Emergency Cardiology

Holistic in Risk factors and Cardiovascular Management Warong Lapanun MD. Cardiology division Bhumibol Adulyadej Hospital Emergency Medicine Lunch Symposium: 2/9/07

Atherosclerosis

Cross-section through the wall of a healthy artery with intact endothelium, intima and smooth muscle bundles (SEM)

Artery demonstrating endothelial erosion (SEM)

Intimal thickening Extralipid pool Fibrous scar

Atheromatous plaque

Plaque Rupture

Coronary occlusion Plaque rupture Occlusive thrombus

Most Myocardial Infarctions Are Caused by Low-Grade Stenoses

Pooled data from 4 studies: Ambrose et al, 1988; Little et al, 1988; Nobuyoshi et al, 1991; and Giroud et al, 1992. (Adapted from Falk et al.)

Falk E et al, Circulation , 1995.

Features of a Ruptured Atherosclerotic Plaque

Eccentric, lipid-rich

Fragile fibrous cap

Prior luminal obstruction < 50%

Visible rupture and thrombus

Constantinides P. Am J Cardiol. 1990;66:37G-40G.

Plaque rupture triggers

Emotional stress

Physical activity

Vasospasm

Cathecholamines

Vulnerable Versus Stable Atherosclerotic Plaques Libby P. Circulation. 1995;91:2844-2850. Vulnerable Plaque

Thin fibrous cap

Inflammatory cell infiltrates:

proteolytic activity

Lipid-rich plaque

Lumen Lipid Core Fibrous Cap

Thick fibrous cap

Smooth muscle cells: more extracellular matrix

Lipid-poor plaque

Stable Plaque Lumen Lipid Core Fibrous Cap

Coronary Remodeling (Adapted from Glagov et al.) Normal vessel Minimal CAD Progression Compensatory expansion maintains constant lumen Expansion overcome: lumen narrows Severe CAD Moderate CAD Glagov et al, N Engl J Med , 1987.

Atherosclerosis: A Progressive Process Disease progression PHASE I: Initiation PHASE II: Progression PHASE III: Complication Normal Fatty Streak Fibrous Plaque Occlusive Atherosclerotic Plaque Plaque Rupture/ Fissure & Thrombosis MI Stroke Critical Leg Ischemia Coronary Death Unstable Angina Libby P. Circulation. 2001;104:365-372.

IVUS=intravascular ultrasound Nissen S, Yock P. Circulation 2001 ; 103: 604–616 Angiogram IVUS Little evidence of disease Atheroma No evidence of disease The IVUS technique can detect angiographically ‘silent’ atheroma

Correlation of CT angiography of the coronary arteries with intravascular ultrasound illustrates the ability of MDCT to demonstrate calcified and non-calcified coronary plaques (Becker et al., Eur J Radiol 2000) Non-calcified, soft, lipid-rich plaque in left anterior descending artery (arrow) . The plaque was confirmed by intravascular ultrasound (Kopp et al., Radiology 2004)

Estimated 10-Year CHD Risk in 55-Year-Old Adults According to Levels of Various Risk Factors : Framingham Heart Study A B C D Blood Pressure (mm Hg) 120/80 140/90 140/90 140/90 Total Cholesterol (mg/dL) 200 240 240 240 HDL Cholesterol (mg/dL) 50 50 40 40 Diabetes No No Yes Yes Cigarettes No No No Yes Source: Circulation 1998;97:1837-1847.

CHD Mortality 0 2 4 6 8 10 12 0 5 10 15 20 RR (95% CI), 3.77 (1.74-8.17) Follow-up, Y Cumulative Hazard (%) Yes No 866 288 852 279 834 234 292 100 The Kuopio Ischaemic Heart Disease Risk Factor Study Unadjusted Kaplan-Meier Curve No. at Risk Metabolic Syndrome Yes Metabolic Syndrome: 0 2 4 6 8 10 12 0 5 10 15 20 RR (95% CI), 2.43 (1.64-3.61) Follow-up, Y 866 288 852 279 834 234 292 100 CVD Mortality All Cause Mortality Lakka H-M, et al. JAMA . 2002;288:2709-2716. No 0 2 4 6 8 10 12 0 5 10 15 20 RR (95% CI), 3.55 (1.96-6.43) Follow-up, Y 866 288 852 279 834 234 292 100

