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Aims Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function. Methods and results Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg–/– mice). In 9- to 10-week-old hUgcg–/– mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg–/– mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to β-adrenergic stimulation was reduced in cardiomyocytes from hUgcg–/– mice and that Ugcg knockdown suppressed the internalization and trafficking of β1-adrenergic receptors. Conclusions Our findings suggest that cardiac glycosphingolipids are required to maintain β-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function., Graphical Abstract Cardiac glycosphingolipids are required to maintain β-adrenergic signaling and contractile capacity in cardiomyocytes and to preserve normal heart function.

Objective To evaluate the long-term efficacy of three currently available drug coated balloons (DCB) for the treatment of de-novo coronary lesions. Methods This was a retrospective analysis of prospectively collected data from the Swedish Coronary Angiography and Angioplasty Registry. Between 2009 and 2017, three currently available DCB brands used in the treatment of de novo lesions were included. Outcomes were clinically driven restenosis and target lesion thrombosis (TLT) (per device) and major adverse cardiac events (MACE) including death, myocardial infarction or target vessel revascularization (per patient) at 4 years. Multivariable Cox regression models were used to adjust for differences. Results We included 6715 lesions treated with DCBs, 4483 SeQuent® Please (S-DCB), 1071 IN.PACT Falcon (I-DCB) and 1161 Pantera® Lux (P-DCB), in 5670 patients. The mean DCB diameter was 2.4 mm. Bailout stenting occurred in 6.7% of lesions. Angiographic success was 98.5%. The overall cumulative rate of restenosis was 5.5% (299 events). The risk for reported restenosis did not significantly differ between I-DCB vs S-DCB, adjusted hazard ratio (aHR) 0.96; 95% confidence interval (CI) 0.69–1.34, P-DCB vs S-DCB aHR 0.88; 95% CI 0.63–1.23 and I-DCB vs P-DCB aHR 1.10; 95% CI 0.72–1.68. The cumulative risk for TLT was 0.8% in all three DCBs. The risk for MACE or individual components of MACE did not differ between the three patient-groups. Conclusion In de novo coronary lesions, we found comparable long-term efficacy with three currently available DCB brands. DCB angioplasty was feasible with low risk for long-term restenosis and TLT.

Aims The risk of life‐threatening ventricular arrhythmias (LTVA) has been reported to be lower in Takotsubo syndrome (TS) compared with ST‐elevation myocardial infarction (STEMI). However, the extent to which these differences relate to the fact that most patients with TS are women (who have a lower risk of LTVA) and a relatively larger proportion of patients with STEMI are men is incompletely understood. We aimed to investigate the risk of LTVA or death in sex‐matched and age‐matched patients with TS, anterior STEMI, and non‐anterior STEMI. Methods and results We systematically reviewed the charts of all patients with TS who were treated at Sahlgrenska University Hospital (Gothenburg, Sweden) between 2008 and 2019. A total of 155 patients with confirmed TS (according to the European Society of Cardiology diagnostic criteria for TS) were sex‐matched and age‐matched 1:1:1 to patients with anterior and non‐anterior STEMI. Baseline characteristics and in‐hospital outcomes were recorded directly from the patient charts for all patients, and all admission electrocardiographs were analysed. The primary outcome was the composite of death or LTVA [defined as sustained ventricular tachycardia (>30 s) or ventricular fibrillation] within 72 h. The risk of LTVA or death within 72 h after admission was considerably lower in TS (2.6%) vs. anterior STEMI (14%; P = 0.002) and non‐anterior STEMI (9.0%; P = 0.02), despite similar or greater risks of acute heart failure, and similar risks of cardiogenic shock. Compared with STEMI, TS was associated with a lower risk of sustained and non‐sustained ventricular tachycardia and ventricular fibrillation. Conclusions In a predominantly female age‐matched and sex‐matched cohort of patients with TS, anterior STEMI, and non‐anterior STEMI, the adjusted risk of in‐hospital LTVA or death was considerably lower in TS compared with STEMI, despite similar or greater risk of acute heart failure and similar risk of cardiogenic shock.

Aims: Percutaneous coronary intervention (PCI) improves outcomes in non-ST elevation acute coronary syndromes (NSTE-ACSs). Octogenarians, however, were underrepresented in the pivotal trials. This study aimed to assess the effect of PCI in patients ≥80 years old. Methods and results: We used data from the SWEDEHEART registry for all hospital admissions at eight cardiac care centres within Västra Götaland County. Consecutive patients ≥80 years old admitted for NSTE-ACS between January 2000 and December 2011 were included. We performed instrumental variable analysis with propensity score. The primary endpoint was all-cause mortality at 30 days and one year after index hospitalization. During the study period 5200 patients fulfilled the inclusion criteria. In total, 586 (11.2%) patients underwent PCI, the remaining 4613 patients were treated conservatively. Total mortality at 30 days was 19.4% (1007 events) and 39.4% (1876 events) at one year. Thirty-day mortality was 20.7% in conservatively treated patients and 8.5% in the PCI group (adjusted odds ratio 0.34; 95% confidence interval 0.12–0.97, p = 0.044). One-year mortality was 42.1% in the conservatively treated group and 16.3% in the PCI group (adjusted odds ratio 0.97; 95% confidence interval 0.36–2.51, p = 0.847). Conclusions: PCI in octogenarians with NSTE-ACS was associated with a lower risk of mortality at 30 days. However, this survival benefit was not sustained during the entire study-period of one-year.

Objectives The aim of this study was to determine the prognostic value of fractional flow reserve (FFR) in non-infarct-related arteries (IRAs) in ST-segment elevation myocardial infarction (MI). Background Patients with ST-segment elevation MI often present with multivessel disease. The treatment of non-IRAs is debated. The applicability of FFR has not been widely proved. Methods Outcomes were analyzed in all patients in the Compare-Acute (Comparison Between FFR Guided Revascularization Versus Conventional Strategy in Acute STEMI Patients With MVD) trial in whom, after successful primary percutaneous coronary intervention, non-IRAs were interrogated using FFR and treated medically. The treating cardiologist was blinded to the FFR value. The primary endpoint was the composite of cardiovascular mortality, target vessel–related (non-IRA with FFR measurement at primary percutaneous coronary intervention) nonfatal MI, and target vessel revascularization: major adverse cardiac events (MACE) at 24 months. Results A total of 751 patients (963 vessels) were included. Target non-IRAs with MACE had lower FFR compared with those without (0.78 vs. 0.84, respectively; p Conclusions In patients with ST-segment elevation MI with multivessel disease, FFR measured in the medically treated non-IRA immediately after successful primary percutaneous coronary intervention shows a nonlinear and inverse risk continuum of MACE. Importantly, worsening prognosis is demonstrated around the cutoff of 0.80.

Background Takotsubo syndrome (TS) is a life-threatening acute heart failure syndrome. However, little is known about risk factors for worse outcomes in TS and no high-risk ECG criteria have been defined. We sought to identify ECG predictors of life-threatening in-hospital complications in TS. Method and result Using the nationwide Swedish Angiography and Angioplasty Registry (SCAAR) we obtained data on all consecutive patients undergoing coronary angiography at Sahlgrenska University Hospital between June 2008 and February 2019. For all patients with TS we conducted in-depth chart reviews to confirm the TS diagnosis. For those with confirmed TS we then evaluated all ECGs obtained during the index hospitalization. The primary endpoint was the occurrence of in-hospital major adverse cardiac event (MACE), defined as the composite of death, ventricular tachycardia or fibrillation (VT/VF), or atrioventricular block ≥2 or asystole ≫10 s. We identified 215 patients with TS (mean age 69 ± 13 years; 93% women). MACE occurred in 34 patients (16%), of whom 20 had VT/VF (9,3%). Patients with MACE were less likely than those without MACE to have sinus rhythm (85% versus 96%, p = 0.025) or T-wave inversion (29% versus 51%, p = 0.025). After propensity score adjustment T-wave inversion was independently associated with lower MACE risk (adjusted odds ratio [AdjOR] 0.28, 95% confidence interval [CI] 0.10–0.76, p = 0.012) and VT/VF (AdjOR 0.24, 95% CI 0.06–0.94, p = 0.041). Conclusion T-wave inversion is common in TS and is associated with lower risk of MACE, driven by a lower risk of VT/VF.

