CVD: Cardiac Arrhythmias 1. Final Cardiac Arrhythmias_BMP 1.1 Cardiovascular Disease
1.2 Directions for taking this course
1.3 Content Experts 1.4 Disclosures
1.5 Accreditation Information 1.6 Learning Objectives
1.7 Cardiac Arrhythmias In a normal heart, the sinoatrial (SA) node generates electrical impulses that spread as a wave of depolarization through the atria and to the atrioventricular (AV) node. The AV node briefly holds the impulse before it is released into the ventricles through the Bundle of His, down the bundle branches, and up the Purkinje fibers. Shortly after the impulse wave spreads through the atria or ventricles, contraction of muscle occurs. You can see that the blood would first be ejected from the atria into the ventricles and then after ventricular depolarization, the ventricles would eject blood either to the lungs or to the brain and rest of the body. Review Contraction of the heart https://www.youtube.com/watch?v=waosupehpqs An arrhythmia is an abnormal alteration of the heart rate or rhythm. Arrhythmias are common occurrences in elderly patients. Ventricular arrhythmias account for 2/3 of cases while arrhythmias occurring above the Bundle of His -- called supraventricular arrhythmias -- account for the remaining third. However, atrial fibrillation is the most common single arrhythmia.
1.8 Cardiac Contraction 1.9 Atrial Fibrillation Atrial fibrillation (AF) is a common arrhythmia encountered in clinical practice that increases in prevalence
with advancing age. About 9% of people aged 65 years or older have AF (CDC); more than one-third of patients with AF are >80 years of age (January et al, 2014). Although men have a higher incidence of AF than women, because the incidence of AF increases dramatically with age and because there are more women in the population older than the age of 75 years, the absolute number of women and men with atrial fibrillation in this age group is equal (Kerr and Humphries, 2005). AF is a supraventricular arrhythmia characterized by an extremely fast and disorganized activity of atrial conducting tissue and consequently ineffective atrial contraction. Multiple re-entrant loops formed within atrial conducting tissue and/or the pulmonary veins are potential sources for developing AF. Review Atrial Fibrillation http://watchlearnlive.heart.org/cvml_player.php?moduleselect=atrfib 1.10 Atrial Fibrillation
1.11 Definitions of Atrial Fibrillation The clinical significance of atrial fibrillation varies from trivial to life threatening, and proper management depends on accurate diagnosis of the rhythm disturbance and knowledge of the clinical circumstances. AF may be defined in terms of the duration of episodes. This is important as the management approach varies depending on how long the patient has been in AF. Recognizing non-valvular versus valvular AF is equally important, as management varies under these conditions as well.
1.12 Atrial Fibrillation Essentially, any condition that alters the structure and/or function of the atrial tissue can lead to the development of AF. It commonly occurs in the setting of conditions that increase metabolic demand(e.g., heart failure), disorders that stretch out the atrial tissue (e.g., hypertension), or local atrial inflammation (e.g., sepsis). The most common conditions associated with the development of AF include ischemic heart disease, hypertension, heart failure and valvular heart disease. AF may also develop from non-cardiac causes, including alcohol withdrawal, infection, electrolyte abnormalities, and can be drug-induced.
1.13 Atrial Fibrillation Patients with atrial fibrillation may be symptomatic or asymptomatic. Common symptoms include palpitations, dyspnea, fatigue, angina, and syncope. Fatigue and dyspnea, however, are commonly found in older adults and are often attributed to old age, which may lead to a delayed diagnosis. In some instances, patients can have a loss of atrial contraction, which can reduce cardiac output. Older adults often rely on contraction of the atria to optimize ventricular filling. This can lead to a reduction in stroke volume and cardiac output, which can precipitate syncopal episodes or heart failure. This loss of contraction and decline in cardiac output creates the potential for blood to pool in the atria and form a clot. As such, some patients initially present with a stroke only to later discover they also have AF.
1.14 Atrial Fibrillation AF is an irregular-irregular heart rhythm, in that both the rate and rhythm are out of sync. A patient in normal sinus rhythm will have a discernable p-wave and evenly spaced QRS complexes. The lack of discernable p-waves and unevenly spaced QRS complexes in AF are classic findings on the ECG. Patients presenting with AF should be further evaluated with echocardiography to see if the atria are dilated or if valvular problems are responsible for the arrhythmia. A social history should be taken, and thyroid function tests should be obtained to rule out hyperthyroidism as a possible cause.
