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More than 1.5 billion people worldwide have arterial hypertension. Hypertension increases the risks of death and cardiovascular disease, such as atrial fibrillation and heart failure. The autonomic nervous system plays an essential role in hypertension development and disease progression. While lifestyle factors, such as obesity and obstructive sleep apnea, predispose to hypertension by increasing sympathetic activity, hypertension itself maintains the autonomic nervous imbalance, providing the substrate for atrial fibrillation and heart failure. Therefore, autonomic nervous system modulation either by direct targeting or indirect treatment of comorbidities has the potential to treat both hypertension and related atrial and ventricular end-organ damage. We discuss interventions for the modulation of the autonomic nervous system for hypertension and related cardiac end-organ damage, including pharmacological adrenergic beta-receptor blockade, renal denervation, carotid baroreceptor stimulation, low-level vagal stimulation, and ablation of ganglionated plexuses. In summary, the literature suggests that targeting the autonomic nervous system potentially represents a therapeutic approach to prevent atrial and ventricular end-organ damage in patients with hypertension. However, clinical trials specifically designed to test the effect of autonomic modulation on hypertension-mediated cardiac end-organ damage are scarce. [ABSTRACT FROM AUTHOR]

Hypertension is prevalent in >70% of atrial fibrillation patients. In turn, hypertensive patients have up to 73% greater likelihood of atrial fibrillation. Current guidelines recommend that a systematic atrial fibrillation screening may be justified in all patients aged ≥65 years with at least 1 cardiovascular disease, including hypertension. Although most blood pressure monitors include algorithms to detect atrial fibrillation with a high sensitivity of 96 [92–98]% and specificity of 94 [91–96]%, an electrocardiography confirmation is necessary to establish a diagnosis of atrial fibrillation. Early detection and diagnosis of atrial fibrillation is important to allow initiation of atrial fibrillation management. In the Early Treatment of Atrial Fibrillation for Stroke Prevention Trial (EAST-AFNET 4), hypertension was present in 88% of participants, and early rhythm control therapy lowered the risk of adverse cardiovascular outcomes in patients with early atrial fibrillation aged >75 or with CHA2DS2-VASc score ≥2 (Congestive heart failure, Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65–74, Sex category [female]) and cardiovascular condition. Strategies for early atrial fibrillation detection should always be linked to a comprehensive atrial fibrillation work-up infrastructure organized within an integrated ABC pathway (Anticoagulation/Avoid stroke; Better symptom control; Cardiovascular and Comorbidity optimization). For secondary prophylaxis, blood pressure control should be embedded in a combined risk factor management program. In hypertensive patients where no atrial fibrillation is detected, intensive blood pressure lowering therapy for primary prophylaxis should be initiated to reduce the risk of developing atrial fibrillation and other cardiovascular complications in the future. The aim of the article is to review the current literature on atrial fibrillation detection and management in hypertensive patients. [ABSTRACT FROM AUTHOR]

Intermitting... Although the here presented data are derived from a small number of subjects we could verify earlier findings of sunitinib treatment on blood pressure and on circulating endothelin-1 and VEGF levels.[5],[6] More importantly, it was enough powered to detect clear changes in skin sodium content and in plasma VEGF-C concentrations; sunitinib treatment decreased VEGF-C levels and led to an increase of skin sodium content. In contrast to VEGF-A, high baseline VEGF-C concentrations dropped after sunitinib treatment and stayed low independently from further treatment phase of sunitinib (Figure [F]). Our findings also suggest that whereas a side-effect such as blood pressure elevation is a reversible phenomenon of a sunitinib treatment, it could have a long-lasting effect on plasma VEGF-C concentrations and thereby on skin sodium homeostasis. [Extracted from the article]

