Flemish network on rare connective tissue diseases (CTD): patient pathways in systemic sclerosis. First steps taken.

Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.

Statins and psoriasis: Position statement by the Psoriasis Task Force of the European Academy of Dermatology and Venerology.

BACKGROUND: Psoriasis is associated with an increased mortality risk, with cardiovascular disease being the leading excess cause (in a dose-response manner with psoriasis severity). Statins have demonstrated a reduction in all-cause mortality with no excess of adverse events among the general population. The underuse of interventions in cardiovascular prevention, such as statins, for patients with psoriasis may be the result of an insufficient evaluation. OBJECTIVES: To provide the dermatologist with a tool for systematizing the treatment of dyslipidemia in psoriasis, which generally escapes the scope of dermatological practice, and to facilitate decision-making about the referral and treatment of patients. METHODS: The Psoriasis Task Force of the European Academy of Dermatology and Venereology performed this two-phase study to achieve a consensus and create recommendations on the use of statin therapy in patients with psoriasis. The first phase included a systematic review to identify a list of outline concepts and recommendations according to guidelines. The second phase consisted in a two-round Delphi study to evaluate those recommendations not literally taken from guidelines. RESULTS: A list of 47 concepts and recommendations to be followed by dermatologists involved in the treatment of patients with moderate-severe psoriasis was created. It included six main concepts about cardiovascular risk and psoriasis, six items related with the role of low-density lipoprotein cholesterol (LDL-c) and the benefits of statin treatment in psoriasis patients, eight recommendations about how cardiovascular risk should be assessed, three on the role of non-invasive cardiovascular imaging, three on LDL-c thresholds, eight key points related to statin prescription, 10 on statin treatment follow-up and three on patient referral to another specialist. CONCLUSIONS: The application of this position statement (close final list of concepts and recommendations) will help dermatologists to manage dyslipidemia and help psoriasis patients to reduce their cardiovascular risk.

Effect of supplementing rumen-protected methionine, lysine, and histidine to low-protein diets on the performance and nitrogen balance of dairy cows.

Lowering the dietary protein content can reduce N excretions and NH3 emissions from manure and increase milk N efficiency of dairy cows. However, milk yield (MY) and composition can be compromised due to AA deficiency. Methionine and Lys are known as first limiting EAA for dairy cows, and recently His is also mentioned as limiting, especially in grass-based or low-protein diets. To examine this, a trial was conducted with a 3-wk pre-experimental adaptation period (diet 16.5% crude protein), followed by a depletion period of 4 wk, in which 39 cows (average ± standard deviation: 116 ± 29.3 d in milk, 1.8 ± 1.2 lactations, 638 ± 73.2 kg of body weight, and 32.7 ± 5.75 kg MY/d) received a low-protein diet (CTRL) (14.5% crude protein). Then, taking into account parity, His plasma concentration, and MY, cows were randomly assigned to 1 of 3 treatment groups during the rumen-protected (RP) AA period of 7 wk; (1) CTRL; (2) CTRL + RP-Met + RP-Lys (MetLys); (3) CTRL + RP-Met + RP-Lys + RP-His (MetLysHis). Products were dosed, assuming requirements for digestible (d) Met, dLys, and dHis being, respectively, 2.4%, 7.0%, and 2.4% of intestinal digestible protein. In the cross-back period of 5 wk, all cows received the CTRL diet. During the last week of each period, a N balance was conducted by collecting total urine and spot samples of feces. Total feces production was calculated using the inert marker TiO2. Statistical analysis was performed with a linear mixed model with cow as random effect and data of the last week of the pre-experimental period used as covariate for the animal performance variables. No effect of supplementing RP-Met and RP-Lys nor RP-Met, RP-Lys, and RP-His on feed intake, milk performance, or milk N efficiency was observed. However, the plasma AA profile indicated additional supply of dMet, dLys, and dHis. Nevertheless, evaluation of the AA uptake relative to the cow's requirements showed that most EAA (exclusive Arg and Thr) were limiting over the whole experiment. Only dHis was sufficiently supplemented during the RP-AA period due to an overestimation of the diet's dMet and dLys supply in the beginning of the trial. The numerically increased milk urea N and urinary N excretion when RP-Met, RP-Lys, and RP-His were added to the low-protein diet suggest an increased catabolism of the excess His.

Importance of characteristics and modalities of physical activity and exercise in defining the benefits to cardiovascular health within the general population: recommendations from the EACPR (Part I).

