The multi-societal European consensus on the terminology, diagnosis and management of patients with synchronous colorectal cancer and liver metastases:an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE

Background: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases with a focus on terminology, diagnosis and management. Methods: This project was a multi-organisational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis and management. Statements were refined during an online Delphi process and those with 70% agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising twelve key statements. Results: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term “early metachronous metastases” applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour with “late metachronous metastases” applied to those detected after 12 months. Disappearing metastases applies to lesions which are no longer detectable on MR scan after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways including systemic chemotherapy, synchronous surgery and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. Conclusions: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases

A prospective survey in European Society of Cardiology member countries of atrial fibrillation management: baseline results of EURO bservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry

Aims: Given the advances in atrial fibrillation (AF) management and the availability of new European Society of Cardiology (ESC) guidelines, there is a need for the systematic collection of contemporary data regarding the management and treatment of AF in ESC member countries. Methods and results: We conducted a registry of consecutive in- and outpatients with AF presenting to cardiologists in nine participating ESC countries. All patients with an ECG-documented diagnosis of AF confirmed in the year prior to enrolment were eligible. We enroled a total of 3119 patients from February 2012 to March 2013, with full data on clinical subtype available for 3049 patients (40.4% female; mean age 68.8 years). Common comorbidities were hypertension, coronary disease, and heart failure. Lone AF was present in only 3.9% (122 patients). Asymptomatic AF was common, particularly among those with permanent AF. Amiodarone was the most common antiarrhythmic agent used (~20%), while beta-blockers and digoxin were the most used rate control drugs. Oral anticoagulants (OACs) were used in 80% overall, most often vitamin K antagonists (71.6%), with novel OACs being used in 8.4%. Other antithrombotics (mostly antiplatelet therapy, especially aspirin) were still used in one-third of the patients, and no antithrombotic treatment in only 4.8%. Oral anticoagulants were used in 56.4% of CHA 2DS2-VASc = 0, with 26.3% having no antithrombotic therapy. A high HAS-BLED score was not used to exclude OAC use, but there was a trend towards more aspirin use in the presence of a high HAS-BLED score. Conclusion: The EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot Registry has provided systematic collection of contemporary data regarding the management and treatment of AF by cardiologists in ESC member countries. Oral anticoagulant use has increased, but novel OAC use was still low. Compliance with the treatment guidelines for patients with the lowest and higher stroke risk scores remains suboptimal. © The Author 2013

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Detection of multivessel disease post myocardial infarction using an exercise-induced QRS score

Objective: The aim of this study was to investigate the ability of Athens QRS score values to detect stenoses in other coronary arteries than the obstructed ones (which caused the myocardial infarction [MI]) in patients with a history of MI. Methods: We studied 125 patients (93 males and 32 females, mean age 54 +/- 7 years [range 4568 years]) with a history of MI (46 patients with anterior MI, 54 patients with inferior MI, 25 patients with lateral MI). All patients underwent treadmill exercise testing and coronary arteriography. Results: Athens QRS score values were inversely related to the extent of CAD: -0.5 +/- 0.3 mm for patients with 1-VD (obstructed vessel), -3.4 +/- 2.2 mm for patients with 2-VD (obstructed vessel and stenosis in another vessel), and -5 +/- 1.8 mm for patients with 3-VD (obstructed vessel and stenoses in two more vessels). The ROC curves for the detection of multivessel disease showed that the area under the curve for QRS score values &lt; -3 mm is significantly higher than the curve for ST-segment depression greater than or equal to1 mm (0.948 vs 0.792, P &lt; 0.001). Conclusions: Values of the Athens QRS score less than -3 may distinguish single- from multivessel coronary artery disease in patients with a history of MI

Exercise testing in asymptomatic patients with heterozygous familial hypercholesterolaemia

