ISCHEMIA

1

• ISCHEMIC HEART DISEASE/CORONARY ARTERY DISEASE

Dr.W.C.Lwabby (MMed, MD)Lecturer Int. Med. Dpt
2
Introduction

• Ischemic heart disease (IHD)/CORONARY ARTERY
  DISEASE(CAD)
• Is a condition in which
• there is an inadequate supply of blood and
  oxygen to a portion of the myocardium.
• Occurs when there is an imbalance between
  myocardial oxygen supply and demand.
• Common cause of myocardial ischemia is
  atherosclerotic disease of a coronary artery,
• sufficient to cause a regional reduction in
  myocardial blood flow.

3
Introduction

• Disease of the coronary arteries is almost always
  due to
• atheroma and its complications, particularly
  thrombosis.
• Occasionally, the coronary arteries are involved
  in other disorders such as
• Aortitis
• Polyarteritis
• Other connective tissue disorders.

4
Introduction

• Patients with IHD fall into two large groups
• Chronic CAD (stable angina)
• Acute coronary syndromes (ACSs)
• Is a term that encompasses both unstable angina
  and myocardial infarction (MI).

5
Anatomy of the coronary vessels

• Two main coronary arteries, branches of ascending
  aorta.
• Left coronary arteries
• supply  LA, LV and the anterior wall of the RV.
• Right coronary arteries
• supply RA,  RV as well as the SA node.

6
Anatomy of coronary arteries
7
EPIDEMIOLOGY

• gt 60 of the global burden of IHD occurs in
  Developing countries.
• It increases with age.
• Men gt women, but CAD is the leading cause of
  death in both men and women

8
RISK FACTORS OF IHD

• Generally include
• Hypertension
• Elevated LDL /VLDL cholesterol
• Reduced HDL cholesterol
• Oxidant stress caused by cigarette smoking
• Excess angiotensin II
• Obesity
• Insulin resistance
• Diabetes mellitus

9
PATHOPHYSIOLOGY

• The underlying pathophysiological mechanisms for
  IHD begin with the process of atherosclerosis,
• In ACS
• Atherosclerosis can be described as a low-grade
  inflammatory state of the intima of medium-sized
  arteries.
• It develops and progresses for decades prior to
  the acute event.
• This is accelerated by the risk factors, such as
• Hypertension, Hyperlipidemia, smoking,
  diabetes, and genetics.

10
PATHOPHYSIOLOGY..

• This slow progression leads to the gradual
  thickening of the intima,
• which may over time narrow the lumen of the
  artery to various degrees.

11
Stable angina

• Angina pectoris
• Is the symptom complex caused by transient
  myocardial ischaemia
• It constitutes a clinical syndrome rather than a
  disease.
• It may occur whenever there is an imbalance
  between myocardial oxygen supply and demand.
• Coronary atheroma is by far the most common
  cause.
• Coronary perfusion is impaired by fixed or stable
  atheroma of the coronary arteries.

12
Clinical features

• Stable angina is characterized by
• Central chest pain (retro-sternal chest pain)
• Discomfort
• Radiating to left( right) shoulder/arm/ neck/jaw
• Precipitated by exertion or other forms of stress
• Promptly relieved by rest or Nitrates.
• Brief duration, lasting lt10-15 min
• Associated with breathlessness, diaphoresis,
  nausea, anxiety

13
Clinical features

• Physical examination
• Is frequently unremarkable.
• Should include a careful search for evidence of
• Valve heart disease (particularly aortic)
• Important risk factors (e.g. hypertension,
  diabetes mellitus)
• Left ventricular dysfunction (cardiomegaly,
  gallop rhythm)
• Other manifestations of arterial disease (carotid
  bruits, peripheral vascular disease)
• Unrelated conditions that may exacerbate angina
  (anaemia, thyrotoxicosis).

14
Diagnosis

• The history is the most important factor in
  making the diagnosis.
• Investigations
• The ECG may show evidence of previous MI but is
  often normal
• Coronary arteriography
• This provides detailed anatomical information
  about the extent and nature of coronary artery
  disease.

15
Treatment

• Specific Treatment
• Antiplatelet therapy
• Aspirin -Low-dose (75 mg)
• Reduces the risk of adverse events such as MI.
• Clopidogrel (75 mg daily)
• Is an equally effective antiplatelet agent.
• Can be prescribed if aspirin causes troublesome
  dyspepsia.

