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Sclerostin, which is primarily produced by the osteocytes, inhibits the canonical Wnt pathway and thereby the osteoblasts and stimulates RANKL release by the osteocytes and thereby osteoclast recruitment. Inhibition of sclerostin therefore causes stimulation of bone formation and inhibition of resorption. In clinical trials, romosozumab, an antibody against sclerostin, increases bone mineral density and reduces the risk of fractures compared with placebo and alendronate. The cardiovascular safety of romosozumab was adjudicated in 2 large clinical osteoporosis trials in postmenopausal women. Compared with placebo, the incidence of cardiovascular events was similar in the 2 treatment groups. Compared with alendronate, the incidence of serious cardiovascular events was higher in women treated with romosozumab. The incidence of serious cardiovascular adverse events was low and post hoc analyses should therefore be interpreted with caution; however, the relative risk seemed unaffected by preexisting cardiovascular disease or risk factors. Sclerostin is expressed in the vasculature, predominantly in vascular smooth muscle cells in the media. However, preclinical and genetic studies have not demonstrated any increased cardiovascular risk with continuously low sclerostin levels or inhibition of sclerostin. Furthermore, no potential mechanisms for such an effect have been identified. In conclusion, while there is no preclinical or genetic evidence of a harmful effect of sclerostin inhibition on cardiovascular safety, the evidence from the large clinical trials in postmenopausal women is conflicting. Romosozumab should therefore be used for the treatment of postmenopausal women with osteoporosis at high risk of fracture after careful consideration of the cardiovascular risk and the balance between benefits and risks., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In patients with angina and nonobstructive coronary artery disease (NOCAD), confirming symptoms due to coronary microvascular dysfunction (CMD) remains challenging. Cardiac magnetic resonance (CMR) assesses myocardial perfusion with high spatial resolution and is widely used for diagnosing obstructive coronary artery disease (CAD)., Objectives: The goal of this study was to validate CMR for diagnosing microvascular angina in patients with NOCAD, compared with patients with obstructive CAD and correlated to the index of microcirculatory resistance (IMR) during invasive coronary angiography., Methods: Fifty patients with angina (65 ± 9 years of age) and 20 age-matched healthy control subjects underwent adenosine stress CMR (1.5- and 3-T) to assess left ventricular function, inducible ischemia (myocardial perfusion reserve index [MPRI]; myocardial blood flow [MBF]), and infarction (late gadolinium enhancement). During subsequent angiography within 7 days, 28 patients had obstructive CAD (fractional flow reserve [FFR] ≤0.8) and 22 patients had NOCAD (FFR >0.8) who underwent 3-vessel IMR measurements., Results: In patients with NOCAD, myocardium with IMR <25 U had normal MPRI (1.9 ± 0.4 vs. controls 2.0 ± 0.3; p = 0.49); myocardium with IMR ≥25 U had significantly impaired MPRI, similar to ischemic myocardium downstream of obstructive CAD (1.2 ± 0.3 vs. 1.2 ± 0.4; p = 0.61). An MPRI of 1.4 accurately detected impaired perfusion related to CMD (IMR ≥25 U; FFR >0.8) (area under the curve: 0.90; specificity: 95%; sensitivity: 89%; p < 0.001). Impaired MPRI in patients with NOCAD was driven by impaired augmentation of MBF during stress, with normal resting MBF. Myocardium with FFR >0.8 and normal IMR (<25 U) still had blunted stress MBF, suggesting mild CMD, which was distinguishable from control subjects by using a stress MBF threshold of 2.3 ml/min/g with 100% positive predictive value., Conclusions: In angina patients with NOCAD, CMR can objectively and noninvasively assess microvascular angina. A CMR-based combined diagnostic pathway for both epicardial and microvascular CAD deserves further clinical validation., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Early risk stratification after primary percutaneous coronary intervention (PPCI) for ST-segment-elevation myocardial infarction is currently challenging. Identification of a low-risk group may improve triage of patients to alternative clinical pathways and support early hospital discharge. Our aim was to assess whether the index of microcirculatory resistance (IMR) at the time of PPCI can identify patients at low risk of early major cardiac complications and to compare its performance against guideline-recommended risk scores., Methods and Results: IMR was measured using a pressure-temperature sensor wire. Cardiac complications were defined as the composite of cardiac death, cardiogenic shock, pulmonary edema, malignant arrhythmias, cardiac rupture, and presence of left ventricular thrombus either before hospital discharge or within 30-day follow-up. In total, 261 patients undergoing PPCI who were eligible for coronary physiology assessment were prospectively enrolled. Twenty-two major cardiac complications were reported. Receiver operating characteristic curve analysis confirmed the utility of IMR in predicting complications and showed significantly better performance than coronary flow reserve, the Primary Angioplasty in Myocardial Infarction II (PAMI-II), and Zwolle score ( P ≤0.006). Low microvascular resistance (IMR ≤40) was measured in 159 patients (61%) of the study population and identified all patients who were free of major cardiac complications (sensitivity: 100%; 95% CI, 80.5-100%)., Conclusions: IMR immediately at the end of PPCI for ST-segment-elevation myocardial infarction reliably predicts early major cardiac complications and performed significantly better than recommended risk scores. These novel data have implications for early risk stratification after PPCI., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objectives: The index of microcirculatory resistance (IMR) provides a reproducible assessment of the status of coronary microvasculature in patients with ST-elevation myocardial infarction (STEMI). Frequency-domain optical coherence tomography (FD-OCT) enables detailed assessment of the morphology of coronary plaque.We sought to determine the influence of the initial culprit coronary plaque anatomy within the infarct-related artery on IMR after stenting in STEMI., Patients and Methods: In 25 STEMI patients IMR was measured immediately before and after stent implantation. FD-OCT imaging was performed at the same time points and atherothrombotic volume (ATV) before stenting, prolapsed+floating ATV after stenting and ΔATV was measured using three different strategies., Results: There were no relationships between preprocedural IMR and FD-OCT parameters. Prestenting IMR was related only to pain to wire time (P: 0.02). Irrespective of the method adopted, the final IMR was related to prestenting ATV (ρ: 0.44, P: 0.03 for method I, ρ: 0.48, P: 0.02 for method II and ρ: 0.30, P: 0.06 for method III) and ΔATV (ρ: 0.41, P: 0.04 for method II and ρ: 0.44, P: 0.03 for method III)., Conclusion: IMR measured before stenting is independent of the appearances of the culprit coronary plaque within the infarct-related artery. IMR after stenting, and more importantly, the change in IMR after stenting, reflect the degree of distal embolization during stent implantation.

