Mechanism of syncope in patients with bundle branch block and negative electrophysiological test.

BACKGROUND: In patients with syncope and bundle branch block (BBB), syncope is suspected to be attributable to a paroxysmal atrioventricular (AV) block, but little is known of its mechanism when electrophysiological study is negative. METHODS AND RESULTS: We applied an implantable loop recorder in 52 patients with BBB and negative conventional workup. During a follow-up of 3 to 15 months, syncope recurred in 22 patients (42%), the event being documented in 19 patients after a median of 48 days. The most frequent finding, recorded in 17 patients, was one or more prolonged asystolic pause mainly attributable to AV block; the remaining 2 patients had normal sinus rhythm or sinus tachycardia. The onset of the bradycardic episodes was always sudden but was sometimes preceded by ventricular premature beats. The median duration of the arrhythmic event was 47 seconds. An additional 3 patients developed nonsyncopal persistent III-degree AV block, and 2 patients had presyncope attributable to AV block with asystole. No patients suffered injury attributable to syncopal relapse. CONCLUSIONS: In patients with BBB and negative electrophysiological study, most syncopal recurrences have a homogeneous mechanism that is characterized by prolonged asystolic pauses, mainly attributable to sudden-onset paroxysmal AV block.

Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families.

BACKGROUND: The ECG pattern of right bundle branch block and ST-segment elevation in leads V(1) to V(3) (Brugada syndrome) is associated with high risk of sudden death in patients with a normal heart. Current management and prognosis are based on a single study suggesting a high mortality risk within 3 years for symptomatic and asymptomatic patients alike. As a consequence, aggressive management (implantable cardioverter defibrillator) is recommended for both groups. METHODS AND RESULTS: Sixty patients (45 males aged 40+/-15 years) with the typical ECG pattern were clinically evaluated. Events at follow-up were analyzed for patients with at least one episode of aborted sudden death or syncope of unknown origin before recognition of the syndrome (30 symptomatic patients) and for patients without previous history of events (30 asymptomatic patients). Prevalence of mutations of the cardiac sodium channel was 15%, demonstrating genetic heterogeneity. During a mean follow-up of 33+/-38 months, ventricular fibrillation occurred in 5 (16%) of 30 symptomatic patients and in none of the 30 asymptomatic patients. Programmed electrical stimulation was of limited value in identifying patients at risk (positive predictive value 50%, negative predictive value 46%). Pharmacological challenge with sodium channel blockers was unable to unmask most silent gene carriers (positive predictive value 35%). CONCLUSIONS: At variance with current views, asymptomatic patients are at lower risk for sudden death. Programmed electrical stimulation identifies only a fraction of individuals at risk, and sodium channel blockade fails to unmask most silent gene carriers. This novel evidence mandates a reappraisal of therapeutic management.

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.

[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.

[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.

Role of autonomic reflexes in syncope associated with paroxysmal atrial fibrillation.

OBJECTIVES: The purpose of this study was to evaluate the role of autonomic reflexes in the genesis of syncope associated with the onset of paroxysmal atrial fibrillation. BACKGROUND: Syncope associated with paroxysmal atrial fibrillation has been interpreted as an ominous finding predictive of rapid ventricular rates. However, various mechanisms may be involved when heart rate is not particularly high. METHODS: Forty patients (age 60 +/- 14 years, 20 men, 20 women) with syncope and atrial fibrillation were compared with atrial fibrillation without syncope. Carotid sinus massage and head-up tilt testing (at 60 degrees for 60 min at baseline and during isoproterenol infusion) were performed during sinus rhythm. A positive response was defined as the induction of syncope. Atrial fibrillation was also induced on a tilt table at 60 degrees by means of short bursts of atrial pacing. RESULTS: Results of carotid sinus massage were positive in 15 (37%) of 40 patients but in no control subjects (p = 0.002). Head-up tilt test findings were positive in 25 (66%) of 38 patients and in 2 (12%) of 16 control subjects (p = 0.0004). The induction of atrial fibrillation in the upright position elicited syncope in 16 (42%) of 38 patients but in none of 16 control subjects (p = 0.001). At the beginning of atrial fibrillation, systolic blood pressure was lower in patients than in control subjects (88 +/- 32 vs. 127 +/- 32 mm Hg), whereas mean heart rate was similar (142 +/- 35 vs. 134 +/- 25 beats/min). The correlation between heart rate and systolic blood pressure was weak (r = 0.35), and in five patients syncope occurred at a heart rate < or = 130 beats/min. At the time of syncope, heart rate decreased (-12 +/- 21 beats/min) in patients with induced syncope, whereas it remained unchanged in patients without induced syncope (+1 +/- 17 beats/min, p = 0.04) or slightly increased in control subjects (+9 +/- 21 beats/min, p = 0.009). CONCLUSIONS: Patients with syncope associated with paroxysmal atrial fibrillation are predisposed to an abnormal neural response during both sinus rhythm and arrhythmia. In some patients the onset of atrial fibrillation triggers vasovagal syncope.

