Cardiology - Ischaemic heart disease Flashcards
What is ischaemic heart disease (IHD)?
IHD is a broad term encompassing several closely related syndromes caused by myocardial ischaemia - an imbalance between cardiac blood supply (perfusion) and myocardial oxygen and nutritional requirements.
Cardiac myocytes generate energy almost exclusively through mitochondrial oxidative phosphorylation, cardiac function is therefore strictly dependent upon the continuous flow of oxygenated blood through the coronary arteries.
What causes IHD? What else can cause cardiac pain?
In more than 90% of cases, IHD is a consequence of reduced coronary blood flow secondary to obstructive atherosclerotic vascular disease. Thus, unless otherwise specified, IHD is usually synonymous with coronary artery disease (CAD).
Less commonly, IHD can also results from
- aortic dissection, hypotension and shock (diminished blood volume)
- paroxysmal tachycardias (increased demand)
- severe anaemia (diminished oxygen carrying capacity), cardiomyopathy, coronary artery embolism (rare) and vasculitis
- pneumonia or CHF (diminished oxygenation)
What are the clinical presentations of IHD?
The manifestations of IHD are a direct consequence of the insufficient blood supply to the heart. The clinical presentation may include one or more of the following cardiac syndromes:
1) Angina pectoris - ischaemia induces pain but is insufficient to cause myocyte death. Angina can be stable (occurring on exertion), unstable (angina of increasing frequency or occurring at rest), Prinzmetal (chest pain caused by coronary artery spasm) or Decubitus (precipitated by lying flat)
2) Acute myocardial infarction - the severity or duration of ischaemia is sufficient to cause cardiomyocyte death and necrosis
3) Chronic IHD with CHF - progressive cardiac decompensation after acute MI or secondary to accumulated small ischemic insults
4) Sudden cardiac death - this can occur as a consequence of tissue damage from MI, but most commonly results from a lethal arrhythmia without myocardial necrosis
What would suggest a non cardiac cause of chest pain?
This would be favoured by pain that is continuous for several days, precipitated by changes in posture or deep breathing, the ability to continue normal activities and lack of relief by rest.
The more common alternatives in the differential diagnosis are oesophageal pain and musculoskeletal pain.
What is the pathogenesis of IHD? How does inflammation, thrombus formation and vasoconstriction play a role?
IHD is primarily a consequence of inadequate coronary perfusion relative to myocardial demand. This imbalance occurs as a consequence of the combination of a pre-existing (“fixed”) atherosclerotic occlusion of coronary arteries, and new, superimposed thrombosis and/or vasospasm.
The following factors are important in the development of coronary atherosclerosis:
i) Inflammation - atherosclerosis begins with the interaction of damaged endothelial cells and circulating leucocytes, resulting in T cell and macrophage recruitment and activation. These cells drive subsequent smooth muscle cell accumulation and proliferation
ii) Thrombosis associated with a disrupted plaque - often triggers the acute coronary syndrome. Partial occlusion by a newly formed thrmbus on a disrupted ahterosclerotic plaque can wax and wane with time leading to unstable angina or sudden death. But, even partial luminal occlusion by thrombus can compromise blood flow sufficiently to case a small infarction of the innermost zone of the myocardium (subendocardial infarct). Organizing thrombi produce potent activators of smooth muscle proliferation, which can contribute to the growth of atherosclerotic plaques
iii) Vasoconstriction - directly compromises lumen diameter and by increasing local mechanical shear forces, vessel spasm can cause plaque disruption. Vasoconstriction in atherosclerotic plaques can be stimulated by (1) circulating adrenergic agonists, (2) locally released platelet contents, (3) imbalance between endothelial cell -relaxing factors (e.g. NO) and contracting factors (e.g. endothelin) and (4) mediators released from perivascular inflammatory cells
What is meant by the term “critical stenosis”?
Fixed obstructions that occlude less than 70% of a coronary vessel lumen typically are asymptomatic, even with exertion. In comparison, lesions that occlude more than 75% of a vessel lumen - resulting in the so called critical stenosis - generally cause symptoms in the setting of increased demand. A fixed stenosis that occludes 90% of more of a vascular lumen can lead to inadequate coronary blood flow with symptoms even at rest - one of the forms of unstable angina.
