Download Cardiac Resynchronization Therapy 2016 Update

Cardiac Resynchronization
Therapy 2016 Update
Carl W. Musser, M.D.
Cardiac Electrophysiologist
Carilion Clinic Cardiology
Disclosures
• None
Objectives
1. Review the epidemiology of heart failure and the role of
device-based therapy
2. Discuss the current indications for the use of cardiac
resynchronization therapy (CRT) devices for treatment
of heart failure and prevention of sudden cardiac death
3. Review recent clinical evidence expanding CRT
indications
4. Apply risk stratification strategies and discuss
controversies regarding selection and implantation in
CRT devices in appropriate patients
Heart Failure (HF) Overview
• HF is the inability of the heart to meet the
body’s metabolic demands
• HF is a complex syndrome
– Defined by signs and symptoms
– No straightforward diagnostic test for HF
– Different types of HF
• Acute vs. chronic
• Systolic vs. diastolic
• Left-sided vs. right-sided
Heart Failure Symptoms
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Dyspnea
Orthopnea/PND
Pulmonary edema
Fatigue
Weakness
Exercise intolerance
Edema
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Weight gain
Nausea
Diminished appetite
Nocturia
Fluid retention
Angina
Arrhythmias
NYHA Functional Class
Class
Official Definition
In Everyday Terms
I
No limitation of functional activity or
only at levels of exertion that would
limit normal individuals
Can run up stairs
II
Slight limitation of activity.
Dyspnea and fatigue with moderate
exercise.
Can run up stairs but
is out of breath when
he gets there
III
Marked limitation of activity.
Dyspnea with minimal activity.
Can walk up stairs if
he can rest a couple
of times on the way
IV
Severe limitation of activity.
Symptoms even at rest.
Cannot climb stairs at
all
Chronic Heart Failure
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Affects nearly 6 million Americans
550k new diagnoses each year
1 in 9 deaths - HF is contributing cause
Average hospital stay is ~ 6 days
Estimated cost of HF for 2010 was $30.7B
½ people who develop HF die within 5 yrs
Chronic Heart Failure
Mortality
American Heart Association. Heart Disease and Stroke Statistics. 2005
Readmission and Mortality
• Poor outcomes are common for patients
after hospitalization for heart failure (HF):
1-Year
Readmission Rates
1-Year
Mortality
50%
35%
Kosiborod et al. Am J Med. 2006;119:616.e611–
616.e617.
Rathore et al. Am Heart J. 2006;152:371–378.
Chronic Heart Failure
Optimal Medical Therapy
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Low-salt diet
Beta-blockers
ACE-inhibitor/Angiotensin receptor blockers
ARB/Neprilysin Inbitors
Aldosterone antagonists
Hydralazine and oral nitrates
Diuretics
Cardiac Dyssynchrony
Cardiac Dyssynchrony
Cardiac Dyssynchrony
Synchronous
Dyssynchronous
Cardiac Dyssynchrony
Chronic Heart Failure (Systolic)
Device-Based Therapy
• Patients with impaired LV systolic function
(LVEF <= 35%) while on optimal medical
therapy may benefit from:
Implantable cardioverter defibrillator (ICD)
and (when significant dyssynchrony present)
Cardiac resynchronization therapy (CRT)
Readmission and Mortality
• Poor outcomes are common for patients
after hospitalization for heart failure (HF):
Cardiac
1-Year
1-Year
Resynchronization
Readmission Rates
Mortality
Therapy (CRT) is
associated with
50%
50% reduction in
Kosiborod et al. Am J Med. 2006;119:616.e611–
hospitalization
616.e617.
35%
36% reduction in
mortality
Rathore et al. Am Heart J. 2006;152:371–378.
Coronary Sinus Lead
Placement
Coronary Sinus Lead
Placement
CRT Evidence
• 4,000 patients evaluated in RCT over last 20 years
• Consistent improvement in QOL, functional status, and
exercise capacity
• Strong evidence of changes in LV structure
–  LV volumes and dimensions
–  LVEF
–  Mitral regurgitation
• Reduction in HF and all-cause morbidity and mortality
Early Pivotal CRT Trials
Trial
# Pts
MUSTIC1
MIRACLE2
Contak CD3
COMPANION4
CARE-HF5
Inclusion
Outcome
131
NYHA III
EF<35%
QRS>150
Improved 6m walk, pV02
QoL; reduced hospitalizations
453
NYHA III-IV
EF<35%
QRS>130
Improved 6m walk, pV02
QoL; reduced hospitalizations
490
NYHA II-IV
EF<35%
QRS>120
Composite end-point of allcause mortality, HF
hospitalization or VT/VF
therapy not met
1120
NYHA III-IV
EF<35%
QRS>120
Reduced all-cause mortality
and hospitalization
813
NYHA III-IV
EF<35%
QRS>120
Reduced all-cause mortality
and hospitalization
Linde C et al. JACC 2002;40:111-8. 2 Abraham WT et al. NEJM 2002;346:1845-1853. 3 http://www.fda.gov/cdrh/pdf/P010012b.pdf
