Search

Background: There is a paucity of real-world data assessing the association of operator volumes and mortality specific to primary percutaneous coronary intervention (PPCI)., Methods: Demographic, clinical and outcome data for all patients undergoing PPCI in Leeds General Infirmary, UK, between 1 January 2009 and 31 December 2011, and 1 January 2013 and 31 December 2013, were obtained prospectively. Operator volumes were analysed according to annual operator PPCI volume (low volume: 1-54 PPCI per year; intermediate volume: 55-109 PPCI per year; high volume: ≥110 PPCI per year). Cox proportional hazards regression analyses were undertaken to investigate 30-day and 12-month all-cause mortality, adjusting for confounding factors., Results: During this period, 4056 patients underwent PPCI, 3703 (91.3%) of whom were followed up for a minimum of 12 months. PPCI by low-volume operators was associated with significantly higher adjusted 30-day mortality (HR 1.48 (95% CI 1.05 to 2.08); p=0.02) compared with PPCI performed by high-volume operators, with no significant difference in adjusted 12-month mortality (HR 1.26 (95% CI 0.96 to 1.65); p=0.09). Comparisons between low-volume and intermediate-volume operators, and between intermediate and high-volume operators, showed no significant differences in 30-day and 12-month mortality., Conclusions: Low operator volume is independently associated with higher probability of 30-day mortality compared with high operator volume, suggesting a volume-outcome relationship in PPCI at a threshold higher than current recommendations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: recent studies report an age-dependent decline in mortality after acute myocardial infarction (AMI)., Objective: to investigate age-dependent improvements in survival after hospitalisation with AMI., Design: population-based cohort study using data from the Myocardial Ischaemia National Audit Project., Subjects: a total of 583,466 patients with AMI admitted to 247 hospitals between 1 January 2003 and 31 December 2010., Methods: six-month relative survival (RS) was calculated from the ratio of observed to expected survival using an age-, sex- and biennial year-matched population from the Office for National Statistics. Risk-adjusted mortality rates (RMAR) were estimated using shared frailty regression. Data were stratified by age group, AMI phenotype [(ST-elevation myocardial infarction, (STEMI) and non-STEMI, (NSTEMI)] and period of admission to hospital., Results: for STEMI, there was an increase in RS for patients aged 65-80 years (84.8 versus 89.2%) and those over 80 years (68.0 versus 71.8%), but not for patients aged 18 to <65 years (96.4 versus 96.9%). For NSTEMI patients aged 18 to <65 years RS was higher, but stable (95.5 versus 96.8%) and improved for patients aged 65-80 years (83.2 versus 88.5%) and patients aged >80 years (68.3% versus 75.5%). Likewise, RMAR improved for patients aged ≥65 years, were stable and higher for patients <65 years., Conclusions: there were significant improvements in survival after hospitalisation with AMI in the older but not younger patients. The scope for further reductions in mortality is likely to be much greater for older than younger patients with AMI., (© The Author 2013. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Acute coronary syndromes presenting with ST elevation are usually treated with emergency reperfusion/revascularisation therapy. In contrast current evidence and national guidelines recommend risk stratification for non ST segment elevation myocardial infarction (NSTEMI) with the decision on revascularisation dependent on perceived clinical risk. Risk stratification for STEMI has no recommendation. Statistical risk scoring techniques in NSTEMI have been demonstrated to improve outcomes however their uptake has been poor perhaps due to questions over their discrimination and concern for application to individuals who may not have been adequately represented in clinical trials. STEMI is perceived to carry sufficient risk to warrant emergency coronary intervention [by primary percutaneous coronary intervention (PPCI)] even if this results in a delay to reperfusion with immediate thrombolysis. Immediate thrombolysis may be as effective in patients presenting early, or at low risk, but physicians are poor at assessing clinical and procedural risks and currently are not required to consider this. Inadequate data on risk stratification in STEMI inhibits the option of immediate fibrinolysis, which may be cost-effective. Currently the mode of reperfusion for STEMI defaults to emergency angiography and percutaneous coronary intervention ignoring alternative strategies. This review article examines the current risk scores and evidence base for risk stratification for STEMI patients. The requirements for an ideal STEMI risk score are discussed.

