Publications by authors named "Alexandre Persu"

154 Publications

Prevalence and Disease Spectrum of Extracoronary Arterial Abnormalities in Spontaneous Coronary Artery Dissection.

JAMA Cardiol 2021 Nov 24. Epub 2021 Nov 24.

Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom.

Importance: Spontaneous coronary artery dissection (SCAD) has been associated with fibromuscular dysplasia (FMD) and other extracoronary arterial abnormalities. However, the prevalence, severity, and clinical relevance of these abnormalities remain unclear.

Objective: To assess the prevalence and spectrum of FMD and other extracoronary arterial abnormalities in patients with SCAD vs controls.

Design, Setting, And Participants: This case series included 173 patients with angiographically confirmed SCAD enrolled between January 1, 2015, and December 31, 2019. Imaging of extracoronary arterial beds was performed by magnetic resonance angiography (MRA). Forty-one healthy individuals were recruited to serve as controls for blinded interpretation of MRA findings. Patients were recruited from the UK national SCAD registry, which enrolls throughout the UK by referral from the primary care physician or patient self-referral through an online portal. Participants attended the national SCAD referral center for assessment and MRA.

Exposures: Both patients with SCAD and healthy controls underwent head-to-pelvis MRA (median time between SCAD event and MRA, 1 [IQR, 1-3] year).

Main Outcome And Measures: The diagnosis of FMD, arterial dissections, and aneurysms was established according to the International FMD Consensus. Arterial tortuosity was assessed both qualitatively (presence or absence of an S curve) and quantitatively (number of curves ≥45%; tortuosity index).

Results: Of the 173 patients with SCAD, 167 were women (96.5%); mean (SD) age at diagnosis was 44.5 (7.9) years. The prevalence of FMD was 31.8% (55 patients); 16 patients (29.1% of patients with FMD) had involvement of multiple vascular beds. Thirteen patients (7.5%) had extracoronary aneurysms and 3 patients (1.7%) had dissections. The prevalence and degree of arterial tortuosity were similar in patients and controls. In 43 patients imaged with both computed tomographic angiography and MRA, the identification of clinically significant remote arteriopathies was similar. Over a median 5-year follow-up, there were 2 noncardiovascular-associated deaths and 35 recurrent myocardial infarctions, but there were no primary extracoronary vascular events.

Conclusions And Relevance: In this case series with blinded analysis of patients with SCAD, severe multivessel FMD, aneurysms, and dissections were infrequent. The findings of this study suggest that, although brain-to-pelvis imaging allows detection of remote arteriopathies that may require follow-up, extracoronary vascular events appear to be rare.
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http://dx.doi.org/10.1001/jamacardio.2021.4690DOI Listing
November 2021

Adherence to antihypertensive drug treatment in kidney transplant recipients.

Blood Press 2021 Nov 18:1-5. Epub 2021 Nov 18.

Department of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

Purpose: Hypertension is a common cardiovascular co-morbidity after kidney transplantation and contributes to shortened graft and patient survival outcomes. However, by contrast with adherence to immunosuppressive drugs, adherence to antihypertensive treatment in kidney transplant recipients has been seldom explored. The aim of the current study was to assess adherence to antihypertensive drugs in kidney transplant recipients from the Cliniques Universitaires Saint-Luc and to look for demographic and clinical characteristics associated with drug adherence.

Methods: Demographic and clinical data were collected from medical files in a standardised case report form. Blood pressure was measured in the sitting position after 5 min rest, using validated oscillometric devices. Drug adherence was assessed by drug dosage in urine using liquid chromatography coupled with tandem mass spectrometry.

Results: Our analysis included 53 kidney transplants recipients (75% of men, mean age: 57.2 ± 12.6 years, time since kidney transplantation: 9.5 ± 7.3 years, blood pressure: 130 ± 16/78 ± 11 mmHg on 2.1 ± 1.1 antihypertensive drugs). The proportion of patients showing full drug adherence, partial drug adherence, and total non-adherence to antihypertensive drugs was 79% ( = 42), 15% ( = 8), and 6% ( = 3), respectively. Adherent patients did not differ from less or non- adherers in any of the analysed characteristics.

