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  • Raj, Satish R, et al. (author)
  • Postural orthostatic tachycardia syndrome (POTS) : Priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting - Part 2
  • 2021
  • In: Autonomic Neuroscience: Basic & Clinical. - : Elsevier BV. - 1872-7484. ; 235
  • Journal article (peer-reviewed)abstract
    • The National Institutes of Health hosted a workshop in 2019 to build consensus around the current state of understanding of the pathophysiology of postural orthostatic tachycardia syndrome (POTS) and to identify knowledge gaps that must be addressed to enhance clinical care of POTS patients through research. This second (of two) articles summarizes current knowledge gaps, and outlines the clinical and research priorities for POTS. POTS is a complex, multi-system, chronic disorder of the autonomic nervous system characterized by orthostatic intolerance and orthostatic tachycardia without hypotension. Patients often experience a host of other related disabling symptoms. The functional and economic impacts of this disorder are significant. The pathophysiology remains incompletely understood. Beyond the significant gaps in understanding the disorder itself, there is a paucity of evidence to guide treatment which can contribute to suboptimal care for this patient population. The vast majority of physicians have minimal to no familiarity or training in the assessment and management of POTS. Funding for POTS research remains very low relative to the size of the patient population and impact of the syndrome. In addition to efforts to improve awareness and physician education, an investment in research infrastructure including the development of standardized disease-specific evaluation tools and outcome measures is needed to facilitate effective collaborative research. A national POTS research consortium could facilitate well-controlled multidisciplinary clinical research studies and therapeutic trials. These priorities will require a substantial increase in the number of research investigators and the amount of research funding in this area.
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  • Vernino, Steven, et al. (author)
  • Postural orthostatic tachycardia syndrome (POTS) : State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1
  • 2021
  • In: Autonomic Neuroscience: Basic and Clinical. - : Elsevier BV. - 1566-0702. ; 235
  • Journal article (peer-reviewed)abstract
    • Postural orthostatic tachycardia syndrome (POTS) is a chronic and often disabling disorder characterized by orthostatic intolerance with excessive heart rate increase without hypotension during upright posture. Patients often experience a constellation of other typical symptoms including fatigue, exercise intolerance and gastrointestinal distress. A typical patient with POTS is a female of child-bearing age, who often first displays symptoms in adolescence. The onset of POTS may be precipitated by immunological stressors such as a viral infection. A variety of pathophysiologies are involved in the abnormal postural tachycardia response; however, the pathophysiology of the syndrome is incompletely understood and undoubtedly multifaceted. Clinicians and researchers focused on POTS convened at the National Institutes of Health in July 2019 to discuss the current state of understanding of the pathophysiology of POTS and to identify priorities for POTS research. This article, the first of two articles summarizing the information discussed at this meeting, summarizes the current understanding of this disorder and best practices for clinical care. The evaluation of a patient with suspected POTS should seek to establish the diagnosis, identify co-morbid conditions, and exclude conditions that could cause or mimic the syndrome. Once diagnosed, management typically begins with patient education and non-pharmacologic treatment options. Various medications are often used to address specific symptoms, but there are currently no FDA-approved medications for the treatment of POTS, and evidence for many of the medications used to treat POTS is not robust.
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  • Engstrom, G., et al. (author)
  • Cardiovagal Function Measured by the Deep Breathing Test: Relationships With Coronary Atherosclerosis
  • 2022
  • In: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 11:7
  • Journal article (peer-reviewed)abstract
    • Background The cardiovagal function can be assessed by quantification of respiratory sinus arrhythmia (RSA) during a deep breathing test. However, population studies of RSA and coronary atherosclerosis are lacking. This population-based study examined the relationship between RSA during deep breathing and coronary atherosclerosis, assessed by coronary artery calcium score (CACS). Methods and Results SCAPIS (Swedish Cardiopulmonary Bioimage Study) randomly invited men and women aged 50 to 64 years from the general population. CACS was obtained from computed tomography scanning, and deep breathing tests were performed in 4654 individuals. Expiration-inspiration differences (E-Is) of heart rates were calculated, and reduced RSA was defined as E-I in the lowest decile of the population. The relationship between reduced RSA and CACS (CACS >= 100 or CACS >= 300) was calculated using multivariable-adjusted logistic regression. The proportion of CACS >= 100 was 24% in the lowest decile of E-I and 12% in individuals with E-I above the lowest decile (P<0.001), and the proportion of CACS >= 300 was 12% and 4.8%, respectively (P<0.001). The adjusted odds ratio (OR) for CACS >= 100 was 1.42 (95% CI, 1.10-1.84) and the adjusted OR for CACS >= 300 was 1.62 (95% CI, 1.15-2.28), when comparing the lowest E-I decile with deciles 2 to 10. Adjusted ORs per 1 SD lower E-I were 1.17 (P=0.001) for CACS >= 100 and 1.28 (P=0.001) for CACS >= 300. Conclusions Low RSA during deep breathing is associated with increased coronary atherosclerosis as assessed by CACS, independently of traditional cardiovascular risk factors. Cardiovagal dysfunction could be a prevalent and modifiable risk factor for coronary atherosclerosis in the general population.