What is the cause of the majority of acute coronary syndromes?
In most cases, unstable angina, infarction and sudden cardiac death occur because of abrupt plaque change followed by thrombosis. The initiating event typically is sudden disruption of a fixed partially occlusive plaque. More than one mechanism of injury may be involved: rupture, fissuring or ulceration of plaques can expose highly thrombogenic constituents or sub endothlial basement membrane leading to thrombosis. In addition, haemorrhage into the core of plaques can expand plaque volume, which increases luminal occlusion.
What intrinsic factors affect plaque vulnerability?
Factors that trigger acute plaque change are believed to act by increasing the lesions susceptibility to disruption by mechanical stress. Both intrinsic aspects of plaque composition and structure, and extrinsic factors, such as blood pressure and platelet reactivity may contribute as follows:
- plaques that contain large atheromatous cores, or have thing overlying fibrous caps are more likely to rupture and are therefore termed “vulnerable”. Fissures frequently occur at the junction of the fibrous cap and the adjacent normal plaque free arterial segment, where the mechanical stresses are highest and the fibrous cap is thinnest.
- plaques with a lack of smooth muscle cells, or large numbers of inflammatory cells are more vulnerable to rupture (due to the lack of collagen produced by SM cells)
How do extrinsic factors affect plaque vulnerability?
Adrenergic stimulation can put physical stress on the plaque by causing hypertension or local vasospasm. The surge in adrenergic stimulation associated with awakening and rising may underlie the observation that the incidence of acute MI is highest between 6am and 12pm.
What happens to plaques that are disrupted and heal?
Plaque disruption and non occlusive thrombosis are common, repetitive and often clinically silent complications of atheromas. The healing of these subclinical plaques and overlying thrombosis is an important mechanism by which atherosclerotic lesions progressively enlarge and underlies chronic ischaemic heart disease by forming a severe, fixed, stable obstruction.
What is the pathogenesis of stable angina?
Stable angina occurs when coronary blood flow is impaired by a fixed atheroma of the coronary arteries. During exertion, an imbalance between myocardial oxygen supply and demand causes transient myocardial ischaemia.
Coronary atheroma is by far the most common cause of angina, however, the symptom may also be a feature of other forms of heart disease such as aortic valve disease, HOCUM, and coronary vasospasm.
What are the clinical features of stable angina?
The history is by far the most important factor in making the diagnosis of stable angina.
The condition is characterised by central chest pain, breathlessness on exertion and is promptly relieved by rest.
Physical examination is frequently negative, but may reveal evidence of:
- aortic stenosis (an occasional cause of angina)
- CHD risk factors (e.g. hypertension, diabetes)
- LV dysfunction (e.g. cardiomegaly)
- other arterial disease (e.g. bruits, peripheral vascular disease)
- conditions that exacerbate angina (e.g. anaemia, thyrotoxicosis)
- retinopathy (diabetic or hypertensive)
How should stable angina be investigated?
1) Resting ECG
2) Exercise ECG
3) Myocardial perfusion scanning
4) Stress echo
5) Coronary angiography
What does a resting ECG show in stable angina?
This may show signs of previous MI but is often normal, even in patients with left main or severe three vessel 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.
What is involved and when is an exercise ECG performed for stable angina?
The patients ECG and BP are monitored during exercise using a standard treadmill or bicycle protocol. Planar, or down sloping ST segment depression of >1mm is indicative of ischaemia. Up sloping ST segment 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 negatives do occur and the predictive accuracy of exercise testing is lower in women than men.
What is a myocardial perfusion scan?
This is particularly helpful in patients who are unable to exercise test or who have equivocal or uninterpretable exercise tests. Scintiscans of the myocardium are obtained at rest and during stress (e.g. exercise or pharmacological - e.g. dobutamine) after IV administration of a radio-isotope that is taken up by viable perfused myocardium. A perfusion defect present during stress but not at rest indicates reversible myocardial ischaemia; a persistent defect suggests a previous MI.
When are stress echoes performed?
These are an alternative to myocardial perfusion scans but have a similar predictive accuracy. Ischaemic segments of myocardium exhibit reversible defects in contractility (on echo) 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 “hibernating” myocardium in patients with heart failure and CAD being considered for revascularisation.
