Sick Sinus Syndrome in a 97 year old femaleGAFFUD, Prima Bianca; GASPAR, Irish Vanessa; GO, Crystal Karen; GO, Stephanie; GUILLERMO, Christine; IGNACIO, Joy Celyn;

JAQUILMO, Jaquelyn; LANDICHO, Marie Angelica; LIABRES, Guillermo VictorinoUniversity of Sto. Tomas Hospital, Espana, Manila

October 14, 2010

IntroductionThe term "sick sinus syndrome" was first used by Lown in 1967 to describe the sluggish return of sinoatrial (SA) nodal

activity in some patients following DC electroversion. The term was later applied to a clinical syndrome characterized by chronic SA nodal dysfunction, a sluggish or absent SA nodal pacemaker after DC electroversion, frequently depressed escape pacemakers, and AV nodal conduction disturbances. Another set of manifestations included alternating bradycardia and supraventricular tachycardia (the bradycardia-tachycardia syndrome), commonly with underlying atrial fibrillation (AF) or atrial flutter; these findings were associated with SA nodal dysfunction and, following termination of the tachycardia, severe SA nodal depression in some patients

Case ReportThis is a case of MB, a 97 year old female from Bulacan admitted last October 1, 2010 with a chief complaint of

dizziness. Patient is a known hypertensive since 2000; she is maintained on losartan + hydrochlorthiazide (Combivar) 50 mg/tab 1 tab OD and has been compliant.

8 days prior to admission, the patient experienced dizziness while going inside their hosue. The maid then saw her lying on the ground in a supine position, groaning; the nature of the fall was not known to anyone in the house. Patient claims that there was no loss of consciousness.

1 day after, the patient experienced pain in her right shoulder. Her daughter noticed swelling and bruises all over the right shoulder and arm; she was then brought to Philippine Orthopedic Hospital. X-ray was done which revealed an oblique fracture and a displaced right proximal humerus. Application of cast was done and patient was discharged with take home medications of celecoxib (celebrex) 500mg/tab 1 tablet twice a day as needed for pain. They were instructed to follow-up after 2 weeks.

1 day later, her daughter noticed appearance of bruises over the patient’s chest. The pain over the affected area was noted be temporary relieved by celecoxib. She also noticed that the patient was gradually losing her appetite and experienced easy fatigability and weakness which rendered the patient non-ambulatory since then.

3 days prior to admission, her daughter noticed yellow discoloration of the skin of the patient. Patient did not complain of abdominal pain and change in the color of stools. However, there was noted tea colored urine.

1 day after, the patient became agitated because of the pain which caused her to forcibly remove the bandage of the cast.

She was rushed to Philippine Orthopedic Hospital a day later where her arm was placed in a cast again. Blood work-up revealed anemia and prolonged prothrombin time; Urinalysis revealed pyuria and bacteriuria; ECG results showed marked sinus bradycardia. Due to lack of facilities, patient was referred to our institution for further management and evaluation, hence this admission.

Physical exam on admission: conscious, lethargic, incoherent, not in cardiorespiratory distress, BP: 140/80 mmHg; HR: 60/bpm, regular; RR 29/cpm; Temp 36.40C, Warm moist skin, non jaundice, (+) hyperpigmented patches over the extremities, back and chest; (+) pustules scattered at the neck and face; (+) jaundice; (+) absence of right eye; Left eye: pink palpebral conjunctivae, icteric sclera, pupils 2-3 RTL, (+) ROR; nasal septum midline, turbinates not congested, no nasal discharge, no alar flaring; moist buccal mucosa, nonhyperemic posterior pharyngeal wall, tonsils not enlarged; supple neck, midline trachea, neck veins not distended, no anterior neck mass, no cervical lymphadenopathies; (+) hyperpigmented all over the chest, symmetrical chest expansion, equal tactile fremiti on both lung fields, clear breath sounds; adynamic precordium, no heaves, lifts, thrills, PMI 6th LICS AAL S2 louder at base, S1 louder at the apex, (-) murmur; abdomen globular, flabby, no visible pulsations, normoactive bowel sounds, (-) shifting dullness, liver span 7cm MC, no masses, (+) tenderness on the right flank area, traubes space not obliterated; (+) limitation on range of motion, (+) cast/ splint in place on the right upper extremity, no cyanosis, no clubbing, pulses are full and equal, no leg edema.

