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Managing the Patient with Congestive Heart Failure

Javier Jimenez MD PhD FACCDirector, Advanced Heart Failure and

Pulmonary HypertensionMiami Cardiac & Vascular Institute

South Miami Hospital

Speaker Disclosures

• I disclose that I am a Consultant for St Jude Medical.

• I disclose that I am a member of the speaker’s bureaus for Gilead, United Therapeutics, Bayer and Actelion Pharmaceuticals.

• I will not discuss off-label or unapproved usage.

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Objectives

• Discuss common causes of Heart Failure• Review what is an appropriate evaluation

and management of a heart failure patient• Learn about new drug therapies

• Develop strategies to prevent re-hospitalizations

Stages, Phenotypes and Treatment of HF

Etiology of Cardiomyopathy

Cardiomyopathy

Ischemic Non-Ischemic

Primary Cardiomyopathy

MIXED

Dillated Cardiomyopathy

Restrictive-Non hyperthopied

ADQUIRED

Myocarditis

Takotsubo

Peripartum

GENETIC

RVD

HCM

Mytochondrial

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HypertensiveValvular

Drug related: chemo, etohNon Compaction

Amyloid, SarcoidThyroid, DMRA, Lupus

HemochromatosisTuberous Sclerodis

EsosinophylicMELAS

Diagnostic Testing

• Electrocardiography (EKG)• Echocardiography (E)

• Nuclear Imaging (NI)• Angiography (CA)

• Cardiac CT (CCT)• Cardiac MRI (MRI)• Endomyocardial Biopsy (BX)

• Laboratory testing (LAB)

Ischemic Cardiomyopathy What kind of cardiomyopathy

A-HCM NON -OBS

B-HTN CM

D-MUCHOPOLYS

C-AMYLOID

E-OXALOSIS

F-FRIEDIREICH ATX

Non CompactionCardiomyopathy Hyperthrophic Cardiomyopathy

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Cardiac Amyloidosis Arrhythmogenic Right Ventricular Cardiomyopathy

Prognosis depends on Etiology

1230 pts. referred for unexplained CM. Felker GM. NEJM 2000;342:1077

History and Physical Exam in HF

• Clues suggesting etiology of HF• Duration of illness• Severity, triggers and associated symptoms• Weight changes• Palpitations, syncope• Volume status• Disorders breathing at night• Prior hospitalizations for HF• Discontinuation of medications

CASE 1-Initial Evaluation

• 75 year old female• 2 months worsening SOB/orthopnea• Presented to ED after eating at a BBQ

• Past Hx bordeline HTN, COPD, no meds

• Physical exam• HR 98, BP 150/82, RR 28, temp 36.0C• JVP elevated, crackles, pulses 2+, legs

warm and LEE1+

CASE 1-Initial Evaluation

• 74 year old female• CXR = pending

• Labs = pending

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How confident are you that it is AHF?

1. <20%2. 21-40%

3. 41-60%4. 61-80%

5. >80%

No right answer

AHF Dx Scoring systems

Baggish AL, et al. Am Heart J 2006; 151: 48-54].

Predictor Points Our Case

Elevated NT-proBNP 4 ?

Interstitial edema on

CXR2 ?

Orthopnea 2 -

Absence of fever 2 2

Current loop diuretic

use1 -

Age > 75 years 1 -

Rales on lung

examination1 1

Absence of cough 1 1

Interpretation 4

e.g. At a score of 9, PPV 92%, NPV 82%, sens 70, spec 93

CASE-1 More information

• 75 year old female• CXR = increased pulmonary markings c/w

edema, no evidence of COPD• Labs = troponin I 0.20

– BNP 728 pg/ml– Creatinine 1.30

AHF Dx Scoring systems

Baggish AL, et al. Am Heart J 2006; 151: 48-54].