Background: We investigated the association between diabetes mellitus (DM) and all-cause mortality in a large cohort of consecutive patients treated with primary percutaneous coronary intervention (PPCI) in the contemporary era., Methods: We conducted a retrospective analysis of a single-centre registry of patients undergoing PPCI for ST-segment elevation myocardial infarction (STEMI) at a large regional PCI centre between 2005 and 2009. All-cause mortality in relation to patient and procedural characteristics was compared between patients with and without DM., Results: Of 2586 patients undergoing PPCI, 310 (12%) had DM. Patients with DM had a higher prevalence of multi-vessel coronary disease (p<0.001) and prior myocardial infarction (p<0.001). Patients with DM were less commonly admitted directly to the interventional centre (p=0.002). Symptom-to-balloon (p<0.001) and door-to-balloon time (p=0.002) were longer in patients with DM. Final infarct-related-artery TIMI-flow grade was lower in patients with DM (p=0.031). All-cause mortality at 30 days (p=0.0025) and 1 year (p<0.0001) was higher in patients with DM. DM was independently associated with increased mortality after multivariate adjustment for potential confounders., Conclusions: Mortality remains substantially higher in patients with DM following reperfusion for STEMI in comparison with those without diabetes, despite contemporary management with PPCI. Greater co-morbidity, delayed presentation, longer times-to-reperfusion, and less optimal reperfusion may contribute to adverse outcomes.

Aims: To quantify the determinants of primary percutaneous coronary intervention (PCI) performance in England and Wales between 2004 and 2007., Methods and Results: All 8653 primary PCI cases admitted to acute hospitals in England and Wales as recorded in the Myocardial Ischaemia National Audit Project (MINAP) 2004-2007. We studied the impact of the volume of primary PCI cases (hospital volume) on door-to-balloon (DTB) times and the proportion of patients treated with primary PCI (hospital proportion) on 30-day mortality and employed regression analysis to identify reasons for DTB time variations with a multilevel component to express hospital variation. The proportion of patients receiving primary PCI increased from 5% in 2004 to 20% in 2007. Median DTB times reduced from 84 min in 2004 to 61 min in 2007. Median DTB times decreased as the number of primary PCI procedures increased. The 30-day all-cause mortality rate for hospitals performing primary PCI on >25% of ST-elevation myocardial infarction patients [5.0%; 95% confidence interval (CI): 3.9-6.1%] was almost double that of hospitals performing primary PCI on more than 75% (2.7%; 95% CI: 2.0-3.5%). Time-of-day, year of admission, sex, and diabetes significantly influenced DTB times. Hospital variation was evident by a hospital-level DTB time standard deviation of 12 min., Conclusions: There was a large variation in DTB times between the best and worst performing hospitals. Although patient-related factors impacted upon DTB times, the volume and proportion of patients undergoing primary PCI were significantly associated with delay and early mortality-hospitals with the highest proportion of primary PCI had the lowest mortality.

A 55-year-old lady underwent repeat aortic valve replacement using a 16-mm Carbomedics prosthesis. She made an uneventful postoperative recovery and now leads an unrestricted life. Doppler echocardiography reveals a 21-mm Hg gradient across the valve at rest. This did not increase with an infusion of 30 mcg/kg per min of dobutamine, which resulted in an increase in the cardiac output from 1.96 to 5.46 l/min.

Objective: To evaluate the role of haemostatic and haemodynamic variables in left atrial thrombosis in non-rheumatic atrial fibrillation., Design: Case-control study., Subjects: One hundred and nine patients with non-rheumatic atrial fibrillation., Interventions: Peak blood velocity measured at three sites in the left atrium. Venous blood sampled for coagulant proteins and markers of haemostatic activation., Main Outcome Measures: Presence of left atrial thrombus and spontaneous echo contrast at transoesophageal echocardiography., Results: Left atrial thrombus was identified in 19 patients (18%), 16 of whom had spontaneous echo contrast. Patients with thrombus had reduced peak left atrial appendage velocity compared with those without (0.17 v 0.26 m/s; P < 0.001), but no significant reductions in peak mid-left atrial or mitral valve outflow velocity. Patients with thrombus had increased plasma markers of platelet activation-beta thromboglobulin (56.8 v 30.4 IU/ml; P < 0.001) and platelet factor 4 (6.1 v 3.5 IU/ml; P < 0.01)-and of thrombogenesis: thrombin-antithrombin complexes (5.59 v 3.06 micrograms/ml; P < 0.001) and D-dimers (479 v 298 ng/ml; P < 0.01). von Willebrand factor was also increased (1.81 v 1.52 IU/ml; P < 0.05). A multiple logistic regression model identified left atrial appendage velocity (P = 0.001), beta thromboglobulin (P = 0.002), and von Willebrand factor (P = 0.04) as the independent associates of left atrial thrombosis, ahead of the presence of spontaneous echo contrast., Conclusions: Haemostatic and haemodynamic abnormalities are associated with left atrial thrombus in non-rheumatic atrial fibrillation, and may help stratify thromboembolic risk.