1.15 Atrial Fibrillation 1.16 Atrial Fibrillation The first treatment goal for patients suffering from atrial fibrillation is relief from symptoms that can be
directly attributed to rapid heart rate. Additional goals include risk reduction for embolic stroke and improvement of overall cardiac function. In select patients (e.g., younger patients, those with first episode of AF) the goal is to terminate AF and restore sinus rhythm. In older adults, symptom management and the prevention stroke are often the primary goals of therapy, as these individuals are often more symptomatic and are at an increased risk for stroke simply due to increased age. 1.17 Knowledge Check Question #1
1.18 Knowledge Check Answer #1 1.19 Management of Emergent and Although most patients will be diagnosed with AF during a routine office visit, some present to the
emergency room with overt symptoms and/or complications. As such, these patients require emergent care and should be immediately converted to sinus rhythm regardless of duration of AF or prior use of anticoagulation. Please note the majority of the section on Cardiac Arrhythmias will focus on the management of hemodynamically stable, non-valvular AF. 1.20 Atrial Fibrillation Electrical cardioversion involves an electrical shock delivered through the chest wall to the heart muscle, which activates all of the cardiac muscle and conduction tissue simultaneously. The shock is synchronized with the QRS complex to avoid inducing ventricular fibrillation that can occur when a shock is delivered during ventricular repolarization on the T wave. When reentrant circuits are interrupted and the arrhythmia stops, the sinus node begins to fire again and a normal heart rhythm is restored. The procedure is painful and can be distressing for the patient. The level of sedation required for electrical cardioversion is either deep sedation or general anesthesia. Appropriate anticoagulation management around the time of cardioversion is essential for reducing thromboembolic risk. The AHA/ACC/HRS guidelines recommend electrical cardioversion to restore sinus rhythm for patients with AF or atrial flutter, in hemodynamically unstable patients, and when AF does not respond to pharmacological therapies (January et al, 2014). Electrical cardioversion is also preferred in patients with decompensated heart failure, ongoing myocardial ischemia, or hypotension. In hemodynamically stable patients with a rapid ventricular response, oral medications may be administered.
Antiarrhythmic drugs can be administered for attempted conversion of AF to sinus rhythm (pharmacological cardioversion) or to facilitate electrical cardioversion. Pharmacological cardioversion is most likely effective when initiated within 7 days after onset of an episode of AF. Pharmacological cardioversion is associated with an increased risk of developing torsades de pointes, a type of ventricular tachycardia. Despite high rates of successful electrical cardioversion (>90%) and restoration of normal sinus rhythm (El-Haija and Giudici, 2014), the long-term success rate is low. One study showed that about 70% of patients were successfully cardioverted, however this figure dropped to only 20% after six months and 15% after one year (Tabery et al, 2001). In another study, about 25% of the patients remained in sinus rhythm at one year post-cardioversion; the proportion rose to approximately one-half of patients if pharmacoprophylaxis was employed (Meurling et al, 2006). Most patients who relapse to AF the first year do so within a few weeks of cardioversion. Because of the high relapse rate, antiarrhythmics are frequently used post-cardioversion to help patients remain in sinus rhythm. 1.21 Long-Term Management of Atrial Fibrillation Rate control is desired in all patients with AF as it is the most effective means of controlling symptoms and minimizing the risk of developing additional structural changes in the heart that could precipitate a cardiomyopathy. However, rate control is not always effective and some patients do not tolerate rate control. Older adults, in particular, are more susceptible to the adverse effects (e.g., fatigue, bradycardia)
of rate control agents. Rhythm control has not been shown to be superior to rate control in terms of mortality and it is associated with a greater risk of hospitalizations and adverse effects. Older adults are particularly more susceptible to the negative effects of this approach, especially those >75 years of age. As such, rhythm control should be reserved for select patients unable to achieve symptom relief or who are intolerant to rate control. 1.22 Knowledge Check Question #2
1.23 Knowledge Check Answer #2 1.24 Antiarrhythmic Drugs The Vaughn Williams Classification categorizes antiarrhythmic agents according to their primary
