Usefulness of disopyramide for prevention of upright tilt-induced hypotension-bradycardia

Susceptibility to transient hypotension-bradycardia of neurally mediated origin has been attributed in part to accentuated afferent neural traffic arising from cardiopulmonary mechanoreceptors, and consequently, may be diminished by agents with anticholinergic and negative inotropic effects, such as disopyramide phosphate. This study assessed electrocardiographic and hemodynamic responses to upright tilt testing (alone or during isoproterenol infusion) before and after disopyramide therapy in 10 patients (age range 16 to 74 years) with recurrent syncopal episodes of neurally mediated origin. Untreated, syncope occurred at less than or equal to 7 minutes of tilt alone (6 patients) or tilt plus isoproterenol at less than or equal to 3 micrograms/min (4 patients) and was associated with hypotension (mean arterial pressure, 40 +/- 16 mm Hg vs baseline 76 +/- 10 mm Hg, p less than 0.001) and inappropriate heart rate slowing (mean heart rate, 59 +/- 39 beats/min vs baseline 88 +/- 18 beats/min, p less than 0.005). After oral disopyramide 150 mg 3 times daily (mean plasma level, 3.0 +/- 0.64 micrograms/ml), all patients tolerated 10 minutes of both tilt and tilt plus isoproterenol (maximum dose, 3 micrograms/min) without symptoms, hypotension (mean arterial pressure; tilt 1 min, 79 +/- 7 mm Hg vs tilt 10 min, 77 +/- 8 mm Hg, difference not significant) or bradycardia (mean heart rate; tilt 1 min, 81 +/- 12 beats/min vs tilt 10 min, 83 +/- 11 beats/min, difference not significant). Furthermore, during subsequent 20 +/- 5 months of disopyramide therapy, all but 1 patient remain asymptomatic. Thus, oral disopyramide may be effective for preventing inducible and spontaneous neurally mediated syncope.     

Autonomic responses to orthostatic stress in head-up tilt testing: Relationship to test-induced prolonged asystole

Background: Prolonged asystole is sometimes an extreme manifestation of neurally mediated syncope. Hypothesis: To investigate the mechanism of head-up tilt testing-induced prolonged (life-threatening) cardiac asystole, we measured temporal changes in frequency domain heart rate variability indices in 25 patients with syncope of undetermined etiology. Methods: Head-up tilt testing (80°) was performed in 25 patients for up to 40 min or until asystole or syncope occurred. Three patients (Group 1; 37 ±13 years, 1 man, 2 women) had an episode of prolonged cardiac asystole (≥ 10 s) during testing, necessitating cardiopulmonary resuscitation. Syncope, but no asystole, was induced in 10 patients (Group 2; 48 ± 31 years, 6 men, 4 women), and 12 patients (Group 3; 55 ± 20 years, 5 men, 7 women) failed to show asystole or syncope during testing. Power spectra of low (0.04–0.15 Hz) and high (0.15–0.40 Hz) frequency, and total (0.01–1.00 Hz) frequency spectra were measured in consecutive 2 min segments throughout the test. Results: Maximally changed values in heart rate, systolic blood pressure, and heart rate variability indices during testing were compared among the three groups (maximally changed values did not include the values during tilt-induced symptoms). High frequency spectra in Groups 2 and 3, but not in Group 1, decreased during the test. High frequency spectra, low frequency spectra, and total spectra in Group 1 were significantly higher than those in Groups 2 and 3 during testing. In Group 1 patients, findings at test-induced asystole were consistent with exaggerated sympathetic and concurrent persistent parasympathetic activity. Conclusion: Unusual autonomic responses to orthostatic stress can cause prolonged asystole, and this autonomic nerve dysregulation may relate to asystolic episodes associated with cardiovascular collapse.     

