LANDIOLOL-Training Module-1_AOP_final.pdf

Introduction to Cardiac Arrhythmias Heart Rate control Vasileios Periklis MBA, MSc (owner) Int...

Introduction to Cardiac Arrhythmias Heart Rate control Vasileios Periklis MBA, MSc (owner) International Product Manager AOP Health Confidential For internal use only Do not copy, do not distribute 2 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 3  Table of Contents Module Introduction........................................................................................................................ 5 Chapter 1: Overview of Hemodynamic Control Section 1.1: Hemodynamic Stability in the Critical Care and Perioperative Settings..................................... 6 Section 1.2: Outcomes Related to Inadequate Hemodynamic Control........................................................ 11 Chapter Summary.................................................................................................................................... 15 Chapter 2: Cardiac Arrhythmias Section 2.1: Overview of Cardiac Arrhythmias............................................................................................. 16 Section 2.2: Atrial Fibrillation........................................................................................................................ 29 Chapter Summary.................................................................................................................................... 47 Chapter 3: Perioperative Tachycardia and Heart Rate control Section 3.1: Overview of Perioperative tachycardia and heart rate control................................................ 49 Section 3.2: Treatment.................................................................................................................................. 51 Glossary.......................................................................................................................................... 66 References...................................................................................................................................... 69 2 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute  Acronyms and Abbreviations BP Blood Pressure CABG Coronary Artery Bypass Graft CAD Coronary Artery Disease CO Cardiac Output ECG (or EKG) Electrocardiogram HR Heart Rate IV Intravenous MAP Mean Arterial Pressure SV Stroke Volume SVR Systemic Vascular Resistance SVT Supraventricular Tachycardia VT Ventricular Tachycardia WPW Wolff-Parkinson-White syndrome 4 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute Module Introduction Purpose The purpose of the Module 1 of this Training Manual is to provide information on the importance of hemodynamic control, especially in the context of atrial fibrillation and intraoperative and postoperative tachycardia. The information is critical to understanding the use of landiolol within the approved of its indications. The Training Manual targets the AOP Orphan or any distributor Professionals with responsibility for these products. Overview This module consists of three chapters. Chapter 1 provides an overview of hemodynamic control, including the relationship between heart rate and blood pressure, and the goals of hemodynamic control in the critical care and perioperative settings. The chapter concludes with a discussion of the potential outcomes related to inadequate hemodynamic control. Chapter 2 covers cardiac arrhythmias, with a focus on atrial fibrillation. It addresses the mechanism, pathophysiology, clinical presentation, diagnosis, and treatment of atrial fibrillation, both in the critical care and perioperative settings. Chapter 3 deals with tachycardia and management of heart rate control in the perioperative environment, with a special focus on the role of beta-blockers and recent controversy regarding the use of oral beta-blockers to prevent ischemia. Together, these three chapters help set the stage for the detailed discussions of beta-blockers, including those considered ultra-short acting and highly beta1 selective beta- adrenergic antagonist (landiolol), that follow in later modules. Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 5  Chapter 1: Overview of Hemodynamic Control Section 1.1: Hemodynamic Stability in the Critical Care and Perioperative Settings Learning Objectives: Define hemodynamic stability and hemodynamic control. Outline the goals of hemodynamic control in the critical care and perioperative settings. Explain the relationship between heart rate and blood pressure, and their roles in hemodynamic control. Hemodynamic stability Hemodynamics deals with blood flow and the forces the heart must develop to circulate blood through the cardiovascular system. Adequate blood flow is essential for adequate supply of oxygen to tissues, which in turn is essential for cardiac health, stability during surgery, and long-term survival.1 The body’s demand for oxygen varies depending on metabolic conditions, age, and factors such as exercise. For example, during exercise, increased metabolic activity in contracting skeletal muscles requires large increases in oxygen and enhanced removal of metabolic wastes, such as carbon dioxide and lactic acid. To meet this demand, blood vessels within the affected muscles dilate to increase blood flow. To maintain arterial pressure throughout the cardiovascular system, cardiac output is increased by increasing heart rate and blood vessels in other organs are constricted.2 Thus, a healthy cardiovascular system maintains adequate supply of oxygen to all tissues by dynamically balancing the factors that affect blood pressure and blood flow.1 Hemodynamic control For most patients, even in the perioperative setting, blood flow is not measured perioperative: during the time including preoperative, or managed directly. However, the basic cardiovascular hemodynamic equations intraoperative, and (see below) show that Mean Arterial Pressure (MAP) is the product of Cardiac postoperative periods Output (CO) and Systemic Vascular Resistance (SVR), and in turn, cardiac output is the product of Heart Rate (HR) and Stroke Volume (SV).2 3 6 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute  MAP = CO x SVR mean arterial pressure = cardiac output x systemic vascular resistance CO = HR x SV cardiac output = heart rate x stroke volume In other words, changes in heart rate affect cardiac output, and changes in blood pressure occur due to changes in systemic vascular resistance or changes in cardiac output. Hemodynamic control, then, is balancing heart rate and blood pressure to maintain hemodynamic stability. In the critical care and perioperative settings, in general, the goals of hemodynamic control are to avoid: hypertension: elevated blood pressure hypertension hypotension: low blood pressure hypotension tachycardia: rapid heart rate tachycardia bradycardia: slow heart rate bradycardia Relationship between heart rate and blood pressure The challenge is that heart rate and blood pressure are not independent. Changes in heart rate may increase or decrease blood pressure depending on other factors. For example, a very slow heart rate can reduce blood pressure through reduced cardiac output. When HR is reduced, CO (which is HR x SV) and MAP are reduced based on the equation: MAP = CO x SVR.2 On the other hand, if the heart is beating very rapidly, or in an uncoordinated fashion, such as occurs with atrial fibrillation, the ventricles may not be pumping efficiently and blood pressure may be reduced due to lower cardiac output.3 Moreover, some drugs used for different aspects of hemodynamic control, such as beta-blockers and calcium channel blockers, may affect both heart rate and blood pressure. So, for example, treatment for tachycardia to