Normal scores of deep breathing tests: beware of dysrhythmia in transthyretin amyloidosis

Wiklund, Urban; Kadkhodaee, Amir; Andersson, Kennet; Suhr, Ole B.; Hörnsten, Rolf

doi:10.1080/13506129.2018.1434140

Cited by 10 publications

(18 citation statements)

References 18 publications

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“…The overall response in heart rate was quantified by the commonly used deep breathing index (DBI), calculated as the average of the heart rate difference in each breathing cycle. DBI was ageadjusted based on linear regression analysis of logarithmically transformed data from controls, from which Z-scores were determined as previously described in [3].…”

Section: Methodsmentioning

confidence: 99%

Vector-Based Analysis of the Similarity Between Breathing and Heart Rate During Paced Deep Breathing

Kleyko

Osipov

Wiklund

2018

2018 Computing in Cardiology Conference (CinC)

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The heart rate (HR) response to paced deep breathing (DB) is a common test of autonomic function, where the scoring is based on indices reflecting the overall heart rate variability (HRV), where high scores are considered as normal findings but can also reflect arrhythmias. This study presents a method based on hyperdimensional computing for assessment of the similarity between feature vectors derived from the HR and breathing signals. The proposed method was used to identify subjects where HR did not follow the paced breathing pattern in recordings from DB tests in 174 healthy subjects and 135 patients with cardiac autonomic neuropathy. Subjects were classified in 4 similarity classes, where the lowest similiarity class included 35 patients and 3 controls. In general, the autonomic function cannot be evaluated in subjects in the lowest similarity class if they also present with high HRV scores, since this combination is a strong indicator of the presence of arrhythmias. Thus, the proposed vector-based similarity analysis is one tool to identify subjects with high HRV but low cardiorespiratory synchronization during the DB test, which falsely can be interpreted as normal autonomic function.

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Section: Methodsmentioning

confidence: 99%

Vector-Based Analysis of the Similarity Between Breathing and Heart Rate During Paced Deep Breathing

Kleyko

Osipov

Wiklund

2018

2018 Computing in Cardiology Conference (CinC)

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“…50 In a study of 165 ATTRm amyloidosis patients carrying the mutation Val30Met, HRV was reduced in 47%. One of the most frequently applied tests is measuring heart rate variability (HRV) in response to deep breathing (six breaths/ min).…”

Section: Autonomic Testingmentioning

confidence: 99%

“…One of the most frequently applied tests is measuring heart rate variability (HRV) in response to deep breathing (six breaths/ min). 50 In a study of 165 ATTRm amyloidosis patients carrying the mutation Val30Met, HRV was reduced in 47%. 50 HRV during physi- However, organs clinically affected and not mentioned above can be also biopsied.…”

Section: Autonomic Testingmentioning

confidence: 99%

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Hereditary transthyretin-related amyloidosis

et al. 2018

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Hereditary transthyretin(TTR)-related amyloidosis (ATTRm amyloidosis) is an endemic/non-endemic, autosomal-dominant, early-and late-onset, rare, progressive disorder, predominantly manifesting as length-dependent, small fiber dominant, axonal polyneuropathy and frequently associated with cardiac disorders and other multisystem diseases. ATTRm amyloidosis is due to variants in the TTR gene, with the substitution Val30Met as the most frequent mutation. TTR mutations lead to destabilization and dissociation of TTR tetramers into variant TTR monomers, and formation of amyloid fibrils, which are consecutively deposited extracellularly in various tissues, such as nerves, heart, brain, eyes, intestines, kidneys, or the skin. Neuropathy may not only include large nerve fibers but also small fibers, and not only sensory and motor fibers but also autonomic fibers. Types of TTR variants, age at onset, penetrance, and clinical presentation vary between geographical areas. Suggestive of a ATTRm amyloidosis are a sensorimotor polyneuropathy, positive family history, autonomic dysfunction, cardiomyopathy, carpal tunnel syndrome, unexplained weight loss, and resistance to immunotherapy. If only sensory A-delta or C fibers are affected, small fiber neuropathy ensues. Diagnostic tests for small fiber neuropathy include determination of intraepidermal nerve fiber density, laser-evoked potentials, heat-and cold-detection thresholds, and measurement of the electrochemical skin conductance. Therapy currently relies on liver transplantation and TTR-stabilizers (tafamidis, diflunisal). K E Y W O R D Samyloid, neuropathy, small fiber, tafamidis, transplantation, transthyretin | 93 FINSTERER ET al. eyes, the gastrointestinal tract, the kidneys, and the skin. ATTRm amyloidosis is resistant to immunotherapy. Though ATTRm-related polyneuropathy or TTR-CA may occur without affection of another tissue, a variable combination of organ affection (multiorgan involvement) is the most frequent phenotype. This review aims at summarizing and discussing previous and recent findings concerning the clinical presentation, genetic background, pathogenesis, diagnosis, treatment, and outcome of ATTRm-related polyneuropathy. | ME THODSData for this review were identified by searches of MEDLINE for references of relevant articles. Search terms applied were "transthyretin," "gene," "TTR-FAP," or "mutation," combined with "neuropathy," "hereditary," "autonomic," "small fiber neuropathy," and "polyneuropathy." Results of the search were screened for potentially relevant studies by application of inclusion and exclusion criteria for the full texts of the relevant studies. Included were randomized controlled trials (RCTs), observational studies with controls, case series, and case reports. Only original articles about humans, and published between 1966 and 2018 were included. Reviews, editorials, and letters were not considered. Reference lists of retrieved studies were checked for reports of additional studies. Websites checked for additional, particularly geneti...