Background: Perfusion cardiovascular magnetic resonance (CMR) performed with inadequate adenosine stress leads to false-negative results and suboptimal clinical management. The recently proposed marker of adequate stress, the "splenic switch-off" sign, detects splenic blood flow attenuation during stress perfusion (spleen appears dark), but can only be assessed after gadolinium first-pass, when it is too late to optimize the stress response. Reduction in splenic blood volume during adenosine stress is expected to shorten native splenic T1, which may predict splenic switch-off without the need for gadolinium., Methods: Two-hundred and twelve subjects underwent adenosine stress CMR: 1.5 T (n = 104; 75 patients, 29 healthy controls); 3 T (n = 108; 86 patients, 22 healthy controls). Native T1 spleen was assessed using heart-rate-independent ShMOLLI prototype sequence at rest and during adenosine stress (140 μg/kg/min, 4 min, IV) in 3 short-axis slices (basal, mid-ventricular, apical). This was compared with changes in peak splenic perfusion signal intensity (ΔSI spleen ) and the "splenic switch-off" sign on conventional stress/rest gadolinium perfusion imaging. T1 spleen values were obtained blinded to perfusion ΔSI spleen , both were derived using regions of interest carefully placed to avoid artefacts and partial-volume effects., Results: Normal resting splenic T1 values were 1102 ± 66 ms (1.5 T) and 1352 ± 114 ms (3 T), slightly higher than in patients (1083 ± 59 ms, p = 0.04; 1295 ± 105 ms, p = 0.01, respectively). T1 spleen decreased significantly during adenosine stress (mean ΔT1 spleen  ~ -40 ms), independent of field strength, age, gender, and cardiovascular diseases. While ΔT1 spleen correlated strongly with ΔSI spleen (rho = 0.70, p < 0.0001); neither indices showed significant correlations with conventional hemodynamic markers (rate pressure product) during stress. By ROC analysis, a ΔT1 spleen threshold of ≥ -30 ms during stress predicted the "splenic switch-off" sign (AUC 0.90, p < 0.0001) with sensitivity (90%), specificity (88%), accuracy (90%), PPV (98%), NPV (42%)., Conclusions: Adenosine stress and rest splenic T1-mapping is a novel method for assessing stress responses, independent of conventional hemodynamic parameters. It enables prediction of the visual "splenic switch-off" sign without the need for gadolinium, and correlates well to changes in splenic signal intensity during stress/rest perfusion imaging. ΔT1 spleen holds promise to facilitate optimization of stress responses before gadolinium first-pass perfusion CMR.

