Management of Systolic vs. Diastolic Heart Failure
Michael Wolk, MD,FACC
Weill-Cornell
Great Wall of China Symposium
October, 2004
Basic concepts…
The clinical syndrome of heart
failure can occur with either
normal or reduced LVEF
Virtually all clinical trials of heart
failure therapies have enrolled
only patients with reduced LVEF
Thus…
Extrapolating recommended therapy for HF with reduced EF to patients with HF and normal EF is not “automatic”
Therapy for HF with Reduced EF
Evidence base for ACEI and beta blocker therapy among the largest and most consistent in medicine
diuretic
digoxin
diuretic
digoxin
ACEI
diuretic
digoxin
ACEI
diuretic
digoxin
ACEI
Beta blocker
diuretic
digoxin
ACEI
Beta blocker
diuretic
digoxin
ACEI
Beta blocker
ARB
SOLVD-T (1991)
RRR 21%
CIBIS-2 (1999)
RRR 33%
CHARM-Added (2003) (Beta-blocker subgroup) RRR 30%
Improving Survival in CHF One-year Mortality
CV Death, MI, or HF by Treatment
Pfeffer, McMurray, Velazquez, et al. N Engl J Med 2003;349
ACE-I in HF - Who and How? HFSA Practice Guidelines 2004
All pts (symptomatic and asymptomatic) with LV systolic dysfunction (LVEF <40%).
ACEI should be monitored closely if serum Cr is >2.0 mg/dl or serum potassium is >5.0 mmol/L.
ACEI should be titrated as tolerated, in conjunction with BBs, to target doses used in clinical trials.
Weight Of Evidence: ?-Blockade
Over 18,000 patients evaluated in long-term placebo-controlled clinical trials
Improvement in cardiac function and symptoms; (equivocal effects on exercise tolerance)
Decrease in all-cause mortality by 30%-35% (P<.0001); effect shown in 5 individual trials
Decrease in combined risk of death and hospitalization by 35%-40% (P<.001); effect shown in 7 individual trials
Effect shown in patients already receiving ACE inhibitors
Therapy for HF with Reduced EF
Lifestyle changes:
Salt restriction
Achieve ideal weight
Pursue regular exercise
Avoid smoking, toxins
Therapy for HF with Reduced EF
General considerations for all patients
Treat reversible ischemia
Manage contributing arrhythmia
WHAT HAVE WE LEARNED ABOUT NESIRITIDE IN CHF?
A simple regimen / predictable effect.
Improves hemodynamics.
Improves symptoms.
Diuretic and natriuretic effect.
Favorable neurohormonal effect
Safer then drugs with inotropic effect (dobutamine, milrinone).
RALES: All-Cause Mortality
Months
Survival
0.45
0.50
0.55
0.60
0.65
0.70
0.75
0.80
0.85
0.90
0.95
1.00
0
3
6
9
12
15
18
21
24
27
30
33
36
Risk reduction 29%
95% CI (18%–39%)
P <0.0001
Spironolactone
Placebo
Pitt, N Engl J Med 1999;XX:YYY.
WHAT HAVE WE LEARNED ABOUT CARDIAC RESYNCHRONIZATION?
Improves symptoms.
Improves exercise tolerance.
Reduces rehospitalizations.
LV reversed remodeling.
Reduces mitral regurgitation.
Mortality-Reduced by 20 %
Cardiac Resynchronization Who Should Get It?
Patients with symptomatic heart failure due to severe LV systolic dysfunction, class II or III, in spite of adequate and maximum medical therapy.
QRS duration of ?130 ms.
CP985319-11
47-Year-Old Male, 6 month follow up
s/p PTCA/Stent and ICD
Mortality Reduction with ICD Treatment
CP1108035-1
%
Secondary
Prevention
Primary
Prevention
Mortality by Intention-to-Treat SCD-HeFT-2004
CP1144766-18
Mortality
Follow-up (mo)
HR 97.5% CI P
Amiodarone vs placebo 1.06 0.86, 1.30 0.529
ICD therapy vs placebo 0.77 0.62, 0.96 0.007
Amiodarone
ICD therapy
Placebo
ICD Indications for Primary Prevention of Sudden Death Ischemic Heart Disease
EF 30% or less
Prior myocardial infarction
Cannot have had a MI within 30 days or CABG/PTCA within 90 days
Proposed CMS covered indication-9/04
ICD Indications for Primary Prevention of Sudden Death Non-Ischemic Heart Disease SCD-HeFT and DEFINITE Trials
EF 30% or less
Cardiomyopathy present >9 months
NYHA Class I-IV
Proposed CMS covered indication-9/04
COMPANION Hypotheses
Biventricular CRT alone decreases combined all-cause mortality and all-cause hospitalization. ICD prevents sudden death
1520 Patients Randomized
Medical vs CRT vs CRT-ICD
Endpoint: All-cause Mortality
ICD Implants Mayo
ICDs/ year
CP985319-12
Year (1985-2003)
“Even the wealthiest nations cannot afford to pay to use every medical advance in any patient who might benefit.”
.
Thomas Bigger, Lancet, 2001
Therapy for HF with Reduced EF
Surgery for some (few) patients:
Transplant
Surgical Ventricular Restoration (MVR)
RESTORE – EF 30 to 40%, JACC - 9/04
“Destination” LVAD ?
HF with Normal EF
40 % of HF patients
Most have no identifiable myocardial disease
Elderly Women
Hypertensive and diabetic
HF with Normal EF
Mortality:
Nearly as profound as for reduced EF
5-8% vs 10-15%
(Gaasch-NEJM, 2004)
Morbidity:
Includes frequent readmissions
22% within 12 weeks
HF with Normal EF - Diagnosis
Physiologic abnormalities may be seen on echo or invasively
IN PRACTICE DIAGNOSIS PRIMARILY CLINICAL
Therapy of HF with Normal EF
In the absence of controlled clinical trials…
MANAGEMENT BASED ON
CONTROL OF
PHYSIOLOGIC FACTORS KNOWN
TO AFFECT VENTRICULAR
RELAXATION
PHYSIOLOGIC FACTORS AFFECTING VENTRICULAR RELAXATION
Blood volume, e.g. Diuretics
Ischemia
Blood pressure-goal lower BP than published guidelines, e.g.-ACE, B Blockers
Therapy of HF with Normal EF FACTORS AFFECTING VENTRICULAR RELAXATION
TACHYCARDIA
Principle: Tachycardia can shorten time available for ventricular filling and coronary perfusion
Therefore: Drugs that slow HR or ventricular response to atrial arrhythmias can relieve symptoms
BETA BLOCKERS
Therapy of HF with Normal EF FACTORS AFFECTING VENTRICULAR RELAXATION
MYOCARDIAL ISCHEMIA
Consider coronary revascularization
in patients with symptomatic or
demonstrable myocardial ischemia
CHARM Program
n=3025
LVEF >40% ACEI treated/not treated
CHARM- “Added”
CHARM- “Preserved”
3 component trials comparing
candesartan to placebo
CHARM- “Alternative”
n=2028
LVEF ￡40% ACEI intolerant
n=2548
LVEF ￡40% ACEI treated
Primary outcome:
CV death or CHF hosp
CHARM-Preserved Investigator-reported CHF Hospitalizations
P=0.014
P=0.017
Patients hospitalized
Hospitalizations
Placebo
Candesartan
Proportion of patients (%)
Number of episodes
HR = 0.85
RRR = 29%
New Approaches to the Patient with Heart Failure
Assessment of LV function
Low LVEF
Ejection fraction ≤40%
Signs/symptoms of
fluid retention
No signs/symptoms of