Aims Left ventricular (LV) dysfunction can be triggered by non‐cardiac disease, such as sepsis, hypoxia, major haemorrhage, or severe stress (Takotsubo syndrome), but its clinical importance is not established. In this study, we evaluate the incidence and impact on mortality of LV dysfunction associated with critical illness. Methods and results In this single‐centre, observational study, consecutive patients underwent an echocardiographic examination within 24 h of intensive care unit (ICU) admission. LV systolic dysfunction was defined as an ejection fraction (EF)

Aims To compare coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) for treatment of patients with heart failure due to ischaemic heart disease. Methods and results We analysed all-cause mortality following CABG or PCI in patients with heart failure with reduced ejection fraction and multivessel disease (coronary artery stenosis >50% in ≥2 vessels or left main) who underwent coronary angiography between 2000 and 2018 in Sweden. We used a propensity score-adjusted logistic and Cox proportional-hazards regressions and instrumental variable model to adjust for known and unknown confounders. Multilevel modelling was used to adjust for the clustering of observations in a hierarchical database. In total, 2509 patients (82.9% men) were included; 35.8% had diabetes and 34.7% had a previous myocardial infarction. The mean age was 68.1 ± 9.4 years (47.8% were >70 years old), and 64.9% had three-vessel or left main disease. Primary designated therapy was PCI in 56.2% and CABG in 43.8%. Median follow-up time was 3.9 years (range 1 day to 10 years). There were 1010 deaths. Risk of death was lower after CABG than after PCI [odds ratio (OR) 0.62; 95% confidence interval (CI) 0.41–0.96; P = 0.031]. The risk of death increased linearly with quintiles of hospitals in which PCI was the preferred method for revascularization (OR 1.27, 95% CI 1.17–1.38, Ptrend < 0.001). Conclusion In patients with ischaemic heart failure, long-term survival was greater after CABG than after PCI., Graphical Abstract Study flowchart, time-to-first-event curves through 10-year follow-up and risk-estimate for the primary endpoint – all – cause mortality.

Aims Takotsubo syndrome (TTS) is an acute potentially reversible cardiac syndrome characterized by variable regional myocardial akinesia that cannot be attributed to a culprit coronary artery occlusion. TTS is an important differential diagnosis of acute heart failure where brain natriuretic peptides are elevated. Sacubitril/valsartan is a novel and effective pharmacological agent for the treatment of patients with heart failure. Our aim was to explore whether treatment with sacubitril/valsartan could prevent isoprenaline‐induced takotsubo‐like phenotype in rats. Methods and results A total number of 186 Sprague–Dawley male rats were randomized to receive pretreatment with water (CONTROL, n = 62), valsartan (VAL, n = 62), or sacubitril/valsartan (SAC/VAL, n = 62) before receiving isoprenaline for induction of TTS. We recorded heart rate and blood pressure invasively. Cardiac morphology and function were evaluated by high‐resolution echocardiography 90 min after the administration of isoprenaline. We documented the survival rate at the time of echocardiography. Compared with the CONTROL group, the SAC/VAL group had less pronounced TTS‐like cardiac dysfunction and lower mortality rate, while the VAL group did not differ. Heart rate and blood pressure were not significantly different between the groups. Analysis of cardiac lipids was performed with mass spectrometry. The VAL and SAC/VAL groups had significantly higher levels of lysophosphatidylcholine (LPC), in particular LPC 18:1 and LPC 16:0. Conclusions Pretreatment with sacubitril/valsartan but not with valsartan reduces mortality and attenuates isoprenaline‐induced apical akinesia in the TTS‐like model in rats. Sacubitril/valsartan could be a potential treatment option in patients with TTS in humans.

Inger Haraldsson,1,2 Li-Ming Gan,1–3 Sara Svedlund,1,4 Kristina Torngren,5 Helena U Westergren,6 Björn Redfors,1,2 Maria Lagerström-Fermér,3 Oskar Angerås,1,2 Truls Råmunddal,1,2 Petur Petursson,1,2 Jacob Odenstedt,1,2 Per Albertsson,1,2 David Erlinge,5 Elmir Omerovic1,21Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden; 3Early Clinical Development, IMED Biotech Unit, AstraZeneca R&D, Gothenburg, Sweden; 4Department of Clinical Physiology, Sahlgrenska University Hospital, Gothenburg, Sweden; 5Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden; 6Precision Medicine and Genomics, IMED Biotech Unit, AstraZeneca R&D, Gothenburg, SwedenCorrespondence: Elmir OmerovicDepartment of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Bruna stråket 16, 41345 Gothenburg, SwedenTel +46 31 342 2950Fax +46 3 182 3762Email elmir@wlab.gu.seBackground: Survivors of myocardial infarction (MI) are at high risk of new major adverse cardiovascular events (MACE). Coronary flow reserve (CFR) is a strong and independent predictor of MACE. Understanding the prevalence of impaired CFR in this patient group and identifying risk markers for impaired CFR are important steps in the development of personalized and targeted treatment for high-risk individuals with prior MI.Methods: PROFLOW is a prospective, exploratory, cross-sectional open study. We used information from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) to identify high-risk patients with a history of type-1 MI. We measured CFR non-invasively in a left anterior descending artery (LAD) using transthoracic Doppler echocardiography. Coronary flow velocity was measured at rest and at maximal flow after induction of hyperemia by intravenous infusion of adenosine (140μg/kg/min). Independent predictors of CFR were assessed with multiple linear regression.Results: We included 619 patients. The median age was 69 (IQR 65–73), and 114 (18.4%) were women. Almost one-half of the patients, 285 (46.0%) had the multi-vessel disease, and 147 (23.7%) were incompletely revascularized. The majority were on optimal standard treatment eg ASA (93.1%), statins (90.0%), ACEI/ARB (82.6%) and beta-blockers (80.8%). The majority, 547 (88.4%) had no angina pectoris, and 572 (92.2%) were in NYHA class I. Evaluation of CFR was possible in 611 (98.7%) patients. Mean CFR was 2.74 (±0.79 (mean±SD)). A substantial number of patients (39.7%) had CFR ≤2.5. In a multiple linear regression model age, dyslipidemia, smoking, hypertension, body mass index, incomplete revascularization, and treatment with angiotensin receptor blockers were independent predictors of CFR.Conclusion: In this high-risk group of patients with prior MI, the prevalence of impaired CFR was high. Further risk stratification with CFR in addition to traditional cardiovascular risk factors may improve predictive accuracy for future MACE in this patient population.Keywords: coronary flow reserve, myocardial infarction, secondary prevention, Doppler echocardiography, prognosis

Aims Heparin is the preferred choice of anticoagulant in percutaneous coronary intervention (PCI) for acute myocardial infarction (MI). An established dosage of heparin has not yet been determined, but treatment may be optimized through monitoring of activated clotting time (ACT). The aim of this study was to determine the relationship between heparin dose or ACT with a composite outcome of death, MI, or bleeding using data from the registry-based, randomized, controlled, and open-label VALIDATE-SWEDEHEART trial, although patients were not randomized to heparin dose in this substudy. Methods and results Patients with MI undergoing PCI and receiving treatment with a potent P2Y12-inhibitor and anticoagulation with heparin, without the planned use of glycoprotein IIb/IIIa inhibitor (GPI), were enrolled in this substudy. The primary endpoint was a composite endpoint of death, MI, and bleeding at 30 days. The individual components and stent thrombosis were analysed separately. We divided patients into groups according to the initial dose of unfractionated heparin during PCI (100 U/kg) or ACT (ACT 350 s) as well as investigating them as continuous variables in Cox proportional hazards models using univariable and multivariable analyses. No major differences were noted between heparin stratified in groups (P = 0.22) or heparin as a continuous variable in relation to the primary composite endpoint hazard ratio (HR) 1.0 confidence interval (CI) (0.99–1.01) for heparin dose/kg. No differences were found between ACT stratified in groups (P = 0.453) or ACT in seconds HR 1.0 CI (0.99–1.00) regarding the primary endpoint. The individual components of death, MI, major bleeding, and stent thrombosis were not significantly different across heparin doses or ACT levels either. Conclusion We found no association between heparin dose or ACT levels and death, MI bleeding complications, or stent thrombosis. Therefore, there is no strong support for a specific heparin dose or mandatory ACT monitoring in patients treated with potent P2Y12-inhibitors with no planned GPI.

