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Background: Coronary artery bypass graft (CABG) patients are under-represented in acute coronary syndrome (ACS) trials. We compared characteristics and outcomes for patients who did and did not participate in a randomised trial of invasive versus non-invasive management (CABG-ACS)., Methods: ACS patients with prior CABG in four hospitals were randomised to invasive or non-invasive management. Non-randomised patients entered a registry. Primary efficacy (composite of all-cause mortality, rehospitalisation for refractory ischaemia/angina, myocardial infarction (MI), heart failure) and safety outcomes (composite of bleeding, stroke, procedure-related MI, worsening renal function) were independently adjudicated., Results: Of 217 patients screened, 84 (39%) screenfailed, of whom 24 (29%) did not consent and 60 (71%) were ineligible. Of 133 (61%) eligible, 60 (mean±SD age, 71±9 years, 72% male) entered the trial and 73 (age, 72±10 years, 73% male) entered a registry (preferences: physician (79%), patient (38%), both (21%)).Compared with trial participants, registry patients had more valve disease, lower haemoglobin, worse New York Heart Association class and higher frailty.At baseline, invasive management was performed in 52% and 49% trial and registry patients, respectively, of whom 32% and 36% had percutaneous coronary intervention at baseline, respectively (p=0.800). After 2 years follow-up (694 (median, IQR 558-841) days), primary efficacy (43% trial vs 49% registry (HR 1.14, 95% CI 0.69 to 1.89)) and safety outcomes (28% trial vs 22% registry (HR 0.74, 95% CI 0.37 to 1.46)) were similar. EuroQol was lower in registry patients at 1 year., Conclusions: Compared with trial participants, registry participants had excess morbidity, but longer-term outcomes were similar., Trial Registration Number: NCT01895751., Competing Interests: Competing interests: CB is employed by the University of Glasgow, which holds consultancy and/or research agreements with companies that have commercial interests in the diagnosis and treatment of ischaemic heart disease, including Abbott Vascular, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, HeartFlow, Menarini Farmaceutica, Opsens, Philips and Siemens Healthcare. There are no other relevant personal disclosures., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: The benefits of routine invasive management in patients with prior coronary artery bypass grafts presenting with non-ST elevation acute coronary syndromes are uncertain because these patients were excluded from pivotal trials., Methods: In a multicenter trial, non-ST elevation acute coronary syndromes patients with prior coronary artery bypass graft were prospectively screened in 4 acute hospitals. Medically stabilized patients were randomized to invasive management (invasive group) or noninvasive management (medical group). The primary outcome was adherence with the randomized strategy by 30 days. A blinded, independent Clinical Event Committee adjudicated predefined composite outcomes for efficacy (all-cause mortality, rehospitalization for refractory ischemia/angina, myocardial infarction, hospitalization because of heart failure) and safety (major bleeding, stroke, procedure-related myocardial infarction, and worsening renal function)., Results: Two hundred seventeen patients were screened and 60 (mean±SD age, 71±9 years, 72% male) were randomized (invasive group, n=31; medical group, n=29). One-third (n=10) of the participants in the invasive group initially received percutaneous coronary intervention. In the medical group, 1 participant crossed over to invasive management on day 30 but percutaneous coronary intervention was not performed. During 2-years' follow-up (median [interquartile range], 744 [570-853] days), the composite outcome for efficacy occurred in 13 (42%) subjects in the invasive group and 13 (45%) subjects in the medical group. The composite safety outcome occurred in 8 (26%) subjects in the invasive group and 9 (31%) subjects in the medical group. An efficacy or safety outcome occurred in 17 (55%) subjects in the invasive group and 16 (55%) subjects in the medical group. Health status (EuroQol 5 Dimensions) and angina class in each group were similar at 12 months., Conclusions: More than half of the population experienced a serious adverse event. An initial noninvasive management strategy is feasible. A substantive health outcomes trial of invasive versus noninvasive management in non-ST elevation acute coronary syndromes patients with prior coronary artery bypass grafts appears warranted., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01895751.

Background: Rapid access chest pain clinics have facilitated the early diagnosis and treatment of patients with coronary heart disease and angina. Despite this important service provision, coronary heart disease continues to be under-diagnosed and many patients are left untreated and at risk. Recent advances in imaging technology have now led to the widespread use of noninvasive computed tomography, which can be used to measure coronary artery calcium scores and perform coronary angiography in one examination. However, this technology has not been robustly evaluated in its application to the clinic., Methods/design: The SCOT-HEART study is an open parallel group prospective multicentre randomized controlled trial of 4,138 patients attending the rapid access chest pain clinic for evaluation of suspected cardiac chest pain. Following clinical consultation, participants will be approached and randomized 1:1 to receive standard care or standard care plus ≥64-multidetector computed tomography coronary angiography and coronary calcium score. Randomization will be conducted using a web-based system to ensure allocation concealment and will incorporate minimization. The primary endpoint of the study will be the proportion of patients diagnosed with angina pectoris secondary to coronary heart disease at 6 weeks. Secondary endpoints will include the assessment of subsequent symptoms, diagnosis, investigation and treatment. In addition, long-term health outcomes, safety endpoints, such as radiation dose, and health economic endpoints will be assessed. Assuming a clinic rate of 27.0% for the diagnosis of angina pectoris due to coronary heart disease, we will need to recruit 2,069 patients per group to detect an absolute increase of 4.0% in the rate of diagnosis at 80% power and a two-sided P value of 0.05. The SCOT-HEART study is currently recruiting participants and expects to report in 2014., Discussion: This is the first study to look at the implementation of computed tomography in the patient care pathway that is outcome focused. This study will have major implications for the management of patients with cardiovascular disease., Trial Registration: ClinicalTrials.gov Identifier: NCT01149590.

