The heart and collagen vascular disorders

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  • SLE is an autoantibody and immune complex disorder, with immunoglobulin and complement deposition in involved organs, including the heart. The serologic findings may be detectable years before clinical disease manifests. However, the view of SLE as only an immune complex disorder is an oversimplification. Some animal models of SLE have been associated with retroviral infections, but there are no consistently demonstrable viral agents in humans with SLE. Studies of twins have suggested a role for genetic factors, and recent data support the involvement of IFN-α in SLE pathogenesis.
  • When effusions occur in the setting of chronic renal failure, it is difficult to distinguish uremic from SLE pericarditis. Pericarditis, as well as tamponade, can occur with drug-induced lupus.
  • Complications of valvularvegetations included cerebral and coronary artery thromboembolism,although the absolute risk is very low
  • Valvulitis (Fig. 89-7), with valve fenestrations and rapidly progressing dysfunction, can occur. The nonbacterial vegetations rarely embolize and cause stroke syndromes. Several studies have demonstrated an increased prevalence of cardiac valve dysfunction in the presence of APLA, with or without SLE.
  • The distinction between atherosclerotic CAD, which is far more common, and coronary arteritis has been inferred from sequential angiographic studies that show more rapid changes in luminal images with arteritis than those characteristic of CAD.
  • Young women with SLE may have several risk factors for coronary atherosclerosis, such as hypertension, which may be secondary to renal disease and diabetes brought about or worsened by corticosteroid exposure. Normal functioning HDL-C has several anti-atherogenic properties. HDL transports excesscholesterol from cells in artery walls to the liver for disposal (10,24), removes reactiveoxygen species from OxLDL, prevents OxLDL-mediated recruitment of inflammatorymediators and monocytes into the vessel wall (25), and inhibits endothelial cell expressionof adhesion molecules (26) and release of chemokines/cytokines (27). Several componentsof HDL contribute to these protective effects, including apoA-1 and the enzymeparaoxonase (28).Conversely, piHDL cannot prevent oxidation of LDL-C and actually increase it, leading toimpairment of reverse cholesterol transport, increased recruitment of monocytes, andprobably an enhanced inflammatory response (11,19). Multiple mechanisms confer proinflammatorycharacteristics on HDL molecules (29). In acute inflammation, hepaticsynthesis of the protective lipoproteins in HDL-C, including apoA-1 and antioxidantenzymes such as PON1, decrease (28). Additionally, protective components in the HDLparticles, such as apoA-1, are partly replaced with pro-oxidant acute phase reactants such asserum amyloid A and ceruloplasmin (29) (30). Furthermore, HDL-C and apoA-1 can bereadily oxidized during periods of inflammation by myeloperoxidase, a product of whiteblood cell activation (30); oxidation of HDL probably contributes to its dysfunction.Oxidized HDL has pro-inflammatory characteristics (29,30), and upregulates the expressionof pro-inflammatory genes such as cyclo-oxygenase-2 (31) and plasminogen activatorinhibitor-1 (32) in endothelial cells.
  • Measurement of troponin I may help in the assessment of cardiac involvement, but the MB fraction of creatine kinase (CK) may be significantly elevated in the presence of skeletal myositis, even in the absence of myocarditis.
  • Measurement of troponin I may help in the assessment of cardiac involvement, but the MB fraction of creatine kinase (CK) may be significantly elevated in the presence of skeletal myositis, even in the absence of myocarditis.
  • However, women with systemic autoimmune diseases known to be associated with this antibody should be screened for its presence prior to pregnancy.
  • However, women with systemic autoimmune diseases known to be associated with this antibody should be screened for its presence prior to pregnancy.
  • 10% to 30% of SLE patients have APLAs.although not all these patients will exhibit the clinical syndrome. Low to moderate levels of APLA can also accompany a number of infectious and other autoimmune diseases, usually without clinical consequence. In the absence of an underlying systemic disease, APLAS is termed primary. The presence of APLA or a lupus anticoagulant, in the absence of sequelae, does not routinely warrant therapy.
