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Background: Risk stratification of patients with right bundle branch block (RBBB) undergoing transcatheter aortic valve implantation (TAVI) remains challenging., Objective: To evaluate the European Society of Cardiology (ESC) criteria for risk stratification of RBBB patients undergoing TAVI., Methods: We retrospectively analyzed prospectively enrolled patients with pre-existing RBBB undergoing TAVI between 2011-2023. A surface 12-lead electrocardiogram was available before and after the procedure in all patients. The following ESC criteria were validated: ΔPR interval ≥20 ms, QRS axis change or transient high-degree atrioventricular block (HAVB) <24 hours after TAVI., Results: Pre-existing RBBB was documented in 107 out of 1,410 patients (7.6%) undergoing TAVI. Mean age was 83±5 years, 34% were female, and 66% received self-expandable valves. Of those 107 patients with pre-existing RBBB, 36 (34%) developed persistent HAVB lasting longer than 24 hours and received permanent pacemaker therapy. Among the remaining 71 patients, 16 patients (23%) developed delayed HAVB during 30-days of follow-up. The ESC criteria identified 81% of patients (13/16) with delayed HAVB during 30-day follow-up, while missing 3 patients (19%, 2.8% of the overall cohort). This resulted in a sensitivity of 81% and a negative predictive value of 92%. Meeting the ESC criteria bore a 6-fold increase in the odds of developing HAVB during 30-day follow-up (OR 6.5, 95%-CI 1.84-30.8, p = 0.007)., Conclusion: In this large cohort of patients with pre-existing RBBB undergoing TAVI with contemporary prosthesis and implantation techniques, the ESC criteria - PR prolongation, QRS axis change or transient HAVB - correctly identified 4/5 patients developing HAVB during 30-day follow-up., (Copyright © 2024. Published by Elsevier Inc.)

Background: Renal denervation lowers blood pressure (BP) in patients with uncontrolled hypertension. We conducted an unbiased genomic screen to identify genetic variants that may associate with BP response to renal denervation (RDN)., Methods: Patients (n=268) with uncontrolled resistant hypertension (baseline BP, 166±21/90±15 mm Hg) who underwent endovascular RDN using the Symplicity catheter (Medtronic, Inc, Santa Rosa, CA) were included. Reduction in 24-hour ambulatory systolic BP was assessed at 6 months and divided into 2 groups: above and below the median response of 6.0 mm Hg, taking preintervention 24-hour ambulatory BP and regression to the mean into account. Whole exome sequencing assessing 249 669 variants, was conducted using Illumina NovaSeq technology read on a NovaSeq S4 Flow Cell device., Results: We did not identify individual gene variants associated with BP response following RDN. These findings were confirmed after adjustment for sex and in a sensitivity analysis looking at tertiles of BP response. We also explored specific variants in AGT , ADD1 , ADRB1, ADRB2 , and SCNN1A that have been proposed as potential candidate genes for response and found no association (all P >0.13). Gene ontology analysis of variants across the 2 responder groups highlighted differences in biologic processes such as cell adhesion and molecular function such as protein tyrosine kinase activity., Conclusions: The response to RDN, in terms of 24-hour BP reduction, was not associated with the genetic profile of patients with resistant hypertension. These data do not support the use of a genetic score to identify potential responders to RDN.

Multiple sham-controlled clinical trials have demonstrated significant reductions in both office and 24-h blood pressure (BP) following radiofrequency renal denervation (RDN) in the uncontrolled hypertension population. Notably, the blood pressure response varies widely within individual participants, thus showing a clinical need to identify potential RDN "responders" prior to the procedure. Despite multiple analytic efforts, no single parameter, aside from baseline blood pressure, has been consistently associated with BP reduction following RDN. However, this failure may be due to limitations in empiric definitions of responders. Indeed, commonly applied responder definitions based on the difference between two point-in-time BP measurements are fraught due to visit-to-visit variability in office and 24-h blood pressure endpoints. Several factors should be considered to develop a more clinically useful operational definition of procedural response including relative changes in office and 24-h BP, consideration of the temporal response to RDN, as well as adjustment for baseline BP. The current evidence may provide incentives for future expert consensus to precisely define responders to hypertension treatments., Competing Interests: Compliance with ethical standards Conflict of interest RES reports grants and personal fees from Medtronic, Recor, and Ablative Solutions. DAH is a full-time employee of Medtronic, Inc. MB reports support from Astra-Zeneca, Bayer, BMS, Boehringer-Ingelheim, Glaxo, Medtronic, Novartis, ReCor, Servier and Vifor. MB is funded by the German Research Foundation (DFG, TTR 219, S-01, M-03, project number 322900939). DEK receives institutional research/grant support from Biotronik, Boston Scientific,. Orbus Neich, Teleflex, Medtronic, and Ablative Solutions; he also receives personal consulting honoraria from Medtronic and HyperQure. KK receives personal fees from Medtronic, receives grants from A&D Company, JIMRO, OmronHealthcare, CureApp, Terumo, and Fukuda Denshi, receives honoraria from Otsuka Pharmaceuticals and Omron Healthcare, and participates on the advisory board of Fukuda Denshi. FM is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219, Project-ID 322900939), and Deutsche Herzstiftung. Saarland University has received scientific support from Ablative Solutions, Medtronic and ReCor Medical. Until May 2024, FM has received speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. KT receives payments from Medtronic for work as centre principal investigator. MAW is a consultant for Medtronic, ReCor Medical, Ablative Solutions, Johnson & Johnson, and Urovant. MDE has received consulting fees and travel and research support from Medtronic. RET is a consultant for Medtronic, Axio, Regeneron, Bard, OBIO and AstraZeneca. Royalties from UpToDate., (© 2024. The Author(s).)

Background: Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes. We aimed to perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension., Methods: We searched MEDLINE and the Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data., Results: Ten trials comprising 2478 patients with hypertension while being either off or on treatment were included. Compared with sham, RDN reduced 24-hour and office systolic blood pressure by 4.4 mm Hg (95% CI, 2.7 to 6.1; P <0.00001) and 6.6 mm Hg (95% CI, 3.6 to 9.7; P <0.0001), respectively. The 24-hour and office diastolic blood pressure paralleled these findings (-2.6 mm Hg [95% CI, -3.6 to -1.5]; P <0.00001; -3.5 mm Hg [95% CI, -5.4 to -1.6]; P =0.0003). There was no difference in 24-hour and office systolic blood pressure reduction between trials with and without concomitant antihypertensive medication ( P for interaction, 0.62 and 0.73, respectively). There was no relevant difference in vascular complications (odds ratio, 1.69 [95% CI, 0.57 to 5.0]; P =0.34), renal artery stenosis (odds ratio, 1.50 [95% CI, 0.06 to 36.97]; P =0.80), hypertensive crisis (odds ratio, 0.65 [95% CI, 0.30 to 1.38]; P =0.26), and all-cause death (odds ratio, 1.76 [95% CI, 0.34 to 9.20]; P =0.50) between RDN and sham groups. Change of renal function based on estimated glomerular filtration rate was comparable between groups ( P for interaction, 0.84). There was significant heterogeneity between trials., Conclusions: RDN safely reduces ambulatory and office systolic blood pressure/diastolic blood pressure versus a sham procedure in the presence and absence of antihypertensive medications., Competing Interests: E.R.E. was supported in part by the National Institutes of Health (R01 HL161069). L.L. received speaker honoraria from AstraZeneca, Medtronic, Pfizer, and ReCor Medical until May 2024. F.M. is supported by Deutsche Gesellschaft für Kardiologie, Deutsche Forschungsgemeinschaft (SFB TRR219, Project-ID 322900939), and Deutsche Herzstiftung. Saarland University has received scientific support from Ablative Solutions, Medtronic, and ReCor Medical. Until May 2024, F.M. has received speaker honoraria/consulting fees from Ablative Solutions, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. D.L.B. discloses the following relationships: advisory board: Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, and Stasys; board of directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); consultant: Broadview Ventures, GlaxoSmithKline, Hims, SFJ, and Youngene; data monitoring committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial [Portico Re-sheathable Transcatheter Aortic Valve System], funded by St Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial [Pulmonary Embolism Thrombolysis]), Cleveland Clinic, Contego Medical (chair, PERFORMANCE 2 [Protection Against Emboli During Carotid Artery Stenting Using the Neuroguard IEP System]), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial [Edoxaban versus Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation–Atrial Fibrillation], funded by Daiichi Sankyo; for the ABILITY-DM trial [Randomized Comparison of Abluminus DES+ Sirolimus-Eluting Stents Versus Everolimus-Eluting Stents in Coronary Artery Disease Patients With Diabetes Mellitus Global], funded by Concept Medical; for ALLAY-HF [Evaluation of the Safety and Feasibility of a Percutaneously Created Interatrial Shunt to Alleviate Heart Failure Symptoms in Patients With Chronic Heart Failure and Preserved or Mid-Range Left Ventricular Ejection Fraction], funded by Alleviant Medical), Novartis, Population Health Research Institute, and Rutgers University (for the National Institutes of Health–funded MINT trial [Myocardial Ischemia and Transfusion]); honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; chair, ACC accreditation oversight committee), Arnold and Porter law firm (work related to Sanofi/Bristol Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial [Randomized Evaluation of Dual Antithrombotic Therapy With Dabigatran versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention] steering committee funded by Boehringer Ingelheim; AEGIS-II [ApoA-I Event Reducing in Ischemic Syndromes II] executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial [A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease], funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor; associate editor), K2P (co-chair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), and Wiley (steering committee); other: Clinical Cardiology (deputy editor); patent: sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither I nor Brigham and Women’s Hospital receives any income from this patent); research funding: Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio; royalties: Elsevier (editor, Braunwald’s Heart Disease); site coinvestigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; trustee: American College of Cardiology; and unfunded research: FlowCo. R.E.S. received speaker and advisor honoraria from Ablative Solutions, Medtronic, and Recor and grants to the institution from Ablative Solution, Medtronic, and Recor. D.E.K. discloses the following relationships: personal consulting honoraria: Medtronic, Ablative Solutions, and HyperQure; institutional research/grant support: Ablative Solutions, Biotronik, Medtronic, Orchestra Biomed, Orbus Neich, and Teleflex; and equity: BioStar Ventures (none related to Ablative Solutions). M.B. is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project No. 322900939) and reports personal fees from Abbott, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Edwards, Medtronic, Novartis, Recor, Servier, and Vifor. M.A. reports receiving grants from the European Horizon 2020 program; grants from Recor Medical, Idorsia, Novartis, and AstraZeneca; and personal fees from Alnylam Pharmaceuticals, Recor Medical Cincor, Medtronic, AstraZeneca, and Novartis. The other authors report no conflicts.

