Denervación simpática renal en el tratamiento de la hipertensión arterial resistente / Renal sympathetic denervation for the management of resistant hypertension

INTRODUCCIÓN: La hipertensión arterial resistente se define como aquella con valores superiores a 140/90 mmHg a pesar del tratamiento antihipertensivo con al menos 3 medicaciones a dosis óptimas, incluyendo un diurético. La denervación simpática renal se ha propuesto como una alternativa terapéutica de la hipertensión arterial resistente. Los resultados de los ensayos clínicos llevados a cabo para valorar la efectividad y seguridad de esta técnica han arrojado resultados contradictorios. OBJETIVOS: El objetivo principal de este informe es evaluar la efectividad y seguridad de la denervación renal en comparación a los cuidados estándar para el tratamiento de la hipertensión arterial resistente; mientras que los objetivos secundarios son: a) evaluar la efectividad de la denervación renal en comparación a los cuidados estándar para el tratamiento de la hipertensión renal resistente a fármacos en términos de mortalidad, control de la presión arterial, calidad de vida, morbilidad cardiovascular, función renal, ingresos hospitalarios y disminución del tratamiento farmacológico a medio y largo plazo; b) evaluar la seguridad de la denervación renal en comparación a los cuidados estándar para el tratamiento de la hipertensión arterial resistente a fármacos en términos de complicaciones específicas de la técnica y efectos adversos a medio y largo plazo; c) evaluar el grado de aceptabilidad y satisfacción del paciente con la denervación renal en comparación a los cuidados estándar; y d) evaluar el impacto económico, organizativo y estructural asociado a la implementación de la denervación renal. MÉTODOS: Se ha realizado una búsqueda de la literatura científica, desde 2013 hasta enero de 2023, en las siguientes bases de datos: Bases de datos especializadas en Revisiones Sistemáticas e Informes de evaluación de tecnologías sanitarias, tales como RedETS, BRISA, Epistemonikos, International HTA database o la Cochrane Library. Bases de datos generales, como Medline y Embase. Bases de datos generales, como Medline y Embase. Se seleccionaron ensayos clínicos para evaluar la efectividad y seguridad, y estudios observacionales y cualitativos para evaluar la aceptabilidad y satisfacción de los pacientes. Dos revisores independientes revisaron y seleccionaron los artículos siguiendo unos criterios de selección previamente establecidos. Esta información se sintetizó en las tablas de evidencia y se realizó un metanálisis de los resultados cuando fue posible. Resultados: Del resultado de la búsqueda bibliográfica se seleccionaron los 28 artículos que cumplían los criterios de selección que se habían prefijado, correspondiéndose con 11 ensayos clínicos. Además, se seleccionaron 5 estudios observacionales para evaluar la aceptabilidad y la satisfacción de los pacientes. Los resultados obtenidos no sugieren que la denervación renal disminuya significativamente la presión arterial a los 6 meses. En función del tipo de comparador usado (procedimiento de simulación, medicación antihipertensiva de base u optimización del tratamiento antihipertensivo), la denervación renal disminuye 7.70 mmHg (IC95% 13.11-2.29) la presión arterial sistólica y 4.03 mmHg (IC95% 7.56-0.49) la presión arterial diastólica en comparación con la medicación antihipertensiva de base, pero no en comparación con los otros dos comparadores. La denervación renal no parece cambiar el riesgo de hipertrofia ventricular izquierda, los niveles de creatinina plasmática ni la tasa de filtración glomerular a los 6 meses tras la intervención. Tampoco se ha observado una disminución significativa del tratamiento antihipertensivo a los 6 meses, en comparación con el procedimiento simulado o el tratamiento antihipertensivo. En cuanto a seguridad, la denervación renal no parece impactar sobre el riesgo de infarto agudo de miocardio, accidentes cerebrovasculares, fibrilación auricular, crisis antihipertensivas ni episodios de hipotensión. Los eventos adversos del procedimiento fueron más comunes en el grupo intervención que en el grupo control (14.3% vs. 8.3%). De los ensayos que reportaron mortalidad, el 81.8% de las muertes se reportó en el grupo intervención frente al 18.2% en el grupo control. En cuanto a los resultados de aceptabilidad y satisfacción de la denervación renal, entre el 28.2% y el 47.0% de los participantes hipertensos aceptarían someterse a la denervación renal. Se observó que los hombres y las personas más jóvenes mostraban una mayor probabilidad de aceptar someterse a denervación renal. DISCUSIÓN: Todos los ensayos clínicos incluidos evaluaron la denervación renal mediante radiofrecuencia.Los resultados de efectividad muestran que la denervación renal disminuye la presión arterial en comparación con el tratamiento antihipertensivo de base, pero no al optimizar el tratamiento o al realizar un procedimiento simulado. Los resultados sugieren que la denervación renal no disminuye el número de medicaciones antihipertensivas de los pacientes. En cuanto seguridad, es incierto el efecto que causa la denervación renal más allá de los 6 meses tras intervención. Si bien, no se han reportado eventos adversos graves en los estudios incluidos. No ha sido posible, ni para efectividad ni para seguridad, evaluar la denervación renal a largo plazo, debido a que no se obtuvieron los suficientes datos para realizar metanálisis a los 12, 24 y 36 meses tras la intervención. Tampoco ha sido posible evaluar la denervación renal utilizando otros métodos que no fueran radiofrecuencia, pues ningún ensayo clínico de denervación renal con ultrasonidos o alcohol cumplió con los criterios de selección preestablecidos para ser incluidos en el informe. CONCLUSIONES: Los resultados sugieren que la denervación renal no parece ser superior en términos de efectividad y seguridad en comparación con el tratamiento antihipertensivo optimizado o un procedimiento simulado a los 6 meses. Los resultados sugieren un efecto beneficioso de la denervación renal en comparación con el tratamiento antihipertensivo de base. En cuanto a los efectos a medio/largo plazo, no disponemos de evidencia suficiente para concluir si la denervación renal es superior a su comparador. Es necesario que los futuros ensayos clínicos sobre denervación renal tengan un seguimiento largo y tamaños muestrales suficientes para evaluar estos aspectos a largo plazo, además de no ofrecer denervación renal a los sujetos del grupo control tras 6 meses del inicio del ensayo.

