# Learning objectives

• Definition 定义
• Diagnosis 诊断
• Diagnostic echocardiography criteria 超声诊断标准
• Echocardiographic estimation of outcome 超声对预后的评估
• Intracardiac complications of endocarditis 心内膜炎的心内并发症
• Prosthetic valve endocarditis 人工瓣膜心内膜炎
• Treatment: Medical and surgical 治疗：药物和手术

# Definition

• Infection of the endocardial surface of the heart characterised by:
  心脏心内膜表面感染的特征是：
  • Colonisation or invasion of the heart valves (native or prosthetic) or the mural endocardium by a microbe
    微生物对心脏瓣膜 (天然的或人工的) 或心内膜的定植或侵入
  • Leading to formation of bulky, friable vegetation composed of thrombotic debris and organisms
    导致形成由血栓碎片和生物体组成的笨重、易碎的赘生物
  • Often associated with destruction of underlying cardiac tissue.
    通常与潜在心脏组织的破坏有关

# Background

• A rare disease with an increase incidence up to 11 episodes/100 000 persons a year
  一种罕见疾病，发病率每年增加 11 次 / 10 万人
• High mortality disease: 15-30% 高死亡率疾病
• Poor prognosis 预后不良
• The diagnosis remains difficult 诊断仍然很困难

# Epidemiology 流行病学

• An increase in incidence
  发病率增加
• Older patients 老年患者
• Shift from streptococci to staphylococci 从链球菌转移到葡萄球菌
• Without any history of valvular disease (53% of patients with IE). 没有任何瓣膜疾病史（占 IE 患者的 53%）。

# Diagnosis 诊断

# Duke Criteria Duke 标准

# Major criteria

• Positive blood culture 血培养阳性

  • Typical organism from two cultures 两种典型菌
  • Persistent positive blood cultures taken > 12hrs apart
    间隔 > 12 小时持续
  • Three or more positive cultures taken over > 1hr
    三种或三种以上血培养阳性时间超过 1 小时

• Endocardial involvement 心内膜受累

  • Positive echocardiographic findings of vegetations
    超声心动图赘生物阳性结果
  • New valvular regurgitation
    新出现的瓣膜返流

# Minor criteria

• Predisposing valvular or cardiac abnormality
  易感瓣膜或心脏异常
• Intravenous drug misuse
  滥用静脉药物
• Pyrexia ≥ 38 °C 高热
• Embolic phenomenon 栓塞现象
• Vasculitic phenomenon 血管炎现象
• Blood cultures suggestive: organism grown but not achieving major criteria
  血液培养提示：细菌生长但未达到主要标准
• Suggestive echocardiographic findings
  超声心动图有所发现

# Duke Criteria

• 1994 a group at Duke University standardised criteria for assessing patients with suspected endocarditis

• Definite 确诊

  • 2 major criteria
  • 1 major and 3 minor criteria
    -5 minor criteria
  • pathology/histology findings 病理学 / 组织学发现

• Possible 可能

  • 1 major and 1 minor criteria
  • 3 minor criteria

• Rejected 排除

  • firm alternate diagnosis 明确的替代诊断
  • resolution of manifestations of IE with 4 days antimicrobial therapy or less
    用 4 天或更短的抗菌治疗即可消除 IE 症状

# Clinical features

• Regurgitation murmur 反流杂音（新出现的）
• Vascular symptoms 脉管症状
• Immune symptoms 免疫症状

• Minor criteria
  1. Predisposition such as predisposing heart condition, or injection drug use.
     易感因素，如易患心脏病或注射药物。
  2. Fever defined as temperature >38°C.
     发烧定义为体温
  3. Vascular phenomena (including those detected by imaging only): major arterial emboli, septic pulmonary infarcts, infectious (mycotic) aneurysm, intracranial haemorrhage, conjunctival haemorrhages, and Janeway's lesions.
     血管现象（包括仅通过影像检查发现的血管现象）：主要动脉血栓、感染性肺梗塞、感染性（真菌性）动脉瘤、颅内出血、结膜出血和 Janeway 病变。
  4. Immunological phenomena: glomerulonephritis, Osler's nodes, Roths spots, and rheumatoid factor
     免疫学现象：肾小球肾炎，奥斯勒氏结节，罗斯斑点和类风湿因子
  5. Microbiological evidence: positive blood culture but does not meet a major criterion as noted above or serological evidence of active infection with organism consistent with IE.
     微生物学证据：血液培养呈阳性，但不符合上述主要标准，或血清学证据表明与 IE 一致的病原菌存在活动感染。

# Typical organisms: Blood culture

• Microbiology of Infective Endocarditis. ^[1]
  感染性心内膜炎的微生物学

• Increased prevalence of staphylococci IE
  葡萄球菌 IE 患病率上升

# Imaging

• TTE and TOE are the first line imaging for the diagnosis of IE
  TTE 和 TOE 是诊断 IE 的一线影像学检查

• Limitations of TTE: 经胸超声的局限性

  • Underestimates size and complexity of large vegetations
    低估了大型赘生物的大小和复杂性
  • May fail to detect small vegetations(< 3 mm).
    可能无法检测到微小的赘生物 (<3 毫米)。

