Impact of Renal Denervation on Urinary Peptide-Based Biomarkers in Hypertension.

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.

Ultra-long-term efficacy and safety of catheter-based renal denervation in resistant hypertension: 10-year follow-up outcomes.

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/1.73m2 (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.

Comparison of three creatinine-based equations to predict adverse outcome in a cardiovascular high-risk cohort: an investigation using the SPRINT research materials.

Background: Novel creatinine-based equations have recently been proposed but their predictive performance for cardiovascular outcomes in participants at high cardiovascular risk in comparison to the established CKD-EPI 2009 equation is unknown. Method: In 9361 participants from the United States included in the randomized controlled SPRINT trial, we calculated baseline estimated glomerular filtration rate (eGFR) using the CKD-EPI 2009, CKD-EPI 2021, and EKFC equations and compared their predictive value of cardiovascular events. The statistical metric used is the net reclassification improvement (NRI) presented separately for those with and those without events. Results: During a mean follow-up of 3.1 ± 0.9 years, the primary endpoint occurred in 559 participants (6.0%). When using the CKD-EPI 2009, the CKD-EPI 2021, and the EKFC equations, the prevalence of CKD (eGFR <60 ml/min/1.73 m2 or >60 ml/min/1.73 m2 with an ACR ≥30 mg/g) was 37% vs. 35.3% (P = 0.02) vs. 46.4% (P < 0.001), respectively. The corresponding mean eGFR was 72.5 ± 20.1 ml/min/1.73 m2 vs. 73.2 ± 19.4 ml/min/1.73 m2 (P < 0.001) vs. 64.6 ± 17.4 ml/min/1.73 m2 (P < 0.001). Neither reclassification according to the CKD-EPI 2021 equation [CKD-EPI 2021 vs. CKD-EPI 2009: NRIevents: -9.5% (95% confidence interval (CI) -13.0% to -5.9%); NRInonevents: 4.8% (95% CI 3.9% to 5.7%)], nor reclassification according to the EKFC equation allowed better prediction of cardiovascular events compared to the CKD-EPI 2009 equation (EKFC vs. CKD-EPI 2009: NRIevents: 31.2% (95% CI 27.5% to 35.0%); NRInonevents: -31.1% (95% CI -32.1% to -30.1%)). Conclusion: Substituting the CKD-EPI 2009 with the CKD-EPI 2021 or the EKFC equation for calculation of eGFR in participants with high cardiovascular risk without diabetes changed the prevalence of CKD but was not associated with improved risk prediction of cardiovascular events for both those with and without the event.

Radio frequency-based renal denervation: a story of simplicity?

Radio frequency-based renal denervation is a safe and effective way of lowering blood pressure, a common condition associated with high cardiovascular risk. Several catheters have been developed to administer energy to the renal arteries and their side branches, thereby modulating sympathetic renal activity. The Symplicity Flex™ and Symplicity Spyral™ are first- and second-generation devices, respectively, for radio frequency-based renal denervation. There is a continuous need to further improve and adjust interventional antihypertensive therapies. Several randomized controlled trials have been conducted to investigate the safety and efficacy of these catheters and most were able to show radio frequency-based renal denervation to be feasible, safe and effective in lowering blood pressure in hypertensive patients with and without concomitant antihypertensive medication. Herein, the authors discuss the pathophysiologic concepts of renal denervation and its procedural approaches, report catheter designs, summarize clinical trials outcomes and, finally, discuss real-world evidence.

High blood pressure causes illness and death worldwide. Treatment of high blood pressure is usually based on lifestyle modification and blood pressure-lowering drugs. Renal denervation represents a minimally invasive approach to lower blood pressure by interrupting the nerves surrounding the renal arteries. These nerves are involved in the body's fight-or-flight and rest-and-digest systems, the so-called autonomous nervous system. The Spyral™ catheter system uses radio frequency energy to modulate renal nerve activity. Trials have consistently shown that renal denervation is safe. The first-generation catheter was a monoelectrode catheter called Symplicity Flex™ and several points in the renal artery had to be treated. The second-generation device called the Symplicity Spyral™ catheter, on the other hand, has a multielectrode design and consequently fewer ablation points are sufficient for complete denervation. Caused by the positive effects on blood pressure and the consistent safety reports, renal denervation is considered by current guidelines as an alternative and additive treatment approach in patients with high blood pressure.

