Cardiothoracic Manifestations of Connective Tissue Disease
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1 Cardiothoracic Manifestations of Connective Tissue Disease Carole Dennie MD FRCPC Professor of Radiology and Medicine Head, Thoracic and Cardiac Imaging Sections The Ottawa Hospital Co-director Cardiac Radiology and MRI University of Ottawa Heart Institute
2 No financial disclosures Disclosures
3 Objectives To list cardiothoracic manifestations of systemic lupus erythematosus, rheumatoid arthritis and scleroderma To describe recent advanced cardiac MR techniques that show promise in the investigation of patients with connective tissue disorders
4 Introduction Life expectancy lower than general population Primarily due to excess cardiovascular risk Cardiovascular involvement Atherosclerosis and coronary artery disease Myocardial dysfunction and heart failure Pericardial, myocardial and vascular inflammation Thoracic involvement Interstitial lung disease Small airway disease Pleural disease Diaphragmatic dysfunction Thromboembolic disease Pulmonary arterial hypertension
5 Case 1 23 year old man presented to the ED with polymorphic ventricular tachycardia Raynaud s, esophageal dysmotility, digital ulceration in keeping with scleroderma Normal echocardiogram
6 RVEF - 45% (47-74%) RVED cc (55-103) RVSV - 60 cc (32-64) LVEF - 67% (56-78%) LVEDV - 99 cc (47-92) LVSV - 66 cc (32-62) Cardiac MR
7 Single Chamber ICD for Secondary Prevention Patient lost to follow-up
8 Systemic Sclerosis (SSc) Autoimmune disease characterized by vascular dysfunction and multi-organ fibrosis Prevalence = per million yo, : 3-8:1 Thoracic involvement = 90% Cardiovascular involvement = 50% Cardiopulmonary death accounts for 70% of mortality Chifflot H et al. Semin Arthritis Rheum 2008;37:223 Coral-Alvarado P et al. Clin Rheumatol 2009;28(7): Jastrzebska M et al. Cardiology J 2013;20(6):
9 SSc - Cardiovascular Manifestations Diffuse myocardial fibrosis Conduction system abnormalities Valvular disease 10% thickening of leaflets Pericardial disease 20% symptomatic pericarditis (80% autopsy) Premature coronary artery disease Ntusi NAB et al. JCMR 2014;16:21
10 SSc- Pericardial Disease
11 SSc Diffuse Myocardial Fibrosis 37% at autopsy Inflammation and autoimmunity, impairment of microcirculation lead to fibrosis Diastolic and systolic heart failure Ntusi et al 19 asymptomatic SSc vs. 20 controls Higher T1 values, ECV p<0.001 Correlated with disease activity and severity LGE in 53% Impaired peak systolic circumferential strain and peak diastolic strain rate p<0.001 Ntusi NAB et al. JCMR 2014;16:21
12 Diffuse Myocardial Fibrosis LGE Native T1 Map Post-contrast T1 Map (20 minutes) LGE Native T1 Map Post-contrast T1 Map (20 minutes) From Ntusi NAB et al. JCMR 2014;16:21
13 SSc Conduction System Abnormalities 25% develop antibodies to cardiac conducting tissue Sudden death due to ventricular arrhythmia 6-10% More frequent in patients with skeletal muscle involvement KahanA et al. Rheumatolog 2009;48:45-48 Jastrzebska M et al. Cardiol J 2013;20(6):
14 SSc Thoracic Manifestations Interstitial fibrosis 80% NSIP>>UIP Esophageal dysmotility 97% Dilated air-filled esophagus, aspiration Organizing pneumonia Pulmonary arterial hypertension Capobianco J et al. RadioGraphics 2012;32:33-50
15 SSc - NSIP
16 SSc - NSIP
17 SSc Organizing Pneumonia
18 SSc - Pulmonary Arterial Hypertension 10-16% - highest incidence among all CTD Main cause of death 30% of disease related deaths Poorest prognosis, lowest therapeutic response 3 yr mortality = 36-53% 3yr mortality = 61-72% if PAH due to ILD Pulmonary vascular obliteration, pulmonary venoocclusive disease or chronic hypoxemia due to interstitial fibrosis Jastrzebska M et al. Cardiol J 2013;20(6): Mavrogeni S et al. Int J Cardiol 2016;21:
19 SSc Pulmonary Arterial Hypertension
20 SSc Pulmonary Arterial Hypertension
