Acute Myocardial Acute Myocardial Infarction in the Infarction in the

YoungYoungPresented byPresented by

Glenn Michael L . Gayos M.D.Glenn Michael L . Gayos M.D.

MAKATI MEDICAL CENTERMAKATI MEDICAL CENTERMEDICAL GRAND ROUNDSMEDICAL GRAND ROUNDS

OBJECTIVES:OBJECTIVES:

To present a case of acute To present a case of acute myocardial infarction in the young. myocardial infarction in the young.

To discuss the etiology, approach, To discuss the etiology, approach, management to the young patient management to the young patient with myocardial infarctionwith myocardial infarction

GENERAL DATA:GENERAL DATA:

W.V.W.V.

35 YEAR OLD35 YEAR OLD

MALE MALE

FILIPINOFILIPINO

MARRIEDMARRIED

CHIEF COMPLAINTCHIEF COMPLAINT

CHEST PAINCHEST PAIN

HISTORY OF PRESENT HISTORY OF PRESENT ILLNESSILLNESS::

One week PTAOne week PTA (+) CHEST PAIN(+) CHEST PAIN on the anterior chest on the anterior chest well described as heaviness well described as heaviness with no radiationwith no radiation(+) Self medicated with Aspirin with (+) Self medicated with Aspirin with relief of sxsrelief of sxs

Few Hours PTAFew Hours PTA (+) While watching television, (+) While watching television, Recurrence of Recurrence of CHEST PAINCHEST PAIN on the left on the left anterior chest wall described anterior chest wall described as heaviness with radiation to theas heaviness with radiation to theback. Persisting for more than thirty minutesback. Persisting for more than thirty minutesSeverity of pain 10/10Severity of pain 10/10(+) Difficulty in breathing(+) Difficulty in breathing

PAST MEDICAL PAST MEDICAL HISTORY:HISTORY:

CVD May 2008 (2 weeks PTA )with CVD May 2008 (2 weeks PTA )with right sided residuals, medications right sided residuals, medications prescribed but not takenprescribed but not taken

(-) DM(-) DM (-) HTN(-) HTN (-) allergies(-) allergies (-) CA(-) CA

Family HistoryFamily History Hypertension both sidesHypertension both sides (-) DM, (-) Cancer, (-) Thrombosis, (-) (-) DM, (-) Cancer, (-) Thrombosis, (-)

early stroke or MIearly stroke or MI

Personal Social HistoryPersonal Social History 25 pack year smoking history25 pack year smoking history Occasional alcoholic beverage drinkerOccasional alcoholic beverage drinker Denies history of drug intake or Denies history of drug intake or

stimulantsstimulants

REVIEW OF SYSTEMSREVIEW OF SYSTEMS

(-) headache, (-) loss of (-) headache, (-) loss of consciousnessconsciousness

(-)easy bruisability (-) rashes(-)easy bruisability (-) rashes (-) easy fatigability, (-) palpitations,(-) easy fatigability, (-) palpitations, (-) abdominal pain (-) diarrhea no (-) abdominal pain (-) diarrhea no

constipationconstipation (-) edema (-) rashes (-) caudication(-) edema (-) rashes (-) caudication (-) arthralgia, (-) limitation of motion (-) arthralgia, (-) limitation of motion

Physical Examination on Physical Examination on AdmissionAdmission

Bp 130/80 HR 106 RR 24 Temp 37.5 Bp 130/80 HR 106 RR 24 Temp 37.5 W.T. 55 kg H.T. 163cm BMI 20 JVP 8-9W.T. 55 kg H.T. 163cm BMI 20 JVP 8-9 Conscious coherent in cardio-pulmonary Conscious coherent in cardio-pulmonary

distressdistress Anicteric sclerae, pink palpebral Anicteric sclerae, pink palpebral

conjunctivae no carotid bruits no neck conjunctivae no carotid bruits no neck vein distention no CLADvein distention no CLAD

Equal chest expansion, No retractions, Equal chest expansion, No retractions, Equal fremitus clear breath soundsEqual fremitus clear breath sounds

Physical Examination on Physical Examination on AdmissionAdmission

Adynamic precordium tachycardic Adynamic precordium tachycardic regular rhythm no murmurs distinct regular rhythm no murmurs distinct S1& S2 no S3 notedS1& S2 no S3 noted

Flat soft non-tender abdomenFlat soft non-tender abdomen Full and equal pulses no edema no Full and equal pulses no edema no

cyanosiscyanosis Neuro-examination =shallow Neuro-examination =shallow

nasolabial fold ®, 5/5 motor function nasolabial fold ®, 5/5 motor function on all extremities no sensory deficiton all extremities no sensory deficit

SALIENT FEATURESSALIENT FEATURES

35 year old male35 year old male chest tightness of chest tightness of

more than 30 more than 30 minutes durationminutes duration

DiaphoresisDiaphoresis CVD 2 weeks CVD 2 weeks

PTAPTA Smoker 25 pack Smoker 25 pack

yearsyears

Bp 130/80 HR Bp 130/80 HR 106 RR 24106 RR 24

Equal chest Equal chest expansionexpansion

TachycardicTachycardic Equal PulsesEqual Pulses Shallow Shallow

nasolabial fold Rnasolabial fold R

AT THE EMERGENCY AT THE EMERGENCY ROOMROOM

12 Lead ECG12 Lead ECG, , CChest x rayhest x ray, , serum serum

electrolyteselectrolytes cardiac cardiac

enzymes,enzymes, CBCCBC UrinalysisUrinalysis

NitroglycerineNitroglycerine ISDN dripISDN drip Enoxaparin Enoxaparin MorphineMorphine ASA/ ASA/

Clopidogrel Clopidogrel 02 via nasal 02 via nasal

cannulacannula DiazepamDiazepam

WORKING DIAGNOSISWORKING DIAGNOSIS

S-T elevation Myocardial S-T elevation Myocardial Infarction Anterolateral Wall Infarction Anterolateral Wall

S/P Cerbrovascular DiseaseS/P Cerbrovascular Disease To consider Hypercoagulable To consider Hypercoagulable

StateState

Admitted under Cardiology ServiceAdmitted under Cardiology Service Immediately Referred Patient to Immediately Referred Patient to

interventional cardiology for Primary interventional cardiology for Primary PTCAPTCA

Neuro ReferralNeuro Referral Recommendations: CT ScanRecommendations: CT Scan CVD CVD Infarct notedInfarct noted

REPERFUSIONREPERFUSION

STEMI px presenting to hospital STEMI px presenting to hospital with PCI capability should treat with PCI capability should treat with with primary PCI within 90 primary PCI within 90 mins of medical contactmins of medical contact

