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BACKGROUND: In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure), dapagliflozin, added to guideline-recommended therapies, reduced the risk of mortality and heart failure (HF) hospitalization. We examined the frequency and significance of episodes of outpatient HF worsening, requiring the augmentation of oral therapy, and the effects of dapagliflozin on these additional events.METHODS: Patients in New York Heart Association functional class II to IV, with a left ventricular ejection fraction ≤40% and elevation of NT-proBNP (N-terminal pro-B-type natriuretic peptide), were eligible. The primary outcome was the composite of an episode of worsening HF (HF hospitalization or an urgent HF visit requiring intravenous therapy) or cardiovascular death, whichever occurred first. An additional prespecified exploratory outcome was the primary outcome plus worsening HF symptoms/signs leading to the initiation of new, or the augmentation of existing, oral treatment.RESULTS: Overall, 36% more patients experienced the expanded, in comparison with the primary, composite outcome. In the placebo group, 684 of 2371 (28.8%) patients and, in the dapagliflozin group, 527 of 2373 (22.2%) participants experienced the expanded outcome (hazard ratio, 0.73 [95% CI, 0.65-0.82]; P<0.0001). Each component of the composite was reduced significantly by dapagliflozin. Over the median follow-up of 18.2 months, the number of patients needed to treat with dapagliflozin to prevent 1 experiencing an episode of fatal or nonfatal worsening was 16. Among the 4744 randomly assigned patients, the first episode of worsening was outpatient augmentation of treatment in 407 participants (8.6%), an urgent HF visit with intravenous therapy in 20 (0.4%), HF hospitalization in 489 (10.3%), and cardiovascular death in 295 (6.2%). The adjusted risk of death from any cause (in comparison with no event) after an outpatient worsening was hazard ratio, 2.67 (95% CI

Importance: Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients with HFrEF, even those without diabetes. Objective: To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes. Design, Setting, and Participants: Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. Interventions: Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy. Main Outcomes and Measures: The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%. Results: Among 4744 patients randomized (mean age, 66 years; 1109 [23%] women; 2605 [55%] without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 [95% CI, 0.60-0.88]). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 [95% CI, 0.63-0.90]) (P value for interaction =.80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 [95% CI, 0.47-0.96]). In patients with a glycated hemoglobin of at

Background: The implementation of high-sensitivity cardiac troponin T (hs-cTnT) assays and a cutoff based on the 99th cTnT percentile in the evaluation of patients with suspected acute coronary syndrome has not been uniform due to uncertain effects on health benefits and utilization of limited resources. Methods: Clinical and laboratory data from patients with chest pain or dyspnea at the emergency department (ED) were evaluated before (n = 20516) and after (n = 18485) the lowering of the hs-cTnT cutoff point from 40 ng/L to the 99th hs-cTnT percentile of 14 ng/L in February 2012. Myocardial infarction (MI) was diagnosed at the discretion of the attending clinicians responsible for the patient. Results: Following lowering of the hs-cTnT cutoff point fewer ED patients with chest pain or dyspnea as the principal complaint were analyzed with an hs-cTnT sample (81% vs. 72%, p < 0.001). Overall 30-day mortality was unaffected but increased among patients not analyzed with an hs-cTnT sample (5.3% vs. 7.6%, p < 0.001). The MI frequency was unchanged (4.0% vs. 3.9%, p = 0.72) whereas admission rates decreased (51% vs. 45%, p < 0.001) as well as hospital costs. Coronary angiographies were used more frequently (2.8% vs. 3.3%, p = 0.004) but with no corresponding change in coronary interventions. Conclusions: At the participating hospital, lowering of the hs-cTnT cutoff point to the 99th percentile decreased admissions and hospital costs but did not result in any apparent prognostic or treatment benefits for the patients.

