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Biomedical subjects

J E Sanderson

Publications and source records attributed to J E Sanderson.

At least 19 recordsLinked to original sources

Troponin T, left ventricular mass, and function are excellent predictors of cardiovascular congestion in peritoneal dialysis.

Patients on maintenance peritoneal dialysis (PD) are frequently complicated with volume overload. In this study, we sought to evaluate troponin T testing alone or in combination with echocardiographic measures in predicting cardiovascular congestion in PD patients. This was a prospective study of 222 chronic PD patients with echocardiography and measurement of serum troponin T carried out at baseline. Patients were followed for 3 years or until death. The end point was first episode of cardiovascular congestion. Troponin T emerged as an independent predictor of cardiovascular congestion (hazard ratio, 2.98, 95% confidence intervals (CI), 1.19-7.42) in a multivariable Cox regression model, including also left ventricular mass index (LVMi) and ejection fraction (EF). Patients with troponin T>median (0.06 microg/l) and EF median but EF>50% had a 3.10-fold (95% CI, 1.71-5.63) and 1.88-fold (95% CI, 1.05-3.38) adjusted risk of cardiovascular congestion, respectively, than those with troponin T 50%. Patients with troponin T>median and LVMi>or=median (96.23 g/m2.7) had a 2.68-fold (95% CI, 1.39-5.19) adjusted risk of cardiovascular congestion than those with troponin T<or=median and LVMi <median. In conclusion, troponin T predicts cardiovascular congestion in chronic PD patients without acute myocardial ischemia and provides incremental prognostic value for cardiovascular congestion when used in combination with LVM and EF. This easily available parameter adds significant value to echocardiography in identifying PD patients at risk of cardiovascular congestion.

Adult↗

Diastolic heart failure or heart failure with a normal ejection fraction.

Nearly half of patients with symptoms of heart failure are found to have an left ventricular (LV) ejection fraction which is within normal limits. These patients have variously been labeled as having diastolic heart failure, heart failure with preserved LV function or heart failure with normal ejection fraction (HFNEF). Since recent studies have shown that systolic function is not entirely normal in these patients, HFNEF is the better term. More common in elderly females it has a mortality similar to heart failure with a reduced ejection fraction (HFREF). The exact pathophysiology of the symtpoms is still not clear and, therefore, debated. As heart failure is often episodic, the underlying abnormal mechanisms may not be completely apparent at rest. It is likely there is a mixture of systolic and diastolic dysfunction which will be different to some degree in individual patients and isolated diastolic dysfunction or primary abnormalities of relaxation are probably extremely rare. The main difference between HFNEF and HFREF is the degree of ventricular remodeling with increased ventricular volumes in HFREF. The time course of remodeling depends to some extent on the aetiology being quicker post myocardial infarction--the commonest cause of HFREF, and slower with hypertension which is the most frequent aetiological factor in HFNEF. Ventricular volumes rather than ejection fraction or the concept of a pure diastolic abnormality can be used to classify patients in a more rational manner.

Aging↗

Heart failure with a normal ejection fraction.

Nearly half of patients with symptoms of heart failure are found to have a normal left ventricular (LV) ejection fraction. This has variously been labelled as diastolic heart failure, heart failure with preserved LV function or heart failure with a normal ejection fraction (HFNEF). As recent studies have shown that systolic function is not entirely normal in these patients, HFNEF is the preferred term. The epidemiology, aetiology and possible pathophysiology of this contentious condition are reviewed. The importance of the remodelling process in determining whether a patient presents with systolic heart failure or HFNEF is emphasised and this can be used to classify patients in a more rational manner.

Aged↗

Enhanced fusion of myoblasts with myofibers for efficient gene delivery induced by a partially purified protein fraction from rat muscle extract.

