Download Heart Failure Related Deaths - 5

Chronic Heart Failure - Part 1
Objectives - 2
• Understand the impact to society
• Review risk factors for developing Heart failure (HF)
• Briefly describe the pathophysiology
• Review evidence for each medication class
• Discuss when and how to initiate each medication class
• Review proper follow-up labs and assessment after starting medications
• Describe common adverse effects and options regarding treatment
Heart Failure Epidemic - 3
• More than 5 million people in the United States have HF – Approximately 550,000 new diagnoses occur
every year – Leading cause of hospitalization among Medicare beneficiaries (elderly patients) – Over 37
billion dollars spent of the management of HF – 1 in 8 deaths has HF mentioned in the death certificate
Trends in Cardiovascular Disease - 4
• Over the last few decades there has been a trend in cardiovascular disease with new treatments,
medications, and good combination of medications.
• Due to these improvements deaths from cardiovascular disease has been reduced.
• However, because these patients are living longer there is an increased risk for these patients having
heart failure, and hospital discharge for HF continues to rise, because patients are surviving a post-MI.
Heart Failure Related Deaths - 5
★ Heart Failure (HF) is the end-stage of cardiac disease – Without appropriate therapies and good
compliance with medications HF can be as devastating as cancer – Mortality rate is approximately 10%
per year after diagnoses (3 yrs 30%, 5 yrs 50%, and at 10 yrs 80-90% are dead) – Data suggests that
mortality rate may be decreasing – Survival rate is lower for men than women.
Heart Failure Defined - 6
• Heart failure is easily defined, but difficult to treat
• “Heart failure is a complex clinical syndrome that can result from any structural or functional
cardiac disorder that impairs the ability of the ventricle to fill with or eject blood.”
Heart Failure: More than Just the Left ventricle or Low Ejection Fraction - 7
Left Ventricle HF
• HF with reduced EF (usually EF ≤ 45%) – This is the type mostly associated with heart failure
• Heart failure is subclassed as Asymptomatic (ALVD) OR Symptomatic, and treatment is based upon
whether a patient is having symptoms or NOT.
HF with preserved EF (usually EF > 45%)
• Caused from diastolic dysfunction (impaired relaxation) AND HF symptoms are present
Right Ventricle HF
• Ejection fraction cannot be obtained in right heart failure
• Ejection Fraction (EF) is qualitatively assessed as mild, moderate, or severely reduced
• Causes could include: ACS in the RCA, PE, severe lung disease, severe sleep apnea. These all can cause
pressure on the right side of the heart leading to it’s failure.
Risk Factors for the Development of HF - 8
• Major
• Age, HTN, myocardial infarction (MI), Diabetes mellitus (DM), Valvular heart disease, Obesity
• Minor
• Excessive alcohol intake, Cigarette smoking, Dyslipidemia, chronic kidney disease (CKD), Anemia,
obstructive sleep apnea (OSA)
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Risk versus surrogate
• Tachycardia, Microalbuminuria, ↑ Inflammatory markers, ↑ Natriuretic peptides
Toxic precipitants
• Chemotherapy, Cocaine, NSAIDs, TZDs
Other Common Risk Factors of HF - 9
• TREATING the underlying condition (nutritional, HIV) may improve the HF
• Cardiomyopathies
• HCM, DCM, RCM, ARVC
• Nutritional
• Thiamine, selenium
deficiency
• Cachexia
• Other
• HIV
• Endocrine
• Hypo/hyperthyroidism
• Cushing syndrome
• Adrenal insufficiency
• Infiltrative
• Sarcoidosis
• Amyloidosis
• Hemochromatosis
Compensatory Mechanisms in HFrEF - 10
Heart failure with reduced ejection fraction (HFrEF)
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The pathophysiology of heart failure include many compensatory mechanisms that occur in HRrEF,
and it may also occur in heart failure with preserved ejection fraction (EF).
• An example would be when a patient has an acute coronary syndrome (ACS) and their ejection
fraction goes from being normal to < 20% which would cause the patient to have an immediate
reduction in cardiac output (CO). The body will then try to compensate by increasing CO through a
number of mechanisms.