Hemodynamic significance of heart rate in neurally mediated syncope

BACKGROUND: Vasovagal and vasodepressor syncope are used interchangeably in the literature to describe the common faint syndrome, now collectively named neurally mediated syncope. The significance of heart rate (HR) in these reflex-induced reactions remains unclear. Hypothesis: The study was undertaken to investigate the hemodynamic significance of HR in tilt-induced neurally mediated syncope. METHODS: In all, 113 patients with syncope of unknown etiology were studied by head-up tilt test with invasive hemodynamic monitoring. Thirty-five patients (15 women, 20 men, age range 21 to 72 years) developed syncope and were enrolled for analysis. The hemodynamic data were compared between patients who developed bradycardia (vasovagal group, n = 15) and those without bradycardia (vasodepressor group, n = 20). RESULTS: The baseline hemodynamic data (mean +/- standard deviation) and the hemodynamic responses after 10-min headup tilt were similar between patients in the vasovagal and vasodepressor groups. During syncope, patients with vasovagal reaction developed hypotension and paradoxical bradycardia (HR = 52.4 +/- 5.9 beats/min), while patients with vasodepressor reaction developed a precipitous drop in arterial blood pressure with inappropriate HR (105 +/- 21 beats/min) compensation. Patients with vasovagal syncope manifested a significantly lower cardiac index and a significantly higher systemic vascular resistance index than patients with vasodepressor syncope (1.47 +/- 0.29 vs. 1.97 +/- 0.41 1/min/m2, p < 0.001 and 2098 +/- 615 vs. 1573 +/- 353 dynes x s x cm(-5) x m2, p < 0.003, respectively). A positive correlation existed between HR and cardiac index (r = 0.44, p = 0.008) during syncope in the patients studied. CONCLUSIONS: These findings suggest that the hemodynamic characteristics of vasovagal and vasodepressor reactions are different, and that HR plays a significant role in neurally mediated syncope.     

Reproducibility of asystole during head-up tilt testing in patients with neurally mediated syncope.

Tilt induced prolonged asystole has been considered to identify a distinct subgroup of patients with neurally mediated syncope and management including permanent pacemaker implantation has been suggested. To evaluate the reproducibility of asystolic response during head-up tilt testing (HUT), 33 patients with neurally mediated syncope and asystolic response (> or = 3 seconds) during HUT prospectively underwent two consecutive tests 13 +/- 15 days apart. On repeat tilt testing asystole was reproduced in 12 patients (36%), while 8 patients still had a positive HUT, but without asystole. Remarkably, 13 patients (40%) had a negative repeat HUT. Among 12 patients with asystole on both HUTs there was no significant difference in duration of asystole (14 371 +/- 11 430 ms vs 13 707 +/- 10 470 ms, P = ns) and time to syncope (36 +/- 20 min vs 37 +/- 20 min, P = ns) during initial and repeat HUTs. In conclusion, asystole during tilt testing does not seem to be a reproducible response.     

False positive head-up tilt: hemodynamic and neurohumoral profile

OBJECTIVES: This study examined differences in mechanisms of head-up tilt (HUT)-induced syncope between normal controls and patients with neurocardiogenic syncope. BACKGROUND: A variable proportion of normal individuals experience syncope during HUT. Differences in the mechanisms of HUT-mediated syncope between this group and patients with neurocardiogenic syncope have not been elucidated. METHODS: A 30-min 80 degrees HUT was performed in eight HUT-negative volunteers (Group I), eight HUT-positive volunteers (Group II) and 15 patients with neurocardiogenic syncope. Heart rate and blood pressure (BP) were monitored continuously. Epinephrine and norepinephrine plasma levels, as well as left ventricular dimensions and contractility determined by echocardiography, were measured at baseline and at regular intervals during the test. RESULTS: The main findings of this study were the following: 1) All parameters were similar at baseline in the three groups; and 2) During tilt: a) the time to syncope was shorter in Group III than in group II (9.5 +/- 3 vs. 17 +/- 3 min p < 0.05); b) there was an immediate, persisting drop in mean BP in Group III; c) the decrease rate of left ventricular end-diastolic dimensions was greater in Group III than in Group II or Group I (-1.76 +/- 0.42 vs. -0.87 +/- 0.35 and -0.67 +/- 0.29 mm/min, respectively, p < 0.05); d) the leftventricular shortening fraction was greater in Group III than in the other two groups (39 +/- 1 vs. 34 +/- 1 and 32 +/- 1%, respectively, p < 0.05); and e) although the norepinephrine level remained comparable among the groups, there was a significantly higher peak epinephrine level in Group III than in Group II and Group I (112.3 +/- 34 vs. 77.6 +/- 10 and 65 +/- 12 pg/ml, p < 0.05). CONCLUSIONS: Mechanisms of syncope during HUT appeared to be different in normal volunteers and patients with neurocardiogenic syncope. In the latter, there was evidence of an impaired vascular resistance response from the beginning of the orthostatic challenge. Furthermore, in the patients there was more rapid peripheral blood pooling, as indicated by the echocardiographic measurements of left ventricular end-diastolic changes, leading to more precocious symptoms. In syncopal patients, the higher level of plasma epinephrine probably mediated the increased cardiac contractility and possibly contributed to the impaired vasoconstrictive response.     

