Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction.

BACKGROUND: Most trials that have shown a benefit of beta-blocker treatment after myocardial infarction included patients with large myocardial infarctions and were conducted in an era before modern biomarker-based diagnosis of myocardial infarction and treatment with percutaneous coronary intervention, antithrombotic agents, high-intensity statins, and renin-angiotensin-aldosterone system antagonists. METHODS: In a parallel-group, open-label trial performed at 45 centers in Sweden, Estonia, and New Zealand, we randomly assigned patients with an acute myocardial infarction who had undergone coronary angiography and had a left ventricular ejection fraction of at least 50% to receive either long-term treatment with a beta-blocker (metoprolol or bisoprolol) or no beta-blocker treatment. The primary end point was a composite of death from any cause or new myocardial infarction. RESULTS: From September 2017 through May 2023, a total of 5020 patients were enrolled (95.4% of whom were from Sweden). The median follow-up was 3.5 years (interquartile range, 2.2 to 4.7). A primary end-point event occurred in 199 of 2508 patients (7.9%) in the beta-blocker group and in 208 of 2512 patients (8.3%) in the no-beta-blocker group (hazard ratio, 0.96; 95% confidence interval, 0.79 to 1.16; P = 0.64). Beta-blocker treatment did not appear to lead to a lower cumulative incidence of the secondary end points (death from any cause, 3.9% in the beta-blocker group and 4.1% in the no-beta-blocker group; death from cardiovascular causes, 1.5% and 1.3%, respectively; myocardial infarction, 4.5% and 4.7%; hospitalization for atrial fibrillation, 1.1% and 1.4%; and hospitalization for heart failure, 0.8% and 0.9%). With regard to safety end points, hospitalization for bradycardia, second- or third-degree atrioventricular block, hypotension, syncope, or implantation of a pacemaker occurred in 3.4% of the patients in the beta-blocker group and in 3.2% of those in the no-beta-blocker group; hospitalization for asthma or chronic obstructive pulmonary disease in 0.6% and 0.6%, respectively; and hospitalization for stroke in 1.4% and 1.8%. CONCLUSIONS: Among patients with acute myocardial infarction who underwent early coronary angiography and had a preserved left ventricular ejection fraction (≥50%), long-term beta-blocker treatment did not lead to a lower risk of the composite primary end point of death from any cause or new myocardial infarction than no beta-blocker use. (Funded by the Swedish Research Council and others; REDUCE-AMI ClinicalTrials.gov number, NCT03278509.).

Prospective benchmarking of an observational analysis in the SWEDEHEART registry against the REDUCE-AMI randomized trial.

Prospective benchmarking of an observational analysis against a randomized trial increases confidence in the benchmarking process as it relies exclusively on aligning the protocol of the trial and the observational analysis, while the trials findings are unavailable. The Randomized Evaluation of Decreased Usage of Betablockers After Myocardial Infarction (REDUCE-AMI, ClinicalTrials.gov ID: NCT03278509) trial started recruitment in September 2017 and results are expected in 2024. REDUCE-AMI aimed to estimate the effect of long-term use of beta blockers on the risk of death and myocardial following a myocardial infarction with preserved left ventricular systolic ejection fraction. We specified the protocol of a target trial as similar as possible to that of REDUCE-AMI, then emulated the target trial using observational data from Swedish healthcare registries. Had everyone followed the treatment strategy as specified in the target trial protocol, the observational analysis estimated a reduction in the 5-year risk of death or myocardial infarction of 0.8 percentage points for beta blockers compared with no beta blockers; effects ranging from an absolute reduction of 4.5 percentage points to an increase of 2.8 percentage points in the risk of death or myocardial infarction were compatible with our data under conventional statistical criteria. Once results of REDUCE-AMI are published, we will compare the results of our observational analysis against those from the trial. If this prospective benchmarking is successful, it supports the credibility of additional analyses using these observational data, which can rapidly deliver answers to questions that could not be answered by the initial trial. If benchmarking proves unsuccessful, we will conduct a "postmortem" analysis to identify the reasons for the discrepancy. Prospective benchmarking shifts the investigator focus away from an endeavour to use observational data to obtain similar results as a completed randomized trial, to a systematic attempt to align the design and analysis of the trial and the observational analysis.

A study of size-selective renal elimination using a novel human model.

