Ischaemic Heart Disease

Ischaemic Heart Disease

·        Most common cause of death in Western countries

·        Incidence peaked in NZ in 1968 at 320 deaths /100,000. Now 200/100,000

·        In NZ, 4,500 acute MI per year, 3,200 CIHD per year (=25% of all deaths)

·        Risks factors:

o  Cigarette smoking 5.2 x

o  Hypertension 3.3 x

o  Hyperlipidaemia 3.7 x

o  Diabetes mellitus

o  Male gender

o  Family history

·        Pathogenesis

o  Myocardial blood flow < metabolic demand of myocardium

o  Coronary perfusion related to:

§  Atherosclerosis occluding coronary arteries (fixed coronary stenosis), acute plaque changes (eg rupture), thrombosis, vasoconstriction

§  Differential between ostia (aortic diastolic pressure) and coronary sinus (right atrial pressure)

§  Compression of intramuscular arteries during contraction ® myocardium perfused in diastole

§  Decreased coronary blood flow also due to ­intraventricular pressure & myocardial contraction, aortic valve stenosis/regurgitation, ­right atrial pressure

·        Cross sectional area of major vessels must be reduced by 75% to significantly affect perfusion

Hypertension

·        See Measuring Blood Pressure(Topic), for measurement

·        Is a risk factor not a disease

·        Definition:

o   No dividing line between normal and high blood pressure. There are arbitrary levels set based on the risk of complications (the main ones being stroke, MI, heart failure and renal failure)

o   In determining whether the blood pressure is „bad‟, take into account the systolic and diastolic pressure, age, sex, other diseases (eg DM, hyperlipidaemia), smoking. Older age is the greatest risk factor: treat high blood pressure in an older person regardless of other risk factors

o   WHO definitions:

o   Also classified according to retinopathy, see Hypertensive Retinopathy(Topic)

·        Classified as:

o   Primary/essential (what most people have – but a diagnosis of exclusion): contributing factors include hereditary, obesity, alcohol intake, salt intake (60% of patients respond to ¯salt intake – but compliance difficult)

o   Secondary causes: renal disease (eg renal artery stenosis, diabetic kidney disease, etc), endocrine (eg ­cortisol, ­aldosterone, acromegaly, oral contraceptives), neurogenic (eg psychogenic), sleep apnoea (major changes in baroreceptor reflexes)

·        Epidemiology:

o   Prevalence ­ with age. Older people at greater risk at any given blood pressure compared with young

o   Strong risk factor for stroke, congestive heart failure, coronary artery disease and renal failure

o   Probably 10 – 20% of older adults require treatment (ie have essential hypertension with diastolic pressure > 95 mmHg)

o   Treatment reduces related complications. Stroke risk reduces in line with BP, MI risk doesn‟t reduce as much for a given drop in BP

·        History:

o   How accurate is the diagnosis?

o   Usually symptomless

o   Possibly related symptoms: palpitation, flushing, headache

o   Related risk factors: history of renal, cardiac or neurological disease

o   Asthma, diabetes, gout, renal disease: complications with drug treatment

o   Occupational

o   Diet: salt, fat

o   Smoking and alcohol

o   Family History

·        Detection and assessment:

o   Blood pressure more labile in older adults Þ measure 2 to 3 times (in same arm). Measure standing and sitting

o   In primary hypertension usually ­ on standing.  In secondary hypertension, usually ¯ on standing

o   Basic workup:

§  Urine for protein, blood and glucose ® DM, renal disease

§  FBC for polycythaemia, renal disease, alcohol

§  Electrolytes (especially K): exclude odd endocrine causes

§  ECG: any end organ damage

o   Additional tests if indicated:

§  Microscopic analysis of urine (for casts)

§  Plasma lipids

§  Blood glucose: need to modify drug treatment

§  Serum Ca, PO4, uric acid (gout – associated with hypertension, may also ­ due to drugs)

§  Echocardiogram or CXR

§  Special tests for secondary causes if indicated: eg renal imaging, 24 hour urine for catecholamine metabolites (phaeochromocytoma)

·        Pathology:

o  Pathophysiology: poorly understood. Older people have ¯renin, and are more responsive to Na depletion. „Hardening‟ of arteries ®­systolic pressure. ¯Responsiveness to b-mediated vascular relaxation

o  Leads to hypertensive heart disease: left ventricular hypertrophy ® relative myocardial ischaemia. Aortic valvular disease also ® LV hypertrophy

o  Malignant hypertension (accelerated hypertension): hypertension leading to rapidly progressive vascular compromise. Blood vessels show fibrinoid necrosis or concentric hyperplasia („onion skin‟ changes)