Introduction: Current AHA/ACC guidelines state that junctional rhythm (JR) is an acceptable endpoint in patients undergoing radiofrequency ablation (RFA) for narrow complex tachycardia in the presence of dual AV nodal physiology, but in the absence of inducible AVNRT. Only limited data are available on the utility of JR as a marker of successful slow pathway ablation. We sought to further characterize the sensitivity, specificity, and predictive value of JR in AVNRT ablation., Methods: A retrospective analysis was performed of 387 consecutive patients with documented narrow complex tachycardia referred for ablation, with dual AV nodal physiology and inducible AVNRT at electrophysiological study. RFA of slow pathway was performed, with the presence or absence of JR recorded for each application and inducibility tested using atrial stimulation protocol and isoproterenol., Results: Successful ablation was achieved in 385 of 387 patients using a total of 1,861 applications of radiofrequency energy. JR occurred in 692 applications, giving a sensitivity and specificity of JR as an indicator of successful ablation of 99.5% and 79.1% and a positive predictive value of 55.5%., Conclusions: This study confirms that successful ablation of slow pathway seldom occurs in the absence of JR. Although JR almost invariably occurs with successful ablation, its lack of specificity and low positive predictive value questions the use of it as an endpoint in AVNRT ablations, and the guidelines should reflect this.

This review summarizes the results of placebo-controlled trials of propafenone, a class IC antiarrhythmic drug, in patients with supraventricular tachycardia, atrial fibrillation (AF), and atrial flutter. Success rates for cardioversion from AF or flutter to sinus rhythm of 9-93% have been obtained with intravenous propafenone. The duration of arrhythmia is an important factor in the degree of success. The use of a single oral dose has also been reported to be effective in a number of studies. Several placebo-controlled studies have confirmed the effectiveness of propafenone in the long-term suppression of both suproventricular tachycardia and AF and flutter. These reported trials have shown consistent benefit with propafenone compared with placebo in preventing arrhythmia recurrence. The adverse side effect profile for propafenone has also been reviewed with particular reference to the potential for proarrhythmia. The rate of side effects is dose-dependent and tends to be higher in patients with underlying structural heart disease. Overall propafenone has been shown to be an effective antiarrhythmic drug with an acceptable side effect profile for the acute and long-term treatment of supraventricular arrhythmias.

A 39 year old woman sustained life threatening arrhythmias associated with coronary artery spasm. On both occasions she was attending hospital outpatient clinics and was successfully resuscitated. Electrocardiography performed during further episodes of pain suggested that spasm could occur in either the right or left coronary artery.

Background: Electrocardiography is the fundamental investigation for decision making regarding thrombolytic treatment in acute myocardial infarction (MI). Increasing the accuracy of ECG analysis by input from consultant staff may assist in management decisions in patients with suspected MI., Aims: To evaluate a system whereby out of hours ECGs can be faxed to the consultant to aid in decision making regarding thrombolytic treatment., Methods: 112 patients with suspected MI were assessed on admission by the senior house officer (SHO) who faxed to a cardiology consultant the ECG trace and a predesigned form with information on: clinical assessment of the patient; interpretation of the ECG; and views regarding administration of thrombolytic treatment including choice of agent. The consultant reviewed the information and communicated his views to the SHO. Subsequent diagnosis was recorded in all patients and the forms were analysed in regard to areas of agreement and disagreement between the SHO and the consultant., Results: A diagnosis of MI was confirmed in 52 of the 112 patients (46.4%). The consultant agreed with the SHO's decision on thrombolysis in 98 patients (87.5%). The reason for disagreement in the remaining 14 patients (12.5%) was SHO misinterpretation of the ECG (10 patients) and clinical assessment (four patients). Eight patients were saved unnecessary thrombolytic treatment and four received it when they otherwise would not have. Additionally the choice of thrombolytic agent was changed in six patients from streptokinase to tissue plasminogen activator., Conclusion: The use of fax machine assists in decision making with regard to thrombolytic treatment and provides support to junior doctors in what can be a difficult, yet critical decision.

