DONE BY : Rasha Rakan Sara Al-zoubi · the tongue and rarely teeth pain and elbow ... Sweating and nausea are very dangerous sign. ... (Virchow's triad) •Platelets adhere, ...

DONE BY : Rasha Rakan Sara Al-zoubi

Ischemic heart disease

Introduction Ischemic heart disease: Oxygen isn’t reaching to the heart muscle

• In > 90% of cases: the cause is: reduced coronary blood flow secondary to: obstructive atherosclerotic vascular disease

…so most of the time it is called: coronary artery disease

• Decades for the clinical syndromes to develop (may be since childhood) chronic

• Causes other than coronary ischemia oxygen and nutrients aren’t reaching heart: other 10% of cases

- demand (e.g., heart rate or HTN)

- Shock blood sudden hemorrhage

- Anemia

- Pneumonia ( oxygenation)

- …etc. ( CO2 poising )

Pathogenesis

…can affect any of the coronary arteries

-left anterior descending (LAD)

-left circumflex (LCX)

-right coronary artery (RCA)

…singly or in any combination They are the most common but other small coronary artery can be affected

…clinically significant plaques can be located anywhere

…but tend to occur within the first several centimeters of the LAD

and LCX, and along the entire length of the RCA

Pathogenesis, cont’d • Fixed narrowing <70%: usually asymptomatic

• Fixed narrowing >70% = critical stenosis Symptoms starts to appear, and they will have stable angina Angina: Chest pain ( الذبحة الصدرة) When the patient feels angina, he rests and may put a pill of Nitric glycerin under his tongue (حبة تحت اللسان). Less than 10 minutes he will be fine.

• Fixed narrowing >90%...usually unstable angina (in the form of pain at rest)

• Thrombosis associated with a disrupted plaque often triggers the acute coronary syndromes (could be on of those unstable angina-MI-SCD sudden cardiac death)

Atherosclerosis stable fixed 70% stable angina Plaque rapture thrombus closed lumen acute coronary syndrome Cardiac cells are still alive

• Remember collateral perfusion very useful if it is formed. When there’s chronic light changes along the years, connections form between the epicardia arteries ( they are present but open if there was a non-life-threatening blockage, and they replace the blocked blood supply)

Chest pain will appear in stable angina, unstable angina and MI which we will differentiate in the following slides, but now we will discuss the characteristics of cardiac pain Typical characteristics of cardiac pain: 1.Central retrosternal ( in the middle of the chest posterior to the sternum) 2.Crushing or squeezing or heaviness ( تكثر مقولة حاس ف ثقل على صدري ) 3.Referring pain radiating to the left that tells us that its cause is cardiac pain: in the neck, the arm (upper, left), the jaw (left), the tongue and rarely teeth pain and elbow (but that is very rare). The reason is embryological, they were originated from the same heart origin It doesn’t increase with respiration. The pain we feel while respiration particularly at the end of inhalation is pleural and pericardial, viral caused irritation in one of them, and at inspiration they rub against each other. There’s no heart muscle involvement. When the patient points his finger on his chest and tells you that there is نغزة, it’s not cardiac pain. If the pain lasted more than 2 days, it’s not cardiac pain, because the patient won’t stay alive for 2 days if he had cardiac pain. Cardiac pain is caused by a problem that would kill the patient in matters of minutes. It’s not too short neither, matter of seconds. Sweating and nausea are common companions of chest pain, because of the sever stimulation of sympathetic system. Sweating and nausea are very dangerous sign. In diabetics and elderly, can have silent MI, which means they won’t develop symptoms, because the have a problem in autonomic innervation. But they may come with epigastric pain ( المعدةراس ) , we should do ECG.

Stable angina becomes unstable if: 1.the pain that used to happen only after an effort starts to happen at rest. 2.the pain that used to stop after resting and pills aren’t working. Regarding collateral perfusion, it makes the chances of elderly who develop IHD to survive more than younger people.

Pathogenesis, cont’d even partial luminal occlusion by thrombus can compromise blood flow, sufficiently to cause a small infarction of the innermost zone of the myocardium (subendocardial infarct) after plaque rapture the thrombus isn’t big enough to cause mural MI

MI part that is closer to the endocardium is more sensitive than the part that is closer to the epicardium, because the vessels that are involved are epicardial vessels so the further the layer the more effected it gets. Sub endocardial is better than acute coronary syndrome, but it may develop into it.

