Cardiology Exam 3

Women have a _____ mortality rate due to heart failure than men

Higher

Heart failure

The heart’s inability, particularly the ventricles, to pump enough blood to meet the body’s metabolic demands

Heart failure can be caused by any disorder that affects the heart’s ability to _____

Receive or eject blood

While naturally the heart becomes weaker as we age, multiple pathologies can accelerate the process including:

Atherosclerosis

Diabetes

Mitral stenosis

Chronic hypertension

Dyslipidemia

Thyroid disorders

Myocardial infarction

Left heart failure (LHF)

Decreased ability of the left ventricle to either contract (systolic) or fill (diastolic)

Occurs when the left ventricle cannot pump blood efficiently enough to supply the body’s metabolic demand

Right heart failure (RHF)

Decreased ability of the right ventricle to either contract (systolic) or fill (diastolic)

Commonly caused by an inability of the right ventricle to efficiently pump blood whether by contraction or volume

High output heart failure

Characterized by increased cardiac output, but low systemic vascular resistance (dilations of blood vessels)

Left heart failure can lead to _____

A buildup of fluid in the lungs and other devastating complications

Compensatory effects for decreased cardiac output lead to changes in size, shape, and structure of myocytes, called cardiac remodeling

Systolic LHF

Caused by decreased contractility of the left ventricle

Left ventricle becomes dilated, or enlarged, causing increased volume of blood contained within

Systolic LHF is primarily caused by damage to the myocardium from:

MI

Dilated cardiomyopathy

Myocarditis (less common)

Decreased contractility from systolic LHF leads to _____

Decreased left ventricular ejection fraction (LVEF) called heart failure with reduced ejection fraction (HFrEF)

• Typically <40%

Diastolic LHF

Caused by decreased ability of the left ventricle to fill appropriately

An inability to overcome the pressure needed to push blood throughout (afterload)

Diastolic LHF is commonly caused by conditions that impart systemic vascular resistance such as:

Hypertension

Aortic stenosis

Hypertrophic cardiomyopathy

In patients with diastolic LHF, the LVEF is _____

Normal or preserved

• Termed heart failure with preserved ejection fraction (HFpEF)

• Typically >50%

Pulmonary congestion

Decreased ability of the heart to eject blood caused a buildup in tune heart that can translate backwards leading to pulmonary congestion and increased pulmonary capillary wedge pressure (PCWP)

Potential complications of pulmonary congestion

End result of this fluid buildup in the lungs is pulmonary edema making it hard to breathe, particularly when exercising or laying down

Can lead to hypoxia if pulmonary edema becomes severe

Cardiogenic shock

Decreased CO caused by LHF causes decreased systemic perfusion, leading to organ malperfusion

Extremities may present as cold and pale, with mottling (marbled patches of purple, red, blue discoloration indicating ineffective oxygen supply)

Cardiogenic shock can lead to:

Encephalopathy

TIA/CVA

Myocardial infarction

Acute kidney injury

Acute mesenteric ischemia

Buildup of lactate (lactic acidosis)

Systolic RHF

Caused by decreased contractility of the right ventricle

• Really only caused by MI of the right ventricle myocardium, but plausible damage to the myocardium for any reason can also be the etiology of RHF

Decreased contractility in systolic RHF leads to _____

Decreased right ventricular ejection fraction (RVEF)

Diastolic RHF

Caused by decreased ability of the right ventricle to fill appropriately

An inability to overcome the pressure needed to push blood (pulmonary afterload) into the lungs causes hypertrophy of the right ventricle, narrowing the volume within

RVEF in these patients is normal or preserved

Diastolic RHF is commonly caused by conditions that impart an increase in pulmonary vascular resistance such as:

Pulmonary hypertension

Pulmonary embolism

Lung disease (COPD, emphysema, etc.)

LHF (most common)

What is the main, most detrimental complication of right heart failure?

Increased central venous pressure (CVP)

• Presents in two ways:

  • Pitting edema

  • Jugular vein distention

Central venous pressure (CVP)

Pressure experienced in the large veins (superior and inferior vena cava) and right atrium

Complications of right heart failure

Increased central venous pressure

As blood is continually backed up particularly from the liver, emptying into the inferior vena cava, the liver can become congested and lead to liver failure

Portal vein hypertension can lead to capillary leak of the mesenteric vessels resulting in fluid buildup in the peritoneum, or ascites

Extreme dilation of the right ventricle can cause a septal shift where the right ventricle becomes so enlarged it collapses the volumetric space of the left ventricle

• Uncommon

High output heart failure (HOHF) is caused by _____

Extreme vasodilation of the systemic vasculature

Vasodilation in HOHF leads to _____

Drop in the total peripheral resistance → lowers blood pressure → body compensates by activating the SNS in an effort to raised blood pressure → in the heart, this raises heart rate and stroke volume

• This increases cardiac output, but is insufficient to overcome the minimal TPR, and will be in a constant downward spiral of the body trying to increase its cardiac output

Mechanism of hydralazine for CHF

Direct arteriolar vasodilation

• Acts primarily on arterioles NOT veins

Hemodynamic effects

How does hydralazine cause direct arteriolar vasodilation?

