Novel Frontiers for Managing Tricuspid Valve Endocarditis

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Right-sided Infective Endocarditis

Risk factors and etiology

Right-sided infective endocarditis (RSIE) accounts for ∼10% of all IE cases and continues to rise with an aging multimorbid population (1). Nearly 90% of all RSIE occurs in patients who inject drugs, 9% in patients with cardiac implantable electronic devices (CIEDs) or intravascular devices, and 1% in those with congenital heart disease (CHD) (1,2). The growing opioid epidemic, especially among younger patients, effectively doubled the rate of IE-related hospitalizations in the United States to 30% by 2015 (1). The annual incidence of IE from intravenous drug use (IVDU) is estimated to be 2%-5%, with ∼90% of patients experiencing RSIE directly involving the tricuspid valve (TV) and 10% the pulmonary valve or other structures (1,2).

Mechanisms of disease

With IVDU, several mechanisms have been proposed to contribute to RSIE. These include the co-injection of other matter (eg, talc) that result in direct endothelial damage, and the introduction of organisms on the skin, diluents, or the drug itself, directly into the bloodstream at injection sites (1, 2, 3). With CIEDs or intravascular devices, IE usually commences with contamination at implantation or handling (1, 2, 3). Staphylococcus aureus accounts for most RSIE (60%-90%), followed by Streptococcal, gram-negative, or HACEK bacteria (1, 2, 3). Whereas methicillin-sensitive S. aureus causes RSIE involving prosthetic valves or intravascular catheters, methicillin-resistant S. aureus and fungal organisms do so in the setting of IVDU or chronic alcoholism and CIEDs or immunosuppression (1, 2, 3).

Clinical presentation and diagnosis

Fever is the most common symptom of RSIE and is frequently associated with anorexia, weight loss, myalgia, breathlessness, malaise, and night sweats (1, 2, 3). Pulmonary manifestations are seen in up to 75% of patients with RSIE secondary to septic emboli, and care must be taken to not mistake pleuritic chest pain, cough, and dyspnea for lower respiratory tract infections (2,3). Clinical examination should focus not only on detecting signs of right heart involvement (tricuspid regurgitation [TR] and right heart failure [RHF]), but also left heart involvement, which can occur in 13% of patients (1, 2, 3). This should be accompanied by a systematic evaluation for metastatic infection to the brain, eyes, abdomen and spine that are commonplace in S. aureus infections (1, 2, 3). Transthoracic echocardiography is normally sufficient for identifying isolated RSIE, but transoesophageal echocardiography may be required to detect left-sided heart complications (1, 2, 3). The threshold for adjunctive imaging with computed tomography, magnetic resonance, and nuclear imaging should be low for the detection of embolic or metastatic infections (1, 2, 3). Although a diagnosis of RSIE is usually made with the use of the Duke criteria, clinicians should be aware that this approach has reduced sensitivity compared with diagnosing left-sided IE (1, 2, 3).

Therapeutic management

In RSIE, the mainstay of treatment is intravenous antibiotic therapy, the removal of intravascular devices, and surgery (1, 2, 3). Patients should ideally be managed by a specialist endocarditis team composed of microbiologists, valve disease specialists, and cardiac surgeons owing to the rapid decompensation that can occur in these patients warranting surgical intervention (1, 2, 3). The majority of patients with isolated RSIE can be managed with the use of antibiotics alone. Surgery is recommended for those with vegetation(s) >2 cm, recurrent septic emboli despite appropriate antimicrobials, persistent bacteremia, and cardiogenic or septic shock (1, 2, 3). In a 200-patient case series, 20% underwent surgery but mainly for concomitant left-sided involvement (1). The overall prognosis of medically treated RSIE is favorable with a 6% 1-year mortality, especially when related to IVDU or CIEDs versus intravascular catheters or CHD (2). In contrast to left-sided IE, heart failure is not a common surgical indication, because hemodynamic consequences of severe TR are largely well tolerated and can be successfully treated with diuretic pharmacotherapy (1, 2, 3, 4). Where surgery is required, large vegetations should be removed by vegetectomy and severe TR corrected with TV repair where possible (1, 2, 3, 4). Mechanical valves or bioprostheses are fraught with challenges associated with high-dose anticoagulation, postoperative pain control or sternal wound healing in noncompliant intravenous drug users, pacemaker insertion, and shorter-term durability predisposing to redo procedures (1, 2, 3, 4).

