Cardiovascular Involvement by Systemic Diseases

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Chapter 82

Cardiovascular Involvement by Systemic Diseases

Numerous systemic diseases can affect the heart and great vessels and are important causes of cardiac dysfunction. These systemic diseases include both prenatal and postnatal toxic and infectious exposures, adverse effects of therapeutic agents, and various nutritional, metabolic, inflammatory, granulomatous, infectious, and autoimmune entities. Endocrine, circulatory, and blood disorders frequently have secondary cardiac effects. Primary cardiac tumors can occur in association with underlying systemic disorders; although rare, neoplasms elsewhere can metastasize to the heart or locally invade the great vessels or pericardium. Both congenital and secondary lung and chest wall abnormalities are associated with structural and functional cardiac abnormalities.

These entities and the spectrum of their cardiac effects are outlined in Table 82-1. We have included both common diseases that have cardiovascular features and uncommon lesions in which cardiovascular manifestations are prominent. A small number of selected entities are discussed in the following sections. Many of the lesions outlined in Table 82-1 overlap with other chapters and thus are not specifically discussed here. Some well-known syndromes, such as Marfan syndrome, have both cardiac and other organ manifestations, but because they are covered in other chapters, further discussion is omitted here (see Chapter 79).

Toxins/Drugs

Fetal Alcohol Exposure

Fetal alcohol syndrome is a common disorder affecting 0.5 to 2.0 per 1000 live births. Affected infants have moderate to severe growth retardation both in the prenatal and postnatal period, along with a characteristic facies. Most children with fetal alcohol syndrome have associated neurologic problems including mental retardation and learning disabilities, as well as altered behavior.1,2

Cardiac malformations are common with fetal alcohol exposure; the most frequent is ventricular septal defect. Other cardiac anomalies include pulmonary artery hypoplasia, coarctation or interruption of the aortic arch, atrial septal defect, patent ductus arteriosus, and tetralogy of Fallot (Fig. 82-1).3

Infectious, Inflammatory, and Autoimmune Disorders

Infectious Aortitis

Overview: Acute infectious aortitis in children often is caused by bacterial septicemia originating from infected lines and intravascular devices and from valvular endocarditis or occasionally by direct spread from an adjacent infection or abscess (Fig. 82-2).4 Staphylococci and streptococci are the organisms most frequently responsible for acute infectious aortitis.4,5 Predisposing conditions include congenital heart disease and an immunocompromised state. Once they are in the bloodstream, virulent organisms may adhere to and invade the aortic wall. The resulting inflammation leads to suppurative necrosis that weakens the aortic wall and forms an aneurysm (see Fig. 82-2, A). A contained leak may lead to pseudoaneurysm formation (see Fig. 82-2, B). Staphylococcal aortitis is particularly prone to overt rupture of the aneurysm or pseudoaneurysm and is the most serious complication of infectious aortitis. Fungal agents, especially Aspergillus or Candida, also may be the causative agent of infectious aortitis, especially in immune-compromised individuals.6 Syphilitic and tuberculous aortic aneurysms are rare complications of chronic infection by those organisms and are very uncommon in children.

Diagnosis of infectious aortitis is difficult because many children with infected aneurysms are asymptomatic or they present with nonspecific complaints, such as fever and abdominal or back pain. Commonly used laboratory markers of infection can be normal. One adult study showed that blood cultures were negative in 28% of cases and white blood cell counts were normal in 42% of cases; however, an elevated erythrocyte sedimentation rate, a nonspecific finding of inflammation, was found in 92% of patients.5

Imaging: Few clinical studies have evaluated the imaging appearance and distribution of infected aortic aneurysms in children. Experience from adult patients suggests that these aneurysms are more often saccular (93%) than fusiform (7%) and can be distributed throughout the course of the aorta: 6% in the ascending aorta, 23% in the descending thoracic, 19% in the thoracoabdominal aorta, 10% in the juxtarenal aorta, and 32% in the infrarenal aorta.7 Periaortic fluid, stranding, or a soft tissue mass was present in 48% of patients with infectious aortitis. Periaortic gas, a specific sign, was present in only 7%. Rapid progression of aneurysm size was found in infected aneurysms in both adults and children.7 Computed tomographic angiography (CTA) and magnetic resonance angiography (MRA) imaging have largely supplanted conventional angiography in the diagnosis of aortic aneurysms and their complications (see Fig. 82-2). Ultrasound may be an initial screening examination but usually is not definitive enough to support management decisions.

