Acute Glomerulonephritis

Clinically evident myocardial involvement is found in 30% to 40% of patients with acute poststreptococcal glomerulonephritis. Pulmonary edema, systemic venous congestion, and cardiomegaly also are common, resulting from salt and water retention. Systemic hypertension, sometimes appearing with hypertensive encephalopathy, is a frequent manifestation and may be responsible for signs of congestive heart failure (CHF) in some, but not all, patients. Although hypertension probably reflects fluid expansion (secondary to impaired salt and water excretion), peripheral resistance has been found to be elevated. Increased renin activity may be responsible for the latter. The acute phase generally resolves within 6 to 8 weeks.

Treatment is directed toward lowering blood pressure and inducing diuresis. Sodium restriction, diuresis usually with intravenous Lasix, and antihypertensive therapy with calcium channel antagonists, vasodilators, or angiotensin-converting enzyme (ACE) inhibitors are standard treatment.

DiGeorge Syndrome

The same syndrome has been described by different researchers in different areas of expertise. Angelo DiGeorge, an endocrinologist, reported DiGeorge syndrome in the 1960s, and Robert Shprintzen, PhD, a speech pathologist, reported velocardiofacial syndrome in the 1970s. A Japanese cardiologist group called it conotruncal anomaly face (CTAF) syndrome in 1978. These syndromes share a common genetic cause in most cases, a chromosome 22q11 deletion; therefore, the term “22q11 deletion syndrome” is currently used. The great majority of patients with these syndromes have serious congenital heart defects (CHDs).

DiGeorge syndrome occurs in both males and females. Clinical features in these syndromes include abnormal facies, CHDs, and absence or hypoplasia of the thymus (with congenital immune deficiency and increased susceptibility to infection) and parathyroid gland (with hypocalcemia). Clinical features of the syndrome are collectively grouped under the acronym of CATCH-22 ( c ardiac, a bnormal facies, t hymic hypoplasia, c left palate, and h ypocalcemia resulting from 22 q11 deletion).

Approximately 90% of patients have a deletion of the long arm of chromosome 22 (22q11.2) detectable with current cytogenetic and fluorescence in situ hybridization (FISH) techniques. In 90% of cases, the disorder occurs as the result of a new mutation. In 10%, the disorder is inherited from a parent in an autosomal dominant fashion. Rarely, the syndrome may be caused by other chromosomal abnormalities or maternal environmental factors (e.g., alcohol, retinoids).

Friedreich’s Ataxia

Friedreich’s ataxia is inherited as an autosomal recessive trait. The onset of ataxia usually occurs before age 10 years, and it progresses slowly, involving the lower extremities to a greater extent than the upper extremities. Explosive dysarthric speech and nystagmus are characteristic, but intelligence is preserved.

Echocardiographic studies reveal evidence of cardiomyopathy in approximately 30% of the cases. Concentric hypertrophy of the left ventricle (LV) with normal LV systolic function is the most common finding. In advanced stages, the LV enlarges, and the LV wall thickness decreases with decreasing fractional shortening, suggesting the presence of fibrosis in the myocardium ( Weidemann et al, 2012 ). Diastolic dysfunction of the LV may be present. The thickness of the interventricular septum correlates well with LV mass determined by magnetic resonance imaging (MRI). Microscopically, diffuse interstitial fibrosis and fatty degeneration of the myocardium, with compensatory hypertrophy of the remaining cells, frequently are found. CHF is the terminal event with most patients dying before 40 years of age.

Cardiac symptoms (e.g., dyspnea, chest pain) are common. Because of physical disability, cardiac problems may not be recognized until arrhythmias or signs of CHF develop. Importantly, there appears to be no clear correlation between the severity of myocardial involvement and that of neurologic dysfunction. A systolic murmur may be audible at the upper left sternal border. Electrocardiographic (ECG) abnormalities are very common. The most common finding is the T-vector change in the limb leads or left precordial leads. Occasionally, left ventricular hypertrophy (LVH), right ventricular hypertrophy (RVH), abnormal Q waves, or short PR interval is found. Chest radiographs usually are normal.

Treatments are the same as those described under different types of cardiomyopathies.

Hyperthyroidism: Congenital and Acquired

The thyroid hormones increase oxygen consumption, stimulate protein synthesis and growth, and affect carbohydrates and lipid metabolism. On the cardiovascular system, the thyroid hormones (1) increase heart rate, cardiac contractility, and cardiac output; (2) increase systolic pressure and decrease diastolic pressure, with mean pressure unchanged; and (3) may increase myocardial sensitivity to catecholamines. Hyperthyroidism results from excess production of triiodothyronine (T ₃ ), thyroxine (T ₄ ), or both.

