Heart Failure

HFrEF

systolic heart failure, heart fails to eject blood during systole

Left ventricle ejection fraction (LVEF) <40%

HFpEF

diastolic heart failure, heart fails to fill with blood during diastole

LVEF >50%

LVEF 41%-49%

Symptoms and/or signs of HF with either elevated natriuretic peptide levels, or objective evidence of cardiogenic pulmonary or systemic congestion

fraction of blood at the end of diastole ejected from the ventricle during each contraction, normal 55-75%

Volume of blood ejected from the heart during systole, SV=end-diastolic volume - end-systolic volume

Volume of blood ejected from the ventricle per minute, CO=SV*HR

ventricular wall tension at the end of diastole, measure of how stretched the ventricular fibers are just before contraction

If preload is greater, there is more tension in the walls just before contraction, leading to an increased stroke volume. Effectively a measure of how much blood has entered the heart, therefore stretching the heart walls more.

the ventricular wall tension during contraction, the resistance that must be overcome for the ventricle to eject it's contents

As afterload increases, stroke volume decreases. Things that would increase afterload would be stuff like hypertension, vasoconstriction, there is higher blood pressure, so the ventricle has to work harder to pump it out of the heart, due to an increase in resistance that must be overcome.

Property of the heart muscle that accounts for changes in the strength of contraction, independent of pre and after load.

A measure of how hard the heart can contract, higher contractility leads to increased stroke volume. Positive inotropic drugs increase contractility, negative inotropic drugs decrease contractility.

A measure of cardiac conduction through the heart, how fast the signals are sent. Negative dromotropic drugs such as non DHP CCBs or beta blockers decrease the rate of conduction of the heart.

The left ventricle is unable to pump out enough blood, leaving leftover blood at the end of sistole and increasing the pressure in the left ventricle. This pressure backs up into the left atrium, and then back out to the pulmonary veins, increasing pulmonary pressure.

The heart can sense if the body needs more blood pumped, typically during flight or fight situations. It will increase the preload of the heart by increasing the amount of blood that fills into the heart, leading to an increased stroke volume and increased cardiac output.

In heart failure, the relationship between preload and stroke volume is significantly flattened. As the preload increases, stroke volume still fails to increase by significant amounts, leading to congestion.

It causes an increase in heart rate and contractility, which increases the cardiac output and stroke volume, thereby cardiac output, respectively. This causes the heart to pump more blood and compensate for heart failure.

It also causes vasoconstriction, which increases afterload and decreases cardiac output. It causes decreased beta adenergic receptor responsiveness in the heart, which will make the sympathetic nervous system less effective during times it needs even further heart rate increases. Additionally, the constant increased heart rate and contractility will cause cardiac hypertrophy, and eventually lead to necrosis and apoptosis. This leads to arrythmias which will further impair heart functioning. It also cause increased activity of the renin angiotensin system.

Angiotensin II production is increased, which leads to sodium retenion, increasing blood volume (increased preloading). Increase in vasoconstriction, leading to more afterload. Increased aldosterone secretion, which further retains sodium and water.

Increases both preload and afterload, by increasing vasoconstriction and blood volume

At risk for HF but without current or previous symptoms/signs of HF and without structural/functional heart disease.

Hypertension, CVD, diabetes, obesity, exposure to cardiotoxic agents, genetic variant, family history

Patients without current or previous signs/symptoms of HF, but with at least 1 of the following:
Structural heart disease
Evidence of increased filling pressures
Increased levels of natriuretic peptide or cardiac troponin without a competing diagnosis

Usually someone who had a heart attack without signs of heart failure

Patient with current or previous signs of heart failure

Marked HF symptoms that is not well controlled

Establish diagnosis of HFrEF
Address congestion
Initiate GDMT (guideline directed medical therapy)

Loop diuretics, highest level of volume reduction from any diuretic. Additionally, if there is still too much fluid retention after using loop diuretics, thiazide diuretics can be added on, as they also decrease fluid volume, just to a lesser extent, and act on a different site, so both will work together.

Furosemide (Lasix), Bumetanide (Bumex), Torsemide (Demadex)

Furosemide (Lasix)

Furosemide (Lasix), Bumetanide (Bumex), take on an empty stomach

Decreases blood volume, which decreases preload. Normally this would decrease stroke volume, however stroke volume doesn't increase much with preload in heart failure, so it doesn't have much impact on stroke volume. It does however decrease the backup of volume in the heart, which decreases pulmonary and peripheral congestion. Doesn't increase survival, but increases quality of life.

We want to titrate patients to a point where urine output increases and weight loss begins at 1-2 pounds/day. Double the dose until clinical evidence of fluid retention is relieved.

Na+, goal 135-145 mEq/L
K+, goal 4-5 mEq/L
Mg+, goal 2-3 mEq/L
Measure at baseline and every 1-2 weeks after initiation or dose increase and replace nutrients as needed

Monitor for increases in SCr/BUN and decrease dose if kidney function decreases

All 4 of the following used simultanously. An nhibitor of the renin-angiotensin system (ACEi or ARB), a beta blocker, an aldosterone antagonist, and an SGLT2i. Plus a loop diuretic if there is congestion.

