Peter Fries

Effect of renal denervation on left ventricular mass and function in patients with resistant hypertension: data from a multi-centre cardiovascular magnetic resonance imaging trial

AIMS 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. METHODS AND RESULTS 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). CONCLUSIONS Catheter-based RDN significantly reduced BP and LVMI and improved EF and circumferential strain in patients with resistant hypertension, occurring partly BP independently.

Heart rate reduction by If-inhibition improves vascular stiffness and left ventricular systolic and diastolic function in a mouse model of heart failure with preserved ejection fraction

AIMS In diabetes mellitus, heart failure with preserved ejection fraction (HFPEF) is a significant comorbidity. No therapy is available that improves cardiovascular outcomes. The aim of this study was to characterize myocardial function and ventricular-arterial coupling in a mouse model of diabetes and to analyse the effect of selective heart rate (HR) reduction by If-inhibition in this HFPEF-model. METHODS AND RESULTS Control mice, diabetic mice (db/db), and db/db mice treated for 4 weeks with the If-inhibitor ivabradine (db/db-Iva) were compared. Aortic distensibility was measured by magnetic resonance imaging. Left ventricular (LV) pressure-volume analysis was performed in isolated working hearts, with biochemical and histological characterization of the cardiac and aortic phenotype. In db/db aortic stiffness and fibrosis were significantly enhanced compared with controls and were prevented by HR reduction in db/db-Iva. Left ventricular end-systolic elastance (Ees) was increased in db/db compared with controls (6.0 ± 1.3 vs. 3.4 ± 1.2 mmHg/µL, P < 0.01), whereas other contractility markers were reduced. Heart rate reduction in db/db-Iva lowered Ees (4.0 ± 1.1 mmHg/µL, P < 0.01), and improved the other contractility parameters. In db/db active relaxation was prolonged and end-diastolic capacitance was lower compared with controls (28 ± 3 vs. 48 ± 8 μL, P < 0.01). These parameters were ameliorated by HR reduction. Neither myocardial fibrosis nor hypertrophy were detected in db/db, whereas titin N2B expression was increased and phosphorylation of phospholamban was reduced both being prevented by HR reduction in db/db-Iva. CONCLUSION In db/db, a model of HFPEF, selective HR reduction by If-inhibition improved vascular stiffness, LV contractility, and diastolic function. Therefore, If-inhibition might be a therapeutic concept for HFPEF, if confirmed in humans.

Valve-preserving root replacement in bicuspid aortic valves

OBJECTIVE Bicuspid aortic valve anatomy is associated with aortic root aneurysm in a relevant proportion of patients. These patients require root replacement for prognostic reasons, and the valve may be preserved. The objective of this analysis is to analyze the early and late outcomes of root remodeling for bicuspid aortic valve. METHODS Between November 1995 and December 2009, 153 patients (133 male) were treated by root remodeling in the presence of a bicuspid aortic valve. Acute dissection was present in 6 individuals. In 137 instances, additional correction of cusp pathology was achieved by plication (n = 119), triangular resection (n = 59), and implantation of a pericardial patch (n = 27). Follow-up ranges from 3 months to 14.5 years (mean, 4.9 ± 3.8 years; cumulative, 757 years) and is complete in 99.3%. RESULTS One patient died of intracranial hemorrhage in the hospital (mortality 0.7%). Survival at 5 and 10 years was 99% and 91%, respectively. Seven patients required reoperation for stenosis (n = 1) or recurrent aortic insufficiency (n = 6) between 1 month and 11 years postoperatively. The aortic valve was re-repaired in 2 cases. Freedom from reoperation at 5 and 10 years was 95%; freedom from valve replacement was 97%. Freedom from valve-related complications was 91% at 5 and 10 years. CONCLUSIONS Root remodeling for aortic root aneurysm in the presence of a bicuspid aortic valve can be performed with a low morbidity and mortality. The long-term stability of the reconstructed aortic valve is excellent if normal valve configuration is achieved. The occurrence of late stenosis seems to be rare, and freedom from valve-related complications is high.

Magnetic resonance imaging of the spine at 3 Tesla.

