# Takotsubo Syndrome: The First Non-Acute Proteomic Analysis by Remote Dried Blood Microsampling

## TL;DR

This study is the first to analyze non-acute blood proteins in Takotsubo syndrome patients, revealing potential long-term biological changes linked to the condition.

## Contribution

The first non-acute proteomic analysis of Takotsubo syndrome using remote dried blood microsampling.

## Key findings

- Agnostic clustering distinguished TTS patients from controls based on proteomic profiles.
- Differentially regulated proteins were enriched in complement activation, nitric oxide signaling, and antioxidant pathways.
- Findings suggest persistent cardiomyopathy or predisposition mechanisms in non-acute TTS.

## Abstract

Takotsubo syndrome (TTS) is an under-recognized form of acute-onset heart failure typically precipitated by stress. While recovery of cardiac function is described over the course of weeks, adverse outcomes after apparent recovery are increasingly recognized. However, the pathophysiology of non-acute manifestations remains poorly understood. We used mass-spectrometry-based discovery proteomics from remotely collected non-acute dried blood microsamples to perform a case-control study in 62 participants with a prior TTS episode (median of 2.24 years prior to sample collection) and 47 reference controls. We quantified 398 unique proteins, and found that agnostic clustering techniques showed separation between TTS and reference control samples. This represents the first proteomic characterization of non-acute TTS. Pathway analysis of the 52 differentially regulated proteins demonstrated enrichment of proteins involved in complement activation, nitric oxide signaling, and with antioxidant activity. These enriched pathways may be suggestive of a persistent cardiomyopathy resulting from or predisposing to TTS.

The online version contains supplementary material available at 10.1007/s12265-026-10752-0.