Prognostic value of strain by feature-tracking cardiac magnetic resonance in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by ventricular dysfunction and ventricular arrhythmias (VA). Adequate arrhythmic risk assessment is important to prevent sudden cardiac death. We aimed to study the incremental value of strain by feature-tracking cardiac magnetic resonance imaging (FT-CMR) in predicting sustained VA in ARVC patients. METHODS AND RESULTS: CMR images of 132 ARVC patients (43% male, 40.6 ± 16.0 years) without prior VA were analysed for global and regional right and left ventricular (RV, LV) strain. Primary outcome was sustained VA during follow-up. We performed multivariable regression assessing strain, in combination with (i) RV ejection fraction (EF); (ii) LVEF; and (iii) the ARVC risk calculator. False discovery rate adjusted P-values were given to correct for multiple comparisons and c-statistics were calculated for each model. During 4.3 (2.0-7.9) years of follow-up, 19% of patients experienced sustained VA. Compared to patients without VA, those with VA had significantly reduced RV longitudinal (P ≤ 0.03) and LV circumferential (P ≤ 0.04) strain. In addition, patients with VA had significantly reduced biventricular EF (P ≤ 0.02). After correcting for RVEF, LVEF, and the ARVC risk calculator separately in multivariable analysis, both RV and LV strain lost their significance [hazard ratio 1.03-1.18, P > 0.05]. Likewise, while strain improved the c-statistic in combination with RVEF, LVEF, and the ARVC risk calculator separately, this did not reach statistical significance (P ≥ 0.18). CONCLUSION: Both RV longitudinal and LV circumferential strain are reduced in ARVC patients with sustained VA during follow-up. However, strain does not have incremental value over RVEF, LVEF, and the ARVC VA risk calculator.

Sports in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy and desmosomal mutations.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a rare cardiomyopathy associated with life-threatening arrhythmias and an increased risk of sudden cardiac death. In addition to mutations in desmosomal genes, environmental factors such as exercise and sport have been implicated in the pathogenesis of the disease. Recent studies have shown that exercise may be associated with adverse outcomes in patients with ARVD/C. On the basis of current evidence, patients with ARVD/C are recommended to limit exercise irrespective of their mutation status. Some studies have suggested the presence of an entirely acquired form of the disease caused by exercise, which has been dubbed "exercise-induced ARVD/C."

Neurally mediated hypotension in systemic lupus erythematosus patients with fibromyalgia.

OBJECTIVE: Fibromyalgia (FM) is a major determinant of poor health status in systemic lupus erythematosus (SLE). FM has been shown to be associated with neurally mediated hypotension (NMH) in the general population, in which effective treatments exist. We explored whether NMH was more common in SLE patients with FM than those without. METHODS: Seventy-six SLE patients (4 male, 72 female; 1 ethnic Indian, 28 African American, 47 Caucasian; mean age 40.2 +/- 9.4 yr) were recruited and their FM status ascertained using American College of Rheumatology (ACR) classification criteria. Patients who were pregnant or deconditioned were excluded. A two-stage tilt-table test was used to detect NMH. All patients completed the SF-36 Heath Status Inventory (SF-36) and the Krupp Fatigue Severity Scale (KFSS) to evaluate their quality of life. Serological markers and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were recorded. Medications that might interfere with testing were temporarily withheld before the tilt-table test. RESULTS: The prevalence of NMH (first stage) in SLE patients was 47.9%. Seven patients had both NMH and postural orthostatic tachycardia syndrome. Two patients had borderline results with symptoms reproduced but an inadequate drop in systolic blood pressure by definition (a drop of at least 25 mmHg defines an abnormal response). Eighteen (23.7%) SLE patients had FM and 51 (67.1%) had at least one tender point (TP). The frequency of NMH (first or second stage) in SLE with FM was 58.3% compared with 69.4% in SLE without FM (odds ratio 0.62, 95% CI 0.16-2.37). SF-36 and KFSS scores were not significantly different in SLE patients with and without NMH. However, both scores were found to be associated with FM status (P<0.001 and P = 0.014), reflecting poor health status in the FM group. No confounding variable was found to be significantly associated with both NMH and FM. CONCLUSION: NMH is common in SLE patients with a high prevalence rate. The large increase in NMH, a form of autonomic neuropathy, in SLE, has not been explained. However, NMH has no impact on quality of life above that determined by FM, and has no statistically significant association with FM status. Identification of NMH may be important in selected patients with SLE who have chronic fatigue, but NMH cannot explain the increased prevalence of FM in SLE.

