Cardiac conduction system (Anatomy and physiology)
Arrhythmias (Pathology and Pharmacology)
1. Sudden Cardiac Death
2. Atrial Fibrillation
3. Infective Endocarditis
4. Rheumatic Fever
Sudden Cardiac Death
A 68-year-old man with a history of hypertension, hyperlipidemia, smoking for 35 years, and previous percutaneous coronary angioplasty is witnessed suddenly falling to the ground while shoveling his sidewalk. He had not complained of symptoms while shoveling. The emergency medical personnel who responded to the 911 call find him unconscious, pale, and without a pulse. After the pads from an automated defibrillator are attached, the patient is noted to be in ventricular fibrillation.
- Describe the features characterizing sudden cardiac arrest associated with loss of pumping action of the heart
Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) refer to the sudden cessation of cardiac activity with hemodynamic collapse, typically due to sustained ventricular tachycardia/ventricularfibrillation. These events mostly occur in patients with structural heart disease (that may not have been previously diagnosed), particularly coronary heart disease.
Sudden cardiac arrest usually results from an electrical disturbance in your heart that disrupts its pumping action, stopping blood flow to the rest of your body.
The sinus node generates electrical impulses that flow in an orderly manner through your heart to synchronize the heart rate and coordinate the pumping of blood from your heart to the rest of your body.
… arrhythmia called ventricular fibrillation — when rapid, erratic electrical impulses cause your ventricles to quiver uselessly instead of pumping blood.
- Review the epidemiology of sudden cardiac arrest in adolescents and young adults and beyond the age of 35 years
Sudden cardiac death is a rare but catastrophic event in children and young adults (<35 years) with the incidence ranging between 0.8 and 2.8/100,000 person-years.
The incidence of SCD in children and young adults (<35 years) varies, according to the literature, between 0.8 and 2.8/100,000 person-years . Ischaemic heart disease and dilated cardiomyopathy is the most common cause of SCD in the elderly population.
On the contrary, inherited or congenital cardiovascular disorders are the main cause of SCD in children and young adults . The athletes participating in competitive sports, requiring systematic training and regular competition against others, are particularly at higher risk of SCD [8,9].
In 1988 Thiene et al. have published the study of 60 persons (<35 years) who had died suddenly in the Veneto Region (Italy) . They found morphologic features of right ventricular cardiomyopathy (ARVC) in 12 of them. The authors suggested that ARVC might have been more frequent than previously thought and represented an important cause of sudden death in the young.
- Discuss the pathobiology of sudden cardiac arrest
As much as 70 percent of SCAs have been attributed to CHD – coronary heart disease. Among patients with CHD, SCA can occur both during an acute coronary syndrome (ACS) and in the setting of chronic, otherwise stable CHD (often such patients have had prior myocardial damage and scar that serves as a substrate for SCA).
SCD – sudden cardiac death is indeed more common in the absence of an identifiable acute cardiac event.
Coronary heart disease — As much as 70 percent of SCAs have been attributed to CHD. Among patients with CHD, SCA can occur both during an acute coronary syndrome (ACS) and in the setting of chronic, otherwise stable CHD (often such patients have had prior myocardial damage and scar that serves as a substrate for SCA). SCD is indeed more common in the absence of an identifiable acute cardiac event. (See “Epidemiology of coronary heart disease” and “Clinical features and treatment of ventricular arrhythmias during acute myocardial infarction” and “Incidence of and risk stratification for sudden cardiac death after acute myocardial infarction”.)
The arrhythmic mechanisms and the implications for SCA survivors are different in these two settings. (See “Prognosis and outcomes following sudden cardiac arrest in adults”.)
Other structural heart disease — Other forms of structural heart disease, both acquired and hereditary, account for approximately 10 percent of cases of out-of-hospital SCA. Examples of such disorders include the following:
●Heart failure and cardiomyopathy in which SCD is responsible for approximately one-third of deaths. (See “Ventricular arrhythmias in heart failure and cardiomyopathy”.)
●Left ventricular hypertrophy due to hypertension or other causes. (See “Left ventricular hypertrophy and arrhythmia”.)
●Hypertrophic cardiomyopathy. (See “Hypertrophic cardiomyopathy: Assessment and management of ventricular arrhythmias and sudden cardiac death risk”.)
●Arrhythmogenic right ventricular cardiomyopathy. (See “Arrhythmogenic right ventricular cardiomyopathy: Pathogenesis and genetics”.)
●Congenital coronary artery anomalies. (See “Congenital and pediatric coronary artery abnormalities”.)
●Mitral valve prolapse. (See “Natural history of chronic mitral regurgitation caused by mitral valve prolapse and flail mitral leaflet”.)
Absence of structural heart disease — In different reports, approximately 10 to 12 percent of cases of SCA among subjects under age 45 occur in the absence of structural heart disease [13,14], while a lower value of about 5 percent has been described when older patients are included [15,16]. (See “Sudden cardiac arrest in the absence of apparent structural heart disease”.)
This can occur in a variety of settings:
●Brugada syndrome. (See “Brugada syndrome: Clinical presentation, diagnosis, and evaluation”.)
●Idiopathic VF, also called primary electrical disease. (See “Sudden cardiac arrest in the absence of apparent structural heart disease”, section on ‘Idiopathic VF’.)
●Congenital or acquired long QT syndrome (table 2). (See “Congenital long QT syndrome: Epidemiology and clinical manifestations” and “Acquired long QT syndrome: Definitions, causes, and pathophysiology”.)
●Arrhythmogenic right ventricular cardiomyopathy. (See “Arrhythmogenic right ventricular cardiomyopathy: Anatomy, histology, and clinical manifestations”.)
●Familial polymorphic ventricular tachycardia, also called “catecholaminergic polymorphic VT.” (See “Catecholaminergic polymorphic ventricular tachycardia and other polymorphic ventricular tachycardias with a normal QT interval”.).
●Familial SCD of uncertain cause.
●Wolff-Parkinson-White syndrome. (See “Epidemiology, clinical manifestations, and diagnosis of the Wolff-Parkinson-White syndrome”, section on ‘Ventricular fibrillation and sudden death’.)
- Discuss the role of ventricular fibrillation, pulse-less ventricular tachycardia, asystole, and pulse-less electrical activity
Intro – In about 5%–10% of cases of SCD, no underlying heart disease can be found at autopsy. Some of these (may be 50%) can be explained by genetic disorders that lead to ion channel dysfunction (“channelopathies”) or other abnormalities in the formation of the action potential.
It is most frequently caused by ventricular tachyarrhythmias: Monomorphic and polymorphic ventricular tachycardia (VT), torsade de pointes (TdP), and ventricular fibrillation (VF). Beta blockade, ACE inhibition, coronary reperfusion and other treatments have reduced the incidence of VT but pulseless electrical activity (PEA) is increasingly seen, particularly in patients with advanced chronic heart disease.
Pulseless electrical activity (PEA) is usually defined as the presence of spontaneous organized cardiac electric activity in the absence of blood flow sufficient to maintain consciousness and (to distinguish it from e.g. vasovagal syncope) absence of a rapid spontaneous return of adequate organ perfusion and consciousness.15 Clinically, PEA is characterized by the absence of a palpable pulse in an unconscious patient with organized electric activity other than ventricular tachyarrhythmia on the ECG.
Older age is associated with PEA and asystole as SCD mechanism.
- Review the clinical manifestations of cardiac arrest
There are usually no symptoms before a cardiac arrest and, without immediate treatment, it will be fatal. If someone is in cardiac arrest:
- they won’t be conscious
- they won’t be responsive
- they won’t be breathing, or breathing normally.
People often think that a cardiac arrest and a heart attack are the same thing, but this isn’t true.
A heart attack happens when blood supplying the heart muscle is cut off due to a clot in one of the coronary arteries. This can cause chest pain, although symptoms can be less severe, and can permanently damage the heart. The heart is still sending blood to the body and the person will be conscious and breathing. A person having a heart attack has a high risk of experiencing a cardiac arrest.
A cardiac arrest occurs when the heart suddenly stops pumping blood around the body, often because of a problem with the electrical signals to the heart muscle. Someone who is having a cardiac arrest will suddenly collapse and will stop breathing.
- Discuss the distinction between supraventricular and ventricular tachycardias
Ventricular tachycardia is a condition in which the SA node no longer controls the beating of the ventricles. Instead, other areas along the lower electrical pathway take over the pacemaking role. Since the new signal does not move through your heart muscle along the regular route, the heart muscle does not beat normally. Your heartbeat quickens, and you feel as if your heart is “skipping beats.” This rhythm may cause severe shortness of breath, dizziness, or fainting (syncope).
Supraventricular Tachycardia (SVT) or Paroxysmal Supraventricular Tachycardia (PSVT)
Supraventricular tachycardia (SVT) is a rapid, regular heart rate where the heart beats anywhere from 150-250 times per minute in the atria. Another name for SVT is paroxysmal supraventricular tachycardia (PSVT). The word “paroxysmal” means occasionally or from time to time.
Supraventricular tachycardia or PVST happens when electrical signals in the heart’s upper chambers fire abnormally, which interferes with electrical signals coming from the SA node (the heart’s natural pacemaker). The beats in the atria then speed up the heart rate.
