Risk of coronary stenosis after adjuvant radiotherapy for breast cancer.

PURPOSE: Adjuvant radiotherapy (RT) for breast cancer is associated with an increased risk of ischemic heart disease. We examined the risk of coronary artery stenosis in a large cohort of women with breast cancer receiving adjuvant RT. METHODS: A cohort of women diagnosed with breast cancer between 1992 and 2012 in three Swedish health care regions (n = 57,066) were linked to the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) to identify women receiving RT who subsequently underwent a percutaneous coronary intervention (PCI) due to coronary stenosis. Cox regression analyses were performed to examine risk of a coronary intervention and competing risk analyses were performed to calculate cumulative incidence. RESULTS: A total of 649 women with left-sided breast cancer and 494 women with right-sided breast cancer underwent a PCI. Women who received left-sided RT had a significantly higher risk of a PCI in the left anterior descending artery (LAD) compared to women who received right-sided RT, hazard ratio (HR) 1.44 (95% confidence interval [CI] 1.21-1.77, p < 0.001). For the proximal, mid, and distal LAD, the HRs were 1.60 (95% CI 1.22-2.10), 1.38 (95% CI 1.07-1.78), and 2.43 (95% CI 1.33-4.41), respectively. The cumulative incidence of coronary events at 25 years from breast cancer diagnosis were 7.0% in women receiving left-sided RT and 4.4% in women receiving right-sided RT. CONCLUSION: Implementing and further developing techniques that lower cardiac doses is important in order to reduce the risk of long-term side effects of adjuvant RT for breast cancer.

Mortality and extent of coronary artery disease in 2776 patients with type 1 diabetes undergoing coronary angiography: A nationwide study.

Background In a modern perspective there is limited information on mortality by affected coronary vessels assessed by coronary angiography in patients with type 1 diabetes. The aim of the present study was to characterise distribution of coronary artery disease and impact on long-term mortality in patients with type 1 diabetes undergoing coronary angiography. Design The design of this research was a nationwide population-based cohort study. Methods Individuals ( n = 2776) with type 1 diabetes undergoing coronary angiography 2001-2013 included in the Swedish National Diabetes Registry and Swedish Coronary Angiography and Angioplasty Registry were followed for mortality until 31 December 2013 (mean 7.1 years). In 79% the indication was stable or acute coronary artery disease. Coronary artery disease was categorised into normal (21%), one- (23%), two- (18%), three- (29%) and left main-vessel disease (8%). Results Mean age was 57 years and 58% were male. Mean diabetes duration was 35 years, glycated haemoglobin was 67 mmol/mol and 44% had normal or one-vessel disease. In multivariate Cox proportional analyses hazard ratio for mortality compared with normal findings was 1.09 (95% confidence interval 0.80-1.48) for one, 1.43 (1.05-1.94) for two, 1.47 (1.10-1.96) for three and 1.90 (1.35-2.68) for left main-vessel disease. Renal failure 2.29 (1.77-2.96) and previous heart failure 1.76 (1.46-2.13) were highly associated with mortality. Standard mortality ratio the first year was 5.55 (4.65-6.56) and decreased to 2.80 (2.18-3.54) after five years. Conclusions In patients with type 1 diabetes referred for coronary angiography mortality is influenced by numbers of affected coronary vessels. The overall mortality rate was higher compared with the general population. These results support early intensive prevention of coronary artery disease in this population.

Comparison of interventional cardiology in two European countries: a nationwide Internet based registry study.

BACKGROUND: The practice of interventional cardiology differs between countries and regions. In this study we report the results of the first nation-wide long-term comparison of interventional cardiology in two countries using a common web-based registry. METHODS: The Swedish Coronary Angiography and Angioplasty Registry (SCAAR) was used to prospectively and continuously collect background-, quality-, and outcome parameters for all coronary angiographies (CA) and percutaneous coronary interventions (PCI) performed in Iceland and Sweden during one year. RESULTS: The rate of CA per million inhabitants was higher in Iceland than in Sweden. A higher proportion of patients had CA for stable angina in Iceland than in Sweden, while the opposite was true for ST elevation myocardial infarction. Left main stem stenosis was more commonly found in Iceland than in Sweden. The PCI rate was similar in the two countries as was the general success rate of PCI, achievement of complete revascularisation and the overall stent use. Drug eluting stents were more commonly used in Iceland (23% vs. 19%). The use of fractional flow reserve (0.2% vs. 10%) and the radial approach (0.6% vs. 33%) was more frequent in Sweden than in Iceland. Serious complications and death were very rare in both countries. CONCLUSION: By prospectively comparing interventional cardiology in two countries, using a common web based registry online, we have discovered important differences in technique and indications. A discovery such as this can lead to a change in clinical practice and inspire prospective multinational randomised registry trials in unselected, real world populations.