INTRODUCTION: Resistant arterial hypertension is defined as that with values above 140/90 mmHg despite antihypertensive treatment with at least 3 medications at optimal doses, including a diuretic. Renal sympathetic denervation has been proposed as a therapeutic alternative for resistant arterial hypertension. The results of clinical trials carried out to assess the effectiveness and safety of this technique have yielded contradictory results. OBJECTIVES: The primary aim of this report is to evaluate the effectiveness and safety of renal denervation compared to standard care for the treatment of resistant arterial hypertension; while the secondary objectives are: (a) to evaluate the effectiveness of renal denervation compared to standard care for the treatment of drug-resistant renal hypertension in terms of mortality, blood pressure control, quality of life, cardiovascular morbidity, renal function, hospital admissions, and decreased drug treatment in the medium and long term; b) to evaluate the safety of renal denervation compared to standard care for the treatment of drug-resistant hypertension in terms of technique-specific complications and medium- and long-term adverse effects; c) to evaluate the degree of patient acceptability and satisfaction with renal denervation compared to standard care; and d) to evaluate the economic, organizational and structural impact associated with the implementation of renal denervation. METHODS: A search of the scientific literature, since 2013 to January 2023, was carried out in the following databases: Databases specialized in Systematic Reviews and Health Technology Assessment Reports, such as RedETS, BRISA, Epistemonikos, International HTA database or the Cochrane Library. General databases, such as Medline and Embase. Clinical trials were selected to assess effectiveness and safety, and observational and qualitative studies to assess acceptability and patient satisfaction. Two independent reviewers reviewed and selected the articles following previously established selection criteria. This information was synthesized in the evidence tables and a meta-analysis of the results was performed when possible. RESULTS: From the results of the bibliographic search, the 28 articles that met the preset selection criteria were selected, corresponding to 11 clinical trials. In addition, 5 observational studies were selected to evaluate acceptability and patient satisfaction. The results obtained do not suggest that renal denervation significantly lowers blood pressure at 6 months. Depending on the type of comparator used (sham procedure, baseline antihypertensive medication or optimization of antihypertensive treatment), renal denervation decreases 7.70 mmHg (95%CI 13.11-2.29) systolic blood pressure and 4.03 mmHg (95%CI 7.56- 0.49) diastolic blood pressure compared to baseline antihypertensive medication, but not compared to the other two comparators. Renal denervation does not appear to change the risk of left ventricular hypertrophy, plasma creatinine levels or glomerular filtration rate at 6 months after the intervention. Nor has a significant decrease in antihypertensive treatment been observed at 6 months compared with the sham procedure or antihypertensive treatment. In terms of safety, renal denervation did not appear to impact the risk of acute myocardial infarction, stroke, atrial fibrillation, antihypertensive crisis, or hypotensive episodes. Procedural adverse events were more common in the intervention group than in the control group (14.3% vs. 8.3%). Of the trials reporting mortality, 81.8% of deaths were reported in the intervention group vs. 18.2% in the control group. Regarding the results of acceptability and satisfaction with renal denervation, between 28.2% and 47.0% of hypertensive participants would accept undergoing renal denervation. It was observed that men and younger people showed a higher likelihood of accepting to undergo renal denervation. DISCUSSION: All included clinical trials evaluated radiofrequency renal denervation. Effectiveness results show that renal denervation lowers blood pressure compared to baseline antihypertensive treatment, but not when optimizing treatment or performing a sham procedure. The results suggest that renal denervation does not reduce the number of antihypertensive medications in patients. In terms of safety, the effect of renal denervation beyond 6 months after intervention is uncertain. However, no serious adverse events have been reported in the included studies. It has not been possible, either for effectiveness or safety, to evaluate long-term renal denervation, because insufficient data were obtained to perform meta-analyses at 12, 24 and 36 months after the intervention. Nor has it been possible to evaluate renal denervation using methods other than radiofrequency, as no clinical trials of renal denervation with ultrasound or alcohol met the preestablished selection criteria for inclusion in the report. CONCLUSIONS: The results suggest that renal denervation does not appear to be superior in terms of effectiveness and safety compared with optimized antihypertensive treatment or a sham procedure at 6 months. The results suggest a beneficial effect of renal denervation compared with baseline antihypertensive treatment. Regarding medium/long-term effects, we do not have sufficient evidence to conclude whether renal denervation is superior to its comparator. Future clinical trials on renal denervation need to have a long follow-up and sufficient sample sizes to evaluate these aspects in the long term, in addition to not offering renal denervation to subjects in the control group after 6 months from the start of the trial.

