HFpEF, HFmrEF, and Drug Induced HF Treatments

What causes HFpEF

the most common cause is long standing hypertension leading to myocyte hypertrophy in the LV, can also be caused by CAD

Top treatments for HFpEF

diuretics as needed and SGLT2i

What is important to control in HFpEF patients

control hypertension and atrial fibrillation in accordance with guidelines

Why are SGLT2i good for HFpEF patients

they can decrease HF hospitalizations and CV mortality

Which med classes only decrease hospitalizations in HFpEF patients?

MRAs, ARBs, ARNis

agents used for fluid management in HFpEF patients?

primary agents used are loop diuretics

primary goal of fluid management treatments in HFpEF

primary goal is NaCl and water excretion

What is the biggest concern of using diuretics in HFpEF patients?

removal of too much volume (over diuresis)

why is hypovolemia a concern for HFpEF patients on diuretics

these patients already have trouble filling enough blood to pump adequately so removal of an excess amount of fluid can lead to even less profusion

top med classes for HFmrEF treatment

diuretics as needed and SGLT2 inhibitors

Patients with current or previous HFmrEF may also be given what classes of meds to reduce HF hospitalizations and CV mortality, especially if EF is on the low end of the spectrum

beta-blockers, ARNI/ACEi/ARB, and MRAs

how can HFmrEF patients benefit from SGLT2 inhibitors

they decrease HF hospitalizations and CV mortality

Do you keep home GDMT when patients are experiencing acute decompensated HF

Keep on if at all possible

Which meds would you not want to discontinue in a ADHF patient?

beta-blockers, ARNI/ACEi/ARB to prevent rebound adrenergic output/vasoconstriction (further worsening HF)

What can be done if ADHF patients cannot stop taking their beta-blocker/ARNI/ACEi/ARB?

if required the dose can be decreased instead of discontinued

If ADHF patient is hemodynamically unstable and is requiring a vasopressor, should any meds be stopped?

Yes stop taking beta-blockers, ARNI/ACEi/ARB

If an ADHF patient has AKI which meds need to be stopped?

Hold ARNI/ACEi/ARB, MRA

Should ADHF patients be continued on their SGLT inhibitors?

Keep on if at all possible as these may actually help improve diuresis

Do you need to worry about worsening renal function in ADHF patients on SGLT inhibitors?

No!!

In which scenario would an ADHF patient stop SGLT inhibitors?

if euglycemic ketoacidosis or pending procedure/surgery

Class I?

Warm and Dry (perfusing and no signs of congestion)

Which ADHF classification is ideal for patients?

Class I!!!!

What does class II ADHF mean?

warm and wet (perfusing and signs of congestion)

If an ADHF patient is Class II which class do we want to bring them down to if possible?

Class I : warm and dry

If an ADHF patient is class II what should be done?

Nothing needs to be done to ‘warm’ them up because they are perfusing, but they need to be ‘dried’ out to decrease the symptoms of congestion

How to treat ADHF patients who have congestion symptoms?

Give a 1.5-2.5 x home dose of their diuretic IV

If an ADHF patient is not on a home diuretic what diuretic should be given to them?

furosemide 40 mg IV or equivalent

What is the goal urine output response over the first 6 hours of giving an ADHF class II patient a diuretic?

500 mL over 6 hours

If an ADHF Class II patient has a poor response to the given diuretic (<500mL of pee over 6 hours), what can be done?

Double the dose given!!

Goal urine output for ADHF class II patients for the day?

1-2 liter NEGATIVE/day

What is an ADHF class III patient?

cold and dry (no perfusion ☹ but no congestion symptoms!)

What class do we want to move ADHF class III patients to if possible?

Class I (:

If an ADHF patient is class III what should be done?

nothing needs to be done to ‘dry’ them out, but they need to be ‘warmed’ up (increase perfusion)!

How do we warm up class III ADHF patients?

Via vasodilation and increased inotropy

Why are vasodilators a good option to increase perfusion in ADHF patients?

arterial vasodilation makes it easier to move blood forward from the LV (decreases afterload)

Which ADHF patients are vasodilator best for?

those who are hemodynamically stable and need to be ‘warmed’ up

Vasodilator agents that can be used in ADHF patients

ARNI/ACEi/ARB, hydralazine, IV vasodilators

Why are drugs that increase inotropy a good option for ADHF patients who need to be ‘warmed’ up?

the increased squeeze of the LV helps to move blood forward

Which ADHF patients are the best to receive inotropic agents?

they are best in patients with low blood pressure but are NOT in shock

Inotropic agents:

Dobutamine and milrinone

What class is nitroglycerin?

vasodilator

what class is nitroprusside?

vasodilator

nitroglycerin contraindications in HF?

Concurrent use with PDE-5 inhibitors and concurrent use with soluble guanylate cyclase stimulators (vericiguat, riociguat)

Monitoring for ADHF patients using nitroglycerin

BP and HR

ADRs of nitroglycerin

HA and hypotension

How is nitroglycerin given to ADHF patients?

continuous infusion

Monitoring for ADHF patients using nitroprusside

bp, and cyanide/thiocyanate toxicity (particularly if on for > 3 days at > 3 mcg/kg/min)

ADRs for nitroprusside

hypotension, and cyanide/thiocyanate toxicity (by arterial blood gas or levels)

How is nitroprusside given to ADHF patients?

continuous IV infusion

What broad class is dobutamine

Inotrope

MOA for dobutamine

stimulates myocardial beta1-adrenergic receptors resulting in increased contractility and HR. Stimulates both beta-2 and alph-1 receptors in the vasculature. The effects of beta-2 receptor activation may equally offset or be slightly greater than the effects of alpha1 stimulation, resulting in some vasodilation in addition to the inotropic and chronotropic actions.