Background: Premature coronary artery disease (CAD) is a major cause of mortality and morbidity. Increased low-density lipoprotein-cholesterol (LDL-C) level is a major risk factor for CAD and thus the main target for its prevention. Familial Hypercholesterolemia (FH) is a genetic inherited disorder characterized by high LDL-C, and subsequent premature CAD development. Early drug treatment with lipid-lowering medications in FH prevents cardiovascular disease onset. The FH prevalence in the Northern European general population is 0.3%, and it is estimated that it explains 20% of premature CAD cases in individuals with familial clustering. Despite the wide number of papers showing the prevalence of clinical FH in cardiovascular disease, the prevalence of genetic FH in individuals with premature CAD is not yet well known. Here, we examined the prevalence of genetically determined FH in individuals with premature CAD. Patients and methods: 66 patients who underwent coronary angiography with suspected premature acute coronary syndrome (age

This position paper focusses on the pathophysiology, diagnosis and management of women diagnosed with a cardiomyopathy, or at risk of heart failure (HF), who are planning to conceive or present with (de novo or previously unknown) HF during or after pregnancy. This includes the heterogeneous group of heart muscle diseases such as hypertrophic, dilated, arrhythmogenic right ventricular and non-classified cardiomyopathies, left ventricular non-compaction, peripartum cardiomyopathy, Takotsubo syndrome, adult congenital heart disease with HF, and patients with right HF. Also, patients with a history of chemo-/radiotherapy for cancer or haematological malignancies need specific pre-, during and post-pregnancy assessment and counselling. We summarize the current knowledge about pathophysiological mechanisms, including gene mutations, clinical presentation, diagnosis, and medical and device management, as well as risk stratification. Women with a known diagnosis of a cardiomyopathy will often require continuation of drug therapy, which has the potential to exert negative effects on the foetus. This position paper assists in balancing benefits and detrimental effects. ispartof: EUROPEAN JOURNAL OF HEART FAILURE vol:23 issue:4 pages:527-540 ispartof: location:England status: published

Background Near-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs). Methods PROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065. Findings Between June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17 women, 745 [83 men; median age 63 [IQR 55-70] years). Median follow-up was 3.7 (IQR 3.0-4.4) years. Adverse events within 4 years occurred in 112 (13.2 951.0-15.6) of 898 patients, with 66 (8.0 95.2-10.0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46.9[SD 15.9]). Highly lipidic lesions (851 [24 of 3500 lesions, present in 520 [59 of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2.27, 95.25-4.13) and nonculprit lesion-specific MACEs (7.83, 4.12-14.89). Large plaque burden (787 [22 of 3629 lesions, present in 530 [59 of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7.095.0-10.0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13.295.4-17.6). Interpretation Combined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes. Copyright (C) 2021 Elsevier Ltd. All rights reserved. BackgroundNear-infrared spectroscopy (NIRS) and intravascular ultrasound are promising imaging modalities to identify non-obstructive plaques likely to cause coronary-related events. We aimed to assess whether combined NIRS and intravascular ultrasound can identify high-risk plaques and patients that are at risk for future major adverse cardiac events (MACEs).MethodsPROSPECT II is an investigator-sponsored, multicentre, prospective natural history study done at 14 university hospitals and two community hospitals in Denmark, Norway, and Sweden. We recruited patients of any age with recent (within past 4 weeks) myocardial infarction. After treatment of all flow-limiting coronary lesions, three-vessel imaging was done with a combined NIRS and intravascular ultrasound catheter. Untreated lesions (also known as non-culprit lesions) were identified by intravascular ultrasound and their lipid content was assessed by NIRS. The primary outcome was the covariate-adjusted rate of MACEs (the composite of cardiac death, myocardial infarction, unstable angina, or progressive angina) arising from untreated non-culprit lesions during follow-up. The relations between plaques with high lipid content, large plaque burden, and small lumen areas and patient-level and lesion-level events were determined. This trial is registered with ClinicalTrials.gov, NCT02171065.FindingsBetween June 10, 2014, and Dec 20, 2017, 3629 non-culprit lesions were characterised in 898 patients (153 [17%] women, 745 [83%] men; median age 63 [IQR 55–70] years). Median follow-up was 3·7 (IQR 3·0–4·4) years. Adverse events within 4 years occurred in 112 (13·2%, 95% CI 11·0–15·6) of 898 patients, with 66 (8·0%, 95% CI 6·2–10·0) arising from 78 untreated non-culprit lesions (mean baseline angiographic diameter stenosis 46·9% [SD 15·9]). Highly lipidic lesions (851 [24%] of 3500 lesions, present in 520 [59%] of 884 patients) were an independent predictor of patient-level non-culprit lesion-related MACEs (adjusted odds ratio 2·27, 95% CI 1·25–4·13) and non-culprit lesion-specific MACEs (7·83, 4·12–14·89). Large plaque burden (787 [22%] of 3629 lesions, present in 530 [59%] of 898 patients) was also an independent predictor of non-culprit lesion-related MACEs. Lesions with both large plaque burden by intravascular ultrasound and large lipid-rich cores by NIRS had a 4-year non-culprit lesion-related MACE rate of 7·0% (95% CI 4·0–10·0). Patients in whom one or more such lesions were identified had a 4-year non-culprit lesion-related MACE rate of 13·2% (95% CI 9·4–17·6).InterpretationCombined NIRS and intravascular ultrasound detects angiographically non-obstructive lesions with a high lipid content and large plaque burden that are at increased risk for future adverse cardiac outcomes.FundingAbbott Vascular, Infraredx, and The Medicines Company.

Background The VALIDATE-SWEDEHEART trial was a registry-based randomized trial comparing bivalirudin and heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention. It showed no differences in mortality at 30 or 180 days. This study examines how well the trial population results may generalize to all of the screened patients with fulfilled inclusion criteria for mortality at 30 and 180 days.Methods The standardized difference in the mean propensity score for trial inclusion between the trial population and the screened not-enrolled with fulfilled inclusion criteria population was calculated as a metric of similarity. A predefined criterion of ≤ 0.25 was used. Predictions were futher used to standardize the observed trial results to all the screened patients with fulfilled inclusion criteria through an inverse-probability weighted Cox regression analysis, thereby evaluating the generalizability of the trial results to this population. An adjusted Cox regression analysis was applied to analyze differences in mortality with respect to anticoagulant treatment between the trial population and the screened not enrolled with fulfilled inclusion criteria.Results The propensity-score difference was 0.61, above the limit defining similar populations. There were no significant differences in mortality between bivalirudin and heparin in the inverse-probability weighted analysis [HR 1.11, 95% CI (0.73 1.68)]. In the interaction analysis, the neutral effect of bivalirudin vs. heparin remained in the screened not-enrolled with fulfilled inclusion criteria population [HR 1.01, 95% CI (0.63 1.61)].Conclusion The propensity-score difference demonstrated that the screened not enrolled with fulfilled inclusion criteria and the trial population were not similar. The inverse-probability weighted analysis showed no significant differences in mortality associated with treatment in either of the populations as was reiterated by the Cox analysis. From these analyses, we conclude that the VALIDATE trial results may be generalized.

Background We aimed to study the effect of social containment mandates on ACS presentation during COVID-19 pandemic using location activity and mobility data from mobile phone map services. Methods We conducted a cross-sectional study using data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) including all ACS presentations during the pandemic until 7 May 2020. Using a count regression model, we adjusted for day of the week, daily weather and incidence of COVID-19. Results A 10% increase in activity around areas of residence was associated with 38% lower rates of ACS hospitalizations, whereas increased activity relating to retail and recreation, grocery stores and pharmacies, workplaces and mode of mobility was associated with 10-20% higher rates of ACS hospitalizations. Conclusion Government policy regarding social containment mandates has important public health implications for medical emergencies such as ACS and may explain the decline in ACS presentations observed during COVID-19 pandemic. Funding Agencies|Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation Funding Source: Medline; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation Funding Source: Medline; Swedish Scientific Research CouncilSwedish Research Council Funding Source: Medline; ALF Funding Source: Medline; SSF (TOTAL-AMI) Funding Source: Medline; Bundy Academy Funding Source: Medline; Skane University Hospital Funds Funding Source: Medline; Marta Funding Source: Medline

Background Chloroquine was promoted as a COVID-19 therapeutic early in the pandemic. Most countries have since discontinued the use of chloroquine due to lack of evidence of any benefit and the risk of severe adverse events. The primary aim of this study was to examine if administering chloroquine during COVID-19 imposed an increased risk of ischemic heart injury or heart failure. Methods Medical records, laboratory findings, and electrocardiograms of patients with COVID-19 who were treated with 500 mg chloroquine phosphate daily and controls not treated with chloroquine were reviewed retrospectively. Controls were matched in age and severity of disease. Results We included 20 patients receiving chloroquine (500 mg twice daily) for an average of five days, and 40 controls. The groups were comparable regarding demographics and biochemical analyses including C-reactive protein, thrombocytes, and creatinine. There were no statistically significant differences in cardiac biomarkers or in electrocardiograms. Median troponin T was 10,8 ng/L in the study group and 17.9 ng/L in the control group, whereas median NT-proBNP was 399 ng/L in patients receiving chloroquine and 349 ng/L in the controls. Conclusions We found no increased risk of ischemic heart injury or heart failure as a result of administering chloroquine. However, the use of chloroquine to treat COVID-19 outside of clinical trials is not recommended, considering the lack of evidence of its effectiveness, as well as the elevated risk of fatal arrythmias.

