Our understanding of the genetic basis of cardiovascular diseases (CVDs) has evolved rapidly. This has resulted from a combination of dedicated research in well phenotyped CVD patients, the sequencing of the human genome, and the ready accessibility and decreasing cost of next-generation sequencing technologies. This increased knowledge of the genetic basis of CVDs has heralded the era of precision medicine. This encompasses many elements including improved diagnosis, family screening, assistance with reproductive decisions, targeted therapeutics guided by both phenotype and genotype, and providing important insights into risk stratification and prognosis. Furthermore, novel insights into genetic mechanisms, clinical rollout of polygenic risk scores for common CVDs, and the promise of genome editing approaches to effectively cure disease represent some of the exciting future endeavors that will change established clinical approaches. This Part 1 of a 5-part series focuses on the underpinnings and fundamental aspects of precision medicine.
  Obesity is associated with increased cardiovascular risk; however, the potential role of dysregulations in the adipose tissue (AT) metabolome is unknown.
 
  The aim of this study was to explore the role of dysregulation in the AT metabolome on vascular redox signaling and cardiovascular outcomes.
 
  A screen was conducted for metabolites differentially secreted by thoracic AT (ThAT) and subcutaneous AT in obese patients with atherosclerosis (n=48), and these metabolites were then linked with dysregulated vascular redox signaling in 633 patients undergoing coronary bypass surgery. The underlying mechanisms were explored in human aortic endothelial cells, and their clinical value was tested against hard clinical endpoints.
 
  Because ThAT volume was associated significantly with arterial oxidative stress, there were significant differences in sphingolipid secretion between ThAT and subcutaneous AT, with C160-ceramide and derivatives being the most abundant species released within adipocyte-derived extracellular sed plasma C160-ceramide and C160-glycosylceramide changes compared with control subjects.
 
  These results demonstrate for the first time in humans that AT-derived ceramides are modifiable regulators of vascular redox state in obesity, with a direct impact on cardiac mortality in advanced atherosclerosis. (The Interaction Between Appetite Hormones; NCT02094183).
 These results demonstrate for the first time in humans that AT-derived ceramides are modifiable regulators of vascular redox state in obesity, with a direct impact on cardiac mortality in advanced atherosclerosis. (The Interaction Between Appetite Hormones; NCT02094183).
  Several clinical and cardiac magnetic resonance (CMR)-derived parameters have been shown to be associated with death or heart transplant late after the Fontan operation.
 
  The objective of this study was to identify the relative importance and interactions of clinical and CMR-based parameters for risk stratification after the Fontan operation.
 
  Fontan patients were retrospectively reviewed. Clinical and CMR parameters were analyzed using univariable Cox regression. The primary endpoint was time to death or (listing for) heart transplant. To identify the patients at highest risk for the endpoint, classification and regression tree survival analysis was performed, including all significant variables from Cox regression.
 
  The cohort consisted of 416 patients (62% male) with a median age of 16 years (25th, 75th percentiles 11, 23 years). Over a median follow-up of 5.4 years (25th, 75th percentiles 2.4, 10.0 years) after CMR, 57 patients (14%) reached the endpoint (46 deaths, 7 heart transplants, 4 heart trans risk.  https://www.selleckchem.com/products/ly2157299.html  These data highlight the value of integrating CMR and clinical parameters for risk stratification in this population.
  Published data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear.
 
  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.
 
  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).
 
  In 144 ST-segment elevation myocardial infar STEMI patients.
 In this multicenter international registry, COVID-19-positive ACS patients presented later and had increased in-hospital mortality compared with a pre-COVID-19 ACS population. Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients.
  There are conflicting data on the impact of implantable cardioverter-defibrillator (ICD) shocks on subsequent mortality.
 
  The aim of this study was to determine whether the arrhythmic substrate leading to ICD therapy or the therapy itself increases mortality.
 
  The study cohort included 5,516 ICD recipients who were enrolled in 5 landmark ICD trials (MADIT-II, MADIT-RISK, MADIT-CRT, MADIT-RIT, RAID). The authors evaluated the association of device therapy with subsequent mortality in 4 separate time-dependent models model I, type of ICD therapy; model II, type of arrhythmia for which ICD therapy was delivered; model III, combined assessment of all arrhythmia and therapy types during follow-up; and model IV, incremental risk associated with repeated ICD shocks.
 
  When analyzed by the type of ICD therapy (model I), a first appropriate ICD shock was associated with increased risk of subsequent mortality with or without concomitant occurrence of inappropriate shock during follow-up (hazard ratio [HR] 2.78 and 2.