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1.
Lancet ; 395(10234): 1444-1451, 2020 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-32234534

RESUMEN

BACKGROUND: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. METHODS: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749. FINDINGS: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months. INTERPRETATION: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. FUNDING: Medtronic.


Asunto(s)
Hipertensión/cirugía , Riñón/inervación , Riñón/cirugía , Adulto , Antihipertensivos/normas , Australia/epidemiología , Austria/epidemiología , Teorema de Bayes , Presión Sanguínea/fisiología , Canadá/epidemiología , Femenino , Alemania/epidemiología , Grecia/epidemiología , Humanos , Hipertensión/diagnóstico , Hipertensión/etnología , Irlanda/epidemiología , Japón/epidemiología , Riñón/fisiopatología , Masculino , Persona de Mediana Edad , Placebos/efectos adversos , Estudios Prospectivos , Simpatectomía/métodos , Resultado del Tratamiento , Reino Unido/epidemiología , Estados Unidos/epidemiología
2.
EuroIntervention ; 16(1): 89-96, 2020 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-32038027

RESUMEN

AIMS: We aimed to estimate the rate of renal artery adverse events following renal denervation with the most commonly applied radiofrequency catheter system based on a comprehensive review of published reports. METHODS AND RESULTS: We reviewed 50 published renal denervation (RDN) trials reporting on procedural safety including 5,769 subjects with 10,249 patient-years of follow-up. Twenty-six patients with renal artery stenosis or dissection (0.45%) were identified of whom 24 (0.41%) required renal artery stenting. The primary meta-analysis of all reports indicated a 0.20% pooled annual incidence rate of stent implantation (95% CI: 0.12 to 0.29% per year). Additional sensitivity analyses yielded consistent pooled estimates (range: 0.17 to 0.42% per year). Median time from RDN procedure to all renal intervention was 5.5 months (range: 0 to 33 months); 79% of all events occurred within one year of the procedure. A separate review of 14 clinical trials reporting on prospective follow-up imaging using either magnetic resonance imaging, computed tomography or angiography following RDN in 511 total subjects identified just 1 new significant stenosis (0.20%) after a median of 11 months post procedure (one to 36 months). CONCLUSIONS: Renal artery reintervention following renal denervation with the most commonly applied RF renal denervation system (Symplicity) is rare. Most events were identified within one year.


Asunto(s)
Ablación por Catéter/efectos adversos , Desnervación/efectos adversos , Arteria Renal/lesiones , Arteria Renal/efectos de la radiación , Simpatectomía/métodos , Antihipertensivos , Presión Sanguínea , Humanos , Hipertensión/cirugía , Riñón/fisiopatología , Arteria Renal/inervación , Simpatectomía/efectos adversos , Resultado del Tratamiento
3.
JAMA ; 323(3): 248-255, 2020 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-31961420

