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In this review, recent key publications related to acute coronary syndrome (ACS) are summarized and placed into context of contemporary practice. Landmark trials examining vascular access in ST-elevation myocardial infarction, the management of multivessel disease, acute myocardial infarction and cardiac arrest are discussed. An update in pharmacology for ACS provides updates in major trials relating to P2Y12 inhibitor initiation, deescalation, and use in special populations. Additional updates in the use of lipid-lowering agents and adjunctive medications in ACS are reviewed. Finally, cardiac pathology related to coronavirus disease 2019 (COVID-19), as well as the impact of the COVID-19 global pandemic on the care of patients with ACS, is summarized.

Although chest pain is the most common presenting symptom for both men and women who ultimately receive diagnoses of acute coronary syndrome, there in are important differences in coronary artery disease pathophysiology that can affect patient care. Using a case-based approach, we provide insight into these and other important considerations that every clinician should think of when treating women with chest pain. (Level of Difficulty: Intermediate.), Central Illustration

Visual Abstract, Highlights • Our study supports the feasibility of measuring thrombogenicity in patients with acute myocardial infarction, with intent to predict periprocedural and long-term clinical events, in real-world clinical practice. • Preprocedural assessment of ex vivo thrombogenicity (eg, platelet-fibrin clot strength by thromboelastography) was significantly associated with the risk of coronary microvascular dysfunction. • A combined risk stratification with coronary microvascular dysfunction and platelet-fibrin clot strength increased the prognostic implication to predict the rates of long-term clinical outcomes., Summary The association between thrombogenicity and coronary microvascular dysfunction (CMD) has been poorly explored in patients with acute myocardial infarction (AMI). In our real-world clinical practice (N = 116), thrombogenicity was evaluated with thromboelastography and conventional hemostatic measures, and CMD was defined as index of microcirculatory resistance of >40 U using the invasive physiologic test. High platelet-fibrin clot strength (P-FCS) (≥68 mm) significantly increased the risk of postprocedural CMD (odds ratio: 4.35; 95% CI: 1.74-10.89). Patients with both CMD and high P-FCS had a higher rate of ischemic events compared to non-CMD subjects with low P-FCS (odds ratio: 5.58; 95% CI: 1.31-23.68). This study showed a close association between heightened thrombogenicity and CMD and their prognostic implications after reperfusion in acute myocardial infarction patients.

Hyperprolactinemia is a risk factor for thrombus formation. We present a rare case of a mobile ascending aorta thrombus leading to acute myocardial infarction and cerebral infarction in a patient with idiopathic hyperprolactinemia. (Level of Difficulty: Beginner.), Central Illustration

We encountered siblings with familial Majewski osteodysplastic primordial dwarfism type II (MOPD II) with acute myocardial infarction in adolescence and in their early 20s. We successfully performed percutaneous and surgical coronary interventions. From these cases, we were able to better understand coronary artery disease of MOPD II and provide better management. (Level of Difficulty: Intermediate.), Central Illustration

ST-segment elevation is a dreadful finding in the emergency department because it is often associated with myocardial infarction and demands a prompt and definitive treatment. However, the clinical and echocardiographic assessment of a patient with electrocardiographic changes trumps any electrocardiology expert and should always lead to a clinical decision. (Level of Difficulty: Intermediate.), Central Illustration

Introducción y objetivos: A pesar de los avances en el tratamiento del infarto agudo de miocardio (IAM), este sigue presentando un pronóstico desfavorable. Hay poca evidencia acerca de la evolución de los pacientes con IAM y enfermedad coronavírica de 2019 (COVID-19). El objetivo del estudio es describir la presentación clínica, las complicaciones y los factores predictores de mortalidad hospitalaria en pacientes con IAM durante el brote de COVID-19 en España. Métodos: Se realizó un estudio de cohortes, prospectivo y multicéntrico de todos los pacientes consecutivos con IAM en tratamiento invasivo durante el brote de COVID-19 (15 de marzo a 15 de abril de 2020). Se compararon las características clínicas de los pacientes positivos para COVID-19 con las de los negativos, y se evaluó el efecto de la COVID-19 en la mortalidad mediante emparejamiento por puntuación de propensión y regresión logística. Resultados: Se incluyó a 187 pacientes con IAM: 111 con elevación del segmento ST y 76 sin elevación. De ellos, 32 (17%) resultaron positivos para COVID-19. Las puntuaciones GRACE y Killip-Kimball y varios marcadores inflamatorios resultaron significativamente mayores en los pacientes con COVID-19. La mortalidad total y la cardiovascular fueron significativamente mayores en los pacientes con COVID-19: el 25 frente al 3,8% (p 140 (OR = 23,45; IC95%, 2,52-62,51; p = 0,005) y la COVID-19 (OR = 6,61; IC95%, 1,82-24,43; p = 0,02) resultaron factores independientes de mortalidad hospitalaria. Conclusiones: Durante el brote epidémico, la puntuación GRACE elevada y la COVID-19 fueron los factores independientes de mortalidad hospitalaria en los pacientes con IAM.

