hendy.pptx enteresto role in congestive heart failure

Entresto role in congestive heart failure

1. Mohamed H endy 24-4-2024 Tanta University. Entresto,The essential intervention ®

2. Introduction Contents Symptoms of heart failure Clinical signs of heart failure Causes of HF Types of HF Disease Burden Clinical stability in HF patient

3. Heart failure is a syndrome 1 – a complex mix of different symptoms and causes Should not be considered a disease Inadequate circulation and congestion result in a number of symptoms As not all symptoms are present in all patients, heart failure is very difficult to diagnose 1 Many symptoms can be indicative of other conditions 1 e.g. dyspnea and edema are also present in respiratory diseases, such as COPD 2,3 No symptom or sign both sensitive and specific to chronic heart failure 4 Heart failure: General symptoms Dyspnea Edema Chronic lack of energy Difficulty sleeping at night due to breathing problems Swollen or lender abdomen with loss of appetite Cough with frothy sputum Increased urination at night Confusion and/or impaired memory

4. Clinical signs of heart failure (1) Certain clinical signs can be used to aid heart failure diagnosis: 1,4 Elevated jugular venous pressure Indicative of increased central venous pressure Marker for right heart failure Hepato-jugular reflex : Video A physician presses on the liver whilst observing the internal jugular vein If there is prolonged swelling or distension of this vein, it indicates increased pressure in the pulmonary artery Third heart sound : Video Heard during early diastole, when the blood rapidly enters the ventricles from the atria 13 Audible with heart failure due to reduced elasticity of the ventricles when filling with blood 13 Bad prognostic sign Laterally displaced apical heartbeat Left ventricular hypertrophy displaces the location of the apex of the heart 14,15

5. Cardiac murmur : Video Abnormal heart sounds Can be caused, for example, by mitral valve regurgitation 15 Basal crepitations : Video Associated with pulmonary edema 16 Sound caused by the forced opening of alveoli compressed by fluid build-up in the lungs Hepatomegaly Engorgement of the liver 5,17 Results from peripheral congestion, increasing pressure in the hepatic veins 5,17 Manifests as abdominal discomfort, abnormal liver function tests, and, in severe cases, jaundice and cirrhosis 5,17 Clinical signs of heart failure (2)

6. There are a number of possible causes of heart failure which are illnesses themselves If patients with these illnesses were identified sooner and treated appropriately, then the end stage of these illnesses might not result in the onset of heart failure 16 Causes of heart failure High blood pressure Lung problems Poor blood supply to lungs Lung disease, asthma, bronchitis, obstructed airways High blood pressure in lungs Anemia Kidney disease Diabetes Obesity Disordered breathing during sleep Thyroid disorders Side effects of medications Other medical conditions Infections Rheumatic fever Chagas disease Heart Failure Valve defects Rhythm disorders Heart muscle defects Other disorders of the heart Coronary heart disease Heart problems Failure to take preventive medications Diet (excessive salt or fluid intake) Alcohol or drug misuse Lifestyle

7. Heart muscle diseases Myocarditis Inflammation of the heart muscle Weakened heart muscle Dilated cardiomyopathy Enlarged ventricle Hypertrophic cardiomyopathy Thickened heart muscle

8. Heart pumps oxygen-rich blood: lungs  left atrium  left ventricle  rest of the body Left ventricle responsible for most of the heart's pumping power In heart failure, there are functional or structural abnormalities of heart muscle: e.g. the left side of the heart must work harder to pump the same amount of blood 1 Types of abnormality: 2 Heart failure with reduced ejection fraction (HF r EF) Heart failure with preserved ejection fraction ( HF p EF ) Clinically, heart failure may also result from disorders of the layers of the heart, heart valves, or great vessels, or from some metabolic abnormalities 3 Types of heart failure

