Ticagrelor induced systemic inflammatory response syndrome.

BACKGROUND: Ticagrelor is a reversible and direct-acting oral antagonist of the adenosine diphosphate receptor P2Y12. Possible adenosine-mediated effects of ticagrelor on inflammation are complex and incompletely understood. To our knowledge, ticagrelor-induced systemic inflammatory response syndrome (SIRS) has not yet been described. CASE PRESENTATION: We report the case of an 84 years old patient presenting with SIRS subsequent to initiation of ticagrelor after implantation of two drug eluting stents. A broad diagnostic work-up for alternative causes and therapeutic measures were unrevealing. Discontinuation of the agent was followed by rapid improvement in clinical and laboratory signs of SIRS. CONCLUSIONS: After exclusion of other causes, ticagrelor needs to be considered as a possible causative agent for SIRS. Due to the widespread use of ticagrelor, clinicians should be aware of this possible adverse drug reaction.

Long-term efficacy and safety of biodegradable-polymer biolimus-eluting stents: main results of the Basel Stent Kosten-Effektivitäts Trial-PROspective Validation Examination II (BASKET-PROVE II), a randomized, controlled noninferiority 2-year outcome trial.

BACKGROUND: Biodegradable-polymer drug-eluting stents (BP-DES) were developed to be as effective as second-generation durable-polymer drug-eluting stents (DP-DES) and as safe >1 year as bare-metal stents (BMS). Thus, very late stent thrombosis (VLST) attributable to durable polymers should no longer appear. METHODS AND RESULTS: To address these early and late aspects, 2291 patients presenting with acute or stable coronary disease needing stents ≥3.0 mm in diameter between April 2010 and May 2012 were randomly assigned to biolimus-A9-eluting BP-DES, second-generation everolimus-eluting DP-DES, or thin-strut silicon-carbide-coated BMS in 8 European centers. All patients were treated with aspirin and risk-adjusted doses of prasugrel. The primary end point was combined cardiac death, myocardial infarction, and clinically indicated target-vessel revascularization within 2 years. The combined secondary safety end point was a composite of VLST, myocardial infarction, and cardiac death. The cumulative incidence of the primary end point was 7.6% with BP-DES, 6.8% with DP-DES, and 12.7% with BMS. By intention-to-treat BP-DES were noninferior (predefined margin, 3.80%) compared with DP-DES (absolute risk difference, 0.78%; -1.93% to 3.50%; P for noninferiority 0.042; per protocol P=0.09) and superior to BMS (absolute risk difference, -5.16; -8.32 to -2.01; P=0.0011). The 3 stent groups did not differ in the combined safety end point, with no decrease in events >1 year, particularly VLST with BP-DES. CONCLUSIONS: In large vessel stenting, BP-DES appeared barely noninferior compared with DP-DES and more effective than thin-strut BMS, but without evidence for better safety nor lower VLST rates >1 year. Findings challenge the concept that durable polymers are key in VLST formation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01166685.

Minimal invasive retrieval of dislodged Amplatzer occluder with subsequent impediments.

A 47-year-old female underwent interventional patent foramen ovale (PFO) closure with an Amplatzer septal occluder (AGA Medical Corporation, USA). After 48 hours of implantation, she experienced intermittent pulse synchronous retrosternal pain. Subsequently, device-associated compression of the aortic root was diagnosed. Occluder retrieval and surgical PFO-closure was accomplished successfully via minimal invasive, video-assisted anterolateral thoracotomy.

Additional cross-sectional transesophageal echocardiography views improve perioperative right heart assessment.