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  • Fedorowski, Artur, et al. (author)
  • Antiadrenergic autoimmunity in postural tachycardia syndrome
  • 2017
  • In: Europace. - : Oxford University Press (OUP). - 1099-5129. ; 19:7, s. 1211-1219
  • Journal article (peer-reviewed)abstract
    • Aims Postural tachycardia syndrome (POTS), a common and debilitating cardiovascular disorder, is characterized by an exaggerated heart rate increase during orthostasis and a wide spectrum of adrenergic-related symptoms. To determine the aetiology of POTS, we examined a possible pathophysiological role for autoantibodies against α1-adrenergic (α1AR) and β1/2-adrenergic receptors (β1/2AR). Methods and results Immunoglobulin G (IgG) derived from 17 POTS patients, 7 with recurrent vasovagal syncope (VVS), and 11 normal controls was analysed for its ability to modulate activity and ligand responsiveness of α1AR and β1/2AR in transfected cells and to alter contractility of isolated rat cremaster arterioles in vitro. Immunoglobulin G activation of α1AR and β1/2AR was significantly higher in POTS compared with VVS and controls in cell-based assays. Eight, 11, and 12 of the 17 POTS patients possessed autoantibodies that activated α1AR, β1AR and β2AR, respectively. Pharmacological blockade suppressed IgG-induced activation of α1AR and β1/2AR. Eight of 17 POTS IgG decreased the α1AR responsiveness to phenylephrine and 13 of 17 POTS IgG increased the β1AR responsiveness to isoproterenol irrespective of their ability to directly activate their receptors. Postural tachycardia syndrome IgG contracted rat cremaster arterioles, which was reversed by α1AR blockade. The upright heart rate correlated with IgG-mediated β1AR and α1AR activity but not with β2AR activity. Conclusion These data confirm a strong relationship between adrenergic autoantibodies and POTS. They support the concept that allosteric-mediated shifts in the α1AR and β1AR responsiveness are important in the pathophysiology of postural tachycardia.
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  • Sutton, R, et al. (author)
  • Artur Pietrucha (1964-2020)
  • 2021
  • In: Kardiologia polska. - 1897-4279. ; 79:6, s. 720-721
  • Journal article (peer-reviewed)
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  • Bachus, E, et al. (author)
  • Monitoring of cerebral oximetry during head-up tilt test in adults with history of syncope and orthostatic intolerance
  • 2018
  • In: Europace. - : Oxford University Press (OUP). - 1532-2092.