16

• Anti-anginal drug treatment
• Five groups of drug are used to relieve or
  prevent the symptoms of angina
• Nitrates
• ß-blockers
• Calcium antagonists
• Potassium channel activators
• an If channel antagonist.

17

• Nitrates
• Act directly on vascular smooth muscle to produce
  venous and arteriolar dilatation.
• Their beneficial effects are due to
• Reduction in myocardial oxygen demand (lower
  preload and afterload)
• Increase in myocardial oxygen supply (coronary
  vasodilatation).
• Sublingual glyceryl trinitrate (GTN)
• Administered from
• a metered-dose aerosol (400 µg per spray) or
• as a tablet (300 or 500 µg), will relieve an
  attack of angina in 23 minutes.
• Side-effects include headache, hypotension,
  syncope.
• Other nitrates (isosorbide dinitrate , isosorbide
  mononitrate )

18

• Beta-blockers
• These lower myocardial oxygen demand by
• reducing heart rate, BP and myocardial
  contractility
• They may provoke bronchospasm in patients with
  asthma.
• Non- cardioselective ß-blockers may aggravate
  coronary vasospasm by
• blocking the coronary artery ß2adrenoceptors.
• so a once-daily cardioselective preparation is
  used (e.g. metoprolol 50200 mg daily, bisoprolol
  515 mg daily).

19

• Calcium channel antagonists
• They lower myocardial oxygen demand by
• reducing BP and myocardial contractility.
• Dihydropyridine calcium antagonists, (nifedipine
  and nicardipine), often cause a reflex
  tachycardia.
• This may be counterproductive and it is best to
  use them in combination with a ß-blocker.
• Verapamil and diltiazem
• Are suitable for patients who are not receiving
  a ß-blocker (e.g. those with airways obstruction)
  because
• Slow SA node firing
• Inhibit conduction through the AV node
• Tend to cause a bradycardia.

20

• Invasive treatment
• Percutaneous coronary intervention (PCI)
• Is performed by passing a fine guidewire across a
  coronary stenosis under radiographic control.
• using it to position a balloon, which is then
  inflated to dilate the stenosis.
• Coronary artery bypass grafting
• The internal mammary arteries
• radial arteries or
• reversed segments of the patients own saphenous
  vein can be used to bypass coronary artery
  stenoses

21
Acute coronary syndrome (ACS)

• Is a term that encompasses both
• Unstable angina(UA)
• Myocardial infarction (MI) -(NSTEMI, and STEMI).
• It is characterized by
• New-onset or rapidly worsening angina (crescendo
  angina) or,
• Angina on minimal exertion or,
• Angina at rest in the absence of myocardial
  damage.

22
Introduction..

• An ACS may present as a new phenomenon or against
  a background of chronic stable angina.
• The culprit lesion is usually a complex ulcerated
  or fissured atheromatous plaque with
• Adherent platelet-rich thrombus
• Local coronary artery spasm.
• This is a dynamic process whereby the degree of
  obstruction may either
• Increase, leading to complete vessel occlusion,
  or
• Regress due to the effects of platelet
  disaggregation and endogenous fibrinolysis.

23
Myocardial infarction

• Myocardial infarction (MI) occurs when
• Symptoms occur at rest.
• There is evidence of myocardial necrosis, as
  demonstrated by an elevation in cardiac
  biomarkers (troponin or CK-MB isoenzyme).
• STEMI occurs when
• Coronary blood flow decreases abruptly after a
  total thrombotic occlusion of a coronary artery,
  previously affected by atherosclerosis.
• A coronary artery thrombus develops rapidly at a
  site of vascular injury resulting into STEMI.
• The injury is produced or facilitated by factors
  such as cigarette smoking, hypertension, and
  lipid accumulation.

24
Myocardial infarction..

• The diagnosis of NSTEMI, is established if a
  patient with the clinical features of UA
  develops
• Evidence of myocardial necrosis, as reflected in
  elevated cardiac biomarkers (CKMB / Troponin).
• NSTEMI is caused by
• a reduction in oxygen supply and/or
• an increase in myocardial oxygen demand
  superimposed on a lesion that causes partial
  coronary arterial obstruction, usually an
  atherothrombotic coronary plaque.

