# Complications of Infective Endocarditis — AHA 2015

## Overview

Complications of IE occur in a substantial proportion of patients and are a major determinant of morbidity and mortality. The AHA categorizes IE complications into cardiac, embolic/neurological, renal, and mycotic aneurysm-related categories. Approximately **20-50% of patients** with IE experience one or more complications during their illness.

## Cardiac Complications

### Heart Failure

- Heart failure is the **most common indication for surgery** and the strongest predictor of in-hospital mortality in IE
- Occurs in approximately **30-40%** of patients with IE
- Most frequently results from new or worsening aortic or mitral regurgitation due to valve destruction
- Management:
  - Standard heart failure medical therapy (diuretics, vasodilators) as a bridge to surgery
  - **Early surgery is recommended** (Class I, Level of Evidence B) when heart failure is caused by valve dysfunction
  - Heart failure that does not respond to medical therapy constitutes an indication for **emergent surgery**

### Paravalvular Extension (Abscess, Fistula)

- Paravalvular extension occurs in **10-40% of NVE** and is most common with aortic valve IE
- Higher incidence in **prosthetic valve IE (56-100%)**
- Manifestations include:
  - **Perivalvular abscess:** walled-off cavity adjacent to the annulus
  - **Mycotic aneurysm of the sinus of Valsalva**
  - **Intracardiac fistula:** communication between cardiac chambers or between a chamber and the pericardium
- New **atrioventricular (AV) block** or conduction disturbance in a patient with IE should raise suspicion for paravalvular abscess, especially with aortic valve involvement (Class I, Level of Evidence B)
- TEE is the diagnostic modality of choice; cardiac CT may add complementary information
- Paravalvular abscess is a **Class I indication for surgery** (Level of Evidence B)

### Conduction Abnormalities

- New conduction abnormalities (first-degree AV block, second/third-degree AV block, bundle branch block) occur in **1-15%** of patients with IE
- Most commonly associated with aortic valve IE and periannular abscess involvement of the conduction system
- ECG should be monitored **daily** in patients with aortic valve IE to detect new conduction abnormalities
- Development of new AV block in the setting of IE warrants urgent TEE and surgical consultation

## Embolic Complications

### Incidence and Risk Factors

- Embolic events occur in **20-50%** of patients with IE
- **Stroke** is the most frequent and most serious embolic complication
- Risk factors for embolization:
  - Vegetation size **> 10 mm** (particularly on the anterior mitral leaflet)
  - Vegetation mobility
  - *S. aureus* infection (higher embolic rate vs. other organisms)
  - Prior embolization (high risk of recurrence)
  - Multivalvular involvement

### Stroke and Neurological Events

- Neurological complications occur in **20-40%** of IE cases
- Types of neurological events:
  - **Ischemic stroke** (most common): from vegetation embolization to cerebral arteries
  - **Hemorrhagic stroke** (intracerebral hemorrhage): from hemorrhagic transformation of ischemic infarct, ruptured mycotic aneurysm, or erosion of septic arteritis
  - **Meningitis** (particularly with S. aureus IE)
  - **Brain abscess**
  - **Transient ischemic attack (TIA)**
- Preoperative neurological imaging (CT or MRI of the brain) is recommended for **all patients with IE** being considered for surgery (Class I, Level of Evidence B)

### Splenic Emboli and Abscess

- Splenic embolization occurs in up to **40%** of left-sided IE cases (many subclinical)
- Splenic abscess should be suspected when:
  - Persistent fever or bacteremia despite appropriate antimicrobial therapy
  - Left upper quadrant pain or tenderness
- CT abdomen with contrast is the diagnostic modality of choice
- Management options:
  - Small abscesses (< 2 cm): antimicrobial therapy alone with serial imaging
  - Larger or multiloculated abscesses: percutaneous drainage or splenectomy
  - **Splenic abscess should be treated before cardiac surgery** when possible, to reduce perioperative infection risk

### Systemic Embolization and Anticoagulation

- The rate of embolization **decreases substantially** within the first 1-2 weeks of effective antimicrobial therapy
- Anticoagulation for the sole purpose of preventing embolization in NVE is **not recommended** (Class III, Level of Evidence B)
- For patients on chronic anticoagulation for other indications (e.g., mechanical valve, atrial fibrillation):
  - If **NVE with no neurological event:** continue anticoagulation with close monitoring
  - If **S. aureus PVE:** discontinue all anticoagulation for **at least 2 weeks** after the embolic event (Class IIa, Level of Evidence C)
  - If **ischemic stroke with mechanical valve:** discontinue anticoagulation for **at least 2 weeks**, then reassess with repeat neuroimaging

