A novel approach, AngioVac use in right-sided infective endocarditis: a scoping review

Background Infective endocarditis is an infection of microbial origin affecting the endocardial layer of the heart, mostly impacting the heart valves. Right-sided infective endocarditis mainly affects the tricuspid valve. In some cases where surgical management is indicated the patients might not be good candidates for surgery. The AngioVac drainage cannula (AngioDynamics, Latham, NY, USA) is a novel device used in debulking and suction of intravascular material. It has been reported in the literature as a novel treatment for patients with right-sided tricuspid valve endocarditis vegetations, where their size is reduced and the efficacy of antibiotics in clearing the bloodstream infection is enhanced. Methods and results We conducted a thorough literature review to assess the uses of the AngioVac drainage cannula in the management of right-sided infective endocarditis vegetations and lesions. We collected all reported cases where the system was used for the management of right-sided infective endocarditis and performed an encompassing review of the literature. In the review, we found 65 cases reported using the AngioVac drainage cannula for the removal of right-sided infective endocarditis vegetations. Majority of the cases were successful with no complications (87.6%); 7 (10.7%) cases were successful but there were complications: 2 reported mortalities, 1 patient had worsening TR during follow-up, 3 had recurrence of the vegetation, and 1 patient remained bacteremic. There was only 1 reported failure. Four (6.1%) patients required postprocedural valvular surgery with 3 repairs and a single valve replacement. Conclusions The AngioVac system is a possible bailout option for surgeons managing patients with right-sided infective endocarditis vegetations who are not ideal candidates for surgery. With increased reports on its use, it could be effective at reducing the microbiological burden with minimal complications


Background
Infective endocarditis (IE) is an infection of microbial origin affecting the endocardial layer of the heart, mostly impacting the heart valves.Right-sided infective endocarditis (RSIE) is much less common than left-sided endocarditis and mainly affects the tricuspid valve.The underlying causes of infection mainly arise from congenital or acquired valve disease, indwelling catheters such as a tunneled dialysis catheter or central lines, hematological spread of bacterial oral flora from dental procedures, intravenous drug abuse (IVDA), prosthetic valves, and implanted cardiac devices [1,2].Approximately 90% of the organisms causing IE are Staphylococcus species, Streptococcus species, and Enterococcus species, with Staphylococcus aureus being the most common microorganism associated with IE [3].
IE leads to heart valve vegetations that break from the valve causing emboli that affect multiple organs, leading to a plethora of symptoms including fever, shortness of breath, chest pain, lower limb edema, painful fingertip nodules (Osler nodes), hand and feet painless lesions (Janeway lesions), retinal hemorrhages (Roth spots), and flu-like symptoms.Severe IE can also lead to lifethreatening complications such as acute heart failure, pulmonary septic embolism, and stroke, if not treated effectively [3].
The treatment of infective endocarditis stands on two pillars: (1) the eradication of the organisms by appropriate antibiotic coverage, (2) surgical removal of the vegetation, if indicated, to decrease the microbiological burden.In some cases where surgical management is indicated, some patients have an increased risk for morbidity and mortality if they undergo surgery, due to multiple causes, such as frailty status that may not tolerate surgery or a critically ill patient.The AngioVac (AngioDynamics, Latham, NY, USA) is a minimally invasive percutaneous aspiration system that can be used to debulk tricuspid valve vegetations in patients with a high operative risk.The concept of debulking tricuspid valve vegetations aims to reduce bacterial load in order to allow antimicrobial therapy to cure the infection or to stabilize the patient as a bridge to surgery [3].
The primary objectives of this study were (1) to identify the outcomes of the use of the AngioVac system in the setting of RSIE and (2) to review the relevant literature on this topic.

Methods
Data sources and search strategy F.M.S and A.S.S comprehensively searched PubMed, Embase, Cochrane Library, and Web of Science up to January 2024.The following keywords were used: Angio-Vac, Percutaneous debulking, Percutaneous suction, Percutaneous vegetectomy, and Endocarditis.The search process involved no limitations.We also screened the selected reports' reference lists for other relevant reports.The detailed search strategy and results can be found in supplementary Table S1.