Aims: Restoration of effective myocardial reperfusion by primary percutaneous coronary intervention (PPCI) in patients with ST-elevation myocardial infarction is difficult to predict. A method to assess the likelihood of a suboptimal response to conventional pharmacomechanical therapies could be beneficial. We aimed to derive and validate a scoring system that can be used acutely at the time of coronary reopening to predict the likelihood of downstream microvascular impairment in patients with STEMI., Methods and Results: A score estimating the risk of post-procedural microvascular injury defined by an index of microcirculatory resistance (IMR) >40 was initially derived in a cohort of 85 STEMI patients (derivation cohort). This score was then tested and validated in three further cohorts of patients (retrospective [30 patients], prospective [42 patients] and external [29 patients]). The ATI score (age [>50=1]; pre-stenting IMR [>40 and <100=1; ≥100=2]; thrombus score [4=1; 5=3]) was highly predictive of a post-stenting IMR >40 in all four cohorts (AUC: 0.87; p<0.001-derivation cohort, 0.84; p=0.002-retrospective cohort, 0.92; p<0.001-prospective cohort and 0.81; p=0.006-external cohort). In the whole population, an ATI score ≥4 presented a 95.1% risk of final IMR >40, while no cases of final IMR >40 occurred in the presence of an ATI score <2., Conclusions: The ATI score appears to be a promising tool capable of identifying patients during PPCI who are at the highest risk of coronary microvascular impairment following revascularisation. This procedural risk stratification has a number of potential research and clinical applications and warrants further investigation.

Remote ischemic pre-conditioning (rIPC) has emerged as a potential mechanism to reduce ischemia-reperfusion injury. Clinical data, however, have been mixed, and its physiological basis remains unclear, although it appears to involve release of circulating factor(s) and/or neural pathways. Here, the authors demonstrate that adenosine receptor activation is an important step in initiating human pre-conditioning; that pre-conditioning liberates circulating cardioprotective factor(s); and that exogenous adenosine infusion is able to recapitulate release of this factor. However, blockade of adenosine receptors in ischemic tissue does not block the protection afforded by pre-conditioning. These data have important implications for defining the physiology of human pre-conditioning and its translation to future clinical trials.

