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Coronary Heart Disease: Clinical, Pathological, Imaging, and Molecular Profiles presents a comprehensive picture of ischemic heart disease for practitioners, students, and investigators dealing with the varied facets of this complex subject. Individual chapters introduce the anatomy of the coronary blood vessels and cardiac development, while others consider current imaging modalities utilized for ischemic heart disease, including stress echo, nuclear diagnostic tests, non-invasive coronary artery imaging, and coronary angiography. Imaging chapters provide key clinical information on techniques and indications, and include examples of both normal and abnormal patterns.

The principle thrust of the book concerns coronary atherosclerosis, the pathology of which is presented in conjunction with the results of anatomic, non-invasive imaging and angiographic studies. Related chapters cover atherogenesis, presenting new insights into the pathophysiology of the vulnerable plaque, the role of progenitor cells in vascular injury, inflammation and atherogenesis, and the genomics of vascular remodeling. Additional topics covered include angina pectoris, acute coronary syndromes, healed myocardial infarction and congestive heart failure, catheter-based and surgical revascularization, and surgical treatment of myocardial infarction and its sequelae.

With contributions from a diverse group of internationally-known physicians with broad experience in the diagnosis and treatment of coronary heart disease, this book will be a valuable resource for practitioners in clinical cardiology, thoracic surgery, pathology, and cardiovascular molecular research, as well as for students in training.



Chapter 1. Anatomy of Coronary Vessels

This chapter presents a description and illustration of the anatomic features of the coronary vessels. It first deals with the typical course and important variations of each major artery and then with anatomy of the veins, both as seen anatomically and in imaging, pairing coronary arteriograms and CT angiograms. Understanding coronary vessels’ anatomy is foundational for the diagnosis and treatment of ischemic heart disease.
Zeev Vlodaver, John R. Lesser

Chapter 2. Cardiac Development and Congenital Heart Disease

The heart is a dynamic organ that pumps more than two billion beats in the average lifetime. It is the first organ to develop during embryogenesis and requires a complex interaction of signaling factors, transcriptional networks, and microRNAs to regulate discrete stages of cardiac specification, differentiation, chamber formation, and growth. Spontaneous genetic mutations in humans and engineered molecular mutations in model systems have improved our understanding of cardiac development in both the human and nonprimate heart. While congenital heart disease (CHD) is relatively common and can be life-threatening, emerging therapies including catheter-based interventions, surgical repair, cellular repair, and cell therapy are improving survival and resulting in increased numbers of adults living with heart disease. Better understanding the mechanisms that govern cardiac development can clarify the pathology of CHD and help develop new therapies for this patient population.
Jamie L. Lohr, Cindy M. Martin, Daniel J. Garry

Chapter 3. Echocardiographic Evaluation of Ischemic Heart Disease

State-of-the-art echo-Doppler is the most practical and useful technique for rapid, noninvasive bedside evaluation of coronary heart disease. This chapter highlights changes in technology over the past 40 years that have advanced the status of echo-Doppler techniques in the evaluation of coronary heart disease. It emphasizes echo-Doppler’s use in diagnosing myocardial infarction and its complications, its prognostic value, and ability to guide specific treatment. The role of echo-Doppler in diagnosing coronary heart disease using exercise or pharmacologic stress technique is also reviewed.
Richard W. Asinger, Fouad A. Bachour, Gautam R. Shroff

Chapter 4. Nuclear Imaging in Ischemic Heart Disease

Ischemic heart disease is one of the major causes of mortality and morbidity in men and women accounting for 34.3% (1 of every 2.9) deaths in the US in 2006 [1]. Noninvasive imaging techniques of echocardiography, nuclear imaging, cardiac CT, and cardiac magnetic resonance imaging have played a major role in the evaluation and management of patients with ischemic heart disease. This chapter will focus on the role of nuclear imaging techniques in the evaluation of ischemic heart disease. We will discuss the clinical applications of the most commonly used nuclear imaging techniques of single-photon emission computed tomography (SPECT) and positron emission tomography (PET) in the evaluation of patients with known or suspected stable coronary artery disease (CAD), acute chest pain and acute coronary syndromes (ACS) (NSTEMI and STEMI), and chronic heart failure.
Sharmila Dorbala, Marcelo F. Di Carli