  • 10% to 30% of SLE patients have APLAs.although not all these patients will exhibit the clinical syndrome. Low to moderate levels of APLA can also accompany a number of infectious and other autoimmune diseases, usually without clinical consequence. In the absence of an underlying systemic disease, APLAS is termed primary. The presence of APLA or a lupus anticoagulant, in the absence of sequelae, does not routinely warrant therapy.Management of heparin dosing, in the setting of a lupus anticoagulant, which prolongs the baseline partial thromboplastin time (PTT), may require consultation with the coagulation laboratory[41] and use of special assays
  • 10% to 30% of SLE patients have APLAs.although not all these patients will exhibit the clinical syndrome. Low to moderate levels of APLA can also accompany a number of infectious and other autoimmune diseases, usually without clinical consequence. In the absence of an underlying systemic disease, APLAS is termed primary. The presence of APLA or a lupus anticoagulant, in the absence of sequelae, does not routinely warrant therapy.Management of heparin dosing, in the setting of a lupus anticoagulant, which prolongs the baseline partial thromboplastin time (PTT), may require consultation with the coagulation laboratory[41] and use of special assays
  • SLE can involve the heart, as discussed earlier. TTP can cause myocardial ischemia, but not valvular disease; occult neoplasia is associated with nonbacterial thrombotic endocarditis.10% to 30% of SLE patients have APLAs.although not all these patients will exhibit the clinical syndrome. Low to moderate levels of APLA can also accompany a number of infectious and other autoimmune diseases, usually without clinical consequence. In the absence of an underlying systemic disease, APLAS is termed primary. The presence of APLA or a lupus anticoagulant, in the absence of sequelae, does not routinely warrant therapy.Management of heparin dosing, in the setting of a lupus anticoagulant, which prolongs the baseline partial thromboplastin time (PTT), may require consultation with the coagulation laboratory[41] and use of special assays
  • Pathogenesis cause - unknown. An increased frequency of autoimmune disorders and autoantibodies in relatives of patients ->genetic factors. environmental factors. Earliest lesions -> mononuclear infiltrates, primarily T lymphocytes, surrounding small arteries. Endothelial injury and vascular leak -> edema seen in the early stages. Immunocyte and endothelial cell activation yields release of cytokines (e.g., TGF-β, PDGF, IL-4) -> fibroblast production of types I and III collagen and glycosaminoglycans. Over 90% of patients are ANA-positive in both PSS and CREST variant.
  • Generalized PSS is distinguished by proximal cutaneous fibrosis.Thus, the term limited is not meant to indicate the absence of risk of visceral disease, but only refers to the distribution of skin involvement. The pattern of visceral involvement differs somewhat between CREST and PSS..
  • Generalized PSS is distinguished by proximal cutaneous fibrosis.Thus, the term limited is not meant to indicate the absence of risk of visceral disease, but only refers to the distribution of skin involvement. The pattern of visceral involvement differs somewhat between CREST and PSS..
  • In children, there is less sex bias (1 : 1), but when myositis coexists with other autoimmune diseases (e.g., SLE, scleroderma—overlap syndromes), the bias is enhanced (10 : 1 females). When myositis coexists with malignancy in the adult population (mean age, 60 years), it is not sex-biased. Inflammatory myositis can affect patients of all ages. Juvenile dermatomyositis has no association with malignancy, but may be associated with arteritis, which can cause bowel ischemia.Pathogenesis cause unknown. Involved muscles are infiltrated with lymphocytes, and the lymphocyte subsets and histopathologic pattern of inflammation differ between the two disorders. PM is characterized by endomysial mononuclear cell infiltration, although in dermatomyositis there is a greater amount of perivascular inflammation and perifascicular atrophy is seen. Autoantibodies are demonstrable, and certain antibody profiles may be associated with specific clinical patterns of presentation of PM and response to therapy; currently, however, these autoantibodies cannot be used to dictate therapeutic decisions.
  • enthesitis (inflammation at the sites where tendons and ligaments insert onto bones),Although most patients with ankylosing spondylitis will test positive for HLA-B27, it should be noted that the majority of patients with HLA-B27 do not have a spondyloarthropathy.
  • Treatment of the spondyloarthropathies was previously limited to nonsteroidal anti-inflammatories and physical therapy. More recent studies clearly demonstrate the clinical efficacy of TNF inhibitors for treating symptoms of spondylitis. It is unknown whether the TNF inhibitors will ameliorate cardiovascular manifestations of the spondyloarthropathies. Surgery has been successful for managing severe aortic regurgitation in this setting.
