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Cardiovascular disorders 

Cardiovascular disorders
Cardiovascular disorders

Carl Waldmann

, Andrew Rhodes

, Neil Soni

, and Jonathan Handy

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date: 22 April 2021

Chapter contents



Hypertension is currently defined as sustained elevation of systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg (Table 19.1). In the UK, the prevalence of hypertension is ~32%. Of these, only 22% have controlled BP (<140/90 mmHg). Essential (primary) hypertension accounts for 80–90% of cases. Secondary causes of hypertension include endocrine and renal disorders and drug-induced hypertension (Box 19.1).

Table 19.1 British Hypertension Society (BHS) definitions of hypertension



Optimal BP



Normal BP



High–normal blood pressure



Grade 1 hypertension (mild)



Grade 2 hypertension (moderate)



Grade 3 hypertension (severe)



Reproduced from The BMJ, 328, Williams B., Poulter P.R, Brown M.J, et al. British Hypertension Society guidelines for hypertension management 2004 (BHS-IV) summary. Copyright (2004) with permission from BMJ Publishing Group Ltd.

Treatment of uncomplicated essential hypertension

First-line therapy

Young and non-black individuals tend to have higher activity of the renin–angiotensin–aldosterone system (RAAS), as evidenced by higher plasma renin (PR). They respond well to angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), whereas those with a low PR, i.e. the elderly and Afro-Caribbean individuals, respond better to either calcium channel blockers (CCBs) or diuretics (Figure 19.1).

Figure 19.1 The BHS/NICE recommendations for combining BP-lowering drugs. A, ACE inhibitors or ARBs; C, CCB; D, diuretics.

Figure 19.1 The BHS/NICE recommendations for combining BP-lowering drugs. A, ACE inhibitors or ARBs; C, CCB; D, diuretics.

© NICE (2011) CG127 Hypertension in adults: diagnosis and management. Available from All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication.

Drug combinations

BP control on monotherapy is rarely achieved. The most effective way to control BP is to combine two or more antihypertensive agents that lower BP by different mechanisms. ACE inhibitors or ARBs (A) combine well with CCB (C) and diuretics (D). This gives rise to the A/CD rule for combining drugs, in which a drug from the A group is added to another from either the C or D groups (Figure 19.1). The next step is to add a drug from each group: A + C + D. If the BP is not controlled on this combination, then patients are diagnosed with resistant hypertension. The recent PATHWAY 2 study has shown that the addition of spironolactone may be effective in controlling BP in patients with resistant hypertension.

Management of hypertension in different patient groups

The elderly

Low-dose thiazide diuretics are the preferred first-line treatment. Dihydropyridine CCBs are suitable alternatives when thiazides are contraindicated or not tolerated.

The very elderly

No firm evidence exists to guide treatment for patients above the age of 80 years. If antihypertensive treatment has been started before the age of 80, they should be continued.

Diabetes mellitus

Type 2 diabetes

ACE inhibitors and ARBs have an antiproteinuric effect and delay progression from microalbuminuria to overt nephropathy. Combined use of ACE inhibitors and ARBs is not advised any more as serious side-effects, including hyperkalaemia and acute kidney injury, are a potential risk.

Type 1 diabetes

ACE inhibitors have a specific renoprotective action independent of the BP-lowering effect. ACE inhibitor therapy should be titrated to the maximum tolerated recommended dose.

Ethnic groups

Afro-Caribbean hypertensive subjects are more responsive to diuretics and CCBs. ACE inhibitors and ARBs in monotherapy may be less effective in blacks because the RAAS is frequently suppressed, but when these drugs are combined with a diuretic or a CCB they are quite effective.

Hypertensive crises

A hypertensive crisis is defined as severe hypertension with ongoing or impending target organ damage. The rate of the rise in BP in relation to the previous levels of BP is more important than the absolute BP level. A hypertensive emergency is defined as a situation that requires immediate BP lowering (not necessarily to normal values) to prevent or limit target organ damage. Hypertensive urgency is a situation in which severely elevated BP is not accompanied by any evidence from the history, physical examination, or laboratory investigations of acute target organ damage. Individuals under this category could be:

  1. 1. Known hypertensive patients who are not compliant with their medication; prior therapy should be restarted (if there are no side-effects).

  2. 2. For patients taking their medications regularly, therapy should be increased (either by increasing the dose(s) of drugs or by adding new drugs).

  3. 3. For patients on no treatment, hypertension therapy should be started with oral agents (e.g. nifedipine sustained [SR] or modified release [MR]) and a follow-up appointment arranged urgently with a hypertension clinic.

Individuals with untreated severe or accelerated hypertension have a dreadful long-term prognosis if their high BP is not treated properly. The most common causes of death are renal failure, stroke, and myocardial infarction (MI).

Management of hypertensive emergencies

The key to a successful outcome is the prompt recognition and initiation of treatment. Full medical history and physical examination, including palpation of all peripheral pulses and a fundoscopic examination, is mandatory. Specific points in the patient’s past medical history include the patient’s BP prior to presentation and drug history (including prescription, over-the-counter, and recreational drugs).

Initial investigations should include full blood count (FBC), electrolytes, urea, creatinine, urine dipstick, chest X-ray (CXR), and electrocardiograph (ECG). These tests should be performed simultaneously with the initiation of the antihypertensive therapy.

The approach in treating hypertensive emergency is initially to reduce BP by ~20–25%, with further reductions accomplished more gradually. The initial reduction should be achieved over a period of 2–4 h, with less rapid reduction over the next 24 h.


A sudden increase in peripheral vascular resistance (PVR) (e.g. secondary to non-compliance) triggers an increase in circulating levels of vasoconstrictor substances such as angiotensin II and noradrenaline.

Aortic dissection

Aortic dissection must be excluded in any patient presenting with severe hypertension and chest pain, back pain, or abdominal pain. The condition is life-threatening, with a very poor prognosis if not adequately treated (mortality is 1%/h). Aortic dissection is classified as type A if it involves the ascending aorta or type B if it does not. Surgical treatment is usually required for type A dissection, whereas type B responds more favourably to medical treatment. Severe refractory hypertension is nearly omnipresent, especially in the acute phase even in patients without a history of hypertension.

Propagation of the dissection is dependent not only on the elevation of the BP itself, but also on the velocity of left ventricular (LV) ejection and the rate of increase of the aortic pulse wave. Therefore, the immediate reduction of BP and shear stress is of paramount importance to prevent the extension, haemorrhage, and rupture of the dissection. BP should be reduced quickly (within 15–30 min) to the lowest tolerated level that preserves adequate organ perfusion. The initial treatment of choice is a combination of intravenous (IV) β‎-blocker (e.g. esmolol or metoprolol) or a combined α‎–β‎-blocker (e.g. labetalol) and a vasodilator (e.g. sodium nitroprusside [SNP] or dihydropyridine CCB). The recent CAFÉ trial, a substudy of the ASCOT trial, has shown that a combination of a dihydropyridine CCB and an ACE inhibitor was more effective in reducing central aortic pressure than a combination of a β‎-blocker and a diuretic. Therefore, the combination of a CCB and an ACE inhibitor should be considered in the treatment.

Acute pulmonary oedema

More than 90% of patients with heart failure (HF) have a history of hypertension. The clinical syndrome of HF is usually characterized by signs and symptoms of intravascular and interstitial volume overload. IV glyceryl trinitrate (GTN) is the drug of choice in the initial treatment, together with an IV loop diuretic (e.g. furosemide) and diamorphine. GTN reduces both preload and afterload while improving coronary bloodflow. There is very little clinical experience with the use of ACE inhibitors in patients with acute LV failure, but a short-acting ACE inhibitor (e.g. captopril) may be added if necessary.

It is important to stress here that patients with malignant hypertension who present with acute (flash) pulmonary oedema may not have volume overload. In fact, they may have volume depletion secondary to pressure natriuresis. Therefore, IV diuresis may exacerbate the hypertension and cause further clinical deterioration. The use of diuretics should be reserved for patients who are clinically fluid-overloaded and should not be prescribed routinely.

ST-elevation myocardial infarction and acute coronary syndrome

Hypertension is very common in patients presenting with acute coronary syndrome (ACS). The overall prevalence of hypertension in US patients presenting with non-ST-elevation myocardial infarction (NSTEMI) is ~50%, while in Europe the prevalence is ~34%.

IV GTN is the drug of choice for ACS and ST-elevation myocardial infarction (STEMI) as it reduces PVR while improving coronary perfusion. β‎-Blockers attenuate the activity of the adrenergic system and the RAAS, and improve survival in post-MI patients. In ACS, IV β‎-blockers should be started then switched to oral when the patient is stable. When β‎-blockers are contraindicated, a non-dihydropyridine CCB (diltiazem or verapamil) can be used if the patient does not have severe LV dysfunction. Short-acting dihydropyridine CCB should not be used in the treatment of a hypertensive crisis when associated with ACS or acute STEMI. ACE inhibitors could be added if hypertension persists, as they significantly improve survival during STEMI. SNP, unlike GTN, increases heart rate and provokes ST-segment elevation, and should not be used alone.

Cocaine overdose

Cocaine overdose is often associated with uncontrolled severe hypertension and coronary artery vasoconstriction, leading to angina, MI, or sudden death. These effects are mediated through α‎-adrenergic receptors and therefore β‎-blockers alone (i.e. without α‎-blockers) may exacerbate the hypertension and the clinical condition, and are therefore contraindicated. A non-dihydropyridine CCB (e.g. diltiazem or verapamil) or a combined α‎–β‎-blocker, e.g. labetalol, may be used.

Severe pre-eclampsia and eclampsia

Pre-eclampsia is defined as hypertension (BP ≥140/90 mmHg) in the second half of pregnancy (i.e. after 20 weeks of gestation) associated with proteinuria and oedema. Eclampsia is the occurrence of seizures in a patient with pre-eclampsia. Treatment with antihypertensive drugs is not usually indicated in pregnancy for BP <160/100 mmHg. ACE inhibitors and ARBs are contraindicated in pregnancy because of the increase in foetal and neonatal morbidity and mortality. Methyldopa remains the mainstay of treatment for patients with moderate gestational hypertension because of its foetal and neonatal safety. The drug, however, has many adverse side-effects. Labetalol and nifedipine may be considered if methyldopa is contraindicated or not tolerated.

For pre-eclamptic patients with severe hypertension, IV hydralazine or labetalol could be given. SNP can cause profound reflex paradoxical bradycardia and hypotension, and should be avoided.

Malignant hypertension

Malignant (accelerated) hypertension is a syndrome characterized by severely elevated BP accompanied by retinopathy (including exudates, haemorrhages, or papilloedema), nephropathy, encephalopathy, and microangiopathic haemolytic anaemia. Pathologically it is characterized by fibrinoid necrosis in arterioles, myointimal proliferation in small arteries, platelet and fibrin deposition, and breakdown of normal vascular autoregulation function. The resulting vasoconstriction induces severe elevation in BP and widespread endothelial damage. The resulting renal ischaemia prompts massive release of renin and angiotensin II, triggering a vicious cycle. The rapid increase in BP enhances pressure natriuresis, which further stimulates the RAAS, resulting in secondary hyperaldosteronism, hypokalaemia, and metabolic alkalosis.

Malignant hypertension rarely occurs de novo, and is usually a consequence of untreated essential or secondary hypertension such as renal artery stenosis, phaeochromocytoma, or scleroderma. The incidence of malignant hypertension remains stable across the UK and Europe, with ~1–2 cases per 100 000 per year. Malignant hypertension has a very poor prognosis if untreated, with a mortality rate >90% within 1 year, but, with proper treatment, 5-year survival is 60–75%. Most patients who present with malignant hypertension have volume depletion secondary to pressure natriuresis. Therefore, further diuresis may exacerbate the hypertension and cause further deterioration in kidney function.

Hypertensive encephalopathy

Hypertensive encephalopathy is much less common these days with the use of modern antihypertensive drugs. It is believed to be due to cerebral oedema secondary to failure of cerebral blood flow (CBF) autoregulation and rapid elevation of cerebral perfusion. Symptoms and signs include headache, nausea and vomiting, visual disturbances, altered level of consciousness, confusion, disorientation, focal or generalized seizures and retinopathy including papilloedema. Diagnosis may be difficult as it is one of exclusion requiring that stroke, encephalitis, vasculitis, subarachnoid haemorrhage and mass lesions to be excluded first. The definite criterion to confirm the diagnosis is a prompt improvement in the patient’s clinical condition with the response to antihypertensive treatment. The goal of treatment is to reduce BP by ~25% within the first hour or to a level of 160/100 mmHg, whichever value is higher. It must be emphasized that cerebral hypoperfusion and neurological deterioration may result if more reductions in BP are achieved quickly. In this case, BP should be allowed to increase and further reductions should be attempted more slowly.


There is a high prevalence of apparent treatment-resistant hypertension among hypertensive individuals with history of stroke or transient ischaemic attack. Appropriate treatment of hypertension in the setting of acute stroke remains contentious. There is little scientific evidence and no clinically established benefit for rapid lowering of BP among persons with acute ischaemic stroke. Aggressive lowering of BP may cause neurological worsening and there is a need for more individualized BP monitoring and management. However, it is generally agreed that severe hypertension (BP >180/110 mmHg) may be an indication for treatment, as higher BP levels are a contraindication to IV thrombolysis. If thrombolysis is not considered, then emergency administration of antihypertensive drugs should be withheld unless the SBP is >220 mmHg and/or DBP is >120 mmHg. Treatment could be started with IV labetalol.

