Synchronous monitoring of brain-heart electrophysiology using heart rate variability coupled with rapid quantitative electroencephalography in orthostatic hypotension patients with α-synucleinopathies: Rapid prediction of orthostatic hypotension and preliminary exploration of brain stimulation therapy.

BACKGROUND: In α-synucleinopathies, the dysfunction of the autonomic nervous system which typically manifests as orthostatic hypotension (OH) often leads to severe consequences and poses therapeutic challenges. This study aims to discover the brain-cardiac electrophysiological changes in OH patients with α-synucleinopathies using the rapid quantitative electroencephalography (qEEG) coupled with heart rate variability (HRV) technique to identify rapid, noninvasive biomarkers for early warning and diagnosis, as well as shed new light on complementary treatment approaches such as brain stimulation targets. METHODS: In this study, 26 subjects of α-synucleinopathies with OH (α-OH group), 21 subjects of α-synucleinopathies without OH (α-NOH group), and 34 healthy controls (control group) were included from September 2021 to August 2023 (NCT05527067). The heart rate-blood pressure variations in supine and standing positions were monitored, and synchronization parameters of seated resting-state HRV coupled with qEEG were collected. Time-domain and frequency-domain of HRV measures as well as peak frequency and power of the brainwaves were extracted. Differences between these three groups were compared, and correlations between brain-heart parameters were analyzed. RESULTS: The research results showed that the time-domain parameters such as MxDMn, pNN50, RMSSD, and SDSD of seated resting-state HRV exhibited a significant decrease only in the α-OH group compared to the healthy control group (p < 0.05), while there was no significant difference between the α-NOH group and the healthy control group. Several time-domain and frequency-domain parameters of seated resting-state HRV were found to be correlated with the blood pressure changes within the first 5 min of transitioning from supine to standing position (p < 0.05). Differences were observed in the power of beta1 waves (F4 and Fp2) and beta2 waves (Fp2 and F4) in the seated resting-state qEEG between the α-OH and α-NOH groups (p < 0.05). The peak frequency of theta waves in the Cz region also showed a difference (p < 0.05). The power of beta2 waves in the Fp2 and F4 brain regions correlated with frequency-domain parameters of HRV (p < 0.05). Additionally, abnormal electrical activity in the alpha, theta, and beta1 waves was associated with changes in heart rate and blood pressure within the first 5 min of transitioning from supine to standing position (p < 0.05). CONCLUSION: Rapid resting-state HRV with certain time-domain parameters below normal levels may serve as a predictive indicator for the occurrence of orthostatic hypotension (OH) in patients with α-synucleinopathies. Additionally, the deterioration of HRV parameters correlates with synchronous abnormal qEEG patterns, which can provide insights into the brain stimulation target areas for OH in α-synucleinopathy patients.

A therapeutic challenge relating to the association of orthostatic hypotension and supine hypertension in a patient with cardiac autonomic neuropathy: a case report.

BACKGROUND: Cardiac autonomic neuropathy is a highly prevalent pathology in the diabetic population, and is the leading cause of death in this population. Orthostatic hypotension is the main clinical manifestation of the disease. In some patients, this orthostatic hypotension is associated with supine hypertension, posing a therapeutic challenge since treatment of one entity may aggravate the other. The challenge is to manage each of these two hemodynamic opposites without exposing the patient to a life-threatening risk of severe hypotension or hypertension. CASE PRESENTATION: We report a case of a 62-year-old ethnic Moroccan woman who has cardiovascular risk factors such as type 2 diabetes, arterial hypertension, and dyslipidemia. The patient's symptoms included dizziness, tremors, morning sickness, palpitations, and intolerance to exertion. Given her symptomatology, the patient benefited from an exploration of the autonomic nervous system through cardiovascular reactivity tests (Ewing tests), which confirmed the diagnosis of cardiac autonomic neuropathy. In addition to orthostatic hypotension, our patient had supine arterial hypertension, complicating management. To treat orthostatic hypotension, we advised the patient to avoid the supine position during the day, to raise the head of the bed during the night, and to have a sufficient fluid intake, with a gradual transition from decubitus to orthostatism and venous restraint of the lower limbs. Supine hypertension was treated with transdermal nitrates placed at bedtime and removed 1 hour before getting up. One week after the introduction of treatment, the patient reported a clear regression of functional symptoms, with an improvement in her quality of life. Improvement in symptomatology was maintained during quarterly follow-up consultations. CONCLUSIONS: Cardiac autonomic neuropathy is a very common pathology in diabetic patients. It is a serious condition with a life-threatening prognosis. Its management must be individualized according to the symptomatology and profile of each patient. The treatment of patients with orthostatic hypotension and supine hypertension requires special attention to ensure that each entity is treated without aggravating the other.