The recently discovered selective glomerular hypofiltration syndromes have increased interest in the actual elimination of molecules in the human kidney. In the present study, a novel human model was introduced to directly measure the single-pass renal elimination of molecules of increasing size. Plasma concentrations of urea, creatinine, C-peptide, insulin, pro-BNP, ß2-microglobulin, cystatin C, troponin-T, orosomucoid, albumin, and IgG were analysed in arterial and renal venous blood from 45 patients undergoing Transcatheter Aortic Valve Implantation (TAVI). The renal elimination ratio (RER) was calculated as the arteriovenous concentration difference divided by the arterial concentration. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI equations for both creatinine and cystatin C. Creatinine (0.11 kDa) showed the highest RER (21.0 ± 6.3%). With increasing molecular size, the RER gradually decreased, where the RER of cystatin C (13 kDa) was 14.4 ± 5.3% and troponin-T (36 kDa) was 11.3 ± 4.6%. The renal elimination threshold was found between 36 and 44 kDa as the RER of orosomucoid (44 kDa) was -0.2 ± 4.7%. The RER of creatinine and cystatin C showed a significant and moderate positive linear relationship with eGFR (r = 0.48 and 0.40). In conclusion, a novel human model was employed to demonstrate a decline in renal elimination with increasing molecular size. Moreover, RERs of creatinine and cystatin C were found to correlate with eGFR, suggesting the potential of this model to study selective glomerular hypofiltration syndromes.

Temporal trends in bleeding events in acute myocardial infarction: insights from the SWEDEHEART registry.

AIMS: To describe the time trends of in-hospital and out-of-hospital bleeding parallel to the development of new treatments and ischaemic outcomes over the last 20 years in a nationwide myocardial infarction (MI) population. METHODS AND RESULTS: Patients with acute MI (n = 371 431) enrolled in the SWEDEHEART registry from 1995 until May 2018 were selected and evaluated for in-hospital bleeding and out-of-hospital bleeding events at 1 year. In-hospital bleeding increased from 0.5% to a peak at 2% 2005/2006 and thereafter slightly decreased to a new plateau around 1.3% by the end of the study period. Out-of-hospital bleeding increased in a stepwise fashion from 2.5% to 3.5 % in the middle of the study period and to 4.8% at the end of the study period. The increase in both in-hospital and out-of-hospital bleeding was parallel to increasing use of invasive strategy and adjunctive antithrombotic treatment, dual antiplatelet therapy (DAPT), and potent DAPT, while the decrease in in-hospital bleeding from 2007 to 2010 was parallel to implementation of bleeding avoidance strategies. In-hospital re-infarction decreased from 2.8% to 0.6% and out-of-hospital MI decreased from 12.6% to 7.1%. The composite out-of-hospital MI, cardiovascular death, and stroke decreased in a similar fashion from 18.4% to 9.1%. CONCLUSION: During the last 20 years, the introduction of invasive and more intense antithrombotic treatment has been associated with an increase in bleeding events but concomitant there has been a substantial greater reduction of ischaemic events including improved survival.

Diagnostic accuracy of troponin T measured ≥6h after symptom onset for ruling out myocardial infarction.

Objectives: Guidelines recommend a single high-sensitivity cardiac troponin T (hs-cTnT) ≤14 ng/L measured ≥6 h after chest pain onset combined with a GRACE score <140 and the patient being pain-free for ruling out myocardial infarction (MI). There is however little data on the performance of this strategy. We therefore aimed to evaluate the diagnostic accuracy of a hs-cTnT ≤14 ng/L measured ≥6 h after chest pain onset when combined with GRACE score or other clinical risk stratification tools. Design: This was a secondary analysis of a prospective observational study, which enrolled emergency department (ED) chest pain patients. The hs-cTnT strategy was combined with HEART, TIMI, EDACS, GRACE score and ED physician's overall assessment of patient history and ECG. The primary outcome was MI, and the secondary outcome was 30-day major adverse cardiac events (MACE). Results: All tested diagnostic strategies were shown to have a negative predictive value (NPV) ≥99.5% for ruling out MI. Using HEART, TIMI, EDACS or ECG + patient history also resulted in a NPV ≥98% for ruling out 30-day MACE. An isolated hs-cTnT ≤14 ng/L measured ≥6 h after chest pain onset and the combination with GRACE score both had a NPV <98% for ruling out 30-day MACE. Conclusion: A single hs-cTnT ≤14 ng/L obtained ≥6 h from chest pain onset, with and without GRACE score, reliably ruled out MI but did not perform well for ruling out 30-day MACE. These results question current guideline recommendations, and indicate that HEART, EDACS, TIMI, or ECG + patient history strategies should be the preferred risk stratification tools.