Chapter 5. Noninvasive Coronary Artery Imaging with CT and MRI

Cardiac CT angiography (CCTA) for coronary artery evaluation is now a clinically useful modality as a result of concurrent developments in computer speed and memory, and powerful multidetector CT scanner hardware with post-processing software. For many years, invasive coronary angiography was the gold standard for evaluating coronary artery disease since it provides a clear view of the coronary artery. But, it comes with a small risk of associated morbidity. Noninvasive coronary artery evaluation previously relied on phenomena secondary to coronary stenosis during physiologic stress (electrocardiogram, wall motion, and perfusion changes), but multiple problems with test performance still limit sensitivity and specificity. CCTA of the coronary artery lumen and wall permits noninvasive visualization, prognosis assessment, and an ability to determine the potential source of symptoms. In this chapter, we review CCTA techniques, data supporting its clinical application, clinical uses, associated radiation exposure, and future directions.
Marc C. Newell, Robert S. Schwartz, John R. Lesser

Chapter 6. Catheter-Based Coronary Angiography

The primary goal of catheter-based coronary angiography is the identification, localization, and assessment of stenotic lesions present within the coronary arteries that will enable us to determine the pathophysiologic significance of the obstructive lesions in question regarding ischemia vs. nonischemia.
This chapter presents a description and illustration of the use of catheter-based coronary angiography. First, it deals with technical aspects, vascular access, and early recognition of complications that may occur with this procedure and its prevention. Also, it illustrates angiographic patterns of collateral circulation associated with severe obstructive coronary disease.
The use of catheter-based coronary angiography provides significant information that is important for the management of the individual patient with and without ischemic heart disease.
Robert F. Wilson, Zeev Vlodaver

Chapter 7. Coronary Artery Anomalies

Anomalous coronary arteries are a heterogeneous group of disorders which vary in clinical importance from benign to highly malignant, causing angina, syncope, or sudden death. They are the second-most-common cause of sudden cardiac death in young athletes. The interarterial artery, located between the aorta and pulmonary artery, is the most concerning type, especially for patients with an anomalous left coronary artery. The treatment approach depends on hemodynamic significance, symptoms, and high-risk features. New imaging modalities, including coronary computed tomography angiography, may be helpful in determining the optimal therapeutic approach.
Thomas Knickelbine, Michael Bolooki, Zeev Vlodaver

Chapter 8. Pathology of Chronic Obstructive Coronary Disease

This chapter focuses on pathology of coronary atherosclerosis as well as on the various types of lesions of the coronary ostia.
Intrinsic disease of the coronary arteries is overwhelmingly atherosclerotic in nature. Uncommon forms of significant coronary disease include ostial stenosis from primary disease of the aorta.
Lesions generally classified as coronary atherosclerosis are focal, often eccentric thickenings of the intima with fibrous tissue and accumulation of lipid-laded macrophages foam cells. Characteristically, the purely atheromatous lesion is associated with a residual lumen. With such a lesion, the artery may be termed obstructed or stenotic. Complicating lesions include thrombi and intramural hemorrhage. In instances of chronic ischemic heart disease, coronary thrombi are found to be organized and represented by foci of vascular connective tissue obstructing a lumen previously narrowed by underlying atherosclerosis. Arteries so involved may be said to be occluded.
Zeev Vlodaver

Chapter 9. Vulnerable Plaque

Despite continuing advances in medical therapies, diagnostic imaging modalities, and other refinements in basic or translational research, atheromatous coronary artery disease remains a major cause of morbidity and mortality throughout the world. Because atherosclerosis is a complex, multifactorial disease, it is essential to have a comprehensive understanding of morphology and critical pathological processes involved in atheroma formation. This chapter focuses on key histopathological features of vulnerable plaques and their association with predecessor lesions of atherosclerosis progression from early to late stages. It also describes the underlying mechanisms associated with each lesion type.
Masataka Nakano, Frank D. Kolodgie, Fumiyuki Otsuka, Saami K. Yazdani, Elena R. Ladich, Renu Virmani

Chapter 10. Genetics and Coronary Heart Disease

Coronary heart disease (CHD) is the single leading cause of death in America, accounting for about one of every five deaths [1]. Family history of premature parental CHD is associated with a twofold increased risk of cardiovascular disease, making it vital that providers know their patients’ histories. For patients who do not know their family history, genetic testing is being considered as a means to someday fill this gap and will also increase the focus on prevention, provide better diagnostics, and help direct treatment options. This chapter summarizes findings about genes associated with CHD and raises practical and ethical issues that need to be addressed as this field of genetics evolves and before genetic testing at clinics becomes commonplace.
Jennifer L. Hall, Ryan J. Palacio, Eric M. Meslin