The biggest challenge to gene therapy is how to efficiently deliver the desired therapeutic gene into a sufficient number of recipient cells to achieve significant clinical efficacy. Here, we identified a partially purified extract from rat muscle probably containing myoblast specific fusion factor(s) (MSF), which significantly enhanced fusion of donor myoblast with host muscle fibers. Once incorporated, the introduced genetic construct could instruct the machinery of the hybrid cells to express the desired protein(s). Rat satellite cells containing a plasmid carrying a marker bone morphogenetic protein-4 (BMP-4) coding sequence were used as foreign gene delivery vehicle. BrdU labeling of the MSF-pretreated satellite cells allowed tracing the fate of the genetically modified satellite cells in the host muscles. Immunohistochemistry using anti-BMP-4 antibody demonstrated the translation of the introduced gene construct. It was demonstrated that in the presence of MSF, numerous BrdU positive nuclei and the expression of BMP-4 polypeptides could be observed in host hybrid fibers, while in the control group using rat serum to replace MSF containing fraction, only a few BrdU positive signals were detected. The expression of osteocalcin and the elevated alkaline phosphatase activity detected in the hybrid fibers indicated the proper folding, secretion and, post-translational modification of the expressed foreign protein. This strategy of enhanced myoblast-mediated gene transfer would break the major barrier in current practice of normal or engineered myoblast transplantation in the management of genetic muscle diseases or systemic genetic disorders.

Animals↗

Magnetic resonance coronary angiography with 3D TrueFISP: breath-hold versus respiratory gated imaging.

To compare the diagnostic accuracy of coronary magnetic resonance angiography with three-dimensional (3D) trueFISP breath-hold and respiratory gated techniques for the detection of significant coronary artery stenosis. 15 patients who recently underwent elective coronary angiogram were studied and a total of 60 arteries and 48 arteries were assessed by breath-hold and respiratory gated 3D trueFISP techniques, respectively. The image quality, length of artery visualized and the presence or absence of significant coronary artery stenosis were recorded. 83.3% and 81.7% of the arteries obtained with the respiratory gated and the breath-hold techniques, respectively, had an image quality suitable for further analysis. There was no significant difference in the length of artery visualized. Sensitivity and specificity of 80%, 100% and 75% and 100%, respectively, were obtained with the breath-hold and respiratory gated techniques in detecting significant stenosis in the coronary arteries. Both techniques have moderate sensitivity and high specificity in detection of significant stenosis in the visualized segments of the major coronary arteries. However, they cannot replace conventional coronary angiogram for diagnosing coronary artery disease at present. Further studies are required to evaluate whether breath-hold approach is more efficient, therefore should be performed first and respiratory gated approach reserved for those who cannot breath-hold.

Adult↗

A superior early myocardial infarction marker. Human heart-type fatty acid-binding protein.

Human heart-type fatty acid-binding protein (FABP) has a high potential as an early marker for myocardial infarction (MI) being more specific than myoglobin. FABP is a low molecular mass cytoplasmic protein (15 kDa) that is released early after the onset of ischemia and it may be useful for rapid confirmation or exclusion of acute myocardial infarction (AMI). Immunochemically assayed FABP, cardiac troponin I (cTnI) and enzymatically assayed creatine phosphokinase (CPK) were determined serially in plasma and serum samples from 218 patients presenting with chest pain and suspected MI. In the 94 patients with confirmed MI, FABP rose to a maximum level (577.6 +/- 43.8 microg/L) 3 hours after the onset of symptoms and returned to normal within 30 hours. The FABP level peaked 7-9 hours earlier than CPK (2288 +/- 131 U/L) and cTnI (357.1 +/- 23.9 microg/L). CPK took 50-70 hours to return to normal level and cTnI returned to normal level over 70 hours. The areas under the receiver operating characteristic (ROC) curves for FABP were calculated as 0.871 at admission and 0.995 one hour after admission, whereas for CPK the areas were 0.711 and 0.856 and for cTnI the areas were 0.677 and 0.845, indicating that the FABP test gave a better diagnostic classification at the early stage being reached by cTnI (0.995) only 8 hours after admission. For FABP, both sensitivity and negative predictive value (NPV) increased quickly to 100% for samples monitored just one hour after admission. By using only two samples, one at admission and one 1 hour post admission, sequential FABP monitoring can reliably diagnose AMI patients 1 hour after admission and 100% of non-AMI patients can be excluded with no false negative results. The late markers cTnI and CPK have the similar diagnostic performance only 7 hours later. Thus measurement of FABP in plasma or serum allows the earliest immunochemical confirmation or exclusion of AMI.

