison

InternalMed_Harrison. Semiquantitative estimates of LV ejection fraction (LVEF), CO, PA systolic pressure, regurgitant volume, regurgitant fraction (RF), and the effective regurgitant orifice area can be obtained during a careful Doppler echocardiographic examination. These measurements can also be obtained accurately with cardiac magnetic resonance (CMR) imaging, although this technology is not widely available. Left and right heart catheterization with contrast ventriculography is used less frequently. Severe, nonischemic MR is defined by a regurgitant volume ≥60 mL/beat, RF ≥50%, and effective regurgitant orifice area ≥0.40 cm2. Severe ischemic MR, however, is usually associated with an effective regurgitant orifice area of >0.2 cm2. In the latter instance, lesser degrees of MR carry relatively greater prognostic weight.


InternalMed_Harrison

InternalMed_Harrison. LA Compliance In acute severe MR, the regurgitant volume is delivered into a normal-sized LA having normal or reduced compliance. As a result, LA pressures rise markedly for any increase in LA volume. The v wave in the LA pressure pulse is usually prominent, LA and pulmonary venous pressures are markedly elevated, and pulmonary edema is common. Because of the rapid rise in LA pressures during ventricular systole, the murmur of acute MR is early in timing and decrescendo in configuration ending well before S2, as a reflection of the progressive diminution in the LV-LA pressure gradient. LV systolic function in acute MR may be normal, hyperdynamic, or reduced, depending on the clinical context.


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InternalMed_Harrison. Patients with chronic severe MR, on the other hand, develop marked LA enlargement and increased LA compliance with little if any increase in LA and pulmonary venous pressures for any increase in LA volume. The LA v wave is relatively less prominent. The murmur of chronic MR is classically holosystolic in timing and plateau in configuration, as a reflection of the near-constant LV-LA pressure gradient. These patients usually complain of severe fatigue and exhaustion secondary 1544 to a low forward CO, whereas symptoms resulting from pulmonary congestion are less prominent initially; AF is almost invariably present once the LA dilates significantly.


InternalMed_Harrison

InternalMed_Harrison. Patients with chronic mild-to-moderate, isolated MR are usually asymptomatic. This form of LV volume overload is well tolerated. Fatigue, exertional dyspnea, and orthopnea are the most prominent complaints in patients with chronic severe MR. Palpitations are common and may signify the onset of AF. Right-sided heart failure, with painful hepatic congestion, ankle edema, distended neck veins, ascites, and secondary TR, occurs in patients with MR who have associated pulmonary vascular disease and pulmonary hypertension. Acute pulmonary edema is common in patients with acute severe MR. In patients with chronic severe MR, the arterial pressure is usually normal, although the carotid arterial pulse may show a sharp, low-volume upstroke owing to the reduced forward CO. A systolic thrill is often palpable at the cardiac apex, the LV is hyperdynamic with a brisk systolic impulse and a palpable rapid-filling wave (S3), and the apex beat is often displaced laterally.


InternalMed_Harrison

InternalMed_Harrison. In patients with acute severe MR, the arterial pressure may be reduced with a narrow pulse pressure, the jugular venous pressure and wave forms may be normal or increased and exaggerated, the apical impulse is not displaced, and signs of pulmonary congestion are prominent.


InternalMed_Harrison

InternalMed_Harrison. Auscultation S1 is generally absent, soft, or buried in the holosystolic murmur of chronic, severe MR. In patients with severe MR, the aortic valve may close prematurely, resulting in wide but physiologic splitting of S2. A low-pitched S3 occurring 0.12–0.17 s after the aortic valve closure sound, i.e., at the completion of the rapid-filling phase of the LV, is believed to be caused by the sudden tensing of the papillary muscles, chordae tendineae, and valve leaflets. It may be followed by a short, rumbling, mid-diastolic murmur, even in the absence of structural MS. A fourth heart sound is often audible in patients with acute severe MR who are in sinus rhythm. A presystolic murmur is not ordinarily heard with isolated MR.


InternalMed_Harrison

InternalMed_Harrison. A systolic murmur of at least grade III/VI intensity is the most characteristic auscultatory finding in chronic severe MR. It is usually holosystolic (see Fig. 267-5A), but as previously noted, it is decrescendo and ceases in mid to late systole in patients with acute severe MR. The systolic murmur of chronic MR is usually most prominent at the apex and radiates to the axilla. However, in patients with ruptured chordae tendineae or primary involvement of the posterior mitral leaflet with prolapse or flail, the regurgitant jet is eccentric, directed anteriorly, and strikes the LA wall adjacent to the aortic root. In this situation, the systolic murmur is transmitted to the base of the heart and, therefore, may be confused with the murmur of AS. In patients with ruptured chordae tendineae, the systolic murmur may have a cooing or “seagull” quality, whereas a flail leaflet may produce a murmur with a musical quality. The systolic murmur of chronic MR not due to MVP is intensified by


InternalMed_Harrison

InternalMed_Harrison. the systolic murmur may have a cooing or “seagull” quality, whereas a flail leaflet may produce a murmur with a musical quality. The systolic murmur of chronic MR not due to MVP is intensified by isometric exercise (handgrip) but is reduced during the strain phase of the Valsalva maneuver because of the associated decrease in LV preload.


