Recurrent, refractory cardiac ischemia
SHANNON RUZYCKI
PGY5 GENERAL INTERNAL MEDICINE
UNIVERSITY OF CALGARY
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The patient presented has consented to share her story.
Case Patient64 year old female presented to emergency with retrosternal chest pain:o Radiating to left arm and jaw o Episodic, lasting between 10-15 minutes o Relieved with nitroglycerin
Case PatientPast medical history:
o Hypothyroid (TSH 5.59 on replacement)o Diabetes (Hb A1C 9.8%)o Hypertension
o 30 pack year smokingo Dyslipidemiao Crohn’s disease (in remission on 5-ASA)
Initial ECG:
Troponin
010203040506070
1:00 12:40
Normal < 15 ng/L
34
58
Hs-T
ropo
nin
ng/L
Time
Admission labwork:Investigation Result Normal
Sodium 134 mmol/L 133-145 mmol/L
Potassium 3.8 mmol/L 3.3-5.1 mmol/L
Creatinine 121 umol/L 40-100 umol/L
Urinalysis Trace blood & leukocytesUrine microscopy No dysmorphic cellsHemoglobin 89 g/L 120-160 g/L
MCV 76 fL 80-100 fL
Platelets 424 x 109/L 150-400 x 109/L
WBCs 11.9 x 109/L 4.0-11.0 x 109/L
CRP 113.4 mg/L < 8.0 mg/L
Investigation Result Normal
Sodium 134 mmol/L 133-145 mmol/L
Potassium 3.8 mmol/L 3.3-5.1 mmol/L
Creatinine 121 umol/L 40-100 umol/L
Urinalysis Trace blood & leukocytesUrine microscopy No dysmorphic cellsHemoglobin 89 g/L 120-160 g/L
MCV 76 fL 80-100 fL
Platelets 424 x 109/L 150-400 x 109/L
WBCs 11.9 x 109/L 4.0-11.0 x 109/L
CRP 113.4 mg/L < 8.0 mg/L
Admission
Diagnosed with NSTEMI
Admitted for medical management
114
Current Presentation:
NSTEMI
First Presented:
NSTEMI
Timeline:
January 11 2017
Troponin
0100200300400500600700
5:56 10:45
Normal < 15 ng/L145
601
Hs-T
ropo
nin
ng/L
Time
Initial angiogram:
LADLCx
RCA
114
Current Presentation:
NSTEMINSTEMIMedical Mx
22
Chest painEmergency
Timeline:
9
114
Admitted:NSTEMI
Medical MxNSTEMI
22
Pericarditis
10
Recurrent chest pain
Timeline:
9
Recurrent chest pain:
Troponin
0
500
1000
1500
2000
14:30 22:00
Normal < 15 ng/L
540
1873
Hs-T
ropo
nin
ng/L
Time
Repeat angiogram:
LAD LCxRCA
Two months
Comparison:
January 2017 March 2017
Rapidly progressing coronary atherosclerosis
Accelerated Atherosclerosis
In-stent thrombosisPost-CABG atherosclerosisHeart transplant recipients
Complex plaque morphologyChronic cocaine abuse
Shah et al. 2015
Secondary Luminal Narrowing
VasculitisRelapsing polychondritisAPLA
VasospasmInfectionsRheumatoid arthritis
Chronic cocaine abuse
Rapidly progressing coronary atherosclerosisAngiographic features of secondary luminal narrowing
Focal artery necrosisArtery wall thickeningArtery wall thinning with aneurysm
Rupture of vessel wall without traumaCoronary artery thrombosis without underlying plaque
Waller et al. 1996
Further work-up…
Investigation Result Normal
Anti-CCP Negative NegativeRheumatoid factor Negative NegativeClinical features of RA NoneAnti-beta 2 glycoprotein Negative NegativeCardiolipin antibodies Negative NegativeLupus type inhibitor N/A On heparinPTT 24.8 seconds 27-37 seconds
Further work-up…Investigation Result Normal
ANCA Negative Negativeanti-MPO antibody < 0.2 AI < 0.2 AIanti-PR3 antibody < 0.2 AI < 0.2 AI
Blood cultures Negative NegativeVDRL Negative NegativeInterferon-gamma release assay Negative Negative
11
Further history…
4
Began feeling “unwell”
Developed anemia of chronic inflammation
and elevated ESR 1510
Negative work-up for temporal arteritis
Has lost 35 lbssince Sept 2016
1
Develops Raynaud’s 22
Develops night sweats
Rapidly progressing coronary atherosclerosis
Accelerated Atherosclerosis
In-stent thrombosisPost-CABG atherosclerosisHeart transplant recipients
Complex plaque morphologyChronic cocaine abuse
Waller et al. 1998; Shah et al. 2015
Secondary Luminal Narrowing
VasculitisRelapsing polychondritisAPLA
VasospasmInfectionsRheumatoid arthritis
Chronic cocaine abuse
Further work-up…
Investigation Result Normal
Ferritin 474 ug/L 13-375 ug/L
ANA Positive, > 1:640Homogeneous pattern
Negative
ESR 111 mm/hr 0-20 mm/hr
Further work-up…CT angiogram: abdominal aorta
Further work-up…CT angiogram: descending aorta
Further work-up…CT angiogram: descending aorta
Vasculitis and the heartAorta
(Large Vessel)
Proximal coronary arteries
(Large Vessel)
Mid-distal coronary arteries
(Medium Vessel)
