Michael Uder

Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial.

BACKGROUND Activation of renal sympathetic nerves is key to pathogenesis of essential hypertension. We aimed to assess effectiveness and safety of catheter-based renal denervation for reduction of blood pressure in patients with treatment-resistant hypertension. METHODS In this multicentre, prospective, randomised trial, patients who had a baseline systolic blood pressure of 160 mm Hg or more (≥150 mm Hg for patients with type 2 diabetes), despite taking three or more antihypertensive drugs, were randomly allocated in a one-to-one ratio to undergo renal denervation with previous treatment or to maintain previous treatment alone (control group) at 24 participating centres. Randomisation was done with sealed envelopes. Data analysers were not masked to treatment assignment. The primary effectiveness endpoint was change in seated office-based measurement of systolic blood pressure at 6 months. Primary analysis included all patients remaining in follow-up at 6 months. This trial is registered with ClinicalTrials.gov, number NCT00888433. FINDINGS 106 (56%) of 190 patients screened for eligibility were randomly allocated to renal denervation (n=52) or control (n=54) groups between June 9, 2009, and Jan 15, 2010. 49 (94%) of 52 patients who underwent renal denervation and 51 (94%) of 54 controls were assessed for the primary endpoint at 6 months. Office-based blood pressure measurements in the renal denervation group reduced by 32/12 mm Hg (SD 23/11, baseline of 178/96 mm Hg, p<0·0001), whereas they did not differ from baseline in the control group (change of 1/0 mm Hg [21/10], baseline of 178/97 mm Hg, p=0·77 systolic and p=0·83 diastolic). Between-group differences in blood pressure at 6 months were 33/11 mm Hg (p<0·0001). At 6 months, 41 (84%) of 49 patients who underwent renal denervation had a reduction in systolic blood pressure of 10 mm Hg or more, compared with 18 (35%) of 51 controls (p<0·0001). We noted no serious procedure-related or device-related complications and occurrence of adverse events did not differ between groups; one patient who had renal denervation had possible progression of an underlying atherosclerotic lesion, but required no treatment. INTERPRETATION Catheter-based renal denervation can safely be used to substantially reduce blood pressure in treatment-resistant hypertensive patients. FUNDING Ardian.

Nephrotoxicity of Iso-osmolar Iodixanol Compared with Nonionic Low-osmolar Contrast Media: Meta-analysis of Randomized Controlled Trials

PURPOSE To compare the nephrotoxicity of iso-osmolar iodixanol with that of nonionic low-osmolar contrast media (CM) (LOCM) in randomized clinical trials. MATERIALS AND METHODS This meta-analysis was conducted with a systematic search of MEDLINE, EMBASE, BIOSIS, Web of Science, ISI Web of Knowledge, Current Contents Medizin, Cochrane Library (until August 2007), trial registers, conference proceedings, and reference lists to identify studies and with requests from all manufacturers of CM for unidentified studies. Randomized controlled trials assessing serum creatinine levels before and after intravascular application of iodixanol or LOCM were included. The primary outcome measures were the incidence of contrast medium-induced nephropathy (CIN) and change in serum creatinine levels. RESULTS Twenty-five trials were included. Iodixanol did not significantly reduce the risk of CIN (relative risk [RR], 0.80; 95% confidence interval [CI]: 0.61, 1.04; weighted mean difference in serum creatinine increase, 0.01 mg/dL [0.88 mumol/L]; 95% CI: -0.01, 0.03). There was no significant risk reduction after intravenous administration of the CM (RR, 1.08; 95% CI: 0.62, 1.89); subgroup with preexisting renal insufficiency (RR, 1.07; 95% CI: 0.56, 2.02) or after intraarterial administration (RR, 0.68; 95% CI: 0.46, 1.01); subgroup with preexisting renal insufficiency (RR, 0.59; 95% CI: 0.33, 1.07). However, in patients with intraarterial administration and renal insufficiency, the risk of CIN was greater for iohexol than for iodixanol (RR, 0.38; 95% CI: 0.21, 0.68), whereas there was no difference between iodixanol and the other (noniohexol) LOCM (RR, 0.95; 95% CI: 0.50, 1.78). CONCLUSION Iodixanol is not associated with a significantly reduced risk of CIN compared with the LOCM pooled together. However, in patients with intraarterial administration and renal insufficiency, iodixanol is associated with a reduced risk of CIN compared with iohexol, whereas no significant difference between iodixanol and other LOCM could be found.

