Acute cardiovascular manifestations of immune-mediated systemic inflammatory conditions: clinical biomarkers and immunosuppression
| Cardiovascular manifestation . | Laboratory markers . | Medications/immunosuppression . |
|---|---|---|
| Pericardial disease | hs-CRP, ESR, CBC with differentiala Disease-specific auto-antibodies: •SLE: ANAb, Smith, Ro/La (SSA/SSB), dsDNA, antiphospholipid antibodies+ •RA: RF, anti-CCP •MCTD/SSc: U1RNP, Scl-70, RNA polymerase III, Centromere antibodies or ANA in centromere pattern •EGPA: ANCA, myeloperoxidase, and proteinase 3 antibodies | First-line: high-dose NSAIDs, colchicine 0.6 mg BID •If refractory/recurrent and failed first-line: prednisone 0.2–0.5 mg/kg/day with a slow taper, IL-1 inhibition: anakinra 100 mg daily, rilonacept 320 mg loading × 1, then 160 mg weekly. Autoimmune disease-specific: • methylprednisolone or prednisone 0.5–1 mg/kg, or pulse dose IV steroid for concomitant myocardial involvement or severe cases. • Steroid-sparing options: Azathioprine: start at 50 mg titrate to 1–2 mg/kg daily, MMF: 500 mg PO BID titrate to 1–1.5 g PO BID, IVIG: 2 g/kg over 3–5 days5 *Caution for the use of steroids in SSc with pericarditis |
| Inflammatory cardiomyopathy | hsTnT, NT-proBNP, hsCRP, ESR, CBC with differential Cardiac sarcoidosis: ACE level can be considered, but low sensitivity/specificity | Cardiac sarcoid: prednisone 0.5–1 mg/kg MTX 5–15 mg PO/weekly, or MMF dosing as above. Anti-TNF therapy (infliximab or adalimumab) is used for refractory disease or as steroid-sparing therapy. Giant cell myocarditis: Multidrug immunosuppression, typically high-dose corticosteroids with cyclosporine or tacrolimus. ATG or alemtuzumab for refractory disease. EGPA: High-dose corticosteroids, often with cyclophosphamide, MMF for maintenance therapy. Mepolizumab may be added for eosinophilic mediated manifestations6 |
| Systemic sclerosis (Scleroderma) | Auto-antibodies: RNA polymerase III, Centromere antibodies, or ANA in centromere pattern | Immunosuppression guided by organ manifestations includes MTX, MMF, AZA, and cyclosporine. Steroids are avoided, given the increased risk of precipitating scleroderma renal crisis. SSc Subtype: • SSc-active Raynaud’s, microvascular coronary disease: Amlodipine, Nifedipine +|− long-acting nitrates, Sildenafil • SSc-acute myocarditis: immunosuppressants +|− steroids • Group 1 SSc-PAH: upfront combination therapy (PDE5 + ERA) • Group 2 SSc-PVH: preliminary data for SGLT-2 and MRA in SSc-HFpEF, SSc-HFrEF without inflammation, standard GDMT • Group 3 SSc-ILD-PH: standard immunosuppressant therapy (MMF or cyclophosphamide) +|− biological and antifibrotic therapies |
| Vasculitis | hs-CRP, ESR, CBC with differentiala % Disease-specific antibodies as above plus Immune complex: IgA, anti-GBM, IgG4 level, HLA B51 (Bechet’s), cryoglobulins, complement, RF, hepatitis serologies | General management for most vasculitides includes medium to high-dose corticosteroids as induction therapy with the addition of DMARD/biologic for maintenance as guided by the disease. Disease-specific treatments: • ANCA-associated vasculitis: induction with steroids, cyclophosphamide (15 mg/kg), and rituximab with maintenance regimens defined by subtype.7 • Kawasaki: IVIG 2 g/kg over 3–5 days8 |
| Cardiovascular manifestation . | Laboratory markers . | Medications/immunosuppression . |
|---|---|---|
| Pericardial disease | hs-CRP, ESR, CBC with differentiala Disease-specific auto-antibodies: •SLE: ANAb, Smith, Ro/La (SSA/SSB), dsDNA, antiphospholipid antibodies+ •RA: RF, anti-CCP •MCTD/SSc: U1RNP, Scl-70, RNA polymerase III, Centromere antibodies or ANA in centromere pattern •EGPA: ANCA, myeloperoxidase, and proteinase 3 antibodies | First-line: high-dose NSAIDs, colchicine 0.6 mg BID •If refractory/recurrent and failed first-line: prednisone 0.2–0.5 mg/kg/day with a slow taper, IL-1 inhibition: anakinra 100 mg daily, rilonacept 320 mg loading × 1, then 160 mg weekly. Autoimmune disease-specific: • methylprednisolone or prednisone 0.5–1 mg/kg, or pulse dose IV steroid for concomitant myocardial involvement or severe cases. • Steroid-sparing options: Azathioprine: start at 50 mg titrate to 1–2 mg/kg daily, MMF: 500 mg PO BID titrate to 1–1.5 g PO BID, IVIG: 2 g/kg over 3–5 days5 *Caution for the use of steroids in SSc with pericarditis |
