AIMS:Radiofrequency (RF) renal denervation (RDN) safely lowers office and 24-h blood pressure (BP). This meta-analysis examined the long-term durability of RF RDN based on randomized trials and observational studies. METHODS AND RESULTS:Patients with uncontrolled hypertension undergoing RF RDN using the Symplicity Flex™ or Spyral™ device and a minimum follow-up of 3 years were included. Key outcomes included office and 24-h BP change from baseline as well as changes in anti-hypertensive drugs. A random effects meta-analysis was conducted over 3 years, or the last reported follow-up beyond 3 years. A total of 2212 patients identified among 18 reports were evaluated for BP. The mean duration of follow-up was 4.4 years (range 3-9.4). The long-term reduction in office systolic BP from baseline in 15 reports (n = 2040) was -23.0 mmHg (95% confidence interval: -26.8 to -19.1, P < 0.05) for the random effects model and -20.5 (-21.6 to -19.4) for the fixed effect model. Twenty-four-hour ambulatory systolic BP was available in 11 reports (n = 1018) and decreased significantly by -13.6 mmHg (-16.5 to -10.8, P < 0.05). Fixed effect model results were similar. Diastolic office and 24-h BP paralleled these findings in both models. Nighttime systolic BP also decreased significantly by -14.2 mmHg (-27.6 to -0.8, P < 0.05). The number of prescribed anti-hypertensive drugs and eGFR also decreased. Heart rate remained unchanged through the final follow-up in both models. Safety events were rare, with a mean rate of renal artery complications of 0.14% (0.08-0.20%). CONCLUSION:This meta-analysis comprising 18 studies demonstrated sustained and significant office and ambulatory BP reductions following Symplicity RDN through at least 3 years without an increase in anti-hypertensive medication.

BACKGROUND:Hypertension is the leading cause of premature death globally, and acute decompensated heart failure is among the most common causes of hospitalization. Both conditions are adversely affected by high dietary sodium intake. In contrast, potassium has been shown to lower blood pressure. Substituting dietary sodium with potassium may therefore reduce morbidity and mortality associated with hypertension and possibly heart failure. OBJECTIVES:This review summarizes the current evidence on the cardiovascular effects of dietary sodium and potassium-containing salts. CURRENT DATA:Epidemiological studies consistently demonstrate that high sodium intake is associated with elevated blood pressure and increased rates of cardiovascular morbidity and mortality. Meta-analyses indicate that reducing sodium intake lowers blood pressure and reduces cardiovascular events. In a cluster-randomized trial, partial substitution of sodium chloride with potassium-enriched salt reduced cardiovascular morbidity and mortality in patients with hypertension. However, robust data on the effects of sodium restriction or potassium substitution on hard cardiovascular outcomes in patients with heart failure remain limited. CONCLUSIONS:High sodium intake has detrimental effects on cardiovascular health. Substituting sodium with potassium-containing salts represents a promising strategy to reduce morbidity and mortality associated with hypertension.

BACKGROUND:Time in target range (TTR) reflects the proportion of time blood pressure (BP) remains within a defined range, integrating BP variability and control. We examined associations of systolic BP (SBP) TTR during ambulatory BP monitoring with cardiovascular and all-cause mortalities. METHODS:Patients from the Spanish Ambulatory BP Monitoring Registry who were receiving antihypertensive medications or who had sustained or masked hypertension without treatment, defined by office BP ≥140/90 mmHg and 24-hour BP ≥130/80 mmHg, were included. TTR was estimated by linear interpolation between consecutive SBP recordings obtained from ambulatory BP monitoring and expressed as the proportion of time SBP remained within 120 to 134 mm Hg during daytime and 110 to 119 mm Hg during nighttime, from which 24-hour TTR was derived. Associations with mortality were assessed by Cox regression adjusted for demographic and clinical variables. RESULTS:A total of 48 687 patients (46% women) were analyzed. Over a median follow-up of 9.7 years, 6502 deaths occurred, including 2185 cardiovascular deaths. Higher 24-hour TTR was associated with lower all-cause mortality (hazard ratio, 0.83 per 1-SD increment [95% CI, 0.80-0.85]). Similarly, higher 24-hour TTR was associated with lower cardiovascular mortality (hazard ratio, 0.80 per 1-SD increment [95% CI, 0.76-0.84]). Both associations remained significant after adjusting for the mean 24-hour SBP and SBP variability. CONCLUSIONS:Higher 24-hour SBP TTR derived from ambulatory BP monitoring was independently associated with lower all-cause and cardiovascular mortalities.

