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Background Stress-induced hyperglycaemia at time of hospital admission has been linked to worse prognosis following acute myocardial infarction (AMI). In addition to glucose, other glucose-related indices, such as HbA1c, glucose-HbA1c ratio (GHR), and stress-hyperglycaemia ratio (SHR) are potential predictors of clinical outcomes following AMI. However, the optimal blood glucose, HbA1c, GHR, and SHR cut-off values for predicting adverse outcomes post-AMI are unknown. As such, we determined the optimal blood glucose, HbA1c, GHR, and SHR cut-off values for predicting 1-year all cause mortality in diabetic and non-diabetic ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients. Methods We undertook a national, registry-based study of patients with AMI from January 2008 to December 2015. We determined the optimal blood glucose, HbA1c, GHR, and SHR cut-off values using the Youden’s formula for 1-year all-cause mortality. We subsequently analyzed the sensitivity, specificity, positive and negative predictive values of the cut-off values in the diabetic and non-diabetic subgroups, stratified by the type of AMI. Results There were 5841 STEMI and 4105 NSTEMI in the study. In STEMI patients, glucose, GHR, and SHR were independent predictors of 1-year all-cause mortality [glucose: OR 2.19 (95% CI 1.74–2.76); GHR: OR 2.28 (95% CI 1.80–2.89); SHR: OR 2.20 (95% CI 1.73–2.79)]. However, in NSTEMI patients, glucose and HbA1c were independently associated with 1-year all-cause mortality [glucose: OR 1.38 (95% CI 1.01–1.90); HbA1c: OR 2.11 (95% CI 1.15–3.88)]. In diabetic STEMI patients, SHR performed the best in terms of area-under-the-curve (AUC) analysis (glucose: AUC 63.3%, 95% CI 59.5–67.2; GHR 68.8% 95% CI 64.8–72.8; SHR: AUC 69.3%, 95% CI 65.4–73.2). However, in non-diabetic STEMI patients, glucose, GHR, and SHR performed equally well (glucose: AUC 72.0%, 95% CI 67.7–76.3; GHR 71.9% 95% CI 67.7–76.2; SHR: AUC 71.7%, 95% CI 67.4–76.0). In NSTEMI patients, glucose performed better than HbA1c for both diabetic and non-diabetic patients in AUC analysis (For diabetic, glucose: AUC 52.8%, 95% CI 48.1–57.6; HbA1c: AUC 42.5%, 95% CI 37.6–47. For non-diabetic, glucose: AUC 62.0%, 95% CI 54.1–70.0; HbA1c: AUC 51.1%, 95% CI 43.3–58.9). The optimal cut-off values for glucose, GHR, and SHR in STEMI patients were 15.0 mmol/L, 2.11, and 1.68 for diabetic and 10.6 mmol/L, 1.72, and 1.51 for non-diabetic patients respectively. For NSTEMI patients, the optimal glucose values were 10.7 mmol/L for diabetic and 8.1 mmol/L for non-diabetic patients. Conclusions SHR was the most consistent independent predictor of 1-year all-cause mortality in both diabetic and non-diabetic STEMI, whereas glucose was the best predictor in NSTEMI patients.

Aims The prognostic importance of cardiac procedural myocardial injury and myocardial infarction (MI) in chronic coronary syndrome (CCS) patients undergoing elective percutaneous coronary intervention (PCI) is still debated. Methods and results We analysed individual data of 9081 patients undergoing elective PCI with normal pre-PCI baseline cardiac troponin (cTn) levels. Multivariate models evaluated the association between post-PCI elevations in cTn and 1-year mortality, while an interval analysis evaluated the impact of the size of the myocardial injury on mortality. Our analysis was performed in the overall population and also according to the type of cTn used [52.0% had high-sensitivity cTn (hs-cTn)]. Procedural myocardial injury, as defined by the Fourth Universal Definition of MI (UDMI) [post-PCI cTn elevation ≥1 × 99th percentile upper reference limit (URL)], occurred in 52.8% of patients and was not associated with 1-year mortality [adj odds ratio (OR), 1.35, 95% confidence interval (CI) (0.84–1.77), P = 0.21]. The association between post-PCI cTn elevation and 1-year mortality was significant starting ≥3 × 99th percentile URL. Major myocardial injury defined by post-PCI ≥5 × 99th percentile URL occurred in 18.2% of patients and was associated with a two-fold increase in the adjusted odds of 1-year mortality [2.29, 95% CI (1.32–3.97), P = 0.004]. In the subset of patients for whom periprocedural evidence of ischaemia was collected (n = 2316), Type 4a MI defined by the Fourth UDMI occurred in 12.7% of patients and was strongly associated with 1-year mortality [adj OR 3.21, 95% CI (1.42–7.27), P = 0.005]. We also present our results according to the type of troponin used (hs-cTn or conventional troponin). Conclusion Our analysis has demonstrated that in CCS patients with normal baseline cTn levels, the post-PCI cTn elevation of ≥5 × 99th percentile URL used to define Type 4a MI is associated with 1-year mortality and could be used to detect ‘major’ procedural myocardial injury in the absence of procedural complications or evidence of new myocardial ischaemia.

