Clinical features of adenosine sensitive syncope and tilt induced vasovagal syncope.

AIM: To evaluate the possible relation between adenosine sensitive syncope and tilt induced vasovagal syncope. METHODS: An ATP test and a head up tilt test were performed in 175 consecutive patients with syncope of uncertain origin. The ATP test consisted of the rapid intravenous injection of 20 mg of ATP; a positive response was defined as the induction of a ventricular pause (maximum RR interval) >/= 6000 ms. The head up tilt test was performed at 60 degrees for 45 minutes; if negative, 0.4 mg oral glyceryl trinitrate spray was given and the test continued for a further 20 minutes; a positive response was defined as induction of syncope in the presence of bradycardia, hypotension, or both. RESULTS: Of the 121 patients with a positive response, 77 (64%) had a positive head up tilt alone, 18 (15%) had a positive ATP test alone, and in 26 (21%) both ATP and head up tilt were positive. Compared with the patients with isolated positive head up tilt, those with isolated positive ATP were older (mean (SD) age, 68 (10) v 45 (20) years), had a lower median number of syncopal episodes (2 v 3), a shorter median duration of syncopal episodes (4 v 36 months), a lower prevalence of situational, vasovagal, or triggering factors (11% v 64%), a lower prevalence of warning symptoms (44% v 71%), and a higher prevalence of systemic hypertension (22% v 5%) and ECG abnormalities (28% v 9%). The patients with a positive response to both tests had intermediate features. Of the 44 positive responses to the ATP test, atrioventricular block was the cause of the ventricular pause in 43; of the 29 positive cardioinhibitory responses to head up tilt, sinus arrest was present in 23 cases and atrioventricular block in six. CONCLUSIONS: ATP and head up tilt tests identify different populations of patients affected by syncope; these have different general clinical features, different histories of syncopal episodes, and different mechanism sites of action. Therefore, adenosine sensitive syncope and tilt induced vasovagal syncope are two distinct clinical entities.

New classification of haemodynamics of vasovagal syncope: beyond the VASIS classification. Analysis of the pre-syncopal phase of the tilt test without and with nitroglycerin challenge. Vasovagal Syncope International Study.

We believe that the pattern of blood pressure response to tilt during the time preceding the development of the vasovagal reaction may provide adjunctive diagnostic information. A group of 101 consecutive patients affected by syncope of uncertain origin underwent passive tilt testing for 45 min at 60 degrees followed, if negative, by oral (sublingual) trinitroglycerin (TNG) 0.4 microg with continuation of the test for 20 min. Three main patterns were observed: the classic (vasovagal) syncope pattern was observed in 36 patients who, during the preparatory phase, had a rapid and full compensatory reflex adaptation to upright position, resulting in stabilization of their blood pressure values until abrupt onset of the vasovagal reaction; the dysautonomic (vasovagal) syncope pattern was observed in 47 patients in whom steady-state adaptation to upright position was not possible. There was thus a progressive fall in their blood pressure until the occurrence of a typical vasovagal reaction; the orthostatic intolerance pattern was observed in 18 patients in whom there was a progressive fall in blood pressure, similar to that of the dysautonomic group, but this was not followed by a clear vasovagal reaction. Compared with the classic, the dysautonomic patients were older, had a higher prevalence of co-morbidities, a very much shorter history of syncopal episodes, and a prevalence of mixed and vasodepressor forms of the VASIS classification. The patients with orthostatic intolerance had clinical characteristics similar to the dysautonmic group but they could not be classified according to the VASIS classification. In conclusion, in patients with syncope, a variety of abnormal responses is observed during tilt testing, suggesting that different syndromes can be diagnosed by the test. A more detailed, although still arbitrary, classification may form the basis of a number of future drug and pacemaker trials, as well as help towards a greater understanding of the different mechanisms of tilt-induced syncope.

Head-up tilt testing potentiated with oral nitroglycerin: a randomized trial of the contribution of a drug-free phase and a nitroglycerin phase in the diagnosis of neurally mediated syncope.