Treatment: Antibiotic treatment with the goal of eradicating the offending organism is the first step in the treatment of infectious aortitis.5 At the same time, imaging to document stability of the aortic lumen is necessary. If an aneurysm has formed, it should be surgically repaired after an adequate period of antibiotic treatment.4,5 Deployment of endovascular stent grafts in infected aortic aneurysms has been attempted.8 Although this deployment is not considered a treatment of choice, it may be useful to act as a bridge to open surgical repair, especially in the presence of low-virulence organisms or rapidly expanding aneurysms.

Takayasu Arteritis

Overview: Takayasu arteritis, also known as pulseless arteritis, is a chronic inflammatory arteritis of large vessels.9 The aorta is the artery that is most commonly involved, with the abdominal aorta involved in 59% to 75% of cases and the thoracic aorta involved in 40% to 56% of cases. Takayasu arteritis involvement is more common in the systemic arteries than in the pulmonary arteries.10 Takayasu arteritis is a rare disease, occurring in 2.6 per 1 million people in North America.11 It is more common in patients of Asian descent, and females make up 80% to 90% of patients.

Diagnosis of Takayasu arteritis is based on patient symptoms, physical findings, clinical laboratory values, serologic markers, and vascular findings.9 The American College of Rheumatology criteria include arm or leg claudication, age younger than 40 years, a blood pressure difference between extremities of greater than 10 mm Hg, subclavian or aortic bruit, decreased brachial artery pulse, and aortic or branch narrowing.12 Three of these criteria provide a diagnosis of Takayasu arteritis with a sensitivity of 90.5% and a specificity of 97.8%.11 Other clinical manifestations of Takayasu arteritis that are not involved in diagnosis include fever, headache, neurologic symptoms including stroke, postural dizziness, arthralgias, weight loss, myalgias, and systemic or pulmonary hypertension.11,13

Takayasu arteritis has a triphasic pattern: a systemic nonvascular phase, a vascular inflammatory phase, and a quiescent “burnt out” phase, although the inflammatory and fibrotic changes often overlap.10,11 In children, a long delay often occurs before Takayasu arteritis is diagnosed, especially when systemic symptoms predominate.11,13,14

The lesions of Takayasu arteritis are segmental with a patchy distribution. The vasculitis can lead to stenosis, occlusion, and aneurysm formation.10 Severe stenosis or occlusive thrombosis of the pulmonary vasculature may lead to pulmonary infarction and pulmonary hypertension.15 Cardiac symptoms include aortic regurgitation, dilated cardiomyopathy, myocarditis, pericarditis, congestive heart failure, and myocardial ischemia.

Etiology and Classification: The specific cause of Takayasu arteritis is unknown, but it is probably a T-cell–mediated autoimmune process. Infection, particularly tuberculosis, has been linked to the development of Takayasu arteritis, especially in children.13 The diseased vessel wall is thickened and shows granulomatous changes from the adventitia to the media. Giant cell (or temporal arteritis) has an identical pathologic appearance to Takayasu arteritis but affects an older population and typically involves the temporal artery.16

Takayasu arteritis currently is divided into six types depending on the location of aortic involvement. Coronary (C+) or pulmonary (P+) involvement may occur in all types (Fig. 82-3).10

Imaging: Vascular stenosis and aneurysm are the primary causes of mortality and morbidity and therefore should be evaluated with angiographic techniques. Conventional angiography has been the gold standard for diagnosis, but it is being supplanted by MRA (e-Fig. 82-4 and Fig. 82-5).10,11 MRA has several advantages, including its lack of ionizing radiation, its noninvasive nature, and its ability to show abnormal vascular wall signal and thickening before luminal narrowing becomes apparent.9 It also does not require iodinated contrast agents. Active inflammation is suggested when a high T2 signal is noted within the vessel wall (see Fig. 82-5). Vessel wall enhancement can be seen with the administration of gadolinium and also is used to gauge the activity of the inflammatory process (see e-Fig. 82-4).10,11,14 Inversion recovery delayed enhancement of the vessel wall also may be seen; the significance of this phenomenon is uncertain.11