mechanism of action. Clearly, it has severe limitations. When initially conceived, there were relatively few antiarrhythmic drugs and our understanding of their mechanisms was imperfect at best. We now know many antiarrhythmics are multi-channel in nature. Key agents for rate control include the Class II (beta blockers) and IV (non-dihydropyridine calcium channel blockers) agents, but amiodarone and digoxin may be added in patients unable to achieve rate control with a single agent or who cannot tolerate first-line therapies. NOTE: Verapamil and diltiazem should be avoided in patients with left ventricular dysfunction. NOTE: Digoxin and nondihydropyridine calcium channel blockers (e.g., verapamil, diltiazem) are contraindicated for many patients with Wolff-Parkinson-White syndrome (WPW). WPW is the most common of several disorders that involve an extra electrical pathway between the atria and the ventricles, which makes fast arrhythmias more likely to occur. WPW syndrome is the most common cause of paroxysmal supraventricular tachycardia, and in rare cases, results in a very fast, lifethreatening heart rate during atrial fibrillation. The usual rate-slowing drugs used in AF are not effective, and digoxin and the nondihydropyridine calcium channel blockers are contraindicated because they may increase the ventricular rate and cause ventricular fibrillation (Mitchell, 2015). Use of Class I agents (sodium channel blockers) has declined considerably in recent decades due to the discovery that these agents increase mortality in patients with existing structural heart disease (e.g., heart failure, coronary artery disease). With that said, propafenone and flecainide remain viable choices in AF patients without structural heart disease. The other Class I agents have little to no role in the management of AF. Ibutilide and dofetilide are the only pure Class III agents (potassium channel blockers) in the sense that they only block potassium channels without additional effects. Ibutilide is only available for intravenous administration and is used for pharmacological conversion. Dofetilide is safe to use in patients with structural heart disease and AF. Amiodarone and dronedarone are shotgun antiarrhythmics in that they have multi-channel effects and even have beta-blocking properties. Amiodarone is safe to use in patients with structural heart disease, whereas, dronedarone can only be used in patients with coronary artery disease who have normal left ventricular function. Sotalol is primarily a non-selective beta-blocker but it also blocks potassium channels. Like dronedarone, its use is contraindicated in patients with left ventricular dysfunction. Digoxin use has also declined in recent years as newer, more effective, agents have come to market. While digoxin can effectively reduce the heart rate, it is unable to do so during high sympathetic states (e.g., exercise). However, it is considered a reasonable choice in patients unable to achieve adequate rate control on a beta-blocker or calcium channel blocker. This is especially true in patients with AF and heart failure.
1.25 Beta Blockers Beta-blockers decrease ventricular rate by altering catecholamine-dependent channel integrity, which interferes with calcium entry. These agents may be more effective at rate control than digoxin in a patient who is exercising. Beta-blockers are considered the most effective and commonly used drugs for rate control. Esmolol, propranolol, and metoprolol tartrate are available IV and are frequently used in acute situations to more quickly improve symptoms.
1.26 Calcium Channel Blockers Non-dihydropyridine calcium channel blockers also decrease ventricular rate and can be used in the acute and chronic settings. Note that dihydropyridine calcium channel blockers (e.g., amlodipine) should not be used for rate control as these agents are more selective for the periphery and may actually cause tachycardia. Verapamil and diltiazem usually provide rate control in minutes rather than the hours it takes for digoxin to work. Diltiazem may produce fewer problems with blood pressure drops when compared to intravenous verapamil. Verapamil and diltiazem should be avoided in patients with heart failure and a reduced ejection fraction due to their negative inotropic effects; however, they may be used in patients with heart failure and a preserved ejection fraction. Also watch for drug-drug interactions as both of these agents are metabolized via CYP 3A4 pathway. Finally, remember that IV calcium given with verapamil or diltiazem can attenuate the effects of these drugs on systemic vascular resistance, which can shore up a patient with borderline low blood pressure in need of these agents.
1.27 Digoxin Digoxin is not a first-line therapy for rapid rate control in patients with AF because its onset of action is >1 hour and does not peak for about 6 hours. Digoxin is a poor choice for most patients needing rate control because it does not control the ventricular response well in higher sympathetic states (e.g., exercise). This means that it may give a beneficial resting ventricular heart rate of 80 beats per minute but during exercise it may not control the rate and this could lead to symptoms. Digoxin is best used when combined with a beta-blocker or non-dihydropyridine calcium channel blocker to provide rate control when a single agent isn t sufficient. Furthermore, digoxin is a positive inotropic agent, unlike beta-blockers and non-dihydropyridine calcium channel blockers, and as such is useful in patients with heart failure and a reduced ejection fraction. Please note the important pharmacokinetic drug interactions with digoxin. Pay particular attention to serum levels of digoxin, as toxicity is more likely to occur in older adults, patients with renal insufficiency, and those with a smaller volume of distribution (e.g., low body weight). Serum levels should be maintained <1 ng/ml as higher levels have been associated with increased mortality. When drawing serum digoxin levels, one should obtain a trough drawn at least 12 hours after the previous dose.