A randomized, placebo-controlled, trial to assess the photosensitizing, phototoxic and carcinogenic potential of hydrochlorothiazide in healthy volunteers.

BACKGROUND AND AIMS: Pharmacovigilance reports, associating hydrochlorothiazide (HCT) with skin cancer, resulted in a significant decrease of HCT prescriptions for hypertension and heart failure. Whether HCT exhibits phototoxic properties thereby causing skin cancer remains unknown. This study aimed to examine the photosensitizing, phototoxic and carcinogenic potential of HCT in a randomized, placebo-controlled, double-blind trial in vivo and also in vitro . METHODS: The trial assigned 30 healthy, normotensive adult volunteers in a 2:1 ratio to either HCT 25 mg/day or placebo for 15 days. Photosensitivity of the skin with and without the effect of HCT treatment were assessed. Following whole-body ultraviolet A (UVA) and B (UVB, 311 nm) irradiation, phototoxic and carcinogenic reactions by measuring urinary excretion of pyrimidine dimers were evaluated. For the in-vitro studies, human keratinocytes (HaCaT) were incubated with HCT, irradiated with UVB, and analysed for markers of inflammation, apoptosis and carcinogenesis. RESULTS: Skin photosensitivity following exposure to UVA and UVB remained unchanged from baseline to 15-day follow-up in both groups (UVA change HCT 0.0 J/cm 2 vs. placebo 0.0 J/cm 2 ; P  = 0.99; UVB change HCT 0.0 J/cm 2 vs. placebo -0.2 J/cm 2 ; P  = 0.06). Pyrimidine dimers were not detected in either group. In vitro , combination of HCT and UVB irradiation did not induce the expression of oxidative stress marker proteins, inflammatory proteins, apoptotic proteins or activation of oncoproteins. CONCLUSION: HCT did not increase photosensitivity for UVA or UVB in healthy volunteers compared with placebo, and was not associated with phototoxic or carcinogenic reactions. In vitro , HCT was also not associated with phototoxicity or carcinogenesis (NCT04654312).

Impedance-based remote monitoring in patients with heart failure and concomitant chronic kidney disease.

AIMS: Remote monitoring (RM) of thoracic impedance represents an early marker of pulmonary congestion in heart failure (HF). Chronic kidney disease (CKD) may promote fluid overload in HF patients. We investigated whether concomitant CKD affected the efficacy of impedance-based RM in the OptiLink HF trial. METHODS AND RESULTS: Among HF patients included in the OptiLink HF trial, time to the first cardiovascular hospitalization and all-cause death according to the presence of concomitant CKD was analysed. CKD was defined as GFR < 60 mL/min/1.73 m2 at enrolment. Of the 1002 patients included in OptiLink HF, 326 patients (33%) had HF with concomitant CKD. The presence of CKD increased transmission of telemedical alerts (median of 2 (1-5) vs. 1 (0-3); P = 0.012). Appropriate contacting after alert transmission was equally low in patients with and without CKD (57% vs. 59%, P = 0.593). The risk of the primary endpoint was higher in patients with CKD compared with patients without CKD (hazard ratio (HR), 1.62 [95% confidence interval (CI), 1.16-2.28]; P = 0.005). Impedance-based RM independently reduced primary events in HF patients with preserved renal function, but not in those with CKD (HR 0.68 [95% CI, 0.52-0.89]; P = 0.006). CONCLUSIONS: The presence of CKD in HF patients led to a higher number of telemedical alert transmissions and increased the risk of the primary endpoint. Inappropriate handling of alert transmission was commonly observed in patients with chronic HF and CKD. Guidance of HF management by impedance-based RM significantly decreased primary event rates in patients without CKD, but not in patients with CKD.

Interventional therapies for pulmonary embolism.

