5.1 Chest pain

5.2 Acute coronary syndromes

STEMI

Reperfusion

Patients with STEMI who present within 12 hours of symptom onset should have a reperfusion strategy implemented emergently. Reperfusion can be obtained by fibrinolytic therapy, PCI, or rarely, with emergency coronary artery bypass grafting. The choice of reperfusion therapy will depend on time from symptom onset, availability of PCI, delay to fibrinolysis, contraindications to fibrinolysis, location and size of the infarct and the presence or absence of cardiogenic shock.

PCI is the best available treatment if provided promptly. It is generally accepted that a delay of 90 minutes between presentation and balloon inflation is the maximum desirable. If this is not possible, fibrinolysis should be used. For patients presenting very early (symptom duration less than 1 hour), fibrinolytic therapy is highly effective, so the maximum tolerable delay to PCI is 1 hour from presentation. For patients aged less than 75 years with cardiogenic shock, PCI markedly improves outcomes.

Fibrinolytic agents include streptokinase and tissue fibrin-specific agents, such as alteplase and tenectaplase. Available evidence suggests that fibrin-specific agents reduce mortality compared to streptokinase, despite an increased risk of intracranial bleeding. Note that streptokinase should not be given to patients who have been previously exposed to it (more than 5 days ago) due to antibody formation. There is also some evidence that it may be less effective in populations with high levels of exposure to streptococcal skin infections, such as Aboriginal and Torres Strait Islander peoples. Contraindications to fibrinolytic therapy are shown in Table 5.2.3. All patients receiving fibrinolyic therapy should be transferred to a PCI-capable centre for further assessment and treatment. In cases of failed fibrinolyisis or if there is evidence of re-occlusion/re-infarction (e.g. recurrent ST elevation), this transfer should be emergent.

Pre-hospital fibrinolysis should be considered when delay to PCI exceeds 90 minutes and transfer times to a fibrinolysis-capable facility exceed 30 minutes.

The evolution of primary PCI has resulted in some systems identifying STEMI prior to hospital arrival and bypassing the ED, instead taking the patient directly to the catheterization laboratory. Even in these systems, it is important that emergency physicians remain knowledgeable and skilled in the diagnosis and management of STEMI, as a substantial proportion of cases self-present to the ED and pre-hospital diagnosis can sometimes be inaccurate.

P2Y₁₂ receptor inhibitors

Patients undergoing primary PCI for reperfusion for STEMI should receive an antiplatelet agent. The choice of agent will depend on balancing the risk of recurrent ischaemic events and bleeding risk in individual patients. If clopidogrel is used it should be given as a high-dose clopidogrel regimen (600 mg oral bolus and 150 mg daily for 7 days, then 75 mg/day for at least 12 months). Potent oral antiplatelet agents (prasugrel and ticagrelor) are alternatives to clopidogrel for subgroups at high risk of recurrent ischaemic events (e.g. those with diabetes, stent thrombosis, recurrent events on clopidogrel or a high burden of disease on angiography). Prasugrel is contraindicated in patients with prior stroke/transient ischaemic attack. Neither prasugrel or ticagrelor should be used in patients with a previous haemorrhagic stroke or in patients with a moderate-to-severe liver disease. For patients undergoing fibrinolysis, 300 mg clopidogrel is recommended.

Antithrombin therapy

Antithrombin therapy should be used in conjunction with PCI and fibrin-specific fibrinolytic agents. The use of antithrombin therapy with Streptokinase is optional. Low molecular weight heparin (e.g. enoxaparin) or unfractionated heparin can be used. There are data suggesting that enoxaparin may provide benefit over unfractionated heparin and dosing and administration are easier leading to recommendations listing it as the preferred agent. If unfractionated heparin is used it should be administered according to local dosing and monitoring guidelines taking into account whether there is concomitant use of glycoprotein IIb/IIIa inhibitors (GP inhibitors) and whether PCI or fibrinolysis was the reperfusion strategy used.

Bivalirudin (a direct thrombin inhibitor) has shown similar efficacy to the heparins with less bleeding. Its place in the management of ACS is evolving.

Glycoprotein IIb/IIIa inhibitors

The role of GP inhibitors is evolving and data are conflicting and complex. Current recommendations are that the decision to use GP inhibitors is a specialist cardiologist decision and that there is no benefit in initiating it before the catheterization laboratory. An exception is that use before the catheterization laboratory may be considered in high-risk patients undergoing transfer for primary PCI in consultation with the receiving cardiologist. Abciximab is the preferred agent.

Non-STEMI

P2Y₁₂ receptor inhibitors

In addition to aspirin, patients should receive P2Y₁₂ receptor inhibitor agents, e.g. clopidogrel 300 mg loading dose and 75 mg/day. This should be withheld if emergency coronary bypass surgery is planned. There are limited data regarding newer antiplatelet agents (prasugrel and tricagrelor) in non-STEMI. In particular, data regarding prasugrel are limited to patients undergoing PCI. Both these agents have increased bleeding risk compared to clopidogrel. The decision to use them in preference to clopidogrel will require careful balancing of the bleeding risk and the risk of recurrent ischaemic events and is best left to the treating cardiologist.

Antithrombin therapy

Subcutaneous low molecular weight or unfractionated heparin should be given until angiography or for 48–72 hours. The dose of low molecular weight heparin should be reduced if there is renal impairment. The dose of heparin is as above.

Glycoprotein IIb/IIIa inhibitors

Current evidence supports selective use of GP inhibitors. Indications may include ongoing ischaemia despite antiplatelet and antithrombin therapy, diabetes and troponin elevation.

β-Blockers

Initiation of a β-blocker is recommended unless contraindicated.

Invasive management

Patients with NSTEMI should have early coronary angiography (ideally within 48 hours), unless they have severe co-morbidities.

Disposition

Disposition depends on the type of ACS. Patients with STEMI and NSTEMI require admission to hospital for further care. Those with STEMI should be admitted to a monitored bed in a cardiac care unit because of the small but significant risk of life-threatening arrhythmia. It has been the practice also to admit patients with NSTEMI to monitored beds, but this is being challenged on the basis that there are subgroups within this classification at very low risk of adverse events. Patients with ACS without ECG changes or cardiac marker elevations require a period of assessment in the ED/chest pain unit and disposition will depend on the risk identified during that process (see Chapter 5.1).

Complications

Arrhythmias and conduction disturbances (see Chapter 5.4)

Pericarditis (see Chapter 5.6)

Acute left ventricular failure and cardiogenic shock

Most MIs are accompanied by some degree of left ventricular failure, which may range in severity from asymptomatic to pulmonary oedema or cardiogenic shock. Mortality depends in part on the degree of left ventricular failure, with cardiogenic shock having a reported mortality of approximately 80%.

Thromboembolism

Thrombus can form on areas of hypokinetic myocardium due to relative stasis and the prothrombotic effects of local inflammatory changes. It is more common with large anterior infarctions with left ventricular aneurysm formation, where the incidence has been reported to be up to 10%. Echocardiography is used to confirm the presence of thrombus. Systemic anticoagulation is required to prevent embolic complications.

Mechanical defects

Mechanical defects may include:

Prognosis

The prognosis of ACS varies substantially between patients, depending on age, co-morbidities, risk factors, severity of coronary occlusion and myocardial necrosis and the presence of complications. Treatment of ACS should be guided by prognosis: the worse the prognosis, the greater the potential impact of treatment. Prognostic scoring therefore has an important role to play in the management of ACS.

The thrombolysis in myocardial infarction (TIMI) score has been developed and validated as a predictor of adverse outcome (mortality, life-threatening arrhythmia or subsequent myocardial infarction) in ACS. Patients are ascribed a score between zero (lowest risk) and seven (highest risk) by scoring one point for each factor listed in Table 5.2.4. Higher scores are associated with a higher risk of adverse outcome, as shown in Table 5.2.5. The TIMI score is simple to calculate and applicable to a wide range of patients. It can be used to predict which patients will benefit from early invasive management. Patients with a TIMI score of 3 or more appear to benefit from early invasive treatment, whereas those with a TIMI score of 2 or less do not. Patients with a TIMI score of 3 or more with ACS should therefore be considered high risk and receive early coronary angiography.

An alternative to the TIMI score is the Global Registry of Acute Coronary Events (GRACE) score, which uses the components outlined in Table 5.2.6. Each component is weighted to give an estimate of the probability of in-hospital and 6-month death or MI. The weighting process makes the GRACE score a little more difficult to calculate in the clinical setting, but allows for a more precise estimate of prognosis. Both web-based calculators and apps for hand-held devices are readily available.

It is worth noting that ST-segment deviation on the ECG and elevated cardiac markers feature in both the TIMI and GRACE scores and are powerful predictors of adverse events following ACS.

Risk-stratification determines subsequent management of patients with ACS. Although this process is typically undertaken by cardiologists, it is worth emergency physicians understanding the process. If patients have a high risk of subsequent adverse events (e.g. 6-month mortality risk exceeding 3%), then early invasive coronary angiography is often recommended. It should also be considered for patients with unstable symptoms even if their estimated risk is lower. Patients whose symptoms are controlled and have a low risk of adverse events can be offered conservative treatment and cardiac testing for ischaemia, such as exercise treadmill testing. CT coronary angiography is increasingly being offered as an alternative to testing for ischaemia and as a step in the diagnostic pathway between risk stratification and invasive coronary angiography.

Likely developments over the next 5–10 years

5.3 Assessment and management of acute pulmonary oedema

Clinical investigations

Electrocardiogram

An ECG is required, looking for acute ischaemia, especially evidence of ST-elevation myocardial infarction (STEMI), which should be immediately treated with appropriate reperfusion strategies.

Imaging

A chest X-ray will show cardiac size (usually enlarged) and help differentiate APO from airways disease. The chest X-ray findings of pulmonary oedema reflect the changes in fluid distribution. Initially, blood is diverted to the upper lobe veins, which become more prominent than normal. As the oedema worsens, interstitial oedema results in basilar and hilar infiltrates, which are hazy and more confluent than patchy, and interlobular oedema is seen as Kerley B lines. There is loss of vascular delineation. In severe APO, widespread changes representing alveolar oedema appear. There may also be pleural effusions if the interstitial pressure exceeds pleural pressure. Changes associated with the underlying cause can also be seen, e.g. cardiomegaly and pleural effusions in cardiogenic APO. It is important to note that the X-ray changes may not be bilateral and may mimic consolidation from other causes, e.g. pneumonia.

