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Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an infiltrative disease of the myocardium in which extracellular deposits of amyloid cause progressive cardiac impairment.

Objectives: We aimed to evaluate left atrial (LA) deformation and its association with left ventricular (LV) deformation using LA-LV strain loops in patients with ATTR-CM and patients with left ventricular hypertrophy (LVH). We hypothesized that LA strain in ATTR-CM patients is abnormal and more independent of LV strain, compared to LVH patients.

Methods: Retrospective study based on echocardiographic data including 30 patients diagnosed with ATTR-CM based on an end diastolic interventricular septal (IVSd) thickness of ≥14mm, and 29 patients with LVH (IVSd ≥14mm and no ATTR-CM diagnosis) together with 30 controls. LV global longitudinal strain (LV-GLS) and LA strain, assessed as peak atrial longitudinal strain (PALS), were acquired and plotted to construct LA-LV strain loops and using regression line to determine a LA-LV strain slope.

Results: Significantly lower PALS and LA-LV strain slope values were detected in ATTR-CM patients compared to LVH patients (p=0.004 and p=0.014 respectively). A ROC curve demonstrated similar area under the curve (AUC) using PALS (AUC 0.72) and LA-LV slope (AUC 0.71), with both resulting in higher values than recorded for LV-GLS (AUC 0.62).

Conclusions: LA deformation demonstrates an independent ability to differentiate ATTR-CM from LVH. Combining LV strain and LA deformation analysis displays the mechanical LA/LV dissociation in ATTR-CA and potentially unmasks LA amyloid infiltration, this could potentially enable quicker diagnosis and initiation of treatment for ATTR-CM.

Objective: Previous research points to a role of the brain in the regulation of glucose and pathogenesis of type 2 diabetes (T2D) via modulation of counter-regulatory hormone secretion and activity in the autonomic nervous system (ANS). The aim of this study was to investigate glucose-dependent responses of catecholamines and ANS activity in individuals with T2D, prediabetes (PD), and normoglycemia (NG).

Design: Cross-sectional.

Methods: Individuals with T2D (n = 19, 7 men, HbA1c 49 mmol/mol), PD (n = 18, 8 men), and NG (n = 17, 3 men) underwent 1 stepwise hyperinsulinemic-euglycemic-hypoglycemic and 1 hyperglycemic clamp with repeated measurements of catecholamines, symptoms, heart rate variability (HRV), and hemodynamics.

Results: The hypoglycemic response of adrenaline was augmented in T2D and PD vs NG (both P <. 05), and there was a strong association with insulin resistance (P <. 05 for M-value). In relation to achieved glucose levels in both clamps, noradrenaline exhibited a steeper rise during hypoglycemia in T2D vs NG and PD (both P <. 05). There were trends toward more marked autonomic hypoglycemic symptoms in T2D vs PD and NG. By contrast, insulin resistance was associated with attenuated responses of heart rate and HRV indices P_LF and P_HF at the target glucose plateau of 2.7 mmol/L (P <. 05), independent of BMI and HbA1c.

Conclusion: Alterations in glucose-dependent responses of counter-regulatory hormones and the ANS appear before, and probably contribute to, the onset of T2D. Together with other reported alterations in neuroendocrine pathways, the findings suggest that a maladaptation of the brain's responses to glucose fluctuations is important in T2D progression.

Objectives: This study aimed to retrospectively assess cardiac autonomic activity in children with LQTS, considering genotype, symptoms, sex, age, and beta-blocker therapy (BB) and compare it to healthy controls.

Methods: Heart rate variability (HRV), using power spectrum analysis, was analyzed in 575 Holter recordings from 116 children with LQTS and in 69 healthy children. The data were categorized into four age-groups and four heart rate (HR) ranges.

Results: In LQT1 and LQT2, increasing HR corresponded to significantly lower low (LF) and high frequency (HF) compared to controls. Total power (PTOT) was lower in all LQT1 age-groups compared to controls at HR 120–140 bpm (1–15 years: p <.01; 15–18 years: p =.03). At HR 80–100, LQT1 patients aged 1–10 years had lower HF than LQT2 patients (1–5 years: p =.05; 5–10 years: p =.02), and LQT2 patients aged 15–18 years had lower HF than LQT1 patients (p <.01). Symptomatic patients aged 10–15 years had lower PTOT at HR 100–120 bpm than asymptomatic patients (p =.04). LQT1 girls aged 10–15 and 15–18 years had a lower PTOT (10–15 years: p =.04; 15–18 years: p =.02) than boys.