Objective Novel hepatoprotective strategies are needed to improve clinical outcomes during liver surgery. There is mixed data on the role of remote ischemic preconditioning (RIPC). We investigated RIPC in partial hepatectomy for primary hepatocellular carcinoma (HCC). Methods This was a Phase II, single-center, sham-controlled, randomized controlled trial (RCT). The primary hypothesis was that RIPC would reduce acute liver injury following surgery indicated by serum alanine transferase (ALT) 24 h following hepatectomy in patients with primary HCC, compared to sham. Patients were randomized to receive either four cycles of 5 min/5 min arm cuff inflation/deflation immediately prior to surgery, or sham. Secondary endpoints included clinical, biochemical and pathological outcomes. Liver function measured by Indocyanine Green pulse densitometry was performed in a subset of patients. Results 24 and 26 patients were randomized to RIPC and control groups respectively. The groups were balanced for baseline characteristics, except the duration of operation was longer in the RIPC group. Median ALT at 24 h was similar between groups (196 IU/L IQR 113.5–419.5 versus 172.5 IU/L IQR 115–298 respectively, p = 0.61). Groups were similar in secondary endpoints. Conclusion This RCT did not demonstrate beneficial effects with RIPC on serum ALT levels 24 h after partial hepatectomy.

Circadian patterns in ST-segment elevation myocardial infarction (STEMI) patients have been previously reported, but little is known about the impact of time dependence of symptom onset on long-term prognosis. Our study population consisted of 11,731 STEMI patients treated by primary percutaneous coronary intervention (PPCI), enrolled in the Singapore Myocardial Infarction Registry (SMIR). Analysis of STEMI incidence trends over the 24-hour period showed the highest rate of symptom onset in the morning, with the peak incidence at 09:00 am . Patients with symptom onset in between 00:00 am -5:59 am showed the highest prevalence of diabetes (P = .010) and anterior STEMI (P pm -11:59 pm and 00:00 am -05:59 am having an estimated 30% to 50% higher risk of rehospitalization for HF at 1 year. Moreover, symptom onset remained a predictor of worse prognosis only in the subgroup of patients with symptoms lasting longer than 120 minutes. The results of this study demonstrate for the first time that rehospitalization for HF in STEMI patients treated with PPCI has a dependence on the time of onset of symptoms, with prolonged ischemia time playing a pivotal role. This may be an additional risk factor to identify those who warrant closer monitoring and more rigorous optimization of their treatment at follow-up, to improve their outcomes.

The effect of limb remote ischaemic conditioning (RIC) on myocardial infarct (MI) size and left ventricular ejection fraction (LVEF) was investigated in a pre-planned cardiovascular magnetic resonance (CMR) substudy of the CONDI-2/ERIC-PPCI trial. This single-blind multi-centre trial (7 sites in UK and Denmark) included 169 ST-segment elevation myocardial infarction (STEMI) patients who were already randomised to either control (n = 89) or limb RIC (n = 80) (4 × 5 min cycles of arm cuff inflations/deflations) prior to primary percutaneous coronary intervention. CMR was performed acutely and at 6 months. The primary endpoint was MI size on the 6 month CMR scan, expressed as median and interquartile range. In 110 patients with 6-month CMR data, limb RIC did not reduce MI size [RIC: 13.0 (5.1–17.1)% of LV mass; control: 11.1 (7.0–17.8)% of LV mass, P = 0.39], or LVEF, when compared to control. In 162 patients with acute CMR data, limb RIC had no effect on acute MI size, microvascular obstruction and LVEF when compared to control. In a subgroup of anterior STEMI patients, RIC was associated with lower incidence of microvascular obstruction and higher LVEF on the acute scan when compared with control, but this was not associated with an improvement in LVEF at 6 months. In summary, in this pre-planned CMR substudy of the CONDI-2/ERIC-PPCI trial, there was no evidence that limb RIC reduced MI size or improved LVEF at 6 months by CMR, findings which are consistent with the neutral effects of limb RIC on clinical outcomes reported in the main CONDI-2/ERIC-PPCI trial.

Background: The pathophysiology and trajectory of multiorgan involvement in post-COVID-19 syndrome is uncertain. Methods: A prospective, multicenter, longitudinal, cohort study involving post-COVID-19 patients enrolled in-hospital or early post-discharge (visit 1) and re-evaluated 28-60 days post-discharge (visit 2). Multisystem investigations included chest computed tomography with pulmonary and coronary angiography, cardiovascular and renal magnetic resonance imaging, digital electrocardiography, and multisystem biomarkers. The primary outcome was the adjudicated likelihood of myocarditis.Results: 161 patients (mean age 55 years, 43% female) and 27 controls with similar age, sex, ethnicity, and vascular risk factors were enrolled from 22 May 2020 to 2 July 2021 and had a primary outcome evaluation. Compared to controls, at 28-60 days post-discharge, patients with COVID-19 had persisting evidence of cardio-renal involvement, systemic inflammation, and hemostasis pathway activation. Myocarditis was adjudicated as being not likely (n=17; 10%), unlikely (n=56; 35%), probable (n=67; 42%) or very likely (n=21; 13%). Acute kidney injury (odds ratio, 95% confidence interval: 3.40 (1.13, 11.84); p=0.038) and low hemoglobin A1c (0.26 (0.07, 0.87); p=0.035) were multivariable associates of adjudicated myocarditis. During convalescence, compared to controls, COVID-19 was associated with worse health-related quality of life (EQ5D-5L) (pConclusions: The illness trajectory of COVID-19 includes persisting cardio-renal inflammation, lung damage and hemostasis activation. Adjudicated myocarditis occurred in one in eight hospitalized patients and was associated with impairments in health status, physical and psychological wellbeing during community convalescence. Public registration: ClinicalTrials.gov identifier is NCT04403607.

