Heart Failure Update: A Device Perspective James L. Cockrell, Jr., MD Founding Director, Cardiac Electrophysiology Washington Adventist Hospital April 13th, 2013
What is Heart Failure?
Heart Failure: Defined
A syndrome of inadequate tissue perfusion (or the requirement for higher cardiac volumes or filling pressures to maintain perfusion)
Heart Failure: Abnormal Mechanics
Heart Failure:
Cardinal Manifestations Dyspnea and fatigue –often limiting exercise Fluid retention –leading to pulmonary and peripheral edema Impaired quality-of-life
Progressive disorder Symptoms eventually at rest or with minimal exertion Deterioration of cardiac structure and function without recurrent injury, “silently”
The Epidemic of Heart Failure
A Growing Medical Challenge Heart failure management Annual Incidence
Heart Failure Prevalence
Annual Mortality
U.S.
550,000
6.5 million
350,000
Europe
750,000
8.5 million
600,000
Congestive heart failure worldwide markets, clinical status and product development opportunities. New Medicine, Inc. 1997:1-40. Wilkerson Group Survey, 1998.
Incidence of Heart Failure by Age Doubles every decade Framingham Results 35
31
Men
30
Women
25 Average incidence/ 20 1000/year
15
15 10 5
4
8
2
0 45–54
55–64 65–74 Age (years)
Adapted with permission from Kannel WB. Eur J Clin Pharmacol 1996;49(suppl 1):S3
75–84
85–94
Prevalence by severity (NYHA Class) Class III 1.20 M (25%)
Class IV 240 K (5%)
Class I 1.68 M (35%)
Class I
No limitations of physical activity Class II Slight limitations Class III Marked limitations
70 % of patients have little or no symptoms
Class IV Symptoms at rest Class II 1.68 M (35%)
AHA Heart and Stroke Statistical Update 2001
Heart Failure Hospitalizations
CDC/NCHS: Hospital discharges include living patients and in hospital deaths AHA, 1998 Heart and Statistical Update NCHS, National Center for Health Statistics
AHA Heart and Stroke Statistical Update 2001
Causes of Hospital Readmission for Congestive Heart Failure Diet Noncompliance 24%
16% Inappropriate Rx
Vinson J Am Geriatr Soc 1990;38:1290-5
Rx Noncompliance 24%
17% Other
19% Failure to Seek Total HF Costs = $38.1 billion Care
(5.4% of total healthcare costs)
Therapeutic Goals
Treatment Goals for Heart Failure Therapy Goal: Improve the Quality and Quantity of Life Objectives
Relieve symptoms and improve exercise tolerance Prevent sudden death, arrhythmias Slow progression of the underlying disease Decrease ER visits, hospitalizations, and costs Prevent complications, such as atrial fibrillation, stroke
Historical Therapy For Heart Failure
Drug Therapy
Enalapril Reduces Mortality in Heart Failure (SOLVD trial 1991)
16% Reduction in Mortality
Metoprolol Reduces Mortality in Heart Failure (MERIT-HF trial 1999)
34% Reduction at One Year
Spironolactone Reduces Mortality in Heart Failure (RALES trial 1999) 30% Reduction in Mortality
Results of Heart Failure Therapy
More than one drug is needed and they work synergistically
Optimal drug therapy in combination reduces mortality by about a third
So How Could Device Therapy Help?
Mechanism of Death in HF Other 15%
Other 24% SCD 64%
1
CHF 12%
SCD 59%
CHF 26%
SCD 33%
1
Other 11%
CHF 56%
NYHA class II
NYHA class III
NYHA class IV
No. of deaths n = 103
No. of deaths n = 232
No. of deaths n = 27
MERIT-HF Study Group. Lancet 1999;353:2001-2007. (Permission for use requested)
Magnitude of SCA in the US 167,366
Stroke3
Lung Cancer2
157,400
SCA claims more lives each year than these other diseases combined
450,000 SCA 4
#1 the U.S.
Breast Cancer2
40,600 42,156
AIDS1
1
2
U.S. Census Bureau, Statistical Abstract of the United States: 2001. American Cancer Society, Inc., Surveillance Research, Cancer Facts and Figures 2001. 3 2002 Heart and Stroke Statistical Update, American Heart Association. 4 Circulation. 2001;104:2158-2163.
