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New Advances in the Diagnosis and Management of Acute and Chronic

Heart Failure

Deborah Budge, MD Intermountain Healthcare Heart Failure Cardiologist

Objectives: • State the updates from the ACC 2013 HF Guidelines • Describe guideline-directed medical therapy for HF

with reduced EF • Understand the mechanism of action of a new therapy

for HF and the results of the initial study

Deborah Budge, MD

Updates in Heart Failure

ACC/AHA 2013 Guideline Update &

PARADIGM

• ~ 6 million symptomatic patients, estimated 10 million in 2037

• Incidence: About 550,000 new cases/year

• More deaths from heart failure than from all forms of cancer combined

• Prevalence is 1% between the ages of 50 and 59, progressively increasing to >10% over age 80

• Over $35 billion/year (5% to 7% of total health care cost)

American Heart Association. 2012 Heart Disease and Stroke Statistical Update.

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Heart Failure in the US

Definition of Heart Failure Classification Ejection

Fraction Description

I. Heart Failure with Reduced Ejection Fraction (HFrEF)

≤ 40% Also referred to as systolic HF. Randomized clinical trials have mainly enrolled patients with HFrEF and it is only in these patients that efficacious therapies have been demonstrated to date.

II. Heart Failure with Preserved Ejection Fraction (HFpEF)

≥ 50% Also referred to as diastolic HF. Several different criteria have been used to further define HFpEF. The diagnosis of HFpEF is challenging because it is largely one of excluding other potential noncardiac causes of symptoms suggestive of HF. To date, efficacious therapies have not been identified.

a. HFpEF, Borderline

41% to 49%

These patients fall into a borderline or intermediate group. Their characteristics, treatment patterns, and outcomes appear similar to those of patient with HFpEF.

b. HFpEF, Improved > 40% It has been recognized that a subset of patients with HFpEF previously had HFrEF. These patients with improvement or recovery in EF may be clinically distinct from those with persistently preserved or reduced EF. Further research is needed to better characterize these patients.

Yancy CW et al. Circulation. 2013;128:e240-e327.

New Approach to the Classification of Heart Failure

• Marked symptoms at rest despite maximal medical therapy (eg, those who are recurrently hospitalized or cannot be discharged from the hospital without specialized interventions)

Refractory end-stage HF D

• Known structural heart disease • Shortness of breath and fatigue • Reduced exercise tolerance

Symptomatic HF C

• Previous MI • LV systolic dysfunction • Asymptomatic valvular disease

Asymptomatic HF B

• Hypertension • CAD • Diabetes mellitus • Family history of cardiomyopathy

High risk for developing heart failure (HF) A

Patient Description Stage

Modified from Jessup M. et al. Circulation.2009

Classification of Heart Failure ACC/AHA Stage and NYHA Class

ACC/AHA HF Stage1 NYHA Functional Class2 A At high risk for heart failure but without structural heart disease or symptoms of heart failure (eg, patients with HTN or coronary artery disease)

B Structural heart disease but without symptoms of heart failure

C Structural heart disease with prior or current symptoms of heart failure

D Refractory heart failure requiring specialized interventions

I Asymptomatic

II Symptomatic with moderate exertion

IV Symptomatic at rest

III Symptomatic with minimal exertion

None

Jessup M. et al. Circulation.2009 New York Heart Association/Little Brown and Company, 1964. Adapted from: Farrell MH et al.JAMA.2002.

Stage A

Diabetes Hypertension

Obesity Atherosclerosis

Stage B

MI Asymptomatic

systolic/diastolic dysfunction

Asymptomatic valvular disease

Stage C

Symptomatic HF Stage D

Advanced HF

590,000

480,000

49,000

4,900

Heart Failure Prevalence by Stage,

Utah*

*Estimates. Go AS, et al. Heart Disease and Stroke Statistics-2013 Update. Circulation 2013;127:e6-e245.

Utah Department of Health. The Impact of Heart Disease and Stroke in Utah 2012.

