# Heterogeneity and predictors of stress reactivity in takotsubo syndrome

> **NIH NIH R01** · MIRIAM HOSPITAL · 2022 · $555,963

## Abstract

PROJECT SUMMARY/ABSTRACT
Takotsubo syndrome (TS) is an increasingly recognized condition characterized by acute, reversible systolic
heart failure which uniquely affects older women (more than 90% of cases). Although most patients recover
after an acute episode, survivors have a high risk of long-term major cerebrovascular events (MACCE) and of
chronic impairments of the left ventricular (LV) function. Despite its clinical relevance, important knowledge
gaps exist about this interesting and perhaps underappreciated condition. While there is a general consensus
that an exaggerated sympathetic nervous system (SNS) discharge is the final common pathophysiologic event
that underlies the onset of acute systolic heart failure in TS, this condition has considerable heterogeneity.
First, exposure to an emotional trigger was thought to be a defining precipitant of TS, but recent registry data
indicate instead that emotional triggers are present only in 1/3 of cases, with physical triggers (1/3) and no
triggers (1/3) accounting for the remaining cases. Second, the pathophysiological pathway linking the
precipitating trigger to the onset of TS remains to be articulated. Third, it is unclear why certain individuals
develop an exaggerated SNS response when exposed to emotional triggers which sooner or later affect all
individuals throughout the lifespan with no or limited health consequences. Finally, no study has rigorously
tested the contribution of triggering event and mental stress responsiveness to the long-term prognosis of
these patients. To address these key evidence gaps we will conduct a mechanistic clinical trial among 246
newly admitted patients with a validated diagnosis of TS from 3 large medical centers in the Providence, RI
area. Participants will undergo a comprehensive interview to identify the events proximal to the onset of TS
and complete a battery of psychosocial questionnaires 2 weeks after hospital discharge. Approximately 4
weeks after discharge they will undergo a laboratory mental stress protocol previously utilized by our group.
Baseline and reactive changes in measures of autonomic nervous system activity (circulating catecholamines
and cardiac vagal control), LV function (2D speckle tracking echocardiography (2D-STE)), and hemodynamic
parameters will be assessed. LV function and MACCE will be assessed 12 months later. The proposed study
will address the noted evidence gaps by a) Rigorously assessing the full range of circumstances proximal to
TS onset, b) Assessing the constellation of physiological elements that define TS (autonomic nervous system
activity and LV function) under controlled conditions, and c) Link the type of trigger to physiology. Furthermore,
by using 2D-STE we will be able to capture both reactive and long-term subtle anomalies of LV function in
these patients. This will be the first study to rigorously investigate the heterogeneity in clinical presentation,
physiopathology, and prognosis in TS. The identifica...

## Key facts

- **NIH application ID:** 10348715
- **Project number:** 5R01HL149672-03
- **Recipient organization:** MIRIAM HOSPITAL
- **Principal Investigator:** Elena Salmoirago-Blotcher
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $555,963
- **Award type:** 5
- **Project period:** 2020-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10348715

## Citation

> US National Institutes of Health, RePORTER application 10348715, Heterogeneity and predictors of stress reactivity in takotsubo syndrome (5R01HL149672-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10348715. Licensed CC0.

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