Takotsubo CardiomyopathyBHSNCT04325321
The Broken Heart Study II (BHS-II)
A study testing Stress reactivity test in people with Takotsubo Cardiomyopathy, run by The Miriam Hospital at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Takotsubo Cardiomyopathy
- What is being tested?
- Stress reactivity test
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Sep 2020to 28 Feb 2026
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >=18
- A new diagnosis of takotsubo syndrome fulfilling Mayo Clinic criteria
- Ability to understand and speak English
Who cannot join
- Inability or unwillingness to give informed consent
- Severe cognitive impairment
- Uncontrolled hypertension
- Acute psychosis
- High suicidal risk
- Pregnancy
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Heterogeneity and Predictors of Stress Reactivity in Takotsubo Syndrome
The goals of this study are as follows:
- To rigorously establish and characterize heterogeneity in the pathophysiology of Takotsubo Syndrome (TS).
- To rigorously test the contribution of TS triggering events and mental stress responsiveness to 1-year prognosis after TS event.
Read the 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.
- Conditions
- Takotsubo Cardiomyopathy
- Being tested
- Stress reactivity test
- Medical subject headings
- Takotsubo Cardiomyopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stress reactivity testOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Stress reactivity | Other | Stress reactivity test Receives: Other: Stress reactivity test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change (in pg/mL) in Plasma Epinephrine Levels
Blood samples for plasma epinephrine are collected during the stress reactivity test, 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.
Measured: At baseline
Mean Change (in pg/mL) in Plasma Norepinephrine Levels
Blood samples for plasma norepinephrine are collected during the stress reactivity test, 10-min into Baseline, 10-min into Emotion Recall, and 18 minutes into Recovery. Change will be calculated by subtracting Baseline epinephrine levels from Emotion Recall norepinephrine levels.
Measured: At baseline
Secondary outcomes (2)
Change in High Frequency Power Heart Rate Variability (Hf-HRV) in Ln Msec
High frequency power heart rate variability (hf-HRV) will be determined during the stress reactivity test 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.
Measured: At baseline
Mean Change in Global Longitudinal Strain (GLS)
GLS will be assessed during the stress reactivity test using off-line analysis software (TomTec imaging systems) and 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. Change will be calculated by subtracting Baseline GLS from Emotion Recall GLS.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2020
- Study start2 Sep 2020
- Primary completion11 Nov 2025
- Study completion28 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Takotsubo CardiomyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Miriam Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Elena Salmoirago-Blotcher, The Miriam Hospital
- Investigators
- Elena Salmoirago-Blotcher, MD, PhD, Principal investigator, The Miriam Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04325321
- Sponsor's protocol ID
- R01HL149672
- Other IDs
- R01HL149672
- Acronym
- BHS
- Status last verified
- Sep 2026
- First submitted
- 23 Mar 2020
- Last updated
- 29 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Salmoirago-Blotcher E, Keirns NG, Ouaddi S, Tripolone J, Liu C, Breault C, Dettmer A. Chronic adrenocortical activity and onset of Takotsubo syndrome. Eur J Cardiovasc Nurs. 2026 Jul 28;25(5):1033-1040. doi: 10.1093/eurjcn/zvag023.
PubMed 41562264
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Heterogeneity and Predictors of Stress Reactivity in Takotsubo Syndrome
- ClinicalTrials.gov ID
- NCT04325321
- Acronym / sponsor ID
- BHS / R01HL149672
- Conditions
- Takotsubo Cardiomyopathy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 66 participants (actual)
- Lead sponsor
- The Miriam HospitalUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 2 Sep 2020 (actual)
- Primary completion
- 11 Nov 2025 (actual)
- Study completion
- 28 Feb 2026 (actual)
- First posted
- 27 Mar 2020 (actual)
- Results
- Posted 29 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goals of this study are as follows:
- To rigorously establish and characterize heterogeneity in the pathophysiology of Takotsubo Syndrome (TS).
- To rigorously test the contribution of TS triggering events and mental stress responsiveness to 1-year prognosis after TS event.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Stress reactivity | Other | Other: Stress reactivity testStress reactivity test |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age >=18
- A new diagnosis of takotsubo syndrome fulfilling Mayo Clinic criteria
- Ability to understand and speak English
Key exclusion criteria (9 listed)
- Inability or unwillingness to give informed consent
- Severe cognitive impairment
- Uncontrolled hypertension
- Acute psychosis
- High suicidal risk
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stress reactivity testThe 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. | Other | Stress reactivity |
Primary outcome
Mean Change (in pg/mL) in Plasma Epinephrine Levels
Time frame: At baseline
Blood samples for plasma epinephrine are collected during the stress reactivity test, 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.
Mean Change (in pg/mL) in Plasma Norepinephrine Levels
Time frame: At baseline
Blood samples for plasma norepinephrine are collected during the stress reactivity test, 10-min into Baseline, 10-min into Emotion Recall, and 18 minutes into Recovery. Change will be calculated by subtracting Baseline epinephrine levels from Emotion Recall norepinephrine levels.
2 secondary outcomes
Change in High Frequency Power Heart Rate Variability (Hf-HRV) in Ln Msec
Time frame: At baseline
Mean Change in Global Longitudinal Strain (GLS)
Time frame: Baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41562264Salmoirago-Blotcher E, Keirns NG, Ouaddi S, Tripolone J, Liu C, Breault C, Dettmer A. Chronic adrenocortical activity and onset of Takotsubo syndrome. Eur J Cardiovasc Nurs. 2026 Jul 28;25(5):1033-1040. doi: 10.1093/eurjcn/zvag023.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elena Salmoirago-Blotcher, MD, PhD principal investigator
The Miriam Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stress reactivity test in people with Takotsubo Cardiomyopathy, run by The Miriam Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Change (in pg/mL) in Plasma Epinephrine Levels (time frame: At baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04325321, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2026; AzTrials last refreshed its copy on 27 Oct 2026.