Background: Renal denervation (RDN) can lower blood pressure (BP) in patients with hypertension in both the presence and absence of medication. This is a sham-controlled trial investigating the safety and efficacy of RDN in China., Methods: This prospective, multicenter, randomized, patient- and outcome-assessor-blinded, sham-controlled trial investigated radiofrequency RDN in patients with hypertension on standardized triple antihypertensive therapy. Eligible patients were randomized 1:1 to undergo RDN using a multi-electrode radiofrequency catheter (Iberis; Shanghai Angiocare Medical Technology, Shanghai, China) or a sham procedure. The primary efficacy outcome was the between-group difference in baseline-adjusted change in mean 24-hour ambulatory systolic BP from randomization to 6 months., Results: Of 217 randomized patients (mean age, 45.3±10.2 years; 21% female), 107 were randomized to RDN and 110 were randomized to sham control. At 6 months, there was a greater reduction in 24-hour systolic BP in the RDN (-13.0±12.1 mm Hg) compared with the sham control group (-3.0±13.0 mm Hg; baseline-adjusted between-group difference, -9.4 mm Hg [95% CI, -12.8 to -5.9]; P <0.001). Compared with sham, 24-hour diastolic BP was lowered by -5.0 mm Hg ([95% CI, -7.5 to -2.4]; P <0.001) 6 months after RDN, and office systolic and diastolic BP was lowered by -6.4 mm Hg ([95% CI, -10.5 to -2.3]; P =0.003) and -5.1 mm Hg ([95% CI, -8.2 to -2.0]; P =0.001), respectively. One patient in the RDN group experienced an access site complication (hematoma), which resolved without sequelae. No other major device- or procedure-related safety events occurred through follow-up., Conclusions: In this trial of Chinese patients with uncontrolled hypertension on a standardized triple pharmacotherapy, RDN was safe and reduced ambulatory and office BP at 6 months compared with sham., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02901704., Competing Interests: X. Jiang is supported by Iberis-HTN trial fund from Shanghai Angiocare Medical Technology, CAMS Innovation Fund for Medical Sciences (grant Nos. 2021-I2M-C&T-B-026 and 2021-I2M-C&T-B-027). He has received speaker honoraria fees from Medtronic and Terumo. Felix Mahfoud is supported by Deutsche Gesellschaft für Kardiologie, Deutsche Forschungsgemeinschaft (SFB TRR219, Project ID 322900939), and Deutsche Herzstiftung. He has received scientific support from Ablative Solutions, Medtronic, and ReCor Medical, and speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. L. Lauder received speaker honoraria/consulting fees from AstraZeneca, Medtronic, Pfizer, and ReCor. Brad Hubbard is an employee of EastPoint Innovation Center. X. Hu is an employee of Shanghai Angiocare Medical Technology. R. Gao received institutional research grants from Shanghai Angiocare Medical Technology (Shanghai, China) and Biotyx Medical (Shenzhen, China). The remaining authors report no conflicts of interest related to this article.

Pulmonary vein isolation (PVI) has been established as a first-line therapy for symptomatic atrial fibrillation (AF) in selected patients with symptomatic AF and in those whose antiarrhythmic drug treatment failed. However, AF recurrence rates after PVI remain high, prompting the exploration of adjunct therapies, such as renal denervation (RDN), to improve outcomes. This meta-analysis aimed to assess the efficacy of RDN as an adjunct to PVI in reducing AF recurrence. A comprehensive search of randomized controlled trials comparing RDN plus PVI with PVI alone was conducted, yielding 9 studies with 955 patients. The primary end point was freedom from AF at 12 months. The results showed that 61.7% of patients in the RDN+PVI group were free from AF compared with 52.6% in the PVI alone group (risk ratio 1.32, 95% confidence interval 1.07 to 1.61, I² = 48%). These findings support the potential of RDN to enhance PVI efficacy; however, further large-scale randomized controlled trials with standardized methods and longer follow-up periods are necessary to confirm these results and establish the role of RDN in the treatment of AF., Competing Interests: Declaration of competing interest Dr. Kresoja has received travel support and consulting fees from Edwards Lifesciences. Prof. Mahfoud is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219, Project-ID 322900939), and Deutsche Herzstiftung. Saarland University has received scientific support from Ablative Solutions, Medtronic (Milestone), and ReCor Medical. Until May 2024, FM has received speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. Prof. Lurz has received institutional fees and research grants from Abbott Vascular, Edwards Lifesciences, and ReCor, honoraria from Edwards Lifesciences, Abbott Medical, Innoventric, ReCor, and Boehringer Ingelheim and has stock options with Innoventric. Prof. Piccini is supported by R01AG074185 from the National Institutes of Aging. He also receives grants for clinical research from Abbott, the American Heart Association, Boston Scientific, iRhythm, and Philips and serves as a consultant to ABVF, Abbott, AbbVie, Boston Scientific, ElectroPhysiology Frontiers, Kardium, Medtronic Pharmaceuticals, Pacira, Sanofi, Philips, and Up-to-Date. Dr. Fudim has received consulting fees from Medtronic, ReCor, and SyMap. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Activation of the sympathetic nervous system has been attributed to the development of hypertension. Two established approaches for treating hypertension are pharmacotherapy and lifestyle changes. With an improved understanding of renal nerve anatomy and physiology, renal denervation has been proposed as an alternative treatment for hypertension. Specifically, it has been shown that the interruption of sympathetic nerves connecting the kidney and the sympathetic nervous system can reduce blood pressure. Here, we present a review on how renal denervation can help hypertension patients, specifically focusing on our novel understanding of renal nerve anatomy, denervation technique, and subsequent clinical trials, and how it may be used to treat other cardiovascular diseases like heart failure., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Paclitaxel-coated balloons (PCB) are a viable alternative to drug-eluting stents in the treatment of de novo coronary lesions. Whether sirolimus represents an alternative to paclitaxel for drug-coated balloons remains elusive., Aims: This randomised, controlled, multicentre, non-inferiority trial investigated a novel sirolimus-coated balloon (SCB) with a crystalline coating versus a PCB in de novo coronary lesions., Methods: To compare a novel SCB with a clinically proven PCB, 70 patients with de novo coronary lesions were enrolled at 4 centres in Germany and Switzerland. The primary endpoint was non-inferiority regarding angiographic late lumen loss (LLL) at 6 months, with a predefined margin of δ=0.35 mm. Secondary endpoints included procedural success, major adverse cardiac events, and individual clinical endpoints., Results: Quantitative coronary angiography revealed no differences in baseline parameters. At 6 months, in-segment LLL was 0.04±0.39 mm in the PCB group versus 0.11±0.37 mm in the SCB group (non-significant), respectively. The mean difference between SCB and PCB was 0.07 mm (95% confidence interval: -0.12 to 0.26). Non-inferiority at the predefined margin of 0.35 was shown. Clinical event rates up to 12 months were not different between the groups (3 target lesion revascularisations in the PCB group versus 2 in the SCB group, no myocardial infarctions, no deaths)., Conclusions: The novel SCB showed similar angiographic outcomes in the treatment of de novo coronary disease as compared with a clinically proven PCB (ClinicalTrials.gov: NCT03908450).