Inhibition of pro-inflammatory myeloid cell responses by short-term S100A9 blockade improves cardiac function after myocardial infarction.

AIMS: Neutrophils have both detrimental and beneficial effects in myocardial infarction (MI), but little is known about the underlying pathways. S100A8/A9 is a pro-inflammatory alarmin abundantly expressed in neutrophils that is rapidly released in the myocardium and circulation after myocardial ischaemia. We investigated the role of S100A8/A9 in the innate immune response to MI. METHODS AND RESULTS: In 524 patients with acute coronary syndrome (ACS), we found that high plasma S100A8/A9 at the time of the acute event was associated with lower left ventricular ejection fraction (EF) at 1-year and increased hospitalization for heart failure (HF) during follow-up. In wild-type C57BL/6 mice with MI induced by permanent coronary artery ligation, treatment with the S100A9 blocker ABR-238901 during the inflammatory phase of the immune response inhibited haematopoietic stem cell proliferation and myeloid cell egression from the bone marrow. The treatment reduced the numbers of neutrophils and monocytes/macrophages in the myocardium, promoted an anti-inflammatory environment, and significantly improved cardiac function compared with MI controls. To mimic the clinical scenario, we further confirmed the effects of the treatment in a mouse model of ischaemia/reperfusion. Compared with untreated mice, 3-day ABR-238901 treatment significantly improved left ventricular EF (48% vs. 35%, P = 0.002) and cardiac output (15.7 vs. 11.1 mL/min, P = 0.002) by Day 21 post-MI. CONCLUSION: Short-term S100A9 blockade inhibits inflammation and improves cardiac function in murine models of MI. As an excessive S100A8/A9 release is linked to incident HF, S100A9 blockade might represent a feasible strategy to improve prognosis in ACS patients.

Long-Term Effects of Oxygen Therapy on Death or Hospitalization for Heart Failure in Patients With Suspected Acute Myocardial Infarction

Background: In the DETO2X-AMI trial (Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction), we compared supplemental oxygen with ambient air in normoxemic patients presenting with suspected myocardial infarction and found no significant survival benefit at 1 year. However, important secondary end points were not yet available. We now report the prespecified secondary end points cardiovascular death and the composite of all-cause death and hospitalization for heart failure. Methods: In this pragmatic, registry-based randomized clinical trial, we used a nationwide quality registry for coronary care for trial procedures and evaluated end points through the Swedish population registry (mortality), the Swedish inpatient registry (heart failure), and cause of death registry (cardiovascular death). Patients with suspected acute myocardial infarction and oxygen saturation of ≥90% were randomly assigned to receive either supplemental oxygen at 6 L/min for 6 to 12 hours delivered by open face mask or ambient air. Results: A total of 6629 patients were enrolled. Acute heart failure treatment, left ventricular systolic function assessed by echocardiography, and infarct size measured by high-sensitive cardiac troponin T were similar in the 2 groups during the hospitalization period. All-cause death or hospitalization for heart failure within 1 year after randomization occurred in 8.0% of patients assigned to oxygen and in 7.9% of patients assigned to ambient air (hazard ratio, 0.99; 95% CI, 0.84­1.18; P=0.92). During long-term follow-up (median [range], 2.1 [1.0­3.7] years), the composite end point occurred in 11.2% of patients assigned to oxygen and in 10.8% of patients assigned to ambient air (hazard ratio, 1.02; 95% CI, 0.88­1.17; P=0.84), and cardiovascular death occurred in 5.2% of patients assigned to oxygen and in 4.8% assigned to ambient air (hazard ratio, 1.07; 95% CI, 0.87­1.33; P=0.52). The results were consistent across all predefined subgroups. Conclusions: Routine use of supplemental oxygen in normoxemic patients with suspected myocardial infarction was not found to reduce the composite of all-cause mortality and hospitalization for heart failure, or cardiovascular death within 1 year or during long-term follow-up. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01787110.

Elevated IL-27 in patients with acute coronary syndrome is associated with adverse ventricular remodeling and increased risk of recurrent myocardial infarction and cardiovascular death.

