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  • 1.
    Alenius Dahlqvist, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Karlsson, Marcus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Handheld ECG in analysis of arrhythmia and heart rate variability in children with Fontan circulation2014In: Journal of Electrocardiology, ISSN 0022-0736, E-ISSN 1532-8430, Vol. 47, no 3, p. 374-382Article in journal (Refereed)
    Abstract [en]

    Background: Our aim was to evaluate the intermittent use of a handheld ECG system for detecting silent arrhythmias and cardiac autonomic dysfunction in children with univentricular hearts. Methods: Twenty-seven patients performed intermittent ECG recordings with handheld devices during a 14-day period. A manual arrhythmia analysis was performed. We analyzed heart rate variability (HRV) using scatter plots of all interbeat intervals (Poincare plots) from the total observation period. Reference values of HRV indices were determined from Holter-ECGs in 41 healthy children. Results: One asymptomatic patient had frequent ventricular extra systoles. Another patient had episodes with supraventricular tachycardia (with concomitant palpitations). Seven patients showed reduced HRV. Conclusions: Asymptomatic arrhythmia was detected in one patient. The proposed method for pooling of intermittent recordings from handheld or similar devices may be used for detection of arrhythmias as well as for cardiac autonomic dysfunction.

  • 2.
    Alenius Dahlqvist, Jenny
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Karlsson, Marcus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Strömvall-Larsson, Eva
    Division of Cardiology, Department of Paediatrics, Sahlgrenska University Hospital/Queen Silvia Children’s Hospital, Göteborg University, Göteborg, Sweden.
    Berggren, Håkan
    Division of Cardiothoracic Surgery, Department of Paediatrics, Sahlgrenska University Hospital/Queen Silvia Children’s Hospital, Göteborg University, Göteborg, Sweden.
    Hanseus, Katarina
    Department of Paediatrics, Children’s Hospital, Lund University Hospital, Lund, Sweden.
    Johansson, Sune
    Paediatric Cardiac Surgical Unit, Children’s Hospital, Lund University Hospital, Lund, Sweden.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Heart rate variability in children with fontan circulation: lateral tunnel and extracardiac conduit2012In: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 33, no 2, p. 307-315Article in journal (Refereed)
    Abstract [en]

    The technique in Fontan surgery has developed from the lateral tunnel (LT) toward the extracardiac conduit (EC) used to reduce long-term complications such as atrial arrhythmia and sinus node dysfunction. Heart rate variability (HRV) examines cardiac nervous activity controlling the sinus node. This study aimed to investigate HRV in a cohort of children with univentricular hearts, focusing on the relation between HRV and surgical procedure. For 112 children with Fontan circulation, HRV was analyzed using power spectral analysis. Spectral power was determined in three regions: very-low-frequency (VLF), low-frequency (LF), and high-frequency (HF) regions. Patients were compared with 66 healthy controls subject. Patients with LT were compared with patients who had EC. The children with Fontan circulation showed a significantly reduced HRV including total power (P < 0.0001), VLF (P < 0.0001), LF (P < 0.0001), and HF (P = 0.001) compared with the control subjects. The LT and EC patients did not differ significantly. Reduced HRV was found in both the LT and EC patients. In terms of HRV reduction, EC was not superior to LT.

  • 3.
    Heldestad, Victoria
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Obayashi, Konen
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nordh, Erik
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Comparison of quantitative sensory testing and heart rate variability in Swedish Val30Met ATTR2011In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 18, no 4, p. 183-190Article in journal (Refereed)
    Abstract [en]

    Patients with transthyretin amyloidosis (ATTR) polyneuropathy, a hereditary fatal disease, often report defects in both thermal perception and autonomic nervous system function as their first clinical symptoms. While elevated thermal perception thresholds (TPT) for cold and warmth only recently have been shown as an early marker of small nerve fiber dysfunction in these patients, heart rate variability (HRV) has frequently been used to quantify autonomic neuropathy. The main purpose with this report was to elucidate a possible relationship between estimates of HRV and TPT in a selected group of early and late-onset Swedish Val30Met ATTR patients. The results show significantly more pronounced elevation of TPT in early compared to late-onset patients. Significant correlations between HRV and TPT were found among late-onset cases, indicating a possible relationship between loss of thin nerve fibers in somatic and autonomic nerves, while generally no such relationships were found among early-onset cases. This observation emphasizes the importance of testing both HRV and TPT to ensure optimal early detection of neuropathic changes in an as wide as possible range of small nerve fibers in suspected ATTR patients. This is of particular importance as the phenotype of the ATTR disease varies between groups with different age of onset.

