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Background-Hypertension is associated with impaired glucose metabolism and insulin resistance. Chronic activation of the sympathetic nervous system may contribute to either condition. We investigated the effect of catheter-based renal sympathetic denervation on glucose metabolism and blood pressure control in patients with resistant hypertension. Methods and Results-We enrolled 50 patients with therapy-resistant hypertension. Thirty-seven patients underwent bilateral catheter-based renal denervation, and 13 patients were assigned to a control group. Systolic and diastolic blood pressures, fasting glucose, insulin, C peptide, hemoglobin A 1c , calculated insulin sensitivity (homeostasis model assessment-insulin resistance), and glucose levels during oral glucose tolerance test were measured before and 1 and 3 months after treatment. Mean office blood pressure at baseline was 178/96Ϯ3/2 mm Hg. At 1 and 3 months, office blood pressure was reduced by Ϫ28/Ϫ10 mm Hg (PϽ0.001) and Ϫ32/Ϫ12 mm Hg (PϽ0.001), respectively, in the treatment group, without changes in concurrent antihypertensive treatment. Three months after renal denervation, fasting glucose was reduced from 118Ϯ3.4 to 108Ϯ3.8 mg/dL (Pϭ0.039). Insulin levels were decreased from 20.8Ϯ3.0 to 9.3Ϯ2.5 IU/mL (Pϭ0.006) and C-peptide levels from 5.3Ϯ0.6 to 3.0Ϯ0.9 ng/mL (Pϭ0.002). After 3 months, homeostasis model assessment-insulin resistance decreased from 6.0Ϯ0.9 to 2.4Ϯ0.8 (Pϭ0.001). Additionally, mean 2-hour glucose levels during oral glucose tolerance test were reduced significantly by 27 mg/dL (Pϭ0.012). There were no significant changes in blood pressure or metabolic markers in the control group. Conclusions-Renal denervation improves glucose metabolism and insulin sensitivity in addition to a significantly reducing blood pressure. However, this improvement appeared to be unrelated to changes in drug treatment. This novel procedure may therefore provide protection in patients with resistant hypertension and metabolic disorders at high cardiovascular risk. Clinical Trial Registration-URL: http://www.ClinicalTrials.gov. Unique identifiers: NCT00664638 and NCT00888433.

Besides the known effect on blood pressure, our study showed for the first time that RD significantly reduces LV mass and improves diastolic function, which might have important prognostic implications in patients with resistant hypertension at high cardiovascular risk.

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RDN reduced office BP and improved relevant aspects of ambulatory BP monitoring, commonly linked to high cardiovascular risk, in patients with true-treatment resistant hypertension, whereas it only affected office BP in pseudoresistant hypertension.

AimsFunctional mitral regurgitation (FMR) contributes to morbidity and mortality in heart failure (HF) patients. The aim of this study was to determine whether percutaneous mitral annuloplasty could safely and effectively reduce FMR and yield durable long-term clinical benefit.Methods and resultsThe impact of mitral annuloplasty (Carillon Mitral Contour System) was evaluated in HF patients with at least moderate FMR. Patients in whom the device was placed then acutely recaptured for clinical reasons served as a comparator group. Quantitative measures of FMR, left ventricular (LV) dimensions, New York Heart Association (NYHA) class, 6 min walk distance (6MWD), and quality of life were assessed in both groups up to 12 months. Safety and key functional data were assessed in the implanted cohort up to 24 months. Thirty-six patients received a permanent implant; 17 had the device recaptured. The 30-day major adverse event rate was 1.9%. In contrast to the comparison group, the implanted cohort demonstrated significant reductions in FMR as represented by regurgitant volume [baseline 34.5 ±11.5 mL to 17.4 ±12.4 mL at 12 months (P < 0.001)]. There was a corresponding reduction in LV diastolic volume [baseline 208.5 ±62.0 mL to 178.9 ±48.0 mL at 12 months (P =0.015)] and systolic volume [baseline 151.8 ±57.1 mL to 120.7 ±43.2 mL at 12 months (P =0.015)], compared with progressive LV dilation in the comparator. The 6MWD markedly improved for the implanted patients by 102.5 ±164 m at 12 months (P =0.014) and 131.9 ±80 m at 24 months (P < 0.001).ConclusionPercutaneous reduction of FMR using a coronary sinus approach is associated with reverse LV remodelling. Significant clinical improvements persisted up to 24 months.

Background— Impairment of intracellular Ca 2+ homeostasis and mitochondrial function has been implicated in the development of cardiomyopathy. Mitochondrial Ca 2+ uptake is thought to be mediated by the Ca 2+ uniporter (MCU) and a thus far speculative non-MCU pathway. However, the identity and properties of these pathways are a matter of intense debate, and possible functional alterations in diseased states have remained elusive. Methods and Results— By patch clamping the inner membrane of mitochondria from nonfailing and failing human hearts, we have identified 2 previously unknown Ca 2+ -selective channels, referred to as mCa1 and mCa2. Both channels are voltage dependent but differ significantly in gating parameters. Compared with mCa2 channels, mCa1 channels exhibit a higher single-channel amplitude, shorter openings, a lower open probability, and 3 to 5 subconductance states. Similar to the MCU, mCa1 is inhibited by 200 nmol/L ruthenium 360, whereas mCa2 is insensitive to 200 nmol/L ruthenium 360 and reduced only by very high concentrations (10 μmol/L). Both mitochondrial Ca 2+ channels are unaffected by blockers of other possibly Ca 2+ -conducting mitochondrial pores but were activated by spermine (1 mmol/L). Notably, activity of mCa1 and mCa2 channels is decreased in failing compared with nonfailing heart conditions, making them less effective for Ca 2+ uptake and likely Ca 2+ -induced metabolism. Conclusions— Thus, we conclude that the human mitochondrial Ca 2+ uptake is mediated by these 2 distinct Ca 2+ channels, which are functionally impaired in heart failure. Current properties reveal that the mCa1 channel underlies the human MCU and that the mCa2 channel is responsible for the ruthenium red–insensitive/low-sensitivity non-MCU–type mitochondrial Ca 2+ uptake.