A 52-year-old man presented with acute onset of chest pain and was found to have an inferolateral ST-segment elevation myocardial infarction and acute mitral regurgitation due to papillary muscle rupture. This case describes a rare, potentially fatal mechanical complication of acute myocardial infarction. (Level of Difficulty: Beginner.), Graphical abstract

Postpartum papillary muscle rupture (PMR) is extremely uncommon and tolerated poorly with limited management options other than emergency surgical intervention. This case demonstrates the challenges of postpartum PMR in a young woman with unrecognized vascular Ehlers-Danlos syndrome and highlights the importance of preconception screening of cardiovascular disease. (Level of Difficulty: Beginner.), Graphical abstract

Papillary muscle rupture (PMR) is a catastrophic complication of acute myocardial infarction (AMI). We report on 3 consecutive patients with AMI cardiogenic shock due to PMR, treated with combined venoarterial extracorporeal membrane oxygenation and Impella-CP axial flow circulatory support as a bridge to definitive surgery. (Level of Difficulty: Intermediate.), Graphical abstract

Mechanical complications of acute myocardial infarction are infrequent in the modern era of primary percutaneous coronary intervention, but they are associated with high mortality rates. Papillary muscle rupture with acute severe mitral regurgitation is one such life-threatening complication that requires early detection and urgent surgical intervention. (Level of Difficulty: Beginner.), Graphical abstract, Mechanical complications of acute myocardial infarction are infrequent in the modern era of primary percutaneous coronary intervention, but they are…

Objective: To assess the effects of weekend admission vs weekday admission on the management and outcomes of acute myocardial infarction (AMI). Methods: Adult ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) hospital admissions were identified using the National (Nationwide) Inpatient Sample (2000-2016). Interhospital transfers were excluded. Timing of coronary angiography (CA) and percutaneous coronary intervention (PCI) relative to the day of admission was identified. Outcomes of interest included in-hospital mortality, receipt of early CA, timing of CA and PCI, resource utilization, and discharge disposition for weekend vs weekday admissions. Results: Of the 9,041,819 AMI admissions, 2,406,876 (26.6%) occurred on weekends. Compared with 2000, in 2016 there was an increase in weekend STEMI (adjusted odds ratio [aOR], 1.12; 95% CI, 1.08-1.16; P

Introduction and objectives Despite advances in treatment, patients with acute myocardial infarction (AMI) still exhibit unfavorable short- and long-term prognoses. In addition, there is scant evidence about the clinical outcomes of patients with AMI and coronavirus disease 2019 (COVID-19). The objective of this study was to describe the clinical presentation, complications, and risk factors for mortality in patients admitted for AMI during the COVID-19 pandemic. Methods This prospective, multicenter, cohort study included all consecutive patients with AMI who underwent coronary angiography in a 30-day period corresponding chronologically with the COVID-19 outbreak (March 15 to April 15, 2020). Clinical presentations and outcomes were compared between COVID-19 and non-COVID-19 patients. The effect of COVID-19 on mortality was assessed by propensity score matching and with a multivariate logistic regression model. Results In total, 187 patients were admitted for AMI, 111 with ST-segment elevation AMI and 76 with non-ST-segment elevation AMI. Of these, 32 (17%) were diagnosed with COVID-19. GRACE score, Killip-Kimball classification, and several inflammatory markers were significantly higher in COVID-19-positive patients. Total and cardiovascular mortality were also significantly higher in COVID-19-positive patients (25% vs 3.8% [P 140 (OR, 23.45; 95%CI, 2.52–62.51; P = .005) and COVID-19 (OR, 6.61; 95%CI, 1.82-24.43; P = .02) were independent predictors of in-hospital death. Conclusions During this pandemic, a high GRACE score and COVID-19 were independent risk factors associated with higher in-hospital mortality.

Background Acute pericarditis is the most common presentation of pericardial diseases. Although generally benign, complications such as constrictive pericarditis, cardiac tamponade, and recurrence can occur. Research Question What are the clinical factors associated with adverse outcomes in acute pericarditis? Study Design and Methods We used an informatics-based search engine to search for International Classification of Diseases codes related to pericardial disease between January 1, 2009 and November 14, 2018 and then extracted clinical information, including only patients meeting the European Society of Cardiology criteria for acute pericarditis. We then evaluated the predictive value of clinical characteristics for adverse outcomes (cardiac tamponade, constrictive pericarditis, failure of therapy, recurrences, or death). Results We identified 240 patients with a first episode of pericarditis (51 [34-62] years, 56% males and 50% white). Pericarditis was determined to be idiopathic in 126 (53%) cases and related to cardiac injury in 79 (33%). During a median follow-up time of 179 (20-450) days, 82 (34%) patients experienced at least one adverse outcome. Subacute presentation was an independent predictor of adverse outcomes. Patients with postcardiac injury pericarditis had a lower incidence in the composite of failure of treatment and recurrence (13% vs 26%; P = .022) compared with patients with idiopathic pericarditis. Troponin I measurements were obtained in 167 patients (70%). Elevated troponin I levels were associated with lower incidence of recurrences (4% vs 17%; P = .024) and of the composite outcome (13% vs 36%; P = .004). Interpretation Acute pericarditis is associated with at least one adverse outcome in 34% of patients. Subacute presentation and idiopathic etiology are associated with higher incidence of adverse outcomes, whereas elevated troponin I levels identify a group with reduced risk of recurrences.

We describe a patient with of acute right ventricular dysfunction secondary to right ventricular isolated Takotsubo syndrome (TTS). The importance of appropriate differential diagnosis for acute right ventricular dysfunction differential diagnosis of acute right ventricular dysfunction and the differences in diagnosis and management of right ventricular TTS and typical left ventricular TTS are highlighted. (Level of Difficulty: Intermediate.), Graphical abstract, This study describes a case of acute right ventricular dysfunction secondary to right ventricular isolated Takotsubo syndrome (TTS). The importance…

