1. THE HEART AND
COLLAGEN VASCULAR
DISORDERS
DR. RAJESH DAS; DM-PDT (1ST YEAR)

2. CARDIOVASCULAR INVOLVEMENT IN:
 SLE.
 APLAS.
 Ankylosing spondylitis.
 Systemic sclerosis.
 Polymyositis & dermatomyositis.
 RA.

3. SYSTEMIC LUPUS ERYTHEMATOSUS

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. 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. 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. 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. 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. 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. VALVULAR DISEASE ASSOCIATED
WITH SLE
Valve masses or Libman-Sacks
vegetation.
Leaflet thickening-
most common echo finding.
Valvular regurgitation.
Valvular stenosis.

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. ANTI PHOSPHOLIPID ANTIBODY SYNDROME

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. 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. 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. 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. SYSTEMIC SCLEROSIS

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. 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. 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. 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. 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. 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. 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. 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. POLYMYOSITIS AND DERMATOMYOSITIS

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. 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. 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. 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. 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. SERONEGATIVE SPONDYLOARTHROPATHIES

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. 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. 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. 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. 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. 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. RHEUMATOID ARTHRITIS

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. THANK YOU