bring heart rate to acceptable levels may result in hypotension.1 Balancing this trade-off is a critical challenge in the perioperative and critical care settings. The above equation is key to understand how cardiac output can be maintained while decreasing heart rate as described in the figure below. It will be reviewed again in modules focusing on landiolol mechanism of action. Indeed, with landiolol, a highly cardioselective and short acting β1 antagonist with a unique molecule structure, clinicians have a new, precise treatment option to reduce heart rate, with strongly limited negative effect on blood pressure and contractility of the heart. Due to its innovative characteristics, landiolol represents an improvement in management of ventricular rate in patients in the perioperative and critical care settings, improving their hemodynamic status.4 5 Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 7  A reduction in heart rate not always leads to a drop in blood pressure. BP = CO x SVR Blood Cardiac Systemic Vascular Pressure Output Resistance BP = HR x SV x SVR Blood Heart Stroke Systemic Vascular Pressure Rate Volume Resistance Under certain circumstances (e.g., in case of Atrial Fibrillation) a significantly increased heart rate may lead to a drop in stroke volume, as the heart is beating so fast that there is not enough time for the ventricle to be filled. Landiolol may help increasing the stroke volume while simultaneously reducing the heart rate and only slightly changing the blood pressure. BP = HR x SV x SVR KEY FACT: In Contrast to Other Heart Rate Control Agents, LANDIOLOL Has Limited Effect on Blood Pressure Many heart rate control drugs, such as β-blockers, successfully slow Landiolol represents the heart rate to targeted levels. However, in patients with atrial a true innovation that fibrillation and other conditions in which heart rate control is required, controls heart rate with these drugs can also reduce blood pressure to dangerous levels. limited effect on blood pressure and heart Landiolol is a highly selective ß1 antagonist, with limited effect on contractility. blood pressure and heart contractility. 4 5 8 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute Section 1.2: Outcomes Related to Inadequate Hemodynamic Control Learning Objectives: Identify adverse outcomes associated with inadequate hemodynamic control in the critical care and postoperative settings. Identify patients at risk for complications due to inadequate hemodynamic control. Adverse outcomes associated with inadequate hemodynamic control Inadequate hemodynamic control represents a major risk factor for adverse outcomes both in critical care and perioperative settings. In critical care, inadequate hemodynamic control that results in hypertension or tachycardia increases the risk for developing myocardial ischemia, myocardial infarction, stroke, heart failure, and renal insufficiency.6 7 Inadequate hemodynamic control that results in severe or prolonged hypotension or bradycardia can lead to tissue hypoxia, metabolic acidosis, hypotensive hypoxia: deficiency in oxygen supply to tissues shock, stroke or death.2 The relationship between inadequate hemodynamic control and adverse acidosis: decrease in the pH of blood or body tissues outcomes is especially problematic in postoperative settings because the body activates several protective physiologic responses following surgery. For example, a significant catecholamine surge occurs after surgery, producing catecholamines: adrenal hormones (e.g., dopamine, epinephrine, and measurable elevation in heart rate and blood pressure. Such responses can norepinephrine) that are released be hazardous in the postoperative setting, leading to cardiovascular into the blood during times of physical or emotional stress complications in a significant number of patients undergoing cardiac or non- cardiac surgery.8 In reviews of several studies of patients undergoing non- cardiac surgery, cardiovascular complications, such as myocardial infarction, cardiac arrest, and cardiac death occurred in 1.4% of adults 50 years of age or older, and i n 3.9% of patients who had or were at risk of cardiac disease following non-cardiac surgery.8 Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 11  Patients at risk for hemodynamic complications Not all patients are at equal risk for complications, potentially resulting of inadequate hemodynamic control. Examples of patients at risk include the following: Noncardiac surgical patients with high cardiac risk7 Aging, comorbid patients with risk of postsurgical supraventricular comorbid: presence of one or more tachycardia7 disorders (diseases) in addition to a primary disorder Neurosurgical patients with intraoperative tachycardia and postsurgical hypertension9 Cardio-Thoracic Surgery Patients Post-Coronary Artery Bypass Graft (CABG) surgery patients with a history of hypertension9 Patients with mitral valve surgery, surgical aortic dissection, or mitral valve surgery: surgery to aortic valve replacement with atrial fibrillation repair or replace the mitral valve, the valve through which blood flows from the left atrium to the left Patients with combined CABG and valve surgery9 ventricle surgical aortic dissection: surgical procedure to repair or remove a Patients in the telemetry unit or emergency department presenting section of the aorta in which the with acute onset atrial fibrillation and/or non-compensatory sinus inner and middle layers of the vascular tissue have separated tachycardia7 telemetry unit: hospital unit in which critical care patients are under continuous electronic monitoring no compensatory sinus tachycardia: rapid heartbeat that does not result from a compensatory adjustment by the circulatory system; opposite of compensatory sinus tachycardia, a condition in which the heart rate reflects a compensatory adjustment to conditions such as low blood pressure or low blood volume 12 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute Chapter Summary Hemodynamic control is balancing heart rate and blood pressure to maintain hemodynamic stability. In critical care and perioperative settings, the general goals of hemodynamic control are to avoid hypertension, hypotension, tachycardia, and bradycardia. The therapeutic challenge is that heart rate and blood pressure are not independent. Moreover, some drugs used for different aspects of hemodynamic control, such as beta-blockers and calcium channel blockers, may affect both heart rate and blood pressure. Balancing the complex interplay between blood pressure and blood flow is an important challenge in both the critical care and perioperative settings. Inadequate hemodynamic control represents a major risk factor for adverse outcomes. In critical care, inadequate hemodynamic control, such as hypertension or tachycardia, increases the risk for developing myocardial ischemia, myocardial infarction, stroke, heart failure, and renal insufficiency. Inadequate hemodynamic control that results in severe or prolonged hypotension or bradycardia can lead to tissue hypoxia, metabolic acidosis, hypotensive shock, stroke or death. The relationship between inadequate hemodynamic control and adverse outcomes is especially problematic in postoperative settings because the body activates several protective physiologic responses following surgery. In reviews of several studies of patients undergoing non-cardiac surgery, cardiovascular complications, such as myocardial infarction, cardiac arrest, and cardiac death occurred in 1.4% of adults 50 years of age or older, and in 3.9% of patients who had or were at risk of cardiac disease following non- cardiac surgery. Patients at risk for complications due to inadequate hemodynamic control include: noncardiac surgical patients with high cardiac risk; aging, comorbid patients with risk of postsurgical supraventricular tachycardia; neurosurgical patients with intraoperative tachycardia and postsurgical hypertension; post- CABG surgery patients with a history of hypertension; patients with mitral valve surgery, surgical aortic dissection, or aortic valve replacement with atrial fibrillation; patients with combined CABG and valve surgery, and; patients in the telemetry unit or emergency department presenting with acute onset atrial fibrillation and/or non-compensatory sinus tachycardia. Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 15  Chapter 2: Cardiac Arrhythmias Section 2.1: Overview of Cardiac Arrhythmias Learning Objectives: Define arrhythmia and differentiate among the different types of cardiac arrhythmias. Describe the basic pathophysiology of cardiac arrhythmias. Describe the diagnosis and treatment of cardiac arrhythmias. Arrhythmia arrhythmia: any variation from the normal Cardiac arrhythmia is a general term that refers to any variation from the sinus rhythm of the heartbeat, including normal sinus rhythm of the heartbeat, including abnormalities of heart abnormalities of heart rate and regularity rate and regularity. In the normally functioning heart, the electrical sinus rhythm: normal heart rhythm impulse generated in the Sinoatrial (SA) node is transmitted through the originating in the sinoatrial node atria to the Atrioventricular (AV) node, then to the bundle of His, the right sinoatrial (SA) node: collection of and left bundle branches, and the Purkinje fibres in the ventricular specialized cardiac muscle fibres at the myocardium.2 3 10 11 junction of the superior vena cava and the right atrium which initiates the cardiac rhythm; also known as the pacemaker atrioventricular (AV) node: collection of specialized cardiac muscle fibres, located at the bottom of the right atrium, which slows conduction of the electrical impulse from the atria to the ventricles, allowing the atria to complete their contraction bundle of His: collection of specialized muscle fibres which transmits impulses from the AV node to the ventricles Purkinje fibres: specialized cardiac muscle fibres that conduct electrical impulses rapidly to the apex of the heart and then into the walls of the ventricles, completing the path of cardiac conduction Figure 1: Cardiac Conduction System 8 16 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute If components of the cardiac conduction system are damaged or dysfunctional, arrhythmias may develop. Some arrhythmias are harmless, while others can be life threatening. Types of arrhythmias Arrhythmias are classified based on the rate and regularity of the heartbeat as well as the source of the electrical impulse. Normal resting heart rate is about 60 to 100 bpm and originates in the sinoatrial node.13 A heart rate slower bradyarrhythmia: abnormal heart than 60 bpm is referred to as bradycardia.14 Bradyarrhythmia is an rhythm associated with a slow heart rate abnormal heart rhythm with low heart rate. Tachycardia is a rapid heart rate, usually defined as more than 100 bpm. tachyarrhythmia: abnormal heart Tachyarrhythmia is a rhythm disturbance associated with rapid heart rate.13 rhythm associated with a rapid heart rate Sinus node arrhythmias occur through misfiring of the sinoatrial node. supraventricular tachycardias (SVTs): Supraventricular arrhythmias, including the Supraventricular Tachycardias tachycardias that originate in tissue above the ventricles (e.g., the atria) (SVTs), the most common of which is atrial fibrillation, originate, at least in part, in atrial tissue above the ventricles. Ventricular Tachycardia (VT) ventricular tachycardias (VTs): originates in ventricular tissue or Purkinje fibres.13 tachycardias that originate in the ventricles In terms of heartbeat regularity, fibrillation is very rapid and uncoordinated fibrillation: very rapid, uncoordinated contractions,3 and flutter is a rapid, but fairly regular heartbeat.3 Atrial contractions of the cardiac muscle that result in irregular heart rhythm fibrillation can lead to pooling of blood and clot formation within the heart, which may lead to stroke. Ventricular fibrillation is a life- threatening flutter: rapid, fairly regular heart rhythm emergency in which the heart is not pumping blood into the circulatory system.3 SV Tachyarrhythmias are classified as atrial or AV nodal tachyarrhythmia: Atrial tachyarrhythmias include sinus tachycardia, inappropriate sinus tachycardia (IST), atrial fibrillation, atrial flutter, sinus nodal reentrant tachycardia (SNRT), and multifocal atrial tachycardia (MAT). -AV tachyarrhythmias include AV nodal reentrant tachycardia (AVNRT), AV reentrant tachycardia (AVRT), junctional ectopic tachycardia (JET), and no paroxysmal junctional tachycardia (NPJT). If the arrhythmia is recurrent and has abrupt onset and termination, then it is designated paroxysmal. This is in contrast to sinus tachycardias, which accelerate and terminate gradually. Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 17  Incidence of arrhythmias Incidence SVT versus AFib/Aflut in ED Usually, paroxysmal SVT account for less than 10% of arrhythmia diagnosed in Emergency Department (ED) when Atrial Fibrillation/Atrial Flutter represent more than 50%15 Patients presenting in ED with paroxysmal SVT are estimated at 14-23 cases per 100 000 inhabitants as compared to 60-120 cases per 100 000 inhabitants for Atrial Fibrillation/Atrial Flutter.16 17 Atrioventricular nodal reciprocating tachycardia (AVNRT) is the most common form of PSVT (Paroxysmal Supraventricular Tachycardias)18 Occurrence of atrial fibrillation after surgery and in intensive care unit19 ICU Population Subset Incidence of new-onset AF General non-cardiac 5%–9% Pulmonary surgery 8%–22% Surgical ICU Pneumonectomy 10%–23% Esophagectomy 22% General medical ICU patients 10%–20% Nonthoracic surgery 10% Medical ICU Septic shock 17% Cardiac surgery ICU/CCU Postoperative cardiac surgery 10%–65% 18 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute  KEY FACT: Ventricular Tachycardia Ventricular tachycardia is an arrhythmia arising in the ventricles.10 Sustained ventricular tachycardia is a life-threatening arrhythmia that usually occurs in patients with underlying heart disease, such as prior myocardial infarction, cardiomyopathy or valvular disease associated with fibrosis, or ventricular enlargement. It can degenerate into ventricular fibrillation, hemodynamic collapse, and sudden death.10 The goals for treatment of ventricular tachycardia are to terminate the arrhythmia and prevent recurrence or sudden death. Treatment options include drugs or electric current to reset the heart or ablation of the part of the heart thought to be responsible for the premature depolarization using electrical or radiofrequency energy. Treatment options also include implantable devices and surgery.11 Mechanisms of arrhythmias Arrhythmias may result from defects in how the electrical signal that triggers the heartbeat is generated (impulse generation), or in how the signal moves through the heart (impulse conduction).20 Disorders of impulse generation. Electrical impulses are generated in the heart by pacemaker cells in the sinoatrial node.2 Pacemaker cells have no true resting potential. Instead of remaining at a stable level until an electrical stimulation arrives from a neighboring cell, pacemaker cells continuously depolarize on their own, generating a spontaneous electrical “firing” of the cell.2 The spontaneous, impulse- generating capacity of pacemaker cells is called automaticity.14 In disorders of impulse generation, the sinoatrial node fires at the wrong rate, or pacemaker cells elsewhere in the heart, that are normally suppressed by impulses generated by the sinoatrial node, fire inappropriately.20 hypokalemia: potassium deficiency This process, which is called enhanced automaticity, is shown in Figure 2. in the blood It can result from changes in autonomic nervous system activity or ischemia: inadequate supply of complications caused by heart disease, such as hypokalemia and blood to an organ or region of the ischemia. These conditions can increase spontaneous depolarization of body, especially the heart muscles pacemaker cells, resulting in increased spontaneous firing. Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 19  Figure 2: Enhanced Automaticity Disorders of impulse conduction. Alterations in how the electrical signal moves through the heart can also cause arrhythmias. The most common type of these impulse conduction disorders is re- entry. Normal action potential impulses begin in the sinoatrial node and travel through the heart in one direction (antegrade conduction) until the entire heart has antegrade conduction: forward conduction of the electrical signal been activated, and the the impulse stops.20 in the heart from the sinoatrial node to the atrioventricular node In the healthy heart, the electrical signal travels quickly enough so that each cell only and into the ventricles responds once per impulse. Cardiac tissue is transiently refractory to re-stimulation; that is, cardiac tissue is unable to respond to a second impulse arriving very close to the first. This helps keep the impulse traveling in a single direction through the heart.20 Re-entry is an abnormal state in which an impulse travel repeatedly in a tight circle within the heart.21 As shown in Figure 3, re-entry can occur when an area of damaged tissue in the heart delays or blocks one of the conduction pathways. This block allows the impulse to repeatedly exit and re- enter that area of the heart.2 21 22 20 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute Figure 3: Re-entry and Retrograde Conduction through an Area with Unidirectional Block2 The forward impulse may be delayed long enough for the normal surrounding tissue to reset and then be re-triggered by an impulse traveling in the opposite, or retrograde, direction. If the timing is right, re-entry may cause a self-perpetuating abnormal conduction cycle, with the impulse repeatedly traveling backward through the blocked region.21 As shown in Figure 4, re-entry can take place in a small local region within the heart, or it can occur more globally within the entire atrium or ventricle, or even along pathways involving both atria and ventricles. Figure 4: Local and Global Re-entry 2 Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 21  A re-entry circuit can be started by an anatomical or functional block in a region of the heart.22 A local disturbance that slows conduction of the forward electrical signal can, if the timing is right, lead to a re-entry circuit.22 Extensive fibrosis due to heart disease is an example of an anatomical block. fibrosis: formation of fibrous tissue Functional barriers that may lead to re-entry include acute myocardial ischemia and ion channel abnormalities.22 Diagnosis of arrhythmias Some arrhythmias may be highly symptomatic and may not be associated with any adverse outcome, whereas some patients with other arrhythmias have no symptoms at all but may still be at significant risk of adverse outcomes.23 In some cases, patients present with symptoms of an arrhythmia, such as palpitations, syncope, or worsening heart failure. In others, the physician might syncope: temporary loss of consciousness caused by a fall have reason to suspect an arrhythmia in an asymptomatic patient. In all cases, the in blood pressure (i.e., diagnostic process begins by taking a thorough medical history and doing a physical fainting) exam.23 Medical history. As part of the medical history, the physician may ask questions focused on when and under what circumstances (such as exercise, emotional stress, physical position, ingestion of a particular food or substance) the symptoms begin and stop, what medications the patient is taking, and what other medical conditions the patient has that might predispose him or her to an arrhythmia. The physician will also inquire about family history. The patient’s answers help the physician decide which, if any, diagnostic tests to order.23 Physical exam. A physical exam for suspected arrhythmia generally includes an assessment of blood pressure, heart rate, heart sounds, and other factors that might indicate an underlying structural problem in the patient’s heart.23 Electrocardiogram (ECG or EKG). The first diagnostic test the physician is most likely to order is the ECG to capture a complete multidimensional picture of the electrical activity occurring in the patient’s heart. If an arrhythmia occurs during the test, the result will be diagnostic.23 However, an arrhythmia may not occur during testing, so the ECG is not always definitive. It can, however, provide clues about structural or physiological abnormalities that could have caused an arrhythmia at another time.23 22 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute Figure 5 shows characteristic patterns of atrial fibrillation and atrial flutter. Figure 5: ECG Patterns of Cardiac Arrhythmias 17 Treatment of arrhythmias Lifestyle modifications (e.g., reducing alcohol and caffeine intake) and treatment of underlying medical conditions that may precipitate arrhythmias are early steps in their management. When a patient has an arrhythmia that is serious enough to merit treatment beyond lifestyle modification, clinicians may choose:25 drug therapy cardioversion: process to restore normal sinus rhythm using drugs or cardioversion electrical shock cardiac catheter ablation cardiac catheter ablation: procedure to restore normal sinus rhythm by implantation of a pacemaker destroying the tissue responsible for the rhythm disorder implantation of a cardioverter defibrillator surgery Each of these treatment options are described below. Some patients require only one of these options; others require a combination of two or more. Treatment depends on the specific arrhythmia.25 Drug therapy. Drug treatment for arrhythmias consists of antiarrhythmic agents. These types of drugs have electrophysiological effects in cardiac tissue, and either speed up or slow down the transmission of impulses at different points in the cardiac conduction system. Thus, they affect heart rate and rhythm in different ways, depending on the source of the problem.25 The Vaughan Williams classification of antiarrhythmic drugs is used extensively worldwide to classify antiarrhythmic agents. Table 1 presents this classification, which groups antiarrhythmic drugs into four main classes based on the primary mechanism of action of the drugs.258 Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 23  Table 1: Vaughan Williams Classification of Antiarrhythmic Agents26 Class Description Examples Mechanism Na+ channel block (intermediate association Disopyramide /dissociation) and K+ channel blocking effect; IA Sodium channel blockers Procainamide affects QRS complex. Class IA agents prolong Quinidine the action potential and have intermediate effect on the 0 phase of depolarization. Na+ channel block (fast association /dissociation); can prolong QRS complex in Lidocaine IB overdose. Class IB agents shorten the action Mexiletine potential of myocardial cell and have weak effect on initiation of phase 0 of depolarization. Na+ channel block (slow association/ Flecainide dissociation) has no effect on action potential IC Propafenone and has the strongest effect on initiation phase 0 the depolarization. Landiolol Esmolol Beta blocking. Propranolol