Injury and Selected Disease Processes Causing Aortic Root and Aortic Valvular Inflammation

Fig. 4.1

Illustration and aortogram of an aneurysm of the ascending aorta. From Milewicz [5], reprinted with permission from Springer Nature

Aortic valve insufficiency often occurs as the aorta dilates. The risk of the proximal aorta rupturing increases as the size of the aortic root increases. Consideration of prophylactic aortic root replacement is recommended when the diameter reaches 5.0 cm [6, 7]. Once an aneurysm is larger than 6 cm, there is a fourfold increase in the cumulative risk of aortic rupture or dissection [6]. In some cases, surgery may be performed when the aortic diameter is less than 5.0 cm, such as when the aortic diameter increases rapidly (>1 cm/year), when the patient has a family history of premature aortic dissection (dissection occurring when the diameter is <5 cm), and when the patient has moderate-to-severe aortic regurgitation.

Composite valve graft replacement is achieved by mobilizing buttons of aortic tissue around the coronary arteries for anastomosis to the aortic graft. These patients are maintained on beta blockers, and bacterial prophylaxis is recommended. The most common causes of late death after composite valve graft repair are undergoing dental work or invasive diagnostic or surgical procedures and dissection or rupture of the residual distal aorta. Approximately 10% of the patients who undergo composite valve graft repair subsequently require distal aortic surgery.

Other surgical procedures have been developed that preserve the patient’s native aortic valve; these are called “valve-sparing” aortic root replacement procedures [8, 9]. The Yacoub procedure is referred to as the “remodeling” technique and the David procedure is considered the “reimplantation” technique [10, 11]. Both procedures are options for almost all patients with aortic root aneurysms, as long as the aortic valve is structurally normal. In addition, for both techniques, patient survival is excellent, and complications are rare.

Some patients with MFS develop a dissection through the medial layer of the aortic wall. Most of these are type I dissections (DeBakey classification), which also involve the descending thoracic aorta. Dissections involving the ascending aorta can occur in patients who have minimal to no enlargement of the ascending aorta. Most of these dissections occur in the absence of systemic hypertension. Angiography, transesophageal echocardiography, and magnetic resonance imaging are useful techniques for diagnosing aortic dissections. Beta blockers, when tolerated, are used for treatment.

Mitral valve prolapse is present in 70–90% of patients with MFS. Associated mitral regurgitation occurs in up to half of these patients, but serious mitral regurgitation is rare. Mitral valve prolapse can be associated with chest pain and palpitations.

Skeletal and Ocular Manifestations

The skeletal features of the disorder include increased height and arm span; anterior chest wall deformities (pectus excavatum or carinatum); long fingers and toes (arachnodactyly); mild-to-moderate joint laxity; a narrow, highly arched palate and crowding of the frontal teeth; pes planus (flat feet); protrusio acetabuli; and vertebral column abnormalities (scoliosis and thoracic lordosis). The skeletal manifestations of MFS are the most outwardly striking features of the disorder and are often the features that trigger the initial evaluation. Patients usually have a tall stature, primarily due to having long, thin legs, which is reflected in a decreased ratio of the upper body segment (height minus the lower segment) to the lower body segment (top of pubic ramus to the floor). They also generally have an arm span that is greater than their height. The reduced upper-to-lower segment ratio can be further exaggerated by scoliosis and kyphosis.

Marfan syndrome can also affect the eyes. In approximately 50% of the people with MFS, the lenses of the eyes are dislocated (ectopia lentis). Myopia is also common in patients with MFS, but retinal detachment is a rare complication.

Diagnosis

Diagnosing MFS is a complicated clinical decision. The diagnostic criteria for MFS were initially established by an international consortium of clinicians in 1986. The Ghent criteria for diagnosing MFS were introduced in 1996 [12] and revised in 2010 [13]. The 2010 Ghent criteria focus on two cardinal features of MFS: aortic root aneurysm/dissection and ectopia lentis (Table 4.1). The presence of both of these features should be sufficient to diagnosis MFS. When the patient has no family history of MFS and has only one of these features, then the diagnosis is guided by genetic testing results or a “systemic score” that is based on other cardiovascular and ocular manifestations of MFS, as well as findings in other organ systems, such as the skeleton, dura, skin, and lungs (Table 4.2). When the patient has a family history of MFS, then the diagnosis can be made if the patient has one of the two cardinal features of MFS or a high systemic score (i.e., ≥7 points). However, the revised Ghent criteria also provide a caveat regarding the presence of unexpected findings that could be suggestive of an alternative diagnosis, such as Shprintzen-Goldberg syndrome, Loeys-Dietz syndrome, or the vascular form of Ehlers-Danlos syndrome.