Over the last decades, more and more evidence is accumulated that physical activity (PA) and exercise interventions are essential components in primary and secondary prevention for cardiovascular disease. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit in achieving cardiovascular health. The present paper, as the first of a series of three, will make specific recommendations on the importance of these characteristics for cardiovascular health in the population at large. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and the individual member of the public. Based on previous and the current literature, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and exercise.

Importance of characteristics and modalities of physical activity and exercise in the management of cardiovascular health in individuals with cardiovascular risk factors: recommendations from the EACPR. Part II.

In a previous paper, as the first of a series of three on the importance of characteristics and modalities of physical activity (PA) and exercise in the management of cardiovascular health within the general population, we concluded that, in the population at large, PA and aerobic exercise capacity clearly are inversely associated with increased cardiovascular disease risk and all-cause and cardiovascular mortality and that a dose­response curve on cardiovascular outcome has been demonstrated in most studies. More and more evidence is accumulated that engaging in regular PA and exercise interventions are essential components for reducing the severity of cardiovascular risk factors, such as obesity and abdominal fat, high BP, metabolic risk factors, and systemic inflammation. However, it is less clear whether and which type of PA and exercise intervention (aerobic exercise, dynamic resistive exercise, or both) or characteristic of exercise (frequency, intensity, time or duration, and volume) would yield more benefit for each separate risk factor. The present paper, therefore, will review and make recommendations for PA and exercise training in the management of cardiovascular health in individuals with cardiovascular risk factors. The guidance offered in this series of papers is aimed at medical doctors, health practitioners, kinesiologists, physiotherapists and exercise physiologists, politicians, public health policy makers, and individual members of the public. Based on previous and the current literature overviews, recommendations from the European Association on Cardiovascular Prevention and Rehabilitation are formulated regarding type, volume, and intensity of PA and regarding appropriate risk evaluation during exercise in individuals with cardiovascular risk factors.

[Population-level changes to promote cardiovascular health]. / Zmeny na úrovni populace zamerené na podporu kardiovaskulárního zdraví

BACKGROUND: Cardiovascular diseases (CVD) cause 1.8 million premature (<75 years) death annually in Europe. The majority of these deaths are preventable with the most efficient and cost-effective approach being on the population level. The aim of this position paper is to assist authorities in selecting the most adequate management strategies to prevent CVD. DESIGN AND METHODS: Experts reviewed and summarized the published evidence on the major modifiable CVD risk factors: food, physical inactivity, smoking, and alcohol. Population-based preventive strategies focus on fiscal measures (e.g. taxation), national and regional policies (e.g. smoke-free legislation), and environmental changes (e.g. availability of alcohol). RESULTS: Food is a complex area, but several strategies can be effective in increasing fruit and vegetables and lowering intake of salt, saturated fat, trans-fats, and free sugars. Tobacco and alcohol can be regulated mainly by fiscal measures and national policies, but local availability also plays a role. Changes in national policies and the built environment will integrate physical activity into daily life. CONCLUSION: Societal changes and commercial influences have led to the present unhealthy environment, in which default option in life style increases CVD risk. A challenge for both central and local authorities is, therefore, to ensure healthier defaults. This position paper summarizes the evidence and recommends a number of structural strategies at international, national, and regional levels that in combination can substantially reduce CVD.

Cardiovascular determinants and prognostic significance of CC Chemokine Ligand-18 (CCL18/PARC) in patients with stable coronary artery disease.

Chemokines are important mediators of angiogenesis, hematopoiesis and leucocyte trafficking. CC Chemokine Ligand-18 (CCL18)/ pulmonary and activation-regulated chemokine (PARC) is a circulating chemokine that plays a role in injury healing, physiological homing of mononuclear blood cells and inflammatory responses. CCL18/PARC is also expressed in atherosclerotic plaques. We prospectively evaluated CCL18/PARC levels and their cardiovascular and biological determinants in a large cohort of 285 patients with stable coronary heart disease who were subsequently followed for 3 years for hard cardiac events. It was found that CCL18/PARC levels were associated with decreased cardiac function, decreased exercise capacity and increased inflammatory parameters including interleukin-6 (IL-6) and hs-CRP. More importantly high CCL18/PARC levels were an independent predictor of future cardiovascular events. Therefore, CCL18/PARC is a potential diagnostic and prognostic parameter in patients with stable coronary artery disease.