Eligibility criteria
We included case reports and case series articles that reported the use of the AngioVac cannula in the setting of RSIE.Our inclusion criteria were limited to articles published in peer-reviewed international journals.We excluded articles that did not align with our predefined eligibility criteria.

Study selection
All identified studies were imported into Covidence from online databases, and duplicates were automatically removed.Two authors (F.M.S and A.S.S) independently screened the title and abstract with any conflicts arising resolved by the authors (A.H.B and M.A.F).Fulltext screening was performed by the authors F.M.S and A.S.S, and the conflicts were settled by the authors A.H.B and M.A.F.The study selection process is illustrated in a PRISMA flow chart (Fig. 1).

Data extraction
Two authors (F.M.S and A.S.S) independently extracted the following data: age, sex, risk factor for developing infective endocarditis, preprocedural vegetation size, vegetation location, preprocedural tricuspid valve regurgitation severity, isolated organism, contraindication for surgery, cannulation sites, postprocedural vegetation size, postprocedural tricuspid valve regurgitation severity, patient outcome, and the need for surgery.Any conflict was handled by the authors A.H.B and M.A.F.

Search results and study selection
A total of 1722 records were identified after searching electronic databases.After eliminating 151 duplicated articles, 1571 studies were eligible for title and abstract screening.Nine hundred eighty-nine studies were excluded due to their lack of relevance to the research objectives.Five hundred eighty-two articles proceeded to full-text screening with 534 being excluded.In this review, a total of 48 publications were included with a total of 65 patients reported to undergo the usage of AngioVac in the setting of RSIE.Detailed patient characteristics and data are included in Table 1.

Patient demographics
The median age of the patient was 40 years old (IQR,  with the majority being males with 36 (55.3%) patients, and of note, 3 of the female patients were pregnant (Table 2).

Risk factors for developing RSIE
The most common risk factor was the abuse of intravenous drugs reported in 25 (38.4%)patients, followed by cardiac implantable electronic devices (CIED) in 22 (33.7%)patients, 5 (7.6%) patients were reported to have a bioprosthetic valve.Also, another 5 (7.6%) patients had tunneled dialysis catheters.Only 2 (3.07%) patients had a distant infection with both of them having osteomyelitis.Two (3.07%) patients had a combination of risk factors (Table 2).

Indications for AngioVac system
The main cause was lack of surgical candidacy in 23 (35.3%) patients who had multiple comorbid conditions with 8 (12.3%) of them having severely depressed cardiac function with cardiomyopathy.The other most common cause was hemodynamic instability in 23 (35.3%) patients as well.Three (4.6%) patients had prior cardiac surgery.Also, another 3 (4.6%)patients had extensive septic pulmonary emboli.Recurrent intravenous drug abuse was a contraindication for surgery in 2 (3.07%) patients.One (1.5%) patient had a pulmonary artery aneurysm, and 1 (1.5%) patient was reported to refuse offered surgery (Table 2).

Location of the vegetation
The most common site was the tricuspid valve in 36 (55.3%) patients, followed by the vegetations forming on a lead of a CIED in 12 (18.4%)patients; 5 (7.6%) cases were reported to be on a bioprosthetic valve, 2 (3.07%) cases in the right atrium.The right ventricle, superior vena cava, chiari network, pulmonary valve, and tricuspid valve annuloplasty were each reported only once (1.5%).Six (9.2%) patients had multiple vegetations (Table 3).

Preprocedural echocardiographic findings
The median size of the vegetations reported was 24 mm (IQR, .Preprocedural tricuspid regurgitation (TR) was reported to be mild in 8 (12.3%) cases, moderate in     3).