Background Stress-induced hyperglycaemia at time of hospital admission has been linked to worse prognosis following acute myocardial infarction (AMI). The stress-hyperglycaemia ratio (SHR) index normalises the acute increase in blood glucose values to background glycaemic status. However, the optimal cut-off blood glucose and SHR values for predicting adverse outcomes post-AMI are unknown. As such, we determined the optimal blood glucose and SHR cut-offs for predicting 1-year all cause mortality in diabetic and non-diabetic non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI) patients. Methods We undertook a national, registry-based study of patients with AMI from January 2008 to December 2015. We determined the optimal blood glucose and SHR cut-off values using the Youden’s formula for 1-year all-cause mortality. We subsequently analyzed the sensitivity, specificity, positive and negative predictive values of the cut-offs in the diabetic and non-diabetic subgroups, stratified by the type of AMI. Results There were 5,841 STEMI and 4,105 NSTEMI in the study. In STEMI patients, both glucose and SHR were independent predictors of 1-year all-cause mortality [Glucose: OR 2.19 (95% CI 1.74–2.75); SHR: 2.19 (95% CI 1.73–2.78)]. However, in NSTEMI patients, glucose and SHR were not independently associated with 1-year all-cause mortality [Glucose: OR 1.37 (95% CI 1.00-1.89); SHR: 1.27 (95% CI 0.91–1.78)]. In STEMI patients, ROC analysis showed that SHR performed better than glucose (AUC for glucose 0.633 versus AUC for SHR 0.692, P

A substantial number of chronic coronary syndrome (CCS) patients undergoing percutaneous coronary intervention (PCI) experience periprocedural myocardial injury or infarction. Accurate diagnosis of these PCI-related complications is required to guide further management given that their occurrence may be associated with increased risk of major adverse cardiac events (MACE). Due to lack of scientific data, the cut-off thresholds of post-PCI cardiac troponin (cTn) elevation used for defining periprocedural myocardial injury and infarction, have been selected based on expert consensus opinions, and their prognostic relevance remains unclear. In this Consensus Document from the ESC Working Group on Cellular Biology of the Heart and European Association of Percutaneous Cardiovascular Interventions (EAPCI), we recommend, whenever possible, the measurement of baseline (pre-PCI) cTn and post-PCI cTn values in all CCS patients undergoing PCI. We confirm the prognostic relevance of the post-PCI cTn elevation >5× 99th percentile URL threshold used to define type 4a myocardial infarction (MI). In the absence of periprocedural angiographic flow-limiting complications or electrocardiogram (ECG) and imaging evidence of new myocardial ischaemia, we propose the same post-PCI cTn cut-off threshold (>5× 99th percentile URL) be used to define prognostically relevant ‘major’ periprocedural myocardial injury. As both type 4a MI and major periprocedural myocardial injury are strong independent predictors of all-cause mortality at 1 year post-PCI, they may be used as quality metrics and surrogate endpoints for clinical trials. Further research is needed to evaluate treatment strategies for reducing the risk of major periprocedural myocardial injury, type 4a MI, and MACE in CCS patients undergoing PCI., Graphical Abstract An overview of the suggested approach to diagnosing the presence of ‘minor’ and prognostically relevant ‘major’ periprocedural myocardial injury (as defined in this Consensus document) and type 4a myocardial infarction (as defined by the 4th Universal Definition of Myocardial Infarction) in chronic coronary syndrome patients undergoing percutaneous coronary intervention. CCS, chronic coronary syndrome; MI, myocardial infarction; PCI, percutaneous coronary intervention.

We aimed to identify independent predictors of cardiac mortality and hospitalization for heart failure (HHF) from a real-world, multi-ethnic Asian registry [the Singapore Myocardial Infarction Registry] of ST-segment elevation myocardial infarction (STEMI) patients treated by primary percutaneous coronary intervention. 11,546 eligible STEMI patients between 2008 and 2015 were identified. In-hospital, 30-day and 1-year cardiac mortality and 1-year HHF rates were 6.4%, 6.8%, 8.3% and 5.2%, respectively. From the derivation cohort (70% of patients), age, Killip class and cardiac arrest, creatinine, hemoglobin and troponin on admission and left ventricular ejection fraction (LVEF) during hospitalization were predictors of in-hospital, 30-day and 1-year cardiac mortality. Previous ischemic heart disease (IHD) was a predictor of in-hospital and 30-day cardiac mortality only, whereas diabetes was a predictor of 1-year cardiac mortality only. Age, previous IHD and diabetes, Killip class, creatinine, hemoglobin and troponin on admission, symptom-to-balloon-time and LVEF were predictors of 1-year HHF. The c-statistics were 0.921, 0.901, 0.881, 0.869, respectively. Applying these models to the validation cohort (30% of patients) showed good fit and discrimination (c-statistic 0.922, 0.913, 0.903 and 0.855 respectively; misclassification rate 14.0%, 14.7%, 16.2% and 24.0% respectively). These predictors could be incorporated into specific risk scores to stratify reperfused STEMI patients by their risk level for targeted intervention.

