Echocardiography Guided Cardiac Resynchronization Therapy - EchoCRT

Description:

A cardiac resynchronization therapy defibrillator (CRT-D) is currently indicated for patients with symptomatic systolic chronic heart failure (CHF) (New York Heart Association [NYHA] class III/IV, ejection fraction (EF) <35%) with a QRS duration on electrocardiogram (ECG) of ≥120 msec. Many patients with QRS duration <120 msec also show evidence of dyssynchrony, and it is unclear if CRT-D would be helpful in patients with narrow QRS and dyssynchrony on echo.

Contribution to the Literature: The EchoCRT trial showed that CRT-D implantation in patients with symptomatic systolic CHF and a narrow QRS (<130 msec) does not improve outcomes when compared with controls, despite evidence of dyssynchrony on echo, and despite persistent dyssynchrony being associated with adverse cardiovascular outcomes. This confirms findings from other smaller studies on this topic.

Study Design

  • Randomized
  • Parallel

Patient Populations:

  • Age ≥18 years
  • NYHA class III/IV
  • LVEF ≤35%
  • Standard indication for ICD
  • Stable medical therapy, per current guidelines
  • QRS duration on ECG <130 msec
  • LVEDD ≥55 mm
  • Echo evidence of LV dyssynchrony

    Number of enrollees: 809
    Duration of follow-up: 19.4 months (mean)
    Mean patient age: 58 years
    Percentage female: 28%
    EF: 27%
    NYHA class: II (2.5%) III (94%), IV (3.0%)

Exclusions:

  • Acute decompensated CHF
  • Intravenous inotropic agents
  • Atrial fibrillation within 1 month
  • Bradycardia requiring pacing

Primary Endpoints:

  • All-cause mortality or hospitalization for worsening CHF

Secondary Endpoints:

  • CHF hospitalization
  • Change in NYHA class at 6 months
  • Change in QOL (assessed by the Minnesota Living with Heart Failure questionnaire) at 6 months
  • All-cause mortality

Drug/Procedures Used:

Patients with symptomatic CHF and narrow QRS meeting study criteria were randomized to receive CRT-D turned on or off. The Biotronik Lumax HF-T CRT-D system was exclusively utilized; all patients received three leads (atrial, right ventricular [RV], LV). In the control arm, the CRT-D device essentially functioned as an implantable cardioverter-defibrillator (ICD). Efforts were made to maximize CRT in the CRT arm and to minimize RV pacing in the control arm.

Concomitant Medications:

Angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (95%), aldosterone antagonist (60%), and beta-blocker (97%)

Principal Findings:

A total of 809 patients were randomized, 404 to CRT and 405 to control. Baseline characteristics were fairly similar between the two arms. The median QRS duration was 106 msec. Approximately 54% had an ischemic cardiomyopathy, with a median EF of 27%, and the majority of patients (94%) had NYHA class III symptoms. The median LV end-diastolic diameter (LVEDD) was 66.4 mm. More than half of the enrolled patients had evidence of dyssynchrony on echo by both tissue Doppler and radial strain; about 25% had dyssynchrony on tissue Doppler only, and the rest on radial strain only.

The trial was stopped early due to futility with a potential for harm. The primary outcome (all-cause mortality or hospitalization for worsening CHF) was similar between the CRT and control arms (28.7% vs. 25.2%, hazard ratio [HR] 1.20, 95% confidence interval [CI] 0.92-1.57, p = 0.15). CHF hospitalization was also similar (24.5% vs. 22.2%, p = 0.25), but all-cause mortality was higher in the CRT arm (11.1% vs. 6.4%, p = 0.02). This appeared to be driven by cardiovascular causes (9.2% vs. 4.2%, p = 0.004). There were no differences in NYHA class or quality of life (QOL) scores between the two arms.

Impact of dyssynchrony on outcomes: Persistent dyssynchrony at 6 months was observed similarly in both groups (77%). Persistent dyssynchrony was associated with a significantly higher primary endpoint (HR 1.54, 95% CI 1.03-2.30, p = 0.03), and CHF hospitalization (HR 1.66, 95% CI 1.07-2.57, p = 0.02), but not total mortality (p = 0.38). Both longitudinal and radial dyssynchrony were associated with HF hospitalizations. Associations of persistent or worsening dyssynchrony with outcomes were similar in the CRT and control groups.

Interpretation:

The results of the EchoCRT trial indicate that CRT-D implantation in patients with symptomatic systolic CHF and a narrow QRS (<130 msec) does not improve outcomes when compared with controls, despite evidence of dyssynchrony on echo, and despite persistent dyssynchrony being associated with adverse cardiovascular outcomes. Concerningly, there also appears to be an excess of mortality in the CRT-D arm, driven mostly by cardiovascular mortality.

It is postulated that CRT would be helpful in patients with LV dyssynchrony by improving LVEF and functional status by minimizing regional LV delay caused by prolonged ventricular conduction, reducing mitral regurgitation and LV reverse remodeling, and normalizing neurohormonal factors. However, earlier smaller studies such as RethinQ had demonstrated no clinical benefit with CRT-D use in patients with a narrow QRS. EchoCRT is the largest randomized clinical trial on this topic, also powered for clinical outcomes, and conclusively suggests that CRT-D is not helpful in this patient population.

This also corresponds with an emerging body of evidence that non–left bundle branch block (LBBB) morphologies obtain less or no benefit when compared with patients with LBBB and a wider QRS complex; the optimal benefit appears to be in patients with LBBB and QRS duration ≥150 msec.

References:

Gorcsan J III, Sogaard P, Bax LL, et al. Association of Persistent or Worsened Echocardiographic Dyssynchrony With Unfavourable Clinical Outcomes in Heart Failure Patients With Narrow QRS Width: A Subgroup Analysis of the EchoCRT Trial. Eur Heart J 2015;Aug 30:[Epub ahead of print].

Presented by Dr. John Gorcsan at the European Society of Cardiology Congress, London, August 30, 2015.

Steffel J, Robertson M, Singh JP, et al. The effect of QRS duration on cardiac resynchronization therapy in patients with a narrow QRS complex: a subgroup analysis of the EchoCRT trial. Eur Heart J 2015;May 25:[Epub ahead of print].

Ruschitzka F, Abraham WT, Singh JP, et al., on behalf of the EchoCRT Study Group. Cardiac-resynchronization therapy in heart failure with a narrow QRS complex. N Engl J Med 2013;369:1395-1405.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Valvular Heart Disease, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Acute Heart Failure, Mitral Regurgitation

Keywords: Cardiac Pacing, Artificial, Quality of Life, Mitral Valve Insufficiency, Cardiomyopathies, Heart Failure, Bundle-Branch Block, Medical Futility, Electrocardiography, Ventricular Dysfunction, Left, Hospitalization, Defibrillators, Implantable, Cardiac Resynchronization Therapy, ESC Congress


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