Management of Acute Ischemic Stroke Due to Large-Vessel Occlusion: JACC Focus Seminar

Acute ischemic stroke is a severe and life-threatening disease, particularly when caused by a large-vessel occlusion. The only available 2 treatment options are intravenous alteplase and endovascular therapy (mechanical clot removal), both of which are highly time-dependent. Thus, rapid patient transfer, diagnosis, and treatment are crucial, and time-consuming imaging methods and overly selective treatment selection criteria should be avoided. A combined endovascular therapy approach using stent-retrievers and aspiration is the most effective way to achieve fast first-pass complete reperfusion and should thus be used. To diagnose and treat patients as fast as possible, the organization of existing systems of care, and particularly pre-hospital transfer systems, have to be changed. Several different transport models are currently in use because the optimal patient transfer paradigm is highly dependent on local geography and hospital efficiency.     

Management of Intracerebral Hemorrhage: JACC Focus Seminar

Intracerebral hemorrhage (ICH) accounts for a disproportionate amount of stroke-related morbidity and mortality. Although chronic hypertension and cerebral amyloid angiopathy are the underlying cerebral vasculopathies accounting for the majority of ICH, there are a broad range of potential causes, and effective management requires accurate identification and treatment of the underlying mechanism of hemorrhage. Magnetic resonance imaging and vascular imaging techniques play a critical role in identifying disease mechanisms. Modern treatment of ICH focuses on rapid stabilization, often requiring urgent treatment of mass effect, aggressive blood pressure reduction and correction of contributing coagulopathies to achieve hemostasis. We discuss management of patients with ICH who continue to require long-term anticoagulation, the interaction of ICH with neurodegenerative diseases, and our approach to prognostication after ICH. We close this review with a discussion of novel medical and surgical approaches to ICH treatment that are being tested in clinical trials.     

Supplemental Vitamins and Minerals for Cardiovascular Disease Prevention and Treatment: JACC Focus Seminar

This is an update of the previous 2018 systematic review and meta-analysis of vitamin and mineral supplementation on cardiovascular disease outcomes and all-cause mortality. New randomized controlled trials and meta-analyses were identified by searching the Cochrane library, Medline, and Embase, and data were analyzed using random effects models and classified by the Grading of Recommendations Assessment Development and Evaluation approach. This updated review shows similar findings to the previous report for preventive benefits from both folic acid and B vitamins for stroke and has been graded with moderate quality. No effect was seen for the commonly used multivitamins, vitamin D, calcium, and vitamin C, and an increased risk was seen with niacin (with statin) for all-cause mortality. Conclusive evidence for the benefit of supplements across different dietary backgrounds, when the nutrient is sufficient, has not been demonstrated.     

Hyperacute Management of Ischemic Strokes: JACC Focus Seminar

Acute ischemic stroke is the leading cause of disability and among the leading causes of mortality worldwide. Intravenous tissue plasminogen activator has been a cornerstone for treatment of acute ischemic stroke for more than 20 years; however, its use is limited due to a narrow therapeutic window, several contraindications, and low efficacy to recanalize the artery in large vessel occlusion. Recently, the addition of endovascular mechanical thrombectomy of large artery occlusion has revolutionized the stroke treatment for most disabling strokes. The paper reviews updates to the thrombolytic treatment as well as catheter-based treatment, and results from recent trials in the selection of patients in an extended time window using perfusion imaging.     

Red Yeast Rice for Hypercholesterolemia: JACC Focus Seminar

The extracts of red yeast rice (RYR) are currently the most effective cholesterol-lowering nutraceuticals. This activity is mainly due to monacolin K, a weak reversible inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, whose daily consumption causes a reduction in low-density lipoprotein (LDL)-cholesterol plasma levels up to 15% to 25% within 6 to 8 weeks. The decrease in LDL-cholesterol is accompanied by a proportional decrease in total and non–high-density lipoprotein cholesterol, plasma apolipoprotein B, and high-sensitivity C-reactive protein. Some trials suggest that RYR use is associated with improvement in endothelial function and arterial stiffness, whereas a long-term study supports its role in the prevention of cardiovascular events. Despite the statin-like mechanism of action, the risk related to 3 to 10 mg monacolin K taken per day is minimal (mild myalgia in previously severely statin-intolerant subjects). RYR could represent a therapeutic tool to support lifestyle improvement in managing mild to moderate hypercholesterolemia in low-risk patients, including those who cannot be treated with statins or other LDL-cholesterol–lowering therapies.     