While the first part of the scientific statement on the pathophysiology of Takotsubo syndrome was focused on catecholamines and the sympathetic nervous system, in the second part we focus on the vascular pathophysiology including coronary and systemic vascular responses, the role of the central and peripheral nervous systems during the acute phase and abnormalities in the subacute phase, the gender differences and integrated effects of sex hormones, genetics of Takotsubo syndrome including insights from microRNA studies and inducible pluripotent stem cell models of Takotsubo syndrome. We then discuss the chronic abnormalities of cardiovascular physiology in survivors, the limitations of current clinical and preclinical studies, the implications of the knowledge of pathophysiology for clinical management and future perspectives and directions of research. ispartof: EUROPEAN JOURNAL OF HEART FAILURE vol:24 issue:2 pages:274-286 ispartof: location:England status: published

ObjectiveThe comparative efficacy and safety of prasugrel and ticagrelor in patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI) remain unclear. We aimed to investigate the association of treatment with clinical outcomes.MethodsIn the SWEDEHEART (Swedish Web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies) registry, all patients with MI treated with PCI and discharged on prasugrel or ticagrelor from 2010 to 2016 were included. Outcomes were 1-year major adverse cardiac and cerebrovascular events (MACCE, death, MI or stroke), individual components and bleeding. Multivariable adjustment, inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were used to adjust for confounders.ResultsWe included 37 990 patients, 2073 in the prasugrel group and 35 917 in the ticagrelor group. Patients in the prasugrel group were younger, more often admitted with ST elevation MI and more likely to have diabetes. Six to twelve months after discharge, 20% of patients in each group discontinued the P2Y12 receptor inhibitor they received at discharge. The risk for MACCE did not significantly differ between prasugrel-treated and ticagrelor-treated patients (adjusted HR 1.03, 95% CI 0.86 to 1.24). We found no significant difference in the adjusted risk for death, recurrent MI or stroke alone between the two treatments. There was no significant difference in the risk for bleeding with prasugrel versus ticagrelor (2.5% vs 3.2%, adjusted HR 0.92, 95% CI 0.69 to 1.22). IPTW and PSM analyses confirmed the results.ConclusionIn patients with MI treated with PCI, prasugrel and ticagrelor were associated with similar efficacy and safety during 1-year follow-up.

Background Takotsubo syndrome (TS) is a potentially life‐threatening acute cardiac syndrome with a clinical presentation similar to myocardial infarction and for which the natural history, management, and outcome remain incompletely understood. Our aim was to assess the relative short‐term mortality risk of TS, ST‐segment–elevation myocardial infarction (STEMI), and non‐STEMI (NSTEMI) and to identify predictors of in‐hospital complications and poor prognosis in patients with TS. Methods and Results This is an observational cohort study based on the data from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry). We included all patients (n=117 720) who underwent coronary angiography in Sweden attributed to TS (N=2898 [2.5%]), STEMI (N=48 493 [41.2%]), or NSTEMI (N=66 329 [56.3%]) between January 2009 and February 2018. We compared patients with TS to those with NSTEMI or STEMI. The primary end point was all‐cause mortality at 30 days. Secondary outcomes were acute heart failure (Killip Class ≥2) and cardiogenic shock (Killip Class 4) at the time of angiography. Patients with TS were more often women compared with patients with STEMI or NSTEMI. TS was associated with unadjusted and adjusted 30‐day mortality risks lower than STEMI (adjusted hazard ratio [adjHR], 0.60; 95% CI, 0.48–0.76; P P P =0.16) but a lower risk of cardiogenic shock (adjHR, 0.55; 95% CI, 0.34–0.89; P =0.02). The relative 30‐day mortality risk for TS versus STEMI and NSTEMI was higher for smokers than nonsmokers (adjusted P interaction STEMI=0.01 and P interaction NSTEMI=0.01). Conclusions The 30‐day mortality rate in TS was higher than in NSTEMI but lower than STEMI despite a similar risk of acute heart failure in TS and STEMI. Among patients with TS, smoking was an independent predictor of mortality.

Background Characteristics and prognosis of patients admitted with strong suspicion of myocardial infarction (MI) but discharged without an MI diagnosis are not well-described. Objectives To compare background characteristics and cardiovascular outcomes in patients discharged with or without MI diagnosis. Methods The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial compared 6629 patients with strong suspicion of MI randomized to oxygen or ambient air. The main composite end-point of this subgroup analysis was the incidence of all-cause death, rehospitalization with MI, heart failure (HF) or stroke during a follow-up of 2.1 years (median; range: 1-3.7 years) irrespective of randomized treatment. Results 1619 (24%) received a non-MI discharge diagnosis, and 5010 patients (76%) were diagnosed with MI. Groups were similar in age, but non-MI patients were more commonly female and had more comorbidities. At thirty days, the incidence of the composite end-point was 2.8% (45 of 1619) in non-MI patients, compared to 5.0% (250 of 5010) in MI patients with lower incidences in all individual end-points. However, for the long-term follow-up, the incidence of the composite end-point increased in the non-MI patients to 17.7% (286 of 1619) as compared to 16.0% (804 of 5010) in MI patients, mainly driven by a higher incidence of all-cause death, stroke and HF. Conclusions Patients admitted with a strong suspicion of MI but discharged with another diagnosis had more favourable outcomes in the short-term perspective, but from one year onwards, cardiovascular outcomes and death deteriorated to a worse long-term prognosis. Funding Agencies|Swedish HeartLung FoundationSwedish Heart-Lung Foundation [HLF20160688, HLF20180187]; Stockholm County CouncilStockholm County Council [K 20174577]; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation [HLF20180287]

Background Intracoronary pressure wire measurements of fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) provide decision-making guidance during percutaneous coronary intervention (PCI). However, limited data exist on the impact of FFR/iFR on long-term clinical outcomes in patients with stable angina, unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI), or STEMI. Methods We used data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) on all patients in Sweden undergoing PCI (with or without FFR/iFR guidance) for stable angina, UA/NSTEMI, or STEMI between January 2005 and March 2018. The primary endpoint was all-cause mortality and the secondary endpoints were stent thrombosis or restenosis and periprocedural complications. The primary model was multilevel Cox proportional-hazards regression using an instrumental variable (IV) to adjust for known and unknown confounders with treating hospital as a treatment-preference instrument. The following variables were entered into Cox proportional-hazards regression in addition to the IV: age, sex, diabetes, indication for PCI, severity of coronary disease, smoking status, hypertension, hyperlipidemia, previous myocardial infarction, previous PCI, previous coronary artery bypass graft, type of stent. Results In total, 151,001 patients underwent PCI: 31,514 (20.9%) for stable angina, 74,982 (49.6%) for UA/NSTEMI, and 44,505 (29.5%) for STEMI. Of these, FFR/iFR guidance was used in 11,433 patients (7.6%): 5029 (44.0%) with stable angina, 5989 (52.4%) with UA/NSTEMI, and 415 (3.6%) with STEMI; iFR was used in 1156 (10.1%) of these patients. After a median follow-up of 1784 (range 1–4824) days, the FFR/iFR group had lower adjusted risk estimates for all-cause mortality [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.69–0.91; P=0.001] and stent thrombosis and restenosis (HR 0.13; 95% CI 0.09–0.19; P Conclusions In this observational study, the use of FFR/IFR was associated with a lower risk of long-term mortality in patients undergoing PCI for stable angina, UA/NSTEMI, or STEMI. Our study supports the current European and American guidelines for the use of FFR/iFR during PCI and shows that intracoronary pressure wire guidance has prognostic benefit in patients with stable angina as well as in patients with the acute coronary syndrome. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Heart and Lung Foundation, ALF Västra Götaland, Swedish Scientific Council

Background Several studies have compared CABG to PCI as revascularization treatment in patients with ischemic heart disease (IHD). However, it remains unclear which revascularization strategy carries survival benefits in the long-term. Methods We used data from the SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry for all hospital admissions at 13 cardiac care centers within Västra Götaland County in Sweden (∼20% of all SWEDEHEART data). The database contains >1000 clinical variables documenting the entire process of acute coronary hospital care. All patients hospitalized for stable angina or NSTE-ACS during the period 2000–2018 were included in the analysis. We used a propensity score-adjusted Cox proportional-hazards regression with hospitals as random-effect variables. We adjusted for patients' demographics, socio-economic status, traditional risk factors, comorbidities, the severity of coronary artery disease, left ventricular function, calendar year and medication at discharge. For sensitivity analysis, we used the instrumental variable estimator for the Cox proportional-hazards model (with treating hospital as a treatment-preference instrument) to simultaneously deal with the problems of unmeasured confounding and censoring of the outcome. The primary outcome was all-cause mortality. Results In total, 11,896 patients were included in the study. Of these, 3,129 (26.3%) were women. 20.4% had diabetes and 10.4% had a previous myocardial infarction. The mean age was 66.7±10.7, and 42.9% were >70 years old. 61.5% had three-vessel and/or left main disease. Median follow-up time was 5.7 years (range 1 day-18.2 years). Revascularization therapy after coronary angiography was PCI in 9449 (79.4%) and CABG in 2,447 (20.6%) patients. CABG patients were more likely to have diabetes, left main/multivessel disease and heart failure. The number of revascularized patients with PCI increased by 6.4% per calendar year (P0.05). Results from the sensitivity analysis support the conclusions from the primary model. Conclusions In hospitalized patients due to IHD, revascularization with CABG was associated with superior long-term survival compared to PCI. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Heart and Lung Foundation, ALF Västra Götaland, Swedish Scientific Council

