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Otto et al 2020 ACC/AHA Guideline for the Management of Valvular Heart Disease

February 2, 2021 Circulation. 2021;143:e72–e227. DOI: 10.1161/CIR.0000000000000923 e96

CLINICAL STATEMENTS AND GUIDELINES by afterload mismatch, survival is still improved, likely because of the reduced afterload with AVR, but improvement in LV function and resolution of symptoms might not be complete after AVR.17,23,24,56–62

3.	 Prospective clinical studies demonstrate that disease progression occurs in nearly all patients with severe asymptomatic AS. Symptom onset within 2 to 5 years is likely when aortic velocity is ≥4.0 m/s or mean pressure gradient is ≥40 mm Hg. The additive risk of AVR at the time of other cardiac surgery is less than the risk of reoperation within 5 years.12–16,63–65 4.	 Mean pressure gradient is a strong predictor of outcome after AVR, with better outcomes seen in patients with higher gradients. Outcomes are poor with severe low-gradient AS but are still better with AVR than with medical therapy in those with a low LVEF, particularly when contractile reserve is present. The document “Echocardiographic Assessment of Valve Stenosis: EAE/ASE Recommendations for Clinical Practice” defines severe AS on dobutamine stress testing as a maximum velocity >4.0 m/s with a valve area ≤1.0 cm2 at any point during the test protocol, with a maximum dobutamine dose of 20 mcg/kg per minute.66 The recommendation for AVR in these patients is based on outcome data in several prospective nonrandomized studies. LVEF typically increases by 10 LVEF units and may return to normal if afterload mismatch was the cause of LV systolic dysfunction. If dobutamine stress testing indicates moderate, not severe AS, GDMT for HF can be continued without AVR. Patients without contractile reserve may also benefit from AVR, but decisions in these high-risk patients must be individualized because outcomes are poor with either surgical or medical therapy. The role of TAVI in these patients is currently under investigation.17,22–24,59,60,67 5.	 A subset of patients with severe AS presents with symptoms and with a low velocity, low gradient, and low stroke volume index, despite a normal LVEF. Low-flow, low-gradient severe AS with preserved LVEF should be considered in patients with a severely calcified aortic valve, an aortic velocity <4.0 m/s (mean pressure gradient <40 mm Hg), and a valve area ≤1.0 cm2 when stroke volume index is <35 mL/m2. Typically, the LV is small, with thick walls, diastolic dysfunction, and a normal LVEF (≥50%). The first diagnostic step is to ensure that data were recorded and measured correctly. If hypertension is present, blood pressure is controlled before reevaluation of AS severity. Next, valve area is indexed to body size because an apparent small valve area may be only moderate AS in a small patient; an aortic valve area index ≤0.6 cm2/m2 suggests severe AS. Transaortic stroke volume is calculated by Doppler or 2D imaging. Measurement of a CT calcium score often is helpful. Evaluation for other potential causes of symptoms ensures that symptoms are most likely attributable to valve obstruction. Although the survival rate after TAVI is lower in patients with low-flow severe AS than in patients with normal-flow severe AS, AVR appears beneficial, with an increase in stroke volume and improved survival as compared with medical therapy.18,25–27,54,68–76

6.	 Exercise testing may be helpful in clarifying symptom status in patients with severe AS. When symptoms are provoked by exercise testing, the patient is considered symptomatic and meets a COR 1 recommendation for AVR; symptoms are symptoms, whether reported spontaneously by the patient or provoked on exercise testing. The rate of symptom onset within 1 to 2 years is high (about 60% to 80%) in patients without overt symptoms who demonstrate 1) a fall of ≥10 mm Hg in systolic blood pressure from baseline to peak exercise or 2) a significant decrease in exercise tolerance as compared with age and sex normal standards. Management of patients with a lack of appropriate rise in BP with exercise is less clear. Decisions about elective AVR in these patients include consideration of surgical risk, patient preferences, and clinical factors, such as age and comorbid conditions.13,28,77–82 7.	 In patients with very severe AS and an aortic velocity ≥5.0 m/s or mean pressure gradient ≥60 mm Hg, the rate of symptom onset is approximately 50% at 2 years. On multivariable analysis of a large cohort of adults with asymptomatic AS (>500 patients), an aortic velocity ≥5 m/s was associated with a >6-fold increased risk of cardiovascular mortality (hazard ratio [HR]: 6.31; 95% CI: 2.61–15.9).33 A randomized trial of SAVR versus continued surveillance showed a significant survival benefit to early surgery in patients with aortic velocity ≥4.5 m/s.31 In patients very severe asymptomatic AS and low surgical risk, a decision to proceed with AVR or continue watchful waiting takes into account patient age, avoidance of patient–prosthesis mismatch, anticoagulation issues, and patient preferences.31–33,39 8.	 An elevated serum BNP level is a marker of subclinical HF and LV decompensation. In a cohort of 387 asymptomatic adults with severe AS, elevated BNP levels were associated with an increased 5-year risk of AS-related events, with a

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