The INTERHEART Study Metabolic risk factors and their influence on the occurrence of AMI

Feb. 1999 to Mar 2003, 15,000 cases of AMI were compared with 15,000 controls in 52 countries

The prevalence of modifiable RF, calculation of the population attributable risk (PAR)

Frequency of RF in total pop. – Frequency of RF in those without MI

Frequency of RF in total pop.

Yusuf S et al. Lancet 2004, 364;937-962

The INTERHEART Study Population Attributable Risk (cumulated men& women)

Smoking DM Abdo Obesity Abn Lipids

PAR in%

Western Europe 29.3 15.0 63.4 44.6

Central Eastern Eu 30.2 9.1 28.0 35.0

Middle East 45.5 15.5 25.9 70.5

Africa 38.9 16.7 58.4 74.1

South Asia 37.4 11.8 37.7 58.7

South East Asia+ Japan 36.7 21.0 58.0 67.7

Australia+NZ 44.8 7.2 61.3 43.4

South America 38.3 17.7 45.5 47.6

North America 26.1 13.0 59.5 50.5

All 52 countries 36.4 12.3 33.7 64.1

INTERHEART: Risk of AMI Associated With Risk Factors

Risk Factor Control(%) Case AMI(%) OR ( adj.for age,sex, smoking)

Lipid(ApoB/ApoA-1) 20.0 33.5 3.87

Current smoking 26.8 45.2 2.95

DM 7.5 18.4 3.08

HT 21.9 39.0 2.48

Abdo. Obesity 33.3 46.3 2.22

Psychosocial 2.51

Veg.& Fruit daily 42.4 35.8 0.70

Exercise 19.3 14.3 0.72

Alcohol intake 24.5 24.0 0.79

Discharge Dx

Gender

Risk factors

Prevalence of RF according to gender

Relationship Between Changes in LDL-C and HDL-C Levels and CHD Risk Third Report of the NCEP Expert Panel. NIH Publication No. 01-3670 2001. http://hin.nhlbi.nih.gov/ncep_slds/menu.htm 1% decrease in LDL-C reduces CHD risk by 1% 1% increase in HDL-C reduces CHD risk by 3%

CHD Outcomes in Clinical Trials of LDL Cholesterol-Lowering Therapy Mean CHD CHD No. No. Person- cholesterol Incidence Mortality Intervention trials treated years reduction (%) (% change) (% change) Surgery 1 421 4,084 22 -43 -30 Sequestrants 3 1,992 14,491 9 -21 -32 Diet 6 1,200 6,356 11 -24 -21 Statins 12 17,405 89,123 20 -30 -29 Source: This table is adapted from the meta-analysis of Gordon, 2000.

Relation Between LDL-Cholesterol Reduction And Risk Of Cardiovascular Events % LDL-C Reduction 10 0 20 40 70 % Reduction In Risk Of Nonfatal MI Or CHD Pravastatin LRC-CPPT WOSCOPS CARE POSCH 4S (Simvastatin) 13 26 35 60 % LDL-C Reduction 10 0 20 40 70 % Reduction In Risk Of Nonfatal MI Or CHD (4.5 y) LRC-CPPT ( P >.05) WOSCOPS CARE POSCH ( P >.05) 4S (Simvastatin) 13 26 35 60 *

When outcomes at 4.5 y are considered, beneficial effects of statins occurred more rapidly

These effects may not be entirely cholesterol dependent; *difference possibly due to pleiotropic effects

Reproduced from Liao and Laufs. Annu Rev Pharmacol Toxicol . 2005;45:89, with permission from Annual Reviews . www.annualreviews.org. Liao. Am J Cardiol . 2005;96(suppl):24F.

