Update on advanced interventional neuromodulatory approaches to lower blood pressure.

Herein, we review interventional peripheral neuromodulatory approaches to reduce blood pressure (BP), specifically focusing on catheter-based renal denervation (RDN), as well as the latest data from recent clinical trials underpinning its clinical use. Given the apparent failure of established lifestyle measures and pharmacologic BP-lowering approaches to improve hypertension (HTN) control rates, the past decade has seen remarkable scientific efforts to explore the utility of interventional strategies for BP management. Experimental studies and human clinical trials have demonstrated the crucial role of the sympathetic nervous system in the development and mainenance of HTN - consequently, most recent interventional technologies aimed primarily at modulating neural pathways. Advanced approaches that were rigorously tested in human studies include RDN, endovascular baroreflex amplification, baroreflex activation therapy and cardiac neuromodulation stimulation.Amongst these, RDN is by far the most established technology. With recent robust evidence from clinical trials and real-world data showing the safety and efficacy of both ultrasound and radiofrequency-based approaches, a recent clinical consensus statement of the European Society of Cardiology Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions concludes that RDN represents an ancillary therapeutic option in patients with uncontrolled resistant HTN confirmed by ambulatory blood pressure measurement and in spite of attention to lifestyle changes and optimised pharmacological treatment. Furthermore, RDN could alos be considered for patienst unlikley to adhere to or tolerate long-term antihypertensive drug treatment. Very recent data indicate long-term safety and efficacy up to 10 years. Appropriate implementation of RDN into clinical practice is now warranted.For all other interventions additional data from adequately designed human studies are required to establish their safety and clinical utility for potential future use in routine practice.

Multi-organ denervation: a novel approach to combat cardiometabolic disease.

Cardiometabolic disorders are associated with a substantial loss in quality of life and pose a large burden on healthcare systems worldwide. Overactivation of the sympathetic nervous system has been shown to be a key player in several aspects relating to cardiometabolic disturbances. While diet- and exercise-induced approaches to help reduce weight remains the main strategy to combat metabolic disorders, this is often difficult to achieve. Current pharmacological approaches result in variable responses in different patient cohorts and long-term efficacy may be limited by medication side effects and non-adherence in the long term. There is a clear clinical need for complementary therapies to curb the burden of cardiometabolic disease. One such approach may include interventional sympathetic neuromodulation of organs relevant to cardiometabolic control. Data from sham-controlled clinical trials demonstrate the feasibility, safety and efficacy of catheter-based renal denervation. In analogy, denervation of the common hepatic artery is now feasible in humans and may prove to be similarly useful in modulating sympathetic overdrive directed towards the liver, pancreas and duodenum. Such a targeted multi-organ neuromodulation strategy may beneficially influence multiple aspects of the cardiometabolic disease continuum including blood pressure, glucose and lipid control.

Evolving Role of Catheter Ablation for Atrial Fibrillation: Early and Effective Rhythm Control.

Catheter Ablation (CA) is an effective therapeutic option in treating atrial fibrillation (AF). Importantly, recent data show that CA as a rhythm control strategy not only significantly reduces AF burden, but also substantially improves clinical hard endpoints. Since AF is a progressive disease, the time of Diagnosis-to-Intervention appears crucial. Recent evidence shows that earlier rhythm control is associated with a lower risk of adverse cardiovascular outcomes in patients with early AF. Particularly, CA as an initial first line rhythm control strategy is associated with significant reduction of arrhythmia recurrence and rehospitalization in patients with paroxysmal AF. CA is shown to significantly lower the risk of progression from paroxysmal AF to persistent AF. When treating persistent AF, the overall clinical success after ablation remains unsatisfactory, however the ablation outcome in patients with "early" persistent AF appears better than those with "late" persistent AF. "Adjunctive" ablation on top of pulmonary vein isolation (PVI), e.g., ablation of atrial low voltage area, left atrial posterior wall, vein of Marshall, left atrial appendage, etc., may further reduce arrhythmia recurrence in selected patient group. New ablation concepts or new ablation technologies have been developing to optimize therapeutic effects or safety profile and may ultimately improve the clinical outcome.