BACKGROUND: Since the pharmacological challenge with nitroglycerin (NTG) follows the initial drug-free phase in current tilt testing protocols, the effects of nitroglycerin alone and the appropriate duration of the basal phase are unknown. METHODS: To optimize the test, a randomized intra-patient comparison of two protocols was undertaken: a conventional nitroglycerin test (cHUT) consisting of passive upright posture at 60 degrees for 45 min followed, if negative, by sublingual NTG 0.4 mg spray, with the test continued for 20 min; and, accelerated nitroglycerin test (aHUT) consisting of passive upright posture at 60 degrees for 5 min--to rule out orthostatic hypotension--followed by sublingual NTG 0.4 mg spray, with the test continued for 20 min. Eighty-four consecutive patients (33 males; mean age 55+/-22) with unexplained syncope underwent both cHUT and aHUT in a randomized sequence with a 24-72 h interval between them. Additionally, 25 age-matched control subjects underwent aHUT. RESULTS: In the drug-free phase, cHUT was positive in 15/84 patients (18%) and aHUT in 1/84 patients (1%). After NTG, cHUT and aHUT showed the same positivity rate of 33% (28/84 patients). The overall positivity rate was therefore higher with cHUT than with aHUT (51% vs 35%, P=0.04). Times to syncope were 29+/-12 min, (range 2-44) for cHUT drug-free phase, 5+/-2 min (range 2-9) for cHUT NTG phase, and 5+/-2 min (range 2-9) for aHUT. Only one (4%) of the control subjects had a positive response to aHUT. CONCLUSIONS: The contribution of NTG to the diagnosis is independent of the presence of an unmedicated phase. The appropriate duration of the NTG phase is 10 min. aHUT has good specificity, but a positivity rate lower than cHUT; thus a drug-free phase is necessary to increase the sensitivity of the test.

The natural course of untreated sick sinus syndrome and identification of the variables predictive of unfavorable outcome.

We performed a prospective study in 35 untreated patients aged > or = 45 years, who had a mean sinus rate at rest of < or = 50 beats/min and/or intermittent sinoatrial block, and symptoms attributable to sinus node dysfunction. The patients were followed up for up to 4 years (mean 17 +/- 15 months). During follow-up, 20 patients (57%) had cardiovascular events that required treatment: 8 had syncope (23%); 6 had overt heart failure (17%); 4 patients had chronic atrial fibrillation (11%); and 2 patients had poorly tolerated episodes of paroxysmal tachyarrhythmias (6%). Actuarial rates of occurrence of all events were 35%, 49%, and 63%, respectively, after 1, 2, and 4 years. At univariate analysis, age > or = 65 years, end-systolic left ventricular diameter > or = 30 mm, end-diastolic left ventricular diameter > or = 52 mm, and ejection fraction < 55% were predictors of cardiovascular events. At multivariate analysis, age, end-diastolic diameter, and ejection fraction remained independent predictors of events. Actuarial rates of occurrence of syncope were 16%, 31%, and 31%, respectively, after 1, 2, and 4 years. Both univariate and multivariate predictors of syncope were history of syncope and corrected sinus node recovery > or = 800 ms. A favorable outcome was observed in the remaining 43% of patients. Thus, clinical cardiovascular events occur in most untreated sick sinus syndrome patients during long-term follow-up, even though a favorable course can be expected in 43% of patients. The outcome can be partly predicted on initial evaluation. In the patients with a favorable outcome, treatment can safely be delayed.

Effects of long-term vasodilator therapy in patients with carotid sinus hypersensitivity.