Magnetic resonance imaging (MRI) has developed dramatically in the 25 years since its clinical introduction. Advances in hardware design have included the development of high field magnets and more sophisticated and sensitive coils. Improvements in sequences, data sampling, and postprocessing software have benefited the attainable spatial and temporal resolution to the point at which the fine depiction of anatomical structure and pathological processes is now routine. As in other radiological areas, the most recent advances in MRI have proven highly valuable in the field of musculoskeletal radiology where the lack of radiation, high soft tissue contrast, and capacity for multiplanar or three-dimensional imaging have made MRI the imaging modality of choice. Particular benefits are seen in diagnostic imaging of the spine where MRI is clearly superior to both conventional radiography and computed tomography. In this article, we discuss the impact of the most recent technological advance in MRI, namely the advent of 3 Tesla (3-T) imaging, on diagnostic imaging of the spine. Comparisons are drawn with imaging at 1.5 T, and emphasis is placed on MR physics and on the benefits and principal difficulties associated with spine imaging at high field strength.

Brain tumor enhancement in magnetic resonance imaging at 3 tesla: intraindividual comparison of two high relaxivity macromolecular contrast media with a standard extracellular gd-chelate in a rat brain tumor model.

Objectives:The aim of this study was to evaluate lesion enhancement (LE) and contrast-to-noise ratio (CNR) properties of P846, a new intermediate sized, high relaxivity Gd-based contrast agent at 3 Tesla in a rat brain glioma model, and to compare this contrast agent with a high relaxivity, macromolecular compound (P792), and a standard extracellular Gd-chelate (Gd-DOTA). Materials and Methods:Seven rats with experimental induced brain glioma were evaluated using 3 different contrast agents, with each MR examination separated by at least 24 hours. The time between injections assured sufficient clearance of the agent from the tumor, before the next examination. P792 (Gadomelitol, Guerbet, France) and P846 (a new compound from Guerbet Research) are macromolecular and high relaxivity contrast agents with no protein binding, and were compared with the extracellular agent Gd-DOTA (Dotarem, Guerbet, France). T1w gradient echo sequences (TR/TE 200 milliseconds/7.38 milliseconds, flip angle = 90°, acquisition time: 1:42 minutes:sec, voxel size: 0.2 × 0.2 × 2.0 mm3, FOV = 40 mm, acquisition matrix: 256 × 256) were acquired before and at 5 consecutive time points after each intravenous contrast injection in the identical slice orientation, using a dedicated 4-channel head array animal coil. The order of contrast media injection was randomized, with however Gd-DOTA used either as the first or second contrast agent. Contrast agent dose was adjusted to compensate for the different T1 relaxivities of the 3 agents. Signal-to-noise ratio, CNR, and LE were evaluated using region-of-interest analysis. A veterinary histopathologist confirmed the presence of a glioma in each subject, after completion of the imaging study. Results:P792 showed significantly less LE as compared with Gd-DOTA within the first 7 minutes after contrast agent injection (P < 0.05) with, however, reaching comparable LE values at 9 minutes after injection (P = 0.07). However, P792 provided significantly less CNR as compared with Gd-DOTA (P < 0.05) for all examination time points. P846 provided comparable but persistent LE as compared with Gd-DOTA (P < 0.05) and demonstrated significantly greater LE and CNR when compared with P792 (P < 0.05). No statistically significant differences between CNR values for Gd-DOTA and P846 were noted for all examination time points (P < 0.05), with P846 administered at one-fourth the dose as compared with Gd-DOTA. Conclusion:The intravascular contrast medium P792 showed significantly less LE and CNR in comparison to Gd-DOTA and P846, suggesting that it does not show marked extravasation from tumor neocapillaries and does not significantly cross the disrupted blood brain-barrier in this rat glioma model. In distinction, P846 provides comparable enhancement properties at a field strength of 3 Tesla to the extracellular contrast agent Gd-DOTA, using the adjusted dose, suggesting that it crosses the disrupted blood-brain-barrier and tumor capillaries, most likely based on the decreased molecular weight as compared with P792. At the same time, the high relaxivity of this compound allows for decreasing the injected gadolinium dose by a factor of 4 whereas providing comparable enhancement properties when compared with a standard extracellular Gd-chelate (Gd-DOTA) at a dose of 0.1 mmol/kg body weight.

Diffusion-weighted imaging in patients with acute brain ischemia at 3 T: current possibilities and future perspectives comparing conventional echoplanar diffusion-weighted imaging and fast spin echo diffusion-weighted imaging sequences using BLADE (PROPELLER).