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“…However, this assessment is not always measurable in patients with hATTR amyloidosis (e.g. due to cardiac arrhythmia or electronic pacing) [25,27,50]. To account for this, the measurement of postural hypotension was instead included in the mNIS + 7 Alnylam .…”

Section: Changes From Nis + 7: Autonomic Dysfunctionmentioning

confidence: 99%

Development of measures of polyneuropathy impairment in hATTR amyloidosis: From NIS to mNIS + 7

Dyck

González‐Duarte

Obici

et al. 2019

Journal of the Neurological Sciences

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Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) is a rare, life-threatening disease, caused by point mutations in the transthyretin gene. It is a heterogeneous, multisystem disease with rapidly progressing polyneuropathy (including sensory, motor, and autonomic impairments) and cardiac dysfunction. Measures used to assess polyneuropathy in other diseases have been tested as endpoints in hATTR amyloidosis clinical trials (i.e. Neuropathy Impairment Score [NIS], NIS-lower limb, and NIS + 7), yet the unique nature of the polyneuropathy in this disease has necessitated modifications to these scales. In particular, the heterogeneous impairment and the aggressive disease course have been key drivers in developing scales that better capture the disease burden and progression of polyneuropathy in hATTR amyloidosis. The modified NIS + 7 (mNIS + 7) scale was specifically designed to assess polyneuropathy impairment in patients with hATTR amyloidosis, and has been the primary endpoint in two recent, phase III studies in this disease. The mNIS + 7 uses highly standardized, quantitative, and referenced assessments to quantify decreased muscle weakness, muscle stretch reflexes, sensory loss, and autonomic impairment. Physicians using this scale in clinical trials should be specifically trained and monitored to minimize variability. This article discusses the different scales that have been/are being used to assess polyneuropathy in patients with hATTR amyloidosis, their correlation with other disease assessments, and reflects on how and why scales have evolved to the latest iteration of mNIS + 7. or cardiomyopathy (also known as familial amyloidotic cardiomyopathy); however, it has become apparent that a large majority of patients exhibit signs and symptoms of both polyneuropathy and cardiomyopathy [3,10,11]. The polyneuropathy signs associated with hATTR amyloidosis were first described by Corino de Andrade in 1952, who noted the rapidly progressive nature of this disease [12]. Subsequent research has confirmed that a range of sensory and motor impairments are reported by patients with hATTR amyloidosis with polyneuropathy, the most common of which include neuropathic pain, altered sensation (i.e. decreased pain sensation), numbness, and tingling, along with muscle weakness and impaired balance which lead to difficulty walking [13-15]. The pathologic process typically involves small-fiber damage early in the disease course, often with subsequent damage to peripheral

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Normal scores of deep breathing tests: beware of dysrhythmia in transthyretin amyloidosis

Abstract: Reduced HRV is common in ATTRm amyloidosis patients during DB, however, autonomic function cannot be evaluated in patients presenting with the combination of "normal" scores and low regularity, since their HR responses often reflects dysrhythmias.

Cited by 10 publications

References 18 publications

Vector-Based Analysis of the Similarity Between Breathing and Heart Rate During Paced Deep Breathing

Vector-Based Analysis of the Similarity Between Breathing and Heart Rate During Paced Deep Breathing

Hereditary transthyretin-related amyloidosis

Development of measures of polyneuropathy impairment in hATTR amyloidosis: From NIS to mNIS + 7

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Normal scores of deep breathing tests: beware of dysrhythmia in transthyretin amyloidosis

Abstract: Reduced HRV is common in ATTRm amyloidosis patients during DB, however, autonomic function cannot be evaluated in patients presenting with the combination of "normal" scores and low regularity, since their HR responses often reflects dysrhythmias.

Cited by 10 publications

References 18 publications

Vector-Based Analysis of the Similarity Between Breathing and Heart Rate During Paced Deep Breathing

Vector-Based Analysis of the Similarity Between Breathing and Heart Rate During Paced Deep Breathing

Hereditary transthyretin-related amyloidosis

Development of measures of polyneuropathy impairment in hATTR amyloidosis: From NIS to mNIS + 7

Contact Info

Product

Resources

About

Development of measures of polyneuropathy impairment in hATTR amyloidosis: From NIS to mNIS + 7