Ultrasound scanning (USS) in the emergency department (ED) can be a useful adjunct to physical examination. During ultrasound of the chest, homogeneous vertical comet tails or B-lines, which originate from the pleural line and continue to the bottom of the screen, characterize pulmonary oedema. These are ultrasound resonance artefacts generated by oedematous interlobular septa and are initially seen in the lung bases but, as oedema worsens, extend upwards to the apices. USS can be used to help differentiate the cause of a patient’s dyspnoea. In acute lung injury or acute respiratory distress syndrome (ARDS), the B-lines are non-homogeneous with areas of sparing. In patients with airways disease, horizontal A-lines may be seen, with an absence of B-lines. The B-lines will resolve as pulmonary oedema improves and may be used to follow response to therapy. Findings of jugular venous distension on ultrasound exam are also consistent with APO. Ultrasound scanning of the heart (echocardiography) may also be useful in determining the cause of the APO (e.g. wall motion abnormalities in acute myocardial infarction, right ventricular strain in pulmonary embolus and acute valvular dysfunction).

Blood tests

Blood tests include haemoglobin, electrolytes, cardiac biomarkers or other cause specific bloods as indicated, e.g. lipase.

Brain or B-type natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP) levels may be useful in distinguishing APO from other causes of acute dyspnoea. BNP is the active part of a hormone (pro-BNP) secreted by ventricular myocytes in response to stretch. Its physiological function is to oppose the effects of the activated renin–angiotensin–aldosterone system. NT-proBNP is the inactive part cleaved from pro-BNP and has a longer plasma half-life than BNP. Its levels are also age dependent meaning ‘rule in’ cut points must be age-qualified. Plasma levels rise during acute heart failure and APO. In the setting of acute dyspnoea, levels of BNP<100 pg/mL (or NT-proBNP<300 pg/mL) make a diagnosis of acute heart failure and APO less likely. Conversely, when the BNP levels are>500 pg/mL (or NT-proBNP>450 pg/mL (age<50),>900 pg/mL (age 50–75) and>1800 pg/mL (age>75)), acute heart failure is more likely. Unfortunately, intermediate levels are difficult to interpret and other diagnoses should be sought prior to making a diagnosis of APO. That said, it has been estimated that by combining the intermediate natriuretic peptide marker levels with historical and exam findings consistent with APO, a diagnostic probability of heart failure is around 75%. Diagnostic accuracy may also be improved by combining USS with NP levels or using predictive modelling. False-positive levels may result from such conditions as pulmonary embolism, sepsis and renal failure, as well as advancing age. Positive levels may also occur in patients with chronic heart failure, but with a different cause of their acute ED presentation of dyspnoea. In addition, false-negative results may occur in the early phases of APO, owing to the delay prior to secretion of natriuretic peptides, as well as in obese patients and those with valvular or pericardial heart disease. These aspects, as well as the relatively high cost of the test, have limited its uptake in EDs in some countries. Currently, its main utility in the Australasian context involves following levels as a guide to therapeutic response, often in chronic heart failure patients. There is potential for using natriuretic peptide level changes within an ED presentation to guide disposition decisions (including discharge of non-APO heart failure patients), but this has not yet been studied prospectively.

Oximetry

Oximetry (in some cases supplemented with arterial blood gases) will reflect severity and help monitor the patient’s response to therapy. Rarely, in more severe cases, invasive monitoring may be useful.

Treatment

In all patients with APO, management strategies should provide supportive care to maximize cardiac output and oxygenation, followed by treatment of the underlying cause.

Treatment of the patient with non-cardiogenic pulmonary oedema consists of removing the patient from the causative environment, supportive therapies aimed at maintaining oxygenation, including non-invasive and invasive ventilation in severe cases, and treating the underlying cause. These patients have lung injury and therefore low volume; low pressure lung protective ventilation regimens should be followed.

Most patients with APO in the ED have a cardiogenic aetiology. Therapy varies according to haemodynamic parameters.

Normotensive or hypertensive patients

The mainstays of treatment are reduction of preload and afterload with nitrates and optimization of oxygenation, often with non-invasive ventilatory support. The patient should be managed sitting up. This posture reduces ventilation–perfusion mismatch and helps with the work of breathing.

Nitrates

Nitrates are the mainstay of pharmacological therapy of APO. They act to increase cyclic guanosine monophosphate (cGMP) in smooth muscle cells, leading to relaxation. In lower doses, this predominantly causes venodilatation and preload reduction. At higher doses, the arterioles are also affected, leading to afterload and blood pressure reduction. In addition, coronary artery dilatation leads to increased coronary blood flow. Myocardial work and oxygen demands are reduced and oxygen delivery is improved. Nitrates are therefore the ideal agents for treating APO by reversing pathophysiological processes that underlie it. Their use is limited by their hypotensive effect and by the tachyphylaxis that occurs with prolonged use. Therefore, they should be titrated against the patient’s haemodynamics and require careful monitoring. Nitrates are contraindicated in those patients who have taken sildenafil or similar agents within the previous 24 hours, owing to profound vasodilatation and hypotension. They should also be used with caution in patients with fixed cardiac output (e.g. those with severe aortic stenosis or hypertrophic obstructive cardiomyopathy). Although nitrates may also be used topically or sublingually, in the patient with APO, the IV route is preferred, as dosing can be titrated to effect and therapy ceased promptly if the patient becomes hypotensive. Topical or sublingual therapy is often used as a temporizing measure until IV access can be secured. The peak effect of IV nitrates occurs after 5 minutes.

The usual dosing regimen is to begin the infusion at 5–10 μg/min and increase the rate by 10–20 μg/min every 3 minutes, titrated to clinical effect and limited by falling blood pressure. If a patient has not responded to nitrate by a dose of 200 μg/min, they are unlikely to respond to further dose increases. Some studies have looked at using higher-dose bolus IV nitrates and have shown good efficacy and safety, with improved results over low-dose nitrates, frusemide and non-invasive ventilation. These studies, however, have limitations of small patient numbers, retrospectivity or non-randomization and these dosing regimens are not currently widely used.

Sodium nitroprusside

Sodium nitroprusside is a potent vasodilator with rapid action on both the venous and arterial systems. It has beneficial actions in APO by reducing both preload and afterload. It can lead to rapid improvements in haemodynamic parameters and cardiac output without the renal complications of other agents. Due to its swift and sometimes profound hypotensive action, invasive blood pressure monitoring is recommended. Rebound vasoconstriction can occur if the drug is stopped abruptly, so it should be slowly weaned. In addition, longer duration of use (>72 hours) has been associated with cyanide toxicity, especially in patients with renal or hepatic disease, in whom it should be used with extreme caution. Nitroprusside is a valid vasodilator alternative to nitrates and can be used when nitrates are contraindicated in non-hypotensive patients.

Angiotensin-converting enzyme inhibitors (ACEIs)

ACEIs have a clear role in the treatment of chronic heart failure. Their use in APO is more controversial. ACEIs effectively reduce afterload and, in cardiogenic pulmonary oedema, can also improve pulmonary capillary wedge pressure and cardiac output. In a small prospective study, when added to standard therapy, they produced a more rapid improvement in haemodynamic parameters and symptoms than placebo. Their use in pulmonary oedema was also associated with reduced intubation rates and ICU length of stay. Unfortunately, there are no large randomized trials looking at the use of ACEIs in APO patients.

ACEIs can also produce prolonged first dose hypotension and can worsen renal function, especially when used in combination with diuretics. Therefore, these agents should be used with caution, especially in patients who have renal impairment or are hypotensive. At present, it is not recommended they be initiated as first-line therapy in APO patients, but should be commenced, with appropriate monitoring of blood pressure and renal function, once the patient has stabilized.

Frusemide

Frusemide has been the first-line treatment for patients with APO for many years. Its usefulness is due to venodilatatory properties that lead to reduced preload, as well as to its diuretic properties. The venodilatation occurs about 15 minutes after IV dosing, well before diuresis begins. Frusemide can, however, lead to increased peripheral vascular resistance via reflex sympathetic and renin–angiotensin system actions. As mentioned above, fluid overload is not usually a contributing factor in acute heart failure and so diuresis is not a necessary endpoint of therapy. The obvious exception is in patients with APO of iatrogenic origin after IV fluid therapy.

Although it is an established therapy, there are no controlled studies that show benefit from the use of frusemide in APO. At least two studies have shown that nitrates are more beneficial than frusemide in relation to haemodynamic and clinical outcomes. High-dose frusemide has been associated with worsening renal function, ICU admissions and poor outcomes in patients with acute heart failure. Nevertheless, a single dose of frusemide at 1–1.5 mg/kg is still commonly recommended in the initial management of this illness.

Morphine

In the past, morphine has been one of the major drugs used in the treatment of APO. It can cause vasodilatation and decreased sympathetic activation; however, it has significant adverse effects including respiratory and central nervous system depression, hypotension and decreased cardiac output. A small prospective study and a number of large retrospective studies have shown an association between morphine use in APO patients and increased rates of intubation, ICU admission and death. As there is no evidence showing benefit from the use of morphine in the treatment of APO and there is an increasing body of literature associating it with harm, morphine should not be used routinely in the treatment of patients with APO. It may be considered for the relief of chest pain that is resistant to nitrate therapy in patients who do not have an altered conscious state, respiratory depression or hypotension. If it is used, it should be in small, titrated IV doses with close observation.

Aspirin

The most common cause of APO in patients presenting to ED is myocardial ischaemia/infarction. Aspirin has been shown to reduce the risk of death and myocardial infarction in patients with myocardial ischaemia. Although it does not directly treat APO, when the cause is thought to be myocardial ischaemia, aspirin should be given.

Ventilatory support

Patients with APO should be given high-flow supplemental oxygen using an oxygen delivery system that can meet their minute volume needs, such as a Venturi system. They are hypoxic and, uncorrected, this will worsen APO through direct pulmonary vascular constriction and reduced myocardial oxygen delivery. Prolonged supranormal oxygenation, however, should be avoided, especially in those patients with underlying airways or other chronic lung disease. In these patients, oxygen should be used judiciously and weaned as soon as the patient is improving, aiming for low normal oxygen saturations.

Patients with a severely reduced level of consciousness, agonal respirations or respiratory arrest require endotracheal intubation and mechanical ventilatory support. This should be accomplished using rapid-sequence intubation.