Background: The posterior left atrium is an arrhythmogenic substrate that contributes to the initiation and maintenance of atrial fibrillation (AF); however, the feasibility, safety, and efficacy of posterior wall isolation (PWI) as an AF ablation strategy has not been widely reported.Methods: We undertook a systematic review and meta-analysis of studies performing PWI to assess (1) acute procedural success including the ability to achieve PWI and the number of procedure-related complications, (2) Long-term, clinical success including rates of arrhythmia recurrence and posterior wall reconnection, and (3) The efficacy of PWI compared with pulmonary vein isolation on preventing arrhythmia recurrence. MEDLINE, EMBASE, and Web of Science databases were searched in May 2018 to retrieve relevant studies. Results were pooled using a random effects model.Results: Seventeen studies (13 box isolation, 3 single ring isolation, and 1 debulking ablation) comprising 1643 patients (31.3% paroxysmal AF, left atrial diameter 41±3.1 mm) were included in the final analysis. In studies focusing specifically on PWI, the acute procedural success rate for achieving PWI was 94.1% (95% CI, 87.2%-99.3%). Single-procedure 12-month freedom from atrial arrhythmia was 65.3% (95% CI, 57.7%-73.9%) overall and 61.9% (54.2%-70.8%) for persistent AF. Randomized control trials comparing PWI to pulmonary vein isolation (3 studies, 444 patients) yielded conflicting results and could not confirm an incremental benefit to PWI. Fifteen major complications (0.1%), including 2 atrio-esophageal fistulas, were reported.Conclusions: PWI as an end point of AF ablation can be achieved in a large proportion of cases with good rates of 12-month freedom from atrial arrhythmia. Although the procedure-related complication rate is low, it did not eliminate the risk of atrio-esophageal fistula. Registration: URL: http://www.crd.york.ac.uk/prospero. PROSPERO registration number: CRD42018107212. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses an article in the issue on the topic of a substrate for obstructive sleep apnea (OSA)-related hypertension created by high-fat diet (HFD)-induced dysbiosis and reduced short-chain fatty acids (SCFAs) concentrations.

The article discusses a study which investigated the antihypertensive and laxative effects of pharmacological inhibition of sodium-proton-exchanger subtype 3 (NHE3)-mediated sodium absorption in the gut. The researchers studied the expression of NHE3 in the kidney and intestinal segments. It was found that intestinal NHE3 blockade had a potential as a new treatment strategy for elderly patients suffering from high blood pressure and constipation.

Hypertension is linked to disturbed total-body sodium (Na(+)) regulation; however, measuring Na(+) disposition in the body is difficult. We implemented (23)Na magnetic resonance spectroscopy ((23)Na-MR) and imaging technique ((23)Na-MRI) at 9.4T for animals and 3T for humans to quantify Na(+) content in skeletal muscle and skin. We compared (23)Na-MRI data with actual tissue Na(+) content measured by chemical analysis in animal and human tissue. We then quantified tissue Na(+) content in normal humans and in patients with primary aldosteronism. We found a 29% increase in muscle Na(+) content in patients with aldosteronism compared with normal women and men. This tissue Na(+) was mobilized after successful treatment without accompanying weight loss. We suggest that, after further refinements, this tool could facilitate understanding the relationships between Na(+) accumulation and hypertension. Furthermore, with additional technical advances, a future clinical use may be possible. [ABSTRACT FROM AUTHOR]

Despite the global COVID-19 pandemic, during the past 2 years, there have been numerous advances in our understanding of arrhythmia mechanisms and diagnosis and in new therapies. We increased our understanding of risk factors and mechanisms of atrial arrhythmias, the prediction of atrial arrhythmias, response to treatment, and outcomes using machine learning and artificial intelligence. There have been new technologies and techniques for atrial fibrillation ablation, including pulsed field ablation. There have been new randomized trials in atrial fibrillation ablation, giving insight about rhythm control, and long-term outcomes. There have been advances in our understanding of treatment of inherited disorders such as catecholaminergic polymorphic ventricular tachycardia. We have gained new insights into the recurrence of ventricular arrhythmias in the setting of various conditions such as myocarditis and inherited cardiomyopathic disorders. Novel computational approaches may help predict occurrence of ventricular arrhythmias and localize arrhythmias to guide ablation. There are further advances in our understanding of noninvasive radiotherapy. We have increased our understanding of the role of His bundle pacing and left bundle branch area pacing to maintain synchronous ventricular activation. There have also been significant advances in the defibrillators, cardiac resynchronization therapy, remote monitoring, and infection prevention. There have been advances in our understanding of the pathways and mechanisms involved in atrial and ventricular arrhythmogenesis. [ABSTRACT FROM AUTHOR]