Head-up tilt testing demonstrates vasovagal mechanisms as a cause for syncope, but the pathophysiology underlying this condition remains unclear. The aim of this study was (i) to measure plasma beta-endorphins, adrenocorticotrophic hormone, cortisol, catecholamines, and brain natriuretic peptide during head-up tilt, and (ii) to assess the effect of naloxone infusion during head-up tilt in subjects with reproducible vasovagal syncope. During the assessment of unexplained syncope, 71 subjects underwent a total of 93 tilt tests (60-70 degrees head upwards for 40-45 min or until syncope occurred) during which frequent blood sampling was performed. Subjects with a positive tilt test (n = 56) (mean duration to syncope 23.6 min) showed a larger rise in beta-endorphin levels prior to syncope (baseline 4.7 +/- 2.2 vs syncope onset 6.9 +/- 3.2 pmol.l-1, P = 0.0001) than those with a negative test (n = 37) (baseline 3.9 +/- 3.9 vs end of test 4.9 +/- 2.3 pmol.l-1, P = 0.03). During tilting, adrenocorticotrophic hormone, cortisol, and noradrenaline increased; adrenaline and brain natriuretic peptide remained unchanged; and these responses were similar in positive and negative test groups. Naloxone (2.6 mg.kg-1 i.v. bolus followed by 20 micrograms.kg-1.min-1 infusion), administered in a double-blind fashion during head-up tilt in nine subjects, failed to modify either the time to syncope or the vasodepressor response. Thus, endogenous opioids appear not to be an important trigger for vasovagal syncope, and other pathophysiological mechanisms should be considered.

A subaortic membrane predisposes to bacterial endocarditis usually affecting the aortic valve and left ventricular outflow tract. Endocarditis involving the subaortic membrane itself has been described twice only; once at operation and once at postmortem. The case of a man with vegetations involving a subaortic membrane that were detected preoperatively and the echocardiographic appearances of these findings are reported.

The class III antiarrhythmic drug dofetilide is known to prolong action potential duration by specific blockade of the delayed rectifier potassium channel Ik. As dofetilide is likely to be used in the treatment of atrial arrhythmias it is important to determine the relative sensitivity of the atrium and ventricle in man. Twelve male patients underwent monophasic action potential and refractory period recordings from the high right atrium and right ventricular septum. The patients received either 8 micrograms.kg-1 dofetilide or placebo intravenously. The mean QTc was prolonged by 11% (SD 5%, P < 0.00001) in the active group; the mean monophasic action potential increased by 31% (SD 15%, P < 0.0005) in the atrium and 27% (SD 9%, P < 0.00005) in the ventricle; the mean effective refractory period increased by 30% (SD 16%, P < 0.0005) in the atrium and 20% (SD 6%, P < 0.0001) in the ventricle. No significant change occurred in the placebo group. There was no significant difference in effect between the two chambers. The change in QTc did not accurately reflect acute changes in refractory period or monophasic action potential duration. This has important implications for the use of QT prolongation to assess the acute effect of class III drugs.

We studied the effects of two active dose levels of dofetilide (8 and 12 micrograms/kg) and placebo in 16 patients with recent onset atrial fibrillation. The study was of a crossover design such that all patients received a therapeutic agent, 15 patients completed the study. Cardioversion was achieved in 2/6 patients receiving 8 micrograms/kg dofetilide and in 2/9 patients receiving 12 micrograms/kg. No patients cardioverted as a result of the placebo infusion. Two patients who cardioverted suffered episodes of torsades de pointes following the active drug. Electrical cardioversion was attempted in eight patients who remained in atrial fibrillation and was successful in six. The average duration of atrial fibrillation was 35 days in those who cardioverted and 83 days in those who did not. The compound appears to have only limited effect in cardioversion of atrial fibrillation of moderate duration.

Objective: To evaluate the influence of pretreatment streptokinase resistance titre and the concentration of IgG antibodies to streptokinase on the efficacy of thrombolytic drugs containing streptokinase in restoring coronary patency in acute myocardial infarction., Design: Comparative observational study., Setting: City general hospital., Patients: One hundred and twenty four previously unexposed patients presenting within six hours of onset of acute myocardial infarction., Interventions: Streptokinase, 1.5 MIU as intravenous infusion over 60 minutes (60 patients), or anistreplase, 30 units as intravenous injection over five minutes (64 patients)., Main Outcome Measures: Pretreatment streptokinase resistance titre and concentration of IgG antibodies to streptokinase were measured in 96 and 124 patients respectively and coronary patency assessed angiographically at 90 minutes and 24 hours., Results: Pretreatment streptokinase resistance titre and concentrations of IgG antibodies to streptokinase were low and skewed towards higher values. Those patients with coronary occlusion at 24 hours had a significantly higher median streptokinase resistance titre (100 v 50 streptokinase IU ml-1, P = 0.02). There were trends towards a higher streptokinase resistance titre in those patients with coronary occlusion at 90 minutes (50 v 20 streptokinase IU ml-1, P = 0.06) and higher concentrations of IgG antibodies to streptokinase in those with coronary occlusion at both 90 minutes and 24 hours (1.53 v 0.925, P = 0.03; 1.65 v 1.04 micrograms streptokinase binding ml-1, P = 0.06). Coronary patency rates were similar in the two treatment groups., Conclusions: In the range measured in previously unexposed patients the streptokinase resistance titre has a small, but significant, negative influence on the efficacy of streptokinase and anistreplase. This effect should be considered if retreatment with streptokinase or anistreplase is proposed.