Guías actualizadas de la ACC/AHA para evaluación cardiovascular perioperatoria para cirugía no cardiaca / Actualized guidelines of the ACC/AHA for perioperative cardiovascular evaluation to no cardiac surgery

Estas guías representan una actualización de aquellos publicados en 1996 dirigidas a médicos que están comprometidos en el cuidado preoperatorio, operatorio y postoperatorio de pacientes que van a cirugía no cardiaca. Ellas proveen un marco de referencia para analizar el riesgo cardiaco de cirugia no cardiaca en una variedad de pacientes y situaciones quirúrgicas. El tema principal de estas guías es que la intervención preoperatoria es raramene necesaria simplemente para disminuir el riesgo de la cirugía a menos que dicha intervención sea indicada independiente del contexto preoperatorio.

Laser ablation of the pulmonary veins by using a fiberoptic balloon catheter: implications for treatment of paroxysmal atrial fibrillation.

BACKGROUND AND OBJECTIVE: Focal sources of paroxysmal atrial fibrillation may be treatable by electrical isolation of the pulmonary veins from the left atrium. A new fiberoptic balloon catheter was tested as an alternative to radiofrequency catheter ablation for creation of circumferential thermal lesions at the pulmonary vein orifice. STUDY DESIGN/MATERIALS AND METHODS: In vitro and in vivo experiments were conducted in canine hearts to demonstrate efficacy and optimize ablation dosimetry. Continuous-wave, 1.06-microm, Nd:YAG laser radiation was delivered radially through diffusing optical fiber tips enclosed in a balloon catheter. During in vivo studies, the catheter was placed at the pulmonary vein orifice through a left atrial appendage sheath under X-ray fluoroscopic guidance during an open-chest procedure. Additionally, circumferential lesions in the left atrial appendage were correlated with epicardial electrograms demonstrating elimination of electrical activity. RESULTS: The pulmonary veins were successfully ablated by using laser powers of 30--50 W and irradiation times of 60--90 seconds. Transmural, continuous, and circumferential lesions were produced in the pulmonary veins in a single application without evidence of tissue vaporization or endothelial disruption. CONCLUSION: Laser ablation by using a fiberoptic balloon catheter may represent a promising alternative to radiofrequency catheter ablation for electrical isolation of the pulmonary veins from the left atrium during treatment of paroxysmal atrial fibrillation. Further development and testing of the fiberoptic catheter is warranted for possible clinical studies.

Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome: a randomized controlled trial.

CONTEXT: Patients with chronic fatigue syndrome (CFS) are more likely than healthy persons to develop neurally mediated hypotension (NMH) in response to prolonged orthostatic stress. OBJECTIVE: To examine the efficacy of fludrocortisone acetate as monotherapy for adults with both CFS and NMH. DESIGN: Randomized, double-blind, placebo-controlled trial conducted between March 1996 and February 1999. SETTING: Two tertiary referral centers in the United States. PATIENTS: One hundred individuals aged 18 to 50 years who satisfied Centers for Disease Control and Prevention criteria for CFS and had NMH provoked during a 2-stage tilt-table test. Eighty-three subjects had adequate outcome data to assess efficacy. INTERVENTION: Subjects were randomly assigned to receive fludrocortisone acetate, titrated to 0.1 mg/d (n = 50) or matching placebo (n = 50) for 9 weeks, followed by 2 weeks of observation after discontinuation of therapy. MAIN OUTCOME MEASURE: Proportion of subjects in each group with at least a 15-point improvement on a 100-point global wellness scale. RESULTS: Baseline demographic and illness characteristics between the groups were similar; CFS had been present for at least 3 years in 71%. Using an intention-to-treat analysis, 7 subjects (14%) treated with fludrocortisone experienced at least a 15-point improvement in their wellness scores compared with 5 (10%) among placebo recipients (P =.76). No differences were observed in several other symptom scores or in the proportion with normal follow-up tilt test results at the end of the treatment period. CONCLUSIONS: In our study of adults with CFS, fludrocortisone as monotherapy for NMH was no more efficacious than placebo for amelioration of symptoms. Failure to identify symptomatic improvement with fludrocortisone does not disprove the hypothesis that NMH could be contributing to some of the symptoms of CFS. Further studies are needed to determine whether other medications or combination therapy are more effective in treating orthostatic intolerance in patients with CFS.

Linear lesions in myocardium created by Nd:YAG laser using diffusing optical fibers: in vitro and in vivo results.

