Comprehensive Evaluation of the Heart Failure Patient

Stephen G. Phillips, M.D.

Assistant Professor of Medicine

Virginia Tech Carilion School of Medicine

September 25, 2015

Outline

• Causes of Heart Failure• Inpatient Evaluation at Initial Diagnosis• Medical therapy• Device therapy• Outpatient management• When to refer for advanced therapies

Definition

• Heart Failure is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricles to fill with or eject blood

Background

• Heart Failure affects approximately 6 million Americans

• Heart Failure is the most common Medicare discharge diagnosis

• Admissions rates have increased approximately 150% over the past 2 decades

• Half of the hospital admissions are patients with HFpEF

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.

www.cardiosource.com

Classification of Heart Failure

ACCF/AHA Stages of HF NYHA Functional ClassificationA At high risk for HF but without

structural heart disease or symptoms of HF.

None  

B Structural heart disease but without signs or symptoms of HF.

I No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF.

C Structural heart disease with prior or current symptoms of HF.

I No limitation of physical activity. Ordinary physical activity does not cause symptoms of HF.

II Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in symptoms of HF.

III Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms of HF.

IV Unable to carry on any physical activity without symptoms of HF, or symptoms of HF at rest.

D Refractory HF requiring specialized interventions.

Cardiosource, 2009

Case Presentation

• Mr. S is a 51 male with PMH significant for HTN ( on HCTZ 25mg daily) who presents to ED with 1 week h/o fatigue, SOB, and LE edema

• Physical Exam• Gen: NAD Vitals: BP =110/70 P=90,

afebrile,weight=185lbs pulse ox 88% RA, 92% on 2LNC

HEENT: JVP, no carotid bruits Resp: crackles 1/3 way up both lung fields

CV: RRR, normal S1S2, S3 gallop is presentABD: soft NT/ND

Skin: 2 plus pitting edema to knees bilaterally

Case Presentation-cont

• EKG: NSR, rate=90 bpm, LBBB QRS=160ms CXR: cardiomegaly, mild interstitial edema

• Labs: na=135, K=4.1, CL=100, CO2= 21, Bun=30, crt=1,2 Wbc=7000, Hgb=13.1, plt=250,000,

TSH=3.5 ,NT-proBNP= 1100pg/ml

The diagnosis of heart failure is primarily based on signs and symptoms derived from a thorough history and physical exam. Clinicians should determine the following:

a. adequacy of systemic perfusion;b. volume status;c. the contribution of precipitating factors and/or co-morbidities d. if the heart failure is new onset or an exacerbation of chronic disease; ande. whether it is associated with preserved normal or reduced ejection fraction.

Chest radiographs, echocardiogram, and echocardiography are key tests in this assessment.

The Hospitalized Patient

New

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

Diagnosis of HF

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

New

High Risk Features

Elevated BUN(>43mg/dl) or creatinine >2.75

Low SBP(<115mmhg) Hyponatremia Elevated BNP Elevated troponin Ischemic EKG changes

It is recommended that the following common potential precipitating factors for acute HF be identified as recognition of these comorbidities, is critical to guide therapy:

• acute coronary syndromes/coronary ischemia• severe hypertension• atrial and ventricular arrhythmias• infections• pulmonary emboli• renal failure• medical or dietary noncompliance

The Hospitalized Patient

New

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIIIPrecipitating Factors for Acute HF

ACC Guidelines, 2009

Cardiosource, 2011

BNP

Cardiosource, 2011

Hospitalized/Acute

Measurement of BNP or NT-proBNP is useful to support clinical judgment for the diagnosis of acutely decompensated HF, especially in the setting of uncertainty for the diagnosis.

Measurement of BNP or NT-proBNP and/or cardiac troponin is useful for establishing prognosis or disease severity in acutely decompensated HF.

I IIa IIb III

I IIa IIb III

Ambulatory/Outpatient

In ambulatory patients with dyspnea, measurement of BNP or N-terminal pro-B-type natriuretic peptide (NT-proBNP) is useful to support clinical decision making regarding the diagnosis of HF, especially in the setting of clinical uncertainty.