Non-drug treatment

·        Remove/substitute drugs: eg NSAIDs, OCP, Prednisone

·        Always attempt lifestyle changes first:

o  Stop smoking (little effect on BP, but biggest impact on risk factors)

o  Weight loss

o  ¯Alcohol (max 2 drinks per day)

o  ¯Salt intake (max 70 mmol/day)

o  ­exercise

o  ¯Saturated fats

Drug Treatment

·        When to treat:

o  Given it is such a strong risk factor, consider hypertension above systolic 140 mmHg

o  Always treat > 170 systolic or > 110 diastolic

o  Hardly ever treat < 140 and < 90 diastolic 

o  In between, controversial. Consider other risks. If over 65 no other risk factors needed (eg diabetes, etc). Give considerable attention to non-pharmacological approaches for 3 – 6 months. Long term follow up necessary 

o  Treat 72 older adults for 5 years to prevent 1 death, treat 43 for 5 years to prevent one cerebrovascular event 

o  Aim of treatment: diastolic < 90

·        Rules of thumb:

o  Use low doses of several agents, rather than increasing doses of one drug (especially thiazides) 

o  First line: thiazides (with or without a potassium sparing agent) and/or b-blocker (atenolol most used in trials). If tolerate them both then add them together 

o  ACE inhibitors: not so effective but rated best quality of life

o  Don‟t take diuretic, ACE inhibitor and NSAIDS together (renal side effects)

o  Introduce slowly, monitor for symptoms and postural hypotension

o  Aim for 140/90, and then attempt back titration 3 monthly

·        Individualise depending on co-morbid conditions:

Angina Pectoris

·        Symptom complex characterised by attacks of chest pain, causing ischaemia but not infarction

·        Patterns:

o   Stable angina (typical): pain on exertion, relieved by rest or vasodilators. Subendocardial ischaemia with ST-segment depression

o   Variant or Prinzmetal‟s angina: classically occurs at rest. Caused by reversible spasm in normal to severely atherosclerotic coronary arteries. Can see ST-segment elevation or depression

o   Unstable angina: variable, prolonged pain, pain at rest or worsening of pain in stable angina.  ST-  segment depression – but may be elevated. Most common complication: arrhythmias (especially VF). Within 3 months 4% will have sudden death and 15% a myocardial infarct

o   Sudden cardiac death. Usually within an hour of a cardiac event or without symptoms. Usually high-grade stenosis. Usually associated with arrhythmias, especially ventricular ectopic beats and subsequent VF

·        Treatment options for stable angina:

o   Nitrates: short & long acting

o   b-blockers (¯myocardial O2 consumption)

o   Ca antagonists

o   Aspirin

·        Unstable angina:

o   = Acute Coronary Syndrome (ACS) = acute heart problems without ST elevation

o   Investigations:

§  ECG.  Serial or continuous if high risk

§  Bloods: Troponin (repeat after 6 hours), FBC, Cr, electrolytes, CK, blood glucose. Want to test lipids/cholestrol – but false positives following an acute coronary event. Do later.

§  CXR: cargiomegaly?  Pulmonary oedema?  Dissection?

o   Medical therapy:

§  Aspirin: reduces progression to MI. Neither Warfarin nor Heparin confers little further benefit. Use heparin if high risk.

§  b-blockers: reduce progression to MI

§  iv nitroglycerine for symptomatic relief

§  Maybe calcium channel blockers that reduce the heart rate

o   Low risk:

§  Normal ECG and no detectable troponin despite ­angina frequency or severity

§  Management: discharge for outpatient assessment

o   High risk:

§  If even a minor degree of ST depression or a significant elevation of troponin ® minor myocardial damage so now is the time to act

§  Overlap between High Risk ACS and non-STEMI (non-ST elevation MI)

§  Management: Admit for coronary angiography and, if positive, early percutaneous coronary intervention (ie more aggressive treatment than previously)

·        Long term management:

o   ¯Obesity, diabetes, smoking, ­exercise

o   Referral to a cardiac rehabilitation programme

o   Statins if serum cholesterol raised

o   ACE inhibitors if hypertension or diabetes

Myocardial Infarction (MI)

Definition and Classification

·         Old WHO definition: two out of three of: chest discomfort for > 30 minutes, enzyme rise and typical pattern of ECG involving the development of Q waves (ie normal ECG does not rule out infarction)

·        New definition: Blood levels of sensitive and specific markers are raised in the clinical setting of acute ischaemia (ie ­importance of biochemical tests). See Laboratory Diagnosis(Topic)