Pulmonary embolism (PE) is the leading cause of in-hospital death and the third most frequent cause of cardiovascular death. The clinical presentation of PE is variable, and choosing the appropriate treatment for individual patients can be challenging. Traditionally, treatment of PE has involved a choice of anticoagulation, thrombolysis or surgery; however, a range of percutaneous interventional technologies have been developed that are under investigation in patients with intermediate-high-risk or high-risk PE. These interventional technologies include catheter-directed thrombolysis (with or without ultrasound assistance), aspiration thrombectomy and combinations of the aforementioned principles. These interventional treatment options might lead to a more rapid improvement in right ventricular function and pulmonary and/or systemic haemodynamics in particular patients. However, evidence from randomized controlled trials on the safety and efficacy of these interventions compared with conservative therapies is lacking. In this Review, we discuss the underlying pathophysiology of PE, provide assistance with decision-making on patient selection and critically appraise the available clinical evidence on interventional, catheter-based approaches for PE treatment. Finally, we discuss future perspectives and unmet needs.

Association of hydrochlorothiazide treatment compared with alternative diuretics with overall and skin cancer risk: a propensity-matched cohort study.

INTRODUCTION: Hydrochlorothiazide (HCT) has been suggested to induce photosensitivity, thereby increasing the incidence of skin cancers. After a pharmacovigilance alert, HCT was frequently withdrawn or substituted by other diuretics. The aim of this study was to compare the association of exposure to HCT with cancer risk versus alternative diuretics. METHODS: A retrospective cohort study was conducted based on data from the AOK PLUS, a large German statutory health insurance fund. Patients with HCT treatment were propensity score matching to patients using non-HCT diuretics. Incidence of cancer of any kind and, specifically, skin cancer was assessed in both groups. Time-to-incident cancer diagnosis was evaluated and compared between the groups. RESULTS: A total of 199 708 patients were included in the final analysis ( n  = 76 855 in the HCT group; n  = 122 853 in the non-HCT-diuretics group). After propensity score matching, 122 554 patients remained in the sample ( n  = 61 277 for both groups, of which >96% had hypertension, mean age 73 years, 61% female). HCT treatment was associated with a lower incidence of cancer of any kind compared with non-HCT diuretics (incidence rate ratio per 100 patient years 0.84 95% confidence interval: 0.82-0.87). HCT treatment was associated with a small albeit significantly higher incidence rate ratio of skin cancer (1.15 95% confidence interval: 1.06-1.24) with significant variances over time. Although numerically higher, the difference accounts to only 0.05 more skin cancer diagnoses in 100 patient-years. CONCLUSION: HCT treatment compared with alternative diuretics was associated with a lower all-cancer risk and a numerically small increased skin cancer risk in a large German population. Risk-benefit evaluation should be executed in patients with increased skin cancer risk and treatment with HCT. Furthermore, advice for skin protection is warranted in all patients taking thiazide or thiazide-like diuretics.

Endovascular Ultrasound Renal Denervation to Treat Hypertension: The RADIANCE II Randomized Clinical Trial.

Importance: Two initial sham-controlled trials demonstrated that ultrasound renal denervation decreases blood pressure (BP) in patients with mild to moderate hypertension and hypertension that is resistant to treatment. Objective: To study the efficacy and safety of ultrasound renal denervation without the confounding influence of antihypertensive medications in patients with hypertension. Design, Setting, and Participants: Sham-controlled, randomized clinical trial with patients and outcome assessors blinded to treatment assignment that was conducted between January 14, 2019, and March 25, 2022, at 37 centers in the US and 24 centers in Europe, with randomization stratified by center. Patients aged 18 years to 75 years with hypertension (seated office systolic BP [SBP] ≥140 mm Hg and diastolic BP [DBP] ≥90 mm Hg despite taking up to 2 antihypertensive medications) were eligible if they had an ambulatory SBP/DBP of 135/85 mm Hg or greater and an SBP/DBP less than 170/105 mm Hg after a 4-week washout of their medications. Patients with an estimated glomerular filtration rate of 40 mL/min/1.73 m2 or greater and with suitable renal artery anatomy were randomized 2:1 to undergo ultrasound renal denervation or a sham procedure. Patients were to abstain from antihypertensive medications until the 2-month follow-up unless prespecified BP criteria were exceeded and were associated with clinical symptoms. Interventions: Ultrasound renal denervation vs a sham procedure. Main Outcomes and Measures: The primary efficacy outcome was the mean change in daytime ambulatory SBP at 2 months. The primary safety composite outcome of major adverse events included death, kidney failure, and major embolic, vascular, cardiovascular, cerebrovascular, and hypertensive events at 30 days and renal artery stenosis greater than 70% detected at 6 months. The secondary outcomes included mean change in 24-hour ambulatory SBP, home SBP, office SBP, and all DBP parameters at 2 months. Results: Among 1038 eligible patients, 150 were randomized to ultrasound renal denervation and 74 to a sham procedure (mean age, 55 years [SD, 9.3 years]; 28.6% female; and 16.1% self-identified as Black or African American). The reduction in daytime ambulatory SBP was greater with ultrasound renal denervation (mean, -7.9 mm Hg [SD, 11.6 mm Hg]) vs the sham procedure (mean, -1.8 mm Hg [SD, 9.5 mm Hg]) (baseline-adjusted between-group difference, -6.3 mm Hg [95% CI, -9.3 to -3.2 mm Hg], P < .001), with a consistent effect of ultrasound renal denervation throughout the 24-hour circadian cycle. Among 7 secondary BP outcomes, 6 were significantly improved with ultrasound renal denervation vs the sham procedure. No major adverse events were reported in either group. Conclusions and Relevance: In patients with hypertension, ultrasound renal denervation reduced daytime ambulatory SBP at 2 months in the absence of antihypertensive medications vs a sham procedure without postprocedural major adverse events. Trial Registration: ClinicalTrials.gov Identifier: NCT03614260.