  • 4.
    Hendrikx, Tijn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Rosenqvist, Mårten
    Sandström, Herbert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Screening for atrial fibrillation with baseline and intermittent ECG recording in an out-of-hospital population2013In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 13, p. 41-, article id 41Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: the objective of this study is to investigate the detection rate of undiagnosed atrial fibrillation (AF) with short intermittent ECG recordings during four weeks among out-of-hospital patients, having at least one additional risk factor (CHADS2) for stroke.

    METHOD: Design: Cross-sectional study. Setting: Eight family practice centres and two hospital-based out-patient clinics in Sweden. Subjects: 989 out-of-hospital patients, without known AF, having one or more risk factors associated with stroke (CHADS2). Interventions: All individuals were asked to perform 10-second handheld ECG recordings during 28 days, twice daily and when having palpitations. Main outcome measures: Episodes of AF on handheld ECG recordings were defined as irregular supraventricular extrasystoles in series with a duration of 10 seconds.

    RESULTS: 928 patients completed registration. AF was found in 35 of 928 patients; 3.8% (95% confidence interval [CI] 2.7--5.2). These 35 patients had a mean age of 70.7 years (SD +/- 7.7; range 53--85) and a median CHADS2 of 2 (range 1--4).

    CONCLUSIONS: Intermittent handheld ECG recording over a four week period had a detection rate of 3.8% newly diagnosed AF, in a population of 928 out-of-hospital patients having at least one additional risk factor for stroke. Intermittent handheld ECG registration is a feasible method to detect AF in patients with an increased risk of stroke in whom oral anticoagulation (OAC) treatment is indicated.

  • 5.
    Hendrikx, Tijn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Rosenqvist, Mårten
    Sandström, Herbert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Persson, Mats
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Identifiering av paroxysmala, kortvariga arytmier: intermittent registrering mer effektiv än 24-timmars Holter-EKG2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 1-2, article id C6SEArticle in journal (Refereed)
    Abstract [en]

    Many patients suffer from palpitations or dizziness/presyncope. These patients are often referred for Holter ECG (24 hour), although the sensitivity for detecting arrhythmias is low. A new method, short intermittent regular and symptomatic ECG registrations at home, might be a convenient and more sensitive alternative also suitable for primary health care. In this case report we present a patient who had contacted health care several times during a seven year period for paroxysmal palpitations. Routine examination with 24 hour Holter ECG and event recorder did not result in a diagnosis. Using intermittent handheld ECG registration at home, a paroxysmal supraventricular arrhythmia was diagnosed. Further investigation revealed that the patient had a concealed Wolff-Parkinson-White (WPW) syndrome.

  • 6.
    Hendrikx, Tijn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Rosenqvist, Mårten
    Department of Clinical Sciences, Danderyds Sjukhus, Karolinska Institutet, SE-182 88 Stockholm, Sweden.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sandström, Herbert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Intermittent short ECG recording is more effective than 24-hour Holter ECG in detection of arrhythmias2014In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 14, p. 41-Article in journal (Refereed)
    Abstract [en]

    Background: Many patients report symptoms of palpitations or dizziness/presyncope. These patients are often referred for 24-hour Holter ECG, although the sensitivity for detecting relevant arrhythmias is comparatively low. Intermittent short ECG recording over a longer time period might be a convenient and more sensitive alternative. The objective of this study is to compare the efficacy of 24-hour Holter ECG with intermittent short ECG recording over four weeks to detect relevant arrhythmias in patients with palpitations or dizziness/presyncope.

    Methods:

    Design: prospective, observational, cross-sectional study. Setting: Clinical Physiology, University Hospital. Patients: 108 consecutive patients referred for ambiguous palpitations or dizziness/presyncope.

    Interventions: All individuals underwent a 24-hour Holter ECG and additionally registered 30-second handheld ECG (Zenicor EKG ((R)) thumb) recordings at home, twice daily and when having cardiac symptoms, during 28 days.

    Main outcome measures: Significant arrhythmias: atrial fibrillation (AF), paroxysmal supraventricular tachycardia (PSVT), atrioventricular (AV) block II-III, sinus arrest (SA), wide complex tachycardia (WCT).

    Results: 95 patients, 42 men and 53 women with a mean age of 54.1 years, completed registrations. Analysis of Holter registrations showed atrial fibrillation (AF) in two patients and atrioventricular (AV) block II in one patient (= 3.2% relevant arrhythmias [95% CI 1.1-8.9]). Intermittent handheld ECG detected nine patients with AF, three with paroxysmal supraventricular tachycardia (PSVT) and one with AV-block-II (= 13.7% relevant arrhythmias [95% CI 8.2-22.0]). There was a significant difference between the two methods in favour of intermittent ECG with regard to the ability to detect relevant arrhythmias (P = 0.0094). With Holter ECG, no symptoms were registered during any of the detected arrhythmias. With intermittent ECG, symptoms were registered during half of the arrhythmia episodes.

