Tomas Jernberg

Patients with a suspected acute non-ST-elevation myocardial infarctions (NSTEMI) currently undergo invasive coronary angiography (ICA) to identify a potential infarct-related artery (IRA) that become the target for revascularization. However, 25% of patients have no IRA and an identified coronary stenosis may be an en passant finding in a patient with non-ischemic chest pain, i.e. myocarditis or Tako-Tsubo. Cardiac magnetic resonance (CMR) offers non-invasive myocardial tissue characterization and can identify both ischaemic- and non-ischaemic aetiologies for the acute event. Therefore we are performing the Karolinska pilot study for cardiac MRI prior to invasive coronary angiography in patients with suspected NSTEMI (KAPSICA-CMR). This prospective clinical trial tests the hypothesis that implementing novel high-resolution CMR techniques in suspected NSTEMI patients will lead to more accurate diagnosis and the ability to safely rule out the need for an ICA. Patients (n=150) with suspected NSTEMI undergo a CMR before ICA. The CMR is analysed without any clinical or ICA information and is not used to guide ICA or clinical decision making. The CMR is compared with the ICA results and clinical outcome and the health-economic consequences of a CMR first approach will be evaluated. The results of this pilot study will inform a randomized clinical multi-center trial testing the approach of CMR-guided management of patients with suspected NSTEMI.

Background:Left ventricular (LV) thrombus is a serious complication of AMI associated with increased risk of stroke or systemic embolism (SSE). Warfarin has long been the standard treatment, but the better safety profile of the DOACs makes them an attractive alternative to warfarin. In the absense of adequately powered randomized studies, no recommendation for the treatment of LV thrombus is provided.Primary Objective: To evaluate the efficacy of apixaban versus warfarin with respect to thrombus resolution Secondary Objectives: To evaluate the safety and efficacy of apixaban versus warfarin with respect to bleeding outcomes, MACE, NACE, stroke and SSE, and the rate of LV thrombus recurrence at one year. Workplan:Two hundred twelve patients with LV thrombus detected on transthoracic echocardiography (TTE) within 1 to 28 days after an AMI will be randomized 1:1 to apixaban or warfarin. The primary outcome will be evaluated at 3 months. Secondary outcomes as outlined above, will be evaluated at 3 and 12 months.  Significance:It is important to evaluate the use of DOAC (apixaban) for LV thrombus since there are other indications where DOACs were believed to be as effective as warfarin, but randomized trials failed, such as for mechanical heart valves and rheumatic heart disease. If apixaban prove at least non-inferior to warfarin, apixaban would be the preferred drug due to its better safety profile and convenience. This study will inform LV thrombus treatment recommendations.

The objective is to examine whether advanced imaging techniques and AI-based plaque characterization with deep learning algorithms alone or in combination with other biomarkers, including targeted omics, can differentiate between coronary plaques that will cause a type 1 myocardial infarction (MI) and coronary plaques that will not cause a type-1 MI.SCAPIS included 30154 randomly selected men and women. We will create a nested case control study withinSCAPIS with 400 cases that after undergoing CCTA have developed a type 1 MI and controls (n=400, matched forage, sex and time of CCTA) that after undergoing CCTA have not developed type 1 MI. All cases will be carefullyadjudicated and characterized regarding clinical and angiographic findings at the event. The CCTAs performed atbaseline in cases and controls will be analyzed using deep learning algorithms, quantitativemeasurements from commercially available software and modern targeted omics techniques. Models will beoptimized to discriminate between cases and controls. These models can then be validated in the whole SCAPIScohort but also in international CCTA cohorts.By developing methods that can discriminate between coronary plaques that will cause type 1 MI from those that willnot, and use more precise outcome definitions, we can improve understanding regarding underlying mechanisms anddevelop better and more precise methods for risk stratification and identify new treatment targets.

