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ObjectivesTo investigate the impact of a CT-first strategy on all-cause and cardiovascular mortality in patients presenting with chest pain in outpatient cardiology clinics.MethodsPatients with a first presentation of suspected angina pectoris were identified and their data linked to the registrations of Statistics Netherlands for information on mortality. The linked database consisted of 33 068 patients. CT-first patients were defined as patients with a CT calcium score and coronary CT angiography, within 6 weeks after their initial visit. Propensity score matching (1:5) was used to match patients with and without a CT-first strategy. After matching, 12 545 patients were included of which 2308 CT-first patients and 10 237 patients that underwent usual care.ResultsMean age was 57 years, 56.3% were women and median follow-up was 4.9 years. All-cause mortality was significantly lower in CT-first patients (n=43, 1.9%) compared with patients without CT (n=363, 3.5%) (HR: 0.51, 95% CI 0.37 to 0.70). Furthermore, CT-first patients were more likely to receive cardiovascular preventative and antianginal medication (aspirin: 44.9% vs 27.1%, statins: 48.7% vs 30.3%, beta-blockers: 37.8% vs 25.5%, in CT-first and without CT-first patients, respectively) and to undergo downstream diagnostics and interventions (coronary interventions: 8.5% vs 5.7%, coronary angiography: 16.2% vs 10.6% in CT-first and without CT-first patients, respectively).ConclusionsIn a real-world regular care database, a CT-first strategy in patients suspected of angina pectoris was associated with a lowering of all-cause mortality.

ObjectiveEvidence on sex differences in outcomes after developing coronary heart disease (CHD) has focused on recurrent CHD, all-cause mortality or revascularisation. We assessed sex disparities in subsequent major adverse cardiovascular events (MACE) in adults surviving their first-time CHD.MethodsUsing a population-based cohort obtained from the Clinical Practice Research Datalink (CPRD GOLD) linked to hospitalisation and death records in the UK, we identified 143 702 adults (aged ≥18 years) between 1 January 1998 and 31 December 2017 with no prior history of MACE. MACE outcome was a composite of recurrent CHD, stroke, peripheral vascular disease, heart failure and cardiovascular-related mortality. Multivariable models (Cox and competing risks regressions) were used to assess differences between sexes.ResultsThere were 143 702 adults with any incident CHD (either angina, myocardial infarction or coronary revascularisation). Women (n=63 078, 43.9%) were older than men (median age, 73 vs 66 years). First subsequent MACE outcome was observed in 91 706 (63.8%). Women had a significantly lower risk of MACE (hazard ratio (HR), 0.68 (95% CI 0.67 to 0.69); sub-hazard ratio (HRsd), 0.71 (0.70 to 0.72), respectively) and recurrent CHD (n=66 543, 46.3%) (HR, 0.60 (0.59 to 0.61); HRsd, 0.62 (0.61 to 0.63)) when compared with men after incident CHD. However, women had a significantly higher risk of stroke (n=5740, 4.0%) (HR, 1.26 (1.19 to 1.33); HRsd, 1.32 (1.25 to 1.39)), heart failure (n=7905, 5.5%) (HR, 1.09 (1.04 to 1.15); HRsd, 1.13 (1.07 to 1.18)) and all-cause mortality (n=29 503, 20.5%) (HR, 1.05 (1.02 to 1.07); HRsd, 1.11 (1.08 to 1.13)).ConclusionsAfter incident CHD, women have lower risk of composite MACE and recurrent CHD outcomes but higher risk of stroke, heart failure, and all-cause mortality compared with men.

ObjectiveWomen with suspected angina without history of coronary artery disease (CAD) less frequently have flow-limiting stenosis (FL-CAD) and more often have microvascular disease, affecting predictive accuracy of stress echocardiography (SE) for detection of FL-CAD. We postulated that carotid plaque burden (CPB) assessment would improve detection of FL-CAD and risk stratification.MethodsConsecutive consenting patients assessed by SE on clinical grounds for new-onset chest pain also underwent simultaneous carotid ultrasound. Patients were followed for major adverse events (MAE): all-cause mortality, non-fatal myocardial infarction and unplanned revascularisation. Carotid plaque presence and burden (CPB) were assessed.ResultsAfter a mean of 2617±469 days (range 17–3740), of 591 recruited patients, 573 (97%) outcome data (314 females) were obtainable. Despite lower pretest probability of CAD in females versus males (14.9±0.8 vs 20.5±1.3, respectively, pConclusionIn females with new-onset stable angina without a history of cardiovascular disease, CPB improved the predictive accuracy of myocardial ischaemia for flow-limiting CAD. However, CPB provided incremental risk stratification in both sexes.

IntroductionThere is conflicting evidence regarding the benefits of percutaneous coronary intervention (PCI) in patients with grey zone fractional flow reserve (GZFFR artery) values (0.75–0.80). The prevalence of ischaemia is unknown. We wished to define the prevalence of ischaemia inGZFFR artery and assess whether PCI is superior to optimal medical therapy (OMT) for angina control.MethodsWe enrolled 104 patients with angina with 1:1 randomisation to PCI or OMT. The artery was interrogated with a Doppler flow/pressure wire. Patients underwent Magnetic Resonance Imaging (MRI) with follow-up at 3 and 12 months. The primary outcome was angina status at 3 months using the Seattle Angina Questionnaire (SAQ).Results104 patients (age 60±9 years), 79 (76%) males and 79 (76%) Left Anterior Descending (LAD) stenoses were randomised. Coronary physiology and SAQ were similar. Of 98 patients with stress perfusion MRI data, 17 (17%) had abnormal perfusion (≥2 segments with ≥25% ischaemia or ≥1 segment with ≥50% ischaemia) in the targetGZFFR artery. Of 89 patients with invasive physiology data, 26 (28%) had coronary flow velocity reserve GZFFR artery. After 3 months of follow-up, compared with patients treated with OMT only, patients treated by PCI and OMT had greater improvements in SAQ angina frequency (21 (28) vs 10 (23); p=0.026) and quality of life (24 (26) vs 11 (24); p=0.008) though these differences were no longer significant at 12 months.ConclusionsNon-invasive evidence of major ischaemia is uncommon in patients withGZFFR artery. Compared with OMT alone, patients randomised to undergo PCI reported improved symptoms after 3 months but these differences were no longer significant after 12 months.Trial registration numberNCT02425969.

A 23-year-old man of Asian origin presented with history of palpitations on exertion for the past 1 year, associated with mild exertional dyspnoea. There was no history of angina, syncope, ongoing fever or cachexia. There was history of prolonged febrile illness 2 years back lasting nearly 2 months, of which no details were available, apart from the fact that he was treated with intravenous drugs for nearly 6 weeks followed by antituberculous therapy for 6 months. There was no history of chest trauma or surgery. There was no history of congenital heart disease or acute rheumatic fever in the past. Clinical examination revealed …

The adverse consequences of stable coronary artery disease (CAD) are death, myocardial infarction (MI) and angina. Trials in stable CAD show that percutaneous coronary intervention (PCI) does not reduce mortality. PCI does appear to reduce spontaneous MI rates but at the expense of causing some periprocedural MI. Therefore, the main purpose of PCI is to relieve angina. Indeed, patients and physicians often choose PCI rather than first attempting to control symptoms with anti-anginal medications as recommended by guidelines. Nevertheless, it is unclear how effective PCI is at relieving angina. This is because, whereas anti-anginal medications are universally required to be tested against placebo, there is no such requirement for procedural interventions such as PCI. The first placebo-controlled trial of PCI showed a surprisingly small effect size. This may be because it is overly simplistic to assume that the presence of a stenosis and inducible ischaemia in a patient means that the clinical chest pain they report is caused by ischaemia. In this article, we review the evidence base and argue that if we as a medical specialty wish to lead the science of procedures for symptom control, we should recognise the special merit of placebo-controlled experiments.

ObjectiveThe National Institute for Health and Care Excellence (NICE) clinical guidelines ‘chest pain of recent onset: assessment and diagnosis’ (update 2016) state CT coronary angiography (CTCA) should be offered as the first-line investigation for patients with stable chest pain. However, the current provision in the UK is unknown. We aimed to evaluate this and estimate the requirements for full implementation of the guidelines including geographical variation. Ancillary aims included surveying the number of CTCA-capable scanners and accredited practitioners in the UK.MethodsThe number of CTCA scans performed annually was surveyed across the National Health Service (NHS). The number of percutaneous coronary interventions performed for stable angina in the NHS in 2015 was applied to a model based on SCOT-HEART (CTCA in patients with suspected angina due to coronary heart disease: an open-label, parallel-group, multicentre trial) data to estimate the requirement for CTCA, for full guideline implementation. Details of CTCA-capable scanners were obtained from manufacturers and formally accredited practitioner details from professional societies.ResultsAn estimated 42 340 CTCAs are currently performed annually in the UK. We estimate that 350 000 would be required to fully implement the guidelines. 304 CTCA-capable scanners and 198 accredited practitioners were identified. A marked geographical variation between health regions was observed.ConclusionsThis study provides insight into the scale of increase in the provision of CTCA required to fully implement the updated NICE guidelines. A small specialist workforce and limited number of CTCA-capable scanners may present challenges to service expansion.

