OVERVIEW
Nodular disease is a granulomatous inflammatory disease of unknown etiology, mainly invading the lung parenchyma, and involving many organs of the body, such as lymph nodes, skin, joints, liver, kidneys and cardiac tissues, etc. The clinical course is more insidious, and the patient may die suddenly due to complete atrioventricular block and/or congestive heart failure, or even with sudden death as the first symptom.
Etiology
Non-caseating granulomas consist mainly of epithelioid cells, occasionally multinucleated giant cells, surrounded by a few lymphocytes. It is caused by invasion of the heart via hematogenous, lymphogenous and local spread. In advanced cases, the myocardium may be replaced by dense hyaline-like connective tissue. The heart is enlarged, with the conduction system and myocardium predominantly involved, and the aorta, pulmonary arteries, endocardium, or pericardium may be involved in the case of extensive lesions.
Symptoms
1. Systemic manifestations of nodular disease
Nodular disease is a systemic disease, in addition to the heart, other organs, especially the lungs, lymph nodes, skin and so on, can be involved. There may be fever, malaise, anorexia, weight loss, dry cough, croup, dyspnea, maculopapular or papular rash and arthralgia. In addition, the eyes are mostly characterized by inflammation of the uvea; involvement of the conjunctiva, retina, and lacrimal gland may cause visual impairment. When patients with tuberculosis have paratracheal lymph node enlargement and accompanied by some acute peripheral arthritis, uveitis and erythema nodosum lesions, it is called acute tuberculosis or Laeffgren’s syndrome; while those with anterior uveitis accompanied by mumps and facial nerve paralysis are called Heerfordt’s syndrome.
2. Nodular heart disease
The severity of cardiac symptoms depends on the site and extent of granulomatous and scar tissue invasion.
(1) Congestive heart failure Large granulomas infiltrating the myocardium may cause congestive heart failure, and in a few patients, cardiac insufficiency may progressively worsen and lead to death. In addition, it can also be manifested as chronic right heart failure due to extensive lung disease with fibrosis, or chronic left heart failure due to left ventricular systolic and/or diastolic insufficiency caused by myocarditis and myocardial fibrosis.
(2) Arrhythmia can be manifested as bradyarrhythmia or tachyarrhythmia. The former is caused by direct invasion of the sinoatrial node, atrioventricular connective tissue, and bundle branch conduction system by the granuloma. Tachyarrhythmias are predominantly ventricular and can be ventricular pre-systole, often with polygenesis or ventricular tachycardia. Complete atrioventricular block alternates with ventricular tachycardia and can culminate in sudden death. Supraventricular arrhythmias are less common and include atrial pre-systole, paroxysmal atrial tachycardia, atrial flutter, and atrial fibrillation.
(3) Angina pectoris Angina pectoris may occur in patients with tuberous heart disease, and there are reports of patients with typical or atypical angina pectoris, and the chest pain can be partially or completely relieved by nitrate drugs, suggesting that the chest pain may be related to spasmodic ischemia of microvessels.
Examination
1. X-ray chest film
X-ray can show mild to moderate enlargement of the heart or enlargement of the right heart, congestive heart failure, pericardial effusion and left ventricular wall tumor. In addition, enlargement of hilar lymph nodes, infiltration of lung parenchyma, and reticular nodule shadows can be detected, which are important signs of lung tissue involvement.
2. Electrocardiogram
More than half of the patients with nodular disease have abnormal electrocardiograms, including repolarization abnormalities, arrhythmias, and occasionally transmural myocardial infarction-like changes. Patients with confirmed or suspected cardiac nodular disease should routinely undergo 24-hour ambulatory electrocardiography and exercise electrocardiography.
3. Echocardiography
Echocardiography is particularly useful in the diagnosis of ventricular wall tumors, valvular insufficiency, papillary muscle dysfunction leading to mitral valve prolapse, dyskinesia or hypokinesia of the left ventricle or interventricular septum (limited or whole heart), and left ventricular enlargement. Echocardiographic changes in granulomatous lesions and scar formation are echogenic enhancement.
