D Kilpatrick

Source of Electrocardiographic ST Changes in Subendocardial Ischemia

To clarify the source of electrocardiographic ST depression associated with ischemia, a sheep model of subendocardial ischemia was developed in which simultaneous epicardial and endocardial ST potentials were mapped, and a computer model using the bidomain technique was developed to explain the results. To produce ischemia in different territories of the myocardium in the same animal, the left anterior descending coronary artery and left circumflex coronary artery were partially constricted in sequence. Results from 36 sheep and the computer simulation are reported. The distributions of epicardial potentials from either ischemic source were very similar (r=0.77+/-0.14, P<0.0001), with both showing ST depression on the free wall of the left ventricle and no association between the ST depression and the ischemic region. However, endocardial potentials showed that ST elevation was directly associated with the region of reduced blood flow. Insulating the heart from the surrounding tissue with plastic increased the magnitude of epicardial ST potentials, which was consistent with an intramyocardial source. Increasing the percent stenosis of a coronary artery increased epicardial ST depression at the lateral boundary and resulted in ST elevation starting from the ischemic center as ischemia became transmural. Computer simulation using the bidomain model reproduced the epicardial ST patterns and suggested that the ST depression was generated at the lateral boundary between ischemic and normal territories. ST depression on the epicardium reflected the position of this lateral boundary. The boundaries of ischemic territories are shared, and only those appearing on the free wall contribute to external ST potential fields. These effects explain why body surface ST depression does not localize cardiac ischemia in humans.

The effect of conductivity values on ST segment shift in subendocardial ischaemia

The aim of this study was to investigate the effect of different conductivity values on epicardial surface potential distributions on a slab of cardiac tissue. The study was motivated by the large variation in published bidomain conductivity parameters available in the literature. Simulations presented are based on a previously published bidomain model and solution technique which includes fiber rotation. Three sets of conductivity parameters are considered and an alternative set of nondimensional parameters relating the tissue conductivities to blood conductivity is introduced. These nondimensional parameters are then used to study the relative effect of blood conductivity on the epicardial potential distributions. Each set of conductivity parameters gives rise to a distinct set of epicardial potential distributions, both in terms of morphology and magnitude. Unfortunately, the differences between the potential distributions cannot be explained by simple combinations of the conductivity values or the resulting dimensionless parameters.

The impact of focused transthoracic echocardiography in the pre‐operative clinic

Patients with suspected or symptomatic cardiac disease, associated with increased peri‐operative risk, are often seen by anaesthetists in the pre‐assessment clinic. The use of transthoracic echocardiography in this setting has not been reported. This prospective observational study investigated the effect of echocardiography on the anaesthetic management plan in 100 patients who were older than 65 years or had suspected cardiac disease. Echocardiography was performed by an anaesthetist, and was validated by a cardiologist. Overall, the anaesthetic plan was changed in 54 patients. Haemodynamically significant cardiac disease was revealed in 31 patients, resulting in a step‐up of treatment in 20 patients, including: cardiology referral (four patients); altered surgical (two) and anaesthetic (four) technique; use of invasive monitoring (13); planned use of vasopressor infusion (10); and postoperative high dependency care (five). Reassuring negative findings in 69 patients led to a step‐down in treatment in 34 patients: altered anaesthetic technique (six); procedure not cancelled (10); cardiology referral not made (10); use of invasive monitoring not required (seven); and high dependency care not booked (11). We conclude that focused transthoracic echocardiography in the pre‐operative clinic is feasible and frequently alters management in patients with suspected cardiac disease.

The impact of pre-operative focused transthoracic echocardiography in emergency non-cardiac surgery patients with known or risk of cardiac disease

This prospective observational study investigated the effect of focused transthoracic echocardiography in 99 patients who had suspected cardiac disease or were ≥ 65 years old, and were scheduled for emergency non‐cardiac surgery. The treating anaesthetist completed a diagnosis and management plan before and after transthoracic echocardiography, which was performed by an independent operator. Clinical examination rated cardiac disease present in 75%; the remainder were asymptomatic. The cardiac diagnosis was changed in 67% and the management plan in 44% of patients after echocardiography. Cardiac disease was identified by echocardiography in 64% of patients, which led to a step‐up of treatment in 36% (4% delay for cardiology referral, 2% altered surgery, 4% intensive care and 26% intra‐operative haemodynamic management changes). Absence of cardiac disease in 36% resulted in a step‐down of treatment in 8% (no referral 3%, intensive care 1% or haemodynamic treatment 4%). Pre‐operative focused transthoracic echocardiography in patients admitted for emergency surgery and with known cardiac disease or suspected to be at risk of cardiac disease frequently alters diagnosis and management.