Long-term mortality in patients with type 2 diabetes undergoing coronary angiography: the impact of glucose-lowering treatment.

AIMS/HYPOTHESIS: The aim of this study was to analyse whether the increased mortality rates observed in insulin-treated patients with type 2 diabetes and coronary artery disease are explained by comorbidities and complications. METHODS: A retrospective analysis of data from two Swedish registries of type 2 diabetic patients (n = 12,515) undergoing coronary angiography between the years 2001 and 2009 was conducted. The association between glucose-lowering treatment and long-term mortality was studied after extensive adjustment for cardiovascular- and diabetes-related confounders. Patients were classified into four groups, according to glucose-lowering treatment: diet alone; oral therapy alone; insulin in combination with oral therapy; and insulin alone. RESULTS: After a mean follow-up time of 4.14 years, absolute mortality rates for patients treated with diet alone, oral therapy alone, insulin in combination with oral therapy and insulin alone were 19.2%, 17.4%, 22.9% and 28.1%, respectively. Compared with diet alone, insulin in combination with oral therapy (HR 1.27; 95% CI 1.12, 1.43) and insulin alone (HR 1.62; 95% CI 1.44, 1.83) were associated with higher mortality rates. After adjustment for baseline differences, insulin in combination with oral glucose-lowering treatment (HR 1.22; 95% CI 1.06, 1.40; p < 0.005) and treatment with insulin only (HR 1.17; 95% CI 1.02, 1.35; p < 0.01) remained independent predictors for long-term mortality. CONCLUSIONS/INTERPRETATION: Type 2 diabetes patients treated with insulin and undergoing coronary angiography have a higher long-term mortality risk after adjustment for measured confounders. Further research is needed to evaluate the optimal glucose-lowering treatment for these high-risk patients.

Is late stent thrombosis in drug-eluting stents a real clinical issue? A single-center experience and review of the literature.

BACKGROUND: Randomized studies have not found an increased rate of late stent thrombosis (LAST) in drug-eluting stents (DES) compared with bare metal stents (BMS) but those studies were statistically not powered to show such a difference. At the same time there is an increasing number of reports of LAST in DES patients in the current literature. PATIENTS AND METHODS: We tried to describe the incidence of LAST in an unselected DES and BMS patient population. All patients who underwent stenting in our hospital between October 2003 and March 2006 were included in the study (n=1377). A total of 424 (30.1%) patients were treated with only BMS stents, 520 (37.8%) with paclitaxel-eluting stents (PES), 384 (27.9%) with sirolimus-eluting stents (SES) and 49 (3.6%) with BMS and DES. Long-term follow-up of all patients was used to determine the incidence of LAST as defined by angiographically proven stent thrombosis associated with acute symptoms more than 30 days after stent implantation. Followup was between 1 month and 2 years 7 months (mean 12 months). Patients treated with DES were younger (66+/-11 years) than BMS patients (72+/-10 years; p<0.001) and more often had diabetes (24.2% vs 17.4%; p < 0.001). A previous PCI had been performed in 27.1% of DES patients vs 13.9% of BMS patients (p < 0.001). RESULTS: There were 9 cases of LAST: 2 with SES (at 6 and 11 months after implantation), 6 with PES (at 6, 9 (2x), 10, 16 and 26 months), and one with BMS (at 22 months). All patients with LAST presented with STEMI and without an angina history that suggested restenosis. Two cases were related to complete cessation of antiplatelet therapy, one because of patient non-compliance (SES), one after aspirin was stopped for orthopedic surgery (BMS). Two cases occurred within 1 month of cessation of clopidogrel therapy and while these patients were on aspirin therapy. Five cases occurred on aspirin monotherapy 2, 3, 4, 10 and 20 months, respectively after planned cessation of clopidogrel. None of the cases occurred under dual antiplatelet therapy. All patients underwent primary PCI; none died. CONCLUSION: Angiographically proven LAST occurred in our unselected patient population with an incidence of 0.84% in patients treated with DES and 0.21% in BMS patients within a mean follow-up of 12 months (p = 0.36). LAST may indeed occur in clinically stable patients while on aspirin monotherapy. Since LAST led in all patients to STEMI it seems to be a serious clinical issue that prompts further investigation and discussion of length of dual platelet therapy.