BACKGROUND: In patients affected by carotid sinus hypersensitivity, long-term vasodilator therapy might increase the risk of syncopal episodes by reducing systolic blood pressure and venous return to the heart. METHODS AND RESULTS: Thirty-two patients (mean age 73 +/- 9 years; 20 men) who met all the following criteria were included: (1) one or more episodes of syncope occurring during long-term (>6 months) treatment with angiotensin-converting enzyme inhibitors, long-acting nitrates, calcium antagonists, or a combination of these; (2) a positive response to carotid sinus massage, defined as the reproduction of spontaneous syncope in the presence of ventricular asystole > or =3 seconds or a fall in systolic blood pressure > or =50 mm Hg; (3) negative workup for other causes of syncope. The patients were randomly assigned to continue or to discontinue use of vasodilators; carotid sinus massage was repeated 2 weeks after randomization. By the end of the study period, the baseline values of systolic blood pressure were significantly different between the 2 groups of patients both in supine (P=.01) and upright (P=.03) positions. Syncope had been induced by carotid sinus massage in 81% of patients in the "on-vasodilator" group and in 62% of patients in the "off-vasodilator" group (P=.21). The cardioinhibitory reflex was of similar magnitude in the 2 groups, being found in 50% of the patients in each group, with a maximum ventricular pause of 7.1 +/- 2.7 and 6.7 +/- 1.8 seconds, respectively. The percentage decrease of blood pressure did not differ between the 2 groups, even if, in absolute values, the baseline difference of blood pressure roughly persisted for the duration of the test. In consequence of that, the rise of blood pressure to similar values was delayed approximately 30 seconds in the "on-vasodilator" group and took more than 2 minutes to return to baseline values. CONCLUSIONS: In patients affected by carotid sinus hypersensitivity, chronic vasodilator therapy does not have a direct effect on carotid sinus reflexivity, although the delayed recovery of pretest blood pressure values could indirectly potentiate the severity of the clinical manifestations of the syndrome. The persistence of hypotension for a longer time after the end of the massage suggests that vasodilators cause an impairment of compensatory mechanisms.

Adenosine-induced atrioventricular block in patients with unexplained syncope: the diagnostic value of ATP testing.

BACKGROUND: ATP and its related nucleoside, adenosine, are ubiquitous biological compounds with potent depressant activity on the atrioventricular node. We hypothesized that an increased susceptibility of the atrioventricular node to adenosine may, in some cases, play a role in the genesis of syncope. METHODS AND RESULTS: The study was performed in two parts. In part 1, we evaluated the effects of a bolus injection of 20 mg ATP in a group of 60 patients (57+/-19 years, 31 men) with syncope of unexplained origin and in 90 control subjects without syncope (55+/-17 years, 46 men). In control subjects, the upper 95th percentile of the maximum RR interval distribution, during ATP-induced atrioventricular block (AVB), was 6000 ms. In the syncope group, 28% of patients had a maximum RR interval above this limit (P=.000). The distribution of the maximum RR interval below the 95th percentile was similar in the two groups. In part 2, we validated the ATP test in 24 patients who had the fortuitous ECG recording of a spontaneous syncope caused by a transient asystolic pause (AVB in 15 and sinus arrest in 9). The ATP test caused AVB with an asystolic pause of > or = 6000 ms in 53% of the patients with documented AVB but in none (0%) of the patients with documented sinus arrest (P=.01). Among the patients with spontaneous AVB, the ATP test was abnormal in 6 of the 7 patients (86%) in whom all conventional investigations for syncope had been negative and in 2 of the 8 patients (25%) who had shown positivity (P=.03). CONCLUSIONS: An increased susceptibility to ATP testing is present in patients with SUO and patients with syncope due to paroxysmal AVB. Thus, a logical inference is that ATP testing can be used to identify patients with syncope due to paroxysmal AVB. The results of this study form the necessary background for future prospective studies with an aim to validate this assumption.

Effects of chronic vasodilator therapy to enhance susceptibility to vasovagal syncope during upright tilt testing.

To evaluate the effect of chronic vasodilator therapy on susceptibility to vasovagal syncope, 45 patients with syncope and a positive response to tilt testing were randomly assigned to continue or to discontinue vasodilators. The study result demonstrated that chronic vasodilator therapy enhances susceptibility to vasovagal reaction during upright tilt testing.

Effects of permanent pacemaker and oral theophylline in sick sinus syndrome the THEOPACE study: a randomized controlled trial.

