Standardized Autonomic Reflex Research Articles

Interpreting resting heart rate variability in complex populations: the role of autonomic reflexes and comorbidities.

Resting heart rate variability (HRV) is an important biomarker linking mental health to cardiovascular outcomes. However, resting HRV is also impaired in autonomic neuropathy, a common and underdiagnosed complication of common medical conditions which is detected by testing autonomic reflexes. We sought to describe the relationship between autonomic reflex abnormalities and resting HRV, taking into consideration medical comorbidities and demographic variables. Participants (n=209) underwent a standardized autonomic reflex screen which was summarized as the Composite Autonomic Severity Score (CASS) and included measures of reflexive HRV, e.g., heart rate with deep breathing (HRDB). Resting HRV measures were: pNN50 (percentage of NN intervals that differ by>50ms) and cvRMSSD (adjusted root mean square of successive differences). In univariate analyses, lower resting HRV was associated with: older age, higher CASS, neuropathy on examination, hypertension, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, and psychiatric disease. Adaptive regression spline analysis revealed that HRDB explained 27% of the variability in resting HRV for participants with values of HRDB in the normal range. Outside this range, there was no linear relationship because: (1) when HRDB was low (indicating autonomic neuropathy), resting HRV was also low with low variance; and (2) when HRDB was high, the variance in resting HRV was high. In multivariate models, only HRDB was significantly independently associated with cvRMSSD and pNN50. Subclinical autonomic neuropathy, as evidenced by low HRDB and other autonomic reflexes, should be considered as a potential confounder of resting HRV in research involving medically and demographically diverse populations.

Natural History of Afferent Baroreflex Failure in Adults.

To describe the natural history of afferent baroreflex failure (ABF) based on systematic review of clinical and laboratory data in patients with a diagnosis of ABF at Mayo Clinic Rochester. We performed a retrospective chart review of all patients who underwent standardized autonomic reflex testing between 2000 and 2020 and had confirmation of the diagnosis of ABF by an autonomic disorders specialist. Patients were identified using a data repository of medical records. Variables included demographic, all-cause mortality, medications, ABF manifestations, comorbidities, and laboratory (autonomic testing, blood pressure monitoring, echocardiogram, brain imaging, plasma catecholamines, serum sodium level, and kidney function tests). A total of 104 patients with ABF were identified. Head and neck radiation was the most common etiology (86.5%), followed by neck surgery (5.8%) and other causes (7.7%). The most common findings were hypertension (87.5%), fluctuating blood pressure (78.8%), orthostatic hypotension (91.3%), syncope (58.6%), headache (22.1%), and tachycardia (20.2%). Patients commonly received antihypertensives (66.3%), pressor agents (41.3%), or a combination of both (19.2%). The median latency from completion of radiation to ABF was longer compared to the latency in the surgery group (p < 0.0001). Comorbidities, including complications from neck radiation, were frequently seen and all-cause mortality was 39.4% over a 20-year period. ABF should be suspected in patients with prior head and neck cancer treated by radiation or surgery who present with labile hypertension and orthostatic hypotension. Management may require both antihypertensive and pressor medications. The morbidity and mortality in ABF are high.

Low-frequency facial hemodynamic oscillations distinguish migraineurs from non-headache controls.

Surface imaging is a promising, noninvasive approach to assess regional perfusion in craniovascular disorders such as migraine. We used optical imaging to examine differences in facial blood volume at baseline and in response to ammonia inhalation (a noxious stimulus), as well as standardized measures of cardiovascular autonomic function, in healthy, non-headache controls (n = 43) and in interictal migraine subjects (n = 22). Resting facial cutaneous oscillation (FCO) frequency was significantly different in migraine compared to healthy controls. Following ammonia inhalation, healthy controls showed a significant increase in resting FCO frequency, whereas this response was not significant in the migraine group. Standardized autonomic reflex parameters did not differ significantly between study groups, and facial cutaneous activity did not correlate with standardized cardiovascular autonomic reflex parameters, suggesting potentially different regulation. This approach to the assessment of craniofacial hemodynamic function appears to exhibit differing mechanisms from previously available techniques, and represents a promising new physiological biomarker for the study of craniofacial vascular function in migraine and potentially other craniovascular disorders.