BACKGROUND: Right heart failure is an important cause of perioperative morbidity and mortality, and transesophageal echocardiography (TEE) is crucial for its diagnosis. However, only four of the 20 cross-sectional views recommended in current guidelines for intraoperative TEE focus on the right heart. This study analyzed whether incorporating additional views into the standard TEE examination improves assessment of the right heart. METHODS: Sixty patients underwent standard TEE examination after induction of anesthesia. In addition, five views focusing on the right heart were acquired. Offline analysis tested: (1) whether the additional TEE views can be acquired as reliably as standard views including parts of the right heart; whether incorporating additional views improves the assessment of (2) eight or more right ventricular wall segments based on a predefined nine-segment model; (3) the tricuspid or pulmonary valve in two or more planes; and (4) transvalvular tricuspid and pulmonary flow in orthograde fashion. RESULTS: Additional views could be imaged as reliably (88%) as standard views (90%). Incorporating some of the additional views allowed the assessment of eight or more right ventricular segments in 59 (98%) versus 18 patients (30%) by the standard views alone, and of the pulmonary valve in two or more planes in 60 (100%) versus 15 patients (25%). Several additional views improved orthograde assessment of transvalvular pulmonary flow, but not of tricuspid flow. CONCLUSIONS: The additional TEE views focusing on the right heart can be acquired as reliably as standard views. Incorporating three of them into the standard TEE examination improves comprehensive assessment of the right heart.

Cardiovascular magnetic resonance imaging for diagnosis and clinical management of suspected cardiac masses and tumours.

AIMS: To evaluate the diagnostic accuracy of cardiovascular magnetic resonance (CMR) imaging from a risk-stratification and therapeutic-management perspective in patients with suspected cardiac tumours. METHODS AND RESULTS: Cardiovascular magnetic resonance exams of 41 consecutive patients (aged 61 ± 14 years, 21 men) referred for evaluation of a suspected cardiac mass were reviewed for tumour morphology and signal characteristics in various unenhanced and contrast-enhanced sequences. Cardiovascular magnetic resonance-derived diagnosis and treatment were compared with clinical outcome and histology in patients undergoing surgery or autopsy (n = 20). In 18 of 41 patients, CMR excluded masses or reclassified them as normal variants; all were treated conservatively. In 23 of 41 patients, CMR diagnosed a neoplasm (14 'benign', 8 'malignant', and 1 'equivocal'); 18 of these patients were operated on, 2 managed conservatively, and 3 by palliation. During follow-up of 705 (inter-quartile range 303-1472) days, 13 patients died. No tumour-related deaths occurred in conservatively managed patients. Patients with a CMR-based diagnosis and treatment of benign tumour had a similar survival as patients without detectable tumour. Compared with histology, CMR correctly classified masses as 'benign or malignant' in 95% of the cases. Tumour perfusion, invasiveness, localization, and pericardial fluid were valuable to distinguish between malignant and benign tumours. Soft tissue contrast and signal intensity patterns in various sequences were valuable for excluding neoplastic lesions and helped to obtain tissue characterization at the histological level in selected tumour cases, respectively. CONCLUSION: Comprehensive CMR provides a confident risk-stratification and clinical-management tool in patients with suspected tumours. Patients where CMR excludes tumours can be managed conservatively.

Functional assessment of the left atrium by real-time three-dimensional echocardiography using a novel dedicated analysis tool: initial validation studies in comparison with computed tomography.