RESUMEN

Importance: Renal denervation can reduce cardiac sympathetic activity that may result in an antiarrhythmic effect on atrial fibrillation. Objective: To determine whether renal denervation when added to pulmonary vein isolation enhances long-term antiarrhythmic efficacy. Design, Setting, and Participants: The Evaluate Renal Denervation in Addition to Catheter Ablation to Eliminate Atrial Fibrillation (ERADICATE-AF) trial was an investigator-initiated, multicenter, single-blind, randomized clinical trial conducted at 5 referral centers for catheter ablation of atrial fibrillation in the Russian Federation, Poland, and Germany. A total of 302 patients with hypertension despite taking at least 1 antihypertensive medication, paroxysmal atrial fibrillation, and plans for ablation were enrolled from April 2013 to March 2018. Follow-up concluded in March 2019. Interventions: Patients were randomized to either pulmonary vein isolation alone (n = 148) or pulmonary vein isolation plus renal denervation (n = 154). Complete pulmonary vein isolation to v an end point of elimination of all pulmonary vein potentials; renal denervation using an irrigated-tip ablation catheter delivering radiofrequency energy to discrete sites in a spiral pattern from distal to proximal in both renal arteries. Main Outcomes and Measures: The primary end point was freedom from atrial fibrillation, atrial flutter, or atrial tachycardia at 12 months. Secondary end points included procedural complications within 30 days and blood pressure control at 6 and 12 months. Results: Of the 302 randomized patients (median age, 60 years [interquartile range, 55-65 years]; 182 men [60.3%]), 283 (93.7%) completed the trial. All successfully underwent their assigned procedures. Freedom from atrial fibrillation, flutter, or tachycardia at 12 months was observed in 84 of 148 (56.5%) of those undergoing pulmonary vein isolation alone and in 111 of 154 (72.1%) of those undergoing pulmonary vein isolation plus renal denervation (hazard ratio, 0.57; 95% CI, 0.38 to 0.85; P = .006). Of 5 prespecified secondary end points, 4 are reported and 3 differed between groups. Mean systolic blood pressure from baseline to 12 months decreased from 151 mm Hg to 147 mm Hg in the isolation-only group and from 150 mm Hg to 135 mm Hg in the renal denervation group (between-group difference, -13 mm Hg; 95% CI, -15 to -11 mm Hg; P < .001). Procedural complications occurred in 7 patients (4.7%) in the isolation-only group and 7 (4.5%) of the renal denervation group. Conclusions and Relevance: Among patients with paroxysmal atrial fibrillation and hypertension, renal denervation added to catheter ablation, compared with catheter ablation alone, significantly increased the likelihood of freedom from atrial fibrillation at 12 months. The lack of a formal sham-control renal denervation procedure should be considered in interpreting the results of this trial. Trial Registration: ClinicalTrials.gov Identifier: NCT01873352.


Asunto(s)
Fibrilación Atrial/cirugía , Ablación por Catéter , Hipertensión/cirugía , Riñón/inervación , Venas Pulmonares/cirugía , Simpatectomía , Anciano , Antihipertensivos/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/prevención & control , Terapia Combinada , Resistencia a Medicamentos , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Prevención Secundaria , Método Simple Ciego
4.
Prog Cardiovasc Dis ; 63(1): 51-57, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31884099

RESUMEN

Hypertension affects millions of Americans and has adverse long-term consequences increasing morbidity and mortality. Resistant hypertension (RH) continues to be difficult to treat with medications alone which may be associated with significant side effects. Alternate therapies have been evaluated for treating RH and renal denervation has been investigated extensively. We review the data from renal denervation trials and other novel technologies which are not FDA approved to date.


Asunto(s)
Técnicas de Ablación , Presión Sanguínea , Resistencia a Medicamentos , Hipertensión/cirugía , Riñón/irrigación sanguínea , Arteria Renal/inervación , Simpatectomía , Técnicas de Ablación/efectos adversos , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Quimioterapia Combinada , Humanos , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/fisiopatología , Factores de Riesgo , Simpatectomía/efectos adversos , Resultado del Tratamiento
5.
BMC Neurol ; 19(1): 341, 2019 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-31881866

RESUMEN

BACKGROUND: To evaluate the efficacy of microvascular decompression (MVD) in reducing hypertension (HTN) in hypertensive patients with trigeminal neuralgia (TN). METHODS: The clinical data of 58 cases of neurogenic HTN with TN treated in our hospital were retrospectively reviewed. Preoperative MR revealed abnormal blood pressure in the left rostral ventrolateral medulla (RVLM) and the posterior cranial nerve root entry zone (REZ). The patients were divided into control group: only trigeminal nerve was treated with MVD; experimental group: trigeminal nerve, RVLM and REZ were treated with MVD at the same time. The patients were followed up for 6 months to 1 year to observe the changes of blood pressure. RESULTS: There was no significant difference in gender, age, course of TN, course of HTN, grade of HTN and preoperative blood pressure between the two groups. After operation, the effective rate of HTN improvement with MVD was 32.1% in the control group. There was no significant difference in the preoperative and post operative blood pressure. (P△SBP = 0.131; P△BDP = 0.078). In the experimental group, the effective rate was 83.3%. The postoperative blood pressure was significantly lower than preoperative values. (P△SBP < 0.001; P△DBP < 0.001). CONCLUSIONS: MVD is an effective treatment for neurogenic HTN. However, the criteria for selecting hypertensive patients who need MVD to control their HTN still needs to be further determined. Possible indications may include: left trigeminal neuralgia, neurogenic HTN; abnormal blood pressure compression in the left RVLM and REZ areas on MR; and blood pressure in these patients can not be effectively controlled by drugs.


