Our initial experience of monitoring the autoregulation of cerebral blood flow during cardiopulmonary bypass.

BACKGROUND: Cerebral blood flow (CBF) is believed to be relatively constant within an upper and lower blood pressure limit. Different methods are available to monitor CBF autoregulation during surgery. This study aims to critically analyze the application of the cerebral oxygenation index (COx), one of the commonly used techniques, using a reference to data from a series of clinical registrations. METHOD: CBF was monitored using near-infrared spectroscopy, while cerebral blood pressure was estimated by recordings obtained from either the radial or femoral artery in 10 patients undergoing cardiopulmonary bypass. The association between CBF and blood pressure was calculated as a moving continuous correlation coefficient. A COx index > 0.4 was regarded as a sign of abnormal cerebral autoregulation (CA). Recordings were examined to discuss reliability measures and clinical feasibility of the measurements, followed by interpretation of individual results, identification of possible pitfalls, and suggestions of alternative methods. RESULTS AND CONCLUSION: Monitoring of CA during cardiopulmonary bypass is intriguing and complex. A series of challenges and limitations should be considered before introducing this method into clinical practice.

Pulmonary function in a cohort of heart-healthy individuals from Northern Sweden-a comparison with discordant reference values.

BACKGROUND: Dynamic spirometry is an important investigation to differentiate between impaired and normal lung function. This study aimed to evaluate the results of lung function testing in a cohort of subjects from Northern Sweden without any known heart or pulmonary disease. Our focus was to compare with two reference materials that have showed differences in the age-dependency of lung function in Swedish subjects. METHODS: The study population consisted of 285 healthy adults (148 males, 52%) between 20-90 years of age. The subjects had been randomly selected from the population register for inclusion in a study investigating cardiac function in heart-healthy subjects, but were also assessed with dynamic spirometry. At least seven percent reported smoking. Sixteen subjects presented with pulmonary functional impairments and were excluded from the current study. The sex-specific age-dependency in lung volumes was estimated using the LMS model, where non-linear equations were derived for the mean value (M), the location (L) or skewness, and the scatter (S) or coefficient of variation. This model of the observed lung function data was compared with reference values given by the original LMS model published by the Global Lung Initiative (GLI), and with the model from the recent Obstructive Lung Disease In Norrbotten (OLIN) study, where higher reference values were presented for Swedish subjects than those given by the GLI model. RESULTS: No differences were found in the age-dependency of pulmonary function between the LMS model developed in the study and the OLIN model. Although the study group included smokers, the original GLI reference values suggested significantly lower normal values of FEV1 (forced expiratory volume) and FVC (forced vital capacity), and consequently fewer subjects below the lower limit of normality, than both the rederived LMS and OLIN models. CONCLUSIONS: Our results are in line with previous reports and support that the original GLI reference values underestimate pulmonary function in the adult Swedish population. This underestimation could be reduced by updating the coefficients in the underlying LMS model based on a larger cohort of Swedish citizens than was available in this study.

Time Course of Metabolic, Neuroendocrine, and Adipose Effects During 2 Years of Follow-up After Gastric Bypass in Patients With Type 2 Diabetes.

CONTEXT: Roux-en-Y gastric bypass surgery (RYGB) markedly improves glycemia in patients with type 2 diabetes (T2D), but underlying mechanisms and changes over time are incompletely understood. OBJECTIVE: Integrated assessment of neuroendocrine and metabolic changes over time in T2D patients undergoing RYGB. DESIGN AND SETTING: Follow-up of single-center randomized study. PATIENTS: Thirteen patients with obesity and T2D compared to 22 healthy subjects. INTERVENTIONS: Blood chemistry, adipose biopsies, and heart rate variability were obtained before and 4, 24, and 104 weeks post-RYGB. RESULTS: After RYGB, glucose-lowering drugs were discontinued and hemoglobin A1c fell from mean 55 to 41 mmol/mol by 104 weeks (P < 0.001). At 4 weeks, morning cortisol (P < 0.05) and adrenocorticotropin (P = 0.09) were reduced by 20%. Parasympathetic nerve activity (heart rate variability derived) increased at 4 weeks (P < 0.05) and peaked at 24 weeks (P < 0.01). C-reactive protein (CRP) and white blood cells were rapidly reduced (P < 0.01). At 104 weeks, basal and insulin-stimulated adipocyte glucose uptake increased by 3-fold vs baseline and expression of genes involved in glucose transport, fatty acid oxidation, and adipogenesis was upregulated (P < 0.01). Adipocyte volume was reduced by 4 weeks and more markedly at 104 weeks, by about 40% vs baseline (P < 0.01). CONCLUSIONS: We propose this order of events: (1) rapid glucose lowering (days); (2) attenuated cortisol axis activity and inflammation and increased parasympathetic tone (weeks); and (3) body fat and weight loss, increased adipose glucose uptake, and whole-body insulin sensitivity (months-years; similar to healthy controls). Thus, neuroendocrine pathways can partly mediate early glycemic improvement after RYGB, and adipose factors may promote long-term insulin sensitivity and normoglycemia.