Table 4.1

Revised Ghent criteria for diagnosing Marfan syndrome and related conditions

In the absence of family history:

1. Ao (Z ≥ 2) AND EL = MFS^a

2. Ao (Z ≥ 2) AND FBN1 = MFS

3. Ao (Z ≥ 2) AND Syst (≥7 pts) = MFS^a

4. EL AND FBN1 with known Ao = MFS

EL with or without Syst AND with an FBN1 not known with Ao or no FBN1 = ELS

Ao (Z < 2) AND Syst (≥5 with at least one skeletal feature) without EL = MASS

MVP AND Ao (Z < 2) AND Syst (<5) without EL = MVPS

In the presence of family history (FH):

5. EL AND FH of MFS (as defined above) = MFS

6. Syst (≥7 pts) AND FH of MFS (as defined above) = MFS^a

7. Ao (Z ≥ 2 above 20 years old, ≥3 below 20 years) + FH of MFS (as defined above) = MFS^a

Ao aortic diameter at the sinuses of Valsalva above indicated Z-score or aortic root dissection, EL ectopia lentis, ELS ectopia lentis syndrome, FBN1 fibrillin-1 mutation, FBN1 not known with Ao, FBN1 mutation that has not previously been associated with aortic root aneurysm/dissection, FBN1 with known Ao, FBN1 mutation that has been identified in an individual with aortic aneurysm, LDS Loeys-Dietz syndrome, MASS myopia, mitral valve prolapse, borderline (Z < 2) aortic root dilatation, striae, skeletal findings phenotype, MFS Marfan syndrome, MVPS mitral valve prolapse syndrome, SGS Shprintzen-Goldberg syndrome, Syst systemic score, vEDS vascular form of Ehlers-Danlos syndrome, Z Z-score

From Loeys et al. [13]. Reprinted with permission from BMJ Publishing Group Ltd.

^aCaveat: without discriminating features of SGS, LDS, or vEDS AND after TGFBR1/2, collagen biochemistry, COL3A1 testing, if indicated. Other conditions/genes will emerge with time

Table 4.2

Scoring of systemic features of Marfan syndrome

• Wrist AND thumb sign—3 (wrist OR thumb sign—1)

• Pectus carinatum deformity—2 (pectus excavatum or chest asymmetry—1)

• Hindfoot deformity—2 (plain pes planus—1)

• Pneumothorax—2

• Dural ectasia—2

• Protrusio acetabuli—2

• Reduced US/LS AND increased arm/height AND no severe scoliosis—1

• Scoliosis or thoracolumbar kyphosis—1

• Reduced elbow extension—1

• Facial features (3/5)—1 (dolichocephaly, enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia)

• Skin striae

• Myopia >3 diopters—1

• Mitral valve prolapse (all types)—1

Maximum total: 20 points; score ≥7 indicates systemic involvement; US/UL upper segment/lower segment ratio

From Loeys et al. [13]. Reprinted with permission from BMJ Publishing Group Ltd.

Genetic Mutations

It has been clearly established that MFS can be caused by defects in the fibrillin gene (FBN1) on chromosome 15. A number of mutations in FBN1 have been identified in affected individuals and families. An analysis of FBN1 mutations responsible for MFS has indicated that in almost every case, the mutations are private—that is, every family or sporadically affected individual has a different mutation [14]. The majority of mutations are missense mutations that alter a single amino acid. In addition, a second locus for MFS, called the MFS2 locus, has been mapped to 3p24-25 [15]. Furthermore, mutations in transforming growth factor-β (TGF-β) receptor type II (TGFBR2) have recently been described in patients with MFS [16].

Future Therapies

One direction for future therapies will be to prevent the steps that lead from a deficiency in fibrillin-1-containing microfibrils to the aortic wall pathology observed in MFS patients (fragmentation and degradation of the elastic fibers and loss of the smooth muscle cells in the medial layer). Another possible avenue for therapy is based on the findings that fibrillin-1 and microfibrils regulate the TGF-β family of growth factors (cytokines), which influence many aspects of cellular performance, including differentiation, proliferation, protein production, and survival [17].

