Infective endocarditis (IE) is a diagnostic and therapeutic challenge that is associated with high patient morbidity and mortality. 1 The diagnosis and management of IE have changed dramatically over the past 40 years, in particular the complementary use of echocardiography. 23 In addition to positive blood cultures and a new regurgitant murmur, echocardiographic findings has become one of the major Duke criteria for IE providing objective evidence of endocardial involvment. 3 Despite the higher sensitivity and specifity of transesophageal echocardiography (TEE) in the detection of valvular vegetations and characterization of complications, 4567 transthoracic echocardiography (TTE) remains the initial procedure of choice in patients with suspected IE, due to its noninvasive nature and low cost. 8

Although echocardiography has been incorporated into the diagnostic approach for patients with suspected IE, systematic usage in clinical practice is still not optimally defined. In patients with a high clinical likelihood of IE, the practical role of TTE for diagnostic purposes is low. 910 In the same context, echocardiography is often requested for patients with a transient fever, a nonregurgitant murmur, or both, who have a very low likelihood for the disease, with a low diagnostic yield. 910 Strict adherence to indications for TTE and TEE may help to facilitate more appropriate use and accurate diagnosis in patients who are most likely to benefit from screening echocardiography, in those patients with intermediate likelihood of the disease. 10

Echocardiography using harmonic imaging (HI) is based on the principle of receiving double the emitted ultrasound frequency (fundamental and harmonic signals), separating out the two components, and processing the harmonic signal alone. 11 The properties of these harmonic signals are such that one can obtain significant improvements in spatial and contrast resolution, in particular of valvular structures, such as in the evaluation of suspected IE. 11 We thus sought to determine the diagnostic accuracy of detecting vegetations using harmonic transthoracic echocardiography (hTTE) as compared to TEE in patients with a intermediate likelihood of native valve IE at a Canadian tertiary care university hospital.

Echocardiography is the primary technique for the detection of vegetations and cardiac complications resulting from IE. 2 Echocardiography provides one of the major Duke criteria including: (1) presence of vegetations defined as mobile echo-dense masses implanted in a valve or mural endocardium; (2) presence of abscess; or (3) presence of a new dehiscence of a valvular prosthesis. 313 The observation from this study is that in patients with an intermediate likelihood of native valve IE, TTE with harmonic imaging provides diagnostic quality images for detecting the presence or absence of vegetations in the majority of cases. Harmonic transthoracic echocardiography has excellent concordance with TEE imaging, and should be recommended as the first line test in this select patient population. If the clinical suspicion remains intermediate to high, however, or the hTTE remains equivocal due to structural abnormalities or poor acoustic windows, TEE imaging should be pursued.

Harmonic imaging has been in clinical use for over half a decade, emerging as a promising additional modality in echocardiography. 1112 Harmonic imaging are disturbances of lower amplitude and higher frequency than the original vibration and when isolated, have frequencies of exact multiples of the fundamental frequency. 12 hTTE makes use of the second harmonic (twice the fundamental frequency) to minimize artefactual echoes that occur from indistinct tissue-tissue and tissue-blood interfaces. 12 As such, hTTE creates a cleaner echo signal with increased signal to noise ratio and improvement in lateral resolution (20–50%), at the cost of a reduction in axial resolution (40–100%). 14

Transthoracic echocardiography using harmonic imaging has been extensively used in the clinical setting to enhance endocardial visualization, mitral valve assessment, and reproducibility of left ventricular systolic function, 151617 but little is known about its use in the setting of suspected IE. In patients with a high pretest likelihood of IE (table 1), the practical role of TTE for diagnostic purposes is low, yet for prognostic purposes, it is useful for identifying perivalvular complications and assessing the severity of regurgitation. 910 Similarly, in patients with a low likelihood of disease who present with a transient fever and or nonregurgitant murmur, TTE has a low diagnostic yield, and an alternative diagnosis should be sought. 910

The current study supports the use of hTTE in the setting where patients have an intermediate likelihood of suspected IE. If the image quality is interpretable using hTTE (>80% of our population), the concordance rate using TEE as the gold standard is high. These patients should be initially screened with hTTE to confirm the diagnosis, and if positive, treated appropriately. When the images are of good quality on hTTE and the study is negative, one should entertain an alternate diagnosis. TEE should be reserved for those patients with an indeterminate hTTE or in positive studies with high risk features.

The impact of hTTE has been recently evaluated for the detection of vegetations as compared to fundamental TTE and TEE, in a population predominantly of intermediate to high likelihood of IE. 18 Their overall sensitivity for identifying vegetations using hTTE of 82%, specificity of 98%, NPV of 95% and PPV of 93% was slightly higher as compared to our study. 18 As the pretest likelihood of IE was higher in their population, a stronger concordant rate between hTTE and TEE of 0.95 (χ² = 126, df = 4, r = 0.85 with p < 0.001) was detected. 18 Our population is more representative however of those patients in the intermediate pretest category of IE, who are most likely to benefit from screening echocardiography. In addition it was demonstrated that hTTE had greater sensitivity for the detection of vegetations on prosthetic valves, when compared to fundamental imaging. 18 Our study evaluated only those individuals with suspected native valve IE, as TEE should be reserved as the primary diagnostic imaging modality in patients with suspected prosthetic valve endocarditis. We did not, however, compare fundamental imaging using TTE in to hTTE in our population as experienced observers can readily distinguish the two forms of imaging leading to unblinding and potential bias. In comparison to TEE as the gold standard thus, hTTE was able to detect the presence of vegetations with high diagnostic accuracy in a population of intermediate likelihood of IE.

Echocardiography is an integral diagnostic modality in patients with suspected IE. The choice of initial mode of echocardiography is dependent on multiple factors including the patient's risk, native versus prosthetic valve and the pretest likelihood of infection. 19 Our study adds to the growing body of data supporting the role of initial TTE with harmonic imaging in patients with an intermediate likelihood of IE.