·        2 classifications:

o  ST elevation MI verses none (ie STEMI and non-STEMI). Often ST elevation progresses to Q wave

o  Q wave verses none (older classification) Þ transmural or not

Epidemiology

·        Same risk factors as for atherosclerosis

·        5% occur under age 40, 45% over age 65

·        Oestrogen protective in women pre-menopause

·        30% mortality with 20% dying before admission

Symptoms

·        Crushing chest pain (absent in 15% of cases).  But < 25% with chest pain have an MI

·        Can also present as epigastric, arm, wrist, or jaw discomfort with exertion or at rest

·        May be associated with dyspnoea, sweating, nausea, vomiting, weakness, dizziness, fainting

Pathogenesis

·        Irreversible damage in 20 – 40 minutes

·        Occlusive intracoronary thrombus, overlying ulcerated or stenotic plaque:

o  Causes 90% of transmural acute MIs.

o  For blood to clot need: abnormal flow, damage to vessel wall and clotting factors.

o  Thrombis formation: activated platelets adhere to exposed collagen of damaged endothelium ® release thromboxane A2 ® expanding platelet mass + coagulation

·        Vasospasm: with or without atherosclerosis. Postulate where no findings at post-mortem (10%) – but many of these will be thrombi that have lysed

·        Emboli: from left sided mural thrombosis, vegetative endocarditis

·        Arteritis: polyarteritis nordosa, Kawasaki disease

·        Other: dissecting aneurysm occluding coronary ostia, ¯O2 supply (anaemia, CO, cyanide), ­O2 demand (hyperthyroidism, fever)

Gross Morphology

·        Transmural infarct: entire thickness of wall from endocardium to epicardium. Usually Anterior wall (50%) or posterior free wall/septum in 15 – 30%. Q wave

·        Subendocardial infarct: multifocal necrosis confined to inner 1/3 to ½ of left ventricle wall. More commonly associated with temporary hypoperfusion (eg shock). No Q wave

·        Occlusion:

o  LAD: 40 – 50%

o  RCA: 30 – 40%

o  LCA: 15 – 20%

·        Gross changes over time:

o   18 – 24 hours    Pallor of myocardium – anaemic, grey brown (cf normal brown-red)

o   24 – 72 hours    Pallor (yellow/brown) with increasingly defined hyperaemia border

o   3 – 7 days           Hyperaemic border (darker brick red) with central yellowing,

·        haemorrhagic areas

o   10 – 21 days      Maximally yellow and soft with vascular margins (red edge – granulation

·        tissues moves in)

o   7 weeks   White fibrosis

Microscopic Appearance

o   C    – 3 hours      Wavy myocardial fibres

o   2    – 3 hours      Staining defect with tetrazolium

o   4    – 12 hours    Coagulative necrosis with loss of cross striations, oedema, haemorrhage,

·        early neutrophil infiltrate (WBCs with multilobed nuclei), loss of

·        myocardial striations

Laboratory Diagnosis

·        Troponins:

o   Increases highly specific for MI injury – but not synonymous with MI or ischaemia, but probably indicates irreversible injury

o   Increases above the 99^th percentile are significant (lower than previously)

o   Prognosis related to degree of elevation

o   Rises no faster than CK (ie starts to rise within 3 – 12 hours) and more expensive but substantial rise after MI (400 fold)

o   Causes besides MI:

§  Subendocardial injury from wall stress in left ventricular hypertrophy (eg heart failure)

§  Right ventricular injury in severe PE

§  Direct trauma (eg contusion)

§  Toxic injury by drugs or in septic shock

§  Myocarditis

§  Cardioversion

o   Troponin T

§  = Cardiac troponin T, cTnT, TnT: only available from Boehringer Mannheim

§  Normal < 0.03 mg/l

§  Increases in renal failure due to ¯clearance (Þ false positive)

o   Troponin I:

§  Everyone else‟s test.  Normal value depends on which assay is used

§  I remains elevated for 5 – 9 days and T for 2 weeks. Better marker for recent MI than LDH. Harder to interpret in re-infarct – don‟t know whether it‟s the 1st or 2^nd infarct

o   Test on admission to either see if already raised (poor prognosis) or to establish baseline

·        CK – total: not specific to myocardial injury. Do baseline and use to check for reinfarction (Troponins not so good for this)

·        Older tests:

o   CK – MB fraction:

§  MM fraction is in both skeletal and myocardial muscle. But 15 – 40% of cardiac CK is MB, compared with 2% skeletal. BB found in brain, bowel and bladder. The MB fraction is therefore very specific

§  MB fraction rises within 2 – 8 hours. Dissipates within 1 – 3 days. So also a good marker of reinfarction