Conclusion: This study shows a correlation between HR and changes in HRV parameters. At higher HRs, LQTS patients generally had lower HRV values than controls, suggesting an abnormal autonomic response. These results may strengthen the link between physical activity and arrhythmias in LQTS.

Background: The assessment of left ventricular (LV) filling pressure in heart failure (HF) poses a diagnostic challenge, as HF patients may have normal LV filling pressures at rest but often display elevated LV filling pressures during exercise. Rapid preload increase during passive leg lift (PLL) may unmask HF in such challenging scenarios. We explored the dynamic interplay between simultaneous left atrial (LA) function and volume using LA strain/volume loops during rest and PLL and compared its diagnostic performance with conventional echocardiographic surrogates to detect elevated LV filling pressure.

Methods: We retrospectively reviewed 35 patients with clinical HF who underwent simultaneous echocardiography and right heart catheterization before and immediately after PLL. Patients with atrial fibrillation (n = 4) were excluded. Twenty age-matched, healthy controls were added as controls. LA reservoir strain (LASr) was analyzed using speckle-tracking echocardiography. LA strain–volume loops were generated, including the best-fit linear regression line employing simultaneous LASr and LA volume.

Results: LA strain–volume slope was lower for HF patients when compared with controls (0.71 vs. 1.22%/mL, p < 0.001). During PLL, the LA strain–volume slope displayed a moderately strong negative correlation with invasive pulmonary arterial wedge pressure (PAWP) (r = −0.71, p < 0.001). At a 0.74%/mL cut-off, the LA strain–volume slope displayed 88% sensitivity and 86% specificity to identify elevated PAWP (AUC 0.89 [0.76–1.00]). In comparison, LASr demonstrated strong but numerically lower diagnostic performance (AUC 0.82 [0.67–0.98]), and mitral E/e’ showed poor performance (AUC 0.57 [0.32–0.82]).

Conclusions: In this proof-of-concept study, LA strain–volume characteristics provide incremental diagnostic value over conventional echocardiographic measures in the identification of elevated LV filling pressure.

BACKGROUND: Swimming is a genotype-specific trigger in long QT syndrome type 1 (LQT1).

OBJECTIVE: To examine the autonomic response to water activities in children and adolescents with LQT1.

METHODS: In this cross-sectional study, LQT1 patients were age and sex matched to one healthy control subject. Electrocardiograms (ECGs) were recorded during face immersion (FI), swimming, diving, and whole-body submersion (WBS). Heart rate (HR) and heart rate variability (HRV) was measured. The high frequency (HF) component of HRV was interpreted to reflect parasympathetic activity, while the low frequency (LF) component was interpreted as reflecting the combined influence of sympathetic and parasympathetic activity on autonomic nervous modulation of the heart.

RESULTS: Fifteen LQT1 patients (aged 7-19 years, all on beta-blocker therapy) and fifteen age and sex matched non-medicated controls were included. No significant ventricular arrhythmias were observed in the LQT1 population during the water activities. Out of these 15 matched pairs, 12 pairs managed to complete FI and WBS for more than 10 seconds and were subsequently included in HR and HRV analyses. In response to FI, the LQT1 group experienced a drop in HR of 48 bpm, compared to 67 bpm in the control group (p = 0.006). In response to WBS, HR decreased by 48 bpm in the LQT1 group and 70 bpm in the control group (p = 0.007). A significantly lower PTOT (p < 0.001) and HF (p = 0.011) component was observed before, during and after FI in LQT1 patients compared with the controls. Before, during and after WBS, a significantly lower total power (p < 0.001), LF (p = 0.002) and HF (p = 0.006) component was observed in the LQT1 patients.

CONCLUSION: A significantly lower HR decrease in response to water activities was observed in LQT1 subjects on beta-blocker therapy, compared to matched non-medicated controls. The data suggests an impaired parasympathetic response in LQT1 children and adolescents. An aberrant autonomic nervous system (ANS) response may cause an autonomic imbalance in this patient group.

Background: It is established that the risk of cardiovascular disease (CVD) is increased in patients with Rheumatoid Arthritis (RA). Heart rate variability (HRV) is a method for evaluating the activity in the cardiac autonomic nervous system. Our aim was to assess the longitudinal development of HRV in patients with RA and compare with healthy controls. Furthermore, we wanted to investigate associations between HRV, inflammatory disease activity and cardiovascular complications in patients with RA over time.

