Atrial fibrillation (AF) is a major cause of cardiovascular morbidity and mortality. To early detect and to avoid AF-related complications, several cardiac imaging modalities and approaches aim to... Show moreAtrial fibrillation (AF) is a major cause of cardiovascular morbidity and mortality. To early detect and to avoid AF-related complications, several cardiac imaging modalities and approaches aim to quantify the severity of the underlying atrial cardiomyopathy (i.e., the extent of atrial remodeling). However, most established cardiac imaging modalities just incorporate single components of atrial remodeling and do not reflect the complete multifactorial process, which may contribute to their limited predictive value. Echocardiography-derived PA-TDI duration is a sophisticated echocardiographic parameter to assess total atrial conduction time and directly reflects both electrical and structural changes to the atria. Therefore, PA-TDI duration provides a more comprehensive quantification of the extent of atrial remodeling than other imaging modalities. In this article we review the role of PA-TDI duration as a marker of atrial remodeling and summarize the available data on PA-TDI duration to identify patients at risk for AF, as well as to guide AF management. Moreover, we discuss how to assess PA-TDI duration and provide recommendations on the implementation of PA-TDI duration into routine clinical care. Graphic abstract Show less
Reil, J.C.; Reil, G.H.; Kovacs, A.; Sequeira, V.; Waddingham, M.T.; Lodi, M.; ... ; Hamdani, N. 2020
Key pointsThe Anrep effect represents the alteration of left ventricular (LV) contractility to acutely enhanced afterload in a few seconds, thereby preserving stroke volume (SV) at constant preload... Show moreKey pointsThe Anrep effect represents the alteration of left ventricular (LV) contractility to acutely enhanced afterload in a few seconds, thereby preserving stroke volume (SV) at constant preload. As a result of the missing preload stretch in our model, the Anrep effect differs from the slow force response and has a different mechanism. The Anrep effect demonstrated two different phases. First, the sudden increased afterload was momentary equilibrated by the enhanced LV contractility as a result of higher power strokes of strongly-bound myosin cross-bridges. Second, the slightly delayed recovery of SV is perhaps dependent on Ca2+/calmodulin-dependent protein kinase II activation caused by oxidation and myofilament phosphorylation (cardiac myosin-binding protein-C, myosin light chain 2), maximizing the recruitment of available strongly-bound myosin cross-bridges. Short-lived oxidative stress might present a new facet of subcellular signalling with respect to cardiovascular regulation. Relevance for human physiology was demonstrated by echocardiography disclosing the Anrep effect in humans during handgrip exercise. The present study investigated whether oxidative stress and Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity are involved in triggering the Anrep effect. LV pressure-volume (PV) analyses of isolated, preload controlled working hearts were performed at two afterload levels (60 and 100 mmHg) in C57BL/6N wild-type (WT) and CaMKII-double knockout mice (DKOCaMKII). In snap-frozen WT hearts, force-pCa relationship, H(2)O(2)generation, CaMKII oxidation and phosphorylation of myofilament and Ca(2+)handling proteins were assessed. Acutely raised afterload showed significantly increased wall stress, H(2)O(2)generation and LV contractility in the PV diagram with an initial decrease and recovery of stroke volume, whereas end-diastolic pressure and volume, as well as heart rate, remained constant. Afterload induced increase in LV contractility was blunted in DKOCaMKII-hearts. Force development of single WT cardiomyocytes was greater with elevated afterload at submaximal Ca(2+)concentration and associated with increases in CaMKII oxidation and phosphorylation of cardiac-myosin binding protein-C, myosin light chain and Ca(2+)handling proteins. CaMKII activity is involved in the regulation of the Anrep effect and associates with stimulation of oxidative stress, presumably starting a cascade of CaMKII oxidation with downstream phosphorylation of myofilament and Ca(2+)handling proteins. These mechanisms improve LV inotropy and preserve stroke volume within few seconds. Show less