Asunto(s)
Hipertensión/etiología , Hipertensión/cirugía , Bulbo Raquídeo/cirugía , Cirugía para Descompresión Microvascular/métodos , Enfermedades Vasculares/cirugía , Adulto , Anciano , Femenino , Humanos , Masculino , Bulbo Raquídeo/patología , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Neuralgia del Trigémino/etiología , Neuralgia del Trigémino/cirugía , Enfermedades Vasculares/complicaciones
6.
Adv Clin Exp Med ; 28(11): 1525-1530, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31693316

RESUMEN

BACKGROUND: With emerging new therapeutic concepts including renal denervation (RDN), there is a renewed interest in resistant hypertension (ResH). Among patients suspected of having ResH, a definitive diagnosis needs to be established. OBJECTIVES: This study presents observations from a standardized single-center screening program for RDN candidates, including medical therapy modification and reassessment. MATERIAL AND METHODS: All patients referred to our center for RDN underwent a standardized screening protocol. Candidates were recruited from among patients receiving no less than 3 antihypertensive drugs, including diuretics with office blood pressure (BP) >140/90 mm Hg. The assessment included 2 measurements of BP and ambulatory BP monitoring (ABPM). If needed, pharmacotherapy was intensified and the diagnosis of ResH was reconfirmed after 6 weeks. If ResH was persistent, patients were hospitalized with repeated ABPM on day 4. Further, renal CT-angio was performed and a multidisciplinary team discussed the patients' suitability for RDN. RESULTS: A total of 87 patients with a ResH diagnosis were referred for RDN. Mean office BP was 159/92 (±7.0/6.5) mm Hg and mean ABPM was 154/90 (±9.0/4.8) mm Hg. The initial medication included angiotensin convertase inhibitors (ACE-I, 78%), angiotensin receptor blockers (12%), ß-blockers (85%), calcium channel blockers (36%), and diuretics (93%). During the 18 months of the RDN program, 5 patients underwent RDN and 2 further had ineligible renal anatomy. A new diagnosis of secondary hypertension was made in 21 patients. However, in 59 patients, BP control was achieved after optimization of medical therapy, with a mean ABPM of 124/74 mm Hg. The final treatment included ACE-I (100%), ß-blockers (92%), indapamide (94%), amlodipine (72%), and spironolactone (61%). Medication in most of these patients (88%) included single-pill triple combination (52.5%) or double combination (35.6%). CONCLUSIONS: Patients with elevated BP screened for RDN require a rigorous diagnostic workup. Up to 2/3 of patients can be managed with strict pharmacotherapy compliance and pharmaceutical intensification, including single-pill combinations and improved drug compliance. Hasty use of RDN may be a result of poor drug optimization and/or compliance. It does remain a viable treatment option in thoroughly vetted ResH patients.


Asunto(s)
Desnervación , Hipertensión/cirugía , Farmacovigilancia , Arteria Renal/cirugía , Antihipertensivos/uso terapéutico , Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial , Humanos , Hipertensión/tratamiento farmacológico , Riñón/inervación , Riñón/cirugía , Arteria Renal/inervación , Simpatectomía , Resultado del Tratamiento
7.
Cardiovasc J Afr ; 30(5): 290-296, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31746943

RESUMEN

The purpose of this review is to update the reader on the relevance of autonomic nervous system imbalance in clinical cardiology. Increased sympathetic tone associates with the metabolic syndrome, hypertension and cardiac arrhythmias. With the kidneys playing a pivotal role in increased peripheral resistance, sodium and water retention and other mechanisms, renal denervation (RD) may theoretically restore autonomic imbalance and improve cardiovascular outcomes. Landmark RD trials and novel uses for RD in cardiac arrhythmia management are discussed.