  • Pathogenesis: chronic inflammatory infiltrate (T cells, B cells, macrophages, fibroblasts, and mast cells) in the synovial tissues.↑ production of proinflammatory mediators: TNF, IL-1, and IL-6, as well as many chemokines-> stimulate proliferation of synovial fibroblasts, up-regulate expression of adhesion molecules on blood vessels, and promote angiogenesis.
  • RA patients with acute pericarditis are clinically indistinguishable from those with pericardial disease secondary to nonrheumatic conditions. Symptoms of positional chest pain or a pericardial friction rub may be elicited in up to 55% to 65% of patients.6,7 Although in this setting electrocardiograms are often normal, 5% to 10% of patients may manifest abnormalities classically associated with acute pericarditis. Imaging may be useful in confirming the diagnosis of pericarditis. In one series, echocardiography revealed a pericardial effusion in 90% of patients with this clinical diagnosis.6 Aspiration of the pericardial fluid, which is not usually required for diagnosis in the appropriate clinical setting, reveals an elevated white blood cell count, protein, and lactate dehydrogenase; decreased glucose levels; the presence of rheumatoid factor, and a low complement7; these features may help to differentiate it from other causes of pericarditis.
  • Furthermore, some drugs used in the treatment of RA have also been associated with cardiomyopathy, for instance, corticosteroids and anti-malarialscMRI showing delayed enhancement with gadolinium display a characteristic diffuse endocardialhyperenhancement pattern that may suggest cardiac amyloidosis.16
  • Systemic effects of inflammation in rheumatoid arthritis. The rheumatoid joint expresses high levels of various proinflammatory mediators, including tumor necrosis factor (TNF) , interleukin (IL) 1, and IL-6, that amplify the inflammatory response. T helper cells secrete interferon- (IFN-) and IL-17, which in turn activate the cellular constituents of the synovial tissue. These cytokines, which are also found in the vascular endothelium of the atherosclerotic blood vessel, serve to promote coronary artery disease and plaque rupture. Additionally, up-regulation of these cytokines influence other cardiovascular risk factors by affecting skeletal muscle, adipose tissue, and the liver, leading to insulin resistance, dyslipidemia, and increased levels of C-reactive protein (CRP), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1), respectively.
  • There is currently a lack of evidence-based guidelines for the management and prevention of cardiovascular disease in RA patients. In treating RA, the primary goal is tight control of joint inflammation, which is done using conventional disease modifying antirheumatic agents (eg, methotrexate) as well as biologic therapy (eg, TNF inhibitors, tocilizumab, abatacept). TNF inhibitors are generally avoided in RA patients with a history of heart failure because of studies showing increased morbidity and mortality in non-RA patients with congestive heart failure who were treated with a TNF inhibitor.33 In general, traditional cardiovascular risk factors should be aggressively managed in patients with RA until further studies have evaluated the relative benefits and risks of this approach.33
  • The heart and collagen vascular disorders

    1. 1. THE HEART AND COLLAGEN VASCULAR DISORDERS DR. RAJESH DAS; DM-PDT (1ST YEAR)
    2. 2. CARDIOVASCULAR INVOLVEMENT IN:  SLE.  APLAS.  Ankylosing spondylitis.  Systemic sclerosis.  Polymyositis & dermatomyositis.  RA.
    3. 3. SYSTEMIC LUPUS ERYTHEMATOSUS
    4. 4. SYSTEMIC LUPUS ERYTHEMATOSUS  autoimmune multisystem disease.  prevalence 1 in 2,000.  female to male 9 to 1;  peak age 15-40 years.  immune complex deposition, autoantibodies, and ANAs.  photosensitive skin eruptions, serositis, renal, hematological, CNS and CV involvement.
    5. 5. CARDIOVASCULAR INVOLVEMENT  noted in up to 70% of patients by autopsy as well as by echocardiography. • Pericardial disease • Valvular disease • Coronary artery diseases. • Myocardial disease. • Conduction System Disease and arrhythmias.
    6. 6. PERICARDIAL INVOLVEMENT  The most common cardiovascular manifestation of SLE.  Meta-analysis of 26 studies (Mayo Clin Proc 1999;74:255)  Prevalence by Echo : 22 – 54% (Control; 0 – 10%)  may be detected at any point in the disease.  are usually asymptomatic.