This type of arrhythmia is more common in infants and young people. It is also more likely to occur in women, anxious young people, and people who are extremely tired (fatigued). People who drink a lot of coffee or alcohol or who are heavy smokers also have a greater risk.
- Discuss the significance of sustained VT in the presence of structural heart disease
DEF: Sustained ventricular tachycardia (VT) is a ventricular rhythm faster than 100 bpm lasting at least 30 seconds or requiring termination earlier due to hemodynamic instability. VT is defined as a wide complex tachycardia (QRS 120 milliseconds or greater) that originates from one of the ventricles, and is not due to aberrant conduction (e.g., from bundle branch block), at a rate of 100 bpm or greater.
Ventricular arrhythmias are responsible for the majority of sudden cardiac deaths (SCD), particularly in patients with structural heart disease. Coronary artery disease, essentially previous myocardial infarction, is the most common heart disease upon which sustained ventricular tachycardia (VT) occurs, being reentry the predominant mechanism. Other cardiac conditions, such as idiopathic dilated cardiomyopathy, Chagas disease, sarcoidosis, arrhythmogenic cardiomyopathies, and repaired congenital heart disease may also present with VT in follow-up. Analysis of the 12-lead electrocardiogram (ECG) is essential for diagnosis. There are numerous electrocardiographic criteria that suggest VT with good specificity. The ECG also guides us in locating the site of origin of the arrhythmia and the presence of underlying heart disease.
The electrophysiological study provides valuable information to establish the mechanism of the arrhythmia and guide the ablation procedure, as well as to confirm the diagnosis when dubious ECG.
Therapy: Given the poor efficacy of antiarrhythmic drug therapy, adjunctive catheter ablation contributes to reduce the frequency of VT episodes and the number of shocks in patients implanted with a cardioverter-defibrillator (ICD). ICD therapy has proven to be effective in patients with aborted SCD or sustained VT in the presence of structural heart disease. It is the only therapy that improves survival in this patient population and its implantation is unquestioned nowadays.
- Discuss the elements of basic life support
- Circulation: providing an adequate blood supply to tissue, especially critical organs, so as to deliver oxygen to all cells and remove metabolic waste, via the perfusion of blood throughout the body.
- Airway: the protection and maintenance of a clear passageway for gases (principally oxygen and carbon dioxide) to pass between the lungs and the atmosphere.
- Breathing: inflation and deflation of the lungs (respiration) via the airway
These goals are codified in mnemonics such as ABC and CAB. The American Heart Association (AHA) endorses CAB in order to emphasize the primary importance of chest compressions in cardiopulmonary resuscitation.
Healthy people maintain the CABs by themselves. In an emergency situation, due to illness (medical emergency) or trauma, BLS helps the patient ensure his or her own CABs, or assists in maintaining for the patient who is unable to do so. For airways, this will include manually opening the patients airway (Head tilt/Chin lift or jaw thrust) or possible insertion of oral (Oropharyngeal airway) or nasal (Nasopharyngeal airway) adjuncts, to keep the airway unblocked (patent). For breathing, this may include artificial respiration, often assisted by emergency oxygen. For circulation, this may include bleeding control or cardiopulmonary resuscitation (CPR) techniques to manually stimulate the heart and assist its pumping action.
- Describe protocols for circulatory support
After nearly 50 years of clinical development, durable mechanical circulatory support (MCS) devices are widely available for patients with advanced heart failure. The field of circulatory support has matured dramatically in recent years, thanks to the advent of smaller, rotary pumps. The resulting transition away from older pulsatile devices has been swift. Accelerated use of continuous-flow left ventricular assist devices (LVADs) for long-term support has changed the face of advanced heart failure care. MCS candidate selection, risk stratification, and management strategies are evolving in tandem with new pump technology, producing a shift in the profiles of patients being considered for MCS. Timely referral for MCS evaluation and appropriate implantation now depends on familiarity with recent advances in pump design and clinical outcomes.
- Describe the use of automated external defibrillators
Automated external defibrillators (AEDs) are lightweight, battery-operated, portable devices that are easy to use. Sticky pads with sensors (called electrodes) are attached to the chest of the person who is having sudden cardiac arrest (SCA).
The electrodes send information about the person’s heart rhythm to a computer in the AED. The computer analyzes the heart rhythm to find out whether an electric shock is needed. If a shock is needed, the AED uses voice prompts to tell you when to give the shock, and the electrodes deliver it.
Using an AED to shock the heart within minutes of the start of SCA may restore a normal heart rhythm. Every minute counts. Each minute of SCA leads to a 10 percent reduction in survival.
Training To Use an Automated External Defibrillator
Learning how to use an AED and taking a CPR (cardiopulmonary resuscitation) course are helpful. However, if trained personnel aren’t available, untrained people also can use an AED to help save someone’s life.
Some people are afraid to use an AED to help save someone’s life. They’re worried that something might go wrong and that they might be sued. However, Good Samaritan laws in each State and the Federal Cardiac Arrest Survival Act (CASA) provide some protection for untrained bystanders who respond to emergencies.
Facility owners who are thinking about buying an AED should provide initial and ongoing training to likely rescuers (usually people who work in the facility). Also, it’s important to properly maintain an AED and notify local emergency officials of its location.
- Describe the elements of advanced cardiac life support
The ACLS Course is designed for healthcare providers who either direct or participate in the resuscitation of a patient whether in or out of hospital. ACLS is based on simulated clinical scenarios that encourage active, hands on participation through learning stations where students will practice essential skills individually, as part of a team, and as team leader.
Realistic simulations reinforce the following key concepts:
proficiency in basic life support care; recognising and initiating early management of peri arrest conditions; managing cardiac arrest; identifying and treating ischemic chest pain and acute coronary syndromes; recognising other life threatening clinical situations (such as stroke) and providing initial care; ACLS algorithms; and effective resuscitation team dynamics. The ACLS course is available in a number of different formats.
- Describe the approach to tachyarrhythmic cardiac arrest
Tachyarrhythmias, defined as abnormal heart rhythms with a ventricular rate of 100 or more beats per minute, are frequently symptomatic and often result in patients seeking care at their provider’s office or the emergency department.
In anyone who presents with a symptomatic tachyarrhythmia, a 12-lead electrocardiogram (ECG) should be obtained while a brief initial assessment of the patient’s overall clinical assessment is performed. If the patient is hemodynamically unstable, it may be preferable to obtain only a rhythm strip prior to urgent cardioversion and not wait for a 12-lead ECG. The information acquired from these initial assessments is crucial for subsequent management of the patient.
Is the patient clinically (or hemodynamically) unstable? — The most important clinical determination in a patient presenting with a tachyarrhythmia is whether or not the patient is experiencing signs and symptoms related to the rapid heart rate. These can include hypotension, shortness of breath, chest pain suggestive of coronary ischemia, shock, and/or decreased level of consciousness.
Determining whether a patient’s symptoms are related to the tachycardia depends upon several factors, including age and the presence of underlying cardiac disease.
Hemodynamically unstable and not sinus rhythm – If a patient has clinically significant hemodynamic instability potentially due to the tachyarrhythmia, an attempt should be made as quickly as possible to determine whether the rhythm is sinus tachycardia (algorithm 1). If the rhythm is not sinus tachycardia, or if there is any doubt that the rhythm is sinus tachycardia, urgent conversion to sinus rhythm is recommended. (See “Clinical manifestations, diagnosis, and evaluation of narrow QRS complex tachycardias”, section on ‘Similar to sinus rhythm’ and “Basic principles and technique of external electrical cardioversion and defibrillation” and “Wide QRS complex tachycardias: Approach to the diagnosis”, section on ‘Assessment of hemodynamic stability’.)
●Hemodynamically stable – If the patient is not experiencing hemodynamic instability, a nonemergent approach to the diagnosis of the patient’s rhythm can be undertaken [1,2]. A close examination of the 12-lead ECG should permit the correct identification of the arrhythmia in 80 percent of cases . (See ‘Is the QRS complex narrow or wide? Regular or irregular?’ below and “Clinical manifestations, diagnosis, and evaluation of narrow QRS complex tachycardias”, section on ‘Evaluation’ and “Wide QRS complex tachycardias: Approach to the diagnosis”, section on ‘Evaluation of the electrocardiogram’.)
Is the QRS complex narrow or wide? Regular or irregular? — Treatment of any tachyarrhythmia depends on a variety of clinical factors. However, most treatment decisions are made based on the width, morphology, and regularity of the QRS complex (algorithm 2). In most patients, the differentiation between narrow and wide QRS complex tachyarrhythmias requires only a surface ECG.
- Discuss pharmacotherapy for resistant arrhythmias
The need for treatment of arrhythmias depends on the symptoms and the seriousness of the arrhythmia. Treatment is directed at causes. If necessary, direct antiarrhythmic therapy, including antiarrhythmic drugs, cardioversion-defibrillation, implantable cardioverter-defibrillators (ICDs), pacemakers (and a special form of pacing, cardiac resynchronization therapy), catheter ablation, surgery, or a combination, is used.
Most antiarrhythmic drugs are grouped into 4 main classes (Vaughan Williams classification) based on their dominant cellular electrophysiologic effect (see Table: Antiarrhythmic Drugs (Vaughan Williams Classification)).
