Characterization of priMary And sEcondary STress Related takOtsubo: the MAESTRO Pilot Study
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.
⁃ 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.