Treatment of Heart Failure PDF

Learning Outcomes • To understand the strategies for treatment of chronic heart failure • To understand the strategies for treatment of acute heart failure • To recognise how the apparently paradoxical use of beta blockers is of benefit • To understand the mechanism of action and uses of drugs which...

Learning Outcomes • To understand the strategies for treatment of chronic heart failure • To understand the strategies for treatment of acute heart failure • To recognise how the apparently paradoxical use of beta blockers is of benefit • To understand the mechanism of action and uses of drugs which inhibit the renin-angiotensin-aldosterone system • To know the mechanism of action of digoxin and how it increases myocardial contractility • To know the mechanism of action and uses of inotropes Pharmacological treatment of Heart Failure Dr Alun Hughes ah200@ 2 Lecture Overview • Strategies for treatment • Points of intervention • Mechanisms of action Recap…. Signs and symptoms of heart failure 4 Left Ventricular Systolic Dysfunction (LVSD) = Heart failure with reduced ejection fraction (HFrEF) Aims of Treatment • Relieve symptoms • Improve exercise tolerance • Reduce incidence of acute exacerbations • Reduce mortality 5 Strategies for treatment • ↑ cardiac contrac lity • ↓ preload and/or a erload in order to ↓ cardiac work demand • By relaxing vascular smooth muscle • By reducing blood volume • Inhibit the Renin-Angiotensin-Aldosterone-System (RAAS) • Prevent inappropriate ↑ in heart rate • Mobilise the oedematous fluids Non Pharma : 1. Lifestyle factors – as per all CVD conditions, remember mental health factors 2. “Device therapy” • Pacing • Cardiac Resynchronisation Therapy • Implantable Cardiac Defibrillators • Coronary revascularisation • Heart transplant 7 Main Drugs Used in chronic Heart Failure (HFrEF) Loop diuretics • e.g furosemide, bumetanide ACE inhibitors • e.g. ramipril, Lisinopril Angiotensin II receptor blockers These approaches can prolong life in heart failure and counteract some of the symptoms of heart failure…But they don’t correct the underlying fault • e.g candesartan, losartan Beta-blockers • bisoprolol, carvedilol Aldosterone receptor antagonists • e.g. spironolactone ALSO… SGLT-2 inhibitors (more on those later) 8 • ACEI or ARB • Beta Blocker • Aldosterone antagonist Diuretics sometimes Prolong survival, improve outcomes 9 Overview of Treatment of Chronic Heart Failure Step 1 = “DAB” (D = Diuretic if fluid retention) A = ACE Inhibitor or ARB B = Beta-Blocker A&B shown to reduce mortality (i.e. prolong life!)and improve quality of life. Kidney function modifiers in HF - Increase excretion of sodium and water Loop diuretics (step 1) - furosemide, bumetanide Aldosterone receptor antagonists (step 2) - spironolactone PCT = Proximal convoluted tubule TAL = Thick ascending loop DT = Distal tubule CT = Collecting tubule Rang & Dale, Figure 28.4 (Page 350 7th Ed, page 358 8th Ed) Flexible loop diuretic regimes Use if clinical signs/symptoms of fluid overload/congestion Aim to achieve a “dry” weight using the lowest diuretic dose possible. Patient self-management with education: • daily weights – if varies in either direction, alter dose • Symptom review – breathlessness, peripheral oedema • Thirst level, dizziness, “washed out” GP – blood chemistry checks within a week of any dose change 12 Loop Diuretics (e.g. furosemide, bumetanide) common side-effects • Electrolyte disturbances –low K, Na, Mg, Ca • Hypotension • Renal impairment – measure eGFR • Hypovolaemia! • Nocturia if taken too late in day (troublesome) • Acute gout common with high doses 13 Renin Angiotensin System Inhibitors • • Use in HF with reduced EF of all NYHA classes Reduces morbidity/mortality Angiotensin converting enzyme inhibitors - ramipril, lisinopril Angiotensin AT1 receptor antagonists - candesartan, valsartan, (losartan) Using the ACEI and ARBs in HF • Reduce salt and water retention • Reduce vasoconstriction • Reduce vascular resistance • Reduce afterload • Improve tissue perfusion • Reduces ventricular remodelling and hypertrophy • Less effective in African or Caribbean ethnicity (try hydralazine+nitrate) • Start low dose, monitoring BP & blood chemistry and symptoms and uptitrating to maximum tolerated or target doses. HF – Heart failure 15 Renin-Angiotensin system inhibitors : Side effects/cautions Common to both • Dizziness • headache • Risk of hyperkalaemia (care with drug which also raise K+) • Renal impairment - can be reno-protective also • Avoid in bilateral renal artery stenosis • teratogenic Angiotensin converting enzyme (ACE) inhibitors • Persistent dry cough, tiredness, rare but serious – angioedema Angiotensin AT1 receptor antagonists (ARBs) • back/leg pain 16 Why Use Beta-Blockers in HF? ?Bad news - may slow HR, which could decrease CO… Good news • allows ventricle to fill more completely during diastole • Some Beta-blockers (e.g. carvedilol) cause vasodilation through blockage of alpha-receptors,  ↓ afterload • Reduce renin release by kidney 17 Beta-blockers for HF e.g. Carvedilol, Bisoprolol • Start if reduced ejection fraction but stable NYHA class II-IV • Start low, go slow • reduces mortality • Seek specialist advice if severe HF, current exacerbation of HF, heart block or bradycardia, persisting signs of