Spontaneous coronary artery dissection: update 2019 Purpose of review Spontaneous coronary artery dissection (SCAD) is an important cause of myocardial infarction (MI) in women with few or no conventional cardiovascular risk factors. Lack of awareness about this condition among healthcare providers had led to significant underdiagnosis and misdiagnosis in this relatively young patient population. Recent findings The current review summarizes the contemporary data on cause, management strategies and outcomes of SCAD. Summary SCAD is not as rare as previously thought, accounting for up to 4% of all acute coronary syndromes. It is frequently linked with predisposing factors, such as fibromuscular dysplasia or other vasculopathies, and is often triggered by physical or emotional stress. Due to more fragile vessel architecture, coronary angiography as the first-line diagnostic tool should be performed meticulously to avoid iatrogenic dissection. Intravascular imaging may be required if angiographic findings are uncertain. Unless patients have high-risk features such as ongoing ischemia, recurrent chest pains, left main artery dissection, ventricular arrhythmias, or hemodynamic instability, a conservative treatment strategy is favored over revascularization. Close monitoring is essential after a SCAD-event as recurrent cardiovascular events post-SCAD are frequent. Correspondence to Jacqueline Saw, Interventional Cardiology, Vancouver General Hospital; Clinical Professor, University of British Columbia, 2775 Laurel Street, Level 9, Vancouver, BC, Canada V5Z1M9. Tel: +1 604 875 5547; fax: +1 604 875 5563; e-mail: jsaw@mail.ubc.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Renal insufficiency and severe coronary artery disease: should coronary artery bypass grafting, off-pump coronary artery bypass grafting or percutaneous coronary intervention be performed? Purpose of review Chronic kidney disease (CKD) is an important determinant of long-term survival. However, the optimal revascularization strategy for patients with CKD is still controversial. Herein we review the impact of different treatment modalities on the outcomes of patients with CKD. Recent findings CABG could confer better long-term outcomes than PCI in patients with CKD, irrespective of CKD severity. CABG as compared with PCI may be associated with improved long-term survival albeit higher short-term risk. Off-pump as compared with on-pump CABG may be associated with better short-term outcomes but no demonstrable long-term benefit. In CKD patients who are treated with PCI, the use of drug-eluting stents may be associated with better intermediate-term outcomes than bare metal stents. Summary There is insufficient evidence to inform the optimal revascularization strategy for patients with CKD and severe coronary artery disease. CABG as compared with PCI confers greater long-term benefit but higher upfront risk. A multidisciplinary, team-based evaluation based on individual patient comorbidity, frailty and anatomical disease burden, is recommended when making treatment decisions. Correspondence to Louise Y. Sun, MD, SM, FRCPC, Division of Cardiac Anesthesiology, University of Ottawa Heart Institute, Rm H-2206, 40 Ruskin Street, Ottawa, ON, Canada K1Y 4W7. Tel: +1 613 696 7381; fax: +1 613 696 7099; e-mail: lsun@ottawaheart.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Cardiometabolic risk reduction after metabolic surgery Purpose of review Metabolic surgery provides the largest and most durable weight loss in persons with obesity. There is abundant randomized evidence to show its superiority over medical treatment alone, in achieving improved glycemic control. Recent findings Recent trials have also demonstrated a significant reduction in cardiovascular risk factor burden, whereas data from observational studies suggest an ability to reduce overt cardiovascular events and mortality. Summary In this review, we briefly describe the surgical procedures involved and their indications. We further provide a summary of the effects of metabolic surgery on weight loss, glycemic control, and clinical outcomes. Correspondence to Deepak L. Bhatt, MD, MPH, Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. Tel: +1 857 307 1992; e-mail: dlbhattmd@post.harvard.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

The role of coronary reactivity testing in women with no obstructive coronary artery disease Purpose of review Two-thirds of women with signs and symptoms of ischemia and no obstructive coronary artery disease (INOCA) have abnormal coronary reactivity. These women are challenging to assess, diagnose and manage because of a lack of evidence-based guidelines. Furthermore, they are considered to be at ‘low risk’ by most physicians, often receive no specific therapy and tend to be dismissed from subspecialty care. Recent findings Coronary reactivity testing (CRT) is considered the reference-standard for evaluation of epicardial and microvascular coronary function in response to various vasoactive agents. It provides a comprehensive vascular function assessment for diagnosis, a guide for management, and has prognostic benefit that outweighs the risk of the procedure. We recently demonstrated the prognostic value of assessing coronary vascular reactivity in women with signs and symptoms of ischemia, especially those with no obstructive coronary artery disease. Summary Invasive CRT is a feasible, useful method to identify coronary microvascular dysfunction (CMD) and risk stratify women with INOCA. It has a comparable safety record with other invasive procedures. Future research is directed at optimizing patient selection, streamlining of invasive CRT methods using user-friendly catheters to enhance feasibility in the routine clinical setting, and optimizing treatment protocols, with clinical trials designed to evaluate outcomes. Correspondence to C. Noel Bairey Merz, MD, FAHA, FACC, FESC, Barbra Streisand Women's Heart Center, Cedars-Sinai Smidt Heart Institute, Los Angeles, 127 S. San Vicente Blvd, Suite A3600, Los Angeles, CA 90048, USA. Tel: +1 310 423 9680; fax: +1 310 423 9681; e-mail: Noel.BaireyMerz@cshs.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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 This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 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.