A single assessment of psychological distress, which includes depression and anxiety, has been associated with increased mortality in patients with coronary heart disease, but the prognostic importance of persistence of distress symptoms is less certain.To determine whether intermittent and/or persistent psychological distress is associated with long-term cardiovascular (CV) and total mortality in patients with stable coronary artery disease.950 participants in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial completed at least four General Health Questionnaires (GHQ-30) at baseline and after ½, 1, 2 and 4 years. In a landmark analysis from 4 years, Cox proportional hazards models evaluated the risk of CV and total mortality by increasing levels of psychological distress: never distressed, sometimes any severity (GHQ score5), persistent mild (GHQ score5 on three or more occasions) and persistent moderate distress (GHQ score10) on three or more occasions, over a median of 12.1 (IQR 8.6-12.5) years. The models were both unadjusted and adjusted for known baseline risk factors.Persistent moderate or greater psychological stress was reported on three or more assessments by 35 (3.7%) subjects. These patients had a higher risk of both CV death (adjusted HR 3.94, 95% CI 2.05 to 7.56, p0.001) and all-cause mortality (adjusted HR 2.85, 95% CI 1.74 to 4.66, p0.001) compared with patients with no distress. In contrast, patients who reported persistent mild distress (n=73, 7.7%) on three or more visits, and those who met criteria for distress on only one or two assessments (n=255, 26.8%), did not have an increased risk of CV or all-cause mortality during follow-up.In patients with stable coronary artery disease, persistent psychological distress of at least moderate severity is associated with a substantial increase in CV and all-cause mortality.

In the 2016 update of the stable chest pain guideline, the National Institute for Health and Care Excellence (NICE) has made radical changes to the diagnostic paradigm that it—like other international guidelines—had previously placed at the centre of its recommendations. No longer are quantitative assessments of the disease probability considered necessary to determine the need for diagnostic testing and the choice of test. Instead, the recommendation is for no diagnostic testing if chest pain is judged to be ‘non-anginal’ and CT coronary angiography (CTCA) in patients with ‘typical’ or ‘atypical’ chest pain with additional perfusion imaging only if there is uncertainty about the functional significance of coronary lesions. The new emphasis on anatomical—as opposed to functional—testing is driven in large part by cost-effectiveness analysis and despite inevitable resource implications NICE calculates that annual savings for the population of England will be significant. In making CTCA the default diagnostic testing strategy in its updated chest pain guideline, NICE has responded emphatically to calls from trialists for CTCA to have a greater role in the diagnostic pathway of patients with suspected angina.

BackgroundIn patients with suspected angina pectoris, CT coronary angiography (CTCA) clarifies the diagnosis, directs appropriate investigations and therapies, and reduces clinical events. The effect on patient symptoms is currently unknown.MethodsIn a prospective open-label parallel group multicentre randomised controlled trial, 4146 patients with suspected angina due to coronary heart disease were randomised 1:1 to receive standard care or standard care plus CTCA. Symptoms and quality of life were assessed over 6 months using the Seattle Angina Questionnaire and Short Form 12.ResultsBaseline scores indicated mild physical limitation (74±0.4), moderate angina stability (44±0.4), modest angina frequency (68±0.4), excellent treatment satisfaction (92±0.2) and moderate impairment of quality of life (55±0.3). Compared with standard care alone, CTCA was associated with less marked improvements in physical limitation (difference −1.74 (95% CIs, −3.34 to −0.14), p=0.0329), angina frequency (difference −1.55 (−2.85 to −0.25), p=0.0198) and quality of life (difference −3.48 (−4.95 to −2.01), pConclusionsWhile improving diagnosis, treatment and outcome, CTCA is associated with a small attenuation of the improvements in symptoms and quality of life due to the detection of moderate non-obstructive coronary artery disease.Trial registration number:NCT01149590.

Forty years since Andreas Gruentzig performed the first percutaneous coronary intervention (PCI), the rationale for revascularisation in stable coronary artery disease (CAD) continues to evolve. The cardiology community has shifted from revascularisation of all anatomically obstructive lesions towards deferring and medically managing stenoses with preserved flow as measured by fractional flow reserve (FFR). Clinical trials have established the role of FFR in contemporary therapeutic decision making, with FFR-guided revascularisation associated with a reduction in the incidence of myocardial infarction, improved angina relief compared with optimal medical therapy (OMT) and reduced healthcare costs.1 2 ​Decision making in modern medicine is often driven by binary cut-offs, a strategy that has both strengths and limitations. On one hand, a binary cut-off can facilitate decision making and ease of interpretation, and therefore encourages the use of intracoronary physiology in clinical practice. In contrast, the use of a rigid cut-off does not account for the biological and measurement variability of FFR, thereby introducing a degree of inaccuracy around the diagnostic threshold. Initially an FFR value of 99% positive predictive value for inducible myocardial ischaemia across multiple non-invasive modalities.3 4 Given the observation that in a small proportion of lesions an FFR between 0.75 and 0.80 was associated with flow-limiting stenosis, the FFR threshold to guide revascularisation in the FAME trials was increased to 0.80 to improve its sensitivity in detecting ischaemia at the cost of specificity.2 Accordingly, an FFR grey zone for values between 0.75 and 0.80 was recommended in which decision making should be based on clinical judgement and the presence of additional information.1 Yet using binary cut-off values in interpreting FFR goes beyond diagnostic accuracy and has implications for its prognostic value. Previous …

In patients undergoing primary percutaneous intervention (PCI) for ST-elevation myocardial infarction (STEMI), about 10% also have a chronic total occlusion (CTO) of a non-culprit coronary artery. It remains controversial whether PCI of the CTO vessel, in addition to the culprit vessel, improves clinical outcome. The results of the randomised Evaluating Xience and left ventricular function in PCI on occlusiOns afteR STEMI (EXPLORE) study of 302 STEMI patients with successful PCI of the culprit vessel are reported in this issue of Heart. 1 Overall, there was no difference in major adverse cardiac events (MACE) at a median follow-up of 3.9 years in those with or without PCI of the CTO vessel (13.5% vs 12.3%, HR 1.03, 95% CI 0.54 to 1.98; p=0.93, figure 1). Although all-cause mortality did not differ between groups, cardiac mortality was higher with CTO-PCI (6.0% vs 1.0%, p=0.02). More patients with CTO-PCI were free of angina at 1 year (6.0% vs 1.0%, p=0.02) but his difference was not sustained on longer term follow-up. Overall, CTO-PCI in the setting of STEMI was not associated with a reduction in MACE, improvement in ventricular function or sustained reduction in symptoms. Figure 1 Clinical effect of early CTO-PCI vs CTO-no PCI on MACE in patients with ST-elevation myocardial infarction with a concurrent CTO: long-term follow-up. Kaplan-Meier estimates of the cumulative event rate of the composite end point of MACE: cardiac death, CABG and MI. Analyses were performed on a intention-to-treat basis. CTO, chronic total …

The 2016 National Institute for Health and Care Excellence (NICE) guidelines for the assessment of suspected stable angina recommend diagnosis with computed tomographic coronary angiography (CTCA), but this approach remains controversial. In a study in this issue of Heart ,1 the key to optimal use of CTCA appears to be careful patient selection. Specifically, CTCA is most useful in patients with symptoms consistent with possible angina defined as meeting two or three of the following characteristics: constricting discomfort in the front of the chest, neck, shoulders, jaw, or arms; precipitated by physical exertion; and relieved by rest or nitroglycerin within about 5 min. Possible angina also includes patients with non-anginal chest pain who have an abnormal resting ECG. In a post-hoc analysis of the Scottish COmputed Tomography of the HEART (SCOT-HEART) trial, diagnostic certainty with CTCA was increased most in those with possible angina (relative risk (RR) 2.22 (95% CI 1.91 to 2.60), P

Fractional flow reserve (FFR) has been suggested to have value in acute coronary syndromes (ACSs). The clinical and prognostic value of ischaemia reduction assessed by post-percutaneous coronary intervention (PCI) FFR has not been studied in this population.Consecutive stable ischaemic heart disease (SIHD) (N=390) and patients with ACS (N=189) who had pre-PCI FFR and post-PCI FFR were followed for 2.4±1.5 years. Primary endpoint was major adverse cardiac events (MACE) (composite of myocardial infarction, target vessel revascularisation and death).In patients with ACS, PCI led to significant improvement in FFR from 0.62±0.15 to post-PCI FFR 0.88±0.08 (p0.0001). Post-PCI FFR identified 29 patients (15%) who had persistently low FFR0.80 (0.75±0.06) despite angiographically optimal results prompting subsequent interventions improving repeat FFR (0.85±0.06; p0.0001). The difference in MACE events between patients with ACS and patients with SIHD varied according to the post-PCI FFR value (interaction p=0.044). Receiver operator curve analysis identified a final FFR cut-off of ≤0.91 as having the best predictive accuracy for MACE in the ACS study population (30% vs 19%; p=0.03). Patients with ACS achieving final FFR of0.91 had similar outcomes compared with patients who had SIHD (19% vs 16%; p=0.51). However, in patients with final FFR of ≤0.91 there was increased MACE versus patients with SIHD (30% vs 16%; p0.01).Post-PCI FFR is valuable in assessing the functional outcome of PCI in patients with ACS. Use of post-PCI FFR in patients with ACS allows for functional optimisation of PCI results and is predictive of long-term outcomes in patients with ACS.

