Lars Ib Andersen

Revascularization Compared to Medical Treatment in Patients with Silent vs. Symptomatic Residual Ischemia after Thrombolyzed Myocardial Infarction – The DANAMI Study

Aims: The aim was to compare the effect of revascularization to conservative treatment in patients with residual silent and with residual symptomatic ischemia following acute myocardial infarction (AMI). The study was a subanalysis of the DANAMI (DANish AMI) randomized study of invasive vs. conservative treatment in patients with inducible ischemia after thrombolysis in AMI. Methods and Results: One thousand and eight patients were randomized to invasive or conservative treatment, stratified by the type of ischemia: silent, i.e. ST depression during an exercise test prior to discharge in 56%, or symptomatic, i.e. chest pain occurring either spontaneously during admission or during the exercise test, with or without ST changes, in 44%. Compared to a conservative strategy, invasive treatment reduced the incidence of nonfatal reinfarction, after in median 2.4 years, in both symptomatic patients (13.3–7.2%, p < 0.006) and patients with silent ischemia (10.1 vs. 5.7%, p < 0.05), and of admissions with unstable angina in symptomatic (44.5–27.6%, p < 0.0001) and silent ischemia (21.6–13.3%, p < 0.0006). Conclusions:Compared to conservative strategy, invasive treatment reduces the risk of nonfatal reinfarction and hospital admissions for unstable angina in thrombolyzed post-AMI patients with silent as well as symptomatic exercise-induced ischemia.

Emergency coronary artery bypass surgery after failed percutaneous transluminal coronary angioplasty.

Coronary complications caused by percutaneous transluminal coronary angioplasty (PTCA) may necessitate emergency coronary artery bypass grafting (CABG). In 1994-1998, 132 patients (1.5% of the patients registered in the Danish PTCA registry) underwent CABG within 24 h because of angioplasty complications. We reviewed the files of 86 patients who had emergency operations within 6 h and found that 35% suffered from 1-vessel disease. Fifty-eight percent were taken directly to the operating room from the cardiovascular laboratory, and 13% were given preoperative cardiovascular resuscitation. The vessels most frequently injured were the right coronary artery and the left anterior descending branch (LAD). The patients received a mean of 2.4 coronary bypasses each. Forty-three percent of the patients with lesions of the left main coronary artery and/or the LAD received a vein graft to the LAD. A perioperative Q-wave myocardial infarction developed in 51% of the patients. The in-hospital mortality rate was 12%. These results are inferior to those obtained after elective surgery. Local cardiothoracic backup is vital when PTCA is performed in an unselected patient group.

Coronary artery bypass grafting within 30 days after treatment of acute myocardial infarctions with angioplasty or fibrinolysis – a surgical substudy of DANAMI‐2

Objective—To calculate the incidence and analyse the indications and outcome after surgical revascularization within the first 30 days after randomization of 1572 patients with acute myocardial infarction (MI) associated with ST‐segment elevation (STEMI). Design—Data regarding the patients undergoing heart surgery within the first 30 days after randomization were collected. Results—Three patients (0.2%) with acute STEMI and randomized to percutaneous coronary intervention (PCI) underwent emergent coronary artery bypass grafting (CABG). A total of 50 patients (3.2%), 30 in the PCI group and 20 in the fibrinolysis group were revascularized by surgery within the first 30 days after randomization. The most frequent indication for surgery in both groups was unstable angina pectoris, followed by left main stenosis. The incidence of postoperative complications was higher compared with the outcome after elective CABG. Conclusions—The incidence of emergency CABG in this study was low (0.2%) after treatment of acute MI with either PCI or fibrinolysis. The overall incidence within 30 days was 3.2%, however, the mortality is increased with a 30‐day mortality of 10% in this high‐risk patient group.

Strategies for Integrated Analysis of Genetic, Epigenetic, and Gene Expression Variation in Cancer: Addressing the Challenges

The development and progression of cancer, a collection of diseases with complex genetic architectures, is facilitated by the interplay of multiple etiological factors. This complexity challenges the traditional single-platform study design and calls for an integrated approach to data analysis. However, integration of heterogeneous measurements of biological variation is a non-trivial exercise due to the diversity of the human genome and the variety of output data formats and genome coverage obtained from the commonly used molecular platforms. This review article will provide an introduction to integration strategies used for analyzing genetic risk factors for cancer. We critically examine the ability of these strategies to handle the complexity of the human genome and also accommodate information about the biological and functional interactions between the elements that have been measured—making the assessment of disease risk against a composite genomic factor possible. The focus of this review is to provide an overview and introduction to the main strategies and to discuss where there is a need for further development.

Prevention of atrial fibrillation in patients with aortic valve stenosis with candesartan treatment after aortic valve replacement

BACKGROUND Accumulating data has suggested that treatment with Angiotensin-II receptor antagonists can prevent the new onset of atrial fibrillation (AF). The aim of this study was to evaluate whether treatment with candesartan on top of conventional treatment could prevent new onset AF in patients with aortic valve stenosis (AS) after aortic valve replacement. METHODS AND RESULTS The study was a single centre, consecutive; investigator initiated study using a prospective randomised blinded endpoint design. 91 patients with severe AS without known AF scheduled for aortic valve replacement (AVR) were randomised to candesartan 32 mg once daily on top of conventional treatment or conventional therapy immediately after AVR. Patients were examined with ECG 3, 6, 9 and 12 months after surgery, and Holter-ECG analysis after 3 and 12 months. Primary endpoint was episode of AF with a duration exceeding 30s, on the ECG or Holter-ECG and/or patients hospitalised due to AF. 14 patients developed new onset AF during follow up. AF-free survival was significantly higher (94% vs 74%, p=0.02) in patients treated with candesartan. CONCLUSION In patients with symptomatic severe AS undergoing AVR, treatment with candesartan may prevent the new onset of atrial fibrillation.