    7. 7. PERICARDIAL INVOLVEMENT  may occur as the initial manifestation.  Can occur as a complication of chronic renal disease.  Acute pericarditis → 20% - 30% of pts.  Rarely, may be associated with cardiac tamponade.
    8. 8. PERICARDIAL INVOLVEMENT  chronic pericarditis may occasionally lead to constriction.  It is important to differentiate lupus pericarditis from infectious causes in the setting of concomitant immunosuppressive therapy.  Pericardial fluid  neutrophil predominance,  elevated protein level, and  low or normal glucose concentration.  Low complement level ( non-specific).
    9. 9. PERICARDIAL INVOLVEMENT  Treatment:  depends on its severity.  symptomatic, acute pericarditis:  NSAIDs or corticosteroids.  Acute lupus pericarditis of moderate severity or worse  prednisone - 40 to 60 mg daily f/b a subsequent taper
    10. 10. VALVULAR DISEASE ASSOCIATED WITH SLE Valve masses or Libman-Sacks vegetation. Leaflet thickening- most common echo finding. Valvular regurgitation. Valvular stenosis.
    11. 11. LIBMAN-SACKS VEGETATION  Found in >50% of patients by TEE.  generally localize on the  atrial side of the MV.  arterial side of the AoV.  are usually nonmobile. o < 1 cm2 in size o Irregular borders o Heterogenous echo density o Associated with thickening or regurgitation and less commonly with stenosis.
    12. 12. ABNORMAL LEAFLET THICKENING IN SLE  Mitral and aortic valves.  Generally diffuse but predominant on the mid and tip portions.  Commonly associated with valve regurgitation or valve masses or both.  Valve stenosis is rare (<3%).  Leaflet calcification is uncommon.  Involvement of the annular and subvalvular apparatus is rare (1%).
    13. 13. VALVULAR REGURGITATION IN SLE  Moderate-to-severe regurgitation in 7% to 41%.  MV>TV>AV>PV.  Moderate or severe regurgitation is almost always accompanied by leaflet thickening.
    14. 14. THERAPY OF VALVULAR DISEASE IN SLE  Prosthetic valve replacement or valve repair.  a/w higher morbidity and mortality.  Steroid or cytotoxic therapy has no effect on the presence or the evolution.  Antiplatelet therapy
    15. 15. CORONARY ARTERY DISEASES  Coronary arteritis→ischemic syndromes,  occurs rarely.  Additional causes of ACS in SLE:  thrombosis, often related to the presence of APLAs and,  very rarely, embolism from nonbacterial vegetative endocarditis (Libman-Sacks).  Treatment:  coronary arteritis →high-dose corticosteroids ± cyclophosphamide or azathioprine.  thrombotic disease related to APLAs →long-term anticoagulation.
    16. 16. CORONARY ARTERY DISEASES  Recent data suggest that subclinical atherosclerosis is highly prevalent amongst SLE patients.  Women with SLE between 35-44 years of age are 50 times more likely to have a MI than controls.  pro-inflammatory forms of HDL (piHDL) →increased risk for atherosclerosis.
    17. 17. MYOCARDIAL DISEASE IN SLE  Multifactorial.  result from  immunologic injury,  CAD,  valvular disease, or  coexistent problems such as HTN.  Acute myocarditis  is infrequent,  but can be the initial presentation.  should be suspected in presence of new-onset arrhythmia, fever, dyspnea, and chest pain.  Patients with peripheral skeletal myositis →increased risk for myocarditis.
    18. 18. MYOCARDIAL DISEASE  Noninvasive studies:  abnormal systolic and diastolic function →often reverse with control of disease activity.  Endomyocardial biopsy: Nonspecific→  patches of myocardial fibrosis.  sparse interstitial mononuclear cell infiltrates, and  occasional myocyte necrosis with immune complex deposition.  Treatment:  Unexplained acute LVF→  trial of corticosteroid therapy ± cyclophosphamide or azathioprine. Hydroxychloroquine-induced cardiomyopathy should be considered in patients on this drug.
