**2. Right sided infective endocarditis**

Right sided Infective Endocarditis (RSIE) accounts for about 10% of all IE cases [6]. Typically, these patients are younger with fewer medical comorbidities and less underlying valve disease as compared to patients with left-sided IE [6]. RSIE involves both tricuspid valve endocarditis (TVE) and cardiac implantable device endocarditis (CIDE). RSIE is most frequently seen with intravenous drug use (IVDU). Other predisposing risk factors include use of central venous catheters, cardiovascular implanted electronic devices, congenital heart disease, prosthetic heart valves, and end-stage renal disease on hemodialysis [5, 6]. Mortality rate of RSIE is typically 5–15% [6]. The risk factors and independent predictors of death are age, *Staphylococcus aureus* infection, heart failure, embolic events and health care-associated IE [5].

### **2.1 Tricuspid valve endocarditis**

#### *2.1.1 Epidemiology*

Ninety percent of RSIE involves the tricuspid valve, of which infection resulting from intravenous drug use (IVDU) constitutes approximately 30–40% of all tricuspid valve endocarditis cases. The incidence of tricuspid lesions in IVDU is approximately 50–65%, with a prevalence of about 2–5% per year [6]. With ongoing IVDU, IE reoccurs in about 28% of cases due to prior damage or replacement of the valve [6]. *Staphylococcus aureus* is the predominant causative organism in TVIE, just as in all types on of IE [4, 6]. The opioid epidemic over the last several years has seen an increase in patients with IVDU as subsequently an increase in TVE. Heroin abuse has more than doubled over the past decade along with TVE during the same period. A study by Wallen et al. showed a fivefold increase in surgical volume for tricuspid endocarditis from 2011 to 2017. In addition, the average age of patients seemed to decrease from 52.85 +/−19.6 years to 39.2 +/−12.9 over the same five-year period [7]. In addition, multiple other studies have reported an increase in tricuspid-related IE corresponding to an increase in IVDU during the same period [8–10].

#### *2.1.2 Treatment and prognosis*

As a whole, RSIE carries a good prognosis. TVIE clears in 70–85% of cases with antibiotic treatment alone. Non-operatively treated TVIE carries an in-hospital mortality of 7–11% [6]. Non operative treatment typically consists of 4–6 weeks of intravenous antibiotics. However, approximately 5–16% cases of RSIE will require surgical intervention [6]. Indications and timing for surgery are less clear

**145**

*Contemporary and Evolving Treatment of Tricuspid Endocarditis*

*S. aureus*, and vegetation greater than 20 mm [6].

*2.1.3 Current surgical options*

for RSIE than for left-sided infectious endocarditis (LSIE). According to the most recent AHA/ACC guidelines*,* surgery for native RSIE is indicated for patients with antibiotic failure, multi-drug-resistant organisms, tricuspid vegetations greater than 2 cm, embolic complications, or right-sided heart failure with poor response to diuretics [11, 12]. Most patients with infected prosthetic TV will require surgery, except in patients with unacceptable intra-operative mortality risk [6]. Surgery is less often performed for TV regurgitation due to IE, as it is more amendable to medical management and unlike aortic or mitral valve regurgitation, most patients can tolerate TV regurgitation up to a certain period [6]. Patients with isolated TVIE have an operative mortality between 0 and 15% and excellent survival. The postsurgical in-hospital mortality for TVIE is less than 10% and long term post-surgical mortality for TVIE is less than 15%, but increased in the presence of additional risk factors such as continued intravenous drug abuse, hemodialysis, valve replacement,

Over the years, various surgical options have been used in TVIE. Surgical options range from valve repair or replacement to the removal of the tricuspid valve leaflets and chordae tendinae without replacement (valvectomy). Valvectomy, essentially commits the patient to require surgical repair, but has been used with success to temporize a patient while fighting ongoing systemic infection [6]. According to a systematic review by Luc et al., the post-operative 30-day mortality, right heart failure, and recurrent endocarditis was the same with valvectomy compared to surgical valve replacement for endocarditis but with a slightly higher non-significant trend towards higher postoperative right heart failure and 30-day mortality [13]. Tricuspid reoperation rate, however, was higher in valvectomy (56%) versus valve replacement (14%) in addition to an increased likelihood of

