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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.

The mechanisms of coronavirus disease-2019 (COVID-19)-related myocardial injury comprise both direct viral invasion and indirect (hypercoagulability and immune-mediated) cellular injuries. Some patients with COVID-19 cardiac involvement have poor clinical outcomes, with preliminary data suggesting long-term structural and functional changes. These include persistent myocardial fibrosis, edema, and intraventricular thrombi with embolic events, while functionally, the left ventricle is enlarged, with a reduced ejection fraction and new-onset arrhythmias reported in a number of patients. Myocarditis post-COVID-19 vaccination is rare but more common among young male patients. Larger studies, including prospective data from biobanks, will be useful in expanding these early findings and determining their validity.

Background: Although cardiac troponin T (cTnT) and troponin I(cTnI) are expressed to similar amount in cardiac tissue, cTnI often reach ten-times higher peak levels compared to cTnT in patients with myocardial necrosis such as in acute myocardial infarction (MI). In contrast, similar levels of cTnT and cTnI are observed in other situations such as stable atrial fibrillation and after strenuous exercise.Objective: Examine cTnT and cTnI levels in relation to COVID-19 disease and MI. Methods: Clinical and laboratory data from the local hospital from an observational cohort study of 27 patients admitted with COVID-19 and 15 patients with myocardial infarction (MI) that were analyzed with paired cTnT and cTnI measurement during hospital care.Results: Levels of cTnI were lower than cTnT in COVID-19 patients (TnI/TnT ratio 0.3, IQR: 0.1-0.6). In contrast, levels of cTnI were 11 times higher compared to cTnT in 15 patients with MI (TnI/TnT ratio 11, IQR: 7-14). The peak cTnI/cTnT ratio among the patients with MI following successful percutaneous intervention were 14 (TnI/ TnT ratio 14, IQR: 12-23). The 5 COVID-19 patient samples collected under possible necrotic events had a cTnI/ cTnT ratio of 5,5 (IQR: 1,9-8,3).Conclusions: In patients with COVID-19, cTnT is often elevated to higher levels than cTnI in sharp contrast to patients with MI, indicating that the release of cardiac troponin has a different cause in COVID-19 patients.

Cardiovascular diseases such as myocardial infarction (MI) are among the major causes of death worldwide. Although intramyocardial injection of hydrogels can effectively enhance the ventricular wall, this approach is limited because of its restriction to the poor vascularization in the infarcted myocardium. Here, we reported a new type of hydrogel composed of alginate (ALG) and hyaluronic acid (HA) with lyophilized platelet-rich fibrin (Ly-PRF) for releasing abundant growth factors to realize their respective functions. The results of in vitro studies demonstrated favorable mechanical property and release ability of ALG-HA with Ly-PRF. When injected into the infarcted myocardium, this composite hydrogel preserved heart function and the Ly-PRF within the hydrogel promoted angiogenesis and increased vascular density in both infarcted and border zone, which rescued the ischemic myocardium. These beneficial effects were also accompanied by macrophage polarization and regulation of myocardial fibrosis. Moreover, the autologous origin of Ly-PRF with ALG-HA hydrogel offers myriad advantages including safety profile, easiness to obtain and cost-effectiveness. Overall, this study demonstrated the versatile therapeutic effects of a novel composite hydrogel ALG-HA with Ly-PRF, which optimizes a promising vascularized substitution strategy for improving cardiac function after MI., Graphical abstract Image 1, Highlights • Alginate (ALG) alone has a limited vascularized ability in vivo. • ALG with 20% hyaluronic acid (HA) could attenuate LV remodeling and promote angiogenesis. • ALG-HA with lyophilized platelet-rich fibrin (Ly-PRF) could make further improvement in angiogenesis. • The Ly-PRF is promising for further clinical application because of autologous source and definite therapeutic effects.

The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS–STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS–STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS–STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases., Graphical abstract The review summarizes the current impact of hyperactivation of the cGAS–STING signaling, with emphasis on the link with cardiovascular and metabolic diseases and the emerged pathway's inhibitors for therapeutic prospects.Image 1

Visual Abstract, Highlights • AAV9 vectors can upregulate Rxfp1 mRNA in murine heart after intravenous injection. • RXFP1 upregulation sensitizes the left ventricle to relaxin-induced inotropy. • RXFP1 overexpression protects heart from ischemia-reperfusion injury., Summary Relaxin is a pleiotropic hormone shown to confer cardioprotection in several preclinical models of cardiac ischemia-reperfusion injury. In the present study, the effects of up-regulating relaxin family peptide receptor 1 (RXFP1) via adeno-associated virus serotype 9 (AAV9) vectors were investigated in a mouse model of myocardial infarction. AAV9-RXFP1 vectors were generated and injected in adult male CD1 mice. Up-regulation of Rxfp1 was confirmed via quantitative polymerase chain reaction, and overexpressing animals showed increased sensitivity to relaxin-induced ventricular inotropic response. Overexpressing animals also demonstrated reduced infarct size and preserved cardiac function 24 hours after ischemia-reperfusion. Up-regulation of RXFP1 via AAV9 vectors has potential therapeutic utility in preventing adverse remodeling after myocardial infarction.