Vessel Wall And Endothelial Cell Membrane Changes With Atherogenesis Reproduced from Mason et al. Circulation . 2004;109(suppl II):II-34, with permission. Mason et al. Am J Cardiol . 2005;96(suppl):11F.

Role Of Statins In ACS: Non-Lipid Effects ( Pleiotropic effects) ADP = adenosine diphosphate; CD40-L = CD40 ligand; IFN = interferon; IL = interleukin; vWF = von Willebrand factor. Reproduced from Ray and Cannon. J Thromb Thrombolysis . 2004;18:89, with permission. Cannon and Ray. Am J Cardiol . 2005;96:54F.

Clinical Events Correlate Directly With On-Treatment LDL-Cholesterol Levels P = placebo; S = statin. Reproduced from O'Keefe et al. J Am Coll Cardiol . 2004;43:2142, with permission. CHD Events (%) 10 9 8 7 6 5 4 3 2 1 0 -1 55 75 95 115 135 155 175 195 LDL Cholesterol (mg/dL) y = 0.0599x - 3.3952 R 2 = 0.9305 P =.0019 AFCAPS-S WOSCOPS-S ASCOT-S ASCOT-P AFCAPS-P WOSCOPS-P Primary prevention: 4-5 yr duration

ASCOT-LLA: Nonfatal MI And Fatal CAD Primary End Point Adapted from Sever et al. Lancet . 2003;361:1149, with permission. Sever et al. Am J Cardiol . 2005;96(suppl):39F. 2 0 1 4 3 Years 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Cumulative Incidence (%) Placebo Atorvastatin 10 mg Number of Events 36% Reduction HR = 0.64 (0.50-0.83) P =.0005 Number of Events 154 100 N=10,305

Effects of Lipid-Lowering Therapy on CHD Events in Statin Trials 25 20 15 10 5 0 Patients with CHD event (%) 90 110 130 150 170 190 210 S = statin-treated P = placebo-treated *Extrapolated to 5 y 4S - P CARE - P LIPID - P 4S - S WOSCOPS - S WOSCOPS - P AFCAPS - P AFCAPS - S LIPID - S CARE - S Primary prevention Simvastatin Pravastatin Lovastatin Modified from Kastelein JJP. Atherosclerosis. 1999;143(suppl 1): S17-S21. HPS - S HPS - P Atorvastatin ASCOT - S * ASCOT - P * Secondary prevention LDL-C (mg/dL)

PROVE IT-TIMI 22: A Major Cardiovascular Event Or Death From Any Cause Primary End Point Adapted from Cannon et al. N Engl J Med . 2004;350:1495, with permission. Ray and Cannon. Am J Cardiol . 2005;96(suppl):54F. 15 0 10 30 25 5 20 Months Of Follow-Up 0 3 9 15 21 6 12 18 24 27 30 Death Or Major Cardiovascular Event (%) Pravastatin 40 mg Atorvastatin 80 mg P =.005 Overall P =.03 n= 4,162 with CHD

PROVE IT-TIMI 22: Effect Of Different Statin Regimens On LDL Cholesterol And CRP

Biological Statin Response Regimen Baseline 30 Days 4 Months

LDL mg/dL (mean) Pravastatin 40 mg 106 88 97 Atorvastatin 80 mg 106 60 67 P value NS <.001 <.001 CRP mg/L (median) Pravastatin 40 mg 11.9 2.3 2.1 Atorvastatin 80 mg 12.2 1.6 1.3 P value NS <.001 <.001 Cannon et al. N Engl J Med . 2004;350:1495. Ridker et al. N Engl J Med . 2005;352:20. Reproduced from Ray and Cannon. Am J Cardiol . 2005;96(suppl):54F, with permission.