Postprocedural echocardiographic findings
Sixteen (24.6%) cases reported complete reduction (100%) of the vegetation, 22 (33.8%) reported satisfactory reduction (> 70%), and only 3 (4.6%)cases reported unsatisfactory reduction (< 70%).It is to be noted that 3 (4.6%)cases were reported by the authors to have satisfactory reduction but no postprocedural size or percentage of reduction being reported.As for the postprocedural TR, 9 (13.8%)cases reported worsening, 3 (4.6%)cases reported improvement, and 4 (6.1%)cases reported the same degree of TR with 3 of 4 cases were reported as severe TR preprocedural and remained at the same degree.Unfortunately, the majority of the studies did not report the degree of postprocedural TR (Table 4).

Postprocedural outcomes
Majority of the cases were successful with no complications (87.6%); 7 (10.7%)cases were successful but there were complications: 2 reported mortalities, 1 patient had worsening TR during follow-up, 3 had recurrence of the vegetation, and 1 patient remained bacteremic.There  was only 1 reported failure.Four (6.1%) patients required postprocedural valvular surgery with 3 repairs and a single valve replacement (Table 4).

Discussion
RSIE accounts for 10% of all IE cases and continues to rise, with an aging multi-morbid population.Nearly 90% of all RSIE occurs in patients who use injectable drugs, 9% in patients with CIED or intravascular devices, and 1% in those with congenital heart disease (CHD) [4,5].Disease development in individuals who abuse intravenous drugs is caused by direct endothelial damage as well as the introduction of organisms through injection sites from the skin or as a contaminant in the drug.For individuals with intravascular or cardiac implantable electronic devices, contamination is frequently initiated during handling or implantation.Most RSIE (60-90%) is by infection with Staphylococcus aureus, thereafter streptococcal, gram-negative, or HACEK bacteria.While RSIE involving intravascular catheters or prosthetic valves is caused by MSSA, MRSA and fungal organisms are the cause in the presence of immunosuppression, cardiac implanted devices, and intravenous drug abuse [6].
The diagnosis of IE can be determined using the modified Duke criteria.This includes a list of major and minor criteria, that, when fulfilled, most likely suggest IE.The major modified Duke criteria are blood culture positive for IE causative organisms and evidence of endocardial involvement.The minor criteria include a predisposing heart condition, intravenous venous drug use, fever of 38 °C, vascular phenomena, including major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages and Janeway lesions, immunological phenomena such as Osler nodes, glomerulonephritis, Roth spots, rheumatoid factor, and microbiological evidence.The criteria are fulfilled when one major and one minor or three minor criteria are met [6].
The mainstay of treatment for RSIE is intravenous antibiotic therapy of the underlying infection and the removal of the underlying source of infection by either the removal of causative intravascular devices or surgical removal of the infected prosthetic valve or valvular vegetation [4][5][6].
As patients can rapidly decompensate, necessitating surgical intervention, ideally, they should be managed by a multidisciplinary team consisting of microbiologists, valve disease specialists, and cardiac surgeons.
The recent European guidelines by the European Society of Cardiology indicate surgery if the patient has the following: (1) persistent fungi or bacteremia for more than 7 days, despite adequate antibiotic therapy, (2) persistent tricuspid valve vegetations, greater than 20 mm in size, causing recurrent pulmonary embolism with or without right-sided heart failure, (3) right-sided heart failure caused by severe TR, not responsive to diuretic therapy, (4) if percutaneous removal of a CIED was incomplete, or not possible, or associated with severely destroyed tricuspid valve, and (5) if the CIED has large vegetations greater than 20 mm in size [7].
Recently, the American Heart Association guidelines stated that surgery is indicated for certain complications: (1) resistant infections caused by fungi or drug-resistant bacteria, (2) tricuspid valve vegetations more than 20 mm in size, (3) right-sided heart failure due to severe TR, without response to diuretic therapy, (4) recurrent pulmonary embolism despite appropriate antibiotic therapy and coverage.Also, valvular repair is preferred rather than replacement, when feasible, with an individualized prosthesis for every patient if valve replacement was performed, and avoiding surgery is recommended, when possible, in patients with a history of IVDA [8].
In cases where surgery is recommended, operative risk assessment is important to decide whether the risk-benefit analysis supports surgery being performed.
