Flashcards in Chapter 274 - The Bradyarrhythmias: Disorders of the Sinoatrial Node Deck (48)
The sinoatrial node is the predominant pacemaker of the normal heart. Other cells with pacemaker properties would be responsible for a higher cardiac frequency.
True or False?
"Electrical activation of the heart normally originates in the sinoatrial (SA) node, the predominant pacemaker. Other subsidiary pacemakers in the atrioventricular (AV) node, specialized conduction system, and muscle may initiate electrical activation if the SA node is dysfunctional or supressed. Typically, subsidiary pacemakers discharge at a slower rate and, in the absence of an appropriate increase in stroke volume, may result in tissue hypoperfusion."
Explain the mollecular biology of sinoatrial cells and how these features are related to its pacemaking function. Compare their electrophysiological properties to those of the atrial and ventricular myocites.
"The action potentials in the heart are regionally heterogeneous. The action potentials in cells isolated from nodal tissue are distinct from those recorded from atrial and ventricular myocytes. The complement of ionic currents present in nodal cells result in a less negative resting membrane potential compared with atrial or ventricular myocytes. Electrical diastole in nodal cells is characterized by slow diastolic depolarization (phase 4), which generates an action potenail as the membrane voltage reaches threshold. The action potential upstrokes (phase 0) are slow compared with atrial or ventricular myocytes, being mediated by calcium rather than sodium current. Cells with properties of SA and AV nodal tissue are electrically connected to the remainder of the myocardium by cells with an electrophysiologic phenotype between that of nodal cells and that of atrial or ventricular myocytes. Cells in the SA node exhibit the most rapid phase 4 depolarization and thus are the dominant pacemakers in a normal heart."
What are the two main mechanisms that may lead to sinusal brayarrythmia?
Failure of impulse initiation or impulse conduction.
Name the main physiologic differential diagnosis of pathologic sinus bradycardia. Which group of individuals might have the the first and the latter conditions?
"SA node dysfunction may be difficult to distinguish from physiologic sinus bradycardia, particularly in the young. SA node dysfunction increases in frequency between the fifth and sixth decades of life and should be considered in patents with fatigue, exercise intolerance, or syncope and sinus bradycardia."
Specify some of the extrinsic and revesible etiologies of sinus bradycardia.
Increased vagal tone, hypoxia, hypothermia, and drugs.
Permanent pacemaking is the only reliable therapy for symptomatic bradycardia. How many patients live with a pacemaker in the United States (US) and Europe and what is the cause for its colocation?
US: 150 000 permanent pacemakers, 50% of which are due to sinoatrial dysfunction and 50% due to AV node dysfunction disease.
Europe: 150 000 permanent pacemakers, 20-30% of which are due to sinoatrial dysfunction and 70-80% due to AV node dysfunction disease.
How does one distinguish the sinus node from the other cells? Make reference to its location and typical histology.
"The SA node is composed of a cluster of small fusiform cells in the sulcus terminalis on the epicardial surface of the heart at the right atrial-superior vena caval junction, where they envelop the SA nodal artery. The SA node is structurally heterogeneous, but the central prototypic nodal cells have fewer distinct myofibrils than does the surrounding atrial myocardium, no intercalated disks visible on light microscop+y, a poorly developed sarcoplasmic reticulum, and no T-tubules. Cells in the peripheral regions of the SA node are transitional in both structure and function."
What is the usual vascularization of the sinoatrial node (SA)?
The SA nodal artery arises from either the right coronary artery in 50-60% or the left circunflex artery in 40-45% of persons.
Name the channels that are mostly regulated by beta-adrenergic stimulation or by vagal stimulation.
"ICa-L, ICa-T, and If are modualted by beta-adrenergic stimulation and IKAch by vagal stimulation, explaining the exquisite sensitivity of diastolic depolarization to autonomic nervous system activity."
How does one explain the fact that the sinoatrial (SA) node has a slow conduction and presents cell heterogeneity?
"The slow conduction within the SA node is explained by the absence of IUNa and poor electrical coupling of cells in the node, resulting from sizable amounts of interstitial tissue and a low abundance of gap junctions. The poor coupling allows for graded electrophysiologic properties within the node, with the peripheral transitional cels being silenced by electrotonic coupling to atrial myocardium."
What are the most common causes of extrinsic nodal sinus dysfunction?
"The most common causes of extrinsic SA node dysfunction are drugs and autonomic nervous system influences that suppress automaticity and/or compromise conduction."