BACKGROUND AND AIMS: IL-27 is an immunoregulatory cytokine belonging to the IL-6/IL-12 family that was found to be elevated in acute coronary syndrome (ACS) patients. We investigated whether IL-27 is related to post-ischemic cardiac remodeling and long-term prognosis in this patient group. METHODS: We included 524 ACS patients, defined as acute myocardial infarction (AMI) or unstable angina (UA). A subgroup of 107 patients donated blood samples 6 weeks after the index event, and underwent a follow-up echocardiographical examination at 1 year. We measured plasma levels of IL-27, high sensitivity troponin T (hsTNT), C-reactive protein (hsCRP) and cystatin C at baseline and in the 6-week samples. The median follow-up period of the cohort was 2.2 years. RESULTS: The incidence of the combined end-point of AMI and cardiovascular death was higher in patients with plasma IL-27 within the top two tertiles both at baseline and after 6 weeks. After correction for cardiovascular risk factors, medication, hsTNT, hsCRP, and eGFR, patients with baseline IL-27 levels within the highest tertile had a significantly elevated risk for the combined end-point compared with the lowest tertile (hazard ratio 2.70, 95% CI 1.06-6.90, p = .038). Additionally, higher baseline IL-27 levels were associated with deleterious left ventricular remodeling and deterioration of systolic and diastolic function during the first year of follow-up. CONCLUSIONS: Elevated IL-27 at the time of an ACS is independently related to impaired cardiac function and worse long-term prognosis. Our data warrants further mechanistic studies to elucidate the involvement of IL-27 in cardiac repair and remodeling after ACS.

Relations between implementation of new treatments and improved outcomes in patients with non-ST-elevation myocardial infarction during the last 20 years: experiences from SWEDEHEART registry 1995 to 2014.

Aims: We assessed the changes in short- and long-term outcomes and their relation to implementation of new evidence-based treatments in all patients with non-ST-elevation myocardial infarction (NSTEMI) in Sweden over 20 years. Methods and results: Cases with NSTEMI (n = 205 693) between 1995 and 2014 were included from the nationwide Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry. During 20 years in-hospital invasive procedures increased from 1.9% to 73.2%, percutaneous coronary intervention or coronary artery bypass grafting 6.5% to 58.1%, dual antiplatelet medication 0% to 72.7%, statins 13.3% to 85.6%, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blocker 36.8% to 75.5%. The standardized 1-year mortality ratio compared with a control population decreased from 5.53 [95% confidence interval (CI) 5.30-5.75] to 3.03 (95% CI 2.89-3.19). If patients admitted the first 2 years were modelled to receive the same invasive treatments as the last 2 years the expected mortality/myocardial infarction (MI) rate would be reduced from 33.0% to 25.0%. After adjusting for differences in baseline characteristics, the change of 1-year cardiovascular death/MI corresponded to a linearly decreasing odds ratio trend of 0.930 (95% CI 0.926-0.935) per 2-year period. This trend was substantially attenuated [0.970 (95% CI 0.964-0.975)] after adjusting for changes in coronary interventions, and almost eliminated [0.988 (95% CI 0.982-0.994)] after also adjusting for changes in discharge medications. Conclusion: In NSTEMI patients during the last 20 years, there has been a substantial improvement in long-term survival and reduction in the risk of new cardiovascular events. These improvements seem mainly explained by the gradual uptake and widespread use of in-hospital coronary interventions and evidence-based long-term medications.

Improved outcomes in patients with ST-elevation myocardial infarction during the last 20 years are related to implementation of evidence-based treatments: experiences from the SWEDEHEART registry 1995-2014.

