Ventricular pacing causes a threefold difference in myofiber work within the LV wall. This difference appears large enough to regard local myocardial function as an important determinant for abnormalities in perfusion, metabolism, structure and pump function during asynchronous electrical activation. Pacing at sites that cause more synchronous activation may limit the occurrence of such derangements.

Background-Asynchronous electrical activation, induced by ventricular pacing, causes regional differences in workload, which is lower in early-than in late-activated regions. Because the myocardium usually adapts its mass and structure to altered workload, we investigated whether ventricular pacing leads to inhomogeneous hypertrophy and whether such adaptation, if any, affects global left ventricular (LV) pump function. Methods and Results-Eight dogs were paced at physiological heart rate for 6 months (AV sequential, AV interval 25 ms, ventricular electrode at the base of the LV free wall). Five dogs were sham operated and served as controls. Ventricular pacing increased QRS duration from 47.2Ϯ10.6 to 113Ϯ16.5 ms acutely and to 133.8Ϯ25.2 ms after 6 months. Two-dimensional echocardiographic measurements showed that LV cavity and wall volume increased significantly by 27Ϯ15% and 15Ϯ17%, respectively. The early-activated LV free wall became significantly (17Ϯ17%) thinner, whereas the late-activated septum thickened significantly (23Ϯ12%). Calculated sector volume did not change in the LV free wall but increased significantly in the septum by 39Ϯ13%. In paced animals, cardiomyocyte diameter was significantly (18Ϯ7%) larger in septum than in LV free wall, whereas myocardial collagen fraction was unchanged in both areas. LV pressure-volume analysis showed that ventricular pacing reduced LV function to a similar extent after 15 minutes and 6 months of pacing. Conclusions-Asynchronous activation induces asymmetrical hypertrophy and LV dilatation. Cardiac pump function is not affected by the adaptational processes. These data indicate that local cardiac load regulates local cardiac mass of both myocytes and collagen. (Circulation. 1998;98:588-595.)

The main goal of this article was to review animal experimental work on the effect of asynchronous activation on ventricular pump function. During normal sinus rhythm and atrial pacing, the Purkinje system contributes significantly to the rapid electrical activation of the ventricles. In contrast, during ventricular pacing the impulse is almost exclusively conducted through the normal myocardium. As a consequence, electrical activation of the ventricles becomes asynchronous and has an abnormal sequence. The abnormal impulse conduction causes considerable disturbances to occur in regional systolic fiber shortening, mechanical work, blood flow, and oxygen consumption; low values occurring in early activated regions and values above normal being present in late activated regions. Many animal studies have now shown that the abnormal electrical activation, induced by ventricular pacing, leads to a depression of systolic and diastolic LV function. Pacing at the right ventricular apex (the conventional pacing site) reduces LV function more than pacing at the high ventricular septum or at LV sites. In canine hearts with experimental LBBB, LV pacing significantly improves LV pump function. Differences in LV pump function between (combinations of) pacing sites are poorly correlated with QRS duration. Therefore, the cause of the depression of LV function during abnormal electrical activation appears to be a combination of the asynchrony and the sequence of activation. These experimental findings justify continuing attention for optimizing the site(s) of ventricular pacing in patients with normal and abnormal ventricular impulse conduction.

The temporal evolution of three-dimensional (3-D) strain maps derived from magnetic resonance imaging (MRI) tagging were used to noninvasively evaluate mechanical activation in the left ventricle (LV) while seven canine hearts were paced in situ from three different sites: the base of the LV free wall (LVb), the right ventricular apex (RVa), and the right atrium (RA). Strain maps plotted against time showed the evolution of shortening over the entire LV midwall and were used to generate mechanical activation maps showing the onset of circumferential shortening. RA pacing showed rapid synchronous shortening; LVb pacing showed a wave front of mechanical activation propagating slowly and steadily from the pacing site, whereas RVa pacing showed regions of rapid and slower propagation. The mechanical (M) activation times correlated linearly with the electrical (E) activation (M = 1.06E + 8.4 ms, R = 0.95). The time for 90% activation of the LV was 63.1 ± 24.3 ms for RA pacing, 130.2 ± 9.8 ms for LVb pacing, and 121.3 ± 17.9 ms for RVa pacing. The velocity of mechanical activation was calculated for LVb and RVa pacing and was similar to values reported for electrical conduction in myocardium. The propagation of mechanical activation for RVa pacing showed regional variations, whereas LVb pacing did not.

