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Identifying the culprit during inferior myocardial infarction (MI) is still challenging. We determined the diagnostic effect of electrocardiographic (ECG) indices in identifying the culprit vessel of acute MI and the impact of coronary artery dominance on it. This cross-sectional study included patients with acute inferior MI who presented to Imam Khomeini Hospital and Tehran Heart Center and underwent primary PCI within 12 h of the onset of symptoms. A standard 12‑lead ECG was recorded and interpreted by two cardiologists. Based on the coronary angiography, the patients were divided into two groups of LCX or RCA involvement and were compared for general variables and ECG indices. The diagnostic values of the ECG indices for predicting the culprit vessel were then calculated. We evaluated 411 patients with inferior STEMI (321 [77.5%] male, age 58.1 ± 11.1 years). RCA was the culprit vessel in 286 patients (69.1%) and LCX in 128 patients (30.9%). 321 patients (77.5%) were right dominant, 40 (9.7%) patients were left dominant, and 53 patients (12.8%), were codominant. Coronary dominance had minimal impact on the ECG indices regarding culprit identification even after adjustment for confounders. STE in lead III > lead II had the highest sensitivity for detecting RCA as the culprit (sensitivity: 89.2% and specificity: 57.8%). STE ≥0.1 mV in V5 or V6 leads had the highest sensitivity for detecting LCX as the culprit (sensitivity: 51.6, specificity: 93.7%). In inferior STEMI, ECG indices can predict the culprit vessel with acceptable sensitivity and specificity independent of coronary artery dominance. [ABSTRACT FROM AUTHOR]

The "2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Patients With Atrial Fibrillation" provides recommendations to guide clinicians in the treatment of patients with atrial fibrillation. A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" and the "2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed. [ABSTRACT FROM AUTHOR]

• Myocardial infarction with non-obstructive coronary arteries (MINOCA) constitutes a significant proportion of patients who are at excess cardiovascular risk and have adverse clinical outcomes. • Coronary microvascular dysfunction (CMD) plays a potential role in the pathogenesis of MINOCA and may affect clinical outcomes, however, the role of functional and structural mechanisms of CMD in MINOCA remains unknown. • CMD can be assessed by various invasive and non-invasive tools depending on availability and clinical settings. • A better understanding of CMD in MINOCA has significant clinical implications for decision-making, identifying novel therapies that target CMD and improve clinical outcomes. In the past decade, scientific and clinical research has provided a translational perspective on myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA). MINOCA is characterized by clinical documentation of an acute MI but angiography shows no significant coronary artery obstruction (stenosis <50%). The prevalence of MINOCA is estimated to range from approximately 6 to 10% among MI patients, and those with this condition have a poor prognosis, experiencing high rates of mortality, rehospitalization, and socioeconomic burden. MINOCA represents a major unmet need in cardiovascular medicine, with uncertain clinical management. It is a complex condition that can be caused by various factors, including atherosclerosis, plaque rupture, coronary vasospasm, and microvascular dysfunction. Effective management of MINOCA depends on identifying the underlying mechanism of the infarction, thus a systematic diagnostic approach is recommended. Contemporary data shows that a significant number of patients exhibit structural and functional abnormalities in coronary microcirculation, which is referred to as coronary microvascular dysfunction (CMD). CMD plays a crucial role in patients with signs and symptoms of myocardial ischemia and non-obstructive coronary artery stenosis, including MINOCA. Furthermore, conducting a thorough evaluation of coronary function can have significant prognostic and therapeutic implications, since personalized patient management strategies based on this assessment have been shown to improve symptoms and prognosis. Therefore, an accurate and timely diagnosis of CMD is essential for effective patient management, which can be achieved through various invasive and non-invasive methods. This review will discuss the pathophysiological understanding, current diagnostic techniques, and management strategies of patients with MINOCA and CMD. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Ventricular septal rupture (VSR) is a rare but life-threatening complication of ST-elevation myocardial infarction. Point-of-care ultrasound (POCUS) is a rapid, noninvasive imaging modality that is easily accessible and highly effective in diagnosing VSR in the emergency department (ED) setting.Case Report: A 73-year-old man with a history of type II diabetes mellitus and hypertension presented with complaints of intermittent chest pain for 48 h that had since become constant, associated with diaphoresis and shortness of breath. Physical examination was notable for shock and a new, grade V/VI systolic murmur. An electrocardiogram showed evidence of an inferior ST-elevation myocardial infarction (MI) with associated Q waves. POCUS revealed a large ventricular septal rupture with new ventricular septal defect and associated left-to-right shunting. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: POCUS in the ED setting is an effective and rapid tool for elucidating the etiology of various shock states. Emergency physicians should be aware of this particular case, as POCUS may help identify MI-related complications, including post-myocardial infarction VSR, that may necessitate surgical intervention as opposed to coronary reperfusion procedures. [ABSTRACT FROM AUTHOR]

• Diagnosis of MINOCA (e.g. coronary spasm) is important to avoid unnecessary PCI. • Sufficient coronary dilatation is crucial, but accurate diagnosis may be still challenging. • Intravascular imaging such as IVUS or OCT can help determine the exact cause of Acute Myocardial Infarction. [ABSTRACT FROM AUTHOR]

The transradial approach for cardiac catheterization, coronary angiography, and percutaneous intervention is associated with a lower risk of access site-related complications compared to the transfemoral approach. However, with increasing utilization of transradial access for not only coronary procedures but also peripheral vascular procedures, healthcare personnel are more likely to encounter radial access site complications, which can be associated with morbidity and mortality. There is significant heterogeneity in the reporting of incidence, manifestations, and management of radial access site complications, at least partly due to vague presentation and under-diagnosis. Therefore, physicians performing procedures via transradial access should be aware of possible complications and remain vigilant to prevent their occurrence. Intraprocedural complications of transradial access procedures, which include spasm, catheter kinking, and arterial dissection or perforation, may lead to patient discomfort, increased procedure time, and a higher rate of access site cross over. Post-procedural complications such as radial artery occlusion, hematoma, pseudoaneurysm, arteriovenous fistula, or nerve injury could lead to patient discomfort and limb dysfunction. When radial access site complications occur, comprehensive evaluation and prompt treatment is necessary to reduce long-term consequences. In this report, we review the incidence, clinical factors, and management strategies for radial access site complications associated with cardiac catheterization. [ABSTRACT FROM AUTHOR]

Background: This study aimed to use the Charlson Comorbidity Index (CCI) to assess the prevalence of medical comorbidities among hospitalization episodes with a primary Bipolar Disorder (BD) diagnosis, and to analyze its association with hospitalization outcomes.Methods: A population-based observational retrospective study was conducted using a Portuguese administrative database containing all mainland public hospitalizations. From 2008-2015, hospitalization episodes with a primary diagnosis of BD were analysed. Outcomes included: length of stay (LoS), in-hospital mortality and discharge destination.Results: Overall, 20807 hospitalization episodes were analysed. Mean±standard deviation age at admission was 47.9±14.3 years, and these episodes mostly refer to women's admissions (66.6%). Median (1st quartile; 3rd quartile) LoS was 16.0 (9.0; 25.0) days. A total of 2145 (10.3%) episodes had ≥1 CCI comorbidities registered, being diabetes the most prevalent. LoS was significantly higher for episodes with secondary diagnoses of congestive heart failure, cerebrovascular disease, dementia, diabetes, renal disease and malignancy (all p<0.05). Episodes with a registry of myocardial infarction, peripheral vascular disease, malignancy and renal disease diagnoses had higher in-hospital mortality.Limitations: Limitations include the use of data registered for administrative reasons rather than research purposes, and the analysis of hospitalization episodes, instead of patients.Conclusions: In this Portuguese nationwide study, greater comorbidity had a measurable impact on BD hospitalization outcomes. During the study period the prevalence of CCI comorbidities rose from 8.1% to 17.4%, which may reflect the overall increasing quality of hospital-coded data in Portugal throughout the years. The detection and timely management of medical comorbid conditions will likely prevent the high BD medical burden. [ABSTRACT FROM AUTHOR]

