Management of Chronic Heart Failure€¦ · Heart Failure is a Major and Growing Public Health...

Management of

Chronic Heart Failure

Parag Patel, MD Heart Failure / Mechanical Support / Cardiac Transplant

Division of Transplant

Mayo Clinic Florida

Disclosures

Speaker Audience

No Pertinent Disclosures

Discussing All of Heart Failure in 30 minutes…..

Heart Failure is a Major and Growing

Public Health Problem

5.7 million people with HF in the US

> 915,000 new cases / year

> 300,000 deaths / year

Leading cause for ambulatory visits in the

Medicare population

More dollars are spent for the diagnosis and

treatment of HF than any other diagnosis by

Medicare (2014 cost = 39.2 billion)

American Heart Association 2016 Heart and Stroke Statistical Update

Principles of Chronic HF Management

• Step 1: Assess HF diagnosis, etiology and

prognosis

• Step 2: Optimize behavioral, medical and

device therapy

• Step 3: Consider referral for advanced

management and therapies

Step 1: Assess HF Diagnosis and

Current Clinical Status

Assess cardiac structure and function

Determine etiology of HF

Assess clinical severity

Assess Cardiac Structure and Function

Diastolic (normal EF)

- Poorly studied

- General therapeutic

recommendations

Systolic (low EF)

- Well studied

- Definite therapeutic

recommendations

60% of Patients 40% of Patients


Echo

Cardiac MRI

MUGA

Ventriculography

Step 1: Assess HF diagnosis and current clinical

status



Assess clinical severity

Etiology of Systolic Heart Failure

• CAD (Ischemic)

• Hypertension

• Idiopathic

• Endocrine (Thyroid, Carcinoid, Pheo)

• Valvular

• Toxin: EtOH, Cocaine, Chemotherapy

• Arrhythmia

• Rheumatologic: SLE, Sarcoid, Giant Cell

• Genetic / Familial

• Infectious: HIV, Hepatitis, Chagas

• Peripartum

• Congenital

Etiology of Systolic Heart Failure

• CAD (Ischemic)

• Hypertension

• Idiopathic

• Endocrine (Thyroid, Carcinoid, Pheo)

• Valvular

• Toxin: EtOH, Cocaine, Chemotherapy

• Arrhythmia / Tachycardia induced

• Rheumatologic: SLE, Sarcoid, Giant Cell

• Genetic / Familial

• Infectious: HIV, Hepatitis, Chagas

• Peripartum

• Congenital

Step 1: Assess HF diagnosis and current

clinical status


(systolic or diastolic dysfunction)


Assess clinical severity: Functional

Hemodynamic

Prognostic

NYHA: Functional Assessment

Class I: No symptoms with ordinary activity

Class II: Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, dyspnea, or angina

Class III: Marked limitation of physical activity. Comfortable at rest, but less than ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain

Class IV: Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency may be present even at rest

Yes

Stevenson LW. Eur J Heart Failure 1999;1:251-257

No

Wet (Filling Pressures)

Warm (CO)

Yes

No

Hemodynamic Assessment

Profile A

Yes


No

Profile A Profile B


Warm (CO)

Yes

No


Volume

JVP/JVD

Orthopnea/PND

Hepatomegaly

Edema (legs or abd)

Bendopnea

Yes


No

Profile A Profile B

Profile C


Warm (CO)

Yes

No


CO

Volume

Volume

Narrow Pulse

Pressure

Cool extremities

Sleepy/obtunded

Hypotension

Azotemia

Orthopnea/PND

JVD

Hepatomegaly

Edema

Bendopnea

Yes


No

Profile A Profile B

Profile C Profile L


Warm (CO)

Yes

No


CO CO

Volume

Volume

Narrow Pulse

Pressure

Cool extremities

Sleepy/obtunded

Hypotension

Azotemia

Seattle HF Score: Prognostic Assessment

http://depts.washington.edu/shfm/

Principles of Chronic HF

Management

• Step 1: Assess HF diagnosis and current

clinical status


device therapy



Step 2: Optimize therapies

Behavioral therapy

Medical therapy

Device therapy

Salt and Fluid Compliance

The Importance of Education

Compliance rate when patients . . .