• Thrombosis as a process in atherosclerosis (other than that which is associated with rupture and sudden thrombosis) is associated with repair (organization and recanalization) chronic thrombosis during atherosclerosis accompany the inflammation in it , so the repair happens inside it (granulation tissue, angiogenesis) and plaque enlargement

• Thrombosis may cause small emboli in intramyocardial branches with small microinfarcts small sized

• Vasoconstriction is also important MI happens more from 6am to 12 pm because adrenergic stimulation is more there are naturally secreted mediators, but those vessels are abnormal. it increases narrowing and increases rupture risk because of spasms it applies pressure on the plaque

can be stimulated by:

(1) circulating adrenergic agonists drugs, or natural secretions from the body at certain periods of the day

(2) locally released platelet (come during atherosclerosis) contents it results in vasoconstriction

(3) imbalance between endothelial cell-relaxing factors (e.g., nitric oxide) and -contracting factors (e.g., endothelin) due to endothelial dysfunction so these vessels have more risk to have spasms and constriction.

(4) mediators released from perivascular inflammatory cells it results in vasoconstriction

Pathogenesis, acute Plaque Change

• In most patients, unstable angina, infarction, and sudden cardiac death occur because of abrupt plaque change followed by thrombosis—hence the term acute coronary syndrome

*acute coronary syndrome (MI / Unstable angina(chest pain at rest) /Sudden death)

Main cause : Acute thrombus on a ruptured plaque(blocked blood vessel in the heart)

…Rupture, fissuring, or ulceration complete ruptureاو , plaque ,ulcerationعلى ال ( fissuring)له درجات اما بكون مجرد شروخ بسطه ruptureوهذا ال*

…by inducing thrombosis and hemorrhage into the core of plaques can expand plaque volume

دائمة thrombusعن chronicاو, )acute coronary syndrome)عنفه بالمكان thrombiؤدي ل Acuteهذا االمر قد كون • Atherosclerosisالحدوث ف ال

Vulnerable plaques (more likely to rupture)

• large atheromatous cores

• thin overlying fibrous caps

• lesions with a paucity of smooth muscle cells (more collagen) or large numbers of inflammatory cells (more metalloproteinases & collagen degradation)

MMPsتساهم ف زادة صنع ال inflammatory cellال

ECM Deposition , Inhibit MMPs , fibrosisتساهم ف smooth muscle cellsال

عن ه degradation of ECMبزد ال smooth muscle cellsطغت على inflammatory cellsاذا الvulnerable plaque

• Unfortunately: two thirds of ruptured plaques are 50% stenotic or less before plaque rupture, and 85% exhibit initial stenotic occlusion of 70% or less

…it is impossible to predict plaque rupture in any given patient

اكثر هذا دل على انه احنا ما بنقدر نتوقع متى بصر ال ruptureانه بصر plaqueمش بالضروره كل ما كبرت ال •rupture

Clinical syndromes Angina pectoris (chest pain)

… stable (10 min) *necrosis (20-30 min)*

unstable --due to superimposed thrombus (plaque rupture) , embolus or

spasm (on rest + no response to drugs )

90% thrombosis of vesseles ( increase the size of plaque due to thrombosis (fixed plaque))

- prinzmetal…typically but not necessarily at atherosclerotic plaques

painؤدي ل coronary ف vasospasm مجرد

وهو اصال ما عنده prinzmetal anginaوعنده young person اللها عن ممكن اشوف specific ولكن مش atherosclerosisبج ف حاالت atherosclerosis

MI (30 min – hours )

Acute heart failure عن فجاه الخالا ماتت وفجأه انقطع الsupply عن القلب والجسم فصار left sided h.failure ممكن تتطور لacute pulmonary edema وممكن ؤدي الىcarcinogenic shock

Sudden cardiac death The most common cause of death due to MI after hospitalization is acute heart failure

The most common cause of death due to MI before hospitalization is ventricular fibrillation (electrical imbalance)

Angina pectoris

= intermittent chest pain caused by transient, reversible myocardial ischemia

Ischemia Not necrosis --- no enzymes in blood

• ischemia-induced release of adenosine, bradykinin, and other molecules that stimulate the autonomic afferents…pain

• 3 types:

-Typical or stable angina

-Prinzmetal or variant angina …nitroglycerin and calcium channel blockers are good

-Unstable angina (also called crescendo angina)

Pains occurs with progressively increasing frequency تصاعدا

Myocardial infarction (ACUTE CORONORY SYNDROM)