BackgroundThe rapid increase in coronavirus disease 2019 (COVID-19) cases during the subsequent waves in Saudi Arabia and other countries prompted the Saudi Critical Care Society (SCCS) to put together a panel of experts to issue evidence-based recommendations for the management of COVID-19 in the intensive care unit (ICU).MethodsThe SCCS COVID-19 panel included 51 experts with expertise in critical care, respirology, infectious disease, epidemiology, emergency medicine, clinical pharmacy, nursing, respiratory therapy, methodology, and health policy. All members completed an electronic conflict of interest disclosure form. The panel addressed 9 questions that are related to the therapy of COVID-19 in the ICU. We identified relevant systematic reviews and clinical trials, then used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach as well as the evidence-to-decision framework (EtD) to assess the quality of evidence and generate recommendations.ResultsThe SCCS COVID-19 panel issued 12 recommendations on pharmacotherapeutic interventions (immunomodulators, antiviral agents, and anticoagulants) for severe and critical COVID-19, of which 3 were strong recommendations and 9 were weak recommendations. ConclusionThe SCCS COVID-19 panel used the GRADE approach to formulate recommendations on therapy for COVID-19 in the ICU. The EtD framework allows adaptation of these recommendations in different contexts. The SCCS guideline committee will update recommendations as new evidence becomes available.

Objective: To ensure compliance with optimal secondary prevention strategies and document the residual risk of patients following revascularization, we established a postrevascularization clinic for risk-factor optimization at 1 year, with outcomes recorded in a web-based registry. Although coronary revascularization can reduce ischemia, medical treatment of coronary artery disease (CAD) remains the cornerstone of ongoing risk reduction. While standardized referral pathways and protocols for revascularization are prevalent and well studied, post-revascularization care is often less formalized. Patients and Methods: The University of Ottawa Heart Institute is a tertiary-care center providing coronary revascularization services. From 2015 to 2019, data were prospectively recorded in the CAPITAL revascularization registry, and patient-level procedural, clinical, and outcome data are collected in the year following revascularization. Major adverse cardiovascular event (MACE) was defined as death, myocardial infarction, unplanned revascularization, or cerebrovascular accident. Kaplan-Meier curves were generated to evaluate time-to-event data for clinical outcomes by risk-factor management, and comparisons were performed using log-rank tests and reported by hazard ratio (HR) and 95% confidence intervals (CIs). Results: A cohort of 4147 patients completed 1-year follow-up after revascularization procedure that included 3462 undergoing percutaneous coronary intervention (PCI), 589 undergoing coronary artery bypass graft (CABG), and 96 undergoing both PCI and CABG. In the year following revascularization (median follow-up 13.3 months—interquartile range [IQR]: 11.9-16.5) 11% of patients experienced MACE, with female patients being disproportionately at risk. Moreover, 47.7% of patients had ≥2 risk factors (diabetes, dyslipidemia, overweight, active smoker) at the time of follow-up, with 45.0% of patients with diabetes failing to achieve target hemoglobin (Hb) A1c, 54.8% of smokers continuing to smoke, and 27.1% of patients failing to achieve guideline-directed lipid targets. Conclusion: Patients who have undergone revascularization procedures remain at elevated risk for MACE, and inadequately controlled risk factors are prevalent in follow-up. This highlights the need for aggressive secondary prevention strategies and implementation of programs to optimize postrevascularization care.

Cardiovascular disease and cancer are the 2 leading causes of death worldwide. Emerging evidence suggests common mechanisms between cancer and cardiovascular disease, including atrial fibrillation and atherosclerosis. With advances in cancer therapies, screening, and diagnostics, cancer-specific survival and outcomes have improved. This increase in survival has led to the coincidence of cardiovascular disease, including atrial fibrillation and atherosclerosis, as patients with cancer live longer. Additionally, cancer and cardiovascular disease share several risk factors and underlying pathophysiologic mechanisms, including inflammation, cancer-related factors including treatment effects, and alterations in platelet function. Patients with cancer are at increased risk for bleeding and thrombosis compared with the general population. Although optimal antithrombotic therapy, including agent choice and duration, has been extensively studied in the general population, this area remains understudied in patients with cancer despite their altered thrombotic and bleeding risk. Future investigation, including incorporation of cancer-specific characteristics to traditional thrombotic and bleeding risk scores, clinical trials in the cancer population, and the development of novel antithrombotic and anti-inflammatory strategies on the basis of shared pathophysiologic mechanisms, is warranted to improve outcomes in this patient population., Central Illustration, Highlights • Cancer and cardiovascular disease increasingly coexist, and patients with cancer are often undertreated. • Cancer and cardiovascular disease share common pathophysiology, including inflammation. • Thrombosis and bleeding risk scores often underperform in patients with cancer and cardiovascular disease. • Inclusion of cancer status in cardiovascular trials and risk scores may improve cardiovascular outcomes.

Background Studies reported a decrease in hospital admissions for myocardial infarction (MI) in early 2020 as a result of the coronavirus disease 2019 (COVID-19) crisis, mainly restricted to the beginning of the pandemic. Aims To describe national trends in hospital admissions for MI in 2020, and to compare patient characteristics, in-hospital prognosis and 90-day mortality between patients who had an MI in 2020 and those admitted in 2017–2019. Methods All patients hospitalized for MI in France from 2017 to 2020 were selected from the national hospital discharge database. Analyses compared temporal trends in MI admissions, in-hospital cardiac complications and mortality rates in 2020 versus 2017–2019. Results In 2020, 94,747 patients were hospitalized for MI, corresponding to a 6% decrease in MI admissions compared with 2017–19. This decrease was larger during the first lockdown (–24%; P

Right heart failure is a dreaded sequelae of proximal right coronary artery occlusion that can complicate an angiogram or percutaneous coronary intervention. This case illustrates the use of a percutaneous intraluminal microaxial right ventricular assist device for high-risk percutaneous coronary intervention of an ostial right coronary artery dissection in refractory right heart failure. (Level of Difficulty: Advanced.), Central Illustration

