Bifocal Right Ventricular PAcing in Right Bundle Branch blocK and Heart Failure With Reduced Ejection Fraction. The Study Tests the Superiority of Right Ventricular Bifocal Stimulation Over VVI Implantable Defibrillator in Right Bundle Branch Block and Heart Failure.
Bifocal Right Ventricular PAcing in Right Bundle Branch blocK and Heart Failure With Reduced Ejection Fraction. The Study Tests the Superiority of Right Ventricular Bifocal Stimulation Over VVI Implantable Defibrillator in Right Bundle Branch Block and Heart Failure.
RATIONALE:

 Cardiac resynchronization therapy (CRT) is known to improve cardiac performance and to reduce
 morbidity and mortality in reduced-ejection fraction heart failure (HFrEF) despite optimal
 medical therapy (OMT). Several studies have shown that patients with with left bundle branch
 block (LBBB) respond favourably to CRT, whereas there is less certainty about non-LBBB
 morphology.

 Specifically, whether patients with right bundle branch block (RBBB) and HFrEF benefit from
 CRT is unclear. Some studies suggest lack of favourable outcomes. It follows from this that
 VVI implantable defibrillator are implanted in most RBBB patients.On the other hand right
 ventricular bifocal stimulation could be useful as an alternative approach in patient with
 RBBB. It consists of two endocardial leads implanted in right ventricle. The first lead is
 implanted in His bundle area, and the second lead is in the right ventricle apex. In this way
 bifocal pacing could decrease the inter- and intraventricular delays, thus improving left
 ventricular hemodynamics. However no specifically randomized studies are designed to date.

 PURPOSE:

 To demonstrate the superiority of right ventricular bifocal stimulation over placebo (VVI
 implantable defibrillator) in RBBB and HFrEF despite OMT.

 DESIGN Multicenter prospective randomized, double blind cross-over study. MASKING
 Investigator responsible for device programming is masked from having knowledge about
 clinical, functional, and echocardiographic data. On the other hand echocardiographist is
 masked from having knowledge about stimulation mode. Patients are masked from having
 knowledge about their clinical, functional, and device data.

 POPULATION At least fifty patients would be enrolled. The enrollment period should be one
 year. Study overall duration should be two years.

 ELIGIBILITY CRITERIA RBBB and HFrEF (left ventricular ejection fraction ≤35%) in sinus
 rhythm, in NYHA class II-III or ambulatory IV despite OMT.

 EXCLUSION CRITERIA

 -Refusal or withdrawal of informed consent.Renal failure (glomerular filtration rate ≤ 60
 ml/min).Life expectancy < 12 months.Active neoplasm.Permanent atrial fibrillation.40 days
 following acute coronary syndrome.Atrio-ventricular block (from second degree AV
 block).Valvular heart disease with surgery indications.

 PROTOCOL Each patient undergoes baseline assessment. Pharmacological therapy,
 hospitalization,NYHA functional class, QRS complex informations, type of heart disease and
 comorbidities are collected. Quality of life (QOL) is defined by Minnesota Living with Heart
 Failure questionnaire. Functional capacity is assessed by 6MWT (optionally by cardiopulmonary
 exercise test). Trans-thoracic echocardiogram is performed, analyzing: left-ventricle
 diameters and volumes, left-ventricle ejection fraction (LVEF), left atrial diameter and
 area, TAPSE,valvulopathy,systolic pulmonary artery pressure. All patients undergo bifocal
 right ventricular resynchronization therapy: right atrial lead is implanted, whereas the
 first ventricular lead is placed in His bundle area, and the second ventricular lead in the
 right ventricle apex. Then the leads are connected to the respective channels of a CRT-D
 generator.After the implant, all devices are programmed in VVI mode. After the first 40±10
 days (first f-up) patients are 1:1 randomized to VVI mode 40 beats/minute (placebo arm) or
 bifocal DDD-mode 60 beats/minute (with VV delay 0 msec and optimal AV delay). After six
 months (second f-up) a clinical and instrumental assessment equal to baseline is performed,
 as well as devices electrical parameters control. Then arms cross-over is performed (from
 VVI-mode to bifocal DDD-mode and vice versa). At 12 months (end of follow-up) an evaluation
 equal to that performed at 6 months is assessed. Echocardiographic data are unravelled to the
 investigator responsible for device programming. In this way the stimulation mode able to
 determine the best clinical improved (VVI or bifocal DDD mode) is programmed and the study
 closes.

 PRIMARY ENDPOINT The main assumption is that bifocal stimulation can increase of at least 20%
 the distance walked during 6MWT in respect of baseline and VVI-mode.The primary endpoint is
 the distance walked (expressed by meters) during 6MWT, as assessed at baseline, 6-months
 follow-up and 12 months follow up. Specifically changes in 6MWT observed during bifocal
 DDD-mode compared to baseline and to VVI mode would be significative if there is an increase
 of at least 20%.

 SECONDARY ENDPOINT

 Secondary endpoint is bifocal stimulation therapy response, defined by at least one of the
 following criteria, evaluated at baseline, 6-months follow-up and 12 months-follow-up in
 comparison to baseline and VVI mode:

 NYHA functional class improvement; changes in 6MWT, defined by an increase in distance walked
 major or equal to 30%; LVEF improvement major or equal to 25%;Left ventricular telesystolic
 volume reduction major or equal to 15%
Inclusion Criteria:

 -  Patients with RBBB and HFrEF (defined by left ventricular ejection fraction ≤35%) in
 sinus rhythm, who remain in NYHA class II-III or ambulatory NYHA class IV despite OMT.

 Exclusion Criteria:

 -  Refusal or withdrawal of informed consent.

 -  Renal failure (defined by an estimated glomerular filtration rate ≤ 60 ml/min)

 -  Life expectancy < 12 months

 -  Active neoplasm

 -  Permanent atrial fibrillation

 -  40 days following acute coronary syndrome

 -  Atrio-ventricular block (from second degree AV block)

 -  Valvular heart disease with surgery indications