Other imaging studies can be used to show the abnormalities of Takayasu arteritis. Ultrasound can show vessel wall thickening and CTA may demonstrate mural thickening and wall enhancement, as well as luminal dilation, narrowing, or occlusion (see Fig. 82-5).9 Fluorodeoxyglucose positron emission tomography uptake also may be useful in evaluating active inflammation.9,11

Treatment and Follow-up: Medical therapy of Takayasu arteritis initially focuses on the suppression of the immunologic responses with corticosteroids, methotrexate, azathioprine, and cyclophosphamide. In refractory Takayasu arteritis, the anti–tumor necrosis factor-α agents Etanercept and Infliximab have been used to achieve sustained remission.17 Follow-up with MRA or CTA helps document stability or progression of the vascular abnormalities and their complications.9,14

Patients with renovascular hypertension, severe coarctation of the aorta, claudication, progressive aneurysm enlargement, coronary artery disease, or cervicocranial vessel stenosis may benefit from surgical revascularization.13 Bypass grafts, either synthetic or autologous, can be used, but restenosis has occurred in up to one third of cases in which synthetic grafts were used and in approximately 10% of procedures in which an autologous vessel was used. Other postoperative complications include heart failure, intractable hypertension, and graft deterioration with pseudoaneurysm formation. Postsurgical aneurysm formation at the anastomosis is a complication seen in up to 34% of patients. Angioplasty has been used with success in patients with Takayasu arteritis who have vascular stenosis, with an initial success rate of 92% and a restenosis rate of 22%. Surgical options preferably are performed during disease remission.13

Other Vasculitides

Aneurysmal disease of the aorta, which generally afflicts older patients, is a rare complication of systemic lupus erythematosus. The exact pathophysiology of the aortic aneurysm is unknown. It may be caused directly by the systemic lupus erythematosus–related inflammation of the vessel wall or as a result of chronic steroid treatment and the resultant accelerated aortic atherosclerosis.18 Sarcoidosis has been reported as a rare cause of large-vessel vascular stenosis, and it has been recommended that children with early-onset sarcoidosis be evaluated for occlusive arterial disease.19

Other rare causes of vasculitis, especially in the pulmonary artery, include Behçet syndrome and Wegener granulomatosis.12,20 Behçet syndrome is a multisystem inflammatory disease of unknown cause. Classically, Behçet syndrome describes a combination of recurrent aphthous ulcers, genital ulceration, and uveitis. It also involves the central nervous system in 10% to 30% of cases and the vascular system, including systemic, pulmonary, and coronary vessels, in 10% to 40% of cases. Its prevalence in the United States is probably less than 5 cases per 100,000 people, but it is much more common in Turkey, with an estimated prevalence of 100 cases per 100,000 people. Although Behçet syndrome typically is an adult disease, onset in childhood is well recognized. When the pulmonary artery is affected by Behçet syndrome, the most common lesion is pulmonary artery aneurysm. Other findings include pulmonary artery stenosis and thrombosis, pulmonary infarct, and hemorrhage.21 These lesions are readily evaluated with computed tomography (CT) pulmonary angiography.20 Treatment, as for Takayasu arteritis, is focused on immunosuppression.21 Resolution of aneurysms has been observed after remission of Behçet syndrome.

Malnutrition

Anorexia

Anorexia is a common eating disorder. It is characterized by an intense fear of gaining weight, undue influence of body shape or weight on self-image, the refusal to maintain a body weight of greater than 85% of that predicted, and the absence of at least three consecutive menstrual periods. It is 10 times more common in girls and occurs mostly during adolescence.

Cardiovascular complications occur in up to 80% of patients and are the cause of approximately one third of deaths in this disorder. The most common cardiac abnormality is decreased ventricular wall thickness caused by a loss of cardiac muscle. Other cardiac manifestations include sinus bradycardia, hypotension, arrhythmias, QT interval prolongation, and even sudden death.22 These abnormalities are reversible in the early stages of disease.22,23

Obesity

A worldwide epidemic of obesity is occurring among people of all ages.24 The Obesity Consensus Working Group reported that the prevalence of overweight status has doubled among children 6 to 11 years of age and tripled in those 12 to 17 years of age from 1980 to 2000. Approximately 15% of all 15-year-olds can be classified as obese (defined as a body mass index greater than the 95th percentile) in the United States.