Clinical trials in patients with pacemakers for sinus node dysfunction or atrioventricular block (AVB) and implantable cardioverter-defibrillators provide increasing evidence showing that desynchronization of ventricular electrical activation and contraction, induced by conventional right ventricular apex (RVA) pacing, is a serious threat for long-term cardiac morbidity and mortality. The risk of heart failure is increased even in hearts with initially normal pump function and in case of part-time ventricular pacing. These epidemiologic data fit with knowledge from decades of pathophysiological research, indicating that right ventricular (RV) pacing creates abnormal contraction, reduced pump function, hypertrophy, and ultrastructural abnormalities. This paper presents a new paradigm that aims to tailor ventricular pacing to the individual patient to achieve a way of pacing that is as physiologic as possible. In patients without AVB and no intraventricular conduction abnormalities, ventricular pacing should be avoided as much as possible, using atrial-based pacing. In patients with AVB, alternate single-site RV or left ventricular pacing or biventricular pacing may be superior to RVA pacing. Efforts to optimize the pacing mode or site should be greater in patients with a longer expected duration of pacing, poorer cardiac function, and larger mechanical asynchrony. Awareness of the problem of desynchronization should also lead to more regular monitoring of cardiac pump function and mechanical asynchrony in any patient with ventricular pacing.

AimsTo develop a novel myocardial deformation index that is highly sensitive to the effect of cardiac resynchronization therapy (CRT) and that can be used to predict response to CRT. Methods and resultsBefore and 6.5 + 2.3 months after implantation of a CRT device, longitudinal shortening and stretch were timed and quantified by speckle tracking echocardiography in a cohort of 62 patients. Distinction was made between systolic total stretch (STS; all systolic stretch) and systolic rebound stretch (SRS; only systolic stretch following initial shortening). Systolic total stretch and SRS could be measured in all wall segments in 41 of 62 patients. Septal SRS quantification was possible in all 62 patients and was performed by a blinded observer. Cardiac resynchronization therapy reduced STS (255 + 30%) but reduced SRS (277 + 21%) significantly more (P , 0.01). The largest amount of baseline SRS and the largest reductions in SRS (290 + 22%) were found in the septum. Reductions in local SRS were paralleled by increases in local systolic shortening that were twice as large (r ¼ 0.79), thereby strongly improving septal function. Baseline values of septal SRS correlated with reductions in left ventricular end-systolic volume index (DLVESVi; r ¼ 0.62) and brain-type natriuretic peptide (BNP) (Dlog 10 BNP; r ¼ 0.57). Septal SRS was an independent predictor of CRT response in linear regression analysis and predicted DLVESVi of 15% with a sensitivity and specificity of 81% at ROC analysis (areas under the curve 0.89 + 0.04). ConclusionSeptal rebound stretch appears to be a sensitive and practical diagnostic criterion to quantify the functional substrate amenable to CRT and to predict response.--

BackgroundMyocardial scarring at the LV pacing site leads to incomplete resynchronization and a suboptimal symptomatic response to CRT. We sought to determine whether the use of late gadolinium cardiovascular magnetic resonance (LGE-CMR) to guide left ventricular (LV) lead deployment influences the long-term outcome of cardiac resynchronization therapy (CRT).Methods559 patients with heart failure (age 70.4 ± 10.7 yrs [mean ± SD]) due to ischemic or non-ischemic cardiomyopathy underwent CRT. Implantations were either guided (+CMR) or not guided (-CMR) by LGE-CMR prior to implantation. Fluoroscopy and LGE-CMR were used to localize the LV lead tip and and myocardial scarring retrospectively. Clinical events were assessed in three groups: +CMR and pacing scar (+CMR+S); CMR and not pacing scar (+CMR-S), and; LV pacing not guided by CMR (-CMR).ResultsOver a maximum follow-up of 9.1 yrs, +CMR+S had the highest risk of cardiovascular death (HR: 6.34), cardiovascular death or hospitalizations for heart failure (HR: 5.57) and death from any cause or hospitalizations for major adverse cardiovascular events (HR: 4.74) (all P < 0.0001), compared with +CMR-S. An intermediate risk of meeting these endpoints was observed for -CMR, with HRs of 1.51 (P = 0.0726), 1.61 (P = 0.0169) and 1.87 (p = 0.0005), respectively. The +CMR+S group had the highest risk of death from pump failure (HR: 5.40, p < 0.0001) and sudden cardiac death (HR: 4.40, p = 0.0218), in relation to the +CMR-S group.ConclusionsCompared with a conventional implantation approach, the use of LGE-CMR to guide LV lead deployment away from scarred myocardium results in a better clinical outcome after CRT. Pacing scarred myocardium was associated with the worst outcome, in terms of both pump failure and sudden cardiac death.

During ventricular pacing, LV pump function is maintained best (i.e., at SR level) when pacing at the LV septum or LV apex, potentially because pacing from these sites creates a physiological propagation of electrical conduction.