A reasonable goal would be to lower BP by 25% within the first day. Previously hypertensive patients with mild to moderate strokes who are not at high risk for increased intracranial pressure may have their usual prestroke antihypertensive medications restarted 24 h after their stroke.

Drugs for the treatment of hypertensive emergencies


SNP dilates arteriolar resistance and venous capacitance vessels and decreases both the afterload and preload. It is a very potent agent, with an immediate onset and short duration of action; plasma half-life is 2–3 min. Continuous arterial BP monitoring is recommended to avoid overreduction of BP. The drug is light-sensitive and should be shielded from light to prevent degradation. The usual dose is 0.3–10 µg/kg/min. Cyanide poisoning may occur with prolonged or high-dose administration, especially in individuals with renal or hepatic insufficiency. Manifestations of poisoning include central nervous system depression, seizures, and lactic acidosis.


GTN dilates arteriolar resistance and venous capacitance vessels. It reduces preload and afterload, improves LV function, and reduces myocardial oxygen demand. GTN dilates both epicardial coronary vessels with stenosis and collaterals, and increases blood supply to ischaemic areas. It is the drug of choice for reducing BP in individuals with STEMI, ACS, and acute pulmonary oedema. However, the BP-lowering effect of GTN is not as predictable as with SNP, and higher doses (up to 300 µg/min) may be required to achieve an adequate response. Onset of action is almost immediate, with a very short duration of action (half-life 3–5 min). The starting dose is 5–15 µg/min. Nitrate tolerance is a problem even within the first 24 h.


Labetalol is a selective α‎1- and non-selective β‎-adrenergic receptor blocker. Its differential effects on α‎:β‎ receptors are 1:3 after oral administration and 1:7 after IV administration, respectively. The drug can be given IV as a 20–80-mg minibolus injection (q 10 min) or 2–4-mg/min infusion. Labetalol produces a prompt and controlled reduction in BP in patients with hypertensive crises, with onset of action within 5 min and duration of action of 3–6 h. The drug is contraindicated in patients with acute LV failure, heart block, and chronic obstructive pulmonary disease.


Esmolol is an ultrashort-acting β‎1-selective adrenergic blocking agent with an extremely brief half-life of <10 min. This agent is available for IV use both as a bolus and as an infusion. The recommended loading dose is 0.5–1 mg followed by an infusion of 50–200 µg/kg/min.



A tachycardia is an excessive heart rate, usually defined as >100 bpm (adults), arising from either the atria or the ventricles. Tachycardias are associated with increased incidence of major cardiac events and length of intensive care unit (ICU) stay.

Pathological tachyarrhythmias may be an asymptomatic finding on cardiac monitoring or may present as palpitations, syncope, hypotension, or cardiac arrest. Whatever the cause, it is imperative to optimize physiological status and identify and correct potential precipitant (Table 19.2). The mainstay of treatment is rate control and restoration of sinus rhythm with either antiarrhythmic drugs or electrical cardioversion. If associated with adverse clinical signs, immediate intervention is indicated.

Table 19.2 Common potential precipitants for tachyarrhythmias



Common clinical examples


K+ (aim 4.0–4.5 mmol/l)

Mg++ (aim >0.8–1.2 mmol/l)


Metabolic acidosis

Postsurgery, bowel obstruction, potassium-sparing diuretics

Volume status




Diarrhoea, dehydration, sepsis



Myocardial ischaemia

Coronary artery disease

Postintervention—percutaneous coronary intervention, cardiac surgery

Prolonged arrhythmia in pre-existing HF

Hypoxia (hypercarbia)




Sepsis, drug reaction

Pacemaker failure


Sympathetic drive

Pain, agitation

Common pathological arrhythmias and management

Atrial fibrillation

Atrial fibrillation (AF) is characterized by uncoordinated atrial activation (Table 19.3).

Table 19.3 Comparison of arrhythmia characteristics



ECG features


Risk factors


Following 4–6 re-entry circuit wavelets in the atria near anatomical/ functional barriers

Absent P waves; fibrillatory waves and irregular ventricular response (intact AV conduction)

4–5% General ICU 25–40% Cardiac ICU

Age, diabetes, hypertension, structural and ischaemic heart disease, cardiac failure, changes in intravascular volume, increased sympathetic activity, inotropic agents, intracardiac lines, electrolyte imbalance, lung disease, systemic inflammatory response syndrome, hyperthyroidism


multiple re-entrant/ectopic atrial waves

Regular ‘saw-tooth’ atrial deflexion waves best seen in leads II, III and aVF

5.2% General ICU

As AF, plus pericarditis

Multifocal atrial tachycardia

? Triggered activity due to intracellular calcium overload or delayed ‘after depolarization’

Atrial rate >100 bpm and >3 morphologically distinct P waves. P–P intervals are irregular and there is an isoelectric base line between P waves

0.05–0.32% inpatients. ICU incidence not known—probably underdiagnosed

Chronic obstructive pulmonary disease, hypoxaemia, pulmonary embolism, congestive HF, and electrolyte imbalance


Originates from one or more ventricular ectopic foci, rate >100 bpm

Wide QRS complexes (>140 ms), negative precordial, independent atrial activity, capture and fusion beats

41% General ICU

Cardiac disease, acute ischaemia electrolyte imbalance, hypoxaemia, acidaemia, drugs, trauma


Cycles of alternating electrical polarity with electrical axis rotating around the baseline

Characteristic paroxysms of 5–20 beats at heart rate greater than 200 bpm and alternating electrical axis in 10–12 beats

Not known

Risk factors: drugs, electrolyte imbalance, subarachnoid haemorrhage, QTc prolongation, and insecticide poisoning

Management principles

  • Restoration of sinus rhythm if possible (chemical/electrical cardioversion).

  • Prevention/exclusion of intracardiac thrombus (transoesophageal echocardiography)—anticoagulation if AF >48 h.

  • Rate control (amiodarone/β‎-blocker/calcium channel blockade) where cardioversion not possible.

  • Ongoing anticoagulation may be required and should be tailored to the individual patient situation—consider CHA2DS2-VASc and HAS-BLED scores to risk-stratify for stroke thromboprophylaxis.

Prophylaxis and maintenance of sinus rhythm

  • Postcardiothoracic surgery: risk of AF is reduced by amiodarone, β‎-blockade, or diltiazem. Digoxin should not be used.

  • In postoperative AF, rhythm control should be the initial goal.

  • If antiarrhythmics are required to maintain sinus rhythm, β‎-blockade/amiodarone may be considered.

Atrial flutter

Atrial flutter (AFL) is the expression of rapid and regular atrial excitation (Table 19.3).

Management principles

  • Generally, as for AF.

  • Digoxin may convert to AF (rate control is easier).

  • Overdrive atrial pacing may be used to cardiovert (success rate <50%).

Multifocal atrial tachycardia

Multifocal atrial tachycardia is an irregular cardiac rhythm caused by at least two different sites of competing atrial activity with the sinus node (Table 19.3).

Management principles

  • Frequently transient. May spontaneously convert to sinus rhythm, AF or AFL.

  • Treat any precipitating cause.

  • Antiarrhythmics (β‎-blockers, magnesium, or verapamil) may be used.

  • Electrical cardioversion is not generally effective.

Pre-excitation syndromes

These are characterized by intermittent tachycardia (narrow or broad complex) associated with an accessory atrioventricular (AV) connection where a re-entry circuit between atria and ventricles occurs. Includes the Wolf–Parkinson–White syndrome, where first manifestation is cardiac arrest in 50%. (Note that a pre-excitation delta wave is seen in only 3/1000 ECGs.) The development of AF in Wolf–Parkinson–White is life-threatening as the risk of degeneration to ventricular fibrillation (VF) is high.

Management principles

  • Adenosine should be avoided.

  • Early consultation with an electrophysiologist is advised for the ICU patient with a pre-excitation syndrome.

  • Electrical cardioversion should be used in emergency.

Ventricular tachycardia

Ventricular tachycardia (VT) is characterized by a regular broad-complex tachycardia (Table 19.3).

Management principles

  • In all cases, correct/remove potential cause(s) and optimize medical management of cardiac disease.

  • Non-sustained VT with haemodynamic compromise: consider lidocaine/amiodarone infusion or ventricular pacing.

  • Sustained VT with no haemodynamic compromise:

    • Cardioversion

    • Amiodarone

    • Lidocaine—avoid if left-ventricular ejection fraction (LVEF) <35%

    • Procainamide/flecainide—if no myocardial ischaemia or HF

    • LV fascicular VT (right bundle branch block [RBBB] morphology and left axis deviation) l IV verapamil or β‎-blocker

    • Post-STEMI or -NSTEMI consider β‎-blocker if no additional risk factors for shock (age >70, heart rate >110 bpm, SBP <120 mmHg l increased mortality).

  • Sustained VT with haemodynamic compromise—cardioversion ± IV amiodarone (± sedation).

  • Polymorphic VT with normal QT interval:

    • May be associated with myocardial ischaemia: electrical cardioversion is recommended with a plan for revascularization where possible

    • β‎-Blocker

    • Amiodarone IV

    • Lidocaine IV—if unresponsive to above.

  • Torsade de pointes (TdP): main features described in Table 19.3. In addition to correction/removal of potential causes, give IV magnesium. Consider overdrive pacing or isoprenaline.

  • Catheter ablation—for sustained monomorphic VT with:

    • Scar-related disease with incessant VT or electrical storm

    • Ischaemic heart disease and recurrent implantable cardioverter defibrillator (ICD) shocks due to sustained VT.


VF is characterized by an irregular broad and/or narrow complex tachycardia. The main features are described in Table 19.3.

Management principles

Defibrillation and cardiopulmonary resuscitation as per Advanced Life Support/International Liaison Committee on Resuscitation guidelines.

Non-pharmacological interventions

Ablative therapy

This involves the destruction of abnormal conduction pathways within the heart using high-frequency alternating currents or radiofrequency. It is now indicated as first-line therapy for several atrial and ventricular arrhythmias, particularly where drug therapy is not tolerated or risk of sudden cardiac death is high.

Surgical ablation may be considered in specialist centres for those refractory to antiarrhythmic therapies and/or failed catheter ablation, particularly if an LV aneurysm is present post-MI.

Implantable devices

Cardiovertor defibrillators are indicated in survivors of VF arrests or those at risk of sudden cardiac death. They can terminate but not prevent arrhythmia recurrence. Concomitant therapy with β‎-blocker (± amiodarone) is indicated to minimize both appropriate and inappropriate ICD interventions (shocks). Guidelines for use of implantable devices are well established. Discussion with an electrophysiologist/HF specialist is mandated.

Key points

  • Treatment of all tachyarrhythmias on the ICU should include correction/removal of potential causes.

  • Restoration of sinus rhythm is the main goal.

  • All antiarrhythmic drugs are potentially proarrhythmogenic.

  • Where standard pharmacological or electrical therapy fails, expert advice should be sought from an electrophysiologist as specialist intervention may be required.



A slow ventricular rate, usually defined as below 60 bpm, may be absolute (<40 bpm) or relative (excessively slow for the patient’s clinical status). Bradyarrhythmias are due to either sinus node dysfunction or AV conduction disorders. The main physiological effect is to reduce cardiac output, which may be compensated for by an increase in stroke volume.

Causes of bradyarrhythmias

The commonest causes of symptomatic bradyarrhythmia include adverse drug effects, acute MI, intoxication, and electrolyte disorder. These are divided into intrinsic (paroxysmal AV block, sinoatrial block, and sinus arrest [including the brady–tachy form of sick sinus syndrome] AF with slow ventricular conduction) and extrinsic (vagal induced sinus arrest or AV block, idiopathic AV block [adenosine-mediated] hypothermia, and metabolic). Bradyarrhythmia is common in intensive care settings. It is usually transient and is often related to extrinsic factors such as drugs and airway manipulation.

Factors that increase the likelihood of arrhythmia in ICU include:

  1. 1. Pre-existing cardiac disease.

  2. 2. Treatment with antiarrhythmics.

  3. 3. Recent macrovascular event.

  4. 4. Microvascular disease causing ischaemia.

  5. 5. Altered acid–base balance.

  6. 6. High CO2.

  7. 7. Abnormal electrolyte balance.

  8. 8. Endogenous catecholamines (pain, anxiety).

  9. 9. Exogenous catecholamines (inotropes).

  10. 10. Suction/bronchoscopy/airway manoeuvres.

  11. 11. Deep anaesthesia/sedation.

  12. 12. Anaesthesia drugs (muscle relaxants, regional).

Sinus node dysfunction (sick sinus syndrome)

  • 1:600 patients > 65 years.

  • Multiple ECG manifestations, including sinus bradycardia, sinus arrest, sinoatrial block, tachy–brady syndrome, AF.

  • Commonest manifestation in the ICU is excessive bradycardia upon treatment of tachyarrhythmia.

  • Sinus node dysfunction post-anterior MI is relatively common (5–30%). Often associated with concomitant AV nodes block. Treatment is usually not required unless associated with cardiac failure, hypotension, or continuing myocardial ischaemia.

