Konstantinos Karatolios

Ruling out coronary artery disease in primary care: development and validation of a simple prediction rule

Background: Chest pain can be caused by various conditions, with life-threatening cardiac disease being of greatest concern. Prediction scores to rule out coronary artery disease have been developed for use in emergency settings. We developed and validated a simple prediction rule for use in primary care. Methods: We conducted a cross-sectional diagnostic study in 74 primary care practices in Germany. Primary care physicians recruited all consecutive patients who presented with chest pain (n = 1249) and recorded symptoms and findings for each patient (derivation cohort). An independent expert panel reviewed follow-up data obtained at six weeks and six months on symptoms, investigations, hospital admissions and medications to determine the presence or absence of coronary artery disease. Adjusted odds ratios of relevant variables were used to develop a prediction rule. We calculated measures of diagnostic accuracy for different cut-off values for the prediction scores using data derived from another prospective primary care study (validation cohort). Results: The prediction rule contained five determinants (age/sex, known vascular disease, patient assumes pain is of cardiac origin, pain is worse during exercise, and pain is not reproducible by palpation), with the score ranging from 0 to 5 points. The area under the curve (receiver operating characteristic curve) was 0.87 (95% confidence interval [CI] 0.83–0.91) for the derivation cohort and 0.90 (95% CI 0.87–0.93) for the validation cohort. The best overall discrimination was with a cut-off value of 3 (positive result 3–5 points; negative result ≤ 2 points), which had a sensitivity of 87.1% (95% CI 79.9%–94.2%) and a specificity of 80.8% (77.6%–83.9%). Interpretation: The prediction rule for coronary artery disease in primary care proved to be robust in the validation cohort. It can help to rule out coronary artery disease in patients presenting with chest pain in primary care.

Chest pain in primary care: Epidemiology and pre-work-up probabilities

Abstract Background/objective: Chest pain is a common complaint and reason for consultation. We aimed to study the epidemiology of chest pain with respect to underlying aetiologies and to establish pre-work-up probabilities for the primary care setting. Methods: We included 1212 consecutive patients with chest pain, aged 35 years and older, attending 74 general practitioners (GPs). GPs recorded symptoms and findings of each patient and provided follow-up information. An independent interdisciplinary reference panel reviewed clinical data of every patient and decided on the aetiology of chest pain at the time of patient recruitment. Results: The prevalence of chest pain among all attending patients was 0.7%. The majority (55.9%) of patients were women. Mean age was 59 (35–93) years. Of these patients, 53.2% had chest pains at the time of consultation and 29.6% presented with acute (<48 hours’ duration) chest pain. Pain originating from the chest wall was diagnosed in 46.6% of all patients, stable ischaemic heart disease (IHD) in 11.1%, and psychogenic disorders in 9.5%; 3.6% had acute coronary syndrome (ACS). Conclusion: The study adds important information about the epidemiology of chest pain as a frequent reason for consulting primary care practitioners. We provide updated pre-work-up probabilities for IHD for each age and sex category.

Impella ventricular support in clinical practice: Collaborative viewpoint from a European expert user group

Mechanical circulatory support represents an evolving field of clinical research and practice. Currently, several cardiac assist devices have been developed but, among different institutions and countries, a large variation in indications for use and device selection exists. The Impella platform is an easy to use percutaneous circulatory support device which is increasingly used worldwide. During 2014, we established a working group of European physicians who have collected considerable experience with the Impella device in recent years. By critically comparing the individual experiences and the operative protocols, this working group attempted to establish the best clinical practice with the technology. The present paper reviews the main theoretical principles of Impella and provides an up-to-date summary of the best practical aspects of device use which may help others gain the maximal advantage with Impella technology in a variety of clinical settings.

In vivo determination of elastic properties of the human aorta based on 4D ultrasound data

Computational analysis of the biomechanics of the vascular system aims at a better understanding of its physiology and pathophysiology. To be of clinical use, however, these models and thus their predictions, have to be patient specific regarding geometry, boundary conditions and material. In this paper we present an approach to determine individual material properties of human aortae based on a new type of in vivo full field displacement data acquired by dimensional time resolved three dimensional ultrasound (4D-US) imaging. We developed a nested iterative Finite Element Updating method to solve two coupled inverse problems: The prestrains that are present in the imaged diastolic configuration of the aortic wall are determined. The solution of this problem is integrated in an iterative method to identify the nonlinear hyperelastic anisotropic material response of the aorta to physiologic deformation states. The method was applied to 4D-US data sets of the abdominal aorta of five healthy volunteers and verified by a numerical experiment. This non-invasive in vivo technique can be regarded as a first step to determine patient individual material properties of the human aorta.