Asunto(s)
Fibrilación Atrial/cirugía , Desnervación Autonómica/tendencias , Sistema Nervioso Autónomo/cirugía , Hipertensión/cirugía , Riñón/inervación , Animales , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/mortalidad , Fibrilación Atrial/fisiopatología , Desnervación Autonómica/efectos adversos , Sistema Nervioso Autónomo/fisiopatología , Difusión de Innovaciones , Medicina Basada en la Evidencia , Predicción , Humanos , Hipertensión/diagnóstico , Hipertensión/mortalidad , Hipertensión/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Resultado del Tratamiento
8.
Endocrinol Metab Clin North Am ; 48(4): 875-885, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31655782

RESUMEN

Increased hormonal secretion of aldosterone, cortisol, or catecholamines from an adrenal gland can produce a variety of undesirable symptoms, including hypertension, which may be the initial presenting symptom. Consequences of secondary hypertension can result in potential cardiovascular and cerebrovascular complications at higher rates than in those with essential hypertension. Once a biochemical diagnosis is confirmed, targeted pharmacotherapy can be initiated to improve hypertension and may be corrected with surgical intervention. Adrenalectomy can be curative and can reverse the risk of cardiovascular sequelae once blood pressure control is achieved. This article discusses perioperative and operative considerations of adrenal causes of hypertension.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía , Hiperfunción de las Glándulas Suprarrenales/cirugía , Síndrome de Cushing/cirugía , Hiperaldosteronismo/cirugía , Hipertensión/cirugía , Feocromocitoma/cirugía , Neoplasias de las Glándulas Suprarrenales/complicaciones , Hiperfunción de las Glándulas Suprarrenales/complicaciones , Síndrome de Cushing/complicaciones , Humanos , Hiperaldosteronismo/complicaciones , Hipertensión/etiología , Feocromocitoma/complicaciones
9.
Kardiol Pol ; 77(10): 902-907, 2019 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-31571674

RESUMEN

Every 5 to 6 years, international and national guidelines provide updated recommendations for the standard management of hypertension in adults. Thus, within the last 18 months, societies from Europe (European Society of Cardiology and European Society of Hypertension), America (American College of Cardiology and American Heart Association), and Great Britain (National Institute for Health and Care Excellence) published their new guidelines. Despite the fact that all of them are supposedly based on the most recent clinical evidence, there are always some discrepancies between recommendations due to different interpretation of clinical trials. The purpose of the present review is to discuss 6 issues that have generated some controversies, namely, the definition of hypertension, identification of patients who should be treated, target blood pressure, pertinence of reducing salt intake, and the role of renal denervation in resistant hypertension.


Asunto(s)
Antihipertensivos/uso terapéutico , Dieta Hiposódica , Manejo de la Enfermedad , Hipertensión/tratamiento farmacológico , Humanos , Hipertensión/dietoterapia , Hipertensión/cirugía , Guías de Práctica Clínica como Asunto
10.
J Pediatr Endocrinol Metab ; 32(10): 1193-1197, 2019 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-31490776

RESUMEN

Background Pheochromocytomas (PCCs) and paragangliomas (PGLs) are known to physicians as the "great mimickers" because of their variable presentation, especially in the pediatric population. Rarely, they co-secrete other hormones. Case presentation An 11-year-old boy presented with severe hypertension (HTN) with cardiac target organ damage. Signs of genital and cutaneous androgenization were observed, but the gonadal volume was prepubertal (2 mL). Urine normetanephrine and norepinephrine levels were elevated. Increased beta-human chorionic gonadotropin (ß-HCG) and pubertal testosterone values with suppressed values of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) suggested an androgenization secondary to HCG hyperproduction. Imaging revealed a right adrenal mass, suggestive for PCC. Histopathology confirmed a PCC with positive staining for ß-HCG. Postoperative resolution of symptoms of ß-HCG and catecholamine excess and normalization of hormonal levels confirmed the diagnosis. Conclusions Ectopic hormone secretion from PCC is possible, even if rare. Signs and symptoms attributable to ectopic hormones should be investigated in PCC patients. To date, this is the first case of a ß-HCG-secreting PCC.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/complicaciones , Catecolaminas/metabolismo , Gonadotropina Coriónica Humana de Subunidad beta/metabolismo , Hiperandrogenismo/patología , Hipertensión/patología , Feocromocitoma/complicaciones , Índice de Severidad de la Enfermedad , Neoplasias de las Glándulas Suprarrenales/metabolismo , Adrenalectomía , Niño , Humanos , Hiperandrogenismo/etiología , Hiperandrogenismo/cirugía , Hipertensión/etiología , Hipertensión/cirugía , Masculino , Feocromocitoma/metabolismo , Pronóstico
11.
Obes Surg ; 29(10): 3165-3173, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31388962

