# Learning objectives

  • To understand the subsets of patients with severe aortic stenosis who do not meet the classical criteria for the diagnosis
  • To understand the investigation algorithms for these subsets
  • To discuss the prognosis and surgical/interventional management of these patient sub-groups
    讨论这些亚组患者的预后和手术 / 介入治疗

# Difficult Sub-Groups DISCORDANT MEASUREMENTS 测量不一致的困难亚组


  • More challenging when AVA does not match gradient

  • Require further assessment and investigation

  • 2 distinct clinical entities are seen
    可以看到 2 个不同的临床类型

    1. Reduced LVEF 射血分数降低
      • Low Flow, Low Gradient Severe AS with impaired LVEF - discussed in Aortic Stenosis lecture
        低血流、低压差与左心室射血分数受损的重度 AS
      • Pseudo-severe AS
        假性重度 AS
    2. Normal EF 射血分数正常
      • Paradoxical Low Flow Low Gradient Severe AS (normal EF)
        矛盾的低流量低压差的严重 AS(正常 EF)
      • Normal flow Low Gradient Severe AS
        正常流量、低压差的严重 AS


  • Valve area may be > 1.0 cm despite a peak velocity > 4 m/s and mean gradient > 40 mmHg in the presence of a HIGH trans-valvular flow
    尽管峰值速度大于 4 m/s,平均跨瓣压差大于 40 mmHg,但在高跨瓣流量情况下,瓣膜面积可能大于 1.0 cm

    • AR? 主动脉瓣反流
    • Consider causes of high CO, such as fever and anaemia
  • Usually, the haemodynamics of gradient and velocities would be consistent with significant AS in these situations
    通常,在这些情况下,压差和速度的血流动力学与显著的 AS 一致

  • Need to account for V1 in the Bernoulli equation when V1 > 1.5ms-1
    当 V1 > 1.5ms-1 时,需要在伯努利方程中考虑 V1

    P1P2=4(V22V12)P_{1} - P_{2} = 4(V_{2}^{2}- V_{1}^{2})

    V1 = proximal velocity (peak LVOT) 近端血流速度 (LVOT 峰值)
    and V2 = distal velocity 远端速度

# Discrepancies in the values obtained 测量值存在差异时

# Measurement taken are incorrect/inaccurate 需要考虑测量结果不正确 / 不准确的情况

  • Low echogenicity or severe calcifications
  • AF - beat to beat variation
    房颤 - 每次搏动之间的变化
  • Sub-aortic stenosis - makes the LVOT velocity incorrect
    主动脉瓣下狭窄 - 使 LVOT 速度不正确
  • Low or high Cardiac output states
  • Difficult LVOT measurements
    LVOT 测量困难

# Critical Issues 关键问题

  • LVOT diameter incorrect:LVOT 直径不正确

    • Underestimation leads to falsely low AVA
    • Discussed in Aortic Stenosis lecture
  • LVOT velocities incorrect: LVOT 速度不正确

    • Sub-aortic pathologies 主动脉瓣下病变
    • If underestimated can lead to a false diagnosis of low flow low gradient AS
  • Recheck LVOT measurement 重新检查 LVOT 测量

  • Perform TOE for LVOT measurement 使用经食道超声测量

  • Consider CT scan or invasive catheterisation as alternative assessment technique.
    考虑将 CT 扫描或有创插管作为替代评估技术。

Low gradientHigh Gradient

Normal flow
Stroke volume index > 35 ml/m2

"Normal Flow - Low Gradient Severe AS and preserved EF" NF/LG
"Ensure not moderate AS"

Classical Severe Aortic Stenosis

Low flow
Stroke volume index < 35 ml/m2

Severe AS with normal EF
"Paradoxical Low Flow-Low Gradient AS" LF/LG
Or "Ensure not pseudo-severe LF/LG AS"

Severe Aortic Stenosis with Low flow

# Stages of

# Progression of VHD 瓣膜性心脏病的发展阶段



At risk

Patients with risk factors for the development of VHD
伴有 VHD 发生危险因素的患者



Patients with progressive VHD (mild-to-moderate severity and asymptomatic)
进行性 VHD 患者 (轻度至中度严重且无症状)


Asymptomatic severe 无症状重症

Asymptomatic patients who have reached the criteria for severe VHD
达到严重 VHD 标准的无症状患者