The impact on cardiac diagnosis and mortality of focused transthoracic echocardiography in hip fracture surgery patients with increased risk of cardiac disease: a retrospective cohort study

Hip fracture surgery is associated with a high rate of mortality and morbidity; heart disease is the leading cause and is often unrecognised and inadequately treated. Pre‐operative focused transthoracic echocardiography by anaesthetists frequently influences management, but mortality outcome studies have not been performed to date. Mortality over the 12 months after hip fracture surgery, in 64 patients at risk of cardiac disease who received pre‐operative echocardiography, was compared with 66 randomised historical controls who did not receive echocardiography. Mortality was lower in the group that received echocardiography over the 30 days (4.7% vs 15.2%, log rank p = 0.047) and 12 months after surgery (17.1% vs 33.3%, log rank p = 0.031). Hazard of death was also reduced with pre‐operative echocardiography over 12 months after adjustment for known risk factors (hazard ratio 0.41, 95% CI 0.2–0.85, p = 0.016). Pre‐operative echocardiography was not associated with a delay in surgery. These data support a randomised controlled trial to confirm these findings.

The importance of anisotropy in modeling ST segment shift in subendocardial ischaemia

In this paper, a simple mathematical model of a slab of cardiac tissue is presented in an attempt to better understand the relationship between subendocardial ischaemia and the resulting epicardial potential distributions. The cardiac tissue is represented by the bidomain model where tissue anisotropy and fiber rotation have been incorporated with a view to predicting the epicardial surface potential distribution. The source of electric potential in this steady-state problem is the difference between plateau potentials in normal and ischaemic tissue, where it is assumed that ischaemic tissue has a lower plateau potential. Simulations with tissue anisotropy and no fiber rotation are also considered. Simulations are performed for various thicknesses of the transition region between normal and ischaemic tissue and for various sizes of the ischaemic region. The simulated epicardial potential distributions, based on an anisotropic model of the cardiac tissue, show that there are large, potential gradients above the border of the ischaemic region and that there are dips in the potential distribution above the region of ischaemia. It could be concluded from the simulations that it would be possible to predict the region of subendocardial ischaemia from the epicardial potential distribution, a conclusion contrary to observed experimental data. Possible reasons for this discrepancy are discussed. In the interests of mathematical simplicity, isotropic models of the cardiac tissue are also considered, but results from these simulations predict epicardial potential distributions vastly different from experimental observations. A major conclusion from this work is that tissue anisotropy and fiber rotation must be included to obtain meaningful and realistic epicardial potential distributions.

MATHEMATICAL MODELLING OF FLOW THROUGH AN IRREGULAR ARTERIAL STENOSIS

A mathematical model of flow through an irregular arterial stenosis is developed. The model is two-dimensional and axi-symmetric with the stenosis outline obtained from a three-dimensional casting of a mildly stenosed artery. Agreement between modelled and experimental pressure drops (obtained from an axi-symmetric machined stenosis with the same profile) is excellent. Results are also obtained for a smooth stenosis model, similar to that used for most mathematical modelling studies. This model overestimates the pressure drop across the stenosis, as well as the wall shear stress and separation Reynolds number. Also, the smooth model predicts one instead of three recirculation zones present in the irregular model. The original stenosis is modified to increase the severity from 48 and 87% areal occlusion, while maintaining the same general shape. This has the effect of increasing the pressure drop by an order of magnitude and decreasing the number of recirculation zones to one, with a lower separation Reynolds number.

Forward and inverse electrocardiographic calculations using resistor network models of the human torso.

