Clinical trial NCT02154750: AV Delay Optimization vs. Intrinsic Conduction in Pacemaker Patients With Long PR Intervals
Official title: Evaluation of AV Delay Optimization vs. Intrinsic Conduction in Patients With Long PR Intervals Receiving Dual Chamber Pacemakers for Symptomatic Bradycardia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Atrioventricular Block
Sick Sinus Syndrome
Symptomatic Bradycardia
Cardiac Arrhythmia
Keywords: Atrioventricular delay
AV delay
Pacemaker
Sick Sinus Syndrome
Bradycardia
PR interval
Atrioventricular block
AV block
Echocardiography
Arrhythmia
AV optimization
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2014-06-03
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, prospective clinical trial to determine the effects of two different pacemaker atrioventricular delay (AV delay) settings on heart function in patients with dual chamber pacemakers implanted for symptomatic bradycardia with long PR intervals (delayed conduction between upper and lower chambers of the heart). The study will compare a long, fixed AV delay (standard) with an optimized AV delay for each individual using echocardiography (experimental).

Detailed description: Cardiac pacing is the only effective treatment for symptomatic sinus node dysfunction. Most patients with preserved left ventricular function receive dual chamber pacemakers; however, right ventricular pacing can have detrimental effects on left ventricular function due to the abnormal electrical and mechanical activation pattern of the ventricles.

Many patients receiving dual chamber pacemakers for symptomatic bradycardia have prolonged intrinsic AV conduction (first degree AV block), and as a result, will receive a significant amount of ventricular pacing if programmed at physiologic AV intervals. As an alternative, many pacemakers can be programmed to minimize ventricular pacing at the expense of allowing longer AV delays. However, these long AV delays may not be physiologic and may also lead to reduced cardiac output. At present the standard of care is either to program the pacemaker at an physiologic "natural" AV delay of about 160 msec or to program the pacemaker with a long AV delay to minimize ventricular pacing.

The main scientific questions being addressed in this study are to evaluate the acute and chronic effects on cardiac output, functional status, sense of well-being, and cardiac remodeling of a long AV delay allowing for intrinsic conduction as compared to an echocardiographically optimized AV delay during dual chamber pacing.

Patients enrolled in the trial will complete a run-in period of two weeks prior to randomization in which pacemakers will be programmed with a long-fixed AV delay to allow intrinsic conduction and minimize ventricular pacing (standard). At two weeks, patients will receive a baseline echocardiogram. To determine optimal AV delay, all patients will undergo echocardiographic analysis at varying AV delays. Optimal AV delay will be defined as the AV delay associated with the largest average aortic Doppler velocity time integral (VTI). Then, patients will be randomized to either the short, optimized (experimental) or long, fixed (standard) AV delay groups. To assess functional status and sense of well-being, patients will complete a six minute walk test and Short Form-36 Medical Outcomes Study Questionnaire. Patients return to clinic for another study visit at 6 months and repeat research procedures, including baseline echocardiogram, questionnaire, and 6 minute walk test.

Eligibility criteria: Patient population: Individuals with 1st degree atrioventricular (AV) block who have received a dual chamber pacemaker for symptomatic bradycardia.

Inclusion Criteria:

1. Patients greater than 18 years of age
2. Patients with symptomatic sinus bradycardia
3. Patients who meet standard indications for dual chamber pacemaker implantation
4. Patients who have 1st degree AV block determined by PR interval \> 200ms

Exclusion Criteria:

1. Patients with complete or high grade AV block
2. Patients who are unable to complete dual chamber pacemaker implantation for any reason
3. Patients with congestive heart failure determined by a Left Ventricular Ejection Fraction \< 45%
4. Patients with persistent atrial fibrillation
5. Sustained premature ventricular contractions (PVCs), premature atrial contractions (PACs), atrial flutter, or other heart conditions that may interfere with echocardiography measurements
6. Patients who are pregnant
7. Patients with Paroxysmal Atrial Fibrillation that have had an episode(s) within 30 days of consent

Primary outcomes:
measure: Comparison of Change in Echocardiographic Parameters LV Dimension at End-diastole, LV Dimension at End-systole, and Tricuspid Annular Plane Systolic Excursion (cm) From Baseline to Followup, in Optimized AV Delay Versus Long-fixed AV Delay Groups.
timeFrame: 6 months
measure: Comparison of Echocardiographic Parameters Mitral E Wave Velocity (cm/s) and Mitral A Wave Velocity (cm/s) at Baseline and Followup, in Optimized AV Delay Versus Long-fixed AV Delay Group.
timeFrame: 6 months
measure: Comparison of Change in Echocardiographic Parameter ΔE/A and Mean E/e' Ratio (Unitless) From Baseline to Followup, in Optimized AV Delay Versus Long-fixed AV Delay Groups.
timeFrame: 6 months
measure: Comparison of Echocardiographic Parameter Deceleration Time (Msec) at Baseline and Followup, in Optimized AV Delay Versus Long-fixed AV Delay Group.
timeFrame: 6 months
measure: Comparison of Change in Echocardiographic Parameters LVED End Diastolic Volume Index, LVES Volume Index, Maximum LA Volume Index, and Minimum LA Volume Index (ml/m2) From Baseline to Follow-up, in Optimized AV Delay Versus Long-fixed AV Delay Groups.
timeFrame: 6 months
measure: Comparison of Change in Echocardiographic Parameters Left Ventricular Ejection Fraction and Global Longitudinal Strain (%) From Baseline to Followup, in Optimized AV Delay Versus Long-fixed AV Delay Groups.
timeFrame: 6 months
measure: Comparison of Change in Echocardiographic Parameters Tricuspid Regurgitation (TR) Velocity m/s From Baseline to Followup, in Optimized AV Delay Versus Long-fixed AV Delay Groups.
timeFrame: 6 months
measure: Comparison of Change in Echocardiographic Parameters Left Ventricular Mass (gm) From Baseline to Followup, in Optimized AV Delay Versus Long-fixed AV Delay Groups.
timeFrame: 6 months
Secondary outcomes:
measure: Comparison of Measured Distance Walked in 6 Minutes in Meters From Baseline and Followup, in Optimized AV Delay Group Versus Long-fixed AV Delay Group.
timeFrame: 6 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD Sulpizio Cardiovascular Center
state: California
Study officials:
affiliation: UCSD Electrophysiology
name: Gregory K Feld, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Tops LF, Schalij MJ, Bax JJ. The effects of right ventricular apical pacing on ventricular function and dyssynchrony implications for therapy. J Am Coll Cardiol. 2009 Aug 25;54(9):764-76. doi: 10.1016/j.jacc.2009.06.006.
citation: Iliev II, Yamachika S, Muta K, Hayano M, Ishimatsu T, Nakao K, Komiya N, Hirata T, Ueyama C, Yano K. Preserving normal ventricular activation versus atrioventricular delay optimization during pacing: the role of intrinsic atrioventricular conduction and pacing rate. Pacing Clin Electrophysiol. 2000 Jan;23(1):74-83. doi: 10.1111/j.1540-8159.2000.tb00652.x.
citation: Sweeney MO, Ellenbogen KA, Tang AS, Whellan D, Mortensen PT, Giraldi F, Sandler DA, Sherfesee L, Sheldon T; Managed Ventricular Pacing Versus VVI 40 Pacing Trial Investigators. Atrial pacing or ventricular backup-only pacing in implantable cardioverter-defibrillator patients. Heart Rhythm. 2010 Nov;7(11):1552-60. doi: 10.1016/j.hrthm.2010.05.038. Epub 2010 Jun 4.