Intermittent Calf Compression Delays the Onset of Presyncope in Young Healthy Individuals

Abstract

Orthostatic fluid shifts reduce the effective circulating volume and thus contribute to syncope susceptibility. Recurrent syncope has a devastating impact on quality of life and is challenging to manage effectively. To blunt orthostatic fluid shifts, static calf compression garments are often prescribed to patients with syncope, but have questionable efficacy. Intermittent calf compression, which mimics the skeletal muscle pump to minimize pooling and filtration, holds promise for the management of syncope. We aimed to evaluate the effectiveness of intermittent calf compression for increasing orthostatic tolerance (OT; time to presyncope). We conducted a randomized single-blind crossover study, in which participants (n = 21) underwent three graded 60° head-up-tilt tests to presyncope with combined lower body negative pressure on separate days. Low frequency intermittent calf compression (ICLF; 4 s on and 11 s off) at 0-30 and 0-60 mmHg was applied during two tests and compared to a placebo condition where the garment was fitted, but no compression applied. We measured continuous leg circumference changes (strain gauge plethysmography), cardiovascular responses (finger plethysmography; Finometer Pro), end tidal gases (nasal cannula), and cerebral blood flow velocity (CBFv, transcranial Doppler). The 0-60 mmHg ICLF increased OT (33 ± 2.2 min) compared to both placebo (26 ± 2.4 min; p < 0.001) and 0-30 mmHg ICLF (25 ± 2.7 min; p < 0.001). Throughout testing 0-60 mmHg ICLF reduced orthostatic fluid shifts compared to both placebo and 0-30 mmHg ICLF (p < 0.001), with an associated improvement in stroke volume (p < 0.001), allowing blood pressure to be maintained at a reduced heart rate (p < 0.001). In addition, CBFv was higher with 0-60 mmHg ICLF than 0-30 mmHg ICLF and placebo (p < 0.001). Intermittent calf compression is a promising novel intervention for the management of orthostatic intolerance, which may provide affected individuals renewed independence and improved quality of life.

Keywords: cardiovascular; compression stockings; filtration; orthostasis; orthostatic tolerance; syncope; venous pooling.

FIGURE 1

Experimental protocol. On each test day participants provided written informed consent, were familiarized with the experimental procedures, and were instrumented with cardiovascular and plethysmographic monitoring. After 20 min of supine rest they underwent a 60° head-up tilt test to presyncope with combined, graded lower body negative pressure. After 20 min upright, lower body negative pressure was applied and incremented (–20, –40, –60 mmHg) at 10 min intervals. The test was terminated at presyncope, at participant request or upon completion of the entire protocol. Orthostatic tolerance was determined as the time from tilt start to test termination. On each of the three test days, a different compression paradigm was applied: 0–30 mmHg low frequency intermittent compression, 0–60 mmHg low frequency intermittent compression, or a placebo condition where the garment was fitted but no compression was applied. LBNP, lower body negative pressure.

FIGURE 2

Compression system. The compression system encompassed a pressure regulator, a pressure source, a valve control box and two compression cuffs (adult large), shown above from left to right. The pressure source was connected to a valve control box with an Arduino board and programmable Arduino chip, which allowed us to program the valve system to cycle from open for 4 s to closed for 11 s throughout the test. In addition, the pressure inside one of the compression cuffs was continuously monitored throughout testing with the use of a pressure transducer.

FIGURE 3

Orthostatic tolerance. (A) Orthostatic tolerance, rounded to the nearest minute, is shown for all three tilt conditions. (B) Kaplan–Meier plot depicting the proportion of participants remaining (who have not reached presyncope) in each condition at any given tilt time. (C) Bar plots showing the mean improvement in orthostatic tolerance for each compression condition relative to the placebo. (D) The mean improvement in orthostatic tolerance with 0–60 mmHg compression compared to placebo was dependent on baseline orthostatic tolerance (placebo). ^∗Significantly different from placebo (p < 0.05); †significantly different from 0 to 30 mmHg compression (p < 0.05). Shaded gray boxes of increasing intensity represent stages of the tilt test and increasing orthostatic stress. OT, orthostatic tolerance.

FIGURE 4

Venous pooling and capillary filtration during tilt testing. The time course of pooling and filtration in the calf (A) and at the level of the gaiter (B). Data are presented as a percentage change form supine and symbols (mean ± SEM) reflect mean data from the right and left calves/gaiters combined, from the final 30 s of every 2 min interval. Main effects of condition throughout tilt are shown. ^∗Significantly different from placebo (p < 0.001); ^†Significantly different from 0 to 30 mmHg compression. BL, baseline; HUT, head-upright tilt; LBNP, lower body negative pressure.

FIGURE 5

Blood pressure and heart rate responses during tilt testing. The time course of blood pressure (A) and heart rate (B) during tilt are shown. Symbols (mean ± SEM) reflect averaged data, over the last 30 s of every 2 min interval. Main effects of condition throughout tilt are shown. ^∗Significantly different from placebo (p < 0.001); ^†Significantly different from 0 to 30 mmHg compression. BP, blood pressure; SAP, systolic arterial pressure; DAP, diastolic arterial pressure; HR, heart rate; BL, baseline; HUT, head-upright tilt; LBNP, lower body negative pressure.

FIGURE 6

Stroke volume, cardiac output, cerebral blood flow velocity and end-tidal CO₂ responses during tilt testing. The time course of stroke volume (A), cardiac output (B), cerebral blood flow velocity (C) and end-tidal carbon dioxide (D) during tilt are shown. Symbols (mean ± SEM) reflect averaged data, over the last 30 s of every 2 min interval and are reported as a percentage change from supine values. Main effects of condition throughout tilt are shown. ^∗Significantly different from placebo (p < 0.001); ^†significantly different from 0 to 30 mmHg compression. SV, stroke volume; CO, cardiac output; CBFv, cerebral blood flow velocity; P_ETCO_2, end tidal partial pressure of carbon dioxide; BL, baseline; HUT, head-upright tilt; LBNP, lower body negative pressure.

FIGURE 7

Systolic arterial pressure (SAP) reduction in the initial 30 s of head-up tilt. For each participant, the area of the SAP curve that dipped below baseline values throughout the first 30 s of HUT was integrated for each condition. The area under the curve of the SAP dip for was summed for each participant in each condition. (A) A sample trace from one participant showing the SAP time course in the first 30 s of tilt in the three conditions. (B) The integrated area between the baseline and SAP curves in each of the three conditions for the same sample participant. (C) The cumulative summed area for all participants in each of the three compression conditions throughout the first 30 s of tilt. (D) Boxplots comparing the cumulative summed area between the baseline and SAP curves for each participant in the three conditions. Solid lines show the sample median, while dashed lines depict the sample mean.