Axial-flow ventricular assist devices are being increasingly used to support hemodynamically compromised patients undergoing percutaneous coronary intervention. Periprocedural valvular complications have been recognized in a few case reports. We present a unique case of entanglement of the Impella within he mitral subvalvular apparatus, retrieved successfully using a snare under fluoroscopic guidance. (Level of Difficulty: Advanced.), Central Illustration

Objective The COVID-19 pandemic has forced the cancellation of planned surgery and led to significant surgical service reductions. Early intervention in aortovascular disease is often critical and cannot be deferred despite these reductions. There is urgent need to evaluate the provision and outcomes of thoracic aortovascular intervention during the peak of the pandemic. Methods Prospective data was collected for patients receiving open and endovascular thoracic aortovascular intervention over two-time points; January-May 2020 and January-May 2019 at three tertiary cardiovascular centres. Baseline demographics, cardiovascular risk and COVID-19 screening results were noted. Primary outcomes were median length of intensive care unit and hospital stay, intra-operative mortality, 30-day mortality, post-operative stroke, and spinal cord injury. Results Patients operated in 2020 (41) had significantly higher median EuroSCORE II than 2019 (53) (7.44 vs. 5.86, P = 0.032) and rates of previous cardiac (19.5% vs. 3.8%, P = 0.019), aortic (14.6% vs. 1.9%, P = 0.041), and endovascular (22.0% vs. 3.8%, P = 0.009) intervention. There was an increase in proportion of urgent cases in 2020 (31.7% vs. 18.9%). There were no intra-operative deaths in 2020 and 1 in 2019 (P = 1.00). There were no significant differences (P ≥ 0.05) in 30-day mortality (4.9% vs. 13.2%), median intensive care unit length of stay (72 vs. 70 hr), median hospital length of stay (8 vs. 9 days), post-operative stroke (3 vs. 6), or spinal cord injury (2 vs. 1) between 2020 and 2019 respectively. Conclusions Despite the increased mortality risk of patients and urgency of cases during COVID-19, complicated by the introduction of cohorting and screening regimens, thoracic aortovascular intervention remained safe with comparable in outcomes to pre-COVID-19.

Objective To carry out a systematic review of the effect of cardiac rehabilitation (CR) and its components on cardiovascular outcomes in patients with stable angina. Methods We searched the databases including Ovid MEDLINE, Ovid Embase, Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from their inception up to November 1, 2017. The search was not restricted to time or publication status but was limited to the English language. Two independent investigators screened the identified studies and extracted the data in duplicate. We reviewed the included studies and, where possible, pooled their results and conducted meta-analyses. Risk of bias was assessed using Cochrane Collaboration tools. Results The search identified 7508 studies. Ten randomized trials including 4005 participants with the mean (SD) age of 59.6 (5.7) years were considered eligible for inclusion in our analyses. The results of meta-analyses of exercise-based CR for patients with stable angina revealed that CR improved exercise capacity (the difference between baseline and follow-up was 0.76 watt [0.49 to 1.02] higher in the CR group vs the non-CR group) and decreased angina frequency (standard mean difference, −0.27 [CI, −0.43 to 0.11]). No significant differences were noted in other outcomes, including quality of life. Mortality could not be adequately assessed because it was analyzed in only 1 exercise-based CR study. Conclusion Our systematic review, involving a relatively small number of studies with low to moderate risk of bias and with considerable heterogeneity, found a significant decrease in angina frequency and increase in exercise capacity in patients with stable angina who participated in an exercise-based CR program. Studies involving the impact of components of CR are limited and generally report beneficial outcomes. Additional studies are needed to clarify the possible role of CR in the management of patients with stable angina.

Highlights • Revascularization for PAD has been characterized by the adaptation of technologies from the treatment of CAD, with few therapies specifically developed for PAD. • In light of recent increases in all-cause mortality driven by endovascular PAD interventions that employ elution of antiproliferative agents, this review highlights the unmet need to address underlying local inflammation and proposes an alternative therapeutic approach. • Development of next-generation PAD-specific endovascular interventions will benefit from integration of specialized immunotherapies that target macrophage polarization and focus on vessel healing., Summary Peripheral artery disease (PAD) has a significant impact on human health, affecting 200 million people globally. Advanced PAD severely diminishes quality of life, affecting mobility, and in its most severe form leads to limb amputation and death. Treatment of PAD is among the least effective of all endovascular procedures in terms of long-term efficacy. Chronic inflammation is a key driver of PAD; however, stents and coated balloons eluting antiproliferative drugs are most commonly used. As a result, neither stents nor coated balloons produce durable clinical outcomes in the superficial femoral artery, and both have recently been associated with significantly increased mortality. This review summarizes the most common clinical approaches and limitations to treating PAD and highlights the necessity to address the underlying causes of inflammation, identifying macrophages as a novel therapeutic target in the next generation of endovascular PAD intervention., Central Illustration

Objective: To evaluate the magnitude of the association between risk factors and premature myocardial infarction (MI) (men aged 18-55 years; women aged 18-65 years). Patients and Methods: We searched MEDLINE and other databases from inception through April 30, 2020, as well as bibliography of articles selected for data extraction. We selected observational studies reporting the magnitude of the association of at least 1 risk factor (demographic characteristics, lifestyle factors, clinical risk factors, or biomarkers) with premature MI and a control group. Pooled risk estimates (random effects) from all studies unadjusted and adjusted for risk factors were reported as summary odds ratios (ORs) with 95% CIs. Results: From 35,320 articles of 12.7 million participants, we extracted data on 19 risk factors from 77 studies across 58 countries. Men had a higher risk of premature MI (OR, 2.39; 95% CI, 1.71 to 3.35) than did women. Family history of cardiac disease was associated with a higher risk of premature MI (OR, 2.67; 95% CI, 2.29 to 3.27). Major modifiable risk factors associated with higher risk were current smoking (OR, 4.34; 95% CI, 3.68 to 5.12 vs no/former), diabetes mellitus (OR, 3.54; 95% CI, 2.69 to 4.65), dyslipidemia (OR, 2.94; 95% CI, 1.76 to 4.91), and hypertension (OR, 2.85; 95% CI, 2.48 to 3.27). Higher body mass index carried higher risk (OR, 1.46; 95% CI, 1.24 to 1.71 for ≥25 kg/m2 vs

