FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction.

BACKGROUND: The benefit of fractional flow reserve (FFR)-guided complete revascularization in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease remains unclear. METHODS: In this multinational, registry-based, randomized trial, we assigned patients with STEMI or very-high-risk non-STEMI (NSTEMI) and multivessel disease who were undergoing primary percutaneous coronary intervention (PCI) of the culprit lesion to receive either FFR-guided complete revascularization of nonculprit lesions or no further revascularization. The primary outcome was a composite of death from any cause, myocardial infarction, or unplanned revascularization. The two key secondary outcomes were a composite of death from any cause or myocardial infarction and unplanned revascularization. RESULTS: A total of 1542 patients underwent randomization, with 764 assigned to receive FFR-guided complete revascularization and 778 assigned to receive culprit-lesion-only PCI. At a median follow-up of 4.8 years (interquartile range, 4.3 to 5.2), a primary-outcome event had occurred in 145 patients (19.0%) in the complete-revascularization group and in 159 patients (20.4%) in the culprit-lesion-only group (hazard ratio, 0.93; 95% confidence interval [CI], 0.74 to 1.17; P = 0.53). With respect to the secondary outcomes, no apparent between-group differences were observed in the composite of death from any cause or myocardial infarction (hazard ratio, 1.12; 95% CI, 0.87 to 1.44) or unplanned revascularization (hazard ratio, 0.76; 95% CI, 0.56 to 1.04). There were no apparent between-group differences in safety outcomes. CONCLUSIONS: Among patients with STEMI or very-high-risk NSTEMI and multivessel coronary artery disease, FFR-guided complete revascularization was not shown to result in a lower risk of a composite of death from any cause, myocardial infarction, or unplanned revascularization than culprit-lesion-only PCI at 4.8 years. (Funded by the Swedish Research Council and others; FULL REVASC ClinicalTrials.gov number, NCT02862119.).

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.).

Bivalirudin versus heparin in ST and non-ST-segment elevation myocardial infarction-Outcomes at two years.

BACKGROUND: The registry-based randomized VALIDATE-SWEDEHEART trial (NCT02311231) compared bivalirudin vs. heparin in patients undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI). It showed no difference in the composite primary endpoint of death, MI, or major bleeding at 180 days. Here, we report outcomes at two years. METHODS: Analysis of primary and secondary endpoints at two years of follow-up was prespecified in the study protocol. We report the study results for the extended follow-up time here. RESULTS: In total, 6006 patients were enrolled, 3005 with ST-segment elevation MI (STEMI) and 3001 with Non-STEMI (NSTEMI), representing 70 % of all eligible patients with these diagnoses during the study. The primary endpoint occurred in 14.0 % (421 of 3004) in the bivalirudin group compared with 14.3 % (429 of 3002) in the heparin group (hazard ratio [HR] 0.97; 95 % confidence interval [CI], 0.85-1.11; P = 0.70) at one year and in 16.7 % (503 of 3004) compared with 17.1 % (514 of 3002), (HR 0.97; 95 % CI, 0.96-1.10; P = 0.66) at two years. The results were consistent in patients with STEMI and NSTEMI and across major subgroups. CONCLUSIONS: Until the two-year follow-up, there were no differences in endpoints between patients with MI undergoing PCI and allocated to bivalirudin compared with those allocated to heparin. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02311231.

Prevalence and prognostic impact of left ventricular systolic dysfunction or pulmonary congestion after acute myocardial infarction.

