Transcript CHF: Part 2 - Benton Franklin County Medical Society

Success with Heart Failure:
What’s in our medicine bag?
J. Susie Woo MD, FACC
Virginia Mason Cardiology
February 20, 2015
The Problem
• HF is common
– Increasing in prevalence
– Lifetime risk of 20% (1:5) after age 40
• HF is expensive
– Most common cause of hospitalization in pts >65 yo
– 5% of total healthcare budget ($32 billion/yr)
HF is deadly
n=216
20% mortality in 1 year
50% mortality in 5 years
Senni M et al. Circ 1998;98:2282-2289.
Clinical diagnosis
• Based on signs and symptoms of volume overload
– DOE, orthopnea, PND
– Weight gain
– Edema, ascites
Jugular venous pressure
Clear lungs and/or CXR do not exclude heart failure!
Supportive testing
• CXR
• BNP
• Echocardiogram
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HFrEF vs. HFpEF
Dilated or non-dilated
Ischemic vs. non-ischemic
LVH, diastolic function
Valve disease
RV fxn, pulmonary pressures
Volume status
Diagnostic workup
• CMP, CBC, Ca/Mg,
TSH, lipid panel
• ECG
• Stress testing and/or
coronary angiogram
Etiologies
Hypertension
Valvular disease
Coronary disease
Viral myocarditis
Diabetes, Obesity
Toxic (alcohol, cocaine, chemotherapy)
Peripartum, Familial, Idiopathic
Sarcoid, Amyloid, Hypertrophic
Ischemic
nonischemic
Biomarkers
BNP
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Much lower in obese pts
Increased with age
Increased in CKD
Higher in women
Lower in HFpEF
Should not be used in
isolation to adjust diuretics
Troponin
– Can be elevated in
decompensated HF
– Low grade (<2.0)
– Increased in CKD
– Poor prognostic indicator
Classification
Hunt SA et al. JACC 2001;38:2101-13.
Farrell MH et al. JAMA 2002;287:890-7.
Stage A
At risk:
HTN, CAD, DM,
metabolic syndrome,
obesity, cardiotoxins,
family h/o CM
Treat HTN, lipids
Quit smoking
Regular exercise
Avoid alcohol, drugs
ACEI/ARB for
vascular disease or
DM
Stage B
Stage C
Heart disease
no HF symptoms
Heart disease,
prior or current HF
MI, LVH, low EF,
valvular disease
SOB, reduced exercise
tolerance
ACEI/ARB
Beta blockers
Diuretics
Salt restriction
ACEI/ARB
Beta blockers
Aldosterone antag
Digoxin
Nitrates/hydraazine
ICD
CRT
Key points
• Heart failure has established risk factors
• Heart failure can be prevented
• Evolving, dynamic syndrome with symptomatic and
asymptomatic phases
• Morbidity and mortality can be reduced by
treatments specific to stage/class
Pathophysiology
Adapted from Maron & Rocco, 2011.
Neurohormonal Imbalance in HF
Norepinephrine
Angiotensin II
Endothelin
Aldosterone
Vasopressin
Vasoconstriction
Fluid Retention
Fibrosis / remodelling
Tachycardia
ANP
BNP
Nitric Oxide
Bradykinin
Prostaglandins
Vasodilation
Natriuresis/diuresis
SNS suppression
RAAS suppression
Adapted from Rev Cardiovasc Med. 2001;2(suppl 2):S2-S6.
Management of HFrEF
The patient’s role
• Salt restriction (2000 mg / 24 hrs)
• Fluid restriction
• Daily weights
Call for weight increase of 3# in 1 day, total of 5#
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Avoidance of NSAIDs and alcohol
CPAP in those with sleep apnea
Regular physical activity
Medication compliance
Cardiac Rehab
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CMS approved in 2014 for stable symptomatic HFrEF
EF ≤35%, NYHA II-IV
≥6 weeks since last CV hospitalization or procedure
HF-ACTION: decreased all-cause mortality or
hospitalization (adjusted HR 0.89, p=0.03)
O’Connor CM et al., JAMA 2009;301(14):1439-50.
Drugs in our medicine bag
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Diuretics
ACE inhibitors / ARBs
Beta blockers
Hydralazine/nitrates
Digoxin
Aldosterone antagonists
Loop Diuretics
• Furosemide
EQUIVALENT DOSES
– 6 hr half-life
– Variable oral bioavailability
• Torsemide & bumetanide
– Almost 100% bioavailability
• Ethacrynic Acid
– For sulfa-allergic
Furosemide 40 mg po
Furosemide 20 mg IV
Torsemide 20 mg po/IV
Bumetanide 1 mg po/IV
Fear progressive volume
overload over hypotension
and renal insufficiency
Thiazide Synergy
• Useful in refractory volume overload
• May be administered simultaneously with loop
• Hydrochlorothiazide
– Ineffective if GFR < 30 ml/min
• Metolazone
– Avoid daily therapy or long courses of treatment
– Start with 2.5 mg, 2-3 days/wk
• BEWARE OF HYPOKALEMIA, hyponatremia, and
worsening renal function
Jentzer JC et al., JACC 2010;56:1527-34.
