Cardiology

Ischaemic Heart Disease

Introduction

  • Ischaemic myocardium is due to insufficient blood supply to match myocardial oxygen demand and can be due to Coronary artery narrowing which may be due to atherosclerosis - obstructive plaques, or complicated plaques with thrombosis (99% of cases), Coronary artery spasm or very rarely Vasculitis.
  • Coronary flow may also be affected by high wall stress imp and large myocardial bulk with large oxygen demands such as with severe aortic stenosis also cause angina or Hypertrophic cardiomyopathy. Severe anaemia can precipitate myocardial ischaemia.

Atherosclerosis

Fatty streaks and progression
  • First grossly pathologically visible sign is the "fatty streak" which lies just below the endothelium. It can be seen in adolescents and young adults.The fatty streak can progress to an atheromatous plaque containing cholesterol and cholesterol esters, necrotic debris, foam cells.
  • As atherosclerosis progresses the plaque can gradually obstruct the lumen and can ulceration with overlying thrombosis formation. The plaque fibrous cap can rupture releasing thrombogenic debris causing localised thrombosis in situ which can embolise downstream or occlude the local lumen.
  • Be aware of the concept of the stable vs unstable plaque.
Unstable plaques
  • is one that for one reason or other is more likely to become a complicated plaque with superficial ulceration or rupture and release of thromboegnic material and luminal obstruction. This can lead to total or subtotal coronary occlusion and myocardial infarction/angina/sudden cardiac death
  • This process is seen in medium sized arteries and similar processes can be found in internal carotid arteries, renal vessels and such. Fatty plaques can be found in the aorta as well as vessels to the lower limbs.
  • Infective aetiologies have been suggested. There is some correlation between minor CRP elevation and atherosclerosis suggesting an inflammatory basis.
  • There is some evidence that statins 'stabilise' unstable plaques.

Risk factors

  • Age (atherosclerosis increases with age)
  • Male (premenopausal women protected until menopause)
  • Smoking - direct correlation
  • Hypertension - relates to systolic and diastolic pressures
  • Family history (1st degree relative with MI/Angina aged under 50)
  • Diabetes
  • Dyslipidaemia - correlates LDL-Choleseterol and total cholesterol. Inversely related to HDL
  • High fibrinogen
  • Physical inactivity
  • Alcohol - "J" shaped curve. Low dose good, then harmful in increasing amounts
  • Obesity

Clinical manifestations of IHD can be summarised as

  • Asymptomatic e.g. found at PM, death from other cause
  • Stable angina
  • Unstable angina
  • Non ST elevation MI
  • ST elevation MI
  • Arrhythmia
  • Sudden cardiac death
  • Ischaemic cardiomyopathy

Stable Angina

  • The most benign form. Pain and exercise have a relationship that is stable. It suggests a fixed stable plaque. Clinically chest pain is of limited duration and severity and occurs after a fixed episode of exertion and is not worsening
  • Investigations such as ECG are useful as baseline and may be normal or may well show ischaemic changes with pain. Cardiac biomarkers e.g. CKMB, troponins by definition are normal.
  • Management includes Aspirin 300 mg then 75 mg od, Nitrates and GTN Sublingual for pain or Long acting e.g. Isosorbide mononitrate, Beta blockade, calcium antagonists e.g. Diltiazem.
  • Ongoing symptoms suggest cardiology review and possible angiography may be considered and PCI/CABG

Acute coronary syndrome

  • In the past decade the term Acute coronary syndrome has become used to describe patients with chest pain of suspected cardiac origin. It is a general term for patients with new or increasing symptoms with associated ECG changes.
  • Stable angina is not included as an ACS and rarely presents acutely where it is more likely to be USA. ECG changes of ST elevation separate the two forms of myocardial infarction as studies have shown that this separates those who benefit from thrombolysis and those that don't.
  • Biomarkers separate the diagnosis of USA from NSTEMI and are not always available or elevated acutely.