Predictor Points Our Case

Elevated NT-proBNP 4 4

Interstitial edema on

CXR2 2

Orthopnea 2 -

Absence of fever 2 2

Current loop diuretic

use1 -

Age > 75 years 1 -

Rales on lung

examination1 1

Absence of cough 1 1

Interpretation 10

e.g. At a score of 9, PPV 92%, NPV 82%, sens 70, spec 93

Risk Scores to Predict Outcomes in HF

J Am Coll Cardiol. 2013;62(16):e147-e239. doi:10.1016/j.jacc.2013.05.019

-SEATTLE HEART FAILURE MODEL

-HEART FAILURE SURVIVAL SCORE

-CHARM RISK SCORE

-CORONA RISK SCORE

-HPRESERVE SCORE

-ADHERE CLASSIFICATION

-AHA GET WITH THE GUIDELINES

-EFFECT RISK SCORE

-OPTIMIZE HF RISK PREDICTION SCORE

• What is BNP?

– A 32 amino acid polypeptide

– Secreted by cardiac myocytes in response to excessive distension of the Heart ventriclesNamed after extracts found in Pig-brain

• What is NT-proBNP?

– NT-proBNP is a biologically inactive 76 amino acid N-terminal fragment

– Co-secreted with BNP

– Even longer t1/2 than BNP (~1-2hrs vs ~20mins)

• Biological effects of Cardiac Natriuretic peptides

– Increase Natriuresis

– Decrease peripheral vascular resistance

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Recommendation

-Use a validated diagnostic scoring system forpatients in whom the diagnosis of AHF is beingconsidered

-This recommendation places a relatively high valueon evaluating the constellation of clinical findings in apatient with suspected AHF and less value on anindividual physical examination finding, presentingsymptom or investigation.

Recommendation

• In the clinical scenario when the clinical diagnosis of AHF is of intermediate pre-test probability, a BNP level can be obtained

– to rule-out AHF (BNP <100 pg/ml; NT-proBNP <300 pg/ml)

– or rule-in AHF (BNP >500 pg/ml; NT-proBNP>900 pg/ml if age 50-75 years, NT-proBNP>1800 if age >75 years) as the cause for the presenting symptoms suspicious of AHF

Practical Tips

• A precipitating cause for AHF should be sought.

• An ECG and a chest x-ray should be performed within 2 hours of initial presentation.

• Initial blood tests should include: complete blood count, creatinine, blood urea nitrogen, glucose, sodium, potassium, and troponin.

What additional tests should we order?

• A-Echocardiogram• B-Coronary CT angiogram

• C-Nuclear Stress test• D-All of them

Non Invasive testing

• Echocardiogram– Initial CHF presentation– Repeat if change in clinical status

• Nuclear Cardiac Imaging– If suspected myocardial ischemia– Viability

• Cardiac MRI– Viability– Infiltrative cardiomyopathies

Invasive testing

• Hemodynamics– Guide therapy– Impaired perfusion– Assessment volume status

• Coronary Angiography– Suspected ischemia– Planned revascularization

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Practical Tips

• A transthoracic echocardiogram should be performed within 72 hours of presentation.

• For patients with a prior echocardiogram, another is not required unless there has been a significant change in clinical status requiring investigation, a lack of clinical response to appropriate therapy and/or it is greater than 12 months since the prior echocardiogram.

CASE 2-Management of AHF

• 50 year old male with history of congestive heart failure– Presents to ER after the Miami Heat wins the

season• SOB on minimal exertion, orthopnea• HR 105, BP 99/52, RR 24, temp 98.6F• JVP difficult to assess (thick neck)• Crackles both lungs• pulses weak, legs cool and LLEE 1+• Trop: 0.15 Pro-BNP 12,000• CXR=CHF

How much diuretic will you give and how?

1. IV furosemide 20 mg bid2. IV furosemide 40 mg bid

3. IV furosemide 80 mg bid4. IV furosemide 10 mg/hour infusion

5. Other choice

BACKGROUND

• IV loop diuretics are standard on the current treatment of AHF

• Data to guide the use of loop diuretics are sparse.

• Guidelines are based primarily on expert opinion.