Renal failure in 57 925 patients undergoing coronary procedures using iso-osmolar or low-osmolar contrast media.

We compared the Swedish Coronary Angiography and Angioplasty Registry with the Swedish 'Hospital Discharge Register' to assess contrast media (CM)-induced renal failure. Hospitals used only one type CM. From 2000 to 2003, iodixanol (iso-osmolar) was used in 45 485 patients, ioxaglate (low osmolar) in 12 440 subjects. To include the earlier used CM iohexol (low osmolar), analysis extended back to 1990 (86 334 patients). Incidence of clinically significant renal failure was greatest for patients receiving the iso-osmolar CM iodixanol (1.7%). Ioxaglate-treated patients had a significantly lower renal failure incidence (0.8%, P<0.001). The odds ratio for iodixanol-treated patients was significantly higher than for ioxaglate (1 vs 0.48, P<0.001). In subsets of either diabetic patients or patients with previous renal failure, odds ratios for renal failure remained greater in the iodixanol groups (P<0.01). Hospitals switching CM to iodixanol experienced a doubling in clinically significant renal failure after cardiac procedures. Dialysis was required in 0.2% of patients receiving iodixanol, which was significantly higher (P<0.01) than for ioxaglate-treated patients (0.1%). Iohexol-treated patients had a similar low risk for developing clinically significant renal failure (0.9%) as ioxaglate. In conclusion, risk of developing renal failure and required dialysis after coronary procedures is higher when patients received iodixanol than ioxaglate or iohexol.

Effects on mortality of abciximab in ST-elevation myocardial infarction treated with percutaneous coronary intervention including stent implantation.

OBJECTIVES: To investigate the effects of abciximab on mortality in ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) including stent implantation. DESIGN: Meta-analysis of three selected randomized studies and analysis of data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). SUBJECTS: Pooled data from randomized studies containing in total 1,736 patients undergoing PCI with stent implantation because of STEMI with duration between symptom and treatment <12 h, and 7,436 patients from SCAAR treated with PCI because of STEMI (52% treated with abciximab) in Sweden 2000-2004. RESULTS: Analyses of pooled data showed that abciximab was associated with a decreased risk of reinfarction [odds ratio (OR) 0.38] and urgent target vessel revascularization (OR 0.38) at 30 days. No effect was seen on mortality at 30 days or 6 months. Multivariate analysis of data from SCAAR showed that abciximab reduced the risk of death during 14 months of follow-up (hazard ratio 0.82). CONCLUSIONS: The results are encouraging and support the ACC/AHA and ESC recommendation to use abciximab in treatment of STEMI with PCI including stent implantation. Considering that the pooled results from previous trials showed no effect of abciximab on mortality and the registry part of the present study was observational, the results encourage carrying out new randomized studies of abciximab in STEMI treated with PCI, including stent implantation, with sufficient size and length of follow-up.

Clinical and angiographic follow-up after coronary drug-eluting and bare metal stent implantation. Do drug-eluting stents hold the promise?

OBJECTIVES: To investigate the influence of drug-eluting stent (DES) implantation on clinical and angiographic restenosis. DESIGN: Registry study of data from the Swedish Coronary Angiography and Angioplasty Registry with a coronary angiographic substudy. SETTING: Multi-centre study. SUBJECTS: During October 2002 to May 2004 a total of 23 590 percutaneous coronary intervention (PCI) procedures were performed at 25 hospitals. After selection, to achieve comparable groups, a total of 5068 patients of whom 4111 had a bare metal stent (BMS) implanted and 957 had a DES implanted, remained. End-point in the registry follow-up was >50% diameter restenosis at clinically driven reangiography within 12 months after index PCI. The primary end-point in the angiographic substudy was late loss in patients' DES at 6-month angiographic follow-up. RESULTS: The rate of clinically driven restenosis, within 12 months, in patients receiving DES was less (3.9%) compared with those who received BMS (7.0%). In multivariate analysis the risk of clinical restenosis was one-third for DES compared with BMS (HR 0.36, 95% CI 0.25-0.52). In the angiographic substudy late loss was 0.07+/-0.53 mm (range -0.88 to 1.62). The amount of late loss was related to the presence of diabetes mellitus or not (0.19+/-0.45 mm vs. -0.12+/-0.58 mm), and lack of postdilatation of the stent or not (0.23+/-0.51 mm vs. -0.09+/-0.50 mm). CONCLUSIONS: The use of DES in the Swedish 'real world' is effective in reducing the clinically driven restenosis rate, when compared with patients with BMS treatment. In the angiographic follow-up the average late loss was as low as observed in recent randomized multi-centre trials.

