PhPr860B Chronic Heart Failure

Heart failure is a complex clinical syndrome resulting from any structural or functional impairment of what?

Ventricular filling or ejection of blood

What is cardiac output?

The amount of blood (in liters) the heart squeezes out per minute

What is a normal cardiac output?

4-8 L/min

What is heart rate?

Number of ventricular contraction per minute

What is a normal heart rate?

60-100 bpm

What is stroke volume?

Amount of blood ejected (mL) from the ventricle when it contracts

What is a normal stroke volume?

60-100 mL

What are the most common causes of heart failure?

-Ischemic heart disease

-Myocardial infarction

-Hypertension

-Valvular disease

What are other causes of heart failure?

-Chemo and other cardiotoxic medications

-Rheumatological or autoimmune

-Endocrine or metabolic

-Familial cardiomyopathy or inherited and genetic heart disease

-Heart rhythm related

-Infiltrative cardiac disease

-Myocarditis

-Peripartum cardiomyopathy

-Stress cardiomyopathy

-Substance abuse

What is ejection fraction?

Stroke volume / End diastolic volume

What ejection fraction is used to classify types of heart failure?

Left ventricular EF (LVEF)

What is a normal LVEF?

50-70%

What is end diastolic volume?

The amount of blood in the ventricle (mL) at the end of diastole

What is a normal end diastolic volume?

120 mL

Which heart failure has weakened heart muscles that can't squeeze as well resulting in less blood being pumped out of ventricles?

Systolic heart failure

Which heart failure has stiff heart muscle that can't relax normally resulting in less blood filling the ventricles?

Diastolic heart failure

What is the criteria for heart failure with reduced ejection fraction (HFrEF)?

LVEF 40% or less

What is the criteria for heart failure with improved ejection fraction (HFimpEF)?

Previous LVEF of 40% or less and a follow-up measurement of LVED above 40%

What is the criteria for heart failure with mildly reduced ejection fraction (HFmrEF)?

LVEF 41-49%

-Evidence of spontaneous or provokable increased LV filling pressures (ex/ elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement)

What is the criteria for heart failure with preserved ejection fraction (HFpEF)?

LVEF of 50% or more

-Evidence of spontaneous or provokable increased LV filling pressures (ex/ elevated natriuretic peptide, noninvasive and invasive hemodynamic measurement)

When blood backs up in the pulmonary vasculature and lungs, is it left or right sided ventricular failure?

Left sided

When blood backs up in the veins of the body causing peripheral edema, is it left or right sided ventricular failure?

Right sided

What can right sided ventricular failure result from?

Left sided HF, pulmonary hypertension, or pulmonary embolism

What are cardinal symptoms of heart failure?

-Dyspnea and fatigue (SOB, chronic lack of energy, difficulty sleeping due to breathing problems, swollen or tender abdomen with loss of appetite, sough with frothy sputum, confusion and/or impaired memory)

-Fluid retention (swelling of feet and legs, increased urination t night)

What are the signs of heart failure?

-Elevated jugular venous distention (JVD)

-Third heart sound (gallop rhythm) or murmur

-Weight gain (>2 kg/week)

-Pulmonary rales

-Cold extremities

Which of the following is not a sign/symptom consistent with heart failure?

Edema

SOB

Warm extremities

Orthopnea

Warm extremities

What is the ACC/AHA stage A of HF?

-At risk of HF

-Without symptoms, structural heart disease, or cardiac biomarkers of stretch or injury (ex/ pts with HTN, atherosclerotic CVD, diabetes, metabolic syndrome and obesity, exposure to cardiotoxic agents, genetic variant for cardiomyopathy, or positive family history of cardiomyopathy)

What is the ACC/AHA stage B of HF?

-Pre HF

-No signs or symptoms of HF and evidence of 1 of the following:

-Structural heart disease (reduced left or right ventricular systolic function, reduced EF, reduced strain, ventricular hypertrophy, chamber enlargement, wall motion abnormalities, valvular heart disease)

-Evidence for increased filling pressures (by invasive hemodynamic measurements, by noninvasive imaging suggesting elevated filling pressures)

-Patients with risk factors and increased levels of BNPs or persistently elevated cardiac troponin in the absence of competing diagnoses resulting in such biomarker elevations such as acute coronary syndrome, CKD, pulmonary embolus, or myopericarditis

What is the ACC/AHA stage C of HF?

-Symptomatic HF

-Structural heart disease with current or previous symptoms of HF

What is the ACC/AHA stage D in HF?

-Advanced HF

-Marked HF symptoms that interfere with daily life and with recurrent hospitalizations despite attempts to optimize GDMT

What is GDMT?

Guideline directed medical therapy

What is NYHA class I?

-No symptoms with normal physical activity

-Normal functional status

What is NYHA class II?

-Mild symptoms with normal physical activity

-Comfortable at rest

-Slight limitation of functional status

What is NYHA class class III?

