|
1
|
Lipphardt M, Koziolek MJ, Lehnig LY, Schäfer AK, Müller GA, Lüders S, Wallbach M. Effect of baroreflex activation therapy on renal sodium excretion in patients with resistant hypertension. Clin Res Cardiol 2019; 108:1287-1296. [DOI: 10.1007/s00392-019-01464-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2019] [Accepted: 03/19/2019] [Indexed: 12/29/2022]
|
|
2
|
Tsioufis C, Ziakas A, Dimitriadis K, Davlouros P, Marketou M, Kasiakogias A, Thomopoulos C, Petroglou D, Tsiachris D, Doumas M, Skalidis E, Karvounis C, Alexopoulos D, Vardas P, Kallikazaros I, Stefanadis C, Papademetriou V, Tousoulis D. Blood pressure response to catheter-based renal sympathetic denervation in severe resistant hypertension: data from the Greek Renal Denervation Registry. Clin Res Cardiol 2017; 106:322-330. [PMID: 27957627 DOI: 10.1007/s00392-016-1056-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Accepted: 11/22/2016] [Indexed: 12/28/2022]
Abstract
BACKGROUND/INTRODUCTION The efficacy of catheter-based renal sympathetic denervation (RDN) in terms of blood pressure (BP) reduction has been questioned, while "real-world" data from registries are needed. In this study, we report the complete set of 12-month data on office and ambulatory BP changes as well as the predictors for BP response to RDN from a national registry. METHODS In 4 Greek hospital centers, 79 patients with severe drug-resistant hypertension (age 59 ± 10 years, 53 males, body mass index 33 ± 5 kg/m2; office BP and 24-h ambulatory BP were 176 ± 15/95 ± 13 and 155 ± 14/90 ± 12 mmHg, respectively, 4.4 ± 0.9 antihypertensive drugs) underwent RDN and were followed-up for 12 months in the Greek Renal Denervation Registry. Bilateral RDN was performed using percutaneous femoral approach and standardized techniques. RESULTS Reduction in office systolic/diastolic BP at 6 and 12 months from baseline was -30/-12 and -29/-12 mmHg, while the reduction in 24-h ambulatory BP was -16/-9 and -15/-9 mmHg, respectively (p < 0.05 for all). Patients that were RDN responders (85%, n = 58), defined as an at least 10-mmHg decrease in office systolic BP at 12 months, compared to non-responders were younger (57 ± 9 vs 65 ± 8 years, p < 0.05), had higher baseline office systolic BP (176 ± 17 vs 160 ± 11 mmHg, p < 0.05) and 24-h systolic BP (159 ± 13 vs 149 ± 11 mmHg, p < 0.05). Stepwise logistic regression analysis revealed that age, obesity parameters, and baseline office BP were independent predictors of RDN response (p < 0.05 for both), but not the type of RDN catheter or the use of aldosterone antagonists. At 12 months, there were no significant changes in renal function and any new serious device or procedure-related adverse events. CONCLUSIONS In our "real-world" multicenter national registry, the efficacy of renal denervation in reducing BP as well as safety is confirmed during a 12-month follow-up. Moreover, younger age, obesity, and higher levels of baseline systolic BP are independently related to better BP response to RDN.
Collapse
Affiliation(s)
- C Tsioufis
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece.
| | - A Ziakas
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - K Dimitriadis
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece
| | - P Davlouros
- Department of Cardiology, Patras University Hospital, Patras, Greece
| | - M Marketou
- Cardiology Department, Heraklion University Hospital, Crete, Greece
| | - A Kasiakogias
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece
| | - C Thomopoulos
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece
| | - D Petroglou
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - D Tsiachris
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece
| | - M Doumas
- 2nd Propedeutic Department of Internal Medicine, Aristotle University, Thessaloniki, Greece
| | - E Skalidis
- Cardiology Department, Heraklion University Hospital, Crete, Greece
| | - C Karvounis
- First Department of Cardiology, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - D Alexopoulos
- Department of Cardiology, Attikon University Hospital, Athens, Greece
| | - P Vardas
- Cardiology Department, Heraklion University Hospital, Crete, Greece
| | - I Kallikazaros
- Cardiology Department, Hippokration Hospital, Athens, Greece
| | - C Stefanadis
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece
| | - V Papademetriou
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece
| | - D Tousoulis
- First Cardiology Clinic, Hippokration Hospital, University of Athens, 114 Vas.Sofias Ave., 11527, Athens, Greece
| |
Collapse
|
|
3
|
Imprialos KP, Boutari C, Stavropoulos K, Doumas M, Karagiannis AI. Stroke paradox with SGLT-2 inhibitors: a play of chance or a viscosity-mediated reality? J Neurol Neurosurg Psychiatry 2017; 88:249-253. [PMID: 27895093 DOI: 10.1136/jnnp-2016-314704] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2016] [Accepted: 11/09/2016] [Indexed: 02/06/2023]
Abstract
Diabetes mellitus is a major risk factor for cardiovascular morbidity and mortality. Current therapeutic strategies have not provided constant beneficial cardiovascular-related results. Sodium-glucose co-transporters 2 (SGLT-2) inhibitors have emerged as a novel antidiabetic class of drugs that exert favourable results in a variety of other cardiovascular risk factors too, such as increased blood pressure and body weight. The Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) study was the first trial that evaluated cardiovascular outcomes in patients with diabetes with the use of empagliflozin, a member of this new class of drugs. Empagliflozin was associated with remarkable reduction of cardiovascular morbidity and mortality and all-cause death. On the contrary, stroke incidence was slightly increased, although the result did not reach statistical significance. It could be assumed that a drug providing such beneficial effects on cardiovascular outcomes, would have also the same impact in stroke risk. This finding could theoretically be attributed to 'play of chance'. However, an increase of haematocrit was observed in EMPA-REG and other SGLT-2 inhibitors studies. Accumulating evidence suggests a direct association between increased haematocrit and stroke risk. Could this 'stroke paradox' be a result of the increased haematocrit levels noted with SGLT-2 inhibitors? The aim of this review is to critically assess both possibilities, given that increased stroke rates (if indeed true) should not be neglected and unattended.
Collapse
Affiliation(s)
- Konstantinos P Imprialos
- Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Chrysoula Boutari
- Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Konstantinos Stavropoulos
- Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | | | - Asterios I Karagiannis
- Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| |
Collapse
|
|
4
|
Cardoso CRL, Salles GF. Prognostic Importance of Ambulatory Blood Pressure Monitoring in Resistant Hypertension: Is It All that Matters? Curr Hypertens Rep 2016; 18:85. [PMID: 27837396 DOI: 10.1007/s11906-016-0693-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW This article reviews the current knowledge on the prognostic importance of ambulatory blood pressure (BP) monitoring parameters in patients with apparent treatment-resistant hypertension. RECENT FINDINGS Although mean 24-h ambulatory BPs have been consistently established as better cardiovascular risk predictors than clinic (office) BPs in several clinical settings, and ambulatory BP monitoring is generally indicated in patients with resistant hypertension; there were only five previous longitudinal prospective studies that specifically evaluated the prognostic importance of ambulatory BP monitoring parameters in resistant hypertensive patients. These studies are carefully reviewed here. In conjunction, they demonstrated that office BP levels have little, if any, prognostic value in resistant hypertensive patients. Otherwise, several ambulatory BP monitoring parameters are strong cardiovascular risk predictors, particularly nighttime sleep BPs and the non-dipping pattern. Most relevant, the ambulatory BP monitoring diagnosis of true resistant hypertension (i.e., patients with uncontrolled ambulatory BPs, either daytime or nighttime) doubled the risk of future occurrence of major cardiovascular events in contrast to patients with white-coat resistant hypertension (i.e., with controlled ambulatory BPs despite uncontrolled office BPs). This review reinforces the pivotal role of serial ambulatory BP monitoring examinations in the clinical management of patients with resistant hypertension.