• Clinical practice varies widely with regard to both the mode and

dose of administration.

• High doses of loop diuretics may have harmful effects

Activation of the renin–angiotensin and sympathetic systems,

Electrolyte disturbances

Worsening of renal function.

DOSE: Study Design

Acute Heart Failure (1 symptom AND 1 sign)

<24 hours after admission

2x2 factorial randomization

Low Dose (1 x oral)

Q12 IV bolus

48 hours

1) Change to oral diuretics

2) continue current strategy

3) 50% increase in dose

Co-primary endpoints

High Dose (2.5 x oral)

Q12 IV bolus

Low Dose (1x oral)

Continuous infusionHigh Dose (2.5 x oral)

Continuous infusion

72 hours

Clinical endpoints

60 days Felker, NEJM 2011

• Efficacy:– Patient Global Assessment by visual analog

scale over 72 hours using area under the curve

• Safety:– Change in creatinine from baseline to 72

hours

DOSE: Co-Primary Endpoints

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DOSE: patient global assessment DOSE: DOSE: Death, Rehosp

• There was no statistically significant difference in global symptom relief or change in renal function at 72 hours for either:

• bolus vs. infusion or low vs. high

• No clinical differences…but– High was associated with favorable trends:

– Symptom relief (global assessment and dyspnea)– Weight loss and net volume loss– Proportion free from signs of congestion– Reduction in NT-proBNP

DOSE-AHF Conclusions Recommendations: Diuretics

We recommend intravenous diuretics be given as first line therapy for patients with congestion (Strong Recommendation, Moderate Quality Evidence).

We recommend for patients requiring intravenous diuretic therapy, furosemide may be dosed intermittently (e.g. twice daily) or as a continuous infusion (Strong Recommendation, Moderate Quality Evidence).

Diuretic Resistant Patient ??

• Assess volume status• Restrict Na2+/H2O intake

• Add another type of diuretic with different site of action (thiazides, spironolactone).

• Hemodynamic assessment and/or positive inotropic agents.

• Hemodialysis, or ultrafiltration

The patient remains persistently symptomatic with Heart Failure, what is next option?

1. Add digoxin2. Increase ACEI3. Reduce beta blockers4. Add inotropic agent5. Call for help

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Oral vasodilators

• Optimize ACE inhibitors/ARB dosing• Add oral hydralazine

• Add oral nitrates• Add phophodiesterase inhibitors

…but do not worry about low blood pressure

… unless symtomatic

Intravenous Vasodilators

a)Nitroglycerin (Strong Recommendation, Moderate Quality Evidence);

b)Nesiritide (Weak Recommendation, High Quality Evidence);

c)Nitroprusside (Weak Recommendation, Low Quality Evidence).

AHA 2012: RELAX-AHF, CARRESS

Inotropes

• Hemodynamically stable patients do not routinely receive inotropes like dobutamine, dopamine or milrinone (Strong Recommendation, High Quality Evidence).

• Values and Preferences These recommendations for inotropes place high value on the potential harm demonstrated when systematically studied in clinical trials and less value on potential short term hemodynamic effects of inotropes.

• …but they may be very helpful in the appropriate patient specially if you know the hemodynamics

Do I stop the beta-blockers on admission?

• Cohorts suggest continuing beta-blockersadvantageous

• RCT: B-CONVINCED– Keep vs. Stop strategy in known HF pts on

beta-blockers– Keep was non-inferior to Stop.– Does not delay clinical improvement– Predicts staying on BB in the longer term

Eur Heart J 2009; 30:2186-92

Case 3Case 3--Something in the horizonSomething in the horizon

• 65 years old female, previous MI

• Stable NYHA II, LVEF 30-35%. Two recent hospitalizations.

• On optimal dose of lisinopril, and metoprolol, intermediate dose ofdiuretics

• Pt with prior ICD implanted

• BP 99/67 mmHg, HR 85 bpm

• K, 4.7 mEq/L; NT-proBNP1500 pg/mL

• EKG: old anterior MI, LBBB QRS 155 ms.

