on 15-Dec-2023 (Fri)

HF is a complex clinical syndrome identified by presence of current or prior characteristic symptoms, such as dyspnea and fatigue, and evidence of cardiac dysfunction as a cause of these symptoms (eg, abnormal left ventricular [LV] and/or right ventricular [RV] filling and elevated filling pressures) [1-5].

From a hemodynamic perspective, HF is a disorder in which the heart cannot pump blood to the body at a rate commensurate with its needs, or can do so only at the cost of high filling pressures [ 6]

There is no single, noninvasive diagnostic test that serves as a gold standard for HF, since it is largely a clinical diagnosis based upon a careful history, physical examination, laboratory and imaging data.

HF caused by LV dysfunction is commonly categorized according to LV ejection fraction (LVEF):

● HF with LVEF ≤40 percent is known as HF with reduced ejection fraction (HFrEF).

● HF with LVEF of 41 to 49 percent is HF with mid-range ejection fraction (HFmrEF).

● HF with LVEF ≥50 percent may be caused by HF with preserved ejection fraction (HFpEF) or a cardiomyopathy (restrictive, hypertrophic, or noncompaction).

Left HF is a common cause of right HF, and most patients with right HF have some element of left HF.

By definition, all patients with HF have current or prior symptoms of HF. Thus, an asymptomatic patient (NYHA class I) can carry a diagnosis of HF only if symptoms of HF were previously present.

While a history alone is insufficient to make the diagnosis of HF, a detailed history remains the single best discriminator to determine the acuity, etiology, and rate of progression of HF, and the history often provides important clues to the cause of HF. (See "Determining the etiology and severity of heart failure or cardiomyopathy".)

Symptoms of HF include those due to excess fluid accumulation (dyspnea, orthopnea, edema, pain from hepatic congestion, and abdominal discomfort due to distention from ascites) and those due to a reduction in cardiac output (fatigue, weakness) that is most pronounced with exertion.

Fluid retention in HF is initiated by the fall in cardiac output, leading to alterations in renal function, due in part to activation of the sodium-retaining renin-angiotensin-aldosterone and sympathetic nervous systems.

In a systematic review that included data from 15 studies of patients with suspected HF, dyspnea was the only symptom or sign with high sensitivity (89 percent), but its specificity was low (51 percent) [7]. Other elements of the history had relatively high specificity but low sensitivity: orthopnea (specificity and sensitivity of 89 and 44 percent) and history of myocardial infarction (89 and 26 percent). However, the sensitivity and specificity of these clinical features are likely to vary among different patient populations.

Acute and subacute presentations (days to weeks) are characterized primarily by shortness of breath, at rest and/or with exertion. Also common are orthopnea, paroxysmal nocturnal dyspnea, and, with right HF, right upper quadrant discomfort due to acute hepatic congestion, which can be confused with acute cholecystitis. Patients with atrial and/or ventricular tachyarrhythmias may complain of palpitations with or without lightheadedness

Chronic presentations (months) differ in that fatigue, anorexia, abdominal distension, and peripheral edema may be more pronounced than dyspnea, as dyspnea may be more subtle and exertional in nature.

Because patients developing HF tend to gradually withdraw from physical activity, they are less likely to perceive symptoms. It is therefore important to identify patient activity levels and symptoms during those activities.

Over time, pulmonary venous capacitance and lymphatic drainage accommodates to the chronic state of volume overload, leading to less or no fluid accumulation in the alveoli, despite the increase in total lung water and high filling pressures.

Patients in this setting present with excessive fatigue and low-output symptoms, and some report dyspnea predominantly with exertion rather than at rest or in the supine position (as with acute HF). Anorexia is secondary to several factors including poor perfusion of the splanchnic circulation, bowel edema, and nausea induced by hepatic congestion

Patients with chronic HF often develop secondary pulmonary hypertension, which can contribute to dyspnea as pulmonary pressures rise with exertion. These patients may also complain of substernal chest pressure, typical of angina. In this setting, elevated RV end-diastolic pressure may cause secondary RV subendocardial ischemia

Some of the physical examination findings of HF, while not very specific on their own, can be very specific in the setting of typical symptoms of HF, but sensitivity is low, so the absence of physical findings does not exclude HF.

In a study of primary care patients, a physical finding of a displaced apical impulse had the best combination of sensitivity, specificity, and positive and negative predictive value of any physical sign of HF with reduced ejection fraction [10]. However, patients with HF and preserved ejection fraction (HFpEF) typically have a nondilated heart, so displacement of the apical impulse is not a helpful finding for diagnosis of HFpEF.