Neurologic Examination: Awake, follows only certain commands, GCS 10(E3V2M5); pupil(L) 2-3 mm ERTL, EOM intact, V1 V2 V3 intact, no facial asymmetry, can raise eyebrow, frown, puff cheeks, can smile; slight hearing deficit, can shrug shoulders, can turn head against resistance, uvula midline, and tongue midline on protrusion; MMT and sensory deficit cannot assess due to patients uncooperativeness; DTRs ++ on all extremities except at the right upper extremities; (-) Babinski sign and nuchal rigidity

The admitting impression was ASHD, CAD, left ventricular hypertrophy Sinus bradycardia, t/c sinus node disease, not in failure, Class III-C, hemolytic anemia, probably secondary to sepsis, rule out urinary tract infection, multiple fractures of the right humerus ribs, pelvis, to consider electrolyte imbalance probably secondary to diuretic use (thiazide). She was then referred to Nephrology, Hematology and Orthopedic surgery for further management and evaluation.

To address the sinus node disease, 24 hour Holter monitoring was done and results showed predominantly sinus bradycardia with an average heart rate of 41 beats per minue, minimum heart rate of 32 beats per minute, and maximum heart rate of 74 beats per minute. There were episodes of sinus pauses with a longest R-R interval of 1.94 seconds. There were intermittent junctional escape rhythms noted. There were occasional premature atrial complexes occurring singly, trigeminy, and quadrigeminy. There were occasional isolate premature ventricular complexes. There were no reported symptoms.Conclusion: Predominantly sinus bradycardia with occasional sinus pauses, intermittent junctional escape rhythm, occasional premature atrial complexes, occasional premature ventricular complexes, no reported symptomsm impaired chronotropic response. Findings were suggestive of sinus node dysfunction.

The patient was then referred to electrophysiology studies where she was evaluated and assessed with the need for permanent pacemaker insertion. The family was appraised about permanent pacemaker insertion but decided to defer the said procedure. The patient was patient underwent 2D Echocardiogram studies but had poor echo window. However, she was assessed to have normal left ventricle and good wall motion and contractility and estimated Ejection fraction of 62%, normal right atrium, dilated left atrium NEOT.

EtiologyThe most common cause of sick sinus syndrome is replacement of sinus node by fibrosis tissue. This can be

accompanied by degeneration and fibrosis of other parts of the conduction system like the AV node (Thery et al, 1977). The onset of SSS may be hastened by co-morbidities including CAD, diabetes mellitus, hypertension, valvular diseases and cardiomyopathies.

Alternating bradycardia and atrial tachyarrhythmia occur in over 50% of cases of SSS(Lamas et al, 2002). Atrial fibrillation is the most common atrial tachyarrhythmia and prolonged symptomatic pauses can occur after AF.

There is controversy regarding disease of the SA nodal artery. Some have suggested that CAD is a major cause while others have seen a patent artery in SSS. A correlative study of coronary artery anatomy and electrophysiologic testing found a correlation between the frequency of an abnormal intrinsic heart rate and the degree of narrowing of the SA nodal artery in patients with an acute myocardial infarction: the intrinsic heart rate was abnormal in almost all patients with more than a 75 percent narrowing, but only about 33 percent with less than 50 percent narrowing (Alboni et al, 1991).

In children, SSS is seen with congenital and acquired heart diseases particularly after corrective heart surgery. In one study, the causes of sinus node dysfunction were inappropriate bradycardia, sinus arrest, and sinoatrial exit block.

Familial sick sinus syndrome is rare and the autosomal recessive type is associated with mutations in the cardiac sodium channel gene SCN5A on chromosome 3 which is responsible for the atrial inexcitablility. Autosomal dominant sinus node dysfunction in conjunction with supaventricular tachycardia has been linked with mutations in the pacemaker current (I f) subunit gene HCN4 on chromosome 15.

The sick sinus syndrome is less often caused by a variety of other diseases: infiltrative (amyloidosis, scleroderma), epicardial and pericardial disease, inflammatory diseases (SLE, RA, RHD), drugs and trauma.

Diagnosis

SA node dysfunction most commonly diagnosed clinically or by electrocardiographic studies. Symptoms should be correlated to findings in long-term recordings.

Long-term ECG recording using Holter or event monitors play a central role in the diagnosis and management of SA node dysfunction.

Autonomic nervous system testing is useful in identifying carotid sinus hypersensitivity. Diagnosis is made when pauses >3s are found. Determining the intrinsic heart rate (IHR) helps differentiate those with intrinsic causes from those with extrinsic causes of SA node disease. A low IHR suggests intrinsic SA node dysfunction while a normal IHR suggests extrinsic causes.