Background: Endogenous opioids have a tonic inhibitory effect on sympathetic tone and have been implicated in the pathophysiology of vasodepressor syncope. Plasma beta endorphin concentrations increase after vasodepressor syncope induced by exercise or by fasting., Aims: To take frequent samples for plasma beta endorphin estimation during tilt testing, and to determine whether plasma beta endorphin increased before the start of syncope., Patients: 24 patients undergoing tilt testing for investigation of unexplained syncope., Setting: Tertiary referral centre., Methods: Blood samples were obtained during 70 degrees head up tilt testing. Plasma beta endorphin concentrations were estimated by radioimmunoassay (mean(SD) pmol/l)., Results: Patients with a positive test showed a rise in beta endorphin concentrations before syncope (baseline 4.4(1.5) v start of syncope 8.5(3.1), p < 0.002). In contrast, patients with a negative test showed no change in beta endorphin concentrations (baseline 3.4(1.0) v end of test 4.5(2.3), NS). After syncope all patients showed a large secondary increase in beta endorphins (32.3(18.6))., Conclusion: An increase in plasma beta endorphins precedes vasodepressor syncope. This finding supports a pathophysiological role for endogenous opioids.

1. Opioid receptor antagonists such as naloxone have shown antiarrhythmic activity in animal models of coronary artery occlusion. Studies have indicated that these effects are stereospecific but both isomers of naloxone prolong action potential duration and refractoriness in guinea-pig and rabbit isolated ventricular myocardium (Class III effect). 2. This study was performed to identify whether this Class III effect of naloxone could be reproduced in human myocardium in vivo. Twenty patients with coronary artery disease received intravenous racemic naloxone (1-40 micrograms kg-1 min-1). Surface electrocardiographic parameters were measured and refractory periods were determined during fixed rate pacing by programmed stimulation. 3. The corrected QT interval during sinus rhythm (SR-QTc) was prolonged by 5(3)% (P = 0.06) at a dose of 20 micrograms kg-1 min-1 and by 9(10)% at 40 micrograms kg-1 min-1 (P = 0.03). These small changes were lost at higher paced heart rates. No significant effects on atrial, atrioventricular nodal or ventricular refractoriness were seen. 4. Plasma naloxone concentrations well into the micromolar range were achieved with both of the higher doses of naloxone administered. Plasma beta-endorphin concentrations invariably increased following naloxone infusion. There was no statistical relationship between peak plasma naloxone concentrations and the absolute or percent prolongation of SR-QTc. 5. It seems unlikely that racemic naloxone would have any clinical utility as an antiarrhythmic agent. Racemic naloxone may enhance cardiac adrenergic nerve activity and this receptor mediated effect may have prevented the demonstration of any nonreceptor mediated prolongation of cardiac refractoriness. Studies with the individual stereoisomers of naloxone would be of interest.

Objective: To assess the clinical ability of general practitioners to decide to give thrombolytic therapy to patients with suspected myocardial infarction and to assess the contribution of the electrocardiograph (ECG) to this decision-making process., Setting: 7 practices on the North side of Glasgow and the coronary care unit of Stobhill General Hospital., Subjects: 137 patients presenting with chest pain who required direct admission to the coronary care unit., Main Outcome Measures: Agreement between the general practitioner's clinical decision to give thrombolytic therapy with or without reference to the ECG and the prescription of thrombolytic therapy in the coronary care unit., Results: The predictive accuracy of the general practitioner's assessment of the necessity for thrombolytic therapy was 71.5%. The ECG had no impact on the accuracy of this decision and there were problems with the recording and interpretation of the ECG. Clinical decision making was altered in six cases by the ECG: wrongly in four., Conclusion: The diagnostic accuracy among general practitioners would result in some patients who did not have acute myocardial infarction being given thrombolytic therapy. In this study the ECG did not contribute towards diagnostic accuracy. Substantial improvement in both the recording and interpretation of ECGs is needed before thrombolytic agents can be routinely prescribed at home.

Paroxysmal atrial fibrillation is a common, poorly understood and difficult-to-treat arrhythmia. Although it tends to be treated in a similar fashion to chronic atrial fibrillation, its pathophysiology is different, and drugs commonly used for chronic atrial fibrillation may have only limited value in treating paroxysmal atrial fibrillation. A broad range of presenting clinical symptoms may be associated with this arrhythmia, and even in the asymptomatic patient, there may be a risk of serious thromboembolic events. In symptomatic patients, effective control of paroxysms with antiarrhythmic therapy can often be difficult, and the role of anticoagulation remains controversial. This review attempts to clarify these issues, by surveying the range of therapies available.

The incidence, amplitude, mechanism and relationship to prior exposure to streptococcal antigen of blood pressure changes to streptokinase-containing thrombolytic agents were investigated in 125 patients treated with either 1.5 x 10(6) IU streptokinase over 60 min or 30 U anistreplase over 5 min, within 6 h of onset of acute myocardial infarction. Twenty-one of 52 patients with anterior and 34 of 73 with inferior myocardial infarction had a hypotensive response. There were no significant differences in the incidence, duration or amplitude of hypotension between the two treatment groups. The maximum mean fall in systolic blood pressure was 16.9 mmHg (95% confidence limits, CL 12.2 to 24.5 mmHg), and the maximum mean fall in diastolic blood pressure was 13.7 mmHg (CL 10.3 to 17.1 mmHg), starting 4 min after start of therapy and resolving within 34 min. Blood pressure changes were well tolerated. Hypotension was not related to pretreatment streptokinase resistance titre, or anti-SK IgG concentration, to changes in plasma fibrinogen, B-beta 15-42 peptide, D-dimer--as indices of thrombin activation and fibrin (-ogen) breakdown--to plasma viscosity. The blood pressure changes following treatment with streptokinase-containing thrombolytic agents in acute myocardial infarction are frequent but well tolerated. The mechanism of hypotension remains unclear, but is not related to prior exposure to streptococcal antigen.

