Intermittent short ECG recording is more effective than 24-hour Holter ECG in detection of arrhythmias.

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.

Handheld ECG in analysis of arrhythmia and heart rate variability in children with Fontan circulation.

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.

Screening for atrial fibrillation with baseline and intermittent ECG recording in an out-of-hospital population.

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.

Automatic filtering of outliers in RR intervals before analysis of heart rate variability in Holter recordings: a comparison with carefully edited data.

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.

Heart rate variability in children with Fontan circulation: lateral tunnel and extracardiac conduit.

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.

Continuous development of arrhythmia is observed in Swedish transplant patients with familial amyloidotic polyneuropathy (amyloidogenic transthyretin Val30Met variant).

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.

Are ECG changes in heart-healthy individuals of various ages related to cardiac disease 20 years later?

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.

Abnormal heart rate variability and subtle atrial arrhythmia in patients with familial amyloidotic polyneuropathy.

BACKGROUND: Cardiac autonomic dysfunction is a common complication of familial amyloidotic polyneuropathy (FAP), but cardiac arrhythmia and conduction disturbances are also common. We analyzed heart rate variability (HRV) in FAP patients using power spectrum analysis and Poincaré plot analysis. METHODS: HRV was analyzed in 24-hour ECG recordings (Holter) in 41 FAP patients. RESULTS: Power spectrum analysis showed reduced HRV in 21 FAP patients. A novel finding was that nine other patients with abnormal Poincaré plots had either very high power in the high-frequency region (0.15-0.50 Hz) or broadband HRV power spectra without any distinctive spectral peaks. Reanalysis of their ECGs showed a previously undetected intermittent atrial arrhythmia. CONCLUSIONS: Subtle arrhythmias may be difficult to detect during analyses of Holter recordings. Patients with intermittent atrial arrhythmia were identified by broadband HRV spectra and abnormal Poincaré plots. High high-frequency power in HRV and irregular heart rate patterns may indicate the presence of subtle atrial arrhythmia. Consequently, such patients should be excluded from studies of cardiac autonomic modulation.

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

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.

Reduced left atrial myocardial deformation irrespective of cavity size: a potential cause for atrial arrhythmia in hereditary transthyretin amyloidosis.

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.

Atrial fibrillation among patients under investigation for suspected obstructive sleep apnea.

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.

[Identification of paroxysmal, transient arrhythmias: Intermittent registration more efficient than the 24-hour Holter monitoring]. / Identifiering av paroxysmala, kortvariga arytmier: - Intermittent registrering mer effektiv än 24-timmars Holter-EKG.

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.

Liver transplantation does not prevent the development of life-threatening arrhythmia in familial amyloidotic polyneuropathy, Portuguese-type (ATTR Val30Met) patients.

BACKGROUND: Orthotopic liver transplantation (OLT) is today the only available treatment to halt the progress of familial amyloidotic polyneuropathy (FAP). Because heart arrhythmia and conduction disturbances are well-known manifestations of FAP, the aim of this study was to investigate the occurrence and development of heart conduction and rhythm disturbances in Swedish FAP patients who underwent liver transplantation. METHODS: Ambulatory 24-hour electrocardiography (ECG) recordings (Holter-ECGs) were available from 30 patients, who had been investigated before and reexamined after OLT. RESULTS.: The number of patients with abnormalities on their ECG recordings increased after OLT. Four patients developed serious arrhythmia after transplantation that necessitated the insertion of a pacemaker 40 months or longer after OLT. CONCLUSIONS: The development of cardiac conduction disturbances and arrhythmias appear not to be halted by liver transplantation, indicating that the physician should be aware of the potential risk for FAP patients receiving transplants to develop fatal arrhythmia. The follow-up after liver transplantation should include Holter-ECG recordings.

Holter ECG monitoring in patients with perceived electrical hypersensitivity.

Earlier studies have indicated that patients claiming to be sensitive to electromagnetic fields, so-called electrical hypersensitivity (EHS), have a dysbalance of the autonomic nervous system (ANS) regulation. This paper focuses on a possible dysbalance in the ANS among EHS patients by the use of long-term monitoring of electrocardiogram (ECG) in both a patient and a matched control group. At the same time, the environmental power frequency magnetic field was recorded for both groups in order to see if there was any difference in exposure between the groups. ECG, heart rate (HR) and heart rate variability (HRV) as well as the magnetic field exposure were monitored for 24 h. Fourteen patients with perceived EHS symptoms were selected from the University Hospital, Umeå, Sweden. Symptoms indicating autonomic nervous dysregulation were not part of the inclusion criteria of the patient group. Age and sex matched healthy subjects were used as controls. No differences were found between the groups regarding magnetic field exposure or the mean HR for 24 h. The HRV analyses showed that the high-frequency (HF) component did not have the expected increase with sleep onset and during nighttime in the EHS group. When separating the sleeping and awake time even less differences between the two conditions in the EHS patients, both for the low-frequency and HF components in the HRV spectrum, were seen. EHS patients had a disturbed pattern of circadian rhythms of HRV and showed a relatively 'flat' representation of hourly-recorded spectral power of the HF component of HRV.

Arrhythmia--a pitfall in tests of cardiac autonomic function after liver transplantation for familial amyloidotic polyneuropathy: a long-term follow-up of Swedish patients.

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.

Left ventricular dyssynchrony is associated with reduced heart rate variability in familial amyloidotic polyneuropathy.

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.

New insights into the clinical evaluation of hereditary transthyretin amyloidosis patients: a single center's experience.

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.

Comparison of quantitative sensory testing and heart rate variability in Swedish Val30Met ATTR.

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.

Blood pressure overshoot after tilt reversal in patients with familial amyloidotic polyneuropathy.

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.