The introduction of non-invasive ventilation (NIV) using continuous positive airway pressure (CPAP) or bi-level positive airway pressure (Bi-PAP) has allowed many patients to avoid endotracheal intubation. Initial CPAP pressures of 5–10 cm H₂O are used and then titrated to effect. When using Bi-PAP, expiratory pressures are usually begun at 3–5 cm H₂O, with the inspiratory pressure 5–8 cm higher. The benefits of these therapies are due to a number of effects. Oxygen concentration can be accurately controlled and higher percentages can be delivered than via a face-mask. By using CPAP, functional capacity is increased by alveolar recruitment, with a resultant increase in gas exchange area, improved pulmonary compliance and reduced work of breathing. The addition of inspiratory pressure support with Bi-PAP further reduces the work of breathing and may be more useful in hypercapnic or tiring patients. Cardiovascular effects result from positive intrathoracic pressures, with reduced venous return and reduced left ventricular transmural pressures. These preload and afterload effects improve cardiac output without increasing myocardial oxygen demand. In general, these therapies have few complications and are considered safe. Complications that have been reported include nasal bridge abrasions, patient intolerance, gastric distension and aspiration, pneumothorax and air embolism. The last three potentially serious adverse events are extremely rare and appear to occur in selected populations with other underlying disease processes (e.g. pneumothorax in patients with Pneumocystis carinii pneumonia).

A number of studies have compared CPAP and/or Bi-PAP both with each other and with conventional therapy in APO. Most studies have been small and a number of meta-analyses have analysed their combined data. When CPAP was compared to standard medical therapy, there were significant improvements in oxygenation, ventilation, respiratory rate and distress and heart rates, without significant adverse events. There were also significantly reduced rates of endotracheal intubation, intensive care unit length of stay and, more importantly, reduced mortality. There is also a clear reduction in the rate of intubation and ICU admission when using Bi-PAP compared to standard therapy. There also appears to be a trend towards a mortality benefit although, in most analyses, it does not reach significance. Bi-PAP is associated with a more rapid reduction in symptoms than CPAP and may be particularly useful in patients with coexisting airways disease and acute on chronic respiratory acidosis. In the earliest trials of Bi-PAP in APO, there appeared to be an unexplained increase in the rate of myocardial infarction among patients in the Bi-PAP groups. These trials involved very small numbers and had methodological issues. Subsequent trials and meta-analyses have not shown an increase in myocardial infarct rates among the Bi-PAP groups.

When CPAP and Bi-PAP were compared with each other, there was no significant difference in intubation, myocardial infarction or death rates. As there is no convincing evidence of benefit of Bi-PAP over CPAP and no proven mortality benefit of Bi-PAP over standard therapy, CPAP is currently the NIV method of choice in APO, unless the patient has underlying airways disease or significant acute on chronic respiratory acidosis.

New pharmacological agents

Levosimendan comes from a class of drugs known as the calcium sensitizers and is currently only available in Australasia via the special access scheme. It binds to troponin-C and stabilizes the molecule in its pro-contraction state, prolonging contraction. This occurs without impairment of diastolic relaxation and without increasing calcium concentration (with its concomitant risk of arrhythmia and cell death). Cardiac output increases and pulmonary capillary wedge pressures decrease without significantly increased oxygen demand. It also causes vasodilatation (venous and arteriolar) via potassium channel opening, leading to reduced preload and afterload. Adverse effects include tachyarrhythmias, hypotension, hypokalaemia and headache. QTc may also increase. A large randomized trial failed to show a mortality benefit when levosimendan was compared with dobutamine in patients with acute decompensated heart failure requiring inotropic support. Adverse events including hypotension, atrial fibrillation and hypokalaemia were also increased in the levosimendan group. As yet, there are no trials examining its use in patients with acute pulmonary oedema.

Nesiritide is currently available in the USA and some other regions, but not in Australia. It is a recombinant brain natriuretic peptide and acts to cause arterial (including coronary) and venous vasodilation and to suppress the renin–angiotensin–aldosterone and sympathetic nervous systems. Although its mechanism of action would suggest a benefit in patients with APO, a recent large randomized controlled study failed to show any benefit over standard care in symptom control, rehospitalization rate or death and demonstrated problems with hypotension in patients with acute decompensated heart failure. Its use is limited to patients not responding to or with contraindications to other therapies.

Nicorandil is a hybrid vasodilator that causes combined preload and afterload reduction via activated K_ATP channels and a nitrate-like effect. It also has a cardioprotective effect by activating mitochondrial K_ATP channels. When given as a bolus to heart failure patients, it decreases pulmonary capillary wedge pressure and improves cardiac index. It has been associated with decreased in-hospital mortality and readmission rates of patients in acute heart failure. There are no prospective trials and it has not been specifically studied among APO patients.

Adenosine A1 receptor antagonists are a class of drugs that can improve diuresis by inhibiting sodium-induced tubuloglomerular feedback (with resultant fall in renal blood flow and glomerular filtration rate) seen with loop diuretics. Initial studies of the first drug in this class, rolofylline, showed encouraging improvements in dyspnoea without worsening renal function in acute heart failure patients. However, when compared with placebo in a recent large randomized trial, the drug did not show benefits and there were increased adverse events, particularly seizures. It has not been studied in APO patients.

Serelaxin. Relaxin is a hormone released during pregnancy with actions that include nitric oxide production and inhibition of endothelin and angiotensin II. It produces systemic and renal vasodilatation and increased vascular compliance. In the RELAX-AHF trial, serelaxin, a synthetic form of human relaxin, was compared to placebo in addition to standard therapy in patients with acute heart failure. Serelaxin was associated with improved dyspnoea and signs of cardiac failure with less diuretic use, as well as decreased intensive care unit and hospital length of stay. There was no mortality or decreased rehospitalization rate at 60 days. As with all the newer acute heart failure drugs, there is only a small body of evidence concerning this medication and none looking specifically at APO.

Endothelin receptor antagonists. Endothelin is a potent vasoconstrictor and modulator of the sympathetic nervous and renin–angiotensin–aldosterone systems. Tezosentan, an endothelin receptor antagonist, was shown to increase cardiac index, reduce pulmonary capillary wedge and pulmonary arterial pressures and reduce systemic vascular resistance in patients with moderate to severe heart failure. Unfortunately, in large randomized trials (VERITAS 1 and 2), when compared with placebo and added to standard care, it showed no benefit in terms of dyspnoea, worsening heart failure or death.

Hypotensive patients

In general, patients with APO who are hypotensive are at the most severe end of the disease spectrum, defined as cardiogenic shock. They require both ventilatory and haemodynamic support. Endotracheal intubation using rapid-sequence intubation and ventilation maximizes oxygen delivery and minimizes oxygen utilization. A positive end-expiratory pressure of 5–10 cm H₂O may be useful. These patients may have a fluid deficit and, therefore, cautious fluid bolus resuscitation should be titrated against haemodynamic parameters and clinical effect. Inotropic support is also required, with epinephrine (adrenaline) being the first-line agent. Cardiac output may be improved with dobutamine but can it lead to hypotension requiring the concomitant use of vasopressors. These drugs will increase cardiac output, but do so at the expense of increased myocardial oxygen demand and increased arrhythmogenicity. Invasive monitoring will be required in this group as it helps guide fluid and inotropic management. Some time may be bought by the use of invasive therapeutic manoeuvres, such as an intra-aortic balloon pump. This device reduces myocardial oxygen demand via afterload reduction and increases coronary flow through diastolic augmentation. Reversible causes should be treated, e.g. reperfusion for acute myocardial infarction or surgical correction of acute valvular dysfunction.

5.4 Arrhythmias

Essentials

1 Cardiac arrhythmias require urgent attention, as some are life threatening and can lead to sudden death.

2 The most important initial evaluation is for haemodynamic stability. Patients who are haemodynamically stable should have a 12-lead electrocardiogram (ECG), whereas unstable patients require immediate intervention.

3 The patient’s underlying medical condition is very helpful in making a correct diagnosis of the arrhythmia.

4 Bradyarrhythmias should always be evaluated in the light of the patient’s presenting symptoms as well as the ECG abnormality.

5 Patients with wide complex tachycardia should be considered to have ventricular tachycardia unless proved otherwise.

Introduction

Arrhythmia is the term used to describe an abnormal heart rhythm. The most common arrhythmias are atrial or ventricular ectopic beats. Tachycardia occurs when the heart rate is>100 beats per minute (bpm) and bradycardia is defined as a rate of<60 bpm. The management of cardiac arrhythmias depends on the presentation of the patient, haemodynamic stability, underlying heart disease (if any) and the exact type of the arrhythmia. Patients with asymptomatic stable arrhythmias in the absence of underlying heart disease usually do not require emergency treatment. However, patients with symptomatic arrhythmias, especially when associated with underlying heart disease, require more urgent therapy. The key objective in a patient with haemodynamic instability is restoration of adequate cardiac output to maintain cerebral perfusion as well as a stable rhythm, using interventions least likely to cause harm.

Pathophysiology and pathogenesis

An understanding of cardiac arrhythmia requires knowledge of the normal conduction system (Fig. 5.4.1). In the normal heart, electrical impulses start from the sinoatrial (SA) node and conduct via the atria to the atrioventricular (AV) node. The electrical impulses then conduct down the bundle of His to the right and left bundle branches and, subsequently, via the Purkinje fibres to the ventricular myocardium.

Different mechanisms, such as re-entry, enhanced automaticity and triggered activity, can result in arrhythmias. Generally, arrhythmias are thought of as abnormal impulse generation or abnormal impulse conduction. Abnormal impulse generation in the SA node, as in sick sinus syndrome, can result in failure of impulse formation. Abnormal impulse conduction in the AV node can result in failure of electrical conduction from the atrium to the ventricles, resulting in various degrees of AV block. Ectopic impulses in the atria result in atrial ectopics or atrial tachycardia. Accessory pathways between the atrium and ventricle can result in supraventricular tachycardia. Abnormalities in ventricular conduction can result in bundle branch blocks or a variety of intraventricular conduction abnormalities. The most dangerous arrhythmias arise from the ventricles, as these, especially in the presence of underlying structural heart disease, may be associated with sudden death.

Re-entry

Re-entry occurs when a closed loop of conducting tissue transmits an electrical impulse around the loop and stimulates atrial or ventricular electrical activity with each pass around the circuit. Atrial and ventricular fibrillation and flutter are examples of micro re-entry, whereas paroxysmal supraventricular tachycardia is an example of macro re-entry.

Principles of assessment and management

Patients with arrhythmias may present with symptoms due to the arrhythmia or may be asymptomatic and have the arrhythmia noticed during routine examination or investigations. All patients should initially be managed in an area where cardiac and other physiological monitoring is available.

The urgency of treatment is dictated by the patient’s clinical condition. For stable patients, the usual clinical process including history, physical examination and investigations (particularly ECG), is appropriate. For the unstable patient, urgent intervention is required, with restoration of a stable cardiac rhythm and cerebral perfusion being the priority. Clinical information, if promptly available, may be useful. For example, a patient with a history of renal failure or heart failure taking spironolactone should raise the suspicion that a wide complex tachycardia is due to hyperkalaemia.

