Origins of cardiac dysfunction: Irregular contractions with suboptimal filling

Pre-syncope is a feeling of faintness or lightheadedness without loss of consciousness, may be described as dizziness or muscular weakness and include blurred vision, mild disorientation, change in body temperature and nausea

With loss of consciousness, i.e., seizure disorders, concussion

Without loss of consciousness, i.e., psychogenic “pseudo-syncope”

Major morbidity reported in 6%1eg, fractures, motor vehicle accidents

This may suggest more malignant causes such as ventricular tachycardia.

Critical as most important factor in prognosis and risk stratification – cardiovascular causes of syncope have the highest mortality risk.

Syncope vs. dizziness, presyncope, drop attacks, vertigo, & seizures.

Review patient’s medication list: note any recent changes in medications/doses

Physical exam: Full examination of all systems, with particular focus on cardiovascular and neurological systems

Past medical history- especially history of similar episodes, cardiac and neurological conditions

Eyewitness account of event if available: What happened, appearamce of patient, breathing pattern, duration, abnormal movements, incontinence etc.

Circumstances prior to episode e.g. position, activity, precipitating events, recent illnesses etc.

Symptoms at onset of event e.g. headache, nausea, chest pain, palpitations, aura

Proarrhythmic/antihypertensives/antianginal/QT prolonging agents

Tachycardia, bradycardia, irregular pulse, low volume pulse, pulsus parvus et tardus

Focal neurological abnormalities e.g. weakness, signs of Parkinsonism

Laboratory investigations: FBC, renal profile, glucose, D-dimer (if suspected PE), blood alcohol level or drug screen if indicated.

Outcome: Positive test is defined by cardiac asystole for 3 seconds or longer, or 50 mmHg fall in systolic BP, or 30 mmHg drop in SBP with reproduction of symptoms. (ESC guidelines). Reproduction of symptoms is necessary for Carotid Sinus Syndrome diagnosis

previous TIA/stroke in last 3 months (unless recent carotid duplex study).

Acute MI/Ischemia: Neural reflex bradycardia – vasodilatation, arrhythmias

Hypertrophic cardiomyopathy: Limited output during exertion (increased obstruction, greater demand), arrhythmias, neural reflex

Acute aortic dissection: Neural reflex mechanism, pericardial tamponade

Pulmonary embolus/pulmonary hypertension: Neural reflex, inadequate flow with exertion

Aortic stenosis – Limited output, neural reflex dilation in periphery

Myocyte hypertrophy - contractility – desensitisation - loss – replacement

Ventricular filling- e.g. with poor venous return, poor volume, Starling’s law

Ventricular ejection e.g. of blood from the left ventricle (pump function)

Heart failure occurs when the heart is unable to pump blood at a rate [cardiac output] sufficient to meet the metabolic demands of the tissue

Reduced ejection fraction (EF) (systolic HF) Vs Preserved EF (diastolic HF) filling

∴ small amount of blood is emptied from chamber i.e EF preserved BUT CO is low

Heart rate = beats per minute, Autonomic influences on sinoatrial node

2) increased ventricular filling (end diastolic volume) and increased preload (initial stretching of cardiac myocyte prior to contraction)

Retain salt and water (RAAT- Renin Angiotensin Aldosterone System)- Expand blood volume , increases stroke volume

Inotropes deployed in severe pump failure

(ANP levels are a good serum marker of heart failure in clinical practice)

Left-sided or right-sided heart failure can occur independently and failure of one side can produce strain in the other causing global heart failure

Ischaemic heart disease - Muscle failure and therefore pump failure

Hypertension - Increased pressure to pump against [remember BP = CO x PR]

Other Cardiac muscle diseases eg cardiomyopathy or myocarditis

Arrhythmia- Rate too fast to empty ventricle at each beat or to slow [remember CO = SV x HR)

“Congestion” of the pulmonary venous circulation → pulmonary oedema & dyspnoea

Hypo-perfusion of systemic tissue →organ dysfunction e.g. mesenteric ischaemia or renal failure

Dyspnoea which may limit exercise tolerance - (pulmonary oedema - orthopnoea / nocturnal cough /paroxysmal nocturnal dyspnoea)

Fatigue - Low output from left ventricle with peripheral hypoperfusion

Right ventricular failure due to pulmonary venous hypertension – peripheral stasis

Why does the patient have dyspnoea?Fluid retention in left heart causes pulmonary venous hypertension, which may lead to pulmonary oedema and reduced ability to aerate the lung alveoli with consequent reduced oxygenation of blood

Findings reflect the underlying disease process / index event (e.g. Infarction; valve abnormality)

Left atrium may be dilated eg mitral stenosis– risk of atrial fibrillation and thrombus.