BACKGROUND:Sympathetic overactivity is associated with hepatic steatosis. Renal denervation (RDN) is an approved treatment for uncontrolled hypertension through sympathetic modulation; however, its hepatic effects are unknown. This study aimed to assess the effects of RDN on noninvasive tests for hepatic steatosis. METHODS:This single-center study included patients with uncontrolled hypertension and cardiometabolic comorbidities undergoing RDN (n=32) or a sham procedure (n=10). Noninvasive tests for hepatic steatosis, including the hepatic steatosis index (HSI) and fatty liver index (FLI), were calculated at baseline and follow-up visits. An external cohort from the UK Biobank was used to validate the correlation between proton density fat fraction magnetic resonance imaging scans of the liver and these surrogates. RESULTS:Compared with the control group, RDN significantly reduced HSI at 3 months (0.4±0.5 versus -1.3±0.3; P=0.009), 6 months (0.0±0.9 versus -2.6±0.5; P=0.027), and 12 months (0.0±0.6 versus -2.1±0.5; P=0.013), as well as FLI at 3 months (2.6±2.2 versus -3.8±1.2; P=0.021), 6 months (4.1±2.4 versus -5.7±1.2; P=0.002), and 12 months (2.0±2.7 versus -6.2±1.3; P=0.018). No significant differences were found in HSI (-1.9±0.7 versus -2.2±0.7; P=0.77) and FLI (-7.1±1.8 versus -5.3±1.7; P=0.49) between subjects in the intervention group whose office blood pressure decreased above or below the median of 19.5 mm Hg after 12 months. In the UK Biobank, correlation analysis showed a significant relationship between proton density fat fraction magnetic resonance imaging and HSI (r=0.40; P<0.0001) and FLI (r=0.27; P<0.0001). CONCLUSIONS:RDN significantly reduced HSI and FLI in patients with uncontrolled hypertension and cardiometabolic comorbidities, suggesting a potential role of sympathetic modulation in metabolic disorders.

The sympathetic nervous system (SNS) plays a critical role in regulating inflammatory responses after myocardial infarction (MI). We aimed to investigate whether modulation of the SNS through renal denervation (RDN) influences myocardial remodeling following MI. MI in rats was induced 2 days after bilateral RDN or Sham surgery. Cardiac MRI showed that left ventricular ejection fraction was significantly higher in RDN-treated MI rats compared to Sham-treated MI rats. RNA sequencing of left ventricular tissue revealed that RDN suppresses fibrosis and inflammation related pathways at the whole transcriptome level, with clear separation of the experimental groups. These findings were confirmed by histochemical, gene, and protein expression analyses, which found a significantly higher extent of fibrosis and CD206 expression in the MI rats compared to RDN-treated MI rats. To simulate SNS activity, PMA-differentiated THP-1 cells were incubated with the β-adrenoceptor agonist isoprenaline. This resulted in upregulation of profibrotic macrophage gene expression, which was not the case after co-stimulation with a β1-adrenoceptor antagonist. Modulation of the SNS through RDN mitigates left ventricular remodeling post-MI by reducing myocardial fibrosis and scar size. Heightened SNS activity promotes a profibrotic macrophage phenotype. These findings support investigation into the therapeutic potential of RDN for managing MI patients.