AIMS: The aim was to describe the prevalence, characteristics, and outcome of patients with acute myocardial infarction (MI) developing left ventricular (LV) systolic dysfunction or pulmonary congestion by applying different criteria to define the population. METHODS AND RESULTS: In patients with MI included in the Swedish web-system for enhancement and development of evidence-based care in heart disease (SWEDEHEART) registry, four different sets of criteria were applied, creating four not mutually exclusive subsets of patients: patients with MI and ejection fraction (EF) < 50% and/or pulmonary congestion (subset 1); EF < 40% and/or pulmonary congestion (subset 2); EF < 40% and/or pulmonary congestion and at least one high-risk feature (subset 3, PARADISE-MI like); and EF < 50% and no diabetes mellitus (subset 4, DAPA-MI like). Subsets 1, 2, 3, and 4 constituted 31.6%, 15.0%, 12.8%, and 22.8% of all patients with MI (n = 87 177), respectively. The age and prevalence of different co-morbidities varied between subsets. For median age, 70 to 77, for diabetes mellitus, 22 to 33%; for chronic kidney disease, 22 to 38%, for prior MI, 17 to 21%, for atrial fibrillation, 7 to 14%, and for ST-elevations, 38 to 50%. The cumulative incidence of death or heart failure hospitalization at 3 years was 17.4% (95% CI: 17.1-17.7%) in all MIs; 26.9% (26.3-27.4%) in subset 1; 37.6% (36.7-38.5%) in subset 2; 41.8% (40.7-42.8%) in subset 3; and 22.6% (22.0-23.2%) in subset 4. CONCLUSIONS: Depending on the definition, LV systolic dysfunction or pulmonary congestion is present in 13-32% of all patients with MI and is associated with a two to three times higher risk of subsequent death or HF admission. There is a need to optimize management and improve outcomes for this high-risk population.

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.

Age-Stratified Outcome in Treatment of Left Main Coronary Artery Stenosis: A NOBLE Trial Substudy.

BACKGROUND: In the treatment of left main coronary artery (LMCA) disease, patients' age may affect the clinical outcome after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). This study stratified the clinical outcome according to the age of patients treated for LMCA stenosis with PCI or CABG in the Nordic-Baltic-British Left Main Revascularization (NOBLE) study. METHODS: Patients with LMCA disease were enrolled in 36 centers in northern Europe and randomized 1:1 to treatment by PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST elevation myocardial infarction. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCEs), a composite of all-cause mortality, nonprocedural myocardial infarction, any repeat coronary revascularization, and stroke. Age-stratified analysis was performed for the groups younger and older than 67 years and for patients older than 80 years. RESULTS: For patients ≥67 years, the 5-year MACCEs were 35.7 versus 22.3% (hazard ratio [HR] 1.72 [95% confidence interval [CI] 1.27-2.33], p = 0.0004) for PCI versus CABG. The difference in MACCEs was driven by more myocardial infarctions (10.8 vs. 3.8% HR 3.01 [95% CI 1.52-5.96], p = 0.0009) and more repeat revascularizations (19.5 vs. 10.0% HR 2.01 [95% CI 1.29-3.12], p = 0.002). In patients younger than 67 years, MACCE was 20.5 versus 15.3% (HR 1.38 [95% CI 0.93-2.06], p = 0.11 for PCI versus CABG. All-cause mortality was similar after PCI and CABG in both age-groups. On multivariate analysis, age was a predictor of MACCE, along with PCI, diabetes, and SYNTAX score. CONCLUSIONS: As the overall NOBLE results show revascularization of LMCA disease, age of 67 years or older was associated with lower 5-year MACCE after CABG compared to PCI. Clinical outcomes were not significantly different in the subgroup younger than 67 years, although no significant interaction was present between age and treatment. Mortality was similar for all subgroups (ClinicalTrials.gov identifier: NCT01496651).

Routine Oxygen Therapy Does Not Improve Health-Related Quality of Life in Patients With Acute Myocardial Infarction-Insights From the Randomized DETO2X-AMI Trial.

