Ethnic differences in cross-sectional associations between impaired glucose regulation, identified by oral glucose tolerance test or HbA1c values, and cardiovascular disease in a cohort of European and South Asian origin.

AIMS: We contrasted impaired glucose regulation (prediabetes) prevalence, defined according to oral glucose tolerance test or HbA1c values, and studied cross-sectional associations between prediabetes and subclinical/clinical cardiovascular disease (CVD) in a cohort of European and South Asian origin. METHODS: For 682 European and 520 South Asian men and women, aged 58-85 years, glycaemic status was determined by oral glucose tolerance test or HbA1c thresholds. Questionnaires, record review, coronary artery calcification scores and cerebral magnetic resonance imaging established clinical plus subclinical coronary heart and cerebrovascular disease. RESULTS: Prediabetes was more prevalent in South Asian participants when defined by HbA1c rather than by oral glucose tolerance test criteria. Accounting for age, sex, smoking, systolic blood pressure, triglycerides and waist-hip ratio, prediabetes was associated with coronary heart disease and cerebrovascular disease in European participants, most obviously when defined by HbA1c rather than by oral glucose tolerance test [odds ratios for HbA1c -defined prediabetes 1.60 (95% CI 1.07, 2.39) for coronary heart disease and 1.57 (95% CI 1.00, 2.51) for cerebrovascular disease]. By contrast, non-significant associations were present between oral glucose tolerance test-defined prediabetes only and coronary heart disease [odds ratio 1.41 (95% CI 0.84, 2.36)] and HbA1c -defined prediabetes only and cerebrovascular disease [odds ratio 1.39 (95% CI 0.69, 2.78)] in South Asian participants. Prediabetes defined by HbA1c or oral glucose tolerance test criteria was associated with cardiovascular disease (defined as coronary heart and/or cerebrovascular disease) in Europeans [odds ratio 1.95 (95% CI 1.31, 2.91) for HbA1c prediabetes criteria] but not in South Asian participants [odds ratio 1.00 (95% CI 0.62, 2.66); ethnicity interaction P = 0.04]. CONCLUSIONS: Prediabetes appeared to be less associated with cardiovascular disease in the South Asian than in the European group. These findings have implications for screening, and early cardiovascular prevention strategies in South Asian populations.

Quantifying the paradoxical effect of higher systolic blood pressure on mortality in chronic heart failure.

BACKGROUND: Although higher blood pressures are generally recognised to be an adverse prognostic marker in risk assessment of cardiology patients, its relationship to risk in chronic heart failure (CHF) may be different. OBJECTIVE: To examine systematically published reports on the relationship between blood pressure and mortality in CHF. METHODS: Medline and Embase were used to identify studies that gave a hazard or relative risk ratio for systolic blood pressure in a stable population with CHF. Included studies were analysed to obtain a unified hazard ratio and quantify the degree of confidence. RESULTS: 10 studies met the inclusion criteria, giving a total population of 8088, with 29 222 person-years of follow-up. All studies showed that a higher systolic blood pressure (SBP) was a favourable prognostic marker in CHF, in contrast to the general population where it is an indicator of poorer prognosis. The decrease in mortality rates associated with a 10 mm Hg higher SBP was 13.0% (95% CI 10.6% to 15.4%) in the heart failure population. This was not related to aetiology, ACE inhibitor or beta blocker use. CONCLUSION: SBP is an easily measured, continuous variable that has a remarkably consistent relationship with mortality within the CHF population. The potential of this simple variable in outpatient assessment of patients with CHF should not be neglected. One possible application of this information is in the optimisation of cardiac resynchronisation devices.

Comparison of temporary bifocal right ventricular pacing and biventricular pacing for heart failure: evaluation by tissue Doppler imaging.

BACKGROUND: The complications and limitations of biventricular pacing largely relate to left ventricular (LV) pacing. An alternative approach was tested of simultaneously pacing the right ventricular (RV) apex and outflow tract (RVOT) or using bifocal right ventricular pacing (BRVP) to provide cardiac resynchronisation. METHODS: 21 consecutive patients with heart failure and severely impaired left ventricular function were studied. Ejection fraction and tissue Doppler data were collected at baseline, during BRVP, and during biventricular pacing, using a temporary pacing protocol. RESULTS: BRVP was achieved in all patients without complication. BRVP significantly reduced mean baseline intra-LV, inter-LV-RV, and global mechanical dyssynchrony from (mean (SD)) 71 (35) to 44 (18) ms, p = 0.003; 86 (42) to 57 (33) ms, p = 0.029; and 157 (67) to 101 (42) ms, p = 0.005, respectively. It increased the ejection fraction from 21 (8)% to 29 (7)%, p = 0.002. Compared with BRVP, reductions in intra-LV, inter-LV-RV, and global mechanical dyssynchrony were superior with biventricular pacing (31 (12) ms, p = 0.014; 36 (27) ms, p = 0.008; and 67 (34) ms, p = 0.01 compared with BRVP, respectively); improvements in ejection fraction were similar (26 (9)%, NS). CONCLUSIONS: In patients with heart failure, superior mechanical resynchronisation is achieved with biventricular pacing compared with BRVP. BRVP may be useful when left ventricular lead placement is not possible.