| Inflammatory cardiomyopathy | hsTnT, NT-proBNP, hsCRP, ESR, CBC with differential Cardiac sarcoidosis: ACE level can be considered, but low sensitivity/specificity | Cardiac sarcoid: prednisone 0.5–1 mg/kg MTX 5–15 mg PO/weekly, or MMF dosing as above. Anti-TNF therapy (infliximab or adalimumab) is used for refractory disease or as steroid-sparing therapy. Giant cell myocarditis: Multidrug immunosuppression, typically high-dose corticosteroids with cyclosporine or tacrolimus. ATG or alemtuzumab for refractory disease. EGPA: High-dose corticosteroids, often with cyclophosphamide, MMF for maintenance therapy. Mepolizumab may be added for eosinophilic mediated manifestations6 |
| Systemic sclerosis (Scleroderma) | Auto-antibodies: RNA polymerase III, Centromere antibodies, or ANA in centromere pattern | Immunosuppression guided by organ manifestations includes MTX, MMF, AZA, and cyclosporine. Steroids are avoided, given the increased risk of precipitating scleroderma renal crisis. SSc Subtype: • SSc-active Raynaud’s, microvascular coronary disease: Amlodipine, Nifedipine +|− long-acting nitrates, Sildenafil • SSc-acute myocarditis: immunosuppressants +|− steroids • Group 1 SSc-PAH: upfront combination therapy (PDE5 + ERA) • Group 2 SSc-PVH: preliminary data for SGLT-2 and MRA in SSc-HFpEF, SSc-HFrEF without inflammation, standard GDMT • Group 3 SSc-ILD-PH: standard immunosuppressant therapy (MMF or cyclophosphamide) +|− biological and antifibrotic therapies |
| Vasculitis | hs-CRP, ESR, CBC with differentiala % Disease-specific antibodies as above plus Immune complex: IgA, anti-GBM, IgG4 level, HLA B51 (Bechet’s), cryoglobulins, complement, RF, hepatitis serologies | General management for most vasculitides includes medium to high-dose corticosteroids as induction therapy with the addition of DMARD/biologic for maintenance as guided by the disease. Disease-specific treatments: • ANCA-associated vasculitis: induction with steroids, cyclophosphamide (15 mg/kg), and rituximab with maintenance regimens defined by subtype.7 • Kawasaki: IVIG 2 g/kg over 3–5 days8 |
aAssess for leukopoenia, anaemia, thrombocytopenia, and eosinophilia.
bTiter ≥ 1:80 is considered positive and can be seen in CTD; SSc patients can develop PH across WSPH Group 1–3 classifications.9
ANCA, antineutrophil cytoplasmic antibody; AZA, azathioprine; BID, twice daily; ATG, anti-thymocyte globulin; CBC, complete blood count; CCP, cyclic citrullinated peptide; CRP, C-reactive protein; CTD, connective tissue disease; DMARD, drug modifying anti-rheumatic disease therapy; dsDNA, double-stranded DNA; EGPA, eosinophilic granulomatosis with polyangiitis; ESR, erythrocyte sedimentation rate; ERA, endothelin receptor antagonist; GDMT, goal directed medical therapy; HFpEF, heart failure with preserved ejection fraction; HLA, human leukocyte antigen; ILD, interstitial lung disease; IVIG, intravenous immunoglobulin; MCTD, mixed connective tissue disease; GBM, glomerular basement membrane; MMF, mycophenolate mofetil; MRA, mineralocorticoid receptor antagonist; NSAIDs, non-steroid anti-inflammatory drugs; PAH, pulmonary arterial hypertension; PVH, pulmonary venous hypertension, RA, rheumatoid arthritis; RF, rheumatoid factor; SGLT-2, sodium/glucose cotransporter-2 inhibitor; SLE, systemic lupus erythematosus; SSA/Ro, Sjögren's-syndrome-related type A antigen; SSB/La, Sjögren’s syndrome type B antigen; SSc, systemic sclerosis; ANA, anti-nuclear antibody; TNF, tumor necrosis factor.
