Vascular aging in long-term survivors of testicular cancer more than 20 years after treatment with cisplatin-based chemotherapy.

BACKGROUND: Late effects of cisplatin-based chemotherapy in testicular cancer survivors (TCS) include cardiovascular morbidity, but little data is available beyond 20 years. The objective was to assess vascular damage in very long-term TCS. METHODS: TCS (treated with chemotherapy or orchiectomy only) and age-matched healthy controls were invited. Study assessment included vascular stiffness with ultrasound measurement of carotid-femoral pulse wave velocity (cf-PWV). RESULTS: We included 127 TCS consisting of a chemotherapy group (70 patients) and an orchiectomy group (57 patients) along with 70 controls. Median follow-up was 28 years (range: 20-42). The cf-PWV (m/s) was higher in TCS than in controls (geometrical mean 8.05 (SD 1.23) vs. 7.60 (SD 1.21), p = 0.04). The cf-PWV was higher in the chemotherapy group than in the orchiectomy group (geometrical mean 8.39 (SD 1.22) vs. 7.61 (SD 1.21), p < 0.01). In the chemotherapy group cf-PWV increased more rapidly as a function of age compared to controls (regression coefficient b 7.59 × 10-3 vs. 4.04 × 10-3; p = 0.03). CONCLUSION: Very long-term TCS treated with cisplatin-based chemotherapy show increased vascular damage compatible with "accelerated vascular aging" and continue to be at risk for cardiovascular morbidity, thus supporting the need for intensive cardiovascular risk management. CLINICAL TRIAL REGISTRATION: The clinical trial registration number is NCT02572934.

Diagnostic value of axillary artery ultrasound in patients with suspected giant cell arteritis.

OBJECTIVES: To compare colour duplex ultrasonography (CDU) findings with axillary 18F-fluorodeoxyglucose (FDG) PET/CT findings and to compare the diagnostic performance of temporal and axillary artery CDU with temporal artery CDU alone. METHODS: Patients suspected of GCA were retrospectively included. Presence of a halo or occlusion was considered a positive CDU finding. FDG-PET/CT-assessed axillary artery involvement was defined as axillary artery FDG uptake higher than liver uptake. The reference was the clinical diagnosis after 6 months, which was based on symptomatology and additional diagnostic tests, with the exception of CDU. RESULTS: Of the 113 included patients, GCA was diagnosed in 41. Twenty-eight out of 41 GCA patients underwent a FDG-PET/CT. FDG-PET-assessed extra-cranial GCA was present in 20/41 patients, of which 13 showed axillary involvement on FDG-PET/CT. An axillary halo was found in eight of these 13 patients. Six out of the 20 patients with FDG-PET-assessed GCA showed no axillary involvement on CDU or FDG-PET/CT. Five of them had single artery involvement on FDG-PET/CT (two aorta; three vertebral artery). One patient had an axillary occlusion on CDU, consistent with FDG-PET/CT results. Overall, sensitivity and specificity of temporal artery CDU was 52% (95% CI: 35, 67) and 93% (95% CI: 84, 97), respectively. Adding axillary artery results improved sensitivity to 71% (95% CI: 55, 84), while specificity did not change. CONCLUSION: Presence of an axillary halo or occlusion on CDU is consistent with axillary artery FDG-PET/CT results, but a negative CDU does not rule out axillary involvement. Adding axillary artery assessment to temporal artery assessment may substantially increase the diagnostic performance of CDU.

Treatment of resistant Raynaud's phenomenon with single-port thoracoscopic sympathicotomy: a novel minimally invasive endoscopic technique.

OBJECTIVE: To assess the minimally invasive single-port thoracoscopic sympathicotomy feasibility and efficacy in patients with treatment-resistant RP. METHODS: Single-port thoracoscopic sympathicotomy was performed unilaterally on the left side in eight patients with RP (six males, two females, with a median age of 45.2 years). Five patients had primary and three had secondary RP. Perfusion effects in the hands were assessed at baseline and after 1 month by using a cooling and recovery procedure, and by using laser speckle contrast analysis. Number and duration of RP attacks were reported over a 2-week period. RESULTS: Patient satisfaction was 100% after surgery. After surgery, a unilateral improvement in perfusion was observed in the left hand compared with the right hand, with cooling and recovery (P = 0.008) and with laser speckle contrast analysis (P = 0.023). In addition, the number and duration of the attacks in the left hand decreased compared with the right hand (both P = 0.028). No serious adverse events occurred in a follow-up period of at least 10 months. CONCLUSION: Single-port thoracoscopic sympathicotomy is feasible and can be effective in improving hand perfusion in patients with RP. However, long-term efficacy needs to be established. CLINICAL TRIAL REGISTRATION NUMBER: NCT02680509.