Hypertension management in patients with cardiovascular comorbidities.

Arterial hypertension is a leading cause of death globally. Due to ageing, the rising incidence of obesity, and socioeconomic and environmental changes, its incidence increases worldwide. Hypertension commonly coexists with Type 2 diabetes, obesity, dyslipidaemia, sedentary lifestyle, and smoking leading to risk amplification. Blood pressure lowering by lifestyle modifications and antihypertensive drugs reduce cardiovascular (CV) morbidity and mortality. Guidelines recommend dual- and triple-combination therapies using renin-angiotensin system blockers, calcium channel blockers, and/or a diuretic. Comorbidities often complicate management. New drugs such as angiotensin receptor-neprilysin inhibitors, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonists improve CV and renal outcomes. Catheter-based renal denervation could offer an alternative treatment option in comorbid hypertension associated with increased sympathetic nerve activity. This review summarises the latest clinical evidence for managing hypertension with CV comorbidities.

Study Evaluating the Use of RenalGuard to Protect Patients at High Risk of AKI.

BACKGROUND: Contrast-induced nephropathy (CIN) can occur after cardiovascular procedures using contrast media, which is associated with increased morbidity and mortality. RenalGuard is a closed-loop system designed to match intravenous hydration with diuretic-induced diuresis that has shown mixed results in the prevention of CIN in previous randomized controlled trials. OBJECTIVES: The STRENGTH (Study Evaluating the Use of RenalGuard to Protect Patients at High Risk of AKI) study assessed whether RenalGuard (PLC Medical Systems) is superior to standard intravenous hydration for CIN prevention in patients with chronic kidney disease undergoing complex cardiovascular procedures. METHODS: STRENGTH is a multicenter, international, open-label, postmarket, prospective, randomized (1:1) study monitored by the Cardiovascular European Research Center (Massy, France) that included a total of 259 patients with moderate to severe chronic kidney disease (estimated glomerular filtration 15-40 mL/min/m2) requiring a complex coronary, structural, or peripheral procedure with an expected contrast injection of at least 3 times the estimated glomerular filtration rate. Patients were randomized to either RenalGuard or intravenous saline hydration according to current guidelines. RESULTS: The primary endpoint, the incidence of CIN at day 3 after the procedure, was similar between the 2 groups (17/107 [15.9%] in the RG group vs 15/110 [13.9%] in the control group; P = 0.62). In addition, none of the secondary endpoints differed between the 2 groups. CONCLUSIONS: In high-risk patients undergoing complex cardiovascular interventions in experienced centers, furosemide-induced high urine output with matched hydration using the RenalGuard system did not reduce the risk of CIN and adverse outcomes at 12 months compared with conventional intravenous hydration.

Comparison of immersive and non-immersive virtual reality videos as substitute for in-hospital teaching during coronavirus lockdown: a survey with graduate medical students in Germany.