Adjunctive Left Atrial Posterior Wall Isolation in Treating Atrial Fibrillation: Insight From a Large Secondary Analysis.

OBJECTIVES: This study evaluated the role of adjunctive left atrium posterior wall isolation (PWI) in preventing atrial fibrillation (AF) recurrence. BACKGROUND: The left atrium posterior wall is an arrhythmogenic substrate that contributes to the development of AF. METHODS: This was an updated pooled analysis that included clinical data regarding PWI plus pulmonary vein isolation (PVI) in treating AF. The primary outcome was recurrence of atrial tachyarrhythmias. RESULTS: A total of 26 studies with 3,287 patients with AF (age 61.7 ± 10.8 years) were included. Mean follow-up was 15.2 ± 8.4 months. Procedural success to achieve PWI was 92.8%. In paroxysmal AF, adjunctive PWI did not reduce the recurrence of all atrial arrhythmias (P = 0.21) or AF (P = 0.37); however, in persistent AF, adjunctive PWI was associated with substantially lower recurrence of all atrial arrhythmias (risk ratio: 0.74; P < 0.001) and AF (risk ratio: 0.67; P = 0.01), particularly when randomized data were included. Subgroup analyses based on meta-regression demonstrated that patients with older age, a larger left atrial diameter, and persistent AF benefited more significantly from the adjunctive PWI. Adjunctive PWI using either radiofrequency or a cryoballoon reduced AF recurrence, whereas using radiofrequency seemed to be associated with higher recurrence rate of atrial tachycardias and/or atrial flutter. Non-BOX adjunctive PWI rather than BOX PWI was associated with significantly lower recurrence of AF. The incidence of procedural adverse events between the PVI+PWI (3.2%) and PVI (2.8%) groups was low and similar. PVI+PWI needed longer ablation and/or procedural time but had similar fluoroscopy time. CONCLUSIONS: Adjunctive PWI can be achieved in most patients without compromising safety. Patients with persistent AF appear to benefit from this approach. The ablation technology and/or approach may affect the clinical outcome of PWI.

Retinal Capillary Damage Is Already Evident in Patients With Hypertension and Prediabetes and Associated With HbA1c Levels in the Nondiabetic Range.

OBJECTIVE: We analyzed whether any change in capillary density in the retinal circulation could be detected in patients with hypertension in the prediabetic stage. RESEARCH DESIGN AND METHODS: In a cross-sectional analysis, we assessed capillary density in the foveal (CDF) and parafoveal retinal areas using optical coherence tomography-angiography in 62 patients with hypertension and normal glucose metabolism and 40 patients with hypertension and prediabetes. RESULTS: The CDF was lower in patients with prediabetes than in those with normal glucose metabolism. Moreover, we found a correlation between CDF and HbA1c and glucose levels for the entire cohort. In patients with HbA1c <6.5% (48 mmol/mol), CDF was lower in patients with HOMA for insulin resistance (HOMA-IR) ≥2.5 than in patients with HOMA-IR <2.5. CONCLUSIONS: Patients with hypertension and prediabetes display retinal capillary changes, and an association with markers of glucose metabolism exists, even within a nondiabetic HbA1c range.

Autoencoded deep features for semi-automatic, weakly supervised physiological signal labelling.

BACKGROUND AND AIMS: Machine Learning is transforming data processing in medical research and clinical practice. Missing data labels are a common limitation to training Machine Learning models. To overcome missing labels in a large dataset of microneurography recordings, a novel autoencoder based semi-supervised, iterative group-labelling methodology was developed. METHODS: Autoencoders were systematically optimised to extract features from a dataset of 478621 signal excerpts from human microneurography recordings. Selected features were clusters with k-means and randomly selected representations of the corresponding original signals labelled as valid or non-valid muscle sympathetic nerve activity (MSNA) bursts in an iterative, purifying procedure by an expert rater. A deep neural network was trained based on the fully labelled dataset. RESULTS: Three autoencoders, two based on fully connected neural networks and one based on convolutional neural network, were chosen for feature learning. Iterative clustering followed by labelling of complete clusters resulted in all 478621 signal peak excerpts being labelled as valid or non-valid within 13 iterations. Neural networks trained with the labelled dataset achieved, in a cross validation step with a testing dataset not included in training, on average 93.13% accuracy and 91% area under the receiver operating curve (AUC ROC). DISCUSSION: The described labelling procedure enabled efficient labelling of a large dataset of physiological signal based on expert ratings. The procedure based on autoencoders may be broadly applicable to a wide range of datasets without labels that require expert input and may be utilised for Machine Learning applications if weak-labels were available.

