Search Results (58)

Hypertension is the leading global risk factor for cardiovascular diseases, and its pathogenesis is closely linked to excessive sympathetic activation, which markedly elevates the risk of stroke, heart failure and other adverse cardiovascular events. Traditional therapies mainly target peripheral mechanisms, whereas the clinical efficacy of renal denervation highlights the critical role of central regulation in sympathetic hyperactivity. This review focuses on the core sympathetic nuclei including the rostral ventrolateral medulla (RVLM) and paraventricular nucleus (PVN), with epigenetic regulation as a key innovative perspective. We systematically summarize the upstream driving effects of reactive oxygen species (ROS) and neuroinflammation, and emphasize lncRNA/miRNA-mediated post-transcriptional regulation and the modulatory actions of gasotransmitters. Under stress conditions, aberrant activation of ROS and neuroimmune pathways, epigenetic reprogramming, and hyperexcitability of central sympathetic neurons act as key events in sympathetic overactivation, which interact synergistically to promote hypertension. Integrating evidence from multiple hypertensive animal models and clinical studies, we discuss multimodal interventions including pharmacotherapy, nanozyme biotechnology and neuromodulation, analyze current translational challenges, and provide a theoretical framework for developing central-targeted antihypertensive therapies. Full article

Background/Objectives: Renal denervation (RDN) has re-emerged as an adjunctive treatment option for patients with uncontrolled or resistant hypertension, with contemporary sham-controlled trials showing a modest but reproducible reduction in out-of-office blood pressure. However, in routine practice, apparent treatment resistance often reflects pseudoresistance caused by the white-coat effect, poor measurement quality, therapeutic inertia, or nonadherence. This review aimed to summarize the contemporary evidence on renal denervation in uncontrolled or resistant hypertension and to propose a pragmatic, measurement-first framework for patient selection, integration into routine care, and a structured post-procedural response assessment. Methods: This article is a narrative, implementation-focused review. A structured search of PubMed, Embase, Cochrane CENTRAL, and Web of Science was performed from database inception through January 2026. We prioritized the randomized sham-controlled RDN trials, major meta-analyses, guidelines, consensus documents, and studies addressing ABPM, HBPM, medication adherence, and telemonitoring. Results: The contemporary sham-controlled trials support RDN as an adjunctive option with a modest blood pressure-lowering effect, which is best assessed by out-of-office measurements. The placebo-adjusted reductions in ambulatory systolic blood pressure were generally in the 4–6 mmHg range. Appropriate use requires the confirmation of sustained uncontrolled hypertension, the exclusion of pseudoresistance, the optimization of treatment, and an adherence assessment. We identified three phenotypes most likely to benefit and proposed a three-axis framework for a response assessment at 3 and 6 months. Conclusions: RDN should be viewed not as a substitute for antihypertensive therapy but as a program-based adjunct for carefully selected patients. The measurement-first care pathway presented here should be interpreted as a pragmatic clinical model intended to operationalize the available trial and guideline evidence in routine care, rather than as a prospectively validated algorithm or formal consensus recommendation. Full article

Hypertension is highly prevalent among patients with chronic kidney disease (CKD), contributing significantly to cardiovascular morbidity and progressive renal decline. This overview explores the intricate pathophysiologic mechanisms driving hypertension in renal insufficiency, including volume overload, renin–angiotensin–aldosterone system (RAAS) activation, sympathetic overactivity, and vascular dysfunction. Diagnostic challenges such as white-coat hypertension and the underuse of ambulatory monitoring are discussed, along with the importance of volume assessment and target organ evaluation. We also emphasize individualized management strategies combining lifestyle modification, pharmacotherapy—including RAAS inhibitors, diuretics, and novel agents—and the growing role of device-based interventions. In particular, renal denervation (RDN) has emerged as a potential adjunctive option for selected patients with resistant hypertension in CKD, with preliminary evidence suggesting blood pressure reduction in selected and carefully studied populations, including dialysis-dependent patients. Special considerations for transplant recipients, elderly individuals, and those on dialysis are highlighted, underscoring the need for nuanced, patient-centered care. Misconceptions surrounding RAAS blockade, dialysis hypotension, and therapeutic inertia are critically appraised. Finally, future directions point to biomarker-driven approaches, digital health integration, and large-scale trials on RDN to refine treatment paradigms. This comprehensive synthesis offers a pragmatic framework for clinicians managing hypertension in CKD, aligning mechanistic insights with emerging evidence and clinical realities. Full article