also shows some II Beta-blockers Metoprolol class I action. Propranolol Amiodarone Bretylium K+ channel blocker III Potassium channel blockers Dofetilide Sotalol is also a beta blocker. Amiodarone has Ibutilide Class III mostly, but also, I, II, & IV activity. Sotalol Nondihydro- IV pyridine Calcium channel blockers Ca2+ channel blocker Diltiazem Verapamil Adenosine Digoxin Work by other or unknown mechanisms (direct V Magnesium nodal inhibition). Sulfate 24 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute  Class I agents are primarily sodium channel blockers. These drugs bind to and block the fast sodium channels that are responsible for the rapid depolarization of fast-response cardiac action potentials. These drugs can also block potassium channels.25 Class II agents are beta-blockers. Beta-blockers bind to beta receptors located on cardiac tissues. This binding blocks the catecholamines (i.e., norepinephrine and epinephrine), thereby slowing the rate at the sinoatrial node and the conduction velocity, increasing the refractory period of AV node, while also decreasing spontaneous firing of ectopic pacemakers.25 Class III agents block potassium channels. These agents delay repolarization and increase the action potential duration and refractoriness of cardiac fibres.25 Class IV agents are calcium channel blockers. These agents block calcium channels and suppress electrical activity in the normal sinus and AV nodes.25 Class V agents do not fit clearly into categories I through IV. These agents work by unknown or other mechanisms (e.g., Digoxin reduces electrical activity through the AV node).25 Cardioversion. In cardioversion, antiarrhythmic drugs are used, or an electrical shock is delivered to the heart to quickly restore the sinus rhythm. This shock can be delivered externally, via a defibrillator, or internally by a device similar to a pacemaker, called an implantable cardioverter defibrillator. Cardiac catheter ablation. Cardiac catheter ablation is performed using electrotherapy. An electrode catheter is threaded up to the site in the heart where the arrhythmia originates, and radiofrequency energy is applied to the area. This energy destroys the tissue thought to be responsible for the arrhythmia.18 Implantation of a pacemaker. An artificial pacemaker is a device used to compensate for inadequate electrical stimulation of the heart by providing an external source of stimulation. The pacemaker consists of a lithium battery and wires that are sewn into the patient’s right atrium, the right ventricle, or both, as needed. Pacemakers are used to accelerate heart rate in patients with dangerous bradycardias or to correct heart block.20 Implantation of a cardioverter defibrillator. Like the pacemaker, an implantable cardioverter defibrillator is a small device that is connected to the heart to deliver electrical signals as needed. However, in addition to the low-level current to correct bradycardia, the stronger defibrillator can also shock the heart to correct more serious arrhythmias such as ventricular fibrillation, ventricular tachycardia, and atrial fibrillation. These devices are used in patients who have experienced ventricular tachycardia or fibrillation, whose histories suggest they are at risk, as well as in patients whose atrial fibrillation is not well controlled.28 Surgery. Cardiac catheter ablation has largely replaced open surgery as the treatment of choice. For patients who have not responded to drug therapy or cardiac catheter ablation, however, surgery may be an option. If performed, the goal of surgery is to remove the tissue causing the problem without harming heart function.25 Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 25 Section 2.2: Atrial Fibrillation Learning Objectives: Identify the risk factors associated with atrial fibrillation. Describe the pathophysiology of atrial fibrillation. List the clinical manifestations of atrial fibrillation. Describe potential complications, specific risk factors, and onset of perioperative and postoperative atrial fibrillation. Describe the diagnostic criteria for atrial fibrillation. Outline treatment options for atrial fibrillation. Overview Atrial fibrillation is the most common arrhythmia treated in clinical practice and the most common arrhythmia for which patients are hospitalized.29 In the United States, the estimated prevalence of atrial fibrillation is expected to double between 2010 and 2050 as shown in Table 2.30 Table 2: Estimated Prevalence of Atrial Fibrillation in the United States 30 Year Estimated Prevalence 2010 2.7 to 6.1 million 2050 5.6 to 12 million Atrial fibrillation is associated with an increased risk of heart failure, an approximately five-fold increase in the risk of stroke, and a two-fold increase in the risk of all-cause mortality.30 Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 29  Risk factors Data from the Framingham Heart Study show that the lifetime risk for developing atrial fibrillation after age 40 is 26% for men and 23% for women. The incidence of atrial fibrillation is age- and gender-related, ranging from 0.1% per year before the age of 40 in both women and men to more than 1.5% per year in women and more than 2% per year in men older than 80 years.29 In addition to advancing age, risk factors for atrial fibrillation include:29 congestive heart failure aortic and mitral valve disease left atrial enlargement hypertension obesity obstructive sleep apnea Patients undergoing surgery, especially thoracic and cardiac surgery, are also at risk for developing postoperative atrial fibrillation. Classification Atrial fibrillation is classified as follows29-33: First diagnosed atrial fibrillation refers to atrial fibrillation that has not been diagnosed before, irrespective of the duration of arrhythmia or the presence and severity of symptoms.32 Paroxysmal atrial fibrillation is recurrent atrial fibrillation that lasts less than a week (typically less than 48 hours) and that converts spontaneously to normal sinus rhythm.23 AF episodes that are cardioverted (intervention) within 7 days should be considered paroxysmal according to 2016 ESC AF guidelines. Persistent atrial fibrillation lasts more than a week and requires treatment to convert to normal sinus rhythm.33 Permanent atrial fibrillation is used when the patient and physician make a decision to stop further attempts to control sinus rhythm.31 32 Longstanding atrial fibrillation is continuous atrial fibrillation lasting for ζ 1 year.31 32 The longer atrial fibrillation is present, the less likely spontaneous conversion will occur and the more difficult cardioversion becomes.32 Longstanding atrial fibrillation that doesn’t respond to cardioversion is considered permanent. However, “permanent” atrial fibrillation is not necessarily permanent in the literal sense because it still may be successfully eliminated by surgical or catheter ablation.32 30 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute  This classification system is not applied to patients with atrial fibrillation secondary pericarditis: inflammation of to cardiac surgery, acute myocardial infarction, pericarditis, myocarditis, the membrane that surrounds hyperthyroidism, or acute pulmonary disease. Generally, in these situations, the the heart atrial fibrillation terminates with treatment of the underlying condition and may myocarditis: inflammation of not recur unless the underlying condition recurs.26 heart muscle tissue Pathophysiology Normal atrial depolarization results in synchronous contractions of each atrium that pump blood into the ventricles, which then pump it into the systemic (left ventricle) or pulmonary (right ventricle) circulation. With atrial fibrillation, instead of normal depolarization and