Inflammation of myocardium e.g. if the heart is failing due to viral myocarditis

Kidney- Decreased renal perfusion activates renin angiotensin system with expansion of blood Volume --> Can contribute to pulmonary oedema

Brain- Hypoxic encephalopathy in advanced heart failure

Chronic eg chronic angina- Pulmonary congestion and often mild dyspnoea and oedema

Parenchymal diseases of the lung e.g. cor pulmonale [pulmonary heart disease]

Diseases of pulmonary vasculature - primary pulmonary hypertension, recurrent pulmonary thromboembolism

*Left Heart failure will cause secondary right heart failure when the latter is severe

increased Pulmonary artery pressure [pulmonary vascular bed] - increased RV afterload – RV remodelling

Right ventricular dilatation + /- hypertrophy; AV Ring stretching – Tricuspid Incompetence

Reduced plasma [ protein ] oncotic pressure (fluid leaves vessels)

Lifestyle- Salt and fluid restriction decreases intra vascular volume

2. Pathologic remodelling causing left ventricular hypertrophy +/- dilatation.

3. Compensatory adaptations initially maintain cardiac output, however ultimately result in cellular changes, fibrosis and pump failure.

4. Reduced cardiac output causes organ hypoperfusion and pulmonary venous congestion and pulmonary oedema

increased demand, reduced supply = Narrowed Atherosclerotic Coronary Artery

Occluded Thrombosed atherosclerotic Coronary Artery

Left coronary artery - 1.5cms and gives the interventricular LAD and the (L) circumflex. The LAD supplies the apex, anterior 2/3 of septum and the anterior wall of the LV.

Right coronary artery classically the posterior wall “inferior” in ECG.The right coronary artery usually supplies the posterior of the septum

Usually chest pain caused by exercise and relieved by rest and – often not clear-cut.

Assessment via angiography. Often if autopsy done → microscopic myocardial fibrosis. Why?

Angina may be worsened by anaemia or increased cardiac mass i.e. hypertrophy- may reflect important non-cardiac disease

Precipitated with progressively less effort- Often occurs at rest, and tends to be of more prolonged duration.

Induced by disruption of an atherosclerotic plaque (plaque rupture) and secondary thrombus.

Sudden large coronary thrombosis on a ruptured atheromatous plaque

Secondary to an arrhythmia in chronic ischaemic heart disease as defined above.

Usually reflects unrelieved coronary artery occlusion evolving to tissue death - Dynamic process and can be reduced by coronary reperfusion following “stenting”

Certain plaques more likely to thrombose – lipid rich with fibrous cap cracks

Crushing central chest pain, unrelieved by rest; accompanied by weakness, sweating, nausea & vomiting - Radiates commonly to left shoulder and jaw

May be “silent” present as heart failure (esp in elderly) arrhythmia – confusion – weakness.

Coronary atheroma --> plaque rupture and subsequent thrombosis initiates ischaemia – possibly reversible for 6 – 12 hours.

Necrosis of myocardium begins 30 mins after occlusion and progresses from the subendocardial myocardium through the full thickness of the myocardium to the pericardial zone. (Transmural infarct)

Most untreated episodes of ischaemia cause --> Transmural infarction.

NB Subendocardial (AKA Non ST-elevation MI--NSTEMI) infarction more likely in incomplete artery occlusion or may develop in prolonged shock.

Schematic representation of the progression of myocardial necrosis after coronary artery occlusion. Necrosis begins in a small zone of the myocardium beneath the endocardial surface in the center of the ischemic zone. This entire region of myocardium (shaded) depends on the occluded vessel for perfusion and is the area at risk. Note that a very narrow zone of myocardium immediately beneath the endocardium is spared from necrosis because it can be oxygenated by diffusion from the ventricle. The end result of the obstruction to blood flow is necrosis of the muscle that was dependent on perfusion from the coronary artery obstructed. Nearly the entire area at risk loses viability.

Plaque rupture with secondary thrombosis- can cause a myocardial failure or a fatal arrhythmia

ECG (EKG): quick, easy and gives information about site and vessel involved as well as information about arrhythmias.

