What are the indications and treatment approach for cardiac resynchronization therapy (CRT) in patients with heart failure?

Cardiac Resynchronization Therapy in Heart Failure

Primary Indications

CRT is definitively indicated for heart failure patients with LVEF ≤35%, sinus rhythm, LBBB pattern with QRS ≥150 ms, and NYHA class II-IV symptoms on optimal medical therapy, as this combination provides the strongest mortality and morbidity reduction. 1

Class I Recommendations (Strongest Evidence)

NYHA Class II Patients:

• LVEF ≤35% 2, 1
• Sinus rhythm 2, 1
• LBBB morphology with QRS ≥150 ms 2, 1
• Optimal medical therapy for ≥3 months (or ≥40 days post-MI) 1
• This combination reduces death and heart failure hospitalization by 42% (HR: 0.58, p<0.00001) 1

NYHA Class III and Ambulatory Class IV Patients:

• Same criteria as Class II: LVEF ≤35%, sinus rhythm, LBBB with QRS ≥150 ms 2, 1
• Level of Evidence: A 2

Critical QRS and Morphology Requirements

QRS ≥150 ms shows clear benefit across all NYHA classes 1, 3:

• Patients with QRS ≥150 ms: 42% reduction in adverse events (HR: 0.58,95% CI: 0.50-0.68; P<0.00001) 3
• Patients with QRS <150 ms: No benefit (HR: 0.95% CI: 0.83-1.10; P=0.51) 3

LBBB morphology is essential 1:

• LBBB pattern: 36% reduction in adverse events (RR: 0.64) 1
• Right bundle branch block: No benefit (RR: 0.91, p=0.49) 1
• Nonspecific intraventricular conduction delay: No benefit (RR: 1.19, p=0.28) 1

Class IIa Recommendations (Should Be Considered)

Atrial Fibrillation Patients:

• LVEF ≤35%, NYHA class III-IV 2
• QRS ≥130 ms (note: higher threshold than sinus rhythm patients) 2
• Requires ≥95% biventricular pacing 2
• AV nodal ablation often necessary to achieve adequate pacing percentage 2
• Registry data shows survival benefit equal to sinus rhythm patients only when AV ablation performed shortly after CRT implantation 2

Pacing-Dependent Patients:

• LVEF ≤35% with anticipated ≥40% ventricular pacing requirement 1
• Prevents pacing-induced cardiomyopathy 1
• Includes patients undergoing new or replacement device placement 1

Conventional Pacemaker Indication:

• NYHA class III-IV, LVEF ≤35%, QRS ≥120 ms 2
• Consider upgrading existing right ventricular pacemaker patients with severe ventricular dysfunction and NYHA class III symptoms 2

Class IIb Recommendations (May Be Considered)

NYHA Class I Patients:

• LVEF ≤30%, ischemic etiology 1
• Sinus rhythm, LBBB with QRS ≥150 ms 1
• On optimal medical therapy 1
• May prevent disease progression in early-stage heart failure 1

Mandatory Prerequisites Before CRT

1. Optimal medical therapy for ≥3 months (or ≥40 days post-MI if applicable) 1
2. Documented LVEF ≤35% on echocardiography 1
3. Life expectancy >1 year with acceptable functional capacity 1
4. 12-lead ECG confirming QRS duration and morphology 2, 1

Device Selection: CRT-P vs CRT-D

CRT-D (with defibrillator) is preferred when:

• Patient meets ICD criteria for primary or secondary prevention 2
• Reasonable expectation of survival with good functional status for >1 year 2
• NYHA class II patients (CRT preferentially by CRT-D) 2

CRT-P (pacemaker only) may be considered when:

• Patient does not meet ICD criteria 2
• Advanced age or significant comorbidities limiting life expectancy 2
• Patient preference after informed discussion 2

Populations Where CRT Should NOT Be Used

Narrow QRS Complex (<120 ms):

• Multiple trials (RethinQ, ESTEEM-CRT, LESSER-EARTH) showed no benefit or potential harm 2
• LESSER-EARTH trial was prematurely terminated due to futility and safety concerns 2
• Significant reduction in 6-minute walk distance and trend toward increased heart failure hospitalization 2

Non-LBBB Morphology with QRS <150 ms:

• No mortality or morbidity benefit demonstrated 1
• Consider only if QRS ≥150 ms regardless of morphology 2

Common Pitfalls and Caveats

Atrial Fibrillation Management:

• Pharmacologic rate control alone is often inadequate 2
• Monitor biventricular pacing percentage—must achieve ≥95% capture 2
• Consider AV nodal ablation early if <95% biventricular pacing achieved 2

QRS Duration Measurement:

• Must be measured on 12-lead ECG, not device interrogation 2
• Ensure proper lead placement and calibration 2

Mechanical Dyssynchrony Assessment:

• Echocardiographic dyssynchrony parameters should not replace electrical criteria (QRS duration/morphology) 2
• Trials using mechanical dyssynchrony as primary selection criteria failed to show benefit 2

Implantation Complications:

• Unsuccessful implantation in 8% of patients 4
• Risk of coronary sinus perforation requiring pericardiocentesis 4
• Refractory hypotension, bradycardia, or asystole in rare cases 4

Expected Clinical Outcomes

Symptomatic Improvement:

• Improvement in NYHA functional class (P<0.001) 4
• Increased 6-minute walk distance (+39 m vs +10 m, P=0.005) 4
• Improved quality of life scores (-18.0 vs -9.0 points, P=0.001) 4
• Increased exercise time (+81 vs +19 sec, P=0.001) 4

Cardiac Function:

• Improved ejection fraction (+4.6% vs -0.2%, P<0.001) 4
• LV reverse remodeling (≥15% reduction in end-systolic volume) 5

Morbidity and Mortality:

• Reduced hospitalization for heart failure (8% vs 15%, P<0.05) 4
• Reduced need for intravenous heart failure medications (7% vs 15%, P<0.05) 4
• 42% reduction in death or heart failure hospitalization in optimal candidates 1, 3

Response Rate:

• 60-70% of patients respond to CRT 5
• Non-responders more common with non-LBBB morphology, extensive myocardial scar, or suboptimal lead positioning 5