Tilman Hickethier

Baroreflex activation therapy in patients with pre-existing implantable cardioverter-defibrillator: compatible, complementary therapies

AIMS The Neo™ System (CVRx) is an implantable device, CE certified for the treatment of resistant hypertension and investigationally used to treat systolic heart failure by electrical stimulation of the carotid baroreceptors. It is unknown whether interaction might exist between the Neo System and implantable cardioverter-defibrillators (ICDs). METHODS AND RESULTS Compatibility of the Neo device was tested in seven consecutive patients with pre-existing ICDs. Intra- and post-operative testing was completed with ICD and Neo settings programmed to provoke interaction. Intracardiac electrograms were printed to determine interaction with the ICD. Interaction testing during implantation and follow-up showed that there was no device-device interaction. No interaction was observed at maximum atrial and ventricular sensitivity settings and maximum Neo output settings. CONCLUSION Combined therapy with the Neo device and at least in this study reported that transvenous ICD systems can be performed safely.

Acute on/off effects and chronic blood pressure reduction after long-term baroreflex activation therapy in resistant hypertension.

Background: Baroreflex activation therapy (BAT) by electrical stimulation of baroreceptors at the carotid sinus is a promising therapeutic approach to reduce elevated blood pressure (BP). To assess the efficacy of long-term BAT, we investigated acute BP alterations after device deactivation and reactivation (on/off effects) in patients on chronic BAT, as well as chronic BP reductions. Method: Resistant hypertension patients (n = 17) were enrolled in an open-label, single-arm evaluation of unilateral BAT after exclusion of secondary hypertension. Initial eligibility criteria were SBP≥  140 mmHg, despite stable medical therapy with at least three antihypertensive drugs including at least one diuretic. For on/off testing, several office cuff BP measurements were performed: at rest with activated device, 4–6 min after deactivation, and 4–6 min after reactivation. Results: Before BAT, mean office cuff BP was 179 ± 25 over 98 ± 18 mmHg. At the time of on/off testing (15.1 ± 8.7 months after initial activation and before deactivation), BP was reduced to 147 ± 29 over 84 ± 20 mmHg. On deactivation, SBP increased to 158 ± 38 mmHg (P = 0.004) and DBP to 89 ± 23 mmHg (P = 0.04). After reactivation, SBP decreased to 144 ± 34 mmHg (P = 0.002 vs. deactivation) and DBP to 83 ± 23 mmHg (P = 0.009). There was no correlation between duration of chronic BAT and systolic or diastolic acute on/off response. Conclusion: Unilateral BAT reduces BP in patients with resistant hypertension in the long term. There is a significant on/off effect on BP, supporting the efficacy of BAT. The acute on/off response to BAT does not depend on treatment duration. Thus, no evidence of tolerance over time to chronic BAT was found.

Histomorphometric evaluation of ischemia-reperfusion injury and the effect of preservation solutions histidine-tryptophan-ketoglutarate and University of Wisconsin in limb transplantation.

Background The effect of cold ischemia (CI) in vascularized composite allotransplantation is unknown. We herein assess tissue-specific damage, acceptable CI time, and the effect of preservation solutions in a syngenic rat hindlimb transplant model. Methods Lewis rat limbs were flushed and stored for 2, 10, or 30 hr CI in saline, histidine-tryptophan-ketoglutarate or University of Wisconsin preservation solution before transplantation. Morphologic alterations, inflammation, and damage of the individual tissues were analyzed on day 10 using histomorphology, confocal, light, and transmission-electron microscopy. Results Two-hour CI led to mild inflammation of tissues on day 10, whereas 10-hr and 30-hr CI resulted in massive inflammation and tissue damage. Although muscle was mainly affected after prolonged CI (≥10 hr), nerve was affected in all CI groups. A perineural cell infiltrate, hypercellular appearance, pronounced vacuolization, and mucoid degeneration, appearing as Wallerian degeneration, were observed. Staining with propidium iodide and Syto 16 revealed a decrease in viable muscle cell nuclei in the anterior tibial muscle on day 10 in all groups, which was most pronounced in 10-hr and 30-hr CI animals. Transmission-electron microscopy indicated that a large number of mitochondria were degenerated in the 10-hr and 30-hr CI groups. Histidine-tryptophan-ketoglutarate preservation solution slightly decreased inflammation and tissue damage compared to University of Wisconsin-treated and saline-treated animals, especially in skin and muscle when CI times did not exceed 10 hr. Conclusion Severe inflammation and tissue damage are observed after prolonged CI in muscle and nerve. Ischemia times in vascularized composite allotransplantation should be kept as short as possible and certainly below 10 hr.

