Management of heart failure 23.02.24.pptx

this is a powerpoint describing the latest advances in management of heart failure.

1. Dr.c.k . mulwa Management of heart failure

2. Objectives Understand basics of heart failure pathophysiology. Understand the pillars of heart failure mx based on guideline directed medical therapy(GDMT) for the treatment of heart failure.

3. Heart Failure: definition A progressive disorder in which the heart is unable to pump sufficient blood to meet the needs of the body (decreased cardiac output). Ejection fraction , A measure of how much blood is pumped out of the ventricles with each contraction. Normal: 55-70% Heart failure with reduced ejection fraction- clinical syndrome typically with signs and symptoms and an EF < 40% Heart failure with preserved ejection fraction- Clinical syndrome with signs and symptoms of heart failure and EF of >40%

4. Pathophysiology: Causes of heart failure Left ventricular systolic dysfunction Coronary artery disease Idiopathic dilated cardiomyopathy (DCM) Vulvular heart disease Hypertension Toxin induced cardiomyopathies ( e.g., doxorubicin, herceptin , alcohol) Congenital heart disease 

5. Pathophysiology ↑ neurohormonal activation (SNS and RAAS) ↑ fluid retention ↑ vasoconstriction Diuretics Digoxin Vasodilators RAAS inhibitors BB SGLT2i Imbalance between physiologic demands and cardiac output BB, β-blockers; RAAS, renin-angiotensin-aldosterone system; SGLT2i, sodium glucose co-transporter 2 inhibitors; SNS, sympathetic nervous system. Parker RB, et al. Chronic heart failure. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. McGraw Hill; 2017.

6. Pathophysiology: Counter-regulatory changes in HF In LV systolic dysfunction, the body activates several neurohormonal pathways to increase circulating blood volume. The sympathetic nervous system Increases heart rate and contractility, Causes arteriolar vasoconstriction in nonessential vascular beds, Stimulates secretion of renin from the juxtaglomerular apparatus of the kidney. Unfortunately, catecholamines aggravate ischemia, potentiate arrhythmias and promote cardiac remodelling

7. Pathophysiology: Counter-regulatory changes in HF Stimulation of the renin-angiotensin system: Results from increased sympathetic stimulation and decreased renal perfusion Results in further arteriolar vasoconstriction and release of aldosterone. An increased aldosterone level, in turn, leads to sodium and water retention

8. Pathophysiology: Counter-regulatory changes in HF Baroreceptor stimuli Lead to vasopressin (antidiuretic hormone, ADH,) release from the hypothalamus, causing reabsorption of water in the renal collecting duct. NB: Although these neurohormonal pathways initially are compensatory and beneficial, eventually they are deleterious.

9. Pathophysiology :Myocardial changes in heart failure In a normal heart, a compensatory increase in performance occurs as the stretched myocardium responds through increased elastic recoil . In the failing heart, this property of cardiac muscle recoiling under stretch is diminished and therefore the heart dilates abnormally to accommodate the increased ventricular load. Failure of the heart to handle the increasing ventricular load leads to pulmonary and venous congestion . At the same time, the increased tension on the ventricular wall in heart failure raises the myocardial oxygen requirements thus predisposing the patient to myocardial ischaemia .

10. Pathophysiology: Myocardial changes in heart failure The failing heart may show cardiac enlargement due to dilation but this is reversible with treatment. An irreversible increase in cardiac muscle mass (cardiac hypertrophy) may occur with progression of heart failure and is usually a consequence of long standing hypertension . While hypertrophy may initially alleviate heart failure, the increased muscle mass results in increased workload and oxygen consumption.

11. Pathophysiology: Counter-regulatory changes in HF Other effects: natriuretic peptides Natriuretic peptides are hormones released by secretory granules in cardiac myocytes in response to myocardial stretching. They have a beneficial influence in heart failure, including systemic and pulmonary vasodilation, possible enhancement of sodium and water excretion, and suppression of other neurohormones .

12. The Vicious Cycle of Congestive Heart Failure Decreased Blood Pressure and Decreased Renal perfusion Stimulates the Release of renin, Which allows conversion of Angiotensin to Angiotensin II . Angiotensin II stimulates Aldosterone secretion which causes retention of Na+ and Water, increasing filling pressure LV Dysfunction causes Decreased cardiac output

13. Homeostatic Responses to Impaired Cardiac Performance Response Short-Term Effects* Long Term Effects Salt and water retention Augments preload to increase cardiac output Pulmonary congestion and peripheral edema Vasoconstriction Maintains blood pressure for perfusion of vital organs Exacerbates pump dysfunction (increased cardiac afterload and energy expenditure) Sympathetic stimulation Increases heart rate and ejection (increased output) Increases energy expenditure and causes arrhythmias Cardiac hypertrophy Adaptive: increased sarcomere number with increased cardiac output Maladaptive: accelerated cell death, arrhythmias

