Incidence and Predictors of Syncope in Paced Patients with Sick Sinus Syndrome ELENA B. SGARBOSSA, SERGIO L. PINSKI, FREDRICK J. JAEGER, RIGHARD G. TROHMAN, and JAMES D. MALONEY From the Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio
SGARBOSSA, E.B., ET AL,: Incidence and Predictors of Syncope in Paced Patients with Sick Sinus Syndrome. In spite of a normal pacemaker/unction, syncope stilJ occurs in some patients with sick sinus syndrome fSSS). Causes often remain unknown. To identify predictors and etiologies of this bothersome symptom, we studied 507 patients who received atriaJ, ventricular, and duaJ-chamber pacemakers for SSS. During a mean foiJow-up of 62 ± 38 months, actuarial incidence of syncope was 3% at 1 year, 8% at 5 years, and 13% at 10 years. Causes were vasovagaJ (18%), orthostatic hypotension (25.5%), rapid atrial tachyarrhythmias fn.5%), venfricuJar tachycardia (5%), acute myacardial ischemia (2.5%), and pacemaker/Jead malfunction {6.5%}. In 13 patients (29.5%), syncope remained unexplained. The only preimplanf predictor for syncope was syncope as primary indication for pacemaker implant. Electrocardiographic correlation with bradycardia was not a predictor of relief of syncope during the follow-up. In conclusion: (1) syncope in paced patients with SSS has multiple etiologies and may be muJtifactorial; (2) the only predictor of syncope after pacemaker implant is the occurrence of preimplant syncope as the main indication for pacing; (3) extensive Holter monitoring is not usefuJ to document bradycardic origin of syncope nor to predict its recurrence; (4) SSS probably overlaps with other entities such as autonomic dysfunction, vasovagaJ syncope, carotid sinus hypersensitivity, and venous pooling, which wouJd provide an expJanation for recurrent syncope in patients with normaJ pacemaker function. (PACE, Vol. 15, November, Part II 3 992) pacing, sick sinus syndrome, syncope
Introduction Syncope is a common clinical problem, accounting for 3% of emergency room visits and 6% of medical admissions to general hospitals.^'^ It is particularly common in the elderly, with an annual incidence of 6% to 7%^'* and carries considerable morbidity from trauma. The diagnosis of sick sinus syndrome (SSS) can frequently be made in elderly patients with syncope, usually mandating permanent pacing. Chronic pacing is effective in suppressing recurrent syncope in most patients with SSS.^ However, syncope may recur after pacemaker implantation or, if absent before, may develop de novo. Although syncope in paced patients has been often attributed to pacemaker mal-
function or ventricular arrhythmias, a recent report on patients with ventricular pacemakers concluded that pacemaker dysfunction was not a major cause of syncopal episodes, and that these are most often of vasovagal origin.^ Most likely, etiologies are multiple. To our knowledge, no large study has analyzed the actuarial incidence and predictors of syncope in paced patients with SSS, nor assessed the possible role of different pacing modalities. In the present study, we summarize the data obtained through a long-term follow-up on a population with atrial, ventricular, and dual-chamber pacemakers. Methods Study Patients
Address for reprints: James D. Maloney, M.D., Dept. of Cardiology, Desk F 15, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, Fax: (216) 444-0456,
PACE, Vol. 15
Between January 1980 and December 1989, we implanted an initial pacemaker in 507 adult
November, Part II 1992
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SGARBOSSA, ET AL.
patients (age more than 18 years) with SSS. SSS was defined by the presence of inappropriate, persistent sinus bradycardia [rate < 50 beats/min), sinus pauses longer than 3 seconds, or sinoatriai block. Patients in permanent atrial fibrillation at time of implant or with complete atrioventricular (AV) block or type II second degree AV block were excluded from the study. Baseline demographic variables as well as cardiac and concomitant diseases, electrocardiographic findings and pacing modes were analyzed (Table I). All patients were symptomatic, required bradycardia-producing drugs for treatment of tachyarrhythmias, or both. Syncope was the most common preimplant symptom, accounting for 39% of all indications for pacing (Fig. 1). Documentation of symptomatic hradycardia, e.g., its simultaneous occurrence with syncope, was consid-
Table I. Patient Characteristics
Need for Drugs 10% Near Syncope 9%
Syncope 39%
Figure 1. Specific indications for pacing.
