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Biomedical subjects

Alan G Fraser

Publications and source records attributed to Alan G Fraser.

At least 19 recordsLinked to original sources
PubMed2007

Mechanisms of reduction of mitral regurgitation by cardiac resynchronization therapy.

OBJECTIVES: We sought to investigate the effects of improved left ventricular (LV) synchrony on secondary mitral regurgitation in patients receiving cardiac resynchronization therapy for severe heart failure. METHODS: A total of 22 patients, aged 63 +/- 8 years, were studied during sinus rhythm (unpaced), during LV pacing, and during biventricular pacing. Echocardiography was used to assess LV shape, mitral valve morphology and function, and global systolic and diastolic function. Mechanical ventricular synchrony was calculated from regional systolic timings and velocities, using tissue Doppler. RESULTS: Synchronicity index of LV longitudinal function improved from 36 +/- 19 to 14 +/- 8 milliseconds with LV pacing, and from 31 +/- 17 to 12 +/- 7 milliseconds with biventricular pacing (both P < .01). Heterogeneity of myocardial velocities decreased and mean systolic longitudinal velocity increased. Long-axis and short-axis systolic dimensions decreased, and the LV became less spherical. Apical displacement of coaptation from the plane of the mitral annulus, and annular diameter, were reduced. The severity of mitral regurgitation decreased: vena contracta diameter decreased from 5.3 +/- 1.7 to 4.1 +/- 1.5 mm with LV pacing, and from 5.2 +/- 1.7 to 4.0 +/- 1.7 mm with biventricular pacing (both P < .05), correlating with the increase in mean systolic longitudinal velocity (r = -0.49 for LV pacing and r = -0.67 for biventricular pacing, both P < .05). CONCLUSIONS: Cardiac resynchronization reduces mitral regurgitation by improving LV mechanical synchrony, which leads to an increase in LV longitudinal function and a reduction in subvalvar traction.

Analysis of Variance↗
PubMed2006

The future of cardiovascular imaging and non-invasive diagnosis. A joint statement from the European Association of Echocardiography, the Working Groups on Cardiovascular Magnetic Resonance, Computers in Cardiology, and Nuclear Cardiology, of the European Society of Cardiology, the European Association of Nuclear Medicine and the Association for European Paediatric Cardiology.

Advances in medical imaging now make it possible to investigate any patient with cardiovascular disease using multiple methods which vary widely in their technical requirements, benefits, limitations and costs. The appropriate use of alternative tests requires their integration into joint clinical diagnostic services where experts in all methods collaborate. This statement summarises the principles that should guide developments in cardiovascular diagnostic services.

Cardiovascular Diseases↗
PubMed2006

The future of cardiovascular imaging and non-invasive diagnosis: a joint statement from the European Association of Echocardiography, the Working Groups on Cardiovascular Magnetic Resonance, Computers in Cardiology, and Nuclear Cardiology, of the European Society of Cardiology, the European Association of Nuclear Medicine, and the Association for European Paediatric Cardiology.

Advances in medical imaging now make it possible to investigate any patient with cardiovascular disease using multiple methods which vary widely in their technical requirements, benefits, limitations, and costs. The appropriate use of alternative tests requires their integration into joint clinical diagnostic services where experts in all methods collaborate. This statement summarizes the principles that should guide developments in cardiovascular diagnostic services.

Cardiology↗
PubMed2006

Polymorphisms in the organic cation transporter genes SLC22A4 and SLC22A5 and Crohn's disease in a New Zealand Caucasian cohort.