    19. 19. CONDUCTION SYSTEM DISEASE AND NEONATAL LUPUS  Not expected in adults with SLE.  But seen in infants born to mothers with SLE.  pathogenic mechanism :  transmission of maternal anti-Ro and anti-La ab in utero→myocardial inflammation and fibrosis of the conduction system.  ˂5% of women with these antibodies will give birth to infants with congenital heart block.
    20. 20. CONDUCTION SYSTEM DISEASE AND NEONATAL LUPUS  Screening for antibodies prior to pregnancy is recommended.  If present → serial USG of the fetus to detect fetal conduction abnormality or hydrops.  AV block:  usually appears early in pregnancy  almost always irreversible.  If recognized early→  dexamethasone or  plasma exchange may reverse fetal myocarditis in utero.  Data to support this intervention are limited.
    21. 21. ARRHYTHMIA IN SLE  Sinus tachycardia may be the earliest manifestation of myocarditis.  Atrial fibrillation and flutter may be associated with Pericarditis.  Abnormal heart rate variability may be caused by autonomic dysfunction or occult myocarditis.  Unexplained sinus tachycardia →  in active SLE, even when evidence of cardiac dysfunction is absent .  resolves with treatment of SLE. Occult pulmonary embolism should be considered as a cause of tachycardia, especially in the presence of APLAs.
    22. 22. DRUG-INDUCED LUPUS  Rare complication of certain medications  procainamide,  quinidine, and  hydralazine.  Other medications:isoniazid, minocycline, clindamycin, and phenytoin.  Affects males and females equally.  a/w anti-histone antibodies.
    23. 23. DRUG-INDUCED LUPUS  Common signs and symptoms:  pericarditis,  pleuritis,  arthralgia, and  fever.  Rarely cause renal or neurologic complications.  usually resolve  on its own  after a short course of prednisone and  discontinuation of the offending medication.
    24. 24. ANTI PHOSPHOLIPID ANTIBODY SYNDROME
    25. 25. ANTI PHOSPHOLIPID ANTIBODY SYNDROME  primary or secondary.  characterized by the clinical triad of :  recurrent arterial or venous thrombosis,  pregnancy loss, and  thrombocytopenia.  Serologically  anticardiolipin antibodies,  anti-β 2 glycoprotein antibodies, or  a positive lupus anticoagulant.  hemolytic anemia, and livedo reticularis are commonly present.  In a study by Soltész and colleagues,  Lupus anticoagulant →venous thrombosis,  anticardiolipin antibodies →carotid, peripheral, and coronary artery disease.
    26. 26. ANTIPHOSPHOLIPID ANTIBODY SYNDROME  10% to 30% of SLE pts have APLAs,  although not all these patients will exhibit the clinical syndrome.  Valvular disease →most common CV manifestation (30% of patients):  leaflet thickening,  thrombotic masses extending from the valve ring or leaflets, or  vegetations.  mitral valve > aortic valve  regurgitation >> stenosis .  The first manifestation may be a thromboembolic event (stroke).
    27. 27. ANTIPHOSPHOLIPID ANTIBODY SYNDROME  Primary APLAS is not a/w pericarditis, myocarditis, or conduction disease.  Other CV features:  thrombotic CAD,  intracardiac thrombi, and  nonbacterial endocarditis.  Pulmonary hypertension:  secondary to chronic thromboembolic disease, or  pulmonary arteriolar intimal proliferation.
    28. 28. ANTIPHOSPHOLIPID ANTIBODY SYNDROME  Differential Diagnosis:  SLE,  TTP,  ITP,  occult neoplasia.  Treatment:  clinically significant valvular or intracardiac thrombotic masses :  high-dose anticoagulation with heparin and then  chronic warfarin ± aspirin.  Vegetations may resolve  with anticoagulation therapy over several months, or  spontaneously. ↑ MI and reocclusion following coronary intervention or bypass grafting → Perioperative aggressive prophylactic anticoagulation.
    29. 29. SYSTEMIC SCLEROSIS
    30. 30. SYSTEMIC SCLEROSIS  characterized by:  microvascular occlusive disease, and  excessive fibrotic changes that affects skin and multiple organ systems.  Epidemiology :  rare disease.  Age of onset → 45 - 65 years of age.  Children are infrequently affected.  Among younger individuals, there is a female bias (approx. 7 : 1 vs 3 : 1 for entire scleroderma cohorts).