  • C1: Asymptomatic patients with severe VHD in whom the left or right ventricle remains compensated
    无症状的重度 VHD 患者,其左或右心室仍处于代偿状态
  • C2: Asymptomatic patients who have severe VHD, with decompensation of the left or right ventricle
    患有严重 VHD 的无症状患者,左室或右室失代偿


Symptomatic severe 有症状重症

Patients who have developed symptoms as a result of VHD
因 VHD 而出现症状的患者

# Valvular Aortic Stenosis 主瓣狭窄的发展阶段

StageDefinitionValve AnatomyValve HemodynamicsHemodynamic ConsequencesSymptoms


At risk of AS

  • Bicuspid aortic valve (pr other congenital valve anomaly)
  • Aortic valve sclerosis 主动脉瓣硬化
  • Aortic Vmax < 2 m/s
  • None
  • None


Progressive AS

  • Mild-to-moderate leaflet calcification of a bicuspid or trileaflet valve with some reduction in systolic motion or
  • Rheumatic valve changes with commissural fusion
  • Mild AS: Aortic Vmax 2.0-2.9 m/s or mean △P < 20 mmHg
  • Moderate AS: Aortic Vmax 3.0-3.9m/s or mean △P 20-39 mmHg
  • Early LV diastolic dysfunction may be present
  • Normal LVEF
  • None
C - Asymptomatic severe AS 无症状重度 AS


Asymptomatic severe AS

  • Severe leaflet calcification or congenital stenosis with severely reduced leaflet opening
  • Aortic Vmax ≥ 4 m/s or mean △P ≥ 40 mmHg

  • AVA typically is ≤ 1 cm2 (or AVAi ≤ 0.6 cm2/m2)

  • Very severe AS is an aortic Vmax ≥ 5 m/s, or mean △P ≥ 60 mmHg

  • LV diastolic dysfunction
    LV 舒张功能障碍
  • Mild LV hypertrophy 轻度左心室肥厚
  • Normal LVEF 正常射血分数
  • None - exercise testing is reasonable to confirm symptom status
    无 - 运动测试是确认症状状态的合理方法


Asymptomatic severe AS with LV dysfunction
无症状重度 AS 伴左心功能不全

  • Severe leaflet calcification or congenital stenosis with severely reduced leaflet opening
  • Aortic Vmax ≤ 4 m/s or mean △P ≥ 40 mmHg
  • AVA typically is ≤ 1 cm2 (or AVAi ≤ 0.6 cm2/m2)
  • LVEF < 50%
  • None
D - Symptomatic severe AS 症状性重度 AS


Symptomatic severe high-gradient AS
症状性重度高压差 AS

  • Severe leaflet calcification or congenital stenosis with severely reduced leaflet opening
  • Aortic Vmax ≥ 4 m/s, or mean △P ≥ 40 mmHg
  • AVA typically is ≤ 1 cm2 (or AVAi ≤ 0.6 cm2/m2), but may be larger with mixed AS/AR
    但混合 AS/AR 可能更大
  • LV diastolic dysfunction
  • LV hypertrophy
  • Pulmonary hypertension may be present
  • Exertional dyspnea or decreased exercise tolerance
  • Exertional angina
  • Exertional syncope or presyncope


Symptomatic severe low-flow/low-gradient AS with reduced LVEF
有症状的严重低血流 / 低梯度,如左心室射血分数降低

  • Severe leaflet calcification with severely reduced leaflet motion
  • AVA ≤ 1 cm2 with resting aortic Vmax < 4 m/s or mean △P < 40 mmHg
  • Dobutamine stress echo shows AVA ≤ 1 cm2 with Vmax ≥ 4 m/s at any flow rate
  • LV diastolic dysfunction
  • LV hypertrophy
  • LVEF <50%
  • HF
  • Angina 心绞痛
  • Syncope or presyncope 晕厥或近似晕厥


Symptomatic severe low-gradient AS with normal LVEF or paradoxical low-flow severe AS
有症状的重度低压差伴正常的 LVEF 或反常的低流量重度 AS