Collapse
Affiliation(s)
- Claudia R L Cardoso
- Department of Internal Medicine, School of Medicine and University Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Croton, 72, Jacarepaguá, Rio de Janeiro, RJ, CEP: 22750-240, Brazil
| | - Gil F Salles
- Department of Internal Medicine, School of Medicine and University Hospital Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Croton, 72, Jacarepaguá, Rio de Janeiro, RJ, CEP: 22750-240, Brazil.
| |
Collapse
|
|
5
|
Lambert T, Nahler A, Rohla M, Reiter C, Grund M, Kammler J, Blessberger H, Kypta A, Kellermair J, Schwarz S, Starnawski JA, Lichtenauer M, Weiss TW, Huber K, Steinwender C. Endpoint design for future renal denervation trials - Novel implications for a new definition of treatment response to renal denervation. Int J Cardiol 2016; 220:273-8. [PMID: 27390940 DOI: 10.1016/j.ijcard.2016.06.110] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Revised: 06/12/2016] [Accepted: 06/21/2016] [Indexed: 10/21/2022]
Abstract
BACKGROUND Defining an adequate endpoint for renal denervation trials represents a major challenge. A high inter-individual and intra-individual variability of blood pressure levels as well as a partial or total non-adherence on antihypertensive drugs hamper treatment evaluations after renal denervation. Blood pressure measurements at a single point in time as used as primary endpoint in most clinical trials on renal denervation, might not be sufficient to discriminate between patients who do or do not respond to renal denervation. METHODS We compared the traditional responder classification (defined as systolic 24-hour blood pressure reduction of -5mmHg six months after renal denervation) with a novel definition of an ideal respondership (based on a 24h blood pressure reduction at no point in time, one, or all follow-up timepoints). RESULTS We were able to re-classify almost a quarter of patients. Blood pressure variability was substantial in patients traditionally defined as responders. On the other hand, our novel classification of an ideal respondership seems to be clinically superior in discriminating sustained from pseudo-response to renal denervation. CONCLUSION Based on our observations, we recommend that the traditional response classification should be reconsidered and possibly strengthened by using a composite endpoint of 24h-BP reductions at different follow-up-visits.
Collapse
Affiliation(s)
- Thomas Lambert
- Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria.
| | - Alexander Nahler
- Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria
| | - Miklos Rohla
- 3rd Medical Department - Cardiology and Intensive Care Medicine, Wilhelminenhospital Vienna, Austria
| | - Christian Reiter
- Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria
| | - Michael Grund
- Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria
| | - Jürgen Kammler
- Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria
| | - Hermann Blessberger
- Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria
| | - Alexander Kypta
- Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria
| | - Jörg Kellermair
- Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria
| | - Stefan Schwarz
- Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria
| | - Jennifer A Starnawski
- Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria
| | - Michael Lichtenauer
- Clinic of Internal Medicine II - Department of Cardiology, Paracelsus Medical University of Salzburg, Austria
| | - Thomas W Weiss
- 3rd Medical Department - Cardiology and Intensive Care Medicine, Wilhelminenhospital Vienna, Austria
| | - Kurt Huber
- 3rd Medical Department - Cardiology and Intensive Care Medicine, Wilhelminenhospital Vienna, Austria
| | - Clemens Steinwender
- Department of Cardiology, Kepler University Hospital Linz, Johannes Kepler University Linz, Austria
| |
Collapse
|
|
6
|
Li P, Nader M, Arunagiri K, Papademetriou V. Device-Based Therapy for Drug-Resistant Hypertension: An Update. Curr Hypertens Rep 2016; 18:64. [PMID: 27402013 DOI: 10.1007/s11906-016-0671-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Drug-resistant hypertension (RH) remains a significant and common cardiovascular risk despite the availability of multiple potent antihypertensive medications. Uncontrolled resistant hypertension contributes substantially to excessive cardiovascular and renal morbidity and mortality. Clinical and experimental evidence suggest that sympathetic nervous system over-activity is the main culprit for the development and maintenance of drug-resistant hypertension. Both medical and interventional strategies, targeting the sympathetic over-activation, have been designed in patients with hypertension over the past few decades. Minimally invasive, catheter-based, renal sympathetic denervation (RDN) and carotid baroreceptor activation therapy (BAT) have been extensively evaluated in patients with RH in clinical trials. Current trial outcomes, though at times impressive, have been mostly uncontrolled trials in need of validation. Device-based therapy for drug-resistant hypertension has the potential to provide alternative treatment options to certain groups of patients who are refractory or intolerant to current antihypertensive medications. However, more research is needed to prove its efficacy in both animal models and in humans. In this article, we will review the evidence from recent renal denervation, carotid baroreceptor stimulation therapy, and newly emerged central arteriovenous anastomosis trials to pinpoint the weak links, and speculate on potential alternative approaches.
Collapse
Affiliation(s)
- Ping Li
- Washington Veterans Affairs Medical Center, 50 Irving Street, N.W., Washington, DC, 20422, USA
- Georgetown University Hospital, Washington, DC, USA
- George Washington University Hospital, Washington, DC, USA
| | - Mark Nader
- Georgetown University Hospital, Washington, DC, USA
| | | | - Vasilios Papademetriou
- Washington Veterans Affairs Medical Center, 50 Irving Street, N.W., Washington, DC, 20422, USA.
- Georgetown University Hospital, Washington, DC, USA.
| |
Collapse
|
|
7
|
Papademetriou V, Doumas M, Tsioufis C. Renal Sympathetic Denervation: Hibernation or Resurrection? Cardiology 2016; 135:87-97. [DOI: 10.1159/000446909] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Accepted: 05/12/2016] [Indexed: 11/19/2022]
Abstract
The most current versions of renal sympathetic denervation have been invented as minimally invasive approaches for the management of drug-resistant hypertension. The anatomy, physiology and pathophysiology of renal sympathetic innervation provide a strong background supporting an important role of the renal nerves in the regulation of blood pressure (BP) and volume. In addition, historical data with surgical sympathectomy and experimental data with surgical renal denervation indicate a beneficial effect on BP levels. Early clinical studies with transcatheter radiofrequency ablation demonstrated impressive BP reduction, accompanied by beneficial effects in target organ damage and other disease conditions characterized by sympathetic overactivity. However, the failure of the SYMPLICITY 3 trial to meet its primary efficacy end point raised a lot of concerns and put the field of renal denervation into hibernation. This review aims to translate basic research into clinical practice by presenting the anatomical and physiological basis for renal sympathetic denervation, critically discussing the past and present knowledge in this field, where we stand now, and also speculating about the future of the intervention and potential directions for research.
Collapse
|
|
8
|
Schwerg M, Eilers B, Wienecke A, Baumann G, Laule M, Knebel F, Stangl K, Stangl V. Galectin-3 and prediction of therapeutic response to renal sympathetic denervation. Clin Exp Hypertens 2016; 38:399-403. [PMID: 27159890 DOI: 10.3109/10641963.2016.1148157] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The profibrotic mediator Galectin-3 (Gal-3) has been associated with aldosterone-mediated vascular inflammation, fibrosis, and stiffness. We evaluated whether the Gal-3 levels and change in Gal-3 as associated with renal denervation can serve as prediction of therapeutic response to renal denervation. A total of 42 patients with resistant hypertension undergoing renal sympathetic denervation (RDN) were included. Blood pressure was evaluated by 24-h ambulatory measurement before RDN and 1, 3 and 6 months after RDN. Treatment response was defined as a drop in systolic ambulatory blood pressure of >5 mm Hg after 6 months. Blood samples were assessed for Gal-3 levels. For the entire group, a significant drop in mean systolic ambulatory blood pressure of 5.2 ± 18.6 mm Hg was observed (p = 0.032). The responder rate was 50% (n = 21). At baseline, Gal-3 levels were significantly higher in responders (14.5 ± 6.0 vs. 10.95 ± 4.6 ng/ml, p = 0.017). There were no significant changes of Gal-3 levels during the follow-up period. The profibrotic biomarker may help to identify patients suitable for RDN.