Anticoagulation in atrial fibrillation and liver disease: a pooled-analysis of >20 000 patients.

AIMS: Anticoagulation for atrial fibrillation patients with liver disease represents a clinical dilemma. We sought to evaluate the efficacy/safety of different anticoagulation, i.e. vitamin K antagonist (VKA) and non-VKA oral anticoagulants (NOACs) in such patient group. METHODS AND RESULTS: This was a pooled-analysis enrolling up-to-date clinical data. Two subsets: subset A (VKA vs. Non-Anticoagulation) and subset B (NOACs vs. VKA) were pre-specified. The study outcomes were ischaemic stroke (IS)/thromboembolism (TE), major bleeding (MB), intracranial bleeding (ICB), gastrointestinal bleeding (GIB), and all-cause mortality. A total of 20 042 patients' data were analysed (subset A: N = 10 275, subset B: N = 9767). Overall mean age: 71 ± 11 years, mean CHA2DS2-VASc score: 4.0 ± 1.8, mean HAS-BLED score: 3.6 ± 1.2. The majority of the patients had Child-Pugh category (A-B). As compared with Non-Anticoagulation, VKA seemed to reduce the risk of IS/TE [odds ratio (OR): 0.60, P = 0.05], but heighten the risk of all-bleeding events including MB (OR: 2.81, P = 0.01), ICB (OR: 1.60, P = 0.01), and GIB (OR: 3.32, P = 0.01). When compared with VKA, NOACs had similar efficacy in reducing the risk of IS/TE (OR: 0.82, P = 0.64), significantly lower risk of MB (OR: 0.54, P = 0.0003) and ICB (OR: 0.35, P < 0.0001), and trend towards reduced risk of GIB (OR: 0.72, P = 0.12) and all-cause mortality (OR: 0.79, P = 0.35). The favourable effects were maintained in subgroups of individual NOAC. CONCLUSIONS: VKA appears to reduce the risk of IS/TE but increase all-bleeding events. NOACs have similar effect in reducing the risk of IS/TE and have significantly lower risk of MB and ICB as compared with VKA. NOACs seem to be associated with better clinical outcome than VKA in patients with mild-moderate liver disease.

Simultaneously measured inter-arm blood pressure difference is not associated with pulse wave velocity in a clinical dataset of at-risk hypertensive patients.

Recent analysis of systolic inter-arm differences in blood pressure from the INTERPRESS-IPD Collaboration suggest an association with increased all-cause mortality, cardiovascular mortality and cardiovascular events. Previous studies have demonstrated associations with other risk parameters. We aimed to reproduce these associations in a cohort of 199 treated, at-risk hypertensive patients with pulse wave velocity (PWV) as a surrogate marker of cardiovascular (CV) damage. Simultaneously measured inter-arm blood pressure (BP) differences, 24 hour ambulatory BP and PWV were measured in 199 treated patients from a tertiary hospital hypertension outpatient clinic. Associations between systolic inter-arm BP difference and PWV were analyzed with uni- and multi-variate regression models. Out of 199 participants, 90 showed an inter-arm BP difference of more than 5 mmHg. The inter-arm difference was not associated with PWV. Furthermore, neither observed single BP measurements nor 24 hour ambulatory BP was associated with inter-arm BP differences. In our clinical patient cohort we failed to observe an association between inter-arm BP differences and PWV. Mode of assessment, study design and the sample characteristics of this treated, hypertensive cohort may have contributed to the negative findings. The limited sample size of the study poses a challenge to the detection of smaller effects in our study.

Renal denervation alters ambulatory blood pressure-derived salt sensitivity index in patients with uncontrolled hypertension.