In recent years, several case reports and case series have introduced a novel, minimally invasive, technique using a percutaneous aspiration system to debulk tricuspid valve vegetations in patients with a high operative risk.This concept of debulking tricuspid valve vegetations aims to reduce bacterial load to allow antimicrobial therapy to cure the infection or to stabilize the patient as a bridge to surgery .This device is the AngioVAC system.The United States Food and Drug Administration (FDA) approved the AngioVac system for the removal of unwanted intravascular materials (thrombi and emboli) in 2014.Currently, the device is not approved to be used in the setting of RSIE vegetation removal, but recently, the device received the FDA breakthrough device designation to expand its use in RSIE.This designation will accelerate assessments and review processes to allow its approval in the near future [58].
The device comprises a venous drainage cannula and a reinfusion (venous return) cannula, which are connected to an extracorporeal circuit and a commercially available pump head and bubble trap.The venous drainage component is a 22-Fr cannula with a funnel-shaped distal tip that can be advanced through a 26-Fr sheath over a guidewire, percutaneously, into the venous system.When the pump is started, a suction force is created that facilitates aspiration of blood and thrombotic materials into the tip of the AngioVac cannula, circulating the blood through a filter.After filtration, the drained blood is returned to the patient via a second percutaneously placed reinfusion venous cannula, through the internal jugular or femoral vein.The recirculation of venous blood minimizes intra-procedural blood loss and the requirement for blood transfusion (Fig. 2) [59].
The venovenous extracorporeal circuit step used in our institute for the percutaneous aspiration consists of the 22 F AngioVac (Gen 3) 20° suction cannula for venous drainage, a CAPIOX ® BT15 bubble trap (Terumo Cardiovascular, Ann Arbor, MI, USA) as a filter for aspirated thrombotic material, an Affinity ™ centrifugal pump (Medtronic, Minneapolis, Minnesota, USA), and a 18-F Bio-Medicus ™ NextGen Femoral cannula (Medtronic, Minneapolis, Minnesota, USA) for venous return.During the procedure, heparin is used for anticoagulation with a target-activated clotting time of 250 to 300 s.The setup used is shown in Fig. 3.
As a first step, we percutaneously cannulate the left common femoral vein.After systemic heparin administration, an 18-F Bio-Medicus ™ NextGen Femoral cannula is introduced into the left femoral vein for venous return using Seldinger's technique and advanced until it reached the left iliac vein.The right common femoral vein was accessed by the same method.As a final step, prior to initiation of the extracorporeal circuit, the 22-F AngioVac (Gen 3) 20° angled tip cannula is introduced via the sheath.Under continuous fluoroscopy and transesophageal echocardiography guidance, the cannula is advanced from the right common femoral vein to the right iliac vein, to the inferior vena cava, to the right atrium, and both the return cannula, and the AngioVac suction cannula were connected to the extracorporeal circuit.
There are a limited number of case reports describing the use of the AngioVac device in the management of RSIE vegetations .
In a single-center study performed by George et al., 33 patients were analyzed (72.7% injection drug use, 3% a bioprosthetic valve, and 6.1% pacemaker or defibrillator device present).The patients all had large tricuspid valve vegetations (mean 2.1 ± 0.7 cm), 18% had severe preprocedural TR, and they underwent the vacuumassisted procedure for reduction of vegetation size and burden by the AngioVac device.It was reported that there was a 61% reduction in vegetation size with the use of the AngioVac system, with only three patients requiring tricuspid valve surgery due to worsening of their TR.There were no patient deaths from the procedure, with a hospital survivability of 90.0% [60].
Although the AngioVac system can be an excellent bailout option for patients with undesired surgical outcomes, there are complications.One of the most noticeable complications during our review was worsening of the TR, especially when the AngioVac was used on TV vegetations.This mainly occurs due to the high suction pressures on the tip of the cannula.To mitigate this compilation, proper visualization of the cannula should be of the utmost importance using continuous intra-procedural TEE to avoid damage to the TV and its structures.In our practice, we use a modified midesophageal 4-chamber view with an emphasis on the right-sided cardiac chambers and the use of continuous Doppler monitoring to assess the degree of the TR during the suction part of the procedure.
In a study performed by Worku et al., 56 patients underwent AngioVac procedures, and the success rate for removing thrombus in the right side of the heart was 82%.This same study reported a 12% complication rate that included hematoma and retroperitoneal hemorrhage.Another possible complication of an AngioVac procedure for vegetation removal on the tricuspid valve is worsening of tricuspid valve insufficiency, given the suctioning properties of the device [60].