BACKGROUND AND OBJECTIVE: Linear lesions may be necessary for successful catheter ablation of cardiac arrhythmias such as atrial fibrillation. This study uses laser energy delivered through diffusing optical fibers as an alternative to radiofrequency energy for the creation of linear lesions in cardiac tissue in a single application. STUDY DESIGN/MATERIALS AND METHODS: Samples of canine myocardium were placed in a heated, circulating saline bath and irradiated with a 1.06-microm, continuous-wave Nd:YAG laser during in vitro studies. Laser ablation was then performed in vivo on the epicardial surface of the right ventricle during an open-chest procedure by using similar ablation parameters. Laser energy was delivered to the tissue by being diffused radially through flexible optical fiber tips oriented parallel to the tissue surface. Histology and temperature measurements verified transmurality, continuity, and linearity of the lesions. RESULTS: Peak tissue temperatures measured in vitro remained low (51 +/- 1 degrees C at the endocardial surface, 61 +/- 6 degrees C in the mid-myocardium, and 55 +/- 6 degrees C at the epicardial surface) with no evidence of tissue charring or vaporization. Lesion dimensions produced in vitro and in vivo were similar (depth, 6 mm; width, 8-10 mm; length, 16-22 mm), demonstrating that tissue perfusion in vivo did not significantly alter the heating. CONCLUSION: Long linear lesions, necessary for duplication of the surgical maze procedure during catheter ablation of atrial fibrillation, may be created by using laser radiation delivered through flexible diffusing optical fiber tips. Further development of steerable catheters for endocardial atrial ablation and studies correlating thermal damage zones with electrophysiologic indicators of irreversible conduction block are warranted.

Temporal repolarization lability in hypertrophic cardiomyopathy caused by beta-myosin heavy-chain gene mutations.

BACKGROUND: Certain genetic mutations associated with hypertrophic cardiomyopathy (HCM) carry an increased risk of sudden death. QT variability identifies patients at a high risk for sudden death from ventricular arrhythmias. We tested whether patients with HCM caused by beta-myosin heavy-chain (beta-MHC) gene mutations exhibit labile ventricular repolarization using beat-to-beat QT variability analysis. METHODS AND RESULTS: We measured the QT variability index and heart rate-QT interval coherence from Holter monitor recordings in 36 patients with HCM caused by known beta-MHC gene mutations and in 26 age- and sex-matched controls. There were 7 distinct beta-MHC gene mutations in these 36 patients; 9 patients had HCM caused by the malignant Arg(403)Gln mutation and 8 patients had HCM caused by the more benign Leu(908)Val mutation. The QT variability index was higher in HCM patients than in controls (-1.24+/-0.17 versus -1. 58+/-0.38, P<0.01), and the greatest abnormality was detected in patients with the Arg(403)Gln mutation (-0.99+/-0.49 versus -1. 46+/-0.43 in controls, P<0.05). In keeping with this finding, coherence was lower for the entire HCM group than for controls (P<0. 001). Coherence was also significantly lower in patients with the Arg(403)Gln mutation compared with controls (P<0.05). CONCLUSIONS: These findings suggest that (1) patients with HCM caused by beta-MHC gene mutations exhibit labile repolarization quantified by QT variability analysis and, hence, may be more at risk for sudden death from ventricular arrhythmias, and (2) indices of QT variability may be particularly abnormal in patients with beta-MHC gene mutations that are associated with a poor prognosis.

Pharmacologic approaches to therapy for vasovagal syncope.

Vasovagal syncope is a common disorder of autonomic cardiovascular regulation. Many pharmacologic agents have been proposed as effective in the management of this condition based on nonrandomized clinical trials. Notably, only 3 agents--atenolol, midodrine, and paroxetine--have demonstrated efficacy in the treatment of vasovagal syncope in at least 1 prospective, randomized, placebo-controlled clinical trial. Other therapies commonly used in treating syncope include increased salt and fluid intake and fludrocortisone. In this review, we provide a summary of currently available data that support or question the use of various pharmacologic agents for treatment of vasovagal syncope.

Putting it together: a new treatment algorithm for vasovagal syncope and related disorders.