Conclusion: The proportion of patients adhering to antihypertensive drug treatment among kidney transplant recipients appears similar to that reported for immunosuppressive drugs in renal transplanted patients (∼70%), but much higher than that observed in patients with drug-resistant hypertension (30-40%). Our results need further confirmation in a large, multicenter, prospective cohort.
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http://dx.doi.org/10.1080/08037051.2021.2004087DOI Listing
November 2021

Increased Collagen Turnover Is a Feature of Fibromuscular Dysplasia and Associated With Hypertrophic Radial Remodeling: A Pilot, Urine Proteomic Study.

Hypertension 2021 Nov 17:HYPERTENSIONAHA12118146. Epub 2021 Nov 17.

Division of Cardiology, Cliniques Universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium (M.P.,C.B., A.P.).

Fibromuscular dysplasia (FMD), a nonatherosclerotic, noninflammatory disease of medium-sized arteries, is an underdiagnosed disease. We investigated the urinary proteome and developed a classifier for discrimination of FMD from healthy controls and other diseases. We further hypothesized that urinary proteomics biomarkers may be associated with alterations in medium-sized, but not large artery geometry and mechanics. The study included 33 patients with mostly multifocal, renal FMD who underwent in depth arterial exploration using ultra-high frequency ultrasound. The cohort was separated in a training set of 23 patients with FMD from Belgium and an independent test set of 10 patients with FMD from Italy. For each set, controls matched 2:1 were selected from the Human Urinary Proteome Database. The specificity of the classifier was tested in 700 additional controls from general population studies, patients with chronic kidney disease (n=66) and coronary artery disease (n=31). Three hundred thirty-five urinary peptides, mostly related to collagen turnover, were identified in the training cohort and combined into a classifier. When applying in the test cohort, the area under the receiver operating characteristic curve was 1.00, 100% specificity at 100% sensitivity. The classifier maintained a high specificity in additional controls (98.3%), patients with chronic kidney (90.9%) and coronary artery (96.8%) diseases. Furthermore, in patients with FMD, the proteomic score was positively associated with radial wall thickness and wall cross-sectional area. In conclusion, a proteomic score has the potential to discriminate between patients with FMD and controls. If confirmed in a wider and more diverse cohort, these findings may pave the way for a noninvasive diagnostic test of FMD.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.18146DOI Listing
November 2021

Nonadherence in Hypertension: How to Develop and Implement Chemical Adherence Testing.

Hypertension 2021 Nov 5:HYPERTENSIONAHA12117596. Epub 2021 Nov 5.

Renal Unit, Heartlands Hospital, Birmingham and Warwick Medical School, University of Warwick, Coventry, United Kingdom (I.D.).

Nonadherence to antihypertensive medication is common, especially in those with apparent treatment-resistant hypertension (true treatment-resistant hypertension requires exclusion of nonadherence), and its routine detection is supported by clinical guidelines. Chemical adherence testing is a reliable and valid method to detect adherence, yet methods are unstandardized and are not ubiquitous. This article describes the principles of chemical adherence testing for hypertensive patients and provides a set of recommendations for centers wishing to develop the test. We recommend testing should be done in either of two instances: (1) in those who have resistant hypertension or (2) in those on 2 antihypertensives who have a less than 10 mm Hg drop in systolic blood pressure on addition of the second antihypertensive medication. Furthermore, we recommend that verbal consent is secured before undertaking the test, and the results should be discussed with the patient. Based on medications prescribed in United Kingdom, European Union, and United States, we list top 20 to 24 drugs that cover >95% of hypertension prescriptions which may be included in the testing panel. Information required to identify these medications on mass spectrometry platforms is likewise provided. We discuss issues related to ethics, sample collection, transport, stability, urine versus blood samples, qualitative versus quantitative testing, pharmacokinetics, instrumentation, validation, quality assurance, and gaps in knowledge. We consider how to best present, interpret, and discuss chemical adherence test results with the patient. In summary, this guidance should help clinicians and their laboratories in the development of chemical adherence testing of prescribed antihypertensive drugs.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17596DOI Listing
November 2021

Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases.

Nat Commun 2021 10 15;12(1):6031. Epub 2021 Oct 15.

Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.

