Implantable Devices for Heart Failure: Whats New

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Implantable Devices for Heart Failure Whats New?

• Derek T. Connelly
• President Heart Rhythm UK
• Consultant Cardiologist, Glasgow Royal Infirmary
• February 2006

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Prevalence of CHF by Age, U.S.
Source National Heart, Lung, and Blood Institute
2001
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Benefit of medical therapymild to moderate HF
and LV systolic dysfunction

• digoxin and diuretics 2 year mortality 34
  (1986)

()
ß Blocker
ACE-i ARB
Spironolactone
- 0
- 10
- 20
1986
1999 Total mortality 34
14
- 30
Cleland J et al. Prog Cardiovasc Ds 200143433
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Long-Term Trends in the Incidence of and Survival
with Heart Failure (Framingham Cohort 1075
subjects 51 females )
Levy D et Al. N Engl J Med 2002 347 1397-1402
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Classification of severity of symptoms

• New York Heart Association
• Class I Asymptomatic
• Class II Symptoms on moderate exertion
• Class III Symptoms on mild exertion
• Class IV Symptoms at rest

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Sudden Cardiac Death a predominant mode of death
in heart failure patients
Class IV
Class III
Class I
NYHA Class III
Class II
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Increased Mortality Rate with LBBB
All patients N 5517
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LBBB N1391
HR 1.70 (1.41-2.05)

• Increased 1-year mortality with presence of
  complete LBBB (QRS gt 140 ms)
• Risk remains significant
• even after adjusting for
• age
• underlying cardiac disease
• indicators of HF severity
• HF medications

16.1
15
11.9
1-Year Mortality ()
HR 1.58 (1.21-2.06)
10
7.3
5
5.5
0
All Cause
Sudden Cardiac
HR Hazard Ratio
Cause of Death
Baldasseroni S, Opasich C, Gorini M, et al. Am
Heart J 2002143398-405
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Technique for Biventricular Pacing

• Standard implant procedure extra guidewire /
  sheath in subclavian vein
• Long guiding sheath to coronary sinus
• Coronary sinus angiogram (LAO and RAO views) with
  occlusion balloon
• Advance guidewire to the chosen coronary vein and
  thread lead over wire
• Test pacing, sensing, impedance check for
  diaphragmatic twitching
• Implant other leads (RA, RV)

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Technical Challenges

• Combination of skills
• Pacemaker implant
• Coronary sinus catheterisation (EP / RFA skill)
• Selection of branches (angiographic skill)
• Over-the-wire leads (PCI skill)
• Guidewires / leads going against direction of
  blood flow
• Technically more difficult
• Dissection is less problematic
• Different hardware from different companies
• Phrenic nerve stimulation

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Technical challenges

• Tendency to take on patients with severe LV
  dysfunction
• Enlarged RA, RV, LA, LV
• Coronary veins overlying damaged myocardium
• ICD implants in patients with Class 4 heart
  failure difficulty in defibrillation
• Wide variation in procedure times
• 50 mins 4 hours
• Mean 1.5 -2 hours for experienced operator

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Assessment of Efficacy

• Acute haemodynamic changes (arterial pressure, LV
  dP/dt)
• Echo
• Doppler pattern of mitral inflow
• Tissue Doppler
• Optimise AV delay ( VV delay)
• Symptoms, exercise capacity, NYHA Class
• Crossover studies, e.g. MUSTIC, PaTh-CHF
• Randomised controlled trials, e.g. MIRACLE,
  COMPANION, CARE-HF

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Exercise Capacity during CRT
8
22
28
15
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MUSTIC Results
Cazeau et al New Engl J Med 2001 344 873-80
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Nelson et al. Circulation. 20001023053
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MIRACLE Study

• 453 pts, NYHA 3-4, LVEF lt 35, QRS gt130 ms
• Resynchronisation or control for 6 months
• Resync goup had improved 6 min walk, functional
  class, QOL, exercise time and LVEF
• Fewer pts in the resync group required
  hospitalisation (8 v 15) or IV meds (7 v 15)
• Abraham et al. New Engl J Med 2002 3461845-53

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MIRACLE - 6 min walk quality of life
Abraham et al. New Engl J Med 2002 3461845-53
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MIRACLE - Death or hospitalisation for worsening
heart failure
P 0.03
Abraham et al. New Engl J Med 2002 3461845-53
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Randomised controlled trials of CRT

• Meta-analysis of CONTAK-CD trial, InSync ICD
  trial, MIRACLE and MUSTIC
• CRT reduced death from progressive heart failure
  by 51 (OR 0.49, 95 CI 0.25-0.93)
• CRT reduced heart failure hospitalisation by 29
  (OR 0.71, 95 CI 0.53-0.96)
• Trend to ? all-cause mortality
• Bradley et al 2003 JAMA 289 730-739