Intervention AHA 2007 STEMI ( MODIFIEDAHA 2007 STEMI ( MODIFIEDRECOMMENDATION)CLASS, RECOMMENDATION)CLASS, ASSENT-4 PCI

CATH LAB REPORT OF CATH LAB REPORT OF CORONARY ANGIO AND CORONARY ANGIO AND

PCIPCI Emergency left heart catherization with Emergency left heart catherization with

coronary angiography and percutaneous coronary angiography and percutaneous coronary intervention/stenting of left coronary intervention/stenting of left main coronary artery were done by main coronary artery were done by percutaneous seldinger technique using percutaneous seldinger technique using 6f Judkins catheters via the right femoral 6f Judkins catheters via the right femoral artery with no difficulty or complicationsartery with no difficulty or complications

Coronary Angiography: Coronary Angiography: Totally occluded Left Main Totally occluded Left Main

SegmentSegment

CARDIAC CATHETERIZATION REPORTCARDIAC CATHETERIZATION REPORT

CORONARY ANGIOGRAPHY:CORONARY ANGIOGRAPHY:

Selective cannulation of the LCA with a 6F JL4 catheter shows a Selective cannulation of the LCA with a 6F JL4 catheter shows a TOTALLY TOTALLY OCCLUDED LEFT MAIN SEGMENT.OCCLUDED LEFT MAIN SEGMENT.

Selective cannulation of the RCA with a 6F JR4 cathter shows a very large and dominant Selective cannulation of the RCA with a 6F JR4 cathter shows a very large and dominant vessel with two large patent posterior descending branches.vessel with two large patent posterior descending branches.

PROCEDURE:PROCEDURE: Emergency left heart catheterization with coronary angiography and percutaneous coronary Emergency left heart catheterization with coronary angiography and percutaneous coronary

intervention/ stenting of left main coronary artery were done by percutaneous Seldinger intervention/ stenting of left main coronary artery were done by percutaneous Seldinger technique using 6F Judkins catheter via the right femoral artery with no difficulty or technique using 6F Judkins catheter via the right femoral artery with no difficulty or complications. The patient tolerated the procedure well (IABP was on standby).complications. The patient tolerated the procedure well (IABP was on standby).

CATHETERS USED: CATHETERS USED: 6 F JL4 AND JR4 Cordis diagnostic catheters6 F JL4 AND JR4 Cordis diagnostic catheters6F XB 3.5 Cordis Vistabrite tip guide catheter6F XB 3.5 Cordis Vistabrite tip guide catheter

CONTRAST USED:CONTRAST USED:130 ML Ultravist 370130 ML Ultravist 370

PCIPCIA 6F XB 3.5 Cordis Vistabrite tip guiding catheter was used to engage the left A 6F XB 3.5 Cordis Vistabrite tip guiding catheter was used to engage the left

main. A 0.014” x 180 cm Cordis Supersoft Stabilitzer wire was used to main. A 0.014” x 180 cm Cordis Supersoft Stabilitzer wire was used to cross the lesion and positioned into the distal LAD. A 2.0 (15 mm length) cross the lesion and positioned into the distal LAD. A 2.0 (15 mm length) Terumo Ryujin rapid exchange balloon was then advanced across the lesion Terumo Ryujin rapid exchange balloon was then advanced across the lesion and then inflated at 12 atm for 23 seconds. A second balloon 3.0 x 15 mm and then inflated at 12 atm for 23 seconds. A second balloon 3.0 x 15 mm Sprinter was used to further dilate the lesion at 12-14 atm for 11-33 Sprinter was used to further dilate the lesion at 12-14 atm for 11-33 seconds. Post balloon angiogram showed a residual stenosis of 40 – 50%.seconds. Post balloon angiogram showed a residual stenosis of 40 – 50%.

A Taxus 3.5 x 20 mm stent was then advanced across the lesion and deployed A Taxus 3.5 x 20 mm stent was then advanced across the lesion and deployed at 8 atm for 36 seconds. The delivery balloon was re-inflated at 14 atm for at 8 atm for 36 seconds. The delivery balloon was re-inflated at 14 atm for 13 seconds. Post-stent angiogram of the left main LAD showed no 13 seconds. Post-stent angiogram of the left main LAD showed no significant residual stenosis at the lesion site with TIMI-2 antegrade distal significant residual stenosis at the lesion site with TIMI-2 antegrade distal flow, no contrast staining and no loss of side branches. No significant flow, no contrast staining and no loss of side branches. No significant change in the post-stenting angiographic results occurred after an change in the post-stenting angiographic results occurred after an observation period of 5 – 7 minutes. The procedure was terminated with the observation period of 5 – 7 minutes. The procedure was terminated with the patient in stable condition. patient in stable condition.

CARDIAC CATHETERIZATION REPORTCARDIAC CATHETERIZATION REPORT

BALLOON INFLATIONBALLOON INFLATION

Lesion dilated: Left main-proximal LADLesion dilated: Left main-proximal LAD

SITESITE Balloon/ Balloon/ StentStent

SizeSize DurationDuration

(sec)(sec)Pressure Pressure

(atm)(atm)

Left Main Left Main LADLAD

Ryujin Ryujin balloonballoon

2.0 x 15 mm2.0 x 15 mm 2323 1212

Sprinter Sprinter balloonballoon

3.0 x 15 mm3.0 x 15 mm 1111

33331212

1414

Taxus stentTaxus stent 3.5 x 20 mm3.5 x 20 mm 3636 88

Delivery Delivery balloonballoon

1313 1414

PTCA CONCLUSIONPTCA CONCLUSION

Successful Primary PCI/stent deployment of Successful Primary PCI/stent deployment of the Left Main - LADthe Left Main - LAD

Total Occlusion of Left Total Occlusion of Left Main Coronary ArteryMain Coronary Artery

Rare occurrence with 2.6% frequency in Rare occurrence with 2.6% frequency in one study one study

Generally presents as pulmonary edema, Generally presents as pulmonary edema, cardiogenic shock, or sudden death cardiogenic shock, or sudden death

PTCA feasible and effective procedure PTCA feasible and effective procedure

Effect of Primary Angioplasty on Total or Subtotal Left Main OcclusionEffect of Primary Angioplasty on Total or Subtotal Left Main Occlusion Analysis of Incidence, Clinical Features, Outcomes, and Prognostic Determinants Analysis of Incidence, Clinical Features, Outcomes, and Prognostic Determinants Hon-Kan Yip, MD; Chiung-Jen Wu, MD; Mien-Cheng Chen, MD; Hsueh-Wen Chang, Hon-Kan Yip, MD; Chiung-Jen Wu, MD; Mien-Cheng Chen, MD; Hsueh-Wen Chang,