The Contextualized Genetics of Human Longevity: JACC Focus Seminar

The genetics of human longevity has long been studied, and in this regard, centenarians represent a very informative model. Centenarians are characterized by 2 main features: 1) the capability to avoid or postpone the major age-related diseases; and 2) a high level of heterogeneity of their phenotype. The first suggests that longevity and resistance to diseases are mediated by shared mechanisms, the latter that many strategies can be used to become long lived, likely as a result of variable genome-environment interactions. The authors suggest that the complexity of genome-environment interactions must be considered within an evolutionary and ecological perspective and that the concept of “risk allele” is highly context dependent, changing with age, time, and geography. Genes involved in both longevity and cardiovascular diseases, taken as a paradigmatic example of age-related diseases, as well as other emerging topics in genetics of longevity, such as micro–ribonucleic acid (miRNA) genetics, polygenic risk scores, environmental pollutants, and somatic mutations are discussed.     

Takayasu Arteritis: JACC Focus Seminar 3/4

Takayasu arteritis is a rare idiopathic large-vessel vasculitis that typically affects young women. An early "prepulseless" stage is often missed, associated with nonspecific constitutional symptoms (fever, malaise, and weight loss) and elevated inflammatory markers. Unchecked disease progression leads to the "pulseless" stage, manifest clinically by missing pulses, vascular tenderness, and ischemic symptoms (limb claudication, dizziness, angina, and renovascular hypertension), and is characterized pathologically by arterial wall thickening and stenotic/occlusive lesions or aneurysm formation. Vascular complications (stroke, blindness, heart failure, and aneurysm rupture) could follow unless disease progression is halted by immunosuppressive therapy and critical lesions are palliated by timely endovascular therapy or open surgery. Early diagnosis, effective therapy, and lifelong surveillance for disease activity relapses and vascular disease progression are critical to successful long-term outcomes. The outlook for patients has improved significantly in recent years with the establishment of diagnostic and classification criteria, better investigational modalities, and more effective medical and invasive therapy.     

Nutritional Heart Disease and Cardiomyopathies: JACC Focus Seminar 4/4

This JACC Focus Seminar provides an overview of and highlights recently published research on cardiomyopathies and nutritional heart disease that have a higher prevalence in tropical regions. The development of tropical cardiomyopathies and nutritional cardiovascular disease (CVD) is complicated by high rates of poverty, fragmented health care systems, and suboptimal access to health care because of socioeconomic inequalities, leading to the fact that children, adolescents, and young adults are disproportionally affected. Such tropical cardiomyopathies and nutritional CVD that have not been prevalent in high-income countries in the past decades are now reemerging. When treating migrants or refugees, it is important for attending physicians to consider the burden of endemic diseases in the countries of origin and the likelihood that such patients might be affected. In this review, the authors propose an approach for adequate diagnostic work-up leading to appropriate care for those with suspected or confirmed tropical cardiomyopathies and nutritional CVD.     

Infections and Cardiovascular Disease: JACC Focus Seminar 1/4

The burden of cardiovascular diseases is sharply rising in low- and middle-income countries (LMICs). Along with the increasing rates of cardiovascular risk factors in these regions, there is a growing recognition of the contribution of neglected tropical diseases and other infections. Several cardiac implications of these infections have been reported but have not yet been validated by robust population data. This is in part due to limited access to health care and insufficient data collection infrastructure in many LMICs. Therefore, the true impact of these infections on the cardiovascular system may be underestimated, because of both underdiagnosis and underreporting bias. There is an urgent need to thoroughly delineate the cardiac impact of these conditions with elevated prevalence in LMICs and to propose strategies to reduce the negative consequences of these diseases in health systems with limited resources.     