Fibromuscular dysplasia (FMD) is an arteriopathy associated with hypertension, stroke and myocardial infarction, affecting mostly women. We report results from the first genome-wide association meta-analysis of six studies including 1556 FMD cases and 7100 controls. We find an estimate of SNP-based heritability compatible with FMD having a polygenic basis, and report four robustly associated loci (PHACTR1, LRP1, ATP2B1, and LIMA1). Transcriptome-wide association analysis in arteries identifies one additional locus (SLC24A3). We characterize open chromatin in arterial primary cells and find that FMD associated variants are located in arterial-specific regulatory elements. Target genes are broadly involved in mechanisms related to actin cytoskeleton and intracellular calcium homeostasis, central to vascular contraction. We find significant genetic overlap between FMD and more common cardiovascular diseases and traits including blood pressure, migraine, intracranial aneurysm, and coronary artery disease.
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http://dx.doi.org/10.1038/s41467-021-26174-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521585PMC
October 2021

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

Catheter Cardiovasc Interv 2021 11 2;98(6):E832-E838. Epub 2021 Sep 2.

Department of Medicine, CardioVascular Center Frankfurt, Frankfurt, Germany.

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.
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http://dx.doi.org/10.1002/ccd.29936DOI Listing
November 2021

Long-Term Results up to 12 Months After Catheter-Based Alcohol-Mediated Renal Denervation for Treatment of Resistant Hypertension.

Circ Cardiovasc Interv 2021 09 2;14(9):e010075. Epub 2021 Sep 2.

Division of Cardiology, Department of Cardiovascular Diseases, Cliniques Universitaires Saint-Luc and Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium (J.-P.L., A.P.).

[Figure: see text].
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.120.010075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452324PMC
September 2021

Beyond Atherosclerosis and Fibromuscular Dysplasia: Rare Causes of Renovascular Hypertension.

Hypertension 2021 Sep 30;78(4):898-911. Epub 2021 Aug 30.

Department of Hypertension, National Institute of Cardiology, Warsaw, Poland (A.P., P.D., M.J., A.J.).

Renovascular hypertension is one of the most common forms of secondary hypertension. Over 95% of cases of renovascular hypertension are due either to atherosclerosis of the main renal artery trunks or to fibromuscular dysplasia. These two causes of renal artery stenosis have been extensively discussed in recent reviews and consensus. The aim of the current article is to provide comprehensive and up-to-date information on the remaining causes. While these causes are rare or extremely rare, etiologic and differential diagnosis matters both for prognosis and management. Therefore, the clinician cannot ignore them. For didactic reasons, we have grouped these different entities into stenotic lesions (neurofibromatosis type 1 and other rare syndromes, dissection, arteritis, and segmental arterial mediolysis) often associated with aortic coarctation and other arterial abnormalities, and nonstenotic lesions, where hypertension is secondary to compression of adjacent arteries and changes in arterial pulsatility (aneurysm) or to the formation of a shunt, leading to kidney ischemia (arteriovenous fistula). Finally, thrombotic disorders of the renal artery may also be responsible for renovascular hypertension. Although thrombotic/embolic lesions do not represent primary vessel wall disease, they are characterized by frequent macrovascular involvement. In this review, we illustrate the most characteristic aspects of these different entities responsible for renovascular hypertension and discuss their prevalence, pathophysiology, clinical presentation, management, and prognosis.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415524PMC
September 2021

Hypertension healthcare professional beliefs and behaviour regarding patient medication adherence: a survey conducted among European Society of Hypertension Centres of Excellence.

Blood Press 2021 10 14;30(5):282-290. Epub 2021 Aug 14.

Institute of Clinical Pharmacology and Toxicology, Humboldt-Universität zu Berlin, Berlin, Germany.

Purpose: Little is known on the beliefs, perceptions and practices of hypertension specialists in addressing non-adherence to therapy. Therefore, a survey was undertaken amongst healthcare professionals (HCPs) managing hypertension in the European Society of Hypertension (ESH) Centres of Excellence.

Materials And Methods: Cross-sectional data were obtained between December 2020 and April 2021 using an online anonymous structured questionnaire including 26 questions/136 items, that was sent to all ESH Excellence centres.