An abnormal neural reflex plays a role in causing syncope in sinus bradycardia.

OBJECTIVES: This study investigates the role of an abnormal neural reflex in causing syncope in patients with sinus bradycardia. BACKGROUND: Syncope is commonly considered an indication of severity in sinus bradycardia. However, the occurrence of syncope is unpredictable, and the prognosis appears to be similar in patients with and without syncope. METHODS: Head-up tilt testing (60 degrees for 60 min), carotid sinus massage in the supine and standing positions, 24-h Holter ambulatory electrocardiographic (ECG) recording and electrophysiologic study before and after pharmacologic autonomic blockade were performed in 25 patients with sinus bradycardia and syncope (group I, sinus rate < 50 beats/min, age 71 +/- 12 years) and 25 patients with sinus bradycardia and no neurologic symptoms (group II, sinus rate < 50 beats/min, age 67 +/- 16 years). RESULTS: Clinical characteristics and ambulatory ECG monitoring data were similar in the two study groups. A positive response (induction of syncope or presyncope with hypotension and/or bradycardia) was obtained by head-up tilt testing in 15 group I (60%) and in 3 group II (12%) patients (p < 0.001) and by carotid sinus massage in 11 group I (44%) and 6 group II (24%) patients (p = NS). Results of at least one test (head-up tilt testing or carotid sinus massage, or both) were positive in 19 group I (76%) and 9 group II (36%) patients (p < 0.01). Basal and intrinsic corrected sinus node recovery time did not differ significantly between the two groups. An abnormal intrinsic heart rate was present in 66% of group I and 26% of group II patients (p < 0.01). The different percentage of positive findings on head-up tilt testing and carotid sinus massage in the two groups was independent of the presence of intrinsic sinus node dysfunction. CONCLUSIONS: These results indicate that an abnormal neural reflex plays a role in causing syncope in patients with sinus bradycardia. This reflex seems to be unrelated to the severity of sinus node dysfunction, even if the latter could enhance the cardioinhibitory response.

Carotid sinus massage, eyeball compression, and head-up tilt test in patients with syncope of uncertain origin and in healthy control subjects.

To verify the role of abnormal neural mechanisms in unexplained syncopes, we evaluated the results of carotid sinus massage (CSM), eyeball compression (EBC), and head-up tilt test (HUT) in the basal state (B) and during isoproterenol infusion (ISO) in: (1) 100 consecutive patients affected by syncope which, despite careful cardiovascular and neurologic examination, was of uncertain origin (age 60 +/- 18 years; 54 men) and (2) 25 healthy subjects matched 4:1 with the patients of the previous group. All the patients underwent CSM and EBC in the supine and standing position for 10 seconds and HUT at 60 degrees for 60 minutes; if HUT-B was negative (68 cases), it was repeated during ISO (1 to 5 micrograms/min) infusion. In the patients with uncertain syncope, spontaneous symptoms were fully reproduced in 49%, 16%, 32%, and 16% of cases respectively by means of CSM, EBC, HUT, and HUT-ISO; overall positivity for at least one test was observed in 79% of cases. The results of CSM, EBC, or HUT-ISO were linked to age, sex, and underlying heart disease. In the healthy subjects, syncope was induced by CSM, EBC, HUT, and HUT-ISO in one case each; overall positivity was 16%. In conclusion, neural reflex induction tests reproduced spontaneous symptoms in most patients affected by uncertain syncope, while they evoked normal responses in most healthy subjects. Therefore on the basis of results of induction tests, the diagnosis of neurally mediated syncope can be ascribed to most patients affected by syncope of uncertain origin.

Spontaneous occurrence of the induced cardioinhibitory vasovagal reflex.

ECG recording of spontaneous, neurally-mediated syncope is rare. We have observed ten patients who sustained 70 syncopal episodes in whom: (1) ECG monitoring recorded syncope caused by ventricular asystole (AV block, three patients; sinus arrest; seven patients); (2) syncope and the spontaneously observed arrhythmias were reproducible by carotid sinus massage, upright tilt test, or eyeball pressure; and (3) no discernable cause of precipitating factors were detected. Two patients had a history of cardiac disease and four patients had only mild nonclinical ECG or echocardiographic abnormalities. Syncopal episodes recorded during Holter monitoring were of sudden onset in four patients and preceded by prodromal symptoms in six patients. The maximum RR pause was 9.4 +/- 3.7 seconds (range 4.5-15). Electrophysiological evaluation was normal in seven patients. Slight sinus node dysfunction or atrioventricular conduction abnormalities were noted in three others. The clinical characteristics of spontaneous and induced episodes strongly suggest that increased vagal tone played a role in causing the spontaneous events. Vagal stimulation tests are useful for the diagnosis of syncope of unknown origin.

[Comparison of permanent cardiac pacing and cardiac pacing on demand in mixed carotid sinus syndrome. Acute- and medium-term follow-up study]. / Confronto tra stimolazione DVI e VVI nella sindrome del seno carotideo mista. Uno studio in acuto e a medio termine.