Nationwide Cross-sectional Analysis of Endoscopic Thoracic Sympathectomy to Treat Hyperhidrosis Over 12 years in Brazil: Epidemiology, Costs, and Mortality.

OBJECTIVE: To analyze the number of endoscopic thoracic sympathectomies performed to treat hyperhidrosis in the Universal Public Health System of Brazil, the government reimbursements, and the in-hospital mortality rates. BACKGROUND: Even though endoscopic thoracic sympathectomy has been widely performed for the definitive treatment of hyperhidrosis, no series reported mortality and there are no population-based studies evaluating its costs or its mortality rate. METHODS: Data referring to endoscopic thoracic sympathectomy to treat hyperhidrosis between 2008 and 2019 were extracted from the database of the Brazilian Public Health System, which insures more than 160 million inhabitants. RESULTS: Thirteen thousand two hundred one endoscopic thoracic sympathectomies to treat hyperhidrosis were performed from 2008 to 2019, with a rate of 68.44 procedures per 10 million inhabitants per year. There were 6 in-hospital deaths during the whole period, representing a mortality rate of 0.045%. The total expended throughout the years was U$ 6,767,825.14, with an average of U$ 512.68 per patient. CONCLUSIONS: We observed a rate of 68.44 thoracoscopic sympathectomies for hyperhidrosis' treatment per 10 million inhabitants per year. The inhospital mortality rate was very low, 0.045%, though not nil. To our knowledge, no published series is larger than ours and we are the first authors to formally report deaths after endoscopic thoracic sympathectomies to treat hyperhidrosis. Moreover, there is no other population-based study addressing costs and mortality rates of every endoscopic thoracic sympathectomy for the treatment of any site of hyperhidrosis in a given period.

Assessment of arterial stiffness to predict blood pressure response to renal sympathetic denervation.