Objectives: Because angiotensin (Ang) II is an essential vasoconstrictive peptide, we analyzed the impact of its post-translational modification to pyruvamide-Ang II (Ang P) by pyridoxal-5'-phosphate (PLP) on blood pressure. PLP is a less expensive vitamin B 6 derivative and, therefore, could be a cost-effective drug against hypertension., Methods: Effect of Ang P on calcium ion entry into vascular smooth muscle cells (VSMCs) was analyzed. Binding affinity of Ang P to angiotensin II type 1 receptor (AT 1 R) was measured. Vasoconstrictive effect of Ang P was investigated using the bioassay of isolated perfused rat kidneys. Spontaneously hypertensive rats (SHR) were administered PLP. Additionally, Wistar Kyoto rats (WKY) received Ang II and PLP. Blood pressure was measured time-dependently., Results: Ang II, incubated with PLP, was post-translationally modified to Ang P. Calcium ion entry in VSMCs was significantly lower with Ang P compared to Ang II. Binding affinity of Ang P to AT 1 R was lower compared to Ang II. Perfusion pressure of isolated perfused rat kidneys increased less by Ang P than by Ang II. Blood pressure of SHR treated with PLP decreased significantly. Blood pressure of WKY rats treated with Ang II was increased to hypertensive values, whereas blood pressure of WKY rats cotreated with Ang II and PLP was not., Conclusion: PLP induces a post-translational modification of Ang II decreasing blood pressure in rats. Assuming that increased PLP intake in the form of vitamin B 6 might reduce blood pressure in hypertensive patients, PLP might be a cost-effective drug against hypertension., (© 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Arterial hypertension remains the most important modifiable cardiovascular risk factor for morbidity and mortality worldwide. This review summarizes and discusses major clinical trials published in 2023 and early 2024 in hypertension research. These trials include new epidemiological data, studies investigating the impact of blood pressure cuff size on blood pressure measurements, benefits of salt substitutes, and novel antihypertensive treatment options, including pharmacotherapy and bariatric surgery in patients with obesity. This summary reviews the major clinical trials published in 2023 and early 2024. AHT arterial hypertension, BP blood pressure, HR hazard ratio, OBP office blood pressure, PRA plasma renin activity, SBP systolic blood pressure., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Catheter-based renal sympathetic denervation (RDN) reduced blood pressure (BP) in multiple randomized sham-controlled trials of patients with uncontrolled hypertension (HTN). We tested proof-of-concept for a more selective treatment strategy, exclusively targeting these areas to improve the efficiency of the procedure., Methods: The SPYRAL DYSTAL Pilot study was designed to mirror the SPYRAL HTN-OFF MED Pivotal study, enabling comparison with a propensity score adjusted active-control group. Patients were antihypertensive medication-free for one month before undergoing BP assessment. Those with office BP of 150-180/>90 mmHg and with an ambulatory systolic BP of 140-170 mmHg were selected to undergo open label treatment, delivering energy only to the distal main renal arteries and first order branches. Patients from DYSTAL were compared with patients who underwent maximized RF RDN treatment in the prior randomized OFF MED trial at 3 months. After 3 months, patients resumed antihypertensive medications as indicated. Safety and efficacy outcomes were assessed post hoc through 12 months., Results: The SPYRAL DYSTAL Pilot study treated 56 HTN patients. Baseline office systolic BP (OSBP) and 24-h ambulatory systolic BP (ASBP) were similar between DYSTAL and OFF MED patient groups. The number of ablations (32.3 ± 8.0 vs 46.6 ± 15.3, p < 0.001), procedure time (67 ± 21 min vs 99 ± 36 min; p < 0.001), and contrast volume (173 ± 77 cc vs 208 ± 96 cc; p = 0.014) were significantly lower with the simplified treatment strategy. OSBP and ASBP changes compared with baseline were -9.0 and -1.4 mmHg at 3 months, -20.3 and -13.9 mmHg at 6 months, and -20.3 and -16.6 mmHg at 12 months, respectively. During the medication up-titration phase, BP reductions among DYSTAL patients were similar to reductions observed in OFF MED through 12 months, with comparable number of drugs (1.4 and 1.5 medications, respectively (P=NS)). Two adverse events related to guidewire placement were reported., Conclusion: In this pilot study, focusing ablation treatment on the distal main and proximal branch renal arteries was performed, resulting in fewer RF lesions, and reduced contrast volume and procedure time. Whether BP reductions are similar between a selective vs. maximized RDN approach requires further prospective study., Competing Interests: Declaration of competing interest Dr. Sharp receives personal fees from Medtronic, Boston Scientific, ReCor Medical, Penumbra and Philips, all outside the submitted work. Dr. Kandzari discloses receives institutional research/grant support from Biotronik, Boston Scientific, Orbus Neich, Teleflex, Medtronic, and Ablative Solutions; he also receives personal consulting honoraria from Medtronic and HyperQure. Dr. Townsend is a consultant for Medtronic, Cytel, and Janssen. Dr. Kario receives personal fees from Medtronic, receives grants from A&D Company, JIMRO, Omron Healthcare, CureApp, Terumo, and Fukuda Denshi, receives honoraria from Otsuka Pharmaceuticals and Omron Healthcare, and participates on the advisory board of Fukuda Denshi outside the submitted work. Dr. Mahfoud is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219, Project-ID 322900939), and Deutsche Herzstiftung. His institution (Saarland University) has received scientific support from Ablative Solutions, Medtronic and ReCor Medical. He has received speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. Dr. Weber receives consulting fees from Medtronic, ReCor Medical, Ablative Solutions, Johnson and Johnson, and Urovant. Dr. Schmieder receives grants and personal fees from Medtronic, ReCor Medical, and Ablative Solutions. Dr. Tsioufis receives institutional grant support from Medtronic and ReCor Medical, receives personal consulting honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, ReCor Medical, Servier, WinMedica, and ELPEN. Dr. Pocock receives personal fees from Medtronic outside this submitted work. Dr. Böhm is supported by the Deutsche Forschungsgemeinshaft (SFB TTR219), receives personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, ReCor Medical, Servier, and Vifor. Dr. Choi receives consulting fees from Medtronic outside this submitted work. Dr. Liu is an employee of Medtronic. Dr. Lee receives grants and serves on the advisory board for Medtronic outside this submitted work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Ultrasound renal sympathetic denervation (uRDN) reduces blood pressure (BP) in the absence and presence of antihypertensive treatment at 2 months. Beyond 3 years, there is a lack of follow-up data. This study investigated the long-term safety and efficacy of uRDN., Methods: This prospective observational study recruited patients previously included in the international multicenter ACHIEVE study, with office systolic blood pressure (SBP) ≥160 mmHg, 24 h ambulatory SBP ≥130 mmHg, ≥3 antihypertensive drugs and estimated Glomerular Filtration Rate (eGFR) ≥45 ml/min/1.73m 2 undergoing uRDN. The primary efficacy outcome was 24 h ambulatory SBP, adjusted for the number of defined daily dosages (DDD) of antihypertensive drugs. Statistical analyses were performed using linear mixed-effects models and inverse probability weighting., Results: A total of 27 out of the initially enrolled 96 patients underwent prospective follow-up at a median of 8.2 [7.6-8.9] years. Mean age was 62.6±9.3 years (37.0% female). Preprocedural 24 h ambulatory BP was 151.9/84.1±11.5/11.1 mmHg and the median number of DDDs was 5.0 [4.3-7.0]. At 8 years after uRDN, the change in 24 h ambulatory SBP was -19.5 [95%CI -26.7,-12.4] mmHg (p<0.001). The 8-year change in the number of DDDs was -1.7 [-2.8,-0.6] (p = 0.003). The 8-year decline in eGFR was -8.9 [-13.2,-4.7] ml/min/1.73m 2 (p<0.001). Clinical event data were available for all 96 patients (median follow-up 3.5 [1.0-8.0] years). Renal failure occurred in one patient and no cases of renal artery stenosis were detected., Conclusions: A significant BP reduction was observed up until 8 years following uRDN in parallel to a decrease in drug burden over time, in the absence of procedure-related adverse events., (© 2024. The Author(s).)

Steroidal mineralocorticoid receptor antagonists (MRAs) bind to the mineralocorticoid receptor and antagonize the effects of aldosterone, which contributes to the development and progression of cardio- and renovascular diseases. Guidelines recommend steroidal MRAs in patients with heart failure with reduced or mildly reduced ejection fraction, as they reduce morbidity and mortality. In heart failure with preserved ejection fraction, MRAs have not convincingly shown to improve prognosis. Steroidal MRAs delay the progression of chronic kidney disease, reduce proteinuria and lower blood pressure in resistant hypertension but can induce hyperkalaemia. Due to their limited selectivity to the mineralocorticoid receptor, steroidal MRAs can cause significant adverse effects, i.e. libido loss, erectile dysfunction, gynaecomastia, and amenorrhoea, leading to low rates of persistance. Against this background, new avenues for developing non-steroidal, selective (ns)MRAs and aldosterone-synthase inhibitors have been taken. Finerenone has been shown to delay the progression of diabetic nephropathy and lower the incidence of heart failure hospitalizations in patients with chronic kidney disease and diabetes compared with placebo. Finerenone has therefore been recommended by the 2023 European Society of Cardiology Guidelines for the management of diabetes in patients with type 2 diabetes and chronic kidney disease. Further randomized controlled trials assessing the safety and effectiveness of finerenone in patients with heart failure are currently ongoing. Esaxerenone provides antihypertensive effects and has been approved for the treatment of hypertension in Japan. Baxdrostat and lorundostat, novel selective aldosterone-synthase inhibitors, are currently under investigation. In phase II trials, baxdrostat and lorundostat were safe and effective in lowering blood pressure in resistant hypertension. In this review, we summarize and critically discuss the evidence for new drugs mitigating aldosterone in heart failure, hypertension, and chronic kidney disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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., Competing Interests: None.

Background: Randomized sham-controlled trials have confirmed the efficacy and safety of catheter-based renal denervation in hypertension. Data on the very long-term effects of renal denervation are scarce., Aims: This study evaluates the 10-year safety and efficacy of renal denervation in resistant hypertension., Methods: This prospective single-center study included patients with resistant hypertension undergoing radio-frequency renal denervation between 2010 and 2012. Office blood pressure, 24-h ambulatory blood pressure, antihypertensive medication, color duplex sonography, and renal function were assessed after 1-, 2- and 10-years., Results: Thirty-nine patients completed the 10-year follow-up (mean follow-up duration 9.4 ± 0.7 years). Baseline office and 24-h ambulatory systolic blood pressure were 164 ± 23 mmHg and 153 ± 16 mmHg, respectively. After 10 years, 24-h ambulatory and office systolic blood pressure were reduced by 16 ± 17 mmHg (P < 0.001) and 14 ± 23 mmHg (P = 0.001), respectively. The number of antihypertensive drugs remained unchanged from 4.9 ± 1.4 to 4.5 ± 1.2 drugs (P = 0.087). The estimated glomerular filtration rate declined within the expected range from 69 (95% CI 63 to 74) to 60 mL/min/1.73m 2 (95% CI 53 to 68; P < 0.001) through 10-year follow-up. Three renal artery interventions were documented for progression of pre-existing renal artery stenosis in two patients and one patient with new-onset renal artery stenosis. No other adverse events were observed during the follow-up., Conclusion: Renal denervation was safe and sustainedly reduced ambulatory and office blood pressure out to 10 years in patients with resistant hypertension., (© 2024. The Author(s).)