Visual Abstract, Highlights • A simple, biohybrid patch made of polymer (PECUU) and ECM, without cellular components, was able to induce positive remodeling features when applied over chronic infarcts with severely dilated hearts and high cardiac function impairment in rats. • The remodeling benefit was particularly notable in a subgroup of the sickest rats with very low initial ejection fraction in which the echocardiographic endpoints were found to improve after treatment. • This technological approach may hold promise for future translation to patients in a chronic scenario., Summary A biohybrid patch without cellular components was implanted over large infarcted areas in severely dilated hearts. Nonpatched animals were assigned to control or losartan therapy. Patch-implanted animals responded with better morphological and functional echocardiographic endpoints, which were more evident in a subgroup of animals with very low pre-treatment ejection fraction (

Coronary intraluminal white clot formation, apparently in response to acetylcholine testing, may explain a woman’s long-term history of daily chest pain and multiple myocardial infarctions. Acetylcholine testing reproduced chest pain and revealed luminal filling defects in multiple vessels; imaging showed fresh white platelet clots. Antiplatelet prasugrel has substantially suppressed her symptoms. (Level of Difficulty: Advanced.), Central Illustration

Background Published data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear. Objectives The purpose of this study was to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre–COVID-19 cohorts. Methods From March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry. Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS. Outcomes were in-hospital major cardiovascular events (all-cause mortality, re–myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis). Results were compared with national pre–COVID-19 databases (MINAP [Myocardial Ischaemia National Audit Project] 2019 and BCIS [British Cardiovascular Intervention Society] 2018 to 2019). Results In 144 ST-segment elevation myocardial infarction (STEMI) and 121 non–ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs. BCIS: median 339.0 min vs. 173.0 min; p, Central Illustration

Background The coronavirus disease 2019 (COVID-19) pandemic has impacted many aspects of ST-segment elevation myocardial infarction (STEMI) care, including timely access to primary percutaneous coronary intervention (PPCI). Objectives The goal of the NACMI (North American COVID-19 and STEMI) registry is to describe demographic characteristics, management strategies, and outcomes of COVID-19 patients with STEMI. Methods A prospective, ongoing observational registry was created under the guidance of 3 cardiology societies. STEMI patients with confirmed COVID+ (group 1) or suspected (person under investigation [PUI]) (group 2) COVID-19 infection were included. A group of age- and sex-matched STEMI patients (matched to COVID+ patients in a 2:1 ratio) treated in the pre-COVID era (2015 to 2019) serves as the control group for comparison of treatment strategies and outcomes (group 3). The primary outcome was a composite of in-hospital death, stroke, recurrent myocardial infarction, or repeat unplanned revascularization. Results As of December 6, 2020, 1,185 patients were included in the NACMI registry (230 COVID+ patients, 495 PUIs, and 460 control patients). COVID+ patients were more likely to have minority ethnicity (Hispanic 23%, Black 24%) and had a higher prevalence of diabetes mellitus (46%) (all p, Central Illustration

Hematopoietic stem cell transplantation (HSCT) is a standard treatment for several malignancies, and >50,000 HSCT are performed annually worldwide. As survival after HSCT improves, cardiovascular disease and associated risk factors have gained importance as a significant cause of morbidity and mortality in this cohort. In this article, we detail the risk factors for cardiovascular disease and their impact in patients undergoing HSCT. Additionally, we critically review the data on the impact of physical exercise in patients undergoing HSCT. Although limited by significant heterogeneity in methodologies, small sample sizes, attrition, and lack of long-term cardiovascular follow-up, most of these studies reinforce the beneficial effects of physical activity and exercise in this patient population. Cardiac rehabilitation (CR) is a structured exercise and lifestyle modification program that is typically instituted in patients who experience acute cardiovascular events. We review the data on CR in the oncologic and nononcologic populations with an aim of building a framework for use of CR in HSCT patients., Central Illustration, Highlights • Patients surviving HSCT have a higher incidence of cardiovascular risk factors and cardiovascular disease than the general population. • Physical activity can improve cardiovascular fitness, strength, and quality of life and decrease fatigue in HSCT patients and survivors. • In addition to physical exercise, cardiac rehabilitation also involves dietary and smoking cessation counseling, medication management, and psychosocial support, and it may therefore offer a unique framework to mitigate cardiovascular risk in HSCT. • Early referral, cardiovascular risk stratification, monitoring for complications, and multimodal lifestyle interventions should form the backbone of cardiac rehabilitation in this population. • Outcome data on quality of life indices and survival as potential benefits of cardiac rehabilitation in HSCT are needed.