BACKGROUND: Recent trials support the efficacy of renal sympathetic denervation (RDN) to reduce blood pressure (BP). Nevertheless, about one third of patients are considered non-responders to RDN. Previous retrospective analyses suggest arterial stiffness could predict BP response to RDN. AIMS: We prospectively assessed the potential of invasive pulse wave velocity (iPWV) to predict BP response to RDN. Additionally, we aimed to establish non-invasive models based on arterial stiffness to predict BP response to RDN. METHODS:  iPWV, magnetic resonance imaging-based markers of arterial stiffness and the carotid-femoral pulse wave velocity were recorded prior to RDN in patients with treatment resistant hypertension. Changes in daytime BP after 3 months were analysed according to the prespecified iPWV cut-off (14.4 m/s). Regression analyses were used to establish models for non-invasive prediction of BP response. Results were compared to iPWV as reference and were then validated in an external patient cohort. RESULTS: Eighty patients underwent stiffness assessment before RDN. After 3 months, systolic 24h and daytime BP were reduced by 13.6±9.8 mmHg and 14.7±10.6 mmHg in patients with low iPWV, versus 6.2±13.3 mmHg and 6.3±12.8 mmHg in those with high iPWV (p<0.001 for both). Upon regression analysis, logarithmic ascending aortic distensibility and systolic baseline BP independently predicted BP change at follow-up. Both were confirmed in the validation cohort. CONCLUSIONS:  iPWV is an independent predictor for BP response after RDN. In addition, BP change prediction following RDN using non-invasive measures is feasible. This could facilitate patient selection for RDN treatment.

Thoracoscopic sympathectomy decreases disease burden in patients with medically refractory ventricular arrhythmias.

OBJECTIVES: Thoracic sympathectomy has been shown to be effective in reducing implantable cardioverter-defibrillator (ICD) shocks and ventricular tachycardia recurrence in patients with channelopathies, but the evidence supporting its use for refractory ventricular arrhythmias in patients without channelopathies is limited. This is a single-centre cohort study of bilateral R1-R4 thoracoscopic sympathectomy for medically refractory ventricular arrhythmias. METHODS: Clinical information was examined for all bilateral thoracoscopic R1-R4 sympathectomies for ventricular arrhythmias at our institution from 2016 through 2020. RESULTS: Thirteen patients underwent bilateral thoracoscopic R1-R4 sympathectomy. All patients had prior ICD implant. Patients had a recent history of multiple ICD discharges (12/13), catheter ablation (10/13) and cardiac arrest (3/13). Ten patients were urgently operated on following transfer to our centre for sustained ventricular tachycardia. Seven patients had ventricular tachycardia ablations preoperatively during the same admission. Five patients were in intensive care immediately preoperatively, with 3 requiring mechanical ventilation. Three patients suffered in-hospital mortality. Kaplan-Meier analysis estimated 73% overall survival at 24-month follow-up. Among the 10 patients who survived to discharge, all were alive at a median follow-up of 8.7 months (interquartile range 0.6-26.7 months). Six of 10 patients had no further ICD discharges. Kaplan-Meier analysis estimated 27% ICD shock-free survival at 24 months follow-up for all patients. Three of 10 patients had additional ablations, while 2 patients underwent cardiac transplantation. CONCLUSIONS: Bilateral thoracoscopic sympathectomy is an effective option for patients with life-threatening ventricular arrhythmia refractory to pharmacotherapy and catheter ablation.

Comprehensive Assessment of Human Accessory Renal Artery Periarterial Renal Sympathetic Nerve Distribution.

OBJECTIVES: The aim of this study was to understand the anatomy of periarterial nerve distribution in human accessory renal arteries (ARAs). BACKGROUND: Renal denervation is a promising technique for blood pressure control. Despite the high prevalence of ARAs, the anatomic distribution of periarterial nerves around ARAs remains unknown. METHODS: Kidneys with surrounding tissues were collected from human autopsy subjects, and histological evaluation was performed using morphometric software. An ARA was defined as an artery arising from the aorta above or below the dominant renal artery (DRA) or an artery that bifurcated within 20 mm of the takeoff of the DRA from the aorta. The DRA was defined as an artery that perfused >50% of the kidney. RESULTS: A total of 7,287 nerves from 14 ARAs and 9 DRAs were evaluated. The number of nerves was smaller in the ARA than DRA (median: 30 [interquartile range: 17.5 to 48.5] vs. 49 [interquartile range: 36 to 76]; p < 0.0001). In both ARAs and DRAs, the distance from the arterial lumen to nerve was shortest in the distal, followed by the middle and proximal segments. On the basis of the post-mortem angiography, ARAs were divided into large (≥3 mm diameter) and small (<3 mm) groups. The number of nerves was greatest in the DRA, followed by the large and small ARA groups (53 [41 to 97], 38 [25 to 53], and 24.5 [10.5 to 36.3], respectively; p = 0.001). CONCLUSIONS: ARAs showed a smaller number of nerves than DRAs, but these results were dependent on the size of the ARA. Ablation, especially in large ARAs, may allow more complete denervation with the potential to further reduce blood pressure.

