**5. Diagnostic accuracy**

#### **5.1. M-mode echocardiography**

The first moving pictures of the heart using an ultrasound reflectoscope were recorded and published in 1953, by the 'father of echocardiography' Inge Edler, along with physicist Hellmuth Hertz. This led to the development of the standard time–motion (M-mode) ultrasonoscope, which later became known as an echocardiogram and depicted a single-imaging dimension displayed along a time axis [47].


Vg's = vegetations; TTE = transthoracic echocardiography; TEE = transesophageal echocardiography; NV = native valve; PV = prosthetic valve; n = number; Sx = surgery; path = pathological diagnosis, either surgical tissue or at autopsy; AV = aortic valve; MV= mitral valve; PPM = pacemaker lead; sens = sensitivity; spec = specificity; D = definite vegetations seen on echocardiography; P = possible vegetations in addition to definite vegetations seen on echocardiography. \*Includes studies using biplane and/or multiplane TEE; # total number included vegetations and/or abscesses detected by TEE

**Table 1.** Diagnostic accuracy of TTE and TEE for detection of predominantly left-sided cardiac vegetations, pre harmonic era TTE imaging.

The first study to demonstrate vegetations using M-mode echocardiography was published in 1973 [48], followed by a case report of a tricuspid valve vegetation detected in 1974 [49]. Early work demonstrated M-mode was able to detect approximately one-third of native valve vegetations in patients with a clinical and/or pathological diagnosis of IE [50, 51].

Real-time 2D and 3D echocardiographic imaging, along with color and spectral Doppler capabilities, has superseded M-mode. The culmination of these advancements has enabled echocardiography to emerge as the imaging gold standard for IE and as such, be incorporated into the modified Duke [2] as a major diagnostic criterion. M-mode now contributes little to imaging in IE, except to demonstrate the typical vibrations of vegetations and/or prolapse of valvular tissue with high-temporal resolution (>1000 Hz cf. 30–60 Hz with 2D).


Vg's = vegetations; TTE = transthoracic echocardiography; TEE = transesophageal echocardiography; NV = native valve; PV = prosthetic valve; n = number; AV = aortic valve; MV= mitral valve; TV = tricuspid valve; n/a = not available; sens = sensitivity; spec = specificity; HI = harmonic imaging; FI = fundamental imaging. \*modality against which sensitivity of TTE was compared; ^Included both definite and intermediate likelihood of IE on echocardiography; # sensitivity of TTE for detection of native valve vegetations, excluding prosthetic intracardiac material.

**Table 2.** Diagnostic accuracy of TTE compared to TEE for detection of predominantly left-sided cardiac vegetations utilizing modern era tissue harmonic imaging.

#### **5.2. Transthoracic echocardiography**

In the early 1970s real-time, phased array 2D TTE transducer technology was introduced, providing spatial resolution and anatomical detail not previously seen. This provided not only the ability to identify vegetations like its predecessor M-mode, but to accurately describe the size, point of attachment and morphology of intracardiac masses [52].

#### *5.2.1. Vegetations*

**5. Diagnostic accuracy**

70 Contemporary Challenges in Endocarditis

**Reference No. of**

**Stafford et al. [53]** *n* = 62 *n* = 29

**Erbel et al. [54]** *n* = 96 AV = 15

**Mügge et al. [55]** *n* = 105 NV = 69

**Daniel et al. [36]** *n* = 126 PV = 33

**Shapiro et al. [56]** *n* = 64 NV+

**Lowry et al. [57]** *n* = 93 Clinical ±

**Irani et al. [58]** *n* = 134 *n* = 60#

abscesses detected by TEE

harmonic era TTE imaging.

**5.1. M-mode echocardiography**

dimension displayed along a time axis [47].