The aim of the study was to evaluate the importance of atrial synchronism for pacing therapy of patients with mixed carotid sinus syndrome. On 23 patients (21 m, 2 f; mean age 69 +/- 8 years) affected by symptomatic mixed carotid sinus syndrome we performed: 1) the study of ventriculo-atrial conduction, 2) the evaluation of pacemaker effect and 3) the carotid sinus massage in standing position during VVI and DVI temporary pacing. All patients received a permanent DVI pacemaker and then underwent a two-month period single-blind, randomized, cross-over study on DVI vs VVI mode. During DVI period, no syncope occurred in any patients, minor symptoms persisted in 11 (48%) of them; during VVI period syncopes recurred in 3 patients, symptoms requiring the withdrawal of VVI pacing and premature DVI reprogramming in 8, minor symptoms were observed in 17 (74%). A comparison between 14 patients who preferred DVI period (Group A) and the remaining 9 patients who had no preference for DVI and VVI period (Group B) revealed that Group A patients had a greater pacemaker effect (-34 +/- 16 mmHg vs -16 +/- 14 mmHg; p less than 0.02) and a higher prevalence of ventriculo-atrial conduction (78% vs 44%; p = 0.1), while the entity of the systolic pressure fall caused by carotid sinus massage was similar in the two groups both during VVI mode (Group A -51 +/- 16 mmHg vs Group B -56 +/- 27 mmHg) and DVI mode (Group A -38 +/- 17 mmHg vs Group B -45 +/- 17 mmHg).(ABSTRACT TRUNCATED AT 250 WORDS)

[Changes in sinus function at rest and during physical exertion after permanent atrial electrostimulation in patients with sick sinus syndrome]. / Studio delle modificazioni della funzionalità sinusale a riposo e durante sforzo fisico dopo elettrostimolazione atriale permanente in pazienti affetti da malattia del nodo del seno.

We studied the unnatural history of sinus node function in severe sick sinus syndrome treated with AAI or DDD pacemakers. In 19 patients (10 m; 9 f; mean age +/- 1 SD 69 +/- 7 years) we executed serial bicycle exercise tests and electrophysiological studies before, 7 days and 3 months after pacemaker implant. Sinus heart rate at maximum effort was: 118 +/- 23 beats/min and 117 +/- 23 beats/min (two different evaluations) before pacemaker implant, 125 +/- 21 beats/min after 7 days (p less than 0.05) and 133 +/- 20 beats/min after 3 months (p less than 0.001) with an average increment of 12.7%. A positive correlation (y = 50.4 + 0.7 X beats/min; p less than 0.001) between the first basal test and the third month one was found. In analogy exercise test lasted 8.7 +/- 3, 8.6 +/- 2.8, 9.5 +/- 2.5, 9.7 +/- 2.5 minutes respectively, with an average increment of 11.5% between the first basal test and the third month one. Sinus heart rate at maximum effort in 14 age matched normal subjects was 138 +/- 15 beats/min. The difference with sick sinus syndrome patients was statistical (p less than 0.05) when compared with the basal test but not with 3rd month test. Parameters determined during electrophysiological studies were: spontaneous heart rate, corrected sinus node recovery time, sino-atrial conduction time evaluated before and after autonomic blockade (propranolol 0.2 mg/kg i.v. plus atropine 0.04 mg/kg i.v.). All these parameters, excepting basal corrected sinus node recovery time, improved significantly after pacemaker implant.(ABSTRACT TRUNCATED AT 250 WORDS)

[Association of the carotid sinus syndrome and orthostatic hypotension. Another potential cause of the failure of VVI electrostimulation]. / L'associazione di sindrome del seno carotideo ed ipotensione ortostatica. Un'altra possibile causa di insuccesso dell'elettrostimolazione VVI.

The systolic blood pressure was measured during clinostatism and 15'', 1', 5' after standing in 101 patients with carotid sinus syndrome and in 101 controls matched for age, sex, and prevalence of organic heart disease. In the carotid sinus syndrome group we observed a greater systolic blood pressure reduction from the supine to standing position (20 +/- 19 vs 14 +/- 11 mmHg), a lower orthostatic pressure (111 +/- 23 vs 120 +/- 21 mmHg) and a greater incidence of orthostatic hypotension (defined as a blood pressure reduction greater than or equal to 50 mmHg or greater than or equal to 20 mmHg when orthostatic pressure was lower than 100 mmHg) (35% vs 17%). Twenty-three carotid sinus syndrome patients received a VVI pacemaker for control of their symptoms; after a mean follow-up of 12.2 +/- 7.7 months, unchanged or reduced symptoms persisted in 6 out 9 (67%) patients with previous orthostatic hypotension while only in 1 out of 14 (7%) patients without this feature. In conclusion, orthostatic hypotension is frequently associated with a carotid sinus syndrome and may account for relapses in some patients treated with VVI pacing.