1.28 Knowledge Check Question #3 1.29 Knowledge Check Answer #3
1.30 Rhythm Control Strategies A rhythm control strategy includes several options: antiarrhythmic drug therapy, elective cardioversion and radiofrequency ablation. There are many considerations when determining the best rhythm control strategy. Older adults with a long-standing history of AF are less likely to achieve and maintain sinus rhythm regardless of which approach is used. These individuals are also more prone to adverse effects from antiarrhythmics and are at higher risk for complications from cardioversion and radiofrequency ablation. On the other hand, younger patients without structural heart disease and with recent-onset AF can often be treated effectively with radiofrequency ablation. Radiofrequency ablation involves inserting a catheter through a vein in the groin into the heart. The catheter includes an electrode that eradicates the tissue responsible for the irregular electrical pattern. This invasive procedure is most often considered after a patient fails at least one antiarrhythmic, but is sometimes used before trying antiarrhythmics in younger patients without structural heart disease. Although initial cure rates are very high, recurrence of AF within 3 months is relatively common but does not indicate a lack of long-term success. Antiarrhythmic drug therapy is often utilized in these instances to ensure long-term success.
1.31 Antiarrhythmic Drug Therapy Selection Safety, instead of efficacy, is the primary factor to consider when selecting an antiarrhythmic for a patient. Propafenone and flecainide are avoided in patients with left ventricular hypertrophy (LVH), coronary artery disease (CAD), or heart failure because of the increased risk of mortality observed in clinical trials. Both propafenone and flecainide are also metabolized by CYP2D6. The baseline QTc interval and renal function is an important consideration before using dofetilide and sotalol as both agents carry a significant risk of torsades de pointes. As such, patients starting on dofetilide or sotalol must be hospitalized for three days to receive telemetry and renal function monitoring. Sotalol also has non-selective beta-blocking properties, making it a less-than-ideal choice for patients with uncontrolled respiratory disease. Additionally, sotalol can worsen heart failure and should not be used in this population Amiodarone is the most efficacious antiarrhythmic for maintaining sinus rhythm but it also has several notable non-cardiac toxicities involving the eyes, central nervous system, thyroid, skin, lungs, and liver. As such, a baseline chest x-ray, thyroid and liver function panel, and eye exam is recommended, followed by an annual chest x-ray, and recheck of thyroid and liver function every 6 months. Despite this, amiodarone is a preferred choice in patients with heart failure due to its demonstrated safety in this population. Dronedarone is the only antiarrhythmic that may be initiated outside of the hospital. Compared to amiodarone, it lacks the iodine moieties responsible for the thyroid abnormalities observed with amiodarone and has a much shorter half-life. Dronedarone, however, is contraindicated in patients with permanent AF and patients with heart failure due to an observed increased risk of mortality. It is also
metabolized by CYP3A4 and is an inhibitor of p-glycoprotein (P-gp). 1.32 Ventricular Arrhythmias A ventricular arrhythmia can be caused when several cells (called an ectopic focus) in one area of the ventricles begin to pace the ventricles rather than an impulse initiated in the SA node and propagated to the ventricles. Connective tissue or scar tissue that partially walls off a group of cells in the ventricles can help set up for ventricular arrhythmias. This can happen in the post-mi patient or the patient with heart failure. In addition, hypoxia of the myocardium from angina or an acute myocardial infarction and electrolyte abnormalities can increase the risk of ventricular arrhythmia as well. Idiopathic ventricular arrhythmias can also occur in people with no discernable risk factors. If an ectopic ventricular beat only happens once or twice in a row with normal beats in between, they are called premature ventricular contractions (PVCs). PVCs may be benign; however, when a patient develops three PVCs in a row the criteria for ventricular tachycardia (VT) are met. If a string of ventricular complexes last for less than 30 seconds, this is non-sustained ventricular tachycardia; if it persists for at least 30 seconds, it is referred to as sustained ventricular tachycardia. Longer stretches of ventricular tachycardia can cause syncope, hypotension, and in the worst-case scenario, cardiac arrest. Ventricular tachycardia can also degenerate into ventricular fibrillation, which always causes cardiac arrest. Lack of pulse and severe reduction or elimination of cardiac output without cardiopulmonary resuscitation characterizes cardiac arrest.
1.33 Non-Sustained Ventricular Tachycardia A conservative approach using only beta-blockers for patients with an ejection fraction (EF) >35% is recommended because the risk of sudden death is lower than in patients with an EF <35%. With that said, most patients benefit from having an electrophysiology study performed to determine individual risk. Non-inducible VT is less concerning and most patients can simply continue their beta-blocker, although switching to amiodarone is also an option. The data suggest antiarrhythmic drug therapy is inferior to placement of an implantable cardioverterdefibrillator (ICD) for patients with inducible VT. These devices are highly effective at preventing sudden cardiac death. Despite this benefit, there are several notable concerns. An ICD is an implanted device that requires significant resources (e.g., hospital stay, costs) and nearly 70% of patients require antiarrhythmic drug therapy (amiodarone or sotalol) to reduce the number of firings and preserve battery life. Additionally, patients are at risk for infection and many become anxious in anticipation of the device firing, especially after they have experienced it.