InternalMed_Harrison

InternalMed_Harrison. LABORATORY EXAMINATION ECG In patients with sinus rhythm, there is evidence of LA enlargement, but RA enlargement also may be present when pulmonary hypertension is significant and affects RV function. Chronic severe MR is frequently associated with AF. In many patients, there is no clear-cut ECG evidence of enlargement of either ventricle. In others, the signs of eccentric LV hypertrophy are present.


InternalMed_Harrison

InternalMed_Harrison. Echocardiogram TTE is indicated to assess the mechanism of the MR and its hemodynamic severity. LV function can be assessed from LV end-diastolic and end-systolic volumes and EF. Observations can be made regarding leaflet structure and function, chordal integrity, LA and LV size, annular calcification, and regional and global LV systolic function. Doppler imaging should demonstrate the width or area of the color flow MR jet within the LA, the duration and intensity of the continuous wave Doppler signal, the pulmonary venous flow contour, the early peak mitral inflow velocity, and quantitative measures of regurgitant volume, RF, and effective regurgitant orifice area. In addition, the PAPs can be estimated from the TR jet velocity. TTE is also indicated to follow the course of patients with chronic MR and to provide rapid assessment for any clinical change. The echocardiogram in patients with MVP is described in the next section. TEE provides greater anatomic detail than TTE (see Fig.


InternalMed_Harrison

InternalMed_Harrison. chronic MR and to provide rapid assessment for any clinical change. The echocardiogram in patients with MVP is described in the next section. TEE provides greater anatomic detail than TTE (see Fig. 270e-5). Exercise testing with TTE can be useful to assess exercise capacity as well as any dynamic change in MR severity, PA systolic pressures, and biventricular function, for patients in whom there is a discrepancy between clinical findings and the results of functional testing performed at rest.


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InternalMed_Harrison. Chest X-Ray The LA and LV are the dominant chambers in chronic MR. Late in the course of the disease, the LA may be massively enlarged and forms the right border of the cardiac silhouette. Pulmonary venous congestion, interstitial edema, and Kerley B lines are sometimes noted. Marked calcification of the mitral leaflets occurs commonly in patients with long-standing, combined rheumatic MR and MS. Calcification of the mitral annulus may be visualized, particularly on the lateral view of the chest. Patients with acute severe MR may have asymmetric pulmonary edema if the regurgitant jet is directed predominantly to the orifice of an upper lobe pulmonary vein. MEDICAL TREATMENT (FIG. 284-4)


InternalMed_Harrison

InternalMed_Harrison. The management of chronic severe MR depends to some degree on its cause. Warfarin should be provided once AF intervenes with a target INR of 2–3. Novel oral anticoagulants are not approved for this indication. Cardioversion should be considered depending on the clinical context and LA size. In contrast to the acute setting, there are no large, long-term prospective studies to substantiate the use of vasodilators for the treatment of chronic, isolated severe MR with preserved LV systolic function in the absence of systemic hypertension. The severity of MR in the setting of an ischemic or nonischemic dilated cardiomyopathy may diminish with aggressive guideline-directed treatment of heart failure including the use of diuretics, beta blockers, angiotensin-converting enzyme (ACE) inhibitors, digitalis, and biventricular pacing (cardiac resynchronization therapy [CRT]) when otherwise indicated. Asymptomatic patients with severe MR in sinus rhythm with normal LV size and systolic function


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InternalMed_Harrison. digitalis, and biventricular pacing (cardiac resynchronization therapy [CRT]) when otherwise indicated. Asymptomatic patients with severe MR in sinus rhythm with normal LV size and systolic function should avoid isometric forms of exercise.


InternalMed_Harrison

InternalMed_Harrison. Patients with acute severe MR require urgent stabilization and preparation for surgery. Diuretics, intravenous vasodilators (particularly sodium nitroprusside), and even intraaortic balloon counterpulsation may be needed for patients with post-MI papillary muscle rupture or other forms of acute severe MR.