• A pre-trained 3D Autoencoder is used to reconstruct an identity segmentation result. • Optimum setting parameters are useful for segmentation and computational performance. • Propose volume patch extraction from Delayed Enhancement Magnetic Resonance Imaging. • A fusion of 3D Autoencoder with 3D U-Net proves better myocardial segmentation. • An anatomical network is used to segment the myocardium and left ventricular cavity. Objectives: In this work, a new deep learning model for relevant myocardial infarction segmentation from Late Gadolinium Enhancement (LGE)-MRI is proposed. Moreover, our novel segmentation method aims to detect microvascular-obstructed regions accurately. Material and methods: We first segment the anatomical structures, i.e., the left ventricular cavity and the myocardium, to achieve a preliminary segmentation. Then, a shape prior based framework that fuses the 3D U-Net architecture with 3D Autoencoder segmentation framework to constrain the segmentation process of pathological tissues is applied. Results: The proposed network reached outstanding myocardial segmentation compared with the human-level performance with the average Dice score of '0.9507' for myocardium, '0.7656' for scar, and '0.8377' for MVO on the validation set consisting of 16 DE-MRI volumes selected from the training EMIDEC dataset. Conclusion: It is concluded that our approach's extensive validation and comprehensive comparison against existing state-of-the-art deep learning models on three annotated datasets, including healthy and diseased exams, make this proposal a reliable tool to enhance MI diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: The diagnosis or exclusion of obstructive stable coronary artery disease (SCAD) in clinical practice is challenging and therefore clinical guidelines provide recommendations on the use of non-invasive and invasive testing. For Germany, data obtained from the OECD and health insurances indicate a potential non-adherence to guideline-recommended diagnostic pathways. However, there is a lack of prospective and reliable evidence for appropriate use of invasive coronary angiography (CA) in Germany.Objective: To provide evidence on the nature and extent of guideline non-adherence in patients undergoing CA with presumed obstructive SCAD in Germany and, to evaluate the clinical and economic consequences of potential deviations in guideline adherence.Methods: ENLIGHT-KHK is a multicentre, prospective observational study recruiting 1500 patients being admitted for CA with presumed obstructive SCAD and exclusion of acute myocardial infarction (DRKS00015638). The primary outcome measure is the adherence to clinical guidelines in the decision-making process for use of CA. Therefore, the patients' diagnostic pathways and adherence to German and European guidelines will be assessed using clinical data, health-claims data, and a patient questionnaire. The primary safety outcome is a composite of myocardial infarction, stroke and all-cause death. Secondary outcome measures are periprocedural complications and costs. Using a decision-analytic model, the clinical and economic impact of observed guideline adherence in clinical practice will be assessed. Potential barriers and facilitators of guideline-adherent decision-making will be evaluated via semi-structured interviews.Conclusions: ENLIGHT-KHK will give insights into the appropriateness of invasive CA in Germany and enable the development of concepts to improve guideline-adherence in the German health-care setting. [ABSTRACT FROM AUTHOR]

• GCA-related myocardial infarction (MI) is a rare event (2.4% of cases). • GCA-related MI are mainly type 2 MI rather than type 1 MI due to coronary artery disease. • GCA-unrelated MI are predominantly type 1 MI with atherothrombotic coronary artery disease. Cardiovascular risk is increased in giant cell arteritis (GCA). We aimed to characterize myocardial infarction (MI) in a GCA cohort, and to compare the GCA and non-GCA population affected by MI. In patients with a biopsy-proven diagnosis of GCA between 1 January 2001 and 31 December 2016 in Côte D'Or (France), we identified patients with MI by crossing data from the territorial myocardial infarction registry (Observatoire des Infarctus de Côte d'Or) database. Five controls (non-GCA + MI) were paired with one case (GCA + MI) after matching for age, sex, cardiovascular risk factors and prior cardiovascular disease. MI were characterized as type 1 MI (T1MI), resulting from thrombus formation due to atherothrombotic disease, or type 2 MI (T2MI), due to a myocardial supply/demand mismatch. GCA-related MI was defined as MI occurring within 3 months of a GCA flare (before or after). Among 251 biopsy-proven GCA patients, 13 MI cases were identified and paired with 65 controls. MI was GCA-related in 6/13 cases, accounting for 2.4% (6/251) of our cohort. T2MI was more frequently GCA-related than GCA-unrelated (80% vs. 16.7%, p = 0.080), and GCA diagnosis was the only identified triggering factor in 75% of GCA-related T2MI. GCA-unrelated MI were more frequently T1MI and occurred in patients who had received a higher cumulative dose of prednisone (p = 0.032). GCA was not associated with poorer one-year survival. GCA-related MI are mainly T2MI probably caused by systemic inflammation rather than coronaritis. GCA-unrelated MI are predominantly T1MI associated with atherothrombotic coronary artery disease. [ABSTRACT FROM AUTHOR]

Background: Limited U.S. data exist regarding high-sensitivity cardiac troponin (cTn) implementation.Objectives: This study sought to evaluate the impact of high-sensitivity cardiac troponin T (cTnT) implementation.Methods: Observational U.S. cohort study of emergency department (ED) patients undergoing measurement of cTnT during the transition from 4th (pre-implementation March 12, 2018, to September 11, 2018) to 5th generation (Gen) cTnT (post-implementation September 12, 2018, to March 11, 2019). Diagnoses were adjudicated following the Fourth Universal Definition of Myocardial Infarction (MI). Resources evaluated included length of stay, hospitalizations, and cardiac testing.Results: In this study, 3,536 unique patients were evaluated, including 2,069 and 2,491 ED encounters pre- and post-implementation. Compared with 4th Gen cTnT, encounters with ≥1 cTnT >99th percentile increased using 5th Gen cTnT (15% vs. 47%; p < 0.0001). Acute MI (3.3% vs. 8.1%; p < 0.0001) and myocardial injury (11% vs. 38%; p < 0.0001) increased. Although type 1 MIs increased (1.7% vs. 2.9%; p = 0.0097), the overall MI increase was largely due to more type 2 MIs (1.6% vs. 5.2%; p < 0.0001). Women were less likely than men to have MI using 4th Gen cTnT (2.3% vs. 4.4%; p = 0.008) but not 5th Gen cTnT (7.7% vs. 8.5%; p = 0.46). Overall length of stay and stress testing were reduced, and angiography was increased (all p < 0.05). Among those without cTnT increases, there were more ED discharges and a reduction in length of stay, echocardiography, and stress tests (all p < 0.05).Conclusions: High-sensitivity cTnT implementation resulted in a marked increase in myocardial injury and MI, particularly in women and patients with type 2 MI. Despite this, except for angiography, overall resource use did not increase. Among those without cTnT increases, there were more ED discharges and fewer cardiac tests. [ABSTRACT FROM AUTHOR]

Acetylcholine (ACh) provocation testing can detect vasomotor disorders in patients with ischemia and non-obstructed coronary arteries (INOCA) or myocardial infarction and non-obstructed coronary arteries (MINOCA). We aimed to derive and validate a simple risk score to predict a positive ACh test response. We prospectively enrolled consecutive INOCA and MINOCA patients undergoing ACh provocation testing. Patients were split in two cohorts (derivation and validation) according to time of enrolment. The score was derived in 386 patients (derivation cohort) and then validated in 165 patients (validation cohort). 551 patients were enrolled, 371 (67.3%) INOCA and 180 (32.7%) MINOCA. ACh test was positive in 288 (52.3%) patients. MINOCA, myocardial bridge (MB), C-reactive protein (CRP) and dyslipidaemia were independent predictors of a positive ACh test in the derivation cohort. The ABCD (Acute presentation, Bridge, CRP, Dyslipidaemia) score was derived: 2 points were assigned to MINOCA, 3 to MB, 1 to elevated CRP and 1 to dyslipidaemia. The ABCD score accurately identified patients with a positive ACh test response with an AUC of 0.703 (CI 95% 0.652–0.754, p < 0.001) in the derivation cohort, and 0.705 (CI 95% 0.626–0.784, p < 0.001) in the validation cohort. In the whole population, an ABCD score ≥4 portended 94.3% risk of a positive ACh test and all patients with an ABCD score ≥6 presented a positive test. The ABCD score could avoid the need of ACh provocation testing in patients with a high score, reducing procedural risks, time, and costs, and allowing the implementation of a tailored treatment strategy. These results are hypothesis generating and further research involving larger cohorts and multicentre trials is needed to validate and refine the ABCD score. [Display omitted] • Acetylcholine provocation testing is still largely underused, leading to inappropriate medical therapies and worse outcomes. • The ABCD score demonstrated high specificity in identifying patients likely to have a positive acetylcholine test response. • Performing the test could be avoided in patients with high scores (i.e., ≥4), reducing procedural risks, time, and costs. [ABSTRACT FROM AUTHOR]

Circadian rhythms follow a 24 h day and night cycle, regulate vital physiological processes, and are especially relevant to cardiovascular growth, renewal, repair, and remodeling. A recent flurry of clinical and experimental studies reveals a profound circadian influence on immune responses in cardiovascular disease. The first section of this review summarizes the importance of circadian rhythms for cardiovascular health and disease. The second section introduces the circadian nature of inflammatory responses. The third section combines these to elucidate a new role for the circadian system, influencing inflammation in heart disease, especially myocardial infarction. Particular focus is on circadian regulation of the NACHT, LRR, and PYD domains–containing protein 3 inflammasome, neutrophils, monocytes/macrophages, and T cells involved in cardiac repair. A role for biological sex is noted. The final section explores circadian influences on inflammation in other major cardiovascular conditions. Circadian regulation of inflammation has profound implications for benefitting the diagnosis, treatment, and prognosis of patients with cardiovascular disease. [ABSTRACT FROM AUTHOR]