PhD; Kelvin Yuan-Kai Hsieh, MD; Chi-Ling Hang, MD and Morgan Fu, MD PhD; Kelvin Yuan-Kai Hsieh, MD; Chi-Ling Hang, MD and Morgan Fu, MD

POST PTCAPOST PTCA

30 minutes Post PTCA 30 minutes Post PTCA Patient had episodes of desaturationPatient had episodes of desaturation O2 inhalation increased to fio2 100 % O2 inhalation increased to fio2 100 %

(02 sat 80-90%)(02 sat 80-90%) Patient intubatedPatient intubated Pulmo referral donePulmo referral done CXR post intubation revealed pulmonary CXR post intubation revealed pulmonary

congestion/ pulmonary edemacongestion/ pulmonary edema ABGABG done done

CHEST X-RAYCHEST X-RAY (POST INTUBATION)(POST INTUBATION)

BASELINE CXRAYCXRAY AFTER

< 6 HOURS

AT THE TELEMETRYAT THE TELEMETRY

Episodes of non-sustained ventricular Episodes of non-sustained ventricular tachycardiatachycardia Patient started on AMIODARONE for Post PTCA arrythmia Patient started on AMIODARONE for Post PTCA arrythmia

INITIAL LOADING DOSE (150 mg)INITIAL LOADING DOSE (150 mg) MAINTENANCE DRIP (900 mg x 24 hours)MAINTENANCE DRIP (900 mg x 24 hours)

Patient admitted to Telemetry UnitPatient admitted to Telemetry Unit Referral to Nephrology Service for renal Referral to Nephrology Service for renal

prophylaxsis and decreased urine outputprophylaxsis and decreased urine output CT angiography with renal prophylaxis doneCT angiography with renal prophylaxis done D-dimer D-dimer 642.60 ng/ ml (<500 ng/ ml)642.60 ng/ ml (<500 ng/ ml)

2D ECHOCARDIOGRAM 2D ECHOCARDIOGRAM (06/03/08)(06/03/08)

Concentric left ventricular hypertrophy with hypokinetic anterior Concentric left ventricular hypertrophy with hypokinetic anterior interventricular septum, anterior and lateral left ventricle from mid to interventricular septum, anterior and lateral left ventricle from mid to apex. Left ventricular ejection fraction is reduced, 56% (Teicholz) / apex. Left ventricular ejection fraction is reduced, 56% (Teicholz) / 52 % (Simpson’s). Normal left atrial dimension. Normal right atrial 52 % (Simpson’s). Normal left atrial dimension. Normal right atrial and ventricular dimensions. Normal main pulmonary artery diameter. and ventricular dimensions. Normal main pulmonary artery diameter. Normal diameter of aortic root and proximal ascending aorta (2.5 Normal diameter of aortic root and proximal ascending aorta (2.5 cm). Thickened margins of right and non-coronary cusps of aortic cm). Thickened margins of right and non-coronary cusps of aortic valve leaflets with normal mobility pattern. Normal mitral, tricuspid valve leaflets with normal mobility pattern. Normal mitral, tricuspid and pulmonic valves.and pulmonic valves.

Color Flow and Doppler study:Color Flow and Doppler study: Mitral regurgitation, mild. Tricuspid Mitral regurgitation, mild. Tricuspid regurgitation, mild. Normal pulmonary artery pressure (by pulmonary regurgitation, mild. Normal pulmonary artery pressure (by pulmonary acceleration time >110 msec). Normal left ventricular diastolic acceleration time >110 msec). Normal left ventricular diastolic function indices (E/A ratio = 1.3; IVRT = 80 msec) function indices (E/A ratio = 1.3; IVRT = 80 msec)

CT ANGIOGRAPHYCT ANGIOGRAPHY

6/3/086/3/08 Bilateral marked pneumonic Bilateral marked pneumonic

consolidation in both lower lobes as consolidation in both lower lobes as well as in the upper lung regionswell as in the upper lung regions

Normal Ct angiography of the Normal Ct angiography of the pulmonary vessels including the pulmonary vessels including the thoracic aortathoracic aorta

No evident pulmonary embolismNo evident pulmonary embolism

ECG POST PTCAECG POST PTCA

2020H non-sustained v-tach2020H non-sustained v-tach Magnesium Sulfate 4 gram in 50ml D5w Magnesium Sulfate 4 gram in 50ml D5w

x 30minx 30min

Dopamine inotropic supportDopamine inotropic support

First Hospital DayFirst Hospital Day

Coffee ground/per Coffee ground/per NGT Enoxaparine NGT Enoxaparine discontinueddiscontinued

Repeat Cardiac EnRepeat Cardiac Enzymeszymes

Diagnostic TestDiagnostic Test HypercoagulableHypercoagulable

Work-up Work-up

MedicationsMedications Dopamine / Dopamine /

DobutamineDobutamine Furosemide 40mg Furosemide 40mg Piperacillin Piperacillin

TazobactamTazobactam MetoprololMetoprolol NicorandilNicorandil

ECG on 1ECG on 1stst HD HD

22ndnd HD HD Episodes of Episodes of

hypotensionhypotension

Bilateral Rales (base-Bilateral Rales (base-mid)mid)

CXR increased CXR increased congestioncongestion

Episodes of Chest Episodes of Chest PainPain

TreatmentTreatment Dopamine Dopamine

/Dobutamine/Dobutamine Furosemide Furosemide

IncreasedIncreased

NTG patch NTG patch transfer of patient transfer of patient

to ICU was done. to ICU was done.

33rdrd HD HDContinuous titration of Dopamine/ Dobutamine Continuous titration of Dopamine/ Dobutamine

Increased FurosemideIncreased Furosemide

Correction with KCLCorrection with KCL

Episodes of Episodes of HypotensionHypotension

Persistence of Persistence of pulmonary pulmonary congestioncongestion

Electrolyte Electrolyte abnormalitiesabnormalities

44thth HD HD

Repeat 2d Echo (6/7/08)Repeat 2d Echo (6/7/08) Concentric left ventricular hypertrophy Concentric left ventricular hypertrophy

with segmental wall motion abnormality with segmental wall motion abnormality over left anterior descending artery over left anterior descending artery distribution with preserved global distribution with preserved global systolic function, EF 59%systolic function, EF 59%

Dilated aortic root aortic sclerosis, MR Dilated aortic root aortic sclerosis, MR moderate, TR mildmoderate, TR mild

Improvement of thickening of anterior Improvement of thickening of anterior and lateral wall compared to (6/3/08)and lateral wall compared to (6/3/08)