Background In ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PPCI), current oral P2Y12 platelet inhibitors do not provide maximal platelet inhibition at the time of reperfusion. Furthermore, administration of cangrelor prior to reperfusion has been shown in pre-clinical studies to reduce myocardial infarct (MI) size. Therefore, we hypothesize that cangrelor administered prior to reperfusion in STEMI patients will reduce the incidence of microvascular obstruction (MVO) and limit MI size in STEMI patients treated with PPCI. Methods The platelet inhibition to target reperfusion injury (PITRI) trial, is a phase 2A, multi-center, double-blinded, randomized controlled trial, in which 210 STEMI patients will be randomized to receive either an intravenous (IV) bolus of cangrelor (30 μg/kg) followed by a 120-minute infusion (4 μg/kg/min) or matching saline placebo, initiated prior to reperfusion (NCT03102723). Results The study started in October 2017 and the anticipated end date would be July 2020. The primary end-point will be MI size quantified by cardiovascular magnetic resonance (CMR) on day 3 post-PPCI. Secondary endpoints will include markers of reperfusion, incidence of MVO, MI size, and adverse left ventricular remodeling at 6 months, and major adverse cardiac and cerebrovascular events. Summary The aim of the PITRI trial is to assess whether cangrelor administered prior to reperfusion would reduce acute MI size and MVO, as assessed by CMR.

AIMS We aimed to identify a 'frequent admitter' phenotype among patients admitted for acute decompensated heart failure (HF). METHODS AND RESULTS We studied 10 363 patients in a population-based prospective HF registry (2008-2012), segregated into clusters based on their 3-year HF readmission frequency trajectories. Using receiver-operating characteristic analysis, we identified the index year readmission frequency threshold that most accurately predicts HF admission frequency clusters. Two clusters of HF patients were identified: a high frequency cluster (90.9%, mean 2.35 ± 3.68 admissions/year) and a low frequency cluster (9.1%, mean 0.50 ± 0.81 admission/year). An index year threshold of two admissions was optimal for distinguishing between clusters. Based on this threshold, 'frequent admitters', defined as patients with ≥ 2 HF admissions in the index year (n = 2587), were of younger age (68 ± 13 vs 69 ± 13 years), more often male (58% vs. 54%), smokers (38.4% vs. 34.4%) and had lower left ventricular ejection fraction (37 ± 17 vs. 41 ± 17%) compared to 'non-frequent admitters' (

Smoking is one of the leading risk factors for cardiovascular diseases, including ischemic heart disease and hypertension. However, in acute myocardial infarction (AMI) patients, smoking has been associated with better clinical outcomes, a phenomenon termed the “smoker’s paradox.” Given the known detrimental effects of smoking on the cardiovascular system, it has been proposed that the beneficial effect of smoking on outcomes is due to age differences between smokers and non-smokers and is therefore a smoker’s pseudoparadox. The aim of this study was to evaluate the association between smoking status and clinical outcomes in ST-segment elevation (STEMI) and non-STEMI (NSTEMI) patients treated by percutaneous coronary intervention (PCI), using a national multi-ethnic Asian registry. In unadjusted analyses, current smokers had better clinical outcomes following STEMI and NSTEMI. However, after adjusting for age, the protective effect of smoking was lost, confirming a smoker’s pseudoparadox. Interestingly, although current smokers had increased risk for recurrent MI within 1 year after PCI in both STEMI and NSTEMI patients, there was no increase in mortality. In summary, we confirm the existence of a smoker’s pseudoparadox in a multi-ethnic Asian cohort of STEMI and NSTEMI patients and report increased risk of recurrent MI, but not mortality, in smokers.

Smoking is one of the leading risk factors for cardiovascular diseases, including ischemic heart disease and hypertension. However, in acute myocardial infarction (AMI) patients, smoking has been associated with better clinical outcomes, a phenomenon termed the “smoker’s paradox.” Given the known detrimental effects of smoking on the cardiovascular system, it has been proposed that the beneficial effects of smoking on outcomes is due to age differences between smokers and non-smokers and is therefore a smoker’s pseudoparadox. The aim of this study was to evaluate the association between smoking status and clinical outcomes in ST-segment elevation (STEMI) and non-STEMI (NSTEMI) patients treated by percutaneous coronary intervention (PCI), using a national multi-ethnic Asian registry. In unadjusted analyses, current smokers had better clinical outcomes following STEMI and NSTEMI. However, after adjusting for age, the protective effect of smoking was lost, confirming a smoker’s pseudoparadox. Interestingly, although current smokers had increased risk for recurrent MI within 1 year after PCI in both STEMI and NSTEMI patients, there was no increase in mortality. In summary, we confirm the existence of a smoker’s pseudoparadox in a multi-ethnic Asian cohort of STEMI and NSTEMI patients and report increased risk of recurrent MI, but not mortality, in smokers.

Protection against ischaemia–reperfusion injury after revascularisation in acute myocardial infarction remains an enigma. Many targets have been identified, but after the failure of the recent Effect of Remote Ischaemic Conditioning on Clinical Outcomes in ST-elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention (CONDI2/ERIC-PPCI) trial to show translation to clinical benefit, there is still no pharmacological or mechanical strategy that has translated to clinical practice. This article addresses the results of the CONDI2/ERIC-PPCI trial in the context of previous studies of ischaemic conditioning, and then considers the prospects for other potential targets of cardioprotection. Finally, the authors examine the pitfalls and challenges in trial design for future investigation of cardioprotective strategies. In particular, this article highlights the need for careful endpoint and patient selection, as well as the need to pay attention to the biology of cardioprotection during the study.