Aims: Clinical guidelines support the use of fixed-dose combinations (FDC) for prevention of cardiovascular disease. Implementation of FDC into clinical care remains challenging, and current population-based data are scarce., Methods and Results: Claims data on dispensed drugs in an outpatient care setting of approximately 87% of the German population were analysed regarding the use of FDC according to time, age of the insured persons, and active ingredients. The overarching trend for all FDC revealed a decrease from 77.3 defined daily doses per 1000 statutory health-insured (SHI) persons per day (DID) in the second half-year of 2018 (2018HY02) to 60.8 DID in the first half-year of 2023 (2023HY01) (Spearman ρ = -0.988; P  < 0.001). The total DID for all antihypertensives (AHT) increased from 590.6 in 2018HY02 to 624.8 in 2023HY01 (ρ = 0.855; P  = 0.002), but the DID for fixed-dose AHT (AHT-FDC) declined from 74.1 in 2018HY02 to 55.0 in 2023HY01 (ρ = -0.988; P  < 0.001). Conversely, the use of all lipid-lowering agents (LLA) and LLA-FDC continuously increased: The total DID of all LLA rose from 92.5 in 2018HY02 to 134.4 in 2023HY01 (ρ = 1.000; P  = 0.000), and for LLA-FDC from 3.1 in 2018HY02 to 5.5 DID in 2023HY01 (ρ = 0.915; P  < 0.001). AHT-FDC and LLA-FDC were less frequently dispensed to patients at least 80 years than to patients less than 80 years. Dispensing of multiple purpose FDC increased from 2018HY02 to 2023HY01 from 0.11 DID to 0.26 DID (ρ = 1.000; P  = 0.000) but remained negligible., Conclusion: Use of AHT-FDC in Germany is declining. In contrast, FDC containing LLA are increasingly prescribed. Dispensing of multiple purpose FDC is very low. Strategies are needed to facilitate the use of FDC as recommended by current guidelines., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hypertension is a major public health issue due to its association with cardiovascular disease risk. Despite the availability of effective antihypertensive drugs, rates of blood pressure (BP) control remain suboptimal. Renal denervation (RDN) has emerged as an effective non-pharmacological, device-based treatment option for patients with hypertension. The multicenter, single-arm, observational Global Paradise™ System (GPS) registry has been designed to examine the long-term safety and effectiveness of ultrasound RDN (uRDN) with the Paradise System in a large population of patients with hypertension., Methods: The study aims to enroll up to 3000 patients undergoing uRDN in routine clinical practice. Patients will be recruited over a 4-year period and followed for 5 years (at 3, 6, and 12 months after the uRDN procedure and annually thereafter). Standardized home BP measurements will be taken every 3 months with automatic upload to the cloud. Office and ambulatory BP and adverse events will be collected as per routine clinical practice. Quality-of-Life questionnaires will be used to capture patient-reported outcomes., Conclusions: This observational registry will provide real-world information on the safety and effectiveness of uRDN in a large population of patients treated during routine clinical practice, and also allow for a better understanding of responses in prespecified subgroups. The focus on home BP in this registry is expected to improve completeness of long-term follow-up and provide unique insights into BP over time., (© 2023. The Author(s).)

Endovascular ultrasound renal denervation (uRDN) reduced blood pressure (BP) compared to sham at 2 months in patients with resistant hypertension in the multicenter, blinded, randomized, sham-controlled RADIANCE-HTN TRIO trial. This analysis evaluates longer-term outcomes of patients randomized to uRDN. Patients with resistant hypertension to a 3-drug combination pill were randomized to uRDN (n = 69) or sham (n = 67). From 2-5 months, patients followed a standardized anti-hypertensive medication (AHM) titration protocol. At 6 months, patients were unblinded and received AHM per standard of care. In the uRDN group, 71% (49/69) completed 36-month follow-up. Screening office BP was 159/103 on 3.9 AHM. Baseline office BP on the single-pill combination was 153/99 mmHg. At 36 months, office BP changed by -14.5 ± 26.1/-9.0 ± 14.8 mmHg from screening (p < 0.001 for both) and -8.0 ± 24.5/-5.0 ± 14.6 mmHg from baseline (p = 0.007; p = 0.022) on 3.7 AHM. The efficacy of uRDN was durable to 36 months in patients with resistant hypertension with no safety concerns., (© 2024. The Author(s).)

The human microbiome emerges as a promising reservoir for diagnostic markers and therapeutics. Since host-associated microbiomes at various body sites differ and diseases do not occur in isolation, a comprehensive analysis strategy highlighting the full potential of microbiomes should include diverse specimen types and various diseases. To ensure robust data quality and comparability across specimen types and diseases, we employ standardized protocols to generate sequencing data from 1931 prospectively collected specimens, including from saliva, plaque, skin, throat, eye, and stool, with an average sequencing depth of 5.3 gigabases. Collected from 515 patients, these samples yield an average of 3.7 metagenomes per patient. Our results suggest significant microbial variations across diseases and specimen types, including unexpected anatomical sites. We identify 583 unexplored species-level genome bins (SGBs) of which 189 are significantly disease-associated. Of note, the existence of microbial resistance genes in one specimen was indicative of the same resistance genes in other specimens of the same patient. Annotated and previously undescribed SGBs collectively harbor 28,315 potential biosynthetic gene clusters (BGCs), with 1050 significant correlations to diseases. Our combinatorial approach identifies distinct SGBs and BGCs, emphasizing the value of pan-body pan-disease microbiomics as a source for diagnostic and therapeutic strategies., (© 2024. The Author(s).)

Aims: To investigate the changes in retinal microvasculature by contemporary imaging techniques during episodes of acute decompensated heart failure (ADHF) and following recompensation compared to age-matched controls without known cardiac or retinal disease., Methods and Results: Adult patients hospitalized with a primary diagnosis of ADHF, regardless of left ventricular ejection fraction (LVEF) and treated with a minimum dose of 40 mg of intravenous furosemide or equivalent were included. Transthoracic echocardiography was conducted in all patients. Eye examinations were performed out within the initial 24 h after admission and after recompensation before discharge. All eyes underwent a general examination, including a best corrected visual acuity test, dilated fundoscopy, spectral-domain optical coherence tomography (OCT) as well as OCT angiography (OCT-A). In addition, 40 participants without documented cardiac or retinal diseases served as controls. Forty patients with ADHF (mean age 78.9 ± 8.8 years; 32% female) with a mean LVEF of 43 ± 12.8% were included. All patients were treated with intravenous diuretics for a median of 4.3 ± 2.8 days. There was a significant reduction in N-terminal pro-B-type natriuretic peptide from baseline up to discharge (10 396 [interquartile range 6410] vs. 6380 [interquartile range 3933] pg/ml, p ≤ 0.001) and inferior vena cava diameters (2.13 ± 0.4 vs. 1.63 ± 0.3 cm, p = 0.003). Compared to the control group, patients with ADHF showed on admission impaired visual acuity (0.15 ± 0.1 vs. 0.35 ± 0.1 logMAR, p < 0.001), reduced macular vessel density (18.0 ± 1.9 vs. 14.3 ± 3.6 mm/mm 2 , p < 0.001) and perfusion density (42.6 ± 3.2 vs. 35.2 ± 9.7%, p < 0.001). After recompensation, the mean overall vessel density and mean overall perfusion density were markedly increased at discharge (14.3 ± 3.6 vs. 19.7 ± 2.6 mm/mm 2 , p = 0.001, and 35.2 ± 9.7 vs. 39.2 ± 6.5%, p = 0.005, respectively). The mean diameter of the superior temporal retinal vein at admission was significantly larger compared to the control group (136 ± 19 vs. 124 ± 22 μm, p = 0.008) and decreased significantly to 122 ± 15 μm at discharge (p < 0.001)., Conclusion: This analysis revealed a remarkable reversible change in retinal microvasculature after ADHF. This could provide a valuable evidence for use of OCT-A in the assessment of overall microperfusion and haemodynamic status in patients with acute heart failure., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Exhaled breath (EB) aerosol was in principle shown to be a suitable matrix for bioanalysis of volatile but also non-volatile compounds. This attracted particular interest in the field of drug analysis. However, a big gap still exists in the understanding how and which drugs and/or their metabolites are excreted into exhaled breath and could thus actually be detected. The current study aimed to develop an analytical workflow for the qualitative detection of non-volatile drugs in EB aerosol microparticles., Results: The analyte selection covered different drug classes such as antihypertensives, anticonvulsants or opioid analgesics to investigate and understand the excretion of drugs and their metabolites into EB aerosol. A device for collecting aerosol particles from the lung through impaction was used for the non-invasive sampling procedure. Three expiration cycles per participant and device were collected. The sample preparation consisted of a collector extraction with methanol. Qualitative method development and validation were performed using reversed-phase liquid chromatography (LC) coupled to orbitrap-based high-resolution mass spectrometry (HRMS). Qualitative method validation was done according to published recommendations and international guidelines. Parameters such as selectivity, carry-over, limits of detection and identification, recovery, matrix effects, and long-term stability were evaluated. The limits of detection ranged from 100 pg/collector to 10,000 pg/collector. The procedure was finally used to analyze a total of 31 patient EB samples and demonstrated that e.g., tilidine and its metabolite nortilidine as well as tramadol and its active metabolite O-desmethyltramadol can be detected in EB aerosol., Significance and Novelty: The work shows a comprehensive workflow for elucidating drug excretion into exhaled breath aerosol. This bioanalytical strategy and the corresponding novel data from this study are the foundation for further method development and to better understand, which drugs and their metabolites can be addressed by exhaled breath aerosol bioanalysis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Felix Mahfoud reports financial support was provided by German Research Foundation. Felix Mahfoud reports financial support was provided by German Cardiac Society. Felix Mahfoud reports financial support was provided by German Heart Foundation. Felix Mahfoud reports a relationship with Ablative Solutions, Medtronic, ReCor Medical, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Merck, Servier, and Terumo that includes: consulting or advisory and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: A detailed understanding of the sympathetic innervation of coronary arteries is relevant to facilitate the development of novel treatment approaches., Aims: This study aimed to quantitatively examine periarterial innervation in human epicardial coronary arteries., Methods: Coronary arteries with adjacent epicardial adipose tissue were excised along the left main coronary artery (LMCA), left anterior descending artery (LAD), left circumflex artery (LCx), and right coronary artery (RCA) from 28 body donors and examined histologically. Immunofluorescence staining was performed to characterise sympathetic nerve fibres., Results: A total of 42,573 nerve fibres surrounding 100 coronary arteries (LMCA: n=21, LAD: n=27, LCx: n=26, RCA: n=26) were analysed. The nerve fibre diameter decreased along the vessel course (median [interquartile range]): (proximal 46 μm [31-73], middle 38 μm [26-58], distal 31 μm [22-46]; p<0.001), with the largest nerve fibre diameter along the LMCA (50 μm [31-81]), followed by the LAD (42 μm [27-72]; p<0.001). The total nerve fibre density was highest along the RCA (123 nerves/cm² [82-194]). Circumferentially, nerve density was higher in the myocardial tissue area of the coronary arteries (132 nerves/cm² [76-225]) than in the epicardial tissue area (101 nerves/cm² [61-173]; p<0.001). The median lumen-nerve distance was smallest around the LMCA (2.2 mm [1.2-4.1]), followed by the LAD (2.5 mm [1.1-4.5]; p=0.005)., Conclusions: Human coronary arteries are highly innervated with sympathetic nerve fibres, with significant variation in the distribution and density. Understanding these patterns informs pathophysiological understanding and, potentially, the development of catheter-based approaches for cardiac autonomic modulation.

