Left ventricular diastolic dysfunction in congenital chronic anaemias during childhood as determined by comprehensive echocardiographic imaging including acoustic quantification.

AIMS: To evaluate prospectively the left ventricular performance in thalassaemia major and sickle cell disease using comprehensive echocardiographic imaging including acoustic quantification during early childhood. METHODS AND RESULTS: Twenty-three patients with thalassaemia and 26 patients with sickle cell disease underwent echocardiographic examination including M-mode, 2-D, Doppler and acoustic quantification. All patients were matched for age, sex, weight and height with 20 normal controls. All patients were below 13 years of age. Thalassaemia and sickle cell disease patients were significantly anaemic when compared with normals (P<0.0001). All patients had normal left ventricular systolic parameters. Acoustic quantification-derived left ventricular volumes, filling rates, and emptying rates were not different in thalassaemia patients from controls. Left ventricular volumes, however, were larger in sickle cell disease patients than in controls. In contrast, by Doppler technique, left ventricular filling occurs mainly in early diastole (E wave) in thalassaemia patients and mainly in late diastole (A wave) in sickle cell disease patients, (P=0.03 and 0.01 respectively). E/A ratio was lower and diastolic filling period was shorter than normal in sickle cell disease but not in thalassaemia patients. Patients in both groups had left ventricular mass (determined by M-mode) significantly higher than normal (P<0.0001). CONCLUSION: The left ventricular systolic performance is well preserved in patients with chronic anaemia due to thalassaemia major and sickle cell disease during early childhood. In both diseases, however, there is left ventricular hypertrophy and measurable abnormalities in the diastolic filling detected by Doppler. Such changes do not fit a specific cardiomyopathic pattern due to diastolic dysfunction i.e. restrictive physiology vs delayed relaxation. Acoustic quantification of left ventricular diastolic parameters (filling rates) was less sensitive than Doppler in detecting these early diastolic abnormalities in both diseases.

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.

The relationship between neurally mediated hypotension and the chronic fatigue syndrome.

OBJECTIVE: To compare the clinical symptoms and response evoked by upright tilt-table testing in healthy individuals and in a sample of those satisfying strict criteria for chronic fatigue syndrome. DESIGN: Case-comparison study with mean (SD) follow-up of 24 (5) weeks. SETTING: Tertiary care hospital. PATIENTS AND OTHER PARTICIPANTS: A sample of 23 patients with chronic fatigue syndrome (five men and 18 women; mean age, 34 years), each of whom fulfilled the strict diagnostic criteria of the Centers for Disease Control and Prevention, was recruited from regional chronic fatigue support groups and from the investigators' clinical practices. There were 14 healthy controls (four men and 10 women; mean age, 36 years). INTERVENTIONS: 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 1 to 2 micrograms/min of isoproterenol; and stage 3, 10 minutes at 70 degrees with 3 to 4 micrograms/min of isoproterenol). Patients were offered therapy with fludrocortisone, beta-adrenergic blocking agents, and disopyramide, alone or in combination, directed at neurally mediated hypotension. MAIN OUTCOME MEASURES: Response to upright tilt and scores on symptom questionnaires prior to and during follow-up. RESULTS: An abnormal response to upright tilt was observed in 22 of 23 patients with chronic fatigue syndrome vs four of 14 controls (P < .001). Seventy percent of chronic fatigue syndrome patients, but no controls, had an abnormal response during stage 1 (P < .001). Nine patients reported complete or nearly complete resolution of chronic fatigue syndrome symptoms after therapy directed at neurally mediated hypotension. CONCLUSIONS: We conclude that chronic fatigue syndrome is associated with neurally mediated hypotension and that its symptoms may be improved in a subset of patients by therapy directed at this abnormal cardiovascular reflex.

Is neurally mediated hypotension an unrecognised cause of chronic fatigue?

Neurally mediated hypotension is now recognised as a common cause of otherwise unexplained recurrent syncope, but has not been reported in association with chronic fatigue. We describe seven consecutive non-syncopal adolescents with chronic post-exertional fatigue, four of whom satisfied strict criteria for chronic fatigue syndrome. Upright tilt-table testing induced significant hypotension in all seven (median systolic blood pressure 65 mm Hg, range 37-75), consistent with the physiology of neurally mediated hypotension. Four had prompt improvement in their chronic fatigue when treated with atenolol or disopyramide. These observations suggest an overlap in the symptoms of chronic fatigue syndrome and neurally mediated hypotension.