Intravenous access should be obtained and blood drawn for investigations, such as full blood counts, electrolytes and cardiac markers (if indicated). A 12-lead ECG is essential and a chest X-ray may be helpful. Other specific investigations, such as serum digoxin level, thyroid function tests and theophylline levels, may sometimes be indicated, depending on the arrhythmia and the clinical context.

The management of arrhythmias should begin with attention to the airway, breathing and circulation. Management of cardiac arrest is discussed in Section 1.

Bradyarrhythmias

Bradycardia is defined as a heart rate of less than 60 bpm. It is important to take into account the patient’s underlying clinical state when treating bradyarrhythmias. ECG diagnosis of bradyarrhythmias can be simplified by the algorithm in Figure 5.4.2. Note that denervated transplanted hearts will not respond to atropine and so, if treatment is required, pacing, catecholamine infusion or both should be used.

Sinus bradycardia

Physiological sinus bradycardia may be associated with good physical conditioning (e.g. marathon runners), drug effects (e.g. β-blockers, calcium antagonists) and vagal stimulation (e.g. vomiting). More serious causes include acute inferior myocardial infarction, raised intracranial pressure, hypothermia and hypothyroidism.

Clinical features

There are often no signs or symptoms. Symptoms may be related to the underlying cause.

Clinical investigations

ECG features are:

Treatment

Treat the underlying cause. If there is evidence of hypoperfusion, intravenous atropine 0.4–0.6 mg may be used while the cause is investigated. Physiological bradycardia does not require treatment. Disposition will depend on the cause.

Sick sinus syndrome (bradycardia–tachycardia syndrome)

This is most commonly found in elderly patients and results from fibrosis around the sinus node. It can also occur with congenital heart disease, rheumatic disorders, myocarditis, pericarditis, rheumatological disease, metastatic tumours, surgical damage, cardiomyopathies and ischaemic heart disease. It is a heterogeneous disorder that includes a wide variety of intermittent supraventricular tachycardias and bradyarrhythmias. Pathophysiologically, there is sinus bradycardia with intermittent failure of sinus node function, with the prolonged pause interrupted by a temporary escape rhythm. Drugs, such as β-blockers, digoxin and antiarrhythmics, as well as conditions, such as abdominal pain, thyrotoxicosis and hyperkalaemia, can exacerbate the condition.

Clinical features

Typical features are syncope, light-headedness, palpitations, dyspnoea, chest pain, collapse and cerebrovascular accidents.

Clinical investigations

ECG features are:

Treatment

Unstable patients should be managed with atropine 0.4–0.6 mg IV as a bridge to pacing. If not effective, then consider adrenaline (epinephrine) infusion (2–10 μg/min) or dopamine (2–10 μg/kg/min) infusion if pacing is delayed. Transcutaneous pacing should be required if drugs are ineffective. Drug treatment for tachyarrhythmia risks aggravating pre-existing AV block or sinus arrest and should be avoided until pacemaker insertion. These patients eventually require a permanent pacemaker.

Heart block

First-degree AV block

In first-degree AV block, conduction of the atrial impulse to the ventricle is delayed. A P wave precedes each QRS complex, but the PR interval is more than 0.2 seconds. Causes include drug effects, vagal stimulation, inferior myocardial infarction and high vagal tone (especially in young patients). Rarely, it is a sign of myocarditis (e.g. rheumatic myocarditis), digoxin toxicity, idiopathic fibrosis or aortic valve disease.

There are no specific clinical features.

ECG features (Fig. 5.4.3) are:

Usually, no specific treatment is required. Unless associated with acute ischaemia, first-degree AV block is not itself an indication for hospital admission.

Second-degree AV block: Mobitz type I (Wenckebach)

In Mobitz type I AV block, conduction of the atrial impulses to the ventricles is intermittently blocked. This condition is due to impaired conduction in the AV node and so the atrial rate is greater than the ventricular rate. There is a progressive increase in the PR interval until a dropped QRS complex occurs. After the dropped QRS, AV conduction recovers, resulting in a normal PR interval and then the progressive increase in PR interval starts again. Anatomically, this block is above the bundle of His in the AV node. It is thought to be due to an increased impulse conduction interval at the AV node.

Causes include inferior myocardial infarction, digoxin toxicity and high vagal tone. The condition is nearly always benign and asymptomatic but, in the setting of acute ischaemia, may progress to complete heart block.

There are no specific clinical features.

ECG features (Fig. 5.4.4) are:

No treatment is required for stable patients. Atropine, dopamine/adrenaline infusion or cardiac pacing may be indicated in the haemodynamically unstable patient.

Second-degree Mobitz type ll AV block

Mobitz type II AV block is due to intermittent failure of conduction of atrial impulses to the ventricles. The PR interval remains constant, but there is regular, intermittent failure of P-wave conduction. This is usually due to impaired conduction in the bundle of His or bundle branches (i.e. it is infranodal). Advanced second-degree block is the block of two or more consecutive P waves. This condition may be seen with acute coronary syndrome involving the left coronary artery or, less commonly, idiopathic fissure of the bundle branches.

Although it may be asymptomatic, Mobitz type II AV block is more likely to be associated with stroke, Stoke–Adams attacks (syncope), a slow ventricular rate and sudden death.

ECG features (Fig. 5.4.5) are:

If the patient is haemodynamically unstable, give atropine 0.4–0.6 mg IV. If not effective, consider adrenaline (2–10 μg/min) or dopamine (2–10 μg/kg/min) infusion. Occasionally, pacing may be needed. Patients with this condition should be admitted, as it can deteriorate to complete heart block.

Third-degree (complete) AV block

In third-degree or complete AV block, conduction of the atrial impulse to the ventricles is completely blocked. Subsidiary pacemakers arise. If they are within the bundle of His, QRS complexes are narrow (Fig. 5.4.6). In contrast, if the block is infranodal, subsidiary pacemakers usually arise in the left or right bundle branches and the QRS complexes are wide (Fig. 5.4.7). The commonest cause of complete heart block is myocardial fibrosis. It is also seen in up to 8% of inferior myocardial infarctions, where it is often transient. Complete heart block is also associated with sick sinus syndrome, Mobitz type II block and transient second-degree block with new bundle branch or fascicular block.

The patient may be asymptomatic, however, syncope or near syncope is common. Clinically, cannon ‘a’ waves may be seen in the neck veins and the first heart sound may vary in loudness.

ECG features are:

 complete dissociation of P waves and QRS complexes

 ventricular escape pacemaker is at 20–50 bpm

 QRS may be wide or narrow.

Haemodynamically compromised patients should have measures taken to increase ventricular rate to a level that results in adequate perfusion. Judicious use of atropine 0.4–0.6 mg IV may be helpful. If this is unsuccessful, dopamine or adrenaline infusions, titrated to effect, may be effective. In ischaemic tissue, adrenaline is preferred, as coronary perfusion is better maintained. External pacing may be required if these measures are ineffective. Admission is required and permanent pacing is often necessary.

Never treat third-degree heart block with ventricular escape beats using lignocaine or any agent that suppresses ventricular escape rhythms as this will suppress the already slow heart rate, resulting in reduced cardiac output.

Tachyarrhythmias

There is a wide range of tachyarrhythmias. Immediate diagnosis and management may be considered on the basis of the width of the QRS complex and the regularity of the rhythm (Fig. 5.4.8).

Broad complex tachycardias

The differential diagnosis of a regular broad complex tachycardia includes ventricular tachycardia (VT) or supraventricular tachycardia (SVT) with aberrant conduction. Considerable research has been undertaken in an attempt to define ECG criteria that can reliably distinguish SVT from VT. Although relatively high sensitivities for some criteria have been reported, the high prevalence of VT in emergency department (ED) patients with broad complex tachycardia (approximately 80% in some studies) lowers the predictive value of those criteria. Features that increase the chance of a broad complex tachycardia being VT are shown in Table 5.4.1. It is usually safest to treat a broad complex tachycardia as VT unless there is very strong evidence to the contrary. In the older patient with underlying ischaemic heart disease, syncope and hypotension, VT would be the most likely diagnosis.

Ventricular tachycardias

The proper identification of a ventricular arrhythmia is important in the evaluation of a patient. The management of ventricular arrhythmia depends on the correct identification of the rhythm, assessment of the risk–benefit ratio of antiarrhythmic drug therapy and an awareness of non-pharmacological modes of treatment. The presence or absence of heart disease and left ventricular function (ejection fraction) also influence the management approach. Risk increases with the severity of structural heart disease and left ventricular dysfunction.

Monomorphic ventricular tachycardia

Sustained VT is defined as a succession of ventricular impulses at a rate of>100 per minute and lasting more than 30 seconds or resulting in haemodynamic compromise. If the patient is haemodynamically stable, a 12-lead ECG should be recorded to characterize morphology.

Patients may be asymptomatic or complain of palpitations, dizziness or chest pain. Cannon ‘a’ waves may be seen in the neck veins. The patient may lose consciousness.

ECG features (Figs 5.4.9 and 5.4.10) are:

 AV dissociation

 fusion beats or capture beats

 wide QRS complexes>140 ms

 rate>100 bpm: commonly 150–200 bpm

 rhythm regular, although there is some beat-to-beat variability

 constant QRS axis, often with marked left axis deviation or northwest axis

 deep S wave with r/S ratio<1 in right bundle branch block (RBBB) morphology VT.

AV dissociation, captured beats or fusion beats, if present, are pathognomonic of VT. However, they are rarely seen because the rate of VT must be slow, usually<120 bpm for it to be easily visible.

Treatment

VT should be managed according to current AHA/ACC guidelines. Management of pulseless VT is addressed in Section 1 of this book. All patients with VT require oxygen therapy and IV access, at which time blood for electrolyte and cardiac marker analysis is obtained. Electrolyte imbalances, particularly of potassium, should be corrected.

An unstable patient requires emergency cardioversion, with sedation as required. Caution is needed, especially as these patients usually have low blood pressure. The first recommended DC shock should be 100 J (synchronized). If this does not convert the rhythm, it can be increased to 150 J and then 200 J. This can be further increased to 360 J if required. The equivalent biphasic energy should be used for biphasic defibrillators (e.g. escalating 70 J, 120 J, 150 J, 170 J). Shock-resistant VT may respond after administration of amiodarone. Lignocaine, magnesium and procainamide are considered second-line adjuncts to cardioversion as there is less evidence to support their efficacy. Nifekalant can also be considered, where available. An infusion of either amiodarone or lignocaine should be commenced after cardioversion. If the blood pressure is low, consider the use of inotropic support, for example dopamine infusion.