    31. 31. CLINICAL FEATURES OF SYSTEMIC SCLEROSIS  Raynaud phenomenon:  in > 90% of patients,  usually precedes skin hardening .  arthralgias (>90%),  esophageal dysmotility (>80%),  Telangiectasias:  90% with CREST,  approx. 60% with generalized disease.
    32. 32. CLINICAL FEATURES OF SYSTEMIC SCLEROSIS  pulmonary fibrosis:  35% of CREST,  70% generalized.  Renal crisis:  20-fold more common in generalized disease than in CREST (20% versus 1%).  Calcinosis :  may occur in both subtypes, but  twice as common in the CREST variant (40% versus 20%).
    33. 33. CARDIOVASCULAR INVOLVEMENT IN SYSTEMIC SCLEROSIS  Pericardial involvement:  common in PSS:  fibrinous pericarditis →70% of pts at autopsy.  symptomatic pericarditis:  approx. 16% in diffused.  approx. 30% in limited scleroderma.  Echocardiography:  small pericardial effusions(<40%).  Acute pericarditis syndrome:  large effusions.  may require corticosteroid therapy. (BUT corticosteroids→ scleroderma renal crisis ).
    34. 34. CARDIOVASCULAR INVOLVEMENT IN SYSTEMIC SCLEROSIS  Myocardial Disease:  LV diastolic dysfunction is a frequent manifestation.  but it is rarely severe.  when severe, diastolic dysfunction may worsen PAH.  Epicardial coronary arteries:  generally angiographically normal.  Fixed perfusion defects on nuclear imaging in  80% of PSS and  65% of CREST patients.  MIs can occur with angiographically normal coronary arteries.
    35. 35. CARDIOVASCULAR INVOLVEMENT IN SYSTEMIC SCLEROSIS  Arrhythmias:  The most frequent →PVCs (> 60% )  Transient AF, atrial flutter, and PSVT →20 - 30% of patients.  NSVT in 7% to 13%,  conduction abnormalities:  Ventricular conduction abnormalities (bundle and fascicular blocks) are common .  can be found throughout the conduction system.  sudden death:  in Patients with a history of palpitations or syncope.  risk ↑ in patients with coexistent skeletal myositis.  Primary valvular disease is not common.
    36. 36. CARDIOVASCULAR INVOLVEMENT IN SYSTEMIC SCLEROSIS  Renal crisis→extreme hypertension:  rapidly rising creatinine level,  microangiopathy,  thrombocytopenia, and  left ventricular failure.  Treatment is with ACE inhibitors, and other antiHT,—not with corticosteroids.
    37. 37. CARDIOVASCULAR INVOLVEMENT IN SYSTEMIC SCLEROSIS o PAH: • Primary pulmonary arteriopathy → commonly in limited cutaneous form. • clinically apparent disease in ˂ 10% , • although at autopsy, histopathologic changes of PAH→ 65% -80% of patients. • In comparison to idiopathic PAH: • worse prognosis. (untreated 2-year survival rate as low as 40%). • less favorable outcome with therapy. • Lung /heart lung transplantation is controversial. • Gastrointestinal dysmotility and associated gastroesophageal reflux →aspiration →chronic allograft rejection.
    38. 38. POLYMYOSITIS AND DERMATOMYOSITIS
    39. 39. POLYMYOSITIS AND DERMATOMYOSITIS  Weakness of prox. >distal skeletal muscles.  The CK level is usually ↑.  Respiratory muscles can be clinically involved.  Both conditions can be associated with  fever,  interstitial lung disease, and sometimes  myalgias.
    40. 40. POLYMYOSITIS AND DERMATOMYOSITIS  Dermatomyositis has characteristic skin lesions:  extensor surface and extensor tendon erythema;  Gottron papules overlying the knuckles, elbows, and knees;  edema of the eyelids; and  photosensitive diffuse papular eruption with scaling.  Dermatomyositis → paraneoplastic syndrome (>40 yrs of age).
    41. 41. POLYMYOSITIS AND DERMATOMYOSITIS  Epidemiology  incidence → 2-10 new cases/1,000,000 population annually.  People of all races and ethnicities.  female dominance; F:M=2.5 : 1.  Pathogenesis  cause unknown.  Involved muscles are infiltrated with lymphocytes, and the lymphocyte subsets.