Adult↗

Variable left ventricular activation pattern in patients with heart failure and left bundle branch block.

OBJECTIVE: To determine the left ventricular (LV) activation pattern in patients with chronic heart failure and left bundle branch block (LBBB) on ECG. DESIGN: Prospective study. SETTING: Tertiary cardiology referral centre in Hong Kong. PATIENTS: Seven patients with LV ejection fraction < 35% and typical LBBB on ECG with QRS duration > or = 130 ms were recruited. Five of them had non-ischaemic dilated cardiomyopathy. METHODS: Non-contact mapping was used to investigate the LV global activation sequences. Tissue Doppler imaging was performed with the LV mapping and correlated with the activation sequences. RESULTS: Three patients had preserved left bundle activation despite LBBB on ECG. Conduction block was detected in four patients during LV activation and the other three had homogeneous depolarisation propagation within the left ventricle. The latest segment of activation was located in either the lateral or the posterior region. Tissue Doppler imaging correlated well with non-contact mapping to locate the conduction block and the latest segment of activation. CONCLUSIONS: LV endocardial activation sequences in patients with chronic heart failure and LBBB are variable. This may have implications for patient selection for treatment with cardiac resynchronisation.

Aged↗

Evidence of atrial mechanical dysfunction by acoustic quantification in abnormal relaxation and restrictive filling patterns of diastolic dysfunction in patients with coronary artery disease.

AIM: This study made use of acoustic quantification (AQ) to investigate if left atrial (LA) mechanical function was impaired in patients with diastolic dysfunction, which might not be detected by conventional Doppler echocardiography. METHODS: One hundred and ten patients with coronary artery disease (mean age 65+/-11 years, 80% male) underwent echocardiography prospectively while AQ was performed using harmonic imaging at the apical four-chamber view to evaluate LA function. RESULTS: By Doppler echocardiography, left ventricular (LV) diastolic dysfunction in the form of abnormal relaxation pattern (ARP) was present in 84, pseudonormal (PN) in nine and restrictive filling pattern (RFP) in 10 patients. LA mechanical dysfunction with impaired total fractional area change (FAC) of </=20% was present in 17/19 (89%) patients in the RFP/PN group, but was observed in 27/84 (32%) patients with ARP. Despite identical diastolic Doppler indices between patients with ARP with preserved (n=57) and impaired total FAC, the latter group had significantly lower LV ejection fraction (P<0.001), larger LV volumes (P<0.05 and 0.002, respectively), as well as larger LA area (P<0.001) and lower LA peak emptying and filling rates (both P=0.001). In contrast, there was no difference in nearly all of the parameters of LA function, LV systolic function and LV volume between patients with RFP/PN and ARP with FAC </=20%. Both active and passive LA pump functions were impaired in patients with RFP/PN or ARP with FAC </=20%. CONCLUSION: LA mechanical dysfunction was found to be present in one-third of the patients with ARP of diastolic dysfunction despite a high MV-A. It was also present in almost all the patients with RFP/PN pattern of diastolic dysfunction. Therefore, AQ may provide information on atrial mechanical function complementary to that of Doppler echocardiography.

Aged↗

High prevalence of left ventricular systolic and diastolic asynchrony in patients with congestive heart failure and normal QRS duration.