Obesity in children has led to an increase in type 2 diabetes mellitus, hypertension, fatty-related liver disease, and possibly asthma. Heart disease is a significant cause of morbidity in obese persons.24 Excessive adipose accumulation induces increased blood volume and cardiac output, leading to cardiomegaly. Decreased alveolar ventilation and sleep apnea may contribute to both cardiomegaly and pulmonary hypertension (Pickwickian syndrome). Obesity and type 2 diabetes lead to the development of early atherosclerotic disease. It is uncertain whether childhood obesity increases the risk of myocardial infarction or stroke in adulthood.

The high incidence of obesity has led to a corresponding increase in the number of bariatric procedures used to treat patients, including children. Rapid loss of a large amount of weight and decreased absorption of nutrients postoperatively puts individuals at risk for nutritional deficiencies. Beriberi, a disorder of thiamine deficiency, has been reported after gastric bypass surgery.25 The wet form of beriberi is associated with cardiac failure and edema.

Endocrine Disorders

Type 1 Diabetes Mellitus

Gestational Diabetes

Gestational diabetes is associated with congenital abnormalities in infants born to affected mothers. The Baltimore-Washington Infant Study found that maternal diabetes was strongly associated with early cardiovascular malformations and with cardiomyopathy.27 Early cardiovascular malformations refer to defects in early cardiac development such as laterality and cardiac looping defects, outflow tract anomalies with or without transposed great vessels, and atrioventricular septal defects. The data from this study also showed that maternal diabetes was not associated with obstructive and simple shunt defects.

Visceromegaly, hypoglycemia, and cardiomegaly occur commonly in neonates born to diabetic mothers (Fig. 82-6). The severity of these findings and of congenital heart defects may be related to how well the maternal blood sugar was controlled during pregnancy.28 Left ventricular septal wall thickening and hypertrophic subaortic stenosis are characteristic and often transient features in affected neonates (see Fig. 82-6).

Blood Disorders

Sickle Cell Anemia

Imaging: Acute chest syndrome is a common cause of hospitalization, morbidity, and mortality in children with sickle cell disease (Fig. 82-7). Clinical presentation includes chest pain, leukocytosis, and fever. Typical chest radiographic manifestations include cardiomegaly, venous congestion, new radiographic opacity (atelectasis or consolidation), and pleural effusion. The inciting etiology is not always apparent, but possibilities include infection, pulmonary sickling and infarction, and fat emboli from marrow infarction. Infection appears to be a more common underlying factor in younger children, whereas infarction is more common in older persons.

Imaging of the chest in children with sickle cell anemia depends on the clinical scenario. Plain chest radiographs are the mainstay but can be supplemented with echocardiography, CT, MRI, or a nuclear scan for such concerns as bone infarcts or osteomyelitis, pulmonary emboli, complicated pulmonary infection, myocardial ischemia or dysfunction, and liver/myocardial iron overload related to repeated transfusion.30

Children with sickle cell disease and specific risk factors have been shown by de Montalembert and coworkers31 to be at risk for myocardial ischemia. Consequences of ischemia include include chest pain, heart failure, or a ventricular arrhythmia. Thallium-201 single-photon emission CT scans show that almost one third of symptomatic children have a fixed perfusion defect. These perfusion defects may not have a specific vascular pattern, suggesting involvement of the cardiac microcirculation.31

Thalassemia

Cardiac manifestations of thalassemia are primarily due to chronic anemia and vary with the severity of the disease.32 Thalassemia major (homozygous) has more marked hematologic, cardiac, and bone changes than thalassemia minor (heterozygous) and intermedia (the homozygous, milder form). A hyperdynamic circulation and congestive heart failure are the most common clinical cardiac findings.

Cardiomyopathy may develop as a result of ischemia or myocardial iron overload related to chronic transfusion. Widened and coarsely trabeculated rib changes are common in association with red marrow conversion. Extramedullary hematopoiesis occurs commonly in the liver and spleen as well as paraspinal soft tissues, most often in the lower thoracic region, with resultant visceromegaly and paraspinal soft tissue masses. MR imaging is useful for serial follow-up of children who undergo chronic transfusion to assess their visceral and myocardial iron burden and cardiac function (Fig. 82-8).

References

Full references for this chapter can be found on www.expertconsult.com.

References

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