Any can be used, most commonly used is lisinopril. Dosage is based off the clinical trials, we do not titrate to an end goal, we titrate to the maximum doses used in trials.

Any can be used, again, titrated up to the maximum dose used in clinical trials, not to a clinical endpoint.

neprilysin breaks down endogenous vasoactive peptides, which decrease neurohormonal activation, vascular tone, cardiac fibrosis and hypertrophy, and sodium retention. By inhibiting neprilysin, we keep these vasoactive peptides around to continue with these benefits in HF.

valsartan/sacubatril (Entresto), combines ARB and a neprilysin inhibitor, ARNI, angiotensin receptor neprilysin inhibition

Decrease sodium and water retention, leading to decreased edema and lowered preloading. Decreases potassium and magnesium excretion, which decreases arrythmias. Also decreases collagen deposition, which decreases myocardial fibrosis.

Bisoprolol (Zebeta)
Carvedilol (Coreg)
Metoprolol Succinate CR/XL (Toprol XL)

No other beta blockers are used in HF

Inhibit sodium reabsorption in the proximal tubule, leads to decreased volume, blood pressure, preloading.
Many other mechanisms of action that are not yet understood.

Dapagliflozin (farxiga)
Empagliflozin (jardiance)
Sotagliflozin (inpefa)

Vasodilatory properties
Nitrates attenuate myocardial remodeling, while hydralazine prevents nitrate tolerance
Lowers rates of hypertrophy, fibrosis, and apoptosis

In african american patients in addition to the other therapies

Funny channel (sodium channel in the SA node) blocker, which slows heart rate

CYP3A4

Soluble guanylate cyclase stimulator, which decreases inflammation and increases vasodilation in the blood vessels, and decreases inflammation, fibrosis, and hypertrophy in the heart, similar MOA to nitric oxide.

Take with food

Inhibits Na-K ATPase, therby increasing intracellular Na. This is then exchanged with the Na-Ca Exchange, which increases intracellular Ca levels, increasing contractility of the heart. Positive inotropy. Shifts the frank starling curve up, increasing stroke volume for any given preload.

Positive inotropy, negative chronotropy, slows heart rate, negative dromotropy, slows cardiac conduction

Many drug interactions with P-glycoprotein and narrow therapeutic index (0.5-0.9), difficult to manage.

Serum creatinine, which may be increased due to hypoperfusion (reduced blood flow), or preexisting renal conditions can contribute to volume overload.
CBC to determine if HF is due to reduced oxygen carrying capacity
Hyponatremia, less than 130mEq/L is associated with reduced survival, worsening fluid overload. Weight also measured in chronic HF, sudden weight gain may mean increased fluid retention.
Echocardiography, to determine estimate of ejection fraction, noninvasive
Natriuretic peptide, BNP, can support or exclude diagnosis of HF. High levels associated with HF and can be used to assess risk over time in chronic HF patients

Any patient with class II or III symptoms and HFrEF, can be started for newly diagnosed patients or switched from an ACEi. If switching from an ACEi, must wait at least 36 hours between last dose of ACEi and first dose of ARNI to reduce risk of angioedema.

First line treatment over ACEi or ARBs

History of angioedema (ACEi also carry this risk, these patients should use ARBs)
bilateral renal artery stenosis
pregnancy
poor kidney function <30mL/min
symptoms of hypotention OR SBP <90

Significant hyperkalemia >5mEq/L, RAAS inhibitor, so may cause K increase
Drug-drug interactions with other potassium increasing drugs, K+ supplements, angiotensin inhibitors (which they should be on as well), renin inhibitors (aliskiren), bactrim, NSAIDs

Check electrolyte (potassium) and kidney function
Start with lowest dose and double no sooner than every 2 weeks as tolerated up to the max dose
Recheck electrolytes and kidney function every 1-2 weeks after initiation up until the final dose titration, then every 4 months

Weeks to months for symptom relief
can cause hypotension (dizziness) and cough
Avoid NSAIDs and K+ supplements or salt substitutes high in K+ unless presribed by your doctor

Previous or current symptoms of HFrEF when entresto (ARNI) is not tolerated or feasable to use (expensive)

History of angioedema
Known bilateral renal artery stenosis
pregnancy

Significant hyperkalemia >5mEq/L
Significant kidney dysfunction <30mL/min (contraindication for ARNI)
Symptomatic hypotension or SBP <90 (contraindication for ARNI)
Drug-drug interactions with other potassium increasing drugs, K+ supplements, angiotensin inhibitors (which they should be on as well), renin inhibitors (aliskiren), bactrim, NSAIDs

Check renal function and electrolytes
start with low dose and double no more often then every 2 weeks as tolerated until reaching max dose
Check renal function and electrolytes every 1-2 weeks until final titration is done and then every 4 months
Very rarely nescessary to stop ACEi/ARB therapy, if treatment is withdrawn patient will likely experience negative side effects

Symptom improvement within weeks to months
Dizziness from hypotension and cough (no cough with ARB)
avoid NSAIDs or K+ supplements not prescribed by your doctor

Patients with current or previous HFrEF and who cannot take an ACEi due to cough or angiodema and when use of an ARNI is not feasable.