Congenital hyperthyroidism most often is caused by increased thyroid-stimulating immunoglobulin in infants of mothers who had Graves’ disease during pregnancy. A newborn infant with congenital hyperthyroidism often is premature and usually has a goiter. The baby appears anxious, restless, alert, and irritable. The eyes are widely open and appear exophthalmic.

Juvenile hyperthyroidism is believed to be caused by thyroid-stimulating antibodies and often is associated with lymphocytic thyroiditis and other autoimmune disorders. The incidence of juvenile hyperthyroidism peaks during adolescence, with girls affected more often than boys. These children become hyperactive, irritable, and excitable. The thyroid gland is enlarged.

Both congenital and acquired hyperthyroidism manifests with tachycardia, full and bounding pulses, and increased systolic and pulse pressures. A nonspecific systolic murmur may be audible. Bruits may be audible over the enlarged thyroid in children but not in newborns. In severely affected patients, cardiac enlargement and cardiac failure may develop, requiring prompt recognition and treatment.

Chest radiographs usually are normal but may show cardiomegaly and increased pulmonary vascularity, especially in the presence of heart failure. ECG abnormalities may include sinus tachycardia, peaked P waves, various arrhythmias (supraventricular tachycardia, junctional rhythm), complete heart block, RVH, LVH, or biventricular hypertrophy (but arrhythmias are rare in acquired (juvenile) hyperthyroidism. Echocardiographic studies reveal a hyperkinetic state with increased fractional shortening.

In severely affected patients, a β-adrenergic blocker, such as propranolol, is indicated to reduce the effect of catecholamines. It is interesting to note that some actions of T ₃ on the heart are similar to those of β-adrenergic stimulation and that essentially all beta-blockers can alleviate many of the symptoms of hyperthyroidism. The mechanism of the similarity between these two is unclear; it may involve increased beta-adrenergic receptor density or it may occur independently of β-adrenergic receptor stimulation. Treatment of hyperthyroidism consists of oral administration of antithyroid drugs, propylthiouracil, or methimazole (Tapazole). If CHF develops, treatment with anticongestive medications is indicated (see Chapter 27 ).

Hypothyroidism: Congenital and Acquired

Hypothyroidism results from deficient production of thyroid hormone or a defect in its receptor. The disorder may manifest from birth or may be acquired.

Congenital hypothyroidism, formerly known as cretinism, most often is caused by a developmental defect of the thyroid gland. Hypothyroidism may not be apparent until 3 months of age. The typical picture includes a protuberant tongue, cool and mottled skin, subnormal temperature, carotenemia, and myxedema. Untreated children become mentally retarded and slow in physical development. In the congenital type, patent ductus arteriosus and pulmonary stenosis are frequently found.

The patient may have significant bradycardia, a weak arterial pulse, hypotension, and nonpitting facial and peripheral edema. ECG abnormalities occur in more than 90% of patients and consist of some or all of the following: (1) low QRS voltages, especially in the limb leads; (2) low T-wave amplitude, not affecting the T axis; (3) prolongation of PR and QT intervals; and (4) dome-shaped T wave with an absent ST segment (“mosque” sign) ( Fig. 23-1 ). Echocardiographic studies may show cardiomegaly, pericardial effusion, hypertrophic cardiomyopathy, or asymmetric septal hypertrophy in addition to CHDs, if present. Sodium-l-thyroxine given orally is the treatment of choice.

Tracing from a 3-month-old infant with congenital hypothyroidism. Note low QRS voltages in the limb leads, relatively low T-wave amplitude, and dome-shaped T wave with an absent ST segment in V6.

Acquired (or juvenile) hypothyroidism most often results from lymphocytic thyroiditis (Hashimoto’s disease or autoimmune thyroiditis). Hypothyroidism may result from subtotal or complete thyroidectomy or from protracted ingestion of goitrogens, iodides, or cobalt medications. Rarely, amiodarone can cause hypothyroidism. Serum levels of thyroxine and triiodothyronine are low or borderline.

The heart rate is relatively slow, and the heart sounds may be soft. A weak arterial pulse and hypotension may be present. Myxedema may be present. There is an increased occurrence of hypercholesterolemia. Echocardiographic studies frequently show pericardial effusion and asymmetric septal hypertrophy. The ECG, chest radiograph, and echocardiographic findings of juvenile hypothyroidism are the same as for congenital hypothyroidism. Treatment of hypothyroidism corrects the lipid abnormalities.

Marfan’s Syndrome

Marfan’s syndrome is a generalized connective tissue disease with clinical features involving skeletal, cardiovascular, and ocular systems. It is inherited as an autosomal dominant pattern with variable expressivity.