Biological Versus Chronological Aging: JACC Focus Seminar

Aging is the main risk factor for vascular disease and ensuing cardiovascular and cerebrovascular events, the leading causes of death worldwide. In a progressively aging population, it is essential to develop early-life biomarkers that efficiently identify individuals who are at high risk of developing accelerated vascular damage, with the ultimate goal of improving primary prevention and reducing the health care and socioeconomic impact of age-related cardiovascular disease. Studies in experimental models and humans have identified 9 highly interconnected hallmark processes driving mammalian aging. However, strategies to extend health span and life span require understanding of interindividual differences in age-dependent functional decline, known as biological aging. This review summarizes the current knowledge on biological age biomarkers, factors influencing biological aging, and antiaging interventions, with a focus on vascular aspects of the aging process and its cardiovascular disease related manifestations.     

Coenzyme Q10 for Patients With Cardiovascular Disease: JACC Focus Seminar

Coenzyme Q₁₀ (CoQ₁₀) is a naturally occurring compound that is found in animals and all humans. It has a fundamental role in cellular energy production. Although it is produced in the body, tissue deficiency can occur due to medications such as statins, which inhibit the mevalonate pathway. The clinical syndromes of statin-associated muscle symptoms (SAMS) and some of the features observed in patients with heart failure (HF) may be related to blood and tissue deficiency of CoQ₁₀. Numerous clinical trials of CoQ₁₀ in SAMS have yielded conflicting results. Yet, the weight of evidence as reflected in meta-analyses supports the use of exogenous CoQ₁₀ in SAMS. In patients with HF, large-scale randomized clinical trials are lacking, although one relatively contemporary trial, Q-SYMBIO, suggests an adjunctive role for CoQ₁₀. The possibility that statin-related CoQ₁₀ deficiency may play a role in patients with diastolic HF is an intriguing hypothesis that warrants further exploration.     

Framingham Heart Study: JACC Focus Seminar, 1/8

The Framingham Heart Study is the longest-running cardiovascular epidemiological study, starting in 1948. This paper gives an overview of the various cohorts, collected data, and most important research findings to date. In brief, the Framingham Heart Study, funded by the National Institutes of Health and managed by Boston University, spans 3 generations of well phenotyped White persons and 2 cohorts comprised of racial and ethnic minority groups. These cohorts are densely phenotyped, with extensive longitudinal follow-up, and they continue to provide us with important information on human cardiovascular and noncardiovascular physiology over the lifespan, as well as to identify major risk factors for cardiovascular disease. This paper also summarizes some of the more recent progress in molecular epidemiology and discusses the future of the study.     

Alzheimer’s Disease and Vascular Aging: JACC Focus Seminar

Alzheimer’s disease, the leading cause of dementia in the elderly, is a neurodegenerative condition characterized by accumulation of amyloid plaques and neurofibrillary tangles in the brain. However, age-related vascular changes accompany or even precede the development of Alzheimer’s pathology, raising the possibility that they may have a pathogenic role. This review provides an appraisal of the alterations in cerebral and systemic vasculature, the heart, and hemostasis that occur in Alzheimer’s disease and their relationships to cognitive impairment. Although the molecular pathogenesis of these alterations remains to be defined, amyloid-β is a likely contributor in the brain as in the heart. Collectively, the evidence suggests that vascular pathology is a likely pathogenic contributor to age-related dementia, including Alzheimer’s disease, inextricably linked to disease onset and progression. Consequently, the contribution of vascular factors should be considered in preventive, diagnostic, and therapeutic approaches to address one of the major health challenges of our time.     

