Rolf Hörnsten

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.

Heart complications in familial transthyretin amyloidosis: impact of age and gender.

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.

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.

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. Liver Transpl 17:122–128, 2011.

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

BackgroundMany 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.MethodsDesign: 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).Results95 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.ConclusionsIntermittent 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.

Cardiac autonomic function does not improve after liver transplantation for familial amyloidotic polyneuropathy

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.

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

BackgroundUndetected 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 ResultsTwenty-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.ConclusionsThe 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.

Outcome of heart rate variability and ventricular late potentials after liver transplantation for familial amyloidotic polyneuropathy

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.

Heart Rate Variability in Children with Fontan Circulation

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.

Gastric emptying in hereditary transthyretin amyloidosis: the impact of autonomic neuropathy

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.