66thth HD HD

Weaning Started via SIMVWeaning Started via SIMV IV amiodarone shifted to OralIV amiodarone shifted to Oral Tapering of Pressors StartedTapering of Pressors Started CXR showed clearing of pulmonary CXR showed clearing of pulmonary

congestioncongestion

77thth HD HD

Patient extubatedPatient extubated NGT removed NGT removed Clear liquid diet with 1.2L/dayClear liquid diet with 1.2L/day Tapering of Dobutamine StartedTapering of Dobutamine Started

On the 10On the 10thth HD HD

Normal CXRNormal CXR Dobutamine Dobutamine

tapered offtapered off Anti-Anti-CardiolipinCardiolipin

ResultsResults

Warfarin 5mg Warfarin 5mg initially initially

Warfarin 2.5mg Warfarin 2.5mg ODOD

On the 24On the 24thth HD HD Discharged Stable and ImprovedDischarged Stable and Improved Home MedicationsHome Medications

ASA 80 mg tablet 1 tablet dailyASA 80 mg tablet 1 tablet dailyClopidogrel 75 mg tablet 1 tablet dailyClopidogrel 75 mg tablet 1 tablet dailyNicorandil 10 mg tablet ½ tablet 2x a dayNicorandil 10 mg tablet ½ tablet 2x a dayAmiodarone 200 mg tablet 1 tablet 2x a dayAmiodarone 200 mg tablet 1 tablet 2x a dayCilostazol 100 mg tablet 1 tablet 2x a dayCilostazol 100 mg tablet 1 tablet 2x a dayMetoprolol 50 mg tablet ½ tablet 2x a dayMetoprolol 50 mg tablet ½ tablet 2x a dayAtorvastatin 40 mg tablet 1 tablet once a Atorvastatin 40 mg tablet 1 tablet once a

daydayWarfarin (Coumadin) 5 mg tablet T – ThWarfarin (Coumadin) 5 mg tablet T – Th

2.5 mg tablet M W F ST SU2.5 mg tablet M W F ST SU

DISCHARGE DISCHARGE DIAGNOSIS:DIAGNOSIS:

Myocardial Infarction Left Main Myocardial Infarction Left Main Segment KILLIP IIISegment KILLIP III

Pulmonary CongestionPulmonary Congestion S/P CVD Lacunar Infarct LMCA (May S/P CVD Lacunar Infarct LMCA (May

2008)2008) S/P PTCA (6/3/08)S/P PTCA (6/3/08) T/Connective Tissue DiseaseT/Connective Tissue Disease

Anti-phospholipid Antibody Syndrome Anti-phospholipid Antibody Syndrome SuspectSuspect

DISCUSSIONDISCUSSION

DEFINITIONDEFINITION

Myocardial infarction (MI) is the irreversible Myocardial infarction (MI) is the irreversible necrosis of heart muscle secondary to necrosis of heart muscle secondary to prolonged ischemia. prolonged ischemia. Detection of Detection of rise/fall of cardiac biomarkersrise/fall of cardiac biomarkers together with evidence of myocardial ischemiatogether with evidence of myocardial ischemia with with at least oneat least one Symptoms of ischemiaSymptoms of ischemia ECG changesECG changes Pathologic Q waves in ECGPathologic Q waves in ECG Evidence of loss of viable myocardium or Evidence of loss of viable myocardium or

wall motion wall motion

EpidemiologyEpidemiology

Myocardial infarction (MI) under the Myocardial infarction (MI) under the age of 40 years accounts for around age of 40 years accounts for around 3%-10% of cases of coronary artery 3%-10% of cases of coronary artery disease. disease.

Incidence of MI is approximately 8 Incidence of MI is approximately 8 times lower in patients 18 to 45 times lower in patients 18 to 45 years than in older patients years than in older patients

Clinical PresentationClinical Presentation

-Angina progressing rapidly to fully -Angina progressing rapidly to fully evolved myocardial infarctionevolved myocardial infarction

-Symptoms present less than 1 week -Symptoms present less than 1 week durationduration

-Rarely presents with classic -Rarely presents with classic presentation of worsening angina presentation of worsening angina culminating in MIculminating in MI

Causes of MI the YoungCauses of MI the Young

Causes of MI in the Causes of MI in the YoungYoung

Cocaine AbuseCocaine Abuse Atheromatous Coronary Artery DiseaseAtheromatous Coronary Artery Disease Coronary Artery Dissection/ AneurysmCoronary Artery Dissection/ Aneurysm

Kawasaki’s, TakayasusKawasaki’s, Takayasus Hypercoagulable Hypercoagulable StateState

Anti-phospolipid Antibody Syndrome Anti-phospolipid Antibody Syndrome (primary/secondary)(primary/secondary)

Factor V LeidenFactor V Leiden

Atheromatous Coronary Atheromatous Coronary Artery DiseaseArtery Disease

80% of acute myocardial infarction 80% of acute myocardial infarction in the youngin the young

The atheromatous process starts The atheromatous process starts earlyearly

CHD was found in 20% of men and CHD was found in 20% of men and 8% of women between the ages of 8% of women between the ages of 30 and 34 years of age30 and 34 years of age

Rom J Intern MedRom J Intern Med, January 2006 Ginghin et al, January 2006 Ginghin et al

Non-Atheromatous Non-Atheromatous Coronary Artery DiseaseCoronary Artery Disease

Aortic DissectionAortic Dissection Aneurysms, ectasia, and anomalous Aneurysms, ectasia, and anomalous

origin of coronary arteriesorigin of coronary arteries Coronary artery aneurysms Coronary artery aneurysms

congenital or acquired secondary to congenital or acquired secondary to KKawasaki’s disease in childhoodawasaki’s disease in childhood

MI with Normal Coronary MI with Normal Coronary ArteriesArteries

Coronary Artery Coronary Artery SpasmSpasm

Hypercoagulable Hypercoagulable StatesStates

Embolic Embolic PhenomenaPhenomena Embolic Embolic

phenomenaphenomena Paroxidical Paroxidical

PhenomenaPhenomena

1-12% occurence based on 1-12% occurence based on Coronary AngiographyCoronary Angiography

Typical patient is young, Typical patient is young, without any previous history of without any previous history of chest painchest pain

Mean age at largest series of Mean age at largest series of MI in patients with normal MI in patients with normal coronary arteries patients, was coronary arteries patients, was 43 years and 43% were women.43 years and 43% were women.

significantly less frequent significantly less frequent angina prior to myocardial angina prior to myocardial infarction. infarction.

cardiovascular risk profile is cardiovascular risk profile is lower than that of patients with lower than that of patients with CAD,CAD, Characteristics and Prognosis of Myocardial Infarction in Patients Characteristics and Prognosis of Myocardial Infarction in Patients

With Normal Coronary ArteriesWith Normal Coronary Arteriesfrom from CHESTPeter Ammann, MD; Sabine Marschall, MD; Martin Peter Ammann, MD; Sabine Marschall, MD; Martin Kraus, MD; Lucius Schmid, MD; Walter Angehrn, MD; Reto Kraus, MD; Lucius Schmid, MD; Walter Angehrn, MD; Reto Krapf, MD and Hans Rickli, MDKrapf, MD and Hans Rickli, MD

MI related to substance MI related to substance AbuseAbuse

Cocaine use is Cocaine use is associated with associated with various cardiac various cardiac complications complications including MI.including MI.