Graphical abstract, Highlight • The number of in vivo cholesterol crystals at the culprit plaque is increased in patients with the no-reflow phenomenon. • The number of cholesterol crystals, lipid arch, and ostium lesion are independent predictors for the no-reflow phenomenon after PCI. • The combination of the number of cholesterol crystals and lipid arc can improve the prediction ability for the no-reflow phenomenon., Background The release of lipid-laden plaque material subsequent to ST-segment elevation myocardial infarction (STEMI) may contribute to the no-reflow phenomenon. The aim of this study was to investigate the association between in vivo cholesterol crystals (CCs) detected by optical coherence tomography (OCT) and the no-reflow phenomenon after successful percutaneous coronary intervention (PCI) in patients with acute STEMI. Methods We investigated 182 patients with STEMI. Based on the thrombolysis in myocardial infarction (TIMI) flow grade after PCI, patients were divided into a no-reflow group (n = 31) and a reflow group (n = 151). On OCT, CCs were defined as thin, high-signal intensity regions within a plaque. A multivariable logistic regression analysis was performed to determine predictors for the no-reflow phenomenon. Results The prevalence of CCs was higher in the no-reflow group than the reflow group (no-reflow group, 77% vs. reflow group, 53%; p = 0.012). The multivariable logistic model showed that the CC number, lipid arc and ostial lesions were positive independent predictors of no-reflow. The combination of a lipid arc ≥ 139°and CC number ≥ 12 showed good predictive performance for the no-reflow phenomenon (sensitivity, 48%; specificity, 93%; and accuracy, 86%). Conclusion In vivo CCs at the culprit plaque are associated with the no-reflow phenomenon after PCI in patients with STEMI. The combination of the number of CCs and lipid arc can predict the no-reflow phenomenon after PCI with a high accuracy of 86%.

Electronic health records; Acute coronary syndrome; Drug adherence; Secondary prevention Registros electrónicos de salud; Síndrome coronario agudo; Adherencia a la medicación; Prevención secundaria Registres electrònics de salut; Síndrome coronària aguda; Adherència a la medicació; Prevenció secundària Objective To describe baseline socio-demographic and clinical characteristics and drugs prescribed for secondary prevention after a first episode of ACS and to assess differences between men and women. Setting PHC in Catalonia. Data source: SIDIAP (Information System for Research in Primary Care). Participants Patients who suffered an ACS during 2009–2016 and followed-up in PHC centres of the Catalan Health Institute in Catalonia. Interventions Not applicable. Main measures Socio-demographic and clinical characteristics at baseline: sex, age, socioeconomic index, toxic habits, comorbidities, study drugs (prescribed for cardiovascular secondary prevention: antiplatelets, betablockers, statins, drugs acting on the renin–angiotensin system) and comedications. Results 8071 patients included, 71.3% of them were men and 80.2% had an acute myocardial infarction. Their mean age was 65.3 and women were older than men. The most frequent comorbidities were hypertension, dyslipidaemia and diabetes and they were more common in women. Antiplatelets (91.3%) and statins (85.7%) were the study drugs most prescribed. The uses of all comedications were significantly higher in women, except for nitrates. The combination of four study groups was initially prescribed in 47.7% of patients and combination of beta-blockers, statins and antiplatelets was prescribed in 18.4%. More men than women received all recommended pharmacological groups. Conclusion Women were older, had more comorbidities and received more comedications. Most patients were treated with a combination of four or three study drugs for secondary prevention. Men initiated more drug treatments for secondary prevention and dual antiplatelet therapy than women. Objetivos Describir las características sociodemográficas y clínicas basales, y los fármacos prescritos para la prevención cardiovascular secundaria tras un síndrome coronario agudo (SCA). Analizar si existen diferencias entre varones y mujeres. Emplazamiento Atención primaria (AP) en Cataluña. Fuente de datos: Sistema de Información para el Desarrollo de la Investigación en AP (SIDIAP). Participantes Pacientes que hayan sufrido un primer SCA durante 2009-2016, seguidos en AP del Instituto Catalán de la Salud en Cataluña. Intervenciones No aplica. Mediciones principales Características sociodemográficas y clínicas al inicio: sexo, edad, índice socioeconómico, hábitos tóxicos, comorbilidades, fármacos de estudio (prescritos para prevención secundaria: antiagregantes, betabloqueantes, estatinas, fármacos del sistema renina-angiotensina) y fármacos concomitantes. Resultados Se incluyeron 8.071 pacientes; 71,3% varones y 80,2% habían sufrido infarto. La edad media era de 65,3 años y las mujeres eran mayores que los varones. Las comorbilidades más frecuentes fueron hipertensión, dislipemia y diabetes; más comunes en mujeres. Antiagregantes (91,3%) y estatinas (85,7%) fueron los fármacos más prescritos. El uso de todas las comedicaciones era más frecuente en mujeres, excepto nitratos. La combinación de los 4 grupos farmacológicos de estudio se prescribió al 47,7% de los pacientes incluidos y la combinación de antiagregante, betabloqueante y estatina al 18,4%. Más varones que mujeres recibieron los fármacos recomendados. Conclusiones Las mujeres incluidas eran mayores, con más comorbilidad y mayor uso de comedicaciones. La mayoría de pacientes eran tratados con la combinación de 3 o 4 fármacos para prevención secundaria. Los varones iniciaban más fármacos para prevención secundaria y más terapia antiagregante doble que las mujeres.

Visual Abstract, Highlights • The role of the CLEC4E during myocardial healing after ischemia-reperfusion injury is unknown. • CLEC4E deletion is associated with reduced cardiac injury, inflammation, and left ventricular structural and functional remodeling. • CLEC4E is a promising target to modulate myocardial inflammation and enhance repair after ischemia-reperfusion injury., Summary The bacterial C-type lectin domain family 4 member E (CLEC4E) has an important role in sterile inflammation, but its role in myocardial repair is unknown. Using complementary approaches in porcine, murine, and human samples, we show that CLEC4E expression levels in the myocardium and in blood correlate with the extent of myocardial injury and left ventricular (LV) functional impairment. CLEC4E expression is markedly increased in the vasculature, cardiac myocytes, and infiltrating leukocytes in the ischemic heart. Loss of Clec4e signaling is associated with reduced acute cardiac injury, neutrophil infiltration, and infarct size. Reduced myocardial injury in Clec4e–/– translates into significantly improved LV structural and functional remodeling at 4 weeks’ follow-up. The early transcriptome of LV tissue from Clec4e–/– mice versus wild-type mice reveals significant upregulation of transcripts involved in myocardial metabolism, radical scavenging, angiogenesis, and extracellular matrix organization. Therefore, targeting CLEC4E in the early phase of ischemia-reperfusion injury is a promising therapeutic strategy to modulate myocardial inflammation and enhance repair after ischemia-reperfusion injury.