BACKGROUND: Renal denervation (RDN) has been proven in multiple sham-controlled trials to lower blood pressure (BP) in various forms of hypertension. RDN-mediated interruption of sympathetic signaling through its effects on renal blood flow, salt retention, and renin release are likely contributors to the BP-lowering effects. However, the impact of RDN on salt sensitivity in humans has not yet been explored. METHODS: We, therefore, investigated the effect of RDN on ambulatory BP monitoring-derived salt sensitivity in a cohort of patients with uncontrolled hypertension on habitual salt intake. RDN was performed in 153 hypertensive patients, who were categorized into low intermediate and high-salt sensitivity groups, based on the ambulatory BP monitoring-derived salt sensitivity index estimated prior to (baseline) and at 3, 6 and 12 months after the procedure as previously described. Crude and adjusted mixed effects ordinal regression models were fitted to test for changes in the proportions of salt sensitivity risk during follow-up. RESULTS: The proportions of individuals in the intermediate and high-salt sensitivity risk group increased after RDN and the odds for being in a higher estimated salt sensitivity risk group at 3, 6 and 12 months follow-up compared with baseline were highly significant during the 12 months follow-up period. CONCLUSION: Increased salt sensitivity after RDN may represent a compensatory mechanism to maintain renal capacity for adequate salt handling. This novel finding may have implications for patient management after RDN, such as prescription of salt moderation to further optimize RDN-induced BP-lowering efficacy.

K-means panning - Developing a new standard in automated MSNA signal recognition with a weakly supervised learning approach.

BACKGROUND: Accessibility of labelled datasets is often a key limitation for the application of Machine Learning in clinical research. A novel semi-automated weak-labelling approach based on unsupervised clustering was developed to classify a large dataset of microneurography signals and subsequently used to train a Neural Network to reproduce the labelling process. METHODS: Clusters of microneurography signals were created with k-means and then labelled in terms of the validity of the signals contained in each cluster. Only purely positive or negative clusters were labelled, whereas clusters with mixed content were passed on to the next iteration of the algorithm to undergo another cycle of unsupervised clustering and labelling of the clusters. After several iterations of this process, only pure labelled clusters remained which were used to train a Deep Neural Network. RESULTS: Overall, 334,548 individual signal peaks form the integrated data were extracted and more than 99.99% of the data was labelled in six iterations of this novel application of weak labelling with the help of a domain expert. A Deep Neural Network trained based on this dataset achieved consistent accuracies above 95%. DISCUSSION: Data extraction and the novel iterative approach of labelling unsupervised clusters enabled creation of a large, labelled dataset combining unsupervised learning and expert ratings of signal-peaks on cluster basis in a time effective manner. Further research is needed to validate the methodology and employ it on other types of physiologic data for which it may enable efficient generation of large labelled datasets.

Renal denervation as a management strategy for hypertension: current evidence and recommendations.

INTRODUCTION: The concept of targeting the renal sympathetic nerves therapeutically to lower blood pressure (BP) is based on their crucial role in regulating both renal and cardiovascular control. These effects are mainly mediated via three major mechanisms including alteration of renal blood flow, renin-release, and Na+ retention. Initial surgical approaches applying crude and unselected sympathectomy, while rendering significant BP lowering and cardiovascular event reducing properties, where plagued by side effects. More modern selective catheter-based denervation approaches selectively targeting the renal nerves have been shown to be safe and effective in reducing BP in various forms of hypertension and multiple comorbidities. AREAS COVERED: This article covers the background relevant for the concept of renal denervation (RDN), the evidence obtained from relevant randomized controlled trials to substantiate the safety and efficacy of RDN, and recently published clinical recommendations. EXPERT OPINION: Catheter-based RDN is safe and has now been shown in sham-controlled randomized clinical trials to result in clinically meaningful BP lowering in both drug naïve hypertensive patients and those on concomitant antihypertensive therapy. Real world data from a large global registry further supports the clinical utility of RDN. It now seems time to embed renal denervation into routine clinical care.

Catheter ablation vs. antiarrhythmic drugs as 'first-line' initial therapy for atrial fibrillation: a pooled analysis of randomized data.

