Therapy of Chronic Heart Disease Flashcards
Heart failure (HF) is a progressive clinical syndrome associated with:
Impairment of the ability of the ventricle to fill with or eject blood
HF may be caused by an abnormality in:
1) Systolic function
2) Diastolic function
3) Both
What are the leading causes of HF?
1) Coronary artery disease
2) Hypertension
In heart failure with reduced ejection fraction (HFrEF) there is a decrease in:
Cardiac output
What compensatory responses happen due to heart failure with reduced ejection fraction (HFrEF)?
1) Activation of the sympathetic nervous system (SNS) and the renin–angiotensin–aldosterone system (RAAS)
2) Vasoconstriction
3) Sodium and water retention
4) Ventricular hypertrophy and remodeling
Pharmacotherapy targeted at ____ has slowed the progression of HFrEF and improved survival.
Antagonizing the neurohormonal activation
Heart failure with preserved ejection fraction (HFpEF) is primarily due to:
1) Diastolic dysfunction
2) Disturbances in relaxation
What are the causes of systolic dysfunction (decreased contractility)?
1) Reduction in muscle mass (MI)
2) Dilated cardiomyopathies
3) Ventricular hypertrophy
4) Pressure overload (systemic or pulmonary hypertension, aortic or pulmonary valve stenosis)
5) Volume overload (valvular regurgitation, shunts, high-output states)
What are the causes of diastolic dysfunction (restriction in ventricular filling)?
1) Increased ventricular stiffness
2) Ventricular hypertrophy (hypertrophic cardiomyopathy, others)
3) Infiltrative myocardial diseases (amyloidosis, sarcoidosis, endomyocardial fibrosis)
4) Myocardial ischemia and infarction
5) Mitral or tricuspid valve stenosis
6) Pericardial disease (pericarditis, pericardial
tamponade)
What are the factors precipitating/exacerbating
heart failure?
1) Cardiac events
2) Noncardiac events
3) Nonadherence with prescribed HF medications or with dietary recommendations
4) Drugs
How can drugs precipitate or exacerbate HF?
1) Negative inotropic effects
2) Direct cardiotoxicity
3) Increased sodium and/or water retention
Which drugs have negative inotropic effects?
1) Antiarrhythmics
2) Beta-blockers
3) Calcium channel blockers
Which Antiarrhythmics have negative inotropic effects?
1) Disopyramide
2) Flecainide
3) Propafenone
Which Beta-blockers have negative inotropic effects?
1) Propranolol
2) Metoprolol
3) Carvedilol
Which Calcium channel blockers have negative inotropic effects?
1) Verapamil
2) Diltiazem
Which drugs can cause cardiotoxicity?
1) Doxorubicin
2) Epirubicin
3) Daunomycin
4) Ethanol
5) Cyclophosphamide
6) Trastuzumab
7) Bevacizumab
8) Ifosfamide
9) Lapatinib
10) Sunitinib
11) Imatinib
12) Amphetamines
13) Cocaine
Which drug contains high sodium?
Ticarcillin disodium
Which drugs can cause sodium and/or water retention?
1) NSAIDs
2) COX2-inhibitors
3) Rosiglitazone
4) Pioglitazone
5) Glucocorticoids
6) Androgens and Estrogens
7) High dose Salicylates
8) High sodium-containing drugs
___ and _____ are part of
CHF therapy.
Medication history; Discontinuation of medications known to exacerbate HF
What are key elements in the pathogenesis of progressive myocardial failure?
Left ventricular hypertrophy and remodeling
Ventricular remodeling is a broad term describing:
Changes in both:
1) Myocardial cells
2) Extracellular matrix
= changes in the size, shape, structure, and function of the heart.
What is the normal shape of the left ventricle?
Ellipse
What is the shape of the left ventricle after remodeling?
Sphere
The change in ventricular size and shape during remodeling further:
1) Depresses the mechanical performance of the heart
2) Increases regurgitant flow through the mitral valve
3) Sustains progression of remodeling
The onset of the ___ precedes
the development of HF symptoms.
Remodeling process
Which mediators play an important role in initiating the signal transduction cascade responsible for ventricular remodeling?