21 SSc Pulmonary Venoocclusive Disease
22 Case 2 37 year-old male, smoker: Sudden shortness of breath, chest pain and palpitations while playing hockey Presented to Emergency Department (ED): Monomorphic ventricular tachycardia: cardioverted in ED ECG: premature ventricular contraction with the same morphology as presenting VT
23 Clinical History Occasional flares of joint pain for 3 years Proximal interpahlangeal, metacarpo-phalangeal joints of hands, knees and ankle joints Lab: Positive rheumatoid factor (titer = 63) Positive anti-cyclic citrullinated peptide (anti-ccp) (titer of 27) C-reactive protein 19.7 Negative ANA, ANCA, hepatitis serology, HIV serology and other viral serology were negative Echocardiogram - normal Coronary angiography - normal
24 Cardiac PET Rubidium Perfusion/ 18 F-FDG
25 b-ssfp CINE SA Function and Volumes Normal Values LV EF 66% % LV EDV ml/m2 LV ESV ml/m2 Courtesy Dr. Joao Inacio RV EV 66% % RV EDV ml/m2 RV ESV ml/m2
26 PSIR SA LGE
27 ICD Implantation for 2 nd Prevention Diagnosis RA myocarditis Typical signs and symptoms of RA within a few months of presentation 4 episodes of non-sustained VT were recorded 1 appropriate shock delivered for VT Left pleural effusion chronic granulomatous pleuritis
28 Rheumatoid Arthritis (RA) Autoimmune condition presenting with symmetric polyarticular arthritis Prevalence = 1-2% yo, : = 3:1 Extraarticular manifestations in 50% Thoracic involvement > 30% Cardiovascular involvement - 60%
29 RA Cardiovascular Manifestations Associated with elevated CRP, ESR, RF, anti-citrullinated protein antibodies and more active or severe RA Life expectancy reduced by 5-10 years 35-50% excess mortality from cardiovascular disease Pericarditis 11-50% (2% symptomatic) Myocarditis very rare Coronary artery disease Heart failure Crowson CS et al. Am Heart J. 2013;166(4):
30 RA Coronary Artery Disease 1.5-2x risk compared to general population Atherosclerotic plaques often clinically silent with increased propensity to rupture Worse outcomes after ACS Mavrogeni S et al. Int J Cardiol 2016;217:
31 RA Heart Failure 2x risk compared to general population esp. RF positive More likely to have preserved ejection fraction Often clinically silent until late in disease Worse prognosis Ntusi NAB et al 39 RA vs. 39 controls Non-ischemic LGE in 41% Focal myocardial edema on T2 weighted (STIR) imaging in 10% Higher native T1 values p=0.03 Expanded ECV p<0.001 Reduced peak systolic circumferential strain and peak diastolic circumferential strain rate p<0.001 Crowson CS et al. Am Heart J. 2013;166(4): Ntusi NAB et al. JACC Cardiovasc Imaging 2015;8(5):
32 RA Diffuse Myocardial Fibrosis LGE Native T1 Map Post-contrast T1 Map ECV = 27.4% ECV = 31.6% ECV =37.9% From Ntusi NAB et al. JACC Cardiovasc Imaging 2015;8(5):
33 RA Thoracic Manifestations Pleural disease Airway disease Interstitial lung disease - 5%, second most common cause of death Necrobiotic nodules Pulmonary arterial hypertension - rare Capobianco J et al. RadioGraphics 2012;32:33-50
34 RA Pleural Disease Pleural effusion /thickening 38-73% Effusion (5%) small, unilateral, resolve spontaneously Pleural thickening up to 50% at autopsy
35 RA - Serositis
36 RA - Airway Disease Bronchiectasis 30% Bronchiolitis obliterans Follicular bronchiolitis
37 RA Follicular Bronchiolitis
38 RA - Bronchiolitis Obliterans Insp Exp
39 RA - Bronchiectasis
40 RA Interstitial Lung Disease Subclinical ILD on HRCT 30% More frequent in males (2:1) Increasing age, smoking and RF are risk factors UIP % NSIP 11-32% Organizing pneumonia Shaw M et al. Eur Resp Rev 2015;24:1-16
41 RA - UIP
42 RA Follicular Bronchiolitis and NSIP
43 RA - Necrobiotic Nodules
44 Case 3 75 year old male presented to ED Increasing shortness of breath and chest pain ESR, CRP >100, +ve ANA, -ve dsdna
45 2 years later - +ve dsdna Diagnosis - SLE Progressed to tamponade required pericardiocentesis x 2
