Takotsubo syndrome and vaccines: a systematic review.

AIMS: Takotsubo syndrome (TTS) is a rare complication of vaccination. In this study, we sought to provide insight into the characteristics of reported TTS induced by vaccination. METHODS AND RESULTS: We did a systematic review, searching PubMed, Embase, Web of Science, Ovid MEDLINE, Journals@Ovid, and Scopus databases up to 26 April 2023 to identify case reports or case series of vaccine-induced TTS. We then extracted and summarized the data from these reports. Eighteen reports were identified, with a total of 19 patients with TTS associated with vaccinations. Of the 19 included patients, the majority were female (n = 13, 68.4%) with a mean age of 56.6 ± 21.9 years. Seventeen patients developed TTS after coronavirus disease 2019 vaccination, 14 of whom received an mRNA vaccination. Two cases of TTS occurred after influenza vaccination. Among the 19 patients, 17 (89.5%) completed transthoracic echocardiography and 16 (84.2%) underwent angiography procedures. Seven patients (36.8%) completed cardiac magnetic resonance imaging. The median time to symptom onset was 2 (inter-quartile range, 1-4) days. The most common symptoms were chest pain (68.4%), dyspnoea (57.9%), and digestive symptoms (31.6%). A total of 57.9% of patients developed nonspecific symptoms such as fatigue, myalgia, diaphoresis, and fever. Among the 16 reported cases of TTS, 15 patients (93.8%) exhibited elevated cardiac troponin levels, while among the nine reported cases, eight patients (88.9%) had elevated natriuretic peptide levels. All patients had electrocardiographic changes: ST-segment change (47.1%), T-wave inversion (58.8%), and prolonged corrected QT interval (35.3%). The most common TTS type was apical ballooning (88.2%). Treatment during hospitalization typically included beta-blockers (44.4%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (33.3%), and diuretics (22.2%). After treatment, 81.3% of patients were discharged with improved symptoms. Among this group, nine patients (56.3%) were reported to have recovered ventricular wall motion during follow-up. Two patients (12.5%) died following vaccination without resuscitation attempts. CONCLUSIONS: TTS is a rare but potentially life-threatening complication of vaccination. Typical TTS symptoms such as chest pain and dyspnoea should be considered alarming symptoms, though nonspecific symptoms are common. The risks of such rare adverse events should be balanced against the risks of infection.

Design, Synthesis, and Biological Evaluation of the Third Generation 17-Cyclopropylmethyl-3,14ß-dihydroxy-4,5α-epoxy-6ß-[(4'-pyridyl)carboxamido]morphinan (NAP) Derivatives as µ/κ Opioid Receptor Dual Selective Ligands.

µ opioid receptor (MOR) agonists have been widely applied for treating moderate to severe pain. However, numerous adverse effects have been associated with their application, including opioid-induced constipation (OIC), respiratory depression, and addiction. On the basis of previous work in our laboratory, NAP, a 6ß- N-4'-pyridyl substituted naltrexamine derivative, was identified as a peripheral MOR antagonist that may be used to treat OIC. To further explore its structure-activity relationship, a new series of NAP derivatives were designed, synthesized, and biologically evaluated. Among these derivatives, NFP and NYP significantly antagonized the antinociception effect of morphine. Whereas NAP acted mainly peripherally, its derivatives NFP and NYP actually can act centrally. Furthermore, NFP produced significantly lesser withdrawal symptoms than naloxone at similar doses. These results suggest that NFP has the potential to be a lead compound to treat opioid abuse and addiction.