Dapagliflozin in Myocardial Infarction without Diabetes or Heart Failure.

BACKGROUND: In patients with acute myocardial infarction (MI), therapies that could further reduce the risk of adverse cardiovascular and metabolic outcomes are needed. METHODS: In this international registry-based, randomized, double-blind trial, patients without prior diabetes or chronic heart failure, presenting with acute MI and impaired left ventricular systolic function, were randomly assigned 10 mg of dapagliflozin or placebo, given once daily. The primary outcome was the hierarchical composite of death, hospitalization for heart failure, nonfatal MI, atrial fibrillation/flutter, type 2 diabetes mellitus, New York Heart Association Functional Classification at the last visit, and body weight decrease of 5% or greater at the last visit using the win ratio analysis method. The key secondary outcome was the same hierarchical composite excluding the body weight component. RESULTS: We enrolled 4017 patients of whom 2019 were assigned to dapagliflozin and 1998 to placebo. The analysis of the primary hierarchical composite outcome resulted in significantly more wins for dapagliflozin than for placebo (win ratio, 1.34; 95% confidence interval [CI], 1.20 to 1.50; P<0.001). The win ratio outcome, which was adopted in a change of analysis during trial performance because of low event accrual, was mainly driven by the added cardiometabolic outcomes. The composite of time to cardiovascular death/hospitalization for heart failure occurred in 50/2019 (2.5%) patients assigned to dapagliflozin and 52/1998 (2.6%) patients assigned to placebo (hazard ratio, 0.95; 95% CI, 0.64 to 1.40). The rates of other cardiovascular events were low, with differences between the groups not reaching nominal statistical significance. No safety concerns were identified. CONCLUSIONS: In patients with acute MI as noted above, after approximately 1 year of treatment with dapagliflozin there were significant benefits with regard to improvement in cardiometabolic outcomes but no impact on the composite of cardiovascular death or hospitalization for heart failure compared with placebo. (Funded by AstraZeneca; ClinicalTrial.gov number, NCT04564742.)

Postdischarge major bleeding, myocardial infarction, and mortality risk after coronary artery bypass grafting.

OBJECTIVE: To investigate the incidence and mortality risk associated with postdischarge major bleeding after coronary artery bypass grafting (CABG), and relate this to the incidence of, and mortality risk from, postdischarge myocardial infarction. METHODS: All patients undergoing first-time isolated CABG in Sweden in 2006-2017 and surviving 14 days after hospital discharge were included in a cohort study. Individual patient data from the SWEDEHEART Registry and five other mandatory nationwide registries were merged. Piecewise Cox proportional hazards models were used to investigate associations between major bleeding, defined as hospitalisation for bleeding, with subsequent mortality risk. Similar Cox proportional hazards models were used to investigate the association between postdischarge myocardial infarction and mortality risk. RESULTS: Among 36 633 patients, 2429 (6.6%) had a major bleeding event and 2231 (6.1%) had a myocardial infarction. Median follow-up was 6.0 (range 0-11) years. Major bleeding was associated with higher mortality risk <30 days (adjusted HR (aHR)=20.2 (95% CI 17.3 to 23.5)), 30-365 days (aHR=3.8 (95% CI 3.4 to 4.3)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event. Myocardial infarction was associated with higher mortality risk <30 days (aHR=20.0 (95% CI 16.7 to 23.8)), 30-365 days (aHR=4.1 (95% CI 3.6 to 4.8)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event. CONCLUSIONS: The increase in mortality risk associated with a postdischarge major bleeding after CABG is substantial and is similar to the mortality risk associated with a postdischarge myocardial infarction.

Outcomes in patients with chest pain in emergency departments using high-sensitivity versus conventional troponins.

