Characterization of priMary And sEcondary STress Related takOtsubo

NCT05793008 | Recruiting

• 1 other identifier: 5469
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Takotsubo syndrome (TTS) is an acute and reversible form of myocardial injury often preceded by a physical or emotional trigger. Although TTS was generally considered a benign disease for its reversible nature, it is now clear that hemodynamic and electrical instability during the acute phase exposes patients to frequent serious adverse in-hospital complications. However, the pathophysiology of TTS is far from being completely understood. Consistent evidence demonstrated that the environmental events experienced by most of these patients and perceived as stressful (both physical or emotional) induce a brain activation and a stress-related response, with increasing bioavailability of local and circulating stress mediators, such as catecholamine and cortisol, which showed to play a major role in the etiology of to the "neurogenic stunning myocardium" responsible for this clinical condition. Primary and secondary TTS showed an important clinical heterogeneity identifying two different subtypes of patients with different outcomes and risk profiles. the invastigators hypothesize that a different activation of the brain structures involved in acute stress response, as well as a different exposure to chronic stress, may subtend the different clinical and risk profiles observed in primary vs. secondary TTS patients. Moreover, the invastigators hypothesize that distinct signatures of circulating biomarkers may be associated with these two categories of TTS patients. Therefore, identifying these specific signatures may help in the diagnosis of these patients and pave the way for the identification of specific pathophysiologic pathways and the development of future therapies.

Conditions

Takotsubo Cardiomyopathy; Sepsis-induced Cardiomyopathy

Keywords

Takotsubo Syndrome; Fisical trigger; Emotional trigger; Biomarker; Precision Medicine; Neuroimaging approach

Outcome Measures

Primary Outcomes (1)

• Association between brain activation and clinical profile and outcome in Takotsubo Syndrome

  To establish through an 18F-FDG-PET/CT analysis of brain structures involved in acute stress response if a different brain activation subtends to primary or secondary TTS. Brain activation will be evaluated through the tracer (18F-FDG) accumulation in the brain measured as standardized uptake value (SUV) and compared between the two subgroups.

  3 months

Secondary Outcomes (17)

• Association between hair cortisol levels and Takotsubo clinical profile

  Up to 30 days

• Association between IL-6 and Takotsubo clinical profile

  Up to 3 months

• Association between IL-1beta and Takotsubo clinical profile

  Up to 3 months

• Association between IL-10 and Takotsubo clinical profile

  Up to 3 months

• Association between IL-18 and Takotsubo clinical profile

  Up to 3 months

Study Arms (2)

Takotsubo Syndrome

EXPERIMENTAL

Patients diagnosed with either primary or secondary Takotsubo Syndrome. TTS diagnosed based on modified Mayo Clinic Diagnostic Criteria as: * Transient wall motion abnormality in the left ventricle beyond a single epicardial coronary artery distribution; * Absence of obstructive coronary artery disease or angiographic evidence of acute plaque rupture, which can explain the wall motion abnormality; * New electrocardiographic abnormalities or elevation in cardiac troponin values; * Absence of pheochromocytoma or myocarditis.

Diagnostic Test: Positron Emission Tomography (PET) analysis; Diagnostic Test: Blood samples collection; Other: Clinical follow up visit

Septic patients

EXPERIMENTAL

Patients with diagnosis of sepsis and septic shock with or without concurrent LVSD or/and LVDD. Diagnosis of sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, which can be represented by an increase in the Sequential \[Sepsis-related\] Organ Failure Assessment (SOFA) score of 2 points or more. Septic shock, defined as vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (\>18 mg/dL) in the absence of hypovolemia. Sepsis-induced cardiomyopathy, defined as left ventricular systolic dysfunction (LVSD) and/or LV diastolic dysfunction (LVDD) following sepsis in patients without known structural or functional cardiac disease.

Diagnostic Test: Blood samples collection

Interventions

Positron Emission Tomography (PET) analysis DIAGNOSTIC_TEST

18F-FDG-PET/CT imaging will be performed 3 months after the acute event at the Department of Nuclear Medicine of Fondazione Policlinico Universitario A. Gemelli IRCCS using an integrated scanner. Intravenous 18F-FDG (370 MBq) will be given following an overnight fast. Three-dimensional PET imaging will be performed after 1 h of quiet waiting. A non-gated, non-contrast CT will be acquired for attenuation correction. Brain structures analyzed will include the neocortex, limbic system (insula, amygdala, cingulate cortex, and hippocampus), reticular formation, brainstem, and spinal cord.

