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Alcohol septal ablation (ASA) in hypertrophic obstructive cardiomyopathy reduces left ventricular outflow tract gradients. A third of patients do not respond; inaccurate localisation of the iatrogenic infarct can be responsible. Transthoracic echocardiography (TTE) using myocardial contrast can be difficult in the laboratory environment. Intra-cardiac echocardiography (ICE) provides high-quality images. We aimed to assess ICE against TTE in ASA. The ability of ICE and TTE to assess three key domains (mitral valve (MV) anatomy and systolic anterior motion, visualisation of target septum, adjacent structures) was evaluated in 20 consecutive patients undergoing ASA. Two independent experts scored paired TTE and ICE images off line for each domain in both groups. The ability to see myocardial contrast following septal arterial injection was also assessed by the cardiologist performing ASA. In patients undergoing ASA, ICE was superior in viewing MV anatomy (P=0.02). TTE was superior in assessing adjacent structures (P=0.002). There was no difference in assessing target septum. Myocardial contrast: ICE did not clearly identify the area of contrast in 17/19 patients due to dense acoustic shadowing (8/19) and inadequate opacification of the myocardium (6/19). ICE only clearly localised contrast in 2/19 cases. ICE does not visualise myocardial contrast well and therefore cannot be used to guide ASA. TTE was substantially better at viewing myocardial contrast. There was no significant difference between ICE and TTE in the overall ability to comment on cardiac anatomy relevant to ASA.