Enzyme levels give some idea of extent of infarct, latter depending on location of obstruction, significance of vessel, degree of myocardial hypertrophy and presence of a collateral coronary circulation.

Certain subtypes of troponin (I and T) are indicators of damage to the myocardium and can be measured in the blood by immunoassay techniques. Must be repeated to look for a rise

- myocarditis

Day 7 – 14: Ongoing repair process with resorption of dead tissue and granulation tissue at edges. Macroscopic – depressed area with red edges.

Week 2-8: Evolving fibrosis and decreasing vascularity. Macroscopic – grey white tissue

Week 8: Dense fibrosis. Macroscopic depressed thinned myocardium and scar.

Day 1 Coagulative necrosis on left characterised by non-nucleated wavy fibres with oedema causing widened space between fibres – rare neutrophils also present. Microscopic features of myocardial infarction and its repair. One-day-old infarct showing coagulative necrosis along with wavy fibers (elongated and narrow), compared with adjacent normal fibers (at right). Widened spaces between the dead fibers contain edema fluid and scattered neutrophils.

Day 2-7 Necrotic myocardium with polymorphs

Day 7 Soft yellow Myocardium [Cross section of left ventricle]:

Coronary artery disease (CAD) is almost always due to atheromatous narrowing and subsequent occlusion of the an artery.

In affluent societies, CAD causes severe disability and more death than any other disease, including cancer.

It manifests as angina, silent ischaemia, unstable angina, myocardial infarction, arrhythmias, heart failure, and sudden death.

Pathogenesis of Atherosclerotic Plaques:
Endothelial damage --> Protective response results in production of cellular adhesion molecules --> Monocytes and T lymphocytes attached to ‘sticky’ surface of endothelial cells --> Migrate through arterial wall to subendothelial space --> Macrophages take up oxidised LDL cholesterol --> Lipid-rich foam cells --> Fatty streak and plaque --> Plaque rupture, thrombus formation, blockage of Artery

Usually associated with the presence of significant obstructive coronary disease (stable disease)

Angiogram of “normal” individual

Evidence of narrowing - just 1 spotted

If the supply of oxygen remains below a critical value, a sequence of events leads to cell death

Clinically determined by an elevations of circulating troponin (a biochemical marker of myocardial injury), and of cardiac enzymes (e.g., the cardiac isoform of creatinine kinase) and changes in the surface ECG

The pain has a characteristic distribution in the chest, arm and neck, and is brought on by exertion, cold or excitement.

Coronary circulation has a very high basal oxygen consumption

Also has a very high oxygen extraction rate, therefore increased demand must be met by increased flow

Most of the oxygen demand must be met in diastole

usually caused by fixed narrowing(s) of the coronary arteries by atheroma, Narrowing of the aortic valve (‘aortic stenosis’) can also cause angina by reducing coronary blood flow even in the absence of coronary artery narrowing.

together with treatment of the underlying atheromatous disease, usually including a statin, and prophylaxis against thrombosis with an antiplatelet drug, such as aspirin

This is characterised by pain that occurs with less and less exertion, culminating in pain at rest.

The pathology is similar to that involved in myocardial infarction, namely platelet–fibrin thrombus associated with a ruptured atheromatous plaque, but without complete occlusion of the vessel.

Antiplatelet drugs (aspirin and/or an ADP antagonist such as clopidogrel or prasugrel) reduce the risk of myocardial infarction in this setting,

and antithrombotic drugs add to this benefit at the cost of increased risk of haemorrhage.

This is relatively uncommon. It can occur at rest and is caused by coronary artery spasm, often in association with atheromatous disease.

In a stressed heart, the renin-angiotensin system is activated due to reduced tissue perfusion.

Angiotensin I is converted by Angiotensin Converting Enzyme (ACE) to Angiotensin II expressed on the surface of the endothelium. ACE also inactivates bradykinin- an inducer of pain

Ang II causes vasoconstriction (increased afterload) and releases aldosterone, which causes Na+ and water retention (congestion/oedema).

protection of the vessel from injurious consequences of platelets activation

Enhanced expression of cell adhesion proteins on endothelial cells-enabling monocyte adhesion

Hypertension, hypercholesterolemia, smoking, diabetes mellitus and heart failure are associated with diminished local synthesis of nitric oxide

Nitric oxide (NO) is a soluble gas continuously synthesized from the amino acid L-arginine in endothelial cells by the constitutive enzyme nitric oxide synthase (NOS).

