Treating ST elevation myocardial infarction by primary percutaneous coronary intervention, in-hospital thrombolysis and prehospital thrombolysis. An observational study of timelines and outcomes in 625 patients.

OBJECTIVE: To describe the effects of implementing of a percutaneous coronary intervention (PPCI) service and compare the distribution of reperfusion therapies 12 months pre and post introduction of PPCI. DESIGN: Observational study with data collected 12 months pre and post-availability of Primary PCI as routine treatment. SETTING: Lothian region in South-East Scotland. Patients 625 Patients who received reperfusion treatment between December 2005 and November 2007. RESULTS: PHT was given to 96/328 patients (29%) prior to availability of PPCI as routine treatment. Following routine availability, PPCI was delivered to 248/297 patients who received reperfusion treatment (84%). Median diagnosis-to-PCI balloon inflation time and hospital door-to-balloon time were 84 and 54 min, respectively. Patients received PPCI balloon inflation within 90 min of diagnosis in 60% of cases. PPCI-related delay was 74 min compared with prehospital thrombolysis (PHT). PHT (152 min) and PPCI (166 min) had shorter symptom onset-to-assessment of reperfusion times than in-hospital thrombolysis (IHT) (226 min). CONCLUSIONS: More than two-thirds of the total-ischaemic-time in (ST-segment elevation myocardial infarction) STEMI occurs before the patient reaches hospital, with less than one-third being accounted for by door-to-needle (IHT) or door-to-balloon (PPCI) time. The magnitude of difference in the time between symptom onset-and-assessment of reperfusion treatment efficacy is short and should be considered, particularly in patients treated with thrombolysis in hospitals without cath-lab facilities. Optimal reperfusion treatment including a combination of PHT, IHT and PPCI, as recommended in international guidelines, is feasible in the UK although the balance between the use of different treatments will differ between urban and rural areas.

Effect of moderate walnut consumption on lipid profile, arterial stiffness and platelet activation in humans.

BACKGROUND/OBJECTIVES: A large intake of walnuts may improve lipid profile and endothelial function. The effect of moderate walnut consumption is not known. We investigated whether a moderate intake of walnuts would affect lipid profile, arterial stiffness and platelet activation in healthy volunteers. SUBJECTS/METHODS: A total of 30 healthy males were recruited into a single-blind randomized controlled crossover trial of 4 weeks of dietary walnut supplementation (15 g/day) and 4 weeks of control (no walnuts). Arterial stiffness was assessed using pulse waveform analysis to determine the augmentation index and augmented pressure. Platelet activation was determined using flow cytometry to measure circulating platelet-monocyte aggregates. RESULTS: There were no differences in lipid profile after 4 weeks of walnut supplementation compared with control. Dietary intake of α-linolenic acid was increased during the walnut diet (2.1±0.4 g/day versus 0.7±0.4 g/day, P<0.0001). There were no differences in augmentation index or augmented pressure during walnut supplementation. Walnut supplementation did not affect platelet-monocyte aggregation. CONCLUSIONS: Dietary intervention with a moderate intake of walnuts does not affect lipid profile, arterial stiffness or platelet activation in man. Our results suggest that the potentially beneficial cardiac effects of walnuts may not be apparent at lower and more practical levels of consumption.

Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure.

BACKGROUND: Apelin, the endogenous ligand for the novel G protein-coupled receptor APJ, has major cardiovascular effects in preclinical models. The study objectives were to establish the effects of acute apelin administration on peripheral, cardiac, and systemic hemodynamic variables in healthy volunteers and patients with heart failure. METHODS AND RESULTS: Eighteen patients with New York Heart Association class II to III chronic heart failure, 6 patients undergoing diagnostic coronary angiography, and 26 healthy volunteers participated in a series of randomized, double-blind, placebo-controlled studies. Measurements of forearm blood flow, coronary blood flow, left ventricular pressure, and cardiac output were made by venous occlusion plethysmography, Doppler flow wire and quantitative coronary angiography, pressure wire, and thoracic bioimpedance, respectively. Intrabrachial infusions of (Pyr(1))apelin-13, acetylcholine, and sodium nitroprusside caused forearm vasodilatation in patients and control subjects (all P<0.0001). Vasodilatation to acetylcholine (P=0.01) but not apelin (P=0.3) or sodium nitroprusside (P=0.9) was attenuated in patients with heart failure. Intracoronary bolus of apelin-36 increased coronary blood flow and the maximum rate of rise in left ventricular pressure and reduced peak and end-diastolic left ventricular pressures (all P<0.05). Systemic infusions of (Pyr(1))apelin-13 (30 to 300 nmol/min) increased cardiac index and lowered mean arterial pressure and peripheral vascular resistance in patients and healthy control subjects (all P<0.01) but increased heart rate only in control subjects (P<0.01). CONCLUSIONS: Acute apelin administration in humans causes peripheral and coronary vasodilatation and increases cardiac output. APJ agonism represents a novel potential therapeutic target for patients with heart failure.