Acute coronary syndromes include

  • Unstable angina (USA)
  • NSTEMI
  • STEMI

The differentiation is simple. ST elevation or new LBBB automatically gives the diagnosis of STEMI and urgent PCI/thrombolysis is needed. If there is no ST elevation but ST changes and convincing chest pain then a troponin is done at 12 hours post maximal pain and if elevated the diagnosis is NSTEMI and if normal the diagnosis is USA. So to recap STEMI is diagnosed immediately wit the ECG, NSTEMI and USA cannot be diagnosed until troponin results are back.

Differentials

  • Syndrome X : Recurrent chest pain suggestive of IHD. Worse with exertion. Normal coronary arteries. Recurrent symptoms but good prognosis
  • Coronary spasm : "Printzmetal's angina". ST segment elevation seen sometimes. Coronary arteries normal. Given nitrates and calcium channel blockers - good prognosis
  • Takotsubo Cardiomyopathy: Also known as "broken heart syndrome". Possibly due to elevated catecholamine response to stress leading to myocardial stunning. Anginal chest pain, dyspnoea and evidence of heart failure often in a setting of severe emotional or physiological stress. ECG ST elevation, Q wave and T wave changes, Long QT. Troponin may be raised. Echo - generalized akinesis of the apex and mid ventricle with hypokinesis and wall motion problems beyond the area of one coronary artery. Left ventriculogram shows apical ballooning. Supportive management and the condition resolves over several months.

Unstable angina (USA)

  • Chest pain that is of unlimited duration and/or increasing severity and occurs after at reducing levels of exertion or at rest and may be worsening.
  • Cardiac biomarkers are normal.
  • ECG - Normal or ST depression and T wave changes associated with symptoms
  • Management is the same as NSTEMI so see below

Non ST elevation MI (NSTEMI)

  • Chest pain that is of sometimes severe and may occur at rest or with minimal exertion.
  • ECG may show ST depression and T wave changes suggesting ongoing ischaemia. Cardiac biomarkers are mildly elevated. Pathologically there is subtotal coronary occlusion. Q waves do not develop on the ECG. Q waves suggest transmural infarction.
  • NSTEMI are generally smaller infarcts than STEMI. The issue is to prevent an NSTEMI developing into a STEMI. ST Elevation MI
  • Pathologically due to vessel occlusion from a ruptured plaque with thrombosis and perhaps distal embolisation with coronary artery occlusion.
  • Chest pain that is severe and at rest.
  • ECG - ST elevation, T wave inversion, Q wave formation. The ECG is crucial here and helps tell us what blood vessel is blocked "the culprit lesion" depending on the leads with ST elevation. This can be confirmed at angiography.

ST elevation MI (STEMI)

  • Current Definition of Myocardial infarction 2007 - Evidence of myocardial necrosis in a setting of myocardial ischaemia where there is evidence of one of the following
  • Positive troponin (or equivalent) > 99th percentile + evidence of myocardial ischaemia suggested by
    • Ischaemic symptoms
    • ECG changes of ischaemia - ST-T changes or new LBBB
    • New pathological Q waves
    • Imaging / Echo evidence of loss of viable myocardium by imaging or echo
  • Sudden unexpected cardiac death (Troponin may not be available)
    • Cardiac arrest + symptoms of ischaemia and new ST elevation of new LBBB
    • Evidence of fresh thrombus at angiography before death
  • In the setting of PCI there needs to be a 3 x 99th percentile reading for troponin diagnoses a PCI relatd MI. Baseline troponin normal
  • In the setting of CABG needs a 5 x 99th percentile reading for troponin diagnosis of a CABG related MI

Risk assessment

For patients with STEMI the decision is for urgent PCI or thrombolysis. For the rest with USA/NSTEMI the decision is geared on what is the risk of this patient doing badly and for this there are several scoring systems. For those at high risk PCI a more interventionalist strategy may be considered ether acutely or early in the clinical recovery phase.