The effect of lower limb strengthening exercise on orthostatic blood pressure and the skeletal muscle pump in older people with orthostatic hypotension.

INTRODUCTION: Activation of muscles during standing is recommended to activate the skeletal muscle pump, increasing venous return and increasing blood pressure (BP) in people with orthostatic hypotension (OH). AIM: The aim of this study is to determine if increasing the strength of the lower limb muscles can improve the effectiveness of the venous pump and postural BP in older people with OH. METHODS: Ten older people with OH underwent an 8-week lower limb strengthening intervention. Repeated measurements of orthostatic BP, calf venous ejection fraction (EF) and muscle strength took place before, during and after intervention. RESULTS: The intervention increased calf muscle strength by 21% (interquartile range: 18-28), p = 0.018, from a median baseline of 38 (34-45) kg. Participants had normal levels of venous EF 64% (51-75) at baseline, with little to no venous reflux. The median ejection volume at baseline was 44 (36-58) mL per calf. Despite increasing muscle strength, venous EF did not increase (percentage change -10% (-16 to 24), p = 0.8) and systolic BP drop did not improve (percentage change 0% (-17 to 16), p = 1.0). Similarly, visual analysis of individual case-series trends revealed increasing muscle strength with no clinically meaningful change in EF or orthostatic BP. CONCLUSIONS: Muscle strengthening exercise does not increase the effectiveness of the skeletal muscle pump and is not an efficacious intervention for OH. As there is little to no venous pooling in the calf during standing in older people with OH, below knee compression is unlikely to be clinically effective.

Tilt table testing, methodology and practical insights for the clinic.

Tilt table testing (TTT) has been used for decades to study short-term blood pressure (BP) and heart rate regulation during orthostatic challenges. TTT provokes vasovagal reflex in many syncope patients as a background of widespread use. Despite the availability of evidence-based practice syncope guidelines, proper application and interpretation of TTT in the day-to-day care of syncope patients remain challenging. In this review, we offer practical information on what is needed to perform TTT, how results should be interpreted including the Vasovagal Syncope International Study classification, why syncope induction on TTT is necessary in patients with unexplained syncope and on indications for TTT in syncope patient care. The minimum requirements to perform TTT are a tilt table with an appropriate tilt-down time, a continuous beat-to-beat BP monitor with at least three electrocardiogram leads and trained staff. We emphasize that TTT remains a valuable asset that adds to history building but cannot replace it, and highlight the importance of recognition when TTT is abnormal even without syncope. Acknowledgement by the patient/eyewitness of the reproducibility of the induced attack is mandatory in concluding a diagnosis. TTT may be indicated when the initial syncope evaluation does not yield a certain, highly likely, or possible diagnosis, but raises clinical suspicion of (1) reflex syncope, (2) orthostatic hypotension (OH), (3) postural orthostatic tachycardia syndrome or (4) psychogenic pseudosyncope. A therapeutic indication for TTT in the patient with a certain, highly likely or possible diagnosis of reflex syncope, may be to educate patients on prodromes. In patients with reflex syncope with OH TTT can be therapeutic to recognize hypotensive symptoms causing near-syncope to perform physical countermanoeuvres for syncope prevention (biofeedback). Detection of hypotensive susceptibility requiring therapy is of special value.

Advances in non-pharmacological management of Parkinson's disease complicated with blood pressure abnormalities.