FRISC score for selection of patients for an early invasive treatment strategy in unstable coronary artery disease.

OBJECTIVE: To develop a scoring system for risk stratification and evaluation of the effect of an early invasive strategy for treatment of unstable coronary artery disease (CAD). DESIGN: Retrospective analysis of a randomised study (FRISC II; fast revascularisation in instability in coronary disease). SETTING: 58 Scandinavian hospitals. PATIENTS: 2457 patients with unstable CAD from the FRISC II study. MAIN OUTCOME MEASURES: One year rates of mortality and death/myocardial infarction (MI). METHODS: Patients were randomly assigned to an early invasive or a non-invasive strategy. From the non-invasive cohort independent variables of death or death/MI were identified. RESULTS: Seven factors, age > 70 years, male sex, diabetes, previous MI, ST depression, and increased concentrations of troponins and markers of inflammation (interleukin 6 or C reactive protein), were associated with an independent increased risk for death or death/MI. In patients with > or = 5 of these factors the invasive strategy reduced mortality from 15.4% (20 of 130) to 5.2% (7 of 134) (risk ratio (RR) 0.34, 95% confidence interval (CI) 0.15 to 0.78, p = 0.006). Death/MI was also reduced in patients with 3-4 factors from 15.7% (80 of 511) to 10.8% (58 of 538) (RR 0.69, 95% CI 0.50 to 0.94, p = 0.02). Neither death nor death/MI was reduced in patients with 0-2 risk factors. CONCLUSION: In unstable CAD, this scoring system based on factors independently associated with an adverse outcome can be used shortly after admission to the hospital for risk stratification and for selection of patients to an early invasive treatment strategy.

Benefits of extended treatment with dalteparin in patients with unstable coronary artery disease eligible for revascularization.

AIMS: The FRISC II trial demonstrated that, for patients with unstable coronary artery disease, an early invasive strategy following acute treatment with dalteparin and aspirin, was superior to a more conservative approach. We evaluated whether it is beneficial to extend treatment with dalteparin to patients eligible for revascularization but for whom these procedures are performed after the initial hospital stay. METHODS AND RESULTS: As a subanalysis of FRISC II, the efficacy and clinical safety of extended dalteparin treatment (5000 or 7500 IU.12h(-1) to day 90) compared with placebo was assessed in 1601 patients randomized to a non-invasive group who underwent revascularization only when necessary because of recurring symptoms, (re)infarction, or severe ischaemia. By day 90, 440 patients had undergone revascularization: 267 of these procedures occurred during the double-blind period. All patients initially received acute treatment (5-7 days from day 1) with dalteparin (120 IU/kg(-1) 12h(-1)). The incidence of death and/or myocardial infarction was monitored until revascularization or day 45 and until revascularization or day 90. There was a significant difference in the estimated probability of death and/or myocardial infarction until revascularization or day 90 in favour of dalteparin (log-rank test, P=0.0415) and there was a significant reduction in death and/or myocardial infarction in favour of extended dalteparin treatment at day 45, with a 57% relative risk reduction (P=0.0004). At day 90 the relative risk reduction was 29%. The safety profile of extended dalteparin treatment was similar to that of acute usage. CONCLUSION: Extended dalteparin treatment for up to 45 days is effective and safe as a bridging therapy for patients with unstable coronary artery disease awaiting revascularization.

Clinical performance of three cardiac troponin assays in patients with unstable coronary artery disease (a FRISC II substudy).