Dilated cardiomyopathy caused by a novel TNNT2 mutation-added value of genetic testing in the correct identification of affected subjects.

Diagnosing familial dilated cardiomyopathy requires careful family history taking and clinical evaluation in first degree relatives. Based on the results of these findings the diagnosis may be established in the proband. However, due to the age-dependent expression of the disease, doubt may persist regarding the exact status of other family members, especially in young individuals. Here we present a family with DCM in whom we identified an underlying cardiac troponin T (TNNT2) mutation. Genetic testing was essential for the detection of asymptomatic carriers as well as for exclusion of the disease in other family members.

[Guidelines on cardiovascular disease prevention in clinical practice. Belgian Working Group on Cardiovascular Prevention and Rehabilitation]. / Recommandations relatives a la prévention des maladies cardiovasculaires en pratique clinique. Groupe de travail belge de prévention des maladies cardiovasculaires.

Since more than 15 years, expert groups and various European Scientific Societies have written Guidelines on Cardiovascular Disease Prevention. Because of the rapid evolution of science, it is necessary to adapt regularly these guidelines. The last version dates from 2007 and has been written by the " Fourth Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice ". In this issue, the more recent Guidelines are summarised and we focus on highlighting the aspects of these Guidelines that have changed since the previous version published in this journal in 2005.

Technological advances in tissue Doppler imaging echocardiography.

Tissue Doppler imaging is a recently introduced echocardiographic tool for measuring myocardial velocities. In this article the physical principles and different myocardial velocity imaging modalities are discussed. Examples of practical applications and clinical use of this non-invasive imaging technique are provided.

Triplane tissue Doppler imaging: a novel three-dimensional imaging modality that predicts reverse left ventricular remodelling after cardiac resynchronisation therapy.

BACKGROUND: Several two-dimensional (2-D) tissue Doppler imaging (TDI) echocardiographic techniques have proved useful to identify responders to cardiac resynchronisation therapy (CRT). Recently a 3-D probe allowing simultaneous acquisition of TDI data in three imaging planes became available. OBJECTIVE: To evaluate the value of triplane TDI to predict reverse left ventricular (LV) remodelling after CRT. METHODS: Sixty patients with heart failure, scheduled for CRT, underwent triplane echocardiography with simultaneous TDI acquisition before and 6 months after implantation. From the triplane dataset a 3-D LV volume was generated and LV volumes and ejection fraction were calculated. Intraventricular dyssynchrony was quantitatively analysed by evaluating time from onset of the QRS complex to peak myocardial systolic velocity in 12 LV segments from the triplane dataset and calculation of the standard deviation (Ts-SD-12). Clinical response was defined as an improvement of at least one New York Heart Association class. Reverse LV remodelling was defined as >/=15% decrease of LV end-systolic volume at 6 months' follow-up. RESULTS: Responders to CRT had significantly more LV dyssynchrony at baseline than non-responders (mean (SD) Ts-SD-12: 42 (14) vs 22 (12), p<0.001). A cut-off value of 33 ms for baseline Ts-SD-12, acquired from the triplane TDI dataset, yielded a sensitivity of 89% with a specificity of 82% to predict clinical response to CRT; sensitivity and specificity to predict reverse LV remodelling were 90% and 83%, respectively. CONCLUSION: Triplane TDI echocardiography predicts clinical response and reverse LV remodelling 6 months after CRT implantation.

Poststress left ventricular ejection fraction is an independent predictor of major cardiac events in patients with coronary artery disease and impaired left ventricular function.

AIM: The aim of this study was to investigate the prognostic value of myocardial perfusion and function SPECT imaging in patients with coronary artery disease (CAD) and poor left ventricular (LV) function. METHODS: We studied 261 patients (231 men, age 66+/-10 years) with CAD and a resting LV ejection fraction (LVEF)

Aortic reflection coefficients and their association with global indexes of wave reflection in healthy controls and patients with Marfan's syndrome.