  • Journal article (peer-reviewed)abstract
    • Aims: We applied near-infrared-spectroscopy (NIRS) to measure absolute frontal cerebral tissue oxygen saturation (SctO2) during head-up tilt test (HUT) in patients investigated for unexplained syncope.Methods and results: Synchronized non-invasive beat-to-beat haemodynamic monitoring, ECG, SctO2 (NIRS; normal range: 60-80%), and peripheral oxygen saturation (left hand, SpO2) were applied during HUT in a random sample of patients with unexplained syncope. Tracings of 54 patients (mean-age: 55 ± 19 years, 39% male) with negative HUT, vasovagal syncope (VVS), or orthostatic hypotension (OH) were analysed. In 44 patients HUT was diagnostic, in 10 HUT was negative. Thirty-one experienced VVS. Of these, 6 had spontaneous and 25 nitroglycerin-induced syncope. Thirteen patients had orthostatic hypotension (OH). Although there was no significant change in mean-arterial pressure from baseline to 1 min before syncope or end of passive HUT phase (-1.4 ± 13.9 mmHg; P = 0.45), there was a significant fall in SctO2 during the same period (-3.2 ± 3.2%; P ≤ 0.001). Among patients who experienced syncope, a decrease in SctO2 from 71 ± 5% at baseline to 53 ± 9% (P < 0.001) at syncope was observed. During HUT, there was a significant difference in delta SctO2 between spontaneous VVS (-4.5 ± 3.0%) and negative HUT (-1.3 ± 1.9%; P = 0.021), but not between spontaneous VVS and OH (-5.4 ± 4.2%; P = 0.65). In spontaneous VVS, progressive decrease of SctO2 was independent of mean arterial pressure decrease (P = 0.22).Conclusions: Progressive decrease in cerebral tissue oxygenation independent of mean-arterial pressure may precede spontaneous vasovagal reflex during tilt. Patients experience syncope when SctO2 falls below 60%. These data confirm clinical utility of absolute cerebral oximetry monitoring for syncope investigation. We applied NIRS to measure frontal cerebral tissue oxygen saturation (SctO2) during head-up tilt test (HUT) in patients with unexplained syncope. In 44 of 54 patients, HUT was diagnostic. In patients with syncope, a significant SctO2-decrease was observed. Different patterns of SctO2 can be detected.
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  • Bisaccia, Giandomenico, et al. (author)
  • Post-Acute Sequelae of COVID-19 and Cardiovascular Autonomic Dysfunction : What Do We Know?
  • 2021
  • In: Journal of cardiovascular development and disease. - : MDPI AG. - 2308-3425. ; 8:11, s. 1-15
  • Research review (peer-reviewed)abstract
    • Post-acute sequelae of SARS-CoV-2 (PASC), or long COVID syndrome, is emerging as a major health issue in patients with previous SARS-CoV-2 infection. Symptoms commonly experienced by patients include fatigue, palpitations, chest pain, dyspnea, reduced exercise tolerance, and "brain fog". Additionally, symptoms of orthostatic intolerance and syncope suggest the involvement of the autonomic nervous system. Signs of cardiovascular autonomic dysfunction appear to be common in PASC and are similar to those observed in postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. In this review, we report on the epidemiology of PASC, discuss current evidence and possible mechanisms underpinning the dysregulation of the autonomic nervous system, and suggest nonpharmacological and pharmacological interventions to treat and relieve symptoms of PASC-associated dysautonomia.
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  • Brignole, Michele, et al. (author)
  • Low-blood pressure phenotype underpins the tendency to reflex syncope
  • 2021
  • In: Journal of Hypertension. - 1473-5598. ; 39:7, s. 1319-1325
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: We hypothesized that cardiovascular physiology differs in reflex syncope patients compared with the general population, predisposing such individuals to vasovagal reflex.METHODS: In this multicohort cross-sectional study, we compared aggregate data of resting SBP, DBP, pulse pressure (PP) and heart rate (HR), collected from six community-based cohort studies (64 968 observations) with those from six databases of reflex syncope patients (6516 observations), subdivided by age decades and sex.RESULTS: Overall, in male individuals with reflex syncope, SBP (-3.4 mmHg) and PP (-9.2 mmHg) were lower and DBP (+2.8 mmHg) and HR (+5.1 bpm) were higher than in the general population; the difference in SBP was higher at ages above 60 years. In female individuals, PP (-6.0 mmHg) was lower and DBP (+4.7 mmHg) and HR (+4.5 bpm) were higher than in the general population; differences in SBP were less pronounced, becoming evident only above 60 years. Compared with male individuals, SBP in female individuals exhibited slower increase until age 40 years, and then demonstrated steeper increase that continued throughout remaining life.CONCLUSION: The patients prone to reflex syncope demonstrate a different resting cardiovascular haemodynamic profile as compared with a general population, characterized by lower SBP and PP, reflecting reduced venous return and lower stroke volume, and a higher HR and DBP, suggesting the activation of compensatory mechanisms. Our data contribute to a better understanding why some individuals with similar demographic characteristics develop reflex syncope and others do not.VIDEO ABSTRACT: http://links.lww.com/HJH/B580.