Visual Abstract, Highlights • Myocardial matrix hydrogel preserves LV volumes and apical wall thickening in a chronic MI model. • Myocardial matrix hydrogel trends toward reduced fibrosis. • In vivo differential gene expression analysis shows the matrix modulates cardiac muscle contraction, metabolism, fibrosis, and the inflammatory/immune response in a chronic MI model., Summary A first-in-man clinical study on a myocardial-derived decellularized extracellular matrix hydrogel suggested the potential for efficacy in chronic myocardial infarction (MI) patients. However, little is understood about the mechanism of action in chronic MI. In this study, the authors investigated the efficacy and mechanism by which the myocardial matrix hydrogel can mitigate negative left ventricular (LV) remodeling in a rat chronic MI model. Assessment of cardiac function via magnetic resonance imaging demonstrated preservation of LV volumes and apical wall thickening. Differential gene expression analyses showed the matrix is able to prevent further negative LV remodeling in the chronic MI model through modulation of the immune response, down-regulation of pathways involved in heart failure progression and fibrosis, and up-regulation of genes important for cardiac muscle contraction.

Background The extent to which co-occurrence of cardiovascular disease (CVD) and cancer is due to shared risk factors or other mechanisms is unknown. Objectives This study investigated the association of standard CVD risk factors, CVD biomarkers, pre-existing CVD, and ideal cardiovascular (CV) health metrics with the development of future cancer. Methods This study prospectively followed Framingham Heart Study and PREVEND (Prevention of Renal and Vascular End-Stage Disease) study participants free of cancer at baseline and ascertained histology-proven cancer. This study assessed the association of baseline CV risk factors, 10-year atherosclerotic (ASCVD) risk score, established CVD biomarkers, prevalent CVD, and the American Heart Association (AHA) Life’s Simple 7 CV health score with incident cancer using multivariable Cox models. Analyses of interim CVD events with incident cancer used time-dependent covariates. Results Among 20,305 participants (mean age 50 ± 14 years; 54% women), 2,548 incident cancer cases occurred over a median follow-up of 15.0 years (quartile 1 to 3: 13.3 to 15.0 years). Traditional CVD risk factors, including age, sex, and smoking status, were independently associated with cancer (p < 0.001 for all). Estimated 10-year ASCVD risk was also associated with future cancer (hazard ratio [HR]: 1.16 per 5% increase in risk; 95% confidence interval [CI] 1.14 to 1.17; p < 0.001). The study found that natriuretic peptides (tertile 3 vs. tertile 1; HR: 1.40; 95% CI: 1.03 to 1.91; p = 0.035) were associated with incident cancer but not high-sensitivity troponin (p = 0.47). Prevalent CVD and the development of interim CV events were not associated with higher risk of subsequent cancer. However, ideal CV health was associated with lower future cancer risk (HR: 0.95 per 1-point increase in the AHA health score; 95% CI: 0.92 to 0.99; p = 0.009). Conclusions CVD risk, as captured by traditional CVD risk factors, 10-year ASCVD risk score, and natriuretic peptide concentrations are associated with increased risk of future cancer. Conversely, a heart healthy lifestyle is associated with a lower risk of future cancer. These data suggest that the association between CVD and future cancer is attributable to shared risk factors., Central Illustration

Background Cardiovascular disease (CVD) can occur in COVID-19 and has impact on clinical course. Data on CVD prevalence in hospitalized COVID-19 patients and sequelae in survivors is limited. Aim of this prospective study carried out on consecutive unselected COVID-19 population, was to assess: 1) CVD occurrence among hospitalized COVID-19 patients, 2) persistence or new onset of CVD at one-month and one-year follow-up. Methods Over 30 days n = 152 COVID-19 patients underwent cardiovascular evaluation. Standard electrocardiogram (ECG), Troponin and echocardiography were integrated by further tests when indicated. Medical history, arterial blood gas, blood tests, chest computed tomography and treatment were recorded. CVD was defined as the occurrence of a new condition during the hospitalization for COVID-19. Survivors attended a one-month follow-up visit and a one-year telephone follow-up. Results Forty-two patients (28%) experienced a wide spectrum of CVD with acute myocarditis being the most frequent. Death occurred in 32 patients (21%) and more frequently in patients who developed CVD (p = 0.032). After adjustment for confounders, CVD was independently associated with death occurrence. At one-month follow-up visit, 7 patients (9%) presented persistent or delayed CVD. At one-year telephone follow-up, 57 patients (48%) reported persistent symptoms. Conclusion Cardiovascular evaluation in COVID-19 patients is crucial since the occurrence of CVD in hospitalized COVID-19 patients is common (28%), requires specific treatment and increases the risk of in-hospital mortality. Persistence or delayed presentation of CVD at 1-month (9%) and persistent symptoms at 1-year follow-up (48%) suggest the need for monitoring COVID-19 survivors., Graphical abstract Unlabelled Image

Fibrosis is a pathological reparative process that can occur in most organs and is responsible for nearly half of deaths in the developed world. Despite considerable research, few therapies have proven effective and been approved clinically for treatment of fibrosis. Artemisinin compounds are best known as antimalarial therapeutics, but they also demonstrate antiparasitic, antibacterial, anticancer, and anti-fibrotic effects. Here we summarize literature describing anti-fibrotic effects of artemisinin compounds in in vivo and in vitro models of tissue fibrosis, and we describe the likely mechanisms by which artemisinin compounds appear to inhibit cellular and tissue processes that lead to fibrosis. To consider alternative routes of administration of artemisinin for treatment of internal organ fibrosis, we also discuss the potential for more direct oral delivery of Artemisia plant material to enhance bioavailability and efficacy of artemisinin compared to administration of purified artemisinin drugs at comparable doses. It is our hope that greater understanding of the broad anti-fibrotic effects of artemisinin drugs will enable and promote their use as therapeutics for treatment of fibrotic diseases., Graphical abstract Artemisinin drugs, isolated from Artemisia, effectively prevent or treat multiple types of tissue fibrosis when administered to several preclinical animal models of varied etiologies.Image 1