Relapsing Polychondritis

Relapsing polychondritis is a rare disorder of unknown etiology that is characterized by inflammation and destruction of various cartilaginous structures [18, 19]. Circulating antibodies to type II collagen have been found in some patients [20]. Disease onset is usually in middle age, with men and women showing no difference in age of onset. Bilateral auricular chondritis (Fig. 4.2) is the most common symptom at presentation, followed by laryngotracheal involvement or saddle nose deformity (Fig. 4.3), arthritis, fever, and neurosensory hearing loss [22]. Approximately 15% of patients have systemic vasculitis affecting the medium or large arteries [22], and approximately 24% of patients have cardiovascular complications; the most common of these are aortic regurgitation, followed by mitral regurgitation, pericarditis, and myocardial ischemia [18, 22]. Patients may also develop aortic or large-artery aneurysms, which may thrombose or rupture.

../images/301959_1_En_4_Chapter/301959_1_En_4_Fig2_HTML.png — Fig. 4.2

Inflammation and partial collapse of the auricular cartilage in a patient with relapsing polychondritis. From Arnett and Willerson [21], reprinted with permission from Springer Nature

../images/301959_1_En_4_Chapter/301959_1_En_4_Fig3_HTML.png — Fig. 4.3

Typical “saddle nose” deformity , which is caused by destruction and collapse of the nasal cartilage in patients with Wegener’s granulomatosis or relapsing polychondritis. From Arnett and Willerson [21], reprinted with permission from Springer Nature

The treatment used depends on the disease severity and the organs involved. Corticosteroids are usually required. Immunosuppressive agents may be effective in patients with steroid resistance or intolerance. Cardiac valve replacement is sometimes necessary [22].

Seronegative Spondyloarthritis

Seronegative spondyloarthritis is a group of diseases that includes ankylosing spondylitis, reactive arthritis (formerly called Reiter’s disease), psoriatic arthritis, and the arthritis associated with the idiopathic inflammatory bowel diseases ulcerative colitis and Crohn’s disease [23]. These chronic arthritides are now known to be clinically, epidemiologically, and genetically separate entities; moreover, patients with these conditions do not have rheumatoid factor or antinuclear antibodies (ANAs) .

Joint and Ocular Manifestation

All of these diseases are characterized by a sterile inflammatory process that affects the spinal or peripheral joints, as well as the tendons and ligamentous insertions (enthesitis), which often leads to bony fusion. In ankylosing spondylitis , the axial skeleton is predominantly involved. Joint fusion typically begins in the sacroiliac joints and then progressively ascends into the lumbar, dorsal, and cervical segments, resulting in a rigid and often deformed spine. Radiographs characteristically show sacroiliitis (Fig. 4.4), squaring of the vertebrae, and ossification of the spinal ligaments between the vertebrae (syndesmophytes), giving the spine a “bamboo” appearance (Fig. 4.5). Reactive arthritis and psoriatic arthritis primarily affect the peripheral joints, but similar spinal changes, especially sacroiliitis, occur in 20% of these patients (Fig. 4.6). Peripheral arthritis is a complication in 20% of inflammatory bowel disease cases, and spondylitis is a complication in 10% of these patients. Acute anterior uveitis occurs in approximately 25% of patients with a spondyloarthritis.

../images/301959_1_En_4_Chapter/301959_1_En_4_Fig4_HTML.png — Fig. 4.4

Pelvic radiograph showing bilateral fusion of the sacroiliac joints (sacroiliitis) in a patient with a spondyloarthritis. From Arnett and Willerson [21], reprinted with permission from Springer Nature

../images/301959_1_En_4_Chapter/301959_1_En_4_Fig5_HTML.png — Fig. 4.5

Thoracolumbar radiograph showing calcified ligaments (syndesmophytes) bridging across intervertebral disks of a “bamboo” spine in a patient with ankylosing spondylitis. From Arnett and Willerson [21], reprinted with permission from Springer Nature

../images/301959_1_En_4_Chapter/301959_1_En_4_Fig6_HTML.png — Fig. 4.6

The typical pustular rash (keratoderma blennorrhagica ) of a patient with reactive arthritis . From Arnett and Willerson [21], reprinted with permission from Springer Nature

