Salt supplementation in the management of orthostatic intolerance: Vasovagal syncope and postural orthostatic tachycardia syndrome.

Salt supplementation is a common non-pharmacological approach to the management of recurrent orthostatic syncope or presyncope, particularly for patients with vasovagal syncope (VVS) or postural orthostatic tachycardia syndrome (POTS), although there is limited consensus on the optimal dosage, formulation and duration of treatment. Accordingly, we reviewed the evidence for the use of salt supplementation to reduce susceptibility to syncope or presyncope in patients with VVS and POTS. We found that short-term (~3 months) salt supplementation improves susceptibility to VVS and associated symptoms, with little effect on supine blood pressure. In patients with VVS, salt supplementation is associated with increases in plasma volume, and an increase in the time taken to provoke a syncopal event during orthostatic tolerance testing, with smaller orthostatic heart rate increases, enhanced peripheral vascular responses to orthostatic stress, and improved cerebral autoregulation. Responses were most pronounced in those with a baseline sodium excretion <170 mmol/day. Salt supplementation also improved symptoms, plasma volume, and orthostatic responses in patients with POTS. Salt supplementation should be considered for individuals with recurrent and troublesome episodes of VVS or POTS without cardiovascular comorbidities, particularly if their typical urinary sodium excretion is low, and their supine blood pressure is not elevated. The efficacy of the response, in terms of the improvement in subjective and objective markers of orthostatic intolerance, and any potential deleterious effect on supine blood pressure, should be routinely monitored in individuals on high salt regimes.

The face of postural tachycardia syndrome - insights from a large cross-sectional online community-based survey.

BACKGROUND: Patients with postural tachycardia syndrome (POTS) experience chronic symptoms of orthostatic intolerance. There are minimal data detailing the demographics, clinical features and clinical course of this condition. This online, community-based survey highlights patients' experience with POTS. It consists of the largest sample of POTS patients reported to date. OBJECTIVES: To describe the demographics, past medical history, medications, treatments and diagnostic journey for patients living with POTS. METHODS: Postural tachycardia syndrome patients completed an online, community-based, cross-sectional survey. Participants were excluded if they had not received a diagnosis of POTS from a physician. The questions focused on the patient experience and journey, rather than physiological responses. RESULTS: The final analysis included 4835 participants. POTS predominantly affects white (93%) females (94%) of childbearing age, with approximately half developing symptoms in adolescence (mode 14 years). POTS is a chronic multisystem disorder involving a broad array of symptoms, with many patients diagnosed with comorbidities in addition to POTS. POTS patients often experience lengthy delays [median (interquartile range) 24 (6-72) months] and misdiagnosis, but the diagnostic delay is improving. POTS patients can present with a myriad of symptoms most commonly including lightheadedness (99%), tachycardia (97%), presyncope (94%), headache (94%) and difficulty concentrating (94%). CONCLUSIONS: These data provide important insights into the background, clinical features and diagnostic journey of patients suffering from POTS. These data should serve as an essential step for moving forward with future studies aimed at early and accurate diagnoses of these patients leading to appropriate treatments for their symptoms.

Production of Pectinase from Bacillus sonorensis MPTD1.

Seven isolates from spoiled fruits and vegetables were screened for pectinase production using pectin agar plates and the most efficient bacterial strain, MPTD1, was identified as Bacillus sonorensis. Optimisation of various process parameters was done using Plackett-Burman and Box-Behnken designs and it was found that parameters like yeast extract, K2HPO4, incubation time, NaNO3 and KCl have a negative impact on pectinase production. Parameters like pH and MgSO4 and pectin mass fractions have a positive impact on pectinase production. The maximum obtained enzyme activity was 2.43 (µM/mL)/min. This is the first report on pectinase production by Bacillus sonorensis.

A cross-sectional study contrasting olfactory function in autonomic disorders.