Objective Familial hypercholesterolaemia (FH) is a frequent genetic disorder in Europe, affecting one in 500 people in its heterozygous form. Both homozygous and heterozygous forms are correlated with increased incidence of cardiovascular events. Methods We investigated clinical and biochemical parameters possibly associated with the results of exercise testing (ET) in asymptomatic patients with heterozygous FH. The study population was derived from outpatients of the Lipid Center in our department and consisted of 194 patients with heterozygous FH who had no medical history of coronary artery disease (CAD) or angina-like symptoms and who had agreed to undergo ET. Results Sex, body mass index, smoking status, diabetes mellitus, family history of CAD, presence of xanthomas and total cholesterol, triglyceride, low-density and high-density lipoprotein cholesterol, apolipoproteins A and B and lipoprotein (a) levels did not differ significantly between patients with positive and negative ET. Higher fibrinogen levels, arterial hypertension and family history of CAD were more frequent among patients with positive ET. However, in multivariate analysis adjusted for all the aforementioned variables, only high fibrinogen levels were significantly and independently associated with a positive result of ET. Conclusions Lipid and coronary risk factor profiles do not seem to predict exercise-induced myocardial ischaemia in asymptomatic patients with heterozygous FH. However, in this high-risk population for cardiovascular events, fibrinogen levels are an independent predictor of positive ET. The adverse effects of FH on the cardiovascular system may be partly mediated by coagulability factors, whose role in the management of FH patients remains to be fully clarified. (C) 2004 Lippincott Williams Wilkins

A QRS score versus ST-segment changes during exercise testing: which is the most reliable ischaemic marker after myocardial revascularisation?

Background The diagnostic ability of exercise testing based on ST-segment changes is low for the detection of restenosis after percutaneous transluminal coronary angioplasty (PTCA) or ischaemia after bypass surgery (CABG). The aim of this study was to improve the diagnostic accuracy of exercise testing in patients with a history of PTCA or CABG, with the implementation of a QRS score. Methods We studied 128 post-PTCA patients (aged 49 8 years) and 104 post-CABG patients (aged 54 +/- 8 years), who had either positive exercise tests with or without angina, or negative exercise tests with continuing angina-like symptoms, and underwent cardiac catheterisation. Results The univariate risk ratio of exercise-induced ST-segment deviation to detect restenosis was 3.05 (p = 0.005) and 0.83 (p = 0.690) in group A and group B patients, respectively. The univariate risk ratios of abnormal QRS score values to detect restenosis were 32.1 (p &lt; 0.001) and 18.8 (p &lt; 0.001) for group A and group B patients, respectively. The univariate risk ratios of the combination of exercise-induced ST-segment changes and of abnormal QRS score values to detect restenosis was 9.43 (p &lt; 0.001) and 3.77 (p &lt; 0.044) for group A and group B patients, respectively. The value of the area under the ROC curves is higher for the QRS score in group A patients, group B patients and for the whole study population. Conclusions QRS score values significantly improve the diagnostic ability of ST-segment change-based exercise testing, for the assessment of restenosis after PTCA or ischaemia after CABG. (C) 2003 Lippincott Williams Wilkins

Non-isotopic RNase cleavage assay for mutation detection in MEFV, the gene responsible for familial Mediterranean fever, in a cohort of Greek patients

Background: The MEFV gene is responsible for familial Mediterranean fever (FMF). Several disease associated mutations have been identified. The range of genetic variation in MEFV in Greek patients has not been determined. Objective: To describe a method that facilitates the routine screening of the entire coding sequence of MEFV (excluding exon 1). Methods: The non-isotopic RNase cleavage assay (NIRCA) was optimised and used as a first step screening method to screen exons 2 to 10 of MEFV. Exons 2 and 10 were analysed separately at DNA level, while exons 3 to 9 were analysed together at cDNA level. The sample group consisted of 26 FMF patients diagnosed using established clinical criteria, six asymptomatic relatives, 12 patients with atypical clinical manifestations, nine patients suffering from various inflammatory diseases, and three normal individuals. All were analysed by NIRCA for mutations in the MEFV gene and direct sequencing was applied subsequently to confirm the results. Results: MEFV mutations were identified in 25 of 26 typical FMF patients and in two of 12 patients with atypical manifestations. NIRCA results were in concordance with sequencing findings in all sequences analysed, suggesting that the method is highly reliable in this disease. Sixteen alterations of MEFV were identified (eight missense mutations and eight single nucleotide polymorphisms). Conclusions: NIRCA can be used for rapid screening of the coding sequence of the MEFV gene in patients suspected of suffering from FMF