Platelet and leukocyte activation, atherosclerosis and inflammation in European and South Asian men.

BACKGROUND: Increased platelet activation occurs in ischemic heart disease (IHD), but increased platelet activation is also seen in cerebrovascular atherosclerosis and peripheral artery disease. It is not clear therefore whether platelet activation is an indicator of IHD or a marker of generalized atherosclerosis and inflammation. South Asian subjects are at high risk of IHD, but little is known regarding differences in platelet and leukocyte function between European and South Asian subjects. METHODS: Fifty-four male subjects (age 49-79 years) had coronary artery calcification measured by multislice computed tomography (CT), aortic atherosclerosis assessed by measurement of carotid-femoral pulse wave velocity (aortic PWV), and femoral and carotid atherosclerosis measured by B-mode ultrasound. Platelet and leukocyte activation was assessed by flow cytometry of platelet-monocyte complexes (PMC), platelet expression of PAC-1 binding site and CD62P, and expression of L-selectin on leukocytes. RESULTS: Elevated circulating PMC correlated significantly with elevated aortic PWV and PMC were higher in subjects with femoral plaques. In contrast PMC did not differ by increasing coronary artery calcification category or presence of carotid plaques. Higher numbers of PMC were independently related to elevated levels of C-reactive protein (CRP), higher aortic PWV, hypertension and smoking in a multivariate model. Markers of platelet and leukocyte activation did not differ significantly by ethnicity. CONCLUSIONS: Increased PMC are related to the extent of aortic and femoral atherosclerosis rather than coronary or carotid atherosclerosis. The association between elevated CRP and increased PMC suggests that inflammation in relation to generalized atherosclerosis may play an important role in PMC activation.

The interaction of interventricular pacing intervals and left ventricular lead position during temporary biventricular pacing evaluated by tissue Doppler imaging.

OBJECTIVE: To determine the effects of interventricular pacing interval and left ventricular (LV) pacing site on ventricular dyssynchrony and function at baseline and during biventricular pacing, using tissue Doppler imaging. METHODS: Using an angioplasty wire to pace the left ventricle, 20 patients with heart failure and left bundle branch block underwent temporary biventricular pacing from lateral (n = 20) and inferior (n = 10) LV sites at five interventricular pacing intervals: +80, +40, synchronous, -40, and -80 ms. RESULTS: LV ejection fraction (EF) increased (mean (SD) from 18 (8)% to 26 (10)% (p = 0.016) and global mechanical dyssynchrony decreased from 187 (91) ms to 97 (63) ms (p = 0.0004) with synchronous biventricular pacing compared to unpaced baseline. Sequential pacing with LV preactivation produced incremental improvements in EF and global mechanical dyssynchrony (p<0.0001 and p = 0.0026, respectively), primarily as a result of reductions in inter-LV-RV dyssynchrony (p = 0.0001) rather than intra-LV dyssynchrony (NS). Results of biventricular pacing from an inferior or lateral LV site were comparable (for example, synchronous biventricular pacing, global mechanical dyssynchrony: lateral LV site, 97 (63) ms; inferior LV site, 104 (41) ms (NS); EF: lateral LV site, 26 (10)%; inferior LV site, 27 (10)% (NS)). ECG morphology was identical during biventricular pacing through an angioplasty wire and a permanent lead. CONCLUSIONS: Sequential biventricular pacing with LV preactivation most often optimises LV synchrony and EF. An inferior LV site offers a good alternative to a lateral site. Pacing through an angioplasty wire may be useful in assessing the acute effects of pacing.

Reduced endothelial progenitor cells in European and South Asian men with atherosclerosis.