Optimal timing of antithrombotic therapy for patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) is unclear. We analyzed the impact of pre-angioplasty administration of unfractionated heparin (UFH) on infarct-related artery (IRA) patency and mortality. Multicenter prospective observational study of 3520 STEMI patients treated with PPCI from 2016 to 2018. Subjects were divided into four groups according to the elapsed time from heparin administration to PPCI: Group 1: Upon arrival at catheterization laboratory or ≤ 30 min (n = 800; 22.7%); Group 2: 31 to 60 min (n = 994; 28.2%); Group 3: 61 to 90 min (n = 1091; 31%); Group 4: >90 min (n = 635; 18%). IRA patency was defined as thrombolysis in myocardial infarction (TIMI) flow grade 2–3. Multivariate analyses assessed factors associated with IRA patency and both 30-day and 1-year mortality. UFH administration at STEMI diagnosis was an independent predictor of IRA patency especially when administered more than 60 min before the PPCI (OR 1.43; 95% CI 1.14–1.81), either an independent predictor of 30-day (HR 0.63; 95% CI 0.42–0.94) and 1-year (HR 0.57; 95% CI 0.41–0.80) mortality. The effect of UFH on IRA patency was higher when administered earlier from the symptom onset. UFH administration at STEMI diagnosis improves coronary reperfusion prior to PPCI and this benefit seems associated with superior clinical outcomes. The presented results highlight a time-dependent effectiveness of UFH, since its reported effect is greater the sooner UFH is administered after symptom onset. • Association between early pre-angioplasty UFH administration in STEMI patients and IRA patency and mortality were evaluated. • UFH administration at STEMI diagnosis before PPCI improved pre-angioplasty coronary patency. • This effect was greater the sooner UFH was administered after symptoms onset. • UFH administration can be associated with decreased 30-day and 1-year mortality due to an earlier coronary reperfusion. • Combining UFH with novel P2Y12 inhibitors did not increase the rate of reperfusion before PPCI. [ABSTRACT FROM AUTHOR]

A first-time acute myocardial infarction (AMI) is a severe diagnosis that leads to initiation or intensification of lipid-lowering medication to prevent recurrent events. Individuals with familial hypercholesterolemia (FH) already use high-intensity lipid-lowering medication at the time of an incident AMI due to their diagnosis. Hence, we hypothesized that compared with matched non-FH controls, individuals with genetically verified FH have increased mortality and risk of recurrent AMI after their first event. The study population comprised 4871 persons with genetically verified FH, and 96,251 age and sex matched controls randomly selected from the Norwegian population. Data were obtained from the Cardiovascular Disease in Norway Project, the Norwegian Patient Registry and the Norwegian Cause of Death Registry. Incidence of AMI, all-cause mortality and recurrent AMI after incident AMI were analyzed for the period 2001–2017. Incidence and mortality were compared using hazard ratios (HR) from Cox regression. Risk of recurrent AMI was compared using sub-hazard ratios (SHR) from competing risk regression with death as a competing event. We identified 232 individuals with FH and 2118 controls with an incident AMI [HR 2.10 (95% CI 1.83–2.41)]. Among survivors ≥29 days after the incident AMI, both mortality [HR = 1.45 (95% CI: 1.07–1.95)] and recurrent AMI [SHR = 2.53 (95% CI: 1.88–3.41)] were significantly increased among individuals with FH compared with non-FH controls. Individuals with FH have increased mortality and increased risk of recurrent AMI after the first AMI event compared with controls. These findings call for intensive follow-up of individuals with FH following an AMI. Image 1 • Individuals with genetically verified familial hypercholesterolemia (FH) have poorer prognosis after incident acute myocardial infarction (AMI). • 2.5-fold increased risk of recurrent AMI with FH. • 45% increased risk of dying after an incident acute myocardial infarction with FH. • Need for more close monitoring of individuals with FH following acute myocardial infarction. [ABSTRACT FROM AUTHOR]

To explore the significance of circulating miRNA-1 (miR-1) released within 3 h after the onset of acute chest pain in the diagnosis and prognosis of acute myocardial infarction (AMI). A total of 337 patients with acute chest pain within 3 h were enrolled in this study and divided into AMI group and non-AMI group. The AMI diagnostic efficacy of miR-1 was determined and compared with that of cardiac troponin I (cTnI). The patients were followed up for 720 d after treatment. The significance of circulating miR-1 in AMI prognosis was assessed using univariate and COX regression analysis. There were 174 patients in AMI group, 163 in non-AMI group. Circulating miR-1 level was significantly higher in AMI group than in non-AMI group (P < 0.001). The AMI diagnostic efficacy of miR-1 and cTnI were similar (P > 0.05). We established two AMI diagnostic models, the AUC values of which were larger than that of cTnI or miR-1 (P < 0.05). When miR-1 combined with CK-MB, cTnI, and other clinical and laboratory parameters (model 2), the AUC was the largest (AUC: 0.961) and had the highest diagnostic efficiency. Circulating miR-1, Killip classification, and treatment method were influencing factors for AMI prognosis (P < 0.05). Circulating miR-1 within 3 h of acute chest pain has the potential diagnostic value for AMI, and which is an independent risk factor for the prognosis of AMI and can be used to predict AMI prognosis. • Blood samples were collected within 3 h after the onset of the acute chest pain. • Mathematical models for early diagnosis of AMI were established by using miR-1. • MiR-1 was one of the independent prognostic factors of AMI. [ABSTRACT FROM AUTHOR]

Patients with familial hypercholesterolemia (FH) have an increased risk of premature myocardial infarction (MI). The objective of the study is to investigate the prevalence of FH among young patients hospitalized with acute MI. Data were collected from medical charts of all patients aged <45 years admitted with acute MI to the Department of Cardiology, Oslo University Hospital Ullevål, in the period 2012 to 2016. Patients who had not already been genetically tested for FH were contacted and offered genetic testing if the pretreatment or the statin-adjusted low-density lipoprotein cholesterol level was >4.0 mmol/L (155 mg/dL). Of 9332 patients admitted with acute MI, 357 were aged <45 years. Sixteen patients were deceased, and 13 patients did not have MI on an atherosclerotic basis. Of the remaining 328 patients eligible for investigation, 130 had the pretreatment or statin-adjusted low-density lipoprotein cholesterol level >4.0 mmol/L (155 mg/dL). Of these, data from 52 patients genetically tested for FH were available. Eleven patients had genetically verified FH constituting 3.4% of the total eligible population (n = 328), 8.5% of those with indications for genetic testing (n = 130), and 21.2% of those actually tested (n = 52). A Dutch Lipid Clinic Network score for clinical FH diagnosis of "definite FH" identified only 5 of the 11 patients with positive genetic test (45%). Including a score of "probable FH" identified all patients with FH but also 17 of the 41 patients (41%) with a negative genetic test. The prevalence of FH in young patients with acute MI was higher than in the general population. Routine evaluation of FH diagnosis among these patients could identify more patients with FH, thereby increasing the possibility of initiating early and adequate treatment also among affected relatives. • Three hundred twenty-eight patients aged <45 years had myocardial infarction (MI); 130 had low-density lipoprotein cholesterol level >4.0 mmol/L (155 mg/dL). • 52 patients were genetically tested, of whom 11 had a positive genetic test. • Prevalence of familial hypercholesterolemia (FH) in young patients with MI was higher than in the general population. • Routine evaluation of FH in patients with MI could identify more patients with FH. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) not only defines acute MI with obstructed coronary arteries (T1MI) but also myocardial necrosis caused by myocardial oxygen supply/demand mismatch as type 2 MI (T2MI); only T1MI patients benefit from an early invasive management. Myeloid-related protein(MRP)-8/14 is a biomarker described in various inflammatory diseases and in MI patients. Here we evaluate the potential of MRP-8/14 and high-sensitivity troponin I (hs-cTnI) to differentiate T2MI from T1MI. Patients with final diagnosis NSTEMI (n = 254; 33.1% female) enrolled in a prospective biomarker registry between 08/2011 and 10/2016 were analysed. Median baseline MRP-8/14 levels were higher in T2MI (n = 55; 3.37(1.88–6.48)μg/mL) than in T1MI (n = 199; 2.4 [1.4–3.79]μg/mL) (p =.013) patients, in contrast to hs-cTnI (T2MI:52[11.65–321.4]ng/L vs. T1MI:436.5 [61.25–1973.8]ng/L; p <.001). To detect the strength of this association odds ratios(OR) were calculated with MRP-8/14 yielding 2.13(1.16–3.92; p =.015) to predict T2MI and 0.47(0.26–0.87; p =.015) for T1MI. As expected, hs-cTnI yielded an OR of to predict T2MI 0.34(0.17–0.65; p =.001) and 2.98(1.53–5.81; p =.001) for T1MI. Both markers show comparable and independent results if adjust to hs-cTnI/MRP-8/14, TIMI risk score and CRP. T2MI is associated with higher MRP-8/14 and lower hs-cTnI concentrations than T1MI. Our data suggest that MRP-8/14 as a marker of inflammation might provide usable discriminatory information complementing hs-cTnI in a diagnostic procedure evaluating the type of MI directly upon hospital admission. • Early differentiation of MI type is crucial for an adequate treatment. • Myeloid-related protein 8/14 levels are elevated in type 2 MI. • Troponin I shows highest values in type 1 MI. • Both provide independent diagnostic information that might amend clinical decision algorithms. [ABSTRACT FROM AUTHOR]