Collapse
Affiliation(s)
- Marius Schwerg
- a Department of Cardiology and Angiology , Campus Mitte, Charité - Universitätsmedizin , Berlin , Germany
| | - Björn Eilers
- b Labor Berlin, Charite Vivantes Service GmbH , Berlin , Germany
| | - Anja Wienecke
- a Department of Cardiology and Angiology , Campus Mitte, Charité - Universitätsmedizin , Berlin , Germany
| | - Gert Baumann
- a Department of Cardiology and Angiology , Campus Mitte, Charité - Universitätsmedizin , Berlin , Germany
| | - Michael Laule
- a Department of Cardiology and Angiology , Campus Mitte, Charité - Universitätsmedizin , Berlin , Germany
| | - Fabian Knebel
- a Department of Cardiology and Angiology , Campus Mitte, Charité - Universitätsmedizin , Berlin , Germany
| | - Karl Stangl
- a Department of Cardiology and Angiology , Campus Mitte, Charité - Universitätsmedizin , Berlin , Germany
| | - Verena Stangl
- a Department of Cardiology and Angiology , Campus Mitte, Charité - Universitätsmedizin , Berlin , Germany
| |
Collapse
|
|
9
|
Turner JR, Durham TA. Meta-methodology: conducting and reporting meta-analyses. J Clin Hypertens (Greenwich) 2015; 16:91-3. [PMID: 24734310 DOI: 10.1111/jch.12215] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
|
|
10
|
Hameed MA, Pucci M, Martin U, Watkin R, Doshi S, Freedman J, Riley P, Townend J, Crowe P, Lipkin G, Dasgupta I. Renal Denervation in Patients With Uncontrolled Hypertension and Confirmed Adherence to Antihypertensive Medications. J Clin Hypertens (Greenwich) 2015; 18:565-71. [PMID: 26434739 DOI: 10.1111/jch.12713] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 07/10/2015] [Accepted: 07/12/2015] [Indexed: 11/28/2022]
Abstract
Renal denervation (RDN) has emerged as a potential device-based treatment for resistant hypertension. The authors present their experience of the use of catheter-based RDN as part of routine clinical care in two specialist hypertension clinics. Thirty-four patients with uncontrolled hypertension underwent RDN. All patients had ambulatory blood pressure (BP) monitoring and directly observed medication administration prior to the procedure to exclude white-coat hypertension and nonadherence, respectively. Overall, there was a significant change in clinic systolic BP of -15.1 mm Hg (95% confidence interval, -23.4 to -6.8; P=.001) and clinic diastolic BP of -6.2 mm Hg (95% confidence interval, -11.5 to -0.9; P=.02) 6 months postprocedure, and a nonsignificant change in daytime ambulatory BP of -5.4/-2.9 mm Hg. Eighteen patients (51.4%) showed a significant reduction in their clinic systolic BP (≥10 mm Hg) and 16 (47%) had a significant reduction in their daytime ambulatory systolic BP (≥5 mm Hg) at 6 months.
Collapse
Affiliation(s)
| | - Mark Pucci
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Una Martin
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.,College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
| | | | - Sagar Doshi
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | | | - Peter Riley
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Jonathan Townend
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Paul Crowe
- Heart of England NHS Foundation Trust, Birmingham, UK
| | - Graham Lipkin
- University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | | |
Collapse
|
|
11
|
Prkacin I, Balenovic D, Djermanovic-Dobrota V, Lukac I, Drazic P, Pranjic IK. Resistant hypertension and chronotherapy. Mater Sociomed 2015; 27:118-21. [PMID: 26005390 PMCID: PMC4404987 DOI: 10.5455/msm.2015.27.118-121] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2015] [Accepted: 04/05/2015] [Indexed: 12/02/2022] Open
Abstract
Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg in spite of the continuous use of three antihypertensive agents in optimal dose, including diuretic, and lifestyle changes. According to data from United States of America and Europe, the prevalence ranges from 10 up to 30% in patients with hypertension. Numerous biological and lifestyle factors can contribute to the development of resistant hypertension: medications, volume overload, obesity, diabetes mellitus, older age, renal parenchymal and renovascular disease, primary aldosteronism, obstructive sleep apnea, pheochormocytoma, Cushing’s syndrome, thyroid diseases, aortic coarctation. For diagnosing patient’s history is important, assessing compliance, regular blood pressure measurement, physical examination, biochemical evaluation and noninvasive imaging. The evaluation including 24h ambulatory monitoring of blood pressure (ABPM) in the identification of “non-dipper” hypertension. Non-dipper has particular importance and the prevalence of abnormally high sleep blood pressure is very often in chronic kidney patients. Therapeutic restoration of normal physiologic blood pressure reduction during night-time sleep (circadial variation) is the most significant independent predictor of decreased risk and the basis for the chronotherapy. The resistant hypertension treatment is achieved with nonpharmacological and pharmacological approach, treating secondary hypertension causes and invasive procedures.
Collapse
Affiliation(s)
- Ingrid Prkacin
- Merkur University Hospital, Department of Internal Medicine, University of Zagreb, School of Medicine, Zagreb, Croatia
| | - Diana Balenovic
- General Hospital Sisak, Department of Internal Medicine, Sisak, Croatia
| | - Vesna Djermanovic-Dobrota
- Merkur University Hospital, Department of Internal Medicine, University of Zagreb, School of Medicine, Zagreb, Croatia
| | - Iva Lukac
- Merkur University Hospital, Department of Internal Medicine, University of Zagreb, School of Medicine, Zagreb, Croatia
| | - Petra Drazic
- Merkur University Hospital, Department of Internal Medicine, University of Zagreb, School of Medicine, Zagreb, Croatia
| | - Iva-Klara Pranjic
- General Hospital Zadar, Department of Emergency Medicine, Zadar, Croatia
| |
Collapse
|
|
12
|
|
|
13
|
Abstract
After three years of excessive confidence, overoptimistic expectations and performance of 15 to 20,000 renal denervation procedures in Europe, the failure of a single well-designed US trial—Symplicity HTN-3—to meet its primary efficacy endpoint has cast doubt on renal denervation as a whole. The use of a sound methodology, including randomisation and blinded endpoint assessment was enough to see the typical 25–30 mmHg systolic blood pressure decrease observed after renal denervation melt down to less than 3 mmHg, the rest being likely explained by Hawthorne and placebo effects, attenuation of white coat effect, regression to the mean and other physician and patient-related biases. The modest blood pressure benefit directly assignable to renal denervation should be balanced with unresolved safety issues, such as potentially increased risk of renal artery stenosis after the procedure (more than ten cases reported up to now, most of them in 2014), unclear long-term impact on renal function and lack of morbidity–mortality data. Accordingly, there is no doubt that renal denervation is not ready for clinical use. Still, renal denervation is supported by a strong rationale and is occasionally followed by major blood pressure responses in at-risk patients who may otherwise have remained uncontrolled. Upcoming research programmes should focus on identification of those few patients with truly resistant hypertension who may derive a substantial benefit from the technique, within the context of well-designed randomised trials and independent registries. While electrical stimulation of baroreceptors and other interventional treatments of hypertension are already “knocking at the door”, the premature and uncontrolled dissemination of renal denervation should remain an example of what should not be done, and trigger radical changes in evaluation processes of new devices by national and European health authorities.
