The Heart Failure Puzzle: A Picture to be Assembled

1
The Heart Failure PuzzleA Picture to be
Assembled

• Sharon A. Hunt, M.D.
• Professor, Cardiovascular Medicine
• Stanford University
• HEART FAILURE PREVENTION AND MANAGEMENT FROM
  DRUGS TO DEVICES
• Genova, 1-2 Abrile 2005

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HEART FAILURE A PURELY CLINICAL SYNDROME

• Cardinal manifestations
• Dyspnea
• Fatigue/exercise intolerance
• Fluid retention
• (In varying proportions
• in individual patients)

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Heart Failure Scope of the Problem

• Affects 4.8 million Americans1
• Leading cause of hospitalization for people aged
  65 years and older1
• Annual incidence 5,50,000 new cases2
• Lifetime risk 1 in 5 for both men and women1

1. Lloyd-Jones et al. Circulation.
20021063068-3072. 2. Levy et al. N Engl J
Med. 20023471397-1402.
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Heart FailureScope of the Problem

• Significant impact on health economics 24.3
  billion cost per year in the USA
• High prevalence of isolated diastolic HF among
  patients with clinical CHF
• Reported to be as high as 50 to 60
• Euro Heart Survey 63 of patients with clinical
  CHF had an ejection fraction above 40

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HEART FAILURE A PURELY CLINICAL SYNDROME

• Because not all patients have volume overload at
  a given time
• The term heart failure is now preferred over
  the old term congestive heart failure.

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HEART FAILURE A PURELY CLINICAL SYNDROME

• There is no single diagnostic test for the
  syndrome
• No matter what advocates of measuring BNP may say

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HEART FAILURE A PURELY CLINICAL SYNDROME

• May result from disorders of
• Pericardium
• Myocardium
• Endocardium/valves
• Great vessels

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HEART FAILURE A PURELY CLINICAL SYNDROME

• The majority, however, have impairment of LV
  myocardial function

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HEART FAILURE A PURELY CLINICAL SYNDROME

• The majority, however, have impairment of LV
  myocardial function
• With a wide spectrum of functional abnormalities

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Functional abnormalities can range from

• Normal LV size and preserved LV function to
• Severe LV dilatation and markedly reduced LV
  function
• IN MOST PATIENTS ABNORMALITIES OF SYSTOLIC AND
  DIASTOLIC DYSFUNCTION COEXIST

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MAJOR CAUSES OF HEART FAILURE IN THE DEVELOPED
WORLD

• Coronary artery disease
• Hypertension
• Dilated cardiomyopathy (30 genetic)

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Heart failure with preserved systolic function
(PSF)

• has been very under-appreciated in the past
• patients excluded from all previous clinical
  trials

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Prevalence of Heart Failure
Finland (Helsinki)
10
Proportion with decreasedLV systolic
function Proportion with preservedLV systolic
function
9
8
7
6
8.2
5
prevalence
4
3
2
1
4.2
0

age range mean age
66-103 78
75 75
gt 50 -
gt 40 60
55-95 65
75-86 -
70-84 76
gt25 68
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Prevalence of Heart Failure with Preserved EF
78
80
EF? 45
57
60
51
43
EF? 50
EF? 50
Percent of Patients
35
40
EF? 50
EF? 50
20
0
Framingham (N73)
Olmstead (N137)
CHS Prevalence (N269)
NHF Project (N6,700)
CHS Incidence (N597)
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Proportion of Women with Heart Failure and
Preserved EF
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Proportion of Patients with HF-PSF with History
of Hypertension
More patients with HF-PSF are hypertensive at the
time of presentation. More have prior and
current LVH.
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Proportion of Patients with HF-PSF with MI
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OUTCOMES IN PATIENTS WITH HF-PSF

• ARE PROBABLY SOMEWHAT
• MORE BENIGN

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Mortality of Incident HF in CHS
160
140
120
100
Deaths per 1,000 Person-Years
80
60
40
20
0
Low EF No CHF
Low EF CHF
Intact EF No HF
Intact EF CHF
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1-year Outcomes in HF-PSF
Dauterman et al J Cardiac Failure 2001
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Mortality in DIG Study
35.1
23.4
Mean follow-up 37 mos
N496
N3397
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Hospitalizations in DIG Study
66.5 admitted 1.9 admit/pt
67.1 admitted 1.5 admit/patient
Mean follow-up 37 months
N496
N3397
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Morphologic changesHS-PSF vs Systolic HF
HF-PSF
Systolic HF
Normal
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LVH Causative Factors
Hemodynamic load Volume?? Pressure?
Genetic/ environmental factors Age Gender Race O
ther illness
Trophic factors Angiotensin II Aldosterone Catech
olamines Insulin
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Progression from Hypertension to HF
Systolic dysfunction
Smoking Dyslipidemia Diabetes
MI
Heart failure
Death
HTN
Diastolic dysfunction
Obesity Diabetes
LVH
Normal LV Subclinical
Clinical heart LV structure
remodeling LV dysfunction
failure function
Years
Years/months
Adapted from Vasan RS et al. Arch Intern Med.
1996,1561789-1796.
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Differences and Similarities Between HF-PSF and
Reduced EF Heart Failure

• Differences
• Older
• More women
• Less CAD and MI
• More hypertension
• Smaller, thicker LV

• Similarities
• Race
• Diabetes
• Smoking
• Lipids
• Weight
• AF

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TREATING DIASTOLIC HEART FAILURE

• THE THEORY hundreds of papers!
• THE EVIDENCE virtually none!!

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Prevention of Heart Failure in SHEP
8
RR0.51 95 CI 0.37-0.71 Plt0.001
6
4.4
4
Incidence of Heart Failure ()
2.3
2
0
Placebo
Active Rx (Diuretic/BB)
Kostis JB et al. JAMA. 1997278212-216.
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Management of HF-PSFESC guidelines

• No treatment has official indication to date
• Therapeutic guidelines of the ESC
•   ...largely speculative, as limited data exist
  in patients with preserved LV systolic function
  or diastolic dysfunction (level of evidence C),
  patients being excluded from nearly all large
  controlled trials in heart failure.. 

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Management of HF-PSFACC/AHA guidelines

• Recommendations for Management of Heart Failure
  and Preserved Systolic Function
• Class I
• Control BP (Level of Evidence A)
• Control of ventricular rate in patients with AF.
  (C)
• Diuretics to control pulmonary congestion and
  peripheral edema. (C)

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Management of HF-PSFACC/AHA guidelines

• Recommendations for Management of Heart Failure
  and Preserved Systolic Function
• Class IIa
• Coronary revascularization in patients with CAD
  and effect on diastolic function. (C)
• Class IIb
• Restoration of sinus rhythm in patients with AF
  . (C)
• Use of BB,ACEI, ARB, or CCB in patients with
  controlled hypertension to minimize symptoms of
  heart failure. (C)
• Digitalis to minimize symptoms of heart failure.
  (C)