In a review study of the Registry of AngioVac Procedures in Detail (RAPID) registry data performed by Moriarty et al., an analysis was conducted on adult patients who underwent AngioVAC removal of right heart thrombus.They reported that among the 47 patients, 42 (89.4%) of the thrombi were in the right atrium only, three (6.4%) were in the right ventricle, and two (4.3%) were in the right atrium and the right ventricle.Four (8.5%) patients had concomitant caval thrombi, three (6.4%) had catheter-related thrombi formation, and one patient had both caval-and catheter-related thrombi in combination with the right heart thrombi.With excellent outcomes stating that 70 to 100% removal of thrombus was achieved in 28 (59.6%)patients.One patient had hematoma at the site of the reinfusion catheter, and another patient developed pericardial effusion due to caval rupture that required drain insertion, and was discharged 2 days after the procedure.There was pulmonary embolization in three patients who were treated by anticoagulation with no requirement for an interventional procedure or mechanical support.There was one death, not related to the AngioVac, which occurred in a 43-yearold female who underwent a heart and liver transplant and subsequently developed a right ventricular thrombus and stroke, with her family electing to withdraw care [61].
A further analysis of the RAPID registry showed that the majority of the procedures were performed by either an interventional cardiologist or radiologist.So currently, cardiac surgeons are not the primary operators in most AngioVac cases.Even though our review showed that there was a lack of intra-procedural complications, this does not mean that unexpected adverse events cannot occur.So, even if a cardiac surgeon is not the main operator of the device, they should be present during such procedures to provide their unique skill set in the setting of an emergency.A multidisciplinary team approach is critical to provide the most optimum safety and outcomes.
Al Badri et al. described the percutaneous removal of right heart thrombus using vacuum aspiration in seven patients undergoing right atrial thrombectomy.Two of the patients in the series were diagnosed with submassive pulmonary embolism.The procedure was successful for six (85.7%) patients, and treatment was ultimately successful for the remaining patients who developed cardiogenic shock requiring brief extracorporeal membrane oxygenation.The authors reported no device or procedure-related complications.Additionally, no patients experienced a postprocedural decrease in hematocrit or required a transfusion.Their conclusion was that patients with right-sided intracardiac thrombus, who were hemodynamically stable, but not candidates for surgery, would benefit from vacuum thrombectomy [62].
Donaldson et al. reported on 15 procedures performed with the use of the AngioVac system.Eleven (73.3%) were removed from the right atrium, and the other four were removed from the right ventricle.Complete removal of the mass was achieved in 11 (73.3%)patients.Eleven patients had a decrease in hematocrit, with six (54.5%) requiring transfusion, and they did not report the development of vascular complications [63].
In a review of the Manufacturer and User Facility Device Experience (MAUDE) database, which contains reports submitted to the FDA by mandatory reporters: manufacturers, importers, and device user facilities and voluntary reporters: healthcare professionals, patients, and consumers, they assessed 93 reported failures of the AngioVac device, with the most common points of failure being physical damage in 13 reports (14.0%),occlusion of the suction cannula in five reports (5.4%), and development of air bubbles in two reports (2.2%).Physical damages to the cannula were the following: (1) breaks in two reports, (2) deflation and inflation issues in three reports, (3) entrapment of the device in two reports, failure to advance in three reports, and (4) inadequate device training in three reports.Reported complications were the following: (1) Thirty-four (36.6%) reports of pulmonary embolism, (2) 16 (17.2%)perforation, (3) four (4.3%) reports of arrhythmia, (4) three (3.2%)reports of stroke, and ( 5) one (1.1%)report of hematoma [64].
The results of our review show promising outcomes of the AngioVac cannula in the setting of RSIE, but it mainly looks at individual case reports and series.Further larger studies on the topic should be done looking at outcomes in a broader manner including but not limited to (1) its effects on TR postprocedural and during long-term follow-up, (2) comparing local versus general anesthesia on postprocedural outcomes and pain management, (3) effects of prolonged extracorporeal circulation on patient's hemoglobin level and need for transfusion, (4) comparing its outcomes in different patient profiles including patients with IVDU, (5) comparing it to surgery, and (6) prolonged long-term outcomes.