synchronous contractions, the atria quiver erratically and do not provide effective pumping, resulting in incomplete ventricular filling and reduced cardiac output. The ineffective atrial quivering also causes blood to stagnate in the atria, particularly in the left atrial appendage, which can lead to thromboembolic complications such as stroke. Atrial fibrillation is characterized by disorganized, rapid, and irregular fibrillations caused by abnormal atrial depolarizations. These depolarizations occur between 300 and 600 times per minute. The depolarizations also affect the ventricles. With atrial fibrillation, the ventricular rate is elevated, but usually much slower than the atrial rate, typically between 100 and 160 bpm, because the atrioventricular node limits the speed of conduction from the atria to the ventricles.29 In atrial fibrillation, the ventricular rate is important because the ventricles pump blood to the lungs and the rest of the body. As such, rapid, irregular ventricular rhythm can cause serious and life- threatening symptoms. In some rare conditions, such KEY FACT: Beta-Blockers Are Wolff-Parkinson-White as Wolff-Parkinson- White not Used for Wolff-Parkinson- (WPW) syndrome: type of (WPW) syndrome, 34 35 the supraventricular tachycardia White Syndrome characterized by an extra or ventricular rate can be higher accessory conduction pathway than 250 bpm in the presence of In Wolff- Parkinson-White syndrome, impulses flow from the atria to the ventricles through an accessory atrial fibrillation, which can lead or alternate pathway instead of the normal passage of to ventricular fibrillation and impulses through the atrioventricular node to the death. Wolff-Parkinson-White ventricles.34,35 syndrome occurs Conduction progresses from the atria with antegrade conduction through the AV node to the ventricle and retrograde conduction through the accessory pathway, or conduction progresses with antegrade conduction passing from the atria through the accessory pathway to the ventricle.34,35 If conducting retrograde, beta-blockers or calcium channel blockers can be given, but they should not be given if conducting anterograde as this may increase the frequency of conduction through the accessory pathway to the ventricle, possibly causing ventricular fibrillation.34,35 Clinical guidelines recommend that beta-blockers and calcium channel blockers should be avoided in atrial fibrillation and atrial flutter with Wolff Parkinson White syndrome.34,35 Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 31  because of the presence of a bypass track, or accessory pathway, which conducts electrical activity around the atrioventricular node and thus avoids its limiting effects on the number of impulses that can be conducted to the ventricles. In most patients, the atrioventricular node protects the ventricles from overly rapid stimulation by atrial fibrillatory waves.13 29 Atrial fibrillation may result from defects in how the electrical signal that triggers the heartbeat is generated (disorders of impulse generation), in how the signal moves through the heart (disorders of impulse conduction), or both.26 Atrial tissue fibrosis caused by underlying myocardial disease can create an anatomical conduction barrier that contributes to the development of atrial fibrillation.22 Even after a patient recovers hemodynamically from disease such as congestive heart failure, the fibrosis remains, creating the potential for sustained atrial fibrillation.33 Atrial fibrillation may also arise from an overactive sympathetic nervous system. The sympathetic nervous system reacts to stress, stimulants, etc. causing the heart to speed up and the blood vessels to constrict. This type of atrial fibrillation is called adrenergic atrial fibrillation (adrenaline stimulates the heart to beat faster and stronger when the body demands more oxygen). Adrenergic atrial fibrillation occurs in approximately 10% to 15% of people with paroxysmal atrial fibrillation and high sympathetic nervous system activity, for example during strenuous exertion or in the postoperative setting.29 Clinical manifestations An estimated 25% of patients with atrial fibrillation are asymptomatic. In these patients, the atrial fibrillation is only discovered on routine examination or when the patient is seen for another condition.29 For the remaining 75%, symptoms of atrial fibrillation vary and depend on the patient’s underlying cardiac status as well as the rapidity and irregularity of the ventricular rate. Many patients with atrial fibrillation present with palpitations, vague chest discomfort, and/or symptoms of heart failure such as weakness, lightheadedness, or dyspnea.33 These symptoms particularly occur in patients dyspnea: difficult or labored breathing with a rapid ventricular rate (e.g., 140 to 160 bpm).33 The hallmark sign of atrial fibrillation on physical examination is an irregular pulse. Rapid ventricular contractions result in a low stroke volume. This results in a “pulse deficit”, in which the pulse at the wrist is not as rapid as the ventricular rate at the heart. Other signs of atrial fibrillation include irregular jugular venous pulsations and variable intensity on the first heart sound.29 32 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute  Atrial fibrillation can result in serious hemodynamic consequences due to thromboembolism: obstruction of reduced cardiac output or thromboembolism. The risk of these complications a blood vessel due to a blood clot carried by the blood stream depends on a number of factors, including the ventricular rate, concomitant conditions such as hypertension, and heart failure, and the patient’s age.29 As mentioned previously, the mortality rate in patients with atrial fibrillation is about twice that of patients with normal sinus rhythm. Perioperative atrial fibrillation Preoperative atrial fibrillation is associated with an increased risk for perioperative mortality and morbidity, late mortality, and recurrent cardiovascular events in patients undergoing cardiac surgery.36 Atrial fibrillation is also the most common complication following cardiac surgery, and it is the most common reason for prolonged hospitalization after surgery. As shown in Table 3, the overall incidence of postoperative atrial arrhythmias among elderly patients after major non-cardiac surgery is 4%.37 After cardiothoracic surgery, the incidence is much higher for all patients, up to 50%.36 Table 3: Estimated Incidence of Postoperative Atrial Fibrillation 31 36 37 Population Estimated Incidence Elderly patients after major non- cardiac surgery 4% All patients who undergo coronary artery bypass 35% to 50% graft surgery or valve replacement Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 33  Postoperative atrial fibrillation is also associated with an increased risk of KEY FACT: Age Is a mortality and morbidity and predisposes patients to a higher risk of Key Risk Factor for stroke.38 As with atrial fibrillation in other settings, the stagnation of blood Atrial Fibrillation in the atria due to incomplete emptying into the ventricles puts the patient at risk for thromboembolic events. In several studies, age of 60 years or older has been a consistent preoperative risk Risk factors. Preoperative risk factors associated with increased risk for factor for atrial fibrillation following cardiothoracic surgery include:37-39 increased incidence of atrial arrhythmias, including atrial fibrillation, following advanced age surgery.36 37 history of previous atrial fibrillation male gender decreased left ventricular ejection fraction2 left ventricular ejection fraction: proportion of blood in the left left atrial enlargement ventricle that is ejected (pumped) out during contraction chronic lung