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InternalMed_Harrison. In the selection of patients with chronic, nonischemic, primary or organic, severe MR for surgical treatment, the often slowly progressive nature of the condition must be balanced against the immediate and long-term risks associated with operation. These risks are significantly lower for primary valve repair than for valve replacement (Table 287-2). Repair usually consists of valve reconstruction using a variety of valvuloplasty techniques and insertion of an annuloplasty ring. Repair spares the patient the long-term adverse consequences of valve replacement, including thromboembolic and hemorrhagic complications in the case of mechanical prostheses and late valve failure necessitating repeat valve replacement in the case of bioprostheses. In addition, by preserving the integrity of the papillary muscles, subvalvular apparatus, and chordae tendineae, mitral repair and valvuloplasty maintain LV function to a relatively greater degree.


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InternalMed_Harrison. Vena contracta ˜0.7 cm RVol ˜60% cc RF ˜50% ERO ˜0.4 cm2 LV dilation (stage B) Vena contracta ˜0.7 cm RVol <60 cc RF <50% ERO <0.4 cm2


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InternalMed_Harrison. FIGURE 284-4 Management of mitral regurgitation. See legend for Fig. 283-2 for explanation of treatment recommendations (class I, IIa, IIb) and disease stages (B, C1, C2, D). Preoperative coronary angiography should be performed routinely as determined by age, symptoms, and coronary risk factors. Cardiac catheterization and angiography may also be helpful when there is a discrepancy between clinical and noninvasive findings. AF, atrial fibrillation; CAD, coronary artery disease; CRT, cardiac resynchronization therapy; ERO, effective regurgitant orifice; HF, heart failure; LV, left ventricular; LVEF, left ventricular ejection fraction; LVESD, left ventricular end-systolic dimension; MR, mitral regurgitation, MV, mitral valve; MVR, mitral valve replacement; NYHA, New York Heart Association; PASP, pulmonary artery systolic pressure; RF, regurgitant fraction; RVol, regurgitant volume; and Rx, therapy. ∗Mitral valve repair preferred over MVR when possible. (Adapted from RA Nishimura et al:


InternalMed_Harrison

InternalMed_Harrison. PASP, pulmonary artery systolic pressure; RF, regurgitant fraction; RVol, regurgitant volume; and Rx, therapy. ∗Mitral valve repair preferred over MVR when possible. (Adapted from RA Nishimura et al: 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Disease. J Am Coll Cardiol doi: 10.1016/j.jacc.2014.02.536, 2014, with permission.)


InternalMed_Harrison

InternalMed_Harrison. Surgery for chronic nonischemic severe MR is indicated once symptoms occur, especially if valve repair is feasible (Fig. 284-4). Other indications for early consideration of mitral valve repair include recent-onset AF and pulmonary hypertension defined as a systolic PA pressure ≥50 mmHg at rest or ≥60 mmHg with exercise. Surgical treatment of chronic nonischemic severe MR is indicated for asymptomatic patients when LV dysfunction is progressive with the LVEF falling below 60% and/or end-systolic dimension increasing beyond 40 mm. These aggressive recommendations for surgery are predicated on the outstanding results achieved with mitral valve repair particularly when applied to patients with myxomatous disease such as that associated with prolapse or flail leaflet. Indeed primary valvuloplasty repair of patients younger than 75 years with normal LV systolic function and no CAD can now be performed by experienced surgeons with <1% perioperative mortality risk. The risk of stroke,


InternalMed_Harrison

InternalMed_Harrison. repair of patients younger than 75 years with normal LV systolic function and no CAD can now be performed by experienced surgeons with <1% perioperative mortality risk. The risk of stroke, however, is also approximately 1%. Repair is feasible in up to 95% of patients with myxomatous disease operated on by a high-volume surgeon in a referral center of excellence. Long-term durability is excellent; the incidence of reoperative surgery for failed primary repair is ~1% per year for the first 10 years after surgery. For patients with AF, left or biatrial maze surgery, or radiofrequency, isolation of the pulmonary veins is often performed to reduce the risk of recurrent postoperative AF.


InternalMed_Harrison

InternalMed_Harrison. The surgical management of patients with functional, ischemic MR is more complicated and most often involves simultaneous coronary artery revascularization. Current surgical practice includes annuloplasty repair with an undersized, rigid ring or chord-sparing valve replacement for patients with moderate or greater degrees of MR. Valve repair for ischemic MR is associated with lower perioperative mortality rates but higher rates of recurrent MR over time. In patients with ischemic MR and significantly impaired LV systolic function (EF <30%), the risk of surgery is higher, recovery of LV performance is incomplete, and long-term survival is reduced. Referral for surgery must be individualized and made only after aggressive attempts with guideline-directed medical therapy and CRT, when indicated. The routine performance of valve repair in patients with significant MR in the setting of severe, functional, nonischemic dilated cardiomyopathy has not been shown to improve long-term survival


InternalMed_Harrison

InternalMed_Harrison. The routine performance of valve repair in patients with significant MR in the setting of severe, functional, nonischemic dilated cardiomyopathy has not been shown to improve long-term survival compared with optimal medical therapy. Patients with acute severe MR can often be stabilized temporarily with appropriate medical therapy, but surgical correction will be necessary emergently in the case of papillary muscle rupture and within days to weeks in most other settings.


