More than Garden Variety: Massive Vegetations from Infective Endocarditis

Infective endocarditis classically involves non-sterile vegetations on valvular surfaces in the heart. Feared complications include embolization and acute heart failure. Surgical intervention achieves source control and alleviates valvular regurgitation in complicated cases. Vegetations >1 cm are often intervened upon, making massive vegetations uncommon in modern practice. We report the case of a 39-year-old female with history of intravenous drug abuse who presented with a serpiginous vegetation on the native tricuspid valve and methicillin-resistant Staphylococcus aureus bacteremia. The vegetation grew to 5.6 cm by hospital day two, and she successfully underwent a tricuspid valvectomy. Six weeks of intravenous vancomycin therapy were completed without adverse events. To better characterize other dramatic presentations of infective endocarditis, we performed a systematic literature review and summarized all case reports involving ≥4 cm vegetations.

We report the case of a 39-year-old female with history of intravenous drug abuse (IVDA) who presented with a serpiginous vegetation on the native tricuspid valve and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. The vegetation grew to 5.6 cm, and she underwent a tricuspid valvectomy. Six weeks of intravenous (IV) vancomycin were completed without adverse events. We performed a systematic literature review and summarized all case reports involving ≥4 cm vegetations.

Case Presentation
A 39-year-old female with a history of IVDA and untreated hepatitis C presented to the emergency department with a two-week history of malaise, arthralgias, and myalgias accompanied by a non-productive cough. In the preceding years, she had multiple admissions for MRSA soft tissue abscesses, MRSA septic arthritis, MRSA pneumonia, and one episode of MRSA bacteremia. In the emergency department, she was febrile (40 • C, rectal) and tachycardic. No peripheral stigmata of endocarditis were noted on physical exam. Blood cultures were obtained before empiric IV vancomycin and piperacillin-tazobactam were started.
On admission, laboratory investigations were notable for hyponatremia (126 mmol/L; ref. range 136-144 mmol/L) and an absence of leukocytosis (9900/µL; ref. range 4000-10,000/µL). Transthoracic echocardiography revealed tricuspid regurgitation and a large, serpiginous vegetation on the septal leaflet of the tricuspid valve. Additionally, a chest radiograph demonstrated patchy opacities in multiple lobes, which were concerning for septic emboli.
Blood cultures grew MRSA the following day, and antimicrobial therapy was narrowed to IV vancomycin. A transesophageal echocardiogram showed progression to severe tricuspid regurgitation with all three leaflets affected by destructive vegetations. The vegetation on the septal leaflet had grown to 5.6 cm and extended into the right atrium ( Figure 1). She was transferred to our institution's primary hospital for surgical management.
Pathogens 2020, 9, x FOR PEER REVIEW 2 of 8 endocarditis were noted on physical exam. Blood cultures were obtained before empiric IV vancomycin and piperacillin-tazobactam were started. On admission, laboratory investigations were notable for hyponatremia (126 mmol/L; ref. range 136-144 mmol/L) and an absence of leukocytosis (9900/μL; ref. range 4000-10,000/μL). Transthoracic echocardiography revealed tricuspid regurgitation and a large, serpiginous vegetation on the septal leaflet of the tricuspid valve. Additionally, a chest radiograph demonstrated patchy opacities in multiple lobes, which were concerning for septic emboli.
Blood cultures grew MRSA the following day, and antimicrobial therapy was narrowed to IV vancomycin. A transesophageal echocardiogram showed progression to severe tricuspid regurgitation with all three leaflets affected by destructive vegetations. The vegetation on the septal leaflet had grown to 5.6 cm and extended into the right atrium ( Figure 1). She was transferred to our institution's primary hospital for surgical management. On hospital day three, she underwent tricuspid valvectomy. A median sternotomy was performed. Ascending aorta and bicaval cannulation were carried out for cardiopulmonary bypass. The right atrium was opened through an oblique atriotomy. Extensive destruction of the tricuspid valve was noted intraoperatively, and all leaflets were excised and debrided down to the tips of the papillary muscles. The annulus was also debrided. Cardiopulmonary bypass was weaned without complication. Stainless-steel wires were used to close the sternum, with absorbable sutures for skin and subcutaneous tissues. Debrided tissue was submitted for culture and subsequently grew MRSA.
Postoperatively, she required vasopressor support and remained intubated. Her leukocytosis (19,000/μL) peaked on hospital day four, so IV piperacillin-tazobactam was restarted. Blood cultures taken the same day returned positive for MRSA. By hospital day six, she was extubated and weaned from vasopressor support. Antimicrobial therapy was again narrowed to IV vancomycin. Blood cultures taken on hospital day seven returned negative, and a treatment plan to receive six-weeks of IV vancomycin starting from this date was made. Imaging studies in the following days demonstrated cavitary lesions in both lungs ( Figure 2) and possible C4-C5 vertebral discitis and On hospital day three, she underwent tricuspid valvectomy. A median sternotomy was performed. Ascending aorta and bicaval cannulation were carried out for cardiopulmonary bypass. The right atrium was opened through an oblique atriotomy. Extensive destruction of the tricuspid valve was noted intraoperatively, and all leaflets were excised and debrided down to the tips of the papillary muscles. The annulus was also debrided. Cardiopulmonary bypass was weaned without complication. Stainless-steel wires were used to close the sternum, with absorbable sutures for skin and subcutaneous tissues. Debrided tissue was submitted for culture and subsequently grew MRSA.
Postoperatively, she required vasopressor support and remained intubated. Her leukocytosis (19,000/µL) peaked on hospital day four, so IV piperacillin-tazobactam was restarted. Blood cultures taken the same day returned positive for MRSA. By hospital day six, she was extubated and weaned from vasopressor support. Antimicrobial therapy was again narrowed to IV vancomycin. Blood cultures taken on hospital day seven returned negative, and a treatment plan to receive six-weeks of IV vancomycin starting from this date was made. Imaging studies in the following days demonstrated cavitary lesions in both lungs ( Figure 2) and possible C4-C5 vertebral discitis and osteomyelitis; however, no further surgical interventions were required. She was discharged on hospital day 18. osteomyelitis; however, no further surgical interventions were required. She was discharged on hospital day 18. As an outpatient, she was seen 28 days after discharge and had been tolerating vancomycin. She reported resolution of her constitutional symptoms, yet she continued to experience diffuse arthralgias and joint swelling. Her six-week course of vancomycin was completed five days later, and she went on to be diagnosed with seronegative rheumatoid arthritis in the coming months.
The review of medical records was conducted in accordance with the Declaration of Helsinki. The protocol was approved by the Institutional Review Board of Yale University (2000028148), and need for informed consent was waived.

