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Biomedical subjects

D J Pennell

Publications and source records attributed to D J Pennell.

At least 19 recordsLinked to original sources
PubMed2004

Glagov remodeling of the atherosclerotic aorta demonstrated by cardiovascular magnetic resonance: the CORDA asymptomatic subject plaque assessment research (CASPAR) project.

BACKGROUND: Aortic atherosclerosis and coronary artery disease (CAD) are closely linked. Early detection of aortic atherosclerosis with the adoption of appropriate preventive measures may therefore help to reduce mortality and morbidity related to CAD. Arterial remodeling, by which the wall adapts to physiological or pathological insults by a change in vessel size, is being increasingly recognized as an important aspect of atherosclerosis. In this prospective longitudinal study we used cardiovascular magnetic resonance (CMR) to detect aortic plaque and to study aortic wall remodeling in asymptomatic subjects. METHODS: We recruited 175 healthy volunteers (49 years, 110 men) and documented their cardiovascular risk profile. Each subject underwent echocardiogram (ECG)-gated T1-weighted spin-echo imaging of the infrarenal abdominal aorta at baseline and after 2 years. FINDINGS: Of the 175 subjects who volunteered at baseline, CMR was successful in 174 (99%), with one (0.6%) failure due to claustrophobia. At 2 years, follow-up scanning was performed in 169 subjects (97%). Infrarenal aortic plaque was identified at baseline in nine (5.2%) subjects. This was reconfirmed in all nine (100%) cases at 2-year follow-up. No new cases of infrarenal plaque were identified at follow-up. The signal characteristics of the plaque on the subtracted images of the Dixon method indicate that all plaques were fibrous. In the nine subjects with infrarenal plaque, the total plaque burden increased as assessed by the total wall volume (561 to 677 mm3, p = 0.0063). The total vessel volume also increased (1737 to 1835 mm3, p = 0.031) but there was no change in the total luminal volume (1175 to 1157 mm3, p = 0.29). CONCLUSIONS: Cardiovascular magnetic resonance detects subclinical aortic atherosclerosis, can follow plaque burden over time, and confirms the presence of Glagov remodeling with preservation of the lumen despite progression of plaque. Cardiovascular magnetic resonance is well suited for the longitudinal follow-up of the general population with atherosclerosis, may help in the understanding of the natural history of atherosclerosis, and in particular may help determine factors to retard disease progression at an early stage.

Aorta, Abdominal↗
PubMed2004

Non-invasive imaging in the diagnosis and management of Takayasu's arteritis.

OBJECTIVES: Takayasu's arteritis (TA) is a rare disease, in which early diagnosis and assessment of treatment efficacy remain a problem. Signs and symptoms may be non-specific and conventional blood tests unreliable, with vascular inflammation often persisting in the face of a normal acute phase response. The current "gold standard" investigation, x ray angiography, is invasive and only identifies late, structural changes in vessels. Recently, non-invasive imaging methods have shown promise in the assessment of patients with TA. METHODS: The invasive and non-invasive imaging performed on all patients in the rheumatology department at the Hammersmith Hospital between May 1996 and May 2002 who fulfilled the ACR criteria for TA were reviewed. All patients were clinically active at diagnosis and were treated with high dose oral prednisolone and additional oral or intravenous immunosuppression. RESULTS: Non-invasive imaging methods ([(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) and magnetic resonance imaging (MRI)) provided important additional information about disease activity ([(18)F]FDG-PET) and progression of vessel wall thickening (MRI) when compared with x ray angiography. CONCLUSIONS: Non-invasive imaging methods provide useful additional information towards the diagnosis and management of TA. Such techniques may allow earlier diagnosis and more accurate assessment of response to treatment than conventional clinical assessment and/or angiography. Non-invasive imaging is likely to be useful in the management of other large vessel vasculitides.

Adult↗
PubMed2004

Detection of apical hypertrophic cardiomyopathy by cardiovascular magnetic resonance in patients with non-diagnostic echocardiography.