Coronary artery bypass grafting within the first year after treatment of large acute myocardial infarctions with angioplasty or fibrinolysis

Objectives. To calculate the incidence and analyse and outcome after coronary artery bypass grafting (CABG) within the first year after randomisation of 1 572 patients with acute myocardial infarctions with ST-segment elevation (STEMI) to either percutaneous coronary intervention (PCI) or fibrinolysis. Design. The study includes 131 patients: 108 male and 23 female with a mean age 62 years. Results. The total 30-day mortality after CABG was 4.6% (7.5% in the PCI group and 2.6% in the fibrinolysis group). The 30-day mortality was 9.8% after CABG within the first 30-days and 1.3% after CABG within 31–365 days. The patients who were operated early had a reduced EF to 43% as compared to 50% in patients who were not operated or patients having CABG after 30-days (p = 0.002). Conclusion. CABG was performed within the first year after STEMI in 10% of patients randomised to fibrinolysis and in 6.7% of patients randomised to PCI. Patients having CABG within the first 30-days after treatment of STEMI had an increased mortality of 9.8%.

Can preoperative myocardial perfusion scintigraphy predict changes in left ventricular perfusion and function after coronary artery bypass graft surgery

OBJECTIVES We wanted to evaluate whether preoperative myocardial perfusion scintigraphy (MPS) could predict changes in cardiac symptoms and postoperative myocardial perfusion and left ventricular function after coronary artery bypass grafting (CABG). METHODS Ninety-two patients with stable angina pectoris (and at least one occluded coronary artery) underwent MPS before, and 6 months after, undergoing CABG. The result of the MPS was kept secret from the surgeons. RESULTS Before CABG, 90% of the patients had angina. After CABG, 97% of the patients were without symptoms. Overall graft patency was 84%. Before CABG, one patient had normal perfusion; in the rest of them the defects were classified as follows: reversible (60%), partly reversible (27%) and irreversible (12%). Following CABG, 33% had normal perfusion; in the rest the defects were reversible in 29%, partly reversible in 12% and irreversible in 26%. Left ventricular ejection fraction (LVEF), which was normal before operation in 45%, improved in 40% of all patients. The increase in LVEF was not related to the preoperative pattern of perfusion defects. Of 30 patients with normalized perfusion after CABG, 29 (97%) had reversible defects and one patient had partly reversible defects. Of 83 perfusion defects, which were normalized after CABG, 67 were reversible (81%) or partly reversible (12%). Seventy-five percent of all reversible coronary artery territories before CABG were normalized after operation. CONCLUSIONS Our results indicate that reversible or partly reversible perfusion defects at a preoperative MPS have a high chance of normalized myocardial perfusion assessed by MPS 6 months after operation. Normal perfusion is obtained almost exclusively in territories with reversible ischaemia. Symptoms improved in nearly all patients and LVEF in a significant fraction of the patients, not related to preoperative MPS.

Association of miR-548c-5p, miR-7-5p, miR-210-3p, miR-128-3p with recurrence in systemically untreated breast cancer

Current prognostic markers allocate the majority of lymph node (LN) negative and estrogen receptor (ER) positive breast cancer patients into the high-risk group. Accordingly, most patients receive systemic treatments although approximately 40% of these patients may have been cured by surgery and radiotherapy alone. Two studies identified seven prognostic microRNAs in systemically untreated, LN negative and ER positive breast cancer patients which may allow more precise patient classification. However, six of the seven microRNAs were analyzed in both studies but only found to be prognostic in one study. To validate their prognostic potential, we analyzed microRNA expression in an independent cohort (n = 110) using a pair-matched study design minimizing dependence of classical markers. The expression of hsa-miR-548c-5p was significantly associated with abridged disease-free survival (hazard ratio [HR]:1.96, p = 0.027). Contradicting published results, high hsa-miR-516-3p expression was associated with favorable outcome (HR:0.29, p = 0.0068). The association is probably time-dependent indicating later relapse. Additionally, re-analysis of previously published expression data of two matching cohorts (n = 100, n = 255) supports an association of hsa-miR-128-3p with shortened disease-free survival (HR:2.48, p = 0.0033) and an upregulation of miR-7-5p (p = 0.0038; p = 0.039) and miR-210-3p (p = 0.031) in primary tumors of patients who experienced metastases. Further analysis may verify the prognostic potential of these microRNAs.

Angiography-based prediction of outcome after coronary artery bypass surgery versus changes in myocardial perfusion scintigraphy.

OBJECTIVES The present study compared the clinical prediction of the effect of coronary artery bypass grafting (CABG) on coronary blood flow and left ventricular ejection fraction (LVEF) with changes in gated myocardial perfusion scintigraphy. METHODS A prospective group of 92 patients underwent myocardial perfusion scintigraphy before and 6 months after CABG, the results being kept secret from the surgeon. Based on clinical and angiographic findings, the surgeons filled in a questionnaire indicating the predicted changes in coronary blood flow in each of the three coronary artery territories and in the LVEF. RESULTS Symptomatic improvement was present in nearly all the patients. Following CABG, the perfusion defects were reduced in around two-thirds and normalized in one-third of the territories clinically predicted to improve. Improved perfusion for territories not predicted to improve was slightly lower, and correlations between predicted and observed regional changes in coronary blood flow and perfusion defects were poor. LVEF increased (by over five ejection fraction units) in almost half of the patients, but with no correlation between the predicted and the observed changes. CONCLUSIONS Based on clinical and angiographic findings, the marked improvements after CABG in cardiac perfusion and function are poorly predicted.