on 30-Nov-2021 (Tue)

Ischemia, which is caused by an imbalance between the 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 accumulation, with peripheral edema (Chap. 37) or pulmonary conges- tion and dyspnea

Obstruction to blood flow, as occurs in valvular stenosis, can cause symptoms resembling those of myocardial failure (Chap. 252). Cardiac arrhythmias often develop suddenly, and the resulting symptoms and signs—palpitations (Chap. 39), dyspnea, hypotension, and syncope (Chap. 18)—generally occur abruptly and may disappear as rapidly as they develop.

Although dyspnea, chest discomfort, edema, and syncope are car- dinal manifestations of cardiac disease, they occur in other conditions as well. Thus, dyspnea is observed in disorders as diverse as pulmo- nary disease, marked obesity, and anxiety (Chap. 33). Similarly, chest discomfort may result from a variety of noncardiac and cardiac causes other than myocardial ischemia (Chap. 11). Edema, an important find- ing in untreated or inadequately treated heart failure, also may occur with primary renal disease and in hepatic cirrhosis (Chap. 37). Syncope occurs not only with serious cardiac arrhythmias but in a number of neurologic conditions as well (Chap. 18). Whether heart disease is responsible for these symptoms frequently can be determined by carrying out a careful clinical examination (Chap. 234), supplemented by noninvasive testing using electrocardiography at rest and during exercise (Chap. 235), echocardiography, roentgenography, and other forms of myocardial imaging

Many patients with cardiovascular disease may be asymptomatic both at rest and during exertion but may present with an abnormal physical finding such as a heart murmur, elevated arterial pressure, or an abnormality of the electrocardiogram (ECG) or imaging test

The majority of heart murmurs are midsystolic and soft (grades I–II/VI). When such a murmur occurs in an asymptomatic child or young adult without other evidence of heart disease on clinical examination, it is usually benign and echocardiography generally is not required. By contrast, two-dimensional and Doppler echocardiography (Chap. 236) are indicated in patients with loud systolic murmurs (grades ≥III/VI), especially those that are holosystolic or late systolic, and in most patients with diastolic or continuous murmurs.

Pulsus paradoxus refers to a fall in systolic pressure >10 mmHg with inspiration that is seen in patients with pericardial tamponade but also is described in those with massive pulmonary embolism, hemorrhagic shock, severe obstructive lung disease, and tension pneumothorax. Pulsus paradoxus is measured by noting the difference between the systolic pressure at which the Korotkoff sounds are first heard (during expiration) and the systolic pressure at which the Korotkoff sounds are heard with each heartbeat, independent of the respiratory phase. Between these two pressures, the Korotkoff sounds are heard only intermittently and during expiration. The cuff pressure must be decreased slowly to appreciate the finding. It can be difficult to mea- sure pulsus paradoxus in patients with tachycardia, atrial fibrillation, or tachypnea. A pulsus paradoxus may be palpable at the brachial artery or femoral artery level when the pressure difference exceeds 15 mmHg. This inspiratory fall in systolic pressure is an exaggerated consequence of interventricular dependence.

Pulsus alternans, in contrast, is defined by beat-to-beat variability of pulse amplitude. It is present only when every other phase I Korotkoff sound is audible as the cuff pressure is lowered slowly, typically in a patient with a regular heart rhythm and independent of the respira- tory cycle. Pulsus alternans is seen in patients with severe LV systolic dysfunction and is thought to be due to cyclic changes in intracellular calcium and action potential duration. When pulsus alternans is associated with electrocardiographic T-wave alternans, the risk for an arrhythmic event appears to be increased.

ny condition that leads to an alteration in LV structure or function can predispose a patient to developing HF. Although the etiology of HF in patients with a preserved EF differs from that of patients with depressed EF, there is considerable over- lap between the etiologies of these two conditions.

In 20–30% of the cases of HF with a depressed EF, the exact etiologic basis is not known. These patients are referred to as having nonische- mic, dilated, or idiopathic cardiomyopathy if the cause is unknown (Chap. 254). Prior viral infection or toxin exposure (e.g., alcoholic or chemotherapeutic) also may lead to a dilated cardiomyopathy. More- over, it is becoming increasingly clear that a large number of cases of dilated cardiomyopathy are secondary to specific genetic defects, most notably those in the cytoskeleton. Most forms of familial dilated cardiomyopathy are inherited in an autosomal dominant fashion

Dilated cardiomyopathy also is associated with Duchenne’s, Becker’s, and limb-girdle muscular dystrophies. Con- ditions that lead to a high cardiac output (e.g., arteriovenous fistula, anemia) are seldom responsible for the development of HF in a normal heart; however, in the presence of underlying structural heart disease, these conditions can lead to overt HF.

HF is a progressive disorder that is initiated after an index event either damages the heart muscle, with a resultant loss of functioning cardiac myocytes, or, alternatively, disrupts the ability of the myocardium to generate force, thereby pre- venting the heart from contracting normally. This index event may have an abrupt onset, as in the case of an MI; it may have a gradual or insidious onset, as in the case of hemodynamic pressure or volume overloading; or it may be hereditary, as in the case of many of the genetic cardiomyopathies. Regardless of the nature of the inciting event, the feature that is common to each of these index events is that they all in some manner produce a decline in the pumping capacity of the heart.

Although the precise reasons why patients with LV dysfunction may remain asymptomatic is not certain, one potential explanation is that a number of compensatory mechanisms become activated in the presence of cardiac injury and/or LV dysfunction allowing patients to sustain and modulate LV function for a period of months to years. The compensatory mechanisms that have been described thus far include (1) activation of the renin-angiotensin-aldosterone system (RAAS) and the adrenergic nervous system, which are responsible, respectively, for maintaining cardiac output through increased retention of salt and water (Fig. 252-2) and (2) increased myocardial contractility. In addi- tion, a family of countervailing vasodilatory molecules are activated, including the atrial and brain natriuretic peptides (ANP and BNP), bradykinin, prostaglandins (PGE 2 and PGI 2 ), and nitric oxide (NO), that offset the excessive peripheral vascular vasoconstriction. Many of these vasodilatory peptides, including bradykinin and natriuretic peptides, are degraded by a neprilysin, which is a membrane-bound peptidase. These compensatory mechanisms are able to modulate LV function within a physiologic/homeostatic range so that the functional capacity of the patient is preserved or is minimally depressed. Thus, patients may remain asymptomatic or minimally symptomatic for a period of years; however, at some point patients become overtly symp- tomatic, with a resultant striking increase in morbidity and mortality rates.

In contrast to our understanding of the pathogenesis of HF with a depressed EF, our understanding of the mechanisms that contribute to the development of HF with a preserved EF is still evolving. That is, although diastolic dysfunction (see below) was thought to be the only mechanism responsible for the development of HF with a preserved EF, community-based studies suggest that additional extracardiac mechanisms may be important, such as increased vascular stiffness and impaired renal function.