Echocardiography in cryptogenic stroke patients
Cryptogenic strokes are brain infarcts that occur without a clear mechanism. The proportion of patients who are classified as having had a cryptogenic stroke is dependant on the criteria used for describing stroke aetiology (e.g. TOAST vs ASCO), the age of the population described and the extent of investigations undertaken but may account for over 40% of cases.
Echocardiography is an essential tool for the investigation of patients who have suffered a brain infarct. Transthoracic echocardiograpy is necessary in almost all patients with bubble contrast echocardiography and transoesophageal echocardiography (TOE) being reserved for specified populations dependent on local policies and resources.
The purpose of echocardiography is to identify sources of cardiac/aortic embolisation that may be considered as definitive or non-definitive (major or minor risk) as per recognised diagnostic criteria.
The following would be considered definitive sources:
- Intra-cardiac mass
- Myxoma (or other tumour)
- Vegitation/Infective endocarditis
- Aortic arch atheroma (plaques of 4mm or more)
The following would be considered non-definitive but major risk sources:
- Prosthetic heart valves (left sided)
- Mitral stenosis
- Dilated cardiomyopathy (Ejection Fraction [EF] < 35%)
- Left ventricular aneurysm
- Patent Foramen Ovale (PFO) with in-situ thrombus or concomitant deep vein thrombosis (DVT)/pulmonary embolus (PE)
The following would be considered non-definitive and minor risk sources:
- Left ventricular akinesia (EF > 35%)
- Spontaneous echo contrast
- Patent Foramen Ovale
- Atrial Septal Aneurysm (ASA)
- Atrial Septal Defect (ASD)
- Mitral annular calcification
- Calcific aortic stenosis
- Mitral valve prolapse
Transthoracic Echocardiography (TTE)
Transthoacic Echocardiography is indicated in almost all patients who have suffered a brain infarct. It is widely available and will accurately assess cardiac chamber and valvular structure and function in the majority of individuals. Although not as sensitive as transoesophageal echocardiography it will, in a proportion, be able to identify potential cardiac sources of embolisation without the need for other more specialist techniques. Pathologies that can be readily identified using TTE include left ventricular thrombus (video 1), left atrial myxoma (videos 2 & 3) and large left sided vegetations (videos 4 & 5).
|Video 1||Video 2|
|Video 3||Video 4|
Bubble contrast Echocardiography
Bubble contrast echocardiography is undertaken to investigate whether a patient has a right to left shunt. It is usually reserved for "young" patients with cryptogenic strokes (a relative term but frequently defined as those under the age of 55 years) in which population there is a significantly increased incidence of Patent Foramen Ovale (P.F.O.).
Bubble contrast echocardiography can be performed with transthoracic (video 6) or transoesophageal (video 7) echocardiography with pros and cons to both approaches.
A detailed methodological description of how to perform a bubble contrast echocardiogram along with a discussion on the atrial septum in relation to cryptogenic strokes has been published previously by our group.
|Video 6||Video 7|
Transoesophageal Echocardiography (TOE)
TOE is a very sensitive imaging modality that should be performed on all individuals who have suffered a brain infarct, have no definitive cardiovascular source of embolus identified on standard rhythm monitoring and standard cardiac/vascular imaging (including transthoracic echocardiography) AND in whom any identified pathology would likely impact on their future management.
Whilst a complete echocardiographic study in all individuals is desirable the main areas of focus in a patient with a brain infarct are:
- Inter-atrial septum
- Left atrium (LA) and left atrial appendage (LAA)
- Aorta (ascending, arch and descending)
- Mitral valve (MV)
- Aortic valve (AV)
The technicalities of how to image each area are described in many texts including those listed under further reading.
The purpose of imaging the inter-atrial septum is primarily to confirm or refute the presence of a patent foramen ovale, an atrial septal aneurysm or an atial septal defect. When an atrial septal abnormality is identified the echocardiographer should image to the inferior vena cava (IVC)/right atrium (RA) looking for a Eustachion valve or Chiari network as the presence of either is believed to be associated with increased right to left shunting and a greater risk of paradoxical embolisation.
|Video 8||Video 9|
A PFO is diagnosed when there is 2D evidence of incomplete fusion of the septum primum and septum secundum in addition to right to left shunting identified by bubble echocardiography (TTE or TOE). If a PFO is present it is useful to measure the "tunnel separation"; this will suggest the degree of risk associated with the lesion as well as guide potential intervention.