Adenosine may be of therapeutic and diagnostic value in the emergency management of arrhythmias. It causes transient atrioventricular nodal block and thus ends paroxysmal supraventricular tachycardias that involve the atrioventricular node. Also, it may uncover underlying atrial arrhythmias by slowing the ventricular response. Its duration of action is brief and serious adverse effects have not been reported. A 12 year old patient with atrial flutter is presented, in whom intravenous adenosine was followed by acceleration of the heart rate to a potentially dangerous arrhythmia.

Objective: To examine the induction of antistreptokinase antibodies after giving streptokinase or anistreplase to patients with acute myocardial infarction., Design: Patients were randomly allocated to receive either 1.5 x 10(6) IU, streptokinase or 30U anistreplase in a double blind study. Blood samples were collected immediately before treatment and subsequently at intervals up to 30 months; plasma samples were assayed for streptokinase resistance titre (functional assay) and streptokinase binding by IgG (microradioimmunoassay)., Setting: Cardiology department in a general hospital., Patients: 128 consecutive eligible patients. Samples were collected for up to one year according to a prospective design: a subsection of 47 patients was selected for intensive study over the first 14 days. After one year, all available patients (67) were sampled on one further occasion., Results: Antibody responses to streptokinase and anistreplase were similar. Streptokinase resistance titres exceeded pretreatment concentrations five days after dosing, and values peaked at 14 days. By 12 months after dosing, 92% of resistance titres (n = 84) had returned to within the pretreatment range. Antistreptokinase IgG concentrations also exceeded baseline concentrations within five days and peaked at 14 days. Half of the individual values had returned to within the pretreatment range by 12 months (n = 84) and 89% by 30 months (n = 18)., Conclusion: Although we cannot be sure of the clinical significance, because of the increased likelihood of resistance due to antistreptokinase antibody, streptokinase and anistreplase may not be effective if administered more than five days after an earlier dose of streptokinase or anistreplase, particularly between five days and 12 months, and increased antistreptokinase antibody may increase the risk of allergic-type reactions.

We reviewed our experience with the use of pacing techniques in the acute treatment of spontaneous ventricular tachycardia occurring outside the context of acute myocardial ischaemia. Over a consecutive 18 month period 23 patients (20 male, aged 38-76 yr) admitted to our coronary care unit experienced a total of 75 episodes of haemodynamically tolerated sustained ventricular tachycardia. Pace termination was attempted in 18 patients in a total of 58 episodes of ventricular tachycardia using a standard temporary external pacemaker. Pacing was successful in 32/58 (55%) attempts vs 13/49 (27%) with intravenous antiarrhythmic drug therapy p = 0.003. The superior success rate of pacing was apparent whether or not patients were receiving chronic antiarrhythmic drug therapy. Pace termination should be considered in the treatment of haemodynamically tolerated spontaneous ventricular tachycardias.

Background: Raised lipid peroxide concentrations in coronary venous plasma have been reported after coronary angioplasty in humans. This may reflect increased free radical activity after myocardial ischaemia and reperfusion. If so, it may be possible to correlate lipid peroxide concentrations with the degree of myocardial ischaemia produced during angioplasty., Methods: 15 patients (age range 42-70; 12 men) with stable angina pectoris undergoing angioplasty of a proximal left anterior descending coronary artery stenosis were studied. Plasma lipid peroxide and lactate concentrations were measured in sequential blood samples taken from the great cardiac vein before and immediately after one to five serial 60 second balloon inflations. The maximum ST segment shift during each balloon inflation was also measured., Results: Lipid peroxide concentrations in coronary venous plasma were raised from pre-angioplasty values by more than 2 SDs of the relevant measurement error after 27 out of 46 (59%) balloon inflations. Lactate concentrations were raised after 43 out of 46 (93%) balloon inflations. No significant difference was found between the peak percentage change of either lipid peroxide or lactate concentrations after any of the first three serial inflations. The maximum ST segment shift after each of the first three serial inflations was also similar. Coronary venous lactate concentrations after balloon inflation correlated positively with the maximum ST segment shift, but did not correlate with lipid peroxide concentrations., Conclusions: Raised lipid peroxide concentrations in coronary venous plasma can be detected in humans after balloon angioplasty. There is no positive correlation between lipid peroxide concentrations in coronary venous plasma after angioplasty and the degree of preceding myocardial ischaemia as assessed by either ST segment shift or lactate production. These indices showed that one to three serial 60 second balloon inflations each produce a similar degree of myocardial ischaemia. The origin of the raised lipid peroxide concentrations in coronary venous plasma after angioplasty remains unknown.

Aortic regurgitation associated with relapsing polychondritis usually occurs late in the disease as a result of aortic root dilatation. A case where aortic regurgitation occurred early and was due to cusp rupture with a normal aortic root is reported. The patient required urgent aortic valve replacement within six weeks of developing a murmur despite apparent control of inflammation with immunosuppressive treatment. The possibility of cusp rupture with sudden haemodynamic deterioration should be considered in patients with relapsing polychondritis who develop aortic regurgitation.