Renal denervation can reduce blood pressure in certain patients with resistant hypertension. The effect in patients with isolated systolic hypertension (ISH, ≥140/<90 mm Hg) is unknown. This study investigated the effects of renal denervation in 126 patients divided into 63 patients with ISH and 63 patients with combined hypertension (CH, ≥140/≥90 mm Hg) defined as baseline office systolic blood pressure (SBP) ≥140 mm Hg despite treatment with ≥3 antihypertensive agents. Renal denervation significantly reduced office SBP and diastolic blood pressure (DBP) at 3, 6, and 12 months by 17/18/17 and 5/4/4 mm Hg in ISH and by 28/27/30 and 13/16/18 mm Hg in CH, respectively. The reduction in SBP and DBP in ISH was lower compared with patients with CH at all observed time points (P<0.05 for SBP/DBP intergroup comparison). The nonresponder rate (change in office SBP <10 mm Hg) after 6 months was 37% in ISH and 21% in CH (P<0.001). Mean 24-hour ambulatory SBP and DBP after 3, 6, and 12 months were significantly reduced by 10/13/15 and 6/6/9 mm Hg in CH, respectively. In patients with ISH the reduction in systolic ambulatory blood pressure was 4/8/7 mm Hg (P=0.032/P<0.001/P=0.009) and 3/4/2 mm Hg (P=0.08/P<0.001/P=0.130) in diastolic ambulatory blood pressure after 3, 6, and 12 months, respectively. The ambulatory blood pressure reduction was significantly lower after 3 and 12 months in SBP and after 12 months in ambulatory DBP, respectively. In conclusion, renal denervation reduces office and ambulatory blood pressure in patients with ISH. However, this reduction is less pronounced compared with patients with CH. [ABSTRACT FROM AUTHOR]

In selected patients with hypertension, renal artery (RA) stenting is used to treat significant atherosclerotic stenoses. However, blood pressure often remains uncontrolled after the procedure. Although catheter-based renal denervation (RDN) can reduce blood pressure in certain patients with resistant hypertension, there are no data on the feasibility and safety of RDN in stented RA.We report marked blood pressure reduction after RDN in a patient with resistant hypertension who underwent previous stenting. Subsequently, radiofrequency ablation was investigated within the stented segment of porcine RA, distal to the stented segment, and in nonstented RA and compared with stent only and untreated controls. There were neither observations of thrombus nor gross or histological changes in the kidneys. After radiofrequency ablation of the nonstented RA, sympathetic nerves innervating the kidney were significantly reduced, as indicated by significant decreases in sympathetic terminal axons and reduction of norepinephrine in renal tissue. Similar denervation efficacy was found when RDN was performed distal to a renal stent. In contrast, when radiofrequency ablation was performed within the stented segment of the RA, significant sympathetic nerve ablation was not seen. Histological observation showed favorable healing in all arteries.Radiofrequency ablation of previously stented RA demonstrated that RDN provides equally safe experimental procedural outcomes in a porcine model whether the radiofrequency treatment is delivered within, adjacent, or without the stent struts being present in the RA. However, efficacious RDN is only achieved when radiofrequency ablation is delivered to the nonstented RA segment distal to the stent. [ABSTRACT FROM AUTHOR]