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

I IIa IIb III

I IIa IIb III

Ambulatory/Outpatient (cont.)

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.

Measurement of other clinically available tests such as biomarkers of myocardial injury or fibrosis may be considered for additive risk stratification in patients with chronic HF.

I IIa IIb III

I IIa IIb III

I IIa IIb III

Case Presentation-cont

• Pt received 40mg IV Lasix in the ED and transferred to telemetry unit

• UOP 1.5 L after 2 hours• BMP in AM essentially unchanged; Pt started on

40mg Lasix IV bid w/ KCL supplements• TTE performed - mildly dilated LV

( 5.3cm) - Severe global hypokinesis, EF=25%- mildly dilated LA -

- mild mitral regurgitation

Diuretics in Hospitalized Patients

Patients with HF admitted with evidence of significant fluid overload should be promptly treated with intravenous loop diuretics to reduce morbidity.

If patients are already receiving loop diuretic therapy, the initial intravenous dose should equal or exceed their chronic oral daily dose and should be given as either intermittent boluses or continuous infusion. Urine output and signs and symptoms of congestion should be serially assessed, and the diuretic dose should be adjusted accordingly to relieve symptoms, reduce volume excess, and avoid hypotension.

I IIa IIb III

I IIa IIb III

2%3%

15%

33%

24%

13%

6%7%

0

5

10

15

20

25

30

35

(<-20) (-20 to -15)(-15 to -10) (-10 to -5) (-5 to 0) (0 to 5) (5 to 10) (>10)

Change in Weight (lbs)

Pati

en

ts (

%)

Fonarow GC. Rev Cardiovasc Med. 2003;4(suppl 7): 21.

Current treatment options• Loop diuretics• IV inotropes• Nitrates• Nesiritide

More than 50% of Patients Have Little or No Weight Loss During Hospitalization

Dosing of diuretics in renal disease

Cardiosource,2011

Diuretics in Heart Failure

Acute Heart Failure (1 symptom AND 1 sign)Home diuretics dose ≥ 80 mg and ≤240 mg furosemide

<24 hours after admission

2x2 factorial randomization

High Dose (2.5x oral)Continuous infusion

48 hours

1) Change to oral2) continue current dose3) 50% increase in dose

Co-Primary endpoints: Change in creatinine from baseline to 72 hoursPGA VAS area under curve over 72 hours

Low Dose (1x oral)Continuous infusion

High Dose (2.5x oral)Q12 IV bolus

Low Dose (1 x oral)

Q12 IV bolus

72 hours

Study Design of DOSE Trial

DOSE Trial

Cardiosource, 2014

Diuretics in Hospitalized Patients (cont.)

The effect of HF treatment should be monitored with careful measurement of fluid intake and output, vital signs, body weight that is determined at the same time each day, and clinical signs and symptoms of systemic perfusion and congestion. Daily serum electrolytes, urea nitrogen, and creatinine concentrations should be measured during the use of intravenous diuretics or active titration of HF medications.

When diuresis is inadequate to relieve symptoms, it is reasonable to intensify the diuretic regimen using either:

a. higher doses of intravenous loop diuretics.b. addition of a second (e.g., thiazide) diuretic.

I IIa IIb III

I IIa IIb III

Noninvasive Cardiac Imaging

Patients with suspected or new-onset HF, or those presenting with acute decompensated HF, should undergo a chest x-ray to assess heart size and pulmonary congestion, and to detect alternative cardiac, pulmonary, and other diseases that may cause or contribute to the patients’ symptoms.

A 2-dimensional echocardiogram with Doppler should be performed during initial evaluation of patients presenting with HF to assess ventricular function, size, wall thickness, wall motion, and valve function.

Repeat measurement of EF and measurement of the severity of structural remodeling are useful to provide information in patients with HF who have had a significant change in clinical status; who have experienced or recovered from a clinical event; or who have received treatment, including GDMT, that might have had a significant effect on cardiac function; or who may be candidates for device therapy.

