Renal Sympathetic Denervation for the Treatment of Difficult-to-Control or Resistant Hypertension

Hypertension represents a major health problem with an appalling annual toll. Despite the plethora of antihypertensive drugs, hypertension remains resistant in a considerable number of patients, thus creating the need for alternative strategies, including interventional approaches. Recently, catheter-based renal sympathetic denervation has been shown to be fairly safe and effective in patients with resistant hypertension. Pathophysiology of kidney function, interaction and crosstalk between the kidney and the brain, justifies the use of renal sympathetic denervation in the treatment of hypertension. Data from older studies have shown that sympathectomy has effectively lowered blood pressure and prolonged life expectancy of hypertensive patients, but at considerable cost. Renal sympathetic denervation is devoid of the adverse effects of surgical sympathectomy, due to its localized nature, is minimally invasive, and provides short procedural and recovery times. This paper outlines the pathophysiological background for renal sympathetic denervation, describes the past and the present of this interventional approach, and considers several future potential applications

Executive summary of the joint position paper on renal denervation of the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) and the European Society of Hypertension (ESH)

No abstract available

Time in Therapeutic Range, as a Determinant of All-Cause Mortality in Patients With Hypertension.

BACKGROUND: Accumulating evidence indicates that reducing systolic blood pressure (BP) tooutcomes; however, an optimal level has not yet been determined. Many population studies or post hoc analyses suggest a target systolic BP between 120 and 140 mm Hg with increased risk above and below that range. We tested the hypothesis that consistent control of systolic BP between 120 and 140 mm Hg-time in therapeutic range-is a strong determinant of all-cause mortality among US veterans. METHODS AND RESULTS: A total of 689 051 individuals from 15 Veterans Administration Medical Centers were followed over a 10-year period. Participants were classified as hypertensive, intermediate hypertensive, and normotensive according to the number of elevated BP recordings (\u3e3, 1 or 2, and none, respectively). Time within, above, or below therapeutic range (120-140 mm Hg) was considered in quartiles and related to all-cause mortality. The study population consisted of 54% hypertensive, 19.9% intermediate, and 26.1% normotensive participants; the corresponding mortality rates for the 3 groups were 11.5%, 8%, and 1.9%, respectively (P75%) to 8.9%, 15.6%, and 23.5% towards the less consistently controlled quartiles (50-75%, 25-50%, and CONCLUSIONS: An inverse and gradual association between time in therapeutic range and all-cause mortality was observed in this large veteran cohort. Consistency of BP control over time is a strong determinant of all-cause mortality, and consistency of BP control should be monitored in everyday clinical practice

Implementing the Proclamation of Stroke and Potentially Preventable Dementias

Brain health plays a central role in wellbeing and in the management of chronic diseases. Stroke and dementia pose the two greatest threats to brain health, but recent developments suggest the possibility that preventing stroke may also prevent some dementias: 1. A large population study showed a 32% decrease in the incidence of stroke and a concomitant 7% reduction in the incidence of dementia; 2. Treatment of atrial fibrillation resulted not only in stroke reduction, but a 48% decrease in dementia; 3. A hypothesis free analyses has shown that the first phase of Alzheimer disease involves vascular dysregulation, opening the door to new therapeutic approaches; 4. Cognitive impairment, often treatable and reversible, accompanies heart and kidney failure. These developments, combined with the knowledge that stroke, dementia and heart disease share the same major treatable risk factors, particularly hypertension, offers an opportunity for their joint prevention. This aspiration is expressed by a Proclamation of the World Stroke Organization on Stroke and Potentially Preventable Dementias and endorsed by the World Heart Federation, the World Hypertension League, Alzheimer Disease International and 18 other international, regional and national organizations as a call for action

Pathophysiology of Resistant Hypertension: The Role of Sympathetic Nervous System

Resistant hypertension (RH) is a powerful risk factor for cardiovascular morbidity and mortality. Among the characteristics of patients with RH, obesity, obstructive sleep apnea, and aldosterone excess are covering a great area of the mosaic of RH phenotype. Increased sympathetic nervous system (SNS) activity is present in all these underlying conditions, supporting its crucial role in the pathophysiology of antihypertensive treatment resistance. Current clinical and experimental knowledge points towards an impact of several factors on SNS activation, namely, insulin resistance, adipokines, endothelial dysfunction, cyclic intermittent hypoxaemia, aldosterone effects on central nervous system, chemoreceptors, and baroreceptors dysregulation. The further investigation and understanding of the mechanisms leading to SNS activation could reveal novel therapeutic targets and expand our treatment options in the challenging management of RH

The relationship between blood pressure and risk of atrial fibrillation: a Mendelian randomization study

