Bubble echocardiography
Summary
In this follow-up to our previously published article on patent foramen ovale (holes in the heart) and stroke in the young, Dr Stephen Glen provides an overview of an innovative and emerging technique for detecting holes in the heart which may enable greater exploration of heart disease.
Key Points
- Echocardiography is improved by injecting bubbles during the procedure and watching their passage through the heart – bubble echocardiography.
- Intra-cardiac shunts (holes in the heart), such as patent foramen ovale, are detected particularly well by this investigation, but as yet the size of the shunt or the blood-flow involved cannot be determined reliably.
- Echocardiography is now the best initial investigation to detect patent foramen ovale in patients thought to have had an embolus pass through the heart to the brain (paradoxical embolus).
- Future developments using very small bubbles may allow a much greater exploration of heart diseases.
Declaration of interests: No conflict of interests declared
Intuitively it seems wrong to inject bubbles into patients, but cardiologists are increasingly using this technique during echocardiography to detect intracardiac shunts, and to define endocardial borders dependent on bubble size.
How it is done
By mixing a small amount of air in a suitable material, usually saline (salt water) or colloid, it is possible to generate an ultrasound contrast agent which reflects ultrasound energy strongly and is therefore easily distinguishable from surrounding blood and tissues. Successful ultrasound imaging requires detection of reflected ultrasound energy and this is most intense where there is an abrupt change in density, for example at the interface between a gas bubble and surrounding blood.
Typically 0·5ml of air is injected in a mixture which has been agitated between two syringes using a three way tap. Ideally, the injection should be through a large bore cannula in a proximal vein, for example in the brachial fossa, to maximise flow and minimise bubble disruption. The contrast injected will pass into the right side of the heart and should opacify the right atrium and ventricle before passing into the lungs where it is dissipated. The lungs have tremendous capacity to absorb and eliminate gas loads as has been demonstrated in animals and divers during explosive decompression. Contrast signals should not appear in the left side of the heart unless there is a right to left shunt, either in the heart or more rarely in the peripheral pulmonary circulation.
Detecting patent foramen ovale
Transthoracic echocardiography with second harmonic imaging is a good way to screen for intracardiac shunts, and the commonest such shunt occurs via a patent foramen ovale, present in around 25% of the normal population. Detection of bubbles in the left atrium is dependent on right to left shunting and actions such as coughing, the Valsalva manoeuvre or abdominal compression will transiently increase right atrial pressure compared with left and encourage shunting. Anatomically this may open a flap-like foramen ovale. Transoesophageal echoardiography is useful when examining the anatomy of the interatrial septum but is invasive and often requires sedation which reduces the subject’s ability to perform provocative manoeuvres. A further alternative is transcranial Doppler ultrasound using low frequency energy (typically 2MHz) to monitor the middle cerebral artery through the temporal bone. This is a sensitive but non-specific technique and gives no information about the site of shunting.
Functional significance of foramen ovale
Modern digital systems allow bubble examinations to be studied frame by frame through the cardiac cycle to detect and quantify bubble signals appearing in the left atrium. Such signals should appear quickly when passing through the interatrial septum. Bubbles appearing in the left atrium easily and spontaneously suggest a ready flow of blood through the defect whereas the need for provocation manoeuvres to get bubbles to appear suggest a lesser flow rate. Various bubble scoring systems have been developed, some of which were originally designed for the assessment of divers with decompression illness, but to date bubble echocardiography cannot be used to measure reliably the size of a foramen ovale or the rate of blood flow through it. Bubbles appearing later than 5 cardiac cycles after right heart opacification are more likely to have passed through an arteriovenous malformation in the peripheral pulmonary circulation. These are usually of little clinical relevance but are prominent in conditions such as hereditary haemorrhagic telangiectasia and may be associated with pulmonary hypertension.
Future developments – small bubbles
The other type of bubble contrast involves very much smaller bubbles requiring suspension in emulsion and these are small enough to pass through the pulmonary circulation and can be used to opacify the left heart. This is particularly useful when determining left ventricular regional wall motion and also in the detection of intracardiac thrombus. These agents also enter the myocardium and there is considerable interest in developing myocardial perfusion imaging using high energy ultrasound pulses to destroy the bubble contrast and subsequently measuring the delay to reopacification which is dependent on local blood flow. This technique remains a research tool and has not yet received widespread clinical or regulatory approval.
This type of contrast agent is relatively expensive but offers impressive intracardiac contrast and opacification provided the imaging technique is modified. Image settings require adjustment, and in particular the power of ultrasound used requires to be reduced to avoid bubble destruction. The mechanical index usually requires to be lowered to 0·3 (compared with 1·0 for routine scans). This may result in a loss of tissue detail but the main reason for using this type of contrast is to determine left ventricular cavity shape and movement. The use of such agents is increasing, particularly in centres performing stress echocardiography where good endocardial definition is essential when assessing regional wall motion and contractility.
In summary, transthoracic echocardiography with second harmonic imaging should now be regarded as the best initial investigation for a patent foramen ovale in patients with suspected paradoxical intracardiac embolism. This offers useful structural cardiac information together with appropriately sensitive and specific detection of the patent foramen ovale.
References
- Daniels C, Weytjens C, Cosyns B et al. Second harmonic transthoracic echocardiography: the new reference screening method for the detection of patent foramen ovale. Eur J Echocardiography 2004; 5(6):449–52.
- Kuhl H, Hoffman R, Merx M et al. Transthoracic echocardiography using second harmonic imaging: diagnostic alternative to transesophageal echocardiography for the detection of atrial right to left shunts in patients with cerebral embolic events. J Am Coll Cardiol 1999; 34:1823–30.
- Hagen P, Scholz D, Edwards W. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc 1984; 59:17–20.
- Pfleger S, Konstantin Haase K, Stark S et al. Haemodynamic quantification of different provocation manoeuvres by simultaneous measurement of right and left atrial pressure: implications for the echocardiographic detection of persistent foramen ovale. Eur J Echocardiography 2001; 2:88–93.