I IIa IIb III

I IIa IIb III

I IIa IIb III

Noninvasive Cardiac Imaging (cont.)

Noninvasive imaging to detect myocardial ischemia and viability is reasonable in patients presenting with de novo HF who have known CAD and no angina unless the patient is not eligible for revascularization of any kind.

Viability assessment is reasonable in select situations when planning revascularization in HF patients with CAD.

Radionuclide ventriculography or magnetic resonance imaging can be useful to assess LVEF and volume when echocardiography is inadequate.

I IIa IIb III

I IIa IIb III

I IIa IIb III

Noninvasive Cardiac Imaging (cont.)

Magnetic resonance imaging is reasonable when assessing myocardial infiltrative processes or scar burden.

Routine repeat measurement of LV function assessment in the absence of clinical status change or treatment interventions should not be performed.

I IIa IIb III

No Benefit

I IIa IIb III

Case Presentation

• Mr. S went for LHC on HD #2 which demonstrated mild non-obstructive CAD; LVEDP= 20.

• Pt started on carvedilol 3.125mg po bid and Lisinopril 5mg po daily

• By HD #3, IV Lasix converted to PO Lasix 40mg daily

• Pt discharged home on HD#4

Causes of Heart Failure in Western World

Most Common Causes of Heart Failure

1. Coronary Artery Disease

2. Hypertension

3. Valvular Heart Disease

4. Cardiomyopathy

Pharmacologic Treatment for Stage C HFrEF

HFrEF Stage CNYHA Class I – IV

Treatment:

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

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

NeprilysinNeprilysininhibition

LCZ696

LCZ696: Angiotensin Receptor Neprilysin Inhibition

Angiotensinreceptor blocker

Inhibition of neprilysin

2 weeks 1-2 weeks 2-4 weeks

Single-blind run-in period Double-blind period

(1:1 randomization)

Enalapril

10 mg BID

100 mgBID

200 mgBID

Enalapril 10 mg BID

LCZ696 200 mg BID

PARADIGM-HF: Study Design

Randomization

LCZ696

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

Est

imat

e o

fC

um

ula

tive

Rat

es

(%)

914

LCZ696(n=4187)

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

44

Ivabradine• Specifically binds the Funny

channel– Reduces the slope for diastolic

depolarization • Prolongs diastolic duration

• Does not alter…• Ventricular repolarization• Myocardial contractility• Blood pressure

Systolic Heart failure treatment with

the If inhibitor ivabradine Trial

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

analysis from the SHIFT study Effect of ivabradine on outcomes in patients with chronic heart failure and HR 75 bpm

www.shift-study.comBöhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22

Effect of ivabradine on primary outcomeCV death or hospitalization for HF

0 6 12 18 24 30

40

10

0

Hazard ratio=0.76

P<0.0001

Patie

nts

with

prim

ary

com

posi

te e

nd p

oint

(%)

Time (months)

20

30

Placebo

Ivabradine

www.shift-study.comBöhm M, Borer J, Ford I, et al. Clin Res Cardiol. 2013;102(1):11-22

Inpatient and Transitions of Care

The use of performance improvement systems and/or evidence-based systems of care is recommended in the hospital and early postdischarge outpatient setting to identify appropriate HF patients for GDMT, provide clinicians with useful reminders to advance GDMT, and to assess the clinical response.

I IIa IIb III

Inpatient and Transitions of Care

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; andh. consideration for palliative care or hospice care in selected patients.

I IIa IIb III

Inpatient and Transitions of Care

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

Stage C: Nonpharmacological Interventions

Patients with HF should receive specific education to facilitate HF self-care.

Exercise training (or regular physical activity) is recommended as safe and effective for patients with HF who are able to participate to improve functional status.

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

I IIa IIb III

I IIa IIb III

I IIa IIb III

Stage C: Nonpharmacological Interventions (cont.)

Continuous positive airway pressure (CPAP) can be beneficial to increase LVEF and improve functional status in patients with HF and sleep apnea.