Endothelial function and peripheral vasomotion in the brachial artery in neurally mediated syncope

BACKGROUND: Paradoxical peripheral vasodilation is one of the suspected mechanisms of neurally mediated syncope. Parasympathetic stimulation following sympathetic activation during orthostatic stress mainly contributes to this vasodilation. HYPOTHESIS: Since endothelial function modulates peripheral vascular tone, this study aimed to determine whether endothelial function and inappropriate peripheral vasomotion has a significant role in the pathogenesis of neurally mediated syncope. METHODS: To investigate whether endothelial function is augmented or whether abnormal peripheral vasomotion exits, flow-mediated dilation (FMD, endothelium-dependent vasodilation) and sublingual glyceryl trinitrate-induced dilation (0.3 mg, GTN-D, endothelium-independent vasodilation) were measured in the brachial artery in 16 patients with neurally mediated syncope, aged 33 +/- 10 years, by using high-resolution ultrasound. All patients underwent positive head-up tilt testing. These measures were compared with those in 16 control subjects matched with the patients by age, gender, and coronary risk factors. For FMD, percent diameter changes were obtained from baseline to hyperemic conditions (1 min after 5 min occlusion of the forearm artery). There were five smokers in both the patient and the control groups, but there was no structural heart disease in either group. RESULTS: Baseline brachial artery diameters were comparable (3.8 +/- 0.6 vs. 3.8 +/- 0.7 mm, NS). Flow-mediated dilation in patients with neurally mediated syncope had a normal value of 9.8 +/- 5.0% despite the inclusion of five smokers. Flow-mediated dilation and GTN-D in patients with neurally mediated syncope were significantly greater than those in controls (9.0 +/- 5.0 vs. 3.0 +/- 3.5%, p<0.05; 18.4 +/- 5.5 vs. 14.1 +/- 4.4%, p<0.05). CONCLUSIONS: Augmented endothelial function and/or abnormal peripheral vasomotion in peripheral arteries are important in patients with neurally mediated syncope in selected populations.     

Tilt table testing in childhood: improved sensitivity by non-invasive haemodynamic monitoring devices?

OBJECTIVE: Tilt table testing represents a valuable diagnostic method in suspected neurally mediated syncope. As sympathovagal imbalance and impaired baroreceptor sensitivity (BRS) have been observed in these patients, both methods were used in this study to investigate whether a combination of these parameters would improve sensitivity and whether specific patterns of neurally mediated syncopes would correspond to characteristic trends in heart rate variability (HRV) and BRS. METHODS AND RESULTS: Fifty-one pts. (29 female, mean age 14.5 +/- 3.9 y) with unexplained syncope and 15 control subjects (9 female, mean age 14.8 +/- 3.0 y) were tested following a standard tilt table test protocol. Power spectral analysis (PSA) of HRV and BRS calculation were used additionally to beat-to-beat blood pressure and ECG-monitoring. Twenty-three out of 51 pts. (45%) experienced a syncope after 18 +/- 10.2 min of tilting. In 2/23 patients (8.6%) a postural tachycardia syndrome (POTS), in 14/23 (60.8%) a neurally mediated syncope of mixed type, in 2/23 (8.6%) a vasodepressor syncope and in 5/23 (21.7%) a cardioinhibitory syncope with asystole were observed. PSA of HRV and BRS revealed a specificity, sensitivity, and positive and negative predictive values of the cut-off points in combination (LF/HF > or = 2.7 and BRS > or = 8) of 93.3%, 65.2%, 93% and 39%, respectively. CONCLUSION: In this study population, BRS and PSA of HRV were able to improve sensitivity of tilt testing after unexplained syncope. Specific BRS or HRV patterns in different mechanisms of neurally mediated syncope could not be identified possibly due to the small sample size.     

Head-upright tilt-table testing in evaluation and management of the malignant vasovagal syndrome.