1.Add an aldostenore inhibitor

2.Upgrade to a BiV ICD3.Leave patient alone since he is FC -2

4.Add digoxin5.Anything else?

Is there anything else you can do?

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NYHA III* or IV heart failureNYHA III* or IV heart failureLVEF LVEF ≤ ≤ ≤ ≤ ≤ ≤ ≤ ≤ 35%35%

ACEACE--I + loop diuretic I + loop diuretic ±± digoxndigoxn

NYHA III* or IV heart failureNYHA III* or IV heart failureLVEF LVEF ≤ ≤ ≤ ≤ ≤ ≤ ≤ ≤ 35%35%

ACEACE--I + loop diuretic I + loop diuretic ±± digoxndigoxn

AldactoneAldactone®® 25 mg/day25 mg/day

(n = 822)(n = 822)

AldactoneAldactone®® 25 mg/day25 mg/day

(n = 822)(n = 822)

Primary EndpointPrimary Endpoint�� Total mortalityTotal mortality

Secondary EndpointSecondary Endpoint�� Cardiac mortalityCardiac mortality�� Cardiac hospitalizationCardiac hospitalization�� Cardiac mortality or cardiac Cardiac mortality or cardiac hospitalizationhospitalization�� Changes from baseline in NYHA classificationChanges from baseline in NYHA classification

Primary EndpointPrimary Endpoint�� Total mortalityTotal mortality

Secondary EndpointSecondary Endpoint�� Cardiac mortalityCardiac mortality�� Cardiac hospitalizationCardiac hospitalization�� Cardiac mortality or cardiac Cardiac mortality or cardiac hospitalizationhospitalization�� Changes from baseline in NYHA classificationChanges from baseline in NYHA classification

PlaceboPlacebo

(n = 841)(n = 841)

PlaceboPlacebo

(n = 841)(n = 841)

Pitt et al, N Engl J Med, 1999.Pitt et al, N Engl J Med, 1999. *History of NYHA IV within 6 months before first dose*History of NYHA IV within 6 months before first dose

3 years3 years

RALES: Study DesignRALES: Study Design RALES-All-Cause Mortality

RALES

Combined Endpoint of Cardiac

Mortality or Cardiac Hospitalization

CRT in Patients with Mild HF Symptoms:MADIT-CRT

Moss et al, NEJM 2009

1820 pts, mostly NYHA II, CRT+ICD vs. ICD aloneLow risk population, annual mortality ~3%40% reduction in HF events in CRT-ICD group

25% reduction in mortality

N Engl J Med. 1997; 336: 525-33

Placebo

(n=3403)

Digoxin

(n=3397)

Absolute

Risk

Difference

Hazard ratio

(95% CI)P value

Heart Failure 35% 27% –8%0.72

(0.66–0.79)<0.001

All-Cause 67% 64% –3%0.92

(0.87–0.98)0.006

Reduces Risk of Hospital Admission (The DIG Trial)

Digoxin significantly reduced the risk of

hospitalization due to heart failure by 28% during

37 months of average follow-up, but its effect on

hospitalization due to all causes was more modest

(a 8% reduction) N Engl J Med. 1997; 336: 525-33

HR = 0.99;

95% CI = 0.91–1.07;

P = 0.80

Does Not Increase Mortality

(The DIG Trial)

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Systolic Heart failure treatment withthe If inhibitor ivabradine Trial

Heart rate at baseline influences the effect of ivabradine on cardiovascular outcomes in chronic heart failure:

Effect of ivabradine on outcomes in patients with

chronic heart failure (LVEF <35%), one hospital

admission for HF within 12 months and HR ≥75

bpm

Betablocker

Mineralocorticoidreceptor

antagonist

Drugs That Reduce Mortality in Heart Failure With Reduced Ejection Fraction

ACEinhibitor

Angiotensinreceptorblocker

Drugs that inhibit the renin-angiotensin system have modest effects on

survival

Based on results of SOLVD-Treatment, CHARM-Alternative,COPERNICUS, MERIT-HF, CIBIS II, RALES and EMPHASIS-HF