Results: Overall 67 from 187 centres (37.3%) responded and 200 HCPs from 30 countries answered the questionnaire. Participants (60% men) were mainly physicians (91%) and nurses (8%) from University hospitals (77%). Among physicians, 83% had >10 years professional experience. Average time dedicated to discuss medications was 1-5 min in 48% and 6-10 min in 29% of cases. Interviews with patients about adherence were the most frequently used assessment method. Chemical detection of medications in urine was available in 36% of centres. One third of physicians involved their patients regularly in treatment decisions. The most frequent methods to improve adherence included simplification of medication therapy, more frequent visits, and home blood pressure monitoring.

Conclusions: The level of implementation of tools to detect and improve adherence in hypertension management by HCPs in ESH excellence centres is low. Structured educational activities focussing on adherence management and access to the newest objective measures to detect non-adherence might improve these deficits.
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http://dx.doi.org/10.1080/08037051.2021.1963209DOI Listing
October 2021

European Society of Hypertension position paper on renal denervation 2021.

J Hypertens 2021 09;39(9):1733-1741

National and Kapodistrian University of Athens, 1st Cardiology Clinic, Hippocratio Hospital, Athens, Greece.

This ESH Position Paper 2021 with updated proposed recommendations was deemed necessary after the publication of a set of new pivotal sham-controlled randomized clinical trials (RCTs), which provided important information about the efficacy and safety of endovascular device-based renal denervation (RDN) for hypertension treatment. RDN is effective in reducing or interrupting the sympathetic signals to the kidneys and decreasing whole body sympathetic activity. Five independent, fully completed, sham-controlled RCTs provide conclusive evidence that RDN lowers ambulatory and office blood pressure (BP) to a significantly greater extent than sham treatment. BP-lowering efficacy is evident both in patients with and without concomitant antihypertensive medication. The average decrease of 10 mmHg in office BP is estimated to lower the incidence of cardiovascular events by 25-30%, based on meta-analyses of RCTs using pharmacological treatment. Neither peri-procedural, nor short-term or long-term adverse events or safety signals (available up to 3 years) have been observed. Implementing RDN as an innovative third option in the armamentarium of antihypertensive treatment requires a structured process that ensures the appropriate performance of the endovascular RDN procedure and adequate selection of hypertensive patients. The latter should also incorporate patients' perspective and preference that needs to be respected in a shared decision-making process.
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http://dx.doi.org/10.1097/HJH.0000000000002933DOI Listing
September 2021

Fibromuscular dysplasia: its various phenotypes in everyday practice in 2021.

Kardiol Pol 2021;79(7-8):733-744. Epub 2021 Jun 24.

Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique and Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The pathogenesis of FMD remains poorly understood, but a combination of genetic and environmental factors may be involved. The majority of FMD patients are women, but men may have a more progressive disease, especially when smoking. Besides the classical phenotype of string of beads or focal stenosis, arterial aneurysms, dissections, and tortuosity are frequent manifestations of the disease. However, the differential diagnosis of FMD is extensive and includes imaging artefacts as well as other arterial diseases. Diagnosis is based on CT-, MR-, or conventional catheter-based angiography during work-up of clinical manifestations, but clinically silent lesions may be found incidentally. Arterial hypertension and neurological symptoms are the most frequent clinical presentations, as renal and cerebrovascular arteries are the most commonly involved. However, involvement of most arteries throughout the body has been reported, resulting in a variety of clinical symptoms. The management of FMD depends on the vascular phenotype as well on the clinical picture. Ongoing FMD-related research will elaborate in depth the current progress in improved understandings of the disease's clinical manifestations, epidemiology, natural history and pathogenesis. This review is focused on the clinical management of adult FMD in daily practice.
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http://dx.doi.org/10.33963/KP.a2021.0040DOI Listing
September 2021

Combination of acute hypertensive striatocapsular hemorrhage and mirror previous asymptomatic slit-like hemorrhage in a young patient: a new radiological clue for cerebral small vessel disease?

Acta Neurol Belg 2021 Oct 23;121(5):1371-1373. Epub 2021 Jun 23.

Neuroradiology Unit, Department of Radiology, Cliniques Universitaires Saint-Luc, avenue Hippocrate 10, 1200, Brussels, Belgium.

