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.

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.

Effects of pharmacological interventions on mortality in patients with Takotsubo syndrome: a report from the SWEDEHEART registry.

AIMS: Takotsubo syndrome (TS) is a heart condition mimicking acute myocardial infarction. TS is characterized by a sudden weakening of the heart muscle, usually triggered by physical or emotional stress. In this study, we aimed to investigate the effect of pharmacological interventions on short- and long-term mortality in patients with TS. METHODS AND RESULTS: We analysed data from the SWEDEHEART (the Swedish Web System for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry, which included patients who underwent coronary angiography between 2009 and 2016. In total, we identified 1724 patients with TS among 228 263 individuals in the registry. The average age was 66 ± 14 years, and 77% were female. Nearly half of the TS patients (49.4%) presented with non-ST-elevation acute coronary syndrome, and a quarter (25.9%) presented with ST-elevation myocardial infarction. Most patients (79.1%) had non-obstructive coronary artery disease on angiography, while 11.7% had a single-vessel disease and 9.2% had a multivessel disease. All patients received at least one pharmacological intervention; most of them used beta-blockers (77.8% orally and 8.3% intravenously) or antiplatelet agents [aspirin (66.7%) and P2Y12 inhibitors (43.6%)]. According to the Kaplan-Meier estimator, the probability of all-cause mortality was 2.5% after 30 days and 16.6% after 6 years. The median follow-up time was 877 days. Intravenous use of inotropes and diuretics was associated with increased 30 day mortality in TS [hazard ratio (HR) = 9.92 (P < 0.001) and HR = 3.22 (P = 0.001), respectively], while angiotensin-converting enzyme inhibitors and statins were associated with decreased long-term mortality [HR = 0.60 (P = 0.025) and HR = 0.62 (P = 0.040), respectively]. Unfractionated and low-molecular-weight heparins were associated with reduced 30 day mortality [HR = 0.63 (P = 0.01)]. Angiotensin receptor blockers, oral anticoagulants, P2Y12 antagonists, aspirin, and beta-blockers did not statistically correlate with mortality. CONCLUSIONS: Our findings suggest that some medications commonly used to treat TS are associated with higher mortality, while others have lower mortality. These results could inform clinical decision-making and improve patient outcomes in TS. Further research is warranted to validate these findings and to identify optimal pharmacological interventions for patients with TS.

Characteristics and Outcomes of Patients Receiving a Second Rescue Valve During Transcatheter Aortic Valve Implantation.

Background: Transcatheter aortic valve implantation (TAVI) has become a safe procedure. However, complications occur, including uncommon complications such as valve malposition, which requires the implantation of an additional rescue valve (rescue-AV). The aim was to study the occurrence and outcomes of rescue-AV in a nationwide registry. Methods: The Swedish national TAVI registry was used as the primary data source, where all 6706 TAVI procedures from 2016 to 2021 were retrieved. Nontransfemoral access and planned valve-in-valve were excluded. In total, 79 patients were identified as having had a rescue-AV, and additional detailed data were collected for these patients. This dataset was analyzed for any characteristics that could predispose patients to a rescue-AV. The outcome of patients receiving rescue-AV also was studied. Results: Of the 5948 patients in the study, 1.3% had a rescue-AV. There were few differences between patients receiving 1 valve and rescue-AV patients. For patients receiving a rescue-AV, the 30-day mortality was 15.2% compared to 1.6% in the control group. A poor outcome after rescue-AV was often associated with a second complication; for example, stroke, need for emergency surgery, or heart failure. Among the patients with rescue-AV who survived at least 30 days, landmark analyses showed similar survival rates compared to the control group. Conclusions: Among TAVI patients in a nationwide register, rescue-AV occurred in 1.3% of patients. The 30-day mortality in patients receiving rescue-AV was high, but long-term outcome among 30-day survivors was similar to the control group.

Comparison of diagnostic accuracy of current left bundle branch block and ventricular pacing ECG criteria for detection of occlusion myocardial infarction.