BACKGROUND: Pacemakers and theophylline are currently being used to relieve symptoms in patients with sick sinus syndrome (SSS). However, the impact of either therapy on the natural course of the disease is unknown. We conducted a randomized controlled trial to prospectively assess the effects of pacemakers and theophylline in patients with SSS. METHODS AND RESULTS: One hundred seven patients with symptomatic SSS (age, 73 +/- 11 years) were randomized to no treatment (control group, n = 35), oral theophylline (n = 36), or dual-chamber rate-responsive pacemaker therapy (n = 36). They were followed for up to 48 months (mean, 19 +/- 14 months). During follow-up, the occurrence of syncope was lower in the pacemaker group than in the control group (P = .02) and tended to be lower than in the theophylline group (P = .07). Heart failure occurred less often in patients assigned to pacemaker therapy and theophylline than in control patients (both, P = .05), whereas the incidence of sustained paroxysmal tachyarrhythmias, permanent atrial fibrillation, and thromboembolic events did not show any apparent difference among the three groups. Heart rate was higher in the theophylline group than in the control group. Both pacemaker therapy and theophylline improved symptom scores after 3 months of treatment; however, a similar improvement was observed in the control group. CONCLUSIONS: In patients with symptomatic SSS, therapy with theophylline or dual-chamber pacemaker is associated with a lower incidence of heart failure; pacemaker therapy is also associated with a lower incidence of syncope. The therapeutic benefits of pacemakers and theophylline on symptoms are partly a result of spontaneous improvement of the disease.

Mechanisms of syncope caused by transient bradycardia and the diagnostic value of electrophysiologic testing and cardiovascular reflexivity maneuvers.

Transient bradycardia may be intrinsic because of sinus node or atrioventricular (AV) conduction abnormalities, or extrinsic because of abnormal vagal reflex. Twenty-five consecutive patients, referred to us for study of unexplained syncope, who, during electrocardiographic monitoring, had a documented episode of intermittent bradycardia that caused syncope, underwent a full electrophysiologic study, carotid sinus massage, and the head-up tilt test. A prolonged ventricular asystole (5 to 20 seconds) was documented during syncope in all patients: sinus arrest in 13, AV block in 7, sinus arrest plus AV block in 3, and asystolic pause during atrial fibrillation in 2. Abnormal electrophysiologic findings suggested the correct diagnosis in 6 patients (24%): block within the bundle of His in 5 and sick sinus syndrome in 1. An abnormal response to carotid sinus massage or to the head-up tilt test suggested a neurally mediated mechanism in 17 patients (68%). Overall, electrophysiologic study and vasovagal maneuvers were able to identify the mechanism of spontaneous syncope in 23 patients (92%). Thus, in patients affected by syncope due to transient bradycardia, the most likely mechanism of syncope is neurogenic, whereas it is cardiogenic only in a few instances. Electrophysiologic testing, carotid sinus massage, and the head-up tilt test can identify most of these patients. Conversely, when all these tests are negative, it is unlikely that transient bradycardia is the cause of syncope. Because of the different mechanisms involved, electrophysiologic study and vasovagal maneuvers are complementary diagnostic tools.

[The re-evaluation of the vasodepressive component in the carotid sinus syndrome]. / Rivalutazione della componente vasodepressiva nella sindrome del seno carotideo.

BACKGROUND: The evaluation of the vasodepressor (VD) reflex of the carotid sinus syndrome is usually inaccurate, due to the difficulty in blood pressure measurement. AIM: To study the VD reflex with a beat-to-beat not invasive technique. METHODS: We investigated 68 patients (49 males, 19 females; mean age 70 +/- 11 years) affected by carotid sinus syndrome: cardioinhibitory (CI) form was present in 47 patients, mixed (M) form in 10 patients and VD form in 11 patients. The control group consisted of 9 patients (6 male, mean age 71 +/- 8 years) affected by third degree atrioventricular block who had received the implant of a permanent pacemaker and were pacemaker-dependent with a prolonged asystole at time of temporary inhibition of the pacemaker itself. The study of the VD reflex was performed in the supine position; beat-to-beat arterial systolic pressure was monitored by a photoplethysmographic method using a finger cuff (Finapres technique). RESULTS: In all the patients the carotid sinus massage caused a marked fall in systolic blood pressure which was greatest at the end of the massage: from 143 +/- 25 mm Hg to 74 +/- 20 mm Hg in the patients with CI form, from 144 +/- 14 mm Hg to 76 +/- 18 mm Hg in those with M form and from 125 +/- 26 mm Hg to 65 +/- 13 mm Hg in those with VD form. A decrease in systolic blood pressure > or = 50 mm Hg occurred in 84% of cases. Afterwards, the patients with CI form had a progressive increase of systolic blood pressure that reached the initial value after a mean of 27 seconds. In the patients with VD form systolic blood pressure was significantly (p < or = 0.5) lower than that observed in all the other groups, beginning from the third second after the end of the massage; mean systolic blood pressure value remained significantly lower than the initial value for more than 27 seconds. The patients with M form showed an intermediate pattern. Also control group patients showed a fall in systolic blood pressure immediately after pacemaker inhibition (from 152 +/- 29 mm Hg to 87 +/- 25 mm Hg) that was of similar extent than that observed in carotid sinus syndrome patients, but pressure returned to initial value within 9 seconds. CONCLUSIONS: An important VD reflex is present in most patients with carotid sinus syndrome. It lasts more than the CI reflex and it persists for several seconds after the end of the massage. The initial fall of systolic blood pressure is of similar extent in all the forms of carotid sinus syndrome, but the patients with the VD form are characterized by a longer duration and greater entity of the decrease. These results point out the importance of the VD reflex in patients with the carotid sinus syndrome.

