Included in the cytotoxic sequela of catecholamine toxicity is the molecular transformation of the cardiac myocyte to produce apical stunning. Mid-ventricular obstruction, apical stunning: It has been suggested that a mid-ventricular wall thickening with outflow obstruction is important in the pathophysiology. This stunning is largely seen as a protective effect produced by the flood of excess catecholamines into the cardiac muscle cell. Overstimulation of catecholamine receptors create physiological changes in the receptor which has an inverse effect on cardiac cellular function. Termed cellular-trafficking, this property of the cardiac muscle cell is actually a molecular transformation of the cell to produce a down-regulation of catecolaminergic sensitivity. This means that in the presence of excess epinephrine, a normal cardiac contraction is inhibited in an effort to reduce energy demands, prevent hyperactivity and spare the integrity of the cell. Further bolstering this idea is the concentration of these kinds of receptors in the heart. Higher concentrations of the receptor effected to produce cardiac stunning are found closer to the apex of the ventricle. This is what creates the classic ballooning effect of the ventricle.It is likely that there are multiple factors at play that could include some amount of vasospasm and failure of the microvasculature. These factors can overlap and create the complex sequela leading to ischemia and left ventricle contraction abnormality. For instance, estrogen, which confers protection to women by improving blood flow to heart muscle, is one biochemical pathway implicated in the TTS disease process.
Once this protective mechanism is reduced through the decreased production of estrogen after menopause, there is thought to be an increase in endothelial dysfunction predisposing an individual to vasoconstriction and cardiac ischemia. An inciting stressful event elicits the release of catecholamines into the blood stream to create increased heart muscle activity and metabolism. This leads to further cardiac microvascular endothelial dysfunction through oxidative stress, alteration of ion-mediated channels, and electrolyte disturbances which ultimately alter myocardial cell membrane permeability and dysfunction. Coupled with direct heart muscle toxicity, this crescendo of factors are implicated in the ballooning and heart failure characteristically seen in TTS.A 2019 case involved a 60-year-old woman presenting with Takotsubo cardiomyopathy due to over-consumption of wasabi, mistaking it for avocado. Diagnosis
Several well regarded institutions of medical research have produced clinical criteria useful in diagnosing TTS. One of the first sets of guidelines was initially published in 2004 and again in 2008 by the Mayo Clinic. Other research institutions proposing diagnostic criteria include the Japanese Takotsubo Cardiomyopathy Study Group, Gothenburg University, Johns Hopkins University, the Takotsubo Italian Network and the Heart Failure Associates TTS Taskforce of the European Society of Cardiology. All of the research institutions agree on at least two main criteria needed to accurately diagnose TTS: 1) transient left ventricular wall motion abnormality and 2) the absence of a condition obviously explaining this wall motion abnormality (coronary artery lesion, hypoperfusion, myocarditis, toxicity, etc.).