Pathogenesis of the Left Ventricular Diastolic Dysfunction: The Immune System Keeps Playing at the Backstage

Left ventricular diastolic dysfunction (LVDD) with preserved LV systolic function is a cardiac derangement that plays a predominant role in the development of heart failure (HF), with a condition of low-grade inflammation responsible for the main pathogenic mechanism. Such low-grade inflammation causes myocardium remodelling and stiffening. Such myocardial alterations imply abnormalities of the relaxation of the myocytes (the passive relaxation titin driven) but most importantly at the same time increased deposition of myocardial connective tissue by fibroblasts or more rarely, interstitial accumulation of other substances: amyloid fibrils in amyloidosis, eosinophilic cell infiltration with reactive fibrosis in eosinophilic syndrome, Fe++ ion deposition with reactive fibrosis in hemochromatosis, intracellular lipids (like glycosphingolipids) in Fabry disease and finally granulomatous infiltration that can be found in a patchy or multifocal distribution in sarcoidosis. Such myocardial fibrotic derangement causes myocardial stiffness. The abnormal extracellular meshwork that normally works as support for myocyte function now hampers myocardial cell function and increase stiffness of the chamber. As a consequence of increased stiffness of the myocardium, the LV filling process occurs with increasingly higher pressure, which is transmitted back to the pulmonary capillary causing pulmonary congestion and oedema, hypoxemia and finally, secondary pulmonary hypertension and right ventricular dysfunction.