Electrophysiologic testing is used in the assessment of patients with presumed SA node disease as well as in the evaluation of syncope. It can be used to rule out more malignant etiologies of syncope such as ventricular tacharryhythmias and AV conduction block. The following parameters assess SA node function:

Sinus node recovery time (SNRT) – the longest pause after cessation of overdrive pacing of the right atrium near the SA node (normal: <1500 ms)

Sinatrial conduction time (SACT) – one-half the difference between the intrinsic sinus cycle length and a noncompensatory pause after a premature atrial stimulus (normal: <125 ms)

An abnormal SNRT, SACT, and a low IHR is sensitive and specific for intrinsic SA node disease.

ECG tracing (October 1, 2010): Sinus bradycardia

Pathogenesis of Sick Sinus Syndrome (Sinus node dysfunction)

Before discussing the pathology behind this disease entity, it is important to display the normal mechanics of the electrical conductivity and conduction system of the heart. The heart is made up of four chambers — two upper chambers (atria) and two lower chambers (ventricles). And its rhythm is normally controlled by the sinoatrial node (SA node/ sinus node ) which is an area of specialized cells located in the right atrium. This natural pacemaker produces the electrical impulses that trigger each heartbeat. From the sinus node, electrical impulses travel across the atria to the ventricles, causing them to contract and pump blood out to your lungs and body. A normal sinus node paces a resting heart between 60 and 100 beats a minute. The normal electrical conduction of the heart allows electrical propagation to be transmitted from the Sinoatrial Node through both atria and forward to the Atrioventricular Node. Normal/baseline physiology allows further propagation from the AV node to the Ventricle or Purkinje Fibers and respective bundle branches and subdivisions/fascicles. Both the SA and AV nodes stimulate the Myocardium. Time ordered stimulation of the myocardium allows efficient contraction of all four chambers of the heart, thereby allowing selective blood perfusion through both the lungs and systemic circulation.

Conduction pathway of the myocardium

Signals arising in the SA node (propagating to the left atrium via Bachmann's bundle) stimulate the atria to contract. In parallel, action potentials travel to the AV node via internodal pathways. After a delay, the stimulus is conducted through the bundle of His to the bundle branches and then to the purkinje fibers and the endocardium at the apex of the heart, then finally to the ventricular myocardium.

Microscopically, the wave of depolarization propagates to adjacent cells via gap junctions located on the intercalated disk. The heart is a functional syncytium. In a functional syncytium, electrical impulses propagate freely between cells in every direction, so that the myocardium functions as a single contractile unit. This property allows rapid, synchronous depolarization of the myocardium. While normally advantageous, this property can be detrimental as it potentially allows the propagation of incorrect electrical signals. These gap junctions can close to isolate damaged or dying tissue, as in a myocardial infarction.

Sick sinus syndrome is a type of cardiac arrhythmia. In corollary, sick sinus syndrome is an affectation of the heart’s pacemaker, the sinus node which in turn results in a combined presentation of arrhythmias. It may result in many abnormal heart rhythms including sinus arrest, sinus node exit block, sinus bradycardia, and other types of bradycardia. It may also present with tachycardia or a combination of both.

Pathology

The pathology of Sick sinus syndrome lies in the pacemaker of the heart. This involves abnormalities in sinus node impulse formation and propagation, which are often accompanied with similar abnormalities in the atrium and the conduction system in the heart. Together, these abnormalities may result in inappropriately slow ventricular rates and long pauses at rest or during various stresses. Thus, any modality (physical, chemical, etc) that may cause injury to the conduction system of the heart may lead to the pathology of sick sinus syndrome.

Recent studies suggest that scarring in the myocardial tissue and conduction system of the heart leads to the pathology of Sick sinus syndrome. Cardiac surgery, infarction, degenerative changes with aging, etc may induce damage in the myocardium leading to scarring and remodeling of the cardiac tissue. This leads to alterations in impulse propagations in the conduction system of the heart. Other journals reviewed by our group suggest that coronary artery disease, high blood pressure, and aortic and mitral valve diseases may be associated with sick sinus syndrome, although this association may only be incidental. A case report in 2007 by the American Journal of Critical Care (by Lemberg and Keller) showed an iatrogenic cause of sick sinus syndrome. To date, the exact cause leading to sick sinus syndrome is still undetermined, however, the previously mentioned processes are possible pathophysiologies leading to the development of sick sinus syndrome.

Management

Treatment of SSS is directed at symptoms such as lightheadedness, presyncope, syncope, and, less often, dyspnea on exertion or worsening angina. In addition, patients with tachycardia-bradycardia syndrome may present with palpitations.

