Search Results (53)

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

Morning-time heart attacks are associated with an ablation in the sleep-time dip in blood pressure, the mechanism of which is unknown. The epigenetic changes are the hallmark of sleep and circadian clock disruption and homocystinuria (HHcy). The homocystinuria causes ablation in the dip in blood pressure during sleep. Interestingly, HHcy is generated during the epigenetic gene turning off and turning on (i.e., imprinting) by methylation of the DNA promoter. The mitochondrial sulfur metabolism by 3-mercaptopyruvate sulfur transferase (3MST), ATP citrate lyase (ACYL), and epigenetic rhythmic methylation are regulated by folate 1-carbon metabolism (FOCM), i.e., the methionine (M)-SAM-SAH-Hcy, adenosine, and uric acid cycle. Epigenetic gene writer (DNMT), gene eraser (TET/FTO), and editor de-aminase (ADAR) regulate the rhythmic, i.e., reversible methylation/demethylation of H3K4, H3K9, H4K20, m⁶A, and m⁵C. The mitochondrial ATP citrate cycle and creatine kinase (CK) regulate chromatin transcription, maturation, and accessibility as well as muscle function. The transcription is regulated by methylation. The maturation and accessibility are controlled by acetylation. However, it is unclear whether a high fat dysbiotic diet (HFD) causes dysrhythmic expression of the gene writer, eraser, and editor, creating hyperuricemia and cardiac and renal dysfunction. We hypothesized that an HFD increases the gene writer (DNMT1) and editor (ADAR), decreases the eraser (TET/FTO), and increases uric acid to cause chronic diseases. This increases the levels of H3K4, H3K9, H4K20, m⁶A, and m⁵C. Interestingly, the DNMT1KO mitigates. Further, the DNMT1KO and ADAR inhibition attenuate HFD-induced NGAL/FGF23/TMPRSS2/MMP2, 9, 13, and uric acid levels and improve cardiac and renal remodeling. Although the novel role of nerve endings by the Piezo channels (i.e., the combination of ENaC, VDAC, TRPV, K⁺, and Mg²⁺ channels) in the interoception is suggested, interestingly, we and others have shown mechanisms independent of the nerve, by interoception, such as the cargo of the exosome in denervation models of heart failure. If proper and appropriate levels of these enzymes are available to covert homocysteine to hydrogen sulfide (H₂S) during homocystinuria, then the H₂S can potentially serve as a newer form of treatment for morning heart attacks and renal sulfur transsulfuration transport diseases. Full article

Renal denervation (RDN), a transcatheter renal sympathetic nerve ablation procedure, is a relatively novel established procedure for the treatment of hypertension, with it being recognized as a third option for hypertension management in the most recent European guidelines, together with pharmacotherapy, for achieving blood pressure targets. Given the relationship between both hypertension and sympathetic overdrive and the development of heart failure (HF), even studies at the dawn of research on RDN explored it as a treatment to overcome diuretic resistance in those patients. As it is now recognized that RDN does not only have organ-specific but also systemic effects, several investigators have aimed to delineate whether renal sympathetic denervation could alter the prognosis, symptoms, and adverse events of HF patients. Data are available in both HF patients with reduced and preserved ejection fraction. As the significance of neuromodulation is gaining grounds in the HF therapeutic arsenal, in this review, we aim to provide a rationale for using RDN in HF and an up-to-date overview of available data in both HF phenotypes, as well as discuss the future of neuromodulatory therapy in HF management. Full article

Arterial hypertension remains the major cardiovascular risk worldwide. It is estimated that under 50 years of age one in every three adults is hypertensive while beyond the age of 50 the prevalence is almost 50% globally. The latest World Health Organization (WHO) Global Report on Hypertension indicated that the global number of hypertensive patients almost doubled in the last three decades, with related increasing deaths, disability, and costs annually. Because of this global increase, early diagnosis and timely treatment is of great importance. However, based on the WHO Global Report, it is estimated that up to 46% of individuals were never diagnosed. Of those diagnosed, less than 50% were on treatment, with nearly half among these at target according to the current guidelines. It is also important to note that an increasing number of hypertensive patients, despite the use of three or more drugs, still do not achieve a blood pressure normalization, thus defining the clinical scenario of resistant hypertension (RH). This condition is associated to a higher risk of hypertension-mediated organ damage and hospitalization due to acute cardiovascular events. Current guidelines recommend a triple combination therapy (renin angiotensin system blocking agent + a thiazide or thiazide-like diuretic + a dihydropyridinic calcium-channel blocker) to all patients with RH. Beta-blockers and mineralocorticoid receptor antagonists, alone or in combination, should be also considered based on concomitant conditions and potential contraindications. Finally, the renal denervation is also proposed in patients with preserved kidney function that remain hypertensive despite the use of maximum tolerated medical treatment. However, the failure of this procedure in the long term and the contraindication in patients with kidney failure is a strong call for a new therapeutic approach. In the present review, we will discuss the pharmacological novelties to come for the management of hypertension and RH in the next future. Full article

Heart failure (HF) is a significant global healthcare burden with increasing prevalence and high morbidity and mortality rates. The diagnosis and management of HF are closely tied to ejection fraction (EF), a crucial parameter for evaluating disease severity and determining treatment plans. This paper emphasizes the urgent need to maintain EF during heart failure, highlighting the distinct phenotypes of HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). It discusses the complexities of HFrEF pathophysiology and its negative impact on patient outcomes, stressing the importance of ongoing research and the development of effective therapeutic interventions to slow down the progression from preserved to reduced ejection fraction. Additionally, it explores the potential role of renal denervation in preserving ejection fraction and its implications for HFrEF management. This comprehensive review aims to offer valuable insights into the critical role of EF preservation in enhancing outcomes for patients with heart failure. Full article

The Goldblatt model of hypertension (2K-1C) in rats is characterized by renal sympathetic nerve activity (rSNA). We investigated the effects of unilateral renal denervation of the clipped kidney (DNX) on sodium transporters of the unclipped kidneys and the cardiovascular, autonomic, and renal functions in 2K-1C and control (CTR) rats. The mean arterial pressure (MAP) and rSNA were evaluated in experimental groups. Kidney function and NHE3, NCC, ENaCβ, and ENaCγ protein expressions were assessed. The glomerular filtration rate (GRF) and renal plasma flow were not changed by DNX, but the urinary (CTR: 0.0042 ± 0.001; 2K-1C: 0.014 ± 0.003; DNX: 0.005 ± 0.0013 mL/min/g renal tissue) and filtration fractions (CTR: 0.29 ± 0.02; 2K-1C: 0.51 ± 0.06; DNX: 0.28 ± 0.04 mL/min/g renal tissue) were normalized. The Na⁺/H⁺ exchanger (NHE3) was reduced in 2K-1C, and DNX normalized NHE3 (CTR: 100 ± 6; 2K-1C: 44 ± 14, DNX: 84 ± 13%). Conversely, the Na⁺/Cl⁻ cotransporter (NCC) was increased in 2K-1C and was reduced by DNX (CTR: 94 ± 6; 2K-1C: 144 ± 8; DNX: 60 ± 15%). In conclusion, DNX in Goldblatt rats reduced blood pressure and proteinuria independently of GRF with a distinct regulation of NHE3 and NCC in unclipped kidneys. Full article