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Myocardial perfusion in type 2 diabetes with left ventricular hypertrophy: normalisation by acute angiotensin-converting enzyme inhibition

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

The purpose of this study was to assess whether acute angiotensin-converting enzyme (ACE) inhibition would improve myocardial perfusion and perfusion reserve in a subpopulation of normotensive patients with diabetes and left ventricular hypertrophy (LVH), both independent risk factors of coronary disease. Using positron emission tomography (PET), we investigated the response of regional myocardial perfusion to acute ACE inhibition with i.v. infusion of perindoprilat (vs saline infusion as control, minimum interval 3 days) in 12 diabetic patients with LVH. Myocardial perfusion was quantified with PET using nitrogen-13 ammonia infused at rest and during dipyridamole hyperaemia. Twelve healthy control subjects were included in the study, five of whom were also studied with perindoprilat. Mean blood pressure in normo-albuminuric, asymptomatic patients was 123±7/65±9 mmHg. Compared with controls, maximal perfusion was reduced in patients (1.8±0.6 vs 2.5±1.0 ml min−1 g−1; P<0.05), and perfusion reserve was also lower, at borderline significance (2.7±1.0 vs 3.6±1.3; P=0.059). During perindoprilat infusion, myocardial perfusion reserve in patients increased to 3.9±0.9 (P<0.001) due to normalisation of maximal perfusion (2.3±0.5 ml min−1 g−1, P<0.01). In the five control subjects both resting and hyperaemic perfusion remained unchanged during perindoprilat infusion. It is concluded that acute ACE inhibition with perindoprilat improves maximal achieved myocardial perfusion in non-hypertensive patients with diabetes and LVH.

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Acknowledgements

We would like to thank Sam Gambhir for the supply of the SIMPLE software package, Helle Jung Larsen for her technical assistance and Ulrik Hesse for his help with the statistical calculations.

The study was supported by grants from the Danish Heart Foundation, Servier International, and the John and Birthe Meyer Foundation.

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Authors and Affiliations

  1. Department of Clinical Physiology and Nuclear Medicine, KF 4011, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100, Copenhagen, Denmark

    Birger Hesse, Christian Meyer, Jens D. Hove, Soeren Holm & Klaus F. Kofoed

  2. Steno Diabetes Center, Gentofte, Denmark

    Flemming S. Nielsen, Asako Sato & Hans-Henrik Parving

  3. Department of Medicine, Cape Heart Center, University of Cape Town, South Africa

    Lionel H. Opie

  4. Department of Internal Medicine, Naestved County Hospital, Denmark

    Lia E. Bang & Tage L. Svendsen

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  1. Birger Hesse
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Correspondence to Birger Hesse.

Appendix

Appendix

PET scanning acquisition

The study was performed with a whole-body tomograph (Advance, General Electric Medical Systems, Milwaukee, WI), with 18 crystal rings forming 35 two-dimensional imaging planes spaced by 4.25 mm, and an intrinsic spatial resolution of 4–6 mm full-width at half-maximum (FWHM). The gantry width had a diameter of 55 cm, and the axial field of view was 15.2 cm. Two pin sources with germanium-68 were used for the blank and transmission scan acquisitions. Corrections for dead time, random sequence, attenuation, scatter and decay were applied and the images were reconstructed to an effective in-plane resolution of 7 mm FWHM, using a Hanning filter. Initially a 2-min transmission scan was performed for optimal positioning, which was then checked during the study by a cross-shaped low-power laser beam and pen markers on the skin. Movements were minimised by fastening a Velcro strap over the chest.

Analysis of the PET studies for calculation of myocardial perfusion

For each frame of the serially acquired data, sets of 35 transaxial images were reconstructed. Each of these image data sets was re-sampled on a work station (General Electric Medical Systems, Milwaukee, WI ) into 12 contiguous short-axis cross-sections of the left ventricle. To generate time-activity curves, six serially acquired short-axis cross-sections (two basal, two mid-ventricular and two apical) were selected in each subject, leaving out the four most apical and the two most basal planes. The definition of the regions of interest (ROI) was the only observer-dependent part of the analysis; ROIs were assigned onto the last serial image (900 s), in a blinded manner regarding perindoprilat or placebo administration, and copied to the first 16 serially acquired 13N-ammonia images (i.e. the initial 120 s of data after tracer injection) to obtain regional time-activity curves. Rectangular, myocardial ROIs with an area of 64 mm2 were placed corresponding to the anterior, lateral and inferior wall of the left ventricle using a standardised template. The junction of the anterior right ventricular wall with the anterior interventricular septum was used to ensure standardised anatomical location of the template. The septal ROI was omitted in our analysis to reduce the error introduced by dual spill-over from the right and the left ventricular cavities. The time-activity curves from three corresponding sectors in six planes were then averaged. A circular ROI, with an area of approximately 50 mm2, was placed in the centre of the LV blood pool to derive the arterial concentration curve for input function, averaging the input time-activity curves from the three most basal planes. We corrected for partial volume effects with an individually estimated recovery coefficient taking into account the image FWHM, the ROI width and the values of the subject’s LV free wall thickness. The corrected time-activity curves were then fitted with a two-compartment tracer kinetic model.

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Hesse, B., Meyer, C., Nielsen, F.S. et al. Myocardial perfusion in type 2 diabetes with left ventricular hypertrophy: normalisation by acute angiotensin-converting enzyme inhibition. Eur J Nucl Med Mol Imaging 31, 362–368 (2004). https://doi.org/10.1007/s00259-003-1388-6

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  • DOI: https://doi.org/10.1007/s00259-003-1388-6

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