Functional Mitral Regurgitation in Heart Failure. Erratum. No abstract available

Aspirin for the Primary Prevention of Cardiovascular Disease: A Review of the Literature and Considerations for Clinical Practice Cardiovascular disease is the leading cause of death globally, and deaths due to coronary heart disease or stroke account for over half of all cardiovascular deaths in the United States. While many important advances have been made in the treatment and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), morbidity and mortality remain high. Aspirin has been commonly used for the primary and secondary prevention of ASCVD for decades and is an easily accessible therapeutic option. While it is a cornerstone of secondary prevention, its role in primary prevention is less clear and professional guidelines have differed in their recommendations. As literature has substantially evolved over the last 40 years, so too has our understanding of aspirin’s role in the primary prevention of ASCVD. This article reviews landmark clinical trials of aspirin in primary prevention, and highlights key changes in dosing strategies and demographics. All Authors – nothing to disclose. Address for Correspondence: Jonathan Cicci, PharmD, 101 Manning Drive, CB 7600, Chapel Hill, NC 27514, jcicci@unch.unc.edu, T: 984.974.0229/F:984.974.7163 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Cardiovascular Disorders Mediated by Autonomic Nervous System Dysfunction Cardiovascular disorders, such as orthostatic hypotension and supine hypertension, are common in patients with neurodegenerative synucleinopathies such as Parkinson disease (PD), and may also occur in other conditions, such as peripheral neuropathies, that result in autonomic nervous system (ANS) dysfunction. Dysfunction and degeneration of the ANS are implicated in the development of orthostatic and postprandial hypotension and impaired thermoregulation. Neurogenic orthostatic hypotension (nOH) results from sympathetic failure and is a common autonomic disorder in PD. Supine hypertension may also occur as a result of both sympathetic and parasympathetic dysfunction in conjunction with nOH in the majority of patients with PD. Management of supine hypertension in the setting of nOH can be counterintuitive and challenging. Additionally, the presence of other non-cardiovascular comorbidities, such as diabetes mellitus and peripheral edema, may further contribute to the burden of disease. ANS dysfunction thus presents major healthcare implications and challenges for neurology and cardiovascular practices, necessitating an integrated neurology and cardiology management approach. Source of support: Lundbeck Disclosures: P Khemani has served as a speaker for TEVA and St. Jude and as an advisory board attendee for Allergan and Lundbeck. AA Mehdirad has served as a speaker for Lundbeck, Pfizer, and Bristol-Myers Squibb. The authors received no direct compensation related to the development of the manuscript. Acknowledgments: Medical writing assistance was provided by the CHC Group (North Wales, PA, USA) and was supported by Lundbeck. Corresponding author: Ali A. Mehdirad, MD, FACC, Chief, Medicine Service, Carl Vinson VA Medical Center, 1826 Veterans Blvd., Dublin, GA 31021, Telephone: 478-272-1210 Fax: 478-272-2717, Email: Ali.Mehdirad@va.gov Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Lipoprotein(a) Testing and Emerging Therapies The study of lipoprotein(a) [Lp(a)] over the years has been a source of both enlightenment and frustration for the medical community. Accumulating evidence from large sample observational studies, Mendelian randomization studies, and genome-wide association studies has strengthened the association between Lp(a) and the development of atherosclerotic cardiovascular disease. This evidence supports the testing of Lp(a) in certain high risk populations in order for clinicians to improve the risk profile of patients. Despite a variety of medical therapies that have been proven to reduce Lp(a) levels, the connection between the medical management of serum Lp(a) and improved cardiovascular outcomes remains elusive, due to the lack of specificity that current therapies have in targeting the Lp(a) production pathway. A new frontier in Lp(a) research has emerged with antisense-oligonucleotide therapy and RNA interference therapy, both of which target Lp(a) production at the level of mRNA translation. These therapies provide a pathway for investigating the effect of medical management of serum Lp(a) on cardiovascular outcomes. No conflict of interest exists in the preparation of this manuscript. Address for Correspondence: William H. Frishman MD, Dept. of Medicine, New York Medical College, 40 Sunshine Cottage Road, Valhalla, NY 10595, William_Frishman@nymc.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Pregnancy Complications as a Window to Future Cardiovascular Disease Pregnancy is a time of significant hemodynamic, metabolic, and hormonal stress that can unmask underlying subclinical cardiovascular abnormalities, and pregnancy-related complications may serve as early warning signs for future risk of cardiovascular disease. The increased recognition of these sex-specific risk factors could identify women who may benefit from more intensive risk factor modification to reduce morbidity and mortality later in life. In this review, we describe several pregnancy-related complications that have been associated with the risk of cardiovascular disease, including hypertensive disorders of pregnancy, gestational diabetes mellitus, preterm delivery, and pregnancy loss. Pregnancy-associated risk factors must be identified to fully assess a woman’s future cardiovascular risk and may influence strategies for risk reduction. Disclosures: The authors have no conflicts of interest to disclose. Corresponding author: Melinda B. Davis, MD, FACC, University of Michigan, 1500 E Medical Center Drive, Ann Arbor, MI 48109-5853, Phone 734-763-6003 (office), Cell Phone 773-412-9881, Fax 734-936-5256, E-mail: davismb@umich.