  • In tachy–brady syndrome, pharmacological intervention to control the ventricular rate during tachycardia by blocking AV conduction with β‎-blockers, calcium channel blockers or digitalis may not be possible without pacing due to sinus node depression.

AV conduction disturbance

  • Abnormalities arise in the AV node or the bundle of His.

  • Multiple ECG manifestations, including first-/second-/third-degree AV block, bundle branch block, fascicular block.

  • Narrow QRS implies block in the AV node, wide QRS implies infranodal block.

  • Commonest cause focal injury (MI), but may result from right heart catheter-related trauma.

  • Where seen in conjunction with aortic endocarditis, may indicate aortic root abscess with risk of progression to high-grade AV block.

  • Myocardial ischaemia should be excluded with development of new bundle branch block (BBB). BBB in anterior MI may result from large infarct size, LV dysfunction, or conduction abnormalities. It is associated with poor prognosis.

  • First-degree (PR interval >0.2 s): does not normally require intervention.

  • Second-degree (Mobitz type I, Wenckebach): progressive lengthening of PR interval until failed conduction.

  • Second-degree (Mobitz type II): constant PR interval with intermittent failure of conduction.

  • Third-degree (complete heart block): independent atrial and ventricular activity.

Risk of progression to high-grade block

The risk of progression to high-grade AV block and to asystole needs to be assessed in all patients with AV conduction disturbances. Where indicated, back-up pacing should be considered:

  • First-degree and Mobitz type I second-degree AV block—low risk.

  • Mobitz type I second-degree AV block with wide QRS—high risk, especially in the context of anterior MI.

  • Mobitz type II second-degree AV block with wide QRS or associated with anterior MI—high risk

Specific conditions

Infective endocarditis

Development of new AV block or BBB in infective endocarditis implies an aortic root abscess, usually in the non-coronary cusp. This complication is associated with significant risk of abrupt development of high-grade AV block. Where diagnosed, immediate provision of potential for transcutaneous pacing is indicated, and urgent temporary pacing wire insertion may be required. The case should be discussed with the endocarditis team as a matter of urgency.

Lyme disease

AV block is the commonest manifestation of myocarditis in this condition. Antibiotic treatment usually resolves the AV block but temporary pacing may be required.

Clinical approach

Although the clinical approach to the ICU patient with bradycardia does not differ from that in the non-ICU setting, the thresholds at which intervention may be indicated differ and have to be tailored to the individual. Principles of management include exclusion/removal of potential causes, assessment of the haemodynamic impact of the bradycardia, and special investigations, while rapidly assessing full clinical status of patients. Further principles of management follow:

  1. 1. Immediate intervention may not be required if the patient is haemodynamically stable.

  2. 2. Correct electrolytes and ensure adequacy of oxygenation and ventilation. This should be carried out simultaneously with other treatment if haemodynamically compromised. Serum potassium should generally be maintained at >4.5 mmol/l in patients with cardiac disease or postcardiac surgery (excluding postcardiac transplantation).

  3. 3. Treat all reversible ischaemia. Acute MI must be considered as a cause of bradyarrhythmia and managed according to current guidelines.

  4. 4. If the rate is slow and the patient haemodynamically compromised then consider pacing. Indications for pacing are discussed in the section on ‘Pacing’.


Intermittent sinus node dysfunction may respond to a small dose of atropine but the response is unpredictable. With prolonged bradyarrhythmia and severe, aggravating ventricular irritability not responding to atropine or isoprenaline, temporary pacing should be considered. The following drugs can be used to treat bradyarrhythmia.


  • Class: muscarinic anticholinergic agent. Synthetic quaternary amine with no central effect.

  • Indications: treatment of bradycardia, antisialogogue.

  • Dose: 200–600 µg IV bolus. Peak effect occurs 3 min after intravenous injection.

  • Adverse effects: dry mouth, inability to sweat, fever.


  • Class: muscarinic anticholinergic agent. Naturally occurring tertiary amine which penetrates blood–brain barrier.

  • Indications: treatment of bradycardia when associated with haemodynamic compromise or ventricular ectopy.

  • Dose: 0.02 mg/kg. Repeat in 5 min if required. 3 mg is needed for complete vagal blockade in adult.

  • Adverse effects: dry mouth, inhibition of sweating, difficulty swallowing, hallucination, blurred vision.

  • Contraindication: glaucoma.


  • Class: short-acting synthetic catecholamine with pure β‎-adrenergic stimulating properties (β‎1 > β‎2).

  • Indications: in emergencies to increase heart rate in bradycardia or in heart block.

  • Dose: 0–10 µg/min.

  • Adverse effects: reduction in DBP, headache, tremor, palpitations, arrhythmia, and sweating.


  • Class: β‎- and α‎-adrenergic receptor agonist.

  • Indication: asystole, inotropic therapy, anaphylactic reaction, acute severe asthma.

  • Dose: for bradyarrhythmia 5–10 µg IV bolus via central vein. Followed if necessary by infusion 0.01–0.2 µg/kg/min.

  • Interaction: exaggerated pressor and tachycardiac response with other sympathomimetics.

  • Adverse effects: tachycardia, hypertension, vasoconstriction, arrhythmia, hyperglycaemia, thrombophlebitis/necrosis if given via peripheral vein.


Pacing can be a definitive life-saving treatment for bradyarrhythmia. Various modes of pacing are available, including mechanical, transcutaneous, transvenous, transoesophageal, and transthoracic. Although a change in drug therapy should be considered for drug-induced bradyarrhythmia, pacing may be an acceptable approach if no agent with equivalent efficacy is available. Current recommendations are that temporary transvenous pacing should be avoided as far as possible, and, when used, treatment time should be as brief as possible. Atrial pacing is preferred in patients with sinus node dysfunction as it reduces the incidence of AF, pacemaker syndrome, and thromboembolism. In principle:

  1. 1. Temporary transvenous pacing should not be used routinely—only where chronotropic drugs are insufficient.

  2. 2. Positive chronotropic drug infusion may be preferred for a limited time (provided there are no contraindications).

  3. 3. Temporary transvenous pacing should be limited to cases of: a) high-degree AV block without escape rhythm; b) life-threatening bradyarrhythmias (i.e. during interventional procedures, acute MI, drug toxicity of concomitant systemic infection.

  4. 4. If an indication for permanent pacing exists, this should be implanted as soon as possible.

Indications for pacing in the general ICU

  1. 1. Symptomatic sinus bradycardia (SBP <80 mmHg) unresponsive to drug therapy.

  2. 2. Mobitz type II second-degree AV block.

  3. 3. Third-degree AV block.

  4. 4. Bilateral BBB (alternating BBB or right BBB with alternating left anterior fascicular block/left poster.

  5. 5. Newly acquired or age-indeterminate bifascicular block with first-degree AV block.

  6. 6. Newly acquired AV block or BBB in infective endocarditis.

Indications for pacing in acute MI

A degree of AV block occurs in 12–25% of acute MI, commonly associated with inferoposterior MI causing AV nodal ischaemia with right ventricular (RV) impairment. The sinus and AV nodes are relatively resistant to permanent injury by infarction and normal function should recover over time. However, permanent damage occurs more readily to the bundle of His. Anterior MI often causes AV nodal block in the bundle of His and it can progress suddenly to complete heart block. Therefore, even transient complete AV block in the His–Purkinje system due to infarction justifies the insertion of a pacemaker.

  1. 1. AV block post-anterior MI associated with cardiac failure, hypotension, or continuing myocardial ischaemia.

  2. 2. First-degree AV block and BBB associated with anterior MI.

  3. 3. Newly acquired bifascicular block associated with anterior MI.

  4. 4. Alternating BBB with anterior MI.

Indications for pacing after cardiac surgery

AV block is a significant complication of cardiac surgery, particularly postvalve replacement and in surgery for congenital heart disease (1–3%). Epicardial wires are inserted perioperatively for the management of arrhythmias (bradycardia, nodal/junctional arrhythmia, AV block) associated with haemodynamic compromise and those who are at high risk of postoperative arrhythmia.

Myocardial infarction: diagnosis


Coronary artery disease (CAD), also known as ischaemic heart disease, is manifest clinically as chronic stable angina or ACSs. ACSs are divided into STEMI, NSTEMI, or unstable angina (UA). NSTEMI and UA share clinical features upon presentation but are ultimately distinguished by elevation of biomarkers denoting myocardial injury in NSTEMI. The broad array of ischaemic heart diseases remains the leading cause of mortality in adults in industrialized countries across the globe.

Patients with chest pain are responsible for a large proportion of all hospitalizations in Europe. Rapid distinction of the relatively small subset of patients that actually have ACS from non-cardiac causes is essential, as the ACS group has a significant rate of death, MI, and readmission despite modern therapy. ACS patients share the common pathophysiology of atherosclerotic plaque rupture or erosion with superimposed thrombus and distal embolization. Since this pathophysiology is life-threatening, clinical risk stratification protocols have been well established and, via guidelines, drive clinical therapy. Two categories of ACS patients have emerged based upon the ECG:

  1. 1. Patients with acute chest pain lasting > 20 minutes associated with ST segment elevation (STEMI). This generally reflects an acute total occlusion. The therapeutic objective is to achieve rapid, complete, and sustained reperfusion by primary angioplasty or fibrinolytic therapy.

  2. 2. Patients with acute chest pain but without persistent ST-segment elevation. These patients may have persistent or transient ST-segment depression, or T-wave inversion, or no ECG changes. The initial strategy is to relieve ischaemia and symptoms and to monitor the patient with serial ECGs and measurement of biomarkers.

Diagnostic tools

Physical examination

The physical examination is often normal, but is essential to rule out other pathology (pulmonary embolism, aortic dissection, pericarditis, valvular heart disease) and determine the urgency of therapy; if there are signs of concomitant congestive HF, the clinician must expedite management.


A 12-lead ECG must be obtained within 10 min after first medical contact and interpreted immediately by a qualified physician. The typical ECG findings of ischaemia/injury are ST-segment elevation or depression and T-wave inversion in a pattern consistent with the geographic territory of an epicardial coronary artery. However, a normal ECG does not rule out an ACS. In particular, left circumflex artery territory ischaemia or isolated RV ischaemia may be electrically silent in the standard leads. Owing to the waxing and waning nature of myocardial ischaemia/injury, ECG must be obtained within 10 min and repeated at least at 6–9 h and 24 h after presentation.

The diagnosis of STEMI is defined by: ≥1 mm of ST-elevation in two anatomically contiguous leads, new or presumably new left bundle branch block (LBBB), or true posterior MI. The finding of LBBB in the setting of possible ACS is a common cause for delay in reperfusion or treatment due to concern regarding diagnosis and risk of therapy. This is an ideal situation for direct referral to cardiac catheterization when merited.

True posterior infarction is suggested by marked ST-segment depression confined to leads V1 through V4 and accompanied by tall R waves in the right precordial leads and upright T waves.

Localization of ischaemia/infarction

  • I and aVL—high lateral.

  • V5 and V6—lateral.

  • II, III, aVF—inferior.

  • V1, V2, V3, V4—anterior-septal.

Patients with inferior STEMI and haemodynamic compromise should be assessed for ST-segment elevation in right precordial leads to detect RV infarction.


Biomarkers have evolved over time. The latest European Society of Cardiology (ESC) Guidelines suggest that cardiac troponins play the central role in establishing a diagnosis of MI and stratifying risk. In the setting of chest pain, ECG changes, new wall motion abnormalities, or troponin elevation indicates MI. The typical pattern is for troponins to rise 4 h after symptom onset and stay elevated for up to 2 weeks. There is no fundamental clinical difference between troponin T or I. A new addition to the ESC Guidelines is high-sensitive troponins, which have a 10- to 100-fold lower limit of detection. Use of these highly sensitive biomarkers may allow very precise detection of MI within 3 h of presentation, expediting evaluation.


Echocardiography is the most useful modality in the acute care setting as it is widely available, portable, and interpretation is often immediate. The echocardiogram may identify transient subtle wall motion abnormalities during ischaemia or more profound abnormalities during injury. At the same time, echocardiography can help to identify other important causes of chest pain, such as aortic dissection, pulmonary embolism, hypertrophic cardiomyopathy, pericardial effusion, or aortic stenosis. Accordingly, the ESC Guidelines recommend that echocardiography should be routinely available in emergency rooms and chest pain units and used in all patients.

Cardiac magnetic resonance is not yet readily available and is not portable and therefore is not an emergency test. However, cardiac magnetic resonance can assess myocardial function, perfusion, and viability in a single study. This modality is also quite useful to detect myocarditis.

Computed tomography (CT) scans of the coronary arteries may also be used urgently to exclude significant CAD or aortic dissection. These scans may also include the lungs and allow for evaluation of an acute pulmonary embolism.


ACS is divided into STEMI, NSTEMI, and UA. For practical purposes, there are only two broad categories of ACS in terms of treatment: STEMI, which is treated one way, and non-ST elevation ACS (NSTE-ACS), which comprises NSTEMI and UA, which are taken together because they are treated in a similar fashion.

NSTE-ACS is more frequent than STEMI and hospital mortality is higher in STEMI than NSTE-ACS acutely (7% versus 3–5%), but by 6 months mortality is similar (12% and 13%). Long-term follow-up reveals a higher mortality among NSTE-ACS patients. Thus, both conditions must be treated with alacrity.