PROVE IT-TIMI 22: A Major Cardiovascular Event Or Death From Any Cause At Different Censoring Times Reproduced from Cannon et al. N Engl J Med . 2004;350:1495, with permission. Ray and Cannon. Am J Cardiol . 2005;96(suppl):54F. Censoring Time Hazard Ratio (95% CI) Risk Reduction (%) Event Rate (%) Atorvastatin Pravastatin 30 days 90 days 180 days End of follow-up 17 1.9 2.2 18 6.3 7.7 14 12.2 14.1 16 22.4 26.3 0.50 0.75 1.0 High-Dose Atorvastatin Better Standard-Dose Pravastatin Better 1.50 1.25

NCEP-ATP III National Cholesterol Education Program Adult Treatment Panel III

Evolution of Lipid Management Guidelines ATP I (1988) ATP II (1993) ATP III (2001) Diet; low-dose, nonstatin monotherapy High-dose statin, combination therapy Low- to moderate-dose statin monotherapy Increasing aggressiveness of cholesterol-lowering therapy The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP)

Update to ATP III: Risk Categories, LDL-C Goals Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines: Circulation . 2004;110:227-239. <160 <130 <130 <100 (optional <70) LDL-C Goal (mg/dL) > 160 > 130 > 130 > 100 Initial TLC (mg/dl) > 130 (optional 100-129) Moderately high risk: 2+ risk factors (10-year risk 10-20%) > 190 (optional 160-189) Lower risk: 0–1 risk factor >160 Moderate risk: 2+ risk factors (10-year risk  10%) > 100 (optional <100) High risk: CHD or CHD risk equivalents (10-year risk >20%) Consider drug (mg/dl) Risk Category

Am J Cardiol. 2004;93: 154-8

HDL LDL TG Total chol

Cardiac Emergency

Acute coronary syndrome

Arrhythmia

Hypertensive emergency

Aortic dissection

Cardiac tamponade

P : P recipitating , Position

Q : Quality and Quantity

R : Region, Radiate, Refer

S : Symptom associated

T : Timing , Terminating

Taking Hx of obscure pain

Acute myocardial infarction

Acute aortic dissection

Acute pulmonary embolism

Tension pneumothorax

Killer chest pain

Characteristics of Typical and Atypical angina pectoris (1)

Typical

Substernal

Burning, heavy, or squeezing feeling

Precipitated by exertion or emotion

Promptly relieved by rest of NTG

Angina chest pain

DDx of AMI

Aortic dissection

Acute pericarditis

Acute pulmonary embolism

Intercostal neuralgia

Costochondritis

Abdominal visceral disorders

PU, Pancreatitis, biliary colic

Atypical symptoms

Elderly

Women

Diabetes

Post operation

Angina equivalent

AMI Definition • Chest pain • ECG • Troponin positive

STEMI Blood flow Chest discomfort PMVT, VF Sudden Death M. Ischemia Heart failure Cardiogenic shock Elevated +CK,Trop-T M.stunning Consequences after acute coronary artery occlusion NSTEMI ,UA Cardiovascular Research & Prevention Center, Bhumibol Adulyadej hospital

Wave Front Theory LAD occlusion

False +ve Troponin

Cardioversion

Pulmonary embolism

Tachycardia

Decompensated heart failure

Sepsis

TIMI Risk Score for STEMI ( Total points 0-14 )

Historical Points

Age > 75 3

65-74 2

DM or HT or 1

Angina

Exam.

SBP<100 3

HR >100 2

Killip II-IV 2

Wt< 67kg( 150 lb) 1

Presentation

Ant. STE or LBBB 1

Time to Rx > 4 hr 1

Risk Score 30-d MR(%) 0 0.8 1 1.6 2 2.2 3 4.4 4 7.3 5 12 6 16 7 23 8 27 >8 36 Morrow et al. Circulaion 2000

Acute antero-lateral MI

Time From Onset of Symptoms Select a reperfusion strategy <12 hours >12 hours

How is “onset of symptoms”define d ?

Why the division between <12 and > 12 hours?