We examined the importance of a long plasma half-life (t1/2) on the antianginal effects of beta-blockade by comparing equivalent doses of once-daily atenolol 100 mg (t1/2 6-8 h) and betaxolol 20 mg (t1/2 20-22 h) in a double-blind placebo-controlled cross-over study of 20 patients with stable angina pectoris. At 20 h postdose, heart rate (HR) was lower with betaxolol than with atenolol whereas blood pressure (BP) was equally reduced by both drugs. Twenty-four-hour ambulatory HR recording demonstrated that this difference existed for the last 6 h of the dosage cycle. During treadmill exercise, HR remained lower with betaxolol than with atenolol and exercise time was significantly prolonged only by betaxolol. With placebo, radionuclide ventriculography demonstrated that left ventricular ejection fraction (LVEF) decreased during exercise. Betaxolol, but not atenolol, significantly attenuated the exercise-induced decrease in EF. Thus, the long plasma t1/2 of betaxolol is associated with a reduction in exercise-induced ischemia when tested toward the end of the 24-h dosage cycle. Plasma t1/2 therefore is of clinical relevance to the antianginal, but not antihypertensive, actions of beta-blockers.

Background: Healthy arteries exhibit endothelium-dependent dilation in response to both local acetylcholine and increased blood flow. In humans, clinically overt coronary artery disease is characterized by loss of dilation to both acetylcholine and blood flow. The temporal relation, however, between functional abnormalities of the endothelium and the development of atherosclerosis has not been established., Methods and Results: We examined endothelial vasodilator function in vivo at an early stage of the development of atherosclerosis. Two groups of seven Macaca fascicularis monkeys were studied; one group was fed a high cholesterol diet (0.73-1.0 mg cholesterol per calorie) for 11 months. Cholesterol feeding was associated with increased plasma cholesterol levels and with intimal thickening of the iliac arteries but with no reduction in luminal diameter. Endothelium-dependent vasomotor responses of the iliac arteries were then examined in vivo by quantitative contrast angiography. Acetylcholine produced significant dilation in the controls but paradoxical constriction in the group with early atherosclerosis (+9.0 +/- 3.2% versus -5.3 +/- 5.4%, p less than 0.05). In response to a twofold increase in blood flow achieved by administering adenosine distal to the arterial segment under examination, the controls again dilated, whereas the atherosclerotic group failed to dilate (+ 11.6 +/- 2.1% versus + 0.5 +/- 2.4%, p less than 0.05). Both groups, however, were able to dilate, and dilated equally, to the nonendothelium-dependent agent nitroglycerin (+ 13.7 +/- 4.8% versus + 19.1 +/- 4.3%, NS)., Conclusions: Endothelium-dependent vasodilation in response to both acetylcholine and increased blood flow may be lost early in the course of developing atherosclerosis before the appearance of stenosing and occlusive disease.

Background: We studied the effects on and possible interaction of balloon denudation and hypercholesterolemia on large arteries in the rabbit with special regard to structure and vascular reactivity., Methods and Results: New Zealand White rabbits fed a 1% cholesterol diet or a standard diet for 14 weeks underwent balloon denudation of the left iliac artery 4 weeks before death. Both the balloon-injured and the control iliac arteries were harvested for in vitro studies of vascular reactivity, for immunohistochemical staining with monoclonal antibodies directed at smooth muscle cells and macrophages, and for scanning electron microscopy. Balloon injury caused intimal smooth muscle proliferation with little macrophage infiltration and was followed by recovery of endothelium-dependent vasodilator function within 4 weeks. Hypercholesterolemia caused macrophage-rich lesions confined to the intima with moderate impairment of endothelial vasodilator function. Balloon injury in the setting of hypercholesterolemia caused intimal smooth muscle cell proliferation and intense macrophage infiltration throughout the arterial wall and severe impairment of endothelial vasodilator function. Scanning electron microscopy confirmed regrowth of the endothelium in all balloon-injured vessels. In the balloon-injured arteries of hypercholesterolemic animals, the regenerated endothelium exhibited areas of atypical morphology not seen after balloon injury or hypercholesterolemia alone., Conclusions: The present study shows that balloon injury, hypercholesterolemia, and their combination cause distinct lesions and functional disturbances. An arterial balloon injury in the setting of hypercholesterolemia produces a diffuse inflammatory response that is accompanied by a sustained impairment of endothelial function and a marked proliferative response.

