A Subtle Sign of Something Sinister

The ECG shows:

• Sinus rhythm at 54 bpm
• Normal axis
• Normal intervals
• Borderline left atrial enlargement with a bifid P wave in lead II (P mitrale) and enlargement of the terminal negative portion of the P wave in V1
• Essentially normal ST segments and T waves, except for some non-specific T-wave flattening in aVL
• Inverted U waves in the lateral leads I, V5 and V6 (and possibly also in leads II and III)

Most important finding: inverted U waves in the lateral leads

In patients presenting with chest pain, inverted U waves:

• Are a very specific sign of myocardial ischaemia
• May be the earliest marker of unstable angina and evolving myocardial infarction
• May be observed during attacks of Prinzmetal angina
• Have been associated with  LAD or LMCA occlusion and the presence of left ventricular dysfunction
• U wave inversion tends to occur mainly in the lateral leads (I, aVL, V5-6) and may be seen either during ischaemic symptoms or at rest.

With this patient’s history, the U wave inversion would be strongly suggestive of an acute coronary syndrome (unstable angina or NSTEMI).

Inverted U waves may also be seen in:

• Hypertension
• Valvular heart disease
• Congenital heart disease
• Cardiomyopathy
• Hyperthyroidism

• This patient needs to be managed as a suspected acute coronary syndrome with analgesia, nitrates, aspirin, clopidogrel +/- low-molecular-weight heparin (enoxaparin)
• At this stage there are no indications for thrombolysis or emergent PCI
• He will need serial ECGs and troponins to look for evidence of infarction
• He needs to be admitted under a cardiology team to a monitored bed for further investigation (e.g. angiography

• This was a difficult case to sell to cardiology, as the initial troponin I was equivocal (0.05 ng/mL at 2 hours) and the cardiology registrar was dubious about the significance of the ECG changes
• The patient ended up spending the night in ED in a monitored bed
• Serial cardiac enzymes confirmed a NSTEMI, with a troponin I of 0.87 ng/mL at 6 hours and 4.0 ng/mL at 12 hours
• Serial ECGs remained unchanged throughout his hospital stay – the lateral U wave inversion persisted and there was no progression to ST segment elevation or depression
• In the morning, he was transferred to a CCU bed under the care of a cardiologist, with angiography planned for the following day

• Gerson MC, McHenry PL. Resting U wave inversion as a marker of stenosis of the left anterior descending coronary artery. Am J Med. 1980 Oct;69(4):545-50.
• Girish MP, Gupta MD, Mukhopadhyay S, Yusuf J, Sunil Roy TN, Trehan V. U wave: an important noninvasive electrocardiographic diagnostic marker. Indian Pacing Electrophysiol J. 2005 Jan 1;5(1):63-5.
• Pérez Riera AR, Ferreira C, Filho CF, Ferreira M, Meneghini A, Uchida AH, Schapachnik E, Dubner S, Zhang L. The enigmatic sixth wave of the electrocardiogram: the U wave. Cardiol J. 2008;15(5):408-21.
• Sovari AA, Farokhi F, Kocheril AG. Inverted U wave, a specific electrocardiographic sign of cardiac ischemia. Am J Emerg Med. 2007 Feb;25(2):235-7.
• Nagayoshi et al. Inverted U-wave and myocardial ischaemia. QJM: An International Journal of Medicine, Issue 7, July 2018, Page 493.