The first mechanism would be to activate the
sympathetic nervous system (SNS) and release
norepinephrine (NE) into the system.
• This will increase heart rate and contractility
increasing CO.
The second mechanism would activate the renin
angiotensin aldosterone system (RAAS) by releasing
angiotensin II (Ang II), and aldosterone which
vasoconstricts the periphery leading to sodium and
water retention through mechanisms in the kidney.
• This increases blood pressure to increase preload
in the heart.
The third mechanism is vasoconstriction by
releasing NE, Ang II, Vasopressin, and Endothelium-1 systemic vascular resistance (SVR) increases
and redistribution of blood to the Central vascular system (CVS) occurs.
All of these mechanisms result in reduced CO from ventricular remodeling.
• This all results in increased death, arrhythmias, sudden cardiac death, and other things associated
with HF
The Physics of Heart Failure - 11
This is very important in understanding why patients have symptoms and in the treatment of HF.
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CO = stroke volume (SV) x heart rate (HR)
BP = cardiac output (CO) x Peripheral vascular resistance (PVR)
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The Frank Starling Curve
• In a normal person when the body senses a low CO it tries to increase preload, and as preload is
increased so also is stroke volume which ultimately results in increased cardiac output
• CO = stroke volume (SV) x heart rate (HR)
• In a patient with HFrEF the curve is shifted down which means the heart tries to increase stroke volume
by increasing preload BUT this occurs only to a certain point and then the curve starts to flatten and
once the dashed line (LV end-diastolic pressure ~15-18) is crossed the patient becomes symptomatic
with orthopnea or shortness of breath.
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Another important part of physics
of the heart in treatment is the
relationship between stroke
volume and afterload.
Afterload represents peripheral
vascular resistance (PVR) in the
BP equation.
• BP = cardiac output (CO) x
Peripheral vascular
resistance (PVR)
In a normal patient if there is a
reduced afterload (PVR) blood
pressure is also reduced, and
larger changes in afterload are
needed to have a smaller change
in stroke volume
In patients with moderate HF the curve shifted down and smaller changes in afterload result in
increases in stroke volume
In patients with severe HF the curve gets more vertical and smaller
changes in afterload results in larger changes the stroke volume
This is important as we think about medications used in heart failure.
• Ace inhibitors will reduce afterload and increase stroke volume
in a patient with severe HF with a reduced ejection fraction. When
this occurs and the HR stays the same. There is an increase in
stroke volume therefore an increase in cardiac output just by
reducing afterload.
Small increases at appropriate intervals is not likely to affect blood pressure much as it would be in the
case of a patient with a normal ejection fraction OR in the general treatment of HTN.
The American Heart Association has recently focused more on stages of heart failure instead of
symptoms of heart failure.
When a patient progresses from Stage A → Stage B there is no going back to stage A
Stage A - 14
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Stage A = Patients who are at risk of heart failure
Prevention in this stage is very important in reducing mortality
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There are many major trials in terms of using medications to prevent mortality in a patient with reduced
ejection fraction
The reason patients in these trials have heart failure was mostly due to ischemia from coronary artery
disease (CAD) – prevent CAD most likely prevents heart failure
One exception in these trials listed was the A-HeF trial where African-Americans were using
Hydralazine versus Isosorbide dinitrate to prevent heart failure from hypertension.
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Stage A – Prevention of HF through 1° & 2° CAD prevention
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Smoking cessation
Lipid management
Blood pressure control
Physical activity
Weight management
• Diabetes management
• Appropriate medications
• Beta-blockers, Renin-Angiotensin-Aldosterone system (RAAS) blockers,
antiplatelets, statins, influenza vaccination
HOPE Study Primary Outcome and Tertiary HF Outcomes - 17
• The HOPE Study used ramipril in patients who were at risk for cardiovascular disease
• This trial showed a reduction of about 3.8% in the primary outcome which typically includes reduction
in cardiovascular deaths, nonfatal MI, and stroke.
• This trial proved that using an ace inhibitor was very important in reducing cardiovascular events.