Nitroglycerin, used for over 150 years, is a potent vasodilator in the treatment of angina pectoris and chronic heart failure, and, in its extended release forms, it still remains first-line drug therapy for many patients.

Nitrates, usually in the form of a sublingual preparation, are the first-line therapy for the treatment of acute anginal symptoms. Patients should be instructed to use them at the onset of angina or for prophylaxis of anginal episodes

Most of the antiischemic efficacy of nitrates pertains to their ability to decrease myocardial oxygen demand as a result of systemic vasodilatation rather than any activity as a coronary vasodilator

Nitrates do not have a direct effect on cardiac chronotropy or inotropy.

Nitrates also have significant antiplatelet and antithrombotic properties

Repeated administration of nitrates to smooth muscle preparations in vitro can result in tolerance

This leads to a diminished vascular relaxation in response to each dose

Tolerance to the anti-anginal effect of nitrates does not occur to a clinically important extent with ordinary formulations of short-acting drugs (e.g. glyceryl trinitrate)

but tolerance does occur with longer-acting drugs (e.g. isosorbide mononitrate)

or when glyceryl trinitrate is administered by prolonged intravenous infusion or by frequent application of slow-release transdermal patches

It is usual to require a nitrate free period of 10-12 hours in each 24 hours

Excessive use can also result in the formation of methaemoglobin**, an oxidation product of haemoglobin that is ineffective as an oxygen carrier

Postural Hypotension is a failure of the a vasoconstricting reflex to occur when a person changes from lying to sitting, or sitting to standing. As a result blood pools in dilated blood vessels and the patient may faint.
*Formation of methhaemoglobin seldom occurs when nitrates are used clinically but is induced deliberately with amyl nitrite in the treatment of cyanide poisoning , because methaemoglobin binds and inactivates cyanide ions.

Another group of anti-anginal drugs slow the heart and hence reduce metabolic demand - β-adrenoceptor antagonists

Calcium antagonists (CAs) reduce angina by inhibiting inward calcium currents through the cell membrane in many tissues, including the myocardium, cardiac conduction tissues, and vascular smooth muscle cells in both coronary arteries and peripheral vessels. They are also called Calcium Channel Blockers Intracellular calcium deprivation relaxes smooth muscle cells, causing vasodilation in the peripheral and coronary beds and increased coronary blood flow.

Therapeutically important calcium antagonists act on L-type channels.

Properties: Peripheral and coronary vasodilators, negative inotropic action

Properties: Additional negative chronotropic and inotropic actions

Properties: Additional negative chronotropic and inotropic actions

They can favourably alter the ratio of supply and demand in chronic stable angina

Verapamil and diltiazem, slow sinoatrial (SA) and atrioventricular (AV) nodal conductions to reduce heart rate and depress contractility under physiological conditions.

In the periphery they cause relaxation of vascular smooth muscle. They reduce arteriolar pressure (afterload)

These drugs lower the frequency of angina, lower the need for nitrates, increase treadmill walking time, and improve ischaemic ST-segment changes on exercise testing and electrocardiographic monitoring.

Calcium antagonists have been shown to be equally effective as beta-blockers in the management of stable angina.

ESC guidelines on stable coronary artery disease for the management of stable angina consider either a beta-blocker or a CA as appropriate first-line treatment.

Dihydropyridines (DHPs) lower BP and myocardial wall tension to reduce myocardial oxygen consumption.

A rise in coronary blood flow further contributes to correcting myocardial oxygen imbalance.

Common side effects: Hypotension, oedema, dizziness, flushing, nausea, constipation

Most common: longer-acting forms of diltiazem and verapamil, amlodipine, or felodipine.

Good oral absorption Many have low bioavailability due to hepatic first-pass metabolism, primarily by CYP3A4.

Calcium blockers should be tried in patients who cannot tolerate beta-blockers.

Other negative chronotropic or inotropic agents to produce bradycardia, heart block, or HF has been reported.

Some statins (atorvastatin and simvastatin), macrolide antibiotics, cimetidine and grapefruit juice may raise the effective level of Cas

Angiotensin-converting enzyme inhibitors (ACEi’s) lower total peripheral resistance by blocking the actions of ACE, the enzyme that converts angiotensin I to angiotensin II

Patients with stable angina pectoris who have diabetes, hypertension, proteinuria, or chronic renal disease or those with impaired left ventricular systolic function (left ventricular ejection fraction <40%) and all post-MI patients should also be treated with an ACE inhibitor

Block the activation of angiotensin II at AT1 receptors in smooth muscle cells of blood vessels, cortical cells of the adrenal gland, and adrenergic nerve synapses.