Recall MD advice Don’t recall advice

Medications 91.3% 33.3%

Diet 76.4% 44.2%

Activity 23.6% 15.5%

Smoking cess 40.0% 9.6%

Alcohol cess 40.0% 18.2%

Adapted from Kravitz et al. Arch Int Med 1993;153:1869-78

Home Telemonitoring: Not for all

Adapted from Chaudhry et al. NEJM 2010;363:2301-9

Clinical Endpoints

Telemonitoring

(N = 826)

Usual Care

(n = 827) p

Death or

Readmission 52.3% 51.5% 0.75

Death 11.1% 11.4% 0.88

HF Readmission 27.5% 27.0% 0.81

Hospital Days 7.2 ± 14.6 7.0 ± 14.9 0.27

Step 2: Optimize therapies

Behavioral therapy

Medical therapy

Device therapy

Adapted from Cohn JN. N Engl J Med. 1996;335:490–498.

Pathologic

remodeling

Low ejection

fraction Death

Symptoms:

Dyspnea

Fatigue

Edema

Chronic

heart

failure

• Neurohormonal stimulation

• Endothelial dysfunction

• Myocardial toxicity

• Vasoconstriction

• Renal sodium retention

Arrhythmia

Pump failure

Coronary artery disease

Hypertension

Cardiomyopathy

Valvular Disease

Left ventricular

injury

Pathological Progression of CV Disease

Underlying etiology

in ~ 60% of CHF

Underlying etiology in

~ 40% of CHF

ANP

BNP

Relative-Risk 2 Year Mortality

None - - 35%

ACE Inhibitor 23% 27%

Aldosterone Antag 30% 19%

Beta-Blocker 35% 12%

CRT / ICD 36% 8%

Cumulative risk reduction if all four therapies are used: 77%

Absolute risk reduction: 27%, NNT = 4

Updated from Fonarow GC. Rev Cardiovasc Med. 2000;1:25-33.

Cumulative Impact of Heart Failure

Therapies on Long Term Outcomes

Optimization of Medical Therapy

Systolic HF (EF < 40%)

– ACE-I/ARB (IA)

– Beta Blockers (IA)

– Aldosterone antagonists (IB)

– Hydralazine/Isosorbide dinitrate (IA)

– Diuretics (IC)

– Digoxin (IA/IB)

– Exercise testing and training (1B/C)

Proven

mortality benefit

for EF < 40%

Strength of Recommendation:

IA: Recommended IIB: May be considered

IIA: Responsible III: NOT recommended

Strength of Evidence:

A: Multiple RCT / meta analyses

B: Single RCT / no-randomized studies

C: Expert opinions

NCDR: Improved OMT Over Time

Dodson, JA. Circulation. 2014;129:580-586.

P < 0.01

Control Volume Reduce Mortality

Diuretics

Digoxin

-Blocker ACEI

or ARB

Aldosterone

Antagonist

or ARB

Treat Residual Symptoms

CRT

an ICD*

Hyd/ISDN*

Abraham WT, 2005.


Diuretics

Clinical Pearls

• Use minimal dose needed to maintain

euvolemic state

• Bumex > torsemide > lasix

• Consider metolazone 30 minutes prior to loop

but NOT DAILY

• Daily weights. If weight increases by 3 lbs in 1

day or 5 lbs in 1 week, consider dose

escalation AND reinforce behavioral therapy

• Don’t worry about BP!


Diuretics

Digoxin

-Blocker ACEI

or ARB

Aldosterone

Antagonist

or ARB


CRT

an ICD*

Hyd/ISDN*

Abraham WT, 2005.


ACE Inhibitors (ARBs)

Clinical Pearls

Do not use if Cr ≥ 3 g/dL, bilateral

RAS, K+ ≥ 5.5 mmol/L

Start lowest dose and uptitrate slowly

Order QHS to stagger meds

Check K+ within 2 weeks of each dose

increase

OK to start if asymptomatic

hypotension = “stable baseline”

Beta Blockers

Clinical Pearls Carvedilol, metoprolol succinate, bisoprolol

START LOW AND GO SLOW

OK to decrease ACE-I to allow for more BP

room to uptitrate beta blocker

Do NOT start or uptitrate when there is

significant volume overload or hypovolemia

Avoid if reactive airway disease,

bradycardia, and DM with hypoglycemia

OK to start if asymptomatic hypotension =

“stable baseline” / Stagger BP medications

Aldosterone Antagonists

Clinical Pearls

• Creatinine should be < 2.5 in men or < 2.0 in women

• Potassium should be < 5.0

• Decrease K supplements

• Check K and Cr in: 1w, 1mo for 3 mo, then Q3mo


Diuretics

Digoxin

-Blocker ACEI

or ARB

Aldosterone

Antagonist

or ARB


CRT

an ICD*

Hyd/ISDN*

Abraham WT, 2005.