Obesity is associated with type 2 diabetes (T2D) and cardiovascular disease (CVD). Metabolic and bariatric surgery (MBS) has in several randomized controlled trials (RCT) been shown to be superior to best medical therapy in the treatment of T2D. In the area of CVD, RCT after MBS are lacking. We recently demonstrated in a cohort study that MBS in patients with severe obesity and a previous myocardial infarction (MI) was associated with a 50% reduction in the risk of death and new MI. The aim of this proposal is to confirm this in a nationwide RCT. Using the nationwide SWEDEHEART database we will identify patients with serve obesity and a previous MI. They will be contacted and offered participation. After informed consent the patients will be randomized to MBS or optimized care (including visit with a cardiologist and optimization of secondary preventive measures and referral to dietician/physiotherapist). The primary outcome measure is a major cardiovascular adverse event (MACE). Secondary outcome measures include mortality, new MI, stroke, heart failure and atrial fibrillation. Tertiary outcome measures include health related quality of life and surgical complications. Patients will be followed in the nationwide metabolic surgery register SOReg, the national inpatient register, national cause of death register, the Swedish prescribed drug register, and the Swedish population register. If positive results these can be included in guidelines for MBS.

Decisions about adoption of medical treatments by the healthcare system require precise quantification of their effectiveness. However, the findings from randomized trials may not be applicable to the general population of individuals who may benefit from the treatments. A treatment that works well on average in the selected participants in randomized trials may have a lower effectiveness in the typical patients, with a different distribution of socioeconomic and clinical factors, who will use the treatment in the real world. This reduction in effectiveness needs to be known and quantified so that it can guide policy decisions. Yet the task of extending randomized trial results to the general population of patients is often handled via informal subjective assessments.In contrast, we propose to develop, refine, and implement methodology to extend causal inferences from randomized trials to the general population of patients who may benefit from the treatments. This project will use real world data from the SWEDEHEART registry and linked nationwide registers, along with data from two randomized trials: TASTE and VALIDATE.  We will develop two use cases in cardiovascular research and build the tools that can later be applied to any other medical intervention. Specifically, we estimate the effect of routine thrombus aspiration before percutaneous coronary intervention in the whole trial-eligible population of Sweden, estimate the effect of two anticoagulant medications during percutaneous coronary intervention in the whole trial-eligible population of Sweden, and create tutorials, teaching materials, and open-source code to facilitate the uptake of this methodology by Swedish researchers. Our research will improve public health decisions in Sweden and will serve as a model for other countries interested in the extension of findings from randomized trials to their general population of patients who can benefit from the treatments under study.

Meta-analysis confirm the benefits of supervised exercise-based cardiac rehabilitation (exCR) in terms of marked reductions in cardiac mortality with 26% and hospital readmission with 31% in patients with myocardial infarction (MI). Despite evidence-based benefits, adherence with traditional centre-based exCR remains low. Remote video exCR combines the accessibility of home-based exCR programs with the specialist monitoring of center-based exCR, by connecting the physiotherapist at hospital with several patients exercising at home.Our primary aim is to evaluate if remote video exCR, offered as an alternative to centre-based exCR, could increase the proportion of patients with MI successfully completing exCR. Secondary aims are to investigate if remote video exCR is as least as effective as centre-based exCR, in terms of physical fitness, patient-reported outcome measures and cost-effectiveness. Follow-up of cardiovascular events will be performed after 1 and 3 years. In a national registry-based crossover clinical trial (RRCT), 1500 patients with MI at 33 exCR centers will be randomized in clusters to intervention or control. Patients at intervention centers will be offered remote video exCR or centre-based exCR, as self-preferred choice. At control centers, patients will be offered centre-based exCR, only. After one year cross-over will occur. The SWEDEHEART registry will be used for data collection and for follow-up.Using a RRCT design a large cohort of patients with MI can be included to a low cost. The study provides a unique opportunity to evaluate effects of an evidence-based treatment, currently performed at hospitals, in a new model of care using new technology. Through the possibilities of digitisation, accessibility to exCR can be increased, providing a more equal access to health care across the country, with significant effects for the individual as well as for society.