AIMS: Impact of changes of treatments on outcomes in ST-elevation myocardial infarction (STEMI) patients in real-life health care has not been documented. METHODS AND RESULTS: All STEMI cases (n = 105.674) registered in the nation-wide SWEDEHEART registry between 1995 and 2014 were included and followed for fatal and non-fatal outcomes for up to 20 years. Most changes in treatment and outcomes occurred from 1994 to 2008. Evidence-based treatments increased: reperfusion from 66.2 to 81.7%; primary percutaneous coronary intervention: 4.5 to 78.0%; dual antiplatelet therapy from 0 to 89.6%; statin: 14.1 to 93.6%; beta-blocker: 78.2 to 91.0%, and angiotensin-converting-enzyme/angiotensin-2-receptor inhibitors: 40.8 to 85.2% (P-value for-trend <0.001 for all). One-year mortality decreased from 22.1 to 14.1%. Standardized incidence ratio compared with the general population decreased from 5.54 to 3.74 (P < 0.001). Cardiovascular (CV) death decreased from 20.1 to 11.1%, myocardial infarction (MI) from 11.5 to 5.8%; stroke from 2.9 to 2.1%; heart failure from 7.1 to 6.2%. After standardization for differences in demography and baseline characteristics, the change of 1-year CV-death or MI corresponded to a linear trend of 0.915 (95% confidence interval: 0.906-0.923) per 2-year period which no longer was significant, 0.997 (0.984-1.009), after adjustment for changes in treatment. The changes in treatment and outcomes were most pronounced from 1994 to 2008. CONCLUSION: Gradual implementation of new and established evidence-based treatments in STEMI patients during the last 20 years has been associated with prolonged survival and lower risk of recurrent ischaemic events, although a plateauing is seen since around 2008.

Eligibility for lipid-lowering therapy when applying systemic coronary risk estimation 2 (SCORE2) according to guidelines on apparently healthy middle-aged individuals.

AIMS: To estimate the proportion eligible for lipid-lowering therapy (LLT) when using the systemic coronary risk estimation 2 (SCORE2) on apparently healthy individuals. METHODS: Individuals aged 50-64 years were randomly invited to the Swedish cardiopulmonary bioimage study (SCAPIS, n=30,154). Participants with previous atherosclerotic cardiovascular disease (CVD), diabetes mellitus, or chronic kidney disease were excluded. The 10-year risk of CVD was estimated using the SCORE2 equation and the multicell chart. Eligibility for LLT was estimated according to the 2021 European Society of Cardiology CVD prevention guidelines. Presence of coronary atherosclerosis was determined using coronary computed tomography angiography (CCTA). RESULTS: Among 26,570 apparently healthy individuals, 32% had high, and 4% had very-high 10-year CVD risk, according to the SCORE2 equation. Among high and very-high risk individuals, 99% had LDL-C levels above guideline goals making 35% of the total population eligible for LLT. Of those eligible, undergoing imaging, 38% had no signs of coronary atherosclerosis according to CCTA. Using the SCORE2 chart, 52% of the population were eligible for LLT, of which 44% had no signs of coronary atherosclerosis. In those with high or very-high risk, ongoing LLT was reported in 7% and another 11% received LLT within six months after study participation. CONCLUSIONS: Nearly all apparently healthy individuals with high and very-high CVD risk, or 35% of the total population, were eligible for LLT according to guidelines, and a large proportion had no signs of atherosclerosis. Compared with the SCORE2 equation, the SCORE2 chart resulted in more individuals being eligible for LLT.

KEY QUESTIONS: What proportion of an apparently healthy middle-aged population would be eligible for lipid-lowering therapy (LLT) according to the 2021 ESC guidelines when using SCORE2? What proportion of those eligible for LLT have atherosclerosis according to coronary imaging? KEY FINDING: According to the guidelines, nearly all individuals categorized as high and very-high risk according to the SCORE2 equation, or 35% of the total population, were eligible for LLT, of which 38% had no signs of coronary atherosclerosis. These proportions increased when the SCORE2 multicell chart was used. TAKE-HOME MESSAGE: Implementing SCORE2 and the ESC guidelines would result in more than one in three apparently healthy middle-aged individuals being eligible for LLT. A significant proportion would have no signs of coronary atherosclerosis.

Clinical Outcome of Revascularization Deferral With Instantaneous Wave-Free Ratio and Fractional Flow Reserve: A 5-Year Follow-Up Substudy From the iFR-SWEDEHEART Trial.