An ASD can be a primum, secundum or sinus venosus type. The most common ASD is a secundum type and is diagnosed when there is 2D evidence of complete septum primum and septum secundum fusion, a defect within the septum primum and color Doppler evidence of left-right shunting. If there is incomplete fusion of the septum primum and septum secundum and a defect within the septum primum the lesion is commonly referred to as a fenestrated PFO as opposed to an ASD. When an ASD is diagnosed then the operator should specifically check that all pulmonary veins drain appropriately into the left atrium as there is an increased incidence of anomolous pulmonary venous drainage.
An ASA is a redundancy of tissue of the septum primum that bulges into the right atrium, left atrium or both. There are a number of different definitions but probably the most recognised echocardiographic diagnostic criteria is a maximal deviation of the septum primum from the plan of the inter-atrial septum of 10mm or more. Atrial septal aneurysms usually occur with PFO and are associated with an 8 fold increase in risk of recurrent stoke 
Left atrium and left atrial appendage
The aim of imaging the left atrium (LA) and its appendage (LAA) is to look for masses; most especially thrombus. Whilst large masses (e.g. myxoma) may be present and identified by transthoracic echocardiography they are rare in crptogenic stroke patients. Still rare (in the absence of atrial fibrillation) but less so are the pathological entities of spontaneous echo contrast (SEC) and small thrombi that are usually confined to the LAA (video 10) and almost always require TOE for their detection.
Atheroma (defined as an irregular intimal thickening of at least 2mm) in the arch/descending aorta is a common finding on TOE examination in the general population aged 45 years or older (video 11). It can be classified into grades I-IV  with grades II-IV being considered as definitive causes of stroke when investigating patients who have suffered a brain infarct. Ascending aortic dissection is a rare but important cause of ischaemic stroke. Neurological symptoms are often associated with other symptoms (e.g. chest/back pain) or signs (e.g. aortic regurgitant murmur)alerting the attendant phtsician to this possible diagnosis. If suspected a TOE, thoracic CT or MRI should be requested immediately.
Mitral and Aortic valves
Abnormalities of the aortic and mitral valves associated with ischaemic strokes include vegitations (videos 12a and 12b) and papillary fibroelastoma (video 13). A vegitation typically appears as an independantly mobile mass with different acoustic properties from the valve and is most frequently found on the upstream side of the valve. Although a vegitation may be detected by TTE the sensitivity of TOE is far greater (90-100%).  In addition to the identification of a vegitation as a cause of ischaemic stroke it is important to assess the risks of recurrence with embolisation of vegitative material being most commonly seen with large (> 10mm; very high rates if > 15mm) vegitations and those attached to the mitral valve. Fibroelastomas are the most common valve-assoiated tumour accounting for upto 90% of them. They are usually pedunculated and attached to the downstream side of the valve with variable degrees of mobility. Differentiating a fibroelastoma from a vegitation is dependant on clinical context as opposed to specific echocardiographic features.
|Video 12a||Video 12b||Video 13|
- ↑ Cotter PE, Belham M, Martin PJ. Stroke in younger patients: The heart of the matter. J Neurol 2010; 257(11):1777-87.
- ↑ Serena J, Marti-Fabregas J, Santamarina E et. al. Recurrent stroke and massive right-to-left shunt: Results from the prospective spanish multicenter (CIDICA) study. Stroke 2008; 39: 3131-6.
- ↑ Cotter PE, Martin PJ, Belham M. Towards understanding the Atrial Septum in Cryptogenic Stroke. International Journal of Stroke 2011; 6(5):445-53.
- ↑ Mas JL, Arquizan C, Lamy C et.al. Recurrent cerebrovascular events associated with patent foramen ovale, atrial septal aneurysm or both. NEJM 2001; 345 (24): 1740-6.
- ↑ Montgomery DH, Ververis JJ, McGorisk G et.al. Natural history of severe atheromatous disease of the thoracic aorta: A transoesophageal study. JACC 1996; 27: 95-101.
- ↑ Evangelista A, Gonzalez-Alujas MT. Echocardiography in infective endocarditis. Heart 2004; 90: 614-7.
- European Association of Echocardiography: Recommendations for echocardiography use in the diagnosis and management of cardiac sources of embolism. European Journal of Echocardiography 2010; 11: 461-76.
- Transesophageal Echocardiography in clinical practice (ISBN 978-1-84882-620-5)