Vascular access creation in octogenarians: The effect of age on outcomes.

BACKGROUND: The prevalence of end-stage renal disease is accelerating among older age groups. Patient-specific factors in the elderly patient group might advocate for a different vascular access creation approach, in which patency, risk of nonmaturation, and time to cannulation with accompanied prolonged catheter use should be of primary importance. The aim of this study was to determine which vascular access has the best outcomes and to determine whether age is associated with different outcomes after vascular access surgery. METHODS: Data were obtained from a prospectively maintained database of patients treated between November 2004 and December 2017. Two different patient groups were identified: the octogenarian group, consisting of patients aged ≥80 years; and the control group, consisting of all the other patients. A total of 694 vascular access procedures were included in this study, 65 in the octogenarian group and 629 in the control group. Primary, primary assisted, and secondary patency rates were calculated and compared between groups and vascular accesses. Multivariable analysis was used to determine whether age is an effect modifier in the association between type of vascular access and different patency outcomes. RESULTS: Mean follow-up was 23.2 months in the octogenarian group and 21.2 months in the control group (P = .210). No significant differences were found in patient survival, with a 5-year survival rate of 63.8% (±5.9%) in the octogenarian group and 57.2% (±2.2%) in the control group (P = .866). Within the octogenarian group, primary failure rate was highest in the radiocephalic arteriovenous fistula (AVF) patients, 42.1% (P = .006). Brachiocephalic AVF had significantly improved assisted patency compared with the other vascular accesses among the octogenarians (P = .016). Age was not an effect modifier in the association between type of vascular access and different patency outcomes. The adjusted analysis, corrected for octogenarian age, diabetes mellitus, hypertension, and sex, showed that brachiocephalic AVF was significantly associated with an increase in primary patency (hazard ratio, 0.70; 95% confidence interval, 0.54-0.90; P = .006) and primary assisted patency (hazard ratio, 0.58; 95% confidence interval, 0.39-0.86; P = .006) compared with other vascular accesses. CONCLUSIONS: The results of our study support primary placement of a brachiocephalic AVF in the octogenarian patient. A low primary failure rate was achieved with significant improved patency rates compared with the other vascular accesses.

Outcomes after endovascular mechanical thrombectomy in occluded vascular access used for dialysis purposes.

PURPOSE: Endovascular mechanical thrombectomy using the AngioJet™ system can be considered to reestablish patency in occluded vascular access. The aim of this study was to review our results for endovascular mechanical thrombectomy using the AngioJet™ system in patients with arteriovenous fistulae (AVF) and arteriovenous grafts (AVG). METHODS: Data collected in a database of patients requiring hemodialysis for renal failure were analyzed. Patients who underwent endovascular mechanical thrombectomy procedures with the AngioJet™ system for occlusion of vascular access were included. Clinical and technical success rates and patency rates were calculated. Multivariate analysis was used to identify factors of influence. RESULTS: A total of 92 AngioJet™ procedures in 60 patients with thrombosed vascular access were reviewed during a mean follow-up period of 21.5 months in patients with an AVF and 11.9 months in patients with an AVG. Technical and clinical success was achieved in 92.6% of AVF cases and 92.0 and 90.8% of AVG cases with an AVG, respectively. Significantly higher primary and primary-assisted patency rates were observed in the AVF group. Multivariate regression analysis indicated that left-sided vascular access and female sex were independent predictors for failure regarding primary patency in AVG patients. Immunosuppressive drugs and older age were negative predictors for secondary patency in AVG patients. CONCLUSIONS: The AngioJet™ system can be deemed an effective technique to reestablish patency in occluded vascular access with minimal use of central venous catheters for dialysis. Good technical and clinical success rates were achieved with acceptable patency rates, especially in AVF patients.

