Mr. J is a 70 year old man with an ischemic cardiomyopathy who presents with class III CHF and significant dissatisfaction with his functional capacity (can only walk 100-200 yards on the level). Past history is significant for an anterior MI, intermittent atrial fibrillation, and a dual chamber ICD implant in 2002 for syncope, a positive TWA stress test, and inducible VT at EPS. His medicines include digoxin 0.125 mg QD, amiodarone 200 mg QD, Lasix 40 mg QD, Coreg 12.5 mg BID, and lisinopril 5 mg QD. Aldactone was stopped due to hyperkalemia and azotemia. A BP of 88/56 has prevented more aggressive drug Rx.

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Work-up revealed a QRS duration Work-up revealed a QRS duration of 120-130 ms (paced). His EF was of 120-130 ms (paced). His EF was 25% on echo, with a severely 25% on echo, with a severely dilated LV, 4+ MR, and a PA dilated LV, 4+ MR, and a PA pressure of 54 mm. Additional pressure of 54 mm. Additional echo Doppler assessment for CRT echo Doppler assessment for CRT demonstrated a prolonged aortic demonstrated a prolonged aortic pre-ejection interval (350ms, >160 pre-ejection interval (350ms, >160 ms suggests response to CRT) and ms suggests response to CRT) and tissue Doppler findings of a tissue Doppler findings of a prolonged interval (100 ms) prolonged interval (100 ms) between earliest and latest peak between earliest and latest peak systolic velocity (comparing 6 basal systolic velocity (comparing 6 basal wall segments).wall segments).

The patient underwent upgrade The patient underwent upgrade of his ICD to a CRT-D device in of his ICD to a CRT-D device in 3/04, as part of a clinical trial 3/04, as part of a clinical trial investigating the utility of investigating the utility of sequential biventricular pacing sequential biventricular pacing in CRT (InSync III Trial, in CRT (InSync III Trial, Medtronic).Medtronic).

Six months post implant, the patient is NHHA Six months post implant, the patient is NHHA Class I (asymptomatic). He exercises 3 days Class I (asymptomatic). He exercises 3 days weekly for approximately 2 hours at a time. His weekly for approximately 2 hours at a time. His Six Minute Hall Walk Test in 9/04 measured Six Minute Hall Walk Test in 9/04 measured 2000 feet, almost a 300% increase from his 2000 feet, almost a 300% increase from his baseline of 675 feet pre-CRT. His BP was baseline of 675 feet pre-CRT. His BP was 114/67 prior to his walk and 132/70 after 114/67 prior to his walk and 132/70 after ambulation, with an increase in HR from 60 to ambulation, with an increase in HR from 60 to 66 with ambulation and an O2 sat of 99% 66 with ambulation and an O2 sat of 99% during ambulation.during ambulation.

Cardiac Cardiac Resynchronization Resynchronization

Therapy (CRT)Therapy (CRT)In patients with significant symptoms of In patients with significant symptoms of CHF, intraventricular conduction delay on CHF, intraventricular conduction delay on ECG (QRS>120 ms), and EF <35%, CRTECG (QRS>120 ms), and EF <35%, CRT

• is safe and well toleratedis safe and well tolerated

• improves quality of life, functional class, improves quality of life, functional class, exercise capacity exercise capacity

• improves cardiac structure and functionimproves cardiac structure and function

Bradley JAMA 2003

COMPANION Trial (COMPANION Trial (Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure) : ) : HypothesisHypothesis

“Prophylactic cardiac resynchonization therapy in the form of biventricular stimulation with a pacemaker, with or without a defibrillator, will reduce the risk of death and hospitalization in patients with advanced chronic heart failure and intraventricular conduction delays.”

Key Inclusion CriteriaKey Inclusion Criteria

• NYHA Class III or IV• NSR, >=QRS 120 ms, PR interval >150ms• LVEF <=35%, LVEDD >=60 mm• Optimal pharmacological therapy

• Beta blocker (for at least 3 months)• Diuretic, ACEI/ARB, spironolactone (1 month); +/- digoxin

• Hx of CHF hospitalization (or equivalent) <12 months, >1 month prior to enrollment

• No bradycardiac or tachyarrhythmic device indication at the time of enrollment

Study DesignStudy Design

• OPT1

• OPT

• CRT+

2

• OPT

• CRT-D+

2

Randomization

Parallel Randomized design

Results (n=1520 patients)Results (n=1520 patients)Secondary endpoint – Death from any cause

The DataThe Data

• Based on these results:Based on these results:• 14 CRT-D devices would have to be placed 14 CRT-D devices would have to be placed

to save one life at 12 mos.to save one life at 12 mos.• The majority of events, and the driving The majority of events, and the driving

force behind the endpoints was force behind the endpoints was hospitalizations.hospitalizations.

• This study was not adequately powered to This study was not adequately powered to determine a difference between CRT and determine a difference between CRT and CRT-D.CRT-D.

Relative Cost of CRTRelative Cost of CRT

Cost per patient

$0$20$40$60

CRT+ICD

CRT

Hip/ knee replace

PTCA

CABG

Dialysis

$ thousands

Total Annual Expenditures

$0 $5 $10 $15 $20

$ Billions

Not all patients Not all patients benefit from CRTbenefit from CRT

•Electrical dyssynchrony on Electrical dyssynchrony on ECG does not necessarily ECG does not necessarily indicate mechanical indicate mechanical dyssynchrony.dyssynchrony.

•Tissue doppler may have a Tissue doppler may have a role in optimizing the role in optimizing the selection of patients for CRT.selection of patients for CRT.