The Broken Heart Study II (BHS-II) (BHS)

Heterogeneity and Predictors of Stress Reactivity in Takotsubo Syndrome

The goals of this study are as follows:

1. To rigorously establish and characterize heterogeneity in the pathophysiology of Takotsubo Syndrome (TS).
2. To rigorously test the contribution of TS triggering events and mental stress responsiveness to 1-year prognosis after TS event.

Study Overview

• Status: Recruiting
• Conditions: Takotsubo Cardiomyopathy
• Intervention / Treatment: Other: Stress reactivity test

Detailed Description

Newly admitted patients with a validated diagnosis of Takotsubo Syndrome (TS; n=106) will be enrolled from 3 large medical centers in the Providence, Rhode Island area. Between 2 and 4 weeks after discharge, clinically stable patients will undergo an in-person comprehensive interview to identify the events proximal to the onset of TS symptoms, complete a battery of psychosocial questionnaires and undergo a validated laboratory stress protocol. Baseline and reactive changes in measures of autonomic nervous system activity (epinephrine and norepinephrine - primary outcome), and in the secondary outcomes of cardiac vagal control and left ventricular function (ejection fraction; regional and global longitudinal strain assessed with speckle tracking echocardiography) will be assessed. Echocardiographic evaluations will be repeated 12 months thereafter together with information on major adverse cerebrovascular events.

• Study Type: Interventional
• Enrollment (Anticipated): 106
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elena Salmoirago-Blotcher, MD, PhD; Phone Number: 38325 401-793-8325; Email: Elena_Salmoirago-Blotcher@brown.edu

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • Recruiting
      • The Miriam Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >=18
• A new diagnosis of takotsubo syndrome fulfilling Mayo Clinic criteria
• Ability to understand and speak English

Exclusion Criteria:

• Inability or unwillingness to give informed consent
• Severe cognitive impairment
• Uncontrolled hypertension
• Acute psychosis
• High suicidal risk
• Pregnancy
• Poor echocardiographic window
• Conditions that would interfere with adherence to study requirements (e.g., ongoing alcohol or substance abuse)
• If the participant is clinically unstable

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Stress reactivity; Stress reactivity test

Other: Stress reactivity test; The protocol consists of Resting Baseline (BL), Emotion Recall (ER), followed by a Recovery Phase (RP). Heart rate and blood pressure are measured at baseline and then every 5 minutes during ER and RP. Resting Baseline (BL - 10 min). The participant is instructed to rest quietly. Emotion Recall (ER - 5-10 min). The participant is instructed to think about the incident associated with the onset of their cardiac event and bring to mind details of the incident. When the participants have the incident clearly in mind, they are instructed to relate the incident and their experience out loud; frequent questions to re-elicit the emotion are asked. Recovery Phase (RP - 20 min). Upon completion of RP, the catheter is removed and participants are de-instrumented. Blood samples for plasma catecholamines, assessments of heart rate variability, and echocardiograms are performed 10-min into BL, 10-min into ER, and 18 minutes into RP.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change (in pg/mL) in plasma epinephrine levels	Blood samples for plasma epinephrine are collected 10-min into Baseline, 10-min into Emotion Recall, and 18 minutes into Recovery Phase. Change will be calculated by subtracting Baseline epinephrine levels from Emotion Recall levels.	Up to 4 weeks
Mean change (in pg/mL) in plasma norepinephrine levels	Blood samples for plasma norepinephrine are collected 10-min into Baseline, 10-min into Emotion Recall, and 18 minutes into Recovery Phase. Change will be calculated by subtracting Baseline epinephrine levels from Emotion Recall norepinephrine levels.	Up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in high frequency power heart rate variability (hf-HRV) in Ln msec (square)	High frequency power heart rate variability (hf-HRV) will be determined by averaging high frequency values for 4-min segments within each phase (Baseline, Emotion Recall), and change will be calculated (Emotion Recall minus Baseline). Data will be collected using a Digital Holter ECG Recorder - 5 Lead, 2 Channel.	Up to 4 weeks
Left ventricular ejection fraction (%)	A trans-thoracic echocardiogram will be performed with computation of ejection fraction according to current guidelines.	12 months
Average Global Longitudinal Strain (GLS)	Global Longitudinal Strain (GLS) will be assessed using off-line analysis software (TomTec imaging systems). GLS will be calculated as the average left ventricular longitudinal strain across the segments obtained using apical two, three, and four-chamber views. Because myocardial contraction results in left ventricular shortening in systole, GLS is a negative value.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with major adverse cardiac and cerebrovascular events	Composite of death from any cause, recurrence of TS, stroke, transient ischemic attack, and myocardial infarction.	12 months

Collaborators and Investigators

• Sponsor: The Miriam Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2020
• Primary Completion (Anticipated): November 30, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: March 26, 2020
• First Posted (Actual): March 27, 2020

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 13, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction, Left; Ventricular Dysfunction; Cardiomyopathies; Takotsubo Cardiomyopathy
• Other Study ID Numbers: R01HL149672 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data generated under the project will be shared as per National Institutes of Health (NIH) Grant Policy and Lifespan Institutional Review Board guidelines. De-identified research data will be made available in a timely manner once the main findings from the final research data set have been accepted for publication. Access to these data will be available for educational or research purposes. Data will be de-identified to avoid linkages to individual research participants and will be free of variables that could lead to deductive disclosure of the identity of individual subjects.
• IPD Sharing Time Frame: De-identified research data will be made available once the main findings from the final research data set have been accepted for publication.
• IPD Sharing Access Criteria: Researchers interested in obtaining the de-identified data and associated documentation (e.g. codebook) can make a request to the principal investigator. requestors will be asked to sign a data sharing agreement that includes conditions to 1) protect the identity of participants, 2) limit use of data for educational and research purposes, and 3) prevent transfer of data to other users, and 4) acknowledge the data source. The de-identified data will be shared using Excel or Statistical Package for the Social Sciences (SPSS) file formats.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No