4 Bristow MR et al. NEJM 2004;350:2140-50. 5 Cleland JG et al. NEJM 2005;352:1539-49.
1
CARE-HF
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NYHA Functional Class III or IV CHF
Ischemic or Non-Ischemic CM with LVEF <= 35%
LV end-diastolic dimension index of 30 mm or more
QRS duration >= 150 ms or 120-149 ms with:
– 2 of 3 criteria of mechanical dyssynchrony
• Optimal medical therapy
• 813 patients at 82 centers followed for 29 months
• 1:1 randomization to OMT:CRT-P
Cleland JG et al. N Engl J Med 2005;352:1539-49.
CARE-HF
Baseline Characteristics
Cleland JG et al. N Engl J Med 2005;352:1539-49.
CARE-HF
All-Cause Mortality
Cleland JG et al. N Engl J Med 2005;352:1539-49.
CRT for Mild Heart Failure
CRT Trials 2nd Generation
Trial
REVERSE1
MADIT-CRT2
RAFT3
# Pts
Inclusion
Outcome
610
NYHA I-II
EF<=40%
QRS>120ms
Reduced non-fatal heart
failure events. Improved LV
structure and function.
1820
NYHA I-II
EF<=30%
QRS>130ms
Reduced non-fatal heart
failure events. Mortality not
met.
1798
NYHA II-III
EF<=30%
QRS>120ms
Reduced heart failure events
and mortality.
1 Linde C et al. JACC 2008; 52: 1834-1843. 2 Moss AJ et al. NEJM 2009; 361: 1329-38. 3 Tang ASL et al. NEJM 2010; 363: 2385-95
MADIT-CRT
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NYHA Functional Class I or II CHF
Ischemic or Non-Ischemic CM with LVEF <= 30%
QRS duration >= 130 ms
Optimal medical therapy
• 1820 patients at 88 centers followed for 31 months
• 3:2 randomization to CRT-D:ICD
Moss AJ et al. NEJM 2009; 361: 1329-38.
MADIT-CRT
Baseline Characteristics
MADIT-CRT
Heart Failure Events
Moss AJ et al. NEJM 2009; 361: 1329-38.
MADIT-CRT
Death or HF Risk
Moss AJ et al. NEJM 2009; 361: 1329-38.
RAFT Trial
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NYHA Functional Class II or III CHF
Ischemic or Non-Ischemic CM with LVEF <= 30%
QRS duration >= 120 ms or >= 200 ms (paced)
Optimal medical therapy
• 1798 patients at 34 centers followed for 40 months
• 1:1 randomization to ICD:CRT-D
Tang ASL et al. NEJM 2010; 363: 2385-95
RAFT
Baseline Characteristics
Tang ASL et al. NEJM 2010; 363: 2385-95
RAFT
Death or HF Hospitalization Risk
RAFT
Death or HF Hospitalization Risk
Tang ASL et al. NEJM 2010; 363: 2385-95
RAFT
Primary Outcome by NYHA Class
Tang ASL et al. NEJM 2010; 363: 2385-95
RAFT
Death by NYHA Class
Tang ASL et al. NEJM 2010; 363: 2385-95
2010 Expanded CRT Indication
Cardiac Resynchronization Therapy with or
without defibrillator in patients with:
• Ischemic or non-ischemic CM
• LVEF <= 30%
• NYHA functional class I (ischemic) or II
• LBBB with QRS >= 130 ms
Block HF Trial
• NYHA Functional Class I - III CHF
• LVEF <= 50%
• Formal indication for pacing due to AV block
• 918 patients at 60 centers followed for 37 months
• 1:1 randomization to BiV pacing (CRT) :RV pacing
Cutis A et al. NEJM 2013; 368: 1585-93
Block HF
Baseline Characteristics
Block HF
All Cause Mortality
Urgent Care HF Visit
CRT Non-Response
• Convert CRT non-responders
• Deliver 2 impulses from LV lead
Multi-Point Pacing (MPP)
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Reduced activation times and QRS duration1
>20% reduction in mechanical dyssynchrony2
84% improvement in acute LV contractility3
90% Packer Clinical Composite responder rate4
1.
