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Objective: Prediction of specific cardiovascular outcomes may facilitate precision medicine in hypertension. We aimed to explore risk factor heterogeneity for acute coronary syndrome (ACS), stroke and heart failure in treatment-eligible hypertensive patients.

Methods: In this population-based cohort study in Västerbotten, Sweden, middle-aged patients with treatment-eligible hypertension were included. Association between traditional cardiovascular risk factors and ACS, stroke and heart failure was studied. Multinomial logistic regression was performed to determine standardized odds ratios.

Results: Over a 10-year period, there were 1190 cardiovascular events in 12 238 participants. Risk factor associations were mainly of the same direction but differed in magnitude across cardiovascular outcomes. Total cholesterol was significantly associated with ACS, but not with heart failure and stroke. Smoking and male sex were more strongly associated with ACS than with heart failure and stroke. BMI and socioeconomic factors were significantly associated with heart failure, but not with ACS and stroke. Diabetes and DBP had stronger associations with stroke compared to ACS and heart failure.

Conclusion: We found clinically important differences in the association between different risk factors and ACS, stroke and heart failure in treatment-eligible hypertensive patients. The current model was insufficient to guide treatment decisions but should stimulate further research into risk factor heterogeneity between cardiovascular disease outcomes.

As cold-water immersion becomes more popular and accessible, it is important to explore potential risks. This study examines the cardiac autonomic response and arrhythmia occurrence in healthy adolescents during face and body immersion. Healthy ninth-grade students, aged 15–16 years, were recruited to perform face immersion (FI) in 10°C water and body immersion in 2°C water (IWI). Electrocardiograms (ECGs) were continuously recorded, and the heart rate (HR) response and occurrence of arrhythmias were assessed. Among the 54 individuals performing FI, six had supraventricular extrasystoles, and two had ventricular bigeminy. Among the 20 performing IWI, four had supraventricular extrasystoles. The HR response was more pronounced during FI compared to IWI (p < 0.001). During both FI and IWI, girls showed initially higher HR and more pronounced HR reduction than boys, but there were no significant sex differences (p = 0.26). During the first 30 seconds of IWI, boys maintained a steady HR (p = 0.176), while girls experienced a near-linear reduction (p = 0.009). This study indicates a low risk of severe arrhythmias when briefly immersing the body in ice-cold water in healthy adolescents. However, the risk could increase if combined with face submersion and apnea.

Purpose: The aim of this study was to assess the effects of acute Glucagon-like peptide-1 (GLP-1) receptor agonist administration on metabolic and endocrine responses to a standardized meal test in individuals who have undergone Roux-en-Y gastric bypass surgery (RYGB), and thus to uncover mechanisms that might be important in post-bariatric hypoglycemia.

Methods: In a single-center, randomized crossover study, 10 patients without diabetes underwent two standardized high-carbohydrate meal tests with either saline (SAL) or exenatide (EXE) infusion, one year after RYGB. We assessed glucose, insulin, c-peptide, ACTH, cortisol, GH, adrenalin, noradrenalin, dopamine, glucagon, active GLP-1 and GIP. Gastric emptying rate was estimated with repeated paracetamol measurements. Heart rate variability was recorded as a marker of sympathetic nervous system activity.

Results: Postprandial glucose levels dropped below baseline levels in all subjects. Cortisol levels were higher during EXE infusion. As expected, insulin and c-peptide levels were higher with EXE. No other significant differences were observed in the measured hormones. EXE did not affect gastric emptying rate. HRV showed a decreased RR-interval during EXE infusion.

Conclusion: During a meal test, acute exenatide infusion led to elevated cortisol levels but did not protect against post-prandial drops in glucose levels. Taken together with previous research, this implicates that alleviation of post-prandial hypoglycemia after RYGB via GLP-1 receptor agonist treatment likely involves other mechanisms than acute effects on conventional counter-regulatory hormones.

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.