An automated method of modelling the electrical properties of the human thorax from horizontal section data such as computerized tomographic scans has been used to develop both forward and inverse transformations between epicardial and body surface potential distributions. Eleven torso models with varying geometry and organ configurations have been studied. For the forward calculations, a standard dipole-like source is placed along the axis of the heart. Inverse calculations are performed using a measured body surface potential distribution and are based on a division of the surface of the heart into 25 source regions, producing epicardial potentials on these regions. A regularization method is used to stabilize the inverse solutions. Both forward and inverse solutions show substantial differences between models. These findings imply that matching models with patient geometry may be necessary in order to use such solutions in a clinical setting.

Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open-label, randomised, long-term extension trial

BACKGROUND Pulmonary arterial hypertension is a chronic disease associated with poor long-term outcomes. Identifying predictors of long-term outcome in pulmonary arterial hypertension is important to assess disease severity and guide treatment. We investigate associations between efficacy parameters and long-term outcomes in patients with pulmonary arterial hypertension receiving riociguat in the PATENT-2 study. We also present safety and efficacy data from the final data cutoff of PATENT-2, where most patients had received at least 2 years of riociguat treatment. METHODS Eligible patients from the PATENT-1 study entered the PATENT-2 open-label extension, which will continue until all patients transition to the commercial drug. All patients received riociguat individually adjusted to a maximum dose of 2·5 mg three times a day. The primary endpoint was safety and tolerability, assessed with recording adverse events, serious adverse events, discontinuations, and deaths; exploratory assessments included 6-min walking distance (6MWD), WHO functional class, N-terminal prohormone of brain natriuretic peptide (NT-proBNP)concentrations, Borg dyspnoea score, health-related quality of life (EQ-5D score), survival, and clinical worsening-free survival. Association between efficacy parameters and long-term outcomes was assessed using Kaplan-Meier analyses and a Cox proportional-hazards regression model. PATENT-2 is registered at ClinicalTrials.gov, number NCT00863681. FINDINGS 396 patients entered PATENT-2, of whom 197 patients were receiving riociguat monotherapy and 199 were receiving riociguat in combination with endothelin receptor antagonists or prostanoids, or both. A significant association was noted between 6MWD, NT-proBNP concentration, and WHO functional class and overall survival at baseline (p=0·0006, 0·0225, and 0·0191, respectively), and at follow-up (p=0·021, 0·0056, and 0·0048, respectively). Riociguat was well tolerated in PATENT-2. Serious adverse events were recorded in 238 (60%) of the total population, and 45 (11%) patients discontinued treatment because of an adverse event. Improvements in 6MWD, WHO functional class, and NT-proBNP concentrations were maintained after 2 years of treatment. INTERPRETATION These results support the long-term use of riociguat in patients with pulmonary arterial hypertension, and emphasise the prognostic value of 6MWD, WHO functional class, and NT-proBNP concentrations. FUNDING Bayer Pharma AG.

Correlation Between Functional and Electrophysiological Recovery in Acute Ischemic Stroke

BACKGROUND AND PURPOSE There is still controversy about the prognostic value of motor evoked potentials (MEPs) in the assessment of hemiplegia. The aims of this study are to determine the relationship between functional and electrophysiological recovery and thus the value of MEP as a prognostic indicator of clinical outcome in acute ischemic stroke. METHODS Seventeen healthy subjects and 38 stroke patients were included in this study. Functional recovery was assessed with the Modified Canadian Neurological Scale (MCNS), the Barthel Activities of Daily Living Index (BI), and the Rankin scale. Transcranial magnetic stimulation was used to determine the change in central motor conduction time (CMCT). Stroke outcome was assessed at the end of 2 weeks. One-way ANOVA with post hoc comparisons using the Scheffé procedure as well as t tests were used to assess the significance of the results in this study. RESULTS Unpaired t test showed significantly higher mean scores of the MCNS (2P=0.001), BI (2P=0.002), and Rankin scale (P<0.001) at day 14 in the group of patients with recordable MEP at day 1. A better clinical improvement with a higher mean score of the MCNS (2P<0.001), BI (2P<0.001), and the Rankin scale (2P<0.001) was also observed in the patients in whom the CMCT improved. CONCLUSIONS These data show that there is a close relationship between clinical and electrophysiological improvement and that MEP is a useful prognostic indicator of clinical outcome.