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EchoCRT trial

 
Defining a new standard of care for HF patients with a narrow QRS and ventricular dyssynchrony:
the EchoCRT trial


Evaluating the benefits of Cardiac Resynchronization Therapy (CRT)
Large-scale randomized controlled clinical trials have demonstrated that cardiac resynchronization therapy (CRT) improves morbidity and mortality in patients with moderate-to-severe heart failure (HF) and a wide QRS complex (> 120 ms). 1,2,3,4) However, many HF patients with a narrow QRS complex (< 120 ms) are currently excluded from receiving CRT under today’s guidelines, 5,6) even though approximately 50% of these patients present with clear echocardiographic evidence of dyssynchrony and could, therefore, potentially benefit from CRT.

In the setting of HF, echocardiography has emerged as the preferred diagnostic tool in detecting mechanical dyssynchrony and predicting the likelihood of improved LV performance from CRT. 7,8) Several smaller CRT studies have investigated patients with narrow QRS; however, these studies did not provide conclusive evidence to determine the appropriate clinical treatment for this patient population.9,10,11) Therefore, the EchoCRT trial has been designed to define the new standard of care for HF patients with a narrow QRS and ventricular dyssynchrony.
Expanding research: CRT trials examining mild HF patients with narrower QRS
Published studies of symptomatic HF and reduced cardiac performance (NYHA III/IV) provide conflicting evidence about the benefits of CRT in patients presenting with a narrower QRS complex. Though somewhat arbitrary, previous resynchronization trials have established a ‘long QRS’ as a duration of more than 150 ms, while a ‘short QRS’ is considered to be a value less than 150 ms, yet greater than 120 ms 12) as recommended in current guidelines from the ESC, EHRA, ACC and AHA 5,6). Despite the common presence of mechanical dyssynchrony in HF patients with narrow QRS, a recent European CRT Survey 13) showed that nearly half of the patients who are evaluated for CRT eligibility were not even assessed for mechanical synchrony using readily-available diagnostic tools.

Recently published CRT trials in patients with milder HF (NYHA I/II) and less pronounced inter- and/or intra-ventricular conduction delays (e.g., inclusion of QRS durations of > 120/130 ms) have provided some new evidence of incremental benefit from CRT-D vs. ICD-only therapy.14,15)

However, the results of a small, multicenter pilot study in HF patients with narrow QRS 16) failed to demonstrate its primary endpoint of increased peak oxygen consumption (VO2 max) during exercise testing. A similar small, multicenter, unblinded, single-arm trial failed to demonstrate any benefit in VO2max , LVEF, or LVEDD over a period of 6 months.17) Due to inherent limitations as well as lack of power, these pilot studies do not provide the necessary evidence for making clinical treatment decisions in this patient population. More focused research is required to better assess patient response to, and eligibility for, cardiac resynchronization therapy, particularly in HF patients with narrow QRS and evidence of ventricular dysynchrony.

Defining a new standard of care: the EchoCRT trial

Echocardiography Guided Cardiac Resynchronization Therapy (EchoCRT) trial in patients with narrow QRS and ventricular dyssynchrony

The lack of definitive evidence presented in more recent small, exploratory trials of narrow QRS complex HF patients provided the impetus for the design of an adequately powered, long-term, event-driven, randomized controlled trial to investigate the impact of CRT on morbidity and mortality in the large group of HF patients presenting with narrow QRS and ventricular dyssynchrony.

The EchoCRT trial is a prospective, international, multicenter, double-blinded, randomized (1:1 ratio), parallel-group, controlled resynchronization trial assessing the clinically relevant primary endpoints of mortality and morbidity. EchoCRT is designed to evaluate the effects of CRT on morbidity and mortality in subjects with HF on stable, optimal medical therapy with impaired LV systolic dysfunction (LVEF < 35%), a narrow QRS complex (<130 ms), and echocardiographic evidence of ventricular dyssynchrony.

The study will be conducted at over 100 investigational sites worldwide, including Europe, Canada, Israel, and Australia. Approximately 40 investigational sites will be located in the United States. According to the sample size it is anticipated that over 1100 patients will be randomized and followed for a minimum of 12 months in order to reach the necessary number of endpoints. The estimated study completion date is December 2012.