4. Radionuclide myocardial imaging
Thallium 201 (201Tl) imaging shows localized myocardial perfusion defects and/or corresponding ventricular wall segmental motion abnormalities, which can be used to assess the extent of myocardial damage. Nowadays, the clinical application of 201 thallium (201Tl) and 201 gallium (201Ga) myocardial imaging combined examination, especially the use of single photon emission computed tomography (SPECT) method, supplemented by 201 thallium (201Tl) imaging, through the 67 gallium (67Ga) defect area of gallium uptake inversion increased the signs of special changes, can make its specificity significantly improved. In addition, 111 Indium (111In) labeled anti-myosin antibody Fab fragment (AMAAB) imaging and magnetic resonance imaging (MRI) can help establish the diagnosis.
5. Cardiac angiography
Coronary angiography is particularly important in the diagnosis of excluded coronary artery disease. Ventriculography can show changes such as vascular filling defects due to granulomas and ventricular wall motion abnormalities.
6. Endomyocardial biopsy
Endomyocardial biopsy has become the only feasible method to confirm the diagnosis of cardiac sarcoidosis in vivo. However, it is difficult to take accurate samples because granulomas mostly involve the bottom of the left ventricle in a patchy or diffuse form and are unevenly distributed.
7. Electrophysiologic examination
It can be used as an important basis for drug treatment of persistent ventricular arrhythmia caused by cardiac tuberculosis.
8. Other
Kveim test is a skin test, which uses the suspension extracted from spleen or lymph node tissues of patients with tuberculosis as antigen. Clinical application shows that there are few false positives and high specificity. Angiotensin-converting enzyme (ACE) assay is also available. About 81% of patients with active tuberculosis have significantly higher blood ACE levels, which not only helps in diagnosis, but also can be used as a marker for evaluating corticosteroid therapy.
Diagnosis
Chest X-ray and electrocardiogram are helpful for diagnosis. If the diagnosis is difficult, endomyocardial biopsy can be used, but the material taken should be comprehensive. The presence of nodal cardiomyopathy should be considered in young adults with dilated cardiomyopathy or sustained ventricular tachycardia. The diagnostic criteria for cardiac nodal disease according to Fleming’s formulation are: ① There are manifestations of cardiac nodal disease: conduction block; paroxysmal arrhythmia; heart failure; ST-segment and T-wave abnormalities. ② Clinical diagnosis of nodal disease. ③ Histologic confirmation of nodal disease.
Differential diagnosis
This disease needs to be differentiated from idiopathic dilated cardiomyopathy. People with cardiac nodal disease have different clinical manifestations, with a female predominance, a high incidence of severe conduction lesions, abnormal thickening of the ventricular wall, abnormal and variable ventricular wall activity, a pronounced perfusion defect in the anterior interventricular septum and apical region, and a very poor prognosis, all of which are distinct from those with idiopathic dilated cardiomyopathy.
Complications
Arrhythmias, heart failure, sudden death and other complications may occur.
Treatment
1. Corticosteroids
Corticosteroids are the drug of choice, helping to resorb granulomas and preventing their progression to irreversible fibrotic lesions. Improvement in abnormal electrocardiograms, improvement in myocardial diastolic function, relief of myocardial damage, return to normal function of the surviving myocardium, slowing down or elimination of abnormal myocardial perfusion, and gradual normalization of ACE levels have been reported in patients treated with this drug. Prednisone dosage should be 60mg/day initially, tapered over several weeks, and finally maintained at the lowest effective therapeutic dosage administered. It should be taken for a long time and should not be withdrawn at will.
2. Anti-arrhythmic therapy
Nodular disease is often combined with hypercalcemia, and after corticosteroid treatment can lead to hypokalemia, which can aggravate the existing arrhythmia. According to the patient’s condition and the type of arrhythmia, effective antiarrhythmic drugs should be selected to reduce the symptoms and minimize the death rate.
3. Cardiac pacemaker
Patients with complete atrioventricular block and syncope or A.S. syndrome who fail to respond to medication should be implanted with a permanent pacemaker. At the same time, corticosteroids and other related medications should be given. If the patient has persistent ventricular tachyarrhythmia and is at risk of sudden death, an implantable cardioverter defibrillator (ICD) should be placed.
4. Surgery
Surgical removal of ventricular wall tumors can eliminate ventricular arrhythmias. Organ transplantation is contraindicated in patients with systemic nodal disease. Heart transplantation is indicated in young patients with simple cardiac tuberculosis who are severely ill and in end-stage irreversible heart failure.
Prognosis
Ventricular tachyarrhythmias or block and congestive heart failure are the leading causes of death. Early diagnosis and effective treatment are important factors in improving the prognosis of cardiac tachyarrhythmias.