As a consequence of the continued Covid-19 lockdown in Germany, in-hospital teaching for medical students was impossible. While lectures and other theoretical training were relatively easily converted into online sessions using platforms such as Moodle, Zoom and Microsoft Teams, this was not the case for practical skills and clinical interventions, such as bronchoscopy or colonoscopy. This study describes a workaround that was implemented at the Saarland University Hospital utilizing virtual reality equipment to convey the impressions of shadowing clinical procedures to the students without physical presence. To achieve this, 3D 180° videos of key clinical interventions of various internal medicine specialities were recorded, cut, and censored. The videos were uploaded to the e-learning YouTube channel of our institution and shared with the students via the private share function. The students could choose whether to use a VR-viewer to watch the videos immersively or to watch them without a viewer on a screen non-immersively. At the end of the course after 1 week, the students completed a questionnaire anonymously focusing on learning-success regarding the presented topics, a self-assessment, and an evaluation of the course. A total of 27 students watched the videos with a VR-Viewer and 74 watched non-immersively. Although the VR-viewer group self-assessed their expertise higher, there was no significant difference between the two groups in the learning-success test score. However, students in the VR-viewer group rated the learning atmosphere, comprehensibility, and overall recommendation of the course significantly higher. They also agreed significantly more to the statement, that they gained a better conception of the presented procedures, and that virtual reality might be an appropriate tool for online teaching. Video-assisted teaching facilitates learning and might be a valuable add-on to conventional teaching.Abbreviations: Covid-19: severe acute respiratory syndrome coronavirus 2; 3D: three-dimensional; 2D: Two-dimensional; VR: virtual reality.

Arterial hypertension - clinical trials update 2022.

Hypertension is the most prevalent cardiovascular risk factor worldwide and is associated with increased cardiovascular morbidity and mortality. Despite the availability of multimodal therapeutic approaches, a large number of patients do not achieve guideline-recommended blood pressure targets, which reiterates the importance of continued research in the field. This article summarizes and discusses the most relevant clinical trials in hypertension research published in 2021 and 2022. The topics include new insights into treatment targets in the elderly, novel findings of salt consumption and lifestyle interventions in resistant hypertension, new evidence about early antihypertensive combination therapy and the use of angiotensin II receptor blocker neprilysin inhibitors in resistant hypertension, as well as data regarding the safety of antihypertensive drugs with respect to cancerogeneity and regarding the impact of acetaminophen, a commonly used pain medication, on blood pressure. Finally, we provide an update on recent evidence on renal denervation and its role in current hypertension management.

Photoinduced skin reactions of cardiovascular drugs-a systematic review.

This systemic review aims to provide a practical overview of the prevalence, clinical manifestation, and management of adverse photoinduced skin reactions caused by frequently used cardiovascular drugs and to assess their potential relevance for skin cancer development. Data search included PubMed, Web of Science, and the Cochrane Library. A systematic review of peer-reviewed studies reporting the photosensitizing and/or skin cancer-inducing properties of common cardiovascular drugs was performed and a guide to clinical management of photoinduced skin eruptions by cardiovascular drugs was provided. Study quality was assessed for major methodological biases. A total of 58 studies were identified (i.e. 23 case reports, 14 observational studies, 10 review articles, 10 experimental studies, and 1 meta-analysis). Most commonly, drug-associated adverse photoinduced cutaneous reactions were caused by phototoxic and photoallergic mechanisms. There is evidence suggesting that amiodarone and dronedarone, thiazide diuretics, thiazide-like diuretics, angiotensin receptor blockers, dihydropyridine-type calcium channel blockers, and certain angiotensin-converting enzyme inhibitors and statins may cause photoinduced adverse cutaneous reactions. Other drugs such as anticoagulants, antiplatelets, aldosterone antagonists, and fibrates have not been linked with photosensitizing reactions or adverse cutaneous reactions. Some drugs, i.e. thiazides and thiazide-like diuretics, were associated with an increased risk of non-melanoma skin cancers (basal cell carcinoma and squamous cell carcinoma). Certain commonly used cardiovascular drugs have been associated with adverse photoinduced cutaneous reactions. If they occur, further diagnosis and treatment might be needed, depending on the severity and progress. Whether photosensitizing drugs increase the risk of skin cancer remains elusive and further randomized controlled trials are required.

