Proteomic analysis identified 52 proteins significantly differentially regulated in women with prior Takotsubo syndrome (median 2.24 years post-event) compared to reference controls, including enrichment in complement activation, nitric oxide biosynthesis, and antioxidant activity pathways.
Observational (n=109)
Yes
Does a prior episode of Takotsubo syndrome result in a distinct non-acute blood proteomic signature compared to matched controls?
Non-acute Takotsubo syndrome is associated with a distinct blood proteomic signature involving complement activation and nitric oxide signaling, suggesting persistent biological abnormalities long after the acute event.
Effect estimate: 52 proteins differentially regulated (absolute log2 fold change >0.6 and FDR-adjusted p<0.05)
p-value: p=<0.05 for 52 proteins; pathway enrichment p-values down to 4.38x10^-7
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. Graphical Abstract
Marano et al. (Fri,) conducted a observational in Women with prior Takotsubo syndrome (median 2.24 years since event) compared to age-, sex-, and race-matched reference controls (n=109). Proteomic analysis identified 52 proteins significantly differentially regulated in women with prior Takotsubo syndrome (median 2.24 years post-event) compared to reference controls, including enrichment in complement activation, nitric oxide biosynthesis, and antioxidant activity pathways.