Differential diagnoses

Several cardiac and non-cardiac conditions can present with symptoms similar to NSTE-ACS. These include myocarditis, pericarditis, cardiomyopathy, valvular disease, Takotsubo cardiomyopathy, aortic dissection, pulmonary embolism, pneumonia, pneumothorax, oesophageal spasm, oesophagitis, peptic ulcer, pancreatitis, cholecystitis, cervical discopathy, zoster, costochondritis, and sickle cell crisis. Echocardiography can rapidly help to separate the cardiac causes from the non-cardiac causes. Once it is determined that patients have NSTE-ACS, it is most appropriate to place them in a dedicated chest pain unit or coronary care unit to expedite and optimize care.

The clinical presentation is highly predictive of early prognosis. Symptoms at rest carry a worse prognosis than symptoms elicited only with exertion. Increasing frequency and duration of symptoms also impacts outcome. Tachycardia, hypotension, or HF on presentation indicate a poor prognosis and should prompt escalation of care.

Risk assessment

The initial ECG predicts early risk. ST depression is worse than T-wave inversion, which is worse than a normal ECG. Also, the number of leads involved and the magnitude of the ST depression in those leads portends greater risk. A unique situation is isolated ST elevation (>1 mV) in lead aVR (often treated as NSTE-ACS because the ST elevation is in only one lead). This is sometimes associated with the very dangerous situation of left main or three-vessel CAD.

Several risk scores have been developed that integrate clinical variables and findings on the ECG with serum cardiac biomarkers. The TIMI (Thrombolysis in Myocardial Ischaemia) risk score is a simple 7-point scale that gives 1 point for age ≥65, ≥3 risk factors, known CAD (>50% stenosis), prior aspirin, ≥2 anginal episodes in previous 24 h, ST deviation ≥0.5 mm of initial ECG, and increased cardiac biomarkers to identify high-risk patients. Patients are considered to be low risk (score of 0–2), intermediate risk (3–4), or high risk (5–7). The composite endpoint of all-cause mortality, MI, and severe recurrent ischaemia at 14 days varies according to the number of TIMI risk factors (score of 0 or 1, 4.7% versus score of 6 or 7, 40.9%). The more complex GRACE risk score, usually calculated online or with a smartphone, provides an even more accurate stratification.

In addition to assessing the risk of cardiac death from ischaemic injury, one must also be concerned with bleeding risk as aggressive anticoagulant therapy is applied to patients with NSTE-ACS. Accordingly, use of the CRUSADE bleeding risk score is recommended by the ESC Guidelines.


Patients with symptoms suggestive of an ACS should be transported rapidly to a hospital by ambulance, if possible. The initial evaluation should be a directed history and physical exam, and an ECG performed within 10 min. Blood should be sent for troponin, Electrolytes, creatinine, and glucose. Patients with elevated troponin or new ST-segment abnormalities should be admitted to a cardiac monitored bed. Patients should be placed at rest with continuous arterial O2 saturation monitoring; only those with saturation <90% or those with pulmonary rales are advised to have supplemental oxygen. A second troponin assay should be performed 3–6 h after the first.

A primary goal of the management of NSTE-ACS is the relief of ischaemic symptoms.

Anti-ischaemic therapy


β‎-Adrenergic receptor blockers have been studied extensively in the setting of STEMI, with data extrapolated to NSTE-ACS. Oral β‎-blockers should be administered within the first 24 h except if the patient has signs of decompensated HF, evidence of low-cardiac output state, increased risk for cardiogenic shock, AV block, asthma, or reactive airway disease. β‎-Blockers can be given to patients with HF once their condition has stabilized.


Nitrates are endothelium-independent vasodilators that increase bloodflow to the myocardium via direct coronary vasodilation. They also reduce myocardial oxygen demand by lowering preload through venodilation and afterload through arterial dilation. Sublingual glyceryl trinitrate may be administered up to three times at 5-min intervals even before the patient arrives at the hospital provided there is no hypotension. Glyceryl trinitrate may be administered as an IV infusion if chest pain persists. Tolerance to the anti-ischaemic effects of nitrates may begin within 24 h and can be avoided by nitrate-free intervals. Hypotension or the recent use of phosphodiesterase (PDE)5 inhibitors are contraindications to nitrate use.


Patients with persistent discomfort despite therapeutic doses of β‎-blockers and nitrates may receive IV boluses of morphine. Morphine acts as an analgesic and anxiolytic and is also a venodilator that reduces preload. Hypotension and respiratory depression are limiting factors.


CCBs are vasodilators that effectively reduce arterial blood pressure. Non-dihydropyridine CCBs such as verapamil and diltiazem also reduce heart rate and myocardial contractility, which reduces demand and can work well as a substitute for β‎-blocker-intolerant patients. Dihydropyridine CCBs such as nifedipine, felodipine, or amlodipine may actually increase heart rate and should generally not be given alone without effective β‎-blockade. The dihydropyridine CCBs may be given safely in the setting of LV dysfunction, but the non-dihydropyridine agents are contraindicated.


Ranolazine inhibits the late sodium current in myocardial cells, which reduces the deleterious effects of intracellular sodium and calcium during ischaemia. Ranolazine has been shown to reduce recurrent ischaemic episodes but not death or MI.

Antiplatelet therapy

The central mechanism in the pathogenesis of thrombotic occlusion of the coronary arteries is platelet activation and aggregation. Accordingly, antiplatelet medication is a cornerstone of the management of ACS.


Acetylsalicylic acid inhibits cyclo-oxygenase-1 (COX-1) and this interrupts the synthesis and release of thromboxane A2 (TxA2), which stimulates platelet aggregation and arterial thrombus formation. The inhibition of COX-1 by aspirin is irreversible, knocking out the platelets for their 7–10-day lifespan. Higher-dose aspirin is not more effective in terms of the hard endpoints of death, MI, or stroke, but is associated with more gastrointestinal bleeding and may precipitate aspirin resistance, leading to reduced efficacy. Thus, guidelines suggest an initial aspirin dose of 162–325 mg followed by daily 75–100 mg.

P2Y12 (adenosine diphosphate) inhibitors

The use of dual antiplatelet therapy (DAPT), including aspirin and a P2Y12 inhibitor, is now routinely advised in the management of ACS. P2Y12 inhibitors are comprised of thienopyridines (ticlopidine, clopidogrel, and prasugrel) and a cyclopentyl triazolopyrimidine (ticagrelor). Thienopyridines irreversibly block the binding of ADP to the P2Y12 receptor on the platelet surface and interfere with both platelet activation and aggregation by adenosine diphosphate (ADP). They require oxidation by the hepatic cytochrome P450 3A4 and 2C19 enzymes to form the active drug. This has important implications in patients with genetic differences in the P450 system, which may result in failure to metabolize the prodrug to its active substrate, with potentially serious consequences for the patient. Conversely, ticagrelor acts directly as a reversible blocker of the P2Y12 receptor and is not affected by cytochrome P450 metabolism.


The CURE trial in patients with NSTE-ACS demonstrated that the addition of clopidogrel (300 mg load followed by 75 mg daily) to standard aspirin therapy in patients with NSTE-ACS reduced cardiovascular death, MI, or stroke by 20%. The benefit was seen within the first 24 h of the dose of clopidogrel and persisted for 1 year. The benefit of clopidogrel was also seen in the group managed with percutaneous coronary intervention (PCI). This and other similar findings revolutionized the way that NSTE-ACS has been managed and resulted in a 1A recommendation for clopidogrel treatment before PCI in the guidelines. Subsequent trials of acute PCI established the loading dose of clopidogrel to be 600 mg followed by 75 mg daily. One issue with giving clopidogrel before PCI is that patients needing to go on to coronary artery bypass graft (CABG) surgery must wait 5 days for bleeding risk to return to acceptable levels. Another issue with clopidogrel is genetic variability of patients to metabolize the prodrug, leading to clopidogrel hyporesponsiveness and potentially serious clinical consequences.


Prasugrel is a thienopyridine that is oxidized to its active metabolite within 30 min at 10 times the level of clopidogrel, resulting in 10-fold greater potency. In the TRITON-TIMI 38 trial patients randomized to prasugrel had a 19% reduction in cardiovascular death, MI, and stroke compared to clopidogrel. This benefit was most notable in patients with diabetes. However, there was more major bleeding in the prasugrel group, especially in patients older than 75 or under 60 kg. In addition, patients with a history of stroke or transient ischaemic attack (TIA) had a prohibitive incidence of intracranial haemorrhage with prasugrel.


Ticagrelor is a novel cyclopentyl triazolopyrimidine oral P2Y12 inhibitor that, unlike the thienopyridines, is reversibly bound. This drug has a more rapid onset of platelet inhibition than clopidogrel and also a more rapid offset. Like prasugrel, this drug provides almost complete P2Y12-mediated platelet aggregation inhibition. The PLATO trial compared ticagrelor with clopidogrel in moderate-to-high risk NSTE-ACS patients or STEMI patients planned for primary PCI. The primary endpoint, a composite of cardiovascular death, MI, and stroke, fell by 16% in the ticagrelor group, across a broad array of subgroups. Interestingly, PLATO showed no benefit of ticagrelor in patients enrolled in the USA, where the aspirin dose was more often 325 mg as opposed to lower doses outside the USA. Accordingly, the Food and Drug Administration recommended that ticagrelor only be used with low-dose aspirin (75–100 mg). The success of ticagrelor was also moderated by a 0.7% higher incidence of non-CABG-related major bleeding, although it reduced early and late mortality after CABG. Some patients may develop dyspnoea after ticagrelor that is idiosyncratic and not related to congestive HF (Box 19.2).

Source data from European Heart Journal, 37, 3, Roffi M., Patrono C., Collet JP., 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Oxford University Press 2016.

Withdrawal of DAPT

Interruption of DAPT soon after stent implantation increases the risk of acute stent thrombosis, with up to 45% mortality at 1 month. If interruption of DAPT becomes mandatory owing to major bleeding, there is no proven alternative therapy. Most surgical procedures can be performed without interrupting DAPT or at least while continuing aspirin alone. In all cases, the risk of bleeding related to surgery must be weighed against the risk of ischaemic events off DAPT. If DAPT must be stopped for surgery, then clopidogrel and ticagrelor are held for 5 days, while prasugrel requires 7 days.

Lipid-lowering therapy

Multiple clinical trials have confirmed the morbidity and mortality benefit of early use of HMG CoA reductase inhibitior therapy (statin) in patients with ACS. Thus, all guidelines recommend that an essential element of the medical management of all patients with NSTE-ACS or acute MI is the immediate institution of high-dose statin therapy.

Invasive versus conservative management

There are two general approaches to the timing of cardiac catheterization and revascularization in patients with NSTE-ACS: an early invasive strategy involving routine cardiac catheterization within 48 h followed by revascularization or a more conservative approach with initial medical therapy followed by catheterization only if there is spontaneous recurrent ischaemia or ischaemia provoked by a non-invasive stress test. The early invasive strategy has been shown to result in a 25% reduction in mortality and a 17% reduction in non-fatal MI at 2 years of follow-up, a benefit that is more prominent in high-risk patients. As a result, the ESC Guideline recommends an early invasive strategy for patients with NSTE-ACS accompanied by ST-segment changes and/or positive troponin on admission or in those who develop high-risk features over the subsequent 24 h.


Heparin interferes with thrombin formation and is given by bolus (60 U/kg IV, maximum 5000 U) and infusion (12 U/kg/h, maximum 1000 U/h) adjusted to maintain a partial thromboplastin time between 50 and 70 s. Low-molecular weight heparin is preferred by many physicians because of a lower incidence of heparin-induced thrombocytopenia, ease of administration without need for monitoring, and a lesser degree of platelet activation.

Direct thrombin inhibitors

Direct thrombin inhibitors, which include bivalirudin, lepirudin, and hirudin, are another alternative to UFH. Bivalirudin compared to UFH was associated with significantly less bleeding in the ACUITY and REPLACE-2 trials with similar ischaemic outcomes.



Sublingual glyceryl trinitrate (GTN) is administered to patients presenting with chest pain, followed by IV GTN for hypertension, HF, or chest pain that persists after three sublingual GTN tablets. Caution must be observed in severe RV infarction, severe aortic stenosis, or patients who have taken PDE inhibitors for erectile dysfunction within the previous 24 h.


Multiple controlled trials have demonstrated the efficacy of β‎-blockers in acute MI. Although no randomized trials specifically address β‎-blockers in UA and NSTEMI, they are recommended.

Adjunctive medical therapy

Lipid-lowering therapy (statins)

A mortality benefit of atorvastatin 80 mg daily was demonstrated in the PROVE-IT TIMI 22 and MIRACL trials. Initial intensive statin therapy, rather than gradual uptitration, is recommended because of demonstration of benefit in the first 30 days.

ACE inhibitors/ARBs

Oral ACE inhibitors should be administered within the first 24 h of MI onset in patients with an anterior STEMI, HF, or LVEF ≤40%. This class of drugs reduces mortality in patients with MI, as demonstrated in ISIS-4 (captopril) and GISSI-3 (lisinopril). These drugs should not be administered intravenously in the first 24 h or in patients with hypotension (SBP <100 mmHg).

ARBs (valsartan and candesartan) are generally reserved for patients intolerant of ACE inhibitors. ARBs were as effective as ACE inhibitors in the immediate post-MI setting in the VALIANT study, but the combination of the two demonstrated an increased incidence of adverse effects without improving survival.

