Characterization of priMary And sEcondary STress Related takOtsubo
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorFondazione Policlinico Universitario Agostino Gemelli IRCCS
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Positron Emission Tomography (PET) analysis
Diagnostic test18F-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.
Blood samples collection
Diagnostic testAt 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.
Clinical follow up visit
Other interventionParticipation 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.
Treatment groups
60 Participants
are divided into 2 treatment groupsGroup A: Takotsubo SyndromeExperimental treatment 3 interventions
Group B: Septic patientsExperimental treatment 1 intervention
Trial outcomes
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.
Time frame
3 monthsSecondary outcomes
1
Association between hair cortisol levels and Takotsubo clinical profile
To evaluate hair cortisol levels in patients affected by primary vs secondary TTS. Hair cortisol levels will be measured as cortisol concentration in the hair (pg/ml).
Time frame
Up to 30 days2
Association between IL-6 and Takotsubo clinical profile
To assess if different serum levels of IL-6 can be assessed in patients affected by primary vs secondary TTS, helping in differentiating the two clinical phenotypes. IL-6 levels will be measured both in the acute setup and at 3 months follow-up as serum concentration (pg/mL).
Time frame
Up to 3 months3
Association between IL-1beta and Takotsubo clinical profile
To assess if different serum levels of IL-1beta can be assessed in patients affected by primary vs secondary TTS, helping in differentiating the two clinical phenotypes. IL-1beta levels will be measured both in the acute setup and at 3 months follow-up as serum concentration (pg/mL).
Time frame
Up to 3 months4
Association between IL-10 and Takotsubo clinical profile
To assess if different serum levels of IL-10 can be assessed in patients affected by primary vs secondary TTS, helping in differentiating the two clinical phenotypes. IL-10 levels will be measured both in the acute setup and at 3 months follow-up as serum concentration (pg/mL).
Time frame
Up to 3 monthsSponsors and contacts
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Source ClinicalTrials.gov