BACKGROUND: Electrocardiographic detection of patients with occlusion myocardial infarction (OMI) can be difficult in patients with left bundle branch block (LBBB) or ventricular paced rhythm (VPR) and several ECG criteria for the detection of OMI in LBBB/VPR exist. Most recently, the Barcelona criteria, which includes concordant ST deviation and discordant ST deviation in leads with low R/S amplitudes, showed superior diagnostic accuracy but has not been validated externally. We aimed to describe the diagnostic accuracy of four available ECG criteria for OMI detection in patients with LBBB/VPR at the emergency department. METHODS: The unweighted Sgarbossa criteria, the modified Sgarbossa criteria (MSC), the Barcelona criteria and the Selvester criteria were applied to chest pain patients with LBBB or VPR in a prospectively acquired database from five emergency departments. RESULTS: In total, 623 patients were included, among which 441 (71%) had LBBB and 182 (29%) had VPR. Among these, 82 (13%) patients were diagnosed with AMI, and an OMI was identified in 15 (2.4%) cases. Sensitivity/specificity of the original unweighted Sgarbossa criteria were 26.7/86.2%, for MSC 60.0/86.0%, for Barcelona criteria 53.3/82.2%, and for Selvester criteria 46.7/88.3%. In this setting with low prevalence of OMI, positive predictive values were low (Sgarbossa: 4.6%; MSC: 9.4%; Barcelona criteria: 6.9%; Selvester criteria: 9.0%) and negative predictive values were high (all >98.0%). CONCLUSIONS: Our results suggests that ECG criteria alone are insufficient in predicting presence of OMI in an ED setting with low prevalence of OMI, and the search for better rapid diagnostic instruments in this setting should continue.

Prognostic value of early sustained ventricular arrhythmias in ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention: A substudy of VALIDATE-SWEDEHEART trial.

Background: Prognostic assessment of ventricular tachycardia (VT) or ventricular fibrillation (VF) in ST-segment elevation myocardial infarction (STEMI) is based mainly on distinguishing between early (<48 hours) and late arrhythmias, and does not take into account its time distribution with regard to reperfusion, or type of arrhythmia. Objective: We analyzed the prognostic value of early ventricular arrhythmias (VAs) in STEMI with regard to their type and timing. Methods: The prespecified analysis of the multicenter prospective Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarctionin Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease evaluated according to Recommended Therapies Registry Trial included 2886 STEMI patients undergoing primary percutaneous coronary intervention (PCI). VA episodes were characterized regarding their type and timing. Survival status at 180 days was assessed through the population registry. Results: Nonmonomorphic VT or VF was observed in 97 (3.4%) and monomorphic VT in 16 (0.5%) patients. Only 3 (2.7%) early VA episodes occurred after 24 hours from symptom onset. VA was associated with higher risk of death (hazard ratio 3.59; 95% confidence interval [CI] 2.01-6.42) after adjustment for age, sex, and STEMI localization. VA after PCI was associated with an increased mortality compared with VA before PCI (hazard ratio 6.68; 95% CI 2.90-15.41). Early VA was associated with in-hospital mortality (odds ratio 7.39; 95% CI 3.68-14.83) but not with long-term prognosis in patients discharged alive. The type of VA was not associated with mortality. Conclusion: VA after PCI was associated with an increased mortality compared with VA before PCI. Long-term prognosis did not differ between patients with monomorphic VT and nonmonomorphic VT or VF, but events were few. VA incidence during 24 to 48 hours of STEMI is negligibly low, thus precluding assessment of its prognostic importance.

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.

Routine revascularization with percutaneous coronary intervention in patients with coronary artery disease undergoing transcatheter aortic valve implantation - the third nordic aortic valve intervention trial - NOTION-3.