This Perspective article is a form of 'pastiche', inspired by the 1993 review by Lincoff and Topol entitled 'Illusion of reperfusion', and explores how their concept continues to apply to percutaneous revascularization in patients with coronary artery disease and ischaemia. Just as Lincoff and Topol argued that reperfusion of acute myocardial infarction was facing unresolved obstacles that hampered clinical success in 1993, we propose that challenging issues are similarly jeopardizing the potential benefits of stent-based angioplasty today. By analysing the appropriateness and efficacy of percutaneous coronary intervention (PCI), we emphasize the limitations of relying solely on visual angiographic guidance, which frequently leads to inappropriate stenting and overtreatment in up to one-third of patients and the associated increased risk of periprocedural myocardial infarction. The lack of optimal revascularization observed in half of patients undergoing PCI confers risks such as suboptimal physiology after PCI, residual angina and long-term stent-related events, leaving an estimated 76% of patients with an 'illusion of revascularization'. These outcomes highlight the need to refine our diagnostic tools by integrating physiological assessments with targeted intracoronary imaging and emerging strategies, such as co-registration systems and angiography-based computational methods enhanced by artificial intelligence, to achieve optimal revascularization outcomes., (© 2024. Springer Nature Limited.)

Background and Aims: Guidelines suggest similar blood pressure (BP) targets in patients with and without diabetes and recommend ambulatory BP monitoring (ABPM) to diagnose and classify hypertension. It was explored whether different levels of ambulatory and office BP and different hypertension phenotypes associate with differences of risk in diabetes and no diabetes., Methods: This analysis assessed outcome data from the Spanish ABPM Registry in 59 124 patients with complete available data. The associations between office, mean, daytime, and nighttime ambulatory BP with the risk in patients with or without diabetes were explored. The effects of diabetes on mortality in different hypertension phenotypes, i.e. sustained hypertension, white-coat hypertension, and masked hypertension, compared with normotension were studied. Analyses were done with Cox regression analyses and adjusted for demographic and clinical confounders., Results: A total of 59 124 patients were recruited from 223 primary care centres in Spain. The majority had an office systolic BP >140 mmHg (36 700 patients), and 23 128 (40.6%) patients were untreated. Diabetes was diagnosed in 11 391 patients (19.2%). Concomitant cardiovascular (CV) disease was present in 2521 patients (23.1%) with diabetes and 4616 (10.0%) without diabetes. Twenty-four-hour mean, daytime, and nighttime ambulatory BP were associated with increased risk in diabetes and no diabetes, while in office BP, there was no clear association with no differences with and without diabetes. While the relative association of BP to CV death risk was similar in diabetes compared with no diabetes (mean interaction P = .80, daytime interaction P = .97, and nighttime interaction P = .32), increased event rates occurred in diabetes for all ABPM parameters for CV death and all-cause death. White-coat hypertension was not associated with risk for CV death (hazard ratio 0.86; 95% confidence interval 0.72-1.03) and slightly reduced risk for all-cause death in no diabetes (hazard ratio 0.89; confidence interval 0.81-0.98) but without significant interaction between diabetes and no diabetes. Sustained hypertension and masked hypertension in diabetes and no diabetes were associated with even higher risk. There were no significant interactions in hypertensive phenotypes between diabetes and no diabetes and CV death risk (interaction P = .26), while some interaction was present for all-cause death (interaction P = .043) and non-CV death (interaction P = .053)., Conclusions: Diabetes increased the risk for all-cause death, CV, and non-CV death at every level of office and ambulatory BP. Masked and sustained hypertension confer to the highest risk, while white-coat hypertension appears grossly neutral without interaction of relative risk between diabetes and no diabetes. These results support recommendations of international guidelines for strict BP control and using ABPM for classification and assessment of risk and control of hypertension, particularly in patients with diabetes., Clinical Trial Registration: Not applicable., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Patients with atrial fibrillation (AF) are at increased risk for thromboembolic events including stroke. The primary source for thromboembolism in these patients is thrombus formation in the left atrial appendage (LAA). Depending on the individual thromboembolic risk, long-term anticoagulation is recommended. In certain patients, however, long-term anticoagulation is contraindicated, and interventional closure of the LAA (LAAC) represents an alternative approach to lower the thromboembolic risk and avoid oral anticoagulation., Case Summary: An 83-year-old male underwent LAAC at our centre in November 2022. Prior to the procedure, a thrombus in the left atrium (LA) or LAA was excluded by transoesophageal echocardiography (TOE), and the anatomy of the LAA was assessed as eligible for LAAC with no evidence of anatomical irregularities. After contrast medium injection, angiography revealed an atypical anatomic variant of the LAA with a substantially long, elephant trunk-like course., Discussion: We present a previously not described unique anatomic variant of the LAA: the elephant trunk morphology. Left atrial appendage anatomy is very heterogeneous, and detailed knowledge of LAA morphology is important for endovascular LAA procedures as well as for predicting the risk of thromboembolic events. Despite thorough pre-procedural imaging, anatomic variants may remain obscured., Competing Interests: Conflict of interest: P.F. has received speaker honoraria from Astra Zeneca and Pfizer. F.M. is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219, Project-ID 322900939), and Deutsche Herzstiftung. Saarland University has received scientific support from Ablative Solutions, Medtronic and ReCor Medical. Until May 2024, F.M. has received speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. M.B. reports personal fees from Abbott, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, Servier, and Vifor. C.U. has received speaker horonaria/consulting fees from Aurigen, Bayer, Biosense Webster, Bristol Myers Squibb, Medtronic, Pfizer, and Recor Medical., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Visit-to-visit blood pressure (BP) variability associates with an increased risk of cardiovascular events. We investigated the role of seasonal BP modifications on the magnitude of BP variability and its impact on cardiovascular risk., Methods: In 25 390 patients included in the ONTARGET and TRANSCEND trials, the on-treatment systolic (S) BP values obtained by five visits during the first two years of the trials were grouped according to the month in which they were obtained. SBP differences between winter and summer months were calculated for BP variability quintiles (Qs), as quantified by the coefficient of variation (CV) of on-treatment mean SBP from the five visits. The relationship of BP variability with the risk of cardiovascular events and mortality was assessed by the Cox regression model., Results: SBP was approximately 4 mmHg lower in summer than in winter regardless of confounders. Winter/summer SBP differences contributed significantly to each SBP-CV quintile. Increase of SBP-CV from Q1 to Q5 was associated with a progressive increase in the adjusted hazard ratio (HR) of the primary endpoint of the trials, i.e. morbid and fatal cardiovascular events. This association was even stronger after removal of the effect of seasonality from the calculation of SBP-CV. A similar trend was observed for secondary endpoints., Conclusions: Winter/summer SBP differences significantly contribute to visit-to-visit BP variability. However, this contribution does not participate in the adverse prognostic significance of visit-to-visit BP variations, which seems to be more evident after removal of the BP effects of seasonality from visit-to-visit BP variations., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes., Aim: To perform a comprehensive meta-analysis of all randomized, sham-controlled trials investigating RDN with first- and second-generation devices in hypertension., Methods: We searched MEDLINE and Cochrane Library for eligible trials. Outcomes included both efficacy (24-hour and office systolic [SBP] and diastolic blood pressure [DBP]) and safety (all-cause death, vascular complication, renal artery stenosis >70%, hypertensive crisis) of RDN. We performed a study-level, pairwise, random-effects meta-analysis of the summary data., Results: Ten trials comprising 2,478 patients with hypertension while being either off- or on-treatment were included. Compared with sham, RDN reduced 24-hour and office systolic BP by 4.4 mmHg (95%CI -6.1, -2.7, p<0.00001) and 6.6 mmHg (95%CI -9.7, -3.6, p<0.0001), respectively. The 24-hour and office diastolic BP paralleled these findings (-2.6 mmHg, 95%CI - 3.6, -1.5, p<0.00001; -3.5 mmHg, 95%CI -5.4, -1.6, p=0.0003). There was no difference in 24-hour and office SBP reduction between trials with and without concomitant antihypertensive medication (p for interaction 0.62 and 0.73, respectively). There was no relevant difference concerning vascular complications (OR 1.69, 95%CI 0.57-5.0, p=0.34), renal artery stenosis (OR 1.50, 95%CI 0.06-36.97, p=0.80), hypertensive crisis (OR 0.65, 95%CI 0.30-1.38, p=0.26) and all-cause death (OR 1.76, 95%CI 0.34-9.20, p=0.50) between RDN and sham groups. Change of renal function based on eGFR was comparable between groups (p for interaction 0.84). There was significant heterogeneity between trials., Conclusions: RDN safely reduces ambulatory and office SBP/DBP vs. a sham procedure in the presence and absence of antihypertensive medication., Clinical Perspective: What is new?Several sham-controlled trials have investigated the efficacy and safety of catheter-based renal denervation (RDN) with mixed outcomes.This comprehensive meta-analysis comprising 2,478 patients shows that irrespective of the utilized method (radiofrequency-, ultrasound-or alcohol-mediated), renal denervation effectively reduced ambulatory and office systolic blood pressure.Renal denervation exhibited no additional risk concerning vascular injury or renal function impairment.What are the clinical implications?This meta-analysis supports current guidelines/consensus statements that renal denervation represents an additive treatment option in carefully selected patients with uncontrolled hypertension.