ered desirable but not imperative for pacemaker implantation. During the second half of the study period, tilt-table testing was performed where indicated as part of the work-up of patients with syncope/ Pacing modes selected are depicted in Figure 2. Follow-Up
Clinical variables Age, years Maie/Female No structural heart disease
66 ± 12 308/199 211 (42%)
Structural heart disease* Coronary artery disease Valvular heart disease Mitrai valve prolapse Cardiomyopathy
217 (43%) 61 (12%) 35 (7%) 35 (7%)
Concomitant diseases Hypertensicn Diabetes Cerebrovascular disease Peripheral vascular disease
217 (43%) 72 (14%) 101 (20%) 45 (9%)
Electrocardiographic findings Bundle branch block Prolonged sinus pauses (more than 5
Fatigue 4%
77 (15%) 52 (10%)
The outcome end point for the study was the occurrence of syncope after pacemaker implant. Near-syncope was not analyzed. Patients were followed-up for a mean of 62 ± 38 months. Followup began on the date of pacemaker implant, and ended on the date of the first episode of syncope, the patient's death, or the end of the study. Symptoms and survival status were ascertained through review of medical records, questionnaires completed hy the patient's private physician, and telephonic interviews with the patients or their families. Follow-up was complete in 98.5% of the patients.
Dual-chamber 376 74%
sec) Paroxysmal atrial arrhythmia Complex ventricular arrhythmia
375 (74%) 162 (32%)
Documentation of symptomatic bradycardia among patients with syncope
78 (15%) Ventricuiar 112 22%
' Some patients had more than one cardiac disease.
2056
Atrial 19 4%
November, Part II 1992
Figure 2. Pacing modes selected.
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SYNCOPE IN SICK SINUS SYNDROME
tion for pacing was the only predictor of postimplant syncope [P < 0.001; hazard ratio = 3.9; 95% confidence interval = 2.0 to 7.4). Neither the clinical variables analyzed nor the pacing modalities were predictors of syncope during the follow-up. Among patients with preimplant syncope, recurrence of this symptom did not differ significantly between those with and without documentation of hradycardia or pauses as cause of preimplant syncope (P = 0.3). Causes of syncope, results of eventual tilt-table tests, pacing mode, and presence of ECC correlation with syncope are listed in Tahle II.
0.500
O
0.000
60
100
80
120
MONTHS
Figure 3. Actuarial incidence of syncope.
Discussion Statistical Analysis Continuous variables are presented as mean ± 1 SD. Actuarial curves for the incidence of syncope for each analyzed variahle were calculated with the method of Kaplan and Meier and compared hy means of the log-rank test. A P vaiue < 0.05 was considered significant.
Results During follow-up, 44 out of 507 paced patients (8.6%) had recurrence or syncope de novo. Actuarial incidence of syncope was 3% at 1 year, 8% at 5 years and 13% at 10 years (Fig. 3). This proportion markedly increases to 20% for the suhgroup of patients whose indication for pacing was syncope (Fig. 4). Syncope as primary indica-
iCOPE
0.500 • - - No PfBvkxjs Syncopo 13/311 Pr«vtous Syncope 31/196 0.375
in IL
NCI DENCE
O
0.250
0.125
0.000
'^--'•---T
40
60
80
100
120
140
MONTHS
Figure 4. Actuarial incidence of syncope in patients with and without syncope as indication for pacemaker implantation.
PACE, Vol. 15
Syncope is not an uncommon event in paced patients with SSS. Our 10-year actuarial incidence of 9% is similar to that in a recent report.^ As in other populations, syncope can be secondary to a myriad of etiologies.^ Vasovagal and carotid sinus syncope, orthostatic hypotension, drugs, ventricular and supraventricular tachyarrhythmias all need to be considered. Additional potential causes in paced patients are pacemaker malfunction and the pacemaker syndrome.^" Through extensive work-up, the mechanism of syncope could he explained in 71% of our patients. In previous series, the etiology of syncope in paced patients remained unknown in as many as 66% of cases. ^ ^ Orthostatic hypotension was the most frequent cause of syncope in our population. Few patients had full evidence of autonomic insufficiency. In others, orthostatic hypotension was secondary to relative hypovolemia, venous blood pooling, and/or drugs. Similarly, in a prospective study of unpaced patients with syncope, orthostatic hypotension was common in patients in whom an alternative cause was initially assigned, representing 31% of the cases.^^ Vasovagal syncope was the second most frequent etiology in our patients, accounting for 18% of the cases. Orthostatic hypotension and vasovagal syncope can be diagnosed hy the tilt-table test. However, there are no "gold standards" for diagnosing the cause of syncope of unknown etiology.^^ Only two of our patients had baseline tilttahle testing. One with subsequent syncope due to orthostatic hypotension had a normal study, whereas another one with vasovagal syncope during follow-up had a positive test.
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Table II Patients with Syncope During the Follov^r-Up Patient No.