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Long Term Benefit Quality of Life
PATH CHF
Auricchio A. Stellbrink C, Sack S, et al.
Long-term benefit as a result of pacing
resynchronization in congestive heart failure
results of the PATH CHF trial. Circulation
2000102(18) (suppl2)693. Abstract 3352
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Functional capacity Six-Minute Walk
PATH CHF
475
450
425
Meters
400
375
350
325
pre-implant
4 weeks
8 weeks
12 weeks
6 months
12 months
n20
n20
n20
n20
n20
n20
Auricchio A. Stellbrink C, Sack S, et al.
Long-term benefit as a result of pacing
resynchronization in congestive heart failure
results of the PATH CHF trial. Circulation
2000102(18) (suppl2)693. Abstract 3352
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CARE-HF Aims

• To assess the effect on morbidity and mortality
  of adding CRT to optimised pharmacological
  therapy in patients with moderate and severe HF
  due to LVSD complicated by cardiac dyssynchrony
• To investigate the mechanisms underlying the
  observed effect to identify markers predicting
  success or failure of CRT
• Cleland JG et al New Engl J Med 2005 352
  1539-40
• (14 April 2005)

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Main Inclusion Exclusion Criteria

• Heart failure for at least 6 weeks requiring loop
  diuretics
• Currently in NYHA class III/IV
• A high standard of pharmacological therapy
• LV systolic dysfunction and dilation
• EF ?35 EDD ?30mm/height in metres
• QRS ?120 ms
• Dyssynchrony confirmed by echo if QRS 120-149 ms
• Aortic pre-ejection delay gt140ms
• Interventricular mechanical delay gt40 ms
• Delayed activation of postero-lateral LV wall
• Patients with AF or requiring pacing were
  excluded
• Cleland JG et al New Engl J Med 2005 352
  1539-40
• (14 April 2005)

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Conduct of the Study

• Recruitment
• 813 patients (Jan 2001 - Mar 2003)
• 82 centers in 12 countries
• Austria, Belgium, Denmark, Finland, France,
  Germany, Italy, Netherlands, Spain, Sweden,
  Switzerland, and UK
• Implant success rate 96
• Median time to implant 4 days (IQR 2-7)
• At completion (30th September 2004)
• lt5 cross-over before primary endpoint
• Survival status ascertained on all patients
• Mean follow-up from randomization 29.4 months
• Cleland JG et al New Engl J Med 2005 352
  1539-40
• (14 April 2005)

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Baseline Characteristics (1)
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Baseline Characteristics (2)
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Primary Endpoint(All-cause Mortality or
Unplanned Hosp. for Major CVS Event)
1.00
0.75
0.50
Event-free Survival
Medical Therapy
0.25
0.00
0
500
1000
1500
Days
Number at risk
7
68
166
273
323
409
CRT
3
48
118
232
292
404
Medical Therapy
30
Primary Endpoint(All-cause Mortality or
Unplanned Hosp. for Major CVS Event)
Number at risk
7
68
166
273
323
409
CRT
3
48
118
232
292
404
Medical Therapy
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Primary Endpoint(All-cause Mortality or
Unplanned Hosp. for Major CVS Event)
No statistical significant heterogeneity in
subgroups
Number at risk
7
68
166
273
323
409
CRT
3
48
118
232
292
404
Medical Therapy
32
All-Cause Mortality
1.00
0.75
0.50
Event-free Survival
Medical Therapy
0.25
0.00
0
500
1000
1500
Days
Number at risk
8
89
213
351
376
409
CRT
5
71
192
321
365
404
Medical Therapy
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All-Cause Mortality
1.00
HR 0.64 (95 CI 0.48 to 0.85)
0.75
CRT
P .0019
0.50
Event-free Survival
Medical Therapy
0.25
0.00
0
500
1000
1500
Days
Number at risk
8
89
213
351
376
409
CRT
5
71
192
321
365
404
Medical Therapy
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Symptoms Quality of Life at 90 days
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Mechanistic Outcomes

• At 18 months, compared to the control group,
  patients randomized to CRT had
• Shorter Interventricular Mechanical delay P lt
  0.0001
• Higher LVEF (by about 7) P lt 0.0001
• Less mitral regurgitation P 0.003
• Lower ventricular volumes P lt 0.0001
• Higher systolic blood pressure P lt 0.0001
• Lower NT-pro-BNP P lt 0.0016

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Procedure or Device RelatedSerious Adverse Events
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Conclusions

• CRT should be considered as part of routine
  therapy for patients with moderate to severe HF
  due to LVSD with evidence (ECG supported by Echo)
  of cardiac dyssynchrony to
• Improve cardiac function and efficiency
• Improve symptoms and QoL
• Reduce morbidity
• Prolong survival
• These benefits are in addition to those of
  pharmacological therapy
• Cleland JG et al New Engl J Med 2005 352
  1539-40
• (14 April 2005)

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Pacing for Heart FailureWhich patients need
ventricular resynchronisation?

