Lessons learned from the pilot study of an orthostatic hypotension intervention in the subacute phase following spinal cord injury.

Context: Following spinal cord injury (SCI) at the cervical or upper-thoracic level, orthostatic hypotension (OH) is observed in 13-100% of patients. This study aimed to test the feasibility of conducting a randomized controlled trial combining a dynamic tilt-table (Erigo®) and functional electrical stimulation (FES) to mitigate OH symptoms in the subacute phase after SCI. Design: Pilot study. Setting: A tertiary rehabilitation hospital. Participants: Inpatients who had a C4-T6 SCI (AIS A-D) less than 12 weeks before recruitment, and reported symptoms of OH in their medical chart. Interventions: Screening sit-up test to determine eligibility, then 1 assessment session and 3 intervention sessions with Erigo® and FES for eligible participants. Outcome measures: Recruitment rate, duration of assessment and interventions, resources used, blood pressure, and Calgary Presyncope Form (OH symptoms). Results: Amongst the 232 admissions, 148 inpatient charts were reviewed, 11 inpatients met all inclusion criteria, 7 participated in a screening sit-up test, and 2 exhibited OH. Neither of the two participants recruited in the pilot study was able to fully complete the assessment and intervention sessions due to scheduling issues (i.e. limited available time). Conclusion: This pilot study evidenced the non-feasibility of the clinical trial as originally designed, due to the low recruitment rate and the lack of available time for research in participant's weekday schedule. OH in the subacute phase after SCI was less prevalent and less incapacitating than expected. Conventional management and spontaneous resolution of symptoms appeared sufficient to mitigate OH in most patients with subacute SCI.

Usefulness of Tilt Testing and Carotid Sinus Massage for Evaluating Reflex Syncope.

Thirty years ago Tilt Testing (TT) was described as a tool in the diagnostic work-up of vasovagal syncope; after its initial success, some flaws have become evident. The concept of hypotensive susceptibility has provided the test a new relevance, shifting from diagnosis only, to therapeutic management. Carotid Sinus Massage (CSM) was introduced at the beginning of the XX century; the technique has evolved over years, whereas the concept of carotid sinus syndrome (CSS) has remained unchanged and uncontested for more than half a century. Nowadays, CSS is a matter of debate, with new classifications and criteria coming on the scene. Recently, a common central etiological mechanism has been hypothesized for reflex syncope, manifesting as CSS, vasovagal syncope or both. In this context, TT and CSM acquire an important role in clinical practice, being essential for a complete diagnosis and treatment. Recalling their historical background, the present paper illustrates an actual interpretation of TT and CSM.

Taquicardia ventricular polimórfica durante teste de inclinação na doença de Chagas / Polymorphic ventricular tachycardia during tilt testing in Chagas disease

Paciente do sexo masculino, de 62 anos de idade, com megacólon chagásico sem manifestações cardíacas, apresentou evento sincopal sem pródromos, sendo submetido a Holter de 24 horas, ecocardiografia, teste ergométrico e cineangiocoronariografia, que se mostraram normais. O estudo eletrofisiológico mostrou ausência de distúrbios de condução e de indução de taquiarritmias. Durante a fase basal do teste de inclinação, o paciente apresentou taquicardia ventricular polimórfica. Foi realizado implante de cardioversor-desfibrilador implantável. Na evolução, apresentou deterioração da função ventricular com início de terapêutica específica. Após sete anos de acompanhamento, observaram-se três episódios de taquicardia ventricular polimórfica adequadamente revertidos pelo cardioversor-desfibrilador implantável

A 62 year-old man with Chagasic megacolon without cardiac manifestations developed a syncope without prodrome and was submitted to 24-hour Holter monitoring, echocardiogram, exercise test and coronary angiography. Electrophysiology tests showed there was no conduction and tachyarrhythmia induction disorders. During the baseline phase of the tilt test, the patient presented a polymorphic ventricular tachycardia. An implantable cardioverter defibrillator was implanted. At the follow-up, the patient presented left ventricular deterioration and specific therapy was started. After seven years of follow-up, three episodes of polymorphic ventricular tachycardia were observed and were successfully converted

Use of an allostatic neurotechnology by adolescents with postural orthostatic tachycardia syndrome (POTS) is associated with improvements in heart rate variability and changes in temporal lobe electrical activity.