RESUMEN

INTRODUCTION: Recently, a single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) has become increasingly popular for patients with BMI > 50 as a primary or staged surgery. Staging allows surgeons to do the sleeve gastrectomy (SG) first with the conversion only happening when a failure or technical challenge is identified. PURPOSE: We present the mid-term outcomes of SADI bypass surgery after SG. METHOD: A retrospective analysis was performed on a prospective database from four institutions. Ninety-six patients were identified from 2013 to 2018. Patients were divided into two groups: one had two-stage SADI because of insufficient weight loss, the second had planned two-stage SADI because of super obesity (BMI > 50 kg/m2). Incidence of complications was divided into < 30 days and > 30 days. RESULT: Of 96 patients, 3 patients were completely lost to follow-up. The mean age was 44.8 ± 11.3 years. There were no deaths or conversion to open surgery. The postoperative early complication and late complication rate was 5.3% and 6.4% respectively. At 24 months, group 2 had higher %weight loss (WL) and change in BMI units compared to group 1 with statistically significant difference. The average WL and change in BMI for entire patient's population at 24 months after 2nd stage SADI was 20.5% and 9.4 units respectively. The remission rate for DM was 93.7% with or without the use of medication. CONCLUSION: The two-stage approach to SADI-S appears technically simpler than a single compromised operation. However, this approach needs more patients to understand its limitations.


Asunto(s)
Anastomosis Quirúrgica , Duodeno/cirugía , Gastrectomía , Íleon/cirugía , Adulto , Femenino , Humanos , Hiperparatiroidismo/epidemiología , Hipertensión/cirugía , Tiempo de Internación/estadística & datos numéricos , Lípidos/sangre , Masculino , Persona de Mediana Edad , Obesidad Mórbida/cirugía , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias , Reoperación , Estudios Retrospectivos , Estados Unidos/epidemiología , Vitamina K 1/sangre , Pérdida de Peso , Zinc/sangre
12.
Mayo Clin Proc ; 94(9): 1695-1706, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31402054

RESUMEN

OBJECTIVE: To assess the efficacy and safety of catheter-based renal denervation (RDN) for the treatment of uncontrolled hypertension by conducting a systematic review and a meta-analysis. METHODS: The Medline, Cochrane Library, and Embase databases were searched for clinical studies between January 1, 2009, and July 16, 2018. Studies that evaluated the effect of RDN on uncontrolled hypertension were identified. The primary endpoints were changes in 24-hour ambulatory systolic blood pressure (BP) and office systolic BP. The secondary endpoints included changes in 24-hour ambulatory diastolic BP, office diastolic BP, and major adverse events. RESULTS: After a literature search and detailed evaluation, 12 randomized controlled trials with a total of 1539 individuals were included in the quantitative analysis. Pooled analyses indicated that RDN was associated with a significantly greater reduction of 24-hour systolic BP (mean difference [MD], -4.02 mm Hg; 95% CI, -5.49 to -2.56; P<.001) and office systolic BP (MD, -8.93 mm Hg; 95% CI, -14.03 to -3.83; P<.001) than controls. Similarly, RDN significantly reduced 24-hour diastolic BP (MD, -2.05 mm Hg; 95% CI, -3.05 to -1.05; P<.001) and office diastolic BP (MD, -4.49 mm Hg; 95% CI, -6.46 to -2.52; P<.001). RDN was not associated with an increased risk of major adverse events (relative risk, 1.06; 95% CI, 0.72 to 1.57; P=.76). CONCLUSIONS: Catheter-based RDN was associated with a significant BP-lowering benefit without increasing major adverse events.