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  • Brignole, M, et al. (author)
  • Mechanism-based therapy of non-cardiac syncope: a practical guide
  • 2024
  • In: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. - 1532-2092. ; 26:4
  • Journal article (peer-reviewed)
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  • Fedorowski, Artur, et al. (author)
  • Cardiovascular autonomic dysfunction in post-COVID-19 syndrome : a major health-care burden
  • 2024
  • In: Nature Reviews Cardiology. - 1759-5002. ; 21:6, s. 361-378
  • Research review (peer-reviewed)abstract
    • Cardiovascular autonomic dysfunction (CVAD) is a malfunction of the cardiovascular system caused by deranged autonomic control of circulatory homeostasis. CVAD is an important component of post-COVID-19 syndrome, also termed long COVID, and might affect one-third of highly symptomatic patients with COVID-19. The effects of CVAD can be seen at both the whole-body level, with impairment of heart rate and blood pressure control, and in specific body regions, typically manifesting as microvascular dysfunction. Many severely affected patients with long COVID meet the diagnostic criteria for two common presentations of CVAD: postural orthostatic tachycardia syndrome and inappropriate sinus tachycardia. CVAD can also manifest as disorders associated with hypotension, such as orthostatic or postprandial hypotension, and recurrent reflex syncope. Advances in research, accelerated by the COVID-19 pandemic, have identified new potential pathophysiological mechanisms, diagnostic methods and therapeutic targets in CVAD. For clinicians who daily see patients with CVAD, knowledge of its symptomatology, detection and appropriate management is more important than ever. In this Review, we define CVAD and its major forms that are encountered in post-COVID-19 syndrome, describe possible CVAD aetiologies, and discuss how CVAD, as a component of post-COVID-19 syndrome, can be diagnosed and managed. Moreover, we outline directions for future research to discover more efficient ways to cope with this prevalent and long-lasting condition.
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  • Fedorowski, Artur, et al. (author)
  • Orthostatic Hypotension : Management of a Complex, But Common, Medical Problem
  • 2022
  • In: Circulation: Arrhythmia and Electrophysiology. - 1941-3084. ; 15:3
  • Journal article (peer-reviewed)abstract
    • Orthostatic hypotension (OH), a common, often overlooked, disorder with many causes, is associated with debilitating symptoms, falls, syncope, cognitive impairment, and risk of death. Chronic OH, a cardinal sign of autonomic dysfunction, increases with advancing age and is commonly associated with neurodegenerative and autoimmune diseases, diabetes, hypertension, heart failure, and kidney failure. Management typically involves a multidisciplinary, patient-centered, approach to arrive at an appropriate underlying diagnosis that is causing OH, treating accompanying conditions, and providing individually tailored pharmacological and nonpharmacological treatment. We (1) propose a novel streamlined pathophysiological classification of OH; (2) review the relationship between the cardiovascular disease continuum and OH; (3) discuss OH-mediated end-organ damage; (4) provide diagnostic and therapeutic algorithms to guide clinical decision making and patient care; (5) identify current gaps in knowledge and try to define future research directions. Using a case-based learning approach, specific clinical scenarios are presented highlighting various presentations of OH to provide a practical guide to evaluate and manage patients who have OH.
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  • Fedorowski, Artur, et al. (author)
  • Other syndromes of orthostatic intolerance : Delayed orthostatic hypotension, postprandial hypotension, postural orthostatic tachycardia syndrome, and reflex syncope
  • 2021
  • In: Orthostatic Hypotension in Older Adults. - Cham : Springer International Publishing. - 9783030624934 - 9783030624927 ; , s. 121-143
  • Book chapter (peer-reviewed)abstract
    • Apart from classical orthostatic hypotension, the gravitational force may strongly contribute to other forms of orthostatic intolerance, delayed and postprandial OH, postural orthostatic tachycardia syndrome (POTS), and reflex syncope. In delayed OH, the significant blood pressure drop occurs first after 3-min period of orthostasis, whereas in postprandial OH, the symptoms appear first approximately 15-30 min after the meal. POTS is rarely seen in older adults and presents as abnormal sinus tachycardia on standing with symptoms of orthostatic intolerance, dizziness, fatigue, and cognitive impairment. Reflex syncope may manifest as orthostatic vasovagal reflex, situational syncope, or carotid sinus hypersensitivity, which becomes a clinical syndrome when associated with history of unexplained syncope and positive provocation test, carotid sinus massage. Older patients with a history of orthostatic intolerance, unexplained syncope and fall trauma, and negative result of active standing test should be further evaluated using cardiovascular autonomic tests such as head-up tilt testing, Valsalva maneuver, and carotid sinus massage.