Microcirculation(Small Vessel)
Pulmonary arteries(Large Vessel)
Coronary arteritis differential
Most common with:
Takayasu’s arteritisPolyarteritis nodosa
Behçet’s diseaseEosinophilic granulomatosis with polyangiitis Miloslavsky & Unizony 2014
1 in 10 patients with vasculitis have cardiac involvement
SLE
Valvular disease50%
Pericarditis15%
ArteritisUsually small vessel
Myocarditis8-25%
Pericardial effusion> 50%
Further work-up…Investigation Result Normal
C3 1.65 g/L 0.60-1.60 g/L
C4 0.28 g/L 0.10-0.40 g/L
Anti-C1q antibody Negative Negative
Anti-Smith antibody Negative Negative
Anti-cellular antibodies Positive, 1:5120 Negative
Anti-histone antibodies High positive Negative
Anti-chromatin antibody High positive Negative
Anti-dsDNA 59 IU/mL < 27 IU/mL
SLE
Malar rash Renal involvementPhotosensitivity Neurologic involvement
Discoid rash Hematologic abnormalitiesOral ulcers Positive ANA
Non-erosive arthritis Positive anti-dsDNA or anti-Sm
Serositis
Diagnostic Criteria
Malar rash Renal involvementPhotosensitivity Neurologic involvement
Discoid rash Hematologic abnormalitiesOral ulcers Positive ANA
Non-erosive arthritis Positive anti-dsDNA or anti-Sm
Serositis
4
Admitted
17
31
10
CABG
Timeline:
Cyclophosphamideand Pulse Steroids 15
29
Final diagnosis:
Coronary arteritis secondary to systemic, large vessel vasculitis secondary to
probable systemic lupus erythematosus
Based on clinical, historical, and laboratory features
No biopsy was obtained
Take home points:
General internists need to recognize uncommon causes of common problems
Acute coronary syndromes can result from non-atherosclerotic luminal narrowing which has a
broad differential diagnosis
Questions & [email protected]
ReferencesBerman M, Paran D, Elkayam O. Cocaine-induced vasculitis. Rambam Maimonides Medical Journal. 2016:7(4);e0036.
Du Toit-Prinsloo L, Saayman G. “Death at the wheel” due to tuberculosis of the myocardium: a cawe report. Cardiovascular Pathology 2016:25(4);271.274.
Gu YL, Svilaas T, van der Horst ICC, Zijlstra F. Conditions mimicking acute ST-segment elevation myocardial infarction in patients referred for primary percutaneous coronary intervention. Netherlands Heart Journal 2008:16(1):325-331.
Hazebrook MR, Kemna MJ, Schalla S, et al. Prevalence and prognostic relevance of cardiac involvement in ANCA-associated vasculitis: eosinophilic granulomatosis with polyangiitis and granulomatosis with polyangiitis. International Journal of Cardiology 2015:199:170-179.
Holt S. Syphilitic ostial occlusion. British Heart Journal 1977:39;469 -470.
Lad SK, Amonkar G. Pancardiac tuberculosis – a case report. Cardiovascular Pathology 2015:25(4);339-340.
Michaud K, Grabherr S, Shiferaw K, et al. Acute coronary syndrome after levamisole-adultered cocaine abuse. Journal of Forensic and Legal Medicine 2014:21;48-52.
Miloslavsky E, Unizony S. The heart in vasculitis. Rheumatic Disease Clinics of North America. 2014:40:11-26.
Ong P, Athanasiadis A, Hill S, et al. Coronary artery spasm as a frequent cause of acute coronary syndrome. Journal of the American College of Cardiology 2008:52(7):523-527.
Shah P, Bajaj S, Virk H, et al. Rapid progression of coronary atherosclerosis: a review. Thrombosis 2015. http://dx.doi.org/10.1155/2015/634983
Shilkin KB. Salmonella typhimurium pancarditis. Postgraduate Medical Journal. 1969:45;40-53.
Waller BF, Fry ETA, Hermiller JB, et al. Nonatherosclerotic causes of coronary artery narrowing – part III. Clinical Cardiology 1996;19;656-661.
Vaidyanathan RK, Byalal JR, Sundaramoorthi T, et al. Rapidly progressive coronary ostial stenosis after aortic valvle replacement in relapsing polychondritis. Journal of Thoracic and Cardiovascular Surgery 2006;131:1395-1396.
Ferritin 474 ug/L 13-375 ug/L
ANA Positive, > 1:640Homogeneous pattern
Negative
ESR 111 mm/hr 0-20 mm/hr
C3 1.65 g/L 0.60-1.60 g/L
C4 0.28 g/L 0.10-0.40 g/L
Glomerular basement membrane Ab < 0.2 AI < 0.9 AI
Anti-CCP Negative Negative
Rheumatoid factor Negative Negative
Anti-C1q antibody Negative Negative
Anti-cellular antibodies Positive, 1:5120 Negative
Lupus panel Negative Negative
Anti-histone antibodies High positive Negative
Relapsing Polychondritis25% have cardiac involvement - AR most common.
