Should we screen for coronary artery disease in asymptomatic chronic dialysis patients?

The hemodialysis population is characterized by a high prevalence of ‘asymptomatic’ coronary artery disease (CAD), which should be interpreted differently from asymptomatic disease in the general population. A hemodynamically significant stenosis may not become clinically apparent owing to impaired exercise tolerance and autonomic neuropathy. The continuous presence of silent ischemia may cause heart failure, arrhythmias, and sudden death. Whether revascularization of an asymptomatic dialysis patient improves outcome remains a moot point, although several observational studies and one small RCT suggest a benefit. It can therefore be defended to screen asymptomatic dialysis patients for CAD. A number of noninvasive screening tests are available, but none has proved equally practical and reliable in the dialysis population as in the general population. Myocardial perfusion scintigraphy (MPS) before and after a pharmacological stress such as dipyridamole can reveal both ischemia and myocardial scarring. When compared with coronary angiography, low sensitivities were reported and attributed to impaired vasodilation to dipyridamole in dialysis patients. A more likely explanation is that not every anatomical stenosis will lead to impaired coronary blood flow on MPS. Numerous studies have shown an incremental prognostic value of dipyridamole-MPS over clinical data for prediction of adverse cardiac events, in some studies even over coronary angiography. Pending the availability of high-quality evidence, in our opinion asymptomatic dialysis patients could undergo dipyridamole-MPS, followed by coronary angiography in case of an abnormal scan. This combined physiological and anatomical evaluation of the coronary circulation allows us to determine which coronary stenosis is clinically relevant and therefore should be revascularized

Camelid reporter gene imaging: a generic method for in vivo cell tracking

BACKGROUND: To combine the sensitivity of bioluminescent imaging (BLI) with the 3D and quantitative properties of pinhole single-photon emission computed tomography (SPECT)/micro-computed tomography (CT) (phSPECT/micro-CT), we generated stable cell lines that express a yellow-fluorescent protein (YFP) and Gaussia luciferase (GLuc) fusion protein (YFP/GLuc). For in vivo phSPECT detection of this YFP/GLuc protein, a nanobody, targeted against yellow and green fluorescent proteins (anti-YFP-Nb), was site specifically labelled with (99m)Tc. METHODS: Human embryonic kidney cells (HEK293T) were cultured and passaged every 3 days. 10E5 cells were transduced with YFP/GLuc-containing vector: both membrane-targeted (MT-YFP/GLuc) and non-targeted (YFP/GLuc) fusion proteins were developed. These vectors were compared against a SKOV-3 cell line stably expressing green fluorescent-firefly luciferase (GFP/Fluc) and HEK293T cells expressing red fluorescent protein in combination with a Gaussia luciferase (Red/GLuc). Transduction efficiencies were scored by fluorescence microscopy, and transduced cells were enriched by fluorescence-activated cell sorting (FACS). GLuc and FLuc functionality was tested in vitro by list-mode BLI. Subsequently, cells were transplanted subcutaneously in athymic (nu/nu) mice (MT-YFP/GLuc: n = 4, YFP/GLuc: n = 6, GFP/FLuc: n = 6, Red/GLuc: n = 4). Labelling efficiency of anti-YFP-Nb was measured using instant thin layer chromatography. One week after transplantation, (99m)Tc-labelled anti-YFP-Nb was injected intravenously and pinhole (ph) SPECT/micro-CT was performed, followed by in vivo BLI. RESULTS: Cells showed high levels of fluorescence after transduction. The cells containing the MT-YFP/GLuc were positive on fluorescence microscopy, with the fluorescent signal confined to the cell membrane. After cell sorting, transduced cells were assayed by BLI and showed a significantly higher light output both in vitro and in vivo compared with non-transduced HEK293T cells. The anti-YFP-Nb labelling efficiency was 98%, and subsequent phSPECT/micro-CT demonstrated visible cell binding and significantly higher transplant-to-muscle ratio for both the MT-YFP/GLuc and YFP/GLuc transplanted cells, compared with the GFP/FLuc and Red/GLuc group. CONCLUSION: This study provides a proof of principle for a nanobody-based cell tracking method, using a YFP/GLuc fusion protein and anti-YFP-Nb in a model of subcutaneously transplanted transduced HEK293T cells

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

BMIPP imaging to assess functional outcome in patients with acute and chronic left ventricular dysfunction