## Mycotic Aneurysms

- Mycotic (infectious) aneurysms result from septic embolization to the vasa vasorum of arterial walls
- Most commonly involve **intracranial arteries** (distal branches of the middle cerebral artery)
- Also occur in the aorta, splenic, hepatic, and superior mesenteric arteries
- Estimated incidence: **2-4%** of IE patients (may be higher with systematic screening)
- Diagnosis:
  - CT angiography (CTA) or magnetic resonance angiography (MRA) for intracranial aneurysms
  - Conventional catheter angiography remains the gold standard when CTA/MRA is inconclusive
- Management decision tree:

```
Mycotic aneurysm identified
  -> Unruptured?
      -> Start/continue antimicrobial therapy
      -> Serial imaging at 2-4 week intervals
      -> Resolving? -> Continue antibiotics, monitor
      -> Enlarging or persistent? -> Endovascular or surgical intervention
  -> Ruptured?
      -> Emergent intervention (endovascular coiling or surgical clipping)
      -> Stabilize before cardiac surgery if feasible
```

- Intracranial mycotic aneurysms should be treated **before cardiac surgery** when identified, to reduce risk of intraoperative rupture during heparinization

## Renal Complications

- Renal complications occur in approximately **30%** of patients with IE
- Mechanisms include:
  - **Immune complex-mediated glomerulonephritis** (most common cause of renal injury in subacute IE)
  - **Renal infarction** from septic emboli
  - **Drug-induced nephrotoxicity** (aminoglycosides, vancomycin, contrast agents)
  - **Hemodynamic impairment** (heart failure, sepsis)
- Monitoring:
  - Serum creatinine and urinalysis should be monitored at least twice weekly
  - Aminoglycoside levels (trough < 1 mcg/mL for gentamicin) must be closely followed
  - Adjust antibiotic dosing for renal impairment (consider ampicillin + ceftriaxone over ampicillin + gentamicin for enterococcal IE when CrCl < 50 mL/min)

## Persistent Bacteremia and Treatment Failure

- Persistent bacteremia (positive blood cultures > 5-7 days after starting appropriate therapy) should prompt evaluation for:
  1. **Paravalvular abscess** (TEE recommended)
  2. **Metastatic infection** (CT of chest, abdomen, pelvis; MRI of spine if back pain)
  3. **Drug-resistant organism** (re-check susceptibilities)
  4. **Infected intravascular device** (central line, pacemaker — consider removal)
  5. **Need for surgical intervention**
- Metastatic infections include:
  - Vertebral osteomyelitis/discitis
  - Septic arthritis
  - Psoas abscess
  - Splenic abscess

## Special Population: Prosthetic Valve IE

- PVE accounts for **10-30%** of all IE cases
- **Early PVE** (within 60 days of surgery): predominantly caused by coagulase-negative staphylococci, S. aureus, and gram-negative bacilli; high mortality (40-80%)
- **Late PVE** (> 60 days after surgery): organism distribution similar to NVE
- PVE has higher rates of:
  - Paravalvular extension and abscess formation
  - Heart failure
  - Need for reoperation
  - In-hospital mortality
- Surgery is more frequently required in PVE than NVE

## Multidisciplinary Endocarditis Team

- The AHA recommends that patients with IE be managed by a **multidisciplinary team** including cardiology, cardiothoracic surgery, infectious disease, neurology, and other specialists as needed (Class I, Level of Evidence B)
- Centers with dedicated endocarditis teams have demonstrated improved outcomes, including lower in-hospital mortality
- The team should convene early in the hospital course to develop a comprehensive management plan addressing antimicrobial therapy, surgical timing, and complication management

## Limitations

- The true incidence of embolic complications may be underestimated, as many embolic events (e.g., splenic, renal) are subclinical and detected only by systematic imaging
- Anticoagulation management in the setting of IE with neurological complications is based on limited observational data and expert consensus; randomized trials are lacking
- The optimal timing of surgery after neurological events remains an area of considerable uncertainty, with recommendations based on retrospective analyses rather than prospective trials
- Mortality prediction in IE is complex; no single validated scoring system reliably guides surgical vs. medical management decisions