Disturbances of gastrointestinal transit and autonomic functions in postural orthostatic tachycardia syndrome.

Gastrointestinal symptoms are common in the postural orthostatic tachycardia syndrome (POTS). However, few studies have evaluated gastrointestinal transit in POTS. Our primary objectives were to evaluate gastrointestinal emptying and the relationship with autonomic dysfunctions in POTS. We reviewed the complete medical records of all patients aged 18 years and older with POTS diagnosed by a standardized autonomic reflex screen who also had a scintigraphic assessment of gastrointestinal transit at Mayo Clinic Rochester between 1998 and 2012. Associations between specific gastric emptying and autonomic (i.e., cardiovagal, adrenergic, and sudomotor) disturbances were evaluated. Among 163 patients (140 women, mean [± SEM] age 30 [± 1] years), 55 (34%) had normal, 30 (18%) had delayed, and 78 (48%) had rapid gastric emptying. Fifty-eight patients (36%) had clinical features of physical deconditioning, which was associated (p = 0.02) with rapid gastric emptying. Associations with delayed gastric emptying included vomiting, which was more common (p < 0.003), and anxiety or depression, which was less common (p = 0.02). The tilt-associated increase in heart rate and reduction in systolic BP at 1 min was associated (p < 0.05), being greater in patients with delayed gastric emptying. Two-thirds of patients with POTS and GI symptoms had abnormal, most frequently rapid gastric emptying. Except for more severe adrenergic impairment in patients with delayed gastric emptying, the pattern of autonomic dysfunction did not discriminate among gastric emptying groups. Further studies are necessary to ascertain whether extravascular volume depletion and/or deconditioning contribute to POTS in patients with gastrointestinal symptoms.

Autonomic dysfunction in chronic inflammatory demyelinating polyradiculoneuropathy

Autonomic deficits in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have not been adequately quantitated. The Composite Autonomic Severity Score (CASS) is a validated instrument for laboratory quantitation of autonomic failure derived from standard autonomic reflex tests. We characterized dysautonomia in CIDP using CASS. Autonomic function was retrospectively analyzed in 47 patients meeting CIDP criteria. CASS ranges from 0 (normal) to 10 (pandysautonomia), reflecting summation of sudomotor (0-3), cardiovagal (0-3), and adrenergic (0-4) subscores. Severity of neurologic deficits was measured with Neuropathy Impairment Score (NIS). Degree of small fiber involvement was assessed with quantitative sensation testing. Thermoregulatory sweat test (TST) was available in 8 patients. Patients (25 men) were middle-aged (45.0 ± 14.9 years) with longstanding CIDP (3.5 ± 4.3 years) of moderate severity (NIS, 46.5 ± 32.7). Autonomic symptoms were uncommon, mainly gastrointestinal (9/47; 19%) and genitourinary (8/47; 17%). Autonomic deficits (CASS ≥1) were frequent (22/47; 47%) but very mild (CASS, 0.8 ± 0.9; CASS ≤3, all cases). Deficits were predominantly sudomotor (16/47; 34%) and cardiovagal (10/47; 21%) with relative adrenergic sparing (4/47; 9%). TST was abnormal in 5 of 8 patients (anhidrosis range, 2%-59%). Sudomotor impairment was predominantly distal and postganglionic. Somatic deficits (disease duration, severity, small fiber deficits) did not predict presence of autonomic deficits. Our data characterize the autonomic involvement in classic CIDP as mild, cholinergic, and predominantly sudomotor mainly as a result of lesions at the distal postganglionic axon. Extensive or severe autonomic involvement (CASS ≥4) in suspected CIDP should raise concern for an alternative diagnosis.

