Hypotension and Syncope

Orthostatic Hypotension

Standing upright displaces 500 to 800 mL of blood to the abdomen and lower extremities, thereby resulting in an abrupt drop in venous return to the heart. This drop leads to a decrease in cardiac output and stimulation of aortic, carotid, and cardiopulmonary baroreceptors, which triggers a reflex increase in sympathetic outflow. As a result, heart rate, cardiac contractility, and vascular resistance increase to maintain stable systemic blood pressure (BP) on standing. Orthostatic intolerance is a term used to refer to the signs and symptoms of an abnormality in any portion of this BP control system. Orthostatic hypotension is defined as a 20-mm Hg drop in systolic BP or a 10-mm Hg drop in diastolic BP within 3 minutes of standing. Orthostatic hypotension can be asymptomatic or associated with syncope, lightheadedness/presyncope, tremulousness, weakness, fatigue, palpitations, diaphoresis, and blurred or tunnel vision. Many patients with orthostatic hypotension are asymptomatic despite substantial falls in systolic BP and low upright BPs. These symptoms are often worse immediately on arising in the morning or after meals or exercise. Initial orthostatic hypotension is defined as less than a 40-mm Hg decrease in BP immediately on standing with rapid (<30 seconds) return to normal. ^{, ,} In contrast, delayed progressive orthostatic hypotension is characterized by a slow progressive decrease in systolic BP on standing. Syncope that occurs after meals, particularly in older adults, can result from a redistribution of blood to the gut. A decline in systolic BP of approximately 20 mm Hg approximately 1 hour after eating has been reported in up to one third of older adult nursing home residents. Although usually asymptomatic, it can result in lightheadedness or syncope.

Drugs that either cause volume depletion or result in vasodilation are the most common causes of orthostatic hypotension ( Table 71.3 ). Older adult patients are particularly susceptible to the hypotensive effects of drugs because of reduced baroreceptor sensitivity, decreased cerebral blood flow, renal sodium wasting, and an impaired thirst mechanism that develops with aging (see Chapter 90 ). Orthostatic hypotension can also result from neurogenic causes, which can be subclassified into primary and secondary autonomic failure (see Chapter 102 ). Primary causes are generally idiopathic, whereas secondary causes are associated with a known biochemical or structural anomaly or are seen as part of a particular disease or syndrome.

There are three types of primary autonomic failure. Pure autonomic failure (Bradbury-Eggleston syndrome) is an idiopathic sporadic disorder characterized by orthostatic hypotension, usually in conjunction with evidence of more widespread autonomic failure, such as disturbances in bowel, bladder, thermoregulatory, and sexual function. Patients with pure autonomic failure have reduced supine plasma norepinephrine levels. Multisystem atrophy (Shy-Drager syndrome) is a sporadic, progressive, adult-onset disorder characterized by autonomic dysfunction, parkinsonism, and ataxia in any combination. The third type of primary autonomic failure is Parkinson disease with autonomic failure. A small subset of patients with Parkinson disease may also experience autonomic failure, including orthostatic hypotension. In addition to these forms of chronic autonomic failure is a rare, acute panautonomic neuropathy. This neuropathy generally occurs in young people and results in severe, widespread sympathetic and parasympathetic failure with orthostatic hypotension, loss of sweating, disruption of bladder and bowel function, fixed heart rate, and fixed dilated pupils.

Postural orthostatic tachycardia syndrome (POTS) is a clinical syndrome characterized by frequent symptoms that occur with standing (e.g., lightheadedness, palpitations, tremulousness, generalized weakness, blurred vision, exercise intolerance, fatigue), an increase in heart rate of 30 beats/min or more on standing (or ≥40 beats/min in those 12 to 19 years of age), and absence of a more than 20-mm Hg reduction in systolic BP. ^{, ,} The precise pathophysiologic basis for POTS has not been well defined. Some patients have both POTS and NMS.