*Most sartans, or their metabolites (e.g., losartan) are inverse agonists.

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have known benefits for a subset of patients with hypertension, diabetes mellitus, decreased left ventricular ejection fraction (less than 40 percent), or chronic kidney disease

All patients with stable vascular disease are likely to derive some benefit from these drugs, to a degree approximately proportional to the level of baseline risk.

ACE 2 enzyme – trans membrane enzyme found in lung epithelium, endothelium, heart, GI tract- converts Ang II into Ang 1-7

Ang 1-7 is vasodilator, raises NO, it is a counter balance to Ang II

Pharmaco –kinetics: Prodrug – active metabolite enalaprilat t 1/2 ∼11 h Dose 1–2 times daily

Lisinopril, perindopril, ramipril, trandolapril are similar. Some are licensed for distinct uses (e.g. stroke, left ventricular hypertrophy)

Reversible renal impairment (in patients with renal artery stenosis)

Adverse effects: Hypotension, Reversible renal impairment (in patients with renal artery stenosis)

Pharmaco –kinetics: t 1/2 5–10 h Long-acting because receptor complex is stable

Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins, and the heart chambers. This is traditionally done by injecting a radio-opaque contrast agent into the blood vessel and imaging using X-ray based techniques such as fluoroscopy.

Diltiazem, teratogenic in animals, use if needed

Most sartans, or their metabolites (e.g., losartan) are inverse agonists.

Treating vascular stenosis with Drug-eluting stentsa surgical, rather than a Pharmacological solution?

Common primary feature - systemic thromboembolism in the late stages in critically ill patients

1) Conversion from ‘quiescent’ state to active ‘haemostatic’ state

2) Initial platelet tethering is mediated as von Willebrand factor, deposited in the subendothelial matrix of the damaged vessel wall, interacts with GPIbα of the GPIb-IX-V complex

3) Particularly important at high shear rates supporting platelet translocation (decelerating platelets and keeping them in close contact with the endothelium) over the subendothelium, but not stable adhesion

Coronary Artery Disease- Myocardial infarction (MI) treatment and secondary prevention- Unstable angina

Adhesion, activation and aggregation of platelets at the site of vascular injury have a pivotal role in the formation of arterial thrombi and, therefore, antiplatelet therapy is the cornerstone of treatment of patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) – angioplasty with stent

Vessel injury at artherosclerotic plaque initiates the coagulation cascade, triggering thrombin generation.

Antiplatelet therapy is the mainstay for the treatment of acute and chronic arterial disease

Currently, four main classes of antiplatelet therapies are clinically available for oral and intravenous administration in patients with ACS (unstable angina, MI) or following PCI (e.g., stent): 1) the cyclooxygenase (COX)-1 inhibitor aspirin (ASA, aspirin); 2) the ADP P2Y12 receptor antagonists clopidogrel, prasugrel, ticagrelor and cangrelor; 3) the glycoprotein IIb/IIIa inhibitors (GPIs) abciximab, eptifibatide and tirofiban; 4) the thrombin protease-activated receptor (PAR)-1 inhibitor vorapaxar

Platelets have reduced capacity to activate, thus preventing platelet aggregate formation

*This is why aspirin works – only COXI that has this effect. Other NSAIDs if taken with aspirin will reduce these effects!

Platelet life-span is 10-12 days- 10% of platelet population is replaced daily

Platelets are anucleate i.e., have no nucleus- They are therefore unable to synthesise new proteins

Aspirin inhibits COX irreversibly. Therefore, aspirin treatment irreversibly inhibits platelet COX for the remaining life of the platelet. However, non-platelet COX can recover within 4-8 hours as all other cells can regenerate new COX protein in this time

We can achieve platelet-specific action of aspirin by pharmacokinetic manipulation

Most cells, except platelets, will recover within 4-8 hours by de novo synthesis of COX

Repeated administration is likely to cause gastric ulceration and other side effects

Daily dosage will cumulatively inhibit all platelet COX but non-platelet COX will only be minimally affected

Benefit of ASA is achieved at low doses (75-100 mg daily) (25% >40 y.o., USA)- Reduced mortality by 25%

Can be used in combined with other antiplatelet drugs (clopidogrel)