-Moderate symptoms with less than normal physical activity

-Comfortable only at rest

-Marked limitation of functional status

What is NYHA class IV?

-Severe symptoms with features of heart failure with minimal physical activity even at rest

-Sever limitation of functional status

The NYHA functional class is used to characterize symptoms and functional class for patients in what stage of HF?

Stage C and D

What is NYHA functional class used to identify?

Eligibility of patients for treatment strategies

What is used in the diagnosis of HFrEF?

-Clinical evidence of HF (signs/symptoms)

-Transthoracic echocardiography (TTE) or "ECHO"

What is used in the diagnosis of HFpEF?

-Clinical evidence of HF (signs/symptoms)

-Preserved/normal LVEF of 50% or higher

-Evidence of LV diastolic dysfunction determined by ECHO or cardiac catheterization (abnormal LV relaxation/filling/distension)

What is BNP and what does it stand for?

-B-type natriuretic peptide

-Neurohormone release in response to ventricular stretch and pressure overload

What lab is used to distinguish between cardiac and pulmonary causes of edema/dyspnea?

BNP

What is the role of BNP?

-Down regulate sympathetic NS and RAAS

-Facilitate natriuresis and diuresis

-Decrease peripheral vascular resistance (PVR)

-Increase smooth muscle relaxation

What are elevated NT-proBNP per age?

-<50 yo is >450 pg/mL

-50-75 yo is >900 pg/mL

->75 yo is 1800 pg/mL

What is the treatment for stage A HF?

-Pt with HTN -> optimal control of BP

-Pt with T2DM and CVD or high risk -> SGLT2i

-Pt with CVD -> optimal management of CVD

-Pts with exposure to cardiotoxic agents -> multidisciplinary evaluation for management

-First degree relatives of pts with genetic or inherited cardiomyopathies -> genetic screening and counseling

-Pts at risk for HF -> natriuretic peptide biomarker screening

-Patients at risk for HF -> validated multivariable risk scores

What is the treatment for Stage B HF?

-Pts with LVEF 40% or less -> ACEi

-Pts with a recent MI and LVEF 40% or less -> ARB if ACEi intolerant

-Pts with LVEF 40% or less -> beta blocker

-Pts with LVEF 30% or less, >1 year survival, >40 days post MI -> ICD (implanted cardiac device)

-Pts with nonischemic cardiomyopathy -> genetic counseling and testing

What is the treatment for HFrEF stage C (step 1)?

-ARNi in NYHA II-III

-ACEi/ARB in NYHA II-IV

-Beta blocker

-MRA (aldosterone antagonist)

-SGLT2i

-Diuretics as needed

If initial treatment for HFrEF does not help and the pt has persistent HFrEF of 40% or less in stage C, what do you do (step 3/4)?

-NYHA III-IV in African American pts -> hydral-nitrates

-NYHA I-III LVEF 35% or less and >1 year survival -> ICD

-NYHA II-III, ambulatory IV, LVEF 35% or less, NSR and QRS 150 ms or more with LBBB -> CRT-D

If initial treatment for HFrEF does help stage C and has LVEF >40% with HFimpEF now, what do you do (step 2)?

Continue GDMT with serial reassessment

What are the steps of treatment for HFrEF?

-Step 1: Establish diagnosis of HFrEH, address congestion, initiate GDMT

-Step 2: Titrate to target dosing as tolerated, labs, health status, and LVEF

-Step 3: Consider these patient scenarios

-Step 4: Implement additional GDMT and device therapy as indicated

-Step 5: Reassess symptoms, labs, health status, and LVEF

-Referral for HF specialty care for additional therapy

What do you do if step 3/4 of treatment for HFrEF does not work and they have refractory HF (stage D)?

-In select patients, durable MCS

-Cardiac transplant

-Palliative care

What is captopril's target dose?

50 mg TID

What is enalapril's target dose?

10-20 mg BID

What is lisinopril's target dose?

20-40 mg QD

Do ACEIs or ARBs have lower incidence of angioedema?

ARBs

What is losartan's target dose?

5-150 mg QD

What is valsartan's target dose?

160 mg BID

What is candesartan's target dose?

32 mg QD

What is the ARNi?

sacubitril/valsartan (Entresto)

What is the target dose of Entresto?

97 mg sacubitril and 103 mg valsartan BID

What drugs negate renal angiotensin system effects like Na/H2O retention and vasoconstriction?

ACEI and ARBs

What do ACEI/ARBs prevent?

Symptoms, vasoconstriction, HTN, and cardiac remodeling

Do ACEI/ARBs reduce morbidity or mortality in HFrEF?

Yes

Side effects of ACEI/ARBs

-Hypotension

-Renal insufficiency

-Hyperkalemia

-Angioedema

-Cough

Decrease doses of ACEI/ARBs and increase monitoring if SCr is ____

>3 mg/dL or CrCl <30 mL/min

How does an ARNI work for HF?