Background and Objectives: The combination of resistant hypertension (RHTN) and type 2 diabetes mellitus (T2DM) accelerates the development of chronic kidney disease (CKD), which may be largely associated with sympathetic hyperactivity. Distal renal denervation (dRDN) effectively reduces sympathetic flow to the kidneys, causing renal vasodilation and increased renal perfusion. However, this effect may be limited by nephrotoxicity due to the multiple increase in the number of contrast injections, as well as a significant blood pressure (BP) reduction, which naturally worsens renal perfusion. This study aimed to test the hypothesis that dRDN prevents the progressive decline in kidney function in patients with RHTN and T2DM. Materials and Methods: The prospective interventional study (REFRAIN, NCT04948918) included men and women > 20 y.o. with true RHTN. Eligible patients underwent dRDN. The primary endpoint was a change in eGFR from baseline to 12 months. Secondary endpoints were changes in 24 h BP, serum lipocalin-2, cystatin C, 24 h urinary albumin excretion, renal blood flow, and kidney volumes (by MRI). Multiple regression analysis was used to find independent predictors of individual estimated glomerular filtration rate (eGFR) change. Results: A total of 29 patients with RHTN and T2DM were included in the study (61.6 ± 7.2 y.o., 10 males, mean 24 h ambulatory BP: 158.1 ± 21.4/81.8 ± 12.4 mmHg (systolic/diastolic, respectively)), HbA1c: 7.8 ± 1.4%, and eGFR 56.7 ± 19.9 mL/min/1.73 m², 23 (79%) patients with CKD, and 2 patients with albuminuria only. There were no perioperative complications. Twenty-seven (93%) participants completed 12 month follow-up. eGFR did not change from baseline: +1.3 mL/min/1.73 m² [95% CI: −9.6, 12.1], despite the expected decrease due to a significant decrease in 24 h systolic BP (−18.2 mmHg [95% CI: −28.6, −7.8]). No changes in other secondary endpoints were observed. Independent predictors of individual eGFR change were baseline 24 h pulse pressure (p = 0.030) and HbA1c (p = 0.010). Conclusions: Distal RDN demonstrates a substantial nephroprotective effect in patients with RHTN and T2DM, which may be partly mediated by a reduction in arterial stiffness and is negatively dependent on baseline hyperglycemia. Full article

Cardiorenal syndrome (CRS) is a term that describes the pathological interplay between the heart and kidney wherein either organ may be the originating stimulus that leads to acute and eventually chronic disease in the other. The mechanisms by which either initial disease progression influences the target organ are multifactorial and primarily include inflammation, alternated hemodynamics and blood volume handling, and neurohormonal alterations. The order of initiation of CRS, depending on which target organ the stimulus arises from, likely impacts the overall feed-forward mechanisms of this syndrome’s pathology; however, the end results are similar: accentuated chronic inflammation and heightened autonomic output. The latter of these symptoms of CRS is especially concerning as heightened sympathetic activity enhances the risk of various other cardiovascular events such as stroke and heart attack and ultimately limits non-pharmacological options for improving quality of life such as mild to moderate exercise. The main goal of this review is to provide an overview and outline the autonomic impacts of CRS and discuss renal denervation as a mechanism of potentially limiting or impairing the autonomic positive feedback loop initiated by disease progression and its likely subsequent amplification during exercise. Full article

Arterial hypertension is highly prevalent among individuals with chronic kidney disease (CKD), exhibiting a bidirectional association and playing a critical role in the progression of renal dysfunction. CKD affects approximately 10–12% of the global population and is often a common comorbidity in patients with true resistant hypertension. The sympathetic nervous system (SNS) plays a key role in the pathophysiological cascade of CKD-mediated hypertension. Current pharmacological therapies do not directly target SNS overactivity, highlighting the need for alternative approaches. Renal denervation (RDN), an interventional procedure that modulates both afferent and efferent renal nerve signaling, has emerged as a promising strategy for resistant hypertension with multiple pleiotropic benefits. Both preclinical and clinical trial data indicate that RDN is safe, with no significant deterioration of renal function reported in both early-stage CKD and end-stage renal disease (ESRD), as well as effective in reducing both office and ambulatory blood pressure in most studies. This review examines the pathophysiological basis for SNS overactivity in CKD, summarizes preclinical and clinical data on the safety and efficacy of RDN in this population, and discusses ongoing and future trials that may further clarify the role of RDN in CKD management and its long-term impact on renal and cardiovascular outcomes. Full article

