MGEM2019 Causes and Consequences of Heart Failure 22-23.pptx

Causes and Consequences of Heart Failure Nairouz Alathram- MGEM2019 Learning objectives • To define the term heart failure • To list conditions that can lead to heart failure • To describe the pathophysiology of heart failure and symptoms/signs in patients • To describe, in outline terms, the trea...

Causes and Consequences of Heart Failure Nairouz Alathram- MGEM2019 Learning objectives • To define the term heart failure • To list conditions that can lead to heart failure • To describe the pathophysiology of heart failure and symptoms/signs in patients • To describe, in outline terms, the treatment options for heart failure Content Introduction: Overview cardiovascular system Terms and Definition: Preload Causes symptoms of Heart failure Treatment Recap Quick Reminder ! What is preload in the heart? Afterload? Workload? How can they be related to heart failure! Introduction • Heart Failure: a heart that cannot keep up with its workload. The body may not get the oxygen it needs. • A heterogeneous syndrome in which an abnormality of cardiac function is responsible for the inability of the heart to pump blood at an output sufficient to meet the requirements of metabolizing tissues, or to do so only at abnormally elevated diastolic pressures or volumes (Goldman and Ausiello (Eds.) Cecil Textbook of Medicine 22nd Ed. 2004, Saunders, Philadelphia) Impact! • 920,000 people in the UK today have been diagnosed with heart failure. • 60,000 new cases every year. • In 2019 there were 530,841 deaths registered in England and Wales. • 4,000 deaths in the UK each year Determinants of LV function Inotropy Afterload Preload Stroke Volume • Synergistic LV Contraction • Wall Integrity • Valvular Competence Heart Rate Cardiac Output Terms and Definition Diastolic: relating to the phase of the heartbeat when the heart muscle relaxes and allows the chambers to fill with blood. Diastolic heart failure: is a condition in which your heart's main pumping chamber (left ventricle) becomes stiff and unable to fill properly. Systolic: relating to the phase of the heartbeat when the heart muscle contracts and pumps blood from the chambers into the arteries. Systolic heart failure: also called heart failure with reduced ejection fraction, occurs when your left ventricle can't pump blood Workload tells you how hard your heart must pump to supply the body with the blood it needs. Cardiac oxygen demand is determined by workload, which is determined by cardiac output, which is determined by the heart rate and stroke volume and by the back pressure against the aortic valve (diastolic blood pressure) : (CO = HR x SV) Preload: Preload is defined as the stretch of myocardium or end-diastolic volume of the ventricles and most frequently refers to the volume in a ventricle. Afterload is defined as the force opposing fiber shortening during ventricular ejection. Causes of Heart Failure • Heart failure is always secondary to something else, for example: • Coronary artery disease • Hypertension • Cardiomyopathy • Valvular heart disease • Pericardial disease This is why it is not a diagnosis, but a syndrome Adaptive Mechanisms • Frank – Starling mechanism. • Ventricular remodelling (dilatation and hypertrophy) • Activation of the sympathetic nervous and reninangiotensin-aldosterone systems (neurohumoral) • Others - Cytokine activation; Arginine Vasopressin (ADH); endothelin systems  Frank-Starling Mechanism is the major intrinsic cardiac mechanism by which the heart can adapt, beat by beat, to varying amounts of returning venous blood  When cardiac muscle is stretched an extra amount (e.g. more blood entering the ventricle) the stretched muscle contracts with a greater force, so automatically pumping the extra blood out  So, if stretch on a normal myocyte increases, it augments contraction within its physiologic limits  This is the cardiac preload  The physiologic basis for this is found in the lengthtension and force-velocity relationships for cardiac myocytes Systolic Excursion Preload Diastolic Dimension Frank–Starling Mechanism Frank–Starling Mechanism in Heart Failure Frank–Starling Mechanism in Heart Failure Inotropy • Inotropy refers to the contractility of the ventricle • Cardiac muscle is unique in that in can alter its intrinsic inotropic state • Changes in inotropy alter the rate of force and pressure development by the ventricle, and therefore change the rate of ejection (and therefore stroke volume) • Cellular mechanisms responsible involve intracellular calcium flux and can be influenced by things such as exercise, adrenergic stimulation and other inotropic agents Quick Reminder! Factors can promote Calcium (+ve inotropic agent): A. Noradrenaline B. Thyroid hormones. Factors decrease Calcium viability: A. Ca++ blocker. B. Electrolyte imbalance. Afterload •Afterload is the “load” against which the heart must contract to eject blood • A major component of the afterload for the left ventricle is the aortic pressure, or the pressure the ventricle must overcome to eject blood • However, the haemodynamic method of assessing afterload is the Systemic Vascular Resistance or SVR (also known as TPR orTotal Peripheral Resistance) Quiz ! Which of the following associated with preload: a) Preload is the stretch that the blood places on the wall of the ventricles. b) It take place at the end-diastolic volume (EDV). c) Is directly related with amount of blood ejected (Frank-starling mechanism). d) All of the above. Ventricular Remodelling • In a proportion of patients, progressive remodelling can occur over months and years • An adaptive response has become a maladaptive process • Non-infarcted segments appear to elongate leading to progressive dilatation of the ventricle • This elongation is due to eccentric hypertrophy of the myocytes, myocyte slippage, collagen matrix reorganisation (increase) and, possibly, apoptosis • This presumably has initial short term benefits due to the Frank-Starling mechanism; but this is eventually insufficient to maintain cardiac output • The molecular mechanisms underlying this progressive remodelling are poorly understood but involve intrinsic and extrinsic (neurohumoral) factors Neurohumoral Activation • • • • • • Sympathetic Nervous system - NEURAL Renin-angiotensin-aldosterone axis Arginine vasopressin (ADH) Natriuretic peptides - HUMORAL Endothelin system Cytokines Potentially Advantageous Effects of SNS Activation • At rest, the normal LV requires no adrenergic support • When LV dysfunction is present – adrenergic support is triggered to enable: 1.Cardiac Stimulation – chronotropic and inotropic 2.Peripheral vasoconstriction 3.Activation of the renin-angiotensin system • These are essentially designed for “short-term” support of the circulation Deleterious Effects of SNS Activation in the Long-term • Beta receptors in heart become down-regulated with constant stimulation • In the peripheral circulation chronic arterial vasoconstriction increases myocardial workload and energy requirements : cardiac remodelling is adversely affected • Plasma norepinephrine levels are high in heart failure, and correlate with prognosis (the higher it is, the worse it is) Renin–Angiotensin–Aldosterone System • Activated later in the disease process, usually when clinical symptoms are present • Decreased renal perfusion and sympathetic nervous system activation are probably the main triggers for RAAS activation • We also now know that there is a tissue-level RAA system – this probably Main effect is sodium and water retention by the kidney with a consequent increase in extracellular fluid volume – in the plasma volume AND the interstitial fluid spaces • Angiotensin II – does not just lead to aldosterone release; it is a very potent molecule in its own right • Aldosterone – increases sodium retention and potassium loss in the kidney; but also acts on the myocardium and vascular tree Maladaptive Effects of Angiotensin II Cardiac Myocyte Fibroblast Hypertrophy Hyperplasia Apoptosis Collagen synthesis Cell sliding Fibrosis Increased wall stress Increased O2 consumption Peripheral Artery Coronary Artery Vasoconstriction Endothelial dysfunction Hypertrophy Decreased compliance Vasoconstriction Endothelial dysfunction Atherosclerosis Thrombosis Impaired relaxation (Mostly via AT1 receptor activation) Maladaptive Effects of Aldosterone Cardiac Myocyte Fibroblast Peripheral Artery Kidney Hypertrophy Norepinephrine release Hyperplasia Collagen synthesis Fibrosis Vasoconstriction Endothelial dysfunction Hypertrophy Decreased compliance Potassium loss Sodium retention A decrease in heart rate is most commonly associated with: a) a decrease in parasympathetic and sympathetic activation b) an increase in parasympathetic activation c) an increase in parasympathetic and sympathetic activation d) an increase in sympathetic activation e) no change in activation of the autonomic nervous system Symptoms/ signs of heart failure • Dyspnoea on exertion • Fatigue • Orthopnoea (dyspnoea when lying flat) • • • • • • Cardiomegaly Fourth heart sound may be audible Oedema (peripheral) Pulmonary venous hypertension Raised JVP Third heart sound may be audilble • Lets have a little think about how these arise? NICE Pathway for Heart Failure https://www.nice.org.uk/guidance/ng106 Treatment of Heart Failure Recap Reading • Henein MY (Ed) Heart failure in clinical practice, 2010, E-book: http://lib.myilibrary.com/Open.aspx?id=292836 Summary:  Define the term heart failure  List conditions that can lead to heart failure  Describe the pathophysiology of heart failure and symptoms/signs in patients  To describe, in outline terms, the treatment options for heart failure Questions?