CV 231 PDF: Disorders of the Cardiovascular System

Disorders of the Cardiovascular System PART 6 punctuated by episodes of acute deterioration only late in the course of Section 1 Introduction to Cardiovascular...

Disorders of the Cardiovascular System PART 6 punctuated by episodes of acute deterioration only late in the course of Section 1 Introduction to Cardiovascular the disease. Understanding the natural history of various cardiac dis- Disorders orders is essential for applying appropriate diagnostic and therapeutic measures to each stage of the condition, as well as for providing the patient and family with the likely prognosis. 231 Approach to the Patient with Possible Cardiovascular CARDIAC SYMPTOMS The symptoms caused by heart disease result most commonly from myocardial ischemia, disturbance of the contraction and/or relaxation Disease of the myocardium, obstruction to blood flow, or an abnormal cardiac rhythm or rate. Ischemia, which is caused by an imbalance between the Joseph Loscalzo heart’s oxygen supply and demand, is manifest most frequently as chest discomfort (Chap. 11), whereas reduction of the pumping ability of the heart commonly leads to fatigue and elevated intravascular pressure upstream of the failing ventricle. The latter results in abnormal fluid THE MAGNITUDE OF THE PROBLEM accumulation, with peripheral edema (Chap. 37) or pulmonary conges- Cardiovascular diseases comprise the most prevalent serious disorders tion and dyspnea (Chap. 33). Obstruction to blood flow, as occurs in in industrialized nations and are a rapidly growing problem in devel- valvular stenosis, can cause symptoms resembling those of myocardial oping nations (Chap. 233). Age-adjusted death rates for coronary heart failure (Chap. 252). Cardiac arrhythmias often develop suddenly, and disease have declined by two-thirds in the last four decades in the the resulting symptoms and signs—palpitations (Chap. 39), dyspnea, United States, reflecting the identification and reduction of risk factors hypotension, and syncope (Chap. 18)—generally occur abruptly and as well as improved treatments and interventions for the management may disappear as rapidly as they develop. of coronary artery disease, arrhythmias, and heart failure. Nonetheless, Although dyspnea, chest discomfort, edema, and syncope are car- cardiovascular diseases remain the most common causes of death, dinal manifestations of cardiac disease, they occur in other conditions responsible for 35% of all deaths, almost 1 million deaths each year. as well. Thus, dyspnea is observed in disorders as diverse as pulmo- Approximately one-fourth of these deaths are sudden. In addition, nary disease, marked obesity, and anxiety (Chap. 33). Similarly, chest cardiovascular diseases are highly prevalent, diagnosed in 80 million discomfort may result from a variety of noncardiac and cardiac causes adults, or ~35% of the adult population. The growing prevalence of other than myocardial ischemia (Chap. 11). Edema, an important find- obesity (Chap. 395), type 2 diabetes mellitus (Chap. 396), and metabolic ing in untreated or inadequately treated heart failure, also may occur syndrome (Chap. 401), which are important risk factors for atheroscle- with primary renal disease and in hepatic cirrhosis (Chap. 37). Syncope rosis, now threatens to reverse the progress that has been made in the occurs not only with serious cardiac arrhythmias but in a number age-adjusted reduction in the mortality rate of coronary heart disease. of neurologic conditions as well (Chap. 18). Whether heart disease For many years, cardiovascular disease was considered to be more is responsible for these symptoms frequently can be determined by common in men than in women. In fact, the percentage of all deaths carrying out a careful clinical examination (Chap. 234), supplemented secondary to cardiovascular disease is higher among women (43%) by noninvasive testing using electrocardiography at rest and during than among men (37%) (Chap. 391). In addition, although the absolute exercise (Chap. 235), echocardiography, roentgenography, and other number of deaths secondary to cardiovascular disease has declined forms of myocardial imaging (Chap. 236). over the past decades in men, this number has actually risen in women. Myocardial or coronary function that may be adequate at rest may Inflammation, obesity, type 2 diabetes mellitus, and the metabolic be insufficient during exertion. Thus, dyspnea and/or chest discom- syndrome appear to play more prominent roles in the development fort that appear during activity are characteristic of patients with of coronary atherosclerosis