OBJECTIVE: To investigate the role of cardiovascular magnetic resonance (CMR) in a series of patients with ECG repolarisation changes and normal echocardiography. PATIENTS AND DESIGN: 10 patients with anterolateral T wave inversion for which there was no obvious pathological cause who had normal routine echocardiography without contrast for the exclusion of hypertrophic cardiomyopathy (HCM) also had CMR that was diagnostic of apical HCM. RESULTS: Apical HCM detected by CMR could be morphologically severe with wall thickness up to 28 mm, or mild. The extent of repolarisation abnormalities did not correlate to the morphological severity. CONCLUSIONS: In patients with unexplained repolarisation abnormalities, a normal routine echocardiogram without contrast does not exclude apical HCM. Further imaging with CMR or contrast echocardiography may be required. The reliance on routine echocardiography to exclude apical HCM may have led to underreporting of this condition.

Cardiomyopathy, Hypertrophic↗
PubMed2004

Effects of carvedilol on left ventricular remodelling in chronic stable heart failure: a cardiovascular magnetic resonance study.

BACKGROUND: The ability of beta blockers to improve left ventricular function has been demonstrated, but data on the effects on cardiac remodelling are limited. OBJECTIVE: To investigate, using cardiovascular magnetic resonance (CMR), the effects of carvedilol on left ventricular remodelling in patients with chronic stable heart failure and left ventricular systolic dysfunction caused by coronary artery disease. DESIGN: Randomised, double blind, placebo controlled study. SETTING: Chronic stable heart failure. PATIENTS AND INTERVENTION: 34 patients with chronic stable heart failure and left ventricular systolic function taking part in the CHRISTMAS trial (double blind carvedilol v placebo) underwent CMR before randomisation and after six months of treatment. MAIN OUTCOME MEASURE: Left ventricular remodelling at six months. RESULTS: The carvedilol and placebo groups were well balanced at baseline, with no significant intergroup differences. Over the study period, there was a significant reduction in end systolic volume index (ESV(I)) and end diastolic volume index (EDV(I)) between the carvedilol and the placebo group (carvedilol -9 v placebo +3 ml/m2, p = 0.0004; carvedilol -8 v placebo 0 ml/m2, p = 0.05). The ejection fraction increased significantly between the groups (carvedilol +3% v placebo -2%, p = 0.003). CONCLUSIONS: Treatment of chronic stable heart failure with carvedilol results in significant improvement in left ventricular volumes and function. These effects might contribute to the benefits of carvedilol on mortality and morbidity in patients with chronic heart failure.

Adrenergic beta-Antagonists↗
PubMed2004

Late gadolinium enhanced cardiovascular magnetic resonance in Becker muscular dystrophy.

Becker muscular dystrophy is a rare cause of dilated cardiomyopathy. A case of Becker muscular dystrophy is reviewed in which cardiovascular magnetic resonance showed previously unreported findings of extensive mid-myocardial late gadolinium enhancement. Similar detection of late gadolinium enhancement in conjunction with other uses of cardiovascular magnetic resonance may contribute significantly to the diagnosis and management of patients with this unusual and important diagnosis.

Adult↗
PubMed2003

Myocardial viability as a determinant of the ejection fraction response to carvedilol in patients with heart failure (CHRISTMAS trial): randomised controlled trial.

BACKGROUND: The improvement in left-ventricular ejection fraction (LVEF) in response to beta blockers is heterogeneous in patients with heart failure due to ischaemic heart disease, possibly indicating variations in the myocardial substrate underlying left-ventricular dysfunction. We investigated whether improvement in LVEF was associated with the volume of hibernating myocardium (viable myocardium with contractile failure). METHODS: We did a double-blind, randomised trial to compare placebo and carvedilol for 6 months in individuals with stable, chronic heart failure due to ischaemic left-ventricular systolic dysfunction. We enrolled 489 patients, of whom 387 were randomised. Patients were designated hibernators or non-hibernators according to the volume of hibernating myocardium. The primary endpoint was change in LVEF, measured by radionuclide ventriculography, in hibernators versus non-hibernators, on carvedilol compared with placebo. Analysis was by intention to treat. RESULTS: 82 patients dropped out of the study because of adverse events, withdrawal of consent, or failure to complete the investigation. Thus, 305 (79%) were analysed. LVEF was unchanged with placebo (mean change -0.4 [SE 0.9] and -0.4 [0.8] for non-hibernators and hibernators, respectively) but increased with carvedilol (2.5 [0.9] and 3.2 [0.8], respectively; p<0.0001 compared with baseline). Mean placebo-subtracted change in LVEF was 3.2% (95% CI 1.8-4.7; p=0.0001) overall, and 2.9% (0.7-5.1; p=0.011) and 3.6% (1.7-5.4; p=0.0002) in non-hibernators and hibernators, respectively. Effect of hibernator status on response of LVEF to carvedilol was not significant (0.7 [-2.2 to 3.5]; p=0.644). However, patients with more myocardium affected by hibernation or by hibernation and ischaemia had a greater increase in LVEF on carvedilol (p=0.0002 and p=0.009, respectively). INTERPRETATION: Some of the effect of carvedilol on LVEF might be mediated by improved function of hibernating or ischaemic myocardium, or both. Medical treatment might be an important adjunct or alternative to revascularisation for patients with hibernating myocardium.