Objective For percutaneous coronary intervention (PCI) to the unprotected left main stem (UPLMS), there are limited long-term outcome data. We evaluated 5-year survival for UPLMS PCI cases taking into account background population mortality. Methods A population-based registry of 10 682 cases of chronic stable angina (CSA), non-ST-segment elevation acute coronary syndrome (NSTEACS), ST-segment elevation myocardial infarction with (STEMI+CS) and without cardiogenic shock (STEMI−CS) who received UPLMS PCI from 2005 to 2014 were matched by age, sex, year of procedure and country to death data for the UK populace of 56.6 million people. Relative survival and excess mortality were estimated. Results Over 26 105 person-years follow-up, crude 5-year relative survival was 93.8% for CSA, 73.1% for NSTEACS, 77.5% for STEMI−CS and 28.5% for STEMI+CS. The strongest predictor of excess mortality among CSA was renal failure (EMRR 6.73, 95% CI 4.06 to 11.15), and for NSTEACS and STEMI−CS was preprocedural ventilation (6.25, 5.05 to 7.75 and 6.92, 4.25 to 11.26, respectively). For STEMI+CS, the strongest predictor of excess mortality was preprocedural thrombolysis in myocardial infarction (TIMI) 0 flow (2.78, 1.87 to 4.13), whereas multivessel PCI was associated with improved survival (0.74, 0.61 to 0.90). Conclusions Long-term survival following UPLMS PCI for CSA was high, approached that of the background populace and was significantly predicted by co-morbidity. For NSTEACS and STEMI−CS, the requirement for preprocedural ventilation was the strongest determinant of excess mortality. By contrast, among STEMI+CS, in whom survival was poor, the strongest determinant was preprocedural TIMI flow. Future cardiovascular cohort studies of long-term mortality should consider the impact of non-cardiovascular deaths.

The prevalence of angina is high in the general population, and increases with age in both sexes. Little consensus exists about which test is preferable when one is required for diagnosis, including significant differences in the current US and European guidelines. However, the recent PROMISE and SCOT-HEART trials incorporating the use of CCTA have demonstrated that an anatomical strategy is a reasonable alternative initial approach to use in intermediate-risk patients with stable chest for the diagnosis of IHD. Contemporary approaches should therefore consider both functional and anatomical strategies in an integrated decision-making model.

Objective To assess the cost-effectiveness of cardiac CT compared with exercise stress testing (EST) in improving the health-related quality of life of patients with stable chest pain. Methods A cost–utility analysis alongside a single-centre randomised controlled trial carried out in Northern Ireland. Patients with stable chest pain were randomised to undergo either cardiac CT assessment or EST (standard care). The main outcome measure was cost per quality adjusted life year (QALY) gained at 1 year. Results Of the 500 patients recruited, 250 were randomised to cardiac CT and 250 were randomised to EST. Cardiac CT was the dominant strategy as it was both less costly (incremental total costs −£50.45; 95% CI −£672.26 to £571.36) and more effective (incremental QALYs 0.02; 95% CI −0.02 to 0.05) than EST. At a willingness-to-pay threshold of £20 000 per QALY the probability of cardiac CT being cost-effective was 83%. Subgroup analyses indicated that cardiac CT appears to be most cost-effective in patients with a likelihood of coronary artery disease (CAD) of 60%. Conclusions Cardiac CT is cost-effective compared with EST and cost-effectiveness was observed to vary with likelihood of CAD. This finding could have major implications for how patients with chest pain in the UK are assessed, however it would need to be validated in other healthcare systems. Trial registration number (ISRCTN52480460); results.

Learning objectives The management of angina is determined by symptoms and cardiovascular risk, together guiding further assessment in order to detect significant underlying coronary artery disease (CAD). The current National Institute for Health and Care Excellence guidelines require that symptoms are precipitated by physical exertion to be defined as typical angina.1 There are, however, a number of other stressors that may induce myocardial ischaemia, including cold exposure2 and mental stress. In the first detailed description of angina pectoris in the medical literature in 1772, William Heberden noted “it is increased by disturbance of the mind”.3 Mental stress-induced myocardial ischaemia (MSIMI) is a recognised phenomenon, but in the absence of an evidence base it is not routinely explored during either the clinical consultation or subsequent investigations. Significant uncertainties remain; in particular, how does MSIMI differ from exercise-induced myocardial ischaemia, and does it hold any particular significance for patients with ischaemic heart disease? Numerous observational studies have suggested that exposure to both acute and chronic mental stress is associated with an increased incidence of adverse cardiac events. Natural disasters, including earthquakes4–7 and hurricanes,8 have been linked with increases in cardiac mortality immediately after the event. There was a 71% increase in cardiac deaths on the day of the Northridge earthquake and a 35% increase in hospital admissions for myocardial infarction over the ensuing week.5 Similar findings are reported with unnatural events including in civilian communities under threat of imminent missile attack9 and with major sporting competitions.10–13 During the 2006 FIFA World Cup in Germany, the incidence of acute cardiac events was 2.7 times higher on match days involving the German national team.14 In those known to have …

Coronary artery stenoses frequently cause chest pain and/or dyspnoea. The clinical challenge for a physician taking care of patients presenting for the first time with such symptoms is to find out the underlying cause by applying a straightforward and accurate diagnostic approach—which minimises use of personal and financial resources while achieving a conclusive and clinically helpful diagnosis. Since (1) the clinical picture of patients presenting with symptoms of chest pain and/or dyspnoea is multifaceted, and (2) the diagnostic armamentarium for work-up of suspected coronary artery disease (CAD) is steadily growing, an evidence based and profound knowledge of the diagnostic value and specific features/requirements of diagnostic tests is mandatory in order to choose the appropriate modality for the individual patient. Therefore, this article will focus of the pre-test assessment of clinical symptoms in patients with suspected CAD, and the subsequent selection of the most appropriate diagnostic modality for work-up of CAD. In simple terms, the symptom ‘angina pectoris’ (AP)—and/or the possible equivalent ‘dyspnoea’—occurs as the result of a mismatch between myocardial oxygen demand and supply; for example, it may be caused by an epicardial coronary artery stenosis leading to myocardial ischaemia in the respective myocardial territory distal to the stenosis. In a patient with ‘typical’ symptoms of AP, the discomfort is located retrosternally and occurs during exercise, since the aforementioned mismatch in oxygen demand/supply is increased in response to physical activity and is relieved either by stopping exercise or by administering vasodilating substances such as glyceryl trinitrate (nitroglycerine).1 In contrast, ‘atypical’ AP is defined as chest discomfort fulfilling two out of three conditions associated with ‘typical’ angina. If only one or none of these conditions is met, this is termed ‘non-anginal’ chest pain. ‘Atypical’ angina comprises retrosternal chest pain which occurs at rest and responds to acute nitrates. The clinical …

To the Editor Nestelberger et al 1 performed a prospective observational study of patients with left bundle branch block (LBBB) and suspected acute coronary syndrome (ACS) to further elucidate the optimal strategy of evaluation for this population. Unfortunately there are several methodological problems which prevent the authors from realising the full clinical potential of their dataset. First, the study uses the diagnosis of acute myocardial infarction (AMI) as the primary outcome against which the ECG findings are judged, implying both that the role of the ECG is to diagnose all types of AMI, and that the authors expect such accuracy. This logic runs counter to the role of …

Objective Determine whether remote ischaemic postconditioning (RIP) protects against percutaneous coronary intervention-related myocardial infarction (PCI-MI). Design Single-centre, randomised, blinded to the researchers, clinical trial. ClinicalTrials.gov (NCT 01113008). Setting Tertiary hospital centre. Patients 232 patients underwent elective PCI for stable or unstable angina. Interventions Patients were randomised to RIP (induction of three 5-min cycles of ischaemia in the arm after the PCI) versus placebo. Main outcome measures The primary outcome measure was the peak 24-h troponin I level. PCI-MI was defined by an elevation of troponin values >3 or >5 of the 99th percentile according to the classical or the new definition. The secondary outcome measure was hospital admission, PCI for stable angina or acute coronary syndrome and mortality after 1 year of follow-up. The use of RIP in diabetic patients was specifically studied. Results The mean age was 64.6 years, and 42% were diabetic. The peak troponin in the RIP patients was 0.476 vs 0.478 ng/mL (p=0.99). PCI-MI occurred in 36% of the RIP patients versus 30.8% in the placebo group (p=0.378). Diabetic RIP patients had more PCI-MI (new definition): OR 2.7; 95% CI 1.10 to 6.92; p=0.027. The secondary outcome measure was seen in 11.7% of the RIP patients versus 10.8% in the placebo group (p=0.907). Conclusions RIP did not reduce the damage associated with elective PCI or cardiovascular events during the follow-up. The diabetic population who underwent RIP had more PCI-MI.