Vasovagally mediated cardiac asystole has been proposed as a potential cause of sudden cardiac death. To assess this possibility and identify characteristics that define patients with vasovagally mediated asystole, head-upright tilt-table testing was performed in 50 consecutive patients (26 women and 24 men, mean age 42 +/- 10 years) with recurrent unexplained syncope. The upright tilt-table test was performed in the fasting state for 30 minutes, with or without the use of intravenous isoproterenol (1 to 3 micrograms/min). The production of ventricular asystole lasting greater than 4 seconds was considered a positive result. All patients with tilt-induced asystole received therapy with either beta blockers, disopyramide, transdermal scopolamine or atrioventricular permanent pacing, the efficacy of which was evaluated with serial tilt-table tests. Reproducible tilt-induced asystole occurred in 10 patients (7 men and 3 women, mean age 23 +/- 12 years) (7 patients during baseline tilt, and 3 during isoproterenol infusion). Analysis of this group revealed that they had significantly more frequent and severe syncopal episodes (3 patients had episodes needing bystander cardiopulmonary resuscitation) than did those patients with tilt-induced syncope without asystole. All patients who had tilt-induced asystole eventually became tilt-table negative with therapy (4 with beta blockers, 2 with disopyramide, and 4 with atrioventricular permanent pacing), and over a mean follow-up of 21 +/- 6 months no further syncopal episodes occurred. It is concluded that patients with recurrent tilt-induced asystole represent a distinct subgroup that has recurrent severe syncope that may mimic or result in sudden cardiac death. Thus, the predischarge electrophysiologic study could predict late outcome with recurrence of preexicitation or supraventricular tachycardia in patients who had undergone surgical ablation of the accessory pathway with an overall predictive accuracy of 95% (107 of 113 patients), negative predictive value of 96% (103 of 107), and positive predictive value of 67% (4 of 6).     

Lack of association of heart rate variability parameters with head-up tilt-test responses in patients with syncope

BACKGROUND: Neurocardiogenic syncope is the most common type of syncope. Head-up tilt testing is the investigation of choice for diagnosis of patients with neurocardiogenic syncope. In this study, we aimed to findout any association between heart rate variability parameters and type of tilt-test response in patients with syncope. METHODS AND RESULTS: Forty-nine cases with unexplained syncopal attacks were enrolled into our study and were grouped according to the tilt-test responses. Tilt test was performed in all patients after excluding other causes of syncope. In case of a negative basal tilt-testing, pharmacological tilt testing was performed after 30 min of 5 mg sublingual isosorbide dinitrate. Holter monitoring was done from the beginning of tilt testing upto two hours post-procedure. The heart rate variability parameters analyzed were the mean of all coupling intervals between normal beats, the standard deviation about the mean of all coupling intervals between normal beats, the mean of all 5-min standard deviations of mean of all coupling intervals between normal beats, the proportion of adjacent normal R-R intervals differing by > 50 ms, the root mean square of the difference between successive RRs, and the standard deviation of 5-min mean of all coupling intervals between normal beats and ratio between low and high frequencies. CONCLUSIONS: In 35 patients, the tilt-test was positive, 16 were cardioinhibitor type (Group 1), four cases had a vasodepressor type response (Group 2) and 15 were mixed type (Group 3). Fourteen patients had a negative test result. The heart rate variability measures did not significantly differ among the study groups. The heart rate variability measures were compared between the tilt-test negative (Group 4) and the tilt-test positive groups (Groups 1, 2 and 3) and no statistically significant difference was found.     

Significance of circulatory epinephrine levels in exercise-induced neurally mediated syncope

BACKGROUND AND HYPOTHESIS: Previous research has failed to document temporal changes in epinephrine levels in patients with neurally mediated syncope associated with exercise. The purpose of this study was to investigate the role of circulatory catecholamines in exercise-induced neurally mediated syncope, specifically focusing on epinephrine levels. METHODS: The present study deals with temporal changes of circulatory catecholamine levels during head-up tilt tests (40 min, 80 degree tilt) in 62 patients with syncope of unknown origin, 7 of whom had syncope associated with exercise (exercise-induced group, 19+/-3 years). Data were compared with 10 control subjects (control group, 45+/-23 years). Of the 55 patients with syncope not associated with exercise, 32 tested positive for the head-up tilt tests (positive group, 31+/-16 years) and 23 patients tested negative (negative group, 46+/-19 years). Blood samples for circulatory catecholamine assay were obtained from the antecubital vein in the baseline supine position 2 min after the tilt started, every 10 min during tilt, and at the time of the onset of symptoms or the end of tilt. Levels of norepinephrine and epinephrine were determined using the high-pressure liquid chromatography (HPLC) method (pg/ml). RESULTS: Plasma norepinephrine levels among the four groups were similar at the supine position and during tilt testing. In contrast, patients in the exercise-induced group had significantly higher maximum epinephrine levels during head-up tilt testing than the other three groups (288+/-191 vs. 148+/-117, 66+/-31, and 54+/-27 pg/ml, respectively, p < 0.05). Patients in the positive group had higher maximum epinephrine levels than those in the negative group (p <0.05). Also, patients in the exercise-induced group and those in the positive group had a significantly shorter tilt-testing time than patients in the negative and control groups. CONCLUSIONS: A marked increase of epinephrine was observed during head-up tilt testing in patients with neurally mediated syncope associated with exercise. The present findings further accelerate the identification of the role of epinephrine in the mechanisms behind neurally mediated syncope associated with exercise.     