§  CK – MB isoforms: Ratio of isoform 2 to isoform 1 > 1.5 Þ early acute MI (changes before CK- MB elevated). Requires electrophoresis, so labour intensive. False positives with heart failure

o   Myoglobin: Oxygen binding protein in skeletal and cardiac muscle. Elevated before CK-MB, but is not specific to cardiac muscle. Negative myoglobin can help rule out MI

o   LDH: supplanted by other tests. Rises later (24 – 48 hours) and elevated for 7 – 14 days. Isoenzyme measurement of LDH 1 and 2 necessary for cardiac specificity

o   AST and ALT: intermediate timing but rather non-specific

·        Other Investigations: CXR, echo, ABG, FBC, ?perfusion scan, ?amylase  <

Management

·        Exclude differentials:

o   Aortic dissection

o   Pericarditis

o   PE or other causes of pleuretic chest pain

o  Peptic ulcer

·        Investigations as for Unstable Angina(Topic)

·        They will be frightened.  Reassure.  > 90% survival if low risk (< 60, no diabetes, no past history, pulse <100)

·        High flow O2 (unless CO2 retaining)

·        Morphine 5 – 15 mg iv at < 1 mg/min (+ antiemetic eg metoclopramide 5 – 10 mg iv). Effects: analgesic, anxiolytic, anti-arrhythmic, venodilatory

·        Restoring/Maintaining vessel patency:

o  Aspirin 300 mg (unless contra-indicated)

o  Thrombolysis:

·        Indicated if with 12 hours of MI

·        Best within 60 mins

·        Contraindications:

o   General bleeding tendency: warfarin, haemophilia, severe liver disease, thrombocytopenia

o   Local bleeding risk: Past haemorrhagic stroke or recent surgery, prolonged resuscitation (® rib fractures, contusion, etc), peptic ulcer, GI bleeding, pregnancy, cavitating Tb

o   Severe hypertension (systolic > 200, diastolic > 120)

o   Pre-existing thrombis that might embolise (eg endocarditis, aortic aneurysm)

·        Options:

o   Streptokinase: restores perfusion in 30%

o   TPA: restores perfusion in 54%. Expensive. Use tPA if previous reaction to SK, or if SK has been used between 1 year and 5 days ago

·        Complications: 1% risk of stroke

·        Watch this space for platelet receptor blocking drugs (eg IIb/IIIa inhibitors)

o  Consider for primary angioplasty (acute stenting of an occluded coronary artery) if large anterior infarct refractory to thrombolysis

·        Management of preload, afterload and heart rate and rhythm:

o  Glyceryl trinitrate

o  ACE inhibitor + b-blocker (unless contra-indicated)

o  Bed rest

·        Monitor ECG, BP, cardiac enzymes, ABGs

·        Stop smoking

·        Early stress/treadmill test

Prognosis

·        Good prognostic indicators:

o  No pre-existing hypertension

o  Normal heart size

o  No post MI pulmonary oedema

o  No significant arrhythmias after day 1

o  No post-MI angina

·        If good prognosis, discharge on aspirin and b-blocker. Add an ACE inhibitor if ¯LVF. Consider a statin if ­lipids.

Complications

·        35% die within one year, 10% per year thereafter.  NZ overall hospital mortality 19%

·        Arrhythmias and conduction defects: eg premature ventricular beats, sinus bradycardia, VT, VF, heart block

·        Extension of infarction, re-infarction

·        Congestive heart failure (pulmonary oedema): everyone who‟s had a significant MI will have some degree of this

·        Cardiogenic shock: if more than 40% of the left ventricle is infarcted.  70 – 90% die

·        Pericarditis: fibrinous adhesions in the pericardium overlying the infarct (Dressler‟s syndrome – autoimmune adherent pericarditis – occurring 2 – 6 weeks post MI or cardiac surgery. Treatment - steroids)

·        Mural thrombosis ® embolisation

·        Myocardial rupture ® tamponade. Maximum incidence day 5 - 7. Can include rupture of interventricular septum

·        Papillary muscle rupture or infarct ® mitral incompetence

·        Ventricular aneurysm formation: 12 – 20% of cases

·        Ischaemic cardiomyopathy: severe atherosclerosis involving all major branches ® inadequate vascular supply ® myocyte loss and interstitial fibrosis ® ¯compliance & dilation ® compensation by myocyte hypertrophy ® slow progressive heart failure and enormous heart size (up to 2 to 3 times normal)

·        Time to complications:

o   1 – 3 days: arrhythmia, CHF, pericarditis

o   5 – 7 days: rupture

o   Later: recurrent MI, angina, embolism from mural thrombosis, mitral regurgitation, Dressler‟s syndrome (Post MI syndrome)