Class I: Class I drugs are subdivided into subclasses a, b, and c. Class I drugs are sodium channel blockers (membrane-stabilizing drugs) that block fast sodium channels, slowing conduction in fast-channel tissues (working atrial and ventricular myocytes, His-Purkinje system).
Class II: Class II drugs are beta-blockers, which affect predominantly slow-channel tissues (sinoatrial [SA] and atrioventricular [AV] nodes), where they decrease rate of automaticity, slow conduction velocity, and prolong refractoriness.
Class III: Class III drugs are primarily potassium channel blockers, which prolong action potential duration and refractoriness in slow- and fast-channel tissues.
Class IV: Class IV drugs are the nondihydropyridine calcium channel blockers, which depress calcium-dependent action potentials in slow-channel tissues and thus decrease the rate of automaticity, slow conduction velocity, and prolong refractoriness.
Digoxin and adenosine are not included in the Vaughan Williams classification. Digoxin shortens atrial and ventricular refractory periods and is vagotonic, thereby prolonging AV nodal conduction and AV nodal refractory periods. Adenosine slows or blocks AV nodal conduction and can terminate tachyarrhythmias that rely upon AV nodal conduction for their perpetuation.
- Describe the approach to asystole, bradyarrhythmias, and pulse-less electrical activity, noting the central role of cardiopulmonary resuscitation
- Describe post-resuscitation care
Successful return of spontaneous circulation (ROSC) is the first step towards the goal of complete recovery from cardiac arrest. The complex pathophysiological processes that occur following whole body ischaemia during cardiac arrest and the subsequent reperfusion response during CPR and following successful resuscitation have been termed the post-cardiac arrest syndrome.4 Depending on the cause of the arrest, and the severity of the post-cardiac arrest syndrome, many patients will require multiple organ support and the treatment they receive during this post-resuscitation period influences significantly the overall outcome and particularly the quality of neurological recovery. The post-resuscitation phase starts at the location where ROSC is achieved but, once stabilised, the patient is transferred to the most appropriate high-care area (e.g. emergency room, cardiac catheterisation laboratory or intensive care unit (ICU)) for continued diagnosis, monitoring and treatment. The post-resuscitation care algorithm (Figure 1) outlines some of the key interventions required to optimise outcome for these patients.
Of those comatose patients admitted to ICUs after cardiac arrest, as many as 40–50% survive to be discharged from hospital depending on the cause of arrest, system and quality of care. Of the patients who survive to hospital discharge, the vast majority have a good neurological outcome although many have subtle cognitive impairment.5-8
- Discuss prognosis
Prognosis involves consideration of:
- the underlying cause of cardiac arrest (e.g. overdose vs dilated cardiomyopathy)
- presence of co-morbidities (e.g. metastatic cancer, dementia)
- use of targeted temperature management (therapeutic hypothermia)
- features of the the cardiac arrest and cardiovascular assessment
- neurological assessment
A 71-year-old male with a history of hypertension, diabetes mellitus, and hyperlipidemia presents to the ED with a first episode of palpitations, shortness of breath, and chest discomfort. The symptoms began without provocation and have been present for almost 3 h. On physical examination, there is an irregularly irregular radial pulse and a heart rate of 90-110 beats per minute. The blood pressure is 112/70 mmHg and the respiratory rate is 20 breaths per minute. A 12-lead ECG shows an irregular wavy baseline produced by rapid fibrillary waves, and a ventricular (QRS) rate that is very irregular. There are no discrete P waves seen.
- Distinguish between atrial flutter and atrial fibrillation (AF)
Atrial flutter is an abnormal cardiac rhythm characterized by rapid, regular atrial depolarizations at a characteristic rate of approximately 300 beats/min and a regular ventricular rate of about 150 beats/min. (See ‘Introduction’ above and ‘Electrophysiologic classification’ above.)
●Atrial flutter is unusual in patients without heart disease. It is often associated with mitral valvular heart disease, post-cardiac surgery, pericardial disease including pericardiotomy, prior heart surgery, and acute or chronic pulmonary diseases. (See ‘Etiology and risk factors’ above.)
●Distinguishing typical from atypical atrial flutter has useful treatment implications, particularly the high success rate of catheter ablation in typical atrial flutter.
●The clinical manifestations are similar to those of atrial fibrillation. (See ‘Clinical manifestations’ above.)
●The diagnosis can usually be made from a 12 lead electrocardiogram. (See ‘Electrocardiogram’ above and ‘Diagnosis’ above.)
●The management of rate-control and anticoagulation strategies for prevention of systemic thromboembolism are similar to those used for atrial fibrillation. However, long-term antiarrhythmic medications are infrequently used given the limitations of pharmacologic therapy and high rate of success of ablation for typical atrial flutter. (See ‘General treatment issues’ above.)
Atrial fibrillation (AF) is the most common cardiac arrhythmia.
●The RR intervals follow no repetitive pattern. They have been labeled as “irregularly irregular.”
●While electrical activity suggestive of P waves is seen in some leads, there are no distinct P waves. Thus, even when an atrial cycle length (the interval between two atrial activations or the P-P interval) can be defined, it is not regular and often less than 200 milliseconds (translating to an atrial rate greater than 300 beats per minute).
AF can have adverse consequences related to a reduction in cardiac output and to atrial and atrial appendage thrombus formation [1-4]. In addition, affected patients may be at increased risk for mortality. (See ‘Long-term outcome’ below.)
AF is more prevalent in men and with increasing age (figure 1) . .
- List conditions most frequently associated with AF
Atrial fibrillation is in most patients (approximately 70%) associated with chronic organic heart disease including valvular heart disease, coronary artery disease, hypertension, particularly if left ventricular hypertrophy is present, hypertrophic cardiomyopathy, dilated cardiomyopathy and congenital heart disease and most commonly in adults, atrial septal defect.
As in many chronic conditions, determining whether AF is the result or is unrelated to the underlying heart disease, remains unclear.
The list of possible etiologies also include cardiac amyloidosis, hemochromatosis and endomyocardial fibrosis. Other heart diseases, such as mitral valve prolapse (with or without mitral regurgitation), calcification of the mitral annulus, atrial myxoma, pheochomocytoma and idiopathic dilated right atrium, present a higher incidence of AF.
The relationship between these findings and the arrhythmia are still unclear. Atrial fibrillation may occur in the absence of detectable organic heart disease, the so-called “lone AF”, in about 30% of cases.
- Describe the loss of the atrial contribution (atrial kick) to ventricular filling
Atrial kick describes the part of the cardiac cycle during which the atrial systole occurs. The atrial systole occurs at the end of the ventricular diastole by the depolarization of the atrial muscle cells which causes the P wave of the electrocardiogram. This depolarization results in atrial contraction, increase in atrial pressure and the transfer of blood from atrium to the ventricle, thus completing the period of ventricular filling.
Atrial kick can be better explained when described as a part of the cardiac cycle. By convention, the cardiac cycle begins at end diastole. Systole can be divided into 2 phases, isovolumetric contraction, and the ejection phase. At end diastole the left ventricular (LV) systole begins, and LV contraction leads to increase in pressure with no change in the LV volume (isovolumetric phase). Once the LV pressure exceeds the aortic pressure, the aortic valve opens leading to the ejection phase of the systole which terminates with the emptying of the LV and the closure of the aortic valve; this marks the beginning of the diastole.
- Explain the increased risk of thromboembolism associated with AF
Atrial fibrillation (AF) and venous thromboembolism (VTE) are the two most common medical conditions managed with anti-coagulation therapy. Not all the patients with decreased mobility or AF have a similar risk for thromboembolism. The risk factors for venous thromboembolism and thromboembolism associated with AF are described in various studies. Considering that the two conditions have similar pathophysiologic basis of clot formation, one could imply that the risk factors for the occurrence of thrombosis could be similar.
AF and VTE are two common medical conditions associated with significant morbidity and mortality. They share a similar pathophysiology for the development of thrombus and management with anticoagulants. The CHADS-VASc risk factors have been well validated in assessing the risk of thromboembolism associated with AF. Considering the similarities of AF and VTE, these factors may have a role in risk assessment of VTE. Though risk factors including age, CHF, diabetes, stroke and peripheral vascular disease predispose to the development of both conditions; factors including hypertension and sex have differential association with the two conditions.
- Briefly describe protocols to achieve rate control in AF without hypotension using beta-blockers or calcium channel blockers
SUMMARY AND RECOMMENDATIONS — The following summary and recommendations are in general agreement with the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society AF guideline [45,46].
This discussion applies to AF patients in whom a chronic rate control strategy has been chosen, or to any AF patient requiring acute rate control.
●In patients without significant heart failure or hypotension, we suggest intravenous beta blockers or nondihydropyridine calcium channel blockers (Grade 2B). (See ‘Acute control with beta blockers’ above and ‘Acute control with calcium channel blockers’ above.)
●Intravenous diltiazem, using the regimen described above, is our preferred drug in this setting. (See ‘Acute control with calcium channel blockers’ above.) However, comparative data are limited and intravenous verapamil or intravenous beta blockers such as metoprolol, propranolol, or esmolol are reasonable alternatives (see ‘Comparative efficacy’ above) .
●If it is uncertain whether such therapy will be tolerated by the patient, esmolol may be cautiously administered since its very short half-life permits a therapeutic trial to be performed at reduced risk. (See ‘Acute control with beta blockers’ above.)