Highlights • Beyond restoring myocardial perfusion, there is an unmet need to further reduce the size of myocardial infarctions; only 1 therapy is FDA-approved to specifically treat ischemic myocardium as an adjunct to reperfusion therapy. • Here, we present the basic science and clinical studies showing that treatment with supersaturated oxygen following mechanical reperfusion therapy in patients with large anterior myocardial infarctions improves myocardial perfusion and reduces infarct size. • Early clinical studies also show that supersaturated oxygen improves left ventricular function and reduces adverse left ventricular remodeling in patients with large anterior myocardial infarctions., Summary Despite the fact that door-to-balloon times have been greatly reduced, the rates of death and the incidence of heart failure in patients with ST-segment elevation myocardial infarction (MI) have plateaued. There is still an unmet need to further reduce MI size in the reperfusion era. Most adjunctive therapies to enhance myocardial salvage have failed, but some have shown promise. Currently, the only adjunctive therapy in a pivotal trial that has demonstrated reductions in infarct size is localized delivery of supersaturated oxygen (SSO2) therapy. This review provides background on prior infarct size reduction efforts. The authors describe the preclinical data that shows the effectiveness of SSO2 in reducing MI size, improving regional myocardial blood flow and cardiac function, and reducing adverse left ventricular remodeling—presumably by reducing patchy areas of residual ischemia within the reperfused risk zone. Potential mechanisms by which SSO2 is beneficial are described, including the delivery of high levels of dissolved oxygen through plasma to ischemic, but viable, vascular and myocardial cells, thus allowing their survival and function. The authors then describe the SSO2 clinical trials, demonstrating that in patients with anterior ST-segment elevation MI, SSO2 therapy safely and effectively reduces infarct size, improves cardiac function, and reduces adverse left ventricular remodeling., Central Illustration

Highlights • Calcified coronary lesions are frequently in patients with coronary artery disease. • Intravascular lithotripsy was shown to be safe and effective for treating calcified lesions in coronary artery disease. • Data of intravascular lithotripsy in comparison to standard techniques are lacking. • Intravascular lithotripsy showed higher rate of procedural success without differences in rate of MACE after 12 months in comparison to high- pressure NC-Balloon PTCA., Background Data regarding safety, efficacy, and outcome of intravascular lithotripsy (IVL) in comparison to standard techniques are lacking. This study sought to compare IVL with non-compliant high-pressure balloon percutaneous coronary angioplasty (PTCA). Methods and results We performed a retrospective propensity-score-matched study to compare procedural success in 57 consecutive patients who received IVL-guided PCI in calcified coronary lesions with 171 matched patients who were treated with high-pressure PTCA with a non-compliant (NC)-balloon. The mean minimal lumen diameter (MLD) for the IVL group was 1.08 ± 0.51 mm, and the median percent diameter stenosis on quantitative angiography was 70.2% (interquartile range, 60.2–78.6%). MLD in the high-pressure dilatation group was 0.97 ± 0.43 mm, and the median percent diameter stenosis was 71.5% (interquartile range, 58.5–77.0%). IVL-guided PCI reduced median stenosis to 17.5% (interquartile range, 9.3–19.8%) with an acute gain of 0.93 ± 0.7 mm. High-pressure dilatation resulted in a final median stenosis of 19.3% (interquartile range, 13.33–28.5%). Procedural success was significantly higher (82.5% vs. 61.4%; p: 0.0035) in the IVL group. MACE through 12 months occurred in 10.5% of cases in the IVL group and in 11.1% of the high-pressure group (p = 0.22). Angiographic complications (coronary dissection, slow or no reflow, new coronary thrombus formation, abrupt vessel closure) were very low (0.2% vs. 0.12%). Conclusion IVL resulted in a significantly higher rate of procedural success compared to high- pressure NC-balloon dilatation in patients with calcified coronary lesions. The rate of MACE through 12 months was similar to the standard therapy.

A patient with chronic pulmonary artery hypertension and acute dissection of a main and right pulmonary aneurysm (82 mm) presented with acute myocardial infarction and cardiogenic shock secondary to compression of the left main coronary artery. She required emergency pulmonary artery replacement. She ultimately died due to multiorgan failure and sepsis. (Level of Difficulty: Intermediate.), Central Illustration, A patient with chronic pulmonary artery hypertension and acute dissection of a main and right pulmonary aneurysm (82 mm) presented with acute…

Background: The objective is to study the molecular mechanism(s) underlying cardiac troponin I autoantibody (cTnIAAb) binding to cardiomyocyte and resultant myocardial damage/dysfunction. Methods: cTnIAAb was purified from serum of 10 acute myocardial infarction (AMI) patients with left ventricular remodeling. Recombinant human cTnI was used to generate three mouse-derived monoclonal anti-cTnI antibodies (cTnImAb1, cTnImAb2, and cTnImAb3). The target protein in cardiac myocyte membrane bound to cTnImAb and effect of cTnIAAb and cTnImAb on apoptosis and myocardial function were determined. Findings: We revealed that cTnIAAb/cTnImAb1 directly bound to the cardiomyocyte membraneI±-Enolase (ENO1) and triggered cell apoptosis via increased expression of ENO1 and Bax, decreased expression of Bcl2, subsequently activating Caspase8, Caspase 3, phosphatase and tensin homolog (PTEN) while inhibiting Akt activity. This cTnIAAb-ENO1-PTEN-Akt signaling axis contributed to increased myocardial apoptosis, myocardial collagen deposition, and impaired systolic dysfunction. Interpretation: cTnIAAb is not only the independent risk factor of ventricular remodeling after myocardial injury in patients with AMI, but also involved in the process of ventricular remodeling. Funding Statement: This research was supported by the National Natural Science Foundation of China (Grant#: 81260026) and the Doctoral Innovation Fund from Second military Medical University of China. Declaration of Interests: The authors state: "None." Ethics Approval Statement: This study was approved by the Medical Ethics Committee at Changhai Hospital and Changcheng Hospital Affiliated to Nanchang University and patients enrolled provided signed informed consent. The animal protocol was planned in compliance with the animal protection, animal welfare, and ethical principles and was approved by the IACUC of the Second Military Medical University.