Background: Cut off values for change in left ventricular end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV) by cardiovascular magnetic resonance following ST-segment–elevation myocardial infarction have recently been proposed and 4 patterns of LV remodeling were described. We aimed to assess their long-term prognostic significance. Methods: A prospective cohort of unselected patients with ST-segment–elevation myocardial infarction with paired acute and 6-month cardiovascular magnetic resonance, with the 5-year composite end point of all-cause death and hospitalization for heart failure was included. The prognosis of the following groups (group 1: reverse LV remodeling [≥12% decrease in LVESV]; group 2: no LV remodeling [changes in LVEDV and LVESV Results: Two hundred eighty-five patients were included with a median follow-up was 5.8 years. The composite end point occurred in 9.5% in group 1, 12.3% in group 2, 7.1% in group 3, and 24.2% in group 4. Group 4 had significantly higher cumulative event rates of the composite end point (log-rank test, P =0.03) with the other 3 groups showing similar cumulative event rates (log-rank test, P =0.51). Cox proportional hazard for group 2 (hazard ratio, 1.3 [95% CI, 0.6–3.1], P =0.53) and group 3 (hazard ratio, 0.6 [95% CI, 0.2–2.3], P =0.49) were not significantly different but was significantly higher in group 4 (hazard ratio, 3.0 [95% CI, 1.2–7.1], P =0.015) when compared with group 1. Conclusions: Patients with ST-segment–elevation myocardial infarction developing adverse LV remodeling at 6 months, defined as ≥12% increase in both LVESV and LVEDV by cardiovascular magnetic resonance, was associated with worse long-term clinical outcomes than those with adverse LV remodeling with compensation, reverse LV remodeling, and no LV remodeling, with the latter 3 groups having similar outcomes in a cohort of stable reperfused patients with ST-segment–elevation myocardial infarction. Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT02072850.

Lowering low-density lipoprotein (LDL-C) and triglyceride (TG) levels form the cornerstone approach of cardiovascular risk reduction, and a higher high-density lipoprotein (HDL-C) is thought to be protective. However, in acute myocardial infarction (AMI) patients, higher admission LDL-C and TG levels have been shown to be associated with better clinical outcomes - termed the ‘lipid paradox’. We studied the relationship between lipid profile obtained within 72 hours of presentation, and all-cause mortality (during hospitalization, at 30-days and 12-months), and rehospitalization for heart failure and non-fatal AMI at 12-months in ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients treated by percutaneous coronary intervention (PCI). We included 11543 STEMI and 8470 NSTEMI patients who underwent PCI in the Singapore Myocardial Infarction Registry between 2008–2015. NSTEMI patients were older (60.3 years vs 57.7 years, p

Native myocardial T1 and extracellular volume (ECV) by cardiovascular magnetic resonance imaging are key biomarkers for assessing several heart muscle diseases. Their measurement, however, is influenced by blood T1, either due to myocardial vascular blood volume or via blood pool partial voluming.

Background Percutaneous coronary interventions on complex bifurcation lesions may require implantation of two stents to appropriately treat diffuse side-branch (SB) disease. Comparisons among different bifurcation stenting techniques are continuously attempted by various study designs (bench tests, computer simulations, clinical studies). Among different techniques, double kissing crush (DKC) represents the last evolution for “crushing” while T and small Protrusion (TAP) represents the evolution of “T stenting”. Both techniques are actually gaining popularity, but head-to-head comparisons are lacking. Methods and results Two last generation drug-eluting stents (Synergy™, Boston Scientific, MA, USA and Ultimaster™,Terumo Corp., Japan) were implanted in left main bifurcation bench models using TAP (n = 6 sets) and DKC (n = 6 sets) techniques. A peristaltic pump with fresh porcine blood was used to perfuse the blood through the silicone model at a flow rate of 200 ml/min for 4 min. Optical coherence tomography (OCT) was used to assess stent struts geometry and thrombus formation . SB cross sectional area as well as SB obstruction did not significantly differ between the two techniques. Numerical (but not statistically significant) differences were found in terms of malapposed struts (fewer with TAP) and floating struts (fewer with DKC). Thrombus formation after blood perfusion was similar between TAP and DKC technique (1.53 ± 1.12 vs. 1.20 ± 1.01 mm 2, p = 0.6). Conclusion The result of the present in-vitro study shows the absence of significant difference between TAP and DKC in terms of stent struts apposition and acute thrombus formation potential. Despite the completely different technical steps required, both techniques have similar performance according to such articulated pre-clinical evaluation. What is already known about this subject? Due to its limited complexity, T and Protrusion (TAP) technique is considered the to-go technique for bifurcation lesions with good long-term results. Recently, double kissing crush (DKC) technique has been gaining popularity and demonstrated promising results in randomized clinical trials. What does this study add? This in-vitro bench test study provides a unique detailed OCT comparison and local hemodynamic environment analysis of the two techniques. How might this impact on clinical practice? New insights of acute thrombogenicity and computational flow model simulation may guide percutaneous therapeutic strategies of bifurcation lesions.

Mortality after acute ST elevation myocardial infarction (STEMI) has declined over past decades, partly attributed to significant improvements in patient management. In this chapter, we provide an up-to-date review of the current evidence-based management of STEMI, starting at the time of first medical contact. It is now well established that ‘time is muscle’, and we begin by defining the various strategic time points that are crucial to minimize the total ischaemic time, a major determinant of clinical outcomes. We then cover the salient features of the management of STEMI patients before, during and immediately after reperfusion therapy by primary percutaneous coronary intervention or thrombolytic therapy. It is important to bear in mind that the management of STEMI patients does not stop after discharge from hospital. A multidisciplinary approach is required to address a range of other physical and social aspects, ranging from lifestyle modification and exercise-based rehabilitation to assessment for primary prevention implantable cardioverter-defibrillator and advice regarding driving.