Assessment of myocardial viability is an important clinical issue for patient management during the acute and chronic stages of myocardial infarction. BMIPP (15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid) is a free fatty acid analogue which is trapped in the myocardium, thus permitting for metabolic imaging with single photon emission computerized tomography (SPECT). Less BMIPP than flow tracers that may be observed in the areas of infarction, may reflect the metabolic shift from fatty acid to glucose utilization in ischaemic myocardium. In this sense, the combined imaging of BMIPP and a flow tracer with SPECT may provide similar and important information as fluoro-18 deoxyglucose (FDG) and positron emission tomography (PET) regarding the assessment of myocardial viability. The purpose of this article is to review the clinical impact of BMIPP in patients with acute and with chronic left ventricular dysfunction for the identification of jeopardized but viable myocardium and the prediction of the functional outcome.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Performance characteristics of silicon photomultiplier based 15-cm AFOV TOF PET/CT

Abstract Background This paper describes the National Electrical Manufacturers Association (NEMA) system performance of the Discovery MI 3-ring PET/CT (GE Healthcare) installed in Bruges, Belgium. This time-of-flight (TOF) PET camera is based on silicon photomultipliers instead of photomultiplier tubes. Methods The NEMA NU2-2012 standard was used to evaluate spatial resolution, sensitivity, image quality (IQ) and count rate curves of the system. Timing and energy resolution were determined. Results Full width at half maximum (FWHM) of spatial resolution in radial, tangential and axial direction was 4.69, 4.08 and 4.68 mm at 1 cm; 5.58, 4.64 and 5.83 mm at 10 cm; and 7.53, 5.08 and 5.47 mm at 20 cm from the centre of the field of view (FOV) for the filtered backprojection reconstruction. For non-TOF ordered subset expectation maximization (OSEM) reconstruction without point spread function (PSF) correction, FWHM was 3.87, 3.69 and 4.15 mm at 1 cm; 4.80, 3.81 and 4.87 mm at 10 cm; and 7.38, 4.16 and 3.98 mm at 20 cm. Sensitivity was 7.258 cps/kBq at the centre of the FOV and 7.117 cps/kBq at 10-cm radial offset. Contrast recovery (CR) using the IQ phantom for the TOF OSEM reconstruction without PSF correction was 47.4, 59.3, 67.0 and 77.0% for the 10-, 13-, 17- and 22-mm radioactive spheres and 82.5 and 85.1% for the 28- and 37-mm non-radioactive spheres. Background variability (BV) was 16.4, 12.1, 9.1, 6.6, 5.1 and 3.8% for the 10-, 13-, 17-, 22-, 28- and 37-mm spheres. Lung error was 8.5%. Peak noise equivalent count rate (NECR) was 102.3 kcps at 23.0 kBq/ml with a scatter fraction of 41.2%. Maximum accuracy error was 3.88%. Coincidence timing resolution was 375.6 ps FWHM. Energy resolution was 9.3% FWHM. Q.Clear reconstruction significantly improved CR and reduced BV compared with OSEM. Conclusion System sensitivity and NECR are lower and IQ phantom’s BV is higher compared with larger axial FOV (AFOV) scanners like the 4-ring discovery MI, as expected from the smaller solid angle of the 3-ring system. The other NEMA performance parameters are all comparable with those of the larger AFOV scanners

Gated myocardial perfusion tomography versus gated blood pool tomography for the calculation of left ventricular volumes and ejection fraction

Left ventricular (LV) volume, and not only ejection fraction (EF), is a crucial parameter for assessing the severity of cardiac disease and determining the patient's prognosis. The purpose of this study was to compare LV volumes and EF computed automatically from gated blood pool tomography (gBPT), using QUBE, and from gated myocardial perfusion tomography (gMPT), using QGS, in the same patients with a known history of myocardial infarction. The effects of the extent and severity of the myocardial perfusion defects were investigated. Thirty-seven patients were injected in a random sequence with 740 MBq of technetium-99m human serum albumin and 925 MBq of Tc-99m-tetrofosmin, within an interval of 2 days. gBPT and gMPT were acquired on the same triple-head gamma camera using the following acquisition parameters: 360degrees step-and shoot rotation, 32 stops (96 projections), 30 s per stop, 64x64 matrix (pixel size 5.8 mm), 8 time bins (75% forward/backward framing). Projection data were reconstructed by filtered back-projection using a Butterworth filter. LV volumes calculated from gBPT correlated well with LV volumes measured on gMPT (r=0.93 for end-diastolic volume and 0.95 for end-systolic volume). Volumes above 200 ml, however, were substantially higher with gMPT than with gBPT. These discrepancies were related to the severity, but not the extent, of the perfusion defects. There was also good agreement between gBPT and gMPT for the LVEF (r=0.91). On the Bland-Altman plot, no trend but a systematic error of 5.57% and a random error of 6.85% could be found. For the LVEF, the differences between the gated tomographic techniques were related neither to the extent nor to the severity of the perfusion defects. In conclusion, LV volumes and EF computed on gMPT correlated well with those measured on gBPT. Discrepancies were observed for large volumes presumably because of inaccuracies of gMPT in patients with severe perfusion defects