    Conclusions: Intermittent short ECG recording during four weeks is more effective in detecting AF and PSVT in patients with ambiguous symptoms arousing suspicions of arrhythmia than 24-hour Holter ECG.

  • 7.
    Hendrikx, Tijn
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sundqvist, Martin
    Sandström, Herbert
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sahlin, Carin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Rohani, Morteza
    Al-Khalili, Faris
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rosenqvist, Mårten
    Franklin, Karl A
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Atrial fibrillation among patients under investigation for suspected obstructive sleep apnea2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 2, article id e0171575Article in journal (Refereed)
    Abstract [en]

    STUDY OBJECTIVES: Obstructive sleep apnea is common among patients with atrial fibrillation, but the prevalence and risk factors for atrial fibrillation among patients who are being investigated on suspicion of sleep apnea are not well known. The aim of the study was to estimate the prevalence of atrial fibrillation among patients investigated for suspected obstructive sleep apnea and to identify risk factors for atrial fibrillation among them.

    METHODS: The prevalence of atrial fibrillation was investigated among 201 patients referred for suspected obstructive sleep apnea. Patients without known atrial fibrillation were investigated with a standard 12-lead ECG at hospital and short intermittent handheld ECG recordings at home, during 14 days.

    RESULTS: Atrial fibrillation occurred in 13 of 201 subjects (6.5%), and in 12 of 61 men aged 60 years and older (20%). The prevalence of atrial fibrillation increased with sleep apnea severity (p = 0.038). All patients with atrial fibrillation were men and all had sleep apnea. Age 60 or older, the occurrence of central sleep apnea and diabetes mellitus were independent risk factors for atrial fibrillation after adjustments for body mass index, gender, sleep apnea and cardiovascular disease.

    CONCLUSIONS: Atrial fibrillation is common among subjects referred for sleep apnea investigation and the prevalence of atrial fibrillation increases with sleep apnea severity. Independent risk factors for atrial fibrillation among patients investigated for suspected obstructive sleep apnea include the occurrence of coexisting central sleep apnea, age 60 years or older and diabetes mellitus.

  • 8.
    Henein, Michael Y.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Arvidsson, Sandra
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Pilebro, Björn
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Westermark, Per
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis2018In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 25, no 1, p. 46-53Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cardiac amyloidosis (CA) is a myocardial disease and commonly under-diagnosed condition. In CA patients, atrial fibrillation might occur in the absence of left atrial (LA) enlargement.

    OBJECTIVES: The aim of this study is to assess LA size and function, and its relationship with atrial arrhythmia in patients with hereditary transthyretin amyloidosis (ATTR).

    METHODS: Forty-six patients with confirmed ATTR amyloidosis on abdominal biopsy were studied. Assessment with 2D echocardiography and 2D strain showed 31 patients had increased LV wall thickness (LVWT) (septal thickness >12 mm), and 15 had normal LVWT. In addition to conventional measurements, LV and LA global longitudinal strain (GLS%) and strain rate (SR) were obtained. Western blot analysis was done to assess fibril type. ATTR patients with increased LVWT were compared with 23 patients with hypertrophic cardiomyopathy (HCM) and 31 healthy controls. ATTR amyloidosis patients also underwent 24 hour Holter monitoring to determine the presence of atrial arrhythmia.

    RESULTS: Atrial deformation during atrial systole was reduced in ATTR amyloidosis patients with increased LVWT independent of LA size and in contrast to HCM. Twenty of the ATTR amyloidosis patients (54%) had ECG evidence of significant atrial arrhythmic events. LA strain rate, during atrial systole, was the only independent predictor of atrial arrhythmia (β = 3.28, p = .012).

    CONCLUSION: In ATTR cardiomyopathy with increased LVWT, LA myocardial function is abnormal, irrespective of atrial cavity size. Reduced LA myocardial SR during atrial systole, irrespective of cavity volume, E/e' and LV deformation, is also a strong predictor for atrial arrhythmic events.

