Cardiomegaly is most similar to cardiac hypertrophy

Cardiomegaly on Chest X-Ray

TABLE 11. Diagnosis of Cardiac Tamponade

ECG, electrocardiogram;IVC, inferior vena cava;LA, left atrium;LV, left ventricle;QRS, Q wave, R wave, S wave;RA, right atrium;RV, right ventricle.

From Vincent JL et al:Textbook of critical care, ed 7, Philadelphia, 2017, Elsevier.

Evaluation of Athletes

Cardiomegaly is often seen in athletes due to endurance training such as long-distance running, which causes a sustained volume load to the heart, resulting in four-chamber enlargement and increased stroke volume at rest and exercise. Strength training such as weight lifting causes a pressure load to the heart accompanied by normal left ventricular wall thickness. Some sports, such as basketball, present a combination of the two types of loads. ECGs may show frequent signs of left ventricular hypertrophy in around 40% of athletes, T-wave inversion in precordial leads V1 to V4 in 14% of African-American athletes, longer QT intervals than in the general population, frequent PVCs, and sinus bradycardia as well as various degrees of AV block due to a high vagal tone. These ECG changes can mimic ARVD/C, Brugada syndrome, or long QT syndrome and may make diagnostic decisions difficult in this population. More importantly, the risk assessment for SCD during athletic activity and permitting them to return to play can be difficult.17

Cardiac Myocyte Hypertrophy

Two basic patterns of cardiac hypertrophy occur in response to hemodynamic overload (Fig. 23.7). In pressure overload hypertrophy (e.g., with aortic stenosis or hypertension), increased systolic wall stress leads to the addition of sarcomeres in parallel, an increase in myocyte cross-sectional area, and increased LV wall thickening. This pattern of remodeling has been referred to as “concentric” hypertrophy (Fig. 23.7A) and has been linked with alterations in Ca2+/calmodulin-dependent protein kinase II–dependent signaling22 (Fig. 23.8). By contrast, in volume overload hypertrophy (e.g., with aortic and mitral regurgitation), increased diastolic wall stress leads to an increase in myocyte length with the addition of sarcomeres in series, thereby engendering increased LV ventricular dilation. This pattern of remodeling has been referred to as “eccentric” hypertrophy (because of the position of the heart in the chest), or a “dilated” phenotype (seeFig. 23.7A), and has been linked with protein kinase B (Akt) activation22 (seeFig. 23.8). Patients with HF classically present with a dilated left ventricle with or without LV wall thinning. The myocytes from these failing ventricles have an elongated appearance that is characteristic of myocytes obtained from hearts subjected to chronic volume overload.

Cardiac myocyte hypertrophy also leads to changes in the biologic phenotype of the myocyte that are secondary to reactivation of portfolios of genes normally not expressed postnatally. The reactivation of these fetal genes, the so-called fetal gene program, also is accompanied by decreased expression of a number of genes that are normally expressed in the adult heart. As discussed later, activation of the fetal gene program may contribute to the contractile dysfunction that develops in the failing myocyte. As shown inFig. 23.8, the stimuli for the genetic reprogramming of the myocyte include mechanical stretch/strain of the myocyte, neurohormones (e.g., NE, angiotensin II), inflammatory cytokines (e.g., TNF, IL-6), other peptides and growth factors (e.g., ET), and ROS (e.g., superoxide, NO). These stimuli occur both locally within the myocardium, where they exert autocrine/paracrine effects, and systemically, where they exert endocrine effects.

The early stage of cardiac myocyte hypertrophy is characterized morphologically by increases in the number of myofibrils and mitochondria, as well as enlargement of mitochondria and nuclei. At this stage, the cardiac myocytes are larger than normal, but with preservation of cellular organization. As hypertrophy continues, there is an increase in the number of mitochondria, as well as the addition of new contractile elements in localized areas of the cell. Cells subjected to longstanding hypertrophy show more obvious disruptions in cellular organization, such as extremely enlarged nuclei with highly lobulated membranes, accompanied by the displacement of adjacent myofibrils with loss of the normal registration of the Z-bands. The late stage of hypertrophy is characterized by loss of contractile elements (myocytolysis) with marked disruption of Z-bands and severe disruption of the normal parallel arrangement of the sarcomeres, accompanied by dilation and increased tortuosity of T tubules.

Diagnostic Testing

Development of Cardiac Hypertrophy

LV remodeling describes the changes in ventricular mass, volume, shape, and composition in response to mechanical stress and systemic neurohormonal activation. Development of cardiac hypertrophy is the primary chronic adaptation of the heart to compensate for pump failure. This hypertrophy occurs mainly by increasing the number of myofibrils per cell, because the heart has very limited ability to produce new cells (hyperplasia). New myofibrils arrange in series in response to an increase in chamber volume (leading to dilation over time) and in parallel when responding to higher pressure loads (leading to increased chamber wall thickness). LV hypertrophy leads to a less efficient round LV chamber compared to the normal elliptical shape.33 In addition to myofibril hypertrophy, mitochondrial mass expands, leading to additional ATP provision for the expanded myofibril mass. However, impaired mitochondrial function is recognized in heart failure, with reduced energy production and higher oxidative stress.34