Stages, Phenotypes and Treatment of HF

STAGE AAt high risk for HF but without structural heart

disease or symptoms of HF

STAGE BStructural heart disease

but without signs or symptoms of HF

THERAPYGoals• Control symptoms• Improve HRQOL• Prevent hospitalization• Prevent mortality

Strategies• Identification of comorbidities

Treatment• Diuresis to relieve symptoms

of congestion• Follow guideline driven

indications for comorbidities, e.g., HTN, AF, CAD, DM

• Revascularization or valvular surgery as appropriate

STAGE CStructural heart disease

with prior or current symptoms of HF

THERAPYGoals• Control symptoms• Patient education• Prevent hospitalization• Prevent mortality

Drugs for routine use• Diuretics for fluid retention• ACEI or ARB• Beta blockers• Aldosterone antagonists

Drugs for use in selected patients• Hydralazine/isosorbide dinitrate• ACEI and ARB• Digoxin

In selected patients• CRT• ICD• Revascularization or valvular

surgery as appropriate

STAGE DRefractory HF

THERAPYGoals• Prevent HF symptoms• Prevent further cardiac

remodeling

Drugs• ACEI or ARB as

appropriate • Beta blockers as

appropriate

In selected patients• ICD• Revascularization or

valvular surgery as appropriate

e.g., Patients with:• Known structural heart disease and• HF signs and symptoms

HFpEF HFrEF

THERAPYGoals• Heart healthy lifestyle• Prevent vascular,

coronary disease• Prevent LV structural

abnormalities

Drugs• ACEI or ARB in

appropriate patients for vascular disease or DM

• Statins as appropriate

THERAPYGoals• Control symptoms• Improve HRQOL• Reduce hospital

readmissions• Establish patient’s end-

of-life goals

Options• Advanced care

measures• Heart transplant• Chronic inotropes• Temporary or permanent

MCS• Experimental surgery or

drugs• Palliative care and

hospice• ICD deactivation

Refractory symptoms of HF at rest, despite GDMT

At Risk for Heart Failure Heart Failure

e.g., Patients with:• Marked HF symptoms at

rest • Recurrent hospitalizations

despite GDMT

e.g., Patients with:• Previous MI• LV remodeling including

LVH and low EF• Asymptomatic valvular

disease

e.g., Patients with:• HTN• Atherosclerotic disease• DM• Obesity• Metabolic syndrome orPatients• Using cardiotoxins• With family history of

cardiomyopathy

Development of symptoms of HFStructural heart

disease


Area New Changes (2013) Format • Practical system

• Guideline-directed medical therapy (GDMT) • Harmonization with other guidelines, consensus documents

Content • Role of validated risk scores • Role of biomarkers

Oral pharmacologic treatment •Broader indications for aldosterone antagonists (mild to moderate HF)

Non-pharmacological interventions • Emphasis on education and transition of care • Balanced approach to Na restriction

Device therapy • Broader indications for CRT • No change for ICDs

Mechanical circulatory support • Class IIa indication for BTT, BTR, DT

ADHF • Loop diuretics – 1st-line therapy • Class IIb – low-dose dopamine • Class II – vasodilators

Recommendations COR LOE ICD therapy is recommended for primary prevention of SCD in selected patients with HFrEF at least 40 days post-MI with LVEF ≤35%, and NYHA class II or III symptoms on chronic GDMT, who are expected to live ≥1 year*

I A

CRT is indicated for patients who have LVEF ≤35%, sinus rhythm, LBBB with a QRS ≥150 ms

I

A (NYHA class III/IV) B (NYHA class II)

ICD therapy is recommended for primary prevention of SCD in selected patients with HFrEF at least 40 days post-MI with LVEF ≤30%, and NYHA class I symptoms while receiving GDMT, who are expected to live ≥1 year*

I B

CRT can be useful for patients who have LVEF ≤35%, sinus rhythm, a non-LBBB pattern with a QRS ≥150 ms, and NYHA class III/ambulatory class IV symptoms on GDMT.