Adrenergic beta-Antagonists↗
PubMed2003

Differentiation of heart failure related to dilated cardiomyopathy and coronary artery disease using gadolinium-enhanced cardiovascular magnetic resonance.

BACKGROUND: Heart failure treatment depends partly on the underlying cause of the disease. We evaluated cardiovascular magnetic resonance (CMR) for the problem of differentiating dilated cardiomyopathy (DCM) from left ventricular (LV) dysfunction caused by coronary artery disease (CAD). METHODS AND RESULTS: Late gadolinium enhancement with CMR was performed in 90 patients with heart failure and LV systolic dysfunction (63 patients with DCM and unobstructed coronary arteries and 27 with significant CAD at angiography). We also studied 15 control subjects with no coronary risk factors and/or unobstructed coronary arteries. None (0%) of the control subjects had myocardial gadolinium enhancement; however, all patients (100%) with LV dysfunction and CAD had enhancement, which was subendocardial or transmural. In patients with DCM, there were 3 findings: no enhancement (59%); myocardial enhancement indistinguishable from the patients with CAD (13%); and patchy or longitudinal striae of midwall enhancement clearly different from the distribution in patients with CAD (28%). CONCLUSIONS: Gadolinium CMR is a powerful technique to distinguish DCM from LV dysfunction related to CAD and yields new insights in DCM. These data suggest that using the coronary angiogram as the arbiter for the presence of LV dysfunction caused by CAD could have lead to an incorrect assignment of DCM cause in 13% of patients, possibly because of coronary recanalization after infarction. The midwall myocardial enhancement in patients with DCM is similar to the fibrosis found at autopsy; it has not previously been visualized in vivo and warrants further investigation. CMR may become a useful alternative to routine coronary angiography in the diagnostic workup of DCM.

Aged↗
PubMed2003

Tissue Doppler echocardiography in patients with thalassaemia detects early myocardial dysfunction related to myocardial iron overload.

AIMS: To compare an echocardiographic method for detecting abnormal cardiac function before development of overt cardiomyopathy with a recently validated technique of quantifying myocardial iron load. METHODS AND RESULTS: We examined thalassaemia patients whose myocardial iron load had been evaluated with magnetic resonance imaging (MRI). By tissue Doppler echocardiography, myocardial velocities were sampled continuously from base to apex in the RV and LV free wall, and the septum in 52 patients aged 29.2 (14.2-43.1) years and 52 age-matched controls. Ninety-six percent of patients had normal LV ejection fraction by MRI. Thirty-eight (73%) had abnormal iron loading of the myocardium, and 33 of those had regional wall motion abnormalities detected in the septum (n=29), LV (n=2), RV (n=1), and septum plus LV (n=1). The incidence of wall motion abnormalities was significantly higher (P<0.04) in patients with myocardial iron overload (87%) than in the 14 without (35%). Furthermore, myocardial iron overload was suggested by a low T2(*)(15.1+/-15.8 ms) in patients with wall motion abnormalities vs those with normal wall motion (T2(*): 30+/-19 ms) (P<0.007). CONCLUSIONS: Wall motion abnormalities may represent an early sign of cardiac disease despite preserved global function. The regional abnormalities are related to iron overload and easily detectable with tissue Doppler echocardiography.

Adolescent↗
PubMed2003

The heart failure revascularisation trial (HEART): rationale, design and methodology.