• A tertiary outcome observed new onset heart failure, and showed that those patients on placebo
developed HF 20% greater than those on an Ace inhibitor (ramipril).
★ It would be reasonable to treat a patient who does not have heart failure with an Ace inhibitor to
prevent HF from occurring if they have HBP or certain risk factors.
Stage A – Prevention of HF - 18
Poor Awareness, Control, and Treatment of HTN
• We know from the American Heart Association that most patients are aware that they have
hypertension and the majority are treated, BUT patients are still not controlled with their blood
pressure.
• This is probably due to noncompliance with medications, clinicians not increasing medications
because of worries of adverse effects, diets high in salt, etc.
★ Control blood pressure, and the number of heart failure cases will reduce.
ALLHAT HF Outcomes - 19 (study that was the basis for JNC-7)
• This study used 4 drugs for the treatment of hypertension (Chlorthalidone, lisinopril, amlodipine, and
doxazosin). The doxazosin arm was stopped early because of a higher incidence of heart failure.
• Definitely do not use an alpha blocker for monotherapy in the treatment of hypertension, because
this will worsen the incidence of heart failure
Patients
hospitalized with heart failure was reduced more with Chlorthalidone (may have masked
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symptoms of heart failure longer) versus an Ace inhibitor or a Calcium Channel Blocker.
★ Any of the 3 can be used in HF patients, because there was no difference in mortality
HYVET – Treatment of Hypertension in the Elderly - 20
• It is still unknown what hypertension goals is needed in patients over the age of 80
• This trial used an Indapamide-based regimen versus Placebo to get blood pressure < 150/80
• The primary outcome of cardiovascular death showed a nonsignificant reduction with patients on
Indapamide versus placebo
• However, there was a significant reduction in the number of patients with new onset heart failure (64%
RRR) - HUGE!
★ It would be reasonable to treat the patient over the age of 80 with a thiazide-based regimen to a goal of
< 150/80 to prevent heart failure.
Stage B - 21
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Stage B = Heart failure with cardiac structural abnormalities or remodeling causing a low ejection
fraction without symptoms
Goals = prevent further remodeling and Delay HF Onset
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How do we identify these patients? - 22
• Typically, these patients are found Post-ACS
• Patients are admitted with chest pain / changes on their EKG, and go to the Cath Lab for Heart
catheterization and/or echocardiogram
• In Cath lab patient may receive angiography, stenting, or coronary artery bypass graft (CABG)
Can be screened
• Brain natriuretic peptide (BNP) or NT-proBNP – this is a hormone that is released from the heart in
response to an increased preload (stretch) which causes a positive inotropic effects. It is also a
vasodilator, and a diuretic which tries to get rid of the excess fluid.
• Echocardiogram – standard test to assess ejection fraction in patients with heart failure
• Strong family history of cardiovascular disease may need echocardiogram screening
• Receiving cardiotoxic medications (e.g. breast cancer) screen using echocardiogram every 3 months
or at least annually.
Stage B - Treatment -23
What needs to be done once a stage B heart failure patient is found?
• Patient that is Post-ACS
• Treated following the ACC/AHA guidelines which includes:
- RAAS inhibitor (Ace
inhibitor/ARB), β-blocker,
statin, ASA
• Patient that has reduced ejection
fraction due to supraventricular
arrhythmias or atrial fibrillation
• Then control rate or convert to
normal sinus rhythm (NSR)
Severe
valvular disease
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• Follow ACC/AHA guidelines –
Fixing the valve corrects the heart
failure
Reduced
EF with no symptoms
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★ All Class I recommendations that
apply to Stage A patients PLUS – RAAS inhibitor and β-blocker
RAAS In Heart Failure - 24
• From compensatory mechanisms there is an increase in renin and angiotensin II
• Angiotensin II can bind to the AT I receptor causing:
• Vasoconstriction
• Cell growth
• Sodium and water retention
• Activation of the sympathetic nervous system (SNS)
• Angiotensin II can also bind to the AT II receptor and may have beneficial effects which may be
important in using an ARB.