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http://dx.doi.org/10.1007/s13760-021-01725-yDOI Listing
October 2021

Baseline Brain-to-Pelvis Imaging Predicts Subsequent Arterial Complications in Patients With Renal Artery Dissection.

Hypertension 2021 07 9;78(1):62-64. Epub 2021 Jun 9.

Division of Cardiology, Cliniques Universitaires Saint-Luc and Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium (A.P., S.C., M.P.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17294DOI Listing
July 2021

Hypertension in kidney transplantation: a consensus statement of the 'hypertension and the kidney' working group of the European Society of Hypertension.

J Hypertens 2021 08;39(8):1513-1521

Associazione Ipertensione, Nefrologia e Trapianto Renal (IPNET) C/O CNR-IFC, Ospedali Riuniti, Reggio Calabria, Italy.

Hypertension is common in kidney transplantation recipients and may be difficult to treat. Factors present before kidney transplantation, related to the transplantation procedure itself and factors developing after transplantation may contribute to blood pressure (BP) elevation in kidney transplant recipients. The present consensus is based on the results of three recent systematic reviews, the latest guidelines and the current literature. The current transplant guidelines, which recommend only office BP assessments for risk stratification in kidney transplant patients should be reconsidered, given the presence of white-coat hypertension and masked hypertension in this population and the better prediction of adverse outcomes by 24-h ambulatory BP monitoring as indicated in recent systematic reviews. Hypertension is associated with adverse kidney and cardiovascular outcomes and decreased survival in kidney transplant recipients. Current evidence suggests calcium channel blockers could be the preferred first-step antihypertensive agents in kidney transplant patients, as they improve graft function and reduce graft loss, whereas no clear benefit is documented for renin-angiotensin system inhibitor use over conventional treatment in the current literature. Randomized control trials demonstrating the clinical benefits of BP lowering on kidney and major cardiovascular events and recording patient-related outcomes are still needed. These trials should define optimal BP targets for kidney transplant recipients. In the absence of kidney transplant-specific evidence, BP targets in kidney transplant recipients should be similar to those in the wider chronic kidney disease population.
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http://dx.doi.org/10.1097/HJH.0000000000002879DOI Listing
August 2021

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.

Am Heart J 2021 09 27;239:90-99. Epub 2021 May 27.

Piedmont Heart Institute, Atlanta, GA.

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.
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http://dx.doi.org/10.1016/j.ahj.2021.05.015DOI Listing
September 2021

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

Lancet 2021 Jun 16;397(10293):2476-2486. Epub 2021 May 16.

Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, NY, USA.

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.
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http://dx.doi.org/10.1016/S0140-6736(21)00788-1DOI Listing
June 2021

Kidney donors with fibromuscular dysplasia, is it time to open the doors?

Nephrol Dial Transplant 2021 07;36(8):1365-1368

Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

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http://dx.doi.org/10.1093/ndt/gfab181DOI Listing
July 2021

Male Sex Is Associated With Cervical Artery Dissection in Patients With Fibromuscular Dysplasia.

J Am Heart Assoc 2021 06 17;10(11):e018311. Epub 2021 May 17.

Department of Neurology Inserm U1237 Normandie UniversitéUniversité Caen NormandieCHU Caen Normandie Caen France.

Background Cervical artery dissection (CeAD) is a frequent manifestation of fibromuscular dysplasia (FMD). However, risk factors for CeAD are unknown. We investigated factors associated with CeAD in the ARCADIA (Assessment of Renal and Cervical Artery Dysplasia) registry. Methods and Results The ARCADIA registry includes women or men aged ≥18 years, with a diagnosis of renal, cervical, or intracranial artery FMD, who were prospectively recruited at 16 university hospitals in France and Belgium. Diagnosis of acute or past CeAD at inclusion was established on imaging according to standard diagnostic criteria. Associations between potential determinants and CeAD were assessed by logistic regression analyses. Among 469 patients (75 men) with FMD, 65 (13.9%) had CeAD. Patients with CeAD were younger, more likely to be men, have a history of migraine, and less likely to have a history of hypertension than patients without CeAD. In the multivariable analysis, male sex (odds ratio [OR], 2.66; 95% CI, 1.34-5.25), history of migraine (OR, 1.90; 95% CI, 1.06-3.39), age ≥50 years (OR, 0.41; 95% CI, 0.23-0.73), history of hypertension (OR, 0.35; 95% CI, 0.20-0.64), and involvement of ≥3 vascular beds (OR, 2.49; 95% CI, 1.15-5.40) were significantly associated with CeAD. To validate the association between CeAD and sex, we performed a systematic review. We collected additional data on sex from 2 published studies and unpublished data from the US Registry for Fibromuscular Dysplasia and the European/International FMD Registry. In the pooled analysis (289 CeAD, 1933 patients), male sex was significantly associated with CeAD (OR, 2.04; 95% CI, 1.41-2.95; =0%). Conclusions In patients with FMD, male sex and multisite involvement are associated with CeAD, in addition to other previously known risk factors. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02884141.
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http://dx.doi.org/10.1161/JAHA.120.018311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483547PMC
June 2021