In order to treat patients appropriately, it is important to correlate symptoms with bradycardia. Some patients have episodic symptoms suggestive of an arrhythmia (eg, lightheadedness or palpitations), but are found to have a relatively normal heart rhythm during an episode. Therapy directed at an arrhythmia (eg, a pacemaker) will not alleviate such symptoms. Due to the intermittent nature of symptomatic arrhythmias, ambulatory monitoring or an event recorder is often required to establish this correlation.

Treatment of SSS should begin with a search for remediable causes of sinoatrial (SA) nodal depression, such as drugs (eg, beta blockers, calcium channel blockers, digoxin, sympathetic blockers, lithium, cimetidine, and antiarrhythmic agents), ischemia, and autonomic imbalance. Specific treatment for the control of symptomatic SSS usually involves the implantation of a pacemaker. Medications may be helpful in selected cases, but are rarely used for this purpose.

Symptomatic SSS is usually treated with a pacemaker, and SSS accounts for over one-half of pacemakers implanted. The most common indication for pacemaker placement is a documented correlation between symptoms and sinus bradycardia or sinus pauses (table 1). These symptoms are well controlled with pacing, although survival is probably not improved.

ACC/AHA/HRS: Indications for permanent pacing in sinus node dysfunction (Table 1)Class I - There is evidence and/or general agreement that permanent pacing is indicated in patients with sinus node dysfunction in the following settings:• Documented symptomatic bradycardia, including frequent sinus pauses that produce symptoms. (Level of Evidence: C)• Symptomatic chronotropic incompetence. (Level of Evidence: C)• Symptomatic sinus bradycardia that results from required drug therapy for medical conditions. (Level of Evidence: C)Class IIa - The weight of evidence or opinion is in favor of the usefulness of permanent pacing in patients with sinus node dysfunction in the following settings:• Heart rate <40 beats per minute when a clear association between significant symptoms consistent with bradycardia and the actual presence of bradycardia has not been documented. (Level of Evidence: C) • Syncope of unexplained origin when clinically significant abnormalities of sinus node function are discovered or provoked in electrophysiological studies. (Level of Evidence: C) Class IIb - The evidence or opinion is less well established that permanent pacing in sinus node dysfunction is beneficial in the following setting: • Minimally symptomatic patients with chronic heart rate <40 beats per minute while awake. (Level of Evidence: C) Class III - There is evidence that permanent pacing in sinus node dysfunction is not useful and may be harmful in the following settings: • Asymptomatic patients. (Level of Evidence: C) • Patients for whom the symptoms suggestive of bradycardia have been clearly documented to occur in the absence of bradycardia. (Level of Evidence: C) • Symptomatic bradycardia due to nonessential drug therapy. (Level of Evidence: C)

Adapted from Epstein, AE, DiMarco, JP, Ellenbogen, KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

Not infrequently, a symptomatic bradyarrhythmia is induced by drugs that are necessary for the treatment of concurrent atrial and ventricular tachyarrhythmias. Drug-induced bradycardia due to a necessary medication is a reasonable indication for insertion of a pacemaker.

The five-position pacemaker code with the positions are as follows. Only the first three or four positions are typically used. Position I — Chamber or chambers paced (ie, atrium [A], ventricle [V], both [D, for dual]). Position II — Chamber or chambers sensed. Position III — Mode of response. I indicates that a sensed spontaneous beat inhibits the pacemaker. D indicates a

dual response and is restricted to dual chamber (atrium and ventricle) systems: an event sensed in the atrium inhibits the atrial output but triggers a ventricular output. If a native ventricular signal or R wave is sensed, it will inhibit the ventricular output.

Position IV — Programmability and rate modulation. An R is the only indicator commonly used in position IV and indicates a rate-modulated or rate-adaptive pacemaker. Such pacemakers incorporate a sensor to modulate the heart rate, increasing the pacing rate during exercise in response to vibration, minute ventilation, temperature, oxygen saturation, or other stimuli.

Position V — Antitachycardia functions (rarely used).Selection of the type of pacemaker and appropriate programming for a specific patient depends upon the presence or

absence of AV conduction abnormalities, the presence or absence of atrial arrhythmias, the desire to maintain AV synchrony, and the need for rate-responsiveness (algorithm 1).

Selection of pacemaker systems for patients with sinus node dysfunction

Reproduced with permission from: Epstein, AE, DiMarco, JP, Ellenbogen, KA, et al. ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2008; 51(21):e1-e62.