Hyperhidrosis, Endoscopic Thoracic Sympathectomy, and Cardiovascular Outcomes: A Cohort Study Based on the Korean Health Insurance Review and Assessment Service Database.

Sympathetic overactivity is associated with hyperhidrosis and cardiovascular diseases. Endoscopic thoracic sympathectomy (ETS) is a treatment for hyperhidrosis. We aimed to compare the risk for cardiovascular events between individuals with and without hyperhidrosis and investigate the effects of ETS on cardiovascular outcomes. We conducted a nationwide population-based cohort study using data acquired from the Korean Health Insurance Review and Assessment Service. Subjects newly diagnosed with hyperhidrosis in 2010 were identified and divided into two groups according to whether or not they underwent ETS. Propensity scores were calculated using a logistic regression model to match hyperhidrosis patients with control subjects. Combined cardiovascular events were defined as stroke and ischemic heart diseases. Subjects were followed up until the first cardiovascular event or 31 December 2017. The risk for cardiovascular events with hyperhidrosis and ETS was analyzed using Cox proportional hazards regression analysis. The risk for stroke was significantly higher in the hyperhidrosis group than in the control group (hazard ratio (HR), 1.28; 95% confidence interval (CI), 1.08-1.51); nonetheless, no significant difference in the risk for ischemic heart diseases was observed between the hyperhidrosis group and the control group (HR, 1.17; 95% CI, 0.99-1.31). Hyperhidrosis patients who did not undergo ETS were at significantly higher risk for cardiovascular events than the control group (HR, 1.28; 95% CI, 1.13-1.45). However, no significant difference in the risk for cardiovascular events was observed between hyperhidrosis patients who underwent ETS and the control group. Hyperhidrosis increases the risk for cardiovascular events. ETS could reduce this risk and needs to be considered for high-risk patients with cardiovascular diseases.

Evaluation of Quality of Life: Functional Assessment of Chronic Illness Therapy after Thoracic Sympathectomy for Palmar Hyperhidrosis.

BACKGROUND: Primary hyperhidrosis is a condition that significantly decreases the quality of life (QOL). Thoracic sympathectomy is safe and efficient method of treatment in palmar hyperhidrosis. OBJECTIVE: The aim of the study was to evaluate the change in QOL in patients with palmar hyperhidrosis who underwent thoracic sympathectomy. METHODS: The study includes 149 patients (37 men and 112 women) who were treated with bilateral thoracoscopic sympathectomy for primary palmar hyperhidrosis. Subjective and objective evaluation of hyperhidrosis were performed prior to the surgery, 3 and 12 months after the treatment. Control group consists of 305 healthy volunteers (118 men and 187 women). The QOL was measured using Functional Assessment of Chronic Illness Therapy (FACIT) scale. RESULTS: The average level of palmar hyperhidrosis in the study group prior to surgery was 224.69 ± 179.20 mg/min/m2. General QOL (FACIT total) before the surgery was significantly lower in the study group when compared with the control group (66.57 ± 16.33 vs. 91.29 ± 11.13; p < 0.05). Three months after surgery level of hyperhidrosis decreased significantly and remained at similar level 12 months after the procedure (13.55 ± 15.41 mg/min/m2 p < 0.05 and 14.41 ± 18.19 mg/min/m2 p < 0.05, respectively). After thoracoscopic sympathectomy, the QOL increased and did not differ when compared with the control group 3 and 12 months after the surgery (90.28 ± 11.13 vs. 91.29 ± 11.13; p = 0.55 and 89.59 ± 11.34 vs. 91.29 ± 11.13; p = 0.84, respectively). The highest increase was observed in functional well-being domain (32.25%); however, it was also noticeable in other domains. CONCLUSION: Thoracic sympathectomy is an efficient method of treatment in palmar hyperhidrosis which significantly increases patients' QOL especially in a functional domain.