Progressive ostial stenosis is rare
Vaidyanathan et al. 2006
Large Vessel: Takayasu arteritis
Common Patient Females aged 10-40 yearsIncidence 1-3 cases per million
Cardiac Involvement 50% of those affected
Large Vessel: Takayasu arteritis
Valvular disease10-50%
Aortic InsufficiencyPericarditis8%
Pulmonary hypertension
50%
ArteritisSymptomatic 5-20%
Subclinical 60%
Myocarditis50%
Often subclinical
Large Vessel: Takayasu arteritis
Miloslavsky & Unizony 2014
Age at onset < 40 yearsClaudication of extremities
Dec’d pulsation of brachial arteriesBlood pressure differential between UEsBruit over subclavian or abdominal aorta
Arteriographic narrowing of aorta or branches
Diagnostic Criteria
Variable Vessels: Behçet’s Disease
Common Patient Females aged 20-40 yearsIncidence 1 cases per 15,000 to 500,000
Cardiac Involvement 6% of those affected
Variable Vessels: Behçet’s Disease
Valvular disease25%
Aortic
Pericarditis40%
Arteritis20%
Myocarditis50%
Often subclinical
Variable Vessels: Behçet’s Disease
Miloslavsky & Unizony 2014
Recurrent oral aphthaeRecurrent genital aphthae
Anterior/posterior uveitis or retinal vasculitisSkin lesions
Positive pathergy test
Diagnostic Criteria
Cryoglobulinemic Vasculitis
Miloslavsky & Unizony 2014
Common Patient Patients with HIV or Hep CIncidence 1 per 100,000
Cardiac Involvement 4-8% of those affected
Small Vessel: Cryoglobulinemic Vasculitis
Pericarditis
Arteritis
Cardiomyopathy
Further work-up…
Investigation Result Normal
HIV serology Negative NegativeCryoglobulins Negative Negative
11
More further history…
4
Began feeling “unwell”
Lab evidence of inflammation
1510
Significant weight loss 1
Raynaud’s 22
Night sweatsSuspected vasculitis
16
MinocyclineRx
Drug-induced SLE
Miloslavsky & Unizony 2014
Common Patient Exposed to a common agentIncidence 15,000 to 30,000 per year in US
Minocycline 1 case per 1,000 exposedCardiac Involvement Unknown
SLE versus Drug-induced SLESLE Variable Drug-induced SLE
Female predominance Gender 1:1Gradual Symptom onset Rapid
20-40 years Age affected AnyRashes likely Cutaneous? Rash unlikely
Possible Raynaud’s? UnlikelyCommon Renal involvement? UncommonPossible Neuro involvement? Uncommon
Common Heme abnormalities? Uncommon
SLE versus Drug-induced SLESLE Drug-induced SLE
Female predominance Gender equityGradual symptom onset Rapid symptom onset
Ages 20-40 years Any ageRashes likely Rash unlikely
Raynaud’s possible Raynaud’s unlikelyRenal involvement common Renal involvement uncommon
Neurologic involvement possible Neuro involvement uncommonHematologic abnormalities
commonHematologic abnormalities uncommon
SLE versus Drug-induced SLE
SLE Drug-induced SLEANA positive ANA positive
Anti-dsDNA positive Anti-dsDNA negativeAnti-Smith positive Anti-Smith negative
Anti-histone positive Anti-histone in 95%Low complement levels Normal complement levels
Small Vessel: ANCA-associated vasculitis
Hazebrook et al. 2015
Miloslavsky & Unizony 2014
Cardiac involvement is most common with EGPA > GPA > MPA
Clinically evident cardiac disease is rare
Screening reveals a prevalence of 50%
Cardiac involvement independently predicts mortality
Small Vessel: Eosinophilic granulomatosis with polyangiitis
Miloslavsky & Unizony 2014
Common Patient Middle aged males or femalesIncidence 20 cases per 1,000,000
Cardiac Involvement 15-60% of those affected
Small Vessel: EGPA
Valvular disease30%
Pericarditis15%
Arteritis3%
Cardiomyopathy30%
Further work-up…CT sinuses
Small Vessel: EGPA
AsthmaEosinophils >10% of WBC
Peripheral neuropathyTransient pulmonary infiltrates
Sinus abnormalitiesPositive biopsy
Diagnostic Criteria
March 31 2017
Date Time Hs-Troponin
Mar 31 2017 23:50 330
Apr 1 2017 5:11 171
Cocaine use and coronary atherosclerosis
Cocaine can accelerate primary atherosclerosis
Cocaine is associated with small vessel midline vasculitis
Levamisole is associated with ANCA-positive vasculitis
Mostly cutaneous and hematologic manifestations
Rare reports of coronary arteritis associated with cocaine-levamisole use
Michaud et al. 2014; Berman et al. 2016
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