Background: Renal denervation (RDN) has demonstrated clinically relevant reductions in blood pressure (BP) among individuals with uncontrolled hypertension despite lifestyle intervention and medications. The safety and effectiveness of alcohol-mediated RDN have not been formally studied in this indication., Methods: TARGET BP I is a prospective, international, sham-controlled, randomized, patient- and assessor-blinded trial investigating the safety and efficacy of alcohol-mediated RDN. Patients with office systolic BP (SBP) ≥150 and ≤180 mm Hg, office diastolic BP ≥90 mm Hg, and mean 24-hour ambulatory SBP ≥135 and ≤170 mm Hg despite prescription of 2 to 5 antihypertensive medications were enrolled. The primary end point was the baseline-adjusted change in mean 24-hour ambulatory SBP 3 months after the procedure. Secondary end points included mean between-group differences in office and ambulatory BP at additional time points., Results: Among 301 patients randomized 1:1 to RDN or sham control, RDN was associated with a significant reduction in 24-hour ambulatory SBP at 3 months (mean±SD, -10.0±14.2 mm Hg versus -6.8±12.1 mm Hg; treatment difference, -3.2 mm Hg [95% CI, -6.3 to 0.0]; P =0.0487). Subgroup analysis of the primary end point revealed no significant interaction across predefined subgroups. At 3 months, the mean change in office SBP was -12.7±18.3 and -9.7±17.3 mm Hg (difference, -3.0 [95% CI, -7.0 to 1.0]; P =0.173) for RDN and sham, respectively. No significant differences in ambulatory or office diastolic BP were observed. Adverse safety events through 6 months were uncommon, with one instance of accessory renal artery dissection in the RDN group (0.7%). No significant between-group differences in medication changes or patient adherence were identified., Conclusions: Alcohol-mediated RDN was associated with a modest but statistically significant reduction in 24-hour ambulatory SBP compared with sham control. No significant differences between groups in office BP or 6-month major adverse events were observed., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02910414., Competing Interests: Disclosures Dr Kandzari received institutional research/grant support and support for attending meetings from Medtronic and Ablative Solutions Inc, personal consulting honoraria from Medtronic and HyperQure, and has equity in BioStar (none related to Ablative Solutions Inc). Dr Wever received consulting fees from Medtronic, ReCor, Ablative Solutions Inc, Johnson & Johnson, and Urovant. Dr Pathak received consulting fees from Medtronic, Merck, Servier, and Ablative Solutions and speaker honoraria/support for attending meetings from Ablative Solutions, Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, Merck, Novartis, Omron, ReCor Medical, Recordati, and Servier. He is a board member of the European Society of Hypertension, is a past president of the French Society of Cardiology, and is president-elect of the French Foundation for Research in Hypertension. Dr Zidar received study fees to the institution for enrolled patients from North Carolina Heart & Vascular research and consulting fees from Cordis Corp. M. Saxena received institutional grants from Ablative Solutions, ReCor Medical, Applied Therapeutics, and MSD, as well as consulting fees from Novartis, AstraZeneca, Mineralys, BI, ReCor Medical, Esperion, and Vifor Pharma. Dr David is a consultant for the Medtronic structural heart program. Dr Schmieder received grants, consulting fees, and honoraria from Ablative Solutions, Medtronic, and ReCor Medical. Dr Langer is an unpaid speaker of the Radial Working Group of the German Society of Cardiology. Dr Persu received grants from Servier and ReCor Medical, speaker honoraria from Servier, ReCor, Medical, and Sanofi, has participated on advisory boards for ReCor Medical, and received equipment and medical writing support from Ablative Solutions Inc. Dr Fischell possesses the license of patents and potential royalties with stock options in Ablative Solutions Inc and is the chief medical officer of Ablative Solutions Inc. Dr Persu receives institutional/grant support, personal consulting fees, and support for attending meetings/travel from Ablative Solutions, Inc. Dr Mendelsohn is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219), and Deutsche Herzstiftung. His institution (Saarland University) has received scientific support from Ablative Solutions, Medtronic, and ReCor Medical. He received speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. The other authors report no conflicts.

Background and Aims: There is significant potential to streamline the clinical pathway for patients undergoing transcatheter aortic valve implantation (TAVI). The purpose of this study was to evaluate the effect of implementing BENCHMARK best practices on the efficiency and safety of TAVI in 28 sites in 7 European countries., Methods: This was a study of patients with severe symptomatic aortic stenosis (AS) undergoing TAVI with balloon-expandable valves before and after implementation of BENCHMARK best practices. Principal objectives were to reduce hospital length of stay (LoS) and duration of intensive care stay. Secondary objective was to document patient safety., Results: Between January 2020 and March 2023, 897 patients were documented prior to and 1491 patients after the implementation of BENCHMARK practices. Patient characteristics were consistent with a known older TAVI population and only minor differences. Mean LoS was reduced from 7.7 ± 7.0 to 5.8 ± 5.6 days (median 6 vs. 4 days; P < .001). Duration of intensive care was reduced from 1.8 to 1.3 days (median 1.1 vs. 0.9 days; P < .001). Adoption of peri-procedure best practices led to increased use of local anaesthesia (96.1% vs. 84.3%; P < .001) and decreased procedure (median 47 vs. 60 min; P < .001) and intervention times (85 vs. 95 min; P < .001). Thirty-day patient safety did not appear to be compromised with no differences in all-cause mortality (0.6% in both groups combined), stroke/transient ischaemic attack (1.4%), life-threatening bleeding (1.3%), stage 2/3 acute kidney injury (0.7%), and valve-related readmission (1.2%)., Conclusions: Broad implementation of BENCHMARK practices contributes to improving efficiency of TAVI pathway reducing LoS and costs without compromising patient safety., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Catheter-based renal denervation (RDN) reduces blood pressure in hypertension. Urinary peptides are associated with cardiovascular and renal disease and provide prognostic information. We aimed to investigate the effect of RDN on urinary peptide-based classifiers associated with chronic kidney and heart disease and to identify urinary peptides affected by RDN., Methods: This single-arm, single-center study included patients undergoing catheter-based RDN. Urine samples were collected before and 24 months after RDN and were analyzed using capillary electrophoresis coupled with mass spectrometry. Predefined urinary peptide-based classifiers for chronic kidney disease (CKD273), coronary artery disease (CAD238), and heart failure (HF1) were applied., Results: This study included 48 patients (33% female) with uncontrolled hypertension. At 24 months after RDN, systolic blood pressure (165±17 versus 148±20 mm Hg; P <0.0001), diastolic blood pressure (90±17 versus 81±13 mm Hg; P <0.0001), and mean arterial pressure (115±15 versus 103±13 mm Hg; P <0.0001) decreased significantly. A total of 103 urinary peptides from 37 different proteins, mostly collagens, altered following RDN. CAD238, a 238 coronary artery-specific polypeptide-based classifier, significantly improved following RDN (Cohen's d , -0.632; P =0.0001). The classification scores of HF1 ( P =0.8295) and CKD273 ( P =0.6293) did not change significantly., Conclusions: RDN beneficially affected urinary peptides associated with coronary artery disease., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01888315., Competing Interests: Disclosures L. Lauder reports speaker honoraria from AstraZeneca, Medtronic, Pfizer, and ReCor Medical. J. Siwy and E. Mavrogeorgis are employees of the Mosaiques Diagnostics GmbH. I.E. Emrich has received speaker honoraria/consulting fees from Pharmacosmos, Astellas, Bristol Myers Squibb, AstraZeneca, and Novartis. M. Böhm is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project No. 322900939) and reports personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Edwards, Medtronic, Novartis, ReCor Medical, Servier, and Vifor during the conduct of the study. H. Mischak is cofounder and a shareholder of Mosaiques Diagnostics GmbH. F. Mahfoud is supported by Deutsche Gesellschaft für Kardiologie, Deutsche Forschungsgemeinschaft (SFB TRR219, project ID 322900939), and Deutsche Herzstiftung. His institution (Saarland University) has received scientific support from Ablative Solutions, Medtronic, and ReCor Medical, and speaker honoraria/consulting fees from Ablative Solutions, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. The other authors report no conflicts.

Background: Endothelial activation promotes the release of procoagulant extracellular vesicles and inflammatory mediators from specialized storage granules. Endothelial membrane exocytosis is controlled by phosphorylation. We hypothesized that the absence of PTP1B (protein tyrosine phosphatase 1B) in endothelial cells promotes venous thromboinflammation by triggering endothelial membrane fusion and exocytosis., Methods: Mice with inducible endothelial deletion of PTP1B (End.PTP1B-KO) underwent inferior vena cava ligation to induce stenosis and venous thrombosis. Primary endothelial cells from transgenic mice and human umbilical vein endothelial cells were used for mechanistic studies., Results: Vascular ultrasound and histology showed significantly larger venous thrombi containing higher numbers of Ly6G (lymphocyte antigen 6 family member G)-positive neutrophils in mice with endothelial PTP1B deletion, and intravital microscopy confirmed the more pronounced neutrophil recruitment following inferior vena cava ligation. RT 2 PCR profiler array and immunocytochemistry analysis revealed increased endothelial activation and adhesion molecule expression in primary End.PTP1B-KO endothelial cells, including CD62P (P-selectin) and VWF (von Willebrand factor). Pretreatment with the NF-κB (nuclear factor kappa B) kinase inhibitor BAY11-7082, antibodies neutralizing CD162 (P-selectin glycoprotein ligand-1) or VWF, or arginylglycylaspartic acid integrin-blocking peptides abolished the neutrophil adhesion to End.PTP1B-KO endothelial cells in vitro. Circulating levels of annexin V + procoagulant endothelial CD62E + (E-selectin) and neutrophil (Ly6G + ) extracellular vesicles were also elevated in End.PTP1B-KO mice after inferior vena cava ligation. Higher plasma MPO (myeloperoxidase) and Cit-H3 (citrullinated histone-3) levels and neutrophil elastase activity indicated neutrophil activation and extracellular trap formation. Infusion of End.PTP1B-KO extracellular vesicles into C57BL/6J wild-type mice most prominently enhanced the recruitment of endogenous neutrophils, and this response was blunted in VWF-deficient mice or by VWF-blocking antibodies. Reduced PTP1B binding and tyrosine dephosphorylation of SNAP23 (synaptosome-associated protein 23) resulting in increased VWF exocytosis and neutrophil adhesion were identified as mechanisms, all of which could be restored by NF-κB kinase inhibition using BAY11-7082., Conclusions: Our findings show that endothelial PTP1B deletion promotes venous thromboinflammation by enhancing SNAP23 phosphorylation, endothelial VWF exocytosis, and neutrophil recruitment., Competing Interests: Disclosures None.