Method for Aortic Wall Strain Measurement With Three-Dimensional Ultrasound Speckle Tracking and Fitted Finite Element Analysis

BACKGROUND Aortic wall strains are indicators of biomechanical changes of the aorta due to aging or progressing pathologies such as aortic aneurysm. We investigated the potential of time-resolved three-dimensional ultrasonography coupled with speckle-tracking algorithms and finite element analysis as a novel method for noninvasive in vivo assessment of aortic wall strain. METHODS Three-dimensional volume datasets of 6 subjects without cardiovascular risk factors and 2 abdominal aortic aneurysms were acquired with a commercial real time three-dimensional echocardiography system. Longitudinal and circumferential strains were computed offline with high spatial resolution using a customized commercial speckle-tracking software and finite element analysis. Indices for spatial heterogeneity and systolic dyssynchrony were determined for healthy abdominal aortas and abdominal aneurysms. RESULTS All examined aortic wall segments exhibited considerable heterogenous in-plane strain distributions. Higher spatial resolution of strain imaging resulted in the detection of significantly higher local peak strains (p ≤ 0.01). In comparison with healthy abdominal aortas, aneurysms showed reduced mean strains and increased spatial heterogeneity and more pronounced temporal dyssynchrony as well as delayed systole. CONCLUSIONS Three-dimensional ultrasound speckle tracking enables the analysis of spatially highly resolved strain fields of the aortic wall and offers the potential to detect local aortic wall motion deformations and abnormalities. These data allow the definition of new indices by which the different biomechanical properties of healthy aortas and aortic aneurysms can be characterized.

Gender differences in presentation and diagnosis of chest pain in primary care.

BackgroundChest pain is a common complaint and reason for consultation in primary care. Research related to gender differences in regard to Coronary Heart Disease (CHD) has been mainly conducted in hospital but not in primary care settings. We aimed to analyse gender differences in aetiology and clinical characteristics of chest pain and to provide gender related symptoms and signs associated with CHD.MethodsWe included 1212 consecutive patients with chest pain aged 35 years and older attending 74 general practitioners (GPs). GPs recorded symptoms and findings of each patient and provided follow up information. An independent interdisciplinary reference panel reviewed clinical data of every patient and decided about the aetiology of chest pain at the time of patient recruitment. Multivariable regression analysis was performed to identify clinical predictors that help to rule in or out CHD in women and men.ResultsWomen showed more psychogenic disorders (women 11,2%, men 7.3%, p = 0.02), men suffered more from CHD (women 13.0%, men 17.2%, p = 0.04), trauma (women 1.8%, men 5.1%, p < 0.001) and pneumonia/pleurisy (women 1.3%, men 3.0%, p = 0.04) Men showed significantly more often chest pain localised on the right side of the chest (women 9.1%, men 25.0%, p = 0.01). For both genders known clinical vascular disease, pain worse with exercise and age were associated positively with CHD. In women pain duration above one hour was associated positively with CHD, while shorter pain durations showed an association with CHD in men. In women negative associations were found for stinging pain and in men for pain depending on inspiration and localised muscle tension.ConclusionsWe found gender differences in regard to aetiology, selected clinical characteristics and association of symptoms and signs with CHD in patients presenting with chest pain in a primary care setting. Further research is necessary to elucidate whether these differences would support recommendations for different diagnostic approaches for CHD according to a patients gender.

Accuracy of symptoms and signs for coronary heart disease assessed in primary care

BACKGROUND Diagnosing the aetiology of chest pain is challenging. There is still a lack of data on the diagnostic accuracy of signs and symptoms for acute coronary events in low-prevalence settings. AIM To evaluate the diagnostic accuracy of symptoms and signs in patients presenting to general practice with chest pain. DESIGN OF STUDY Cross-sectional diagnostic study with delayed-type reference standard. SETTING Seventy-four general practices in Germany. METHOD The study included 1249 consecutive patients presenting with chest pain. Data were reviewed by an independent reference panel, with coronary heart disease (CHD) and an indication for urgent hospital admission as reference conditions. Main outcome measures were sensitivity, specificity, likelihood ratio, predictive value, and odds ratio (OR) for non-trauma patients with a reference diagnosis. RESULTS Several signs and symptoms showed strong associations with CHD, including known vascular disease (OR = 5.13; 95% confidence interval [CI] = 2.83 to 9.30), pain worse on exercise (OR = 4.27; 95% CI = 2.31 to 7.88), patient assumes cardiac origin of pain (OR = 3.20; 95% CI = 1.53 to 6.60), cough present (OR = 0.08; 95% CI = 0.01 to 0.77), and pain reproducible on palpation (OR = 0.27; 95% CI = 0.13 to 0.56). For urgent hospital admission, effective criteria included pain radiating to the left arm (OR = 8.81; 95% CI = 2.58 to 30.05), known clinical vascular disease (OR = 7.50; 95% CI = 2.88 to 19.55), home visit requested (OR = 7.31; 95% CI = 2.27 to 23.57), and known heart failure (OR = 3.53; 95% CI = 1.14 to 10.96). CONCLUSION Although individual criteria were only moderately effective, in combination they can help to decide about further management of patients with chest pain in primary care.