Multi-Ethnic Study of Atherosclerosis (MESA): JACC Focus Seminar 5/8

The MESA (Multi-Ethnic Study of Atherosclerosis) is a National Heart, Lung, and Blood Institute–sponsored prospective study aimed at studying the prevalence, progression, determinants, and prognostic significance of subclinical cardiovascular disease in a sex-balanced, multiethnic, community-dwelling U.S. cohort. MESA helped usher in an era of noninvasive evaluation of subclinical atherosclerosis presence, burden, and progression for the evaluation of atherosclerotic cardiovascular disease risk, beyond what could be predicted by traditional risk factors alone. Concepts developed in MESA have informed international patient care guidelines, providing new tools to effectively guide public health policy, population screening, and clinical decision-making. MESA is grounded in an open science model that continues to be a beacon for collaborative science. In this review, we detail the original goals of MESA, and describe how the scope of MESA has evolved over time. We highlight 10 significant MESA contributions to cardiovascular medicine, and chart the path forward for MESA in the year 2021 and beyond.     

Precision Medicine Approaches to Cardiac Arrhythmias: JACC Focus Seminar 4/5

In the initial 3 papers in this Focus Seminar series, the fundamentals and key concepts of precision medicine were reviewed, followed by a focus on precision medicine in the context of vascular disease and cardiomyopathy. For the remaining 2 papers, we focus on precision medicine in the context of arrhythmias. Specifically, in this fourth paper we focus on long QT syndrome, Brugada syndrome, and atrial fibrillation. The final (fifth) paper will deal with catecholaminergic polymorphic ventricular tachycardia. These arrhythmias represent a spectrum of disease ranging from common to relatively rare, with very different genetic and environmental causative factors, and with differing clinical manifestations that range from almost no consequences to lethality in childhood or adolescence if untreated. Accordingly, the emerging precision medicine approaches to these arrhythmias vary significantly, but several common themes include increased use of genetic testing, avoidance of triggers, and personalized risk stratification to guide the use of arrhythmia-specific therapies.     

Rheumatic Heart Disease: JACC Focus Seminar 2/4

It is a sad reality that although eminently preventable, and despite possessing such knowledge for >70 years, rheumatic heart disease (RHD) remains the most common cause of cardiovascular morbidity and early mortality in young people worldwide. A disease of the poor, RHD is one of the most neglected diseases. Several challenges are unique to the acute rheumatic fever/RHD continuum and contribute to its persistence, including its sequestration among the poorest, its protracted natural history, the erratic availability of penicillin, and the lack of a concerted effort in endemic regions. However, there is cause for optimism following a resurgence in scientific interest over the last 15 years. This review presents the latest advancements in epidemiology, diagnosis, and management. It also discusses pressing research questions on disease pathophysiology, the barriers to implementation of effective management strategies, and pragmatic policy solutions required for translation of current knowledge into meaningful action.     

Contraception and Reproductive Planning for Women With Cardiovascular Disease: JACC Focus Seminar 5/5

The majority of reproductive-age women with cardiovascular disease are sexually active. Early and accurate counseling by the cardiovascular team regarding disease-specific contraceptive safety and effectiveness is imperative to preventing unplanned pregnancies in this high-risk group of patients. This document, the final of a 5-part series, provides evidence-based recommendations regarding contraceptive options for women with, or at high risk for, cardiovascular disease as well as recommendations regarding pregnancy termination for women at excessive cardiovascular mortality risk due to pregnancy.     

Vitamin D,Calcium Supplements,and Implications for Cardiovascular Health: JACC Focus Seminar

Vitamin D and calcium supplements are commonly used, often together, to optimize bone health. Multiple observational studies have linked low serum 25-hydroxyvitamin D concentrations with increased cardiovascular risk. However, subsequent randomized controlled trials (RCTs) failed to demonstrate cardiovascular benefit with vitamin D supplementation. Although vitamin D supplements do not appear to be harmful for cardiovascular health, the lack of benefit in RCTs should discourage their use for this purpose, favoring optimizing vitamin D status through healthy lifestyles such as specific foods and modest sunlight exposure. Furthermore, some (but not all) observational and RCT studies of calcium supplementation have suggested potential for cardiovascular harm. Therefore, calcium supplementation should be used cautiously, striving for recommended intake of calcium predominantly from food sources. In this review, the authors examine the currently available evidence investigating whether vitamin D and calcium supplements are helpful, harmful, or neutral for cardiovascular health.