-commonly called: heart attack

-necrosis due to ischemia

…1/3 die and ½ before hospital ) نص الثلث بتكون الوفاه قبل الدخول للمستشفى )

…10% before 40 years

…45% before age 65

-The vast majority of MIs are caused by acute coronary artery thrombosis

- In 10% of MIs:

…transmural infarction occurs in the absence of occlusive atherosclerotic vascular disease

-coronary artery vasospasm

-embolization from mural thrombi (e.g., in the setting of atrial fibrillation) or valve vegetations

atrial fibrillation (no visible P waves on ECG fibrillation) اكثر حاله تؤدي الى , mural thrombi قد تكون سبب لحدوثMI من دونatherosclerosis سابق

• Occasionally, subendocardial MI…thrombus/embolus may be absent

Subendocardial MI

Innermost area of the myocardium ه ابعد نقطه عنepicedial artery , اذا كانت * 1متى بتحدث ؟؟ Thrombus مفاجئه مش كبره لدرجة انها تعملtransmural MI

miعله ؤدي ل loadفبكون القلب مش واصلله تروه منحه عن اقل coronary artery عن ف كل افرع ال severe diffuse atherosclerosis بتحب تج ف حاالت ال * 2subendocardial

MI, cont’d

• An atheromatous plaque is suddenly disrupted by intraplaque hemorrhage or mechanical forces, exposing subendothelial collagen and necrotic plaque contents to the blood

Rupture of plaque like endothelial injury (Virchow's triad)

• Platelets adhere, aggregate, and are activated, releasing thromboxane A2, adenosine diphosphate (ADP), and serotonin(vasoconstriction)—causing further platelet aggregation and vasospasm

• Activation of coagulation by exposure of tissue factor and other mechanisms adds to the growing thrombus

• Within minutes, the thrombus can evolve to completely occlude the coronary artery lumen

MI and angiography • Angiography performed within 4 hours of the onset of MI demonstrates coronary

thrombosis in almost 90% of cases

• When angiography is performed 12 to 24 hours after onset of symptoms, however, evidence of thrombosis is seen in only 60% of patients…even without intervention

• so: early thrombolysis and/or angioplasty is effective

thrombusساعات بظهر عندهم ال 4من الحاالت خالل % 90ف

لذلك imaging(angiography)منهم بتظهر عندهم بال % 60فقط , النها بتتحلل thrombus ساعه ال ظهر عنده ال 24_12بعد

. ساعات 4بكون ع االغلب فقط فعال خالل اول ( thrombolytic)العالج

blocked your major arteries to dissolve blood clots that have acutely Thrombolytic drugs #

# y catheter arthroplast(القسطرة )

عن شبكة بتروح على مكان االنسداد وبتفتح المسار stentوبدخلوا coronaryلعند ال femoral arteryبدخلوا صبغة باالشعه من خالل

# CABGheart (bypass)surgery-open)) اذا كان االنسداد بالثالث شران

MI, sequence of events

-1-2 minutes after ischemia: loss of contractility…”stunned

myocardium” for days even after reperfusion…may cause transient

cardiac failure

( Contractility(loss of function )عن الشخص عنده فقط مشكلة ال MIحتى لو لحقنا المرض قبل ما دخل ف مرحلة stunned myocardium (transient heart failure)وعالجناه بس بضل الام عنده مشكلة تسمى

-20-30 minutes: cell death(necrosis)

-2-3 hours: by EM

-6-12 hours: by LM

MI, vessels involved

• proximal left anterior descending (LAD) artery is the cause of 40% to 50% of all MIs

…results in infarction of:

-the anterior wall of the left ventricle

-the anterior two thirds of the ventricular septum

-most of the heart apex

…more distal occlusion of the same vessel may affect only the apex

• acute occlusion of the proximal left circumflex (LCX) artery (seen in 15% to 20% of MIs) will cause necrosis of the lateral left ventricle

• proximal right coronary artery (RCA) occlusion (30% to 40% of MIs) affects much of the right ventricle

• The posterior third of the septum and the posterior left ventricle are perfused by the posterior descending artery

…The posterior descending artery can arise from either the RCA (in 90% of people) or the LCX

• The coronary artery—either RCA or LCX—that gives rise to the posterior descending artery and thereby perfuses the posterior third of the septum is considered the dominant vessel

…right dominant heart VS left dominant

• Occasionally coronary occlusions are encountered in the left main coronary artery…widow maker