Asunto(s)
Desnervación Autonómica/métodos , Ablación por Catéter/métodos , Hipertensión/diagnóstico , Hipertensión/cirugía , Riñón/cirugía , Adulto , Anciano , Electrocardiografía Ambulatoria/métodos , Femenino , Humanos , Riñón/inervación , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
13.
Am J Physiol Heart Circ Physiol ; 317(5): H1002-H1012, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31469293

RESUMEN

Percutaneous creation of a small central arteriovenous (AV) fistula is currently being evaluated for the treatment of uncontrolled hypertension (HT). Although the mechanisms that contribute to the antihypertensive effects of the fistula are unclear, investigators have speculated that chronic blood pressure (BP) lowering may be due to 1) reduced total peripheral resistance (TPR), 2) increased secretion of atrial natriuretic peptide (ANP), and/or 3) suppression of renal sympathetic nerve activity (RSNA). We used an established integrative mathematical model of human physiology to investigate these possibilities from baseline conditions that mimic sympathetic overactivity and impaired renal function in patients with resistant HT. After a small fistula was stimulated, there were sustained increases in cardiac output, atrial pressures, and plasma ANP concentration (3-fold), without suppression of RSNA; at 8 wk, BP was reduced 14 mmHg along with a 32% fall in TPR. In contrast, when this simulation was repeated while clamping ANP at baseline BP decreased only 4 mmHg, despite a comparable fall in TPR. Furthermore, when chronic resetting of atrial mechanoreceptors was prevented during the fistula, RSNA decreased 7%, and along with the same threefold increase in ANP, BP fell 19 mmHg. This exaggerated fall in BP occurred with a similar decrease in TPR when compared with the above simulations. These findings suggest that ANP, but not TPR, is a key determinant of long-term BP lowering after the creation of an AV fistula and support a contribution of suppressed RSNA if resetting of the atrial-renal reflex is truly incomplete.NEW & NOTEWORTHY The mechanisms that contribute to the antihypertensive effects of a small arteriovenous (AV) fistula comparable to the size used by the ROX coupler currently in clinical trials are unclear and not readily testable in clinical or experimental studies. The integrative mathematical model of human physiology used in the current study provides a tool for understanding key causal relationships that account for blood pressure (BP) lowering and for testing competing hypotheses. The findings from the simulations suggest that after creation of a small AV fistula increased ANP secretion plays a critical role in mediating long-term reductions in BP. Measurement of natriuretic peptide levels in hypertensive patients implanted with the ROX coupler would provide one critical test of this hypothesis.


Asunto(s)
Derivación Arteriovenosa Quirúrgica , Presión Atrial , Presión Sanguínea , Gasto Cardíaco , Atrios Cardíacos/inervación , Hipertensión/cirugía , Riñón/inervación , Mecanorreceptores/metabolismo , Modelos Cardiovasculares , Sistema Nervioso Simpático/fisiopatología , Antihipertensivos/uso terapéutico , Factor Natriurético Atrial/sangre , Presión Sanguínea/efectos de los fármacos , Simulación por Computador , Resistencia a Medicamentos , Humanos , Hipertensión/sangre , Hipertensión/fisiopatología , Reflejo , Factores de Tiempo
14.
Hypertension ; 74(3): 536-545, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31327262

RESUMEN

Renal nerve stimulation (RNS) can result in substantial blood pressure (BP) elevation, and the change was significantly blunted when repeated stimulation after ablation. However, whether RNS could provide a meaningful renal nerve mapping for identification of optimal ablation targets in renal denervation (RDN) is not fully clear. Here, we compared the antihypertensive effects of selective RDN guided by two different BP responses to RNS and explored the nerve innervations at these sites in Kunming dogs. Our data indicated that ablation at strong-response sites showed a more systolic BP-lowering effect than at weak-response sites (P=0.002), as well as lower levels of tyrosine hydroxylase and norepinephrine in kidney and a greater reduction in plasma norepinephrine (P=0.004 for tyrosine hydroxylase, P=0.002 for both renal and plasma norepinephrine). Strong-response sites showed a greater total area and mean number of renal nerves than weak-response sites (P=0.012 for total area and P<0.001 for mean number). Systolic BP-elevation response to RNS before RDN and blunted systolic BP-elevation to RNS after RDN were correlated with systolic BP changes at 4 weeks follow-up (R=0.649; P=0.012 and R=0.643; P=0.013). Changes of plasma norepinephrine and renal norepinephrine levels at 4 weeks were also correlated with systolic BP changes at 4 weeks (R=0.837, P<0.001 and R=0.927, P<0.001). These data suggest that selective RDN at sites with strong BP-elevation response to RNS could lead to a more efficient RDN. RNS is an effective method to identify the nerve-enriched area during RDN procedure and improve the efficacy of RDN.