Higher Anxiety Is Associated with Lower Cardiovascular Autonomic Function in Female Twins.

Anxiety symptoms co-occur with cardiovascular health problems, with increasing evidence suggesting the role of autonomic dysfunction. Yet, there is limited behavior genetic research on underlying mechanisms. In this twin study, we investigated the phenotypic, genetic and environmental associations between a latent anxiety factor and three cardiovascular autonomic function factors: interbeat interval (IBI, time between heart beats), heart rate variability (HRV, overall fluctuation of heart-beat intervals) and baroreflex sensitivity (BRS, efficiency in regulating blood pressure [BP]). Multivariate twin models were fit using data of female twins (N = 250) of the Twin Interdisciplinary Neuroticism Study (TWINS). A significant negative association was identified between latent anxiety and BRS factors (r = -.24, 95% CI [-.40, -.07]). Findings suggest that this relationship was mostly explained by correlated shared environmental influences, and there was no evidence for pleiotropic genetic or unique environmental effects. We also identified negative relationships between anxiety symptoms and HRV (r = -.17, 95% CI [-.34, .00]) and IBI factors (r = -.13, 95% CI [-.29, .04]), though these associations did not reach statistical significance. Findings implicate that higher anxiety scores are associated with decreased efficiency in short-term BP regulation, providing support for autonomic dysfunction with anxiety symptomatology. The baroreflex system may be a key mechanism underlying the anxiety-cardiovascular health relationship.

Outcomes of basilic vein transposition versus polytetrafluoroethylene forearm loop graft as tertiary vascular access.

BACKGROUND: Radial-cephalic arteriovenous fistula and brachial-cephalic arteriovenous fistula are the first and second choices for creating vascular access in dialysis patients as recommended by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Basilic vein transposition or use of a forearm (polytetrafluoroethylene [PTFE]) loop graft is recommended thereafter. The aim of this study was twofold: first, to compare the outcomes and patency rates of patients treated with a basilic vein transposition with those of patients treated with a PTFE loop; and second, to identify patient-related factors of influence on patency rates. METHODS: Data collected in our prospectively maintained database of patients with chronic renal dysfunction requiring hemodialysis were analyzed. From April 2006 to August 2017, there were 55 patients with a basilic vein transposition and 75 patients with a PTFE loop included. Primary, primary assisted, and secondary patency rates were calculated. Multivariate analysis was used to identify factors of influence on survival. Incidence rates of complications and reinterventions were calculated and compared. RESULTS: Mean follow-up time was 29 months. A significantly higher 2-year primary assisted patency rate was found for the basilic vein transposition group (72.7% ± 6.5% vs 47.6% ± 6.2%; P < .01). The 2-year primary patency rates and secondary patency rates were comparable between basilic vein transposition and PTFE loop (25.1% ± 6.6% vs 13.7% ± 4.4% [P = .11] and 75.5% ± 6.5% vs 73.9% ± 5.3% [P = .17], respectively). Cox regression identified body mass index (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.05-2.98; P = .03) and age (HR, 0.54; 95% CI, 0.32-0.91; P = .02) as predictors for failure regarding primary patency in PTFE loop patients. Previous catheter use (HR, 0.29; 95% CI, 0.12-0.70; P = .006) and the presence of diabetes (HR, 3.32; 95% CI, 1.50-7.39; P = .003) were independent predictors for failure regarding primary patency in basilic vein transposition patients. The incidence rate of total complications was significantly higher in the PTFE loop group with 0.70 per patient-year (PY-1) compared with 0.28 PY-1 in the basilic vein transposition group (P = .001). In terms of intervention rate, a significantly higher percutaneous transluminal angioplasty rate and surgical revision rate were found in the PTFE loop group than in the basilic vein transposition group (1.77 PY-1 vs 1.05 PY-1 [P = .022] and 0.20 PY-1 vs 0.07 PY-1 [P = .002], respectively). CONCLUSIONS: In this nonrandomized study, basilic vein transposition has better primary assisted patency, fewer complications, and fewer reinterventions compared with PTFE loop.

Heart Rate Variability and Its Relation to Chronic Kidney Disease: Results From the PREVEND Study.