Hemodynamics of postmyocardial revascularization hypertension

The evolution of hemodynamic variables during the development of postcoronary bypass hypertension was investigated with use of serial cardiac output determination (indocyanine green dye) in 17 patients. Seven of the 17 patients remained normotensive (Group I) during the follow-up period of 4 to 6 hours after operation, whereas 10 (Group II) had a steady increase in blood pressure (173/101 mm Hg +/- 5.9/2.4 [mean +/- standard error] from 132/78 +/- 4.0/2.5 mm Hg immediately postoperatively, P less than 0.001) during the same time interval. Patients in Group I had no significant change in cardiac output, total peripheral resistance or heart rate. In contrast, patients who became hypertensive had a significant increase in total peripheral resistance (47 +/- 2.9 units/m2 from an initial level of 38 +/- 2.5 units/m2, P less than 0.001) with no significant change in cardiac index (2.73 +/- 0.17 versus 2.66 +/- 0.25 liters/min per m2, P greater than 0.10). Their heart rate, which was rapid initially (102 +/- 3.7 beats/min), remained unchanged during the hypertensive episode (103 +/- 3.0 beats/min). The mean rate of left ventricular ejection was not reduced by the increase in pressure and even tended to increase further in all but one patient. Central venous pressure (measured in all patients) and left atrial pressure (measured in eight patients) remained constant throughout the study in both Groups I and II. The results suggest that the mechanism underlying this type of hypertension is a generalized hemodynamic disturbance possibly related to overall sympathetic overdrive rather than the result of improved cardiac performance induced by myocardial revascularization.     

Positive head-up tilt table test in patients with the long QT syndrome.

AIMS: Syncope in patients with the long QT syndrome is commonly attributed to a ventricular arrhythmia (torsades de pointes). The susceptibility of patients with the long QT syndrome (LQTS) to neurally mediated syncope is currently unknown. METHODS AND RESULTS: Head-up tilt table testing (70 degrees) was performed in six patients with the long QT syndrome and a history of syncope. All patients had syncope with a mixed response. The RR interval was significantly decreased 2 min before the onset of syncope (980 +/- 125 ms vs 630 +/- 91 ms, P=0.003), and significantly increased during syncope (983.17 +/- 224.71; P=0.006). Non-significant changes in QT intervals were observed. Baseline QT was 513 +/- 86 ms and decreased to 450 +/- 59 ms 2 min before the onset of syncope (P=0.11). Although not statistically significant, QT intervals during syncope were longer than at 2 min before syncope (485 +/- 85 ms vs 450 +/- 59 ms; P=0.29). CONCLUSION: Our results suggest that patients with the LQTS are susceptible to neurally mediated syncope. Whether this susceptibility differs from control populations remains unresolved. From a clinical standpoint, neurocardiogenic syncope should be considered a diagnostic alternative in patients with LQTS.     

Distinct hemodynamic profiles in patients with vasovagal syncope: a heterogeneous population

OBJECTIVE: The objective was to investigate mechanisms of vasovagal syncope by identifying laboratory techniques that characterize cardiovascular profiles in patients with vasovagal syncope. BACKGROUND: The triggering mechanisms of vasovagal syncope are complex. The patient population is likely heterogeneous. We hypothesized that distinct hemodynamic profiles are definable with provocative maneuvers. METHODS: Three groups of subjects were matched for age and gender: 16 patients with a history of syncope and an inducible vasovagal response during passive tilt table testing (70 degrees, 45 min, group I), 16 with a history of syncope, negative passive tilt table testing but positive isoproterenol tilt table testing (0.05 microg/kg per min, 70 degrees, 10 min, group II), and 16 control subjects. Beat-to-beat hemodynamic functions were determined noninvasively by photo-plethysmography and impedance cardiography. RESULTS: At baseline, hemodynamic functions were not different among the three groups (supine). In response to tilt before any symptoms developed, total peripheral resistance decreased 9% +/- 14% in group I from baseline supine to tilt position but increased 27% +/- 18% in group II and 28% +/- 17% in controls (p < 0.001). Responses to isoproterenol were not significantly different between group II and controls in supine position. In response to tilt during isoproterenol infusion before any symptoms developed, total peripheral resistance decreased 24% +/- 20% in group II and increased 20% +/- 48% in controls (p = 0.002). CONCLUSIONS: Group I patients may have impaired ability to increase vascular resistance during orthostatic stress. The inability to overcome isoproterenol-induced vasodilatation during tilt is important in triggering a vasovagal response in group II patients. These data suggest that the population with vasovagal response is heterogeneous. Distinct hemodynamic profiles in response to various provocative maneuvers are definable with noninvasive, continuous monitoring techniques.     

