Heart Failure Update: A Device Perspective

Heart Failure Update: A Device Perspective James L. Cockrell, Jr., MD Founding Director, Cardiac Electrophysiology Washington Adventist Hospital April...
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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)

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