OBJECTIVE: In the general population, reduced heart rate variability (HRV) has been associated with cardiovascular disease. However, its relation to chronic kidney disease (CKD) is debated. We therefore investigated the relation between low HRV and renal outcomes. METHODS: In the population-based Prevention of REnal and Vascular ENdstage Disease study, renal outcomes (CKD, estimated glomerular filtration rate [eGFR], urinary albumin) were measured at baseline and three consecutive examinations. HRV measures (among which SDNN [standard deviation of normal-to-normal RR intervals]) were calculated from time series of beat-to-beat pulse wave recordings at baseline. The lowest (risk) quartile was compared with the upper three quartiles combined, in multivariable survival and linear mixed-effects analyses. RESULTS: In 4605 participants (49% males, age range = 33-80, 0.6% blacks), we observed 341 new participants of CKD during a median follow-up duration of 7.4 years. Low SDNN was associated with higher incidence of CKD (crude HR = 1.66, 95% CI = 1.30 to 2.12, p < .001), but this association was no longer significant after adjustment for age, sex, and cardiovascular risk factors (adjusted HR = 1.13, 95% CI = 0.86 to 1.48, p = .40, similar for other HRV measures). No associations between SDNN and eGFR trajectories were found in the total sample. However, in a subgroup of participants with baseline CKD (n = 939), we found a significant association of low SDNN (but not other HRV measures) with lower baseline eGFR, even after multivariable adjustment (adjusted ßlevel difference = -3.73 ml/min/1.73 m, 95% CI = -6.70 to -0.75, p = .014), but not with steeper eGFR decline. CONCLUSIONS: These results suggest that reduced HRV may be a complication of CKD rather than a causal factor.

Long-term cardiovascular outcome of renal transplant recipients after early conversion to everolimus compared to calcineurin inhibition: results from the randomized controlled MECANO trial.

Long-term data on cardiovascular (CV) outcome of renal transplant recipients (RTR) on mTOR-i (mammalian Target Of Rapamycin-inhibitors) are scarce. In a sub-study of the MECANO trial we investigated changes in intima media thickness (IMT), CV risk profile, Major Adverse CV Events (MACE) and survival in RTR on a mTORi versus CNI based regimen. Patients (enrolled 361) were treated with (basiliximab) and triple IS (CsA-Cyclosporine A-(C), MPS (M), prednisolone (P)). At M6 patients were randomized (n = 224) to the CsA group (C, P, N = 89), MPS group (M, P, N = 39) EVL group (Everolimus, P, N = 96). At week 2, M6 and M 24, IMT measurements of the Common Carotid Artery were performed. Cardiovascular risk factors were assessed at baseline, 6 and 24 months of follow-up. Seven years survival and MACE-free survival probability were calculated by the Cardiovascular Risk Calculator for RTR. After 7 years of follow-up, incidence of cardiovascular events and patient survival were assessed. Mean IMT at baseline (N = 192), was 0.64 ± 0.14 mm. At M6 (N = 158), 0.66 ± 0.15, M24 IMT was 0.68 ± 0.15 (N = 95). No significant differences between groups concerning IMT, true CV events and mortality, CV risk profile, predicted MACE/Mortality were found between mTORi and CNI-based regimen after 7 years of follow-up.

Effect of plasma sodium concentration on blood pressure regulators during hemodialysis: a randomized crossover study.