NON-GUIDELINE

THERAPIES???

Angiotensin-Neprilysin Inhibition

• Neprilysin degrades several vasoactive peptides:

natriuretic peptides, bradykinin, adrenomedullin

• Neprilysin inhibition increases levels of these

substances: countering neurohormonal activation

LCZ696/Entresto

Renin Angiotensin System

Natriuretic Peptide System

HEART FAILURE

LCZ696

Valsartan

Sacubitril

ANP, BNP

Adrenomodullin

Bradykinin

Others

Angiotensin II AT1 receptor

Vasodilatation

Lower BP

Dec Sympathetic Tone

Dec Aldosterone

Natriuresis/Diuresis

Neprilysin

Inactive

Fragments

Paradigm-HF

In comparison with the enalapril,

LCZ696 patients had:

• Fewer ED visits for worsening

HF (HR, 0.66; P<0.01)

• 23% fewer hospitalizations for

worsening HF (P<0.01)

• Less likely to require ICU (18%

risk reduction, P<0.01), IV

inotropes (31% risk reduction,

P<0.01), and LVAD/transplant

(22% risk reduction, P=0.07)

McMurray et al. NEJM 2014;

CV Death

HF Hospitalization

HR 0.80, p<0.01

HR 0.79, p<0.01

Enalapril

Enalapril

LCZ696

LCZ696

LCZ696 (Entresto)

Clinical Pearls

• Start Entresto AFTER OMT in stable OUTPATIENTS

• Entresto is contraindicated WITH ACE-I or ARB

• When switching from ACE-I allow washout period of 36 hrs

• Patients previously taking ACE-I / ARB:

– Starting dose 49/51 mg BID

• Patients not on ACE-I / ARB or previously taking low doses:

– Starting dose 24/26 mg BID

• Double ENTRESTO after 2-4 wks to target dose of 97/103

mg BID

Swedberg et al. Lancet 2010; 376: 875–85

• Ivabradine inhibits the If current in the SA node

• Inclusion criteria • Symptomatic HF and LVEF ≤ 35%

• Sinus Rhythm ≥ 70 bpm

• HF hospitalization previous 12 months

• On stable background therapy including BB when

tolerated

SHIFT Trial: Ivabradine


Ivabradine: Median HR Reduction Over Time

Placebo (n = 3264)

Ivabradine (n= 3241)

Ivabradine: CV Death or Hosp

Admission for Worsening HF


Placebo (n = 3264)

937 events


793 events

RR 18%, p < 0.01


Ivabradine: All Cause Death

Placebo (n = 3264)

552 events


503 events

RR 10%, p = NS


Diuretics

Digoxin

-Blocker ACEI

or ARB

Aldosterone

Antagonist

or ARB


CRT

an ICD*

Hyd/ISDN*

Abraham WT, 2005.


NON-GUIDELINE THERAPIES:

Is it worth the Price?

More meds?


Diuretics

Digoxin

-Blocker ACEI

or ARB

Aldosterone

Antagonist

or ARB


CRT

an ICD*

Hyd/ISDN*

Abraham WT, 2005.


Consideration of Device Therapy Internal Cardio-Defibrillator

(ICD)

– LVEF ≤ 35% (IA)

– Optimized Medical Therapy

– Class II/III with

• Nonischemic cardiomyopathy

• Ischemic cardiomyopathy but no

MI in last 40 days

– LVEF 35-40%: if NSVT and

ischemic, EPS

Cardiac Resynchronization

Therapy (CRT) +/- ICD

– LVEF ≤ 35%

– Optimized Medical Therapy

– Class III/IV with

• QRS ≥120 ms

• NSR (IA) / Afib (IIB)

• High dependence on V-pacing

(IIC)

Invasive Monitoring: OptiVol

OptiVol Threshold

OptiVol Fluid Index:

Accumulation of the

difference between the

Daily and Reference

Impedance

Remote Monitoring: CardioMEMS

Control

Treatment

HR: 0.63

(p < 0.0001)

The Lancet 2011 377, 658-666

Principles of Chronic HF

Management

• Step 1: Assess HF diagnosis and current

clinical status


device therapy



Who Should be Referred to an

Advanced Heart Failure Program?

