Wouter Wieling

Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome

Roy Freeman • Wouter Wieling • Felicia B. Axelrod • David G. Benditt • Eduardo Benarroch • Italo Biaggioni • William P. Cheshire • Thomas Chelimsky • Pietro Cortelli • Christopher H. Gibbons • David S. Goldstein • Roger Hainsworth • Max J. Hilz • Giris Jacob • Horacio Kaufmann • Jens Jordan • Lewis A. Lipsitz • Benjamin D. Levine • Phillip A. Low • Christopher Mathias • Satish R. Raj • David Robertson • Paola Sandroni • Irwin Schatz • Ron Schondorff • Julian M. Stewart • J. Gert van Dijk

Pathophysiological basis of orthostatic hypotension in autonomic failure

In patients with autonomic failure orthostatic hypotension results from an impaired capacity to increase vascular resistance during standing. This fundamental defect leads to increased downward pooling of venous blood and a consequent reduction in stroke volume and cardiac output that exaggerates the orthostatic fall in blood pressure. The location of excessive venous blood pooling has not been established so far, but present data suggest that the abdominal compartment and perhaps leg skin vasculature are the most likely candidates. To improve the orthostatic tolerance in patients with autonomic failure, protective measures that reduce excessive orthostatic blood pooling have been developed and evaluated. These measures include physical counter‐manoeuvres and abdominal compression.

Feasibility of ambulatory, continuous 24-hour finger arterial pressure recording.

We tested Portapres, an innovative portable, battery-operated device for the continuous, noninvasive, 24-hour ambulatory measurement of blood pressure in the finger. Portapres is based on Finapres, a stationary device for the measurement of finger arterial pressure. Systems were added to record signals on tape, to alternate measurements between fingers automatically each 30 minutes, and to correct for the hydrostatic height of the hand. We compared the pressure as measured by Portapres with contralateral intrabrachial pressure measured with an Oxford device. Results were obtained in eight volunteers and 16 hypertensive patients. Time lost due to artifact was about 10% for each device. In two patients a full 24-hour Oxford profile was not obtained. In the remaining 22 subjects finger systolic, diastolic, and mean pressures differed +1 (SD 9), -8 (6), and -10 (6) mm Hg, respectively, from intrabrachial pressure. These diastolic and mean pressure underestimations are similar to what was found earlier for Finapres, are typical for the technique, and are systematic. Avoiding brisk hand movements resulted in fewer waveform artifacts. The hand had to be kept covered to continue recording at low outside temperatures. Sleep was not disturbed by Portapres, and arterial pressure showed a marked fall during siesta and nighttime. There were no major limitations in behavior, and no discomfort that originated from continuous monitoring was reported. Measurements continued normally during physical exercise. Portapres provides for the first time continuous 24-hour, noninvasive ambulatory blood pressure waveform monitoring and offers real and obvious advantages over current noninvasive and invasive devices.

Initial orthostatic hypotension: review of a forgotten condition

Several studies have shown that standing up is a frequent (3-10%) trigger of loss of consciousness both in young and old subjects. An exaggerated transient BP (blood pressure) fall upon standing is the underlying cause. IOH (initial orthostatic hypotension) is defined as a transient BP decrease within 15 s after standing, >40 mmHg SBP (systolic BP) and/or >20 mmHg DBP (diastolic BP) with symptoms of cerebral hypoperfusion. It differs distinctly from typical orthostatic hypotension (i.e. BP decrease >20 mmHg SBP and/or >10 mmHg DBP after 3 min of standing) as the BP decrease is transient. Only continuous beat-to-beat BP measurement during an active standing-up manoeuvre can document this condition. As IOH is only associated with active rising, passive tilting is of no diagnostic value. The pathophysiology of IOH is thought to be a temporal mismatch between cardiac output and vascular resistance. The marked decrease of vascular resistance during rising is similar to that observed at the onset of leg exercise and is absent during head-up tilting. It is attributed to vasodilatation in the working muscle through local mechanisms. Standing up causes an initial increase in venous return through the effects of contraction of leg and abdominal muscles. The consequent sudden increase in right atrial pressure may contribute to the fall in systemic vascular resistance through a reflex effect. This review alerts clinicians and clinician scientists to a common, yet often neglected, condition that occurs only upon an active change of posture and discusses its epidemiology, pathophysiology and management.

Lifetime cumulative incidence of syncope in the general population: a study of 549 Dutch subjects aged 35-60 years.

Introduction: There are limited and conflicting data on the lifetime cumulative incidence of syncope in the general population. The aim of our study was to determine the lifetime cumulative incidence and triggers of syncope in the general population.

Reflex control of heart rate in normal subjects in relation to age: A data base for cardiac vagal neuropathy

SummaryWe examined the heart rate changes induced by forced breathing and by standing up in 133 healthy subjects in the age range 10–65 years in order to establish a data base for studies on parasympathetic heart rate control in autonomic neuropathy. Test results declined with age. Log-transformation was used to define the lower limit of normal (P0.10) and an uncertainty range (values between P0.10 and P0.025). The lower limit of normal decreased from 22 to 11 beats/ min for forced breathing and from 26 to 16 beats/min for standing up, with age increasing from 10 to 65 years. No subject scored below and only two subjects scored in or below the uncertainty range for both tests. Lack of correlation between both tests (r=0.17) documents the different afferent mechanisms of the reflex heart rate changes. In combination these two tests form a simple and reliable bedside method to establish cardiac vagal neuropathy.