Cardiac rehabilitation can be useful in clinically stable patients with HF to improve functional capacity, exercise duration, HRQOL, and mortality.

I IIa IIb III

I IIa IIb III

Case Presentation-cont

• Patient seen every 2 weeks for 6 weeks in HF clinic for uptitration of carvedilol and Lisinopril.

• At week 6 post-discharge, spironolactone 25mg po daily added. BMP check at 5 days and at 30 days.

• At week 16 post-discharge, patient still with NYHA class II symptoms. Repeat echo essentially unchanged with Ef=25-30%.

Device Therapy for Stage C HFrEF

ICD therapy is recommended for primary prevention of SCD to reduce total mortality in selected patients with nonischemic DCM or ischemic heart disease at least 40 days post-MI with LVEF of 35% or less, and NYHA class II or III symptoms on chronic GDMT, who have reasonable expectation of meaningful survival for more than 1 year.

CRT is indicated for patients who have LVEF of 35% or less, sinus rhythm, left bundle-branch block (LBBB) with a QRS duration of 150 ms or greater, and NYHA class II, III, or ambulatory IV symptoms on GDMT.

I IIa IIb III

I IIa IIb III

NYHA Class III/IVI IIa IIb III

NYHA Class II

Device Therapy for Stage C HFrEF (cont.)

CRT is not recommended for patients with NYHA class I or II symptoms and non-LBBB pattern with a QRS duration of less than 150 ms.

CRT is not indicated for patients whose comorbidities and/or frailty limit survival with good functional capacity to less than 1 year.

I IIa IIb III

I IIa IIb III

No Benefit

No Benefit

Indications for CRT Therapy

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 survi val.

NYHA class III & Ambulatory class IV

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

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

· LVEF ≤35%· QRS ≥150 ms· 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

Case Presentation-cont

• Pt receives CRT-D 2 weeks after repeat echo( which demonstrated EF still 25-30% range)

• Pt feels better with more energy for about 12 months after device implant

• Pt admitted in June 2015 for ADHF- treated with IV diuretics for 3

days - Cardiomems implanted HD#4

Cardiosource 2014

TeleHealth in Heart FailureWhy is it Likely to Become Essential?

1. More patients with long-term conditions– More older people– Longer survival with illness– Better primary & secondary prevention

2. More monitoring required– Higher expected standards of care– More things that can be monitored– More treatments that can be monitored

3. Patient preference and convenience

4. Reduced Cost

Telemonitoring

Non-InvasiveHome

Monitoring

Structured Telephone Support

DeviceImplant

MEMS-based pressure sensor

Cardiosource, 2014

Clinical Events and Findings Useful for Identifying Patients With Advanced HFRepeated (≥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

Adapted from Russell et al. Congest Heart Fail. 2008;14:316-21.

Cardiac Transplantation

Evaluation for cardiac transplantation is indicated for carefully selected patients with stage D HF despite GDMT, device, and surgical management.

I IIa IIb III

Mechanical Circulatory Support

MCS use is beneficial in carefully selected* patients with stage D HFrEF in whom definitive management (e.g., cardiac transplantation) or cardiac recovery is anticipated or planned.

Nondurable MCS, including the use of percutaneous and extracorporeal ventricular assist devices (VADs), is reasonable as a “bridge to recovery” or a “bridge to decision” for carefully selected* patients with HFrEF with acute, profound hemodynamic compromise.

Durable MCS is reasonable to prolong survival for carefully selected* patients with stage D HFrEF.

I IIa IIb III

I IIa IIb III

I IIa IIb III

69

Heart Mate II

A surgically implanted, rotary continuous-flow device in parallel with the native left ventricle– Left ventricle to ascending aorta

Percutaneous driveline Electrically powered

– Batteries & line power Fixed speed operating

mode Home discharge

Post-op management

• Aspirin 81mg and coumadin with INR 1.5 to 2.5

• MAP of 70-80mmhg• Acquired von-Willebrand syndrome- GI

bleeding• 10% chance of CVA per year