To investigate the predictors and impact on long-term survival of one chronic total occlusion (CTO) or multiple CTOs in patients presenting with ST-elevation myocardial infarction (STEMI).Single-centre retrospective observational study.University-based tertiary referral centre.Between 2006 and 2011, a total of 2020 consecutive patients referred with STEMI were categorised into single vessel disease, multivessel disease (MVD) without CTO, with one CTO or with multiple CTOs.Primary percutaneous coronary intervention.The primary end-point was the 1-year mortality.The prevalence of single vessel disease, MVD without CTO, with one CTO or with multiple CTOs was 70%, 22%, 7.2% and 0.8%, respectively. Independent clinical predictors for the presence of CTO were cardiogenic shock (OR 5.05; 95% CI 3.29 to 7.64), prior myocardial infarction (OR 2.06; 95% CI 1.35 to 3.09), age65 years (OR 1.94; 95% CI 1.40 to 2.71) and history of angina (OR 1.94; 95% CI 1.29 to 2.87). Mortality was worse in patients with multiple CTOs (76.5%) compared with those with one CTO (28.1%) or without CTO (7.3%) (p0.0001). After adjustment for left ventricular ejection fraction and renal function, MVD was an independent predictor for 1-year mortality (HR: 1.81; 95% CI 1.18 to 2.77, p=0.007), but CTO was not (HR: 1.07; 95% CI 0.66 to 1.73, p=0.78).Simple clinical factors are associated with the presence of CTO in non-infarct-related artery in patients presenting with STEMI. In these patients, long-term survival was independently associated with MVD, left ventricular ejection fraction and renal function, but not with CTO per se.

Background Readmission following an acute coronary syndrome (ACS) is frequent in our community. Patient specific factors identifying those at risk of readmission are poorly described. Methods Data were analysed from 5219 patients with an ACS enrolled in the Australian and New Zealand population of the Global Registry of Acute Coronary Events (GRACE) between 1999 and 2007. Patients who were readmitted for cardiovascular disease within 6 months of discharge were identified; regression analysis was used to predict independent patient factors associated with readmission 1 month and 1–6 months after discharge. Results 1048 patients (20.1%) were readmitted within 6 months, with a significant proportion (n=434, 41.4%) of readmissions occurring within 30 days of discharge. Readmission within 6 months was associated with a higher incidence of unscheduled cardiac catheterisation (HR 25.64, 95% CI 18.41 to 35.71), unscheduled percutaneous coronary intervention (PCI) (HR 15.78, 95% CI 10.56 to 23.59), stroke (HR 1.92, 95% CI 1.08 to 3.43), and death (HR 2.40, 95% CI 1.66 to 3.49). Recurrent ischemia in hospital and a diagnosis of S-T elevation myocardial infarction during the index admission were associated with the strongest risk of early rehospitalisation, while revascularisation by PCI or coronary artery bypass surgery (CABG) was associated with lowest risk of early readmission. A history of heart failure, prior myocardial infarction or angina was associated with a greater likelihood of later rehospitalisation, whereas revascularisation by CABG was associated with the lowest risk of later rehospitalisation. Conclusions Several patient and clinical factors identify patients at higher risk of readmission. Identifying these factors and escalating in-hospital and post-discharge care for these higher risk patients may prevent readmission and improve outcome.

Most guidelines for treatment of hypertension including the Joint National Committee-7 recommend a blood pressure (BP) goal of140/90 mm Hg for hypertensive patients and a more aggressive goal of130/80 mm Hg for patients with coronary artery disease (CAD), based largely on expert consensus.To evaluate the BP targets in patients with CAD DATA SOURCES: PUBMED, EMBASE and CENTRAL Study Selection: Randomised clinical trials (RCTs) of antihypertensive therapy in patients with CAD, enrolling at least 100 patients, with achieved systolic pressure of=135 mm Hg in the 'intensive BP' group and=140 mm Hg in the 'standard BP' group with follow-up for at least 1 year and evaluating cardiovascular outcomes.The following efficacy outcomes were extracted- all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, angina pectoris, heart failure and revascularisation.We identified 15 RCTs enrolling 66,504 participants with 276,328 patient-years of follow-up. Intensive BP group (≤ 135 mm Hg) was associated with a 15% decrease in heart failure rate and 10% decrease in stroke rate, driven largely by trials with a more intensive BP group (≤ 130 mm Hg), with similar outcomes for death and cardiovascular death and was associated with a 105% increase in the risk of hypotension. More intensive BP group (≤ 130 mm Hg) was also associated with a reduction in myocardial infarction and angina pectoris. The results were similar in a Bayesian random effects model. In addition, lower seemed to be better (based on regression analysis) for the outcomes of myocardial infarction, stroke, heart failure and perhaps angina.The present body of evidence suggests that in patients with CAD, intensive systolic BP control to ≤ 135 mm Hg and possibly to ≤ 130 mm Hg is associated with a modest reduction in stroke and heart failure but at the expense of hypotension. Lower was better, although not consistently so for myocardial infarction, stroke, heart failure and perhaps angina. Further trials are needed to prove these findings.

The presence of angina pectoris (AP) in patients with either normal coronary angiograms or with non-obstructive coronary artery disease (CAD) is not only a frequent clinical finding but also a clinical and therapeutic challenge. Only recently, Patel et al evaluated the diagnostic yield of coronary angiography—regarding the presence or absence of obstructive CAD—among almost 400 000 patients with suspected CAD.1 Although the majority (70%) of these patients was suffering from chest pain symptoms, only 37.6% of them demonstrated obstructive CAD by invasive coronary angiography (defined as diameter stenosis >50% of the left main coronary artery or >70% of a major epicardial vessel). This surprising finding raises the following question: how should we explain the presence of AP symptoms (typical enough to motivate coronary angiography) in patients without obstructive CAD? Moreover, we need to consider the following clinical issues: (1) non-obstructed coronary arteries are also found in a sizeable subgroup of ≥10% of patients who undergo urgent coronary angiography due to angina accompanied by troponin elevation, and these patients represent a high risk group with a worse prognosis even in the absence of obstructive CADw1–w3; and (2) the presence of myocardial ischaemia in the absence of obstructive CAD still predicts cardiovascular outcome and is associated with higher rates of anginal hospitalisation, repeat catheterisation, and greater treatment costs.w4 Therefore, further evaluation of the underlying pathophysiology and potential treatment options in patients presenting with AP in the absence of obstructive CAD is a clinically highly relevant issue. In the following review, different (sometimes overlapping) pathophysiologies causing symptoms of AP in the absence of obstructive CAD are discussed, and current diagnostic as well as therapeutic options are illustrated. Obviously, hypertension is a frequent and important cardiovascular risk factor. As recently summarised by Raman et al ,2 hypertension is a predisposing …

The management of patients with stable angina presents clinicians and healthcare providers with a major clinical and health economic challenge. The Health Survey for England 2006 reported that around 8% of men and 3% of women aged between 55 and 64 years have or have had angina, and these figures rise to 14% and 8% respectively for men and women aged between 65 and 74 years.1 Large randomised trials suggest that people with stable angina have a good prognosis with an all-cause mortality of around 1.5% a year,2 but population-based studies have reported substantially higher annual cardiovascular death rates.3 4 Moreover, a diagnosis of angina has a significant impact on quality of life, which deteriorates progressively in proportion to the severity of symptoms.5 The Euro Heart survey of 3779 patients with a new diagnosis of stable angina disclosed considerable differences between participating countries in the prescription of anti-anginal drugs, use of non-invasive and invasive investigations and rates of myocardial revascularisation.6 This variation in practice reflects uncertainty about the appropriate management of patients with stable angina and highlights the need for evidence-based clinical guidelines. The recently published NICE clinical guideline (CG126) on the management of stable angina offers advice on treatment of episodes of angina, anti-anginal drug treatment, secondary prevention, the role of risk scores and non-invasive functional investigation, myocardial revascularisation, life-style adjustments and the management of refractory angina. Detailed review of the evidence for the guideline can be found in the full version (http://guidance.nice.org.uk/CG126) and this article summarises the most important recommendations (see box 1). Other NICE clinical guidelines deal with the diagnosis of …

In the Heart paper by Adamson et al ,1 the authors outline the diagnostic and prognostic benefits of CT coronary angiography (CTCA) in the context of the new 2016 National Institute for Health and Care Excellence (NICE) guidelines for evaluation of chest pain.2 This information, on how to maximise utility of CTCA while minimising unnecessary invasive angiography, is critical for physicians, patients and payors. While CTCA has been demonstrated to be more accurate than functional testing and prognostically superior, it has been burdened with a higher rate of invasive angiography, which has led some to discourage its use. The study by Adamson et al 1 proves, for probably the first time, that CTCA guideline-directed care can not only reduce future myocardial infarction, but not lead to an increase in the use of invasive angiography. The most important finding in this context is that individuals classified with possible angina derived large benefits from CTCA, while those with non-anginal chest pain did not. This provides critical reassurance that this test can assist clinicians in identifying patients that will derive the maximum benefit from CTCA, without increasing unnecessary invasive angiography. Direct visualisation of atherosclerosis with CTCA has always been a concept that made intuitive sense. The …