OBJECTIVE: To study the possible occurrence of left ventricular (LV) systolic and diastolic asynchrony in patients with systolic heart failure (HF) and narrow QRS complexes. DESIGN: Prospective study. SETTING: University teaching hospital. PATIENTS: 200 subjects were studied by echocardiography. 67 patients had HF and narrow QRS complexes (< or = 120 ms), 45 patients had HF and wide QRS complexes (> 120 ms), and 88 served as normal controls. INTERVENTIONS: Echocardiography with tissue Doppler imaging was performed using a six basal, six mid-segmental model. MAIN OUTCOME MEASURES: Severity and prevalence of systolic and diastolic asynchrony, as assessed by the maximal difference in time to peak myocardial systolic contraction (T(S)) and early diastolic relaxation (T(E)), and the standard deviation of T(S) (T(S)-SD) and of T(E) (T(E)-SD) of the 12 LV segments. RESULTS: The mean (SD) maximal difference in T(S) (controls 53 (23) ms v narrow QRS 107 (54) ms v wide QRS 130 (51) ms, both p < 0.001 v controls) and in T(S)-SD (controls 17.0 (7.8) ms v narrow QRS 33.8 (16.9) ms v wide QRS 42.0 (16.5) ms, both p < 0.001 v controls) was prolonged in the narrow QRS group compared with normal controls. Similarly, the maximal difference in T(E) (controls 59 (19) ms v narrow QRS 104 (71) ms v wide QRS 148 (87) ms, both p < 0.001 v controls) and in T(E)-SD (controls 18.5 (5.8) ms v narrow QRS 33.3 (27.7) ms v wide QRS 48.6 (30.2) ms, both p < 0.001 v controls) was prolonged in the narrow QRS group. The prevalence of systolic and diastolic asynchrony was 51% and 46%, respectively, in the narrow QRS group, and 73% and 69%, respectively, in the wide QRS group. Stepwise multiple regression analysis showed that a low mean myocardial systolic velocity from the six basal LV segments and a large LV end systolic diameter were independent predictors of systolic asynchrony, while a low mean myocardial early diastolic velocity and QRS complex duration were independent predictors of diastolic asynchrony. CONCLUSIONS: LV systolic and diastolic mechanical asynchrony is common in patients with HF with narrow QRS complexes. As QRS complex duration is not a determinant of systolic asynchrony, it implies that assessment of intraventricular synchronicity is probably more important than QRS duration in considering cardiac resynchronisation treatment.

Aged↗

Magnetic resonance imaging in ischaemic heart disease.

Magnetic resonance imaging has an increasing role in the assessment of ischaemic heart disease. Its superb spatial and temporal resolution currently allows accurate assessment of cardiac function, regional wall motion, and the extent of myocardial infarction. Regional myocardial perfusion can also be assessed, most commonly by a first-pass technique. Non-invasive imaging of the coronary arteries by various magnetic resonance imaging techniques represents a major advance in recent years. In the foreseeable future, magnetic resonance imaging may become a single, comprehensive examination for the assessment of ischaemic heart disease.

Coronary Angiography↗

Left ventricular long axis function in diastolic heart failure is reduced in both diastole and systole: time for a redefinition?

OBJECTIVE: To test the hypothesis that, when measured in the long axis, left ventricular systolic function is abnormal in patients with diastolic heart failure. DESIGN: A case-control study. SETTING: University teaching hospital (tertiary referral centre). PATIENTS: 68 patients with heart failure, 29 with a left ventricular ejection fraction (LVEF) of > 0.45 and diastolic dysfunction (diastolic heart failure), 39 with an LVEF of </= 0.45 (systolic heart failure), and 105 normal subjects, including 33 age matched controls. METHODS: LVEF was measured by cross sectional Simpson's method, and mitral annular amplitudes and velocities by M mode and tissue Doppler echocardiography, respectively, along with mitral Doppler inflow velocities. Results were compared between the three groups. MAIN OUTCOME MEASURES: Peak systolic mitral annular velocity and amplitude between the different groups. RESULTS: The mitral annular peak mean velocity and amplitude in systole were lower in the patients with diastolic heart failure (mean (SEM), 4.8 (0.2) cm/s) than in the age matched normal controls (6.1 (0.14) cm/s), but higher than those with systolic heart failure (2.8 (0.13) cm/s) (all p < 0.001). Similar changes were seen the mitral annular amplitude during systole. Peak early diastolic velocity and amplitude were also significantly reduced in the group with diastolic heart failure. Left ventricular hypertrophy was evident in over 95% patients in both diastolic and systolic heart failure groups, with a comparable left ventricular mass index. CONCLUSIONS: In patients with diastolic heart failure and evidence of left ventricular hypertrophy, there is systolic left ventricular impairment as measured by myocardial Doppler imaging of the longitudinal axis. Thus subtle abnormalities of systolic function are present in patients with heart failure and a normal left ventricular ejection fraction, and there appears to be a continuum of systolic function between those with truly normal, mildly impaired (labelled diastolic heart failure), and obviously abnormal left ventricular systolic function. Isolated diastolic dysfunction is uncommon.