●In patients who do not adequately respond to initial therapy with either an intravenous beta blocker or intravenous calcium channel blocker, we suggest the addition of intravenous digoxin as the second drug in combination therapy (Grade 2C). (See ‘Digoxin’ above.) Some patients have a greater degree of rate control with a beta blocker than with a calcium channel blocker, and vice versa. Thus, in patients who have an inadequate response to one of these drugs, switching to a drug from the other class is an alternative to adding digoxin.
If rate control is achieved, we try to use the second drug as a single agent and to avoid using beta blockers and calcium channel blockers as combination therapy for rate control. However, in selected patients who do not have hypotension or significant left ventricular dysfunction, these classes may be used together, and in some cases all three agents (ie, a beta blocker, a calcium channel blocker, and digoxin) may be necessary to achieve adequate rate control.
●In patients who do not respond to or are intolerant of intravenous calcium channel blockers, beta blockers, and/or digoxin, we suggest intravenous amiodarone for acute control of the ventricular rate (Grade 2C). (See ‘Amiodarone’ above.) In such patients, the use of amiodarone for rate control is a short-term strategy (eg, hours to days). The drug should not be used if pre-excitation is present.
Chronic rate control — Using drugs that block atrioventricular (AV) conduction, at least 75 percent of AF patients can achieve a rate control target of ≤80 beats/min and over 90 percent a target of ≤110 beats/min. However, achieving this goal requires close monitoring, medication adjustments, and often combination therapy. In such patients, adjustments can often be made in the outpatient setting. All rates discussed here are average rates. (See ‘Urgency of therapy’ above and ‘Long-term rate control goals’ above.)
Although there are differences in the efficacy of the various drugs used for rate control, it is likely that monitoring and adjustments to therapy are more important components of successful rate control strategies than is the initial drug selection (algorithm 1).
●We suggest a rate control goal of <85 beats/min, for symptomatic patients in AF in whom a rate control strategy has been chosen (Grade 2C). For patients who continue with unacceptable symptoms at this goal, an attempt should be made to see if a lower rate goal lessens symptoms. (See ‘Long-term rate control goals’ above.) For asymptomatic patients with permanent AF, a more lenient rate control goal of <110 beats/min may be reasonable, as long as patients do not develop LV dysfunction. Careful monitoring for symptoms and/or development of LV dysfunction is imperative.
●In patients who require chronic rate control therapy, we suggest initial therapy with an oral beta blocker or nondihydropyridine calcium channel blockers (Grade 1B). (See ‘Chronic beta blocker therapy’ above and ‘Chronic calcium channel blocker therapy’ above.)
•Beta blockers are preferred in patients with coronary heart disease, heart failure due to systolic dysfunction, and in patients in whom the ventricular rate increases inappropriately during exercise. In the first two settings, beta blockers improve patient survival. (See “Acute myocardial infarction: Role of beta blocker therapy” and “Use of beta blockers in heart failure with reduced ejection fraction”.)
Despite these advantages, beta blockers are contraindicated or relatively contraindicated in some patients, and others cannot tolerate the side effects. (See “Major side effects of beta blockers”.)
•A nondihydropyridine calcium channel blocker is preferred in patients with chronic lung disease and in patients who do not tolerate a beta blocker. Among the calcium channel blockers, verapamil has a somewhat greater blocking effect on the AV node than diltiazem, and the choice between these drugs is often dictated by side effects. Diltiazem may be preferred in patients with mild heart failure if a beta blocker is contraindicated or not tolerated.
●In patients who do not achieve adequate rate control on maximum-tolerated doses of a beta blocker and non-dihydropyridine calcium channel blocker together, we suggest adding digoxin if atrioventricular nodal ablation, pharmacologic rhythm control, or catheter ablation of AF is not being considered (Grade 2C).
Digoxin levels should be periodically assessed; we attempt to keep the level <0.9 ng/mL.
Careful follow-up for side effects such as bradycardia is imperative. (See ‘Combination therapy’ above.) Some patients will not achieve adequate heart rate control with pharmacologic therapy due to poor response to or intolerance of the medications. In such cases, options include reconsideration of a rhythm control strategy and nonpharmacologic therapies to control the ventricular rate (algorithm 1). These issues are discussed separately. (See “Rhythm control versus rate control in atrial fibrillation” and “Control of ventricular rate in atrial fibrillation: Nonpharmacologic therapy”.)
- Briefly describe the decision to restore and maintain sinus rhythm and the role of cardioversion, either pharmacologic or electrical
therapy for AF consists of empirically tested ion channel
blockers, offered without a real understanding of the pathophysiologic
basis of the disease. It is therefore not surprising
that pharmacological therapies for AF are neither as effective
nor as safe as we would like. In major clinical trails, which
have traditionally based success on absence of symptoms
alone, antiarrhythmic drugs (AADs) prevent recurrent AF in
50% to 65% over short-term follow-up. It is largely due to
frustration from current AADs that studies comparing rate
control with rhythm control were conducted. Although the
debate of rhythm versus rate control continues, it is important
to realize that with either therapy, mortality trends in patients
with AF remained unabated…
Timely cardioversion only makes sense in the context of
appropriate therapies to maintain sinus rhythm. Randomized
trials comparing rhythm and rate control strategies over a
short time frame have consistently failed to demonstrate a
mortality benefit with rhythm control.43– 46 Moreover, the
recently published Atrial Fibrillation and Congestive Heart
Failure (AF-CHF) trial showed that an initial strategy of
rhythm control was not superior to rate control even in
patients with heart failure, in whom the theoretical benefit of
rhythm control would seem to be higher.47 In contrast, the
Danish Investigations of Arrhythmia and Mortality on Dofetilide
(DIAMOND) studies, a series of trials assessing the
efficacy and safety of dofetilide to treat AF, showed that
patients who maintained sinus rhythm, either with or without
AADs, had a superior prognosis compared with patients with
- List steps to mitigate clot formation
Only 50% of AFib Patients on Medication to Prevent Stroke
Nearly three million people in the U.S. have atrial fibrillation, and their risk for stroke is five times higher than people without the heart rhythm disorder. That’s because the rapid, irregular heartbeats that define atrial fibrillation can cause blood clots to form, which lead to stroke.
Warfarin (Coumadin), is often prescribed to lower stroke risk in these people because it reduces the blood’s tendency to form clots. This is commonly referred to as “thinning” the blood, explained James Daubert, MD, a heart rhythm specialist at Duke. However, frequent blood tests are needed to determine if the drug is making the blood too thin – which can lead to serious bleeding risks including bleeding in the brain – or too thick, which can cause stroke. Diet is a concern too, as vitamin K, found in green leafy vegetables, inhibits the drug’s effectiveness. These issues make some doctors hesitant to prescribe warfarin, and some people unwilling to take it.
“Only about half of patients with atrial fibrillation who should be on an anticoagulant are on such medications to prevent stroke,” said Daubert.
Safer, More Effective Anticoagulants
Recently, the FDA approved several new stroke-prevention drugs in a new class of drugs called novel oral anticoagulants (NOACs). They’ve proven to be a safer alternative, while doing as good or better job at reducing stroke risk in people with atrial fibrillation. They consistently thin the blood, and there are no dietary restrictions. However, there is currently no way to reverse the effects of the medication, and that makes some doctors cautious about recommending them to their patients.
That’s not the case at Duke, where doctors were the principal investigators of the clinical studies for two of the four new anticoagulants – rivaroxaban (Xarelto) and apixaban (Eliquis). As a result, Daubert explained, “We’re more aggressive about recommending these anticoagulants and more knowledgeable about the real risks and benefits. We have a lot of experience understanding the issues and managing the patients.”
New Devices Prevent Blood Clots from Forming
Two new devices – called left atrial appendage occlusion devices — can protect against stroke in patients unable to safely take anticoagulants long term. The atrium is one of the two areas of the heart where blood collects. “The left atrial appendage is like a little cul de sac off the left atrium,” Daubert explained. “When you are in atrial fibrillation, and the atrium isn’t vigorously contracting, blood can stagnate and form a clot which can cause a stroke.” These devices block the left atrial appendage and prevent clots from escaping.
One device, called the Lariat, uses a lasso-type tip to close-off the neck or opening of the left atrial appendage. It is implanted by an interventional electrophysiologist who inserts catheters through small incisions in the groin and under the breastbone to position the device around the left atrial appendage. Heart rhythm specialist Kevin Jackson, MD, recently performed the first Lariat procedure at Duke.
The second device, called the Watchman, relies on a parachute-type device to block the opening of the left atrial appendage. It was recently approved by the FDA and is only available at a handful of heart centers. Duke was the first North Carolina hospital to implant the device and is now offering it as a treatment option.
“These procedures could help address the risk of stroke in the substantial portion of patients with atrial fibrillation who are either not taking, or are not good candidates, or are at high risk for continual anticoagulation therapy,” Daubert said.
- Review therapies for long-term management of AF
Long-Term Atrial Fibrillation Management
Some patients with atrial fibrillation (AFib, AF) cannot be converted back into sinus rhythm successfully, and every patient who is converted back into sinus rhythm does not necessarily remain in sinus rhythm. In fact, within a year, one-third to one-half of all patients have at least one recurrence of atrial fibrillation. Patients at increased risk of recurrent atrial fibrillation include those whose atria are enlarged (dilated) and those with heart failure.
