Optimal Pacing Rate for Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) after atrioventricular node (AVN) ablation for permanent atrial fibrillation (AF) has led to better outcomes in heart failure (HF) patients with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF) compared to pharmacotherapy. Emerging evidence has demonstrated patients with HFpEF may benefit from a higher heart rate compared to standard heart-lowering therapies. The optimal pacing rate for CRT after AVN ablation in persistent AF and HFpEF remains unknown.

This is a prospective, randomized crossover study. The objective of the study is to determine if a pacing rate of 80 beats per minute (bpm) improves exercise tolerance during the 6-minute walk test.

The investigators will randomly assign half of the participants to a starting rate of 60 bpm and then switch them to a rate of 80 bpm for 3 months, and vice versa. Patient mortality and HF hospitalizations will be recorded at each phase. An electrocardiogram, echocardiogram, pacemaker interrogation, BNP and creatinine levels, KCCQ-12, six-minute walk test, and physical activity measure will be obtained at baseline, 3 months, and 6 months.

Inclusion criteria

• Age 18 years or older
• History of persistent or permanent atrial fibrillation
• Implantation of CRT or conduction system pacing in prior 3 months to 5 years of study start
• History of intrinsic AVN block or have undergone AVN ablation in prior 3 months to 5 years of study start
• LVEF ≥ 50%
• N-terminal pro-B-type natriuretic peptide (NT-proBNP) >400 pg/mL in the last 24 months
• Clinical HF diagnosis or NYHA class II or higher
• Able to provide informed consent

Exclusion criteria

• LVEF <50%
• Wide QRS (greater than 150ms)
• Isolated RV pacing
• Severe valvular disease
• Severe coronary artery disease as defined by one of the following:

• ACS or PCI within 1 year
• Any angina (CCS class 1+)
• Unrevascularizable severe CAD (>70% stenosis in 1+ major vessels and/or based on functional assessment)
• ESRD
• Significant primary pulmonary disease on home oxygen
• Major orthopedic issues, such as being wheelchair bound and/or unable to perform a six-minute walk test
• Ventricular ectopy >15% premature ventricular contractions (PVC)
• End stage cancer diagnosis
• Life expectancy less than one year
• Palliative or hospice care
• Hypertrophic cardiomyopathy (HCM)
• Uncorrected ventricular septal defect
• Infiltrative cardiomyopathy (CM)
• Uncontrolled hypertension as defined by blood pressure >160/100 mm Hg on two measurements ≥15 minutes apart
• Hemoglobin <7 g/dL
• Age >90 years old
• Pregnant or intends to become pregnant