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  • Fedorowski, A. (author)
  • Postural orthostatic tachycardia syndrome : clinical presentation, aetiology and management
  • 2019
  • In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 285:4, s. 352-366
  • Journal article (peer-reviewed)abstract
    • Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular autonomic disorder characterized by an excessive heart rate increase on standing and orthostatic intolerance. POTS affects younger individuals 15–45 years old with a distinct female predominance (≈80%). The prevalence ranges between 0.2% and 1.0% in developed countries. The onset of POTS is typically precipitated by immunological stressors such as viral infection, vaccination, trauma, pregnancy, surgery or psychosocial stress. The most common complaints are dizziness, weakness, rapid heartbeat and palpitation on standing. Moreover, patients often report physical deconditioning and reduced exercise capacity as well as headache, ‘brain fog’, dyspnoea, gastrointestinal disorders and musculoskeletal pain. The aetiology of POTS is largely unknown and three main hypotheses include an autoimmune disorder, abnormally increased sympathetic activity and catecholamine excess, and sympathetic denervation leading to central hypovolaemia and reflex tachycardia. The golden standard for POTS diagnosis is head-up tilt test with a non-invasive beat-to-beat haemodynamic monitoring. Although long-term prognosis of POTS is poorly explored, around 50% of patients spontaneously recover within 1–3 years. After the diagnosis has been established, patient should be thoroughly educated about non-pharmacological measures alleviating the symptoms. Exercise training may be very effective and counteract deconditioning. In more symptomatic patients, different drugs directed at controlling heart rate, increasing peripheral vasoconstriction and intravascular volume can be tested. However, the overall effects of pharmacological therapy are modest and the most affected patients remain handicapped. Future efforts should focus on better understanding of POTS pathophysiology and designing randomized controlled trials for selection of more effective therapy.
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  • Finucane, Ciarán, et al. (author)
  • A practical guide to active stand testing and analysis using continuous beat-to-beat non-invasive blood pressure monitoring
  • 2019
  • In: Clinical Autonomic Research. - : Springer Science and Business Media LLC. - 0959-9851 .- 1619-1560. ; 29:4, s. 427-441
  • Research review (peer-reviewed)abstract
    • Purpose: The average adult stands approximately 50–60 times per day. Cardiovascular responses evoked during the first 3 min of active standing provide a simple means to clinically assess short-term neural and cardiovascular function across the lifespan. Clinically, this response is used to identify the haemodynamic correlates of patient symptoms and attributable causes of (pre-)syncope, and to detect autonomic dysfunction, variants of orthostatic hypotension, postural orthostatic tachycardia syndrome and orthostatic hypertension. Methods: This paper provides a set of experience/expertise-based recommendations detailing current state-of-the-art measurement and analysis approaches for the active stand test, focusing on beat-to-beat BP technologies. This information is targeted at those interested in performing and interpreting the active stand test to current international standards. Results: This paper presents a practical step-by-step guide on (1) how to perform active stand measurements using beat-to-beat continuous blood pressure measurement technologies, (2) how to conduct an analysis of the active stand response and (3) how to identify the spectrum of abnormal blood pressure and heart rate responses which are of clinical interest. Conclusion: Impairments in neurocardiovascular control are an attributable cause of falls and syncope across the lifespan. The simple active stand test provides the clinician with a powerful tool for assessing individuals at risk of such common disorders. However, its simplicity belies the complexity of its interpretation. Care must therefore be taken in administering and interpreting the test in order to maximise its clinical benefit and minimise its misinterpretation.
