The purpose of this pilot clinical trial is to evaluate whether a novel cardiac resynchronization strategy, called LOT-CRT, is more effective than standard physiological pacing alone (LBBAP) in patients with heart failure.

This is a randomized, single-center, crossover pilot study involving 10 patients. All participants will receive a specialized pacemaker (CRT-P) with leads implanted in two specific areas: the Left Bundle Branch Area (LBBAP) and the Coronary Sinus (CS).

Because of the crossover design, each patient will serve as their own control, receiving two different pacing configurations in a random order: Active Phase (LOT-CRT): Simultaneous pacing of the left bundle branch and the coronary sinus. Control Phase (LBBAP alone): Pacing only the left bundle branch area. Each treatment phase will last 6 months, for a total follow-up of 12 months per patient.

By testing both strategies in the same patient, this study will help clinicians identify the most effective way to restore heart synchrony and improve clinical outcomes in patients with advanced heart failure and conduction delays.

This is a single-center, randomized, crossover pilot clinical trial. Each patient will serve as their own control. Following the successful implantation of a device capable of stimulating the LBBAP and the coronary sinus, participants will be randomly assigned to one of two treatment sequences:

Sequence A: LOT-CRT (LBBAP + CS) for 6 months, followed by LBBAP alone Sequence B: LBBAP alone for 6 months, followed by LOT-CRT Each treatment phase will last 6 months, followed by an end-point evaluation and a crossover. Since the hemodynamic effect of electrical stimulation is immediate, no washout period is required between phases.

This study was designed as an exploratory pilot study; therefore, no formal sample size calculation was performed. The number of patients enrolled is considered adequate to assess the feasibility of the procedure, the safety of the crossover design, and to identify preliminary signals of clinical and electrical efficacy.

Inclusion Criteria:

1. Age ≥18 years
2. Standard CRT-P indications according to ESC 2021 (EF ≤50%, QRS ≥130 ms, sinus rhythm or controlled AF)
3. NYHA class II-IV
4. Coronary venous anatomy suitable for placement of a coronary sinus electrode.
5. Signed informed consent.
6. Successful implantation of electrodes in the coronary sinus and in the left bundle branch area (LBBAP)

Exclusion Criteria:

1. Concomitant indication for implantation of an implantable cardioverter-defibrillator (ICD) or CRT-D
2. Significant uncorrected valvular disease or scheduled or anticipated cardiac surgery during the study period.
3. Anatomical or technical contraindication for lead implantation in the coronary sinus or for lead implantation in the coronary sinus (such as sinus stenosis, coronary sinus branches unsuitable for cannulation, inability to advance and/or stabilize the lead, among others)
4. Persistent atrial fibrillation with uncontrolled rate
5. Comorbidities that may limit life expectancy to <1 year
6. Participation in another clinical trial that could confound the evaluation of results within the last 6 months.
7. Pregnancy or inadequate contraception

Individual participant data, appropriately anonymized, that support the reported results will be made available to qualified researchers for the purposes of scientific research or meta-analysis. Requests must be addressed to the Principal Investigator and include a formal proposal. All requests will be subject to approval by the institutional ethics committee. As this is a study with a small sample size (10 patients), the protocol strictly enforces confidentiality; therefore, prior approval is always required to share these data.

The data will be available from 6 months to 5 years following the publication of the main results.

The data will be available from 6 months to 5 years following the publication of the main results.

Requests must be addressed to the Principal Investigator and include a formal proposal. All requests will be subject to approval by the institutional ethics committee.

Since all patients will have both a coronary sinus electrode and a branch electrode (LBBAP) implanted, the study will be blinded only to the participants and to the investigators responsible for conducting the 6-minute walk test, the echocardiogram, and the NT-proBNP assessment. It will not be blinded to the electrophysiologists due to technical requirements. Additionally, outcome assessors and data analysts will also be blinded to the pacing mode (LBBAP or LOT - CRT). It will be blinded to the investigators and the patients. Outcome assessors and data analysts will also be blinded to the pacing mode (LBBAP or LOT - CRT).