Given the relatively high success rates with medically managed RSIE, careful decision-making needs to occur when considering surgery. A failure of inflammatory markers to fall may simply indicate evolving lung changes secondary to index septic emboli rather than persistent bacteremia or antimicrobial failure. Furthermore, the risk of embolism falls substantially after appropriate antibiotic initiation, and centers may elect to initially adopt a conservative strategy regardless of vegetation size (1, 2, 3, 4, 5). This approach may be preferable where a patient exhibits appropriate clinical improvement with no evidence of further septic emboli and there is doubt as to TV reparability or IVDU recidivism.

Innovative percutaneous extracorporeal circuitry–based therapies

In this issue of JACC: Case Reports, Zern et al (5) report their use of the AngioVac system (AngioDynamics) in a 25-year-old woman with acquired severe TR, septic pulmonary emboli, and hypoxemia-induced cardiac arrest necessitating veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) (5). The system operates via a percutaneous veno-venous (VV) extracorporeal circuit and uses vacuum suction to remove fresh soft thrombi or emboli from the venous circulation via a 90-cm 22-F coil-reinforced dedicated drainage cannula (1,5). There are reports of its use to debulk large TV vegetations as a bail-out procedure in patients with RSIE who are otherwise too unwell for surgery (1,5), the principle being that this reduces the infectious load and risk of further embolic events and facilitates patient stabilization. Despite its appeal, global experience of the use of the vacuum-based aspiration system for this indication is limited, with a distinct lack of randomized controlled trial data supporting its use against conventional antimicrobial and surgical strategies (1).

In this case, the primary indication for the vacuum-based aspiration procedure was based on the size of the vegetation. Whether or not antimicrobial therapy alone would have resulted in a similar patient outcome remains unknown. This is relevant because the prevailing issues were refractory hypoxemia rather than cardiogenic shock, RHF, ongoing embolic events, or uncontrollable sepsis. Although vacuum-based aspiration is an attractive option for RSIE, it does carry risks of vascular, myocardial or TV injury, tamponade, and systemic embolism (1). Any consideration of its use should therefore be made by endocarditis specialist team consensus and in light of generally favorable patient outcomes with existent treatment strategies.

Zern et al (5) also reveal a dynamic approach to utilizing ECMO to optimize the patient’s oxygenation, extending our knowledge of such circuitry. The authors further demonstrate how they overcame the technical challenges of adding another venous circuit to an existing veno-arterio-venous ECMO system. The patient had cannulation of bilateral internal jugular and femoral systems to accommodate these dual circuits (5). The arterial return cannula was clamped on therapeutic anticoagulation to avoid entraining air or vegetation emboli, while elegantly illustrating the patient’s suitability for weaning off VA to VV support for hypoxemia with recovering cardiac function (5). Although the patient ultimately benefited from this combined use of the ECMO configurations and the vacuum-based aspiration system, the complex circuitry requiring multiple access sites heightened the potential risks of vascular access site bleeding, infection, limb ischemia, deconditioning, and so on (1,5).

Conclusions

RSIE has unique risk factors, etiology, clinical presentation, complications, prognosis, and therapeutic options (Figure 1, Table 1). Diagnosis still involves the Duke criteria, and imaging plays a central role in the detection of right-sided vegetations in patients presenting with a high degree of clinical suspicion. The incidence of RSIE is expected to increase with the growing epidemic of IVDU, the rise in intravascular device implantation, and the longer-term survival of patients with CHD or other chronic immunosuppressed illnesses. In cases where conservative management with intravenous antibiotics is recalcitrant and surgical risk prohibitive, novel percutaneous interventions such as the vacuum-based aspiration system may serve as therapeutic options for patients with complex TV IE. At present, there are no guidelines regarding the use of percutaneous therapeutic strategies in RSIE, so each case should be considered individually by carefully weighing the risks and benefits of the different management options. Future work is needed to evaluate the safety and efficacy of each of these therapeutic options.

Figure 1.