48% of non-traumatic 48% of non-traumatic chest pain in the chest pain in the young associated with young associated with cocaine usecocaine use

6% MI at ER. after 6% MI at ER. after various complications various complications after cocaine use.after cocaine use. Cardiovascular Complications of

Cocaine UseRichard A. Lange, M.D., and L. David

Hillis, M.D.

Hypercoagulable StatesHypercoagulable States

PRIMARYPRIMARY SECONDARYSECONDARYAntithrombin deficiencyAntithrombin deficiency

Antiphospholipid syndromeAntiphospholipid syndrome

Protein C deficiencyProtein C deficiency

Factor V LeidenFactor V Leiden

Disorders of the Disorders of the fibrinolytic system fibrinolytic system

HypoplasminogenemiaHypoplasminogenemia

Abnormal plasminogenAbnormal plasminogen

Plasminogen activator Plasminogen activator deficiencydeficiency

Factor XII deficiencyFactor XII deficiency

DysfibrinogenemiaDysfibrinogenemia

Others: elevation of factor Others: elevation of factor VIIIVIII

Abnormalities of coagulation and Abnormalities of coagulation and fibrinolysisfibrinolysis

Trosseau syndromeTrosseau syndrome

Nephrotic syndromeNephrotic syndrome

Abnormalities of the blood vessels Abnormalities of the blood vessels and flowand flow

Venous stasisVenous stasis

HomocystinuriaHomocystinuria

Thrombotic thrombocytopenic Thrombotic thrombocytopenic purpurapurpura

Abnormalities of the plateletsAbnormalities of the platelets

Myeloproliferative disordersMyeloproliferative disorders

Paroxysmal hemoglobinuriaParoxysmal hemoglobinuria

Diabetes mellitusDiabetes mellitus

Clotting CascadeClotting Cascade

Factor V Leiden (resistance to Factor V Leiden (resistance to APC)APC)

SiteSite Venous, occasional Venous, occasional arterial, arterial,

DxDx -APC resistance assay-APC resistance assay

aPTT with exogenous aPTT with exogenous APC / aPTT without APC / aPTT without APCAPC

Normal > 2.2Normal > 2.2

-modified APC--modified APC-resistance assay.resistance assay.

-FV leiden DNA--FV leiden DNA-based analysis by based analysis by PCR :PCR :

Loss of principal aPC Loss of principal aPC cleavage site on factor cleavage site on factor V protein→ Resistance V protein→ Resistance to inactivation of Factor to inactivation of Factor Va by APC Va by APC

Anti-phospholipid Antibody Anti-phospholipid Antibody SyndromeSyndrome

Autoimmune thrombotic disease.Autoimmune thrombotic disease. It is characterized by recurrent arterial It is characterized by recurrent arterial

or venous thrombosis, recurrent fetal or venous thrombosis, recurrent fetal loss or in-utero death and/or loss or in-utero death and/or thrombocytopeniathrombocytopenia

CVD most frequent thromboembolic CVD most frequent thromboembolic manifestationsmanifestations

MI with normal coronary arteriesMI with normal coronary arteries presence of AAS among young patients presence of AAS among young patients

with AMI ranges from 14% to 21%,with AMI ranges from 14% to 21%, Rev Clin Esp.  2001; 201(3):118-21 (ISSN: 0014-2565)Seijas M ; Martínez Vázquez C ; Rivera A ; Rayo N ; Ordi-Ros J ; Nodar A ; Picón J

DIAGNOSTIC CRITERIA FOR APASDIAGNOSTIC CRITERIA FOR APASInternational Consensus Statement on an update of International Consensus Statement on an update of

the classification criteria for definite Antiphospholipid Syndrome 2006.the classification criteria for definite Antiphospholipid Syndrome 2006.

Clinical CriteriaClinical Criteria Laboratory CriteriaLaboratory Criteria

• • Vascular thrombosis – one Vascular thrombosis – one or more episodes of arterial, or more episodes of arterial, venous or small vessel venous or small vessel thrombosis in any tissue or thrombosis in any tissue or organ.organ.

(confirmed by imaging, (confirmed by imaging, Doppler studies or Doppler studies or histopathology)histopathology)

• • Recurrent pregnancy loss.Recurrent pregnancy loss.

• • Anticardiolipin antibody of Anticardiolipin antibody of IgG and/or IgM isotype on IgG and/or IgM isotype on twotwo

occasions at least 12 weeks occasions at least 12 weeks apart.apart.

• • Lupus anticoagulant in Lupus anticoagulant in plasma on two occasions at plasma on two occasions at least 12 weeks apart.least 12 weeks apart.

* Anti b2 glycoprotein I * Anti b2 glycoprotein I Antibody of IgG or IgM Antibody of IgG or IgM isotype in serum or plasma isotype in serum or plasma present on two occasions at present on two occasions at least 12 weeks apartleast 12 weeks apart

ANTIPHOSPHOLIPID ANTIPHOSPHOLIPID ANTIBODY SYNDROMEANTIBODY SYNDROME

ALGORITHMIC APPROACH TO ALGORITHMIC APPROACH TO APASAPAS

Management of Acute Management of Acute Myocardial InfarctionMyocardial Infarction

Reperfusion (minimize total ischemic Reperfusion (minimize total ischemic time)time)

Restoration of balance between O2 Restoration of balance between O2 supply and demandsupply and demand

Pain Relief Pain Relief Prevention of CompilationsPrevention of Compilations

GOLDEN PERIODGOLDEN PERIOD

MEDICAL MEDICAL MANAGEMENTMANAGEMENT

ANALGESIA- MORPHINEANALGESIA- MORPHINE

ASPIRINASPIRIN

BETA BLOCKERSBETA BLOCKERS

ACE INHIBITORS/ ARBACE INHIBITORS/ ARB

THIENOPYRIDINESTHIENOPYRIDINES

REPERFUSIONREPERFUSION

Primary Invasive Primary Invasive StrategyStrategy Goal Door To Goal Door To

balloon time 90 balloon time 90 minutesminutes

May give >12 hoursMay give >12 hours Patients with Patients with

caridogenic shockcaridogenic shock Primary PTCAPrimary PTCA Facilitated PTCAFacilitated PTCA Rescue PTCARescue PTCA

