IE is a fatal disease with high mortality despite novel diagnostic and therapeutic strategies. Timely and early diagnosis of IE remains a challenge. Our study was aimed to clarify the characteristics of IE patients who underwent a surgery over an 18-year period in our hospital and to identify factors related to the false-negative echocardiography results. To our knowledge, this is the largest, long-term study on IE performed in our region.
4.1 Features of patients in the surgery group
For non-surgery patients, we adopted the modified Duke criteria for diagnosis, but only those who met the criteria of “definite IE” or “suspected IE” could be enrolled to ensure the reliability of the collected data. For patients in the surgery group, beyond the clinical diagnostic criteria, pathological results played a more critical role as the gold standard for diagnosis. A subset of patients had been never considered to have IE until intraoperative findings of vegetations or intracardiac abscesses. In our study, patients who underwent surgery were more likely to have pre-existing valvular lesions (basic heart disease), heart murmurs and heart deficiency, and a relative lack of signs of infection (fever and positive blood culture results) and cerebrovascular events. Therefore, patients in the surgery group were less frequently classified as “definite cases,” and were more likely to be “suspected cases” before surgery.
By comparing differences between echocardiographic and surgical findings within the surgery group, we found that missed diagnosis by echocardiography was more likely when perivalvular abscesses and valve perforation developed or when vegetations affected both the mitral and aortic valves. This is a novel finding; one possible explanation is that the pre-existing valvular disease with structural abnormalities and calcification are more likely to affect both the mitral and aortic valves, which may affect echocardiographic observations.
The International Collaboration on Endocarditis-Prospective Cohort Study reported that the average in-hospital mortality of IE was 18% worldwide. In contrast, the in-hospital mortality of our study was 10.7%. The mortality of patients who underwent surgery was almost one-sixth of that of patients who did not undergo surgery in our study. Several previous studies pointed out that surgery was independently associated with a lower risk of in-hospital mortality [14, 15]. We previously performed a multivariate analysis in 313 cases of IE (including prosthetic valve endocarditis) and identified intravenous drug addiction, prosthetic valve endocarditis, hemorrhagic stroke, acute congestive heart failure, renal insufficiency, left-sided endocarditis, and early surgery as independent predictors of in-hospital mortality. According to this data, we concluded that the surgery and less frequent occurrence of hemorrhagic stroke were protective factors for good prognosis of IE in the surgery group. This finding highlights that surgery is a crucial treatment for improving prognosis.
4.2 Factors related to the false-negative results of echocardiography
Our false-negative TTE rate was 14.5%, similar to other studies[7, 16]. Previous reports indicated that an echocardiographic diagnosis of endocarditis may be correct but sometimes incomplete[16, 17]. Regardless of the possible error in subjective assessments and operation caused by ultrasound technicians, the most common explanations for false-negative or erroneous echocardiographic results are atypical position of the vegetations, and small vegetations. Our findings were in line with the previous conclusions.
Both TTE and TOE may produce false-negative results if vegetations are small or have embolized. Many embolic events occur during the first two weeks after initiation of antibiotic therapy. The key point is the beginning of antibiotic treatment before surgery. In this circumstances it is important to specify the management of antimicrobial therapy and order an echocardiography at early time.
The multivariate analytic results showed that congenital heart disease and vegetation size <10 mm were risk factors for false-negative echocardiographic results, while fever and heart murmurs were protective factors. The latter two factors are typical manifestations of infective endocarditis and might cause alarm among clinicians, thus affecting the echocardiographic diagnosis.
Clinicians must be aware that echocardiography sensitivity is not 100%, and negative echocardiography results do not rule out IE. Sometimes echocardiography should be repeated several times. Significant progress in echocardiography has taken place in the last decades transitioning from 2-dimensional (2D) imaging to the increasing role of 3-dimensional (3D) imaging modality. The real‐time 3D TOE is recommended as it allows better characterization of IE vegetation.
Some studies have pointed out that the diagnostic sensitivity of TTE in S. aureus-related IE is significantly lower, while TEE significantly improves the diagnostic sensitivity . However, another publication expressed reservations. Our study also attempted to explore the effect of blood culture results on the accuracy of echocardiographic diagnosis of IE, but the results were not satisfactory. In our previous study, we mentioned that the blood culture positive rate of IE in our hospital was only 58.2% due to antibiotic abuse and other reasons, which was roughly consistent with the results of the present study. We speculated that this might affect the univariate analysis results.
Pathological examination of cardiac valves remains the gold standard for IE diagnosis. However, 9 cases of definite IE in our study did not meet the pathological diagnosis criteria. Detachment or disintegration of small vegetations after antibiotic therapy probably responsible for the false negative results of pathological results. In the absence of pathological evidence, the sensitivity of clinical diagnosis of IE using the modified Duke's standard alone is ~80%. Still, Duke's standard is also an important reference when we fail to obtain ideal pathological results.
Whether in the surgery or non-surgery group, the sensitivity of TTE remains a question. Factors related to false-negative echocardiographic results were also existed in non-surgical group. Therefore, the study was meaningful for both the surgical group and the non-surgical group.
Besides, the value of integrated diagnostic strategies using multimodality imaging is emerging. The multimodality imaging has assumed a pivotal role in the clinical decision making. As echocardiography has several limitations, the integration with other imaging modalities (computed tomography, magnetic resonance imaging, nuclear imaging) becomes often necessary.
This was a single-center study performed in a general teaching hospital, so the findings may not be applicable to all populations and areas. Besides, referral bias should be taken into consideration when describing the echocardiographic and surgical outcomes of IE, as patients with more complicated and serious illness were more likely to be treated at a tertiary hospital. Finally, the echocardiographic and pathological results are somewhat subjective, making detailed comparisons difficult.