AIMS: A novel real-time three-dimensional echocardiography (RT3DE) analysis tool specifically designed for evaluation of the left atrium enables comprehensive evaluation of left atrial (LA) size, global, and regional function using a dynamic 16-segment model. The aim of this study was the initial validation of this method using computed tomography (CT) as the method of reference. METHODS AND RESULTS: The study population consisted of 34 prospectively enrolled patients with clinical indication for pulmonary vein isolation. A dynamic polyhedron model of the left atrium was generated using RT3DE. LA maximum and minimum volumes (LA(max)/LA(min)) and emptying fraction (LAEF) were determined and compared with the results obtained by CT. High correlations between RT3DE and CT were found for LA(max) (r = 0.92, P < 0.001), LA(min) (r = 0.95, P < 0.001), and LAEF (r = 0.82, P < 0.001). LA(max) and LA(min) were lower by RT3DE than by CT (95.0 ± 44.7 vs. 119.8 ± 50.5 mL, P < 0.001 and 58.1 ± 41.3 vs. 83.3 ± 52.6 mL, P < 0.001, respectively), whereas LAEF was measured higher by RT3DE (42.8 ± 15.2 vs. 34.2 ± 15.4%, P < 0.001, respectively). RT3DE measurements closely correlated in terms of intra-observer (intra-class correlation r = 0.99, r = 0.99, r = 0.96, respectively) and inter-observer variability (r = 0.97, r = 0.98, r = 0.88, respectively). CONCLUSIONS: LA volumes and EF as assessed by RT3DE correlate highly with CT measurements, albeit there is some bias between the imaging modalities. Most importantly, RT3DE measurements using the novel dedicated LA analysis tool are robust in terms of observer variability and thus suitable for follow-up analyses.

Thromboembolic acute myocardial infarction in a congenital double chambered left ventricle.

A 61-year-old woman with a congenital double-chamber left ventricle (DCLV) was admitted because of an anterior ST-elevation myocardial infarction (STEMI). Urgent coronary angiography showed a thrombotic occlusion of the distal part of the left anterior descending artery (LAD). The left ventricular injection revealed a slightly reduced ejection fraction, antero-apical akinesia and an accessory chamber. Two dimensional and three dimensional echocardiography showed anterior akinesia with an accessory chamber at the apex which was separated by a fibromuscular ridge distal to the papillary muscles. The DCLV with myocardial contraction in the additional chamber was originally diagnosed seven years ago during a routine follow-up echocardiography in the course of management for thyroid cancer and at that time left ventricular function was described to be normal. Thromboembolism was assumed to have originated from the hypocontractile left accessory chamber and the patient was set on oral anticoagulation. During follow-up global left ventricular function normalized.

[Heart failure in the elderly]. / Herzinsuffizienz im Alter.

The prevalence of heart failure substantially increases with advancing age. Nevertheless, heart failure in the elderly is commonly under-diagnosed, because dyspnoea and fatigue are often attributed to the natural process of aging. Age-related alterations of the cardiovascular system and the presence of multiple comorbidities not only change the clinical features of heart failure, but also have an impact on heart failure treatment in this population. Cautious uptitration of the individual drugs and vigorous clinical and laboratory monitoring is mandatory to avoid undesired side effects. Although guideline-recommended heart failure therapy is derived from trials that included mainly middle-aged patients with few comorbidities, it has proven beneficial even in the very elderly. Today, guideline-recommended heart failure therapy is still too often withheld from elderly patients out of fear of potential side effects.

Predictors of early readmission or death in elderly patients with heart failure.

BACKGROUND: Contemporary heart failure (HF) patients are elderly and have a high rate of early rehospitalization or death, resulting in a high burden for both the patients and the health care system. Prior studies were focused on younger and less well-characterized patients. We aimed to identify predictors of early hospital readmission and death in elderly patients with HF. METHODS: Patients with chronic HF taking part in the TIME-CHF study (n = 614, age 77 +/- 8 years, 41% female, left ventricular ejection fraction 35% +/- 13%) were evaluated with respect to predictors of hospital readmission or death 30 and 90 days after inclusion. Demographic, clinical, laboratory, echocardiographic, and social variables were obtained at baseline and included in a multivariable logistic regression analysis to identify predictors of early events. RESULTS: The rate of hospital readmission or death was high at 30 (11%) and 90 days (26%). The reason for hospitalization was HF in 33%, other cardiovascular in 32%, and noncardiovascular in 45% of the cases, respectively. Predictors of readmission or death at 30 days were angina, lower systolic blood pressure, anemia, more extensive edema, higher creatinine levels, and dry cough; and at 90 days were coronary artery disease, prior pacemaker implantation, high jugular venous pressure, pulmonary rales, prior abdominal surgery, older age, and depressive symptoms. CONCLUSIONS: Early hospital readmission or death was frequent among elderly HF patients. A very large proportion of readmissions were due to noncardiovascular causes. In addition to clinical signs of HF, comorbidities are important predictors of early events in elderly HF patients.