  • Severe leaflet calcification with severely reduced leaflet motion
  • AVA ≤ 1 cm2 with aortic Vmax < 4 m/s, or mean △P < 40 mmHg
  • Indexed ANA <0.6 cm2/m2 and
  • Stroke volume index < 35 mL/m2
  • Measured when the patient is normotensive (systolic BP < 140 mmHg) 当患者血压正常时测量 (收缩压 <140 mmHg)
  • Increased LV relative wall thickness LV 相对壁厚增加

  • Small LV chamber with low-stroke volume 低每搏输出量的小型 LV 腔

  • Restrictive diastolic filling 限制性舒张期充盈

  • LVEF ≥ 50%

  • HF
  • Angina
  • Syncope or presyncope

Classification and Characterisation of the Different Types of AS According to AVA, Gradient, LVEF, and Flow [1]
根据 AVA、压差、LVEF 和血流对不同类型 AS 的分类和特征

  • Classification of types of AS, including only the categories associated with symptoms and/or depressed LVEF.
    AS 类型的分类,仅包括与症状和 / 或左心室射血分数降低相关的类别。
  • It does not include stage C1 (i.e., patients with high-gradient AS, no symptoms, and preserved LVEF).
    不包括 C1 期 (即高阶梯度型 AS 患者,无症状,左心室射血分数保留)
  • Question mark indicates stage labels or indications for aortic valve replacement (AVR) that are proposed but are not included in the guidelines and will need to be further tested and validated.
  • AVAi, Indexed AVA 主动脉瓣面积指数;MG, mean gradient; RCT, randomized controlled trial; SVi, stroke volume index.

# Paradoxical Low Flow-Low Gradient Severe Aortic Stenosis 矛盾性 LFLG AS

  • Some patients with severe aortic stenosis based on valve area have a lower-than-expected gradient (e.g. mean gradient < 30 mmHg) despite preserved ejection fraction (e.g. EF > 50%)
    尽管射血分数维持正常(如 EF>50%),一些严重主动脉瓣狭窄的患者的跨瓣压差低于预期(如平均压差 < 30 mmHg)

  • Up to 35% of patients with severe aortic stenosis present with low flow, low gradient; 5% to 15% of AS patient have paradoxical LF/LG
    高达 35% 的重度主动脉狭窄患者表现为低流量、低压差;5% 至 15% 的 AS 患者存在矛盾性的 LF/LG

  • These low gradients often lead to an underestimation ol the severity of the disease, so many of these patients do not undergo surgical aortic valve replacement.

  • How is this possible? 为何会如此

    • High global afterload - Especially elderly with reduced systemic arterial compliance. HYPERTENSION
      整体后负荷高 - 尤其是全身动脉顺应性降低的老年人。高血压
    • LV longitudinal dysfunction despite normal LVEF
      尽管 LVEF 正常,但左室纵向功能障碍
    • Diastolic dlysfunction - especially restrictive physiology
      左室舒张功能 - 特别是限制性生理学
    • Reduced LV cavity size due to severe LVH
    • Higher LV mass than NF/HG (concentric hypertrophy)
      左心室质量高于 正常血流 / 高跨瓣压差 (向心性肥厚)
    • Reduced cardiac output and normalisation of peripheral blood pressure
    • More AF
  • In general, this is a more advanced stage of the disease process

    • Older; women; hypertension history; Diabetes or metabolic syndrome.
  • AS in patients with normal LVEF Low Flow Low Gradient AS relatively uncommon [2] (高压差 76%,低血流低压差占 9%,正常血流低压差占 15%)

# Echo Doppler Features of Paradoxical Low-Flow, Low-Gradient AS 超声表现

  • The Aortic Valve: 主瓣本身 [3]

    • AVA, aortic valve area 主动脉瓣面积 < 1.0 cm2
    • AVAi, aortic valve area index 主动脉瓣面积指数 < 0.6 cm2/m2
    • DVI, Doppler Velocity Index 多普勒速度指数 < 0.25
    • Severely thickened/calcified valve 严重增厚 / 钙化瓣膜
    • MG, mean gradient 平均跨瓣压差 < 40 mmHg
    • ZVA, Valvulo-arterial impedance 瓣膜动脉阻抗 ≥ 4.5
  • The Left Ventricle: 左室腔

    • EDD 舒张末内径 < 47 mm
    • EDV 舒张末容积 < 55 mL/m2
    • RWT ratio 相对室壁厚度 > 0.50
    • Myocardial fibrosis 心肌纤维化
    • Impaired LV filling 左室充盈受损
    • LVEF > 50%
    • GLS 整体应变率 ≤ 15%
    • SVi, stroke volume index 每搏量指数 < 35mL/m2