AIMS: Catheter ablation (CA) is recommended for patients with atrial fibrillation (AF) after failure of antiarrhythmic drugs (AADs). The role of CA as 'initial therapy' for AF is to be determined. METHODS AND RESULTS: Following PRISMA guideline an up-to-date pooled analysis of randomized data comparing ablation vs. AADs as first-line therapy for symptomatic AF was performed. The primary outcome was recurrence of atrial tachyarrhythmia. The secondary outcomes were improvement in quality-of-life (QoL) and major adverse events. A total of 997 patients from five randomized trials were enrolled (mean age 57.4 years, 68.6% male patients, 98% paroxysmal AF, mean follow-up 1.4 years). The baseline characteristics were similar between the ablation and AADs group. Overall pooled analysis showed that, as compared with AADs, CA as first-line therapy was associated with significantly higher freedom from arrhythmia recurrence (69% vs. 48%, odds ratio: 0.36, 95% confidence interval: 0.27-0.48, P < 0.001). This significance was maintained in subgroup analyses of 1- and 2-year follow-up (P < 0.001). Catheter ablation was associated with significantly greater improvement in QoL regarding AFEQT score and 36-Item Short-Form Health Survey score. The incidence of serious adverse events between ablation and AADs group (5.6% vs. 4.9%, P = 0.62) was similar. CONCLUSIONS: Catheter ablation as 'initial therapy' was superior to AADs in maintenance of sinus rhythm and improving QoL for patients with symptomatic paroxysmal AF, without increasing risk of serious adverse events.

Comparison of Left Atrial Appendage Occlusion versus Non-Vitamin-K Antagonist Oral Anticoagulation in High-Risk Atrial Fibrillation: An Update.

Transcatheter left atrial appendage occlusion (LAAO) is non-inferior to vitamin K antagonists (VKAs) in preventing thromboembolic events in atrial fibrillation (AF). Non-vitamin K antagonists (NOACs) have an improved safety profile over VKAs; however, evidence regarding their effect on cardiovascular and neurological outcomes relative to LAAO is limited. Up-to-date randomized trials or propensity-score-matched data comparing LAAO vs. NOACs in high-risk patients with AF were pooled in our study. A total of 2849 AF patients (LAAO: 1368, NOACs: 1481, mean age: 75 ± 7.5 yrs, 63.5% male) were enrolled. The mean CHA2DS2-VASc score was 4.3 ± 1.7, and the mean HAS-BLED score was 3.4 ± 1.2. The baseline characteristics were comparable between the two groups. In the LAAO group, the success rate of device implantation was 98.8%. During a mean follow-up of 2 years, as compared with NOACs, LAAO was associated with a significant reduction of ISTH major bleeding (p = 0.0002). There were no significant differences in terms of ischemic stroke (p = 0.61), ischemic stroke/thromboembolism (p = 0.63), ISTH major and clinically relevant minor bleeding (p = 0.73), cardiovascular death (p = 0.63), and all-cause mortality (p = 0.71). There was a trend toward reduction of combined major cardiovascular and neurological endpoints in the LAAO group (OR: 0.84, 95% CI: 0.64-1.11, p = 0.12). In conclusion, for high-risk AF patients, LAAO is associated with a significant reduction of ISTH major bleeding without increased ischemic events, as compared to "contemporary NOACs". The present data show the superior role of LAAO over NOACs among high-risk AF patients in terms of reduction of major bleeding; however, more randomized controlled trials are warranted.

Combined renal and common hepatic artery denervation as a novel approach to reduce cardiometabolic risk: technical approach, feasibility and safety in a pre-clinical model.

BACKGROUND: Cardiovascular and metabolic regulation is governed by neurohumoral signalling in relevant organs such as kidney, liver, pancreas, duodenum, adipose tissue, and skeletal muscle. Combined targeting of relevant neural outflows may provide a unique therapeutic opportunity for cardiometabolic disease. OBJECTIVES: We aimed to investigate the feasibility, safety, and performance of a novel device-based approach for multi-organ denervation in a swine model over 30 and 90 days of follow-up. METHODS: Five Yorkshire cross pigs underwent combined percutaneous denervation in the renal arteries and the common hepatic artery (CHA) with the iRF Denervation System. Control animals (n = 3) were also studied. Specific energy doses were administered in the renal arteries and CHA. Blood was collected at 30 and 90 days. All animals had a pre-terminal procedure angiography. Tissue samples were collected for norepinephrine (NEPI) bioanalysis. Histopathological evaluation of collateral structures and tissues near the treatment sites was performed to assess treatment safety. RESULTS: All animals entered and exited the study in good health. No stenosis or vessel abnormalities were present. No significant changes in serum chemistry occurred. NEPI concentrations were significantly reduced in the liver (- 88%, p = 0.005), kidneys (- 78%, p < 0.001), pancreas (- 78%, p = 0.018) and duodenum (- 95%, p = 0.028) following multi-organ denervation treatment compared to control animals. Histologic findings were consistent with favourable tissue responses at 90 days follow-up. CONCLUSIONS: Significant and sustained denervation of the treated organs was achieved at 90 days without major safety events. Our findings demonstrate the feasibility of multi-organ denervation using a novel iRF Denervation System in a single procedure.

