Systolic Improvement and Mechanical Resynchronization Does Not Require Electrical Synchrony in the Dilated Failing Heart With Left Bundle-Branch Block

Leclercq, Christophe; Faris, Owen P.; Tunin, Richard S.; Johnson, Jennifer; Kato, Ritsuchi; Evans, F.J.; Spinelli, Julio; Halperin, Henry R.; McVeigh, Elliot R.; Kass, David A.

doi:10.1161/01.cir.0000035037.11968.5c

Cited by 430 publications

(332 citation statements)

References 20 publications

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“…10 Fusion with electrical activity from the AV node is a possibility [11][12][13] ; however, experimental data have suggested that electrical synchrony is not a prerequisite for mechanical synchrony. 14 Another possible explanation is that early activation of the lateral wall is preferable to the septum, ie, that dyssynchrony associated with right bundle-branch block-type delay is less than that associated with left bundle-branch block-type delay. 10 This is consistent with regional motion analysis of left versus right bundle-branch block, where initial prestretch of the opposing wall is greater with early septal activation.…”

Section: Discussionmentioning

confidence: 99%

Short-Term Effects of Right-Left Heart Sequential Cardiac Resynchronization in Patients With Heart Failure, Chronic Atrial Fibrillation, and Atrioventricular Nodal Block

Hay¹,

Melenovský²,

Fetics³

et al. 2004

Circulation

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115

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Background-Single-site ventricular pacing in patients with heart failure, atrial fibrillation, and severe atrioventricular (AV) nodal block risks the generation of discoordinate contraction. Whether altering the site of stimulation can offset this detrimental effect and what role sequential right ventricular-left ventricular (RV-LV) stimulation might play in such patients remain unknown. Methods and Results-Nine subjects with heart failure (ejection fraction, 14% to 30%), atrial fibrillation, and AV block were studied by pressure-volume analysis. Ventricular stimulation was applied to the RV (apex and outflow tract), LV free wall, and biventricular (BiV) at 80 and 120 bpm. BiV improved systolic function more than either site alone (dP/dt max , 810Ϯ83, 924Ϯ98, 983Ϯ102 mm Hg/s for RV, LV, BiV, respectively; PϽ0.05), although LV pacing was significantly better than RV pacing. However, only BiV improved diastolic function (isovolumic relaxation) over RV or LV alone. Similar results were obtained for both heart rates. RV pacing site did not alter the BiV effect, and concomitant stimulation of both RV sites did not improve function over each alone. Finally, varying RV-LV delay revealed optimal responses with simultaneous pacing. Conclusions-Simultaneous BiV pacing acutely enhances both systolic and diastolic function over single-site RV or LV pacing in congestive heart failure patients with atrial fibrillation and advanced AV block. Sequential RV-LV stimulation offers minimal benefit on average and should perhaps be considered only in targeted subsets such as nonresponding patients.

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Section: Discussionmentioning

confidence: 99%

Short-Term Effects of Right-Left Heart Sequential Cardiac Resynchronization in Patients With Heart Failure, Chronic Atrial Fibrillation, and Atrioventricular Nodal Block

Hay¹,

Melenovský²,

Fetics³

et al. 2004

Circulation

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115

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“…MR 3D tagged images were obtained (GE Signa 1.5T) during either RA or RV free-wall stimulation, and mechanical dyssynchrony indexed by a circumferential uniformity ratio estimate (CURE), as described previously. 9 Perfectly synchronous or dyssynchronous contraction patterns yield CURE indices of 1 or 0, respectively.…”