Copeptin and risk stratification in patients with acute dyspnea.

INTRODUCTION: The identification of patients at highest risk for adverse outcome who are presenting with acute dyspnea to the emergency department remains a challenge. This study investigates the prognostic value of Copeptin, the C-terminal part of the vasopressin prohormone alone and combined to N-terminal pro B-type natriuretic peptide (NT-proBNP) in patients with acute dyspnea. METHODS: We conducted a prospective, observational cohort study in the emergency department of a university hospital and enrolled 287 patients with acute dyspnea. RESULTS: Copeptin levels were elevated in non-survivors (n = 29) compared to survivors at 30 days (108 pmol/l, interquartile range (IQR) 37 to 197 pmol/l) vs. 18 pmol/l, IQR 7 to 43 pmol/l; P < 0.0001). The areas under the receiver operating characteristic curve (AUC) to predict 30-day mortality were 0.83 (95% confidence interval (CI) 0.76 to 0.90), 0.76 (95% CI 0.67 to 0.84) and 0.63 (95% CI 0.53 to 0.74) for Copeptin, NT-proBNP and BNP, respectively (Copeptin vs. NTproBNP P = 0.21; Copeptin vs. BNP P = 0.002). When adjusted for common cardiovascular risk factors and NT-proBNP, Copeptin was the strongest independent predictor for short-term mortality in all patients (HR 3.88 (1.94 to 7.77); P < 0.001) and especially in patients with acute decompensated heart failure (ADHF) (HR 5.99 (2.55 to 14.07); P < 0.0001). With the inclusion of Copeptin to the adjusted model including NTproBNP, the net reclassification improvement (NRI) was 0.37 (P < 0.001). An additional 30% of those who experienced events were reclassified as high risk, and an additional 26% without events were reclassified as low risk. CONCLUSIONS: Copeptin is a new promising prognostic marker for short-term mortality independently and additive to natriuretic peptide levels in patients with acute dyspnea.

Current variables, definitions and endpoints of the European cardiovascular magnetic resonance registry.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is increasingly used in daily clinical practice. However, little is known about its clinical utility such as image quality, safety and impact on patient management. In addition, there is limited information about the potential of CMR to acquire prognostic information. METHODS: The European Cardiovascular Magnetic Resonance Registry (EuroCMR Registry) will consist of two parts: 1) Multicenter registry with consecutive enrolment of patients scanned in all participating European CMR centres using web based online case record forms. 2) Prospective clinical follow up of patients with suspected coronary artery disease (CAD) and hypertrophic cardiomyopathy (HCM) every 12 months after enrolment to assess prognostic data. CONCLUSION: The EuroCMR Registry offers an opportunity to provide information about the clinical utility of routine CMR in a large number of cases and a diverse population. Furthermore it has the potential to gather information about the prognostic value of CMR in specific patient populations.

Routine echocardiography after radiofrequency ablation: to flog a dead horse?

AIMS: Radiofrequency ablation (RFA) is frequently used to treat sustained arrhythmias. One major complication is pericardial effusion-tamponade. Therefore, many centres perform echocardiography after interventions, but data on necessity of such routine procedures are scarce. METHODS AND RESULTS: We included 510 patients with RFA and compared echocardiographic results acquired before and <24 h after intervention. We defined pericardial effusion as 'small', if <10 mm in diastole, 'moderate' if >10 mm, 'large' if >20 mm, or tamponade (>20 mm with haemodynamic compromise). Age was 55 +/- 16 years, 40% were females. Thirty-five percentage underwent RFA for atrioventricular nodal re-entrant tachycardia (AVNRT), 28% for atrial flutter, 15% for atrial fibrillation (AF), 12% for Wolff-Parkinson-White (WPW) syndrome, and 10% for different other arrhythmias. In 16 patients (3.2%), small asymptomatic effusions were detected. The only moderate effusion was suspected due to procedure circumstances. Radiofrequency ablation for AF had a higher incidence compared to AVNRT and flutter (P = 0.001 and <0.0001, respectively) or to WPW syndrome (P = 0.06). CONCLUSION: Numbers of significant pericardial effusion as detected by routine echocardiography were low (3.6%) and clinically relevant effusions absent. We thus recommend performing echocardiography after RFA only, if effusion is suspected clinically or if RFA was performed for AF, due to the high incidence of effusions with this type of ablation.