Skeletal features include tall stature with long slim limbs, little subcutaneous fat and muscle hypotonia, arachnodactyly, joint laxity with scoliosis and kyphosis, pectus excavatum or carinatum, and narrow facies. Eye manifestations may include lens subluxation, increased axial global length, myopia, and retinal detachment.

Clinically evident cardiovascular involvement occurs in more than 50% of patients by the age of 21 years. Microscopic changes probably are present in almost all patients even during infancy and childhood. A wide spectrum of cardiovascular abnormalities is seen in Marfan’s syndrome

• 1.
  

  The common abnormalities include dilatation of the sinus of Valsalva, dilatation of the ascending aorta (with or without dissection or rupture), and aortic regurgitation (AR). Microscopic examination of the proximal aorta (and the proximal coronary arteries) reveals disruption of the elastic media, with fragmentation and disorganization of the elastic fibers. Large accumulations of dermatan sulfate, heparan sulfate, and chondroitin sulfate have been reported in the media of the aorta.

  
  
• 2.
  

  Mitral valve abnormalities are more common in children and young adults than aortic lesions. The mitral valve and left atrial (LA) endocardium often undergo a fibromyxoid degeneration, resulting in dilatation of the mitral valve annulus, mitral regurgitation (MR) and mitral valve prolapse (MVP).

  
  
• 3.
  

  Aneurysm of the pulmonary artery (PA) is less frequently seen.

  
  
• 4.
  

  Rarely, myocardial fibrosis and infarction, rupture of chordae tendineae, aneurysm of the abdominal aorta, and aneurysmal dilatation of the proximal coronary arteries have been reported.

Auscultatory findings of MR and MVP appear in more than 50% of patients (see Chapter 21 ). Rarely, the murmur of AR is audible. The S2 may be accentuated in many patients, especially in those with thin chest walls or dilated PAs. The ECG findings may include LVH; T-wave inversion in leads II, III, aVF, and left precordial leads; and first-degree AV block. Chest radiographs may show cardiomegaly, either generalized or involving only the LV and LA, or a prominence of the ascending aorta, aortic knob, or the main PA segment.

Echocardiographic studies show an increased dimension of the aortic root with or without AR and a “redundant” mitral valve or MVP with thickened valve leaflets and MR. Periodic examination of the aortic root dimension and the status of the MR and MVP are important. As to the diagnosis of MVP in children, however, the adult criteria of MVP are met infrequently, probably because MVP is a progressive disease, and a full manifestation of the disease does not occur until adulthood.

Early death in individuals with this syndrome is most commonly precipitated by aortic dissection, chronic AR, or severe MR. Early and improved surgery and the use of beta-blockers have significantly increased the life expectancy of these patients in recent years.

• 1.
  

  Beta-blockers (atenolol, propranolol) are effective in slowing the rate of aortic dilatation and reducing the development of aortic complications. Recently, enalapril was reported to reduce the rate of increase in the aortic root diameter ( Yetman et al, 2005 ). Thus, beta-blockers or ACE inhibitors (or both) should be administered to children when the aortic root size exceeds the upper limit of normal for age.

  
  
• 2.
  

  Certain physical activities are discouraged to reduce the damage to the aortic root and regurgitant aortic and mitral valves. Exercises, such as weightlifting, rowing, push-ups, pull-ups, sit-ups, and hanging on a monkey bar, should be avoided.

  
  
• 3.
  

  Surgery should be considered when the diameter of the aortic root increases significantly. However, there is controversy as to what is considered significant enlargement of the aortic root to require surgery. Some centers recommend surgery when the aortic root diameter is greater than 3.5 cm ( Kim et al, 2005 ), others recommend surgery when the aortic root equals approximately twice the average measurement for that age group, and still others recommend surgery when the diameter reaches near 6.5 cm ( Gott et al, 1999 ). Recently, a maximum sinus dimension of 5 cm or a rapid increase in dimension (>1 cm/year) have been suggested as indications for surgery ( Tweddell et al, 2012 ). Normal two-dimensional echocardiographic dimensions of the aortic root and the aorta are presented in Table D-3 in Appendix D .

  
  
• 4.
  

  Valve-sparing aortic root reconstruction appears to be preferable to composite graft surgery.

  
  
• 5.
  

  Cardiac failure caused by severe MR is treated with mitral valve repair or valve replacement.

  
  
• 6.
  

  Aortic root dilatation or aortic aneurysm may occur in other connective tissue diseases, and similar surgical procedures may become necessary. The conditions may include, in addition to Marfan’s syndrome, Ehlers-Danlos syndrome, Turner syndrome, Loeys-Dietz syndrome, and others. Dilatation of the ascending aorta or the aortic root can also occur after surgery for CHDs, such as aortic stenosis (AS), TOF, and truncus arteriosus.