1. Congestive Heart Failure Arun Abbi M.D.

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

3. 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

4. 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%

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. Naturetic Peptides cont’d 3. C-type naturetic peptide – limited to the vascular endothelium and has limited effects on naturesis and vasodilatation

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

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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

19. Therapy Acute emergency therapy Chronic maintenance therapy

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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

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

29. 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

30. 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

31. 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

32. 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

33. Betablockers Class I – nonselective- causes B1 and B2 blockade – propranolol Class II - B1 selective – metoprolol, atenolol, Class III- Nonselective with vasodilating properties – carvedilol,bucindol

34. 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

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

36. 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

37. Diuretics Help control symptoms No effect on mortality

38. Digoxin Reduced hospitalizations by 11% with a NNT of 9 to prevent 1 hospitalization per year Used as 4 th line agent after ace inhibitors, beta blockers, spironolactone.

39. 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

40. QUESTIONS??