**No. of Vg or valves involved by gold standard\*** 

Sx/path

MV = 3 PPM = 1 Sx/path

PV = 22 Sx/path

Sx/path

PV = 30 TTE + TEE

TEE\*

path (*n* = 29)

**patients** 

The first moving pictures of the heart using an ultrasound reflectoscope were recorded and published in 1953, by the 'father of echocardiography' Inge Edler, along with physicist Hellmuth Hertz. This led to the development of the standard time–motion (M-mode) ultrasonoscope, which later became known as an echocardiogram and depicted a single-imaging

> **Sensitivity and specificity for Vg**

Vg's = vegetations; TTE = transthoracic echocardiography; TEE = transesophageal echocardiography; NV = native valve; PV = prosthetic valve; n = number; Sx = surgery; path = pathological diagnosis, either surgical tissue or at autopsy; AV = aortic valve; MV= mitral valve; PPM = pacemaker lead; sens = sensitivity; spec = specificity; D = definite

echocardiography. \*Includes studies using biplane and/or multiplane TEE; # total number included vegetations and/or

The first study to demonstrate vegetations using M-mode echocardiography was published in 1973 [48], followed by a case report of a tricuspid valve vegetation detected in 1974 [49]. Early

vegetations seen on echocardiography; P = possible vegetations in addition to definite vegetations seen on

**Table 1.** Diagnostic accuracy of TTE and TEE for detection of predominantly left-sided cardiac vegetations, pre

**NV (%)** 

**TTE TEE** 

**PV (%) NV +** 

sens – – 93 – – – spec – – 89 – – –

sens 63 – – 100 – – spec 98 – – 98 – –

sens D 68 27 58 94 77 90

spec – – – – – –

sens – 36 – – 82 – spec – – – – – –

sens – – 60 – – 87 spec – – – – – –

sens 50 17 36 100\* 83\* 93\* spec 78 94 83 89\* 95\* 91\*

sens 68 – – – – – spec 100 – – – – –

**NV (%)** 

P 90 36 77 100 86 97

**PV (%)**  **NV + PV (%)** 

**PV (%)** 

> During the 1980s and 1990s, numerous landmark studies were published comparing the diagnostic accuracy of TTE for identification of predominantly left-sided cardiac vegetations.

Transthoracic echo was shown to have a combined sensitivity of 36–93% for native and prosthetic valve vegetations and a specificity of 78–100% (**Table 1**).

#### *5.2.1.1. Harmonic tissue imaging*

Harmonic sound waves are reflected back to the transducer at twice the frequency of the transmitted wave (fundamental frequency) and are subject to less near-field distortion and side lobe artifact. This results in a better signal-to-noise ratio with superior image resolution [47]. Specifically, there is an improvement in endocardial definition and visualization of the cardiac valves. However, the valve leaflet tissue itself may appear abnormally thickened when viewed using harmonic imaging [59, 60].

A number of studies have revisited the question of diagnostic accuracy of TTE for identification of mostly left-sided native valvular vegetations by comparing findings directly with TEE using modern era tissue harmonic imaging (hTTE). It remains unclear if modern era TTE imaging has resulted in improved detection of vegetations for left-sided vegetations, due to the wide variation in results reported (**Table 2**).


TTE = transthoracic echocardiography; TEE = transesophageal echocardiography; NV = native valve; PV = prosthetic valve; sens = sensitivity; spec = specificity; Sx = surgery; path = pathology, either confirmed with surgery or at autopsy. \*modality against which sensitivity and specificity of TTE and/or TEE was compared against. #Multiplane TEE probe transducer utilised for imaging in some or all patients in a study.

**Table 3.** Diagnostic accuracy of TTE and TEE for detection of abscess.

#### *5.2.2. Abscess*

Published data on diagnostic accuracy vary widely for abscess detection by TTE. Sensitivity has been reported at 28–81% with specificity 85–100% (**Table 3**). It is uncertain if harmonic imaging has positively impacted on the diagnostic accuracy, with some studies reporting no improvement [65, 68].