Collaborative decision-making between paramedics and CCU nurses based on 12-lead ECG telemetry expedites the delivery of thrombolysis in ST elevation myocardial infarction.

OBJECTIVES: To describe a prehospital thrombolysis (PHT) and expedited inhospital thrombolysis (IHT) programme in south-east Scotland using prehospital 12-lead ECG recordings transmitted by telemetry and autonomous paramedic-administered thrombolysis with decision support being provided by coronary care nurses. DESIGN: Retrospective observational study. SETTING: Three hospitals in south-east Scotland covering a population of 778,468 served by 54 ambulance vehicles. PATIENTS: 11,840 patients who telephoned the ambulance service with "chest pain" over 20 months, during which 812 patients were admitted with ST segment elevation myocardial infarction (STEMI). MAIN OUTCOME MEASURES: All calls and cardiac/potential cardiac calls to the ambulance service, type/time of patient presentation, symptoms/call/door-to-thrombolysis times. RESULTS: Of the 11,840 calls to the ambulance service for chest pain over 20 months of the initiative, 60% were cardiac/potentially cardiac-related by Scottish Ambulance Service triage. ST segment elevation was present in 8% of the 5150 12-lead ECGs transmitted by paramedics to the ECG receiving station in the CCU. Over the 20 months, 812 patients were admitted to the three hospitals with STEMI and 71% received thrombolysis. Median symptom-to-thrombolysis times were 91, 148 and 184 min, respectively, in the PHT, telemetry-facilitated IHT and self-presenting IHT groups. Median call-to-needle time for the PHT group was 40 min. In 2/146 cases the cardiologists judged that the patient should not have been administered PHT. CONCLUSIONS: Based on prehospital 12-lead ECG telemetry, it is possible for paramedics and CCU nurses to conduct live reperfusion decision-making in patients with STEMI, with resultant benefits in symptoms-to-thrombolysis time.

Hospital volume of throughput and periprocedural and medium-term adverse events after percutaneous coronary intervention: retrospective cohort study of all 17,417 procedures undertaken in Scotland, 1997-2003.

OBJECTIVE: To determine whether percutaneous coronary intervention (PCI) hospital volume of throughput is associated with periprocedural and medium-term events, and whether any associations are independent of differences in case mix. DESIGN: Retrospective cohort study of all PCIs undertaken in Scottish National Health Service hospitals over a six-year period. METHODS: All PCIs in Scotland during 1997-2003 were examined. Linkage to administrative databases identified events over two years' follow up. The risk of events by hospital volume at 30 days and two years was compared by using logistic regression and Cox proportional hazards models. RESULTS: Of the 17,417 PCIs, 4900 (28%) were in low-volume hospitals and 3242 (19%) in high-volume hospitals. After adjustment for case mix, there were no significant differences in risk of death or myocardial infarction. Patients treated in high-volume hospitals were less likely to require emergency surgery (adjusted odds ratio 0.18, 95% confidence interval (CI) 0.07 to 0.54, p = 0.002). Over two years, patients in high-volume hospitals were less likely to undergo surgery (adjusted hazard ratio 0.52, 95% CI 0.35 to 0.75, p = 0.001), but this was offset by an increased likelihood of further PCI. There was no net difference in coronary revascularisation or in overall events. CONCLUSION: Death and myocardial infarction were infrequent complications of PCI and did not differ significantly by volume. Emergency surgery was less common in high-volume hospitals. Over two years, patients treated in high-volume centres were as likely to undergo some form of revascularisation but less likely to undergo surgery.