Background: After decades of ubiquitous oxygen therapy in all patients with acute myocardial infarction (MI), recent guidelines are more restrictive based on lack of efficacy in contemporary trials evaluating hard clinical outcomes in patients without hypoxemia at baseline. However, no evidence regarding treatment effects on health-related quality of life (HRQoL) exists. In this study, we investigated the impact of routine oxygen supplementation on HRQoL 6-8 weeks after hospitalization with acute MI. Secondary objectives included analyses of MI subtypes, further adjustment for infarct size, and oxygen saturation at baseline and 1-year follow-up. Methods: In the DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial, 6,629 normoxemic patients with suspected MI were randomized to oxygen at 6 L/min for 6-12 h or ambient air. In this prespecified analysis, patients younger than 75 years of age with confirmed MI who had available HRQoL data by European Quality of Life Five Dimensions questionnaire (EQ-5D) in the national registry were included. Primary endpoint was the EQ-5D index assessed by multivariate linear regression at 6-10 weeks after MI occurrence. Results: A total of 3,086 patients (median age 64, 22% female) were eligible, 1,518 allocated to oxygen and 1,568 to ambient air. We found no statistically significant effect of oxygen therapy on EQ-5D index (-0.01; 95% CI: -0.03-0.01; p = 0.23) or EQ-VAS score (-0.57; 95% CI: -1.88-0.75; p = 0.40) compared to ambient air after 6-10 weeks. Furthermore, no significant difference was observed between the treatment groups in EQ-5D dimensions. Results remained consistent across MI subtypes and at 1-year follow-up, including further adjustment for infarct size or oxygen saturation at baseline. Conclusions: Routine oxygen therapy provided to normoxemic patients with acute MI did not improve HRQoL up to 1 year after MI occurrence. Clinical Trial Registration: ClinicalTrials.gov number, NCT01787110.

Avoiding Routine Oxygen Therapy in Patients With Myocardial Infarction Saves Significant Expenditure for the Health Care System-Insights From the Randomized DETO2X-AMI Trial.

Background: Myocardial infarction (MI) occurs frequently and requires considerable health care resources. It is important to ensure that the treatments which are provided are both clinically effective and economically justifiable. Based on recent new evidence, routine oxygen therapy is no longer recommended in MI patients without hypoxemia. By using data from a nationwide randomized clinical trial, we estimated oxygen therapy related cost savings in this important clinical setting. Methods: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial randomized 6,629 patients from 35 hospitals across Sweden to oxygen at 6 L/min for 6-12 h or ambient air. Costs for drug and medical supplies, and labor were calculated per patient, for the whole study population, and for the total annual care episodes for MI in Sweden (N = 16,100) with 10 million inhabitants. Results: Per patient, costs were estimated to 36 USD, summing up to a total cost of 119,832 USD for the whole study population allocated to oxygen treatment. Applied to the annual care episodes for MI in Sweden, costs sum up to between 514,060 and 604,777 USD. In the trial, 62 (2%) patients assigned to oxygen and 254 (8%) patients assigned to ambient air developed hypoxemia. A threshold analysis suggested that up to a cut-off of 624 USD spent for hypoxemia treatment related costs per patient, avoiding routine oxygen therapy remains cost saving. Conclusions: Avoiding routine oxygen therapy in patients with suspected or confirmed MI without hypoxemia at baseline saves significant expenditure for the health care system both with regards to medical and human resources. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT01787110.

Agreement between nonculprit stenosis follow-up iFR and FFR after STEMI (iSTEMI substudy).

OBJECTIVE: To evaluate agreement between instantaneous wave free ratio (iFR) and fractional flow reserve (FFR) for the functional assessment of nonculprit coronary stenoses at staged follow-up after ST-segment elevation myocardial infarction (STEMI). RESULTS: We measured iFR and FFR at staged follow-up in 112 STEMI patients with 146 nonculprit stenoses. Median interval between STEMI and follow-up was 16 (interquartile range 5-32) days. Agreement between iFR and FFR was 77% < 5 days after STEMI and 86% after ≥ 5 days (p = 0.19). Among cases with disagreement, the proportion of cases with hemodynamically significant iFR and non-significant FFR were different when assessed < 5 days (5 in 8, 63%) versus ≥ 5 days (3 in 15, 20%) after STEMI (p = 0.04). Overall classification agreement between iFR and FFR was comparable to that observed in stable patients. Time interval between STEMI and follow-up evaluation may impact agreement between iFR and FFR.

