Congestive Heart FailureCongestive Heart Failure

Arun Abbi M.D.

OutlineOutline

1. Classification and epidemiology2. Pathophysiology3. Diagnosis4. Treatment5. Conclusions

ClassificationClassification

New York Heart Association classification (NYHA)

I – Asymptomatic with ordinary physical activity II- Symptomatic with ordinary physical activity III- Symptomatic with less than ordinary physical

activity IV – symptomatic at rest

EpidemiologyEpidemiology

Congestive heart failure is the leading cause of admissions over the age of 65

Affects 2% of the populationIncidence rises with age - affects 10% of

those over 80Overall 5 year mortality is 50%For Class IV – 1 year mortality is 35%

PathophysiologyPathophysiology

Impairment of LV function leads to decreased cardiac output and activation of neurohormonal compensatory mechanisms which accelerate the progression of CHF

This has been the focus of research and treatment over the last decade

Neurohormonal MechanismsNeurohormonal Mechanisms

1. Sympathetic system activation2. Activation of the Renin-Angiotensin

Aldosterone system (RAAS)3. Increased naturetic peptides4. Increased Antidiuretic hormone5. Increased Endothelins

Sympathetic ActivationSympathetic Activation

Causes increased cardiac output, increased heart rate, and peripheral vasoconstriction

If sustained activates the RAAS which increases both preload and afterload

Stimulation of alpha and beta receptors leads to myocardial hypertrophy and fibroblast hyperplasia which lead to decreased compliance

Increased norepinephrine levels lead to myocardial cell death and areas of focal necrosis further impairing LV function

Renin - Angiotensin Renin - Angiotensin Aldosterone System (RAAS)Aldosterone System (RAAS)

Stimulation leads to increased Angiotensin II which leads to :

1. Increased aldosterone 2. Increased norepinephrine 3.Inhibition of vagal tone

AldosteroneAldosterone

Shown to be elevated up to 20 times in patients with CHF

Causes growth promoting activity in nonepithelial cells

Stimulates fibroblasts which leads to interstitial and perivascular fibrosis which increases LV stiffness

Produced in nonrenal sites such as the vessels and heart

Up to 40% of patients will have elevated levels despite being on ACE inhibitors

Naturetic PeptidesNaturetic Peptides

3 types 1. Atrial Naturetic Peptide (ANP) – released from

the atria in response to stretch. Is very sensitive and will be released even with exercise. Causes naturesis and vasodilatation

2. Brain Naturetic Peptide (BNP) – release from the venticles in response to elevated LVEDP. Has the same effect as ANP

Naturetic Peptides cont’dNaturetic Peptides cont’d

3. C-type naturetic peptide – limited to the vascular endothelium and has limited effects on naturesis and vasodilatation

Antidiuretic HormoneAntidiuretic Hormone

Is elevated in severe heart failureHigher levels have been reported in patients

on diureticsCan lead to hyponatremia

EndothelinsEndothelins

Secreted by vascular endothelial cells Potent vasoconstrictor peptide which leads

to sodium retentionIncreases in proportion to the hemodynamic

severity of heart failureInterest in developing endothelin receptor

antagonists

DiagnosisDiagnosis

History – orthopnea and dyspnea are the best symptoms but are not very sensitive

Physical – S3, tachycardia and elevated JVP are specific but not sensitive

EKG – will be abnormal 90% of the time CXR – cardiomegaly does not correlate with acute

decompensation. Will show signs of redistribution if CHF is significant

ECHO- excellent test but expensive and difficult to obtain

Troponin - can predict a cause of the CHF

BNP BNP

New polypeptide that is produced in the ventricles Released in proportion to LV expansion reflecting

the LVEDP Levels rise with age (due to increased LV

stiffness) Levels are elevated with pulmonary disease (due

to increased RVEDP) Levels are elevated in end-stage renal disease

reflecting decreased excretion

BNPBNP

There is a bedside test that is FDA approved, but it costs $25 - $40 per test.

Cut off has been determined retrospectively in studies

Levels below 75 – 100 pg/ml correlate with fairly normal LV function

The higher the level the worse the LV function If a patient presented with acute worsening, one

would expect a level > 300 pg/ml

This test will probably be used to also follow therapy for patients. Studies have shown that better optimization of ACE therapy can be instituted.

It may reduce the need for repeat ECHO’s Levels rise acutely and decline with effective

treatment within hours – the ½ life is 22 minutes in patients without renal disease

BNPBNP

The best use is in patients with multiple medical problems who present with increased dyspnea.