Intramyocardial dissection is a rare complication of myocardial infarction, trauma, and percutaneous intervention. It is usually caused by hemorrhagic dissection among the spiral myocardial fibers. We hereby report the case of a patient with left ventricular intramyocardial dissection who presented with acute decompensated heart failure. (Level of Difficulty: Advanced.), Graphical abstract

Visual Abstract, Highlights • Leptin protects against progression to heart failure after myocardial infarction. • This beneficial effect requires activation of the brain melanocortin system. • Stimulation of brain MC4R recapitulates the cardiac protective effects of leptin. • Leptin-MC4R activation improves cardiac substrate oxidation and mitochondrial function. • It also improves Ca2+ coupling and contractile function in viable cardiomyocytes after MI., Summary Heart failure has a high mortality rate, and current therapies offer limited benefits. The authors demonstrate that activation of the central nervous system leptin-melanocortin pathway confers remarkable protection against progressive heart failure following severe myocardial infarction. The beneficial cardiac-protective actions of leptin require activation of brain melanocortin-4 receptors and elicit improvements in cardiac substrate oxidation, cardiomyocyte contractility, Ca2+ coupling, and mitochondrial efficiency. These findings highlight a potentially novel therapeutic approach for myocardial infarction and heart failure.

Background\ud \ud Cardiac magnetic resonance imaging (MRI) is emerging as an important imaging tool in the assessment of heart failure with preserved ejection fraction (HFpEF). This systematic review and meta-analysis aim to synthesise and consolidate the current literature on cardiac MRI for prognostication of HFpEF.\ud \ud \ud Methods design\ud \ud Systematic review and meta-analysis. Data sources: Scopus (PubMed and Embase) for studies published between 2008 and 2019. Eligibility criteria for study selection were studies that evaluated the prognostic role of cardiac MRI in HFpEF. Random effects meta-analyses of the reported hazard ratios (HR) for clinical outcomes was performed.\ud \ud \ud Results\ud \ud Initial screening identified 97 studies. From these, only nine (9%) studies met all the criteria. The main cardiac MRI methods that demonstrated association to prognosis in HFpEF included late gadolinium enhancement (LGE) assessment of scar (n = 3), tissue characterisation with T1-mapping (n = 4), myocardial ischaemia (n = 1) and right ventricular dysfunction (RVSD) (n = 1). The pooled HR for all 9 studies was 1.52 (95% CI 1.05–1.99, P < 0.01). Sub-evaluation by cardiac MRI methods revealed varying HRs: LGE (net n = 402, HR = 1.6, 95% CI 0.42–2.78, P = 0.008); T1-mapping (n = 1623, HR = 1.25, 95% CI 0.891–1.60, P < 0.001); myocardial ischaemia or RVSD (n = 325, HR = 3.19, 95% CI 0.30–6.08, P = 0.03).\ud \ud \ud Conclusion\ud \ud This meta-analysis demonstrates that multiparametric cardiac MRI has value in prognostication of patients with HFpEF. HFpEF patients with a detectable scar on LGE, fibrosis on T1-mapping, myocardial ischaemia or RVSD appear to have a worse prognosis.\ud \ud \ud PROSPERO registration number\ud \ud CRD42020187228.

COVID-19 associated coagulopathy and mortality related to thrombotic complications have been suggested as biological mediators in racial disparities related to COVID-19. We studied the adjusted prevalence of acute ischemic stroke, pulmonary embolism, myocardial infarction, and deep venous thrombosis stratified by race in hospitalized patients in one New York City borough during the local COVID-19 surge. The multi-racial cohort included 4299 patients hospitalized with COVID-19, 9% of whom were white, 40% black, 41% Hispanic and 10% Asian or other. We found a 6.1% prevalence of composite thrombotic events. There were no significant race-specific differences in thrombotic events when adjusting for basic demographics, socioeconomic factors, medical comorbidities or biomarkers using a stepwise regression model. We therefore found no evidence that the racial disparities related to COVID-19, and specifically thrombotic complications, are caused by biological differences in race.

Intramural coronary hematoma (IMCH) is a rare cause of acute myocardial infarction (MI). We aim to review the current knowledge and share our experience with the diagnosis and management of a patient presenting with traumatic IMCH leading to an acute ST-segment elevation MI. (Level of Difficulty: Intermediate.), Graphical abstract

Large intracoronary thrombus has been reported in significant number of patients with STEMI. Primary PCI is the current standard of care in patients of STEMI. Despite the availability of dual antiplatelets, GP IIb/IIIa inhibitor and effective anticoagulation regimens, large intracoronary thrombus remains one of the biggest challenge to interventional cardiologists during primary PCI. Large intracoronary thrombus may lead to distal embolization, no/slow reflow or embolization into a non-culprit vessel and is associated with adverse cardiovascular outcome. There is no ideal management strategy. We hereby discuss the current available methods/strategies to deal with large thrombus burden encountered during primary PCI, in the current manuscript.