Collapse
|
|
14
|
Zannad F, Stough WG, Mahfoud F, Bakris GL, Kjeldsen SE, Kieval RS, Haller H, Yared N, De Ferrari GM, Piña IL, Stein K, Azizi M. Design Considerations for Clinical Trials of Autonomic Modulation Therapies Targeting Hypertension and Heart Failure. Hypertension 2015; 65:5-15. [DOI: 10.1161/hypertensionaha.114.04057] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Faiez Zannad
- From the Department of Cardiology, INSERM, Center d’Investigation Clinique 9501 and Unité 961, Center Hospitalier Universitaire, Nancy University, Université de Lorraine, Nancy, France (F.Z.); Departments of Pharmacy Practice and Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC (W.G.S.); Klinik für Innere Medizin III, Universtitätsklinikum des Saarlandes, Homburg/Saar, Germany (F.M.); Harvard-MIT Biomedical Engineering, Institute of Medical Engineering
| | - Wendy Gattis Stough
- From the Department of Cardiology, INSERM, Center d’Investigation Clinique 9501 and Unité 961, Center Hospitalier Universitaire, Nancy University, Université de Lorraine, Nancy, France (F.Z.); Departments of Pharmacy Practice and Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC (W.G.S.); Klinik für Innere Medizin III, Universtitätsklinikum des Saarlandes, Homburg/Saar, Germany (F.M.); Harvard-MIT Biomedical Engineering, Institute of Medical Engineering
| | - Felix Mahfoud
- From the Department of Cardiology, INSERM, Center d’Investigation Clinique 9501 and Unité 961, Center Hospitalier Universitaire, Nancy University, Université de Lorraine, Nancy, France (F.Z.); Departments of Pharmacy Practice and Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC (W.G.S.); Klinik für Innere Medizin III, Universtitätsklinikum des Saarlandes, Homburg/Saar, Germany (F.M.); Harvard-MIT Biomedical Engineering, Institute of Medical Engineering
| | - George L. Bakris
- From the Department of Cardiology, INSERM, Center d’Investigation Clinique 9501 and Unité 961, Center Hospitalier Universitaire, Nancy University, Université de Lorraine, Nancy, France (F.Z.); Departments of Pharmacy Practice and Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC (W.G.S.); Klinik für Innere Medizin III, Universtitätsklinikum des Saarlandes, Homburg/Saar, Germany (F.M.); Harvard-MIT Biomedical Engineering, Institute of Medical Engineering
| | - Sverre E. Kjeldsen
- From the Department of Cardiology, INSERM, Center d’Investigation Clinique 9501 and Unité 961, Center Hospitalier Universitaire, Nancy University, Université de Lorraine, Nancy, France (F.Z.); Departments of Pharmacy Practice and Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC (W.G.S.); Klinik für Innere Medizin III, Universtitätsklinikum des Saarlandes, Homburg/Saar, Germany (F.M.); Harvard-MIT Biomedical Engineering, Institute of Medical Engineering
| | - Robert S. Kieval
- From the Department of Cardiology, INSERM, Center d’Investigation Clinique 9501 and Unité 961, Center Hospitalier Universitaire, Nancy University, Université de Lorraine, Nancy, France (F.Z.); Departments of Pharmacy Practice and Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC (W.G.S.); Klinik für Innere Medizin III, Universtitätsklinikum des Saarlandes, Homburg/Saar, Germany (F.M.); Harvard-MIT Biomedical Engineering, Institute of Medical Engineering
| | - Hermann Haller
- From the Department of Cardiology, INSERM, Center d’Investigation Clinique 9501 and Unité 961, Center Hospitalier Universitaire, Nancy University, Université de Lorraine, Nancy, France (F.Z.); Departments of Pharmacy Practice and Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC (W.G.S.); Klinik für Innere Medizin III, Universtitätsklinikum des Saarlandes, Homburg/Saar, Germany (F.M.); Harvard-MIT Biomedical Engineering, Institute of Medical Engineering
| | - Nadim Yared
- From the Department of Cardiology, INSERM, Center d’Investigation Clinique 9501 and Unité 961, Center Hospitalier Universitaire, Nancy University, Université de Lorraine, Nancy, France (F.Z.); Departments of Pharmacy Practice and Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC (W.G.S.); Klinik für Innere Medizin III, Universtitätsklinikum des Saarlandes, Homburg/Saar, Germany (F.M.); Harvard-MIT Biomedical Engineering, Institute of Medical Engineering
| | - Gaetano M. De Ferrari
- From the Department of Cardiology, INSERM, Center d’Investigation Clinique 9501 and Unité 961, Center Hospitalier Universitaire, Nancy University, Université de Lorraine, Nancy, France (F.Z.); Departments of Pharmacy Practice and Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC (W.G.S.); Klinik für Innere Medizin III, Universtitätsklinikum des Saarlandes, Homburg/Saar, Germany (F.M.); Harvard-MIT Biomedical Engineering, Institute of Medical Engineering
| | - Ileana L. Piña
- From the Department of Cardiology, INSERM, Center d’Investigation Clinique 9501 and Unité 961, Center Hospitalier Universitaire, Nancy University, Université de Lorraine, Nancy, France (F.Z.); Departments of Pharmacy Practice and Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC (W.G.S.); Klinik für Innere Medizin III, Universtitätsklinikum des Saarlandes, Homburg/Saar, Germany (F.M.); Harvard-MIT Biomedical Engineering, Institute of Medical Engineering
| | - Kenneth Stein
- From the Department of Cardiology, INSERM, Center d’Investigation Clinique 9501 and Unité 961, Center Hospitalier Universitaire, Nancy University, Université de Lorraine, Nancy, France (F.Z.); Departments of Pharmacy Practice and Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC (W.G.S.); Klinik für Innere Medizin III, Universtitätsklinikum des Saarlandes, Homburg/Saar, Germany (F.M.); Harvard-MIT Biomedical Engineering, Institute of Medical Engineering
| | - Michel Azizi
- From the Department of Cardiology, INSERM, Center d’Investigation Clinique 9501 and Unité 961, Center Hospitalier Universitaire, Nancy University, Université de Lorraine, Nancy, France (F.Z.); Departments of Pharmacy Practice and Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC (W.G.S.); Klinik für Innere Medizin III, Universtitätsklinikum des Saarlandes, Homburg/Saar, Germany (F.M.); Harvard-MIT Biomedical Engineering, Institute of Medical Engineering
| |
Collapse
|
|
15
|
Bausback Y, Friedenberger J, Hertting K, Werner M, Branzan D, Freitas B, Piorkowski M, Schmidt A, Scheinert D. Renal denervation for hypertension refractory to renal artery stenting. J Endovasc Ther 2014; 21:181-90. [PMID: 24754276 DOI: 10.1583/13-4566r.1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
PURPOSE To investigate the effect of renal denervation (RDN) on blood pressure and renal function in refractory hypertension after renal artery recanalization and optimal medical therapy. METHODS Ten patients (6 women; mean age 70.0±5.1 years) with an office systolic blood pressure >160 mmHg despite taking ≥3 antihypertensive drugs and uni- or bilateral renal artery stenting were treated with RDN. Radiofrequency (RF) energy was delivered to the native segment of the artery keeping a 5-mm safe distance from the stented segments. Standardized office (OBP) and ambulatory (ABP) blood pressure measurements, medication, and renal assessment, including renal duplex ultrasound and renal function, were determined at baseline and on follow-up to 12 months. RESULTS OBP (systolic/diastolic) at baseline was 190.0±20.4 / 84.2±10.1 mmHg. It decreased to 171.1±28.7* / 82.2±8.7, 165.5±28.4(†) / 76.1±7.4, and 158.3±14.2(†) / 75.5±9.5(†) mmHg (*p<0.001; (†)p<0.01) at 3, 6, and 12 months after RDN, respectively. Average ABP (systolic/diastolic) after 6 and 12 months decreased by -7.6(‡) / -3.1 and -11.3(‡) / -5.1(‡) mmHg ((‡)p<0.05). There was no renal artery (re)stenosis, dissection, or aneurysm within 12 months. Creatinine, cystatin C, and glomerular filtration rate remained unchanged. Urine albumin excretion decreased in 4/10 patients. Renal resistive indices improved in native, but not in stented renal arteries within the follow-up period. CONCLUSION This proof-of-concept study demonstrates that RF-based RDN can be safely and effectively delivered in patients with resistant hypertension and previous renal artery stenting.