1) Angiotensin II
2) NE
3) Endothelin
4) Aldosterone
5) Vasopressin
6) Numerous inflammatory cytokines
The goals of therapy in management of chronic
HF are to:
1) Improve the patient’s quality of life
2) Relieve or reduce symptoms
3) Prevent or minimize hospitalizations
4) Slow progression of the disease
5) Prolong survival
The general principles used to guide the treatment of HFrEF are based on:
Numerous large, randomized, double-blind, multicenter clinical trials.
The guidelines for the management of HFpEF are based primarily on:
Studies in relatively small groups of patients and on clinical experience.
The complexity of the HF syndrome necessitates a comprehensive approach to management, which includes:
1) Accurate diagnosis
2) Identification and treatment of risk factors
3) Elimination or minimization of precipitating factors
4) Appropriate pharmacologic and nonpharmacologic therapy
5) Close monitoring and follow up
What is the first step in management of chronic HF?
Determine the etiology and/or precipitating factors
___ in patients with CHD may reduce HF symptoms.
Revascularization or anti-ischemic therapy
___ reduces cardiac workload and is recommended for all patients with acute congestive symptoms, until patient’s symptoms have stabilized and excess fluid is removed.
Restriction of physical activity
What may improve functional status & quality of life, and may reduce hospitalizations and death from cardiovascular causes?
Exercise training
In patients with hyponatremia (Na ˂130 mEq/L) or those with persistent volume retention despite high diuretic doses and sodium restriction, daily fluid intake should be:
Limited to 2 L/day from all sources.
You should be careful with sodium and fluid restriction in patients with:
HFpEF
Why should you be careful with sodium and fluid restriction in patients with HFpEF?
Because excessive restriction can lead to:
1) Hypotension
2) Low-output state
3) Renal insufficiency
What are the four identified stages of HF?
1) Patients at Risk for HF
2) Patients With Pre-HF
3) Stage C HF
4) Stage D (Advanced) HF
What is the first stage of HF? (Patients at Risk for HF)
Patients with cardiac disease but without limitations of physical activity
What interventions can be taken to prevent the first stage of HF from progressing?
1) If Hypertensive: Reduce BP
2) If type 2 diabetes: SGLT2i
3) Healthy life style habits
4) Risk factor identification and prevention
Risk factors act ___(additively/synergistically) to develop both HFrEF and HFpEF.
Synergistically
___ and ___ are recommended for HF prevention in patients with multiple cardiovascular risk factors.
ACE inhibitors/ARBs; Statins
What is the second stage of HF? (Patients With Pre-HF)
Patients with cardiac disease that results in slight limitations of physical activity.
Patients with the second stage of HF (Patients With Pre-HF) have:
Structural heart disease but NOT
HF symptoms.
What does structural heart disease include in patients with the second stage of HF (Patients With Pre-HF)?
1) Left ventricular hypertrophy
2) Recent or old MI
3) Valvular heart disease
4) LVEF ˂ 0.4
How can you prevent clinical HF in patients with Pre-HF (2nd stage) with LVEF ≤ 40%?
ACEIs should be used to prevent symptomatic HF and reduce mortality
How can you prevent clinical HF in patients with Pre-HF (2nd stage) with a history of MI or ACS?
Statins should be used to prevent symptomatic HF and adverse cardiovascular events.
How can you prevent clinical HF in patients with Pre-HF (2nd stage) with a history of MI or ACS and LVEF ≤ 40%?
Evidence-based beta blocker should be used to reduce mortality
Which drugs should not be used in patients with LVEF ≤50%?
1) Thiazolidindiones
2) Non-hydropyridine calcium channel blockers
What is the third stage of HF? (Stage C HF)
Patients with cardiac disease that results in marked limitation of physical activity.
Although patients are comfortable at rest, less than ordinary activity will lead to symptoms
Patients with structural heart disease and previous or current symptoms are classified as ___ and can have HFrEF or HFpEF.
Stage C
Patients with HF should receive vaccination for ___ to reduce mortality.
Respiratory illnesses
Patients with HF should be screened for ___ and other risk factors for poor self care.
Depression
Which drugs are recommended in patients with heart failure with fluid retention?