Renal denervation reduces office blood pressure in patients with resistant hypertension. This study investigated the effects of renal denervation on blood pressure, heart rate, and chronotropic index at rest, during exercise, and at recovery in 60 patients (renal denervation group=50, control group=10) with resistant hypertension using a standardized bicycle exercise test protocol performed 6 and 12 months after renal denervation. After renal denervation, exercise blood pressure at rest was reduced from 158±3/90±2 to 141±3/84±4 mmHg (P<0.001 for systolic blood pressure/P=0.007 for diastolic blood pressure) after 6 months and 139+3/83-+4 mmHg (P<0.001/P=0.022) after 12 months. Exercise blood pressure tended to be lower at all stages of exercise at 6- and 12-month follow-up in patients undergoing renal denervation, although reaching statistical significance only at mild-to-moderate exercise levels (75-100 W). At recovery alter 1 minute, blood pressure decreased from 201±4/95±2 to 177v4/88±2 (P<0.001/P=0.066) and 188±6/86±2 mm (P=0.059/P=0.01) after 6 and 12 months, respectively. Heart rate was reduced after renal denervation from 71±3 bpm at rest, 128±5 bpm at maximum workload, and 96±5 bpm at recovery after 1 minute to 66±2 (P<0.001), 115±5 (P=0.1 and 89±3 bpm (P=0.008) after 6 months and to 69±3 (P=0.092), 122±7 (P=0.01), and 93±4 bpm (P=0.032) after months. Mean exercise time increased from 6.59±0.33 to 8.4+0.32 (P<0.001) and 9.0±0.41 minutes (P=0.008), a mean workload increased from 93±2 to 100 ±2 (P<0.001) and 101±3 W (P=0.007) at 6- and 12-month follow-up, respectively. No changes were observed in the control group. In conclusion, renal denervation reduced blood pressure and heart rate during exercise, improved mean workload, and increased exercise time without impairing chronotropic competence. [ABSTRACT FROM AUTHOR]

Obstructive sleep apnea is characterized by repetitive collapses of the upper airway, negative thoracic pressure periods, and intermittent hypoxia, stimulating the autonomic nervous system. The increased sympathetic drive during obstructive sleep apnea results in postapneic blood pressure rises and neurohumoral activation potentially involved in the initiation and progression to permanent atrial fibrillation (AF). In a pig model mimicking obstructive sleep apnea, we studied the effects of repetitive obstructive respiratory events for 4 hours on the occurrence of spontaneous AF episodes, postapneic blood pressure rises, and neurohumoral activation. In addition, renal sympathetic denervation was performed to investigate the impact of the sympathetic nervous system. Repetitive obstructive respiratory events caused pronounced postapneic blood pressure rises, prolonged duration of spontaneous AF episodes triggered by spontaneous atrial beats, and increased plasma renin activity and aldosterone concentrations. This was associated with increased nicotinamide adenine dinucleotide phosphate-oxidase activity, reduced antioxidative capacity, and elevated expression of connective tissue growth factor, a redox-sensitive mediator of fibrosis. Renal sympathetic denervation inhibited postapneic blood pressure rises and decreased plasma renin activity and aldosterone concentrations. The occurrence and duration of spontaneous AF were reduced comparable with a combined pharmacological blockade of angiotensin receptor and β-adrenoceptor. Increased atrial oxidative stress, together with the activation of profibrotic pathways and intermittent hypoxia, was not attenuated after renal sympathetic denervation. Repetitive obstructive respiratory events triggered spontaneous AF, increased atrial oxidative stress, and activated profibrotic pathways in the atrium. Renal sympathetic denervation reduced spontaneous AF and postapneic blood pressure rises by combined reduction of sympathetic drive and components of the circulating renin--angiotensin system. However, the generation of atrial oxidative stress was not modulated. [ABSTRACT FROM AUTHOR]

High dietary salt intake is associated with hypertension; the prevalence of salt-sensitive hypertension increases with age. We hypothesized that tissue Na(+) might accumulate in hypertensive patients and that aging might be accompanied by Na(+) deposition in tissue. We implemented (23)Na magnetic resonance imaging to measure Na(+) content of soft tissues in vivo earlier, but had not studied essential hypertension. We report on a cohort of 56 healthy control men and women, and 57 men and women with essential hypertension. The ages ranged from 22 to 90 years. (23)Na magnetic resonance imaging measurements were made at the level of the calf. We observed age-dependent increases in Na(+) content in muscle in men, whereas muscle Na(+) content did not change with age in women. We estimated water content with conventional MRI and found no age-related increases in muscle water in men, despite remarkable Na(+) accumulation, indicating water-free Na(+) storage in muscle. With increasing age, there was Na(+) deposition in the skin in both women and men; however, skin Na(+) content remained lower in women. Similarly, this sex difference was found in skin water content, which was lower in women than in men. In contrast to muscle, increasing Na(+) content was paralleled with increasing skin water content. When controlled for age, we found that patients with refractory hypertension had increased tissue Na(+) content, compared with normotensive controls. These observations suggest that (23)Na magnetic resonance imaging could have utility in assessing the role of tissue Na(+) storage for cardiovascular morbidity and mortality in longitudinal studies. [ABSTRACT FROM AUTHOR]