Collapse
Affiliation(s)
- Yvonne Bausback
- Centre of Vascular Medicine: Angiology and Vascular Surgery, Park Hospital Leipzig, Germany
| | | | | | | | | | | | | | | | | |
Collapse
|
|
16
|
Epstein M, de Marchena E. Is the failure of SYMPLICITY HTN-3 trial to meet its efficacy endpoint the "end of the road" for renal denervation? ACTA ACUST UNITED AC 2014; 9:140-9. [PMID: 25649995 DOI: 10.1016/j.jash.2014.12.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2014] [Revised: 11/30/2014] [Accepted: 12/03/2014] [Indexed: 12/11/2022]
Abstract
Resistant hypertension is a common medical problem that is increasing with the advent of an increasingly older and heavier population. The etiology of resistant hypertension is almost always multifactorial, but the results of numerous studies indicate that renal sympathetic activation is a particularly common cause of resistance to antihypertensive treatment. Consistent with the belief in a pivotal role of renal sympathetic stimulation, there has been a growing interest in renal denervation (RDN) treatment strategies. The long-awaited results of SYMPLICITY HTN-3 study disclosed that the reduction in blood pressure by the SYMPLICITY device did not differ from that in the sham-procedure arm of the study. In the present article, we identify several factors that explain why the study failed to demonstrate any benefit from the intervention. The reasons are multifactorial and include inadequate screening at entry and frequent medication changes during the study. Additional problems include the lack of experience of many operators with the SYMPLICITY device and procedure variability, as attested to by a diminished number of ablation "quadrants." Also a factor was the inability of the first generation Medtronic device to allow four ablations to be performed simultaneously. We recommend that future RDN studies adhere to more rigorous screening procedures, and utilize newer multi-site denervation systems that facilitate four ablations simultaneously. Drug optimization should be achieved by monitoring adherence throughout the study. Nevertheless, we are optimistic about a future role of RDN. To optimize chances of success, increased efforts are necessary to identify the appropriate patients for RDN and investigators must use second and third generation denervation devices and techniques.
Collapse
Affiliation(s)
- Murray Epstein
- Division of Nephrology and Hypertension, University of Miami, Leonard M. Miller School of Medicine, Miami, FL, USA.
| | - Eduardo de Marchena
- Division of Cardiology, University of Miami, Leonard M. Miller School of Medicine, Miami, FL, USA
| |
Collapse
|
|
17
|
Doumas M, Tsioufis C, Faselis C, Lazaridis A, Grassos H, Papademetriou V. Non-interventional management of resistant hypertension. World J Cardiol 2014; 6:1080-1090. [PMID: 25349652 PMCID: PMC4209434 DOI: 10.4330/wjc.v6.i10.1080] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2013] [Revised: 04/12/2014] [Accepted: 08/31/2014] [Indexed: 02/06/2023] Open
Abstract
Hypertension is one of the most popular fields of research in modern medicine due to its high prevalence and its major impact on cardiovascular risk and consequently on global health. Indeed, about one third of individuals worldwide has hypertension and is under increased long-term risk of myocardial infarction, stroke or cardiovascular death. On the other hand, resistant hypertension, the “uncontrollable” part of arterial hypertension despite appropriate therapy, comprises a much greater menace since long-standing, high levels of blood pressure along with concomitant debilitating entities such as chronic kidney disease and diabetes mellitus create a prominent high cardiovascular risk milieu. However, despite the alarming consequences, resistant hypertension and its effective management still have not received proper scientific attention. Aspects like the exact prevalence and prognosis are yet to be clarified. In an effort to manage patients with resistant hypertension appropriately, clinical doctors are still racking their brains in order to find the best therapeutic algorithm and surmount the substantial difficulties in controlling this clinical entity. This review aims to shed light on the effective management of resistant hypertension and provide practical recommendations for clinicians dealing with such patients.
Collapse
|
|
18
|
White WB, Turner JR, Sica DA, Bisognano JD, Calhoun DA, Townsend RR, Aronow HD, Bhatt DL, Bakris GL. Detection, evaluation, and treatment of severe and resistant hypertension: proceedings from an American Society of Hypertension Interactive forum held in Bethesda, MD, U.S.A., October 10th 2013. ACTA ACUST UNITED AC 2014; 8:743-57. [PMID: 25418497 DOI: 10.1016/j.jash.2014.06.005] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2014] [Accepted: 06/26/2014] [Indexed: 01/13/2023]
Abstract
The epidemiology, evaluation, and management of severe and resistant hypertension in the United States (US) are evolving. The American Society of Hypertension held a multi-disciplinary forum in October 2013 to review the available evidence related to the management of resistant hypertension with both drug and device therapies. There is strong evidence that resistant hypertension is an important clinical problem in the US and many other regions of the world. Complex drug therapy is effective in most of the patients with severe and resistant hypertension, but there are certain individuals who may be refractory to multiple-drug regimens or have adverse effects that make adherence to the regimen difficult. When secondary forms of hypertension and pseudo-resistance, such as medication nonadherence, or white-coat hypertension based on marked differences between clinic and 24-hour ambulatory blood pressure monitoring, have been excluded, the impact of device therapy is under evaluation through clinical trials in the US and from clinical practice registries in Europe and Australia. Clinical trial data have been obtained primarily in patients whose resistant hypertension is defined as systolic clinic blood pressures of ≥160 mm Hg (or ≥ 150 mm Hg in type 2 diabetes) despite pharmacologic treatment with at least three antihypertensive drugs (one of which is a thiazide or loop diuretic). Baroreceptor stimulation therapy has shown modest benefit in a moderately sized sham-controlled study in drug-resistant hypertension. Patients selected for renal denervation have typically been restricted to those with preserved kidney function (estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2). The first sham-controlled safety and efficacy trial for renal denervation (SYMPLICITY HTN-3) did not show benefit in this population when used in addition to an average of five antihypertensive medications. Analyses of controlled clinical trial data from future trials with novel designs will be of critical importance to determine the effectiveness of device therapy for patients with severe and resistant hypertension and will allow for proper determination of patient selection and whether it will be acceptable for clinical practice. At present, the focus on the management of severe and resistant hypertension will be through careful evaluation for pseudo-resistance and secondary forms of hypertension, appropriate use of combination pharmacologic therapy, and greater utility of specialists in hypertension.