Changes in Heart Rate and Heart Rate Variability During Surgical Stages to Completed Fontan Circulation.

Arrhythmia is related to heart rate variability (HRV), which reflects the autonomic nervous regulation of the heart. We hypothesized that autonomic nervous ganglia, located at the junction of the superior vena cava's entrance to the heart, may be affected during the bidirectional Glenn procedure (BDG), resulting in reduced HRV. We aimed to investigate changes in heart rate and HRV in a cohort of children with univentricular heart defects, undergoing stepwise surgery towards total cavopulmonary connection (TCPC), and compare these results with healthy controls. Twenty four hours Holter-ECG recordings were obtained before BDG (n = 47), after BDG (n = 47), and after total cavopulmonary connection (TCPC) (n = 45) in patients and in 38 healthy controls. HRV was analyzed by spectral and Poincaré methods. Age-related z scores were calculated and compared using linear mixed effects modeling. Total HRV was significantly lower in patients before BDG when compared to healthy controls. The mean heart rate was significantly reduced in patients after BDG compared to before BDG. Compared to healthy controls, patients operated with BDG had significantly reduced heart rate and reduced total HRV. Patients with TCPC showed reduced heart rate and HRV compared with healthy controls. In patients after TCPC, total HRV was decreased compared to before TCPC. Heart rate was reduced after BDG procedure, and further reductions of HRV were seen post-TCPC. Our results indicate that autonomic regulation of cardiac rhythm is affected both after BDG and again after TCPC. This may be reflected as, and contribute to, postoperative arrhythmic events.

Effects of Gastric Bypass Surgery on the Brain: Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia.

While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by 18F-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.

Refeeding syndrome: multimodal monitoring and clinical manifestation of an internal severe neurotrauma.

Refeeding syndrome (RFS) is a rare, potentially life-threatening, condition seen in malnourished patients starting refeeding. RFS may provoke seizures and acute encephalopathy and can be considered an internal severe neurotrauma in need of specific treatment. The objective was to describe course of disease, treatment and, for the first time, multimodal monitoring output in a comatose patient suffering RFS. After gastric-banding and severe weight loss, the patient initiated self-starving and was transferred to our intensive care unit (ICU) following rapid refeeding. At arrival, seizures, decrease in consciousness (GCS 7) and suspected acute encephalitis was presented. Serum albumin was 8 g/l. Intracranial pressure (ICP), invasive blood pressure and electrocardiography (ECG) were monitored. Pressure reactivity (PRx) and compliance (RAP) were calculated. The patient developed congestive heart failure, anuria and general oedema despite maximal neuro- and general ICU treatment. Global cerebral oedema and hypoperfusion areas with established ischemia were seen. ECG revealed massive cardiac arrhythmia and disturbed autonomic regulation. PRx indicated intact autoregulation (-0.06 ± 0.18, mean ± SD) and relatively normal compliance (RAP = 0.23 ± 0.13). After 15 days the clinical state was improved, and the patient returned to the primary hospital. RFS was associated with serious deviations in homeostasis, high ICP levels, ECG abnormalities, kidney and lung affections. It is of utmost importance to recognize this rare syndrome and to treat appropriately. Despite the severe clinical state, cerebral autoregulation and compensatory reserve were generally normal, questioning the applicability of indirect measurements such as PRx and RAP during neuro-intensive care treatment of RFS patients with cerebral engagement.

Rapid changes in neuroendocrine regulation may contribute to reversal of type 2 diabetes after gastric bypass surgery.

OBJECTIVE: To explore the role of hormones and the autonomic nervous system in the rapid remission of diabetes after Roux-en-Y Gastric Bypass (RYGB). RESEARCH DESIGN AND METHODS: Nineteen obese patients with type 2 diabetes, 7 M/12 F, were randomized (2:1) to RYGB or standard-of-care medical treatment (control). At baseline and 4 and 24 weeks post surgery, fasting blood sampling, OGTT, intravenous arginine challenge, and heart-rate variability (HRV) assessments were performed. RESULTS: At both 4 and 24 weeks post-RYGB the following effects were found: arginine-stimulated insulin secretion was reduced. GLP-1, GIP, and glucagon rise during OGTT was enhanced. IGF-1 and GH levels increased. In addition, total HRV and spectral components PLF (power of low frequency) and PHF (power of high frequency) increased. At 4 weeks, morning cortisol was lower than baseline and 24 weeks. At 24 weeks, NEFA levels during OGTT, and the PLF/PHF ratio decreased. None of these changes were seen in the control group. CONCLUSIONS: There were rapid changes within 4 weeks after RYGB: signs of enhanced parasympathetic nerve activity, reduced morning cortisol, and enhanced incretin and glucagon responses to glucose. The findings suggest that neurohormonal mechanisms can contribute to the rapid improvement of insulin resistance and glycemia following RYGB in type 2 diabetes.