AIMS: Observational studies suggest elevated blood pressure (BP) as the leading risk factor for incident atrial fibrillation (AF), but whether this relationship is causal remains unknown. In this study, we used Mendelian randomization (MR) to investigate the potential causal association of BP levels with the risk of developing AF.METHODS AND RESULTS: Genetic variants associated with the BP traits were retrieved from the International Consortium of Blood Pressure-Genome Wide Association Studies (N=299024). From 901 reported variants, 894 were assessed in a dedicated Genome-Wide Association Study of AF genetics, including >1000000 subjects of European ancestry. We used two-sample MR analyses to examine the potential causal association of systolic BP (SBP) and diastolic BP (DBP) as well as of pulse pressure (PP) with AF. MR analysis identified a potentially causal association between AF and SBP [odds ratio (OR): 1.018 per 1mmHg increase, 95% confidence interval (CI): 1.012-1.024, P<0.001], DBP (OR: 1.026, 95% CI: 1.016-1.035, P<0.001), and PP (OR: 1.014, 95% CI: 1.001-1.028, P=0.033). These findings were robust in sensitivity analyses, including the MR-Egger method and the MR pleiotropy residual sum and outlier test (MR-PRESSO). The causal relationship of BP and AF did not change when single-nucleotide polymorphisms associated with possible confounders (i.e. coronary artery disease and obesity) of the causal relationship were excluded.CONCLUSIONS: The association between increased BP levels and the risk of AF is likely causal and applies for different BP indices. Independently from other risk factors, optimal BP control might represent an important therapeutic target for AF prevention in the general population

Carotid Baroreceptor Stimulation for the Treatment of Resistant Hypertension

Interventional activation of the carotid baroreflex has been an appealing idea for the management of resistant hypertension for several decades, yet its clinical application remained elusive and a goal for the future. It is only recently that the profound understanding of the complex anatomy and pathophysiology of the circuit, combined with the accumulation of relevant experimental and clinical data both in animals and in humans, has allowed the development of a more effective and well-promising approach. Indeed, current data support a sustained over a transient reduction of blood pressure through the resetting of baroreceptors, and technical deficits have been minimized with a subsequent recession of adverse events. In addition, clinical outcomes from the application of a new implantable device (Rheos) that induces carotid baroreceptor stimulation point towards a safe and effective blood pressure reduction, but longer experience is needed before its integration in the everyday clinical practice. While accumulating evidence indicates that carotid baroreceptor stimulation exerts its benefits beyond blood pressure reduction, further research is necessary to assess the spectrum of beneficial effects and evaluate potential hazards, before the extraction of secure conclusions

Safety and efficacy of a multi-electrode renal sympathetic denervation system in resistant hypertension: The EnligHTN I trial

Aims: Catheter-based renal artery sympathetic denervation has emerged as a novel therapy for treatment of patients with drug-resistant hypertension. Initial studies were performed using a single electrode radiofrequency catheter, but recent advances in catheter design have allowed the development of multi-electrode systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and efficacy of the EnligHTN™ multi-electrode system. Methods and results: We conducted the first-in-human, prospective, multi-centre, non-randomized study in 46 patients (67% male, mean age 60 years, and mean baseline office blood pressure 176/96 mmHg) with drug-resistant hypertension. The primary efficacy objective was change in office blood pressure from baseline to 6 months. Safety measures included all adverse events with a focus on the renal artery and other vascular complications and changes in renal function. Renal artery denervation, using the EnligHTN™ system significantly reduced the office blood pressure from baseline to 1, 3, and 6 months by −28/10, −27/10 and −26/10 mmHg, respectively (P < 0.0001). No acute renal artery injury or other serious vascular complications occurred. Small, non-clinically relevant, changes in average estimated glomerular filtration rate were reported from baseline (87 ± 19 mL/min/1.73 m2) to 6 months post-procedure (82 ± 20 mL/min/1.73 m2). Conclusion: Renal sympathetic denervation, using the EnligHTN™ multi-electrode catheter results in a rapid and significant office blood pressure reduction that was sustained through 6 months. The EnligHTN™ system delivers a promising therapy for the treatment of drug-resistant hypertension.Stephen G. Worthley, Costas P. Tsioufis, Matthew I. Worthley, Ajay Sinhal, Derek P. Chew, Ian T. Meredith, Yuvi Malaiapan, and Vasilios Papademetrio

Hypertension: Renal Denervation: Hype After Initial Hope/Lessons to be Learned From its Fall/Other Methods Influencing the Autonomic Nervous System

The unexpected announcement of Symplicity HTN-3 trial by the sponsor company that renal sympathetic denervation (RDN) failed to meet its primary efficacy end-point at 6 months raised concerns regarding the extent of blood pressure (BP) lowering results of the procedure.1 But the answer to the “burning” question of whether we should stop research and clinical implementation of RDN based on the results of one trial needs a cautious approach