disease diabetes obesity Other factors that may contribute to postoperative atrial fibrillation are intraoperative and postoperative atrial injury, inflammation, and increased adrenergic state, such as occurs after a traumatic or strenuous event, such as surgery. Onset. Postoperative atrial fibrillation occurs most often in the first few days after surgery, but it can occur at any point during the recovery period. Figure 6 shows the results from a prospective, observational study of 1,503 patients undergoing CABG surgery. The majority of episodes of atrial fibrillation occurred within the first 3 days after surgery, with a peak on postoperative day 2.39 The reason why atrial fibrillation episodes peaks on day 2 is not well understood, but it may be linked to changes that occur over time after surgery. For example, a significant catecholamine surge occurs after surgery, producing transient measurable elevation in heart rate and blood pressure. Such responses can be hazardous, eventually leading to cardiovascular complications in a significant number of patients.8 34 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute Figure 6: Day of Initial Occurrence for Postoperative Atrial Fibrillation after CABG Surgery 39 Diagnosis of atrial fibrillation Diagnosis of atrial fibrillation is primarily made through evaluation of its characteristic ECG features. As you learned in Module 1 and as is shown in Figure 7, the normal ECG waveform includes the P wave, QRS complex, ST segment, and the T wave. Figure 7: Normal ECG Waveform 2 The P wave represents atrial depolarization, the spread of an electrical stimulus through the atria, resulting in atrial contraction. When a patient is in normal sinus rhythm, each heartbeat begins with atrial depolarization and as can be seen in Figure 8, a normal electrocardiogram clearly shows a P wave preceding each QRS complex.2 Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 35  The QRS complex represents ventricular depolarization as the stimulus travels through the ventricles, resulting in ventricular contraction.2 The ST segment and T wave represent ventricular repolarization, the return of the ventricular muscle to the resting state.2 Figure 8: Normal ECG, Atrial Fibrillation, and Atrial Flutter 24 As shown in Figure 8, atrial fibrillation is characterized by a grossly irregular rhythm. Figure 8 also illustrates the primary difference on ECG between atrial fibrillation and atrial flutter. Atrial fibrillation has an irregular rhythm. Atrial flutter, though fast, has a fairly regular rhythm. 36 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute KEY FACT: Rate versus Rhythm Control There are two approaches to treat atrial fibrillation: Rate control, which slows the heart rate, with the use of beta-blockers, calcium channel blockers, or combination therapy, allowing the heart to return to sinus rhythm spontaneously Rhythm control, which restores and maintains sinus rhythm with the use of antiarrhythmic medications, cardioversion, or both34 Rate control is often sufficient to improve atrial fibrillation symptoms. Rhythm control therapy is indicated to improve symptoms in patients troubled with symptoms on insufficient rate control therapy.32 Several randomized controlled trials have demonstrated that a strategy aimed at restoring and maintaining sinus rhythm neither improves survival nor reduces the risk of stroke. No trials so far have shown superiority of rhythm control in terms of morbidity or quality of life patients with AF. Pharmacological rhythm control is only moderately effective in maintaining sinus rhythm, has potential adverse effects, and does not cure atrial fibrillation; it can postpone or reduce atrial fibrillation recurrences but rarely eliminates atrial fibrillation. 40-48 The largest study by far was the AFFIRM study of 4060 patients with atrial fibrillation. At 5years of follow-up, there was no significant difference between groups of patients receiving rate control or rhythm control in terms of total mortality, stroke, or quality of life. However, the percentage of patients requiring hospitalization and the incidence of adverse drug effects was significantly lower in the rate control arm. As a result of the AFFIRM study, a rate control strategy is considered preferable to a rhythm control strategy in asymptomatic or minimally symptomatic patients 65 years of age or older.29 Atrial fibrillation after cardiac surgery is associated with increased rates of death, complications, and hospitali- zations. According to the 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft (CABG) Surgery, in subjects without pre-CABG AF, post-CABG atrial fibrillation usually resolves spontaneously within 6 weeks of surgery. 42 As a result, the preferred management strategy of post-CABG atrial fibrillation in such patients often consists of control of the ventricular rate (with beta blockers) in anticipation of spontaneous reversion to sinus rhythm within a few weeks.42 Since these guideline release, a prospective randomized trial114 has been comparing rate vs rhythm strategy for patients undergoing cardiac surgery and developing postoperative atrial fibrillation. Patients (n=523) with new-onset postoperative atrial fibrillation were randomly assigned to undergo either rate control or rhythm control. The primary end point was the total number of days of hospitalization within 60 days after randomization. The total numbers of hospital days in the rate-control group and the rhythm-control group were similar (median, 5.1 days and 5.0 days, respectively; P=0.76). There were no significant between-group differences in the rates of death (P=0.64) or overall serious adverse events (24.8 per 100 patient-months in the rate-control group and 26.4 per 100 patient-months in the rhythm-control group, P=0.61), including thromboembolic and bleeding events. About 25% of the patients in each group deviated from the assigned therapy, mainly because of drug ineffectiveness (in the rate-control group) or amiodarone side effects or adverse drug reactions (in the rhythm-control group). At 60 days, 93.8% of the patients in the rate-control group and 97.9% of those in the rhythm-control group had had a stable heart rhythm without atrial fibrillation for the previous 30 days (P=0.02), and 84.2% and 86.9%, respectively, had been free from atrial fibrillation from discharge to 60 days (P=0.41). In conclusion, strategies for rate control and rhythm control to treat postoperative atrial fibrillation were associated with equal numbers of days of hospitalization, similar complication rates, and similarly low rates of persistent atrial fibrillation 60 days after onset. Neither treatment strategy showed a net clinical advantage over the other. 114 A recent survey on Therapies That Are Routinely Applied “Prophylactically” and as “Treatment” to Cardiac Surgical Patients at High Risk of Developing Atrial Fibrillation was included in a Practice Advisory for the Management of Perioperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery released by European and American Societies of Anesthesiology. 80% of US responders use Beta-blockers (rate control) and 93% of US responders use amiodarone (rhythm control) 115 Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 37  Treatment of atrial fibrillation in the critical care setting The goals of treating atrial fibrillation include:31 controlling ventricular rate restoring and maintaining sinus rhythm preventing thromboembolism Strategies used to achieve these goals are individualized for each patient based on patient characteristics, symptoms, ventricular rate, underlying conditions, and other factors. The treatment options described in this section are those recommended by the 2014 AHA/ACC/HRS Guidelines 31, revised in 2019116 and the 2016 ESC Guidelines for the management of atrial fibrillation developed in collaborate on with EACTS32 revised successively in 2020117 and more recently in 2024. 