Aims: Primary percutaneous coronary intervention (PPCI) is the optimal treatment for patients presenting with ST-elevation myocardial infarction (STEMI). An elevated index of microcirculatory resistance (IMR) reflects microvascular function and when measured after PPCI, it can predict an adverse clinical outcome. We measured coronary microvascular function in STEMI patients and compared sequential changes before and after stent implantation., Methods and Results: In 85 STEMI patients, fractional flow reserve, coronary flow reserve, and IMR were measured using a pressure wire (Certus, St Jude Medical, St Paul, MN, USA) immediately before and after stent implantation. Stenting significantly improved all of the measured parameters of coronary physiology including IMR from 67.7 [interquartile range (IQR): 56.2-95.8] to 36.7 (IQR: 22.7-59.5), P < 0.001. However, after stenting, IMR remained elevated (>40) in 28 (32.9%) patients. In 15 of these patients (17.6% of the cohort), only a partial reduction in IMR occurred and these patients were more likely to be late presenters (pain to wire time >6 h). The extent of jeopardized myocardium [standardized beta: -0.26 (IMR unit/Bypass Angioplasty Revascularization Investigation score unit), P: 0.009] and pre-stenting IMR [standardized beta: -0.34 (IMR unit), P: 0.001] predicted a reduction in IMR after stenting (ΔIMR = post-stenting IMR - pre-stenting IMR), whereas thrombotic burden [standardized beta: 0.24 (IMR unit/thrombus score unit), P: 0.01] and deployed stent volume [standardized beta: 0.26 (IMR unit/mm(3) of stent), P: 0.01] were associated with a potentially deleterious increase in IMR., Conclusion: Improved perfusion of the myocardium by stent deployment during PPCI is not universal. The causes of impaired microvascular function at the completion of PPCI treatment are heterogeneous, but can reflect a later clinical presentation and/or the location and extent of the thrombotic burden., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: The aim of this study was to define which measure of microvascular best predicts the extent of left ventricular (LV) infarction., Background: Microvascular injury after ST-segment elevation myocardial infarction (STEMI) is an important determinant of outcome. Several invasive measures of the microcirculation at primary percutaneous coronary intervention (PPCI) have been described. One such measure is zero-flow pressure (Pzf), the calculated pressure at which coronary flow would cease., Methods: In 34 STEMI patients, Pzf, hyperemic microvascular resistance (hMR), and index of microcirculatory resistance (IMR) were derived using thermodilution flow/pressure and Doppler flow/pressure wire assessment of the infarct-related artery following PPCI. The extent of infarction was determined by blinded late gadolinium enhancement on cardiac magnetic resonance at 6 months post-PPCI. Infarction of ≥24% total LV mass was used as a categorical cutoff in receiver-operating characteristic curve analysis., Results: Pzf was superior to both hMR and IMR for predicting ≥24% infarction area under the curve: 0.94 for Pzf versus 0.74 for hMR (p = 0.04) and 0.54 for IMR (p = 0.003). Pzf ≥42 mm Hg was the optimal cutoff value, offering 100% sensitivity and 73% specificity. Patients with Pzf ≥42 mm Hg also had a lower salvage index (61.3 ± 8.1 vs. 44.4 ± 16.8, p = 0.006) and 6-month ejection fraction (62.4 ± 3.6 vs. 49.9 ± 9.6, p = 0.002). In addition, there were significant direct relationships between Pzf and troponin area under the curve (rho = 0.55, p = 0.002), final infarct mass (rho = 0.75, p < 0.0001), percentage of LV infarction and percent transmurality of infarction (rho = 0.77 and 0.74, respectively, p < 0.0001), and inverse relationships with myocardial salvage index (rho = -0.53, p = 0.01) and 6-month ejection fraction (rho = -0.73, p = 0.0001)., Conclusions: Pzf measured at the time of PPCI is a better predictor of the extent of myocardial infarction than hMR or IMR. Pzf may provide important prognostic information at the time of PPCI and merits further investigation in clinical studies with relevant outcome measures., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Monocytes play critical roles in tissue injury and repair following acute myocardial infarction (AMI). Specifically targeting inflammatory monocytes in experimental models leads to reduced infarct size and improved healing. However, data from humans are sparse, and it remains unclear whether monocytes play an equally important role in humans. The aim of this study was to investigate whether the monocyte response following AMI is conserved between humans and mice and interrogate patterns of gene expression to identify regulated functions., Methods and Results: Thirty patients (AMI) and 24 control patients (stable coronary atherosclerosis) were enrolled. Female C57BL/6J mice (n = 6/group) underwent AMI by surgical coronary ligation. Myocardial injury was quantified by magnetic resonance imaging (human) and echocardiography (mice). Peripheral monocytes were isolated at presentation and at 48 h. RNA from separated monocytes was hybridized to Illumina beadchips. Acute myocardial infarction resulted in a significant peripheral monocytosis in both species that positively correlated with the extent of myocardial injury. Analysis of the monocyte transcriptome following AMI demonstrated significant conservation and identified inflammation and mitosis as central processes to this response. These findings were validated in both species., Conclusions: Our findings show that the monocyte transcriptome is conserved between mice and humans following AMI. Patterns of gene expression associated with inflammation and proliferation appear to be switched on prior to their infiltration of injured myocardium suggesting that the specific targeting of inflammatory and proliferative processes in these immune cells in humans are possible therapeutic strategies. Importantly, they could be effective in the hours after AMI., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Rationale: A number of randomized trials are underway, which will address the effects of angiotensin receptor blockers (ARBs) on aortic root enlargement and a range of other end points in patients with Marfan syndrome. If individual participant data from these trials were to be combined, a meta-analysis of the resulting data, totaling approximately 2,300 patients, would allow estimation across a number of trials of the treatment effects both of ARB therapy and of β-blockade. Such an analysis would also allow estimation of treatment effects in particular subgroups of patients on a range of end points of interest and would allow a more powerful estimate of the effects of these treatments on a composite end point of several clinical outcomes than would be available from any individual trial., Design: A prospective, collaborative meta-analysis based on individual patient data from all randomized trials in Marfan syndrome of (i) ARBs versus placebo (or open-label control) and (ii) ARBs versus β-blockers will be performed. A prospective study design, in which the principal hypotheses, trial eligibility criteria, analyses, and methods are specified in advance of the unblinding of the component trials, will help to limit bias owing to data-dependent emphasis on the results of particular trials. The use of individual patient data will allow for analysis of the effects of ARBs in particular patient subgroups and for time-to-event analysis for clinical outcomes. The meta-analysis protocol summarized in this report was written on behalf of the Marfan Treatment Trialists' Collaboration and finalized in late 2012, without foreknowledge of the results of any component trial, and will be made available online (http://www.ctsu.ox.ac.uk/research/meta-trials)., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Invasive assessment of coronary physiology (IACP) offers important prognostic insights in ST-segment elevation myocardial infarction (STEMI) but the dynamics of coronary recovery are poorly understood., Objectives: This study sought to examine the evolution of coronary flow reserve (CFR), index of microcirculatory resistance (IMR), ratio of distal coronary pressure (Pd) to mean aortic pressure (Pa), and fractional flow reserve (FFR) in patients undergoing primary percutaneous coronary intervention (PPCI)., Methods: 82 patients with STEMI underwent IACP at PPCI. Repeat IACP was performed in 61 patients (74%) at day 1 and in 46 patients (56%) at 6 months. Contrast-enhanced cardiac magnetic resonance imaging (CMR) was performed in 45 patients (55%) at day 1 and in 41 patients (50%) at 6 months. Changes in IACP were compared between patients with and without microvascular obstruction (MVO) on CMR., Results: MVO was present in 21 of 45 patients (47%). Patients with MVO had lower CFR at PPCI and day 1 (p < 0.05) and a trend toward higher IMR values (p = 0.07). At 6 months, CFR and IMR were not significantly different between the groups. Baseline flow and Pd/Pa remained stable over time but FFR reduced significantly between PPCI and 6 months (p = 0.008); this reduction was mainly observed in patients with MVO (p = 0.006) but not in those without MVO (p = 0.21)., Conclusions: In PPCI-treated patients with STEMI, coronary microcirculation begins to recover within 24 h and recovery progresses further by 6 months. FFR significantly reduces from baseline to 6 months. The presence of MVO indicates a highly dysfunctional microcirculation., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Predicting the likely success of primary PCI to salvage potential infarcted myocardium is desirable. We compared early invasive parameters of coronary microcirculation function with the levels of circulating endothelin (ET-1) and 6-month ejection fraction after STEMI., Methods and Results: Forty-four STEMI patients underwent assessment of coronary flow reserve (CFR) and index of myocardial resistance (IMR) on completion of PPCI and one day later. Cardiac magnetic resonance (CMR) at 24 h and 6 months assessed ejection fraction, oedema, late gadolinium enhancement, and salvage. In patients with depressed EF, there was no difference in IMR or CFR measured immediately after PPCI compared with those with preserved EF. However, by Day 1, CFR was significantly lower in those with depressed EF [2.0(1.5-2.3) vs. 2.6(2.1-3.3), P = 0.008]. In multivariable models, higher CFR post-PPCI [EST: +8.9 (SE 3.7) per 1 CFR unit, P = 0.03] and greater increase in CFR between post-PPCI and Day 1 [EST: +8.5 (SE 3.4) per 1 CFR unit, P = 0.01] were associated with higher salvage index. Circulating endothelin levels were significantly elevated in the low EF group at both 6 and 24 h, and 24 h levels correlated with CFR., Conclusion: Changes of the coronary microcirculation in the first day after PPCI are associated with 6-month ejection fraction and myocardial salvage. Depressed CFR at 24 h is associated with CMR imaging indices of MVO and haemorrhage and elevated endothelin levels., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013. For permissions please email: journals.permissions@oup.com.)

