Retrospective Cohort Study Open Access
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. Jun 26, 2024; 16(6): 318-328
Published online Jun 26, 2024. doi: 10.4330/wjc.v16.i6.318
Echocardiographic predictors and associated outcomes of multiple vegetations in infective endocarditis: A pilot study
Ajay Kumar Mishra, Pradnya B Bhattad, Anil Jha, Nitish Sharma, Division of Cardiology, Saint Vincent Hospital, Worcester, MA 01608, United States
Kannu Bansal, Anu Anna George, Jennifer Sargent, Department of Internal Medicine, Saint Vincent Hospital, Worcester, MA 01608, United States
Ibragim Al-Seykal, Department of Medicine, Division of Cardiology, Saint Vincent Hospital, Worcester, MA 01608, United States
Mark J Kranis, Division of Cardiovascular Medicine, Saint Vincent Hospital, Worcester, MA 01608, United States
ORCID number: Ajay Kumar Mishra (0000-0003-4862-5053); Kannu Bansal (0000-0002-2978-6110); Ibragim Al-Seykal (0000-0001-5527-068X); Pradnya B Bhattad (0000-0003-3691-486X); Jennifer Sargent (0000-0003-0578-8944).
Author contributions: Mishra AK and Jha A planned and formulated the study; Al-Seykal I, Bhattad PB, and George AA collected and analyzed the data; Mishra AK, Bansal K, George AA, and Jha A completed the manuscript; Mishra AK, Sharma N, Sargent J, and Kranis MJ reviewed the manuscript; Kranis MJ approved the manuscript.
Institutional review board statement: This protocol was developed, reviewed, and sanctioned by the joint institutional review board at MetroWest Medical Center under Approval No. 2019-171.
Informed consent statement: The ethical requirement for individual informed consent was appropriately waived by the institutional review board due to the retrospective nature of this study.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ajay Kumar Mishra, MD, Academic Fellow, Division of Cardiology, Saint Vincent Hospital, 123 Summer Street, Worcester, MA 01608, United States. ajaybalasore@gmail.com
Received: February 4, 2024
Revised: April 27, 2024
Accepted: May 15, 2024
Published online: June 26, 2024
Processing time: 141 Days and 16.3 Hours

Abstract
BACKGROUND

Infective endocarditis (IE) is a life-threatening infection with an annual mortality of 40%. Embolic events reported in up to 80% of patients. Vegetations of > 10 mm size are associated with increased embolic events and poor prognosis. There is a paucity of literature on the association of multiple vegetations with outcome.

AIM

To study the echocardiographic (ECHO) features and outcomes associated with the presence of multiple vegetations.

METHODS

In this retrospective, single-center, cohort study patients diagnosed with IE were recruited from June 2017 to June 2019. A total of 84 patients were diagnosed to have IE, of whom 67 with vegetation were identified. Baseline demographic, clinical, laboratory, and ECHO parameters were reviewed. Outcomes that were studied included recurrent admission, embolic phenomenon, and mortality.

RESULTS

Twenty-three (34%) patients were noted to have multiple vegetations, 13 (56.5%) were male and 10 (43.5%) were female. The mean age of these patients was 50. Eight (35%) had a prior episode of IE. ECHO features of moderate to severe valvular regurgitation [odds ratio (OR) = 4], presence of pacemaker lead (OR = 4.8), impaired left ventricle (LV) relaxation (OR = 4), and elevated pulmonary artery systolic pressure (PASP) (OR = 2.2) are associated with higher odds of multiple vegetations. Of these moderate to severe valvular regurgitation (P = 0.028), pacemaker lead (P = 0.039) and impaired relaxation (P = 0.028) were statistically significant. These patients were noted to have an increased association of recurrent admissions (OR = 3.6), recurrent bacteremia (OR = 2.4), embolic phenomenon (OR = 2.5), intensive care unit stay (OR = 2.8), hypotension (OR = 2.1), surgical intervention (OR = 2.8) and device removal (OR = 4.8). Of this device removal (P = 0.039) and recurrent admissions (P = 0.017) were statistically significant.

CONCLUSION

This study highlights the associations of ECHO predictors and outcomes in patients with IE having multiple vegetations. ECHO features of moderate to severe regurgitation, presence of pacemaker lead, impaired LV relaxation, and elevated PASP and outcomes including recurrent admissions and device removal were found to be associated with multiple vegetations.

Key Words: Endocarditis, Echocardiography, Vegetations, Predictors, Outcome

Core Tip: Embolic events occur in up to 80% of patients with infective endocarditis (IE). Vegetations of > 10 mm in size are associated with increased embolic events and poor prognosis. In this retrospective cohort study, patients diagnosed with IE were recruited over 2 years. 34% of these had multiple vegetations. Echocardiographic features of moderate to severe regurgitation, presence of pacemaker lead, impaired left ventricle relaxation, and elevated pulmonary artery systolic pressure were associated with higher odds of multiple vegetation and outcomes including recurrent admissions and device removal were found to be associated with multiple vegetations.



INTRODUCTION

Infective endocarditis (IE) is a life-threatening infection with an annual mortality of 40%. The complications of this disease are protean, with embolic events reported in up to 80% of patients[1]. There are several epidemiological, clinical, microbiological risk factors that contribute to adverse outcomes in patients with IE. Transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) are the most effective diagnostic tools for IE. Even though used for diagnosis, the role of echocardiography in predicting outcome in these patients is still limited. Large vegetation size especially vegetations of > 10 mm size has been shown to be associated with increased embolic events and poor prognosis[2]. In patients with Staphylococcus aureus IE, ejection fraction of less than 40%, and intra-cardiac abscess has been shown to predict in-hospital mortality and perforation of valve[3-5]. Intra-cardiac abscess has been shown to independently predict 1-year mortality. There is a paucity of literature on the association of multiple vegetations with the outcome. The main objective of our study was to study the echocardiographic (ECHO) features associated with the presence of multiple vegetations and the implications of the presence of multiple vegetations on the outcome.