in women than in men. Coronary artery heart disease, whereas the opposite pattern, that is, the appearance of disease (CAD) is more frequently associated with dysfunction of the these symptoms at rest and their remission during exertion, is rarely coronary microcirculation in women than in men. Exercise electrocar- observed in such patients. It is important, therefore, to question the diography has a lower diagnostic accuracy in the prediction of epicar- patient carefully about the relation of symptoms to exertion. dial obstruction in women than in men. Many patients with cardiovascular disease may be asymptomatic NATURAL HISTORY both at rest and during exertion but may present with an abnormal Cardiovascular disorders often present acutely, as in a previously physical finding such as a heart murmur, elevated arterial pressure, asymptomatic person who develops an acute myocardial infarction or an abnormality of the electrocardiogram (ECG) or imaging test. It (Chap. 269), or a previously asymptomatic patient with hypertro- is important to assess the global risk of CAD in asymptomatic indi- phic cardiomyopathy (Chap. 254) or with a prolonged QT interval viduals, using a combination of clinical assessment and measurement (Chap. 247) whose first clinical manifestation is syncope or even sud- of cholesterol and its fractions, as well as other biomarkers, such as den death. However, the alert physician may recognize the patient at C-reactive protein, in some patients. Since the first clinical manifes- risk for these complications long before they occur and often can take tation of CAD may be catastrophic—sudden cardiac death, acute measures to prevent their occurrence. For example, a patient with myocardial infarction, or stroke in previous asymptomatic persons—it acute myocardial infarction will often have had risk factors for athero- is mandatory to identify those at high risk of such events and institute sclerosis for many years. Had these risk factors been recognized, their further testing and preventive measures. elimination or reduction might have delayed or even prevented the DIAGNOSIS infarction. Similarly, a patient with hypertrophic cardiomyopathy may As outlined by the New York Heart Association (NYHA), the elements have had a heart murmur for years and a family history of this disor- of a complete cardiac diagnosis include the systematic consideration der. These findings could have led to an echocardiographic examina- of the following: tion, recognition of the condition, and appropriate therapy long before the occurrence of a serious acute manifestation. 1. The underlying etiology. Is the disease congenital, hypertensive, Patients with valvular heart disease or idiopathic dilated cardiomy- ischemic, or inflammatory in origin? opathy, by contrast, may have a prolonged course of gradually increas- 2. The anatomic abnormalities. Which chambers are involved? Are they ing dyspnea and other manifestations of chronic heart failure that is hypertrophied, dilated, or both? Which valves are affected? Are they Harrisons_20e_Part6_p1649-p1942.indd 1649 6/1/18 12:48 PM  1650 TABLE 231-1 New York Heart Association Functional Classification ASSESSMENT OF FUNCTIONAL IMPAIRMENT Class I Class III When an attempt is made to determine the severity of functional No limitation of physical Marked limitation of physical impairment in a patient with heart disease, it is helpful to ascertain activity activity the level of activity and the rate at which it is performed before No symptoms with ordinary Less than ordinary activity causes symptoms develop. Thus, it is not sufficient to state that the patient complains of dyspnea. The breathlessness that occurs after running PART 6 exertion symptoms Class II Asymptomatic at rest up two long flights of stairs denotes far less functional impairment Slight limitation of physical activity Class IV than do similar symptoms that occur after taking a few steps on level ground. In addition, the degree of customary physical activity at work Ordinary activity causes symptoms Inability to carry out any physical activity without discomfort and during recreation should be considered. The development of two- Disorders of the Cardiovascular System flight dyspnea in a well-conditioned marathon runner may be far more Symptoms at rest significant than the development of one-flight dyspnea in a previously Source: Data from The Criteria Committee of the New York Heart Association. sedentary person. The history should include a detailed consideration of the patient’s therapeutic regimen. For example, the persistence or regurgitant and/or stenotic? Is