25
UNSTABLE ANGINA(UA)

• Is caused by
• dynamic (partial) obstruction of a coronary
  artery due to plaque rupture with superimposed
  coronary thrombosis and spasm.
• Occurs even at rest or with minimal exertion
• More severe and lasts longer than stable angina,
  may be as long as 30 minutes
• May not disappear with rest or use of angina
  medication
• May lead to complete occlusion of vessel causing
  MI.

26
Clinical features of ACS

• Chest Pain
• Is the cardinal symptom of an ACS.
• Occurs in the same sites as angina but is usually
  more severe and lasts longer
• it is often described as a tightness, heaviness
  or constriction in the chest.
• In acute MI
• the pain can be excruciating
• Breathlessness, vomiting and collapse
• Are common features.
• Most patients are breathless and in some, this is
  the only symptom.

27
Clinical features of AClinical features of
ACSCS cont

• Vomiting and sinus bradycardia
• are often due to vagal stimulation and are
  particularly common in patients with inferior MI.
• Nausea and vomiting may also be caused or
  aggravated by opiates given for pain relief.
• Syncope
• If syncope occurs, it is usually due to an
  arrhythmia or profound hypotension.

28

Clinical features of ACS

• Painless or silent MI
• Indeed, MI may pass unrecognized.
• Is particularly common in older patients or those
  with diabetes mellitus.
• Sudden death
• From ventricular fibrillation or asystole
• May occur immediately and often within the first
  hour.
• The development of cardiac failure reflects the
  extent of myocardial ischaemia.
• Cardiac failure is the major cause of death in
  those who survive the first few hours.

29

• Physical Exam (in large area of myocardial
  ischemia)
• Diaphoresis
• Pale
• Cool skin
• Sinus tachycardia
• Hypotension
• a third and/or fourth heart sound basilar rales

30
Diagnosis

• The assessment of ACS depends heavily on
• Analysis of the character of the chest pain and
  its associated features.
• Evaluation of the ECG.
• Serial measurements of biochemical markers of
  cardiac damage.

31
Investigations

• Electrocardiography(ECG)
• Is central to confirming the diagnosis.
• The earliest ECG change is usually ST-segment
  elevation.
• With proximal occlusion of a major coronary
  artery
• ST-segment elevation (or new bundle branch block)
  is seen initially
• later diminution in the size of the R wave
• In Transmural (full-thickness) infarction
• There is development of a Q wave.
• Subsequently, the T wave becomes inverted because
  of a change in ventricular repolarisation.

32

33
(No Transcript)
34

• Electrocardiography(ECG).
• In NST segement elevation there is
• Partial occlusion of a major vessel
• Complete occlusion of a minor vessel
• This causing unstable angina or partial-thickness
  (subendocardial) MI.
• This is usually associated with ST-segment
  depression and T-wave changes.
• In the presence of infarction
• this may be accompanied by some loss of R waves
  in the absence of Q waves.

35

• Plasma cardiac biomarkers
• These biochemical markers are
• Creatine kinase (CK), a more sensitive and
  cardio-specific isoform of this enzyme is
  -CK-MB.
• Troponins T and I -the cardio-specific proteins.
• In unstable angina (UA)
• There is no detectable rise in cardiac biomarkers
  or enzymes.
• The initial diagnosis is made from the clinical
  history and ECG only.
• In contrast MI
• causes a rise in the plasma cardiac biomarkers or
  enzymes, that are normally concentrated within
  cardiac cells.
• The change in plasma concentrations of these
  markers confirms the diagnosis of MI.

36

• CK
• Starts to rise at 46 hours
• Peaks at about 12 hours and falls to normal
  within 4872 hours.
• Is also present in skeletal muscle
• a modest rise in CK (but not CK-MB) may
  sometimes be due to
• An intramuscular injection
• Vigorous physical exercise
• The most sensitive markers of myocardial cell
  damage are the troponins T and I
• These are released within 46 hours and remain
  elevated for up to 2 weeks.

37

• Chest X-ray
• This may demonstrate pulmonary oedema that is not
  evident on clinical examination.
• The heart size is often normal, but there may be
  cardiomegaly due to pre-existing myocardial
  damage.
• Echocardiography
• Is useful for assessing ventricular function and
  for detecting important complications, such as
• Mural thrombus
• Cardiac rupture
• Ventricular septal defect
• Mitral regurgitation and
• Pericardial effusion.