Collapse
Affiliation(s)
- William B White
- Division of Hypertension and Clinical Pharmacology, Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT, USA.
| | | | - Domenic A Sica
- Virginia Commonwealth University Medical Center, Richmond, VA, USA
| | | | - David A Calhoun
- University of Alabama School of Medicine, Birmingham, AL, USA
| | - Raymond R Townsend
- Clinical & Translational Research Center at the University of Pennsylvania, Philadelphia, PA, USA
| | | | - Deepak L Bhatt
- Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | | |
Collapse
|
|
19
|
Affiliation(s)
- Vasilios Papademetriou
- From the Department of Medicine (Cardiology), Veteran Affairs Medical Center and Georgetown University, Washington, DC (V.P.); Department of Cardiology, Kapodestrian University of Athens, Athens, Greece (C.T.); and Department of Medicine, Aristotle University, Thessaloniki, Greece (M.D.)
| | - Costas Tsioufis
- From the Department of Medicine (Cardiology), Veteran Affairs Medical Center and Georgetown University, Washington, DC (V.P.); Department of Cardiology, Kapodestrian University of Athens, Athens, Greece (C.T.); and Department of Medicine, Aristotle University, Thessaloniki, Greece (M.D.)
| | - Michael Doumas
- From the Department of Medicine (Cardiology), Veteran Affairs Medical Center and Georgetown University, Washington, DC (V.P.); Department of Cardiology, Kapodestrian University of Athens, Athens, Greece (C.T.); and Department of Medicine, Aristotle University, Thessaloniki, Greece (M.D.)
| |
Collapse
|
|
20
|
Papademetriou V, Rashidi AA, Tsioufis C, Doumas M. Renal nerve ablation for resistant hypertension: how did we get here, present status, and future directions. Circulation 2014; 129:1440-51. [PMID: 24687645 DOI: 10.1161/circulationaha.113.005405] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Affiliation(s)
- Vasilios Papademetriou
- Department of Veterans Affairs and Georgetown University, Washington, DC (V.P., A.A.R.); Ippokration University Hospital, Athens, Greece (C.T.); Aristotle University of Thessaloniki, Thessaloniki, Greece (M.D.)
| | | | | | | |
Collapse
|
|
21
|
Schwerg M, Heupel C, Strajnic D, Baumann G, Laule M, Stangl V, Stangl K. Renal sympathetic denervation: early impact on ambulatory resistant hypertension. J Clin Hypertens (Greenwich) 2014; 16:406-11. [PMID: 24766570 PMCID: PMC8031809 DOI: 10.1111/jch.12326] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2014] [Revised: 02/18/2014] [Accepted: 02/23/2014] [Indexed: 11/28/2022]
Abstract
Although guidelines recommend ambulatory blood pressure (BP) monitoring (ABPM), few data are available regarding the effects of renal denervation (RDN) on 24-hour ABPM values. A total of 44 patients with mean systolic BP ≥135 mm Hg on ABPM despite adequate therapy were included. Basal systolic BP (SBP) and diastolic BP (DBP) were 154±11 mm Hg and 86±12 mm Hg, respectively. At 1 month, SBP and DBP were reduced to 146±18 mm Hg (P=.01) and 82±14 mm Hg and showed no further decrease up to 6 months. Only 55% of the patients responded to RDN (≥-5 mm Hg SBP), with a mean responder rate drop of 21/11 mm Hg. Neither the number of ablation points nor the amount of impedance drop was predictive of response. Only approximately half of patients with resistant hypertension responded to RDN. However, in these responders, a remarkable reduction of 24-hour BP occurred as early as 1 month after RDN.
Collapse
Affiliation(s)
- Marius Schwerg
- Department of Cardiology and AngiologyCampus Mitte Charité – UniversitätsmedizinBerlinGermany
| | - Christian Heupel
- Department of Cardiology and AngiologyCampus Mitte Charité – UniversitätsmedizinBerlinGermany
| | - Dino Strajnic
- Department of Cardiology and AngiologyCampus Mitte Charité – UniversitätsmedizinBerlinGermany
| | - Gert Baumann
- Department of Cardiology and AngiologyCampus Mitte Charité – UniversitätsmedizinBerlinGermany
| | - Michael Laule
- Department of Cardiology and AngiologyCampus Mitte Charité – UniversitätsmedizinBerlinGermany
| | - Verena Stangl
- Department of Cardiology and AngiologyCampus Mitte Charité – UniversitätsmedizinBerlinGermany
| | - Karl Stangl
- Department of Cardiology and AngiologyCampus Mitte Charité – UniversitätsmedizinBerlinGermany
| |
Collapse
|
|
22
|
Doumas M, Lazaridis A, Papademetriou V. Renal Nerve Ablation for Resistant Hypertension: The Dust Has Not Yet Settled. J Clin Hypertens (Greenwich) 2014; 16:399-400. [DOI: 10.1111/jch.12324] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Michael Doumas
- VAMC; George Washington University; Washington DC
- Aristotle University; Thessaloniki Greece
| | - Antonios. Lazaridis
- 2nd Propedeutic Department of Internal Medicine; Hippokration Hospital; Thessaloniki Greece
| | | |
Collapse
|
|
23
|
Persu A, O'Brien E, Verdecchia P. Use of ambulatory blood pressure measurement in the definition of resistant hypertension: a review of the evidence. Hypertens Res 2014; 37:967-72. [DOI: 10.1038/hr.2014.83] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2014] [Revised: 03/07/2014] [Accepted: 03/11/2014] [Indexed: 01/18/2023]
|
|
24
|
Ram CVS, Kumar AS. Renal denervation therapy for resistant hypertension: a clinical update. J Hum Hypertens 2014; 28:699-704. [PMID: 24599151 DOI: 10.1038/jhh.2014.6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2013] [Revised: 12/17/2013] [Accepted: 12/26/2013] [Indexed: 01/25/2023]
Abstract
Severe hypertension (systolic blood pressure (BP) ⩾160 mm Hg) resistant to treatment with multiple antihypertensive medications, poses a serious challenge to therapeutic treatment. Catheter-based renal denervation (RDN) is being increasingly proposed and researched as a safe and effective method of treating this condition. This article evaluates the existing evidence on the effects of RDN on BP reduction and other conditions with increased sympathetic tone. Findings indicate that RDN is a safe and effective treatment for severe hypertension. Moreover, the antihypertensive response to RDN is sustained for up to 3 years of follow-up. RDN decreases office BP more than ambulatory BP, which may be explained by the white-coat effect that causes an increase in office BP. Findings indicate that although reinnervation may occur following RDN, it does not appear to attenuate or reverse the BP response over 24-36 months. There is also evidence that patients with milder forms of hypertension may benefit from RDN. Furthermore, there is emerging evidence that RDN may have a role in the treatment of heart failure, obstructive sleep apnea, insulin resistance, atrial fibrillation and hypertension associated with end-stage renal disease. Taking into account that resistant hypertension and other diseases associated with elevated sympathetic tone are associated with significant morbidity and mortality rates, RDN therapy may be expected to have a significant impact on public health.