10%

20%

30%

40%

0%

% D

ecre

ase

in M

orta

lity

One Enzyme — Neprilysin — DegradesMany Endogenous Vasoactive Peptides

Endogenousvasoactive peptides

(natriuretic peptides, adrenomedullin,bradykinin, substance P,

calcitonin gene-related peptide)

Inactive metabolites

Neprilysin

Neprilysin Inhibition Potentiates Actions of Endogenous Vasoactive Peptides That Counter

Maladaptive Mechanisms in Heart Failure

Endogenousvasoactive peptides

(natriuretic peptides, adrenomedullin,bradykinin, substance P,

calcitonin gene-related peptide)

Inactive metabolites

Neurohormonal activation

Vascular tone

Cardiac fibrosis, hypertrophy

Sodium retention

Neprilysin Neprilysininhibition

LCZ696

LCZ696: Angiotensin Receptor NeprilysinInhibition

Angiotensinreceptor blocker

Inhibition of neprilysin

Prospective comparison of AR NI with ACEI to Determine I mpact on G lobal M ortality and

morbidity in H eart Failure trial (PARADIGM-HF)

SPECIFICALLYSPECIFICALLYSPECIFICALLYSPECIFICALLY DESIGNEDDESIGNEDDESIGNEDDESIGNED TOTOTOTO REPLACEREPLACEREPLACEREPLACE CURRENTCURRENTCURRENTCURRENT USEUSEUSEUSE

OFOFOFOF ACE ACE ACE ACE INHIBITORSINHIBITORSINHIBITORSINHIBITORS ANDANDANDAND ANGIOTENSINANGIOTENSINANGIOTENSINANGIOTENSIN RECEPTORRECEPTORRECEPTORRECEPTOR

BLOCKERSBLOCKERSBLOCKERSBLOCKERS ASASASAS THETHETHETHE CORNERSTONECORNERSTONECORNERSTONECORNERSTONE OFOFOFOF THETHETHETHE

TREATMENTTREATMENTTREATMENTTREATMENT OFOFOFOF HEARTHEARTHEARTHEART FAILUREFAILUREFAILUREFAILURE

Aim of the PARADIGM-HF Trial

LCZ696400 mg daily

Enalapril20 mg daily

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• NYHA class II-IV heart failure

• LV ejection fraction ≤ 40% � 35%

• BNP ≥ 150 (or NT-proBNP ≥ 600), but one-third lower if hospitalized for heart failure within 12 months

• Any use of ACE inhibitor or ARB, but able to tolerate stable dose equivalent to at least enalapril 10 mgdaily for at least 4 weeks

• Guideline-recommended use of beta-blockers and mineralocorticoid receptor antagonists

• Systolic BP ≥ 95 mm Hg, eGFR ≥ 30 ml/min/1.73 m2

and serum K ≤ 5.4 mEq/L at randomization

PARADIGM-HF: Entry Criteria

0

16

32

40

24

8

Enalapril(n=4212)

360 720 10800 180 540 900 1260

Days After Randomization41874212

39223883

36633579

30182922

22572123

15441488

896853

249236

LCZ696Enalapril

Patients at Risk

1117

Kap

lan-

Mei

er E

stim

ate

ofC

umul

ativ

e R

ates

(%

) 914

LCZ696(n=4187)

HR = 0.80 (0.73-0.87)P = 0.0000002

Number needed to treat = 21

PARADIGM-HF: Cardiovascular Death or Heart Failure Hospitalization (Primary Endpoint)

Enalapril(n=4212)

LCZ696(n=4187)

HR = 0.80 (0.71-0.89)P = 0.00004

Number need to treat = 32

Kap

lan-

Mei

er E

stim

ate

ofC

umul

ativ

e R

ates

(%

)