Myocardial infarction with nonobstructed coronary arteries (MINOCA) can be triggered by intense emotions. We report 5 cases of emotional stress–related death where forensic examination attributed myocardial infarction to a coronary spasm, with the ultimate cause of death being arrhythmias in 4 cases and cardiac rupture in the fifth. (Level of Difficulty: Beginner.), Graphical abstract, Myocardial infarction with nonobstructed coronary arteries (MINOCA) can be triggered by intense emotions. We report 5 cases of emotional…

The cardiovascular system is affected broadly by severe acute respiratory syndrome coronavirus 2 infection. Both direct viral infection and indirect injury resulting from inflammation, endothelial activation, and microvascular thrombosis occur in the context of coronavirus disease 2019. What determines the extent of cardiovascular injury is the amount of viral inoculum, the magnitude of the host immune response, and the presence of co-morbidities. Myocardial injury occurs in approximately one-quarter of hospitalized patients and is associated with a greater need for mechanical ventilator support and higher hospital mortality. The central pathophysiology underlying cardiovascular injury is the interplay between virus binding to the angiotensin-converting enzyme 2 receptor and the impact this action has on the renin-angiotensin system, the body’s innate immune response, and the vascular response to cytokine production. The purpose of this review was to describe the mechanisms underlying cardiovascular injury, including that of thromboembolic disease and arrhythmia, and to discuss their clinical sequelae., Central Illustration, Highlights • The cardiovascular system is affected in diverse ways by severe acute respiratory syndrome coronavirus 2 infection (COVID-19). • Myocardial injury can be detected in ∼25% of hospitalized patients with COVID-19 and is associated with an increased risk of mortality. • Described mechanisms of myocardial injury in patients with COVID-19 include oxygen supply–demand imbalance, direct viral myocardial invasion, inflammation, coronary plaque rupture with acute myocardial infarction, microvascular thrombosis, and adrenergic stress.

Visual Abstract, Highlights • EVs derived from young, but not aged, MSCs rejuvenate senescent EPCs in vitro, recapitulating the effect of MSC transplantation. • Aged MSCs can be genetically modified to produce tailored EVs with increased EPC rejuvenation capacity in vitro and increased angiogenesis capacity following ischemic event in vivo. • EVs represent a promising platform to develop an acellular therapeutic approach in regenerative medicine for cardiovascular diseases., Summary Mesenchymal stromal cell (MSC) transplantation is a form of the stem-cell therapy that has shown beneficial effects for many diseases. The use of stem-cell therapy, including MSC transplantation, however, has limitations such as the tumorigenic potential of stem cells and the lack of efficacy of aged autologous cells. An ideal therapeutic approach would keep the beneficial effects of MSC transplantation while circumventing the limitations associated with the use of intact stem cells. This study provides proof-of-concept evidence that MSC-derived extracellular vesicles represent a promising platform to develop an acellular therapeutic approach that would just do that. Extracellular vesicles are membranous vesicles secreted by MSCs and contain bioactive molecules to mediate communication between different cells. Extracellular vesicles can be taken up by recipient cells, and once inside the recipient cells, the bioactive molecules are released to exert the beneficial effects on the recipient cells. This study, for the first time to our knowledge, shows that extracellular vesicles secreted by MSCs recapitulate the beneficial effects of MSCs on vascular repair and promote blood vessel regeneration after ischemic events. Furthermore, MSCs from aged donors can be engineered to produce extracellular vesicles with improved regenerative potential, comparable to MSCs from young donors, thus eliminating the need for allogenic young donors for elderly patients.

Opioids have the highest rate of illicit drug consumption after cannabis worldwide. Opium, after tobacco, is still the most commonly abused substance in the Middle East. In addition to the ease of availability, one reason for the high consumption of opium in Asian countries might be a traditional belief among Eastern people and even medical staff that opium may have ameliorating effects on cardiovascular diseases (CVDs) as well as diabetes mellitus, hypertension, and dyslipidemia. Over the last decade, many studies have been performed on humans and animals to evaluate the interplay between opium consumption and stable coronary artery disease, acute coronary syndromes, and atherosclerosis. In this review, we conclude that opium consumption should be considered a risk factor for CVDs. Healthy individuals, as well as cardiac and diabetic patients, should be informed and educated about the hazardous effects of opium consumption on cardiovascular and other chronic diseases.

A 68-year-old man presented following a cardiac arrest. Cardiopulmonary resuscitation was performed by the Lund University Cardiopulmonary Assist System (LUCAS), a mechanical chest compression device. Investigations revealed an aortic dissection, which was likely an iatrogenic injury from mechanical cardiopulmonary resuscitation by LUCAS. This case highlights this potential complication. (Level of Difficulty: Beginner.), Graphical abstract

Background Whether cardiovascular (CV) disease risk factors and biomarkers associate differentially with heart failure (HF) risk in men and women is unclear. Objectives The purpose of this study was to evaluate sex-specific associations of CV risk factors and biomarkers with incident HF. Methods The analysis was performed using data from 4 community-based cohorts with 12.5 years of follow-up. Participants (recruited between 1989 and 2002) were free of HF at baseline. Biomarker measurements included natriuretic peptides, cardiac troponins, plasminogen activator inhibitor-1, D-dimer, fibrinogen, C-reactive protein, sST2, galectin-3, cystatin-C, and urinary albumin-to-creatinine ratio. Results Among 22,756 participants (mean age 60 ± 13 years, 53% women), HF occurred in 2,095 participants (47% women). Age, smoking, type 2 diabetes mellitus, hypertension, body mass index, atrial fibrillation, myocardial infarction, left ventricular hypertrophy, and left bundle branch block were strongly associated with HF in both sexes (p, Central Illustration

The differential diagnosis of true aneurysms and pseudoaneurysms is challenging, and multimodality cardiac imaging is often necessary. We report a case in which the limitations of these techniques are exposed, showing that post-operative evaluation of tissue layers remains the gold standard in establishing this diagnosis. (Level of Difficulty: Beginner.), Graphical abstract