• These effects include: vasodilation, anti-proliferative, increase Kinins, and increase nitric oxide
• The bradykinin system is also associated with the RAAS. Bradykinin can be broken down into inactive
peptides AND potentiate nitric oxide increasing vasodilation, decreasing ischemia, decreasing platelet
aggregation, and having a positive inotropic effect.
• Medications are used to inhibit this system which is hyperactive in heart failure they include:
• Renin Inhibitors – Inhibits the conversion of angiotensinogen → angiotensin I
• Ace inhibitors – Inhibits the conversion of angiotensin I → angiotensin II
- This may not be the main mechanism in heart failure because angiotensin II levels while
elevated at the beginning will be reduced with an Ace inhibitor.
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However, they usually go back to baseline levels after months of treatment with an Ace
inhibitor.
- This is because of non-Ace pathways where angiotensin II can be created. This pathways
includes the chymase pathway
- The likely effect of Ace Inhibitors is the benefits from the breakdown of bradykinin
- Unfortunately, the increase of bradykinin exhibits the adverse affect of COUGH and
angioedema may also be associated with bradykinin potentiation.
- ARBs will block the AT I receptors and the negative effects, AND potentially leaving more
angiotensin II to bind to the AT II receptor (although this is less clear)
• Aldosterone antagonist include Spironolactone, and Eplerenone – β-blockers also inhibit RAAS
Stage B – Treatment with ACE inhibitors
• Class IA – ACEIs should be used in all patients with a recent or remote history of MI regardless of EF
or presence of HF.
• Captopril (SAVE), ramipril (AIRE), trandolapril (TRACE)
• Class IA – ACEIs should be used in patients with a reduced EF and no symptoms of HF, even if they
have not experienced MI.
• Enalapril (SOLVD-prevention)
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SOLVD-Prevention Trial - 26
• In this trial included placebo versus enalapril whether they had symptoms or not
• Patients received enalapril 2.5 mg twice a day
• The primary outcome was death, or re-hospitalization for heart failure
★ Results: Enalapril reduced the primary outcome by ~ 29%
• Other components included reduction of the development of HF, multiple hospitalization for HF, etc.
Stage B – Treatment with ARBs - 28
• Class IB - An ARB should be administered to post-MI patients without HF who are intolerant of
ACEIs and have a low left ventricular ejection fraction (LVEF).
• Valsartan (VALIANT trial) – gave the ARBs a Class 1B recommendation
• Class IIA - ARBs can be beneficial in patients with low EF and no symptoms of HF who are intolerant
of ACEIs.
VALIANT Trial - 29
• The valiant trial was a Post-MI trial
• Patients came into the hospital with ACS and within 14 days were randomized to either valsartan,
captopril, or the combination of both.
• The results showed no difference between captopril (ACEI) versus valsartan (ARB). Valsartan was
deemed non-inferior to captopril, AND there was no benefit in the combination (dual RAAS inhibition)
Ace inhibitor/ARB. The combination would also increase adverse effects such as hyperkalemia, renal
dysfunction, etc.
• The complications of CV death, Re-MI, or hospitalization for HF showed no difference in the 3
treatment groups
★ Valsartan can be used in lieu of captopril, but most clinicians use ace inhibitors first because they are
cheaper and stronger evidence, BUT can be used as an alternative if patient has allergy to Ace inhibitor
How to Use an ACEI or ARB - 30
★ Always check renal function and electrolytes at baseline
• Consider contraindications
• Hx angioedema, Bilateral RAS, Serum K+ > 5.0 mmol/l, SCr > 2.5 mg/dl, severe Aortic Stenosis
(AS)
• May be used in patients with a SCr > 2.5, but be cautious and use low doses
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In Severe Aortic stenosis the aortic valve is much smaller which causes difficulty in pushing blood
into the vasculature and by vasodilation the heart is unable to compensate causing the patient to
become symptomatic with syncope because of low blood pressure
• If the patient is already on an Ace inhibitor they usually remain on medication as long as they are
not having worsening renal function or symptomatic.
