Physiologic pacing (also known as cardiac resynchronization therapy or CRT) refers to any form of cardiac pacing intended to restore or preserve synchronous ventricular contraction in patients with heart failure.
It can be achieved through biventricular pacing (using right ventricular and coronary sinus leads) or conduction system pacing (CSP), which includes His bundle pacing or left bundle branch area pacing.
Physiologic pacing is indicated for patients with heart failure with reduced ejection fraction (LVEF ≤50%) and either a high ventricular pacing burden (≥20-40%) or a wide QRS complex (particularly left bundle branch block with QRS ≥150 msec).
Guidelines recommend considering cardiac physiologic pacing for patients expected to require substantial ventricular pacing to reduce the risk of pacing-induced cardiomyopathy.
For patients with LVEF ≤35% on optimal guideline-directed medical therapy for ≥3 months, biventricular pacing has demonstrated improvements in mortality, heart failure hospitalization, quality of life, and left ventricular function in multiple randomized trials involving over 10,000 patients.
Biventricular pacing remains the gold standard with the strongest evidence base.
The BLOCK HF trial demonstrated that among 691 patients with LVEF ≤50% and atrioventricular block, biventricular pacing significantly reduced the composite outcome of death, urgent heart failure visits, or increase in left ventricular end-systolic volume compared to right ventricular-only pacing.
Benefits are greatest in patients with left bundle branch block and QRS duration ≥150 msec.
Conduction system pacing targets the His bundle or left bundle branch to engage the heart’s intrinsic conduction system, offering a more physiologic activation pattern.
Left bundle branch pacing has become the dominant conduction system pacing (CSP) approach due to higher success rates (92.4% in bradycardia, 82.2% in heart failure) and more stable pacing thresholds compared to His bundle pacing.
The evidence comparing CSP to biventricular pacing shows conflicting results.
Meta-analyses of predominantly observational studies suggest CSP may provide superior outcomes, with one analysis showing significant reductions in all-cause mortality and heart failure hospitalization,along with greater LVEF improvement.
Another meta-analysis of randomized trials found CSP resulted in greater QRS narrowing, LVEF improvement, and NYHA class reduction compared to biventricular pacing.
However, the PhysioSync-HF trial (2026) challenges these findings.
This randomized trial of 173 patients with HFrEF and left bundle branch block found CSP was inferior to biventricular pacing for the hierarchical composite of death, heart failure hospitalizations, urgent visits, and LVEF change at 12 months.
All-cause mortality was higher with CSP (HR 3.36), and LVEF improvement was less (8% vs 12% with biventricular pacing).
Biventricular pacing remains the first-line approach for most patients with standard CRT indications, particularly those with left bundle branch block and severely reduced LVEF.
CSP may be considered for failed coronary sinus lead placement, CRT nonresponders, or patients with unfavorable coronary sinus anatomy.