SLICC/ACR damage index independently associated with left ventricular diastolic dysfunction in patients with systemic lupus erythematosus.

Left ventricular (LV) diastolic dysfunction has been reported in both active and inactive systemic lupus erythematosus (SLE) patients without clinical evidence of cardiovascular disease. However, the relationship between the long-term inflammatory burden reflected by the SLICC/ACR damage index and LV diastolic function has not been studied. Eighty-two SLE patients and 82 controls matched for age, sex, body mass index, blood pressure and heart rate underwent echocardiography with tissue Doppler imaging (TDI). LV diastolic function was estimated by the myocardial early diastolic velocity (E') at the lateral annulus. There were 51 patients (62.2%) with nephritis, 23 patients (28.0%) with hypertension, 21 patients (25.6%) with vasculitis, 16 patients (19.5%) with pulmonary hypertension, 4 patients (4.9%) with cerebrovascular disease and 2 patients (2.4%) with diabetes mellitus. Sixty-two patients (75.6%) were taking prednisone and 35 patients (42.7%) used a immunosuppressant. Forty-five patients (54.8%) had active disease and suffered from disease-related end-organ damage. Patients with SLICC/ACR damage index ≥1 had more evidence of LV diastolic dysfunction with lower lateral annulus E' (9.6 ± 3.4 vs 12.9 ± 3.5 cm/s, p < 0.001) than those without. In addition, the proportion of patients with abnormal LV myocardial relaxation (defined as lateral E' < 10.0 cm/s) (51.1% vs 16.2%, χ(2) = 10.8, p = 0.001) were significantly higher. Multivariate analysis showed that the SLICC/ACR damage index ≥1 was independently associated with LV diastolic dysfunction (OR = 3.80, 95%CI: 1.21-11.95, p = 0.023) after adjusting for hypertension, disease duration and medical therapy. This may suggest that the overall inflammatory burden in SLE, as reflected by SLICC/ACR damage index, is associated with the development of diastolic dysfunction in SLE patients.

Reduced left atrial function on exercise in patients with heart failure and normal ejection fraction.

AIMS: The cardinal symptom of heart failure with a normal ejection fraction (HFNEF) is exertional dyspnoea. The authors hypothesised that failure of left atrial (LA) compensatory mechanism particularly on exercise contributes to the genesis of symptoms in HFNEF patients. METHODS AND RESULTS: Fifty HFNEF patients, 15 asymptomatic hypertensive subjects and 30 healthy controls underwent rest and submaximal exercise echocardiography. Rest and exercise systolic, early diastolic and late diastolic (Am) mitral annular velocities were assessed using colour tissue Doppler echocardiography. Left atrial functional reserve index was calculated. Am at rest was comparable between all three groups, but exercise Am was significantly lower in HFNEF compared with hypertensive subjects and healthy controls resulting in a lower LA functional reserve index (0.84 (1.34) vs 2.39 (1.27) and 1.81 (1.39), p<0.001). LA volume index was significantly higher in HFNEF patients (30.4 (9.2) vs 27.9 (6.3) and 23.2 (7.1) ml/m(2), p=0.002). There was a significant correlation between Am on exercise with peak VO(2) max (r=0.514, p<0.001) and E/Em on exercise (r=-0.547, p<0.001). Area under the receiver operating characteristic for Am on exercise was 0.768 (95% CI=0.660 to 0.877). CONCLUSION: HFNEF patients have reduced LA function on exercise in addition to left ventricular systolic and diastolic dysfunctions. Reduced LA function probably contributes significantly to exercise intolerance and breathlessness in HFNEF patients.

Potentially modifiable risk factors associated with myocardial infarction in China: the INTERHEART China study.

BACKGROUND: Lifestyle changes associated with the rapidly developing economy increase cardiovascular disease (CVD), myocardial infarction (MI) and cardiovascular risk factors (CVRFs) in China. OBJECTIVE: To assess and compare regionally, and with other regions of the world, distribution of the nine INTERHEART CVRFs, their relationship to MI and the CVD epidemic in China in order to determine how this may influence the future of CVD in China. METHODS: Patients with first acute MI (n = 3030) and age- and sex-matched controls (n = 3056) were enrolled from 26 centres in China. RESULTS: Northern Chinese had higher rates of smoking and hypertension, whereas southern Chinese reported lower fruit and vegetable intake and higher rates of depression. Compared with other regions, participants from China were older, with lower body mass index and waist to hip ratios, lower total and low-density lipoprotein cholesterol levels, ApoB lipoprotein and ApoB to ApoA-1 ratios, but higher high-density lipoprotein cholesterol and ApoA-1. All nine INTERHEART CVRFs, education and income were significantly associated with MI in the Chinese cohort. There was significant heterogeneity in the strength of association between certain CVRFs and MI for China versus other regions, with stronger associations for the Chinese for diabetes (OR 5.10 vs 2.84), depression (2.27 vs 1.37) and permanent stress (2.67 vs 2.06); and lower for the Chinese for abdominal obesity (1.33 vs 2.62) (p for heterogeneity, all <0.001). CONCLUSIONS: Diabetes and psychosocial factors have strong associations with risk of MI in China, indicating that future increases in these risk factors with societal change in China may hasten rapid increases in CVD.