[Platypnea-orthodeoxia syndrome: a neglected cause of dyspnea?] / Platypné­ortodeoxisyndrom ­ förbisedd orsak till dyspné.

A 68-year-old woman presented with progressive and severe effort-related dyspnea. Her history included an ischemic stroke at age 43. Routine exams were normal. Cardiopulmonary exercise testing (CPET) showed a reduction in PaO2 from 11.8 kPa to 4.8 kPa. Repeated CPET with 100 % inhaled O2 improved the drop in PaO2 marginally. Transesophageal echocardiography revealed a shunt from right to left through a patent foramen ovale (PFO). A right heart catheterization showed normal pressures and no signs of intrapulmonary shunting. The PFO was closed percutaneously and the patient's symptoms resolved almost completely. Platypnea-orthodeoxia syndrome is an uncommon disorder where the pathophysiological mechanisms include a right-to-left shunt, either intracardiac or pulmonary. The most common intracardiac shunt related to the syndrome is a PFO. Platypnea-orthodeoxia syndrome, although rare, merits our attention, since it is often easily treatable. The key finding is desaturation on standing up.

Instantaneous wave-free ratio cutoff values for nonculprit stenosis classification in patients with ST-segment elevation myocardial infarction (an iSTEMI substudy).

OBJECTIVES: The instantaneous wave-free ratio cutoff value of <0.90 for hemodynamic significance of coronary stenoses has been validated in stable patients. We examined different cutoff values in the evaluation of nonculprit stenoses in patients with ST-segment elevation myocardial infarction. METHODS: We measured instantaneous wave-free ratio across nonculprit stenoses in the acute setting and at follow-up in 120 patients with ST-segment elevation myocardial infarction and 157 nonculprit stenoses, of which, 113 patients with 147 nonculprit stenoses completed follow-up. METHODS: The prevalence of nonculprit stenosis hemodynamic significance was 52% in the acute setting and 41% at follow-up. With follow-up, instantaneous wave-free ratio as reference, acute instantaneous wave-free ratio >0.90 had a negative predictive value of 89%. Acute instantaneous wave-free ratio <0.90 had a positive predictive value of 68%. Acute instantaneous wave-free ratio >0.93 had a negative predictive value of 100%. Acute instantaneous wave-free ratio <0.86 and <0.83 had positive predictive values of 71 and 77%. Using acute instantaneous wave-free ratio <0.90 as cutoff for hemodynamic significance yielded the highest degree of classification agreement between acute and follow-up instantaneous wave-free ratio. CONCLUSIONS: In patients with ST-segment elevation myocardial infarction, acute instantaneous wave-free ratio with the cutoff values <0.90 for hemodynamic significance appears optimal in the evaluation of nonculprit stenoses and has a high negative predictive value and a moderate positive predictive value.

Intravascular ultrasound to guide left main stem intervention: a NOBLE trial substudy.

AIMS: We aimed to investigate the association between the use and findings of IVUS with clinical outcomes in the PCI arm of a randomised trial of LMS PCI. METHODS AND RESULTS: The NOBLE trial randomised patients with LMS disease to treatment by PCI or CABG. Of 603 patients treated by PCI, 435 (72%) underwent post-PCI IVUS assessment, 224 of which were analysed in a core laboratory. At five years, the composite of MACCE was 18.9% if post-PCI IVUS was performed versus 25.0% if it was not performed (p=0.45, after adjustment). Overall repeat revascularisation was not reduced (10.6% vs 16.5%, p=0.11); however, LMS TLR was (5.1% vs 11.6%, p=0.01) if IVUS was used. For comparison of stent expansion, LMS MSA was split into tertiles. We found no significant difference in MACCE, death, myocardial infarction or stent thrombosis between tertiles. There was a significant difference between the lower and upper tertiles for repeat revascularisation (17.6% vs 5.2%, p=0.02) and LMS TLR (12.2% vs 0%, p=0.002). CONCLUSIONS: Post-PCI IVUS assessment and adequate stent expansion are not associated with reduced MACCE; however, there is an association with reduced LMS TLR. The use of intracoronary imaging to prevent stent underexpansion in LMS PCI is likely to improve outcomes.

