Heart Rate Control in ICD Patients With Heart Failure Clinical Trial
Official title:
Effect of Heart Rate Control Using Ivabradine and Beta-blockers Combination Versus Beta-blockers Up-titration on Ventricular Pacing in Heart Failure Patients With an Implanted Cardioverter Defibrillator.
The aim of this prospective, randomized and controlled trial is to evaluate the use of the
ivabradine in combination to a low-dose of beta-blocker (bisoprolol) versus up-titration of
beta-blocker (bisoprolol) to obtain heart rate (HR) control with reduction in RV pacing in
single-chamber or dual chambers ICD recipients HF patients with moderate to severe left
ventricular dysfunction (FE ≤ 40%) and an heart rate ≥ 70 bpm in sinus rhythm over a
12-months follow up.
Besides the investigators want to assess if the combination of ivabradine to a low-dose of
beta-blocker (bisoprolol) versus up-titration of beta-blocker (bisoprolol) may determine a
lower degree of left ventricular dysfunction progression, the reduction of ventricular
arrhythmias burden and ICD appropriate therapy occurrence and the improvement of quality of
life in ICD heart failure patients.
Background
High heart rate (HR) represent per se a risk factor for cardiovascular mortality and heart
failure (HF) progression, despite optimal HF therapy. Beta-blockers remain the therapy of
choice in all patients with systolic HF, but they may worsen atrioventricular (AV) conduction
and increase right ventricular (RV) pacing percentage. Several studies have demonstrated
detrimental effects of RV pacing on cardiac function. Percent RV pacing > 40-50% is an
independent predictor of death and hospitalization for HF in implantable
cardioverter-defibrillator(ICD) patients, particularly in those with preexistent left
ventricular dysfunction.1,2 Cumulative RV pacing > 2% and ejection fraction (EF) < 40% are
independent predictors for Ventricular Tachycardia(VT)/Ventricular Fibrillation (VF)
occurrence in ICD patients.3 Therefore reduction of cumulative RV pacing as far as possible
should be achieved in ICD patients. Ivabradine is a specific inhibitor of the If current of
the sinus node, that induces a selective and dose dependent HR reduction; it is a pure HR
lowering agent without effects on AV conduction or contractility.4 In HF patients implanted
with an ICD ivabradine could act as an heart rate control drug in combination with a
beta-blocker without increase right ventricular (RV) pacing percentage and may be an option
to reduce left-ventricular dysfunction progression and ventricular arrhythmias burden and
appropriate ICD therapy.
Aim
The aim of this prospective, randomized and controlled trial is to evaluate the use of the
ivabradine in combination to a low-dose of beta-blocker (bisoprolol) versus up-titration of
beta-blocker (bisoprolol) to obtain heart rate (HR) control with reduction in RV pacing in
single-chamber or dual chambers ICD recipients HF patients with moderate to severe left
ventricular dysfunction (FE ≤ 40%) and an heart rate ≥70 bpm in sinus rhythm over a 12-months
follow up.
Besides we want to assess if the combination of ivabradine to a low-dose of beta-blocker
(bisoprolol) versus titration of beta-blocker (bisoprolol) may determine a lower degree of
left ventricular dysfunction progression, the reduction of ventricular arrhythmias burden and
ICD appropriate therapy occurrence and the improvement of quality of life in ICD heart
failure patients.
Endpoints of the study
Primary endpoints:
Right ventricular pacing percentage increase > 50% or Cardiovascular death or Heart failure
decompensation or Crossover due to worsening heart failure.
Secondary endpoints:
Ejection fraction decrease < 5% and Left Ventricular End-Systolic Volume decrease <15%.
Ventricular arrhythmias and ICD appropriate therapy reduction. Heart rate variability
improvement NYHA Classification improvement Minnesota Living With Heart Failure Questionnaire
(MLHFQ) total score reduction.
Right ventricular pacing percentage. Composite endpoint: cardiovascular death and
hospitalization due to worsening heart failure.
Crossover rate due to worsening heart failure
Study protocol:
Baseline assessment:
Clinical visit: demographic data, risk factors for cardiovascular disease, primary cause of
heart failure, NYHA class, comorbidities, echocardiographic parameters, drug therapy,
cardiovascular hospitalizations in the last year.
Rest ECG (for assessment of rest heart rate, presence of sinus rhythm or device-induced
rhythm, QRS duration); Blood pressure measurement; Electronic device control (for assessment
of right ventricular stimulation percentage; electrical parameters and arrhythmias diagnostic
data); Echocardiogram (for assessment of left ventricular end-diastolic and end-systolic
volumes, left ventricular ejection fraction); MLHFQ
Assignment of consecutive patients to treatment with ivabradine plus beta-blocker(bisoprolol)
or beta-blocker (bisoprolol) titration. Mean Heart Rate Target is 55-70 bpm for both groups.
Ivabradine will be administered at a dose of 5 mg twice daily in addition to a low dose of
beta-blocker (bisoprolol 1,25 or 2,5 mg). After four weeks of treatment ivabradine will be
eventually lowered up to 2,5 mg twice daily in the presence of side effects (phosphenes,
diplopia, headache or dizziness).
Beta blocker Bisoprolol will be up-titrated biweekly starting from the initial dose of
1,25-2,5 mg daily up to the max dose of 10 mg daily or to the maximum tolerated dose.
Patients are controlled in office follow-up visits after 3, 6 and 12 months, in addition to a
Remote Monitoring program for clinical data and trend reviewing at least every 15 days or as
soon as possible whenever a Remote Monitoring alert notification is received. Besides every
15 days patients will receive a telephone contact in order to evaluate their clinical state
and to uptitrate the beta blocker therapy based on mean heart rate detected trough remote
control of the ICD.
Three months in-office follow-up:
Clinical visit: symptoms, NYHA class, drug therapy, cardiovascular hospitalizations in the
last three months.
Rest ECG (for assessment of rest heart rate, presence of sinus rhythm or device-induced
rhythm, QRS duration); Blood pressure measurement; Echocardiogram (for assessment of left
ventricular end-diastolic and end-systolic volumes, left ventricular ejection fraction);
Electronic device control (for assessment of right ventricular stimulation percentage;
electrical parameters and arrhythmias diagnostic data) .
Six months in office follow-up:
Clinical visit: NYHA class, comorbidities, echocardiographic parameters, drug therapy,
cardiovascular hospitalizations in the last three months.
Rest ECG (for assessment of rest heart rate, presence of sinus rhythm or device-induced
rhythm, QRS duration); Echocardiogram (for assessment of left ventricular end-diastolic and
end-systolic volumes, left ventricular ejection fraction); Electronic device control (for
assessment of right ventricular stimulation percentage; electrical parameters and arrhythmias
diagnostic data).
MLHFQ
One year in office follow-up:
Clinical visit: NYHA class, comorbidities, echocardiographic parameters, drug therapy,
cardiovascular hospitalizations in the last three months.
Rest ECG (for assessment of rest heart rate, presence of sinus rhythm or device-induced
rhythm, QRS duration); Electronic device control (for assessment of right ventricular
stimulation percentage; electrical parameters and arrhythmias diagnostic data).
Echocardiogram (for assessment of left ventricular end-diastolic and end-systolic volumes,
left ventricular ejection fraction); MLHFQ
;