Objectives. There is a paucity of data regarding the association between the use of high-sensitivity troponin (hs-cTn) compared with conventional troponin (cTn) and outcomes in chest pain patients in emergency departments (EDs). This study examined the impact of hs-cTnT on prognosis in chest pain patients in EDs. Design. In an observational cohort study, we included chest pain patients visiting the EDs of 14 hospitals in Sweden from 2011 to 2016. The study population was retrieved from each hospital, and information on characteristics and outcomes was collected from nationwide registries. Cox regression was used to estimate adjusted hazard ratios with 95% confidence intervals (HR, 95% CI) for (1) 1-year all-cause mortality, (2) missed acute coronary syndromes (ACSs), (3) use of coronary angiography, and (4) revascularizations within 30 days. Results. We included 170461 patients with chest pain where 62669 patients were tested with cTn while 107792 patients were tested with hs-cTnT. We found 4149 (4.6%) deaths in the cTn group and 6087 (3.7%) deaths in the hs-cTnT group. Patients in the hs-cTnT group had 9% lower mortality (0.91, 0.87-0.94), and were 14% more likely to undergo coronary angiography (1.14, 1.10-1.17), and 12% more likely to be revascularized (1.12, 1.08-1.17) than patients in the cTn group. Conclusions. Patients with chest pain visiting EDs using hs-cTnT had lower mortality and a higher likelihood of undergoing coronary angiographies and revascularizations than those using cTn. There may be a survival benefit of being tested with hs-cTnT compared with cTn in patients seeking medical attention for chest pain.

Comparison of Midterm Outcomes Associated With Aspirin and Ticagrelor vs Aspirin Monotherapy After Coronary Artery Bypass Grafting for Acute Coronary Syndrome.

Importance: Guidelines recommend dual antiplatelet therapy after coronary artery bypass grafting (CABG) for patients with acute coronary syndrome (ACS). However, the evidence for these recommendations is weak. Objective: To compare midterm outcomes after CABG in patients with ACS treated postoperatively with acetylsalicylic acid (ASA) and ticagrelor or with ASA monotherapy. Design, Setting, and Participants: This cohort study used merged data from several national registries of Swedish patients who were diagnosed with ACS and subsequently underwent CABG. All included patients underwent isolated CABG in Sweden between 2012 and 2017 with an ACS diagnosis less than 6 weeks before the procedure, survived 14 days after discharge from hospital, and were treated postoperatively with ASA plus ticagrelor or ASA monotherapy. A multivariable Cox regression model was used for the main analysis, and propensity score-matched models were performed as sensitivity analysis. Data were analyzed between May and September 2020. Exposures: Postoperative antiplatelet treatment, defined as filled prescriptions, with either ASA and ticagrelor or ASA only. Main Outcomes and Measures: Major adverse cardiovascular events (MACE), defined as all-cause mortality, myocardial infarction, and stroke, and major bleeding, at 12 months and at the end of follow-up. Results: A total of 6558 patients (5281 [80.5%] men; mean [SD] age at surgery, 67.6 [9.3] years) were included; 1813 (27.6%) were treated with ASA plus ticagrelor and 4745 (72.4%) were treated with ASA monotherapy. Crude MACE rate was 3.0 per 100 person years (95% CI, 2.5-3.6 per 100 person years) in the ASA plus ticagrelor group and 3.8 per 100 person years (95% CI, 3.5-4.1 per 100 person years) in the ASA group. After adjustment, there was no significant difference in MACE risk between ASA plus ticagrelor vs ASA only, neither during the first 12 months (adjusted hazard ratio [aHR], 0.84; 95% CI, 0.58-1.21; P = .34) or during total follow-up (aHR, 0.89; 95% CI, 0.71-1.11; P = .29). The use of ASA plus ticagrelor was associated with a significantly increased risk for major bleeding during the first 12 months (aHR, 1.90; 95% CI, 1.16-3.13; P = .011). Sensitivity analyses confirmed the results. Conclusions and Relevance: In patients with ACS who survived 2 weeks after CABG, no significant difference in the risk of death or ischemic events could be demonstrated between ASA plus ticagrelor and patients treated with ASA only, while the risk for major bleeding was higher in patients treated with ASA plus ticagrelor. Sufficiently powered prospective randomized trials comparing different antiplatelet therapy strategies after CABG are warranted.