fluid overload, low BP (SBP<90mmHg) - drug interactions – risk of bradycardia/AV block with: digoxin, amiodarone, verapamil, diltiazem 18 Beta-blockers side-effect examples • Bradycardia /Heart Block (contra-indicated) • Fatigue • Shortness of breath (Contra-indicated in Asthma) • Dizziness, cold peripheries, impotence/reduced libido, insomnia (more with older versions) 19 Step 2 : adding aldosterone antagonists (Mineralocorticoid receptor antagonists) • spironolactone, eplerenone • Add in if on ACEI or ARB + Beta-blocker + diuretic (“DAB”) and still symptoms • In NYHA class II-IV failure (effective in severe heart failure ) • low doses used • Reduces symptoms and mortality 20 Aldosterone Receptor Antagonists Common side effects • Hyperkalaemia • hyponatraemia • Nausea • Hypotension • gynaecomastia with spironolactone • renal impairment 21 Management of HF drug adverse effects • Flexible dosing for DABs, may need to up and down titrate. • Review BP – may be low but is patient symptomatic? • Bradycardia – if symptomatic may need to stop beta-blocker or review any other rate controlling drugs patient on . If HR<45 BPM – stop beta-blocker, call specialist 22 • ACEI or ARB • Beta Blocker • Aldosterone antagonist Diuretics sometimes Prolong survival, improve outcomes 23 Step 3 or 4 • Sacubitril – Valsartan combination Neprilysin ARB inhibitor • Ivabradine – specialist use only – reduces heart rate but not contractility, acts on sinus node. Use only if heart rate > 75 (in SR) 24 Other options to consider if concurrent…. Persistent sodium/water retention – Additional diuretics (e.g. thiazides like metolazone) Co-existing angina – Oral nitrates – Amlodipine (care!) Atrial fibrillation – Digoxin Digoxin – cardiac glycoside • option if other treatment strategies failing • shows no reduction in mortality rate • narrow therapeutic window Mechanisms of action: • (In AF : ↑ vagal efferent ac vity to the heart  ↓ SAN firing rate (↓ HR) and ↓ conduction velocity in the AV node) • In Heart Failure: Increases force of myocardial contraction – Inhibits Na/K ATP-ase pump, thus affecting Na/Ca exchanger, elevating intracellular calcium levels in Sarcoplasmic Reticulum then when Calcium released results in strengthened contractility • i.e. indirectly increases calcium levels and subsequent storage in the SR Digoxin inhibits Na/K ATPase pump, affecting the Na/Ca exchanger Increased force of myocardial contraction https://www.youtube.com/watch?v=T5O577a_ATc&t=2s 27 Digoxin sideeffects/toxicity: • • • • GI upset dizziness Conduction abnormalities Blurred or yellow vision Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors • e.g. Dapagliflozin • Normally used in treatment of diabetes • BUT decreases risk of further CVS mortality or likelihood of hospitalisation • NICE recommend for treating symptomatic CHF with rEF in adults as an odd-on to optimise standard care, i.e. • In patients on ACEi/ARB plus Beta Blockers (and MRAs if tolerated) • In patients on sacubitril/valsartan plus Beta Blockers (and MRAs if tolerated) 29 Treatment of Acute (decompensated) Heart Failure Sudden worsening of signs and symptoms of heart failure as a result of severe congestion of multiple organs. Increased dyspnoea, oedema Causes: MI, infection, anaemia, thyroid dysfunction, arrhythmia, uncontrolled hypertension, poor concordance Aims: • Normalise ventricular filling pressures • Restore adequate tissue perfusion 30 Overview of Treatment of Acute Heart Failure First Line Drug Treatments: IV loop diuretics • • • IV opiates (e.g. morphine) • • • • • Reduce anxiety Vasodilates, reducing preload Reduces sympathetic drive Not routinely offered IV nitrates (Glyceryl trinitrate “GTN”) • • • • • Cause venodilation and diuresis Reduces pre-load Reduce preload and afterload vasodilates Oxygen maintains O2 sats (Positioning – keep patient upright) L - loop M - morphine N -nitrates O - oxygen P - positioning Second line - Increasing contractility By use of inotropic agents (examples later) ↑ contrac lity will ↑ stroke volume, which ↑ Cardiac output (CO) so ↑ clearance of pooled blood in the ventricles As CO increases, baroreceptors sense change in MABP and ↓ sympathe c drive and so ↓ HR and ↓ TPR 32 Frank-Starling in Systolic Dysfunction Lilly, figure 9.3 Acute HF - Second line drug treatments: Intensive care units, Coronary Care Units only! Inotropes - beta-agonists - increase myocardial contractility – Dobutamine (beta 1&2) - in patients with cardiogenic shock to maintain blood pressure – Dopamine (DA > Beta > alpha) - Increases renal perfusion at low doses, can increase BP at high doses – Isoprenaline – in bradycardia/heart block emergencies - Adrenaline (beta>alpha) Vasopressors – Noradrenaline (alpha>beta) – cause vasoconstriction, raise BP, used in severe septic shock Main points of pharmacological intervention Learning Outcomes • To understand the strategies for treatment of chronic heart failure • To understand the strategies for treatment of acute heart failure • To recognise how the apparently paradoxical use of beta blockers is of benefit • To understand the mechanism of action and uses of drugs which inhibit the reninangiotensin-aldosterone system • To know the mechanism of action of digoxin and how it increases myocardial contractility • To know the mechanism of action and uses of inotropes