What is the recommended treatment for patients with significant interventricular (IV) delay?

Treatment of Significant Interventricular Delay

Cardiac Resynchronization Therapy (CRT) is the recommended treatment for patients with significant interventricular delay, particularly those with left bundle branch block (LBBB), QRS duration ≥150 ms, left ventricular ejection fraction (LVEF) ≤35%, and NYHA class II-IV symptoms despite optimal medical therapy. 1

Patient Selection for CRT

Class I Recommendations (Strongest Evidence)

• CRT is indicated for patients with LVEF ≤35%, sinus rhythm, LBBB with QRS duration ≥150 ms, and NYHA class II, III, or ambulatory IV symptoms on guideline-directed medical therapy (GDMT) 2
• This recommendation is based on multiple clinical trials showing approximately 30% decrease in hospitalizations and 24-36% reduction in mortality with CRT 2

Class IIa Recommendations (Moderate Evidence)

• CRT can be useful for patients with LVEF ≤35%, sinus rhythm, LBBB with QRS duration 120-149 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT 2
• CRT can be useful for patients with LVEF ≤35%, sinus rhythm, non-LBBB pattern with QRS duration ≥150 ms, and NYHA class III/ambulatory class IV symptoms on GDMT 2
• CRT can be useful in patients with atrial fibrillation and LVEF ≤35% on GDMT if the patient requires ventricular pacing or meets other CRT criteria, and AV nodal ablation or pharmacologic rate control will allow near 100% ventricular pacing 2
• CRT can be useful for patients on GDMT with LVEF ≤35% who are undergoing new or replacement device placement with anticipated requirement for significant (>40%) ventricular pacing 2

Class IIb Recommendation (Weaker Evidence)

• CRT may be considered for patients with LVEF ≤30%, ischemic etiology of heart failure, sinus rhythm, LBBB with QRS duration ≥150 ms, and NYHA class I symptoms 2, 1

Optimization of CRT

Atrioventricular (AV) Delay Optimization

• Doppler echocardiography can be used to determine the optimal AV delay to maximize left ventricular filling 3
• Optimally programmed AV delay during CRT can maximize the response in left ventricular function 3

Interventricular (V-V) Timing Optimization

• Optimizing V-V timing to sequentially activate the ventricles has shown modest clinical benefit compared to simultaneous biventricular stimulation 4
• In a randomized controlled trial, NYHA functional class improved in 75% of patients with optimized V-V timing versus 58% with simultaneous stimulation (p=0.01) 4
• Longer baseline interventricular activation delay is associated with better clinical outcomes (reduced mortality and heart failure hospitalization) 5

Advanced CRT Approaches

Left Bundle Branch-Optimized CRT (LOT-CRT)

• Recent evidence suggests that CRT based on left bundle branch pacing combined with coronary sinus left ventricular pacing (LOT-CRT) may provide greater QRS duration reduction and clinical outcomes compared to conventional biventricular pacing in patients with intraventricular conduction delay 6
• LOT-CRT demonstrated higher left ventricular ejection fraction at 6,12,18, and 24 months of follow-up compared to biventricular CRT 6
• Adverse clinical outcomes including heart failure rehospitalization and mortality were lower in the LOT-CRT group during 24 months of follow-up (hazard ratio 0.33, p=0.035) 6

Mechanism of Benefit

• Prolonged interventricular and intraventricular conduction causes regional mechanical delay within the left ventricle that results in reduced ventricular systolic function, altered myocardial metabolism, functional mitral regurgitation, and adverse remodeling with ventricular dilatation 2
• CRT improves ventricular systolic function, reduces metabolic costs, ameliorates functional mitral regurgitation, and can induce favorable remodeling with reduction of cardiac chamber dimensions 2
• Functional improvements include increased exercise capacity (peak oxygen consumption increase of 1-2 mL/kg/min), increased 6-minute walking distance (50-70 meters), and reduced heart failure symptoms 2

Important Considerations and Potential Pitfalls

• QRS morphology matters: The benefit of CRT is greatest in patients with LBBB pattern compared to non-LBBB patterns 2, 1
• QRS duration is critical: Patients with QRS duration ≥150 ms show greater benefit than those with QRS duration 120-149 ms 2
• Response heterogeneity: Approximately two-thirds of patients randomized to CRT show clinical response compared to one-third in control groups 2
• Suboptimal lead placement and areas of myocardial fibrosis may contribute to poor response to CRT in some patients 2
• For patients with atrial fibrillation, AV nodal ablation may be necessary to ensure high percentage of biventricular capture 2
• The choice between CRT-Pacemaker and CRT-Defibrillator should be based on overall risk assessment 1