Angiographic signs of chronic thromboembolic pulmonary hypertension or disease (CTEPH/D) are frequently found during large-bore thrombectomy (LBT) in acute pulmonary embolism (PE). Data on the incidence of CTEPH/D signs and outcome after LBT are lacking. These angiographic signs are not equivalent to a confirmed diagnosis of CTEPH/D. To investigate the efficacy and safety of LBT in patients with acute PE and angiographic signs of CTEPH/D compared to patients without (N-CTEPH/D). In total, 250 patients from five centers (CTEPH/D = 98, N-CTEPH/D = 152) were retrospectively analyzed. Efficacy of LBT was assessed by comparing clinical, echocardiographic, and invasive data between the groups. Safety endpoints included periprocedural death, procedural complications, or bleeding defined as the need for blood transfusion or hemoglobin drop of at least 5 g/dl. At baseline, the CTEPH/D group had higher systolic pulmonary artery pressure (sPAP) (CTEPH/D: 54 ± 14 mmHg, N-CTEPH/D: 49 ± 13 mmHg, p = 0.006). After LBT, right ventricular/left ventricular-ratio (CTEPH/D: − 0.30 ± 0.26, N-CTEPH/D: − 0.27 ± 0.32, p < 0.001 for both), sPAP (CTEPH/D: − 13 ± 8, N-CTEPH/D: − 11 ± 8 mmHg, p < 0.001 for both), heart rate (CTEPH/D: − 19 ± 20 beats/min, N-CTEPH/D: − 21 ± 15 beats/min, p < 0.001 for both) and respiratory rate (CTEPH/D: − 6 ± 6 respirations/min, N-CTEPH/D: by − 8 ± 7 respirations /min, p < 0.001 for both) were significantly reduced in both groups without significant differences. Peri-interventional safety was comparable between groups. LBT appears to be safe and effective in patients with acute PE and angiographic signs of CTEPH/D. Long-term effects should be further investigated.

Large-bore mechanical thrombectomy (LBMT) is a catheter-directed therapy for acute pulmonary embolism (PE). The relationship between aspirated thrombus weight and volume with outcomes remains unclear. The aim was to evaluate the impact of aspirated thrombus weight and volume on outcomes after LBMT. This prospective, open-label, single-arm, single-center registry study included 48 patients undergoing LBMT using the FlowTriever system (Inari Medical/Stryker, Irvine, CA, USA). Thrombus weight and volume were quantified, and clot composition assessed. Associations between thrombus characteristics and clinical, invasive hemodynamics, echocardiographic parameters, and biomarkers were evaluated immediately after the procedure, at hospital discharge, and at 3-month follow-up. Thrombus material was available in 48 patients (31

Bluthochdruck ist die häufigste Ursache für vorzeitige Mortalität weltweit, während Dekompensationen bei Herzinsuffizienz zu den häufigsten Gründen für Krankenhausaufnahmen zählen. Beide Erkrankungen werden durch eine hohe Natriumaufnahme über Speisesalz und verarbeitete Lebensmittel begünstigt. Kalium wirkt hingegen blutdrucksenkend und könnte daher als Ersatz für Natrium in Speisesalzen verwendet werden, um dessen negativen Einfluss auf Hypertonie und Herzinsuffizienz zu reduzieren. In der vorliegenden Übersicht soll die aktuelle Evidenz zu den kardiovaskulären Effekten von natrium- und kaliumhaltigen Speisesalzen zusammengefasst werden. Epidemiologische Studien zeigen konsistent, dass eine hohe Natriumaufnahme mit erhöhtem Blutdruck und einer höheren Rate kardiovaskulärer Ereignisse assoziiert ist. Metaanalysen belegen zudem, dass eine Reduktion des Natriumkonsums zu einer Abnahme kardiovaskulärer Ereignisse beiträgt. In einer clusterrandomisierten Studie führte der teilweise Ersatz von natrium- durch kaliumhaltige Speisesalze bei arterieller Hypertonie zu einer Reduktion kardiovaskulärer Ereignisse und kardiovaskulärer Sterblichkeit. Robuste Daten zur Reduktion harter klinischer Endpunkte durch Natriumreduktion bei Herzinsuffizienz gibt es gegenwärtig nicht. Eine hohe Natriumaufnahme hat nachweislich negative Effekte auf die kardiovaskuläre Gesundheit. Der Ersatz von natrium- durch kaliumhaltige Speisesalze stellt daher einen vielversprechenden Ansatz dar, um die hohe Morbidität und Mortalität von Bluthochdruck zu mindern.