MATERIALS AND METHODS

In this retrospective, single center, cohort study patients diagnosed with IE were recruited from June 2017 to June 2019 from a community based tertiary care center in Massachusetts. All patients with microbiological and ECHO evidence of IE were eligible to be admitted to the study. Patients had to fulfill modified Duke’s criteria to be diagnosed have IE. Once diagnosis of IE was established, patients were further subdivided as cases and controls based on presence or absence of multiple vegetations (defined as presence of 2 or more vegetations as identified in ECHO).

Instruments and protocols

For echocardiography GE (Vivid E95 model), Philips (Epic CVx3D model) machines were used. TTE for these patients were performed by skilled, American Society of Echocardiography (ASE) certified echocardiographers. During echocardiography qualitative and quantitative images of all 4 cardiac chambers, valves, vegetations, intra-cardiac complications were obtained. Subsequently, echocardiography was analyzed by 2 independent skilled cardiologists. Initial diagnostic modality was TTE, subsequently TEE was done based on further clinical requirements.

Definitions

The following definition was used to define ECHO variables. The key papers of the ASE were used to define chamber quantifications, severity of valvular dysfunction, vegetation and diastolic dysfunction as discussed below: (1) Vegetation: 2019 American College of Cardiology/American Heart Association/ASE report defined vegetation as a mass present on a valve or its adjacent structure related to infective or collagen vascular (inflammatory) endocarditis[6]. Multiple vegetations: Defined as more than one vegetation visualized in multiple echocardiography views; (2) Valvular abnormalities: ECHO evidence of leaflet perforation, leaflet destruction, leaflet prolapse, leaflet mal coaptation, flail leaflet, valvular stenosis, and regurgitation in the presence of vegetations were defined as valvular abnormalities; (3) Valvular regurgitation: The overall interpretation of the severity of valvular regurgitation was based on the integration of all information obtained during the imaging study[6]. Acceptable degrees to describe severity of valvular regurgitation are outlined below: None - regurgitant flow is not present. Trace - minimal leakage valve is present. Mild - mild leakage of the valve is present. Mild to moderate - mild-to-moderate leakage of the valve is present. Moderate - moderate leakage of the valve is present. Moderate to severe - moderate-to-severe leakage of the valve is present. Severe - severe leakage of the valve is present; (4) Low ejection fraction: Male < 52%, female < 54% as per ASE chamber quantifications guidelines[7]; (5) Impaired left ventricle (LV) relaxation: Left ventricular diastolic function is defined by ASE as relaxation and filling during the period after aortic valve closure and before aortic valve opening. Assessment of left ventricular diastolic function includes evaluation of relaxation and compliance, using mitral inflow patterns, annular tissue Doppler velocities, tricuspid regurgitation velocity, left atrial size and pulmonary vein flow velocities[6,7]; and (6) Elevated pulmonary artery systolic pressure (PASP): As per ASE definitions, mean pressure in the pulmonary arteries ≥ 25 mmHg at rest or 30 mmHg during physical activity based on assessment of the tricuspid regurgitation jet velocity suggests probable presence of pulmonary hypertension[7].

Outcome measures

During this period a total of 84 patients were diagnosed to have IE. Sixty-seven patients with ECHO evidence of vegetation were identified. Baseline demographic, clinical, laboratory and ECHO parameters were obtained. ECHO images of these patients were reviewed for findings such as valvular abnormalities including leaflet perforation, leaflet aneurysm, flail leaflet, valvular obstruction, regurgitation, paravalvular abscess, intracardiac abscess, pseudoaneurysm, fistula, prosthetic valve dehiscence, low ejection fraction, pacemaker wire vegetation, and pericardial effusion. Outcomes that were studied included recurrent admission, recurrent bacteremia, requirement of prolonged antibiotics, embolic phenomenon, hypotension, requirement of intensive care unit (ICU) stay, mechanical ventilation, removal of device, requirement of surgical intervention and mortality. Subsequent admission for the same clinical diagnosis or its complications was defined as recurrent admissions. Repeat isolation of the prior organism with presence of bacteremia was defined as recurrent bacteremia. Requirement of longer duration of antibiotics for persistence of bacteremia was defined as prolonged antibiotics use. Definitions of outcome variables: Recurrent admission: Defined as readmission for clinical diagnosis or complications related to the prior episode of IE. Recurrent bacteremia: Subsequent isolation of the initial organism with evidence of bacteremia. Prolonged antibiotics: Longer duration of antibiotics because of persistence of bacteremia (> 8 wk) or prior discontinuation. Embolic phenomenon: Occurrence of any new embolic event or occurrence of an embolic event at a different site during the hospital stay. Hypotension: Defined as persistent low systolic blood pressure of < 90 mmHg requiring fluid or pressors. ICU stay: Is defined as upgrading of care, in a specialized unit, for the need of cardiac or respiratory support with mechanical ventilation or pressors. Mechanical ventilation: Requirement of invasive and noninvasive mechanical ventilatory support. Removal of device: Requirement of removal of temporary intravenous cannula, and cardiac implantable electronic devices.

Data analysis

TTE imaging was obtained by skilled and ASE certified echocardiographers. TTE images were reviewed and reported by two trained cardiologist blinded towards the outcome. TEE was obtained and interpreted by a trained cardiologist. Clinical data was entered in a preformed proforma by 2 independent physicians. Data obtained were entered into Microsoft Excel version 22 (Microsoft Corp.Redmond, Washington) and were analyzed using IBM SPSS version 28 (IBM Corp., Armonk, New York). Continuous data were measured as mean, median, range, and percentage. The odds ratio (OR) was used to measure the association. We used the χ2 test to calculate the OR for categorical variables and unadjusted binary logistic regression to calculate the OR of continuous variables. A P value less than 0.05 was considered significant. Institutional review board approval was obtained before the initiation of the study.

