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1.
Ups J Med Sci ; 1262021.
Article in English | MEDLINE | ID: mdl-34349886

ABSTRACT

BACKGROUND: This research study aimed at assessing the electrocardiographic (ECG) changes caused by ageing in a cohort of healthy subjects with normal echocardiographic examinations. METHODS: A total of 219 healthy individuals (119 males and 100 females) were evaluated for possible arrhythmias with a standard 12-lead resting ECG and 24-h Holter ECG. As the recordings were performed between 1998 and 2000, a 20-year follow-up study was carried out by assessing the local medical records to investigate whether the subjects had experienced any cardiovascular health complications or disease since the baseline assessment. RESULTS: Eighty-three subjects (45 males and 38 females) presented with pathological ECG findings at baseline. The most common finding on analysis of Holter ECG recordings was premature atrial contractions, and the most severe pathological finding was episodes of ventricular tachycardia (eight subjects). Regarding the analysis of the standard 12-lead ECG, the most common finding was left ventricular hypertrophy, and the most severe pathological findings were ST-T changes and prolongation of the QT interval. Despite other cardiac examinations performed on these patients showing normal results, in combination with a strict inclusion criterion, this study showed that 28% of all subjects had pathological resting 12-lead ECGs at rest and 35% had pathological heart rhythms when assessed by 24-h Holter ECG. At follow-up, 21% of females and 43% of males had presented with ECG abnormalities, and 30% of females and 36% of males had cardiovascular disease. There was hypertension in 45% of females and in 58% of males. However, no association was found between the follow-up findings and ECG changes seen at baseline. CONCLUSION: Although most ECG changes found at baseline could be considered as a normal variation, they may progress to more severe heart complications as the subject ages. The results of this study also validate ECG findings of previous studies and underline that diagnostic criteria should be based on gender and age.


Subject(s)
Electrocardiography, Ambulatory , Heart Diseases , Adult , Arrhythmias, Cardiac , Electrocardiography , Female , Follow-Up Studies , Humans , Male , Young Adult
3.
Amyloid ; 25(1): 54-61, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29394116

ABSTRACT

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.


Subject(s)
Amyloid Neuropathies, Familial , Arrhythmias, Cardiac , Heart Rate , Mutation, Missense , Prealbumin/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Amino Acid Substitution , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/genetics , Amyloid Neuropathies, Familial/physiopathology , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/genetics , Arrhythmias, Cardiac/physiopathology , Female , Humans , Male , Middle Aged , Respiratory Function Tests , Retrospective Studies
4.
Amyloid ; 25(1): 46-53, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29369708

ABSTRACT

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 (ß = 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.


Subject(s)
Amyloid Neuropathies, Familial , Atrial Fibrillation , Echocardiography , Myocardium , Aged , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/diagnostic imaging , Amyloid Neuropathies, Familial/physiopathology , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/etiology , Atrial Fibrillation/physiopathology , Heart Atria/diagnostic imaging , Heart Atria/physiopathology , Humans , Middle Aged , Retrospective Studies
5.
PLoS One ; 12(2): e0171575, 2017.
Article in English | MEDLINE | ID: mdl-28178304

ABSTRACT

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.


Subject(s)
Atrial Fibrillation/complications , Atrial Fibrillation/epidemiology , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/epidemiology , Adult , Aged , Comorbidity , Female , Humans , Male , Middle Aged , Odds Ratio , Patient Outcome Assessment , Population Surveillance , Prevalence , Risk Factors , Sweden/epidemiology
6.
Lakartidningen ; 1122015 Jan 06.
Article in Swedish | MEDLINE | ID: mdl-25584602

ABSTRACT

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.


Subject(s)
Electrocardiography, Ambulatory/methods , Tachycardia, Paroxysmal/diagnosis , Tachycardia, Supraventricular/diagnosis , Adult , Electrocardiography, Ambulatory/instrumentation , Electrocardiography, Ambulatory/standards , Humans , Male , Wolff-Parkinson-White Syndrome/diagnosis
7.
BMC Cardiovasc Disord ; 14: 41, 2014 Apr 01.
Article in English | MEDLINE | ID: mdl-24690488

ABSTRACT

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. 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® 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.


