Heart Rate Variability
Heart rate variability is defined as beat-to-beat variation in the heart rate or R-R interval on the electrocardiogram (
ECG).
5 In order to assess heart rate variability, standardized breathing techniques are of paramount importance as heart rate changes often occur in concert with the cycle of breathing: so-called “respiratory sinus arrhythmia” in which the heart rate increases with respiration and decreases with expiration.
6 This can be achieved by nine cycles of maximal effort deep breathing when 5 seconds is allowed for both inspiration and expiration, or “paced breathing.” Maximal effort must be provided in order to accurately interpret changes in heart rate. These changes are compared to standardized data that account for age and gender. Variability in heart rate declines with age, though diminished
variability may also be seen in parasympathetic dysfunction, such as in Parkinson disease (PD).
4 Variability is also reduced in cardiac disease states with sympathetic overdrive, such as congestive heart failure (
CHF).
7
Additionally, variability in the R-R interval on
ECG can be evaluated with the “30:15” ratio. Originally studied in diabetic patients with autonomic neuropathy, the 30:15 ratio evaluates the R-R interval at 15 seconds and 30 seconds after standing.
8 Normal ratios are greater than 1.05, and high values are seen as a normal vagal response.
9 This test can also be useful in the evaluation of patients with orthostatic hypotension or postural orthostatic tachycardia syndrome (
POTS).
4
Valsalva Maneuver
The Valsalva maneuver (ie, forced expiration against a closed glottis) evaluates both the sympathetic and parasympathetic response of the baroreflex in four unique phases. In phase I during forced expiration (˜40 mm Hg), an increase in blood pressure is noted because of increased intrathoracic pressure compressing the aorta and inferior vena cava. Phase II occurs during the later component of expiration and has a distinct early and late profile. In early phase II, there is decreased cardiac output and blood pressure because of continued compression of the inferior vena cava causing reduced preload and venous return. Heart rate increases reflexively during early phase II. In late phase II, systemic vascular resistance increases as a result of baroreflex activation and increased adrenergic tone. The onset of phase III occurs at end expiration (ie, with cessation of forced expiration), producing an abrupt decrease in blood pressure related to reduced intrathoracic pressure. In phase IV, there is an increase in blood pressure because of sustained vasocontriction and increased cardiac output from restoration of venous return, reflecting elevated adrenergic tone. Additionally, there is a decrease in heart rate as a result of the baroreflex.
4,
9,
10 The Vasalva maneuver and associated hemodynamic changes are depicted in
Figure 28.1.
The parasympathetic nervous system is evaluated by the Valsalva ratio, which is defined as the maximum heart rate achieved during the study divided by the lowest heart rate recorded within 30 seconds of the maximum value.
11 A higher Valsalva ratio is indicative of a healthy parasympathetic response, implying intact heart rate variability.
4 Typically, a value below 1.2 is considered abnormal.
12
In order to assess the sympathetic nervous system, the blood pressure response to late phase II and IV is analyzed. Normal sympathetic responses would include recovery of blood pressure in late phase II (4-7 seconds after phase I) to the baseline value and an increase in blood pressure over the baseline value in phase IV.
4 Patients with mild disease have an absent or reduced late phase II response and reduced phase IV
hypertensive response. Moderate sympathetic dysfunction causes absent late phase II and reduced phase IV responses and typically mild orthostatic hypotension. In patients with severe sympathetic failure, there is an exaggerated phase II hypotensive response with absent late phase II and phase IV hypertensive responses.
13 The degree of sympathetic dysfunction as defined by blood pressure responses to late phase II and phase IV of the Valsalva maneuver is summarized in
Table 28.1.
Variations in the results of the Valsalva maneuver can be useful in differentiating various disorders. Neurogenic orthostatic hypotension creates a “V” blood pressure response pattern as a prolonged and exaggerated decrease in blood pressure in phase II with a reduced to absent response in phase III. Inappropriate sinus tachycardia produces an “M” blood pressure response pattern with two systolic peaks (phase II and IV). In
POTS, there is an “N” pattern with a sustained overshoot in blood pressure of more than or equal to 10 mm Hg during phase IV.
14
Cardiovascular autonomic neuropathy (
CAN) in patients with diabetes has historically been evaluated with five cardiovascular reflex tests, including deep breathing testing, Valsalva maneuver, 30/15 test, handgrip test, and orthostatic hypotension test. However, the utility of the handgrip test has been questioned, as its result is more likely to be abnormal with an elevated resting diastolic blood pressure (
DBP). Additionally, it is unlikely to be positive in the setting of baseline hypertension.
15
Combining the Valsalva maneuver with lying to standing deep breathing testing has been suggested as an initial screening test for early autonomic neuropathy, with a sensitivity of 85%.
