资源描述
Vol.72-No.?MiNerVa Cardiology aNd aNgiology1GUID ELI N ESitalian Society of interventional Cardiology(giSe)and italian Society of arterial Hypertension(Siia)Position Paper on the role of renal denervation in the management of the difficult-to-treat hypertensionEugenio STABILE 1,Maria l.MUieSaN 2,Flavio L.RIBICHINI 3,Giuseppe SANGIORGI 4,Stefano TADDEI 5,Francesco VerSaCi 6,Bruno VILLARI 7,Alessandra BACCA 5,Daniela BENEDETTO 4,Vincenzo FIORETTI 1,8,Eugenio LAURENZANO 7,Massimilano SCAPATICCI 6,Francesco Saia 9,Giuseppe TARANTINI 10,Guido GRASSI 11,Giovanni ESPOSITO 8*1Division of Cardiology,Cardiovascular Department,Azienda Ospedaliera Regionale“San Carlo”,Potenza,italy;2Department of Clinical and Experimental Sciences,University of Brescia,Brescia,Italy;3division of Cardiovascular Medicine,Department of Medicine,University of Verona,Verona,Italy;4division of Cardiology,Tor Vergata University Hospital,Rome,Italy;5department of Clinical and experimental Medicine,University of Pisa,Pisa,italy;6division of Cardiology,Santa Maria goretti Hospital,latina,italy;7division of Cardiology,Sacro Cuore di Ges Hospital,Benevento,Italy;8Division of Cardiology,Department of Advanced Biomedical Sciences,University of Naples Federico ii,Naples,italy;9Cardiology Unit,Cardio-Thoraco-Vascular Department,IRCCS University Hospital of Bologna,Policlinico S.Orsola,Bologna,Italy;10Department of Cardiac,Thoracic,Vascular Sciences and Public Health,University of Padua Medical School,Padua,Italy;11Clinica Medica,University of Milano-Bicocca,Milan,Italy*Corresponding author:Giovanni Esposito,Division of Cardiology,Department of Advanced Biomedical Sciences,University of Naples Federico II,Via Pansini 5,80123 Naples,Italy.E-mail:espogiovunina.itThis is an open access article distributed under the terms of the Creative Commons CC BY-NC license which allows users to distribute,remix,adapt and build upon the manuscript,as long as this is not done for commercial purposes,the user gives appropriate credits to the original author(s)and the source(with a link to the formal publication through the relevant DOI),provides a link to the license and indicates if changes were made.Full details on the CC BY-NC 4.0 are available at https:/creativecommons.org/licenses/by-nc/4.0/.ABS TRA C TRenal denervation(RDN)is a safe and effective strategy for the treatment of difficult to treat hypertension.The blood pressure(BP)-lowering efficacy of RDN is comparable to those of many single antihypertensive medications and it al-lows to consider the RDN as a valuable option for the treatment of difficult to treat hypertension together with lifestyle modifications and medical therapy.A multidisciplinary team is of pivotal importance from the selection of the patient candidate for the procedure to the post-procedural management.Further studies are needed to investigate the effect of RDN on clinical outcomes and to better identify the predictors of BP response to RDN in order to recognize the patients who are more likely to benefit from the procedure.(Cite this article as:Stabile E,Muiesan ML,Ribichini FL,Sangiorgi G,Taddei S,Versaci F,et al.italian Society of interven-tional Cardiology(giSe)and italian Society of arterial Hypertension(Siia)Position Paper on the role of renal denervation in the management of the difficult-to-treat hypertension.Minerva Cardiol Angiol 2024 Mar 27.DOI:10.23736/S2724-5683.23.06433-5)Key words:Denervation;Hypertension;Guideline.Minerva Cardiology and Angiology 2024 Mar 27 DOI:10.23736/S2724-5683.23.06433-5 2023 THE AUTHORSOpen access at https:/www.minervamedica.itSTABILE RENAL DENERVATION:FROM EVIDENCE TO PRACTICE2 MiNerVa Cardiology aNd aNgiology Mese 2024 The sympathetic nervous system plays a key role in the development of primary hypertension,and sympathetic activity is increased in many pa-tients with resistant hypertension.6 A crosstalk is present between the kidney and the central ner-vous system and involves both sensory afferent nerves and sympathetic efferent nerves(Figure 1).7 renal pathological processes increased af-ferent signalling nerves causing central sympa-thetic activation,that in turn through efferent nerves induces activation of the RAS,arteriolar vasoconstriction,increased heart rate(Hr)and myocardial contractility.All these effects ul-timately trigger BP elevation.6 Catheter-based renal denervation(RDN),ablating both afferent and efferent renal sympatethic nerves,modu-lates the overactive signaling between the kidney and central nervous system,and as consequence represents an additional option in the armamen-tarium for the treatment of arterial hypertension.8An unmet clinical needThe number of subjects aged 3079 years with hypertension doubled from 331 million women and 317 million men in 1990 to 626 million women and 652 million men in 2019,despite a stable age-standardized prevalence worldwide.Among them,the treatment rate was only 47%in women and 38%in men.Moreover,less than half of those treated,reached