Deconditioning, orthostatic intolerance, exercise and chronic illness: Part 3

POTS (postural orthostatic tachycardia syndrome) is one type of orthostatic intolerance. It is defined as the increase in heart rate of 30 beats/min or more when standing in the absence of orthostatic hypotension. There are a number of mechanisms that cause POTS.

Neuropathic POTS is caused by inefficient constriction of blood vessels in the lower limbs due to a defect in the sympathetic nervous system. In these patients , the heart does not sense the change in blood pressure correctly and does not pump out enough blood volume to accommodate the pressure change. Patients with this syndrome usually do not sweat in the feet. They have insufficient release of norepinephrine upon standing.

The orthostatic intolerance in neuropathic POTS is caused by the veins not constricting enough in the legs to maintain blood pressure upon standing. When executing the Valsalva maneuver, they are unable to raise blood pressure significantly. Blood is found to pool in the leg veins when these patients do not use pressure devices like compression stockings. These patients have “high blood flow”, meaning that the total peripheral resistance (the total pressure exerted by the blood vessels) is lower than expected when laying down or standing. This form of POTS may have an autoimmune link, but this though requires further investigation.

Hyperadrenergic POTS is caused by excessive cardiac response to stimulation by the sympathetic nervous system. In these patients, the nervous system tells the heart to beat faster and harder.  30-60% of patients have this form. These patients have serum plasma norepinephrine of 600 pg/mL or higher when standing. They have fluctuating or elevated blood pressure (both consistently or during crisis), and episodes of tachycardia, hypertension and hyperhidrosis. Of note, these episodes can be triggered by orthostatic stimuli (changing position) as well as physical or even emotional stimuli.

This category has also been referred to as “low volume” POTS, in which norepinephrine levels in serum can exceed 1000 pg/mL, and in which patients often have pale and cold skin, tachycardia while laying down, elevated blood pressure while laying down and increased neurologic signals to muscles while laying down. A genetic condition affecting the norepinephrine transporter (NET) gene is responsible for some cases of hyperadrenergic POTS. Hyperadrenergic POTS can be secondary to a number of conditions, including mast cell activation disease. One study found that 38% of patients with mast cell disease also had hyperPOTS.

POTS patients may have low plasma, red cell or total blood volumes. One study found 28.9% of POTS patients to be hypovolemic, meaning they had less volume in their blood stream than normal. In some of these patients, they have low renin activity and aldosterone when standing. Others may have high angiotensin II levels. These molecules are related to regulation of blood pressure. GI conditions that result in poor oral water intake from nausea or diarrhea can cause hypovolemia with orthostatic intolerance and tachycardia. For this population, the recommendation is to consider POTS as secondary the GI condition.

POTS patients present with persistent tachycardia, reduced stroke volume (amount of blood pushed out of the heart), loss of mass in the left ventricle (this part of the heart is smaller than normal), and reduced peak oxygen uptake when standing, during and after exercise. These markers are also present in physical deconditioning, which can also cause orthostatic intolerance regardless of why the deconditioning occurred. For this reason, POTS is often associated with conditions that provoke exercise intolerance, such as fibromyalgia, chronic fatigue syndrome and deconditioning.

 

References:

Stewart, Julian M. Update on the theory and management of orthostatic intolerance and related syndromes in adolescents and children. Expert Rev Cardiovasc Ther 2012 November; 10(11): 1387-1399.

Figueroa, Juan J., et al. Preventing and treating orthostatic hypotension: As easy as A, B, C. Cleve Clin J Med 2010 May; 77(5): 298-306.

Benarroch, Eduardo E. Postural tachycardia syndrome: a heterogenous and multifactorial disorder. Mayo Clinic Proceedings 2012; 87(12): 1214-1225.

Cheung, Ingrid, Vadas, Peter. A new disease cluster: mast cell activation syndrome, postural orthostatic tachycardia syndrome and Ehlers-Danlos syndrome. J All Clin Immunol 2015: 135(2); AB65.

Joyner, M., Masuki, S. POTS versus deconditioning: the same or different? Clin Auton Res 2008 Dec; 18(6): 300-307.