ep show – march 2003 heart failure the ep show: new approaches to heart failure eric prystowsky md...

EP Show – March 2003

Heart Failure

The EP Show: New approaches to heart failure

Eric Prystowsky MDDirector, Clinical Electrophysiology Laboratory St

Vincent Hospital Indianapolis, IN

Leslie Saxon MD Director of ElectrophysiologyUniversity of Southern California Los Angeles, CA

Gary Francis MD Director of Coronary Care UnitCleveland Clinic FoundationCleveland, OH


Heart Failure

Pharmacologic approach

Dramatic changes in the past 15 to 20 years

ACE inhibitors and beta blockers are the cornerstone of therapy

•Loop diuretics, spironolactone, and various adjunctive therapies remain

Francis


Heart Failure

Dosing

Dosing in real practice rarely reflects dosing in controlled clinical trials

•Dosing should be titrated up gradually (over several weeks)

•Using higher doses than those used in trials is controversial; there is no strong data supporting higher doses

Francis


Heart Failure

Diastolic heart failure

We currently have no trials to dictate practice in these patients

•In my practice I tend to treat these patients with diuretics (careful not to create a hypovolemic state)

•These patients respond to ACE inhibitors and beta blockers

•A regimen of ACE inhibitors, beta blockers, and diuretics seems to work

Francis


Heart Failure

Resynchronization therapy

Epidemiological outcome studies showed bundle branch block had a negative impact on mortality

•Early 1990s: Heart failure patients with RV pacemakers didn't do very well

•Mid-1990s: The presence of bundle branch block worsens hemodynamics

•Pacing both ventricles simultaneously seemed to improve the hemodynamics

Saxon


Heart Failure

Pilot studies

3 biventricular pacing trials gained approval for resynchronization devices in the US

• MIRACLE

• InSync ICD

• CONTAK CD

Resynchronization therapy is now indicated for NYHA class 3 patients with QRS delay

Saxon


Heart Failure

Functional improvement

All resynchronization therapy studies showed improvement in functional status:

• Symptom status

• 6-minute walk

• Quality of life

• Peak oxygen consumption

• Modest reverse remodeling

Saxon


Heart Failure

Class 2 patients

Therapy is labeled for class 3 patients, but the ICD trials did enroll class 2 patients

Class 2 patients showed no significant improvement in symptoms but did show remodeling benefit

Saxon


Heart Failure

COMPANION: Enrollment

Enrollment began in 1998, enrolled 1600 patients with

• QRS>120 ms

• P-R interval>150 ms

• Class 3 heart failure

• Hospitalization for heart failure in the past year


Heart Failure

COMPANION: End points

Patients were randomized to optimal medical therapy, cardiac resynchronization, or resynchronization with an ICD

Trial stopped in November 2002:

• 20% reduction in all-cause mortality and all-cause hospitalization in both device groups

• 40% reduction in all-cause mortality in patients who received the combined resynchronization/ICD device


Heart Failure

CARE-HF: Enrollment

Enrollment began in 2001, enrolled 800 patients with

• NYHA class 3/4

• 18-month follow-up

• Randomized to resynchronization or optimal medical management


Heart Failure

Resynchronization therapy

It appears to meet the 3 goals of heart failure therapy

• Improves functional status

• Slows disease progression

• Improves mortality and hospitalization

end points

Saxon


Heart Failure

Differing response

Patients on cardiac resynchronization fall into 3 categories:

• Fabulous response, can improve up to 2 heart classes

• "Tweeners" who get some benefit but not as much as we would like

• 20% to 25% who don't respond at all

Prystowsky


Heart Failure

Nonresponders

"This is the science that is going to keep the next generation of people busy."

We don't understand the relationship between QRS delay and mechanical dysynchrony

Saxon


Heart Failure

Defining resynchronization

We don't understand how to define resynchronization

• QRS delay correlates with ventricular size but does not predict clinical response

• No gold standard of measuring mechanical dysynchrony or resynchronization--we simply don't know what the best measure is

Saxon


Heart Failure

Lead location

Are nonresponders the result of bad lead placement?

• Left bundle-branch block is an incredibly heterogeneous condition, and lead placement will be very patient specific

• You should be able to get response in 70% or so even without perfect lead placement

Saxon


Heart Failure

Optimal programming We could get better results just from optimal programming of AV delay

• New devices offer new options, but there is no established standard way to assess resynchronization

• In my lab we are using echo to follow patients and treating the instrument like a drug, altering the parameters and finding the best response

Saxon


Heart Failure

Increased expectations

Like all therapies, we found something that works, and now we demand better and better results

"I'm getting from your thoughts that we know the therapy works; we have a lot of fine-tuning to do."