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Left Ventricular Noncompaction: Diagnostic Approach, Prognostic Evaluation, and Management Strategies Left ventricular noncompaction cardiomyopathy is a heart disease with relevant potential complications including heart failure, life-threatening arrhythmias, and embolic events. In order to prevent adverse outcomes, it is crucial to appropriately recognize and manage this cardiomyopathy. In this article, we report the main clinical presentations and imaging modalities used for diagnosis, including echocardiography and magnetic resonance imaging. We highlight the role of a comprehensive functional cardiac evaluation and the possible prognostic implications of both systolic and diastolic dysfunction. Furthermore, we summarize clinical factors and imaging findings which have prognostic significance. Finally, we discuss the main management strategies based on phenotypic expressions which are aimed at treating symptoms and preventing complications. Conflicts of Interest and Source of Funding: This research did not receive any grants from any funding agency in the public, commercial, or non-profit sector. The Authors declare that there is no conflict of interest. Corresponding Author: Stefania Angela Di Fusco, Cardiology Unit, San Filippo Neri Hospial, via Martinotti 20, 00135 Rome, Italy. e-mail: doctstefania@hotmail.com. Phone: 0039 3491500982 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Sudden Cardiac Death in Brugada Syndrome The Brugada syndrome is an inherited channelopathy that alters the main transmembrane ion currents that constitute the cardiac action potential. These changes not only modify the resting electrocardiogram, but also predispose patients to develop malignant ventricular tachyarrhythmias that can lead to syncope, cardiac arrest, and sudden cardiac death. This syndrome is responsible for nearly 20% of all sudden cardiac deaths in patients with structurally normal hearts and up to 12% of all sudden cardiac deaths. Brugada syndrome is diagnosed by its characteristic electrocardiogram consisting of a coved type ST segment elevation of at least 2mm followed by a negative T wave in either one of the right precordial leads. These changes can be observed spontaneously or after administration of a sodium channel blocker. While our understanding of this disease has increased tremendously since its first description in 1992, the primary therapeutic option remains implantation of an implantable cardioverter-defibrillator to avoid sudden cardiac death. Therefore, tremendous effort is being made to effectively risk stratify patients to determine who would benefit from implantable cardioverter-defibrillator implantation. None of the authors have any conflicts of interest to disclose Correspondence to: Wilbert S. Aronow, MD, FACC, FAHA, Professor of Medicine and Director of Cardiology Research, Westchester Medical Center and New York, Medical College, Macy Pavilion, Room 141, Valhalla, NY 10595, USA. E-mail: wsaronow@aol.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Left Atrial Appendage Occlusion in the Management of Stroke in Patients With Atrial Fibrillation Atrial fibrillation (AF) is associated with a substantially higher risk of thromboembolism, particularly stroke events, resulting in significant morbidity and mortality. Oral anticoagulation (OAC), while effective in reducing embolic events in AF patients, is associated with an increased bleeding risk. Thus, not all patients with AF are candidates for OAC and some are only candidates for OAC in the short term. Of the available non-pharmacologic strategies for the management of AF, left atrial appendage occlusion (LAAO) has emerged as a potential approach for reducing the risk of systemic thromboembolism in AF patients eligible for OAC. LAAO can be achieved either surgically or percutaneously utilizing an epicardial, endocardial, or a combined approach. Although available data are limited, currently available LAAO devices, and those being developed, have shown promise in reducing bleeding risk in AF patients due to the reduced overall need for anticoagulation, while maintaining efficacy in preventing thromboembolism. The optimal device will reduce both embolic and hemorrhagic strokes, and other bleeds, with a high implant success rate and a low complication rate. Until that time, anticoagulation remains the gold standard that these devices strive to surpass, and thus LAAO devices are currently indicated in patients with relative contraindication to OAC therapy. Address for Correspondence: Sei Iwai, MD, Westchester Medical Center, 100 Woods Road, Macy Pavilion-Cardiology, Valhalla, NY, 10595., Phone:914-493-6808 Fax: 914-493-1854, Email: sei.iwai@wmchealth.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Vulnerable Plaque: A Review of Current Concepts in Pathophysiology and Imaging Advances in our understanding of the natural history and biology of atherosclerotic vascular disease led to the concept of a vulnerable plaque (VP), which is predisposed towards more rapid progression and acute coronary events. With newer technologies, we now have at our disposal high quality imaging studies, both invasive and noninvasive, which show promise in identifying plaque characteristics that make it more vulnerable. Upcoming trials aim to evaluate the utility of imaging VP in predicting clinical events. We discuss the role of VP imaging in managing atherosclerotic vascular disease. The authors declare no conflict of interest in the preparation of this manuscript. Address for correspondence: Wilbert S. Aronow, MD, FACC, FAHA, Cardiology Division, Westchester Medical Center and New York Medical College, 100 Woods Road, Macy Pavilion, Room 141, Valhalla, NY 10595, Telephone number: (914) 493-5311; fax number: (914) 235-6274, E-mail: wsaronow@aol.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.