What will surgical coronary revascularization look like in 25 years? Purpose of review Coronary artery bypass grafting evolved in incremental but significant steps since its introduction. Here, we provide an update on operative techniques, choice of conduits, patient selection/decision-making and primary and secondary prevention measures with potential of influencing the future of coronary artery bypass grafting (CABG) surgery. Recent findings Associated mortality of off-pump CABG (OPCAB) procedures performed in high-volume OPCAB centers (≥164 cases per year) and by experienced surgeons (≥48 cases per year) was reduced compared with on-pump CABG with two or more grafts suggesting a volume-based dependency of outcomes in CABG procedures with high-technical complexity. Ten-year results from the recent Arterial Revascularization Trial showed no significant between-group difference for the primary and secondary outcome. Total arterial revascularization using composite bilateral internal mammary artery-Y-conduits through a limited access mini-thoracotomy was not only shown to be feasible but a safe and reproducible procedure with excellent midterm outcomes. The most recent Randomized Trial of Endoscopic or Open Vein-Graft Harvesting for Coronary-Artery Bypass (REGROUP) trial demonstrated no significant difference between open vein-graft harvesting and endoscopic vein-graft harvesting in the occurrence of major adverse cardiac events. Summary Adherence to the most recent guidelines on myocardial revascularization is a key component for providing state-of the CABG surgery. Trends to lesser invasiveness in surgical coronary revascularization will gain momentum and is expected – with further improvements – to be the mainstay of future surgical coronary revascularization strategies. Correspondence to Etem Caliskan, MD, Department of Cardiovascular Surgery, Charité-Universitätsmedizin Berlin, Berlin, Germany. Tel: +00 49 30 450 665020; e-mail: ibrahim-etem.caliskan@charite.de Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Modulation of cholesterol efflux capacity in patients with myocardial infarction Purpose of review Epidemiologic studies consistently demonstrated that patients with coronary artery disease (CAD) and low HDL cholesterol (HDL-C) are more likely to develop major adverse cardiovascular events as compared with those with normal or high HDL. However, several large randomized trials failed to demonstrate that a substantial, pharmacological-based, increase of HDL-C concentrations results in a clinically significant reduction of ischemic outcomes. This has been largely attributed to the fact that, although these drugs are able to raise the HDL-C concentration, they have no effect on HDL-C atheroprotective function. Subsequently, the ‘HDL hypothesis’ evolved, and the focus shifted from raising the concentration of HDL-C to raising the reverse cholesterol transport (RCT) function by increasing patients cholesterol efflux capacity (CEC) instead. Indeed, new data suggest that HDL-C metabolism and the ability of the HDL molecule to transport cholesterol from the atherosclerotic plaque to the liver, measured by the CEC, is more important than steady-state HDL-C levels. Modulation of the CEC has become, therefore, a promising therapeutic target in CAD patients. This article reviews the current data on the ‘cholesterol efflux hypothesis’ and discuss its ability to be modulated has a potential therapeutic target. Recent findings Recent data have demonstrated that impaired serum CEC was associated with increased mortality after a myocardial infarction (MI). Thus, therapeutic intervention aiming to improve CEC and RCT may reduce the risk of recurrent events. Early phase clinical studies targeting CEC showed promising results and a megatrial is ongoing testing the hypothesis that an improved RCT trough a modulation of the CEC can modify patient's prognosis after an acute MI. Summary The ‘cholesterol efflux hypothesis’ is now supported by several clinical studies and is being tested with a therapeutic candidate in a megatrial enrolling high-risk patient with MI. Correspondence to Prof Gilles Montalescot, Sorbonne Université, ACTION Study Group, INSERM UMRS 1166, Département de Cardiologie, Institut de Cardiologie, Hôpital de la Pitié-Salpêtrière (APHP), Bureau 1, 47-83 bld de l’Hôpital, 75013 Paris, France. Tel: +33 142163001; fax: +33 142162931; e-mail: gilles.montalescot@aphp.fr Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Cardiovascular risk reduction with icosapent ethyl Purpose of review Residual risk for atherosclerotic cardiovascular disease (ASCVD) persists even among patients with optimal low-density lipoprotein cholesterol (LDL-C) levels. Randomized trials attempting to modulate other lipids beyond LDL-C have failed to demonstrate significant reductions in ischemic events. Recent findings Mounting evidence suggests that triglyceride elevation is an independent risk factor for ASCVD. Though trials of triglyceride-lowering therapy in the statin era have failed to provide protection from ASCVD events, subgroup analyses have revealed that those with the highest triglycerides at time of enrollment appeared to receive the greatest clinical benefit. REDUCE-IT was a trial that enrolled patients with high triglycerides despite having goal LDL-C levels on statin therapy. Treatment with icosapent ethyl, a highly purified omega-3 fatty acid (OM3FA), eicosapentaenoic acid ethyl ester, provided a 25% relative risk reduction for the primary composite cardiovascular endpoint (hazard ratio 0.75, 95% CI 0.68--0.83; P = 0.00000001), as well as a 30% relative risk reduction in total ischemic events (P = 0.00000000036). Summary Icosapent ethyl was rigorously shown to decrease residual risk for cardiovascular events, though the benefits seen were likely because of mechanisms beyond mere triglyceride lowering. Clinical application of icosapent ethyl in this cohort of patients with residual risk is urgently needed. Correspondence to Deepak L. Bhatt, MD, MPH, Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. Tel: +1 857 307 1992; fax: +1 857 307 1955; e-mail: dlbhattmd@post.harvard.