BACKGROUND: Coronary artery disease (CAD) frequently coexists with severe aortic valve stenosis (AS) in patients planned for transcatheter aortic valve implantation (TAVI). How to manage CAD in this patient population is still an unresolved question. In particular, it is still not known whether fractional flow reserve (FFR) guided revascularization with percutaneous coronary intervention (PCI) is superior to medical treatment for CAD in terms of clinical outcomes. STUDY DESIGN: The third Nordic Aortic Valve Intervention (NOTION-3) Trial is an open-label investigator-initiated, multicenter multinational trial planned to randomize 452 patients with severe AS and significant CAD to either FFR-guided PCI or medical treatment, in addition to TAVI. Patients are eligible for the study in the presence of at least 1 significant PCI-eligible coronary stenosis. A significant stenosis is defined as either FFR ≤0.80 and/or diameter stenosis >90%. The primary end point is a composite of first occurring all-cause mortality, myocardial infarction, or urgent revascularization (PCI or coronary artery bypass graft performed during unplanned hospital admission) until the last included patient have been followed for 1 year after the TAVI. SUMMARY: NOTION-3 is a multicenter, multinational randomized trial aiming at comparing FFR-guided revascularization vs medical treatment of CAD in patients with severe AS planned for TAVI.

On the Natural History of Coronary Artery Disease: A Longitudinal Nationwide Serial Angiography Study.

Background The long-term course of coronary atherosclerosis has not been studied in large nationwide cohorts. Understanding the natural history of coronary atherosclerosis could help identify patients at risk for future coronary events. Methods and Results All coronary artery segments with <50% luminal stenosis in patients with a first-time coronary angiogram between 1989 and 2017 were identified (n=2 661 245 coronary artery segments in 248 736 patients) and followed until a clinically indicated angiography within 15 years was performed or until death or end of follow-up (April 2018) using SCAAR (Swedish Coronary Angiography and Angioplasty Registry). The stenosis progression and incidence rates were 2.6% and 1.45 (95% CI, 1.43-1.46) per 1000 segment-years, respectively. The greatest progression rate occurred in the proximal and middle segments of the left anterior descending artery. Male sex and diabetes were associated with a 2-fold increase in risk, and nearly 70% of new stenoses occurred in patients with baseline single-vessel disease (hazard ratio, 3.86 [95% CI, 3.69-4.04]). Coronary artery segments in patients with no baseline risk factors had a progression rate of 0.6% and incidence rate of 0.36 (95% CI, 0.34-0.39), increasing to 8.1% and 4.01 (95% CI, 3.89-4.14) per 1000 segment-years, respectively, in patients with ≥4 risk factors. The prognostic impact of risk factors on stenosis progression was greatest in younger patients and women. Conclusions Coronary atherosclerosis progressed slowly but more frequently in the left coronary artery in men and in the presence of traditional risk factors. Coronary artery segments in patients without risk factors had little or no risk of stenosis progression, and the relative impact of risk factors appears to be of greater importance in younger patients and women. These findings help in the understanding the long-term course of coronary atherosclerosis.

Pretreatment with heparin in patients with ST-segment elevation myocardial infarction: a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

BACKGROUND: Unfractionated heparin (UFH) is frequently administered before percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). AIMS: The aim of the study was to investigate if pretreatment with UFH prior to arrival at the catheterisation laboratory affects coronary artery occlusion, mortality, and in-hospital major bleeding in patients with STEMI undergoing PCI. METHODS: Patients with a first STEMI event undergoing PCI between 2008 and 2016 were extracted from the Swedish Coronary Angiography and Angioplasty Registry. Risk ratios for UFH pretreatment versus no pretreatment regarding coronary artery occlusion at presentation in the catheterisation laboratory, 30-day mortality, and bleeding were obtained using adjusted Poisson regression models with robust standard errors. Analyses of propensity score (PS)-matched groups were performed to obtain absolute risk differences. RESULTS: In all, 41,631 patients were included, 16,026 (38%) with and 25,605 (62%) without UFH pretreatment. Adjusted risk ratios were 0.89 (95% confidence interval [CI]: 0.87 to 0.90) for coronary artery occlusion, 0.87 (0.77 to 0.99) for mortality, and 1.01 (0.86 to 1.18) for bleeding. In the PS-matched analyses, the absolute risk differences were -0.087 (-0.074 to -0.099) for coronary artery occlusion, -0.011 (-0.017 to -0.0041) for mortality, and 0 (-0.0052 to 0.0052) for bleeding. CONCLUSIONS: Pretreatment with UFH was associated with a reduction in coronary artery occlusion among patients with STEMI, with a number needed to treat (NNT) of 12, without increasing the risk of major in-hospital bleeding. Regarding mortality, a reduction was found with UFH pretreatment, with an NNT of 94, but this effect was not robust over all sensitivity analyses and residual confounding cannot be excluded.