Cardiac Manifestations

A specific cardiac lesion is found in patients with spondyloarthritides. This lesion is aortic regurgitation, atrioventricular or bundle branch conduction defects, or, rarely, mitral regurgitation (Fig. 4.7) [24–31]. Dilatation and thickening of the walls of the proximal aortic root, especially behind and immediately above the sinus of Valsalva, have been shown histopathologically, along with thickening and shortening of the aortic valve cusps and the development of a fibrous mass (or bump) below the aortic valve (Figs. 4.7 and 4.8) [25–31]. Surrounding the vasa vasorum are collections of plasma cells and lymphocytes [26]. Mitral regurgitation occurs because of a similar fibrous thickening at the basal portion of the anterior mitral leaflet and dilatation of the left ventricle from aortic regurgitation. Bundle branch block and complete heart block occur as the fibrosing process extends from the membranous ventricular septum into the muscular septum, where it interrupts or destroys the conducting fibers in the atrioventricular bundle or proximal bundle branches [26, 32].

../images/301959_1_En_4_Chapter/301959_1_En_4_Fig7_HTML.png — Fig. 4.7

Schematic representation of the typical cardiac lesions of ankylosing spondylitis contrasted with those of rheumatoid arthritis . Ao aorta, AV atrioventricular, LA left atrium, LV left ventricle. From Arnett and Willerson [21], reprinted with permission from Springer Nature

../images/301959_1_En_4_Chapter/301959_1_En_4_Fig8_HTML.png — Fig. 4.8

Necropsy specimens from a patient with ankylosing spondylitis and aortic regurgitation. (a) Gross section through the aortic valve and interventricular septum showing thickening of these structures. (b) Histopathology of the same region showing fibrous thickening. From Arnett and Willerson [21], reprinted with permission from Springer Nature

In approximately 5% of ankylosing spondylitis cases and in rare cases of reactive arthritis, the patient develops spondylitic heart disease [30, 33, 34]. In the reported cases of spondylitic heart disease, HLA-B27 positivity is usually found. This complication usually occurs after many years of having arthritis. First-degree atrioventricular block and aortic regurgitation have been reported in the early stages of the disease [35–37], even before the appearance of arthritis symptoms [35, 37]. Clinically inapparent aortic involvement may be found with echocardiography. Using two-dimensional transthoracic echocardiography, LaBresh et al. [38] found subaortic fibrous ridging or marked valvular leaflet thickening in 11 of 36 men with ankylosing spondylitis or chronic reactive arthritis, but not in any of the 29 normal, age-matched control men. In a study by Arnason et al. [39], transesophageal echocardiography showed aortic valve insufficiency in 10 of 29 men with ankylosing spondylitis, as well as the aortic and valvular thickening seen pathologically. Studies of men who required cardiac pacemakers for complete heart block have shown that these men had high frequencies of underlying spondyloarthritis (often occult) or HLA-B27 positivity. Bergfeldt and colleagues [40, 41] found clinical or radiographic evidence of spondyloarthritis in 28 (12.6%) of 223 men with permanent cardiac pacemakers, 85% of whom were HLA-B27 positive. They also showed that of 83 pacemaker recipients who had no clinical or radiographic stigmata of spondylitis, 17% were HLA-B27 positive, which was a significantly higher frequency than in normal controls (6%) [42]. In another group comprising 91 patients with aortic regurgitation, 15–20% of the patients were found to have B27-associated arthritis [25]. Furthermore, 88% of the male patients who had aortic regurgitation combined with severe conduction system abnormalities were HLA-B27 positive.

Aortic regurgitation and, less often, mitral regurgitation progress relatively rapidly. In most patients with these conditions, prosthetic valve replacement is required in less than 5 years [26, 27, 31, 40]. Patients with complete heart block should receive permanent cardiac pacemakers. There is no evidence that traditional anti-inflammatory or immunosuppressive drugs alter the course of spondylitic heart disease [43].

Rare cardiac features of ankylosing spondylitis and reactive arthritis include pericarditis, myocarditis, and giant cell valvulitis [34, 44]. Several echocardiographic studies have shown global ventricular dysfunction in patients with ankylosing spondylitis, reactive arthritis, or psoriatic arthritis, but the clinical significance of these finding is unclear [45, 46]. However, subtle aortic valve dysfunction may lead to left ventricular dysfunction in these patients [47–49].