OBJECTIVE: To compare odor identification function in patients with peripheral or central autonomic neurodegeneration and in patients with intact autonomic neurons but undetectable norepinephrine. METHODS: Olfactory function was evaluated with the University of Pennsylvania Smell Identification Test (UPSIT) in 12 patients with pure autonomic failure, 10 patients with multiple system atrophy, and 4 patients with dopamine ß-hydroxylase deficiency. Blood pressure and catecholamine data were also compared. RESULTS: Odor identification was significantly impaired in patients with pure autonomic failure relative to patients with multiple system atrophy or dopamine ß-hydroxylase deficiency. Out of 40 odors, the patients correctly identified mean (95% confidence interval) 19.2 (14.1 to 24.2), 34.4 (32.2 to 36.6), and 31.7 (29.4 to 34.1) (p < 0.001). The difference between patients with pure autonomic failure and those with multiple system atrophy or dopamine ß-hydroxylase deficiency persisted after adjustment for age (p = 0.001). Patients with pure autonomic failure also had a greater orthostatic fall in blood pressure and lower plasma norepinephrine levels than patients with multiple system atrophy. CONCLUSIONS: Olfactory function was relatively intact in patients with dopamine ß-hydroxylase deficiency, who have intact noradrenergic neurons but lack norepinephrine. Odor identification was impaired in pure autonomic failure but not in multiple system atrophy, suggesting that 1) peripheral noradrenergic innervation is important for olfactory identification but norepinephrine is not essential and 2) UPSIT may be useful in the differential diagnosis between these disorders.

Psychiatric profile and attention deficits in postural tachycardia syndrome.

OBJECTIVES: Patients with postural tachycardia syndrome (POTS) often appear anxious and report inattention. Patients with POTS were formally assessed for psychiatric disorders and inattention and compared with patients with attention deficit hyperactivity disorder (ADHD) and control subjects. METHODS: Patients with POTS (n = 21), ADHD (n = 18) and normal control subjects (n = 20) were assessed for DSM-IV psychiatric disorders and completed a battery of questionnaires that assessed depression, anxiety and ADHD characteristics. RESULTS: Patients with POTS did not have an increased prevalence of major depression or anxiety disorders, including panic disorder, compared with the general population. Patients with POTS had mild depression. They scored as moderately anxious on the Beck Anxiety Inventory but did not exhibit a high level of anxiety sensitivity. Patients with POTS scored significantly higher on inattention and ADHD subscales than control subjects. These symptoms were not present during childhood. CONCLUSIONS: Patients with POTS do not have an increased lifetime prevalence of psychiatric disorders. Although they may seem anxious, they do not have excess cognitive anxiety. They do experience significant inattention which may be an important source of disability.

The hemodynamic and neurohumoral phenotype of postural tachycardia syndrome.

BACKGROUND: Previous studies of patients with postural tachycardia syndrome (POTS) have been hampered by relatively small cohorts, failure to control medications and diet, and inconsistent testing procedures. METHODS: The Vanderbilt Autonomic Dysfunction Center Database provided results of posture studies performed in 165 patients and 66 normal controls after dietary and medication restrictions. All posture studies were performed after an overnight fast and > or =30 minutes of supine rest. RESULTS: In both the supine and standing positions, heart rate (HR) and plasma concentrations of norepinephrine (NE), epinephrine, and dopamine were higher in patients with POTS compared with the healthy controls. Supine diastolic blood pressure (BP) was also elevated in POTS, whereas supine plasma l-3,4-dihydroxyphenyalanine was reduced. In an analysis of patient subgroups with either an upright plasma NE > or = 3.54 nM (high NE) or an upright plasma NE < 3.54 nM (normal NE), HR and BP were greater in the patient subgroup with high NE. In addition to these significant differences in hemodynamic and catechol measurements, we demonstrated that supine and standing plasma aldosterone and the aldosterone/renin ratio were decreased in patients with POTS. Plasma renin activity (PRA) tended to be higher in patients, and standing HR for those in the highest PRA quartile was significantly greater than for those in the lowest PRA quartile. CONCLUSIONS: Our results from larger cohorts of patients and controls than previously studied confirm published findings and contribute additional evidence of sympathetic activation in postural tachycardia syndrome (POTS). Abnormalities in the renin-angiotensin-aldosterone system may also contribute to the POTS phenotype.