Rationale and design of switch Swedeheart: A registry-based, stepped-wedge, cluster-randomized, open-label multicenter trial to compare prasugrel and ticagrelor for treatment of patients with acute coronary syndrome.

BACKGROUND: European treatment guidelines recommend prasugrel over ticagrelor for treating patients with non-ST-elevation acute coronary syndrome (ACS), prompting several Swedish administrative regions to transition from ticagrelor to prasugrel as the preferred treatment for patients with ACS. We aim to systematically evaluate this transition to determine the relative efficacy of prasugrel versus ticagrelor in a real-world cohort of patients with ACS. STUDY DESIGN AND OBJECTIVES: The SWITCH SWEDEHEART trial is a prospective, multicenter, open-label, cross-sectional, stepped-wedge cluster-randomized clinical trial, in which administrative regions in Sweden will constitute the clusters. At the start of the study, all clusters will use ticagrelor as the P2Y12 inhibitor drug of choice for ACS. The order in which the clusters will implement the transition from ticagrelor to prasugrel will be randomly assigned. Every 9 months, 1 cluster will switch from ticagrelor to prasugrel as the P2Y12 inhibitor of choice for patients with ACS. The primary endpoint is the composite 1-year rate of the death, stroke, or myocardial infarction. CONCLUSIONS: The SWITCH SWEDEHEART study will provide an extensive randomized comparison between ticagrelor and prasugrel. Novel therapies are frequently costly and supported by evidence from few or small studies, and systematic evaluation after the introduction is rare. This study will establish an important standard for introducing and evaluating the effects of health care changes within our societies.

5-Year Outcomes of PCI Guided by Measurement of Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve.

BACKGROUND: Instantaneous wave-free ratio (iFR) is a coronary physiology index used to assess the severity of coronary artery stenosis to guide revascularization. iFR has previously demonstrated noninferior short-term outcome compared to fractional flow reserve (FFR), but data on longer-term outcome have been lacking. OBJECTIVES: The purpose of this study was to investigate the prespecified 5-year follow-up of the primary composite outcome of all-cause mortality, myocardial infarction, and unplanned revascularization of the iFR-SWEDEHEART trial comparing iFR vs FFR in patients with chronic and acute coronary syndromes. METHODS: iFR-SWEDEHEART was a multicenter, controlled, open-label, registry-based randomized clinical trial using the Swedish Coronary Angiography and Angioplasty Registry for enrollment. A total of 2,037 patients were randomized to undergo revascularization guided by iFR or FFR. RESULTS: No patients were lost to follow-up. At 5 years, the rate of the primary composite endpoint was 21.5% in the iFR group and 19.9% in the FFR group (HR: 1.09; 95% CI: 0.90-1.33). The rates of all-cause death (9.4% vs 7.9%; HR: 1.20; 95% CI: 0.89-1.62), nonfatal myocardial infarction (5.7% vs 5.8%; HR: 1.00; 95% CI: 0.70-1.44), and unplanned revascularization (11.6% vs 11.3%; HR: 1.02; 95% CI: 0.79-1.32) were also not different between the 2 groups. The outcomes were consistent across prespecified subgroups. CONCLUSIONS: In patients with chronic or acute coronary syndromes, an iFR-guided revascularization strategy was associated with no difference in the 5-year composite outcome of death, myocardial infarction, and unplanned revascularization compared with an FFR-guided revascularization strategy. (Evaluation of iFR vs FFR in Stable Angina or Acute Coronary Syndrome [iFR SWEDEHEART]; NCT02166736).

Calcium Load in the Aortic Valve, Aortic Root, and Left Ventricular Outflow Tract and the Risk for a Periprocedural Stroke.