Magnetic field maps from (A) subjects without ischemia, showing a bipolar field map throughout the cardiac cycle, and (B) patients with acute coronary syndrome in whom a distorted, fragmented or multipolar field map characterizes active myocardial ischemia. Maps were recorded with a 15-channel magnetometry device and display the magnetic field distribution at the point of maximum rate of change between the Q and R peaks (QR) and between the R and S peaks (RS). Unlabelled Image The dipoles observed in subjects without ischemia are generally aligned in the same direction and have only a single positive (red) and single negative (blue) pole. The images from ischemic patients are generally more complex. A wider spread of angles and pole to pole distance, and the presence of more than two peaks are features that generally indicate ischemia. [ABSTRACT FROM AUTHOR]

• There is no review summarizing biomarkers in MINOCA. • We summarized the non-atherosclerotic biomarkers, including traditional markers, potential markers, and imaging markers. • Biomarkers of MINOCA are of great significance for diagnosis, treatment, prognosis and mechanism research. Myocardial infarction in the absence of obstructive coronary artery disease (MINOCA) is an important subtype of myocardial infarction. Although comprising less than 50% stenosis in the main epicardial coronary arteries, it constitutes a severe health risk. A variety of approaches have been recommended, but definitive diagnosis remains elusive. In addition, the lack of a comprehensive understanding of underlying pathophysiology makes clinical management difficult and unpredictable. This review highlights ongoing efforts to identify relevant biomarkers in MINOCA to improve diagnosis, individualize treatment and better predict outcomes. [ABSTRACT FROM AUTHOR]

To assess the incremental contribution of preoperative stress test results toward a diagnosis of obstructive coronary artery disease (CAD), prediction of mortality, or prediction of perioperative myocardial infarction in patients considering noncardiac, nonophthalmologic surgery. A retrospective cohort study of visits to a preoperative risk assessment and optimization clinic in a large health system between 2008 and 2018. To assess diagnostic information of preoperative stress testing, we used the Begg and Greenes method to calculate test characteristics adjusted for referral bias, with a gold standard of angiography. To assess prognostic information, we first created multiply-imputed logistic regression models to predict 90-day mortality and perioperative myocardial infarction (MI), starting with two tools commonly used to assess perioperative cardiac risk, Revised Cardiac Risk Index (RCRI) and Myocardial Infarction or Cardiac Arrest (MICA). We then added stress test results and compared the discrimination for models with and without stress test results. Among 136,935 visits by patients without an existing diagnosis of CAD, the decision to obtain preoperative stress testing identified around 4.0% of likely new diagnoses. Stress testing increased the likelihood of CAD (likelihood ratio: 1.31), but for over 99% of patients, stress testing should not change a decision on whether to proceed to angiography. In 117,445 visits with subsequent noncardiac surgery, stress test results failed to improve predictions of either perioperative MI or 90-day mortality. Reweighting the models and adding hemoglobin improved the prediction of both outcomes. Cardiac stress testing before noncardiac, nonophthalmologic surgery does not improve predictions of either perioperative mortality or myocardial infarction. Very few patients considering noncardiac, nonophthalmologic surgery have a pretest probability of CAD in a range where stress testing could usefully select patients for angiography. Better use of existing patient data could improve predictions of perioperative adverse events without additional patient testing. • The pretest probability of obstructive coronary artery disease is very low in patients considering noncardiac surgery. • Even with careful patient selection, stress testing can't efficiently diagnose CAD or select patients for angiography. • Stress test results don't improve predictions of death or myocardial infarction beyond commonly-used risk scores. • Prediction models that make better use of existing data could improve predictions of adverse operative events. [ABSTRACT FROM AUTHOR]

Pheochromocytomas or paragangliomas are rare and the diagnosis remains a challenge for clinicians. We present a woman suffering from recurrent myocardial infarction and cardiomyopathy, who was finally diagnosed with paraganglioma. Pheochromocytomas or paraganglioma should be considered in the differential diagnosis of a patient with symptoms possibly referring to acute coronary syndrome and cardiomyopathy. [ABSTRACT FROM AUTHOR]

Abstract Background We aimed to evaluate the diagnostic sensitivity for myocardial infarction (MI) when using an undetectable level of high-sensitivity cardiac troponin T (hs-cTnT < 5 ng/L) at presentation combined with a non-ischemic electrocardiogram (ECG), to rule out MI in a non-ST-segment elevation MI (NSTEMI) cohort presenting ≤2 h from symptom onset. We also aimed to compare baseline characteristics and 30-day outcome in NSTEMI patients presenting with and without hs-cTnT < 5 ng/L. Methods All patients admitted to five centers in Sweden 2011–2015, after the introduction of hs-cTnT, who presented ≤2 h from symptom onset and received a final diagnosis of NSTEMI, were identified through the SWEDEHEART registry. These data and data of hs-cTnT levels were verified in the hospitals' medical records. The registry provided baseline and outcome data. Results Twenty-four (2.6%) of 911 NSTEMI patients presented with hs-cTnT < 5 ng/L. In patients presenting >1–≤2 h from symptom onset the sensitivity for MI when combining hs-cTnT and ECG was 99.4% (95% CI 98.4%–99.8%). In patients presenting ≤1 h, and in patients aged ≤65 years without prior MI, the sensitivity was insufficient. NSTEMI patients presenting with hs-cTnT < 5 ng/L were younger and had less often a prior MI. A total of 62.5 vs. 63.5% of the NSTEMI patients presenting with and without hs-cTnT < 5 ng/L underwent revascularization within 30 days and 4.5 and 3.2% died respectively. Conclusions Hs-cTnT < 5 ng/L at presentation combined with a non-ischemic ECG may be used to rule out MI in patients presenting as early as >1 h from symptom onset with a sufficient sensitivity. Highlights • High-sensitivity troponin T < 5 ng/L combined with a non-ischemic ECG can rule out NSTEMI. • The rule-out algorithm may be used in the second hour from symptom onset. • Younger patients with no prior myocardial infarction should be assessed with caution. • NSTEMI patients with and without T < 5 ng/L have a similar 30-day outcome. [ABSTRACT FROM AUTHOR]

Abstract Background The clinical availability of high-sensitivity cardiac troponin (hs-cTn) has enabled the development of several innovative strategies for the rapid rule-out of acute myocardial infarction (AMI). Due to the lack of direct comparisons, selection of the best strategy for clinical practice is challenging. Methods In a prospective international multicenter diagnostic study enrolling 3696 patients presenting with suspected AMI to the emergency department, we compared the safety and efficacy of 14 different hs-cTn-based strategies: hs-cTn concentrations below the limit of detection (LoD), dual-marker combining hs-cTn with copeptin, ESC 0 h/1 h-algorithm, 0 h/2 h-algorithm, 2 h-ADP-algorithm, NICE-algorithm, and ESC 0 h/3 h-algorithm, each using either hs-cTnT or hs-cTnI. The final diagnosis of AMI was adjudicated by two independent cardiologists using all available clinical information including cardiac imaging and serial hs-cTn concentrations. Results AMI was the final diagnosis in 16% of patients. Using hs-cTnT, safety quantified by the negative predictive value (NPV) and sensitivity was very high (99.8–100% and 99.5–100%) and comparable for all strategies, except the dual-marker approach (NPV 98.7%, sensitivity 96.7%). Similarly, using hs-cTnI, safety quantified by the NPV and sensitivity was very high (99.7–100% and 98.9–100%) and comparable for all strategies, except the dual-marker approach (NPV 96.9%, sensitivity 90.4%) and the NICE-algorithm (NPV 99.1%, sensitivity 94.7%). Efficacy, quantified by the percentage of patients eligible for rule-out, differed markedly, and was lowest for LoD-algorithm (15.7–26.8%). Conclusion All rapid rule-out algorithms, except the dual-marker strategy and the NICE-algorithm using hs-cTnI, favorably combine safety and efficacy, and can be considered for routine clinical practice. Clinical trial registration NCT00470587 , http://clinicaltrials.gov/show/NCT00470587. Highlights • All examined hs-cTn-based rapid rule-out strategies, except for the dual-marker strategy and the NICE-algorithm using hs-cTnI, provide high and comparable safety. • The efficacy of the different hs-cTn-based rapid rule-out strategies varied substantially among the different strategies. • The incidence of 30-day MACE among patients triaged towards rule-out was very low and comparable among the different strategies. • Findings in the subgroup of early presenters overall were similar to those obtained for the whole cohort for the different strategies. • No systematic difference was shown between the rule-out strategies according to the applied hs-cTn assay, except for the NICE algorithm. [ABSTRACT FROM AUTHOR]