A new pacemaker for paroxysmal atrial fibrillation treated with radiofrequency ablation of the AV junction.

Atrial fibrillation is a relative contraindication to atrial synchronous pacing because of the risk of the tracking of rapid atrial rhythms by the pacemaker. In this study, we describe the clinical results of an AV synchronous rate responsive pacemaker with an original algorithm, which is able to sense pathological increments in atrial rate and automatically to switch into a non-AV synchronous mode of pacing. This pacemaker was implanted in 12 patients who had undergone radiofrequency ablation of the AV junction in order to cure severely symptomatic, drug refractory, paroxysmal atrial fibrillation. In an acute, intrapatient comparison between the standard AV synchronous mode and the automatic switching mode, ventricular tracking of atrial fibrillation occurred in 35% and 4% of total beats at rest and in 24% and 2% of total beats during exercise, respectively (P < 0.001). During 5 +/- 4 months of follow-up, no further tachyarrhythmia related symptoms occurred. In conclusion, the standard DDDR mode is unable to eliminate ventricular tracking of atrial fibrillation, thus undermining the efficacy of AV junction ablation therapy. The automatic switching mode eliminates this adverse effect of dual chamber pacing.

Radiofrequency catheter ablation and modulation of atrioventricular conduction in patients with atrial fibrillation.

We attempted radiofrequency ablation of the AV junction with a sequential right- and left-sided approach in 78 patients affected by severely symptomatic, drug refractory atrial fibrillation. Stable third-degree AV block was obtained in 99% of cases and, after 3 months, persisted in 92% of cases. Single session, stepwise, radiofrequency modulation of the AV node was attempted in 13 patients with paroxysmal atrial fibrillation. During sinus rhythm, ablation of the slow and fast AV node pathways was performed in order to increase the nodal refractory period or to slow conduction. Clinically successful modulation of AV conduction was achieved in 15% of cases and persisted during a 3-month follow-up. In conclusion, AV junction ablation is a well-established means of treating atrial fibrillation, but implies the implant of a permanent pacemaker. AV node modulation avoids the pacemaker implant, but is efficacious only in a minority of patients. Thus, in patients affected by paroxysmal atrial fibrillation, AV modulation should be attempted first; if this is ineffective, AV ablation can be performed during the same session.

The effect of exogenous adenosine in patients with neurally-mediated syncope and sick sinus syndrome.

The effects of a 20-mg i.v., bolus of adenosine 5' triphosphate (ATP) on the heart rhythm was studied in 79 patients affected by neurally-mediated syncope (26 cases) or sick sinus syndrome (22 cases) or both syndromes (31 cases) and in 31 healthy control subjects in order to examine the sensitivity of cardiac purinoceptors in such circumstances. During ATP infusion, the sinus cycle lengthened to > 2 seconds in no control, in 1 (4%) patient with neurally-mediated syncope, in 5 (23%) patients with sick sinus syndrome, and in 13 (42%) patients with both neurally-mediated and sick sinus syndromes (P = 0.01). Atrioventricular block occurred in 14 (45%) of controls, in 10 (38%) patients with neurally-mediated syncope, in 4 (18%) patients with sick sinus syndrome, and in 13 (42%) patients with both neurally-mediated syncope and sick sinus syndrome (n.s.). Thus, exogenous ATP exerts different effects on patients with neurally-mediated syncope and patients with sick sinus syndrome. In fact, intrisic disease of the sinus node is necessary to modulate an abnormal adenosine-mediated sinus arrest, whereas patients affected by neurally-mediated syncope alone show a normal sensitivity to the drug administration. The effect of ATP on atrioventricular conduction is greater than that on sinus node and is of similar magnitude in patients and controls; thus the clinical meaning of ATP induced atrioventricular block remains uncertain.