Effects of GLP-1 on counter-regulatory responses during hypoglycemia after GBP surgery.

OBJECTIVES: The aim of the study was to explore the role of GLP-1 receptor activation on the counter-regulation and symptoms of hypoglycemia in subjects who have undergone gastric bypass surgery (GBP). DESIGN: Experimental hyperinsulinemic-hypoglycemic clamp study. METHODS: Twelve post-GBP subjects participated in a randomized cross-over study with two hyperinsulinemic, hypoglycemic clamps (glucose nadir 2.7 mmol/L) performed on separate days with concomitant infusions of the GLP-1 analog exenatide or with saline, respectively. Continuous measurements of metabolites and counter-regulatory hormones as well as assessments of heart rate variability and symptoms of hypoglycemia were performed throughout the clamps. RESULTS: No effect of GLP-1 receptor activation on counter-regulatory hormones (glucagon, catecholamines, cortisol, GH) or glucose infusion rate was seen, but we found indications of a downregulation of the sympathetic relative to the parasympathetic nerve activity, as reflected in heart rate variability. No significant differences in symptom of hypoglycemia were observed. CONCLUSIONS/INTERPRETATION: Short-term exposure to a GLP-1 receptor agonist does not seem to impact the counter-regulatory hormonal and metabolic responses in post-GBP subjects during hypoglycemic conditions, suggesting that the improvement in symptomatic hypoglycemia post-GBP seen following treatment with GLP-1 receptor agonists may be mediated by mechanism not directly involved in counter-regulation.

Pacemaker treatment after Fontan surgery-A Swedish national study.

OBJECTIVE: Fontan surgery is performed in children with univentricular heart defects. Previous data regarding permanent pacemaker implantation frequency and indications in Fontan patients are limited and conflicting. We examined the prevalence of and risk factors for pacemaker treatment in a consecutive national cohort of patients after Fontan surgery in Sweden. METHODS: We retrospectively reviewed all Swedish patients who underwent Fontan surgery from 1982 to 2017 (n = 599). RESULTS: After a mean follow-up of 12.2 years, 13% (78/599) of the patients with Fontan circulation had received pacemakers. Patients operated with the extracardiac conduit (EC) type of total cavopulmonary connection had a significantly lower prevalence of pacemaker implantation (6%) than patients with lateral tunnel (LT; 17%). Mortality did not differ between patients with (8%) and without pacemaker (5%). The most common pacemaker indication was sinus node dysfunction (SND) (64%). Pacemaker implantation due to SND was less common among patients with EC. Pacemaker implantation was significantly more common in patients with mitral atresia (MA; 44%), double outlet right ventricle (DORV; 24%) and double inlet left ventricle (DILV; 20%). In contrast, patients with pulmonary atresia with intact ventricular septum and hypoplastic left heart syndrome were significantly less likely to receive a pacemaker (3% and 6%, respectively). CONCLUSIONS: Thirteen percent of Fontan patients received a permanent pacemaker, most frequently due to SND. EC was associated with a significantly lower prevalence of pacemaker than LT. Permanent pacemaker was more common in patients with MA, DORV, and DILV.

Sinus node dysfunction in patients with Fontan circulation: could heart rate variability be a predictor for pacemaker implantation?

Sinus node dysfunction (SND) causes significant morbidity in patients after Fontan surgery. Heart rate variability (HRV) reflects the autonomic regulation of the heart, and changes in HRV have been associated with SND in adults. We aimed to study whether changes in HRV could be detected in 24-h electrocardiographic (ECG) recordings in Fontan patients with SND. We compared HRV results from two patient groups; patients with Fontan circulation who later required a pacemaker due to severe SND (n = 12) and patients with Fontan circulation and SND, without indication for pacemaker treatment (n = 11), with two control groups; patients with Fontan circulation without SND (n = 90) and healthy controls (n = 66). The Poincaré plot index SD2 (representing changes in heart rate over 24-h) and the very low-frequency (VLF) HRV component were significantly higher in both SND groups, both compared with healthy controls and patients with Fontan circulation without SND. In SND patients with pacemakers, SD2 and VLF were slightly reduced compared to SND patients without pacemaker (p = 0.06). In conclusion, in Fontan patients with SND the HRV is significantly higher compared to healthy controls and Fontan patients without SND. However, in patients with severe SND requiring pacemaker, SD2 and VLF tended to be lower than in patients with SND without pacemaker, which could indicate a reduced diurnal HRV in addition to the severe bradycardia. This is a small study, but our results indicate that HRV analysis might be a useful method in the follow-up of Fontan patients regarding development of SND.

