Mechanism and diagnosis of left ventricular diastolic dysfunction

Diastolic dysfunction is a condition in which ventricular lling is impaired, regardless of the presence of symptoms and irrespective of whether the ejection fraction is normal or reduced. Left ventricular diastolic dysfunction results from complex and interconnected biochemical and cellular mechanisms. Among them, impaired myocardial relaxation due to calcium dysregulation, altered titin phosphorylation affecting the passive elasticity of the myocardium, and extracellular matrix remodeling with the development of brosis mediated by signalling pathways such as TGF-/SMAD and MAPK play a leading role. Additional contributing factors include oxidative stress and mitochondrial dysfunction, chronic in ammation and activation of cytokine cascades, metabolic disturbances such as diabetes and obesity, as well as protein dysfunction related to endoplasmic reticulum stress and impaired proteolysis. All these processes in complex lead to impaired diastolic lling of the left ventricle, i.e., diastolic dysfunction. Due to its broad availability and proven clinical value, echocardiography is the primary method for diagnosing diastolic dysfunction. Invasive and other imaging modalities offer complementary information in complex or borderline cases, or when echocardiographic evaluation is dif cult or impossible.