Objectives: The co-transmitter neuropeptide Y (NPY) is released during high levels of sympathetic stimulation and is a potent vasoconstrictor. We defined the release profile of plasma NPY during acute ST elevation myocardial infarction, and tested the hypothesis that levels correlate with reperfusion measures after treatment with primary percutaneous coronary intervention (PPCI)., Design: Prospective observational study., Setting: University hospital heart centre., Patients: 64 patients (62.6±11.7 years-old, 73% male) presenting throughout the 24-h cycle of clinical activity with ST elevation myocardial infarction., Interventions: PPCI., Main Outcome Measures: NPY was measured (ELISA) in peripheral blood taken before and immediately after PPCI and at 6, 24 and 48 h post-PPCI. Reperfusion was assessed by angiographic criteria, ST segment resolution, invasive measurement of coronary flow reserve and the index of microcirculatory resistance., Results: Plasma NPY levels were highest before PPCI (17.4 (8.8-42.2) pg/ml, median (IQR)) and dropped significantly post-PPCI (12.4 (6.5-26.7) pg/ml, p<0.0001) and after 6 h (9.0 (2.6-21.5) pg/ml, p=0.008). Patients with admission NPY levels above the median were significantly more hypertensive and tachycardic and were more likely to have diabetes mellitus. Patients with angiographic no-reflow (less than thrombolysis in myocardial infarction 3 flow and myocardial blush grade >2, n=16) or no electrocardiographic ST resolution (<70%, n=30) following PPCI had significantly higher plasma NPY levels. Patients with a coronary flow reserve <1.5 or index of microcirculatory resistance >33 also had significantly higher plasma NPY levels pre-PPCI and post-PPCI., Conclusions: Plasma NPY levels correlate with indices of reperfusion and coronary microvascular resistance.