Drug-eluting stents compared with bare metal stents improve late outcome after saphenous vein graft but not after large native vessel interventions.

OBJECTIVES: To define long-term efficacy of different stent types in saphenous vein graft (SVG) interventions. METHODS: In BASKET (Basel Stent Cost Effectiveness Trial), major adverse cardiac events (MACE), i.e. cardiac death, myocardial infarction and symptom-driven target vessel revascularization (TVR) were assessed after 18 months comparing drug-eluting stents (DES) versus bare metal stents (BMS), and SVG and large native vessels (> or =3.0 mm). RESULTS: Large vessel interventions were performed in 605 patients. Patients with SVG interventions (n = 47, 8%) were older and had more often hypertension, prior myocardial infarction, prior revascularization and multivessel disease and less frequent ST-elevation myocardial infarction than patients with large native vessel interventions (n = 558, 92%). Stent number and length were higher in SVG than in large native vessel interventions. Baseline characteristics were similar for DES and BMS. In SVG stenting, long-term outcome was better in DES- than in BMS-treated patients (MACE 21 vs. 62%, p = 0.007, mainly due to TVR 18 vs. 46%, p = 0.045), but for large native vessel stenting, no significant difference was noted (MACE: 13 vs. 16%, p = 0.40). CONCLUSIONS: Among patients with SVG disease, treatment with DES resulted in a better long-term outcome than treatment with BMS. In contrast, no DES benefit was found in similarly sized native vessels regarding MACE.

Value of brain natriuretic peptides in primary care patients with the clinical diagnosis of chronic heart failure.

INTRODUCTION: Brain natriuretic peptide (BNP) and N-Terminal pro natriuretic peptide (NT-proBNP) are widely accepted to diagnose congestive heart failure (CHF) in the emergency room. The aim of this study was to evaluate the value of BNP and NT-proBNP to diagnose CHF in primary care. METHODS: Clinical and Doppler-echocardiographic assessment of patients referred by their general practitioner (GP) with the diagnosis of CHF. Receiver operating curves were used to evaluate the accuracy of BNP and NT-proBNP for echocardiographically confirmed systolic and/or diastolic heart failure. RESULTS: Three hundred and eighty four patients (mean age of 65) were included. One hundred and ninety three (50%) patients had systolic heart failure and 31 (8%) had isolated diastolic heart failure. Using currently recommended cut-off values of BNP (less than 100 pg/ml) and NT-proBNP (less than 125 pg/ml) for exclusion of CHF, BNP was false negative in 25% and NT-proBNP in 10% of the patients. The area under the curve was better for NT-proBNP than for BNP (0.742 vs. 0.691). CONCLUSION: In this population with a high prevalence of CHF, BNP and NT-proBNP failed to adequately rule out CHF. GP's should be cautious when using BNP and NT-proBNP in primary care. An echocardiography remains compulsory in unexplained dyspnea.

Detection of intake of nonsteroidal anti-inflammatory drugs in elderly patients with heart failure. How to ask the patient?