Cardiac magnetic resonance assessment of central and peripheral vascular function in patients undergoing renal sympathetic denervation as predictor for blood pressure response.

BACKGROUND: Most trials regarding catheter-based renal sympathetic denervation (RDN) describe a proportion of patients without blood pressure response. Recently, we were able to show arterial stiffness, measured by invasive pulse wave velocity (IPWV), seems to be an excellent predictor for blood pressure response. However, given the invasiveness, IPWV is less suitable as a selection criterion for patients undergoing RDN. Consequently, we aimed to investigate the value of cardiac magnetic resonance (CMR) based measures of arterial stiffness in predicting the outcome of RDN compared to IPWV as reference. METHODS: Patients underwent CMR prior to RDN to assess ascending aortic distensibility (AAD), total arterial compliance (TAC), and systemic vascular resistance (SVR). In a second step, central aortic blood pressure was estimated from ascending aortic area change and flow sequences and used to re-calculate total arterial compliance (cTAC). Additionally, IPWV was acquired. RESULTS: Thirty-two patients (24 responders and 8 non-responders) were available for analysis. AAD, TAC and cTAC were higher in responders, IPWV was higher in non-responders. SVR was not different between the groups. Patients with AAD, cTAC or TAC above median and IPWV below median had significantly better BP response. Receiver operating characteristic (ROC) curves predicting blood pressure response for IPWV, AAD, cTAC and TAC revealed areas under the curve of 0.849, 0.828, 0.776 and 0.753 (p = 0.004, 0.006, 0.021 and 0.035). CONCLUSIONS: Beyond IPWV, AAD, cTAC and TAC appear as useful outcome predictors for RDN in patients with hypertension. CMR-derived markers of arterial stiffness might serve as non-invasive selection criteria for RDN.

Retroperitoneoscopic lumbar sympathectomy for plantar hyperhidrosis.

OBJECTIVE: The objective of this study was to assess the reduction in quality of life (QoL) caused by the persistence of primary plantar hyperhidrosis (PPH) symptoms and the level of satisfaction in PPH patients after retroperitoneoscopic lumbar sympathectomy (RLS). The efficacy, safety, and procedure of bilateral RLS in both sexes are also described in this study. METHODS: This is a longitudinal study of consecutive patients who sought specific treatment from a private practitioner for severe PPH as classified on the Hyperhidrosis Disease Severity Scale (HDSS) from October 2005 to October 2014. The patients were asked to report the symptoms of PPH experienced in the immediate preoperative period and to complete a standardized QoL questionnaire developed by de Campos at least 12 months after RLS. Disease outcomes, recurrence of symptoms, and any adverse effects of surgery were evaluated after 30 days and at least 12 months after RLS. RESULTS: Lumbar sympathectomy was performed 116 times in 58 patients; 30 days after surgery, PPH was resolved in all patients. Three patients (5.2%) reported transient thigh neuralgia, and 19 (32.7%) reported transient paresthesia in the lower limbs. There were no reports of retrograde ejaculation. At a minimum of 12 months after RLS, 49 of the 58 patients had fully and correctly answered the follow-up questionnaire and noted a mild (HDSS 2) to moderate (HDSS 3) increase in pre-existing compensatory sweating. One patient had a PPH relapse within 6 months. Improvement in QoL due to the resolution of PPH was reported in 98% of the 49 patients. None of the operations necessitated a change in the laparotomy approach, and none of the patients died. CONCLUSIONS: RLS is safe and effective for the treatment of severe PPH in both sexes. There were no reports of retrograde ejaculation after resection of L3 and L4 ganglia. There was a mild to moderate increase in compensatory sweating in about half of the patients, but without any regret or dissatisfaction for having undergone the surgery because of a significant improvement in QoL.

Account for Clinical Heterogeneity in Assessment of Catheter-based Renal Denervation among Resistant Hypertension Patients: Subgroup Meta-analysis.