Highlights • The study was conducted to examine the effectiveness of a postoperative intervention program in reducing the mortality and improving mobility in hip fracture patients over one year. • A non randomized controlled trial study with follow up of one hundred twenty four admitted hip fracture patients aged 50 years and older to a trauma Unit. The intervention was a postoperative care program in the form of education sessions with an explanatory leaflet on discharge for nutrition and physical exercise program at home. • Follow up phone calls were done at 3 months, 6 months and one year postoperative by one assessor. Physical mobility was assessed by 24 items Western Ontario And McMaster Universities Osteoarthritis Index (WOMAC). • A significant improvement in mobility and reduction of mortality were achieved by the postoperative care program that could be incorporated into the hip fracture patients' care pathway. Abstract Purpose The study was done to investigate whether a postoperative intervention program is effective in reducing mortality and improving mobility in two comparative hip fracture patients over one year postoperatively. Methods A non-randomized controlled trial study with an intervention group of hip fracture patients and historical control group with 12 months follow up. One hundred twenty four admitted hip fracture patients to the Trauma Unit of Assiut University Hospitals, aged 50 years and older were included from 1st July to 31st December 2014. They were divided into 64 and 60 patients as intervention and control groups respectively. Weight, height and bone mineral density were measured and baseline characteristics were taken. The intervention was a postoperative care program in the form of education sessions with an explanatory leaflet on discharge for nutrition and physical exercise program at home. Follow up phone calls were done at 3 months, 6 months and one year postoperatively by one assessor. Physical mobility was assessed by 24 items Western Ontario And McMaster Universities Osteoarthritis Index (WOMAC). Results Mortality was significantly higher in the control group, WOMAC score was significantly better among intervention group through follow up. By multivariate Cox survival analysis, advancing age, no intervention, osteoporosis, postoperative complications, chest infections and heart attacks were significant predictors for mortality. Conclusion A significant improvement in mobility and reduction of mortality was achieved by application of a postoperative care program that could be incorporated into the hip fracture patients' care pathway. [ABSTRACT FROM AUTHOR]

Objective: To explore associations between infertility and metabolic syndrome, and cardiovascular events. Infertility is increasingly a public health issue, with emerging links to chronic disease. Existing literature on infertility focuses primarily on known causes, which likely excludes a substantial number of women for whom there is no known cause or formal diagnosis.Design/setting: We conducted a cross-sectional analysis examining the association between self-reported infertility (i.e., ever experiencing inability to conceive after 12 months of trying to become pregnant) and metabolic syndrome and cardiovascular events (i.e., congestive heart failure, coronary heart disease, heart attack, or stroke). Data were analyzed using multivariate logistic regression.Patient(s): A total of 744 U.S. women, 20-59 years of age, from the National Health and Nutrition Examination Survey (2013-2014), participated in the study. Among them, 15.7% reported ever experiencing infertility, 27.6% met the definition of metabolic syndrome, and 2.84% reported ever having a cardiovascular event.Intervention(s): N/A.Main Outcome Measure(s): Metabolic syndrome and cardiovascular events.Results: Compared to women who had never experienced infertility, women who reported infertility had a 1.79 (95% confidence interval [CI] 1.04, 3.08) higher odds of reporting symptoms of metabolic syndrome and 1.83 (95% CI 1.15, 2.89) times higher odds of having experienced a cardiovascular event. Furthermore, women with self-reported infertility had a 71% higher odds of reporting a cardiovascular event after controlling for metabolic syndrome (95% CI 1.01, 3.00).Conclusions: Our results suggest that among U.S. women, the experience of infertility at any point in a woman's reproductive window may be associated with later-life cardiovascular health. [ABSTRACT FROM AUTHOR]

Background Patients with familial hypercholesterolemia (FH) are at increased risk for premature and subsequent cardiovascular disease. Data on long-term major adverse cardiovascular events (MACE) in patients with FH after percutaneous coronary intervention (PCI) in the era of high-intensity statins are scarce. Objective We assessed the prognostic impact of clinically diagnosed FH on long-term MACE, a composite of all-cause death, myocardial infarction, and ischemic stroke in patients admitted for stable coronary artery disease (SCAD) or acute coronary syndromes (ACSs) undergoing PCI. Methods FH was diagnosed according to the Dutch Lipid Clinic Network diagnosis criteria: "Unlikely FH" diagnosis was defined as 0 to 2 points, "possible FH" as 3 to 5 points, and "probable/definite FH" diagnosis as 6 or higher. Results From a total of 1550 eligible patients (47.4% were admitted for SCAD and 52.6% for ACS), 77 (5.0%) were classified as probable/definite FH, 332 (21.4%) as possible FH, and 1141 (73.6%) as unlikely FH. Mean follow-up was 6.0 ± 2.4 years. After adjustment for possible confounders, patients classified with probable or definite FH (hazard ratio [HR] 1.922 [95% confidence interval (CI) 1.220–2.999]; P =.004), but not patients with possible FH (HR 1.105 [95% CI 0.843–1.447]; P =.470) faced a significant, approximately 2-fold increased risk of MACE compared with patients with unlikely FH. Conclusion After adjustment for confounders, patients with probable or definite FH faced an approximate 2-fold increased risk for long-term MACE compared with patients without FH despite the widespread use of high-intensity statins. The new option of proprotein convertase subtilisin/kexin type 9 gene inhibitors in addition to other current optimal lipid-lowering strategies might help to further improve clinical outcome in patients with probable/definite FH. Highlights • Familial hypercholesterolemia (FH) is a major risk factor for premature and subsequent cardiovascular disease. • Data on long-term major adverse cardiovascular events in patients with FH after coronary stenting are scarce. • 5.0% were classified with probable/definite FH. • Mean follow-up was 6.0 ± 2.4 years. • Probable/definite FH was associated with a 1.9-fold increased risk for MACE. [ABSTRACT FROM AUTHOR]

Abstract Objectives This study introduced and validated a novel flow-independent delayed enhancement technique that shows hyperenhanced myocardium while simultaneously suppressing blood-pool signal. Background The diagnosis and assessment of myocardial infarction (MI) is crucial in determining clinical management and prognosis. Although delayed enhancement cardiac magnetic resonance (DE-CMR) is an in vivo reference standard for imaging MI, an important limitation is poor delineation between hyperenhanced myocardium and bright LV cavity blood-pool, which may cause many infarcts to become invisible. Methods A canine model with pathology as the reference standard was used for validation (n = 22). Patients with MI and normal controls were studied to ascertain clinical performance (n = 31). Results In canines, the flow-independent dark-blood delayed enhancement (FIDDLE) technique was superior to conventional DE-CMR for the detection of MI, with higher sensitivity (96% vs. 85%, respectively; p = 0.002) and accuracy (95% vs. 87%, respectively; p = 0.01) and with similar specificity (92% vs, 92%, respectively; p = 1.0). In infarcts that were identified by both techniques, the entire length of the endocardial border between infarcted myocardium and adjacent blood-pool was visualized in 33% for DE-CMR compared with 100% for FIDDLE. There was better agreement for FIDDLE-measured infarct size than for DE-CMR infarct size (95% limits-of-agreement, 2.1% vs. 5.5%, respectively; p < 0.0001). In patients, findings were similar. FIDDLE demonstrated higher accuracy for diagnosis of MI than DE-CMR (100% [95% confidence interval [CI]: 89% to 100%] vs. 84% [95% CI: 66% to 95%], respectively; p = 0.03). Conclusions The study introduced and validated a novel CMR technique that improves the discrimination of the border between infarcted myocardium and adjacent blood-pool. This dark-blood technique provides diagnostic performance that is superior to that of the current in vivo reference standard for the imaging diagnosis of MI. Graphical abstract [ABSTRACT FROM AUTHOR]