Autonomic dysregulation and heterogeneous symptoms characterize postural orthostatic tachycardia syndrome (POTS). This study evaluated the effect of high-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM(®)), a noninvasive, allostatic neurotechnology for relaxation and auto-calibration of neural oscillations, on heart rate variability, brain asymmetry, and autonomic symptoms, in adolescents with POTS. Seven subjects with POTS (three males, ages 15-18) underwent a median of 14 (10-16) HIRREM sessions over 13 (8-17) days. Autonomic function was assessed from 10-min continuous heart rate and blood pressure recordings, pre- and post-HIRREM. One-minute epochs of temporal high-frequency (23-36 Hz) brain electrical activity data (T3 and T4, eyes closed) were analyzed from baseline HIRREM assessment and subsequent sessions. Subjects rated autonomic symptoms before and after HIRREM. Four of seven were on fludrocortisone, which was stopped before or during their sessions. Heart rate variability in the time domain (standard deviation of the beat-to-beat interval) increased post-HIRREM (mean increase 51%, range 10-143, p = 0.03), as did baroreflex sensitivity (mean increase in high-frequency alpha 65%, range -6 to 180, p = 0.05). Baseline temporal electrical asymmetry negatively correlated with change in asymmetry from assessment to the final HIRREM session (p = 0.01). Summed high-frequency amplitudes at left and right temporal lobes decreased a median of 3.8 µV (p = 0.02). There was a trend for improvements in self-reported symptoms related to the autonomic nervous system. Use of HIRREM was associated with reduced sympathetic bias in autonomic cardiovascular regulation, greater symmetry and reduced amplitudes in temporal lobe high-frequency electrical activity, and a trend for reduced autonomic symptoms. Data suggest the potential for allostatic neurotechnology to facilitate increased flexibility in autonomic cardiovascular regulation, possibly through more balanced activity at regions of the neocortex responsible for autonomic management. Clinical trial registry "Tilt Table with Suspected postural orthostatic tachycardia syndrome (POTS) Subjects," Protocol Record: WFUBAHA01.

Noninvasive characterization of atrioventricular conduction in patients with atrial fibrillation.

The atrioventricular (AV) node plays a fundamental role in patients with atrial fibrillation (AF), acting as a filter to the numerous irregular atrial impulses which bombard the node. A phenomenological approach to better understand AV nodal electrophysiology is to analyze the ventricular response with respect to irregularity. In different cohorts of AF patients, such analysis has been performed with the aim to evaluate the association between ventricular response characteristics and long-term clinical outcome and to determine whether irregularity is affected by rate-control drugs. Another approach to studying AV nodal characteristics is to employ a mathematical model which accounts for the refractory periods of the two AV nodal pathways. With atrial fibrillatory rate and RR intervals as input, the model has been considered for analyzing data during (i) rest and head-up tilt test, (ii) tecadenoson and esmolol, and (iii) rate-control drugs. The present paper provides an overview of our recent work on the characterization and assessment of AV nodal conduction using these two approaches.

A non-human primate model for investigating drug-induced risk of orthostatic hypotension and sympathetic dysfunction: Preclinical correlate to a clinical test.

INTRODUCTION: Drug induced orthostatic hypotension (OH) is an important clinical concern and can be an unexpected hurdle during drug development. OH is defined as an abnormal decrease in blood pressure (BP) triggered by a rapid postural change. The sympathetic nervous system is critical for controlling normal cardiovascular function and compensatory responses to changes in posture. Thus, OH can also serve as a surrogate indicator of sympathetic dysfunction. However, preclinical conscious models for investigating risk of OH and/or sympathetic dysfunction are lacking. Herein, we describe a conscious nonhuman primate (NHP) model which mimics the widely used clinical tilt table test for OH. METHODS: Male, Cynomolgus NHPs (n = 7-8) implanted with radio-telemetry transmitters were placed in modified tilt chairs in a supine position. Subsequently, a 90° head up tilt was performed for 3 min followed by return to the supine position. BP and heart rate were continuously monitored. Test compounds were administered either intravenously or via oral gavage in a crossover design, with blood samples collected at the end of the each tilt to assess total drug concentrations. RESULTS: Tilt responses were assessed following treatment with positive control compounds that cause sympathetic dysfunction; hexamethonium (ganglionic blocker) and prazosin (alpha-1 adrenergic receptor antagonist). Both compounds induced marked OH as evidenced by robust and sustained BP reduction in response to a head up tilt (decrease of 25-35 mmHg for hexamethonium, decrease of 21-44 mmHg for prazosin). OH incidence rates increased in a dose-dependent manner. OH incidences following treatment with minoxidil (vasodilator) were markedly lower to those observed with hexamethonium and prazosin indicating the role of sympathetic dysfunction in causing OH. DISCUSSION: These data demonstrate that the NHP tilt test is a valuable model for investigating OH risk. This model fills an important preclinical gap for assessing such a safety concern and can be applied to programs where a sympathetic deficit and/or OH are anticipated or clinically observed.

[Syncope-- reasonable diagnostic tools to identify potentially dangerous syncopes]. / Synkopen - sinnvolle Diagnostik zur Identifizierung maligner Synkopen.

