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8 C A R D I O V A S C U L A R D I S E A S E the LV. Simultaneous septal and LV epicardial pacing resynchro- nises LV contraction, improving exercise tolerance in selected patients.
CORONARY ARTERY DISEASE
Coronary artery disease (CAD) is the leading cause of premature death in the developed world and is estimated to become, by 2020, the major cause of death worldwide. In the UK 1 in 3 men and 1 in 4 women die from CAD. Disease of the coronary arteries is almost always due to atherosclerosis and its complications, particularly thrombosis. Atherosclerosis is a progressive inflammatory disorder of the arterial wall, characterised by focal lipid-rich deposits of atheroma that remain clinically silent until they become large enough to impair arterial perfusion or until disruption of the lesion results in thrombotic occlusion or embolisation of the affected vessel. The pathogenesis of atherosclerosis is complex but several risk factors have been identified: Age and sex: Age is the most powerful independent risk factor for atherosclerosis. Pre-menopausal women have lower rates of disease than men but thereafter risk is similar. Hormone replacement therapy has no role in prevention of atherosclerosis, however. Family history: A ‘positive’ family history is present when clinical problems occur in first-degree relatives aged < 50 yrs (male) or < 55 yrs (female). Increased risk reflects a combination of shared genetic and environmental (e.g. smoking, exercise, diet) factors. Hypertension: The incidence of atherosclerosis increases as BP (systolic and diastolic) rises. Antihypertensive therapy reduces car- diovascular mortality and stroke. Hypercholesterolaemia: Risk rises with plasma cholesterol concentration. Lowering low-density lipoprotein (LDL) and total cholesterol reduces the risk of cardiovascular events (death, MI, stroke). Diabetes mellitus: This is a potent risk factor for all forms of atherosclerosis and is often associated with diffuse disease. Insulin resistance (normal glucose homeostasis with high levels of insulin) is also a risk factor for CAD. Lifestyle factors: There is a strong, dose-linked relationship between cigarette smoking and CAD. Alcohol is associated with reduced rates of coronary disease, but alcohol excess is associated with hypertension and cerebrovascular disease. Physical inactivity and obesity are independent risk factors for atherosclerosis; regular exercise appears to have a protective effect. Diets deficient in fresh fruit, vegetables and polyunsaturated fatty acids are associated with an increased risk of vascular disease.
Stable angina
Angina pectoris is the symptom complex occurring when an imbal- ance between myocardial oxygen supply and demand causes
8 C A R D I O V A S C U L A R D I S E A S E transient myocardial ischaemia. Coronary atheroma is by far the most common cause of angina; however, the symptom may also be a manifestation of other forms of heart disease, such as aortic valve disease, hypertrophic cardiomyopathy or coronary vasopasm (Prinzmetal’s angina). Occasionally, the coronary arteries are involved in other disorders, such as polyarteritis and other connec- tive tissue disease. Clinical features The history is by far the most important factor in making the diag- nosis of stable angina (p. 201). Stable angina is characterised by central chest pain, discomfort or breathlessness that is precipitated by exertion or other forms of stress, and is promptly relieved by rest. Physical examination is frequently negative but may reveal evidence of: ● (^) Aortic stenosis (an occasional cause of angina). ● (^) CAD risk factors (e.g. hypertension, diabetes; examine for retinopathy). ●^ LV dysfunc- tion (e.g. cardiomegaly). ●^ Other arterial disease (e.g. carotid bruits, peripheral vascular disease). ●^ Conditions that exacerbate angina (e.g. anaemia, thyrotoxicosis). Investigations Resting ECG: This may show evidence of previous MI but is often normal, even in patients with severe coronary artery disease. The most convincing ECG evidence of myocardial ischaemia is obtained by demonstrating reversible ST segment depression or elevation, with or without T-wave inversion, during symptoms. Exercise ECG: The patient’s ECG and BP are monitored during exercise using a standard treadmill or bicycle ergometer protocol. Planar or down-sloping ST segment depression of ≥ 1 mm is indica- tive of ischaemia; up-sloping ST depression is less specific. Exercise testing is also a useful means of assessing the severity of coronary disease and identifying high-risk individuals. However, false nega- tives and positives do occur and the predictive accuracy of exercise testing is lower in women than men. Myocardial perfusion scanning: This is particularly helpful in patients who are unable to exercise or who have an equivocal or uninterpretable exercise test. Scintiscans of the myocardium are obtained at rest and during stress (exercise or pharmacological, e.g. dobutamine) after IV administration of a radioactive isotope that is taken up by viable perfused myocardium. A perfusion defect present during stress but not at rest indicates reversible myocardial ischae- mia; a persistent defect suggests previous MI. Stress echocardiography: This alternative to myocardial perfusion scanning has similar predictive accuracy (superior to exercise ECG). Ischaemic segments of myocardium exhibit reversible defects in con- tractility (on echocardiography) during exercise or pharmacological stress; areas of infarction do not contract at rest or during stress. The technique is particularly useful for identifying areas of viable
