# Learning objectives

• To understand the subsets of patients with severe aortic stenosis who do not meet the classical criteria for the diagnosis
  了解不符合经典诊断标准的严重主动脉瓣狭窄患者的亚组
• To understand the investigation algorithms for these subsets
  了解这些亚组的检查方法
• 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

# LOW FLOW STATES (LOW LVOT FLOW) 低血流状态 (低 LVOT 流量)

• More challenging when AVA does not match gradient
  当主瓣面积与压差不匹配时更具挑战性

• Require further assessment and investigation
  需要进一步评估和检查

• 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

# HIGH FLOW STATES (HIGH LVOT FLOW) 高血流状态 (高 LVOT 流量)

• 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
    考虑高心输出量的原因，如发烧和贫血

• 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
  i.e.

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

  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
  低回声或严重钙化
• 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
  低或高心输出量状态
• 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
    低估会导致错误的低主瓣面积
  • 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
    如果低估会导致低流量低压差的错误诊断

• 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。

# Stages of

# Progression of VHD 瓣膜性心脏病的发展阶段

# Valvular Aortic Stenosis 主瓣狭窄的发展阶段

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.
  问号表示主动脉瓣置换术（AVR）的阶段标签或适应症，建议但未包含在指南中，需要进一步测试和验证。
• 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.
  这些低压差常常导致对疾病严重程度的低估，因此这些患者中的许多人没有接受主动脉瓣置换手术。

• 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
    由于严重的左心室肥厚，减少了左心室腔大小
  • 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
    心输出量减少和外周血压正常化
  • More AF
    房颤

• In general, this is a more advanced stage of the disease process
  总的来说，这是疾病过程的更高级阶段

  • Older; women; hypertension history; Diabetes or metabolic syndrome.
    老年；女性；高血压史；糖尿病或代谢综合征。

• 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
  • Z_VA, 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 Z_VA 瓣膜 - 动脉阻抗？

• Z_VA provides an estimate of the global haemodynamic load that results from the summation of the valvular and vascular loads.
  Z_VA 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 Z_VA 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
    以每搏输出量指数与动脉脉压之比计算全身动脉顺应性

# 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.
  在这个不断发展的领域中，仍然需要进行更多的研究。

# Stress Echocardiography

• to Differentiate True vs. Pseudo-Severe Stenosis in Paradoxical, Low-Flow, Low-Gradient AS ^[4]
  多巴酚丁胺负荷超声

$$\begin{aligned} \text { AVA }_{\text {Proj }} &=\text { AVA }_{\text {Rest }}+[\Delta \text { AVA } / \Delta Q] \times\left(250-Q_{\text {Rest }}\right) \\ &=0.71+\frac{0.06}{55} \times(250-165)=0.8 \mathrm{~cm}^{2} \end{aligned}$$

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

• Heterogeneous but commonest of low gradient group
  异质但最常见的低压差组
• Severe AS less likely
  严重的可能性较小
• More commonly female:
  女性更常见的：
  • Small body size patients; small LVOT area
    体型较小的患者；左心室流出道面积较小
  • Fluid dynamic inconsistencies in the gradient-area guideline
    梯度面积指南中的流体动力学不一致
    • 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]
  低流量状态是不良结局的独立预测因素

• 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]