# 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
Streptococcaceae 链球菌240 (48%)
Oral streptococci 口腔链球菌93 (19%)
Group D streptococci D 群链球菌62 (13%)
Pyogenic streptococci 化脓性链球菌25 (5%)
Enterococci 肠球菌52 (10%)
Other Streptococcaceae 其他链球菌8 (2%)
Staphylococcaceae 葡萄球菌180 (36%)
Staphylococcus aureus 金黄色葡萄球菌132 (27%)
Other microorganisms 其他微生物42 (9%)
≥ 2 microorganisms 合并两种微生物9 (2%)
None identified 未明确26 (5%)
  • 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

  1. Slipczuk, L., Codolosa, J. N., Davila, C. D., Romero-Corral, A., Yun, J., Pressman, G. S., & Figueredo, V. M. (2013). Infective endocarditis epidemiology over five decades: a systematic review. PloS one, 8(12), e82665. ↩︎

  2. Habib, G., Lancellotti, P., Antunes, M. J., Bongiorni, M. G., Casalta, J. P., Del Zotti, F., ... & Zamorano, J. L. (2015). 2015 ESC guidelines for the management of infective endocarditis: the task force for the management of infective endocarditis of the European Society of Cardiology (ESC) endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). European heart journal, 36(44), 3075-3128. ↩︎ ↩︎