8 C A R D I O V A S C U L A R D I S E A S E survival in patients with stable angina. It is mainly used in single or two-vessel disease; coronary artery bypass graft (CABG) surgery is usually the preferred option in patients with three-vessel or left main disease. The main acute complication is vessel occlusion by thrombus or dissection, which may lead to myocardial damage (2–5%) requiring stenting or emergency CABG. The overall mortal- ity risk is < 0.5%. The main long-term complication is restenosis. The routine use of stents in appropriate vessels reduces both acute com- plications and the incidence of restenosis. Drug-eluting stents can reduce this risk even further at the cost of a small risk of late stent thrombosis. In combination with aspirin and heparin, adjunctive therapy with potent platelet inhibitors, such as clopidogrel or glyco- protein IIb/IIIa receptor antagonists, improves the outcome of PCI, with lower short- and long-term rates of death and MI. Coronary artery bypass grafting (CABG): The internal mammary arteries, radial arteries or reversed segments of saphenous vein can be used to bypass coronary artery stenoses, usually under cardio- pulmonary bypass. The operative mortality is ~1.5%, but higher in elderly patients and those with poor LV function or significant comorbidity (e.g. renal failure). There is a 1–5% risk of perioperative stroke. Approximately 90% of patients are free of angina 1 yr after surgery, but < 60% of patients are asymptomatic ≥ 5 yrs after CABG. Arterial grafts have much better long-term patency rates than vein grafts. Treatment with aspirin or clopidogrel improves graft patency, while intensive lipid-lowering therapy slows progression of disease in the native coronary arteries and grafts. Persistent smokers are twice as likely to die in the 10 yrs following surgery compared with those who give up at surgery. CABG improves survival in patients with left main coronary stenosis and those with symptomatic three- vessel coronary disease; the benefit is greatest in those with impaired LV function or positive stress testing prior to surgery.
Acute coronary syndrome
This term encompasses unstable angina and myocardial infarction (MI). Unstable angina refers to new-onset or rapidly worsening (cresc endo) angina, and angina on minimal exertion or at rest without myocardial damage. In MI there are symptoms at rest and myocardial necrosis occurs, leading to partial thickness, non-ST elevation MI (NSTEMI) or full-thickness, ST elevation MI (STEMI). Acute coronary syndrome may present de novo or against a back- ground of chronic stable angina. The underlying pathophysiology is usually a fissured atheromatous plaque with adherent thrombus formation. Clinical features ● (^) Pain: like that of angina but more severe and prolonged. ● (^) Breathlessness. ● (^) Vomiting: due to vagal stimulation, particularly in inferior MI. ●^ Syncope or sudden death due to arrhythmia. ●^ MI may occasionally be painless, especially in diabetic or elderly patients.
8 C A R D I O V A S C U L A R D I S E A S E Investigations The ECG is the most important investigation in the assessment of acute chest pain and guides initial therapy. It shows a characteristic series of changes in MI (Fig. 8.14): The earliest change is usually ST elevation followed by diminu- tion in the size of the R wave, and development of a Q wave (indi- cating full-thickness infarction). Subsequently, the T wave becomes inverted and this change persists after the ST segment has returned to normal. ECG changes are best seen in the leads that ‘face’ the infarcted area. With anteroseptal infarction, abnormalities are found in one or more leads from V 1 to V 4. Anterolateral infarction produces changes from V 4 to V 6 , in aVL and lead I. Inferior infarction is best shown in leads II, III and aVF. Infarction of the posterior wall of the left ventricle does not cause ST elevation or Q waves in the standard leads, but can be diagnosed by the presence of reciprocal changes (ST depression and a tall R wave in leads V 1 –V 4 ). Occa sionally, new- onset LBBB is the only ECG change. Patients with ST elevation or new LBBB block require immediate reperfusion therapy. In patients with unstable angina or NSTEMI, the ECG may show ST/T-wave changes, including ST depression, transient ST elevation and T-wave inversion. These conditions carry a high risk of progression to STEMI or death. Plasma biochemical markers (Fig. 8.15): The plasma concentration of enzymes and proteins normally concentrated within cardiac cells is increased in MI. The most useful markers are creatine kinase (CK) and CK-MB (a cardiospecific isoform) and the cardiac troponins T and I. CK starts to rise at 4–6 hrs, peaks at ~12 hrs and falls to normal within 48–72 hrs. Troponins T and I are released within 4–6 hrs and remain elevated for up to 2 wks.