adequate control of arterial hypertension is the leading risk fac-tor for cardiovascular(CV)disease,and it is related to about two-thirds of all cerebrovascular accidents and half of all ischemic heart disease worldwide.It affects over one billion people worldwide and its global burden is rising due to escalating obesity and population aging.1Lifestyle modifications and drug therapy are the mainstays of treatment.2 Benefits of treatment are well established:a meta-analysis found that a 10 mmHg reduction in systolic blood pressure(SBP)reduced the risk of major CV events by 20%,cor-onary artery disease by 17%,stroke by 27%,heart failure by 28%and all-cause mortality by 13%.3However,despite the availability of many ef-fective and safe antihypertensive medications,globally only about one in five adults with hy-pertension have their blood pressure(BP)under control.4 A common form of uncontrolled hyper-tension is resistant hypertension,which is de-fined as uncontrolled BP despite the use of 3 an-tihypertensive agents with different mechanisms of action,including a diuretic,usually thiazide-like,a long-acting calcium channel blocker,and a blocker of the renin-angiotensin system(RAS),at maximal or maximally tolerated doses.The diagnosis of resistant hypertension requires the exclusion of several possible causes of pseudo-resistant hypertension,including poor adherence to prescribed drugs,white coat-hypertension,clinical inertia and inaccurate BP measurement.5Figure 1.Brain-kidney sympathetic crosstalk.Sche-matic representation of sym-pathetic tone crosstalk with afferent signaling from the kidney to the central nervous system and efferent signal-ling from the central nervous system to the kidney.Affer-ent signalling is triggered by different types of renal inju-ry.Efferent signalling causes arterial hypertension acting through the kidney and the cardiovascular system.SNS:sympathetic nervous system;RAAS:renin angio-tensin aldosterone system.Renal injuryRenal ischemiaCentral SNS integration-Reduced renal blood flow-Activation of the RAAS-Sodium retention-Vasoconstriction-Increased HR-Increased cardiac contractilityRENAL DENERVATION:FROM EVIDENCE TO PRACTICE STABILEVol.72-No.?MiNerVa Cardiology aNd aNgiology 3that predictors of preference for rdN on lo-gistic regression analysis were younger patient age,male sex,higher home or office SBP,poor antihypertensive drug adherence,the presence of heart failure and the presence of side effects during treatment with antihypertensive drugs.15 Moreover,the majority of patients included in the questionnaire-based cross-sectional survey in Germany,reported that doctors were most likely to be their main source of information regarding medical problems and to influence their decision regarding medical therapies.14 on the other hand,many clinicians accept unmet BP goals without taking decisive steps and changing therapeutic regimens,even in patients at moderate or high CV risk.16,17 In the USA a national survey of ambulatory care conducted from 2005 to 2012,revealed that among adults with uncontrolled hypertension,only one out of six patients expe-rienced an intensification of their drug regimen by their primary care physician.18 These results underline the need for a structured process,in-cluding patients preferences and perspectives,in order to select the ideal therapeutic strategy for hypertensive patients.To offset these difficulties observed in the real world of hypertensive patients,new non-phar-macological,device-based therapeutic approach-es have been developed.The potential applica-tion of RDN in clinical practice has been tested in clinical trials,showing a BP-lowering efficacy both in patients with and without concomitant antihypertensive medication.Therefore,recent consensus documents from the European Soci-ety of Hypertension,the italian Society of Hy-pertension,the Society for Cardiovascular Angi-ography and Interventions(SCAI),ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions(eaPCi)have considered rdN as an innovative third option in the armamentarium of antihyper-tensive treatment after lifestyle modification and medical therapy.19-22 The European Society of Hypertension(ESH)guidelines for the manage-ment of arterial hypertension considered rdN as a treatment option in patients with an esti-mated glomerular filtration rate(eGFR)40 ml/min/1.73m2 who have uncontrolled BP despite the use of antihypertensive drug combination BP values,with global control rates of 23%and 18%respectively for women and men.4 despite improvements in the diagnosis and treatment of hypertension,especially in middle and high-in-come countries,the prevalence of controlled BP still remains unsatisfactory.4 The prevalence of controlled BP in the USA increased to 53.8%in 2013-2014 and then declined to 43.7%in 2017-2018,despite accepting a target control systolic BP value of 140 mmHg.9 Failure to achieve goal BP was also observed in Italy,where over one decade of observation(from 2000 to 2011)only 