RESULTS

Among the 67 patients 23 (34%) patients were noted to have multiple vegetations as shown in Figure 1. Among these 13 (56.5%) were male and 10 (43.5%) were female. The distribution of gender in both the subgroups were identical. Patients with multiple vegetations were older with the mean age of the patients with multiple vegetations being 50 as compared to 45 for the patients with single vegetation. Eight (35%) had a prior episode of IE. This was similar to the patients with single vegetation. Single vegetation occurred in higher percentage (84%) of patients with native valve IE. The tricuspid valve was involved in 9 (50%) patients with multiple vegetations and 21 (50%) patients in single vegetation. The mitral valve was involved in 4 (22%) patients with multiple vegetations and 12 (27%) patients with single vegetation. Multiple valvular involvement was noted in 4 (22%) patients with multiple vegetation. A higher percentage of patients with multiple vegetations had transesophageal echocardiogram (78%). Heart rate and left arterial volume were almost similar in both the groups. Higher PASP was noted in patients with multiple vegetations. However, none of the differences in the baseline demographic details were statistically significant as shown in Table 1. Valvular abnormalities including leaflet perforation, leaflet destruction, flail leaflet, and regurgitation were noted in around 10% of patients. The presence of prosthetic valve (26%), pacemaker lead (26%), impaired left ventricular relaxation (83%), and elevated PASP (48%) and moderate to severe valvular regurgitation (83%) were higher in patients with multiple vegetations. The presence of an indwelling catheter, low ejection fraction (< 50%), right and left atrial enlargement were equal in both the groups. ECHO features of moderate to severe valvular regurgitation (OR = 4), presence of pacemaker lead (OR = 4.8), impaired LV relaxation (OR = 4), and elevated PASP (OR = 2.2) were associated with higher odds of multiple vegetations. Of these, moderate to severe valvular regurgitation (P = 0.028), the presence of pacemaker lead (P = 0.039) and impaired relaxation (P = 0.028) were statistically significant (Table 2).

Figure 1
Figure 1 Strobe diagram showing the flow of the patients. IE: Infective endocarditis; ECHO: Echocardiographic.
Table 1 Baseline demographic parameters of the patients with multiple vegetation as compared to single vegetation.
Variable
Multiple vegetations (N = 23)
Single vegetation (N = 44)
OR
P value
Gender, n (%)10.98
    Female10 (43.5)19 (43)
    Male13 (56.5)25 (57)
Mean age (SD)50 (20.6)45 (18.6)1.010.33
Prior IE, n (%)8 (35)14 (32)1.10.8
Native valve IE, n (%)18 (78)37 (84)0.680.55
TTE (N = 49), n (%)11 (48)20 (45)0.910.8
TEE (N = 49), n (%)18 (78)30 (68)1.60.54
HR (SD)105 (18.5)106 (21.8)0.990.83
LAVI (SD)32 (11.7)30 (10.5)1.010.50
PASP (SD)38 (14.2)32.5 (10.9)1.030.10
Table 2 Baseline echocardiographic parameters of the patients with multiple vegetation as compared to single vegetation, n (%).
ECHO variable
Multiple vegetations (N = 23)
Single vegetation (N = 44)
OR
P value
Valvular abnormality2 (9)6 (14)0.6030.5
Moderate to severe regurgitation19 (83)24 (55)40.028a
Prosthetic valve6 (26)7 (16)1.90.32
Pacemaker lead6 (26)3 (7)4.80.039a
Indwelling catheter3 (13)10 (23)0.50.34
Low EF (EF < 50)2 (9)6 (14)0.60.55
RAE8 (35)13 (29.5)1.30.66
LAE8 (35)15 (34)10.95
Impaired LV relaxation19 (83)24 (55)40.028a
Elevated PASP11 (48)13 (29.5)2.20.1

Patients with multiple vegetation had increased percentages of requirement of prolonged antibiotics (30%), recurrent bacteremia (48%), recurrent admission (65%), embolic events (39%), requirement of ICU care (48%), hypotension (35%), requirement of mechanical ventilation (22%), removal of device (26%), and surgical intervention (35%) as shown in Table 3. Among these variables, higher odds of association (OR > 2) was present in recurrent admissions (OR = 3.6), recurrent bacteremia (OR = 2.4), embolic phenomenon (OR = 2.5), ICU stay (OR = 2.8), hypotension (OR = 2.1), surgical intervention (OR = 2.8), and device removal (OR = 4.8). However, only requirement of device removal (P = 0.039) and recurrent admissions (P = 0.017) were statistically significant. No significant difference in mortality was seen between the groups.

Table 3 Outcome of the patients with multiple vegetation as compared to single vegetation, n (%).
Outcomes
Multiple vegetations (N = 23)
Single vegetation (N = 44)
OR
P value
Prolonged antibiotics7 (30)9 (20.5)1.70.36
Recurrent bacteremia11 (48)12 (27)2.40.09
Recurrent admission15 (65)15 (34)3.60.017a
Embolic phenomenon9 (39)9 (20.5)2.50.1
Hypotension8 (35)9 (20.5)2.10.2
ICU stay11 (48)112.80.06
MV5 (22)7 (16)1.50.55
Removal of device6 (26)3 (7)4.80.039a
Surgical intervention8 (35)7 (16)2.80.08
Mortality1 (4)3 (7)0.60.68
DISCUSSION

IE is an infectious condition that affects the cardiac endocardial surface, most commonly cardiac valves. Annual incidence of 3-7 per 100000 years have been documented in previous population surveys[1,8]. A 20-year trend analysis showed a significant decrease in annual mortality percentage change between 2004 and 2010, but age- adjusted mortality has stabilized since 2010 till 2019 at 51 deaths per 100000 person-year[9]. Demographic factors including male sex, black population, older age (> 65 years old), and rural location were associated with a higher crude and adjusted mortality rates[9,10]. Mortality ranges from 3% to 14% during index hospital admission, which increases substantially to 36%-37% at 1-year follow-up[11].