Diagnosis and Therapeutic Strategies of Right-Sided Infective Endocarditis

Predisposing factors for right-sided infective endocarditis (RSIE) include intravenous drug use (IVDU), the presence of cardiac implantable electronic or intravascular devices, and right-sided congenital heart disease. RSIE diagnosis relies on the clinical presentation (eg, fever, septic pulmonary emboli, etc) alongside positive blood cultures (eg, Staphylococcus aureus) and imaging evidence of right-sided vegetations predominantly involving the tricuspid valve (TV). Therapy generally requires intravenous antibiotics, source control, and surgery (eg, vegetectamy or TV repair preferable) where indicated. The percutaneous AngioVac system (AngioDynamics) may offer an alternative option where RSIE remains refractory to medical therapy and the risk for surgical intervention is prohibitive. The venous drainage cannula is outfitted with a unique funnel-shaped and 20°-angulated distal tip that aspirates thrombi or vegetative materials with the use of vacuum suction to debulk the affected structure(s). The filtered blood is then returned to the patient via its veno-venous (VV) extracorporeal circuit; this differs from extracorporeal membrane oxygenation by substitution of the oxygenator with a filter component. Risks include vascular, myocardial or TV injury, tamponade, and pulmonary embolism. RHF = right heart failure; TR = tricuspid regurgitation.

Table 1.

Risk Factors, Diagnosis and Therapeutics of Right-Sided Infective Endocarditis

Category	Relevant to Right-Sided Infective Endocarditis
Risk factors and prevention	Key RSIE risk factors: •Prior IE •IVDU •CIED or intravascular device •Congenital heart disease [if cyanotic, ≤6 months after repair with prosthetic material or lifelong if residual shunt or valve regurgitation]	Prevention strategies: •Good oral hygiene and routine check-ups •Screen nares for Staphylococcus aureus •Eliminate potential infectious sources ≥2 weeks before device implantation •Procedural antibiotic prophylaxis •Aseptic procedural techniques
Diagnostic Duke criteria	Major criteria: •Positive blood cultures for IE (2 samples drawn >12 h apart) •Positive imaging for IE (echocardiography, computed tomography, or nuclear imaging)	Minor criteria: •Predisposing risk factor (IVDU or cardiac condition) •Fever >38 °C •Vascular phenomena (septic pulmonary embolism) •Immune phenomena (very rare) •Microbiological evidence
Medical therapies	Causative organism:	First-line intravenous therapy:
	•Staphylococcus species:
	Methicillin-sensitive	Native valve: •Cloxacillin 12 g/day IV in 4-6 doses × 4-6 wk
	Methicillin-resistant	Native valve: •Vancomycin 30-60 mg/kg/day IV in 2-3 doses × 4-6 wk
	Methicillin-sensitive or resistant	Prosthetic valve: •Add to regimen above: rifampin 900-1200 mg IV in 2 or 3 divided doses ≥6 wk + gentamicin 3 mg/kg/day IV in 1 or 2 doses × 2 wk
	•Streptococcal species	•Penicillin G 12-18 million U/day IV continuous or in 4-6 doses × 4 wk or •Amoxicillin 100-200 mg/kg/day IV in 4-6 doses × 4 wk or •Ceftriaxone 2 g/day IV in 1 dose × 4 wk •In penicillin allergy: vancomycin 30 mg/kg/day IV in 2 doses × 4 wk
	•Enterococcus species	•Amoxicillin 200 mg/kg/day IV in 4-6 doses × 4-6 wk + gentamicin 3 mg/kg/day IV in 1 dose × 2-6 wk or •Ampicillin 200 mg/kg/day IV in 4-6 doses × 6 wk + ceftriaxone 4g/day IV in 2 doses × 6 wk •In penicillin allergy: vancomycin 30 mg/kg/day IV in 2 doses + gentamicin 3 mg/kg/day IV in 1 dose × 6 wk
Key surgical indications	European considerations: •Persistent fungi or bacteremia for >7 days despite adequate antimicrobials •Persistent TV vegetations >20 mm after recurrent pulmonary embolism ± RHF •RHF due to severe TR with poor diuretic response •If percutaneous extraction of CIED-related IE incomplete, impossible, or associated with severe destructive TV IE •If CIED-related IE associated with large vegetations >20 mm	U.S. considerations: • Surgery reasonable for certain complications: • Sustained infection by difficult-to-treat organisms (fungi or multidrug-resistant bacteria) • TV vegetations ≥20 mm • RHF due to severe TR with poor medical therapeutic response • Recurrent pulmonary embolism despite antimicrobials •Valve repair rather than replacement when feasible •Individualized prosthesis if valve replacement •Reasonable to avoid surgery when possible in those with IVDU

CIED = cardiac implantable electronic device; IE = infective endocarditis; IV = intravenous; IVDU = intravenous drug use; RHF = right heart failure; RSIE = right-sided infective endocarditis; TR = tricuspid regurgitation; TV = tricuspid valve.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.