Image quality evaluation of dual-layer spectral detector CT of the chest and comparison with conventional CT imaging

OBJECTIVES To evaluate image quality parameters of virtual mono-energetic (MonoE) and conventional (CR) imaging derived from a dual-layer spectral detector CT (DLCT) in oncological follow-up venous phase imaging of the chest and comparison with conventional multi-detector CT (CRMDCT) imaging. MATERIALS AND METHODS A total of 55 patients who had oncologic staging with conventional CT and DLCT of the chest in venous phase were included in this study. Established image quality parameters were derived from all datasets in defined thoracic landmarks. Attenuation, image noise, and signal-/contrast- to noise ratios (SNR, CNR) were compared between CRDLCT and MonoE as well as CRMDCT imaging. Two readers performed subjective image analysis. RESULTS CRMDCT showed significant lower attenuation values compared to CRDLCT and MonoE at 40-70keV (p≤0.05). Moreover, MonoE at 40-70keV revealed significantly higher attenuations values compared to CRDLCT (p<0.001). Noise was statistically lower in CRMDCT compared with CRDLCT and MonoE at 40keV (11.4±2.3 HU vs. 12.0±3.1 HU vs. 11.7±5.2 HU; p<0.001). In contrast, all MonoE levels showed significantly lower noise levels compared to CRDLCT (p<0.001). SNR was not significantly different between CRMDCT and CRDLCT (13.5±3.7 vs. 14.4±5.3; p>0.99). SNR values were significantly increased for MonoE at 40-80keV compared to CRMDCT and CRDLCT (p<0.001). CRDLCT and MonoE (40-70keV) from DLCT revealed significantly higher CNR values than CRMDCT (p<0.001). In subjective analysis, MonoE at 40keV surpassed all other image reconstructions except for noise in MonoE at 70 keV. CONCLUSION In dual-layer spectral detector CT, MonoE at low keV showed superior image quality compared to conventional images derived from the same system and may therefore be added to clinical routine imaging protocols. Whether MonoE reconstructions yield additional diagnostic information is still unknown.

Non-invasive imaging of bioresorbable coronary scaffolds using CT and MRI: First in vitro experience

BACKGROUND Accurate assessment of coronary stents after PCI using non-invasive imaging remains challenging despite technological improvements. New bioresorbable vascular scaffolds (BVS) have recently become available promising improved non-invasive imaging properties, which however have not be examined specifically yet. Therefore we investigated CT and MRI visualization properties of the only two CE-marked coronary BVSs. METHODS The Abbott Absorb and the Elixir DESolve BVS were placed in plastic tubes filled with contrast agent and scanned with a latest generation CT respectively MR system. For CT image quality was assessed by two blinded, independent readers and in-scaffold diameter difference as well as in-scaffold attenuation difference were measured. For MRI in-scaffold signal intensity, in-scaffold lumen visibility and in-scaffold signal homogeneity were measured. RESULTS In CTA both BVSs showed no significant difference to nominal tube diameter (DESolve 101%, Absorb 100%) and to nominal tube attenuation (DESolve 96%, Absorb 98%) and were both rated with the highest score for unrestricted lumen visualization. In MRA both BVSs showed unimpaired signal intensity (DESolve 103%, Absorb 100%), lumen visibility (DESolve 92%, Absorb 89%) and lumen homogeneity (DESolve SD 7.1%, Absorb SD 9.5%) when compared to the unstented tube. There was no significant difference between CTA and MRA results of both BVSs. CONCLUSIONS Coronary BVSs show no relevant impairment for subjective and objective measures of in-stent lumen visualization by CT and MRI and will therefore allow reliable non-invasive assessment of coronary artery patency after PCI with deployment of a BVS, which is an (additional) advantage when compared to conventional stents.