Influence of atrioventricular junction radiofrequency ablation in patients with chronic atrial fibrillation and flutter on quality of life and cardiac performance.

The purpose of this study was to evaluate the effects of atrioventricular junction radiofrequency ablation on the quality of life, exercise performance, and echocardiographic parameters in 23 patients with chronic, severely symptomatic, drug-refractory atrial fibrillation or flutter. Initially, patients were randomized to receive ablation plus pacemaker therapy (n = 12) or pacemaker therapy alone (n = 11). After 15 days, palpitations decreased by 92% and 37% (p = 0.004), rest dyspnea by 79% and 40% (p = NS), effort dyspnea by 65% and 30% (p = 0.03), exercise intolerance by 54% and 17% (p = 0.005), and asthenia by 67% and 31% (p = 0.02) in the 2 groups, respectively. At the end of this short-term study, control patients also underwent ablation therapy, and a 3-month intrapatient follow-up study was performed in 22 patients. New York Heart Association functional class > or = 3 was present in 14 patients (64%) before, but in only 3 patients (14%) after ablation therapy (p = 0.002); specific activity scale functional class > or = 3 was present in 9 patients (41%) before, but in only 5 (23%) after ablation therapy (p = NS). Exercise duration during standardized stress testing increased by a mean of 63 +/- 93 seconds (15% increase) (p = 0.001). In the 9 patients with depressed left ventricular systolic function, echocardiographic fractional shortening increased by 34% (from 23 +/- 5% to 31 +/- 9%) (p = 0.003). In the remaining 13 patients with normal systolic function, fractional shortening decreased by 10% (from 40 +/- 5% to 36 +/- 6%) (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Progression to 2d and 3d grade atrioventricular block in patients after electrostimulation for bundle-branch block and syncope: a long-term study]. / La progressione a blocco atrioventricolare di II e III grado nei pazienti elettrostimolati per blocco di branca e sincope: uno studio a lungo termine.

BACKGROUND: Patients with bundle branch block and syncope, especially those with abnormal electrophysiologic study, are at high risk of progression to second-or third-degree atrioventricular block and therefore they often receive a permanent back-up pacemaker. The aim of this study was to evaluate of the incidence of bundle branch block progression to second or third-degree atrioventricular block during long-term follow-up. METHODS: A retrospective study was performed on 60 patients (49 males, age 77 +/- 9 years) with bundle branch block and permanent back-up pacemaker. The patients were subdivided into 3 groups: 13 patients, at pre-implant electrophysiologic study had HV interval > or = 100 msec and/or second- or third-degree atrioventricular block induced by ajmaline i.v. administration (Group 1); 20 patients with HV interval of 70-100 msec and/or HV > or = 120 msec after ajmaline administration (Group 2); 27 patients who had received a permanent pacemaker because of carotid sinus syndrome or sick sinus syndrome (22 patients) or because of recurrent syncopes and negative electrophysiologic study (5 patients) (Group 3). RESULTS: During a mean follow-up of 62 +/- 41 months, 17/60 patients (28%) had progression to second- (n = 4) or third-degree (n = 13) atrioventricular block: atrioventricular block occurred in 54% of Group 1 patients in 25% of Group 2 patients and in 19% of Group 3 patients. The actuarial rate of progression to atrioventricular block for the overall population was, at 5 and 10 years, 25% and 58% respectively; in Group 1 it was 46% and 62%; in Group 2 it was 22% and 55% and in Group 3 it was 21% and 59% (p = 0.06). The patients with right bundle branch block and left anterior hemiblock were at higher risk of progression to atrioventricular block than those with right bundle branch block or left bundle branch block (risk 42% vs 14%, p = 0.06). The presence of an abnormal electrophysiologic study did not increase the progression rate either in the patients with right bundle branch block and left anterior hemiblock (risk of 43%), nor did it in those patients with other types of bundle branch block (risk of 18%). Moreover, the induction of second- or third-degree atrioventricular block during ajmaline administration was associated with a higher risk of block during the follow-up (60% vs 25%, p = 0.06). CONCLUSIONS: Patients treated with pacemaker because of symptomatic bundle branch block have a high risk of progression to second- or third-degree atrioventricular block in the long-term follow-up. The results argue against the practical usefulness of electrophysiological study since a risk stratification could be obtained by the simpler surface electrocardiogram; moreover, risk of block was also present in the patients affected by carotid sinus syndrome or sick sinus syndrome, and in those affected by unexplained syncope with negative electrophysiologic study.