List risk factors associated with IHD
1) 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. HRT has no role in prevention of atherosclerosis however.
2) FHx - a “positive” family history is present when clinical problems occur in first degree relatives aged <50 years (males) or <55 years (females). Increased risk reflects a combination of genetic and environmental risk factors.
3) Hypertension - the incidence of atherosclerosis increases as BP rises
4) Hypercholesterolaemia - risk rises with plasma cholesterol concentration. Lowering low density lipoprotein (LDL) and total cholesterol reduces the risk of cardiovascular events (death, MI, stroke)
5) Diabetes - this is the most 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
6) Others - obesity, smoking, alcohol, diet
What are the aspects of stable angina management?
- identification and control of risk factors
- symptom control
- identification of high risk patients for treatment and to improve life expectancy
How should risk factors be managed for stable angina?
The most important lifestyle advice is smoking cessation but other steps include regular exercise and aiming for ideal BMI. All patients with CAD should receive statin therapy, irrespective of serum cholesterol. BP should be treated to a target of <140/85 mmHg, although ACEi (unless contraindicated) are of benefit in all patients with vascular disease. Aspirin reduces the risk of adverse events such as MI and should be prescribed indefinitely for all patients with CAD. Clopidogrel is an equally effective alternative in patients who cannot tolerate aspirin.
What drugs are first line for relief of symptoms in stable angina? What is their rationale for use in angina?
The basic aim of drug treatment in angina is to reduce the work of the heart and hence its oxygen demand. The nitrates (e.g. GTN, isosorbide mononitrate, isosorbide dinitrate) are first line drugs. Their main effect is to cause peripheral vasodilatation, especially in the veins, by an action on vascular smooth muscle that involves the formation of NO and an increase in intracellular cGMP. The resulting pooling of blood in the venous capacitance vessels (due to increased venous compliance) reduces venous return and the end diastolic volume is decreased. Reduction in the distension of the heart wall decreases oxygen demand and pain quickly subsides.
GTN is given sublingually to avoid first pass metabolism and is used to treat acute angina attacks. If this is required more than twice per week then combined therapy with a beta blocker or calcium channel blocker may be required.
What are the short and long acting nitrates?
The main short acting nitrate in clinical use is GTN. It is given by sublingual spray and works for about 30mins. It is more useful in preventing attacks than in stopping them once they have started. Patches containing GTN (transdermal patches) have a long duration of action (up to 24h).
Long acting nitrates are more stable and may be effective for several hours depending on the drug and preparation used. Isosorbide dinitrate is widely used, but it is rapidly metabolised by the liver. The use of isosorbide mononitrate, which is the main active metabolite of the dinitrate, avoids the variable absorption and unpredictable first pass metabolism of the nitrate.
What are the adverse effects of nitrates?
The arterial dilatation produced by nitrates causes headache, which frequently limit the dose. More serious side effects are hypotension and fainting. Reflex tacchycardia often occurs, but this is prevented by combined therapy with beta blockers. Prolonged high dosage may cause methaemoglobinaemia as a result of oxidation of haemaglobin.
What is the mechanism of nitrates?
Initial metabolism of these drugs releases NO2-, a process that requires tissue thiols. Within the cell, NO2- is converted into nitric oxide, which then activates guanylyl cyclase, causing an increase in the intracellular concentration of cGMP in the vascular smooth muscle cells. cGMP activates protein kinase G (PKG) an enzyme that causes the vascular smooth muscle to relax by several mechanisms. These include: (i) activation of Ca pumps that sequester Ca++ into the smooth endoplasmic reticulum (SERCA) and extrude Ca++ into the extracellular space (PMCA); and (ii) activation of K+ channels causing membrane hyperpolarization that inhibits Ca++ influx by switching off voltage dependent Ca++ channels. The fall in intracellular Ca++ decreases MLCK activity and relaxation occurs as light chain phosphorylation is reduced by MLC phosphatase, the activity of which is increased by PKG.
What is the rationale for using beta adrenoceptor antagonist in angina?
Beta blockers depress myocardial contractility and reduce the heart rate. In addition to these effects, which reduce the oxygen demand, beta blockers may increase the perfusion of the ischaemic area because the increase in heart rate increases the duration of diastole and hence the time available for coronary blood flow. If necessary, a long acting nitrate is added.