Aldosterone antagonists

Eplerenone, an aldosterone antagonist, when given to patients with an LVEF ≤40% and symptomatic HF or diabetes along with ACE inhibitors and standard therapy in the EPHESUS trial, reduced mortality significantly at 30 days (3.2% versus 4.6% with standard care).



The diagnosis of STEMI requires clinical symptoms of ischaemia, ST-segment elevation in at least two contiguous leads, and elevated troponin. The clinical symptoms may be much broader than chest pressure and may include nausea/vomiting, shortness of breath, fatigue, palpitations, or syncope; up to 30% of STEMI presentations are atypical symptoms. Echocardiography is indicated when the diagnosis of acute MI is uncertain.

Initial evaluation in the emergency department

Initial evaluation in the emergency department should include a 12-lead ECG within 10 min of first medical contact, continuous ECG monitoring, and blood sampling for troponin (T or I) immediately on presentation with repeat in 3 h. In the proper clinical scenario with ongoing chest discomfort and ST-segment elevation, initiation of reperfusion therapy should not be delayed while awaiting troponin results. Echocardiography may be useful to assist in the diagnosis in uncertain cases.

Special considerations: the ECG diagnosis of acute MI is difficult in the presence of LBBB. New LBBB in the proper clinical scenario, however, should prompt urgent reperfusion therapy.

Prehospital care

Emergency medical service response optimally includes performance and interpretation of a 12-lead ECG. Once ST-segment elevation or a new LBBB is identified, it would be appropriate to transport the patient to a centre capable of performing primary PCI within 90 min (preferably within 60 min) of presentation. If the patient presents to a hospital that is not PCI-capable, but PCI may be performed within 120 min from presentation, then transfer for primary PCI is still appropriate. If time to PCI is more than 120 min, then immediate fibrinolysis should be administered prior to transfer to a PCI-capable centre.

Reperfusion strategy

Reperfusion therapy is indicated in all patients with symptoms of less than 12 h duration and persistent ST-segment elevation or new LBBB or even later if there is evidence of ongoing ischaemia (class I recommendation). Reperfusion therapy with primary PCI may be considered in stable patients presenting 12–24 h after symptom onset but this is a class IIb recommendation. Routine PCI of a totally occluded artery more than 24 h after symptom onset in a stable patient without signs of ischaemia is not recommended.

Primary PCI

Primary PCI is preferred over fibrinolysis if performed by an experienced team within 120 min of first medical contact (class I recommendation). Primary PCI in patients with severe acute HF or cardiogenic shock is also a class I recommendation. Radial access is preferred over femoral access and drug-eluting stents are preferred over bare metal stents in the absence of contraindications (class IIa recommendation). Treating other significant stenoses via PCI at the same time as the infarct-related artery in patients with multivessel disease may be considered (class IIb).

Periprocedural pharmacotherapy

Antiplatelet therapy

Class I recommendations include aspirin and either prasugrel (unless there is prior stroke/TIA or age >75), ticagrelor, or clopidogrel, all with a loading dose. Glycoprotein IIb/IIIa inhibitors may be added if there is angiographic evidence of massive thrombus or no reflow (class IIa).

Anticoagulant therapy

An injectable anticoagulant is indicated in all patients with primary PCI (class I), either heparin, enoxaparin, or bivalirudin. Enoxaparin may be preferable to UFH (class IIb). Bivalirudin is preferred to UFH with a GP IIb/IIIa inhibitor (class I). Fondaparinux is not recommended for primary PCI (class III). Use of fibrinolysis before planned PCI is not recommended (class III).


Fibrinolytic therapy is recommended within 12 h of symptom onset if primary PCI cannot be performed within 120 min of first medical contact, preferably with a fibrin-specific agent such as tenecteplase, alteplase, or reteplase (class I). Initiation in the prehospital setting is preferred (class IIa). Adjunctive therapy includes aspirin, clopidogrel, and anticoagulation with weight-based enoxaparin or heparin. Transfer to a PCI-capable centre is indicated for all patients following fibrinolysis (class I). In patients with HF, shock, failed thrombolysis, or evidence of recurrent ischaemia, urgent angiography and PCI are indicated (class I). Elective angiography with a view to revascularization of the infarct-related artery is indicated after successful fibrinolysis (class I) 3–24 h (class IIA).

Long-term therapies

Lifestyle interventions and risk factor control are mandatory, including formal protocols for smoking cessation and diet and weight control. Blood pressure control is essential and appropriate drug therapy may be required. Exercise-based cardiac rehabilitation has been shown to be effective at reducing all-cause mortality and the risk of reinfarction as well as improving risk factors. Stress management may be useful as well.

The timing of resumption of normal daily activities must be individualized, based on LV function, completeness of revascularization, and rhythm control. Physical activity after discharge should be encouraged with gradual progression.

Aspirin has established benefits and should be used indefinitely in all patients with STEMI, generally at low doses (70–100 mg). Patients intolerant to aspirin can receive clopidogrel 75 mg per day as long-term secondary prevention. DAPT is recommended in patients with STEMI for up to 12 months. Oral treatment with β‎-blockers is indicated in patients with HF or LV dysfunction. The routine use of nitrates is of no benefit. CCBs are not given routinely, but may be substituted in patients in need of heart rate slowing and with contraindications to β‎-blockers as long as there is no HF or impaired LV function. ACE inhibitors should be given to all patients with an impaired EF (<40%) or who have signs and symptoms of HF. ARBs are an alternative in patients not able to tolerate an ACE inhibitor. Aldosterone antagonists should be considered for post-STEMI patients with EF <40% and HF or diabetes, provided that creatinine is not elevated (<221 µmol/l in men and <177 µmol/l in women) and potassium is <5.0 mEq/l. Finally, the benefits of statin therapy in secondary prevention have been demonstrated unequivocally, and high-dose statins must be started in the hospital and continued indefinitely after discharge in all patients with acute MI irrespective of cholesterol concentration. Lipids should be re-evaluated 4–6 weeks after the MI to evaluate efficacy.

Cardiac complications

Disorders of heart rhythm

Arrhythmias after MI include new-onset AF, non-sustained VT, high-degree AV block, sinus bradycardia, sinus arrest, sustained VT, and VF.

Immediate electrical cardioversion for AF is indicated when there is haemodynamic compromise or HF. Intravenous β‎-blockers or non-dihydropyridine CCBs are indicated for rate control if there are no clinical signs of acute HF. IV amiodarone is indicated in case of rapid ventricular response in the presence of concomitant acute HF or hypotension. Patients with AF and risk factors for thromboembolism should be adequately treated with oral anticoagulation. In patients with STEMI and with AF requiring permanent anticoagulation, triple therapy combining aspirin, an ADP receptor antagonist, and an oral anticoagulant is recommended to reduce the burden of thromboembolic complications associated with AF and to minimize the risk of stent thrombosis. However, this does come with the risk of increased bleeding complications.

VT and VF should be treated with direct current cardioversion (class I). Electrolyte disturbances must be corrected and IV magnesium considered. Polymorphic VT should be treated with IV β‎-blockers or IV amiodarone, and urgent angiography considered to rule out ischaemia. Sustained monomorphic VT that is recurrent should be treated with IV amiodarone. Assessment of LV function is a key component of risk evaluation for sudden cardiac death; ICD as primary prevention should be considered if EF <40%, but only 40 days after the acute event).

Structural issues after STEMI

Rupture of the LV free wall may occur during the subacute phase of recovery from transmural infarction. This may present with sudden pain and cardiovascular collapse, and is typically associated with haemopericardium and tamponade. Once recognized, the treatment is immediate surgery.

Ventricular septal rupture may also occur several days after the acute MI. This typically presents with rapid onset of HF and a new loud systolic murmur. An intra-aortic balloon pump may stabilize patients in preparation for surgery. The timing of surgery is controversial but is probably best done early. Mortality remains high in all patients and is particularly high in those with inferobasal defects as opposed to anteroapical defects.

RV infarction may occur in isolation but is typically seen in the presence of an inferior wall STEMI. The classic triad of hypotension, clear lung fields, and elevated jugular venous pressure should suggest this diagnosis. ST-segment elevation right-sided leads should be routinely sought in patients with inferior STEMI and hypotension. The management of RV infarction is to maintain RV filling pressure, and so diuretics and vasodilators should be avoided.

The incidence of pericarditis after STEMI has decreased in recent years with aggressive early reperfusion therapy. A pericardial rub will confirm the diagnosis but may be absent if there is a substantial pericardial effusion. Echocardiography is particularly helpful in establishing this diagnosis. The pain usually responds to colchicine. Steroids should be avoided owing to the risk of scar thinning and rupture. When pericardial effusion is present, anticoagulant therapy should be avoided.

Large transmural infarctions of the anterolateral wall may undergo infarct expansion and development of LV aneurysm. ACE inhibitors, ARBs, and aldosterone antagonists have been shown to reduce the remodelling process in transmural infarction. Echocardiography is helpful to make this diagnosis and also to exclude apical mural thrombus. Mural LV thrombus, once diagnosed, requires oral anticoagulation. The optimal duration of therapy is not known; repeat echocardiography to document resolution may provide guidance in this respect.

Acute heart failure: assessment


Heart failure (HF) is defined as a failure to deliver oxygen at a sufficient rate to match the requirements of metabolizing tissues despite normal filling pressures, secondary to an abnormality in underlying cardiac structure or function. Acute heart failure (AHF) is the rapid onset or change in HF signs and symptoms resulting in the need for urgent therapy.

Epidemiology and incidence

Over 67 000 hospital admissions in England and Wales per year are due to AHF. It is a leading cause for hospitalization in patients greater than 65 years old in the UK. It carries huge morbidity and mortality burdens. A single hospital admission due to AHF, in itself, is an indicator of poor prognosis, with the risk of further hospital admissions being as high as 50% over 6 months and mortality up to 40% over 1 year. Its incidence increases with age, and at 75 years and older, this incidence increases more steeply.

HF aetiologies

HF can occur because of cardiac dysfunction from impaired systolic function (HF with reduced EF [HF REF]). In an approximately equal proportion of patients it can be due to a disorder of diastolic function with preserved systolic function (HF with preserved EF [HF PEF]). Frequently, patients can have both systolic and diastolic impairment.

HF with systolic impairment is the better understood form with regard to its pathophysiology, with two-thirds of cases due to underlying CAD. There are many other causes of cardiomyopathy, e.g. viral myocarditis, alcohol, peripartum, and idiopathic dilated cardiomyopathy.

Patients with HF PEF tend to be older, female patients. Patients with this form of HF are less likely to have significant CAD but more likely to have hypertension and AF. The prognosis of HF PEF is better than HF REF.

The Acute Decompensated Heart Failure National Registry (ADHERE) showed that the major reasons for HF hospitalizations in the USA are worsening chronic HF (70%), de novo AHF (25%) and advanced/end-stage HF (5%). In the majority of cases AHF occurs in patients with pre-existing chronic HF and is triggered by a clear precipitant, e.g. an ACS, arrhythmia, or discontinuation of diuretics in HF REF and severe hypertension or volume overload in HF PEF. AHF can also be the first presentation (‘de novo’ HF).

History and examination

HF symptoms and signs are usually dominated by those related to congestion because of elevated filling pressures. High left-sided filling pressures cause lung congestion, noticeable as dyspnoea, orthopnoea or paroxysmal nocturnal dyspnoea, lung rales, noticeable S3, or loud P2. Presence of an S3 is an adverse prognostic sign. Auscultation for murmurs may detect important underlying valvular disease.

Elevated right-sided filling pressures cause anorexia, early satiety, abdominal fullness, discomfort when bending, and high jugular venous pressure (JVP), oedema in pending regions, or ascites, related to venous congestion in the liver, kidney, intestine, jugular veins, or lower extremities.

Symptoms and signs attributable to low resting cardiac output are less common and usually include prostration or fatigue, low blood pressure, narrow pulse pressure, ACE inhibitor-related symptomatic hypotension, cold extremities, sleepiness, pulsus alternans, or low urine output. Usually, low resting cardiac output symptoms appear in an advanced stage of chronic HF.

Approach to assessment

Does this patient have HF?

The diagnosis of AHF is based on the symptoms and clinical findings, supported by appropriate investigations, such as ECG, CXR, biomarkers, and Doppler echocardiography.

Up to 75% of AHF patients will have a previous diagnosis of HF at presentation and the available information may help the clinician. Dyspnoea is a common presenting symptom in patients with AHF syndromes.

Dyspnoea is the primary reason that patients present for medical care with AHF. In the ADHERE (n = 163 447) and OPTIMIZE-HF (n = 48 612) registries, 89% and 90% of patients, respectively, initially presented with a complaint of dyspnoea.

Dyspnoea on exertion is the most sensitive symptom (negative likelihood ratio 0.45, 95% confidence interval [CI] 0.35–0.67), whereas paroxysmal nocturnal dyspnoea is the most specific (positive likelihood ratio 2.6, 95% CI 1.5–4.5). Elevated JVP is the best indicator for identifying acute decompensated HF (positive likelihood ratio 5.1, 95% CI 3.2–7.9, negative likelihood ratio 0.66, 95% CI 0.57–0.77), although measurement of JVP by clinicians is notoriously inaccurate. A murmur may point to a new valvular disease or a complication of a previously known heart disease. An auscultated S3 gallop is not only diagnostic for AHF but predicts an increased risk of subsequent adverse events. Both ventricular gallops and jugular venous distension are limited by interobserver variation and low sensitivity.

