Is There a Role for Tissue Doppler Imaging in Infective Endocarditis?

An 87-year-old woman was admitted to our Cardiology Department with symptoms and signs of acute congestive heart failure and fever. She had a long history of hypertension and chronic atrial fibrillation. Transthoracic echocardiography showed a large (>10 mm) and mobile mitral valve vegetation, prolapsing into the left ventricular inflow tract, with severe mitral regurgitation due to a perforation in the posterior leaflet, in a mitral valve with fibro-calcific degeneration. Mitral regurgitation was hemodynamically significant and a moderate-to-severe pulmonary hypertension was observed. Tissue Doppler Imaging recorded at the level of the vegetation detected its incoherent motion and measured the peak antegrade velocity, which was found to be almost four times higher than that sampled at the lateral mitral annulus. Blood cultures were negative for both aerobic and anaerobic microbes. During hospitalization, the patient developed a sudden onset of left-side hemiplegia. Diffusion-weighted magnetic resonance imaging demonstrated multiple hyperintense lesions involving both hemispheres, suggestive of a cardioembolism. Diagnosis of fungal endocarditis was made and a treatment with fluconazole was started. Successive echocardiograms showed a decrease in the size and mobility of the mitral vegetation, and an increase in its echo intensity. However, in view of the systemic conditions severely affected, the patient was treated conservatively and died 3 months later. In our patient echocardiography played a key role for a better definition of the clinical course. In this context, Tissue Doppler Imaging might provide an adjunctive parameter for the prediction of embolic risk from endocardial vegetations: the peak antegrade velocity recorded at the level of the vegetation. However, before being adopted in clinical setting, this parameter should be validated by adequately powered prospective studies.

CLINICAL COURSE

On August 15th, 2013, an 87-year-old woman was admitted to our Cardiology Department with symptoms and signs of acute congestive heart failure and fever. She had a long history of hypertension and chronic atrial fibrillation.

Electrocardiogram showed an atrial fibrillation with normal intraventricular conduction and a controlled ventricular rate (heart rate 68 bpm).

Chest X-rays revealed cardiomegaly with bilateral hilar congestion.

Blood tests documented neutrophilic leukocytosis (white blood cells 26,000/ml) and high levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP; 11,000 pg/ml), inflammatory markers (eritrosedimentation rate 40 mm and C-reactive protein 17.6 mg/dl) and procalcitonin (0.21 ng/ml).

Transthoracic echocardiography detected a single large vegetation, >10 mm in length, with the same consistency as the myocardial echoes, with a small area of attachment to the atrial side of the lateral mitral valve annulus and with a rapid oscillating motion, prolapsing into the left ventricular inflow tract, and completely different to the surrounding tissue [Figure 1].

Figure 1

Transthoracic echocardiogram in the acute phase. Four apical chamber section. Single large vegetation with echogenicity similar to that of the myocardium and with a small area of attachment to the atrial side of the lateral mitral valve annulus. This mass showed a rapid oscillatory movement, prolapsing into the inflow tract of the left ventricle, clearly distinct from the normal pattern of valve movement. The result was a massive mitral regurgitation due to a perforation in the posterior leaflet, in a native mitral valve with fibrocalcific degeneration

It was associated with a severe mitral regurgitation due to a perforation in the posterior leaflet. A moderate-to-severe (3–4+/4+) tricuspid regurgitation, a significant caval venous congestion, and a moderate-to-severe pulmonary hypertension, with a systolic pulmonary artery pressure (PAPs) value of 60 mmHg, were diagnosed too. The left ventricle was hypertrophic (interventricular septum thickness 13 mm), had reduced endocavitary dimensions (end diastolic volume 30 ml/m2) and a slightly depressed global contractile function (ejection fraction, calculated using Simpson's method monoplane, was 48%).

Tissue Doppler Imaging (TDI) was performed simultaneously; placing the pulsed wave (PW) sample volume at the level of the mass, it detected its incoherent motion, a rapid irregular movement unrelated to the cardiac cycle or cardiac structures as a result of free oscillation, with a prolapse in the left ventricular inflow tract. Furthermore, PW-TDI precisely characterized the vegetation mobility, by measuring a peak antegrade velocity of 38.5 cm/s [Figure 2], almost four times higher than the one obtained placing the sample volume at the level of the lateral mitral valve annulus.

Figure 2

Pattern of pulsed wave-Tissue Doppler Imaging (PW-TDI) recorded at the level of the endocardial vegetation in the acute phase. Four apical chamber section. The vegetation exhibited a pattern of incoherent motion: an oscillatory movement, rapid and independent from the surrounding tissue, not related to the cardiac cycle. It was measured a peak antegrade velocity of 38.5 cm/s, about four times higher than that obtained at the lateral mitral annulus

Three subsequent blood cultures were found to be negative for both aerobic and anaerobic microbes.