Background In over 50% of patients with angina, the underlying ischaemia is related to microvascular dysfunction (MVD), rather than epicardial coronary artery disease (CAD). Clinically, MVD remains a major diagnostic challenge, which hinders targeted therapy and confers impaired clinical outcomes. Myocardial perfusion reserve (MPR), as assessed by cardiovascular magnetic resonance (CMR), is impaired in those with microvascular angina. We sought to objectively diagnose microvascular ischaemia using CMR by defining an MPR cut-off, validated against invasive coronary microvascular physiology (Index of Microvascular Resistance, IMR). Methods 75 subjects (50 patients with angina and suspected CAD; 25 healthy controls) underwent CMR to assess LV function, MPR (adenosine stress/rest first-pass perfusion imaging) and viability (late gadolinium enhancement). All patients underwent invasive coronary angiography with pressure-wire assessment of IMR and fractional flow reserve (FFR). A total of 120 coronary arteries were assessed. CMR images were analysed by observers blinded to clinical and angiographic data. MPR was defined as the ratio of stress/rest myocardial signal intensity upslope gradients during gadolinium first-pass perfusion imaging, normalised to LV blood pool enhancement. Infarcted myocardium was identified using LGE and excluded from analysis. Results For reference, myocardium downstream of significant epicardial stenosis (FFR 0.8), non-infarcted myocardium had intermediate MPR: (unobstructed-CAD 1.6±0.4, obstructed-CAD 1.3±0.4; controls: 1.9±0.4, p 40: 1.3±0.4; all p 40 but unobstructed epicardial coronary arteries had equivalent MPR to ischaemic myocardium supplied by significant epicardial stenosis (1.3±0.4 vs 1.3±0.4, p=0.48, figure 1). Downstream of unobstructed epicardial coronary arteries of CAD patients, MPR 1.5 detected microvascular ischaemia (defined by IMR>40) with a sensitivity of 82%, specificity of 83%, and accuracy of 83% on ROC analysis (AUC 0.87±0.06, figure 2). Conclusions Microvascular ischaemia can be objectively diagnosed using CMR perfusion imaging. Reduced MPR is related to increased microvascular resistance, as validated by invasive IMR. The novel MPR criterion of 1.5, to detect high IMR>40, can confirm the clinical diagnosis of microvascular ischaemia, enabling targeted therapy and disease monitoring.

Introduction Refractory angina (RA) is a growing clinical problem due to improved survival from coronary artery disease (CAD) and an ageing population. These no option patients experience chronic angina-type pain, in the context of CAD, despite optimal medical and revascularisation therapies. Consequently, management of these patients is challenging and outcomes remain suboptimal. As mortality is no worse, the focus of treatment has shifted to improving symptoms, quality of life (QoL) and psychosocial outcomes. Methods We undertook a single-centre study of the impact of a multi-disciplinary care pathway (Figure 1) on psychosocial outcomes, QoL and changes in cardiovascular medications. We performed a retrospective search of Electronic Patient Records and databases at the Royal Brompton Hospital for all patients with RA seen between 23/01/2003 and 06/06/2016. Data collected included pre- and post-intervention Hospital Anxiety and Depression Scale and Seattle Angina Questionnaire scores, use of the Angina Plan, referral for specialist pain management and alterations in cardiovascular medications. Median scores and differences for anxiety, depression and QoL were analysed using Wilcoxon matched-pairs signed rank tests. Chi-squared tests were used to assess medication changes. Statistical significance was p Results A total of 190 patients with RA were included. The Angina Plan was used in 80.5% (n=153) and 38.9% (n=74) patients were referred to pain clinic. Comparison of pre- and post-intervention scores (Table 1) showed significant improvements in anxiety (p=0.0005), depression (p=0.0469), and QoL including physical limitation, frequency and perception of angina symptoms and treatment satisfaction (all p 0.05) (Table 2). Conclusions In this study, we showed that a multi-disciplinary care pathway for patients with RA can significantly improve psychosocial outcomes, QoL and medication use. Furthermore, the rate of use of the Angina Plan was high, emphasising the benefits of this specialist nurse-delivered cognitive behavioural therapy-based rehabilitation program in the management of RA. Conventional anti-anginal medication use was largely unchanged or reduced (52.8% of patients), in keeping with a non-cardiac aetiology for a proportion of patients symptoms. Ivabradine and ranolazine increased, associated with their introduction to the market. Few data demonstrate the potential impact of specialist services for patients with RA in improving QoL and psychosocial wellbeing, which are the management priorities in this challenging patient group. Our findings suggest that further work in this area is warranted.

Background Single photon emission computed tomography (SPECT) is a well-established method to evaluate patients with coronary artery disease (CAD). Myocardial contrast echocardiography (MCE) is an imaging technique that allows assessment of myocardial perfusion in a real-time setting. Very short term prognostic study has shown that vasodilator MCE is superior to SPECT for the prediction of hard events. We sought to investigate the long term prognostic value of SPECT and MCE in the assessment of patients with known or suspected CAD. Methods We retrospectively followed-up patients with suspected or known CAD who were scheduled for coronary angiography and who also underwent MCE and SPECT at our institute, as part of multicentre studies performed between January 2002 and December 2009. Rest and vasodilator SPECT was performed after injection of 99mTc-sestamibi using the standard technique on separate days. Coronary Angiography (CA) was performed within thirty days of stress imaging. We calculated the ratio of the number of abnormal segments (at rest and/or stress) to the total number of segments expressed as% for both MCE and SPECT in order to obtain a uniform assessment of the total ischaemic and scar burden (MCE and SPECT indexes). This population was followed up in 2016 to obtain a long term prognostic value of MCE and SPECT for hard events, all-cause mortality and non-fatal myocardial infarction (NFMI). Results Of the 277 patients who were analysed, 262 followed up and 15 were lost to follow up (5.4%). The mean age was 63.4 years and 186 (71.8%) patients were male, 82 (31.7%) had diabetes, 180 (69.5%) hypertension, 189 (73%) dyslipidaemia, 26 (10%) family history of CAD (FHCAD) and 64 (24.7%) were smokers. Prior CAD (angina, known acute myocardial infarction (AMI) or coronary revascularisation) was present in 178 (68.7%) patients, left ventricular systolic dysfunction in 32 (12.4%) and chronic kidney disease in 16 (6.2%). Over a mean follow-up period of 80 months(6.6 years)±6 months, 18 patients suffered NFMI and 29 died (18% hard events, annualised hard events 2.7%). Both MCE and SPECT indexes were significant predictors on univariate analysis for all-cause mortality (p=0.008 and p=0.035 respectively), but MCE index was the only independent predictor for hard events (HR 3.711, 95% CI(1.13–12.14), p=0.03). Figure 1 demonstrates the Kaplan-Meier curve for the long-term prognostic value in all-cause mortality and NFMI of abnormal versus normal MCE. The annualised event rate for the abnormal MCE is 3.8% versus 1.0% for the normal MCE. Conclusion This is the first study to our knowledge that investigated the long-term prognostic value of SPECT and MCE in patients with suspected or known CAD. MCE was the only independent predictor of hard events. These results further support the routine use of MCE and not SPECT for the long-term prognostication of patients with known or suspected CAD.

Background There is strong evidence of FFR guided treatment in multi-vessel disease. The presence of a concomitant CTO may influence the FFR measurement in donor vessel as suggested in previous studies and reports. This has an important implication on clinical decision making for complete revascularisation in patients with chronic total occlusion. We sought to investigate the influence of collateral regression after successful CTO recanalisation on donor vessel pressure-derived indices. Methods The study participants were patients with angina who had RCA CTO. 28 out of 34 consecutive patients underwent successful PCI to RCA CTOs during the study period and completed the follow study (at 3 months post CTO PCI) were included in this analysis. Coronary pressure-derived indices (resting PD/PA, iFR and FFR) were measured pre and post successful RCA CTO PCI in donor vessels and at follow up procedures. Results The mean age was 62.38 years. The mean estimated CTO duration was 238.72 weeks and CTO length was 32.44 mm. 25 patients had ischaemia and or viability in the RCA territory assessed with cardiac MRI. LAD was the major donor vessel in 24 patients and LCX was the minor donor vessel in 4 patients. Percent stenosis on QCA in the major and minor donor vessel were 40.6% and 35.1% respectively. The mean resting Pd/Pa, iFR and FFR pre and post RCA CTO PCI and at follow-up procedures in major donor vessel were (0.893, 0.862, 0.764), (0.907, 0.886, 0.753) and (0.918, 0.901, 0.787) respectively. The mean resting Pd/Pa, iFR and FFR pre and post RCA CTO PCI and at follow-up procedures in minor donor vessel were (0.979, 0.966, 0.890), (0.983, 0.979, 0.880) and (0.981, 0.974, 0.898) respectively. The changes in coronary pressure-derived indices pre and post RCA CTO PCI and at follow up procedures are summarised in table 1. In major donor vessel, there was significant changes in the difference between follow up and pre-CTO PCI values for Pd/Pa, iFR and FFR values (p values 0.006, 0.003 and 0.047 respectively). There was also significant change in the difference between follow up and post-CTO PCI FFR value (P value 0.002). FFR collateral reduced significantly at follow-up (p value 0.000). Conclusion Successful recanalisation of a RCA CTO results in increase in major donor vessel coronary pressure-derived indices at follow up procedure associated with the regression of collateral function. In patients with multi-vessel disease, the expected change and the optimal timing to perform PCI in donor vessel should be considered when planning multi-vessel revascularisation in this setting.