IIa A

CRT can be useful for patients who have LVEF ≤35%, sinus rhythm, LBBB with a QRS 120 to 149 ms, and NYHA class II, III or ambulatory IV symptoms on GDMT

IIa

B

CRT can be useful in patients with AF and LVEF ≤35% on GDMT if a) the patient requires ventricular pacing or otherwise meets CRT criteria and b) AV nodal ablation or rate control allows near 100% ventricular pacing with CRT

IIa B

Practical System

Patient with cardiomyopathy on GDMT for >3 mo or on GDMT and >40 d after MI, or with implantation of pacing or defibrillation device for special indications

LVEF <35%

Evaluate general health statusComorbidities and/or frailty

limit survival with good functional capacity to <1 y

Continue GDMT without implanted device

Acceptable noncardiac health

Evaluate NYHA clinical status

NYHA class I

• LVEF ≤30%• QRS ≥150 ms• LBBB pattern• Ischemic

cardiomyopathy• QRS ≤150 ms• Non-LBBB pattern

NYHA class II

• LVEF ≤35%• QRS 120-149 ms• LBBB pattern• Sinus rhythm

• QRS ≤150 ms• Non-LBBB pattern

• LVEF ≤35%• QRS ≥150 ms• LBBB pattern• Sinus rhythm

• LVEF ≤35%• QRS ≥150 ms• Non-LBBB pattern• Sinus rhythm

Colors correspond to the class of recommendations in the ACCF/AHA Table 1.

Benefit for NYHA class I and II patients has only been shown in CRT-D trials, and while patients may not experience immediate symptomatic benefit, late remodeling may be avoided along with long-term HF consequences. There are no trials that support CRT-pacing (without ICD) in NYHA class I and II patients. Thus, it is anticipated these patients would receive CRT-D unless clinical reasons or personal wishes make CRT-pacing more appropriate. In patients who are NYHA class III and ambulatory class IV, CRT-D may be chosen but clinical reasons and personal wishes may make CRT-pacing appropriate to improve symptoms and quality of life when an ICD is not expected to produce meaningful benefit in survival.

NYHA class III & Ambulatory class IV


• LVEF ≤35%• QRS 120-149 ms• Non-LBBB pattern• Sinus rhythm


• LVEF≤35%• QRS ≥150 ms• Non-LBBB pattern• Sinus rhythm

• Anticipated to require frequent ventricular pacing (>40%)

• Atrial fibrillation, if ventricular pacing is required and rate control will result in near 100% ventricular pacing with CRT

Special CRT Indications

Practical System









Represents optimal medical therapy as defined by the

ACCF/AHA guideline- recommended therapies

(primarily Class I)

Potential benefits of using risk scoring in HF: - Enables patients and families to have a

realistic expectation of prognosis - Promotes open communication between

clinicians, patients, and families to define goals of therapy

- Enables selection of therapies most likely to positively affect the quality and quantity of life

- Enables appropriate allocation of resources, including transplant, MCS, and ICD

Goldberg LR, Jessup M. Circulation 2007;116(4):360.

Risk Scoring

Risk Scores to Predict Outcomes in HF Risk Score Reference (from full-text guideline)/Link

Chronic HF All patients with chronic HF Seattle Heart Failure Model (204) / http://SeattleHeartFailureModel.org

Heart Failure Survival Score (200) / http://handheld.softpedia.com/get/Health/Calculator/HFSS-Calc-37354.shtml

CHARM Risk Score (207) CORONA Risk Score (208)

Specific to chronic HFpEF I-PRESERVE Score (202)

Acutely Decompensated HF ADHERE Classification and Regression Tree (CART) Model

(201)

American Heart Association Get With the Guidelines Score

(206) / http://www.heart.org/HEARTORG/HealthcareProfessional/GetWithTheGuidelinesHFStroke/GetWithTheGuidelinesHeartFailureHomePage/Get-With-The-Guidelines-Heart-Failure-Home- %20Page_UCM_306087_SubHomePage.jsp

