Apical hypertrophic cardiomyopathy (ApHCM) is complex phenotypic variant of the classical hypertrophic cardiomyopathy [1]. It can be asymptomatic or present with dyspnea, chest pain, syncope as well as severe diastolic dysfunction even sudden cardiac death [2‐4]. Given its diverse presentation forms, clinical evaluation alone cannot be relied upon. Understanding the unique electrocardiogram (ECG) features of ApHCM can be of assistance in the diagnostic process of this uncommon disease.

Because of similar clinical manifestations and large negative T (neg T) waves in precordial leads on ECG, most previous case reports misdiagnosed ApHCM as non-ST elevation acute coronary syndrome (NSTEACS) [5‐11]. Differentiation of these two diseases can be challenging, but has an important role in the selection of an appropriate treatment strategy. The 12-lead ECG is the simplest and widely used clinical diagnostic test. Several ECG features of ApHCM have been reported which may help to make these distinctions [12, 13]. These include higher T wave voltage and peak voltage, T wave asymmetry and higher R waves. Nevertheless, previous studies were restricted to case reports or a small group of patients, the serial ECG differences between ApHCM and NSTEACS have not been sufficiently elucidated.

Our aim was to explore the ECG patterns in ApHCM patients and compare them with NSTEACS patients to distinguish between the two diagnoses, thereby helping choose a more appropriate treatment strategy and finally improving clinical outcome.

The current study revealed that the peak voltage of neg T and giant R clearly differed between ApHCM and NSTEACS, which occurred most frequently in leads V2-V6. We also showed that degree of ST-segment depression differed, particularly in leads V3-V6, between the two diseases. To our best knowledge, this is the first study to examine the change of ST-segment in patients with ApHCM and NSTEACS.

ApHCM has been recognized as Japanese-variant of hypertrophic cardiomyopathy since its high prevalence in the Japanese population [20, 21]. The etiology of ApHCM is multifactorial, with studies suggesting variants with a genetic predisposition and exclusive development during adulthood [22, 23]. ApHCM presents some particular electrocardiographic findings including deep inversion of the T waves (giant T waves) and the increase of the QRS complex voltage in the precordial leads [13]. However, in clinical setting, the ApHCM patients with giant neg T waves recorded in the ECG were always suspected of having acute coronary syndrome (ACS) [24]. Rogers reported a 61-year-old man admitted with chest pain, his ECG showed a biphasic T wave in lead V2, neg T waves in leads II and aVL, deep symmetrical T-wave inversions and ST depressions in leads V3–V6 [11]. He was suspected of ACS undergoing an emergent cardiac catheterization which revealed no coronary artery disease but a “spade like” pattern suggestive of ApHCM. Meghrajani reported a 66-year-old woman whose initial ECG showed T wave inversions in the lateral leads was diagnosed with type 2 myocardial infarction [25]. Coronary angiogram as well as cardiac left ventriculogram showed apical hypertrophy without coronary artery occlusion. From the ECG point of view, especially inverted T waves in V3-V6, ApHCM is often difficult to differentiate from NSTEACS. Previous studies had been confined to case reports or a relatively small number of patients. Herein we conducted an observational and retrospective study, the ECG findings could be conducive to differentiate ApHCM and NSTEACS early thus preclude the need for urgent coronary angiography and make accurate diagnosis and treatment essential for improved outcome.

To our knowledge, only the study reported by CHILLIK scrutinized ECG differences between ApHCM and NSTEMI [12]. They compared ECG changes between 19 patients with ApHCM and 19 patients with NSTEMI. They assessed neg T waves in leads V1-V6 showing a greater T-wave asymmetry. However, their study included only a small number of patients and they did not examine differences in ST-segment and the distributions or numbers of leads with neg T waves. Moreover, most previous studies showed T-wave typically displays > 10 mm inversions within the anterolateral leads in ApHCM, most prominent in V4 and V5 yet limb leads were received little attention. We therefore evaluated the R and T waves in all 12 leads. We identified the patients with ApHCM presented higher R and T wave voltage and peak voltage, similar to previous published studies. Besides, our study showed that ApHCM was associated with a greater ST-segment depression compared with NSTEACS. Meanwhile, the number of leads with neg T wave across 12-leads was more in patients with ApHCM. Giant neg T wave was exclusively found in ApHCM and the sum of R wave in lead V5, neg T wave in lead V6 and depressive (dep) ST-segment in lead V4 > 2.585 mV had the highest predictive value for ApHCM. Interestingly, we found on precordial leads of ApHCM, the amplitude of T-wave inversion displayed TV4 > TV5 > TV3, on the other hand, the amplitude of R-wave showed RV5 > RV4 > RV3. A series of new discoveries in our study would further facilitate differential diagnosis between ApHCM and NSTEACS.

The mechanisms responsible for the ECG differences and the underlying electrophysiologic conditions between ApHCM and NSTEACS are uncertain. These voltage criteria of ApHCM may be related to both LV hypertrophy and differences in localized wall thickness leading to disparities in the duration of repolarization. ApHCM is characterized by circular LV hypertrophy, while in NSTEACS, LV hypertrophy presented at the opposite side of the myocardium because of cardiac remodeling, thus it is not a circular hypertrophy [26]. In ApHCM, the mechanism for enormous R waves, dramatically in V3–V4 leads, is due to the apical distribution of hypertrophy opposite to the non-muscular elements of the fibrous cardiac skeleton of the mitral valve and annular plane. This result in an unopposed depolarization vectorial depolarization forces directed towards the cardiac apex [27]. Additionally, an alternative mechanism for prominent R waves is increased resistivity of cardiac muscle caused by fibrosis and myofibril disarray in the hypertrophied regions. Contrary to prominent R-waves, giant neg T waves isattributed to opposite vectorial orientation away from the cardiac apex. Neg T wave and dep ST-segment is considered a secondary phenomenon to high R-wave [26, 27].

Finally, it is important to apply these ECG rules into clinical context. Patient history is essential as ApHCM is a condition with varying clinical presentations. Active chest pain may suggest NSTEACS, whereas dyspnea usually imply ApHCM. In NSTEACS, you can find reciprocal ST changes or “mirror changes” on ECG, which is not usual in ApHCM [28]. Besides, ECG changes in ApHCM are generally stable against the rapid changes in ST-segment and T wave seen in serial ECGs of NSTEACS patients.

Compared with NSTEACS, ApHCM patients presented higher voltage of R and neg T wave as well as greater ST-segment depression in the 12-lead ECG. Our proposed ECG characteristics can help to differentiate ApHCM from NSTEACS in clinical setting. Further studies in greater numbers of subjects are needed to verify our results.