  • 9.
    Hörnsten, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Pennlert, Johanna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Jensen, Steen M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Heart complications in familial transthyretin amyloidosis: impact of age and gender.2010In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 17, no 2, p. 63-68Article in journal (Refereed)
    Abstract [en]

    Heart arrhythmia is common in Swedish patients with familial amyloidotic polyneuropathy (FAP), as well as cardiomyopathy. We investigated the relationship between Holter ECG and echocardiographic findings in 108 FAP patients, with particular focus on age and gender differences. Female patients were younger than male patients at symptom onset (p < 0.01). Only 4 of 39 patients with septal hypertrophy were females. Regression analysis showed that age of onset, gender and duration of disease were significantly related with intraventricular septum (IVS) thickness. Sixty-five patients (25 females) presented with abnormal 24-h ECG recordings. IVS thickness was not significantly related to conduction disturbances or the presence of ventricular arrhythmia (VA). However, IVS thickness and atrial dimension were both related to increased rate of supraventricular arrhythmia (SVA). Male gender was clearly associated with more pronounced septal thickness of the heart. Conduction disturbances were not related to IVS thickness, indicating that the distribution and extent of infiltration of the heart by amyloid are heterogeneous and related to gender and age of onset. These findings highlight the necessity of 24-h ECGs to detect conduction disturbances, due to their occurrence in the absence of echocardiographic evidence of amyloid deposition in the myocardium.

  • 10.
    Hörnsten, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jensen, Steen M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Outcome of heart rate variability and ventricular late potentials after liver transplantation for familial amyloidotic polyneuropathy2008In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 15, no 3, p. 187-195Article in journal (Refereed)
    Abstract [en]

    Reduced heart rate variability (HRV) is common in familial amyloidotic polyneuropathy (FAP), as well as cardiac arrhythmias. We examined the effects of liver transplantation (LTx) on 24-h HRV and ventricular late potentials. Twenty-one liver-transplanted FAP patients underwent Holter-ECG recordings and signal average electrocardiography recordings (SAECG) before and after LTx. Mean follow-up time after LTx was 21.7 months. Three patients had marked increased HRV after LTx, but this was in all cases caused by the development of subtle atrial arrhythmia and did not reflect an improvement in the cardiac autonomic control. In total, ten patients were excluded from analysis of HRV because of arrhythmia. Spectral analysis of HRV showed no significant differences before and after LTx in the remaining 11 patients. Positive late potentials were found in 33% of patients before LTx and this proportion was unchanged after LTx. Reduced HRV and positive late potentials are common in Swedish FAP patients, and remain stable, at least within the short term after transplantation. If an increase of HRV after transplantation is observed, it should raise the suspicion that the patient has developed subtle atrial arrhythmia.

  • 11.
    Hörnsten, Rolf
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Olofsson, Bert-Ove
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Arrhythmia - a pitfall in tests of cardiac autonomic function after liver transplantation for familial amyloidotic polyneuropathy: a long-term follow-up of Swedish patients2012In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 19, no 2, p. 81-86Article in journal (Refereed)
    Abstract [en]

    Liver transplantation (LT) is a potentially curative treatment for hereditary transthyretin amyloidosis, of which familial amyloid polyneuropathy (FAP) is the most common form in Sweden. This study investigated the long-term development in heart rate variability (HRV) after LT in Swedish FAP patients. HRV was analyzed before LT, and during a first (<40 months) and a second (>40 months) follow-up recording after transplantation, respectively. Power spectrum analysis was performed on 2-min sequences in the supine position and after passive tilt, after careful identification of patients with arrhythmia. Data were obtained from 33 patients, but 18 patients had developed cardiac arrhythmia or were pacemaker-treated (4 before LT and 14 after LT) and three patients had not performed the first follow-up recording. In the remaining 12 patients, HRV decreased between the pretransplant evaluation and the first follow-up, thereafter no significant changes were found. In conclusion, our study showed that the progressive development of cardiac arrhythmias after LT is a major pitfall when assessing cardiac autonomic function in FAP patients, especially in patients older than 40 years. In the minority of patients with sinus rhythm in all recordings, cardiac autonomic modulation remained stable after transplantation and no improvement was noted.

  • 12.
    Karlsson, Marcus
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Automatic filtering of outliers in RR intervals before analysis of heart rate variability in Holter recordings: a comparison with carefully edited data.2012In: Biomedical engineering online, ISSN 1475-925X, E-ISSN 1475-925X, Vol. 11, no 2, p. 12-Article in journal (Refereed)
    Abstract [en]

    Background: Undetected arrhythmic beats seriously affect the power spectrum of the heart rate variability (HRV). Therefore, the series of RR intervals are normally carefully edited before HRV is analysed, but this is a time consuming procedure when 24-hours recordings are analysed. Alternatively, different methods can be used for automatic removal of arrhythmic beats and artefacts. This study compared common frequency domain indices of HRV when determined from manually edited and automatically filtered RR intervals.