Objectives:To compare diffusion-weighted imaging (DWI) based on a fast spin echo (FSE) sequence using BLADE (PROPELLER) with conventional DWI-echoplanar imaging (EPI) techniques at 3 T and to demonstrate the influence of hardware developments on signal-to-noise ratio (SNR) with these techniques using 12- and 32-channel head coils. Materials and Methods:Fourteen patients with brain ischemia were evaluated with DWI using EPI and FSE BLADE sequences, with a 12-channel head coil, in the axial plane and 1 additional plane (either sagittal or coronal). SNR and CNR were calculated from region-of-interest measurements. Scans were evaluated in a blinded fashion by 2 experienced neuroradiologists. SNR of both DWI techniques was evaluated in 12 healthy volunteers using different parallel imaging (PI) factors (for the EPI sequence) and both the 12- and 32-channel coils. Results:DWI-BLADE sequences acquired with the 12-channel coil revealed a significant reduction in SNR (mean ± SD) of ischemic lesions (SNRlesion [5.0 ± 2.5]), normal brain (SNRbrain [3.0 ± 1.9]), and subsequently in CNR (3.0 ± 1.8) as compared with the DWI-EPI sequence (SNRlesion [9.3 ± 5.2], SNRbrain [7.7 ± 3.5], CNR [6.1 ± 2.8], P < 0.001). Despite this reduction in SNR and CNR, the blinded read revealed a marked preference for the DWI-BLADE sequence, or equality between the sequences, in the majority of patients because lesion detection was degraded by susceptibility artifacts on axial DWI-EPI scans in 14% to 43% of cases (but in no instance with the DWI-BLADE sequence). In particular, preference for the DWI-BLADE sequence or equality between the 2 techniques for lesion detection in the brainstem and cerebellum was observed. On some DWI-BLADE scans, in the additional plane, radial-like artifacts degraded lesion detection.In volunteers, SNR was significantly improved using the 32-channel coil, irrespective of scan technique. Comparing DWI-EPI acquired with the 12-channel coil (iPAT = 2) to DWI-BLADE acquired with the 32-channel coil, comparable SNR values were obtained. The 32-channel coil also makes feasible, with DWI-EPI, an increase in the PI factor to 4, which allows for a further reduction of bulk susceptibility artifacts. However, still DWI-BLADE sequences performed better because of absence of bulk susceptibility artifacts at comparable SNR values. Conclusion:Despite lower SNR at comparable PI factors, DWI-BLADE sequences acquired using the 12-channel coil are preferable in most instances, as compared with DWI-EPI sequences, because of the absence of susceptibility artifacts and subsequently improved depiction of ischemic lesions in the brainstem and cerebellum. With the 32-channel coil, recently FDA approved, DWI-BLADE acquired with an iPAT = 2 provides comparable SNR without bulk susceptibility artifacts as compared with the DWI-EPI sequences acquired for clinical routine to date and has the potential to replace the standard DWI technique for special indications like DWI of the cerebellum and the brainstem or in presence of metallic implants or hemorrhage.

Paclitaxel-coated balloon angioplasty for symptomatic central vein restenosis in patients with hemodialysis fistulas.

Purpose: To report a retrospective observational analysis of standard balloon angioplasty (BA) vs. paclitaxel-coated balloon angioplasty (PCBA) for symptomatic central vein restenoses in patients with impaired native hemodialysis fistulas. Methods: A retrospective review was conducted of 27 consecutive patients (15 men; mean age 66±13.8 years, range 39–90) with 32 central vein stenoses (CVS; 6 axillary, 11 subclavian, 12 brachiocephalic, and/or 3 superior caval veins) treated successfully using BA. Freedom from reintervention after BA of de novo lesions was 7.4±7.9 months (range 1–24). Twenty-five (92.6%) patients developed symptomatic restenoses and were treated one or more times by BA (n=32) or PCBA (n=20) using custom-made paclitaxel-coated balloons (diameter 6–14 mm). Results: Technical (<30% residual stenosis) and clinical (functional fistula) success rates for the initial and secondary angioplasty procedures were 100%. No minor/major procedure-associated complications occurred. Mean follow-up was 18.4±17.5 months. Kaplan-Meier analysis for freedom from target lesion revascularization (TLR) found PCBA superior to BA (p=0.029). Median freedom from TLR after BA was 5 months; after PCBA, >50% of patients were event-free during the observation period (mean freedom from TLR 10 months). Restenosis intervals were prolonged by PCBA (median 9 months) vs. BA (median 4 months; p=0.023). Conclusion: Paclitaxel-coated balloon angioplasty of central vein restenosis in patients with hemodialysis shunts yields a statistically significant longer freedom from TLR compared to standard balloon angioplasty.