Beta blockers are the standard drug used in angina, but they have many side effects and contraindications. If beta blockers cannot be used, e.g. in patients with asthma, then a calcium channel blocker can be used as an adjunct to short acting nitrates.
Why is the choice of beta blocker important in angina?
Beta blockers are used for the prophylaxis of angina. The choice of drug may be important, intrinsic activity may be a disadvtange in angina and the cardioselective beta blockers such as atenolol and metoprolol are probably the drugs of choice.
How to calcium channel blockers work in angina?
These drugs are widely used in angina and have fewer side effects than beta blockers. CCBs inhibit L-type voltage sensitive Ca++ channels in arterial smooth muscle causing relaxation and vasodilatation. Preload is not significantly affected. Calcium channels in the myocardium and conducting tissue are also affected by CCBs, which produces a negative inotropic effect by reducing Ca++ influx during the plataeu phase of the action potential. However, the dihydropyridines (e.g. nifedipine, amlodipine) have relatively little effect on the heart because they have a much higher affinity for channels in the inactivated state. Such channels are more frequently found in vascular smooth muscle because it is relatively more depolarised compared to cardiac myocytes. Furthermore, at clinical doses, vasodilatation results in a reflex increase in sympathetic tone that causes a mild tacchycardia and counteracts the negative inotropic effect. Amlodipine, which has a long duration of action, produces less tachycardia than nifedipine.
How do the non-dihydropyridine CCBs affect cardiac function?
The non-dihydropyridines include diltiazam and verapamil. Verapamil, and to a lesser extent diltiazam, depress the sinus node, causing a mild resting bradycardia. Verapamil binds preferentially to open channels and is less affected by the membrane potential. Conduction in the AVN is slowed and, because the effect of verapamil (unlike nifedipine) is frequency dependent, it effectively slows the ventricular rate in atrial arrhythmias.
The negative inotropic effects of verapamil and diltiazam are partially offset by the reflex increase in adrenergic tone and the decrease in afterload. Diltiazam has actions intermediate to those of verapamil and nifedipine and is popular in the treatment of angina because it does not cause tacchycardia.
What is involved in PCI and when is it used for stable angina?
PCI is performed by passing a fine guidewire across a coronary stenosis under radiographic control and using it to position a balloon which is then inflated to dilate the stenosis. A coronary stent is a piece of coated metallic “scaffholding” that can be deployed on a balloon and used to maximise and maintain dilatation of a stenosed vessel.
PCI is an effective symptomatic treatment for angina but has not been shown to improve survival in patients with stable angina. It is mainly used to treat single or two vessel disease. CABG surgery is usually the preferred option in patients with three vessel of left main disease.
What are the complications of PCI?
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 mortality risk is <0.5%. The main long term complication is restenosis. The routine use of stents in appropriate vessels reduces both acute complications and the incidence of restenosis. Drug eluting stents can reduce the 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 glycoprotein IIb/ IIIa receptor antagonists, improves the outcome of PCI with lower short and long term rates of death and MI.
Which vessels are used for a CABG?
The internal mammary arteries, radial arteries or reversed segments of saphenous veins can be used to bypass coronary artery stenosis, usually under cardiopulmonary bypass.
What are the complications of CABG?
The operative mortality is approximately 1.5% but higher in elderly patients and those with poor LV function or significant co-morbidity (e.g. renal failure). There is a 1-5% risk of post operative stroke.
What is the prognosis following a CABG?
Approximately 90% of patients are angina free 1 year after surgery, but <60% of patients are asymptomatic >5 years after CABG.
Arterial grafts have a much better long term patency rates than veins. Treatment with aspirin or clopidogrel improves graft patency while intensive lipid lowering therapy slows progression of disease in the native coronary vessels and grafts. Persistant smokers are twice as likely to die in the 10 years following surgery compared with those who give up smoking 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.
What are the acute coronary syndromes?
This term encompasses unstable angina and myocardial infarction. Unstable angina refers to new onset or rapidly worsening (crescendo) 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 segment elevation MI (NSTEMI) or full thickness ST elevation MI (STEMI).
Acute coronary syndrome may present de novo or against a background of chronic stable angina. The underlying pathophysiology is usually a fissured atheromatous plaque with adherent thrombus formation.