BACKGROUND: Intradialytic hypotension is a common complication of hemodialysis. The Hemocontrol biofeedback system, improving intradialytic hemodynamic stability, is associated with an initial transient increase in plasma sodium levels. Increases in sodium could affect blood pressure regulators. METHODS: We investigated whether Hemocontrol dialysis affects vasopressin and copeptin levels, endothelial function, and sympathetic activity in twenty-nine chronic hemodialysis patients. Each patient underwent one standard hemodialysis and one Hemocontrol hemodialysis. Plasma sodium, osmolality, nitrite and nitrate (NOx), endothelin-1, angiopoietins-1 and 2, and methemoglobin as measures of endothelial function, plasma catecholamines as indices of sympathetic activity and plasma vasopressin and copeptin levels were measured six times during each modality. Blood pressure, heart rate, blood volume, and heart rate variability were repeatedly monitored. Generalized Estimating Equations was used to compare the course of the parameters during the two treatment modalities. RESULTS: Plasma sodium and osmolality were significantly higher during the first two hours of Hemocontrol hemodialysis. Overall, mean arterial pressure (MAP) was higher during Hemocontrol dialysis. Neither the measures of endothelial function and sympathetic activity nor copeptin levels differed between the two dialysis modalities. In contrast, plasma vasopressin levels were significantly higher during the first half of Hemocontrol dialysis. The intradialytic course of vasopressin was associated with the course of MAP. CONCLUSIONS: A transient intradialytic increase in plasma sodium did not affect indices of endothelial function or sympathetic activity compared with standard hemodialysis, but coincided with higher plasma vasopressin levels. The beneficial effect of higher intradialytic sodium levels on hemodynamic stability might be mediated by vasopressin. TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT03578510 . Date of registration: July 5th, 2018. Retrospectively registered.

Orthostatic blood pressure recovery patterns in suspected syncope in the emergency department.

INTRODUCTION: Orthostasis is a frequent trigger for (pre)syncope but some forms of orthostatic (pre)syncope have a worse prognosis than others. Routine assessment of orthostatic BP in the ED can detect classic orthostatic hypotension, but often misses these other forms of orthostatic (pre)syncope. This study aimed to determine the frequency of abnormal orthostatic BP recovery patterns in patients with (pre)syncope by using continuous non-invasive BP monitoring. METHODS: We performed a prospective cohort study in suspected patients with (pre)syncope in the ED of a tertiary care teaching hospital between January and August 2014. Orthostatic BP was measured during the active lying-to-standing test with Nexfin, a continuous non-invasive finger arterial pressure measurement device. Orthostatic BP recovery patterns were defined as normal BP recovery, initial orthostatic hypotension, delayed BP recovery, classic orthostatic hypotension and reflex-mediated hypotension. RESULTS: Of 116 patients recruited, measurements in 111 patients (age 63 years, 51% male) were suitable for analysis. Classic orthostatic hypotension was the most prevalent abnormal BP pattern (19%), but only half of the patients received a final diagnosis of orthostatic hypotension. Initial orthostatic hypotension and delayed BP recovery were present in 20% of the patients with (pre)syncope of whom 45% were diagnosed as unexplained syncope. Reflex-mediated hypotension was present in 4% of the patients. CONCLUSION: Continuous non-invasive BP measurement can potentially identify more specific and concerning causes of orthostatic (pre)syncope. Correct classification is important because of different short-term and long-term clinical implications.

Effect of linagliptin on pulse wave velocity in early type 2 diabetes: A randomized, double-blind, controlled 26-week trial (RELEASE).

AIMS: To evaluate the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin on aortic pulse wave velocity (PWV) as a surrogate marker of arterial stiffness and early atherosclerosis in people with early type 2 diabetes. METHODS: A total of 45 people with type 2 diabetes (median [interquartile range] age 63 [54-66] years, 61% men, mean ± standard deviation glycated haemoglobin [HbA1c] 6.3% ± 0.4% [45 ± 4.6 mmol/mol]), without cardiovascular disease and naïve to antidiabetic treatment, were randomized (1:1) to treatment with linagliptin 5 mg once daily or placebo for 26 weeks in a double-blind fashion. PWV was assessed at baseline, 4 and 26 weeks of treatment, and again at 30, 4 weeks after treatment. The primary endpoint was between-group difference in PWV (corrected for systolic blood pressure [SBP]) at week 26. Secondary endpoints included differences in central SBP and augmentation index (AIx). RESULTS: Compared with placebo, 26 weeks of linagliptin decreased PWV by an average of 0.91 m/s (95% confidence interval -1.76 to -0.06; P = .035). PWV returned to baseline after 4 weeks washout. Differences in central SBP and AIx were not different between linagliptin and placebo. Linagliptin decreased HbA1c (-0.4%; P < .001), fasting plasma glucose (-0.7 mmol/L; P = .002) and triglycerides (-0.49 mmol/L; P = .019) as compared with placebo. The changes in body weight, cholesterol and high-sensitivity C-reactive protein did not differ between groups. CONCLUSIONS: Linagliptin decreased aortic PWV in people with early-stage type 2 diabetes as compared with placebo after 26 weeks of treatment. These results suggest that linagliptin has a favourable effect on arterial stiffness.