Chest wall syndrome in primary care patients with chest pain: presentation, associated features and diagnosis

BACKGROUND Chest wall syndrome (CWS) is the most frequent aetiology of chest pain in a primary care setting. OBJECTIVE The aims of the study are to describe the epidemiology, clinical characteristics and prognosis of CWS and to provide a simple decision rule for diagnosis. METHODS We included 1212 consecutive patients with chest pain aged 35 years and older attending 74 GPs. GPs recorded symptoms and findings of each patient and provided follow-up information. An independent interdisciplinary reference panel reviewed clinical data of every patient and decided about the aetiology of chest pain at the time of patient recruitment. Multivariable regression analysis was performed to identify clinical predictors that help to rule in or out the diagnosis of CWS. RESULTS GPs diagnosed pain originating from the chest wall in 46.6% of all patients. In most patients, pain was localized retrosternal (52.0%) and/or on the left side (69.2%). In total, 28.0% of CWS patients showed persistent pain and most patients reported no temporal association of pain (72.3%). In total, 55.4% of patients still had chest pain after 6 months. A simple score containing four determinants (localized muscle tension, stinging pain, pain reproducible by palpation and absence of cough) shows an area under the receiver operating characteristic curve of 0.78 (95% confidence interval: 0.75-0.81). CONCLUSIONS This study broadens the knowledge about pain characteristics and the diagnostic accuracy of selected signs and symptoms for CWS. A simple four-point score can help the GP in the diagnostic workup of chest pain patients.

A finite element updating approach for identification of the anisotropic hyperelastic properties of normal and diseased aortic walls from 4D ultrasound strain imaging.

Computational analysis of the biomechanics of the vascular system aims at a better understanding of its physiology and pathophysiology and eventually at diagnostic clinical use. Because of great inter-individual variations, such computational models have to be patient-specific with regard to geometry, material properties and applied loads and boundary conditions. Full-field measurements of heterogeneous displacement or strain fields can be used to improve the reliability of parameter identification based on a reduced number of observed load cases as is usually given in an in vivo setting. Time resolved 3D ultrasound combined with speckle tracking (4D US) is an imaging technique that provides full field information of heterogeneous aortic wall strain distributions in vivo. In a numerical verification experiment, we have shown the feasibility of identifying nonlinear and orthotropic constitutive behaviour based on the observation of just two load cases, even though the load free geometry is unknown, if heterogeneous strain fields are available. Only clinically available 4D US measurements of wall motion and diastolic and systolic blood pressure are required as input for the inverse FE updating approach. Application of the developed inverse approach to 4D US data sets of three aortic wall segments from volunteers of different age and pathology resulted in the reproducible identification of three distinct and (patho-) physiologically reasonable constitutive behaviours. The use of patient-individual material properties in biomechanical modelling of AAAs is a step towards more personalized rupture risk assessment.

Cytokines in Pericardial Effusion of Patients with Inflammatory Pericardial Disease

Background. The role of inflammatory and angiogenic cytokines in patients with inflammatory pericardial effusion still remains uncertain. Methods. We assessed pericardial and serum levels of VEGF, bFGF, IL-1β and TNF-α by ELISA in patients with inflammatory pericardial effusion (PE) of autoreactive (n = 22) and viral (n = 11) origin, and for control in pericardial fluid (PF) and serum (n = 26) of patients with coronary artery disease (CAD) undergoing coronary artery bypass graft surgery. Results. VEGF levels were significantly higher in patients with autoreactive and viral PE than in patients with CAD in both PE (P = 0, 006 for autoreactive and P < 0, 001 for viral PE) and serum (P < 0, 001 for autoreactive and P < 0, 001 for viral PE). Pericardial bFGF levels were higher compared to serum levels in patients with inflammatory PE and patients with CAD (P ≤ 0, 001 for CAD; P ≤ 0, 001 for autoreactive PE; P = 0, 005 for viral PE). Pericardial VEGF levels correlated positively with markers of pericardial inflammation, whereas pericardial bFGF levels showed a negative correlation. IL-1β and TNF-α were detectable only in few PE and serum samples. Conclusions. VEGF and bFGF levels in pericardial effusion are elevated in patients with inflammatory PE. It is thus possible that VEGF and bFGF participate in the pathogenesis of inflammatory pericardial disease.