- Amiodarone (Cordarone)
- Disopyramide (Norpace)
- Dofetilide (Tikosyn)
- Flecainide (Tambocor)
- Procainamide (Procanbid, Pronestyl)
- Propafenone (Rhythmol)
- Quinidine (Quinaglut, Quinidex)
- Sotalol (Betapace)
All of these medications have side effects and many require periodic monitoring.
Reducing Stroke Risk
Patients who are successfully converted from aAFib back into sinus rhythm are considered to be at risk for blood clot formation and stroke for 3 or 4 weeks. Blood-thinning medication is usually administered during this time. Blood thinners may cause bleeding, which may be serious.
Patients who cannot undergo conversion and those who cannot be successfully converted into sinus rhythm are maintained on long-term blood thinning therapy. Typically, this consists of the once-a-day administration of warfarin (Coumadin, Jantoven, generics) or a newer anticoagulant called rivaroxaban. In patients on warfarin, the blood is periodically monitored to insure it is “thinned” to the appropriate degree. Rivaroxaban, which also is taken once daily, doesn’t require the frequent monitoring and dose-adjustment as warfarin.
According to guidelines issued by the American Heart Association, the American College of Cardiology, and the Heart Rhythm Society in 2014, other patients—for example, most women with aFib and people over the age of 65—also may be advised to take blood thinners. In fact, these guidelines suggest that blood thinning medications should be recommended for about 91 percent of all patients with atrial fibrillation and almost 99 percent of people with the condition who are over the age of 65 .
In a select group of patients, aspirin therapy alone provides adequate thinning of the blood. Some patients (particularly those with coronary artery disease) may be treated with warfarin and aspirin.
According to research presented by the American Heart Association in April 2012, some patients with aFib who are on anti-clotting medications and stop taking the drugs are at higher risk for stroke or blood clot within a month. Patients should talk to their doctor if they are instructed to stop taking their medication, for example, because of side effects or an upcoming surgical procedure.
Patients who remain in atrial fibrillation may require long-term therapy with one or more medications that help prevent the heart rate from becoming too rapid. These medications may include beta blockers, calcium channel blockers, and digoxin.
- Beta blockers are used to slow the heart rate. They include:
- Atenolol (Tenormin)
- Bisoprolol (Zebeta)
- Carvedilol (Coreg)
- Metoprolol (Lopressor)
- Toprol XL)
- Nadolol (Corgard)
- Propranolol (Inderal, Inderal LA)
- Timolol (Blockadren)
These medications are usually taken in pill form once or twice a day.
- Calcium channel blockers have multiple effects on the heart and arteries. Two of these agents can be used to slow the heart rate in patients with atrial fibrillation. These medications include diltiazem (Cardizem) and verapamil (Calan, Calan SR, Covera HS, Isoptin, Isoptin SR, Veralan). Long-acting forms of these medications are available that are taken once or twice a day.
- Digoxin (Lanoxin) is often used in the treatment of patients with heart failure, because it can stimulate the left ventricle to contract and pump blood more vigorously. Digoxin also slows electrical conduction through the AV node, and can decrease the rate at which electrical impulses are conducted from the atria down into the ventricles.
- Review the choice of anticoagulants in AF
SUMMARY AND RECOMMENDATIONS
Indications — Anticoagulant therapy is effective in reducing the risk of systemic embolization in patients with nonvalvular atrial fibrillation (AF). Anticoagulation with warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban reduces this risk by almost 70 percent, and should be considered for most nonvalvular AF patients. However, the use of anticoagulant therapy is also associated with an increased risk of major bleeding. While the benefit outweighs the risk in most patients, careful consideration of the risk-to-benefit ratio is necessary in those at relatively very low (CHA2DS2-VASc score of 0) and low risk (CHA2DS2-VASc score of 1). (See ‘Decide on anticoagulation’ above.)
Our recommendations for anticoagulant therapy in patients with nonvalvular AF are as follows (see ‘Decide on anticoagulation’ above):
●For male patients with a CHA2DS2-VASc score of 1 (calculator 1), our authors and reviewers have differing approaches, with some recommending no antithrombotic therapy and some recommending oral anticoagulant therapy. The risk factor present may influence decision making. Age 65 to 74 years is a stronger risk factor than the other features conferring a CHA2DS2-VASc score of 1.
●For patients with a CHA2DS2-VASc of 0 (calculator 1) or 1 in females, we suggest no anticoagulant therapy (Grade 2C). Patients who are particularly stroke averse and who are at low bleeding risk may reasonably choose anticoagulation.
Choice of agent — For those patients who receive antithrombotic therapy, we almost always choose an oral anticoagulant rather than aspirin (or any other antiplatelet regimen). For most patients, we have no confidence that the use of aspirin alone is associated with net clinical benefit. (See ‘Decide on anticoagulation’ above.)
●In patients with nonvalvular AF for whom anticoagulant therapy is chosen, we suggest an oral direct thrombin inhibitor or a factor Xa inhibitor rather than warfarin (Grade 2B). The evidence does not allow for us to prefer one non-vitamin K antagonist oral anticoagulant (NOAC) agent to another. Thus, we suggest that practitioners become familiar with and comfortable using at least one NOAC agent.
Warfarin is a reasonable choice in the following circumstances:
•Patients already on warfarin who are comfortable with periodic international normalized ratio (INR) measurement and whose INR has been relatively easy to control, with an annual time in therapeutic range of at least 65 percent.
•Patients for whom the cost of the non-vitamin k oral antagonist anticoagulants is an important concern.
•Patients with chronic severe kidney disease, whose estimated glomerular filtration rate is less than 30 mL/min/1.73m2 (less than 25 mL/min/1.73m2 for apixaban). (See “Management of thromboembolic risk in patients with atrial fibrillation and chronic kidney disease”, section on ‘Benefits and risks of oral antithrombotic therapy’.)
•Patients for whom NOACs are contraindicated, including those on enzyme-inducing antiepileptic drugs (eg, phenytoin) and patients with human immunodeficiency virus infection (HIV) on protease inhibitor-based antiretroviral therapy.
●For the rare patient who cannot take anticoagulant therapy for reasons other than bleeding risk, we suggest aspirin 75 to 100 mg daily plus clopidogrel 75 mg daily, rather than aspirin alone (Grade 2B). (See ‘Other antiplatelet regimens’ above.)
●Dabigatran, rivaroxaban, apixaban, and edoxaban should not be used in patients with severely impaired renal function (estimated glomerular filtration rate less than 30 mL/min/1.73m2 for dabigatran and rivaroxaban; less than 25 mL/min/1.73m2 for apixaban), those with prosthetic heart valves, those with rheumatic mitral valve disease, mitral stenosis of any origin, or those with other valvular lesions associated with moderate to severe heart failure that might lead to valve replacement in the near future. Edoxaban should also not be prescribed for patients with an estimated glomerular filtration rate of greater than 95 mL/min.
●Our approach to starting warfarin is presented separately (see “Warfarin and other VKAs: Dosing and adverse effects”, section on ‘Initial dosing’)
●For patients prescribed one of the NOACs, we suggest that clinicians review dosing recommendations made by regulatory agencies and available in reputable drug information compendia such as Lexi-Comp. (See ‘Initiate anticoagulant’ above.)
- Discuss the long-term prognosis
In the absence of proven effective therapies for the primary prevention of AF, contemporary AF treatment focuses on thromboembolic risk assessment and risk-appropriate anticoagulation, rhythm control in some symptomatic individuals, and aggressive cardiovascular risk factor modification. The prognosis of patients with AF, particularly the increasing number of individuals with both AF and heart failure, remains poor despite advances in the treatment of AF.52 Further efforts are needed to better understand the longitudinal course of AF among older adults and the long-term prognosis of patients with AF and comorbid cardiovascular diseases and surgeries. It is also clear that the associations between AF and adverse outcomes are stronger in subgroups with comorbidities such as those with heart failure and those who have undergone cardiac surgery than in healthier populations. Future research is needed to determine whether targeting of primary and secondary prevention interventions on such patients, perhaps through the use of prognostic markers, improves prognosis from AF.53,54
A 43-year-old male with a history of injection drug use presents to the ED with a history of several days of dyspnea, occasional fevers, and new-onset syncope. On physical examination, the T is 38.2oC, pulse is 78/min, respiratory rate is 24/min, and blood pressure is 108/70 mmHg. He is ill-appearing and diaphoretic. On auscultation of the heart, there is a grade II/VI systolic murmur at the apex, consistent with tricuspid regurgitation. Three blood cultures are positive for S. aureus.
- Describe infective endocarditis
Infective endocarditis (IE) is defined as an infection of the endocardial surface of the heart (see the image below), which may include one or more heart valves, the mural endocardium, or a septal defect. Its intracardiac effects include severe valvular insufficiency, which may lead to intractable congestive heart failure and myocardial abscesses. If left untreated, IE is almost inevitably fatal.
IE currently can be described as infective endocarditis in the era of intravascular devices, as infection of intravascular lines has been determined to be the primary risk factor for Staphylococcus aureus bloodstream infections (BSIs). S aureus has become the primary pathogen of endocarditis. 