EFFECT Risk Score (203) / http://www.ccort.ca/Research/CHFRiskModel.aspx

ESCAPE Risk Model and Discharge Score (215)

OPTIMIZE HF Risk-Prediction Nomogram

(216)


http://seattleheartfailuremodel.org/

http://handheld.softpedia.com/get/Health/Calculator/HFSS-Calc-37354.shtml

http://handheld.softpedia.com/get/Health/Calculator/HFSS-Calc-37354.shtml

http://www.heart.org/HEARTORG/HealthcareProfessional/GetWithTheGuidelinesHFStroke/GetWithTheGuidelinesHeartFailureHomePage/Get-With-The-Guidelines-Heart-Failure-Home-%20%20Page_UCM_306087_SubHomePage.jsp



http://www.ccort.ca/Research/CHFRiskModel.aspx

Seattle Heart Failure Model (SHFM)

Validated multivariable risk scores can be useful to estimate subsequent risk of mortality in ambulatory or hospitalized patients with HF.

I IIa IIb III

Risk Scoring

Natriuretic peptides: mechanisms

UpToDate

Initial diagnosis Prognosis Chronic management in the outpatient

setting

Use of Natriuretic Peptides in Chronic Heart Failure

32%

9%

Natriuretic Peptides and Prognosis in Chronic Heart Failure

Masson S, et al. Clin Chem 2006;52:1528-38 theHeart.org

Measurement of BNP or NT-proBNP is useful for establishing prognosis or disease severity in chronic HF.

I IIa IIb III


Initial diagnosis Prognosis Chronic management in the outpatient

setting


76-year-old man with ischemic cardiomyopathy, LVEF 25%, seen in clinic for routine evaluation

Admitted for decompensated heart failure 4 months ago, uneventful

hospitalization Reports NYHA Class II symptoms, denies congestive symptoms, says he

‘feels great’ Medications: carvedilol 12.5 mg BID, lisinopril 10 mg QD, furosemide 40

mg QD PE: BP 110/62, HR 66, JVP 6 cm, lungs clear, grade 2 MR murmur,

trace edema Labs: creatinine 1.4 mg/dL, BNP 329

Patient Example

Therapeutic inertia Differentiation responders vs non-responders Knowing if a patient is truly maximized on meds Assessing volume status Monitoring those who are ostensibly stable for

impending complications

Challenges with GDMT

Therapies which alter BNP levels

Therapy BNP Level

Diuresis

ACE-I

ARB

Beta-Blockers

Aldosterone Antagonists

CRT

Exercise

Rate control of AF

Serial NP Measurements for Prognostication in Chronic HF

Masson S, et al. J Am Coll Cardiol 2008;52:997-1003 theHeart.org

Understanding Heterogeneous Results in ‘Guided Therapy’ Trials

Motiwala SR, et al. Clin Pharm Ther 2013;93:57-67. theHeart.org

Objective: To compare a strategy of medical therapy titration aimed at achieving and maintaining an NT-proBNP target of < 1000 pg/mL (biomarker-guided therapy) to usual care in high risk patients with HFrEF

BNP- or NT-proBNP guided HF therapy can be useful to achieve optimal dosing of GDMT in select clinically euvolemic patients followed in a well-structured HF disease management program. The usefulness of serial measurement of BNP or NT-proBNP to reduce hospitalization or mortality in patients with HF is not well established.

I IIa IIb III

I IIa IIb III


Aldosterone Antagonist: Mechanism of Action

RALES

NEJM 1999;341:709-17. Cardiosource.com

EPHESUS


EMPHASIS-HF


Aldosterone receptor antagonists are recommended in patients with NYHA class II-IV and who have LVEF of 35% or less, unless contraindicated, to reduce morbidity and mortality. Patients with NYHA class II should have a history of prior cardiovascular hospitalization or elevated plasma natriuretic peptide levels to be considered for aldosterone receptor antagonists. Aldosterone receptor antagonists are recommended to reduce morbidity and mortality following an acute MI in patients who have LVEF of 40% or less who develop symptoms of HF or who have a history of diabetes mellitus, unless contraindicated.

