Impact of biomarkers for endothelial dysfunction and procoagulant state on 10-year cardiovascular risk in Type 2 diabetes.

AIMS: To estimate the coronary heart disease and cardiovascular disease risk associated with novel biomarkers in Type 2 diabetes mellitus. METHODS: We measured baseline peripheral blood concentrations of soluble E-selectin, factor XIIa, thrombin-antithrombin III complex and plasminogen activator inhibitor-1 in 86 patients with Type 2 diabetes free of known coronary heart disease. We used Cox proportional hazard models to estimate multivariable-adjusted hazard ratios associated with biomarker levels for 10-year coronary heart disease risk (n = 33 events) or total cardiovascular disease risk (n = 45 events). RESULTS: At baseline, mean (sd) age was 62 years (7 years); 62 were men; and 43 had microalbuminuria. Soluble E-selectin demonstrated cross-sectional relationships with glucose and factor XIIa was related to plasminogen activator inhibitor-1 and triglycerides (all P < 0.05). Baseline log soluble E-selectin was significantly related to incident coronary heart disease and cardiovascular disease. Hazard ratios (95% CIs) associated with a 1-unit increase in log soluble E-selectin in age- and sex-adjusted models were: coronary heart disease : 4.6 (95% CI 1.9-11.3), P = 0.001; cardiovascular disease: 3.6 (95% CI 1.7-7.4, P = 0.001); and in multivariable-adjusted models were: coronary heart disease: 2.9 (95% CI 1.2-7.1, P = 0.02); cardiovascular disease: 2.3 (95% CI 1.1-4.8), P = 0.02. Factor XIIa was significantly related to incident cardiovascular disease. The hazard ratios associated with a 1-unit increase in factor XIIa in age- and sex-adjusted models was 1.5 (95% CI 1.1-1.9, P = 0.003) and in a multivariable-adjusted model was 1.3 (95% CI 1.0-1.6, P = 0.047). Plasminogen activator inhibitor-1 and thrombin-antithrombin III complex were not related to cardiovascular disease events. CONCLUSIONS: In our study, soluble E-selectin and factor XIIa were significantly related to 10-year incident macrovascular events in patients with Type 2 diabetes. These preliminary findings call for replication in larger studies.

Delays and adverse clinical outcomes associated with unrecognized pacing indications.

BACKGROUND: A recent UK audit showed that a significant proportion of patients who received pacemakers had pacing indications previously overlooked, leading to significant delays to pacemaker implantation. AIM: To investigate the reasons for, and morbidity associated with, overlooked pacing indications. DESIGN: Prospective observational study in a UK regional pacing centre and its referring district hospitals. METHODS: Hospital records from referring and implanting centres were reviewed for 95 consecutive patients undergoing first pacemaker implant to determine symptoms, investigations and hospitalisations occurring after documentation of a pacing indication. RESULTS: Thirty-three of ninety-five patients (35%) had a pacing indication overlooked, which was Class I in 14 patients and Class IIa in 19. Reasons for not making a pacing referral in these patients included: failure to recognize the indication in 14, making adjustments to potentially culprit medication in 15 and requesting additional 'confirmatory' tests in 4. Twenty-six patients (79%) with missed indications experienced adverse events after documentation of an indication, and before receiving a pacemaker: 23 had ongoing symptoms (including one cardiac arrest), three received temporary pacing wires and 18 were hospitalized with symptoms related to cardiac rhythm. Twenty-seven patients (82%) had a total of 38 additional specialist investigations after documentation of a pacing indication. CONCLUSION: Documentation of an indication for pacing failed to trigger referral for permanent pacing in 35% of patients. This failure led to significant delays, morbidity and use of health service resource, which may have been avoided if timely recognition of the pacing indication had prompted referral. Failure to recognize pacing indications and reassessing symptoms and repeating investigation after changes to medication, often required for the management of associated tachyarrhythmias or other medical conditions, contribute to these delays, perhaps unnecessarily.

The patient journey from symptom onset to pacemaker implantation.