Parkinson's disease (PD) often presents with autonomic dysregulation, leading to blood pressure irregularities such as neurogenic orthostatic hypotension (nOH), neurogenic supine hypertension (nSH), and postprandial hypotension (PPH). Unfortunately, these conditions remain prevalent and receive insufficient attention in scientific discourse. They not only cause complications like syncope, falls, and fractures but also result in long-term damage to vital organs, diminishing patients' quality of life. Early implementation of appropriate non-pharmacologic management is crucial to prevent severe adverse events later on. This review focuses on the types, clinical characteristics, mechanisms, and common non-pharmacologic management measures for PD complicated by abnormal blood pressure. By promoting early diagnosis, recognizing symptoms of abnormal blood pressure, and employing non-pharmacologic interventions such as health education, dietary adjustments, exercise, and Chinese medicine techniques, we aim to improve patients' symptoms and quality of life while providing practical guidance for managing PD-related blood pressure abnormalities.

Exploring the impact of caring for an individual with neurogenic orthostatic hypotension: a qualitative study.

Aim: This study aimed to explore the impact of caring for an individual with neurogenic orthostatic hypotension (nOH). Methods: Informal caregivers of individuals with nOH and either Parkinson's disease, multiple system atrophy, pure autonomic failure or dementia with Lewy bodies completed semi-structured interviews. Data were analyzed using thematic analysis; the identified concepts were used to develop a conceptual model. Results: Twenty informal caregivers were interviewed. Analysis identified several areas of caregiver impact due to nOH including impact on their time, particularly a need to supervise the patient to prevent falls as well as a lack of freedom and negative physical, work and social impacts. Many reported negative emotional impacts, including worry, stress or fear about the patient falling, depression and frustration. The conceptual model shows the relationships between concepts. Conclusion: The results highlight the wide-ranging impact of nOH, and the specific impact of the fear of falls on informal caregivers' lives.

Neurogenic orthostatic hypotension (nOH) is a type of hypotension (low blood pressure) which causes your blood pressure to fall when you stand up, meaning you can feel dizzy or lightheaded. This study looked at the experience of family members who provide day-to-day caregiving support to someone who has nOH as well as another condition which affects the brain and nerves (neurological condition). These neurological conditions included Parkinson's disease, multiple system atrophy, pure autonomic failure or dementia with Lewy bodies. Interviews were conducted with informal caregivers (family members) of people with nOH. Caregivers discussed a range of ways in which caring for their family member impacts them, including needing to supervise their family member to make sure they do not fall, as well as having a lack of freedom and feeling worried, stressed, depressed and frustrated.

Diagnosis and Management of Supine and Nocturnal Hypertension in Orthostatic Hypotension: A Review.

The prevalence of supine and nocturnal hypertension (S-N-HT) is high among patients with orthostatic hypotension (OH), especially in those who have a neurogenic aetiology. The evidence suggests that S-N-HT exacerbates OH, although it is unclear whether pharmacologic treatment of S-N-HT will improve OH. S-N-HT has also been associated with target organ damage. Therefore, assessment and management of S-N-HT should be an integral part of managing OH, but it is often overlooked in clinical practice.

Short-term Outcomes of Hypertensive Crises in Patients with Orthostatic Hypotension.

Supine hypertension-orthostatic hypotension disease poses a management challenge to clinicians. Data on short term outcomes of patients with orthostatic hypotension (OH) who are hospitalized with hypertensive (HTN) crises is lacking. The Nationwide Readmission Database 2016-2019 was queried for all hospitalizations of HTN crises. Hospitalizations were stratified according to whether OH was present or not. We employed propensity score to match hospitalizations for patients with OH to those without, at 1:1 ratio. Outcomes evaluated were 30-days readmission with HTN crises or falls, as well as hospital outcomes of in-hospital mortality, acute kidney injury, acute congestive heart failure, acute coronary syndrome, type 2 myocardial infarction, aortic dissection, stroke, length of stay (LOS), discharge to nursing home and hospitalization costs. We included a total of 9451 hospitalization (4735 in the OH group vs 4716 in the control group). OH group was more likely to be readmitted with falls (Odds ratio [OR]:3.27, P < 0.01) but not with HTN crises (P = 0.05). Both groups had similar likelihood of developing acute kidney injury (P = 0.08), stroke/transient ischemic attack (P = 0.52), and aortic dissection (P = 0.66). Alternatively, OH group were less likely to develop acute heart failure (OR:0.54, P < 0.01) or acute coronary syndrome (OR:0.39, P < 0.01) in the setting of HTN crises than non-OH group. OH group were more likely to have longer LOS and have higher hospitalization costs. Patients with OH who are admitted with HTN crises tend to have similar or lower HTN-related complications to non-OH group while having higher likelihood of readmission with falls, LOS and hospitalization costs. Further studies are needed to confirm such findings.