Similarly, our study had a mortality of 3% to 7%. This systematic review also showed Staphylococcus aureus as the most common microbe encountered in IE like in our study. Other common pathogens include Enterococcus spp., Viridians Streptococcus and Coagulase- negative Staphylococci[5,11,12]. With recent developments in diagnostic investigations, including cultures and TEE, multiple organisms have been implicated in causing IE[12-14]. Based on an International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) of more than 2700 definite IE, native valve IE (72%) was most frequent followed by prosthetic valve IE (21%). Native valve endocarditis was noted in > 70% of patients in our study and > 30% patients had a remote history of IE. Vegetations were more common on the mitral valve (41%), followed by aortic (38%), and tricuspid (12%) valves[15,16].

Many risk factors including recent increase in bioprosthetic valves, use of cardiac prosthesis and grafts in adult patients with congenital heart diseases, and intravenous drug use (IVDU) with opioid epidemic are associated with increased incidence of IE. In our study 30% of patients had IVDU related IE. IVDU related increase has been seen more prominently in younger and uninsured population and associated with high health care expenditure burden[11]. A significant proportion, 6%-16%, require valvular surgery for IE thereby necessitating multidisciplinary care for this vulnerable patient population[11].

Predictors of poor outcomes in IE

Multiple epidemiological, clinical, microbiological, risk factors contribute to adverse outcomes in patients with IE. Embolization of vegetation is one of the feared complications of IE associated with poor prognosis, increased mortality, and increased health care utilization. Brain, spleen, lungs, coronaries, bowel, and extremities are some of the sites with highest predilection of getting affected by septic emboli. A vegetation size of 10 mm or more was associated with higher odds of systemic embolic events and all-cause mortality based on systematic review of 21 studies[3,17,18]. In our study embolic events occurred in 29% of study population, and was even higher in among patients with multiple vegetations (39%). Embolic events can complicate up to 80% of presentations. Pulmonary septic emboli are seen more commonly with right sided IE, whereas left sided IE embolizes frequently to brain and spleen. Embolic events are more prevalent with mitral vegetation of any size compared to aortic vegetation of similar size[19-21]. Anterior leaflet vegetations of mitral valve have increased propensity to detach and embolize in contrast to posterior leaflet vegetations[20]. Causative pathogens also affect embolic events incidence- more virulent microbes including Staphylococcus aureus and Candida are associated with higher rates[22,23]. Embolic phenomena are more common during the initial course of the disease, and decrease dramatically within 2-3 wk of appropriate antimicrobial therapy[22,24].

Metastatic sources of infection can develop from septic emboli [e.g., splenic abscess, mycotic aneurysms (MA)] which may require additional interventions. Extracranial and intracranial MA are life-threatening especially when they become symptomatic after rupture. They can often go undetected which underestimates their incidence. Overall mortality with intracranial MA approximates 60% based on few reports, with mortality approaching 80% when these aneurysms rupture[25-27].

In addition to embolization, local extension of infection beyond annulus of valve is dangerous. Perivalvular abscess and later fistulization or shunting between various cardiac chambers often require surgical intervention. These complications have been demonstrated to predict higher mortality, requirement of valvular surgery, pacemakers, and longer course of antibiotics[4,13,27,28]. Aortic valve vegetations are more likely to develop perivalvular abscess[5,13,29]. Among patients who survived, changes in acute physiology causing a change in APACHE-II score was seen, as compared to patients who did not. Similarly, the presence of heart failure at presentation, any stroke during disease course, diabetes mellitus, were independently associated with poor outcomes in a retrospective cohort study at a tertiary center[4]. Interestingly, cardiac surgery during admission did not affect mortality on multivariable analysis[4].

ECHO manifestations of vegetations in IE

Echocardiography remains cornerstone for diagnosis of IE. The evolution of imaging techniques in recent times that lead to an improvement of spatial image resolution have improved the sensitivity of this modality to detect vegetations. TTE is the preferred initial investigation unless device infection or prosthetic valve endocarditis is suspected[30]. TEE is the gold standard investigation. Vegetation visualization in real time for location, mobility, size, and associated local complications - valvular dehiscence, fistula, abscess makes echocardiogram a primary modality of imaging[30,31]. Multiple vegetations can be identified in TEE as it is able to differentiate smaller vegetations. In our study TEE was able to identify multiple vegetations in 78% of patients (Figure 2). Aortic valve vegetations are located on ventricular side of valve and have diastolic outflow tract prolapse. Similarly, mitral, and tricuspid valve vegetations are located on atrial side of leaflets and have tendency to prolapse into their respective atria in systolic phase. Endocardial involvement on echocardiogram is one of the major criteria in original and modified Duke’s criteria[32,33]. The presence of oscillating intracardiac mass, intracardiac abscess, new dehiscence of prosthetic valve, and new valvular regurgitation are the criteria to diagnose IE on echocardiogram. Duke’s criteria was modified to exclude patients with worsening or changing of pre-existing murmur as a criterion for diagnosis[32,33].

Figure 2
Figure 2 Echocardiographic images of vegetations.