1 2 3 4 5 6 7 8 9
42 74 57
M M F
M M M M F M M F
M M F M M M F
M F M F M M F F
M M F F M F M M
F F F M Ll_
42 43 44
M M
LL
40 41
Age
LL
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39
Gender
F
68 74 85 67 71 53 70 77 56 64 66 61 47 51 71 25 59 78 53 81 41 68 75 39 50 67 56 46 71 82 58 66 80 73 87 76 76 64 75 62 66
Pacing Mode
Prior Syncope
DVI AAI DDD DDD DDD DDD DDD
Y N Y N Y
DDD DVI
N
VVI VVI DVI DDD DDD VVI VVI DVI DDD DDD DDD DDD DDD VVIR DVI VVI DDD DDD DDD DVI DDDR DVI
DDD VVI VVI VVI DDD VVI DDD VVI DDD DDD AAI DDD DDD
N Y
Y Y Y Y Y Y
Y Y Y Y Y
Y Y
Y N N Y Y Y Y Y Y Y
Y Y
N N N Y
Y N N N
Y Y Y
HUT
Diuretics
Antihypertensives
Etiology
Normal NP NP
7
?
N N Y N N Y Y N ? N N N
N
Atrial Fib Exit block Ortho Hypo Unexplained Ortho Hypo Ortho Hypo Unexplained Unexplained Unexplained Ortho Hypo Unexplained Vasovagal Ortho Hypo Unexplained Vent Taohy Ortho Hypo Atrial Fib Unexplained Ortho Hypo Battery Deple Ortho Hypo Vent Tachy Vasovagal Valsa Unexplained Vasovagal Valsa Ortho Hypo Vasovagal Vasovagal Vasovagal Unexplained Atrial Fib Vasovagal Ortho Hypo Unexplained Atrial Flutter Ortho Hypo Unexplained Unexplained Unexplained Ortho Hypo Vasovagal Valsa Battery Deple Acute Ml Atrial Fib
NP NP (+) NP NP NP
NP NP Normal NP Normal NP NP NP NP (+) NP NP
NP NP NP NP
NP NP (+) NP
NP NP (+) NP
Normal Normal Normal NP NP NP NP NP NP NP NP
Y Y ? ? Y N N ? N
Y N Y
Y N N N N N N N
Y
N Y Y N Y N N ? N N Y N N ? ? Y N
N ? Y N
N Y N N N N
N N
N N Y
N N N N ?
N N
Y
Y ? N ? N
? N ? Y
Y N 9
Deple = depletion; Fib = fibrillation; HUT = head-up tilt test; Ml = myocardial intarction; NP = not performed; Ortho Hypo = orthostatic hypotension; Vasovagal Valsa = vasovagal during Valsalva maneuver; Vent Tachy = ventricular tachycardia; ? = information not available.
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SYNCOPE IN SICK SINUS SYNDROME
It should be noted that pacing that is successful in treating bradycardia-induced symptoms may not be effective in preventing syncope originated in an abrupt fall in total peripheral resistance, a common final pathway for vasovagal and orthostatic mechanisms. Conventional DDD pacing may abolish syncope due to carotid sinus hypersensitivity,^^'^^ but does not appear to prevent vasovagal syncope.^^ Recently, special AV sequential pacing modalities, including DVI pacing with a short AV delay and rate hysteresis^''and DDD pacing with a 50/100 hysteresis,'" were shown to abort vasovagal reactions in the setting of tilt-tahle testing. They appear to work by preventing marked falls in the blood pressure that follow hradycardia. Rapid atrial fibrillation and flutter caused 12% of the syncopal episodes. The pathophysiology of syncope in patients with atrial tachycardias is not fully understood. A short cycle length during the tachyarrhythmia may not be sufficient per se to account for the loss of consciousness; some patients with very rapid ventricular responses never have syncope, but palpitations or shortness of breath. An inadequate hemodynamic response to the tachycardia, similar to that of the vasovagal syncope, may be the underlying mechanism for fainting in patients with atrial tachyarrhythmias.'^ As in other studies,^-^ pacemaker malfunction was not an important cause of syncope during the follow-up. Exit block was identified in one patient with an AAI pacemaker and the system was changed for a VVI unit. Another two patients were found to have early battery depletion and their generators replaced. Pacemaker syndrome was not incriminated as the cause of syncope in any patient. However, other symptoms compatible with pacemaker syndrome mandated upgrade to a dual-chamber pacemaker in 9% of the patients with ventricular pacemakers. Mixed or vasodepressor forms of carotid sinus hypersensitivity could have hoen involved in some patients in whom the etiology of syncope remained unknown. Carotid sinus hypersensitivity was not systematically evaluated in our population prior to pacemaker implant, hut it is present in 8% of patients with SSS.^° Pacing has been shown to be unable to abolish symptoms in most patients with isolated vasodepressor or mixed response to carotid hypersensitivity.'^'^'
PACE, Vol. 15
Current joint ACC/AHA guidelines for implantation of pacemakers require the documentation of symptomatic bradycardia or pauses to qualify as a class I indication for pacing in SSS.^^ However, the lack of strict correlation between symptoms and the ECG should not preclude pacemaker implantation when felt clinically indicated.^^•^•' During Holter monitoring, the likelihood of recording a fortuitous bradyarrhythmic symptomatic event is discouragingly low.^^-^^ Electrocardiographic documentation may be feasible only in highly preselected populations undergoing very prolonged monitoring.^'^ We found a relatively low proportion (15%) of documented bradycardia as the cause of preimplant syncope, in spite of the significant number of 24-hour ambulatory Holter monitors and in-hospital telemetries [mean: 3.1 sessions per patient) available for analysis in these patients. In a subgroup of patients with SSS and paroxysmal symptoms, Lamas et al.^^ reported a documented symptomatic bradycardia in nearly 50%; however, their definition of documentation was less stringent since it included correlation with near-syncope as well. Interestingly, neither in our study nor in Lamas' did the documentation of symptomatic bradycardia prior to implant improve the likelihood of symptom relief.