Electrical cardioversion for atrial fibrillation and flutter.

BACKGROUND: Atrial fibrillation increases stroke risk and adversely affects cardiovascular haemodynamics. Electrical cardioversion may, by restoring sinus rhythm, improve cardiovascular haemodynamics, reduce the risk of stroke, and obviate the need for long-term anticoagulation. OBJECTIVES: To assess the effects of electrical cardioversion of atrial fibrillation or flutter on the risk of thromboembolic events, strokes and mortality (primary outcomes), the rate of cognitive decline, quality of life, the use of anticoagulants and the risk of re-hospitalisation (secondary outcomes) in adults (>18 years). SEARCH STRATEGY: We searched the Cochrane CENTRAL Register of Controlled Trials (1967 to May 2004), MEDLINE (1966 to May 2004), Embase (1980 to May 2004), CINAHL (1982 to May 2004), proceedings of the American College of Cardiology (published in Journal of the American College of Cardiology 1983 to 2003), www.trialscentral.org, www.controlled-trials.com and reference lists of articles. We hand-searched the indexes of the Proceedings of the British Cardiac Society published in British Heart Journal (1980 to 1995) and in Heart (1995 to 2002); proceedings of the European Congress of Cardiology and meetings of the Joint Working Groups of the European Society of Cardiology (published in European Heart Journal 1983-2003); scientific sessions of the American Heart Association (published in Circulation 1990-2003). Personal contact was made with experts. SELECTION CRITERIA: Randomised controlled trial or controlled clinical trials of electrical cardioversion plus 'usual care' versus 'usual care' only, where 'usual care' included any combination of anticoagulants, antiplatelet drugs and drugs for 'rate control'. We excluded trials which used pharmacological cardioversion as the first intervention, and trials of new onset atrial fibrillation after cardiac surgery. There were no language restrictions. DATA COLLECTION AND ANALYSIS: For dichotomous data, odds ratios were calculated; and for continuous data, the weighted mean difference was calculated. MAIN RESULTS: We found three completed trials of electrical cardioversion (rhythm control) versus rate control, recruiting a total of 927 participants (Hot Cafe; RACE; STAF) and one ongoing trial (J-RHYTHM). There was no difference in mortality between the two strategies (OR 0.83; CI 0.48 to 1.43). There was a trend towards more strokes in the rhythm control group (OR 1.9; 95% CI 0.99 to 3.64). At follow up, three domains of quality of life (physical functioning, physical role function and vitality) were significantly better in the rhythm control group (RACE 2002; STAF 2003). AUTHORS' CONCLUSIONS: Electrical cardioversion (rhythm control) led to a non-significant increase in stroke risk but improved three domains of quality of life.

Antiplatelet treatment in unstable angina: aspirin, clopidogrel, glycoprotein IIb/IIIa antagonist, or all three?

Evidence on the role of antiplatelet agents in patients with non-ST elevation acute coronary syndrome is reviewed, and a strategy for their use in unstable angina is presented

Electrical cardioversion for atrial fibrillation and flutter.