In the emergency department, rapid measurement of brain natriuretic peptide (BNP) or N-terminal (NT)-proBNP used in conjunction with other clinical information is useful in establishing or excluding the diagnosis of congestive HF in patients with acute dyspnoea, and improves the evaluation and treatment of patients with acute dyspnoea, thereby reducing the time to discharge and the total cost of treatment.

Although the pulmonary artery catheter (PAC) may provide a good measure of filling pressures and an estimate of cardiac output in the patient in shock, therapy to reduce volume overload during hospitalization for HF led to marked improvement in signs and symptoms of elevated filling pressures with or without the PAC. Addition of the PAC to careful clinical assessment increased anticipated adverse events, but did not affect overall mortality and hospitalization.

What is the aetiology?

The HF aetiology is the next question to answer as it may imply specific management (Table 19.4).

Table 19.4 Precipitants of AHF need to be recognized

Precipitants of rapid decompensation

Precipitants of slower decompensation


Non-compliance with diuretics or fluid restriction.

Complications of ACS, e.g. ruptured interventricular septum or papillary muscle/chordae of mitral valve


RV infarction


Tachyarrhythmias or severe bradycardia and conduction disease

Worsening pre-existing valvular dysfunction

Pulmonary embolism

Severe thyroid dysfunction

Cardiac tamponade

Exacerbation of lung disease, e.g. chronic obstructive pulmonary disease

Aortic dissection

Renal failure

Hypertensive crisis


Peripartum cardiomyopathy

Iatrogenic, e.g. NSAIDS/steroids

Are there any precipitating factors?

The presence of any precipitating factors should be sought as correction may be of most importance to stabilize the patient, such as a hypertensive emergency, anaemia, dysrhythmia, or infection.

Are there other conditions/comorbidities that may contribute to the picture?

Patients with AHF also have significant cardiac and non-cardiac underlying conditions that may not be the main aetiology but may contribute to the pathogenesis of AHF, including CAD (ischaemia, hibernating myocardium, and endothelial dysfunction), hypertension, AF, and type II diabetes mellitus. Many patients have other complications of atherosclerosis, hypertension, or diabetes, while other conditions share a common aetiology, such as smoking-related chronic pulmonary disease or renal vascular disease. Some comorbidities are complications of HF or the combination of HF, its underlying aetiology and advanced age, such as renal impairment, stroke, and atrial and ventricular arrhythmias. Patients with renal failure are less likely to be prescribed efficacious therapies, but have better outcomes if they receive these medications.

The importance of certain comorbidities as independent predictors of poor outcome showed the importance of considering them as potential therapeutic targets, such as anaemia or obstructive sleep apnoea.

Troponins, worsening renal function, hyponatremia lung congestion persistence after initial treatment, and low SBP have all been described as the main prognostic factors in AHF.

Systolic dysfunction or preserved EF?

Patients should be classified as soon as possible according to previously described criteria for systolic and/or preserved dysfunction, and by the characteristics of left or right HF.



Besides signs of heart disease, the ECG may provide important aetiological information such as ACS or rhythm disturbances. If a patient presents acutely with suspected ‘HF’ with an entirely normal ECG, the likelihood of them having actual HF as the diagnosis is low (<2%). A normal ECG has less of a negative predictive value in patients with suspected chronic HF.


Although chest radiography is routine in the evaluation of patients with shortness of breath and a quick and inexpensive examination, ~1 of every 5 patients admitted from the emergency department with AHF has no signs of congestion on chest radiography, and patients lacking signs of congestion on emergency department chest radiography were more likely to have an emergency department non-HF diagnosis than patients with signs of congestion in the ADHERE registry.

Cardiac peptides

When the heart muscle cell is stretched, as in HF, cardiac myocytes release the precursor 108-amino acid peptide proBNP. This is further cleaved into BNP and the amino terminal NT-proBNP, which are both released into the bloodstream. The severity of disease and prognosis correlates with the level of BNP/NT-proBNP detected. The higher the level, the worse the HF.

Taken together with clinical information, BNP/NT-proBNP are quantitative markers of HF that summarize systolic and diastolic LV dysfunction, as well as valvular heart disease and RV dysfunction. In particular, they can support clinical judgement in cases when the diagnosis is uncertain. The knowledge of a patient’s baseline BNP/NT-proBNP level prior to hospital admission can help to compare disease severity between admissions.

Either BNP or NT-proBNP can be measured, as long as their cut-off values are not used interchangeably. When using cut-off values in patients with suspected HF, a BNP value of <100 pg/ml or NT-proBNP <300 pg/ml can rule out HF (ESC guidelines 2013/National Institute for Health and Care Excellence [NICE] guidelines 2015). There seems to be a linear relationship between body mass index and BNP. Patients who are obese or very obese should have their BNP multiplied by 2.0 to obtain a BNP level of similar severity to those of normal weight. BNP levels in the dyspnoeic patient do not have to be adjusted for age or gender. However, to optimize diagnostic accuracy, adjustments should be made for renal dysfunction and obesity.

One should not forget that both BNP and NT-proBNP blood levels are markers of heart muscle cell stretch, and there may be causes other than HF to justify their increased levels, either of cardiac origin, as in ACS, hypertension, LV hypertrophy, or valvular heart disease, or of non-cardiac origin, such as pulmonary embolism, pulmonary hypertension, or sepsis.

Cardiac troponin T or I

Given that ACS can precipitate AHF, the measurement of troponin T or I in this setting is recommended in the American College of Cardiology/American Heart Association 2013 guidelines. Although it is important to take into consideration that frequently troponin can be elevated in patients without underlying significant coronary disease, indicating that ongoing myocardial injury occurring in HF alone is suggestive of worse prognosis.

Blood gas analysis, electrolytes, renal function, and routine haematology

Pulse oximetry is a valuable option for immediate evaluation of oxygenation, but if the patient presents with signs of compromised peripheral perfusion or fatigue, blood gas analysis is useful to evaluate acid–base and lactate status and to follow the response to treatment. Electrolyte abnormal values are often associated with rhythm disturbances, may be the result of abnormal renal function or drug administration, and are often administered to compensate the use of some drugs. Anaemia is a common precipitating cause and AHF may just be the symptom translation of anaemia that may benefit from treatment.


When it comes to HF, clinical examination alone may be an inaccurate diagnostic approach. Ultrasound examination of the heart, echocardiography, is widely accepted as an objective diagnostic tool in characterizing cardiac dysfunction. Besides ventricular function, evaluation echocardiography may provide early aetiological information, such as ischaemic regional motion abnormalities that cannot yet be seen in the ECG, signs of muscular, valvular, or pericardial disease. It should be done in every patient as soon as possible. Limited emergency echocardiography to evaluate wall motion and EF performed by emergency physicians has been shown to correlate well with definitive testing.

Other investigations

Patients with ACS or serious mechanical cardiac disorders should proceed rapidly to angiography and catheterization for evaluation and therapeutic measures, including surgery or PCI.

Acute heart failure: management


AHF is defined as gradual or rapid change in HF signs and symptoms, resulting in a need for urgent therapy. The vast majority of patients present with dyspnoea, owing to increased LV filling pressures, with or without low cardiac output, with reduced or preserved EF. This is a potentially life-threatening condition and usually leads to urgent admission. Most cases occur in patients known to have HF, although it can be a first presentation.

Until recently, the clinical characteristics, management patterns, and outcomes of patients admitted with AHF have been poorly defined owing to lack of specific data. AHF syndromes have traditionally been viewed as part of the chronic HF natural evolution, and lung congestion is often regarded as a consequence of volume overload and/or low cardiac output, usually precipitated by arrhythmias, ACS, dietary indiscretion, and/or medication non-adherence (or withdrawal), but several large AHF registries shed new light on the way we see and manage AHF.

Yet, admission SBP has been shown to be an independent predictor of morbidity and mortality in patients with AHF with either reduced or relatively preserved systolic function. Patients with high SBP were more likely to have preserved systolic function, while patients with low SBP at admission had 3–4 times higher in-hospital and postdischarge mortality rates. Low SBP (<120 mmHg) at hospital admission identifies patients who have a poor prognosis despite medical therapy. This is a marker of advanced HF in a patient who usually has a history of cardiac disease, shows peripheral oedema, enlarged liver, decreased renal and liver function, and hyponatraemia.

The problem: increased intracardiac diastolic pressure and oxygen disrupted balance

The heart pumping function maintains low intracardiac diastolic pressures, allowing systemic and pulmonary venous return. Increased LV diastolic pressures lead to pulmonary congestion and poorer oxygenation. Increased RV diastolic pressures lead to peripheral oedema, liver, kidney, and mesenteric vein increased pressures, with decreased function in these organs. Because they share a common septum, increased pressures in one side of the heart push the septum, increasing pressure and decreasing diastolic volume in the other side, further compromising stroke volume and cardiac output. This is particularly important with hypoxia consequent to lung congestion, which may markedly increase PVR, causing an increase in RV end-diastolic pressure that will further contribute to increased LV end-diastolic pressure and decreased LV diastolic volume. If there is deterioration in ventricular filling, as in HF with preserved EF, pressure is increased from the beginning of diastole. If the systolic function is compromised, the heart will try to maintain its output at the cost of increased diastolic ventricular volume, and the pressure goes up.

Increased intracardiac diastolic pressure increases wall tension, decreasing at the same time coronary bloodflow when the oxygen consumption is greater. In the AHF patient with lung congestion, this becomes more noticeable because of poorer blood oxygenation, and, in each episode, the heart oxygen balance is further compromised by decreased myocardial perfusion owing to increased diastolic pressures, increased heart rate, or arrhythmia, with further impairment of cardiac contractility, enhancing the process of pulmonary congestion, thus contributing to ongoing irrevocable myocardial damage. In the later stage of chronic HF, where low cardiac output is more prevalent, low BP adds a critical component, especially in patients with CAD, aggravating myocardial perfusion. In each episode, the bigger the oxygenation compromise, the bigger the hypotension, the greater the myocardial damage that will happen.

New arrhythmia during an exacerbation of HF identifies a high-risk group with higher in-hospital and 60-day morbidity and mortality. Thus, each episode of AHF contributes more myocardial damage and worsens long-term prognosis.

AHF initial management

Goals for AHF patient management

  • Immediate—improve symptoms:

    • Restore oxygenation and improve organ perfusion

    • Avoid or limit cardiac, renal, and other organ damage.

  • Intermediate—stabilize patient and optimize treatment:

    • Initiate life-saving therapies.

  • Long-term—disease management:

    • Prevent early readmission

    • Improve symptoms and survival.

As in other medical emergencies, AHF needs a rapid, initial integrative approach where assessment and management are provided in the shortest time.

Pharmacological treatment

  • Oxygen should be given in hypoxic patients only (e.g. SpO2 <90% or <8.0 kPa). Routine administration in non-hypoxic patients with LV systolic dysfunction can cause unfavourable haemodynamic effects through oxygen-mediated systemic vasoconstriction via several complex mechanisms and reduction in cardiac output by heart rate reduction as demonstrated by a large randomized controlled trial by Park et al. in 2010.

  • Loop diuretics: patients with pulmonary oedema have rapid symptomatic relief with loop diuretics, not just because of the diuretic effect but also owing to their rapid vasodilator action. Higher doses of diuretics result in more rapid symptom improvement, but with greater risk of renal dysfunction. A large randomized controlled trial comparing twice-daily IV bolus administration of loop diuretics versus continuous infusion has shown no difference with respect to symptoms or changes in renal function.

  • Thiazide diuretics: thiazide or thiazide-like diuretics, e.g. metolazone, may need to be used to treat resistant oedema. Risk of renal dysfunction from a combination of these agents means that they should only be used as a short-term measure.

  • Opiates: these potentially have benefits because of their anxiolytic and vasodilator effect; however, they increase the risk of respiratory depression and the possible need for ventilator support (non-invasive or invasive). Opiates should not be offered routinely and should be limited to cases of respiratory distress and anxiety.

Subsequent management for patients with AHF is guided by these haemodynamic parameters

  • Systolic BP >110 mmHg: consideration of vasodilator therapy, e.g. with intravenous nitrate, can help to reduce preload and afterload, thereby increasing stroke volume. It should be avoided in patients with severe aortic stenosis, mitral stenosis, or hypertrophic cardiomyopathy with severe outflow tract obstruction.

  • • Nesiritide (a human BNP) has recently been shown to have a small effect in reducing dyspnoea when added to standard therapy.

  • Systolic BP <85 mmHg: in patients with shock, non-vasodilating inotropes can be considered, e.g. dobutamine. In the patient who is not shocked, inotropes are not recommended. The sinus tachycardia associated with many of these agents increases myocardial oxygen demand (and potentially ischaemia), and there is increased risk of atrial tachyarrhythmias and VT.

Inotropes used in AHF

Dobutamine is a positive inotrope that works by being an agonist to β‎-adrenergic receptors and in turn increasing cAMP and calcium influx into cardiac myocytes. Its β‎2-adrenergic activity also means that it can have mild vasodilator effects. Usually an infusion at a starting dose of 2.5 µg/kg/min may be required.