BACKGROUND: Catheter-based renal denervation (RDN) is a novel treatment for resistant hypertension (RH). A recent meta-analysis reported that RDN did not significantly reduce blood pressure (BP) based on the pooled effects with mild to severe heterogeneity. The aim of the present study was to identify and reduce clinical sources of heterogeneity and reassess the safety and efficacy of RDN within the identified homogeneous subpopulations. METHODS: This was a meta-analysis of 9 randomized clinical trials (RCTs) among patients with RH up to June 2016. Sensitivity analyses and subgroup analyses were extensively conducted by baseline systolic blood pressure (SBP) level, antihypertensive medication change rates, and coronary heart disease (CHD). RESULTS: In all patients with RH, no statistical differences were found in mortality, severe cardiovascular events rate, and changes in 24-h SBP and office SBP at 6 and 12 months. However, subgroup analyses showed significant differences between the RDN and control groups. In the subpopulations with baseline 24-h SBP ≥155 mmHg (1 mmHg = 0.133 kPa) and the infrequently changed medication, the use of RDN resulted in a significant reduction in 24-h SBP level at 6 months (P = 0.100 and P= 0.009, respectively). Subgrouping RCTs with a higher prevalent CHD in control showed that the control treatment was significantly better than RDN in office SBP reduction at 6 months (P < 0.001). CONCLUSIONS: In all patients with RH, the catheter-based RDN is not more effective in lowering ambulatory or office BP than an optimized antihypertensive drug treatment at 6 and 12 months. However, among RH patients with higher baseline SBP, RDN might be more effective in reducing SBP.

Renal artery and parenchymal changes after renal denervation: assessment by magnetic resonance angiography.

OBJECTIVES: Relatively little is known about the incidence of long-term renal damage after renal denervation (RDN), a potential new treatment for hypertension. In this study the incidence of renal artery and parenchymal changes, assessed with contrast-enhanced magnetic resonance angiography (MRA) after RDN, is investigated. METHODS: This study is an initiative of ENCOReD, a collaboration of hypertension expert centres. Patients in whom an MRA was performed before and after RDN were included. Scans were evaluated by two independent, blinded radiologists. Primary outcome was the change in renal artery morphology and parenchyma. RESULTS: MRAs from 96 patients were analysed. Before RDN, 41 renal anomalies were observed, of which 29 mostly mild renal artery stenoses. After a median time of 366 days post RDN, MRA showed a new stenosis (25-49% lumen reduction) in two patients and progression of pre-existing lumen reduction in a single patient. No other renal changes were observed and renal function remained stable. CONCLUSIONS: We observed new or progressed renal artery stenosis in three out of 96 patients, after a median time of 12 months post RDN (3.1%). Procedural angiographies showed that ablations were applied near the observed stenosis in only one of the three patients. KEY POINTS: • The incidence of vascular changes 12 months post RDN was 3.1%. • No renal vascular or parenchymal changes other than stenoses were observed. • Ablations were applied near the stenosis in only one of three patients.

Quality of Life Changes Following Surgery for Hyperhidrosis.

The best way to evaluate the impact of primary hyperhidrosis on quality of life (QL) is through specific questionnaires, avoiding generic models that do not appropriately evaluate individuals. QL improves significantly in the short term after sympathectomy. In the longer term, a sustained and stable improvement is seen, although there is a small decline in the numbers; after 5 and even at 10 years of follow-up it shows virtually the same numerical distribution. Compensatory hyperhidrosis is a major side effect and the main aggravating factor in postoperative QL, requiring attention to its management and prevention.

Experience with botulinum toxin therapy for axillary hyperhidrosis and comparison to modelled data for endoscopic thoracic sympathectomy - A quality of life and cost effectiveness analysis.