Abstract Aims Milk thistle (Silybum marianum ; SM) is an herb commonly used for hepatoprotection with antioxidant and antifibrotic properties. We investigated in pigs the cardiac effects of SM intake during the acute phase of myocardial infarction (MI) and remodeling period post-MI. Methods Study-1 tested the effect of SM use on the acute phase of MI. Hence, animals were distributed to a control group or to receive SM prior infarction (1.5 h ischemia). Animals were sacrificed after 2.5 h of reperfusion. Study-2 tested the effect of SM use in the cardiac remodeling phase. Accordingly, animals received for 10 d diet ± SM prior MI and followed the same regime for 3 weeks and then sacrificed. Study-3 tested the effect of SM in a non-infarcted heart; therefore, animals received for 10 d diet ± SM and then sacrificed. Results Animals taking SM before MI showed a reduction in cardiac damage (decreased oxidative damage, ROS production and xanthine oxidase levels; preserved mitochondrial function; and increased myocardial salvage; p < 0.05) versus controls. Animals that remained on chronic SM intake post-MI improved left ventricular remodeling. This was associated with the attenuation of the TGFß 1 /TßRs/SMAD2/3 signaling, lower myofibroblast transdifferentiation and collagen content in the border zone (p < 0.05 vs. all other groups). Cardiac contractility improved in animals taking SM (p < 0.05 vs. post-MI-control). No changes in cardiac function or fibrosis were detected in animals on SM but without MI. Conclusion Intake of SM protects the heart against the deleterious effects of an MI and favors cardiac healing. These benefits may be attributed to the antioxidant and antifibrotic properties of SM. Highlights • Medicinal herbs are sold without prescription and understanding of their possible cardiac effects. • Administration of the medicinal herb Milk thistle (Silybum marianum;) prior an MI event increases myocardial salvage in pigs. • Maintenance of chronic intake of Silybum marianum post-MI ameliorates cardiac healing and function. • The influence of Silybum marianum on oxidative damage and the myocardial TGFβ 1 /TβRs/Smad2/3 axis is proposed. [ABSTRACT FROM AUTHOR]

Localization of the left ventricle (LV) in echocardiography is important for the diagnosis of cardiovascular diseases. Previous deep learning approaches leverage semantic segmentation models to perform LV or myocardium segmentation and extract important LV parameters from the binary segmentation masks. Although these algorithms yield promising segmentation results, their per-pixel classification characteristic and complex postprocessing process of the binary masks compromise their robustness and speed. In this paper, inspired by the DeepSnake algorithm in the computer vision community, we develop a deep learning model called LVSnake for left ventricle localization. Our model generates the initial contour by connecting three key landmarks of the left ventricle output by our model including the start point, the apex point, and the end point of the endocardium. Then, a contour adjustment module is designed to refine the initial contour coordinates so as to obtain the final position of the endocardium. The extracted endocardium coordinates are used to perform Myocardial Infarction (MI) detection. Experiment results on the HMC-QU dataset indicate that our model performs more favorably against previous approaches in terms of localization accuracy and robustness. The overall Endpoint-Error (EPE) of our model reaches 3.4 pixels. Using ventricular endocardium location extracted by our method to perform MI detection, the classification accuracy reaches 83.1% which exceeds that of existing studies (79.2%). Our proposed LVSnake can robustly and accurately extract LV positions from echocardiography, which can be used for MI detection. • We proposed the LVSnake model which directly outputs the LV contour. • Our model achieves accurate and robust performance on the LV localization task. • We labeled the LV contour of an MI detection dataset which will be released. • The MI detection's accuracy has improved using the LV contour extracted by our model. [ABSTRACT FROM AUTHOR]

Abstract In the past, exosomes have been thought of as cellular dust. Today, they are thought to be carriers of real biomarkers and intercellular biological information. The composition of exosomes differs according to their source, and the subsequent information they carry, such as protein, microRNA or mRNA, may also be different. Recent studies have demonstrated that exosomes in ischemic diseases can help to make an early diagnosis, and in cellular experiments and animal models, exosomes promote angiogenesis, restrain cell apoptosis and reduce inflammation, among other actions, to protect ischemic organs. There is evidence that these protective effects are related to microRNAs in exosomes. In this review, we discuss the use of exosomes for early diagnosis of ischemic diseases and recent advances in the therapeutic use of exosomes in cell and mammalian models of ischemic diseases. [ABSTRACT FROM AUTHOR]

Background Symptom presentation has been sparsely studied from a gender perspective restricting the inclusion to ST elevation myocardial infarction (STEMI) patients. Correct symptom recognition is vital in order to promptly seek care in STEMI where fast reperfusion therapy is of utmost importance. Female gender has been found associated with atypical presentation in studies on mixed MI populations but it is unclear whether this is valid also in STEMI. Objectives We assessed whether there are gender differences in symptoms and interpretation of these in STEMI, and if this is attributable to sociodemographic and clinical factors. Methods SymTime was a multicenter observational study including a validated questionnaire and data from medical records. Eligible STEMI patients (n = 532) were enrolled within 24 h after admittance at five Swedish hospitals. Results Women were older, more often single and had lower educational level. Chest pain was less prevalent in women (74 vs 93%, p < 0.001), whereas shoulder (33 vs 15%, p < 0.001), throat/neck (34 vs 18%, p < 0.001), back pain (29 versus 12%, p < 0.001) and nausea (49 vs 29%, p < 0.001) were more prevalent. Women less often interpreted their symptoms as of cardiac origin (60 vs 69%, p = 0.04). Female gender was the strongest independent predictor of non-chest pain presentation, odds ratio 5.29, 95% confidence interval 2.85–9.80. Conclusions A striking gender difference in STEMI symptoms was found. As women significantly misinterpreted their symptoms more often, it is vital when informing about MI to the society or to high risk individuals, to highlight also other symptoms than just chest pain. [ABSTRACT FROM AUTHOR]

Background: Simvastatin plus ezetimibe reduced the risk of cardiovascular events in the IMProved Reduction of Outcomes: Vytorin Efficacy International (IMPROVE-IT) study. The aim of this study is to investigate the cost-effectiveness of adding ezetimibe to simvastatin treatment for patients with ACS based on the recently completed IMPROVE-IT trial.Methods: We constructed a Markov state-transition model to evaluate the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness (ICER) associated with co-therapy compared with simvastatin alone from a health care perspective. We ran separate base-case analyses assuming a trial-length and longer term follow-up. One-way sensitivity analyses were used to explore uncertainty in model parameters.Results: In the trial-length model, the ICERs compared with simvastatin alone were $114,400 per QALY for the combination therapy. In 5- and 10-year time horizons, the ICERs remained above the cost-effectiveness threshold of $50,000 per QALY. In the lifetime horizon model, The ICER was $45,046 per QALY for combination treatment compared with simvastatin alone. The combination therapy is cost-effective at an 80% decrease in the current branded simvastatin and ezetimibe cost. Probabilistic sensitivity analysis suggested simvastatin and ezetimibe co-therapy would be a cost-effective alternative to simvastatin monotherapy 60.7% of the time.Conclusions: In our trial-length, 5-year, and 10-year models, the co-therapy was not a cost-effective alternative; however, as follow-up was extended to lifetime, the co-therapy became a cost-effective treatment compared with the simvastatin monotherapy in patients with histories of ACS. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of brief hypoxia (<7 min) due to cardiac arrest on the integrity of the brain and performance on memory and executive functions tasks.Methods: Patients after out-of-hospital cardiac arrest (CA) (n = 9), who were deemed neurologically intact on discharge, were compared to matched patients with myocardial infarction (MI) (n = 9). A battery of clinical and experimental memory and executive functions neuropsychological tests were administered and MRI scans for all patients were collected. Measures of subcortical and cortical volumes and cortical thickness were obtained using FreeSurfer. Manual segmentations of the hippocampus were also performed. APACHE-II scores were calculated based on metrics collected at admission to ICCU for all patients.Results: Significant differences between the two groups were observed on several verbal memory tests. Both hippocampi were significantly reduced (p < 0.05) in the CA patients, relative to MI patients. Hippocampal subfields segmentation showed significantly reduced presubiculum volumes bilaterally. CA patients had on average 10% reduction in volumes bilaterally across hippocampal subfields. No cortical thickness differences survived correction. Significant correlations were observed in the CA group only between the hippocampal volumes and performance on verbal memory tasks, including recollection. Hippocampal volumes and several memory measures (but not other cognitive domains) were strongly correlated with APACHE-II scores on admission in the CA group, but not in the MI group CONCLUSIONS: Chronic patients with cardiac arrest who were discharged from hospital in "good neurological condition" showed an average of 10% reduction in hippocampal volume bilaterally and significant verbal memory deficits relative to matched controls with myocardial infarction, suggesting even brief hypoxic periods suffice to lead to specific hippocampal damage. [ABSTRACT FROM AUTHOR]