Select a Reperfusion Strategy

Thrombolytic Rx selected:

( no contraindication)

Front-loaded alteplase or

Streptokinase or

Reteplase

Goal: Door-to-drug<30 min

Primary PTCA selected: Goal

Door-to- Balloon < 90 min

Contraindication to thrombolyticRX Or Eqivalent alternative

Extensive antero-lateral ischemia

Effect of thrombolytic on mortality according to admission ECG Live save per thousand FTT Collaborative group: Lancet 1994; 343

Applicability and Efficacy of Lysis vs PCI 0% 50% 100% 100% 50% 0% Fribrinolysis Primary angioplsty Availability Availability 10% <50% Treated > 90% TIMI 3 > 90% Treated Reocclusion Stroke 54% TIMI 3 5% 0.1% 10% Reocclusion 1% Stroke 25% Reocclusion

Total ischemic time A B C ER Rx <30min (lytic) <90 min (PCI) CP reperfuse microvascular epicardial

การคัดกรอง

Fast Track MI

EKG ด่วนแพทย์ดูใน 10 นาที

 ST elevation ตาม staff cardio ทันที

No ST elevation ………………. MD.

30-day mortality (%) Relationship between 30-day mortality and Door to Balloon time( N=522 ) Berger et al. Circulation 1999;100:14-20 P=0.001

PCI vs Fibrinolysis with fibrin-specific agents

Fribrinolysis is generally preferred if

Early presentation < 3 hr from symptom onset and delay to invasive strategy

Invasive strategy is not an option

Cath-lab occupied/not available

Vascular access difficulties

Lack of access to a skilled PCI lab

Delay to invasive strategy

Prolonged transport

(D-to-B) - (D-to-N) > 1 hr

Contact-to-B or D-to-B > 90 min

Invasive Strategy is generally preferred if

Skilled PCI lab available with surgical backup

(D-to-B) - (D-to-N) < 1 hr

Contact-to-B or D-to-B < 90 min

Contraindications to fribrinolysis including increased risk of bleeding of ICH

Late presentation

The symptom onset was >3 hr ago

Assessment of Reperfusion Option for Patients with STEMI

Step 1: Assess Time and Risk

Time since onset of symptoms

Risk of STEMI

Risk of fibrinolysis

Time required for transport to a skilled PCI lab

Step 2 : Determine of Fibrinolysis or an Invasive Strategy is preferred

If presentation in < 3 hr and there is no delay to an invasive strategy, there is no preference for either strategy

Absolute Contraindication for thrombolytic Rx

A: Aortic dissection

B: Bleeding ( active in 2-4 wk or bleeding diathesis)

C: Cranial :

Any prior ICH,

3 mo of ischemic stroke or closed head trauma,

Intracranial neoplasm

D: Drug allergy

60 yo man, smoker, 1hr severe CP, BP 100/60

58 yo lady, DM HT, syncope, sweating, CP 2/10, BP 80/60

V4R

68 yo man, 3 hrs 8/10 CP, BP 100/60

Algorithm for ECG identification of the IRA in Anterior MI STE in V 1 , V 2 and V 3 STE in V1 (>2.5 mm) and AVL or RBBB with Q wave or both ST depression (<1 mm) in II, III, and AVF STE in II, III, and AVF Wrap around

A 63 yo lady, 3 hrs 7/10 CP Given Metalalyse + Clexane , continuing chest pain, VF x II in cath lab

AMI in LBBB

Q wave : not be used

Indicator : Primary ST change

ST deviation in the same( concordant) direction as the major QRS vector

Concordant ST changes

elevation > 1 mm concordant with QRS

ST depression > 1 mm in leads V1, V2, or V3

Extremely discordant

ST elevation > 5 mm discordant with QRS

ST elevation without infarction

LVH

LBBB

Benign early repolarization

Brugada’s syndrome

LV aneurysm

Acute pericarditis

Myocarditis

Ventricular pace rhythm

ED :55 yo man, 3 hrs Lt. CP 5/10, less with sits forward

GP: 34 yo athlete, anterior CP 3/10, pt. of tenderness Fish hook

60-yo man severe headache and collapsed

Conditions Associated with TDP

E’lyte abnormality

K + , Mg ++ , Ca ++

Drug-related

Antiarrhythmic

IA, IC, III

Psychotropic agents

Organophosphate

Liquid protein diet

Cardiac disease

IHD, myocarditis

Bradycardia

CNS disease

Intracranial lesion

SAH

Congenital LQTS

Tachycardia with pulse

Stable or unstable

Unstable ( rate usually >150/min)

Altered mental status

Chest pain

Hypotension

Signs of shock

If Unstable  Cardioversion

Cardioversion

AF : 100,200,300,360 J

Stable MMVT:100,200,300,360 J

SVT or A flutter:50,100,200,300,360 J

PMVT: Rx as VF

Synchronized mode?