Prystowsky


Heart Failure

Advancing the field

Since market approval, >40 000 have been implanted in the US

These devices and patients require a lot of attention; the science needs to be resolved

"I've had several heart failure people come up to me and say, 'You know in the clinical trials our guys were getting results with implants of 70, 80, 90, 90-plus percent and now I think our results aren't as good."

Saxon


Heart Failure

Patient selection

At what point do you send a patient for resynchronization therapy?

• It's not entirely clear, but the threshold for implantation is getting lower and lower

• We find about one third of patients don't get better or have no change

• We might accept those numbers if this were a drug

Francis


Heart Failure

Patient selection

Candidates for resynchronization

• Class 3 patient on full therapy who is still clinically struggling

• Patients with late class 2 and possibly lower if we can refine the selection criteria

• Patients receiving modified Dor procedure who don't do well

Francis


Heart Failure

Patient dilemma

Patient with class 3 heart failure who isn't doing as well as we would like

• IBCD

• QRS duration 140 ms

• EF 25%

Is there any use for a biventricular pacemaker as opposed to a defibrillator in light of what we know about COMPANION?


Heart Failure

Nonischemic cardiomyopathy

"In most instances I would at least bring up the discussion of the defibrillator."

Defibrillators have not yet proved benefit in patients with nonischemic cardiomyopathy

At least 40% of patients in COMPANION had nonischemic cardiomyopathy

As heart failure progresses, the etiology may become less relevant

Saxon


Heart Failure

Synchronization device alone

There is a role for just synchronization therapy in advanced heart failure patients who have very poor outlook for 6-month survival

• Start with a resynchronization device and if they respond well put in an ICD

• It is no good if you put in an ICD, they don't get better, you give them lots of shocks and then have to take the ICD out

Saxon


Heart Failure

Pacemakers as prevention

Could a pacemaker prevent class 2 patients from becoming class 3?

• Does the antiremodeling effect become permanent if you pace long enough?

• If there were permanence you could make an argument to use pacemakers in less-ill patients

Francis


Heart Failure

Long-term pacing

Follow-up on the chronic trials goes out to 1 year

• The remodeling appears to be a direct effect of pacing

• Out to 1 year, volumes improve but mass does not change

• We don't see the same structural changes as with drugs, but it may happen in the future

Saxon


Heart Failure

Pacing damage

Pacing just the right ventricle may alter the heart in a negative way

The recognition that we can create dysynchrony that hurts the ventricle should make us rethink pacing just the right side

Francis


Heart Failure

Pacing the left ventricle

Patients with significant mitral regurgitation can be risky to pace just the right ventricle

• Especially ones with an AV junction ablation can end up in the OR

Now that we have other options, we should think things through before just putting in an RV lead

Prystowsky


Heart Failure

Who follows these patients?

Electrophysiologists are putting the devices in, but should they follow up?

Will heart failure specialists have to learn how to implant these devices?

How would you develop a program for training for the future?

Prystowsky


Heart Failure

Busy EP doctors

Electrophysiologists are just too busy to see these patients

It's unrealistic to expect them to come out of the lab 1 or 2 days a week to see these patients

We should expect a loose affiliation between heart failure specialists and EPs

Francis


Heart Failure

Coordinating care

We scheduled the pacemaker clinic with the heart failure clinic to allow better coordination of care

We trained heart failure fellows in EP for 3 or 4 months to give them an understanding of the device area

EPs could subspecialize into complex ablation and device specialists who do implantation and follow-up

Saxon


Heart Failure

Limited resources

Electrophysiologists don't know enough about the pharmacologic management of these patients

In a small group, you don't have a specialist who can focus on the medical management

This will have to be a part of training in the future because these devices are put in on top of medical therapy

Prystowsky


Heart Failure

New pharmacological approaches

Additional neurohormonal antagonist agents have not proved effective

• TNF-alpha blockers weren't effective

• Omapatrilat wasn't effective

There is a move to comorbid conditions

Francis


Heart Failure

Comorbid conditions

15% to 20% of heart failure patients are anemic

2 companies launching trials with erythropoeitin to address the anemia

Also a move to develop drugs to augment renal function

• Arginine vasopressin antagonists

• Adenosine antagonists

Francis


Heart Failure

Summary

Initial approach should be to optimize pharmacologic treatment of heart failure patients

Patients who remain in class 3 failure with significant QRS duration are candidates for a resynchronization device, probably with an ICD

Once you have a device you need to be managed carefully by specialists

Prystowsky


Heart Failure

The EP Show: New approaches to heart failure

Eric Prystowsky MDDirector, Clinical Electrophysiology Laboratory St

Vincent Hospital Indianapolis, IN

Leslie Saxon MD Director of ElectrophysiologyUniversity of Southern California Los Angeles, CA

Gary Francis MD Director of Coronary Care UnitCleveland Clinic FoundationCleveland, OH

ep show – march 2003 heart failure the ep show: new approaches to heart failure eric prystowsky md...

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