Cardiac Resynchronization Therapy (CRT)

Indications, Mechanisms, and Clinical Decision-Making

In patients with left ventricular (LV) systolic dysfunction and ventricular dyssynchrony, the normal mechanics of cardiac contraction are disrupted. Instead of contracting in a coordinated manner, different regions of the heart activate at different times, leading to inefficient pumping. Cardiac resynchronization therapy (CRT) is a specialized form of cardiac pacing designed to correct this abnormal timing by restoring coordinated (synchronous) ventricular activation.

CRT achieves resynchronization by delivering electrical stimulation to:

• Both ventricles simultaneously or nearly simultaneously (biventricular pacing), or
• The LV alone, or
• The native conduction system (conduction system pacing via the His bundle or left bundle area).

CRT has become a cornerstone of treatment for selected patients with heart failure with reduced ejection fraction (HFrEF), alongside optimal medical therapy and other device-based treatments.

Many patients eligible for CRT also meet criteria for implantable cardioverter-defibrillators (ICDs). While CRT focuses on improving cardiac mechanics and symptoms, ICDs primarily reduce the risk of sudden cardiac death; these indications often overlap but are evaluated separately.

Effects of Ventricular Dyssynchrony and Resynchronization Pathophysiology of Dyssynchrony In cardiomyopathy, electrical conduction delays—most commonly left bundle branch block (LBBB)—cause:

• Delayed activation of the basal posterolateral LV wall
• Inefficient and discoordinated LV contraction
• Reduced cardiac output
• Worsening functional mitral regurgitation
• Progressive adverse LV remodeling, including dilation

Dyssynchrony can occur:

• Within the LV (intraventricular dyssynchrony), and
• Between the LV and RV (interventricular dyssynchrony)

Observational studies consistently show that patients with LBBB have more severe heart failure symptoms and worse prognosis than those without significant conduction delay.

Hemodynamic and Structural Benefits of CRT By restoring coordinated ventricular activation, CRT can improve both acute hemodynamics and long-term cardiac structure and function. Acute effects may include:

• Increased systolic blood pressure
• Increased cardiac output
• Improved myocardial contractility Importantly, these benefits occur without a significant increase in myocardial oxygen consumption.

Chronic benefits include:

• Reverse LV remodeling (reduction in LV size and volumes)
• Improved LV ejection fraction (LVEF)
• Improved exercise tolerance and quality of life
• Reduced heart failure hospitalizations
• Reduced mortality in selected populations

Evidence from Key Clinical Trials CARE-HF trial

• LVEF increased by ~3.7% at 3 months and ~6.9% at 18 months
• LV end-systolic volume index decreased by ~30% at 18 months

MIRACLE trial

• At 6 months, LVEF increased by 3.6% with CRT versus 0.4% in controls
• LV end-systolic volume decreased significantly only in the CRT group

Across studies, greater reverse remodeling is associated with better survival, highlighting the mechanistic importance of resynchronization.

General Clinical Approach to CRT 1. Identify and Treat Reversible Causes of LV Dysfunction Before considering CRT, potentially reversible contributors to systolic dysfunction should be addressed, such as:

• Ischemia
• Valvular disease (eg, aortic regurgitation)
• Tachyarrhythmia-induced cardiomyopathy
• Toxin- or drug-related cardiomyopathy
• Endocrine disorders (eg, hyperthyroidism)

CRT should be considered only after these causes have been corrected or excluded.

2. Implement Optimal Guideline-Directed Medical Therapy Patients with LVEF ≤35% should receive maximally tolerated, evidence-based pharmacologic therapy for HFrEF, including agents that improve survival and reduce hospitalizations. The duration of medical therapy prior to CRT is individualized. In some patients—particularly those with:

• Established LBBB, or
• A need for another cardiac device (pacemaker or ICD)

Early CRT implantation may be reasonable, as improvement with medical therapy alone is unlikely.

3. Reassess Symptoms and Cardiac Function After optimization of medical therapy:

• Symptoms are reassessed (eg, NYHA functional class)
• LVEF is remeasured by echocardiography
• A repeat ECG is obtained to evaluate: - Rhythm - QRS duration - QRS morphology (eg, LBBB vs non-LBBB)

4. Determine Whether CRT Is Indicated The decision to proceed with CRT is based on a combination of:

• Symptom severity
• LVEF
• QRS duration
• QRS pattern (LBBB vs non-LBBB)
• Etiology of cardiomyopathy

Advanced imaging (eg, cardiac MRI) is not routinely required for CRT decision-making.

Contraindications and Special Considerations Relative Contraindications

• CRT may offer limited benefit or higher risk in patients with:
• Limited life expectancy (<1 year) due to noncardiac comorbidities
• Severe chronic obstructive pulmonary disease, where dyspnea is not primarily cardiac
• Advanced chronic kidney disease, especially in dialysis patients, due to: - Higher infection risk - Limited survival benefit
• Advanced age, which does not preclude CRT but requires careful risk–benefit counseling

CRT system upgrade (from pacemaker or ICD) is often beneficial but carries a higher complication risk than de novo implantation.

Absolute Contraindications CRT should generally not be performed in patients with:

• Active systemic infection
• Inability to tolerate anesthesia
• Inability to participate in device follow-up
• Stage D heart failure, including: - Inotrope-dependent patients - Nonambulatory class IV symptoms despite optimal therapy - Patients expected to undergo LV assist device implantation

Shared Decision-Making CRT is not a cure for heart failure, but for appropriately selected patients it can:

• Improve symptoms
• Reduce hospitalizations
• Prolong survival However:
• Approximately one-third of patients do not respond meaningfully
• A small subset may worsen (“negative responders”)

Predicting individual response remains challenging. Factors associated with better outcomes include:

• Nonischemic cardiomyopathy
• LBBB morphology
• High percentage of effective biventricular or LV pacing
• Female sex

The decision to pursue CRT should therefore be made through shared decision-making, integrating:

• Clinical evidence
• Procedural risks
• Patient values, preferences, and goals of care

KIMSHEALTH Perspective At KIMSHEALTH, CRT evaluation and implantation are guided by a multidisciplinary heart failure and electrophysiology team, ensuring:

• Careful patient selection
• Integration with optimal medical therapy
• Advanced pacing strategies, including conduction system pacing when appropriate

If you have heart failure with reduced ejection fraction, a widened QRS complex, or persistent symptoms despite medical therapy, consult the KIMSHEALTH Cardiology Team to determine whether cardiac resynchronization therapy could improve your heart function and quality of life.