Spontaneous coronary artery dissection (SCAD) is an uncommon form of acute coronary syndrome (ACS). With the increasing recognition of this condition…, Spontaneous coronary artery dissection (SCAD) is an uncommon form of acute coronary syndrome (ACS). With the increasing recognition of this condition presenting as ACS in females, clinicians should always remain vigilant for it. This case describes a patient with congenital heart disease presenting with SCAD. (Level of Difficulty: Advanced.), Graphical abstract

Malignant coronary artery disease (CAD) refers to a severe and extensive atherosclerotic process involving multiple coronary arteries in young individuals (aged

Lipoprotein(a) [Lp(a)] is a circulating lipoprotein, and its level is largely determined by variation in the Lp(a) gene (LPA) locus encoding apo(a). Genetic variation in the LPA gene that increases Lp(a) level also increases coronary artery disease (CAD) risk, suggesting that Lp(a) is a causal factor for CAD risk. Lp(a) is the preferential lipoprotein carrier for oxidized phospholipids (OxPL), a proatherogenic and proinflammatory biomarker. Lp(a) adversely affects endothelial function, inflammation, oxidative stress, fibrinolysis, and plaque stability, leading to accelerated atherothrombosis and premature CAD. The INTER-HEART Study has established the usefulness of Lp(a) in assessing the risk of acute myocardial infarction in ethnically diverse populations with South Asians having the highest risk and population attributable risk. The 2018 Cholesterol Clinical Practice Guideline have recognized elevated Lp(a) as an atherosclerotic cardiovascular disease risk enhancer for initiating or intensifying statin therapy. Keywords: Lipoprotein(a), Oxidized phospholipids, Genetic risk factor, Indians, Acute myocardial infarction, Premature coronary artery disease, Cardiovascular disease, Kringles, Isoforms, Mendelian randomization, Single nucleotide polymorphism, Genome-wide association studies, meta-analysis

Background: Morphine is the recommended analgesic in acute myocardial infarction (AMI). This recommendation has come under scrutiny because of possible slow uptake of oral antiplatelet agents. Objective: We performed a meta-analysis of all available studies in AMI patients treated with prasugrel or ticagrelor (P2Y12 inhibitors) that reported use of morphine prior to loading the antiplatelet agents to critically assess the safety of co-administration of morphine and the newer P2Y12 inhibitors. Methods: Several sources were searched from inception to December 2017 with inclusion of eight studies, largely observational. Mean difference (MD) was calculated for continuous variables, and standardized mean difference (SMD) for platelet function was assessed by the various platelet assays, 2 h after the loading dose of oral P2Y12 inhibitors. Results: Higher platelet activity was noted among morphine group [SMD = 0.8, 95% confidence interval (CI) = 0.4–1.1, p

This paper describes the case of a 68-year-old man who presented in cardiac tamponade due to a right ventricular free wall rupture after a recent ST-segment elevation myocardial infarction. After a pericardiocentesis, the ventricular defect resolved spontaneously. The patient was managed medically and avoided surgical intervention. (Level of Difficulty: Intermediate.), Central Illustration

Highlights • Acute coronary occlusions without ST elevation criteria suffer double mortality without reperfusion. • ECG findings other than ST elevation criteria can identify occlusion myocardial infarction sooner and more accurately. • Our results justify further research to evaluate the external validity of advanced ECG interpretation., Objective In the STEMI paradigm of Acute Myocardial Infarction (AMI), many NSTEMI patients have unrecognized acute coronary occlusion MI (OMI), may not receive emergent reperfusion, and have higher mortality than NSTEMI patients without occlusion. We have proposed a new OMI vs. Non-Occlusion MI (NOMI) paradigm shift. We sought to compare the diagnostic accuracy of OMI ECG findings vs. formal STEMI criteria for the diagnosis of OMI. We hypothesized that blinded interpretation for predefined OMI ECG findings would be more accurate than STEMI criteria for the diagnosis of OMI. Methods We performed a retrospective case-control study of patients with suspected acute coronary syndrome. The primary definition of OMI was either 1) acute TIMI 0–2 flow culprit or 2) TIMI 3 flow culprit with peak troponin T ≥1.0 ng/mL or I ≥10.0 ng/mL. Results 808 patients were included, of whom 49% had AMI (33% OMI; 16% NOMI). Sensitivity, specificity, and accuracy of STEMI criteria vs Interpreter 1 using OMI ECG findings among 808 patients were 41% vs 86%, 94% vs 91%, and 77% vs 89%, and for Interpreter 2 among 250 patients were 36% vs 80%, 91% vs 92%, and 76% vs 89%. STEMI(−) OMI patients had similar infarct size and mortality as STEMI(+) OMI patients, but greater delays to angiography. Conclusions Blinded interpretation using predefined OMI ECG findings was superior to STEMI criteria for the ECG diagnosis of Occlusion MI. These data support further investigation into the OMI vs. NOMI paradigm and suggest that STEMI(−) OMI patients could be identified rapidly and noninvasively for emergent reperfusion using more accurate ECG interpretation.

Purpose of review: Although the respiratory system is the main target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is evident from recent data that other systems, especially cardiovascular and hematological, are also significantly affected. In fact, in severe form, COVID-19 causes a systemic illness with widespread inflammation and cytokine flood, resulting in severe cardiovascular injury. Therefore, we reviewed cardiac injury biomarkers' role in various cardiovascular complications of COVID 19 in recent studies. Recent findings: Cardiac injury biomarkers were elevated in most of the complicated cases of COVID-19, and their elevation is directly proportional to the worst outcome. Evaluation of cardiac biomarkers with markers of other organ damage gives a more reliable tool for case fatalities and future outcome. Summary: Significant association of cardiac biomarkers in COVID-19 cases helps disease management and prognosis, especially in severely ill patients.