14. Symptoms of Heart Failure F Fatigue A Activities limited C Chest congestion E Edema or ankle swelling S Shortness of breath

15. NYHA Classification of Heart Failure NYHA Class Description I No symptoms with ordinary physical activity such as walking or climbing stairs II Slight limitation with dyspnoea on moderate to severe exertion such as climbing stairs or walking uphill III Marked limitation of activity and less than ordinary activity causes dyspnoea e.g. restricting walking distance and limiting climbing to one flight of stairs IV Severe disability, dyspnoea at rest and the patient is unable to carry on physical activity without discomfort

16. Treatment of Heart Failure Correction of systemic factors Thyroid dysfunction Infections Uncontrolled diabetes Hypertension Lifestyle modifications Dietary sodium restriction to 2g/day and fluid intake restriction to 2L/day To lessen congestion and decrease the need for diuretics Alcohol cessation Smoking cessation Others: daily weight monitoring, light aerobic exercise. Pharmacological management

17. Pharmacological management of HF Cardiac performance is determined by: Preload, Afterload, Myocardial contractility Heart rate. Treatment targets these aspects, often by blocking the counter-regulatory mechanisms.

18. Pharmacological management of HF Cardiac function target Description Effects of drugs Cardiac preload Cardiac preload is increased by salt and water retention, capacitance vessel tone and sympathetic nervous system activation. Drugs can reduce blood volume (diuretics) and reduce capacitance vessel tone (vasodilators). Afterload Afterload is determined by the systemic vascular resistance and by aortic stiffness. Drugs that relax arterial smooth muscle reduce cardiac afterload. Myocardial contractility Positive inotropes (i.e. drugs that increase the force of contraction of the heart) can improve cardiac performance temporarily by increasing contractility, but at the expense of increased oxygen consumption and risk of dysrhythmia. Heart rate Cardiac function deteriorates as heart rate increases beyond an optimum, due to insufficient time for filling during diastole. Heart rate can be slowed by negative chronotropes (i.e. drugs that slow the heart).

19. Pharmacological Mx: ACE inhibitor e.g. Enalapril ARB e.g. Losartan, Valsartan Aldosterone antagonists, e.g. Eplenonone , Spirilonolactone Angiotensin ii receptor- neprilysin inhibitors ( ARNI)- Sacubitril/Valsartan Beta blockers- Bisoprolol , Carvedilol Cardiac glycosides- Digoxin Direct vasodilators- Hydralazine

20. Pharmacological Mx: Loop diuretics e.g. Furosemide, Torsemide Thiazide diuretics e.g HCTZ Nitrates- e.g. Isosorbide mononitrate Vasopresssin antagonists e.g. Tolvaptan ‘I’ channel blockers- e.g. Ivabradine Sympathomimetics e.g. Noradrenaline, dobutamine Phosphodiesterase inhihibitors e.g. Milrinone SGLT2i- e.g. Empagliflozin CCBs- e.g. Amlodipine

21. Guideline directed medical therapy(GDMT) for the treatment of heart failure. Newest guidelines on mx of HFrEF indicate thar patients should be started on quadriple therapy with the 4 pillar drugs at once at low doses then doses titrated up There are 4 pillars of GDMT tx of HFrEF . Beta Blockers Mineralocorticoid receptor antagonists Angiotensin 11 receptor neprilysin inhibitors/ ACEis Sodium Glucose cotransporter 2 inhibitors

22. Titrate to target dose based on patient tolerance and add additional therapy as needed. ARNI or ACEi/ARB Consider additional pharmacological therapies Diagnosis of HF with EF <40% GDMT African American NYHA III-IV  Hydral/nitrates Beta SGLT2i MRA Blocker Diuretics (PRN) NYHA I- III EF ≤35% >1 year expected survival  ICD NYHA II-III (IV if ambulatory), with NSR and QRS <150msec  CRT- D 2022 American Heart Association/American College of Cardiology HF Guidelines Heidenreich PA, et al. Circulation . 2022;145(18):e895-e1032.

23. Beta blocker therapy Moa; Act by combating the sympathetic overactivity which occurs in response to the failing heart They also minimize the abnormal structural and physiological changes that occur in the cardiac muscle in response to the overactivity. Contraindications/cautions Heart rate <60 bpm ( bradycardia ) COPD, asthma Heart conduction abnormalities: 2 nd or 3 rd degree block Diabetes

24. Beta- Blocker Clinical Pearls Possibly most beneficial class Assess fluid status Avoid non selective BB in asthma Reduces all- cause mortality by >30% Benefit within 30 days Do not start when patient is “wet” Decreases cardiac output (negative inotrope/ chronotrope ) optimize loo p diuretic s PRN Avoid abrupt discontinuation Target dose / HR Start low and titrate slow HR, heart rate. Greene SJ, et al. J Card Fail . 2022;28(3):370- 384; Heidenreich PA, et al. Circulation . 2022;145(18):e895- e1032; Fox K, et al. Lancet. 2008;372(9641 ) :817- 821.