33%of hypertensive patients achieved effective BP control.10Non-adherence to pharmacological treatment remains one of the most important causes of un-controlled hypertension.11,12 a large prospective italian study including more than 240.000 pa-tients newly treated with antihypertensive drugs,investigated the incidence of cardiovascular events according to drug coverage,tracked by prescription registries.CV risk reductions of 20 and 25%were reported respectively in patients with intermediate(proportion of days covered from 51%to 75%)and high drug coverage(pro-portion of days covered 75%)as compared with patients with very low drug coverage(proportion of days covered 25%).13Non-adherence to pharmacological treatment is a multifactorial phenomenon.Five categories of factors impacting adherence to prescribed medications have been identified:social and eco-nomic(age,education and socioeconomic sta-tus),healthcare system-related(patient-physician relationship,access to and cost of care),therapy-related(complex regimens,treatment changes,duration and adverse effects),condition-related(multiple comorbidities,symptom severity and quality of life)and patient-related(fear of de-pendence or adverse effects,lack of knowledge,denied diagnosis and forgetfullness).11,12A questionnaire-based cross-sectional survey was performed in about one thousand patients with elevated BP in Germany;almost 40%of those patients not on medication and almost 30%of those on drug therapy,were prone to choose one-time catheter-based RDN in the treatment of hypertension.14 Similar results were observed in a survey conducted in Japan,which revealed STABILE RENAL DENERVATION:FROM EVIDENCE TO PRACTICE4 MiNerVa Cardiology aNd aNgiology Mese 2024 concomitant medications,study populations and procedural aspects have been adopted accord-ing with the third European Clinical Consensus Conference for clinical trials in device-based hypertension therapies.26 Since then,five sham-controlled randomized trials showed safety and efficacy of second generation radio frequency(RF)or ultrasound(US)systems in patients with or without concomitant medical therapy.27-31 The reduction in office SBP ranged from-9.0 to-10.8 mmHg and in the diastolic blood pressure(DBP)from-5.0 to-5.5 mmHg,whereas the decrease in ambulatory BP ranges from-4.7 to-9.0 mmHg for SBP and-3.7 to-6.0 mmHg for DBP(Fig-ure 2).19 More recently also the radiaNCe ii trial demonstrated a significant reduction in day-time ambulatory SBP at 2 months with US-based rdN(mean-7.9 mmHg)vs.the sham procedure(mean-1.8 mmHg)in the absence of antihyper-tensive medications.32 A subgroup analysis of the Global SYMPLICITY Registry DEFINE showed that BP reduction after RDN was independent of the number and type of baseline antihypertensive therapy,or if drug treatment elicits serious side effects and poor quality of life(class of recom-mendation CoR II,level of evidence LoE B).Moreover,its recommended that RDN should only be performed in experienced specialized centers to guarantee appropriate selection of eli-gible patients and completeness of the denerva-tion procedure(CoR I,LoE C).23Available data of clinical efficacy and safetyThe SYMPLICITY HTN-3 trial failed to show a significant reduction of SBP in patients with re-sistant hypertension 6 months after rdN as com-pared with a sham control,despite a reduction in SBP of 14.1 mmHg.24 The possible reasons for the failure are multifactorial and include frequent medication changes during the study period,use of first generation device,incomplete denerva-tion,lack of experience of many operators,pro-cedure variability and inadequate follow up dura-tion.25 after this trial,several changes in terms of Figure 2.Effect of RDN on BP control:A)Barr graph representing change in 24-h ambulatory blood pressure after renal de-nervation observed in sham-controlled randomized clinical trials of second generation;B)Barr graph representing the change in office blood pressure after RDN observed in the sham-controlled randomized clinical trial of second generation.Data are shown as mean BP change from baseline to the time point of each study primary objective.P values are given for difference between treatment and sham group adjusted for mean baseline BP.aBABPM SBPABPM DBPOffice SBPOffice DBPRadiance HTN TrioSpyral HTN ON-medSpyral HTN OFF-med PivotalRadiance HTN SoloSpyral HTN-OFF med-10-9-8-7-6-5-4-3-2-1 0ShamRDNRadiance HTN TrioSpyral HTN ON-medSpyral HTN OFF-med PivotalRadiance HTN SoloSpyral HTN-OFF med-12-10-8-6-4-2 0ShamRDNP=0.04P=0.03P0.001P=0.007P=0.02ShamRDN-6-5-4-3-2-1 0Radiance HTN TrioSpyral HTN ON-medSpyral HTN OFF-med PivotalRadiance HTN SoloSpyral HTN-OFF medP=0.16P0.001P=0.02P=0.005P=0.08Radiance HTN TrioSpyral HTN ON-medSpyral HTN OFF-med PivotalRadiance HTN SoloSpyral HTN-OFF medP=0.04P=0.02P=0.006P0.001P=0.006P=0.003P=0.02P=0.12P0.001P=0.07-7-6-5-4-3-2-1 0ShamRDNRENAL DENERVATION:FROM EVIDENCE TO PRACTICE STABILEVol.72
展开阅读全文
浙ICP备2021020529号-1 | 浙B2-20240490 