Stable patients may be treated with:

 intravenous amiodarone 150 mg as a slow bolus over 10 minutes. This can be repeated a second time if conversion has not been achieved

 an alternative is IV procainamide 100 mg (where available) every 5 minutes to a maximum dose of 10–20 mg/kg body weight

 intravenous lignocaine 50–100 mg IV push at a rate not more than 50 mg/min. This can be repeated a second time if conversion is not achieved. It should be noted, however, that lignocaine is relatively ineffective for terminating haemodynamically stable VT of unknown aetiology.

Sotolol 1 mg/kg is used as second-line agent. Following successful conversion, an infusion of the successful agent should be commenced for maintenance therapy. If pharmacological therapy is unsuccessful, cardioversion under sedation is indicated.

Polymorphic VT

VT with a continuously varying QRS morphology is called polymorphic VT. It is often associated with ischaemia and tends to be more electrically unstable than monomorphic VT.

Polymorphic VT includes a specific variant called torsades de pointes, which is associated with a prolonged QT. This is characterized by QRS peaks that twist around the baseline (Fig. 5.4.11) and this occurs in the presence of repolarization abnormalities. Causes are summarized in Table 5.4.2.

Syncope is the usual presenting symptom.

ECG features include:

Torsades de pointes may be sensitive to magnesium. A bolus of 2 g over 1–2 minutes followed by an infusion will usually cause reversion. Cardioversion is recommended if the patient is haemodynamically compromised, but torsades de pointes can be resistant. Accelerating the heart rate, thereby shortening ventricular repolarization (e.g. by overdrive pacing to a rate of 90–120 bpm or isoprenaline infusion titrated to similar effect) may be successful. Treatment of the underlying cause is essential as torsades de pointes is very difficult to control. Beta-blockers can also be considered for congenital prolonged QT syndrome.

Idiopathic ventricular tachycardia

Idiopathic ventricular tachycardia is a monomorphic VT that occurs in the absence of structural heart disease. It is often exercise dependent and is named according to its site of origin. The QRS morphology during tachycardia can indicate the site of origin.

Idiopathic ventricular tachycardia presents as one of two subclasses:

Right ventricular outflow tract ventricular tachycardia

Right ventricular outflow tract ventricular tachycardia has a typical LBBB inferior axis morphology. The aetiology is believed to be cyclic-AMP (cAMP)-mediated triggered activity.

It typically occurs in young patients and is slightly more common in females. There is usually no evidence of underlying structural heart disease.

ECG features are:

It is usually responsive to β-blockers as it is catecholamine sensitive. It is important to exclude underlying structural heart disease, especially arrhythmogenic right ventricular cardiomyopathy.

Idiopathic left ventricular tachycardia (ILVT)

Idiopathic left ventricular tachycardia is a fascicular ventricular tachycardia. The pathophysiology is a re-entrant phenomenon in the posterior fascicle of the left bundle branch.

It occurs in young patients without structural heart disease.

On ECG (Fig. 5.4.12), QRS morphology is broad and shows a right bundle branch block pattern with left axis deviation. The duration of the QRS complex is 100–140 ms with an RS interval<80 ms. For ischaemic VT the duration of the QRS complex is usually>140 ms and the RS interval>100 ms. ECG may also show capture beats or fusion beats.

The drug of choice is intravenous verapamil. Amiodarone and sotalol have been reported to be equally effective. Vagal manoeuvres and intravenous adenosine are ineffective in converting this arrhythmia. Lignocaine is not effective for ILVT.

Pre-excited atrial fibrillation

Pre-excited atrial fibrillation (Wolff–Parkinson–White (WPW) AF) is a differential diagnosis for an irregular, wide complex tachycardia.

The patient is usually young (age<50 years) with a previous history of palpitations, rapid heart rate, syncope or documented history of WPW.

ECG features (Fig. 5.4.13) are:

During sinus rhythm, the ECG of patients with WPW shows a PR interval<0.12 seconds, a slurred R-wave upstroke (δ wave) and a wide QRS>0.10 seconds (Fig. 5.4.14).

It is important to distinguish WPW AF from other wide complex tachyacardias. Certain subtypes of polymorphic VT, such as torsades de pointes, present with an undulating baseline. In contrast, WPW AF usually has a stable electrocardiographic baseline with no alteration in the polarity of the QRS complexes.

AF with aberrant conduction occurs when a patient with a pre-existing bundle branch block (or a rate-responsive bundle branch block) has a rapid ventricular response to AF. The ECG will show a wide complex tachycardia of irregular rate with stable beat-to-beat QRS configuration, contrasting with the variable beat-to-beat QRS configuration in WPW AF.

Haemodynamically unstable pre-excited AF is managed by immediate synchronized cardioversion. Haemodynamically stable pre-excited AF could be treated with:

 IV procainamide (30 mg/min, maximum dose 17 mg/kg). Because of the potential for severe hypotension with rapid IV administration, procainamide requires a slow rate of infusion. It may not reach therapeutic blood levels for 40–60 minutes.

 IV ibutilide, a class III antiarrhythmic agent, can also be used. Dosage is 1 mg (0.01 mg/kg for patients<60 kg) over 10 minutes, repeated once after 10 minutes if needed. It has a short half-life of 4 hours. Its dosing does not require adjustment for hepatic or renal function and it is safe in elderly patients. It acts rapidly, with a mean conversion time of approximately 20 minutes

 IV flecainide has been described as an alternative treatment.

Amiodarone administration modifies sinus and AV node properties with little, if any, effect on fast-channel tissues (i.e. accessory pathways) and it is not effective in treatment of WPW with AF.

Narrow complex tachycardias

Sinus tachycardia

Sinus tachycardia is defined as a heart rate>100 bpm. It not an arrhythmia per se, but rather an indication of an underlying disorder. Common causes include shock, hypoxia, cardiac failure, anaemia, drug effects, fever/infection, pain, anxiety, thyrotoxicosis and pregnancy.

Patients may complain of palpitations, but are often asymptomatic. Clinical features would be those of the underlying cause.

ECG features are:

Management is focused on treatment of the underlying cause.

Paroxysmal supraventricular tachycardia

Paroxysmal supraventricular tachycardia (PSVT) originates from either an ectopic atrial focus or a re-entry circuit. Those caused by atrial flutter and fibrillation will be considered separately below.

Re-entry circuits are responsible for pre-excitation, which exists when the whole or part of the ventricular muscle is activated earlier than anticipated. The majority of re-entry circuits involve the AV node. Retrograde conduction may also involve an AV bypass tract. WPW syndrome is the most common of these. It is characterized by an electrically conductive muscle bridge (bundle of Kent) connecting atria and ventricle and bypassing the AV node. ECG when in sinus rhythm may show a PR interval of less than 0.12 s, a δ wave (slurred upstroke) and a wide QRS>0.10 s (see Fig. 5.4.14).

Patients may have palpitations, chest pain or syncope.

ECG features (Fig. 5.4.15) are:

If the patient is haemodynamically unstable, cardioversion is indicated. Sedation is usually required. If the patient is mildly symptomatic but blood pressure is>100 mmHg, vagal manoeuvres may be tried. If vagal manoeuvres are unsuccessful or inappropriate, the choice of drug therapy lies between adenosine (escalating 6 mg, 12 mg and 18 mg rapid boluses into a large vein) or verapamil (continuous slow infusion of 1 mg/min to a maximum of 20 mg or 5 mg IV slowly, which may be repeated). Diltiazem infusion (2 mg/min to a maximum of 50 mg) is an alternative. There is scant evidence to show one approach is more effective than the other. Both have adverse effects. With adenosine, patients experience a transient sense of impending doom, chest discomfort and shortness of breath that can be very distressing. With verapamil, hypotension may occur, hence the cautious administration. Concurrent use of β-blockers may potentiate this. Flecainide (2 mg/kg over 30–45 minutes) would be considered third-line therapy. Patients who are resistant to chemical cardioversion may require electrical cardioversion.

Atrial flutter

Atrial flutter rarely occurs in the absence of underlying heart disease. Causes include ischaemic heart disease, acute myocardial infarction, congestive cardiac failure, pulmonary embolism, myocarditis, chest trauma and digoxin toxicity.

Patients may have palpitations and chest pain or more commonly are asymptomatic.

ECG features (Fig. 5.4.16) are:

Treatment of the underlying illness is essential and will often result in spontaneous reversion. Haemodynamically unstable patients will usually respond to low-energy cardioversion (e.g. 50 J). Flecainide can be used for chemical reversion and verapamil for rate control, if required.

Atrial fibrillation

AF is the result of chaotic atrial depolarization from multiple areas of re-entry within the atria. Thus, there is a lack of coordinated atrial activity. AF is characterized by an irregularly irregular rhythm without discrete P waves and may be acute or chronic. Causes of AF seen in the ED are summarized in Table 5.4.3.

There are three variations of AF:

Clinical features

Patients with acute episodes of AF often experience palpitations, dyspnoea, dizziness or angina. Those with chronic AF often have no specific symptoms, especially if their heart rate is<100 bpm. Clinically, the pulse is irregularly irregular and S1 varies in intensity.

Clinical investigations

Investigations will be guided by the clinical context. Patients with acute-onset AF should have electrolyte studies and thyroid function tests as well as consideration of cardiac marker levels in appropriate clinical contexts. All patients with AF should have echocardiography, if not recently performed. This can be done as an outpatient procedure for those successfully treated in the ED.

ECG features (Fig. 5.4.17) are:

Treatment

Emergency management depends on the chronicity of the condition, the ventricular response rate, haemodynamic stability, the presence of underling structural heart disease and any associated conditions.

The aim of treatment for patients with chronic AF is rate control and treatment of any associated illness. In patients with acute-onset AF, the choice lies between cardioversion in the ED (electrical or pharmacological), rate control and anticoagulation with delayed elective electrical cardioversion or rate control alone. The choice will be governed by the duration of the episode, the age of the patient, known structural heart disease, co-morbidities and previous attempts at cardioversion. There is no evidence that a rhythm control strategy is superior to a rate control strategy. That said, a rhythm-control strategy may be preferred for younger patients, those who are symptomatic, those presenting for the first time with lone AF and those with AF secondary to a treatable/correctable precipitant. A rate-control strategy may be preferred for patients aged over 65, those with coronary artery disease, those with contraindications to antiarrhythmic drugs, those unsuitable for cardioversion and those with congestive heart failure.