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by inflammatory lesions in many organs [50]. The disease occurs in people of any age or race, but young women in the childbearing years are most susceptible, especially Africans, Hispanics, and Asians [51]. Although the etiology of SLE is unknown, SLE is believed to be a complex and heterogeneous disease in which multiple genes (each with modest effects) [52–56] interact with various environment stimuli (e.g., ultraviolet light or viral infections), resulting in apoptosis [55] and acceleration of autoantigen presentation to the immune system [53, 57]. The strongest genetic effects appear to be related to hereditary deficiencies in the complement system and to certain class II HLA genes (HLA-DR2, -DR3, and -DR8 haplotypes) [52, 58].

Autoantibodies

Autoantibodies to intracellular nuclear constituents, such as double-stranded DNA (dsDNA), ribonucleoproteins (including Smith [Sm], RNP, Ro/SSA, and La/SSB), and histones, are characteristically found in SLE patients and account for the positive ANA tests in more than 98% of these patients [52, 59]. Autoantibodies to dsDNA, Sm, and ribosomal P are the most specific for this disease, but they are found in only a minority of the patients. Additional autoantibodies are also common, including those to cellular elements (e.g., red blood cells, lymphocytes, platelets, neurons, and endothelial cells) and plasma components (e.g., IgG, phospholipids, and clotting factors) [59]. Individual patients with SLE have their own distinctive autoantibody profiles, which remain relatively constant over time. Many of these autoantibodies are associated with and probably are the cause of specific clinical manifestations resulting from either the deposition of antigen-antibody immune complexes or antibody-mediated tissue damage. Associations or causal relationships have been established between specific autoantibodies and certain cardiac manifestations. Examples include associations between anti-Ro (SS-A) and La (SS-B) antibodies and congenital heart block [60] and between antiphospholipid antibodies and valvular heart disease (Libman-Sacks endocarditis), other cardiac lesions, and intravascular thromboses [61–63].

Prognosis

The spectrum of SLE effects, including the cardiac manifestations and prognosis of the disease, has changed considerably over the last 50 years [64]. With the advent of more sophisticated serologic tests, it is now possible to diagnose milder cases and those at earlier stages. Treatment with corticosteroids and other immunosuppressive agents, as well as the use of antibiotics, antihypertensives, and other drugs, when appropriate, has improved patient survival from less than 50% at 5 years in the 1950s to more than 90% at 10 years currently [51, 65]. Concomitantly, the prevalence of lupus carditis has decreased markedly; in the precorticosteroid era, lupus carditis was nearly universally present in patients with SLE, especially at autopsy, but the prevalence decreased to 55% in 1954, to 38% in 1971, and to 18% in 1978 [64].

Pathology

Any cardiac structure can be involved in SLE (Table 4.3) [64, 66–69]. However, the presence and extent of the pathologic cardiac lesions correlate poorly with other clinical manifestations. Acute and healed inflammatory lesions have been found scattered focally or diffusely throughout the pericardium, myocardium, valves, and coronary vasculature [64, 70]. Immunofluorescence studies showed extensive granular deposits of immunoglobulins and C3 in the heart, which correlated with the histopathologic changes seen [71]. Therefore, the major cause of lupus carditis is believed to be immune complex-mediated injury, rather than autoantibodies directly targeting cardiac tissues [72]. Another major pathogenetic mechanism is in situ thrombotic events on cardiac valves, other endocardial surfaces, and extracardiac vascular surfaces due to antiphospholipid antibodies [61–63, 73, 74]. There has been increasing evidence that premature atherosclerosis, including coronary atherosclerosis, is a complication of immunologic damage, systemic inflammation, long-term corticosteroid therapy, and other factors [64, 75, 76].

Table 4.3

Cardiac complications of systemic lupus erythematosus

Pericardium	Endocardium	Coronary artery disease	Other
Acute pericarditis supraventricular arrhythmias	Libman-Sacks endocarditis	Premature atherosclerosis	Pulmonary hypertension
Pericardial effusions	Valvular thickening, regurgitation, and/or stenosis	Arteritis	Congenital heart block in fetuses
Pericardial tamponade	Intrachamber thrombi	Thrombosis
Constrictive pericarditis	Aortic arch syndrome
Myocarditis Focal inflammatory lesions (immune complexes) Cardiac “myositis” Diffuse, small-vessel thromboses

From Arnett and Willerson [21], reprinted with permission from Springer Nature

Cardiovascular Manifestations

Pericarditis is the most common cardiac complication in SLE patients, occurring in 19–48% of patients, and is the presenting feature in 1–2% of cases [64, 67, 75]. Clinical features include the typical substernal, position-related, pleuritic chest pain, which is sometimes associated with a pericardial rub and diffuse ST-segment elevation on the electrocardiogram (ECG). Atrial arrhythmias , including flutter and fibrillation, may be found due to the close proximity of the sinoatrial node to the pericardium, whereas ventricular ectopy is rare. Echocardiography often reveals a small pericardial effusion; however, large fluid accumulations with tamponade may occur and can be life threatening (Fig. 4.9). Constrictive pericarditis is rare [77].