there pericardial involvement? Has development of edema, breathlessness, and other manifestations of there been a myocardial infarction? heart failure in a patient who is receiving optimal doses of diuretics and 3. The physiologic disturbances. Is an arrhythmia present? Is there other therapies for heart failure (Chap. 252) is far graver than are sim- evidence of congestive heart failure or myocardial ischemia? ilar manifestations in the absence of treatment. Similarly, the presence 4. Functional disability. How strenuous is the physical activity required to of angina pectoris despite treatment with optimal doses of multiple elicit symptoms? The classification provided by the NYHA has been antianginal drugs (Chap. 267) is more serious than it is in a patient on found to be useful in describing functional disability (Table 231-1). no therapy. In an effort to determine the progression of symptoms, and thus the severity of the underlying illness, it may be useful to ascertain One example may serve to illustrate the importance of establishing what, if any, specific tasks the patient could have carried out 6 months a complete diagnosis. In a patient who presents with exertional chest or 1 year earlier that he or she cannot carry out at present. discomfort, the identification of myocardial ischemia as the etiology is of great clinical importance. However, the simple recognition of ische- ELECTROCARDIOGRAM mia is insufficient to formulate a therapeutic strategy or prognosis until (See also Chap. 235) Although an ECG usually should be recorded in the underlying anatomic abnormalities responsible for the myocardial patients with known or suspected heart disease, with the exception of ischemia, for example, coronary atherosclerosis or aortic stenosis, are the identification of arrhythmias, conduction abnormalities, ventricular identified and a judgment is made about whether other physiologic hypertrophy, and acute myocardial infarction, it generally does not disturbances that cause an imbalance between myocardial oxygen sup- establish a specific diagnosis. The range of normal electrocardiographic ply and demand, such as severe anemia, thyrotoxicosis, or supraven- findings is wide, and the tracing can be affected significantly by many tricular tachycardia, play contributory roles. Finally, the severity of noncardiac factors, such as age, body habitus, and serum electrolyte the disability should govern the extent and tempo of the workup and concentrations. In general, electrocardiographic changes should be strongly influence the therapeutic strategy that is selected. interpreted in the context of other abnormal cardiovascular findings. The establishment of a correct and complete cardiac diagnosis usu- ally commences with the history and physical examination (Chap. 234). ASSESSMENT OF THE PATIENT WITH A HEART Indeed, the clinical examination remains the basis for the diagnosis MURMUR of a wide variety of disorders. The clinical examination may then be (Fig. 231-1) The cause of a heart murmur can often be readily supplemented by five types of laboratory tests: (1) ECG (Chap. 235), elucidated from a systematic evaluation of its major attributes: (2) noninvasive imaging examinations (chest roentgenogram, echoc- timing, duration, intensity, quality, frequency, configuration, location, ardiogram, radionuclide imaging, computed tomographic imaging, and radiation when considered in the light of the history, general positron emission tomography, and magnetic resonance imaging) (Chap. 236), (3) blood tests to assess risk (e.g., lipid determinations, C-reactive protein) or cardiac function (e.g., brain natriuretic peptide EVALUATION OF HEART MURMUR [BNP] [Chap. 252]), (4) occasionally specialized invasive examinations PRESENCE OF CARDIAC MURMUR (i.e., cardiac catheterization and coronary arteriography [Chap. 237]), and (5) genetic tests to identify monogenic cardiac diseases (e.g., hyper- Systolic Murmur Diastolic or trophic cardiomyopathy [Chap. 254], Marfan’s syndrome [Chap. 406], Continuous Murmur and abnormalities of cardiac ion channels that lead to prolongation of the QT interval and an increase in the risk of sudden death [Chap. 241]). These tests are becoming more widely available. Grade I + II Grade III or >, and midsystolic holosystolic, or late systolic FAMILY HISTORY In eliciting the history of a patient with known or suspected car- diovascular disease, particular attention should be directed to the Asymptomatic and Other signs or family history. Familial clustering is common in many forms of heart no associated findings symptoms of disease. Mendelian transmission of single-gene