BACKGROUND: Regional variation in permanent pacemaker (PPM) implantation rates is well described, the reasons for which are unclear. Significant delays to PPM implantation in UK practice were described 20 years ago, but contemporary data are lacking. AIM: To investigate delays to PPM implantation and their causes. DESIGN: Prospective observational study in a UK regional pacing centre and its referring district hospitals. METHODS: A total of 95 consecutive patients receiving first PPM implant for bradycardia indications from 1 June 2006 to 31 August 2006 were included. Hospital records from the referring and implanting centres were reviewed to determine the timings of: symptom onset; first hospital contact; documented pacing indication (defined by 2002 ACC/AHA/NASPE guidelines); referral to implanter; and PPM implantation. RESULTS: Forty-eight patients (51%) were referred for pacing urgently; median delay from symptoms to PPM 15 days (range 0-7332 days). Forty-seven patients (49%) were referred electively; median delay from symptoms to PPM 380 days (range 33-7505 days), P < 0.0001. Twenty-three of the 47 elective patients (49%) had previous hospitalization with symptoms suggestive of bradycardia. Thirty-three of the 95 patients (35%) had a Class I or IIa pacing indication which did not trigger a pacing referral. CONCLUSION: There are significant delays to PPM implantation in the United Kingdom, longer in those treated electively than those managed as emergencies. Some delays are due to 'process' problems including waiting lists, but a substantial proportion of patients had delays due to failure to refer for pacing once a pacing indication was documented.

Sudden cardiac death: opportunities for prevention.

The evidence base for implantable cardioverter-defibrillator (ICD) therapy requires expansion of guidance/indications to allow UK physicians to treat a broader range of patients. The ICD clinical consultees to the National Institute for Health and Clinical Excellence (NICE) review current guidance/guidelines, explain the evidence base, and suggest a UK ICD implantation strategy.

The implantable cardioverter-defibrillator: postcode prescribing in the UK 1998-2002.

OBJECTIVE: To determine the rate of implantable cardioverter-defibrillator (ICD) implantation across the UK during the period 1998 to 2002. DESIGN: Observational self reporting with cross checking. SETTING: All ICD implanting centres coordinated by the National Pacemaker and ICD Database. PATIENTS: Every patient receiving an ICD in the UK from 1998 to 2002. MAIN OUTCOME MEASURES: Date of implantation and postcode of each ICD recipient during the study period. RESULTS: ICD implantation increased in the UK in the five year period studied but fell far short of the European average and national targets. Implantation rates varied greatly by region. CONCLUSIONS: The low rate of ICD implantation in the UK and the disparity between regions require further study to determine the barriers to this evidence based treatment.

Individualised quality of life after pacing. Does mode matter?

AIMS: To examine the hypothesis that atrial based pacing improves Quality of Life (QoL) after pacing by undertaking a detailed QoL evaluation that includes an individualised assessment as well as disease specific evaluation. METHODS: Prospective study of patients randomised to VVI(R) or atrial based pacing modes using the Schedule for the Evaluation of Individual QoL (SEIQoL), the 36-item Medical Outcomes Study Short-Form General Health Survey (SF36), and a modified version of the Karolinska Cardiovascular Symptomatology Questionnaire (KCSQ). RESULTS: Seventy-three patients completed the two-year follow up of the study. Pacing improved SEIQoL scores, cardiovascular symptoms and the physical role limitation, social limitation and mental health domains of SF36 from baseline to one month. Pacing mode had no effect on QoL the major determinants of which were baseline QoL and a history of coronary artery disease. CONCLUSION: Atrial based pacing does not improve QoL in the two years after pacing when compared with VVI(R) pacing.

Detection of atrial fibrillation by permanent pacemakers: observations from the STOP AF trial.

Pacemaker telemetry is increasingly being used to infer the presence or absence of arrhythmias in clinical practice. To evaluate the reliability of these data in patients with sick-sinus syndrome, a sub-study of eighteen consecutive patients in the Systematic Trial of Pacing to prevent Atrial Fibrillation (STOP AF) implanted with dual-chamber pacemakers had simultaneous 24-hour Holter recordings and pacemaker telemetry down-loaded. Whilst heart rate data were very similar, telemetry data achieved only 57% sensitivity with 64% specificity for the presence of atrial fibrillation on Holter recording over 24 hours. False-positive results were due to far-field sensing while false-negatives were seen with very short episodes of atrial fibrillation. The pacemaker's anti-tachycardia responses were not specific for the detection of atrial fibrillation. There are very few published reports correlating pacemaker diagnostic data and stored electrograms with external Holter monitoring. We believe that more validation studies of are needed before pacemaker diagnostic data can be used with confidence in clinical practice. It is unlikely that current devices with sophisticated detection algorithms will fail to detect prolonged episodes of arrhythmia and their capacity to confirm events with stored electrograms, intervals and markers reduces the possibility of false-positives, but care must be taken in the interpretation of stored data from devices without these capabilities. Equally, it cannot be assumed that if intracardiac electrograms from one episode confirm the presence of an arrhythmia, that all recorded events have been similarly correctly interpreted. We have shown in a sub-study of STOP-AF that simple mathematical models using heart rate bin analysis are not reliable for detection of arrhythmias with short durations. Despite these limitations, the potential of implanted pacemakers to record cardiac rhythm and trends, such as heart-rate variability, over time remains an exciting prospect, particularly in guiding individual patient therapy.