This review explores current and emerging neuromodulation techniques targeting the cardiac autonomic nervous system for the treatment and prevention of atrial and ventricular arrhythmias. Arrhythmias remain a significant cause of morbidity and mortality, with the autonomic nervous system playing a crucial role in arrhythmogenesis. Interventions span surgical, pharmacological, and bioelectronic methods. We discuss the range of neuromodulation methods targeting the stellate ganglion, the spinal region, the parasympathetic system, and other promising methods. These include stellate ganglion block, stellate ganglion ablation, cardiac sympathetic denervation, subcutaneous electrical stimulation, thoracic epidural anesthesia, spinal cord stimulation, dorsal root ganglion stimulation, vagus nerve stimulation, baroreflex activation therapy, carotid body ablation, renal denervation, ganglionated plexi ablation, acupuncture, and transcutaneous magnetic stimulation. Both preclinical and clinical studies are presented as evidence for arrhythmia management. Full article

Heart failure with preserved ejection fraction (HFpEF) is a complex and heterogeneous clinical syndrome characterized by signs and symptoms of heart failure despite normal or near-normal ejection fraction. It is a debilitating chronic disease that affects millions of people worldwide, and due to the paucity of evidence-based pharmacological treatments for HFpEF, nonpharmacological approaches as potential therapeutic alternatives are of growing interest. As a result, renal denervation (RDN), initially developed as a therapeutic tool for resistant hypertension, has become an area of active clinical interest. RDN is a catheter-based procedure that targets the renal sympathetic pathways, aiming to reduce neurohormonal activation and mitigate maladaptive cardiac remodeling. Preclinical studies in animal models have demonstrated that RDN can improve cardiac and vascular fibrosis, reduce renal inflammation, control hypertension, and alleviate endothelial dysfunction. Recent clinical studies have further highlighted the potential benefits of RDN in patients with HFpEF and uncontrolled hypertension. In this review, we aim to outline the pathophysiology of HFpEF and demonstrate the complex clinical interplay involved in how RDN impacts the heart. Moreover, we discuss the present status of clinical studies on RDN and explore its therapeutic potential as a viable treatment for HFpEF. Full article

In late 2023, the U.S. Food and Drug Administration (FDA) approved two renal denervation (RDN) systems for the treatment of hypertension. Several professional societies, including the Society of Cardiovascular Angiography and Intervention (SCAI), the American Heart Association (AHA), and numerous European associations, have recognized the potential role of RDN in managing hypertension. Despite widespread enthusiasm from clinicians, patients, and the industry, the American Medical Association’s Current Procedural Terminology (CPT) panel rejected the introduction of new codes for renal denervation at its September 2024 meeting. This article analyzes the latest evidence from clinical trials and registries, reviews current challenges in clinical practice, and explores the role of contemporary hypertension treatment from the perspective of interventional cardiologists. Full article

The sympathetic division of the autonomic nervous system plays a crucial role in maintaining homeostasis, but its overactivity is implicated in various pathological conditions, including hypertension, hyperglycaemia, heart failure, and rheumatoid arthritis. Traditional pharmacotherapies often face limitations such as side effects and poor patient adherence, thus prompting the exploration of device-based multi-organ denervation as a therapeutic strategy. Crucially, this procedure can potentially offer therapeutic benefits throughout the 24 h circadian cycle, described as an “always-on” effect independent of medication compliance and pharmacokinetics. In this comprehensive review, we evaluate the evidence behind targeted multi-organ sympathetic denervation by considering the anatomy and function of the autonomic nervous system, examining the evidence linking sympathetic nervous system overactivity to various cardiometabolic and inflammatory conditions and exploring denervation studies within the literature. So far, renal denervation, developed in 2010, has shown promise in reducing blood pressure and may have broader applications for conditions including arrhythmias, glucose metabolism disorders, heart failure, chronic kidney disease and obstructive sleep apnoea. We review the existing literature surrounding the denervation of other organ systems including the hepatic and splenic arteries, as well as the pulmonary artery and carotid body, which may provide additional physiological benefits and enhance therapeutic effects if carried out simultaneously. Furthermore, we highlight the challenges and future directions for implementing multi-organ sympathetic ablation, emphasising the need for further clinical trials to establish optimal procedural technique, efficacy and safety. Full article