Tricuspid valvectomy can be a feasible option in patients with active ongoing IVDU, normal pulmonary pressure, normal biventricular heart function, high degree of valvular destruction and high risk of reoperation, recidivism and recurrence for infection [13, 14]. Valvectomy with valve replacement as a staged procedure can allow patients to self-select in terms of their ability to maintain adequate follow-up, undergo detoxification and drug rehabilitation, optimize their social and financial situation, and demonstrate abstinence from IVDU prior to tricuspid valve replacement. However, valvectomy is largely falling out of favor due to the potential of severe right heart failure and the ventricularization of right atrial pressures [13, 15]. In patients with normal heart function pre valvectomy, severe right heart failure with symptoms of peripheral edema and ascites can occur within 6–9 months post valvectomy [6]. Therefore, patient with elevated pulmonary artery

The preferred surgical procedure is that of repair, particularly because it adheres

to the basic principles cited for the successful surgical treatment of infective endocarditis. These include aggressive and extensive debridement of vegetations; correction of defects that have developed; use of autologous tissue to avoid implantation of artificial material [13, 16]. Most centers will prioritize valve repair prior to

Both bioprosthetic valves and mechanical valves have been used for valve replacement in TVIE. The gold standard anticoagulation after mechanical valve

prolonged ventilation (40% vs. 26%) in the valvectomy group [13].

pressure are therefore not candidates for complete valvectomy [6].

valve replacement or valvectomy [13].

*2.1.4 Valve choice with replacement*

*DOI: http://dx.doi.org/10.5772/intechopen.95434*

#### *Contemporary and Evolving Treatment of Tricuspid Endocarditis DOI: http://dx.doi.org/10.5772/intechopen.95434*

for RSIE than for left-sided infectious endocarditis (LSIE). According to the most recent AHA/ACC guidelines*,* surgery for native RSIE is indicated for patients with antibiotic failure, multi-drug-resistant organisms, tricuspid vegetations greater than 2 cm, embolic complications, or right-sided heart failure with poor response to diuretics [11, 12]. Most patients with infected prosthetic TV will require surgery, except in patients with unacceptable intra-operative mortality risk [6]. Surgery is less often performed for TV regurgitation due to IE, as it is more amendable to medical management and unlike aortic or mitral valve regurgitation, most patients can tolerate TV regurgitation up to a certain period [6]. Patients with isolated TVIE have an operative mortality between 0 and 15% and excellent survival. The postsurgical in-hospital mortality for TVIE is less than 10% and long term post-surgical mortality for TVIE is less than 15%, but increased in the presence of additional risk factors such as continued intravenous drug abuse, hemodialysis, valve replacement, *S. aureus*, and vegetation greater than 20 mm [6].

#### *2.1.3 Current surgical options*

*Advanced Concepts in Endocarditis - 2021*

**2. Right sided infective endocarditis**

care-associated IE [5].

*2.1.1 Epidemiology*

**2.1 Tricuspid valve endocarditis**

*2.1.2 Treatment and prognosis*

and *Tropheryma whipplei* [5]. Endocarditis is characterized by lesions, known as vegetations. These vegetations follow endocardial injury where platelets and fibrin form a nidus which becomes secondarily infected by microorganisms circulating in the blood. (1) Endocarditis can involve both the right and left side of the heart and often can have differing causative organisms and etiologies. Left sided endocarditis can involve the aortic valve, mitral valve and in severe cases can involve the aortomitral curtain causing damage to the electrical structures of the heart. Right sided endocarditis typically involves the valvular structures on the right side of the heart most commonly the tricuspid valve and less often the pulmonary valve. In addition, the right sided endocarditis may also involve foreign bodies that are typically found

Right sided Infective Endocarditis (RSIE) accounts for about 10% of all IE cases [6]. Typically, these patients are younger with fewer medical comorbidities and less underlying valve disease as compared to patients with left-sided IE [6]. RSIE involves both tricuspid valve endocarditis (TVE) and cardiac implantable device endocarditis (CIDE). RSIE is most frequently seen with intravenous drug use (IVDU). Other predisposing risk factors include use of central venous catheters, cardiovascular implanted electronic devices, congenital heart disease, prosthetic heart valves, and end-stage renal disease on hemodialysis [5, 6]. Mortality rate of RSIE is typically 5–15% [6]. The risk factors and independent predictors of death are age, *Staphylococcus aureus* infection, heart failure, embolic events and health

Ninety percent of RSIE involves the tricuspid valve, of which infection resulting from intravenous drug use (IVDU) constitutes approximately 30–40% of all tricuspid valve endocarditis cases. The incidence of tricuspid lesions in IVDU is approximately 50–65%, with a prevalence of about 2–5% per year [6]. With ongoing IVDU, IE reoccurs in about 28% of cases due to prior damage or replacement of the valve [6]. *Staphylococcus aureus* is the predominant causative organism in TVIE, just as in all types on of IE [4, 6]. The opioid epidemic over the last several years has seen an increase in patients with IVDU as subsequently an increase in TVE. Heroin abuse has more than doubled over the past decade along with TVE during the same period. A study by Wallen et al. showed a fivefold increase in surgical volume for tricuspid endocarditis from 2011 to 2017. In addition, the average age of patients seemed to decrease from 52.85 +/−19.6 years to 39.2 +/−12.9 over the same five-year period [7]. In addition, multiple other studies have reported an increase in tricuspid-related IE

