Figure 2 - available via license: CC BY-NC
Content may be subject to copyright.
Source publication
Cardiac resynchronisation therapy is a cornerstone in the treatment of advanced dyssynchronous heart failure. However, despite its widespread clinical application, precise mechanisms through which it exerts its beneficial effects remain elusive. Several studies have pointed to a metabolic component suggesting that, both in concert with alterations...
Context in source publication
Context 1
... such, an overarching hypothesis could be that alleviation by resynchronisation of the increased strain imposed on cardiomyocytes by dyssynchrony, which led to compensatory alterations/remodelling of sarcomeres and triggered changes in bioenergetics, now leads to altered input from specialised mechanosensors that is transduced to the cell, triggering the beneficial effects. 53,190 A depiction of our current partial understanding of this link is attempted in Figure 2. ...
Similar publications
Citations
... Regarding diastolic function, ventricular dyssynchrony leads to an elongation of the left ventricle's pressure decay and prolongs the time it takes for the ventricle to relax without any change in volume, hence reducing the time available for left ventricular diastolic filling. Tachycardic pacing results in diastolic stiffening as a consequence of incomplete left ventricular relaxation caused by an abbreviated filling time [59,60]. Similar to other patients with heart failure and lower ejection fraction, individuals with ventricular dyssynchrony will undergo a compensatory increase in left ventricular (LV) filling pressures [24]. ...
Cardiac conduction involves electrical activity from one myocyte to another, creating coordinated contractions in each. Disruptions in the conducting system, such as left bundle branch block (LBBB), can result in premature activation of specific regions of the heart, leading to heart failure and increased morbidity and mortality. Structural alterations in T-tubules and the sarcoplasmic reticulum can lead to dyssynchrony, a condition that can be treated by cardiac resynchronization therapy (CRT), which stands as a cornerstone in this pathology. The heterogeneity in patient responses underscored the necessity of improving the diagnostic approach. Vectocardiography, ultra-high-frequency ECG, 3D echocardiography, and electrocardiographic imaging seem to offer advanced precision in identifying optimal candidates for CRT in addition to the classic diagnostic methods. The advent of His bundle pacing and left bundle branch pacing further refined the approach in the treatment of dyssynchrony, offering more physiological pacing modalities that promise enhanced outcomes by maintaining or restoring the natural sequence of ventricular activation. HOT-CRT emerges as a pivotal innovation combining the benefits of CRT with the precision of His bundle or left bundle branch area pacing to optimize cardiac function in a subset of patients where traditional CRT might fall short.
... Currently, the presence and degree of dyssynchrony are determined by QRS morphology and duration (≥120 or ≥130 msec per guidelines [1,2]). Beyond the wellknown and intuitive mechanical effects of simultaneous blood expulsion and benefits to energy efficiency of preventing early contraction against yielding sections, as well as late contraction of the latter from an unfavourable (in terms of Frank-Starling principle) overstretched initial condition, several additional pathways have been elucidated [3]. In short, applying CRT to dyssynchronous heart failure (DyssHF) improves cellular bioenergetics by altering expression levels of key cellular metabolism-related proteins, thus promoting aero-bic glycolysis in mitochondria, and by allowing for restoration of myosin isomorphs expression pattern. ...
Cardiac resynchronization therapy (CRT) constitutes a cornerstone to the treatment of advanced dyssynchronous heart failure (DyssHF); moreover it represents one of the few instances that a revolutionary approach was pursued, yielding previously unfathomable benefits to patients out of realistic therapeutic options. However, as is rather extensively established, nonresponse, or even negative response, to CRT continue to plague its course, precluding favourable effects in up to 40% of recipients, for a multitude of reasons. Given the scope of the issue of nonresponse, attempts to negate it by means of altering CRT delivery mode, and, more specifically, by introducing multipoint left ventricular pacing (MPP) have been focused on. Possible reasons for divergent trial results will be presented, as well as potential criteria for predicting whether MPP activation may reap additional benefits as compared to conventional biventricular pacing (BVP). Finally, an alternative framework for approaching CRT in general will be put forward, including advancements which in the (near) future may once more revolutionise heart failure treatment.