Who Should be Referred to an

Advanced Heart Failure Program?

• Inability to walk 1 block with shortness of breath

• Requiring inotropic therapy

• Serum Cr > 1.5mg/dL, BUN >40 mg/dL

• Serum Na < 135 mmol/L

• CHF requiring 2 or more admissions in last year

• Inability to uptitrate ACE inhibitor or B-blocker

• Diuretic dose >1.5mg/kg/d

• Severe weight loss (cardiac cachexia)

• Malignant or recurrent ventricular arrhythmias

• Failure to respond to BiV pacing

Left Ventricular Assist Device

Slaughter MS. NEJM 2009; 361:2241-51.

N = 78050

2009 ISHLT Slide Set 2009

ISHLT Registry

Dwight Kroening

Ironman Triathlon

Heart Transplantation Remains Gold-Standard

• Questions? [email protected]

Thank you

MERIT-HF Study Group. Effect of Metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomized

intervention trial in congestive heart failure (MERIT-HF). LANCET. 1999;353:2001-07.

Severity of Heart Failure: Modes of

Death

12%

24%

64%

CHF

Other

Sudden Death

n = 103

NYHA II

26%

15%

59%

CHF

Other

Sudden Death n = 103

NYHA III

56%

11%

33%

CHF

Other

Sudden Death

n = 27

NYHA IV

Quality of Outpatient HF Care: IMPROVE HF

Fonarow GC, et al. Circ Heart Fail. 2008;1:98–106

Elig

ible

patients

with

treatm

ent

(%)

11,271 ÷

14,167

12,039 ÷

14,058

905 ÷

2,505 2,450 ÷

3,533

528 ÷

1,361

3,630 ÷

7,169

9,459 ÷

15,381

Conformity with 7 Performance Measures at Baseline

ACEI/

ARB

Beta-

blocker

Aldos-

terone

Antagonist

Anticoag.

for Atrial

Fib.

ICD HF

Education

N =

Cardiac

Resynch.


Diuretics

Digoxin

-Blocker ACEI

or ARB

Aldosterone

Antagonist

or ARB


CRT

an ICD*

Hyd/ISDN*

Abraham WT, 2005.


Days Since Baseline Visit Date

HYD/ISDN 518 463 407 359 313 251 13

Placebo 532 466 401 340 285 232 24

0 100 200 300 400 500 600 85

90

95

100

P=0.01

Fixed-dose ISDN/HYD

Placebo

Hazard ratio=0.57

Adapted from Taylor AL, et al. N Engl J Med. 2004;351:2049-2057.

43% Decrease in Mortality

A-HeFT: Addition of ISD/HYD to optimized

medications improves mortality in AA

Mortality Reductions with ACE - I

0

5

10

15

20

25

30

Rela

tive R

isk R

ed

ucti

on

(%

)

CONSENSUS SOLVD SAVE AIRE HOPE

n = 253 n = 4228 n = 2231 n = 1986 n = 3577

CONSENSUS: NEJM 1987;316:1429-435, SOLVD: NEJM 1991;325:293-302, SAVE: NEJM 1992;327:669-677

AIRE: Lancet 1993;342:821-828, HOPE: Lancet 2000;355:253-259

Addition of -Blockade to ACE Inhibition Reduces Mortality in Heart Failure

US Carvedilol Trials

Carvedilol (n=696)

Placebo

(n=398)

Days

P<.001

0.0 0 100 200 300 400

65%

1.0

0.8

0.7

0.9

34%

Days

20

15

5

0

10

P=.0062

(adjusted)

Metoprolol CR/XL

(n=1,990)

Placebo

(n=2,001)

MERIT-HF

600 0 400 300 200 100 500

Packer M, et al. N Engl J Med. 1996;334:1349-1355. MERIT-HF Study Group. Lancet. 1999;253:2001-2007.

CIBIS-II Investigators. Lancet. 1999;353:9-13. Packer M, et al. N Engl J Med. 2001;344:1651-1658.