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  • Holm, H, et al. (author)
  • Beta-blocker therapy and risk of vascular dementia: A population-based prospective study
  • 2020
  • In: Vascular pharmacology. - : ELSEVIER SCIENCE INC. - 1537-1891 .- 1879-3649. ; 125
  • Journal article (peer-reviewed)abstract
    • There are a few studies that report cognitive impairment as a complication of treatment with beta-blockers. We aimed to evaluate the longitudinal association between use of beta-blockers, as a class, and incident risk of all-cause dementia, vascular dementia, Alzheimers and mixed dementia in the prospective population-based Malmo Preventive Project. We included 18,063 individuals (mean age 68.2, males 63.4%) followed up for 84,506 person-years. Dementia cases were retrieved from the Swedish National Patient Register and validated by review of medical records and neuroimaging data. We performed propensity score matching analysis, resulting in 3720 matched pairs of beta-blocker users and non-users at baseline, and multivariable Cox proportional-hazards regression. Overall, 122 study participants (1.6%) were diagnosed with dementia during the follow-up. Beta-blocker therapy was independently associated with increased risk of developing vascular dementia, regardless of confounding factors (HR: 1.72, 95%CI 1.01-3.78; p = .048). Conversely, treatment with beta-blockers was not associated with increased risk of all-cause, Alzheimers and mixed dementia (HR:1.15; 95%CI 0.80-1.66; p = .44; HR:0.85; 95%CI 0.48-1.54; P = .59 and HR:1.35; 95%CI 0.56-3.27; p = .50, respectively). We observed that use of beta-blockers, as a class, is associated with increased longitudinal risk of vascular dementia in the general elderly population, regardless of cardiovascular risk factors, prevalent or incident history of atrial fibrillation, stroke, coronary events and heart failure. Further studies are needed to confirm our findings in the general population and to explore the mechanisms underlying the relationship between use of beta-blockers and increased risk of vascular dementia.
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  • Holm, Hannes, et al. (author)
  • Biomarkers of microvascular endothelial dysfunction predict incident dementia : a population-based prospective study
  • 2017
  • In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 282:1, s. 94-101
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Cerebral endothelial dysfunction occurs in a spectrum of neurodegenerative diseases. Whether biomarkers of microvascular endothelial dysfunction can predict dementia is largely unknown. We explored the longitudinal association of midregional pro-atrial natriuretic peptide (MR-proANP), C-terminal endothelin-1 (CT-proET-1) and midregional proadrenomedullin (MR-proADM) with dementia and subtypes amongst community-dwelling older adults.METHODS: A population-based cohort of 5347 individuals (men, 70%; age, 69 ± 6 years) without prevalent dementia provided plasma for determination of MR-proANP, CT-proET-1 and MR-proADM. Three-hundred-and-seventy-three patients (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) over a period of 4.6 ± 1.3 years. Relations between baseline biomarker plasma concentrations and incident dementia were assessed using multivariable Cox regression analysis.RESULTS: Higher levels of MR-proANP were significantly associated with increased risk of all-cause and vascular dementia (hazard ratio [HR] per 1 SD: 1.20, 95% confidence interval [CI], 1.07-1.36; P = 0.002, and 1.52; 1.21-1.89; P < 0.001, respectively). Risk of all-cause dementia increased across the quartiles of MR-proANP (p for linear trend = 0.004; Q4, 145-1681 pmol L(-1) vs. Q1, 22-77 pmol L(-1) : HR: 1.83; 95%CI: 1.23-2.71) and was most pronounced for vascular type (p for linear trend = 0.005: HR: 2.71; 95%CI: 1.14-6.46). Moreover, the two highest quartiles of CT-proET-1 predicted vascular dementia with a cut-off value at 68 pmol L(-1) (Q3-Q4, 68-432 pmol L(-1) vs. Q1-Q2,4-68 pmol L(-1) ; HR: 1.94; 95%CI: 1.12-3.36). Elevated levels of MR-proADM indicated no increased risk of developing dementia after adjustment for traditional risk factors.CONCLUSIONS: Elevated plasma concentration of MR-proANP is an independent predictor of all-cause and vascular dementia. Pronounced increase in CT-proET-1 indicates higher risk of vascular dementia.
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30.
