Cardiovascular Safety and Sclerostin Inhibition.

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.

Diagnosis of Microvascular Angina Using Cardiac Magnetic Resonance.

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.

Gadolinium-Free Cardiac MR Stress T1-Mapping to Distinguish Epicardial From Microvascular Coronary Disease.

Background: Novel cardiac magnetic resonance (CMR) stress T1 mapping can detect ischemia and myocardial blood volume changes without contrast agents and may be a more comprehensive ischemia biomarker than myocardial blood flow.

Objectives: This study describes the performance of the first prospective validation of stress T1 mapping against invasive coronary measurements for detecting obstructive epicardial coronary artery disease (CAD), defined by fractional flow reserve (FFR <0.8), and coronary microvascular dysfunction, defined by FFR ≥0.

Index of Microcirculatory Resistance at the Time of Primary Percutaneous Coronary Intervention Predicts Early Cardiac Complications: Insights From the OxAMI (Oxford Study in Acute Myocardial Infarction) Cohort.

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.

Splenic T1-mapping: a novel quantitative method for assessing adenosine stress adequacy for cardiovascular magnetic resonance.

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.

The influence of coronary plaque morphology assessed by optical coherence tomography on final microvascular function after stenting in patients with ST-elevation myocardial infarction.

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.

A tool for predicting the outcome of reperfusion in ST-elevation myocardial infarction using age, thrombotic burden and index of microcirculatory resistance (ATI score).

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.

Adenosine Receptor Activation in the "Trigger" Limb of Remote Pre-Conditioning Mediates Human Endothelial Conditioning and Release of Circulating Cardioprotective Factor(s).

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.

Zero-Flow Pressure Measured Immediately After Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction Provides the Best Invasive Index for Predicting the Extent of Myocardial Infarction at 6 Months: An OxAMI Study (Oxford Acute Myocardial Infarction).

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.

How does coronary stent implantation impact on the status of the microcirculation during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction?

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.

Acute myocardial infarction activates distinct inflammation and proliferation pathways in circulating monocytes, prior to recruitment, and identified through conserved transcriptional responses in mice and humans.

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.

Design and rationale of a prospective, collaborative meta-analysis of all randomized controlled trials of angiotensin receptor antagonists in Marfan syndrome, based on individual patient data: A report from the Marfan Treatment Trialists' Collaboration.

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.

Impact of microvascular obstruction on the assessment of coronary flow reserve, index of microcirculatory resistance, and fractional flow reserve after ST-segment elevation myocardial infarction.

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.

Early change in invasive measures of microvascular function can predict myocardial recovery following PCI for ST-elevation myocardial infarction.

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.

Relationship of plasma neuropeptide Y with angiographic, electrocardiographic and coronary physiology indices of reperfusion during ST elevation myocardial infarction.

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.

Repeat percutaneous coronary revascularization: indications and outcomes in a "real world" cohort.

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.

Long-term outcomes of percutaneous coronary intervention for unprotected left main coronary artery disease.

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.

Percutaneous coronary intervention with stent deployment in anomalously-arising left circumflex coronary arteries.

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.

Left ventricular pseudoaneurysm and rupture after limited myocardial infarction.

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.

Candida prosthetic valve endocarditis cured by caspofungin therapy without valve replacement.

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.

Total arterial revascularisation as a primary strategy for coronary artery bypass grafting.

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.