Adenosine A1 receptor activation attenuates cardiac hypertrophy and fibrosis in response to α1‐adrenoceptor stimulation in vivo

Adenosine has been proposed to exert anti‐hypertrophic effects. However, the precise regulation and the role of the different adenosine receptor subtypes in the heart and their effects on hypertrophic signalling are largely unknown. We aimed to characterize expression and function of adenosine A1 receptors following hypertrophic stimulation in vitro and in vivo.

Comparison of retrospectively self-gated and prospectively triggered FLASH sequences for cine imaging of the aorta in mice at 9.4 Tesla.

Objective:A critical problem in cardiovascular MRI in small rodents is adjusting the sequence acquisition to the high heart and respiratory rates. The aim of this study was to compare a retrospectively self-gated fast low angle shot navigator (RSG-FLASH) sequence with a conventional prospectively triggered (PT-FLASH) sequence for cine imaging of the ascending aorta in mice at 9.4 T. Material and Methods:Ten C57/BL6 mice were examined with a horizontal bore 9.4 Tesla MRI animal scanner using a dedicated 2 × 2 phased-array surface coil. We acquired a RSG-FLASH sequence (RSG-FLASH sequences (repetition time (TR) / echo time (TE) = 6.5/2.5 ms, flip angle (FA) = 10 degrees, field of view (FOV) = 2 × 2 cm, matrix = 384 × 384, slice thickness = 1 mm, 25 movie frames) perpendicular to the ascending aorta using the IntraGate technique. At the same position, we performed a PT-FLASH sequence (TR/TE = 6.5/2.1 ms, FA = 10 degrees, FOV = 2 × 2 cm, matrix = 384 × 384, slice thickness = 1 mm) in which the maximum number of movie frames had to be adjusted to the interval between two R-peaks (RR interval) of the electrocardiogram (ECG) with: number of frames = RR interval / TR.” Cross-sectional vessel areas at end-systole (AES) and end-diastole (AED) were measured to determine the aortic strain (&Dgr;A = (AES−AED)/AED). Two blinded readers rated the sequences for presence of flow and trigger artifacts and their influence on the depiction of the blood/vessel-wall interface. Irregularities in displaying the cardiac cycle and the overall suitability of the sequence for aortic strain evaluation were assessed using a 5-level ordinal scale. Statistical differences were analyzed using Student t test and Wilcoxon signed rank test (P < 0.05). Intra- and interobserver variability was evaluated using Bland-Altman analyses. Results:No significant differences were noted between techniques regarding the measured vessel areas (AED: P = 0.07, AES: P = 0.34), &Dgr;A: P = 0.1). Similarly, there were no significant differences in heart (P = 0.06) and respiratory (P = 0.24) rates. The acquisition time for RSG-FLASH sequence was significantly shorter (P = 0.04). Significantly fewer flow and trigger artifacts were noted by both readers with the RSG-FLASH sequence. Likewise, both readers considered the RSG-FLASH sequence to be superior for depiction of the blood/vessel-wall interface. The RSG-FLASH sequence was also rated superior regarding irregularities in displaying the cardiac cycle and in terms of overall suitability for evaluation of AED, AES, and aortic strain (P < 0.05 each). Conclusion:RSG-FLASH is preferable for cine imaging of the aorta. It provides the same quantitative data as PT-FLASH cine imaging but is less prone to flow and trigger artifacts. RSG-FLASH permits more homogeneous depiction of the cardiac cycle and is faster than the PT-FLASH sequence. PT-FLASH is more prone to misregistration of the respiratory cycle or the ECG by the external monitoring device used for acquisition. This effect may be even more pronounced in animals with disease models that are less stable in terms of heart and respiration rate during anesthesia.

A1 receptor activation attenuates cardiac hypertrophy and fibrosis in response to α1‐adrenergic stimulation in vivo

Adenosine has been proposed to exert anti‐hypertrophic effects. However, the precise regulation and the role of the different adenosine receptor subtypes in the heart and their effects on hypertrophic signalling are largely unknown. We aimed to characterize expression and function of adenosine A1 receptors following hypertrophic stimulation in vitro and in vivo.