Detection of Coronary Artery Stenoses by Low-Dose, Prospectively ECG-Triggered, High-Pitch Spiral Coronary CT Angiography

OBJECTIVES We sought to evaluate the diagnostic accuracy of a new prospectively electrocardiogram (ECG)-triggered high-pitch scan mode for coronary computed tomography angiography (CTA), which allows an effective dose of less than 1 mSv. BACKGROUND Coronary CTA provides increasingly reliable image quality, but the associated radiation exposure can be high. METHODS Seventy-five patients with suspected coronary artery disease and in sinus rhythm were screened for participation. After exclusion of 25 patients for body weight >100 kg or failure to lower heart rate to ≤ 60 beats/min, 50 patients were studied by prospectively ECG-triggered high-pitch spiral computed tomography (CT). Coronary CTA was performed using a dual-source CT system with 2 × 128 × 0.6-mm collimation, 0.28-s rotation time, a pitch of 3.4, 100-kVp tube voltage, and current of 320 mA. Data acquisition was prospectively triggered at 60% of the R-R interval and completed within 1 cardiac cycle. Diagnostic accuracy for detection of coronary artery stenoses ≥ 50% diameter stenosis was determined by comparison to invasive coronary angiography. Per-patient diagnostic performance was the primary form of analysis. RESULTS In all 50 patients (34 males, 59 ± 12 years of age), imaging was successful. For the detection of 16 patients with at least 1 coronary artery stenosis, CT demonstrated a sensitivity of 100% (95% confidence interval [CI]: 79% to 100%) and specificity of 82% (95% CI: 65% to 93%). The positive predictive value was 72% (95% CI: 49% to 89%) and the negative predictive value was 100% (95% CI: 87% to 100%). Sensitivity was 100% (95% CI: 88% to 100%) and specificity was 94% (95% CI: 89% to 97%) on a per-vessel basis. Per-segment sensitivity was 92% (95% CI: 80% to 97%), and specificity was 98% (95% CI: 96% to 98%). Mean dose-length product for coronary CTA was 54 ± 6 mGy · cm, the effective dose was 0.76 ± 0.08 mSv (0.64 to 0.95 mSv). CONCLUSIONS In nonobese patients with a low and stable heart rate, prospectively ECG-triggered high-pitch spiral coronary CTA provides high diagnostic accuracy for the detection of coronary artery stenoses.

(23)Na magnetic resonance imaging-determined tissue sodium in healthy subjects and hypertensive patients

High dietary salt intake is associated with hypertension; the prevalence of salt-sensitive hypertension increases with age. We hypothesized that tissue Na+ might accumulate in hypertensive patients and that aging might be accompanied by Na+ deposition in tissue. We implemented 23Na magnetic resonance imaging to measure Na+ content of soft tissues in vivo earlier, but had not studied essential hypertension. We report on a cohort of 56 healthy control men and women, and 57 men and women with essential hypertension. The ages ranged from 22 to 90 years. 23Na magnetic resonance imaging measurements were made at the level of the calf. We observed age-dependent increases in Na+ content in muscle in men, whereas muscle Na+ content did not change with age in women. We estimated water content with conventional MRI and found no age-related increases in muscle water in men, despite remarkable Na+ accumulation, indicating water-free Na+ storage in muscle. With increasing age, there was Na+ deposition in the skin in both women and men; however, skin Na+ content remained lower in women. Similarly, this sex difference was found in skin water content, which was lower in women than in men. In contrast to muscle, increasing Na+ content was paralleled with increasing skin water content. When controlled for age, we found that patients with refractory hypertension had increased tissue Na+ content, compared with normotensive controls. These observations suggest that 23Na magnetic resonance imaging could have utility in assessing the role of tissue Na+ storage for cardiovascular morbidity and mortality in longitudinal studies.