Background: Heart failure (HF) is a progressive condition associated with reduced life expectancy and quality of life. Atrial fibrillation (AF), the most common arrhythmia in HF patients, significantly worsens symptoms and outcomes. The coexistence of HF and AF is linked to higher morbidity and mortality rates, with a bidirectional relationship exacerbating both conditions. The recent evidence has suggested that combining pulmonary vein isolation (PVI) with renal denervation (RDN) may offer a promising strategy for reducing AF burden and enhancing patient outcomes. Methods: This prospective interventional clinical trial aimed to assess the safety and effectiveness of a combined RDN and PVI approach compared to PVI alone. Eighteen patients, aged 18 to 80 years, with paroxysmal or persistent AF and HF (left ventricular ejection fraction [LVEF] < 50%) were enrolled. RDN was performed under general anesthesia using the four-electrode Symplicity Spyral catheter and Symplicity G3 radiofrequency generator (Medtronic). Patients were randomized to the RDN+PVI group (n = 7) or the PVI-only group (n = 11). The groups were similar in age (59 ± 8.4 years vs. 62.5 ± 11.08 years, p = NS) and baseline characteristics, including hypertension, obesity, and impaired left ventricular function (LVEF 35.86% vs. 38.54%, RDN+PVI vs. PVI only; p = NS). Results: Over a mean follow-up of 24 months, one patient died, ten were hospitalized, six underwent repeat PVI, and eight achieved AF freedom. Patients in the RDN+PVI group were significantly more likely to remain AF-free (n = 6 vs. 2; p = 0.0063). The need for repeat ablation was higher in the PVI-only group (54.5% vs. 0%), though this did not reach statistical significance. Hospitalization rates and changes in ejection fraction were similar between groups. Importantly, no procedural complications were observed. Conclusions: Combining RDN with PVI is a safe hybrid approach for AF management in HF patients, showing promising efficacy in reducing AF recurrence. Larger randomized studies are needed to confirm these findings and further explore this novel therapeutic strategy. Full article

Renal denervation to treat arterial hypertension is growing in adoption but still shows inconsistent results. Device improvement is difficult, as there is currently no way to study the immediate success of renal denervation devices in living tissue. In an effort to visualize live renal nerves surrounding their arteries using multiphoton microscopy, kidney pairs were explanted from Yorkshire pigs. They were maintained viable with a pulsatile perfusion apparatus using Visible Kidney™ methodologies, in which blood is replaced by a modified, oxygenated, and warmed (37 °C) Krebs–Henseleit buffer. The block resection allows catheter placement for nerve ablation treatment. Subsequently, the kidney block was disconnected from the perfusion system and underwent multiphoton microscopy (Nikon A1R 1024 MP). A total of three renal blocks were imaged using this model. Using 780 nm excitation for autofluorescence, we were able to selectively image peri-arterial nerves (2.5–23 μm diameter) alongside arteriolar elastin fibers (1.96 ± 0.87 μm; range: 0.3–4.27) at 25× magnification at a pixel size of 1.02 µm). Autofluoresecence was not strong enough to identify nerves at 4× magnification. There was a high but variable signal-to-noise ratio of 52.3 (median, IQR 159). This model may be useful for improving future physician training and innovations in renal denervation technologies. Full article

