Neurally Mediated Syncope Detected by Carotid Sinus Massage and Head-Up Tilt Test in Sick Sinus Syndrome Michele Brignole, MD, Carlo Menozzi, MD, Lorella Gianfranchi, MD, Daniele Oddone, MD, Gino Lolli, MD, and Antonio Bertulla, MD
It is generally accepted that a positive response to carotid sinus massage (CSM) or head-up tilt (HUT) in patients affected by syncope suggests a reflex cause of the syncope. To study the role of the autonomic nervous system in causing syncope in the sick sinus syndrome (SSS), CSM and HUT were performed in 35 consecutive patients (20 men, mean age 70 f 9 years) with syncope and SSS. Results were compared with those in 35 patients affected by syncope that, despite careful cardiovascular and neurologic examination, were of uncertain origin (21 men; mean age 66 f 9 years) and with those of 35 subjects without syncope (20 men; mean age 69 f 10). All patients underwent CSM in the supine and standing positions for 10 seconds and HUT to 60” for 60 minutes. In the patients with SSS, the full reproduction of spontaneous symptoms by CSM occurred in 21 (60%) and by HUT, in 19 (54%). At least 1 test was positive in 28 patients (80%): cardioinhibitory or mixed responses in 69%, vasodepressor responses in 11%. The percentages of positive tests in the patients with syncope of uncertain origin were similar to or slightly less than those of patients with SSS (CSM 63% HUT 26%, overall 74%) with cardioinhibitory or mixed responses in 54% and vasodepressor in 20% (p CO.05). In control subjects, syncope was induced by CSM in 1 (3%) and by HUT in 2 (6%); overall positivity was 9%. In conclusion, in most patients affected by syncope and SSS, an abnormal neural reflex probably plays a major role in causing syncope. Recause bradycardic patients have similar features to nonbradycardic patients, the autonomic disorder appears to be unrelated to sinus node dysfunction, although the intrinsic dysfunction of From the Laboratory of Electrophysiology and Pacing, Cardiology Department, Hospital of Lavagna (GE), and the Division of Cardiology, Hospital of Reggio Emilia, Italy. Manuscript received March 11, 1991; revised manuscript received June 7, 1991, and accepted June 9. Address for reprints: Michele Brignole, MD, Via A Grilli 164, 16041 Borzonasca (GE), Italy.
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 68
the sinoatrial node probably enhances the cardioinhibitory reflex. (Am J Cardiol 1991;68:1032-1036)
yncope can occur in patients affected by sick sinus syndrome (SSS). A disorder of the automatic properties of the sinus node or a sinoatrial block are frequently consideredthe cause, but a direct association of spontaneous syncope with a bradyarrhythmia of significance can rarely be observed,either during electrocardiographic monitoring or during electrophysiologic testing.l-4 The importance of the influence of the autonomic nervous system over sinus node function is well known.5>6Carotid sinus massage(CSM) and head-up tilt (HUT) are often used to elicit vasovagalreflexes. It is generally acceptedthat a positive responseto one of these tests suggestsa diagnosis of neurally mediated syncopein patients with no other detectable cause.7-13 CSM is frequently positive in patients with SSS.r4-16 HUT has not yet been widely studied in patients with SSS; in 1 study,12HUT was positive in 14%of patients with asymptomatic sinus bradycardia. This study tests the hypothesisthat autonomic nervous systemdisorders can be an alternative mechanism in causing syncopein patients with SSS.
A group of 35 patients with syncope and SSS was comparedwith a group of patients with syncope of uncertain origin with normal sinus rate and with a group of patients without syncope.All the patients underwent CSM and HUT. Sick sinus syndrome group: This group consistedof 35 consecutivehospitalized patients affected by syncope and by SSS. Their clinical features are summarized in Table I. SSS was diagnosedon the basis of: ( 1) persistent, diurnal heart rate 385 ms after autonomic blockade. Electrophysiologic study including autonomic blockade was performed in 31 patients; in 4 patients with severepersistent bradycardia we performed a simplified electrophysiologic study including sinus node recovery time in the control state. Mean heart rate at rest was 53 f 10 beats/min, mean intrinsic heart rate was 65 f 10 beats/min (abnormal in 15 patients), mean basal corrected sinus node recovery time was 976 f 1,156 ms (abnormal in 17 patients), and mean intrinsic corrected sinus node recovery time was 1,380 f 1,752 ms (abnormal in 2X patients); overall intrinsic sinus node dysfunction was present in 29 of 31 patients who received autonomic blockade. In 3 patients, overdrive suppression after autonomic blockade induced asystolic pausesof 7.2, 6 and 5.5 seconds,respectively, which causeddizziness. All patients underwent prolonged electrocardiographic monitoring of 2% hours’ duration; a bradyarrhythmia that caused presyncopewas recorded in 2 of the patients who had symptoms induced during sinus node recovery time (in 1 patient sinoatrial blocks and a sinus pause of 3.6 seconds,in the other a sinus slowing followed by a sinus arrest of 4.1 seconds).