High-pitch spiral computed tomography: effect on image quality and radiation dose in pediatric chest computed tomography.

Objectives:Computed tomography (CT) is considered the method of choice in thoracic imaging for a variety of indications. Sedation is usually necessary to enable CT and to avoid deterioration of image quality because of patient movement in small children. We evaluated a new, subsecond high-pitch scan mode (HPM), which obviates the need of sedation and to hold the breath. Material and Methods:A total of 60 patients were included in this study. 30 patients (mean age, 14 ± 17 month; range, 0–55 month) were examined with a dual source CT system in an HPM. Scan parameters were as follows: pitch = 3.0, 128 × 0.6 mm slice acquisition, 0.28 seconds gantry rotation time, ref. mAs adapted to the body weight (50–100 mAs) at 80 kV. Images were reconstructed with a slice thickness of 0.75 mm. None of the children was sedated for the CT examination and no breathing instructions were given. Image quality was assessed focusing on motion artifacts and delineation of the vascular structures and lung parenchyma. Thirty patients (mean age, 15 ± 17 month; range, 0–55 month) were examined under sedation on 2 different CT systems (10-slice CT, n = 18; 64-slice CT, n = 13 patients) in conventional pitch mode (CPM). Dose values were calculated from the dose length product provided in the patient protocol/dose reports, Monte Carlo simulations were performed to assess dose distribution for CPM and HPM. Results:All scans were performed without complications. Image quality was superior with HPM, because of a significant reduction in motion artifacts, as compared to CPM with 10- and 64-slice CT. In the control group, artifacts were encountered at the level of the diaphragm (n = 30; 100%), the borders of the heart (n = 30; 100%), and the ribs (n = 20; 67%) and spine (n = 6; 20%), whereas motion artifacts were detected in the HPM-group only in 6 patients in the lung parenchyma next to the diaphragm or the heart (P < 0,001). Dose values were within the same range in the patient examinations (CPM, 1.9 ± 0.6 mSv; HPM, 1.9 ± 0.5 mSv; P = 0.95), although z-overscanning increased with the increase of detector width and pitch-value. Conclusion:High-pitch chest CT is a robust method to provide highest image quality making sedation or controlled ventilation for the examination of infants, small or uncooperative children unnecessary, whereas maintaining low radiation dose values.

Dose reduction in abdominal computed tomography: intraindividual comparison of image quality of full-dose standard and half-dose iterative reconstructions with dual-source computed tomography.

Objectives:We sought to evaluate the image quality of iterative reconstruction in image space (IRIS) in half-dose (HD) datasets compared with full-dose (FD) and HD filtered back projection (FBP) reconstruction in abdominal computed tomography (CT). Materials and Methods:To acquire data with FD and HD simultaneously, contrast-enhanced abdominal CT was performed with a dual-source CT system, both tubes operating at 120 kV, 100 ref.mAs, and pitch 0.8. Three different image datasets were reconstructed from the raw data: Standard FD images applying FBP which served as reference, HD images applying FBP and HD images applying IRIS. For the HD data sets, only data from 1 tube detector-system was used. Quantitative image quality analysis was performed by measuring image noise in tissue and air. Qualitative image quality was evaluated according to the European Guidelines on Quality criteria for CT. Additional assessment of artifacts, lesion conspicuity, and edge sharpness was performed. Results:Image noise in soft tissue was substantially decreased in HD-IRIS (−3.4 HU, −22%) and increased in HD-FBP (+6.2 HU, +39%) images when compared with the reference (mean noise, 15.9 HU). No significant differences between the FD-FBP and HD-IRIS images were found for the visually sharp anatomic reproduction, overall diagnostic acceptability (P = 0.923), lesion conspicuity (P = 0.592), and edge sharpness (P = 0.589), while HD-FBP was rated inferior. Streak artifacts and beam hardening was significantly more prominent in HD-FBP while HD-IRIS images exhibited a slightly different noise pattern. Conclusions:Direct intrapatient comparison of standard FD body protocols and HD-IRIS reconstruction suggest that the latest iterative reconstruction algorithms allow for approximately 50% dose reduction without deterioration of the high image quality necessary for confident diagnosis.