• Very poor LV systolic function (LVEF lt 35)
• NYHA Class II IV
• Persistent symptoms despite optimum drug Rx
• Wide QRS - LBBB pattern
• gt 120 ms? ( echo evidence of dyssyncrony)
• gt 150 ms?
• Additional factors which may improve benefit
• Normal or prolonged PR interval
• Presystolic MR or TR

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Pacing for Heart FailureUnanswered questions

• Role of BiV pacing in patients requiring pacing
  for AV block poor LV function
• Which patients need an ICD?
• Is NYHA Class IV heart failure still a
  contraindication to ICD?
• What to do about ICD candidates with poor LV,
  wide QRS but mild symptoms?
• Implant failure in 5 - 10 - what to do?
• ? Surgical LV lead implant
• ? Endocardial (transseptal) approach
• What is the best way to optimise therapy?
• Pacing parameters
• Drug therapy post-implant

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Pacing for Heart FailureWho needs ICD backup?

• MADIT - 2 Study
• Patients post - MI with LVEF lt 30
• Significant improvement in survival in patients
  randomised to receive ICD
• 31 reduction in total mortality with ICD
• greater benefit in patients with wide QRS

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MADIT II Results
Moss et al New Engl J Med 2002 346 877-883
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MADIT II - Subgroup analysis
Moss et al New Engl J Med 2002 346 877-883
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Devices for Heart FailureBiventricular Pacing or
ICD - or both?

• BiV Pacing Studies
• NYHA 2-4
• LVEF lt 35
• No upper age limit
• CAD or DCM
• Improved QOL
• Wide QRS (gt130 - 150 ms)

• MADIT - 2 (ICD)
• NYHA 1-3
• LVEF lt 30
• No upper age limit
• CAD
• Improved survival
• Greatest survival benefit when QRS gt 120 ms

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Conclusions

• Many patients with heart failure, poor LV
  systolic function and wide QRS will benefit from
  biventricular pacing
• Most will also be candidates for ICD
• No trials have been powered to detect a
  significant difference between CRT alone and CRT-D

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Revised NICE ICD GuidanceJanuary 2006

• NATIONAL INSTITUTE FOR HEALTH AND CLINICAL
  EXCELLENCE
• Final Appraisal Determination
• Implantable cardioverter defibrillators for
  arrhythmias
• (review of existing guidance no. 11)
• Guidance
• This appraisal does not cover the use of
  implantable defibrillators for non-ischaemic
  dilated cardiomyopathy.
• Implantable cardioverter defibrillators (ICDs)
  are recommended for patients in the following
  categories.
• Secondary prevention, that is, for patients who
  present, in the absence of a treatable cause,
  with one of the following
• having survived a cardiac arrest due to either
  ventricular tachycardia (VT) or ventricular
  fibrillation (VF)
• spontaneous sustained VT causing syncope or
  significant haemodynamic compromise
• sustained VT without syncope or cardiac arrest,
  and who have an associated reduction in ejection
  fraction (EF) (LVEF lt 35) (no worse than
  class III of the New York Heart Association
  functional classification of heart failure).

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Revised NICE ICD GuidanceJanuary 2006

• Primary prevention, that is, for patients who
  have
• a history of previous (gt 4 weeks) myocardial
  infarction (MI) and
• either
• left ventricular dysfunction with an LVEF of less
  than 35 (no worse than class III of the New York
  Heart Association functional classification of
  heart failure), and
• non-sustained VT on Holter (24-hour
  electrocardiogram ECG) monitoring, and
• inducible VT on electrophysiological (EP) testing

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Revised NICE ICD GuidanceJanuary 2006

• Primary prevention, that is, for patients who
  have
• a history of previous (gt 4 weeks) myocardial
  infarction (MI) and
• either
• left ventricular dysfunction with an LVEF of less
  than 35 (no worse than class III of the New York
  Heart Association functional classification of
  heart failure), and
• non-sustained VT on Holter (24-hour
  electrocardiogram ECG) monitoring, and
• inducible VT on electrophysiological (EP) testing
• or
• left ventricular dysfunction with an LVEF of less
  than 30 ( no worse than class III of the New
  York Heart Association functional classification
  of heart failure) and
• QRS duration of equal to or more than 120
  milliseconds

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• a familial cardiac condition with a high risk of
  sudden death, including long QT syndrome,
  hypertrophic cardiomyopathy, Brugada syndrome,
  arrhythmogenic right ventricular dysplasia
  (ARVD), or have undergone surgical repair of
  congenital heart disease

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Implications of new NICE guidance

• Patients post-MI with poor LV function (LVEF
  lt30) and QRS width gt 120 ms will routinely be
  considered eligible for ICD
• Routine care post-MI will include aspirin,
  statin, ACE-I, ß blocker, and ICD (in this
  subgroup)

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Implications of new NICE guidance

• Current ICD implant rate 50/ 106 /y
• Approx 1/3 of eligible patients get treated
• Likely to increase to 100 / 106 / y
• Assuming 1/3 of eligible patients treated
• True figure ought to be 300/ 106 /y
• Equal to current pacemaker implant rate

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Treatment of Heart Failure
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Treatment of Heart Failure
Angiotensin/ aldosterone inhibition
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Treatment of Heart Failure
Angiotensin/ aldosterone inhibition
Beta blockade
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Treatment of Heart Failure
Angiotensin/ aldosterone inhibition
Beta blockade
Cardiac resynchronisation
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Treatment of Heart Failure
Angiotensin/ aldosterone inhibition
Beta blockade
Cardiac resynchronisation
Defibrillation