Stephen J. Gandy

Allopurinol Benefits Left Ventricular Mass and Endothelial Dysfunction in Chronic Kidney Disease

Allopurinol ameliorates endothelial dysfunction and arterial stiffness among patients without chronic kidney disease (CKD), but it is unknown if it has similar effects among patients with CKD. Furthermore, because arterial stiffness increases left ventricular afterload, any allopurinol-induced improvement in arterial compliance might also regress left ventricular hypertrophy (LVH). We conducted a randomized, double-blind, placebo-controlled, parallel-group study in patients with stage 3 CKD and LVH. We randomly assigned 67 subjects to allopurinol at 300 mg/d or placebo for 9 months; 53 patients completed the study. We measured left ventricular mass index (LVMI) with cardiac magnetic resonance imaging (MRI), assessed endothelial function by flow-mediated dilation (FMD) of the brachial artery, and evaluated central arterial stiffness by pulse-wave analysis. Allopurinol significantly reduced LVH (P=0.036), improved endothelial function (P=0.009), and improved the central augmentation index (P=0.015). This study demonstrates that allopurinol can regress left ventricular mass and improve endothelial function among patients with CKD. Because LVH and endothelial dysfunction associate with prognosis, these results call for further trials to examine whether allopurinol reduces cardiovascular events in patients with CKD and LVH.

High-Dose Allopurinol Reduces Left Ventricular Mass in Patients With Ischemic Heart Disease

OBJECTIVES This study sought to ascertain if high-dose allopurinol regresses left ventricular mass (LVM) in patients with ischemic heart disease (IHD). BACKGROUND LV hypertrophy (LVH) is common in patients with IHD including normotensive patients. Allopurinol, a xanthine oxidase inhibitor, has been shown to reduce LV afterload in IHD and may therefore also regress LVH. METHODS A randomized, double-blind, placebo-controlled, parallel group study was conducted in 66 patients with IHD and LVH, comparing 600 mg/day allopurinol versus placebo therapy for 9 months. The primary outcome measure was change in LVM, assessed by cardiac magnetic resonance imaging (CMR). Secondary outcome measures were changes in LV volumes by CMR, changes in endothelial function by flow-mediated dilation (FMD), and arterial stiffness by applanation tonometry. RESULTS Compared to placebo, allopurinol significantly reduced LVM (allopurinol -5.2 ± 5.8 g vs. placebo -1.3 ± 4.48 g; p = 0.007) and LVM index (LVMI) (allopurinol -2.2 ± 2.78 g/m(2) vs. placebo -0.53 ± 2.5 g/m(2); p = 0.023). The absolute mean difference between groups for change in LVM and LVMI was -3.89 g (95% confidence interval: -1.1 to -6.7) and -1.67 g/m(2) (95% confidence interval: -0.23 to -3.1), respectively. Allopurinol also reduced LV end-systolic volume (allopurinol -2.81 ± 7.8 mls vs. placebo +1.3 ± 7.22 mls; p = 0.047), improved FMD (allopurinol +0.82 ± 1.8% vs. placebo -0.69 ± 2.8%; p = 0.017) and augmentation index (allopurinol -2.8 ± 5.1% vs. placebo +0.9 ± 7%; p = 0.02). CONCLUSIONS High-dose allopurinol regresses LVH, reduces LV end-systolic volume, and improves endothelial function in patients with IHD and LVH. This raises the possibility that allopurinol might reduce future cardiovascular events and mortality in these patients. (Does a Drug Allopurinol Reduce Heart Muscle Mass and Improve Blood Vessel Function in Patients With Normal Blood Pressure and Stable Angina?; ISRCTN73579730).

Dynamic MRI contrast enhancement of renal cortex: A functional assessment of renovascular disease in patients with renal artery stenosis

To evaluate differences in the magnitude and time course of renal cortical contrast uptake in patients with minimal, moderate, and severe renal artery stenosis (RAS) using contrast‐enhanced magnetic resonance renography (CE‐MRR).