Method: HRV was assessed with frequency-domain analysis at baseline and after five years in 50 patients with early RA, all being younger than 60 years. HRV indices were age-adjusted based on the estimated age-dependency in 100 age and sex matched healthy controls. Additionally, clinical data including serological markers, disease activity, and blood pressure were collected from the patients. Eleven years after inclusion CVD was assessed.

Results: At baseline, patients with RA presented with lower HRV compared to controls during deep breathing (6 breaths/min), paced normal breathing (12 breaths/min) and after passive tilt to the upright position. No significant change in HRV was observed at the five-year follow-up. A significant negative correlation was found between HRV parameters and systolic blood pressure (SBP) at baseline. A significant positive correlation was found between heart rate and inflammatory markers at baseline but not after five years. Nine patients had developed CVD after 11 years, but no significant association was found with baseline HRV data.

Conclusion: This study showed that patients with RA have autonomic imbalance both at an early stage of the disease and after five years, despite anti-rheumatic medication, but no correlation between HRV and inflammation markers were observed. Reduced HRV was also significantly negatively correlated with increased SBP. Hypertension is a common finding in patients with RA. Thus, significant decline of HRV could be a useful early marker for development of hypertension in patients with RA.

Background: An association between impaired exercise capacity and risk of mortality has been reported among adults with congenital heart disease (CHD). Over the years, treatment methods have improved and may influence outcome. Hence, we report data from a national cohort reflecting a contemporary population.

Objectives: The purpose of this study was to investigate the association between exercise capacity (workload) and mortality in a large registry-based cohort.

Methods: Data on exercise capacity using cycle ergometer were retrieved from the national registry of CHD. The association between predicted exercise capacity (%ECpred) and mortality was analyzed using Cox regression.

Results: In total, 3,721 adults (>18 years, 44.6% women) with CHD were included. The median age was 27.0 years (IQR: 20.8-41.0 years) and mean %ECpred was 77% ± 20%. Over a mean follow-up of 9.4 ± 6.0 years, there were 214 (5.8%) deaths. The Multivariable Cox regression model showed that moderately and severely impaired exercise capacity (50-<70 %ECpred: HR: 2.1, 95% CI: 1.4-3.2, P < 0.001, and <50 %ECpred: HR: 3.5, 95% CI: 2.1-6.0, P < 0.001) and CHD complexity were associated with higher mortality (moderate complexity: HR: 1.9 95% CI: 1.2-3.0, P = 0.003, great complexity: HR: 2.3 95% CI: 1.3-4.2, P = 0.008) when adjusted for New York Heart Association class, physical activity, cardiovascular medication, sex, impaired systemic ventricular function, and age.

Conclusions: Impaired exercise capacity and CHD complexity are independently associated with all-cause mortality in patients with CHD. Exercise capacity is an easily accessible variable that may be a useful tool for risk assessment in adult patients with CHD, but this needs confirmation in prospective studies.

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.

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.

The use of implantable cardioverter defibrillators (ICDs) in long QT syndrome (LQTS) patients is essential in high-risk patients. However, it is sometimes used in patients without high-risk profiles for whom the expected benefit may be lower than the risk of ICD harm. Here, we evaluated ICD benefit and harm by assessing risk according to risk scores and pre-ICD clinical characteristics. Design. We studied 109 Swedish LQTS patients drawn from the Swedish ICD and Pacemaker Registry with data collected from medical records. In addition to clinical characteristics, we used two risk scores to assess pre-ICD risk, and evaluated ICD benefit and harm. Results. Twenty percent of all patients received ≥1 appropriate shock with a first appropriate shock incidence rate of 4.3 per 100 person-years. A long QTc (≥550 ms) and double mutations were significantly associated with appropriate shock. Low risk scores among patients without pre-ICD aborted cardiac arrest were not significantly associated with low risk of first appropriate shock. The incidence rates of a first inappropriate shock and first complication were 3.0 and 7.6 per 100 person-years, respectively. Conclusion. Our findings on ICD harm emphasize the importance of careful individual pre-ICD consideration. When we applied two risk scores to patients without pre-ICD aborted cardiac arrest, we could not validate their ability to identify patients with low risk of appropriate shocks and patients who were assessed as having a low risk still received appropriate shocks. This further supports the complexity of risk stratification and the difficulty of using risk scores.