Milrinone is a PDE inhibitor that prevents the degradation of cAMP. The build-up of cAMP increases the influx of calcium into the cardiac myocytes, thereby increasing myocardial contractility. Milrinone causes a greater degree of peripheral vasodilation than dobutamine. Therefore, the choice of inotrope here depends on a balance between increased heart rate and contractility, hence the greater myocardial oxygen demand related to dobutamine versus the hypotension likely to be associated with milrinone. Dobutamine is often the first-line inotrope used in acute decompensation with low systolic BP.

Levosimendan is a positive inotrope. It increases cardiac contractility by sensitizing troponin C to calcium. Unlike dobutamine and milrinone it does not increase intracellular calcium or cAMP and is therefore thought to have fewer cardiotoxic effects potentiated by high concentrations of intracellular calcium and so better long-term mortality. However, in the SURVIVE trial (Survival of Patients with Acute Heart Failure in Need of Intravenous Inotropic Support), there was no overall difference in all-cause mortality between levosimendan and dobutamine apart from in the subgroup of patients that had pre-existing chronic HF on long-term β‎-blockers. Levosimendan outperformed dobutamine in this category. The action of levosimendan is not attenuated by concomitant β‎-blockers (β‎-blockers are cardioprotective and well established in HF guidelines), unlike the β‎-agonistic actions of dobutamine. For this reason, it is recommended by ESC guidelines as an option in patients with congestive heart failure on β‎-blockers.

Levosimendan also has vasodilator effects that are mediated by ATP-dependent opening of potassium channels that can be profound and therefore should be avoided in patients with SBP <85 mmHg.

If no improvement after subsequent re-assessment?

  • Normotensive and urine output <30 ml/h: increasing the diuretic dose may encourage diuresis in the first instance. Venovenous ultrafiltration is the process of extracorporeal extraction of solute and water from whole blood and can be performed through either central or peripheral vascular access. It allows for the rapid and controlled removal of fluid and may be considered in patients when large-dose loop diuretics and dopamine fail to achieve effective diuresis.

  • SBP <85 mmHg and evidence of end-organ hypoperfusion despite inotropes: mechanical support such as with intra-aortic balloon pump may need to be considered as a bridge to definitive correction of mechanical problems (such as acute mitral regurgitation/ventriculoseptal defect). Occasionally, they are used as a bridge to ventricular assist device or transplant. They should not be inserted unless there is a clear exit strategy. Other methods of mechanical support that may be used to bridge for transplant or bridge to decision for transplant are the Impella percutaneous ventricular assist device or venoarterial extracorporeal membrane oxygenation.

  • Persistent hypoxia and respiratory distress: consideration of non-invasive positive pressure ventilation or continuous positive airway pressure may reduce afterload and improve symptoms and oxygen saturation, although studies suggest that mortality and intubation rates are not changed. If the respiratory acidosis is associated with mental status changes, endotracheal intubation and mechanical ventilation should be considered, as non-invasive ventilation needs patient cooperation. Signs of poor organ perfusion should be addressed immediately as in any acute circulatory failure.


Noradrenaline or adrenaline cause peripheral vasoconstriction and have inotropic effects. Their use in AHF should be limited to patients who are profoundly hypotensive despite adequate filling pressures. They can worsen left ventricle performance by increasing the afterload and have similar adverse effects to inotropes.

The immediate priority in AHF patients should be the stabilization of the respiratory failure to restore oxygenation and prevent further deterioration. The initial therapy for patients with AHF should improve symptoms and haemodynamics without causing myocardial injury that may adversely affect postdischarge morbidity and mortality. Several common therapies, such as loop diuretics, morphine, inotropes, or inodilators, have long been used as first-line therapy without sound evidence from randomized studies on their benefit on morbidity or survival. However, all patients are not created equal and, in euvolaemic or hypovolaemic patients, loop diuretics may induce marked decreases in stroke volume and cardiac output, hypotension, or worsening renal function, while inodilators used in patients with preserved systolic function may increase mortality and hospital stay.

Several therapies in AHF management have an unacceptably high incidence of hypotension that may per se increase cardiac, renal, and other organ damage. Their use should require frequent, or preferably, continuous BP monitoring and pre-emptive measures to avoid it.

Specific situations


AF is the most common tachyarrhythmia encountered in HF. It can precipitate AHF. If the patient is compromised, e.g. with pulmonary oedema or profound haemodynamic instability, emergency cardioversion should be considered.

In patients who are more stable, it has been proven in several large trials that rhythm control strategy is not superior to rate control strategy. In HF, β‎-blockers are the preferred first-line agent for rate control for AF rather than digoxin (as this does not control heart rate in exercise), and also for their dual benefit on long-term mortality. However, in AHF, β‎-blockers should only be started once the patient has been stabilized (usually when they are switched to oral diuretics). Therefore, patients with acute HF REF with fast AF may need rate control with either digoxin or amiodarone instead until they are stabilized. Patients who were on β‎-blockers before their acute decompensation can continue to take them.

In HF PEF, a rate-limiting CCB, e.g. verapamil, can be used, in combination with digoxin if resistant to treatment.

VT can also frequently occur in HF, particularly with HF REF, and is associated with poor outcomes. VT with haemodynamic compromise should be treated as per the ALS (Advanced Life Support) algorithm with emergency DC cardioversion, and amiodarone should be administered. Potential aggravating factors such as deranged electrolytes and myocardial ischaemia should be investigated and treated. Patients with a suspicion of underlying CAD should undergo invasive coronary angiography once stabilized. ICD implantation may need to be considered prior to discharge once the patient is optimized.

In patients with pre-existing HF with an ICD already in situ that is repetitively firing due to VT, ICD reprogramming and amiodarone administration is recommended. Catheter ablation may need to be considered for VT storms resistant to treatment.

Severe bradycardia and high-degree AV block can also precipitate AHF, in which case emergency pacing is recommended.


Emergency primary PCI is recommended in patients who have ST elevation or new LBBB. Urgent revascularization is recommended for patients with NSTEMI. In select cases following an angiogram, a CABG may be necessary.

Isolated RV infarction

Acute RV infarction can occur as a result of an ACS owing to an obstructed right coronary artery or a dominant left circumflex artery. It can also occur following a massive pulmonary embolism. It is characterized by raised right-sided filling pressures and severe tricuspid regurgitation and reduced cardiac output. Therefore, caution must be taken with furosemide or vasodilators that may further reduce cardiac output.

Valvular problems may cause AHF. The low cardiac output state with HF REF makes the echographic assessment for severity of these lesions challenging.

Approximately 7% of AHF is caused by aortic stenosis. Severity of aortic stenosis on echo may be underestimated when measuring peak gradients in patients with reduced EF and cardiac output (low-flow, low-gradient aortic stenosis). This may lead to further interrogation of the valve with a stress echocardiogram to see if the valve severity changes with increasing cardiac output. If the patient is found to truly have severe aortic stenosis and demonstrates contractile reserve (with improvement in LVEF during exercise), then intervention either via aortic valve replacement or transcatheter aortic valve implantation is indicated. Even if no contractile reserve is demonstrated, intervention can still be considered, albeit at risk of higher mortality. In a haemodynamically unstable patient with AHF and severe aortic stenosis, balloon aortic valvuloplasty may be considered as a bridge to surgery. Vasodilators (nitrates and ACE inhibitors) should be avoided in the medical management of severe aortic stenosis.

In 90% of cases of mitral stenosis patients have preserved LV systolic function; however, AHF can be precipitated by the atrial tachycardia frequently associated with mitral stenosis. The physiological haemodynamic changes related to pregnancy also put pregnant women particularly at risk of pulmonary oedema. Medical management involves diuretics and rate control medication such as β‎-blockers. Patients may be considered for percutaneous or surgical valve intervention depending on their characteristics.

Severe mitral regurgitation causing AHF can be caused by a ruptured papillary muscle following an ischaemic event (typically right coronary artery obstruction) or ruptured chordae (ischaemic or degenerative) leading to a flail mitral valve leaflet. It can also be caused by leaflet perforation secondary to endocarditis. By causing an abrupt increase in preload, acute mitral regurgitation increases left atrial pressure and pulmonary venous pressure, leading to pulmonary oedema. The afterload is reduced and LVEF is usually supranormal to compensate for the additional regurgitating volume. Acute mitral regurgitation is a surgical emergency.

Acute aortic regurgitation is most commonly related to endocarditis; however, it can also result from aortic dissection affecting the aortic annulus (associated with bicuspid valve connective tissue aortopathy, e.g. Marfan’s disease or atherosclerosis). The acute rise in LV end-diastolic pressure impedes forward stroke volume and can lead to rapid deterioration. Again, this is a surgical emergency.

Although rare, peripartum cardiomyopathy (PPCM) is another cause of AHF, affecting 1/1000 pregnancies. It is unclear what the exact underlying mechanism is, but it has been reported to be due to an interplay of both autoimmune and antiangiogenic factors. Overall, it is estimated that 50% of patients with PPCM see a recovery in LV function over 6 months. Patients with PPCM should be treated as per standard AHF management as detailed in this section. Bromocriptine has an emerging role as a new agent for the treatment of PPCM. By acting as a dopamine agonist, it prevents the degradation of prolactin to 16 kDa prolactin, which is known to have cardiotoxic effects. In small trials, it has been shown to be effective in improving LVEF when combined with standard HF therapy: 58% versus 36% in the control group.

After stabilization


ACE inhibitors or ARBs should be started as soon as possible in patients not taking these agents who have impaired LV function. ACE/ARBs have an impact on LV remodelling and have long-term mortality benefits. β‎-Blockers should also be started as soon as possible once the condition has stabilized, e.g. once patients no longer require IV diuretics. In combination with ACE/ARB they have potential to improve LVEF substantially as well as having antiangina properties, reducing the risk of sudden cardiac death, and showing long-term mortality benefits. Both agents should be initiated at a low dose and the patient should have a clear ongoing plan for uptitration to their evidence-based target doses. Patients with AHF already taking β‎-blockers prior to decompensation should continue to take them as long as heart rate is >50 bpm, there is no high-degree AV block, and they are normotensive.

Mineralocorticoid receptor antagonists should be considered in patients with a low EF <35% in patients who are New York Heart Association (NYHA) class II –IV with potassium <5 mmol/l and GFR >30 ml/min. Care should be taken to monitor potassium levels and renal function whilst on them. Spironolactone has been shown to reduce all-cause mortality, sudden cardiac death, and hospitalization in this group with severe LV dysfunction by 30% in the landmark RALES (Randomised Aldactone Evaluation study). Alternatively, eplerenone has also been shown to have similar benefits as spironolactone, particularly post-MI (EPHESUS, EMPHASIS II).

Ivabradine lowers heart rate by blocking the I(f) channels in the sinoatrial node without affecting systemic BP. They are an option in patients in sinus rhythm with heart rate >75 bpm who remain in NYHA class II–IV and in whom β‎-blockers are either contraindicated or cannot be sufficiently titrated. Trials have shown their maximal benefit when combined with a β‎-blocker at target dose. They do not work in AF.

Digoxin is an option to control AF rates, particularly if uptitration of β‎-blockers is limited. There is an occasional role for digoxin for patients who remain symptomatic with severe LV dysfunction who are in sinus rhythm.

There is limited evidence for the combination of hydralazine and isosorbide dinitrate, particularly in Afro-Caribbean patients.

Patients should be educated on their fluid and salt intake allowances prior to discharge.


In HF PEF, the standard therapies used to treat systolic HF have not shown any benefit in trials. This includes trials done on β‎-blockers, ACE inhibitors, ARBs, mineralocorticoid antagonists, digoxin, and sildenafil. Therefore, the long-term management of HF PEF focuses on symptomatic relief from peripheral oedema with loop diuretics, control of hypertension, and arrhythmia.

Cardiac resynchronization therapy

The long-term management of HF REF must involve consideration of implanting a cardiac resynchronization therapy (CRT) device in patients with life expectancy >1 year. A CRT-P is a pacemaker that consists of a right atrial lead, RV lead, and a lead placed through the coronary sinus that paces the LV lateral wall on its epicardial surface. It allows for biventricular pacing, thus restoring synchronous ventricular contraction, improving LV function, morbidity, and mortality when implanted into patients with specific characteristics, namely patients in sinus rhythm with severe LV impairment with evidence of ventricular dyssynchrony. This device can also be combined to have additional defibrillator function (CRT-D) by the addition of an RV lead with defibrillator capability.

Large trials have demonstrated the benefit of CRT in patients who are NYHA class II–ambulatory IV, with a persistently low EF <35%, LBBB, evidence of dyssynchrony as demonstrated on the ECG as prolonged QRS >120 ms in sinus rhythm. Randomized controlled trials: Comparison of Medical Therapy, Pacing and Defibrillation in Heart failure (COMPANION) and Cardiac Resynchronisation in Heart failure (CARE-HF) showed a relative risk reduction in death of 24% and 36%, respectively for CRT-P devices, as well as a notable improvement in symptoms and exercise capacity. There was a relative risk reduction in further hospitalizations owing to worsening HF in 52% in patients with CRT-P in CARE-HF.

The consensus for CRT implantation in patients with non-LBBB is less certain and so remains a class IIa indication. Likewise is the uncertainty of CRT in patients with AF owing to challenges faced in achieving adequate biventricular pacing in patients with fast ventricular rate.