1) Loop diuretics
2) Metolazone (If no response)
In patients with HFrEF and NYHA class II-III symptoms, the use of ___ is recommended to reduce morbidity and mortality.
ARNi (angiotensin receptor/neprilysin inhibitor)
In patients with previous or current symptoms of chronic HFrEF, the use of ___ is beneficial to reduce morbidity and mortality when the use of ARNi is not feasible.
ACEIs/ARBs
ARNi should not be coadministered with __ or within ____.
ACEIs; the last 36 hours of the last dose of ACEIs.
ARNi should not be administered in any patient with a history of ___.
Angioedema
___ should not be administered in any patient with a history of angioedema.
ACEIs
In patients with previous or current symptoms of chronic HFrEF, use of one of the three ____ is recommended to reduce mortality and hospitalization
Beta blockers
In patients with HFrEF and NYHA class II-IV symptoms, which drug is recommended to
reduce morbidity and mortality if eGFR is > than 30 mL/min and serum potassium < 5 mEq/L?
Aldosterone receptor antagonist (Spironolactone or Eplerenone)
For African-American patients with NYHA class III-IV HFrEF who receive optimal therapy, the combination _____ is recommended to improve symptoms and reduce morbidity and mortality,
Hydralazine and Isosorbide dinitrate
In patients who can not receive ACEIs, ARNi or ARB, ___ is recommended to reduce morbidity and mortality.
Hydralazine and isosorbide dinitrate
For patient with symptomatic (NYHA class II-III) stable chronic HFrEF (≤ 35%) who are receiving GDMT, including beta blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of ≥ 70 bpm at rest, ___ can be beneficial to reduce heart failure hospitalization and cardiovascular death.
Ivabradine
In patients with symptomatic HFrEF despite GDMT (or who are unable to tolerate GDMT), ___ may be considered to decrease hospitalization for HF.
Digoxin
In selected high risk patients with HFrEF and recent worsening of HF already on GDMT an ____ may be considered to decrease HF hospitalization and cardiovascular death.
Oral soluble guanylate cyclase stimulator
Nonpharmacologic therapy with devices such as _____is also indicated in certain patients with HFrEF in Stage C.
1) Implantable cardioverter-defibrillator (ICD)
2) Cardiac resynchronization therapy (CRT) with a biventricular pacemaker
What is Stage D (Advanced) HF?
Patients with cardiac disease that results in an inability to carry on physical activity without discomfort.
Symptoms of congestive heart failure are present even at rest
In patients with advanced heart failure, when consistent with patient’s goal of care, timely
referral for HF specialty care is recommended to:
1) Review HF management
2) Assess suitability for advanced HF therapies (left ventricular assist device [LVAD], cardiac
transplantation, palliative care and palliative inotropes).
Guidelines for Stage D HFpEF recommend treating co-morbid
conditions by:
1) Controlling HR and BP
2) Alleviating causes of myocardial ischemia
3) Reducing volume
4) Restoring and maintaining sinus rhythm in patients with atrial fibrillation
What are the 3 treatment approaches for HFpEF?
1) Symptom-targeted treatment
2) Disease-targeted treatment
3) Mechanism-targeted treatment
What is the symptom-targeted treatment for HFpEF?
1) Decrease pulmonary venous pressure
2) Reduce myocardial oxygen demand
3) Maintain atrial contraction
4) Improve exercise tolerance
What is the rationale for decreasing pulmonary venous pressure in HFpEF?
Reduce left ventricular volume
What is the rationale for reducing myocardial oxygen demand in HFpEF?
1) Reduce HR
2) Control BP
What is the rationale for maintaining atrial contraction in HFpEF?
Restore sinus rhythm
Which agents can decrease pulmonary venous pressure?
1) Diuretics
2) Nitrates
3) Salt restriction
Which agents can reduce myocardial oxygen demand?
1) Beta-Blockers
2) Verapamil
3) Diltiazem
4) ACEi/ARBs
5) CCBs
Which agents can maintain atrial contraction?
Cardioversion of A-fib
Which agents can improve exercise tolerance?
Use positive inotropic agents with caution
What is the disease-targeted treatment for HFpEF?