Background Although physiology-based assessment of coronary artery stenosis using instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) are established methods of guiding coronary revascularization, its clinical outcome in long-term deferral needs further evaluation, especially with acute coronary syndrome as a clinical presentation. The aim was to evaluate the long-term clinical outcome of deferral of revascularization based on iFR or FFR. Methods and Results This is a substudy of the iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trial, where patients deferred from revascularization from each study arm were selected. Nine hundred eight patients deferred from coronary revascularization with iFR (n=473) and FFR (n=435) were followed for 5 years. The national quality registry, SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies), was used for patient data collection and clinical follow-up. The end point was major adverse cardiac events and their individual components all-cause death, cardiovascular death, noncardiovascular death, nonfatal myocardial infarction, and unplanned revascularization. No significant difference was found in major adverse cardiac events (iFR 18.6% versus FFR 16.8%; adjusted hazard ratio, 1.08 [95% CI, 0.79-1.48]; P=0.63) or their individual components. Conclusions No differences in clinical outcomes after 5-year follow-up were noted when comparing iFR versus FFR as methods for deferral of coronary revascularization in patients presenting with stable angina pectoris and acute coronary syndrome. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02166736.

Association of beta-blockers beyond 1 year after myocardial infarction and cardiovascular outcomes.

OBJECTIVE: Beta-blockers (BB) are an established treatment following myocardial infarction (MI). However, there is uncertainty as to whether BB beyond the first year of MI have a role in patients without heart failure or left ventricular systolic dysfunction (LVSD). METHODS: A nationwide cohort study was conducted including 43 618 patients with MI between 2005 and 2016 in the Swedish register for coronary heart disease. Follow-up started 1 year after hospitalisation (index date). Patients with heart failure or LVSD up until the index date were excluded. Patients were allocated into two groups according to BB treatment. Primary outcome was a composite of all-cause mortality, MI, unscheduled revascularisation and hospitalisation for heart failure. Outcomes were analysed using Cox and Fine-Grey regression models after inverse propensity score weighting. RESULTS: Overall, 34 253 (78.5%) patients received BB and 9365 (21.5%) did not at the index date 1 year following MI. The median age was 64 years and 25.5% were female. In the intention-to-treat analysis, the unadjusted rate of primary outcome was lower among patients who received versus not received BB (3.8 vs 4.9 events/100 person-years) (HR 0.76; 95% CI 0.73 to 1.04). Following inverse propensity score weighting and multivariable adjustment, the risk of the primary outcome was not different according to BB treatment (HR 0.99; 95% CI 0.93 to 1.04). Similar findings were observed when censoring for BB discontinuation or treatment switch during follow-up. CONCLUSION: Evidence from this nationwide cohort study suggests that BB treatment beyond 1 year of MI for patients without heart failure or LVSD was not associated with improved cardiovascular outcomes.

Prevalence of angina pectoris and association with coronary atherosclerosis in a general population.

OBJECTIVE: To assess the contemporary prevalence of, and factors associated with angina pectoris symptoms, and to examine the relationship to coronary atherosclerosis in a middle-aged, general population. METHODS: Data were based on the Swedish CArdioPulmonary bioImage Study (SCAPIS), in which 30 154 individuals were randomly recruited from the general population between 2013 and 2018. Participants that completed the Rose Angina Questionnaire were included and categorised as angina or no angina. Subjects with a valid coronary CT angiography (CCTA) were categorised by degree of coronary atherosclerosis; ≥50% obstruction (obstructive coronary atherosclerosis), <50% obstruction or any atheromatosis (non-obstructive coronary atherosclerosis) or none (no coronary atherosclerosis). RESULTS: The study population consisted of 28 974 questionnaire responders (median age 57.4 years, female 51.6%, hypertension 19.9%, hyperlipidaemia 7.9%, diabetes mellitus 3.7%), of which 1025 (3.5%) fulfilled the criteria of angina. Coronary atherosclerosis was more common in individuals having angina compared with those with no angina (n=24 602, obstructive coronary atherosclerosis 11.8% vs 5.4%, non-obstructive coronary atherosclerosis 38.9% vs 37.0%, no coronary atherosclerosis 49.4% vs 57.7%, all p<0.001). Factors independently associated with angina were birthplace outside of Sweden (OR 2.58 (95% CI 2.10 to 2.92)), low educational level (OR 1.41 (1.10 to 1.79)), unemployment (OR 1.51 (1.27 to 1.81)), poor economic status (OR 1.85 (1.38 to 2.47)), symptoms of depression (OR 1.63 (1.38 to 1.92)) and high degree of stress (OR 2.92 (1.80 to 4.73)). CONCLUSION: Angina pectoris symptoms are common (3.5%) among middle-aged individuals of the general population of Sweden, though with low association to obstructive coronary atherosclerosis. Sociodemographic and psychological factors are highly associated with angina symptoms, irrespective of degree of coronary atherosclerosis.