IE generally occurs as a consequence of nonbacterial thrombotic endocarditis, which results from turbulence or trauma to the endothelial surface of the heart. A transient bacteremia then seeds the sterile platelet/fibrin thrombus, with IE as the end result. Pathologic effects due to infection can include local tissue destruction and embolic phenomena. In addition, secondary autoimmune effects, such as immune complex glomerulonephritis and vasculitis, can occur. (See Pathophysiology.)
IE remains a diagnostic and therapeutic challenge. Its manifestations may be muted by the indiscriminate use of antimicrobial agents or by underlying conditions in frail and elderly individuals or immunosuppressed persons.
- Explain why dividing cases between acute and subacute infective endocarditis is no longer considered reliable
Historically, infective endocarditis has been clinically divided into acute and subacute presentations (because untreated patients tended to live longer with the subacute as opposed to the acute form). This classifies both the rate of progression and severity of disease.
- Subacute bacterial endocarditis (SBE) is often due to streptococci of low virulence (mainly viridans streptococci) and mild to moderate illness which progresses slowly over weeks and months (>2 weeks) and has low propensity to hematogenously seed extracardiac sites.
- Acute bacterial endocarditis (ABE) is a fulminant illness over days to weeks (<2 weeks), and is more likely due to Staphylococcus aureus which has much greater virulence, or disease-producing capacity and frequently causes metastatic infection.
This classification is now discouraged because the ascribed associations (in terms of organism and prognosis) were not strong enough to be relied upon clinically. The terms short incubation (meaning less than about six weeks), and long incubation (greater than about six weeks) are preferred.
- Review key epidemiologic points regarding infective endocarditis, and the increase in the rate of endocarditis, especially in injection drug users, caused by aureus
Important changes occurred in IE epidemiology over the last half-century, especially in the last decade. Staphylococcal and enterococcal IE percentage increased while Streptococcus viridans (SV) and culture negative (CN) IE decreased. Moreover, mean age at diagnosis increased together with male:female ratio. These changes should be considered at the time of decision-making in treatment of and prophylaxis for IE.
The reason for the large increase in incidence of SAE related to intravenous drug use noted over time is likely to be multifactorial. An increasing number of PWID probably plays a role. — PWID = Possession with Intent to Distribute (criminal narcotics charge).
- Comment on the association of:mitral valve prolapse with thickened mitral leaflets and Mitral valve prolapse (MVP; a.k.a. floppy mitral valve syndrome, systolic click murmur syndrome or billowing mitral leaflet) is a valvular heart disease characterized by the displacement of an abnormallythickened mitral valve leaflet into the left atrium during systole.prosthetic cardiac valves with infective endocarditis
Infection of an intracardiac prosthesis, the incidence of which is about 2.5% among patients having undergone valve replacement, is a serious complication with considerable morbidity and mortality. Early prosthetic valve endocarditis (PVE), with an onset within 60 days of valve replacement, accounts for approximately one-third of all cases, while the remaining two-thirds, occur more than two months postoperatively (late prosthetic valve endocarditis). Prosthetic valve endocarditis is most commonly caused by Staphylococcus epidermidis, less frequently by viridans streptococci, Staphylococcus aureus, and gram-negative bacilli. The most likely pathogenetic mechanisms in prosthetic valve endocarditis are intraoperative contamination and postoperative infections at extracardiac sites.
ASSOCIATION – ?
- Review the sequence of steps that lead from endocardial damage to invasion of the endocardial surface and metastatic infection
Etiology and Pathophysiology
Endocarditis begins as endothelial damage and sterile surface microthrombus, which, in the absence of bacteremia, regresses or grows into macrothrombi (noninfectious endocarditis).
Malformed stenotic or regurgitant valves
Malformed stenotic valves, or especially regurgitant valves, are predisposed to endocarditis. In the presence of bacteremia or fungemia, even transient or those with low microbe counts, microthrombi become infected, by adhesion and colonization of the thrombotic surfaces. Growth of organisms results in an inflammatory response, with neutrophil infiltration, enlargement of the thrombus, recruitment of matrix metalloproteinases (MMPs), and eventual destruction of collagen and cusp perforation. In approximately 25% of patients, however, neither structural valve abnormalities nor predisposing conditions are evident.
Valve abnormalities, disease, prosthesis, and previous surgery
Congenital valve abnormalities, acquired valve disease, prostheses, and previous cardiac surgery for structural congenital heart disease increase the risk for endocarditis and are indications for antibiotic prophylaxis for dental and other invasive procedures. In nosocomial endocarditis, bacteremic conditions are present in nearly 40% of cases and include intravenous drug abuse, hemodialysis, catheterizations, and intravascular devices. 
The organisms responsible for most cases of infectious endocarditis are gram-positive cocci: streptococci and, increasingly, staphylococci. The most common microbial infection is staphylococcus. Hospital-acquired infection is often associated with hemodialysis, prosthetic valvular infection, malignancies, and vascular interventions.
Some cases of culture-negative endocarditis are caused by fastidious gram-negative organisms of the Haemophilus parainfluenzae, Actinobacillus, Actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae (HACEK) group, which constitutes approximately 1-3% of cases of community-acquired endocarditis on native and prosthetic valves, and may have a relatively good prognosis.
Organisms causing community-acquired endocarditis include the following:
Staphylococcus aureus (30-50%; minority, methicillin-resistant Staphylococcus aureus [MRSA])
Alpha-hemolytic (viridans) streptococci (10-35%)
Culture negative (5-30%)
Fungi (< 5%)
Staphylococcus epidermidis (coagulase negative; < 5%)
Others (eg, Escherichia coli, Klebsiella, Corynebacterium; < 5%)
Organisms responsible for nosocomial endocarditis include the following:
S aureus (60-80%; majority, MRSA)
Alpha-hemolytic streptococci (< 5%)
Culture negative (5%)
S epidermidis (coagulase negative; < 5%)
Others (eg, E coli, Klebsiella, Corynebacterium; 5-10%)
The rate of culture-negative endocarditis varies from 7% to 33% and is increased in community-acquired infections because of antibiotic treatment before diagnosis. No association exists between culture negativity and underlying etiology or risk factors. If a full work-up is performed at a tertiary reference center, including serology and culture for esoteric organisms and polymerase chain reaction (PCR), an etiology is found in over 75% of cases of endocarditis with an initial negative culture. The most common organisms are C burnetii and Bartonella species. 
- Describe various modes of presentation of infective endocarditis
Signs and symptoms
In patients with infective endocarditis (IE), the present illness history is highly variable. Symptoms commonly are vague, emphasizing constitutional complaints, or complaints may focus on primary cardiac effects or secondary embolic phenomena. Fever and chills are the most common symptoms; anorexia, weight loss, malaise, headache, myalgias, night sweats, shortness of breath, cough, or joint pains are common complaints as well.
Fever, possibly low-grade and intermittent, is present in 90% of patients with IE. Heart murmurs are heard in approximately 85% of patients.
One or more classic signs of IE are found in as many as 50% of patients. They include the following:
Petechiae: Common, but nonspecific, finding
Subungual (splinter) hemorrhages: Dark-red, linear lesions in the nail beds
Osler nodes: Tender subcutaneous nodules usually found on the distal pads of the digits
Janeway lesions: Nontender maculae on the palms and soles
Roth spots: Retinal hemorrhages with small, clear centers; rare
Signs of neurologic disease, which occur in as many as 40% of patients, include the following  :
Embolic stroke with focal neurologic deficits: The most common neurologic sign
Other signs of IE include the following:
Paralysis, hemiparesis, aphasia
Pleural friction rub
Subacute native valve endocarditis
The symptoms of early subacute native valve endocarditis (NVE) are usually subtle and nonspecific; they include the following:
Low-grade fever: Absent in 3-15% of patients
Syndromes similar to rheumatic fever, such as fever, dulled sensorium (as in typhoid), headaches
Abdominal symptoms, such as right upper quadrant pain, vomiting, postprandial distress, appendicitis-like symptoms
- List important physical examination and laboratory findings in infective endocarditis, including Osler nodes, Janeway nodes, splinter hemorrhages, and Roth spots
Endocarditis is an endovascular infection associated with the persistent presence of infecting microorganisms in blood. For this reason, blood cultures are the standard test to determine the microbiologic etiology of infective endocarditis. Routine blood cultures incubated on modern automated, continuous-monitoring blood culture systems allow recovery of almost all easily cultivable agents of endocarditis without additional specialized testing, such as prolonged incubation or terminal subculture.
For organisms that do not grow in routine bacterial cultures (e.g., C. burnetii) or are especially fastidious (e.g., Bartonella species), serologic evaluation may aid in diagnosis.
- Review protocols to obtain blood cultures and the Modified Duke Criteria for the diagnosis of infective endocarditis
Standard blood culture incubation times of 5 days are adequate for recovery of almost all cultivable causes of endocarditis, including Candida species. The HACEK organisms were classically considered challenging to detect in blood cultures due to their fastidious nature; accordantly, in the past, prolonged incubation times were advised. With current blood culture systems, extended incubation (and terminal blind subculture) is unnecessary for recovery of these organisms, as they are easily grown and detected within the standard 5-day incubation period (11, 12).