Objectives: To investigate rates of and reasons for second and subsequent stent procedures in an unselected, "real-world" population., Background: Repeat stenting is the primary difference reported in clinical trials of alternative revascularization strategies. The incidence, indication, and outcome for repeat stenting in contemporary practice outside the more selective populations of trials and registries has not been described., Method: All patients undergoing a first percutaneous coronary intervention (PCI) procedure with stenting from January 2001 to August 2009 (10,509) from a large UK tertiary referral and district general hospital were identified. Mortality and the incidence, timing, and indication for repeat revascularization in this population were investigated from patient records., Results: Of 10,509 patients undergoing a first PCI and stent implant 23.5% underwent repeat angiography of which 11.2% required repeat PCI and 2% coronary artery bypass grafting (median follow-up of 3.8 years). A total of 1.3% went on to a third PCI. The commonest indication for repeat stenting was disease progression remote from the original stent (46%) and planned staged PCI (23%); 21% had a stent-related indication. Functional assessment before repeat stenting was used in one-third of stable patients. Mortality was 2.5% per annum., Conclusions: In contemporary practice, patients undergoing a first stenting procedure have a low subsequent mortality, and the substantial majority (86.4%) requires no further revascularization over a median 3.8 year follow-up. For those who do require repeat stenting, this is most commonly at a site remote from the first stent., (Copyright © 2011 Wiley Periodicals, Inc.)

Background: This study evaluates the in-hospital, 30 day and long-term results of stenting for unprotected left main coronary artery disease in our institution., Methods: Between April 2001 and October 2005 all unprotected left main cases were retrospectively reviewed. Outcomes were obtained by case note review and postal questionnaire; primary care physicians were contacted to complete missing data., Results: We identified 100 consecutive patients who underwent unprotected left main procedures, 1.44% of the institution PCI volume. Indications for a percutaneous strategy were non-surgical candidates (47), emergency revascularisation (25) and patient/physician preference (28). Overall procedural success was 97%. The majority of cases (n=78) were performed with a single-stent strategy. 55% received a drug-eluting stent. There were 7 in-hospital deaths, 5 in the emergency group (cardiogenic shock) and 2 non-CABG candidates. Post hospital discharge long-term clinical follow-up was 651+/-431 days (range 6-1741). There were 8 deaths post discharge. Patients presenting as an emergency had a 72% survival rate at long-term follow-up, non-surgical candidates 83%, and patient/physician preference group had a 100% long-term survival. Multivariate analysis revealed cardiogenic shock (HR=7.9, 95% CI 1.7-3.6, p=0.008), failed thrombolysis (HR=8.5, 95% CI 1.7-41.7, p=0.008) and use of a bare-metal stent (HR=4.4, 1.1-17.0, p=0.034) were independent predictors of mortality., Conclusions: Our data suggest that in contemporary practice stenting for unprotected left main disease can be considered as an alternative treatment to surgery for selected patients. The results of randomised controlled trials are awaited.

Background: Anomalous origin of the left circumflex coronary artery from the right sinus of Valsalva or proximal right coronary artery is the most common congenital coronary anatomical abnormality. Whether such vessels are particularly predisposed to atherosclerotic disease in their proximal portion remains controversial. Successful balloon angioplasty has been described, but thus far only six isolated cases of stent deployment in anomalous circumflex vessels have been described in the interventional literature., Methods: Single-center retrospective case study of twenty-two patients with anomalous circumflex coronary arteries. Twelve patients (11/12 male, average age (63 +/- 3) years) underwent successful percutaneous coronary intervention (PCI) with stent deployment in the retroaortic segment of the anomalous vessel., Results: Significant obstructive coronary disease in the retroaortic portion was found in the majority of anomalous left circumflex vessels (16/22, 73%), but did not predict the presence of significant two or three vessel coronary disease (P = 0.14, 0.63). PCI was successful in all cases attempted, with favourable short/medium-term event-free survival., Conclusions: The retroaortic portion of anomalously-arising circumflex coronary arteries is selectively predisposed to atherosclerotic disease. PCI to these vessels is feasible but may be technically challenging.

A 50-year-old man had a large lateral left ventricular wall pseudoaneurysm with rupture after a limited myocardial infarction. This was diagnosed by the combination of flow in and out of the aneurysm and pulsatile flow in the pericardial cavity using color flow and continuous wave Doppler ultrasound. This report describes the case management, the use of echocardiography in this setting, and the implications of pseudoaneurysm formation.

A 64-year-old woman with a mechanical mitral valve prosthesis developed late-onset Candida endocarditis. Blood cultures grew Candida glabrata and Candida krusei. Transesophageal echocardiography demonstrated vegetations on the valve. The patient was not medically fit for valve replacement, but her condition was successfully treated with 6 weeks of intravenous caspofungin therapy.