Association between high-sensitivity C-reactive protein and coronary atherosclerosis in a general middle-aged population.

Despite abundant knowledge about the relationship between inflammation and coronary atherosclerosis, it is still unknown whether systemic inflammation measured as high-sensitivity C-reactive protein (hsCRP) is associated with coronary atherosclerosis in a general population. This study aimed to examine the association between hsCRP and coronary computed tomography angiography (CCTA)-detected coronary atherosclerosis in a population-based cohort. Out of 30,154 randomly invited men and women aged 50 to 64 years in the Swedish Cardiopulmonary Bioimage Study (SCAPIS), 25,408 had a technically acceptable CCTA and analysed hsCRP. Coronary atherosclerosis was defined as presence of plaque of any degree in any of 18 coronary segments. HsCRP values were categorised in four groups. Compared with hsCRP below the detection limit, elevated hsCRP (≥ 2.3 mg/L) was weakly associated with any coronary atherosclerosis (OR 1.15, 95% CI 1.07-1.24), coronary diameter stenosis ≥ 50% (OR 1.27, 95% CI 1.09-1.47), ≥ 4 segments involved (OR 1.13, 95% CI 1.01-1.26 ) and severe atherosclerosis (OR 1.33, 95% CI 1.05-1.69) after adjustment for age, sex and traditional risk factors. The associations were attenuated after further adjustment for body mass index (BMI), although elevated hsCRP still associated with noncalcified plaques (OR 1.16, 95% CI 1.02-1.32), proposed to be more vulnerable. In conclusion, the additional value of hsCRP to traditional risk factors in detection of coronary atherosclerosis is low. The association to high-risk noncalcified plaques, although unlikely through a causal pathway, could explain the relationship between hsCRP and clinical coronary events in numerous studies.

Design and rationale of randomized evaluation of decreased usage of beta-blockers after acute myocardial infarction (REDUCE-AMI).

AIMS: Most trials showing benefit of beta-blocker treatment after myocardial infarction (MI) included patients with large MIs and are from an era before modern biomarker-based MI diagnosis and reperfusion treatment. The aim of the randomized evaluation of decreased usage of beta-blockers after acute myocardial infarction (REDUCE-AMI) trial is to determine whether long-term oral beta-blockade in patients with an acute MI and preserved left ventricular ejection fraction (EF) reduces the composite endpoint of death of any cause or recurrent MI. METHODS AND RESULTS: It is a registry-based, randomized, parallel, open-label, multicentre trial performed at 38 centres in Sweden, 1 centre in Estonia, and 6 centres in New Zealand. About 5000 patients with an acute MI who have undergone coronary angiography and with EF ≥ 50% will be randomized to long-term treatment with beta-blockade or not. The primary endpoint is the composite endpoint of death of any cause or new non-fatal MI. There are several secondary endpoints, including all-cause death, cardiovascular death, new MI, readmission because of heart failure and atrial fibrillation, symptoms, functional status, and health-related quality of life after 6-10 weeks and after 1 year of treatment. Safety endpoints are bradycardia, AV-block II-III, hypotension, syncope or need for pacemaker, asthma or chronic obstructive pulmonary disease, and stroke. CONCLUSION: The results from REDUCE-AMI will add important evidence regarding the effect of beta-blockers in patients with MI and preserved EF and may change guidelines and clinical practice.

Nationwide observational study of incidence, management and outcome of spontaneous coronary artery dissection: a report from the Swedish Coronary Angiography and Angioplasty register.