Acute cardiovascular manifestations of immune-mediated systemic inflammatory conditions: clinical biomarkers and immunosuppression
| Cardiovascular manifestation . | Laboratory markers . | Medications/immunosuppression . |
|---|---|---|
| Pericardial disease | hs-CRP, ESR, CBC with differentiala Disease-specific auto-antibodies: •SLE: ANAb, Smith, Ro/La (SSA/SSB), dsDNA, antiphospholipid antibodies+ •RA: RF, anti-CCP •MCTD/SSc: U1RNP, Scl-70, RNA polymerase III, Centromere antibodies or ANA in centromere pattern •EGPA: ANCA, myeloperoxidase, and proteinase 3 antibodies | First-line: high-dose NSAIDs, colchicine 0.6 mg BID •If refractory/recurrent and failed first-line: prednisone 0.2–0.5 mg/kg/day with a slow taper, IL-1 inhibition: anakinra 100 mg daily, rilonacept 320 mg loading × 1, then 160 mg weekly. Autoimmune disease-specific: • methylprednisolone or prednisone 0.5–1 mg/kg, or pulse dose IV steroid for concomitant myocardial involvement or severe cases. • Steroid-sparing options: Azathioprine: start at 50 mg titrate to 1–2 mg/kg daily, MMF: 500 mg PO BID titrate to 1–1.5 g PO BID, IVIG: 2 g/kg over 3–5 days5 *Caution for the use of steroids in SSc with pericarditis |
| Inflammatory cardiomyopathy | hsTnT, NT-proBNP, hsCRP, ESR, CBC with differential Cardiac sarcoidosis: ACE level can be considered, but low sensitivity/specificity | Cardiac sarcoid: prednisone 0.5–1 mg/kg MTX 5–15 mg PO/weekly, or MMF dosing as above. Anti-TNF therapy (infliximab or adalimumab) is used for refractory disease or as steroid-sparing therapy. Giant cell myocarditis: Multidrug immunosuppression, typically high-dose corticosteroids with cyclosporine or tacrolimus. ATG or alemtuzumab for refractory disease. EGPA: High-dose corticosteroids, often with cyclophosphamide, MMF for maintenance therapy. Mepolizumab may be added for eosinophilic mediated manifestations6 |
| Systemic sclerosis (Scleroderma) | Auto-antibodies: RNA polymerase III, Centromere antibodies, or ANA in centromere pattern | Immunosuppression guided by organ manifestations includes MTX, MMF, AZA, and cyclosporine. Steroids are avoided, given the increased risk of precipitating scleroderma renal crisis. SSc Subtype: • SSc-active Raynaud’s, microvascular coronary disease: Amlodipine, Nifedipine +|− long-acting nitrates, Sildenafil • SSc-acute myocarditis: immunosuppressants +|− steroids • Group 1 SSc-PAH: upfront combination therapy (PDE5 + ERA) • Group 2 SSc-PVH: preliminary data for SGLT-2 and MRA in SSc-HFpEF, SSc-HFrEF without inflammation, standard GDMT • Group 3 SSc-ILD-PH: standard immunosuppressant therapy (MMF or cyclophosphamide) +|− biological and antifibrotic therapies |
| Vasculitis | hs-CRP, ESR, CBC with differentiala % Disease-specific antibodies as above plus Immune complex: IgA, anti-GBM, IgG4 level, HLA B51 (Bechet’s), cryoglobulins, complement, RF, hepatitis serologies | General management for most vasculitides includes medium to high-dose corticosteroids as induction therapy with the addition of DMARD/biologic for maintenance as guided by the disease. Disease-specific treatments: • ANCA-associated vasculitis: induction with steroids, cyclophosphamide (15 mg/kg), and rituximab with maintenance regimens defined by subtype.7 • Kawasaki: IVIG 2 g/kg over 3–5 days8 |
| Cardiovascular manifestation . | Laboratory markers . | Medications/immunosuppression . |
|---|---|---|
| Pericardial disease | hs-CRP, ESR, CBC with differentiala Disease-specific auto-antibodies: •SLE: ANAb, Smith, Ro/La (SSA/SSB), dsDNA, antiphospholipid antibodies+ •RA: RF, anti-CCP •MCTD/SSc: U1RNP, Scl-70, RNA polymerase III, Centromere antibodies or ANA in centromere pattern •EGPA: ANCA, myeloperoxidase, and proteinase 3 antibodies | First-line: high-dose NSAIDs, colchicine 0.6 mg BID •If refractory/recurrent and failed first-line: prednisone 0.2–0.5 mg/kg/day with a slow taper, IL-1 inhibition: anakinra 100 mg daily, rilonacept 320 mg loading × 1, then 160 mg weekly. Autoimmune disease-specific: • methylprednisolone or prednisone 0.5–1 mg/kg, or pulse dose IV steroid for concomitant myocardial involvement or severe cases. • Steroid-sparing options: Azathioprine: start at 50 mg titrate to 1–2 mg/kg daily, MMF: 500 mg PO BID titrate to 1–1.5 g PO BID, IVIG: 2 g/kg over 3–5 days5 *Caution for the use of steroids in SSc with pericarditis |