Mineralocorticoid receptor antagonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease.

Nephrol Dial Transplant 2021 May 4. Epub 2021 May 4.

Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.

Diabetic kidney disease develops in about 40% of patients with diabetes and is the commonest cause of chronic kidney disease worldwide. Patients with chronic kidney disease, especially those with diabetes mellitus, are at high risk of both developing kidney failure and cardiovascular death. The use of renin-angiotensin system blockers to reduce the incidence of kidney failure in patients with diabetic kidney disease dates back to studies that are now 20 or more years old. During the last few years sodium-glucose co-transporter-2 inhibitors have shown beneficial renal effects in randomized trials. However, even in response to combined treatment with renin-angiotensin system blockers and sodium-glucose co-transporter-2 inhibitors, the renal residual risk remains high with kidney failure only deferred, but not avoided. The risk of cardiovascular death also remains high even with optimal current treatment. Steroidal mineralocorticoid receptor antagonists reduce albuminuria and surrogate markers of cardiovascular disease in patients already on optimal therapy. However, their use has been curtailed by the significant risk of hyperkalaemia. In The FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease (FIDELIO-DKD) study comparing the actions of the non-steroidal mineralocorticoid receptor antagonist finerenone with placebo, finerenone reduced the progression of diabetic kidney disease and the incidence of cardiovascular events with a relatively safe adverse event profile. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of mineralocorticoid receptor antagonists, analyses the potential mechanisms involved and discusses their potential future place in the treatment of patients with diabetic chronic kidney disease.
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http://dx.doi.org/10.1093/ndt/gfab167DOI Listing
May 2021

Blood pressure monitoring in kidney transplantation: a systematic review on hypertension and target organ damage.

Nephrol Dial Transplant 2021 Mar 25. Epub 2021 Mar 25.

CNR-Institute of Clinical Physiology; Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension, Reggio Calabria, Italy.

Background: Sparse studies show that ambulatory blood pressure monitoring (ABPM) is superior to office BP (oBP) measurements to predict target organ damage and cardiovascular (CV) events in kidney transplant recipients (KTRs). We performed a systematic review aimed at determining the potential associations between BP recordings by different methods and renal and CV outcomes in this population.

Methods: Major medical databases were searched for studies enrolling adult KTRs undergoing 24h ABPM compared to office or home BP measurements. Main outcomes were: associations between different BP recordings and renal and CV outcomes. Additionally, any association between the circadian BP pattern (dipping/non-dipping status) and outcomes was assessed.

Results: Twenty-two studies (2078 participants) were reviewed. Amongst 12 studies collecting data on renal endpoints, ten studies found that BP assessed by ABPM was a stronger predictor of renal function decline, assessed by serum creatinine (SCr) and/or creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR), than traditional office measurements. Twelve studies analyzed the relation between different BP recordings and CV target organ damages and reported robust correlations between echocardiographic abnormalities [i.e. left ventricular mass index (LVM/LVMI)] and 24h ABPM, but not with office BPs. Furthermore, 24h ABPM correlated better than oBP with markers of vascular damage, such as carotid intima-media thickness (IMT), diffuse thickening, and endothelial dysfunction. Additionally, abnormal circadian BP pattern (non-dippers and reverse dippers) identified a group of kidney recipients at risk for kidney function loss and CV abnormalities.