Objectives To evaluate 90-day cardiovascular outcome in patients after myocardial infarction (MI) in relation to different subtypes of atrial fibrillation (AF) and MI. Methods We studied 155 071 hospital survivors of MI between 2000 and 2009 in Swedish registries. AF subtypes were defined according to history of AF and in-hospital ECG recordings. Clinical outcomes were evaluated with multivariable Cox models. Results AF was documented in 24 023 (15.5%) cases. The AF subtypes were new-onset AF with sinus rhythm at discharge (3.7%), new-onset AF with AF at discharge (3.9%), paroxysmal AF (4.9%) and chronic AF (3.0%). The event rate per 100 person-years for the composite cardiovascular outcome (all-cause mortality, MI or ischaemic stroke) was 90.9 in patients with any type of AF versus 45.2 in patients with sinus rhythm, adjusted hazard ratio with 95% CI (HR) 1.28 (1.19 to 1.37). There were no significant differences in the composite cardiovascular outcome between AF subtypes. AF was associated with higher risk of mortality, HR 1.59 (1.41 to 1.80), reinfarction, HR 1.14 (1.05 to 1.24), and ischaemic stroke, HR 2.29 (1.92 to 2.74), respectively. In subgroup analysis, AF was associated with a higher risk of composite cardiovascular outcome in the non-ST-elevation myocardial infarction (NSTEMI) and STelevation myocardial infarction (STEMI) cohort, HR 1.24 (1.13 to 1.36) and HR 1.34 (1.21 to 1.48), respectively, with p value for interaction= 0.23. Conclusions AF is common in the setting of MI and is associated with a higher risk of composite cardiovascular outcome and the individual components; mortality, reinfarction and ischaemic stroke, respectively. No major difference in outcome was observed between AF subtypes. No difference in outcome for AF was observed between the NSTEMI and STEMI cohort.

AIMS: Despite recommendations in recent guidelines for a routine invasive strategy for non-ST-segment elevation acute coronary syndrome (NSTE-ACS), long-term data on the implementation of treatment strategies in clinical practice are not available. Our aim was to provide long-term data on the implementation of a routine invasive strategy in NSTE-ACS in clinical practice. METHODS AND RESULTS: In the SWEDEHEART registry, data from 204,092 consecutive NSTE-ACS patients admitted between 1996 and 2007 were recorded. The use of the routine invasive strategy, retrospectively defined as coronary angiography (and subsequent revascularisation) within three days after admission, increased from 3.8% in the period 1996-1998 to 37.4% in the period 2005-2007. The largest absolute increase in the use of this strategy was observed in low-risk patients, while a similar relative increase was observed in all risk categories. The use of the selective invasive strategy, defined as coronary angiography later than three days after admission or none at all, decreased from 96.2% in the period 1996-1998 to 62.5% in the period 2005-2007. In the total population, there was a gradual decrease in three-year all-cause mortality, from 29.1% in the period 1996-1998 to 23.9% in the period 2005-2007. CONCLUSIONS: There has been an increase in the use of a routine invasive strategy in NSTE-ACS patients over the course of 12 years in Sweden. There was a decrease in three-year mortality over the same time course.

OBJECTIVE: To examine the extent of change in Troponin T levels in patients with non-ST-elevation myocardial infarction (NSTEMI). BACKGROUND: Changes in cardiac troponin levels are required for the diagnosis of NSTEMI, according to the new universal definition of acute myocardial infarction. A relative change of 20-230 % and an absolute change of 7- 9 ng/L have been suggested as cut-off points. METHOD: In a clinical setting, where a change in cTnT was not mandatory for the diagnosis of NSTEMI, serial samples of cTnT were measured with a high-sensitive cTnT (hs-cTnT) assay, and 37 clinical parameters were evaluated in 1178 patients with a final diagnosis of NSTEMI presenting <24h after symptom onset. RESULTS: After six hours of observation, the relative change in the hs-cTnT level remained <20 % in 26 % and the absolute change <9 ng/L in 12 % of the NSTEMI patients. A relative hs-cTnT change <20% was linked to higher long-term mortality across quartiles (p=0.002) and in multivariate analyses (HR 1.61 (1.17-2.21) p=0.004), whereas 30-day mortality was similar across quartiles of relative hs-cTnT change CONCLUSION: Because stable hs-TnT levels are common in patients with a clinical diagnosis of NSTEMI in our hospital, a small hs-cTnT change may not be useful to exclude NSTEMI, particularly as these patients show both short-term and long-term mortality at least as high as patients with large changes in hs-cTnT.