The accuracy of physical signs for the diagnosis of HF was evaluated in the above cited systematic review that included data from 15 studies of patients with suspected HF [7]. Extra heart sounds were highly specific (99 percent) but had low sensitivity (11 percent). In this population, hepatomegaly was also highly specific (97 percent) but had low sensitivity (17 percent). Greater specificity than sensitivity was also seen for cardiomegaly (85 and 27 percent), lung crepitation (81 and 51 percent), edema (72 and 53 percent), and elevated jugular venous pressure (70 and 52 percent).

In contrast, patients with advanced HF may show evidence of decreased tissue perfusion caused by a major decline in cardiac output. Four key findings suggest greater severity of cardiac dysfunction even at steady state: resting sinus tachycardia, narrow pulse pressure, diaphoresis, and peripheral vasoconstriction. The last abnormality is manifested as cool, pale, and sometimes cyanotic extremities (due to the combination of decreased perfusion and increased oxygen extraction). Peripheral vasoconstriction may be absent in patients treated with vasodilators.

A decrease in cardiac output should be suspected when the pulse pressure is reduced below 25 mmHg or if the proportional pulse pressure (pulse pressure divided by systolic pressure) is less than 20 to 25 percent.

Both the cardiac disease itself and the secondary neurohumoral adaptation contribute to the low-output state. Patients compensate for a fall in cardiac output by increasing sympathetic outflow with resultant shunting of the cardiac output to vital organs.

Pulsus alternans, if present, is virtually pathognomonic of severe LV systolic dysfunction. This phenomenon is characterized by evenly spaced alternating strong and weak peripheral pulses. It is best appreciated by applying light pressure on the peripheral arterial pulse and can be confirmed by measuring the blood pressure. When the cuff pressure is slowly released, phase I Korotkoff sounds are initially heard only during the alternate strong beats; with further release of cuff pressure, the softer sounds of the weak beat also appear. Pulsus alternans can also be appreciated based upon variation in the intensity of the first Korotkoff sound during auscultatory blood pressure assessment.

Volume assessment — There are three major manifestations of volume overload in patients with HF: pulmonary congestion, peripheral edema, and elevated jugular venous pressure.

Pulmonary congestion that may manifest as rales is more prominent in acute or subacute disease. As noted above, chronic HF is associated with increases in venous capacitance and lymphatic drainage of the lungs, and alterations in the alveolar capillary interface that reduce permeability and fluid transit; as a result, rales (crackles) are often absent even though the pulmonary capillary pressure is elevated. This also explains why evidence of pulmonary edema is often absent on chest radiographs. Continued sodium retention in this setting preferentially accumulates in the periphery, although a chronic elevation in pulmonary venous pressure can lead to pleural effusions.

The accuracy of clinical evaluation of cardiac filling pressures varies among observers, as illustrated by a study of 116 patients undergoing cardiac catheterization [12]. Signs of elevated right heart filling pressure included increased jugular venous pressure, peripheral edema, and ascites. Signs of elevated left heart filling pressure included findings of elevated right heart filling pressure as well as gallops or rales.

Right and left heart filling pressures were accurately estimated by physical examination in 71 and 60 percent of 215 observations. Examination by staff cardiologists was more accurate than by trainees for right heart pressures (82 versus 67 percent) and left heart pressures (71 versus 55 percent).

The use of echocardiography and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) values did not provide better accuracy than the clinical examination. The accuracy of estimation of right filling pressure by echocardiographic examination of the inferior vena cava (75 percent) was similar to the accuracy of physical examination. The accuracy of estimates of left heart filling pressures by NT-proBNP (67 percent) and by echocardiography E/e’ ratio (60 percent) were also similar to physical examination.

Ventricular chamber size can be estimated by precordial palpation. An apical impulse that is laterally displaced past the midclavicular line is usually indicative of LV enlargement. LV dysfunction can also lead to sustained apical impulse, which may be accompanied by a parasternal lift in the setting of RV hypertrophy or enlargement. The S3 may be palpable in severe ventricular failure.

In addition, in a phonocardiographic study of patients who were undergoing cardiac catheterization, an S3 was not very sensitive (40 to 50 percent) for the detection of an elevated LV end-diastolic pressure or a reduced LV ejection fraction (LVEF); however, an S3 was highly specific (90 percent) for these parameters and for an elevated serum BNP concentration [15]. Similarly, an S3 has a low sensitivity (eg, 4 to 11 percent) but high specificity (eg, 99 percent) for clinical diagnosis of HF [7,8].