PRINCIPLES: Heart failure hospitalisations may be related to non-steroidal anti-inflammatory drug (NSAID) use. Since NSAIDs are usually prescribed by general practitioners or taken without prescription, their use may be largely underestimated. Therefore, we assessed the impact of a focussed analgesic medication history as compared to a usual medication history on detection of NSAID intake in elderly heart failure patients and the potential effect of medical advice on discontinuation of this therapy in a non-controlled study design. METHODS: A structured and stepwise history of analgesic intake (firstly open questioning about medication intake, secondly with a focus on analgesic intake, finally focussing on behaviour in case of pain) was done in 197 elderly heart failure patients taking part in the TIME-CHF study at baseline and up to 3 follow-up visits. All participants were informed about the potential hazardous effects of NSAIDs and alternative analgesic therapy was proposed in case of NSAID intake. Patients were aged 60 years or older with clinical signs of heart failure NYHA > or =II, elevated NT-BNP, and had been hospitalised due to heart failure within the last year. Details of this study have been described previously. RESULTS: At baseline, 43 patients (22%) were taking NSAID. Almost half (n = 19) taking NSAID reported the use only after specific questioning. Therefore, a focussed analgesic medication history was superior as compared to a usual medication history to detect patients taking NSAIDs (22% vs 12%; p <0.001). After instruction and proposal of alternative analgesic therapy, NSAID intake dropped from 22% to 7% (p <0.001). No risk factor for continuous use was identified. CONCLUSIONS: NSAID use in heart failure patients is relatively common. Specific questioning may help to increase detection of NSAID intake and information on its hazardous effects to decrease NSAID use.

BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial.

CONTEXT: It is uncertain whether intensified heart failure therapy guided by N-terminal brain natriuretic peptide (BNP) is superior to symptom-guided therapy. OBJECTIVE: To compare 18-month outcomes of N-terminal BNP-guided vs symptom-guided heart failure therapy. DESIGN, SETTING, AND PATIENTS: Randomized controlled multicenter Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) of 499 patients aged 60 years or older with systolic heart failure (ejection fraction < or = 45%), New York Heart Association (NYHA) class of II or greater, prior hospitalization for heart failure within 1 year, and N-terminal BNP level of 2 or more times the upper limit of normal. The study had an 18-month follow-up and it was conducted at 15 outpatient centers in Switzerland and Germany between January 2003 and June 2008. INTERVENTION: Uptitration of guideline-based treatments to reduce symptoms to NYHA class of II or less (symptom-guided therapy) and BNP level of 2 times or less the upper limit of normal and symptoms to NYHA class of II or less (BNP-guided therapy). MAIN OUTCOME MEASURES: Primary outcomes were 18-month survival free of all-cause hospitalizations and quality of life as assessed by structured validated questionnaires. RESULTS: Heart failure therapy guided by N-terminal BNP and symptom-guided therapy resulted in similar rates of survival free of all-cause hospitalizations (41% vs 40%, respectively; hazard ratio [HR], 0.91 [95% CI, 0.72-1.14]; P = .39). Patients' quality-of-life metrics improved over 18 months of follow-up but these improvements were similar in both the N-terminal BNP-guided and symptom-guided strategies. Compared with the symptom-guided group, survival free of hospitalization for heart failure, a secondary end point, was higher among those in the N-terminal BNP-guided group (72% vs 62%, respectively; HR, 0.68 [95% CI, 0.50-0.92]; P = .01). Heart failure therapy guided by N-terminal BNP improved outcomes in patients aged 60 to 75 years but not in those aged 75 years or older (P < .02 for interaction) CONCLUSION: Heart failure therapy guided by N-terminal BNP did not improve overall clinical outcomes or quality of life compared with symptom-guided treatment. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN43596477.

[Noninvasive diagnostic of coronary artery disease]. / Die nichtinvasive Bilddiagnostik der koronaren Herzkrankheit.