[Q fever endocarditis - a rare condition with high mortality]. / Q-feberendokardit ­ en ovanlig åkomma med hög mortalitet.

Coxiella burnetii is the causative agent of Q fever. It can manifest in both acute and chronic forms. Culture-negative endocarditis is the most common and serious presenting form of chronic Q fever. This occurs almost exclusively in patients with a pre-existing valvulopathy including valve prosthesis or immunocompromised patients as well as in pregnant women. Diagnosis is often delayed or missed due to the nonspecific symptoms of the condition. Without the proper antimicrobial therapy, the mortality is high. Q fever endocarditis should be suspected especially in people who recently had acute Q fever, people who come from endemic areas as well as people with occupational contact with sheep, goats and cattle and endocarditis symptoms. In this article we present a case with a patient who died of unknown cause and where PCR performed on autopsy of the valve revealed Q fever endocarditis.

Secondary prevention medications after coronary artery bypass grafting and long-term survival: a population-based longitudinal study from the SWEDEHEART registry.

AIMS: To evaluate the long-term use of secondary prevention medications [statins, ß-blockers, renin-angiotensin-aldosterone system (RAAS) inhibitors, and platelet inhibitors] after coronary artery bypass grafting (CABG) and the association between medication use and mortality. METHODS AND RESULTS: All patients who underwent isolated CABG in Sweden from 2006 to 2015 and survived at least 6 months after discharge were included (n = 28 812). Individual patient data from SWEDEHEART and other mandatory nationwide registries were merged. Multivariable Cox regression models using time-updated data on dispensed prescriptions were used to assess associations between medication use and long-term mortality. Statins were dispensed to 93.9% of the patients 6 months after discharge and to 77.3% 8 years later. Corresponding figures for ß-blockers were 91.0% and 76.4%, for RAAS inhibitors 72.9% and 65.9%, and for platelet inhibitors 93.0% and 79.8%. All medications were dispensed less often to patients ≥75 years. Treatment with statins [hazard ratio (HR) 0.56, 95% confidence interval (95% CI) 0.52-0.60], RAAS inhibitors (HR 0.78, 95% CI 0.73-0.84), and platelet inhibitors (HR 0.74, 95% CI 0.69-0.81) were individually associated with lower mortality risk after adjustment for age, gender, comorbidities, and use of other secondary preventive drugs (all P < 0.001). There was no association between ß-blockers and mortality risk (HR 0.97, 95% CI 0.90-1.06; P = 0.54). CONCLUSION: The use of secondary prevention medications after CABG was high early after surgery but decreased significantly over time. The results of this observational study, with inherent risk of selection bias, suggest that treatment with statins, RAAS inhibitors, and platelet inhibitors is essential after CABG whereas the routine use of ß-blockers may be questioned.

High-Sensitivity Troponins and Outcomes After Myocardial Infarction.

BACKGROUND: It remains unknown how the introduction of high-sensitivity cardiac troponin T (hs-cTnT) has affected the incidence, prognosis, and use of coronary angiographies and revascularizations in patients with myocardial infarction (MI). OBJECTIVES: The aim of this study was to investigate how the incidence of MI and prognosis after a first MI was affected by the introduction of hs-cTnT. METHODS: In a cohort study, the authors included all patients with a first MI from the Swedish National Patient Registry from 2009 to 2013. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for risk of all-cause mortality, reinfarction, coronary angiographies, and revascularizations in patients with MI diagnosed using hs-cTnT compared with those diagnosed using conventional troponins (cTn). RESULTS: During the study period, 47,133 MIs were diagnosed using cTn and 40,746 using hs-cTnT. The rate of MI increased by 5% (95% CI: 0% to 10%) after the introduction of hs-cTnT. During 3.9 ± 2.8 years of follow-up, there were 33,492 deaths, with no difference in the risk of all-cause mortality (adjusted HR: 1.00; 95% CI: 0.97 to 1.02). There were, in total, 15,766 reinfarctions during 3.1 ± 2.3 years of follow-up, with the risk of reinfarction reduced by 11% in patients diagnosed using hs-cTnT (adjusted HR: 0.89; 95% CI: 0.86 to 0.91). The use of coronary angiographies (adjusted HR: 1.16; 95% CI: 1.14 to 1.18) and revascularizations (adjusted HR: 1.13; 95% CI: 1.11 to 1.15) increased in the hs-cTnT group. CONCLUSIONS: In a nationwide cohort study including 87,879 patients with a first MI, the introduction of hs-cTnT was associated with an increased incidence of MI, although with no impact on survival. We also found a reduced risk of reinfarction alongside increased use of coronary angiographies and revascularizations.