9. The introduction of HFmrEF (HF with mildly- reduced ejection fraction)

10. Burden Heart Failure

11. H eart failure is considered as the ‘cancer of the heart ’ HF is a major and growing public health problem

12. 26 MILLION ADULTS WORLDWIDE ARE LIVING WITH HEART FAILURE AND THIS NUMBER IS EXPETED TO RISE 1,2 AGING POPULATION 2 INCREASING PREVALENCE OF RISK FACTORS 2 IMPROVED POST-MI SURVIVAL 2 A person at age 40 has a 1 in 5 lifetime risk of developing heart failure, and more than 1 million hospitalisations due to heart failure are reported annually in Europe. 1,4 1. Mozaffarian D, Benjamin EJ, Go AS, et al; for American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation. 2015;131(4):e29-e322. 2. Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart. 2007;93(9):1137-1146. 3. Velagaleti RS, Vasan R. Epidemiology of heart failure. In: Mann DL, ed. Heart Failure: A Companion to Braunwald's Heart Disease. 2nd ed. St Louis: Saunders; 2011. 4. Ponikowski P, Anker SD, AlHabib KF, et al. Heart failure: preventing disease and death worldwide. ESC Heart Failure. 2014;1(1):4-25. HF is a major and growing public health problem

13. Heart failure leads to frequent hospitalizations HF, heart failure Bui et al. Nat Rev Cardiol 2011;8:30–41; 2. Maggioni et al. Eur J Heart Fail 2013;15:808–17; 3. Ponikowski et al. ESC Heart Fail 2014;1:4-25 ; 4. Kociol et al. Am Heart J 2013;165:987–94; 5. Cleland et al. Eur Heart J 2003;24:442–63 HF is one of the most common causes of hospitalization for patients aged >65 years in developed countries 1 Nearly 44% of all HF patients are readmitted for any cause within 1 year after discharge 2 Length of stay for HF hospitalization ranges between 5–10 days 3 In the USA, 30-day re-admission rates are >25% 4 In Europe, re-admission rates are ~24% at 12 weeks 5

14. 14 1. Cowie et al. ESC Heart Failure 2014;1:110–45; 2. Healthcare Cost and Utilization Project 2009. Available at: http://www.hcup-us.ahrq.gov/reports/factsandfigures/2009/pdfs/FF_2009_exhibit2 ; 3. Maggioni AP, Dahlström U, Filippatos G et al. EURObservational Research Programme : regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail 2013;15:808–17 4. Lee DS, Austin PC, Stukel TA et al. "Dose-dependent" impact of recurrent cardiac events on mortality in patients with heart failure. Am J Med 2009;122:162–95; 5. Ahmed. A propensity matched study of New York Heart Association class and natural history end points in heart failure. Am J Cardiol 2007;99:549–53 HF=heart failure; NYHA=New York Heart Association; USA=United States of America Patients with HF are at high risk of repeated hospitalizations Admission Discharge Re-admission All patients with HF are at increased risk of frequent, repeated hospitalizations 1,3,4 In developed countries , HF is the primary cause of hospitalization in patients aged >65 years 1,2 1–3% of all hospital admissions in Europe and the USA are for HF 1 ~44% of patients will be rehospitalized at least once 3 1 year Hospitalization rates for HF are comparable for patients with mild (NYHA class I/II; 66%) and moderate/ severe (NYHA class III/IV; 71%) HF 5

15. 15 1. Cook C, Cole G, Asaria P et al. The annual global economic burden of heart failure. Int J Cardiol 2014;171:368–76 2. Dickstein K, Cohen-Solal A, Filippatos G et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008;29:2388–442 ; 3. Mozaffarian D, Benjamin EJ, Go AS et al. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation 2015;131:e29–322; 4. Heidenreich PA, Albert NM, Allen LA et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail 2013;6:606–19 *Based on the estimated cost of HF in the USA in 2010. The remaining costs for HF are attributed to nursing home, physicians/other professionals, drugs/other (home health care, medical durables), and lost productivity (morbidity and mortality). ‡ Direct costs include expenditure on hospital services, medications, physician costs, primary healthcare costs and follow-up. § Indirect costs include expenditure in terms of lost productivity resulting from morbidity and mortality, sickness benefit and welfare support HF=heart failure HF imposes a significant economic burden on the healthcare system ~ 2 % of the total healthcare budget in many countries is spent on the treatment of HF 1 ~127% by 2030 Due to an aging population, the total cost of HF in the USA alone is expected to increase $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ $ In 2012, the overall worldwide cost of HF was ~ $108 billion 1 $65 billion direct costs ‡1 $43 billion indirect costs §1 $ $ 2012 2030 HF has a significant economic burden due to the direct and indirect costs associated with disease progression 1 3,4 70 % of the cost of HF is due to hospitalizations 2 $ $ $ $ $ $ $ $ $ $