Ubiquitous expression of P2Y1 receptors in other tissues of the body – lack of specificity, many trials ongoing

P2Y12 receptors highly expressed on the platelet surface – clopidogrel (P2Y12 antagonist) - most widely used as an antithrombotic agent - recommended in many published guidelines

Covalent binding to cysteine sulphydryl residues, irreversibly blocks the P2Y12 ADP receptor

Blocking the P2Y12 receptor prevents the amplification of the signal that results in a larger aggregate and inhibits TxA production

Prasugrel is also a prodrug, requires single oxidation step for biological activity activated by CYP 3A5 (CYP 2B6, minor)

More rapid onset of action after oral administration preferred in ACS

Achieves greater and more consistent platelet inhibition in individual patients (less inter-individual variability)

Higher risk of bleeding; contraindicated after stroke and TIA, >75 y.o.

Clopidogrel is a prodrug which is metabolised by hepatic cytochrome P450 enzyme CYP2C19 in a 2-step oxidation process*

Ticagrelor is metabolically active (not a pro-drug) does not require cytochrome P450 enzyme activation

Rapidly absorbed and directly and reversibly inhibits the platelet P2Y12 receptor through allosteric modulation

Short half-life of approximately 7 hours, ticagrelor requires a twice daily dosing

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor blocker (irreversible / reversible) is indicated for acute high-risk patient with ACS and in those undergoing coronary stenting

GPIIb /IIIa receptor binds to RGD motifs on fibrinogen to cross-link platelets & promote aggregation

Mechanism of action: Ligands mimic the RGD site and bind GPIIb/IIIa, preventing interaction with fibrinogen

Abciximab is composed of 7E3 Fab fragments - Chimeric human / murine monoclonal antibody

Tirofiban (small molecule inhibitor)- Synthetic mimetic of the RGD sequence of fibrinogen

Used for acute cardiac ischemic events in patients with angina, myocardial infarction

Side effects: Severe bleeding, hypotension, Cardiovascular failure, arrhythmias, fibrillation. = peptide effects at several sites

Abciximab t ½ (plasma) 2 hours. However, 29 & 13% of bound remains on the receptor after 8 & 15 days.

Endocarditis in persons who inject drugs: often right-sided (Tricuspid valve)

Healthcare-related endocarditis resulting from invasive procedures

Resource rich countries: the mean age of patients with endocarditis has increased:

rheumatic fever has declined in incidence

increasing use of implantable cardiac devices and heart valves

Investigations of, or procedures (e.g. surgery) involving, the gastrointestinal, genitourinary or upper respiratory tracts

Usually there is a defect/lesion causing turbulence in blood flow resulting in damage to the endocardial surface with platelets/fibrin aggregated on the surface

Bloodstream infection following dental or other procedure (large numbers of bacteria in the blood)

Bacteria adhere to clot/aggregate & a vegetation develops: layers of platelets/fibrin, bacteria, platelets/fibrin/bacteria etc.

Chlamydia, Q fever, brucella, legionella, mycoplasma, bartonella (diagnosis using serology or PCR)

HACEK organisms - fastidious (require prolonged incubation (grow slowly on culture plates) ~2%

HISTORY: Non-specific symptoms Malaise, fatigue, weight loss, arthralgia/ myalgia

Hands: splinter haemorrhages

Arterial emboli (white leg), ‘stroke’, pulmonary infarcts (drug users)

There may be signs of sepsis, respiratory symptoms (emboli), lung abscess(es)

The outcome is generally good however there may be poor compliance amongst persons who inject drugs

Blood cultures- Ideally three sets taken before starting antibiotics at least one hour apart

Echocardiography- (+other imaging) transoesophageal (TOE) if available, is superior to transthoracic (TTE)

Other investigations include serology (e.g. Q fever), PCR, ESR/CRP (non specific), urinalysis, FBC

Blood cultures- Ideally three sets taken before starting antibiotics at least one hour apart

Echocardiography- (+other imaging) transoesophageal (TOE) if available, is superior to transthoracic (TTE)

Other investigations include serology (e.g. Q fever), PCR, ESR/CRP (non specific), urinalysis, FBC

Recent advances in imaging techniques have resulted in an improvement in identification of endocardial involvements and extracardiac complications of infective endocarditis.
The addition of the results of these imaging modalities may improve the sensitivity of the modified Duke criteria

Atrial fibrillation/flutter with rapid ventricular rate (eg, pre-excitation syndrome, WPW)