Background: Previous studies have shown that little if any increase in heart rate occurs 1 minute before the onset of ischemia in ambulant patients with coronary artery disease. This study tested the hypothesis that there are characteristic relations between heart rate and ischemia in ambulant patients with coronary artery disease., Methods and Results: Twenty-one patients with proven coronary disease demonstrated 212 episodes of ischemia during 504 hours of continuous monitoring of the electrocardiogram. An important increase in heart rate (from 74 +/- 11 to 90 +/- 14 beats/min, p less than 0.001) occurred between 5 and 30 minutes (not 1 minute) before the onset of ischemia. A significantly higher heart rate at onset of ischemia was seen during Bruce protocol exercise testing than during daily life (117 +/- 12 versus 95 +/- 15 beats/min, p less than 0.01). However, when a less-strenuous, but more prolonged, exercise protocol was used in a subgroup of patients (n = 12), ischemia occurred at a heart rate that was significantly lower than during the Bruce protocol (88 +/- 14 versus 103 +/- 15 beats/min, p less than 0.05) and was not significantly different from the threshold heart rate at onset of ischemia during daily life (88 +/- 14 versus 84 +/- 12 beats/min, p = NS). As part of two placebo-controlled trials, treatment with both propranolol and nitroglycerin altered the distribution of ischemic events by heart rate but in opposite directions. Although propranolol largely eliminated events occurring at high (greater than 100 beats/min) and moderate (80-100 beats/min) heart rates, the number of events at low (less than 80 beats/min) heart rates was increased. In contrast, nitroglycerin reduced episodes at low and moderate heart rates only., Conclusions: Important increases in heart rate occur before the onset of ischemia during daily life, but this increase occurs much earlier than has been reported. Duration of heart rate increase appears to influence the heart rate threshold for ischemia, and this may contribute to the occurrence of ischemia at lower heart rates during daily life than during standard exercise testing. Last, different classes of drugs appear to have characteristic effects on ischemia occurring at different heart rates that may be useful in planning therapy.

Ventricular arrhythmias occur with increased frequency in both experimental and human cardiac hypertrophy. Although the process of hypertrophy itself may be arrhythmogenic, other factors may contribute to the high prevalence of arrhythmias in hypertensive patients with left ventricular hypertrophy (LVH). Disease of the large epicardial coronary arteries or of the small intramyocardial vessels (coronary microangiopathy) may lead to myocardial ischemia and thus predispose to arrhythmia. Myocardial fibrosis, a common sequelae of cardiac hypertrophy, has also been shown to be associated with ventricular arrhythmias in experimental models. Other possible determinants of ventricular arrhythmias in this group of patients include metabolic abnormalities; studies relating to the importance of hypokalemia in particular have yielded conflicting results. Thus a number of factors may combine to explain the high prevalence of ventricular arrhythmias in hypertensive patients with LVH.

Intracoronary acetylcholine produces endothelium-dependent dilation of normal coronary arteries and paradoxical constriction of atherosclerotic vessels. Regional differences in endothelium-dependent vasomotion, however, have not been studied in relation to the nonuniform development of atherosclerosis. We compared the vasomotor response to increasing doses of acetylcholine of angiographically smooth coronary artery segments prone to atherosclerosis (coronary branch points) with segments remote from branch points (straight segments). In patients with entirely smooth coronary arteries and a dilator response to acetylcholine (group 1, n = 7), branch points and straight segments demonstrated equal and significant dose-dependent dilation to acetylcholine (14.7 +/- 8.9% and 12.3 +/- 12.7%, respectively; p identical to NS). In patients with early atherosclerosis as manifest by luminal coronary irregularities, the lowest dose of acetylcholine (10(-8) M) produced constriction at branch points and slight dilation at straight segments (-6.3 +/- 7.4% vs. +2.2 +/- 7.3%, p less than 0.05). At higher doses of acetylcholine, both branch point and straight segments constricted, but constriction remained more pronounced at branch points. Both branch point and straight segments, however, retained the ability to dilate to the non-endothelium-dependent agent, nitroglycerin. In a third group of patients with angiographically entirely smooth coronary arteries but without dilation to acetylcholine, constriction to acetylcholine again occurred first at branch points. Thus, coronary branch points demonstrate increased sensitivity to acetylcholine-induced constriction in patients with angiographic evidence of early coronary atherosclerosis and in middle-aged patients with smooth coronary arteries. These segments, however, retain the ability to dilate to nitroglycerin. Whether this early evidence of defective endothelium-dependent vasodilation predicts the later development of occlusive atherosclerosis is not yet known.