16. HF can severely affect patients’ social capacity and emotional health 1,2 Patients with HF often suffer from fear, anxiety or depression, feel a loss of self-control and have difficulty performing daily activities 3 16 HF has a detrimental effect on quality of life 1. Calvert MJ1, Freemantle N, Cleland JG t et al. The impact of chronic heart failure on health-related quality of life data acquired in the baseline phase of the CARE-HF study. Eur J Heart Fail 2005;7:243–51; 2. Moser DK, Dracup K, Evangelista LS et al. Comparison of prevalence of symptoms of depression, anxiety, and hostility in elderly patients with heart failure, myocardial infarction, and a coronary artery bypass graft. Heart Lung 2010;39:378–85; 3. Cowie et al. ESC Heart Failure 2014;1:110–45; 4. Gwaltney et al. Presented at the American Heart Association Quality of Care and Outcomes Research in Cardiovascular Disease and Stroke 2010 Scientific Sessions, Washington, D.C., May 19–21, 2010 HF=heart failure

17. Clinical stability in heart failure patient !

18. HF has a progressive nature.... patients cannot be perceived as ‘stable’ 1. Adapted from Gheorghiade et al. Am J Cardiol 2005;96:11G–17G; 2. Ahmed et al. Am Heart J 2006;151:444–50; 3. Gheorghiade and Pang. J Am Coll Cardiol 2009;53:557–73; 4. Holland et al. J Card Fail 2010;16:150–6; 5. Muntwyler et al. Eur Heart J 2002;23:1861–6 Frequency of decompensation and risk of mortality increase, 1–5 with acute events and sudden death occurring at any time Mortality Cardiac function and Quality of life Decompensation/ hospitalization Chronic decline 1 Disease progression

19. …of HF Patients are readmitted at least once for any cause during the 1-year follow-up Approximately half of all re-hospitalizations occurring in a year, happen within the first 30 days of discharge The 1-month readmission rate of for all-cause rehospitalization is approximately… Risk of rehospitalization for HF patients is disproportionately high in the first 30 days 44 % 25 % Maggioni AP, Dahlström U, Filippatos G et al. EURObservational Research Programme : regional differences and 1-year follow-up results of the Heart Failure Pilot Survey (ESC-HF Pilot). Eur J Heart Fail 2013;15:808–17

20. The Conundrum of Heart Failure HF is an illness that consumes substantial healthcare resources, inflicts considerable morbidity and mortality, and greatly affects quality of life Mortality ~50 DIE WITHIN 5 YEARS OF DIAGNOSIS 2 Hospitalization In developed countries, HF is the primary cause of hospitalization in patients aged >65 years 1,2 44 % of patients will be re-hospitalized at least once Quality of Life Economic 76% of patients struggle to perform their daily activities 63% of patients reported symptoms that are consistent with depression HF has a significant economic burden due to the direct and indirect costs 70% of the cost of HF is due to hospitalizations

21. 21 Goals of HF management There are three major goals of treatment for patients with HFrEF: 1 1. Reduce mortality 2. Prevent recurrent hospitalizations due to worsening HF 3. Improve clinical status, functional capacity, and quality of life Optimization of GDMT contributes to achieving these goals GDMT, guideline-directed medical therapy; HF, heart failure; HFrEF, heart failure with reduced ejection fraction. Reference: 1. McDonagh TA et al. Eur Heart J 2021; 42: 3599-3726.