Conclusions In paced patients w^ith SSS, syncope is a relatively common event, particularly when the indication for pacing is syncope. Moreover, this indication is the only predictor for recurrence during the follow-up. The search for a strict symptomECG correlation does not seem to improve the likelihood of syncope relief. Causes of these episodes remain unclear in more than 20% of patients. Vasovagal syncope and orthostatic hypotension are the most frequent mechanisms. Current pacing modalities may not be sufficient to circumvent these disorders. Tachyarrhythmias and pacemaker malfunctions are less prevalent etiologies. There is probably overlap between SSS and other entities, such as autonomic dysfunction, vasovagal syncope, carotid sinus hypersensitivity, and venous pooling, which would explain that some patients with SSS remain symptomatic in spite of normal pacemaker function.
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References 1. Day SC, Cook EF, Funkenstein H, et al. Evaluation and outcome of emergency room patients with transient loss of consciousness. Am ] Med 1982; 73:15-23. 2. Manolis AS, Linzer M, Salem D. et al. Syncope: Current diagnostic evaluation and management. Ann Int Med 1990; 112:850-863. 3. Whiteside-Yim C. Syncope in the elderly: A clinical approach. Geriatrics 1987; 42:37-41. 4. Lipsitz LA, Wei JY, Rowe JW. Syncope in an elderly, institutionalized population: Prevalence, incidence, and associated risk. Q ] Med 1985; 55: 45-54. 5. Conde CA, Leppo J, Lipski J, et al. Effectiveness of pacemaker treatment in the bradycardia-tachycardia syndrome. Am J Cardiol 1973; 32:209-214. 6. Pevlovic SU, Kocovic D, Djordjevic M, et al. The etiology of syncope in pacemaker patients. PACE 1991; 14:2086-2091. 7. Ahi-Samra F, Maloney ID, Fouad-Tarazi FM, et al. The usefulness of head-up tilt testing and hemodynamic investigations in the workup of syncope of unknown origin. PACE 1988; 11:1202-1214. 8. ]e\i6 V, Belkic K, DjordjeviiS M, et al. Survival in pacemaker patients: Prognostic factors and comparison with the general population. PACE 1992; 15:141-147. 9. laeger FI, Maloney JD, Fouad-Tarazi FM. Newer aspects in the diagnosis and management of syncope. In E Rappaport [ed.}: Cardiology Update. New York, NY, Elsevier, 1990, pp. 141-173. 10. Ahcandri C, Fouad FM, Tarazi RC, et al. Three cases of hypotension and syncope with ventricular pacing: Possible role of atrial reflexes. Am I Cardiol 1978; 42:137-142. 11. Langenfeld H, Grimm W, Maisch B, et al. Course of symptoms and spontaneous ECG in pacemaker patients: A 5-year follow-up study. PACE 1988; 11; 2198-2206. 12. Atkins D, Hanusa B, Sefcik T, et al. Syncope and orthostatic hypotension. Am I Med 1991; 91: 179-185. 13. Fitzpatrick AP, Theodorakis G, Vardas P, et al. Methodology of head-up tilt testing in patients with unexplained syncope. ] Am Coll Cardiol 1991; 17:125-130. 14. Madigan NP, Flaker GC, Curtis I, et al. Carotid sinus hypersensitivity: Beneficial effects of dualchamber pacing. Am J Cardiol 1984; 53; 1034-1040. 15. Morley CA, Perrins El, Grant P, et al. Carotid sinus syncope treated by pacing. Analysis of persistent
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16.