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Takotsubo syndrome: diagnostic work-up and clues into differential diagnosis Purpose of review Takotsubo syndrome represents an increasingly recognized clinical entity characterized by a reversible acute myocardial dysfunction, often triggered by an emotional or physical stress, and independent of an underlying epicardial coronary artery disease. The diagnosis is often challenging because of the nonspecific clinical presentation and the inconclusive noninvasive diagnostic imaging. Recent findings The present review provides a brief overview of Takotsubo syndrome clinical presentation and guides the clinician through the diagnostic work-up of Takotsubo syndrome, highlighting clues into differential diagnosis. A review of clinical management is also provided. Summary Despite increasing awareness and recognition, the diagnosis of Takotsubo syndrome remains challenging and Takotsubo syndrome is often underdiagnosed or misdiagnosed. The prompt recognition of Takotsubo syndrome portends relevant prognostic and therapeutic implications. Correspondence to Antonio Abbate, ‘Roberts’ Professor of Cardiology, VCU Pauley Heart Center, Department of Internal Medicine, Division of Cardiology, West Hospital, West Wing 5-020, 1200 E Broad Street, P.O. Box 980204, Richmond, VA 23298, USA. Tel: +1 804 828 0513; e-mail: antonio.abbate@vcuhealth.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Carotid artery stenting: an update Purpose of review To present the latest evidence about carotid artery stenting (CAS) including indications, safety, efficacy, and available equipment. Recent findings The micromesh stent, a new stent design which offers excellent flexibility and embolic protection, has been associated with promising outcomes. Summary CAS has emerged as a minimally invasive treatment method for carotid artery stenosis with comparable outcomes with surgical management. The implementation of new technology combined with operator experience has led to a paradigm shift; however, to date, no robust evidence exists about patient and lesion selection. Many studies are underway to clarify the technical aspects of CAS as well as the optimal treatment of carotid artery stenosis for each patient population. Correspondence to Stavros Spiliopoulos, MD, PhD, EBIR, FCIRSE, Asst. Professor of Interventional Radiology Unit, 2nd Department of Radiology, School of Medicine, National and Kapodistrian University of Athens, Attikon University General Hospital, Athens, Greece. Tel: +30 6937403468/+30 2105831832; e-mail: stavspiliop@med.uoa.gr,stavspiliop@gmail.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Genetics of early-onset coronary artery disease: from discovery to clinical translation Purpose of review This review is a comprehensive update on recent discoveries on the genetics of early-onset coronary artery disease (EOCAD), and how those findings can be translated to advance its medical management. Recent findings To date, a total of 266 common variants of modest effect size have been reported to be associated with CAD, but many still warrant functional studies. Rare variants impacting the function of at least 10 genes are now well characterized in Mendelian EOCAD. Estimations of minor allele frequencies in multiple ancestries from large genetic databases have allowed us to estimate the prevalence of Mendelian forms of EOCAD. In fact, the prevalence of Mendelian mutations varies markedly between ancestries, ranging from 1 : 289 to 1 : 153 for familial hypercholesterolemia. Mendelian forms of EOCAD support three major biological pathways, including lipid metabolism, vascular wall integrity and function, and thrombosis. Furthermore, combining common variants of modest effect into polygenic risk scores (PRS) has shown to be effective at identifying individuals at high risk of CAD. Summary Mendelian forms of EOCAD highlight the importance of lipid metabolism, yet prevalence in many non-European populations remains to be clarified. Polygenic EOCAD affects more individuals and, in many cases, confers a higher risk of EOCAD than rare Mendelian mutations. Thus, sequencing of target genes and the derivation of PRSs can be used to identify high-risk patients, leading to more personalized therapeutic approaches. Correspondence to Guillaume Paré, MD, MSc, FRCPC, McMaster University, Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Institute, 237 Barton St. East – C4 126, Hamilton, ON, Canada L8L 2X2. Tel: +1 905 527 4322 x40365; fax: +1 905 297 3789; e-mail: pareg@mcmaster.ca Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.co-cardiology.com). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Review of cardiovascular outcomes trials of sodium–glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists Purpose of review In recent years, there have been several cardiovascular outcomes trials (CVOT) of two new classes of glucose-lowering medications: sodium–glucose cotransporter-2 inhibitors (SGLT2-i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA). It is important examine their potential for cardiovascular benefit and possible side effects among patients with type 2 diabetes (T2D) mellitus. Recent findings The current article reviews the findings of recent CVOT of SGLT2-i and GLP-1 RA, including their impact on cardiovascular events and relevant side effects. Summary For all T2D patients, with or without established cardiovascular disease, the SGLT2-i have demonstrated impressive reductions in hospitalization for heart failure and renoprotection. For T2D patients with established cardiovascular disease, SGLT2-i demonstrated an additional benefit of reduced major adverse cardiac events, on top of reductions in hospitalizations for heart failure, renoprotection, and in some instances, mortality. Similarly, all GLP-1 RA CVOTs demonstrated noninferiority compared with placebo for safety. In comparison, GLP-1 RA appear to preferentially reduce ischemic events (stroke or myocardial infarction) over hospitalization for heart failure, and demonstrated renoprotection in several of the CVOTs. Correspondence to Jonathan D. Newman, MD, MPH, Division of Cardiology and Center for the Prevention of Cardiovascular Disease, Department of Medicine, New York University School of Medicine, 227 E. 30th St., Ste. 853, New York, NY 10016, USA. Tel: +1 212 263 9393; fax: +1 646 501 2659; e-mail: Jonathan.Newman@nyumc.