History of angioedema
Known bilateral renal artery stenosis
pregnancy

Significant hyperkalemia >5mEq/L
Significant kidney dysfunction <30mL/min (contraindication for ARNI)
Symptomatic hypotension or SBP <90 (contraindication for ARNI)
Drug-drug interactions with other potassium increasing drugs, K+ supplements, angiotensin inhibitors (which they should be on as well), renin inhibitors (aliskiren), bactrim, NSAIDs

In patients with HFrEF in NYHA class II-IV

Significant hyperkalemia >5mEq/L
Significant kidney dysfunction <30mL/min
Drug-drug interactions with other potassium increasing drugs, K+ supplements, angiotensin inhibitors (which they should be on as well), renin inhibitors (aliskiren), bactrim, NSAIDs
Eplerenone is a CPY3A4 substrate, watch for CYP3A4 inhibitors

Renal function and electrolytes
Start with low dose, can increase to high dose after 4-8 weeks (don't need to know exact timing)

Symptom improvement within weeks to months
avoid NSAIDs or K+ supplements not prescribed by your doctor
intense sweating from fever can lead to dehydration due to electrolyte imbalance, contact a doctor.

When they are healthy and have managed volume overload, not upon initial review in the hospital, will make volume overload worse due to negative inotropic effects

Severe (Class IV) HF (beta blockers are negative inotropic drugs)
Current or recent HF exacerbation
With persisting signs of congestion, hypotension
drug interactions, risk of bradycardia or AV block, verapamil/diltiazem, digoxin, amiodarone, ivabradine

Start with low dose in stable condition
double no more than every 2 weeks as tolerated up to the max dose
monitor heart rate, blood pressure, and clinical status (signs congestion or weight gain)
if worsening signs, shortness of breath, weight gain, fatigue, increase dose of loop diuretic or halve dose of beta blocker unless serious conditions

pregnancy
eGFR <20mL/min
Symptoms of hypotension or SBP <95

Risk of ketoacidosis in type 1 diabetes patients
Increased glucose in urine leads to infections
drug interactions (insulin, sulfonylurea, or other antidiabetic drugs that may cause hypoglycemia, reduce dose of other diabetes drugs in diabetic patients if needed)
may lower dose of other diuretics to prevent excessive diuresis, dehydration, ect

In *african american* patients with class III-IV HFrEF who are already receiving all other therapies (RAAS, beta blocker, MRA, SLGT2 Inhibitor, and Loop diuretic if needed), to improve symptoms and reduce mortality

In *any* patient with HFrEF who cannot be given any of the first line RAAS due to renal insufficiency or drug intolerance, may consider use in place of RAAS.

Symptomatic hypotension or SBP <90
Hydralazine may cause Lupus (watch for skin rash)
headaches and dizziness

In patients with class II or III HFrEF with a LVEF <35%, who are recieving GDMT, including a max tolerated dose beta blocker, who has a normal heart rythm but still has a heart rate of over 70 bmp at rest, in order to avoid hospitalization. (Basically anyone who's heart rate we are unable to control using beta blockers)

Unstable CV conditions (acute ACS, stroke, hypotension)
Atrial fibrilation
Severe liver dysfunction
Pregnancy or breastfeeding

Severe (class IV) HF
current or recent HF exacerbation
resting HR <50bpm during treatment
drug drug interactions, risk of bradycardia, (verapamil/diltiazem, digoxin, amiodarone)
Strong CYP3A4 inhibitors

In select high risk patients already recieving GDMT and who has a recent worsening in HF to reduce risk of hospitalization

pregnancy or breastfeeding
Avoid use with PDE-5 inhibitors (sildenafil) (they inhibit breakdown of cGMP, which vericiguat raises the levels of, high levels of vasodilation)
can cause hypotension and anemia

In patients with symptomatic HFrEF following GDMT or who are unable to follow GDMT, may be considered to reduce risk of hospitalization

ventricular fibrillation
digoxin toxicity, indicated by nausea/vomiting, visual disturbances, cardiac arrythmias, risk factors are advanced age, low body weight, impaired renal function, and electrolyte abnormalities (Low K+/Mg+) (could be an issue with loop diuretics, not likely since so many other HFrEF drugs increase K+ concentration)

0.5-0.9 ng/mL, check within 5-7 days of initiation

levels above 1ng associated with higher mortality and increased risk of toxicity

p-glycoprotein substrate, interacts with
clarithromycin/erithromycin
Amiodarone/dronedarone
itroconazole/posaconazole
cyclosporine/tacrolimus
verapamil
Quinadine/propafenone

Thiazolidinediones (pioglitazone, rosiglitazone), and the DPP-4 inhibitors saxagliptin and alogliptin

NSAIDs worsen HF symptoms and should be avoided or withdrawn

SGLT2i

Loop diuretics used for fluid retention

After that, can consider adding on MRA or ARNI, weak evidence to support ARBs, no evidence for any other drugs