ACE-Inhibitors
• Indicated in all patients
with HFrEF (EF ≤40%)
• RAAS suppression
• 30% decrease in
mortality
• 25% decrease in
hospitalization
PEARLS
• More is better
• Dose twice daily for
neurohormonal blockade
• Can uptitrate quickly in pts
with normal renal function
• Caution in pts with Cr>3.0
or K>5.0
Trial
Population
Target dose (mg)
CONSENSUS, 1987
NYHA IV
Enalapril 20 bid
SOLVD, 1991
EF ≤35%, NYHA II-III
Enalapril 10 bid
SAVE, 1992
Post-MI, EF ≤40%
Captopril 50 tid
ARBs
• Second line (for the ACEI intolerant)
• May be as effective as ACEI, not superior
– ELITE, ELITE II, VALIANT, RESOLVD, OPTIMAAL
• Decreases CHF hospitalization and CV death
– Val-HEFT, CHARM
• Losartan 150 mg qd more effective than 50 mg qd
Drug
Initial dose (mg)
Target dose (mg)
4 – 8 qd
32 qd
Losartan
25 – 50 qd
100 – 150 qd
Valsartan
20 – 40 bid
160 - bid
Candesartan
Konstam MA et al., HEALL Investigators, Lancet 2009;374(9704):1840-8.
Nitrate / Hydralazine
Venous and arterial vasodilators
ISDN 10 tid or Imdur 30 qd (goal 120 qd)
Hydralazine 25 tid – qid (goal 100 tid or 75 qid)
V-HeFT I: ISDN-H vs. placebo
• Lower mortality and improved EF in ISDN-H vs. placebo
(26% vs. 34%) at 2 yrs, p<0.03
V-HEFT II: ISDN-H vs. enalapril
• Lower mortality in enalapril vs. ISDN-H (18% vs 25%),
p=0.016
Cohn JN et al. NEJM 1986;314:1547-52 and 1991;325:303-10
Nitrate / hydralazine
• Must be used in combination
• TID dosing is difficult
• Should be used in all AfricanAmericans with symptomatic
HFrEF despite ACEI and BB
(BiDil and the A-HeFT trial)
Mortality
15
n=1050
10.2%
10
6.2%
5
n=54
n=32
0
P=0.02
Placebo
Fixed-dose BiDil
Taylor, AL et al., NEJM 2004;351:2049-57.
Beta-blockers
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SNS inhibition
Slows HF progression, reduces hospitalization;
Improves EF, symptoms and survival in NYHA II-IV CHF
34% decrease in mortality
– U.S. Carvedilol (1996), MERIT-HF (1999), CIBIS II (1999)
• NOT a class effect
Drug
Carvedilol
Carvedilol CR
Metoprolol succinate
Bisoprolol
Initial dose (mg)
Target dose (mg)
3.125 bid
50 bid
10 qd
80 qd
12.5 – 25 qd
200 qd
1.25 qd
10 qd
COMET
metoprolol tartrate
carvedilol
40% vs 34%
p=.0017
Poole-Wilson PA et al. Lancet 2003;362:7-13.
More is better
(and a little is much better than none)
6.
Beta blocker Pearls
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Start only when euvolemic
Double dose every 2 wks until target
Do not hold during a decompensation
Use metoprolol succinate or bisoprolol (β1-selective)
for pts with asthma/RAD or lower BP
• Fear not the asymptomatic bradycardia
Clinical Case
60 yo M with ischemic CM, EF 25-30% on last Echo, presents to clinic
with 1 week of increasing dyspnea, orthopnea and LE edema.
Exam: BP 91/65, HR 92, JVP at 19 cm H20, fine bibasilar crackles,
distant heart sounds with +S3, palpable liver edge, warm extremities
with 1+ pitting LE edema.
Meds: ASA 81 qd, carvedilol 12.5 bid, lisinopril 20 bid, digoxin 0.25
qd, simvastatin 40 qhs, torsemide 50 bid, KCl 40 bid
Labs: Na 132, K 4.4, BUN 38, Cr 2.2 (from baseline 1.5), AST 69, ALT
91, AlkP 105, Tbili 2.4, Dig level 1.2 (reference range 0.5-1.9)
ECG shows NSR 90 bpm, LBBB, and old anterior infarct.
Which medication(s) would you change?
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Carvedilol
Lisinopril
Digoxin
Simvastatin
Torsemide
Digoxin
• Cardiac glycoside: inhibits Na/K pump ,
increases intracellular calcium (inotrope)
• For patients with symptomatic HFrEF
40
34.8
35.1
34.7
26.8
30
20
10
p=0.8
p<0.001
Mortality
HF Hospitalization
0
Digoxin
Placebo
NEJM 1997;336:525-33
Digoxin dose and Mortality
Rathore SS et al., JAMA 2003;289:871-8.
Digoxin Pearls
• Narrow therapeutic window!