Follow-up of asystolic episodes in patients with cardioinhibitory, neurally mediated syncope and VVI pacemaker.

The occurrence rate of spontaneous asystolic episodes during long-term follow-up in patients with abnormal asystolic responses induced by means of vasovagal maneuvers was evaluated. The heart rate of 23 patients (mean age 64 +/- 12 years; 6 women and 17 men) affected by neurally mediated syncope (mean 4.3 +/- 4.9 episodes) was continuously monitored by a specially designed implanted pacemaker able to detect and store in its memory all asystolic episodes lasting 3 to 6 or > 6 seconds. Asystolic, neurally mediated syncope was diagnosed when a reflex asystole of > 3 seconds was induced during carotid sinus massage (n = 22), eyeball compression test (n = 3) or head-up tilt test (n = 2). During a total of 357 months (mean 15 +/- 7) of monitoring, asystolic episodes occurred in 17 patients (74%): 1,765 episodes of 3- to 6-second (median 3) duration occurred in 14 patients, and 47 episodes of > 6-second (median 2) duration occurred in 11. The actuarial estimates of occurrence of asystolic episodes of > 3 and > 6 seconds were 82 and 53%, respectively, after 2 years of follow-up. Only 12 episodes of 3 to 6 seconds (0.7%), and 20 episodes of > 6 seconds (43%) resulted in presyncopal or syncopal symptoms. Thus, an asystolic response to vasovagal maneuvers predicts the occurrence of spontaneous asystolic episodes during follow-up. With few exceptions, spontaneous episodes are asymptomatic and their incidence is low.

Long-term outcome of paced and nonpaced patients with severe carotid sinus syndrome.

The natural history of patients with severe carotid sinus syndrome, and the efficacy of permanent pacemaker treatment are not clearly known. A randomized treatment/nontreatment prospective study was performed in 60 patients affected by carotid sinus syndrome whose symptoms were judged to involve risk of major trauma or interfered with their daily activity. They were randomly assigned to 2 groups: 28 patients to no therapy (nonpacing group), and 32 to VVI (n = 18) or DDD (n = 14) pacemaker implant (pacing group). Syncope recurred in 16 patients (57%) of the nopacing group (mean follow-up 36 +/- 10 months) and in only 3 (9%) of the pacing group (mean follow-up 34 +/- 10 months) (p = 0.0002); moreover, 19 (68%) in the nonpacing group needed a secondary pacemaker implant because of the severity of symptoms. The actuarial rate of absence of syncopal recurrence after 1, 2, 3 and 4 years was 64, 54, 38 and 38%, respectively, for the nonpacing group, and 100, 97, 93 and 84%, respectively, for the pacing group (p = 0.0001). The actuarial rate of absence of minor symptoms after 1, 2, 3 and 4 years was 21, 14, 7 and 7%, respectively, for the nonpacing group and 66, 43, 27 and 27%, respectively, for the pacing group (p = 0.002). Reproducibility of carotid sinus reflex was tested after 15 +/- 8 months in 54 patients; an abnormal response to carotid sinus massage persisted in all 54. In conclusion, symptoms recur in most patients with untreated carotid sinus syndrome, and pacing is a useful therapy for preventing recurrences.