Effects of Atrial Rate-adaptive Pacing on Exercise Capacity in Patients With Chronic Heart Failure Complicated by Chronotropic Incompetence

Chronotropic incompetence consists of an insufficient increase in heart rate during effort, and its presence is recognized as a common feature in patients with heart failure due to left ventricular systolic dysfunction, apparently suggesting a worse prognosis. Little is known about the possible benefits of its reversal in such patients.

The investigators working hypothesis is that the modulation of chronotropic response, as obtained by means of atrial rate-adaptive pacing may improve functional capacity in persons with chronic heart failure and chronotropic incompetence.

To explore this hypothesis,the investigators will enroll 20 patients with NYHA II/III heart failure, low left ventricular ejection fraction (<40%) and chronotropic incompetence (Maximal heart rate <80% of predicted value in a symptom-limited incremental test), who already underwent implantation of dual-chamber implantable defibrillator for prevention of sudden cardiac death. The study will have a randomized, double-blind, cross-over design.

The procedures, to be carried out at one month from each reprogramming (VVI backup pacing vs. AAI-R "active" pacing), will comprise: blood sampling for NT-proBNP, incremental symptom-limited cardiopulmonary exercise testing (CPX), constant-workload cardiopulmonary test (50% of max WR), quality-of-life questionnaire, 24-hour ECG monitoring.

The primary end-point will be peak oxygen consumption on CPX. Secondary end-points will include acute response to reprogramming, and data derived from constant-WR tests, Holter monitoring and QoL.

Study Overview

• Status: Unknown
• Conditions: Heart Failure; Exercise Tolerance
• Intervention / Treatment: Other: Rate-adaptive pacemaker programming; Other: VVI at 40 bpm

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Serafino Fazio, MD; Phone Number: +390817463737; Email: fazio@unina.it
• Study Contact Backup: Name: Guido Carlomagno, MD; Email: guido.carlomagno@yahoo.it

Study Locations

• Italy
  • Naples, Italy, 80100
    • Recruiting
    • Federico II University - Department of Internal Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• NYHA II/III chronic heart failure on optimal medical therapy
• Sinus Rhythm
• Left ventricular ejection fraction less than 40 %
• Chronotropic incompetence on maximal exercise testing (maximum heart rate < 80% of predicted value)
• Age 18-75
• carrier of dual chamber ICD device
• Informed Consent

Exclusion criteria:

• Unable to perform cardiopulmonary exercise testing (for any reason)
• Absolute contraindication to maximal exercise testing
• Moderate to severe anemia (Hb<10 g/dL)
• Diagnosis of Sick Sinus Syndrome or high-degree atrioventricular block
• recent hospitalization for acute decompensated heart failure (<1 month)
• recent acute coronary syndrome (<3 months)
• Active neoplastic disease
• Active myocarditis / endocarditis
• Acute decompensated heart failure during study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Rate adaptive; Patients will have their ICD programmed in a AAI-R mode, with peak atrial rate set at 85% of age-adjusted predicted maximal HR	Other: Rate-adaptive pacemaker programming; The ICD will be programmed in a AAI-R mode, with peak atrial stimulation rate set at 85% of maximal predicted heart rate, and ongoing protection VVI backup at 40 bpm
ACTIVE_COMPARATOR: Control; ICDs will be programmed in the usual VVI backup pacing mode at 40 bpm	Other: VVI at 40 bpm; ICDs will be programmed in VVI mode at 40 bpm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Peak Oxygen consumption on cardiopulmonary exercise testing	1 month

Secondary Outcome Measures

Outcome Measure	Time Frame
Peak Heart Rate on Cardiopulmonary exercise testing	1 month
Quality of life as assessed by Minnesota Living with Heart Failure and SF-36 Questionnaires	1 month
Heart Rate Variability on Holter Monitoring	1 month
Acute Change in Peak Oxygen Consumption after reprogrammation	1 hour
NT-proBNP levels	1 Month

Collaborators and Investigators

• Sponsor: Federico II University

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (ANTICIPATED): July 1, 2012
• Study Completion (ANTICIPATED): August 1, 2012

Study Registration Dates

• First Submitted: November 18, 2009
• First Submitted That Met QC Criteria: November 18, 2009
• First Posted (ESTIMATE): November 19, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): June 27, 2011
• Last Update Submitted That Met QC Criteria: June 24, 2011
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Keywords: heart failure; chronotropic incompetence; oxygen consumption; cardiac pacing; ventricular dysfunction; left, exercise tolerance; pacemaker programming
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CHRON-INC-09