The assay of cardiac-specific troponins (cTroponins) is a sensitive and specific means to diagnose myocardial injury. Several assays for the measurement of cardiac-specific troponin I (cTnI), but only 1 for the assay of cardiac specific troponin T (cTnT), are commercially available. The aim of this study was to compare 3 of these assays (i.e., Access AccuTnI [cTnI], AxSym [cTnI], and Elecsys 3(rd) generation [cTnI]) and their clinical performances in a group of patients (n = 1,763) with unstable coronary artery disease (Fragmin and fast Revascularisation during InStability in Coronary artery disease [FRISC II] trial). Clinical events after 1-year follow-up, such as death and death and/or acute myocardial infarction, were recorded and the effects of invasive or noninvasive treatment evaluated in relation to cTroponin levels. Overall the 2 cTnI methods showed good correlation (r(s) = 0.96), whereas correlations to the cTnT assay were somewhat lower (r(s) = 0.93). Patients with nonelevated levels, as measured with any of the 3 biomarkers, had a significantly better prognosis than patients with elevated levels (p <0.001). A cohort of 10% to 12.4% of patients with a poor prognosis was identified only by the Access AccuTnI assay. Invasive treatment reduced clinical events only in the group of patients with elevated cTroponin levels. We conclude that stratification of patients with unstable coronary artery disease by means of cTroponin measurements is important in clinical management. It is also apparent that assays with superior sensitivity, such as the Access AccuTnI, identify more patients with poor prognosis who are candidates for early invasive procedures.

ST depression in ECG at entry indicates severe coronary lesions and large benefits of an early invasive treatment strategy in unstable coronary artery disease; the FRISC II ECG substudy. The Fast Revascularisation during InStability in Coronary artery disease.

BACKGROUND: In unstable coronary artery disease, ST-segment depression indicates a poor prognosis. We evaluated whether the effect of early revascularization and the extent of coronary lesions were related to ST-segment and T wave changes on admission. METHODS AND RESULTS: 2457 patients with unstable coronary artery disease were randomized to an early invasive strategy with coronary angiography/revascularization within 7 days or to a non-invasive strategy with coronary procedures only when symptoms or severe ischaemia recurred. ST depression was present in 1114 (45.5%) patients. In the invasive group, 45% of the patients with ST depression had three-vessel disease or left main stenosis compared with 22% if no ST-segment depression was present, PP=0.004 while mortality was changed from 5.8 to 3.3%, P=0.050. In patients without ST-segment depression the corresponding rates concerning death/myocardial infarction were 10.4 and 8.9, and for mortality 2.0 and 1.2% (non-significant). CONCLUSIONS: In unstable coronary artery disease, ST-segment depression is associated with a 100% increase in the occurrence of three-vessel/left main disease and to an increased risk of subsequent cardiac events. In these patients an early invasive strategy substantially decreases death/myocardial infarction.

Mechanisms behind the prognostic value of troponin T in unstable coronary artery disease: a FRISC II substudy.

OBJECTIVES: This study was designed to elucidate possible mechanisms for the prognostic value of troponin T (tnT). BACKGROUND: The reasons for the adverse prognosis associated with elevation of troponins in unstable coronary artery disease are poorly understood. METHODS: Patients enrolled in the Fast Revascularization during InStability in CAD (FRISC-II) trial were included. Clinical characteristics, findings at echocardiography and coronary angiography, and prognosis were evaluated in relation to different tnT levels. RESULTS: Absence of significant coronary stenosis was more frequent and three-vessel disease or left main stem stenosis was less frequent in patients without, compared with, detectable tnT. The occurrence of visible thrombus increased with rising levels of tnT. In the group with the highest levels of tnT, occlusion of the left circumflex artery was more common than in the three other tnT groups, as was a left ventricular ejection fraction below 0.45. The one-year risk of death in the noninvasive arm of the study increased by increasing levels of tnT (1.6% to 4.6%), whereas the risk of myocardial infarction showed an inverted U-shaped curve and was lower in the lowest (5.5%) and highest (8.4%) tnT groups than in the two intermediate groups (17.5% and 16.2%). CONCLUSIONS: Any detectable elevation of tnT raises the probability of significant coronary stenosis and thrombus formation and is associated with an increased risk of reinfarction and death. However, at a more pronounced elevation of troponin, a higher proportion of patients has a persistent occlusion of the culprit vessel and reduced left ventricular function, associated with a high mortality but a modest risk of reinfarction.