Vitamin D Therapy to Reduce Blood Pressure and Left Ventricular Hypertrophy in Resistant Hypertension Randomized, Controlled Trial

Low 25-hydroxyvitamin D levels are associated with higher prevalent blood pressure. We tested whether high-dose intermittent oral vitamin D therapy could reduce blood pressure and left ventricular mass in patients with hypertension resistant to conventional treatment. We conducted a parallel-group, double-blind, randomized placebo-controlled trial. Patients with supine office blood pressure >140/90 mm Hg on ≥3 antihypertensive agents received 100 000 U oral vitamin D3 or matching placebo every 2 months. Office and 24-hour ambulatory blood pressure, glucose, and cholesterol were measured at baseline, 2, 4, and 6 months; left ventricular mass index was measured by cardiac MRI on a subgroup at baseline and 6 months. The primary outcome was mean 24-hour ambulatory blood pressure at 6 months. A total of 68 participants were randomized, 34 in each group. Mean age was 63 (SD 11) years, mean baseline office blood pressure was 154/84 (13/10) mm Hg, and mean baseline 25-hydroxyvitamin D level was 42 (16) nmol/L. Treatment with vitamin D did not reduce 24-hour ambulatory blood pressure (adjusted treatment effects: systolic, +3 mm Hg; 95% confidence interval, –4 to +11; P=0.33; diastolic, –2 mm Hg; 95% confidence interval, –6 to +2; P=0.29); similar results were seen for office blood pressure. Left ventricular mass index was measured in a subgroup (n=25); no reduction was seen with vitamin D treatment (adjusted treatment effect, +4 g/m2; 95% confidence interval, 0 to +7; P=0.04). There was no significant change in cholesterol or glucose levels. Thus, 6 months of intermittent, high-dose oral vitamin D3 did not reduce blood pressure or left ventricular mass in patients with resistant hypertension.

Two-dimensional flow quantitative MRI of aortic arch blood flow patterns: Effect of age, sex, and presence of carotid atheromatous disease on prevalence of spiral blood flow.

To determine the effect of age, sex, and presence of carotid atheromatous disease on the presence of aortic spiral blood flow pattern using two‐dimensional flow quantitative magnetic resonance imaging (MRI).

Left Ventricular Noncompaction: Anatomical Phenotype or Distinct Cardiomyopathy?

Background There is considerable overlap between left ventricular noncompaction (LVNC) and other cardiomyopathies. LVNC has been reported in up to 40% of the general population, raising questions about whether it is a distinct pathological entity, a remodeling epiphenomenon, or merely an anatomical phenotype. Objectives The authors determined the prevalence and predictors of LVNC in a healthy population using 4 cardiac magnetic resonance imaging diagnostic criteria. Methods Volunteers >40 years of age (N = 1,651) with no history of cardiovascular disease (CVD), a 10-year risk of CVD < 20%, and a B-type natriuretic peptide level greater than their gender-specific median underwent magnetic resonance imaging scan as part of the TASCFORCE (Tayside Screening for Cardiac Events) study. LVNC ratios were measured on the horizontal and vertical long axis cine sequences. All individuals with a noncompaction ratio of ≥2 underwent short axis systolic and diastolic LVNC ratio measurements, and quantification of noncompacted and compacted myocardial mass ratios. Those who met all 4 criteria were considered to have LVNC. Results Of 1,480 participants analyzed, 219 (14.8%) met ≥1 diagnostic criterion for LVNC, 117 (7.9%) met 2 criteria, 63 (4.3%) met 3 criteria, and 19 (1.3%) met all 4 diagnostic criteria. There was no difference in demographic or allometric measures between those with and without LVNC. Long axis noncompaction ratios were the least specific, with current diagnostic criteria positive in 219 (14.8%), whereas the noncompacted to compacted myocardial mass ratio was the most specific, only being met in 61 (4.4%). Conclusions A significant proportion of an asymptomatic population free from CVD satisfy all currently used cardiac magnetic resonance imaging diagnostic criteria for LVNC, suggesting that those criteria have poor specificity for LVNC, or that LVNC is an anatomical phenotype rather than a distinct cardiomyopathy.

Left ventricular hypertrophy: reduction of blood pressure already in the normal range further regresses left ventricular mass

Objective: Left ventricular hypertrophy (LVH) confers high cardiovascular risk. Regression of LVH reduces risk. Patients with blood pressure in the normal range and LVH are common. We investigated whether further reduction in blood pressure would further regress LVH. Methods: 51 subjects with blood pressure in the normal range and echocardiographic left ventricular hypertrophy were randomly assigned to active treatment (antihypertensive medication) or placebo in a ratio of 2:1. The aim was to maintain office systolic blood pressure at 10 mm Hg less than baseline in the active arm and at baseline level in the placebo arm. Cardiac magnetic resonance imaging was used to measure change in left ventricular mass index over 12 months. Results: 35 subjects completed the study (active 23: placebo 12). Average mean baseline office systolic blood pressure was 122 (SD 9) mm Hg in the active group and 124 (9) mm Hg in the placebo group (p = 0.646). The mean baseline left ventricular mass index was 65.88 (11.87) g/m2 in the active group and 59.16 (11.13) g/m2 in the placebo group (p = 0.114). The mean difference between baseline and end of study office systolic blood pressure was −9.33 (8.56) mm Hg in the active group and −0.08 (9.27) mm Hg in the placebo group (p = 0.007). The mean change in left ventricular mass index was −4.68 (7.31) g/m2 in the active group and +1.97 (6.68) g/m2 in the placebo group (p = 0.014). Conclusions: Reduction in office systolic blood pressure, already in the normal range, of approximately 9 mm Hg, leads to a reduction in left ventricular mass. Further work is required to see if this also leads to a reduction in cardiovascular events. Trial registration number: ISRCTN48331653.