Background: Bilateral internal thoracic arteries confer improved survival benefit after coronary artery bypass grafting (CABG). Despite increasing evidence, the use of arterial conduits has not been accepted as a primary practice in most of the centres in the UK for various reasons. A series of patients has been analysed to assess the feasibility of total arterial revascularisation as a primary strategy in patients requiring first time CABG., Methods: Altogether 245 patients undergoing first time CABG by one surgeon, from June 1999 to October 2000, were studied. Group 1 consisted of 165 patients undergoing total arterial revascularisation (using bilateral internal thoracic and radial arteries) and group 2 consisted of 80 patients undergoing conventional CABG (using one internal thoracic artery and supplemental veins). Thirty day mortality and early morbidity with particular reference to resternotomy for bleeding, cerebrovascular accidents, renal failure, and sternal dehiscence were the main outcome measures., Results: Patients in group 1 were younger (mean (SD) 60 (10) v 65 (9) years; p<0.001), had lower Parsonnet scores (mean (SD) 5 (5) v 11 (7); p<0.001), and better left ventricular function. Both groups received a similar number of grafts. The percentage of patients undergoing total arterial revascularisation rose from 44% in the first three months to over 75% in the three latter three month periods. Overall 30 day mortality was 1.3%, one patient (0.6%) in group 1 and two patients (2.5%) in group 2. There was a similar incidence of postoperative complications and length of median postoperative stay in both groups., Conclusion: Total arterial revascularisation can be adopted as a primary strategy in most patients undergoing CABG with no increase in mortality or morbidity.

Coronary ischaemia in acute endocarditis is usually due to pre-existing coronary disease or occasionally as a result of embolism from vegetations. A 68 year old man with known mixed aortic valve disease presented with a four week history of progressive exertional angina, which became unstable. He was apyrexial with no peripheral signs of endocarditis. Three sets of blood cultures were negative. Transthoracic echocardiography with suboptimal windows confirmed moderate mixed aortic valve disease. Marked reversible ST segment depression with angina recurred at rest. Aortography showed severe aortic regurgitation with a distorted aortic root. Coronary angiography showed severe proximal narrowing of the left anterior descending and circumflex arteries with an unusual long and tapering contour. Emergency surgery revealed a large anterior aortic root abscess which had destroyed the left and right coronary cusps. Aortic root abscess and other rare causes of extrinsic coronary compression are discussed.

Objective: To assess whether the size of the cytosine-thymine-guanine (CTG) expansion mutation in myotonic dystrophy predicts progression of conduction system disease and cardiac events., Design: Longitudinal study involving ECG and clinical follow up over (mean (SD)) 4.8 (1.8) and 6.2 (1.9) years, respectively, of patients stratified by CTG expansion size (E0 to E4)., Patients: 73 adult patients under annual review in a regional myotonic dystrophy clinic. Patients were grouped into E0/E1 (n = 25), E2 (n = 34), and E3/E4 (n = 14)., Results: The proportion of patients with a QRS complex > 100 ms at baseline increased with the size of the CTG expansion (EO/E1, 4%; E2, 12%; E3/E4, 36%; p = 0.02). This trend was more pronounced at follow up (E0/E1, 4%; E2, 21%; E3/E4, 57%; p = 0.0004). The rate of widening of the QRS complex (ms/year) was similarly related to the size of the mutation (EO/E1, 0.4 (1.3); E2, 1.4 (2.5); E3/E4, 1.5 (1.6); p = 0.04). First degree atrioventricular block was present in 23% of patients at baseline and 34% at follow up, with no significant relation to expansion size. Seven patients suffered a cardiac event during follow up (sudden death in two, permanent pacemaker insertion in three, chronic atrial arrhythmia in two), of whom six were in CTG expansion group E2 or greater. Patients who experienced a cardiac event during follow up had more rapid rates of PR interval increase (9.9 (11.1) v 1.6 (2.9) ms/year; p = 0.008) and a trend to greater QRS complex widening (3.6 (4.5) v 0.9 (1.5) ms/year; p = 0.06) than those who did not., Conclusions: Larger CTG expansions are associated with a higher rate of conduction disease progression and a trend to increased risk of cardiac events in myotonic dystrophy.

Objective: To establish the feasibility and safety of an appropriately trained clinical nurse specialist performing diagnostic cardiac catheterisation., Design: Non-randomised retrospective comparison between the first 100 and second 100 consecutive investigations by a clinical nurse specialist and 200 consecutive patients investigated by two cardiology registrars over a similar period., Setting: Regional cardiac centre performing 3200 catheterisation procedures per annum., Patients: 200 patients undergoing routine (non-emergency) cardiac catheterisation for investigation of ischaemic heart disease., Main Outcome Measures: Procedural complications, image quality, fluoroscopy times., Results: Satisfactory diagnostic images in all nurse specialist cases with no deaths and two complications (coronary artery dissection and femoral pseudoaneurysm). Procedure duration and fluoroscopy times slightly shorter for clinical nurse specialist by 3 and 1.6 minutes, respectively (P < 0.05)., Conclusions: Non-medical practitioners can be trained to perform straightforward cardiac angiography in low risk patients with consultant supervision, as for cardiology registrars. With important restrictions such posts may have a limited role in supporting future consultant based services.