22. Levin et al. N Engl J Med 1998;339:321–8. Nathisuwan & Talbert. Pharmacotherapy 2002;22:27–42 . Kemp & Conte. Cardiovascular Pathology 2012;365–71 . Schrier & Abraham. N Engl J Med 1999;341:577–85 Target neuroendocrine activation and its sequelae HF SYMPTOMS & PROGRESSION Sympathetic nervous system Epinephrine Norepinephrine α 1 , β 1 , β 2 receptors Vasoconstriction RAAS activity Vasopressin Heart rate Contractility Renin-angiotensin- aldosterone system Vasoconstriction Blood pressure Sympathetic tone Aldosterone Hypertrophy Fibrosis Ang II AT 1 R Vasodilation Blood pressure Sympathetic tone Natriuresis/diuresis Vasopressin Aldosterone Fibrosis Hypertrophy NPRs NPs Natriuretic peptide system Decline in systolic function leads to activation of three major neurohormonal systems Neprilysin degrades natriuretic peptides and other substrates, including Ang II and vasoactive peptides relevant for cardiovascular physiology 10 Further Heart Failure

23. NEP inhibitors: natriuretic and other vasoactive peptides enhancement Evolution of pharmacologic approaches in HF: Neprilysin inhibition as a new therapeutic strategy in patients with HF SNS RAAS Vasoconstriction Blood pressure Sympathetic tone Aldosterone Hypertrophy Fibrosis Ang II AT 1 R HF SYMPTOMS & PROGRESSION INACTIVE FRAGMENTS NP system Vasodilation Blood pressure Sympathetic tone Natriuresis/diuresis Vasopressin Aldosterone Fibrosis Hypertrophy NPRs NPs Epinephrine Norepinephrine α 1 , β 1 , β 2 receptors Vasoconstriction RAAS activity Vasopressin Heart rate Contractility Neprilysin inhibitors RAAS inhibitors (ACEI, ARB, MRA) β -blockers 1. McMurray et al. Eur J Heart Fail. 2013;15:1062–73; Figure references: Levin et al. N Engl J Med 1998;339:321–8; Nathisuwan & Talbert. Pharmacotherapy 2002;22:27–42; Kemp & Conte. Cardiovascular Pathology 2012;365–371; Schrier & Abraham N Engl J Med 2009;341:577–85 ACEI=angiotensin-converting-enzyme inhibitor; Ang=angiotensin; ARB=angiotensin receptor blocker; AT1 = angiotensin II type 1; HF=heart failure; MRA=mineralocorticoid receptor antagonist; NEP= neprilysin ; NP=natriuretic peptide; NPRs=natriuretic peptide receptors; RAAS=renin-angiotensin-aldosterone system; SNS=sympathetic nervous system

24. Simultaneous inhibition of neprilysin and suppression of the RAAS with Entresto ® has complementary effects 24 HFrEF Symptoms & Progression Sympathetic Nervous System Renin-Angiotensin-Aldosterone system Natriuretic peptide system Vasodilatation Blood pressure Sympathetic tone Natriuresis / Diuresis Vasopressin Aldosterone Fibrosis Hypertrophy Vasoconstriction RAAS-activity Vasopressin Heart rate Contractilit y Vasoconstriction Blood pressure Sympathetic tone Aldosterone Hypertrophy Fibrosis NPRs NPs Epinephrine Norepinephrine α 1 , β 1 , β 2 receptors Ang II AT 1 R Inactive fragment Neprilysin AT 1 R=angiotensin II type 1 receptor; RAAS=Renin-Angiotensin-Aldosterone-System; NPRs=natriuretic peptide receptors; NP=natriuretic peptide; SNS=sympathetic nervous system 1. Levin et al. N Engl J Med 1998;339:321–8; 2. McMurray et al. Eur J Heart Fail 2013;15:1062–73; 3. Nathisuwan and Talbert. Pharmacotherapy 2002;22:27–42; 4. Kemp and Conte. Cardiovasc Pathol 2012;21:365–71; 5. Schrier and Abraham. N Engl J Med 1999;341:577–85 Valsartan Sacubitril Sacubitril/valsartan

25. Special patient population