Objective: To examine the efficacy, safety, and the pharmacokinetic profile of a bolus dose administration regimen of alteplase in the treatment of acute myocardial infarction., Design: An open pilot study., Setting: District general hospital., Patients: 33 suitable consecutive patients presenting within six hours of the onset of symptoms who satisfied the electrocardiographic criteria for acute myocardial infarction., Interventions: Two intravenous boluses of 35 mg alteplase, 30 minutes apart., Main Outcome Measures: Angiographic coronary patency at 90 minutes and 24 hours. Plasma alteplase concentration-time profile and pharmacokinetic analysis., Results: Coronary patency at 90 minutes: 26 of 30 arteries (87%, 95% confidence interval (CI) 74-99%). Coronary patency at 24 hours: 24 of 29 arteries (83%, CI 69-97%). Mean (SD) plasma tissue plasminogen activator (t-PA) concentration reached 4434.8 (2117.8) and 4233.3 (2217.5) ng/ml within 10 minutes of each bolus and fell to 425.8 (288.3) ng/ml between boluses. The estimated peak concentrations at two minutes after boluses were 12,389 (8580) ng/ml and 10,811 (6802) ng/ml. The derived pharmacokinetic variables were volume of distribution 3.11 (1.89) 1, clearance 21.3 (9.3) 1/h, half life 5.9 (1.7) minutes., Conclusions: This simple administration regimen achieved brief, high concentrations of plasma t-PA that were well tolerated. The regimen was associated with a high coronary patency rate at 90 minutes that was well maintained at 24 hours.

Objective: To compare the effects of dual chamber pacing (DDD) and ventricular rate adaptive pacing (activity sensing) (VVIR) in patients with complete heart block., Design: Double blind crossover comparison with one month in each pacing mode., Patients: 10 consecutive patients aged 23-74 presenting with complete anterograde atrioventricular block at rest and on exercise and with an intact atrial rate response received Synergyst I (Medtronic) pacemakers., Main Outcome Measures: Symptom scores, maximal exercise performance on a treadmill, and the plasma concentrations of atrial natriuretic peptide, adrenaline, and noradrenaline., Results: No significant differences were identified between pacing modes in symptom scores for dyspnoea, fatigue, and mood disturbance; exercise time; and maximal oxygen consumption. One patient with intact ventriculoatrial conduction developed pacemaker syndrome during VVIR pacing. Resting plasma concentrations of atrial natriuretic peptide were raised in complete heart block and were restored to normal by DDD pacing but not by VVIR pacing. Resting plasma catecholamine concentrations were normal in complete heart block and in both pacing modes. During exercise the increase in the concentrations of all three hormones was similar in both pacing modes., Conclusions: In patients with complete anterograde and retrograde atrioventricular block, symptoms and maximal exercise performance were no better during DDD than during VVIR pacing.

1. The pharmacokinetics of streptokinase (SK) and anistreplase in conventional dosage regimens of 1.5 x 10(6) i.u. of SK infused over 60 min and 30 units of anistreplase over 5 min were studied in 24 consecutive patients presenting with acute myocardial infarction, using a functional bioassay to assess concentrations. 2. The two agents were found to have similar volumes of distribution (5.68 and 5.90 l), but SK was cleared significantly more rapidly than anistreplase, resulting in a shorter terminal phase half-life (0.61 vs 1.16 h) and a shorter mean residence time (0.76 vs 1.55 h).

In a prospective blind study, continuous and pulsed wave Doppler echocardiography were used to predict the severity of angiographically assessed aortic regurgitation in 36 patients. High quality continuous wave spectral recordings of the regurgitant jet were obtained in 32 patients but four patients with mild aortic regurgitation had dropout of high velocity signals precluding accurate assessment. The deceleration slope of the peak to end-diastolic velocity measured by continuous wave Doppler, and pulsed wave Doppler mapping of the regurgitant jet in the left ventricle were compared with angiographic severity. The deceleration slope was significantly steeper in patients with severe rather than mild or moderate aortic regurgitation (3.65 +/- 1.04 vs. 1.89 +/- 0.42 vs. 1.52 +/- 0.59 m sec-2). A decay slope of greater than 3 m sec-2 was observed only in patients with 3+ or 4+ aortic regurgitation and a decay slope less than 1.2 m sec-2 was seen only in mild 1+ aortic regurgitation but there was considerable overlap between groups, making it difficult in individual cases to assess severity on the basis of the continuous wave deceleration slope. The pulsed wave Doppler technique was more time consuming, added little to the continuous wave Doppler assessment and underestimated severe regurgitation in almost 50% of cases. Hence, there are significant problems using either Doppler technique in quantitatively assessing aortic regurgitation.

The serum concentration of C-reactive protein was prospectively assessed in 37 patients with various degrees of heart failure. The serum concentration of C-reactive protein was higher than normal in 26 (70%) patients. The concentration was directly related to the severity of heart failure and the stage of decompensation. Hepatic cell damage is the most likely stimulus to cytokine production and hence release of C-reactive protein in heart failure. Heart failure is an additional cause of raised serum concentration of C-reactive protein but the pathological importance of this feature is not yet known.