Background Urgent recognition and treatment are needed in patients with acute coronary syndrome (ACS), however this may be difficult during the Coronavirus disease 2019 (COVID-19) pandemic with a national lock-down. We aimed to examine the incidence of ACS after national lock-down. Methods The Danish government announced national lock-down on March 11, 2020 and first phase of reopening was announced on April 6. Using Danish nationwide registries, we identified first-time ACS admissions in (1) January 1 to May 7, 2017-2019, and (2) January 1, 2020 to May 6, 2020. Incidence rates of ACS admissions per week for the 2017 to 2019 period and the 2020 period were computed and incidence rate ratios (IRR) were computed using Poisson regression analysis. Results The number of ACS admissions were 8,204 (34.6% female, median age 68.3 years) and 2,577 (34.0% female, median age 68.5 years) for the 2017 to 2019- and 2020 period, respectively. No significant differences in IRRs were identified for weeks 1 to 9 (January 1 to March 4) for 2020 compared with week 1 to 9 for 2017 to 2019. In 2020, significant lower IRRs were identified for week 10 (March 5 to 11) IRR = 0.71 (95% confidence intervals [CI]: 0.58 to 0.87), week 11 (12 to 18 March) IRR = 0.68 (0.56 to 0.84), and week 14 (April 2 to April 8) IRR = 0.79 (0.65 to 0.97). No significant differences in IRRs were identified for week 15 to 18 (April 9 to May 6). In subgroup analysis, we identified that the main result was driven by male patients, and patients ≥60 years. Conclusions During the COVID-19 pandemic with an established national lock-down we identified a significant decline around 30% in the incidence of ACS admissions. Along with the reopening of society, ACS admissions were stabilized at levels equal to previous years.

Background and aims Few studies have reported on the use of continuous glucose monitoring (CGM) during the Covid-19 pandemic. We aimed to examine glycemic control metrics using flash glucose monitoring during insulin treatment and the clinical outcome in hospitalized patients with COVID-19. Methods Prospective, single-center cohort of adult patients diagnosed with type 2 diabetes or hyperglycemia and COVID-19 infection treated with basal bolus insulin regimen. Glycemic control was assessed with the use of intermittent Freestyle Libre flash glucose monitoring during the hospital stay. Outcome of interest were time in range [TIR], time above [TAR] and below [TBR] range, glycemic variability [coefficient of variation [% CV]), and differences in a composite of complications including ICU admission, acute respiratory distress syndrome (ARDS) and acute kidney injury. Results A total of 60 patients were included (44 known diabetes and 16 new onset hyperglycemia). In total 190,080 data points of CGM were available, of which 72.5% of values were within the target area [TIR (70–180 mg/dL)], 22% TAR (>180 mg/dL), and 3% were TBR (180 mg/dl had higher rates of a composite of complications (22.5% vs 16%, p = 0.04). Conclusions Basal bolus insulin regimen was safe and effective in achieving inpatient glycemic control in most patients with COVID-19. The association between TAR and complications indicates the need for improved inpatient glycemic control in hospitalized patients with COVID-19.

Background COVID-19 pandemic has affected around 20million patients worldwide and 2.0 million cases from India. The lockdown was employed to delay the pandemic. However, it had an unintentional impact on acute cardiovascular care, especially acute myocardial infarction (AMI). Observational studies have shown a decrease in hospital admissions for AMI in several developed countries during the pandemic period. We aimed to evaluate the impact of COVID-19 on the AMI admissions patterns across India. Methods In this multicentric, retrospective, cross-sectional study, we included all AMI cases admitted to participating hospitals during the study period 15th March to 15th June 2020 and compared them using a historical control of all cases of AMI admitted during the corresponding period in the year 2019. Major objective of the study is to analyze the changes inthe number of hospital admissions for AMI in hospitals across India. In addition, we intend to evaluate the impact of COVID-19 on the weekly AMI admission rates, and other performance measures like rates of thrombolysis/primary percutaneous interventions (PCI), window period, door to balloon time, and door to needle time. Other objectives include evaluation of changes in the major complications and mortality rates of AMI and its predictors during COVID-19 pandemic. Conclusions This CSI-AMI study will provide scientific evidence about the impact of COVID-19 on AMI care in India. Based on this study, we may be able to suggest appropriate changes to the existing MI guidelines and to educate the public regarding emergency care for AMI during COVID-19 pandemic.

Highlights • Principal component analysis (PCA) can create scores from collinear markers. • This study shows a PCA-derived score can combine cytokines in AMI patients. • An IL-6-IL-8 score using PCA independently predicts poor outcomes in AMI., Introduction Many studies have shown that elevated biomarkers of inflammation following acute myocardial infarction (AMI) are associated with major adverse cardiovascular events (MACE). However, the optimal way of measuring the complex inflammatory response following AMI has not been determined. In this study we explore the use of principal component analysis (PCA) utilising multiple inflammatory cytokines to generate a combined cytokine score that may be predictive of MACE post-AMI. Methods Thirteen inflammatory cytokines were measured in plasma of 317 AMI patients, drawn 48–72 h following symptom onset. Patients were followed-up for one year to determine the incidence of MACE. PCA was used to generate a combined score using six cytokines that were detectable in the majority of patients (IL-1β, -6, -8, and -10; MCP-1; and RANTES), and using a subset of cytokines that were associated with MACE on univariate analysis. Multivariate models using baseline characteristics, elevated individual cytokines and PCA-derived scores determined independent predictors of MACE. Results IL-6 and IL-8 were significantly associated with MACE on univariate analysis and were combined using PCA into an IL-6-IL-8 score. The combined cytokine score and IL-6-IL-8 PCA-derived score were both significantly associated with MACE on univariate analysis. In multivariate models IL-6-IL-8 scores (OR = 2.77, p = 0.007) and IL-6 levels (OR = 2.18, p = 0.035) were found to be independent predictors of MACE. Conclusion An IL-6-IL-8 score derived from PCA was found to independently predict MACE at one year and was a stronger predictor than any individual cytokine, which suggests this may be an appropriate strategy to quantify inflammation post-AMI. Further investigation is required to determine the optimal set of cytokines to measure in this context.