Chapter 11. Endothelium Biology

The endothelium lines the blood vessels of arteries, veins, and lymphatics. In the cardiovascular system, it plays a vital role in multiple functions ranging from control of vascular tone to repair after injury. This chapter focuses on endothelium biology, specifically that of the coronary tree, and its translational implications. It describes how the endothelium becomes dysfunctional during coronary artery disease and how this dysfunction can be measured and treated.
Michael Sean McMurtry, Evangelos D. Michelakis

Chapter 12. Stem Cells and Atherosclerosis

Many factors contribute to the development of atherosclerosis, including endothelial dysfunction. Research shows that certain types of circulating stem cells and progenitor cells may counteract the development of atherosclerosis following vessel injury and promote vascular health. Yet other studies indicate that these same cells may be involved in the disease’s progression. In this chapter, we sort through these findings and examine the limitations of research to date in order to better understand the role of endothelial progenitor cells and smooth muscle progenitor cells in atherosclerosis and plaque rupture.
Jay H. Traverse

Chapter 13. Induced Pluripotential Stem Cells and the Prospects for Cardiac Cell Therapy

This chapter explains the properties of induced pluripotential stem cells (iPS cells) and why they may represent a new dawn for cell therapy of the heart. iPS cells are very similar to embryonic stem cells (ES cells) in that they can grow without limit in tissue culture, and can form all of the cell types in the normal body. But unlike embryonic stem cells, their production requires no eggs or embryos, and can probably be achieved from any individual patient. The technology of making and using iPS cells is based entirely on knowledge gained from growing ES cells. Because ES cells represent the gold standard in performance, it is important to understand their nature and properties as background for understanding and maximizing the potential of iPS cells.
Jonathan M. W. Slack, James R. Dutton

Chapter 14. Regulation of Vasculogenesis and Angiogenesis

This chapter covers the two major processes involved in the development of blood vessels in embryos and adults: vasculogenesis and angiogenesis, respectively. Vasculogenesis refers to the de novo formation of blood vessels from endothelial progenitors or angioblasts and was believed to be restricted to embryogenesis. The dogma that postnatal neovascularization resulted exclusively from angiogenesis – the proliferation, migration, and remodeling from preexisting blood vessels – was challenged in 1997 with the identification of adult circulating endothelial progenitor cells (EPCs). These findings have important implications not only for a better understanding of the vascular system but also for regenerative medicine since these circulating endothelial progenitors could potentially be useful in the treatment of ischemic conditions.
Rita C. R. Perlingeiro

Chapter 15. Chronic Stable Angina

Millions live with chronic stable angina. Incidence is likely to grow as the population ages and as risk factors increase. Similarly, treatment options are expanding. Medical therapies from drug regimens to percutaneous coronary intervention and coronary artery bypass grafts are significantly reducing morbidity and mortality, with additional experimental therapies on the horizon. This chapter describes these therapies as well as how stable angina is diagnosed and prognosis determined. It also presents the results of multiple clinical studies that evaluated treatment options for improving symptoms and prolonging life. Clinical data help clarify whether optimal medical therapy or revascularization is the better option for individual patients.
Santiago Garcia, Edward O. McFalls

Chapter 16. Pathology of Sudden Death in Coronary Arterial Diseases

Most cases of sudden unexpected death are cardiac in nature, and the majority are related to coronary artery disease. While atherosclerotic coronary artery disease is the most common cause of sudden unexpected death in the United States, nonatherosclerotic coronary artery diseases are an important cause of sudden unexpected death, especially in the young. This chapter describes causes of sudden death related to both categories of coronary artery disease.
Shannon M. Mackey-Bojack, Emily R. Duncanson, Susan J. Roe

Chapter 17. Acute Coronary Syndromes

Coronary syndromes that cause a relatively rapid onset or increase of symptoms or ischemia are termed acute coronary syndromes (ACSs). ACS is a continuum of unstable coronary syndromes that stretches from “unstable angina” to acute ST-segment myocardial infarction (STEMI). In this chapter, we will discuss the portion of the spectrum that extends from unstable angina to minor non-ST-segment myocardial infarction (NSTEMI). STEMI and related syndromes are discussed in Chap. 18.
The hallmark of ACSs is a fairly abrupt onset of angina (or equivalent ischemic symptoms, such as dyspnea and diaphoresis) or rapid worsening of preexisting ischemic cardiac symptoms. For more than a century, this change in clinical symptoms has been associated with a high risk of subsequent myocardial infarction or cardiac death (Lancet 1:860, 1972). The syndrome has also been termed crescendo angina, preinfarction angina, and unstable angina, all connoting its ominous natural history.
Robert F. Wilson