17. 18.
19.
20. 21.
22.
23.
24.
25.
26. 27.
symptoms and role of atrioventricular sequential pacing. Br Heart J 1982; 47:411-418. Stone IM, Bhakta RD, Lutgen J. Dual chamber sequential pacing management of sinus node dysfunction: Advantages over single-chamber pacing. Am Heart ] 1982; 104:1319-1327. Fitzpatrick A, Theodorakis G, Ahmed R, et al. Dual chamber pacing aborts vasovagal syncope induced by head-up 60° tilt. PACE 1991; 14:13-19. McGuinn WP, Wilkoff BL, Maloney JD, et al. Treatment cf autonomically-mediated syncope v\dth rapid AV sequential pacing on demand, (abstract) I Am Coll Cardiol 1991; 17:27lA. Leitch JW, Klein GJ, Yee R, et al. Syncope associated with supraventricular tachycardia: An expression of tachycardia rate or vasomotor response? Circulation 1992; 85:1064-1071. Brignole M, Menozzi C, Lolli C, et al. Pacing for carotid sinus syndrome and sick sinus syndrome. PACE 1990; 13:2071-2075. Sugrue DD, Gersh BJ, Holmes DR, et al. Symptomatic "isolated" carotid sinus hypersensitivity: Natural history and results of treatment with antichclinergic drugs or pacemaker. J Am Coll Cardiol 1986; 7:158-162. Dreifus LS, Fisch C, Criffin JC, et al. Guidelines for implantation of cardiac pacemakers and antiarrhyhmia devices. A report of the American College of Cardiology/American Heart Association Task Force on assessment of diagnostic and therapeutic cardiovascular procedures [Committee on pacemaker implantation). I Am Coll Cardiol 1991; 18; 1-13. Lamas GA, Dawley D, Splaine K, et al. Documented symptomatic bradycardia and symptom relief in patients receiving permanent pacemakers: An evaluation of the Joint AGG/AHA Guidelines. PAGE 1988; 11:1098-1104. Goldschlager N. Underlying assumptions in evaluating "symptomatic bradycardia" [or. Are we asking the right questions?). PACE 1988; 11; 1105-1107. Higard J, Ezri M, Denes P. Significance of ventricular pauses of three seconds or more detected on twenty-four-hour Holter recordings. Am J Gardiol 1985; 55:1005-1008. Gibson TC, Heitzman MR. Diagnostic efficacy of 24-hour electrocardiographic monitoring for syncope. Am J Cardiol 1984; 53:1013-1017. Murdock GI, Klein CJ, Yee R, et al. Feasibility of long-term electrocardiographic monitoring with an implanted device for syncope diagnosis. PACE 1990; 13:1374-1378.
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PACE, Vol. 15
SGARBOSSA, E.B., ET AL,: Incidence and Predictors of Syncope in Paced Patients with Sick Sinus Syndrome. In spite of a normal pacemaker/unction, syncope stilJ occurs in some patients with sick sinus syndrome fSSS). Causes often remain unknown. To identify predictors and etiologies of this bothersome symptom, we studied 507 patients who received atriaJ, ventricular, and duaJ-chamber pacemakers for SSS. During a mean foiJow-up of 62 ± 38 months, actuarial incidence of syncope was 3% at 1 year, 8% at 5 years, and 13% at 10 years. Causes were vasovagaJ (18%), orthostatic hypotension (25.5%), rapid atrial tachyarrhythmias fn.5%), venfricuJar tachycardia (5%), acute myacardial ischemia (2.5%), and pacemaker/Jead malfunction {6.5%}. In 13 patients (29.5%), syncope remained unexplained. The only preimplanf predictor for syncope was syncope as primary indication for pacemaker implant. Electrocardiographic correlation with bradycardia was not a predictor of relief of syncope during the follow-up. In conclusion: (1) syncope in paced patients with SSS has multiple etiologies and may be muJtifactorial; (2) the only predictor of syncope after pacemaker implant is the occurrence of preimplant syncope as the main indication for pacing; (3) extensive Holter monitoring is not usefuJ to document bradycardic origin of syncope nor to predict its recurrence; (4) SSS probably overlaps with other entities such as autonomic dysfunction, vasovagaJ syncope, carotid sinus hypersensitivity, and venous pooling, which wouJd provide an expJanation for recurrent syncope in patients with normaJ pacemaker function. (PACE, Vol. 15, November, Part II 3 992) pacing, sick sinus syndrome, syncope
Introduction Syncope is a common clinical problem, accounting for 3% of emergency room visits and 6% of medical admissions to general hospitals.^'^ It is particularly common in the elderly, with an annual incidence of 6% to 7%^'* and carries considerable morbidity from trauma. The diagnosis of sick sinus syndrome (SSS) can frequently be made in elderly patients with syncope, usually mandating permanent pacing. Chronic pacing is effective in suppressing recurrent syncope in most patients with SSS.^ However, syncope may recur after pacemaker implantation or, if absent before, may develop de novo. Although syncope in paced patients has been often attributed to pacemaker mal-
function or ventricular arrhythmias, a recent report on patients with ventricular pacemakers concluded that pacemaker dysfunction was not a major cause of syncopal episodes, and that these are most often of vasovagal origin.^ Most likely, etiologies are multiple. To our knowledge, no large study has analyzed the actuarial incidence and predictors of syncope in paced patients with SSS, nor assessed the possible role of different pacing modalities. In the present study, we summarize the data obtained through a long-term follow-up on a population with atrial, ventricular, and dual-chamber pacemakers. Methods Study Patients
Address for reprints: James D. Maloney, M.D., Dept. of Cardiology, Desk F 15, The Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, Fax: (216) 444-0456,
PACE, Vol. 15
Between January 1980 and December 1989, we implanted an initial pacemaker in 507 adult
November, Part II 1992
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SGARBOSSA, ET AL.