Effect of robotic tilt table verticalization on recovery in patients with disorders of consciousness: a randomized controlled trial.

Verticalization is a common therapeutic intervention during rehabilitation of patients with disorders of consciousness (DoC). The Erigo®Pro is a robotic tilt-table (RTT) with built-in stepping unit for the lower extremities to prevent orthostatic hypotension during verticalization. In addition, the system also provides functional electrical stimulation (FES) of muscles of the lower extremities. In this randomized controlled clinical trial (RCT), 47 patients with subacute DoC received a 4-week verticalization regime (16 verticalization sessions) and were allocated to one of three experimental groups: (1) verticalization by means of RTT with FES, (2) by means of RTT without FES, or (3) by conventional physiotherapy (CPT). Level of consciousness (LoC), spasticity, functional independence in daily activities, and functional brain connectivity measured by means of high-density quantitative EEG were assessed at baseline, directly after the verticalization program and after 6 months. There was a similar clinical improvement in all three experimental groups. RTT was not associated with an effect on any of the clinical outcomes. Verticalization or mobilization time during the study period was significantly positively correlated with recovery of consciousness (rho = 0.494, p < 0.001) in the short term and showed a statistical trend at the 6 months follow-up (rho = 0.244, p = 0.078). In conclusion, RTT treatment is not more effective in promoting recovery of consciousness than CPT in subacute DoC patients. Yet, our data suggest, that verticalization may be an important and feasible rehabilitation intervention in this group of patients. ClinicalTrials.gov NCT Number NCT02639481, registered on December 24, 2015.

Effect of Lower Limb vs. Abdominal Compression on Mobility in Orthostatic Hypotension: A Single-Blinded, Randomized, Controlled, Cross-Over Pilot Study in Parkinson's Disease.

BACKGROUND: Orthostatic hypotension (OH) in Parkinson's disease (PD) is frequent and associated with impairments in quality of life and reduced activities of daily living. Abdominal binders (AB) and compression stockings (CS) have been shown to be effective non-pharmacological treatment options. OBJECTIVE: Here, we investigate the effect of AB versus CS on physical activity using a digital mobility outcome (sit to stand [STS] frequency) collected in the usual environment as a primary endpoint. METHODS: We enrolled 16 PD patients with at least moderate symptomatic OH. In a randomized, single-blinded, controlled, crossover design, participants were assessed without OH treatment over 1 week (baseline), then were given AB or CS for 1 week and subsequently switched to the other treatment arm. The primary outcome was the number of real-life STS movements per hour as assessed with a lower back sensor. Secondary outcomes included real-life STS duration, mean/systolic/diastolic blood pressure drop (BPD), orthostatic hypotension questionnaire (OHQ), PD quality of life (PDQ-39), autonomic symptoms (SCOPA-AUT), non-motor symptoms (NMSS), MDS-UPDRS, and activities of daily living (ADL/iADL). RESULTS: Real-life STS frequency on CS was 4.4±4.1 per hour compared with 3.6±2.2 on AB and 3.6±1.8 without treatment (p = 1.0). Concerning the secondary outcomes, NMSS showed significant improvement with CS and AB. OHQ and SCOPA-AUT improved significantly with AB but not CS, and mean BPD drop worsened with CS but not AB. Mean STS duration, PDQ-39, MDS-UPDRS, ADL, and iADL did not significantly change. CONCLUSION: Both AB and CS therapies do not lead to a significant change of physical activity in PD patients with at least moderate symptomatic OH. Secondary results speak for an effect of both therapies concerning non-motor symptoms, with superiority of AB therapy over CS therapy.