Objectives This study sought to compare interrupted and uninterrupted oral anticoagulant therapy (I-OAC vs. U-OAC) in patients on OAC undergoing percutaneous coronary intervention. Background There is a paucity of data regarding the optimal peri-procedural management of OAC-treated patients. Methods In the SWEDEHEART registry, all patients on OAC who were admitted acutely and underwent percutaneous coronary intervention or coronary angiography with a diagnostic procedure, from 2005 to 2017, were included. Outcomes were major adverse cardiac and cerebrovascular events (MACCE; death, myocardial infarction, or stroke) and bleeds at 120 days. Propensity score was used to adjust for the nonrandomized treatment selection. Results The study included 6,485 patients: 3,322 in the I-OAC group and 3,163 in the U-OAC group. The cumulative incidence of MACCE was 8.2% (269 events) versus 8.2% (254 events) in the I-OAC and the U-OAC groups, respectively. The adjusted risk for MACCE did not differ between the groups (I-OAC vs. U-OAC hazard ratio: 0.89; 95% confidence interval: 0.71 to 1.12). Similarly, no difference was found in the risk for MACCE or bleeds (12.6% vs. 12.9%, adjusted hazard ratio: 0.87; 95% confidence interval: 0.70 to 1.07). The risk for major or minor in-hospital bleeds did not differ between the groups. However, U-OAC was associated with a significantly shorter duration of hospitalization: 4 (3 to 7) days versus 5 (3 to 8) days; p Conclusions I-OAC and U-OAC were associated with equivalent risk for MACCE and bleeding complications. An U-OAC strategy was associated with shorter length of hospitalization. These data support U-OAC as the preferable strategy in patients on OAC undergoing coronary intervention.

Background Ticagrelor reduces ischaemic end points in acute coronary syndromes. However, outcomes of ticagrelor versus clopidogrel in real‐world patients with acute coronary syndromes treated with percutaneous coronary intervention (PCI) remain unclear. We sought to examine whether treatment with ticagrelor is superior to clopidogrel in unselected patients with acute coronary syndromes treated with PCI. Methods and Results We used data from SCAAR (Swedish Coronary Angiography and Angioplasty Registry) for PCI performed in Västra Götaland County, Sweden. The database contains information about all PCI performed at 5 hospitals (∼20% of all data in SCAAR). All procedures between January 2005 and January 2015 for unstable angina/non‒ST‐segment‒elevation myocardial infarction and ST‐segment‒elevation myocardial infarction were included. We used instrumental variable 2‐stage least squares regression to adjust for confounders. The primary combined end point was mortality or stent thrombosis at 30 days, secondary end points were mortality at 30 days and 1‐year, stent thrombosis at 30 days, in‐hospital bleeding, in‐hospital neurologic complications and long‐term mortality. A total of 15 097 patients were included in the study of which 2929 (19.4%) were treated with ticagrelor. Treatment with ticagrelor was not associated with a lower risk for the primary end point (adjusted odds ratio [aOR], 1.20; 95% CI, 0.87–1.61; P =0.250). Estimated risk of death at 30 days (aOR, 1.18; 95% CI, 0.88–1.64; P =0.287) and at 1‐year (aOR, 1.28; 95% CI, 0.86–1.64; P =0.556) was not different between the groups. The risk of in‐hospital bleeding was higher with ticagrelor (aOR, 2.88; 95% CI, 1.53–5.44; P =0.001). Conclusions In this observational study, treatment with ticagrelor was not superior to clopidogrel in patients with acute coronary syndromes treated with PCI.

AIMS The Compare-Acute trial showed superiority of fractional flow reserve (FFR)-guided acute complete revascularisation compared to culprit-only treatment in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) at one year. The aim of this study was to investigate the outcome at three years, together with cost analysis of this strategy. METHODS AND RESULTS After primary percutaneous coronary intervention (PCI), 885 patients with STEMI and MVD were randomised (1:2 ratio) to FFR-guided complete revascularisation (295 patients) or infarct-related artery (IRA)-only treatment (590 patients). After 36 months, the primary endpoint (composite of death, myocardial infarction, revascularisation, stroke) occurred significantly less frequently in the FFR-guided complete revascularisation group: 46/295 patients (15.6%) versus 178/590 patients (30.2%) (HR 0.46, 95% CI: 0.33-0.64; p

Background: Elderly patients with acute myocardial infarction undergoing percutaneous coronary intervention are at increased risk of both ischemic and bleeding complications. The optimal anticoagulation strategy in these patients is uncertain. Therefore, we compared bivalirudin to heparin monotherapy in a contemporary cohort of such patients. Methods: A prespecified subgroup analysis of elderly patients with myocardial infarction (≥75 years) from the VALIDATE-SWEDEHEART trial (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) was performed. In the trial, patients were randomized to either bivalirudin or heparin monotherapy during percutaneous coronary intervention, with mandatory potent P2Y12 inhibition, routine radial artery access, and only bail-out glycoprotein IIb/IIIa inhibition. Kaplan-Meier event rates were assessed for the primary end point, consisting of a composite of all-cause death, myocardial reinfarction, or major bleeding, within 180 days. Results: The elderly (n=1592) had more than twice the risk of all events compared with younger patients (n=4406). Baseline and periprocedural characteristics were equal between bivalirudin (n=799) and heparin (n=793) treated patients ≥75 years. No differences were found in the elderly between bivalirudin and heparin monotherapy regarding the primary end point (180-day all-cause death, myocardial reinfarction, or major bleeding), the individual components of the primary end point, definite stent thrombosis, or stroke. Conclusions: In this prespecified subgroup analysis of the VALIDATE-SWEDEHEART trial, elderly patients with myocardial infarction had a highly increased risk of all events. However, no difference in outcomes could be observed with an anticoagulation strategy with either bivalirudin or heparin as monotherapy in this patient group.

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.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.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.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).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).

Background: Intracoronary pressure wire measurement of fractional flow reserve (FFR) provides decision-making guidance during percutaneous coronary intervention (PCI). However, limited data exist on the effect of FFR on long-term clinical outcomes in patients with stable angina pectoris. Objectives: The purpose of this study was to determine the association between the usage of FFR and all-cause mortality in patients with stable angina undergoing PCI. Methods: Data was used from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) on all patients undergoing PCI (with or without FFR guidance) for stable angina pectoris in Sweden between January 2005 and March 2016. The primary endpoint was all-cause mortality, and the secondary endpoints were stent thrombosis (ST) or restenosis and peri-procedural complications. The primary model was multilevel Cox proportional hazards regression adjusted with Kernel-based propensity score matching. Results: In total, 23,860 patients underwent PCI for stable angina pectoris; of these, FFR guidance was used in 3,367. After a median follow-up of 4.7 years (range 0 to 11.2 years), the FFR group had lower adjusted risk estimates for all-cause mortality (hazard ratio: 0.81; 95% confidence interval [CI]: 0.73 to 0.89; p < 0.001), and ST and restenosis (hazard ratio: 0.74; 95% CI: 0.57 to 0.96; p = 0.022). The number of peri-procedural complications did not differ between the groups (adjusted odds ratio: 0.96; 95% CI: 0.77 to 1.19; p = 0.697). Conclusions: In this observational study, the use of FFR was associated with a lower risk of long-term mortality, ST, and restenosis in patients undergoing PCI for stable angina pectoris. This study supports the current European and American guidelines for the use of FFR during PCI and shows that intracoronary pressure wire guidance confers prognostic benefit in patients with stable angina pectoris.

Background Type 2 diabetes is a major health problem in the world, and is strongly associated with impaired cardiac function and increased mortality. The causal relationship between type 2 diabetes and impaired cardiac function is still incompletely understood but changes in the cardiac lipid metabolism are believed to be a contributing factor. The objective of this study was to determine the lipid profile in human myocardial biopsies collected in vivo from patients with type 2 diabetes and compare to non-diabetic controls. Method We conducted full lipidomics analyses, using mass spectrometry, of 85 right atrial biopsies obtained from diabetic and non-diabetic patients undergoing elective cardiac surgery. The patients were characterized clinically and serum was analyzed for lipids and biochemical markers. Results The groups did not differ in BMI and in circulating triglycerides. We demonstrate that type 2 diabetes is associated with alterations in the cardiac lipidome. Interestingly, the absolute amount of lipids is not altered in the diabetic myocardium. However, triglycerides with longer fatty acyl chains are more abundant and there is a higher degree of unsaturated fatty acid chains in triglycerides in diabetic myocardium. Conclusions Our study reveals that type 2 diabetes is a relatively strong determinant of the human cardiac lipidome (compared to other clinical variables). Although the total lipid content in the diabetic myocardium is not increased, the lipid composition is markedly affected.