Targeting the Kv1.3 potassium channel for immunosuppression in vascularized composite allotransplantation – a pilot study

Kv1.3‐channels are critically involved in activation and function of effector memory T cells. Blocking Kv1.3‐channels was investigated for its effect on skin rejection in a rat limb‐transplantation‐model. Animals received the Kv1.3‐blocker correolide C systemically or locally as intra‐graft‐treatment in combination with tacrolimus. Systemic (intraperitoneal) administration of correolide C resulted in slight, but significant prolongation of allograft survival compared with untreated and placebo treated controls. In 4/6 correolide C treated animals, histology showed an intact epidermis and a mild infiltrate by day 10. High correolide C plasma trough levels correlated with prolonged allograft survival. A decrease in CD4+ and CD8+ effector memory T cells was observed in allograft skin, peripheral blood and the spleen on day 5. When applied subcutaneously in combination with systemic tacrolimus (30 days+/−anti‐lymphocyte serum) detectable, but insignificant prolongation of graft survival was achieved. 2/5 animals showed an intact epidermis and a mild infiltrate until day 45. Tapering systemic tacrolimus and weaning on day 50 resulted in rejection by day 55, regardless of local correolide C treatment. Subcutaneous injection did not lead to systemic plasma levels. The Kv1.3‐channel is a potential drug target worth exploring in more detail for immunosuppression in vascularized composite allotransplantation.

Baroreflex activation therapy: a new treatment option for heart failure with reduced ejection fraction.

Sympathovagal imbalance plays a major role in the progression of heart failure with reduced ejection fraction. Baroreflex activation therapy (BAT) by electrical stimulation of baroreceptors located at the carotid sinus can reduce sympathetic and increase parasympathetic tone. This review provides an overview on the concept of BAT in heart failure with reduced ejection fraction and available preclinical and clinical data. Animal studies of BAT in heart failure with reduced ejection fraction have demonstrated a decline in plasma norepinephrine, an improved left ventricular ejection fraction, a reduced susceptibility to induced ventricular arrhythmias and a survival benefit. First clinical data from uncontrolled studies suggest a relevant improvement in muscle sympathetic nerve activity, ejection fraction, 6-min walk distance, New York Heart Association (NYHA) class and hospitalization rate. BAT appears to be safe in this severely ill patient population.

Utilization of virtual mono-energetic images (MonoE) derived from a dual-layer spectral detector CT (SDCT) for the assessment of abdominal arteries in venous contrast phase scans

OBJECTIVES To investigate the utilization of virtual mono-energetic images (MonoE) at low kiloelectron volt (keV) levels derived from a dual-layer spectral detector CT (SDCT) for the assessment of abdominal arteries in venous contrast phase scans using arterial phase imaging as an internal reference standard. MATERIALS AND METHODS A total of 50 patients who received arterial and venous phase imaging of the abdomen on a SDCT system were included in this study. Absolute attenuation, noise, signal- and contrast to noise ratios (SNR; CNR) as well as arterial diameters in defined landmarks were assessed. In arterial phase, conventional reconstructions (CRART) as well as MonoEART at 40keV and in venous phase, conventional reconstructions (CRVEN) as well as MonoEVEN at 70 and 40keV were investigated and intra-individual comparisons were performed. If an artery stenosis (10 patients) was present, the degree of stenosis was assessed according to the system of the North American Symptomatic Carotid Endarterectomy Trial (NASCET). RESULTS MonoE 40keV yielded significantly higher attenuation values (in arterial as well as in venous phase) compared to CRART (p<0.001) while noise levels were substantially low. This resulted in markedly superior SNR and CNR in large vessel compared to CRART. Luminal diameters were significantly smaller in MonoE 40keV in both contrast phases compared to CRART (p<0.001), whereas no significant differences were found between both MonoE reconstructions (p≥0.92). The degree of vessel stenosis was significantly higher in MonoE 40keV of both contrast phases compared to CRART (p≥0.02). CONCLUSION MonoE at low keV of venous contrast phase scans derived from a novel SDCT are suitable for the assessment of arteries in the abdomen and subsequent stenosis assessment. However, MonoE at 40keV constantly showed significant smaller luminal diameters than the corresponding conventional reconstructions (including the reference standard). This is possibly due to an improved differentiation of the vessel lumen from the wall and raises the question, which imaging technique should be used as an appropriate reference standard for vascular SDCT imaging studies.