Exact MOA is not fully defined

Can open vascular smooth muscle K⁺ channels, ultimately leading to a decreased concentratration of intracellular Ca²⁺ → desired arterolar smooth muscle relaxation and arteriolar vasodilation

How does hydralazine cause hemodynamic effects in CHF?

Decreases afterload → systemic vascular resistance falls

Allows the failing left ventricle of the heart to eject blood more effectively, which improves the stroke volume and cardiac output of the heart

Additionally, an increase in renal perfusion can also enhance diuresis and reduce fluid overload in CHF

Afterload

The force (arterial pressure) the heart must pump against to push blood out to the rest of the systemic circulation

When used alone for CHF, hydralazine can cause _____

Reflex sympathetic activation (tachycardia, stimulation of RAAS), which may worsen CHF

Preload

The strech of heart muscle that is caused by the amount of blood filling the ventricles before the heart contracts

Mechanism of isosorbide dinitrate in CHF

Primarily dilates veins (venodilation)

Prodrug of nitric oxide

Nitric oxide stimulates guanylyl cyclase → increases conversion of GTP to cGMP, an active vasodilator → vascular smooth muscle relaxation

The main differences in action of hydralazine and isosorbide dinitrate are that hydralazine targets _____ and lowers _____, while ISDN targets _____ and decreases _____

Arterioles; Afterload; Veins; Preload

Hemodynamic effects of isosorbide dinitrate in CHF

Predominantly causes venodilation

Decreases preload

Lower preload reduces wall stress and pulmonary congestion, thus improving CHF symptoms of dyspnea and edema

At higher doses, can cause some arterial vasodilation, which contributes modestly to decreasing afterload

• Minor

Benefits of combining hydralazine and isosorbide mononitrate into BiDil

Enhances adherence, simplifies the regimen, decreases pill burden, and improves patient compliance, all of which are important in CHF where polypharmacy is common

Hydralazine and isosorbide dinitrate work together to _____

Improved cardiac output without direct inotropy (increase in force or strength of heart contraction)

Main limitation of hydralazine

Drug-Induced Lupus Erythematosus (DILE) in “slow acetylators”

In some people, hydralazine is not broken down quickly, so it can build up and trigger the immune system to make antibodies that attack the body’s own tissues

Main limitation of isosorbide dinitrate

The development of drug tolerance (Increased dose needed to produce a given effect)

• Can limit the long-term effectiveness if dosing intervals don’t allow for a “nitrate-free” period

BiDil is often described as the first _____

“Race-based” prescription drug

• Approved as adjunct therapy for self-identified

What drug class is contraindicated with isosorbide dinitrate?

PDE-5 inhibitors

• PDE-5 converts cGMP to GMP, which is inactive

• Inhibition of PDE-5 increases levels of cGMP → severe hypotension

Mechanism of SGLT2 inhibitors

Inhibit Sodium-Glucose co-Transporter 2 (SGLT2) in the renal proximal tubule of the kidney

• SGLT2 is primarily responsible for reabsorbing the majority (~90%) of filtered glucose from the urine back into the blood

  • Originially used for diabetes

The benefits of SGLT2 inhibitors in CHF are likely related to _____

Diuresis and natriuresis

Decreased preload and/or afterload

Recommended uses for SGLT2 inhibitors for heart failure

FDA-approved for patients with HFrEF without diabetes after demonstrating a decrease in mortality and hospitalizations

• Added benefit in patients with type 2 diabetes

Recommended for chronic heart failure as add-on therapy to Entresto, a beta blocker, or a MCR antagonist

The dosing of SGLT2 inhibitors is based on _____

How well a patient’s kidneys are working, via their eGFR (estimated glomerular filtration rate)

Side effects of SGLT2 inhibitors

Hypotension

Hypoglycemia

Increased urination

Weight loss

Increased thirst

A notable warning associated with SGLT2 inhibitors

Can cause severe genital fungal infections and UTIs

• Bacteria and fungi are using the excess glucose in the urine as a food source

Mechanism of ivabradine

Selective sinoatrial node inhibitor

Specifically binds to HCN4 proteins that are highly expressed on the sinoatrial (SA) node of the heart → blocking HCN4 reduces cardiac pacemaker activity, selectively slowing heart rate and allowing more time for blood to flow to the myocardium

