shannon ruzycki university of calgary 3... · vdrl. negative: negative. interferon-gamma release...

Recurrent, refractory cardiac ischemia

SHANNON RUZYCKI

[email protected]

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…


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…


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

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.

http://dx.doi.org/10.1155/2015/634983

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


Valvular disease10-50%

Aortic InsufficiencyPericarditis8%

Pulmonary hypertension

50%

ArteritisSymptomatic 5-20%

Subclinical 60%

Myocarditis50%

Often subclinical


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


Valvular disease25%

Aortic

Pericarditis40%

Arteritis20%

Myocarditis50%

Often subclinical



Recurrent oral aphthaeRecurrent genital aphthae

Anterior/posterior uveitis or retinal vasculitisSkin lesions

Positive pathergy test

Diagnostic Criteria

Cryoglobulinemic Vasculitis


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…


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


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


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


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

shannon ruzycki university of calgary 3... · vdrl. negative: negative. interferon-gamma release...

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