128 patients with acute myocardial infarction of duration 6 h or less were randomised in double-blind fashion to receive 30 U anistreplase over 5 min or 1.5 MU streptokinase over 1 h, both intravenously. Angiographic patency was assessed 90 min and 24 h from the start of therapy. 55% of patients who received anistreplase and 53% of patients who received streptokinase had patent infarct-related arteries (TIMI grade 2-3) at 90 min (95% CI 42-68% and 40-66%, respectively). At 24 h 81% and 87.5% of arteries were patent respectively (95% CI, 71-91% and 83.5-91.5%). Time to therapy had no significant effect on patency rates. There was one early reocclusion within 24 h in each treatment group and clinical evidence of reocclusion was recorded between 24 h and hospital discharge in a further 5 patients (streptokinase 3, anistreplase 2). With these regimens, therefore, anistreplase and streptokinase gave the same patency rates.

A comparison of verapamil with adenosine for the immediate treatment of supraventricular tachycardia was made from a retrospective review of 164 spontaneous episodes of paroxysmal tachycardia in 43 patients. Verapamil administered to 33 patients restored sinus rhythm in 91 of 112 episodes (81 per cent). Hypotension occurred in 9 per cent of episodes. Adenosine terminated 94 per cent of episodes of supraventricular tachycardia in 25 patients. The arrhythmia recurred shortly after adenosine restored sinus rhythm in 20 episodes. Transient side effects were common. Fifteen patients were treated with both agents. Adenosine was successful in all, but verapamil failed to restore sinus rhythm at least once in seven of the 15 patients. Early recurrence of tachycardia occurred in five of these after adenosine, but in only one after verapamil. Verapamil and adenosine are both effective in the treatment of supraventricular tachycardia; adenosine has the higher success rate and is safer, but transient symptoms are common and arrhythmias may recur.

The effects of intravenous adenosine and adenosine triphosphate (ATP) were studied in a double-blind randomized study during 68 episodes of supraventricular tachycardia in 39 patients. Adenosine restored sinus rhythm in 20 patients (25 of 27 episodes) and produced atrioventricular block to reveal atrial arrhythmias in nine. ATP restored sinus rhythm in 17 patients (22 of 25 episodes) and revealed atrial tachyarrhythmias in six. In patients receiving both compounds, the effective dosage of adenosine was 3.8 mg and of ATP it was 6.6 mg (p less than 0.05), suggesting molar equipotency. Transient side effects were common, occurring in 81% of episodes with adenosine and in 94% with ATP. Symptom scores (0 to 10) were not significantly different (median score for adenosine was 5, for ATP it was 6). Adenosine and ATP were equally effective for the diagnosis and treatment of supraventricular tachycardias and the incidence and severity of side effects were similar. Adenosine has the advantage of being more stable.

To determine whether failure of procainamide to prevent initiation of ventricular tachyarrhythmias during electrophysiologic testing predicted failure of other antiarrhythmic regimens, 81 consecutive patients with coronary artery disease whose ventricular tachyarrhythmias remained inducible during procainamide administration were studied. Overall, 26 (12%) of 216 subsequent drug studies were successful and at least one effective drug regimen was identified in 22 (27%) of the 81 patients. Drug success was significantly related to the arrhythmia induced at baseline study; 7% of drug studies were successful in patients with sustained ventricular tachycardia, 24% in patients with ventricular fibrillation, and 29% in patients with nonsustained ventricular tachycardia. An effective drug regimen was found in 11 (19%) of 59 patients with sustained ventricular tachycardia, 4 (50%) of 8 patients with ventricular fibrillation and 7 (50%) of 14 patients with nonsustained ventricular tachycardia. In patients with sustained ventricular tachycardia, failure of procainamide to suppress the arrhythmia correlated with failure of other agents used singly but not in combination. This study supports the view that when procainamide fails to prevent initiation of the arrhythmia in patients with inducible sustained ventricular tachycardia it is unlikely that other individual standard agents will be effective. However, combination regimens may suppress the arrhythmia and should be evaluated. In patients with nonsustained ventricular tachycardia, all agents should be evaluated because failure to respond to procainamide does not predict subsequent responses to other agents either alone or in combination.

The effects of different types of adrenoreceptor blocking agents on portal venous pressure were studied in patients with cirrhosis and portal hypertension. Oral atenolol (selective beta 1 blocker), propranolol (non-selective beta 1 and beta 2 blocker), and prazosin (alpha blocker) were compared in three groups of eight patients. Haemodynamic measurements were made before and after two or three and eight weeks of therapy. The dose of beta blockers was sufficient to reduce the exercise heart rate by more than 25%. Propranolol and prazosin produced a sustained reduction in the mean portohepatic venous pressure gradient of the order of 25% and 18% respectively. The cardiac index was significantly reduced by propranolol but not altered by prazosin. Atenolol produced an early reduction in portohepatic venous pressure which, although not sustained, showed a good correlation with reduction in cardiac index. No such relationship was found with propranolol. All three drugs were well tolerated by these patients with advanced cirrhosis. Therefore propranolol and prazosin have proved to be effective agents for the reduction of portal venous pressure.