46 Systemic Lupus Erythematosus (SLE) Chronic autoimmune disorder characterized by skin and hematologic manifestations, polyarthritis, renal involvement and serositis Prevalence = 0.1% population yo, : = 6-10:1 Thoracic involvement > 50% Cardiovascular involvement > 50%
47 SLE Cardiovascular Manifestations Antiphospholipid antibodies 30-50% Main risk factor for cardiovascular complications Pericardial effusion/pericarditis Atherosclerosis and coronary artery disease Myocarditis Cardiomyopathy Vasculitis Valvular disease
48 SLE Premature CAD 40 year old female
49 SLE - Pericardial Effusion/Pericarditis 50% asymptomatic Symptomatic pericarditis in 25% May precede clinical signs of SLE or exacerbate underlying disease Tamponade in 2% Constrictive pericarditis - rare Knockaert DC. Eur Heart J 2007;28:
50 SLE - Atherosclerosis and Coronary Artery Disease Premature and accelerated atherosclerosis Risk factors Longer duration of disease, CRP and positive antiphospholipid antibody Risk of ACS in young women with antiphospholipid antibodies - 50x general population Poorer prognosis post-infarct Heart failure 3x more common than age/sex matched controls Mavrogeni S et al. Lupus 2017;28: Toloza SMA et al. Arthritis Rheum 2004;50:
51 SLE - Myocarditis Symptomatic uncommon Clinical detection 3-15% Autopsy up to 50% Mavrogeni et al 20 patients with active SLE vs. 40 patients with suspected IM Only 5/20 SLE suspected of myocarditis 16/20 positive CMR ( T2 and EGE >LGE) Hinojar et al 76 patients with SLE and clinically suspected myocarditis Native T1 and T2 much higher in those with troponin (p<0.01) 71% met diagnostic criteria for acute myocarditis Mavrogeni S et al. Lupus 2013;22:34-43 Hinojar R et al. Int J Cardiol 2016;222:
52 SLE - Valvular Heart Disease Mitral and aortic valve regurgitation secondary to valve thickening 12% Most often asymptomatic Libman-Sachs endocarditis Sterile vegetations - mitral>aortic valves Correlation with disease activity and APS antibody titers
53 SLE - Cardiomyopathy Ischemic and nonischemic Mavrogeni et al. 32 patients with NYHA Class II HF after normal ICA 5/32 impaired LV function without inflammation or LGE 11/32 transmural LV scar (5 inferior, 6 anteroseptal) 9/32 diffuse subendocardial fibrosis positive correlation between LGE and disease activity/duration, blood inflammation indexes and APS antibodies Mavrogeni S et al. Int J Cardiol 2014;176:
54 SLE - Thoracic Manifestations Pleuritis Acute lupus pneumonitis Pulmonary hemorrhage NSIP>>UIP - <5%, usually mild Diaphragmatic dysfunction Thromboembolic disease Pulmonary arterial hypertension
55 SLE - Pleuritis 50% Unilateral or bilateral pleural effusions Most effusions resolve, some residual pleural thickening Most associated with pericardial effusion
56 Acute Lupus Pneumonitis 1-4% established disease Diffuse alveolar damage, necrosis +/- alveolar hemorrhage Mimics pneumonia, infarction, hemorrhage Patch consolidation, usually bilateral Diagnosis of exclusion
57 SLE - Pulmonary Hemorrhage <3%, established disease Rapid onset of dyspnea, fever, hemoptysis Diffuse bilateral groundglass or consolidation Mortality 40-90%
58 SLE Pulmonary Hemorrhage
59 SLE - Diaphragmatic Dysfunction 0.6% Due to myopathy Usually bilateral Shrinking lung syndrome Martens J et al. Chest 1983;84(2):
60 SLE - Pulmonary Arterial Hypertension Second highest prevalence after scleroderma % of patients Due to vasculitis, thrombosis +/- ILD Associated factors Disease duration Raynaud s phenomenon Pleuritis/pericarditis Antiphospholipid antibodies Worse prognosis than other Group 1 PAH but better than scleroderma Tselios K et al. Open Access Rheumatol 2016;Dec 20:1-9 Chung L. et al. Chest 2010;138:
61 Summary Many CTD affect the lungs and heart Cardiac complications are a major cause of mortality Advanced CMR techniques can detect subclinical cardiac involvement
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