BACKGROUND: Most patients with heart failure due to left ventricular systolic dysfunction (LVSD) secondary to coronary artery disease (CAD) have evidence of myocardium in jeopardy (reversible ischaemia and/or stunning hibernation). It is not known whether revascularisation in such cases is safe or beneficial. AIMS: To determine whether revascularisation will improve the survival of patients with LVSD and heart failure secondary to CAD and myocardium in jeopardy. METHODS: This is a randomised controlled trial comparing revascularisation or not, in addition to optimal medical therapy with ACE inhibitors, beta-blockers, aldosterone antagonists and an anti-thrombotic agent. Patients must have heart failure requiring treatment with diuretics, a left ventricular ejection fraction <35% and evidence of coronary disease. Myocardial viability and ischaemia are assessed by a broad range of techniques including stress echocardiography and nuclear imaging. All imaging tests are reviewed in core laboratories to ensure uniform reporting. Any conventional revascularisation technique is permitted. The primary outcome measure is all cause mortality. Symptoms, quality of life and health economic issues will also be explored. Assuming an annual mortality of 10% in the control group and allowing for substantial cross-over rates, a study of 800 patients followed for 5 years has 80% power with an alpha of 0.05 (two-sided) to show a 25% reduction in mortality with revascularisation. RESULTS: At the time of writing 180 patients have been screened for inclusion, 111 have consented to participate and 70 have been randomised. The results of viability testing are awaited in 22 patients. Twenty-six patients had been investigated for myocardial viability and/or by angiography prior to consent, as part of the routine practice in that cardiology department. Of 68 patients who have completed assessment only after consent, 47 (69%) were included. The principal reason for drop-out between consent and randomisation was lack of evidence of myocardial ischaemia or hibernation. CONCLUSION: The HEART trial will help to determine whether investigation of myocardial ischaemia and/or viability with a view to revascularisation should become part of the routine care of patients with heart failure due to LVSD and CAD.

Coronary Artery Disease↗
PubMed2002

Automatic MRI adipose tissue mapping using overlapping mosaics.

This paper presents an automatic method of correcting non-uniform RF coil response for the classification of body composition using MR imaging. By linear mosaic modelling, the smoothly but non-linearly varying bias field, which modulates tissue intensities within the image, was corrected. The overlapping between adjacent mosaics ensured consistent segmentation of body fat content and the effectiveness of the technique was validated by both phantom and in vivo experiments. Ten whole body composition data sets, each with 39 trans-axial slices, were acquired. Automatic segmentation results using the proposed technique were compared with those from manual delineations. The automatic segmentation method was found to be highly accurate and the mean percentage error between the two methods was less than 1.5%.

Adipose Tissue↗
PubMed2001

Incidence, location, pathology, and significance of pulmonary homograft stenosis after the Ross operation.

BACKGROUND: The Ross operation has several theoretical advantages. However, concern exists regarding evolving pathology in the pulmonary homograft. METHODS AND RESULTS: Consecutive patients (n=144; mean age 31 years, range 2 months to 64 years) undergoing the Ross operation were studied between 1993 and 2000. Echocardiographic examination of the pulmonary homograft was performed immediately after surgery, then at yearly intervals for a mean interval of 48 months. Fifteen patients (mean age 37 years) in whom echocardiography revealed peak pulmonary gradients >/=30 mm Hg (mean 46+/-18 mm Hg) underwent MRI with velocity mapping in a Picker 1.5-T magnet. No patient had more than mild pulmonary regurgitation. Four patients required reoperation for rapidly progressive pulmonary homograft stenosis; in all 4, there was macroscopic and microscopic evidence of a pronounced chronic adventitial reaction, with perivascular infiltration producing extrinsic compression. Freedom from any pulmonary homograft stenosis at 7-year follow-up was 79.7%, with instantaneous hazard falling to zero after 4 years. Freedom from reoperation at 7 years was 96.7%. In those studied with MRI, there was evidence of narrowing of the whole homograft or distal suture line in 14 of 15 patients, with obvious excess surrounding tissue in 11. Mean minimum diameter and peak velocity by MRI were 11+/-2 mm and 3.2+/-0.7 m/s, respectively. Multivariate analysis of patient-, surgery-, and homograft-related variables did not reveal any significant risk factors for development of neopulmonary stenosis. CONCLUSIONS: Pulmonary homograft stenosis after the Ross operation is clinically important and appears to represent an early postoperative inflammatory reaction to the pulmonary homograft that leads to extrinsic compression and/or shrinkage.

Adult↗
PubMed2001

Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: a randomized controlled trial with losartan.