Pacemaker Therapy in Patients With Neurally Mediated Syncope and Documented Asystole Third International Study on Syncope of Uncertain Etiology (ISSUE-3): A Randomized Trial

Background— The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. Methods and Results— Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12±10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40–74) with pacemaker OFF and 25% (95% CI, 13–45) with pacemaker ON (log rank: P=0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4–81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient. Conclusions— Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00359203.Background— The efficacy of cardiac pacing for prevention of syncopal recurrences in patients with neurally mediated syncope is controversial. We wanted to determine whether pacing therapy reduces syncopal recurrences in patients with severe asystolic neurally mediated syncope. Methods and Results— Double-blind, randomized placebo-controlled study conducted in 29 centers in the Third International Study on Syncope of Uncertain Etiology (ISSUE-3) trial. Patients were ≥40 years, had experienced ≥3 syncopal episodes in the previous 2 years. Initially, 511 patients, received an implantable loop recorder; 89 of these had documentation of syncope with ≥3 s asystole or ≥6 s asystole without syncope within 12±10 months and met criteria for pacemaker implantation; 77 of 89 patients were randomly assigned to dual-chamber pacing with rate drop response or to sensing only. The data were analyzed on intention-to-treat principle. There was syncope recurrence during follow-up in 27 patients, 19 of whom had been assigned to pacemaker OFF and 8 to pacemaker ON. The 2-year estimated syncope recurrence rate was 57% (95% CI, 40–74) with pacemaker OFF and 25% (95% CI, 13–45) with pacemaker ON (log rank: P =0.039 at the threshold of statistical significance of 0.04). The risk of recurrence was reduced by 57% (95% CI, 4–81). Five patients had procedural complications: lead dislodgment in 4 requiring correction and subclavian vein thrombosis in 1 patient. Conclusions— Dual-chamber permanent pacing is effective in reducing recurrence of syncope in patients ≥40 years with severe asystolic neurally mediated syncope. The observed 32% absolute and 57% relative reduction in syncope recurrence support this invasive treatment for the relatively benign neurally mediated syncope. Clinical Trial Registration— URL: . Unique identifier: [NCT00359203][1]. # Clinical Perspective {#article-title-19} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00359203&atom=%2Fcirculationaha%2F125%2F21%2F2566.atom

Epidemiology of reflex syncope

Abstract.Cost-effective diagnostic approaches to reflex syncope require knowledge of its frequency and causes in different age groups. For this purpose we reviewed the available literature dealing with the epidemiology of reflex syncope.The incidence pattern of reflex syncope in the general population and general practice is bimodal with peaks in teenagers and in the elderly. In the young almost all cases of transient loss of consciousness are due to reflex syncope. The life-time cumulative incidence in young females (≅ 50 %) is about twice as high as in males (≅ 25 %). In the elderly, cardiac causes, orthostatic and postprandial hypotension, and the effects of medications are common, whereas typical vasovagal syncope is less frequent. In emergency departments, cardiac causes and orthostatic hypotension are more frequent especially in elderly subjects. Reflex syncope, however, remains the most common cause of syncope, but all-cause mortality in subjects with reflex syncope is not higher than in the general population. This knowledge about the epidemiology of reflex syncope can serve as a benchmark to develop cost-effective diagnostic approaches.

Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome.

Roy Freeman • Wouter Wieling • Felicia B. Axelrod • David G. Benditt • Eduardo Benarroch • Italo Biaggioni • William P. Cheshire • Thomas Chelimsky • Pietro Cortelli • Christopher H. Gibbons • David S. Goldstein • Roger Hainsworth • Max J. Hilz • Giris Jacob • Horacio Kaufmann • Jens Jordan • Lewis A. Lipsitz • Benjamin D. Levine • Phillip A. Low • Christopher Mathias • Satish R. Raj • David Robertson • Paola Sandroni • Irwin Schatz • Ron Schondorff • Julian M. Stewart • J. Gert van Dijk

Continuous finger arterial pressure: Utility in the cardiovascular laboratory

The clinical utility for autonomic research purposes of the FinapresTM, a device for measuring finger arterial pressure continuously and noninvasively, was assessed by estimating its accuracy, precision and within-subject variability in 48 subjects, aged 18–65 years, in comparison with intraarterial brachial blood pressure.At differences of −3.5 ± 12, −8.0 ± 8 and −4.4 ± 8 mmHg from simultaneous intrabrachial systolic, mean and diastolic pressure, the Finapres meets the Association for the Advan cement of Medical Instruments (AAMI) accuracy requirements for systolic and diastolic, but not for mean pressure. The precision requirements were nearly met for mean and diastolic, but not for systolic pressure. These results compare to those of others under widely varying circumstances in anaesthetized and awake subjects, and are comparable to those published for the auscultatory technique.The within-subject precision of Finapres is high; the 95% confidence intervals are 3.4–4.5 mmHg for systolic, 1.5–2.0 mmHg for mean and 1.7–2.2 mmHg for diastolic. This makes the Finapres suitable for tracking changes in blood pressure. Four case studies are provided as examples of the value of the Finapres in the clinical laboratory.