... As anticipated, resynchronization effects are markedly greater in cases of true LBBB (17), also reflected in relevant guidelines recommendation levels for CRT use in various forms of intraventricular conduction aberrations (6). Finally, restoration of synchronous activation has significant effects on cardiomyocyte energetics (18), stemming from alleviation of supraphysiological cardiomyocyte stretch/stress levels, allowing for restoration of proper cellular metabolism/function. However, current implementation of CRT, with delivery of an LV pulse through a coronary sinus (CS)-residing multipolar electrode appears to solely focus on LV, rather than cardiac, function. ...
Cardiac resynchronization therapy constitutes a cornerstone in advanced heart failure treatment, when there is evidence of dyssynchrony,
especially by electrocardiography. However, it is plagued both by persistently high (~30%) rates of nonresponse and by deterioration of right
ventricular function, owing to iatrogenic dyssynchrony in the context of persistent apical pacing to ensure delivery of biventricular pacing. Left
ventricular pacing has long been considered an alternative to standard biventricular pacing and can be achieved as easily as inserting a single
pacing electrode in the coronary sinus. Although monoventricular left ventricular pacing has been proven to yield comparable results with the
standard biventricular modality, it is the advent of preferential left ventricular pacing, combining both the powerful resynchronization potential of
multipolar coronary sinus and right-sided electrodes acting in concert and the ability to preserve intrinsic, physiological right ventricular activation. In this review, we aim to present the underlying principles and modes for delivering left ventricular pacing, as well as to highlight advantages of preferential over monoventricular configuration. Finally, current clinical evidence, following implementation of automated algorithms, regarding performance of left ventricular as compared with biventricular pacing will be discussed. It is expected that the field of preferential left ventricular pacing will grow significantly over the following years, and its combination with other advanced pacing modalities may promote clinical status and prognosis of patients with advanced dyssynchronous heart failure.
Clinical trials have shown that electric stimulation (ELSM) using either cardiac resynchronization therapy (CRT) or cardiac contractility modulation (CCM) approaches is an effective treatment for patients with moderate to severe heart failure, but the mechanisms are incompletely understood. Extracellular vesicles (EV) produced by cardiac mesenchymal stem cells (C-MSC) have been reported to be cardioprotective through cell-to-cell communication. In this study, we investigated the effects of ELSM stimulation on EV secretion from C-MSCs (C-MSCELSM). We observed enhanced EV-dependent cardioprotection conferred by conditioned medium (CM) from C-MSCELSM compared to that from non-stimulated control C-MSC (C-MSCCtrl). To investigate the mechanisms of ELSM-stimulated EV secretion, we examined the protein levels of neutral sphingomyelinase 2 (nSMase2), a key enzyme of the endosomal sorting complex required for EV biosynthesis. We detected a time-dependent increase in nSMase2 protein levels in C-MSCELSM compared to C-MSCCtrl. Knockdown of nSMase2 in C-MSC by siRNA significantly reduced EV secretion in C-MSCELSM and attenuated the cardioprotective effect of CM from C-MSCELSM in HL-1 cells. Taken together, our results suggest that ELSM-mediated increases in EV secretion from C-MSC enhance the cardioprotective effects of C-MSC through an EV-dependent mechanism involving nSMase2.
Objectives: The aim of this study was to assess the capacity of optimized multipoint pacing (MPP) over optimized cardiac resynchronization therapy (CRT), in terms of clinical, functional, and echocardiographic parameters among patients with dyssynchronous heart failure (HF). Methods: Eighty patients (Caucasian, 77.5% male, 68.4 ± 10.1 years, and 53.8% ischemic cardiomyopathy) sequentially received optimized CRT and optimized MPP over 6- and 12-month periods in a single-arm clinical trial. Clinical, laboratory, and echocardiographic assessment was conducted at baseline and after the completion of each step. Results: Significant additive effects of optimized MPP over optimized CRT were noted with regard to 6-min walking distance (baseline/optCRT/optMPP: 293 ± 120 m vs 367 ± 94 m vs 405 ± 129 m and p
