...ambulatory blood pressure is the state-of-the-art technique for measuring blood pressure in patients with treatment-resistant hypertension.2 Poor drug adherence is common in treatment-resistant ...hypertension,3 but this was not monitored in SYMPLICITY HTN-2, making the study susceptible to the Hawthorne effect.4 The SYMPLICITY HTN-3 trial5 included a sham control and ambulatory blood pressure measurement to balance out the Hawthorne effect, as well as other patient and investigator unspecific effects, and the blood pressure lowering effect of renal denervation was not significant in this trial. ...the meta-analyses showed that renal denervation did not lead to severe adverse events and could be considered safe.6,7 Third, the evidence for the role of the sympathetic system in the pathophysiology of hypertension is strong.8,9 Finally, the clinical problems that interfered with renal denervation could be overcome.10,11 However, because of the clinical problems and findings of the meta-analyses, actually showing a blood pressure lowering effect of renal denervation seemed like an uphill battle. Future research also needs to confirm whether there is a sustained blood pressure lowering effect, which could then be cost-effective,16 and whether the procedure is safe in the long term, beyond the initial 6 months.6,7 Additionally, future research will need to show whether the blood pressure reduction caused by renal denervation has protective effects on the brain, heart, kidneys, and large arteries, and, eventually, whether it lowers cardiovascular morbidity and mortality.
Pseudopheochromocytoma Mamilla, Divya; Gonzales, Melissa K; Esler, Murray D ...
Endocrinology and metabolism clinics of North America,
12/2019, Letnik:
48, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Pseudopheochromocytoma manifests as severe, symptomatic paroxysmal hypertension without significant elevation in catecholamine and metanephrine levels and lack of evidence of tumor in the adrenal ...gland. The clinical manifestations are similar but not identical to those in excess circulating catecholamines. The underlying symptomatic mechanism includes augmented cardiovascular responsiveness to catecholamines alongside heightened sympathetic nervous stimulation. The psychological characteristics are probably attributed to the component of repressed emotions related to a past traumatic episode or repressive coping style. Successful management can be achieved by strong collaboration between a hypertension specialist and a psychiatrist or psychologist with expertise in cognitive-behavioral panic management.
Sympathetic stimulation induces left ventricular hypertrophy and is associated with increased cardiovascular risk. Catheter-based renal denervation (RDN) has been shown to reduce sympathetic outflow ...and blood pressure (BP). The present multi-centre study aimed to investigate the effect of RDN on anatomic and functional myocardial parameters, assessed by cardiac magnetic resonance (CMR), in patients with resistant hypertension.
Cardiac magnetic resonance was performed in 72 patients (mean age 66 ± 10 years) with resistant hypertension (55 patients underwent RDN, 17 served as controls) at baseline and after 6 months. Clinical data and CMR results were analysed blindly. Renal denervation significantly reduced systolic and diastolic BP by 22/8 mm Hg and left ventricular mass index (LVMI) by 7.1% (46.3 ± 13.6 g/m(1.7) vs. 43.0 ± 12.6 g/m(1.7), P < 0.001) without changes in the control group (41.9 ± 10.8 g/m(1.7) vs. 42.0 ± 9.7 g/m(1.7), P = 0.653). Ejection fraction (LVEF) in patients with impaired LVEF at baseline (<50%) significantly increased after RDN (43% vs. 50%, P < 0.001). Left ventricular circumferential strain as a surrogate of diastolic function in the subgroup of patients with reduced strain at baseline increased by 21% only in the RDN group (-14.8 vs. -17.9; P = 0.001) and not in control patients (-15.5 vs. -16.4, P = 0.508).
Catheter-based RDN significantly reduced BP and LVMI and improved EF and circumferential strain in patients with resistant hypertension, occurring partly BP independently.
Polycystic ovary syndrome (PCOS) is associated with sympathetic nervous system activation, insulin resistance, and blood pressure elevation. Renal nerve ablation has been demonstrated to reduce ...sympathetic outflow and improve blood pressure control. Here we report on the effects of renal denervation on hemodynamic, metabolic, and renal parameters in two obese PCOS patients with hypertension.