Is early invasive treatment of unstable coronary artery disease equally effective for both women and men? FRISC II Study Group Investigators.

BACKGROUND: The Fragmin and fast Revascularization during InStability in Coronary artery disease (FRISC II) trial compared the effectiveness of an early invasive versus a noninvasive strategy in terms of the incidence of death and myocardial infarction (MI) in patients with unstable coronary artery disease (CAD). OBJECTIVES: In this subanalysis, we sought to evaluate gender differences in the effect of these different strategies. METHODS: The patients (749 women and 1,708 men) were randomized to early invasive or noninvasive strategies. Coronary angiography was performed within the first 7 days in 96% and 10% of the invasive and noninvasive groups, respectively, and revascularization was performed within the first 10 days in 71% and 9% of the invasive and noninvasive groups, respectively. RESULTS: Women presenting with unstable CAD were older, but fewer had previous infarctions, left ventricular dysfunction and elevated troponin T levels. Women had fewer angiographic changes. There was no difference in MI or death at 12 months among women in the invasive and noninvasive groups (12.4% vs. 10.5%, respectively), in contrast to the favorable effect in the invasively treated group of men (9.6% vs. 15.8%, p < 0.001). In an interaction analysis, there was a different effect of the early invasive strategy for the two genders (p = 0.008). CONCLUSIONS: Women with symptoms and/or signs of unstable CAD are older, but still have less severe CAD and a better prognosis compared with men. In contrast to its beneficial effect in men, an early invasive strategy did not reduce the risk of future events among women. Further research is warranted to identify the most appropriate treatment strategy in women with unstable CAD.

Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial. FRISC II Investigators. Fast Revascularisation during Instability in Coronary artery disease.

BACKGROUND: The Fragmin and Fast Revascularisation during Instability in Coronary artery disease II trial (FRISC II) compared an early invasive with an early non-invasive strategy in unstable coronary-artery disease. We report outcome at 1 year. METHODS: 2457 patients were randomly assigned invasive or non-invasive treatment and 3 months of dalteparin or placebo. Complete information at 1 year was available for 1222 in the invasive group and 1234 in the non-invasive group. Analyses were by intention to treat. FINDINGS: Revascularisation was done within the first 10 days in 71% of the invasive group and 9% of the non-invasive group and within the first year in 78% and 43%. During the first year, 27 (2.2%) patients in the invasive group and 48 (3.9%) in the non-invasive group died (risk ratio 0.57 [95% CI 0.36-0.90], p=0.016). 105 (8.6%) versus 143 (11.6%) had myocardial infarction (0.74 [0.59-0.94], p=0.015). The composite of death or myocardial infarction occurred in 127 (10.4%) versus 174 (14.1%) patients (0.74 [0.60-0.92], p=0.005). There were also reductions in readmission (451 [37%] vs 704 [57%]; 0.67 [0.62-0.72]), and revascularisation after the initial admission (92 [7.5%] vs 383 [31%]; 0.24 [0.20-0.30]). The results did not interact with the dalteparin/placebo allocation. INTERPRETATION: After 1 year in 100 patients, an invasive strategy saves 1.7 lives, prevents 2.0 non-fatal myocardial infarctions and 20 readmissions, and provides earlier and better symptom relief at the cost of 15 more patients with coronary-artery bypass grafting and 21 more with percutaneous transluminal angioplasty. Therefore, an invasive approach should be the preferred strategy in patients with unstable coronary-artery disease and signs of ischaemia on electrocardiography or raised levels of biochemical markers of myocardial damage.

[Early management of unstable coronary artery disease. Coronary angiography is the first measure in high-risk patients]. / Tidigt handläggande av instabil kranskärlssjukdom. Kranskärlsröntgen i första hand för högriskpatienter.

Unstable coronary artery disease is currently the major cause of admissions to coronary intensive care units, accounting for 30-40 per cent of cases. The underlying cause is rupture of an atherosclerotic plaque, coronary blood flow being impeded by a superimposed thrombus. New and more effective antithrombotic drugs are becoming increasingly available. Simultaneous early coronary angioplasty, stenting or bypass surgery provide the most effective amelioration of symptoms. Early revascularisation has not hitherto been found to reduce the risk of myocardial infarction or mortality in patients without signs of severe ischaemia. In this large category of cardiac patients, treatment strategy selection is of considerable importance to the effective utilisation of resources.