As a whole, RSIE carries a good prognosis. TVIE clears in 70–85% of cases with antibiotic treatment alone. Non-operatively treated TVIE carries an in-hospital mortality of 7–11% [6]. Non operative treatment typically consists of 4–6 weeks of intravenous antibiotics. However, approximately 5–16% cases of RSIE will require surgical intervention [6]. Indications and timing for surgery are less clear

corresponding to an increase in IVDU during the same period [8–10].

transversing the right atrium such as pacemaker leads, central lines.

**144**

Over the years, various surgical options have been used in TVIE. Surgical options range from valve repair or replacement to the removal of the tricuspid valve leaflets and chordae tendinae without replacement (valvectomy). Valvectomy, essentially commits the patient to require surgical repair, but has been used with success to temporize a patient while fighting ongoing systemic infection [6]. According to a systematic review by Luc et al., the post-operative 30-day mortality, right heart failure, and recurrent endocarditis was the same with valvectomy compared to surgical valve replacement for endocarditis but with a slightly higher non-significant trend towards higher postoperative right heart failure and 30-day mortality [13]. Tricuspid reoperation rate, however, was higher in valvectomy (56%) versus valve replacement (14%) in addition to an increased likelihood of prolonged ventilation (40% vs. 26%) in the valvectomy group [13].

Tricuspid valvectomy can be a feasible option in patients with active ongoing IVDU, normal pulmonary pressure, normal biventricular heart function, high degree of valvular destruction and high risk of reoperation, recidivism and recurrence for infection [13, 14]. Valvectomy with valve replacement as a staged procedure can allow patients to self-select in terms of their ability to maintain adequate follow-up, undergo detoxification and drug rehabilitation, optimize their social and financial situation, and demonstrate abstinence from IVDU prior to tricuspid valve replacement. However, valvectomy is largely falling out of favor due to the potential of severe right heart failure and the ventricularization of right atrial pressures [13, 15]. In patients with normal heart function pre valvectomy, severe right heart failure with symptoms of peripheral edema and ascites can occur within 6–9 months post valvectomy [6]. Therefore, patient with elevated pulmonary artery pressure are therefore not candidates for complete valvectomy [6].

The preferred surgical procedure is that of repair, particularly because it adheres to the basic principles cited for the successful surgical treatment of infective endocarditis. These include aggressive and extensive debridement of vegetations; correction of defects that have developed; use of autologous tissue to avoid implantation of artificial material [13, 16]. Most centers will prioritize valve repair prior to valve replacement or valvectomy [13].

#### *2.1.4 Valve choice with replacement*

Both bioprosthetic valves and mechanical valves have been used for valve replacement in TVIE. The gold standard anticoagulation after mechanical valve replacement is warfarin. Warfarin is can be difficult to manage as levels are dependent on patients' variable vitamin K intake and requires frequent monitoring. Furthermore, problems with compliance with monitoring and anticoagulation therapy is more frequently seen in patients with IVDU and this population is also the most common to present with recurrent right-sided endocarditis and require surgery for valve replacement. With bioprosthetic valve replacement, only first three months of anticoagulation after replacement are required to prevent thrombosis, although this practice itself can be variable [17, 18]. This time frame allows for reendothelialization to the suture zone [17]. Due to decreased duration of anticoagulation, bioprosthetic valves are associated with lower rates of bleeding complications [19].

Another advantage of bioprosthetic valve replacement compared to mechanical valve, is the thrombosis risk. Obstruction of the tricuspid mechanical prosthesis due to thrombosis is 20 times more frequent than left-sided prosthetic valve thrombosis [17]. This is likely due to low flow state of the right heart compared to the left. Lastly, Patients with bioprosthetic valve replacement are still candidates for pacemaker and ICD placement as compared to mechanical valves [6]. Similarly, embolic events are more common with mechanical valves [19]. Ergo, prosthetic valve replacement may be a better option from this perspective. Mechanical tricuspid valve replacement may be beneficial from the durability perspective as they last longer than bioprosthetic valves [6, 19]. Previously average failure time for tricuspid bioprosthetic valve was 7 years [19]. However, the durability of new bioprosthetic valves have improved over the years as recent data suggest no difference in long term data between bioprosthetic and mechanical valves at 15 years [20]. Additionally, mitral homografts have been used in the tricuspid space but with limited experience and long-term data [21].