Physiologic pacing refers to pacing systems that most closely approximate normal cardiac behavior. The term usually refers to systems that maintain AV synchrony (eg, AAI or DDD systems, in contrast to VVI systems), but has also been applied to rate-responsive pacemakers. Promoting intrinsic AV conduction and minimizing right ventricular pacing is considered a very important component of physiologic pacing. Physiologic pacing with AAI or DDD pacemakers can improve a number of outcomes compared to VVI pacing. These include: Reduced incidence of AF, improved hemodynamics and avoidance of pacemaker syndrome.

Management options for symptomatic patientsAlternative approaches and additional issues have been considered, including pharmacologic therapy for sinus node

dysfunction, anticoagulation to reduce the risk of thromboembolism, and the ablation of tachyarrhythmias in patients with tachy-brady syndrome. Although each of these treatments may be beneficial in selected patients, none is a standard component of therapy in all patients or an adequate substitute for pacemakers in patients with symptomatic SSS.

Drugs may be required for the treatment of associated supraventricular and ventricular arrhythmias and a number of cardiovascular medications can further suppress a sick SA node or unmask previously latent SA nodal dysfunction.

Anticoagulation — thromboembolism is not uncommon in patients with SSS, particularly those with the bradycardia-tachycardia syndrome and AF. Thromboembolism is most likely related to the associated tachyarrhythmia. Anticoagulants are only considered if there are reasons to suspect episodes of AF are occurring.

Ablation to prevent AF — Alternating bradycardia and atrial tachyarrhythmias occur in over 50 percent of cases of SSS. AF is the most common atrial tachyarrhythmia.

In some patients with tachy-brady syndrome, the tachyarrhythmia may cause sinus node remodeling that worsens the bradycardia or results in prolonged, symptomatic pauses at the time of spontaneous conversion from AF to sinus rhythm. In such patients, radiofrequency ablation (RFA) to prevent recurrence of AF can reverse sinus node remodeling as evidenced by a reduction in sinus node recovery time, increases in the mean and maximal heart rates, and the resolution of symptoms attributable to bradycardia, possibly avoiding the need for pacemaker implantation.

Summary and RecommendationsThe following is a summary of the recommended approach to the patient with sinus node dysfunction.Choice of pacemaker — In patients with SSS who require pacing:

• It is recommended that pacemakers that maintain AV synchrony. For patients with normal AV conduction, either an AAI or a dual chamber pacemaker may be used. For patients with baseline abnormalities in AV conduction, a dual chamber pacemaker should be used.A number of additional pacemaker features may be useful in selected patients:

• Pacemakers with "rate drop" programming capabilities may benefit some patients with neurocardiogenic syncope. This would include dual-chamber pacemakers that minimize RV pacing and therefore minimize dyssynchrony.

• Rate responsive programming is particularly helpful in patients with SSS and chronotropic insufficiency and exertional symptoms.

• Mode switching is important in patients with SSS who have paroxysmal atrial tachyarrhythmias.• Pacemakers with managed ventricular pacing capability may be beneficial in patients with SSS and PR prolongation

or intermittent AV block.

Follow-upOnce a pacemaker has been selected and implanted, there are three major issues that need to be considered during

patient follow-up: 1) Because ventricular pacing can induce dyssynchrony with adverse effects on ventricular function, patients should

be observed for evidence of heart failure. The development of otherwise unexplained symptoms of heart failure may reflect the adverse effects of ventricular pacing; such patients may benefit from efforts to reduce the frequency of ventricular pacing (eg, increased programmed AV delay or managed ventricular pacing), or from upgrading the device to a biventricular pacemaker.2) In patients with an AAI pacemaker, monitoring for progression to high degrees of AV block is essential as the reported rate varies from 0.6 to as high as 3 percent per year. 3) Due to the thromboembolic risks associated with unrecognized AF, patients should be observed for the development of atrial arrhythmias.

The incidence of sudden cardiac death in patients with SND is very low. The mortality in patients with SND is primarily determined by underlying heart diseases. The patients with tachy-brady syndrome have a worse prognosis than patients with isolated SND. Pacemaker therapy does not appear to affect survival in patients with SND and is, therefore, used primarily for alleviation of symptoms.

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Thery, C, Gosselin, B, Lekieffre, J, Warembourg, H. Pathology of the sinoatrial node. Correlations with electrocardiographic findings in 111 patients. Am Heart J 1977; 93:735.

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Lamas, GA, Lee, KL, Sweeney, MO, et al. Ventricular pacing or dual-chamber pacing for sinus-node dysfunction. N Engl J Med 2002; 346:1854.

Alboni, P, Baggioni, GF, Scarfo, S, et al. Role of sinus node artery disease in sick sinus syndrome in inferior wall acute myocardial infarction. Am J Cardiol 1991; 67:1180.

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