- Summarize important organisms causing infective endocarditis
- Explain why trans-esophageal echocardiography (TEE) is preferred in the evaluation of suspected prosthetic valve or device-related endocarditis
Echocardiography plays a key role in the assessment of infective endocarditis (IE). It is useful for the diagnosis of endocarditis, the assessment of the severity of the disease, the prediction of short- and long-term prognosis, the prediction of embolic events, and the follow-up of patients under specific antibiotic therapy. Echocardiography is also useful for the diagnosis and management of the complications of IE, helping the physician in decision-making, particularly when a surgical therapy is considered. Finally, intraoperative echocardiography must be performed in IE to help the surgeon in the assessment and management of patients with IE during surgery.
In 1994, Durack proposed a new classification of IE (Duke criteria), 11 including, for the first time, echocardiography as a major criterion for IE. The major echographic criteria for IE are vegetation, abscess, and new dehiscence of a prosthetic valve ( Figure 2 ).
The three main echocardiographic criteria for endocarditis (TEE). ( A ) Large vegetation on the anterior mitral leaflet with chordae rupture (arrow). ( B ) Abscess: zone of reduced density (arrow) on the posterior part of the aortic root. ( C ) New prosthetic regurgitation (arrow) affecting a mechanical mitral prosthetic valve. LA, left atrium; LV, left ventricle; RV, right ventricle; Ao, aorta; A, abscess.
- Review antibiotic protocols for infective endocarditis caused by various organisms
- Describe continuing care of the patient with endocarditis
- You may need to continue IV therapy for up to 6 weeks at home. You will be given more instructions before you leave the hospital. Make sure to ask any questions you have. Your healthcare team will determine how long you should be on antibiotics and how often you should have follow up testing.
- Take the antibiotics until they are all gone. Take them even if you feel better. They treat the infection and prevent it from returning.
- Do not drive until your healthcare provider says it’s OK.
- Take good care of your teeth and mouth. Brush your teeth after meals. Floss as directed.
- Visit your dentist every 6 months. Dental infection is a risk factor for bacterial endocarditis. See your dentist immediately if you have a toothache or abscess.
- You might need to take an antibiotic before dental visits. Ask your healthcare provider for more information.
- Tell your healthcare provider about all infections you have, even small ones.
- Take good care of yourself. Get regular exercise and eat a healthy diet. Ask your healthcare provider for help as needed.
- Stop smoking.
- Be careful to get proper treatment of any open cuts that develop.
Make a follow-up appointment as directed by our staff. You will need follow up with an infectious disease doctor as well as a cardiologist and possibly a heart surgeon.
When to call your healthcare provider
Call your healthcare provider right away if you have any of the following:
- Tiredness that persists for 2 to 3 days
- Decreased exercise tolerance
- Chest pain or shortness of breath
- Fever over 100.4°F (38.0°C)
- Severe abdominal or flank pain
- Bloody urine
- Return of symptoms such as loss of appetite, weight loss, paleness, headache, or weakness
- Trouble speaking
- Weakness in any extremity or face
- Spots on your fingernails, fingertips, whites of the eyes, or other parts of your skin
- Symptoms of a stroke such as trouble speaking or inability to move one side of your body.
- Describe complications associated with infective endocarditis
The following are potential complications of IE:
Myocardial infarction, pericarditis, cardiac arrhythmia
Cardiac valvular insufficiency
Congestive heart failure
Sinus of Valsalva aneurysm
Aortic root or myocardial abscesses
Arterial emboli, infarcts, mycotic aneurysms
Glomerulonephritis, acute renal failure
Mesenteric or splenic abscess or infarct 
Congestive heart failure due to aortic valve insufficiency is the most common intracardiac complication of subacute endocarditis. It develops after months of untreated disease but may occur a full year following microbiological cure.
The complication of arterial embolization is second in frequency to congestive heart failure for both subacute and acute IE. The frequency of this complication has decreased, from 80% in the preantibiotic era to 15-35% today. The emboli are usually sterile because of the minimally invasive nature of the causative organisms (eg, S viridans).
The persons most at risk are younger (20-40 y), have mitral or aortic valve (native or prosthetic) involvement, and are infected with certain organisms such as Candida or Aspergillus species, S aureus, Haemophilus parainfluenzae, group B streptococci, and nutritionally variant streptococci.
The prevalence of embolization appears to be the same for both types of disease. The most common areas of deposition include the coronary arteries, kidneys, brain, and spleen. Infarction at the site of embolization is common; abscess formation is not. Cerebral emboli occur in 33% of patients. The middle cerebral artery is involved most often.
Other neurological embolic damage includes cranial nerve palsies, cerebritis, and mycotic aneurysms caused by weakening of the vessel walls and produced by embolization to the vasa vasorum. Mycotic aneurysms may occur in the abdominal aorta and the splenic, coronary, and pulmonary arteries.
In acute IE, the frequency of aneurysms and other suppurative intracardiac complications is high. In addition to valvular insufficiency, other intracardiac complications of acute IE include (1) aortocardiac and other fistulas, (2) aneurysms of the sinus of Valsalva, (3) intraventricular abscesses, (4) ring abscesses, (5) myocardial abscesses, (6) mycotic aneurysms, (7) septic coronary arterial emboli, and (8) pericarditis.
In patients with acute disease, especially disease caused by S aureus infection,emboli almost inevitably lead to abscesses in the areas where they are deposited. Multiple abscesses can occur in almost every organ, including the kidneys, heart, and brain. Mycotic aneurysms may occur in almost any artery. Paradoxically, they are less common in patients with acute IE. [60, 61]
- Explain why some patients may require surgery for endocarditis
The role of surgery in active IE has expanded progressively since early reports of successful outcome.10 Subsequent declines in mortality may be attributed to a variety of improvements in management, although expeditious surgery in carefully selected patients has played a major role. Contemporary data in Europe indicate that surgery is now undertaken in approximately 50% of patients with IE; the most frequent indications are congestive heart failure (60%), refractory sepsis (40%), embolic complications (18%), and vegetation size (48%), with a combination of these factors being present in many patients.11
- Discuss protocols for endocarditis prophylaxis
High-risk cardiac conditions
Antibiotic prophylaxis is indicated for the following high-risk cardiac conditions:
Prosthetic cardiac valve
History of infective endocarditis
Congenital heart disease (CHD) (antibiotic prophylaxis is recommended only for the following forms of CHD [and no others]): (1) unrepaired cyanotic CHD, including palliative shunts and conduits; (2) completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure; and (3) repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibits endothelialization)
Cardiac transplant recipients with cardiac valvular disease
For patients with high cardiac risk, antibiotic prophylaxis is recommended for all dental procedures that involve manipulation of gingival tissue or the periapical region of teeth or perforation of the oral mucosa.
Respiratory tract, infected skin, skin structures, or musculoskeletal tissue procedures
Antibiotic prophylaxis is recommended for invasive respiratory tract procedures that involve incision or biopsy of the respiratory mucosa (eg, tonsillectomy, adenoidectomy). For invasive respiratory tract procedures to treat an established infection (eg, drainage of abscess, empyema), administer an antibiotic that is active against Streptococcus viridans.
Patients with high cardiac risk who undergo a surgical procedure that involves infected skin, skin structure, or musculoskeletal tissue should receive an agent active against staphylococci and beta-hemolytic streptococci (eg, antistaphylococcal penicillin, cephalosporin).
If the causative organism of respiratory, skin, skin structure, or musculoskeletal infection is known or suspected to be Staphylococcus aureus, administer an antistaphylococcal penicillin or cephalosporin, or vancomycin (if patient is unable to tolerate beta-lactam antibiotics). Vancomycin is recommended for known or suspected methicillin-resistant strains of S aureus.
Genitourinary or GI tract procedures
Antibiotics are no longer recommended for endocarditis prophylaxis for patients undergoing genitourinary or gastrointestinal tract procedures.
The most common cause of endocarditis for dental, oral, respiratory tract, or esophageal procedures is S viridans (alpha-hemolytic streptococci). Antibiotic regimens for endocarditis prophylaxis are directed toward S viridans, and the recommended standard prophylactic regimen is a single dose of oral amoxicillin. Amoxicillin, ampicillin, and penicillin V are equally effective in vitro against alpha-hemolytic streptococci; however, amoxicillin is preferred because of superior gastrointestinal absorption that provides higher and more sustained serum levels.
All doses shown below are administered once as a single dose 30-60 minutes before the procedure.
Standard general prophylaxis: Amoxicillin 2 g PO
Unable to take oral medication: Ampicillin 2 g IV/IM
Allergic to penicillin: (1) Clindamycin 600 mg PO or (2) cephalexin 2 g PO or other first- or second-generation oral cephalosporin in equivalent dose (do not use cephalosporins in patients with a history of immediate-type hypersensitivity penicillin allergy, such as urticaria, angioedema, anaphylaxis) or (3) azithromycin or clarithromycin 500 mg PO
- Discuss the prognosis of untreated infective endocarditis
Prognosis largely depends on whether or not complications develop. If left untreated, IE is generally fatal. Early detection and appropriate treatment of this uncommon disease can be lifesaving. The overall mortality rate has remained stable at 14.5%. 
Cure rates for appropriately managed (including both medical and surgical therapies) NVE are as follows:
For S viridans and S bovis infection, the rate is 98%.
For enterococci and S aureus infection in individuals who abuse intravenous drugs, the rate is 90%.