Hypertensive heart disease (HHD) continues to be a leading cause of cardiovascular morbidity and mortality worldwide, necessitating the evolution of evidence-based management strategies. This literature review examines the most recent updates from the 2023 and 2024 hypertension guidelines issued by the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC). These guidelines are compared with previous key recommendations, such as the 2017 American College of Cardiology/American Heart Association guidelines and the 2018 ESC/ESH guidelines. The updated recommendations reflect a paradigm shift in the approach to hypertension diagnosis and management, including a stricter systolic blood pressure (BP) target of 120–129 mmHg, which underscores the importance of early and precise BP control. The difference between the classification of “elevated BP” and hypertension in the ESC versus ESH guidelines, particularly, regarding their implications for early detection and prevention of HHD, are critically examined, highlighting areas of clinical and academic debate. The introduction of a new “elevated BP” category (120–139/70–89 mmHg) highlights a proactive strategy aimed at identifying at-risk individuals earlier in the disease course to prevent progression to HHD. Additionally, the divergent roles of hypertension-mediated organ damage (HMOD), including HHD, in risk stratification as recommended by the ESC and ESH are discussed, emphasising their significance in tailoring management approaches. For patients with resistant hypertension, the 2023 and 2024 updates also endorse innovative therapies, such as renal denervation, an interventional procedure that has demonstrated significant promise in managing treatment-resistant cases. This review synthesises these updates, focusing on their implications for clinical practice in diagnosing and managing HHD. By emphasising aggressive intervention and the integration of novel treatment modalities, the review aims to bridge existing gaps in earlier approaches to hypertension management. The critical evaluation of guideline discrepancies and evolving evidence seeks to provide clinicians with a nuanced understanding to optimise outcomes for patients with HHD, particularly considering emerging therapeutic possibilities and more stringent BP control targets. Full article

Hypertension remains a critical global health challenge, significantly contributing to cardiovascular morbidity and mortality despite advancements in treatment. The 2024 ESC hypertension guidelines address persistent gaps in hypertension management by emphasizing comprehensive strategies encompassing early detection, socioeconomic barriers, lifestyle interventions, and personalized care. Enhanced screening protocols, including home and ambulatory blood pressure monitoring, aim for accurate diagnosis and risk stratification. Lifestyle recommendations now prioritize reducing sodium intake, increasing potassium consumption, and integrating tailored exercise regimens. Pharmacological updates advocate for single-pill combinations and stringent BP targets (<130/80 mmHg), emphasizing the benefits of sodium-glucose cotransporter-2 inhibitors for specific comorbidities. Minimally invasive therapies like renal denervation are explored for resistant hypertension, while digital tools such as telehealth and mobile applications enhance patient engagement and adherence. This multifaceted, patient-centered approach provides a roadmap for optimizing BP control, reducing cardiovascular risks, and addressing the complexities of hypertension in diverse populations. Full article

Background: Cardio-renal syndrome (CRS) is a complex condition involving bidirectional dysfunction of the heart and kidneys, in which the failure of one organ exacerbates failure in the other. Traditional pharmacologic treatments are often insufficient to manage the hemodynamic and neurohormonal abnormalities underlying CRS, especially in cases resistant to standard therapies. Device-based therapies have emerged as a promising adjunct or alternative approach, offering targeted intervention to relieve congestion, improve renal perfusion, and modulate hemodynamics. This study aimed to evaluate the efficacy and safety of various device-based therapies in CRS management, utilizing DRI2P2S classification to categorize interventions as dilators, reducers, interstitial modulators, pullers, pushers, and shifters. Methods: A comprehensive analysis of clinical trial data and observational studies involving device-based therapies in patients with CRS was conducted, with a focus on hemodynamic endpoints, renal and cardiac function, symptom relief, and adverse events. Devices included in the analysis were splanchnic denervation systems (dilators), devices for central and pulmonary pressure reduction (reducers), and systems targeting interstitial fluid (fluid shifters), among others. A systematic literature review from 2004 to 2024 was performed using databases including PubMed, Embase, and ClinicalTrials.gov, following PRISMA guidelines for study selection. Data were extracted on patient demographics, device type, trial design, outcomes, and follow-up duration. Results: Device-based therapies demonstrated varying levels of efficacy in CRS, with significant improvements observed in specific parameters. Notable results were a reduction in central venous pressure and improved diuretic responsiveness in acute CRS cases, while also stabilizing or improving renal function. Other relevant endpoints were fewer heart failure hospitalizations and a reduction in renal adverse events, reduced tissue congestion and improved quality of life scores. However, some devices presented challenges, including procedure-related complications and a learning curve for optimal device implantation. Conclusions: Device-based therapies offer a valuable addition to the CRS treatment paradigm, particularly in cases unresponsive to conventional diuretics and other pharmacologic measures. Each of them addresses specific pathophysiological components of CRS and shows promise in improving clinical outcomes. Nevertheless, further large-scale, long-term trials with comprehensive endpoints are needed to establish these therapies’ roles in standard care and to optimize patient selection criteria. Enhanced understanding of device mechanisms and refinement of trial endpoints will be key to maximizing the impact of these therapies on quality of life and clinical outcomes for CRS patients. Full article