Chapter 18. Complications of Acute Myocardial Infarction

This chapter describes and illustrates complications of acute myocardial infarction, including mechanical, arrhythmic, and embolic disturbances. Circulatory failure from severe left ventricular dysfunction or other mechanical complications of acute myocardial infarction accounts for most fatalities. Mechanical complications include left ventricular failure with cardiogenic shock, cardiac free wall rupture, ventricular septal rupture, papillary muscle rupture, and right ventricular failure.
Zeev Vlodaver, Robert F. Wilson

Chapter 19. Healed Myocardial Infarction

Among the many devastating complications of healed myocardial infarction is heart failure (HF). Despite its ubiquitous role in causing death and disability around the globe, HF is quite difficult to define. It has a great deal of heterogeneity, can be acute or chronic, may involve primarily the left ventricle or right ventricle (or both), can be associated with a low or normal left ventricular ejection fraction (LVEF), and has numerous causes. This chapter focuses on HF due to chronic coronary artery disease (CAD).
Virtually any form of heart disease can lead to heart failure. In general, HF is a clinical syndrome caused by structural and/or functional changes in the heart that lead to dyspnea, fatigue, and in many cases, salt and water retention. Comorbidities such as CAD, hypertension, diabetes mellitus, chronic kidney disease, or atrial fibrillation frequently accompany HF, and may contribute to or aggravate the HF syndrome.
In the end, patients typically become gradually more and more disabled and eventually die prematurely from pump dysfunction or arrhythmia. Improvement in therapy the past 30 years has improved survival, but HF continues to exact a toll on patients, their families, and the worldwide economy.
Gary S. Francis, Daniel J. Garry

Chapter 20. Nonatherosclerotic Ischemic Heart Disease

Atherosclerosis predominates as the pathologic lesion in coronary artery disease. Less commonly, other nonatherosclerotic etiologic processes involve the coronary arteries, with or without symptoms. This chapter explores the nonatherosclerotic etiologies of coronary artery disease, from spontaneous and device-induced vasospasm to spontaneous coronary artery dissection, vasculitis, embolism, aneurysm, and microcirculatory coronary disease to the impact of chest irradiation, heart valve transplants, congenital conditions, and cocaine use.
Uma S. Valeti, Robert F. Wilson, Zeev Vlodaver

Chapter 21. Transcatheter Treatment of Coronary Artery Disease

This chapter describes the various methods of percutaneous coronary intervention (PCI), including balloon angioplasty, stenting, thrombectomy, and atherectomy, and the application of intravascular ultrasound. It also illustrates the use of PCI in special cases, as in acute coronary syndromes, acute myocardial infarction, chronic total occlusion, severe calcification of the coronary arteries, and aneurysmal disease. PCI is now the primary method of coronary revascularization. PCI originated as balloon angioplasty, first performed in humans by Andreas Gruntzig in 1978, but it has evolved into a variety of catheter-based methods to treat coronary disease [1]. PCI has revolutionized modern cardiovascular care, enabling patients with myocardial ischemia to be treated less invasively by avoiding a surgical approach. As experience accrued and the technology advanced, the number of patients and angiographic lesion subsets increased dramatically – up to the current era in which PCI is now more commonly performed than coronary artery bypass graft (CABG) surgery. When available and performed in experienced centers by well-trained, expert physicians and teams, it has become the procedure of choice for acute coronary syndromes, acute myocardial infarction, single-vessel coronary artery disease, and many patients with two- and three-vessel coronary artery disease. In addition, it has become the treatment of choice for saphenous vein bypass graft stenoses.
Robert F. Wilson

Chapter 22. Surgical Treatment of Coronary Artery Disease

Development of coronary angiogram by Sones at the Cleveland Clinic during the early 1960s made possible precise ­identification of anatomical coronary artery disease and laid foundation for modern coronary artery surgery [1]. In 1967 Favaloro at the Cleveland Clinic began performing coronary artery bypass grafting (CABG) with reversed vein grafts [2]. In 1968 Green et al. [3] at New York University used a dissecting microscope to perform anastomosis of the internal mammary artery (IMA) to the left anterior descending artery (LAD). Largely overlooked by the western world is the first CABG, in which an IMA was anastomozed to the LAD, was performed by Russian surgeon Kolessov [4] prior to 1967.
Kenneth Liao