Subject(s)
Arrhythmias, Cardiac/diagnosis , Electrocardiography, Ambulatory , Electrocardiography/methods , Heart Rate , Adult , Aged , Arrhythmias, Cardiac/physiopathology , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Atrioventricular Block/diagnosis , Atrioventricular Block/physiopathology , Cross-Sectional Studies , Female , Hospitals, University , Humans , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Sweden , Tachycardia, Supraventricular/diagnosis , Tachycardia, Supraventricular/physiopathology , Time Factors , Young Adult
8.
J Electrocardiol ; 47(3): 374-82, 2014.
Article in English | MEDLINE | ID: mdl-24674760

ABSTRACT

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 (Poincaré 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.


Subject(s)
Atrial Fibrillation/diagnosis , Atrial Fibrillation/etiology , Electrocardiography/instrumentation , Fontan Procedure/adverse effects , Point-of-Care Systems , Adolescent , Child , Child, Preschool , Equipment Design , Equipment Failure Analysis , Female , Humans , Male , Miniaturization , Reproducibility of Results , Sensitivity and Specificity
9.
BMC Cardiovasc Disord ; 13: 41, 2013 Jun 10.
Article in English | MEDLINE | ID: mdl-23758799

ABSTRACT

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. 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.


Subject(s)
Arrhythmias, Cardiac/diagnosis , Blood Pressure Monitoring, Ambulatory/methods , Adult , Aged , Atrial Fibrillation/diagnosis , Atrioventricular Block/diagnosis , Cross-Sectional Studies , Dizziness/etiology , Female , Humans , Male , Middle Aged , Patient Compliance , Prospective Studies , Sinus Arrest, Cardiac/diagnosis , Sweden , Syncope/etiology , Tachycardia, Supraventricular/diagnosis , Young Adult
10.
Amyloid ; 19(2): 81-6, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22587458

ABSTRACT

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.


Subject(s)
Amyloid Neuropathies, Familial/physiopathology , Arrhythmias, Cardiac/physiopathology , Autonomic Nervous System/physiopathology , Heart Rate , Liver Transplantation , Adult , Aged , Amyloid Neuropathies, Familial/complications , Amyloid Neuropathies, Familial/surgery , Arrhythmias, Cardiac/complications , Female , Follow-Up Studies , Heart/innervation , Heart/physiopathology , Heart Function Tests , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Sinoatrial Node/physiopathology , Treatment Outcome
11.
Biomed Eng Online ; 11: 2, 2012 Jan 11.
Article in English | MEDLINE | ID: mdl-22236441

ABSTRACT

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.


Subject(s)
Electrocardiography, Ambulatory/methods , Electronic Data Processing/methods , Heart Rate/physiology , Adolescent , Adult , Age Factors , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Signal Processing, Computer-Assisted , Time Factors
12.
Pediatr Cardiol ; 33(2): 307-15, 2012 Feb.
Article in English | MEDLINE | ID: mdl-21984213

ABSTRACT

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.


Subject(s)
Fontan Procedure , Heart Defects, Congenital/physiopathology , Heart Defects, Congenital/surgery , Heart Rate/physiology , Pulmonary Artery/surgery , Vena Cava, Superior/surgery , Adolescent , Anastomosis, Surgical , Child , Child, Preschool , Electrocardiography, Ambulatory , Female , Humans , Infant , Male
13.
Int J Cardiol ; 155(2): 273-8, 2012 Mar 08.
Article in English | MEDLINE | ID: mdl-21056485

ABSTRACT

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.


Subject(s)
Amyloid Neuropathies, Familial/mortality , Heart Rate/physiology , Ventricular Dysfunction, Left/mortality , Ventricular Dysfunction, Left/physiopathology , Ventricular Function, Left/physiology , Aged , Cardiac Pacing, Artificial , Echocardiography, Doppler , Electrocardiography, Ambulatory , Female , Follow-Up Studies , Humans , Male , Middle Aged , Stroke Volume/physiology , Systole/physiology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/therapy
14.
Article in English | MEDLINE | ID: mdl-30890882