Background: Periprocedural stroke during transcatheter aortic valve implantation is a rare but devastating complication. The calcified aortic valve is the most likely source of the emboli in a periprocedural stroke. The total load and distribution of calcium in the leaflets, aortic root, and left ventricular outflow tract varies from patient to patient. Consequently, there could be patterns of calcification that are associated with a higher risk of stroke. This study aimed to explore whether the pattern of calcification in the left ventricular outflow tract, annulus, aortic valve, and ascending aorta can be used to predict a periprocedural stroke. Methods: Among the 3282 consecutive patients who received a transcatheter aortic valve implantation in the native valve in Sweden from 2014 to 2018, we identified 52 who had a periprocedural stroke. From the same cohort, a control group of 52 patients was constructed by propensity score matching. Both groups had one missing cardiac computed tomography, and 51 stroke and 51 control patients were blindly reviewed by an experienced radiologist. Results: The groups were well balanced in terms of demographics and procedural data. Of the 39 metrics created to describe calcium pattern, only one differed between the groups. The length of calcium protruding above the annulus was 10.6 mm (interquartile range 7-13.6) for patients without stroke and 8 mm (interquartile range 3-10) for stroke patients. Conclusions: This study could not find any pattern of calcification that predisposes for a periprocedural stroke.

Causes, pattern, predictors, and prognostic implications of new hospitalizations after transcatheter aortic valve implantation: a long-term nationwide observational study.

AIMS: The aim of this study was to investigate the pattern, causes, and predictors of all new hospitalizations in patients who underwent transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: The nationwide Swedish TAVI registry was merged with other mandatory healthcare registries, which enabled the analysis of all TAVI procedures, new hospital admissions, and death between the years 2008 and 2017. A total of 2821 patients underwent TAVI with a mean of 2.5 hospitalizations during a mean follow-up of 2.2 years. Hospitalizations were associated with worse prognosis. Heart failure (HF) was the most common cause of hospitalization with 19% having at least one hospitalization due to HF causing, 16% of all-cause admissions, and 50% of cardiovascular admissions. Male gender, age >90 years, high Charlson Comorbidity Index, atrial fibrillation, present neurologic disease, severe renal impairment, peripheral vascular disease, New York Heart Association class IV, mild or moderate mean aortic valve gradients, and pulmonary hypertension were associated with an increased risk for all-cause hospitalizations or death. For cardiovascular hospitalization or death, the pattern was similar, with the addition of impaired systolic left ventricular function as a predictor. CONCLUSION: Multiple hospitalizations after TAVI are common and are often caused by HF. Reducing the rate of HF hospitalizations is important to mitigate the burden on the healthcare system due to new hospitalizations after TAVI.

Development and validation of an artificial neural network algorithm to predict mortality and admission to hospital for heart failure after myocardial infarction: a nationwide population-based study.

BACKGROUND: Patients have an estimated mortality of 15-20% within the first year following myocardial infarction and one in four patients who survive myocardial infarction will develop heart failure, severely reducing quality of life and increasing the risk of long-term mortality. We aimed to establish the accuracy of an artificial neural network (ANN) algorithm in predicting 1-year mortality and admission to hospital for heart failure after myocardial infarction. METHODS: In this nationwide population-based study, we used data for all patients admitted to hospital for myocardial infarction and discharged alive from a coronary care unit in Sweden (n=139 288) between Jan 1, 2008, and April 1, 2017, from the Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) nationwide registry; these patients were randomly divided into training (80%) and testing (20%) datasets. We developed an ANN using 21 variables (including age, sex, medical history, previous medications, in-hospital characteristics, and discharge medications) associated with the outcomes of interest with a back-propagation algorithm in the training dataset and tested it in the testing dataset. The ANN algorithm was then validated in patients with incident myocardial infarction enrolled in the Western Denmark Heart Registry (external validation cohort) between Jan 1, 2008, and Dec 31, 2016. The predictive ability of the model was evaluated using area under the receiver operating characteristic curve (AUROC) and Youden's index was established as a means of identifying an empirical dichotomous cutoff, allowing further evaluation of model performance. FINDINGS: 139 288 patients who were admitted to hospital for myocardial infarction in the SWEDEHEART registry were randomly divided into a training dataset of 111 558 (80%) patients and a testing dataset of 27 730 (20%) patients. 30 971 patients with myocardial infarction who were enrolled in the Western Denmark Heart Registry were included in the external validation cohort. A first event, either all-cause mortality or admission to hospital for heart failure 1 year after myocardial infarction, occurred in 32 308 (23·2%) patients in the testing and training cohorts only. For 1-year all-cause mortality, the ANN had an AUROC of 0·85 (95% CI 0·84-0·85) in the testing dataset and 0·84 (0·83-0·84) in the external validation cohort. The AUROC for admission to hospital for heart failure within 1 year was 0·82 (0·81-0·82) in the testing dataset and 0·78 (0·77-0·79) in the external validation dataset. With an empirical cutoff the ANN algorithm correctly classified 73·6% of patients with regard to all-cause mortality and 61·5% of patients with regard to admission to hospital for heart failure in the external validation cohort, ruling out adverse outcomes with 97·1-98·7% probability in the external validation cohort. INTERPRETATION: Identifying patients at a high risk of developing heart failure or death after myocardial infarction could result in tailored therapies and monitoring by the allocation of resources to those at greatest risk. FUNDING: The Swedish Heart and Lung Foundation, Swedish Scientific Research Council, Swedish Foundation for Strategic Research, Knut and Alice Wallenberg Foundation, ALF Agreement on Medical Education and Research, Skane University Hospital, The Bundy Academy, the Märta Winkler Foundation, the Anna-Lisa and Sven-Eric Lundgren Foundation for Medical Research.