The consensus process that culminated in this symposium established an algorithm to guide the diagnosis and treatment of patients with vasovagal syncope and related disorders. In some patients, the hemodynamic response to standing may identify an abnormality-postural orthostatic tachycardia syndrome or orthostatic hypotension-that can often be treated without further testing. When the response to standing is normal, tilt-table testing may be useful in making the diagnosis of vasovagal syncope and guiding treatment. In some patients, however, the diagnosis is clear from the history, and tilt-table testing may not be necessary. Not all patients with vasovagal syncope need to be treated, and many can be treated effectively with education, reassurance, and a simple increase in dietary salt. In evaluating the results of tilt-table testing, an important consideration is the distinction between vasovagal syncope and the dysautonomic response to tilt characterized by a gradual and progressive decrease in blood pressure that leads to syncope. Current practice patterns suggest that beta blockers, fludrocortisone, and midodrine, are commonly used to treat patients with vasovagal syncope, and patients with the dysautonomic response are generally treated with fludrocortisone and midodrine. Permanent pacing with specialized pacing algorithms should be considered for patients with frequent vasovagal syncope that is refractory to medical therapy. The guidelines proposed here are an amalgam of clinical experience, expert opinion, and research evidence; however, they do not suggest a standard of care for all patients.

Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome.

OBJECTIVE: To report chronic fatigue syndrome (CFS) associated with both Ehlers-Danlos syndrome (EDS) and orthostatic intolerance. STUDY DESIGN: Case series of adolescents referred to a tertiary clinic for the evaluation of CFS. All subjects had 2-dimensional echocardiography, tests of orthostatic tolerance, and examinations by both a geneticist and an ophthalmologist. RESULTS: Twelve patients (11 female), median age 15.5 years, met diagnostic criteria for CFS and EDS, and all had either postural tachycardia or neurally mediated hypotension in response to orthostatic stress. Six had classical-type EDS and 6 had hypermobile-type EDS. CONCLUSIONS: Among patients with CFS and orthostatic intolerance, a subset also has EDS. We propose that the occurrence of these syndromes together can be attributed to the abnormal connective tissue in dependent blood vessels of those with EDS, which permits veins to distend excessively in response to ordinary hydrostatic pressures. This in turn leads to increased venous pooling and its hemodynamic and symptomatic consequences. These observations suggest that a careful search for hypermobility and connective tissue abnormalities should be part of the evaluation of patients with CFS and orthostatic intolerance syndromes.

Management of vasovagal syncope.

Vasovagal syncope is a common disorder of autonomic cardiovascular regulation that can be very disabling and result in a significant level of psychosocial and physical limitations. The optimal approach to treatment of patients with vasovagal syncope remains uncertain. Although many different types of treatment have been proposed and appear effective based largely on small nonrandomized studies and clinical series, there is a remarkable absence of data from large prospective clinical trials. However, based on currently available data, the pharmacologic agents most likely to be effective in the treatment of patients with vasovagal syncope include beta blockers, fludrocortisone, and alpha-adrenergic agonists. In this article, we provide a summary of the various therapeutic options that have been proposed for vasovagal syncope and review the clinical studies that form the basis of present therapy for this relatively common entity.

Neurally mediated hypotension and chronic fatigue syndrome.

A substantial body of clinical evidence now supports an association between various forms of hypotension and both idiopathic chronic fatigue and the chronic fatigue syndrome (CFS). Patients with CFS have a high prevalence of neurally mediated hypotension, and open treatment of this autonomic dysfunction has been associated with improvements in CFS symptoms. Randomized trials are now in progress to evaluate the efficacy of treatments directed at neurally mediated hypotension in those with CFS patients, and the results of these trials should help guide more basic inquiries into the mechanisms of orthostatic intolerance in affected individuals.

Beat-to-beat repolarization lability identifies patients at risk for sudden cardiac death.

INTRODUCTION: Recent studies have implicated repolarization lability in the genesis of malignant ventricular arrhythmias. However, few data exist on assessment of temporal QT interval variability and its relation to arrhythmogenesis. We tested the ability of the QT variability index (QTVI), a measure of beat-to-beat QT interval fluctuations measured on a single ECG lead, to identify patients presenting with malignant ventricular arrhythmias and predict their subsequent occurrences. METHODS AND RESULTS: We measured the QTVI in 95 patients presenting for electrophysiologic study (EPS). The ability of the QTVI to identify patients with sudden cardiac death (SCD) or sustained monomorphic ventricular tachycardia (MVT) on presentation and during follow-up of 23.7+/-14.3 months was compared with spatial QT dispersion, T wave alternans ratio during atrial pacing, MVT inducibility at EPS, signal-averaged ECG, heart rate variability, and ejection fraction. The QTVI was higher in patients with heart disease than in controls (-0.7+/-0.7 vs -1.1+/-0.5, P < 0.05), and higher in patients presenting with SCD than in other patients with heart disease (0.0+/-0.6 vs -0.8+/-0.5, P < 0.05). The QTVI was the only clinical variable that identified patients who presented with SCD (P = 0.004, odds ratio = 12.5) on stepwise, logistic multiple regression. Fourteen patients had arrhythmic events during follow-up. In a Kaplan-Meier analysis of arrhythmic events, QTVI> or =0.1 was a discriminator for higher risk of arrhythmic events (P < 0.05). CONCLUSIONS: (1) This noninvasive measure of temporal repolarization lability identified patients with SCD and predicted arrhythmia-free survival. (2) Further studies are needed to determine the mechanisms that mediate beat-to-beat QT interval variability.