This study investigated the vasodilator function of endothelium that regenerated after balloon angioplasty and the relation of this function to the extent of vascular injury and to subsequent intimal proliferation. Balloon angioplasty was performed in the left iliac artery of 47 New Zealand White rabbits. Vascular responses were examined in vitro 2 and 4 weeks after a "severe" injury (3.0-mm balloon) or a "moderate" injury (2.5-mm balloon). Both degrees of balloon injury caused complete endothelial denudation. Endothelial regrowth 2 weeks after either injury was confirmed histologically. Although the regenerated cells had irregular sizes and polygonal shapes and lacked the typical alignment in the direction of blood flow, immunocytochemical staining for factor VIII-related antigen identified these cells as endothelium. To study the vasodilator function of regenerated endothelium, rings of balloon-injured and control (contralateral) iliac arteries were suspended in organ chambers for recording of isometric force. Endothelium-dependent relaxation of balloon-injured vessels to acetylcholine and to the calcium ionophore A23187 were reduced at 2 and at 4 weeks after severe injury. After moderate injury, endothelium-dependent relaxations to these agents were reduced at 2 weeks but had normalized by 4 weeks. Endothelium-independent relaxation to sodium nitroprusside, however, was preserved in all study groups. Morphometric analysis revealed an inverse correlation between the degree of intimal thickening and maximal relaxation to acetylcholine (r = 0.45, p less than 0.01). Thus, there is a persistent attenuation of receptor- and nonreceptor-mediated endothelium-dependent relaxations after arterial injury. The regenerated cells have an altered morphological appearance, but staining for factor VIII-related antigen confirms their endothelial origin. The degree and duration of endothelial dysfunction depends on the severity of the initial injury and is related to the extent of intimal thickness.

In animals, acetylcholine dilates normal arteries and produces vasoconstriction in the presence of hypercholesterolemia, hypertension, or atherosclerosis, reflecting endothelial cell dysfunction. In patients with angiographically smooth coronary arteries, acetylcholine has been reported to produce both vasodilation and constriction. To test the hypothesis that the acetylcholine response relates to risk factors for coronary artery disease, acetylcholine 10(-8) to 10(-6) M was infused into the left anterior descending or circumflex coronary artery, and diameter changes were assessed with quantitative angiography in 34 patients with angiographically smooth coronary arteries. The acetylcholine response ranged from +37% (dilation) to -53% (constriction) at the peak acetylcholine dose. All coronary arteries dilated in response to nitroglycerin (26 +/- 17%), suggesting an abnormality of endothelial function in the patients with a constrictor response to acetylcholine. By multiple stepwise regression analysis, serum cholesterol (p less than 0.01), male gender (p less than 0.001), family history (p less than 0.05), age (p less than 0.05), cholesterol level (p less than 0.01), and total number of risk factors (p less than 0.0001) were independently associated with the acetylcholine response. Thus, coronary risk factors are associated with loss of endothelium-dependent vasodilation. The development of vasoconstriction is likely to be an abnormality of endothelial function that precedes atherosclerosis or an early marker of atherosclerosis not detectable by angiography.

Celiprolol (400 mg) and atenolol (100 mg) were given once a day to 16 patients with stable angina pectoris in a double blind placebo controlled crossover study. Celiprolol produced less suppression of heart rate both at rest and during exercise than atenolol. Both drugs were equally effective in reducing the frequency of angina and in delaying the onset of ischaemia during exercise. Radionuclide ventriculography showed that atenolol but not celiprolol lowered cardiac output at rest and during exercise. Thus the ancillary properties of celiprolol, including partial beta 2 agonist activity and direct vasodilating activity, have detectable effects on cardiac function that may be beneficial in patients with angina.