Polymorphisms in the organic cation transporter (OCTN) genes SLC22A4 (OCTN1; polymorphism 1672C/T) and SLC22A5 (OCTN2; polymorphism -207G/C) at the inflammatory bowel disease (IBD) 5 locus comprise a two-allele haplotype (SLC22A-TC) associated with increased risk for Crohn's disease (CD). In this study, we examined the contribution of the disease susceptibility haplotype SLC22A-TC to CD in a New Zealand Caucasian population. The frequencies of the gene polymorphisms 1672C/T and -207G/C were examined in 182 patients with CD and 188 ethnically matched controls by PCR-RFLP analysis. There was a significant difference in the allele frequency (0.444 vs 0.519; P = 0.041) of the 1672T polymorphism in the SLC22A4 gene between controls and patients with CD. In contrast, there was no significant difference (0.497 vs 0.552; P = 0.135) for the -207C polymorphism in the SLC22A5 gene. The homozygote SLC22A-TC diplotype was significantly associated with an increased risk for CD (odds ratio 2.19), and the SLC22A-TC haplotype was associated with increased risk (P = 0.0007) of ileocolonic involvement. The population-attributable risk for the SLC22A-TC haplotype is 15.1%. Thus, SLC22A-TC is associated with an increased risk of CD and disease phenotype in our New Zealand CD cohort.

Cohort Studies↗
PubMed2005

Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment.

BACKGROUND: Chronic heart failure (CHF) is a major cause of morbidity and mortality that requires a novel approach to therapy. Perhexiline is an antianginal drug that augments glucose metabolism by blocking muscle mitochondrial free fatty acid uptake, thereby increasing metabolic efficiency. We assessed the effects of perhexiline treatment in CHF patients. METHODS AND RESULTS: In a double-blind fashion, we randomly assigned patients with optimally medicated CHF to either perhexiline (n=28) or placebo (n=28). The primary end point was peak exercise oxygen consumption (VO2max), an important prognostic marker. In addition, the effect of perhexiline on myocardial function and quality of life was assessed. Quantitative stress echocardiography with tissue Doppler measurements was used to assess regional myocardial function in patients with ischemic CHF. 31P magnetic resonance spectroscopy was used to assess the effect of perhexiline on skeletal muscle energetics in patients with nonischemic CHF. Treatment with perhexiline led to significant improvements in VO2max (16.1+/-0.6 to 18.8+/-1.1 mL . kg(-1) . min(-1); P<0.001), quality of life (Minnesota score reduction from 45+/-5 to 34+/-5; P=0.04), and left ventricular ejection fraction (24+/-1% to 34+/-2%; P<0.001). Perhexiline treatment also increased resting and peak dobutamine stress regional myocardial function (by 15% and 24%, respectively) and normalized skeletal muscle phosphocreatine recovery after exercise. There were no adverse effects during the treatment period. CONCLUSIONS: In patients with CHF, metabolic modulation with perhexiline improved VO2max, left ventricular ejection fraction, symptoms, resting and peak stress myocardial function, and skeletal muscle energetics. Perhexiline may therefore represent a novel treatment for CHF with a good safety profile, provided that the dosage is adjusted according to plasma levels.

Aged↗
PubMed2005

Reduced left ventricular functional reserve in hypertensive patients with preserved function at rest.

In many hypertensive patients, left ventricular pump function is normal at rest but abnormal during exercise. Myocardial dysfunction or altered left ventricular loading may be responsible for this finding. To verify the hypothesis of impaired myocardial functional reserve in the hypertensive heart, we assessed the response of stress-adjusted midwall shortening to graded, low-dose dobutamine infusion in hypertensive subjects with normal midwall shortening at rest. Sixty-five subjects (45 never treated hypertensive subjects and 20 normotensive volunteers comparable for age) received dobutamine at 1, 2, 3, 4, and 5 microg x kg(-1) x min(-1) for 5-minute steps; within this range of infusion rates, heart rate and systemic blood pressure were stable. Two-dimensional, M-mode, and Doppler echocardiography were performed at baseline and at the end of each step. In normotensive controls, midwall shortening increased from baseline during 2 microg x kg(-1) x min(-1) dobutamine by an average of 16+/-4.5% (P<0.01); a value of 2 standard deviations below this mean response was taken as the lower limit of normal. In the hypertensive subjects, 24 had a normal midwall shortening response to dobutamine at this dose (group I) and 21 had a subnormal response (group II). Whereas blood pressure and left ventricular mass were similar in group II and group I, the former had greater relative wall thickness (P<0.01) than the latter. beta-adrenergic stimulation by very-low-dose dobutamine unmasks subtle impairment of myocardial functional reserve in hypertensive subjects with normal myocardial performance at rest. This alteration seems to be related mainly to increase in left ventricular relative wall thickness.