BACKGROUND: Circulating endothelial progenitor cells (EPCs) play a role in the repair and regeneration of the endothelium and may represent a novel cardiovascular risk factor. South Asian subjects have an increased risk of cardiovascular disease which is not fully explained by known risk factors. This study examined associations of EPCs with atherosclerosis and possible ethnic differences in EPCs. MATERIALS AND METHODS: A population sample of 58 European and South Asian adult men was enriched with the recruitment of an additional 59 European and South Asian men with known coronary disease. The coronary artery calcification score was measured by multi-slice computerized tomography (CT), carotid and femoral intima-media thickness (IMT), and femoral plaques were measured by ultrasound. The subjects were further subdivided into three categories of coronary artery disease on the basis of coronary artery calcification score and clinical history. Total EPCs and non-senescent EPCs (ns-EPCs) were quantified after 5 days cell culture and the number of late outgrowth colonies was measured over a 6-week test period. Circulating CD34+ haematopoietic precursor cells were measured by flow cytometry. RESULTS: Individuals with femoral plaques had reduced total and ns-EPCs. The number of ns-EPCs were reduced in individuals with the most coronary atheroma and were inversely related to the coronary calcification score and femoral IMT. These relationships persisted after multivariate adjustment for other risk factors. The numbers of late outgrowth colonies or circulating CD34+ cells were unrelated to the presence of atherosclerosis. There were no differences in the number of EPCs between European and South Asian subjects. CONCLUSION: The number of EPCs are reduced in subjects with atherosclerosis independent of other risk factors. Reduction in EPC numbers may be an independent risk factor for atherosclerosis but does not explain ethnic differences in cardiovascular risk.

Haemodynamic effects of changes in atrioventricular and interventricular delay in cardiac resynchronisation therapy show a consistent pattern: analysis of shape, magnitude and relative importance of atrioventricular and interventricular delay.

OBJECTIVE: To assess the haemodynamic effect of simultaneously adjusting atrioventricular (AV) and interventricular (VV) delays. METHOD: 35 different combinations of AV and VV delay were tested by using digital photoplethysmography (Finometer) with repeated alternations to measure relative change in systolic blood pressure (SBP(rel)) in 15 patients with cardiac resynchronisation devices for heart failure. RESULTS: Changing AV delay had a larger effect than changing VV delay (range of SBP(rel) 21 v 4.2 mm Hg, p < 0.001). Each had a curvilinear effect. The curve of response to AV delay fitted extremely closely to a parabola (average R2 = 0.99, average residual variance 0.8 mm Hg2). The response to VV delay was significantly less curved (quadratic coefficient 67 v 1194 mm Hg/s2, p = 0.003) and therefore, although the residual variance was equally small (0.8 mm Hg2), the R2 value was 0.7. Reproducibility at two months was good, with the SD of the difference between two measurements of SBP(rel) being 2.5 mm Hg for AV delay (2% of mean systolic blood pressure) and 1.5 mm Hg for VV delay (1% of mean systolic blood pressure). CONCLUSIONS: Changing AV and VV delays results in a curvilinear acute blood pressure response. This shape fits very closely to a parabola, which may be valuable information in developing a streamlined clinical protocol. VV delay adjustment provides an additional, albeit smaller, haemodynamic benefit to AV optimisation.

Arterial pulse wave velocity in coronary arteries.

Pulse wave velocity is related to arterial stiffness. Pulse wave velocity changes with age and disease and is a useful indicator of cardiovascular disease. Different methods are used for evaluating pulse wave velocity in systemic vessels, but none is applicable to coronary arteries. In this study we first compare values of wave speed (c) calculated from measurements of pressure (P) and velocity (U) using different analytical methods: PU-loop, beta stiffness parameter, characteristic impedance, foot-to-foot method, and the sum of squares (Sigma(2)), a novel way of calculating the wave speed (calculated from the square root of the sum of the ratio of the dP(2) and dU(2) over a complete cardiac cycle). Results from human measurements using Doppler ultrasound on carotid arteries show good correlation between the PU-loop method, beta stiffness parameter and Sigma(2). Characteristic impedance calculations show the greatest variation of all methods. The Sigma(2) method was further assessed in vitro for use in coronary vessels. Pressure and velocity measurements were obtained from human coronary arteries following angiographic studies. The measurements were made invasively by co-locating two wires with pressure and velocity transducers. Pressure and velocity data in the left anterior descending, circumflex, left main stem and right coronary arteries were acquired simultaneously along with the ECG signal. Wave speed was calculated using Sigma(2). Wave intensity analysis was used to determine forward and backward traveling waves at different times in different locations, for which wave speed, approximate distance and timings between waves need to be known.