Cutaneous Na+ Storage Strengthens the Antimicrobial Barrier Function of the Skin and Boosts Macrophage-Driven Host Defense

Immune cells regulate a hypertonic microenvironment in the skin; however, the biological advantage of increased skin Na(+) concentrations is unknown. We found that Na(+) accumulated at the site of bacterial skin infections in humans and in mice. We used the protozoan parasite Leishmania major as a model of skin-prone macrophage infection to test the hypothesis that skin-Na(+) storage facilitates antimicrobial host defense. Activation of macrophages in the presence of high NaCl concentrations modified epigenetic markers and enhanced p38 mitogen-activated protein kinase (p38/MAPK)-dependent nuclear factor of activated T cells 5 (NFAT5) activation. This high-salt response resulted in elevated type-2 nitric oxide synthase (Nos2)-dependent NO production and improved Leishmania major control. Finally, we found that increasing Na(+) content in the skin by a high-salt diet boosted activation of macrophages in a Nfat5-dependent manner and promoted cutaneous antimicrobial defense. We suggest that the hypertonic microenvironment could serve as a barrier to infection.

Renal Denervation in Moderate Treatment-Resistant Hypertension

OBJECTIVES This study sought to investigate the effect of renal denervation (RDN) in patients with treatment-resistant hypertension according to the established definition (Joint National Committee VII and European Society of Hypertension/European Society of Cardiology guidelines), that is, office blood pressure (BP) ≥140/90 mm Hg (with at least three antihypertensive drugs, including a diuretic, in adequate doses) and confirmed by 24-h ambulatory BP monitoring (ABPM). BACKGROUND RDN emerged as an innovative interventional antihypertensive therapy. However, so far, only patients with severe hypertension (systolic BP ≥160 mm Hg or ≥150 mm Hg for patients with type 2 diabetes) have been investigated. METHODS In this study, there were 54 patients with moderate treatment-resistant hypertension (office BP ≥140/90 mm Hg and <160/100 mm Hg and diagnosis confirmed by 24-h ABPM of ≥130/80 mm Hg) who underwent catheter-based RDN using the Symplicity catheter (Medtronic Inc., Mountain View, California). RESULTS Patients were treated with 5.1 ± 1.4 antihypertensive drugs on average. Office BP was significantly reduced by 13/7 mm Hg 6 months after RDN (systolic: 151 ± 6 mm Hg vs. 138 ± 21 mm Hg, p < 0.001; diastolic: 83 ± 11 mm Hg vs. 75 ± 11 mm Hg, p < 0.001). In patients (n = 36) who underwent ABPM 6 months after treatment, there was a reduction in average 24-h ABPM by 14/7 mm Hg (systolic: 150 ± 16 mm Hg vs. 136 ± 16 mm Hg, p < 0.001; diastolic: 83 ± 10 mm Hg vs. 76 ± 10 mm Hg, p < 0.001). In 51% of patients, office BP was controlled below 140/90 mm Hg after RDN. In addition, heart rate decreased from 67 ± 11 to 63 ± 10 beats/min (p = 0.006). CONCLUSIONS Our data indicate that RDN may reduce office and 24-h ambulatory BP substantially in patients with moderate treatment-resistant hypertension. (Renal Denervation in Treatment Resistant Hypertension; NCT01687725).