Scoring systems include

TIMI Risk Score for USA/NSTEMI can be done by hand

  • Age = 65 years? Yes +1
  • > 3 Risk Factors for CAD? Yes +1 (HTN,Smoker,Chol,DM,FHX)
  • Known CAD (stenosis = 50%)? Yes +1
  • Aspirin use in the past 7days ? Yes +1
  • Severe angina (= 2 episodes < 24 hrs)? Yes +1
  • ST changes = 0.5mm? Yes +1
  • + Cardiac Marker? Yes +1
  • Risk score 0-7.
  • A score of 6-7 = 41% risk at 14 days of: all-cause mortality, new or recurrent MI, or severe recurrent ischaemia requiring urgent revascularization.

Global Registry of Acute Coronary Events score (GRACE scoring) - see textbooks for more.

  • Age
  • Heart rate
  • Systolic BP
  • Creatinine
  • Killip class (heart failure)
  • Cardiac arrest at admission
  • Elevated biomarkers
  • ST segment deviation

Comparing acute coronary syndromes

NSTEMI vs STEMI - The table below shows some of the differences in MI with and without ST segment elevation

NSTEMI STEMI
ECG changes ST depression ST elevation
Vessel 30-40% occluded 80% occluded
Mortality Low in hospital, Higher after discharge with greater 1 year mortality high in hospital, Lower after discharge with lower 1 year mortality
Clot high in platelets high in fibrin

Thrombolysis

No, possibly harmful Indicated, reduces mortality

Investigations of IHD

ECG changes

  • Unstable angina - Normal or ST depression and T wave changes associated with symptoms
  • NSTEMI - ECG may show ST depression and T wave changes suggesting ongoing ischaemia. Q waves do not develop on the ECG.
  • STEMI - ST elevation > 1mm in two limbs leads and > 2mm in two or more contiguous chest leads / Often with reciprocal ST depression, ST-T changes, T wave flattening, T wave inversion New Q waves develop over time and ST segments fall but classically remain up with development of aneurysm. ECG Localisation of MI
    • Inferior leads - II, III, aVf (right coronary artery)
    • Anteroseptal - V1-V3 (LAD)
    • Anterior V1-V6 (LAD)
    • Anterolateral V1-V6, aVL (LAD)
    • Posterior - ST depression V1 and V2 and Dominant R wave (RCA or a Dominant LCx)
  • The ECG especially at rest or between pain may be normal in a patient with significant IHD. It may show minimal changes even with pain. However you must evaluate a patient in the context and character and severity of symptoms and risk factors for IHD and not just on the ECG

Cardiac biomarkers

  • Reflect the amount of damage caused with myocardial infarction and an elevated troponin is a marker for increased mortality.
  • Small rises maybe due to myocardial pathology other than IHD such as transient arrhythmias, myocarditis and pulmonary embolism
    • Myoglobin peaks first at 6 hrs but is non-specific and rarely used.
    • Troponin T and I peak at 6-12 hours and stays elevated for 2 weeks and is the most common marker used.
    • CK peaks at 24 hours. CKMB isoform more cardio-specific and has become less used in the past 10 years.
    • AST which peaks at 24-48 hours and LDH which peaks at 72 hours are mentioned historically and are very non specific as they are elevated in tissue damage such as MI or muscle damage
    • Very sensitive cardiac biomarkers have made the identification of myocyte necrosis more common and has meant that may be labelling some as having Myocardial infarction who would never otherwise have been given this diagnosis as CK was normal.
    • The American and European cardiac groups have deemed any rise in Troponin to be labeled as myocardial infarction whereas the British Cardiac society calls a troponin T rise of between 0.1 to 1 as ACS with myocyte necrosis and MI is when the troponin T > 1 mcg/ml.
    • Initial management however does not wait upon a cardiac biomarker tests but on clinical findings and ECG changes. Any rise even small in Troponin is associated with a worse prognosis.
    • Typical findings

      • Unstable angina - Normal
      • NSTEMI - troponin T > 1 mcg/ml.
      • STEMI - troponin high

Two-dimensional echocardiography in ACS

  • Has become a useful bedside technique in the triage of patients with acute chest pain where the diagnosis might be in doubt with indeterminate ECG changes.
  • Regional wall motion abnormalities occur almost instantaneously after coronary occlusion and well before necrosis. However, wall motion abnormalities are not always specific for STEMI and may be due to ischaemia or an old infarction.