  • Holm, H, et al. (author)
  • High circulating levels of midregional proenkephalin A predict vascular dementia : a population-based prospective study
  • 2020
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
  • Journal article (peer-reviewed)abstract
    • Midregional Pro-enkephalin A (MR-PENK A) and N-terminal Protachykinin A (NT-PTA) have been associated with vascular dementia. However, the longitudinal relationship between these biomarkers and incident dementia has not been fully investigated. In the population-based Malmö Preventive Project, circulating levels of MR-PENK A and NT-PTA were determined in a random sample of 5,323 study participants (mean age: 69 ± 6 years) who were followed-up over a period of 4.6 ± 1.6 years. The study sample included 369 patients (7%) who were diagnosed in the same period with dementia. We analyzed relationship of MR-PENK A and NT-PTA with the risk of developing dementia by using multivariable-adjusted Cox regression models adjusted for traditional risk factors. Increased plasma levels of MR-PENK A were associated with higher risk of incident vascular dementia whereas no associations were found with all-cause or Alzheimer dementia. The risk of vascular dementia was mainly conferred by the highest quartile of MR-PENK as compared with lower quartiles. Elevated levels of NT-PTA yielded significant association with all-cause dementia or dementia subtypes. Elevated plasma concentration of MR-PENK A independently predicts vascular dementia in the general population. MR-PENK A may be used as an additional tool for identifying vascular subtype in ambiguous dementia cases.
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  • Ricci, Fabrizio, et al. (author)
  • Pulmonary blood volume index as a quantitative biomarker of haemodynamic congestion in hypertrophic cardiomyopathy
  • 2019
  • In: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2412 .- 2047-2404. ; 20:12, s. 1368-1376
  • Journal article (peer-reviewed)abstract
    • AIMS : The non-invasive assessment of left ventricular (LV) diastolic function and filling pressure in hypertrophic cardiomyopathy (HCM) is still an open issue. Pulmonary blood volume index (PBVI) by cardiovascular magnetic resonance (CMR) has been proposed as a quantitative biomarker of haemodynamic congestion. We aimed to assess the diagnostic accuracy of PBVI for left atrial pressure (LAP) estimation in patients with HCM. METHODS AND RESULTS : We retrospectively identified 69 consecutive HCM outpatients (age 58 ± 11 years; 83% men) who underwent both transthoracic echocardiography (TTE) and CMR. Guideline-based detection of LV diastolic dysfunction was assessed by TTE, blinded to CMR results. PBVI was calculated as the product of right ventricular stroke volume index and the number of cardiac cycles for a bolus of gadolinium to pass through the pulmonary circulation as assessed by first-pass perfusion imaging. Compared to patients with normal LAP, patients with increased LAP showed significantly larger PBVI (463 ± 127 vs. 310 ± 86 mL/m2, P < 0.001). PBVI increased progressively with worsening New York Heart Association functional class and echocardiographic stages of diastolic dysfunction (P < 0.001 for both). At the best cut-off point of 413 mL/m2, PBVI yielded good diagnostic accuracy for the diagnosis of LV diastolic dysfunction with increased LAP [C-statistic = 0.83; 95% confidence interval (CI): 0.73-0.94]. At multivariable logistic regression analysis, PBVI was an independent predictor of increased LAP (odds ratio per 10% increase: 1.97, 95% CI: 1.06-3.68; P = 0.03). CONCLUSION : PBVI is a promising CMR application for assessment of diastolic function and LAP in patients with HCM and may serve as a quantitative marker for detection, grading, and monitoring of haemodynamic congestion.
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38.
  • Thijs, RD, et al. (author)
  • How to unblur the vasovagal evidence?
  • 2023
  • In: Clinical autonomic research : official journal of the Clinical Autonomic Research Society. - : Springer Science and Business Media LLC. - 1619-1560. ; 33:1, s. 5-7
  • Journal article (other academic/artistic)
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39.
