What is Cardiac Resynchronization Therapy (CRT)?
Cardiac Resynchronization Therapy (CRT) is a device-based treatment that uses biventricular pacing to restore synchronized contraction between the right and left ventricles in heart failure patients with electrical conduction delays, thereby improving cardiac function, reducing mortality by 25-36%, and decreasing heart failure hospitalizations by 30-40%. 1, 2, 3
Mechanism of Action
CRT corrects ventricular dyssynchrony caused by bundle branch blocks, particularly left bundle branch block (LBBB), which creates temporal delays in ventricular activation. 3 The therapy works through:
- Three pacing leads that simultaneously stimulate both ventricles and the right atrium, eliminating the interventricular and intraventricular conduction delays that characterize electrical dyssynchrony 3
- Restoration of coordinated contraction between right and left ventricles, which improves the mechanical efficiency of cardiac pumping 1, 4
- Reduction in metabolic costs of cardiac contraction while increasing left ventricular ejection fraction by 5-10% 3
Physiologic Benefits
The therapy produces measurable improvements in cardiac structure and function:
- Reverse remodeling with reduction in left ventricular end-diastolic and end-systolic volumes 3, 1
- Decreased functional mitral regurgitation caused by temporal delays in ventricular activation 3
- Improved ventricular systolic function independent of baseline ejection fraction 1
Clinical Outcomes: Mortality and Morbidity
The evidence for CRT's impact on hard outcomes is robust and consistent across multiple landmark trials:
- 36% reduction in all-cause mortality in NYHA class III-IV patients compared to medical therapy alone 3
- 25% reduction in death from any cause (HR 0.75,95% CI 0.62-0.91, p=0.003) demonstrated in the RAFT trial 5
- 30-40% decrease in heart failure hospitalizations across multiple randomized controlled trials 3, 5
- 32% reduction in heart failure-related urgent care in patients requiring pacemakers (BLOCK-HF trial) 1
Who Benefits: The Ideal Candidate Profile
The strongest evidence supports CRT in patients with specific electrical and clinical characteristics:
- LVEF ≤35% on optimal medical therapy for ≥3 months 2
- Sinus rhythm (atrial fibrillation requires special considerations) 2
- LBBB pattern with QRS ≥150 ms - this combination shows 36% reduction in adverse events (RR 0.64) 2
- NYHA class II-IV symptoms on guideline-directed medical therapy 2, 3
Critical caveat: The QRS morphology matters profoundly. Patients with LBBB show clear benefit, while those with right bundle branch block show no benefit (RR 0.91, p=0.49) and nonspecific intraventricular conduction delay actually show harm (RR 1.19, p=0.28). 2 Multiple trials including RethinQ, ESTEEM-CRT, and LESSER-EARTH consistently demonstrated that CRT in patients with narrow QRS complex (<120 ms) is not beneficial and may increase mortality. 1
Device Options
CRT comes in two configurations:
- CRT-P (pacemaker only) for patients without indication for defibrillator 1
- CRT-D (with defibrillator) for patients meeting criteria for both resynchronization and sudden cardiac death prevention, which provides backup defibrillation to terminate ventricular arrhythmias 3
Expanding Indications Beyond Classic Criteria
Recent evidence has broadened CRT application:
- Mild symptoms (NYHA class I-II): The REVERSE, MADIT-CRT, and RAFT trials demonstrated significant reverse remodeling, reduced hospitalizations, and mortality reduction even in mildly symptomatic patients with wide QRS and LBBB 1
- Patients requiring pacemakers: The BLOCK-HF trial showed that biventricular pacing significantly reduces adverse outcomes by 26% compared to right ventricular pacing alone in patients with AV block, regardless of baseline LVEF 1
- Prevention of pacing-induced cardiomyopathy: CRT is recommended for patients with LVEF ≤35% undergoing device placement with anticipated ≥40% ventricular pacing requirement 2
The "Non-Response" Problem: A Flawed Concept
The reported non-responder rate of 20-40% reflects a fundamental misunderstanding of CRT's benefits. 1 The binary classification of "response" using arbitrary improvement thresholds underestimates the true disease-modifying effects demonstrated in randomized trials. 1 All major CRT trials show a spectrum of outcomes from disease stabilization to improvement to recovery, not a binary response/non-response pattern. 1
When apparent non-response occurs, systematic evaluation reveals correctable factors:
- Inadequate biventricular pacing percentage (<95% of heartbeats) due to atrial fibrillation or premature ventricular contractions 1
- Suboptimal lead positioning requiring repositioning 1
- Inadequate medical therapy optimization post-implant 1
- Wrong patient selection: underlying narrow QRS, RBBB, or non-specific intraventricular conduction delay where CRT provides no benefit 1, 2
Post-Implant Optimization
A protocol-driven multidisciplinary approach can improve outcomes in 50% of initial "non-responders": 1
- Device interrogation to verify >95% biventricular pacing 1
- ECG analysis to confirm appropriate pacing patterns 1
- Echocardiographic assessment of lead positioning and AV/VV interval optimization 1
- Arrhythmia management: AV nodal ablation or PVC ablation to achieve consistent biventricular capture 1
- Medical therapy uptitration after CRT implantation 1
Absolute Contraindications
CRT should not be used in:
- QRS duration <120 ms even with echocardiographic dyssynchrony (consistently shows harm in trials) 1, 3
- NYHA class IV with refractory symptoms requiring continuous intravenous inotropes 3
- Life expectancy <1 year due to non-cardiac comorbidities 2, 3
The Underutilization Crisis
Despite robust evidence and cost-effectiveness, only one in three eligible patients actually receives CRT in Europe. 1 This "failure to refer" represents a significant gap between evidence and practice, depriving many heart failure patients of a therapy that reduces mortality by 25-36% and substantially improves quality of life. 1, 3