#### *2.1.5 Percutaneous options for valve replacement*

Percutaneous tricuspid valve replacement (PTVR) creates unique challenges as compared to the left side. One, the tricuspid annulus is large is size compared to the mitral annulus and can be further increased with right ventricular dilation. For large valve replacement, large caliber sheaths and large bore venous access must be obtained [22]. Only jugular and femoral veins can accommodate such large bores of up to 45 French [22]. Trans-atrial approach has been used in the past; however, this requires surgical expertise. Two, tricuspid valves are more difficult to anchor percutaneously as there is limited calcification and the structure itself is dynamic (changes in diameter in systole and diastole). Three, PTVR carries an increased risk post-procedural conduction defects just as with surgical repair [6, 21]. Frequently with percutaneous replacement the tricuspid annulus becomes stretched. This can cause a complete atrio-ventricular (AV) block, requiring pacemaker placement, due to proximity of the AV node and the bundle of His to the tricuspid valve. Similarly, proximity of the tricuspid valve to the right coronary artery, coronary sinus, vena cava create additional challenges with percutaneous placement and valve design [22]. Furthermore, patients with pacemaker or ICD devices are not great candidates for percutaneous tricuspid valve replacement as placement of a valve may dislodge leads. Lastly, there is very limited data on the percutaneously placed tricuspid valve replacement durability and more studies are necessary. Unlike, for surgical tricuspid valve replacement there are no guidelines regarding timing of percutaneous valve aortic valve replacement after infective endocarditis. Without surgical debridement or percutaneous debulking and with antibiotics use alone, there is a high theoretical reinfection risk of the new tricuspid valve placed using a percutaneous approach after endocarditis.

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*Contemporary and Evolving Treatment of Tricuspid Endocarditis*

Cardiac implantable device endocarditis (CIDE) involves cardiovascular implantable electronic devices (CIED) which include permanent pacemakers (PPM), implantable cardiac defibrillators (ICD), and cardiac resynchronization systems (CRT). CIDE is diagnosed based on the presence of the following four

• A positive culture for typical causative agents from the pocket of the device or

• Echocardiographic findings of vegetation on the tricuspid valve or at the end

Specifically, for CIDE diagnosis, the Duke criteria should be used. Patient presentation can be variable and can involve all or just a few symptom including fevers, rigors, anorexia, fatigue, local tissue inflammation. In addition, there may be possible purulent discharge, device exposure, focal pain that may help localize the primary site of infection. Other symptoms could be neurologic or cardiac consistent

Intracardiac device infections constitute approximately 10% of all endocarditis cases [24]. CIEDs have been implanted in patient as early as 1960s, but over the last two decades had significant increase in incidence. According to American Heart Association update, between 1997 and 2004, PPM placement increased by 19% and ICD placement increased by 60% [25]. Other studies quote an even higher increase of 30% for PPM and over 500% for ICDs [26]. In the United States greater than 500,000 PPMs and ICDs are implanted per year with over 4 million implanted between 1993 and 2008 [27]. Notably, more patients who are elderly and those with many comorbidities have been receiving these devices [25]. In developed countries

Over the years, changing the implantation site of ICD from abdomen (associated with 3.2% infection rate) to pectoral site (associated with 0.5% infection rate) initially decreased the incidence of device related infections [25]. Despite the innovation in PPM and ICD technology together with better surgical technique, the rate of infections associated with cardiac devices has increased by 124–210% [25, 26]. About 1.8–31.1 cases of CIED infection per 1000 device years has been reported for PPM and ICD devices and overall higher rates of infection with ICDs and CRTs [27]. This change is likely due to increased rate of CIED implantation in people over the age of 65 and presences of major comorbidities such as renal failure, respiratory failure, heart failure and diabetes [26]. CIED infections are associated with up to 18% of morbidity and mortality and increase by 47% per decade hospital charges [26]. Early infection typically arises from device implantation [27]. With first time implantation the rate of CIED related infection is 0.5–1% and 1–5% with device replacement or upgrade [27]. CIED related infection can involve the bloodstream, the generator pocket, the leads, or endocardial structures [26, 27]. Late infection typically arises from patient poor health or other clinically significant processes.

20–35% of CIEDs were placed in patients older than 80 years of age [25].

with embolic stroke, or symptoms of volume overload [23].

*DOI: http://dx.doi.org/10.5772/intechopen.95434*

• Presence of a cardiac device;

• No other source of infection;

of the electrical lead [23].

its leads; and

*2.2.1 Epidemiology*

criteria:

**2.2 Cardiac implantable device endocarditis**
