Sacubitril/valsartan decreases mortality in the rat model of the isoprenaline‐induced takotsubo‐like syndrome

Abstract

Aims Takotsubo syndrome (TTS) is an acute potentially reversible cardiac syndrome characterized by variable regional myocardial akinesia that cannot be attributed to a culprit coronary artery occlusion. TTS is an important differential diagnosis of acute heart failure where brain natriuretic peptides are elevated. Sacubitril/valsartan is a novel and effective pharmacological agent for the treatment of patients with heart failure. Our aim was to explore whether treatment with sacubitril/valsartan could prevent isoprenaline-induced takotsubo-like phenotype in rats. Methods and results A total number of 186 Sprague-Dawley male rats were randomized to receive pretreatment with water (CONTROL, n = 62), valsartan (VAL, n = 62), or sacubitril/valsartan (SAC/VAL, n = 62) before receiving isoprenaline for induction of TTS. We recorded heart rate and blood pressure invasively. Cardiac morphology and function were evaluated by high-resolution echocardiography 90 min after the administration of isoprenaline. We documented the survival rate at the time of echocardiography. Compared with the CONTROL group, the SAC/VAL group had less pronounced TTS-like cardiac dysfunction and lower mortality rate, while the VAL group did not differ. Heart rate and blood pressure were not significantly different between the groups. Analysis of cardiac lipids was performed with mass spectrometry. The VAL and SAC/VAL groups had significantly higher levels of lysophosphatidylcholine (LPC), in particular LPC 18:1 and LPC 16:0. Conclusions Pretreatment with sacubitril/valsartan but not with valsartan reduces mortality and attenuates isoprenalineinduced apical akinesia in the TTS-like model in rats. Sacubitril/valsartan could be a potential treatment option in patients with TTS in humans.

Acute stress induces long-term metabolic, functional, and structural remodeling of the heart

“…Tsikas et al suggested that GAA, a non-protein guanidino amino acid acting as analogue of Lys, could induce drastic changes in the heart and kidneys compensating energy requirements in case of insufficient creatine supply 51 . According to Anwar et al, Entresto®, an approved drug that prevents natriuretic peptide degradation, increases BNP levels, and decreases mortality in heart failure patients with reduced EF, decreased cardiac sympathetic activity, attenuated ISO-induced myocardial hypoperfusion, decreasing mortality 52 . On the other hand, a study by Ellison et al focusing on the effects of β-adrenergic overload on cardiomyocytes and cardiac stem cells (CSCs), proposed that CSC activation observed at 3 and 6 d post-ISO contributed significantly to the rapid clinical recovery of the TTC heart 53 .…”

Takotsubo syndrome: unravelling the enigma of the broken heart syndrome?—a narrative review

“…Further investigation and validation are necessary to determine the significance of these findings, considering the low recurrence rate and conflicting results observed in other studies ( 160 , 161 ). It is important to emphasize that there is a lack of evidence regarding other widely used treatments for heart failure, such as sodium-glucose co-transporter 2 inhibitors or angiotensin receptor neprilysin inhibitors, which could potentially have a prognostic impact on patients with TTS ( 162 ). Additionally, for patients experiencing multiple, recurrent episodes of TTS triggered by emotional stressors or those with neuropsychiatric disorders, targeting the psychological response to emotionally stressful triggers may be a potential therapeutic approach ( 163 ).…”

“…Interestingly, a variable TTS pattern upon recurrence is observed in up to 20% of cases ( 8 ). However, there are conflicting results regarding potential predictors of TTS recurrence ( 162 , 172 ). Unfortunately, we lack evidence about the optimal treatment to prevent such recurrences.…”