23Na Magnetic Resonance Imaging of Tissue Sodium

Hypertension is linked to disturbed total-body sodium (Na+) regulation; however, measuring Na+ disposition in the body is difficult. We implemented 23Na magnetic resonance spectroscopy (23Na-MR) and imaging technique (23Na-MRI) at 9.4T for animals and 3T for humans to quantify Na+ content in skeletal muscle and skin. We compared 23Na-MRI data with actual tissue Na+ content measured by chemical analysis in animal and human tissue. We then quantified tissue Na+ content in normal humans and in patients with primary aldosteronism. We found a 29% increase in muscle Na+ content in patients with aldosteronism compared with normal women and men. This tissue Na+ was mobilized after successful treatment without accompanying weight loss. We suggest that, after further refinements, this tool could facilitate understanding the relationships between Na+ accumulation and hypertension. Furthermore, with additional technical advances, a future clinical use may be possible.

Integrated whole-body PET/MR hybrid imaging: clinical experience.

ObjectivesIntegrated whole-body positron emission tomography (PET)/magnetic resonance (MR) scanners have recently been introduced and potentially offer new possibilities in hybrid imaging of oncologic patients. Integration of PET in a whole-body MR system requires new PET detector technology and new approaches to attenuation correction of PET data based on MR imaging. The aim of this study was to evaluate the clinical performance and image quality parameters of integrated whole-body PET/MR hybrid imaging in intraindividual comparison with PET/CT in oncologic patients. Materials and MethodsEighty patients underwent a single-injection, dual-imaging protocol including whole-body PET/computed tomography (CT) and subsequent whole-body PET/MR hybrid imaging. Positron emission tomography/computed tomography was performed after adequate resting time (73 ± 13 minutes post injectionem of 227 ± 52.7 MBq Fluor-18-Fluordesoxyglucose, 3 minutes of acquisition time for each of 7 bed positions), followed by PET/MR (172 ± 33 minutes post injectionem, 10 minutes acquisition time for each of 4 bed positions). Positron emission tomographic data for both modalities were reconstructed iteratively. Two observers evaluated the following parameters: qualitative correlation of tracer-avid lesions in PET/CT versus PET/MR and PET image quality of PET/CT versus PET/MR. Magnetic resonance image quality of standard sequences (T1-weighted, T2-weighted), performance of the Dixon sequence for MR-based attenuation correction in comparison with corresponding T1-weighted images, artifacts in PET/MR data, and spatial coregistration of PET and MR data were evaluated by another observer. ResultsIn 70 of the 80 patients, both image data sets were complete. In these patients, 192 tracer-avid lesions were identified on PET/CT; 195, on PET/MR. A total of 187 lesions were identified concordantly by both modalities, and this corresponds to an agreement rate of 97.4%. The overall PET image quality was rated good to excellent for PET from PET/CT (12/28, excellent, 42.9%; 16/28, good, 57.1%; 0/28, poor, 0.0%) and slightly superior compared with PET from PET/MR, which was rated good (3/28, excellent, 10.7%; 20/28, good, 71.4%; 5/28, poor, 17.9%) in a subset of 28 patients. The overall image quality of the MR image data sets in all 70 of the 80 patients was rated excellent (260/280, excellent, 92.8%; 15/280, good, 5.4%; 5/280, poor, 1.8%). The Dixon sequence and conversion to &mgr;-maps for MR-based attenuation correction provided robust tissue segmentation in all 280 bed positions of the acquired PET/MR data. No artifacts such as elevated noise and radiofrequency disturbances related to hardware cross talk between the PET and MR components in the hybrid system could be detected in the MR images. Nomajor spatial mismatches between PET and MR data were detected. ConclusionsIntegrated PET/MR hybrid imaging is feasible in a clinical setting with similar detection rates as those of PET/CT. Attenuation correction can be performed sufficiently with Dixon sequences, although bone is disregarded. The administration of specific radiotracers and dedicated imaging sequences will foster this hybrid imaging modality in various indications.