    Methods and Results: Twenty-four hours Holter recordings were available from 140 healthy subjects of age 1-75 years. An experienced technician carefully edited all recordings. Automatic filtering was performed using a recursive procedure where RR intervals were removed if they differed from the mean of the surrounding RR intervals with more than a predetermined limit (ranging from 10% to 50%). The filtering algorithm was evaluated by replacing 1% of the beats with synthesised ectopic beats. Power spectral analysis was performed before and after filtering of both the original edited data and the noisy data set. The results from the analysis using the noisy data were used to define an age-based filtering threshold. The age-based filtration was evaluated with completely unedited data, generated by removing all annotations from the series of RR intervals, and then comparing the resulting HRV indices with those obtained using edited data. The results showed equivalent results after age-based filtration of both the edited and unedited data sets, where the differences in HRV indices obtained by different preprocessing methods were small compared to the mean values within each age group.

    Conclusions: The study showed that it might not be necessary to perform the time-consuming careful editing of all detected heartbeats before HRV is analysed in Holter recordings.

    In most subjects, it is sufficient to perform the regular editing needed for valid arrhythmia analyses, and then remove undetected ectopic beats and artefacts by age-based filtration of the series of RR intervals, particularly in subjects older than 30 years.

  • 13.
    Obayashi, K
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Marcus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Okamoto, S
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ando, Y
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hemodynamic responses after tilt reversal in FAP2011In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 18, no Suppl 1, p. 161-163Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to evaluate hemodynamic responses after tilt reversal in familial amyloid polyneuropathy (FAP). Systolic blood pressure (BP) and heart rate variability (HRV) were analyzed in the baseline, 70-degree upright position, and after tilt reversal in 10 patients with FAP and 14 healthy controls. Maximum systolic BP after tilt reversal was increased in FAP as compared to baseline (BP overshoot), whereas controls showed a significantly lower BP overshoot. In all states, all HRV parameters were significantly lower than those of the controls. In a linear regression analysis adjusted for age, we found a significant inverse relation between BP overshoot and HRV in all three states. Five patients presented atrial arrhythmia precluding HRV analysis: four of those presented BP overshoots 12 mmHg. BP overshoot may be a useful marker to assess the progression of cardiac autonomic dysfunction, especially since heart arrhythmia in many patients with FAP prevents HRV analysis.

  • 14.
    Obayashi, Konen
    et al.
    Department of Diagnostic Medicine, Graduate School of Life Sciences, Kumamoto University, Honjo, Kumamoto, Japan.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Marcus
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Okamoto, Sadahisa
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Ando, Yukio
    Department of Diagnostic Medicine, Graduate School of Life Sciences, Kumamoto University, Honjo, Kumamoto, Japan.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Blood pressure overshoot after tilt reversal in patients with familial amyloidotic polyneuropathy2011In: Hypertension Research, ISSN 0916-9636, E-ISSN 1348-4214, Vol. 34, no 1, p. 133-138Article in journal (Refereed)
    Abstract [en]

    The pathophysiology of the hemodynamic responses to postural stress in familial amyloidotic polyneuropathy (FAP) remains to be elucidated. The aim of the study was to evaluate hemodynamic responses after tilt reversal in FAP. Systolic blood pressure (BP) and heart rate variability (HRV) were analyzed in the baseline, 70° upright position, and after tilt reversal in 15 FAP patients and 14 healthy controls. Beat-to-beat BP was recorded with a Finapres device. Maximum systolic BP after tilt reversal was increased with 22±13 mm Hg in FAP patients as compared with baseline (BP overshoot), whereas controls showed a significantly lower BP overshoot (8±6 mm Hg, P<0.001). In all states, total spectral power and the power of the low and high frequency components were all significantly lower than those of the controls (P<0.01). In a linear regression analysis adjusted for age, we found a significant inverse relation between BP overshoot and HRV (total spectral power, power of the low-frequency and high-frequency components) in all three states (standardized β between -0.74 to -0.53, P<0.01). Five FAP patients presented a trial arrhythmia precluding HRV analysis: four of those presented BP overshoots 12 mm Hg. BP overshoot may be a marker to assess the progression of cardiac autonomic dysfunction, especially as heart arrhythmia in many FAP patients prevent HRV analysis. In addition, assessment of the post-tilt BP reaction points to possible treatment modalities for orthostatic hypotension at least in the early stages of the disease.

  • 15.
    Okamoto, Sadahisa
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hörnsten, Rolf
    Obayashi, Konen
    Wijayatunga, Priyantha
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Continuous development of arrhythmia is observed in Swedish transplant patients with familial amyloidotic polyneuropathy (amyloidogenic transthyretin Val30Met variant)2011In: Liver transplantation, ISSN 1527-6465, E-ISSN 1527-6473, Vol. 17, no 2, p. 122-128Article in journal (Refereed)
    Abstract [en]