100

90

80

60

70

0

Months

Carvedilol (n=1,156)

Placebo

(n=1,133)

18 0 12 9 6 3 15

35%

P=.0014 (adjusted)

COPERNICUS

Days

0.0

1.0

0.8

0.6

P<.0001

34%

Bisoprolol (n=1,327)

Placebo

(n=1,320)

CIBIS-II

200 400 800 0 600 21

HOPE – Aldosterone Antagonists

indicated in Heart Failure

MI/Stroke/

CV Death

CV Death MI Stroke Total

Mortality

22% Risk Reduction

p<0.001

25% Risk Reduction

p<0.001

20% Risk Reduction

p=<0.001

31% Risk Reduction

p=<0.001

16% Risk

Reduction

p=0.006

N Engl J Med, January 20, 2000

Non CV Death

0% Risk Reduction

p=0.78

Months since randomization

Cu

mu

lati

ve

in

cid

en

ce (

%)

22

0

0 36

2

20

16

18

14

12

10

8

6

4

3 6 9 12 15 18 21 24 27 30 33

Eplerenone

Placebo

RR=0.85 (0.75-0.96) P=0.008

Pitt B, et al. N Engl J Med. 2003;348:1309-1321.

NNT = 50 (1 year)

EPHESUS – Aldosterone Antagonists

indicated post MI with DM or EF ≤ 40


Ivabradine: CHF Death

Placebo (n = 3264)

151 events


113 events

RR 26%, p < 0.01

The High Cost of Heart Failure

AHA

Loss ofProductivity / MortalityLoss ofProductivity / Mortality

Hospital /Nursing CareHospital /Nursing Care

Physicians / OtherProfessionals

Physicians / OtherProfessionals

Drugs / MedicalDurables

Drugs / MedicalDurables

HomeHealth Care

HomeHealth Care

$ 39.2

billion

$3.2

billion

*

$3.4

billion $3.9

billion

$4.1

billion

$24.6

billion

1993 estimated cost = $17.8 billion

2014

The Importance of Education

Adapted from Kollipara et al. Am J Cardio2008:1212-15

ACE Inhibitors

Val-HeFT: ARBs Added to ACE Inhibitors

Improve CHF Hospitalization

Months

Even

t-fr

ee s

urv

ival

(%)

100

0 6 12 18 24

70

80

90 Valsartan

P=0.80

6 12 18 24 0

Valsartan

100

90

80

70

60

Placebo P=0.009

Months

All-Cause Mortality Death or CHF Hospitalization

13%

Placebo

Cohn JN, et al. N Engl J Med. 2001;345:1667-1675.

I IIa IIb III

Classification of Recommendations

Intervention is useful and effective

Weight of evidence/opinion is in

favor of usefulness/efficacy

Usefulness/efficacy is less well established

by evidence/opinion

Intervention is not useful/effective and

may be harmful

Data from many large, RCTs Data from fewer, smaller RCTS, careful analyses of

nonrandomized studies, observational registries

Expert consensus

Level of Evidence

Avoid non-steroidal anti-inflammatory drugs, most anti-

arrhythmic drugs, and most calcium channel blocking

drugs

General Measures

I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III I I I IIa IIa IIa IIb IIb IIb III III III IIa IIa IIa IIb IIb IIb III III III

Stage C Therapy Reduced LVEF with Symptoms

Diuretics and salt restriction are indicated in

patients with current or prior symptoms of HF

and reduced LVEF who have evidence of fluid

retention

Diuretics

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII


Hunt SA, et al. ACC/AHA 2005 Practice Guidelines. Available at: http://www.acc.org.

ACE Inhibitor Recommendations

•Recommended for all patients with current or

prior symptoms of HF and reduced LVEF,

unless contraindicated

• Indicated in all patients with a recent or remote

history of MI regardless of LVEF or presence of HF

•Should be used in patients with a reduced LVEF

and no symptoms of HF, even if they have not

experienced an MI

• Use of 1 of the 3 proven to reduce mortality (ie,

bisoprolol, carvedilol, and sustained release

metoprolol succinate) is recommended for all stable

patients with current or prior symptoms of HF and

reduced LVEF, unless contraindicated

• Indicated in all patients with a recent or remote history

of MI regardless of LVEF or presence of HF

• Indicated in all patients without a history of MI who

have a reduced LVEF with no HF symptoms



-Blocker Recommendations

ARBs approved for the treatment of HF are

recommended in patients with current or prior

symptoms of HF and reduced LVEF who are ACEI-

intolerant

ARBs are reasonable to use as alternatives to ACEIs

as first-line therapy for patients with mild to

moderate HF and reduced LVEF, especially for

patients already taking ARBs for other indications.

