Biventricular stimulation improves right and left ventricular function after tetralogy of Fallot repair: Acute animal and clinical studies

Thambo, Jean-Benoît; Santos, Pierre Dos; Guillebon, Maxime De; Roubertie, François; Labrousse, Louis; Sacher, Frédéric; Iriart, Xavier; Lafitte, Stéphane; Ploux, Sylvain; Jaı̈s, Pierre; Roques, X.; Haı̈ssaguerre, Michel; Ritter, Philippe; Clémenty, Jacques; Narayan, Sanjiv M.; Bordachar, Pierre

doi:10.1016/j.hrthm.2009.11.019

Cited by 65 publications

(42 citation statements)

References 26 publications

(24 reference statements)

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“…In patients with rTOF, QRS duration exceeding 180 ms is considered a predictor of severe ventricular arrhythmias which was linked to RV dilatation 6 11. We have previously identified this QRS feature in our animal model 10 12. In the present study, we found significant conduction disturbances associated with RV-EDVi.…”

Section: Discussionsupporting

confidence: 66%

Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot

Benoist

Dubes

Roubertie

et al. 2016

Heart

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ObjectiveThe growing adult population with surgically corrected tetralogy of Fallot (TOF) is at risk of arrhythmias and sudden cardiac death. We sought to investigate the contribution of right ventricular (RV) structural and electrophysiological remodelling to arrhythmia generation in a preclinical animal model of repaired TOF (rTOF).Methods and resultsPigs mimicking rTOF underwent cardiac MRI functional characterisation and presented with pulmonary regurgitation, RV hypertrophy, dilatation and dysfunction compared with Sham-operated animals (Sham). Optical mapping of rTOF RV-perfused wedges revealed a significant prolongation of RV activation time with slower conduction velocities and regions of conduction slowing well beyond the surgical scar. A reduced protein expression and lateralisation of Connexin-43 were identified in rTOF RVs. A remodelling of extracellular matrix-related gene expression and an increase in collagen content that correlated with prolonged RV activation time were also found in these animals. RV action potential duration (APD) was prolonged in the epicardial anterior region at early and late repolarisation level, thus contributing to a greater APD heterogeneity and to altered transmural and anteroposterior APD gradients in rTOF RVs. APD remodelling involved changes in Kv4.3 and MiRP1 expression. Spontaneous arrhythmias were more frequent in rTOF wedges and more complex in the anterior than in the posterior RV.ConclusionSignificant remodelling of RV conduction and repolarisation properties was found in pigs with rTOF. This remodelling generates a proarrhythmic substrate likely to facilitate re-entries and to contribute to sudden cardiac death in patients with rTOF.

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Section: Discussionsupporting

confidence: 66%

Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot

Benoist

Dubes

Roubertie

et al. 2016

Heart

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“…[2][3][4][5][6][7] In children with tetralogy of Fallot and pulmonary regurgitation, diastolic dysfunction and right ventricular (RV) enlargement have been shown to correlate with QRS prolongation, and resynchronization of the right ventricle has been shown to improve hemodynamics. [8][9][10][11][12][13][14][15][16][17][18] Similarly, adults with pulmonary hypertension (PH) may develop right ventricular failure and are known to have mechanical dyssynchrony that correlates both with disease severity and mortality, but this has not been shown in children. 19,20 We hypothesized that pediatric PH patients have electrical and mechanical dyssynchrony, and that electrical and mechanical dyssynchrony correlate with disease severity.…”

mentioning

confidence: 99%

Electrical and mechanical dyssynchrony in pediatric pulmonary hypertension

Hill

Maxey

Rosenthal

et al. 2012

The Journal of Heart and Lung Transplantation

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“…Biventricular stimulation decreased QRSd and improved biventricular contractility at short-term followup. 66 Six months of biventricular CRT demonstrated improvement in exercise tolerance, NYHA functional class, ventricular synchrony, and LV EF. 65 Therefore, although biventricular stimulation may involve a more difficult implantation process, it allows more consistently homogeneous ventricular activation when resynchronization of the failing RV with isolated RV pacing is not feasible or if concomitant LV dysfunction is present.…”

Section: Crt For the Failing Rvmentioning

confidence: 91%

“…Thambo et al 65,66 evaluated short-and long-term effects of biventricular CRT in adult tetralogy of Fallot patients with RV dysfunction. Biventricular stimulation decreased QRSd and improved biventricular contractility at short-term followup.…”

Section: Crt For the Failing Rvmentioning

confidence: 99%

Cardiac Resynchronization Therapy for Pediatric Patients With Heart Failure and Congenital Heart Disease

Motonaga

Dubin

2014

Circulation

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1879C ardiac resynchronization therapy (CRT) is an effective treatment for adult patients with left ventricular (LV) failure. Large prospective, randomized, controlled trials have demonstrated that CRT results in improvement in cardiac function, LV reverse remodeling, decreased hospitalizations for heart failure (HF), improved quality of life, and decreased overall mortality.1-5 However, 30% of adult patients are nonresponders to CRT, spurring further evaluation of electromechanical dyssynchrony to determine optimal pacing sites and to improve CRT selection criteria for maximal response. 1,6 The positive response in adult HF prompted exploration of the use of CRT in pediatric HF patients. However, the effectiveness of CRT in the pediatric population is difficult to evaluate because of the complex anatomic substrates of congenital heart disease (CHD) and scar formation from multiple cardiac surgeries with a higher proportion of right bundle-branch block (RBBB) and right ventricular (RV) failure than in the adult population. The typical adult HF scenario of an LV ejection fraction (EF) ≤35% with a left bundle-branch block (LBBB) is uncommon in children; therefore, the adult selection criteria for CRT cannot be easily translated to pediatric patients. Furthermore, a small heterogeneous pediatric patient population hinders a systematic assessment of long-term benefit from CRT. Principles of CRTIn the normal heart, ventricular electrical activation spreads through the His-Purkinje system, which has unique rapid propagation properties and widespread distribution. This allows highly coordinated electrical activation between distant regions of both ventricles, resulting in highly synchronous mechanical contraction. Given the strong relationship between electrical excitation and mechanical contraction in the myocardium, it is not surprising that abnormal electrical activation results in abnormal mechanical contraction. 7,8 During a spontaneous or pacing-induced bundle-branch block, ventricular activation spreads primarily cell to cell through the surrounding myocardium, which can be up to 4 times slower than the specialized His-Purkinje system. 9,10 This results in asynchronous electrical activation and thus asynchronous mechanical contraction in which opposing regions of the ventricular wall become out of phase with each other. Energy generated by contraction of early activated regions is dissipated by relaxation of late-activated regions, leading to decreased energy efficiency, depressed pump function, and deleterious ventricular remodeling. 11-14Approximately 25% of adults with HF exhibit a LBBB with mechanical dyssynchrony. CRT has traditionally targeted this electrical and mechanical dyssynchrony with biventricular pacing.15 By simultaneously pacing both ventricles, CRT uniformly prolongs the time to maximum contraction in each ventricle as the activation wave fronts from both ventricles merge. 16,17 This results in a more coordinated contraction pattern, more homogeneous distribution of regional loading conditions ...

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Biventricular stimulation improves right and left ventricular function after tetralogy of Fallot repair: Acute animal and clinical studies

Cited by 65 publications

References 26 publications

Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot

Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot

Electrical and mechanical dyssynchrony in pediatric pulmonary hypertension

Cardiac Resynchronization Therapy for Pediatric Patients With Heart Failure and Congenital Heart Disease

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