I IIa IIb III


I IIa IIb III

Creatinine should be 2.5 mg/dL or less in men or 2.0 mg/dL or less in women (or estimated glomerular filtration rate >30 mL/min/1.73m2) and potassium should be less than 5.0 mEq/L. Careful monitoring of potassium, renal function, and diuretic dosing should be performed at initiation and closely followed thereafter to minimize risk of hyperkalemia and renal insufficiency.


I IIa IIb III

Check potassium and renal function: - 2 to 3 days after starting therapy - 1 week after starting therapy, AND - At least monthly for the first 3

months

Fonarow G C et al. Circulation 2010;122:585-596

IMPROVE-HF

Pharmacologic Treatment for Stage C HFrEF HFrEF Stage C

NYHA Class I – IVTreatment:

For NYHA class II-IV patients. Provided estimated creatinine

>30 mL/min and K+ <5.0 mEq/dL

For persistently symptomatic African Americans, NYHA class III-IV

Class I, LOE AACEI or ARB AND

Beta Blocker

Class I, LOE CLoop Diuretics

Class I, LOE AHydral-Nitrates

Class I, LOE AAldosterone Antagonist

AddAdd Add

For all volume overload, NYHA class II-IV patients


Strategies for Achieving Optimal GDMT





Non-pharmacological interventions

• Emphasis on education and transition of care • Balanced approach to Na restriction




#1 reason for hospitalization for people >65 years of age

National 30 day readmission rate 25% Mortality 50% at 5 years, 34% at 1 year

following a hospitalization ‘Many HF hospitalizations are driven by gaps in

the process of care rather than worsening pathophysiology’

Need for Improved Care Coordination

Collins SP, et al. J Am Coll Cardiol 2013;61:121-6.

Throughout the hospitalization as appropriate, before hospital discharge, at the first postdischarge visit, and in subsequent follow-up visits, the following should be addressed:

a. initiation of GDMT if not previously established and not contraindicated; b. precipitant causes of HF, barriers to optimal care transitions, and limitations in postdischarge support; c. assessment of volume status and supine/upright hypotension with adjustment of HF therapy, as appropriate; d. titration and optimization of chronic oral HF therapy; e. assessment of renal function and electrolytes, where appropriate; f. assessment and management of comorbid conditions; g. reinforcement of HF education, self-care, emergency plans, and need for adherence; and h. consideration for palliative care or hospice care in selected patients.

I IIa IIb III

Transitions of Care

Of the patients in Utah with HF, 87% have 3 or more chronic conditions, and

54% have 5 or more chronic conditions.

Multidisciplinary HF disease-management programs are recommended for patients at high risk for hospital readmission, to facilitate the implementation of GDMT, to address different barriers to behavioral change, and to reduce the risk of subsequent rehospitalization for HF. Scheduling an early follow-up visit (within 7 to 14 days) and early telephone follow-up (within 3 days) of hospital discharge is reasonable. Use of clinical risk prediction tools and/or biomarkers to identify patients at higher risk for postdischarge clinical events is reasonable.

I IIa IIb III

I IIa IIb III

I IIa IIb III

Transitions of Care

Mixed data evaluating sodium restriction in HF Observational data = association between

sodium intake and risk for hospitalization RCTs = lower sodium intake is associated

with worse outcomes in HFrEF No study has been done in optimally treated

patients

Sodium restriction is reasonable for patients with symptomatic HF to reduce congestive symptoms.

I IIa IIb III

Sodium Restriction

Patient with cardiomyopathy on GDMT for >3 mo or on GDMT and >40 d after MI, or with implantation of pacing or defibrillation device for special indications

LVEF <35%

Evaluate general health statusComorbidities and/or frailty

limit survival with good functional capacity to <1 y

Continue GDMT without implanted device

Acceptable noncardiac health

Evaluate NYHA clinical status

NYHA class I

• LVEF ≤30%• QRS ≥150 ms• LBBB pattern• Ischemic

cardiomyopathy• QRS ≤150 ms• Non-LBBB pattern

NYHA class II


• QRS ≤150 ms• Non-LBBB pattern


• LVEF ≤35%• QRS ≥150 ms• Non-LBBB pattern• Sinus rhythm

Colors correspond to the class of recommendations in the ACCF/AHA Table 1.