Discussion
Our case concerned a 39-year-old female with a history of IVDA who presented with infective endocarditis and MRSA bacteremia. A 5.6 cm serpiginous vegetation was visualized on her tricuspid valve, and she successfully underwent tricuspid valvectomy followed by vancomycin monotherapy for six weeks. Large vegetations are associated with higher morbidity and mortality [2][3][4][5] Table 1 summarizes all reported cases and our case. The mean age was 46 years, and 52% were male. The As an outpatient, she was seen 28 days after discharge and had been tolerating vancomycin. She reported resolution of her constitutional symptoms, yet she continued to experience diffuse arthralgias and joint swelling. Her six-week course of vancomycin was completed five days later, and she went on to be diagnosed with seronegative rheumatoid arthritis in the coming months.
The review of medical records was conducted in accordance with the Declaration of Helsinki. The protocol was approved by the Institutional Review Board of Yale University (2000028148), and need for informed consent was waived.

Discussion
Our case concerned a 39-year-old female with a history of IVDA who presented with infective endocarditis and MRSA bacteremia. A 5.6 cm serpiginous vegetation was visualized on her tricuspid valve, and she successfully underwent tricuspid valvectomy followed by vancomycin monotherapy for six weeks. Large vegetations are associated with higher morbidity and mortality [2][3][4][5] Table 1 summarizes all reported cases and our case. The mean age was 46 years, and 52% were male. The mean vegetation length was 5.5 cm (range 4-10 cm), and 39% of cases involved native tricuspid valves. Gram-positive bacteria accounted for most cases (14 of 23), and fungal pathogens were identified in 5 of 23 cases. Surgical intervention occurred in 16 of 23 cases, with percutaneous catheter-based intervention used in one case [6]. Length of targeted antimicrobial therapy ranged from <1-10 weeks. Overall mortality was 43% (9 of 21).

Conclusions
Our review of four decades of literature demonstrates that ≥4 cm vegetations are exceptional. Overall, advancements in echocardiography and surgical technique have made the diagnosis and management of infective endocarditis more standardized [1]. Nonetheless, massive vegetations are possible and benefit from a multidisciplinary approach to management.