Treatment of AF in the ED is summarized in Figure 5.4.18. Haemodynamically stable patients where onset of AF is within 48 hours may be treated with either pharmacological or electrical cardioversion. Where AF is of a longer duration, a delayed elective cardioversion or rate-control-only strategy is indicated. There is a case in otherwise well patients with very recent-onset paroxysmal AF in the absence of structural heart disease or other underlying condition for a period of observation as up to 90% will revert spontaneously – usually within 24 hours.

For pharmacological cardioversion in patients without structural heart disease, a class Ic agent, such as flecainide (2 mg/kg over 20–30 minutes) or propafenone, is recommended. Where structural heart disease is present, amiodarone (2–3 mg/kg over 5–10 minutes, repeated if necessary) is the drug of choice. Ibutilide, dofetilide, quinidine or procainamide (where available) may also be useful for cardioversion.

Rate control can be achieved with β-blockers (e.g. metoprolol 2.5–5 mg IV over 2 minutes, repeated if necessary to a maximum of 15 mg), verapamil (5–10 mg IV over 2–5 minutes), amiodarone or diltiazem.

In patients with life-threatening haemodynamic instability, emergency electrical cardioversion should be attempted, irrespective of the duration of the AF. In patients with WPW syndrome, flecainide may be used as an alternative to attempt pharmacological cardioversion. Atrioventricular node-blocking agents (such as diltiazem, verapamil or digoxin) should not be used.

In patients with known permanent AF where haemodynamic instability is caused mainly by a poorly controlled ventricular rate, a pharmacological rate-control strategy should be used. Beta-blockers or rate-limiting calcium antagonists are the agents of choice or, where these are contraindicated or ineffective, amiodarone should be used.

Multifocal atrial tachycardia

This rare arrhythmia is characterized by three or more atrial foci, a ventricular rate of more than 100 bpm and variable PP, PR and RR intervals. It is associated with chronic obstructive lung disease, hypoxia, electrolyte disturbance, pulmonary embolus and digoxin toxicity. Treatment is directed at improving the underlying condition. Specific treatment of the arrhythmia is rarely required and often not helpful.

Unifascicular blocks

A unifascicular block is a conduction block that affects one of the major infranodal conduction pathways: right bundle branch block (RBBB), left anterior fascicular block (LAFB) or left posterior fascicular block (LPFB). Conduction blocks can be caused by ischaemia, cardiomyopathies, valvular disease, myocarditis, surgery, congenital disease and degenerative diseases (Lenegre or Lev disease).

Left anterior fascicular block

There are no specific clinical features.

ECG features are:

 left axis deviation

 normal QRS duration.

Usually no treatment needed. Treat the underlying cause.

Left posterior fascicular block

There are no specific clinical features.

ECG features are:

 right axis deviation

 normal QRS duration.

Usually no treatment needed. Treat the underlying cause.

Right bundle branch block

RBBB can be a normal variant. Other causes include pulmonary embolism, right ventricular hypertrophy, ischaemic heart disease, congenital heart disease and cor pulmonale.

Clinical features will be those of the underlying cause.

ECG features (Fig. 5.4.19) are:

 rSR pattern, most noted in V1 and V2

 broad S wave in left ventricular leads

 QRS>120 ms in complete RBBB and≤120 ms with incomplete RBBB.

Treatment is of the underlying cause. If there is a new RBBB, the cause should be actively determined.

Left bundle branch block

LBBB is usually pathological. Causes include myocardial infarction, ischaemic heart disease, left ventricular hypertrophy, congenital heart disease and left ventricular strain.

Clinical features will be those of the underlying cause.

ECG features (Fig. 5.4.20) are:

 RR pattern, best seen in left ventricular leads V5 and V6

 QRS>120 ms.

Treatment is of the underlying cause. If there is a new LBBB in the setting of myocardial ischaemia, management should be as for acute myocardial infarction.

Combination blocks

A bifascicular block is a conduction block that affects two of the major infranodal conduction pathways. This may be an LBBB or a combination of RBBB and LAFB or LPFB. Trifascicular block is a combination of conduction blocks of all three fascicles. Examples include:

 RBBB and LAFB with first-degree AV block

 RBBB and LPFB with first-degree AV block

 LBBB with first-degree AV block

 alternating RBBB and LBBB.

Blocks may be permanent or transient. In the setting of an acute myocardial infarction, both bi- and trifascicular blocks may degenerate to complete heart block. Thus admission to a monitored bed is needed and pacemaker insertion considered.

Other disturbances of cardiac rhythm and conduction

Atrial ectopics

Atrial ectopics are mostly asymptomatic and may be precipitated by alcohol, nicotine and caffeine. They may be associated with AF, underlying heart disease or respiratory disease.

ECG features are:

Usually no treatment is necessary.

Junctional rhythm

A junctional rhythm is usually asymptomatic.

ECG features are:

Usually no treatment needed.

Brugada syndrome

The Brugada syndrome is a syndrome with the ECG showing right bundle branch morphology and coved ST segment elevation in V1 and V2 with terminal T inversion (Fig. 5.4.21). The ECG pattern may be associated with sudden cardiac death from ventricular fibrillation. There may be a family history of sudden death. Occasionally, the ECG pattern is seen only during fever or after taking antiarrhythmic drugs, especially class Ic antiarrhythmics, such as flecainide or propafenone. Patients with the Brugada pattern should be referred for further evaluation and risk stratification.

5.5 Pulmonary embolism

Introduction

Pulmonary embolus (PE) is the third most common cardiovascular disease. Historical data suggest that, left untreated, it has high mortality. Treating PE with anticoagulation reduces the overall in-hospital mortality to 4–12%. Of these, most (4–9%) are due to co-morbidity and 1.5–5% directly to PE.

The diagnosis and management of PE is often difficult. It requires careful clinical assessment and methodical application of aids to diagnosis. It relies on the estimation of probabilities rather than any truly definitive test. At all times, the possibility of alternative serious conditions causing the clinical presentation should be considered. All patients being considered for any diagnostic test for PE (including D-dimer assay) should have a documented risk assessment to ensure that use of those tests is safe and appropriate (see diagnostic risk assessment below). In general, if the risk of PE is below 5% (e.g. most low-risk emergency patients), then an alternative diagnosis should be sought first and investigation for PE pursued only if no alternative disease can be found. Indeed, in this population, excessive aggressive radiological investigation may find more false-positive venous thromboembolism (VTE) than real PE or deep venous thrombosis (DVT). The threshold for diagnosis is around 70–80% probability of PE, at which point the benefits of treatment outweigh the risks of non-treatment. These probabilities may vary in individuals if the risks of PE are high (e.g. pre-existing severe lung/heart disease) or bleeding risks are excessive (e.g. high risk of falls, recent major non-compressible bleeding).

Most institutions now use computed tomographic pulmonary angiography (CTPA) and/or ventilation/perfusion (V/Q) scan where definitive diagnosis is necessary. Most diagnostic pathways also include an initial D-dimer assay and venous ultrasound (or CT venography) in cases where there is clinical doubt after imaging. Some centres may also use echocardiography for risk stratification after diagnosing PE and, if available, it should be used for unstable cases. Magnetic resonance imaging (MRI) has been investigated in some centres but is not routinely used (Fig. 5.5.1).

Investigations

The initial screening tests for PE are discussed below.

Chest X-ray

A normal chest X-ray (CXR) in the presence of significant hypoxia is suggestive of PE. However, the CXR is reportedly abnormal in 80–90% of patients diagnosed with PE. If definitely present, an enlarged descending pulmonary artery, pulmonary oligaemia or cut-off, a plump pulmonary artery and ‘Hampton’s hump’ (a semicircular opacity with the base abutting the pleural surface) are all quite specific for PE (70–90%). However, these signs may be subtle (e.g. often identified in retrospect) and have poor sensitivity. Pleural effusion, plate atelectasis, enlarged heart shadow and non-specific consolidation are seen commonly but do not occur more often in PE patients than in other diagnoses. The main role of CXR is the identification of alternative diagnoses. It also assists in deciding which radiological test is best to use between non-SPECT V/Q and computed tomography pulmonary angiogram (CTPA).

ECG

At least 21 potential features on ECG have been postulated as suggesting PE, but they are insensitive and most lack specificity. The most significant are tachycardias (particularly atrial), right bundle branch block (including incomplete or transient patterns), right axis deviation (particularly S1–3), T-wave inversion (especially deep V1–3) and the S1-Q3-T3 pattern. The more features that are present on the ECG, the more suggestive it is for right ventricular strain. These changes have been associated with poorer outcome in PE, particularly the rare S1-Q3-T3 pattern.

Arterial blood gas analysis (ABG)

In recent years, the role of ABG in PE has been challenged. A PaO₂<80 mmHg without other cause makes PE much more likely, however, 12% of patients with PE have PaO₂>80 mmHg. An abnormal A–a gradient marginally increases PE risk, but 20% of patients with PE have normal A–a gradients. In most patients, oximetry is sufficient to exclude significant hypoxaemia (<92%) and little is gained from routine ABG.

D-dimer tests

D-dimer tests have been available since the 1980s. They are well validated in emergency practice and recommended by current guidelines. They have only been shown to have reasonable specificity when used in ED populations.

The D-dimer test is sensitive but non-specific. Positive results occur with many other conditions. Their main role is to reduce the need for further investigations in a significant number of patients (20–60%). By identifying many low-risk patients who do not undergo further investigation, they increase the PE yield in the remaining investigated patients to over 5%, making further investigation of these patients worthwhile. D-dimers are only useful when negative, allowing PE to be excluded in low/intermediate-risk patients.

To be used safely and efficiently, it is important that the following steps are used:

 They should be used as part of a documented diagnostic process.

 Patients must be adequately stratified into either dichotomous low/high- or low/intermediate/high-risk groups, preferably using a validated scoring system. The test is only useful in low or low/intermediate risk-populations, depending on the test being used (see below).

 Patients with little chance of a negative D-dimer should not undergo this test (e.g. recent major surgery, advanced cancer or the shocked patient).

 Patients with prolonged symptoms (over a week) are much more likely to have false-negative tests and should not be tested.

 Other groups with low specificity (e.g. pregnant or older patients, etc.) should have a D-dimer if the avoidance of radiological imaging is deemed important enough to accept the delay for what will likely be a positive result.

 The test should not be used if PE is not a realistic part of the differential diagnosis.

Knowledge of the diagnostic performance of the D-dimer test being used is required to guide test application and interpretation. If a high-sensitivity test, such as VIDAS or one of the newer validated rapid latex tests, is available it is safe to use in low- and intermediate-ED risk groups (<30% chance of PE). Low-sensitivity tests, such as Simpli-Red or most latex agglutination tests, are only appropriate for use in low-risk patients (<10% chance of PE).