[Over 5 years follow-up of three cases of autoimmune autonomic ganglionopathy].

We report the clinical course of three cases of anti-ganglionic acetylcholine receptor (gAChR) antibody positive auto-immune autonomic ganglionopathy (AAG) that have been followed for over 5 years. In all three cases, the symptoms improved by acute treatment, but ultimately relapsed. The first case was a female in her 20s who had a chronic history of photophobia, constipation and amenorrhea. The symptoms almost disappeared by plasma exchange, and menstruation resumed. During the course, it relapsed once after a cold. There was no recurrence of AAG during the two pregnancies. The second case was a male in his 60s who visited a hospital for the acute onset of orthostatic hypotension (OH) and psychological symptoms (infantilization and psychogenic pseudosyncope). Although IVIg was effective, it recurred frequently and was difficult to treat. However, all the symptoms disappeared eight years after the onset without any particular reasons. The third case was a female in her 80s who had a chronic history of OH. Acute treatment was effective, but AAG recurred repeatedly. Additionally, it was difficult to judge relapse because of the residual sequelae. During the course, cerebral hemorrhage due to supine hypertension or short-time blood pressure variability and femoral neck fracture caused by OH occurred. She eventually became a wheelchair. This report is clinically important because there are few reports of long-term follow-up of AAG.

Age and ageing cardiovascular collection: blood pressure, coronary heart disease and heart failure.

As people age they are at increased risk of cardiovascular disease, the leading cause of mortality and morbidity worldwide. Understanding cardiovascular ageing is essential to preserving healthy ageing and preventing serious health outcomes. This collection of papers published in Age and Ageing since 2011 cover key themes in cardiovascular ageing, with a separate collection on stroke and atrial fibrillation planned. Treating high blood pressure remains important as people age and reduces strokes and heart attacks. That said, a more personalised approach to blood pressure may be even more important as people age to lower blood pressure to tight targets where appropriate but avoid overtreatment in vulnerable groups. As people age, more people experience blood pressure drops on standing (orthostatic hypotension), particularly as they become frail. This can predispose them to falls. The papers in this collection provide an insight into blood pressure and orthostatic hypotension. They highlight areas for further research to understand blood pressure changes and management in the ageing population. Inpatient clinical care of older people with heart attacks differs from younger people in UK national audit data. People aged over 80 had improved outcomes in survival after heart attack over time, but had lower rates of specialist input from cardiology compared with younger people. This may partly reflect different clinical presentations, with heart attacks occurring in the context of other health conditions, frailty and multimorbidity. The care and outcomes of acute and chronic cardiovascular disease are impacted by the frailty and health status of an individual at baseline. The research included in this collection reinforces the wide variations in the ageing population and the necessity to focus on the individual needs and priorities, and provide a person-centred multidisciplinary approach to care.

New horizons in the ageing autonomic nervous system: orthostatic hypotension and supine hypertension.

Blood pressure regulation is an automatic, moment-by-moment buffering of the blood pressure in response to physiological changes such as orthostasis, exercise and haemorrhage. This finely orchestrated reflex is called the baroreflex. It is a regulated arc of afferent, central and efferent arms. Multiple physiological changes occur with ageing that can disrupt this reflex, making blood pressure regulation less effective. In addition, multiple changes can occur with ageing-related diseases such as neurodegeneration, atherosclerosis, deconditioning and polypharmacy. These changes commonly result in orthostatic hypotension, hypertension or both, and are consistently associated with multiple adverse outcomes. In this article, we discuss the healthy baroreflex, and physiological and pathophysiological reasons for impaired baroreflex function in older people. We discuss why the common clinical manifestations of orthostatic hypotension and concomitant supine hypertension occur, and strategies for balancing these conflicting priorities. Finally, we discuss strategies for treating them, outlining our practice alongside consensus and expert guidance.

Diagnosis and treatment of orthostatic hypotension.