| Inflammatory cardiomyopathy | hsTnT, NT-proBNP, hsCRP, ESR, CBC with differential Cardiac sarcoidosis: ACE level can be considered, but low sensitivity/specificity | Cardiac sarcoid: prednisone 0.5–1 mg/kg MTX 5–15 mg PO/weekly, or MMF dosing as above. Anti-TNF therapy (infliximab or adalimumab) is used for refractory disease or as steroid-sparing therapy. Giant cell myocarditis: Multidrug immunosuppression, typically high-dose corticosteroids with cyclosporine or tacrolimus. ATG or alemtuzumab for refractory disease. EGPA: High-dose corticosteroids, often with cyclophosphamide, MMF for maintenance therapy. Mepolizumab may be added for eosinophilic mediated manifestations6 |
| Systemic sclerosis (Scleroderma) | Auto-antibodies: RNA polymerase III, Centromere antibodies, or ANA in centromere pattern | Immunosuppression guided by organ manifestations includes MTX, MMF, AZA, and cyclosporine. Steroids are avoided, given the increased risk of precipitating scleroderma renal crisis. SSc Subtype: • SSc-active Raynaud’s, microvascular coronary disease: Amlodipine, Nifedipine +|− long-acting nitrates, Sildenafil • SSc-acute myocarditis: immunosuppressants +|− steroids • Group 1 SSc-PAH: upfront combination therapy (PDE5 + ERA) • Group 2 SSc-PVH: preliminary data for SGLT-2 and MRA in SSc-HFpEF, SSc-HFrEF without inflammation, standard GDMT • Group 3 SSc-ILD-PH: standard immunosuppressant therapy (MMF or cyclophosphamide) +|− biological and antifibrotic therapies |
| Vasculitis | hs-CRP, ESR, CBC with differentiala % Disease-specific antibodies as above plus Immune complex: IgA, anti-GBM, IgG4 level, HLA B51 (Bechet’s), cryoglobulins, complement, RF, hepatitis serologies | General management for most vasculitides includes medium to high-dose corticosteroids as induction therapy with the addition of DMARD/biologic for maintenance as guided by the disease. Disease-specific treatments: • ANCA-associated vasculitis: induction with steroids, cyclophosphamide (15 mg/kg), and rituximab with maintenance regimens defined by subtype.7 • Kawasaki: IVIG 2 g/kg over 3–5 days8 |
aAssess for leukopoenia, anaemia, thrombocytopenia, and eosinophilia.
bTiter ≥ 1:80 is considered positive and can be seen in CTD; SSc patients can develop PH across WSPH Group 1–3 classifications.9
ANCA, antineutrophil cytoplasmic antibody; AZA, azathioprine; BID, twice daily; ATG, anti-thymocyte globulin; CBC, complete blood count; CCP, cyclic citrullinated peptide; CRP, C-reactive protein; CTD, connective tissue disease; DMARD, drug modifying anti-rheumatic disease therapy; dsDNA, double-stranded DNA; EGPA, eosinophilic granulomatosis with polyangiitis; ESR, erythrocyte sedimentation rate; ERA, endothelin receptor antagonist; GDMT, goal directed medical therapy; HFpEF, heart failure with preserved ejection fraction; HLA, human leukocyte antigen; ILD, interstitial lung disease; IVIG, intravenous immunoglobulin; MCTD, mixed connective tissue disease; GBM, glomerular basement membrane; MMF, mycophenolate mofetil; MRA, mineralocorticoid receptor antagonist; NSAIDs, non-steroid anti-inflammatory drugs; PAH, pulmonary arterial hypertension; PVH, pulmonary venous hypertension, RA, rheumatoid arthritis; RF, rheumatoid factor; SGLT-2, sodium/glucose cotransporter-2 inhibitor; SLE, systemic lupus erythematosus; SSA/Ro, Sjögren's-syndrome-related type A antigen; SSB/La, Sjögren’s syndrome type B antigen; SSc, systemic sclerosis; ANA, anti-nuclear antibody; TNF, tumor necrosis factor.
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