If patients have COPD, are at risk for PE and have a history of CHF then BNP can help separate cardiac from other causes of dyspnea

Therapy Therapy

Acute emergency therapy

Chronic maintenance therapy

Acute Emergency TherapyAcute Emergency Therapy

1. Nitrates2. Diuretics3. Ace Inhibitors4. Morphine

NitratesNitrates

Decreases preload and afterload (slightly)Shown to be effective in reducing mortality

and improving symptomsCan be given sublingual, IV, or as a patchDose is 10mcg/min and can be titrated up

every 3 – 5 minutes until desired effect. Can cause hypotension

NitratesNitrates

Can switch to a patch from IV nitrates, however this switch worked only when patients were on lower doses (< 50 mcg/ml)

Topical patches have an onset in decreasing PCWP at 20 – 30 minutes with peak effect at 120 minutes. Therefore, their use in an acute severe decompensation is not warranted as first line therapy

NitratesNitrates

Sublingual NTG tabs decreased PCWP by 36%. Onset was 4 minutes with peak effect at 9 minutes

The spray had an onset of 1-2 minutes with peak effect at 5 minutes

DiureticsDiuretics

Have venodilatory properties as well as decreasing intravascular volume through diuresis.

Causes increased plasma renin and Norepinephrine levels leading to Increased SVR

A study comparing high dose NTG and low dose diuretics showed lower mortality than high dose diuretic and low dose NTG

Ace InhibitorsAce Inhibitors

Captopril sublingually decreased PCWP after 10 minutes with a peak effect seen at 30 minutes.

Sacchetti et al showed that it decreased the admissions to ICU – odds ration 0.29

MorphineMorphine

Causes venodilation through histamine release (lasts around 10 minutes)

Causes sedation and respiratory depressionSacchetti et al showed it increased ICU

admissions – odds ratio 3.0

Acute treatment – conclusionsAcute treatment – conclusions

1. Nitrates are first line therapy and should be given intravenously if the patient is sick

2. Ace inhibitors are beneficial in acute CHF

3. Diuretics should be used in moderation4. Morphine should be used with extreme

caution

Chronic TherapyChronic Therapy

1. Ace Inhibitors/ ARB’s2. Betablockers - 3. Spironolactone4. Diuretics5. Digoxin

Ace inhibitorsAce inhibitors

Considered first line therapy for CHF. Recommended for all stages of CHF Absolute mortality reduction is around 15% at one

year for class III/IV patients with a NTT of 6 (relative risk reduction is 30 – 35%)

The effect on mortality was dose related and the higher the dose till the target range was reached ;the lower the mortality

Ace InhibitorsAce Inhibitors

These results were based on the CONSENSUS I/II, SOLVD, AND SAVE trials

Note the effect of ace inhibitors is reduced on patients who are on NSAIDS as well as ASA

Angiotensin Receptor Angiotensin Receptor Blockers (ARB’s)Blockers (ARB’s)

Were thought to be better because angiotensin II was still produced in patients on Ace inhibitors.

These drugs block the Angiotensin II receptor. Also they do not produce Bradykinens which Ace

inhibitors do. These Bradykinens lead to S/E such as cough and angioedema

ARB’sARB’s

Elite II – showed that there was no difference between ARB’s and Ace inhibitors. Mortality was 17.7% and 15.9% respectively

ARB’s were better tolerated They are recommended for patients who can’t

tolerate Ace inhibitors The current research is to see whether combined

therapy will reduce mortality

BetablockersBetablockers

Class I – nonselective- causes B1 and B2 blockade – propranolol

Class II - B1 selective – metoprolol, atenolol,

Class III- Nonselective with vasodilating properties – carvedilol,bucindol

Betablockers – Class IIIBetablockers – Class III

Class III- in addition to beta-blockade cause decreased norepinephrine release via B2 presynaptic inhibition

Also cause alpha 1 blockade leading to vasodilatation and afterload reduction

Main benefit is in patients who have a lot of symptoms of congestion and can’t tolerate other betablockers

Comet trial is comparing class II and class III betablockers

BetablockersBetablockers

Recommended for all patients with CHFShown to increase LVEF by 30%Decreases mortality by 4 – 5 % with NNT

of 23

SpironolactoneSpironolactone

RALES - showed 25 mg of spironolactone had a 30% relative risk reduction and an absolute risk reduction of 11% with a NNT of 9

Recommended for patients with class III/IV CHF

Note side effects were < 5% at this low dose

DiureticsDiuretics

Help control symptoms No effect on mortality

DigoxinDigoxin

No effect on mortalityReduced hospitalizations by 11% with a

NNT of 9 to prevent 1 hospitalization per year

Used as 4th line agent after ace inhibitors, beta blockers, spironolactone.

ConclusionsConclusions

CHF is a complicated disease that is evolving. It involves a lot of polypharmacy that needs gentle

titrating to control patient’s symptoms Ace inhibitors, beta blockers and diuretics are the

mainstay for chronic therapy Nitrates, Ace inhibitors and diuretics are the key

to acute therapy BNP will play a larger role in the assessment and

management of patients

QUESTIONS??QUESTIONS??