25. Dosing and Details Carvedilol ≤85 kg: 25 mg twice a day >85 kg: 50 mg twice a day With food Metoprolol succinate 200 mg daily Becomes less selective at higher doses Bisoprolol 10 mg daily Heidenreich PA, et al. Circulation . 2022;145(18):e895-e1032. Target doses

26. ACE inhibitors MOA: Decrease the afterload on the heart by reducing formation of angiotensin II which is a potent vasoconstrictor on the arterial system. They also reduce venous congestion and preload by inhibiting the release of aldosterone from the adrenal cortex. Begin therapy low and titrate up as possible: Enalapril – 2.5 mg po BID Captopril – 6.25 mg po TID Lisinopril – 5 mg po QDaily If the patient cannot tolerate, switch to ARB

27. Angiotensin Receptor Neprilysin Inhibitor( ARNI) Valsartan/ Sacubitril MOA: combines the action of Valsartan ( ARB) and sacubitril Valsartan Angiotensin ii receptor blocker that decreases BP by blocking vasoconstriction and aldosterone- secreting effects of angiotensin ii reducing salt & water retention Sacubitril Prevents degradation of endogenous natriuretic and vasodilator peptides which results to vasodilation and diuresis When combined the 2 reduce the strain of the failing heart

28. NYHA class 2- 3 HFrEF Contraindicated in history of angioedema / Cough on ACEi ARNI should not be administered within 36 hours of the last dose of an ACEi due to risk of angioedema ARNIs lower BP more than ACEi or ARB Patients on ACEi or ARB should be transitioned to ARNI Start sacubitril/valsartan 49 mg/51 mg twice a day, double in 2- 4 weeks Target 97/103 mg Target doses reduce Mortality and hospitilization as demonstrated in the paradigm- HF study . Sacubitril/Valsartan Clinical Pearls

29. Angioedema Risk Heidenreich PA, et al. Circulation . 2022;145(18):e895-e1032. Inactive metabolites Inactive metabolites Bradykinin X A CE N e X pril y sin Sacubitril ACEi Need 36- hour washout period from ACEi to prevent angioedema

30. Potassium-sparing diuretics Spironolactone, eplerenone Antagonize the effects of aldosterone at the late distal tubule and cortical collecting tubule. They induce diuresis improve survival in HF Dosing for both spironolactone and eplerenone: start at 25 mg daily and may increase to 50 mg after a month Eplerenone, less endocrine abnormlities such as gynacomastacia , bph

31. Contraindications and precautions These agents can cause severe, even fatal hyperkalemia in susceptible patients. Oral K+ administration should be discontinued if aldosterone antagonists are administered. Patients with chronic renal insufficiency are especially vulnerable and should rarely be treated with aldosterone antagonists. Concomitant use of other agents that blunt the renin-angiotensin system ( β -blockers or ACE inhibitors) increases the likelihood of hyperkalemia . Patients with liver disease may have impaired metabolism of triamterene and spironolactone, and dosing must be carefully adjusted. Strong CYP3A4 inhibitors ( eg , ketoconazole, itraconazole) can markedly increase blood levels of eplerenone.

32. Sodium Glucose Co- Transporter 2 Inhibitor Empagliflozin or Dapagliflozin NYHA class 2- 4 10 mg initial and target dose DAPA- HF and EMPEROR- Reduced trials: cardiovascular (CV) death ↓ ≈25% and HF hospitalization by ≈30% Best evidence in mildly reduced, improved, and preserved HF Docherty KF, et al. JACC Heart Fail . 2020;8(10):800- 810; Heidenreich PA, et al. Circulation . 2022;145(18):e895- e1032; Inspra. Prescribing information. Pfizer; 2008.

33. Inappropriate Medications in HF Non- dihydropyridine calcium channel blocker (verapamil, diltiazem; negative inotrope) Stimulants (decongestants, amphetamines; Increase oxygen demand ) Nonsteroidal anti- inflammatory drugs, corticosteroids (fluid retention, increase vascular resistance) α1 blocker (RAAS stimulation, increase HR) DPP4 (Dipeptidyl peptidase- 4) (mechanism unknown, can increase risk of angioedema with ACEi/ARNI) Ci Thiazolidinedione (fluid retention) El Hadidi S, et al. Eur Heart J Cardiovasc Pharmacother . 2022;8(2):187- 210; Heidenreich PA, et al. Circulation . 2022;145(18):e895-e1032.

34. Take home points HF is often suboptimally managed and continues to be associated with high hospitalization rates and mortality GDMT for HFrEF is based on the “4 pillars”: ARNI, BBs, MRA, and SGLT2i Medications should be initiated and up- titrated with the aim of achieving target doses in a reasonably short time period Look out for drugs that worsen HF

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