SCD: Ventricular Fibrillation
The Defibrillator
The Implantable Defibrillator Then Initially Defibrillation only
Surgical implant during CABG
Evolution to Subclavicular
ICD Trials Summary Relative Reduction in All-cause Mortality 60%
60% 54% 50% 40% 30%
31%
31% 23%
20%
20% 10% 0% AVID 3 years n=
1016
CIDS 3 years 659
MADITT MUSTT MADITT II SCD-HeFT 2 years 2 years 2 years 5 years 196
704
1232
2521
Results of Heart Failure Therapy Optimal drug therapy in combination reduces mortality by about a third Defibrillator therapy improves survival an additional 25 to 30%
An interesting Observation
Heart Failure: Assynchronous Mechanics:
Normal Sinus Rhythm
Left Bundle Branch Block
Prevalence and Prognosis of Ventricular Dysynchrony LBBB More Prevalent with Impaired LV Systolic Function
Preserved LVSF (1)
Impaired LVSF (1)
Mod/Sev HF (2)
8%
49%
34%
24%
38%
1. Masoudi, et al. JACC 2003;41:217-23 2. Aaronson, et al. Circ 1997;95:2660-7
Doug Smith:
Increased All-Cause Mortality with Wide QRS at 45 Months (3) P < 0.001
QRS < 120 ms
QRS > 120 ms
3. Iuliano et al. AHJ 2002;143:1085-91
Abnormal Ventricular Activation
CRT: Three-chamber Pacing
MIRACLE: 2002 Multi-center In Sync Randomized Clinical Evaluation Trial
Double blinded RCT First US trial NYHA Class III or IV, on OPT, QRS >130 ms, EF150 Acute hemodynamic testing Randomization 1:1
4 weeks
Best single chamber
CRT
8 weeks
No CRT
No CRT
12 weeks
CRT
Best single chamber
One year
Best mode
PATH-CHF
Primary endpoints
Secondary endpoints
Peak VO2 Six-minute walk distance Minnesota Living with Heart Failure score (QOL) NYHA class EF Trend towards decrease in Hospitalizations
Acute hemodynamic testing revealed that the lateral and posterolateral walls were the best target sites.
The best responders were those with QRS>150 , long PR and dP/dt < 700 mm Hg/s
MUSTIC: 2001 Multicenter Stimulation in CM
European study with 67 patients QRS>150, CHF, EF 0.12 sec
Moss AJ. N Engl J Med. 2002;346:877-83.
Conventional Rx n =490
ICD Rx n=742
39% 34% 23% 4%
35% 35% 25% 5% 51%
50%
MADIT-II Patient Characteristics Medications at Last Contact
ACE I Beta Blockers Lipid Lowering Statins
Digitalis Amiodarone Class I AA Moss AJ. N Engl J Med. 2002;346:877-83.
Conventional Rx n =490
ICD Rx n=742
72% 70% 64% 57% 10% 2%
68% 70% 67% 57% 13% 3%
MADIT-II Results
Lead Problems Non-fatal Infections
Heart Failure Hospitalization
Moss AJ. N Engl J Med. 2002;346:877-83.
Conventional Rx n =490
ICD Rx n=742
-
1.8% 0.7%
14.9%
19.9%
MADIT-II Conclusions For post-MI patients with LVEF < 30%:
ICD therapy significantly reduced the incidence of overall mortality by 31%
ICD therapy provided significant benefit among patients who were on optimal drug therapies.
Moss AJ. N Engl J Med. 2002;346:877-83.
MADIT-II Survival Results Probability of Survival
1.0 1.9 Defibrillator 1.8 1.7
Conventional P = 0.007
1.6 0.0 0
1
2
3
4
Year No. At Risk Defibrillator 742 Conventional490 Moss AJ. N Engl J Med. 2002;346:877-83.
502 (0.91) 329 (0.90)
274 (0.94) 170 (0.78)
110 (0.78) 65 (0.69)
9 3
MADIT-II Statistical Analysis Triangular Sequential Design 11/13/01 – Reached efficacy boundary (P = 0.027)
Log-Rank Statistic
20
01/16/02 – Closeout (P=0.016)
10
Efficacy boundary for defibrillator
Boundary indicating no difference between groups
0
Inefficacy boundary for defibrillator
-10
0
20
40
60
Variance
Sequential Monitoring in the Triangular Design Moss AJ. N Engl J Med. 2002;346:877-83.
80
Mortality rate by type of therapy
Mortality rate (%)
MADITT-II, mean follow-up 20 months
20
19.8% (p=0.016)
15
14.2%
10 0 Non-ICD group (n= 490)
A. J. Moss, et al. N Engl J Med 2002;346:877-83.
ICD group (n= 742)
MADIT-II: Survival Results
Moss AJ. N Engl J Med. 2002;346:877-83.
MADIT-II: Survival Results
Moss AJ. N Engl J Med. 2002;346:877-83.
Hospitalizations for heart failure by type of therapy Hospitalization rate (%)
MADITT-II, mean follow-up 20 months
19.9%
20 (p=0.09) 15
14.9%
10 0 Non-ICD group (n= 490)
A. J. Moss, et al. N Engl J Med 2002;346:877-83.
ICD group (n= 742)