Syncopes are quite often seen by family doctors and in emergency wards. It is of utmost importance to differentiate between syncope of cardiac and non-cardiac origin, as prognosis and work-up are very different. Regularly used diagnostic tools, their indication and yield and finally an algorithm for a work-up are outlined.

Determinants of a positive response to carotid sinus massage and head-up tilt testing.

BACKGROUND: Orthostatic hypotension (OH) and carotid sinus hypersensitivity (CSH) are common causes of syncope in older people. The aim of this study was to determine if patient's age, sex and presenting symptoms influence the result of carotid sinus massage and head-up tilt testing. METHODS: Retrospective analysis of the database and reports was carried out between 1995 and 2006 at a tertiary referral centre. Patient's age, sex, presenting symptoms and test result were examined. Presenting symptoms were classified as syncope, falls or dizzy spells. RESULTS: Of the 1583 tests reported, OH was present in 402 patients (25.4%), of whom 175 (11.1%) were symptomatic. 188 of 1464 (12.8%) patients undergoing carotid sinus massage had evidence of CSH, of which 156 were symptomatic. Male patients were significantly more likely to have symptomatic CSH than female patients (odds ratio 2.28, 95% CI 1.54 to 3.04, p<0.01). There were non-significant trends to increased diagnosis of symptomatic OH with increasing age, male sex and referral with syncope. There were non-significant trends to increased diagnosis of symptomatic CSH with increasing age and referral with syncope. CONCLUSION: Male sex, increasing age and being referred with syncope were all associated with an increased likelihood of receiving a diagnosis of either OH or CSH. The overall prevalence of CSH was lower than in previous studies, which may reflect different patient populations.

The role of tilt training in preventing recurrent syncope in patients with vasovagal syncope: a prospective and randomized study.

BACKGROUND: Recurrent vasovagal syncope (VVS) can be a severely disabling disorder that may lead to an important deterioration of quality of life because of the severity and recurrence of episodes. This study sought to investigate the effectiveness of repeated orthostatic self-training in preventing syncope in patients with recurrent VVS. METHODS: Eighty-two consecutive patients (mean age 41 +/- 4 years, 37 males) with recurrent VVS episodes and positive head-up tilt testing (HUT) were enrolled in this study. The patients were then randomized (1:1) to conventional therapy or conventional therapy plus additional tilt training sessions. The patients were followed for spontaneous syncope for one year. Primary end-points were the recurrence of syncope, the number of episodes, and the interval of time to the first recurrence. RESULTS: There were no significant differences of baseline clinical characteristics and parameters of HUT between the tilt training and control groups. The patients had 4 +/- 2/year syncopal episodes prior to the HUT. The mean follow-up after randomization was 12 +/- 2 months. Spontaneous syncope recurrence during follow-up was 56% (23 patients) versus 37% (15 patients) in the control and tilt training groups, respectively (P = 0.1). Time to first recurrence was also similar in both groups (70 +/- 20 days vs 50 +/- 15 days, P = 0.09). The frequency of recurrent syncopes was similar in all types of VVSs while the rate of episodes was significantly higher in control group in patients with vasodepressor type during follow-up period (32% vs 10%, P = 0.04). The mean number of recurrent syncope episodes was also similar in both groups (3 +/- 1 vs 2 +/- 1, P = 0.4). CONCLUSIONS: Tilt training was unable to influence the spontaneous syncope recurrence for recurrent VVS except for vasodepressor type.

Neurally mediated syncope in children: results of tilt testing, treatment, and long-term follow-up.

Despite a great deal of literature concerning children with neurally mediated syncope (NMS) there is no clear standard of diagnosis or consistent approach to therapy. This report reviews our experience with tilt testing all patients who presented with syncope during a 3-year period. All patients referred for evaluation of syncope who underwent tilt testing were retrospectively reviewed. Follow-up was obtained at return visits or by telephone interview. Sixty patients were identified. The average age was 13.5 +/- 3.0 years. Twenty-six patients (43%) had positive tilt tests. Follow-up was available for 56 patients. Twelve of these patients had causes other than NMS found for their symptoms. The remaining 44 patients all had histories consistent with NMS. Nineteen of these patients had positive tilt tests. All 44 patients reported either a decrease or no recurrence of syncope, and 41 patients reported a decrease or no recurrence of presyncopal symptoms. Recurrence of syncope or symptoms was not related to the results of the tilt test. Twenty-five of the 44 patients used conservative measures (extra fluids or supplemental salt) and only 3 patients were taking medications. The use of conservative measures or medications was not related to the tilt test results. Tilt testing has a high false-negative and false-positive rate and should not be used as the standard for identifying patients with NMS. The long-term follow-up of patients with NMS demonstrates that regardless of the results of the tilt test, almost all have improved or resolved symptoms with simple interventions.