Collapse
Affiliation(s)
- C V S Ram
- 1] Apollo Institute for Blood Pressure Management, Apollo Blood Pressure Clinics, Apollo Hospitals, Hyderabad, India [2] Texas Blood Pressure Institute, University of Texas Southwestern Medical School, Dallas, TX, USA
| | - A S Kumar
- Cardiology Department, Continental Hospitals, Hyderabad, India
| |
Collapse
|
|
25
|
Howard JP, Cole GD, Sievert H, Bhatt DL, Papademetriou V, Kandzari DE, Davies JE, Francis DP. Unintentional overestimation of an expected antihypertensive effect in drug and device trials: Mechanisms and solutions. Int J Cardiol 2014; 172:29-35. [DOI: 10.1016/j.ijcard.2013.12.183] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Accepted: 12/28/2013] [Indexed: 11/30/2022]
|
|
26
|
2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2014; 31:1281-357. [PMID: 23817082 DOI: 10.1097/01.hjh.0000431740.32696.cc] [Citation(s) in RCA: 3331] [Impact Index Per Article: 302.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
|
|
27
|
Howard JP, Nowbar AN, Francis DP. Size of blood pressure reduction from renal denervation: insights from meta-analysis of antihypertensive drug trials of 4,121 patients with focus on trial design: the CONVERGE report. Heart 2013; 99:1579-87. [PMID: 24038167 DOI: 10.1136/heartjnl-2013-304238] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
OBJECTIVE 30 mm Hg drops in office systolic blood pressure are reported in trials of renal denervation, but ambulatory reductions are much smaller. This disparity is assumed to have a physiological basis and also be present with antihypertensive drugs. DESIGN We examine this office-ambulatory discrepancy through meta-analysis of drug and denervation trials, categorising by trial design. PATIENTS (STUDIES) 31 drug trials enrolling 4121 patients and 23 renal denervation trials enrolling 720 patients met the criteria. RESULTS In drug trials without randomisation or blinding, pressure reductions are 5.6 mm Hg (95% CI 2.98 to 8.22 mm Hg) larger on office measurements than ambulatory blood pressure monitoring (p<0.0001). By contrast, with randomisation and blinding, office reductions are identical to ambulatory reductions (difference -0.88 mm Hg, 95% CI -3.18 to 1.43, p=0.45). For renal denervation, there are no randomised blinded trial results. In unblinded trials, office pressure drops were 27.6 mm Hg versus pretreatment, and 26.6 mm Hg versus unintervened controls. By contrast, ambulatory pressure drops averaged 15.7 mm Hg across all trials. Among those where the baseline ambulatory pressure was not the deciding factor for enrolment (avoiding regression to the mean), ambulatory drops averaged only 11.9 mm Hg. CONCLUSIONS Discrepancies in drug trials between office and ambulatory blood pressure reductions disappear once double-blinded placebo control is implemented. Renal denervation trials may also undergo similar evolution. We predict that as denervation trial designs gradually improve in bias-resistance, office and ambulatory pressure drops will converge. We predict that it is the office drops that will move to match the ambulatory drops, that is, not 30, but nearer 13.
Collapse
Affiliation(s)
- James P Howard
- International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, , London, UK
| | | | | |
Collapse
|
|
28
|
Myat A, Redwood SR, Qureshi AC, Thackray S, Cleland JGF, Bhatt DL, Williams B, Gersh BJ. Renal sympathetic denervation therapy for resistant hypertension: a contemporary synopsis and future implications. Circ Cardiovasc Interv 2013; 6:184-97. [PMID: 23591420 DOI: 10.1161/circinterventions.112.000037] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Aung Myat
- King's College London BHF Centre of Research Excellence, London, United Kingdom
| | | | | | | | | | | | | | | |
Collapse
|
|
29
|
Blood pressure changes after renal denervation at 10 European expert centers. J Hum Hypertens 2013; 28:150-6. [PMID: 24067345 PMCID: PMC3932403 DOI: 10.1038/jhh.2013.88] [Citation(s) in RCA: 121] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2013] [Revised: 08/05/2013] [Accepted: 08/09/2013] [Indexed: 12/16/2022]
Abstract
We did a subject-level meta-analysis of the changes (Δ) in blood pressure (BP) observed 3 and 6 months after renal denervation (RDN) at 10 European centers. Recruited patients (n=109; 46.8% women; mean age 58.2 years) had essential hypertension confirmed by ambulatory BP. From baseline to 6 months, treatment score declined slightly from 4.7 to 4.4 drugs per day. Systolic/diastolic BP fell by 17.6/7.1 mm Hg for office BP, and by 5.9/3.5, 6.2/3.4, and 4.4/2.5 mm Hg for 24-h, daytime and nighttime BP (P⩽0.03 for all). In 47 patients with 3- and 6-month ambulatory measurements, systolic BP did not change between these two time points (P⩾0.08). Normalization was a systolic BP of <140 mm Hg on office measurement or <130 mm Hg on 24-h monitoring and improvement was a fall of ⩾10 mm Hg, irrespective of measurement technique. For office BP, at 6 months, normalization, improvement or no decrease occurred in 22.9, 59.6 and 22.9% of patients, respectively; for 24-h BP, these proportions were 14.7, 31.2 and 34.9%, respectively. Higher baseline BP predicted greater BP fall at follow-up; higher baseline serum creatinine was associated with lower probability of improvement of 24-h BP (odds ratio for 20-μmol l−1 increase, 0.60; P=0.05) and higher probability of experiencing no BP decrease (OR, 1.66; P=0.01). In conclusion, BP responses to RDN include regression-to-the-mean and remain to be consolidated in randomized trials based on ambulatory BP monitoring. For now, RDN should remain the last resort in patients in whom all other ways to control BP failed, and it must be cautiously used in patients with renal impairment.
Collapse
|
|
30
|
Turner JR, O'Brien E. Diagnosis and Treatment of Resistant Hypertension: The Critical Role of Ambulatory Blood Pressure Monitoring. J Clin Hypertens (Greenwich) 2013; 15:868-73. [DOI: 10.1111/jch.12200] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Revised: 08/14/2013] [Accepted: 08/15/2013] [Indexed: 12/29/2022]
Affiliation(s)
| | - Eoin O'Brien
- The Conway Institute; University College Dublin; Dublin Ireland
| |
Collapse
|
|
31
|
The possibility of resistant hypertension during the treatment of hypertensive patients. Hypertens Res 2013; 36:924-9. [PMID: 24026036 DOI: 10.1038/hr.2013.107] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2012] [Revised: 07/22/2013] [Accepted: 07/25/2013] [Indexed: 02/07/2023]
Abstract
Patients with poorly controlled hypertension despite taking at least three different kinds of anti-hypertensive drugs, including diuretics, are considered to have resistant hypertension (RH). The prevalence of RH was reported to be 13% in the Japanese J-HOME study. The incidences of RH in younger and older Japanese individuals should be prospectively investigated in the near future. RH is associated with poor outcomes and various cardiovascular events. In addition, it is frequently associated with older age, obesity, sleep apnea, long-term hypertension, diabetes, dyslipidemia, reduced renal function, microalbuminuria and left ventricular hypertrophy. Some cases of RH exhibit high levels of aldosterone and cortisol, suggesting that endocrine hypertension should be ruled out among RH patients. Carotid baroreceptor activation and renal sympathetic denervation have recently been developed as treatments for RH. In conclusion, we should consider the possibility of RH during the treatment of hypertensive patients who do not achieve appropriate blood pressure control, in order to avoid the early onset of fatal cardiovascular events and reduce medical costs.
Collapse
|
|
32
|
Feldman RD, Brass EP. From bad behaviour to bad biology: pitfalls and promises in the management of resistant hypertension. Can J Cardiol 2013; 29:549-56. [PMID: 23618504 DOI: 10.1016/j.cjca.2013.02.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2012] [Revised: 02/12/2013] [Accepted: 02/12/2013] [Indexed: 10/26/2022] Open
Abstract
Control rates for hypertension have dramatically improved during the past 2 decades-especially in Canada. However, hypertension remains one of the top risk factors for premature death globally. Furthermore, one-third of Canadians with hypertension have not obtained adequate blood pressure control. Most of these patients have resistant hypertension with uncontrolled blood pressure despite therapy. The etiology of resistant hypertension is multifactorial but includes both behavioural and biological factors. Among behavioural factors, nonadherence on the part of patients and especially clinical inertia on the part of health care professionals are contributing causes. An understanding of the root causes underlying the failure to control an individual's blood pressure is central to optimal subsequent management. Further advances in blood pressure control rates in this group of patients will depend on improvements in health care delivery systems and the further development of innovative therapies. Drugs combining multiple antihypertensive agents in a single pill and the development of new technologies to lower blood pressure, primarily by disruption of the sympathetic nervous system, have the potential to be useful strategies in this effort.