Stable tachycardia Narrow QRS

SVT

Vagal ma.

Adenosine

6/12/12 mg IV

Regular Irregular Regular Irregular Wide QRS

AF, Aflutter, MAT: Diltriazem, B-blocker

MMVT

Amiodarone 150 mg iv in 10 min repeat as needed

Cardioversion

AF with WPW : Amiodarone 150 mg iv

TDP: MgSO 4 1-2 g iv

Treat possible contributing factors: 6H-5T

SVT after Rx with Adenosine 6mg IV

AF with WPW: How to Rx? Unstable : Cardioversion 100 J Stable : Amiodarone 150 mg IV

34-yo lady, gen. edema 3 mo.

Cardiac tamponade

Pericardiocentesis

Hemopericardium

23-y-old man with fever 7 day and chest pain

Pericardial fluid

Hypertensive crisis

Definition

Severe elevation in BP ( >220/120 mmHg)

Sub classified into emergency and urgency

Hypertensive emergency

Require an immediate reduction in BP ( 1 hr )

Rx IV therapy and in ICU

Hypertensive urgency

No evidence of progressive end-organ injury

Require only gradual reduction in BP in 24-48 hr

Wong, T. Y. et al. N Engl J Med 2004;351:2310-2317 Examples of Mild Hypertensive Retinopathy AV nicking Focal narrowing AV nicking Copper wiring

Accelerated-malignant HT

Fundoscopic changes

Retinal hemorrhages

Exudates

Papilledema

HT and autoregulation of CBF

CBF : cerebral perfusion pressure ( CPP)

CPP= MAP - ICP

MAP = DBP + 1/3 Pulse pressure

Cerebral Autoregulation Mean arterial pressure (mmHg) Cerebral blood flow (ml/100 gm per min ) 50 100 150 200 150 100 50 0 Normotensive Hypertensive Strandgaard S,et al; Br Med J 1:507, 1973

Goal of Rx in HT emergency

Reduce mean arterial BP no > 25%

Within minutes to 1 hours

Toward 160/110 mmHg within 2- 6 hours Toward normal BP in 24- 48 hours JNC VII. JAMA 2003;289:2560-2572

Pitfalls in the Rx

Excessive falls in BP should be avoided

ischemia : Renal, cerebral, cardiac

SL/ short acting Nifedipine: not recommended

Three exceptions

Ischemic stroke

Aortic dissection  SBP should < 100 mmHg (+/-)

Lower BP for thrombolytic Rx ( Stroke )

Acute ischemic stroke and BP

SBP>220 mmHg or DBP 120-140 mmHg

Caution reduction of BP 10%-15%

Carefully monitoring Neuro signs /BP

DBP> 140 mmHg

IV infusion of Na nitroprusside

Reduce BP 10%-15%

Lytic Rx within first 3 hrs

>185/110 mmHg : contraindication

BP > 180/105 mmHg : iv anti HT

American Stroke Association. Stroke 2003;34

Acute aortic dissection

Suspected diagnosis

 BP to the lowest tolerate level in 15-30 min

Initial Rx : IV NaNTP and IV Beta-blocker

Contraindication : hydralazine, nifedipine

Stimulation of sympathetic activity

Increase shear stress on the aortic wall

Approach to HT crisis BP > 220/120 mmHg Headache No neurosign No target organ damage Urgency Identify the cause and Rx the cause ( panic, anxiety) Otherwise use oral anti HTagent Neurosign( encep., stroke) Retinopathy gr III, IV severe chest pain ( IHD, dissecting aneu) Pulmonary edema Cathecholamine excess ARF Emergency IV therapy Recheck in 6-24 hr

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