Fibrinolytic Therapy Fibrinolytic Therapy Door to needle time Door to needle time

30minutes 30minutes May give within 12 May give within 12

hours of onset of hours of onset of symptomssymptoms

ContraindicationsContraindications HemorrhageHemorrhage Intracranial Intracranial

mass/strokemass/stroke AVMAVM Active bleedingActive bleeding

2007 Focused Update of the ACC/AHA

SECONDARY SECONDARY PREVENTIONPREVENTION

CONTROL OF MODIFIABLE RISK CONTROL OF MODIFIABLE RISK FACTORSFACTORS SMOKING CESSATIONSMOKING CESSATION WEIGHT LOSSWEIGHT LOSS EXERCISEEXERCISE LipidLipid and Sugar Management and Sugar Management

Anti-coagulation for Hypercoagulable Anti-coagulation for Hypercoagulable StatesStates

PROGNOSIS IN THE PROGNOSIS IN THE YOUNGYOUNG

Better outcomes during medium and Better outcomes during medium and short term follow-up due to better short term follow-up due to better baseline characteristics but may have baseline characteristics but may have higher long term morbidity and mortalityhigher long term morbidity and mortality

Greater influence of Modifiable Risk Greater influence of Modifiable Risk factors towards prognosisfactors towards prognosis

Increased prevalence of smoking, Increased prevalence of smoking, hypertension and obesity in the younghypertension and obesity in the young

Acute Myocardial Infarction in Young Adults from Acute Myocardial Infarction in Young Adults from American Heart American Heart JournalJournalElvis Brscic, MD, Elvis Brscic, MD, et alet al

MODIFIABLE RISK MODIFIABLE RISK FACTORSFACTORS

Observed that smoking, obesity, and Observed that smoking, obesity, and hypertension more prevalent in young, hypertension more prevalent in young, high-risk, post-MI patientshigh-risk, post-MI patients

dyslipidemia and diabetes were less dyslipidemia and diabetes were less prevalent.prevalent.

Smoking and hypertension were Smoking and hypertension were associated with a differentially increased associated with a differentially increased relative risk of adverse outcomes in relative risk of adverse outcomes in younger patients. younger patients.

need for aggressive efforts at minimizing need for aggressive efforts at minimizing modifiable risk factors in young patients modifiable risk factors in young patients at risk for and after MI.at risk for and after MI.

High-risk Myocardial Infarction in the Young: The VALsartan In Acute High-risk Myocardial Infarction in the Young: The VALsartan In Acute myocardial iNfarcTion (VALIANT) Trialmyocardial iNfarcTion (VALIANT) Trial

APAS TREATMENTAPAS TREATMENT1.1. PROPHYLAXISPROPHYLAXIS2.2. PREVENTION OF FURTHER THROMBOSES OF PREVENTION OF FURTHER THROMBOSES OF

LARGE VESSELSLARGE VESSELS

- Low dose Aspirin 80 mg tablet 1 tablet once a dayLow dose Aspirin 80 mg tablet 1 tablet once a day- Hydroxychoroquine (reported to decrease the titers of Hydroxychoroquine (reported to decrease the titers of

APLAS)APLAS)- According to American College of Chest Physicians According to American College of Chest Physicians

Low Molecular Weight Heparin followed by Oral Low Molecular Weight Heparin followed by Oral anticoagulants (Warfarin) to maintain INR of at least 2.5 anticoagulants (Warfarin) to maintain INR of at least 2.5 for 12 months or longerfor 12 months or longer

RECOMMENDATIONSRECOMMENDATIONS

REPEAT ANTI-Cardiolipin Anti-body REPEAT ANTI-Cardiolipin Anti-body testing after 12 weekstesting after 12 weeks

Continue Clopidogrel and ASA for at Continue Clopidogrel and ASA for at least 14 daysleast 14 days

Rheumatology Follow-upRheumatology Follow-up Ant-coagulationAnt-coagulation

Thank YouThank You

ECGECG on admission on admission

CXRCXR On admission On admission

Admission Admission

COMPLETE BLOOD COUNTCOMPLETE BLOOD COUNT

HBHB HCTHCT RBCRBC WBCWBC LYMPHLYMPH SEGSEG PLTPLT

17.017.0 47.947.9 6.06.0 17.1717.17 7070 2020 286,000286,000

NaNa KK CREATCREAT TROP ITROP I TCPKTCPK CPKMBCPKMB CBGCBG

140.0140.0 3.33.3 1.01.0 0.00.0 64.064.0 0.60.6 162.0162.0

PROTIME:PROTIME: 109.9% activity, 0.9 INR 109.9% activity, 0.9 INR

PTT:PTT: Patient 28.2 (25.1 – 33.9 sec) Patient 28.2 (25.1 – 33.9 sec)

Control 29.1 secondsControl 29.1 seconds

ABGABG POST INTUBATION POST INTUBATION

PO2PO2 60.360.3 HCO3HCO3 21.621.6

PHPH 7.467.46 02 SAT02 SAT 9292

PCO2PCO2 26.426.4 BEBE -3.6-3.6

FIO2FIO2 100100

PEEPPEEP

MODEMODE ACAC

DAY 2DAY 2NaNa KK BUNBUN CREATCREAT CPKMCPKM

BBMgMg

138.0138.0 3.53.5 21.021.0 1.21.2 1123.21123.2 1.91.9

HBHB HCTHCT RBCRBC WBCWBC SEGSEG LYMPLYMPHH

MONOMONO PLTSPLTS

15.1015.10 43.1043.10 5.425.42 22.2722.27 7878 1010 1212 221,00221,0000

URINALYSISURINALYSISCOLOR COLOR

YELLOWYELLOW

TRANSPARENCYTRANSPARENCY HAZYHAZY

PHPH 7.57.5

GRAVITYGRAVITY 1.011.01

PROTIENPROTIEN NEGATIVENEGATIVE

KETONESKETONES NEGATIVENEGATIVE

NITRITESNITRITES NEGATIVENEGATIVE

ESTERASEESTERASE NEGATIVENEGATIVE

BLOODBLOOD 33

RBCRBC 255255

EPITHELIALEPITHELIAL 11

RBCRBC 255255

WBCWBC 22

BACTERIABACTERIA 11

HYPERCOAGULABLE HYPERCOAGULABLE Work upWork up

ANTI-CARDIOLIPIN IgGANTI-CARDIOLIPIN IgG ANTI-CARDIOLIPIN IgMANTI-CARDIOLIPIN IgM

HOMOCYSTIENHOMOCYSTIENE E 12.512.5 (5-15)(5-15)