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Sustainability of blood pressure reduction in black barbershops Purpose of review The prevalence of hypertension (HTN) among non-Hispanic blacks increased from 41 to 55% with the release of the new 2017 ACC/AHA guidelines – the highest among any racial group. Non-Hispanic black men have less physician interaction and lower blood pressure (BP) treatment and control rates when compared with their female counterparts, necessitating community outreach. Here, we review the Los Angeles Barbershop Blood Pressure Study (LABBPS) which demonstrated a community-based approach involving pharmacists, physicians, and barbers could improve BP control rates among black men. Recent findings LABBPS was a cluster-randomized trial that evaluated both the efficacy and sustainability of a pharmacist-led HTN management program in which barbers promoted follow-up with pharmacists who prescribed antihypertensive therapy under collaborative practice agreements with intervention participant's primary care providers. After 6 months researchers observed a 21 mmHg greater fall in SBP among intervention group participants when compared with the control group participants who received ‘usual care.’ The 6-month extension phase of the study showed that the impressive BP reduction achieved was sustained with less pharmacist contact. Summary Multidisciplinary, community-based approaches to HTN management can be effective and are necessary to tackle the current disparity seen in BP control rates. The model developed in LABBPS represents one such approach. Correspondence to Ciantel A. Blyler, PharmD, Cedars-Sinai Medical Center, Smidt Heart Institute, 127 S. San Vicente Blvd., Ste. A3408, Los Angeles, CA 90048, USA. Tel: +1 310 425 2904; fax: +1 310 967 3818; e-mail: Ciantel.Blyler@cshs.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Vitamin D supplements and prevention of cardiovascular disease Purpose of review The role of vitamin D supplementation for prevention of cardiovascular disease (CVD) outcomes has been rigorously studied only recently. This review briefly summarizes results from recent randomized controlled trials in the context of prior laboratory and epidemiologic data. Recent findings Randomized trials of vitamin D that included CVD outcomes, as well as two recently published large population-based trials that prespecified CVD as a primary endpoint (The Vitamin D Assessmentand The VITamin D and OmegA-3 TriaL), indicate that vitamin D supplementation does not decrease CVD incidence, when compared with placebo. Summary Evidence to date suggests that vitamin D supplementation in the general community does not reduce the risk of major cardiovascular events. Other trials are ongoing and future studies will explore additional CVD outcomes such as heart failure and assess high-risk populations such as those with chronic kidney disease. Correspondence to JoAnn E. Manson, MD, DrPH, Department of Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue, 3rd Fl, Boston, MA 02215, USA. Tel: +1 617 278 0871; fax: +1 617 731 3843; e-mail: jmanson@rics.bwh.harvard.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Genetic testing for aortopathies: primer for the nongeneticist Purpose of review Although the majority of thoracic aortic aneurysms and dissections (TAD) in the overall population are mainly related to arterial hypertension and atherosclerosis, Heritable Thoracic Aortic Disease (HTAD) are increasingly recognized, especially in younger individuals. As fatal events in the setting of HTAD are preventable with timely detection and appropriate management, this review aims to provide an overview of the genetic basis of HTAD and practical recommendations for genetic evaluation in this setting. Recent findings Thanks in part to a number of important efforts to set up (inter)national networks and consortia for collecting clinical and genetic data from patients with these rare disorders, significant progress has been made in understanding the natural evolution of these disorders. These insights are now starting to enable the development of recommendations for the management of these patients. In addition, pathogenic variants in a number of new genes have been identified in HTAD patients. On the basis of more extensive genetic screening in cohorts of patients with TAD, it is becoming clear that there is no strict boundary between syndromal and nonsyndromal HTAD entities. It is, therefore, important to at least consider genetic evaluation, not only for patients presenting with syndromic forms but also for more isolated TAD. Finally, there are indications that we will -- up to a certain point -- soon be able to draw up a more precise policy for individual patients, based on the underlying genetic defects Summary Genetic evaluation in (young) patients with both syndromic and nonsyndromic forms of HTAD should be considered and is helpful for the development of more precise medicine. Correspondence to Julie De Backer, MD, PhD, Department of Cardiology and Center for Medical Genetics, Ghent University Hospital, C. Heymanslaan 10, 9000 Ghent, Belgium. Tel: +32 9 332 56 27; e-mail: julie.debacker@ugent.be Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.