Noninvasive imaging of coronary artery disease has extensively evolved during the last decade. Today, at least four imaging techniques with excellent image quality such as echocardiography, myocardial perfusion scintigraphy and PET, cardiac magnetic resonance and cardiac CT are widely available in order to estimate the risk for future ischemic events, to corroborate the suspected diagnosis of coronary artery disease, to demonstrate the extent and localisation of myocardial ischemia, to diagnose myocardial infarction and measure it's size, to identify the myocardium at risk during acute ischemia, to differentiate between viable and nonviable myocardium and thereby provide the basis for indications of revascularisations, to follow revascularized patients over long time, to assess the risk for sudden cardiac death and the development of heart failure after myocardial infarction and to depict atheromatosis and atherosclerosis of the coronary artery tree. Echocardiography is the most widely used imaging method in cardiology. It provides excellent information on morphology and function of nearly all cardiac structures. Stress echocardiography has been proven to be a reliable tool for the demonstration of myocardial ischemia and for the acquisition of prognostic data. Newer ultrasound techniques may further improve investigator dependence and thereby reproducibility. The completeness of echocardiography will always depend on acoustic windows, which are given in a specific patient. Myocardial perfusion scintigraphy provides the largest database especially on prognosis in coronary artery disease. It has been the <> for the depictions of ischemic and infarcted myocardium. Radiation exposure will always be an issue. Newer hybrid techniques combining nuclear methods with cardiac CT may add arguments, which will be needed for clinical decision-making. Cardiac magnetic resonance has evolved as an important tool in the diagnosis of cardiovascular diseases. It is investigator independent, does not apply any biologically hazardous energy and has the largest potential for tissue characterization due to its high contrast resolution. It therefore is an excellent technique to investigate all the aspects of coronary artery disease. Its availability is increasing, however in order to fully utilize its large potential an optimal collaboration among -specialist (cardiologists, radiologists, physicists) is mandatory. Cardiac CT has evolved as an excellent method for the depiction of the coronary arteries. Due to its high spatial and time resolution it provides high quality luminography of the coronaries and newer technique are also -investigating plaque composition of diseased coronary arteries. Overestimation of coronary artery stenosis in calcified vessels is an inherent problem of the technique and the risk of radiation exposure has to be weighted against the benefit of non-invasively depicting the coronary arteries. It will be the future task of all specialists in this field to define the most efficient and cost-effective way to apply these excellent techniques for the investigation of all the different aspects of patients with coronary artery disease.

Cost-effectiveness of drug-eluting stents in patients at high or low risk of major cardiac events in the Basel Stent KostenEffektivitäts Trial (BASKET): an 18-month analysis.

BACKGROUND: Our aim was to determine whether drug-eluting stents are good value for money in long-term, everyday practice. METHODS: We did an 18-month cost-effectiveness analysis of the Basel Stent KostenEffektivitäts Trial (BASKET), which randomised 826 patients 2:1 to drug-eluting stents (n=545) or to bare-metal stents (281). We used non-parametric bootstrap techniques to determine incremental cost-effectiveness ratios (ICERs) of drug-eluting versus bare-metal stents, to compare low-risk (> or =3.0 mm stents in native vessels; n=558, 68%) and high-risk patients (<3.0 mm stents/bypass graft stenting; n=268, 32%), and to do sensitivity analyses by altering costs and event rates in the whole study sample and in predefined subgroups. Quality-adjusted life-years (QALYs) were assessed by EQ-5D questionnaire (available in 703/826 patients). FINDINGS: Overall costs were higher for patients with drug-eluting stents than in those with bare-metal stents (11,808 euros [SD 400] per patient with drug-eluting stents and 10,450 euros [592] per patient with bare-metal stents, mean difference 1358 euros [717], p<0.0001), due to higher stent costs. We calculated an ICER of 64,732 euros to prevent one major adverse cardiac event, and of 40,467 euros per QALY gained. Stent costs, number of events, and QALYs affected ICERs most, but unrealistic alterations would have been required to achieve acceptable cost-effectiveness. In low-risk patients, the probability of drug-eluting stents achieving an arbitrary ICER of 10,000 euros or less to prevent one major adverse cardiac event was 0.016; by contrast, it was 0.874 in high-risk patients. INTERPRETATION: If used in all patients, drug-eluting stents are not good value for money, even if prices were substantially reduced. Drug-eluting stents are cost effective in patients needing small vessel or bypass graft stenting, but not in those who require large native vessel stenting.