16 Additionally, in a study of patients with type 1 diabetes, combining at least two cardiovascular autonomic reflex tests had a sensitivity of 100% in detecting autonomic dysfunction, when using radiotracer iodine-123
MIBG testing as a reference standard.
17
Tilt-Table Test
Tilt-table test is a commonly used tool to evaluate the sympathetic and parasympathetic system and is useful in the diagnosis of diseases such as orthostatic hypotension,
POTS, and neurocardiogenic syncope.
18,
19 The role of the tilt-table test is to evaluate the neurocardiovascular system response to shifts in blood volume. Changes in posture from lying to standing result in 400 to 600 mL of blood shifting from the thorax into the lower extremities by gravitational stress.
20 Hypotension and syncope are prevented by venous contraction by skeletal muscles in the lower extremities and neurocardiogenic baroreflex responses. In active standing, both of these mechanisms are engaged; however, tilt-table test isolates the neurocardiogenic response by removing the active phase of standing.
4
Patients are initially secured to the table in the supine position and should be attached to an automated external defibrillator with pacing capabilities. The patient is kept in the supine position for approximately 20 minutes to obtain a baseline blood pressure and heart rate. Once the patient is in a supine steady state, the table angle is rapidly increased to a head-up position of 60 to 80 degrees. In order to effectively assess the baroreceptors, patients should stay as still as possible and avoid moving their legs to prevent skeletal muscle-mediated vasoconstriction. The environment should be calm and quiet to avoid central neurologic effects. Patients remain in the head-up position for at least 10 minutes, with continuous heart rhythm monitoring and frequent blood pressure assessments every 2 to 3 minutes. The test may need to be discontinued prematurely if the patient develops severe discomfort, sustained hypotensive response, or syncope.
4
In adults, a normal response to tilt-table test includes a mild heart rate increase of no more than 30 bpm, systolic blood pressure (
SBP) decrease of no more than 20 mm Hg, and a
DBP decrease of no more than 10 mm Hg.
18 Patients with orthostatic hypotension exhibit a fall in blood pressure (ie,
SBP >20 mm Hg or
DBP >10 mm Hg) with a blunted heart rate response. In
POTS, patients will have an exaggerated heart rate response (sustained increase of heart rate by at least 30 bpm) with a normal blood pressure response. Neurocardiogenic syncope exhibits an abrupt fall in blood pressure without a compensatory heart rate response and may exhibit asystole. This response may occur late (up to 20 minutes) into the head-up maneuver.
4,
10,
18 Figure 28.2 provides examples of the various hemodynamic responses expected during tilt-table test.
Table 28.2 outlines the classification of responses to a positive tilt-table test.
Tilt-table test is time consuming and may take at least 45 minutes to complete the study. In order to facilitate a vasovagal response, isoproterenol may be infused at a rate of 0.05 µg/kg/min with a maximum dose of 5 µg/min, spending 10 minutes at the 70-degree head-up position. When compared to standard tilt-table test, the specificity is slightly reduced from 91% to 83% with isoproterenol infusion, though it had a significantly higher ability to induce a vasovagal response (9% in passive tilt table vs. 17% with isoproterenol).
21
The “Italian Protocol” is an alternative approach that utilizes sublingual nitroglycerin during tilt-table test and has a reported sensitivity of 62% and specificity of 92%. This protocol has a stabilization phase, passive phase, provocation phase, and finally
completion of the study with test interruption. In the stabilization phase, the patient is kept in the supine position for 5 minutes. During the passive phase, the patient is kept at 60 degree for 20 minutes. In the provocation phase, the patient is administered 400 µg of sublingual nitroglycerin spray and monitored for 15 minutes. The test is completed or interrupted if there is syncope, the development of progressive orthostatic hypotension lasting more than 5 minutes, or if no symptoms are reproduced.
22
Carotid Sinus Massage
The
CSM is useful in evaluating the parasympathetic nervous system and carotid sinus baroreceptors. The study should not be performed in patients with carotid stenosis, and patients should undergo continuous
ECG recording to assess for heart block or asystole. It is performed by unilateral compression of the carotid sinus for 20 to 30 seconds, followed by releasing compression for a few minutes and repeating compression on the contralateral carotid sinus.
9 The diagnosis of carotid sinus hypersensitivity can be made if asystole occurs for more than 3 seconds, atrioventricular block occurs, a 50 mm Hg or more drop in
SBP consistent with a vasodepressor response occurs, or a mixed cardioinhibitory or vasodepressor response occurs.
23 The effect of
CSM may also be helpful in delineating the level of atrioventricular block in the setting of second-degree atrioventricular block. Right
CSM has a preferential effect on the sinus node, whereas left
CSM has a great effect on the atrioventricular node.
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