InternalMed_Harrison

InternalMed_Harrison. When surgical treatment is contemplated, left and right heart catheterization and left ventriculography may be helpful in confirming the presence of severe MR in patients in whom there is a discrepancy between the clinical and TTE findings that cannot be resolved with TEE or CMR. Coronary angiography identifies patients who require concomitant coronary revascularization. FIGURE 284-5 Clip used to grasp the free edges of the anterior and posterior leaflets in their midsections during transcatheter repair of selected patients with mitral regurgitation. (Courtesy of Abbott Vascular. © 2014 Abbott Laboratories. All rights reserved.)


InternalMed_Harrison

InternalMed_Harrison. A transcatheter approach to the treatment of either organic or functional MR may be feasible in selected patients with appropriate anatomy. The proper role of currently available techniques remains under active investigation. One approach involves the deployment of a clip delivered via transseptal puncture that grasps the leading edges of the mitral leaflets in their mid-portion (anterior scallop to posterior scallop or A2-P2; Fig. 284-5). The length and width of the gap between these leading edges dictate patient eligibility. The device is commercially available for the treatment of prohibitive surgical risk patients with severe, degenerative (organic) MR and is undergoing study in the United States for treatment of patients with symptomatic heart failure, reduced LVEF, and severe, functional MR despite guideline-directed medical therapy. A second approach involves the deployment of a device within the coronary sinus that can be adjusted to reduce its circumference, thus secondarily


InternalMed_Harrison

InternalMed_Harrison. MR despite guideline-directed medical therapy. A second approach involves the deployment of a device within the coronary sinus that can be adjusted to reduce its circumference, thus secondarily decreasing the circumference of the mitral annulus and the effective orifice area of the valve much like a surgically implanted ring. Variations in the anatomic relationship of the coronary sinus to the mitral annulus and circumflex coronary artery have limited the applicability of this technique. Attempts to reduce the septal-lateral dimension of a dilated annulus using adjustable cords placed across the LV in a subvalvular location have also been investigated.


InternalMed_Harrison

InternalMed_Harrison. MVP, also variously termed the systolic click-murmur syndrome, Barlow’s syndrome, floppy-valve syndrome, and billowing mitral leaflet syndrome, is a relatively common but highly variable clinical syndrome resulting from diverse pathologic mechanisms of the mitral valve apparatus. Among these are excessive or redundant mitral leaflet tissue, which is commonly associated with myxomatous degeneration and greatly increased concentrations of certain glycosaminoglycans. In most patients with MVP, the cause is unknown, but in some, it appears to be genetically determined. A reduction in the production of type III collagen has been incriminated, and electron microscopy has revealed fragmentation of collagen fibrils.


InternalMed_Harrison

InternalMed_Harrison. MVP is a frequent finding in patients with heritable disorders of connective tissue, including Marfan’s syndrome (Chap. 427), osteogenesis imperfecta, and Ehlers-Danlos syndrome. MVP may be associated with thoracic skeletal deformities similar to but not as severe as those in Marfan’s syndrome, such as a high-arched palate and alterations of the chest and thoracic spine, including the so-called straight back syndrome. In most patients with MVP, myxomatous degeneration is confined to the mitral valve, although the tricuspid and aortic valves may also be affected. The posterior mitral leaflet is usually more affected than the anterior, and the mitral valve annulus is often dilated. In many patients, elongated, redundant, or ruptured chordae tendineae cause or contribute to the regurgitation.


InternalMed_Harrison

InternalMed_Harrison. MVP also may occur rarely as a sequel to acute rheumatic fever, in ischemic heart disease, and in various cardiomyopathies, as well as in 20% of patients with ostium secundum atrial septal defect. MVP may lead to excessive stress on the papillary muscles, which, in turn, leads to dysfunction and ischemia of the papillary muscles and the subjacent ventricular myocardium. Rupture of chordae tendineae and progressive annular dilation and calcification contribute to valvular regurgitation, which then places more stress on the diseased mitral valve apparatus, thereby creating a vicious circle. ECG changes (see below) and ventricular arrhythmias described in some patients with MVP appear to result from regional ventricular dysfunction related to the increased stress placed on the papillary muscles.