118 American Guidelines for rate control in patients with AF116 US guidelines for management of AF: 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation KEY FACT: 2019 US Guidelines for Rate Control Beta-blockers are Class-I recommendation for rate control as well as Calcium Blocker in AF guidelines In case of hemodynamic instability, electrical cardioversion is indicated Intravenous Amiodarone “can be useful” for rate control in critically ill patients. (Class IIa) Landiolol is of course not yet listed in the beta-blocker list but esmolol is listed. (Table 10 – 2014 guidelines) Most recommendations are similar to European guidelines 38 AOP Health Confidential For Internal Use Only Do Not Copy or Distribute European Recommendations for ventricular rate control in patients with AF118 Recommendations Classb Levelc Rate control therapy is recommended in patients with AF, as initial therapy in the acute setting, an adjunct to rhythm control therapies, or as a sole treatment strategy to control heart rate and reduce I B symptoms. Beta-blockers, diltiazem, verapamil, or digoxin are recommended as first-choice drugs in patients with I B AF and LVEF >40% to control heart rate and reduce symptoms. Beta-blockers and/or digoxin are recommended in patients with AF and LVEF ≤40% to control heart rate I B and reduce symptoms. Combination rate control therapy should be considered if a single drug does not control symptoms or IIa C heart rate in patients with AF, providing that bradycardia can be avoided, to control heart rate and reduce symptoms. Lenient rate control with a resting heart rate of < 110 b.p.m. should be considered as the initial target for patients with AF, with stricter control reserved for those with continuing AF-related symptoms. IIa B Atrioventricular node ablation in combination with pacemaker implantation should be considered in IIa B patients unresponsive to, or ineligible for, intensive rate and rhythm control therapy to control heart rate and reduce symptoms. Atrioventricular node ablation combined with cardiac resynchronization therapy should be considered in severely symptomatic patients with permanent AF and at least one hospitalization for IIa B HF to reduce symptoms, physical limitations, recurrent HF hospitalization, and mortality. Intravenous amiodarone, digoxin, esmolol, or landiolol may be considered in patients with AF who have © ESC IIb B haemodynamic instability or severely depressed LVEF to achieve acute control of heart rate. Figure 9: Acute heart rate control in patients with atrial fibrillation according to 2024 EFC Guidelines. 25 Ventricular rate control. The ventricular rate of patients with acute atrial fibrillation may be controlled pharmacologically with a variety of drugs or with non-pharmacologic therapies such as ablation of the atrioventricular node using heat generated by radiofrequency energy or cryoablation. Control of ventricular rate is important to manage symptoms and prevent the development of tachycardia-related cardiomyopathy.29 In patients with persistent AF, there are fundamentally 2 ways to manage the dysrhythmia: to restore and maintain sinus rhythm or to allow AF to continue and ensure that the ventricular rate is controlled. In persistent or permanent AF, the guidelines recommend rate control with drugs. 31 KEY FACT: 2024 ESC Guidelines for Rate Control In 2020 ESC AF guidelines, for the first time, Landiolol was included in “Western” guidelines, with its inclusion in listed agents for rate control. Landiolol is included as the only agent with a specific dose recommendation in patients with cardiac dysfunction. (dosages of 1 μg/kg/min up to 10 μg/ kg/min) In the 2024 ESC AF guidelines, landiolol has been added to Amiodarone, along with esmolol and digoxin, as an alternative in patients with hemodynamic instability or cardiac dysfunction (Class: IIb, LOE: B) Esmolol, although quoted in the table, is not mentioned in the text when landiolol is quoted twice : “In selected patients who are hemodynamically unstable or with severely impaired LVEF, intravenous amiodarone, landiolol, or digoxin can be used. “ AF-CARE in unstable patients : “The ultra-short acting and highly selective beta- blocker landiolol can safely control rapid AF in patients with low ejection fraction and acutely decompensated heart failure, with a limited impact on myocardial contractility or blood pressure” Do Not Copy or Distribute For Internal Use Only AOP Health Confidential 39  In patients without accessory pathway, intravenous (IV) administration of beta- blockers (esmolol, landiolol), metoprolol, or propranolol) or diltiazem/verapamil is recommended to slow the ventricular response to atrial fibrillation in the acute setting.29 31 In heart failure with reduced ejection fraction, beta-antagonists (first- line), digoxin or their combination should be used.32 While care should be taken to avoid hypotension, landiolol provides a very low risk of hypotension. These drugs act at the atrioventricular node, so they should not be used in cardiomyopathy: chronic disease of the heart muscle patients whose cardiac impulses travel along accessory pathways not subject to the delay of the atrioventricular node, such as occurs in patients with Wolff- Parkinson-White syndrome.33 In patients with accessory pathways, amiodarone is recommended to control heart rate.31 Digoxin is the least effective of the drugs used to control heart rate, but may be preferred in patients with heart failure.33 Patients whose heart rate and blood pressure are stable may be treated orally.31 The key drugs used for the treatment of atrial fibrillation in the critical care setting include beta-blockers, calcium channel blockers, digoxin, and amiodarone. Each of these drugs is discussed below. KEY FACT: Rate control first; Amiodarone is not a first line for rate control The 2020 ESC Guidelines 117 for the management of atrial fibrillation already recommended To perform rhythm control you have to do first an adequate rate control The new 2024 ESC Guidelines118 further reinforce rate control as first line option Rate control is recommended as initial therapy in the acute setting, an adjunct to rhythm control, or as a sole treatment strategy to control heart rate and reduce symptoms. The 2020 ESC Guidelines 117 for the management of atrial fibrillation recommended amiodarone as 2nd line for rate control and contained elements of caution. Amiodarone can be useful as last resort when heart rate cannot be controlled The anti-arrhythmic drugs with rate control properties (amiodarone, sotalol), they should be used only for rhythm control Intravenous amiodarone maybe leads to further decrease of blood pressure in patients with hemodynamic instability The new 2024 ESC Guidelines 118 confirm this statement: Due to its broad extracardiac adverse effect profile, amiodarone is reserved as a last option when heart rate cannot be controlled even with maximal tolerated combination therapy, or in patients who do not qualify for atrioventricular node ablation and pacing. Many of the adverse effects from amiodarone have a direct relationship with cumulative dose, restricting the long-term value of amiodarone for rate control. KEY FACT: New Recommendations for “Strict” vs “Lenient” Rate Control The optimal heart-rate target in AF patients is unclear. In the RACE (Race Control Efficacy in Permanent Atrial Fibrillation) II RCT of permanent AF patients, there was no difference in a composite of clinical events, New York Heart Association (NYHA) class, or hospitalizations between the strict [target heart rate