Collapse
Affiliation(s)
- Ross D Feldman
- Department of Medicine, Schulich School of Medicine and Dentistry, University of Western Ontario, Ontario, Canada.
| | | |
Collapse
|
|
33
|
Abstract
Renal afferent and efferent sympathetic nerves are involved in the regulation of blood pressure and have a pathophysiological role in hypertension. Renal sympathetic denervation is a novel therapeutic technique for the treatment of patients with resistant hypertension. Clinical trials of renal sympathetic denervation have shown significant reductions in blood pressure in these patients. Renal sympathetic denervation also reduces heart rate, which is a surrogate marker of cardiovascular risk. Conditions that are comorbid with hypertension, such as heart failure and myocardial hypertrophy, obstructive sleep apnoea, atrial fibrillation, renal dysfunction, and metabolic syndrome are closely associated with enhanced sympathetic activity. In experimental models and case-control studies, renal denervation has had beneficial effects on these conditions. Renal denervation could become a commonly used procedure to treat resistant hypertension and chronic diseases associated with enhanced sympathetic activation. Current work is focused on refining the techniques and interventional devices to provide safe and effective renal sympathetic denervation. Controlled studies in patients with mild-to-moderate, nonresistant hypertension and comorbid conditions such as heart failure, diabetes mellitus, sleep apnoea, and arrhythmias are needed to investigate the capability of renal sympathetic denervation to improve cardiovascular outcomes.
Collapse
|
|
34
|
Mahfoud F, Ukena C, Schmieder RE, Cremers B, Rump LC, Vonend O, Weil J, Schmidt M, Hoppe UC, Zeller T, Bauer A, Ott C, Blessing E, Sobotka PA, Krum H, Schlaich M, Esler M, Böhm M. Ambulatory blood pressure changes after renal sympathetic denervation in patients with resistant hypertension. Circulation 2013; 128:132-40. [PMID: 23780578 DOI: 10.1161/circulationaha.112.000949] [Citation(s) in RCA: 215] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Catheter-based renal sympathetic denervation (RDN) reduces office blood pressure (BP) in patients with resistant hypertension according to office BP. Less is known about the effect of RDN on 24-hour BP measured by ambulatory BP monitoring and correlates of response in individuals with true or pseudoresistant hypertension. METHODS AND RESULTS A total of 346 uncontrolled hypertensive patients, separated according to daytime ambulatory BP monitoring into 303 with true resistant (office systolic BP [SBP] 172.2±22 mm Hg; 24-hour SBP 154±16.2 mm Hg) and 43 with pseudoresistant hypertension (office SBP 161.2±20.3 mm Hg; 24-hour SBP 121.1±19.6 mm Hg), from 10 centers were studied. At 3, 6, and 12 months follow-up, office SBP was reduced by 21.5/23.7/27.3 mm Hg, office diastolic BP by 8.9/9.5/11.7 mm Hg, and pulse pressure by 13.4/14.2/14.9 mm Hg (n=245/236/90; P for all <0.001), respectively. In patients with true treatment resistance there was a significant reduction with RDN in 24-hour SBP (-10.1/-10.2/-11.7 mm Hg, P<0.001), diastolic BP (-4.8/-4.9/-7.4 mm Hg, P<0.001), maximum SBP (-11.7/-10.0/-6.1 mm Hg, P<0.001) and minimum SBP (-6.0/-9.4/-13.1 mm Hg, P<0.001) at 3, 6, and 12 months, respectively. There was no effect on ambulatory BP monitoring in pseudoresistant patients, whereas office BP was reduced to a similar extent. RDN was equally effective in reducing BP in different subgroups of patients. Office SBP at baseline was the only independent correlate of BP response. CONCLUSIONS RDN reduced office BP and improved relevant aspects of ambulatory BP monitoring, commonly linked to high cardiovascular risk, in patients with true-treatment resistant hypertension, whereas it only affected office BP in pseudoresistant hypertension.
Collapse
Affiliation(s)
- Felix Mahfoud
- Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Kirrberger Str, Geb 40, 66421 Homburg/Saar, Germany.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
35
|
|
|
36
|
Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F, Redon J, Dominiczak A, Narkiewicz K, Nilsson PM, Burnier M, Viigimaa M, Ambrosioni E, Caufield M, Coca A, Olsen MH, Schmieder RE, Tsioufis C, van de Borne P, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Clement DL, Coca A, Gillebert TC, Tendera M, Rosei EA, Ambrosioni E, Anker SD, Bauersachs J, Hitij JB, Caulfield M, De Buyzere M, De Geest S, Derumeaux GA, Erdine S, Farsang C, Funck-Brentano C, Gerc V, Germano G, Gielen S, Haller H, Hoes AW, Jordan J, Kahan T, Komajda M, Lovic D, Mahrholdt H, Olsen MH, Ostergren J, Parati G, Perk J, Polonia J, Popescu BA, Reiner Z, Rydén L, Sirenko Y, Stanton A, et alMancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, Christiaens T, Cifkova R, De Backer G, Dominiczak A, Galderisi M, Grobbee DE, Jaarsma T, Kirchhof P, Kjeldsen SE, Laurent S, Manolis AJ, Nilsson PM, Ruilope LM, Schmieder RE, Sirnes PA, Sleight P, Viigimaa M, Waeber B, Zannad F, Redon J, Dominiczak A, Narkiewicz K, Nilsson PM, Burnier M, Viigimaa M, Ambrosioni E, Caufield M, Coca A, Olsen MH, Schmieder RE, Tsioufis C, van de Borne P, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, Clement DL, Coca A, Gillebert TC, Tendera M, Rosei EA, Ambrosioni E, Anker SD, Bauersachs J, Hitij JB, Caulfield M, De Buyzere M, De Geest S, Derumeaux GA, Erdine S, Farsang C, Funck-Brentano C, Gerc V, Germano G, Gielen S, Haller H, Hoes AW, Jordan J, Kahan T, Komajda M, Lovic D, Mahrholdt H, Olsen MH, Ostergren J, Parati G, Perk J, Polonia J, Popescu BA, Reiner Z, Rydén L, Sirenko Y, Stanton A, Struijker-Boudier H, Tsioufis C, van de Borne P, Vlachopoulos C, Volpe M, Wood DA. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013; 34:2159-219. [PMID: 23771844 DOI: 10.1093/eurheartj/eht151] [Show More Authors] [Citation(s) in RCA: 3225] [Impact Index Per Article: 268.8] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- Giuseppe Mancia
- Centro di Fisiologia Clinica e Ipertensione, Università Milano-Bicocca, Milano, Italy.
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
37
|
Grassi G, Bombelli M, Seravalle G, Brambilla G, Dell’Oro R, Mancia G. Role of Ambulatory Blood Pressure Monitoring in Resistant Hypertension. Curr Hypertens Rep 2013; 15:232-237. [DOI: 10.1007/s11906-013-0349-0] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
|
|
38
|
Interpreting treatment-induced blood pressure reductions measured by ambulatory blood pressure monitoring. J Hum Hypertens 2013; 27:715-20. [DOI: 10.1038/jhh.2013.39] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2013] [Revised: 03/19/2013] [Accepted: 03/26/2013] [Indexed: 11/08/2022]
|
|
39
|
Muxfeldt ES, de Souza F, Salles GF. Resistant hypertension: a practical clinical approach. J Hum Hypertens 2013; 27:657-62. [DOI: 10.1038/jhh.2013.34] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2013] [Revised: 03/17/2013] [Accepted: 03/26/2013] [Indexed: 12/28/2022]
|
|
40
|
Persu A, Renkin J, Thijs L, Staessen JA. Renal denervation: ultima ratio or standard in treatment-resistant hypertension. Hypertension 2012; 60:596-606. [PMID: 22851728 DOI: 10.1161/hypertensionaha.112.195263] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Alexandre Persu
- Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, Belgium
| | | | | | | |
Collapse
|