Adrenergic beta-Agonists↗
PubMed2005

Reduced myocardial velocities of left ventricular long-axis contraction identify both systolic and diastolic heart failure-a comparison with brain natriuretic peptide.

BACKGROUND: Echocardiographic diagnosis of radial fractional shortening or global ejection fraction fails to diagnose all patients with heart failure; about 40%, with apparently normal global systolic function, will have elevated brain natriuretic peptide (BNP) concentrations and "pure" diastolic dysfunction. Screening methods do not include assessment of left ventricular (LV) longitudinal function, however, which is a more sensitive marker of subclinical disease. AIMS: We investigated the diagnostic potential of assessment of LV longitudinal function in suspected heart failure, in a comparison against BNP. METHODS: Fifty consecutive subjects (aged 65+/-12 years; 30 men) referred to a heart failure clinic with unexplained breathlessness were examined by echocardiography and had plasma BNP measured by fluorescence immunoassay. RESULTS: Global systolic function (ejection fraction) correlated moderately with log-transformed BNP (r=-0.54), as did global diastolic function (r=0.55 for estimated LV filling pressure, and r=-0.51 for transmitral flow propagation velocity), and radial systolic function (r=-0.60) (all p<0.001). The echocardiographic parameter that correlated best with BNP, however, was LV longitudinal systolic function (r=-0.78, p<0.001). By stepwise multiple regression analysis, BNP was predicted by longitudinal systolic velocity, in association with LV mass index and radial systolic velocity (r=0.81, r(2)=0.66, p<0.0001). The sensitivity and specificity of a longitudinal systolic velocity of </=5.5 cm/s (mean of 4 basal segments) to diagnose heart failure (defined as an elevated BNP) were 94% and 85%, respectively; the negative predictive value was 97%. CONCLUSION: Non-invasive diagnosis or exclusion of suspected heart failure, whether systolic or diastolic, can be performed accurately by echocardiographic measurement of LV longitudinal systolic function.

Aged↗
PubMed2005

"Pure" diastolic dysfunction is associated with long-axis systolic dysfunction. Implications for the diagnosis and classification of heart failure.

AIMS: To investigate regional systolic function of the left ventricle, to test the hypothesis that "pure" diastolic dysfunction (impaired global diastolic filling, with a preserved ejection fraction > or = 50%) is associated with longitudinal systolic dysfunction. METHODS AND RESULTS: One hundred thirty subjects (31 patients with asymptomatic diastolic dysfunction, 30 with diastolic heart failure, 30 with systolic heart failure; and 39 age-matched normal volunteers) were studied by conventional and tissue Doppler echocardiography. Global diastolic function was assessed using the flow propagation velocity, and by estimating left ventricular filling pressure from the ratio of transmitral E and mitral annular E(TDE) velocities (E/E(TDE)); and global systolic function by measurement of ejection fraction. Radial and longitudinal functions were assessed separately from posterior wall and mitral annular velocities. Global and radial systolic function were similar in patients with "pure" diastolic dysfunction and normal subjects, but patients with either asymptomatic diastolic dysfunction or diastolic heart failure had impaired longitudinal systolic function (mean velocities: 8.0+/-1.2 and 7.7+/-1.5 cm/s, respectively, versus 10.1+/-1.5 cm/s in controls; p<0.001). In subjects with normal ejection fraction, global diastolic function correlated with longitudinal systolic function (r=0.56 for flow propagation velocity, and r=-0.53 for E/E(TDE) ratio, both p<0.001), but not with global systolic function. CONCLUSION: Worsening global diastolic dysfunction of the left ventricle is associated with a progressive decline in longitudinal systolic function. Diastolic heart failure as conventionally diagnosed is associated with regional, subendocardial systolic dysfunction that can be revealed by tissue Doppler of long-axis shortening. Diagnostic algorithms and definitions of heart failure need to be revised.

Cross-Sectional Studies↗
PubMed2005

Low utilization and wide interhospital variation in investigation of patients after acute myocardial infarction: inadequate resources or insufficient evidence?