AIM: To estimate cost-effectiveness of botulinum toxin therapy for axillary hyperhidrosis compared to the standard surgical intervention of endoscopic thoracic sympathectomy (ETS). METHODS: The validated dermatology life quality index questionnaire was given to patients attending for treatment over a 4 month period, to assess their quality of life (QoL) over the preceding week (n = 44). Follow-up was performed 4-6 weeks later by telephone using the same questionnaire to validate the effectiveness of the treatment. The duration of effect of the botulinum toxin treatment was also recorded and this data was used as the basis for cost effectiveness analysis. Using HIPE data, the baseline cost for single intervention using botulinum toxin and ETS was retrieved. Using figures provided by HIPE and expert opinion of the costs of complications, a stochastic model for 10,000 patients was used to evaluate the total costs for ETS including the complications. RESULTS: The results from the QoL analysis show that botulinum toxin therapy is a successful therapy for improvement of symptoms. It was revealed that the mean interval before recurrence of original symptoms after botulinum toxin therapy was 5.6 months. The baseline cost for both treatments are €389 for botulinum toxin and €9389 for uncomplicated ETS. The stochastic model yields a mean cost of €11,390 for ETS including complications. CONCLUSIONS: Treatments reached cost equivalence after 13.3 years. However, given the efficacy of the botulinum toxin therapy and the low risk we propose that botulinum toxin therapy for hyperhidrosis should be considered the gold standard.

Assessment of hypertension control and clinical course of patients excluded from the SYMPLICITY HTN-3 trial.

The screening of patients referred for the Symplicity Renal-Denervation Catheter Therapy on Resistant Hypertension (SYMPLICITY HTN-3) trial was rigorous, with many found not eligible to participate. We investigate patients who were not included in the trial and evaluate their current hypertensive (HTN) therapy, control and clinical status. A retrospective review and telephone interview was performed 8-10 months postscreening on 45 patients and their referring providers who were ultimately not included. Patients were grouped into 4 categories: (1) noninterest; (2) excluded (not meeting inclusion criteria); (3) screen failure (excluded during screening visits due to adequate blood pressure control guided by HTN specialist); or (4) referred after enrollment closure. Primary outcomes evaluated included current anti-HTN management and clinical outcomes. This population consisted of 42% males, mean age 65 ± 5 years, 78% African American, 64% diabetic, and 21% chronic kidney disease. Primary referral basis included cardiology (44%), nephrology (30%), and primary care (26%). At time of follow-up, 20% had continued resistant HTN while most of the patients had controlled HTN (60%); with highest success rates among the screen failure group (88%) who also had the lowest average systolic blood pressure (137 ± 11 mm of Hg) when compared to other groups (P = .04). Average number of medications was lowest in the screen failure group (2.8 ± 1.6, P = .07). Resistant and/or uncontrolled HTN was most prevalent in the noninterest or excluded groups, as were hospitalization for cardiovascular and HTN urgency/emergency. This study highlights the disparity of HTN control and treatment in daily practice compared with clinical trials, and confirms a need for vigilant screening of those considered candidates for renal denervation.

Multimodality Intra-Arterial Imaging Assessment of the Vascular Trauma Induced by Balloon-Based and Nonballoon-Based Renal Denervation Systems.

BACKGROUND: Renal denervation is a new treatment considered for several possible indications. As new systems are introduced, the incidence of acute renal artery wall injury with relation to the denervation method is unknown. We investigated the acute repercussion of renal denervation on the renal arteries of patients treated with balloon-based and nonballoon-based denervation systems by quantitative angiography, intravascular ultrasound, and optical coherence tomography (OCT). METHODS AND RESULTS: Twenty-five patients (50 renal arteries) underwent bilateral renal denervation with 5 different systems, 3 of which balloon-based (Paradise [n=5], Oneshot [n=6], and Vessix V2 [n=5)]) and 2 nonballoon-based (Symplicity [n=6] and EnligHTN [n=3]). Analysis included quantitative angiography and morphometric intravascular ultrasound measurements pre and post procedure and assessment of vascular trauma (dissection, edema, or thrombus) by OCT after denervation. A significant reduction in lumen size by quantitative angiography and intravascular ultrasound was observed in nonballoon denervation but not in balloon denervation. By postdenervation OCT, dissection was seen in 14 arteries (32.6%). The percentage of frames with dissection was higher in balloon-based denervation catheters. Thrombus and edema were detected in 35 (81.4%) and 32 (74.4%) arteries, respectively. In arteries treated with balloon-based denervation that had dissection by OCT, the balloon/artery ratio was higher (1.24 [1.17-1.32] versus 1.10 [1.04-1.18]; P<0.01). CONCLUSIONS: A varying extent of vascular injury was observed after renal denervation in all systems; however, different patterns were identified in balloon-based and in nonballoon-based denervation systems. In balloon denervation, the presence of dissections by OCT was associated with a higher balloon/artery ratio.