Early return of reflected pressure waves increases the load on central arteries and may increase the risk of aortic rupture in patients with Marfan's syndrome (MFS). To assess whether wave reflection is elevated in MFS, we used ultrasound and MRI to measure central pressure and flow waveforms in 26 patients (13-54 yr of age) and 26 age- and gender-matched controls. Aortic systolic and diastolic cross-sectional areas were measured at the ascending and descending aorta (AA and DA), diaphragm (DIA), and lower abdominal aorta (AB). From these measurements, local characteristic impedance (Z(0-xx)) and local reflection coefficients (Gamma(xx-yy)) were calculated. Calculated global wave reflection indexes were the augmentation index (AIx) and the ratio of backward to forward pressure wave (P(b)/P(f)). The aorta was wider in MFS patients at AA (P < 0.01) and DA (P < 0.01). Aortic pulse wave velocity was 42 cm/s higher in MFS patients (P < 0.05). Z(0-xx) was not different between groups, except at DA, where it was lower in MFS patients. In controls, Gamma(AA-DA) was 0.31 +/- 0.08, Gamma(DA-DIA) was 0.00 +/- 0.11, and Gamma(DIA-AB) was 0.31 +/- 0.16. Mean values of Gamma(xx-yy) were not different between MFS patients and controls. In controls, aging diminished Gamma(AA-DA) but increased Gamma(DIA-AB). Clear age-related patterns were absent in MFS patients. AIx or P(b)/P(f) was not higher in MFS patients than in controls. There were indications for enhanced wave reflection in young MFS patients. Our data demonstrated that the major determinants of AIx were pulse wave velocity and the effective length of the arterial system and, to a lesser degree, HR and P(b)/P(f).

Coronary risk factors and inflammation in patients with coronary artery disease and internal cardioverter defibrillator implants.

BACKGROUND: The internal cardioverter defibrillator (ICD) is increasingly used to treat ventricular tachyarrhythmias in patients with coronary artery disease (CAD). The burden of coronary risk factors and inflammation is however not well studied in these high risk patients. STUDY AIMS: The aim of the present study was to describe the prevalence of coronary risk factors (including lipid values) and inflammation (including high sensitive-C-reactive protein, hs-CRP) in patients with CAD and ICD implants. METHODS: Baseline clinical characteristics and laboratory results of all eligible patients for the Cholesterol Lowering and Arrhythmias Recurrences after Internal Defibrillator Implantation trial (CLARIDI trial) were used. All patients had documented CAD, an ICD implant and were not yet treated with statins. Coronary risk factors, lipid values, glycated haemoglobin (HbA(1c)) and hs-CRP levels were determined. RESULTS: In the 110 included patients (mean age 68+/-9 years, LVEF 40+/-17%, NYHA class II-III in 47%), a high prevalence of coronary risk factors was documented: current smoking in 18%, body mass index > or =30 kg/m(2) in 16%, blood pressure > or =140/90 mm Hg in 40%, history of diabetes in 12%, and HbA(1c) > or =6% in 16% of patients not known with diabetes. A total cholesterol >175 mg/dl was found in 76% of patients and an LDL cholesterol >100 mg/dl in 83%. Finally, median hs-CRP was 4.8 mg/l (interquartile range 2.5-13.9 mg/l). Hs-CRP values > or =2 mg/l were noted in 83% of all patients and in 68% of patients who had an ICD implant more than 6 months before inclusion. CONCLUSION: In CAD patients with ICD implants, the burden of coronary risk factors is high, often unrecognized and/or under-treated. Persistent inflammation is found in the majority of these patients.

Right atrial thrombus in an asymptomatic hemodialysis patient with malfunctioning catheter and patent foramen ovale.

The creation of an accurate functioning arteriovenous fistula has been a long-lasting problem in the hemodialysis setting. In spite of recent guidelines and largely because of the old age of the current dialysis population and a high incidence of diabetes mellitus, atherosclerosis, and related vascular problems, it is not always possible to create an adequate fistula. In that case, long-term tunneled indwelling central vein catheters are a frequently used alternative. Of the many possible complications related to venous access in hemodialysis patients, catheter dysfunction is the most prevalent. We report a 23-year-old female hemodialysis patient in whom such malfunctioning was followed by echocardiography that revealed a large right atrial thrombus (RAT) in close contact to the tip of a long-term indwelling catheter in the presence of a patent foramen ovale. Although RAT is a rare complication in hemodialysis patients, it has very specific therapeutic implications. The present patient underwent a successful surgical atrial thrombectomy. Our experience underscores that in cases of malfunctioning catheter, echocardiographic screening is mandatory.

The use of Tissue Doppler Imaging for the assessment of changes in myocardial structure and function in inherited cardiomyopathies.

