Valve Strands in Patients With Infective Endocarditis

Infective endocarditis (IE) is a life-threatening disease even in the era of modern cardiac surgery and advanced antimicrobial therapy [1]. Echocardiography remains the first-line imaging modality for the diagnosis of IE [2]. Cardiac lesions compatible with vegetations, perivalvular abscesses, valvular or leaflet perforation or aneurysm, pseudoaneurysm, intracardiac fistula, significant new valvular regurgitation, or new prosthetic valve dehiscence are established as major diagnostic criteria for IE [3–5]. Transesophageal echocardiography (TEE) is highly recommended in cases of suspected IE with negative transthoracic echocardiography (TTE), in suspected prosthetic valve endocarditis (PVE), or in ΙΕ in cardiac implantable electronic devices (CIEDs) [3–5]. However, abnormal structures detected by TTE or TEE, including valve strands, might be misdiagnosed as IE-related vegetations, leading to prolonged hospitalization and unnecessary antimicrobial treatment [6, 7]. Valve strands, or Lambl's excrescences, are thin, filamentous, linear, and mobile structures with independent motion identified, mainly by TEE. They are more frequently observed in elderly patients with valves' degeneration and in prosthetic valves, especially during the first postoperative months, and they carry an increased risk of embolism, although they may also remain asymptomatic [6]. Evaluation of their clinical significance is challenging, especially in patients with suspected IE, because they can mimic vegetations despite having some different echocardiographic features [2, 6]. To investigate the clinical relevance of valve strands in patients with IE, Tzimas et al conducted a retrospective study involving 305 patients with bacteremia, with or without IE, and valve strands on echocardiography. Importantly, 2 senior expert cardiologists reviewed and assessed all echocardiographic studies in patients with suspected IE [8]. Reclassification of 27% of valve strands as vegetations by TEE upgraded cases of bacteremia to IE and underscored the complexity of echocardiography-based diagnosis, as well as the need for double-checking by experts in the field within a broader microbiological and clinical context of the disease [8]. Both the performance and interpretation of echocardiographic data require meticulous attention to detail, as well as expertise in cardiac imaging [2, 7]. For this purpose, strict prerequisites for echocardiography laboratory accreditation and guidelines for advanced cardiovascular imaging training have been introduced [9, 10]. Despite its retrospective nature, this study is the first to evaluate the clinical burden of well-defined valve strands in patients with bacteremia with and without IE. The clinical features of the study population (advanced age, high frequency of Staphylococcus aureus bacteremia, and a 27% mortality rate) corroborated the typical pattern of IE observed in Western countries. However, mortality and bacteremia relapse rates were comparable between the IE and non-IE groups of the study. In the subcohort of patients with IE and valve strands as the sole echocardiographic finding, without any other typical IE lesions (n = 38/101; Supplementary Table 1), rates of embolic events, mortality, and bacteremia relapse were similar to those observed in the non-IE group. Although not mentioned in the discussion, these results suggested that valve strands did not constitute, per se, an additional risk of embolism in patients with IE. Patients with valve strands but without typical echocardiographic findings of IE were classified as having IE based on other indicative features beyond echocardiography (ie, persistent bacteremia). The diagnosis of IE was established by a multidisciplinary team of experts in the field, who determined that the majority of patients with bacteremia and valve strands detected on echocardiography should not be classified as having IE. Therefore, prolonged hospitalization and intravenous treatment for IE based solely on the detection of valve strands were avoided. Moreover, a rapid switch from intravenous to oral antimicrobial therapy in patients with non-S. aureus bacteremia was feasible and safe. The low rates of bacteremia recurrence and/or IE in the study reflect the importance of early multidisciplinary validation of all diagnostic investigations in conjunction with clinical data in order to establish or exclude the diagnosis of IE [8]. However, treatment decisions in cases where IE is suspected but not confirmed still remain a major challenge in clinical practice. The retrospective single-center nature of the study, the mixed data regarding native valve endocarditis (NVE), PVE, and CIED-related infections, the lack of differentiation between early and late PVE, as well as the presence of complicated S. aureus bacteremia in the non-IE group requiring prolonged treatment, could have biased the study results, which therefore cannot be readily extrapolated. Moreover, the study design did not allow a comparison between patients with bacteremia/IE with and without valve strands in echocardiography. Differentiating between vegetations and valve strands is challenging, not only in the context of IE but also because both entities could carry a significant risk of embolism. The experience and skills of the performing and interpreting cardiologists, as well as the pretest probability of endocarditis, strongly influence echocardiographic findings, which may either support or refute a clinical suspicion of IE [2, 6, 7]. The timing of the examination is crucial for the diagnostic yield of IE; repeating the examination after initially negative studies in cases highly suspected of IE is strongly recommended in IE guidelines [3, 4]. Despite the overall high diagnostic sensitivity and specificity of TTE and particularly TEE, echocardiographic studies cannot always differentiate between vegetations caused by IE and those resulting from noninfectious conditions. Moreover, valvular thickening or calcifications, ruptured mitral chordae tendineae, and Lambl's nodules may also be confused with vegetations. Diagnostic accuracy is further impaired in prosthetic valves because of artifacts, highly echogenic sewing rings, and support structures, especially in recently implanted valves [2, 7]. Novel echocardiographic techniques have been developed, but their detailed analysis is beyond the scope of this commentary. Challenging clinical scenarios identified by echocardiography often require further evaluation using additional diagnostic modalities to establish the diagnosis of IE. Advances in cardiac imaging techniques, including [18F] FDG PET/CT and cardiac CT, have significantly improved the diagnostic accuracy of IE, especially in the presence of prosthetic material, then these imaging modalities are currently recommended in addition to echocardiographic studies [3–5]. However, they are not as widely available in clinical settings worldwide as echocardiography. Moreover, there is no ideal diagnostic imaging tool for IE; therefore, imaging findings should always be interpreted in conjunction with clinical, laboratory, and microbiological data by the multidisciplinary endocarditis team in order to synthesize the “mosaic” of IE diagnosis in challenging cases and guide appropriate treatment [1, 7, 8]. Few well-designed prospective clinical trials on IE exist. Data on IE are provided mainly by large epidemiological studies, such as the International Collaboration on Endocarditis (ICE) merged database and the European EURO-ENDO registry [11, 12]. Even though, the ICE echo-sub study focused only in patients with definite IE highlighting the prognostic role of cardiac lesions compatible with IE in the outcome of patients. No data on unclear or equivocal echocardiographic findings that led to a downgraded classification of IE were assessed [12]. There is an unmet need for holistic prospective multicenter multinational studies on suspected IE, collecting and analyzing stratified data in all clinical, microbiological, and imaging diagnostic and therapeutic aspects in different health-care settings. However, this clinical trial is highly challenging and difficult to perform also due to various diagnostic and therapeutic modalities throughout the world. A multidisciplinary endocarditis team composed of experts from different medical and surgical specialties that evaluates and validates clinical and research data on a case-by-case basis is highly recommended [1, 3, 5, 13]. The multidisciplinary team of experts in the field has been shown to improve the diagnosis and treatment of patients with IE while also reducing mortality [14]. The implementation and organization of a multidisciplinary team approach in the management of patients with IE should adapt to peculiarities and local needs of each Institution in order to achieve rapid and accurate diagnostic procedures, optimization of antimicrobial treatment and prompt surgical interventions in patients with IE [1, 3, 5, 7, 13]. Financial support. No financial support was provided.