[Riks-HIA will develop a new index for areas with room for improvement]

Context Only limited information is available on the speed of implementation of new evidence-based and guideline-recommended treatments and its association with survival in real life health care of patients with ST-elevation myocardial infarction (STEMI). Objective To describe the adoption of new treatments and the related chances of short-and long-term survival in consecutive patients with STEMI in a single country over a 12-year period. Design, Setting, and Participants The Register of Information and Knowledge about Swedish Heart Intensive Care Admission (RIKS-HIA) records baseline characteristics, treatments, and outcome of consecutive patients with acute coronary syndrome admitted to almost all hospitals in Sweden. This study includes 61 238 patients with a first-time diagnosis of STEMI between 1996 and 2007. Main Outcome Measures Estimated and crude proportions of patients treated with different medications and invasive procedures and mortality over time. Results Of evidence based-treatments, reperfusion increased from 66% (95%, confidence interval [CI], 52%-79%) to 79% (95% CI, 69%-89%; P<.001), primary percutaneous coronary intervention from 12% (95% CI, 11%-14%) to 61% (95% CI, 45%-77%; P<.001), and revascularization from 10% (96% CI, 6%-14%) to 84% (95% CI, 73%-95%; P<.001). The use of aspirin, clopidogrel, beta-blockers, statins, and angiotensin-converting enzyme (ACE) inhibitors all increased: clopidogrel from 0% to 82% (95% CI, 69%-95%; P<.001), statins from 23% (95% CI, 12%-33%) to 83% (95% CI, 75%-91%; P<.001), and ACE inhibitor or angiotensin II receptor blockers from 39% (95% CI, 26%-52%) to 69% (95% CI, 58%-70%; P<.001). The estimated in-hospital, 30-day and 1-year mortality decreased from 12.5% (95% CI, 4.3%-20.6%) to 7.2% (95% CI, 1.7%-12.6%; P<.001); from 15.0% (95% CI, 6.2%-23.7%) to 8.6% (95% CI, 2.7%-14.5%; P<.001); and from 21.0% (95% CI, 11.0%-30.9%) to 13.3% (95% CI, 6.0%-20.4%; P<.001), respectively. After adjus

In patients with ST-segment elevation myocardial infarction treated with fibrinolytics, electrocardiogram-derived measures of ST-segment recovery guide therapy decisions and predict infarct size. The comprehension of these relationships in patients undergoing mechanical reperfusion is limited. We studied 144 patients treated with primary percutaneous coronary intervention. We aimed to define the association between infarct size as determined by cardiac magnetic resonance imaging and different metrics of ST-segment recovery. Electrocardiograms were assessed at baseline and 90 minutes after primary percutaneous coronary intervention. Three methods for calculating and categorizing ST-segment recovery were used: (1) summed ST-segment deviation (STD) resolution analyzed in 3 categories (> or = 70%, > or = 30% to or = 2 mm). Infarct size and ejection fraction were assessed at 4 months by cardiac magnetic resonance imaging. All 3 ST-segment recovery algorithms predicted the final infarct size and cardiac function. Worst-lead residual STD performed the same as, or better than, the more complex methods and identified large subgroups at either end of the risk spectrum (median infarct size from the lowest to highest risk category (percentage of left ventricle: 7.7% [interquartile range 10.8], 13.1% [interquartile range 13.6]; 24.6% [interquartile range 21.1]); with adjusted odds ratios for infarct size greater than the median (reference or = 2 mm, odds ratio 6.3 (95% confidence interval 1.7 to 23.7; c-index 0.781). In conclusion, an electrocardiogram obtained early after primary percutaneous coronary intervention analyzed by a simple algorithm provided prognostic information on the final infarct size and cardiac function.

Acute ST-segment elevation myocardial infarction requires prompt restoration of myocardial perfusion to salvage myocardium at risk of ischemic necrosis and improve clinical outcome. Early resolution of ST-segment elevation during the time after reperfusion has been associated with both these end points. From the ASsessment of the Safety and Efficacy of a New Thrombolytic regimen (ASSENT) 3 trial, 3,425 patients were analyzed to investigate whether the amount of ST-segment resolution, divided into 3 groups (complete, >70%; partial, 30% to 70%; and no resolution, <30%), in the first hour after initiation of therapy was a predictor of final infarct size, estimated by peak creatine kinase and Selvester QRS score on the discharge electrocardiogram. Complete compared with partial and no ST resolution resulted in significantly (p<0.001) smaller infarct sizes of 10.5%, 13.2%, and 15.0% of the left ventricle and significantly (p=0.001) fewer patients with peak creatine >5 times the upper reference level at 50.3%, 71.8%, and 76.3%, respectively. In conclusion, our findings supported previous smaller studies suggesting that early resolution of ST elevation, as a sign of early myocardial reperfusion, resulted in less myocardial damage and preservation of left ventricular function.