Increased pulse wave velocity in patients with an orthostatic blood pressure rise independent of other cardiovascular risk factors.

BACKGROUND: Positional changes in blood pressure (BP) have been shown to have effects on long-term outcomes. Although a BP drop with upright posture is frequently observed, an orthostatic rise in BP can also occur. Here, we aimed to investigate whether the phenotype of orthostatic hypertension is associated with more pronounced vascular hypertension-mediated organ damage (HMOD) and whether this is associated with other cardiovascular risk factors. METHODS: In a cohort of 200 patients referred to our tertiary hypertension clinic, we prospectively assessed unattended seated automated office BP and the response to 1 min of upright posture. The difference in BP after standing up was calculated and pulse wave velocity (PWV) was assessed as a marker of vascular HMOD. Routine clinical cardiovascular risk markers were also assessed. Regression models were used to assess the association between orthostatic BP changes and pulse wave velocity. RESULTS: Baseline characteristics and clinic cardiovascular risk factors were similar between orthostatic BP response groups. A U-shaped association was evident between PWV and orthostatic BP changes with elevated PWV in patients with either a fall or a rise in BP in response to upright posture. The regression models remained significant after adjusting for other cardiovascular risk factors, including 24 h ambulatory BP. CONCLUSION: Both an orthostatic BP drop and rise were associated with elevated PWV. Although standing BP is commonly measured in elderly hypertensive patients to exclude significant orthostatic hypotension, this simple measurement may provide an additional independent risk factor for vascular HMOD at any age.

Nocturnal hypertension: a common phenotype in a tertiary clinical setting associated with increased arterial stiffness and central blood pressure.

OBJECTIVE: Although the detrimental effect of increased mean blood pressure (BP) is well established, the role of the dynamic and circadian features of BP is less well defined but may be similarly important. In this prospective analysis of hypertensive patients from a tertiary hospital hypertension clinic, we investigated whether the presence of night-time systolic hypertension is associated with more pronounced end-organ damage as assessed by measures of pulse wave analysis (PWA) and pulse wave velocity (PWV). METHODS: A cohort of 222 consecutive hypertensive patients underwent ambulatory blood pressure measurements, PWA, PWV testing and collection of routine clinical data. Group differences and group-effects of daytime and night-time hypertension on target organ damage and cardiovascular risk parameters were analysed. RESULTS: Nocturnal hypertension was evident in more than half of the study population. PWV, central systolic, mean arterial and pulse pressure were higher in patients with nocturnal hypertension. Stratification into four groups according to daytime and night-time hypertension status revealed group differences in all outcome parameters. Posthoc testing for individual group differences demonstrated significant differences between fully controlled individuals and the group with high daytime and night-time BP. In a regression analysis for independent effects of categorical night-time and daytime hypertension, nocturnal hypertension was a significant predictor for all PWA and PWV outcomes. CONCLUSION: Nocturnal hypertension was a highly prevalent phenotype in this population and associated with increased central BP and more pronounced target organ damage as indicated by elevated PWV. Regression analysis confirmed the role of night-time hypertension as an independent explanatory variable for elevated PWV.

Supine blood pressure-A clinically relevant determinant of vascular target organ damage in hypertensive patients.