Although there is still a long way to go, our understanding of the genetic basis of cardiomyopathies--dilated or hypertrophic--has significantly improved over the past decade. This new and intriguing era of cardiogenetics has already answered some important questions concerning the pathophysiology of these disorders, but it has also raised some new questions: how do we define "presymptomatic" mutation carriers? Should we treat them? Do we have any diagnostic tools to identify the presymptomatic subjects in those families where the underlying mutation has not been identified yet? To address at least part of these questions, there is a clear need for screening techniques in the early stage of the disease which have to be sensitive and non-invasive. In recent years Tissue Doppler Imaging (TDI) has emerged as a well suited technique for these purposes and several interesting papers on this issue have been published. This paper reviews the findings from TDI in several forms of inherited cardiomyopathy. Although the implementation of this technique in everyday clinical practice still requires some refinement, the results from these studies are encouraging and TDI is likely to be complementary to other established screening tools such as ECG and conventional echocardiography.

Risk factor management in diabetic and non-diabetic patients with coronary heart disease. Findings from the EUROASPIRE I AND II surveys.

AIMS/HYPOTHESIS: We examined risk factor management in diabetic and non-diabetic patients with CHD based on data from EUROASPIRE surveys. METHODS: Consecutive CHD patients aged 70 years or younger were interviewed and examined at least 6 months after hospitalisation for a revascularisation procedure or acute myocardial infarction or ischaemia. Of these patients, 3569 were from the EUROASPIRE I study, undertaken from 1995 to 1996 in nine countries, and 5556 were from the EUROASPIRE II study, conducted between 1999 and 2000 in 15 countries. RESULTS: In EUROASPIRE I and II 18% and 20% of CHD patients respectively had been previously diagnosed with diabetes. Fasting glucose screening raised the prevalence of diabetes in EUROASPIRE II to 28%. In EUROSPIRE II the prevalence of risk factors (known diabetic/non-diabetic) was: current smoking 17%/22 % ( p=0.25); obesity (BMI >/=30 kg/m(2)) 43%/29% ( p<0.001); raised blood pressure (>/=140/90 mm Hg) 57%/49% ( p<0.001); and elevated total cholesterol (>/=5.0 mmol/l) 55%/59% ( p<0.001). The proportion of users of cardiovascular medication was: antiplatelet drugs 83%/86% (NS); beta-blockers 62%/63% (NS); ACE inhibitors 49%/35% ( p<0.001); and lipid-lowering drugs 62%/61% (NS). A comparison of both studies showed that for diabetic and non-diabetic patients the prevalence of smoking had increased somewhat and that the prevalence of obesity had increased clearly. There was no improvement in blood pressure control, but cholesterol control had improved, mainly explained by the increased use of lipid-lowering drugs. CONCLUSIONS/INTERPRETATION: These European surveys show a high prevalence of adverse lifestyles and modifiable risk factors among diabetic and non-diabetic patients with CHD. The risk factor status was more adverse in diabetic patients.

Assesment of LV diastolic filling using color M-mode Doppler echocardiography: validation in new hydoraulic model.

The effect of LV properties on v(p) and the E/v(p) ratio remains a matter of debate. Therefore,the objective of this study is to explore - in a new hydraulic model - the individual contributions of LV relaxation, filling pressure and compliance in changes of E, v(p) and E/v(p) for different stages of diastolic function. A new hydraulic model, consisting of an open cylindrical LA connected to an ellipsoidal LV, is designed. E and v(p) are measured for varying values of tau (45-60-90 ms), LV compliance (0.45-1.35 ml/mmHg) and filling pressure (3-10-30 mmHg). The results are used for predicting the evolution of E, v(p) and E/v(p) during different stages of diastolic function. An increase in compliance decreases E, whereas it augments v(p). v(p) is less load-dependent than E. E decreases with delayed relaxation, increases for the case of pseudonormalisation, and becomes higher than the reference values during restrictive filling. The v(p) value is lower for the case of delayed relaxation than for the reference situation. During pseudonormalisation, the value of v(p) remains lower than the reference value but higher than the value for delayed relaxation. v(p) further decreases during restrictive filling. In conclusion, the effect of simultaneous changes in compliance and loading counterbalance changes in v(p). Therefore, under normal physiologic conditions where load and compliance are coupled, v(p) is apparently load-intensive and E/v(p) increases as filling pressure increases. Moreover, in the different stages of diastolic dysfunction, due to the interference of the co-varying relaxation, the increase in E/v(p) is more pronounced.