1) Prevent or treat myocardial ischemia
2) Prevent or regress ventricular hypertrophy
Which agents can prevent or treat myocardial ischemia?
1) Beta-Blockers
2) Nitrates
3) Verapamil
4) Diltiazem
Which agents can prevent or regress ventricular hypertrophy?
Antihypertensives
What is the mechanism-targeted treatment for HFpEF?
1) Modify myocardial and extramyocardial mechanisms
2) Modify intracellular and extracellular mechanisms
Which agents can modify myocardial and extramyocardial mechanisms?
1) ACEis/ARBs
2) Diuretics
3) Spironolactone
Which agents can modify intracellular and extracellular mechanisms?
1) ACEis/ARBs
2) Diuretics
In patients with atrial fibrillation who are intolerant to or have NOT responded to a βblocker; ____ may be considered.
1) Diltiazem
2) Verapamil
A nondihydropyridine or dihydropyridine calcium channel blocker can be considered for ___.
Angina and hypertension
___ and __ are recommended for the treatment of both HFrEF and HFpEF.
β-blockers and diuretics
In HFpEF, β-blockers are used to:
1) Decrease HR
2) Prolong diastole
3) Modify hemodynamic response to exercise
In HFrEF, β-blockers are used in the long term to:
1) Improve the inotropic state
2) Modify LV remodeling
The doses of diuretics used to treat ___ are much smaller than those used to treat ___.
HFpEF; HFrEF
____ are useful in lowering BP and reducing LVH.
Antagonists of the RAAS
___ may be useful in the treatment of HFpEF.
Calcium channel blockers
Which calcium channel blockers are usefulin HFpEF?
1) Diltiazem
2) Amlodipine
3) Verapamil
The natriuretic peptides ANP and BNP cause:
1) Vasodilation
2) Natriuresis
3) Diuresis
What do the natriuretic peptides ANP and BNP do?
1) Inhibit renin secretion
2) Inhibit aldosterone production
3) Attenuate ventricular hypertrophy and fibrosis
What is Neprilysin?
A zinc-dependent metalloprotease
Function of Neprilysin?
1) Breaks down the natriuretic peptides ANP & BNP, bradykinin and other peptides
2) Clearance of amyloid-β from the brain and CSF
ARB/Neprilysin Inhibitor such as ___ can be used for the treatment of patients with HFrEF.
Valsartan/Sacubitril
___ is a prodrug, which inhibits the action of neprilysin.
Sacubitril
What are the adverse effects of Valsartan/Sacubitril?
1) Hypotension
2) Dizziness
3) Hyperkalemia
4) Worsening renal function
5) Cough
6) Angioedema
Valsartan/Sacubitril should not be used with:
1) ACEis or ARBs
2) Aliskiren
Valsartan/Sacubitril contraindications?
1) History of angioedema
2) Pregnancy
3) Hyperkalemia
4) Renal artery stenosis
5) Severe hepatic impairment
6) Renal dysfunction
7) Diabetic patients taking Aliskiren
Where does Ivabradine act?
Blocks the If current in the SA node that is responsible for controlling the heart rate.
What does Ivabradine do?
Slows the spontaneous depolarization of the sinus node = dose-dependent slowing of HR
Ivabradine’s effects are specific to the If current and does not affect:
1) Myocardial contractility
2) AV conduction
Ivabradine is extensively metabolized by intestinal and hepatic ___.
CYP3A4
Ivabradine is contraindicated in which patients?
1) Patients taking CYP3A4 inhibitors = bradycardia
2) Patients taking CYP3A4 inducers = prolongs QT
Adverse effects of Ivabradine?
1) Bradycardia
2) Effects on vision primarily manifesting as phosphenes (transient brightness in portions of the visual field)
3) Atrial fibrillation
In the heart, natriuretic peptides lead to the activation of the ___ pathway.
Nitric Oxide-soluble Guanylate Cyclase-cGMP
Soluble Guanylate Cyclase (sGC) stimulators activate:
sGC independent of NO by binding to a non-heme site in sGC
Which sGC stimulator has been in use for pulmonary hypertension?
Riociguat
What is Vericigaut?
sGC stimulator
Vericigaut has significant benefits in reducing hospitalizations in patients with ___ that are at high risk of cardiovascular events.