# What is Valvulo-Arterial Impedance ZVA 瓣膜 - 动脉阻抗?

  • ZVA provides an estimate of the global haemodynamic load that results from the summation of the valvular and vascular loads.
    ZVA 提供了由瓣膜和血管负荷之和产生的整体血流动力学负荷的估计值

  • Influenced by: 受到以下影响

    • Stenosis severity 狭窄的严重程度
    • Volume flow rate 容积血流率
    • Body size 身体大小
    • Systemic vascular resistance 全身血管阻力
  • Measuring ZVA in Aortic Stenosis

    • LVSP, left ventricular systolic pressure 左室收缩压
    • SVi, stroke volume index 每搏量指数
    • SAP, systolic aortic pressure 主动脉收缩压
    • MG, mean gradient 平均跨瓣压差
    • Systemic arterial compliance calculated as the ratio of stroke volume index to arterial pulse pressure
> 3.5Moderate
≥ 4.5Severe

# Ensure this is not just moderate AS 确保这不仅仅是中度 AS

  • i.e. not pseudo-severe LF/LG AS
    比如不是假性重症 LF/LG AS
  • 33% of these patients may be pseudo severe
    33% 的患者可能为假性重症
  • Like low gradient low EF patients useful ways to investigate are:
    像低压差低 EF 患者一样,有用的检查方法有:
    • Dobutamine infusion - LESS VALIDATED - only 1 study
      多巴酚丁胺注射 - 验证较少
    • CT calcium scoring CT 钙化评分
  • Additional studies still needed in this evolving field.

# Stress Echocardiography

  • to Differentiate True vs. Pseudo-Severe Stenosis in Paradoxical, Low-Flow, Low-Gradient AS [4]

AVAProj=AVARest+[ΔAVA/ΔQ]×(250QRest)=0.71+0.0655×(250165)=0.8cm2\begin{aligned} \text { AVA }_{\text {Proj }} &=\text { AVA }_{\text {Rest }}+[\Delta \text { AVA } / \Delta Q] \times\left(250-Q_{\text {Rest }}\right) \\ &=0.71+\frac{0.06}{55} \times(250-165)=0.8 \mathrm{~cm}^{2} \end{aligned}

# Normal Flow-Low Gradient Group 正常血流低压差组

  • Heterogeneous but commonest of low gradient group
  • Severe AS less likely
  • More commonly female:
    • Small body size patients; small LVOT area
    • Fluid dynamic inconsistencies in the gradient-area guideline
      • 40mmHg mean gradient cut-off may be too high??
        40mmHg 平均压差作为分界可能太高??
    • AF/ prolonged LV ejection time
      房颤 / 左室射血时间延长
  • Many (50%) will have moderate AS
    许多 (50%) 有中度 AS
  • Less severe AS/ less advanced disease state
    不太严重的 AS / 不太严重的疾病状态
  • Consider further tests if AVA < 0.6 cm2
    如果 AVA < 0.6 cm2,请考虑进一步检查
    • i.e., with more stringent criteria for severe AS.
      对严重 AS 有更严格的标准。
    • LVEF ≥ 50%, a normal flow state (stroke volume index 235 ml/m2), an AVA ≤1.0 cm2, an indexed AVA ≤ 0.6 cm2/m2, and a mean gradient < 40 mmHg
  • if AVA < 0.6 cm2 then consider
    • DSE 多巴酚丁胺负荷超声心动图
    • CT calcium scoring CT 钙化评分
    • Patients with true severe AS NF/LG group benefit from surgery.
      真正重度 AS 组的患者可从手术中获益

# LF/HG Group 低血流高压差组

  • LF is affected by high body surface area and excess weight
    LF 受到高体表面积和超重的影响
  • obesity (c. 80% obese) 肥胖 80% 存在 [5]
    • i.e. absolute stroke volume(SV) is normal, but high BSA leads to low stroke volume index(SVi)
      绝对每搏量是正常的,但高 BSA 会导致低每搏量指数
  • Higher mortality compared to NF/HG perhaps related to these comorbidities:
    与 NF/HG 相比,死亡率更高可能与这些合并症有关:
    • Obesity 肥胖
    • DM 糖尿病
    • AF 房颤
    • Heart failure presentations 心力衰竭表现