The antihypertensive effect and a non-invasive cardiovascular assessment of indapamide in patients with idiopathic hypertension have been investigated in an uncontrolled study. Indapamide was found to be an effective antihypertensive agent in a dose of 2.5 mg per day with a mean fall in blood pressure of 25/18 mmHg. Apart from the development of impotence in one patient, no side effects were encountered. Its effect on heart rate and cardiac output suggest that vasodilatation may contribute to its mode of action. Exercise performance is well maintained and cardiac performance appears to improve when blood pressure is lowered with this drug.

The relation between plasma norepinephrine levels and the occurrence of ventricular tachycardia during exercise testing was prospectively evaluated in 17 patients. Ten patients had reproducible ventricular tachycardia exclusively during exercise or recovery, or both; 7 patients had ventricular tachycardia only during ambulatory electrocardiographic monitoring. The two groups did not differ in age, exercise duration, left ventricular ejection fraction at rest, heart rate throughout the exercise protocol, rest QTc interval, change in QTc interval during exercise, the presence of coronary artery disease or exercise-related myocardial ischemia. Furthermore, there was no difference between groups in plasma norepinephrine levels at rest, peak exercise or in the recovery period. Myocardial ischemia was detectable by thallium perfusion scan in only 2 of the 10 patients with exercise-induced ventricular tachycardia. The 10 patients with exercise-induced ventricular tachycardia underwent repeat exercise testing immediately after maximal intravenous beta-adrenergic blockade with propranolol. Although they had no change in exercise duration, ventricular tachycardia did not occur in 9 of these 10 patients. Plasma norepinephrine levels were significantly decreased compared with levels before beta-adrenergic blockade (p less than 0.0002). Thus, plasma norepinephrine levels do not distinguish patients with reproducible exercise-induced ventricular tachycardia from otherwise comparable patients. Propranolol is highly effective in abolishing this arrhythmia and this effect is associated with decreased norepinephrine levels.

Symptoms range from mild palpitations to overt cardiac failure and cardiogenic shock, depending on the ventricular rate and the patient's underlying cardiac status. Drug therapy is the mainstay treatment. In atrial fibrillation, digoxin is used to control the ventricular response and therefore improve cardiac function. Verapamil may also be used for this purpose.

The efficacy of combination therapy using a type IA agent (quinidine or procainamide) and a type IB agent (mexiletine) in suppressing inducible sustained ventricular tachyarrhythmias was studied in 23 patients undergoing serial drug testing with programmed stimulation. All patients had coronary artery disease (CAD) with previous myocardial infarction and abnormal left ventricular function (mean ejection fraction 35%). Fifty-five percent of the patients presented with syncope or cardiac arrest. In 19 patients therapy had failed during empiric trials of 1 to 3 antiarrhythmic agents. All 23 patients had inducible sustained ventricular tachyarrhythmias (18 had uniform morphology sustained ventricular tachycardia (VT) and 5 had ventricular fibrillation [VF]) during control electrophysiologic study, and therapy had failed with a type IA agent and mexiletine alone. The combination therapy of mexiletine and the type IA agent prevented induction of any ventricular tachyarrhythmias in 8 of 23 patients. In 15 patients, the combination significantly prolonged the tachycardia cycle length and reduced the symptoms associated with the induced arrhythmia. Patients more likely to respond to the combination had shorter cycle lengths and polymorphic configuration of the control-induced arrhythmia. The increased efficacy of the combination therapy could not be attributed to higher plasma drug levels for the combination, as there was no significant difference in plasma levels for each drug when given alone or in combination. Thus, the increased efficacy most likely reflects a synergistic electropharmacologic effect of the 2 agents.(ABSTRACT TRUNCATED AT 250 WORDS)

The impaired cardiac performance in patients with congestive cardiac failure may be improved by the introduction of inotropic therapy. Dopamine and dobutamine are both potent cardiac stimulants although their haemodynamic profile is different. Dobutamine would appear to be the more appropriate choice in cardiac failure because of the additional benefit of preload reduction although in the context of severe hypotension dopamine would be preferred. The need for intravenous administration, however, limits their clinical application. In acute studies, the oral agents prenalterol and pirbuterol, are effective in improving myocardial function; pirbuterol mainly due to peripheral vasodilatation and afterload reduction. There are few chronic studies but confirmation of sustained haemodynamic improvement is lacking. This could be due, either to the inexorable deterioration in cardiac function or to a reduction in the beta receptor population available for catecholamine stimulation.

BRL 26921 is the p- anisoyl derivative of the primary streptokinase-human plasminogen complex in which the acyl group is specifically located at the catalytic centre of the enzyme. Doses of BRL 26921 ranging from 5 mg to 25 mg were given intravenously or into a coronary artery to 12 patients with acute myocardial infarction. The complex was well tolerated and produced no serious bleeding. Coronary artery reperfusion was demonstrated angiographically in three patients. In most patients, fibrinogen, plasminogen, alpha 2 antiplasmin and alpha 2 macroglobulin levels fell and the level of fibrinogen degradation products increased acutely post treatment indicating systemic fibrinolytic activation. The degree of this activation was variable but was profound in some. It appeared to be dose related and modified by the presence of streptokinase antibodies. BRL 26921 appears less "selectively" thrombolytic in patients than had been expected from animal models.