defects may occur, cardiac disease as in hypertrophic cardiomyopathy (Chap. 254), Marfan’s syndrome Echocardiography (Chap. 406), and sudden death associated with a prolonged QT syndrome (Chap. 247). Premature coronary disease and essential hypertension, Normal ECG and Abnormal ECG type 2 diabetes mellitus, and hyperlipidemia (the most important risk chest X-ray or chest X-ray factors for CAD) are usually polygenic disorders. Although familial transmission may be less obvious than in the monogenic disorders, it is No further Cardiac consult helpful in assessing risk and prognosis in polygenic disorders, as well. workup if appropriate Familial clustering of cardiovascular diseases not only may occur on a genetic basis but also may be related to familial dietary or behavior FIGURE 231-1 Approach to the evaluation of a heart murmur. ECG, patterns, such as excessive ingestion of salt or calories and cigarette electrocardiogram. (Reproduced with permission from Primary Cardiology, 2nd ed, smoking. E Braunwald, L Goldman [eds]. Philadelphia, Saunders, 2003.) Harrisons_20e_Part6_p1649-p1942.indd 1650 6/1/18 12:48 PM  physical examination, and other features of the cardiac examination, as intervals for repeated examinations. If there is no evidence of dis- 1651 described in Chap. 234. ease, such continued attention may lead to the patient’s developing The majority of heart murmurs are midsystolic and soft inappropriate concern about the possibility of heart disease. (grades I–II/VI). When such a murmur occurs in an asymptomatic 2. If there is no evidence of cardiovascular disease but the patient child or young adult without other evidence of heart disease on clinical has one or more risk factors for the development of ischemic heart CHAPTER 232 Basic Biology of the Cardiovascular System examination, it is usually benign and echocardiography generally is not disease (Chap. 267), a plan for their reduction should be developed required. By contrast, two-dimensional and Doppler echocardiography and the patient should be retested at intervals to assess compliance (Chap. 236) are indicated in patients with loud systolic murmurs and efficacy in risk reduction. (grades ≥III/VI), especially those that are holosystolic or late systolic, 3. Asymptomatic or mildly symptomatic patients with valvular heart and in most patients with diastolic or continuous murmurs. disease that is anatomically severe should be evaluated periodically, every 6 to 12 months, by clinical and noninvasive examinations. PITFALLS IN CARDIOVASCULAR MEDICINE Early signs of deterioration of ventricular function may signify the Increasing subspecialization in internal medicine and the perfection need for surgical treatment before the development of disabling of advanced diagnostic techniques in cardiology can lead to several symptoms, irreversible myocardial damage, and excessive risk of undesirable consequences. Examples include the following: surgical treatment (Chap. 256). 1. Failure by the noncardiologist to recognize important cardiac mani- 4. In patients with CAD (Chap. 267), available practice guidelines festations of systemic illnesses. For example, the presence of mitral should be considered in the decision on the form of treatment (med- stenosis, patent foramen ovale, and/or transient atrial arrhythmia ical, percutaneous coronary intervention, or surgical revasculariza- should be considered in a patient with stroke, or the presence of tion). Mechanical revascularization may be employed too frequently pulmonary hypertension and cor pulmonale should be considered in the United States and too infrequently in Eastern Europe and in a patient with scleroderma or Raynaud’s syndrome. A cardiovas- developing nations. The mere presence of angina pectoris and/or the cular examination should be carried out to identify and estimate the demonstration of critical coronary arterial narrowing at angiography severity of the cardiovascular involvement that accompanies many should not reflexively evoke a decision to treat the patient by revascu- noncardiac disorders. larization. Instead, these interventions should be limited to patients 2. Failure by the cardiologist to recognize underlying systemic disor- with CAD whose angina has not responded adequately to medical ders in patients with heart disease. For example, hyperthyroidism treatment or in whom revascularization has been shown to improve should be considered in an elderly patient with atrial fibrillation and the natural history (e.g., acute coronary syndrome or multivessel unexplained heart failure, and Lyme disease should be considered CAD with left ventricular dysfunction). in a patient with unexplained fluctuating atrioventricular block. A cardiovascular abnormality may provide the clue critical to the rec- ognition of some systemic disorders. For example, an unexplained 232 Basic Biology of the pericardial effusion may provide an early clue to the diagnosis of tuberculosis or a neoplasm. 