• Clinicians are very cautious when starting and ACEI if patient has AS
Know common initiation and titration doses
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ACEI / ARB
Starting dose
Target dose
Enalapril
2.5 mg bid
10 mg bid
Captopril
6.25 mg bid
50 mg bid
Ramipril
2.5 mg daily
5 mg bid
Trandolapril
0.5mg daily
4 mg daily
Valsartan
40 mg bid
160 mg bid
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Consider dose increase every 2-4 weeks
• Consider every 4 weeks IF the patient’s blood pressure is on the lower side
• These medications are not being used to treat hypertension, but are trying to reverse the
compensatory mechanisms that have occurred because of low cardiac output
• If blood pressure is on the low side (SBP 103 - 98) and not symptomatic it would be reasonable to
increase the dose to the optimal target dose
• Most trials of patients that had HFrEF needed up titration.The doubling of the dose was done IF
the patient’s systolic blood pressure was > 90/60 (maybe even lower)
• Recheck renal function and electrolytes in 1-2 weeks after dose initiation or titration
• Aim for evidence-based target dose
• Once stable, recheck renal function and electrolytes at 1, 3, and 6 months, then q6months thereafter
Common problems
• Cough – switch to ARB
• Be cautious – patient may have upper respiratory tract infection, COPD exacerbation, or volume
excess
• ACEI induced cough is usually a dry/hacking that usually occurs at night and can occur either at the
beginning of treatment or years later
• Switching to another Ace inhibitor will not eliminate the cough
• Hyperkalemia
• Check for other offenders (e.g. Bactrim/Septra)
• If < 6.0 mmol/l and > 5.5 mmol/l – half-dose
• If > 6.0 mmol/l puts the patient at increased risk of ventricular arrhythmias - discontinue ACEI
- Bring the potassium down with 15 g of kayexalate x 2 and consider restarting at the lowest dose.
• SYMPTOMATIC hypotension
• Reduce diuretic or other antihypertensives first
• May reduce dose or discontinue if absolutely needed
• Worsening renal function
Worsening Renal function - 32
• If SCr Increases
• Check for other nephrotoxic meds
• If SCr increases up to 30% from baseline this may be acceptable
• May half or discontinue based on relative increase or absolute value
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Scenario A – labs after 1 week there is an
increase in SCr from 1 → 1.3 which should
catch the clinician’s attention to check labs
sooner – at 2nd week the SCr goes from 1.3
→ 1.6 clinician should consider if patient
has an underlying condition that is
predisposing them to renal failure with an
Ace inhibitor (bilateral renal artery
stenosis)
This is a 60% increase from baseline STOP
ace inhibitor and reevaluate the patient
Scenario B – patient has chronic kidney
disease (CKD) at baseline with a SCr of
1.7 start ACEI/ARB, and typically what is
seen is a patient’s SCr will increase only slightly to maybe 1.9 which is < 30%, and we will continue the
Ace inhibitor. This reduces renal filtration pressure and protects the kidneys
Scenario C – patient with normal SCr (0.9-1) typically will not see an increase, but still do not up
titrate dose sooner than every 2 weeks
• IF SCr increases unexplainably always look at the diuretic and discontinue 1st especially if the
patient is not symptomatic.
• If there is a HUGE increase STOP ace inhibitor/ARB
• If slight increase (40% from baseline) half dose or hold dose for couple days and go back to
previous dose (before titration) also have patient drink more water if the increase was diuretic
induced then restart at half dose. Definitely reduce the dose
Stage B – Treatment with β-Blockers - 33
• Class IA - β-blockers should be used in all patients with a recent or remote history of MI regardless of
EF or presence of HF.
• Atenolol, metoprolol tartrate, carvedilol, propranolol, timolol
• Class IB - β-blockers are indicated in all patients without a history of MI who have a reduced LVEF
with no HF symptoms.
• Carvedilol (CAPRICORN)
CAPRICORN Study - 34
• In the CAPRICORN study patients with a low ejection fraction with no symptoms were randomized to
carvedilol versus placebo.