  • van den Berg, Victor J, et al. (author)
  • IgM anti-malondialdehyde low density lipoprotein antibody levels indicate coronary heart disease and necrotic core characteristics in the Nordic Diltiazem (NORDIL) study and the Integrated Imaging and Biomarker Study 3 (IBIS-3)
  • 2018
  • In: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 36, s. 63-72
  • Journal article (peer-reviewed)abstract
    • Background: Certain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis.Objectives: We tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics.Methods: NORDIL was a prospective study investigating adverse cardiovascular outcomes in hypertensive patients. IBIS-3 analyzed lesions in a non-culprit coronary artery with <50% stenosis using radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS). Imaging was repeated after a median of 386?days on rosuvastatin. Associations of antibodies with incident CHD and imaging parameters were assessed in the two sub-studies respectively.Findings: From 10,881 NORDIL patients, 87 had serum sampled at baseline and developed CHD over 4.5 years, matched to 227 controls. Higher titers of IgM anti-MDA-LDL had a protective effect on adverse outcomes, with odds ratio 0.29 (0.11, 0.76; p=0.012; p=0.016 for trend). Therefore, the effect was explored at the lesional level in IBIS-3. 143 patients had blood samples and RF-IVUS measurements available, and NIRS was performed in 90 of these. At baseline, IgM anti-MDA-LDL levels had a strong independent inverse relationship with lesional necrotic core volume (p=0.027) and percentage of plaque occupied by necrotic core (p=0.011), as well as lipid core burden index (p=0.024) in the worst 4 mm segment.Interpretation: Our study supports the hypothesis that lower circulating levels of IgM anti-MDA-LDL are associated with clinical CHD development, and for the first time relates these findings to atherosclerotic plaque characteristics that are linked to vulnerability.
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40.
  • Vandermolen, Sebastian, et al. (author)
  • 'The digital cardiologist' : How technology is changing the paradigm of cardiology training
  • 2022
  • In: Current Problems in Cardiology. - : Elsevier BV. - 0146-2806 .- 1535-6280. ; 47:12
  • Research review (peer-reviewed)abstract
    • In the same way that the practice of cardiology has evolved over the years, so too has the way cardiology fellows in training (FITs) are trained. Propelled by recent advances in technology-catalysed by COVID-19-and the requirement to adapt age-old methods of both teaching and healthcare delivery, many aspects, or 'domains', of learning have changed. These include the environments in which FITs work (outpatient clinics, 'on-call' inpatient service) and procedures in which they need clinical competency. Further advances in virtual reality are also changing the way FITs learn and interact. The proliferation of technology into the cardiology curriculum has led to some describing the need for FITs to develop into 'digital cardiologists', namely those who comfortably use digital tools to aid clinical practice, teaching, and training whilst, at the same time, retain the ability for human analysis and nuanced assessment so important to patient-centred training and clinical care.
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41.
  • Yu, Xichun, et al. (author)
  • Angiotensin II type 1 receptor autoantibodies in postural tachycardia syndrome
  • 2018
  • In: Journal of the American Heart Association. - 2047-9980. ; 7:8
  • Journal article (peer-reviewed)abstract
    • Background--Both the adrenergic and renin-angiotensin systems contribute to orthostatic circulatory homeostasis, which is impaired in postural orthostatic tachycardia syndrome (POTS). Activating autoantibodies to the α1-adrenergic and β1/2-adrenergic receptors have previously been found in sera from patients with POTS. We hypothesized that patients with POTS might also harbor activating autoantibodies to the angiotensin II type 1 receptor (AT1R) independently of antiadrenergic autoimmunity. This study examines a possible pathophysiological role for AT1R autoantibodies in POTS. Methods and Results--Serum immunoglobulin G from 17 patients with POTS, 6 patients with recurrent vasovagal syncope, and 10 normal controls was analyzed for the ability to activate AT1R and alter AT1R ligand responsiveness in transfected cells in vitro. Of 17 subjects with POTS, 12 demonstrated significant AT1R antibody activity in immunoglobulin G purified from their serum. No significant AT1R antibody activity was found in the subjects with vasovagal syncope or healthy subjects. AT1R activation by POTS immunoglobulin G was specifically blocked by the AT1R blocker losartan. Moreover, POTS immunoglobulin G significantly shifted the angiotensin II dosage response curve to the right, consistent with an inhibitory effect. All subjects with POTS were positive for one or both autoantibodies to the AT1R and α1-adrenergic receptor. Conclusions--Most patients with POTS harbor AT1R antibody activity. This supports the concept that AT1R autoantibodies and antiadrenergic autoantibodies, acting separately or together, may exert a significant impact on the cardiovascular pathophysiological characteristics in POTS.
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