Value and limitations of target-vessel ischemia in predicting late clinical events after drug-eluting stent implantation.

UNLABELLED: Drug-eluting stents reduce clinical events related to restenosis but may be complicated by late stent-thrombosis. Whereas assessment of target-vessel ischemia by myocardial perfusion scintigraphy identifies relevant restenosis noninvasively, it is unknown whether this technique may also predict late clinical events related to late stent-thrombosis and to restenosis after drug-eluting stent implantation. METHODS: All 826 patients treated with stenting between May 2003 and May 2004 were included in the Basel Stent Cost Effectiveness Trial (Basel Stent Kosten-Effektivitäts Trial, or BASKET) and randomized (2:1) to drug-eluting stents or bare metal stents. Myocardial scintigraphy was performed on 476 (64%) of 747 patients without major events after 6 mo. Patients were followed for 1 y for cardiac death, nonfatal myocardial infarction, and target-vessel revascularization due to restenosis or late stent-thrombosis. RESULTS: The rate of target-vessel ischemia in these patients was lower with drug-eluting stents than with bare metal stents (5.4% vs. 10.4%, P = 0.045), similar to the rates of symptom-driven target-vessel revascularization up to 6 mo (4.6% vs. 7.8%, P = 0.08). Ischemia was silent in 68%. During follow-up, patients with target-vessel ischemia had higher event rates than did patients without ischemia (32.4% vs. 6.1%, P < 0.001); however, ischemia did not predict late stent-thrombosis (0/11 cases). CONCLUSION: The rate of clinical restenosis assessed scintigraphically was lower with drug-eluting stents than with bare metal stents and paralleled that of symptom-driven target-vessel revascularization. Target-vessel ischemia independently predicted late clinical events related to restenosis but not to late stent-thrombosis.

Dimethyl fumarate, a small molecule drug for psoriasis, inhibits Nuclear Factor-kappaB and reduces myocardial infarct size in rats.

Persistent Nuclear Factor-kappaB (NF-kappaB) activation is hypothesized to contribute to myocardial injuries following ischemia-reperfusion. Because inhibition or control of NF-kappaB signaling in the heart probably confers cardioprotection, we determined the potency of the NF-kappaB inhibitor dimethyl fumarate (DMF) in cardiovascular cells, and determined whether administration of DMF translates into beneficial effects in an animal model of myocardial infarction. In rat heart endothelial cells (RHEC), we analysed inhibitory effects of DMF on NF-kappaB using shift assay and immunohistofluorescence. In in vivo experiments, male Sprague Dawley rats undergoing left coronary artery occlusion for 45 min received either DMF (10 mg/kg body weight) or vehicle 90 min before ischemia as well as immediately before ischemia. After 120 min of reperfusion, the hearts were stained with phthalocyanine blue dye and triphenyltetrazolium chloride. Additionally, acute hemodynamic and electrophysiologic effects of DMF were determined in dose-response experiments in isolated perfused rat hearts. DMF inhibited TNF-alpha-induced nuclear entry of NF-kappaB in RHEC. In in vivo experiments, myocardial infarct size was significantly smaller in rats that had received DMF (20.7%+/-9.7% in % of risk area; n=17) than in control rats (28.2%+/-6.2%; n=15). Dose-response experiments in isolated perfused rat hearts excluded acute hemodynamic or electrophysiologic effects as mechanisms for the effects of DMF. DMF inhibits nuclear entry of NF-kappaB in RHEC and reduces myocardial infarct size after ischemia and reperfusion in rats in vivo. There was no indication that the beneficial effects of DMF were due to acute hemodynamic or electrophysiologic influences.