Further investigation

If the D-dimer is positive and no alternative diagnosis has become clear, further investigation is indicated. Following screening tests, more definitive investigations, including CTPA or V/Q scan, in some cases supplemented by ultrasound (US) or CT venography, should be performed. V/Q or CTPA are the usual initial investigations. If both are available, the choice is driven by patient-related issues (discussed below with each modality) and local logistics. Pulmonary angiography (PA) is now rarely available as most radiology departments have replaced it with multislice scanners. In unstable patients, echocardiography is the preferred initial test, looking for severe right ventricular dilatation and overload. MRI scanning may be used occasionally for patients where V/Q and CTPA are contraindicated or unavailable.

Computed tomographic pulmonary angiography and venography (CTPA and CTV)

Multislice (16–128) CTPA is available in most centres and after-hours availability is generally better than V/Q scanning. CTPA is preferable to V/Q scan in most patients with pre-existing lung disease because of the likelihood of intermediate probability V/Q scans in these patients. CTPA appears accurate in diagnosing main, lobar and most segmental vessel emboli. Sensitivity for subsegmental emboli is low, but the prevalence (reported to be 6–30%) and clinical significance of these PE is not clear. CTPA with 32–256 slices increases sensitivity for smaller PE, reported as over 90% in some studies and with good specificity (93–99%). However, the PIOPED2 study suggested sensitivity as low as 85% for PE, although when combined with CT venography (CTV), sensitivity improved to 90%. Large numbers of patients have been followed up after a negative CTPA, plus leg imaging if appropriate, with recurrent PE/death only seen in 1–2% and 0.2–0.5% respectively. This prognostic performance is similar to that reported for negative PA or normal V/Q scans.

Many centres now use CTPA alone to exclude significant PE. This is probably a safe strategy in all but high-risk patients without an alternative diagnosis. High-risk patients with negative CTPA should have leg imaging to exclude an embolic source (Fig. 5.5.2).

A major proposed advantage of CTPA is that other thoracic causes of chest pain may be identified. In some series, abnormal findings are seen in up to 60% of scans, with acute serious conditions in 20–30%. However, it is important to note that many of these findings may be incidental but then lead to prolonged further work-ups and additional radiation. Additionally, as scanners become quicker, data on right ventricular size, shape and function may help PE risk stratification.

In some centres, CTV, using the dye run-off from CTPA, images the venous system (legs to heart) instead of separate ultrasound testing. Almost all the additional yield (3–5% additional PE/DVT diagnosed in some studies) is from leg veins. Radiation doses to gonadal areas from pelvic/abdominal scanning should be avoided.

CTPA has some significant problems in clinical practice. In some studies, up to 15% of scans are technically inadequate. It requires significant dye loads, so is unsuitable for patients with renal dysfunction or contrast/iodine allergies. The radiation dose is high. In males, scans are generally to radio-insensitive tissues but, in women with proliferative breast tissues, high radiation doses (2–4 Gy per breast) confer significant increased lifetime breast cancer risk. V/Q scanning and US of the legs should be preferred in all young (including pregnant) female patients. The dose of radiation to the fetus is minimal in both CTPA and V/Q scanning if proper precautions are taken.

Ventilation–perfusion scan (V/Q scan)

V/Q scanning is usually readily available, has a low complication rate, moderate radiation exposure and can be used in patients with renal dysfunction and dye allergies. Problems are that potentially unwell patients may spend a long time in often distant nuclear medicine departments and many centres do not provide 24/7 scanning. Additionally, critics complain that the majority of V/Q scans are non-diagnostic (>50% in the PIOPED study if not risk stratified), requiring additional testing to rule PE in or out adequately. Because patients with obvious CXR abnormalities (e.g. major collapse, pleural effusions, etc.) or major lung disease almost always have indeterminate V/Q scans, they should have CTPA if available.

Two major studies (PIOPED and McMaster) have defined the probabilities of various V/Q scan results and their combination with clinical risk assessment. In most hospitals, scans were defined as normal, low, intermediate or high probability according to the number±size of unperfused lung segments, matched against ventilation. Further management depends on combining clinical risk and V/Q results as discussed below:

 Normal/near-normal scan (14% of scans in PIOPED). This result excludes significant PE. In ED patients and if abnormal CXR is excluded, it is likely that more than 14% of scans will fall into this group.

 High probability (13% in PIOPED). A high-probability scan had a greater than 85% chance of PE. However, this means 15% of patients treated on the basis of a high-probability scan alone would be anticoagulated unnecessarily. The majority of the false positives in this group will be those who had a low pre-test probability. Therefore, patients assessed clinically as low risk with a high probability V/Q scan should have further investigations.

 Low/intermediate (42%/36% in PIOPED). The low- and intermediate-probability groups had around 10–15% and 35% chance, respectively, of PE. Patients with a low clinical risk assessment and a low-probability V/Q have<5% chance of PE. Most of these patients can be discharged if other major diagnoses are excluded. However, consideration of further imaging should occur in patients with critical cardiorespiratory problems, as they have high mortality from even small PE.

Much debate continues on how to manage patients with low clinical pre-test probability and intermediate V/Q. In PIOPED, this combination had rates of PE of 16%. However, studies have shown that with serial, or even single negative lower limb studies excluding DVT, recurrent PE or death rates are acceptably low. Patients with dichotomous risk versus V/Q results (low vs high) or intermediate/intermediate results need further alternative investigation with CTPA and/or leg vein imaging.

V/Q single-photon emission computed tomography (V/Q SPECT)

V/Q SPECT is a new technique combining V/Q scanning with computed tomographic scanning (circular arrays) allowing three-dimensional imaging of the lungs. This improves the clarity of images, gives better anatomical delineation of perfusion defects against known vascular domains and can be combined with low dose CT to look at patients with abnormal CXR or known abnormalities. This allows those units that have familiarity with this technique to give a definitive diagnosis or exclusion of PE in 95% of cases.

There is good evidence that V/Q SPECT gives better information and results than planar V/Q. On this basis, it would be an acceptable alternative to CTPA. Small numbers of outcomes studies suggest that there is good negative predictive value. To date, direct comparisons with CTPA have been limited so the true performance between the two tests is still unclear. Early evidence suggests that V/Q SPECT is probably slightly more sensitive but less specific. The specificity issues are probably reduced by combining V/Q SPECT with a low dose thorax CT to look for lung abnormalities that may explain poor perfusion, particularly in those with known lung disease or with abnormal CXR. Caution should be applied when the result is not concordant with the clinical picture (e.g. low-risk patient with multiple perfusion defects, etc.) and cross-over examinations to a CTPA/US may be advisable. The same is true for single subsegmental perfusion defects. V/Q SPECT is the preferred technique where CTPA is relatively contraindicated or where inadequate CTPA studies have occurred (10–25%). Further studies directly comparing V/Q SPECT with CTPA are awaited.

Magnetic resonance imaging

Magnetic resonance imaging (MRI) techniques are improving rapidly. Although sensitivity for central emboli is>90% with high specificity, its diagnostic performance is much poorer even for PE in large segmental vessels. There is little place currently for MRI in the acute setting unless CT/VQ are unavailable/contraindicated.

Echocardiography – transthoracic or transoesophageal (TTE/TOE)

Echocardiography is a rapid, accurate method of diagnosing massive PE in patients with instability. It helps exclude other causes of hypotension and raised venous pressure, such as cardiac tamponade and major valve or myocardial dysfunction. In massive PE, it can demonstrate right heart distension/dysfunction and sometimes central pulmonary artery or atrial clot. Importantly, it can be performed in resuscitation areas and used to see if initiation of thrombolytic treatment for unstable patients is indicated. It is insensitive for peripheral emboli and is not used to diagnose non-massive PE. However, in haemodynamically stable patients, echocardiography provides prognostic information. If right heart strain is seen, there is a much higher risk of poor outcomes (5–15% vs 0–2% mortality). If available, this information assists management decision making after diagnosis of PE.

Pulmonary angiography

Pulmonary angiography has been the ‘gold standard’ in diagnosing PE with very good sensitivity (98%) and specificity (97–100%) in all but the smallest PE. Because of significant technical, logistical and clinical difficulties and a 0.3% mortality and 3% complication rate, it is now rarely used.

Further investigation of isolated sub-segmental clots

Whenever isolated subsegmental clots are reported on imaging, further tests to exclude false positives are recommended. These include:

 leg imaging if not already performed

 an alternative imaging test to confirm the original result if available/feasible

 senior (treating consultant) review and case-by-case decisions, including the patient’s wishes/preferences, on benefits of treatment vs risk of bleeding.

It is important to remember that false positives are common in patients with these isolated small subsegmental findings no matter what imaging is used.

Treatment

Risk stratification

Patients diagnosed with PE should be risk stratified for short-term/in-hospital prognosis. There are significant differences in both ongoing therapeutic options and the monitoring required for PE patients with different prognoses. Features that determine prognosis are overt haemodynamic instability (including syncope) or prolonged respiratory failure, investigations suggesting right ventricular overload/strain or severe V/Q mismatch and severe underlying co-morbidities.

Haemodynamic or respiratory instability should be clinically obvious, although the use of venous/arterial gases to expose unexpected lactic acidosis/hypoxia, if there is clinical concern, is reasonable. In patients without obvious instability, prognosis may be determined by considering:

Other features that raise concerns for patients are a demonstration of a massive clot load (e.g. massive DVT, centrally located emboli), recurrent PE on adequate therapy and serious cardiopulmonary co-morbidity.

Prognostic scores

Combinations of various clinical features and/or investigations have been studied to try to define low-risk groups for possible early or immediate discharge. The two major systems are the PESI (http://www.mdcalc.com/pulmonary-embolism-severity-index-pesi/) and Geneva prognostic scores, both of which have been prospectively validated. The PESI score was also validated in a large randomized trial confirming safety in selecting patients with PE for home therapy.

General measures

Almost all patients with diagnosed PE need to have a combination of supportive care, including oxygen therapy, thromboprophylaxis, analgesia and careful observation for an initial period while early prognosis is determined and heparin or fondoparinux plus warfarin therapy are initiated (unless there is an absolute contraindication). Thought should be given to taking a thrombophilia screen before heparin is started when there is an unprovoked PE or if the PE is recurrent and thrombophilia has not been investigated previously.

