The EP Show: New approaches to heart failure

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The EP Show New approaches to heart failure

• Eric Prystowsky MD Director, Clinical
  Electrophysiology Laboratory
  St Vincent Hospital Indianapolis, IN
• Leslie Saxon MD Director of Electrophysiology U
  niversity of Southern California Los Angeles,
  CA
• Gary Francis MD Director of Coronary Care
  Unit Cleveland Clinic Foundation Cleveland, OH

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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

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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

4
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

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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

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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

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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

8
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
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COMPANION Enrollment

• Enrollment began in 1998, enrolled 1600 patients
  with
• QRSgt120 ms
• P-R intervalgt150 ms
• Class 3 heart failure
• Hospitalization for heart failure in the past
  year

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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

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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

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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

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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

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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

15
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

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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

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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

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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
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Advancing the field
Since market approval, gt40 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
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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

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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

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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?

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Nonischemic cardiomyopathy
"In most instances I would at least bring up
the discussion of the defibrillator." Defibrillat
ors 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
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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

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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

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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

27
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
28
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

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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

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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

31
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
32
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

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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

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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

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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

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The EP Show New approaches to heart failure

• Eric Prystowsky MD Director, Clinical
  Electrophysiology Laboratory
  St Vincent Hospital Indianapolis, IN
• Leslie Saxon MD Director of Electrophysiology U
  niversity of Southern California Los Angeles,
  CA
• Gary Francis MD Director of Coronary Care
  Unit Cleveland Clinic Foundation Cleveland, OH