• Goals of Echo in IE: 超声目标

  • Identify, localise and characterise masses consistent with vegetation
    识别、定位和描述与赘生物一致的团块
  • Identify new valvular regurgitation
    确定到有新的瓣膜反流
  • Examine prosthetic valve stability
    检查人工瓣膜的稳定性
  • Apply criteria to judge prognosis once vegetation identified.
    一旦发现赘生物，应用测量尺寸等标准来判断预后。

# Accuracy of Imaging

• Sensitivity = 70% for native valve and 50% for prosthetic valve with TTE, and 96% and 92% for TOE ^[2]
  敏感性 - TTE 自体瓣膜 70%，人工瓣膜 50%，TOE 分版为 96% 和 92%
• Specificity = 90% for both TTE and TOE
  特异性 - 均为 90%
• BUT NOT 100%.

可能需要其他手段，比如 PET/CT；脑补 MR 看有没有脑梗的表现

# Diagnostic Echo Criteria 诊断超声标准

• Characteristics of mass likely to be vegetation:
  团块可能是赘生物的特征：
  • Texture: Grey scale and reflectance of myocardium
    纹理：类似心肌的灰度和反射率
  • Location: Upstream side of valve in path of jet or on prosthetic material
    位置：射流路径或人工瓣膜的上游侧
  • Motion: Chaotic and orbiting, independent of valve motion
    活动度：混沌和轨道运动，与瓣膜运动无关
    • Prolapse into upstream chamber (i.e. MV mass into LA in systole
      脱垂进入上游腔室 (例如收缩期进入 LA 的 MV 团块；主动脉瓣的赘生物一般长在左室侧，如果足够的长有可能在收缩期进入主动脉，舒张期再进入左室）
  • Shape: Lobulated, amorphous
    形状：叶片状，无固定形态
  • Accompanying abnormalities: 伴随异常
    • Abscess, fistula, new regurgitant lesion, paravalvular leak.
      脓肿、瘘管、新的反流性病变、瓣周漏。

• Characteristics of mass Inlikely to be vegetation：
  不太可能是赘生物的团块特征：
  • Texture: Reflectance myocardium or pericardium (white)
    纹理：高于心肌或心包的亮度 (白色)
  • Location: Outflow tract attachment, downstream surface of valve
    位置：附着在流出道，瓣膜下游表面
  • Shape: Stringy or hair-like strands with narrow attachment
    形状：线状的或毛发状的，狭窄的附着物
  • Lack of accompanying turbulent flow or regurgitation.
    没有伴随的湍急流动或反流

• False Positives 假阳性
  • Most common on TEE 在 TEE 上最常见的
  • Lambl's excrescences Lambl 赘生物
  • Strands on sewing rings of prosthetics
    假体瓣膜缝纫环上的线
  • Free suture 游离缝合线
  • Redundant chordae 多余的腱索
  • Chiari's remnant in RA 残留在 RA 的 Chiari 网
  • All of above tend to be highly reflective with echodensity similar to pericardiun Or aortic root. Dense, fibrotic and non-vibratoi
    以上所有这些都具有高度反射性，回声密度类似于心包或主动脉根部。致密、纤维化且无振动

• False Negatives 假阴性
  • TTE > TOE
  • High sensitivity of TOE (92-94%)
    经食道超声灵敏度更高
  • Cannot definitively rule out endocarditis
    不能明确排除心内膜炎
  • Low likelihood of IE, if negative TOE in intermediate probability patient
    如果中危患者 TOE 检查为阴性，发生 IE 的可能性低
  • In patients at high risk for IE (prosthetic valve, unexplained bacteraemia), repeat examination reasonable.
    对于 IE 高危患者（有假体瓣膜、不明原因的菌血症），重复检查是合理的。

# Multimodality imaging 多模态成像

• CT Scan

  • Diagnosis (vegetation, abscess, pseudoaneurysm)
    诊断（赘生物、脓肿、假性动脉瘤）
  • Embolic lesions
    栓塞性病变

• MRI

  • Embolic lesions, especially cerebral complications.
    栓塞性病变，尤其是脑部并发症

• PET CT scan

  • Better sensitivity for the detection of prosthetic IE
    假体瓣膜 IE 的检测灵敏度较高
  • Sens 97%, Spec 80%.