A B C
D E
Fig. 8.14 The serial evolution of ECG changes in full-thickness myocardial infarction. A Normal ECG complex. B (Minutes) Acute ST elevation. C (Hours) Progressive loss of the R wave, developing Q wave, resolution of the ST elevation and terminal T-wave inversion. D (Days) Deep Q wave and T-wave inversion. E (Weeks or months) Old or established infarct pattern; the Q wave tends to persist but the T-wave changes become less marked.
8 C A R D I O V A S C U L A R D I S E A S E Immediate management: the first 12 hrs Urgent hospital admission is required, as appropriate medical therapy reduces the risk of death and recurrent ischaemia by at least 60%. Initial therapy is summarised in Figure 8.16. Analgesia is essential to relieve distress, and also to lower adren- ergic drive and susceptibility to arrhythmias. IV opiates with an appropriate antiemetic (e.g. metoclopramide) should be titrated until the patient is comfortable. Fig. 8.16 Summary of treatment for acute coronary syndrome (ACS). (GP = glycoprotein; LMWH = low molecular weight heparin) Yes Yes Yes Yes Yes No No No No No Low risk (< 1%) Clinical assessment ECG, troponin Eligible for thrombolysis? Failed reperfusion? Calculate GRACE score Recurrent symptoms? ST elevation ACS? Thrombolysis IV O 2 , ECG monitoring Aspirin 300 mg, ticagrelor 180 mg orally Metoprolol 5–15 mg IV/50–100 mg orally Transfer to specialist cardiology unit Consider primary PCI:
- Available?
- < 120/min?
120/min but ineligible for thrombolysis?
- GP IIb/IIIa receptor antagonist IV
- Emergency PCI Coronary angiography
- Consider GP IIb/IIIa receptor antagonist IV Maintenance in-hospital treatment:
- Aspirin
- Ticagrelor
- Fondaparinux/LMWH
- Statin
- β-blocker
- ACE inhibitor
- Fondaparinux or LMWH SC
- Consider nitrate infusion Medium or high risk
8 C A R D I O V A S C U L A R D I S E A S E Antithrombotic therapy Antiplatelet therapy with oral aspirin (300 mg initially, then 75 mg daily) improves survival (25% reduction in mortality). In combina- tion with aspirin, the early (within 12 hrs) use of clopidogrel (600 mg, then 150 mg daily for a week, then 75 mg daily) confers a further reduction in mortality; however, in acute coronary syndrome, tica- grelor (180 mg, then 90 mg twice daily) is more effective. Anticoagulation reduces thromboembolic complications and rein- farction. The pentasaccharide fondaparinux (2.5 mg SC daily) has the best safety and efficacy profile, but unfractionated or low molec- ular weight heparin is a useful alternative. Anticoagulation should be continued for 8 days or until hospital discharge. Anti-anginal therapy Sublingual GTN is valuable first aid in unstable angina, and IV nitrates are useful for the treatment of LV failure and the relief of recurrent or persistent ischaemic pain. IV β-blockers relieve pain, reduce arrhythmias and improve short-term mortality in patients who present within 12 hrs of the onset of symptoms, but should be avoided if there is heart failure, hypotension or bradycardia. Reperfusion therapy in non-ST elevation MI Immediate reperfusion therapy has no demonstrable benefit and thrombolytic therapy may be dangerous in these patients. Selected medium- and high-risk patients benefit from in-hospital coronary angiography and revascularisation but this does not need to be within 12 hrs. Reperfusion therapy in ST elevation acute coronary syndrome Immediate reperfusion preserves function and improves survival in these patients. Primary percutaneous coronary intervention (PCI): The treatment of choice for STEMI. Outcomes are best when it is used in combina- tion with glycoprotein IIb/IIIa receptor antagonists and intracoro- nary stent implantation. Compared to thrombolytic therapy, it is associated with a greater reduction in the risk of death, recurrent MI or stroke. The use of primary PCI has been limited by availability of this highly specialised emergency service. Thus, IV thrombolytic therapy remains first-line treatment in many hospitals, especially in rural or remote areas. When primary PCI cannot be achieved within 2 hrs, thrombolytic therapy should be administered. Thrombolysis: Helps to restore coronary patency, preserves LV function and reduces the mortality of MI by 25 – 50%. Successful thrombolysis leads to reperfusion with relief of pain and resolution of acute ST elevation. It is indicated only in patients presenting within 12 hrs of the onset of symptoms and with ECG changes of LBBB or ST segment elevation of > 1 mm in the limb leads or 2 mm in the chest leads. The benefit is greatest when treatment is given within the first few hours. Alteplase (human tissue plasminogen