    In patients with familial amyloidotic polyneuropathy (FAP), heart complications are prognostic factors for mortality and morbidity after liver transplantation (LT). However, only a few studies have analyzed the development of arrhythmia in transplant patients with FAP. We investigated the development of arrhythmia requiring pacemaker insertion (PMI) in Swedish transplant patients with FAP, and we related the findings to gender, age at disease onset, and survival. One hundred four transplant patients with the amyloidogenic transthyretin Val30Met mutation were included in the study. Twenty-six (25%) received a pacemaker during the observation period (a median of 11 years after disease onset). This frequency was comparable to that noted in a previous study describing the natural course of FAP. No significant differences in PMI between early-onset cases (<50 years old) and late-onset cases (≥ 50 years old) or between genders were observed. PMI was not significantly related to patient survival. Our study confirms our previously reported short-time observation: LT does not prevent the development of heart arrhythmia necessitating PMI. The development of arrhythmia is unrelated to gender or age at disease onset, and the yearly risk does not appear to decrease with time after LT.

  • 16.
    Rydberg, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Karlsson, Markus
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Wiklund, Urban
    Can analysis of heart rate variability predict arrhythmia in children with fontan circulation?2008In: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 29, no 1, p. 50-55Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to examine whether changes in heart rate variability (HRV) can predict arrhythmias in children who have undergone the Fontan procedure. The study included 15 children with total cavopulmonary connection. All examinations included echocardiography and 24-h ambulatory electrocardiogram with power spectral analysis of HRV and Poincaré plots (plots of each R-R interval as a function of the previous R-R interval). Six patients developed supraventricular tachycardia (four or more consecutive supraventricular beats). One patient was excluded from the study due to the development of bradycardia, necessitating placement of a pacemaker. Compared to the arrhythmia group, the patients without arrhythmias (n = 8) exhibited a significant difference in the standard deviation of instantaneous beat-to-beat R-R interval variability (= 0.02). Poincaré plots of patients without arrhythmias showed a typical torpedo- or comet-shaped pattern, whereas the arrhythmia group showed a more complex pattern. Although this study examined only a few subjects, needing confirmation by larger studies, it does indicate that patients who develop arrhythmias after receiving the Fontan procedure show a different Poincaré pattern compared to the nonarrhythmic group—even before the arrhythmia can be detected using the conventional Holter procedure. Routine follow-up using the Holter procedure and Poincaré plot analysis could help detect early arrhythmias.

  • 17.
    Rydberg, Annika
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Rask, P
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Teien, Dag
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Heart rate variability in children with Fontan circulation.2004In: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 25, no 4, p. 365-369Article in journal (Refereed)
    Abstract [en]

    Heart rate variability (HRV) can be used to study cardiovascular autonomic control. This study examines HRV in children with Fontan circulation and its change over time. Thirty-four children in two groups were examined. Group A consisted of 10 patients who had undergone total cavopulmonary connection. Group B consisted of 24 healthy children/adolescents matched for gender, height, and weight. To analyze HRV parameters, all examinations included echocardiography and 24-hour ambulatory electrocardiogram. Comparing all patients and controls, there were no significant differences in HRV parameters. Analyzing subgroups of patients younger than 10 years old, two of the HRV parameters were significantly different compared to controls. For the group of patients older than 10 years, eight of the HRV parameters were significantly reduced. Most significant differences were found regarding low-frequency range (p < 0.008) and high-frequency range p < 0.008. This study confirms the finding of earlier studies that patients with Fontan circulation have a reduced HRV, and our findings indicate that there is a progressive reduction of HRV over time.

  • 18.
    Wiklund, Urban
    et al.
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Olofsson, Bert-Ove
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Cardiac autonomic function does not improve after liver transplantation for familial amyloidotic polyneuropathy.2010In: Autonomic Neuroscience: Basic & Clinical, ISSN 1566-0702, E-ISSN 1872-7484, Vol. 156, no 1-2, p. 124-130Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Liver transplantation is the only potentially curative treatment for familial amyloidotic polyneuropathy (FAP). We investigated cardiac autonomic function in 63 transplanted Swedish FAP patients. METHODS: Heart rate variability (HRV) was recorded between 1-17 (mean 8) months before, and 10-40 (mean 20) months after transplantation. HRV was analysed by power spectrum analysis, but only in patients without arrhythmia (n=38). RESULTS: Patients with moderate cardiac autonomic dysfunction showed a statistically significant reduction in HRV after transplantation, as compared to the pre-transplant recording. Patients with severe cardiac autonomic dysfunction presented unchanged HRV after liver transplantation. Twenty patients were excluded because they presented cardiac arrhythmia, five of these presented increased HRV after transplantation but had developed subtle arrhythmias, thus, they had not improved cardiac autonomic control. Five patients were excluded because they were pacemaker-treated. CONCLUSIONS: The reason why HRV decreased after transplantation remains unclear, but there are several possibilities: 1) liver transplantation did not stop the deterioration in cardiac autonomic function; 2) the deterioration continued until transplantation and was then halted; or 3) a sudden reduction in HRV occurred in connection with the transplantation procedure. Nonetheless, this study failed to disclose any improvement in cardiac autonomic function after liver transplantation for FAP.