Patients expectations and fulfilment of expectations before and after treatment for suspected coronary artery disease assessed with a newly developed questionnaire in combination with established health-related quality of life questionnaires.

BACKGROUND: Clinical decision-making is often based on evidence of outcome after a specific treatment. Healthcare providers and patients may, however, have different perceptions and expectations of what to achieve from a certain healthcare measure. AIMS: To evaluate patients' expectations, perceptions and health related quality of life (HRQoL) before a care process including coronary angiography for suspected coronary artery disease and to evaluate the fulfilment of these expectations in relation to established patient reported outcome measures (PROMs) 6 months later. Furthermore, an aim was to try to define meaningful patient reported experience measures (PREMs) in this population. METHODS: 544 patients planned for coronary angiography completed a newly developed questionnaire to assess expectations and perceptions of treatment, the expectation questionnaire (ExpQ) and two established HRQoL questionnaires together with the established generic Short-Form 36 (SF36) and the disease specific Seattle Angina Questionnaire (SAQ). RESULTS: Patients had before the intervention, in general, high expectations of improvement after investigation and treatment and there was a positive attitude towards life style changes, medication and participation in decision-making regarding their own treatment. Only, 56.4% of the patients, however, reported fulfilment of treatment expectations. Fulfilment of treatment expectations correlated strongly with improvement in HRQoL after the care process. CONCLUSIONS: To measure patients ´ expectations and fulfilments of these may offer simple and meaningful outcomes to evaluate a healthcare process from a patient ´s perspective. To approach patients' expectations may also strengthen patient involvement in the care process with the possibilities of both higher patient satisfaction and medical results of the treatment.

Trends in Gender Differences in Cardiac Care and Outcome After Acute Myocardial Infarction in Western Sweden: A Report From the Swedish Web System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART).

BACKGROUND: Cardiovascular disease is the most common cause of death for both genders. Debates are ongoing as to whether gender-specific differences in clinical course, diagnosis, and management of acute myocardial infarction (MI) exist. METHODS AND RESULTS: We compared all men and women who were treated for acute MI at cardiac care units in Västra Götaland, Sweden, between January 1995 and October 2014 by obtaining data from the prospective SWEDEHEART (Swedish Web-System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry. We performed unadjusted and adjusted Cox proportional hazards and logistic regression analyses on complete case data and on imputed data sets. Overall, 48 118 patients (35.4% women) were diagnosed with acute MI. Women as a group had better age-adjusted prognosis than men, but this survival benefit was absent for younger women (aged <60 years) and for women with ST-segment elevation MI. Compared with men, younger women and women with ST-segment elevation MI were more likely to develop prehospital cardiogenic shock (adjusted odds ratio 1.67, 95% CI 1.30 to 2.16, P<0.001 and adjusted odds ratio 1.31, 95% CI 1.16 to 1.48, P<0.001) and were less likely to be prescribed evidence-based treatment at discharge (P<0.001 for ß-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, statins, and P2Y12 antagonists). Differences in treatment between the genders did not decrease over the study period (P>0.1 for all treatments). CONCLUSIONS: Women on average have better adjusted prognosis than men after acute MI; however, younger women and women with ST-segment elevation MI have disproportionately poor prognosis and are less likely to be prescribed evidence-based treatment.