DDI with dobutamine

increases arrhythmogenic potential in combo with other pro-arrythmic agents

monitoring for dobutamine

BP, HR, ECG for arrythmias

ADRs for dobutamine

increased or decreased bp, increased HR, arrhythmias

Pearls of dobutamine

high risk of arrhythmia, moderate-low risk of hypotension - given as a continuous IV infusion

Broad class of milrinone?

Inotrope

MOA of milrinone

a selective phosphodiesterase-3 inhibitor in cardiac and vascular tissue, resulting in vasodilation and inotropic effects

DDI with milrinone

Anagrelide: category X; increased arrhythmogenic potential in combo with other pro-arrhythmic agents

Monitoring for milrinone

BP, HR, and ECG for arrythmia

ADRs for milrinone

increased or decreased BP, increased HR, and arrhythmia

Pearls for milrinone

moderate risk of arrhythmia, high risk of hypotension; is renally eliminated (more renal dysfunction = more drug exposure and hypotension); Given as a continuous IV infusion

What is class IV ADHF

cold and wet (no perfusion and signs of congestion)

Which category do we want to bring class IV ADHF patients to if possible?

Class II (warm and wet) and eventually get them to Class I (warm and dry)

How to warm up Class IV ADHF patients?

vasodilation, inotropy, and vasopressors

Why can vasopressors help class IV patients warm up?

provides increased squeeze of the LV and vasoconstriction to keep BP high

When should vasopressors be used in ADHF patients that need to be warmed up?

If the patient is hemodynamically unstable

How do we dry class IV ADHF patients?

once they are warm utilize loop diuretics

Why must class IV be warmed up before they can be dried up?

They need to have cardiac output to deliver blood and then drug to the kidneys

Vasopressor agents:

Norepinephrine, epinephrine, and dopaine

MOA for NE/E/Dopamine

generally alpha/beta agonists to increase inotropy/chronotropy and vasoconstriction

DDI for vasopressors

increase arrhythmogenic potential in combo with other pro-arrhythmic agents

Monitoring for vasopressors

BP, HR, and ECG for arrhythmias

ADRs for vasopressors

increase BP, increased HR, arrhythmia, extravasation

Pearls for vasopressors

Norepinephrine is the first-line agent for cardiogenic shock (the best!!). Dopamine increases fatal arrhythmia and mortality in cardiogenic shock (AVOID). Given as a continuous IV infusion

Three main causes of induced HF

sodium and volume retention, direct cardiotoxicity leading to cardiomyopathy, and negative inotropy

T/F: some drugs can contribute to more than one mechanism of causing HF?

True rip

Drugs that lead to HF due to sodium and fluid retention

NSAIDs, steroids, thiazolidinediones

drugs that lead to HF due to cardiomyopathy

chemotherapeutic agents, biologics, alcohol

drugs that lead to HF due to negative inotropy

Non-DHP CCBs, beta-blockers

which drugs should be avoided if possible patients with HF, but if necessary, will need either a dose decrease or decreased duration of use

NSAIDs and steroids

which drugs increases sodium and water retention along with increased systemic vascular resistance?

NSAIDs

which drugs have a BBW to avoid use in patients with NYHA III-IV HF?

TZDs!!!!

Which chemotherapy agents can cause HF due to cardiomyopathy?

anthracyclines, alkylating agents, and many more - new agents?

which biologic agents can cause HF due to cardiomyopathy

trastuzumab and many more - new agents?

What has a direct toxic effect on the myocardium which is why it can lead to HF from cardiomyopathy?

Alcohol

Most common anthracyclines?

doxorubicin and daunorubicin

MOA of anthracyclines

inhibits topoisomerase II which causes DNA damage and induction of apoptosis - leads to increased free radicals of oxygen and defective mitochondrial biogenesis

what is the mediator for anthracycline induced cardiomyopathy

Topoisomerase 2B (TOP2B)

Where is TOP2B located in the body

in all cells including cardiac myocytes

Which drug can bind to TOP2B to prevent anthracycline binding?

Dexrazoxane

Treatment related risk factors for toxicity from anthracyclines

cumulative dose of anthracycline (> 400 mg/m2), dosing schedules, previous anthracycline therapy, radiation therapy, co-administration of potentially cardiotoxic agents

Patient related risk factors for toxicity from anthracycline

age, preexisting cardiovascular disease or risk factors, obesity, smoking, gender?

What is the lifetime dose limit for anthracycline use?

550 mg/m2

What is trastuzumab?

A HER2 receptor antagonist that can be used in certain types of breast cancer

Is cardiomyopathy reversible when caused by trastuzumab?

Yes, it is usually reversible once the drug is discontinued

Risk factors for development of cardiomyopathy from trastuzumab?

advanced age, presence of CV comorbidities, previous treatment with anthracyclines

Inhibition of HER2 receptors leads to HF due to what?

Increased reactive oxygen species (ROS), reduced NOS expression, reduced NO bioavailability, increased angiotensin II

Which drug has no contraindications based on manufacturer, but it is recommended to avoid in patients with a history of HF

Trustuzumab (evaluate LVEF in all patients prior to and during treatment)

BBW for trastuzumab

Associated with symptomatic and asymptomatic reductions in left ventricular ejection fraction (LVEF) and development of HF

Treatment for trastuzumab induced cardiomyopathy

dose adjustments based on LVEF, consider dose reduction or discontinuation if HF develops, consider using HF medications during treatment if EF declines (such as: ACEi/ARBs, Beta-blockers)