The article presents a study on the relationship between dietary salt intake and hypertension. The study involves the use of quantitative sodium magnetic resonance imaging (Na-MRI) in visualizing Na+ in the skin and soft tissues. The noninvasive quantification of Na+ concentrations in the skin and skeletal muscle in humans using Na-MRI is cited as an key finding of the study. Results indicate an increase in Na+ storage in patients with refractory hypertension.

The article discusses the results of a study that examines the reduced ventricular heart rate of a patient with permanent atrial fibrillation (AF) undergoing renal denervation (RDN). The study shows that RDN reduced heart rate and increased atrioventricular node conduction time during sinus rhythm. It concludes that rate control and reduce susceptibility to AF may be achieved through modulation of the autonomic nervous system by RDN.

The article explores the renal hemodynamics and renal function of resistant hypertensive patients after their catheter-based renal sympathetic denervation (RD). In the study by the authors, they observed 100 patients, which includes 88 who underwent interventional RD while the remaining were controls. The participants' systolic, diastolic and renal resistive index in interlobar arteries were among those measured. They found that there number of patients with microalbuminuria decreased.

The article discusses a study which identified the impact of adrenergic and cholinergic activity on atrial fibrillation (AF) inducibility and blood pressure (BP) in a model for obstructive sleep apnea (OSA). Several conditions associated with OSA include sympathovagal disbalance, AF and postapneic BP increases. In other study, it was demonstrated that negative tracheal pressure (NTP) during obstructive respiratory events resulted to shortening of the atrial effective refractory period (AERP).

Recent advances in basic and clinical research have identified Rho kinase as an important target potentially implicated in a variety of cardiovascular diseases. Rho kinase is a downstream mediator of RhoA that leads to stress fiber formation, membrane ruffling, smooth muscle contraction, and cell motility. Increased Rho-kinase activity is associated with vasoconstriction and elevated blood pressure. We identified a novel inhibitor of Rho kinase (SAR407899) and characterized its effects in biochemical, cellular, tissue-based, and in vivo assays. SAR407899 is an ATP-competitive Rho-kinase inhibitor, equipotent against human and rat-derived Rho-kinase 2 with inhibition constant values of 36 nM and 41 nM, respectively. It is highly selective in panel of 117 receptor and enzyme targets. SAR407899 is approximately 8-fold more active than fasudil. In vitro, SAR407899 demonstrated concentration-dependent inhibition of Rho-kinase-mediated phosphorylation of myosin phosphatase, thrombin-induced stress fiber formation, platelet-derived growth factor-induced proliferation, and monocyte chemotactic protein-1-stimulated chemotaxis. SAR407899 potently (mean IC(50) values: 122 to 280 nM) and species-independently relaxed precontracted isolated arteries of different species and different vascular beds. In vivo, over the dose range 3 to 30 mg/kg PO, SAR407899 lowered blood pressure in a variety of rodent models of arterial hypertension. The antihypertensive effect of SAR407899 was superior to that of fasudil and Y-27632. In conclusion, SAR407899 is a novel and potent selective Rho-kinase inhibitor with promising antihypertensive activity. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. [ABSTRACT FROM AUTHOR]

