1. LIAM HEALY Cardiac Failure – pathophysiology and treatment

2. Cardiac failure – learning objectives Define, in one sentence, the term myocardial failure. List the signs and symptoms most commonly associated with chronic congestive heart failure. Give reasons for these. Summarise the neurohumoral mechanisms activated in congestive heart failure, and explain why these may be detrimental to the condition.

3. Symptoms of heart failure Exertional dyspnoea - pulmonary fluid and low o2 Orthopnoea (get breathless lying flat) – pulmonary fluid and low o2 Paroxysmal nocturnal dyspnoea (wake up short of breath – relieved by getting up) – low o2 Fatigue - lack of o2

4. Signs

5. Left Sided Cardiac Failure Less blood is pumped in the left ventricle. This means venous back pressure increases in the pulmonary circulation. This can cause fluid to enter the interstitium and alveoli of the lung. What symptoms will this cause? Dyspnoea and orthopnoea

6. Right Sided Cardiac Failure Less blood is pumped in the right ventricle. This means venous back-pressure increases in the systemic circulation (the vena cava). This causes hepatomegaly, engorged jugular veins, ascites, dependent oedema (e.g. legs swell after day standing up).

7. Congestive cardiac failure Left sided failure causing back pressure in the pulmonary system can then cause less blood to be pumped in the right ventricle, causing right sided cardiac failure. This is congestive cardiac failure

8. Cardiac failure - pathophysiology Cardiac failure is where cardiac output is inadequate to provide circulation for the body’s requirements. When this happens, there are several physiological compensatory responses that are supposed to maintain cardiac output and peripheral perfusion. These physiological mechanism eventually become maladaptive and pathological.

9. Pathophysiology - Mechanisms involved Venous return (preload), Outflow resistance (afterload), Myocardial contractility (inotropy) Salt and water retention. This eventually causes ventricular dilation

10. Venous return – (preload) physiology Starling’s Law – if cardiac muscle is stretched, it will contract harder. This means extra blood can enter the ventricle and be pumped out to increase cardiac output.

11. Venous return (preload) – patho-physiology 1 As heart failure gets worse, it can only be compensated by large increase in venous pressure. This contributes to dyspnoea by causing accumulation of interstitial and alveolar fluid in the lung. It also contributes to hepatic enlargement, ascites and oedema due to increased systemic venous pressure.

12. Venous return (preload) – patho-physiology 2

13. Outflow resistance (afterload) Physiology - There is vasoconstriction to maintain the perfusion of tissues. Pathophysiology - There is more pressure for the heart to pump against. This causes cardiac output to be decreased.

14. Myocardial contractility (inotropy) Physiology – myocytes contract harder and pump more blood, increasing cardiac output. Pathophysiology – Doesn’t really have a pathophysiology. However, it is mediated by the sympathetic nervous system which does cause pathophysiology and it eventually plays a role in dilation of the ventricle.

15. Ventricular remodelling This is a change in the mass, shape or size of a ventricle. It is caused by an increase in preload, an increase in afterload or an MI. Physiology – Hypertrophy of myocytes allows inotrophy to be increased. Pathophysiology - Hypertrophy of the myocytes can cause the ventricle to be over-dilated and this causes dysfunction of the heart as a pump.

17. How is all this mediated? 1. Renin-Angiotensin- Aldosterone-System 2. Sympathetic nervous system

18. Sympathetic nervous system - physiology The SNS is supposed to increase cardiac output by: 1. Increasing speed and strength of the heart contractions (increasing inotropy) 2. Peripheral vaso-constriction (increasing afterload)

19. Renin-Angiotensin-Aldosterone System The RAA system is supposed to increase cardiac output by: 1. Increasing retention of sodium and water (increasing preload) 2. Peripheral vaso-constriction (increasing afterload)

20. Summary

21. Causes of heart failure 1. Ischaemic heart disease – 35-40% 2. Dilated Cardiomyopathy – 30-34% 3. Hypertension – 15-20% Other causes – undilated cardiomyopathy, valvular heart disease, congenital heart disease, alcohol and drugs (chemotherapy), anemia, Arrhythmias, pericardial disease, infections, right heart failure

22. Cardiac failure 2 – learning objectives Identify the goals of treatment. Describe briefly the rationale for the use in the treatment of congestive heart failure of: ACE inhibitors, diuretics (e.g. furosemide and spironolactone), Give named examples of drugs used to treat congestive heart failure, outlining their likely mechanisms of action. State simplistically the currently accepted mechanism of action of digoxin and state its key uses.

23. The goals of treatment Reduce cardiac workload Increase cardiac output Counteract maladaptation Relieve symptoms Prolong quality life – reduce hospitalization

24. Obesity – maintain good weight Large meals should be avoided. Salt restriction is necessary. Alcohol has a negative inotropic effect so should be avoided. Smoking – stop it. Management – lifestyle advice:

25. Pharmacological management: Loop Diuretics – for symptoms management Beta blockers AND ACE inhibitors

26. These should be given in symptomatic patients. They have not been proved to improve survival but they reduce symptoms. Loop Diuretics 1 Loop diuretics are the main diuretics used in treatment of heart failure. Example = Furosemide

27. Site of action: thick ascending Loop of Henle Inhibit Na + K + 2Cl - co-transporter  Normally reabsorbs ~ 25% of sodium Unwanted effects:  Ototoxicity  Hypovolaemia  Hypomagnesaemia  magnesium and calcium reabsorption in thick ascending limb dependent on sodium and chloride concentrations Loop Diuretics 2

28. These are B adrenoceptor antagonists. They prevent the SNS mediating the maladaptive response. These improve mortality and symptoms long term However, they can worsen symptoms initially. Start low and go slow. Example - Bisoprolol Beta Blockers

29. Beta Blockers 2 – adverse effects Decrease cardiac output (acutely)  Increase risk of decompensated heart failure Hypotension Bronchospasm Cold hands & feet  vasoconstriction

30. ANGIOTENSINOGEN ANGIOTENSIN I ANGIOTENSIN II RENIN AT-1 RECEPTORAT-2 RECEPTOR VASOCONSTRICTION ALDOSTERONE VASOPRESSIN (ADH) SYMPATHETIC MYOCARDIAL & VESSEL HYPERTROPHY A.C.E EFFERENT CONSTRICTION Na+ RETENTION ACE-inhibitors Inhibitor

31. Effects of ACE inhibitors Arteriovenous vasodilation. This decreases preload and afterload Increased renal, coronary and cerebral blood flow Diuresis and natriuresis Modify progression Example = Ramipril

32. Adverse effects of ACE-Is Hypotension  Particularly 1 st dose Hyperkalaemia Renal insufficiency Dry cough Contraindications Hyperkalaemia Renal artery stenosis Hypersensitivity (Pregnancy)

33. Beta blockers ACE inhibitors Loop diuretics

34. Extra pharmacological management Angiotensin Receptor blockers – these are used instead of ACE inhibitors if the patient cannot tolerate ACE-Is (e.g. if they get a dry cough) Example = Losartan Spironolactone – aldosterone receptor blocker. This is used for specialist management of cardiac failure. Digoxin – a cardiac glycoside. It is not proven to help mortality but can prevent symptoms. Vasodilators – nitrates, etc can be used but very specialised.

35. Other pharmacological therapeutics I’ve talked about management of Cardiac Failure but you need to know about use of drugs in: Hypertension, Hyperlipidaemia, Anti-platelet and anti-thrombosis therapy.

36. THANKS

37. Sources Kumar and Clark’s Clinical medicine