../images/301959_1_En_4_Chapter/301959_1_En_4_Fig9_HTML.png — Fig. 4.9

Chest radiographs of a patient with SLE showing massive pericardial effusion and bilateral pleural effusions (a) and complete resolution of the effusions 4 weeks after treatment with corticosteroids (b). From Arnett and Willerson [21], reprinted with permission from Springer Nature

Pericardial fluid from SLE patients shows a mild to moderate inflammatory exudate, is occasionally bloody, has white blood cell counts usually in the 2000–5000/mm³ range, and has a mildly elevated protein level but normal glucose levels. Lupus erythematosus (LE) cells or ANAs may be found in the pericardial fluid of seropositive patients, but these cannot be used to discriminate lupus effusions from those due to other causes. Complement levels are typically low in these patients, and immune complexes have been found [64, 78, 79]. Prompt removal of pericardial fluid may be lifesaving when cardiac tamponade occurs and may be diagnostically necessary when infectious pericarditis is suspected.

The therapy for lupus pericarditis should be determined on the basis of its severity. For mild symptomatic pericarditis, especially that without significant pericardial effusion or other serious disease manifestations, indomethacin (75–150 mg/day, divided into three doses) may be effective. Alternatively, other nonsteroidal anti-inflammatory drugs may be used at doses recommended for arthritis. Some patients, however, require corticosteroids at a low-to-moderate dose (10–40 mg prednisone equivalent per day) to relieve the symptoms or resolve the effusions. Large effusions or pericardial tamponade should result in the prompt administration of high-dose intravenous corticosteroids (60–80 mg prednisone equivalent per day in two divided doses) (Fig. 4.9).

Myocardial involvement is clinically evident in 8–25% of reported series [64, 79, 80]. Several pathologic forms have been recognized, including diffuse small-vessel obliteration and myocyte destruction. They are probably the result of immune complex deposition [64, 81], myocardial cell degeneration and lymphocyte infiltration associated with skeletal myositis, anti-RNP antibodies [82], and global myocardial ischemia and dysfunction or acute myocardial infarction due to coronary artery thrombi associated with antiphospholipid antibodies [62, 83–85].

The earliest clinical manifestations of myocarditis include resting tachycardia, atypical chest discomfort, a third heart sound, and nonspecific ST-T wave changes on ECG. More overt signs include cardiomegaly in the absence of pericardial fluid or other causes of cardiac enlargement, congestive heart failure, and arrhythmias. Troponin levels are elevated. Echocardiography usually reveals multichamber enlargement, global myocardial dyskinesis, and a reduced ejection fraction. Transendocardial biopsy of the myocardium may be necessary to make the diagnosis and to determine the type and activity of the disease process [81]. The differential diagnosis should include secondary causes of myocardial dysfunction, such as hypertension, diabetes mellitus, premature atherosclerotic heart disease, and a rare form of vacuolar cardiomyopathy associated with the use of chloroquine and other antimalarials for treating SLE [86]. Active myocarditis requires aggressive corticosteroid therapy, along with appropriate measures to control arrhythmias and congestive heart failure [62, 66, 79, 80]. Prednisone (60–100 mg/day in two divided doses) should be given immediately, and the patient’s cardiac status should be closely monitored clinically. Congestive heart failure should be treated as necessary with appropriate drugs. Serious atrial and ventricular arrhythmias should be suppressed pharmacologically. Anticoagulation should be used to prevent mural thrombi, especially when antiphospholipid antibodies, which promote intravascular thrombosis, are present. Once the signs of active myocarditis have resolved, the prednisone dose should be tapered slowly over weeks to months, and the patient should be closely monitored (as above) for clinical recurrences.