  • 19.
    Wiklund, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Jensen, Steen M
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Abnormal heart rate variability and subtle atrial arrhythmia in patients with familial amyloidotic polyneuropathy2008In: Annals of Nonivasive Electrocardiology, Vol. 13, no 3, p. 249-256Article in journal (Refereed)
  • 20.
    Wiklund, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Kadkhodaee, Amir
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Andersson, Kennet
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Normal scores of deep breathing tests: beware of dysrhythmia in transthyretin amyloidosis2018In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 25, no 1, p. 54-61Article in journal (Refereed)
    Abstract [en]

    Background: The heart rate (HR) response to paced deep breathing (DB) is a common test of cardiac autonomic function, where high heart rate variability (HRV) is considered to reflect normal autonomic function. We evaluated the DB test in patients with hereditary transthyretin amyloid (ATTRm) amyloidosis, where autonomic dysregulation and atrial arrhythmias are common.Methods: Paced DB was performed during one minute (six breaths/min) in 165 recordings in adult ATTRm amyloidosis patients with the TTR Val30Met mutation, 42 hypertrophic cardiomyopathy (HCM) patients and 211 healthy subjects. HRV was scored by traditional DB indices and by a novel regularity index, estimating the fraction of the HRV that was coherent with the breathing pattern.Results: Twenty per cent of ATTRm amyloidosis patients presented with age-adjusted HRV scores within normal limits but poor regularity due to subtle atrial arrhythmias and cardiac conduction disturbances. Forty-seven per cent of ATTRm amyloidosis patients presented with HRV scores below normal limits, whereas HCM patients presented with higher HRV than ATTRm amyloidosis patients.Conclusions: 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.

  • 21.
    Wilén, Jonna
    et al.
    National Institute for Working Life, Umeå, Sweden.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology. National Institute for Working Life, Umeå, Sweden.
    Sandström, Monica
    National Institute for Working Life, Umeå, Sweden.
    Bjerle, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology. Biomedical Engineering & Informatics, University Hospital, Umeå, Sweden.
    Stensson, Olov
    National Institute for Working Life, Umeå, Sweden.
    Lyskov, Eugene
    Centre for Musculoskeletal Research, University of Gävle, Sweden.
    Hansson Mild, Kjell
    National Institute for Working Life, Umeå, Sweden.
    Electromagnetic field exposure and health among RF plastic sealer operators2004In: Bioelectromagnetics, ISSN 0197-8462, E-ISSN 1521-186X, Vol. 25, no 1, p. 5-15Article in journal (Refereed)
    Abstract [en]

    Operators of RF plastic sealers (RF operators) are an occupational category highly exposed to radiofrequency electromagnetic fields. The aim of the present study was to make an appropriate exposure assessment of RF welding and examine the health status of the operators. In total, 35 RF operators and 37 controls were included. The leakage fields (electric and magnetic field strength) were measured, as well as induced and contact current. Information about welding time and productivity was used to calculate time integrated exposure. A neurophysiological examination and 24 h ECG were also carried out. The participants also had to answer a questionnaire about subjective symptoms. The measurements showed that RF operators were exposed to rather intense electric and magnetic fields. The mean values of the calculated 6 min, spatially averaged E and H field strengths, in line with ICNIRP reference levels, are 107 V/m and 0.24 A/m, respectively. The maximum measured field strengths were 2 kV/m and 1.5 A/m, respectively. The induced current in ankles and wrists varied, depending on the work situation, with a mean value of 101 mA and a maximum measured value of 1 A. In total, 11 out of 46 measured RF plastic sealers exceeded the ICNIRP reference levels. RF operators, especially the ready made clothing workers had a slightly disturbed two-point discrimination ability compared to a control group. A nonsignificant difference between RF operators and controls was found in the prevalence of subjective symptoms, but the time integrated exposure parameters seem to be of importance to the prevalence of some subjective symptoms: fatigue, headaches, and warmth sensations in the hands. Further, RF operators had a significantly lower heart rate (24 h registration) and more episodes of bradycardia compared to controls.