    42. 42. CARDIAC INVOLVEMENT  Pericarditis:  in overlap syndrome.  Cardiomyopathy:  Localized or generalized myocardial dysfunction.  but infrequently causes clinical heart failure.  steroid-responsive.  Corticosteroid myopathy, can mimic PM.  although with a normal CK level,  generally affects skeletal but not respiratory or cardiac muscle.
    43. 43. CARDIAC INVOLVEMENT  conduction system disorders:  conduction block, which can occur in the absence of cardiomyopathy.  Mitral valve prolapse → in up to 50% cases.  Pulmonary hypertension →related to interstitial lung disease.  Acute alveolitis can at times mimic acute heart failure.
    44. 44. SERONEGATIVE SPONDYLOARTHROPATHIES
    45. 45. SERONEGATIVE SPONDYLOARTHROPATHIES  group of multisystem inflammatory diseases sharing common features:  spinal or sacroiliac involvement,  enthesitis  absence of serum rheumatoid factor,  and a high incidence of HLA-B27.  Includes:  ankylosing spondylitis,  reactive arthritis,  psoriatic arthritis, and  IBD–associated arthritis.
    46. 46. SERONEGATIVE SPONDYLOARTHROPATHIES  Among the group of spondyloarthropathies,  ankylosing spondylitis and  reactive arthritis -are the most frequently associated with cardiovascular manifestations.  The two most prevalent cardiovascular manifestations:  conduction system disease and  aortitis, with or without aortic insufficiency.
    47. 47. CONDUCTION SYSTEM DISEASE IN SERONEGATIVE SPONDYLOARTHROPATHIES  presents mainly as heart block,  occurs more commonly in males that are HLA-B27 positive;  often requires permanent pacemaker implantation.  Electrophysiologic studies reveal the block to be at the level of the AV node; it is usually not fascicular.
    48. 48. AORTIC ROOT DISEASE AND VALVE DISEASE IN SERONEGATIVE SPONDYLOARTHROPATHIES  Associated with HLA-B27 in patients with ankylosing spondylitis and reactive arthritis. • Pathology: Inflammation predominantly of the adventitia and intima of the aortic root →  fibroblastic reparative response and  vascularized fibrous tissue thickening. • Aortic valvulitis:  Cusp thickening and retraction.  Thickening of the aorto-mitral junction or subaortic bump.  Proximal aortitis leading to aortic root thickening and dilation.  Aortic and mitral regurgitation.
    49. 49. AORTIC ROOT DISEASE AND VALVE DISEASE IN SERONEGATIVE SPONDYLOARTHROPATHIES • Prevalence  Autopsy studies; 24 to 100%  Echo studies TTE → 8 - 31% TEE → 82% • Echo findings  Nonspecific thickening of aortic and mitral valves  Increased echogenicity of the posterior aortic wall and membraneous interventricular septum  Mild-to-moderate AR.
    50. 50. SERONEGATIVE SPONDYLOARTHROPATHIES  Less common cardiac manifestations:  clinically insignificant diastolic dysfunction,  SVTs, esp. AF,  myocarditis, and  pericarditis.  Treatment:  limited to NSAIDs and physical therapy.  TNF inhibitors:  unknown effect on cardiovascular manifestations.  Surgery:  for managing severe aortic regurgitation.
    51. 51. RHEUMATOID ARTHRITIS
    52. 52. RHEUMATOID ARTHRITIS  Most common of the systemic autoimmune diseases (with a worldwide prevalence of 0.5% to 1%).  female-predominant disease.   characterized by:  chronic symmetrical polyarthritis.  Approx. 3/4th of patients are positive for serum rheumatoid factor or anti-CCP.  Pathogenesis:  chronic inflammatory infiltrate in the synovial tissues.  ↑ production of proinflammatory mediators: TNF, IL-1, and IL-6, as well as many chemokines.
    53. 53. CARDIOVASCULAR MANIFESTATIONS OF RHEUMATOID ARTHRITIS  Pericarditis:  Autopsy studies→ 54% of cases.  Acute, symptomatic pericarditis→ ˂10%of patients with severe RA.  Pericardial effusion→  90% of acute pericarditis cases by echo.  significant pericardial effusion: < 3%.ericardial effusion; < 3%  Aspiration of the pericardial fluid reveals:  ↑ WBC count with neutrophilic predominance, ↑protein, and ↑ LDH;  ↓ glucose levels;  presence of rheumatoid factor (but doesn't confirm the ‘Δ’),  low complement;  Aspiration not usually required for diagnosis in the appropriate clinical setting.