Comparison of adenosine effects on atrioventricular node reentry and atrioventricular reciprocating tachycardias.

BACKGROUND: Adenosine is an established first line therapy for the treatment of narrow complex tachycardias. The two most common etiologies of paroxysmal supraventricular tachycardia (SVT) are atrioventricular node reentry tachycardia (AVNRT) and atrioventricular reciprocating tachycardia (AVRT). HYPOTHESIS: We postulated that adenosine might have different effects on the termination of AVNRT vs. AVRT, and that these differences might assist in the noninvasive differentiation between these diagnoses. METHODS: Fifty-nine patients referred for the diagnosis and treatment of SVT were included in the study. All patients had SVT induced during electrophysiology testing, and each patient received adenosine during SVT. The adenosine dose, time to tachycardia termination, and site of tachycardia termination were recorded. Seventeen patients required isoproterenol administration to initiate SVT. This subset of patients was compared with those not requiring isoproterenol. RESULTS: There was no statistically significant difference in the adenosine dose or time to tachycardia termination when comparing patients with AVNRT with those with AVRT. All patients with AVNRT had termination of tachycardia in the antegrade direction with final activation in the atria. Patients requiring isoproterenol for tachycardia initiation experienced tachycardia termination significantly faster than those not requiring isoproterenol, although there was no difference in the dose of adenosine required for termination. CONCLUSION: These data demonstrate that patients with dual AV node physiology and AVNRT do not have altered sensitivity to adenosine compared with patients with AVRT and normal AV nodes. Further investigation will be required to determine the clinical utility of the significantly shorter time to tachycardia termination for patients receiving isoproterenol.

Predictors of fluoroscopy time and estimated radiation exposure during radiofrequency catheter ablation procedures.

The objective of this study was to identify factors that predict fluoroscopy duration and radiation exposure during catheter ablation procedures. The patient population included 859 patients who participated in the Atakr Ablation System clinical trial at 1 of 9 centers (398 male and 461 female patients, aged 36 +/- 21 years). Each patient underwent catheter ablation of an accessory pathway, the atrioventricular junction, or atrioventricular nodal reentrant tachycardia using standard techniques. The duration of fluoroscopy was 53 +/- 50 minutes. Factors identified as independent predictors of fluoroscopy duration included patient age and sex, the success or failure of the ablation procedure, and the institution at which the ablation was performed. Catheter ablation in adults required longer fluoroscopy exposure than it did in children. Men required longer durations of fluoroscopy exposure than did women. The mean estimated "entrance" radiation dose was 1.3 +/- 1.3 Sv. The dose needed to cause radiation skin injury was exceeded during 22% of procedures. The overall mean effective absorbed dose from catheter ablation procedures was 0.025 Sv for female patients and 0.017 Sv for male patients. This degree of radiation exposure would result in an estimated 1,400 excess fatal malignancies in female patients and 2,600 excess fatal malignancies in male patients per 1 million patients.