Introduction: Renal denervation has been shown to be effective in patients with hypertension. Recently, we found that afferent renal neurons show a distinctive feature, exhibiting predominantly a sustained firing upon current injection due to a specific expression of TTX resistant Na-channels. So far, the activity of these specific sensory neurons in hypertension is unclear. Hence we wanted to test the hypothesis that the firing pattern of renal afferent neurons is altered in the 2K/1C model of hypertension.Methods: Hypertension was induced by unilateral clipping of the renal artery in Sprague Dawley rats 3 weeks prior to experiments. Blood pressure was confirmed by an intraarterial measurement. Retrograde labelling (DiI) allowed the identification of renal afferent neurons in the Dorsal root ganglion (DRG Th11-L2). Current clamp was used to characterize neurons as “tonic”, i.e. sustained action potential (AP) firing or “phasic”, i.e. <5 APs according to their firing upon current injections. Electrophysiological parameters and AP properties were determined in neurons of hypertensive animals and controls. Renal morphology was investigated.Results: Renal DRG neurons of hypertensive animals (n=88) showed a significant decrease in tonic firing pattern compared to controls (n=84) (44.3% [39/88] vs. 59.5% [50/84], p< 0.05). Current Clamp analysis revealed no significant change in action potential shape in hypertensive animals (overshoot, firing threshold, AP- duration). Tonic cells revealed a higher capacity in hypertensive rats (124pF vs. 87.8pF, p<0.01), all other parameters (resting potential, resistances) were equal in both groups. No differences in renal pathomorphology could be observed between clipped and non-clipped kidney in hypertensive animals. (BP: 187.5 mmHg versus controls: 106.5mmHg)Conclusion: Hence the excitability of afferent renal neurons in a model of renovascular hypertension is significantly altered, as renal afferent DRG neurons exhibit less sustained firing upon stimulation. Sustained high blood pressure is possibly rather characterized by a generally decreased afferent renal activity with impaired sympathoinhibition than by activated sympathoexcitatory fibers from the clipped kidney. [ABSTRACT FROM AUTHOR]

Hypertension is the most common cardiovascular risk factor and systolic blood pressure increases continuously with age. Increased vascular stiffness, nitric oxide, renin-angiotensin aldosterone system and salt intake have been implicated. We have developed 23Na magnetic resonance imaging (23Na MRI) and showed that aldosterone influences tissue Na+ storage. We reasoned that Na+ might accumulate in tissues with age. We investigated tissue Na+ of the lower leg in 113 subjects with 3T 23Na MRI. Tissue Na+ concentration was calibrated by solutions containing 10 to 40 mmol/l of Na+. Prior to 23Na MRI measurements, a medical history was taken, blood and urine samples were obtained and blood pressure was analyzed in seated position. The age of the 113 subjects analyzed by 23Na MRI ranged from 22 to 90 years. We studied 44 women and 69 men. Hypertension was diagnosed in 46 subjects (29 men and 17 women). Men showed an exponential increase in tissue Na+ with age (muscle R2 = 0.54, skin R2= 0.33). In contrast, tissue Na+ in women was only slightly affected by age and increased linearly (skin R2 = 0.40, muscle R2= 0.13). To compare subpopulations, we allocated the participants into three different age groups <50, 50-65 and >65 years. A gender difference in skin tissue Na+ could be found throughout all groups with higher levels in men (14.3 vs. 18.1 (<50 yrs), 19.0 vs. 24.5 (50-65 yrs), 20.1 vs. 27.4 mmol/l (>65 yrs); p < 0.05). Skin Na+ content was elevated in hypertensive women compared to age-matched controls (17.2, n = 12 vs. 21.0 mmol/l, n = 17; p<0.05). We could not identify such a difference in hypertensive versus normotensive men. In line with our previous results, older hypertensive patients receiving an aldosterone antagonist revealed muscle Na+ values below age-matched subjects (17.6, n = 6 vs. 21.3 mmol/l, n = 24; p < 0.05). We conclude that aging is associated with Na+ tissue accumulation with a pronounced gender difference. Skin Na+ overload occurs in hypertensive women but not in men. Aldosterone antagonists may reset the age-dependent muscle Na+ overload to levels of young healthy controls. [ABSTRACT FROM AUTHOR]