# Prognosis-medical management 预后 - 医疗管理

  • AVR was beneficial in both LF and NF groups [6]
    不管是低血流还是正常血流,主动脉瓣置换都可以使重度 AS 受益

  • Low flow states are an independent predictor of poor outcome [5:1]

  • Independent of gradient or LVEF
    与压差或 LVEF 无关

  • LF/LG worst outcome 3.2x increase mortality compared to NF/LG
    与 NF/LG 相比,LF/LG 最差结局死亡率增加 3.2 倍

  • Partner 1 cohort B (non-operable): TAVI resulted in large benefit for these LF/LG patient survival
    TAVI 为这些 LF/LG 患者的生存带来了巨大的好处
  • TAVI Treatment Comparison in LF, LEF, and LG (both cohorts)
  • Summary ot Recommendations for AS: Timing of Intervention [7] 干预时机

    AVR is reasonable in symptomatic patients who have low-flow/low-gradient severe AS (stage D3) who are normotensive and have an LVEF ≥50% if clinical, hemodynamic, and anatomic data support valve obstruction as the most likely cause of symptoms
    如果临床、血液动力学和解剖学数据支持瓣膜阻塞是最常见的症状原因,AVR 对低流量 / 低压差严重 AS(D3 阶段)有正常血压且 LVEF≥50% 的有症状患者来说是合理的

  • Algorithm for the Management of Low-Gradient AS [4:1]

  1. Hahn, R. T., Nicoara, A., Kapadia, S., Svensson, L., & Martin, R. (2018). Echocardiographic Imaging for Transcatheter Aortic Valve Replacement. Journal of the American Society of Echocardiography, 31(4), 405–433. ↩︎

  2. Adda, J., Mielot, C., Giorgi, R., Cransac, F., Zirphile, X., Donal, E., Sportouch-Dukhan, C., Réant, P., Laffitte, S., Cade, S., Le Dolley, Y., Thuny, F., Touboul, N., Lavoute, C., Avierinos, J. F., Lancellotti, P., & Habib, G. (2012). Low-flow, low-gradient severe aortic stenosis despite normal ejection fraction is associated with severe left ventricular dysfunction as assessed by speckle-tracking echocardiography: a multicenter study. Circulation. Cardiovascular imaging, 5(1), 27–35. ↩︎

  3. Pibarot, P., & Dumesnil, J. G. (2011). Paradoxical low-flow, low-gradient aortic stenosis adding new pieces to the puzzle. Journal of the American College of Cardiology, 58(4), 413–415. ↩︎

  4. Clavel, M. A., Ennezat, P. V., Maréchaux, S., Dumesnil, J. G., Capoulade, R., Hachicha, Z., Mathieu, P., Bellouin, A., Bergeron, S., Meimoun, P., Arsenault, M., Le Tourneau, T., Pasquet, A., Couture, C., & Pibarot, P. (2013). Stress echocardiography to assess stenosis severity and predict outcome in patients with paradoxical low-flow, low-gradient aortic stenosis and preserved LVEF. JACC. Cardiovascular imaging, 6(2), 175–183. ↩︎ ↩︎

  5. Eleid, M. F., Sorajja, P., Michelena, H. I., Malouf, J. F., Scott, C. G., & Pellikka, P. A. (2013). Flow-gradient patterns in severe aortic stenosis with preserved ejection fraction: clinical characteristics and predictors of survival. Circulation, 128(16), 1781–1789. ↩︎ ↩︎

  6. Ozkan, A., Hachamovitch, R., Kapadia, S. R., Tuzcu, E. M., & Marwick, T. H. (2013). Impact of aortic valve replacement on outcome of symptomatic patients with severe aortic stenosis with low gradient and preserved left ventricular ejection fraction. Circulation, 128(6), 622–631. ↩︎

  7. Nishimura, R. A., Otto, C. M., Bonow, R. O., Carabello, B. A., Erwin, J. P., 3rd, Guyton, R. A., O'Gara, P. T., Ruiz, C. E., Skubas, N. J., Sorajja, P., Sundt, T. M., 3rd, Thomas, J. D., & ACC/AHA Task Force Members (2014). 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation, 129(23), 2440–2492. ↩︎