  • 22.
    Wilén, Jonna
    et al.
    National Institute for Working Life, Umeå.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Radiation Sciences.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Clinical Physiology.
    Sandström, Monica
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Changes in heart rate variability among RF plastic sealer operators.2007In: Bioelectromagnetics, ISSN 0197-8462, E-ISSN 1521-186X, Vol. 28, no 1, p. 76-79Article in journal (Refereed)
    Abstract [en]

    In a previous study, we showed that operators of radiofrequency (RF) plastic sealers, RF operators (n = 35) had a lower heart rate during nighttime compared to a control group (n = 37). We have analyzed the heart rate variability (HRV) on the same group of people to better understand the possible underlying rhythm disturbances. We found a significantly increased total HRV and very low frequency (VLF) power during nighttime among the RF operators compared to a control group. Together with our previous finding of a significantly lower heart rate during nighttime among the RF operators compared to the controls, this finding indicates a relative increase in parasympathetic cardiac modulation in RF operators. This could in turn be due to an adaptation of the thermoregulatory system and the cardiac autonomic modulation to a long-term low-level thermal exposure in the RF operators.

  • 23.
    Wixner, Jonas
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Karling, Pontus
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Rydh, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Hornsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Anan, Intissar
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gastric emptying in hereditary transthyretin amyloidosis: the impact of autonomic neuropathy2012In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 24, no 12, p. 1111-e568Article in journal (Refereed)
    Abstract [en]

    Background: Gastrointestinal (GI) complications are common in hereditary transthyretin amyloidosis and an autonomic dysfunction has been considered to explain these symptoms. The aim of this study was to investigate the impact of autonomic neuropathy on gastric emptying in hereditary transthyretin amyloidosis and to relate these findings to nutritional status, GI symptoms, gender, and age at disease onset.

    Methods: Gastric emptying was evaluated with gastric emptying scintigraphy. Spectral analysis of the heart rate variability and cardiovascular responses after tilt test were used to assess the autonomic function. The nutritional status was evaluated with the modified body mass index (s-albumine x BMI).

    Key Results: Gastric retention was found in about one-third of the patients. A weak correlation was found between the scintigraphic gastric emptying rate and both the sympathetic (rs = -0.397, P < 0.001) and parasympathetic function (rs = -0.282, P = 0.002). The gastric emptying rate was slower in those with lower or both upper and lower GI symptoms compared with those without symptoms (median T50 123 vs 113 min, P = 0.042 and 192 vs 113 min, P = 0.003, respectively). Multiple logistic regression analysis showed that age of onset (OR 0.10, CI 0.020.52) and sympathetic dysfunction (OR 0.23, CI 0.100.51), but not gender (OR 0.76, CI 0.311.84) and parasympathetic dysfunction (OR 1.81, CI 0.724.56), contributed to gastric retention.

    Conclusions and Inferences: Gastric retention is common in hereditary transthyretin amyloidosis early after onset. Autonomic neuropathy only weakly correlates with gastric retention and therefore additional factors must be involved.

  • 24.
    Zhao, Ying
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Left ventricular dyssynchrony is associated with reduced heart rate variability in familial amyloidotic polyneuropathy2012In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 155, no 2, p. 272-278Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cardiac complications are common in familial amyloidotic polyneuropathy (FAP), in which heart rate variability (HRV) is reduced. Although autonomic disturbances are well-established, mechanisms for reduced HRV, their relationship with left ventricular (LV) function in FAP are not well understood.

    METHODS: Twenty-nine FAP patients and 29 healthy controls were studied using Doppler echocardiography. Patients' and controls' HRV were studied using power spectral analysis from 24-hour Holter-ECG recordings.

    RESULTS: In FAP patients, all HRV parameters were lower (p<0.01 for all) than those in controls. Echocardiography showed a normal LV systolic function in patients. Relative filling time (FT/RR) was shorter (p<0.01) and total isovolumic time (t-IVT) was longer (p<0.01) in patients than in controls. E/Em was higher (p<0.01), as was Tei index (p=0.02) as compared to controls. T-IVT and Tei index correlated with stroke volume (SV) (r=-0.54, p<0.01 and r=-0.44, p<0.05, respectively) in patients. HRV was reduced in 9/29 (31%) patients, who had shorter FT/RR (p<0.01), longer t-IVT (p<0.01), higher Tei index (p=0.05), A wave (p<0.01) and E/Em (p<0.05) than in subjects without reduced HRV. FT/RR and t-IVT correlated with HRV spectral parameters (p<0.05 for all). The correlation between t-IVT and SV was stronger in patients with reduced HRV (r=-0.80, p<0.01) than in those without. QRS duration was not different in the two subgroups of patients.

    CONCLUSIONS: In a subset of patients with FAP, HRV was significantly reduced and appeared to be associated with shortened LV filling time and prolonged t-IVT, which reflect ventricular dyssynchrony, despite normal QRS. Thus, in addition to autonomic disturbances in FAP, ventricular dyssynchrony is another factor associated with reduced HRV. Correction of such disturbed ventricular function by cardiac resynchronization therapy may control patients' symptom.

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