Lower threshold for adenosine-induced chest pain in patients with angina and normal coronary angiograms.

OBJECTIVE: To investigate whether patients with angina-like chest pain and normal coronary angiograms are more sensitive to adenosine as an inducer of chest pain. DESIGN: Increasing doses of adenosine were given in a single blind study as intravenous bolus injections. Chest pain and the electrocardiographic findings were noted. PATIENTS: Eight patients with angina-like chest pain but no coronary stenoses (group A), nine patients with angina and coronary stenoses (group B), and 16 healthy volunteers (group C). RESULTS: In the absence of ischaemic signs on the electrocardiogram adenosine provoked angina-like pain in all patients in groups A and B. The pain was located in the chest, and its quality and location were described as being no different from the patient's habitual angina. In group C, 14 of 16 subjects reported chest pain. The lowest dose resulting in chest pain was lower in group A (0.9 (0.6) mg) than in group B (3.1 (1.5)mg) (p < 0.005) and in group C (6.2 (3.7) mg) (p < 0.005). The maximum tolerable dose was lower in group A (4.7 (2.1) mg) than in group B (9.2 (3.8) mg) (p < 0.05) and in group C (12.0 (4.1) mg) (p < 0.005). CONCLUSIONS: Patients with angina-like chest pain and normal coronary angiograms have a low pain threshold and low tolerance to pain induced by adenosine.

Adenosine induced chest pain--a comparison between intracoronary bolus injection and steady state infusion.

OBJECTIVE: Adenosine may induce chest pain in at least two ways, either by direct stimulation of sensory afferents before actual ischaemia occurs or secondary to ischaemia. The aim was to study if the mechanism of pain induction may depend on the method of adenosine administration. METHODS: Increasing doses of adenosine were given to seven male patients with ischaemic heart disease referred for coronary angiography: first as a bolus intracoronary injection (2.5-50 mumol), second as a 1 ml.min-1 steady state infusion (0.01-20 mumol.min-1) and third as an intravenous steady state infusion (0.076-0.76 mumol.kg-1 x min-1). Pain, rate-pressure product, coronary sinus blood flow, and ECG were monitored. Lactate was analysed in coronary sinus and arterial blood. RESULTS: After intracoronary bolus injection there were no signs of myocardial ischaemia, whereas during intracoronary steady state infusion, and in spite of a lower, but definite, degree of pain, 5/7 patients showed myocardial lactate production and three patients showed ST depression. During the intravenous steady state infusion 6/6 patients showed ST depression. CONCLUSIONS: These findings suggest that when using adenosine for studies on the mechanisms of chest pain in patients with ischaemic heart disease it is preferable to use an intracoronary bolus injection technique rather than a steady state infusion, as the risk of inducing ischaemia with the latter model cannot be ignored.

Angina pectoris patients with normal coronary angiograms but abnormal thallium perfusion scan exhibit low myocardial and skeletal muscle energy charge.

Seven patients with angina pectoris and 201-thallium scintigraphy indicative of myocardial perfusion defects, but with normal coronary angiograms, were investigated. Metabolic events were studied in biopsies from myocardium and skeletal muscle (m. quadriceps femoris). Profound metabolic derangement was evidenced by a distinctly lowered energy charge in myocardium (0.88 +/- 0.04 in controls vs. 0.48 +/- 0.09 in patients; P less than 0.001) and skeletal muscle (0.92 +/- 0.01 in controls vs. 0.70 +/- 0.09 in patients; P less than 0.01). Accordingly, low values were recorded for ATP in both types of muscle, where ATP was lower than (myocardium) or the same as (skeletal muscle) ADP. The concentration of myocardial lactate was 115 +/- 74 mumol g-1 dry weight and that of skeletal muscle lactate was 11 +/- 3 mumol g-1 dry weight, compared to normal myocardial lactate of 18 +/- 10 mumol g-1 dry weight and normal skeletal muscle lactate of 11 +/- 3 mumol g-1 dry weight. Unprecedentedly low energy charge levels in both cardiac and skeletal muscle biopsies suggest that a systemic metabolic disease is highly probable. An inverse ATP/ADP ratio found in our patients is indicative of an aetiology different from ischaemia, which would not produce this relationship.