BACKGROUND: Local cardiac renin-angiotensin systems may regulate left ventricular (LV) hypertrophic responses. The absence (deletion [D]) of a 287-bp marker in the ACE gene is associated with greater myocardial ACE levels and exercise-related LV growth than is its presence (insertion [I]), an effect potentially mediated through either increased activity of the cellular growth factor angiotensin II on the angiotensin type 1 (AT(1)) receptor or increased degradation of growth-inhibiting kinins. We sought to confirm ACE genotype-associated exertional LV growth and to clarify the role of the AT(1) receptor in this association. METHODS AND RESULTS: One hundred forty-one British Army recruits homozygous for the ACE gene (79 DD and 62 II) were randomized to receive losartan (25 mg/d, a subhypotensive dose inhibiting tissue AT(1) receptors) or placebo throughout a 10-week physical training program. LV mass, determined by cardiac magnetic resonance, increased with training (8.4 g, P:<0.0001 overall; 12.1 versus 4.8 g for DD versus II genotype in the placebo limb, P:=0.022). LV growth was similar in the losartan arm: 11.0 versus 3.7 g for DD versus II genotypes (P:=0.034). When indexed to lean body mass, LV growth in the II subjects was abolished, whereas it remained in the DD subjects (-0.022 versus 0.131 g/kg, respectively; P:=0.0009). CONCLUSIONS: ACE genotype dependence of exercise-induced LV hypertrophy is confirmed. Additionally, LV growth in DD (unlike II) subjects is in excess of the increase in lean body mass. These effects are not influenced by AT(1) receptor antagonism with the use of losartan (25 mg/d). The 2.4-fold greater LV growth in DD men may be due to the effects of angiotensin II on other receptors (eg, angiotensin type 4) or lower degradation of growth-inhibitory kinins.

Adult↗
PubMed2001

Echo-planar magnetic resonance myocardial perfusion imaging: parametric map analysis and comparison with thallium SPECT.

Magnetic resonance (MR) perfusion FLASH imaging has been used for assessing coronary artery disease (CAD). Echo-planar MR techniques have advantages in speed and in making MR perfusion imaging results more clinically accessible through parametric maps, but have not been previously assessed. We implemented a spin-echo, echo-planar MR technique and applied it at rest and during adenosine stress in 26 patients with CAD and abnormal thallium single-photon-emission computed tomography (SPECT), and analyzed the results by using a newly developed parametric map analysis of time to peak, peak intensity, and slope of contrast washin. The results were compared with the results of conventional visual analysis of the perfusion cine series. For detecting abnormal coronary territories, MR and SPECT were comparable for sensitivity, specificity, and accuracy (thallium, 70%, 78%, and 73%; MR, 79% 83%, and 80%; P = NS). There was good agreement between thallium and MR during stress (kappa = 0.49), but defects were larger by MR (2.4 vs. 3.1 segments for slope; P < 0.01). Additional segments were detected at rest by MR (58 for slope vs. 25 for thallium), which correlated with areas that became abnormal with stress in the thallium (sensitivity, 100%; specificity, 63%). The parametric maps were easier and faster to interpret than review of the original first-pass series of images (chi2 = 10.8; P < 0.04). The diagnostic performance of echo-planar perfusion MR and SPECT was similar, and combining the results with parametric mapping was useful for interpretation and considerably improved data display for clinical interpretation. MR, however, was faster and yielded images of higher resolution with no radiation burden. In multislice mode, these new MR techniques may have clinical value.

Aged↗
PubMed2001

Evaluation of free-breathing three-dimensional magnetic resonance coronary angiography with hybrid ordered phase encoding (HOPE) for the detection of proximal coronary artery stenosis.

We evaluated free-breathing, prospective navigator-gated, three-dimensional (3D) magnetic resonance coronary angiography (MRCA) with hybrid ordered phase-encoding (HOPE), in the detection of proximal coronary artery stenosis. The coronary arteries were imaged in 46 patients undergoing cardiac catheterization. The mean scan time was 48 minutes. The mean arterial length (mm) visualized was left main stem (LMS) 11.7 (SD 4.5), left anterior descending (LAD) 30.1 (SD 11.1), circumflex (LCx) 15.5 (SD 8.6), and right (RCA) 56.2 (SD 20.8). Twenty-three patients had coronary artery disease with 47 significant stenoses on cardiac catheterization. All LMS were normal on both catheterization and MRCA. MRCA sensitivity was highest for the LAD (89% CI 65%-99%) and RCA (76% CI 50%-93%), but lower for the LCx (50% CI 21%-79%). Specificity ranged from 72%-100%. Improvements in image quality, length of vessel seen, and specific imaging of the LCx are required for MRCA to become an alternative to cardiac catheterization.

Adult↗