Sensitivity and specificity of TTE for native valve endocarditis ranges from 50%-90% and 90% respectively[34]. The sensitivity is poor for prosthetic valve involvement at 29% while specificity was noted to be 100% in a systematic review[35]. In contrast, TEE has higher sensitivity and specificity reaching > 90% for native valve endocarditis[34]. However, sensitivity to detect prosthetic valve endocarditis is around 80% by TEE, with no difference in specificity compared to TTE[35]. Erbel et al[20] elucidated improved diagnostic accuracy of TEE over TTE as smaller vegetations were hard to discern on TTE. The presence of vegetations correlated with embolic events. Embolic events appear to occur more often with larger vegetations (> 10 mm) and location on mitral valve[17,20,36]. In our study, we also identified that higher proportions of patients noted to have multiple vegetations had undergone TEE. Echocardiography is crucial in identifying vegetations on pacemakers and defibrillators. TEE is instrumental in identifying the site, number, and extent of vegetations on cardiovascular implantable device (CIED). Vegetations on CIED can become large. Echocardiography is also used to detect complications associated with vegetations. The sensitivity to diagnose paravalvular abscess with TTE and TEE is 28% and 87%, respectively, while specificity is comparable at > 95% for both TTE and TEE[22]. Valve perforation is also better detected with TEE vs TEE (sensitivity 95% vs 45%) with specificity of > 95% for both modalities[37]. Valvular and paravalvular complications in our study subgroups were similar. This is in keeping with the prior literature showing lack of association between vegetation size and paravalvular complications[38].

ECHO features associated with outcomes of IE

Features visualized on echocardiogram can help to predict outcomes associated with IE and guide further management. As shown in Table 4 multiple ECHO parameters can predict outcome in patients with IE. A larger vegetation size (10 mm), mitral valve vegetation and anterior mitral leaflet involvement is associated with a higher odd of embolization, as described earlier. Vegetation size has been used as an independent ECHO predictor in Embolic Risk French Calculator[39]. However, caution should be maintained on discrepancy in cutoff size based on 3D vs 2D imaging as 3D imaging is more sensitive[40].

Table 4 Echocardiographic predictors of outcome in infective endocarditis.
Finding
Embolism
Morbidity
Mortality
Vegetation size1+++
Mitral valve location+++
Anterior leaflet of MV+--
Vegetation mobility2+--
Multiple vegetation++-
Cardiac device vegetations+++
Valvular complications3+++
Perivalvular complications4+++
Prosthetic valve vegetation+++
Prosthetic valve dehiscence+++

Vegetation mobility was noted to be an independent predictor of embolic events in an early study published in 2001[41]. Many studies have been published since then, and cumulative evidence suggests presence of mobile vegetation was associated with double odds of embolic events in a comprehensive systematic review. Vegetation mobility with displacement angle of > 60° is further associated with higher embolic events[42]. In addition, presence of multiple vegetations was independently associated with more embolic events, however, presence of bivalvular vegetations didn’t have statistical significance[43]. This was similar to our study where patients with multiple vegetations had higher odds of having embolic events.

The presence of large vegetation on CIED is known to increase hospital mortality. Similarly, CIED endocarditis is known to increase health care utilization, cost, need of intervention, surgical procedure and worsen quality of life similar to this study[44,45]. Valvular complications including leaflet perforation, flail leaflet, leaflet obstruction and acute valvular regurgitation can increase embolic events and morbidity and mortality in patients with IE. Demonstration of paravalvular complications including abscess, aneurysm, fistula and paravalvular regurgitation is associated with worst patient outcome. Presence of valvular and paravalvular complications is associated with increased odds of mortality and necessitating cardiac surgery and prolonged antibiotics[16]. In our study patients with multiple vegetations had higher odds of having severe valvular regurgitation and needing surgical intervention. There has been limited literature of implications of diastolic dysfunction in patients with endocarditis. While we found that impaired LV relaxation and elevated PASP was more among patients we are unable to conclude that elevated filling pressure and impaired LV relaxation was solely responsible for multiple vegetations.

ECHO features of IE, using modified Duke’s criteria, were present in 87% of patients in ICE-PCS study[16]. Approximately 60% of these subjects had undergone TTE and TEE, and 99.2% of the study population had undergone either TTE or TEE. The most common paravalvular complication was abscess formation, noted in 14% of patients. In one-third of the patients with prosthetic valve endocarditis, their courses were complicated by dehiscence or new regurgitation lesion. Presence of mitral valve vegetations, paravalvular complications and prosthetic valve endocarditis were associated with higher odds of mortality. Interestingly in our study, patients with multiple vegetations had higher requirement of prolonged antibiotics, recurrent bacteremia, recurrent admission, embolic events, requirement of ICU care, hypotension, requirement of mechanical ventilation, removal of device, and surgical intervention. Among these variables, the requirement of device removal and recurrent admissions were statistically significant. However, there was no difference in mortality.

The limitations of this study are the retrospective nature, small sample size and lack of matching. While septic embolism to the lungs occurs with tricuspid valve endocarditis, systemic embolization is predominant with left sided IE. Embolic events are higher with mitral valve IE in comparison to aortic valve IE for any vegetation size. We were not able to compare the relationship between multiple vegetations on the individual valve with embolic outcomes due to identical and higher percentages of tricuspid valve involvement in both groups and a smaller number of patient involvement in the other valvular groups. We also did not have details of cost of care, patients’ insurance details, lack of details on functional status at admission and at follow up which could independently affect outcome[21,44,46]. However, the strength of this study was inclusion of patients with definite IE and imaging evidence of vegetation in both the subgroups and identifying the predictors of multiple vegetations and their associated outcomes in patients with IE[47-49].

CONCLUSION

In conclusion, this study highlights the associations of ECHO features and its outcomes in patients with IE having multiple vegetations. TEE is better at identifying and characterizing multiple vegetations. ECHO evidence of moderate to severe regurgitation, presence of pacemaker lead, impaired LV relaxation, and elevated PASP were implicated with presence of multiple vegetations. IE patients with multiple vegetations can contribute to multiple comorbidities among which recurrent admissions and requirement of device removal are found to be statistically significant.