Repeated tilt testing in patients with tilt-positive neurally mediated syncope.

In this study we have included 222 patients with apparent neurally mediated syncope and with a positive diagnostic tilt test. The mean age was 33.4+/-21.2 years (median 25.3): there were 107 men (median age 25.3) and 115 women (median age 22.6). The age difference between males and females was statistically significant (P = 0.002). The response to the diagnostic tilt test was: type 1 (mixed) in 74 patients; type 2A (cardioinhibitory and bradycardia) in 6; type 2B (cardioinhibitory and asystole) in 61; type 3 (vasodepressor) in 81. In all 222 patients the diagnostic tilt test was positive after 19+/-11 min (mean+/-SD), median time: 18 min. For the four types of syncope, the duration in minutes of the diagnostic tilt test was: type 1 (mixed) 19.5+/-11.4; type 2A (cardioinhibitory) 24.8+/-13.6; type 2B (cardioinhibitory and asystole) 14.7+/-10.2; type 3 (vasodepressor) 21.6+/-11.1. A significant difference was found between type 2B and type 3 responses (P = 0.002). Between males and females no significant differences in the duration of the diagnostic tilt test were found, neither for all responses, nor for the four subtypes. A type 2B (cardioinhibitory and asystole) response occurred in 61 patients. The duration of asystole was 12.8+/-10.6s (mean+/-SD; median 9, minimum 3, maximum 60). The head-up tilt test was repeated day after day: one session per day. The response became negative at the second session in 119 patients (54%); at session 3 in 47 (21%); at session 4 in 30 (13%); at session 5 in 15 (7%); at session 6 in 6 (3%); at session 7 in 2 (1%); at session 8 in 3 (1%). For all 222 patients the mean number of sessions in order to obtain a negative tilt test was 2.9 (SD 1.3; median 2). Only 25% of patients remained tilt-positive for three or more sessions. A negative tilt test was ultimately obtained in every patient. Follow-up data are available for 202/222 patients. The time span between the first and last tilt test was 11.1+/-10 months (median 8.8). Of these 202 patients, 163 remained free of any event (80.7%).     

Community hospital administration of intravenous tissue plasminogen activator in acute myocardial infarction: improved timing, thrombolytic efficacy and ventricular function

As an investigational fibrinolytic agent for acute myocardial infarction, intravenous recombinant tissue-type plasminogen activator (rt-PA) has been administered primarily in tertiary care and university centers. To determine the value of early initiation of such therapy, two satellite community hospital emergency rooms were established for use of rt-PA and the experience was compared among 142 consecutive patients who were transferred to a regional center for acute cardiac catheterization after intravenous rt-PA therapy. In Group I (n = 19), patients received rt-PA after interhospital transport to the regional center, but before cardiac catheterization. In Group II (n = 70), rt-PA therapy was initiated by the helicopter physician and nurse team after their arrival at the local community hospital emergency room. Group III patients (n = 53) had rt-PA administered in the local community hospital by the emergency room physician. Group III patients had earlier initiation of therapy (2.1 +/- 0.8 hours in Group III versus 3.8 +/- 1.2 hours in combined Groups I and II, p less than 0.001) and an increased rate of infarct vessel recanalization on the 90 minute coronary angiogram (81 in Group III versus 67% in combined Groups I and II, p = 0.057). The patients in Group III had a higher acute left ventricular ejection fraction (54 +/- 8% versus 50 +/- 9.5% in combined Groups I and II, p less than 0.01) and a trend toward an increased 7 day ejection fraction (55.5 +/- 9% versus 51.7 +/- 9.5%, respectively, p = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of heart failure on baroreflex control of sympathetic neural activity.