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.

Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non-inferiority NOBLE trial.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used in revascularisation of patients with left main coronary artery disease in place of the standard treatment, coronary artery bypass grafting (CABG). The NOBLE trial aimed to evaluate whether PCI was non-inferior to CABG in the treatment of left main coronary artery disease and reported outcomes after a median follow-up of 3·1 years. We now report updated 5-year outcomes of the trial. METHODS: The prospective, randomised, open-label, non-inferiority NOBLE trial was done at 36 hospitals in nine northern European countries. Patients with left main coronary artery disease requiring revascularisation were enrolled and randomly assigned (1:1) to receive PCI or CABG. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, repeat revascularisation, and stroke. Non-inferiority of PCI to CABG was defined as the upper limit of the 95% CI of the hazard ratio (HR) not exceeding 1·35 after 275 MACCE had occurred. Secondary endpoints included all-cause mortality, non-procedural myocardial infarction, and repeat revascularisation. Outcomes were analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01496651. FINDINGS: Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were enrolled and allocated to PCI (n=598) or CABG (n=603), with 17 subsequently lost to early follow-up. 592 patients in each group were included in this analysis. At a median of 4·9 years of follow-up, the predefined number of events was reached for adequate power to assess the primary endpoint. Kaplan-Meier 5-year estimates of MACCE were 28% (165 events) for PCI and 19% (110 events) for CABG (HR 1·58 [95% CI 1·24-2·01]); the HR exceeded the limit for non-inferiority of PCI compared to CABG. CABG was found to be superior to PCI for the primary composite endpoint (p=0·0002). All-cause mortality was estimated in 9% after PCI versus 9% after CABG (HR 1·08 [95% CI 0·74-1·59]; p=0·68); non-procedural myocardial infarction was estimated in 8% after PCI versus 3% after CABG (HR 2·99 [95% CI 1·66-5·39]; p=0·0002); and repeat revascularisation was estimated in 17% after PCI versus 10% after CABG (HR 1·73 [95% CI 1·25-2·40]; p=0·0009). INTERPRETATION: In revascularisation of left main coronary artery disease, PCI was associated with an inferior clinical outcome at 5 years compared with CABG. Mortality was similar after the two procedures but patients treated with PCI had higher rates of non-procedural myocardial infarction and repeat revascularisation. FUNDING: Biosensors.

Effect of Oxygen Therapy on Cardiovascular Outcomes in Relation to Baseline Oxygen Saturation.

OBJECTIVES: The aim of this study was to determine the effect of supplemental oxygen in patients with myocardial infarction (MI) on the composite of all-cause death, rehospitalization with MI, or heart failure related to baseline oxygen saturation. A secondary objective was to investigate outcomes in patients developing hypoxemia. BACKGROUND: In the DETO2X-AMI (Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction) trial, 6,629 normoxemic patients with suspected MI were randomized to oxygen at 6 l/min for 6 to 12 h or ambient air. METHODS: The study population of 5,010 patients with confirmed MI was divided by baseline oxygen saturation into a low-normal (90% to 94%) and a high-normal (95% to 100%) cohort. Outcomes are reported within 1 year. To increase power, all follow-up time (between 1 and 4 years) was included post hoc, and interaction analyses were performed with oxygen saturation as a continuous covariate. RESULTS: The composite endpoint of all-cause death, rehospitalization with MI, or heart failure occurred significantly more often in patients in the low-normal cohort (17.3%) compared with those in the high-normal cohort (9.5%) (p < 0.001), and most often in patients developing hypoxemia (23.6%). Oxygen therapy compared with ambient air was not associated with improved outcomes regardless of baseline oxygen saturation (interaction p values: composite endpoint, p = 0.79; all-cause death, p = 0.33; rehospitalization with MI, p = 0.86; hospitalization for heart failure, p = 0.35). CONCLUSIONS: Irrespective of oxygen saturation at baseline, we found no clinically relevant beneficial effect of routine oxygen therapy in normoxemic patients with MI regarding cardiovascular outcomes. Low-normal baseline oxygen saturation or development of hypoxemia was identified as an independent marker of poor prognosis. (An Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction; NCT01787110).