Sympathetic nerve activity was assessed at baseline using microneurography and norepinephrine spillover measurements. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp. Measurements of cystatin-C, creatinine clearance, and urinary albumin-creatinine ratio were also obtained. All measurements were repeated 3 months after bilateral renal denervation achieved via percutaneous endovascular radiofrequency ablation.
Muscle sympathetic nerve activity and whole body norepinephrine spillover were substantially elevated at baseline in both patients by approximately 2.5-3-fold. Bilateral renal nerve ablation reduced both indices of sympathetic nerve activity. This was associated with moderate reductions in blood pressure and a substantial improvement in insulin sensitivity by approximately 17.5% in the absence of weight changes at 3-month follow-up. Glomerular hyperfiltration and urinary albumin excretion were also reduced.
These findings corroborate the relevance of sympathetic activation in PCOS and suggest that renal denervation exerts beneficial effects not only on blood pressure control but also on insulin sensitivity, renal, and endocrine abnormalities characteristic of PCOS.
SNS (sympathetic nervous system) activation is a common feature of arterial hypertension and has been demonstrated to contribute to the development and progression of the hypertensive state. ...Persuasive evidence suggests a strong association between SNS overactivity and variety of disease states, including chronic renal failure, insulin resistance, congestive heart failure, sleep apnoea, ventricular arrhythmias and others. Although sympatholytic agents are available to target SNS overactivity pharmacologically, they are not widely used in clinical practice, leaving the SNS unopposed in many patients. The recent introduction of catheter-based renal denervation as an alternative approach to target the SNS therapeutically has been demonstrated to result in a clinically relevant blood pressure reduction in patients with resistant hypertension, presumably through its effects on both efferent and afferent renal nerve traffic. Available data on this interventional procedure demonstrate a favourable vascular and renal safety profile. Preliminary data obtained primarily from small and mostly uncontrolled studies in related disease states often characterized by overactivity of the SNS are promising, but require confirmation in appropriately designed clinical trials. In the present paper, we briefly review the physiology of the renal nerves and their role in hypertension and other relevant disease states, summarize the data currently available from clinical studies pertaining to the safety and efficacy of renal denervation in resistant hypertension, discuss potential future implications and the available data supporting such a role for renal denervation, and describe some of the newer devices currently under investigation to achieve improved blood pressure control via renal denervation.
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.
Left ventricular (LV) hypertrophy is an independent risk factor for cardiovascular morbidity and mortality in hypertensive subjects. Sympathetic activation has been suggested to contribute to LV ...hypertrophy, but this has not yet been conclusively validated in humans.
We comprehensively assessed total systemic and regional sympathetic activity by radiotracer dilution methods and microneurography in 15 untreated hypertensive subjects with echocardiographic evidence of LV hypertrophy (EH+), 11 hypertensive subjects with similar blood pressure but without LV hypertrophy (EH-), and 10 age-matched normotensive control subjects (NT). LV mass index was 87+/-15 g/m2 in NT, 106+/-11 g/m2 in EH-, and 138+/-17 g/m2 in EH+ (P<0.001). Total body and renal norepinephrine spillover were higher in both hypertensive groups compared with NT (total norepinephrine spillover, NT 223+/-145 versus EH- 418+/-135 versus EH+ 497+/-303 ng/min; renal norepinephrine spillover, NT 38.8+/-25.3 versus EH- 88.6+/-58.0 versus EH+ 103.4+/-56.2 ng/min; both P<0.05). However, muscle sympathetic nerve activity (NT 25+/-6 versus EH- 38+/-20 versus EH+ 57+/-19 bursts per 100 heartbeats; P<0.01) and cardiac norepinephrine spillover (NT 11.7+/-6.2 versus EH- 13.1+/-7.2 versus EH+ 28.6+/-17.4 ng/min; P<0.01) were only increased in EH+. Cardiac norepinephrine spillover correlated positively with LV mass index in all subjects (r=0.52; P<0.001).
Our findings demonstrate that hypertensive LV hypertrophy is associated with increased sympathetic activity largely confined to the heart, suggesting that increased cardiac norepinephrine release is related to the development of LV hypertrophy.
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