Orthostatic hypotension is an unusually large decrease in blood pressure on standing that increases the risk of adverse outcomes even when asymptomatic. Improvements in haemodynamic profiling with continuous blood pressure measurements have uncovered four major subtypes: initial orthostatic hypotension, delayed blood pressure recovery, classic orthostatic hypotension, and delayed orthostatic hypotension. Clinical presentations are varied and range from cognitive slowing with hypotensive unawareness or unexplained falls to classic presyncope and syncope. Establishing whether symptoms are due to orthostatic hypotension requires careful history taking, a thorough physical examination, and supine and upright blood pressure measurements. Management and prognosis vary according to the underlying cause, with the main distinction being whether orthostatic hypotension is neurogenic or non-neurogenic. Neurogenic orthostatic hypotension might be the earliest clinical manifestation of Parkinson's disease or related synucleinopathies, and often coincides with supine hypertension. The emerging variety of clinical presentations advocates a stepwise, individualised, and primarily non-pharmacological approach to the management of orthostatic hypotension. Such an approach could include the cessation of blood pressure lowering drugs, adoption of lifestyle measures (eg, counterpressure manoeuvres), and treatment with pharmacological agents in selected cases.

[Intractable Orthostatic Hypotension in Patients with Parkinson's Disease: General Matters about Orthostatic Hypotension and Cautionary Notes through Our Observed Refractory Cases].

Some patients with Parkinson's disease and multiple system atrophy suffer from orthostatic hypotension as a result of cardiovascular autonomic dysfunction. Other complicated dysfunctions, such as spinal hypertension, hinder the management of orthostatic hypotension. A combination of pharmacological and non-pharmacological interventions is required for successful treatment. In this article, I first discuss general matters regarding orthostatic hypotension, after which I describe refractory cases of orthostatic hypotension I have encountered in clinical practice.

[Intractable Orthostatic Hypotension in Patients with Parkinson's Disease: Early Diagnosis and Treatment Strategies].

Orthostatic hypotension (OH) is a common non-motor symptom that occurs in Parkinson's Disease (PD) patients. Typical symptoms of OH are lightheadedness, visual disturbance, and fainting; however, nonspecific symptoms such as dizziness, headache, and fatigue are observed in mild cases. Although OH is prevalent in PD patients, it is often overlooked. Further, after diagnosis, the causative drug should be discontinued and non-pharmacological therapy should be performed,; however, if it is ineffective, additional pharmacological therapy should be administered depending on the symptom severity. The symptoms are usually progressive without proper intervention, and motor functions are affected leading to an increased risk of fainting and falls. Early diagnosis and intervention for OH improves the quality of life and prevents complications in PD patients.

Supine hypertension: A state of the art.

Patients with cardiovascular autonomic failure (AF) may suffer from neurogenic supine hypertension (nSH), defined as systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, after 5 min of rest in the supine position, combined with neurogenic orthostatic hypotension (nOH) in approximately 50% of the cases. nSH may be the manifestation of central or peripheral autonomic lesions. Long-term risks are hypothesized with SH, including renal dysfunction, left ventricular hypertrophy, cerebrovascular disease and cognitive impairment. Yet, large longitudinal studies investigating long-term outcomes of nSH are lacking. In clinical practice, nSH should be investigated in patients with nOH. Office screening should be performed measuring supine BP immediately after lying down and 5 min later, combined with BP measurement on active or passive standing. Home BP recordings performed by patients themselves may also be useful, while 24 h-Ambulatory Blood Pressure Monitoring (ABPM) may allow for detection of nocturnal hypertension and confirm the diagnosis. Current expert recommendations suggest treatment interventions if SBP exceeds 160-180 mmHg. Non-pharmacological strategies represent the first-line treatment approach and include head-up sleeping, avoiding supine position during the daytime, and having a snack before bedtime to lower supine BP using post-prandial hypotension. Pharmacological treatments may be considered if severe nSH persists. Short-acting antihypertensive medications administered at bedtime are preferably used in order to selectively lower supine BP and reduce pressure diuresis without worsening daytime hypotension.