The implantable cardioverter-defibrillator. Current indications and controversies.

The implantable cardioverter-defibrillator (ICD) has become a highly effective, but expensive therapy for sudden cardiac death due to ventricular tachyarrhythmias. ICD use has been increasing at 20-30% per year, and is expected to rise at a faster rate. Clinical trials have now shown that the ICD can be effective for the secondary prevention, and more recently for the primary prevention, of sudden cardiac death in selected populations. Despite the high quality trial evidence that is currently available, several issues pertaining to ICD use remain unresolved. These relate to the management of patient groups who were not included in the clinical trials, optimizing the selection of patients who will benefit from an ICD, determining the duration of survival benefit from an ICD, assessing and optimizing a patient's quality of life with an ICD, and determining the cost-effectiveness and cost-impact of the ICD. These considerations are discussed in this article.

Cyclooxygenase-2 blockade does not impair endothelial vasodilator function in healthy volunteers: randomized evaluation of rofecoxib versus naproxen on endothelium-dependent vasodilatation.

BACKGROUND: From a cardiovascular standpoint, the safety of cyclooxygenase-2 (COX-2) blockers has been a topic of increasing concern. This concern stemmed from observations indicating that the COX-2 isoform is the major source of endothelium-derived prostacyclin and, hence, that selective blockade of this enzyme may impair endothelial health. To investigate this matter, we examined the effects of 7 days of treatment with rofecoxib versus naproxen on endothelial function in healthy volunteers. METHODS AND RESULTS: Thirty-five healthy volunteers were randomized to receive 7-day treatment with either rofecoxib (25 mg/d, n=18) or naproxen (750 mg/d, n=17). Vascular response measurements were conducted using forearm strain-gauge plethysmography. Changes in forearm blood flow in response to the endothelium-dependent vasodilator acetylcholine (3, 10, and 30 microg/min) and the endothelium-independent vasodilator sodium nitroprusside (1 and 10 microg/min) were assessed before and after treatment. Acetylcholine evoked a dose-dependent increase in forearm blood flow in all groups. Importantly, treatment resulted in no change in acetylcholine-mediated increases in forearm blood flow in either group (naproxen, P=0.27; rofecoxib, P=0.58). Similarly, there was no change in forearm blood flow in response to sodium nitroprusside (naproxen, P=0.55; rofecoxib, P=0.63). CONCLUSIONS: We herein describe, for the first time, the effects of COX-2-selective inhibition on endothelium-dependent vasodilatation in healthy adults. COX-2 blockade, when used at the doses employed therapeutically (which are known to inhibit vascular prostacyclin production) did not result in significant changes in endothelial vasodilator responses in healthy volunteers. The effects of COX-2 inhibitors on vasodilator responses in patients with coronary artery disease remain to be determined.

The implantable cardioverter-defibrillator: does everybody need one?

The implantable cardioverter-defibrillator (ICD) has emerged as an effective, but expensive, therapy for arrhythmic sudden cardiac death. ICD use has been increasing by 20% to 30% per year. Clinical trials have shown that the ICD can be effective for both the primary prevention and the secondary prevention of sudden cardiac death in selected populations. Despite the available trial evidence, several issues pertaining to ICD use remain unresolved, including the treatment of patients not represented in clinical trials, the optimal selection of patients who will benefit from an ICD, the duration of benefit from an ICD, the quality of life for patients with an ICD, and both the cost-effectiveness and the cost impact of the ICD. These considerations are discussed in this article.