Clinical decision support system (CDSS)--effects on care quality.

PURPOSE: Despite their efficacy, some recommended therapies are underused. The purpose of this paper is to describe clinical decision support system (CDSS) development and its impact on clinical guideline adherence. DESIGN/METHODOLOGY/APPROACH: A new CDSS was developed and introduced in a cardiac intensive care unit (CICU) in 2003, which provided physicians with patient-tailored reminders and permitted data export from electronic patient records into a national quality registry. To evaluate CDSS effects in the CICU, process indicators were compared to a control group using registry data. All CICUs were in the same region and only patients with acute coronary syndrome were included. FINDINGS: CDSS introduction was associated with increases in guideline adherence, which ranged from 16 to 35 per cent, depending on the therapy. Statistically significant associations between guideline adherence and CDSS use remained over the five-year period after its introduction. During the same period, no relapses occurred in the intervention CICU. PRACTICAL IMPLICATIONS: Guideline adherence and healthcare quality can be enhanced using CDSS. This study suggests that practitioners should turn to CDSS to improve healthcare quality. ORIGINALITY/VALUE: This paper describes and evaluates an intervention that successfully increased guideline adherence, which improved healthcare quality when the intervention CICU was compared to the control group.

Sleep, arousal and health-related quality of life in men and women with coronary artery disease.

AIM: To evaluate whether there are gender differences in insomnia, sleep quality, sleep efficiency (%), general arousal, disease-specific and health-related quality of life in patients with coronary artery disease, compared with an age- and gender-matched randomly selected group from the general population. BACKGROUND: There are gender difference effects of sleep disturbances in the general population, but this perspective among patients with coronary artery disease has been poorly analysed. DESIGN: In this prospective study, comparative, descriptive and model testing designs were used. METHOD: The patients with coronary artery disease, 556 men and 324 women aged 25-86, were compared with a matched population-based group. Data were collected by validated and reliability-tested questionnaires. RESULTS: The prevalence of severe insomnia varied between 17-44% in all four groups. The severe insomniac coronary artery disease patients displayed a two- or threefold higher presleep arousal, had two hours shorter nocturnal sleep duration/night and were more limited in their physical exercise level than the population-based group. Gender differences in sleep quality, sleep efficiency (%) and general arousal disappeared with increased insomnia severity. CONCLUSIONS: Independent of gender, age and comorbidity, physical exercise, general arousal behaviour and delayed poststress recovery after mental stress were found to have a negative impact on the coronary artery disease patients' sleep quality and sleep efficiency (%), interfering with their health-related quality of life. The variables significantly explained 41% of the sleep quality outcome and 29% of the sleep efficiency (%). RELEVANCE TO CLINICAL PRACTICE: Insomnia because of hyperarousal behaviour can be an important factor in the development of an individual self-care management programme supported by a healthcare team.

Heart rate variability in premenstrual dysphoric disorder.

Measuring heart rate variability (HRV) is a way to assess the autonomic regulation of the heart. Decreased HRV, indicating reduced parasympathetic tone, has previously been found in depression and anxiety disorders. The objective of this study was to assess HRV in women with premenstrual dysphoric disorder (PMDD). To this end, time domain variables and frequency domain variables were assessed in 28 women with PMDD and in 11 symptom-free controls during both the symptomatic luteal phase and the non-symptomatic follicular phase of the menstrual cycle. Two variables reflecting vagal activity in the time domain, the root mean square of differences of successive normal RR intervals (rMSSD) and standard deviation of normal RR intervals (SDNN) were lower in PMDD patients, but this difference was statistically significant in the follicular phase only. The most important vagal measure in the frequency domain, supine high frequency (HF), also appeared lower in PMDD subjects during the follicular phase. It is suggested that PMDD may be associated with reduced vagal tone compared to controls and that this difference is most apparent in the non-symptomatic follicular phase of the menstrual cycle.