Drug-coated balloons for small coronary artery disease in patients with chronic kidney disease: a pre-specified analysis of the BASKET-SMALL 2 trial.

BACKGROUND: Data on the safety and efficacy of drug-coated balloon (DCB) compared to drug-eluting stent (DES) in patients with chronic kidney disease (CKD) are scarce, particularly at long term. This pre-specified analysis aimed to investigate the 3-year efficacy and safety of DCB versus DES for small coronary artery disease (< 3 mm) according to renal function at baseline. METHODS: BASKET-SMALL-2 was a large multi-center, randomized, controlled trial that tested the efficacy and safety of DCBs (n = 382) against DESs (n = 376) in small vessel disease. CKD was defined as eGFR < 60 ml/min/1.73m2. The primary endpoint was the composite of cardiac death, non-fatal myocardial infarction, and target vessel revascularization (MACE) during 3 years. RESULTS: A total of 174/758 (23%) patients had CKD, out of which 91 were randomized to DCB and 83 to DES implantation. The primary efficacy outcome during 3 years was similar in both, DCB and DES patients (HR 0.98; 95%-CI 0.67-1.44; p = 0.937) and patients with and without CKD (HR 1.18; 95%-CI 0.76-1.83; p = 0.462), respectively. Rates of cardiac death and all-cause death were significantly higher among patients with CKD but not affected by treatment with DCB or DES. Major bleeding events were lower in the DCB when compared to the DES group (12 vs. 3, HR 0.26; 95%-CI 0.07-0.92; p = 0.037) and not influenced by presence of CKD. CONCLUSIONS: The long-term efficacy and safety of DCB was similar in patients with and without CKD. The use of DCB was associated with significantly fewer major bleeding events (NCT01574534). Central Illustration. Drug-coated balloon versus drug-eluting stents in small coronary artery disease with and without chronic kidney disease, a prespecified subgroup analysis of the BASKET-SMALL 2 trial.

Renal Artery Variations in Patients With Mild-to-Moderate Hypertension From the RADIANCE-HTN SOLO Trial.

PURPOSE: To assess the variability of renal artery (RA) anatomy and presence of RA-pathology in patients with mild-to-moderate hypertension enrolled in the RADIANCE-HTN SOLO trial. BACKGROUND: RADIANCE-HTN SOLO was a multicenter, international, blinded, randomized, sham-controlled trial evaluating ultrasound-based endovascular renal denervation (RDN) in patients with mild-to-moderate hypertension while off antihypertensive medications. METHODS: Eligible subjects had pre-randomization renal CT- or MR- angiography (CTA, MRA) to confirm anatomic suitability and to define RA ablation sites. All images were sent for independent review for evaluation of RA anatomy and other vascular pathology. RESULTS: A total of 324 patients underwent RA imaging (282 CTA and 42 MRA). Of those, 178 had simple anatomy with a single left and single right RA with mean diameters of 5.4 ± 0.9 and 5.1 ± 0.8 mm and mean lengths of 40.0 ± 12.9 and 52.0 ± 13.1 mm, respectively. Twenty-seven patients (8.3%) had unilateral or bilateral dual RAs with mean diameters of 4.0 ± 0.9 mm on the left and 3.9 ± 0.9 mm on the right. Forty percent (129/324) of patients had at least 1 accessory RA, with mean accessory diameters of 2.4 ± 0.8 mm on the left and 2.3 ± 0.8 mm on the right. Twenty-eight patients (8.6%) had at least 1 short (<25 mm) main RA. Incidental findings included: 9 patients (2.8%) with atherosclerotic RA stenosis ≥30%, 9 patients (2.8%) with fibromuscular dysplasia of RA and 2 patients (0.6%) with kidney and adrenal gland tumors. CONCLUSIONS: Pre-procedure CTA or MRA imaging is a valuable aid in assessing RA anatomy prior to RDN because of variable RA anatomy. CTA or MRA may detect RA lesions, and renal or adrenal tumors which may need additional workup prior to consideration of RDN. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02649426.

Blood pressure lowering with alcohol-mediated renal denervation using the Peregrine infusion Catheter is independent of injection site location.