For community-acquired S aureus infection in individuals who do not abuse intravenous drugs, the rate is 60-70%.
For infection with aerobic gram-negative organisms, the rate is 40-60%.
For infection with fungal organisms, the rate is lower than 50%.
For PVE, the cure rates are as follows:
Rates are 10-15% lower for each of the above categories, for both early and late PVE.
Surgery is required far more frequently.
Approximately 60% of early CoNS PVE cases and 70% of late CoNS PVE cases are curable.
A 12-year-old female Pacific Islander presents with a 2-day history of fever and hot, red, swollen, and very tender joints. On questioning, she reveals that she had a sore throat 3 weeks ago, but did not seek medical help (she did not tell her parents). Her current illness began with fever and a sore and swollen right knee that was quite painful. The following day her right knee was improved, but her left elbow became sore and swollen. While in the waiting room her left knee became painful and swollen.
- Review the evidence linking antecedent group A streptococcal upper pharyngitis tract infection and acute rheumatic fever and rheumatic heart disease
For many years, it has been established dogma that ARF only follows upper respiratory tract infection with group A streptococci (GAS), in contrast to poststreptococcal acute glomerulonephritis (AGN), which may follow GAS infection of either the throat or skin. This dogma is based on an accumulated body of epidemiologic evidence relating to both primary and recurrent episodes of rheumatic fever. Among such evidence are observations from both civilian and military populations in which ARF followed epidemics of pharyngitis and/or scarlet fever caused by strains of a limited number of “rheumatogenic” GAS M protein types. Moreover, ARF incidence has not been found to increase during epidemics of pyoderma-associated AGN.
- Discuss the importance of crowding in facilitating the spread of group A streptococcal infections and outbreaks of acute rheumatic fever
- Discuss the concept of rheumatogenicity and the importance of serotypes of group A streptococci (M types 1, 3, 5, 6, 18, and 29)
- Discuss the sharp decline in the incidence of acute rheumatic fever in industrialized countries, while it remains high in ethnic minority populations within Australia and New Zealand
- Discuss the molecular mimicry hypothesis for immune-mediated pathogenesis of acute rheumatic fever and rheumatic heart disease
- Review updated Jones criteria
In the final Jones criteria, different diagnostic criteria were established for the diagnosis of acute rheumatic fever for low risk and moderate-high risk populations. Turkey was found to be compatible with moderate-high risk populations as a result of regional screenings performed in terms of acute rheumatic fever and rheumatic heart disease. The changes in the diagnostic criteria for low-risk populations include subclinical carditis found on echocardiogram as a major criterion in addition to carditis found clinically and a body temperature of 38.5°C and above as a minor criterion. In moderate-high risk populations including Turkey, subclinical carditis found on echocardiogram in addition to clinical carditis is used as a major criterion as a new amendment. In addition, aseptic monoarthritis and polyarthralgia are used as major criteria in addition to migratory arthritis and monoarhtralgia is used as a minor criterion among joint findings.
However, differentiation of subclinical carditis from physiological valve regurgitation found in healthy individuals and exclusion of other diseases involving joints when aseptic monoarthritis and polyarthralgia are used as major criteria are very important. In addition, a body temperature of 38°C and above and an erythrocyte sedimentation rate of 30 mm/h and above have been accepted as minor criteria.
The diagnostic criteria for the first attack have not been changed; three minor findings have been accepted in presence of previous sterptococcal infection in addition to the old cirteria for recurrent attacks. In the final Jones criteria, it has been recommended that patients who do not fully meet the diagnostic criteria of acute rheumatic fever should be treated as acute rheumatic fever if another diagnosis is not considered and should be followed up with benzathine penicilin prophylaxis for 12 months. It has been decided that these patients be evaluated 12 months later and a decision for continuation or discontinuation of prophylaxis should be made. In countries where the disease is prevalent, it is very important for physicians to make an accurate diagnosis of acute rheumatic fever with their own logic and assessment in addition to the criteria proposed.
- List the major criteria and describe the migratory nature of the polyarthritis and the dramatic response to even low doses of salicylates of the arthritis of acute rheumatic fever
Migratory polyarthritis is defined as the kind of arthritis that affects many joints progressively. It is usually observed in people suffering from gonorrhea. This kind of arthritis usually affects the larger joints and begins in an order starting from ankle, knee, wrist, elbow, shoulder and hip. The inflammation is felt in the wrist and after a flare-up it travels to the other part of body and inflames those joints, thus the name ‘migratory polyarthritis’.
- Rheumatic Fever:- When a streptococcal bacterial infection such as scarlet fever or strep throat is left untreated, it gives rise to complications and an inflammatory disorder known as rheumatic fever. The infection causes the immune system to become alert and launch an attack that even harms the healthy tissues. This causes inflammation of the joints and in severe cases, it even damages the heart.
How salicylates work: These drugs decrease the production of prostaglandins. Prostaglandins are substances found in many tissues. They cause pain and inflammation. The use of salicylates for rheumatoid arthritis has been largely replaced by nonsteroidal anti-inflammatory drugs.
- Discuss the endocarditis of rheumatic carditis
- Describe various clinical manifestations of Sydenham chorea
- Describe erythema marginatum
Erythema marginatum is a type of erythema (redness of the skin or mucous membranes) involving pink rings on the torso and inner surfaces of the limbs which come and go for as long as several months. It is found primarily on extensor surfaces.
- Describe subcutaneous nodules
It is assumed that subcutaneous nodule (SCN), one of the major criteria in acute rheumatic fever (ARF), is rare and whenever these nodules appear, they are invariably associated with carditis. Further large number of nodules appear in crops and they are evanescent.
Subcutaneous nodules have been reported in <1% to 21% of the cases. They rarely occur as an isolated manifestation, and they are associated with carditis in most cases.
For example …in an 8-year-old child with a fever for the preceding 45 days, migratory polyarthralgia involving large joints, and progressively worsening dyspnea on exertion. …subcutaneous nodules over the bony prominences of the spine, scapulae, forehead, extensor surfaces of bilateral elbow joints and knee joints, ankles, and the rib cage
- Describe the importance of elevated levels of titers of antistreptolysin O, anti-DNase B, and anti-hyaluronidase in establishing a recent infection with group A streptococci
- Review the differential diagnosis of rheumatic fever
- Describe antibiotic therapy and anti-inflammatory therapy
Penicillin G benzathine
Patients weighing 27 kg (60 lb) or less: 600,000 units IM every 4 weeks†
Patients weighing more than 27 kg: 1,200,000 units IM every 4 weeks†
Penicillin V potassium
250 mg orally twice daily
Patients weighing 27 kg or less: 0.5 g orally once daily
Patients weighing more than 27 kg: 1 g orally once daily
Macrolide or azalide antibiotic (for patients allergic to penicillin and sulfadiazine)‡
- Discuss the prognosis of acute rheumatic fever
With treatment, it can resolve within two weeks. The ultimate prognosis, however, is determined by the level of heart involvement with rheumatic fever. … Because of this risk, most patients who have had one bout episode of rheumatic fever will be placed on long-term antibiotics to prevent another strep infection.
- Discuss primary and secondary prevention of group A streptococcal infection
Primary prevention aims to prevent complications from a known problem. In Australia, primary prevention includes early diagnosis of group A streptococcus throat infections in people most at risk of ARF (typically children aged 5–14 years), and treatment with antibiotics, commonly penicillin. This helps prevent spread of the streptococcal infection to others and helps prevent the infected person’s body having an auto-immune reaction to the infection resulting in ARF.
Secondary Prevention refers to the early detection of disease and measures to prevent recurrent disease and worsening of the condition. This means preventing recurrent ARF which in turn prevents RHD or stops existing RHD worsening. Secondary prophylaxis with regular benzathine penicillin G (BPG) is the only RHD control strategy shown to be effective and cost-effective at both community and population levels. Secondary prevention should also include strategies aimed at improving the delivery of secondary prophylaxis and patient care, the provision of education, coordination of available health services and advocacy for necessary and appropriate resources.
- Discuss the duration of prophylaxis for people who have had acute rheumatic fever
Continuous prophylaxis is recommended in patients with well-documented histories of rheumatic fever and in those with evidence of rheumatic heart disease (Tables 3 and 4). Prophylaxis should be initiated as soon as acute rheumatic fever or rheumatic heart disease is diagnosed. To eradicate residual GAS, a full course of penicillin should be given to patients with acute rheumatic fever, even if a throat culture is negative.
Penicillin G benzathine
Patients weighing 27 kg (60 lb) or less: 600,000 units IM every 4 weeks†
Patients weighing more than 27 kg: 1,200,000 units IM every 4 weeks†
Penicillin V potassium
250 mg orally twice daily
Patients weighing 27 kg or less: 0.5 g orally once daily
Patients weighing more than 27 kg: 1 g orally once daily
Macrolide or azalide antibiotic (for patients allergic to penicillin and sulfadiazine)‡
Rheumatic fever with carditis and residual heart disease (persistent valvular disease†)
10 years or until age 40 years (whichever is longer); lifetime prophylaxis may be needed
Rheumatic fever with carditis but no residual heart disease (no valvular disease†)
10 years or until age 21 years (whichever is longer)
Rheumatic fever without carditis
5 years or until age 21 years (whichever is longer)