• The starting dose of carvedilol was 6.25 mg BID (typical starting dose in HF is 3.125 mg BID)
• Results: All cause mortality or CV hospitalization was reduced BUT not statistically significant this may
have been caused by the dose being too high to start with and decompensated the patient
• Start carvedilol at a safer 3.125 mg BID
★ All cause mortality was significantly reduced in this patient population giving it a Class IB
recommendation
How to use a β-blocker – 35
• Patient must be stable!!!!!
• However, strongly advised to initiate prior to hospital discharge
• Consider contraindications
• Asthma, second or third degree heart block, sick sinus syndrome, sinus bradycardia (< 50 bpm)
• If the patient has uncontrolled asthma then get asthma under control then use a beta-1 selective agent
• If patient has 2nd or 3rd degree heart block, sick sinus syndrome, or sinus bradycardia without a
pacemaker be very cautious when using beta blockers and most likely not use them
• Start low…go slow
• Carvedilol 3.125 mg bid
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Double the dose every 2 weeks – maybe monthly in unstable patients
Aim for evidence-based target dose
• Carvedilol 25 mg bid
• Carvedilol 50 mg BID may be reasonable IF BP is still uncontrolled or patient is having ventricular
arrhythmias
Common problems
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• Symptomatic hypotension
• Worsening HF
• Bradycardia
• Fatigue
Stage C - 36
Patients with Symptoms or Prior Symptoms of HF and Structural Cardiac Dysfunction
Goal is to Minimize HF Symptoms AND Prolong Survival
Symptoms – Forrester Classification - 37
• On the y-axis is cardiac index which is cardiac output standardized to the body surface area
• On the x-axis is pulmonary capillary wedge pressure or left ventricular end-diastolic wedge pressure
both are the same.
• If the patient is compensated “normal” then they are in the upper left-hand quadrant of “warm and
dry”
• If the patient has Congestion (holding onto water) they are classified as “warm and wet”
• Wet symptoms include:
• Dyspnea, Orthopnea (SOB while laying down), paroxysmal nocturnal dyspnea (PND), Fatigue, and
anorexia due to volume in the stomach
• Poor perfusion are termed “cold and dry” cold symptoms are not common in patients with a reduced
CO unless severe
• Symptoms include confusion, weakness, cold periphery – for severe patients checked renal and
liver function also lactate levels which checks for organ perfusion
The
highest mortality is in patients who are “cold and wet” because of a severely reduced CO and
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volume overload. These patients have both Poor perfusion and Congestion
Signs Associated with Symptoms - 38
Clinical Feature
Symptoms
Signs
Congestion
Dyspnea, orthopnea, PND,
Fatigue, and anorexia
Bilateral lower extremity edema (BLEE), ascites,
hepatomegaly, anasarca (overall swelling), ↑ JVD
(strongest predictor), pulmonary edema, cachexia
Severe congestion
Severe dyspnea at rest
Crackles, rates, plural effusion, tachypnic, tachycardia
Poor perfusion
Confusion, weakness, cold
periphery
Pallor, Low SBP, anuria, or oliguria (organ failure)
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Assessment of Symptoms – NYHA Classification - 39
Class I
No limitation of physical ability.
Ordinary physical activity does not cause HF symptoms.
Class II
Slight limitation of physical ability. Ordinary physical activity results
in symptoms.
Class III
Marked limitation of physical ability. Comfortable at rest, but less
than ordinary physical activity results in symptoms.
Class IV
Symptoms at rest
Warning Signs or Symptoms of HF - 40
Hospitalization recommended
• Acute HF
• NYHA class IV symptoms, hypotension, worsening renal function, altered mental status (AMS)
• Acute coronary syndrome (ACS)
• Acute angina, chronic angina not relieved by NTG, progressive dyspnea not associated with excess
volume
• Other
• Uncontrolled arrhythmia, Low O2 sats (< 90%), ICD firing and unstable
Hospitalization considered
• Worsening congestion
• S/Sx of pulmonary or systemic congestion
• Electrolyte disturbances – K+ = 2.9 are increase risk of arrhythmias
• ICD firing and stable – see within 1 week on one learning, but if fires twice admitted to hospital
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