Biventricular Pacing in Children After Surgery for Congenital Heart Disease
Condition: Congenital Heart Disease (CHD)
MeSH terms: Heart Diseases; Heart Defects, Congenital
Study type: Interventional

Summary: 
      Surgery with cardiopulmonary bypass (CPB) for congenital heart disease (CHD) causes low
      cardiac index (CI). With the increasing success of surgery for CHD, mortality has decreased
      and emphasis has shifted to post-operative morbidity and recovery. Children with CHD
      undergoing surgery with CPB can experience well-characterized post-operative cardiac
      dysfunction. When severe, patients can develop clinically important low cardiac output
      syndrome (LCOS) and hemodynamic instability. Management of LCOS and hemodynamic compromise is
      primarily accomplished via intravenous durgs like milrinone, dopamine or dobutamine, which
      affect the strength of the heart's muscular contractions. These are used to maintain adequate
      blood pressure (BP) and CI. However, inotropic agents are potentially detrimental to
      myocardial function and may increase risk for post-operative arrhythmia and impair
      post-operative recovery by increasing oxygen demand and myocardial oxygen consumption (VO2).
      In combination with the increased VO2 associated with CPB-induced systemic inflammatory
      response patients can develop a critical mismatch between oxygen supply and demand,
      essentially the definition of LCOS. Therefore, therapies that improve CI and hemodynamic
      stability without increased VO2 are beneficial. This study will test whether BiVp, a
      specialized yet simple pacing technique, can improve post-operative CI and recovery in
      infants with electro-mechanical dyssynchrony (EMD) after CHD surgery. This study hypothesizes
      that Continuous BiVp increases the mean change in CI from baseline to 72 hours in infants
      with EMD following CHD surgery compared to standard care alone.
    

Detailed description: 
      In adults with heart failure with intrinsic or iatrogenic left bundle branch block (eg, RV
      pacing), and more recently in those with narrow QRS complex, pacing the heart with advanced
      pacing techniques from both the left and right ventricle (LV, RV) termed cardiac
      resynchronization therapy (CRT) improves resting systolic heart function and
      mechanoenergetics.1 In these patients, CRT has been shown to increase LV stroke volume,
      ejection fraction, and stroke work, resulting in an enhancement of LV myocardial efficiency,
      without an increase in oxidative metabolism and even a decrease in energy utilization.2-4
      Furthermore, oxygen consumption seems to be distributed more homogeneously during CRT.2
      Beyond increasing resting myocardial efficiency, CRT may increase metabolic reserve as judged
      by the increase in cardiac work in response to dobutamine.5 CRT has also been shown to
      restore homogeneous myocardial glucose metabolism, without a decrease in myocardial
      perfusion.6 These findings were mirrored by similar findings regarding the effects of CRT on
      myocardial perfusion. Resting myocardial blood perfusion was unaltered by CRT despite an
      increase in left ventricular function. However, the distribution pattern of resting
      myocardial blood perfusion became more homogeneous, while hyperemic myocardial blood
      perfusion and myocardial blood perfusion reserve were enhanced by CRT.7 In the long-term, CRT
      improves morbidity and mortality in adults with heart failure.8, 9

      Children have myocardial dysfunction and possibly mechanical dyssynchrony following
      cardiopulmonary bypass and cardiac surgery. A significant number of children with congenital
      heart disease have either interventricular conduction delay or right bundle branch block
      (RBBB). For example, RBBB may occur in patients after ventricular septal defect repair.
      Others children may develop iatrogenic bundle branch block while requiring ventricular pacing
      for rate control, hemodynamic improvement or atrioventricular block. When postoperative
      pacing is indicated, the current method used is to sense or pace the right atrium, depending
      on the indication, and to pace the right ventricle (univentricular pacing). However,
      conventional RV univentricular pacing may increase myocardial stress and oxygen utilization
      through inhomogeneous contraction,10 while long-term right ventricular (univentricular)
      pacing has been shown in some patients to have detrimental effects on left ventricular
      remodeling, left ventricular function and clinical outcomes.11-13 Beyond the potential for
      pacing related myocardial stress and oxygen consumption, the post-operative care of children
      with congenital heart disease necessitates the use of potent inotropic agents at the expense
      of increased myocardial oxygen consumption, unwanted effects in the vulnerable post-bypass
      myocardium.14-16 Preliminary data in children with congenital heart disease undergoing
      surgical repair have shown acute benefits of CRT as manifested by increased systolic blood
      pressure and improved cardiac output associated with a reduced QRS duration. These beneficial
      effects were obtained in children with both single and dual ventricular physiology.17-20 Pham
      et al showed improvement in cardiac index with biventricular pacing in children after heart
      surgery, but not with conventional atrioventricular pacing, suggesting that in patients
      needing pacing in the postoperative period, biventricular pacing is better than conventional
      pacing, a conclusion previously reached in adults in the setting of cardiomyopathy.21-23
      Despite these beneficial immediate hemodynamic effects, and despite preliminary data on the
      beneficial effects of CRT in children with congenital heart disease,24-26 it is not known
      whether a longer period of biventricular pacing in the post-operative period following
      surgery for congenital heart disease is beneficial and whether this intervention can lead to
      improved clinical outcomes such as reduction of the use of inotropes, time to extubation and
      length of admission to the critical care unit. To answer these questions, a prospective,
      randomized trial is needed. The current study would serve as a pilot study for a larger trial
      in the event of encouraging results.

      Hypothesis

      Biventricular pacing improves recovery after cardiac surgery with cardiopulmonary bypass in
      children with congenital heart disease.

      Objectives

      Study the effects of biventricular pacing on post-operative hemodynamics and clinical
      outcomes in children after surgery for congenital heart disease.

      Design

      Randomized, non-blinded, clinical intervention.
    

Intervention name(s): Biventricular pacing
Intervention type(s): Other
Intervention description(s): Randomization into one of 3 study arms for acute phase and for extended phase.
Measurement of baseline variables on arrival to CCU. Acute pacing protocol (order of pacing randomized):
Atrial sensing- right ventricular pacing 10 min.
5 min no pacing (washout).
Atrial sensing - biventricular pacing 10 min.
5 min no pacing (washout).
Intrinsic rhythm
5 min no pacing (washout). Start extended phase pacing according to randomization. Measure hemodynamic variables 10 min after start of pacing.
Measure hemodynamic variables 30 min after start of pacing. Pacing hiatus for 60 minutes at 24 hours with measurement of hemodynamics without pacing and after reinitiating pacing.
Stop pacing at 72 hours or after extubation, whichever comes first. For those patients who are extubated before 72 hours: measurements will be taken before extubation and one hour after extubation. Pacing will then be stopped.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: Congenital Heart Disease (CHD); Cardiopulmonary Bypass (CPB); Cardiac Index; Hemodynamics; Pediatrics