Management

  • ECG should be done urgently to identify STEMI from the other causes.
  • Opiate analgesia e.g. Diamorphine 2.5-5 mg IV. (or morphine 5-10 mg od) to render patient pain free.
  • Oxygen 40-60% unless there are COPD concerns and GTN spray given.
  • A troponin should be sent initially and at 12 hours. Cardiac monitoring.
  • Patient should either go to the cardiac catheterisation lab for PCI or Thrombolysis(STEMI) in A&E/CCU.
  • Aspirin 300 mg stat chewable + 75 mg po od for ACS/MI. Continue long term if ACS confirmed.
  • Clopidogrel 300 mg stat + 75 mg od for all ACS and MI. Continue for 3/12 in NSTEMI and 1/12 in STEMI. Prolonged courses may be needed if stented.
  • Primary percutaneous coronary intervention
    • STEMI: Patients with an ST elevation acute coronary syndrome should be treated immediately with primary percutaneous coronary intervention. Where PCI not available within 90 minutes of diagnosis for STEMI consider Thrombolysis - chose of either streptokinase or reteplase (Streptokinase 1.5 Million units in 100 mls of 5% dextrose or 0.9% saline given over 60 mins). PCI gives patencies of > 90% and without risk of thrombolysis such as haemorrhagic stroke.
    • NSTEMI : Clinically appropriate procedure for patients with Unstable angina or NSTEMI at high risk of death, MI or other cardiac events. High-risk patients with non-ST elevation acute coronary syndrome should be treated with an intravenous glycoprotein IIb/IIIa receptor antagonist, particularly if they are undergoing percutaneous coronary intervention.
  • Thrombolysis - Patients presenting with STEMI within six hours of symptom onset, who fail to reperfuse following thrombolysis, should be considered for rescue percutaneous coronary intervention. Patients with ST elevation acute coronary syndromes treated with thrombolytic therapy should be considered for early coronary angiography and revascularisation. Patency rates with thrombolysis about 60%.
  • Low molecular weight heparin. Fondaparinux is given and LMWHs work by binding to antithrombin III.
  • IV Beta Blockade and then oral to lower rate to 50/min e.g. Metoprolol can reduce ischaemia and likelihood of infarction. Reduce infarct size in NSTEMI and reduce mortality.
  • ACE Inhibitor or ARB drugs should be commenced day 2 and continued long term if any suggestion of LV dysfunction
  • Patients with clinical myocardial infarction and diabetes mellitus or marked hyperglycaemia (>11.0 mmol/l) should have immediate intensive blood glucose control. This should be continued for at least 24 hours.
  • Statins should be started acutely

Cardiac Thrombolysis

Indications

  • An STEMI when PCI can not be carried out within 90 minutes.
  • Check ECG criteria and exclusion criteria. Chest pain started less than 6 hours ago

ECG Criteria

  • 2mm ST elevation in two contiguous chest leads
  • 1 mm ST elevation in 2 or more limb leads
  • New LBBB or Evidence of Posterior MI e.g. ST elevation in v4R or new dominant R wave V1**

Risks

  • The main risk factor from thrombolysis is that of bleeding. Intracerebral haemorrhage is seen in less than 1%. There are however absolute and relative contraindications which must be gone through with the patient.
  • Absolute contraindications
    • Haemorrhagic stroke or stroke of unknown origin at any time, Ischaemic stroke in preceding 6 months
    • CNS trauma or neoplasms, Recent major trauma/surgery/head injury (within preceding 3 weeks)
    • GI bleeding within the last month, Known bleeding disorder, Aortic dissection, Non-compressible punctures (e.g. liver biopsy, lumbar puncture)
  • Relative contraindications
    • TIA in preceding 6 months, Oral anticoagulant therapy
    • Pregnancy or within 1 week post-partum
    • Refractory hypertension (systolic blood pressure >180 mmHg and/or diastolic blood pressure >110 mmHg)
    • Advanced liver disease, Infective endocarditis
    • Active peptic ulcer, Refractory resuscitation

