Congestive Heart Failure

Congestive Heart Failure Arun Abbi M.D.

Outline • 1. Classification and epidemiology • 2. Pathophysiology • 3. Diagnosis • 4. Treatment • 5. Conclusions

Classification • 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

Epidemiology • Congestive heart failure is the leading cause of admissions over the age of 65 • Affects 2% of the population • Incidence rises with age - affects 10% of those over 80 • Overall 5 year mortality is 50% • For Class IV – 1 year mortality is 35%

Pathophysiology • 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 Mechanisms • 1. Sympathetic system activation • 2. Activation of the Renin-Angiotensin Aldosterone system (RAAS) • 3. Increased naturetic peptides • 4. Increased Antidiuretic hormone • 5. Increased Endothelins

Sympathetic 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 Aldosterone System (RAAS) • Stimulation leads to increased Angiotensin II which leads to : • 1. Increased aldosterone • 2. Increased norepinephrine • 3.Inhibition of vagal tone

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

Antidiuretic Hormone • Is elevated in severe heart failure • Higher levels have been reported in patients on diuretics • Can lead to hyponatremia

Endothelins • Secreted by vascular endothelial cells • Potent vasoconstrictor peptide which leads to sodium retention • Increases in proportion to the hemodynamic severity of heart failure • Interest in developing endothelin receptor antagonists

Diagnosis • 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 • 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

BNP • 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

BNP • 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 • Acute emergency therapy • Chronic maintenance therapy

Acute Emergency Therapy • 1. Nitrates • 2. Diuretics • 3. Ace Inhibitors • 4. Morphine

Nitrates • Decreases preload and afterload (slightly) • Shown to be effective in reducing mortality and improving symptoms • Can be given sublingual, IV, or as a patch • Dose is 10mcg/min and can be titrated up every 3 – 5 minutes until desired effect. • Can cause hypotension

Nitrates • 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

Nitrates • 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

Diuretics • 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 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

Morphine • Causes venodilation through histamine release (lasts around 10 minutes) • Causes sedation and respiratory depression • Sacchetti et al showed it increased ICU admissions – odds ratio 3.0

Acute 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 moderation • 4. Morphine should be used with extreme caution

Chronic Therapy • 1. Ace Inhibitors/ ARB’s • 2. Betablockers - • 3. Spironolactone • 4. Diuretics • 5. Digoxin

Ace 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 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 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’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

Betablockers • 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 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

Betablockers • Recommended for all patients with CHF • Shown to increase LVEF by 30% • Decreases mortality by 4 – 5 % with NNT of 23

Spironolactone • 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

Diuretics • Help control symptoms • No effect on mortality

Digoxin • No effect on mortality • Reduced 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.

Conclusions • 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??

Congestive Heart Failure