    54. 54. VALVULAR HEART DISEASE ASSOCIATED WITH RHEUMATOID ARTHRITIS  Constrictive pericarditis:  rare  higher mortality rates.  requires an urgent intervention.  must be distinguished from restrictive cardiomyopathy→secondary amyloidosis in patients with long- standing RA.  Clinically significant valvular disease is relatively uncommon.  Valvular diseases:  Valvular thickening  Valvular regurgitation (commonly MR).  Valvular granulomas
    55. 55. Unique to RA Small (<0.5 cm2) Oval in shape Well-defined border Homogenous reflectance Not calcified Usually single VALVULAR NODULES ASSOCIATED WITH RHEUMATOID ARTHRITIS (Cardiol Clin 1998;16;531) (Cardiol Clin
    56. 56. VALVULAR HEART DISEASE ASSOCIATED WITH RHEUMATOID ARTHRITIS  A higher prevalence of valvular disease in pts with:  erosive polyarticular and nodular disease,  systemic vasculitis, and  high titers of RA factor.  Therapy  A few cases of significant improvement of severe valvulitis with the use of steroids or cytotoxic therapy.  Mitral and aortic valve replacement in severe regurgitation.
    57. 57. CARDIOMYOPATHY IN RHEUMATOID ARTHRITIS  characterized by focal granulomatous inflammation of the myocardium.  Granulomas may involve the conduction system → 1°, 2°, or 3° heart block→ usually persists despite immunosuppressive Rx.  3–30% of RA patients in postmortem studies.  Some cases associated with drugs used in RA.  Rarely, may result from secondary amyloidosis.  cMRI may be used to differentiate the different causes of cardiomyopathy.
    58. 58. ARRHYTHMIAS IN RHEUMATOID ARTHRITIS  important cause of mortality in RA.  may be secondary to:  ischaemia,  conduction abnormalities due to rheumatoid nodules,  amyloidosis or  congestive heart failure.  RA patients may have an ↑ sympathetic activity→ ventricular tachy-arrhythmias.  QT-dispersion and corrected QT-dispersion intervals:  significantly longer in RA compared with healthy controls,  related to disease duration.
    59. 59. ACCELERATED CORONARY ARTERY ATHEROSCLEROSIS AND CHF IN RA.  Strong link between RA and accelerated atherosclerosis, highlighting it as an important risk factor for cardiovascular disease.  40% of deaths in RA →cardiovascular disease.  prevalence of cardiovascular disease was comparable to that of pts with diabetes.
    60. 60. ACCELERATED CORONARY ARTERY ATHEROSCLEROSIS IN RA. Atherosclerosis is an inflammatory process driven by many of the same mediators that are associated with rheumatoid inflammation.
    61. 61. ACCELERATED CORONARY ARTERY ATHEROSCLEROSIS AND CHF IN RA.  Additionally, RA appears to be an independent risk factor for multivessel CAD,  Nurses Health Study, women with RA have a two-fold higher rate of myocardial infarctions compared with controls.  RA patients are less likely to be symptomatic from IHD as non-RA controls  twice as likely to have sudden death and unrecognized myocardial infarction.
    62. 62. CHF IN RHEUMATOID ARTHRITIS.  Congestive heart failure →excess cardiovascular mortality in RA.  LV systolic dysfunction was 3 times more common in RA patients compared with the gen. population.  Both RV and LV diastolic dysfunction has been documented.  Mechanisms →unclear.  Less likely to have  a history of ischemic heart disease,  obesity,  or hypertension,  yet they have significantly increased mortality.
    63. 63. MANAGEMENT AND PREVENTION OF CARDIOVASCULAR DISEASE IN RA  There is currently a lack of evidence-based guidelines.  Primary goal is tight control of joint inflammation by using conventional disease modifying antirheumatic agents.  TNF inhibitors are generally avoided in RA patients with a history of heart failure.  studies show ↑ morbidity and mortality in non-RA patients with CHF.  Traditional CV risk factors should be aggressively managed.
    64. 64. THANK YOU

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