patients (age more than 18 years) with SSS. SSS was defined by the presence of inappropriate, persistent sinus bradycardia [rate < 50 beats/min), sinus pauses longer than 3 seconds, or sinoatriai block. Patients in permanent atrial fibrillation at time of implant or with complete atrioventricular (AV) block or type II second degree AV block were excluded from the study. Baseline demographic variables as well as cardiac and concomitant diseases, electrocardiographic findings and pacing modes were analyzed (Table I). All patients were symptomatic, required bradycardia-producing drugs for treatment of tachyarrhythmias, or both. Syncope was the most common preimplant symptom, accounting for 39% of all indications for pacing (Fig. 1). Documentation of symptomatic hradycardia, e.g., its simultaneous occurrence with syncope, was consid-
Table I. Patient Characteristics
Need for Drugs 10% Near Syncope 9%
Syncope 39%
Figure 1. Specific indications for pacing.
ered desirable but not imperative for pacemaker implantation. During the second half of the study period, tilt-table testing was performed where indicated as part of the work-up of patients with syncope/ Pacing modes selected are depicted in Figure 2. Follow-Up
Clinical variables Age, years Maie/Female No structural heart disease
66 ± 12 308/199 211 (42%)
Structural heart disease* Coronary artery disease Valvular heart disease Mitrai valve prolapse Cardiomyopathy
217 (43%) 61 (12%) 35 (7%) 35 (7%)
Concomitant diseases Hypertensicn Diabetes Cerebrovascular disease Peripheral vascular disease
217 (43%) 72 (14%) 101 (20%) 45 (9%)
Electrocardiographic findings Bundle branch block Prolonged sinus pauses (more than 5
Fatigue 4%
77 (15%) 52 (10%)
The outcome end point for the study was the occurrence of syncope after pacemaker implant. Near-syncope was not analyzed. Patients were followed-up for a mean of 62 ± 38 months. Followup began on the date of pacemaker implant, and ended on the date of the first episode of syncope, the patient's death, or the end of the study. Symptoms and survival status were ascertained through review of medical records, questionnaires completed hy the patient's private physician, and telephonic interviews with the patients or their families. Follow-up was complete in 98.5% of the patients.
Dual-chamber 376 74%
sec) Paroxysmal atrial arrhythmia Complex ventricular arrhythmia
375 (74%) 162 (32%)
Documentation of symptomatic bradycardia among patients with syncope
78 (15%) Ventricuiar 112 22%
' Some patients had more than one cardiac disease.
2056
Atrial 19 4%
November, Part II 1992
Figure 2. Pacing modes selected.
PACE, Vol. 15
SYNCOPE IN SICK SINUS SYNDROME
tion for pacing was the only predictor of postimplant syncope [P < 0.001; hazard ratio = 3.9; 95% confidence interval = 2.0 to 7.4). Neither the clinical variables analyzed nor the pacing modalities were predictors of syncope during the follow-up. Among patients with preimplant syncope, recurrence of this symptom did not differ significantly between those with and without documentation of hradycardia or pauses as cause of preimplant syncope (P = 0.3). Causes of syncope, results of eventual tilt-table tests, pacing mode, and presence of ECC correlation with syncope are listed in Tahle II.
0.500
O
0.000
60
100
80
120
MONTHS
Figure 3. Actuarial incidence of syncope.
Discussion Statistical Analysis Continuous variables are presented as mean ± 1 SD. Actuarial curves for the incidence of syncope for each analyzed variahle were calculated with the method of Kaplan and Meier and compared hy means of the log-rank test. A P vaiue < 0.05 was considered significant.