• Target level: 0.5-0.9
• Watch for hypokalemia, hypomagnesemia
– Toxicity may occur at lower digoxin levels
• Watch for drug interactions
– Amiodarone, clarithromycin, quinidine
• Typical dose no higher than 0.25 qd
– 0.125 qod – qd if >70 yrs, reduced renal function or
low lean body mass (women)
Clinical Case
60 yo M with ischemic CM, EF 25-30% on last Echo, presents to clinic
with 1 week of increasing dyspnea, orthopnea and LE edema.
Exam: BP 91/65, HR 92, JVP at 19 cm H20, fine bibasilar crackles,
distant heart sounds with +S3, palpable liver edge, warm extremities
with 1+ pitting LE edema.
Meds: ASA 81 qd, carvedilol 12.5 bid, lisinopril 20 bid, digoxin 0.25
qd, simvastatin 40 qhs, torsemide 50 bid, KCl 40 bid
Labs: Na 132, K 4.4, BUN 38, Cr 2.2 (from baseline 1.5), AST 69, ALT
91, AlkP 105, Tbili 2.4, Dig level 1.2 (reference range 0.5-1.9)
ECG shows NSR 90 bpm, LBBB, and old anterior infarct.
Anything other changes to his
treatment regimen?
Aldosterone Antagonists
• Decrease sxs, mortality &
HF hospitalization
• RALES (spironolactone)
– EF <35%, NYHA 3-4
• EPHESUS (eplerenone)
– EF <40% after acute MI
• EMPHASIS-HF (eplerenone)
– EF <35%, NYHA 2
Pitt et al, NEJM 1999;341:709-17 and NEJM 2003;348:1309-21.
Zannad F et al, NEJM 2011;364:11-21.
Aldosterone Antagonist Pearls
• Weak diuretics
• No gynecomastia with eplerenone
AVOIDING HYPERKALEMIA
• Contraindications:
– baseline K >5.0
– baseline Cr >2.5 in men, >2.0 in women (GFR <30)
• Start with 12.5 mg qd (or qod if GFR 30-49)
• Discontinue or decrease potassium supplement
• Chem7 at 1 wk, 1 month, 3 months, q3-6 months
– avoid in the unreliable patient
• Hold for dehydration, diarrhea, or K >5.5
Clinical Case
60 yo M with ischemic CM, EF 25-30% on last Echo, presents to clinic
with 1 week of increasing dyspnea, orthopnea and LE edema.
Exam: BP 91/65, HR 92, JVP at 19 cm H20, fine bibasilar crackles,
distant heart sounds with +S3, palpable liver edge, warm extremities
with 1+ pitting LE edema.
Meds: ASA 81 qd, carvedilol 12.5 bid, lisinopril 20 bid, digoxin 0.25
qd, simvastatin 40 qhs, torsemide 50 bid, KCl 40 bid
Labs: Na 132, K 4.4, BUN 38, Cr 2.2 (from baseline 1.5), AST 69, ALT
91, AlkP 105, Tbili 2.4, Dig level 1.2 (reference range 0.5-1.9)
ECG shows NSR 90 bpm, LBBB, and old anterior infarct.
Devices
• ICD (primary prevention)
– EF ≤35%, NYHA 2-3
– At least 40 days post-MI
– GDMT x 3 months
• CRT (BiV)
– EF ≤35%, NSR, QRS ≥150, NYHA 3-4 on GDMT
– EF ≤35%, NSR, LBBB, QRS ≥120, NYHA 2-4 on GDMT
– EF ≤35%, Afib, if expect 100% pacing
Supplements
• Omega-3 PUFA
– “reasonable in NYHA 2-4 pts with HFrEF or HFpEF to reduce
mortality and CV hospitalization”
– GISSI-HF, n=6975: fish oil 1 g qd vs. placebo
– All-cause mortality 27% vs 29% (p=0.04)
• Coenzyme Q10
– Q-SYMBIO, n=420, NYHA 3-4: CoQ10 100 mg tid vs. placebo
– MACE endpt 15% vs 26% (HR 0.5; p=0.003)
– Low event #s: 18 vs 34 CV deaths (p=0.039)
Yancy CW et al., Circ 2013;128:e240-e327.
GISSI-HF Investigators, Lancet 2008; 372: 1223–30.
Mortensen, SA et al., JACC HF 2014;2:641-9.
LCZ696
LCZ696
• = sacubitril + valsartan moiety
• Inhibitor of neprilysin = endopeptidase that degrades
vasoactive peptides (NPs, adrenomedullin, bradykinin)
p=0.0000004
Progress
+ LCZ696?
Levy WC et al., Circ 2006; 113: 1424-1433.
Final points
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HF is preventable
Always assess volume and symptomatic status
Our medicine bag floweth for HFrEF patients
Remember diet and exercise
Counselling and communication are integral to
preventing morbidity/mortality
HF program at VM
• Multidisciplinary clinic
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2 physicians
2 ARNPs
3 nurses
Pharmacists (ACC)
On-site laboratory
Social worker
Dietician
Palliative care team
EP & cath lab support
[email protected]
Thank you