Objective Most reports on the declining incidence of myocardial infarction (MI) during the COVID-19 have either been anecdotal, survey results or geographically limited to areas with lockdowns. We examined the incidence of MI during the COVID-19 pandemic in Sweden, which has remained an open society with a different public health approach fighting COVID-19. Methods We assessed the incidence rate (IR) as well as the incidence rate ratios (IRRs) of all MI referred for coronary angiography in Sweden using the nationwide Swedish Coronary Angiography and Angioplasty Registry (SCAAR), during the COVID-19 pandemic in Sweden (1 March 2020-7 May 2020) in relation to the same days 2015-2019. Results A total of 2443 MIs were referred for coronary angiography during the COVID-19 pandemic resulting in an IR 36 MIs/day (204 MIs/100 000 per year) compared with 15 213 MIs during the reference period with an IR of 45 MIs/day (254 MIs/100 000 per year) resulting in IRR of 0.80, 95% CI (0.74 to 0.86), pFunding Agencies|Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation; Swedish Scientific Research CouncilSwedish Research Council; Swedish foundation for strategic research SSF (TOTAL-AMI); Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation; Avtal om lakarutbildning och forskning ALF; Bundy Academy; Skane University Hospital funds

Background: The optimal anti-coagulation strategy for patients with non-ST-elevation myocardial infarction treated with percutaneous coronary intervention is unclear in contemporary clinical practice of radial access and potent P2Y12-inhibitors. The aim of this study was to investigate whether bivalirudin was superior to heparin monotherapy in patients with non-ST-elevation myocardial infarction without routine glycoprotein IIb/IIIa inhibitor use. Methods: In a large pre-specified subgroup of the multicentre, prospective, randomised, registry-based, open-label clinical VALIDATE-SWEDEHEART trial we randomised patients with non-ST-elevation myocardial infarction undergoing percutaneous coronary intervention, treated with ticagrelor or prasugrel, to bivalirudin or heparin monotherapy with no planned use of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention. The primary endpoint was the rate of a composite of all-cause death, myocardial infarction or major bleeding within 180 days. Results: A total of 3001 patients with non-ST-elevation myocardial infarction, were enrolled. The primary endpoint occurred in 12.1% (182 of 1503) and 12.5% (187 of 1498) of patients in the bivalirudin and heparin groups, respectively (hazard ratio of bivalirudin compared to heparin treatment 0.96, 95% confidence interval 0.78–1.18, p=0.69). The results were consistent in all major subgroups. All-cause death occurred in 2.0% versus 1.7% (hazard ratio 1.15, 0.68–1.94, p=0.61), myocardial infarction in 2.3% versus 2.5% (hazard ratio 0.91, 0.58–1.45, p=0.70), major bleeding in 8.9% versus 9.1% (hazard ratio 0.97, 0.77–1.24, p=0.82) and definite stent thrombosis in 0.3% versus 0.2% (hazard ratio 1.33, 0.30–5.93, p=0.82). Conclusion: Bivalirudin as compared to heparin during percutaneous coronary intervention for non-ST-elevation myocardial infarction did not reduce the composite of all-cause death, myocardial infarction or major bleeding in non-ST-elevation myocardial infarction patients receiving current recommended treatments with modern P2Y12-inhibitors and predominantly radial access.

The dual antiplatelet therapy (DAPT) score guides decisions on DAPT duration after coronary stenting by simultaneously predicting ischemic and bleeding risk.This study sought to assess the performance of the DAPT score in a nationwide real-world population.The study used register data in Sweden (2006 to 2014) and followed 41,101 patients who had undergone 12 months of event-free DAPT, from months 12 to 30 after stenting. Risk of myocardial infarction (MI) or stent thrombosis, major adverse cardiovascular and cerebrovascular events (MACCE) (MI, stroke, and all-cause death), and fatal or major bleeding were compared according to DAPT score.The score had a discrimination of 0.58 (95% confidence interval [CI]: 0.56 to 0.60) for MI or stent thrombosis, 0.54 (95% CI: 0.53 to 0.55) for MACCE, and 0.49 (95% CI: 0.45 to 0.53) for fatal or major bleeding. Risk of MI or stent thrombosis was significantly increased at scores of ≥3 while MACCE risk followed a J-shaped pattern and increased at scores of ≥4. Absolute differences in fatal or major bleeding risk were small between scores. Event rates of ischemic and bleeding outcomes in patients with high (≥2) and low (2) scores differed compared to the DAPT Study from which the score was derived; fatal or major bleeding rates were approximately one-half of those in the placebo arm of the DAPT Study.In a nationwide population, the DAPT score did not adequately discriminate ischemic and bleeding risk, the relationship between score and ischemic risk did not correspond to the suggested decision rule for extended DAPT, and risk of bleeding was lower compared with the DAPT Study. The score and its decision rule may not be generalizable to real-world populations.

Aims Takotsubo syndrome (TS) is an acute cardiac syndrome characterized by regional myocardial akinesia that cannot be attributed to a culprit lesion in coronary arteries. Cardiac overstimulation by catecholamines in the setting of stress is implicated in the pathogenesis of TS. While catecholamine‐induced alterations in cardiac contractility have been studied as part of the causal pathway in TS, the importance of catecholamine‐mediated tachycardia has not been studied. Our aim was to explore whether the reduction in heart rate, either by pharmacological suppression of the sinoatrial node with ivabradine or by surgical induction of third‐degree atrioventricular block, prevents isoprenaline‐induced TS‐like akinesia in an experimental animal model. Methods and results We used 142 female Sprague–Dawley rats in two separate protocols. The TS‐like phenotype was induced by an intraperitoneal bolus dose of isoprenaline (ISO) 50 mg/kg. In the first protocol, we randomized 54 rats to ivabradine 10 min before ISO (IVAB1), ivabradine 10 min after ISO (IVAB2), or saline 10 min before ISO (CONTROL). In the second protocol, we randomized 88 rats to surgically induced complete heart block (CHB) or sham operation (CTRL) 10 min before the administration of ISO. All drugs were administered intraperitoneally. We recorded heart rate and blood pressure invasively in the right carotid artery. Cardiac morphology and function were evaluated by high‐resolution echocardiography (VisualSonics 770 VEVO, Toronto, Ontario, Canada) 90 min after ISO injection. IVAB1 and IVAB2 rats had significantly lower heart rate and less pronounced TS‐like cardiac dysfunction than CONTROL. CHB rats had a lower (54%) heart rate, and no animal developed left ventricular akinesia. In the first protocol, the CONTROL group had a median degree of akinesia of 10.2 [inter‐quartile range (IQR) 0.0–18.6]. The IVAB1 group showed a median of akinesia of 0% (IQR 0.0–0.0, P

Takotsubo syndrome was featured in various sessions and posters at the recent Heart Failure Congress and World Congress on Acute Heart Failure 2019 held in Athens. The importance and increasing recognition of this acute heart failure syndrome is reflected by the growing activity at Heart Failure Association congresses over the last 8 years. Two dedicated sessions to Takotsubo syndrome with comprehensive lectures from experts in the field and several posters highlighted new scientific progress, important aspects of epidemiology, pathophysiology, risk stratification, and management of the syndrome and discussed gaps in knowledge of this intriguing entity. This paper will summarize the topics discussed in these sessions including the most recent data from large registries, clinical, and pre‐clinical studies presented at the meeting.

Objectives In this substudy of the DETO2X-AMI (An Efficacy and Outcome Study of Supplemental Oxygen Treatment in Patients With Suspected Myocardial Infarction) trial, the authors aimed to assess the analgesic effect of moderate-flow oxygen supplementation in patients with suspected acute myocardial infarction (AMI) treated with percutaneous coronary intervention (PCI) and to study the effect of oxygen supplementation on the use of opiates and sedatives during PCI. Background Routine oxygen in normoxemic patients with AMI does not provide clinical benefit. However, oxygen may relieve ischemic pain. Methods Patients were randomly allocated to oxygen or ambient air according to the main study protocol. After PCI, peak level of pain during PCI was measured by the Visual Analogue Scale. The total amount of opiates and sedatives was reported. Results A total of 622 patients were enrolled: 330 in the oxygen group and 292 in the ambient air group. There was no significant difference in peak level of pain (oxygen 4.0 [1.0 to 6.0] vs. air 3.0 [0.6 to 6.0]; p = 0.37), use of opiates (mg) (oxygen 0.0 [0.0 to 3.0] vs. air 0.0 [0.0 to 3.0]; p = 0.31), or use of sedatives between the groups (median [interquartile range]) (oxygen 2.5 [0.0 to 2.5] vs. air 2.5 [0.0 to 2.5]; p = 0.74). Conclusions In the present study, the authors did not find any analgesic effect of routine oxygen as compared with ambient air, and no differences in the use of sedatives and opiates during PCI. Our results indicate that moderate-flow oxygen supplementation does not relieve pain in normoxemic patients with suspected AMI undergoing treatment with PCI and should thus not be used for this purpose.