Results During follow-up, 44 out of 507 paced patients (8.6%) had recurrence or syncope de novo. Actuarial incidence of syncope was 3% at 1 year, 8% at 5 years and 13% at 10 years (Fig. 3). This proportion markedly increases to 20% for the suhgroup of patients whose indication for pacing was syncope (Fig. 4). Syncope as primary indica-
iCOPE
0.500 • - - No PfBvkxjs Syncopo 13/311 Pr«vtous Syncope 31/196 0.375
in IL
NCI DENCE
O
0.250
0.125
0.000
'^--'•---T
40
60
80
100
120
140
MONTHS
Figure 4. Actuarial incidence of syncope in patients with and without syncope as indication for pacemaker implantation.
PACE, Vol. 15
Syncope is not an uncommon event in paced patients with SSS. Our 10-year actuarial incidence of 9% is similar to that in a recent report.^ As in other populations, syncope can be secondary to a myriad of etiologies.^ Vasovagal and carotid sinus syncope, orthostatic hypotension, drugs, ventricular and supraventricular tachyarrhythmias all need to be considered. Additional potential causes in paced patients are pacemaker malfunction and the pacemaker syndrome.^" Through extensive work-up, the mechanism of syncope could he explained in 71% of our patients. In previous series, the etiology of syncope in paced patients remained unknown in as many as 66% of cases. ^ ^ Orthostatic hypotension was the most frequent cause of syncope in our population. Few patients had full evidence of autonomic insufficiency. In others, orthostatic hypotension was secondary to relative hypovolemia, venous blood pooling, and/or drugs. Similarly, in a prospective study of unpaced patients with syncope, orthostatic hypotension was common in patients in whom an alternative cause was initially assigned, representing 31% of the cases.^^ Vasovagal syncope was the second most frequent etiology in our patients, accounting for 18% of the cases. Orthostatic hypotension and vasovagal syncope can be diagnosed hy the tilt-table test. However, there are no "gold standards" for diagnosing the cause of syncope of unknown etiology.^^ Only two of our patients had baseline tilttahle testing. One with subsequent syncope due to orthostatic hypotension had a normal study, whereas another one with vasovagal syncope during follow-up had a positive test.
November, Part II 1992
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SGARBOSSA. ET AL.
Table II Patients with Syncope During the Follov^r-Up Patient No.
1 2 3 4 5 6 7 8 9
42 74 57
M M F
M M M M F M M F
M M F M M M F
M F M F M M F F
M M F F M F M M
F F F M Ll_
42 43 44
M M
LL
40 41
Age
LL
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39
Gender
F
68 74 85 67 71 53 70 77 56 64 66 61 47 51 71 25 59 78 53 81 41 68 75 39 50 67 56 46 71 82 58 66 80 73 87 76 76 64 75 62 66
Pacing Mode
Prior Syncope
DVI AAI DDD DDD DDD DDD DDD
Y N Y N Y
DDD DVI
N
VVI VVI DVI DDD DDD VVI VVI DVI DDD DDD DDD DDD DDD VVIR DVI VVI DDD DDD DDD DVI DDDR DVI
DDD VVI VVI VVI DDD VVI DDD VVI DDD DDD AAI DDD DDD
N Y
Y Y Y Y Y Y
Y Y Y Y Y
Y Y
Y N N Y Y Y Y Y Y Y
Y Y
N N N Y
Y N N N
Y Y Y
HUT
Diuretics
Antihypertensives
Etiology
Normal NP NP
7
?
N N Y N N Y Y N ? N N N
N
Atrial Fib Exit block Ortho Hypo Unexplained Ortho Hypo Ortho Hypo Unexplained Unexplained Unexplained Ortho Hypo Unexplained Vasovagal Ortho Hypo Unexplained Vent Taohy Ortho Hypo Atrial Fib Unexplained Ortho Hypo Battery Deple Ortho Hypo Vent Tachy Vasovagal Valsa Unexplained Vasovagal Valsa Ortho Hypo Vasovagal Vasovagal Vasovagal Unexplained Atrial Fib Vasovagal Ortho Hypo Unexplained Atrial Flutter Ortho Hypo Unexplained Unexplained Unexplained Ortho Hypo Vasovagal Valsa Battery Deple Acute Ml Atrial Fib
NP NP (+) NP NP NP
NP NP Normal NP Normal NP NP NP NP (+) NP NP
NP NP NP NP
NP NP (+) NP
NP NP (+) NP
Normal Normal Normal NP NP NP NP NP NP NP NP
Y Y ? ? Y N N ? N
Y N Y
Y N N N N N N N
Y
N Y Y N Y N N ? N N Y N N ? ? Y N
N ? Y N
N Y N N N N
N N
N N Y
N N N N ?