Aims The optimal cut-off value of isolated cardiac biomarker elevation for defining prognostically important percutaneous coronary intervention (PCI)-related myocardial injury is not known. We performed a meta-analysis to evaluate the dose-response relationship between isolated cardiac biomarker elevations and the risk of all-cause mortality following elective PCI. Methods and results Twenty-four prospective studies (44,972 patients) were included. Patients with an isolated elevation of cardiac biomarkers had an increased risk of all-cause mortality when compared to those with no elevations (cardiac troponin I: odds ratio [OR] 1.42, 95% confidence interval [CI]: 1.19-1.69; creatine kinase-MB isoenzyme [CK-MB]: OR 1.43, 95% CI: 1.19-1.70). For the dose-response analysis, elevations of cardiac troponin I >3x or CK-MB >1x the 99th percentile upper reference limit (URL) were associated with increased mortality (cardiac troponin I: OR 1.51, 95% CI: 1.05-2.17; CK-MB: OR 1.25, 95% CI: 1.05-1.48). The pooled OR of mortality for each 3xURL increment of cardiac troponin I or CK-MB was 1.33 (95% CI: 1.15-1.53) and 1.38 (95% CI: 1.30-1.47). Conclusions We found that a positive dose-response relationship between isolated cardiac troponin I and CK-MB with all-cause mortality and elevated cardiac troponin I >3x or CK-MB >1x the 99th percentile URL was associated with an increased risk of mortality.

Prognosis in light-chain (AL) and transthyretin (ATTR) amyloidosis is influenced by cardiac involvement. ATTR amyloidosis has better prognosis than AL amyloidosis despite more amyloid infiltration, suggesting additional mechanisms of damage in AL amyloidosis.The aim of the study was to assess the presence and prognostic significance of myocardial edema in patients with amyloidosis.The study recruited 286 patients: 100 with systemic AL amyloidosis, 163 with cardiac ATTR amyloidosis, 12 with suspected cardiac ATTR amyloidosis (grade 1 onMyocardial T2 was increased in amyloidosis with the degree of elevation being highest in untreated AL patients (untreated AL amyloidosis 56.6 ± 5.1 ms; treated AL amyloidosis 53.6 ± 3.9 ms; ATTR amyloidosis 54.2 ± 4.1 ms; each p 0.01 compared with control subjects: 48.9 ± 2.0 ms). Left ventricular (LV) mass and extracellular volume fraction were higher in ATTR amyloidosis compared with AL amyloidosis while LV ejection fraction was lower (p 0.001). Histological evidence of edema was present in 87.5% of biopsy samples ranging from 5% to 40% myocardial involvement. Using Cox regression models, myocardial T2 predicted death in AL amyloidosis (hazard ratio: 1.48; 95% confidence interval: 1.20 to 1.82) and remained significant after adjusting for extracellular volume fraction and N-terminal pro-B-type natriuretic peptide (hazard ratio: 1.32; 95% confidence interval: 1.05 to 1.67).Myocardial edema is present in cardiac amyloidosis by histology and cardiovascular magnetic resonance T2 mapping. T2 is higher in untreated AL amyloidosis compared with treated AL and ATTR amyloidosis, and is a predictor of prognosis in AL amyloidosis. This suggests mechanisms additional to amyloid infiltration contributing to mortality in amyloidosis.

Background Cardiac transthyretin amyloidosis (ATTR) is an increasingly recognized cause of heart failure. Cardiac magnetic resonance (CMR), with late gadolinium enhancement (LGE) and T1 mapping, is emerging as a reference standard for diagnosis and characterization of cardiac amyloidosis. Objectives The authors used CMR with extracellular volume fraction (ECV) measurement to characterize cardiac involvement in relation to outcome in ATTR. Methods Subjects comprised 263 patients with cardiac ATTR corroborated by grade 2 to 3 99mTc-DPD (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid) cardiac uptake, 17 with suspected cardiac ATTR (grade 1 99mTc-DPD), and 12 asymptomatic individuals with amyloidogenic transthyretin (TTR) mutations. Fifty patients with cardiac light-chain (AL) amyloidosis acted as disease comparators. Results Unlike cardiac AL amyloidosis, asymmetrical septal left ventricular hypertrophy (LVH) was present in 79% of patients with ATTR (70% sigmoid septum and 30% reverse septal contour), whereas symmetrical LVH was present in 18%, and 3% had no LVH. In patients with cardiac amyloidosis, the pattern of LGE was always typical for amyloidosis (29% subendocardial, 71% transmural), including right ventricular LGE (96%). During follow-up (19 ± 14 months), 65 patients died. ECV independently correlated with mortality and remained independent after adjustment for age, N-terminal pro-B-type natriuretic peptide, ejection fraction, E/E′, and left ventricular mass (hazard ratio: 1.164; 95% confidence interval: 1.066 to 1.271; p Conclusions Asymmetrical hypertrophy, traditionally associated with hypertrophic cardiomyopathy, was the commonest pattern of ventricular remodeling in ATTR. LGE imaging was typical in all patients with cardiac ATTR. ECV correlated with amyloid burden and was an independent prognostic factor for survival in this cohort of patients.