Conclusions: In our systematic review, ABPM reflected target organ damage more closely than oBP in KTRs. Furthermore, altered circadian BP profile associated with renal and CV target organ damages.
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http://dx.doi.org/10.1093/ndt/gfab076DOI Listing
March 2021

Current progress in clinical, molecular, and genetic aspects of adult fibromuscular dysplasia.

Cardiovasc Res 2021 Mar 19. Epub 2021 Mar 19.

Department of Hypertension, National Institute of Cardiology, Warsaw, Poland.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The majority of FMD patients are women. Although a variety of genetic, mechanical, and hormonal factors play a role in the pathogenesis of FMD, overall, its cause remains poorly understood. It is probable that the pathogenesis of FMD is linked to a combination of genetic and environmental factors. Extensive studies have correlated the arterial lesions of FMD to histopathological findings of arterial fibrosis, cellular hyperplasia, and distortion of the abnormal architecture of the arterial wall. More recently, the vascular phenotype of lesions associated with FMD has been expanded to include arterial aneurysms, dissections, and tortuosity. However, in the absence of a string of beads or focal stenosis, these lesions do not suffice to establish the diagnosis. While FMD most commonly involves renal and cerebrovascular arteries, involvement of most arteries throughout the body has been reported. Increasing evidence highlights that FMD is a systemic arterial disease and that subclinical alterations can be found in non-affected arterial segments. Recent significant progress in FMD-related research which has led to improved understandings of the disease's clinical manifestations, natural history, epidemiology, and genetics. Ongoing work continues to focus on FMD genetics and proteomics, physiological effects of FMD on cardiovascular structure and function, and novel imaging modalities and blood-based biomarkers that can be used to identify subclinical FMD. It is also hoped that the next decade will bring the development of multi-centred and potentially international clinical trials to provide comparative effectiveness data to inform the optimal management of patients with FMD.
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http://dx.doi.org/10.1093/cvr/cvab086DOI Listing
March 2021

2021 European Society of Hypertension practice guidelines for office and out-of-office blood pressure measurement.

J Hypertens 2021 07;39(7):1293-1302

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Clinical Pharmacology and Toxicology, Charité University Medicine, Berlin, Germany.

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http://dx.doi.org/10.1097/HJH.0000000000002843DOI Listing
July 2021

Intrarenal hemodynamics and kidney function in pheochromocytoma and paraganglioma before and after surgical treatment.

Blood Press 2021 06 15;30(3):172-179. Epub 2021 Feb 15.

Department of Hypertension, National Institute of Cardiology, Warsaw, Poland.

Purpose: Current evidence regarding renal involvement in pheochromocytoma and paraganglioma (PPGL) is scant. More accurate diagnostic methods, such as renal Doppler ultrasound for intrarenal hemodynamic studies, may provide more detailed information on renal function. It might be postulated that renal function in PPGL patients might be altered by high blood pressure and excess secretion of catecholamines. The aim of this prospective study was to assess intrarenal blood flow parameters in PPGL patients included in the prospective monoamine-producing tumour (PMT) study and to evaluate the effects of normalisation of catecholamine production after surgical treatment on long-term renal function.

Materials And Methods: Seventy consecutive patients (aged 46.5 ± 14.0 years) with PPGL were included. Forty-eight patients from the PMT study cohort, matched for age, gender, blood pressure level and presence of hypertension, served as a control group. Renal artery doppler ultrasound spectral analysis included mean resistance index (RRI) and pulsatility index (PI). Forty-seven patients completed 12 months follow-up.

Results: There were no differences in renal parameters such as RRI, PI and kidney function between PPGL and non-PPGL patients as assessed by renal ultrasound, serum creatinine, eGFR and albumin excretion rate. No correlations between kidney function parameters, intrarenal doppler flow parameters and plasma catecholamines were observed in PPGL patients. At 12 months after surgery, no differences in creatinine level, eGFR, albumin excretion rate, RI and PI were found as compared to baseline results.

Conclusions: In contrast to patients with other forms of secondary hypertension, our study did not show differences in intrarenal blood flow parameters and renal function between PPGL and non-PPGL subjects. Intrarenal hemodynamics and renal function did not change after normalisation of catecholamine levels by surgical treatment.
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http://dx.doi.org/10.1080/08037051.2020.1851590DOI Listing
June 2021

Starting Antihypertensive Drug Treatment With Combination Therapy: Controversies in Hypertension - Pro Side of the Argument.