N N
Y
Y ? N ? N
? N ? Y
Y N 9
Deple = depletion; Fib = fibrillation; HUT = head-up tilt test; Ml = myocardial intarction; NP = not performed; Ortho Hypo = orthostatic hypotension; Vasovagal Valsa = vasovagal during Valsalva maneuver; Vent Tachy = ventricular tachycardia; ? = information not available.
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November, Part II 1992
PACE, Vol. 15
SYNCOPE IN SICK SINUS SYNDROME
It should be noted that pacing that is successful in treating bradycardia-induced symptoms may not be effective in preventing syncope originated in an abrupt fall in total peripheral resistance, a common final pathway for vasovagal and orthostatic mechanisms. Conventional DDD pacing may abolish syncope due to carotid sinus hypersensitivity,^^'^^ but does not appear to prevent vasovagal syncope.^^ Recently, special AV sequential pacing modalities, including DVI pacing with a short AV delay and rate hysteresis^''and DDD pacing with a 50/100 hysteresis,'" were shown to abort vasovagal reactions in the setting of tilt-tahle testing. They appear to work by preventing marked falls in the blood pressure that follow hradycardia. Rapid atrial fibrillation and flutter caused 12% of the syncopal episodes. The pathophysiology of syncope in patients with atrial tachycardias is not fully understood. A short cycle length during the tachyarrhythmia may not be sufficient per se to account for the loss of consciousness; some patients with very rapid ventricular responses never have syncope, but palpitations or shortness of breath. An inadequate hemodynamic response to the tachycardia, similar to that of the vasovagal syncope, may be the underlying mechanism for fainting in patients with atrial tachyarrhythmias.'^ As in other studies,^-^ pacemaker malfunction was not an important cause of syncope during the follow-up. Exit block was identified in one patient with an AAI pacemaker and the system was changed for a VVI unit. Another two patients were found to have early battery depletion and their generators replaced. Pacemaker syndrome was not incriminated as the cause of syncope in any patient. However, other symptoms compatible with pacemaker syndrome mandated upgrade to a dual-chamber pacemaker in 9% of the patients with ventricular pacemakers. Mixed or vasodepressor forms of carotid sinus hypersensitivity could have hoen involved in some patients in whom the etiology of syncope remained unknown. Carotid sinus hypersensitivity was not systematically evaluated in our population prior to pacemaker implant, hut it is present in 8% of patients with SSS.^° Pacing has been shown to be unable to abolish symptoms in most patients with isolated vasodepressor or mixed response to carotid hypersensitivity.'^'^'
PACE, Vol. 15
Current joint ACC/AHA guidelines for implantation of pacemakers require the documentation of symptomatic bradycardia or pauses to qualify as a class I indication for pacing in SSS.^^ However, the lack of strict correlation between symptoms and the ECG should not preclude pacemaker implantation when felt clinically indicated.^^•^•' During Holter monitoring, the likelihood of recording a fortuitous bradyarrhythmic symptomatic event is discouragingly low.^^-^^ Electrocardiographic documentation may be feasible only in highly preselected populations undergoing very prolonged monitoring.^'^ We found a relatively low proportion (15%) of documented bradycardia as the cause of preimplant syncope, in spite of the significant number of 24-hour ambulatory Holter monitors and in-hospital telemetries [mean: 3.1 sessions per patient) available for analysis in these patients. In a subgroup of patients with SSS and paroxysmal symptoms, Lamas et al.^^ reported a documented symptomatic bradycardia in nearly 50%; however, their definition of documentation was less stringent since it included correlation with near-syncope as well. Interestingly, neither in our study nor in Lamas' did the documentation of symptomatic bradycardia prior to implant improve the likelihood of symptom relief.
Conclusions In paced patients w^ith SSS, syncope is a relatively common event, particularly when the indication for pacing is syncope. Moreover, this indication is the only predictor for recurrence during the follow-up. The search for a strict symptomECG correlation does not seem to improve the likelihood of syncope relief. Causes of these episodes remain unclear in more than 20% of patients. Vasovagal syncope and orthostatic hypotension are the most frequent mechanisms. Current pacing modalities may not be sufficient to circumvent these disorders. Tachyarrhythmias and pacemaker malfunctions are less prevalent etiologies. There is probably overlap between SSS and other entities, such as autonomic dysfunction, vasovagal syncope, carotid sinus hypersensitivity, and venous pooling, which would explain that some patients with SSS remain symptomatic in spite of normal pacemaker function.
November, Part II 1992
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SGARBOSSA. ET AL.
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