Cerebral white matter lesion burden is associated with the degree of aortic valve calcification and predicts peri‐procedural cerebrovascular events in patients undergoing transcatheter aortic valve implantation (TAVI)

To investigate the impact of aortic valve calcification and brain morphology on acute peri‐procedural cerebrovascular events (CVEs) in patients undergoing transcatheter aortic valve implantation (TAVI).

Photon-counting CT: high-resolution imaging of coronary stents

Purpose The aim of this study was to investigate computed tomography (CT) imaging characteristics of coronary stents using a novel photon-counting detector (PCD) in comparison with a conventional energy-integrating detector (EID). Materials and Methods In this in vitro study, 18 different coronary stents were expanded in plastic tubes of 3 mm diameter, were filled with contrast agent (diluted to an attenuation of 250 Hounsfield units [HU] at 120 kVp), and were sealed. Stents were placed in an oil-filled custom phantom calibrated to an attenuation of −100 HU at 120 kVp for resembling pericardial fat. The phantom was positioned in the gantry at 2 different angles at 0 degree and 90 degrees relative to the z axis, and was imaged in a research dual-source PCD-CT scanner. Detector subsystem “A” used a standard 64-row EID, while detector subsystem “B” used a PCD, allowing high-resolution scanning (detector pixel-size 0.250 × 0.250 mm in the isocenter). Images were obtained from both detector systems at identical tube voltage (100 kVp) and tube current-time product (100 mA), and were both reconstructed using a typical convolution kernel for stent imaging (B46f) and using the same reconstruction parameters. Two independent, blinded readers evaluated in-stent visibility and measured noise, intraluminal stent diameter, and in-stent attenuation for each detector subsystem. Differences in noise, intraluminal stent diameter, and in-stent attenuation where tested using a paired t test; differences in subjective in-stent visibility were evaluated using a Wilcoxon signed-rank test. Results Best results for in-stent visibility, noise, intraluminal stent diameter, and in-stent attenuation in EID and PCD were observed at 0-degree phantom position along the z axis, suggesting higher in-plane compared with through-plane resolution. Subjective in-stent visibility was superior in coronary stent images obtained from PCD compared with EID (P < 0.001). Mean in-stent diameter was 28.8% and 8.4% greater in PCD (0.85 ± 0.24 mm; 0.83 ± 0.14 mm) as compared with EID acquisitions (0.66 ± 0.21 mm; 0.76 ± 0.13 mm) for both 0-degree and 90-degree phantom positions, respectively. Average noise was significantly lower (P < 0.001) for PCD (5 ± 0.2 HU) compared with EID (8.3 ± 0.2 HU). The increase in in-stent attenuation (0 degree: &Dgr; 245 ± 163 HU vs &Dgr; 156.5 ± 126 HU; P = 0.006; 90 degrees: &Dgr; 194 ± 141 HU vs &Dgr; 126 ± 78 HU; P = 0.001) was significantly lower for PCD compared with EID acquisitions. Conclusions At matched CT scan protocol settings and identical image reconstruction parameters, the PCD yields superior in-stent lumen delineation of coronary artery stents as compared with conventional EID arrays.