Reflex-Mediated Syncope

Reflex-mediated, or situational, causes of syncope are listed in Table 71.2 . In this group of conditions, the cardiovascular reflexes that control the circulation become inappropriate in response to a trigger, which results in vasodilation with or without bradycardia and a drop in BP and global cerebral hypoperfusion. In each case the reflex is composed of a trigger (the afferent limb) and a response (the efferent limb). This group of reflex-mediated syncopal syndromes has in common the response limb of the reflex, which consists of increased vagal tone and withdrawal of peripheral sympathetic tone and leads to bradycardia, vasodilation, and ultimately, hypotension, presyncope, or syncope. If hypotension secondary to peripheral vasodilation predominates, it is classified as a vasodepressor-type reflex response; if bradycardia or asystole predominates, it is classified as a cardioinhibitory response; and when both vasodilation and bradycardia play a role, it is classified as a mixed response. Specific triggers distinguish these causes of syncope. For example, micturition-induced syncope results from activation of mechanoreceptors in the bladder, defecation-induced syncope results from neural input from gut wall tension receptors, and swallowing-induced syncope results from afferent neural impulses arising from the upper gastrointestinal tract. The two most common types of reflex-mediated syncope, carotid sinus hypersensitivity and neurally mediated hypotension, are discussed later. Identification of the trigger is of importance because of its therapeutic implications, with avoidance of the trigger, where possible, preventing further syncopal episodes.

Neurally Mediated Hypotension or Syncope (Vasovagal Syncope)

The term neurally mediated hypotension or syncope (also known as neurocardiogenic, vasodepressor, and vasovagal syncope and “fainting”) has been used to describe a common abnormality in regulation of BP characterized by an abrupt onset of hypotension with or without bradycardia. Triggers associated with the development of NMS include orthostatic stress, such as can occur with prolonged standing or a hot shower, and emotional stress, such as can result from the sight of blood. ^{, ,} Neurally mediated hypotension has shown to run in families and three genes have been associated. While our understanding of the genetic basis for neurally mediated hypotension is in its early stages, this is an active area of research. A large proportion of patients with NMS may have minor psychiatric disorders. Patients with syncope caused by neurally mediated hypotension may also have psychogenic pseudosyncope. It has been proposed that NMS results from a paradoxical reflex that is initiated when ventricular preload is reduced by venous pooling. This reduction leads to a decrease in cardiac output and BP, which is sensed by arterial baroreceptors. The resultant increased catecholamine levels, combined with reduced venous filling, leads to a vigorously contracting, volume-depleted ventricle. The heart itself is involved in this reflex by virtue of the presence of mechanoreceptors, or C fibers, consisting of nonmyelinated fibers found in the atria, ventricles, and pulmonary artery. It has been proposed that vigorous contraction of a volume-depleted ventricle leads to activation of these receptors in susceptible individuals. These afferent C fibers project centrally to the dorsal vagal nucleus of the medulla and can result in “paradoxical” withdrawal of peripheral sympathetic tone and an increase in vagal tone, which in turn causes vasodilation and bradycardia. The ultimate clinical consequence is syncope or presyncope. It has been speculated that the fall in BP seen during neurally mediated hypotension mimics a “fictitious hemorrhage.” To protect against this fictitious hemorrhage, the brainstem triggers cardioinhibition as protection against the hypothetical loss of blood simulated by the reduction in venous return. The most effective solution to stopping blood loss is to stop the heart. A recent study has shown that in patients who experienced a syncopal episode during a tilt-table test there was sympathetic activation before a syncopal event followed by sympathetic withdrawal and parasympathetic activation. Not all NMS, however, results from activation of mechanoreceptors. In humans the sight of blood or extreme emotion can trigger syncope, thus suggesting that higher neural centers can also participate in the pathophysiology of vasovagal syncope. In addition, central mechanisms can contribute to the production of NMS.

Carotid Sinus Hypersensitivity

Syncope caused by carotid sinus hypersensitivity results from stimulation of carotid sinus baroreceptors located in the internal carotid artery above the bifurcation of the common carotid artery. It is diagnosed by the reproduction of clinical syncope during carotid sinus massage, with a cardioinhibitory response if asystole is longer than 3 seconds or AV block occurs; or a significant vasodepressor response if there is a more than 50-mm Hg drop in systolic BP; or a mixed cardioinhibitory and vasodepressor response. Carotid sinus hypersensitivity is detected in approximately one third of older adult patients evaluated for syncope or falls. It is important, however, to recognize that carotid sinus hypersensitivity is also frequently observed in asymptomatic older adult patients. Thus the diagnosis of carotid sinus hypersensitivity should be approached cautiously after excluding alternative causes of the syncope. Once diagnosed, dual-chamber pacemaker implantation is recommended for patients with recurrent syncope or falls resulting from carotid sinus hypersensitivity that is cardioinhibitory or mixed (class 2A/IIa, level of evidence [LOE] B-R). ^{, ,}