Background: Anticoagulation (AC) is the guideline-recommended treatment for intermediate-risk pulmonary embolism (PE); however, it remains unclear whether mechanical thrombectomy provides benefit over AC alone. The PEERLESS II study aims to evaluate outcomes in intermediate-risk PE patients randomized to treatment with large-bore mechanical thrombectomy and AC vs AC alone., Methods: PEERLESS II is an international randomized controlled trial enrolling up to 1200 patients with intermediate-risk PE and additional clinical risk factors from up to 100 sites. Treatment is randomized 1:1 to large-bore mechanical thrombectomy with the FlowTriever System (Inari Medical) and AC or AC alone. Outcomes will be evaluated for up to 3 months, with safety events independently adjudicated. The primary end point is a hierarchical composite win ratio of (1) all-cause mortality by 30 days, (2) clinical deterioration (earlier of discharge or 30 days), (3) all-cause hospital readmission by 30 days, (4) bailout therapy (earlier of discharge or 30 days), and (5) Modified Medical Research Council (mMRC) dyspnea score of ≥1 at the 48-hour visit. Secondary end points include all-cause and PE-related mortality (30-day and 90-day), all-cause and PE-related readmission (30-day and 90-day), major bleeding (30-day and 90-day), clinical deterioration (earlier of discharge or 30 days), bailout (earlier of discharge or 30 days), right ventricle-to-left ventricle diameter ratio (48-hour visit), mMRC dyspnea score (48-hour, 1-month, and 3-month visits), quality of life using Pulmonary Embolism Quality of Life and EuroQol-5 Dimensions-5 Levels (1-month and 3-month visits), 6-minute walk distance (1-month visit), and post-PE impairment diagnosis (3-month visit)., Conclusions: PEERLESS II will inform the understanding of mechanical thrombectomy treatment for intermediate-risk PE and provide evidence for consideration in future treatment guidelines., Competing Interests: Jay Giri reports consulting fees, speaking fees, and research funds to the institution from Inari Medical and Boston Scientific and equity in Endovascular Engineering. Felix Mahfoud is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219, Project-ID 322900939), and Deutsche Herzstiftung. His institution (Saarland University) has received scientific support from Ablative Solutions, Medtronic, and ReCor Medical. He has received speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari Medical, Medtronic, Merck, ReCor Medical, Servier, and Terumo. Bernhard Gebauer reports consulting fees, speaking fees, and research funds to the institution from Inari Medical, BAYER, CALYX, Boston Scientific, ICON, Terumo, SIRTex Medical, and Siemens Healthineers. Asger Andersen reports speaking fees from Abbott, Gore Medical, Angiodynamics, EPS Vascular, and Jannsen and consulting fees from Inari Medical and Magneto thrombectomy solutions. Oren Friedman reports consulting fees from Inari Medical. Ripal Gandhi reports consulting fees and speaking fees from Boston Scientific, Inari Medical, Medtronic, Argon Medical, and Penumbra. Wissam Jaber reports consulting fees from Inari Medical, Medtronic, RapidAI, Abbott, and equity in Thrombolex. Keith Pereira reports having no conflicts relevant to this work. Frances West reports consulting and speaking fees from Inari Medical and Penumbra and serves on the board of directors for the PERT Consortium., (© 2024 The Author(s).)

Background: The SPYRAL HTN-ON MED (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications)trial showed significant office and nighttime systolic blood pressure (BP) reductions in patients with hypertension following renal denervation (RDN) compared with sham-control patients, despite similar 24-hour BP reductions. We compared antihypertensive medication and BP changes among prespecified subpopulations., Methods: The multicenter, randomized, sham-controlled, blinded SPYRAL HTN-ON MED trial (n=337) evaluated BP changes after RDN compared with a sham procedure in patients with hypertension prescribed 1 to 3 antihypertensive drugs. Most patients (n=187; 54%) were enrolled outside the United States, while 156 (46%) US patients were enrolled, including 60 (18%) Black Americans., Results: Changes in detected antihypertensive drugs were similar between RDN and sham group patients in the outside US cohort, while drug increases were significantly more common in the US sham group compared with the RDN group. Patients from outside the United States showed significant reductions in office and 24-hour mean systolic BP at 6 months compared with the sham group, whereas BP changes were similar between RDN and sham in the US cohort. Within the US patient cohort, Black Americans in the sham control group had significant increases in medication burden from baseline through 6 months ( P =0.003) but not in the RDN group ( P =0.44)., Conclusions: Patients enrolled outside the United States had minimal antihypertensive medication changes between treatment groups and had significant office and 24-hour BP reductions compared with the sham group. Increased antihypertensive drug burden in the US sham cohort, especially among Black Americans, may have diluted the treatment effect in the combined trial population., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02439775., Competing Interests: Disclosures R.R. Townsend is a consultant for Medtronic, Cytel, Novartis, Regeneron, and Janssen. He also receives royalties from UpToDate. K.C. Ferdinand is a consultant for Medtronic, Novartis, and Janssen. D.E. Kandzari reports institutional research/grant support from Biotronik, Boston Scientific, Cardiovascular Systems, Inc, Orbus Neich, Teleflex, Medtronic, and Ablative Solutions and personal consulting honoraria from Cardiovascular Systems, Inc, Medtronic, and Abbott Vascular. K. Kario receives personal fees from Medtronic during the conduct of the study; grants from A&D, Omron Healthcare, Fukuda Denshi, CureApp, Sanwa Kagaku Kenkyusho, Teijin Pharma, Boehringer Ingelheim Japan, and Fukuda Lifetec; consulting fees from A&D, JIMRO, Omron Healthcare, CureApp, Terumo, and Fukuda Denshi; honoraria from Otsuka Pharmaceuticals and Omron Healthcare; and participation in Advisory Board of Fukuda Denshi, outside the submitted work. F. Mahfoud is supported by Deutsche Gesellschaft für Kardiologie, Deutsche Forschungsgemeinschaft (SFB TRR219), and Deutsche Herzstiftung. He has received scientific support from Ablative Solutions, Medtronic, and ReCor Medical and speaker honoraria/consulting fees from Ablative Solutions, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. M.A. Weber has received consulting fees from Medtronic, ReCor Medical, Ablative Solutions, Johnson & Johnson, and Urovant. R.E. Schmieder reports grants and personal fees from Medtronic, ReCor Medical, and Ablative Solutions. S. Pocock reports personal fees from Medtronic outside the submitted work. K. Tsioufis reports institutional research/grant support from Medtronic and ReCor Medical and personal consulting honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, ReCor Medical, Servier, WinMedica, and ELPEN. A. Walton is a proctor, on the medical advisory board, and has received grant support from Medtronic, Edwards, and Abbott. I. Hopper has received honoraria from Boehringer Ingelheim, Eli Lilly, AstraZeneca, and Vifor. B. Bertolet serves on the Medtronic Renal Denervation Advisory Committee as a consultant. F. Sharif is supported by Science Foundation Ireland Research Infrastructure (17/RI/5353) and is a consultant and advisory board member for Medtronic. K. Fengler received institutional grants from Medtronic, ReCor Medical, and Biotronic. M. Fahy, D.A. Hettrick, and S. Brar are employees of Medtronic. M. Böhm is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322900939) and reports personal fees from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, ReCor Medical, Servier, and Vifor during the conduct of the study. The other authors report no conflicts.

Background: Quantification of total cardiovascular risk is essential for individualizing hypertension treatment. This study aimed to develop and validate a novel, machine-learning-derived model to predict cardiovascular mortality risk using office blood pressure (OBP) and ambulatory blood pressure (ABP)., Methods: The performance of the novel risk score was compared with existing risk scores, and the possibility of predicting ABP phenotypes utilizing clinical variables was assessed. Using data from 59 124 patients enrolled in the Spanish ABP Monitoring registry, machine-learning approaches (logistic regression, gradient-boosted decision trees, and deep neural networks) and stepwise forward feature selection were used., Results: For the prediction of cardiovascular mortality, deep neural networks yielded the highest clinical performance. The novel mortality prediction models using OBP and ABP outperformed other risk scores. The area under the curve achieved by the novel approach, already when using OBP variables, was significantly higher when compared with the area under the curve of the Framingham risk score, Systemic Coronary Risk Estimation 2, and Atherosclerotic Cardiovascular Disease score. However, the prediction of cardiovascular mortality with ABP instead of OBP data significantly increased the area under the curve (0.870 versus 0.865; P =3.61×10 - 28 ), accuracy, and specificity, respectively. The prediction of ABP phenotypes (ie, white-coat, ambulatory, and masked hypertension) using clinical characteristics was limited., Conclusions: The receiver operating characteristic curves for cardiovascular mortality using ABP and OBP with deep neural network models outperformed all other risk metrics, indicating the potential for improving current risk scores by applying state-of-the-art machine learning approaches. The prediction of cardiovascular mortality using ABP data led to a significant increase in area under the curve and performance metrics.

Arterial hypertension is a global leading cause of cardiovascular, cerebrovascular, and renal disease, as well as mortality. Although pharmacotherapy is safe and effective in lowering blood pressure (BP) and cardiovascular disease risk, BP control remains poor, and the mortality rates associated with high BP have been steadily increasing. Device-based therapies have been investigated to overcome barriers to pharmacotherapy, including non-adherence and low rates of persistence to daily medications. Among these device-based therapies, catheter-based renal denervation (RDN) has been most extensively examined over the past 15 years. In this state-of-the-art article, we summarise the rationale for RDN, review the available evidence, provide recommendations for a safe procedure, and discuss the role of RDN in current guidelines and clinical practice.