Name all the causes for extrinsic sinus node dysfunction.
- Most common causes: drugs (such as beta blocekrs, calcium channel blockers, digoxin, ivabradine, antiarrhythmics class I and III, adenosine, clonidine and other sympatholytics, lithium carbonate, cimetidine, amitriptyline, phenotiazines, narcotics such as methadone, and pentamidine) and autonomic nervous system influences (such as carotid sinus hypersensitivity and vasovagal response);
- Other causes: hypothyroidism, sleep apnea, and conditions likely to occur in critically ill patients such as hypothermia, hypoxia, increased intracranial pressure (Cushing's response), and endotracheal suctioning via activation of the vagus nerve).
Intrinsic sinus node dysfunction is degenerative and often is characterized pathologically by fibrous replacement of the SA node or its connections to the atrium."
Name all the intrinsic causes of sinus dysfunction.
- Sick-sinus syndrome (SSS)
- Coronary artery disease (chronic and acute MI)
- Inflammatory: pericarditis, myocarditis (including viral), rheumatic heart disease, collagen vascular diseases, Lyme disease;
- Senile amyloidosis;
- Congenital heart disease: Transposition of the Great Vessels/Mustard Fontan repairs;
- Iatrogenic: radiation therapy and postsurgical;
- Chest trauma;
- Kearns-Sayre syndrome
- Myotonic dystrophy
- Friedreich's ataxia
Explain the pathophysiology of sinus bradycardia in patients with senile amyloidosis.
"Senile amyloidosis is an infiltrative disorder in patients typically in the ninth decade of life; deposition of amyloid protein in the atrial myocardium can impair SA node function."
What is the mutation associated with SSS2?
SSS2 is a tachycardia-bradycardia variant of sick-sinus syndrome (SSS). "[It] has been linked to mutations in the pacemaker current (If) subunit gene HCN4 on chromosome 15."
What is the mutation associated with SSS1?
SCN5A on chromosome 3 (mutations in the cardiac sodium channel gene).
What is the mutation associated with SSS3?
"Variants in myosin heavy chain 6 (MYH6) increase the susceptibility to SSS (SSS3)."
There are several neuromuscular diseases including Kearns-Sayre syndrome and myotonic dystrophy that might be associated with a susceptibility for conduction system and SA node involvement.
True or False?
How do you characterize Kearns-Sayre syndrome?
Ophtalmoplegia, pigmentary degeneration of the retina and cardiomyopathy."
Either SSS (Sick-sinus syndrome) and ageing are associated with fibrous tissue in the SA node. The onset of SSS may be hastened by coexisting disease, such as coronary artery disease, diabetes mellitus, hypertension, and valvular diseases and cardiomyopathies.
True or False?
What are the usual symptoms and signs of SA node dysfunction?
- Asymptomatic with ECG alterations, such as sinus bradycardia, sinus arrest and exit block, or alternating supraventricular tachydaria, usually atrial fibrillation and bradycardia;
- Symptomatic: they might be related either to tachycardir or bradycardia (especially in tachycardia-bradycardia syndrome). "tachycardia may be associated with palpitations, angina pectoris and heart failure, and bradycardia may be associated with hypotension, syncope, presyncope, fatigue, and wekaness.
- SSS characteristic feature: "In the setting of SSS, overdrive suppression of the SA node may result in prolonged pauses and syncope upon termination of the tachycardia. (...) A significant minority of patients with SSS develop signs and symptoms of heart failure that may be related to slow or fast heart rates."
- Other: "In many cases, symptoms associated with SA node dysfunction result from concomitant cardiovascular disease."
How many patients with SA node dysfunction have supraventricular tachycardia? What are the main risk factors for this situation?
"One-third to one-half of patients with SA node dysfunction developt supraventricular tachycardia, usually atrial fibrillation or atrial flutter. The incidence of persistent atrial fibrillation in patients with SA node dysfunction increases with advanced age, hypertension, diabetes mellitus, left ventricular dilation, valvular heart disease, and ventricular pacing."
Some patients with SA node dysfunction have symptomatic improvement with the onset of atrial fibrillation.
True or False?
"Remarkably, some symptomatic patientsmay experience an improvement in symptoms with the development of atrial fibrillation, presumably from an increase in their average heart rate."
Besides atrial fibrillation, name another arrhythmia associated with sinus node dysfunction and thromboembolic risk. Which patients are at greater risk and might have anticoagulation indication?