HF is a complex clinical syndrome that carries a huge burden on morbidity and mortality. It is characterized by failure of the heart to meet metabolic demands of tissues despite adequate filling pressures and is broadly divided into HF REF and HF PEF. AHF is a leading cause of hospitalization in patients over 65 years. It requires the simultaneous investigation and rapid initiation of management to avoid critical delay in restoring tissue oxygenation, organ perfusion, and providing symptomatic relief, while taking care to identify and treat key precipitating factors, e.g. ACS and arrhythmia to prevent further decompensation. Once stabilized and commenced on the standard neuroendocrine blockade therapy, consideration should be given to potential benefit gains from CRT-P/CRT-D. Further consideration of advanced HF therapy using ventricular assist devices while bridging to transplant may be necessary, in appropriate patients, following referral to a transplant centre (Figure 19.2).

Figure 19.2 Flow diagram illustrating management of AHF.

Figure 19.2 Flow diagram illustrating management of AHF.

Source data from European Society of Cardiology 2012, American Society of Cardiology 2013, NICE 2014.

Bacterial endocarditis

The spectrum of infective endocarditis

The term endocarditis refers to inflammation of the heart’s endocardial surface through whatever cause. Most commonly this is due to bacterial colonization, but endocarditis can occur with infection due to other pathogens (e.g. fungus) and non-infective causes (e.g. connective tissue diseases). Whilst important, these remain rare entities, and consequently the focus here is on bacterial infection.

Bacterial colonization of the endocardium is a serious and often devastating clinical problem. It is rare in the general population (incidence of 3–10 cases per 100 000 patient-years), but is relatively more common in the elderly and individuals with specific predisposing factors. Colonization occurs where the continuum of endocardial defences have been broken, for example, by implant of a valve prosthesis or injury from persistently turbulent bloodflow. Cardiac valves are particularly at risk as they lack a direct blood supply, restricting access by immune cells (and, during treatment, by systemic antibiotics). Once established, bacterial endocarditis (BE) is extremely difficult to clear and causes adverse effects by: 1) localized tissue destruction; 2) embolic infection; and 3) immunological damage due to circulating immune complexes. Antibiotic therapy forms the mainstay of treatment, but cardiac surgery is sometimes required. This section aims to introduce key concepts for the critical care physician, highlighting the 2015 ESC Clinical Guidelines as the recent consensus for best practice care.

Clinical syndromes

BE is classified by the status of the infected valve (prosthetic versus native) and by the temporal pattern of presentation. These dichotomies reflect the nature of the host–pathogen interaction due to factors such as bacterial virulence and integrity of local host defences.

Acute BE has rapid onset, with deterioration from normal status to severely unwell over days, features of systemic sepsis, and acute cardiac and end-organ dysfunction. The rapid onset leaves no time for cardiac compensation, yielding marked haemodynamic abnormalities. Acute BE is often associated with colonization by Staphylococcus aureus and is more commonly seen in IV drug users.

In contrast, subacute BE exhibits a more subtle presentation, often over weeks or months, typified by waxing and waning non-specific symptoms such as lethargy and weight loss, associated with intermittent fever. A high index of suspicion is required, and presentation is often masked by intermittent antibiotics targeted to suspected infection elsewhere. The α‎-haemolytic streptococcal organisms are frequently implicated. Subacute BE due to Streptococcus bovis can be associated with colonic malignancy.

Prosthetic valve endocarditis (PVE) accounts for 10–30% of all cases of BE, often presents atypically, and carries a worse prognosis.

Work-up and diagnosis

Whatever the pattern of presentation, diagnosis of BE always requires a high index of suspicion. The presence of foreign intracardiac material such as a valve prosthesis raises suspicion. The clinical features and investigation findings in BE are due to bacteraemia, endocardial tissue destruction, embolism, and immunological phenomena (Table 19.5).

  • Blood cultures identify bacteraemia (almost ubiquitous in BE) and facilitate strain- and sensitivity-targeted antibiotic treatment. At least three pairs of well-filled blood culture bottles should be taken at 30-minute intervals and from different sites before starting antibiotic therapy.

  • Echocardiography identifies endocardial lesions. Transthoracic echo (TTE) is first-line and should be performed in all patients where there is clinical suspicion. The sensitivity of TTE can be insufficient and, if TTE is negative, transoesophageal echocardiography may be required. If the pretest clinical suspicion for BE is low, then an absence of endocardial lesions on a good-quality TTE, with negative blood cultures, is usually sufficient to exclude the diagnosis.

  • Cardiac CT is useful in assessment of perivalvular lesions such as abscesses, and other imaging such as positron emission tomography/CT (PET/CT) can identify septic emboli as well as help discriminate endocardial lesions.

Table 19.5 Clinical features of infective endocarditis



Symptoms and signs



Systemic sepsis

Lethargy, fevers, rigors

Obtunded, febrile

Signs of septic shock

Blood cultures


High CRP and ESR

Endocardial tissue destruction

Native valve damage

Prosthetic valve dehiscence


Damage to conduction system



Reduced effort tolerance

Chest pain

Signs of valve incompetence (e.g. pulse character, heaving apex, murmur)

Signs of cardiogenic shock


Echo (TTE ± TOE): vegetations, abscess, valve incompetence

ECG: PR interval, heart block

CXR: pulmonary oedema

Embolic phenomena

Embolization of thrombus or vegetation

Splinter haemorrhages

Signs and symptoms of transient ischaemia or infarction in end organ, e.g. TIA or stroke, splenic infarct, bowel ischaemia

Cross-sectional imaging, e.g. MRI brain or CT abdomen

Markers of end-organ damage

PET/CT or radionucleotide scan for septic emboli

Immunological phenomena

Circulating immune complexes and immune complex deposition

Roth spots

Osler’s nodes

Microscopic haematuria

Evidence of glomerulonephritis

Raised ESR and CRP

Positive rheumatoid factor

CRP, C-reactive protein; CT, computed tomography; CXR, chest radiograph; ESR, erythrocyte sedimentation rate; MRI, magnetic resonance imaging; PET, positron emission tomography; TOE, transoesophageal echocardiogram; TTE, transthoracic echocardiogram.

Definitive diagnosis is pathological evidence of microorganisms in excised heart tissue or embolic infection, but the modified Duke criteria provide a framework for clinical diagnosis. In essence, these require the presence of bacteraemia with echocardiographic evidence of colonization or tissue destruction at the endocardial surface, or, if either of these is not confirmed, multiple less specific features (Table 19.6).

Table 19.6 Modified Duke criteria for diagnosis of infective endocarditis

Major criteria

Minor criteria

  1. 1. Blood culture positive for IE

    Typical microorganisms consistent with IE from two separate blood cultures


    Microorganisms consistent with IE from persistently positive blood cultures

  2. 2. Evidence of endocardial involvement on echocardiography

  1. 1. Predisposition, predisposing heart condition, or injection drug use

  2. 2. Fever, temperature >38°C

  3. 3. Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial haemorrhage, conjunctival haemorrhages, and Janeway lesions

  4. 4. Immunological phenomena: glomerulonephritis, Osler’s nodes, Roth’s spots, and rheumatoid factor

  5. 5. Microbiological evidence: positive blood culture but does not meet a major criterion or serological evidence of active infection with organism consistent with IE

Definite IE = 2 major, or 1 major + 3 minor, or 5 minor.

IE, Infective endocarditis.

Reprinted from Lukes A.S., Bright D.K., Duke Endocarditis Service. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings, pp. 200–209. Copyright (1994) with permission from Elsevier.


The priorities in BE are control of bacteraemia, clearance of endocardial colonization, and prevention of complications. The multidisciplinary endocarditis team will include specialists in cardiology, microbiology, and cardiac surgeons.

Antibiotic therapy

Primary management is with antibiotics. The typical combination is a bactericidal cell wall inhibitor (normally a β‎-lactam, or glycopeptide in penicillin allergy) synergized with an aminoglycoside. The initial empirical regime is determined by the nature of the clinical presentation (acute versus subacute, native versus prosthetic valve) and local patterns of antibiotic sensitivity.

  • In acute BE, staphylococcal cover is key, and the regime should include either flucloxacillin in native valve BE (8–12 g IV daily in four to six divided doses); vancomycin (1 g 12-hourly IV, modified according to renal function) should be used in PVE, suspected MRSA, or hospital-acquired infection.

  • Subacute presentation is often due to α‎-haemolytic streptococcal organisms and best treatment is with high-dose penicillin (7.2 g IV daily in six divided doses) or ampicillin/amoxicillin (2 g IV 6-hourly) plus aminoglycoside (e.g. gentamicin 1 mg/kg twice-daily).

  • Rifampicin is particularly used in PVE, added to the regime once the bacteraemia is cleared, but it can cause liver dysfunction.

There are many variations to this standard approach, so an individual patient’s treatment should be planned in close liaison with local microbiologists and tailored to the individual patient. In practice a lot of centres opt for a regime that covers Staphylococcus and Streptococcus in the empiric therapy (e.g. vancomycin, amoxicillin, and gentamicin together). Either way, once an organism is identified on blood culture, the regime can be targeted specifically to its susceptibilities. Local protocols vary, but a typical antibiotic course is 6 weeks. Some low-risk patients may be suitable for outpatient antibiotic therapy or shortened duration of therapy.


Often medical treatment is sufficient, but surgery during the acute phase may be required. Ultimately, surgery is required in around half of BE patients. Risk stratification allows complications to be anticipated, identified early, and managed expectantly. High-risk patients, especially with left-sided endocarditis, should be discussed early with a cardiac surgical centre. At all times prior to surgery, physicians should consider optimization to assist surgical planning and reduce intraoperative risk. Measures might include nutritional supplementation (e.g. chronic presentation with cachexia or acute presentation in a poorly nourished drug user), management of anaemia (e.g. IV iron replacement), physiotherapy to support physical conditioning, or coronary angiography.

Specific complications that warrant surgical management include the following:

Worsening HF

HF complicates up to 50% of BE and is normally due to acute valve dysfunction. More gradual onset allows some cardiac compensation, but acute volume overload appearing over days (e.g. acute aortic valve BE with acute severe aortic regurgitation) can result in rapidly worsening HF. The patient’s acute HF is stabilized with standard therapy (e.g. respiratory support, inotropes, balloon pump) while antibiotics achieve control of bacteraemia and some control of endocardial infection, but early valve replacement is required.

Uncontrolled infection

In some cases the endocardial infection is poorly controlled and requires surgical clearance. This can reflect failure of clearance due to resistant organisms or perivalvular extension with formation of intracardiac abscesses. Aortic root abscesses can interrupt cardiac conduction causing heart block, and PR interval prolongation is an early sign. Cardiac pacing may be required. Surgery aims to remove infected intracardiac material, drain abscesses, and repair damaged structures, but it is often extremely challenging.

Evidence of systemic embolism

Vegetations or thrombi can be the original nidus for infection and/or can grow as inflammatory collections during disease evolution. These can break off and embolize to distant organs, most devastatingly the brain, causing transient cerebral ischaemia or stroke. Small, asymptomatic splenic infarcts are frequently seen. The persistent presence of large vegetations (e.g. >10 mm) may support an early surgical strategy. Once embolism has occurred there is risk for recurrence and treatment is with surgery to remove the embolic source.

Recovery and prognosis

Survival at 1 year is around 80–90%, with 60–70% survival at 5 years. However, PVE carries higher risk of complications requiring surgery and significantly worse prognosis, with 20–40% mortality in hospital. Late complications include recurrence of infection and HF. Recurrence of BE is rare but more likely with resistant organisms, significant comorbidities, and inadequate initial antibiotic therapy. Surgery may be required if valves have been significantly damaged.


The best prevention for BE is maintenance of good dental hygiene, although prophylactic antibiotics have long been used in certain patient groups undergoing invasive procedures, with a view to suppressing transient bacteraemia and reducing the likelihood of endocardial colonization. However, the area remains controversial since the NICE Guidelines in 2008 that specifically recommended against taking this measure based on cost-ineffectiveness and lack of evidence for efficacy. This view has received criticism, and at present the ESC guidelines recommend use of prophylaxis in patients at the highest risk, including those who are undergoing dental procedures (e.g. amoxicillin 2 g as a single dose orally, 30–60 min prior, or clindamycin 600 mg in penicillin allergy). Antibiotic prophylaxis is not recommended in intermediate- and low-risk patients, and any patient undergoing non-dental procedures. In practice, the decision to use prophylaxis will rely on assessment of the individual patient’s risk and discussion between patient and physician (Box 19.3).

Adapted from European Heart Journal, 36, 44, Habib G., Lancellotti P., Antunes M. J. et al., 2015 ESC Guidelines for the management of infective endocarditis: The Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM), pp. 3075–3128. Copyright © 2015, Oxford University Press.


BE remains a challenging condition to diagnose and treat, and its manifestations and complications can carry significant morbidity and mortality. Blood cultures and echocardiography remain the key diagnostic tools, although there is an increasing role for cardiac CT and PET/CT for identifying intracardiac and end-organ complications. Multidisciplinary team management is key, with careful attention to risk stratification and early referral to a cardiac surgical centre if needed.

Multiple choice questions and further reading

Cardiovascular disorders Interactive multiple choice questions to test your knowledge on this chapter and additional further reading can be found in Appendix Chapter 19 Multiple choice questions and further reading