Takotsubo Syndrome

Blood samples collection DIAGNOSTIC_TEST

At the time of coronary angiography for patients with primary or secondary TTS and within the first 48 hours for patients with sepsis or septic shock, arterial blood samples will be collected in 1 Vacuette® 9 mL CAT Serum Clot Activator tube and 4 Vacuette® 6 mL EDTA tubes. Furthermore, a hair sample of 6 cm will be collected for hair cortisol assay. For patients with primary or secondary TTS blood samples will be collected by venipuncture with 1 Vacuette® 9 mL CAT Serum Clot Activator tube and 4 Vacuette® 6 mL EDTA tubes also at 3 months follow-up. Blood samples will be immediately centrifuged to obtain whole blood, serum, and plasma samples, and then aliquoted into Eppendorf-type tubes. All samples will then be stored at -80°C until the analysis.

Septic patients; Takotsubo Syndrome

Clinical follow up visit OTHER

Participation in this study requires for patients with primary vs secondary TTS, a follow-up visit at 3 months (90 +/- 5 gg) after enrollment to assess a Positron Emission Tomography (PET) analysis, and during the same visit, venous blood sampling as described above will be further performed.

Takotsubo Syndrome

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For patients with TTS:
• Informed consent signed by the patient or parent/guardian/legal representative.
• TTS diagnosed based on modified Mayo Clinic Diagnostic Criteria as: (i) transient wall motion abnormality in the left ventricle beyond a single epicardial coronary artery distribution; (ii) absence of obstructive coronary artery disease or angiographic evidence of acute plaque rupture, which can explain the wall motion abnormality; (iii) new electrocardiographic abnormalities or elevation in cardiac troponin values; (iv) absence of pheochromocytoma or myocarditis. N.B. - All TTS diagnosis made according to Mayo Clinic Diagnostic Criteria will be a posterior compared to fulfil the new InterTAK Diagnostic Criteria (19). Myocarditis will be suspected based on clinical presentation (e.g. previous flu-like symptoms, increased inflammatory biomarkers) and confirmed by cardiac magnetic resonance.N.B. - Of note, primary TTS mainly concerns post-menopausal women with symptoms resulting from myocardial damage, emotional trigger, and evidence of normal coronary arteries at coronary angiography, whilst secondary TTS equally affects men and women, with physical triggers and in the presence of possible coronary artery disease at coronary angiography.
• For patients with sepsis:
• Informed consent signed by the patient or parent/guardian/legal representative.
• Diagnosis of sepsis, defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, which can be represented by an increase in the Sequential \[Sepsis-related\] Organ Failure Assessment (SOFA) score of 2 points or more.
• Septic a shock, defined as vasopressor requirement to maintain a mean arterial pressure of 65 mmHg or greater and serum lactate level greater than 2 mmol/L (\>18 mg/dL) in the absence of hypovolemia.
• Sepsis-induced cardiomyopathy, defined as left ventricular systolic dysfunction (LVSD) and/or LV diastolic dysfunction (LVDD) following sepsis in patients without known structural or functional cardiac disease.

You may not qualify if:

• Alternate diagnosis for the clinical presentation.
• Contraindication to PET for patients with TTS (pregnancy, breast-feeding or patients considering becoming pregnant during the study period);
• Patients with comorbidities having an expected survival \<1-year.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS

Rome, 00168, Italy

RECRUITING

Related Publications (21)

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• Templin C, Hanggi J, Klein C, Topka MS, Hiestand T, Levinson RA, Jurisic S, Luscher TF, Ghadri JR, Jancke L. Altered limbic and autonomic processing supports brain-heart axis in Takotsubo syndrome. Eur Heart J. 2019 Apr 14;40(15):1183-1187. doi: 10.1093/eurheartj/ehz068.

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MeSH Terms

Conditions

Takotsubo Cardiomyopathy

Interventions

Positron-Emission Tomography

Condition Hierarchy (Ancestors)

Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Ventricular Dysfunction, Left; Ventricular Dysfunction

Intervention Hierarchy (Ancestors)

Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Image Enhancement; Photography; Radionuclide Imaging; Tomography; Diagnostic Techniques, Radioisotope

Study Officials

• Rocco A Montone, MD, PhD

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rocco A Montone, MD, PhD

CONTACT

+39-0630154187; roccoantonio.montone@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: IRCCS Researcher

Study Record Dates

• First Submitted: March 3, 2023
• First Posted: March 31, 2023
• Study Start: March 30, 2023
• Primary Completion: March 2, 2026
• Study Completion (Estimated): September 2, 2026
• Last Updated: February 26, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)