سالمتك وتعش left main coronary artery عن اذا انضرب ال ( window marker) صانع االرامل

• Intramyocardial branches are rarely involved

• Remember collaterals between epicardial vessels

Posterior descending artery غذي الposterior third of the septum والposterior wall of left ventricle

Posterior descending artery طالع منright coronary artery من % 10وleft circumflex وعلى هاد االساس بكون

left dominant اوright dominant

Patterns of MI

• Transmural(ECG changes)

ECG changes appear in transmural MI more than subendocardial MI

• Subendocardial

• Microscopic…small vessel occlusions

-vacuities Amyloidosis والدكتور ذكر ال

-embolization of valve vegetations or mural thrombi

-vessel spasm due to elevated catecholamines—either endogenous (e.g.,

pheochromocytoma or extreme stress), or exogenous (e.g., cocaine).

Lab investigations

• CK-MB creatine-kinase MB in 24-48 hours (1 to 2 days) it reaches its peak and it goes back to its normal level in 72 hours

Total CK isn't specific many things cause its increase, so MB is what concern us

• Troponin I and troponin T reaches the peak in 2 days and lasts for 7-10 days

Complications • Contractile dysfunction

…cardiogenic shock occurs in roughly 10% of patients with transmural MIs and typically is associated with infarcts that damage 40% or more of the left ventricle one of these happens: 1.immediate death cardiogenic shock 2.stunned myocardium: transient after HF because of problems in contractility treated the patient and his condition is stable 3.chronic ischemic heart disease :permeant ventricular failure after surviving the MI, because the heart is damaged and weak it could be left HF will result in pulmonary edema and dyspnea , or right HF according to which site of the heart was affected

• Papillary muscle dysfunction it will effect the valve, because its function to close the valve

…post infarct mitral regurgitation

• Myocardial rupture 1-5% it’s rare but frequently fatal

If it is going to happen it is probably going to happen in first week 3-7 days why?? Because the inflammation is in its most powerful state and the beginning of granulation, after that the fibrosis will lower the chances of the rupture happening Fibrosis will make the wall thinner and weak and could have aneurysm (fibroses doesn’t thicken the wall as the rest of the body) but it will prevent the rupture Prefers age older than 60 years, anterior or lateral wall infarctions , female gender, lack of left the most common site of rupture is the free wall of the left ventricle

People who doesn’t hypertrophy have the risk of rupture. If someone has ventricular hypertrophy because of a previous problem he has a better chance surviving the rupture, and first MI (as scarring associated with prior MIs tends to limit the risk of

myocardial tearing) if it’s the first MI to happen, the risk is higher to develop a rupture, but if it was an MI after a series of MIs It lowers the risk, because of the fibrosis that happens after each one

Complications, con’d

• Arrhythmias:

…90% almost always

…in STEMI more than non-STEMI ( ST elevation MI) It could be a simple one, or be a very serious one

… The risk of serious arrhythmias causes death before hospitalization (e.g., ventricular fibrillation) is

greatest in the first hour (its worst phase) and declines thereafter

• Pericarditis inflammation surrounding the heart as a result of the necrosis of the heart that it reaches the pericardium

After 2- 3 days, clinically: pericardial (fraction) rub, at the end of inspiration the doctors hares a tick on the Stethoscope Inflammation of membranes always results in a rub : pleuritis pleuritis rub

• Chamber dilation

• Ventricular aneurysm late, after fibrosis

• Chronic ischemic heart disease : a part of the heart is destroyed and this causes HF in some patients

Differences • Large transmural destroyed 3 layers infarcts are associated with a higher

probability of cardiogenic shock, arrhythmias, and late CHF worse than sub endocardial

• Patients with anterior transmural MIs are at greatest risk for free wall rupture, expansion, formation of mural thrombi, and aneurysm formation more than posterior MI

• Posterior transmural infarcts are more likely to be complicated by serious conduction blocks block in rhythm ECG , right ventricular involvement followed by

right HF, or both

• Patients with anterior infarcts have a much worse clinical course (prognosis) than those with posterior infarcts

• Sub endocardial infarcts, thrombi may form on the endocardial surface because

the damage is accumulated sub endocardially, but the following rarely occur in subendocardial infarcts and happens more in the transmural infarct: pericarditis because the outer layers are affected so it’s easier to reach pericardium , rupture the

wall is weaker, and aneurysms the wall is weaker