Angiotensin Receptor Blockers (ARBs)



Stage C Therapy (Reduced LVEF with Symptoms)

• Reasonable in selected patients with

moderately severe to severe symptoms of

HF and reduced LVEF who can be carefully

monitored for preserved renal function and

normal potassium concentration.* Under

circumstances where monitoring for

hyperkalemia and renal dysfunction is not

anticipated to be feasible, the risks may

outweigh the benefits


*Creatinine ≤2.5 mg/dL in men or ≤2.0 mg/dL in women and K+ <5.0 mEq/L.

Underlining represents changes from 2001 guidelines.


Aldosterone Antagonist

Recommendations

• Addition is reasonable in patients with reduced LVEF

who are already taking an ACEI and -blocker for

symptomatic HF and who have persistent symptoms

• Addition to a standard medical regimen for HF,

including ACEIs and -blockers, is reasonable and can

be effective in blacks with NYHA functional class III or

IV HF. Others may benefit similarly, but this has not

yet been tested

• Might be reasonable in patients with current or prior

symptoms of HF and reduced LVEF who cannot be

given an ACEI or ARB because of drug intolerance,

hypotension, or renal insufficiency

Hunt SA, et al. ACC/AHA 2005 Practice Guidelines. Available at http://www.acc.org.



Combination Hydralazine-Nitrate

Recommendations

Calcium channel blocking drugs are not indicated

Routine combined use of an ACEI, ARB, and

aldosterone antagonist is not recommended for

patients with current or prior symptoms of HF

and reduced LVEF.

Unproven/Not Recommended Drugs and Interventions



Stage C Therapy Reduced LVEF with Symptoms

Stage D Therapy: Patients with Refractory End-Stage HF

Referral of patients with refractory end-stage

HF to an HF program with expertise in the

management of refractory HF is useful.

Referral to an HF Program III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

Stage D Therapy

Referral for cardiac transplantation in

potentially eligible patients is recommended for

patients with refractory end-stage HF

The effectiveness of mitral valve repair or

replacement is not established for severe

secondary mitral regurgitation in refractory

end-stage HF

Surgical Therapy



Medical Therapies for HF

1970 1980 1990 2000

Digoxin

Aldosterone receptor blockers

Vasodilators VA-Coop 19

1982

Nipride

V-HeFT-I

1986

Hdz+I

V-HeFT-II

1991

Hdz+I

V-HeFT-III

1994

ACE+CCB

Val-HeFT

2000

ACE+All

A-HeFT

2000

Hdz+I

ACE-Inhibitors CONSENSUS

1987

Enalapril

SOLVD

1991

Enalapril

32

RC

Trials

HOPE

2000

Ramipril

RADIANCE

1993

DIG

1997

PROVED

1993

RALES

1999

Beta-blockers US Carvedilol

1996

CIBIS-II

1999

MERIT

1999

Copernicus

2001

Ephesus

2003

Angiotensin receptor blockers CHARM

2003

Val-HeFT

2002

1980 1990 2000

Device Therapies for HF

Automatic Implantable

Cardiac Defibrillators

MUSTT

1999

MADIT-II

2002

MADIT

1996

Left Ventricular

Assist Devices

REMATCH

2001

HeartMate

1992

(pneumatic)

Jarvik

1980s

Bi-ventricular Pacing MUSTIC

2001

MIRACLE

2002

PATH-I

1999

HeartMate

1992 (VE)

CONTAK

2002

COMPANION

2003

InSync

2002 Bi-V with ICD

Effect of Post-Discharge HF Management

Cardiologist

Primary care

Home visit

Telephone (PCP or card)