Asunto(s)
Ablación por Catéter/métodos , Estimulación Eléctrica/métodos , Hipertensión/cirugía , Nervios Esplácnicos/cirugía , Simpatectomía/métodos , Análisis de Varianza , Animales , Determinación de la Presión Sanguínea/métodos , Modelos Animales de Enfermedad , Perros , Femenino , Hipertensión/fisiopatología , Riñón/inervación , Masculino , Norepinefrina/sangre , Distribución Aleatoria , Valores de Referencia , Cirugía Asistida por Computador/métodos , Resultado del Tratamiento
15.
Hypertension ; 74(3): 546-554, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31303108

RESUMEN

Radiofrequency renal denervation is under investigation for treatment of hypertension with variable success. We developed preclinical models to examine the dependence of ablation biomarkers on renal denervation treatment parameters and anatomic variables. One hundred twenty-nine porcine renal arteries were denervated with an irrigated radiofrequency catheter with multiple helically arrayed electrodes. Nerve effects and ablation geometries at 7 days were characterized histomorphometrically and correlated with associated renal norepinephrine levels. Norepinephrine exhibited a threshold dependence on the percentage of affected nerves across the range of treatment durations (30-60 s) and power set points (6-20 W). For 15 W/30 s treatments, norepinephrine reduction and percentage of affected nerves tracked with number of electrode treatments, confirming additive effects of helically staggered ablations. Threshold effects were only attained when ≥4 electrodes were powered. Histomorphometry and computational modeling both illustrated that radiofrequency treatments directed at large neighboring veins resulted in subaverage ablation areas and, therefore, contributed suboptimally to efficacy. Account for measured nerve distribution patterns and the annular geometry of the artery revealed that, regardless of treatment variables, total ablation area and circumferential coverage were the prime determinants of renal denervation efficacy, with increased efficacy at smaller diameters.


Asunto(s)
Ablación por Catéter/métodos , Hipertensión/cirugía , Riñón/inervación , Norepinefrina/sangre , Arteria Renal/cirugía , Simpatectomía/métodos , Animales , Biopsia con Aguja , Modelos Animales de Enfermedad , Electrodos , Femenino , Humanos , Hipertensión/fisiopatología , Inmunohistoquímica , Masculino , Distribución Aleatoria , Valores de Referencia , Porcinos , Resultado del Tratamiento
16.
Curr Opin Nephrol Hypertens ; 28(5): 498-506, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31268917

RESUMEN

PURPOSE OF REVIEW: Although sound physiological principles and surgical precedent underpin renal denervation as a therapy for treatment resistant hypertension, and early clinical studies had produced encouraging results, the first sham-controlled study (SYMPLICITY HTN-3) failed to achieve its primary efficacy endpoint. Lessons learnt from this trial, and the knowledge derived from further animal and autopsy work, have been applied in three recently published sham-controlled trials. RECENT FINDINGS: These trials - SPYRAL OFF-MED, RADIANCE SOLO and SPYRAL ON-MED - using newer technologies, demonstrate a 5-10 mmHg incremental reduction in ambulatory SBP from RDN against sham-control, in patients with mild-to-moderate hypertension taking 0-3 drugs. SUMMARY: These results provide proof of principle of the blood pressure-lowering effect of renal denervation. We now require data on long-term safety and durability of the procedure. Research is needed to identify predictive markers of response as about one-third of individuals do not respond to renal denervation. Hard-outcome data would be welcome but might be difficult to acquire. Individuals with treatment resistance are obvious treatment candidates, but RDN may also potentially benefit those with medication nonadherence and/or intolerance and those unwilling to take pills.