Days After Randomization

41874212

40564051

38913860

32823231

24782410

17161726

1005994

280279

LCZ696Enalapril

Patients at Risk

360 720 10800 180 540 900 12600

16

24

8

693

558

PARADIGM-HF:Cardiovascular Death

10%

Angiotensin Neprilysin Inhibition With LCZ696 Doubles Effect on Cardiovascular Death of Current Inhibitors of the Renin-Angiotensin

System

20%

30%

40%

ACEinhibitor

Angiotensinreceptorblocker

0%

% D

ecre

ase

in M

orta

lity 18%

20%

Effect of ARB vs placebo derived from CHARM-Alternative trialEffect of ACE inhibitor vs placebo derived from SOLVD-Treatment trial

Effect of LCZ696 vs ACE inhibitor derived from PARADIGM-HF trial

Angiotensinneprilysininhibition

15%

Case 4-Rehospitalization 74 year old female with NYHA FC II-III HF with LVEF 20-25%BP 90/70, HR 85, Na 130, Creat 2.1mg/dL, K+ 5.0. Euvolemic , Fith day after admission. Feeling back to her baseline. Third hospital admission in two months. Ready for discharge

What should you do next?

A.Arrange for hospice careB.Start intravenous outpatient inotropesC.Change cardiologistD.Refer to an outpatient heart failure program

Worsening Chronic Heart Failure: The Major Reason for Heart Failure Hospitalizations

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Causes of Hospital Readmission for Congestive Heart Failure

17%

Other19%

Failure to Seek

Care

16%

Inappropriate Rx

Rx Noncompliance

24%

Diet Noncompliance

24%

Annals of Internal Medicine 122:415-21, 1995

Over 2/3 of HF Hospitalizations Preventable

Heart Failure Management Issues

• High Mortality• High re-admission rates

• Poor understanding of disease• Poor Rx adherence

• On-going symptoms• Reduced Quality of Life• More relevant in the Elderly

Medication Adherence Gap

• Cost of medications• Complacency-patient and physician

• Side effects• Lack of understanding

• Infrequent monitoring intervals• Lack of reinforcement

What can we do about it?

• Pt follow up soon after discharge• Medication Reconciliation

• Assessment of volume status• Make your life easy and refer to a heart

failure program

Heart Failure Clinic Team

• Nurse Practitioners• Registered Nurses

• Social work services• Nutritionists

• Pharmacists• Physician Supervising

Heart Failure Clinic TeamMCVI- South Miami Hospital

• Nurse Practitioners• Registered Nurses

• Social work services• Nutritionists

• Pharmacists• Physician Supervising

2,000 patients/year

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0% 0%

10%

0%

5%6%

12%

5%

9%

0% 0%

10%

4%5%

0%0%

0%

2%

0% 0% 0%

3%

0%

4%

0%

5%

10%

15%

20%

25%

Oct-13 Nov-13 Dec-13 Jan-14 Feb-14 Mar-14 Apr-14 May-14 Jun-14 Jul-14 Aug-14 Sep-14

Miami Cardiac & Vascular Institute

South Miami HospitalOctober, 2013 - September, 2014

HF Clinic Education Only Patients HF Clinic Treatment Program

National Readmit Rates = 23%

SMH Readmit Rates = 20%

10/13 Implemented

HF Education

Program

Role of Heart Failure Clinics

– Pre-transplant/ pre LVAD eligibility and work-up– Out-patient chronic parenteral inotropic therapy – Medication titration– Patient education– High risk (CHF) rehabilitation programs– Out patient LVAD chronic care– Volume management (outpatient iv diuretics)– Management of social issues

Role of Primary Care Physician

• High risk CHF Patient identification

• Assessment/modification of underlying etiology

• Promt follow up after discharge

• Medication titration• Patient education• Management of

comorbitiies• Family integration

Summary

• When heart failure cannot be controlled look for unsual etiologies

• Follow the guidelines, learn about new drugs• Discharge the patient in a “euvolemic” state

• If available seek the support of a specialized Heart Failure Clinic