Digital ischaemia during cooling is independently related to nailfold capillaroscopic pattern in patients with Raynaud's phenomenon.

OBJECTIVE: The aim of the study was to assess the association between plethysmographically measured vasospasms during stepwise cooling and recovery, as an index for digital ischaemia, and nailfold capillaroscopic pattern (NCP) severity in patients with primary or secondary RP, including SSc. METHODS: In 381 consecutive patients with suspected RP without a history of digital ulcers, NCP (assessed by widefield videocapillaroscopy), fingertip photoelectric plethysmography during cooling and recovery and clinical characteristics were analysed. NCPs were graded as follows: normal, non-specific, early and active. The mean ischaemic time was defined as the mean time of perfusion loss during cooling and recovery of five fingers. RESULTS: In the patients with loss of perfusion during cooling and recovery, the NCP was normal in 152, non-specific in 96, early in 61 and active in 39 patients. The mean ischaemic time was positively associated with the severity of NCP, with P < 0.05 for each two- or three-grade increase and independent of underlying SSc. The difference was most pronounced during recovery. CONCLUSION: We demonstrate that the degree of vasospasm and ischaemia provoked by stepwise cooling and recovery are positively associated with NCP in patients with RP of different aetiologies and without a history of digital ulcers.

Change in telomere length and cardiovascular risk factors in testicular cancer survivors.

BACKGROUND: Testicular cancer (TC) survivors cured with chemotherapy (CT) are prone to develop cardiovascular diseases, as part of an accelerated aging phenotype. A mechanism contributing to these events can be telomere shortening. PATIENTS AND METHODS: In a prospective cohort of patients with disseminated TC who received cisplatin-based CT, mean absolute leukocyte telomere length (TL) was measured before and 1 year after start of treatment. Cardiovascular risk factors, including development of the metabolic syndrome and hypogonadism, were assessed before and up to 5 years after CT. RESULTS: For the whole group (n = 55), TL did not change 1 year after CT (5.7 (2.2-13.4) vs. 5.8 kb (1.6-19.2), P = 0.335). At baseline, patients with a BMI >30 kg/m2 (n = 12) had shorter TL (4.9 (2.2-13.4) vs. 6.3 kb (3.1-12.9), P = 0.045), while no age-dependent differences were measured. Patients with TL shortening after 1 year (n = 7) showed a significant increase in diastolic blood pressure (P = 0.007) and triglycerides (P = 0.003), compared to those with unchanged TL. There was no association between telomere shortening after 1 year or short TL at baseline (n = 7+11) and development of metabolic syndrome (25% vs. 21%; P = 0.777), or hypogonadism (38% vs. 17%; P = 0.120) after 5 years. CONCLUSIONS: A small subset of TC patients treated with cisplatin-based CT showed telomere shortening 1 year after treatment. This shortening was associated to a rise in diastolic blood pressure and triglycerides, but not to newly developed metabolic syndrome and hypogonadism after 5 years.

Heart rate variability parameters do not correlate with pain intensity in healthy volunteers.