We aimed to conduct an up-to-date meta-analysis to comprehensively assess the renoprotective effect of remote ischemic preconditioning (RIPC) in patients undergoing adult cardiac surgery. 21 randomized controlled trials (RCTs) with a total of 6302 patients were selected and identified. Compared with controls, RIPC significantly reduced the incidence of acute kidney injury (AKI) [odds ratio (OR) = 0.79; P = 0.02; I2 = 38%], and in particular, AKI stage I (OR = 0.65; P = 0.01; I2 = 55%). RIPC significantly shortened mechanical ventilation (MV) duration [weighted mean difference (WMD) = −0.79 hours; P = 0.002; I2 = 53%), and reduced intensive care unit (ICU) stay (WMD = −0.23 days; P = 0.07; I2 = 96%). Univariate meta-regression analyses showed that the major sources of heterogeneity for AKI stage I were age (coefficient = 0.06; P = 0.01; adjusted R2 = 0.86) and proportion of complex surgery (coefficient = 0.02; P = 0.03; adjusted R2 = 0.81). Subsequent multivariate regression and subgroup analyses also confirmed these results. The present meta-analysis suggests that RIPC reduces the incidence of AKI in adults undergoing cardiac surgery and this benefit was more pronounced in younger patients undergoing non-complex cardiac surgery. RIPC may also shorten MV duration and ICU stay. Future RCTs tailored for those most likely to benefit from RIPC warrants further investigation.

Cardiovascular magnetic resonance (CMR) has been used to assess the efficacy of novel cardioprotective therapies for reducing myocardial infarction (MI) size following ST-segment elevation MI. A recent preclinical study showed that the edema-based area at risk (AAR) is affected by certain

Background/Introduction Elevated levels of low-density lipoprotein (LDL-C) and triglycerides (TG) are well-described risk factors for the development of acute myocardial infarction (MI). Despite these well-established associations, previous studies have described the existence of a “lipid paradox” in acute MI patients – Patients paradoxically have worse outcomes despite having lower LDL-C and TG levels. Purpose We conducted this study to clarify the relationship of the lipid paradox and clinical outcomes amongst non-ST elevation (NSTEMI) and ST elevation MI (STEMI) patients in patients who have had percutaneous coronary intervention. Methods We included all acute MI patients reported to the Singapore Myocardial Infarction Registry from 2007 to 2013 who have had percutaneous coronary intervention. This information was linked to the national claims database to obtain the final discharge diagnosis for re-hospitalization outcomes. Exposure of interest was the lipid profile obtained within 72 hours of the acute MI (LDL-C, TG; Total cholesterol [TC]; high-density lipoprotein [HDL-C]). Primary outcomes were all-cause mortality during hospitalization, within 30-days and within 1-year. Secondary outcomes were re-hospitalization within 1-year for heart failure, stroke and MI. Results There were 8988 NSTEMI and 12453 STEMI cases available for analysis (n=21441). The NSTEMI patients were older (60.3 years vs 57.6 years, p Conclusion(s) An elevated LDL-C appears to be a protective prognostic marker in STEMI but not NSTEMI patients who have undergone percutaneous coronary intervention. This difference may be due to differing underlying pathophysiological mechanisms between the 2 populations.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden. The ERIC-PPCI trial was funded by a British Heart Foundation clinical study grant (grant number CS/14/3/31002) and a University College London Hospitals/University College London Biomedical Research Centre clinical research grant. The CONDI-2 trial was funded by Danish Innovation Foundation grants (grant numbers 11-108354 and 11-115818), Novo Nordisk Foundation (grant number NNF13OC0007447), and TrygFonden (grant number 109624). DJH was supported by the British Heart Foundation (grant number FS/10/039/28270), the National Institute for Health Research (NIHR) Biomedical Research Centre at University College London Hospitals, the Duke-National University Singapore Medical School, the Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist-Senior Investigator scheme (grant number NMRC/CSA-SI/0011/2017) and its Collaborative Centre Grant scheme (grant number NMRC/CGAug16C006), and the Singapore Ministry of Education Academic Research Fund Tier 2 (grant number MOE2016-T2-2-021). HEB was supported by the Novo Nordisk Foundation (grant numbers NNF14OC0013337, NNF15OC0016674). RKK is supported by the Oxford NIHR Biomedical Centre. The research was also supported by the NIHR infrastructure at Leeds. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health. This article is based on the work of COST Action EU-CARDIOPROTECTION (CA16225) and supported by COST (European Cooperation in Science and Technology). We thank all study personnel for their invaluable assistance. Sí

Primary percutaneous coronary intervention is nowadays the preferred reperfusion strategy for patients with acute ST-segment–elevation myocardial infarction, aiming at restoring epicardial infarct-related artery patency and achieving microvascular reperfusion as early as possible, thus limiting the extent of irreversibly injured myocardium. Yet, in a sizeable proportion of patients, primary percutaneous coronary intervention does not achieve effective myocardial reperfusion due to the occurrence of coronary microvascular obstruction (MVO). The amount of infarcted myocardium, the so-called infarct size, has long been known to be an independent predictor for major adverse cardiovascular events and adverse left ventricular remodeling after myocardial infarction. Previous cardioprotection studies were mainly aimed at protecting cardiomyocytes and reducing infarct size. However, several clinical and preclinical studies have reported that the presence and extent of MVO represent another important independent predictor of adverse left ventricular remodeling, and recent evidences support the notion that MVO may be more predictive of major adverse cardiovascular events than infarct size itself. Although timely and complete reperfusion is the most effective way of limiting myocardial injury and subsequent ventricular remodeling, the translation of effective therapeutic strategies into improved clinical outcomes has been largely disappointing. Of importance, despite the presence of a large number of studies focused on infarct size, only few cardioprotection studies addressed MVO as a therapeutic target. In this review, we provide a detailed summary of MVO including underlying causes, diagnostic techniques, and current therapeutic approaches. Furthermore, we discuss the hypothesis that simultaneously addressing infarct size and MVO may help to translate cardioprotective strategies into improved clinical outcome following ST-segment–elevation myocardial infarction.