Section: Assessment Of Mechanical Dyssynchronymentioning

confidence: 99%

Regional Alterations in Protein Expression in the Dyssynchronous Failing Heart

et al. 2003

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Background-Left ventricular (LV) mechanical dyssynchrony induces regional heterogeneity of mechanical load and is an independent predictor of mortality and sudden death in heart failure (HF) patients. We tested whether dyssynchrony also induces localized disparities in the expression of proteins involved with mechanical stress, function, and arrhythmia susceptibility. Methods and Results-Eleven dogs underwent tachycardia-induced HF pacing, either from the right atrium or high right ventricular free wall. Whereas global LV dysfunction was similar between groups, LV contractile coordination assessed by tagged MRI was markedly dyssynchronous with right ventricular pacing but synchronous with right atrial pacing. In dyssynchronous failing hearts, the lateral LV endocardium displayed a 2-fold increase in phosphorylated erk mitogen-activated protein kinase expression (with no change in phospho-p38 or phospho-jnk), a 30% decline in sarcoplasmic reticulum Ca 2ϩ -ATPase, an 80% reduction in phospholamban, and a 60% reduction in the gap junction protein connexin43, relative to neighboring myocardial segments. In contrast, hearts from both right atrial-paced HF dogs and an additional 4 noninstrumented control animals showed minimal regional variability in protein expression. Conclusions-LV dyssynchrony in failing hearts generates myocardial protein dysregulation concentrated in the late-activated, high-stress lateral endocardium. Such molecular polarization within the LV creates transmural and transchamber expression gradients of calcium handling and gap junction proteins that may worsen chamber function and arrhythmia susceptibility. Key Words: heart failure Ⅲ pacing Ⅲ molecular biology Ⅲ sarcoplasmic reticulum T he pathophysiology of heart failure (HF) involves abnormalities of stress response kinase signaling, neurohumoral stimulation, excitation-contraction coupling, gap junction and ion channel function, and chamber remodeling. 1,2 In addition, recent studies have shown that left ventricular (LV) mechanical coordination is frequently disturbed in HF, particularly in the setting of interventricular conduction delay. HF patients with interventricular conduction delay and concomitant ventricular dyssynchrony have mortality and sudden cardiac death rates above those predicted from the apparent severity of systolic dysfunction, HF etiology, functional class, or concurrent medical therapy. 3,4 Acute mechanical discoordination induced by single-site right ventricular (RV) or LV pacing depresses systolic function, worsens myocardial efficiency, and leads to marked increases in wall stress heterogeneity. 5,6 Stress is highest in late-activated myocardial regions because of both exaggerated stretch in early systole (secondary to septal contraction) and late systolic contraction against increased afterload. Chronic discoordination leads to chamber remodeling of both early-and late-activated segments. 7 However, its effect on myocardial protein expression remains unknown. In the present study, we tested the hypothesis that stress...

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“…Electrical dyssynchrony may not adequately describe the degree of mechanical dyssynchrony present; and therefore, the QRS duration may not be the best predictor of patient response to CRT [10][11][12]. Efforts have been made to improve the selection of patients who might benefit from CRT by using imaging modalities to define cardiac dyssynchrony more precisely.…”

Section: Introductionmentioning

confidence: 99%

Repeatability and reproducibility of phase analysis of gated single-photon emission computed tomography myocardial perfusion imaging used to quantify cardiac dyssynchrony

Trimble¹,

Velázquez²,

Adams³

et al. 2008

Nuclear Medicine Communications

136

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Systolic Improvement and Mechanical Resynchronization Does Not Require Electrical Synchrony in the Dilated Failing Heart With Left Bundle-Branch Block

Cited by 430 publications

References 20 publications

Short-Term Effects of Right-Left Heart Sequential Cardiac Resynchronization in Patients With Heart Failure, Chronic Atrial Fibrillation, and Atrioventricular Nodal Block

Short-Term Effects of Right-Left Heart Sequential Cardiac Resynchronization in Patients With Heart Failure, Chronic Atrial Fibrillation, and Atrioventricular Nodal Block

Regional Alterations in Protein Expression in the Dyssynchronous Failing Heart

Repeatability and reproducibility of phase analysis of gated single-photon emission computed tomography myocardial perfusion imaging used to quantify cardiac dyssynchrony

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