OBJECTIVE: When patients cannot indicate pain, physiological parameters may be useful. We tested whether heart rate variability (HRV) parameters, as reflection of sympathetic and vagal tone, can be used to quantify pain intensity. DESIGN: Prospective study. SUBJECTS AND SETTING: A standardized heat stimulus was applied to the forearm in 75 healthy volunteers during three study periods of 2 minutes. METHODS: Before and after each application, pain intensity was measured by a visual analog scale (VAS) and inter beat interval (IBI) was recorded. Standard deviation of normal to normal beat intervals (SDNN) of the IBI, the power of the low (LF, 0.07-0.14 Hz) and high frequency (HF, 0.15-0.50 Hz) band, and LF/HF ratio were calculated. Log transformation resulted in normal distribution. Correlation between HRV parameters and pain intensity was assessed by Pearson's correlation coefficient. RESULTS: Data from 73 volunteers (44 women) could be analyzed. The mean age was 30 ± 11 years. Compared with baseline, during all heat periods, pain intensity measured by VAS increased from 2 ± 3 mm, 3 ± 5 mm, and 2 ± 4 mm, to 40 ± 20 mm, 42 ± 21 mm, and 44 ± 22 mm, respectively. Log transformed SDNN (lnSDNN) and LF (lnLF) decreased; lnSDNN from 4.0 ± 0.4 to 3.9 ± 0.5, P = 0.002; 4.0 ± 0.4 to 3.9 ± 0.5, P = 0.016; and 4.1 ± 0.4 to 3.9 ± 0.4, P = 0.004, respectively; lnLF from 6.3 ± 1.0 to 6.1 ± 1.2, P = 0.001; 6.4 ± 1.0 to 6.2 ± 1.1, P = 0.019; and 6.5 ± 1.0 to 6.2 ± 1.1, P = 0.020, respectively. No correlation of any HRV parameter with VAS score was found. CONCLUSION: HRV parameters may detect responses to heat pain, but are not suitable to assess pain intensity.

Predicting recurrence of depression using cardiac complexity in individuals tapering antidepressants.

It is currently unknown whether the complexity and variability of cardiac dynamics predicts future depression and whether within-subject change herein precedes the recurrence of depression. We tested this in an innovative repeated single-subject study in individuals who had a history of depression and were tapering their antidepressants. In 50 individuals, electrocardiogram (ECG) derived Interbeat-interval (IBI) time-series data were collected for 5 min every morning and evening, for 4 months. Usable data were obtained from 14 participants who experienced a transition (i.e., a clinically significant increase in depressive symptoms) and 14 who did not. The mean, standard deviation, Higuchi dimension and multiscale entropy, calculated from IBIs, were examined for time trends. These quantifiers were also averaged over a baseline period and compared between the groups. No consistent trends were observed in any quantifier before increases in depressive symptoms within individuals. The entropy baseline levels significantly differed between the two groups (morning: P value < 0.001, Cohen's d = -2.185; evening: P value < 0.001, Cohen's d = -1.797) and predicted the recurrence of depressive symptoms, in the current sample. Moreover, higher mean IBIs and Higuchi dimensions were observed in individuals who experienced transitions. While we found little evidence to support the existence of within- individual warning signals in IBI time-series data preceding an upcoming depressive transition, our results indicate that individuals who taper antidepressants and showed lower entropy of cardiac dynamics exhibited a higher chance of recurrence of depression. Hence, entropy could be a potential digital phenotype for assessing the risk of recurrence of depression in the short term while tapering antidepressants.

Similar outcomes of arteriovenous fistulae created under general or regional anesthesia.

BACKGROUND: There is growing evidence that type of anesthesia can significantly change vascular access surgery outcomes. Still, there is limited evidence on the impact of regional anesthesia (RA) on patency and failure rates compared to general anesthesia (GA). The aim of this study was to compare the outcomes of RA and GA in patients who underwent vascular access creation at our center. METHODS: Data collected in our prospectively maintained database of patients with chronic renal dysfunction requiring hemodialysis were analyzed, 464 patients were included. Outcome parameters such as maturation, primary failure, postoperative flow measurements, patency rates, and survival outcomes were compared between RA and GA groups. RESULTS: In this study 489 vascular access procedures were performed in 464 patients, 318 included in the RA group and 171 in the GA group. Median follow-up time was 29.9 (IQR 37.3) months in the RA group versus 33.0 (IQR 40.7) in the GA group (p = 0.252). Anesthesia type did not significantly affect patient survival (HR, 1.01; CI, 0.70-1.45; p = 0.976). No significant differences were found in vascular access flow volume, primary failure, or time to cannulation between the RA and GA groups for both radiocephalic arteriovenous fistulae and brachiocephalic arteriovenous fistulae. Anesthesia type did not significantly change patency outcomes. CONCLUSIONS: Based on our results, both RA and GA demonstrate similar results regarding patient survival, maturation, failure, or patency after vascular access creation. Still, patient-specific factors for each type of anesthesia as well as patient preference should be considered.

Observational and genetic evidence support a relationship between cardiac autonomic function and blood pressure.