We used multi-parametric cardiovascular magnetic resonance (CMR) mapping to interrogate the myocardium following ST-segment elevation myocardial infarction (STEMI). Forty-eight STEMI patients underwent CMR at 4 ± 2 days. One matching short-axis slice of native T1 map, T2 map, late gadolinium enhancement (LGE), and automated extracellular volume fraction (ECV) maps per patient were analyzed. Manual regions-of-interest were drawn within the infarcted, the salvaged and the remote myocardium. A subgroup analysis was performed in those without MVO and with ≤75% transmural extent of infarct. For the whole cohort, T1, T2 and ECV in both the infarcted and the salvaged myocardium were significantly higher than in the remote myocardium. T1 and T2 could not differentiate between the salvaged and the infarcted myocardium, but ECV was significantly higher in the latter. In the subgroup analysis of 15 patients, similar findings were observed for T1 and T2. However, there was only a trend towards ECVsalvage being higher than ECVremote. In the clinical setting, current native T1 and T2 methods with the specific voxel sizes at 1.5 T could not differentiate between the infarcted and salvaged myocardium, whereas ECV could differentiate between the two. ECV was also higher in the salvaged myocardium when compared to the remote myocardium.

Left ventricular hypertrophy (LVH), a common pathway in health and disease, occurs because of cellular hypertrophy and expansion of extracellular matrix. Myocardial biopsy can identify extracellular matrix expansion (fibrosis, amyloid) from cellular hypertrophy and disarray and infiltration (iron, amyloid, inflammatory cells), but its invasive nature restricts its use to specific cases. Histology recognizes these cellular (cell death/hypertrophy) and extracellular matrix (fibrosis/infiltration) processes, but conventional cardiac imaging combines them into 1 compartment: the left ventricular mass (LVM). Cardiovascular magnetic resonance (CMR) using T1 mapping can split LVM into cellular and matrix components by measuring the extracellular volume fraction (ECV). The cell volume is LVM/1.05×[1–ECV], and the matrix volume is LVM/1.05×ECV, 1.05 being the specific gravity of the myocardium. We used this approach to explore the biology of LVH. The study was approved by the ethical committee of the UK National Research Ethics Service (07/H0715/101) and conformed to the principles of the Helsinki Declaration. All subjects gave written consent to participate; 190 subjects underwent CMR, including healthy volunteers (HV; n=30, male 44%, 41±11 years of age, no cardiovascular history, and …

Objectives The authors sought to generate a synthetic extracellular volume fraction (ECV) from the relationship between hematocrit and longitudinal relaxation rate of blood. Background ECV quantification by cardiac magnetic resonance (CMR) measures diagnostically and prognostically relevant changes in the extracellular space. Current methodologies require blood hematocrit (Hct) measurement—a complication to easy clinical application. We hypothesized that the relationship between Hct and longitudinal relaxation rate of blood (R1 = 1/T1blood) could be calibrated and used to generate a synthetic ECV without Hct that was valid, user-friendly, and prognostic. Methods Proof-of-concept: 427 subjects with a wide range of health and disease were divided into derivation (n = 214) and validation (n = 213) cohorts. Histology cohort: 18 patients with severe aortic stenosis with histology obtained during valve replacement. Outcome cohort: For comparison with external outcome data, we applied synthetic ECV to 1,172 consecutive patients (median follow-up 1.7 years; 74 deaths). All underwent CMR scanning at 1.5-T with ECV calculation from pre- and post-contrast T1 (blood and myocardium) and venous Hct. Results Proof-of-concept: In the derivation cohort, native R1blood and Hct showed a linear relationship (R2 = 0.51; p Conclusions Synthetic ECV provides validated noninvasive quantification of the myocardial extracellular space without blood sampling and is associated with cardiovascular outcomes.

We read with great interest the pooled analysis by Garcia-Garcia et al. ([1][1]) on the impact of periprocedural biomarker elevation on mortality following elective percutaneous coronary intervention. Data were obtained from 5 randomized controlled trials and 1 registry (13,452 patients). Creatine

The use of bioresorbable stents in interventional cardiology presents a novel approach in the treatment of coronary artery disease. The bioresorbable technology was introduced to overcome limitations of current metallic drug-eluting stents such as late in-stent restenosis and permanently caging the vessel. The concept of a bioresorbable stent is to provide temporal support to the vessel before being degraded and resorbed by the body, promoting vessel healing and restoration of vasomotion. Although the bioresorbable stents have many promising advantages over metallic stents, drawbacks such as insufficient radial strength of the bioresorbable material and large strut profile of the stent need to be addressed in order to enhance the performance of the bioresorbable stents. Currently, there are several bioresorbable scaffolds that are under development with some already commercially available. In this chapter, the concept of bioresorbable stents together with its advantages and limitations will be examined. An overview of the current bioresorbable platforms which include bioresorbable scaffolds made from polymers and biodegradable metallic stents will also be discussed.

We read with great interest the recent paper by De Maria et al. [(1)][1] investigating the concordance and discordance between index of microvascular resistance (IMR) at the time of primary percutaneous coronary intervention (PPCI) and microvascular obstruction (MVO) by cardiovascular magnetic

The rationale and study design for the multicentre, randomized, controlled CONDI2/ERIC-PPCI study are discussed.