Elias Zarvalis

Provocation of Neurocardiogenic Syncope by Clomipramine Administration During the Head-Up Tilt Test in Vasovagal Syndrome

OBJECTIVES We sought to test the hypothesis that activation of the serotonergic system in patients with vasovagal syndrome during the head-up tilt test provokes syncope. BACKGROUND Central serotonergic activation participates in the pathogenesis of neurocardiogenic syncope. Drugs increasing serotonin (5-HT) in the central nervous system have not been tested as drug challenges during the head-up tilt test with clomipramine (Clom-HUT). METHODS The serotonergic re-uptake inhibitor clomipramine was infused (5 mg in 5 min) at the start of Clom-HUT in 55 patients (mean age 40 +/- 17 years) with a positive history of recurrent neurocardiogenic syncope and in 22 healthy control subjects (mean age 46 +/- 15 years). Blood samples were taken at 0, 5, 10 and 20 min for estimation of plasma prolactin and cortisol as neuroendocrine indicators of central serotonergic responsivity. All subjects had been previously tested with a basic 60 degrees head-up tilt test (B-HUT) for 30 min, and if negative, isoproterenol infusion was given at the end of the test. RESULTS Twenty-nine (53%) of the 55 patients and none of the 22 control subjects had a positive result in the B-HUT. With Clom-HUT, the proportion of patients who experienced a positive response increased to 80% (n = 44), although this happened to only one control subject. Prolactin and cortisol plasma levels increased significantly in the positive Clom-HUT patient group only. CONCLUSIONS The results indicate an increased responsivity of the central serotonergic neural system in subjects with vasovagal syndrome, the activation of which leads to sympathetic withdrawal. The use of clomipramine infusion with the tilt test seems to considerably improve its diagnostic value.

Central Serotonergic Responsiveness in Neurocardiogenic Syncope A Clomipramine Test Challenge

BACKGROUND Central serotonergic mechanisms appear to participate in the pathogenesis of recurrent neurally mediated syncope. The aim of the study was to investigate the responsiveness of the central serotonergic system by measuring the prolactin and cortisol responses to intravenous administration of the serotonin reuptake inhibitor clomipramine. METHODS AND RESULTS Twenty subjects free of any medical treatment were tested. Twelve had a history of recurrent syncopal attacks and positive tilt test (patient group, mean age 47+/-18 years, 8 men); 8 subjects without syncope and a negative tilt test result served as control subjects (mean age 49+/-10 years, 5 men). Twenty-five milligrams of clomipramine was administered intravenously within 15 minutes, and blood samples were taken at 0, 15, 30, 45, and 60 minutes. Two days later, a tilt test was performed at 60 degrees for 30 minutes and blood samples were taken at 0, 10, 20, and 30 minutes. During the clomipramine challenge, plasma prolactin levels increased in both groups. The levels at 30 minutes were higher in the patient group compared with the control group (17.3+/-7.2 vs 9.3+/-7.6 ng/mL, P=0.05). Similar results were observed for cortisol at 30 minutes (172+/-15 vs 118+/-21 ng/mL P=0. 04) and at 45 minutes (189+/-20 vs 116+/-23 ng/mL, P=0.03). The tilt test was positive in 8 (67%) out of 12 of the patient group and negative in all control subjects. In the samples taken during the tilt test, significant increases in prolactin and cortisol were observed only in the subjects with positive tilt test results. CONCLUSIONS Patients with a history of neurocardiogenic syncope show a higher responsiveness of the central serotonergic system to clomipramine challenge. The results support the view that central serotonergic mechanisms are involved in the pathophysiology of the syndrome.

Hormonal Responses During Tilt-Table Test in Neurally Mediated Syncope

The hormonal profile during tilt testing was examined in syncopal patients. An increase in the growth hormones cortisol and prolactin was found during syncope, suggesting an implication of central serotonergic activation.

Absence of Effects of Short-Term Estrogen Replacement Therapy on Resting and Exertional QT and QTc Dispersion in Postmenopausal Women with Coronary Artery Disease

Women, on average, have a longer QT interval on the electrocardiogram and are at higher risk of developing torsade de pointes from antiarrhythmic therapy than men. Although endogenous estrogen may play a role in these sex differences, the effect of estrogen replacement therapy has not been examined. Ten women, 65 ± 7 years of age, wit/i stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease (at least one ≥ 70%) stenosis were studied. All women had been postmenopausal for at least 1 year, and none had ever received hormone replacement therapy (HRT). The patients received standard dose HRT (0.625 mg/day oral conjugated estrogen) or matching placebo for 4 weeks in random order, with crossover after a 4‐week washout period. Exercise testing using the standard Bruce protocol was performed at the end of the first and third months of the study. Antianginal medications remained unchanged throughout the study period. Compared to placebo, HRT caused a significant increase in plasma estradiol levels from 5.55 ± 1.66 to 31.11 ± 14.95 pg/mL (P = 0.001). QT and QTc, as well as QT and QTc dispersion, did not differ at rest and at peak exercise between the two exercise tests. Likewise, other test results, including angina score, exercise time, ST‐T changes, blood pressure, heart rate, and double product were unchanged. Short‐term HRT did not alter cardiac repolarization at rest and during exercise in postmenopausal women with known coronary disease.