OBJECTIVES: The aim of this study was to conduct a nationwide all comer description of incidence, contemporary management and outcome in Swedish spontaneous coronary artery dissection (SCAD) patients. The incidence of SCAD as well as the management and outcome of these patients is not well described. DESIGN: A nationwide observational study. PARTICIPANTS AND SETTING: All patients with SCAD registered in the Swedish Coronary Angiography and Angioplasty Register from 2015 to 2017 were included. The index angiographies of patients with registered SCAD were re-evaluated at each centre to confirm the diagnosis. Patients with non-SCAD myocardial infarction (MI) (n=32 601) were used for comparison. OUTCOME MEASURES: Outcomes included all-cause mortality, reinfarction or acute coronary reangiography. RESULTS: This study found 147 SCAD patients, rendering an incidence of 0.74 per 100 000 per year and a prevalence of 0.43% of all MIs. The average age was 52.9 years, 75.5% were women and 47.6% presented with ST-segment elevation MI. Median follow-up time for major adverse cardiac event was 17.3 months. Percutaneous coronary intervention was attempted in 40.1% of SCAD patients and 30.6% received stent. The use of antithrombotic agents was similar between the groups and there was no difference regarding outcomes, 10.9% vs 13.4%, p=0.75. Mortality was lower in SCAD patients, 2.7% vs 8.0%, p=0.03, whereas SCAD patients more often underwent acute reangiography, 9.5% vs 4.6%, p<0.01. CONCLUSION: In this nationwide, all comer Swedish study, the overall incidence of SCAD was low, including 25% men which is more and in contrast to previous studies. Compared with non-SCAD MI, SCAD patients were younger, with lower cardiovascular risk burden, yet suffered substantial mortality and morbidity and more frequently underwent acute coronary reangiography.

Trends in Clinical Practice and Outcomes After Percutaneous Coronary Intervention of Unprotected Left Main Coronary Artery.

Background The use of percutaneous coronary intervention (PCI) to treat unprotected left main coronary artery disease has expanded rapidly in the past decade. We aimed to describe nationwide trends in clinical practice and outcomes after PCI for left main coronary artery disease. Methods and Results Patients (n=4085) enrolled in the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) as undergoing PCI for left main coronary artery disease from 2005 to 2017 were included. A count regression model was used to analyze time-related differences in procedural characteristics. The 3-year major adverse cardiovascular and cerebrovascular event rate defined as death, myocardial infarction, stroke, and repeat revascularization was calculated with the Kaplan-Meier estimator and Cox proportional hazard model. The number of annual PCI procedures grew from 121 in 2005 to 589 in 2017 (389%). The increase was greater for men (479%) and individuals with diabetes (500%). Periprocedural complications occurred in 7.9%, decreasing from 10% to 6% during the study period. A major adverse cardiovascular and cerebrovascular event occurred in 35.7% of patients, falling from 45.6% to 23.9% (hazard ratio, 0.56; 95% CI, 0.41-0.78; P=0.001). Radial artery access rose from 21.5% to 74.2% and intracoronary diagnostic procedures from 14.0% to 53.3%. Use of bare-metal stents and first-generation drug-eluting stents fell from 19.0% and 71.9%, respectively, to 0, with use of new-generation drug-eluting stents increasing to 95.2%. Conclusions Recent changes in clinical practice relating to PCI for left main coronary artery disease are characterized by a 4-fold rise in procedures conducted, increased use of evidence-based adjunctive treatment strategies, intracoronary diagnostics, newer stents, and more favorable outcomes.

Safety of early hospital discharge following admission with ST-elevation myocardial infarction treated with percutaneous coronary intervention: a nationwide cohort study.

BACKGROUND: The Second Primary Angioplasty in Myocardial Infarction (PAMI-II) risk score is recommended by guidelines to identify low-risk patients with ST-elevation myocardial infarction (STEMI) for an early discharge strategy. AIMS: We aimed to assess the safety of early discharge (≤2 days) for low-risk STEMI patients treated with primary percutaneous coronary intervention (PCI). METHODS: Using nationwide data from the SWEDEHEART registry, we identified patients with STEMI treated with primary PCI during the period 2009-2017, of whom 8,092 (26.4%) were identified as low risk with the PAMI-II score. Low-risk patients were stratified according to their length of hospital stay (≤2 days vs >2 days). The primary endpoint was major adverse cardiovascular events (MACE, including death, reinfarction treated with PCI, stroke or heart failure hospitalisation) at one year, assessed using a Cox proportional hazards model with propensity score as well as an inverse probability weighting propensity score of average treatment effect to adjust for confounders. RESULTS: A total of 1,449 (17.9%) patients were discharged ≤2 days from admission. After adjustment, the one-year MACE rate was not higher for patients discharged at >2 days from admission than for patients discharged ≤2 days (4.3% vs 3.2%; adjusted HR 1.31, 95% confidence interval [CI]: 0.92-1.87, p=0.14), and no difference was observed regarding any of the individual components of the main outcome. Results were consistent across all subgroups with no difference in MACE between early and late discharge patients. CONCLUSIONS: Nationwide observational data suggest that early discharge of low-risk patients with STEMI treated with PCI is not associated with an increase in one-year MACE.