Protein Protein cc 4.594.59

(4.62-(4.62-4.94)4.94)

Protein Protein ss 1717

(13.5-(13.5-24.1)24.1)

Hypercoagulable Hypercoagulable Work-UpWork-Up

Functional assay Functional assay for antihrombin III, for antihrombin III, C , SC , S

Lupus Lupus anticoagulantanticoagulant

Plasma Plasma homocysteinehomocysteine

Antiphospholipid Antiphospholipid antibodiesantibodies

Clotting assay Clotting assay activated protein C activated protein C resistanceresistance

Factor V LeidenFactor V Leiden Prothrombin gene Prothrombin gene

mutationmutation

WORK-UPWORK-UP

Anti-Cardiolipin Ig GAnti-Cardiolipin Ig G 3 mpl(<15)3 mpl(<15)

Anti-Cardiolipin Ig Anti-Cardiolipin Ig MM

13mpl (<12.5)13mpl (<12.5)

6/16/086/16/08

ESRESR 4343

ANAANA NegativeNegative

CRPCRP negativenegative

Chest X-rayChest X-ray

6/3/08 normal6/3/08 normal 6/3/08 (post intubation) prominent 6/3/08 (post intubation) prominent

pulmonary vasculature with pulmonary pulmonary vasculature with pulmonary congestion E.T. 2 cm above the carinacongestion E.T. 2 cm above the carina

6/5/08 progression of pulmonary 6/5/08 progression of pulmonary congestion, still with pulmonary edemacongestion, still with pulmonary edema

6/9/08 complete clearing of pulmonary 6/9/08 complete clearing of pulmonary congestioncongestion

DiagnosticsDiagnostics

6/3/20086/3/2008 6/3/20086/3/2008 6/4/20086/4/2008 1250H1250H 1646H1646H D-dimerD-dimer 642.6642.6

CPKCPK 0.60.6 11001100 1123.21123.2

cpkmbcpkmb 6464 1862018620 98109810

trop Itrop I 00

ALGORITHMIC APPROACH TO ALGORITHMIC APPROACH TO APASAPAS

ECGECG

6/3/08 (1030H) ST Elevation 6/3/08 (1030H) ST Elevation Myocardial Infarction anterolateral Myocardial Infarction anterolateral wall elevationwall elevation

6/3/08( 1330H) Acute St Elevation 6/3/08( 1330H) Acute St Elevation Myocardial Infarction MIMyocardial Infarction MI

6/4/08 antero-septal wall myocardial 6/4/08 antero-septal wall myocardial infarction with reciprocal changes in infarction with reciprocal changes in the inferior leadsthe inferior leads

Cardiac disease in the antiphospholipid syndrome: recommendations for treatment. Committee Cardiac disease in the antiphospholipid syndrome: recommendations for treatment. Committee consensus report.consensus report.Lupus. 2003; 12(7):518-23 (ISSN: 0961-2033)Lupus. 2003; 12(7):518-23 (ISSN: 0961-2033)Lockshin M ; Tenedios F ; Petri M ; McCarty G ; Forastiero R ; Krilis S ; Tincani A ; Erkan D ; Lockshin M ; Tenedios F ; Petri M ; McCarty G ; Forastiero R ; Krilis S ; Tincani A ; Erkan D ; Khamashta MA ; Shoenfeld YKhamashta MA ; Shoenfeld YHospital for Special Surgery, Barbara Volcker Center for Women and Rheumatic Diseases, Hospital for Special Surgery, Barbara Volcker Center for Women and Rheumatic Diseases, New York, NY 10021, USA. LockshinM@hss.eduNew York, NY 10021, USA. LockshinM@hss.edu

RECOMMENDATIONS:RECOMMENDATIONS:Valve abnormalities: anticoagulation is recommended for symptomatic patients with valvulopathy. Valve abnormalities: anticoagulation is recommended for symptomatic patients with valvulopathy.

Prophylactic antiplatelet therapy may be appropriate for asymptomatic patients Prophylactic antiplatelet therapy may be appropriate for asymptomatic patients (recommended by 13/17 experts in an independent review).(recommended by 13/17 experts in an independent review).

Committee members disagreed whether corticosteroid therapy is helpful, but agree that Committee members disagreed whether corticosteroid therapy is helpful, but agree that distinguishing among presumptive valvulitis (valve thickening on echocardiogram), valve distinguishing among presumptive valvulitis (valve thickening on echocardiogram), valve deformity and vegetations is important, as treatment implications may differ. deformity and vegetations is important, as treatment implications may differ.

Occlusive arterial disease (angina, myocardial infarction): the Committee recommends Occlusive arterial disease (angina, myocardial infarction): the Committee recommends aggressive treatment of all risk factors for atherosclerosis (hypertension, aggressive treatment of all risk factors for atherosclerosis (hypertension, hypercholesterolaemia, smoking) and liberal use of folic acid, B vitamins and cholesterol-hypercholesterolaemia, smoking) and liberal use of folic acid, B vitamins and cholesterol-lowering drugs (preferably statins). lowering drugs (preferably statins).

Hydroxychloroquine for cardiac protection in APS patients may be considered. Hydroxychloroquine for cardiac protection in APS patients may be considered. The Committee also recommends warfarin anticoagulation for those who have suffered The Committee also recommends warfarin anticoagulation for those who have suffered

thrombosis in the absence of atherosclerosis, but recognizes that developing data may thrombosis in the absence of atherosclerosis, but recognizes that developing data may support the use of antiplatelet agents instead. Intracardiac thrombi:support the use of antiplatelet agents instead. Intracardiac thrombi:

the Committee recommends intensive warfarin anticoagulation, and consultation with cardiac the Committee recommends intensive warfarin anticoagulation, and consultation with cardiac surgeons when appropriate. Ventricular dysfunction: surgeons when appropriate. Ventricular dysfunction:

SummarySummary The objective of this study was to highlight the need for The objective of this study was to highlight the need for

investigation of antiphospholipid (aPL) antibodies in investigation of antiphospholipid (aPL) antibodies in patients presenting with myocardial infarction (MI) and patients presenting with myocardial infarction (MI) and normal coronary arteries at angiography. We present five normal coronary arteries at angiography. We present five patients who were found to have had an MI without patients who were found to have had an MI without evidence of atherosclerosis. All had aPL antibodies and evidence of atherosclerosis. All had aPL antibodies and thus fulfilled the diagnosis of antiphospholipid syndrome thus fulfilled the diagnosis of antiphospholipid syndrome (APS). Who did not have recurrent events on long-term (APS). Who did not have recurrent events on long-term anticoagulation maintaining an international normalised anticoagulation maintaining an international normalised ratio of 3–4. This study suggests that APS is probably a ratio of 3–4. This study suggests that APS is probably a major cause of MI in those with normal coronary arteries major cause of MI in those with normal coronary arteries at angiography. It is an important diagnosis to make as at angiography. It is an important diagnosis to make as they do not require anti-atherosclerotic treatment but they do not require anti-atherosclerotic treatment but appear, from this case series, to do well on high-dose appear, from this case series, to do well on high-dose warfarin. Further clinical studies are necessary to look at warfarin. Further clinical studies are necessary to look at prevalence and best management in these patients.prevalence and best management in these patients.