Footnotes

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Cardiac and cardiovascular systems

Country of origin: United States

Peer-review report’s classification

Scientific Quality: Grade B

Novelty: Grade B

Creativity or Innovation: Grade B

Scientific Significance: Grade B

P-Reviewer: Vyshka G, Albania S-Editor: Wang JJ L-Editor: A P-Editor: Yuan YY

References
1.  Correa de Sa DD, Tleyjeh IM, Anavekar NS, Schultz JC, Thomas JM, Lahr BD, Bachuwar A, Pazdernik M, Steckelberg JM, Wilson WR, Baddour LM. Epidemiological trends of infective endocarditis: a population-based study in Olmsted County, Minnesota. Mayo Clin Proc. 2010;85:422-426.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 135]  [Cited by in F6Publishing: 143]  [Article Influence: 10.2]  [Reference Citation Analysis (0)]
2.  Mishra A, Sahu KK, Abraham BM, Sargent J, Kranis MJ, George SV, Abraham G. Predictors, patterns and outcomes following Infective endocarditis and stroke. Acta Biomed. 2022;93:e2022203.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 4]  [Reference Citation Analysis (0)]
3.  Mishra AK, Sahu KK, Baddam V, Sargent J. Stroke and infective endocarditis. QJM. 2020;113:515-516.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 4]  [Cited by in F6Publishing: 4]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
4.  Chu VH, Cabell CH, Benjamin DK Jr, Kuniholm EF, Fowler VG Jr, Engemann J, Sexton DJ, Corey GR, Wang A. Early predictors of in-hospital death in infective endocarditis. Circulation. 2004;109:1745-1749.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 277]  [Cited by in F6Publishing: 270]  [Article Influence: 13.5]  [Reference Citation Analysis (0)]
5.  Bakhit A, Mishra AK, Choudhary K, Khaled Soufi M. Aortic root fistula complicating Austrian syndrome. Monaldi Arch Chest Dis. 2021;91.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
6.  Douglas PS, Carabello BA, Lang RM, Lopez L, Pellikka PA, Picard MH, Thomas JD, Varghese P, Wang TY, Weissman NJ, Wilgus R. 2019 ACC/AHA/ASE Key Data Elements and Definitions for Transthoracic Echocardiography: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Data Standards (Writing Committee to Develop Cardiovascular Endpoints Data Standards) and the American Society of Echocardiography. Circ Cardiovasc Imaging. 2019;12:e000027.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 14]  [Cited by in F6Publishing: 15]  [Article Influence: 3.0]  [Reference Citation Analysis (0)]
7.  Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28:1-39.e14.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6446]  [Cited by in F6Publishing: 8146]  [Article Influence: 905.1]  [Reference Citation Analysis (0)]
8.  Duval X, Delahaye F, Alla F, Tattevin P, Obadia JF, Le Moing V, Doco-Lecompte T, Celard M, Poyart C, Strady C, Chirouze C, Bes M, Cambau E, Iung B, Selton-Suty C, Hoen B; AEPEI Study Group. Temporal trends in infective endocarditis in the context of prophylaxis guideline modifications: three successive population-based surveys. J Am Coll Cardiol. 2012;59:1968-1976.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 255]  [Cited by in F6Publishing: 275]  [Article Influence: 22.9]  [Reference Citation Analysis (0)]
9.  Agha A, Nazir S, Minhas AMK, Kayani W, Issa R, Moukarbel GV, DeAnda A, Cram P, Jneid H. Demographic and Regional Trends of Infective Endocarditis-Related Mortality in the United States, 1999 to 2019. Curr Probl Cardiol. 2023;48:101397.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
10.  Dayer MJ, Quintero-Martinez JA, Thornhill MH, Chambers JB, Pettersson GB, Baddour LM. Recent Insights Into Native Valve Infective Endocarditis: JACC Focus Seminar 4/4. J Am Coll Cardiol. 2024;83:1431-1443.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
11.  Talha KM, Dayer MJ, Thornhill MH, Tariq W, Arshad V, Tleyjeh IM, Bailey KR, Palraj R, Anavekar NS, Rizwan Sohail M, DeSimone DC, Baddour LM. Temporal Trends of Infective Endocarditis in North America From 2000 to 2017-A Systematic Review. Open Forum Infect Dis. 2021;8:ofab479.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 5]  [Article Influence: 1.7]  [Reference Citation Analysis (0)]
12.  George AA, Singh T, Bhattad PB, Sherif AA, Mishra AK. Serratia endocarditis, uncommon organism, with significant complications. Monaldi Arch Chest Dis. 2023;93.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Reference Citation Analysis (0)]
13.  Mishra AK, Sahu KK, Lal A, Menon V. Aortic valve abscess: Staphylococcus epidermidis and infective endocarditis. QJM. 2020;113:211-212.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5]  [Cited by in F6Publishing: 6]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
14.  Sahu KK, Mishra AK, Lal A, Kranis M. An interesting case of expressive aphasia: Enterococcus faecalis-related infective endocarditis complicating as septic emboli. QJM. 2020;113:146-147.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 6]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
15.  Lalani T, Chu VH, Park LP, Cecchi E, Corey GR, Durante-Mangoni E, Fowler VG Jr, Gordon D, Grossi P, Hannan M, Hoen B, Muñoz P, Rizk H, Kanj SS, Selton-Suty C, Sexton DJ, Spelman D, Ravasio V, Tripodi MF, Wang A; International Collaboration on Endocarditis–Prospective Cohort Study Investigators. In-hospital and 1-year mortality in patients undergoing early surgery for prosthetic valve endocarditis. JAMA Intern Med. 2013;173:1495-1504.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 164]  [Cited by in F6Publishing: 182]  [Article Influence: 16.5]  [Reference Citation Analysis (0)]