Bivalirudin Versus Heparin Monotherapy in ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: Bivalirudin was not superior to unfractionated heparin in patients with myocardial infarction (MI) treated with percutaneous coronary intervention and no planned use of GPI (glycoprotein IIb/IIIa inhibitors) in contemporary clinical practice of radial access and potent P2Y12-inhibitors in the VALIDATE-SWEDEHEART randomized clinical trial (Bivalirudin Versus Heparin in STEMI and NSTEMI Patients on Modern Antiplatelet Therapy-Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry). METHODS: In this prespecified separately powered subgroup analysis, we included patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with the primary composite end point of all-cause death, MI, or major bleeding event within 180 days. RESULTS: Among the 6006 patients enrolled in the trial, 3005 patients with ST-segment-elevation MI were randomized to receive bivalirudin or heparin. The mean age was 66.8 years. According to protocol recommendations, 87% were treated with potent oral P2Y12-inhibitors before start of angiography and radial access was used in 90%. GPI was used in 51 (3.4%) and 74 (4.9%) of patients randomized to receive bivalirudin and heparin, respectively. The primary end point occurred in 12.5% (187 of 1501) and 13.0% (196 of 1504; hazard ratio [HR], 0.95 [95% CI, 0.78-1.17], P=0.64) with consistent results in all major subgroups. All-cause death occurred in 3.9% versus 3.9% (HR, 1.00 [0.70-1.45], P=0.98), MI in 1.7% versus 2.2% (HR, 0.76 [0.45-1.28], P=0.30), major bleeding in 8.3% versus 8.0% (HR, 1.04 [0.81-1.33], P=0.78), and definite stent thrombosis in 0.5% versus 1.3% (HR, 0.42 [0.18-0.96], P=0.04). CONCLUSIONS: In patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with radial access and receiving current recommended treatments with potent P2Y12-inhibitors rate of the composite of all-cause death, MI, or major bleeding was not lower in those randomized to receive bivalirudin as compared with heparin. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.

Instantaneous wave-free ratio compared with fractional flow reserve in PCI: A cost-minimization analysis.

BACKGROUND: Coronary physiology is a routine diagnostic tool when assessing whether coronary revascularization is indicated. The iFR-SWEDEHEART trial demonstrated similar clinical outcomes when using instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) to guide revascularization. The objective of this analysis was to assess a cost-minimization analysis of iFR-guided compared with FFR-guided revascularization. METHODS: In this cost-minimization analysis we used a decision-tree model from a healthcare perspective with a time-horizon of one year to estimate the cost difference between iFR and FFR in a Nordic setting and a United States (US) setting. Treatment pathways and health care utilizations were constructed from the iFR-SWEDEHEART trial. Unit cost for revascularization and myocardial infarction in the Nordic setting and US setting were derived from the Nordic diagnosis-related group versus Medicare cost data. Unit cost of intravenous adenosine administration and cost per stent placed were based on the average costs from the enrolled centers in the iFR-SWEDEHEART trial. Deterministic and probabilistic sensitivity analyses were carried out to test the robustness of the result. RESULTS: The cost-minimization analysis demonstrated a cost saving per patient of $681 (95% CI: $641 - $723) in the Nordic setting and $1024 (95% CI: $934 - $1114) in the US setting, when using iFR-guided compared with FFR-guided revascularization. The results were not sensitive to changes in uncertain parameters or assumptions. CONCLUSIONS: IFR-guided revascularization is associated with significant savings in cost compared with FFR-guided revascularization.