Change in mitral regurgitation severity impacts survival after transcatheter aortic valve replacement.

BACKGROUND: The impact of a change in mitral regurgitation (MR) following TAVR is unknown. We studied the impact of baseline MR and early post-procedural change in MR on survival following TAVR. METHODS: The SWEDEHEART registry included all TAVRs performed in Sweden. Patients were dichotomized into no/mild and moderate/severe MR groups. Vital status, echocardiographic data at baseline and within 7 days after TAVR were analyzed. RESULTS: 1712 patients were included. 1404 (82%) had no/mild MR and 308 (18%) had moderate/severe MR. Baseline moderate/severe MR conferred a higher mortality rate at 5-year follow-up (adjusted HR 1.29, CI 1.01-1.65, p = 0.04). Using persistent ≤mild MR as the reference, when moderate/severe MR persisted or if MR worsened from ≤mild at baseline to moderate/severe after TAVR, higher 5-year mortality rates were seen (adjusted HR 1.66, CI 1.17-2.34, p = 0.04; adjusted HR 1.97, CI 1.29-3.00, p = 0.002, respectively). If baseline moderate/severe MR improved to ≤mild after TAVR no excess mortality was seen (HR 1.09, CI 0.75-1.58, p = 0.67). Paravalvular aortic regurgitation (PVL) was inversely associated with MR improvement after TAVR (OR 0.4, 95%: CI 0.17-0.94; p = 0.034). Atrial fibrillation (OR 2.1, 95% CI: 1.27-3.39, p = 0.004), self-expanding valve (OR 3.8, 95% CI: 2.08-7.14, p < 0.0001), and PVL (4.3, 95% CI 2.32-7.78. p < 0.0001) were associated with MR worsening. CONCLUSIONS: Moderate/severe baseline MR in patients undergoing TAVR is associated with a mortality increase during 5 years of follow-up. This risk is offset if MR improves to ≤mild, whereas worsening of MR after TAVR is associated with a 2-fold mortality increase.

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.

Oxygen therapy in ST-elevation myocardial infarction.

Aims: To determine whether supplemental oxygen in patients with ST-elevation myocardial infarction (STEMI) impacts on procedure-related and clinical outcomes. Methods and results: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial randomized patients with suspected myocardial infarction (MI) to receive oxygen at 6 L/min for 6-12 h or ambient air. In this pre-specified analysis, we included only STEMI patients who underwent percutaneous coronary intervention (PCI). In total, 2807 patients were included, 1361 assigned to receive oxygen, and 1446 assigned to ambient air. The pre-specified primary composite endpoint of all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis at 1 year occurred in 6.3% (86 of 1361) of patients allocated to oxygen compared to 7.5% (108 of 1446) allocated to ambient air [hazard ratio (HR) 0.85, 95% confidence interval (95% CI) 0.64-1.13; P = 0.27]. There was no difference in the rate of death from any cause (HR 0.86, 95% CI 0.61-1.22; P = 0.41), rate of rehospitalization for MI (HR 0.92, 95% CI 0.57-1.48; P = 0.73), rehospitalization for cardiogenic shock (HR 1.05, 95% CI 0.21-5.22; P = 0.95), or stent thrombosis (HR 1.27, 95% CI 0.46-3.51; P = 0.64). The primary composite endpoint was consistent across all subgroups, as well as at different time points, such as during hospital stay, at 30 days and the total duration of follow-up up to 1356 days. Conclusions: Routine use of supplemental oxygen in normoxemic patients with STEMI undergoing primary PCI did not significantly affect 1-year all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis.

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.