Background Artificial intelligence (AI) promises to provide useful information to clinicians specializing in hypertension. Already, there are some significant AI applications on large validated data sets. Methods and results This review presents the use of AI to predict clinical outcomes in big data i.e. data with high volume, variety, veracity, velocity and value. Four examples are included in this review. In the first example, deep learning and support vector machine (SVM) predicted the occurrence of cardiovascular events with 56%–57% accuracy. In the second example, in a data base of 378,256 patients, a neural network algorithm predicted the occurrence of cardiovascular events during 10 year follow up with sensitivity (68%) and specificity (71%). In the third example, a machine learning algorithm classified 1,504,437 patients on the presence or absence of hypertension with 51% sensitivity, 99% specificity and area under the curve 87%. In example four, wearable biosensors and portable devices were used in assessing a person's risk of developing hypertension using photoplethysmography to separate persons who were at risk of developing hypertension with sensitivity higher than 80% and positive predictive value higher than 90%. The results of the above studies were adjusted for demographics and the traditional risk factors for atherosclerotic disease. Conclusion These examples describe the use of artificial intelligence methods in the field of hypertension.

Visual Abstract, Highlights • SARP of coronary veins alone or in combination with focal MH-SARP provided cardioprotection following occlusion of the left anterior descending artery. • Significant reduction in infarct size was achieved with MH-SARP and SARP with preservation of myocardial function and cell integrity. • MH-SARP or SARP may provide a clinically relevant percutaneous short-term option of cardiac support to high-risk patients undergoing percutaneous coronary intervention., Summary Mild hypothermia (MH) and retroperfusion are 2 techniques proposed to reduce infarct size due to myocardial infarction. The authors evaluated the effects of focal MH combined with selective coronary venous autoretroperfusion (SARP) as an acute cardioprotective modality before percutaneous coronary intervention (PCI) in a swine model of left ventricular myocardial infarction. Significant reduction in infarct size with preservation of cardiac function and cardiomyocyte viability were achieved. The authors propose that SARP alone or in combination with MH may provide a clinically relevant percutaneous short-term option of cardiac support to high-risk patients undergoing PCI.

Central Illustration, Highlights • The present review recapitulates relevant findings related to the role of the receptors of the innate immune system (TLRs and NLRs) in the progression of the most prevalent CVDs. • TLRs and NLRs play a key role in the progression of atherosclerosis, acute myocardial infarction or heart failure. • The development of new specific strategies to impair exacerbated TLR and NLR activation in CVDs are strong candidates for therapy and opens a new research field., Summary Cardiovascular diseases (CVDs) are the leading cause of death in the industrialized world. Most CVDs are associated with increased inflammation that arises mainly from innate immune system activation related to cardiac damage. Sustained activation of the innate immune system frequently results in maladaptive inflammatory responses that promote cardiovascular dysfunction and remodeling. Much research has focused on determining whether some mediators of the innate immune system are potential targets for CVD therapy. The innate immune system has specific receptors—termed pattern recognition receptors (PRRs)—that not only recognize pathogen-associated molecular patterns, but also sense danger-associated molecular signals. Activation of PRRs triggers the inflammatory response in different physiological systems, including the cardiovascular system. The classic PRRs, toll-like receptors (TLRs), and the more recently discovered nucleotide-binding oligomerization domain-like receptors (NLRs), have been recently proposed as key partners in the progression of several CVDs (e.g., atherosclerosis and heart failure). The present review discusses the key findings related to the involvement of TLRs and NLRs in the progression of several vascular and cardiac diseases, with a focus on whether some NLR subtypes (nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing receptor 3 and nucleotide-binding oligomerization domain-containing protein 1) can be candidates for the development of new therapeutic strategies for several CVDs.

Background: Depression is a common condition in cardiac patients. We investigated the effect of cardiac rehabilitation on depressive symptoms as detected by Beck depression inventory II score (BDI) in patients who underwent percutaneous coronary intervention (PCI). Methods: In this cohort, 95 patients met our criteria. Patients were then studied in two groups based on their participation in the rehabilitation program to rehabilitation (exposure) and the control (non-exposure) groups. The control group consisted of those who only participated in the introductory session and decided not to continue the program. Finally, demographic and clinical parameters as well as the BDI scores were compared between the study groups. Results: Data of 35 patients who completed rehabilitation program was compared with 60 patients who did not. There was no significant difference between the study groups regarding the demographic and clinical variables, except for a higher frequency of family history for CAD in the control group (p

Chest pain accounts for approximately 6% of Emergency Department (ED) attendances and is the most common reason for emergency hospital admission. For many years, our approach to diagnosis has required patients to stay in hospital for at least 6–12 h to undergo serial biomarker testing. As less than one fifth of the patients undergoing investigation actually has an acute coronary syndrome (ACS), there is tremendous potential to reduce unnecessary hospital admissions.Recent advances in diagnostic technology have improved the efficiency of care pathways. Decision aids such as the Thrombolysis in Myocardial Infarction (TIMI) risk score and the History, Electrocardiogram, Age, Risk factors and Troponin (HEART) score enable rapid ‘rule out’ of ACS within hours of patients arriving in the ED. With high sensitivity cardiac troponin (hs-cTn) assays, approximately one third of patients can have ACS ‘ruled out’ with a single blood test, and up to two thirds could have an acute myocardial infarction ‘ruled out’ with a second sample taken after as little as 1 h.Building on those recent advances, this paper presents an overview of the principles behind the development of the Troponin-only Manchester Acute Coronary Syndromes (T-MACS) decision aid. This clinical prediction model could be used to ‘rule out’ and ‘rule in’ ACS following a single blood test and to calculate the probability of ACS for every patient. The future potential of this approach is then addressed, including practical applications of artificial intelligence, shared decision making, near-patient testing and personalized medicine. Keywords: Acute myocardial infarction, Acute Coronary Syndromes, Diagnosis, Sensitivity and specificity, Troponins, Troponins, high sensitivity, Emergency medicine