Asunto(s)
Hipertensión/cirugía , Riñón/inervación , Simpatectomía/métodos , Ensayos Clínicos como Asunto , Humanos , Hipertensión/fisiopatología
17.
Curr Cardiol Rep ; 21(8): 80, 2019 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-31278490

RESUMEN

PURPOSE OF REVIEW: Interventional cardiology and in particular the field of renal denervation is subject to constant change. This review provides an up to date overview of renal denervation trials and an outlook on what to expect in the future. RECENT FINDINGS: After the sham-controlled SYMPLICITY HTN-3 trial dampened the euphoria following early renal denervation trials, the recently published results of the sham-controlled SPYRAL HTN and RADIANCE HTN trials provided proof-of-principle for the blood pressure-lowering efficacy of renal denervation. However, these studies underline the major issue of patients' non-adherence to antihypertensive medication as well as the need for reliable patient- and procedure-related predictors of response. The second generation of sham-controlled renal denervation trials provided proof of principle for the blood pressure-lowering efficacy of RDN. However, larger trials have to assess long-term safety and efficacy.


Asunto(s)
Presión Sanguínea/fisiología , Desnervación , Hipertensión/cirugía , Riñón/fisiopatología , Arteria Renal/cirugía , Simpatectomía , Antihipertensivos , Humanos , Hipertensión/fisiopatología , Arteria Renal/inervación
19.
J Am Coll Cardiol ; 73(23): 3006-3017, 2019 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-31196459

RESUMEN

Three recent renal denervation studies in both drug-naïve and drug-treated hypertensive patients demonstrated a significant reduction of ambulatory blood pressure compared with respective sham control groups. Improved trial design, selection of relevant patient cohorts, and optimized interventional procedures have likely contributed to these positive findings. However, substantial variability in the blood pressure response to renal denervation can still be observed and remains a challenging and important problem. The International Sympathetic Nervous System Summit was convened to bring together experts in both experimental and clinical medicine to discuss the current evidence base, novel developments in our understanding of neural interplay, procedural aspects, monitoring of technical success, and others. Identification of relevant trends in the field and initiation of tailored and combined experimental and clinical research efforts will help to address remaining questions and provide much-needed evidence to guide clinical use of renal denervation for hypertension treatment and other potential indications.


Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial/tendencias , Congresos como Asunto/tendencias , Hipertensión/cirugía , Internacionalidad , Riñón/inervación , Simpatectomía/tendencias , Presión Sanguínea/fisiología , Desnervación/métodos , Desnervación/tendencias , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Riñón/fisiología , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Literatura de Revisión como Asunto , Simpatectomía/métodos , Sistema Nervioso Simpático/fisiología , Sistema Nervioso Simpático/fisiopatología
20.
Rev Cardiovasc Med ; 20(1): 9-18, 2019 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-31184091

RESUMEN

Hypertension remains a major public health problem and one of the most relevant causes of cardiovascular mortality and morbidity worldwide. Roughly 10% of hypertensive individuals are considered as "resistant" as they are not able to achieve and maintain optimal blood pressure values despite the concurrent use of 3 antihypertensive agents of different classes at optimal doses. As resistant hypertension conveys a higher risk of adverse outcomes, the search for effective treatments to properly manage this condition has progressively surged as a true health priority. The renal nerve plexus plays a central role in regulating arterial blood pressure and renal sympathetic overactivity is a major component in the development and progression of hypertension. On these premises, minimally-invasive catheter based devices for renal nerve ablation have been developed and tested as an alternative treatment for resistant hypertension, but clinical study results have been ambiguous. This review provides a historical perspective on the scientific evidence forming the foundation of renal never ablation from accrued clinical evidence to possible future applications, reaching a tentative conclusion that more research and clinical experience is needed to fully reveal limits and potential indications of this procedure.


Asunto(s)
Presión Sanguínea , Ablación por Catéter , Hipertensión/cirugía , Riñón/irrigación sanguínea , Arteria Renal/inervación , Simpatectomía/métodos , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Ensayos Clínicos como Asunto , Resistencia a Medicamentos , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Simpatectomía/efectos adversos , Resultado del Tratamiento
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