1.34 Sustained Ventricular Tachycardia In patients who have experienced sustained ventricular tachycardia (SVT), the risk of recurrence is high and may lead to sudden cardiac death. Antiarrhythmics have been well-studied to determine their ability to have a favorable impact on electrophysiology drug testing parameters, yet that does not necessarily predict the clinical efficacy of such an approach. Although amiodarone is clearly the most effective antiarrhythmic to reduce the recurrence of SVT, the risk of life-threatening ventricular tachycardia remains high and long-term, non-cardiac toxicities are of concern. Other antiarrhythmics have been shown to be less effective and have their own issues, such as a higher risk of torsades de pointes and lack of safety in patients with structural heart disease. In light of the unfavorable use of antiarrhythmics in these patients, non-pharmacological options have been considered. For instance, idiopathic ventricular tachycardia is quite responsive to catheter ablation. Because of diminished efficacy, catheter ablation remains a second-line option for patients with cardiomyopathy or myocardial infarction. Ultimately, ICDs have demonstrated superiority over antiarrhythmic drug therapy. As such, ICDs are preferred for primary and secondary prevention of sudden cardiac death. However, the previously mentioned concerns over cost, continued need for an antiarrhythmic, risk of infection, and potential for developing anxiety are potential barriers to their use.
1.35 Knowledge Check Question #4 1.36 Knowledge Check Answer #4
1.37 QTc Prolongation and Torsade de Pointes The QT interval represents the depolarization (contraction) and repolarization (relaxation) of the ventricles on an electrocardiogram rhythm strip. The QT is affected by the heart rate because a patient that is tachycardic will have shortened QT intervals, while someone who is bradycardic will have longer QT intervals. Therefore, the corrected QT, or QTc, is used to inform clinical decision-making. A prolonged QTc is >470 msec in males and >480 msec in women, but an abnormal QTc is >500 regardless of gender. Ultimately, QTc prolongation is simply a biomarker for Torsades de Pointes (TdP) and a risk factor for sudden cardiac death. On the slide is an ECG showing TdP, which is a type of polymorphic ventricular tachycardia. It is polymorphic because there are several different shapes of the tachycardia wave. While TdP can spontaneously terminate in some cases, it can also degenerate into ventricular fibrillation and lead to sudden cardiac death. Usual signs and symptoms include tachycardia, hypotension, palpitations, dizziness, shortness of breath, and/or chest pain.
1.38 Risk Factors for Drug-Induced A QTc >500 msec is associated with a 2-3 fold higher risk for developing TdP. Additionally, each 10 msec increase in the QTc increases the risk of TdP by 6% and is thus considered clinically significant. Class I and III antiarrhythmics generally carry the highest risk for TdP. Other important drug classes known to prolong the QTc include selective serotonin reuptake inhibitors, antipsychotics, macrolides, and fluoroquinolones. A detailed discussion of all the drugs capable of prolonging the QTc interval is beyond the scope of this section. An excellent source is the website, www.crediblemeds.org, which maintains an up-to-date database that categorizes drugs into one of three classes: drugs with known risk, possible risk, or conditional risk (Woosley and Romero). Because females have a more prolonged QTc than males under normal physiological circumstances, women are more prone than men to develop torsades de pointes during administration of cardiovascular drugs that prolong cardiac repolarization (Makkar et al, 1993). Individuals with a history of myocardial infarction or left ventricular dysfunction are, of course, at high risk. The natural structural changes that can occur in the heart with age; age-related renal and hepatic impairment, which may increase the blood levels of certain agents; and electrolyte abnormalities from medications affecting potassium and magnesium (e.g., diuretics) can all increase risk in older adults. More often than not, TdP occurs because of inappropriate medication adjustment for patients with impaired renal or hepatic function, use of multiple drugs with a known risk for QTc prolongation, and/or
use of drugs known to interact with QTc-prolonging agents. Ultimately, if an equally efficacious, non-qtc-prolonging therapy exists, use it instead. If the benefit of a particular drug clearly outweighs risk, QT prolongation should not limit your decision. 1.39 Knowledge Check Question #5
1.40 Knowledge Check Answer #5
1.41 Potentially Inappropriate Medications
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