BACKGROUND: Atrial fibrillation increases the risk of stroke, increases the risk of cognitive impairment, and adversely affects cardiovascular haemodynamics. Electrical cardioversion for atrial fibrillation has been in use since the 1960s; the rationale is that restoration of sinus rhythm improves cardiovascular haemodynamics, reduces the risk of stroke, and obviates the need for long-term anticoagulation. OBJECTIVES: To assess the effects of electrical cardioversion of atrial fibrillation or atrial flutter on the annual risk of thromboembolic events, strokes and mortality (primary outcomes measures), the rate of cognitive decline, quality of life, the use of anticoagulants and the risk of re-hospitalisation (secondary outcome measures) in adults (>18 years) with acute, paroxysmal or sustained atrial fibrillation or atrial flutter, of any duration and any aetiology. SEARCH STRATEGY: One reviewer searched the Cochrane Controlled Clinical Trials Register (2000 Issue 4), MEDLINE (1966 to December 2000), EMBASE (1980 to December 2000), CINAHL (1982 to November 2000) and proceedings of the American College of Cardiology (published in the Journal of the American College of Cardiology 1983 to 2000). Reference lists of articles were searched. Personal contact was made with experts in the field. A second reviewer handsearched proceedings of the British Cardiac Society (published in British Heart Journal (1980 to 1995) and in Heart (1995 to May 2001); proceedings of the European Congress of Cardiology and meetings of the Joint Working Groups of the European Society of Cardiology (published in European Heart Journal 1983-2000); scientific sessions of the American Heart Association (published in Circulation 1990-2000). SELECTION CRITERIA: Randomised controlled trial or controlled clinical trials of electrical cardioversion plus 'usual care' versus 'usual care' only, where 'usual care' included any combination of the following: anticoagulants, antiplatelet drugs and drugs for 'rate control', in adults (>18 years) with acute, paroxysmal or sustained atrial fibrillation or atrial flutter, of any duration and any aetiology. DATA COLLECTION AND ANALYSIS: It was planned to extract study data onto data extraction forms. The planned analysis was by the statistical package in RevMan. MAIN RESULTS: No completed randomised trials or controlled clinical trials of electrical cardioversion were found. Two ongoing trials were identified. REVIEWER'S CONCLUSIONS: There were no data from completed randomised controlled trials or controlled clinical trials to either support or refute the use of electrical cardioversion for atrial fibrillation. Randomised trials of electrical cardioversion are required.

Long-term clinical safety and efficacy of NIROYAL vs. NIR intracoronary stent.

Research in vitro and in animal models suggested that gold electroplating of stents can attenuate neointimal hyperplasia and reduce thrombogenicity. The objective of this study was to evaluate the safety and efficacy of the gold-coated NIROYAL stent in the treatment of stenosed coronary arteries and bypass grafts. We retrospectively studied 181 consecutive patients undergoing deployment of NIR (n = 87) or NIROYAL (n = 94) coronary stents in a single tertiary referral center from July 1997 to December 1998. Mean follow-up duration for the NIR and NIROYAL patient groups were 11.6 and 11.4 (range, 3-12) months, respectively. Stent thrombosis rates were 3/87 (3%) in the NIR and 0/94 (0%) in the NIROYAL group (P = 0.07). The need for target lesion revascularization (TLR) in the NIR patient group was 8/87 (9%) compared to 11/94 (12%) in the NIROYAL patient group (P = 0.6). The overall MACE rates for the NIR and NIROYAL patient groups were 24/87 (28%) and 22/94 (23%), respectively (P = 0.5). The present study, hence, implies equivalence between the stainless steel NIR and the gold-plated NIROYAL stent with no significant difference in immediate and long-term clinical performance profiles.

The impact of QT lag compensation on dynamic assessment of ventricular repolarization: reproducibility and the impact of lead selection.

In cardiac disease, abnormalities exist in the rate-corrected QT interval and the relationship between QT and heart rate. The QT/RR relationship is known to be dynamic and show circadian variation. The availability of automated methods for measurement of QT and RR intervals allows monitoring of the QT/RR relationship and may provide insights into arrhythmia onset. Using a method for analyzing 24-hour recordings that incorporates beat-by-beat QT and RR measurement and an automated mechanism for compensating for lag in adaptation of QT to changes in RR, the authors evaluated the impact of lag compensation on assessment of the QT/RR relationship, reproducibility, and the effect of lead selection in 15 normal subjects. The QT/RR relationship is continuously estimated from the lag compensated data over a 5-minute scrolling time frame. The relationship is expressed as an exponential formula, QT = QTo.RRJ where QTo is the QT interval at a standardized RR interval of 1 second and J is a variable exponent. We found that the use of lag compensation significantly improves the mean 24-hour correlation between QT and RR data (r = 0.87 vs 0.65). The 24-hour mean of QTo and J were highly reproducible (coefficients of variation 2% and 8%, respectively). The mean 24-hour QT/RR relationship for the population was QT = 0.415.(RR)0.32. There was a small difference between leads in QTo and J. Compensating for QT adaptation lag provides a means of assessing the QT/RR relationship over long and short periods. This method allows investigation of the effect of acute interventions on the dynamic QT/RR relationship, which has previously been restricted by the presence of QT hysteresis.