EchoCRT has been designed to meet the highest standards of evidence based medicine. The EchoCRT trial is an investigator-driven, collaborative effort led by an executive steering committee of 11 internationally-renowned academic specialists in electrophysiology, HF and echocardiography, whose collective contributions help ensure an appropriate trial design and optimized care of this defined patient population.

Inclusion criteria
Key trial inclusion criteria are adult patients with an ICD indication, stable optimal medical treatment, NYHA III-IV within the past 3 months prior to enrollment and at baseline, narrow QRS <130 ms, LVEF ≤35% and a LVEDD ≥55 mm. In EchoCRT, ventricular dyssynchrony will be measured by echocardiographic evidence in a local echocardiography lab (peak systolic velocity delay >80 ms measured by colored Tissue Doppler Imaging or speckle-tracking radial strain anteroseptal-posterior wall delay of >130 ms) and confirmed by a core laboratory to standardize echocardiographic interpretation across all participating centers, one of the many important aspects of this trial.

Endpoints
EchoCRT is based on a primary combined efficacy endpoint of all-cause mortality or first hospitalization for worsening heart failure in subjects with a narrow QRS complex and echocardiographic evidence of ventricular dyssynchrony. The primary safety endpoint will evaluate the complication free rate of the CRT-D devices (BIOTRONIK Lumax HF-T) in the narrow QRS patient population at 6 months. Secondary endpoints will examine rate of HF hospitalization, change in NYHA classification and QoL at 6 months and all-cause mortality. EchoCRT is an event-driven trial powered to investigate the effects of CRT on mortality and morbidity in HF patients with QRS <130 ms and echocardiographic evidence of ventricular dyssynchrony compared with optimal medical therapy alone.

Further trial details
The EchoCRT Co-Chairs are Dr. J. Holzmeister and Prof. F. Ruschitzka (University Hospital in Zurich, Switzerland); Prof. W. Abraham is the US Principal Investigator (Ohio State University, Columbus, Ohio). To date, 50 active centers have already been enrolled in the EchoCRT trial in 14 countries. In addition, numerous selected research centers will be activated or prepare for trial enrollment in the near future.

A positive EchoCRT trial outcome could expand the life-saving benefits of CRT to a significant number of HF patients not currently eligible for CRT under today's therapy guidelines.
Further information about EchoCRT trial design and center participation may be found at http://clinicaltrials.gov/show/NCT00683696 .

Sources

1. Cazeau et al. N Engl J Med. 2001; 344: 873–880
2. Abraham et al., N Engl J Med. 2002; 346:1845-53
3. Bristow M, N Engl J Med. 2004; 350: 2140-2150
4. Cleland JG et al., N Engl J Med. 2005; 352:1539-1549
5. Dickstein K, et al., Eur Heart J 2008; 29: 2388-2442
6. Epstein AE et al., Circulation 2008 ; 117(21): e350-408
7. Yu CM, et al., J Am Coll Cardiol. 2006; 48:2251-2257
8. Bleeker GB, et al., J Am Coll Cardiol. 2006; 48:2243-2250
9. Bleeker GB et al., J Cardiovasc Electrophysiol 2004; 15(5): 544-549
10. Achilli A et al., J Am Coll Cardiol. 2003; 42: 2117-2124
11. Yu CM et al., Heart 2003; 89: 54-60
12. Auricchio et al., J Am Coll Cardiol. 2003; 42: 2109-2116
13. Dickstein K et al., Eur Heart J 2009; doi:10.1093/eurheartj/ehp359
14. Daubert et al., REVERSE trial, J Am Coll Cardiol. 2009; Nov 10;54(20):1837-46
15. Moss et al., MADIT-CRT trial, N Engl J Med. 2009; Oct 1;361(14):1329-38
16. Beshai JF, et al., N Engl J Med. 2007; 357: 2461-2471
17. Donahue, et al., Eur Heart J 2008; 29: Suppl. 732, Abstract 4359