Acts on the funny current (I_f), one of the most important ionic currents for regulating pacemaker activity in the SA node → inhibition of I_f channel reduces heart rate and workload on the heart

Ivabradine has proven efficacious for treating HFrEF due to its unique ability to _____

Selectively decrease heart rate without affecting blood pressure or heart contractility

• Allows more time for ventricle filling and improved cardiac efficiency

• Unlike other common heart rate reducing medications that are negative chronotropes and negative inotropes

Ivabradine reduces the risk of hospitalizations of worsening heart failure, but it does NOT affect _____

Mortality

To use ivabradine, patients must:

Already be on mortality-reducing medications, including target or maximally-tolerated doses of a beta blocker

Be in sinus rhythm (normal SA node driven rhythm)

Have a resting heartrate of ≥70 bpm

Warnings for ivabradine

Bradycardia

Increased risk of QT interval prolongation

Increased risk of ventricular arrhythmias

Increased risk of atrial fibrillation

Digoxin is chemically classified as a _____

Cardiac glycoside

Mechanism of digoxin

Binds to and inhibits Na⁺/K⁺ ATPase in the myocardium (heart muscle cells) → increased the concentration of calcium in heart muscle cells → strengthens the force of contraction of the heartbeat

Primary physiological results of digoxin

Increases cardiac output by creating a positive inotropic effect (Increases force of contraction)

Exerts a parasympathetic effect, which causes a negative chronotropic effect (Decreases heart rate)

Digoxin does NOT improve patient survival, but it can reduce _____

Heart failure related hospitalizations

General uses of digoxin in heart failure

Can be added to mortality-reducing drugs to improve symptoms of heart failure, exercise tolerance, and quality of life

Added for atrial fibrillation in those with HFrEF and low blood pressure

The therapeutic range of digoxin for heart failure is _____

0.5-0.9 ng/mL

• Very narrow therapeutic range → easy to overdose

Patient counseling points for digoxin

Stay hydrated

• Otherwise an overdose could occur more easily via decreased blood volume

Symptoms of an overdose include nausea, vomiting, decreased appetite, confusion, and delirium

• Somewhat classic sign of digoxin toxicity → blurred/double vision with greenish-yellow halos around lights or objects, as well as altered color perception

Many drug interactions with other drugs that decrease heart rate

Antidote for digoxin toxicity

DigiFab

• Digoxin-specific antibody that can neutralize excess digoxin

A diagnosis of heart failure means a patient has _____

Cardiomyopathy + symptoms

Etiology/Causes of heart failure

Ischemic cardiomyopathy

• Coronary artery disease

  • Myocardial ischemia and infarction

Non-ischemic cardiomyopathy

• Dilated cardiomyopathy

  • Valvular heart disease, arrhythmias, alcoholism, cardiotoxic drugs, thyroid disease, diabetes, sepsis, myocarditis, pericarditis, peripartum, stress, familial, idiopathic

• Hypertrophic cardiomyopathy

  • Hypertension, familial, idiopathic

• Restrictive cardiomyopathy

  • Amyloidosis, sarcoidosis, chemotherapy, and/or radiation exposure, idiopathic

Other

• Pulmonary

  • Pulmonary embolism, pulmonary hypertension, COPD/asthma, sleep apnea

Medications that can cause/worsen HF

Antiarrhythmics (Class I agents, dronedarone, sotalol)

Chemotherapy (anthracyclines (Ex. doxorubicin), trastuzumab, cyclophosphamide)

Non-DHP calcium channel blockers (diltiazem, verapamil)

Thiazolidinediones (rosiglitazone, pioglitazone)

Dipeptidyl peptidase-4 inhibitors (saxagliptin, sitagliptin)

Cilostazol

Corticosteroids

NSAIDs (aspirin can be used for cardioprotection)

Normal ejection fraction

50-70%

Ejection fraction in HFpEF

≥ 50%

Ejection fraction in HFmrEF

41-49%

Ejection fraction in HFrEF

≤ 40%

Most common cause of HFpEF

Hypertension

Symptoms of right heart failure

Congestion of peripheral tissues

• Dependent edema and ascites

• GI tract congestion

  • Anorexia, GI distress, weight loss

• Liver congestion

  • Signs related to impaired liver function

Symptoms of left heart failure

Decreased cardiac output

• Activity intolerance and signs of decreased tissue perfusion

Pulmonary congestion

• Impaired gas exchange

  • Cyanosis and signs of hypoxia

• Pulmonary edema

  • Cough with frothy sputum

  • Orthopnea

  • Paroxysmal nocturnal dyspnea

NYHA Class I HF

No limitation of physical activity

Ordinary physical activity does not cause HF symptoms

NYHA Class II HF

Slight limitation of physical activity

Comfortable at rest, but ordinary physical activity results in HF symptoms

NYHA Class III HF

Marked limitation of physical activity

Comfortable at rest, but less than ordinary activity causes HF symptoms

NYHA Class IV HF

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

What is the main difference between NYHA HF Classes and HF Stages A-D?