Baroreflex control of heart rate, vascular resistance and norepinephrine is impaired in patients with heart failure, but recent animal studies demonstrate preserved baroreflex control of sympathetic nerve activity in this disorder. Studies were therefore performed to compare baroreflex control of efferent sympathetic nerve activity to muscle in 10 normal subjects (age mean +/- SEM 21 +/- 1 years) and in 11 patients with moderate to severe heart failure (age 48 +/- 5 years, New York Heart Association class II to IV, left ventricular ejection fraction 19 +/- 2%, pulmonary capillary wedge pressure 27 +/- 2 mm Hg, cardiac index 2.04 +/- 0.22 liters/min/m2). Baroreflex activation was produced by intravenous infusion of phenylephrine (0.5 to 2.0 micrograms/kg/min) and deactivation by infusion of nitroprusside (0.4 to 2.5 micrograms/kg/min). During phenylephrine infusion, comparable increases in mean arterial pressure were produced in normal subjects (89 +/- 2 to 99 +/- 3 mm Hg, p less than 0.01) and in patients with heart failure (90 +/- 2 to 99 +/- 3 mm Hg, p less than 0.01). The patients with heart failure exhibited significantly attenuated (p less than 0.01 for normal vs heart failure) decreases in heart rate (93 +/- 5 to 90 +/- 6 beats/min, p = not significant [NS]) compared with normal subjects (67 +/- 3 to 58 +/- 4 beats/min, p less than 0.01) and tended to demonstrate attenuated sympathoinhibitory responses to this pressor stimulus. More strikingly, patients with heart failure demonstrated significant impairment of baroreflex responses during nitroprusside-induced baroreceptor deactivation. In normal subjects, nitroprusside produced a decrease in mean arterial (90 +/- 2 to 80 +/- 3 mm Hg, p less than 0.001) and right atrial (4 +/- 1 to 2 +/- 1 mm Hg, p less than 0.01) pressures with a resultant reflex increase in heart rate (68 +/- 3 to 81 +/- 4 beats/min, p less than 0.001) and muscle sympathetic nerve activity (326 +/- 74 to 746 +/- 147 U/min, p less than 0.01). In patients with heart failure (n = 10), nitroprusside produced comparable (p = NS for normal vs heart failure) decreases in mean arterial (89 +/- 2 to 77 +/- 2 mm Hg, p less than 0.001) and right atrial (6 +/- 1 to 1 +/- 1 mm Hg, p less than 0.001) pressures, but did not significantly alter heart rate (91 +/- 6 to 97 +/- 4 beats/min, p = NS) or sympathetic nerve activity (936 +/- 155 to 1179 +/- 275 U/min, p = NS).(ABSTRACT TRUNCATED AT 400 WORDS)     

Echocardiographic demonstration of decreased left ventricular dimensions and vigorous myocardial contraction during syncope induced by head-up tilt

Two-dimensional echocardiography was performed during a head-up tilt test in 11 control subjects (group I) and 18 patients with recurrent unexplained syncope. In four patients (group II), the head-up tilt test was negative at baseline and after isoproterenol infusion. Syncope was induced during baseline head-up tilt in nine patients (group III) and after isoproterenol challenge in five (group IV). The echocardiographic variables assessed were left ventricular end-systolic and end-diastolic areas and percent fractional shortening. At the end of head-up tilt, end-systolic area decreased by 4.5 +/- 1.3 and 3.0 +/- 1.2 cm2 in groups III and IV, respectively, compared with 0.5 +/- 0.7 and 0.2 +/- 0.1 cm2 in groups I and II, respectively (p less than 0.04). Similarly, end-diastolic area decreased by 5.5 +/- 2.6 cm2 in group III compared with 2.7 +/- 1.9 and 1.75 +/- 0.4 cm2 in group I and II, respectively (p less than 0.04). Additionally, at the end of the baseline study, fractional shortening was significantly greater in group III and group IV (43 +/- 5%) than in groups I and II (p less than 0.01). In conclusion, syncope induced by head-up tilt is associated with vigorous myocardial contraction and a significant decrease in left ventricular end-systolic dimensions. This left ventricular hypercontractility may play an important role in the pathogenesis of syncope induced by head-up tilt.     

Effect of cough on heart rate and blood pressure in patients with "cough syncope".