# Echo Estimation of Outcome 超声预估预后

• Size of vegetation most powerful predictor of Clinical complications (drug failure, new CHF, embolisation, surgery)
  赘生物的大小是临床并发症 (药物失效、新发心力衰竭、栓塞、手术) 最有力的预测因素，因此一定要测赘生物的大小
  • 10% in 6 mm vegetation, 50% if 11 mm and almost 100% if 16 mm
    6mm 的赘生物约 10% 发生，11mm 的赘生物则为 50%，16mm 的赘生物几乎 100%
• Complication more frequent with higher grades of mobility and lesion extent
  活动度越高，病变范围越大，并发症越多
• Vegetation consistency does not predict complications (except for calcifed lesions which has no associated complications)
  赘生物的连贯性不能预测并发症（钙化病变除外，钙化病变没有相关并发症）
• Echo predictors still apply after initiation of antibiotics.
  在开始使用抗生素后，超声预测仍然适用。

# Intracardiac Complications 心内并发症

• Valvular regurgitation 瓣膜反流
  
• Secondary infection of other valves 其他瓣膜继发感染
• Leaflet perforation 瓣叶穿孔，穿孔个数
• Perivalvulal abscess or fistula: 瓣周脓肿或瘘管
  • Abscess most likely with staph aureus 脓肿很可能与金黄色葡萄球菌有关
  • Abscess formation --> increase in morbidity and mortality.
    脓肿形成 --> 发病率和死亡率增加

# Right Sided Endocarditis 右侧心内膜炎

• Tricuspid valve vegetation most common in IV drug users
  三尖瓣赘生物最常见于静脉药物成瘾者

• Mostly caused by staph aureus
  多由金黄色葡萄球菌引起

• Pacemaker Associated Endocarditis 起搏器相关性心内膜炎

  • More leads than ever being placed
    导线放置过多
  • Symptoms are vague - mimic pneumonia
    症状模糊，类似肺炎
  • Look for vegetations along wires
    沿着导线寻找赘生物
  • Vegetations are mobile
    赘生物是可移动的
  • Thrombus and masses may look similar
    血栓和肿块可能看起来很相似
  • Treatment: Abx, removal, variable
    治疗：抗生素，去除，可变

# Prosthetic Valve Endocarditis 人工瓣膜心内膜炎

• Findings suggestive of IE in prosthetic valves:
  发现人工瓣膜中存在 IE：
  • Vegetation 赘生物
  • Valve rocking suggesting valve dehiscence
    瓣膜摇晃提示瓣膜裂开
  • Perivalvular regurgitation/abscess
    瓣周反流 / 脓肿
  • Impaired leaflet motion
    瓣叶运动受损
  • Must compare to prior
    必须与之前进行比较
• Echo evaluation limited prosthetic shadow
  回声评估有限由于假体阴影
• Low threshold to use TOE.
  经食道超声使用低阈值

# Management 管理

# Prophylaxis 预防

• Only for patients at highest risk of IE
  仅适用于 IE 风险最高的患者
  

• Antibiotic prophylaxis for dental procedures requiring manipulation of the gingival tissue or perforation of the oral mucosa
  用于需要操作牙龈组织或口腔粘膜穿孔的牙科手术的抗生素预防，

• Antibiotic: Amoxicillin or ampicillin if no allergy, clindamycin if allergy.
  抗生素：如果没有过敏，选择阿莫西林或氨苄西林，如果过敏，选择克林霉素。

# Surgery

• Surgery: To prevent or treat life threatening complications
  预防或治疗危及生命的并发症

  • Heart failure (30-40%) due to acute valve regurgitation
    急性瓣膜反流引起的心力衰竭 (30-40%)
    • Reduced mortality after surgery
      术后死亡率降低

• Systemic embolism (20% with clinical manifestations)
  系全身性栓塞（20% 有临床表现）

• Uncontrolled infection (10-20% 不受控制的感染

  • Higher mortality, higher rate of complications (conduction disorder, peri operative mortality, need of a second surgery).
    更高的死亡率，更高的并发症发生率 (传导障碍，围手术期死亡率，需要第二次手术)。

• Indications and Timing of Surgery ^[2]

  • HACEK = Haemophilus parainfluenzae, Haemophilus aphrophilus, Haemophilus paraphrophilus, Haemophilus influenzae, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae and Kingella denitrificans; HF = heart failure; IE = infective endocarditis; NVE = native valve endocarditis; PVE = prosthetic valve endocarditis.
    HACEK = 副流感嗜血杆菌、嗜人嗜血杆菌、副嗜血杆菌、流感嗜血杆菌、伴生放线杆菌、人心脏杆菌、腐蚀性艾肯氏杆菌、金黄色葡萄球菌和脱氮金黄色葡萄球菌；HF = 心力衰竭；IE = 感染性心内膜炎；NVE = 自体瓣膜心内膜炎；PVE = 人工瓣膜心内膜炎。
  • a, Emergency surgery: surgery performed within 24 h; urgent surgery: within a few days; elective surgery: after at least 1–2 weeks of antibiotic therapy.
    急诊手术：24 小时内手术；紧急手术：几天内；择期手术：抗生素治疗至少 1-2 周后。
  • b, Class of recommendation.
  • c, Level of evidence.
  • d, Reference(s) supporting recommendations.
  • e, Surgery may be preferred if a procedure preserving the native valve is feasible.
    如果保存原生瓣膜的程序可行，手术可能是首选。

# Infective Endocarditis TEAM

• IE is NOT a single disease
  IE 不是一种单一的疾病
• High level of suspicious is needed
  需要高度的可疑
• High level of expertise
  高水平的专业知识
• Early discussion with surgery team
  与外科团队进行早期讨论
• The prognosis depends on an early management
  预后取决于早期治疗