The study set out to assess the incidence and consequences of pericardial and myocardial involvement in seatbelt-related sternal injury. Comparison was made with that from direct sternal trauma and implications for patient management were examined. The study was designed as a prospective sequential single centre study of 60 patients, from a total of 63 consecutive admissions over a 13 month period, admitted with blunt central chest trauma or multiple injuries involving the torso. Clinical status, correlated with echocardiographic, ECG and cardiac enzyme abnormalities were the main outcome measures. The study showed that 25% of 32 patients with seatbelt-related chest injury and 30% of 10 patients with multiple injuries had clinically unsuspected pericardial effusions detected by echocardiography. Pericardial effusion was not associated with an adverse outcome in the seatbelt-related injuries. Abnormalities of ECG or CK-MB isoenzyme levels were non-specific and did not correlate with the presence of pericardial effusion. From these data it is concluded that seatbelt-related sternal trauma is usually relatively benign. Echocardiography detects unsuspected pericardial effusion in a significant minority but ECG and cardiac enzyme estimations are of limited value. The routine admission to hospital of all patients with isolated seatbelt-related sternal trauma for cardiological monitoring is unnecessary. Inpatient treatment should be reserved for patients whose clinical condition, social circumstances or other injuries necessitate admission.

An 18 year old man suddenly lost consciousness while jogging. The ambulance crew documented atypical ventricular tachycardia and an episode of ventricular fibrillation. Coronary angiography showed the left main coronary artery arising from the right sinus of Valsalva. Subsequent surgical coronary revascularisation was successful.

We have evaluated overall and cardiac sympathetic activity in 47 patients undergoing coronary angiography, 27 with stable angina of at least 3 months duration, and 20 with unstable ischaemic symptoms within this period. Cardiac and overall sympathetic activity were assessed using radiotracer noradrenaline kinetic techniques to measure cardiac and total noradrenaline spillover to plasma. Overall sympathetic activity (whole body noradrenaline spillover) was similar in the two groups, whereas cardiac sympathetic activity (cardiac noradrenaline spillover) was strikingly increased in the patients with unstable ischaemic symptoms (102 +/- 23 pmol.min-1 vs 34 +/- 4 pmol.min-1, P < 0.001), as was the cardiac to whole body noradrenaline spillover ratio (0.043 +/- 0.008 vs 0.021 +/- 0.005, P < 0.01). Coronary sinus bloodflow (50 +/- 4 ml.min-1 vs 38 +/- 4 ml.min-1, P < 0.05) and coronary sinus noradrenaline concentration (2.60 +/- 0.38 nmol.l-1 vs 1.41 +/- 0.17 nmol.l-1, P < 0.01) were also increased in the patients with unstable ischemic syndromes. Left ventricular ejection fraction was similar in the two groups (63 +/- 2% vs 62 +/- 2%). Patients with unstable ischaemic symptoms within the previous three months have increased cardiac sympathetic nervous activity compared to patients with stable angina. This may in part explain why patients with unstable ischaemic syndromes are at increased risk of sudden cardiac death.

1. To investigate the effects of acute beta 1-adrenoceptor blockade on sympathetic nervous activity, cardiac and whole-body noradrenaline kinetics were determined during intravenous infusions of saline placebo and of metoprolol (10-15 mg plus 150 micrograms min-1 kg-1) in 10 patients undergoing diagnostic cardiac catheterization, in whom beta-adrenoceptor antagonists had been discontinued for 7 days. 2. Coronary haemodynamics were measured in these 10 patients plus two others. Compared with saline placebo, metoprolol administration was associated with decreases in heart rate (68 +/- 2 to 59 +/- 3 beats/min, P < 0.001) and coronary sinus blood flow (86 +/- 8 to 68 +/- 6 ml/min, P < 0.001) and an increase in calculated coronary vascular resistance (1.42 +/- 0.19 to 1.75 +/- 0.22 mmHg min ml-1, P < 0.001). Arterial and femoral venous noradrenaline concentrations, whole-body noradrenaline clearance and whole-body noradrenaline spillover to arterial plasma did not change. In contrast, cardiac noradrenaline spillover (33.7 +/- 5.1 to 20.2 +/- 4.3 pmol/min, P < 0.05) and cardiac noradrenaline clearance (31 +/- 3 to 23 +/- 3 ml/min, P < 0.001) were significantly decreased during metoprolol administration. 3. These results may be explained by inhibition of pre-junctional facilitatory beta-adrenoceptors, which we hypothesize may be predominantly of the beta 1-subtype in the heart and of the beta 2-subtype in the periphery.

A pregnant 29-year-old woman underwent emergency aortic valve re-replacement for prosthetic valve endocarditis. Cesarean section was performed with the chest open ready for cannulation. Fears of uterine hemorrhage during systemic heparinization for cardiopulmonary bypass were unfounded, and both mother and the 28-week-gestation newborn recovered uneventfully.