BACKGROUND: "Cough syncope" is uncommon, and its mechanism remains controversial. OBJECTIVES: This study evaluated susceptibility to cough-triggered neural reflex hypotension-bradycardia among cough syncope patients. We hypothesized that individuals with cough syncope would manifest not only more profound cough-triggered hypotension than do other fainters but also an inappropriate chronotropic response accompanying cough-induced hypotension, thereby supporting the notion that a neural reflex hypotension-bradycardia contributes to the condition. METHODS/RESULTS: Three patient groups were studied. Group 1 patients (n = 9) had "cough syncope." The remaining patients had recurrent faints of other causes: group 2 (n = 13) had a positive head-up tilt test, and group 3 (n = 18) had a negative tilt test. With cough, group 1 patients exhibited a greater drop in systolic pressure (-51 +/- 19.3 mmHg) than did either group 2 (-23 +/- 11.1 mmHg, P < .04) or group 3 patients (-28 +/- 12.4 mmHg, P < .05). Recovery time to normalization of systolic pressure was greater in group 1 (25 +/- 9.1 seconds) than in group 2 or 3 (8 +/- 2.7 seconds and 9 +/- 6.1 seconds, respectively, both P < .01 vs group 1). The expected positive chronotropic response accompanying cough-induced hypotension was diminished in group 1 patients (0.16 +/- 0.21 bpm/mmHg) compared with that in either group 2 (0.74 +/- 0.60 bpm/mmHg, P < .05 vs group 1) or group 3 (0.33 +/- 0.15 bpm/mmHg, P = .06 vs group 1). CONCLUSION: Cough syncope patients not only exhibit more pronounced hypotension in response to cough than other fainters, but they also manifest an inappropriate cough-triggered blood pressure-heart rate relationship. These findings argue in favor of the importance of a neurally mediated reflex contribution to symptomatic hypotension in cough syncope.     

An implantable loop recorder study of highly symptomatic vasovagal patients: the heart rhythm observed during a spontaneous syncope is identical to the recurrent syncope but not correlated with the head-up tilt test or adenosine triphosphate test.

OBJECTIVES: The aim of this study was to analyze the heart rhythm during spontaneous vasovagal syncope (VVS) in highly symptomatic patients with implantable loop recorders (ILR) and to correlate this rhythm with the heart rhythm observed during head-up tilt test (HUT). BACKGROUND: Heart rhythm obtained during provocative condition is often used to guide therapy in VVS. To date there is no conclusive evidence that the heart rhythm observed during a positive HUT can predict heart rhythm during VVS or that the heart rhythm observed during a spontaneous syncope will be identical to the recurrent syncope. METHODS: Twenty-five consecutive VVS patients (age 60.2 +/- 17.1 years; 14 women,) presenting with frequent syncopes (6.9 +/- 4.6 episodes/year) and a positive HUT (cardioinhibitory in 8 patients) were implanted with an ILR. Seven of them also had a positive adenosine triphosphate (ATP) test. RESULTS: Follow-up was 17.0 +/- 3.6 months. Thirty VVS were observed in 12 patients. Nine episodes showed bradycardia of <40 beats/min or asystole; progressive sinus bradycardia preceding sinus arrest was the most frequent electrocardiographic finding. Twenty-one syncopes occurred without severe bradycardia. The heart rhythm observed during the first syncope was identical to the recurrence. No correlation was found between slow heart rate at the ILR interrogation and a cardioinhibitory HUT response (p = 1.0) or a positive ATP test (p = 1.0). CONCLUSIONS: In highly symptomatic patients with VVS, the heart rhythm observed during spontaneous syncope does not correlate with the HUT. The heart rhythm during the first spontaneous syncope is identical to the recurrent syncope.     

Cardioinhibitory carotid sinus hypersensitivity predicts an asystolic mechanism of spontaneous neurally mediated syncope.

AIMS: We correlated the finding of cardioinhibitory carotid sinus hypersensitivity (CSH) with that observed during a spontaneous syncopal relapse by means of an implantable loop recorder (ILR). METHODS AND RESULTS: We included 18 consecutive patients with suspected recurrent neurally mediated syncope and positive cardioinhibitory response during carotid sinus massage (max pause 5.5 +/- 1.6 s) who had subsequent documentation of a spontaneous syncope by means of an ILR. They were compared with a 2:1 age- and sex-matched group of 36 patients with a clinical diagnosis of recurrent neurally mediated syncope and negative response to carotid sinus massage, tilt testing and ATP test. Asystole >3 s was observed at the time of the spontaneous syncope in 16 (89%) of CSH patients and in 18 (50%) of the control group (P = 0.007). Sinus arrest was the most frequent finding among CSH patients but not among controls (72 vs. 28%, P = 0.003). After ILR documentation, 14 CSH patients with asystole received dual-chamber pacemaker implantation; during 35 +/- 22 months of follow-up, 2 syncopal episodes recurred in 2 patients (14%), and pre-syncope occurred in another 2 patients (14%). Syncope burden decreased from 1.68 (95% confidence interval 1.66 - 1.70) episodes per patient per year before to 0.04 (0.038-0.042) after pacemaker implant (98% relative risk reduction). CONCLUSIONS: In patients with suspected neurally mediated syncope, the finding of cardioinhibitory CSH predicts an asystolic mechanism at the time of spontaneous syncope and, consequently, suggests a possible benefit of cardiac pacing therapy.