16.  Murdoch DR, Corey GR, Hoen B, Miró JM, Fowler VG Jr, Bayer AS, Karchmer AW, Olaison L, Pappas PA, Moreillon P, Chambers ST, Chu VH, Falcó V, Holland DJ, Jones P, Klein JL, Raymond NJ, Read KM, Tripodi MF, Utili R, Wang A, Woods CW, Cabell CH; International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) Investigators. Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study. Arch Intern Med. 2009;169:463-473.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1676]  [Cited by in F6Publishing: 1510]  [Article Influence: 100.7]  [Reference Citation Analysis (0)]
17.  Mohananey D, Mohadjer A, Pettersson G, Navia J, Gordon S, Shrestha N, Grimm RA, Rodriguez LL, Griffin BP, Desai MY. Association of Vegetation Size With Embolic Risk in Patients With Infective Endocarditis: A Systematic Review and Meta-analysis. JAMA Intern Med. 2018;178:502-510.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 43]  [Cited by in F6Publishing: 61]  [Article Influence: 10.2]  [Reference Citation Analysis (0)]
18.  Chesdachai S, Esquer Garrigos Z, DeSimone CV, DeSimone DC, Baddour LM. Infective Endocarditis Involving Implanted Cardiac Electronic Devices: JACC Focus Seminar 1/4. J Am Coll Cardiol. 2024;83:1326-1337.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 1]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
19.  Konstadt SN, Louie EK, Shore-Lesserson L, Black S, Scanlon P. The effects of loading changes on intraoperative Doppler assessment of mitral regurgitation. J Cardiothorac Vasc Anesth. 1994;8:19-23.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 41]  [Cited by in F6Publishing: 41]  [Article Influence: 1.4]  [Reference Citation Analysis (0)]
20.  Erbel R, Rohmann S, Drexler M, Mohr-Kahaly S, Gerharz CD, Iversen S, Oelert H, Meyer J. Improved diagnostic value of echocardiography in patients with infective endocarditis by transoesophageal approach. A prospective study. Eur Heart J. 1988;9:43-53.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 237]  [Cited by in F6Publishing: 228]  [Article Influence: 6.3]  [Reference Citation Analysis (0)]
21.  Mishra AK, Sahu KK, Nagabandi S, Benotti J. Infective endocarditis with mitral leaflet perforation and multiple embolic infarcts. QJM. 2020;113:757-759.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 2]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]
22.  Vilacosta I, Graupner C, San Román JA, Sarriá C, Ronderos R, Fernández C, Mancini L, Sanz O, Sanmartín JV, Stoermann W. Risk of embolization after institution of antibiotic therapy for infective endocarditis. J Am Coll Cardiol. 2002;39:1489-1495.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 294]  [Cited by in F6Publishing: 274]  [Article Influence: 12.5]  [Reference Citation Analysis (0)]
23.  Mishra AK, Sahu KK, Lal A, Sujata M. Systemic embolization following fungal infective endocarditis. QJM. 2020;113:233-235.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 11]  [Article Influence: 2.8]  [Reference Citation Analysis (0)]
24.  Steckelberg JM, Murphy JG, Ballard D, Bailey K, Tajik AJ, Taliercio CP, Giuliani ER, Wilson WR. Emboli in infective endocarditis: the prognostic value of echocardiography. Ann Intern Med. 1991;114:635-640.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 275]  [Cited by in F6Publishing: 281]  [Article Influence: 8.5]  [Reference Citation Analysis (0)]
25.  Wilson WR, Giuliani ER, Danielson GK, Geraci JE. Management of complications of infective endocarditis. Mayo Clin Proc. 1982;57:162-170.  [PubMed]  [DOI]  [Cited in This Article: ]
26.  Bohmfalk GL, Story JL, Wissinger JP, Brown WE Jr. Bacterial intracranial aneurysm. J Neurosurg. 1978;48:369-382.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 192]  [Cited by in F6Publishing: 144]  [Article Influence: 3.1]  [Reference Citation Analysis (0)]
27.  Sahu KK, Mishra AK, Sherif AA, Doshi A, Koirala B. An interesting case of pacemaker endocarditis. Neth Heart J. 2019;27:585-586.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Reference Citation Analysis (0)]
28.  Blumberg EA, Karalis DA, Chandrasekaran K, Wahl JM, Vilaro J, Covalesky VA, Mintz GS. Endocarditis-associated paravalvular abscesses. Do clinical parameters predict the presence of abscess? Chest. 1995;107:898-903.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 83]  [Cited by in F6Publishing: 89]  [Article Influence: 3.1]  [Reference Citation Analysis (0)]
29.  Middlemost S, Wisenbaugh T, Meyerowitz C, Teeger S, Essop R, Skoularigis J, Cronje S, Sareli P. A case for early surgery in native left-sided endocarditis complicated by heart failure: results in 203 patients. J Am Coll Cardiol. 1991;18:663-667.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 94]  [Cited by in F6Publishing: 97]  [Article Influence: 2.9]  [Reference Citation Analysis (0)]
30.  Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Tleyjeh IM, Rybak MJ, Barsic B, Lockhart PB, Gewitz MH, Levison ME, Bolger AF, Steckelberg JM, Baltimore RS, Fink AM, O'Gara P, Taubert KA; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation. 2015;132:1435-1486.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1569]  [Cited by in F6Publishing: 1855]  [Article Influence: 206.1]  [Reference Citation Analysis (1)]
31.  Sahu KK, Doshi A, Mishra AK, Kranis M. A female with five chambers. Neth Heart J. 2020;28:174-175.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
32.  Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. Am J Med. 1994;96:200-209.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1650]  [Cited by in F6Publishing: 1501]  [Article Influence: 50.0]  [Reference Citation Analysis (0)]
33.  Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG Jr, Ryan T, Bashore T, Corey GR. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis. 2000;30:633-638.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2699]  [Cited by in F6Publishing: 2680]  [Article Influence: 111.7]  [Reference Citation Analysis (0)]