Chapter 23. Noncoronary Surgical Therapy for Ischemic Heart Disease

Mechanical complications of coronary artery disease are rare but frequently lead to fatal outcomes. Saving critically ill patients may be possible with optimal timing of surgical intervention. While selecting the most appropriate patients for these life-saving therapies is difficult in the acuity of the moment, certain perioperative variables can guide clinicians’ decision-making.
Christopher B. Komanapalli, Balaji Krishnan, Ranjit John

Chapter 24. Refractory Angina

A growing number of patients have refractory angina – but limited therapeutic options. Revascularization, medical therapy, and risk factor modification have improved notably, but these patients are left with severe limitations in their quality of life. As described in this chapter, an increasing number of pharmacologic and nonpharmacologic approaches for “no-option patients” are making quality-of-life inroads for this challenging patient population.
Mohammad Sarraf, Daniel J. Hellrung, Timothy D. Henry

Chapter 25. Acute Catheter-Based Mechanical Circulatory Support

Procedural and technology-based advances in circulatory support have enabled an increased number of patients to receive percutaneous coronary intervention (PCI). Without these advances, many patients would not have been considered for the procedure because of their elevated risk for complications. This chapter describes transcatheter-based circulatory support devices in clinical use today as well as data that support their usage and suggested protocols.
Gladwin S. Das, Ganesh Raveendran, Jason C. Schultz

Chapter 26. Surgical Mechanical Circulatory Support

A significant and increasing number of Americans develop heart failure, and many die from the disease. Improved medical therapies are slowing its progression, but patients with advanced heart failure face limited options. This chapter explores treatment options for patients with advanced heart failure, focusing on mechanical circulatory support – categories, capabilities, indications, complications, and future direction.
Forum Kamdar, Ranjit John

Chapter 27. Diabetes and Coronary Heart Disease

Cardiovascular disease is the leading cause of death among patients with diabetes. Hyperglycemia, hypertension, and dyslipidemia associated with type 2 diabetes each contribute to the accelerated atherosclerosis that occurs in this disease. An integrated approach to diabetes management can halve the rate of cardiovascular events through lifestyle modification, smoking cessation, use of antiplatelet drugs, and careful attention to management of glucose, blood pressure, and dyslipidemia. While challenging to accomplish, thoughtful management can meaningfully improve both the quality of life and longevity of patients with diabetes.
Graham T. McMahon

Chapter 28. Cardiovascular Disease in Women

Cardiovascular disease (CVD) is the leading cause of death in women of all age. An understanding of CVD in women is critical, especially given the aging population and the growing incidence of obesity, diabetes, and metabolic syndrome in our society. This chapter covers gender differences in risk factors for CVD, symptom presentation, and disease progression, as well as implications for diagnosis and treatment.
Margo Tolins-Mejia

Chapter 29. Prevention of Coronary Artery Disease

Many cardiovascular risk factors are involved in the development of coronary artery disease (CAD). Evidence-based medicine has taught us that lifestyle modifications such as a heart-healthy diet, smoking cessation, daily exercise, and optimal weight control have a significant impact on reducing cardiovascular morbidity and mortality. This chapter discusses these interventions as well as the role of antihypertensive, antiplatelet, and cholesterol-lowering therapies.
Despite the enormous progress in primary and secondary CAD prevention in the past few decades, the residual risk is still important, and therefore, continuous intensive research is mandatory in this field. Joint National Committee (JNC) VIII and Adult Treatment Panel (ATP) IV will guide us for the next decade in better qualitative and quantitative approaches for the preventive management of CAD.
Daniel Duprez

Chapter 30. Innovations in Twenty-First Century Cardiovascular Medicine

Emerging technologies are revolutionizing therapies for patients with end-stage heart disease. While these technologies improve the quality of life for our patients, continued efforts are needed to develop curative and preventive therapies for this pervasive disease. A frequently cited quote from C. Walton Lillehei, MD, provides hope for our future, “What mankind can dream, research and technology can achieve.”
Heart disease is both common and deadly. Today, heart disease is the number one cause of death in the United States and worldwide (Circulation 121:e46–215, 2010). Estimates suggest that the US economy will direct approximately $475 billion to treating heart disease and that these expenses are predicted to continue to grow at a seismic pace (Circulation 119:480–6, 2009). Our families, neighbors, coworkers, and communities are profoundly impacted by this disease, as one US citizen dies from cardiovascular disease every 30 s. The only way to profoundly alter the course of this disease is through innovation and the development of new therapies.
Mary G. Garry, Joseph M. Metzger, Xiaozhong Shi, Daniel J. Garry


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