HFrEF
Does Vericiguat have a mortality benefit?
NO
Vericigaut is contraindicated in which patients?
1) Those with concomitant use of other soluble guanylate cyclase (sGC) stimulators
2) Pregnancy
Unless contraindicated, ___ should be initiated early as part of the foundational therapy in all patients with HF.
SGLT2 inhibitors
SGLT2 inhibitors have been shown to reduce risks of clinical events in patients with heart failure (HF), with early and sustained benefits regardless of:
1) Ejection fraction
2) Diabetic status
3) Care setting
Contraindications for SGLT2 inhibitors?
1) Type 1 DM or history of ketoacidosis
2) Hypotension (systolic BP<100mmHg)
3) Severe kidney disease (eGFR <20-25mL/min/1.73m2)
4) Pregnancy, risk of pregnancy, breast feeding
5) Caution in patients with a history of recurrent UGS infections
Association of ____ was the best combination for reducing all-cause death and the composite outcome of cardiovascular death or hospitalization for HF, and serious adverse renal outcomes in patients with a broad spectrum of severity of HFrEF.
1) ARNi
2) β-blockers
3) Aldosterone receptor antagonists
4) SGLT2 inhibitors
What should you monitor when giving SGLT2 inhibitors?
1) Check renal function when starting therapy and after 1-2 weeks
2) Blood glucose
3) Observe for acute illness or major surgery
Patient/caregiver counselling for SGLT2 inhibitors?
1) Ensure adequate daily genital hygiene
2) Watch for symptoms of volume depletion, urogenital infection, and diabetic ketoacidosis
3) Avoid dehydration, low carbohydrate (ketogenic) diet, and excessive alcohol consumption
What are the benefits of diuretics?
1) Reduction of symptoms associated with fluid retention
2) Improvement of exercise tolerance and quality of life
3) Reduction of hospitalizations from HF
4) Reduction of pulmonary and peripheral edema through reduction of preload
True or False:
Diuretics prolong survival and alter disease progression.
False
Over-diuresis may produce __ with ACE inhibitor or β-blocker therapy.
Hypotension
Hypotension can be a significant problem in the treatment of HFpEF because:
A small change in volume causes a large change in filling pressure and cardiac output.
___(Loop/Thiazide) diuretics may be preferred in patients with mild fluid retention and elevated BP because of their
more persistent antihypertensive effects.
Thiazide
____ or ____ can inhibit delivery of loop diuretics to their site of action and decrease effectiveness.
1) Probenecid
2) Organic by-products of uremia
Loop diuretics should not be given with:
NSAIDs
Unlike thiazides, loop diuretics maintain their effectiveness in the presence of:
Impaired renal function
The most common cause of HFrEF is:
Ischemic heart disease
Which ACEi’s benefit post-MI patients whether therapy is initiated early or late after the infarct?
1) Captopril
2) Ramipril
3) Trandolapril
CKD patients should be monitored carefully for the development of:
1) Worsening renal function
2) Hyperkalemia
True or False: ACEi’s improve survival rate.
True
Do ARBs cause cough or angioedema?
No
Do ACEi’s cause cough or angioedema?
Yes
Which drugs are ARBs?
1) Candesartan
2) Losartan
3) Valsartan
ARBs are indicated in which patients?
Those who are unable to tolerate cough produced by ACE inhibitors.
____ should be used in all stable patients with HF and a reduced left ventricular EF in the absence of contraindications.
β-blockers
___ are recommended for asymptomatic patients with a reduced left ventricular EF to decrease the risk of progression to HF.
β-blockers
Three β-blockers have been shown to significantly reduce mortality compared with placebo:
1) Carvedilol
2) Metoprolol succinate (CR/XL)
3) Bisoprolol
What have the 3 main β-blockers been shown to do?
Reverse modeling:
1) Decrease ventricular mass
2) Reverse the sphericity of the ventricle
3) Reduce systolic and diastolic volumes
What does reverse modeling mean?
Return of the heart toward more normal size, shape, and function
Initiating a β-blocker first may be of benefit for which patients?