BACKGROUND:To explore associations of clinic and 24-hour ambulatory blood pressure (BP) monitoring (ABPM) with cardiovascular death (CVD), parameters were modeled for age and sex in this large cohort in primary care. METHODS:In the Spanish ABPM Registry, 59.124 patients had complete data on mortality, age, sex, and all ABPM. Office, mean, 24-hour, daytime, and nighttime systolic BP (SBP), diastolic BP, and pulse pressure (PP) were related to CVD according to age and sex and were modelled with restricted cubic splines to get trajectories. During a median of 9.7 years, 2361 patients had CVD (1229 males, 1132 females). RESULTS:Nonlinear relationships for office, 24-hour mean, daytime, and nighttime SBP, diastolic BP, and PP (P<0.0001 for all) for both sexes were observed. Until 75 years, SBP was higher in males than females, but differences were minimized after ≈60 to 70 years (P for interaction <0.0001). High SBP and PP are associated with CVD without heterogeneity between sexes and across aging. The increase of SBP and PP was higher at a higher age for females than males (P for interaction <0.0001). CVD was age-dependent, and ABPM, in particular nighttime BP did more closely associated with risk than office BP in younger than in older individuals. CONCLUSIONS:Twenty-four-hour mean, nighttime BP, and PP were closely associated with risk being higher in elderly females than males after 75 years, corresponding to a rise in BP in older females. Guidelines should continue to mandate the evaluation of 24-hour ABPM data for risk prediction.

BACKGROUND AND AIMS:Hypertension has a high prevalence in heart failure with preserved ejection fraction (HFpEF), which can be controlled, uncontrolled, or even resistant. The effects of empagliflozin on systolic blood pressure (SBP), time in target range, incidence of hypertensive urgencies, and studied cardiovascular and renal outcomes in different hypertension categories and after treatment with empagliflozin in the EMPEROR-Preserved trial were explored. METHODS:A total of 5533 patients were studied and the population was separated into resistant (resHTN), uncontrolled (uctrHTN), and controlled (ctrHTN) hypertension. The effect of SBP on outcomes and treatment effects of empagliflozin were explored. Analyses were done with Cox regression analyses adjusted for demographic and clinical confounders and with a mixed model for repeated measures. RESULTS:Empagliflozin reduced SBP in resHTN slightly more than in the other categories in the first weeks, while thereafter there were no significant differences. The modest reduction in SBP resulted in a moderate increase in time at target and reduced hypertensive urgencies. The primary endpoint was more prevalent in resHTN (P = .0358), but the treatment effect of empagliflozin on the primary endpoint was similar in resHTN, uctrHTN, and ctrHTN (P for interaction = .92) as was the improvement of the estimated glomerular filtration rate slope (P for interaction = .95) and change in quality of life by empagliflozin. CONCLUSIONS:In HFpEF, the prevalence of resHTN is high and is associated with frequently higher outcome rates compared with ctrHTN and uctrHTN. The treatment effect was not modified by hypertension categories. This indicates that in HFpEF, moderate modifications of blood pressure do not affect overall outcomes and treatment effects of empagliflozin.

BACKGROUND Renal denervation (RDN) lowers blood pressure (BP) in patients with uncontrolled hypertension. Current guidelines recommend RDN for patients with uncontrolled BP despite the use of antihypertensive (AH) medications. Durability of BP reductions and assessment of which patient baseline characteristics correlate with subsequent BP reductions are scarce. OBJECTIVES The authors leveraged patient data from the entire SYMPLICITY Clinical program to model long-term BP reductions and assess patient characteristics associated with future BP reductions. METHODS Repeated BP measurements from each patient were analyzed using linear mixed models. Models were fitted with office systolic BP (SBP), 24-h ambulatory SBP, office diastolic BP (DBP), and 24-h ambulatory DBP as outcome variables. Baseline BP, baseline number of AH medications, AH medications over time, and other variables were included as fixed effects. RESULTS The mixed model included data from 4,155 patients treated with the Symplicity RDN system. The mean age was 60 f 12 years, 40.4% of whom were female. Estimated, longitudinal office and 24-h ambulatory SBP changes through 36 months, after adjusting for AH medication effects, were biphasic, with a steep reduction after RDN through the first 6 months followed by continuous and steady reductions in office and 24-h SBP and DBP afterward through 36 months. Higher baseline office systolic or 24-h ambulatory SBP were correlated with greater reductions through follow-up in office and 24-h SBP, respectively. Patient characteristics consistent with high sympathetic nerve activity, such as atrial fibrillation and type 2 diabetes, emerged as statistically significant covariates associated with greater office systolic and office and 24-h diastolic BP reductions, respectively. CONCLUSIONS Modeling suggested patients have durable BP reductions following RDN, with a steep immediate reduction followed by a steady reduction through 3 years. (JA CC Adv. 2025;4:101606) (c) 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