34.  Afonso L, Kottam A, Reddy V, Penumetcha A. Echocardiography in Infective Endocarditis: State of the Art. Curr Cardiol Rep. 2017;19:127.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 41]  [Cited by in F6Publishing: 38]  [Article Influence: 5.4]  [Reference Citation Analysis (0)]
35.  Habets J, Tanis W, Reitsma JB, van den Brink RB, Mali WP, Chamuleau SA, Budde RP. Are novel non-invasive imaging techniques needed in patients with suspected prosthetic heart valve endocarditis? A systematic review and meta-analysis. Eur Radiol. 2015;25:2125-2133.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 55]  [Cited by in F6Publishing: 68]  [Article Influence: 7.6]  [Reference Citation Analysis (0)]
36.  Mills MT, Calvert P, Lip GYH. Infective endocarditis: Five key developments. Trends Cardiovasc Med. 2024;.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
37.  De Castro S, Cartoni D, d'Amati G, Beni S, Yao J, Fiorell M, Gallo P, Fedele F, Pandian NG. Diagnostic accuracy of transthoracic and multiplane transesophageal echocardiography for valvular perforation in acute infective endocarditis: correlation with anatomic findings. Clin Infect Dis. 2000;30:825-826.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 47]  [Cited by in F6Publishing: 47]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
38.  Mahmoud K, Hammouda T, Kandil H, Mashaal M. Prevalence and predictors of aortic root abscess among patients with left-sided infective endocarditis: a cross-sectional comparative study. Egypt Heart J. 2020;72:62.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 7]  [Article Influence: 1.8]  [Reference Citation Analysis (0)]
39.  Hubert S, Thuny F, Resseguier N, Giorgi R, Tribouilloy C, Le Dolley Y, Casalta JP, Riberi A, Chevalier F, Rusinaru D, Malaquin D, Remadi JP, Ammar AB, Avierinos JF, Collart F, Raoult D, Habib G. Prediction of symptomatic embolism in infective endocarditis: construction and validation of a risk calculator in a multicenter cohort. J Am Coll Cardiol. 2013;62:1384-1392.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 97]  [Cited by in F6Publishing: 96]  [Article Influence: 8.7]  [Reference Citation Analysis (0)]
40.  Pérez-García CN, Olmos C, Islas F, Marcos-Alberca P, Pozo E, Ferrera C, García-Arribas D, Pérez de Isla L, Vilacosta I. Morphological characterization of vegetation by real-time three-dimensional transesophageal echocardiography in infective endocarditis: Prognostic impact. Echocardiography. 2019;36:742-751.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 14]  [Article Influence: 2.8]  [Reference Citation Analysis (0)]
41.  Di Salvo G, Habib G, Pergola V, Avierinos JF, Philip E, Casalta JP, Vailloud JM, Derumeaux G, Gouvernet J, Ambrosi P, Lambert M, Ferracci A, Raoult D, Luccioni R. Echocardiography predicts embolic events in infective endocarditis. J Am Coll Cardiol. 2001;37:1069-1076.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 299]  [Cited by in F6Publishing: 256]  [Article Influence: 11.1]  [Reference Citation Analysis (0)]
42.  Macarie C, Iliuta L, Savulescu C, Moldovan H, Gherghiceanu DP, Vasile R, Filipescu D, Candea V. Echocardiographic predictors of embolic events in infective endocarditis. Kardiol Pol. 2004;60:535-540.  [PubMed]  [DOI]  [Cited in This Article: ]
43.  Yang A, Tan C, Daneman N, Hansen MS, Habib G, Salaun E, Lavoute C, Hubert S, Adhikari NKJ. Clinical and echocardiographic predictors of embolism in infective endocarditis: systematic review and meta-analysis. Clin Microbiol Infect. 2019;25:178-187.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 14]  [Cited by in F6Publishing: 20]  [Article Influence: 3.3]  [Reference Citation Analysis (0)]
44.  Blomström-Lundqvist C, Traykov V, Erba PA, Burri H, Nielsen JC, Bongiorni MG, Poole J, Boriani G, Costa R, Deharo JC, Epstein LM, Sághy L, Snygg-Martin U, Starck C, Tascini C, Strathmore N. European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections-endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2020;41:2012-2032.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 60]  [Cited by in F6Publishing: 101]  [Article Influence: 33.7]  [Reference Citation Analysis (0)]
45.  George A, Alampoondi Venkataramanan SV, John KJ, Mishra AK. Infective endocarditis and COVID -19 coinfection: An updated review. Acta Biomed. 2022;93:e2022030.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
46.  Lauridsen TK, Park L, Tong SY, Selton-Suty C, Peterson G, Cecchi E, Afonso L, Habib G, Paré C, Tamin S, Dickerman S, Bayer AS, Johansson MC, Chu VH, Samad Z, Bruun NE, Fowler VG Jr, Crowley AL. Echocardiographic Findings Predict In-Hospital and 1-Year Mortality in Left-Sided Native Valve Staphylococcus aureus Endocarditis: Analysis From the International Collaboration on Endocarditis-Prospective Echo Cohort Study. Circ Cardiovasc Imaging. 2015;8:e003397.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 34]  [Cited by in F6Publishing: 36]  [Article Influence: 4.0]  [Reference Citation Analysis (0)]
47.  Baddour LM, Fuster V. Today's Infective Endocarditis: Not What You Learned in Medical School. J Am Coll Cardiol. 2024;83:1324-1325.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
48.  Singh T, Mishra AK, Vojjala N, John KJ, George AA, Jha A, Hadley M. Cardiovascular complications following medical termination of pregnancy: An updated review. World J Cardiol. 2023;15:518-530.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
49.  Thomas VV, Mishra AK, Jasmine S, Sathyendra S. Gram-negative infective endocarditis: a retrospective analysis of 10 years data on clinical spectrum, risk factor and outcome. Monaldi Arch Chest Dis. 2020;90.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 2]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]