BACKGROUND: Guidelines for the management of patients with acute myocardial infarction are available, but implementation may be difficult when resources are limited. OBJECTIVE: The aim of this study was to investigate whether resources, manpower or access to specialist facilities affect care following myocardial infarction. PATIENTS AND METHODS: A representative sample of 1595 patients in all 19 district general hospitals in Wales was analysed for differences in use of investigations and prescription of secondary prevention and how these factors were related to provision of cardiologists and coronary care beds and distance from specialist cardiac services. RESULTS: Inpatient investigation rates were low and there were wide interhospital variations for exercise testing [mean 42%; interquartile range (IQR) 27-59%] and echocardiography (mean 46%; IQR 33-66%). In comparison, prescription of secondary prevention was similar to European standards and showed less interhospital variation (beta blockers mean 48%; IQR 44-54%; angiotensin-converting enzyme inhibitors mean 59%; IQR 43-63%). There was little association between investigation or secondary prevention rates and cardiac services, but overall rates and provision were low. CONCLUSION: Delivery of care after acute myocardial infarction for stratifying risk and preventing recurrence was unrelated to relative provision or distance from specialist centres. Low use of investigations and high interhospital variability could imply limited access to resources such as echocardiography. Higher rates of prescription of drugs, with less variation between hospitals, argues against low utilization because of insufficient evidence.

Female↗
PubMed2005

Polymorphisms of CARD15/NOD2 and CD14 genes in New Zealand Crohn's disease patients.

Polymorphisms in the CARD15/NOD2 gene, which encodes a cytosolic protein involved in bacterial recognition, are associated with development of Crohn's disease (CD). Other potential susceptibility genes such as CD14 may compound the risk of developing CD. We examined the frequency of the three major CARD15 risk alleles (3020insC/L1007fsinsC, G908R and R702W), and a functional polymorphism (-159C/T) in the promoter of the CD14 gene in 185 CD patients in New Zealand and 187 ethnically matched controls. The frequencies of the 3020insC (8.1 vs 0.8%, P < 0.0001), G908R (3.5 vs 2.4%, P = 0.37) and R702W (7.3 vs 5.1%, P = 0.21) alleles in CD patients and controls, respectively, were similar to those described in Australia, and the ancestral countries of Scotland, Ireland and the UK. Only the 3020insC polymorphism was found to be a significant risk factor for CD in our New Zealand cohort (odds ratio = 10.91 [95% confidence intervals 3.30-36.08]; P < 0.0001 for heterozygotes), but not a single patient was homozygous for the 3020insC polymorphism. The T allele (51 vs 50%, P = 0.77) and TT genotype (26 vs 24%, P = 0.84) frequencies of the -159C/T CD14 gene promoter polymorphism did not significantly differ between CD patients and controls. In summary, our findings provide evidence that the CARD15 3020insC risk allele influences disease susceptibility in a small proportion (<17%) of New Zealand CD patients, whereas there was no evidence that the CD14 -159C/T polymorphism is associated with CD.

Crohn Disease↗
PubMed2005

Regional response of myocardial acceleration during isovolumic contraction during dobutamine stress echocardiography: a color tissue Doppler study and comparison with angiocardiographic findings.

BACKGROUND: Color tissue Doppler imaging permits noninvasive quantitation of regional wall motion. In experimental studies, a new marker, the slope of the isovolumic contraction wave, isovolumic acceleration (IVA) was more insensitive to ventricular loading conditions than myocardial velocities. This study compared the regional response IVA to dobutamine stress echocardiography to angiographic findings. METHODS: The Myocardial Doppler in Stress Echocardiography (MYDISE) study prospectively recruited 149 consecutive patients with chest pain for dobutamine stress tissue Doppler echocardiography prior to coronary angiography. This color tissue Doppler database was analyzed for IVA in 1,192 basal and mid segments at rest and again at peak stress. Angiographic findings were compared to IVA and peak systolic velocities (PSV) in corresponding cardiac segments. The diagnostic accuracy of IVA to predict coronary artery stenosis was determined using cut-off values for three representative segments and with the MYDISE diagnostic model including eight segments. RESULTS: Regional IVA increased in a dose-dependent manner during dobutamine infusion. The response was blunted in the supply territory of stenosed coronary artery branches. IVA performed slightly better than PSV as single marker for coronary artery stenosis. A diagnostic model incorporating IVA and PSV was 85-95% accurate (area under receiver operating characterstic curves). CONCLUSIONS: Regional changes of isovolumic acceleration during dobutamine stress echocardiography reflect regional wall motion and can be used to predict coronary artery stenosis with similar accuracy as a model based on systolic myocardial velocities. As a single marker, IVA performed better than myocardial velocities.