BACKGROUND:Overactivity of the hepatic and renal sympathetic nerves is associated with chronic cardiovascular and metabolic conditions, including hypertension. AIMS:We studied the effect of combined renal and hepatic denervation through treatment of the common hepatic artery and the renal arteries. METHODS:Denervation was performed in the common hepatic artery and both renal arteries and their major branch vessels in normotensive swine using the same multielectrode radiofrequency (RF) ablation catheter (Symplicity Spyral). Renal and liver tissue samples were obtained for histological examination in two cohorts at 7 and 28 days post-procedure (n=5 sham, n=10 denervation for each timepoint). RESULTS:Combined hepatic and renal denervation was successfully achieved in all animals. At 7 days, the mean lesion depth was 5.8±1.4 mm in the renal arteries and 4.7±0.7 mm in the hepatic artery. Compared with controls, the mean renal cortical norepinephrine (NE) levels were reduced by 88.2% in the 7-day model and by 84.5% in the 28-day model. Liver NE decreased by 94.6% at 7 days and by 91.1% at 28 days (p<0.0001 for all comparisons with baseline). No inadvertent injury was detected in the treated arteries or adjacent tissues. CONCLUSIONS:Combined hepatic and renal denervation using the same multielectrode RF denervation system resulted in a substantial reduction in both renal and hepatic tissue NE levels that was sustained up to 28 days without collateral tissue injury. These mechanistic findings may have implications for the treatment of chronic diseases impacted by hepatic and renal sympathetic nervous system overactivity.

Renal denervation (RDN) is an interventional approach that targets the sympathetic nervous system with the goal of modulating its activity, an important contributor to the pathogenesis of many cardiovascular and metabolic diseases. Unlike pharmacologic therapies, RDN efficacy is independent of patient adherence to medications, which remains a major limiting factor in long-term blood pressure control. Initially developed to treat severe, treatment-resistant hypertension, RDN has demonstrated consistent results in recent sham-controlled trials across the spectrum of hypertension. As a result, RDN has been incorporated into European guidelines as a treatment option for select patients and endorsed by cardiovascular and hypertension societies worldwide. This review outlines the physiological rationale behind RDN, summarizes the current evidence supporting its effectiveness, provides an overview of the available technologies, and evaluates its emerging role in the treatment of chronic heart failure and other conditions characterized by high sympathetic nervous system activity. Finally, the authors explore future directions, including the concept of multiorgan denervation, which aims to achieve an enhanced degree of sympathetic modulation by targeting additional sympathetic nerves beyond the kidney.

The American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guideline has now released the long-awaited 2025 American College of Cardiology/American Heart Association Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Since the previous version, which had been in place for 8 years, meta-analyses and several treat-to-target trials investigating lower versus standard blood pressure targets have been published. Based on these, the 2025 American College of Cardiology/American Heart Association guideline recommends in adults with confirmed hypertension, an office blood pressure goal of <130/80 mm Hg, with encouragement to further reduce systolic blood pressure to <120 mm Hg. Here, we set out why we support these lower blood pressure targets and outline strategies to achieve them.

The objective of this study was to demonstrate the safety and efficacy of a novel cryo renal denervation system (Cryo-RDN) in a porcine model. Procedural and mid-term safety of the Cryo-RDN was demonstrated. Efficacy of the cryoablation was evidenced by histological findings in the renal arteries and reduced renal tissue norepinephrine concentrations on the treated sides. Despite some morphological nerve repair observed between 7 and 28 days, the greater renal norepinephrine suppression in the 28-day animals suggests irreversibly ablated sympathetic nerves.