"Patients with tachycardia-bradycardia variant of SSS, similar to patients with atrial fibrillation, are at risk for thromboembolism, and those at greatest risk, including patients ≥65 years and patients with a prior history of storke, valvular heart disease, left ventricular dysfunction, or atrial enlargement, should be treatet with anticoagulants."
How many patients with SA node disease have concurrent AV conduction disease?
Up to one-fourth.
What is the natural history of SA node dysfunction? How high is the mortality rate?
"The natural history of SA node dysfunction is one of varying intensity of symptoms even in patients who present with syncope. Symptoms related to SA node dysfunction may be significant, but overall mortality usually is not compromise in the absence of other significant comorbid conditions."
Name the most common cause of tachyarrhythmia in a patient with tachycardia-bradycardia syndrome.
Define chronotropic incompetence of the SA node.
"Chronotropic incompetence is the inability to increase the heart rate in response to exercise or other stress appropriately and is defined in greater detail below."
"This is alternatively defined as failure to reach 85% of predicted maximal heart rate at peak exercise or failure to achieve a heart rate >100 beats/min with exercise or a maximal heart rate with exercise less than two standard deviations below that of an age-matched control population."
Since rest ECG has some limitations to diagnose sinoatrial node dysfunction, which other exams might be important?
"Despite the limitations of the resting ECG, longer-term recording employing Holter or event monitors may permit correlation of symptoms with the cardiac rhythm. Many contemporary event monitors may be automatically triggere to record ECG when certain programmed heart rate criteria are met. Implantable ECG monitors permit long-term recording (12-18 months) in particularly challenging patients."
Exercise testing might be useful to make the differential between chronotropic incompetence and resting bradycardia.
True or False?
How does one distinguish slow heart rates that result from either SA node dysfunction or due to high vagal tone?
"Autonomic nervous system testing is useful in diagnosing carotid sinus hypersensitivity; pauses >3s are consistent with the diagnosis but may be present in asymptomatic elderly subjects. Determining the intrinsic heart rate (IHR) may distinguish SA node dysfunction from slow heart rates that result from high vagal tone. The normal IHR after administration of 0,2mg/Kg propranolol and 0,04mg/Kg atropine is 117,2 - (0,53xage) in beats/min; a low IHR is indicative of SA disease."
The combination of an abnormal sinus node recovery time, an abnormal sinoatrial conduction time, and a low intrinsic heart rate is a sensitive and specific indicator of intrinsic SA node disease.
True or False?
What is the role of electrophysiologic testing in the study of syncope?
"Electrophysiologic testing may play a role in the assessment of syncope, particularly in the setting of structural heart disease. In this circumstance, electrophysiologic testing is used to rule out more malignant etiologies of syncope, such as ventricular tachyarrhythmias and AV conduction block. There are severel ways to assess SA node function invasively. They include the sinus node recovery time (SNRT), defined as the longest pause after cessation of overdrive pacing of the right atrium near the SA node (normal: less than 1500ms or, corrected for sinus cycle lehgt, less than 550ms), and the sinoatrial conduction time (SACT), defined as one-half the difference between the intrinsic sinus cycle lenght and a noncompensatory pause after a premature atrial stimulus (less than 125ms)."
Name all the drugs with any effect on sinus node function. Explain how do these alter the normal function.
"Beta blockers and calcium channel blockers increase sinus node recovery time (SNRT) in patients with SA node dysfunction, and antiarrhythmic drugs with class I and III action may promote SA node exit block. (...) Chronic pharmacologic therapy for sinus bradyarrhythmias is limited. Some pharmacologic agents may improve SA node function; digitalis, for example, has been shown to shorten SNRT in patients with SA node dysfunction. Isoproterenol or atropine administered IV may increase the sinus rate acutely. Theophylline has been used both acutely and chronically to increase heart rate but has liabilities when used in patients with tachycardia-bradycardia syndrome, increasing the frequency of supraventricular tachyarrhythmias, and in patients with structural heart disease."
Is there any evidence regarding the use of pacing in sinus node dysfunction?
"Currently, there is only a single randomized study of therapy for SA node dysfunction. In patients with resting heart rates less than 50 and less than 30 beats/min on a Holter monitor, patients who received dual-chamber pacemakers experienced significantly fewer syncopal episodes and had symptomatic improvement compared with patients randomized to theophylline or no treatment."
What is the relationship between sinus bradycardia and myocardial infarction (MI)?
