Midwall fibrosis is an independent predictor of mortality and morbidity in patients with DCM undergoing CRT. The outcome of DCM with midwall fibrosis is similar to that of ICM. This relationship is mediated by both pump failure and sudden cardiac death.

Background-Conventional right ventricular (RV) apex pacing can lead to adverse clinical outcome associated with asynchronous activation and reduced left ventricular (LV) pump function. We investigated to what extent alternate RV (septum) and LV (septum, apex) pacing sites improve LV electric activation, mechanics, hemodynamic performance, and efficiency over 4 months of pacing. Methods and Results-After AV nodal ablation, mongrel dogs were randomized to receive 16 weeks of VDD pacing at the RV apex, RV septum, LV apex, or LV septum (transventricular septal approach). Electric activation maps (combined epicardial contact and endocardial noncontact) showed that RV apical and RV septal pacing induced significantly greater electric desynchronization than LV apical and LV septal pacing. RV apex and RV septal pacing also significantly increased mechanical dyssynchrony, discoordination (MRI tagging) and blood flow redistribution (microspheres) and reduced LV contractility, relaxation, and myocardial efficiency (stroke work/myocardial oxygen consumption). In contrast, LV apical and LV septal pacing did not significantly alter these parameters as compared with the values during intrinsic conduction. At 16 weeks, acute intrasubject comparison showed that single-site LV apical and LV septal pacing generally resulted in similar or better contractility, relaxation, and efficiency as compared with acute biventricular pacing. Conclusions-Acute and chronic LV apical and LV septal pacing maintain regional cardiac mechanics, contractility, relaxation, and efficiency near native levels, whereas RV apical or RV septal pacing diminish these variables. Acute LV apical and LV septal pacing tend to maintain or improve contractility and efficiency compared with biventricular pacing. (Circ Arrhythmia Electrophysiol. 2009;2:571-579.)Key Words: pacing Ⅲ hemodynamics Ⅲ mapping Ⅲ mechanics Ⅲ oxygen C ompared with normal ventricular activation, conventional right ventricular (RV) apex pacing is associated with asynchronous left ventricular (LV) activation, abnormal contraction, and reduced pump function (for review, see reference 1). 1 These adverse effects have been associated with an increased risk of developing heart failure (for review, see reference 1). 1 Also contributing to this adverse outcome is a reduction in myocardial efficiency during ventricular pacing, which increases total myocardial oxygen demand. Consequently, paced hearts can be expected to be more susceptible to ischemia when coronary reserve is limited, 2 as during coronary artery disease and/or overload of the heart. Clinical Perspective on p 579Several studies have sought alternative pacing sites to improve hemodynamic performance. Because pacing leads are usually implanted transvenously, alternate sites within the RV have been studied most intensively, but results of the various studies are mixed. 3,4 Experimental and clinical studies indicate that LV pacing sites often render better hemodynamic performance than RV pacing sites. [5][6][7] In a previous acute canine stu...

Background-Heart failure (HF) in combination with mechanical dyssynchrony is associated with a high mortality rate.To quantify contractile dysfunction in patients with HF, investigators have proposed several indices of mechanical dyssynchrony, including percentile range of time to peak shortening (WTpeak), circumferential uniformity ratio estimate (CURE), and internal stretch fraction (ISF). The goal of this study was to compare the sensitivity of these indices to 4 major abnormalities responsible for cardiac dysfunction in dyssynchronous HF: dilation, negative inotropy, negative lusitropy, and dyssynchronous activation. Methods and Results-All combinations of these 4 major abnormalities were included in 3D computational models of ventricular electromechanics. Compared with a nonfailing heart model, ventricles were dilated, inotropy was reduced, twitch duration was prolonged, and activation sequence was changed from normal to left bundle branch block. In the nonfailing heart, CURE, ISF, and WTpeak were 0.97Ϯ0.004, 0.010Ϯ0.002, and 78Ϯ1 milliseconds, respectively. With dilation alone, CURE decreased 2.0Ϯ0.07%, ISF increased 58Ϯ47%, and WTpeak increased 31Ϯ3%. With dyssynchronous activation alone, CURE decreased 15Ϯ0.6%, ISF increased 14-fold (Ϯ3), and WTpeak increased 121Ϯ4%. With the combination of dilation and dyssynchronous activation, CURE decreased 23Ϯ0.8%, ISF increased 20-fold (Ϯ5), and WTpeak increased 147Ϯ5%. Conclusions-Dilation and left bundle branch block combined synergistically decreased regional cardiac function. CURE and ISF were sensitive to this combination, but WTpeak was not. CURE and ISF also reflected the relative nonuniform distribution of regional work better than WTpeak. These findings might explain why CURE and ISF are better predictors of reverse remodeling in cardiac resynchronization therapy. (Circ Heart Fail. 2010;3:528-536.)Key Words: myocardium Ⅲ cardiomyopathy Ⅲ heart failure O f all patients with heart failure (HF) due to left ventricular (LV) systolic dysfunction, those with an additional ventricular dyssynchrony have the worst prognosis. 1 LV dysfunction in dyssynchronous HF (DHF) is partially attributable to the sensitivity of fiber shortening to the activation pattern. In left bundle branch block (LBBB), mechanical contraction becomes dyssynchronous, 2-5 and LBBB with dilation of the LV exacerbates regional and global cardiac dysfunction. 6 In patients with coronary artery disease, the magnitude of LV long-axis shortening, among other mechanical measures, was decreased compared with normal controls. 6 When LV dilation was part of the disease process, function continued to decrease. The greatest loss of function was observed in patients who presented with both dilation and LBBB. 6 It is unclear, however, how interactions among dilation, dyssynchronous activation, and altered contractile properties contribute to deterioration of cardiac function in DHF. Clinical Perspective on p 536Insights into the effects of interactions among these abnormalities on cardiac function can be...