Background: It is unclear how cardiac autonomic function, as indicated by heart rate (HR), heart rate variability (HRV), HR increase during exercise, and HR recovery after exercise, is related to blood pressure (BP). We aimed to examine the observational and genetic evidence for a potential causal effect of these HR(V) traits on BP. Methods: We performed multivariable adjusted linear regression using Lifelines and UK Biobank cohorts to investigate the relationship between HR(V) traits and BP. Linkage disequilibrium score regression was conducted to examine genetic correlations. We used two-sample Mendelian randomization (2SMR) to examine potential causal relations between HR(V) traits and BP. Results: Observational analyses showed negative associations of all HR(V) traits with BP, except for HR, which was positively associated. Genetic correlations were directionally consistent with the observational associations, but most significant genetic correlations between HR(V) traits and BP were limited to diastolic blood pressure (DBP). 2SMR analyses suggested a potentially causal relationship between HR(V) traits and DBP but not systolic blood pressure (SBP). No reverse effect of BP on HR(V) traits was found. One standard deviation (SD) unit increase in HR was associated with a 1.82 mmHg elevation of DBP. In contrast, one ln(ms) unit increase of the root mean square of the successive differences (RMSSD) and corrected RMSSD (RMSSDc), decreased DBP by 1.79 and 1.83 mmHg, respectively. For HR increase and HR recovery at 50 s, every additional SD increase was associated with a lower DBP by 2.05 and 1.47 mmHg, respectively. Results of secondary analyses with pulse pressure as outcome were inconsistent between observational and 2SMR analyses, as well as between HR(V) traits, and therefore inconclusive. Conclusion: Both observational and genetic evidence show strong associations between indices of cardiac autonomic function and DBP, suggesting that a larger relative contribution of the sympathetic versus the parasympathetic nervous system to cardiac function may cause elevated DBP.

Phenotypic but not genetically predicted heart rate variability associated with all-cause mortality.

Low heart rate variability (HRV) has been widely reported as a predictor for increased mortality. However, the molecular mechanisms are poorly understood. Therefore, this study aimed to identify novel genetic loci associated with HRV and assess the association of phenotypic HRV and genetically predicted HRV with mortality. In a GWAS of 46,075 European ancestry individuals from UK biobank, we identified 17 independent genome-wide significant genetic variants in 16 loci associated with HRV traits. Notably, eight of these loci (RNF220, GNB4, LINCR-002, KLHL3/HNRNPA0, CHRM2, KCNJ5, MED13L, and C160rf72) have not been reported previously. In a prospective phenotypic relationship between HRV and mortality during a median follow-up of seven years, individuals with lower HRV had higher risk of dying from any cause. Genetically predicted HRV, as determined by the genetic risk scores, was not associated with mortality. To the best of our knowledge, the findings provide novel biological insights into the mechanisms underlying HRV. These results also underline the role of the cardiac autonomic nervous system, as indexed by HRV, in predicting mortality.

Ultrasound for the Detection of Inflammatory Abdominal Aortic Aneurysms: A Case and Validation Series.

Inflammatory abdominal aortic aneurysms (iAAA) are a form of noninfectious aortitis in patients with abdominal aortic aneurysms (AAA). Ultrasound could help to detect iAAA early. This retrospective observational study assessed the potential of using ultrasound to detect iAAA in a case series of iAAA patients, and the diagnostic value of ultrasound to detect iAAA in consecutive patients in a follow-up for AAA, referred to as a feasibility study. In both studies, diagnosis of iAAA was based on a cuff surrounding the aneurysm using CT (golden standard). The case series included 13 patients (age 64 (61; 72) years; 100% male). The feasibility study included 157 patients (age 75 (67; 80) years; 84% male). In the case series, all iAAA patients showed a cuff surrounding the aortic wall on ultrasound. In the feasibility study with AAA patients, ultrasound yielded no cuff in 147 (93.6%; CT negative in all cases), a typic cuff in 8 (5.1%; CT positive in all cases), and an inconclusive cuff in 2 (1.3%; CT negative in both cases) patients. Sensitivity and specificity were 100% and 98.7%, respectively. This study indicates that iAAA can be identified with ultrasound, and safely ruled out. In positive ultrasound cases, additional CT imaging might still be warranted.