The EP Show COMPANION and CARE-HF
Eric Prystowsky MD
Director, Clinical Electrophysiology Laboratory
St Vincent Hospital
Indianapolis, IN
Hugh Calkins MD
Director, Electrophysiology Lab
Johns Hopkins University Medical Center
Baltimore, MD
John Cleland MD
Professor of Cardiology
Hull University
Kingston upon Hull, UK
Use of cardiac resynchronization therapy (CRT) in COMPANION and CARE-HF
Brief history
Large group of patients in need of ICDs for primary prevention
New era of biventricular pacing to improve HF symptoms
COMPANION and CARE-HF
Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure
COMPANION
COMPANION
Design
Parallel, randomized clinical trial in 1600 patients with moderate or severe heart failure with QRS >120 ms and PR interval >150 ms (Bristow MR et al. N Engl J Med 2004; 350: 2140-2150)
Patients randomized in a 1:2:2 fashion to optimal medical therapy; optimal drug therapy plus CRT; or optimal drug therapy plus CRT with an ICD (CRT-D)
Results
Primary end point
Combination of all-cause death and all-cause hospitalizations reduced 19% in the CRT study arm and 20% in the CRT-D study arm
Death from or hospitalization for HF reduced 34% in CRT group and 40% in CRT-D group
Results
Secondary end point
CRT alone associated with a nonsignificant trend toward a 24% reduction in all-cause mortality, a secondary end point of the study
CRT with a defibrillator reduced all-cause mortality 36%, a highly significant result
Significant reductions
"This study showed in a large population of patients that resynchronization therapy improves survival and reduces hospitalization."
Survival benefit limited to those with CRT and ICD
Calkins
CRT challenges
Implanting the coronary sinus lead
Difficulty involves not getting the lead in, but getting it in the right place
To achieve effective resynchronization, the lead needs to be implanted in a lateral branch of the coronary sinus
Requires experienced implanter
Cardiac Resynchronization Heart Failure
CARE-HF
CARE-HF
Rationale
Cardiac dyssynchrony a problem in a large number of patients with HF and left ventricular systolic dysfunction
Previous studies have suggested that CRT can improve symptoms, quality of life, and exercise capacity
No conclusive evidence of an effect on hospitalizations or mortality
CARE-HF
Design
Randomized, controlled, open-label, blinded-end-point study
Randomized patients to continue with medical therapy or to receive CRT
Included 813 patients with NYHA class 3-4 HF despite standard drug therapy, an LVEF <35%, and QRS duration of at least 120 ms
CARE-HF
Patients with a QRS duration <150 ms were required to have echocardiographic confirmation of ventricular dyssynchrony
Primary end point was all-cause mortality/unplanned hospitalization for CV event
Strengths of CARE-HF
Study details
Large control group
Implant success rate 96%
Long-term follow-up, with an average of 2.5 years
Average age of patient 67 years
Only 40% of patients taking >80 mg furosemide (most common dose was 40 mg daily)
Cleland JGF et al. N Engl J Med 2005; 352:1539-1549
Primary and secondary outcomes in CARE-HF
Other improvements
CRT group also benefited significantly with improved LVEF, NYHA class, end-systolic volume, mitral-valve function, blood pressure, and quality-of-life indices
Dramatic improvements at 18 months in levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP)
Problems encountered
Lead problems
27 lead-related problems, such as fracture or displacement, in the 409 patients randomized to CRT
Number of cases of coronary sinus dissection, none of which caused death
One procedure-related death in each group
Possible remission
"I think we see a substantial proportion of patients who become asymptomatic and whose cardiac function is normalized by this therapy."
Possibility of HF "remission"
Cleland
What therapy?
No question to the value of CRT, but candidates for CRT are also candidates for ICD therapy
The question then becomes, which treatment do they receive?
Treating patients
"It's a fairly easy decision."
Real difference comes down to cost, but the added protection of the ICD warrants the use of CRT with a defibrillator
Calkins
Other issues
Morbidity
There is the possibility of inappropriate shocks from the ICD in healthy patients who might not stand to benefit from its addition
In studies using older devices, the morbidity from the defibrillator was unacceptable
If money were not an issue . . .
CRT with newer defibrillators does provide an additional benefit
But cost in the UK remains an issue, and I would continue to be selective about which patients received CRT with defibrillator backup
Cleland
Patient selection
Have you learned anything from the studies that would help you select patients for a CRT-D implant?
- Prystowsky
The brief answer to that is not yet.
- Cleland
Inappropriate shocks
Not a case of inappropriate shocks but inappropriate programmers
EPs programming devices that deliver inappropriate shocks more than 5% of the time need to go back to school
Prystowsky
Inappropriate shocks
"It irks me at times because people throw that up as a reason not to get a defibrillator, but I say get a better implanter, get a smarter doctor."
- Prystowsky
"But not everybody can come to your center and benefit from your expertise."
- Cleland
Looking to the future
Interesting issue as not everybody with a wide QRS benefits, and even some with a narrow QRS benefit from CRT
Pathophysiology suggests applying therapy earlier, to patients in NYHA class 2, to prevent progression of HF
Looking to the future
"The fact that CARE-HF was so positive in a rather milder population than COMPANION supports the drift to using these devices at an earlier stage."
Cleland
Patient selection
Some patients have such dramatic improvements with CRT that they may no longer be candidates for an ICD
Need more research on the benefit of the defibrillator in CRT-D therapy
Conclusions
Summary
Patient who meets criteria for resynchronization should be treated accordingly
Defibrillator component remains to be debated, mainly due to the issue of economics
Conclusions
CARE-HF showed major reductions in mortality with pacing alone
"The world is better off for the fact that we've had these two studies."
- Prystowsky