Hypertension 2021 03 10;77(3):800-805. Epub 2021 Feb 10.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institut für Klinische Pharmakologie und Toxikologie, Germany. DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany (E.A.E.-H.A., R.K.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.12857DOI Listing
March 2021

Lifestyle, psychological, socioeconomic and environmental factors and their impact on hypertension during the coronavirus disease 2019 pandemic.

J Hypertens 2021 06;39(6):1077-1089

Department of Hypertension, National Institute of Cardiology, Warsaw, Poland.

Summary: The coronavirus disease 2019 (COVID-19) pandemic considerably affects health, wellbeing, social, economic and other aspects of daily life. The impact of COVID-19 on blood pressure (BP) control and hypertension remains insufficiently explored. We therefore provide a comprehensive review of the potential changes in lifestyle factors and behaviours as well as environmental changes likely to influence BP control and cardiovascular risk during the pandemic. This includes the impact on physical activity, dietary patterns, alcohol consumption and the resulting consequences, for example increases in body weight. Other risk factors for increases in BP and cardiovascular risk such as smoking, emotional/psychologic stress, changes in sleep patterns and diurnal rhythms may also exhibit significant changes in addition to novel factors such as air pollution and environmental noise. We also highlight potential preventive measures to improve BP control because hypertension is the leading preventable risk factor for worldwide health during and beyond the COVID-19 pandemic.
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http://dx.doi.org/10.1097/HJH.0000000000002770DOI Listing
June 2021

PTGIR, a susceptibility gene for fibromuscular dysplasia?

Cardiovasc Res 2021 03;117(4):990-992

Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Belgium.

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http://dx.doi.org/10.1093/cvr/cvaa353DOI Listing
March 2021

Influence of secretory phenotype and preoperative preparation on surgical outcome in pheochromocytoma.

Endocr Connect 2021 Jan;10(1):92-101

Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

Objectives: Surgery of pheochromocytomas (PCs) still carries a high risk of haemodynamic complications during the perioperative period. We aimed to evaluate the influence of their secretory phenotype and preoperative alpha-blocker treatment on surgical outcome.

Design: A retrospective monocentric study at a tertiary medical centre.

Patients: In this study, 80 consecutive patients operated by the same team for a PC between 1988 and 2018.

Results: Diagnosis was based on typical symptoms and signs in 58 patients, genetic testing in 12 and work-up of an adrenal incidentaloma in 9. It was made during surgery in one patient. A genetic predisposition was found in one-third of index cases (21/62). The majority of the patients (73/79) had a secreting PC; more than 2/3 had an adrenergic phenotype and less than 1/3 a noradrenergic phenotype. The rate of perioperative haemodynamic complications was not influenced by the secretory phenotype, but persistent hypertension after surgery, recurrence and malignancy were more frequently observed in patients with a noradrenergic tumour. Preoperative alpha-blocker treatment was given for ≥ 14 days in 29 patients and, although being more symptomatic at diagnosis, these patients had less haemodynamic complications (3/29 vs 12/51 non-treated patients, P = 0.05).

Conclusions: The occurrence of haemodynamic complications during surgery was not significantly affected by the secretory phenotype in our study, but noradrenergic tumours show a worse post-surgical outcome. Our data also provide additional support in favour of a sufficient preoperative alpha-blockade in patients with pheochromocytoma.
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http://dx.doi.org/10.1530/EC-20-0537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923042PMC
January 2021

Increased Blood Pressure Variability May Herald Cognitive Decline and Dementia.

Hypertension 2020 10 9;76(4):1076-1078. Epub 2020 Sep 9.

Division of Cardiology, Cliniques Universitaires Saint-Luc Université catholique de Louvain, Brussels, Belgium (A.P.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14785DOI Listing
October 2020

Renal Denervation in Hypertensive Patients: Back to Anatomy?

Hypertension 2020 10 9;76(4):1084-1086. Epub 2020 Sep 9.

Department of Cardiovascular Medicine, Centre Hospitalier Princesse Grace, Monaco (A. Pathak).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480938PMC
October 2020
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