Title: The EP Show: New approaches to heart failure
1The 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
2Pharmacologic 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
3Dosing
- 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
4Diastolic 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
5Resynchronization 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
6Pilot 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
7Functional 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
8Class 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
9COMPANION 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
10COMPANION 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
11CARE-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
12Resynchronization 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
13Differing 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
14Nonresponders
- "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
15Defining 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
16Lead 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
17Optimal 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
18Increased 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
19Advancing 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
20Patient 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
21Patient 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
22Patient 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? -
23Nonischemic 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
24Synchronization 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
25Pacemakers 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
26Long-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
27Pacing 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
28Pacing 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
29Who 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
30Busy 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
31Coordinating 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
32Limited 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
33New 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
34Comorbid 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
35Summary
- 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
36The 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