OBJECTIVES: The current analysis utilized core laboratory angiographic data from a prospective, single-arm, open-label, multi-center feasibility study to ascertain whether the location of alcohol infusion within main renal arteries during renal denervation (RDN) had an impact on the BP-lowering effect at 6 months. BACKGROUND: The influence of the location of alcohol infusion during RDN, within the main renal artery (proximal, middle, or distal), on the magnitude of the blood pressure (BP) lowering is unstudied. METHODS: The Peregrine Catheter was used to perform alcohol-mediated RDN with an infusion of 0.6 mL of alcohol per artery as the neurolytic agent in 90 main arteries and four accessory arteries of 45 patients with hypertension. RESULTS: No relationship between the site of alcohol infusion and change from baseline in both office systolic and 24-hour systolic ambulatory BP (ABP) at 6 months was observed. When analyzed at the artery level, the least squares (LS) mean changes ± SEM from baseline to 6 months post-procedure in 24-hour systolic ABP when analyzed by renal arterial location were -11.9 ± 2.4 mmHg (distal), -10 ± 1.6 mmHg (middle), and -10.6 ± 1.3 mmHg (proximal) (all p < 0.0001 for change from baseline within groups). The results were similar for office systolic BP. There was no difference between treated locations (proximal is reference). CONCLUSION: In this post-hoc analysis, the location of alcohol infusion within the main renal artery using the Peregrine system, with alcohol as the neurolytic agent for chemical RDN, did not affect the magnitude of BP changes at 6 months.

Catheter-based alcohol-mediated renal denervation for the treatment of uncontrolled hypertension: design of two sham-controlled, randomized, blinded trials in the absence (TARGET BP OFF-MED) and presence (TARGET BP I) of antihypertensive medications.

BACKGROUND: Arterial hypertension is a common and life-threatening condition and poses a large global health burden. Device-based treatments have been developed as adjunctive or alternative therapy, to be used with or without antihypertensive medication for treating uncontrolled hypertension. The safety and feasibility of chemical renal denervation (RDN) using the Peregrine Catheter and alcohol were demonstrated in a first-in-man and open-label clinical trials, prompting the initiation of the ongoing TARGET BP OFF-MED and TARGET BP I trials. DESIGN: The TARGET BP trials are randomized, blinded, sham-controlled trials designed to assess the safety and efficacy of alcohol-mediated RDN for the treatment of uncontrolled hypertension in the absence of antihypertensive medications (TARGET BP OFF-MED) or in addition to prescribed antihypertensive medications (TARGET BP I). Subjects with confirmed uncontrolled hypertension and suitable renal artery anatomy are randomized (1:1) to receive either RDN using the Peregrine Kit with alcohol (0.6 mL per renal artery) infused through the Peregrine Catheter or diagnostic renal angiography only (sham procedure). TARGET BP OFF-MED completed enrollment and randomized 96 subjects. TARGET BP I will randomize approximately 300 subjects and will transition to an open-label safety cohort of approximately 300 subjects receiving RDN once the primary efficacy endpoint of the Randomized Controlled Trial (RCT) cohort has been met. Primary endpoints are change in mean 24-hour ambulatory systolic blood pressure from baseline to 8 weeks (TARGET BP OFF-MED) and 3 months (TARGET BP I) post-procedure. CONCLUSION: The TARGET BP trials are the first large-scale, international, randomized trials aimed to investigate the safety and BP lowering efficacy of a novel RDN method, with perivascular alcohol delivery using the Peregrine Kit.

Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial.

BACKGROUND: Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications. METHODS: In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426. FINDINGS: Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups. INTERPRETATION: Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension. FUNDING: ReCor Medical.

Extra-cardiac targets in the management of cardiometabolic disease: Device-based therapies.

Heart failure (HF) does not occur in a vacuum and is commonly defined and exacerbated by its co-morbid conditions. Neurohormonal imbalance and systemic inflammation are some of the key pathomechanisms of HF but also commonly encountered co-morbidities such as arterial hypertension, diabetes mellitus, cachexia, obesity and sleep-disordered breathing. A cornerstone of HF management is neurohormonal blockade, which in HF with reduced ejection fraction has been tied to a reduction in morbidity and mortality. Pharmacological treatment effective in patients with HF with reduced ejection fraction did not show substantial effects in HF with preserved ejection fraction. Here, we review novel device-based therapies using neuromodulation of extra-cardiac targets to treat cardiometabolic disease.