Heparin therapy

Heparin therapy can be given either as intravenous unfractionated heparin (UFH) or low molecular weight heparin (LMWH). LMWH therapy has been shown to be at least as effective as UFH (clinically and by cost) and is probably safer than UFH for DVT and PE. The evidence for this in PE is weaker than for DVT, but the equivalence of the therapies is accepted by evidence-based care bodies such as the Cochrane Collaboration and NICE and most accept an overall benefit from LMWH compared to UFH. Dosing for enoxaparin is usually 1.5 mg/kg daily or 1 mg bd, but all LMWHs probably provide adequate therapy. Dosing must be reduced for those with poor renal function (reduced dose and frequency) and the morbidly obese (e.g. 100 kg maximum lean weight) to avoid accumulation or excessive dosing.

LMWH is particularly useful if early discharge from inpatient units or even home therapy is being contemplated. Home therapy is now widely used in North America in low-risk PE and, in well-selected cases, it seems to be safe. It is recommended in some current guidelines but relies on good risk stratification. Currently, the best validated way to predict low risk is the PESI score (see above).

Warfarin therapy

Warfarin should be started at the same time as initial heparin therapy and maintained for at least 3 months. Duration of treatment should probably be longer in those at high risk (e.g. cancer patients, unprovoked large PE, etc.). The risk of anticoagulation causing major bleeding may be as high as 10% over 6 months in very high-risk patients (2–4% in well-controlled patients), with 1–3% intracranial haemorrhage rates in some registries and mortality from bleeding of 0.1–1% pa. Risk scores for assessing who is at high risk of bleeding are not validated in the PE population and have limited evidence of discrimination. Clearly, elderly, frail, hypertensive, falling, recently bleeding, alcoholic or severely co-morbid patients are at much higher risk.

Caval interruption techniques

The use of caval interruption techniques should be considered in cases of recurrent PE despite coagulation, or where there is bleeding precluding anticoagulation. It has also been recommended for massive PE or massive leg DVT with PE. Fatal PE usually occurs as a result of further clot progressing along the inferior vena cava (IVC). Percutaneous IVC umbrellas may be inserted relatively easily and prevent further deterioration.

Patients at high risk of deterioration

Patients without cardiorespiratory instability but with features of RV strain or major PE, such as a history of syncope/collapse, ongoing hypoxia or tachycardia, elevated troponins or BNP, large clot loads, RV strain on echocardiography or clinician concern, should undergo close observation and/or continuous monitoring in a high-dependency or critical care area. There is a high rate of deterioration or death in these patients, with up to 25% requiring inotropes, intubation or thrombolysis for instability and mortality rates of up 10%. A management plan should have been decided upon before transfer out of the ED, preferably with criteria for initiation of thrombolysis/thrombectomy or catheter endarterectomy.

Unstable patients

Patients presenting with overt shock, rapidly deteriorating respiratory failure or a history of recovery from cardiorespiratory arrest should be resuscitated, stabilized and, in most cases, given thrombolysis (or alternative treatments if thrombolysis is contraindicated; see below). Severe hypoxaemia may require endotracheal intubation and ventilation. Haemodynamic instability requires gentle intravascular fluid loading with 250–500 mL boluses of crystalloids totalling no more than 1 L unless dehydration or hypovolaemia are clearly coexistent with PE. The reason for this is that, in massive PE, the right ventricle is already pressure overloaded and failing and excessive fluids will further overstretch a failing ventricle (Starling’s law).

Persistent hypotension will require inotropic support. There is little evidence to support the use of norepinephrine (noradrenaline) over epinephrine (adrenaline) as the inotrope of choice. Patients requiring inotropes should not be treated with isoprenaline as this results in vasodilatation, reduced peripheral resistance and increased cardiac output, without improving coronary perfusion.

Thrombolysis

The widespread use of thrombolytic therapy for coronary disease led to a reappraisal of thrombolytics in PE. There is definite evidence of reduced pulmonary artery pressures and improved right ventricular function after thrombolysis, which may persist following the acute episode. One small, randomized trial in shocked patients showed a clear mortality benefit for thrombolysis. In addition, some meta-analyses suggest that in the sickest patients with PE there is probably a mortality benefit. Very few clinicians would withhold thrombolytics for massive (hypotensive/unstable) PE. There is widespread use of thrombolytics in Europe for moderate-sized PE causing right ventricular strain, with some registry evidence of improved mortality or reduced complications. However, there is much less acceptance in the USA and Australia for this indication as the evidence is weak and thrombolysis is actively discouraged in haemodynamically stable, non-deteriorating patients.

Tissue plasminogen activator (rTPA) appears to be the easiest and quickest to give and to have the fewest side effects (excepting intracranial haemorrhage [ICH]) compared to urokinase and streptokinase. rTPA has been used as an infusion of 100 mg over 2 hours. Bolus reteplase (two doses of 10 units separated by half an hour) or tenectaplase (weight-based infusion) should be just as effective, although they have not been properly studied in PE and do not have TGA approval for this indication.

Thrombolysis is associated with a major bleeding episode in up to 20% of patients, with ICH rates as high as 4% and death from bleeding in 0.3–2%.

Embolectomy

Patients with persistent haemodynamic instability or hypoxia with major contraindications to thrombolysis should be considered for thoracotomy and/or embolectomy. Patients in this category are not necessarily at hospitals with facilities for cardiopulmonary bypass and, therefore, alternative therapies have been developed. The use of mechanical clot disruption (catheter embolectomy) for massive PE has been reported in case studies, but controlled studies are difficult to design because of the infrequency of the event and the emergency nature of massive PE. Unlike other surgical techniques, the expertise and equipment for this procedure are readily available in most, larger hospitals. Pulmonary embolectomy without cardiac bypass has been used as a last resort for haemodynamically unstable patients, with a reported survival of more than 50%. Following cardiac arrest, survival rates are much lower, although survivors have been reported.

There is no evidence that mechanical removal of clot results in better outcome than does thrombolysis; in fact, it could be worse. In the pre-arrest or arrested patient, the transfer to cardiopulmonary bypass may buy additional time. In general, hospitals should decide on thrombolysis versus thrombectomy as their preferred management of unstable PE to avoid confusion and unnecessary delays to management in shocked patients.

Prognosis

Prognosis is largely dependent on coexistent illness and the size and eventual position of the initial PE. Patients with cardiorespiratory arrest or shock have mortality rates of 25–50% even with thrombolysis/thrombectomy. Right ventricular strain in haemodynamically stable patients has a mortality rate of 5–15%. In addition, this group is at risk of developing chronic thromboembolism and persistent pulmonary hypertension. Patients without significant co-morbidity or signs of severity have very low rates of poor outcomes. Even with anticoagulation, hospital mortality may still be high (2.5–10%), although much of this mortality is due to co-morbidity. Recurrent PE occurs in about 25% of patients by 8 years.

Disposition

Patients with haemodynamic instability, recovery post-arrest, those with significant persistent hypoxia (<92%) and those with evidence of right ventricular strain should be admitted to an ICU or high-dependency unit. Most patients with stable PE can be admitted directly to the ward. Early discharge on LMWH (or Fondoparinux) should be considered for compliant patients with smaller PEs, good home circumstances and a low risk of complications.

5.6 Pericarditis, cardiac tamponade and myocarditis

Pericarditis

Introduction

Pericarditis may be acute, subacute or chronic. It is defined as inflammation of the pericardium. It should be noted, however, that the condition is better described as perimyocarditis. In the majority of cases, there are variable degrees of associated ‘epimyocarditis’, which has important clinical implications. The causes of pericarditis are listed in Table 5.6.1.

Clinical features

History

Idiopathic or viral types may have a history of a recent viral illness and the history should be directed towards the known causative pathologies. The pain is usually retrosternal, sometimes with radiation to the trapezius muscle ridges, but not generally to the arms. It may also be pleuritic in nature, and worse with movement and respiration. It is typically worse when lying supine and better when sitting up and leaning forward. True dyspnoea is not a feature unless there are secondary complications, such as cardiac tamponade or chronic constrictive pericarditis. Dyspnoea may also be due to the underlying disease process causing pericarditis. Respiration may however be shallow because of pain.

Examination

With viral or idiopathic types, fever may be present. Sinus tachycardia is common. A pericardial friction rub may be heard, caused by rubbing between parietal and visceral pericardial layers or between parietal pericardium and lung pleura. A rub may therefore be heard even with the presence of a large effusion. It may be audible anywhere over the precordium, but is best heard with the diaphragm of the stethoscope over the lower left sternal edge, where the least amount of lung tissue intervenes between the pericardium and the chest wall, with the patient leaning forward in full expiration. The rub has a superficial scratching or ‘Velcro-like’ quality. Rubs may be difficult to detect, as they can be transient and migratory. The patient should be examined for any signs of a complicating cardiac tamponade. A search should also be made for any signs of an underlying causative condition.

Temperature above 38°C is uncommon and may indicate purulent (i.e. bacterial) pericarditis, a much more serious condition.

High-risk features

The following high-risk clinical features should raise suspicion of serious underlying pathology, such as tuberculosis or other bacterial infection, malignancy or autoimmune disease:

Clinical investigation

Blood tests

Chest X-ray

Chest X-ray does not confirm the diagnosis of pericarditis but may rule out other causes of pleuritic chest pain. It may also find evidence of a complicating pericardial effusion or evidence of causative pathology, such as malignancy.

ECG

The ECG is the most important investigation and will show abnormalities in 90% of patients with acute pericarditis. ECG changes are the result of the associated epimyocarditis. The pericardium is electrically neutral and does not produce ECG changes. Therefore, in the occasional ‘pure’ case of pericarditis, the ECG will be normal. It may follow the typical evolution of changes, but in a sizeable minority will not.

The typical pattern follows four stages:

Atypical ECGs may include the following:

Echocardiography

This may give indirect evidence for pericarditis by showing the presence of an effusion or a thickened pericardium. High-quality echocardiograms are able to distinguish bloody from serous effusions. Transoesophageal echocardiography (TOE) is better at measuring thickness of the pericardium than transthoracic echocardiography (TTE). A normal echocardiogram does not rule out a diagnosis of pericarditis.

Computed tomography (CT) scan/magnetic resonance imaging (MRI)

CT and MRI have the advantages of a larger field of view and excellent imaging of anatomy that is not possible with echocardiography. They also have high soft-tissue contrast. In most patients, they provide excellent images of the pericardium, including thickness, the presence of effusions and any pericardial lesions.

Pericardiocentesis and biopsy

Rarely required, pericardiocentesis and biopsy may be indicated in selected cases. Indications include suspected serious underlying pathology, such as a bacterial, tuberculous or neoplastic pericarditis, when cardiac tamponade is present or in chronic or recurrent cases for diagnostic purposes.