The relationship between QT intervals and mortality in ambulant patients with chronic heart failure. The united kingdom heart failure evaluation and assessment of risk trial (UK-HEART)

AIMS: Mortality in patients with heart failure remains high and is difficult to predict. QT interval parameters on a 12-lead ECG have been shown to predict arrhythmic events in patients with a variety of myocardial diseases. There is some, but not consistent, evidence that QT interval parameters may act as predictors of mortality, in particular sudden death, in patients with heart failure. In an adequately powered prospective study we have studied QT interval parameters in patients with stable chronic heart failure in order to determine whether they are predictive of all-cause mortality or mode of death. METHODS AND RESULTS: Five hundred and fifty-four ambulant outpatients with chronic heart failure were recruited. A 12-lead ECG, chest radiograph, echocardiogram, 24 h ambulatory electrocardiogram and serum for biochemical analysis were obtained at baseline. Patients were followed for 471+/-168 days. QT intervals were measured in all leads blinded to patient's characteristics and outcome, were corrected for heart rate, and the maximum QT intervals, and QT dispersion (range of QT intervals) were determined. The same parameters were determined for JT intervals. The primary end-point was all-cause mortality, secondary end-points were sudden cardiac death and death due to progressive heart failure. Multivariate analysis with the Cox's proportional hazards model was used to determine which variables were independently related to outcome. Four hundred and ninety-five patients had analysable ECGs at study entry and of these 71 died during follow-up. The heart rate corrected QT dispersion and maximum QT interval were significant univariate predictors of all-cause mortality (P=0.026 and <0.0001 respectively), and also of sudden death and progressive heart failure death, but were not related to outcome in the multivariate analysis. The independent predictors of all-cause mortality were cardiothoracic ratio (P=0.0003), creatinine (P=0.0009), heart rate (P=0.007), echocardiographically derived left ventricular end-diastolic dimension (P=0.007) and ventricular couplets on 24 h electrocardiographic monitoring (P=0.015). CONCLUSION: In an adequately powered prospective study none of the QT or JT parameters were shown to be independent predictors of outcome in patients with mild to moderate congestive heart failure. These variables do not therefore add to the prognostic information which can be gained from simple radiographic, biochemical, echocardiographic and Holter data in this group of patients.

Effects of acute angiotensin II type 1 receptor antagonism and angiotensin converting enzyme inhibition on plasma fibrinolytic parameters in patients with heart failure.

BACKGROUND: Angiotensin converting enzyme (ACE) inhibition after myocardial infarction is associated with an improvement in plasma fibrinolytic parameters. The aim of the present study was to determine whether acute ACE inhibition and angiotensin II type 1 (AT1) receptor antagonism have similar effects in patients with heart failure. METHODS AND RESULTS: Twenty patients with moderately severe chronic heart failure received enalapril 10 mg and losartan 50 mg on 2 separate occasions in a single-blind, randomized, crossover design. Plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) antigen and activity were measured at baseline and 6 hours after the dose. Acute administration of losartan but not of enalapril reduced plasma t-PA (11%; P=0.003) and PAI-1 (38%; P<0.001) antigen concentrations, which was associated with increases in t-PA (29%; P=0.03) and decreases in PAI-1 (48%; P=0.01) activity. Changes in plasma fibrinolytic parameters were more marked during losartan treatment (P<0.02), with a 3-fold greater reduction in plasma PAI-1 antigen concentrations (P<0.05). CONCLUSIONS: Acute AT1 antagonism in patients with heart failure is associated with a significant improvement in plasma fibrinolytic parameters that is greater than during ACE inhibition. These beneficial effects of AT1 antagonism and ACE inhibition would therefore appear to be mediated principally through suppression of angiotensin II.

Cardioversion for atrial fibrillation: the views of consultant physicians, geriatricians and cardiologists.