An S3 (third heart sound) is associated with left atrial pressures exceeding 20 mmHg and increased LV end-diastolic pressures (>15 mmHg). However, there is appreciable interobserver variability in the ability to detect an S3 that cannot be solely explained by the experience of the observer [13,14]

Physical signs of pulmonary hypertension can include increased intensity of P2, a murmur of pulmonary or tricuspid insufficiency, a parasternal lift, and a palpable pulmonic tap (felt in the left second intercostal space). Elevation in central venous pressure accompanying pulmonary hypertension and RV failure often leads to pulsatile hepatomegaly and ascites.

(See "Auscultation of heart sounds" and "Auscultation of cardiac murmurs in adults" and "Examination of the precordial pulsation" and "Congestive hepatopathy".)

Most patients with HF with reduced ejection fraction (HFrEF) have a significant abnormality on an electrocardiogram (ECG). A normal ECG makes LV systolic dysfunction unlikely (98 percent negative predictive value) [16].

In contrast, patients with HF with preserved ejection fraction (HFpEF) commonly display a normal 12-lead ECG, though the presence of atrial fibrillation (AF) or paced rhythm greatly increase the probability that HFpEF is present [9].

NP levels are often (but not exclusively) elevated in patients with HFrEF, but may be normal in a substantial number of patients with HFpEF. Thus, the presence of an elevated NP level increases the likelihood that HF is present, but a normal level does not exclude it, particularly in patients with a normal LVEF or obesity. Conversely, elevations can be caused by elevated right heart pressures, renal dysfunction, or many systemic diseases.

Liver function tests, which may be affected by hepatic congestion. In one study, gamma-glutamyltransferase level >2 times the upper limit of normal was the only standard initial blood test that added diagnostic value to the history and physical examination [8]. However, NT-proBNP was the most powerful supplementary test. (See "Congestive hepatopathy".)

Findings suggestive of HF include cardiomegaly (cardiac to thoracic width ratio above 50 percent), cephalization of the pulmonary vessels, Kerley B-lines, and pleural effusions (image 1A-E). The cardiac size and silhouette may also reveal signs of congenital anomalies (ventricular or atrial septal defect) or valvular disease (mitral stenosis or aortic stenosis). As noted above, due to chronic adaptive changes in the lungs, patients with very high filling pressures and chronic HF will often display clear lung fields on plain chest film.

The limitations of a chest radiograph are even more dramatic in patients with HFpEF, where the sensitivity of cardiomegaly is 24 percent and pleural effusion is only 9 percent. In contrast, the same study found that specificity for these findings is excellent (96 and 98 percent, respectively) [9].

Low-specificity/high-sensitivity findings:

- Symptoms: Dyspnea on exertion, fatigue, weight gain

- Signs: Peripheral edema

- Clinical feature: Age >60 years

Intermediate-specificity/intermediate-sensitivity findings:

- Signs: Rales (crackles)

- Chest radiograph: Findings consistent with cardiomegaly or pleural effusion

- ECG: Atrial fibrillation (AF), left atrial enlargement, LV hypertrophy, or pathologic Q waves

- Serum natriuretic peptide:

Age <50: N-terminal pro-B-type natriuretic peptide (NT-proBNP) 125 to 450 pg/mL or BNP 35 to 100 pg/mL

Age 50 to 75: NT-proBNP 450 to 900 pg/mL or BNP 35 to 100 pg/mL

Age >75: NT-proBNP 900 to 1800 pg/mL or BNP 35 to 100 pg/mL

- Clinical feature: Coronary artery disease (including prior myocardial infarction), or moderate valvular regurgitation or stenosis

- Echocardiogram: Left atrial volume index >34 mL/m², E/A ≥0.9 and <2.1, or E/A ≤0.8 and E >50 cm/s

E is peak velocity of early LV filling, A is peak velocity of late LV filling, and e' is peak early diastolic velocity of LV myocardium adjacent to the mitral annulus.