CtCt scan scan

6/3/086/3/08 Suggestive lacunar Suggestive lacunar

infarct in the left infarct in the left temporo-parietal temporo-parietal subcortical areasubcortical area

Unremarkable Ct Unremarkable Ct scan examination scan examination of the rest of the of the rest of the brainbrain

BETA-BLOCKERBETA-BLOCKER

Oral B-blockers should be given in the first 24 hoursOral B-blockers should be given in the first 24 hours

IV B-blockers may be given at time of presentationIV B-blockers may be given at time of presentation

ContraindicationsContraindications 1) signs of heart failure, 1) signs of heart failure, 2) evidence of2) evidence of a low output state, a low output state, 3) increased risk* for cardiogenic shock, 3) increased risk* for cardiogenic shock, 4) relative contraindications to beta blockade 4) relative contraindications to beta blockade

(Level of Evidence: B)(Level of Evidence: B)

2007 AHA STEMI (MODIFIED RECOMMENDATION)2007 AHA STEMI (MODIFIED RECOMMENDATION)CLASS ICLASS I

ClopidogrelClopidogrel

recommended to administer recommended to administer loading dosse of loading dosse of Clopidogrel 300mgClopidogrel 300mg

Clopidogrel 75 mg daily + ASAClopidogrel 75 mg daily + ASA in STEMI px in STEMI px regardless of whether they undergo regardless of whether they undergo reperfusion with fibrinolytic therapy (at least reperfusion with fibrinolytic therapy (at least 14 day14 day

Long term maintenance therapy with Long term maintenance therapy with clopidogrel 75mg daily is reasonable for clopidogrel 75mg daily is reasonable for STEMI patientSTEMI patient

Lipid ControlLipid Control

HDL >50 in females > 40 in malesHDL >50 in females > 40 in males LDL 100> in non diabetics, 70>in diabetics and LDL 100> in non diabetics, 70>in diabetics and

high risk patientshigh risk patients Increase Omega 3 intakeIncrease Omega 3 intake Promotion of daily physical activityPromotion of daily physical activity

High Serum Cholesteryl Ester Transfer Rates and Small High-Density High Serum Cholesteryl Ester Transfer Rates and Small High-Density Lipoproteins Are Associated With Young Age in Patients With Acute Lipoproteins Are Associated With Young Age in Patients With Acute Myocardial InfarctionMyocardial Infarction

KKaawasakiwasaki generalized vasculitis of unknown etiology generalized vasculitis of unknown etiology vasculitis is most severe in medium-sized arteries vasculitis is most severe in medium-sized arteries

but can also occur in veins, capillaries, small but can also occur in veins, capillaries, small arterioles, and larger arteries.arterioles, and larger arteries.

In severely affected vessels, the media develops In severely affected vessels, the media develops inflammation with necrosis of smooth muscle inflammation with necrosis of smooth muscle cells. leading to aneurysms. cells. leading to aneurysms.

Vessel wall becomes narrowed or occluded due Vessel wall becomes narrowed or occluded due to stenosis or a thrombus.to stenosis or a thrombus.

Cardiovascular death usually occurs from a MI Cardiovascular death usually occurs from a MI secondary to thrombosis of a coronary aneurysm secondary to thrombosis of a coronary aneurysm or from rupture of a large coronary aneurysmor from rupture of a large coronary aneurysm

Takayasu’s DiseaseTakayasu’s Disease chronic, progressive, chronic, progressive,

inflammatory, occlusive inflammatory, occlusive disease of the aorta and its disease of the aorta and its branches branches

Takayasu arteritis is Takayasu arteritis is heterogeneous. heterogeneous. MostMost patients present with patients present with systemic and vascular systemic and vascular symptoms; symptoms;

erythrocyte sedimentation erythrocyte sedimentation rate is elevated in most rate is elevated in most

Classification criteria (3 of 6 Classification criteria (3 of 6 criteria are necessary), acriteria are necessary), a

Age of 40 years or younger at Age of 40 years or younger at disease onsetdisease onset

Claudication of the Claudication of the extremitiesextremities

Decreased pulsation of one or Decreased pulsation of one or both brachial arteriesboth brachial arteries

Difference of at least 10 mm Difference of at least 10 mm Hg in systolic blood pressure Hg in systolic blood pressure between armsbetween arms

Bruit over one or both Bruit over one or both subclavian arteries or the subclavian arteries or the abdominal aortaabdominal aorta

Arteriographic narrowing or Arteriographic narrowing or occlusion of the entire aorta, occlusion of the entire aorta, its primary branches, or large its primary branches, or large arteries in the upper or lower arteries in the upper or lower extremitiesextremities

6/3/086/3/08

1125.1125.99

6/4/086/4/08

1073.1073.55

6/5/086/5/08

-253-2536/6/086/6/08

-350-3506/7/086/7/08

-390-3906/8/096/8/09

-150-150

40mg 40mg q12q12

40mg 40mg q 12q 12

40mg 40mg q 6q 6

40mg 40mg q 6q 6

40mg 40mg q 6q 6

40mg/40mg/odod

Figure 1. The Clotting Cascade. Coagulation is initiated by the exposure of blood to tissue factor bound to cell membranes. Tissue factor interacts with factor VIIa to convert factor IX to factor IXa and factor X to factor Xa (only the activated forms are shown). Factor IXa converts factor X to factor Xa. Factor Xa generates factor IIa (thrombin) from factor II (prothrombin). Each of these reactions takes place on an activated cell surface. Once factor IIa is generated, it cleaves plasma fibrinogen to generate fibrin. The tissue-factor-pathway inhibitor forms a quaternary structure with tissue factor, factor VIIa, and factor Xa (shown in blue). The thrombomodulin–protein C–protein S pathway (shown in yellow) inactivates factors Va and VIIIa. Antithrombin III inactivates factors XIa, IXa, Xa, and IIa (shown in orange) in a reaction that is accelerated by the presence of heparan sulfate. In the fibrinolytic pathway, tissue- type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) convert plasminogen to plasmin. Once generated, plasmin proteolytically degrades fibrin (