Common carotid intima media thickness and ankle-brachial pressure index correlate with local but not global atheroma burden: a cross sectional study using whole body magnetic resonance angiography.

Background Common carotid intima media thickness (CIMT) and ankle brachial pressure index (ABPI) are used as surrogate marker of atherosclerosis, and have been shown to correlate with arterial stiffness, however their correlation with global atherosclerotic burden has not been previously assessed. We compare CIMT and ABPI with atheroma burden as measured by whole body magnetic resonance angiography (WB-MRA). Methods 50 patients with symptomatic peripheral arterial disease were recruited. CIMT was measured using ultrasound while rest and exercise ABPI were performed. WB-MRA was performed in a 1.5T MRI scanner using 4 volume acquisitions with a divided dose of intravenous gadolinium gadoterate meglumine (Dotarem, Guerbet, FR). The WB-MRA data was divided into 31 anatomical arterial segments with each scored according to degree of luminal narrowing: 0 = normal, 1 = <50%, 2 = 50–70%, 3 = 70–99%, 4 = vessel occlusion. The segment scores were summed and from this a standardized atheroma score was calculated. Results The atherosclerotic burden was high with a standardised atheroma score of 39.5±11. Common CIMT showed a positive correlation with the whole body atheroma score (β 0.32, p = 0.045), however this was due to its strong correlation with the neck and thoracic segments (β 0.42 p = 0.01) with no correlation with the rest of the body. ABPI correlated with the whole body atheroma score (β −0.39, p = 0.012), which was due to a strong correlation with the ilio-femoral vessels with no correlation with the thoracic or neck vessels. On multiple linear regression, no correlation between CIMT and global atheroma burden was present (β 0.13 p = 0.45), while the correlation between ABPI and atheroma burden persisted (β −0.45 p = 0.005). Conclusion ABPI but not CIMT correlates with global atheroma burden as measured by whole body contrast enhanced magnetic resonance angiography in a population with symptomatic peripheral arterial disease. However this is primarily due to a strong correlation with ilio-femoral atheroma burden.

Optimization of the contrast dose and injection rates in whole‐body MR angiography at 3.0T

To optimize the contrast agent dose and delivery rate used in a novel whole‐body magnetic resonance angiography (MRA) protocol using a 3.0T MR scanner.

Technical assessment of whole body angiography and cardiac function within a single MRI examination

Aim To evaluate a combined protocol for simultaneous cardiac MRI (CMR) and contrast-enhanced (CE) whole-body MR angiography (WB-MRA) techniques within a single examination. Materials and methods Asymptomatic volunteers (n = 48) with low-moderate risk of cardiovascular disease (CVD) were recruited. The protocol was divided into four sections: (1) CMR of left ventricle (LV) structure and function; (2) CE-MRA of the head, neck, and thorax followed by the distal lower limbs; (3) CMR LV “late gadolinium enhancement” assessment; and (4) CE-MRA of the abdomen and pelvis followed by the proximal lower limbs. Multiple observers undertook the image analysis. Results For CMR, the mean ejection fraction (EF) was 67.3 ± 4.8% and mean left ventricular mass (LVM) was 100.3 ± 22.8 g. The intra-observer repeatability for EF ranged from 2.1–4.7% and from 9–12 g for LVM. Interobserver repeatability was 8.1% for EF and 19.1 g for LVM. No LV delayed myocardial enhancement was observed. For WB-MRA, some degree of luminal narrowing or stenosis was seen at 3.6% of the vessel segments (involving n = 29 of 48 volunteers) and interobserver radiological opinion was consistent in 96.7% of 1488 vessel segments assessed. Conclusion Combined assessment of WB-MRA and CMR can be undertaken within a single examination on a clinical MRI system. The associated analysis techniques are repeatable and may be suitable for larger-scale cardiovascular MRI studies.