Echocardiographic methods for selecting patients suitable for biventricular pacing therapy.

The large outcome studies of biventricular pacing to date have selected patients using electrocardiogram criteria (prolonged QRS and left bundle branch block morphology). However, 20-30% of patients do not appear to respond clinically, and as a result there has been much interest in developing more specific methods of detecting mechanical dyssynchrony. A number of different echocardiographic techniques have been developed which appear to offer greater sensitivity and specificity than ECG in selecting these patients. This paper reviews the most promising of the echocardiographic techniques and gives guidance for the clinical use of echocardiography in selecting patients for biventricular pacing.

Stress echocardiography for the diagnosis and risk stratification of patients with suspected or known coronary artery disease: a critical appraisal. Supported by the British Society of Echocardiography.

Stress echocardiography today has matured into a robust and reliable technique not only for the diagnosis of suspected coronary artery disease (CAD) but also for the accurate risk stratification of patients with suspected and established CAD. This is mainly because of rapid advances in image acquisition, digital display, and the development of harmonic and contrast imaging. Stress echocardiography today is also utilised in patients with heart failure both for assessing the cause of heart failure and determining the extent of hibernating myocardium. With advances in myocardial perfusion imaging, stress echocardiography now allows simultaneous assessment of myocardial function and perfusion. Tissue Doppler imaging allows quantitation of wall motion. Ready availability and reliability makes stress echocardiography a cost effective technique for the assessment of CAD.

The Coronary Artery Revascularisation in Diabetes (CARDia) trial: background, aims, and design.

BACKGROUND: Patients with diabetes have an increased incidence and severity of ischemic heart disease, which leads to an increased requirement for coronary revascularization. Comparative information regarding mode of revascularization--coronary artery bypass graft surgery surgery (CABG) or percutaneous coronary intervention (PCI)--is limited, mainly confined to a subanalysis of the Bypass Angioplasty Revascularization (BARI) trial, suggesting a mortality benefit of CABG over PCI. No prospective trial has specifically compared these modes of revascularization in patients with diabetes. OBJECTIVE: The Coronary Artery Revascularisation in Diabetes (CARDia) trial is designed to address the hypothesis that optimal PCI is not inferior to modern CABG as a revascularization strategy for diabetics with multivessel or complex single-vessel coronary disease. The primary end point is a composite of death, nonfatal myocardial infarction, and cerebrovascular accident at 1 year. METHOD: A total of 600 patients with diabetes are to be randomized to either PCI or CABG, with few protocol restrictions on operative techniques or use of new technology. This gives a power of 80% to detect non-inferiority of PCI assuming that the PCI 1-year event rate is 9%. A cardiac surgeon and a cardiologist must agree that a patient is suitable for revascularization by either technique prior to recruitment into the study. Twenty-one centers in the United Kingdom and Ireland are recruiting patients. Data on cost effectiveness, quality of life, and neurocognitive function are being collected. Long-term (3-5 year) follow-up data will also be collected.

Selection and optimisation of biventricular pacing: the role of echocardiography.

The quantification of ventricular dyssynchrony is a key factor in identifying patients with severe heart failure who may benefit from cardiac resynchronisation with biventricular pacing (BVP). Echocardiographic techniques appear to offer superior sensitivity and specificity than the ECG in selecting these patients. This paper reviews the scope of current echocardiographic techniques for guiding both patient selection and optimisation of device programming following implantation.

Cardioversion and the use of sedation.

Nurse led cardioversion services have achieved significant reductions in both cost and waiting time. However, the question of safety of the procedure raises several areas of concern.

Physician administered sedation for DC cardioversion.

Providing anaesthetic cover for DC cardioversion can sometimes prove a challenge for the cardiologist, with potentially disastrous consequences for the patient

Anticoagulation for cardioversion of atrial fibrillation.

The cardioversion of chronic atrial fibrillation to sinus rhythm carries a thromboembolic risk of 1.5-6%. These events occasionally occur at the time of cardioversion, but more often happen hours or days later. These strokes and other embolic events may occur even where atrial thrombus has been excluded before cardioversion and it has become apparent that, although atrial electrical activity may be restored by cardioversion, normal mechanical atrial function may take longer to recover. Numerous studies have addressed the role of anticoagulation following cardioversion in patients with atrial fibrillation, however, the mechanism of embolic complications as well as the justification of a standard anticoagulation therapy are not fully established. In this review we will try to present an overview of the mechanisms of thrombosis following cardioversion and give an insight into current anticoagulation strategies.