Hypertension and heart failure: a dysfunction of systole, diastole or both?

The pathological myocardial hypertrophy associated with hypertension contains the seed for further maladaptive development. Increased myocardial oxygen consumption, impaired epicardial coronary perfusion, ventricular fibrosis and remodelling, abnormalities in long-axis function and torsion, cause, to a varying degree, a mixture of systolic and diastolic abnormalities. In addition, chronotropic incompetence and peripheral factors such as lack of vasodilator reserve and reduced arterial compliance further affect cardiac output particularly on exercise. Many of these factors are common to hypertensive heart failure with a normal ejection fraction as well as systolic heart failure. There is increasing evidence that these apparently separate phenotypes are part of a spectrum of heart failure differing only in the degree of ventricular remodelling and volume changes. Furthermore, dichotomizing heart failure into systolic and diastolic clinical entities has led to a paucity of clinical trials of therapies for heart failure with a normal ejection fraction. Therapies aimed at reversing myocardial fibrosis, and targets outside the heart such as enhancing vasodilator reserve and improving chronotropic incompetence deserve further study and may improve the exercise capacity of hypertensive heart failure patients. Hypertension heart disease with heart failure is simply not a dysfunction of systole and diastole. Other peripheral factors including heart rate and vasodilator response with exercise may deserve equal attention in an attempt to develop more effective treatments for this disorder.

The Hong Kong diastolic heart failure study: a randomised controlled trial of diuretics, irbesartan and ramipril on quality of life, exercise capacity, left ventricular global and regional function in heart failure with a normal ejection fraction.

BACKGROUND: Although heart failure with a preserved or normal ejection fraction (HFNEF or diastolic heart failure) is common, treatment outcomes on quality of life and cardiac function are lacking. The effect of renin-angiotensin blockade by irbesartan or ramipril in combination with diuretics on quality of life (QoL), regional and global systolic and diastolic function was assessed in HFNEF patients. METHODS: 150 patients with HFNEF (LVEF >45%) were randomised to (1) diuretics alone, (2) diuretics plus irbesartan, or (3) diuretics plus ramipril. QoL, 6-minute walk test (6MWT) and Doppler echocardiography were performed at baseline, 12, 24 and 52 weeks. RESULTS: The QoL score improved similarly in all three groups by 52 weeks (-46%, 51%, and 50% respectively, all p<0.01), although 6MWT increased only slightly (average +3-6%). Recurrent hospitalisation rates were equal in all groups (10-12% in 1 year). At 1 year, LV dimensions or LVEF had not changed in any group, though both systolic and diastolic blood pressures were lowered in all three groups from 4 weeks onwards. At baseline both mean peak systolic (Sm) and early diastolic (Em) mitral annulus velocities were reduced, and increased slightly in the diuretic plus irbesartan (Sm 4.5 (SEM 0.17) to 4.9 (SEM 0.16) cm/sec; Em 3.8 (SEM 0.25) to 4.2 (SEM 0.25) cm/sec) and ramipril (Sm 4.5 (SEM 0.24) to 4.9 (SEM 0.20) cm/sec; Em 3.3 (SEM 0.25) to 4.04 (SEM 0.32) cm/sec) groups (both p<0.05). NT-pro-BNP levels were raised at baseline (595 (SD 905) pg/ml; range 5-4748) and fell in the irbesartan (-124 (SD 302) pg/ml, p = 0.01) and ramipril (-173 (SD 415) pg/ml, p = 0.03) groups only. CONCLUSIONS: In this typically elderly group of HF patients with normal LVEF, diuretic therapy significantly improved symptoms and neither irbesartan nor ramipril had a significant additional effect. However, diuretics in combination with irbesartan or ramipril marginally improved LV systolic and diastolic longitudinal LV function, and lowered NT-proBNP over 1 year.

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.

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.

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 EFmedian 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 T50%. 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

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.

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.

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.

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.

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

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.

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.