Pathobiology of cardiac dyssynchrony and resynchronization therapy

Abstract

Synchronous ventricular electrical activation is a prerequisite for adequate left ventricular (LV) systolic function. Conduction abnormalities such as left bundle branch block, and ventricular pacing lead to a dyssynchronous electrical activation sequence, which may have deleterious consequences. The present review attempts to connect the various processes involved in the development of 'dyssynchronopathy', and its correction by cardiac resynchronization therapy (CRT). Abnormal electrical impulse conduction leads to abnormal contraction, characterized by regional differences in timing as well as shortening patterns and amount of external work performed. Early activated regions may show 'wasted work', which leads to inefficient action of the entire left ventricle. Moreover, both the development of heart failure (HF) in general and the regional differences in mechanical load lead to structural, electrical, and contractile remodelling processes. These have been demonstrated at the level of the myocardium (asymmetric hypertrophy, fibrosis, prolongation of activation and reduction in repolarization forces, decrease in LV ejection fraction), cell (gap junctional remodelling, derangement of the T-tubular structure), and molecule (under or overexpression of ion channels and contractile proteins subtypes and abnormal calcium handling). The myocardial adaptations to dyssynchrony are 'maladaptive'. This also explains why CRT, unlike most pharmacological treatments, continues to increase its therapeutic effect over time. Finally, better understanding of all processes involved in dyssynchrony and CRT may also lead to new pharmacological agents for treating HF and to novel pacing strategies.

A novel index combining diastolic and systolic tissue Doppler parameters for predicting cardiac resynchronization therapy response

“…Recent studies evaluated the systolic rebound stretch (SRS) for CRT response. 20,21 They found that CRT improves systolic function by converting SRS into shortening. CRT reduces SRS and increases systolic shortening of the septum and increased left ventricular systolic function.…”

“…Septal SRS was predictor for CRT response. 20,21 Increased SPS was related with dyssynchrony, and decreased SPS was related with extensive scar. Patients with large left ventricular scar tissue and low SPS values do not respond to CRT.…”

The Left and Right Ventricles Respond Differently to Variation of Pacing Delays in Cardiac Resynchronization Therapy: A Combined Experimental- Computational Approach

“…Previous work from our group showed that chronic total AV-block leads to structural changes (hypertrophy) and electrical remodeling (QT-time prolongation), but normal contractility (Peschar et al, 2003). On the other hand, patients treated with CRT have different levels of myocardial remodeling and heart failure, which may affect the response to pacing (Strik et al, 2013a, Nguyên et al, 2018). Results of this study might differ from patient data since long-term structural remodeling was not included in both the animal and computational experiments.…”

QRS Complex Wavelet Analysis Can Distinguish Patients with and without Heart Failure, in the Presence of Left Bundle Branch Block

“…LBBB is associated with poor electromechanical function of the left ventricle, as regional delays in depolarization cause dyssynchronous activation of the ventricular walls. Reduced systolic shortening in regions of the myocardium that depolarize early during systole has been observed as the cause of poorer LV function in the setting of LBBB [7]. Cardiac resynchronization therapy (CRT) is performed by pacing both ventricles and is very effective at ceasing and even undoing the deleterious effects of LBBB on cardiac function and remodeling [8].…”