"Sinus bradycardia is common in patients with acute inferior or posterior MI and can be exacerbated by vagal activation induced by pain or the use of drugs such as morphine. Ischemia of the SA nodal artery probably occurs in acute coronary syndromes more typically with inveolvement with the right coronary artery, and even with infarction, the effect on SA node function most often is transient."
What is the evidence regarding the use of pacemakers in patients with vasovagal syncope?
"Several randomized trials have investigated the efficacy of permanent pacing in patients with drug-refractory vasovagal syncope, with mixed results. Although initial trials suggested that patients undergoing pacemaker implantation have fewer recurrences and a longer time to recurrence of symptoms, at least one follow-up study did not confirm these results."
Explain the nomenclature used to describe the function of a pacemaker.
"Pacemaker modes and function are named using a five-letter code. The first letter indicates the chamber(s) that is paced (O, none; A, atrium; V, ventricle; D, dual; S, single), the second is the chamber(s) in which sensing occurs (O, none; A, atrium; V, ventricle; D, dual; S, single), the third is the reponse to a sensed event (O, none; I, inhibition; T, triggered; D, inhibition + triggered), the fourth refers to the programmability or rate response (R, rate responsive), and the fifth refers to the existence of antitachycardia function if present (O, none; P, antitachycardia pacing; S, shock; D, pace + shock)."
Name the available modern pacing rate sensors.
Activity or motion, minute ventilation, or QT interval.
Is there any acute or chronic complication regarding pacemaker colocation? Which ones?
"Rare, but possible, acute complications of transvenous pacemaker implantation include infection, hematoma, pneumothorax, cardiac perforation, diaphragmatic/phrenic nerve stimulation, and lead dislodgment. Limitations of chronic pacemaker therapy include infection, erosion, lead failure, and abnormalities resulting from inappropriate programming or interaction with patient's native electrical cardiac function. Rotation of the pacemaker pulse generator in its subcutaneous pocket, either intentionally or inadvertently, often referred to as "twiddler's syndrome", can wrap the leads around the generator and produce dislodgment with failure to sense or pace the heart. The small size and light weight of contemporary pacemakers make this a rare complication."
Other complications include pacemaker syndrome.
How do you characterize pacemaker syndrome?
"Complications stemming from chronic cardiac pacing also result from disturbances in atrioventricular synchrony and/or left ventricular mechanical synchrony. Pacing modes that interrupt or fail to restore atrioventricular synchrony may lead to a constellation of signs and symptoms, collectively referred to as pacemaker syndrome, that include neck pulsation, fatigue, palpitations, cough, confusion, exterional dyspnea, dizziness, syncope, elevation in jugular venous pressure, canon A waves, and stigmata of congestive heart failure, including edema, rales, and a third heart sound."
What is the pathophysiollogy of congestive heart failure due to right ventricular pacing?
"Right ventricular apical pacing can induce dyssynchronous activation of the left ventricle, leading to compromised left ventricular systolic function, mitral valve regurgitation, and the previously mentioned stigmata of congestive heart failure. Maintenance of AV synchrony can mimize the sequelae of pacemaker syndrome. Selection of pacing modes that minimize unnecessary ventricular pacing or implantation of a device capable of right and left ventricular pacing (biventricular pacing) can help minimize the deleterious consequences of pacing-induced mechanical dyssynchrony at the ventricular level."
What are the class I indications for pacing?
- SA node dysfunction with symptomatic bradycardia or sinus pause
- Symptomatic SA node dysfunction as a result of essential long-term drug therapy with no acceptable alternatives
- Symptomatic chronotropic incompetence
- Atrial fibrillation with bradycardia and pauses >5s
What are the class IIa indications for pacing?
- SA node dysfunction with heart rates less than 40beats/min without a clear and consistent relantionship between bradycardia and symptoms
- SA node dysfunction with heart rates less than 40beats/min on an essential long-term drug therapy with no acceptable alternatives, without a clear and consistent relantionship between bradycardia and symptoms
- Syncope of unknown origin when major abnormalities of SA node dysfunction are discovered or provoked by electrophysiologic testing
What are the class IIb indications for pacing?
- Mildly sympatomatic patients with waking chronic heart rates less than 40beats/min
Which patients with SA node dysfunction do not benefit from pacing and its use might even be harfmul? (class III)
- SA node dysfunction in asymptomatic patients, even those with heart rates less than 40beats/min
- SA node dysfuncion in which symptoms suggestive of bradycardia are not associated with a slow heart rate
- SA node dysfunction with symptomatic bradycardia due to nonessential drug therapy