The sacubitril component is a neprilysin enzyme inhibitor which maintains circulating BNP (inhibits breakdown) leading to vasodilation, natriuresis, and diuresis

Does the ARNI reduce morbidity and mortality in HFrEF?

Yes

What are the dosing pearls for ARNI (Entresto)?

-Do not use in combination with ACEI or ARB

-If transitioning from ACEI, stop ACEI 36 hours before

-If transitioning from ARB, stop ARB and start ARNI at time of next scheduled dose

What are the major contraindications to ARNI?

-ACEi use within 36 hours

-History of angioedema

What are the cautions with ARNI?

-eGFR <30 or child pugh B (reduce starting dose to 24/26 mg PO BID and double dose every 2-4 weeks as tolerated)

-Renal artery stenosis

-SBP <100 mmHg

What are clinical pearls with ARNI?

-May be more likely to cause symptomatic hypotension

-Not mandatory to start and AA before switching

-May have insurance coverage issues

What beta blockers do you use for HF?

-Bisoprolol

-Carvedilol

-Metoprolol succinate

Target dose for bisoprolol

10 mg QD

Target dose for carvedilol

25-50 mg BID

Target dose for metoprolol succinate

200 mg QD

Rationale behind using beta blockers for HF

They prevent activation of the sympathetic NS improving LV systolic function. They decrease HR, contractility and rate of AV conduction which decreases BP and myocardial O2 demand

Do beta blockers reduce morbidity and mortality in HFrEF?

Yes

Side effects of beta blockers

-Bradycardia

-Fatigue

-Reduced exercise tolerance

-Bronchospasm

-Depression

-Hypotension

What are contraindications for beta blockers?

-Severe bradycardia

-Sick sinus syndrome

-2nd or 3rd degree AV block

-Severe bronchial disease

What are the aldosterone antagonists (aka mineralocorticoid receptor antagonists)?

-Spironolactone

-Eplerenone

Target dose of spironolactone

20-50 mg QD

Target dose of eplerenone

50 mg QD

Rationale for AA use in HFrEF?

Blocks aldosterone release by RAAS activation which decreases sympathetic activation, parasympathetic inhibition, and cardiac remodeling

Do aldosterone antagonists reduce morbidity and mortality in HFrEF?

Yes

Side effects of aldosterone antagonists?

-Hyperkalemia

-Gynecomastia

-Sexual dysfunction

-Drowsiness

What aldosterone antagonist has less gynecomastia risk?

Eplerenone

Contraindications to aldosterone antagonists

-Potassium 5 or higher

-SCr of 2.5 or higher in men, 2 or higher in women

-Hx of hyperkalemia

-Worsening renal failure

What are the SGLT2 inhibitors used in HF?

-Dapagliflozin

-Empagliflozin

Target dose of dapagliflozin

10 mg QD

Target dose of empagliflozin

10 mg QD

Rationale for SGLT2 inhibitors in HF

Unclear, but likely related to osmotic diuresis and natriuresis, decrease in arterial pressure and stiffness, shift to ketone-based myocardial metabolism

Do SGLT2i's reduce morbidity and mortality in HFrEF? With or without DM?

Yes, both with or without

Indications for SGLT2 inhibitors in HF

-HFrEF (LVEF 40% or less) with or without DM

-NYHA class II-IV HF

-Adminstered in conjunction with a background of GDMT for HF

Contraindications for SGLT2 inhibitors

-Not approved for use in patients with type 1 diabetes due to increased risk of DKA

-Known hypersensitivity

-Lactation

-On dialysis

Cautions for SGLT2 inhibitors

-eGFR less than 30 for dapagliflozin and less than 20 for empagliflozin

-Pregnancy

-Increased risk of mycotic genital infections

-May contribute to volume depletion (diuretic dose adjustment may be warranted)

-DKA- assess pt for s/s regardless of blood glucose levels

-AKI - consider temporary discontinuation

-May cause urosepsis/pyelonephritis

-May cause necrotizing fasciitis of the perineum (Fournier's gangrene) in both male and female patients

What is the If channel inhibitor for HF?

Ivabradine

Ivabradine target dose

7.5 mg BID

Rationale for If channel inhibitor in HF

Selectively inhibits If current in sinus node to reduce heart rate with little effect on BP and reduces HF hospitalization

Does the If channel inhibitor decrease morbidity and mortality in HFrEF?

No, just hospitalizations

Indications for If channel inhibitor

-HFrEF (LVEF 35% or less)

-NYHA class II-III HF

-On max tolerated dose of beta blocker

-Sinus rhythm with a resting heart rate of 70 beats/min or more

Contraindications for If channel inhibitors

-HFpEF

-HR below 60 bpm

-Atrial fibrillation or atrial flutter

(-Atrial pacemaker dependence

-Presence of angina with normal EF

-Child-Pugh C

-BP <90/50 mmHg

-Sick sinus syndrome with no pacemaker

-SA nodal block , 2nd or 3rd degree block without a pacemaker)