Background Heart failure is a serious event in patients with transposition of the great arteries (D-TGA) after atrial redirection surgery. We aimed to determine the association between myocardial fibrosis and systolic and diastolic systemic right ventricle (sRV) dysfunction. Methods Diastolic and systolic function of sRV was prospectively assessed using echocardiography and cardiac magnetic resonance imaging (CMR) in 48 patients with atrially switched D-TGA and 26 healthy subjects. Diastolic function of the subaortic ventricle was assessed by echocardiography Doppler and DTI. In CMR, ejection fraction of sRV and wall stress defined as the product of the systolic blood pressure and volume/mass ratio were assessed. Fibrosis extent within sRV myocardium was evaluated using gadolinium-enhanced magnetic resonance and serum collagen turnover biomarkers. Results Late gadolinium enhancement (LGE) was found in 35% of D-TGA patients, and the collagen degradation biomarker pro-MMP1:TIMP1 ratio was significantly increased in D-TGA patients compared to healthy subjects (1.0 × 10 −2 vs. 2.5 × 10 −2 , p  = 0.04). Increase in sRV wall stress was significantly associated with LGE ( p  = 0.01) and pro-MMP1:TIMP1 ratio ( r  = 0.77, p  < 0.01). After adjustment for age, sex, BMI, blood pressure and cardiac treatment, pro-MMP1:TIMP1 ratio was the strongest determinant of sRVEF (R 2  = 0.85, p  < 0.01). Pro-MMP1:TIMP1 ratio was also significantly correlated with the early diastolic filling parameter E/E′ ( r  = 0.53, p  = 0.02), but this was not anymore the case after adjustment. Conclusions Diastolic and systolic sRV dysfunction is related to myocardial collagen degradation and fibrosis. Research in medical therapies that reduce systemic sRV afterload and limit collagen degradation is warranted in this setting. [ABSTRACT FROM AUTHOR]

Background Lipoprotein(a) [Lp(a)] is a genetic risk factor for cardiovascular disease (CVD), and proinflammatory interleukin-1 (IL-1) genotypes may influence Lp(a)-mediated CVD events. The genotype IL-1(+) is associated with higher rates of inflammation than IL-1(−) genotype. Targeting IL-1β was recently shown to decrease CVD events independent of low-density lipoprotein-cholesterol levels. Objective The objective of the study is to assess the modulatory effect of IL-1 genotypes on risk mediated by Lp(a) Methods We assessed whether IL-1 genotypes modulate the effect of Lp(a) on major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke/transient ischemic attack) and angiographically determined coronary artery disease (CAD). IL-1 genotypes and Lp(a) were measured in 603 patients without diabetes mellitus undergoing angiography. Major adverse cardiovascular events and CAD were assessed over a median of 45 months. Results In multivariable-adjusted analysis, Lp(a) was associated with major adverse cardiovascular events (hazard ratio [HR] [95% confidence interval {CI}]: 2.95 [1.16–7.54], P = .023) and CAD (odds ratio [OR] [95% CI]: 1.84 [1.12–3.03], P = .016) comparing quartile 4 vs quartile 1. In Cox regression analysis, IL-1(+) patients with Lp(a) above the median (>9.2 mg/dL) had a worse event-free cumulative survival (HR [95% CI]: 3.59 [1.07–12.03], P = .039) compared to IL-1(−) patients with Lp(a) below the median. In IL-1(+) patients aged ≤60 years, Lp(a) was also associated with angiographically determined CAD (OR [95% CI]: 2.90 [1.07–7.86], P = .036) comparing quartile 4 vs quartile 1 but not IL-1(−) patients. Conclusion Proinflammatory IL-1(+) genotypes modulate the risk of Lp(a) long-term CVD events and CAD. These data suggest that the dual genetic contributions of elevated Lp(a) levels and IL-1(+) genotypes may identify younger subjects at particularly high risk for CVD events. [ABSTRACT FROM AUTHOR]

Background: Both the modified History, Electrocardiogram, Age, Risk factors and Troponin (HEART) score and the Emergency Department Assessment of Chest pain Score (EDACS) can identify patients with possible acute coronary syndrome (ACS) at low risk (<1%) for major adverse cardiac events (MACE).Objectives: The authors sought to assess the comparative accuracy of the EDACS (original and simplified) and modified HEART risk scores when using cardiac troponin I (cTnI) cutoffs below the 99th percentile, and obtain precise MACE risk estimates.Methods: The authors conducted a retrospective study of adult emergency department (ED) patients evaluated for possible ACS in an integrated health care system between 2013 and 2015. Negative predictive values for MACE (composite of myocardial infarction, cardiogenic shock, cardiac arrest, and all-cause mortality) were determined at 60 days. Reclassification analyses were used to assess the comparative accuracy of risk scores and lower cTnI cutoffs.Results: A total of 118,822 patients with possible ACS were included. The 3 risk scores' accuracies were optimized using the lower limit of cTnI quantitation (<0.02 ng/ml) to define low risk for 60-day MACE, with reclassification yields ranging between 3.4% and 3.9%, while maintaining similar negative predictive values (range 99.49% to 99.55%; p = 0.27). The original EDACS identified the largest proportion of patients as low risk (60.6%; p < 0.0001).Conclusions: Among ED patients with possible ACS, the modified HEART score, original EDACS, and simplified EDACS all predicted a low risk of 60-day MACE with improved accuracy using a cTnI cutoff below the 99th percentile. The original EDACS identified the most low-risk patients, and thus may be the preferred risk score. [ABSTRACT FROM AUTHOR]

Background: It is unclear if isolated postoperative cardiac-troponin elevation, often referred to as myocardial injury, represents a pathological event, as control studies in otherwise healthy adults are lacking.Methods: In this single-centre prospective observational cohort study, serial high-sensitivity cardiac troponin T (hscTnT) plasma concentrations were obtained from young, healthy adults undergoing elective orthopaedic surgery at three time points: before operation, 2-6 h, and 18-30 h after surgery. End points were hscTnT increases after surgery: ≥20% (exceeding analytical variability), ≥50% (exceeding short-term biological variability), and ≥85% (exceeding long-term biological variability). The secondary end point was myocardial injury, defined as new postoperative hscTnT elevation >99th % upper reference limit (URL) (women >10 ng litre-1; men >15 ng litre-1).Results: Amongst the study population (n=95), no hscTnT increase ≥20% was detected in 68 patients (73%). A hscTnT increase between 20% and 49% was observed in 17 patients (18%), 50-84% in seven patients (7%), and ≥85% in three patients (3%). Twenty patients (21%) had an absolute ΔhscTnT between 0 and 2 ng litre-1, 12 patients (13%) between 2 and 4 ng litre-1, three patients between 4 and 6 ng litre-1, and one patient (1%) between 6 and 8 ng litre-1. Myocardial injury (new hscTnT elevation >99th%) was diagnosed in one patient (1%). The median hscTnT concentrations did not increase after operation, and were 4 (3.9-5, inter-quartile range) ng litre-1 at baseline, 4 (3.9-5) ng litre-1 at 2-6 h after surgery, and 4 (3.9-5) ng litre-1 on postoperative day 1.Conclusions: One in four young adult patients without known cardiovascular disease developed a postoperative hscTnT increase, but without exceeding the 99th% URL and without evidence of myocardial ischaemia. These results may have important ramifications for the concept of postoperative myocardial injury, as they suggest that, in some patients, postoperative cardiac-troponin increases may be the result of a normal physiological process in the surgical setting.Clinical Trial Registration: NCT 02394288. [ABSTRACT FROM AUTHOR]

Background We aimed to clarify the impact of metabolic syndrome (MetS) as assessed by different definitions on the cardiovascular mortality in patients with coronary heart disease (CHD). Methods A total of 1692 patients, 6–24 months after myocardial infarction and/or coronary revascularization at baseline, were followed in a prospective cohort study. MetS was identified using four different definitions: standard National Cholesterol Education Program definition (NCEP-ATPIII) based on the presence of ≥ 3 of the following factors: increased waist circumference, raised blood pressure, hypetriglyceridemia, low high-density lipoprotein cholesterol, and increased fasting glycemia; modified NCEP-ATPIII definition (similar, but omitting antihypertensive treatment as an alternative criterion); presence of “atherogenic dyslipidemia”; or “hypertriglyceridemic waist”. The primary outcome was a fatal cardiovascular event at 5 years. Results During 5-year follow-up, 117 patients (6.9%) died from a cardiovascular cause. Patients with MetS by modified NCEP-ATPIII ( n = 1066, 63.0% of the whole sample) had significantly higher 5-year cardiovascular mortality [adjusted hazard risk ratio (HRR) 2.01 [95%CI:1.26–3.22]; p = 0.003] than subjects without MetS. However, when testing single MetS component factors, the majority of attributable mortality risk was driven by increased fasting glycemia (≥ 5.6 mmol/L) [HRR 2.69 (95%CI:1.29–5.62), p = 0.009] and the significance of MetS disappeared. None of the other MetS definitions, i.e., standard NCEP-ATPIII ( n = 1210; 71.5%), “hypertriglyceridemic waist” ( n = 455; 26.9%) or “atherogenic dyslipidemia” ( n = 223; 13.2%) were associated with any significant mortality risk. Conclusions The co-incidence of MetS has a limited mortality impact in CHD patients, while an increase in fasting glycemia seems to be more a specific marker of mortality risk. [ABSTRACT FROM AUTHOR]