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.

Diabetes and male sex are key risk factor correlates of the extent of coronary artery calcification: A Euro-CCAD study.

BACKGROUND AND AIMS: Although much has been written about the conventional cardiovascular risk factor correlates of the extent of coronary artery calcification (CAC), few studies have been carried out on symptomatic patients. This paper assesses the potential ability of risk factors to associate with an increasing CAC score. METHODS: From the European Calcific Coronary Artery Disease (Euro-CCAD) cohort, we retrospectively investigated 6309 symptomatic patients, 62% male, from Denmark, France, Germany, Italy, Spain and the USA. All had conventional cardiovascular risk factor assessment and CT scanning for CAC scoring. RESULTS: Among all patients, male sex (OR = 4.85, p<0.001) and diabetes (OR = 2.36, p<0.001) were the most important risk factors of CAC extent, with age, hypertension, dyslipidemia and smoking also showing a relationship. Among patients with CAC, age, diabetes, hypertension and dyslipidemia were associated with an increasing CAC score in males and females, with diabetes being the strongest dichotomous risk factor (p<0.001 for both). These results were echoed in quantile regression, where diabetes was consistently the most important correlate with CAC extent in every quantile in both males and females. To a lesser extent, hypertension and dyslipidemia were also associated in the high CAC quantiles and the low CAC quantiles respectively. CONCLUSION: In addition to age and male sex in the total population, diabetes is the most important correlate of CAC extent in both sexes.

Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia.

Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.

Can echocardiography and ECG discriminate hereditary transthyretin V30M amyloidosis from hypertrophic cardiomyopathy?

OBJECTIVE: Hereditary transthyretin (ATTR) amyloidosis with increased left ventricular wall thickness could easily be misdiagnosed by echocardiography as hypertrophic cardiomyopathy (HCM). Our aim was to create a diagnostic tool based on echocardiography and ECG that could optimise identification of ATTR amyloidosis. METHODS: Data were analysed from 33 patients with biopsy proven ATTR amyloidosis and 30 patients with diagnosed HCM. Conventional features from ECG were acquired as well as two dimensional and Doppler echocardiography, speckle tracking derived strain and tissue characterisation analysis. Classification trees were used to select the most important variables for differentiation between ATTR amyloidosis and HCM. RESULTS: The best classification was obtained using both ECG and echocardiographic features, where a QRS voltage >30 mm was diagnostic for HCM, whereas in patients with QRS voltage <30 mm, an interventricular septal/posterior wall thickness ratio (IVSt/PWt) >1.6 was consistent with HCM and a ratio <1.6 supported the diagnosis of ATTR amyloidosis. This classification presented both high sensitivity (0.939) and specificity (0.833). CONCLUSION: Our study proposes an easily interpretable classification method for the differentiation between HCM and increased left ventricular myocardial thickness due to ATTR amyloidosis. Our combined echocardiographic and ECG model could increase the ability to identify ATTR cardiac amyloidosis in clinical practice.

Touch massage: a pilot study of a complex intervention.

OBJECTIVES: To report and evaluate a complex touch massage intervention according to the British Medical Research Council framework. This study aimed to evaluate the effects of touch massage on levels of anxiety and physiological stress in patients scheduled for elective aortic surgery. BACKGROUND: The use of touch massage has increased during the past decade but no systematic studies have been implemented to investigate the effectiveness of such treatment. It is important to conduct multidisciplinary investigations into the effects of complex interventions such as touch massage. For this, the British Medical Research Council has provided a useful framework to guide the development, piloting, evaluation and reporting of complex intervention studies. METHOD: A pilot study with a randomized controlled design including 20 patients (10 + 10) scheduled for elective aortic surgery. Selected outcome parameters included; self-reported anxiety, measured by the State-Trait Anxiety Inventory Form Y instrument, and physiological stress, measured by heart rate variability, blood pressure, respiratory frequency, oxygen saturation and concentrations of cortisol, insulin and glucose in serum. RESULTS: There were significant differences in self-reported anxiety levels before and after touch massage (p = 0.007), this was not observed in the control group (p = 0.833). There was a significant difference in self-reported anxiety levels between the touch massage group and the control group after touch massage and rest (p = 0.001). There were no significant differences in physiological stress-related outcome parameters between patients who received touch massage and controls. CONCLUSION: In our study, touch massage decreased anxiety levels in patients scheduled for elective aortic surgery, and the British Medical Research Council framework was a useful guideline for the development, evaluation and reporting of a touch massage intervention. RELEVANCE TO CLINICAL PRACTICE: Touch massage can reduce patients' anxiety levels and is thus an important nursing intervention in intensive and post-operative care.

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.

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.

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.