Introduction Readmission following a percutaneous coronary intervention (PCI) procedure is undesirable, being associated with patient morbidity and financial penalties. US data suggest 30 day readmission rates of approximately 10%, however little data is available within the UK. Reductions in the length of stay following PCI potentially increase the likelihood of early readmission. This study reviewed readmission’s following PCI undertaken in a non-surgical PCI centre in the UK. Methods Hospital admission databases were reviewed for all patients who had undergone a PCI at the centre. All patients who were readmitted to the Trust within 30 days of their PCI were identified, and a retrospective analysis was then undertaken of their hospital records. Results The data set comprised of 3754 patients who had all undergone at least one PCI procedure over the past 6 years. Of these, 409 patients (10.9%) were readmitted within 30 days. A significantly greater proportion of readmission’s within 30 days had an index PCI for acute coronary syndrome (ACS, 63.8% vs. 49.6%, p The average duration of time between the index PCI and readmission was 11.6 days, with a trend towards earlier presentation in those patients representing with a cardiac diagnosis (10.8 days vs. 12.2 days, p=0.09). Non-cardiac diagnoses were the greatest contributing diagnosis for all readmission’s, with non-cardiac chest pain, gastrointestinal reflux disease and bony injuries (as others) the commonest final diagnosis. Cardiac readmission’s accounted for 41.4% of all cases with angina and ACS the final diagnosis in 65.4% of patients. 61 patients (14.4%) had a repeat angiogram, with 31 leading to no change in treatment. 18 patients underwent an admission which led to a non-target vessel revascularisation, and 12 patients a target vessel revascularisation. The commonest treatments were no change in medication (41.4%), changes to non-cardiac medication (11.4%) and changes to anti-anginal medication (11.2%). Cardiac readmission’s had a greater rate of mortality at twelve months (2.9% vs. 0.8%, p=0.29). Conclusion Cardiac readmission’s continue to occur after 10% of percutaneous coronary intervention procedures. Whilst the prognosis is good, measures to reduce these rates are required.

This journal reports an analysis of symptoms and quality of life (QOL) of patients enrolled in the Scottish COmputed Tomography of the HEART (SCOT-HEART).1 Last year the results of the two major trials on cardiovascular imaging strategies for the diagnosis of coronary artery disease (CAD) were published (ie, PROMISE/PROspective Multicenter Imaging Study for Evaluation of chest pain—performed in North America and SCOT-HEART—performed in Scotland).2–4 They were structured to analyse the impact of cardiac CT (CCT) on current standards of care. The PROMISE trial ultimately showed a diagnostic and prognostic equivalence of anatomical strategy versus the North American standard of care; although more patients in the CCT group underwent cardiac catheterisation within 3 months after randomisation, the secondary end point of the frequency of catheterisation showing no obstructive CAD was significantly lower in the CCT group. The SCOT-HEART investigated the incremental value of CCT on top of a European standard of care. The end point was certainty of the diagnosis of angina secondary to coronary heart disease at 6 weeks, while long-term outcomes were major adverse cardiovascular events. Most patients underwent stress ECG (85%) and a third underwent other stress imaging tests. CCT improved diagnosis, treatment and outcome of symptomatic stable patients with suspected CAD. The improvement was associated with better selection of patients for invasive coronary angiography, more appropriate changes in therapy, and a halving in the rates of fatal and …

Amiodarone was initially developed in the early 1960s as a treatment for angina pectoris, since it produces coronary vasodilation and decreases cardiac oxygen demand. However, its pronounced antiarrhythmic effects redirected its use and amiodarone has become a widely used class III anti-arrhythmic drug. Compared to other antiarrhythmic drugs, it is more effective in treating both supraventricular and ventricular arrhythmias.1 It has few negative inotropic effects. The use of amiodarone is, however, limited by the relative frequent occurrence of serious and potentially life threatening side effects. Because of these side effects, generally it is not the drug of first choice in the treatment of arrhythmias. Amiodarone is an iodine-rich drug with strong structural similarities to the thyroid hormones (figure 1).2 After oral intake, absorption is limited (30–50%). When absorbed, it is metabolised in the liver to produce the active metabolite desethyl-amiodarone. Due to its lipophilic nature, it has strong tissue affinity and a large volume of distribution. In chronic users, high concentrations are found in fatty tissue, liver and lung and somewhat lower concentrations in kidney, heart, skeletal muscle, thyroid gland and brain. The distribution to these tissues is relatively slow, requiring high initial loading doses. Due to the relatively slow distribution, a steady state of tissue concentrations is reached only after 2 months. The relation between serum concentrations and clinical effect is not very clear. Serum concentrations >2.5 mg/l are associated with an increased risk of toxicity. The elimination half-life after oral long term treatment is 50–60 days. Each molecule of amiodarone contains two iodine atoms, approximately 37% of iodine by weight. The most commonly used oral dose of 200 mg per day results in an iodine uptake of 70 mg per day. About 10% (7 mg) is released in the body as iodine, which is an overwhelming amount compared to the normal …

Chest pain is a very common symptom; 20% to 40% of the general population will experience chest pain during their lives,1 and in the UK, up to 1% of visits to a general practitioner are because of chest pain.2 Approximately 700 000 visits (5%) to the emergency department in England and Wales and up to 25% of emergency hospital admissions are because of chest pain.3 There are many causes of chest pain, some of which are benign, while others are potentially life threatening. Importantly, in patients with chest pain caused by an acute coronary syndrome (ACS) or angina, there are effective treatments to improve symptoms and prolong life, emphasising the importance of making timely and accurate diagnoses in patients in whom chest pain may be of cardiac origin. This guideline4 addresses the assessment and diagnosis of patients with recent onset chest pain/discomfort that may be of cardiac origin. Unlike many other National Institute for Health and Clinical Excellence (NICE) clinical guidelines it does not make recommendations for the management of the condition once the diagnosis is made. The NICE unstable angina and NSTEMI clinical guideline5 was published at the same time as the chest pain guideline, and a NICE clinical guideline for the management of angina is currently being prepared.6 The guideline has two separate diagnostic pathways. The first is for patients with acute chest pain who may have an ACS and the second for those with intermittent stable chest pain who may have stable angina. The guideline deals with chest pain of suspected cardiac origin. Thus, for example, the guideline does not apply to patients with pain considered to be caused by recent trauma to the chest. However, many patients presenting with chest pain do not have such clearly apparent alternative explanations and need …

Objective To study trends for 20 years in incidence and 1-year mortality in hospitalised patients who received a diagnosis of either angina or unexplained chest pain (UCP) in Sweden. Design and setting Register study of all patients aged 25–84 years identified from the Swedish National Hospital Discharge Register who were hospitalised with a first-time diagnosis of UCP or angina pectoris during 1987 to 2006. Participants A total of 378 454 patients, 235 855 with UCP and 142 599 with angina. Main outcome measures 1-Year mortality and standardised mortality ratios (SMRs). Results From the period 1987–1991 to 2002–2006, the observed 1-year mortality rate in men and women with UCP aged 25–74 years decreased from 2.19% to 1.45% and from 1.85% to 0.91%, respectively. SMRs decreased from 1.67 (95% CI 1.39 to 1.95) and 1.63 (1.27 to 2.00) to 1.09 (0.96 to 1.23) and 0.88 (0.75 to 1.00). Corresponding decreases in 1-year mortality for a discharge diagnosis of angina were from 6.50% to 2.49% in men and from 4.80% to 1.68% in women, with SMRs decreasing from 2.69 (2.33–3.05) and 2.59 (2.06–3.12) to 1.09 (0.93–1.25) and 1.05 (0.81–1.29), respectively. Similar changes occurred in patients aged 75–84 years. Only men with UCP aged 75–84 years still retained a slightly increased mortality (SMR 1.14 (1.01–1.28)). Conclusions The prognosis of patients admitted with chest pain in which acute myocardial infarction has been ruled out has improved for the past 20 years, such that the 1-year mortality of these patients is now similar to that in the general population.