Adult↗

The effect of continuous combined hormone replacement therapy on arterial reactivity in postmenopausal women with established angina pectoris.

Most epidemiological studies have suggested that the administration of estrogen reduces cardiovascular risk in healthy postmenopausal women. More recently, however, in the large Heart Estrogen/progestin Replacement Study (HERS), it was unexpectedly found that in women with established cardiovascular disease, there was overall no difference in cardiovascular events between those treated with combined oestrogen/progestin hormone replacement therapy and those on placebo. The aim of this study was to examine the effect of combined hormone replacement therapy on arterial reactivity in women with existing angina pectoris. Seventy-four postmenopausal women with angina pectoris were recruited into a 16 week double-blind, placebo-controlled study of treatment with 2 mg of estradiol combined with 1 mg of norethisterone acetate daily. The median endothelium-dependent change in arterial relaxation increased from 5.00 to 7.69% in the treatment group and decreased from 5.57 to 3.64% in the controls. The median endothelium-independent change in arterial relaxation increased from 6.49 to 7.27% in the treatment group and decreased from 4.39 to 2.07% in the controls. The changes in arterial relaxation between the treatment and control groups were not statistically significant. The administration of estrogen/progestin did not significantly improve either endothelium-dependent or -independent arterial relaxation in postmenopausal women with established cardiovascular disease. We have previously shown that estrogen/progestin treatment improves endothelium dependent relaxation in healthy women. The results of our study provide one possible explanation for the clinical findings of the HERS study. In women with established cardiovascular disease, arterial relaxation does not increase significantly in response to treatment with combined hormone replacement therapy.

Aged↗

Clinical profile of arrhythmogenic right ventricular cardiomyopathy in Chinese patients.

OBJECTIVE: To study the clinical profile of Chinese patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). PATIENTS: Chinese patients who fulfilled the diagnostic criteria of ARVC proposed by the Task Force of the European Society of Cardiology and of the scientific council on cardiomyopathy of the International Society and Federation of Cardiology were recruited for analysis. METHODS: Clinical data of patients with ARVC including age, sex, family history, presenting symptoms, electrocardiograph (ECG), echocardiography, cardiac catheterization, magnetic resonance imaging (MRI), electrophysiology study (EPS) and therapeutic intervention were analyzed. RESULTS: Eleven patients (seven males) were diagnosed with ARVC. Mean age at clinical presentation was 42.6+/-14.8 years. Two patients (18.1%) had positive family history of ARVC or premature sudden cardiac death. The commonest presenting symptoms were palpitation (73%) and dizziness (46%). Spontaneous ventricular tachycardia (VT) was the presenting arrhythmia in 54% and 1 (9%) with ventricular fibrillation and cardiac arrest. Seven patients (64%) had the ECG abnormality as defined by the Task Force. Echocardiography showed right ventricular (RV) dilatation in five patients (46%) and all patients had normal left ventricular function. Nine patients (90%) had RV wall thinning or fibrofatty replacement on MRI examination. Inducible monomorphic VT was detected in four out of nine patients at EPS. All eight patients had normal coronary arteries and left ventriculogram but RV dilatation and global hypokinesia was seen in three patients. Implantable cardioverter defibrillators were implanted in five patients and two of them had shocks delivered during the follow-up period. CONCLUSION: In this study, familial incidence of premature sudden death in patients with ARVC appears to be low and left ventricular involvement in affected individuals is uncommon. MRI is still the best investigation for ARVC.

Adult↗