Beat-to-beat QT interval variability: novel evidence for repolarization lability in ischemic and nonischemic dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is associated with a high incidence of malignant ventricular arrhythmias and sudden death. Abnormalities in repolarization of ventricular myocardium have been implicated in the development of these arrhythmias. Spatial heterogeneity in repolarization has been studied in DCM, but temporal fluctuations in repolarization in this setting have been largely ignored. We sought to test the hypothesis that beat-to-beat QT interval variability is increased in DCM patients compared with control subjects. METHODS AND RESULTS: Eighty-three patients with ischemic and nonischemic DCM and 60 control subjects served as the study population. Beat-to-beat QT interval variability was measured by automated analysis on the basis of 256-second records of the surface ECG. A QT variability index (QTVI) was calculated for each subject as the logarithm of the ratio of normalized QT variance to heart rate variance. The coherence between heart rate and QT interval fluctuations was determined by spectral analysis. In patients, ejection fractions were assessed by echocardiography or ventriculography, and spatial QT dispersion was determined from the standard 12-lead ECG. DCM patients had greater QT variance than control subjects (60.4+/-63.1 versus 25.7+/-24.8 ms2, P<.0001) despite reduced heart rate variance (6.7+/-7.8 versus 10.5+/-10.4 bpm2, P=.01). The QTVI was higher in DCM patients than in control subjects, with a high degree of significance (-0.43+/-0.71 versus -1.29+/-0.51, P<10[-12]). QTVI did not correlate with ejection fraction or spatial QT dispersion but did depend on New York Heart Association functional class. QTVI did not differ between DCM patients with ischemic and those with nonischemic origin. Coherence between heart rate and QT interval fluctuations at physiological frequencies was lower in DCM patients compared with control subjects (0.28+/-0.14 versus 0.39+/-0.18, P<.0001). CONCLUSIONS: DCM is associated with beat-to-beat fluctuations in QT interval that are larger than normal and uncoupled from variations in heart rate. QT interval variability increases with worsening functional class but is independent of ejection fraction. These data indicate that DCM leads to temporal lability in ventricular repolarization.

Acute radiation dermatitis following radiofrequency catheter ablation of atrioventricular nodal reentrant tachycardia.

Radiation exposure during fluoroscopic imaging poses potential risks to patients and physicians, especially during protracted cardiovascular or radiological interventional procedures. We describe a woman with refractory paroxysmal supraventricular tachycardia who underwent radiofrequency catheter ablation of the slow pathway involved in atrioventricular nodal reentrant tachycardia. The patient subsequently returned 4 weeks later with acute radiation dermatitis that was retrospectively attributed to a malfunction in the fluoroscopy unit that lacked a maximum current output cut-off switch. Using dose reconstruction studies and her estimated biological response, we determined that she received between 15 and 20 Gy (1 Gy = 100 rads) to the skin on her back during the procedure. The exposure will result in an increase in her lifelong risk of skin and lung cancer. This article underscores the potential for radiation-induced injury during lengthy therapeutic procedures using x-ray equipment.

High dose neostigmine treatment of malignant sinus tachycardia.

Sinus tachycardia caused by circulating catecholamines in the setting of congestive heart failure may impair systemic perfusion because of decreased diastolic filling time. We report the case of a patient with Wolff-Parkinson-White syndrome with angina and cardiogenic shock who improved dramatically following administration of neostigmine. Cardiac output, blood pressure, and stroke volume increased as heart rate was reduced. A previous attempt at heart rate control, in the same patient, using a low dose beta-antagonist, precipitated hemodynamic collapse. The remarkable recovery of our patient suggests that acetylcholinesterase inhibitors may warrant further investigation in patients with severe sinus tachycardia.

Provocation of hypotension and pain during upright tilt table testing in adults with fibromyalgia.

OBJECTIVE: Fibromyalgia is a common but poorly understood problem characterized by widespread pain and chronic fatigue. Because chronic fatigue has been associated with neurally mediated hypotension, we examined the prevalence of abnormal responses to upright tilt table testing in 20 patients with fibromyalgia and 20 healthy controls. METHODS: Each subject completed a symptom questionnaire and underwent a three stage upright tilt table test (stage 1:45 minutes at 70 degrees tilt; stage 2, 15 minutes at 70 degrees tilt with isoproterenol 1-2 micrograms/min; stage 3, 10 minutes at 70 degrees tilt with isoproterenol 3-4 micrograms/min). An abnormal response to upright tilt was defined by syncope or presyncope in association with a drop in systolic blood pressure of at least 25 mm Hg and no associated increase in heart rate. RESULTS: During stage 1 of upright tilt, 12 of 20 fibromyalgia patients (60%), but no controls had an abnormal drop in blood pressure (P < 0.001). Among those with fibromyalgia, all 18 who tolerated upright tilt for more than 10 minutes reported worsening or provocation of their typical widespread fibromyalgia pain during stage 1. In contrast, controls were asymptomatic (P < 0.001). CONCLUSION: These results identify a strong association between fibromyalgia and neurally mediated hypotension. Further studies will be needed to determine whether the autonomic response to upright stress plays a primary role in the pathophysiology of pain and other symptoms in fibromyalgia.