Baroreflexes in Vasovagal Syncope: Two Types of Abnormal response

FLEVARI, P.P., et al.: Baroreflexes in Vasovagal Syncope: Two Types of Abnormal Response. Heart rate changes to hypotensive stimuli (baroreceptor sensitivity [BRS]) and forearm blood flow (FBF) reduction during head‐up tilt are mediated by arterial and cardiopulmonary baroreceptors. Regarding baroreflexes in neurocardiogenic syncope (NCS), an apparent variation exists in findings reported in the literature. This may be due to the existence of different types of response. This study included 39 patients with NCS and positive tilt test and 26 normal subjects with negative test. Patients were grouped according to the type of tilt test response (mixed, cardioinhibitory, vasodepressor). BRS was noninvasively assessed in the supine position as an estimate of arterial baroreceptor sensitivity. As an estimate of cardiopulmonary baroreceptor reactivity, FBF was measured by venous occlusion plethysmography in the supine position and every 2.5 minutes during the first 15 minutes of tilt. BRS was related to percent of FBF changes. BRS was impaired in syncopal patients relative to controls (7.2 ± 0.9 vs 10.4 ± 0.3 ms/mmHg, P = 0.01), especially in vasodepressive type (4.9 ± 1.0 ms/mmHg, P = 0.0001). FBF changes during tilt were subnormal in NCS, ascribed to two different patterns: one, characterized by impaired vasoconstriction (FBF during tilt showing < 10% mean reduction relative to baseline, especially in vasodepressive type) and another, characterized by a great variability across time (unstable response, especially in cardioinhibitory type). In controls, BRS was related to the percent of FBF changes after 2.5, 5, and 10 minutes of tilt (P values 0.0001, 0.004, and 0.008). In patients, BRS was uncoupled from FBF changes. In conclusion, baroreflexes in NCS are impaired, unstable, and disorganized. Impairment predominates in the vasodepressive type and instability in the cardioinhibitory. The results of this study are indicative of more than one baroreflex‐mediated response types.

Situational syncope: response to head-up tilt testing and follow-up: comparison with vasovagal syncope.

Among sequential patients with neurally‐mediated syncope, we studied the response to head‐up tilt test (HUTT) in patients with situational syncope (SS) and their follow‐up. Our findings were compared to those in patients with vasovagal syncope (VVS). The response to HUTT in patients with SS has not to date been fully investigated. Additionally, the prognosis of SS patients has not been systematically studied. We studied 162 consecutive patients with recurrent SS or VVS, all free of structural heart disease. Before study inclusion, they underwent an HUTT and were followed up for 12 months. Patients with SS were advised to avoid the trigger event. Patients with VVS were treated with propranolol or fluoxetine. For each patient we compared the number of syncopal spells during the last 12 months before study inclusion with that during follow‐up. Among the 162 patients, 36 had SS and 126 had VVS. The response to HUTT and the number of syncopes before and during follow‐up were similar in both groups. Among patients with SS, 10 (28%) had also experienced occasional episodes of VVS; however, they had a similar response to HUTT and prognosis to the remaining 26 SS patients without VVS attacks. Patients with SS have a similar response to HUTT and similarly benign clinical course to patients with VVS. The coexistence of occasional VVS episodes in patients with SS is not associated with a higher rate of positive HUTT or worse prognosis. (PACE 2004; 27:918–923)

Effect of rotational coronary atherectomy on peripheral endothelin-1, atrial natriuretic peptide, and cyclic adenosine monophosphate plasma levels.

We investigated the effects of coronary rotational atherectomy (PTCRA) on plasma levels of endothelin-1 (ET-1), atrial natriuretic peptide (ANP), and cyclic adenosine monophosphate (cAMP). We studied 14 patients undergoing PTCRA and compared them with 14 patients undergoing plain balloon angioplasty. Blood samples were taken from the femoral vein at baseline, after the end of the atherectomy, after the first balloon inflation, after the end of the procedure, and 4 hours later. ET-1 increased in the angioplasty group from 6.3 ± 3.2 pmol/L at baseline to 8.5 ± 3.9 pmol/L at the end of the procedure (F = 3.83, P = .02), whereas it did not change in the PTCRA group. ANP increased in the PTCRA group from 78.1 ± 15.7 pmol/L at baseline to 89.7 ± 24.0 pmol/L at the end of the procedure (F = 6.75, P = .0001), whereas it did not change in the angioplasty group. cAMP decreased in the PTCRA group, whereas it did not change in the angioplasty group. In conclusion, ET-1 increases less, ANP increases more, and cAMP decreases more during atherectomy than during plain balloon angioplasty.

Incessant Ventricular Tachycardia Associated with Congestive Heart Failure

A 31-year-old male was referred to our department with dyspnea on minimal exertion. He gave a 6-month history of rapid, regular palpitations, lasting for minutes to several hours. They became progressively longer in duration, and 2 weeks prior to his admission they became incessant. He denied dizziness or loss of consciousness, but he complained of rapidly worsening dyspnea on exertion for the preceding 2 months. On admission, he was in incessant tachycardia with signs of congestive heart failure. A 12-lead ECG indicated ventricular tachycardia with a right bundle branch block, right axis deviation morphology, at a rate of 140 beats/min. Hematology and blood biochemistry wore within normal limits. Antibody titers against common viruses did not indicate recent viral infection. Chest X ray showed cardiomegaly with upper lobe blood diversion and perihilar edema. Echocardiography showed a dilated, globally hypokinetic left ventricle, with an ejection fraction of approximately 35% (Fig. 1). Coronary angiography showed normal coronary arteries.