ABSTRACT

Over the last decade, new medical treatment modalities have emerged based on increased insights into amyloid formation. With the increased possibilities for treatment of amyloidosis caused by transthyretin (TTR) amyloid deposits comes the need for diagnostic procedures for early diagnosis and better tools to follow disease progression. This is of particular importance in clinical trials evaluating the efficacy of new treatments. Until recently, the treatment of TTR amyloidosis (ATTR) was based solely on liver transplantation, a procedure that has halted disease progression in many patients. Liver transplantation has been especially effective in patients under the age of 50 years carrying the TTR V30M mutation, whereas the outcome of the procedure has been variable for others, particularly elderly male patients and those carrying a non-V30M mutation. This review concentrates on new insights derived from our center's experience with liver transplantation, how to implement this experience in evaluation of new treatment modalities for ATTR, and how to facilitate early diagnosis of neuropathy with easily available diagnostic tools. Attention has focused on manifestations of the disease that involve the heart and the peripheral nervous system; change in peripheral nerve function has been the primary endpoint in two controlled clinical trials, one finished and one ongoing. New insights into the amyloid formation process and the lessons learned from liver transplantation give the opportunity to design potentially effective treatment modalities for ATTR. It appears reasonable to suspect that a combination of different treatment modalities may be required to treat the disease, and that different treatment regimes will be designed according to the phenotype of the disease. For the patients and their relatives there is now a solid foundation for optimism, with prospects of several effective medical treatment possibilities within the coming decade.

15.
Amyloid ; 18(4): 183-90, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22035563

ABSTRACT

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.


Subject(s)
Amyloidosis, Familial/physiopathology , Heart Rate , Thermosensing , Adult , Aged , Amyloid/metabolism , Amyloidosis, Familial/metabolism , Female , Foot/physiopathology , Humans , Leg/physiopathology , Male , Middle Aged , Multivariate Analysis , Prealbumin/metabolism , Sweden
16.
Liver Transpl ; 17(2): 122-8, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21280184

ABSTRACT

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.


Subject(s)
Amyloid Neuropathies, Familial/surgery , Arrhythmias, Cardiac/genetics , Liver Transplantation , Mutation , Prealbumin/genetics , Adult , Age of Onset , Aged , Amyloid Neuropathies, Familial/genetics , Amyloid Neuropathies, Familial/mortality , Arrhythmias, Cardiac/mortality , Arrhythmias, Cardiac/therapy , Cardiac Pacing, Artificial , Chi-Square Distribution , Female , Genetic Predisposition to Disease , Humans , Kaplan-Meier Estimate , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Male , Middle Aged , Proportional Hazards Models , Risk Assessment , Risk Factors , Sweden/epidemiology , Time Factors , Treatment Outcome , Young Adult
17.
Hypertens Res ; 34(1): 133-8, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20927118

ABSTRACT

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 ß 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.


Subject(s)
Amyloid Neuropathies, Familial/physiopathology , Autonomic Nervous System/physiopathology , Blood Pressure/physiology , Postural Balance/physiology , Aged , Electrocardiography , Heart Rate/physiology , Hemodynamics/physiology , Humans , Linear Models , Middle Aged , Statistics, Nonparametric , Tilt-Table Test
18.
Amyloid ; 17(2): 63-8, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20462364

ABSTRACT

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.


Subject(s)
Amyloid Neuropathies, Familial/complications , Arrhythmias, Cardiac/etiology , Prealbumin/genetics , Adult , Age of Onset , Aged , Aged, 80 and over , Amyloid Neuropathies, Familial/pathology , Amyloid Neuropathies, Familial/physiopathology , Arrhythmias, Cardiac/pathology , Cardiomyopathies/complications , Echocardiography , Electrocardiography , Female , Heart Septum/pathology , Humans , Male , Middle Aged , Sex Factors
19.
Auton Neurosci ; 156(1-2): 124-30, 2010 Aug 25.
Article in English | MEDLINE | ID: mdl-20478749

ABSTRACT

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.


Subject(s)
Amyloid Neuropathies, Familial/physiopathology , Amyloid Neuropathies, Familial/surgery , Autonomic Nervous System/physiology , Heart Rate/physiology , Liver Transplantation/physiology , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Liver Transplantation/trends , Male , Middle Aged , Young Adult
20.
Amyloid ; 15(3): 187-95, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18925457

ABSTRACT

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.


Subject(s)
Amyloid Neuropathies, Familial/surgery , Heart Rate/physiology , Tachycardia, Ventricular/physiopathology , Ventricular Function , Adult , Age of Onset , Aged , Amyloid Neuropathies, Familial/physiopathology , Electrocardiography , Follow-Up Studies , Humans , Liver Transplantation , Middle Aged , Prognosis
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