More than 150 million subjects have diabetes mellitus (DM) worldwide and the number is expected to increase further.w1 Many cases, however, are undiagnosed and do not receive appropriate treatment. The risk of coronary artery disease (CAD) for patients with overt DM is increased by two to three times for men and three to five times for women compared to individuals without DM.1 CAD accounts for 75% of all deaths in DM patients while 30% of patients presenting with acute coronary syndromes have DM.w1 International guidelines consider DM as an equivalent of CAD requiring aggressive anti-atherosclerotic treatment. In the general population, the most typical clinical manifestation of myocardial ischaemia is the occurrence of chest pain. In DM patients, however, myocardial ischaemia is often expressed by angina equivalents: dyspnoea, arrhythmias and (pre-) syncope rather than typical angina. The outcome of CAD events may be three times worse in DM patients who have shortness of breath as a primary symptom. Diabetic patients have a high incidence of occult CAD, reflected by an increased incidence of silent myocardial infarction and ischaemia. The available evidence suggests that occult CAD is a common finding among asymptomatic DM patients, ranging from 20% in healthier subjects to >50% in patients with more complicated DM.w2 This poses the challenge of how to efficiently identify CAD in DM, for diagnosis, referral for invasive coronary angiography, and risk stratification. Various non-invasive methods are available and their diagnostic and prognostic value will be discussed. Although a resting 12 lead ECG should be recorded in every DM patient to detect signs of CAD, one should realise that its diagnostic value is limited for several reasons. The ECG is normal in approximately 50% of patients with CAD and often abnormalities are not sufficiently specific for the diagnosis of CAD. Pathologic …

In patients with acute myocardial infarction, pre-infarction angina is associated with smaller infarct size, probably mainly through myocardial protection induced by ischaemic preconditioning. However, in models of recurrent thrombosis myocardial ischaemia also improves arterial patency. This study investigated whether myocardial ischaemia has any effect on platelet function in patients with coronary artery disease.Twenty patients with low-workload myocardial ischaemia underwent, in a randomised crossover study, two treadmill exercise stress tests (EST) on two separate days: a single maximal EST (EST-1) and a maximal EST (EST-2) performed 45 minutes after a low-workload EST stopped at 1-mm ST depression (p-EST). Platelet reactivity was evaluated by measuring the closure time in response to ADP/collagen by the PFA-100 method, and monocyte-platelet aggregate (MPA) formation and CD41 platelet expression, with and without ADP stimulation, by flow cytometry.Compared to resting values, closure time decreased at peak EST-1 (p0.001) but not at peak EST-2. MPA after ADP stimulation increased more significantly at peak EST-1 compared with peak EST-2 (p0.001). Repetition in seven patients of the pEST/EST-2 protocol after intravenous administration of the adenosine antagonist theophylline showed prevention of the effects of p-EST on exercise-induced platelet reactivity.A short episode of myocardial ischaemia induces protection against an exercise-induced increase of platelet reactivity. These data also suggest a role for adenosine in this phenomenon.

Background: A recent increase in the absolute number of hospitalisations for acute myocardial infarction (AMI) in New Zealand may signal a new epidemic of coronary heart disease (CHD). Objective: To quantify the impact of factors other than incidence of disease on these national hospitalisation trends. Methods: A total of 324 663 electronic records of New Zealand public CHD hospitalisations from 1993 to 2005 were examined. Repeat admissions were identified by record linkage using a unique national health identifier for each patient. Results: Hospitalisations for AMI increased by about 8% a year throughout the 13-year study period. Interhospital transfers increased by 117% over the study period, while readmissions increased by 42%. By 2005 over 60% of all admissions for CHD were readmissions. After accounting for readmissions, hospital transfers and population changes, the age-standardised first AMI hospitalisation rate peaked in 1995 and has since declined by 15%. Reciprocal trends in AMI and angina hospitalisations were seen, indicating changing diagnostic criteria. Overall hospitalisation rates for first CHD events remained relatively steady at about 216.4 events per 100 000 between 1993 and 2000 and subsequently declined by 25% to 162.2 events per 100 000 in 2005. Conclusion: Recent trends in hospitalisation rates for AMI are significantly influenced by factors other than underlying changes in CHD incidence. Increasing absolute numbers of admissions coded as AMI in New Zealand between 1993 and 2005 can be accounted for by increases in readmissions, increases in interhospital transfers, changes in diagnostic criteria for AMI and in demography.

Acute hyperglycaemia has been associated with impaired microvascular function after acute myocardial infarction (AMI), whereas pre-infarction angina (PIA) occurring shortly before the onset of AMI has been shown to reduce microvascular injury after reperfusion.To examine whether acute hyperglycaemia prevents the protective effect of PIA on microvascular function after AMI.We studied 205 patients with a first anterior wall AMI who underwent primary angioplasty within 12 hours of onset. Coronary flow velocity parameters were assessed immediately after reperfusion using a Doppler guidewire. Severe microvascular injury was defined as the presence of systolic flow reversal and diastolic deceleration time600 ms. Echocardiographic wall motion was analysed before revascularisation and 4 weeks later.Acute hyperglycaemia, defined as a blood glucose level ofor=198 mg/dl on admission, was found in 67 (33%) patients. In patients without acute hyperglycaemia, PIA was associated with a lower incidence of systolic flow reversal, a longer diastolic deceleration time and a higher coronary flow reserve. However, in patients with acute hyperglycaemia there was no significant difference in these same parameters between patients with and without PIA. In the presence of acute hyperglycaemia PIA did not improve the change in wall motion score. In a multivariate model, the absence of PIA was an independent determinant of severe microvascular injury in patients without acute hyperglycaemia (odds ratio 6.28, p = 0.001), but not in patients with acute hyperglycaemia.The protective effect of PIA on microvascular function was attenuated in patients with acute hyperglycaemia, resulting in unfavourable functional recovery.

Ischaemic heart disease is becoming an increasingly frequent cause of ischaemic mitral regurgitation (IMR). Three different clinical entities of IMR, which deeply affect the clinical decision making, are distinguishable: the acute IMR complicating an acute myocardial infarction, the true IMR secondary to a transient ischaemic phenomenon, and the chronic functional IMR (FIMR). The incidence of the two first entities is low; the third is much more frequent. IMR can occur acutely in patients sustaining an acute myocardial infarction. The rupture of a papillary muscle—most frequently a head of a posteromedial papillary muscle—is a dramatic mechanical complication of acute myocardial infarction, leading to a very high mortality rate in the absence of immediate surgical intervention. Surgery, most often valve replacement, is warranted after stabilisation of the haemodynamic status using an intra-aortic balloon pump and vasodilators.1 In the absence of such a rupture, the presence of IMR in the acute myocardial infarction phase portends a grave prognosis. Its incidence and clinical importance are largely underestimated, partly because physical examination is rather insensitive. Prompt in-hospital revascularisation can prevent or reverse acute IMR.2 When limited to the inferior wall, early revascularisation may reduce localised left ventricular (LV) remodelling and IMR.3 Early revascularisation also increases survival in patients with acute IMR presenting with shock.4 This second form truly defines IMR because it is secondary to an active ischaemic episode. It is clinically most often revealed by a “whistling angina“ or a “flash pulmonary oedema”.5 It is linked to the presence of a significant stenosis of the right or left circumflex coronary artery. In this situation, the primary treatment is to prevent the episodes of active myocardial ischaemia by a revascularisation procedure. Chronic FIMR, the most common cause of IMR, broadly denotes abnormal function of normal leaflets in the context of …

Background: Evidence suggests that an early interventional strategy for patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) can improve health outcomes but also increase costs when compared with a conservative strategy. Objective: The aim of this study was to assess the cost-effectiveness of an early interventional strategy in different risk groups from a UK health-service perspective. Design: Decision-analytic model based on randomised clinical trial data. Main outcome measures: Costs in UK Sterling at 2003/2004 prices and quality-adjusted life years (QALYs) combined into an incremental cost-effectiveness ratio. Methods: Data from the third Randomised Intervention Trial of unstable Angina (RITA 3) was employed to estimate rates of cardiovascular death and myocardial infarction, costs and health-related quality of life. Cost-effectiveness was estimated over patients’ lifetimes within the decision-analytic model. Results: The mean incremental cost per QALY gained for an early interventional strategy was approximately £55 000, £22 000 and £12 000 for patients at low, intermediate and high risk, respectively. The early interventional strategy is approximately 1%, 35% and 95% likely to be cost-effective for patients at low, intermediate and high risk, respectively, at a threshold of £20 000 per QALY. The cost-effectiveness of early intervention in low-risk patients is sensitive to assumptions about the duration of the treatment effect. Conclusion: An early interventional strategy in patients presenting with NSTE-ACS is likely to be considered cost-effective for patients at high and intermediate risk, but this is less likely to be the case for patients at low risk.