Background: Non-invasive cardiac imaging allows detection of cardiac amyloidosis (CA) in patients with aortic stenosis (AS). Our objective was to estimate the prevalence of clinically suspected CA in patients with moderate and severe AS referred for cardiovascular magnetic resonance (CMR) in age and gender categories, and assess associations between AS-CA and all-cause mortality. Methods: We retrospectively identified consecutive AS patients defined by echocardiography referred for further CMR assessment of valvular, myocardial, and aortic disease. CMR identified CA based on typical late-gadolinium enhancement (LGE) patterns, and ancillary clinical evaluation identified suspected CA. Survival analysis with the Log rank test and Cox regression compared associations between CA and mortality. Results: There were 113 patients (median age 74 years, Q1-Q3: 62-82 years), 96 (85%) with severe AS. Suspected CA was present in 9 patients (8%) all >80 years. Among those over the median age of 74 years, the prevalence of CA was 9/57 (16%), and excluding women, the prevalence was 8/25 (32%). Low-flow, low-gradient physiology was very common in CA (7/9 patients or 78%). Over a median follow-up of 18 months, 40 deaths (35%) occurred. Mortality in AS + CA patients was higher than AS alone (56% vs. 20% at 1-year, log rank 15.0, P < 0.0001). Adjusting for aortic valve replacement modeled as a time-dependent covariate, Society of Thoracic Surgery predicted risk of mortality, left ventricular ejection fraction, CA remained associated with all-cause mortality (HR = 2.92, 95% CI = 1.09-7.86, P = 0.03). Conclusions: Suspected CA appears prevalent among older male patients with AS, especially with low flow, low gradient AS, and associates with all-cause mortality. The importance of screening for CA in older AS patients and optimal treatment strategies in those with CA warrant further investigation, especially in the era of transcatheter aortic valve implantation. [ABSTRACT FROM AUTHOR]

Background: Conventional bright blood late gadolinium enhancement (bright blood LGE) imaging is a routine cardiovascular magnetic resonance (CMR) technique offering excellent contrast between areas of LGE and normal myocardium. However, contrast between LGE and blood is frequently poor. Dark blood LGE (DB LGE) employs an inversion recovery T2 preparation to suppress the blood pool, thereby increasing the contrast between the endocardium and blood. The objective of this study is to compare the diagnostic utility of a novel DB phase sensitive inversion recovery (PSIR) LGE CMR sequence to standard bright blood PSIR LGE. Methods: One hundred seventy-two patients referred for clinical CMR were scanned. A full left ventricle short axis stack was performed using both techniques, varying which was performed first in a 1:1 ratio. Two experienced observers analyzed all bright blood LGE and DB LGE stacks, which were randomized and anonymized. A scoring system was devised to quantify the presence and extent of gadolinium enhancement and the confidence with which the diagnosis could be made. Results: A total of 2752 LV segments were analyzed. There was very good inter-observer correlation for quantifying LGE. DB LGE analysis found 41.5% more segments that exhibited hyperenhancement in comparison to bright blood LGE (248/2752 segments (9.0%) positive for LGE with bright blood; 351/2752 segments (12.8%) positive for LGE with DB; p < 0.05). DB LGE also allowed observers to be more confident when diagnosing LGE (bright blood LGE high confidence in 154/248 regions (62.1%); DB LGE in 275/324 (84.9%) regions (p < 0.05)). Eighteen patients with no bright blood LGE were found to have had DB LGE, 15 of whom had no known history of myocardial infarction. Conclusions: DB LGE significantly increases LGE detection compared to standard bright blood LGE. It also increases observer confidence, particularly for subendocardial LGE, which may have important clinical implications. [ABSTRACT FROM AUTHOR]

• The main problem of postmortem diagnosis of Takotsubo syndrome (TTS) is the absence of specific features. • In these cases, acute myocardial infarction is still the main differential diagnosis. • In most of the cases analyzed, macroscopic structural changes were absent. • Our analysis identified recurring but not pathognomonic microscopic features of TTS. • The detection of these histopathological changes may support the post-mortem diagnosis of TTS. Takotsubo syndrome (TTS) is a cardiac syndrome characterized by transient left ventricular systolic dysfunction in the absence of significant obstructive coronary artery disease. At the autopsy, its diagnosis is often challenging, since it is generally thought that it relates to no characteristic macroscopic or microscopic findings. In order to verify this last statement, we performed a systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) criteria. To the best of our knowledge, it is the first systematic review addressing this issue. We identified recurring but not pathognomonic (microscopic) features of TTS: contraction band necrosis and non-specific inflammatory changes (e.g., interstitial infiltrates of mononuclear lymphocytes and macrophages) typically in the absence of microscopic findings typical of acute myocardial infarction. In cases of TTS-related sudden death, careful evaluation of anamnesis, autopsy data and post-mortem genetic results (to exclude other causes) should be considered to overcome the complexity of these cases. [ABSTRACT FROM AUTHOR]

[Display omitted] • Advantages and current applications of nanomedicine-mediated anti-inflammation therapy for atherosclerosis are described. • Recent advances on inflammation-targeted nanomedicines for atherosclerosis diagnosis are summarized. • Challenges and opportunities of inflammation-targeted nanomedicines are highlighted to pave avenues toward personalized medicine for atherosclerosis. Atherosclerosis, formed by fibrofatty lesions in the artery wall, underpins myocardial infarctions, strokes and disabling peripheral artery diseases. Inflammation with multiple maladaptive roles runs through atherosclerotic inception, propagation, and complications. Given degree of inflammation differing among atherosclerotics, inflammation-targeted nanomedicine may produce individualized monitoring and manipulation of inflammatory regulators beyond traditionally slowing down atherosclerosis progression. Equipped with biomimetic membrane, microenvironment-responsive and targeting structures, nanomedicines could escape from the innate immune system and autonomously navigate to targeted lesions, thereby muting inflammation in atherosclerotic sites. Moreover, nanoparticles' advantages go beyond advancing pharmacology. The optimal physicochemical properties of nanoparticles favor noninvasive imaging function to provide diagnostic and prognostic information of atherosclerotic plaques. Despite efficacious ability of the preclinical anti-inflammation nanotherapeutics to reduce atherosclerotic risks, future translation of inflammation-targeted nanomedicines requires to comprehensively refine the strategies that the nanomedicines forestall inflammatory pathways via systemic exposure, drug-cell interactions, and endothelial barrier reconstruction. In this review, we outline the development of diverse nanomedicines to specifically identify pathophysiological changes and combat advanced atherosclerosis along with dynamically tracing inflammatory markers. Finally, challenges and opportunities of inflammation-targeted nanomedicines are highlighted to pave avenues toward personalized medicine for atherosclerosis to stem the growing global burden of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Electrocardiogram (ECG) is a non-invasive and economical diagnostic tool for detecting myocardial infarction (MI). The occurrence of a heart attack causes distortions in the ECG waves. This article extracts morphological features from ECG signals to detect and localize MI. After preprocessing the ECG signal, its fiducial points are identified. Then morphological features such as the amplitude, interval, and angle between waves are extracted. A random forest classifier with 100 trees has been used for classification and feature selection. The method was evaluated using the PTB dataset, containing 52 healthy and 148 MI subjects. We tried to diagnose and localize MI in two schemes: interpatient and intrapatient. In this method, we obtained superior results with an accuracy of 80.98%, a sensitivity of 80.98%, a specificity of 96.32%, a positive predictive value of 79.72%, and an F-score of 79.53% for MI localization in the interpatient scheme compared to the state-of-the-art. Our model achieves an accuracy of 96.54%, a sensitivity of 99.74%, a positive predictive value of 96.09%, and an F-score of 97.88% in the interpatient scheme detection. In the interpatient domain, 96.68% accuracy was obtained using only 6 chest leads for detection. The proposed method is interpretable with low computational complexity and applies a new package of morphological features. Compared to recent studies, in this study, the results have been improved in the interpatient scheme which has more vital clinical significance. • The proposed method applies a new package of morphological features for MI detection. • This method has interpretability based on the clinician's diagnostic strategy. • This algorithm has more vital clinical significance based on the interpatient scheme. • The method has achieved superior results in MI localization of interpatient scheme. [ABSTRACT FROM AUTHOR]