“thcertain syncope” group: This group consistedof 35 hospitalized patients affected by syncopc of uncertain origin matched with the patients of the SSS group for age, sex and presenceof structural heart disease. They were randomly selectedby a computerized program (dBASE III PLUS software) from our data base of patients affected by syncopeof uncertain origin. This data baseconsistsof hospital in-patients affected by recurrent severesyncopesin whom a diagnosiscould only be presumedon the basis of a history of remote or recent syncopal episodes,suggestinga situational or neurally mediated syncope3T4 or in whom syncopal origin remained totally unexplained. All patients underwent a careful standardizedbasic investigation including: ( 1) a complete history and physical and neurologic examination performed by one of the investigators; (2) baseline laboratory testing; (3) 12-lead electrocardiography; (4) prolonged electrocardiographic monitoring of 224 hours’ duration either by ambulatory or telemetry monitoring in a coronary care unit; (5) chest x-ray; (6) Mmode and 2-dimensional echocardiographic evaluation of cardiac function; and (7) definite evaluation of any clinical or historical finding suggestiveof the cause of the syncope. Control group: The control group consisted of 35 subjects without history of syncopc, matched with the patients with SSS for age, sex and presenceof structural heart disease(Table I). Induction tests: All patients and control subjectsunderwent CSM and HUT, in that order. The tests were
REFLEX SYNCOPES IN SICK SINUS SYNDROME
TABLE II Positive Responses (absolute number and percentage) to Carotid Sinus Massage and Head-Up Tilt in Control Subjects, and in Groups with Sick Sinus Syndrome and Uncertain Syncope
Development of Syncope
Control Subjects (35 pts.)
Carotid sinus massage(%) Head-up tilt (%) Carotid sinus massageor head-up tilt !%)
1 (3)* 2 (6)* 3 (9)*
Sick Sinus Syndrome (35 pts.)
Uncertain (35 pts.)
19 (54) 28 (80)
9 (26)t 26 (74)
between control and sick sinus syndromegroups: p ~0.05. between sick sinus syndrome and uncertain groups; p < 0.05.
TABLE Ill Comparison Between Groups with Sick Sinus Syndrome and Uncertain Syncope
Positive carotid sinus massage Total positivity (%I Cardioinhibitoty or mixed type (%) Vasodepressortype (%) Max. RR interval (ms * 1 SD) Lower systolic BP (mm Hg i 1 SD) Positive head-up tilt Total positivity (%I Asystole 2 3 sec. (%) Cardioinhibitory or mixed type (%) Vasodepressortype (%I Lower HR (beatslmin IT 1 SD) Lower systolic BP (mm Hg f 1 SD) BP = blood pressure; HR = heart rate; Max. = maximal;
No. of Pts. with SSS
No. of Pts. with Syncope of Uncertain Origin
(n = 35)
(n = 35)
21 (60) 20 (57) 1 13) 7,083 f 1,920 80 f 23
22 (63) 16 (46) 6 (17) 5,728 -+ 2,376 77 f 19
19 4 10 9
(54) (11) (29) (26)
9 0 4 5
41 * 13 512 3 SD = standard
(26) (0) (11) 114) 42 f 6
0.01 0.06 0.07
51 f 3
SSS = sick sinus syndrome.
cardioinhibitory or vasodepressorreflex caused no, or mild, symptoms. Cardioinhibitory responseduring CSM was defined as the development of ventricular asystole lasting >3 seconds,and during HUT as the development of ventricular asystole lasting L3 secondsor heart rate 145 beats/min with a percent decrease 230% in baseline heart rate. Vasodepressorresponsewas defined as a decreasein systolic blood pressureto 580 mm Hg. Mixed responsewas defined as the associationof both. These limits were arbitrarily chosen based on published repOl-tS.8~9 Head-up tilt test10-13-1s: A manual tilt table with ports and on our own experiencethat symptomsusually footplate support and