Premature atherosclerosis is an important cause of morbidity and mortality in SLE patients [76]. There are well-documented cases of SLE patients in their twenties having a myocardial infarction ; often this is seen when the disease onset occurred in childhood [87, 88]. The prevalence of myocardial infarction in SLE patients has ranged from 4% to 45% in multiple series [32, 89–92]. In a case-control study that used electron beam computed tomography to detect coronary artery calcifications, calcifications were found in 33% of the patients younger than 50 years [93].

The cause of premature atherosclerosis in SLE patients is multifactorial (Fig. 4.10). Lupus itself appears to play a major role, the effects of which are mediated by antiphospholipid and other autoantibodies and by endothelial dysfunction. In addition, traditional cardiovascular disease risk factors appear to play a contributing role. Thus, aggressive control of disease activity, along with close monitoring and treatment of elevated low-density lipoprotein levels, hyperglycemia, and hypertension, are essential in the management of SLE [76, 94]. Coronary artery occlusion resulting from an active vasculitis occurs in SLE patients [85, 95]. Coronary arteriography may also prove to be helpful diagnostically when a beaded pattern or small aneurysms are seen in the coronary artery system. Treatment requires high-dose corticosteroids .

../images/301959_1_En_4_Chapter/301959_1_En_4_Fig10_HTML.png — Fig. 4.10

The standard risk factors for atherosclerosis and those specifically related to SLE. The figure shows an arterial wall undergoing plaque formation and calcification and indicates multiple factors that accelerate the atherosclerosis process. *HDL* high-density lipoprotein, *LDL* low-density lipoprotein. From Arnett and Willerson [21], reprinted with permission from Springer Nature

It has been recognized that SLE patients can have spontaneous coronary artery thrombosis secondary to the presence of antiphospholipid antibodies [96, 97]. As with the atheromatous disease, the patient may have no other symptoms of active SLE. A positive test for antiphospholipid antibodies should raise clinical suspicion. Agents to lyse the coronary thrombus should be given promptly, followed by appropriate anticoagulation.

Valvular involvement has long been recognized in SLE patients, especially at autopsy [64]. In 1924, Libman and Sacks [98] first described a sterile verrucous endocarditis that usually affected the underside of the mitral valve leaflets (Fig. 4.11). Necropsy studies have since shown that approximately 43% of lupus patients have Libman-Sacks endocarditis , with the mitral valve being involved in 24% of cases, the aortic valve being involved in 5% of cases, the tricuspid valve being involved in 5% of cases, and the pulmonic valve being involved in 3% of cases [75, 76, 99]. The vegetations usually appear as small, flat or slightly raised projections adhered to the valve margins, commissures of the leaflets, chordae tendineae, and papillary muscles. As shown histologically, the vegetations are composed of lymphocytes, plasma cells, fibrous tissue, fibrin, and platelet thrombi, and hematoxylin bodies are occasionally observed (Fig. 4.11) [75, 99, 100]. The pathological findings associated with these vegetations are thought to be due to the subsequent organization of thrombi on the valve. Ultimately, valvular thickening and fusion of the commissures may lead to either valvular regurgitation or stenosis. Although clinical reports usually describe mitral regurgitation or aortic regurgitation, stenosis of both valves has occurred [94, 101]. Occasionally, emboli to the coronary or cerebral circulations have been reported [94, 102].

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Tags: Valvular Heart Disease

Apr 23, 2020 | Posted by admin in CARDIOLOGY | Comments Off

Thoracic Key

Fastest Thoracic Insight Engine

Injury and Selected Disease Processes Causing Aortic Root and Aortic Valvular Inflammation

Skeletal and Ocular Manifestations

Diagnosis

Genetic Mutations

Future Therapies

Relapsing Polychondritis

Seronegative Spondyloarthritis

Joint and Ocular Manifestation

Cardiac Manifestations

Systemic Lupus Erythematosus

Autoantibodies

Prognosis

Pathology

Cardiovascular Manifestations

Related

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Thoracic Key

Fastest Thoracic Insight Engine

Injury and Selected Disease Processes Causing Aortic Root and Aortic Valvular Inflammation

Skeletal and Ocular Manifestations

Diagnosis

Genetic Mutations

Future Therapies

Relapsing Polychondritis

Seronegative Spondyloarthritis

Joint and Ocular Manifestation

Cardiac Manifestations

Systemic Lupus Erythematosus

Autoantibodies

Prognosis

Pathology

Cardiovascular Manifestations

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