1) Those with evidence of excessive SNS activity (tachycardia)
2) Those whose renal function or potassium concentrations preclude starting an ACEi (or ARB) at that time
The risk for decompensation during β-blocker initiation may be greater in the absence of:
Preexisting ACE inhibitor therapy
β-Blockers favorable effects include:
1) Antiarrhythmic effects
2) Attenuating or reversing ventricular remodeling
3) Decreasing myocyte death from catecholamine-induced necrosis or apoptosis
4) Preventing fetal gene expression
5) Improving left ventricular systolic function
6) Decreasing HR and ventricular wall stress thereby reducing myocardial oxygen demand
7) Inhibiting plasma renin release
β-blockers should NOT be started in patients on:
IV inotropic support
How should β-blockers be started?
1) In very low doses with slow upward dose titration (not ˂ 2 weeks)
2) Close monitoring to minimize acute decompensation
Dose up-titration is a __(long/short) process.
Long
In patients with HFpEF, How might β-blockers help lower and maintain low pulmonary venous pressure?
By decreasing HR and increasing the duration of diastole
Why is tachycardia poorly tolerated in patients with HFpEF?
Because rapid HRs cause an increase in myocardial oxygen demand and a decrease in coronary perfusion time, which can promote ischemia even in the absence of epicardial CAD
Excessive bradycardia when using beta-blockers can result in:
A fall of cardiac output despite an increase in LV filling
Which aldosterone antagonists have potassium sparing effects?
1) Spironolactone
2) Eplerenone
Aldosterone antagonists inhibit ____, thereby attenuating cardiac fibrosis and ventricular remodeling.
Cardiac extracellular matrix and collagen deposition
What are the most common adverse effects of Spironolactone?
1) Gynecomastia
2) Hyperkalemia
What is the most common adverse effect of Eplerenone?
Hyperkalemia
There are NO clear guidelines on aldosterone antagonist use for patients with:
HFpEF
What are the factors contributing to the high incidence of hyperkalemia with aldosterone antagonists?
1) The initiation of aldosterone antagonists in patients with impaired renal function or high serum K+
2) The failure to decrease or stop potassium supplements when starting aldosterone antagonists
3) Diabetes mellitus
4) High potassium intake with food
5) Concomitant use of ACEi/ARBs and NSAIDs.
Strategies for reducing the risk for hyperkalemia with aldosterone antagonists:
1) Avoid starting aldosterone antagonists in patients with abnormal labs
2) Start with low doses
3) Decrease or discontinue potassium supplements when starting an aldosterone antagonist
4) Avoid concomitant use of NSAIDs (COX-1 or COX-2 inhibitors) or high-dose ACEi or ARBs
5) Monitor serum K+ and renal function
6) If K+ exceeds 5.5 mg/dL at any point during therapy, reduce or stop aldosterone antagonist therapy
What abnormal labs prevent you from starting aldosterone antagonists out of fear of hyperkalemia?
1) Serum creatinine concentration >2.0 mg/dL in women or >2.5 mg/dL in men or a CrCL <30 mL/min
2) Recent worsening of renal function
3) Serum K+ >5 mEq/L
4) History of severe hyperkalemia
How should you counsel patients taking aldosterone antagonists?
1) Limit intake of high potassium-containing foods and salt substitutes
2) Avoid the use of over-the-counter NSAIDs
3) Temporarily discontinue aldosterone antagonist therapy if diuretic therapy is interrupted
__ and __ are combined in the treatment of HFrEF because of their complementary hemodynamic actions.
1) Nitrates
2) Hydralazine
Nitrates cause:
Venodilation = decrease preload
Hydralazine causes:
Arterial vasodilation = decreased afterload
Hydralazine is a:
Direct-acting arterial vasodilator
Nitric oxide attenuates myocardial remodeling by reducing:
1) Cardiac myocyte hypertrophy
2) Cardiac dilation
3) Mortality
Digoxin has a:
Positive inotropic effect on the heart
What is the benefit of digoxin on hospitalizations and mortality?
NONE
True or False: Digoxin is a first line agent in HF.
False
There is NO established role for Digoxin in ___ when patients are in normal sinus rhythm.
HFpEF
What does Digoxin help control?
Ventricular response in patients with HFrEF and supraventricular arrhythmias