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.

Takotsubo syndrome (TTS) is a poorly recognized heart disease that was initially regarded as a benign condition. Recently, it has been shown that TTS may be associated with severe clinical complications including death and that its prevalence is probably underestimated. Since current guidelines on TTS are lacking, it appears timely and important to provide an expert consensus statement on TTS. The clinical expert consensus document part I summarizes the current state of knowledge on clinical presentation and characteristics of TTS and agrees on controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease, and etiology. This consensus also proposes new diagnostic criteria based on current knowledge to improve diagnostic accuracy. ispartof: EUROPEAN HEART JOURNAL vol:39 issue:22 pages:2032-2046 ispartof: location:England status: published

Aims: Long-term comparisons between Drug-eluting stent and bare metal stent are not well-studied. The aim of this study was to compare two stents that were previously frequently used in regard to long-term risk of restenosis and stent thrombosis (ST). Methods and results: We used data from the SCAAR registry. Consecutive procedures performed between 2004 and 2014 for stable angina, UA/NSTEMI and STEMI were included. We compared two different stents: Cordis Cypher Select (C-CS), and Boston Scientific Liberte (BS-L), modeling data with multilevel Cox proportional-hazards regression. The primary endpoint was time to first occurrence of either ST or restenosis. During the study period 2210 C-CS and 6941 B-SL were implanted in 5,314 patients. Mean follow-up time was 2,288 days for C-CS and 2,297 days for BS-L. Treatment with C-CS was associated with lower risk for restenosis or ST up to one year from index procedure (HR 0.41; 95% CI 0.32-0.52; P

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

Introduction Takotsubo syndrome (TS) is an acute cardiac condition that is often triggered by critical illness but that has rarely been studied in the intensive care unit (ICU) setting. The aim of this study was to (i) estimate the incidence of TS in a hemodynamically unstable ICU-population; (ii) identify predictors of TS in this population; (iii) study the impact of TS on prognosis and course of hospitalization. Methods Medical records from all patients admitted to our general ICU from 2012 to 2015 were analyzed. TS was defined as having transient regional wall motion abnormalities (RWMA) with a typical pattern not attributable to a history of coronary artery disease or acute coronary syndromes. Results Out of 6470 patients admitted to the ICU, echocardiography due to hemodynamic instability was performed in 1051 patients; 467 had LV dysfunction and 59 fulfilled TS criteria. Patients with TS had higher SAPS 3 scores on admission than patients with normal LV function. Septic shock, cardiac arrest, cerebral mass lesion, female sex and low pH were independently associated with TS on admission. Patients with TS needed more ICU resources measured by higher NEMS scores and longer ICU-stay. Crude mortality was higher in TS patients (32%) vs the ICU-population (20%, P = 0.020), but there were no differences in a SAPS 3 adjusted analysis. Conclusion TS was not an uncommon cause of LV dysfunction in hemodynamically unstable ICU-patients. Furthermore, TS was associated with a more complex disease. TS is a complication to take in consideration in the critically ill.

Background It remains unclear whether radial access (RA), compared with femoral access (FA), mitigates the risk of acute kidney injury (AKI). Objectives The authors assessed the incidence of AKI in patients with acute coronary syndrome (ACS) enrolled in the MATRIX-Access (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial. Methods Among 8,404 patients, 194 (2.3%) were excluded due to missing creatinine values, no or an incomplete coronary angiogram, or previous dialysis. The primary AKI-MATRIX endpoint was AKI, defined as an absolute (>0.5 mg/dl) or a relative (>25%) increase in serum creatinine (sCr). Results AKI occurred in 634 patients (15.4%) with RA and 712 patients (17.4%) with FA (odds ratio [OR]: 0.87; 95% confidence interval [CI]: 0.77 to 0.98; p = 0.0181). A >25% sCr increase was noted in 633 patients (15.4%) with RA and 710 patients (17.3%) with FA (OR: 0.87; 95% CI: 0.77 to 0.98; p = 0.0195), whereas a >0.5 mg/dl absolute sCr increase occurred in 175 patients (4.3%) with RA versus 223 patients (5.4%) with FA (OR: 0.77; 95% CI: 0.63 to 0.95; p = 0.0131). By implementing the Kidney Disease Improving Global Outcomes criteria, AKI was 3-fold less prevalent and trended lower with RA (OR: 0.85; 95% CI: 0.70 to 1.03; p = 0.090), with stage 3 AKI occurring in 28 patients (0.68%) with RA versus 46 patients (1.12%) with FA (p = 0.0367). Post-intervention dialysis was needed in 6 patients (0.15%) with RA and 14 patients (0.34%) with FA (p = 0.0814). Stratified analyses suggested greater benefit with RA than FA in patients at greater risk for AKI. Conclusions In ACS patients who underwent invasive management, RA was associated with a reduced risk of AKI compared with FA. (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX [MATRIX]; NCT01433627 )

Aims What the best strategy is for nonculprit lesions in ST-elevation myocardial infarction (STEMI) patients presenting with multivessel disease remains a clinical dilemma. Based on recent clinical studies suggesting that complete revascularization in the acute phase is beneficial, the European Society of Cardiology and American College of Cardiology/American Heart Association guidelines have been recently changed from class 3 discouragement to a class 2B recommendation concerning the treatment of the nonculprit lesions in the acute index procedure. However, in these recent studies, nonculprit lesion treatment was guided by angiography, which is known for its poor accuracy in determining ischemia. Fractional flow reserve (FFR) guidance for treatment of nonculprit vessels seems to be a reasonable approach, and in the acute setting of STEMI, it is not yet investigated. The COMPARE-ACUTE trial aims to investigate FFR-guided complete revascularization in comparison to a culprit lesion treatment–only strategy in STEMI patients with multivessel disease presenting for primary percutaneous coronary intervention. Methods and results COMPARE-ACUTE is an investigator-initiated, prospective multicenter randomized controlled trial. After successful primary percutaneous coronary intervention, patients will be randomized in a 1:2 fashion toward FFR-guided complete revascularization or culprit lesion treatment–only strategies. The chosen primary end point is a composite of all-cause mortality, nonfatal myocardial infarction, any revascularization, and cerebrovascular events (major adverse cardiac and cerebrovascular events) at 12 months, with 3-year follow-up. Based on estimated event rates, a sample size of 885 patients is needed to show superiority of the FFR-guided revascularization with 80% power. Conclusion The aim of the COMPARE-ACUTE trial is to assess whether FFR-guided complete revascularization in the acute setting is superior to culprit lesion treatment–only therapy.

In patients with ST-segment elevation myocardial infarction (STEMI), the use of percutaneous coronary intervention (PCI) to restore blood flow in an infarct-related coronary artery improves outcomes. The use of PCI in non-infarct-related coronary arteries remains controversial.We randomly assigned 885 patients with STEMI and multivessel disease who had undergone primary PCI of an infarct-related coronary artery in a 1:2 ratio to undergo complete revascularization of non-infarct-related coronary arteries guided by fractional flow reserve (FFR) (295 patients) or to undergo no revascularization of non-infarct-related coronary arteries (590 patients). The FFR procedure was performed in both groups, but in the latter group, both the patients and their cardiologist were unaware of the findings on FFR. The primary end point was a composite of death from any cause, nonfatal myocardial infarction, revascularization, and cerebrovascular events at 12 months. Clinically indicated elective revascularizations performed within 45 days after primary PCI were not counted as events in the group receiving PCI for an infarct-related coronary artery only.The primary outcome occurred in 23 patients in the complete-revascularization group and in 121 patients in the infarct-artery-only group that did not receive complete revascularization, a finding that translates to 8 and 21 events per 100 patients, respectively (hazard ratio, 0.35; 95% confidence interval [CI], 0.22 to 0.55; P0.001). Death occurred in 4 patients in the complete-revascularization group and in 10 patients in the infarct-artery-only group (1.4% vs. 1.7%) (hazard ratio, 0.80; 95% CI, 0.25 to 2.56), myocardial infarction in 7 and 28 patients, respectively (2.4% vs. 4.7%) (hazard ratio, 0.50; 95% CI, 0.22 to 1.13), revascularization in 18 and 103 patients (6.1% vs. 17.5%) (hazard ratio, 0.32; 95% CI, 0.20 to 0.54), and cerebrovascular events in 0 and 4 patients (0 vs. 0.7%). An FFR-related serious adverse event occurred in 2 patients (both in the group receiving infarct-related treatment only).In patients with STEMI and multivessel disease who underwent primary PCI of an infarct-related artery, the addition of FFR-guided complete revascularization of non-infarct-related arteries in the acute setting resulted in a risk of a composite cardiovascular outcome that was lower than the risk among those who were treated for the infarct-related artery only. This finding was mainly supported by a reduction in subsequent revascularizations. (Funded by Maasstad Cardiovascular Research and others; Compare-Acute ClinicalTrials.gov number, NCT01399736 .).