CARDIOVASCULAR AUTONOMIC REGULATION IN SUBJECTS WITH NORMAL BLOOD PRESSURE, HIGH–NORMAL BLOOD PRESSURE and RECENT‐ONSET HYPERTENSION

1. In the present study, we tested the hypothesis that heart rate variability (HRV) is reduced in recent-onset hypertension and that pressor responses to standard autonomic reflex tests are not any different in hypertensives compared with normotensives. We also hypothesized that subjects with high-normal blood pressure (BP) would be distinguishable from normotensives on the basis of short-term HRV indices. 2. Three groups of subjects, each consisting of 15 men and 10 women, were examined. The first group consisted of subjects with recent-onset hypertension who were not taking antihypertensive medication (mean (+/-SD) age 50 +/- 12 years; BP >/= 140/90 mmHg), the second group consisted of subjects with high-normal BP (mean age 46 +/- 13 years; BP 130-139/85-89 mmHg) and the third group consisted of subjects with normal BP (mean age 48 +/- 12 years; BP < 120/80 mmHg). The aim was to characterize the autonomic state in each group. 3. Blood pressure, heart rate (HR), indices of short-term HRV during supine rest and quiet standing, HR variation during timed deep breathing (HRVdb) and pressor responses to the cold pressor test and sustained isometric handgrip were compared between the groups. 4. Although the three groups were comparable (P > 0.1) in terms of mean HR and low-frequency (LF) power expressed in normalized units at rest and during quiet standing, the standard deviation of normal-to-normal RR intervals (SDNN) during supine rest, LF and high-frequency spectral powers during supine rest and HRVdb were lowest in hypertensives (P </= 0.05 for each), indicating diminished baroreflex modulation of RR intervals in hypertensives. 5. In contrast, LF power was highest in subjects with high-normal BP (P </= 0.05) during supine rest and this is possibly because of higher BP variability. 6. The results suggest that HRVdb provides a simple measure of cardiac vagal effects in hypertensives, the rate-pressure product provides a simple measure of overall HRV in hypertensives and, in clinical hypertension, the arterial baroreflex mechanism is reset to maintain a higher BP through diminished vagal modulation of HR and possibly heightened sympathetic outflow to the heart and resistance vessels.

In vivo cardiovascular effects of the new atypical neuroleptic sertindole

INTRODUCTION: The goal of this open clinical study was to perform a detailed investigation of the cardiovascular effects of the novel atypical neuroleptic sertindole. METHOD: Thirty initially untreated schizophrenic inpatients (diagnosed according to DSM-III-R) underwent a total of 103 serial recordings of standardized autonomic tests during a sertindole dose titration programme (4-16 mg/d). The autonomic test battery included: (1) conventional ECGs with 12 channels, (2) computer-assisted analysis of the 5-min resting heart rate variability (HRV); (3) HRV during standard autonomic reflex tests (deep breathing test, 30:15 ratio); and (4) blood pressure measurement under resting conditions and during orthostatic stress (Schellong test). Reference values for the HRV study were obtained from healthy controls ( n =80). RESULTS: The most important findings were: (1) sertindole significantly increased the resting heart rate; (2) sertindole induced a significant and probably dose-dependent prolongation of the frequency-corrected QT-times, while mean PQ-conduction times remained unchanged; (3) sertindole had no significant effects on autonomic parasympathetic tone, both in the resting study and following the autonomic reflex tests; and (4) sertindole at doses between 4 and 16 mg/d did not significantly influence blood pressure either under resting conditions or during orthostatic stress. CONCLUSION: The implications of these findings for the cardiovascular safety and tolerance of sertindole are discussed comprehensively, while considering the pathophysiologically relevant mechanisms underlying the appearance of life-threatening cardiac arrhythmias and sudden cardiac death. ( Int J Psych Clin Pract 2001; 5:33-40)