Takotsubo syndrome (TTS) is a stress-induced condition characterized by a state of catecholamine toxicity leading to a specific form of transient myocardial dysfunction (Chanda et al. 2025; Finsterer et al. 2014; Yalta et al. 2024). To date, TTS evolution has been very rarely reported in patients with myotonic dystrophy type 1 (DM1) and has been mostly attributed to a variety of neurogenic mechanisms including autonomic dysfunction and co-existing stressful triggers (respiratory insufficiency, etc.) in these patients (Chanda et al. 2025; Finsterer et al. 2014). We read with great interest the recent case series by Chanda et al. (2025) particularly elaborating on the pathogenesis of TTS evolution in the setting of DM1. In this setting, we would like to make a few comments and suggest an alternative mechanism of TTS evolution (and its potential implications):

First, TTS episodes in patients with DM1 may potentially emerge as a consequence of mechanical factors including sudden increases in intraventricular gradient. In general, these mechanically triggered TTS episodes have been attributed to sudden left ventricular outflow tract or midventricular obstruction (LVOTO or MVO) leading to afterload mismatch and supply–demand ischemia along with consequent myocardial stunning involving the apex (resulting in characteristic apical ballooning pattern) (Citro et al. 2023; Madias 2024; Yalta et al. 2024, 2020). Notably, this form of TTS episodes has been usually encountered in patients with pre-existing myocardial conditions including hypertensive heart disease and hypertrophic cardiomyopathy (HCM) usually presenting with mild or borderline hypertrophy that might usually go undetected on initial evaluation (Citro et al. 2023; Madias 2024; Yalta et al. 2024, 2020).

Similarly, DM1 is well known to be associated with significant myocardial changes including hypertrophy, fibrosis, and fatty infiltration along with muscular disarray (Chanda et al. 2025; Mahadevan et al. 2021). Moreover, overt hypertrophic cardiomyopathy accompanied by a LVOTO was also reported previously in a patient with DM (Igarashi et al. 1998). These findings may potentially suggest intraventricular mechanical factors (due to pre-existing myocardial disease) as underlying triggers of TTS and its recurrences in patients with DM1. Endomyocardial biopsy in patient-2 revealed fatty infiltrates suggesting myocardial involvement due to DM1. We wonder whether they also performed genetic analysis for co-existing congenital conditions including HCM in these patients.

Second, intraventricular gradient due to myocardial disease has potential diagnostic implications as well. Accordingly, this gradient may not be significant (or even absent) on admission with a TTS episode, yet may be easily provoked with certain maneuvers (maneuvers reducing cardiac preload and/or afterload) (Yalta et al. 2024). Both the index and recurrent TTS episodes in patient-1 reportedly emerged after bouts of nausea and vomiting that might have induced a significant and transient intraventricular gradient (and subsequent TTS episode) through a Valsalva mechanism (Yalta et al. 2024). Moreover, adrenergic discharge due to various stressors, besides its direct impact on the myocardium, may also provoke an intraventricular gradient mostly through induction of myocardial contractility in patients with pre-existing myocardial disease (Citro et al. 2023; Madias 2024). In patient-2, myocardial changes in the basal anteroseptum (on cardiac magnetic resonance imaging (MRI)) might be associated with an emotionally triggered transient LVOTO ultimately leading to TTS with an apical ballooning pattern.

Of note, challenge tests including dobutamine (or exercise stress) echocardiogram generally provoke a significant intraventricular gradient in patients with a subtle intraventricular gradient and may have diagnostic value (Citro et al. 2023; Yalta et al. 2024). We recommend the use of challenge tests for the diagnostic confirmation of mechanically triggered TTS episodes in both patients. However, challenge tests should be performed following the complete recovery of apical ballooning and stabilization of clinical features in this context (Yalta et al. 2024).

Finally, confirmation of intraventricular gradient as a potential TTS mechanism may have therapeutic implications and may warrant the use of pharmacological (beta blockers, disopyramide in the absence of conduction disorders) and non-pharmacological (septal ablation, etc.) preventive strategies against intraventricular gradient (for the prevention of future TTS recurrences) (Citro et al. 2023; Yalta et al. 2024).

In conclusion, sudden intraventricular obstruction (usually in a transient manner) due to pre-existing myocardial disease may be regarded as an alternative theory in TTS pathogenesis in patients with DM1. Importantly, timely diagnosis and proper management of significant intraventricular gradient (at rest or provoked) may significantly improve cardiovascular outcomes in patients with DM1.

Conflicts of Interest

The authors declare no conflicts of interest.