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In patients with syndrome X, cardiovascular magnetic resonance imaging demonstrates subendocardial hypoperfusion during the intravenous administration of adenosine, which is associated with intense chest pain. These data support the notion that the chest pain may have an ischemic cause.

In this Phase I clinical study, a novel ultrasmall superparamagnetic iron oxide contrast agent, NC100150 Injection (Nycomed Imaging, Oslo, Norway, a part of Nycomed Amersham), was used in two-dimensional magnetic resonance coronary angiography (MRCA). Safety and imaging data were acquired from 18 healthy male volunteers at both 0.5 and 1.5 T, before and after the administration of NC100150 Injection. Through-plane and in-plane images of the right coronary artery were analyzed. The postcontrast imaging sequences used prepulses and a high flip angle, to introduce T1 weighting. At 1.5 T (TE 2.6 msec), the throughplane coronary artery signal-to-noise ratio (SNR) (P ‫؍‬ 0.04), coronary artery-to-fat signal difference-to-noise ratio (SDNR) (P ‫؍‬ 0.001), coronary artery-to-myocardium SDNR (P F 0.001), and coronary artery delineation (P F 0.001) were improved by the administration of NC100150 Injection. For in-plane imaging, coronary artery delineation improved, but there were no significant changes in the SNR and SDNR. At 0.5 T, with the longer TE (6.7 msec) imaging sequence used, there was a reduction in the SNR (P ‫؍‬ 0.01), the fat SDNR (through-plane P ‫؍‬ 0.02; in-plane P ‫؍‬ 0.25), and the coronary artery diameter (P F 0.01 in both imaging planes). There was a trend toward improvement in the myocardial SDNR and coronary artery delineation. In conclusion, NC100150 Injection was given safely to 18 healthy subjects, with no major adverse reactions. Coronary artery delineation was improved in both imaging planes at 1.5 T, with a trend toward improvement at 0.5 T. At 1.5 T, with a short TE imaging sequence, the marked T1 shortening effects of NC100150 Injection were dominant, leading to an improvement in the quantitative parameters for the through-plane images. At 0.5 T, with a longer TE imaging sequence, the T2* effects of the contrast agent played a role in reducing the quantitative image parameters. With further optimization of imaging sequences, to take advantage of the long-lived intravascular T1 shortening effect of NC100150 Injection, further improvements in MRCA will be possible.

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In patients with NICM, CRT-D was superior to CRT-P in +MWF but not -MWF. These findings have implications for the choice of device therapy in patients with NICM.

AimsThere is a continuing debate as to whether cardiac resynchronization therapy-defibrillation (CRT-D) is superior to CRT-pacing (CRT-P), particularly in patients with non-ischaemic cardiomyopathy (NICM). We sought to quantify the clinical outcomes after primary prevention of CRT-D and CRT-P and identify whether these differed according to the aetiology of cardiomyopathy.Methods and resultsAnalyses were undertaken in the total study population of patients treated with CRT-D (n = 551) or CRT-P (n = 999) and in propensity-matched samples. Device choice was governed by the clinical guidelines in the United Kingdom. In univariable analyses of the total study population, for a maximum follow-up of 16 years (median 4.7 years, interquartile range 2.4–7.1), CRT-D was associated with a lower total mortality [hazard ratio (HR) 0.72] and the composite endpoints of total mortality or heart failure (HF) hospitalization (HR 0.72) and total mortality or hospitalization for major adverse cardiac events (MACE; HR 0.71) (all P < 0.001). After propensity matching (n = 796), CRT-D was associated with a lower total mortality (HR 0.72) and the composite endpoints (all P < 0.01). When further stratified according to aetiology, CRT-D was associated with a lower total mortality (HR 0.62), total mortality or HF hospitalization (HR 0.63), and total mortality or hospitalization for MACE (HR 0.59) (all P < 0.001) in patients with ischaemic cardiomyopathy (ICM). There were no differences in outcomes between CRT-D and CRT-P in patients with NICM.ConclusionIn this study of real-world clinical practice, CRT-D was superior to CRT-P with respect to total mortality and composite endpoints, independent of known confounders. The benefit of CRT-D was evident in ICM but not in NICM.

In this phase I clinical study, the new ultrasmall superparamagnetic iron oxide contrast agent, NC100150 Injection (Nycomed AS, Oslo, Norway, a part of Nycomed Amersham), was assessed for first-pass magnetic resonance myocardial perfusion studies and its ability to produce equilibrium signal changes, as a possible indicator of myocardial blood volume. Data were acquired in 18 healthy male volunteers at 0.5 T and 1.5 T. At both field strengths, first-pass studies using T1-weighted sequences were acquired. Long TE spinecho echoplanar imaging (EPI) was used at 0.5 T and short TE fast low-angle shot (FLASH) imaging at 1.5 T. With both sequences, T1 effects dominated the images for low doses, and time intensity curves potentially suitable for perfusion analysis were generated. At higher doses, T2 and T2* effects were observed. At 1.5 T, these predominantly affected the blood pool signal; however, at 0.5 T the myocardial signal was also involved, reflecting the relative T2 and T2* sensitivity of the spin-echo EPI sequence as a result of the long TE and long readout window, respectively. Equilibrium changes were assessed at both field strengths using T1-weighted FLASH sequences and in addition at 1.5 T using T2*-weighted gradient-echo EPI. With the T1weighted images at both field strengths, signal changes were observed in all subjects; however, no dose-response relationship could be shown. With the T2*-weighted EPI there was significantly lower signal (P F 0.05) with the 3 and 4 mg/kg doses than with the 2 mg/kg dose. In conclusion, NC100150 Injection is useful for first-pass myocardial perfusion using T1-weighted sequences; however, low doses in combination with short TE sequences are required to minimize sensitivity to T2* effects. Equilibrium signal changes can also be induced in the myocardium. More work is required to optimize the imaging sequences and dose of NC100150 Injection for first-pass studies and also to determine whether the equilibrium signal changes can be used to measure myocardial blood volume changes in ischemic heart disease.