Thrombolytic agents

  • The first agent that had widespread usage for the treatment of STEMI was streptokinase. This was combined with aspirin 300 mg and the landmark trial (ISIS-2) showed that both had an almost equal additive beneficial effect on mortality post STEMI. There has never been any evidence that any thrombolytic agent is beneficial in NSTEMI possibly because the artery is patent and the pathophysiology is different. Newer agents have been developed and we currently use Tenecteplase.
  • Streptokinase (SK) 1.5 million units over 30-60 min i.v. Cannot be used if given before due to formation of neutralising antibodies. Can cause hypotension. Raise foot of bed and give some N-Saline if needed.
  • Tenecteplase (TNK-tPA) Single i.v. bolus. 30 mg if < 60 kg, 35 mg if 60-70 kg, 40 mg if 70-80 kg, 45 mg if 80-90 kg and 50 mg if > 90 kg

Setting where anticoagulation with ACS protocol or thrombolysis can be potentially very harmful in the setting of chest pain and care needs to be taken

  • Aortic dissection (even the most careful clinicians can thrombolyse a dissection as the clinical picture can be so ACS like)
  • Acute pericarditis can cause a haemopercardium
  • Collapse with ST changes can be due to haemorrhagic intracerebral pathology e.g. SAH
  • Syncope with non specific ECG changes and no Chest pain or other signs of ischaemia
  • Head trauma associated with collapse

Percutaneous coronary intervention

Diagnostic percutaneous catheter

  • Femoral route via femoral artery to iliacs to abdominal aorta and then thoracic and arch and even into the left ventricle
  • Radial artery is becoming a more popular route. Catheter passes along Brachial, subclavian and aortic arch down to the coronaries
  • The catheter is then threaded into the ostia of in turn right and left coronary arteries and radiocontrast dye given under x-ray imaging.
  • Identifies and records coronary anatomy and any lesions
  • Dye can also be injected into the LV which will show LV function and aortic valve regurgitation
  • The information provided can help the clinician decide the need for medical therapy alone or plus either PCI or CABG or Valve replacement if that is the pathology

Intervention

  • This can be done at the same time or planned for later
  • A a fine wire can be passed into the artery and past the occlusive lesion via the coronary artery catheter and over this an angioplasty balloon can be threaded which could be inflated by an obstructive lesion. The problem was local damage, arterial dissection and subsequent restenosis and in some cases acute closure of the vessel (which could mean urgent bypass required). These made this a risky business. This was reduced by the use of stents
  • Stents are mesh like tubes which splint the vessel open and reduce these complications. Stents are now indicated in almost all coronary interventions where there is identifiable disease causing symptoms. Newer bare metal and drug eluting stents contain agents that reduce acute stent thrombosis and vascular smooth muscle growth. They require prolonged courses of antiplatelets.

Additional agents

  • With primary PCI : Aspirin Oral dose of 150-325 mg. Clopidogrel Oral loading dose of at least 300 mg, preferably 600 mg. GPIIb/IIIa inhibitors Abciximab: i.v. bolus of 0.25 mg/kg bolus followed by 0.125 mg/kg per min infusion (maximum 10 mg/min for 12 h)
  • With fibrinolytic treatment: Aspirin Oral dose of 150-325 mg. Clopidogrel Loading dose of 300 mg if age <75 years; 75 mg if age>75.
  • Without reperfusion therapy. Aspirin Oral dose of 150-325 mg and Clopidogrel Oral dose of 75 mg