The patient was initially treated with intravenous (IV) diuretics (furosemide 60 mg/day), then underwent antibiotic therapy with IV vancomycin (1,500 mg/day) and ceftriaxone (2 g/day), and suspected of having a fungal endocarditis, antifungal therapy with IV fluconazole (100 mg/day).

In the following days of hospitalization, the patient developed a sudden onset of left hemiplegia.

A cerebral computed tomography (CT) scan showed no areas of altered signal intensity, but magnetic resonance imaging (MRI) demonstrated multiple hyperintense lesions involving both hemispheres, suggestive of a cardioembolism [Figure 3].

Figure 3

Brain magnetic resonance imaging (MRI). Axial diffusion-weighted imaging (DWI) MRI sequences. In the context of a chronic vascular disease, multiple and bilateral hyperintense lesions, suggestive of a cardioembolism

Ongoing echocardiograms revealed a gradual decrease in the size of the mitral vegetation and an increase in its echo intensity [Figure 4]; a concomitant reduction in its mobility was assessed by PW-TDI [Figure 5].

Figure 4

Transthoracic echocardiogram performed after 2 weeks of intravenous antifungal therapy with fluconazole, in addition to antibiotic therapy with vancomycin and ceftriaxone. Four apical chamber section. Reduction in the size and increased echogenicity of endocardial vegetation, partially calcified, pedunculated, and no longer prolapsing into the inflow tract of the left ventricle

Figure 5

Pattern of PW-TDI obtained at the level of the mass after 2 weeks of intravenous antifungal therapy with fluconazole, in addition to antibiotic therapy with vancomycin and ceftriaxone. Significant reduction in motility of the vegetation (peak antegrade velocity of 6 cm/s)

However, a significant hemodynamically mitral regurgitation persisted.

Taking into account the serious clinical condition of the patient and the recent episode of embolic stroke, we agreed with cardiac surgeons to opt for medical therapy alone.

In the following weeks, the patient's conditions worsened and she died 3 months after the diagnosis.

DISCUSSION

Neurologic events occur in 20-40% of patients with infective endocarditis (IE), mainly through the embolic occlusion of cerebral arteries arising from endocardial vegetation.[1]

Echocardiography plays a key role in predicting embolic events.[2]

Several factors are associated with increased risk of embolism:

Vegetation size: patients with vegetation length >10 mm are at higher risk of embolism,[3] and this risk is even higher in patients with very large (>15 mm) and mobile vegetations;[4]

Vegetation mobility: from fixed to prolapsing;[5]

Vegetation consistency: calcified lesions do not have embolic potentiality; those with a consistency equal or inferior to that of myocardial echoes are associated with increased risk of embolic complications;[6]

Vegetation extent: involvement of a single valve leaflet (particularly the location on the mitral valve) or multiple valve leaflets, the extension to extravalvular structures;[7]

The increasing or decreasing size of the vegetation under antibiotic therapy;[8]

Particular microorganisms (Staphylococci[9], Streptococcus bovis[10], Candida spp.);

Previous embolism;[8]

Biological markers.[11]

In the present case, clinical features of the patient (old and weakened), negative blood cultures, the vegetation's large size, and the response to antifungal therapy with IV fluconazole, suggested a diagnosis of fungal endocarditis.

The risk of embolization in cases of fungal endocarditis is very high; in fact, many authors recommend early surgical intervention in this situation to avoid neurological complications.[12]

PW-TDI is an echocardiographic technique, introduced by Isaaz et al.,[13] and Mc-Dicken et al.,[14] in the early 1990s, with a high temporal resolution.

It permits to obtain high-quality Doppler signals and a rapid quantitation of velocity, acceleration, and displacement of different ventricular wall segments.

Moreover, PW-TDI is able to discriminate the fine movements of intracardiac masses, and in particular, to identify endocardial vegetations by their characteristic pattern of incoherent motion.[15]

This pattern is due to the free oscillation of an anomalous structure, with velocity and direction of movement independent from and completely different than the surrounding tissue and without any correlation to the cardiac cycle.

Although PW-TDI suffers from some limitations (the need for manually performed mapping; a limited spatial resolution; identification of anomalous structures may be difficult due to the superimposed color), in our opinion these critical cautions should not decrease its potential utility in clinical practice.

In our case, placing the PW-TDI sample volume at the level of the mitral valve vegetation, made it possible to precisely measure its motility, by means of the peak antegrade velocity: This was found to be about four times higher than that sampled at the lateral mitral annulus. Despite the absence of standardized criteria of increased velocity in the clinical practice, we hypothesize that PW-TDI might provide an adjunctive echocardiographic parameter for prediction of embolic risk in IE: the peak antegrade velocity recorded at the level of the vegetation.

However, before being adopted in clinical setting, this parameter should be validated by adequately powered prospective studies.