Objective: To describe the investigation and management of patients admitted to hospitals in China with suspected acute coronary syndromes (ACS) and to identify potential areas for improvement in practice. Design: A multicentre prospective survey of sociodemographic characteristics, medical history, clinical features, in-hospital investigations, treatment practices and major events among patients with suspected ACS. Setting: Large urban public hospitals. Patients: Consecutive patients admitted to in-patient facilities with a diagnosis of suspected acute myocardial infarction (MI) or unstable angina pectoris. Main outcome measures: Myocardial infarction/re-infarction, heart failure, death. Results: Between September 2004 and May 2005, data were collected prospectively from 2973 patients admitted to 51 hospitals in 18 provinces of China. An initial diagnosis of ST elevation MI, non-ST elevation MI and unstable angina was made in 43%, 11% and 46% of patients, respectively. Diagnosis was inconsistent with objective measures in up to 20% of cases. At both tertiary and non-tertiary centres, there was little evidence that clinical risk stratification was used to determine the intensity of investigation and management. The mortality rate during hospitalisation was 5% overall and similar in tertiary and non-tertiary centres, but reported in-hospital re-infarction rates (8%) and heart failure rates (16%) were substantially higher at non-tertiary centres. Conclusion: This study has identified a number of areas in the management of ACS patients, including diagnosis and risk stratification, which deviate from current guidelines. These findings will help inform the introduction of widely used quality improvement initiatives such as clinical pathways.

Heart disease is the leading cause of death and morbidity in Western countries, and ischaemic heart disease (IHD) accounts for most cardiac deaths in both sexes.1 This review focuses on gender related issues concerning the epidemiology, pathogenesis, presentation and treatment of IHD. The prevalence and incidence of IHD at all ages tends to be higher in males than in females, increasing with age in both genders (fig 1, table 1).w1 Figure 1 Prevalence of ischaemic heart disease in the USA by age and gender. The prevalence of ischaemic heart disease is lower in women than in men in most classes of age. Reproduced with permission from the Heart Disease and Stroke Statistics—2007 Update. A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee.w1 View this table: Table 1 Age adjusted prevalence and incidence of myocardial infarction (MI) and angina in men and women in the USA However, since the female elderly population is larger than that of males, beyond 75 years of age the absolute number of women discharged for IHD overcomes the number of males (364 000 vs 326 000 per year in the USA).1 At the time of a first coronary event, women are approximately 10 years older than men.2 w2 In the Framingham Heart Study (FHS), angina was the initial diagnosis of IHD in 61% of women but only in 38% of men; in contrast, men more often exhibit myocardial infarction (MI) or sudden death as first manifestations.2 w3 Among patients with suspected acute coronary syndrome (ACS), the discharge diagnosis in women is more commonly unstable angina compared to men.3 4 Over the past three decades, the relative risk (RR) of coronary death has declined similarly in both genders.w4 Thus, in women compared to men the overall prevalence of IHD is lower and the age at presentation is delayed; however, among the elderly, women outnumber men, so that the absolute number of elderly female IHD patients is greater than that of men. In the case–control INTERHEART study of 15152 patients with MI and 14820 controls, 90% of the population attributable risk for MI in both genders was accounted for by the presence of nine modifiable risk factors: raised serum lipoprotein apoB/A1 ratio, smoking, diabetes, psychosocial stress, …

Coronary artery disease is still highly prevalent worldwide, and stable angina pectoris is one of its more common presentations. Stable angina is a clinical expression of myocardial ischaemia associated with fixed atherosclerotic coronary stenosis, which prevents the adaptation of coronary perfusion to an increased oxygen requirement. The goals of treatment include relief of symptoms, inhibition or slowing of disease progression, prevention of future cardiac events such as myocardial infarction (MI), and improved survival. This article reviews the treatment modalities currently available to alleviate the symptoms of chronic angina and to reduce the risk of future MI and cardiac death, including several novel pharmacological treatments, coronary revascularisation, as well as novel technologies that may benefit selected groups of patients who are refractory to both drugs and revascularisation (fig 1⇓). Figure 1 Different modalities of treatment of stable angina. ACE, angiotensin-converting enzyme; CABG, coronary artery bypass grafting; EECP, enhanced external counter pulsation; PCAB, percutaneous in situ coronary artery bypass; PCVA, percutaneous in situ coronary venous arterialisation; PCI, percutaneous coronary intervention; TMR, transmyocardial laser revascularisation. Three major classes of anti-ischaemia drugs are currently used in the medical management of angina pectoris: β-blockers, nitrates (short- and long-acting), and calcium channel antagonists (table 1⇓). All three have been shown to prolong the duration of exercise before the onset of angina and ST segment depression as well as to decrease the frequency of angina. However, none prevents MI or death caused by coronary disease in patients being treated specifically for chronic stable angina. View this table: Table 1 Treatments for stable angina Although the clinical guidelines of the American College of Cardiology/American Heart Association (2002) and the European Society of Cardiology (2006) suggest that β-blockers be used as the first-line agents in patients with stable angina,1–,3 head-to-head comparative trials failed to demonstrate a greater antianginal efficacy for …

Objective We aimed to determine whether cardiothoracic ratio (CTR) within the range conventionally considered normal predicted prognosis in patients undergoing coronary angiography. Design Cohort study with a median of 7 years follow-up. Setting Consecutive patients undergoing coronary angiography at Barts and The London NHS Trust. Subjects 1005 patients with cardiothoracic ratios measured by chest radiography and who subsequently underwent coronary angiography. 7.3% of these patients had a CTR ≥0.5 and were excluded from the analyses. Outcomes All cause mortality and coronary event (non-fatal myocardial infarction or coronary death). Adjustments were made for age, left ventricular dysfunction, ACE inhibitor treatment, body mass index, number of diseased coronary vessels and past coronary artery bypass surgery (CABG). Results The risk of death was increased among patients with a CTR in the upper part of the normal range. 94 (18.9%) of those with a CTR below the median of 0.42 died compared to 120 (27.8%) of those with a CTR between 0.42 and 0.49 (log-rank test p

Previous studies have shown that recent activation of the inflammatory response in coronary atherosclerotic lesions contributes to rapid progressive plaque destabilisation. Neopterin, a by-product of the guanosine triphosphate pathway, is produced by activated macrophages and serves as an activation marker for monocytes/macrophages.To elucidate the role of neopterin in coronary plaque destabilisation by immunohistochemical study of the presence of neopterin in coronary atherectomy specimens obtained from patients with stable angina pectoris (SAP) and unstable angina pectoris (UAP).All patients underwent atherectomy of the primary atherosclerotic lesions responsible for SAP (n = 25) and UAP (n = 25). Frozen samples were studied with antibodies against smooth muscle cells, macrophages, T cells, neutrophils and neopterin.In 22/25 patients with UAP, abundant neopterin-positive macrophages were found at the sites of coronary culprit lesions. However, in 25 lesions from patients with SAP, only 11 lesions showed neopterin positivity. Quantitatively, the neopterin-positive macrophage score was significantly higher (p0.001) in patients with UAP than in patients with SAP. Moreover, the neopterin-positive macrophage score showed a significant positive correlation with the number of neutrophils or T cells, respectively (neutrophils, r = 0.55, p0.001; T cells, r = 0.70, p0.001).Neopterin can be considered as one of the significant factors in the process of plaque inflammation and destabilisation in human coronary atherosclerotic lesions. Its exact role in the process needs to be investigated further.

To examine the long-term cardiovascular consequences of angina in a large epidemiological study.Prospective cohort study conducted between 1972 and 1976 with 20 years of follow-up (the Renfrew-Paisley Study).Renfrew and Paisley, West Scotland, UK.7048 men and 8354 women aged 45-64 years who underwent comprehensive cardiovascular screening at baseline, including the Rose Angina Questionnaire and electrocardiography (ECG).All deaths and hospitalisations for cardiovascular reasons occurring over the subsequent 20 years, according to the baseline Rose angina score and baseline ECG.At baseline, 669 (9.5%) men and 799 (9.6%) women had angina on Rose Angina Questionnaire. All-cause mortality for those with Rose angina was 67.7% in men and 43.3% in women at 20 years compared with 45.4% and 30.4%, respectively, in those without angina (p0.001). Values are expressed as hazards ratio (HR) (95% confidence interval (CI). In a multivariate analysis, men with Rose angina had an increased risk of cardiovascular death or hospitalisation (1.49 (1.33 to 1.66), myocardial infarction (1.63 (1.41 to 1.85)) or heart failure (1.54 (1.13 to 2.10)) compared with men without angina. The corresponding HR (95% CI) for women were 1.38 (1.23 to 1.55), 1.56 (1.31 to 1.85) and 1.92 (1.44 to 2.56). An abnormality on the electrocardiogram (ECG) increased risk further, and both angina and an abnormality on the ECG increased risk most of all compared with those with neither angina nor ischaemic changes on the ECG. Compared with men, women with Rose angina were less likely to have a cardiovascular event (0.54 (0.46 to 0.64)) or myocardial infarction (0.44 (0.35 to 0.56)), although there was no sex difference in the risk of stroke (1.11 (0.75 to 1.65)), atrial fibrillation (0.84 (0.38 to 1.87)) or heart failure (0.79 (0.51 to 1.21)).Angina in middle age substantially increases the risk of death, myocardial infarction, heart failure and other cardiovascular events.