Complications of ST Elevation MI

  • Cardiac rupture into the pericardium with tamponade and death usually after the first few days as the necrotic wall softens. Clinically causes EMD.
  • Pulmonary embolism due to DVT. Should be reduced by use of LMWH.
  • Reinfarction if there is plaque rethrombosis with vessel occlusion. Consider urgent thrombolysis or repeat PCI. Discuss with local centre.
  • Pulmonary oedema. Treat with IV diuretics e.g. Furosemide 50-100 mg IV. Suggests LV impairment and poor prognostic marker.
  • Cardiogenic shock - again suggests poor prognosis and suggests severe loss of LV myocardial muscle mass.
  • RV Infarction: Volume loading treats the apparent hypotension, raised JVP and clear lung fields with an inferior STEMI. Echo is useful and evidence of a Right coronary artery infarction on ECG. Tall R wave in V1. ST elevation in V4R.
  • Ventricular septal rupture can occur and present as heart failure with a loud PSM. Treat as failure. Echo to confirm. May require IABP. Surgery within 48 hours.
  • Papillary muscle rupture can occur acutely with breathlessness and a loud pansystolic murmur. There may be acute severe MR with marked pulmonary oedema. Echo to confirm. Usually seen with a small infarct of the posteromedial papillary muscle in RCA or Cx distribution. Benefit from IABP as bridge to surgery. Cardiac surgical assessment for MVR within 48 hours.
  • Atrial fibrillation is not uncommon and is treated with digoxin (ensure potassium over 4 mmol/l) or amiodarone for rate control. Rhythm control can be attempted through drugs such as amiodarone or DC cardioversion may be contemplated. Warfarin should be considered.
  • Ventricular tachycardia often seen acutely during ischaemia/infarction. Treat with IV lidocaine, IV amiodarone if persistent VT. Ensure normal potassium and magnesium. DC shock if compromised to return to sinus rhythm
  • Sinus bradycardia seen with inferior MI. Withhold beta blockade and Give atropine and consider Isoprenaline if persists. Temporary basis if compromise remains
  • Second/Third degree AV Block: Consider Atropine and External pacing. Temporary pacing wire may be needed. Avoid subclavian route if on anticoagulants.
  • First degree heart block: Needs no treatment. If associated with new onset LBBB it may suggest widespread anterior wall infarction and pacing may be needed.
  • Dressler's syndrome occurs weeks after and is an autoimmune response following a transmural infarct. Treat with NSAIDS/Steroids. Percutaneous coronary intervention

Cardiac surgery

There is still a role for Coronary artery bypass grafting though it has been reduced by PCI. In many t is a very effective and successful procedure giving pain relief and improving prognosis. It may be a primary procedure for some or carried out after failed PCI and stenting or where the lesions are too high risk for PCI. The indications are those with

  • Left Main stem stenosis > 70%
  • Proximal LAD stenosis > 70%
  • Triple vessel disease stenosis > 70%

Those with diabetes or Poor LV function are at higher risk but have most to gain. The operation is usually done on cardiopulmonary bypass through a median sternotomy. The plan is to bypass the existing stenotic lesions using either

  • Left internal mammary grafted into the LAD beyond the stenosis. Arterial grafts have better long term patency.
  • Reversed (they have valves) saphenous vein grafts from the legs to bypass coronary obstructive lesions.

A post CABG patient is left with sternal wound and visible scars where veins stripped on lower legs if a reversed saphenous vein graft (SVG) was used. Using LIMA grafts can impair wound healing.

Secondary prevention for IHD

  • Smoking cessation
  • BP control
  • Aspirin 75 mg od long term
  • Beta blockers long term - reduced myocardial oxygen demand
  • Cholesterol lowering Simvastatin 40 mg od
  • Cardiac rehabilitation
  • Manage diabetes
  • Exercise program and weight reduction
  • Medical Management of Angina Despite PCI and surgery some continue to have angina symptoms.
  • Other anti-anginal Medications include
    • Nitrates - acts to increase Nitric oxide which relaxes vascular smooth muscle cells
    • Potassium channel blockers e.g. nicorandil