Night-time blood pressure (BP) is an important predictor of cardiovascular outcomes. Its assessment, however, remains challenging due to limited accessibility to ambulatory BP devices in many settings, costs, and other factors. We hypothesized that BP measured in a supine position during daytime may perform similarly to night-time BP when modeling their association with vascular hypertension-mediated organ damage (HMOD). Data from 165 hypertensive patients were used who as part of their routine clinic workup had a series of standardized BP measurements including seated attended office, seated and supine unattended office, and ambulatory BP monitoring. HMOD was determined by assessment of kidney function and pulse wave velocity. Correlation analysis was carried out, and univariate and multivariate models were fitted to assess the extent of shared variance between the BP modalities and their individual and shared contribution to HMOD variables. Of all standard non-24-hour systolic BP assessments, supine systolic BP shared the highest degree of variance with systolic night-time BP. In univariate analysis, both systolic supine and night-time BP were strong determinants of HMOD variables. In multivariate models, supine BP outperformed night-time BP as the most significant determinant of HMOD. These findings indicate that supine BP may not only be a clinically useful surrogate for night-time BP when ambulatory BP monitoring is not available, but also highlights the possibility that unattended supine BP may be more closely related to HMOD than other BP measurement modalities, a proposition that requires further investigations in prospective studies.

Microvascular changes at different stages of chronic kidney disease.

Patients with progressing chronic kidney disease (CKD) are more likely to experience cardio- and cerebrovascular events than progressing to end-stage renal disease. The authors explored whether retinal microvascular calibers differed with the degree of renal impairment and between the standard and extended optic disk and may serve as a simple additional tool for risk stratification in this highly vulnerable patient cohort. The authors analyzed central retinal arteriolar and venular equivalent calibers (CRAE, CRVE) at different retinal zones (zone B&C) using digital retinal imaging in hypertensive patients with stage 2 (n = 66) or stage 3 CKD (n = 30). Results were adjusted for age, sex, HbA1c, and 24-hour diastolic blood pressure. Mean eGFR was 77.7 ± 8.9 and 48.8 ± 7.9 ml/min/1.73 m2 for stage 2 and 3 CKD, respectively. CRAE and CRVE in zones B and C were significantly lower in patients with stage 3 CKD compared to patients with stage 2 CKD (CRAE-B:141.1 ± 21.4 vs. 130.5 ± 18.9 µm, p = .030; CRAE-C:137.4 ± 19.4 vs 129.2 ± 18.2 µm, p = .049; CRVE-B:220.8 ± 33.0 vs. 206.0 ± 28.4 µm, p = .004; and CRVE-C:215.9 ± 33.0 vs. 201.2 ± 25.1µm, p = .003). In patients with stage 2 CKD, CRAE-B was higher than CRAE-C (141.1 ± 21.4 vs. 137.4 ± 19.4µm, p < .001). In contrast, such a difference was not found in patients with stage 3 CKD. CRAE of both retinal zones correlated with eGFR for the entire cohort. In patients with stage 3 CKD, retinal narrowing is more pronounced compared to patients with stage 2 CKD. Whether the novel observation of difference in arteriolar caliber between zones B and C in stage 2 CKD could serve as an early marker of CKD progression warrants further investigation.

Interventional Approaches for Loin Pain Hematuria Syndrome and Kidney-Related Pain Syndromes.

PURPOSE OF REVIEW: Loin pain hematuria syndrome (LPHS) frequently presents with severe chronic pain that poses a clinical challenge. Current treatment approaches are mostly empirical and include a wide range of therapeutic strategies such as physical therapy, local and systemic analgesia, interventional and surgical approaches usually flanked by psycho-behavioral therapy, and other strategies. LPHS often impacts negatively on quality of life particularly in patients who are refractory to treatment. RECENT FINDINGS: With recent advances in catheter-based treatment approaches and better understanding of the pathophysiology of LPHS, intraluminal renal denervation (RDN) has been proposed as a valuable treatment option for kidney-related pain syndromes. The present review provides a brief overview of the clinical challenges associated with LPHS, highlights recent insights into its underlying mechanisms, and summarizes currently available data on the use of RDN in the context of LPHS and kidney-related pain syndromes. Renal denervation via various approaches including surgical and catheter-based techniques has shown promise in alleviating kidney-related pain syndromes. Randomized controlled trials are now required to better define its role in the management of these conditions.