High-specificity/low-sensitivity findings

- Symptoms: Orthopnea, paroxysmal nocturnal dyspnea

- Signs: Elevated jugular venous pressure, a third heart sound (S3), pulsus alternans, or laterally displaced point of maximal impulse (PMI)

- Chest radiograph: Findings consistent with pulmonary edema (cephalization of pulmonary vessels and Kerley B lines, with or without peribronchial cuffing)

- Serum natriuretic peptide:

Age <50: NT-proBNP >450 pg/mL or BNP >100 pg/mL

Age 50 to 75: NT-proBNP >900 pg/mL or BNP >100 pg/mL

Age >75: NT-proBNP >1800 pg/mL or BNP >100 pg/mL

- Clinical feature: Severe valvular regurgitation or stenosis

- Echocardiogram: LVEF <30 percent, LV end-diastolic dimension >5.8 cm (men) or >5.2 (women); E/e’ ≥15, E/A ≥2.1, or inferior vena cava >2.1 cm with collapse during sniff <50 percent

Many patients with LVEF <50 percent without HF require guideline-directed therapy to reduce cardiovascular risk (particularly those with LVEF ≤40 percent, prior myocardial infarction, and/or hypertension). However, a diagnosis of HF has important therapeutic implications since some pharmacologic agents are indicated for HF and not for asymptomatic LV systolic dysfunction.

Some studies have used depressed LVEF as a means of identifying patients with HF, but this approach is inaccurate since approximately half of patients with HF have a preserved LVEF, and some patients with depressed LVEF do not have the clinical syndrome of HF.

While no single echocardiographic parameter is diagnostic of HF, most patients with HF have one or more echocardiographic abnormality (eg, reduced LVEF, diastolic dysfunction, LV hypertrophy, valve stenosis, valve regurgitation, left atrial enlargement, or elevated estimated pulmonary artery systolic pressure).

Natriuretic peptide levels should be interpreted in the context of other clinical information; they may lend weight to the diagnosis of HF or trigger consideration of HF but should NOT be used in isolation to diagnose or exclude HF [17].

In the above cited systematic review that included 15 studies, BNP or NT-proBNP levels had relatively high sensitivity (both 93 percent) and more limited specificity for diagnosis of HF (74 and 65 percent) [7].

s noted below, studies developing and validating diagnostic rules for HF have found that the BNP or NT-proBNP levels add greater diagnostic value to the history and physical examination than other initial tests (ECG, chest radiograph, and initial blood tests) [ 7,8].

NT-proBNP — In normal subjects, the plasma concentrations of BNP and NT-proBNP are similar (approximately 10 pmol/L). However, in patients with LV dysfunction, plasma NT-proBNP concentrations are approximately fourfold higher than BNP concentrations [30].

The optimal values for distinguishing HF from other causes of dyspnea vary with patient age. In a large multicenter study, for patients <50, 50 to 75, and >75 years of age, the optimal plasma NT-proBNP cutoffs for diagnosing HF were 450 pg/mL, 900 pg/mL, and 1800 pg/mL, respectively [31]. Overall, these cutoffs yielded a sensitivity and specificity of 90 and 84 percent, respectively. Across the entire population, NT-proBNP levels below 300 pg/mL were optimal for excluding a diagnosis of HF, with a negative predictive value of 98 percent.

As noted above, BNP and NT-proBNP levels are frequently normal in patients with HFpEF [33-35].

In patients receiving sacubitril-valsartan, which contains an angiotensin receptor blocker (valsartan) and a neprilysin inhibitor (sacubitril), plasma BNP levels will be elevated due to the inhibition of BNP degradation by the neprilysin inhibitor. NT-proBNP retains its utility as an HF marker since its levels are not affected by the neprilysin inhibitor.

● Patients may present with more than one cause of dyspnea (such as pneumonia and an exacerbation of HF). Thus, a high plasma BNP or NT-proBNP concentration does not exclude the presence of other diseases.

● In some patients with acute decompensated HF, plasma BNP or NT-proBNP levels are not diagnostic.

● Right HF and pulmonary hypertension are associated with elevations in plasma BNP and NT-proBNP. However, when right HF is due solely to lung disease and not due to secondary pulmonary hypertension from left-sided heart disease or as part of a global cardiomyopathy, elevated plasma BNP may be misinterpreted since dyspnea in these patients is due to lung disease not left HF.

● Plasma BNP and NT-proBNP levels tend to be lower in obese patients and are elevated in patients with renal failure and some acute noncardiac illnesses such as sepsis. Greater increases in NT-proBNP than BNP levels are observed in renal failure.

Zunächst wird ein Überblick über wesentliche Begriffe und gängige Techniken der Computer- architektur gegeben. Außerdem wird ein Einblick in den Grobaufbau von Computern vermit- telt (Kapitel 1 bis 4). Welche Arten von Computern gibt es? Welches sind die Gemeinsamkei- ten und Unterschiede? Wie kann man Computer schneller machen? Das sind einige der Fragen, die beantwortet werden.

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