2.
3.
4.
Menardi, E et al, Heart Rhythm 2015; 12(8):1762-69
Rinaldi, CA et al, Journal Cardiac Failure 2013;19:731-38
Thibault, B et al, Europace 2013;15:984-91
Zanon, F et al, Heart Rhythm 2016;13:1644–1651
CRT Controversies
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Echocardiographic dyssynchrony
Atrial fibrillation
Right bundle branch block
Normal QRS
Non-ischemic versus ischemic CM
Elderly
CRT Controversies
Echocardiographic Dyssynchrony
• Patients who meet accepted criteria for CRT
should not have therapy withheld because of
results of an echocardiographic dyssynchrony
study.
Gorcsan J, et al. J Am Soc Echocardiogr 2008; 21(3):191-213
CRT Controversies
Atrial Fibrillation
• 25% of CRT candidates have AF
• Few CRT trials include patients with AF
• Pacing event counters overestimate CRT
– <50% of patients have effective CRT (defined as at
least 90% BV pacing with complete capture).1
• Achieving 90-100% BV pacing likely identifies
patients with higher daily HR which is associated
with worse outcomes.2
1 Kamath GS et al. JACC 2009; 53:1050-55
2 Fox K et al. JACC 2007; 50:823-30
CRT and Right Bundle Branch Block
• RBBB constitutes 10% of ventricular conduction
distubances in HF
• MADIT-CRT (228 pts)1 and RAFT (161 pts)2
– No benefit for death or HR in mild-mod HF
• Medicare Registry (1638 pts)3
– Less LV remodeling.
– No reduction in death or HR
– 40% higher relative risk of 1 and 3 year mortality
1 Zareba W et al., Circ 2011; 123:1061-72.
2 Tang AS et al. NEJM 2010; 363:2385-95.
3 Bilchick KC et al. Circ 2010; 122: 2022-30.
CRT Controversies
Right Bundle Branch Block
• Uncertain benefit of CRT in patients with
right bundle branch block (RBBB)
– ACC/AHA HF Guidelines: “…only a small
number of patients with ‘pure’ (RBBB) have
been enrolled in CRT trials. The effect of CRT
in these patients is currently unknown.”
ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy. JACC 2008; 51:2085-2105
Normal QRS and CRT
• COMPANION study
– 1 year duration
– Randomized CRT-P,
CRT-D, OMT in 2:2:1
ratio
• Subgroup analysis
– Trend toward greater
benefit with
lengthening QRS
Bristow M, et al. N Engl J Med 2004; 350:2140-50.
CRT Controversies
Normal QRS
• QRS is still the best criterion for selection of
CRT patients
• There is not sufficient evidence to withhold CRT
from any patient with a formal indication and a
QRS ≥ 120 ms.
Non-ischemic v. Ischemic CM
• CRT patients with
ischemic etiology have
poorer prognosis and less
improvement in cardiac
function and status than
non-ischemic patients
• Ischemic patients have
comparable survival
benefit
Wikstrom E, et al. Eur Heart J. 2009; 30:782-788 (CARE-HF)
CRT in the Elderly
• Mean age 64 to 67 years in randomized
controlled CRT trials1
• Heart failure is a mostly a disease of the
elderly, which are underrepresented in
controlled CRT study
1. Cleland JG, et al. Eur J Heart Fail 2005;7:205 – 214.
IMPROVE-HF
Underutilization in the Elderly
Yancy C et al. J Cardiac Fail 2007;13(suppl):S158. Abstract 290.
CARE-HF
Elderly Patient Subgroup Analysis
• CRT reduced mortality and morbidity versus
medical treatment alone in patients >= 70 yo
Mabo P et al. Circulation 2008;118:S949 (Abstract 8450)
CRT Controversies
Elderly Patients
• Recent analyses of randomized controlled trials provide
data on the efficacy and safety of CRT in the elderly
– Extended survival, improved quality of life, and improved cardiac
function and status
• Guidelines are the same for elderly patients1
– Life expectancy >1 year
• CRT-P may be considered to extend survival and
improve quality of life in select elderly patients where
defibrillation is not desired
1. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities. J Am Coll
Cardiol, 2008; 51:2085-2105.
Thank you