Dysautonomia among patients with fibromyalgia: a noninvasive assessment.

OBJECTIVE: Fibromyalgia (FM) is a prevalent and poorly understood disorder associated with a significant amount of disability. Some clinical characteristics are common to both FM and vasovagal syncope (which is caused by dysautonomia). We assessed the response of patients with FM to a head up tilt table test (HUT). We also examined sympathovagal balance by assessing heart rate variability (HRV). METHODS: We studied 17 women with FM and 14 female control subjects. After baseline functional assessments, they underwent a 3 stage HUT (with isoproterenol). HRV was assessed over a 24 h period and also before and during HUT. Quality of life was assessed using the Medical Outcomes Study SF-36 Short Form Health Survey. RESULTS: HUT was positive in 64.7% of the patients with FM compared with 21.3% of controls (p = 0.016). FM patients had less HRV, as measured by either time domain or frequency domain analysis. The FM group had a different response to HUT than controls. Quality of life was significantly lower in patients with FM compared to controls (p < or = 0.001 in all domains). CONCLUSION: Patients with FM have abnormal responses to 2 tests of autonomic nervous system function. Further research is needed to determine if dysautonomia plays a role in the pathogenesis of FM or is a result of FM.

Correlation of waiting time with adverse events in patients admitted for nonelective permanent pacemaker implantation.

OBJECTIVE: To determine the effect of a dedicated permanent pacemaker implantation procedure room on waiting time and waiting time-related morbidity. DESIGN: Retrospective chart review. SETTING: Two tertiary care teaching hospitals in southern Ontario; one with a dedicated procedure room (centre B) and one without (centre A). PATIENTS: Two hundred and fourteen consecutive patients who required permanent pacing urgently or emergently. METHODS: Charts were examined retrospectively at centre A (131 patients) and centre B (83 patients) to determine the waiting time for and the number of preoperative adverse events in nonelective permanent pacemaker implantation. RESULTS: Patients in centre A waited a mean of 4.5 +/- 3.0 days while patients in centre B waited a mean of 1.9 +/- 1.6 days (P = 0.0001). Centre A patients experienced a total of 57 adverse events that were likely or possibly related to the waiting period, while patients at centre B experienced eight such events (P < 0.0001). Thirty-three per cent of the centre A patients experienced at least one adverse event, while 8% of centre B patients experienced at least one adverse event (P < 0.00001). Of the centre A patients who waited for more than six days (26 patients), 58% had at least one adverse event, compared with 26% of those who waited less than six days (105 patients, P = 0.0009). CONCLUSIONS: Delays in implanting nonelective permanent pacemakers are strongly associated with an increase in adverse events. Measures to shorten the waiting time are likely to result in a reduction in morbidity in conjunction with a beneficial impact on health care resource utilization.

Is there a sex bias in the selection of permanent pacemaker implantations?

OBJECTIVE: To determine whether there is a sex bias in a historical cohort of consecutive patients who underwent initial pacemaker implantation at a Canadian teaching hospital by determining whether women were less likely to receive physiological pacemakers. DESIGN: Retrospective chart review. SETTING: A Canadian, tertiary care teaching hospital. PATIENTS: A total of 446 patients (192 female) had a first-time pacemaker implantation between January 1, 1990 and September 30, 1993 at Kingston General Hospital, Kingston, Ontario. RESULTS: Physiological pacemakers (dual chamber or atrial only) were implanted in 125 male patients (49.2%) and in 93 female patients (48.4%), for an absolute difference of 0.8%. In patients deemed eligible for physiological pacemaker implantation (absence of absolute or relative contraindications to physiological pacing), 63.8% of male patients and 60.6% of female patients received physiological pacemakers. Pacemakers with rate-modulation were implanted in 109 male patients (42.9%) and in 80 female patients (41.7%). These differences were not significant. CONCLUSION: No sex difference in the selection of physiological or rate-modulated permanent pacemakers was demonstrated in this study.