Clinical trial NCT02139891: Effects of Multipoint Pacing CRT-D on Neurohormonal Activation.
Official title: Randomized, Crossover Study of the Effects of MultiPoint Left Ventricular Pacing on Neurohormonal Activation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure
Keywords: Cardiac Resynchronization Therapy
non responders
MultiPoint Pacing (MPP)
Lead sponsor: University of Rome Tor Vergata
Sponsor class: OTHER
First posted: 2014-05-15
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This study will examine the additional clinical benefit conferred by multipoint pacing (MPP) compared to standard CRT over a period of 3 months. Patients will be randomized to MPP ON vs. OFF and followed for a total of 6 months. This includes two crossover periods for each pacing modality (MPP on vs. off).

Detailed description: Cardiac resynchronization therapy (CRT) is limited by a high proportion of non-responders. Pacing activation from multiple separated left ventricular (LV) sites might improve the depolarization pattern, thereby promoting more physiological activation. To explore the effect of MPP on cardiac neuro-hormonal activity, the investigators will enroll approximately 30 patients who already underwent CRT-D implantation with a quadripolar LV lead connected to a device capable of MPP.

This pilot study will have a randomized, double-blind, cross-over design. Patients will be randomized to receive either standard biventricular pacing (MPP-OFF) or MPP (MPP-ON) within 4-6 months following the implantation procedure. Each subject will crossover to the other study group after three months. The baseline evaluation should be acquired prior to the device being programmed to the randomized setting. Repeat evaluations will be performed at the end of each 3 month crossover period.

Participation in this study will last approximately 6 months. Patients, as well as investigators other than the EP physicians, will be blinded to the pacing mode.

Eligibility criteria: Inclusion Criteria:

* Patients implanted with a St. Jude Medical CRT-D system with MPP capability
* Patients must be willing and able to sign an appropriate informed consent form and comply with study requirements
* NT pro-BNP levels equal to or greater than 500 pg/ml.

Exclusion Criteria:

* History of stroke, PCI, myocardial infarction or unstable angina pectoris within the last 3 months.
* Atrial fibrillation with noncontrolled heart rate
* Need for intravenous inotropic support for CHF
* Classification of Status 1 for cardiac transplantation or consideration for transplantation over the next 12 months
* Undergone a cardiac transplantation
* Currently participating in any other clinical investigation
* Life expectancy \< 12 months due to a disorder other than CHF
* Inability to comply with the follow-up procedures
* Patients who are or may potentially be pregnant

Primary outcomes:
measure: Changes in blood concentrations of N-terminal pro-B type natriuretic peptide (NT pro-BNP)
timeFrame: Baseline. 3-Month. 6-Month.
Secondary outcomes:
measure: Changes in Neurohormonal Activation
timeFrame: Baseline. 3-Month. 6-Month.
measure: Heart Failure Hospitalizations
timeFrame: 3-Month. 6-Month.
measure: New York Heart Association (NYHA) Class changes
timeFrame: Baseline. 3-Month. 6-Month.
measure: Changes in Quality of Life (QOL), as assessed by the Minnesota Living With Heart Failure Questionnaire
timeFrame: Baseline. 3-Month. 6-Month.
measure: Echocardiographic changes
timeFrame: Baseline. 3-Month. 6-Month.
measure: Appropriate device interventions (anti-tachycardia pacing or shock)
timeFrame: 3-Month. 6-Month.
measure: Phrenic Nerve Complication Free Rate
timeFrame: 3-Month. 6-Month.
measure: Occurrence of atrial and ventricular arrhythmias (amount and duration [h/day]).
timeFrame: 3-Month. 6-Month.
measure: Flow-mediated vasodilation
timeFrame: Baseline. 3-month. 6-month
measure: Packer's clinical composite score
timeFrame: Baseline. 3-month. 6-month.
measure: 6-Minute-Walking-Distance
timeFrame: Baseline. 3 Month. 6 Month.
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Istituto Clinico St. Ambrogio
city: Rome
country: Italy
facility: Policlinico Tor Vergata
Study officials:
affiliation: University of Rome Tor Vergata
name: Giovanni B Forleo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pappone C, Calovic Z, Vicedomini G, Cuko A, McSpadden LC, Ryu K, Romano E, Saviano M, Baldi M, Pappone A, Ciaccio C, Giannelli L, Ionescu B, Petretta A, Vitale R, Fundaliotis A, Tavazzi L, Santinelli V. Multipoint left ventricular pacing improves acute hemodynamic response assessed with pressure-volume loops in cardiac resynchronization therapy patients. Heart Rhythm. 2014 Mar;11(3):394-401. doi: 10.1016/j.hrthm.2013.11.023. Epub 2013 Nov 28.
citation: Rinaldi CA, Leclercq C, Kranig W, Kacet S, Betts T, Bordachar P, Gutleben KJ, Shetty A, Donal E, Keel A, Ryu K, Farazi TG, Simon M, Naqvi TZ. Improvement in acute contractility and hemodynamics with multipoint pacing via a left ventricular quadripolar pacing lead. J Interv Card Electrophysiol. 2014 Jun;40(1):75-80. doi: 10.1007/s10840-014-9891-1. Epub 2014 Mar 14.