Initially, hypertrophy leads to improved function of each myocardial cell but at a higher energy cost. Hypertrophy is associated with myosin and other sarcomere protein isoform shifts, with related slowing of contraction, prolongation of time to peak tension, and reduced rate of relaxation.35 With the continued influence of volume overload, myofibril mass expands more than mitochondrial mass. Relative capillary blood flow is also reduced, leading to progressive myocyte death with fibrosis and increased stress on the remaining myocytes. This leads to extracellular matrix expansion, which is one of the negative effects of pathological LV remodeling. Thus the remodeling response, if allowed to continue, eventually becomes maladaptive, accelerating myocyte death, reducing microvascular perfusion, increasing extracellular collagen, and reducing pump function.36,37 This process gradually occurs as a normal part of aging.38

CARDIOMEGALY ON CHEST X-RAY

FIGURE 3-18. Approach to the patient with cardiomegaly. When cardiomegaly is found on the chest radiograph, the history and physical examination should be reviewed and an electrocardiogram (ECG) performed before obtaining a two-dimensional Doppler echocardiographic study. Cardiomegaly may be explained by left ventricular dilation, biventricular dilation, right ventricular dilation, or pericardial abnormalities, or it may be found to be spurious on the echocardiogram. Rarely, isolated abnormalities of the atrium, particularly the left atrium, may cause abnormalities on the chest radiograph but will not cause true cardiomegaly. Depending on the echocardiographic findings, further tests can help elucidate the cause of echocardiographically confirmed cardiomegaly. CT, Computer tomography; MRI, magnetic resonance imaging; R/O, rule out.

Imaging Technique and Findings

Chest Radiography

In infants, cardiomegaly and increased pulmonary vascular markings can be seen on the radiograph. In older children, the heart size is often normal, but if cardiomegaly is present, it is usually caused by left ventricular enlargement. There are two pathognomonic signs on the plain chest radiograph in older children. The first is the figure 3 sign, which appears to the left of the mediastinum and is caused by pre- and post-stenotic dilation of the aorta (Fig. 46-18). The second sign is rib notching, which is usually not seen until 4 years of age, although appearance in the first year has been described.42 By adulthood, around three-quarters of untreated patients have rib notching. It is best seen posteriorly in the medial third of the lower borders of the fourth to eighth ribs, where the intercostal artery crosses the rib (see Fig. 46-18). The notching in coarctation is classically bilateral, to be differentiated from the unilateral notching seen after a classical Blalock–Taussig shunt, although unilateral notching can also occur with coarctation when a subclavian artery arises aberrantly distal to the site of obstruction.

In those with interruption the heart is usually left sided with normal abdominal and bronchial arrangement. Cardiomegaly, particularly enlargement of the left atrium, is present in nine-tenths of neonates.43 Increased pulmonary vascular markings with pulmonary oedema are also the norm. In the rare patients who survive infancy untreated, more specific signs can be seen,44 including absence of the aortic knob, a midline trachea, absence of an aortic impression on the barium swallow, and termination of the descending aorta at the level of the pulmonary trunk. Rib notching can also be seen on the side of the subclavian arteries arising from the ascending aorta in the presence of a restrictive or closed arterial duct. A narrow mediastinum may suggest absence of the thymus gland, a feature of Di George syndrome.

Chest X-Ray

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Among children: Cardiomegaly and plethora may be present when PVR falls. This is likely to be absent and the chest x-ray (CXR) may appear normal when PVR remains elevated.

Among adults: In the circumstance of an uncorrected complete AVSD and pulmonary vascular disease, mild cardiomegaly will often be present (more severe if cardiac dysfunction ensues) with large proximal pulmonary arteries (sometimes with calcification) and small peripheral pulmonary arteries (peripheral pruning).

Among children and adults with significant common AV valve regurgitation: pulmonary venous markings will increase with upper lobe blood diversion.

Acute rheumatic carditis

Heart murmurs, cardiomegaly, and congestive heart failure are all signs and symptoms of acute rheumatic carditis, although a subset of patients are asymptomatic. Pleuritic chest discomfort or pain and pericardial friction rub are indicators of pericarditis, which is present in approximately 10% of patients. The pericardial effusion may be large, but cardiac tamponade is rare. Valvular inflammation and deformity cause new or changing organic murmurs, most commonly mitral regurgitation. Aortic regurgitation and systolic ejection murmurs are occasionally observed. The classical Carey Coombs mid-diastolic murmur is rare and is caused by a rapid overflow of the mitral valve.

Mitral regurgitation is the most common early valvular finding and may be accompanied by aortic regurgitation. Isolated aortic regurgitation is less frequent. Mitral regurgitation can be caused by a prolapsed mitral valve, which chiefly involves the anterior leaflet, with minimal leaflet redundancy. This presentation is in contrast with that in myxomatous disease, which more commonly involves the posterior leaflet and is associated with prominent leaflet redundancy. Valve prolapse is due to annular dilation and chordal elongation. Aortic or mitral stenosis is atypical at presentation. Congestive heart failure is the most life-threatening feature of ARF and can develop if severe valvular damage occurs in addition to cardiac dysfunction. Congestive heart failure occurs in 5% to 10% of initial ARF episodes and is more frequent during recurrences. This complication must be treated rapidly and aggressively with diuretics and antiinflammatory drugs. Myocarditis in the absence of valvulitis is unlikely to be rheumatic. Varying degrees of heart blockage can be observed on electrocardiography. Second- and third-degree blockage may require short-term use of a pacemaker if it is associated with congestive heart disease.

The incidence of carditis during the initial ARF attack varies from 40% to 91%, depending on the selection of patients and whether the diagnosis is made on a clinical basis or in combination with echocardiography (see Table 111.1).