Background: Ultrasound-assisted thrombolysis (USAT) and large-bore-thrombectomy (LBT) are under investigation for the treatment of intermediate-high and high-risk pulmonary embolisms (PE). Comparative studies investigating both devices are scarce., Aims: This study aimed to compare the safety and efficacy of the two most frequently used devices for treatment of acute PE., Methods: This multicenter, retrospective study included 125 patients undergoing LBT or USAT for intermediate- or high-risk PE between 2019 and 2023. Nearest neighbor propensity matching with logistic regression was used to achieve balance on potential confounders. The primary outcome was the change in the right to left ventricular (RV/LV) ratio between baseline and 24 h., Results: A total of 125 patients were included. After propensity score matching, 95 patients remained in the sample, of which 69 (73%) underwent USAT and 26 (27%) LBT. The RV/LV ratio decrease between baseline and 24 h was greater in the LBT than in the USAT group (adjusted between-group difference: -0.10, 95% CI: -0.16 to -0.04; p = 0.001). Both procedures were safe and adverse events occurred rarely (10% following USAT vs. 4% following LBT; p = 0.439)., Conclusion: In acute intermediate-high and high-risk PE, both LBT and USAT were feasible and safe. The reduction in RV/LV ratio was greater following LBT than USAT. Further randomized controlled trials are needed to confirm these findings., (© 2024 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: The randomized, sham-controlled RADIANCE-HTN (A Study of the Recor Medical Paradise System in Clinical Hypertension) SOLO, RADIANCE-HTN TRIO, and RADIANCE II (A Study of the Recor Medical Paradise System in Stage II Hypertension) trials independently met their primary end point of a greater reduction in daytime ambulatory systolic blood pressure (SBP) 2 months after ultrasound renal denervation (uRDN) in patients with hypertension. To characterize the longer-term effectiveness and safety of uRDN versus sham at 6 months, after the blinded addition of antihypertensive treatments (AHTs), we pooled individual patient data across these 3 similarly designed trials., Methods: Patients with mild to moderate hypertension who were not on AHT or with hypertension resistant to a standardized combination triple AHT were randomized to uRDN (n=293) versus sham (n=213); they were to remain off of added AHT throughout 2 months of follow-up unless specified blood pressure (BP) criteria were exceeded. In each trial, if monthly home BP was ≥135/85 mm Hg from 2 to 5 months, standardized AHT was sequentially added to target home BP <135/85 mm Hg under blinding to initial treatment assignment. Six-month outcomes included baseline- and AHT-adjusted change in daytime ambulatory, home, and office SBP; change in AHT; and safety. Linear mixed regression models using all BP measurements and change in AHT from baseline through 6 months were used., Results: Patients (70% men) were 54.1±9.3 years of age with a baseline daytime ambulatory/home/office SBP of 150.5±9.8/151.0±12.4/155.5±14.4 mm Hg, respectively. From 2 to 6 months, BP decreased in both groups with AHT titration, but fewer uRDN patients were prescribed AHT ( P =0.004), and fewer additional AHT were prescribed to uRDN patients versus sham patients ( P =0.001). Whereas the unadjusted between-group difference in daytime ambulatory SBP was similar at 6 months, the baseline and medication-adjusted between-group difference at 6 months was -3.0 mm Hg (95% CI, -5.7, -0.2; P =0.033), in favor of uRDN+AHT. For home and office SBP, the adjusted between-group differences in favor of uRDN+AHT over 6 months were -5.4 mm Hg (-6.8, -4.0; P <0.001) and -5.2 mm Hg (-7.1, -3.3; P <0.001), respectively. There was no heterogeneity between trials. Safety outcomes were few and did not differ between groups., Conclusions: This individual patient-data analysis of 506 patients included in the RADIANCE trials demonstrates the maintenance of BP-lowering efficacy of uRDN versus sham at 6 months, with fewer added AHTs., Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02649426 and NCT03614260., Competing Interests: Disclosures Dr Azizi reports receiving grants from the European Horizon 2020 program; grants and nonfinancial support from Recor Medical, Idorsia, and Novartis; and personal fees from Alnylam Pharmaceuticals, Cincor, Medtronic, AstraZeneca, and Novartis. Dr Sharp has received personal fees from Recor Medical, Medtronic, Boston Scientific, Penumbra, and Philips. Dr Fisher has received grant support and personal fees from Recor Medical and personal fees from Medtronic. Dr Lobo has received personal fees from Recor Medical, Medtronic, Ablative Solutions, and Vascular Dynamics; and has received grants from Medtronic. Dr Daemen received institutional grant or research support from Abbott Vascular, Boston Scientific, ACIST Medical, Medtronic, Microport, Pie Medical, and Recor Medical, and consultancy or speaker fees from Abbott Vascular, Abiomed, ACIST Medical, Boston Scientific, Cardialysis BV, CardiacBooster, Kaminari Medical, Recor Medical, PulseCath, Pie Medical, Sanofi, Siemens Health Care, and Medtronic. Dr Lurz has received institutional grant support from Recor Medical, Edwards Lifesciences, and Abbott. Dr Mahfoud is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219, project ID 322900939), and Deutsche Herzstiftung; and has received scientific support from Ablative Solutions, Medtronic, and Recor Medical, and speaker honoraria or consulting fees from Ablative Solutions, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, Recor Medical, Servier, and Terumo. Dr Schmieder has received grant support and personal fees from Recor Medical, Medtronic, and Ablative Solutions. Dr Basile has received grant support from Recor Medical and Ablative Solutions. Dr Bloch has received personal fees from Recor Medical and Medtronic. Dr Weber has received personal fees from Recor Medical, Medtronic, and Ablative Solutions. Dr Saxena has received grant support from Recor Medical, Ablative Solutions, Applied Therapeutics, Vascular Dynamics, and MSD; and has received consulting fees from Recor Medical, Esperion Inc., Daiichi Sankyo Inc., Novartis, and Vifor Pharma. Dr Wang reports no relationships relevant to the contents of this article to disclose. Dr Sanghvi has received grant support and personal fees from Recor Medical and Medtronic and has received grant support from CSI. Dr Jenkins reports institutional funding to Ochsner Medical Center from Medtronic, Abbott, Abiomed, and Recor Medical; and in addition to research grants, he has received honoraria for speaking engagements or proctoring consulting from Abbott, Recor Medical, and Medtronic. Dr Devireddy has received personal fees from Recor Medical, Medtronic, Edwards Lifesciences, and Shockwave Medical. Dr Rader has received personal fees from Recor Medical, Medtronic, and Bristol Myers Squibb. Dr Gosse has received research grant support from Recor Medical. L. Claude and Dr Dimitri Augustin are employees of Recor Medical. Dr McClure is an employee of NAMSA, a contractor for Recor Medical. Dr Kirtane reports institutional funding to Columbia University or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, and Recor Medical; in addition to research grants, institutional funding includes fees paid to Columbia University or Cardiovascular Research Foundation for speaking engagements or consulting; personal fees for consulting from Neurotronic; and travel expenses or meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, Recor Medical, Chiesi, OpSens, Zoll, and Regeneron.

Aims: The triglyceride-glucose index (TyG) has been proposed as an alternative to insulin resistance and as a predictor of cardiovascular outcomes. Little is known on its role in chronic stable cardiovascular disease and its predictive power at controlled low density lipoprotein (LDL) levels., Methods and Results: Our study population consisted of 29 960 participants in the ONTARGET and TRANSCEND trials that enrolled patients with known atherosclerotic disease. Triglycerides and glucose were measured at baseline. TyG was calculated as the logarithmized product of fasting triglycerides and glucose divided by 2. The primary endpoint of both trials was a composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure. The secondary endpoint was all-cause death and the components of the primary endpoint. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) with extensive covariate adjustment for demographic, medical history, and lifestyle factors. During a mean follow-up of 4.3 years, 4895 primary endpoints and 3571 all-cause deaths occurred. In fully adjusted models, individuals in the highest compared to the lowest quartile of the TyG index were at higher risk for the primary endpoint (HR 1.14; 95% CI 1.05-1.25) and for myocardial infarction (HR 1.30; 95% CI 1.11-1.53). A higher TyG index did not associate with the primary endpoint in individuals with LDL levels < 100 mg/dL., Conclusion: A higher TyG index is associated with a modestly increased cardiovascular risk in chronic stable cardiovascular disease. This association is largely attenuated when LDL levels are controlled., Registration: www.clinicaltrials.gov: NCT00153101., Competing Interests: Conflict of interest: M.B. is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322900939) and reports personal fees from Abbott, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Medtronic, Novartis, Servier, and Vifor during the conduct of the study. B.H. reports no conflicts. F.M. reports grants and personal fees from Medtronic and personal fees from Recor, Boehringer Ingelheim, and Berlin Chemie. He is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219, project number 322900939), and Deutsche Herzstiftung, has received scientific support and/or speaker honoraria from Ablative Solutions, Medtronic, and ReCor Medical, and speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. G.M. reports no conflicts. J.F.E.M. reports no conflicts. R.S. reports no conflicts. H.S. reports personal fees from Boehringer Ingelheim. K.K.T. reports no conflicts. E.M.L. reports no conflicts. S.Y. reports institutional grants for the ONTARGET and TRANSCEND trials but not related to the current analysis., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Despite remarkable improvements in the management of heart failure (HF), HF remains one of the most rapidly growing cardiovascular condition resulting in a substantial burden on healthcare systems worldwide. In clinical practice, however, a relevant proportion of patients are treated with suboptimal combinations and doses lower than those recommended in the current guidelines. Against this background, it remains important to identify new targets and investigate additional therapeutic options to alleviate symptoms and potentially improve prognosis in HF. Therefore, non-pharmacological interventions targeting autonomic imbalance in HF have been evaluated. This paper aims to review the physiology, available clinical data, and potential therapeutic role of device-based neuromodulation in HF., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Resistant hypertension (RH) is a severe form of hypertension associated with increased cardiovascular risk. Although true RH affects less than 10% of the patients receiving antihypertensive therapy, the absolute number is high and continues to increase. The workup of these patients requires screening for secondary hypertension and pseudoresistance, including poor adherence to prescribed medicines and the white-coat phenomenon. The treatment of RH consists of lifestyle modifications and pharmacological therapies. Lifestyle modifications include dietary adjustments, weight loss, physical activity, and limiting alcohol consumption; pharmacological therapies include diuretics, mineralocorticoid receptor antagonists, beta blockers, angiotensin receptor-neprilysin inhibitors, and others. Over the last 15 years, interventional approaches have emerged as adjunct treatment options; we highlight catheter-based renal denervation. This review summarizes the rationales and latest clinical evidence and, based thereon, proposes an updated algorithm for the management of RH.