Acceleration↗
PubMed2004

Comparison of left ventricular-biventricular pacing on ventricular synchrony, mitral regurgitation, and global left ventricular function in patients with severe chronic heart failure.

We compared the effects of left ventricular and biventricular pacing in 16 patients (15 men and 1 woman; aged 64 +/- 8 years) with severe heart failure by conventional and tissue Doppler echocardiography. Intraventricular synchrony, regional and global systolic function, diastolic function and filling time, and the severity of secondary mitral regurgitation were similar between left ventricular and biventricular pacing.

Aged↗
PubMed2004

Electrical and mechanical components of dyssynchrony in heart failure patients with normal QRS duration and left bundle-branch block: impact of left and biventricular pacing.

BACKGROUND: Resynchronization pacing is an effective symptomatic treatment for heart failure patients with prolongation of the QRS duration (QRSd). Dyssynchronous contraction of the left ventricle is also observed with normal QRSd. We set out to determine how electrical activation of the left ventricular (LV) free wall differed between patients with left bundle-branch block (LBBB) and normal QRSd and if synchrony improved during pacing in patients with normal QRSd. METHODS AND RESULTS: Twenty-two patients were implanted with resynchronization pacemakers, 13 with LBBB (mean QRS, 171 ms) and 9 with normal QRSd <120 ms (mean, 100 ms). LV lead electrograms and surface ECGs in sinus rhythm (unpaced) were recorded. Conventional and tissue Doppler echocardiography were performed without pacing, with LV and biventricular pacing at optimal atrioventricular delay. Lead electrograms from the LV free wall were later in the LBBB patients in absolute terms (155 ms [SD 23] versus 65.5 ms [SD 25]; P=0.05) and also relative to the surface QRS (90.5% [SD 8] versus 65.5% [SD 24]). Improved synchrony of the left and right ventricles (interventricular synchrony) and of the LV myocardial segments (intraventricular synchrony) was observed for patients with LBBB and normal QRSd. Baseline LV synchrony correlated with timing of LV free-wall electrical activation. Improved intraventricular synchrony during pacing also correlated with LV free-wall electrical activation time. CONCLUSIONS: Resynchronization of systole can be achieved for patients with normal QRSd and LBBB during biventricular and LV pacing. The timing of LV free-wall electrical activation correlated with the improvement in synchrony.

Aged↗
PubMed2004

Subclinical cardiac involvement in myotonic dystrophy manifesting as decreased myocardial Doppler velocities.

To assess subendocardial (long-axis) and mid-wall (short-axis) left ventricular (LV) function in patients with type 1 myotonic dystrophy (MD1), with no symptoms or clinical signs of heart disease, to investigate if they have subclinical cardiac involvement, 28 subjects (14 with MD1, and 14 age- and sex-matched normals) had conventional and tissue Doppler echocardiography. Myocardial velocities and timings to peak systolic contractions were measured. LV wall thickness, diameters, and ejection fraction were not different between the groups. 4/14 of the MD1 patients (29%) had global diastolic dysfunction. Both long-axis and short-axis systolic and early diastolic myocardial velocities were lower in patients with MD1, whereas time-to-peak myocardial contraction was longer; mean longitudinal systolic velocity was 5.5+/-1.7 cm/s in patients with MD1, compared with 7.8+/-1.3 cm/s in normal subjects (P<0.001) 10/14 of the patients (71%) had reduced longitudinal systolic function. Longitudinal systolic and diastolic velocities were inversely related to the duration of the QRS complex ( r=-0.86 and r=-0.63 respectively, both P<0.01), but they did not correlate with the CTG-repeat size. Patients with MD1 have subclinical cardiac impairment revealed by measurement of myocardial velocities using tissue Doppler echocardiography.

Adult↗