Objectives-To study the impact of biventricular pacing (BiV) and scar size on left ventricular (LV) regional and global function using a detailed finite element model of three-dimensional electromechanics in the failing canine heart. Background-Cardiac resynchronization therapy (CRT) clinical trials have demonstrated that up to 30% of patients may be classified as non-responders. The presence of a scar appears to contribute to those that do not respond to CRT. A recent study in patients with myocardial scar showed that LV dyssynchrony was the sole independent predictor of reverse remodeling, and not scar location or size.Methods-Two activation sequences were simulated: left bundle branch block (LBBB) and acute simultaneous BiV (with leads in the left and right ventricle) in hearts with chronic scars of various sizes. The dependence of regional function (mean fiber ejection strain, variance of fiber isovolumic strain and fraction of tissue stretched during ejection) and global function (left ventricular dP/ dt max , ejection fraction, stroke work) on scar size and pacing protocol was tested.Results-Global function and regional function averaged over the whole LV during LBBB and BiV decreased as a function of scar size. In the non-scarred regions, however, regional function was largely independent of scar size for a fixed pacing site. Conclusions-The model results suggest that uniformity of mechanical contraction in non-scarred regions in the failing heart during biventricular pacing is independent of scar size for a fixed pacing site.

Cardiac resynchronization therapy (CRT) is a promising therapy for heart failure patients with a conduction disturbance, such as left bundle branch block. The aim of CRT is to resynchronize contraction between and within ventricles. However, about 30% of patients do not respond to this therapy. Therefore, a better understanding is needed for the relation between electrical and mechanical activation. In this paper, we focus on to what extent animal experiments and mathematical models can help in order to understand the pathophysiology of asynchrony to further improve CRT.

The excitation-contraction coupling properties of cardiac myocytes isolated from different regions of the mammalian left ventricular wall have been shown to vary considerably, with uncertain effects on ventricular function. We embedded a cell-level excitation-contraction coupling model with region-dependent parameters within a simple finite element model of left ventricular geometry to study effects of electromechanical heterogeneity on local myocardial mechanics and global haemodynamics. This model was compared with one in which heterogeneous myocyte parameters were assigned randomly throughout the mesh while preserving the total amount of each cell subtype. The two models displayed nearly identical transmural patterns of fibre and cross-fibre strains at end-systole, but showed clear differences in fibre strains at earlier points during systole. Haemodynamic function, including peak left ventricular pressure, maximal rate of left ventricular pressure development and stroke volume, were essentially identical in the two models. These results suggest that in the intact ventricle heterogeneously distributed myocyte subtypes primarily impact local deformation of the myocardium, and that these effects are greatest during early systole.

In CRT recipients with ICM, scar and reversible ischemia in or adjacent to LV pacing site were independent predictors of HF hospitalization and death.

We identified a significant correlation between LV-right ventricular interlead distance and LVLED; additionally, both parameters act synergistically in predicting LV anatomic reverse remodeling. Efforts to optimize both interlead distance and electrical delay may improve CRT outcomes.