38
Treatment

• Immediate treatment
• Analgesia
• Is essential, not only to relieve distress but
  also to lower adrenergic drive and there by
  reduce
• vascular resistance,
• BP
• Infarct size and
• Susceptibility to ventricular arrhythmias.
• Intravenous opiates ( morphine sulphate 510 mg
  or diamorphine 2.55 mg)
• OXYGEN THERAPY

39

• Antithrombotic therapy
• Antiplatelet therapy
• Aspirin
• Oral administration of 75325 mg aspirin daily
• improves survival, with a 25 relative risk
  reduction in mortality.
• The first tablet (300 mg) should be given orally
  within the first 12 hours.
• Clopidogrel
• In combination with aspirin
• The early (within 12 hours) use of Clopidogrel
  (600 mg, followed by 150 mg daily for 1 week and
  75 mg daily thereafter)
• This confers a further reduction in ischaemic
  events.

40

• Anticoagulants
• Reduces the risk of thromboembolic complications
• Prevents re-infarction in the absence of
  reperfusion therapy or after successful
  thrombolysis.
• Can be achieved using
• Unfractionated heparin
• Fractioned (low-molecularweight) heparin

41

• Anti-anginal therapy
• Nitrates
• Sublingual glyceryl trinitrate (300500 µg)
• Is a valuable first-aid measure in UA or
  threatened infarction
• I/V nitrates (glyceryl trinitrate 0.61.2 mg/hr
  or isosorbide dinitrate 12 mg/hr)
• are useful for the treatment of LV failure and
  the relief of recurrent or persistent ischaemic
  pain.

42

• ß-blockers
• I/V ß-blockers (e.g. atenolol 510 mg or
  metoprolol 515 mg given over 5 mins)
• Relieve pain
• Reduce arrhythmias
• Improve short-term mortality in patients who
  present within 12 hours of the onset of symptoms.
  
• They should be avoided if there is
• HF (pulmonary oedema)
• Hypotension (systolic BP lt 105 mmHg)
• Bradycardia (heart rate lt 65/min).

43

• Calcium channel antagonist
• A dihydropyridine calcium channel antagonist
  (e.g. nifedipine or amlodipine)
• This can be added to the ß-blocker if there is
  persistent chest discomfort but may cause
  tachycardia if used alone.
• verapamil and diltiazem
• Because of their rate-limiting action, these are
  the calcium channel antagonists of choice if a
  ß-blocker is contraindicated

44

• Fibrinolysis
• Fibrinolytic therapy should ideally be initiated
  within 30 min of presentation.
• The principal goal prompt restoration of full
  coronary arterial patency.
• The approved fibrinolytics
• Tissue plasminogen activator (tPA),
  streptokinase, tenecteplase (TNK), and reteplase
  (rPA)
• Promote the conversion of plasminogen to plasmin,
  which subsequently lyses fibrin thrombi.

45

• Interventional Cardiology
• Percutaneous coronary intervetion (PCI)
• Is a procedure that's used to open a blocked or
  narrowed coronary arteries.
• Improve blood flow to heart, relieve chest pain,
  and possibly prevent a heart attack.
• Sometimes a small mesh tube (stent) is placed in
  the artery to keep it open after the procedure.
• Antiplatelet admin. post stent
• Aspirin for life
• Clopidogrel for at least 6wks for metal stent

46

• Coronary artery by pass grafting (CABG)
• To improve blood flow to the myocardial tissue
  that are at risk for
• Ischemia
• Infarction as a result of the occluded artery.
• Arteries or veins from elsewhere in the patient's
  body are grafted to the coronary arteries to
  bypass atherosclerotic narrowings
• This improves the blood supply to the coronary
  circulation supplying the myocardium.

47
Long-term Treatment

• Risk factor modification eg. cessation of
  smoking
• Lipid lowering drugs ( e.g. statins,fibrates)
• ACE inhibitors are recommended for long-term
  plaque stabilization.
• Antiplatelet therapy,
• Now recommended to be the combination of
  aspirin and clopidogrel for at least 912 months,
  then continue with aspirin to prevent rupture of
  plaque.

48
References

• Brian R,Walker N,Stuart H. Davdsons Principle
  and Practice of Medicine 22nd Edition.CORONARY
  ARTERY DISEASE,Pg 583-600.
• KASPER F,HAUSER LONGO. HARRISONS PRINCIPLES OF
  INTERNAL MEDICINE 19th Edition. Ischemic Heart
  Disease pg 1998-2004.

49

• THANK YOU