BACKGROUND AND AIMS: Atrial fibrillation (AF) increases the risk of stroke and also has adverse haemodynamic consequences. Cardioversion of AF to sinus rhythm may obviate the need for long-term anticoagulation and improve cardiovascular haemodynamics, but is probably underused. We therefore investigated the views of hospital consultants about cardioversion for AF. METHODS: 336 Postal questionnaires were sent to all 186 consultant physicians, 54 cardiologists and 96 geriatricians in Scotland, followed by one reminder letter to non-responders. RESULTS: 71% Of questionnaires were returned. Cardiologists referred 18% of AF patients for cardioversion, while physicians referred 11% and geriatricians 5%. Cardiologists had better access to cardioversion facilities and were less likely to consider an enlarged left atrium and organic heart disease to be contra-indications to cardioversion. Anticoagulation was given for less than 3 weeks before cardioversion by 9% of cardiologists, 39% of physicians and 65% of geriatricians (P<0.001), and for less than 3 weeks after cardioversion by 17% of cardiologists, 45% of physicians and 47% of geriatricians (P = 0.7). SUMMARY: The wide variation in practice both between and within the different specialties suggests that consensus guidelines based on the best available evidence should be developed.

Excessive morphine requirements after pre-hospital nalbuphine analgesia.

Nalbuphine hydrochloride is an opioid agonist-antagonist that has gained acceptance as a pre-hospital analgesic agent. Nalbuphine has equal analgesic properties to morphine, has a low addiction potential, and can be stored and administered without restrictions, unlike morphine. To date no clinical evidence has been published to support the theoretical difficulty that the action of opioids administered after nalbuphine could be altered or negated. The following case reports highlight 10 patients who received nalbuphine pre-hospital and subsequently required higher doses of opioid analgesia than expected. The discussion summarises the properties of nalbuphine and identifies potential reasons why excessive amounts of opioid analgesia were required.

Regulation of peripheral vascular tone in patients with heart failure: contribution of angiotensin II.

OBJECTIVE: To determine directly the contribution of angiotensin II to basal and sympathetically stimulated peripheral arteriolar tone in patients with heart failure. DESIGN: Parallel group comparison. SUBJECTS: Nine patients with New York Heart Association grade II-IV chronic heart failure, and age and sex matched controls. INTERVENTIONS: Forearm plethysmography, lower body negative pressure, local intra-arterial administration of losartan, angiotensin II, and noradrenaline, and estimation of plasma hormone concentrations. MAIN OUTCOME MEASURES: Forearm blood flow responses, plasma hormone concentrations. RESULTS: Baseline blood pressure, heart rate, and forearm blood flow did not differ between patients and controls. In comparison with the non-infused forearm, losartan did not affect basal forearm blood flow (95% confidence interval -5.5% to +7.3%) or sympathetically stimulated vasoconstriction in controls. However, the mean (SEM) blood flow in patients increased by 13(5)% and 26(7)% in response to 30 and 90 micrograms/min of losartan respectively (p < 0.001). Lower body negative pressure caused a reduction in forearm blood flow of 20(5)% in controls (p = 0.008) and 13(5)% (p = 0.08) in patients (p = 0.007, controls v patients). Blood flow at 90 micrograms/min of losartan correlated with plasma angiotensin II concentration (r = 0.77; p = 0.03). Responses to angiotensin II and noradrenaline did not differ between patients and controls. CONCLUSIONS: Losartan causes acute local peripheral arteriolar vasodilation in patients with heart failure but not in healthy control subjects. Endogenous angiotensin II directly contributes to basal peripheral arteriolar tone in patients with heart failure but does not augment sympathetically stimulated peripheral vascular tone.

A prospective controlled study of the association of Streptococcus bovis with colorectal carcinoma.

AIM: To investigate the ability of Streptococcus bovis to colonise colorectal cancers. PATIENTS: 19 patients with colorectal cancer and 23 controls without malignancy. SETTING: University teaching hospital. METHODS: Prospective study comparing unselected patients with known colorectal cancer with age and sex matched controls. Carcinoma tissue from patients with colorectal cancer and normal colonic mucosa, stool, and blood from both patients and control subjects were cultured. RESULTS: In contrast to published data, the faecal carriage rate was similar in cancer (11%) and control groups (13%). CONCLUSIONS: Faecal colonisation by Str bovis in colorectal cancer patients is lower than previously reported and does not differ significantly from controls.