Objective: To assess the role of Copeptin in diagnosis of acute myocardial infarction in troponin-blind period. Subjects and methods: This study was conducted on 40 patients who presented to emergency department complaining of chest pain and were highly suspicious to have acute cardiac ischemia, in addition to 10 subjects serving as a healthy control group. Blood samples were collected for determination of CK-MB, cTnI and Copeptin. These were measured twice (in patients’ group); at 3 h and then at 6–9 h from admission time. Results: The first sample revealed a non-significant difference between UA group and AMI group as regards CKMB and troponin, however, high significant difference was found as regards Copeptin (Z = 5.29, P

Background: Hemodynamic support with Impella (Abiomed Inc., Danvers, MA) devices is becoming a more prevalent treatment option for patients with cardiogenic shock (CS) undergoing percutaneous coronary intervention (PCI). There exists only limited published data regarding outcome differences between male and female patients. Therefore, the objective of this paper is to analyze these gender differences between short-term survival and in-hospital outcomes in those undergoing PCI with CS. Methods: Between January 2011 and July 2016, patients undergoing PCI with simultaneous use of Impella were identified. Only patients presenting with CS were included in the analysis. All-cause in-hospital mortality was the primary outcome. Using SAS 9.4 for propensity score matching, additional secondary outcomes were also compared. Results: The primary outcome was comparable between males and females (39.5% vs. 26.3%, p = 0.33) in CS patients. Secondary outcomes were also comparable and included: myocardial infarction, stroke, CS, heart failure, dialysis requirement, bleeding within 72 h, blood transfusion, dysrhythmia, composite of all complications, major adverse cardiac events. Survival at 30 days was equal in both groups. A reduced mortality in males was noted for pre-PCI initiation of Impella. Additionally, both genders who received pre-PCI Impella support, experienced a significant reduction in inotrope use. Conclusions: Despite the small number of cohorts, this study did not reveal any significant differences among gender with the use of percutaneous left ventricular assist devices for PCI in patients with acute myocardial infarction complicated by CS. However, initiation of Impella prior to PCI may be associated with improved mortality and morbidity in both genders. Keywords: Mechanical circulatory device, Cardiogenic shock, High-risk PCI, Gender

Visual Abstract, Highlights • Rad-GTPase is an LTCC component that functions to govern calcium current in the myocardium. • Deletion of Rad increases myocardial contractility secondary to increased trigger calcium entry. • AMI induces heart failure, including reduced calcium homeostasis, but deletion of Rad prevents AMI myocardial calcium alterations. • Rad deletion prevents post-MI scar spread by attenuating the inflammatory response. • Future studies will explore whether Rad deletion is an effective therapeutic direction for providing combined safe, stable inotropic support to the failing heart in concert with protection against inflammatory signaling., Summary The protein Rad interacts with the L-type calcium channel complex to modulate trigger Ca2+ and hence to govern contractility. Reducing Rad levels increases cardiac output. Ablation of Rad also attenuated the inflammatory response following acute myocardial infarction. Future studies to target deletion of Rad in the heart could be conducted to establish a novel treatment paradigm whereby pathologically stressed hearts would be given safe, stable positive inotropic support without arrhythmias and without pathological structural remodeling. Future investigations will also focus on establishing inhibitors of Rad and testing the efficacy of Rad deletion in cardioprotection relative to the time of onset of acute myocardial infarction.

Highlights • AMI as a result of penetrating thoracic trauma is rare, but can occur secondary to an acute thrombus, even in the absence of a direct cardiac injury. • Regardless of the cause of AMI, medical management should follow current guidelines., Introduction Acute myocardial infarction (AMI) as a result of penetrating thoracic trauma (PTT) is rare; however, there have been a few reports of AMI from gunshot wounds. Presentation of case A patient without a history of coronary artery disease (CAD) presented with stab wounds to the left chest and underwent a left anterior thoracotomy, left lung wedge resection, negative pericardial window, and negative exploratory laparotomy. Shortly after leaving the operating room (OR) in a stable condition, the patient experienced a STEMI. An acute thrombus in the proximal left anterior descending (LAD) artery was identified. Discussion AMI as a result of trauma, both blunt and penetrating, is extremely rare. There have been more reports of AMI secondary to blunt trauma, but it is much less common to find reports in literature of AMI from PTT. Conclusion AMI as a result of penetrating trauma is rare, but can occur secondary to an acute thrombus, even in the absence of a direct cardiac injury. MI should be a consideration in patients with penetrating trauma to the chest, regardless of the intensity of the trauma. At minimum, a 12-lead electrocardiogram (ECG) and a baseline troponin should be obtained at initial evaluation and post-operatively, if surgically managed. If ECG demonstrates findings concerning for MI, it should be followed with an echocardiogram and/or cardiac angiogram to further help guide management, with an early cardiology consultation.

Papillary muscle rupture is a rare and life-threatening complication of acute myocardial infarction (AMI). We present a unique case of double papillary muscle rupture in a patient with three vessel disease and acute thrombotic occlusion of left circumflex obtuse marginal artery as the culprit lesion. (Level of Difficulty: Beginner.), Graphical abstract, Papillary muscle rupture is a rare and life-threatening complication of acute myocardial infarction (AMI). We present a unique case of double…