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      Analysis of Heart-Rate Variability during Angioedema Attacks in Patients with Hereditary C1-Inhibitor Deficiency

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          Abstract

          C1-inhibitor hereditary angioedema (C1-INH-HAE) is a rare disease characterized by self-limiting edema associated with localized vasodilation due to increased levels of circulating bradykinin. C1-INH-HAE directly influences patients’ everyday lives, as attacks are unpredictable in frequency, severity, and the involved anatomical site. The autonomic nervous system could be involved in remission. The cardiac autonomic profile has not yet been evaluated during the attack or prodromal phases. In this study, a multiday continuous electrocardiogram was obtained in four C1-INH-HAE patients until attack occurrence. Power spectral heart rate variability (HRV) indices were computed over the 4 h preceding the attack and during the first 4 h of the attack in three patients. Increased vagal modulation of the sinus node was detected in the prodromal phase. This finding may reflect localized vasodilation mediated by the release of bradykinin. HRV analysis may furnish early markers of an impending angioedema attack, thereby helping to identify patients at higher risk of attack recurrence. In this perspective, it could assist in the timing, titration, and optimization of prophylactic therapy, and thus improve patients’ quality of life.

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          Most cited references28

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          Heart rate variability: Standards of measurement, physiological interpretation, and clinical use

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            Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog.

            In 57 normal subjects (age 20-60 years), we analyzed the spontaneous beat-to-beat oscillation in R-R interval during control recumbent position, 90 degrees upright tilt, controlled respiration (n = 16) and acute (n = 10) and chronic (n = 12) beta-adrenergic receptor blockade. Automatic computer analysis provided the autoregressive power spectral density, as well as the number and relative power of the individual components. The power spectral density of R-R interval variability contained two major components in power, a high frequency at approximately 0.25 Hz and a low frequency at approximately 0.1 Hz, with a normalized low frequency:high frequency ratio of 3.6 +/- 0.7. With tilt, the low-frequency component became largely predominant (90 +/- 1%) with a low frequency:high frequency ratio of 21 +/- 4. Acute beta-adrenergic receptor blockade (0.2 mg/kg IV propranolol) increased variance at rest and markedly blunted the increase in low frequency and low frequency:high frequency ratio induced by tilt. Chronic beta-adrenergic receptor blockade (0.6 mg/kg p.o. propranolol, t.i.d.), in addition, reduced low frequency and increased high frequency at rest, while limiting the low frequency:high frequency ratio increase produced by tilt. Controlled respiration produced at rest a marked increase in the high-frequency component, with a reduction of the low-frequency component and of the low frequency:high frequency ratio (0.7 +/- 0.1); during tilt, the increase in the low frequency:high frequency ratio (8.3 +/- 1.6) was significantly smaller. In seven additional subjects in whom direct high-fidelity arterial pressure was recorded, simultaneous R-R interval and arterial pressure variabilities were examined at rest and during tilt. Also, the power spectral density of arterial pressure variability contained two major components, with a relative low frequency:high frequency ratio at rest of 2.8 +/- 0.7, which became 17 +/- 5 with tilt. These power spectral density components were numerically similar to those observed in R-R variability. Thus, invasive and noninvasive studies provided similar results. More direct information on the role of cardiac sympathetic nerves on R-R and arterial pressure variabilities was derived from a group of experiments in conscious dogs before and after bilateral stellectomy. Under control conditions, high frequency was predominant and low frequency was very small or absent, owing to a predominant vagal tone. During a 9% decrease in arterial pressure obtained with IV nitroglycerin, there was a marked increase in low frequency, as a result of reflex sympathetic activation.(ABSTRACT TRUNCATED AT 400 WORDS)
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              Assessment of autonomic function in humans by heart rate spectral analysis

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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Environ Res Public Health
                Int J Environ Res Public Health
                ijerph
                International Journal of Environmental Research and Public Health
                MDPI
                1661-7827
                1660-4601
                12 March 2021
                March 2021
                : 18
                : 6
                : 2900
                Affiliations
                [1 ]Department of Medicine, IRCCS Istituti Clinici Scientifici Maugeri, 20138 Milan, Italy; azzurra.cesoni@ 123456icsmaugeri.it (A.M.C.); valeria.degrazia@ 123456icsmaugeri.it (V.D.G.); lorenza.zingale@ 123456icsmaugeri.it (L.C.Z.); laura.dallavecchia@ 123456icsmaugeri.it (L.A.D.V.)
                [2 ]Bioengineering Laboratory, IRCCS Istituti Clinici Scientifici Maugeri, 20138 Milan, Italy; beatrice.demaria@ 123456icsmaugeri.it
                [3 ]Department of Translational Medical Sciences and Center for Basic and Clinical Immunology Research (CISI), University of Naples “Federico II”, 80138 Naples, Italy; bovamaria@ 123456virgilio.it (M.B.); petrarol@ 123456unina.it (A.P.); spadaro@ 123456unina.it (G.S.)
                [4 ]Department of Biomedical Sciences for Health, University of Milan, 20133 Milan, Italy; alberto.porta@ 123456unimi.it
                [5 ]Department of Cardiothoracic, Vascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, San Donato Milanese, 20097 Milan, Italy
                Author notes
                Author information
                https://orcid.org/0000-0003-3973-6931
                https://orcid.org/0000-0001-5360-3137
                https://orcid.org/0000-0002-7655-0696
                https://orcid.org/0000-0001-5700-7164
                https://orcid.org/0000-0002-6720-9824
                https://orcid.org/0000-0002-6516-0959
                Article
                ijerph-18-02900
                10.3390/ijerph18062900
                8002127
                33809031
                ae3e2589-fbb0-4890-a653-13b9c2e97557
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 10 February 2021
                : 09 March 2021
                Categories
                Article

                Public health
                c1-inhibitor hereditary angioedema,heart rate variability,cardiac neural control,autonomic nervous system,spectral analysis,multiday ecg monitoring,quality of life,burden of disease

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