8 C A R D I O V A S C U L A R D I S E A S E Pericarditis This is particularly common on the second and third days following infarction. A distinct new pain develops, which is often positional or exacerbated by inspiration. Opiate analgesics are preferred over non-steroidal and steroidal anti-inflammatory drugs, as the latter may increase the risk of aneurysm formation and myocardial rupture. Dressler’s syndrome is an autoimmune disorder that occurs weeks to months after the infarct and is characterised by persistent fever, pericarditis and pleurisy. Severe symptoms may require treat- ment with an NSAID or corticosteroids. Mechanical complications Papillary muscle rupture: May cause acute pulmonary oedema and shock with a pansystolic murmur due to the sudden onset of severe mitral regurgitation. Emergency mitral valve replacement may be necessary. Rupture of the interventricular septum: Usually presents with sudden haemodynamic deterioration accompanied by a new loud pansystolic murmur. It may be difficult to distinguish from acute mitral regurgitation but tends to cause right heart failure rather than pulmonary oedema. Doppler echocardiography will confirm the diagnosis. Without prompt surgery, the condition is usually fatal. Rupture of the ventricle: Leads to cardiac tamponade and is usually fatal. Other recognised peri-infarct complications These include: ● (^) Systemic embolism from a cardiac thrombus. ● (^) Development of a ventricular aneurysm. Late management Risk stratification and further investigation Scores (e.g. GRACE score) predict early mortality and are used to select patients for intensive therapy. Prognosis of survivors of acute coronary syndrome is related to: Myocardial damage: Damage is assessed by echocardiography early in the recovery phase. Ischaemia: Patients with early ischemia need urgent coronary angiography and revascularisation. Others should undergo an exer- cise tolerance test ~4 wks after the infarct; coronary angiography is required for those with a strongly positive test. Ventricular arrhythmias: During convalescence from acute coro- nary syndrome these may indicate poor ventricular function and risk of sudden death. Although empirical anti-arrhythmic treatment is of no value, selected patients may benefit from specific anti- arrhythmic therapy (e.g. ICDs). Lifestyle and risk factor modification Smoking: Giving up smoking is much the most effective thing a patient can do after acute coronary syndrome, as cessation halves
8 C A R D I O V A S C U L A R D I S E A S E mortality at 5 yrs. Cessation success rates are improved by support- ive advice and pharmacological therapy. Hyperlipidaemia: Lowering serum cholesterol with statins follow- ing acute coronary syndrome reduces the risk of death, reinfarction, stroke and the need for revascularisation. Lipids should be meas- ured within 24 hrs of presentation because cholesterol often falls in the 3 mths following infarction. Irrespective of serum cholesterol, all patients should receive statins after acute coronary syndrome, but those with LDL cholesterol concentrations > 3.2 mmol/L (~120 mg/dL) benefit from more intensive therapy, such as ator- vastatin 80 mg daily. Other risk factors: Maintaining an ideal weight, eating a Mediterranean-style diet, taking regular exercise, and controlling hypertension and diabetes mellitus all improve the long-term outlook. Mobilisation and rehabilitation When there are no complications, the patient can return home in 5 days and gradually increase activity, with the aim of returning to work in 4–6 wks. The majority of patients may resume driving after 4–6 wks. Emotional problems, such as anxiety and depression, are common, and must be recognised and dealt with accordingly. Formal rehabilitation programmes, based on graded exercise protocols with individual and group counselling, are often very successful. Secondary prevention and drug therapy Low-dose aspirin therapy reduces the risk of further infarction and other vascular events by ~25% and should be continued indefinitely. Clopidogrel should be given in addition to aspirin for at least 3 mths and is a suitable alternative in aspirin-intolerant patients. Long-term β-blocker therapy reduces mortality by ~25% in survivors of acute MI and should be prescribed unless there are specific contraindica- tions (p. 745). ACE inhibitors can prevent the onset of heart failure, improve survival and reduce hospitalisation, and should be consid- ered in all patients with acute coronary syndrome. Patients with acute MI complicated by heart failure and LV dysfunction, and either pulmonary oedema or diabetes, further benefit from addi- tional mineralocorticoid receptor antagonism (e.g. eplerenone 25–50 mg daily). ICDs reduce the incidence of sudden cardiac death in patients with severe LV impairment (ejection fraction ≤ 30%) post-MI. Prognosis Of those who survive an acute attack, > 80% live for a further year, ~75% for 5 yrs and 50% for 10 yrs. Early death is usually due to an arrhythmia but, later on, the outcome is determined by the extent of myocardial damage. Unfavourable features include poor LV func- tion, AV block and persistent ventricular arrhythmias. The progno- sis is worse for anterior than for inferior infarcts.