Benefit for NYHA class I and II patients has only been shown in CRT-D trials, and while patients may not experience immediate symptomatic benefit, late remodeling may be avoided along with long-term HF consequences. There are no trials that support CRT-pacing (without ICD) in NYHA class I and II patients. Thus, it is anticipated these patients would receive CRT-D unless clinical reasons or personal wishes make CRT-pacing more appropriate. In patients who are NYHA class III and ambulatory class IV, CRT-D may be chosen but clinical reasons and personal wishes may make CRT-pacing appropriate to improve symptoms and quality of life when an ICD is not expected to produce meaningful benefit in survival.

NYHA class III & Ambulatory class IV


• LVEF ≤35%• QRS 120-149 ms• Non-LBBB pattern• Sinus rhythm


• LVEF≤35%• QRS ≥150 ms• Non-LBBB pattern• Sinus rhythm

• Anticipated to require frequent ventricular pacing (>40%)

• Atrial fibrillation, if ventricular pacing is required and rate control will result in near 100% ventricular pacing with CRT

Special CRT Indications

Indications for CRT in HF

Clinical Events and Findings Useful for Identifying Patients With Advanced HF

Repeated (≥2) hospitalizations or ED visits for HF in the past year Progressive deterioration in renal function (e.g., rise in BUN and

creatinine) Weight loss without other cause (e.g., cardiac cachexia) Intolerance to ACE inhibitors due to hypotension and/or worsening renal

function Intolerance to beta blockers due to worsening HF or hypotension Frequent systolic blood pressure <90 mm Hg Persistent dyspnea with dressing or bathing requiring rest Inability to walk 1 block on the level ground due to dyspnea or fatigue Recent need to escalate diuretics to maintain volume status, often

reaching daily furosemide equivalent dose >160 mg/d and/or use of supplemental metolazone therapy

Progressive decline in serum sodium, usually to <133 mEq/L Frequent ICD shocks

1. Does the patient have a reversible cause of heart failure? 2. Is the patient on the maximum/tolerated standard medical

HF therapy? 3. Is the patient candidate for CRT-D? If yes, will it make a

difference? 4. What is the patient’s prognosis in the next year without

MCS?(High risk for mortality ≥ 50%). 5. Does the patient have any irreversible co-morbidities that

will affect quality of life and survival after MCS implantation?

6. Does the patient have adequate financial and psychosocial support, and safe living environment?

7. Does the patient have high risk behavior?

Mechanical Circulatory Support Patient selection and Evaluation

HeartMate II - BTT Outcomes

J Am Coll Cardiol 2009;54:312–21

HeartWare (HVAD) - BTT Outcomes

Circulation. 2012; 125: 3191-3200

HeartMate II - DT Outcomes

Circ Heart Fail. 2012;5:241-48

Mechanical Circulatory Support

All-cause mortality

• Change from baseline in the clinical summary score of the Kansas City Cardiomyopathy Questionnaire at 8 months

• Time to new onset of atrial fibrillation

• Time to first occurrence of a protocol-defined decline in renal function

PARADIGM-HF: Secondary Endpoints

(all comparisons are versus

enalapril 20 mg daily, not versus placebo)

0

16

32

40

24

8

Enalapril (n=4212)

360 720 1080 0 180 540 900 1260 Days After Randomization

4187 4212

3922 3883

3663 3579

3018 2922

2257 2123

1544 1488

896 853

249 236

LCZ696 Enalapril

Patients at Risk

1117

Kap

lan-

Mei

er E

stim

ate

of

Cum

ulat

ive

Rat

es (%

)

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)

Thank You!

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