A significant concern in current coronavirus disease-2019 (COVID-19) pandemic era is delay in first medical contact in patients with ST-segment elevation myocardial infarction (STEMI), due to reluctance to visit the hospital. We report a case of delayed presentation of STEMI as ventricular septal rupture during the COVID-19 pandemic, a rare presentation in the current age of primary percutaneous coronary intervention. (Level of Difficulty: Beginner.), Graphical abstract, A significant concern in current coronavirus disease 2019 (COVID-19) pandemic era is delay in first medical contact in patients with ST-segment elevation…

The detection of spontaneous coronary artery dissection (SCAD) causing myocardial infarction is integral in pursuing the appropriate management. Our case posed a diagnostic challenge, with Takotsubo cardiomyopathy and coronary embolism among the potential differential diagnoses upon the initial presentation. Extensive propagation of spontaneous coronary artery dissection subsequently resulted in a significant challenge to management requiring surgical revascularization. (Level of Difficulty: Intermediate.), Graphical abstract, The detection of spontaneous coronary artery dissection (SCAD) causing myocardial infarction is integral in pursuing the appropriate management. Our case posed a diagnostic challenge…

Coronary artery fistula (CAF) is an abnormal connection between a coronary artery and a heart chamber resulting in left-to-right shunt. A large CAF was an unexpected cause of heart failure in a 58-year-old woman who underwent transcatheter closure of the CAF with improvement in symptoms but complicated by myocardial infarction. (Level of Difficulty: Beginner.), Graphical abstract, Coronary artery fistula (CAF) is an abnormal connection between a coronary artery and a heart chamber resulting in left-to-right shunt. A large CAF…

Intravascular lithotripsy (IVL) may be useful to deliver Impella devices in patients with peripheral arterial disease. Twelve patients were treated with peripheral IVL prior to Impella insertion. A total of 100% of patients underwent successful device implantation with no IVL complications. IVL can facilitate transfemoral access for Impella insertion. (Level of Difficulty: Advanced.), Graphical abstract, Intravascular lithotripsy (IVL) may be useful to deliver Impella devices in patients with peripheral arterial disease. Twelve patients were treated…

Introduction: Patients undergoing left atrial appendage closure (LAAC) are often severly anemic and close to the transfusion threshold. The aim was to investigate the prevalence of severe anemia in this cohort and if procedural safety is compromised compared with non-anemic patients. Methods and results: Comparison of severly anemic patients (Hb

This is a case of a chronic left ventricular pseudoaneurysm after inferior myocardial infarction that remained clinically silent for 5 years before presenting with sudden rupture, leading to hemopericardium and cardiac tamponade. We discuss the importance of surveillance for left ventricular pseudoaneurysms, the limitations of echocardiography, and the critical role of computed tomography angiography imaging to establish the diagnosis and guide therapy. (Level of Difficulty: Beginner.), Graphical abstract, This is a case of a chronic left ventricular pseudoaneurysm after inferior myocardial infarction that remained clinically silent for 5 years before…

Objectives The purpose of this study was to evaluate ischemic and bleeding outcomes of unselected cancer patients undergoing percutaneous coronary intervention (PCI). Background The number of cancer patients undergoing PCI is increasing despite concerns regarding ischemic and bleeding risks. Methods Between 2009 and 2017, consecutive patients undergoing PCI were prospectively included in the Bern PCI Registry. Cancer-specific data including type, date of initial diagnosis, and health status at index PCI were collected. We performed propensity score matching to adjust for baseline differences between patients with and without cancer. The primary ischemic endpoint was the device-oriented composite endpoint (cardiac death, target vessel myocardial infarction, target lesion revascularization) at 1 year, and the primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) 2 to 5 at 1 year. Results Among 13,647 patients, 1,368 (10.0%) had an established diagnosis of cancer. The 3 leading cancer types were prostate (n = 294), gastrointestinal tract (n = 188), and hematopoietic (n = 177). At index PCI, 179 (13.1%) patients were receiving active cancer treatment. In matched analysis, there was no significant difference in device-oriented composite endpoint (11.5% vs. 10.2%; p = 0.251), whereas cardiac death and BARC 2 to 5 bleeding occurred more frequently among patients with cancer compared with those without cancer (6.8% vs. 4.5%; p = 0.010 and 8.0% vs. 6.0%; p = 0.026, respectively). Cancer diagnosis within 1 year before PCI emerged as an independent predictor for cardiac death and BARC 2 to 5 bleeding at 1 year. Conclusions Cancer patients carry an increased risk of cardiac mortality that was not associated with stent-related ischemic events among patients undergoing PCI in routine clinical practice. Higher risk of bleeding in cancer patients undergoing PCI deserves particular attention. (CARDIOBASE Bern PCI Registry; NCT02241291), Central Illustration

Cardiovascular disease is the leading cause of death globally. Cardiomyocytes (CMs) have poor regenerative capacity, and pharmacological therapies have limited efficacy in severe heart failure. Currently, there are several promising strategies for cardiac regeneration. The most promising approach to remuscularize failing hearts is cell transplantation therapy using newly generated CMs from exogenous sources, such as pluripotent stem cells. Alternatively, approaches to generate new CMs from endogenous cell sources in situ may also repair the injured heart and improve cardiac function. Direct cardiac reprogramming has emerged as a novel therapeutic approach to regenerate injured hearts by directly converting endogenous cardiac fibroblasts into CM-like cells. Through cell transplantation and direct cardiac reprogramming, new CMs can be generated and scar tissue reduced to improve cardiac function; therefore, cardiac regeneration may serve as a powerful strategy for treatment of severe heart failure. While substantial progress has been made in these two strategies for cardiac regeneration over the past several years, challenges remain for clinical translation. This review provide an overview of previous reports and current challenges in this field. Keywords: Regeneration, Pluripotent stem cells, Direct reprogramming, Fibroblasts, Cardiomyocytes