3. Overreliance on and overutilization of laboratory tests, particularly invasive techniques, for the evaluation of the cardiovascular system. Cardiovascular System Cardiac catheterization and coronary arteriography (Chap. 237) Joseph Loscalzo, Peter Libby, Calum A. MacRae provide precise diagnostic information that may be crucial in devel- oping a therapeutic plan in patients with known or suspected CAD. Although a great deal of attention has been directed to these exami- nations, it is important to recognize that they serve to supplement, not DEVELOPMENTAL BIOLOGY OF THE supplant, a careful examination carried out with clinical and nonin- CARDIOVASCULAR SYSTEM vasive techniques. A coronary arteriogram should not be performed The heart forms early during embryogenesis (Fig. 232-1), circulating in lieu of a careful history in patients with chest pain suspected of blood, nutrients, and oxygen to the other developing organs while having ischemic heart disease. Although coronary arteriography continuing to grow and undergo complex morphogenetic changes. may establish whether the coronary arteries are obstructed and to Early cardiac progenitors arise within crescent-shaped fields of lateral what extent, the results of the procedure by themselves often do not splanchnic mesoderm under the influence of multiple signals and provide a definitive answer to the question of whether a patient’s migrate to the midline to form the linear heart tube: a single layer of complaint of chest discomfort is attributable to coronary atheroscle- endocardium and a single layer of cardiomyocyte precursors. rosis and whether or not revascularization is indicated. The linear heart tube undergoes asymmetric looping, that coordinates with chamber specification and multilayer growth of different regions Despite the value of invasive tests in certain circumstances, they of the heart tube to produce the presumptive atria and ventricles. Cells entail some small risk to the patient, involve discomfort and substantial continue to migrate into the heart at both ends from later, or second, cost, and place a strain on medical facilities. Therefore, they should be heart fields in pharyngeal mesoderm as looping and growth occur. carried out only if the results can be expected to modify the patient’s These cells exhibit distinctive gene expression (e.g., Islet-1) and dis- management. tinctive physiology (e.g., calcium handling), contributing to discrete DISEASE PREVENTION AND MANAGEMENT areas of the adult heart, including the right atrium and the right ven- The prevention of heart disease, especially of CAD, is one of the most tricle. Different embryologic origins of cells within the right and left important tasks of primary health care givers as well as cardiologists. ventricles help explain why some forms of congenital and adult heart Prevention begins with risk assessment, followed by attention to life- diseases affect regions of the heart to varying degrees. style, such as achieving optimal weight, physical activity, and smoking After looping and chamber formation, a series of morphogenetic cessation, and then aggressive treatment of all abnormal risk factors, events divide the left and right sides of the heart, separate the atria such as hypertension, hyperlipidemia, and diabetes mellitus (Chap. 396). from the ventricles, and form the aorta and pulmonary artery from After a complete diagnosis has been established in patients with the truncus arteriosus. Cardiac valves form between the atria and the known heart disease, a number of management options are usually ventricles and between the ventricles and the outflow vessels. Early in available. Several examples may be used to demonstrate some of the development, the single layer of myocardial cells secretes an extracellu- principles of cardiovascular therapeutics: lar matrix rich in hyaluronic acid, or “cardiac jelly,” which accumulates within the endocardial cushions, precursors of the cardiac valves. Sig- 1. In the absence of evidence of heart disease, the patient should be nals from overlying myocardial cells trigger migration, invasion, and clearly informed of this assessment and not be asked to return at phenotypic changes in underlying endocardial cells, which undergo Harrisons_20e_Part6_p1649-p1942.indd 1651 6/1/18 12:48 PM