0.125 0.25 0.50 1.00 2.00

Risk Ratio for All Cause Admissions

Whellan DJ. Am Heart J 2005;149(4):722-729

Stage Patient Description

A High risk for

developing HF

• HTN • DM

• CAD • Family history

B

Asymptomatic HF • Previous MI

• LV systolic dysfunction

• Asymptomatic valvular disease

C

Symptomatic HF • Known structural heart disease

• Shortness of breath/fatigue

• Reduced exercise tolerance

D Refractory

end-stage HF

• Marked symptoms at rest

despite maximal medical rx

ACC/AHA Classification: HF Spectrum

Hunt SA et al. J Am Coll Cardiol. 2001


Preserved LVEF HF (EF > 40%)

– Percentage of patients with HFPEF increasing

– Number of admissions for HFPEF is increasing

– Survival is the same as patients with low EF

– Treat known risk factors – HTN, CAD (1A)

– For atrial fibrillation, control resting ventricular rate (IC)

regardless of rhythm (restoration of sinus rhythm IIB/IIC)

– Use diuretics to control congestive symptoms (IC)

– ACE/ARB, BB, Dig, and CCB may be useful IIB/IIC)

Strength of Recommendation:

IA: Recommended IIB: May be considered

IIA: Responsible III: NOT recommended

Strength of Evidence:

A: Multiple RCT / meta analyses

B: Single RCT / no-randomized studies

C: Expert opinions

Anticoagulation Recommendations

Which of the following is the mechanism of action of

a neprilysin inhibitor?

(A) Inhibition of phosphodiesterase-5, resulting in

vasodilation

(B) Inhibition of the funny current in the sinoatrial node,

resulting in decreased heart rate

(C) Inhibition of degradation of endogenous vasoactive

peptides,

including natriuretic peptides, bradykinin, and

adrenomedullin

(D) Increase in the sensitivity of troponin C to calcium,

thus

increasing cardiac contractility without an increase in

intracellular calcium and opening of potassium

channels,

resulting in vasodilation

The PARADIGM trial, which used a neprilysin

inhibitor in combination with an angiotensin receptor

blocker, demonstrated evidence of benefit for

angiotensin receptor-neprilysin inhibition (LCZ696

[valsartan/sacubitril]) compared to enalapril in

patients who have heart failure with reduced

ejection fraction.

An increased risk of which of the following is most

likely to occur as a result of combining an ACE

inhibitor with a neprilysin inhibitor?

(A) Acute renal failure

(B) Angioedema

(C) Dementia

(D) Hyperkalemia

(E) Hypotension

Which of the following patients with systolic heart

failure

would be the best candidate for ivabradine

therapy? (A) A 48-year-old woman with HFrEF , an LVEF of 30%,

NYHA class II, and heart rate of 80 bpm (sinus rhythm), BP

118/72 mm Hg, on a regimen of carvedilol (6.25 mg twice

daily), lisinopril (40 mg daily), and spironolactone (25 mg

daily)

(B) A 59-year-old man with HFrEF, an LVEF of 20%, NYHA

class III, and heart rate of 80 bpm (atrial fibrillation), on a

regimen of metoprolol succinate (100 mg daily), enalapril (20

mg twice daily), and eplerenone (25 mg daily)

(C) A 63-year-old man with HFrEF, an LVEF of 15%, NYHA

class IV , and heart rate of 60 bpm (A-V paced; pacemaker-

dependent), on a regimen of metoprolol tartrate (12.5 mg

twice daily), spironolactone (25 mg daily), torsemide (40 mg

twice daily)

(D) A 62-year-old woman with HFrEF. an LVEF of 25%, NYHA

class III, and heart rate of 76 bpm (sinus rhythm), BP 108/68

mm Hg, on a regimen of carvedilol (25 mg twice daily),

lisinopril (20 mg daily), and furosemide (40 mg daily)

Effect of Ivabradine on LV Remodeling and

Function

Tardif et al. ESC EHJ 2011

54

56

58

60

62

64

66

Ivabradine Placebo

Baseline

Month 8

LVESVI ml/m2

P= 0.0002

7.0 ml/m2

Baseline Baseline 8

mos

8

mos

Effect of Ivabradine on LV Remodeling and

Function

Tardif et al. ESC EHJ 2011

29.5

30

30.5

31

31.5

32

32.5

33

33.5

34

34.5

35

Ivabradine Placebo

Baseline

Month 8

LVEF %

P=

0.0003

2.4

Baseline Baseline 8 mos 8 mos

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