Limitations
There are some limitations to this study that should be acknowledged.Firstly, our sample size of 65 patients is small which is expected due to the novelty of the device.Secondly, some case reports were lackluster in reporting all of the postprocedural outcomes, especially the degree of postprocedural TR, hematological complication, and hospital length of stay.Thirdly, there was a lack of longterm follow-up in the reports.Fourthly, due to the lack of literature on the topic with the majority of the new article on it being case reports by centers using the device for the first time and lack of new retrospective studies, we decided that to limit our review to case reports and series to provide insight on how new facilities manage patients using this novel device and their outcomes.

Conclusions
The AngioVac system is a possible bailout option for patients with right-sided infective endocarditis vegetations who are not ideal candidates for surgery.Increased reports on its use have shown that it could be effective in the reduction of microbiological burden with minimal complications.However, more studies should be performed to determine the long-term effects and complications, with comparisons to surgical management in patients who are candidates for surgery and are well-suited for the use of the AngioVac system.

Fig. 2
Fig. 2 AngioVac guidance using intra-procedural imaging.A Introduction and deployment of the AngioVac cannula to the right atrium (yellow arrowhead indicating transesophageal echocardiography (TEE) probe, red arrowhead indicating the funnel tip of the AngioVac cannula.B Angulation of the AngioVac cannula to face the tricuspid valve (yellow arrowhead indicating transesophageal echocardiography (TEE) probe, red arrowhead indicating the funnel tip of the AngioVac cannula).C TEE-midesophageal 4 chamber view: revealing a 34 × 35 mm vegetation in the right atrium indicated by the red arrowhead.D TEE -midesophageal 4 chamber view: showing the engagement of the AngioVac cannula to the right atrial vegetation.E Transthoracic echocardiography 4 chamber view at 3 months follow-up revealing complete removal of the vegetation (see supplementary video 1))

Fig. 3
Fig. 3 AngioVac setup (showing our institute setup): A venovenous extracorporeal circuit consists of the 22-F AngioVac (Gen 3) 20° suction cannula (AngioDynamics, Latham, NY, USA) for venous drainage, a CAPIOX ® BT15 bubble trap (Terumo Cardiovascular, Ann Arbor, MI, USA) as a filter for aspirated thrombotic material, an Affinity ™ centrifugal pump (Medtronic, Minneapolis, Minnesota, USA), and a 18-F Bio-Medicus ™ NextGen Femoral cannula (Medtronic, Minneapolis, Minnesota, USA) for venous return.B The AngioVac cannula.C The cannulation Strategy a BI-femoral approach with the suction cannula placed in the right common femoral vein with the reperfusion cannula placed in the left common femoral vein

Table 1 (continued) Author, year Type of publication Age/Sex Risk factor Organism Pre-AngioVac vegetation size Pre-AngioVac Tricuspid regurgitation Location Contraindication to surgery Post-AngioVac vegetation size Post- AngioVac Tricuspid regurgitation AngioVac Access sites Need for operation for tricuspid valve Outcome of AngioVac
Reported cases of right-sided infective endocarditis treated by the AngioVac system