Validation of the 4-Item PRECISE-DAPT Score: A SWEDEHEART Study.

Background The Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score has been shown to predict out-of-hospital major bleeding after myocardial infarction treated with percutaneous coronary intervention and dual antiplatelet therapy (DAPT). However, large validation studies have been scarce and the discriminative ability for patients with a preexisting bleeding risk factor (elderly, underweight, women, anemia, kidney dysfunction, or cancer) in a real-world setting is unknown. Methods and Results Patients undergoing percutaneous coronary intervention for myocardial infarction between 2008 and 2017 were included from the SWEDEHEART (Swedish Web System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry (n=66 295). The predictive value of the PRECISE-DAPT score for rehospitalization with major bleeding during dual antiplatelet therapy was evaluated using receiver operating characteristic analyses. A high PRECISE-DAPT score (≥25; n=13 894) was associated with increased risk of major bleeding (3.9% versus 1.8%; hazard ratio [HR], 2.2; 95% CI, 2.0-2.5; P<0.001) compared with a non-high score (<25; n=52 401). The score demonstrated a c-statistic of 0.64 (95% CI, 0.63-0.66). The discriminative ability of the score to further stratify bleeding risk in patients with preexisting bleeding risk factors was poor, especially in patients who are elderly (c-statistic=0.57; 95% CI, 0.55-0.60) or underweight (c-statistic=0.56; 95% CI, 0.51-0.61), for whom a non-high PRECISE-DAPT score was associated with similar bleeding risk as a high PRECISE-DAPT score in the general myocardial infarction population. Conclusions In this nationwide population-based study, the PRECISE-DAPT score performed moderately in the general myocardial infarction population and poorly in patients with preexisting bleeding risk factors, where its usefulness seems limited.

Clinical Impact of Intraprocedural Stent Thrombosis During Percutaneous Coronary Intervention in Patients Treated With Potent P2Y12 inhibitors - a VALIDATE-SWEDEHEART Substudy.

Background The clinical importance of intraprocedural stent thrombosis (IPST) during percutaneous coronary intervention in the contemporary era of potent oral P2Y12 inhibitors is not established. The aim of this study was to assess IPST and its association with clinical outcome in patients with myocardial infarction undergoing percutaneous coronary intervention with contemporary antithromboticmedications. Methods and Results The VALIDATE-SWEDEHEART study (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial) included 6006 patients with myocardial infarction, treated with potent P2Y12 inhibitors during percutaneous coronary intervention. IPST, defined as a new or worsening thrombus related to a stent deployed during the procedure, was reported by the interventional cardiologist in 55 patients (0.9%) and was significantly associated with ST-segment elevation myocardial infarction presentation, longer stents, bailout glycoprotein IIb/IIIa inhibitors, and final Thrombolysis in Myocardial Infarction flow <3. The primary composite end point included cardiovascular death, myocardial infarction, out-of-laboratory definite stent thrombosis and target vessel revascularization within 30 days. Secondary end points were major bleeding and the individual components of the primary composite end point. Patients with versus without IPST had significantly higher rates of the primary composite end point (20.0% versus 4.4%), including higher rates of cardiovascular death, target vessel revascularization, and definite stent thrombosis, but not myocardial infarction or major bleeding. By multivariable analysis, IPST was independently associated with the primary composite end point (hazard ratio, 3.82; 95% CI, 2.05-7.12; P<0.001). Conclusions IPST is a rare but dangerous complication during percutaneous coronary intervention, independently associated with poor prognosis, even in the current era of potent antiplatelet agents. Future treatment studies are needed to reduce the rate of IPST and to improve the poor outcome among these patients. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.