Patients can move up or down the NYHA classes, but can only get progressively worse in terms of Stages A-D

Nonpharmacological therapy of HF

Restrict sodium intake to < 1500 mg/day

Restrict fluid intake to 1.5-2 L/day if signs of congestion

Monitor and document body weight daily

Eat a heart-healthy diet

Improve functional status with exercise or cardiac rehabilitation

Quit smoking

Limit alcohol intake

Continuous positive airway pressure in patients with HF and sleep apnea

Four pillars of HFrEF pharmacotherapy with mortality benefit

ARNI

• If pt can’t use → ACEI or ARB

Beta blocker

MRA

SGLT2I

General dosing principle for treating HF

Start low and titrate to target or maximally tolerated dose

• Target dose is what has shown mortality benefits

• Continue to increase to target even if patient feels better + don’t stop meds

Recommendation for ACEIs in HFrEF

Use in patients to reduce morbidity and mortality when the use of an ARNI is not feasible

Recommendation for ARBs in HFrEF

Use in patients to reduce morbidity and mortality when the use of an ARNI is not feasible and patient is intolerant to ACEIs because of cough or angioedema

ARBs recommended in HFrEF

Candesartan

Losartan

Valsartan

Recommendation for ARNIs in HFrEF

Use to reduce morbidity and mortality in place of an ACEI or ARB (unless contraindications, intolerance, or inaccessibility exist)

Adverse Effects of ARNIs

Dry, hacking cough

Angioedema

Hyperkalemia

Hypotension

Renal dysfunction

Dizziness

Contraindications for ARNIs

Use within 36 hours of an ACEI

History of angioedema associated with ACEI or ARB therapy

Use with aliskiren in patients with diabetes

Pregnancy (teratogenic)Mo

Monitoring for ARNUs

Blood pressure

Potassium

Renal function

Drug Interactions with ARNIs

ACEI, ARB, aliskiren

BNP is not an accurate marker of _____ if on Entresto

Fluid status

• Monitor NT-proBNP instead

Recommendation for beta blockers in HFrEF

Use 1 of the 3 with proven mortality benefits in stable, euvolemic patients

• Euvolemic → normal fluid status (decongested)

Beta blockers recommended in HFrEF

Bisoprolol

Carvedilol

Metoprolol succinate

Recommendation for MRAs in HFrEF

Use to reduce morbidity and mortality in patients with serum potassium < 5 mEq/L and eGFR > 30 mL/min/1.73 m²

Recommendation for SGLT2 inhibitors in HFrEF

Use to reduce morbidity and mortality, irrespective of the presence of type 2 diabetes

SGLT2 inhibitors recommended in HFrEF

Dapagliflozin

Empagliflozin

Adverse Effects of SGLT2 Inhibitors

Dehydration

Urinary tract infection

Genital mycotic infection

Renal dysfunction

Hypoglycemia if used in combination with insulin or a sulfonylurea

• Very rare in monotherapy

Contraindications for SGLT2 Inhibitors

Known hypersensitivity to drug

Patients on dialysis

Monitoring for SGLT2 Inhibitors

Blood pressure

Volume status

Renal function

Glucose

Drug Interactions with SGLT2 Inhibitors

Caution with diuretics

• May need to lower diuretic dose or discontinue diuretic

eGFR requirements for SGLT2 inhibitor therapy

eGFR ≥ 25 for dapagliflozin and ≥ 20 for empagliflozin before initiation

• If eGFR is lower, drug will not be able to reach its site of action due to not enough renal perfusion

Recommendation for hydralazine/isosorbide dinitrate in HFrEF

Use to reduce morbidity and mortality in African American patients who are receiving optimal medical therapy

Can be useful in patients who cannot be given an ARNI, ACEI, or ARB because of drug intolerance or kidney dysfunction

Adverse Effects of Hydralazine/Isosorbide Dinitrate

• Headache

• Hypotension

Hydralazine

• Peripheral edema

• Reflex tachycardia

• Palpitations

• Drug-induced lupus

ISDN

• Dizziness

• Syncope