The prognostic role of hypertension on long-term survival after percutaneous coronary intervention (PCI) is limited and inconsistent. We hypothesize that hypertension increases long-term mortality after PCI.We analyzed data from SCAAR (Swedish Coronary Angiography and Angioplasty Registry) for all consecutive patients admitted coronary care units in Sweden between January 1995 and May 2013 and who underwent PCI due to ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI)/unstable angina (UA) or stable angina pectoris. We used Cox proportional-hazards regression for statistical modelling on complete-case data as well as on imputed data sets. We used interaction test to evaluate possible effect-modulation of hypertension on risk estimates in several pre-specified subgroups: age categories, gender, diabetes, smoking and indication for PCI (STEMI, NSTEMI/UA and stable angina).During the study period, 175,892 consecutive patients underwent coronary angiography due to STEMI, NSTEMI/UA or stable angina. 78,100 (44%) of these had hypertension. Median follow-up was 5.5 years. After adjustment for differences in patient's characteristics, hypertension was associated with increased risk for mortality (HR 1.12, 95% CI 1.09-1.15, p .001). In subgroup analysis, risk was highest in patients less than 65 years, in smokers and in patients with STEMI. The risk was lowest in patients with stable angina (p .001 for interaction test).Hypertension is associated with higher mortality in patients with STEMI, NSTEMI/UA or stable angina who are treated with PCI.

Background Compare-Acute trial showed a 1-year superior outcome of FFR-guided acute complete revascularization (FFR-CR) compared to culprit-lesion-only revascularization (CLO) in patients presenting with ST-segment elevation myocardial infarction (STEMI) and multi-vessel disease (MVD). Long-term results and financial impact of this strategy are unknown. Purpose To evaluate if FFR-CR strategy is superior to CLO strategy in terms of health care costs at 3 year follow-up. Methods Compare-Acute is a multicenter, investigator-initiated prospective randomized controlled trial that involved 24 sites. Patients with STEMI and MVD were randomized 1:2 after successful primary PCI, towards FFR-CR or CLO treatment strategies (295 vs 590 pts). All stenosis ≥50% by angiography in the non-infarct artery were investigated by FFR in both arms. In the FFR-CR arm, all non-culprit (NC) lesions with a FFR ≤0.80 were treated by PCI. In the CLO arm pts underwent blinded FFR procedure of the NC lesions. Further treatment of these lesions was based on symptoms and/or ischemia testing during follow-up with an allowed treatment window of 45 days. The primary endpoint was defined as a composite of all-cause mortality, non-fatal myocardial infarction, any revascularization and cerebrovascular events (MACCE) at 12 months. The major secondary endpoints are MACCE and health care costs from both strategies up to 3-year follow-up. Cost-analysis is done from an insurance/governmental perspective in countries that use Diagnosis Related Group (DRG) costs: the Netherlands, Germany, Sweden and Poland. Results 1-year results have already been published and showed superior outcome of patients in the FFR-CR arm. According to the Dutch system, at 1 year of follow-up the average cost per patient was 8.150€ in the FFR-CR arm, and 10.319€ in the CLO arm (−21%). The better cost-effectiveness of FFR-CR strategy remained at 3 years of follow-up: average cost per patient was 8.653€ in the FFR-CR arm and 11.100€ in the CLO arm (−22%). Same 3-year data was confirmed using DRG analysis according to the German system (FFR-CR 4.887€ vs CLO 5.200€; −6.0%) and the Swedish system (FFR-CR 6.205€ vs CLO 8.133€; −23.7%). FFR-CR strategy was not more costly according to the Polish system (FFR-CR 3.704€ vs CLO 3.685€; +0.5%). Moreover, the better outcome of the FFR-CR group was mantained at 3 year follow-up (data not shown). Figure 1 Conclusion Our cost-analysis of the Compare Acute Trial shows that the strategy of FFR-guided complete revascularization in patients with STEMI and MVD is not only superior in terms of outcome, but also in terms of health care costs at 1 year. This benefit is maintained at 3 years follow-up.

Background Compare-Acute trial showed a 1-year superior outcome of FFR-guided acute complete revascularization (FFR-CR) compared to culprit-lesion-only revascularization (CLO) in patients presenting with ST-segment elevation myocardial infarction (STEMI) and multi-vessel disease (MVD). Long-term outcome results are unknown. Purpose To evaluate if FFR-CR strategy is superior to CLO strategy in terms of outcome at 3 year follow-up. Methods Compare-Acute is a multicenter, investigator-initiated prospective randomized controlled trial that involved 24 sites. Patients with STEMI and MVD were randomized, after successful primary PCI towards FFR-CR or CLO treatment strategies with a 1:2 ratio (295 pts vs 590 pts). All stenosis ≥50% in the non-infarct artery were investigated by FFR in both arms. In the FFR-CR arm, all non-culprit (NC) lesions with a FFR ≤0.80 were treated by PCI. In the CLO arm pts underwent blinded FFR procedure of the NC lesions. Further treatment of these lesions was based on symptoms and/or ischemia testing during follow-up with an allowed treatment window of 45 days. The primary endpoint was defined as a composite of all-cause mortality, non-fatal myocardial infarction, any revascularization and cerebrovascular events (MACCE) at 12 months. The major secondary endpoint is MACCE from both strategies up to 3-year follow-up. Results 1-year clinical outcomes have already been presented and published. At 36 months the composite end-point of MACCE occurred in 46 patients in the FFR-CR group vs 178 patients in the CLO group (15.6% vs 30.2%; HR 0.46, 95% CI 0.29–0.59; p MACCE-free survival at 3 years Conclusion With this analysis of the Compare-Acute trial we confirm that the benefit of a FFR-guided complete revascularization strategy in patients with STEMI and MVD is maintained at 3 years of follow-up. This difference is mainly driven by increased revascularizations in the CLO arm, but also by increased incidence of MI in the CLO subgroup with FFR+ lesions that were left untreated.

ObjectiveTo assess the risk of future death and cardiac events following percutaneous coronary intervention (PCI) in patients using smokeless tobacco, snus, compared with patients not using snus at admission for a first PCI.MethodsThe Swedish Coronary Angiography and Angioplasty Registry is a prospective registry on coronary diagnostic procedures and interventions. A total of 74 958 patients admitted for a first PCI were enrolled between 2009 and 2018, 6790 snus users and 68 168 not using snus. We used Cox proportional hazards regression for statistical modelling on imputed datasets as well as complete-case datasets.ResultsPatients using snus were younger (mean (SD) age 61.0 (±10.2) years) than patients not using snus (67.6 (±11.1), pConclusionsSnus use at admission for a first PCI was not associated with a higher occurrence of all-cause mortality, new revascularisation or heart failure hospitalisation. Discontinuing snus after a first PCI was associated with a significantly longer duration to a subsequent PCI.

Introduction International guidelines recommend performing percutaneous coronary intervention (PCI) on stable coronary lesions with a positive fractional flow reserve (FFR) to improve clinical outcomes. It remains unclear if FFR positive lesions with preserved coronary flow reserved (CFR) might be better treated medically. Purpose This study compared clinical outcomes between PCI and medical therapy for stable FFR-positive lesions with preserved CFR. Methods We performed a substudy of the randomized, multicenter COMPARE-ACUTE trial in which treated ST-elevation myocardial infarction patients with stable non-culprit lesions were randomized to either FFR-guided PCI or medical therapy. Based on baseline and hyperaemic pressure gradients, we computed the so-called pressure bounded-CFR (pb-CFR) and classified lesions as low ( Results A total of 980 lesions from 885 subjects were included in this sub-study due to availability of baseline and hyperaemic pressure gradients. For the 462 lesions with FFR≤0.80, 249 had a pb-CFR Conclusions In this post-hoc substudy from a large randomized controlled trial of 885 subjects with 980 lesions, a preserved pb-CFR≥2 did not associate with an improved clinical outcome when FFR≤0.80. Subjects with FFR-positive coronary lesions but a preserved pb-CFR experienced significantly worse clinical outcomes when treated medically instead of with PCI. These data suggest that a stenosis with a FFR≤0.80, even when pb-CFR remains preserved, benefits from treatment with PCI. Acknowledgement/Funding Maasstad Cardiovascular Research, Abbott Vascular and St. Jude Medical