Authors

Tang A, Wells GA, Talajic M, et al

Title

Cardiac Resynchonization Therapy for Mild-to-Moderate Heart Failure

References

N Engl J Med 2010;363:2385-95

Background

Previous trials had demonstrated that ICDs improve survival in patients with HF, LV dysfunction and NYHA class II or III symptoms on optimal medical therapy. Improvement with symptoms and quality of life has been demonstrated with cardiac-resynchronization therapy (CRT) in advanced HF patients with a wide QRS.

Purpose

To determine if the addition of CRT to optimal medication therapy and an ICD would decrease rates of hospitalization and death for patients with mild-to-moderate heart failure and a wide QRS as compared to optimal medication therapy and an ICD alone.

Design

Multicenter, randomized, double-blinded, controlled trial
1798 adult patients with NYHA class II or III, LVEF ≤30%, an intrinsic QRS >120 msec or a paced QRS duration >200 msec, sinus rhythm or permanent atrial fibrillation/flutter with controlled ventricular beats and a planned ICD implantation
All patients also receiving optimal pharmacotherapy with a β-blocker, ACE inhibitor or ARB, spironolactone, ASA and statins if appropriate

Exclusion Criteria

Recent cardiovascular event or a major coexisting illness
approx 36 months into study, above protocol revised – NYHA class III patients excluded (due to guideline changes and CRT mortality benefit in these patients without ICD)

Follow-Up

Mean of 40 months

Treatment Regimen

CRT to usual care of ICD and optimized medications (CRT+ICD) vs. usual care (ICD)
Clinical assessment and device interrogation at each visit – 1 month after insertion of device and every 6 months at least 18 months until the end of the trial

Results

Primary Endpoints

CRT+ICD ICD Hazard Ratio p
All cause mortality or HF requiring hospitalization for:

All patients
33.2% 40.3% 0.75 (0.64-0.87) <0.001

NYHA class II patients
27.3% 34.7% 0.73 (0.61-0.88) 0.001

NYHA class III patients
55.9% 63.8% 0.76 (0.58-0.99) 0.04

Secondary Endpoints

CRT+ICD
n=894 ICD
n=904 Hazard Ratio p

All cause mortality
20.8% 26.1% 0.75 (0.62-0.91) 0.003

CV mortality
14.5% 17.9% 0.76 (0.60-0.96) 0.02

HF hospitalization
19.5% 26.1% 0.68 (0.56-0.83) <0.001

CRT+ICD
n=708 ICD
n=730 Hazard Ratio p

NYHA Class II
All cause mortality
15.5% 21.1% 0.71 (0.56-0.91) 0.006

CV mortality
10.5% 13.7% 0.73 (0.54-0.99) 0.04

HF hospitalization
16.2% 21.8% 0.70 (0.55-0.89) 0.003

All cause mortality & CV mortality not statistically significant for NYHA class III patients, but HF hospitalization 31.7% (CRT+ICD) vs. 44.3% (ICD); HR 0.63 (0.45-0.88), p=0.006
Adverse effects/events within 30 days of device implantation higher in CRT+ICD (13%) vs. ICD (7%) group (p<0.001), including hemo- or pneumothorax, device pocket hematoma or infections requiring intervention, lead dislodgements requiring intervention, revisions and coronary sinus dissections.

Summary

Addition of CRT to primary ICD therapy reduces death and HF hospitalization in patients with mild symptoms of HF, reduced LVEF and wide ORS duration.